СПОСОБ СИНТЕЗА КОНЪЮГАТОВ ГЛИКОЗАМИНОГЛИКАНОВ (GAG) С БИОЛОГИЧЕСКИ АКТИВНЫМИ МОЛЕКУЛАМИ, ПОЛИМЕРНЫЕ КОНЪЮГАТЫ И ИХ СООТВЕТСТВУЮЩИЕ ПРИМЕНЕНИЯ

Изобретение относится к медицине. Описан способ синтеза конъюгатов гликозаминогликанов (GAG) с биологически активными молекулами различной природы, включающими низкомолекулярные соединения и макромолекулы. Конкретно, изобретение относится к конъюгации гиалуроновой кислоты (HA) и ее производных с полипептидами и белками с биологической функцией, такими как, например, интерфероны, эритропоэтины, факторы роста, инсулин, цитокины, антитела и гормоны. Изобретение позволяет выделять промежуточные соединения, полученные с помощью частичного или полного взаимодействия GAG с защищенными аминоальдегидами в способе конъюгации. Конъюгаты способны повышать эффективность конъюгированного лекарственного средства и поддерживать ее в течение времени. 6 н. и 19 з.п. ф-лы, 13 ил., 15 пр.

СПОСОБ ДЕАЦЕТИЛИРОВАНИЯ БИОПОЛИМЕРОВ

Изобретение относится к химии биополимеров. Предложенный способ для по меньшей мере частичного деацетилирования гликозаминогликана, содержащего ацетильные группы, включает обеспечение гликозаминогликана, содержащего ацетильные группы и имеющего средневесовую молекулярную массу в диапазоне от 1 до 5 МДа. Затем проводят реакцию гликозаминогликана, содержащего ацетильные группы, с гидроксиламином (NH2OH) или его солью при температуре 10-90°C в течение 2-200 ч с образованием по меньшей мере частично деацетилированного гликозаминогликана. После чего выделяют по меньшей мере частично деацетилированный гликозаминогликан. Полученный указанным способом гликозаминогликан характеризуется степенью ацетилирования 99% или менее и средневесовой молекулярной массой 0,5 МДа или более. Также предложены применение гидроксиламина или его соли для по меньшей мере частичного деацетилирования гликозаминогликана и способ получения гидрогелевого продукта. Изобретение направлено на деацетилирование биополимеров, ...

УГЛЕВОДНЫЙ СШИВАЮЩИЙ АГЕНТ

ПРОИЗВОДНЫЕ СУЛЬФАТИРОВАННЫХ ПОЛИСАХАРИДОВ, ИХ СПОСОБ ПОЛУЧЕНИЯ, МОДИФИКАЦИЯ И ПРИМЕНЕНИЕ

СПОСОБ СШИВАНИЯ ПОЛИСАХАРИДОВ ПРИ ПОМОЩИ ФОТОУДАЛЯЕМЫХ ЗАЩИТНЫХ ГРУПП

Verwendung von desulfatiertem Heparin

Zusammensetzung zur Behandlung von degenerativen Gelenkerkrankungen

NEUE POLYMER ZUBEREITUNGEN ENTHALTENDE PERLUORIERTE VERBINDUNGEN ZUR TECHNISCHEN HANDHABUNG VON ZELLEN UND GEWEBE BEI TRANSPLANTATIONEN, UM DEN METABOLISMUS UND DIE ÜBERLEBENSRATE DER ZELLEN ZU VERBESSERN, SOWIE VERFAHREN ZU DEREN HERSTELLUNG

Neues Chondroitinsulfat und Verfahren zu seiner Herstellung

Intramolecular transesterification of material, especially plant extract, containing cyclic polyhydroxy compounds, e.g. to prepare bioactive natural products, carried out at elevated temperature and pressure

Intramolecular transesterification of starting materials containing cyclic polyhydroxy compounds (e.g. phenylethanoids) is carried out at a pressure of 1-20 x 103> Pascals and a temperature of 40-250[deg]C, using an autoclave, sealed glass tube, distillation apparatus, extractor (e.g. Soxhlet) or perforator as apparatus. ACTIVITY : Antiinflammatory. MECHANISM OF ACTION : None given in the source material.

Glycosaminoglycanes selectively O-acylés.

RATIONALLY DESIGNED ONE, LYASEN DERIVED FROM CHONDROITINASE B

PROCEDURE FOR THE PHYSICAL DEPOLYMERISATION PRODUCTS RECEIVED FROM GLYCOSAMINOGLYCANEN AND FROM IT

OLIGOSACCHARIDE WITH ANTIATHEROSCLEROTI EFFECT.

Procedure for the production of new salts of the Chondroitinschwefelsäure

SULFATED GLYKOSAMINOGLYKURONANE WITH ANTITHROMBOTI EFFECT.

CONTAINING IN VIVO MEANS RADIOACTIVE ONE METAL IONS - CHELATEN WITH ACID SACCARIDEN AND GLYCOSAMINOGLYCANEN GIVING

INTERLACED COPOLYMERS ON THE BASIS OF NOT INTERLACED POLYCARBONSÄUREPOLYMEREN

STENCILS ON BASIS MANUFACTURED BY KOLLAGEN AND SYNTHETIC ONE POLYMER USING A MULTI-LEVEL REACTION

INJECTABLE CHONDROITIN POLYSULPHATE

"Biotechnological sulphated chondroitin sulphate at position 4 or 6 on the same polysaccharide chain, and process for the preparation thereof"

The present invention discloses a process for the production of chondroitin sulphate with an average molecular weight (Mw) of 10-30 kDa by chemical sulphation starting from an unsulphated chondroitin backbone, obtained in turn by acid hydrolysis of capsular polysaccharide K4 made directly from E. coli strain O5:K4:H4, or directly produced from a genetically modified strain of E. coli. Sulphation of the N-acetyl-D-galactosamine residue at position 4 or 6 takes place simultaneously in the same polysaccharide chain, simulating the sulphation pattern observed in natural chondroitin sulphate, unlike the sulphation obtained with the synthesis methods described to date.

GLYCOSAMINOGLYCAN DRUG COMPLEXES

Shark-like chondroitin sulphate and process for the preparation thereof

The present invention concerns a shark-like chondroitin sulphate and a process for the preparation thereof. In particular, the present invention relates to a shark¬ like chondroitin sulphate, showing a very low amount of 4-sulphate, a high charge density and a biological activity comparable to natural chondroitin sulphates; the invention also relates to a process for the preparation of said shark-like chondroitin sulphate affording substantially higher productivities and better reproducibility of product quality. The shark-like chondroitin sulphate of the invention shows a high molecular mass and charge density; its in vitro biological and anti-inflammatory effectiveness, comparable to the ones of natural products make this polysaccharide potentially useful as a drug in pharmaceutical preparations and nutraceuticals.

Compositions containing chondroitin sulphate, proteolytic enzymes and sulphydryl compounds for improving the bioavailability of chondroitin sulphate

The present invention describes combinations comprising chondroitin sulphate (CS), one or more enzymes or enzymatic mixtures possessing proteolytic activity, and sulphydryl compounds, for the treatment and prevention of osteoarthritis and correlated acute and chronic inflammatory processes, or as nutraceutical compositions for the maintenance of musculoskeletal well-being in humans and animals. The characteristic of said combinations is that they increase the intestinal absorption of CS when administered orally. The effect of said combinations is exerted on a wide range of molecular weights of CS, including CS samples with very low molecular weights which already possess greater bioavailability than samples with a higher molecular weight. The effect is exerted on CS samples of any origin.

CHONDROITIN SULPHURIC ACID SALTS

MIXED BUTYRIC-FORMIC ESTERS OF ACID POLYSACCHARIDES, AND THEIR PREPARATION AND USE AS SKIN COSMETICS

Disclosed are acid polysaccharides characterised by the concomitant presence of alcohol groups esterified with butyric and formic acids.

PROCESS FOR THE SYNTHESIS OF CONJUGATES OF GLYCOSAMINOGLYCANES (GAG) WITH BIOLOGICALLY ACTIVE MOLECULES, POLYMERIC CONJUGATES AND RELATIVE USES THEREOF

The present invention relates to a process for the synthesis of conjugates of glycosaminoglycanes (GAG) with biologically active molecules of varying nature, comprising small molecules and macro-molecules. In particular, the present invention relates to the conjugation of hyaluronic acid (HA) and its derivatives with polypeptides and proteins with a biological action, such as, for example, interferons, erythropoietins, growth factors, insulin, cytokines, antibodies and hormones. An object of the present invention also relates to isolatable intermediates obtained by the partial or total reaction of GAG with protected amino aldehydes in the conjugation process mentioned above.

PROCESS FOR THE PREPARATION OF AN INJECTABLE CHONDROITIN POLYSULFATE, A PRODUCT WHICH CAN BE OBTAINED BY THIS PROCESS AND A PHARMACEUTICAL COMPOSITION

The invention relates to a process for the preparation of an injectable chondroitin polysulfate comprising; A) oxidatively depolymerizing crude chondroitin polysulfate B) if necessary bleaching the depolymerized chondroitin polysulfate with peracetic acid, C) subjecting the thus obtained product once or twice to precipitation with methanol, ultrafiltration or both precipitation with methanol acid ultrafiltration for fractionation in respect of molecular weight, D) if necessary demineralizing the fractionated product with cation exchangers, and E) if necessary, decolorizing the thus obtained product with active charcoal. The invention further relates to a chondroitin polysulfate prepared by the above process, the process of the invention produces chondroitin polysulfate with low toxicity thereby enabling the risk free therapeutic use of these substances in the form of an injection.

COMPLEXES BETWEEN AN AMPHIPHILIC POLYMER AND AN OSTEOGENIC PROTEIN OF THE BMPS FAMILY

L'invention concerne un complexe polymère amphiphile-BMP, stable physiquement et chimiquement, soluble dans l'eau, caractérisé en ce que: les polymères amphiphiles sont constitués d'un squelette polysaccharide hydrophile fonctionnalisé par des substituants hydrophobes et des groupements hydrophiles la BMP est choisie dans le groupe des BMP (Bone morphogenetic Proteins) thérapeutiquement actives, le ratio massique polymère/BMP est inférieur ou égal à 700. L'invention concerne également le procédé de préparation du complexe polymère amphiphile-BMP en milieu aqueux et en absence de solvant organique susceptible de dénaturer la protéine. L'invention comprend également les compositions thérapeutiques de complexe polymère amphiphile-BMP selon l'invention.

POLYSACCHARIDE DERIVATIVES INCLUDING AN ALKENE UNIT AND THIOL-CLICK CHEMICAL COUPLING REACTION

La présente invention a pour objet des polysaccharides greffés avec un motif comprenant une double-liaison carbone-carbone, des polysaccharides greffés avec un motif comprenant une double-liaison carbone-carbone fonctionnalisée par un motif thioéther, les procédés de préparation de ces com posés, les compositions comprenant de tels composés et les matériaux comprenant de tels matériaux ou compositions.

BIOTECHNOLOGICAL PRODUCTION OF CHONDROITIN

Chondroitin is produced by culturing a recombinant microorganism which is obtained by inactivation of a gene encoding an enzyme responsible of fructose residues addition to the linear chondroitin polysaccharide in a microorganism producing a fructosylated derivative of chondroitin.

LOW-MOLECULAR-WEIGHT BIOTECHNOLOGICAL CHONDROITIN 6-SULPHATE FOR PREVENTION OF OSTEOARTHRITIS

Disclosed is a low-molecular-weight (1000-5000 daltons) chondroitin sulphate (CS) produced by chemical sulphation and subsequent depolymerisation of a non-sulphated chondroitin backbone obtained with biotechnology techniques. The CS described is substantially monosulphated, mainly at the 6-position, with very little sulphation at the 4-position, and with a mono/disulphated disaccharide ratio and charge density similar to those of natural CS. Said biotechnological chondroitin 6-sulphate (C6S) is useful in the treatment and prevention of osteoarthritis and in acute and chronic inflammatory processes.

USES OF NON-SULPHATED CHONDROITIN

Chondroitin, a metabolic intermediate of chondroitin sulphate biosynthesis in mammals and other living organisms, possesses biological properties different from those of chondroitin sulphate, and can be advantageously used for applications in the pharmaceutical, nutraceutical, cosmeceutical and medical device fields. Chondroitin has biostimulating, anti-inflammatory and antimicrobial activity and can be used in the treatment of osteoarthritis, eye disorders, interstitial cystitis, lung disorders, inflammatory disorders in general, oncological disorders, peritoneal dialysis, tissue biorevitalisation and wound repair, as a skin filler, and as bioresorbable scaffolds.

POLYCARBOXYLIC BASED CROSS-LINKED COPOLYMER

L'invention concerne des copolymères réticulés à base de polymères polycarboxyliques non réticulés, lesdits copolymères contenant au moins un polysaccharide polycarboxylique. L'invention concerne également un procédé de préparation de ces copolymères et leur utilisation notamment comme support dans les compositions pharmaceutiques. ...

Verfahren zur Herstellung eines blutgerinnungshemmenden Mittels.

Verfahren zur Herstellung von Chondroitin-polyschwefelsäureestern.

Verfahren zur Herstellung von abgebauten Chondroitinpolyschwefelsäureestern

Verfahren zur Herstellung von Polyschwefelsäureester von Chondroitin

Procédé de préparation d'un sel de l'acide chondroïtine sulfurique forme A ou C

PROCEDURE FOR THE PRODUCTION OF A INJECT-CASH CHONDROITINPOLYSULFATES, FROM THIS AVAILABLE PRODUCT AND ITS USE FOR THE PRODUCTION OF PHARMACEUTICAL PREPARATIONS.

Method of obtaining chondroitin sulfuric acid from organs cartilage of avian origin.

Chondroitin sulphuric acid salts with galactosamine or glucosamine

Salts (I) of chondroitin sulphuric acid with D-galactosamine or D-glucosamine are new. (I) is pref. 4- and/or 6-chondroitin- sulphate. The mol.wt. of chondroitin sulphuric acid is 10000-30000 Da. (I) is prepd. e.g. by reacting free acid with D-galactosamine or D-glucosamine and pptg. the prod.

LOW -MOLECULAR -WEIGHT BIOTECHNOLOGICAL CHONDROITIN 6 - SULPHATE FOR PREVENTION OF OSTEOARTHRITIS

PHARMACEUTICAL COMPOSITIONS, CONTAINING CHONDROITIN SULFATE AND DERIVATIVES OF HYALURONIC ACID

COMPOSITIONS CONTAINING CHONDROITIN SULPHATE, PROTEOLYTIC ENZYMES AND SULPHYDRYL COMPOUNDS FOR IMPROVING THE BIOAVAILABILITY OF CHONDROITIN SULPHATE

BIOTECHNOLOGICAL SULPHATED CHONDROITIN SULPHATE AT POSITION 4 OR 6 ON THE SAME POLYSACCHARIDE CHAIN, AND PROCESS FOR THE PREPARATION THEREOF

ANALOG SHARK HONDROYITYNSULFATU AND HOW TO OBTAIN

COMPOSITIONS CONTAINING CHONDROITIN SULPHATE, PROTEOLYTIC ENZYMES AND SULPHYDRYL COMPOUNDS FOR IMPROVING THE BIOAVAILABILITY OF CHONDROITIN SULPHATE

LOW-MOLECULAR-WEIGHT BIOTECHNOLOGICAL CHONDROITIN 6-SULPHATE FOR PREVENTION OF OSTEOARTHRITIS

PHARMACEUTICAL COMPOSITIONS, CONTAINING CHONDROITIN SULFATE AND DERIVATIVES OF HYALURONIC ACID

CHONDROITIN SULFATE SHARK TYPE AND METHOD OF ITS PRODUCTION

BIOTECHNOLOGICAL SULPHATED CHONDROITIN SULPHATE AT POSITION 4 OR 6 ON THE SAME POLYSACCHARIDE CHAIN, AND PROCESS FOR THE PREPARATION THEREOF

Novel chondroitin sulfate having decreased molecular weight and use thereof

It is intended to provide a chondroitin sulfate having a decreased molecular weight which is useful as an inhibitor of peritoneal disorder caused by long-term use of a peritoneal dialysis fluid containing glucose or a polysaccharide of glucose as an osmotic substance or is useful as an osmotic substance in a peritoneal dialysis fluid. The chondroitin sulfate having a decreased molecular weight of the invention as a resolution means is characterized in that it has a weight average molecular weight of from 1000 to 20000 and comprises a constituent disaccharide unit represented by the following structural formula in an amount of from 65% to 100% (molar ratio) of the total. -[4GlcAbeta1-3GalNAc(6S)beta1]-] In the formula, GlcA represents a D-glucuronic acid residue; GalNAc represents a N-acetyl-D-galactosamine residue; beta1-3 represents a beta1-3 glycosidic linkage; beta1-4 represents a beta1-4 glycosidic linkage; and (6S) indicates that a group at the 6th position in the monosaccharide residue ...

PROCEDE DE PREPARATION DE SULFATE DE CHONDROITINE ET COMPOSITION PHARMACEUTIQUE CONTENANT CE DERNIER

L'INVENTION CONCERNE UN PROCEDE DE PREPARATION DU SULFATE DE CHONDROITINE ACTIF A OU DU SULFATE DE CHONDROITINE ACTIF C OU D'UN DE LEURS MELANGES, EN FORMANT UNE SOLUTION AQUEUSE DES SULFATES DE CHOINDROITINE A PARTIR D'UN MATERIAU DE DEPART APPROPRIE, TEL QU'UN TISSU DE MAMMIFERE, EN AJOUTANT A LA SOLUTION UN AGENT COMPLEXANT FORMANT UN COMPLEXE INSOLUBLE DANS L'EAU AVEC LES SULFATES DE CHONDROITINE ET A RECUEILLIR CES SULFATES PAR SCISSION DU COMPLEXE. LES SULFATES DE CHONDROITINE ACTIFS SONT UTILISES COMME MEDICAMENT ANTI-COAGULANT POUR LE TRAITEMENT DES MALADIES CIRCULATOIRES ET CARDIAQUES.

GLYCOSAMINOGLYCANES SELECTIVELY O-ACYLES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS THE CONTAINER

PROCESS FOR PREPARING SODIUM CHONDROITIN SULFATE

Production of chondroitin sulfate useful for treating arthritis and ocular disorders comprises hydrolyzing bovine or porcine cartilage with Bacillus licheniformis alkaline protease

La présente invention se rapporte au domaine de la chimie et plus particulièrement à celui de la chimie thérapeutique. Elle se rapporte à un procédé de production et de purification d'acide chondroïtine sulfurique à partir de tissus d'origine animale et principalement d'origine porcine ou bovine, qui consiste à soumettre des tissus cartilagineux à un broyage puis à une hydrolyse enzymatique par une hydrolase spécifique puis à une filtration et ensuite à une ou plusieurs dialyses contre de l'eau, séparation des acides aminés et des petits peptides et enfin précipitation par un alkanol pour obtenir de l'acide chondroïtine sulfurique purifié sous forme de sel de sodium. Utilisation comme principe actif de médicament.

Method for extraction of heparin derived from by-product of pork

콘드로이틴 술페이트, 단백질 분해성 효소 및 술피드릴 화합물을 포함하는 콘드로이틴 술페이트의 생체 이용율을 개선하기 위한 조성물

... 본 발명은 콘드로이틴 술페이트(CS), 하나 이상의 효소 또는 단백질 분해성 활성을 갖는 효소적 혼합물, 및 술피드릴 화합물을 포함하는 관절염 및 관련된 급성 및 만성 염증성 과정의 치료 및 예방을 위한, 또는 건강 기능성 조성물로서 인간 및 동물의 근골격의 건강을 유지하기 위한 조합을 설명한다. 상기 조합의 특성은 이들이 경구 투여시의 CS의 장내 흡수를 증가시키는 것이다. 상기 조합의 효과는, 높은 분자량을 가진 샘플보다 더 큰 생체 이용율을 이미 갖는 것으로 알려진 매우 낮은 분자량을 갖는 CS 샘플을 포함하여, 넓은 범위의 분자량의 CS에 대하여 발휘된다. 상기 효과는 임의의 기원의 CS 샘플에 대하여 발휘된다.

GLYCOSAMINOGLYCANS WITH VERY LOW METHANOL CONTENT

The present invention relates to a process for preparing a glycosaminoglycan with a methanol content less than or equal to 10 ppm, in which water is sprayed under stirring on the glycosaminoglycan and it is irradiated with microwaves under vacuum at a temperature less than 70º C. The process allows formulating said glycosaminoglycan, preferably chondroitin sulfate or hyaluronic acid in a product suitable for use in a food supplement or in a functional food.

PREPARATION PROCESS OF OLIGOGLYCOSAMINOGLYCAN, AND REDUCING END GLUCURONIC ACID TYPE OLIGOCHONDROITIN SULFATE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

A sugar donor having a glucuronic acid or iduronic acid derivative at the reducing end and in which a leaving group is added to the reducing end hydroxyl group to be glycosylated and the other hydroxyl groups and the carboxyl groups are protected, is subjected to glycosylation reaction with a sugar acceptor having a N-acylgalactosamine derivative at the reducing end and in which the non-reducing end hydroxyl group to be glycosylated is free and the other hydroxyl groups are protected, in the presence of (A-3) a particular promoter. Provided is a process for preparing an oligoglycosaminoglycon of an intended chain length composed of four or more constituent sugars in highly stereoselectively, high yield and high purity.

Cross-Linked Polymer Based Hydrogel Material Compositions, Methods and Applications

A hydrogel material composition includes: (1) an alginate (or other cross-linking polymer) material; (2) an optional -hydroxy carboxylate material; and (3) an iron cation material. The hydrogel material composition with or without the -hydroxy-carboxylate material may be used in a photolithographic imaging application or a photorelease application within the context of a photoirradiation induced reduction/oxidation reaction of an iron (III) cation material to form an iron (II) cation material.

