Reduction of liposome-induced adverse physiological reactions

• US 5,614,214 A
• Filed: 05/20/1994
• Issued: 03/25/1997
• Est. Priority Date: 05/21/1993
• Status: Expired due to Term

• Current Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Original Assignee: The Liposome Co., Inc. (Perrigo Company PLC)
• Inventors: Bhatia, Suresh K., Ahl, Patrick L., Janoff, Andrew S., Minchey, Sharma R.
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US08/247,053
• Time in Patent Office: 1,040 Days
• Field of Search: 424/450, 428/402.2, 436/829
• US Class Current: 424/450
• 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: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

Provided herein is a method of administering a liposome composition to an animal, the method involving adminstering to the animal a liposome composition containing an adverse physiological reaction-reducing effective amount of a liposome which has, in addition to a bioactive agent, a lipid bilayer containing a lipid and a surface agent-modified molecule. An adverse physiological reaction which may be experienced by the animal upon administration of a liposome composition is reduced by way of the presence of the surface agent-modified molecule in the liposome'"'"'s lipid bilayer.

Claims

1. A method reducing a blood pressure decrease associated with administration of a liposome to an animal which comprises incorporating a surface agent-modifying lipid which is a phosphatidylethanolamine conjugated to a dicarboxylic acid into a liposome such that the surface agent-modifying lipid comprises at least about 10 mole percent of the liposome'"'"'s bilayer and administering the liposome to the animal, wherein the liposome has an average diameter of from about 200 nm to about 5000 nm.

2. The method of claim 1, wherein the liposome (has a diameter of from about 200 nm to about 5000 nm) comprises a bioactive agent.

3. The method of claim 1, wherein the liposome has a diameter of from about 400 nm to about 5000 nm.

4. The method of claim 3, wherein the liposome has a diameter of from about 400 nm to about 1000 nm.

5. The method of claim 1, wherein the liposome is a large unilamellar liposome.

6. The method of claim 1, wherein the liposome is a multilamellar liposome.

7. The liposome of claim 6, wherein the multilamellar liposome comprises a solute entrapped in its aqueous compartments and wherein the concentration of the solute in each of the aqueous compartments is substantially equal.

8. The method of claim 1, wherein the dicarboxylic acid is succinic acid, glutaric acid, adipic acid, bimelic acid, suberic acid, tartaric acid, mucic acid, tetrafluorosuccinic acid or hexafluoroglutaric acid.

9. The method of claim 8, wherein the dicarboxylic acid is glutaric acid.

10. The method of claim 1, wherein the phosphatidylethanolamine has saturated acyl chains.

11. The method of claim 10, wherein the phosphatidylethanolamine is dipalmitoyl phosphatidylethanolamine (DPPE).

12. The method of claim 1, wherein the surface agent-modifying lipid further comprises a spacer group and wherein the spacer group comprises one or more organic functional groups capable of attaching to the glycerol backbone and the amino group of the phosphatidylethanolamine.

13. The method of claim 12, wherein the functional group is an hydroxyl, thiol, epoxide or amine group.

14. The method of claim 12, wherein the spacer group is ethylene glycol or polyethylene glycol.

15. The method of claim 2, wherein the bioactive agent is a contrast agent, antibacterial agent, antiviral agent, antifungal agent, anti-parasitic agent, tumoricidal agent, immunomodulator, vasodilator, radiolabel, radio-opaque compound, fluorescent compound, or anti-inflammatory agent.

16. The method of claim 15, wherein the bioactive agent is a water-soluble iodinated contrast agent selected from the group consisting of iohexol, iopamidol, ioxoglate, iotrolan, ioversol, iothalamate, iodimide, iodipamide,iopromide, metrizamide, iopentol, iodixanol, diatrizoate, iotroxic acid and mixtures and pharmaceutically acceptable salts thereof.

17. The method of claim 16, wherein the water-soluble iodinated contrast agent is iotralan.

18. The method of claim 1, wherein the liposome composition is administered by intravenous or intra-arterial administration.