HAPTEN AND MURAMYLPEPTIDKONJUGATE, WITH IMMUNOGENI EFFECTIVENESS AND THE SAME CONTAINING PREPARATIONS.

OLIGO MURAMYLPEPTIDE CONTAINING PREPARATIONS AND YOUR USE, IN PARTICULAR FOR THE ACTIVATION OF MACRO PHAGES.

PROCEDURE FOR THE PRODUCTION OR CLEANING OF AN SLEEP-INDUCING MATERIAL FROM A BIOLOGICAL MEANS BY IMMUNOLOGICAL REACTION OF THE KIND OF ANTIGEN ANTI-BODY.

(Pasteurella Haemolytica) subunit vaccine containing capsularpolysaccharide and muramyl dipeptide

CONJUGATES OF MURAMYL-PEPTIDES AND HAPTENES

The invention relates to an immunogenic principle containing a specific antigen determinant of a predetermined native antigen. This immunogenic principle is constituted by a conjugate between a hapten bearing said antigenic site and a muramyl-peptide, essentially in the absence of supporting macromolecules, this conjugate having an immunogenic effect not only against itself, but also with respect to the native antigen carrying said antigenic site.

Process for the preparation of 2-(2-acetamido-2-deoxy-3-O-D-glucopyranosyl)-D-propionyl-L-seryl-D-iso glutamine and 2-(2-acetamido-2-deoxy-3-O-D-glucopyranosyl)-D-propionyl-L-seryl-D-glu tamic acid

The compounds indicated are obtained by peptide linkage starting with the optionally esterified or amidated chain L-seryl-D-(iso)glutamine and an N-acetylmuramic acid derivative, any group which should not react being temporarily blocked. A variant consists in coupling, using the same reaction, L-serine with N-acetylmuramic acid and then with D-isoglutamine or D-glutamic acid, and the esters or amides thereof. The water-soluble compounds thus obtained are non-toxic potent immunological adjuvants.

Process for the preparation of the esters of N-acetyl-muramyl-L-alanyl-D-glutamic acid and of N-acetyl-muramyl-L-alanyl-D-isoglutamine

These compounds which correspond to the formula I where R1 = -NH2 or -OCnH2n+1 (n = 1, 2 or 3), R2 = -OCpH2p+1 and p = 0, 1, 2 or 3, p NOTEQUAL 0 when R1 = -NH2, are prepared by peptide linkage starting with the two amino acids or even the dipeptide L-Ala-D-Glu or L-Ala-D-iso-Gln. The compounds obtained are useful as anti-infectious agents or immune adjuvants. <IMAGE>

OLIGOMERIC COMPOUNDS SUCH AS MURAMYL-PEPTIDE AND MEDICAMENTS CONTAINING THEM.

2- [...] DE [...] DE LA (P-AMINO-PHENYL-2-2 - 3-0-D-GLUCOPYRANOSYL ACETAMIDO-DEOXY-)-D-PROPIONYL-L-ALANYL-D- iSO GLOW AMINES.

Compositions based on hydrophobic substances and which can be solubilised in an aqueous solvent, process for obtaining them and their uses, in particular in the pharmaceutical field

The invention relates to any composition which comprises: - on the one hand a water-insoluble pharmacologically active substance, this substance being substituted with a lipid A or a derivative of lipid A, and - on the other hand a glycoside derivative, at least one of the hydroxyl functions of which is substituted with one or more phosphate or sulphate group(s), this compound also being substituted with a lipophilic group, this composition being capable of being solubilised or dispersed homogeneously in an aqueous solvent. The invention also relates to the use of such compositions, in particular as pharmaceutical compositions dissolved in a physiologically acceptable aqueous solvent.

MITOGENE MITTEL, DIE INSBESONDERE VON BAKTERIEN-PEPTIDOGLYKANEN STAMMEN

Immunogical adjuvants for weak vaccine antigens - are (2)-acetamido-deoxy (D)-glucopyranosyl (D)-propionyl (L)-alanyl (D)-glutamic acid esters and (D)-isoglutamines

... 2-(2-acetamido-2-deoxy-3-O-D-glucopyranosyl)-D-propionyl-L-alanyl- -D-glutamic acid esters and 2-(2-acetamido-2-deoxy-3-O-D-glucopyranosyl)-D-propionyl-L-alanyl- -D-isoglutamine of formula (I) are novel cpds. (where R1 = -OCnH2n+1 or -NH2; n = 1, 2 or 3; R2 = O-CpH2p+1 and p = 0, 1, 2 or 3 with the condition that p - O when R1 = -NH2). Cpds. (I) are anti-infectious agents and immunological adjuvants used to stimulate an innumitary response in a host to bacterial, viral and parasitory infections and against different tissular antigens. When using (I) it is not necessary to use a particular admin. medium e.g. for injectable solutions it is not necessary to have an oil phase. (I) may be administered by oral, parenteral (injection) or scarification methods or by application to mucous tissues. (I) have low toxicity and are well tolerated when administered parenterally to mice at 100 mg/kg and rabbits at 5 mg/kg. Their admin. with weak vaccine antigens is claimed.

WATER-SOLUBLE IMMUNOLOGICAL ADJUVANTS

WATER-SOLUBLE IMMUNOLIGICAL ADJUVANTS WATER-SOLUBLE IMMUNOLIGICAL ADJUVANTS

Mdp derivatives and conjugates having haematopoietic functio n stimulating activity, and compositions containing same

WASSERLOESLICHES IMMUNOLOGISCHES ADJUVANS

Derivate von Muramyldipeptid.

COMPOSITIONS FOR APPLICATION IN HUMAN THERAPY, CHARACTERIZES BY THE ASSOCIATION OF A MURAMYLPEPTIDS WITH A CYTOKIN

LIPOPHILIC MURAMYLPEPTID DERIVATIVES WITH MACRO PHAGES AN ACTIVATING EFFECT, IT CONTAINING COMPOSITIONS AND PROCEDURES FOR YOUR PRODUCTION.

OIL-FREE ADJUVANT COMPOSITIONS

PROCESS FOR THE SEPARATION OF LYMPHOCYTE ACTIVATING FACTORS FROM INCUBATION MEDIA OF CELL POPULATIONS, PARTICULARLY FROM A GRANULOCYTE-MACROPHAGIC LINE, BY AN ANTIGEN-ANTIBODY REACTION UTILIZING ANTI-MDP ANTIBODIES

PROCESS FOR THE SEPARATION OF LYMPHOCYTE ACTIVATING FACTORS FROM AN INCUBATION MEDIUM OF CELL POPULATIONS, PARTICULARLY FROM A GRANULOCYTE-MACROPHAGIC LINE, BY AN ANTIGEN-ANTIBODY REACTION UTILIZING ANTI-MDP ANTIBODIES The invention relates to a process for the separation or purification of a factor, having lymphocyte activating properties and, as the case may be, pyrogenicendogenous properties. It comprises contacting said medium with anti-MDP antibodies and recovering either the complex then formed of said factor and of the anti-MDP antibodies or the medium then substantially freed from said factor.

MDP DERIVATIVES AND CONJUGATES HAVING HAEMATOPOIETIC FUNCTION STIMULATING ACTIVITY, AND COMPOSITIONS CONTAINING SAME

A pharmaceutical composition for stimulating the haematopoietic function and preventing the myelotoxic side-effects of some treatments, containing at least one water-soluble muramyl peptide derivative such as Muradimetide, muroctasine or MTP-PE.

PROCEDURE FOR THE PRODUCTION STURDY WATER - IN-OIL-EMULSION FOR THE PREPARATION OF ADJUVANSPRAEPARATEN FOR VACCINES AND/OR OF VACCINES

DERIVATIVES OF MURAMYLDIPEPTID.