Process for the physical depolymerization of glycosaminoglycanes and products obtained therefrom

The invention relates to a process for the depolymerization of glycosaminoglycanes characterized by the use of UVC radiation. The invention also relates to the intermediate depolymerized heparin obtained by the process. The intermediate depolymerized heparin can be dissolved in a buffer solution and fractionated by Gel Permeation for obtaining the desired Molecular Weight.

Photo-crosslinked hydrogel material and preparation, composition, and application thereof photo-crosslinked hydrogel

This invention provides preparations, compositions, products, and applications of photo-crosslinked hydrogels. Component A—a photosensitive polymer derivative, component B—the photoinitiator, and auxiliary component C—other biocompatible polymer derivative each are respectively dissolved in a biocompatible medium to obtain solution A, solution B, and solution C. The solution A, the solution B, and the optional solution C are mixed homogenously to obtain a hydrogel precursor solution. The hydrogel precursor solution is subject to irradiation of the UV light for photocoupled crosslinking to form a photo-crosslinked hydrogel. The photo-crosslinked hydrogel exhibit rapid speed of photo-curing, strong tissue adhesion, excellent mechanical properties, good biocompatibility, and excellent clinical operability. In addition, this invention also provides a kit for making the photo-crosslinked hydrogel, and applications thereof in tissue engineering, regenerative medicine, 3D printing, and as a carrier ...

Complex obtained from hyaluronic acid or a salt thereof and chondroitin sulphate mixtures

PREPARATION PROCESS OF OLIGOGLYCOSAMINOGLYCAN, AND REDUCING END GLUCURONIC ACID TYPE OLIGOCHONDROITIN SULFATE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

Iron complexes with sulfomucopolysaccharides salts

Complexes of iron with sulfomucopolysaccharides salts containing FeII or FeIII in amount from 6 to 11% w/w useful in the martial therapy.

SALMON-ORIGIN CHONDROITIN SULFATE

A novel chondroitin sulfate which can be produced more economically in a large amount and is expected as being useful for various purposes and processes for producing the same. Namely, a novel chondroitin sulfate which has an intermediate structure between the conventionally known whale-origin chondroitin sulfate and shark-origin chondroitin sulfate and is expected as useful for various purposes in the fields of drugs, cosmetics, food additives, etc. Aprocess for producing the above-described chondroitin sulfate comprises grinding salmon nasal cartilage at a low temperature, defatting the ground matter, then treating it with an alkali and pronase, centrifuging the thus obtained liquid digested matter and then precipitating it from ethanol; and another process wherein the precipitate thus obtained is further treated with a cation exchange resin.

СШИТЫЕ СОПОЛИМЕРЫ НА ОСНОВЕ ПОЛИКАРБОКСИЛЬНЫХ ПОЛИМЕРОВ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, СОДЕРЖАЩИЕ СШИТЫЕ СОПОЛИМЕРЫ

Описаны сшитые сополимеры на основе несшитых поликарбоксильных полимеров и сшивающего агента, содержащего, по меньшей мере, две аминофункции, причем названные несшитые сополимеры содержат, по меньшей мере, один поликарбоксильный полисахарид и, по меньшей мере, другой несшитый поликарбоксильный полимер, не являющийся поликарбоксильным полисахаридом, причем поликарбоксильный полимер выбран из группы, включающей поликарбоновые поликислоты или их частично или полностью замещенные производные, например их сложные эфиры, амиды или соли, сополимеры, содержащие звенья указанных поликарбоновых кислот или их названных производных, или смеси этих поликарбоксильных полимеров, и/или их названных производных, и/или их сополимеров, а также фармацевтические композиции для контролируемого выделения активного начала, в частности в толстой кишке. 4 с. и 16 з.п. ф-лы, 1 табл., 2 ил.

СЛОЖНЫЕ ЭФИРЫ ГЛИКОЗАМИНОГЛИКАНА, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ИХ ПРИМЕНЕНИЕ В КОМПОЗИЦИЯХ ОФТАЛЬМИЧЕСКОГО НАЗНАЧЕНИЯ

Изобретение может быть использовано в офтальмологии и относится к сложному эфиру гиалуроновой кислоты, в которой по меньшей мере часть гидроксильных групп, присутствующих на остатке N-ацетилглюкозамина, этерифицирована кроцетином или биксином, композиции на его основе, способу получения указанного эфира и его применения для защиты глаз от синего света. Предложенный способ включает получение тетрабутиламмонийной соли гиалуроновой кислоты путем солеобразования ионообменной смолы с водным раствором гидроксида тетрабутиламмония с последующим промыванием смолы водой и пропусканием через нее водного раствора гиалуроната натрия, сбором и вымораживанием элюата, полученную таким образом соль затем подвергают взаимодействию с соответствующим апокаротиноидом при нагревании, карбоксильная функциональность которого активирована реакцией при комнатной температуре с карбонилдиимидазолом в диметилформамиде, причем смесь оставляют при перемешивании, затем продукт осаждают добавлением хлорида натрия и этанола ...

OLIGOSACCHARIDE MIT ANTIATHEROSCLEROTISCHER WIRKUNG.

Salze von Glykosaminoglykanen mit Aminosäureester, ihre Herstellung sowie sie enthaltende pharmazeutische Zusammensetzungen

POLYSACCHARIDE DERIVATIVES OF ANAESTHETIC COMPOUNDS

KOLLAGEN POLYMER KONJUGATE ONE

OLIGOSACCHARIDE WITH BIOLOGICAL ACTIVITY AND PROCEDURE FOR THE PRODUCTION FROM GLYKOSAMINOGLYKANEN

PROCEDURE FOR THE PRODUCTION OF A INJECT-CASH CHONDROITINPOLYSULFATES

PROCEDURE FOR THE PRODUCTION OF CHONDROITINSULFATEN FROM K4-POLYSACCHARID AND SO MANUFACTURED PRODUCTS

DERMATANSULFATOLIGOSACCHARIDE, PROCEDURE FOR YOUR PRODUCTION AND THESE CONTAINING PHAMAZEUTI COMPOSITIONS

OLIGOSACCHARIDEMISCHUNGEN WITH ANTITHROMBOTI EFFECT

Method of covalent coupling

Biocompatible polymer conjugates

Collagen-synthetic polymer matrices prepared using multiple step reaction

Complexes between an amphiphilic polymer and an osteogenic protein of the BMPs family

Low-modification biocompatible high polymer sulfhydryl-modified derivatives, cross-linked material thereof, and uses of said material

Disclosed are low-modification biocompatible high polymer sulfhydryl-modified derivatives. The derivatives have a very low degree of sulfhydryl modification, and maintain to the greatest extent possible the initial structure, physiological function, and biocompatibility of the biocompatible high polymer. At the same time, the sulfhydryl introduced effectively carries out chemical cross-linking so as to produce a biocompatible high polymer cross-linked material having a low degree of cross-linking. Also disclosed is a type of disulfide cross-linked biocompatible high polymer cross-linked material. This cross-linked material has a low degree of cross-linking and not only maintains to the greatest extent possible the initial structure, physiological functions, and biocompatibility of the biocompatible high polymer, but also delays metabolization of the biocompatible high polymer in the body and reduces solubility. This satisfies a variety of needs in terms of clinical application. The present ...

Preparation and/or formulation of proteins cross-linked with polysaccharides

Therapeutic compositions and/or formulations are provided, comprising: at least one cross- linked protein matrix, wherein the at least one cross-linked protein matrix comprises at least one protein residue and at least one saccharide-containing residue, and methods of producing the same. The cross-linked protein matrix may be derived from cross-linking a full length or substantially full length protein, such as tropoelastin, elastin, albumin, collagen, collagen monomers, immunoglobulins, insulin, and/or derivatives or combinations thereof, with a saccharide containing cross-linking agent, such as a polysaccharide cross-linking agent derived from, for example, hyaluronic acid or a cellulose derivative. The therapeutic compositions may be administered topically or by injection. The present disclosure also provides methods, systems, and/or kits for the preparation and/or formulation of the compositions disclosed herein.

Preparation and/or formulation of proteins cross-linked with polysaccharides

Therapeutic compositions and/or formulations are provided, comprising: at least one cross linked protein matrix, wherein the, at least one cross-linked protein matrix comprises at least one protein residue and at least one saccharide-containing residue, and methods of producing the 5 same. The cross-linked protein matrix may be derived from cross-linking a full length or substantially full length protein, such as tropoelastin, elastin, albumin, collagen, collagen monomers, immunoglobulins, insulin, and/or derivatives or combinations thereof, with a saccharide containing cross-linking agent, such as a polysaccharide cross-linking agent derived from, for example, hyaluronic acid or a cellulose derivative. The therapeutic compositions may 0 be administered topically or by injection. The present disclosure also provides methods, systems, and/or kits for the preparation and/or formulation of the compositions disclosed herein.

RATIONALLY DESIGNED POLYSACCHARIDE LYASES DERIVED FROM CHONDROITINASE B

The invention relates to rationally designed polysaccharide lyases and uses thereof. In particular, the invention relates to modified chondroitinase B. The modified chondroitinase B enzymes of the invention are useful for a variety of purposes, including cleaving and sequencing polysaccharides such as glycosaminoglycans (GAGs) as well as removing polysaccharides from a solution. The invention also includes methods of inhibiting anticoagulant activity, inhibiting angiogenesis, treating cancer, and inhibiting maternal malarial infection.

PROCESS FOR THE PREPARATION OF AN INJECTABLE CHONDROITIN POLYSULFATE, A PRODUCT WHICH CAN BE OBTAINED BY THIS PROCESS AND A PHARMACEUTICAL COMPOSITION

GLYCOSAMINOGLYCAN SALTS, PROCESSES FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION CONTAINING THEM

Salts of glycosaminoglycans (heparin, its fractions or fragments "supersulfatated", dermatan sulfate, heparan sulfate, modified heparins) with cations of formula I (I) wherein R1, R2, R3 and R4 represent for instance H, alkyl, cycloalkyl; R5 and R6 represent H, alkyl or aryl; R7 and R8 represent H or alkyl; n and m range from 1 to 4 whereas X = -O-CO-O-; -O-CO-; -NH-CO-; -NH-CO-NH- etc., show the typical pharmacological properties of the glycosaminoclycans themselves also by oral or rectal administration.

CHONDROITIN DRUG COMPLEXES

POLYSACCHARIDE BIOMATERIALS AND METHODS OF USE THEREOF

The invention includes a medical hydrogel made from polymerized polysaccharide macromers. The macromers are preferably polysaccharides decorated with polymerizable groups, for example, methacrylates. The macromers may also be made into polymers of at least two macromers polymerized together. These polymers are preferably multi-armed or high-molecular weight and used for medical uses, for example, making coatings on medical devices. Macromers of N- vinylpyrrolidone are also disclosed herein.

CHONDROITIN SULFATE DERIVATIVE AND AGENT FOR TREATING BLADDER DISEASES

Provided is a compound in which a group derived from chondroitin sulfuric acid and a group derived from a steroid are covalently bonded together via a spacer represented by general formula (I). In the formula, m represents an integer of 0 or 1. Here, if m = 0, R1 represents a group selected from the group consisting of electron-donating groups and steric hindrance groups. If m = 1, R1 represents a group selected from the group consisting of a hydrogen atom, electron-donating groups and steric hindrance groups. -HN-(CH2)m-CHR1-CO- (I) ...

METHOD OF PRODUCING SACCHARIDE HAVING SULFATE GROUP AND/OR PHOSPHATE GROUP

... [Problem] The purpose of the present invention is to provide a method for uniformly and efficiently producing a sugar having a sulfate group and/or phosphate group in the molecule or a compound containing the sugar. [Solution] The present invention provides a method for producing a sugar having a sulfate group and/or phosphate group. This method includes (a) a step for preparing a "first sugar having an unprotected sulfate group and/or unprotected phosphate group" and a "second sugar having an unprotected sulfate group and/or unprotected phosphate group," and (b) a step for condensing the first sugar and second sugar prepared in step (a) with each other.

TARGETED GLYCOSAMINOGLYCAN POLYMERS BY POLYMER GRAFTING AND METHODS OF MAKING AND USING SAME

The present invention relates to methodology for polymer grafting by a polysaccharide synthase and, more partic-ularly, polymer grafting using the hyaluronate or chondroitin or heparin/heparosan synthases from Pasteurella, in order to create a variety of glycosaminoglycan oligosaccharides having a natural or chimeric or hybrid sugar structure with a targeted size that are substantially monodisperse in size. The present invention also relates to methodology for polymer grafting by a polysachharide synthase to form glycosaminoglycan polymers having an unnatural structure.

NEW BIOMATERIAL FROM WHARTON'S JELLY OF THE HUMAN UMBILICAL CORD

The present invention relates to a biomaterial, specifically a hydrogel, formed from the extracellular matrix of the umbilical cord for its application in regenerative medicine. The invention particularly relates to a biomaterial made up of glycosaminoglycans isolated exclusively from the Wharton's jelly of the umbilical cord which can optionally contain cells, and also to the methods for the production and use thereof.

MERCAPTO-MODIFIED BIOCOMPATIBLE MACROMOLECULE DERIVATIVES WITH LOW DEGREE OF MERCAPTO-MODIFICATION AND THE CROSS-LINKED MATERIALS AND USES THEREOF

The present invention discloses a mercapto-modified biocompatible macromolecule derivative with a low degree of modification. The mercapto-modified biocompatible macromolecule derivative not only maintains the initial structure, physiological function and biocompatibility as much as possible, but also allows the preparation of the biocompatible macromolecule cross-linked material with a low degree of cross-linking through the effectively chemical cross-linking with the introduced mercapto group. The present invention further discloses a disulfide-bond cross-linked biocompatible macromolecule material with a very low degree of cross-linking. The disulfide-bond cross-linked biocompatible macromolecule material not only maintains the initial structure, physiological function and biocompatibility of the biocompatible macromolecule as much as possible, but also effectively prolongs turn over and reduces the solubility of the biocompatible macromolecule in vivo, better meeting the requirements ...

METHOD FOR PRODUCTION OF SUGAR OXAZOLINE DERIVATIVE

Disclosed is a method for producing an oxazoline derivative from a non-pr otected sugar in a simple manner. Also disclosed is a method for producing a glycoside by utilizing the product of the aforementioned method. A sugar ox azoline derivative is synthesized in one step in an aqueous solution from a sugar having a free hemiacetal hydroxy group and an amide group by using a h aloformamidinium derivative as a dehydration/condensation agent. A glycoside is produced by using the oxazolidine derivative as a sugar donor and also u sing a sugar dehydrogenase. The method can be applied to the production of a compound having a long sugar chain, and is therefore useful for the product ion of a physiologically active oligosaccharide, a carrier for a drug delive ry system, a surfactant, a carbohydrate pharmaceutical, a glycopeptide, a gl ycoprotein, a carbohydrate polymer or the like.

LOW-MOLECULAR-WEIGHT BIOTECHNOLOGICAL CHONDROITIN 6-SULPHATE FOR PREVENTION OF OSTEOARTHRITIS

Disclosed is a low-molecular-weight (1000-5000 daltons) chondroitin sulphate (CS) produced by chemical sulphation and subsequent depolymerisation of a non-sulphated chondroitin backbone obtained with biotechnology techniques. The CS described is substantially monosulphated, mainly at the 6-position, with very little sulphation at the 4-position, and with a mono/disulphated disaccharide ratio and charge density similar to those of natural CS. Said biotechnological chondroitin 6-sulphate (C6S) is useful in the treatment and prevention of osteoarthritis and in acute and chronic inflammatory processes.

Biotechnological Production of Chondroitin

Chondroitin is produced by culturing a recombinant microorganism which is obtained by inactivation of a gene encoding an enzyme responsible for addition of fructose residues to the linear chondroitin polysaccharide in a microorganism producing a fructosylated derivative of chondroitin.

Porous composite biomaterials and production method of the same

The invention discloses a porous composite biomaterial comprising of poly(γ-glutamic acid)-g-chondroitin sulfate (γ-PGA-g-CS) copolymer and poly(ε-caprolactone). The composite biomaterial provides a three-dimensional microenviroment for using as a scaffold for tissue engineering and for supporting the attachment and proliferation of cells. The invention also discloses a method of producing a porous composite biomaterial.

Metal-polysaccharide conjugates: compositions, synthesis and methods for cancer therapy

The current disclosure, in one embodiment, includes a polysaccharide conjugate. This conjugate has a polysaccharide and at least one liner covalently bound to the polysaccharide. The conjugate also has at least one metal conjugated by said linker. According to another embodiment, the disclosure provides a method of synthesizing a polysaccharide conjugate by covalently bonding a linker to a polysaccharide to obtain an intermediate and by conjugating said intermediate to a metal to form a polysaccharide conjugate. This conjugate has a higher relaxivity, so it is suitable to be used as a contrast medium for hybrid camera.

METHOD FOR THE PREPARATION OF SODIUM CHONDROITIN SULPHATE

The present invention concerns a method for obtaining sodium chondroitin sulphate from cartilage, notably of avian origin, as well as a sodium chondroitin sulphate preparation. 1. Sodium chondroitin sulphate preparation comprising over 90% of sodium chondroitin sulphate which has a polydispersity index less than or equal to 1.47 , measured by steric exclusion chromatography SEC-MALLS.2. Sodium chondroitin sulphate preparation according to claim 1 , having a mean molecular mass by weight (Mw) greater than or equal to 20 claim 1 ,000 Daltons claim 1 , measured by steric exclusion chromatography SEC-MALLS.3. Sodium chondroitin sulphate preparation according to or claim 1 , having a mean molecular mass by number (Mn) greater than or equal to 14 claim 1 ,000 Daltons claim 1 , measured by steric exclusion chromatography SEC-MALLS.4. Sodium chondroitin sulphate preparation according to claim 1 , having a density between 0.8 and 1.5. Sodium chondroitin sulphate preparation according to claim 1 , comprising less than 0.09% proteins measured according to the Bradford method.6. Sodium chondroitin sulphate preparation according to claim 1 , comprising less than 2.0% proteins measured according to the Lowry method.7. Sodium chondroitin sulphate preparation according to claim 1 , containing quantities that are not detectable by steric exclusion chromatography SEC-MALLS of sodium chondroitin sulphate aggregates and high molecular mass compounds of a size greater than 10g/mol.8. Sodium chondroitin sulphate preparation according to claim 1 , presenting a peak maximum molecular mass (Mp) greater than or equal to 22 claim 1 ,000 Daltons claim 1 , measured by steric exclusion chromatography SEC-MALLS.9. A method for the preparation of sodium chondroitin sulphate from cartilage comprising the following steps:a. Hydrolysis of the cartilage in aqueous medium,b. Thermal treatment of the hydrolysis between 90 and 100° C. for 2 to 10 hours,c. Separation of the sodium chondroitin sulphate ...

NOVEL CHONDROITIN SULFATE HAVING DECREASED MOLECULAR WEIGHT AND USE THEREOF

A chondroitin sulfate having a decreased molecular weight which has utilization as an inhibitor of peritoneal disorder caused by long-term use of a peritoneal dialysis fluid containing glucose or a polysaccharide thereof as an osmotic agent, utilization as an osmotic agent in a peritoneal dialysis fluid, and the like. The chondroitin sulfate having a decreased molecular weight of the present invention as a means for achieving the object is characterized by having a weight average molecular weight of from 1000 to 20000 and containing a constituent disaccharide unit represented by the following structural formula in an amount of from 65% to 100% (molar ratio) of the total: 17-. (canceled)9. The method of claim 8 , wherein the dialysis fluid comprises glucose and/or a polysaccharide of glucose as an osmotic agent.10. The method of claim 8 , wherein said chondroitin sulfate is at a concentration of from 0.01% (w/v) to 1% (w/v) in the dialysis fluid.11. The method of claim 8 , wherein the dialysis fluid does not comprise glucose and/or a polysaccharide of glucose claim 8 , and said chondroitin sulfate is at a concentration of from 1% (w/v) to 10% (w/v) in the dialysis fluid.13. The method of claim 12 , wherein the administering step comprises administering the composition orally.14. The method of claim 12 , wherein the administering step comprises administering the composition parenterally.16. The method of claim 15 , wherein the administering step comprises administering the composition orally.17. The method of claim 15 , wherein the administering step comprises administering the composition parenterally. The present invention relates to a novel chondroitin sulfate having a decreased molecular weight and use thereof. More particularly, the present invention relates to a chondroitin sulfate having a decreased molecular weight which has utilization as an inhibitor of peritoneal disorder caused by long-term use of a peritoneal dialysis fluid containing glucose or a ...

USE OF LIPID CONJUGATES IN THE TREATMENT OF DISEASES

This invention provides compounds represented by the structure of the general formula (A): 2. The compound of claim 1 , wherein said lipid comprises a linear claim 1 , saturated claim 1 , mono-unsaturated claim 1 , or poly-unsaturated claim 1 , alkyl chain ranging in length from 2 to 30 carbon atoms.3. The compound of claim 2 , wherein said alkyl chain comprises a palmitic acid moiety or a myristic acid moiety.4. The compound of claim 3 , wherein said L-Z forms phosphotidylethanolamine claim 3 , phosphotidylserine claim 3 , phosphotidylinositol claim 3 , phosphotidylcholine or phosphotidylglycerol.5. The compound of claim 1 , wherein L is a phospholipid.6. The compound of claim 1 , wherein L is a sphingolipid.7. The compound of claim 1 , wherein L is a ceramide lipid.8. The compound of claim 1 , wherein L is a glycerolipid.9. The compound of claim 8 , wherein L is a deoxyglycerolipid.10. The compound of claim 1 , wherein Y is nothing.11. The compound of claim 1 , wherein any bond between L claim 1 , Z claim 1 , Y and X is either an amide or an esteric bond.12. The compound of claim 1 , wherein X is selected from the group of molecules consisting of polygeline claim 1 , hydroxyethylstarch claim 1 , dextran claim 1 , aspirin claim 1 , albumin claim 1 , alginate claim 1 , polyaminoacid claim 1 , polyethylene glycol claim 1 , lactobionic acid claim 1 , acetylsalicylate claim 1 , cholesteryl-hemmisuccinate claim 1 , maltose claim 1 , cholic acid claim 1 , polycarboxylated polyethylene glycol claim 1 , carboxymethylcellulose claim 1 , and glutaryl.13. The compound of claim 1 , wherein X is a glycosaminoglycan.14. The compound of claim 13 , wherein X is hyaluronic acid.15. The compound of claim 13 , wherein X is heparin.16. The compound of claim 13 , wherein X is chondroitin.17. The compound of claim 16 , wherein X is chondroitin sulfate18. The compound of claim 1 , wherein n is a number greater than 1. This application is a divisional application of U.S. application Ser. ...

