Preparation of liposome and lipid complex compositions

• US 5,567,434 A
• Filed: 06/07/1995
• Issued: 10/22/1996
• Est. Priority Date: 03/31/1989
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Szoka, Francis C. Jr.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/480,227
• Time in Patent Office: 503 Days
• Field of Search: 424/1.21, 424/450, 424/484, 264/4.1, 264/4.3, 264/4.6, 264/4.7, 436/829
• US Class Current: 424/450
• CPC Class Codes: A61K 47/544 Phospholipids
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: Y10S 436/829 Liposomes, e.g. encapsulation

Abstract

Liposome and lipidic particle formulations of compounds are prepared by dissolving in a solution of liposome-forming lipids in an aprotic solvent such as DMSO, optionally containing a lipid-solubilizing amount of a lower alkanol, and either injecting the resulting solution into an aqueous solution, or the aqueous solution into the resulting solution. The resulting liposome or lipidic particle suspension may then be dialyzed or otherwise concentrated. This method is particularly useful for compounds which are poorly-soluble in aqueous solution, but is generally useful for any compound or combination of compounds which can be dissolved in the aprotic solvent or aprotic solvent/lower alkanol mixture.

Claims

1. A product of the process for preparing a lipid suspension of particle size less than about 10,000 nm in diameter encapsulating a therapeutically, pharmaceutically or diagnostically useful compound, which process comprises:

dissolving said useful compound and an encapsulating amount of a suitable lipid in a sufficient amount of a solvent mixture comprising a non-halogenated hydrocarbon aprotic solvent to provide a compound/lipid solution; and

extruding said compound/lipid solution through a suitably-sized aperture into an aqueous solution to form a lipid-compound suspension of particle size less than about 10,000 nm in diameter.

2. The product-by-process of claim 1 further comprising a lipid suspension of liposomes and a useful compound selected from the group consisting of cisplatin, doxorubicin, epinephrine, mebendazole, niridazole, and taxol.

3. The product-by-process of claim 1 further comprising a lipid suspension of lipidic particles and a useful compound selected from the group consisting of amphotericin B, nystatin, and primaricin.

4. The product-by-process of claim 1 wherein the lipid-compound suspension has a particle size between 20 and 600 μ

m and wherein the therapeutically, pharmaceutically, or diagnostically useful compound is amphotericin B.