DERIVATIVES AND A OF HÄMATOPOITI FUNCTION STIMULATING EFFECT AND THEIR CONTAINING COMPOSITIONS KONJUGETE FROM MDP,

2-(2-ACETAMIDO2-DEOXY-3-O-D-GLUCOPYRANOSY)-D- PROPIONYL-L-SERYL-D-ISOGLUTAMINE, 2-(2-ACETAMIDO-2- DEOXY-3-O-D-GLUCOPYRANOSYL)-D-PROPIONYL-L-SERYL-D- GLUTAMIC ACID, ESTER AND AMIDE DERIVATIVES THEREOF, AND MEDICAMENTS CONTAINING THEM

OF THE DISCIOSURE The invention relates to new water-soluble agents which are effective as immunising adjuvants. These adjuvant agents are the 2-(2-acetamido-2-deoxy-3-O-D-glucopyranosyl)-D-propionyl-L-seryl-D-isoglutamine, the 2-(2-acetamido-2-deoxy-3-O-D-glucopyranosyl)-D-propionyl-L-seryl-D-glutamic acid and their derivatives. These agents are particularly useful to prepare adjuvant medicinal compositions used for increasing the efficiency of vaccines.

PROCESS FOR PREPARING CONJUGATED HAPTENS AND MURAMYL-PEPTIDES USEFUL AS IMMUNOGENIC AGENTS, AND COMPOSITIONS CONTAINING THE SAME

Procédé de préparation d'un conjugué de muramylpeptide et d'un haptène, ce conjugué étant dépourvu de pyrogénicité et n'induisant pas in vivo d'anticorps actifs contre la partie muramyl-peptide du conjugué, caractérisé par une réaction de condensation entre les deux partenaires que constituent l'haptène et le muramyl-peptide, l'un de ces partenaires étant pourvu d'une fonction aminée et l'autre de ces partenaires étant pourvu d'une fonction complémentaire carboxyle, ester, alcool, sulfhydryle ou amine, la réaction étant conduite en présence d'un agent de condensation entre la fonction aminée du premier partenaire et la fonction carboxyle, ester, alcool, sulfhydryle ou amine du second partenaire, et en ce que l'haptène présente un poids moléculaire ne dépassant pas environ 5000.

Increasing immunogenicity of alum-contg. vaccine

Vaccine contg. an antigen absorbed on alum or formulated in an alum-contg. compsn. and having greater immunogenicity than known vaccines contains 2-120 mu g/kg body wt. or 0.1-6 mg/dose of a muramyl peptide of formula (I) or MDP-Lys-GDP (II, NAc-Mur-L- Lys-D-isoGln-glyceryl-sn-dipalmitoyl). R = H or Me; X = L-Ala or L-Thr, and R1,R2 = OH, NH2 or 1-4C alkoxy, \-1 must be alkoxy when X = L-Ala. Also claimed is a method for the prepn. of a vaccine as above.

PROCESS OF SEPARATING OR PURIFYING A SLEEP PROMOTING FACTOR FROM A BIOLOGICAL MEDIUM BY AN IMMUNOLOGICAL REACTION OF THE ANTIGEN-ANTIBODY TYPE

PROCESS OF SEPARATING OR PURIFYING A SLEEP PROMOTING FACTOR FROM A BIOLOGICAL MEDIUM BY AN IMMUNOLOGICAL REACTION OF THE ANTIGEN-ANTIBODY TYPE. The invention relates to a process of separating or purifying a sleep-promoting factor("S" factor) from a biological medium, such as urine, which contains it. This process comprises contacting said medium with anti-MDP antibodies and recovering the "S" factor from the "S" factor-anti-MDP antibody complex, by dissociation thereof.

COMPOSITIONS BASED ON ACTIVE INGREDIENTS OF HYDROPHOBIC DRUGS THAT CAN BE SULUBILIZED IN AN AQUEOUS SOLVENT

... 2087536 9201475 PCTABS00110 L'invention concerne toute composition caractérisée en ce qu'elle comprend: d'une part, un principe actif de médicament ou substance pharmacologiquement active, insoluble dans l'eau, cette substance étant substituée par au moins un groupement lipophile, et d'autre part, un dérivé osidique dont l'une au moins des fonctions hydroxyles est substituée par un ou plusieurs groupe(s) phosphate ou sulfate, ce composé étant également substitué par un groupement lipophile, cette composition étant susceptible d'être solubilisée ou dispersée de façon homogène dans un solvant aqueux. L'invention concerne également l'utilisation de telles compositions, notamment en tant que compositions pharmaceutiques en solution dans un solvant aqueux physiologiquement acceptable.

Prevention and treatment of septic syndrome with an immunosuppressant, in particular cyclosporin.

L'invention concerne l'utilisation d'un immunosuppresseur efficace chez l'homme pour la production d'un médicament pour prévenir ou traiter les manifestations cliniques du syndrome septique.

VERFAHREN ZUR HERSTELLUNG EINES MITTELS MIT MITOGENEN UND/ODER ADJUVANS-EIGENSCHAFTEN UND DIESES MITTEL ENTHALTENDE ARZNEIMITTEL

NOVEL COMPOUNDS OF THE MURAMYL-PEPTIDE TYPE

COMPOSITIONS OF VACCINES CONDITIONED FOR THE VACCINATION OF IMMUNITARILY NON-NAIVE SUBJECTS AGAINST A PREDETERMINED PATHOGENIC AGENT AND CONTAINING A HAPTENE ITSELF COMPRISING AN ANTIGENIC SITE CHARACTERISTIC OF SAID PATHOGENIC AGENT OR AN OLIGOMER

COMPOSITIONS OF VACCINES CONDITIONED FOR THE VACCINATION OF IMMUNITARILY NON-NAIVE SUBJECTS AGAINST A PREDETERMINED PATHOGENIC AGENT AND CONTAINING A HAPTENE ITSELF COMPRIS-ING AN ANTIGENIC SITE CHARACTERISTIC OF SAID PATHOGENIC AGENT OR AN OLIGOMER OF THIS HAPTENE ABSTRACT OF THE DISCLOSURE The invention relates to a vaccine composition against a predetermined pathogenic agent suitable for the reimmunization of an immunitarily non-naive host. It con-tains a synthetic haptene possessing itself an antigenic site characteristic of said pathogenic agent or an oli-gomer of said haptene. It is conditioned in dose-units containing a dosage of haptene adjusted for said re-immu-nization of the immunitarily non-naive subject, in asso-ciation with a physiologically acceptable vehicle. (no drawing)

OIL-FREE ADJUVANT COMPOSITION CONTAINING MURAMYL DIPEPTIDE

The invention relates to an oil-free adjuvant composition, containing N-acetyl-muramyl-L-alanyl-D-glutamic acid as an active principle, associated to a pharmaceutically acceptable vehicle. This composition can act as an immunological adjuvant to stimulate a host's immunitary response to different sorts of antigens.

PASTEURELLA HAEMOLYTICA SUBUNIT VACCINE CONTAINING CAPSULAR POLYSACCHARIDE AND MURAMYL DIPEPTIDE

Protection of ruminants against bacterial pneumonia caused by Pasteurella haemolytica has been achieved with a subunit vaccine. The vaccine contains two principle components; capsular polysaccharide of P. haemolytica and a synthetic adjuvant, muramyl dipeptide. This vaccine prevented bacterial infection of the lungs of vaccinated animals upon challenge with P. haemolytica. In contrast, animals that were not vaccinated or animals that were vaccinated with only capsular polysaccharide alone had severe lesions and high concentrations of P. haemolytica in the lungs.

Diesters of muramyl peptides in an oral form

L'invention concerne une composition pharmaceutique immunostimulante active par voie externe, caractérisée en ce qu'elle contient un diester de formule générale I: (CF DESSIN DANS BOPI) dans laquelle: - R est CH3, - X est L-Ala ou L-Thr, - R1 est un groupe hydrocarboné possédant de 1 à 4 atomes de carbone, - R2 est un groupe hydrocarboné possédant 1 à 2 atomes de carbone, dans une formulation d'administration par voie externe compatible avec une administration de principe actif comprise entre 0,1 mg et 5 mg par kg de poids chez l'homme ou l'animal.

