Liposomes useful for drug delivery

Patent metadata

Field	Value
Publication number	US-9724303-B2
Application number	US-201514965140-A
Country	US
Kind code	B2
Filing date	Dec 10, 2015
Priority date	May 3, 2004
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

The present invention provides liposome compositions containing substituted ammonium and/or polyanion, and optionally with a desired therapeutic or imaging entity. The present invention also provide methods of making the liposome compositions provided by the present invention.

First claim

The invention claimed is:

1. An irinotecan liposome composition comprising irinotecan sucrose octasulfate encapsulated in lipid vesicles comprising one or more phospholipids, encapsulating a total of 150-550 mg irinotecan base per mmol total vesicle phospholipids.

2. The irinotecan liposome composition of claim 1 , containing a total of 500 mg irinotecan base per mmol total vesicle phospholipids.

3. The irinotecan liposome composition of claim 1 , wherein the lipid vesicles consist of a lecithin, cholesterol, and an amphipathic polymer.

4. The irinotecan liposome composition of claim 3 , wherein the lecithin is a diacylphosphatidylcholine.

5. The irinotecan liposome composition of claim 3 , wherein the amphipathic polymer is a polyethylene glycol-lipid derivative.

6. The irinotecan liposome composition of claim 3 , wherein the amphipathic polymer comprises a polyethylene glycol-lipid derivative having a poly(ethylene glycol) portion with a molecular weight from about 250 to about 20,000.

7. The irinotecan liposome composition of claim 3 , wherein the amphipathic polymer is selected from the group consisting of a polyethylene glycol phosphatidylethanolamine, a polyethylene glycol-diacylglycerol, and a polyethyleneglycol-ceramide derivative.

8. The irinotecan liposome composition of claim 3 , wherein
a. the lecithin is DSPC and
b. the amphipathic polymer is a polyethylene glycol-lipid derivative having a poly(ethylene glycol) portion with a molecular weight from about 250 to about 20,000.

9. The irinotecan liposome composition of claim 1 , wherein the lipid vesicles comprise an uncharged lipid component and a neutral phospholipid.

10. The irinotecan liposome composition of claim 9 , wherein the lipid vesicles comprise one or more uncharged lipid component(s) selected from the group consisting of: cholesterol, ceramide, diacylglycerol, an acyl(poly ether) and an alkylpoly(ether).

11. The irinotecan liposome composition of claim 9 , wherein the lipid vesicles comprise a neutral phospholipid selected from the group consisting of: a diacylphosphatidylcholine, a sphingomyelin, and a diacylphosphatidylethanolamine.

12. The irinotecan liposome composition of claim 11 , wherein the lipid vesicles comprise a neutral phospholipid selected from the group consisting of: a diacylphosphatidylcholine, a sphingomyelin, and a diacylphosphatidylethanolamine.

13. An irinotecan liposome dispersion comprising irinotecan liposomes encapsulating irinotecan sucrose octasulfate in unilamellar lipid bilayer vesicles having a size of about 110 nm and comprising one or more phospholipids, the irinotecan liposomes encapsulating a total of 150-500 mg irinotecan free base per mmol total vesicle phospholipids.

14. The irinotecan liposome dispersion of claim 13 , wherein the vesicles comprise a lecithin, cholesterol and a polyethylene glycol-lipid derivative.

15. The irinotecan liposome dispersion of claim 14 , wherein the vesicles consist of a lecithin, cholesterol and a polyethylene glycol-lipid derivative.

16. The irinotecan liposome dispersion of claim 14 , wherein the vesicles consist of DSPC, cholesterol and a polyethylene glycol-lipid derivative.

17. The irinotecan liposome dispersion of claim 14 , wherein the vesicles consist of DSPC, cholesterol and N-(methoxy-poly(ethylene glycol)-oxycarbonyl)-distearoylphosphatidylethanolamine (PEG-DSPE).

18. The irinotecan liposome dispersion of claim 14 , wherein the irinotecan liposomes encapsulate a total of 500 mg irinotecan free base as irinotecan sucrose octasulfate.

19. The irinotecan liposome dispersion of claim 18 , having a total irinotecan free base concentration of 3.44 to 4.62 mg/mL of the irinotecan liposome dispersion.

20. An irinotecan liposome dispersion comprising irinotecan liposomes encapsulating irinotecan sucrose octasulfate in unilamellar lipid bilayer vesicles having a size of about 110 nm and consisting of DSPC, cholesterol and a polyethylene glycol-lipid derivative, the irinotecan liposomes encapsulating a total of 150-500 mg irinotecan free base as irinotecan octasulfate per mmol total vesicle phospholipids, and up to 5 mg irinotecan free base per mL of the liposome dispersion.

Assignees

• Ipsen Biopharm Ltd

Inventors

• Hong Keelung
• Drummond Daryl C
• Kirpotin Dmitri

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title