Patent EA-004459-B1 (EA)
Title: Esters of l-carnitine or alkanoyl l-carnitines useful as cationic lipids for the intracellular delivery of pharmacologically active compounds
Inventor: PISANO CLAUDIO
IPC: A61K9/127
Filed: 2000-04-11
Abstract: 1. Compounds of formula (I) where n is an integer from 1 to 3; R is hydrogen or alkanoyl, straight or branched, with 2-6 carbon atoms; R1 and R2, which may be the same or different, represent a saturated or unsaturated straight acyl chain, with 3-20 carbon atoms; and X-is the anion of a pharmacologically acceptable acid. 2. A compound according to claim 1, in which R is selected from the group consisting of acetyl, propionyl, butyryl, valeryl and isovaleryl. 3. The compound according to claim 1, in which R1 and R2 are selected from the group consisting of hexanoyl, undecanoyl, myristoyl, palmitoyl or oleoyl. 4. The compound according to claim 1, in which X-is selected from the group consisting of chloride; bromide; iodide; aspartate; acid aspartate; citrate; acid citrate; tartrate; acid tartrate; phosphate; acid phosphate; fumarate; acid fumarate; glycerophosphate; glucose phosphate; lactate; maleate; acid maleate; mucate; orotate; oxalate; acid oxalate; sulphate; acid sulphate; trichloroacetate; trifluoroacetate; methane sulphonate; pamoate and acid pamoate. 5. Compound according to claim 1, selected from the group consisting of: -ester of L-carnitine bromide with 2-hydroxyacetyl-1,3-dipalmitoyl glycerin; -ester of acetyl L-carnitine bromide with 2-hydroxyacetyl-1,3-dipalmitoyl glycerol; -ester of propionyl L-carnitine bromide with 2-hydroxyacetyl-1,3-dipalmitoyl glycerol; -ester of isobutyryl L-carnitine bromide with 2-hydroxyacetyl-1,3-dipalmitoyl glycerol; -ester of isovaleryl L-carnitine bromide with 2-hydroxyacetyl-1,3-dipalmitoyl glycerol; -ester of L-carnitine bromide with 1,3-dihexanoyl-2-hydroxycetyl glycerol; -ester of acetyl L-carnitine bromide with 1,3-dihexanoyl-2-hydroxyacetyl glycerol; -ester of propionyl L-carnitine bromide with 1,3-dihexnoyl-2-hydroxyacetyl glycerol. 6. Use of a compound according to any of claims 1-5 for the preparation of liposomes. 7. Liposome comprising a compound of anyone of claims 1-5. 8. Liposome according to claim 7, further containing helper lipids. 9. Liposome according to claim 8, in which said helper lipid is selected from the group consisting of cholesterol, 1-palmitoyl-2-oleoyl phosphatidyl choline or dioleyl phosphatidyl choline. 10. Use of a liposome according to any one of claims 7-9, for the preparation of a composition useful for the transport of pharmacologically active compounds. 11. Use according to claim 10, in which the pharmacologically active compound is a naturally occurring or modified plasmid or polynucleotide. 12. Use according to claim 11, in which the plasmid or polynucleotide is useful in gene therapy. 13. Use according to claim 11, in which the plasmid or polynucleotide codes for a peptide or protein useful as a vaccine. 14. Use according to claim 10, in which the active compound is a drug. 15. Use according to claim 14, in which said drug is selected from the group consisting of anticancer, antiangiogenic, antiviral, antibacterial, antifungal, antiprotozoan agents, compounds active on the cardiovascular system, or immunogenic peptides. 16. Use according to claim 15, in which said drug is an anticancer or antiangiogenic agent. 17. Use according to claim 16, in which said anticancer agent is selected from the group consisting of taxol or a camptothecin derivative. 18. Use according to claim 17, in which said derivative of camptothecin is selected from the group consisting of -7-carbonitrilecamptothecin; -7-benzyloxyiminomethylcamptothecin, and -7-butoxyiminomethylcamptothecin. 19. Use of a liposome according to claims 7-9 for the preparation of a cosmetic composition. 20. Pharmaceutical composition comprising a liposome according to claims 7,8, or 9. 21. A composition according to claim 20, in which said liposome contains a pharmacologically active compound. 22. The composition according to claim 21, in which the active compound is a naturally occurring or modified plasmid or polynucleotide. 23. The composition according to claim 22, in which the plasmid or polynucleotide is useful in gene therapy. 24. The composition according to claim 22, in which the plasmid or polynucleotide codes for a peptide or protein useful as a vaccine. 25. A cosmetic composition comprising a liposome according to any of claims 7-9. 26. The composition according to claim 25, in which said liposome contains a substance with cosmetic activity. 27. The composition according to claim 21, in which said compound is selected from the group consisting of anticancer, antiangiogenic, antiviral, antibacterial, antifungal, antiprotozoan agents, compounds active on the cardiovascular system, or immunogenic peptides. 28. The composition according to claims 20-27, which can be administered orally, parenterally, intravenously, intramuscularly, subcutaneously, transdermally, or in the form of a nasal or mouth spray.