Compositions for application in human therapeutics, characterised by the combination of a muramylpeptide with a cytokine

The invention relates to a composition combining, for the purposes of their application in human therapeutics, a natural or recombinant, preferably human, cytokine with a muramylpeptide. It can be used for antiviral or antitumour therapies and/or for promoting reconstitution of the haematopoietic system, especially in people whose immune system is or has been rendered deficient.

ENHANCED IMMUNOGENIC VACCINE

Vaccins composés d'antigènes absorbés sur alum ou formulés dans une composition contenant de l'alum présentant une immunogénicité accrue comparée à celle des vaccins existant et caractérisés en ce qu'ils sont associés à 10 à 200 mug par kg et par dose préférentiellement entre 40 et 160 mug par kg et par dose et encore préférentiellement 80 à 120 mug par kg et par dose vaccinante d'un muramyl peptide hydrosoluble. Vaccines composed of antigens absorbed on alum or formulated in a composition containing alum exhibiting increased immunogenicity compared to that of existing vaccines and characterized in that they are associated with 10 to 200 mug per kg and per dose preferably between 40 and 160 μg per kg and per dose and more preferably 80 to 120 μg per kg and per vaccinating dose of a water-soluble muramyl peptide.

Enhanced immunogenic vaccine

COMPOSITIONS FOR USE IN HUMAN THERAPEUTICS, CHARACTERISED BY THE ASSOCIATION OF A MURAMYL PEPTIDE WITH A CYTOKINE

A therapeutical composition for use in humans, comprising a combination of at least one natural or recombinant and preferably human cytokine with at least one muramyl peptide selected from those which, when administered in vivo together with an interferon, also induce an increased in vivo production of an interleukin-1 receptor antagonist IL-1 RA, but preferably do not induce any increase in TNF, IL-8 and IL-1 cytokines. Said composition is useful for antiviral and antitumoral therapies and/or for promoting restoration of the haematopoietic system, particularly in individuals with a weakened immune system.

IMMUNISING AND ANTI-INFECTIOUS ADJUVANT AGENTS CONSTITUTED BY ESTERS OF THE N-ACETYL-MURAMYL-L- ALANYL-D-ISOGLUTAMINE

The invention relates to new water-soluable agents which are effective as immunising adjuvants. These adjuvant agents are the methyl, ethyl or propyl esters of 2-(2-acetamido-2-deoxy-3-0-D-glucopyranosyl)-D-propionyl-L-alanyl-D-isoglutamine and of 2-(2-aceramido-2-deoxy-3-0-D-glucopyranosyl)-D-propionyl-L-alanyl-D-glutamic acid. They are particularly useful to prepare adjuvant medicinal compositions, used for increasing the efficiency of vaccines.

Auxiliary composition of immunity humorale and with cellular mediation not inducing a réponsevis-with-screw of car-antigenic determinants

L'invention est relative à un procédé de préparation d'une composition pharmaceutique exerçant une action adjuvante sélective de l'immunité mettant en œuvre une réponse humorale ou une réponse à médiation cellulaire, de préférence les deux à la fois, à l'encontre d'antigènes déterminés, en l'absence de toute induction de maladie auto-immune liée à une réponse vis-à-vis de déterminants auto-antigéniques. Le principe adjuvant de cette composition pharmaceutique est constitué par le MDP-DD-GDP de formule: (CF DESSIN DANS BOPI)

NOVEL COMPOUNDS OF THE MURAMYL-PEPTIDE TYPE

Therapeutical compositions for use in humans, characterised by a combination of a muramyl peptide and a cytokine

DERIVES LIPOPHILES DE MURAMYLPEPTIDES AYANT DES PROPRIETES D'ACTIVATION DES MACROPHAGES, COMPOSITIONS LES CONTENANT ET PROCEDE POUR LES OBTENIR

Dérivés lipophiles de muramylpeptides ayant des propriétés d'activation des macrophages compositions les contenant et procédé pour les obtenir. ABR?G? L'invention concerne des dérivés de muramylpeptides résultant essentiellement de la conjugaison ou du couplage, le cas échéant par l'intermédiaire d'un bras, entre un muramylpeptide et un groupe contenant deux atomes contigus l'un à l'autre sur chacun desquels est branchée une chaîne lipophile comprenant de 8 à 100 atomes de carbone, de préférence de 14 à 24 atomes de carbone. Les dérivés selon l'invention sont doués de remarquables propriétés stimulantes à l'égard de l'activation des macrophages, dont ils amplifient les propriétés tumoricides.

OIL-FREE ADJUVANT COMPOSITION CONTAINING MURAMYL DIPEPTIDE

A B S T R A C T The invention relates to an oil-free adjuvant compo-sition, containing N-acetyl-muramyl-L-alanyl-D-isoglutamine as an active principle, associated to a pharmaceutically accepta-ble vehicle. This composition can act as an immunological adjuvant to stimulate a host's immunitary response to different sorts of antigens.

Compositions for application in human therapeutics, characterised by the combination of a muramylpeptide with a cytokine

The invention relates to a composition combining, for the purposes of their application in human therapeutics, a natural or recombinant, preferably human, cytokine with a muramylpeptide. It can be used for antiviral or antitumour therapies and/or for promoting reconstitution of the haematopoietic system, especially in people whose immune system is or has been rendered deficient.

Immunomodulatory compositions based on products containing at least one phosphated or sulphated group and a gel of an aluminium compound

L'invention concerne une composition immunomodulatrice ayant une capacité immunostimulatrice accrue, tant au niveau humoral que cellulaire. Cette composition contient d'une part, un immunomodulateur destinés à stimuler la réponse immune non spécifique (notamment agent anti-infectieux), ou en présence d'une substance immunisante, à stimuler la réponse immune spécifique (adjuvant de vaccin), ou les deux à la fois, cet immunomodulateur étant sous forme soluble dans l'eau ou solubilisable dans l'eau, le cas échéant en présence d'un dispersif et susceptible de se lier à l'immunomodulateur par des liaisons non covalentes et, d'autre part, un gel d'un composé d'aluminium, cette composition étant caractérisée par la présence de groupes sulfate ou phosphate soit sur l'immunomodulateur lui-même, soit, lorsque celui-ci est présent, sur le dispersif du genre en question. L'invention concerne enfin les préparations pharmaceutiques contenant la susdite composition et dépourvues de constituants huileux ...

ZUSAMMENSETZUNGEN FÜR DIE ANWENDUNG IN MENSCHLICHER THERAPIE, CHARAKTERISIERT DURCH DIE ASSOZIATION EINES MURAMYLPEPTIDS MIT EINEM CYTOKIN

ANTI-INFECTIOUS AGENT ALPHA-METHYL ESTERS

(pasteurella haemolytica) subunit vaccine containing capsular polysaccharide and muramyl dipeptide

VACCINES CONDITIONED FOR VACCINATION OF IMMUNITARILY NON-NAIVE SUBJECTS

COMPOUNDS OF THE MURAMYL-PEPTIDE TYPE AND MEDICAMENTS CONTAINING THEM

IN THE CANADIAN PATENT OFFICE PATENT APPLICATION entitled Novel compounds of the muramyl-peptide type and medicaments containing them in the name of : AGENCE NATIONALE DE VALORISATION DE LA RECHERCHE (A N V A R) The compounds have the structure 2-(2-amino or alkylamido-2-desoxy-3-O-D-glucopyranosyl)-alkanyl-dipeptide, possibly substituted on the saccharide residue, the amino acid residue at the end of the peptide chain being a D-glutamyl residue whose .alpha.-carboxy function is esterified and ?-carboxyl function amidated. The compounds are valuable as immunological medicaments.