EGGSHELL MEMBRANE SOLUBILIZATION METHOD USING ENZYMES

The present invention addresses the problem of providing an eggshell membrane solubilization method that is capable of solving the problems associated with carrying out treatment using acids and alkalis, or problems associated with the processing methods of the conventional art that use proteases; in other words, an eggshell membrane solubilization method that is capable of solving at least one of the following problems: (1) the need for pretreatment such as pulverization, sonication or boiling; (2) the need for prolonged treatment; and (3) a low decomposition rate (approximately 20%). Eggshell membranes are efficiently solubilized by using a protease in combination with a reducing agent. 1. An eggshell membrane solubilization method using the combination of a protease and a reducing agent.2. The eggshell membrane solubilization method of claim 1 , which comprises the step of subjecting eggshell membranes to the action of a protease in the presence of a reducing agent.3. The eggshell membrane solubilization method of claim 1 , which comprises the following steps (1) and (2):(1) a step of providing eggshell membranes in a solvent; and(2) a step of adding a reducing agent and a protease to the solvent, and causing reactions by them.4. The eggshell membrane solubilization method of claim 3 , wherein the pH of the reaction solution in the step (2) is from 4.5 to 9.5.5. The eggshell membrane solubilization method of claim 3 , wherein the concentration of the reducing agent is from 5 mM to 1 M.6. The eggshell membrane solubilization method of claim 3 , wherein the reaction in the step (2) is continued until no solid is found.7. The eggshell membrane solubilization method of claim 3 , which further comprises the following step (3):(3) a step of filtering the solution after the step (2), thereby removing solids.8. The eggshell membrane solubilization method of claim 1 , wherein the protease is an alkaline or neutral protease.9. The eggshell membrane solubilization method of ...

Process for obtaining chondroitin sulphated at the 4- or 6- positions of n-acetyl-galactosamine residues

Disclosed is a process for the production of chondroitin sulphate, wherein N-acetyl-galactosamine residues sulphated at the 4- or 6-positions are present on the same polysaccharide chain.

Biotechnological Production of Chondroitin

Chondroitin is produced by culturing a recombinant microorganism which is obtained by inactivation of a gene encoding an enzyme responsible for addition of fructose residues to the linear chondroitin polysaccharide in a microorganism producing a fructosylated derivative of chondroitin.

DIAMINE CROSSLINKING AGENTS, CROSSLINKED ACIDIC POLYSACCHARIDES AND MEDICAL MATERIALS

The invention provides a diamine crosslinking agent for acidic polysaccharides consisting of a diamine compound having a primary amino group at both terminals and an ester or thioester bond in the molecule, wherein the number of atom in the linear chain between at least one of the amino groups and the carbonyl carbon in the ester or thioester is 1 to 5; in particular, a diamine crosslinking agent for acidic polysaccharides which is represented by the general formula (I) below: 1. A diamine crosslinking agent for acidic polysaccharides consisting of diamine compounds having a primary amino group at both terminals and an ester or thioester bond in the molecule , wherein the number of atom in the linear chain between at least one of the amino groups and the carbonyl carbon in the ester or thioester is 1 to 5.3. The diamine crosslinking agent according to claim 2 , wherein Z is an oxygen atom.4. The diamine crosslinking agent according to claim 3 , wherein the number of atoms in the linear chain between the amino groups at both terminals is 5 to 8.5. The diamine crosslinking agent according to claim 3 , wherein the number of atoms in the linear chain between the amino groups at both terminals is 5 or 6.6. The diamine crosslinking agent according to claim 2 , wherein:{'sup': '1', 'Ris a hydrogen atom, or a substituted or unsubstituted alkyl group;'}{'sup': 2', '3', '4', '5, 'Ris a hydrogen atom, a —CONRRgroup or a —COORgroup;'}X is a single bond or an alkylene group which may be substituted by halogen;Y is a substituted or unsubstituted alkylene group;{'sup': 1', '5, 'the substituent(s) in Ris selected from the group consisting of methyl groups, phenyl groups, indolyl groups, —COORgroups and —S—Me groups; and'}{'sup': '5', 'the substituent(s) in Y is selected from the group consisting of methyl groups, phenyl groups and —COORgroups.'}7. The diamine cros slinking agent according to claim 2 , wherein:{'sup': 7', '8, 'X is a single bond; Y is a >CRRgroup; and'}{'sup': 7', ' ...

GRAFT COPOLYMER

A graft copolymer comprising: a core polymer comprising a crosslinked or non-crosslinked polysaccharide, a plurality of primary graft polymers covalently grafted to the core polymer, a plurality of secondary graft polymers covalently grafted to each primary graft polymer, an injectable dermal aesthetic formulation comprising such a graft copolymer and a method of preparing such a graft copolymer. 1. A graft copolymer comprising:a core polymer comprising a crosslinked or non-crosslinked polysaccharide,a plurality of primary graft polymers covalently grafted to the core polymer,a plurality of secondary graft polymers covalently grafted to each primary graft polymer.2. A graft copolymer according to claim 1 , wherein the core polymer comprises hyaluronic acid.3. A graft copolymer according to claim 1 , wherein the core polymer has a molecular weight in the range of 50-5000 kDa claim 1 , preferably in the range of 100-1000 kDa.4. A graft copolymer according to claim 1 , wherein the core polymer is crosslinked.5. A graft copolymer according to claim 1 , wherein the core polymer comprises a polysaccharide gel.6. A graft copolymer according to claim 1 , wherein the primary graft polymers comprise a water soluble polymer.7. A graft copolymer according to claim 1 , wherein the primary graft polymers are dextran.8. A graft copolymer according to claim 1 , wherein the primary graft polymers have a molecular weight in the range of 1-1000 kDa.9. A graft copolymer according to claim 1 , wherein the secondary graft polymers are chondroitin sulphate.10. A graft copolymer according to claim 1 , wherein the secondary graft polymers have a molecular weight in the range of 10-1000 kDa claim 1 , preferably in the range of 20-500 kDa.11. A graft copolymer according to claim 1 , wherein the primary graft polymers are covalently grafted claim 1 , directly or through a linking group claim 1 , to the core polymer by single end-point attachment.12. A graft copolymer according to claim 1 , ...

METHOD FOR CLEAVING AMIDE BONDS

A method for cleaving amide bonds, including: a) providing a molecule including an amide group; b) reacting the molecule including the amide group with a hydroxylamine salt to cleave the amide bond of the amide group. The method may further include c) recovering a product formed by the reaction of step b). 131.-. (canceled)32. A method for cleaving amide bonds , comprising:a) providing a molecule comprising an amide group, wherein the amide group is a primary, secondary or tertiary amide group;b) reacting the molecule comprising an amide group with a hydroxylamine salt to cleave the amide bond of the amide group.33. The method according to claim 32 , wherein the method further comprises:c) recovering a product formed by the reaction of step b).34. The method according to claim 32 , wherein the amide group is an N-acyl amide group claim 32 , preferably an N-acetyl amide group.35. The method according to claim 32 , wherein the molecule comprising an amide group further comprises a pH sensitive chiral center.36. The method according to claim 32 , wherein the molecule comprising an amide group further comprises a pH sensitive protecting group.37. The method according to claim 32 , wherein step b) comprises reacting the molecule comprising an amide group with the hydroxylamine salt at a temperature of 100° C. or less.38. The method according to claim 32 , wherein step b) comprises reacting the molecule comprising an amide group with the hydroxylamine salt for 2-200 hours.39. The method according to claim 32 , wherein the hydroxylamine salt is a salt formed by hydroxylamine and an acid selected from the group consisting of mineral acids and organic acids or mixtures thereof.40. The method according to claim 32 , wherein the hydroxylamine salt is a salt formed by hydroxylamine and an acid selected from the group consisting of hydrochloric acid claim 32 , hydroiodic acid claim 32 , hydrobromic acid claim 32 , acetic acid claim 32 , propionic acid claim 32 , pivalic acid ...

PRIMARY AMINE COMPOUND OR SECONDARY AMINE COMPOUND-ACIDIC POLYSACCHARIDE CONJUGATE AND PRODUCTION METHOD THEREFOR

Provided is a novel conjugate of a primary or secondary amine compound with an acidic polysaccharide, which is a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, where in Formula (I), D, R, R, A, and Poly are as defined in the specification. 3. The compound according to or a pharmaceutically acceptable salt thereof claim 2 , wherein in Formula (I) or (II); R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , and Rare each independently a hydrogen atom; a substituted or unsubstituted linear or branched alkyl group having carbon number of 1 to 6; a substituted or unsubstituted cycloalkyl group having carbon number of 3 to 8; a substituted or unsubstituted linear or branched alkenyl group having carbon number of 2 to 6; a substituted or unsubstituted cycloalkenyl group having carbon number of 3 to 8; a substituted or unsubstituted linear or branched alkynyl group having carbon number of 2 to 6; a substituted or unsubstituted monocyclic or polycyclic aromatic group having carbon number of 6 to 14; or a substituted or unsubstituted 3- to 8-membered heterocyclic group containing at least one of a nitrogen atom claim 2 , an oxygen atom claim 2 , or a sulfur atom as a ring-constituting atom.4. The compound according to or a pharmaceutically acceptable salt thereof claim 2 , wherein in Formula (I) or (II) claim 2 , a substituent of alkyl claim 2 , a substituent of cycloalkyl group claim 2 , a substituent of alkenyl group claim 2 , a substituent of cycloalkenyl group claim 2 , a substituent of alkynyl group claim 2 , a substituent of aromatic group claim 2 , and a substituent of heterocyclic group in the groups represented by R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , and Rare groups selected from a hydroxyl group claim 2 , an alkyl group claim 2 , a cycloalkyl group claim 2 , an alkenyl group claim 2 , a cycloalkenyl group claim 2 , an alkynyl group claim 2 , a halogen atom claim 2 , an aromatic group claim 2 , a ...

CHONDROITIN SULPHATE PURIFICATION METHOD

The present invention relates to a downstream industrial method of purifying chondroitin sulphate obtained from animal cartilage, which produces a product fully compliant with the specifications required for the use of said compound in the pharmaceutical field. 1. A method for the separation of chondroitin sulphate (CS) and keratan sulphate (KS) from an aqueous solution containing them , comprisingadding to the aqueous solution a water-miscible organic solvent in conditions of ionic strength inducing formation of two liquid phases: a dense phase in which CS concentrates and a light phase in which KS concentrates.2. Method according to comprising:a) preparing an aqueous solution of CS/KS and determining its conductivity;b) optionally adding a salt able to dissociate in mono- or polyvalent ions to a pre-set conductivity value;c) gradually adding an amount of one or more water-miscible organic solvents so as to induce a phase separation with concentration of CS in the dense phase and KS in the light phase.3. Method according to wherein the water-miscible organic solvents are selected from methanol claim 1 , ethanol claim 1 , 1-propanol claim 1 , 2-propanol claim 1 , 1-butanol claim 1 , 2-butanol claim 1 , acetone claim 1 , acetonitrile or mixtures thereof.4. Method according to wherein the organic solvent is ethanol or 2-propanol.5. Method according to wherein the salt optionally added is sodium chloride.6. Method according to wherein the percentage by volume of each specific organic solvent is determined by a graph correlating said percentage to the measured conductivity value or to the concentration of the aqueous solution.7. Method according to wherein the dense phase containing CS is subjected to a further purification process.8. Method according to wherein the dense phase is diluted with water claim 7 , thereafter adding organic solvent until the re-formation of two liquid phases: a dense phase in which CS concentrates and a light phase in which KS concentrates.9. ...

USE OF LIPID CONJUGATES IN THE TREATMENT OF DISEASES

This invention provides compounds represented by the structure of the general formula (A): 2. The compound of claim 1 , wherein said lipid comprises a linear claim 1 , saturated claim 1 , mono-unsaturated claim 1 , or poly-unsaturated claim 1 , alkyl chain ranging in length from 2 to 30 carbon atoms.3. The compound of claim 2 , wherein said alkyl chain comprises a palmitic acid moiety or a myristic acid moiety.4. The compound of claim 1 , wherein X is a polysaccharide.5. The compound of claim 4 , wherein said polysaccharide is alginate.6. The compound of claim 1 , wherein Y is nothing.7. The compound of claim 1 , wherein any bond between L claim 1 , Z claim 1 , Y and X is either an amide or an esteric bond.8. The compound of claim 1 , wherein n is a number greater than 1.9. The compound of claim 1 , wherein n is a number from 1 to 500.10. The compound of claim 1 , wherein n is a number from 1 to 100. This application is a divisional application of U.S. application Ser. No. 13/739,207, filed Jan. 11, 2013, which is a divisional application of U.S. application Ser. No. 13/031,990, filed Feb. 22, 2011 now U.S. Pat. No. 8,383,787, which is a divisional application of U.S. application Ser. No. 12/010,315, filed Jan. 23, 2008, now U.S. Pat. No. 7,893,226, which is a divisional application of U.S. application Ser. No. 10/952,496, filed Sep. 29, 2004 now U.S. Pat. No. 7,393,938, which is a continuation-in-part application of U.S. application Ser. No. 09/756,765, filed Jan. 10, 2001, now U.S. Pat. No. 7,034,006, which claims priority to U.S. Provisional Application Nos. 60/174,905, filed Jan. 10, 2000 and 60/174,907, filed Jan. 10, 2000, which are hereby incorporated by reference in their entirety.This invention provides compounds represented by the structure of the general formula (A):wherein L is a lipid or a phospholipid, Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol, Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, X ...

CARBOHYDRATE CROSSLINKER

The invention relates to a hydrogel product comprising glycosaminoglycan molecules as the swellable polymer, wherein the glycosaminoglycan molecules are covalently crosslinked via crosslinks comprising a spacer group selected from the group consisting of di-, tri-, tetra-, and oligosaccharides. 1. A hydrogel product comprising glycosaminoglycan molecules as the swellable polymer , wherein the glycosaminoglycan molecules are covalently crosslinked via crosslinks consisting essentially of a spacer group selected from the group consisting of di- , tri- , tetra- , and oligosaccharides , wherein the crosslinked glycosaminoglycan molecules are preferably free , or essentially free from synthetic non-carbohydrate structures or linkers.2. A hydrogel product according to claim 1 , wherein the glycosaminoglycan molecules are hyaluronic acid.3. A hydrogel product according to claim 1 , wherein at least 75% of the crosslinks comprise a spacer group selected from the group consisting of di- claim 1 , tri- claim 1 , tetra- claim 1 , and oligosaccharides.4. A hydrogel product according to claim 1 , wherein the spacer group is a hyaluronic acid tetrasaccharide claim 1 , hyaluronic acid hexasaccharide claim 1 , trehalose claim 1 , lactose claim 1 , maltose claim 1 , sucrose claim 1 , cellobiose or raffinose residue.5. A hydrogel product according to claim 1 , wherein the spacer group is selected from the group consisting of di- claim 1 , tri- claim 1 , and tetrasaccharides.6. A hydrogel product according to claim 1 , wherein at least 90% of the bonds between glycosaminoglycan molecules and crosslinks are amide bonds.7. A hydrogel product according to claim 1 , wherein less than 5% of the bonds between glycosaminoglycan molecules and crosslinks are ester bonds.8. A hydrogel product according to claim 1 , in the form of an injectable formulation.9. A process of preparing a hydrogel product comprising crosslinked glycosaminoglycan molecules claim 1 , comprising the steps of:(a) ...

HYDROLYSIS OF ESTER BONDS IN AMIDE CROSSLINKED GLYCOSAMINOGLYCANS

A method of preparing a hydrogel product comprising crosslinked glycosaminoglycan molecules, said method including: i) providing a glycosaminoglycan crosslinked by amide bonds, wherein the crosslinked glycosaminoglycans include ester crosslinks formed as byproducts during the amide crosslinking; and ii) subjecting the crosslinked glycosaminoglycans to alkaline treatment to hydrolyze ester crosslinks formed as byproducts during the amide crosslinking. 1. A method of preparing a hydrogel product comprising crosslinked glycosaminoglycan molecules , said method comprising:i) providing a glycosaminoglycan crosslinked by amide bonds, wherein the crosslinked glycosaminoglycans comprise ester crosslinks formed as byproducts during the amide crosslinking; andii) subjecting the crosslinked glycosaminoglycans to alkaline treatment to hydrolyze ester crosslinks formed as byproducts during the amide crosslinking.2. A method according to claim 1 , wherein i) comprises the steps:a) providing a solution comprising glycosaminoglycans;b) activating carboxyl groups on the glycosaminoglycans with a coupling agent, to form activated glycosaminoglycans;c) crosslinking the activated glycosaminoglycans via their activated carboxyl groups using a di- or multiamine functional crosslinker to provide glycosaminoglycans crosslinked by amide bonds.3. A method according to claim 1 , wherein the glycosaminoglycan is selected from the group consisting of hyaluronic acid claim 1 , chondroitin and chondroitin sulfate claim 1 , and mixtures thereof.4. A method according to claim 1 , wherein i) comprises the steps:a) providing a solution comprising an at least partially deacetylated glycosaminoglycan and optionally a second glycosaminoglycan;b) activating carboxyl groups on the at least partially deacetylated glycosaminoglycan and/or the optional second glycosaminoglycan with a coupling agent, to form activated glycosaminoglycans;c) crosslinking the activated glycosaminoglycans via their activated ...

SHALE SWELLING INHIBITORS

The present invention provides amidic polymers, which exhibit shale swelling inhibitor activity having improved bio-degradability. The amidic polymers of the invention may be employed in a wide variety of compositions, particularly in subterranean drilling operations. Non-limiting generic structures of the amidic polymers are set out below: (1) wherein R-Rand integers m and n are defined herein. 113-. (canceled)14. An amidic polymer comprising a (a) polymer having a hydroxyl group reacted with a (c) vinyl amide to provide the amidic polymer.15. The amidic polymer according to claim 14 , wherein the (a) polymer having a hydroxyl group is selected from the group consisting of partially and fully hydrolyzed poly(vinyl alcohol)s claim 14 , polysaccharides claim 14 , and mixtures thereof.16. The amidic polymer according to claim 15 , wherein the polysaccharides are derived from celluloses claim 15 , hydroxyethyl celluloses claim 15 , carboxymethyl celluloses claim 15 , hydroxyethyl celluloses claim 15 , hydropropyl celluloses claim 15 , hydroxypropyl methyl celluloses claim 15 , ethyl celluloses claim 15 , carageenans claim 15 , chitosans claim 15 , chondroitin sulfates claim 15 , heparins claim 15 , hyaluronic acids claim 15 , starches claim 15 , chitins claim 15 , perctins claim 15 , guars claim 15 , xanthans claim 15 , dextrans claim 15 , welan gums claim 15 , gellan gums claim 15 , diutans claim 15 , pullulana claim 15 , and mixtures thereof.17. The amidic polymer according to claim 14 , wherein the (c) vinyl amide is selected from the group consisting of N-vinyl pyrrolidone; N-vinyl piperidone; N-vinyl caprolactam; N-vinyl-3-methyl pyrrolidone; N-vinyl-4-methyl pyrrolidone; N-vinyl-5-methyl pyrrolidone; N-vinyl-3-ethyl pyrrolidone; N-vinyl-3-butyl pyrrolidone; N-vinyl-3 claim 14 ,3-dimethyl pyrrolidone; N-vinyl-4 claim 14 ,5-dimethyl pyrrolidone; N-vinyl-5 claim 14 ,5-dimethyl pyrrolidone; N-vinyl-3 claim 14 ,3 claim 14 ,5-trimethyl pyrrolidone; N-vinyl-5-methyl-5- ...

Antiinfective composition

The present invention relates to the use of hydroxymethyl-group-containing glycosaminoglycans, such as in particular hydroxymethyl-hyaluronic acid, for the treatment and prevention of infectious diseases or malignant or premalignant diseases, in particular of the skin or mucosa. The invention additionally provides a preparation method for glycosaminoglycans modified with hydroxymethyl groups.

METHOD FOR PREPARING ACYLATED CROSSLINKED GLYCOSAMINOGLYCANS

A method of preparing a hydrogel product including crosslinked glycosaminoglycan molecules, said method including: i) providing a glycosaminoglycan crosslinked by amide bonds, wherein the crosslinked glycosaminoglycans include residual amine groups; and ii) acylating residual amine groups of the crosslinked glycosaminoglycans provided in i) to form acylated crosslinked glycosaminoglycans. 1. A method of preparing a hydrogel product comprising crosslinked glycosaminoglycan molecules , said method comprising:i) providing a glycosaminoglycan crosslinked by amide bonds, wherein the crosslinked glycosaminoglycans comprise residual amine groups; andii) acylating residual amine groups of the crosslinked glycosaminoglycans provided in i) to form acylated crosslinked glycosaminoglycans.2. A method according to claim 1 , wherein i) comprises the steps:a) providing a solution comprising an at least partially deacetylated glycosaminoglycan and optionally a second glycosaminoglycan;b) activating carboxyl groups on the at least partially deacetylated glycosaminoglycan and/or the optional second glycosaminoglycan with a coupling agent, to form activated glycosaminoglycans;c) crosslinking the activated glycosaminoglycans via their activated carboxyl groups using amino groups of the at least partially deacetylated glycosaminoglycans to provide glycosaminoglycans crosslinked by amide bonds.3. A method according to claim 2 , whereinthe at least partially deacetylated glycosaminoglycan is selected from the group consisting of deacetylated hyaluronic acid, deacetylated chondroitin and deacetylated chondroitin sulfate, and mixtures thereof.4. A method according to claim 2 , wherein the at least partially deacetylated glycosaminoglycan is deacetylated hyaluronic acid.5. A method according to claim 2 , wherein the at least partially deacetylated glycosaminoglycan has a degree of acetylation of 99% or less claim 2 , and a weight average molecular weight of 0.1 MDa or more.6. A method ...

