26-04-2012 дата публикации
Номер: US20120101148A1
Автор:
Akin Aking,
William Querbes,
Frances M.P. Wong,
Joseph R. Dorkin,
Xiaojun Qin,
William Cantley,
Anna Borodovsky,
Soma De,
Muthiah Manoharan,
Muthusamy Jayaraman,
Kallanthottathil G. Rajeev,
AKING AKIN,
QUERBES WILLIAM,
WONG FRANCES M P,
DORKIN JOSEPH R,
QIN XIAOJUN,
CANTLEY WILLIAM,
BORODOVSKY ANNA,
DE SOMA,
MANOHARAN MUTHIAH,
JAYARAMAN MUTHUSAMY,
RAJEEV KALLANTHOTTATHIL G,
WONG FRANCES M.P.,
DORKIN JOSEPH R.,
RAJEEV KALLANTHOTTATHIL G.
The invention features an improved lipid formulation comprising a cationic lipid of formula (A), a neutral lipid, a sterol and a PEG or PEG-modified lipid, where Rand Rare independently alkyl, alkenyl or alkynyl, each can be optionally substituted, and Rand Rare independently lower alkyl or Rand Rcan be taken together to form an optionally substituted heterocyclic ring. In one embodiment, Rand Rare independently selected from oleoyl, pamitoyl, steroyl, linoleyl and Rand Rare methyl. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids. 2. The lipid formulation of claim 1 , wherein the neutral lipid is selected from DSPC claim 1 , DPPC claim 1 , DMPC claim 1 , DPPC claim 1 , POPC claim 1 , DOPE and SM.3. The lipd formulation of claim 1 , wherein the sterol is cholesterol.4. The lipid formulation of claim 1 , wherein the PEG lipid is PEG-Cto PEG-C claim 1 , PEG-Certo PEG-C claim 1 , or PEG-DSPE.5. The lipid formulation of claim 1 , wherein Rand Rof formula A are selected from selected from oleoyl claim 1 , pamitoyl claim 1 , steroyl claim 1 , linoleyl and Rand Rare methyl.6. The lipid formulation of claim 1 , wherein the cationic lipid of formula A is 2 claim 1 ,2-Dilinoleyl-4-dimethylaminoethyl-[1 claim 1 ,3]-dioxolane claim 1 , the neutral lipid is DSPC claim 1 , the sterol is cholesterol and the PEG lipid is PEG-DMG.7. The lipid formulation of comprising about 60% of cationic lipid of formula A claim 6 , about 7.5% of the neutral lipid claim 6 , about 31% of the sterol claim 6 , and about 1.5% of the PEG or PEG-modified lipid.8. The lipid formulation of claim 7 , wherein the formulation is prepared by an in-line mixing method.9. The lipid formulation of comprising about 57.5% of cationic lipid of formula A claim 6 , about 7.5% of the neutral lipid claim 6 , about 31.5% of the sterol claim 6 , and about 3.5% of the PEG or PEG-modified lipid.10. The lipid formulation of claim 9 , wherein the formulation is prepared by ...
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