USE OF DIESTERS OF MURAMYL PEPTIDES IN ORAL FORM AS IMMUNOSTIMULATING AGENTS

L'invention concerne une composition pharmaceutique immunostimulante active par voie externe, caractérisée en ce qu'elle contient un diester de formule générale (I) dans laquelle: R est CH3, X est L-Ala ou LThr, R1 est un groupe hydrocarboné possédant de 1 à 4 atomes de carbone, R2 est un groupe hydrocarboné possédant 1 à 2 atomes de carbone, dans une formulation d'administration par voie externe compatible avec une administration de principe actif comprise entre 0,1 mg et 5 mg par kg de poids chez l'homme ou l'animal.

MURAMYL DIPEPTIDE DERIVATIVES

... 900-9576 : MURAMYL DIPEPTIDE DERIVATIVES The 3-0-¢N-acetylmuramyl-D-isoglutaminyl!-1,2-di-O-palmitoyl-sn-glycerol derivative of formula I I wherein the carbon atom marked with an asterisk * has the R or, respectively, the S configuration, possesses interesting pharmacological, in particular immunomodulating properties. It is particularly indicated for use as an immunomodulant, as an adjuvant in vaccines and as a suppressing agent for IgE formation in e.g. type I allergies and atopical dermatitises. It is obtained by deprotection of a corresponding compound having one or more hydroxy groups(s) in protected form. 6300/VA 1446 VASP13/VASP23 ...

HUMORAL IMMUNITY AND CELL MEDIATION ADJUVANT COMPOSITION INDUCING NO RESPONSE TO AUTO-ANTIGENIC DETERMINANTS

L'invention est relative à un procédé de préparation d'une composition pharmaceutique exerçant une action adjuvante sélective de l'immunité mettant en oeuvre une réponse humorale ou une réponse à médiation cellulaire, de préférence les deux à la fois, à l'encontre d'antigènes déterminés, en l'absence de toute induction de maladie auto-immune liée à une réponse vis-à-vis de déterminants auto-antigéniques. Le principe adjuvant de cette composition pharmaceutique est constitué par le MDP-DD-GDP de formule (I). The invention relates to a process for the preparation of a pharmaceutical composition exerting a selective adjuvant action of immunity using a humoral response or a cell-mediated response, preferably both at the same time, against 'antigens determined, in the absence of any induction of autoimmune disease linked to a response vis-à-vis autoantigenic determinants. The adjuvant principle of this pharmaceutical composition consists of the MDP-DD-GDP of formula (I).

ENHANCED IMMUNOGENIC VACCINE

Vaccines, composed of antigens absorbed on alum or formulated in an alumcontaining composition, have enhanced immunogenicity over existing vaccines. The vaccines of the invention are characterized by their combination with 2120 .mu.g per kg or 0.1-6 mg by dose, preferentially 6-60 .mu.g per kg or 0.33 mg by dose of a hydrosoluble muramyl peptide.

EMULSIONS OF VEGETABLE OIL AND WATER

ABSTRACT OF THE DISCLOSURE Water-in-oil emulsion formed from a metabolisable vegetable oil and water, the emulsion containing less water than oil and protein in a quantity suitable to ensure the stability of the emulsion ; adjuvant composition which contains such an emulsion and an adjuvant agent of the water-soluble fraction type, the principal constituent of which is formed by peptidoglycane of bacteria or by a fragment of peptidoglycane, or by N-acetyl-muramyl-L-alanyl-D-isoglutamine or an analogue thereof ; a composition of the vaccine type containing a vaccinating antigen in solution or suspension in one at least of the constituents of such an emulsion ; and a presentation in the form of a "kit" or analoque of an injec-table liquid medium form from water or physiological serum metabolisable vegetable oil non-immunogenic protein in which the various constituents are presented in bottles or receptacles which are separate or not in predetermined volumes or weights as a function of the proportions defined above.

Compositions based on hydrophobic substances and which can be solubilised in an aqueous solvent, process for obtaining them and their uses, in particular in the pharmaceutical field

The invention relates to any composition which comprises: - on the one hand a water-insoluble pharmacologically active substance, this substance being substituted with at least one lipophilic group, and - on the other hand a glycoside derivative, at least one of the hydroxyl functions of which is substituted with one or more phosphate or sulphate group(s), this compound also being substituted with a lipophilic group, this composition being capable of being solubilised or dispersed homogeneously in an aqueous solvent. The invention also relates to the use of such compositions, in particular as pharmaceutical compositions in solution in a physiologically acceptable aqueous solvent.

MDP DERIVATIVES AND CONJUGATES HAVING HAEMATOPOIETIC FUNCTION STIMULATING ACTIVITY, AND COMPOSITIONS CONTAINING THEM

A pharmaceutical composition for stimulating the haematopoietic function and preventing the myelotoxic side-effects of some treatments, containing at least one water-soluble muramyl peptide derivative such as Muradimetide, muroctasine or MTP-PE.

Use of lipophilic muramyl peptide MDP:DD:GPD - in vaccines against HIV and tumours

Pharmaceutical compsn. contg. MDP-DD-GDP (I) are new., The compns. are pref. prepd. as vaccines contg. pathogenic agents, particularly human or mammnalian viruses or virus fractions. The prepn. of compsn. against HIV and tumours is esp. pref.. The compsns. are pref. biphasic, an aqueous phase and a hydrophobic phase. The hydrophobic phase may be a mineral oil, lipids, polyoxylene- polyoxypropylene polymers, polyoxyethylene sorbitan esters. USE - The compsns. exert a selective adjuvant action on the humoral or cellular mediation immunity response, or pref. both of these, without inducing auto-immune disorders. The action is similar to that of Freund's complete adjuvant, but without inducing the known side effects of this.

NEW COMPOUNDS ASSOCIATING PEPTIDYL OR AMINOACYL RESIDUES TO LIPOPHILIC GROUPS AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAID NEW COMPOUNDS

IMPROVEMENTS IN OR RELATING TO ORGANIC COMPOUNDS

CONJUGATES OF MURAMYL-PEPTIDES AND HAPTENES

AUS N-ACYL-MURAMINSAEUREDERIVATEN GEBILDETE ADJUVANZIEN UND DIESE ENTHALTENDE IMPFSTOFFE

COMPOSITIONS BASED ON ACTIVE PRINCIPLES OF HYDROPHOBIC MEDICAMENTS SOLUBILIZABLE IN AN AQUEOUS SOLVENT

2-(2-ACETAMIDO-2-DESOXY-3-0-D-GLUCOPYRANOSYL)-D-PROPIONYL-L-SERYL-ISOGLUTAMIN, 2-(2-ACETAMIDO-2-DESOXY-3-0- D-GLUCOPYRANOSYL)-D-PROPIONYL-L-SERYL- D-GLUTAMINSAEURE, DIE AMID- UND ESTER- DERIVATE DIESER VERBINDUNGEN, VERFAHREN ZU IHRER HERSTELLUNG UND DIESE VERBINDUNGEN ALS WIRKSTOFFE ENTHALTENDE ARZNEIMITTEL

Use of diesters of muramyl peptides in oral form as immunostimulating agents

Humoral immunity and cell mediation adjuvant composition inducing no response to auto-antigenic determinants

WASSERLOESLICHE ADJUVANTIEN, VERFAHREN ZU IHRER HERSTELLUNG UND SIE ENTHALTENDE ARZNEIMITTEL

OLIGOMERE VON MURAMYLPEPTIDARTIGEN VERBINDUNGEN UND SIE ENTHALTENDE ARZNEIMITTEL

DERIVATE UND KONJUGETE VON MDP, EINE VON HÄMATOPOITISCHER FUNKTION STIMULIERENDE WIRKUNG UND DEREN ENTHALTENDE ZUSAMMENSETZUNGEN

N-ACETYL-MURAMYL-L-ALANYL-D-ISOGLUTAMIN ENTHALTENDE OELFREIE ADJUVANZIEN

LIPOPHILE MURAMYLPEPTID-DERIVATE MIT EINER MAKROPHAGEN AKTIVIERENDEN WIRKUNG, DIE SIE ENTHALTENDEN ZUSAMMENSETZUNGEN UND VERFAHREN ZU IHRER HERSTELLUNG.