TABLET WITH AN ANTIMYCOTIC AGENT, MEDICAL DEVICE AND METHOD FOR PRESERVING HARVESTED CORNEAS

A tablet containing at least amphotericin B deoxycholate, a substance with lubricating properties, a substance with disaggregating properties and a substance with aggregating properties, the tablet being usable in a device for preserving harvested corneas, in combination with a bottle () equipped with an openable and reclosable cap (), where the bottle contains a sterile preserving liquid () having a pH of between 7.2 and 7.6 and wherein the tablet can be completely dissolved; in accordance with the method claimed, a harvested cornea being preservable in the preserving liquid in which the tablet has been dissolved, for up to at least 15 days at a temperature of between 2° C. and 10° C. 126-. (canceled)27. A tablet containing at least amphotericin B deoxycholate , a substance with lubricating properties , a substance with disaggregating properties and a substance with aggregating properties.284. The tablet according to claim 27 , wherein the tablet () is soluble in liquids having a pH of between 7.2 and 7.6.29. The tablet according to claim 27 , wherein the substance with lubricating properties is L-Leucine.30. The tablet according to claim 27 , wherein the substance with disaggregating properties is mannitol.31. The tablet according to claim 27 , wherein the substance with aggregating properties is sorbitol.32. The tablet according to claim 27 , wherein the substance with disaggregating properties and the substance with aggregating properties are both constituted of isomalt.33. The tablet according to claim 27 , wherein:{'b': '4', 'the amphotericin B deoxycholate is present in a quantity by weight, relative to the total weight of the tablet (), of between 0.15% and 0.5%;'}{'b': '4', 'the substance with lubricating properties is present in a quantity by weight, relative to the total weight of the tablet (), of between 4% and 7%; and'}{'b': '4', 'the substance with disaggregating properties and the substance with aggregating properties are present as a whole in a ...

Chondroitin sulfate preparation process and equipment thereof

A chondroitin sulfate preparation process and device thereof and in particular a process for extracting ten thousand tons of chondroitin sulfate by means of a solvent-free process is disclosed. The process comprises steps such as liquefaction, extraction, enzymolysis and degradation, filtering, separation and after-treatment. The device comprises a reaction kettle. The reaction kettle is preferably a Teflon reaction kettle. The reaction kettle is in pipeline connection with a vacuum circulation filter, a filtrate storage tank and a molecular sieve in sequence. The molecular sieve is separately in pipeline connection with a protein fluid storage tank and a CS solution storage tank. The present invention has the advantages of low investment. Compared to the same production scale, the investment is cut by 80%. The larger the production scale is the more advantageous in investment. The production capacity is over million tons, which is unattainable by solvent-process technology. The production is automatic and continuous. The production quality is controllable. The CPC content is 60%-105% and other quality indexes meets or exceeds the current quality standard. The production is no pollution, zero discharge and environmentally friendly. 1: A chondroitin sulfate preparation method , comprising steps of: liquefying , extracting enzymolysis degradation , filtering , separating and providing after-treatment , wherein specifically:(1) liquefying: liquefying materials after steaming under a pressure to change the materials into liquid;(2) extracting enzymolysis degradation: cooling down a cartilage fluid liquidated in the step (1); adding an alkali for alkaline hydrolysis;adding an enzymolysis enzyme and a degradation enzyme for enzymolysis and degradation until the cartilage fluid disassociates into layers;(3) filtering: continuously filtering a mixed fluid produced in the step (2) by a filter device; producing a filtrate and cartilage residues; keeping a clarity of the ...

DERIVATIVES OF N-DESULFATED GLYCOSAMINOGLYCANS AND USE AS DRIGS

A glycosaminoglycan derivative which is obtainable by a process that includes the steps of N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan, and oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NHto aldehydes. The process further includes reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols, where the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof. 1. A glycosaminoglycan derivative which is obtainable by the following process:a) N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan;{'sub': '2', 'b) oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NHto aldehydes;'}c) reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols;wherein the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof.2. The glycosaminoglycan derivative of claim 1 , wherein the process further comprising:d) 2-O-desulfation of up to 50% of the 2-O-sulfated residues of the glycosaminoglycan, before or after N-desulfation.3. The glycosaminoglycan derivative of claim 2 , wherein said d) 2-O-desulfation of up to 25% of the 2-O-sulfated residues of the glycosaminoglycan.4. The glycosaminoglycan derivative of claim 1 , wherein the process further comprising:e) partial or total deacetylation of the N-acetylated residues of the glycosaminoglycan, before or ...

CROSSLINKED POLYMERIC NETWORK AND USE THEREOF

A packaging system for the storage of an ophthalmic device includes a sealed container containing one or more unused ophthalmic devices immersed in an aqueous packaging solution comprising one or more crosslinked polymeric networks. The one or more crosslinked polymeric network comprises a reaction product of a first glycosaminoglycan, a second glycosaminoglycan, and a first crosslinking agent, wherein the first glycosaminoglycan is different than the second glycosaminoglycan. The aqueous packaging solution has an osmolality of at least about 180 mOsm/kg, a pH of about 6 to about 9 and is heat sterilized 1. A packaging system for the storage of an ophthalmic device comprising a sealed container containing one or more unused ophthalmic devices immersed in an aqueous packaging solution comprising one or more crosslinked polymeric networks , wherein the one or more crosslinked polymeric network comprises a reaction product of a first glycosaminoglycan , a second glycosaminoglycan , and a first crosslinking agent , wherein the first glycosaminoglycan is different than the second glycosaminoglycan , and wherein the aqueous packaging solution has an osmolality of at least about 180 mOsm/kg , a pH of about 6 to about 9 and is heat sterilized.2. The packaging system of claim 1 , wherein the first glycosaminoglycan and the second glycosaminoglycan are independently selected from the group consisting of chondroitin claim 1 , chondroitin sulfate claim 1 , dermatan claim 1 , dermatan sulfate claim 1 , heparin claim 1 , heparan sulfate claim 1 , hyaluronan claim 1 , hyaluronic acid claim 1 , sucrose claim 1 , lactulose claim 1 , lactose claim 1 , maltose claim 1 , trehalose claim 1 , cellobiose claim 1 , mannobiose and chitobiose.3. The packaging system of claim 1 , wherein the first glycosaminoglycan is hyaluronic acid and the second glycosaminoglycan is chondroitin sulfate.5. The packaging system of claim 4 , wherein GAG is hyaluronic acid and GAG′ is chondroitin sulfate.7. ...

METHOD FOR PRODUCING SUGAR HAVING SULFATE GROUP AND/OR PHOSPHATE GROUP

An object of the invention is to provide a method of uniformly and efficiently producing a saccharide having a sulfate group and/or a phosphate group in the molecule, or a compound containing the saccharide. [Solution] The present invention provides a method of producing a saccharide having a sulfate group and/or a phosphate group. The method comprises (a) a step of preparing a “first saccharide having a non-protected sulfate group and/or a non-protected phosphate group” and a “second saccharide having a non-protected sulfate group and/or a non-protected phosphate group” and (b) a step of condensing the first saccharide and the second saccharide prepared in the step (a) with each other. 1. A method of producing a saccharide having a sulfate group and/or a phosphate group , comprising:(a) a step of preparing a first saccharide having a non-protected sulfate group and/or a non-protected phosphate group and a second saccharide having a non-protected sulfate group and/or a non-protected phosphate group and(b) a step of condensing the first saccharide and the second saccharide prepared in the step (a) with each other.2. The production method according to claim 1 , wherein the first saccharide and the second saccharide are each a saccharide having a leaving group at a 1-position carbon atom of the saccharide and having a nucleophilic group.3. The production method according to claim 1 , wherein the first saccharide and the second saccharide are the same saccharide.4. The production method according to claim 2 , wherein the nucleophilic group is selected from a hydroxy group claim 2 , an amino group claim 2 , and a thiol group.5. The production method according to claim 1 , wherein the first saccharide and the second saccharide are each a saccharide constituting a 6-membered ring claim 1 , and have a leaving group at a 1-position carbon atom of the saccharide claim 1 , a nucleophilic group at least at any of positions 2 claim 1 , 3 claim 1 , 4 claim 1 , or 6 of the ...

CHELATOR-FUNCTIONALIZED GLYCOSAMINOGLYCANS

A compound includes a polysaccharide moiety and one or more chelating agents. The one or more chelating agents are covalently bonded to the polysaccharide moiety. The polysaccharide moiety can include a glycosaminoglycan moiety, such as a hyaluronic acid polymer or a sulfated glycosaminoglycan moiety. The compound can be used to treat or prevent a disease or disorder in a patient with a metal implant. The compound reduces a concentration of metal particulates or metal ions in the subject. 1. A compound , comprising a polysaccharide moiety and one or more chelating agents.2. The compound of claim 1 , wherein the one or more chelating agents are covalently bonded to the polysaccharide moiety.3. The compound of claim 1 , wherein each of the chelating agents is independently a chelator of one or more metals selected from the group consisting of As claim 1 , Hg claim 1 , Au claim 1 , Pb claim 1 , Co claim 1 , Ni claim 1 , Cr claim 1 , Ti claim 1 , Ta claim 1 , Cu claim 1 , Fe claim 1 , Mo claim 1 , and Gd.4. The compound of claim 1 , wherein each of the chelating agents is independently a chelator of one or more metals selected from the group consisting of Co claim 1 , Ni claim 1 , and Cr.5. The compound of claim 1 , wherein each of the chelating agents is independently selected from the group consisting of British anti-Lewisite (BAL) dimercaprol claim 1 , ethylene diamine tetra-acetic acid (EDTA) claim 1 , N-acetyl-cysteine (NAC) claim 1 , D-penicillamine claim 1 , 1 claim 1 ,4 claim 1 ,7-triazacyclononanetriacetic acid (NOTA) claim 1 , 1 claim 1 ,4 claim 1 ,7 claim 1 ,10-tetraazacyclododecane-1 claim 1 ,4 claim 1 ,7 claim 1 ,10-tetraacetic acid (DOTA) claim 1 , 1 claim 1 ,4 claim 1 ,7-triazacyclononane-1-glutaric acid-4 claim 1 ,7-diacetic acid (NODAGA) claim 1 , diethylene triaminepentaacetic acid (DTPA) claim 1 , cyclohexyl-1 claim 1 ,2-diaminetetraacetic acid (CDTA) claim 1 , ethyleneglycol-O claim 1 ,O′-bis(2-aminoethyl)-N claim 1 ,N claim 1 ,N′ claim 1 ,N′- ...

Low-Molecular-Weight Biotechnological Chondroitin 6-Sulphate for Prevention of Osteoarthritis

Disclosed is a low-molecular-weight (1000-5000 daltons) chondroitin sulphate (CS) produced by chemical sulphation and subsequent depolymerisation of a non-sulphated chondroitin backbone obtained with biotechnology techniques. The CS described is substantially monosulphated, mainly at the 6-position, with very little sulphation at the 4-position, and with a mono/disulphated disaccharide ratio and charge density similar to those of natural CS. Said biotechnological chondroitin 6-sulphate (C6S) is useful in the treatment and prevention of osteoarthritis and in acute and chronic inflammatory processes. 1. A chondroitin sulphate having a molecular weight ranging from 1000 to 5000 daltons having anti-inflammatory and anti-arthritic biological activity comprising at least about 65% by weight disaccharide 6-monosulphate , less than about 1% by weight disaccharide 4-monosulphate , about 20% by weight or less disaccharide 2 ,6-disulphate , less than about 5% by weight disaccharide 4 ,6-disulphate , less than about 1% by weight disaccharide 2 ,4-disulphate , less than about 15% by weight non-sulphated disaccharide , and a charge density value ranging from about 1 to about 1.25.2E. coli. A chondroitin sulphate according to claim 1 , wherein said chondroitin sulphate is obtained by chemical sulphation and subsequent acid or radical depolymerisation of the capsular polysaccharide K4 of after removal of the fructose residues by means of hydrolysis.3E. coli. A chondroitin sulphate according to claim 1 , wherein said chondroitin sulphate is obtained by chemical sulphation of the low-molecular-weight natural fraction of the capsular polysaccharide K4 of carried out after removal of the fructose residues by means of hydrolysis.4E. coli. A chondroitin sulphate according to claim 1 , wherein said chondroitin sulphate is obtained by chemical sulphation and subsequent acid or radical depolymerisation of the capsular polysaccharide originally free from fructose residues (K4-d) claim 1 , ...

METHOD FOR SULFATING GLYCOSAMINOGLYCAN

An object of the present invention is provide a method for sulfating a glycosaminoglycan in a solution of a non-organic solvent. In the present invention, sulfation reaction of a glycosaminoglycan is performed with a sulfating agent in a strongly basic solution of a non-organic solvent. In the present invention, pH of the strongly basic solution is preferably set to be 11.5 or higher. According to the present invention, for example, a glycosaminoglycan having heparin-like anticoagulant activity can be produced from N-acetylheparosan through one-pot procedure. In one embodiment, a sulfated glycosaminoglycan produced by the method of the present invention has a unique disaccharide composition and is expected to be a novel useful material. 1. A method for sulfating a glycosaminoglycan , the method comprising performing sulfation reaction in a strongly basic solution under coexistence of a glycosaminoglycan with a sulfating agent.2. The method according to claim 1 , wherein pH of the strongly basic solution is set to be 11.5 or higher.3. The method according to claim 1 , wherein the glycosaminoglycan is selected from among the following glycosaminoglycans (A) to (D):(A) a glycosaminoglycan having a hexuronic acid residue;(B) a glycosaminoglycan prepared through addition or elimination of a substituent or a functional group to or from the glycosaminoglycan (A);(C) a glycosaminoglycan prepared through deacetylation of the glycosaminoglycan (A); and(D) a glycosaminoglycan prepared through alkylation of the glycosaminoglycan (A).4. A method for producing a sulfated glycosaminoglycan claim 1 , the method comprising a step of performing a method as recited in .5. The method according to claim 4 , the method further comprising a step of performing deacetylation reaction of the glycosaminoglycan.6. The method according to claim 4 , the method further comprising a step of performing alkylation reaction of the glycosaminoglycan.712-. (canceled)13. The method according to claim 4 ...

CHONDROITIN SULFATE POLYSACCHARIDE, AND SEMI-SYNTHETIC PREPARATION METHOD THEREFOR AND USE THEREOF

The present invention relates to the technical field of medicine, in particular to a chondroitin sulfate polysaccharide, and a semi-synthetic preparation method therefor and the use thereof. A metal salt of the chondroitin sulfate polysaccharide provided by the present invention has an anti-inflammatory effect, and can be used for preparing a drug against inflammatory diseases. In particular, the metal salt of the chondroitin sulfate polysaccharide provided by the present invention has anti-inflammatory and bone-protecting effects, and can be used for preparing a drug against rheumatoid arthritis and for preparing a drug against osteoarthritis. The present invention provides a method for preparing the metal salt of the chondroitin sulfate polysaccharide, and the metal salt of the chondroitin sulfate polysaccharide with different degrees of sulfation can be obtained by semi-synthetic means in the present invention. The method is simple to operate and suitable for large-scale production. 2. The metal salt of chondroitin sulfate glycan according to claim 1 , wherein the chondroitin sulfate glycan anion has an average molecular weight in a range of from 4 claim 1 ,000 Da to 15 claim 1 ,000 Da; and the chondroitin sulfate glycan anion has a molor ratio of —SO to —COOin a range of from 1.9 to 2.5.3. The metal salt of chondroitin sulfate glycan according to claim 1 , wherein the metal cation comprises a sodium ion and/or a calcium ion and/or a potassium ion.4. A method for preparation of the metal salt of chondroitin sulfate glycan according to claim 1 , comprising steps of:mixing a raw material of chondroitin sulfate glycan, a sulfating reagent, and an organic solvent for sulfation to provide a sulfation product system; andsubjecting the sulfation product system successively to a first precipitating treatment, salification treatment, dialysis, a second precipitating treatment, and gel column purification to provide the metal salt of chondroitin sulfate glycan, wherein a ...

HYBRID COOPERATIVE COMPLEXES OF HYALURONIC ACID

Describes cooperative hybrid complexes of hyaluronic acid, a simple and economical method for production thereof and use thereof in the area of medicine, cosmetics and food. 123-. (canceled)24. A method of preparing stable , hybrid cooperative L/H-HA complexes with the method comprising:{'sup': 4', '6, 'sub': H-HA', 'MWL-HA, 'submitting to thermal treatment, at temperature comprised between 80° and 160°, solutions containing simultaneously L-HA hyaluronic acid or hyaluronans and H-HA hyaluronic acid or hyaluronans wherein the molecular weight of L-HA is comprised between 1×10to 1×10Da and that of H-HA is given by the formula MW≧/0.9.'}25. The method according to wherein said temperature is comprised between 100° and 120° C.26. The method according to claim 24 , wherein H-HA and L-HA are present in relative quantities comprised between 0.1 and 10.27. The method according to wherein said L/H-HA complexes have a viscosity from 1.1 to 200-fold less than that of a solution containing the H-HA hyaluronic acid alone used for forming the complex.28. The method according to claim 27 , wherein other chemical species in addition to solvent and hyaluronic acid are also present in the solution.29. The method according to claim 24 , wherein the solvent used is water.30. The method according to claim 24 , wherein the thermal treatment is carried out in autoclave.31. The method according to claim 24 , wherein the thermal treatment includes keeping the sample at the maximal temperature for times which are from 10 seconds to 2 hrs.32. The method according to claim 31 , wherein the thermal treatment includes reaching the maximal temperature over times from 1 min to 1 h.33. The method according to wherein the thermal treatment includes cooling the solution claim 31 , after exposure at the maximal temperature claim 31 , over times from 1 min to 1 h.34. The method according to claim 24 , wherein said L/H-HA complexes are prepared in the solid state by precipitation of the solutions ...

BIOTECHNOLOGICAL SULPHATED CHONDROITIN SULPHATE AT POSITION 4 OR 6 ON THE SAME POLYSACCHARIDE CHAIN, AND PROCESS FOR THE PREPARATION THEREOF

The present invention discloses a process for the production of chondroitin sulphate with an average molecular weight (Mw) of 10-30 kDa by chemical sulphation starting from an unsulphated chondroitin backbone, obtained in turn by acid hydrolysis of capsular polysaccharide K4 made directly from strain O5:K4:H4, or directly produced from a genetically modified strain of . Sulphation of the N-acetyl-D-galactosamine residue at position 4 or 6 takes place simultaneously in the same polysaccharide chain, simulating the sulphation pattern observed in natural chondroitin sulphate, unlike the sulphation obtained with the synthesis methods described to date. 2E. ColiE. Coli. The process of wherein the chondroitin sodium salt of step a) is obtained starting either from the capsular polysaccharide K4 produced by a culture broth of strain O5:K4:H4 claim 1 , or from the polysaccharide produced by a culture broth of strain DSM23644.3. The process of wherein step b) is carried out with an orthoester selected from trimethyl orthoacetate claim 1 , triethyl orthoacetate claim 1 , trimethyl orthoformate claim 1 , triethyl orthoformate claim 1 , trimethyl orthopropionate claim 1 , triethyl orthopropionate or trimethyl orthobenzoate.4. The process of wherein the acid catalysis of step b) is carried out with an acid selected from camphorsulphonic acid claim 1 , para-toluenesulphonic acid claim 1 , methanesulphonic acid or a sulphone resin.5. The process of wherein step c) is effected with acetic anhydride.6. The process of wherein step d) is effected from about 20° C. to about 40° C.7. The process of wherein step d) is effected from about 40° C. to about 70° C.8. The process of wherein step d) is effected in a water/organic water-soluble acid mixture or in water alone.9. The process of claim 8 , wherein the organic acid is selected from acetic claim 8 , formic claim 8 , propionic claim 8 , tartaric claim 8 , citric acid or a propionic resin.10. The process of wherein the obtained ...

METHOD FOR DEACETYLATION OF BIOPOLYMERS

A method for at least partial deacetylation of a biopolymer comprising acetyl groups, including: a1) providing a biopolymer including acetyl groups; a2) reacting the biopolymer including acetyl groups with hydroxylamine (NHOH) or a salt thereof at a temperature of 100° C. or less for 2-200 hours to form an at least partially deacetylated biopolymer; and a3) recovering the at least partially deacetylated biopolymer. 117.-. (canceled)18. A method of preparing a hydrogel product comprising crosslinked glycosaminoglycan molecules , the method comprising:(a) deacetylating glycosaminoglycans using a hydroxylamine or salt thereof to produce at least partially deacetylated glycosaminoglycans;(b) crosslinking the at least partially deacetylated glycosaminoglycans using a crosslinker, wherein the crosslinking comprises forming amide bonds between activated carboxyl groups of the at least partially deacetylated glycosaminoglycans and nucleophiles on the crosslinker, wherein the crosslinked at least partially deacetylated glycosaminoglycans comprise residual amine groups;(c) re-acylating the crosslinked at least partially deacetylated glycosaminoglycans.19. The method of claim 18 , wherein:the crosslinked at least partially deacetylated glycosaminoglycans comprise ester crosslinks; andthe method further comprises (d) subjecting the re-acylated crosslinked glycosaminoglycans to alkaline treatment to hydrolyze the ester crosslinks.20. The method of claim 18 , wherein the activated carboxyl groups of the at least partially deacetylated glycosaminoglycans in (b) are obtained by: activating carboxyl groups on the at least partially deacetylated glycosaminoglycan with a coupling agent.21. The method of claim 18 , wherein the glycosaminoglycan is selected from the group consisting of hyaluronic acid claim 18 , chondroitin claim 18 , chondroitin sulfate claim 18 , and mixtures thereof.22. The method of claim 18 , wherein the deacetylating in (a) is performed using a hydroxylamine salt ...

