Methods and compositions using liposome-encapsulated non-steroidal anti-inflammatory drugs

• US 6,759,057 B1
• Filed: 03/13/1989
• Issued: 07/06/2004
• Est. Priority Date: 06/12/1986
• Status: Active Grant

• Current Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Original Assignee: The Liposome Co., Inc. (Perrigo Company PLC), University of British Columbia
• Inventors: Weiner, Alan L., Cullis, Pieter R.
• Primary Examiner(s): Wang, Andrew
• Assistant Examiner(s): Tran, My Chau T
• Application Number:
  US07/323,182
• Time in Patent Office: 5,594 Days
• Field of Search: 424/450, 424/812, 264/4.6, 264/4.3, 264/4.1, 428/402.2
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: Y10S 424/812 Liposome comprising an antibody, antibody fragment, antigen, or other specific or nonspecific immunoeffector

Abstract

Methods and compositions are described for the treatment of inflammatory diseases including the use of liposomes to deliver non-steroidal anti-inflammatory drugs. Drugs may be encapsulated in the liposomes during their preparation, or alternatively, are combined with the liposomes following their formation. The composition may include glycolipids such as galactolipids including digalactosyl diglyceride, and the liposomes may be made by a number of procedures. The compositions may be administered to mammals including humans.

Claims

1. A composition comprising a liposome which comprises:

(i) a lipid consisting essentially of a glycolipid; and

,

(ii) a non-steroidal anti-inflammatory drug.

2. The composition of claim 1, wherein the liposome is a stable plurilamellar liposome.

3. The composition of claim 1, wherein the glycolipid is a glycosphingolipid or a galactolipid.

4. The composition of claim 3, wherein the glycolipid is a galactolipid.

5. The composition of claim 4, wherein the galactolipid is monogalactosyl diglyceride or digalactosyldiglyceride.

6. The composition of claim 5, wherein the galactolipid is digalactosyl diglyceride.

7. The composition of claim 1, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of acemetacin, alclofenac, azapropazone, benoxaprofen, benrilate, carprofen, cholinemagnesium trisalicylate, diclofenac, diflunisal, etodolac, fenbufen, fenclofenac, fenoprofen, fentiazac, feprazone, flufenamino acid, fluribiprofen, glucametacin, ibuprofen, indomethacin, indoprofen, isoxicam, ketoprofen, magnesium salicylic acid, meclofenamic acid, mefenamino acid, methylsalicylate, naproxen, niflumic acid, osmosin, oxaprozin, oxyphenbutazone, phenylbutazone, piroxicam, pirprofen, salicylamide, salicylic acid, salicylic acid acetate, salicylsalicylic acid, sodium salicylate, sulindac, suprofen, tenoxicam, tiaprofenic acid, tolmetin and zomepirac.

8. The composition of claim 7, wherein the drug is ibuprofen.

9. The composition of claim 7, wherein the drug is indomethacin.

10. The composition of claim 7, wherein the drug is naproxen.

11. The composition of claim 7, wherein the drug is piroxicam.

12. The composition of claim 7, wherein the drug is salicylic acid acetate.

13. The composition of claim 1, comprising a pharmaceutically acceptable carrier.

14. The composition of claim 13, wherein the carrier is adapted for oral administration.

15. A method of treating a mammal for inflammation, pain or fever comprising administering to the mammal an amount of the composition of claim 13 which comprises a therapeutically effective amount of the nonsteroidal anti-inflammatory drug.

16. A pharmaceutical composition comprising:

(a) a pharmaceutically acceptable carrier; and

,

(b) a liposome which comprises;

(i) a lipid component comprising a glycolipid; and

,

(ii) a non-steroidal anti-inflammatory drug.