2-(2-ACETAMIDO-2-DESOXY-3-0-GLUCOPYRANOSYL)-D-PROPIONYL-L-ALANYL-D-GLUTAMINSAEURE-(ALPHA-METHYLAMID), VERFAHREN ZU SEINER HERSTELLUNG UND DIESE VERBINDUNG ENTHALTENDE ARZNEIMITTEL

CONJUGATES OF HAPTENES AND MURAMYL PEPTIDES HAVING AN IMMUNOGENIC ACTIVITY, AND COMPOSITIONS CONTAINING THEM

N-ACETYL-MURAMYL-L-ALANYL-D-GLUTAMINSAEURE ENTHALTENDE OELFREIE ADJUVANZIEN

DERIVATE UND KONJUGETE VON MDP, EINE VON HÄMATOPOITISCHER FUNKTION STIMULIERENDE WIRKUNG UND DEREN ENTHALTENDE ZUSAMMENSETZUNGEN

MURAMYL-PEPTIDE ESTER DERIVATIVES AND THEIR APPLICATION TO PHARMACOLOGICAL COMPOSITIONS AND LABORATORY REACTANTS

P-AMINO-PHENYL-N-ACETYL-MURAMYL-L- ALANYL-D-ISOGLUTAMIN, VERFAHREN ZU DESSEN HERSTELLUNG UND DIESE VERBINDUNG ENTHALTENDE ARZNEIMITTEL

PROCESS FOR THE SEPARATION OR PURIFICATION OF A SLEEP PROMOTING FACTOR FROM A BIOLOGICAL SOURCE BY IMMUNOLOGICAL REACTION OF THE ANTIGEN-ANTIBODY KIND

Derivate von Muramyldipeptid.

COMPOSITIONS CONTAINING OLIGO-MURAMYLPEPTIDES AND THEIR APPLICATION, IN PARTICULAR FOR THE ACTIVATION OF MACROPHAGES

AUS MIKROORGANISMEN VON DER ART DER MYCOBAKTERIEN ERHALTENE, NICHT-SPEZIFISCHE REIZMITTEL, DIE EINE ANTITUMORIMMUNITAET HERVORRUFEN UND VERFAHREN ZU DEREN HERSTELLUNG

MURAMYL PEPTIDES FIXED ON PEPTIDE POLYMERS AND MEDICAMENTS CONTAINING THEM

EMULSION AUF DER GRUNDLAGE EINES STOFFWECHSELFAEHIGEN PFLANZLICHEN OELS UND WASSER

N-ACETYL-L-(N-METHYL-ALANIL)-D-ISOGLUTAMINE AND COMPOSITIONS CONTAINING IT FOR USE AS REGULATOR OF THE IMMUNE REACTIONS

MITOGENES MITTEL, VERFAHREN ZU SEINER HERSTELLUNG UND DIESE MITTEL ENTHALTENDE ARZNEIMITTEL UND BIOLOGISCHE REAGENZIEN

VERFAHREN ZUR DARSTELLUNG NEUER VERBINDUNGEN DES MURAMYLPEPTIDTYPS

ZUSAMMENSETZUNGEN FÜR DIE ANWENDUNG IN MENSCHLICHER THERAPIE, CHARAKTERISIERT DURCH DIE ASSOZIATION EINES MURAMYLPEPTIDS MIT EINEM CYTOKIN

MDP DERIVATIVE AND CONJUGATE HAVING HEMATOPOIETIC FUNCTION-STIMULATING ACTIVITY, AND COMPOSITION CONTAINING THE SAME

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition capable of mobilizing a large amount of stem cells derived from the bone marrow and forming the stem cells in the blood flow by stimulating hematopoietic function. SOLUTION: The pharmaceutical composition contains at least one of water-soluble muramyl peptide derivatives such as muradimetide, muroctasine and MTP-PE, and is used for stimulating the hematopoietic function, and preventing the bone marrow toxicity effects caused by some kinds of treatments. The pharmaceutical composition is preferably prepared so that 0.1-25 mg dose per kg human body weight can be orally administered. COPYRIGHT: (C)2006,JPO&NCIPI ...

MURAMYL DIPEPTIDE DERIVATIVES

NEW MATERIAL: A compound of formula I in the various forms (the carbon atom with an asterisk * has the R or S configuration). USE: Adjuvant in vaccines. PROCESS: For example, N-benzyloxycarbonyl-D-isoglutamine is reacted with 1,2-dipalmitoyl-sn-glycerine to give a compound of formula II (R' is benzyloxycarbonyl) and the amino-protecting group is made to lieve. The resultant deblocked product is reacted with a protected threonine of the formula BOC-Thr(Bzl)-OH (BOC is t-butoxycarbonyl; Bzl is benzyl) to give a compound of formula III. The product is then reacted with a protected muramic acid of formula IV (R1 to R3 are each a hydroxy-protecting group; X is an activated carboxyl group) and the protecting group is removed to yield the compound of formula I. COPYRIGHT: (C)1991,JPO ...

MDP derivatives and conjugates having haematipoietic function stimulating activity, and compositions containing same

Pharmaceutical compositions containing Muramyl dipeptide derivatives and conjugates or Muramyl dipeptide derivatives and conjugates combined with nucleoside derivatives which induce hematopoietic stem cell stimulation and mobilization into the circulating blood system. Methods to induce hematopoietic stem stimulation and mobilization, as well as methods to decrease myelotoxic effects using these pharmaceutical compositions.

COMPOSITIONS FOR APPLICATION IN HUMAN THERAPEUTICS, CHARACTERIZED BY THE ASSOCIATION OF A MURAMIL-PEPTIDE TO A CYTOQUINE.

LA INVENCION SE REFIERE A UNA COMPOSICION QUE ASOCIA, PARA SU APLICACION EN TERAPIA HUMANA, AL MENOS UNA CITOQUINA NATURAL O RECOMBINANTE, PREFERENTEMENTE HUMANA, CON LA MENOS UN MURAMILPEPTIDO ELEGIDO ENTRE LOS QUE, CUANDO SON ADMINISTRADOS "IN VIVO" EN ASOCIACION CON UN INTERFERON, INDUCEN TAMBIEN LA PRODUCCION INCREMENTADA IN VIVO DE UN ANTAGONISTA IL-1 RA DEL RECEPTOR DE LA INTERLEUQUINA I Y, PREFERENTEMENTE, NO INDUCEN UN CRECIMIENTO DE LAS CITOQUINAS IL-1, TNF Y IL-8. SE PUEDE UTILIZAR PARA TERAPIAS ANTIVIRALES, ANTITUMORALES Y/O PARA FAVORECER UNA RECONSTITUCION DEL SISTEMA HEMATOPOIETICO, PARTICULARMENTE EN PERSONAS CUYO SISTEMA INMUNITARIO ES O SE HA VUELTO DEFICIENTE. THE INVENTION REFERS TO A COMPOSITION THAT ASSOCIATES, FOR ITS APPLICATION IN HUMAN THERAPY, AT LEAST A NATURAL OR RECOMBINING CYTOKIN, PREFERENTLY HUMAN, WITH THE LESS A MURAMILPEPTIDE ELECTED BETWEEN THOSE, WHEN THEY ARE ADMINISTERED "IN VIVO WITH A LIVE" , ALSO INDUCED THE INCREASED IN VIVO PRODUCTION OF AN IL-1 RA ANTAGONIST OF THE INTERLEUQUINE RECEIVER I AND, PREFERREDLY, DO NOT INDUCE A GROWTH OF THE IL-1, TNF AND IL-8 CYTOKINS. IT CAN BE USED FOR ANTIVIRAL, ANTITUMORAL THERAPIES AND / OR TO FAVOR A RECONSTITUTION OF THE HEMATOPOIETIC SYSTEM, PARTICULARLY IN PEOPLE WHOSE IMMUNE SYSTEM IS OR HAS BEEN BECOMED DEFICIENT.