METHOD FOR DEACETYLATION OF BIOPOLYMERS

A method for at least partial deacetylation of a biopolymer comprising acetyl groups, including: a1) providing a biopolymer including acetyl groups; a2) reacting the biopolymer including acetyl groups with hydroxylamine (NHOH) or a salt thereof at a temperature of 100° C. or less for 2-200 hours to form an at least partially deacetylated biopolymer; and a3) recovering the at least partially deacetylated biopolymer. 1. A method of preparing a hydrogel product comprising crosslinked glycosaminoglycan molecules , the method comprising:(a) obtaining a solution comprising an at least first glycosaminoglycan that is a partially deacetylated glycosaminoglycan with a degree of acetylation between 50% and 99% and a second glycosaminoglycan, wherein the second glycosaminoglycan is different from the at least partially deacetylated glycosaminoglycan;(b) activating carboxyl groups on the at least partially deacetylated glycosaminoglycan and/or the second glycosaminoglycan with a coupling agent, to form activated glycosaminoglycans;(c) crosslinking the activated glycosaminoglycans using a crosslinker comprising at least two amine groups solely with amide bonds to provide crosslinked glycosaminoglycans; and(d) acylating residual amine groups of the crosslinked glycosaminoglycans obtained in (c) to form acylated crosslinked glycosaminoglycans; and(e) subjecting the crosslinked glycosaminoglycans provided in (c) or (d) to alkaline treatment to hydrolyze ester crosslinks formed as byproducts during the amide crosslinking in (c),wherein the first and second glycosaminoglycans are not the crosslinker, and wherein the crosslinker comprises a di-, tri-, or tetra-saccharide, oligosaccharide, or polysaccharide.2. The method according to claim 1 , wherein the second glycosaminoglycan is at least partially deacetylated.3. The method according to claim 1 , wherein at least 1% of N-acetyl groups of the first glycosaminoglycan have been converted to free amine groups.4. The method according to ...

GLYCOSAMINOGLYCAN ESTERS, PROCESSES FOR THEIR PREPARATION AND THEIR USE IN FORMULATIONS FOR OPHTHALMIC USE

Glycosaminoglycan esters, wherein at least part of the hydroxyl groups present on the N-acetylglucosamine residue are esterified with an apocarotenoid, their preparation, and their use in formulations for ophthalmic use are described. 1. Glycosaminoglycan esters , wherein at least part of the hydroxyl groups present on the N-acetylglucosamine residue are esterified with an apocarotenoid , wherein said apocarotenoid is not retinoic acid.2. Esters according to claim 1 , wherein said glycosaminoglycans are selected from: hyaluronic acid claim 1 , chondroitin sulfate claim 1 , heparin claim 1 , heparan sulfate.3. Esters according to claim 1 , wherein said apocarotenoids are selected from: crocetin claim 1 , bixin claim 1 , abscisic acid.4. Esters according to claim 1 , wherein the degree of substitution of apocarotenoid in the esters is from 0.1 to 5% and the molecular weight of said esters is from 350 claim 1 ,000 to 2 claim 1 ,000 claim 1 ,000 Daltons.5. A process for preparing esters according to claim 1 , wherein:a hyaluronic acid tetrabutylammonium salt is first prepared by salifying an ionic exchange resin with an aqueous solution of tetrabutylammonium hydroxide;the resin is washed with water and a solution of sodium hyaluronate dissolved in water is passed therethrough, thus collecting the eluate and freeze-drying it;the thus-obtained salt is reacted under heating with the selected apocarotenoid, the carboxy functionality of which is activated by reaction at room temperature with carbonyldiimidazole in dimethylformamide;the mixture is left under stirring, then the product is precipitated by the addition of sodium chloride and ethanol.6. A method for protecting eyes of an individual from blue light comprising:administrating to the eyes of the individual an effective amount of glycosaminoglycan esters, wherein at least a part of the hydroxyl groups present on the N-acetylglucosamine residue are esterified with an apocarotenoid.7. The method according to claim 6 , ...

DEGRADABLE THIOL-ENE POLYMERS AND METHODS OF MAKING THEREOF

Provided are methods for linking polypeptides (including peptides and proteins) to other moieties using radical imitated thiol-ene chemistries, for example, modifying a polypeptide by introducing reactive thiol groups and reacting the thiol groups with olefin-containing reagents or alkyne-containing reagents under conditions that support radical thiol-ene or thiol-yne reactions. The reactive thiol groups have greater activity for radical thiol-ene reactions that a cysteine thiol group, including thiol groups that are separated from the peptide backbone by at least two carbon atoms, for example, the thiol group of a homocysteine residue. Also provided are compositions and biomaterials containing the linked polypeptides, for example, peptide and protein conjugates, and thiol-ene based biocompatible hydrogel polymers, and their uses in the medical field. 1. A method for selectively linking a polypeptide in the presence of one or more cysteine residues ,wherein the polypeptide comprises a peptide backbone comprising a homocysteine residue having a reactive thiol group or a 2-amino-5-mercaptopentanoic acid residue having a reactive thiol group,wherein the method comprises reacting the reactive thiol group of the homocysteine residue or the 2-amino-5-mercaptopentanoic acid residue of the polypeptide with an ene compound comprising one or more reactive ene groups under conditions that promote a radical-mediated thiol-ene reaction.2. The method according to claim 1 , wherein the radical-mediated thiol-ene reaction is initiated with a radical initiator.3. (canceled)4. The method according to claim 1 , wherein the polypeptide comprises a homocysteine residue.5. (canceled)6. The method according to claim 2 , wherein the radical initiator is a photoinitiator selected from the group consisting of lithium phenyl-2 claim 2 ,4 claim 2 ,6-trimethylbenzoylphosphinate (LAP) claim 2 , sodium phenyl-2 claim 2 ,4 claim 2 ,6-trimethylbenzoylphosphinate (NAP) claim 2 , 2-hydroxy-1-[4-(2- ...

METHOD FOR IN VIVO PRODUCTION OF GLYCOSAMINOGLYCANS

The present invention relates to a method for in vivo production of glycosaminoglycans (GAG), by metabolic engineering in a genetically modified cell. In a method according to the invention, said cell is genetically modified in order to express the genes coding for the enzymes that are suitable for synthesising GAG from an exogenous precursor, preferably internalised by the cell. According to one specific feature, the present invention relates to a method for producing chondroitin or heparosan in a genetically modified bacterial cell, from an exogenous beta-galactoside precursor, preferably internalised by the cell. According to another specific feature, the present invention relates to the use of an cell comprising at least the genes glcA-T, kfoC, kfiD and wbpP for the production of chondroitin. According to yet another specific feature, the present invention relates to the use of an cell comprising at least the genes glcA-T, kfiA, kfiB, kfiC and kfiD for the production of heparosan. The present invention also relates to the use of the obtained glycosaminoglycans by implementing a method according to the invention in order to prepare a drug, a food composition or a cosmetic product. 1. Method for producing glycosaminoglycan (GAG) in a genetically modified cell , said method comprising the following steps: an exogenous gene encoding an enzyme capable of exerting a glycosyltransferase activity on a beta-galactoside substrate, and the elements enabling the expression of said gene in said cell and the synthesis of glycosyl beta-galactoside,', 'a gene encoding an enzyme capable of synthesizing said glycosaminoglycan from glycosyl beta-galactoside, or the genes encoding the enzymes of the synthetic pathway of said glycosaminoglycan from glycosyl beta-galactoside, and the elements enabling the expression of said gene(s) in said cell,', 'a gene encoding an enzyme capable of ensuring the internalization by the cell of exogenous beta-galactoside, and the elements enabling ...

Compositions and Methods for Treating a Disorder or Defect in Soft Tissue

The present invention encompasses methods and compositions for generating a biomimetic proteoglycan. The invention includes methods of treating a disease, disorder, or condition of soft tissue using a biomimetic proteoglycan. 1. A method of generating a biomimetic proteoglycan , said method comprising attaching a glycosaminoglycan (GAG) to a core structure.2. The method of claim 1 , wherein said GAG is selected from the group consisting of hyaluronic acid claim 1 , chondroitin claim 1 , chondroitin sulfate claim 1 , heparin claim 1 , heparin sulfate claim 1 , dermatin claim 1 , dermatin sulfate claim 1 , laminin claim 1 , keratan sulfate claim 1 , chitin claim 1 , chitosan claim 1 , acetyl-glucosamine claim 1 , oligosaccharides claim 1 , and any combination thereof.3. The method of claim 1 , wherein said core structure is selected from the group consisting of a synthetic polymer claim 1 , a protein claim 1 , a peptide claim 1 , a nucleic acid claim 1 , a carbohydrate claim 1 , and any combination thereof.4. The method of claim 1 , wherein said core structure is a synthetic polymer selected from the group consisting poly(4-vinylphenyl boronic acid) claim 1 , poly (3 claim 1 ,3′-diethoxypropyl methacylate) claim 1 , polyacrolein claim 1 , poly(N-isopropyl acrylaminde-co-glycidyl methacrylate) claim 1 , poly(allyl glycidyl ether) claim 1 , poly(ethylene glycol) claim 1 , poly(acrylic acid) claim 1 , and any combination thereof.5. The method of claim 1 , wherein said GAG comprises a terminal handle selected from the group consisting of a terminal primary amine claim 1 , terminal diol claim 1 , and an introduced aldehyde.6. The method of claim 1 , wherein said GAG is attached to said core structure by way of a linking chemistry selected from the group consisting of a bornic acid-diol linkage claim 1 , epoxide-amin linkage claim 1 , aldehyde-amine linkage claim 1 , carboxylic acid-amine linkage claim 1 , sulfhydryl-maleimide linkage claim 1 , and any combination thereof.7 ...

Low-Molecular-Weight Biotechnological Chondroitin 6-Sulphate for Prevention of Osteoarthritis

Disclosed is a low-molecular-weight (1000-5000 daltons) chondroitin sulphate (CS) produced by chemical sulphation and subsequent depolymerisation of a non-sulphated chondroitin backbone obtained with biotechnology techniques. The CS described is substantially monosulphated, mainly at the 6-position, with very little sulphation at the 4-position, and with a mono/disulphated disaccharide ratio and charge density similar to those of natural CS. Said biotechnological chondroitin 6-sulphate (C6S) is useful in the treatment and prevention of osteoarthritis and in acute and chronic inflammatory processes. 1. A chondroitin sulphate having a molecular weight ranging from 1000 to 5000 daltons having anti-inflammatory and anti-arthritic biological activity comprising at least about 65% by weight disaccharide 6-monosulphate , less than about 1% by weight disaccharide 4-monosulphate , about 20% by weight or less disaccharide 2 ,6-disulphate , less than about 5% by weight disaccharide 4 ,6-disulphate , less than about 1% by weight disaccharide 2 ,4-disulphate , less than about 15% by weight non-sulphated disaccharide , and a charge density value ranging from about 1 to about 1.25.2E. coli. A chondroitin sulphate according to claim wherein said chondroitin sulphate is obtained by chemical sulphation and subsequent acid or radical depolymerisation of the capsular polysaccharide K4 of after removal of the fructose residues by means of hydrolysis.3E. coli. A chondroitin sulphate according to claim 1 , wherein said chondroitin sulphate is obtained by chemical sulphation of the low-molecular-weight natural fraction of the capsular polysaccharide K4 of carried out after removal of the fructose residues by means of hydrolysis.4E. coli. A chondroitin sulphate according to claim 1 , wherein said chondroitin sulphate is obtained by chemical sulphation and subsequent acid or radical depolymerisation of the capsular polysaccharide originally free from fructose residues (K4-d) claim 1 , ...

Glycosaminoglycan derivative and method for producing same

The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance.

TERTIARY AMINE COMPOUND OR IMINE COMPOUND-POLYMER CONJUGATE AND PRODUCTION METHOD THEREFOR

Provided is a compound obtained by conjugating a tertiary amine compound or imine compound, which is useful as a drug, with a polymer, in which a structure D having a quaternary ammonium salt or iminium salt formed from a tertiary amine compound or imine compound D and a polymer residue Poly having a carboxy group are bonded to each other via a structure —C(R)(R)OC(O)ANHC(═O)—. 3. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein in Formula (I) or (II); R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare each independently a hydrogen atom; a substituted or unsubstituted linear or branched chain alkyl group having carbon number of 1 to 6; a substituted or unsubstituted cycloalkyl group having carbon number of 3 to 8; a substituted or unsubstituted linear or branched alkenyl group having carbon number of 2 to 6; a substituted or unsubstituted cycloalkenyl group having carbon number of 3 to 8; a substituted or unsubstituted linear or branched alkynyl group having carbon number of 2 to 6; a substituted or unsubstituted monocyclic or polycyclic aromatic group having carbon number of 6 to 14; or a substituted or unsubstituted 3- to 8-membered heterocyclic group containing at least one of a nitrogen atom claim 1 , an oxygen atom claim 1 , or a sulfur atom as a ring-constituting atom.4. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein in Formula (I) or (II) claim 1 , a substituent of alkyl claim 1 , a substituent of cycloalkyl group claim 1 , a substituent of alkenyl group claim 1 , a substituent of cycloalkenyl group claim 1 , a substituent of alkynyl group claim 1 , a substituent of aromatic group claim 1 , and a substituent of heterocyclic group in the groups represented by R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare groups selected from a hydroxyl group claim 1 , an alkyl group claim 1 , a cycloalkyl group claim 1 , an alkenyl group claim 1 , a ...

HYALURONIC ACID-BINDING SYNTHETIC PEPTIDOGLYCANS, PREPARATION, AND METHODS OF USE

This invention pertains to the field of hyaluronic acid-binding synthetic peptidoglycans and methods of forming and using the same. 1. A synthetic peptidoglycan comprising a synthetic peptide covalently conjugated to a glycan wherein the synthetic peptide comprises a hyaluronic acid-binding sequence.2. The synthetic peptidoglycan of wherein the synthetic peptide comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 claim 1 ,wherein X8 is present or is not present,wherein B1 is a basic amino acid,wherein B2 is a basic amino acid, andwherein X1-X8 are non-acidic amino acids.4. The synthetic peptidoglycan of wherein the glycan is selected from the group consisting of dextran claim 1 , chondroitin claim 1 , chondroitin sulfate claim 1 , dermatan claim 1 , dermatan sulfate claim 1 , heparan claim 1 , heparin claim 1 , keratin claim 1 , keratan sulfate claim 1 , and hyaluronic acid.5. The synthetic peptidoglycan of wherein the synthetic peptidoglycan is resistant to aggrecanase.6. The synthetic peptidoglycan of wherein the peptide component of the synthetic peptidoglycan has a glycine-cysteine attached to the C-terminus of the peptide.7. An engineered collagen matrix comprising polymerized collagen claim 1 , hyaluronic acid claim 1 , and a hyaluronic acid-binding synthetic peptidoglycan comprising a peptide component and a glycan component.8. The engineered collagen matrix of wherein the peptide component of the synthetic peptidoglycan comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 claim 7 ,wherein X8 is present or is not present,wherein B1 is a basic amino acid,wherein B2 is a basic amino acid, andwherein X1-X8 are non-acidic amino acids.10. The engineered collagen matrix of wherein the glycan component of the synthetic peptidoglycan is selected from the group consisting of dextran claim 7 , chondroitin claim 7 , chondroitin sulfate claim 7 , dermatan claim 7 , dermatan sulfate claim 7 , heparan claim 7 , heparin ...

GLYCOSAMINOGLYCAN DERIVATIVE AND METHOD FOR PRODUCING SAME

The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance. 14.-. (canceled)5. A method for suppressing pain , the method comprising administering a pharmaceutical composition to a living body ,wherein the pharmaceutical composition comprises a chondroitin sulfate derivative,wherein the chondroitin sulfate derivative comprises a group derived from a chondroitin sulfate, a group derived from a steroid, and a spacer which couples the group derived from the chondroitin sulfate to the group derived from the steroid by a covalent bond,wherein the group derived from the steroid and the spacer are covalently bonded through an ester bond,wherein the group derived from chondroitin sulfate and the spacer are covalently bonded through an amide bond,wherein a molecule for forming the spacer has a coupling group which may have one or more substituent and couples the ester bond and the amide bond, and the length of the coupling group between the ester bond and the amide bond is 2 to 12 atoms, andwherein a dissociation rate of the steroid from the chondroitin sulfate derivative is 0.1 to 10%/day in a phosphate buffered saline with pH of 7.5 at 36° C., andwherein the pharmaceutical composition is administered locally.6. A method for obtaining anti-inflammatory effect , the method comprising administering a pharmaceutical composition to a living body ,wherein the pharmaceutical composition comprises a chondroitin sulfate derivative,wherein the chondroitin sulfate derivative comprises a group derived from a chondroitin sulfate, a group derived from a steroid, and a spacer which couples the group derived ...

Conjugate of a fragment of a cellular wall of a bacterium and a mucopolysaccharidic carrier, and uses in medicine thereof

The present invention relates in one aspect to a conjugate of a mucopolysaccharide or mucopolysaccharidic fraction and a cellular wall fragment of a bacterium belonging to the Corynebacterium genus, and in particular to the Corynebacterium granulosum species, also named P40. The conjugate of the invention is applied to medicine, in particular for topical treatment of infections, dermatological affections, such as psoriasis, acne, allergic reactions, such as rashes and eczema, and in vaginal mucosae affections.

Derivatives of Sulfated Polysaccharides, Method of Preparation, Modification and Use Thereof

The invention relates to the preparation and the use of α,β-unsaturated aldehydes in the structure of sulfated polysaccharides. It concerns the derivatives with a conjugated double bond in the 4th and 5th positions of the galactopyranose part situated in the 6th position with respect to the aldehyde, according to the general structural formula (I) or its hydrated form according to the general structural formula (II). The preparation of these derivatives derives from sulfated polysaccharides containing a galactopyranose ring sulfated in the 4th position that is bound in the polymer chain via α(1→3) or β(1→3) O-glycosidic bond. In the described solution, the sulfated polysaccharides undergo a regio- and chemoselective oxidation to form C6-saturated aldehyde, which, via a direct elimination of the sulfate group, provides the α,β-unsaturated derivative according to the general formula (I) or (II). The described solution is technically advantageous, because it leads directly to α,β-unsaturated aldehydes, without any elimination agents, higher temperature, or isolation of intermediates during the synthesis. The conjugation in the structure of α,β-unsaturated aldehyde allows, under physiological conditions, to bind a wide variety of biocompatible amines in the structure of the sulfated polysaccharides. The proposed method allows to prepare materials suitable for pH-responsive drug delivery systems, or for the preparation of scaffolds in tissue engineering or regenerative medicine. Formulae for the abstract (I), (II) above, where R is OH, O—SO 2 —OH, O—SO 2 —ONa, or NH—Ac.

Unsaturated Derivatives of Polysaccharides, Method of Preparation Thereof and Use Thereof

The invention relates to the preparation of new polysaccharide derivatives comprising a double bond in the positions 4 and 5 of the pyranose cycle. The method of preparation consists in the oxidation of OH group in the position 6 to an aldehyde, followed by the elimination to form a double —C═C— bond in the positions 4 and 5, and the fmal reduction of the aldehyde group in the position 6 into the original alcohol. The derivatives of polysaccharides prepared according to the invention show an enhanced antioxidant activity and some of them also a selective negative influence on carcinoma cell viability. (formula) where R represents —NH—CO—CHor —OH. 2. Unsaturated derivatives of polysaccharides according to characterized in that their molecular weight is in the range of 5.10to 5.10g.moland that the polysaccharides are selected from the group consisting of chondroitin sulfate claim 1 , carrageenan claim 1 , dermatan sulfate claim 1 , hyaluronic acid claim 1 , and keratan sulfate.4. The method of preparation according to characterized in that the starting polysaccharide is chondroitin sulfate claim 3 , carrageenan claim 3 , dermatan sulfate claim 3 , hyaluronic acid claim 3 , or keratan sulfate.5. The method of preparation according to characterized in that claim 3 , in the first step claim 3 , the oxidation in the position C-6 proceeds either by means of the R-TEMPO/NaClO system claim 3 , where Ris hydrogen or N-acetyl group claim 3 , in water at the temperature of 0° C. to 10° C. claim 3 , wherein the molar amount of NaClO is within the range of 0.3 to 0.8 eq. and the molar amount of R-TEMPO is within the range of 0.005 to 0.2 eq. claim 3 , with respect to the repeating unit of the polysaccharide claim 3 , or by means of 1 claim 3 ,1 claim 3 ,1-triacetoxy-1 claim 3 ,1-dihydro-1 claim 3 ,2-benziodoxol-3(1H)-one (DMP) in DMSO at the temperature of 10° C. to 50° C. claim 3 , wherein the amount of DMP is within the range of 0.05 to 2 eq. claim 3 , with respect to the ...

Method of Crosslinking of Polysaccharides Using Photoremovable Protecting Groups

The invention discloses a method of preparation of crosslinked materials based on polysaccharides using electromagnetic radiation in an aqueous solution containing a polysaccharide with a bound carbamate photoremovable protecting group (PPG with group —NH—CO—O—) and a polysaccharide containing an aldehyde group —CHO. The crosslinking process itself is carried out by means of a condensation reaction of the photochemically released amino group (—NH) with the aldehyde group (—CHO) forming a bond of imine type (—N═CH—). Both processes proceed simultaneously and they can be performed under physiological conditions. The advantage of the suggested solution is the temporal and spatial control of crosslinking that allows the preparation of advanced materials for tissue engineering where the crosslink density and thus the mechanical properties in the material structure can be tailored. 1. A method of preparation of crosslinked polysaccharide materials according to the general formula (I){'br': None, 'sup': '1', 'polysaccharide1-R—N═CH-polysaccharide2\u2003\u2003(I)'}{'sup': '1', 'sub': 1', '30', '1', '30', '1', '30, 'where polysaccharide1 and polysaccharide2 are identical or different polysaccharides and Ris C-Calkyl residue, C-Calkylaryl residue or C-Calkylheteroaryl residue, optionally containing one or more identical or different heteroatoms selected from the group comprising N, O, S, characterized in that'} {'br': None, 'polysaccharide2-CH═O\u2003\u2003(III),'}, 'an aqueous solution of aldehyde of polysaccharide 2 according to the general formula III'} {'br': None, 'sup': 1', '2, 'sub': '2', 'polysaccharide1-R—NH—CO—O—CH—R\u2003\u2003(II),'}, 'where the substitution degree of aldehyde in polysaccharide2 is within the range of 1 to 50%, is added to an aqueous solution of polysaccharide 1 substituted on the site of amino group by a photoremovable group, according to the general formula II'}{'sup': 1', '2, 'where Ris defined above; Ris an aromatic system, and where the ...

