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Summary for Patent: 6,193,998
|Title:||Method for producing liposomes with increased percent of compound encapsulated|
|Abstract:||The efficiency of encapsulating a drug into a liposomal formulation is increased by use of a lipid having a carbon chain containing from about 13 to about 28 carbons during preparation of the liposomes. Preferably the liposomes are multivesicular liposomes.|
|Inventor(s):||Ye; Qiang (San Diego, CA), Sankaram; Mantripragada Bhima (San Diego, CA)|
|Assignee:||SkyePharma Inc. (San Diego, CA)|
1. A method for producing a liposomal formulation comprising:
(a) forming a liposome, by any conventional means, containing at least one encapsulated compound and having at least one first amphipathic lipid having a carbon chain from about 1 to about 12 carbons in the lipid component of the formulation;
(b) determining the percent amount of encapsulated compound;
(c) substituting said at least one first amphipathic lipid having a carbon chain from about 1 to about 12 carbons in the lipid component of the formulation with at least one second amphipathic lipid with a substantially similar chemical structure, having from 1 to 16 more carbons in a fatty acyl chain of the second lipid;
wherein the increased number of carbons in the fatty acyl chain of the second lipid results in an increase in the percent of said at least one compound encapsulated in the formulation.
2. The method of claim 1 wherein the percent of the compound encapsulated is from about 7.5 to about 50 percent.
3. The method of clam 1 wherein the number of carbons is increased from 12 or less to a number in the range of from 13 to 28.
4. The method of claim 3 wherein the amphipathic lipid is a phospholipid.
5. The method of claim 3 wherein the amphipathic lipid is a saturated phospholipid.
6. The method of claim 3 wherein the percent of the compound encapsulated is increased to a value between about 30 and 85 percent.
7. The method of claim 4 wherein the phospholipid is selected from the group consisting of
8. The method of claim 1 wherein the fatty acyl chain in the first amphipathic lipid contains 14 carbons and the increase is by a minimum of 2 carbons.
9. The method of claim 1 wherein the fatty acyl chain in the first lipid contains 16 carbons and the increase is by a minimum of 2 carbons.
10. The method of claim 1 wherein the fatty acyl chain in the first lipid contains 18 carbons and the increase is by 2 carbons.
11. The method of claim 1 or 4 wherein the increase is by 4 carbons.
12. The method of claim 1 or 4 wherein the increase is by 6 carbons or more.
13. The method of claim 4 wherein the acyl chain is an SN.sub.1 or an SN.sub.2 chain, or both.
14. The method of claim 13 wherein the increase is in the SN.sub.1 chain.
15. The method of claim 13 wherein the increase is in the SN.sub.2 chain.
16. The method of claim 13 wherein the increase is in both the SN.sub.1 chain and the SN.sub.2 chain.
17. The method of claim 1 wherein steps (a) and (b) are performed only until the desired encapsulation efficiency is determined.
18. The method of claim 1 wherein only step (c) is performed once the desired formulation has been determined.
19. The method of claim 1 wherein 2 or more first amphipathic lipids having a carbon chain from about 1 to about 12 carbons in the lipid component of the formulation are substituted with second amphipathic lipids with substantially similar chemical structures, but having from 1 to 16 more carbons in the fatty acyl chains of the second lipid.
20. The method of claim 1 wherein 2 or more compounds are encapsulated.
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