VACCINE COMPOSITIONS CONDITIONED FOR THE VACCINATION OF IMMUNITARY NON-NATIVE SUBJECTS AGAINST A DETERMINED PATHOGENIC AGENT AND CONTAINING A HAPTENA WHICH INCLUDES A CHARACTERISTIC ANTIGENIC SITE OF SAID PATHOGENIC AGENT OR AN OLIGOMER OF THIS HAPTEN

PROCESS FOR SEPARATING FACTORS HAVING ACTIVATION PROPERTIES OF LYMPHOCITES FROM CUBIC POPULATION INCUBATION MEDIA, ESPECIALLY GRANULOCYTO-MACROPHAGIC LINE, BY ANTIGEN-ANTIBODY REACTION USING ANTIBODIES ANTIBODIES

L'INVENTION CONCERNE UN PROCEDE DE SEPARATION OU DE PURIFICATION D'UN FACTEUR LAF, AYANT DES PROPRIETES D'ACTIVATION DES LYMPHOCITES ET, LE CAS ECHEANT, DES PROPRIETES PYROGENES-ENDOGENES, A PARTIR D'UN MILIEU BIOLOGIQUE LIQUIDE LE CONTENANT A L'ETAT DISSOUS, OU D'ENRICHISSEMENT DE CE MILIEU EN CE FACTEUR LAF. CE PROCEDE EST CARACTERISE PAR LA MISE EN CONTACT DE CE MILIEU AVEC DES ANTICORPS ANTI-MDP, ET LA RECUPERATION SOIT DU FACTEUR LAF LUI-MEME, A PARTIR DU COMPLEXE FACTEUR LAF-ANTICORPS ANTI-MDP, SOIT DU MILIEU ALORS SUBSTANTIELLEMENT DEPOURVU DE CE FACTEUR.

ADJUVANT COMPOSITION OF HUMOR AND CELL-MEDIATED IMMUNITY WITHOUT RESPONSE TO SELF-ANTIGENIC DETERMINANTS.

Immunogical adjuvants for weak vaccine antigens - are (2)-acetamido-deoxy (D)-glucopyranosyl (D)-propionyl (L)-alanyl (D)-glutamic acid esters and (D)-isoglutamines

VACCINE WITH INCREASED IMMUNOGENICITY

NOVEL CONJUGATES OF OLIGO-MURAMYLPEPTIDES AND BIOLOGICAL COMPOSITIONS CONTAINING THEM FOR THE ACTIVATION OF MACROPHAGES

Compositions for application in human therapy, characterized by the association of a muramyl-peptide with a cytokine.

WATER-SOLUBLE IMMUNOLOGICAL ADJUVANTS, ESPECIALLY FOR VACCINES, OBTAINED FROM MICROBACTERIA AND OTHER MICRO-ORGANISMS

MITOGENOUS AGENTS, IN PARTICULAR FROM BACTERIAL PEPTIDOGLYCANES

Oil-free adjuvant compsns causing no hypersensitisation - contg N-acetyl-muramyl-L-alanyl-D-isoglutamine pref in aq soln

Novel oil-free adjuvant compsns. contain N-acetylmuramyl-L-alanyl-D-isoglutamine (I) as active principle together with a pharmaceutically acceptable vehicle, prefd. being sterile injectable aaq. solns. of (I). Also claimed are lyophilised (I) prepns. suitable for preparing such solns. (I) has high non-specific adjuvant activity in aq. soln. and in physiological lquids (unlike prior art non-specific adjuants), and also does not induce host sensitisation to (I) or other adjuvants prefd. from mycobacteria. Compared with the use of (I) in water-oil emulsions as in the parent patent, difficulties due to the non-metabolisable nature of the oil and harmfulness of emulsion stabilisers are avoided. The compsns. increase the effectiveness of bacterial or viral vaccines, and are esp. for increasing the immunity of human or animal hosts to bacterial or viral infections, tumour antigens, protozoal antigens etc. They are also useful for making sera contg. antibodies active towards these antigents.

ADJUSTING AGENTS IMMUNITY

L'invention est relative à de nouveaux agents adjuvants immunologiques et anti-infectieux solubles dans l'eau. Ces agents répondent à la formule générale : The invention relates to novel adjuvant immunological and anti-infective agents soluble in water. These agents respond to the general formula:

2- (2-ACETAMIDO-2-DEOXY-3 - O-D-GLUCOPYRANOSYL) - D-PROPIONYL-L-ALANYL-D-GLUTAMIC ACID DIAMIDE AND DRUGS CONTAINING IT

L'invention est relative à un nouvel agent soluble dans l'eau, efficace comme agent adjuvant immunologique. L'agent adjuvant est le diamide de l'acide 2-(2-acétamido-2 -déoxy- 3 -O-D-glucopyranosyl) - D-propionyl-L-alanyl-D-glutamique. Cet agent sert à préparer des compositions médicamenteuses adjuvantes, utilisées pour accroître l'efficacité des vaccins. The invention relates to a novel agent soluble in water, effective as an immunological adjuvant agent. The adjuvant is 2- (2-Acetamido-2-deoxy-3 -O-D-glucopyranosyl) - D-propionyl-L-alanyl-D-glutamic acid diamide. This agent is used in the preparation of adjuvant drug compositions, used to increase the effectiveness of vaccines.

NOVEL ESTER COMPOUNDS OF MURAMYL-PEPTIDE, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, IN PARTICULAR IN THE FORM OF LIPOSOMES

L'invention est relative à de nouveaux composés du type muramyl-peptide décrits dans la demande de brevet principal ainsi qu'à leur application. Selon l'invention, les composés de la famille en question, dont un membre particulièrement représentatif est le décylester de la N-acetyl-muramyl-L-alanyl- D-isoglutamine, sont préparés sous forme de liposomes. Les liposomes selon l'invention sont utiles notamment à titre de médicaments en raison des propriétés pharmacologiques particulières qu'ils présentent. The invention relates to new compounds of the muramyl-peptide type described in the main patent application as well as to their application. According to the invention, the compounds of the family in question, a particularly representative member of which is the decyl ester of N-acetyl-muramyl-L-alanyl-D-isoglutamine, are prepared in the form of liposomes. The liposomes according to the invention are useful in particular as medicaments because of the particular pharmacological properties that they exhibit.

IMMUNOMODULATOR COMPOSITIONS, BASED ON PRODUCTS COMPRISING AT LEAST ONE PHOSPHATE OR SULFATE GROUP, AND A GEL OF AN ALUMINUM COMPOUND.

Diesters of muramyl peptides in an oral form.

NOVEL MURAMYL-PEPTIDE COMPOUNDS AND MEDICAMENTS CONTAINING THEM

L'invention est relative à de nouveaux agents adjuvants immunologiques solubles dans l'eau. Ces agents répondent à une formule de type : The invention relates to novel water-soluble immunological adjuvants. These agents respond to a formula such as:

COMPOSITIONS BASED ON HYDROPHOBIC SUBSTANCES, SOLUBILIZABLE IN AQUEOUS SOLVENT, PROCESS FOR OBTAINING SAME, AND USES THEREOF IN PARTICULAR IN THE PHARMACEUTICAL FIELD.

Enhanced immunogenic vaccine

Vaccines, composed of antigens absorbed on alum or formulated in an alum-containing composition, have enhanced immunogenicity over existing vaccines. The vaccines of the invention are characterized by their combination with 2-120 νg per kg or 0.1-6 mg by dose, preferentially 6-60 νg per kg or 0.3-3 mg by dose of a hydrosoluble muramyl peptide.