CARBOXYLATED DERIVATIVES OF GLYCOSAMINOGLYCANS AND USE AS DRUGS

A glycosaminoglycan derivative endowed with heparanase inhibitory activity and antitumor activity, bearing carboxylate groups in positions 2 and 3 of at least part of the glycosaminoglycan residues, and to the process for preparing the same. The glycosaminoglycan derivatives of the present invention are generated starting from natural or synthetic glycosaminoglycans, preferably heparin or low molecular weight heparin, optionally 2-O- and 2-N-desulfated by two steps of oxidation. By the first oxidation, adjacent dials and optionally adjacent OH/NHof the glycosaminoglycan residues are converted to aldehydes and by the second oxidation said dialdehydes are converted to carboxylate groups. The first oxidation preferably leads to the cleavage of C2-C3 linkage of the ring of oxidable residues. The invention relates to a process for the preparation of said glycosaminoglycan derivatives and to their use as active ingredients of medicaments. 1. A glycosaminoglycan derivative which is obtainable by{'sub': '2', 'a) oxidation of 10% to 100%, of 2-O; and optionally 2-N-, 3-O-, non-sulfated residues of a glycosaminoglycan, under conditions effective to convert adjacent diols and optionally adjacent OH/NHto dialdehydes;'}b) oxidation of the oxidized glycosaminoglycan under conditions effective to convert said dialdehydes to carboxylate groups;wherein the glycosaminoglycan is selected from heparin, heparan sulfate, optionally 2-O- and/or 2-N-desulfated.2. The glycosaminoglycan derivative of claim 1 , wherein the glycosaminoglycan has a sulfate degree (SO/COO—) determined by conductimetric titration of from 0.8 to 2.8.3. The glycosaminoglycan derivative of claim 2 , wherein the glycosaminoglycan has a sulfation degree (SO/COO—) determined by conductimetric titration of from 0.9 to 2.5.4. The glycosaminoglycan derivative of claim 1 , wherein the glycosaminoglycan derivative has a carboxyl increment of from 1.2 to 2.2.5. The glycosaminoglycan derivative of claim 1 , wherein in step a) ...

GLYCOSAMINOGLYCAN DERIVATIVE AND METHOD FOR PRODUCING SAME

The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance. 1. A method for treating inflammation , the method comprising;administering to a subject an effective amount of a pharmaceutical composition;wherein the pharmaceutical composition comprising a glycosaminoglycan derivative;wherein the glycosaminoglycan derivative comprising a group derived from glycosaminoglycan and a group derived from a physiologically active substance, which are coupled by a covalent bond with a spacer therebetween;wherein the glycosaminoglycan is hyaluronic acid or a pharmaceutically acceptable salt thereof;wherein the physiologically active substance is diclofenac;wherein the group derived from a physiologically active substance and the spacer are covalently bonded through an ester bond;wherein the group derived from glycosaminoglycan and the spacer are covalently bonded through an amide bond;wherein a coupling group contained in a spacer-forming molecule is an aliphatic hydrocarbon with 2 carbon atoms;wherein the coupling group may have one or more substituent selected from the group consisting of a methyl group, an ethyl group, a propyl group, a butyl group, an isopropyl group, an isobutyl group, a tert-butyl group, a cyclohexyl group, and a phenyl group;wherein a molecular weight degradation rate of the glycosaminoglycan derivative after storing the pharmaceutical composition at 60° C. for 1 week is not more than 25%; andwherein a dissociation ratio of the diclofenac from the glycosaminoglycan derivative after storing the pharmaceutical composition at 60° C. for 1 week is not more than 20%.2. The method ...

CROSS-LINKED POLYMER MATRICES, AND METHODS OF MAKING AND USING SAME

Functionalized chondroitin sulfate, cross-linked polymer matrices comprising functionalized chondroitin sulfate, and methods of making and using the same are provided. Such polymer matrices may be used for tissue engineering, reconstructing cartilage, and the like. Kits are also provided for detection of cartilage degrading enzymes. 1. A composition comprising at least one monomeric unit of chondroitin sulfate functionalized by at least one polymerizable moiety.2. The composition according to claim 1 , wherein said composition comprises at least ten monomeric units of chondroitin sulfate.3. (canceled)4. The composition according to claim 2 , wherein said polymerizable moiety is selected from the group consisting of methacrylates claim 2 , ethacrylates claim 2 , itaconates claim 2 , acrylamides claim 2 , and aldehydes.5. The composition according to claim 4 , wherein said polymerizable moiety is methacrylate.6. (canceled)9. The composition of claim 1 , further comprising at least one monomeric unit of a biocompatible polymer.10. The composition of claim 9 , wherein said biocompatible polymer is polyethylene glycol.11. (canceled)12. A composition comprising a cross linked polymer matrix claim 9 , wherein said cross-linked polymer matrix comprises at least one monomeric unit of functionalized chondroitin sulfate.13. The composition of claim 12 , wherein said monomeric unit of chondroitin sulfate is functionalized with an alkenyl moiety.14. The composition of claim 12 , wherein said monomeric unit of chondroitin sulfate is functionalized with an aldehyde moiety.15. The composition of claim 13 , wherein said alkenyl moiety is methacrylate.1622.-. (canceled)23. The composition of claim 12 , wherein said cross-linked polymer matrix further comprises at least one monomeric unit of a biocompatible polymer.2426.-. (canceled)27. The composition of claim 23 , wherein said biocompatible polymer is poly(ethylene glycol).2837.-. (canceled)38. A method of producing a composition ...

CARBOXYLATED DERIVATIVES OF GLYCOSAMINOGLYCANS AND USE AS DRUGS

A glycosaminoglycan derivative endowed with heparanase inhibitory activity and antitumor activity, bearing carboxylate groups in positions 2 and 3 of at least part of the glycosaminoglycan residues, and to the process for preparing the same. The glycosaminoglycan derivatives of the present invention are generated starting from natural or synthetic glycosaminoglycans, preferably heparin or low molecular weight heparin, optionally 2-O- and 2-N-desulfated by two steps of oxidation. By the first oxidation, adjacent dials and optionally adjacent OH/NHof the glycosaminoglycan residues are converted to aldehydes and by the second oxidation said dialdehydes are converted to carboxylate groups. The first oxidation preferably leads to the cleavage of C2-C3 linkage of the ring of oxidable residues. The invention relates to a process for the preparation of said glycosaminoglycan derivatives and to their use as active ingredients of medicaments. 3. The carboxylated derivative of a glycosaminoglycan according to claim 1 , wherein the glycosaminoglycan that the carboxylated derivative is derived from is selected from one of unfractionated heparin claim 1 , low molecular weight heparin claim 1 , and heparan sulfate.4. The carboxylated derivative of a glycosaminoglycan according to claim 3 , wherein the unfractionated heparin is 2-O-desulfated unfractionated heparin claim 3 , 2-N-desulfated unfractionated heparin or 2-O- claim 3 , 2-N-desulfated unfractionated heparin.5. The carboxylated derivative of a glycosaminoglycan according to claim 3 , wherein the low molecular weight heparin is 2-O-desulfated low molecular weight heparin claim 3 , 2-N-desulfated low molecular weight heparin or 2-O- claim 3 , 2-N-desulfated low molecular weight heparin.6. The carboxylated derivative of a glycosaminoglycan according to claim 1 , wherein the glycosaminoglycan that the carboxylated derivative is derived from has a sulfation degree (SO/COO) claim 1 , determined by conductimetric titration as ...

Preparation and/or Formulation of Proteins Cross-Linked with Polysaccharides

Therapeutic compositions and/or formulations are provided, comprising: at least one cross-linked protein matrix, wherein the at least one cross-linked protein matrix comprises at least one protein residue and at least one saccharide-containing residue, and methods of producing the same. The cross-linked protein matrix may be derived from cross-linking a full length or substantially full length protein, such as tropoelastin, elastin, albumin, collagen, collagen monomers, immunoglobulins, insulin, and/or derivatives or combinations thereof, with a saccharide containing cross-linking agent, such as a polysaccharide cross-linking agent derived from, for example, hyaluronic acid or a cellulose derivative. The therapeutic compositions may be administered topically or by injection. The present disclosure also provides methods, systems, and/or kits for the preparation and/or formulation of the compositions disclosed herein.

COMPOSITIONS AND METHODS FOR BACTERIAL PRODUCTION OF CHONDROITIN

The invention relates to the field of recombinant DNA technology for the production of chondroitin, including the production of chondroitin sulfate via a combination of recombinant bacterial fermentation and post-fermentation sulfation. 164-. (canceled)65. A construct comprising a kfoA , kfoC , and kfoF gene , wherein the construct does not contain a functional gene of one or more of kfoD , orf3(kfoI) , kfoE , or orf1(kfoH) , and wherein the construct is suitable for producing chondroitin in a non-pathogenic bacterial host cell.66. The construct of claim 65 , wherein the construct further comprises a kfoG gene claim 65 , a kfoB gene claim 65 , or a combination thereof.67. The construct of claim 65 , wherein the chondroitin is non-fructosylated.68. The construct of claim 65 , wherein the construct further comprises a kpsF claim 65 , kpsE claim 65 , kpsD claim 65 , kpsU claim 65 , kpsC claim 65 , and kpsS gene.69. The construct of claim 68 , wherein the construct further comprises a kpsM and kpsT gene.70. The construct of claim 68 , wherein the chondroitin is secreted from the host cell.71. The construct of claim 65 , wherein the construct also does not contain a functional gene of one or more of kpsM claim 65 , kpsT claim 65 , kpsE claim 65 , kpsD claim 65 , kpsC claim 65 , or kpsS.72. The construct of claim 71 , wherein the chondroitin is not secreted from the host cell.73. The construct of claim 65 , wherein one or more genes are modified for optimal codon usage in a bacterial host cell.74. The construct of claim 65 , comprising a K4 gene cluster.75. A non-pathogenic bacterial host cell comprising the construct of .76Escherichia, Pseudomonas, Xanthomonas, Methylomonas, AcinetobacterSphingomonas.. The non-pathogenic bacterial host cell of claim 75 , wherein the non-pathogenic bacterial host cell is or is derived from a non-pathogenic organism selected from the group consisting of claim 75 , and77. The non-pathogenic bacterial host cell of claim 76 , wherein the ...

HYALURONIC ACID-BINDING SYNTHETIC PEPTIDOGLYCANS, PREPARATION, AND METHODS OF USE

This invention pertains to the field of hyaluronic acid-binding synthetic peptidoglycans and methods of forming and using the same. 1. A synthetic peptidoglycan comprising a glycan and 1 to 20 synthetic peptides conjugated to the glycan , wherein each synthetic peptide is 5 to 40 amino acids in length and comprises a hyaluronic acid-binding amino acid sequence and wherein the synthetic peptidoglycan in the peptidoglycan can bind to a hyaluronic acid.2. The synthetic peptidoglycan of wherein each synthetic peptide comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 claim 1 ,wherein X8 is present or is not present,wherein B1 is a basic amino acid,wherein B2 is a basic amino acid, andwherein X1-X8 are non-acidic amino acids.4. The synthetic peptidoglycan of claim 1 , wherein the glycan is selected from the group consisting of dextran claim 1 , chondroitin claim 1 , chondroitin sulfate claim 1 , dermatan claim 1 , dermatan sulfate claim 1 , heparan claim 1 , heparin claim 1 , keratin claim 1 , and keratan sulfate.513.-. (canceled)14. A method of treatment for arthritis in a patient claim 1 , said method comprising administering to the patient an effective amount of the synthetic peptidoglycan of .15. The method of wherein each synthetic peptide comprises an amino acid sequence of the formula B1-X1-X2-X3-X4-X5-X6-X7-X8-B2 claim 14 ,wherein X8 is present or is not present,wherein B1 is a basic amino acid,wherein B2 is a basic amino acid, andwherein X1-X8 are non-acidic amino acids.17. The method of wherein the glycan is selected from the group consisting of dextran claim 14 , chondroitin claim 14 , chondroitin sulfate claim 14 , dermatan claim 14 , dermatan sulfate claim 14 , heparan claim 14 , heparin claim 14 , keratin claim 14 , and keratan sulfate.18. The method of wherein the synthetic peptidoglycan is resistant to aggrecanase.19. The method of wherein each synthetic peptide has a glycine-cysteine attached to the C-terminus of the peptide.20 ...

BIOTECHNOLOGICAL SULPHATED CHONDROITIN SULPHATE AT POSITION 4 OR 6 ON THE SAME POLYSACCHARIDE CHAIN, AND PROCESS FOR THE PREPARATION THEREOF

The present invention discloses a process for the production of chondroitin sulphate with an average molecular weight (Mw) of 10-30 kDa by chemical sulphation starting from an unsulphated chondroitin backbone, obtained in turn by acid hydrolysis of capsular polysaccharide K4 made directly from strain O5:K4:H4, or directly produced from a genetically modified strain of . Sulphation of the N-acetyl-D-galactosamine residue at position 4 or 6 takes place simultaneously in the same polysaccharide chain, simulating the sulphation pattern observed in natural chondroitin sulphate, unlike the sulphation obtained with the synthesis methods described to date. 2E. ColiE. Coli. The process of wherein the chondroitin sodium salt of step a) is obtained starting either from the capsular polysaccharide K4 produced by a culture broth of strain O5:K4:H4 claim 1 , or from the polysaccharide produced by a culture broth of strain DSM23644.3. The process of wherein step b) is carried out with an orthoester selected from trimethyl orthoacetate claim 1 , triethyl orthoacetate claim 1 , trimethyl orthoformate claim 1 , triethyl orthoformate claim 1 , trimethyl orthopropionate claim 1 , triethyl orthopropionate or trimethyl orthobenzoate.4. The process of wherein the acid catalysis of step b) is carried out with an acid selected from camphorsulphonic acid claim 1 , para-toluenesulphonic acid claim 1 , methanesulphonic acid or with a sulphone resin.5. The process of wherein step c) is effected with acetic anhydride.6. The process of wherein step d) is effected at 20 to 40° C. claim 1 , preferably at room temperature.7. The process of wherein step d) is effected at 40 to 70° C. claim 1 , preferably at 60° C.8. The process of wherein step d) is effected in a water/organic water-soluble acid mixture or in water alone.9. The process of claim 8 , wherein the organic acid is selected from acetic claim 8 , formic claim 8 , propionic claim 8 , tartaric claim 8 , citric acid or a propionic resin.10. ...

CROSS-LINKED POLYMER MATRICES, AND METHODS OF MAKING AND USING SAME

Functionalized chondroitin sulfate, cross-linked polymer matrices comprising functionalized chondroitin sulfate, and methods of making and using the same are provided. Such polymer matrices may be used for tissue engineering, reconstructing cartilage, and the like. Kits are also provided for detection of cartilage degrading enzymes. 1. A composition comprising at least one monomeric unit of chondroitin sulfate functionalized by at least one polymerizable moiety.2. The composition according to claim 1 , wherein said composition comprises at least ten monomeric units of chondroitin sulfate.3. (canceled)4. The composition according to claim 2 , wherein said polymerizable moiety is selected from the group consisting of methacrylates claim 2 , ethacrylates claim 2 , itaconates claim 2 , acrylamides claim 2 , and aldehydes.5. The composition according to claim 4 , wherein said polymerizable moiety is methacrylate.6. (canceled)9. The composition of claim 1 , further comprising at least one monomeric unit of a biocompatible polymer.10. The composition of claim 9 , wherein said biocompatible polymer is polyethylene glycol.11. (canceled)12. A composition comprising a cross linked polymer matrix claim 9 , wherein said cross-linked polymer matrix comprises at least one monomeric unit of functionalized chondroitin sulfate.13. The composition of claim 12 , wherein said monomeric unit of chondroitin sulfate is functionalized with an alkenyl moiety.14. The composition of claim 12 , wherein said monomeric unit of chondroitin sulfate is functionalized with an aldehyde moiety.15. The composition of claim 13 , wherein said alkenyl moiety is methacrylate.1622.-. (canceled)23. The composition of claim 12 , wherein said cross-linked polymer matrix further comprises at least one monomeric unit of a biocompatible polymer.2426.-. (canceled)27. The composition of claim 23 , wherein said biocompatible polymer is poly(ethylene glycol).2837.-. (canceled)38. A method of producing a composition ...

DERIVATIVES OF N-DESULFATED GLYCOSAMINOGLYCANS AND USE AS DRUGS

A glycosaminoglycan derivative which is obtainable by a process that includes the steps of N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan, and oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NHto aldehydes. The process further includes reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols, where the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof. 1. A glycosaminoglycan derivative which is obtainable by the following process:a) N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan;{'sub': '2', 'b) oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NHto aldehydes;'} 'wherein the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof.', 'c) reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols;'}2. The glycosaminoglycan derivative of claim 1 , wherein the process further comprising:d) 2-O-desulfation of up to 50% of the 2-O-sulfated residues of the glycosaminoglycan, before or after N-desulfation.3. The glycosaminoglycan derivative of claim 2 , wherein said d) 2-O-desulfation of up to 25% of the 2-O-sulfated residues of the glycosaminoglycan.4. The glycosaminoglycan derivative of claim 1 , wherein the process further comprising:e) partial or total deacetylation of the N-acetylated residues of the glycosaminoglycan, before ...

LOW POLYDISPERSITY, LOW MOLECULAR WEIGHT BIOTECHNOLOGICAL CHONDROITIN SULFATE WITH ANTI-INFLAMMATORY AND ANTIARTHRITIS ACTIVITY AND USE THEREOF IN THE PREVENTION OF OSTEOARTHRITIS

Disclosed is a low molecular weight (1000-5000 daltons) chondroitin sulfate (CS) produced by chemical sulfation of a non-sulfated chondroitin backbone (K4 capsular polysaccharide) obtained with biotechnology techniques. The CS described is substantially monosulfated, mainly at the 6-position, with very little sulfation at the 4-position, and with a mono/disulfated disaccharide ratio and charge density similar to those of natural CS. Said biotechnological chondroitin sulfate (CS) is useful in the treatment and prevention of osteoarthritis and in acute and chronic inflammatory processes. 1. A biotechnological chondroitin sulfate comprising:6-monosulfate disaccharides in an amount equal to or greater than 65% by weight;4-monosulfate disaccharides in an amount less than about 1% by weight;2,6-disulfate disaccharides in an amount less than or equal to 20% by weight;4,6-disulfate disaccharides in an amount less than about 5% by weight;2,4-disulfate disaccharides in an amount less than about 1% by weight;trisulfated disaccharides in an amount less than about 1% by weight;non-sulfated disaccharides in an amount less than about 15% by weight;a charge density value ranging from about 1 to about 1.25; anda polydispersity index ranging from about 1.1 to about 1.3.2. The chondroitin sulfate of claim 1 , wherein the molecular weight (Mw) of the chondroitin sulfate ranges from 1000 to 5000 daltons.3. The chondroitin sulfate of claim 1 , wherein the chondroitin sulfate is obtained by chemical sulfation of the low-molecular-weight chondroitin or capsular polysaccharide K4-d obtained from fermentation.4E. coli. The chondroitin sulfate of claim 3 , wherein the chondroitin is obtained by removal of the fructose residues of polysaccharide K4 of by means of hydrolysis.5. The chondroitin sulfate of claim 3 , wherein the low-molecular-weight chondroitin is obtained by acid or radical depolymerization of the polysaccharide K4.6. The chondroitin sulfate of claim 3 , wherein the low-molecular ...

Biocompatible Hydrogel Compositions

The present disclosure encompasses biocompatible hydrogel compositions comprising covalently bonded hydrogel reaction products, as well as compositions of, methods of producing, methods of using, and kits comprising the covalently cross-linked hydrogel reaction products. The covalently cross-linked hydrogel reaction products can be derived from a cross-linking reaction of a polyquaternium-10, a chondroitin 4-sulfate, and a divinylsulfone.

METHOD OF PURIFYING LOW MOLECULAR WEIGHT HYALURONIC ACID OR CATIONIZED HYALURONIC ACID VIA PRECIPITATION FROM AQUEOUS SOLUTION BY ADDITION OF ALCOHOL OR ACETONE FOLLOWED BY pH ADJUSTMENT

Provided a method of producing a purified hyaluronic acid type which comprises adding a water-soluble organic medium to a solution which comprises a hyaluronic acid type having an average molecular weight of 400 to 100,000 and has a pH of 3 or less to obtain a suspension, and adjusting a pH of the suspension in a range of 3.5 to 8 to precipitate a purified hyaluronic acid type.

CROSSLINKED POLYMERIC NETWORK AND USE THEREOF

A crosslinked polymeric network is disclosed. The crosslinked polymeric network comprises a reaction product of a first glycosaminoglycan, a second glycosaminoglycan, and a crosslinking agent, wherein the first glycosaminoglycan is different than the second glycosaminoglycan. 1. A crosslinked polymeric network comprising a reaction product of a first glycosaminoglycan , a second glycosaminoglycan , and a first crosslinking agent , wherein the first glycosaminoglycan is different than the second glycosaminoglycan.2. The crosslinked polymeric network of claim 1 , wherein the first glycosaminoglycan and the second glycosaminoglycan are independently selected from the group consisting of chondroitin claim 1 , chondroitin sulfate claim 1 , dermatan claim 1 , dermatan sulfate claim 1 , heparin claim 1 , heparan sulfate claim 1 , hyaluronan claim 1 , hyaluronic acid claim 1 , sucrose claim 1 , lactulose claim 1 , lactose claim 1 , maltose claim 1 , trehalose claim 1 , cellobiose claim 1 , mannobiose and chitobiose.3. The crosslinked polymeric network of claim 1 , wherein the first glycosaminoglycan is hyaluronic acid and the second glycosaminoglycan is chondroitin sulfate.5. The crosslinked polymeric network of claim 4 , wherein GAG is hyaluronic acid and GAG′ is chondroitin sulfate.7. The crosslinked polymeric network of claim 6 , wherein GAG is hyaluronic acid and GAG′ is chondroitin sulfate.9. The crosslinked polymeric network of claim 8 , wherein GAG is hyaluronic acid and GAG′ is chondroitin sulfate.11. The crosslinked polymeric network of claim 10 , wherein GAG is hyaluronic acid and GAG′ is chondroitin sulfate.12. The crosslinked polymeric network of claim 1 , wherein the first crosslinking agent is a bi- or polyfunctional crosslinking agent comprising two or more functional groups capable of reacting with functional groups of the first glycosaminoglycan and the second glycosaminoglycan.13. The crosslinked polymeric network of claim 1 , wherein the first ...

Mercapto-modified biocompatible macromolecule derivatives with low degree of mercapto-modification and the cross-linked materials and uses thereof

The present invention discloses a mercapto-modified biocompatible macromolecule derivative with a low degree of modification. The mercapto-modified biocompatible macromolecule derivative not only maintains the initial structure, physiological function and biocompatibility as much as possible, but also allows the preparation of the biocompatible macromolecule cross-linked material with a low degree of cross-linking through the effectively chemical cross-linking with the introduced mercapto group. The present invention further discloses a disulfide-bond cross-linked biocompatible macromolecule material with a very low degree of cross-linking. The disulfide-bond cross-linked biocompatible macromolecule material not only maintains the initial structure, physiological function and biocompatibility of the biocompatible macromolecule as much as possible, but also effectively prolongs turn over and reduces the solubility of the biocompatible macromolecule in vivo, better meeting the requirements of various clinical applications. The present invention further relates to the application of the disulfide-bond cross-linked biocompatible macromolecule material in the field of medicine and pharmacy.

PREPARATION AND/OR FORMULATION OF PROTEINS CROSS-LINKED WITH POLYSACCHARIDES

Therapeutic compositions and/or formulations are provided, comprising: at least one cross-linked protein matrix, wherein the at least one cross-linked protein matrix comprises at least one protein residue and at least one saccharide-containing residue, and methods of producing the same. The cross-linked protein matrix may be derived from cross-linking a full length or substantially full length protein, such as tropoelastin, elastin, albumin, collagen, collagen monomers, immunoglobulins, insulin, and/or derivatives or combinations thereof, with a saccharide containing cross-linking agent, such as a polysaccharide cross-linking agent derived from, for example, hyaluronic acid or a cellulose derivative. The therapeutic compositions may be administered topically or by injection. The present disclosure also provides methods, systems, and/or kits for the preparation and/or formulation of the compositions disclosed herein. 1. A kit comprising:(a) a prefilled syringe, wherein the prefilled syringe is filled with a tissue compatible composition comprising a protein selected from the group consisting of tropoelastin and albumin; a hyaluronic acid cross-linking molecule comprising one or more carboxyl groups; and at least one intermolecular cross-linkage comprising an amide bond between an amine of the protein and a carboxyl group of the hyaluronic acid cross-linking molecule; and(b) instructions for use.2. The kit of claim 1 , further comprising an assortment of appropriate sized needles.3. The kit of claim 2 , wherein the assortment of appropriately sized needles comprise fine gauge needles.4. The kit of claim 3 , wherein the needles range from about 25 gauge to about 31 gauge.5. The kit of claim 2 , wherein the needles range from about 18 gauge to about 31 gauge.6. The kit of claim 1 , further comprising a needle delivery system.7. The kit of claim 6 , wherein the needle delivery system is selected from a needle roller ball type system claim 6 , an automatic injection pen ...

ENZYMATIC SYNTHESIS OF HOMOGENEOUS CHONDROITIN SULFATE OLIGOSACCHARIDES

Methods of synthesizing chondroitin sulfate oligosaccharides are provided. Enzymatic schematic approaches to synthesizing structurally defined homogenous chondroitin sulfate oligosaccharides at high yields are provided. Synthetic chondroitin sulfate oligosaccharides ranging from 3-mers to 15-mers are provided. 1. A method of synthesizing a synthetic chondroitin sulfate oligosaccharide , the method comprising:providing a chondroitin backbone; andperforming at least two of the following enzymatic reaction steps:{'i': 'E. coli', 'an elongation step to add a GalNAc residue using a glycosyltransferase from K4 (KfoC);'}an elongation step to add a GlcA residue using KfoC;a 6-O-sulfation step using chondroitin sulfate 6-O-sulfotransferase (CS6OST) and sulfate donor 3′-phosphoadenosine 5′-phosphosulfate (PAPS); anda 4-O-sulfation step involving chondroitin sulfate 4-O-sulfotransferase (CS4OST) and PAPS;whereby a synthetic chondroitin sulfate oligosaccharide is synthesized.2. The method of claim 1 , further comprising a step of transferring a GalNTFA residue to a trisaccharide backbone by a KfoC to yield a tetrasaccharide.3. The method of claim 1 , wherein at least three of the enzymatic reaction steps are performed.4. The method of claim 1 , wherein at least four of the enzymatic reaction steps are performed.5. The method of claim 1 , wherein the method yields substantially homogenous chondroitin sulfate oligosaccharides.6. The method of claim 1 , wherein the method yields 4-O-sulfated and/or 6-O-sulfated chondroitin oligosaccharides having a size ranging from a trisaccharide to a nonasaccharide.7. The method of claim 1 , wherein the method yields a chondroitin sulfate ranging in size from a 3-mer to a 15-mer.8. The method of claim 1 , wherein the method yields an unnatural chondroitin sulfate oligosaccharide.9. The method of claim 1 , wherein the method yields a structurally defined chondroitin sulfate oligosaccharide.10. The method of claim 1 , wherein the method yields at ...

DERIVATIVES OF N-DESULFATED GLYCOSAMINOGLYCANS AND USE AS DRUGS

A glycosaminoglycan derivative which is obtainable by a process that includes the steps of N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan, and oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NHto aldehydes. The process further includes reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols, where the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof. 1. A glycosaminoglycan derivative which is obtainable by the following process:a) N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan;{'sub': '2', 'b) oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NHto aldehydes;'}c) reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols;wherein the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof.2. The glycosaminoglycan derivative of claim 1 , wherein the process further comprising:d) 2-O-desulfation of up to 50% of the 2-O-sulfated residues of the glycosaminoglycan, before or after N-desulfation.3. The glycosaminoglycan derivative of claim 2 , wherein said d) 2-O-desulfation of up to 25% of the 2-O-sulfated residues of the glycosaminoglycan.4. The glycosaminoglycan derivative of claim 1 , wherein the process further comprising:e) partial or total deacetylation of the N-acetylated residues of the glycosaminoglycan, before or ...

Compositions and Methods For Treating Joints

Compositions and methods are disclosed for the treatment of osteoarthritis. The compositions comprising combinations of hyaluronic acid, glucosamine, and chondroitin sulfate, can be useful for any synovial joint, including the knee, shoulder, hip, ankle, hands, spinal facet, or temporomandibular joint, both for the relief of pain and for slowing disease progression.

SOLID STATE NANOPORES AIDED BY MACHINE LEARNING FOR IDENTIFICATION AND QUANTIFICATION OF HEPARINS AND GLYCOSAMINOGLYCANS

The present disclosure provides a method for identifying and quantifying sulfated glycosaminoglycans, including for example heparin, by passing a sample through nanopores. The glycosaminoglycans sample is measured in microliter quantities, at nanomolar concentrations with detection of impurities below 0.5%, and a dynamic range over five decades of magnitude with a trained machine learning algorithm. 1. A method for characterizing the purity of glycosaminoglycans , comprising:(a) passing one or more calibration samples through a first silicon nitride nanopore while recording a translocation current signal;(b) passing a negatively charged glycosaminoglycan sample to be characterized through the first silicon nitride nanopore or a second silicon nitride nanopore while recording a translocation current signal; and(c) using a machine learning algorithm to determine the purity of the negatively charged glycosaminoglycan sample to be characterized from the translocation current signals.2. The method of where the first and second silicon nitride nanopores are fabricated in a solid state membrane.3. The method of in which the machine learning algorithm is a Support Vector Machine.4. The method of wherein the Support Vector Machine is trained with data from the one or more calibration samples.5. The method of wherein the negatively charged glycosaminoglycan sample is prepared from a blood sample.6. The method of wherein the blood sample is a human blood sample.7. The method of wherein the negatively charged glycosaminoglycan sample comprises heparin.8. The method of wherein the negatively charged glycosaminoglycan sample comprises chondroitin sulfate.9. The method of wherein the negatively charged glycosaminoglycan sample comprises enoxaparin.10. The method of wherein the silicon nitride nanopores are fabricated by drilling with a transmission electron microscope (TEM).11. The method of wherein the silicon nitride nanopores are about 3 nanometers in diameter.12. The method of ...

LOW MOLECULAR WEIGHT CHONDROITIN SULFATE, COMPOSITION, PREPARATION METHOD AND USE THEREOF

The invention relates to a low molecular weight sulfate chondroitin and a preparation method thereof. A low molecular weight chondroitin sulfate with the average molecular weight of less than 1000 Dalton can be obtained by a production process of chondroitin sulfate lyase degradation, deproteinization, filtration and sterilization and drying using macromolecular sulfate chondroitin as a raw material. The low molecular weight Chondroitin sulfate has a narrow molecular weight distribution range, the ratio of chondroitin sulfate disaccharide is 43˜60% and the ratio of chondroitin sulfate tetrasaccharide is 30˜45%, the sum of chondroitin sulfate disaccharide and chondroitin sulfate tetrasaccharide is more than 87%, the total oligosaccharide content of low molecular weight chondroitin sulfate is more than 97% and the protein content is less than 0.5%; Compared with the general market macromolecule chondroitin sulfate, the product has more remarkable repair effect at the concentration of 50˜100 μg/mL on chondrocytes damaged by 1 mM hydrogen peroxide, with strong repair ability and repair rate of 14%˜23%. The low molecular weight chondroitin sulfate can be used to treat joint injury and is an important raw material for medical products, health care products, cosmetics and food.

PROCESS FOR ISOLATING BIOACTIVE BIOMOLECULES FROM ANIMAL BY-PRODUCTS

A process for producing a plurality of biomolecule products from by-products of animal food processing is described. The process includes the steps of mixing the by-products with one or more digestive enzymes in the presence of an acid to promote hydrolysis of the by-product to release the biomolecules, thereby providing a hydrolysis mixture. The hydrolysis mixture is subjected to a density-based fractional separation, thereby providing an oil fraction, a liquid fraction and a solid fraction. Then the liquid fraction is separated from the oil and solid fractions and filtered with a molecular mass cutoff filter, thereby providing a peptide product and a glycosaminoglycan product. The oil fraction may be further refined to provide an oil product and the solid fraction may be further processed to provide bone-derived products such as gelatin, ossein and collagen. 1. A process for producing a plurality of biomolecule products from by-products of animal food processing , the process comprising:mixing the by-products with one or more digestive enzymes in the presence of an acid to promote hydrolysis of the by-product to release the biomolecules, thereby providing a hydrolysis mixture;subjecting the hydrolysis mixture to a density-based fractional separation, thereby providing an oil fraction, a liquid fraction and a solid fraction; andseparating the liquid fraction from the oil and solid fractions and filtering the liquid fraction with a molecular mass cutoff filter, thereby providing a peptide product and a glycosaminoglycan product.2. The process of claim 1 , further comprising processing bone tissue contained in the solid fraction to generate one or more of or a combination of: a collagen product claim 1 , a gelatin product and an ossein product.3. The process of claim 1 , further comprising processing the oil to provide a refined oil product.4. The process of claim 1 , wherein the step of mixing the by-products further includes homogenization of the by-products.5. The ...

Photo-coupled synergistically crosslinked hydrogel material and its composition, preparation method, use, product, and preparation kit

This invention provides a preparation, composition, product, and application of a photo-coupled synergistically crosslinked hydrogel material. The preparation includes dissolving Component A including a photosensitive polymer derivative having o-nitrobenzyl phototriggers and Component B including a polymer derivative having amine or alkene (double group) or sulfhydryl group in a biocompatible medium to obtain solution A and solution B, respectively; mixing the solution A and solution B homogeneously to obtain a hydrogel precursor solution; initiating photo-coupled synergistic crosslinking under an irradiation of a UV light to form the hydrogel. The irradiation causes the o-nitrobenzyl phototriggers to generate an aldehyde group/keto group or a nitroso group to initiate photo-coupled synergetic crosslinking. The photo-coupled synergistically crosslinked hydrogel has applications in tissue engineering, regenerative medicine, 3D printing and as a carrier of cell, protein or drug.

Hydrogen sulfide releasing polymer compounds

The invention provides a hydrogen sulfide releasing polymer compound having a polysaccharide backbone, wherein the compound has at least two substructures, and wherein said substructures are capable of releasing hydrogen sulfide by thiol activation as well as uses thereof. Additionally, a method of treatment and prevention of a skin condition, an ocular disease or osteoarthritis is provided.

Selectin and icam/vcam peptide ligand conjugates

The invention relates to peptide conjugates that can bind to endothelial cells, and that are useful for reducing the incidence and severity of endothelial dysfunction in mammals.

CONJUGATE OF A FRAGMENT OF A CELLULAR WALL OF A BACTERIUM AND A MUCOPOLYSACCHARIDIC CARRIER, AND USES IN MEDICINE THEREOF

The present invention relates in one aspect to a conjugate of a mucopolysaccharide or mucopolysaccharidic fraction and a cellular wall fragment of a bacterium belonging to the genus, and in particular to the species, also named P40. The conjugate of the invention is applied to medicine, in particular for topical treatment of infections, dermatological affections, such as psoriasis, acne, allergic reactions, such as rashes and eczema, and in vaginal mucosae affections. 1Corynebacterium granulosum. A conjugate of a fragment of a cellular wall of P40 and a physiologically acceptable carrier , wherein the physiologically acceptable carrier comprises a mucopolysaccharide or a mucopolysaccharidic fraction.2. Conjugate according to claim 1 , wherein the physiologically acceptable mucopolysaccharide or mucopolysaccharidic fraction is selected from hyaluronic acid claim 1 , chondroitin-4-sulfate claim 1 , chondroitin-6-sulfate claim 1 , dermatan sulfate claim 1 , heparan sulfate claim 1 , heparin claim 1 , keratan-sulfate and mixtures thereof.3Corynebacterium granulosumCorynebacterium granulosum.. The conjugate according to claim 1 , wherein the fragment of a cellular wall of P40 is an insoluble fraction isolated from a delipidated cellular wall of4. A medical device or medicine comprising the conjugate according to .5. A method for modulating the immune or antibody response of skin and/or mucosa comprising: applying on the skin or mucosa an effective amount of the conjugate according to .6. A method for the prevention or treatment of dermatological bacterial claim 1 , viral or fungal infections comprising: administering an effective amount of the conjugate according to .7. A method for the topical treatment of dermatological affections or disorders comprising: applying on skin an effective amount of the conjugate according to .8. A method for the prevention or treatment of allergic skin disorders or affections comprising: applying on the skin an effective amount of the ...

HYALURONIC ACID-BINDING SYNTHETIC PEPTIDOGLYCANS, PREPARATION, AND METHODS OF USE

This invention pertains to the field of hyaluronic acid-binding synthetic peptidoglycans and methods of forming and using the same.

Chondroitin sulfate derivative and agent for treating bladder diseases

Provided is a compound in which a group derived from chondroitin sulfate and a group derived from a steroid are covalently bonded together via a spacer represented by general formula (I). In the formula, m represents an integer of 0 or 1. Here, if m=0, R 1 represents a group selected from the group consisting of electron-donating groups and steric hindrance groups. If m=1, R 1 represents a group selected from the group consisting of a hydrogen atom, electron-donating groups and steric hindrance groups. —HN—(CH 2 ) m —CHR 1 —CO—  (I)

DIAMINE CROSSLINKING AGENTS, CROSSLINKED ACIDIC POLYSACCHARIDES AND MEDICAL MATERIALS

The invention provides a diamine crosslinking agent for acidic polysaccharides consisting of a diamine compound having a primary amino group at both terminals and an ester or thioester bond in the molecule, wherein the number of atom in the linear chain between at least one of the amino groups and the carbonyl carbon in the ester or thioester is 1 to 5; in particular, a diamine crosslinking agent for acidic polysaccharides which is represented by the general formula (I) below: 2. The crosslinked acidic polysaccharide according to claim 1 , wherein Z is an oxygen atom.3. The crosslinked acidic polysaccharide according to claim 2 , wherein the number of atoms in the linear chain between the amino groups at both terminals is 5 to 8.4. The crosslinked acidic polysaccharide according to claim 2 , wherein the number of atoms in the linear chain between the amino groups at both terminals is 5 or 6.5. The crosslinked acidic polysaccharide according to claim 1 , wherein{'sup': '1', 'Ris a hydrogen atom, or a substituted or unsubstituted alkyl group;'}{'sup': 2', '3', '4', '5, 'Ris a hydrogen atom, a —CONRRgroup or a —COORgroup;'}X is a single bond or an alkanediyl group which is optionally substituted by halogen;Y is a substituted or unsubstituted alkanediyl group;{'sup': 1', '5, 'the substituent(s) in Ris selected from the group consisting of a methyl group, a phenyl group, an indolyl group, a —COORgroup and a —S-Me group; and'}{'sup': '5', 'the substituent(s) in Y is selected from the group consisting of a methyl group, a phenyl group and a —COORgroin.'}6. The crosslinked acidic polysaccharide according to claim 1 , wherein{'sup': 7', '8, 'X is a single bond; Y is a >CRRgroup; and'}{'sup': 7', '8', '3', '4', '5, 'sub': 2', 'n', '2', 'n', '2', '2', 'n', '2', 'n, 'Rand Rare each independently a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 6 carbon atom, a phenyl group, a 4-hydroxyphenyl group, an indolyl group, a diazolyl group, a —(CH)—NHMe group, a —(CH)— ...

Photoactive grafted polysaccharide and use thereof in cosmetics

The invention relates to a polysaccharide polymer of formula (I): PS—(O—CO-L-X) a (OH) b   (I) in which PS denotes the basic backbone of the polysaccharide bearing the hydroxyl groups; L is a divalent hydrocarbon-based group comprising from 1 to 20 carbon atoms; X denotes a photoactive group of azide or diazirine type; a denotes the content of OH groups substituted with the photoactive group; b denotes the content of unsubstituted free OH groups; a being between 0.02 and 0.5; b being between 0.5 and 0.98; and a+b=1. The invention also relates to a composition comprising the polymer (I) in a physiologically acceptable medium, and also to a cosmetic process for caring for the skin, comprising the topical application to the skin of said composition and exposure of the treated skin to light radiation.

MATRICES COMPRISING A MODIFIED POLYSACCHARIDE

The present invention discloses a matrix comprising a modified polysaccharide consisting of repeating disaccharide units whereby in at least 11% of the disaccharide units one primary alcohol group is oxidized into a carboxylic acid group. 119-. (canceled)20. A plastic surgery implant consisting essentially of a matrix comprising:a modified polysaccharide consisting of repeating disaccharide units, whereby in at least 11% of the disaccharide units one primary alcohol group is oxidized to a carboxylic acid group,wherein the matrix further comprises an unmodified polysaccharide component to adjust the mechanical properties of the matrix, and,{'sup': '7', 'wherein the shear modulus G′ of the matrix is in the range of from 10 Pa to 10Pa.'}21. The plastic surgery implant of claim 20 , wherein the modified polysaccharide is selected form the group consisting of a member of the carrageenean family claim 20 , hyaluronic acid claim 20 , heparin sulfate claim 20 , dermatan sulfate claim 20 , chondroitin sulfate claim 20 , alginate claim 20 , chitosan claim 20 , pullulan claim 20 , and agarose.22. The plastic surgery implant of claim 20 , wherein the modified polysaccharide is agarose.23. The plastic surgery implant of claim 20 , wherein the unmodified polysaccharide is selected from the group consisting of a member of the carrageenean family claim 20 , hyaluronic acid claim 20 , heparin sulfate claim 20 , dermatan sulfate claim 20 , chondroitin sulfate claim 20 , alginate claim 20 , chitosan claim 20 , pullulan claim 20 , and agarose.24. The plastic surgery implant of claim 20 , wherein the unmodified polysaccharide is agarose25. The plastic surgery implant of claim 20 , wherein the shear modulus G′ of the matrix is in the range of from 10 Pa to 100 kPa.26. The plastic surgery implant of claim 20 , at least 20-99% of the disaccharide units one primary alcohol group is oxidized to a carboxylic acid group27. The plastic surgery implant of claim 20 , wherein a weight ratio of the ...