COMPOSITIONS BASED ON HYDROPHOBIC SUBSTANCES, SOLUBILIZABLE IN AQUEOUS SOLVENT, PROCESS FOR OBTAINING SAME, AND USES THEREOF IN PARTICULAR IN THE PHARMACEUTICAL FIELD.

Water soluble agents effective as immunological adjuvants for stimulating in the host the immune response to various antigens and compositions, notably vaccines containing said water soluble agents

Water soluble agents effective as immunological adjuvants for stimulating in the host the immune response to various antigens, comprising an acyl-muramic acid group, wherein acyl means acetyl or glycolyl, and a short peptide chain linked to said acyl-muramic acid group, the first and second amino acids of said peptide chain being preferentially alanine and glutamic acid respectively.

OLIGOMERS OF MURAMYL-PEPTIDE COMPOUNDS AND DRUGS CONTAINING THEM

L'invention concerne de nouveaux produits du type muramyl-peptide. Les produits sont des oligomères solubles dans l'eau, exempts de motifs N-acétyl-glucosamine, et dont les éléments monomères comportent un groupe dérivé de l'acide muramique sur lequel est fixée une chaîne de type peptidique comportant au moins deux résidus aminoacyle, le premier étant choisi parmi : L-alanyle, L-arginyle, L-asparagyle, L-histidyle, L-hydroxypropyle, L-isoleucyle, L-leucyle, L-méthionyle, L-phénylalanyle, L-prolyle, L-séryle, L-thréonyle, L-tryptophanyle, L-valyle, et le second aminoacyle est D-glutamyle ou D-isoglutaminyle. Les produits selon l'invention sont utiles, en particulier pour leurs propriétés immunorégulatrices, pour la préparation de compositions pharmaceutiques. The invention relates to new products of the muramyl-peptide type. The products are water-soluble oligomers, free from N-acetyl-glucosamine units, and whose monomeric elements comprise a group derived from muramic acid to which is attached a peptide-type chain comprising at least two aminoacyl residues, the first being chosen from: L-alanyl, L-arginyl, L-asparagyl, L-histidyl, L-hydroxypropyl, L-isoleucyl, L-leucyl, L-methionyl, L-phenylalanyl, L-prolyl, L-seryl, L-threonyl, L-tryptophanyl, L-valyl, and the second aminoacyl is D-glutamyl or D-isoglutaminyl. The products according to the invention are useful, in particular for their immunoregulatory properties, for the preparation of pharmaceutical compositions.

LA 2- (2-ACETAMIDO-2-DEOXY-3-O-D-GLUCOPYRANOSYL) -D-PROPIONYL-L-SERYL-D-ISOGLUTAMINE AND MEDICINES CONTAINING IT

METHOD OF ANALOGUE FOR THE PREPARATION OF ESTERS OF N-ACETYL-MURAMYL-L-ALANYL-D-GLUTAMIC ACID AND OF N-ACETYL-MURAMYL-L-ALANYL-D-ISOGLUTAMINE

Water-soluble agents having mitogenic properties obtained from nocardia cells, and processes for the preparation thereof

The invention pertains to a mitrogenic agent and to a process for obtaining same. It comprises the steps of cultivating Nocardiae cells, collecting them, subjecting them to a treatment for rupturing the integrity of their walls, such as by lysis, discarding the solid residue and collecting the aqueous fraction, causing the peptidoglycane fragments contained in this aqueous fraction to be separated therefrom and recovering the remaining fraction containing the mitogenic agent.

NEW ESTERS OF N-ACETYL-MURAMYL-AMINOACYL-GLUTAMIC ACID OR SUBSTITUTION DERIVATIVES THEREOF WITH ANTI-INFECTIOUS PROPERTIES AND / OR IMMUNOLOGICAL ADJUVANTS

New esters of muramyl-peptide are disclosed. The compounds of the invention have the chemical structure of a muramyl-peptide, the peptidic chain enclosing at least two aminoacyl residues, the second residue being a glutaminyl residue. Said compounds are characterized by the presence, on the position 8 of the glutaminyl residue, of a hydrocarbonaceous chain enclosing at least four carbons. Said compounds are appropriate for use as immunoregulating substances in pharmaceutical compositions or as laboratory reactants.

Immunogenic synthetic peptides having an epitope which is characteristic of the hepatitis B virus surface antigen, and compositions containing them

L'INVENTION CONCERNE UN PEPTIDE IMMUNOGENE PORTEUR D'UN EPITOPE DE L'ANTIGENE DE SURFACE DU VIRUS DE L'HEPATITEB. IL CONTIENT AU PLUS 30RESIDUS AMINO-ACYLE ET EST CARACTERISE EN CE QU'IL CONTIENT LA SEQUENCE ASP-TYR-GLN-GLY-MET-LEU-PRO-VAL-X-PRO-LEU-ILE-PRO-GLY-SER-Y-THR-THR-SER-THR-GLY-Z-X, DANS LAQUELLE: X EST CYSTEYLE, AMINOBUTYRYLE, ALANYLE OU SERYLE; Y EST SERYLE OU THREONYLE, ET Z EST PROLYLE OU SERYLE.

COMPOSITION BASED ON METABOLISABLE VEGETABLE OIL AND WATER, USED IN PARTICULAR FOR THE CONSTITUTION OF ADJUSTING PREPARATIONS, SUCH ADJUSTING PREPARATIONS AND THEIR PROCESS FOR OBTAINING

SYNTHETIC MOLECULE CONTAINING A PLURALITY OF SEPARATE EPITOPES, PROCESS FOR OBTAINING SAME AND APPLICATION TO THE PRODUCTION OF POLYVACCINES

Conjugates of haptenes and muramyl-peptides, endowed with immunogenic activity and compositions containing them

The invention relates to an immunogenic principle containing a specific antigen determinant of a predetermined native antigen. This immunogenic principle is constituted by a conjugate between a hapten bearing said antigenic site and a muramyl-peptide, essentially in the absence of supporting macromolecules, this conjugate having an immunogenic effect not only against itself, but also with respect to the native antigen carrying said antigenic site.

DERIVATIVES AND CONJUGATES OF MDP HAVING STIMULATORY ACTIVITY OF HEMATOPOIETIC FUNCTION AND COMPOSITIONS CONTAINING THEM

IMMUNOLOGICAL ADJUVANT CONSTITUTED BY N-ACETYL-MURAMYL-L-ALANYL-D-ISOGLUTAMINE P-AMINO-PHENYL

L'invention est relative à un nouvel agent adjuvant immunologique soluble dans l'eau. L'agent adjuvant est le 2-(p-amino-phényl-2-acétamido-2-déoxy-3-0-D-glucopyranosyl)-D-propio-nyl-L-alanyl-D-isoglutamine qui, dans sa forme glucoside, répond à la formule : The invention relates to a novel water-soluble immunological adjuvant. The adjuvant is 2- (p-amino-phenyl-2-acetamido-2-deoxy-3-0-D-glucopyranosyl) -D-propio-nyl-L-alanyl-D-isoglutamine which in its form glucoside, responds to the formula:

VACCINE COMPOSITIONS CONDITIONED FOR THE VACCINATION OF IMMUNITARY NON-NATIVE SUBJECTS AGAINST A DETERMINED PATHOGENIC AGENT AND CONTAINING A HAPTENA WHICH INCLUDES A CHARACTERISTIC ANTIGENIC SITE OF SAID PATHOGENIC AGENT OR AN OLIGOMER OF THIS HAPTEN

L'INVENTION CONCERNE UNE COMPOSITION DE VACCIN CONTRE UN AGENT PATHOGENE DETERMINE, CONTENANT UN HAPTENE SYNTHETIQUE POSSEDANT LUI-MEME UN SITE ANTIGENIQUE CARACTERISTIQUE DUDIT AGENT PATHOGENE OU UN OLIGOMERE DE CET HAPTENE. ELLE EST CONDITIONNEE A UN DOSAGE D'HAPTENE PROPRE A REIMMUNISER UN SUJET IMMUNITAIREMENT NON NAIF CONTRE LEDIT AGENT PATHOGENE, EN ASSOCIATION AVEC UN VEHICULE PHYSIOLOGIQUEMENT ACCEPTABLE. THE INVENTION RELATES TO A COMPOSITION OF A VACCINE AGAINST A SPECIFIC PATHOGENIC AGENT, CONTAINING A SYNTHETIC HAPTENE ITSELF HAVING A CHARACTERISTIC ANTIGENIC SITE OF SAID PATHOGENIC AGENT OR AN OLIGOMER OF THIS HAPTEN. IT IS CONDITIONED ON A DOSAGE OF HAPTENE SUITABLE TO REIMMUNIZE A SUBJECT IMMUNITARILY NON-NATIVE AGAINST THIS PATHOGENIC AGENT, IN ASSOCIATION WITH A PHYSIOLOGICALLY ACCEPTABLE VEHICLE.

WATER-SOLUBLE AGENTS HAVING MITOGENOUS AND / OR IMMUNO-STIMULATING PROPERTIES, OBTAINED FROM NOCARDIA CELLS, AND THEIR PREPARATION METHODS

Method for manufacturing varieties of a glycerol derivative

The 3-O-[N-acetylmuramyl-D-isoglutaminyl]-1,2-di-O-palmitoyl-sn-glycerol derivative of formula I wherein the carbon atom marked with an asterisk * has the R or, respectively, the S configuration, possesses interesting pharmacological, in particular immunomodulating properties. It is particularly indicated for use as an immunomodulant, as an adjuvant in vaccines and as a suppressing agent for IgE formation in e.g. type I allergies and atopical dermatitises. It is obtained by deprotection of a corresponding compound having one or more hydroxy groups(s) in protected form.

Muramyl peptide substituted on a peptide nitrogen and medicaments containing the same

The invention relates to novel compounds of the muramyl-peptide type and to their uses. The muramyl-peptides according to the invention comprise at least two aminoacyl residues in the peptide chain, the second of these aminoacyl residues being D-glutamyl, and they are characterized in that the nitrogen of the first amino-acyl, and forming part of the pepetide linkage connecting the muramyl group to the peptide residue, is substituted by an alkyl group. These compounds are useful notably for the preparation of pharmaceutical compositions, in particular by reason of their regulatory properties on the immune responses of the organism.

New compounds associating peptidyl or aminoacyl residues to lipophilic groups and pharmaceutical compositions containing said new compounds

Compounds of formula in which - (NH-CHR-CO) and (NH-CHR'-CO) independently from each other are residues of aminoacids of the group containing glycine, alanine, β-alanine, arginine, asparagine, cysteine, glutamine, histidine, hydroxyproline, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophane and valine; - m is zero or 1, - n is 1 or 2, - p is 0.1.2 or 3 - Y is either H or an acyl group with up to 4 carbon atoms - R 1 and R 2 are the same or different, at least one of them being a lipophilic group comprising a hydrocarbon chain containing at least 10 carbon atoms; or a salt of said compound A preferred compound is '-O(L-alanyl-D-isoglutaminyl- These compounds are useful as anti-infectious agents.

DERIVATIVES OF MURAMYLDIPPTIDE.

The 3-O-[N-acetylmuramyl-D-isoglutaminyl]-1,2-di-O-palmitoyl-sn-glycerol derivative of formula I <CHEM> wherein the carbon atom marked with an asterisk * has the R or, respectively, the S configuration, possesses interesting pharmacological, in particular immunomodulating properties. It is particularly indicated for use as an immunomodulant, as an adjuvant in vaccines and as a suppressing agent for IgE formation in e.g. type I allergies and atopical dermatitises. It is obtained by deprotection of a corresponding compound having one or more hydroxy groups(s) in protected form.

DERIVATIVES AND CONJUGATES OF MDP THAT PRESENT A STIMULATING ACTIVITY OF THE HEMATOPOIETIC FUNCTION AND COMPOSITIONS THAT CONTAIN THEM

Mdp derivatives and conjugates having haematopoietic function stimulating activity, and compositions containing same

A pharmaceutical composition for stimulating the haematopoietic function and preventing the myelotoxic side-effects of some treatments, containing at least one water-soluble muramyl peptide derivative such as Muradimetide, muroctasine or MTP-PE.

Composition possessing immunoregulatory properties, in particular of non-specific immunological adjuvants, based on muramyl peptide and an aluminium derivative

The invention relates to a composition possessing adjuvant properties, reinforcing the immunoprotective activity of natural or synthetic immunogenic agents. It consists of a combination of an aluminium derivative itself having adjuvant properties, in particular aluminium hydroxide, and a muramyl peptide adjuvant, in particular N-acetylmuramyl-L-alanyl-D-glutamine alpha -n-butyl ester.

An peptide polymerisationsprodukte gebundene muramyl-peptide und sie enthaltende pharmazeutische zusammensetzungen.

Procede de separation ou de purification d'un facteur favorisant le sommeil a partir d'un milieu biologique par une reaction immunologique du type antigene-anticorps

L'INVENTION CONCERNE UN PROCEDE DE SEPARATION OU DE PURIFICATION D'UN FACTEUR FAVORISANT LE SOMMEIL (FACTEUR "S") A PARTIR D'UN MILIEU BIOLOGIQUE LE CONTENANT, TEL QUE L'URINE. CE PROCEDE EST CARACTERISE PAR LA MISE EN CONTACT DE CE MILIEU AVEC DES ANTICORPS ANTI-MDP ET PAR LA RECUPERATION, A PARTIR DU COMPLEXE FACTEUR "S"-ANTICORPS ANTI-MDP, DU FACTEUR "S" LUI-MEME.

Glycopeptides du type 2-(2-acetamido-2-desoxy-3-o-d-glucopyranosyl)-alcanoyl-aminoacyl-nor leucine ou derives de ces glycopeptides et compositions immunoadjuvantes les contenant

Glycopeptides du type 2-(2-acetamido-2-desoxy-3-o-d-glucopyranosyl)-alcanoyl-aminoacyl-nor leucine ou derives de ces glycopeptides et compositions immunoadjuvantes les contenant

L'INVENTION CONCERNE DES COMPOSES CHOISIS PARMI DES GLYCOPEPTIDES DU TYPE 2-(2-ACETAMIDO-2-DESOXY-3-O-D-GLUCOPYRANOSYL)- ALCANOYL-AMINOACYL-NOR LEUCINE SUR LESQUELS SONT, LE CAS ECHEANT, GREFFES PAR COUPLAGE COVALENT. CES COMPOSES, DOUES DE PROPRIETES IMMUNOADJUVANTES, PEUVENT ETRE UTILISES POUR LA CONSTITUTION DE COMPOSITIONS DE VACCINS.

Zusammensetzungen für die anwendung in menschlicher therapie, charakterisiert durch die assoziation eines muramylpeptids mit einem cytokin

Derivate und konjugete von mdp, eine von hämatopoitischer funktion stimulierende wirkung und deren enthaltende zusammensetzungen

Pasteurella haemolytica subunit vaccine containing capsular polysaccharide and muramyl dipeptide

Protection of ruminants against bacterial pneumonia caused by Pasteurella haemolytica has been achieved with a subunit vaccine. The vaccine contains two principle components: capsular polysaccharide of P. haemolytica and a synthetic adjuvant, muramyl dipeptide. This vaccine prevented bacterial infection of the lungs of vaccinated animals upon challenge with P. haemolytica. In contrast, animals that were not vaccinated or animals that were vaccinated with only capsular polysaccharide alone had severe lesions and high concentrations of P. haemolytica in the lungs.