CARBOXYL CROSS-LINKED CHONDROITIN HYDROGELS AND THEIR USE FOR SOFT TISSUE APPLICATIONS

A hydrogel product is comprising a chondroitin, molecule selected from the group consisting of chondroitin and chondroitin sulfate as the swellable polymer, wherein the chondroitin molecule is cross-linked into a network via its carboxyl groups. The hydrogel product can be prepared by a process comprising the steps of (a) providing chondroitin molecules; (b) activating the carboxyl groups on the chondroitin molecules with a triazine-based coupling reagent to form an activated, cross-linked chondroitin; and (c) cross-linking the activated chondroitin molecules via their carboxyl groups using a cross-linking agent. The hydrogel product is useful for treatment of soft tissue disorders. 1. A process of preparing a hydrogel product comprising a cross-linked network of chondroitin molecules , comprising the steps of:(a) providing chondroitin molecules selected from the group consisting of chondroitin and chondroitin sulfate;(b) activating the carboxyl groups on the chondroitin molecules with a triazine-based coupling reagent to form an activated, cross-linked chondroitin;(c) cross-linking the activated chondroitin molecules to each other via their carboxyl groups using a cross-linking agent.2. A process according to claim 1 , wherein the cross-linking of step (c) provides amide bonds.3. A process according to claim 1 , wherein the triazine-based coupling reagent is selected from 2-chloro-4 claim 1 ,6-disubstituted-1 claim 1 ,3 claim 1 ,5-triazines in the presence of a tertiary amine base or the corresponding quarternary ammonium salts thereof.4. A process according to claim 3 , wherein the triazine-based coupling reagent is 4-(4 claim 3 ,6-dimethoxy-1 claim 3 ,3 claim 3 ,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM).5. A process according to claim 3 , wherein the triazine-based coupling reagent is 2-chloro-4 claim 3 ,6-dimethoxy-1 claim 3 ,3 claim 3 ,5-triazin (CDMT) together with N-methylmorpholine (NMM).6. A process according to claim 1 , wherein the chondroitin ...

Glycosaminoglycan derivative and method for producing same

The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance.

Bioengineered Regenerative Graft Matrix, and Methods for Making Thereof

A skin-substitute is constructed by homogenizing an acellular dermal tissue matrix into a slurry, pouring the slurry into a mold, and lyophilizing the slurry.

Crosslinked chondroitin sulfate, composition containing same, and treatment agent for eye disease

Provided is a chondroitin sulfate derivative having a cross-linked structure through a group in a polyvalent amine. Also provided is a composition containing the chondroitin sulfate derivative. Also provided are an agent and method for the treatment of an eye disease, the agent and method having a therapeutic effect on a corneal epithelial disorder and/or dry eye.

Polysaccharide derivatives of lipoic acid, their preparation, use as skin cosmetics and medical devices

Disclosed are polysaccharides containing residues of glucosamine or galactosamine in the repetitive unit, characterised by the presence of esters on the hydroxyls or amides on the amine functions, with lipoic acid or with mixtures of lipoic acid and formic acid.

Compositions and Methods for Treating a Disorder or Defect in Soft Tissue

The present invention encompasses methods and compositions for generating a biomimetic proteoglycan. The invention includes methods of treating a disease, disorder, or condition of soft tissue using a biomimetic proteoglycan. 1. A method of generating a biomimetic proteoglycan , said method comprising attaching a glycosaminoglycan (GAG) to a core structure.2. The method of claim 1 , wherein said GAG is selected from the group consisting of hyaluronic acid claim 1 , chondroitin claim 1 , chondroitin sulfate claim 1 , heparin claim 1 , heparin sulfate claim 1 , dermatin claim 1 , dermatin sulfate claim 1 , laminin claim 1 , keratan sulfate claim 1 , chitin claim 1 , chitosan claim 1 , acetyl-glucosamine claim 1 , oligosaccharides claim 1 , and any combination thereof.3. The method of claim 1 , wherein said core structure is selected from the group consisting of a synthetic polymer claim 1 , a protein claim 1 , a peptide claim 1 , a nucleic acid claim 1 , a carbohydrate claim 1 , and any combination thereof.4. The method of claim 1 , wherein said core structure is a synthetic polymer selected from the group consisting poly(4-vinylphenyl boronic acid) claim 1 , poly (3 claim 1 ,3′-diethoxypropyl methacylate) claim 1 , polyacrolein claim 1 , poly(N-isopropyl acrylamide-co-glycidyl methacrylate) claim 1 , poly(allyl glycidyl ether) claim 1 , poly(ethylene glycol) claim 1 , poly(acrylic acid) claim 1 , and any combination thereof.5. The method of claim 1 , wherein said GAG comprises a terminal handle selected from the group consisting of a terminal primary amine claim 1 , terminal diol claim 1 , and an introduced aldehyde.6. The method of claim 1 , wherein said GAG is attached to said core structure by way of a linking chemistry selected from the group consisting of a bornic acid-diol linkage claim 1 , epoxide-amin linkage claim 1 , aldehyde-amine linkage claim 1 , carboxylic acid-amine linkage claim 1 , sulfhydryl-maleimide linkage claim 1 , and any combination thereof.7. ...

Cross-linked polymer matrices, and methods of making and using same

Functionalized chrondroitin sulfate, cross-linked polymer matrices comprising functionalized chrondroitin sulfate, and methods of making and using the same are provided. Such polymer matrices may be used for tissue engineering, reconstructing cartilage, and the like. Kits are also provided for detection of cartilage degrading enzymes.

Crosslinked copolymers based on non-crosslinked polycarboxylic copolymers

The invention concerns crosslinked copolymers based on non-crosslinked polycarboxylic copolymers, said non-crosslinked copolymers containing at least a polysaccharide. The invention also concerns a method for preparing said copolymers and their use in particular as support in pharmaceutical compositions.

Crosslinked copolymers based on non-crosslinked polycarboxylic copolymers

The invention relates to cross-linked copolymers based on non cross-linked polycarboxylic copolymers, said non cross-linked copolymers containing at least one polysaccharide. The invention also relates to a process for the preparation of these copolymers and their use in particular as a support in pharmaceutical compositions.

CROSSLINKED COPOLYMERS BASED ON NON-CROSSLINKED POLYCARBOXYLIC COPOLYMERS

Chondroitin for application in medicine

FIELD: pharmacology. SUBSTANCE: invention is a pharmaceutical composition with anti-inflammatory and antibacterial activity, wound healing, joint repair activity, and antitumour drugs enhancing activity containing an effective amount of non-sulphated chondroitin as an active ingredient. EFFECT: improved activity and effectiveness compared to compositions containing sulfated chondroitin. 19 cl, 19 ex, 18 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 642 964 C2 (51) МПК A61K 31/726 (2006.01) A61K 31/728 (2006.01) A61P 19/02 (2006.01) A61P 27/02 (2006.01) A61P 35/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A61K 31/726 (2006.01); A61K 31/728 (2006.01); A61K 2121/00 (2006.01) (21)(22) Заявка: 2014146519, 22.05.2013 (24) Дата начала отсчета срока действия патента: (73) Патентообладатель(и): АЛЬТЕРГОН С.А. (CH) Дата регистрации: 29.01.2018 23.05.2012 IT MI2012000896 (43) Дата публикации заявки: 10.07.2016 Бюл. № 19 (45) Опубликовано: 29.01.2018 Бюл. № 4 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 23.12.2014 EP 2013/060501 (22.05.2013) C 2 C 2 (86) Заявка PCT: 2008051557 A2, 02.05.2008. US 20090274660 A1, 05.11.2009. RU 2002105502, 20.03.2004. В. М. Позняковский, Б.П. Суханов "Биологически активные добавки в современной нутрициологии", Техника и технология пищевых средств, N 2, 2009. ст. 1 Федерального закона "О качестве и безопасности пищевых продуктов" N 29-ФЗ от 02 (см. прод.) (87) Публикация заявки PCT: 2 6 4 2 9 6 4 WO 2013/174863 (28.11.2013) R U 2 6 4 2 9 6 4 (56) Список документов, цитированных в отчете о поиске: US 20110014308 A1, 20.01.2011. WO Приоритет(ы): (30) Конвенционный приоритет: R U 22.05.2013 (72) Автор(ы): ДЕ РОЗА Марио (CH), СКИРАЛЬДИ Кьяра (CH) Адрес для переписки: 191036, Санкт-Петербург, а/я 24, "НЕВИНПАТ" (54) ХОНДРОИТИН ДЛЯ ПРИМЕНЕНИЯ В МЕДИЦИНЕ (57) Реферат: Изобретение относится к фармацевтической содержащую эффективное количество промышленности и представляет ...

Carbohydrate cross-linking agent

FIELD: chemical or physical processes. SUBSTANCE: invention relates to production of glycosaminoglycan hydrogels. Disclosed hydrogel product contains glycosaminoglycan molecules as a swellable polymer. Glycosaminoglycan is selected from hyaluronic acid, heparosan and chondroitin sulphate. Molecules of glycosaminoglycans are covalently cross-linked, containing a spacer group selected from a group, consisting of di-, tri-, tetra- and oligosaccharides. Cross-linked glycosaminoglycan molecules do not contain synthetic non-carbohydrate structures or cross-linking agents. Method of preparing a hydrogel product comprising cross-linked glycosaminoglycan molecules selected from hyaluronic acid, heparosan and chondroitin sulphate, comprises providing a solution of glycosaminoglycan molecules; activation of carboxyl groups on molecules of glycosaminoglycan using a binding agent to form activated glycosaminoglycan molecules. Thereafter, the activated glycosaminoglycan molecules are cross-linked by their activated carboxyl groups using a di- or multinucleophilic functional cross-linking agent, containing a spacer group selected from a group consisting of di-, tri-, tetra- and oligosaccharides to form cross-linked glycosaminoglycans. Cross-linked glycosaminoglycans do not contain synthetic non-carbohydrate structures or cross-linking agents. Also disclosed is a method for cosmetic skin treatment using said hydrogel product. EFFECT: invention is aimed at obtaining a hydrogel product from glycosaminoglycan, which is closer in structure to natural molecules than hydrogel products known from the state of the art. 16 cl, 3 tbl, 6 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 733 145 C2 (51) МПК C08B 37/08 (2006.01) C08B 37/10 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C08B 37/0069 (2020.05); C08B 37/0072 (2020.05); C08B 37/0075 (2020.05) (21)(22) Заявка: 2018126372, 28.12.2016 (24) Дата начала отсчета срока действия ...

Способ расщепления амидных связей

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2018 126 365 A (51) МПК C09B 37/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2018126365, 28.12.2016 (71) Заявитель(и): ГАЛЬДЕРМА С.А. (CH) Приоритет(ы): (30) Конвенционный приоритет: EP EP EP EP (72) Автор(ы): ХАРРИС Крейг Стивен (FR), ЦЗИН ЦЗИН Лаура (FR) 15202944.3; 16172225.1; 16172241.8; 16172254.1 (43) Дата публикации заявки: 30.01.2020 Бюл. № 4 (86) Заявка PCT: EP 2016/082770 (28.12.2016) (87) Публикация заявки PCT: R U Адрес для переписки: 197101, Санкт-Петербург, А/я 128, "АРСПАТЕНТ", С. В. Новоселовой (54) СПОСОБ РАСЩЕПЛЕНИЯ АМИДНЫХ СВЯЗЕЙ (57) Формула изобретения 1. Способ расщепления амидных связей, включающий a) обеспечение молекулы, содержащей амидную группу, где амидная группа является первичной, вторичной или третичной амидной группой; b) проведение реакции молекулы, содержащей амидную группу, с гидроксиламином (NH2OH) или его солью для расщепления амидной связи амидной группы. 2. Способ по п. 1, отличающийся тем, что способ дополнительно включает: c) выделение продукта, образовавшегося в реакции стадии b). 3. Способ по п. 1 или 2, отличающийся тем, что амидная группа является Nациламидной группой, предпочтительно - N-ацетиламидной группой. 4. Способ по любому из пп. 1-3, отличающийся тем, что молекула, содержащая амидную группу, дополнительно содержит рН-чувствительный хиральный центр. 5. Способ по любому из пп. 1-4, отличающийся тем, что молекула, содержащая амидную группу, дополнительно содержит рН-чувствительную защитную группу. 6. Способ по любому из пп. 1-5, отличающийся тем, что стадия b) включает проведение реакции молекулы, содержащей амидную группу, с гидроксиламином или его солью при температуре, равной 100°С или менее. 7. Способ по любому из пп. 1-6, отличающийся тем, что стадия b) включает Стр.: 1 A 2 0 1 8 1 2 6 3 6 5 A WO 2017/114859 (06.07.2017) 2 0 1 8 1 2 6 3 6 5 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 30.07 ...

软骨素用于医学

软骨素是哺乳动物和其他活生物中硫酸软骨素合成的代谢中间物，具有不同于硫酸软骨素的生物学特性，可以有利地用于药物、营养制品、药用化妆品和医疗器械领域中的应用。软骨素具有生物刺激、抗炎和抗微生物活性，可以用于骨关节炎、眼障碍、间质性膀胱炎、肺障碍、一般炎性障碍、肿瘤学障碍的治疗，腹膜透析、组织生物复活和创伤修复，作为皮肤填充剂，及作为生物可吸收的支架。

光偶合协同交联水凝胶材料的制备、原料、产品及应用

本发明提供光偶合协同交联水凝胶材料的制备、原料、产品及应用。将组分A‑邻硝基苄基类光扳机修饰的高分子衍生物溶于生物相容性介质得到溶液A，将组分B‑含胺基类高分子衍生物或含双键类高分子衍生物或含巯基类高分子衍生物溶于生物相容性介质得到溶液B；将溶液A或加入溶液B混合均匀得到水凝胶前体溶液；水凝胶前体溶液在光源照射下，组分A中的邻硝基苄基在光激发下同时产生醛基/酮基或亚硝基进行双重交联，可以起到协同交联的效果。本发明还提供制备水凝胶用的试剂盒，以及水凝胶材料在组织工程和再生医学、3D打印及作为细胞、蛋白或药物载体上的应用。

光偶合协同交联水凝胶材料的制备、原料、产品及应用

本发明提供光偶合协同交联水凝胶材料的制备、原料、产品及应用。将组分A‑邻硝基苄基类光扳机修饰的高分子衍生物溶于生物相容性介质得到溶液A，将组分B‑含胺基类高分子衍生物或含双键类高分子衍生物或含巯基类高分子衍生物溶于生物相容性介质得到溶液B；将溶液A或加入溶液B混合均匀得到水凝胶前体溶液；水凝胶前体溶液在光源照射下，组分A中的邻硝基苄基在光激发下同时产生醛基/酮基或亚硝基进行双重交联，可以起到协同交联的效果。本发明还提供制备水凝胶用的试剂盒，以及水凝胶材料在组织工程和再生医学、3D打印及作为细胞、蛋白或药物载体上的应用。

Хондроитин для применения в медицине

1. Фармацевтическая композиция, содержащая несульфатированный хондроитин в качестве активного ингредиента.2. Композиция по п. 1 в форме капсул, таблеток, глазных капель, геля, кремов, растворов или суспензий, растворимых в полости рта порошков, спреев, сиропов.3. Композиция по п. 1 или 2, дополнительно содержащая другие активные ингредиенты.4. Композиция по п. 3, в которой несульфатированный хондроитин объединен с гиалуроновой кислотой.5. Нутрицевтическая композиция, содержащая несульфатированный хондроитин в качестве активного ингредиента.6. Композиция по п. 5 в форме капсул, таблеток, глазных капель, геля, кремов, растворов или суспензий, растворимых в полости рта порошков, спреев, сиропов.7. Композиция по п. 5 или 6, дополнительно содержащая другие активные ингредиенты.8. Композиция по п. 7, в которой несульфатированный хондроитин объединен с гиалуроновой кислотой.9. Космецевтическая композиция, содержащая несульфатированный хондроитин в качестве активного ингредиента.10. Композиция по п. 9 в форме капсул, таблеток, глазных капель, геля, кремов, растворов или суспензий, растворимых в полости рта порошков, спреев, сиропов.11. Композиция по п. 9 или 10, дополнительно содержащая другие активные ингредиенты.12. Композиция по п. 11, в которой несульфатированный хондроитин объединен с гиалуроновой кислотой.13. Медицинское устройство, содержащее несульфатированный хондроитин в качестве активного ингредиента.14. Медицинское устройство по п. 13, дополнительно содержащее другие активные ингредиенты.15. Медицинское устройство по п. 14, в котором несульфатированный хондроитин объединен с гиалуроновой кислотой.16. Применение несульфатированного хондроитина в качестве активного ингред РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2014 146 519 A (51) МПК A61K 31/726 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2014146519, 22.05.2013 (71) Заявитель(и): АЛЬТЕРГОН С.А. (CH) Приоритет(ы): (30) Конвенционный приоритет: 23.05. ...

Compositions and methods for treating joints

Compositions and methods are disclosed for the treatment of osteoarthritis. The compositions comprising combinations of hyaluronic acid, glucosamine, and chondroitin sulfate, can be useful for any synovial joint, including the knee, shoulder, hip, ankle, hands, spinal facet, or temporomandibular joint, both for the relief of pain and for slowing disease progression.

Patent RU2018126372A3

`7ВУ’” 2018126372” АЗ Дата публикации: 29.04.2020 Форма № 18 ИЗПМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2018126372/10(041775) 28.12.2016 РСТ/ЕР2016/082783 28.12.2016 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [ ] приоритета по первоначальной заявке № из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 15202944.3 29.12.2015 ЕР* 2. 16172225.1 31.05.2016 ЕР* 3. 16172241.8 31.05.2016 ЕР* 4. 16172254.1 31.05.2016 ЕР* Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) УГЛЕВОДНЫЙ СШИВАЮЩИЙ АГЕНТ Заявитель: ГАЛЬДЕРМА С.А., СН 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты (см. П см. Примечания [ ] приняты во внимание следующие пункты: р [ ] принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) СОЗВ 37/00 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) СО8В, Аб1К 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы данных, использованные при поиске (название базы, и если, возможно, поисковые термины): Езрасепе, Соозе, Соо]е Раеп$, РабеагсВ, эслепсе Ошесь Уапдех 6. ДОКУМЕНТЫ, ОТНОСЯЩИЕСЯ К ПРЕДМЕТУ ПОИСКА Кате- Наименование документа с указанием (где необходимо) частей, Относится к гория* ...

The method of purification of chondroitin sulfate

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2016 137 266 A (51) МПК C08B 37/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2016137266, 20.03.2015 (71) Заявитель(и): АЛЬТЕРГОН С.А. (CH) Приоритет(ы): (30) Конвенционный приоритет: 21.03.2014 IT MI2014A000486 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 21.10.2016 R U (43) Дата публикации заявки: 24.04.2018 Бюл. № 12 (72) Автор(ы): ДЕ РОЗА Марио (CH), СКИРАЛЬДИ Кьяра (IT) (86) Заявка PCT: (87) Публикация заявки PCT: WO 2015/140281 (24.09.2015) R U (54) Способ очистки хондроитин сульфата (57) Формула изобретения 1. Способ отделения хондроитин сульфата (ХС) и кератан сульфата (КС) от содержащего их водного раствора, включающий добавление в водный раствор смешиваемого с водой органического растворителя при условиях ионной силы, вызывающей образование двух жидких фаз: плотной фазы, в которой концентрируется ХС, и легкой фазы, где концентрируется КС. 2. Способ по п. 1, включающий: а) получение водного раствора ХС/КС и определение его проводимости, б) возможно добавление соли, способной к диссоциации на моно- или поливалентные ионы до предварительно установленного значения проводимости, в) постепенное добавление одного или более смешиваемых с водой органических растворителей, так чтобы вызвать фазовое разделение с концентрацией ХС в плотной фазе и КС в легкой фазе. 3. Способ по п. 1 или 2, в котором смешиваемые с водой органические растворители выбирают из метанола, этанола, 1-пропанола, 2-пропанола, 1-бутанола, 2-бутанола, ацетона, ацетонитрила или их смесей. 4. Способ по п. 3, в котором органическим растворителем является этанол или 2пропанол. 5. Способ по п. 1 или 2, в котором возможно добавляемая соль является хлоридом натрия. 6. Способ по п. 1, в котором процентную объемную долю каждого конкретного Стр.: 1 A 2 0 1 6 1 3 7 2 6 6 A Адрес для переписки: 191036, Санкт-Петербург, а/я 24, "НЕВИНПАТ" 2 0 1 6 1 3 7 2 6 6 EP 2015/055882 (20.03.2015) ...

Use of desulfated heparin

This invention relates to the use of desulfated heparins in which a sulfate group bound to a primary hydroxy group of the heparin is desulfated, for the manufacture of medicaments for the treatment of wounds, burns, dermal ulcers, osteoporosis, fractures or digestive ulcers. Preferably the desulfated heparin is obtainable by a process comprising recting a sulfated polysaccharide having a saccharide in which a primary hydroxyl group is sulfted, as a constituent sugar, with a silylating agent represented by the following formula (I) wherein R 1 s are the same or different and each represent a hydrogen atom or a halogen atom, R 2 represents an alkyl group having 1 to 6 carbon atoms, and R 3 s are the same or different and each represent an alkyl group having 1 to 6 carbon atoms, a phenyl group or a chlorine atoms or a fluorine atom, to selectively desulfate a sulfate group bonded to the primary hydroxyl group.

Process for producing desulfated polysaccharide, and desulfated heparin

A method of increasing proliferation of cells which comprises adding to cells a cellular proliferating amount of a primary hydroxyl group of N-acetylglucosamine selectively desulfated heparin having the following characteristics for an enzyme digestion product of the heparin: (1) contents of unsaturated disaccharides of the following formulae (a) and (b): measured by high performance liquid chromatography in the enzyme digestion product of the selectively desulfated heparin are less than 40% and 30 to 67%, respectively, (2) a content of disaccharides containing an N-substituted sulfate group is 75 to 95%, and (3) the weight average molecular weight Mw is 4,000 to 30,000 dalton.

Use of desulfated heparin

This invention relates to the use of desulfated heparins in which a sulfate group bound to a primary hydroxy group of the heparin is desulfated, for the manufacture of medicaments for the treatment of wounds, burns, dermal ulcers, osteoporosis, fractures or digestive ulcers. Preferably the desulfated heparin is obtainable by a process comprising recting a sulfated polysaccharide having a saccharide in which a primary hydroxyl group is sulfted, as a constituent sugar, with a silylating agent represented by the following formula (I) wherein R 1 s are the same or different and each represent a hydrogen atom or a halogen atom, R 2 represents an alkyl group having 1 to 6 carbon atoms, and R 3 s are the same or different and each represent an alkyl group having 1 to 6 carbon atoms, a phenyl group or a chlorine atoms or a fluorine atom, to selectively desulfate a sulfate group bonded to the primary hydroxyl group.