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Chinese Patent Office

Generated: May 26, 2018

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Details for Patent: 6,770,290

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Title: Amphotericin B liposome preparation
Abstract:A novel composition and method for solubilizing amphiphilic drugs in a small amount of organic solvent for use in improved liposomes is disclosed. A phosphatidylglycerol is acidified in a small amount of organic solvent. The amphiphilic drug, such as Amphotericin B, suspended in organic solvent is then added to the acidified phosphatidylycerol and a soluble complex is formed between the phosphatidylglycerol and the amphiphilic drug. When the liposome composition incorporating the soluble complex is hydrated, the final pH of the hydrating aqueous buffer is carefully controlled. The Amphotericin B liposomes formed have markedly reduced toxicity.
Inventor(s): Proffitt; Richard T. (Arcadia, CA), Adler-Moore; Jill (Altadena, CA), Chiang; Su-Ming (Canoga Park, CA)
Assignee: Gilead Sciences, Inc. (Foster City, CA)
Filing Date:Oct 19, 1990
Application Number:07/600,154
Claims:1. A process for forming a soluble complex of an amphiphilic drug selected from the group consisting of polyene antibiotics, comprising forming a soluble complex of the amphiphilic drug and a phosphatidylglycerol in an acidified organic solvent having a pH of 1.0-3.0.

2. The process of claim 1 in which the phosphatidylglycerol is selected from the group consisting of distearoylphosphatidylglycerol, dilaurylphosphatidylglycerol, and dimyristoylphosphatidylglycerol.

3. The process of claim 1 in which the amphiphilic drug is amphotericin B.

4. The process of claim 2 in which the amphiphilic drug is amphotericin B.

5. The process of claim 3 in which the phosphatidylglycerol is distearoylphosphatidylglycerol.

6. A process for the formation of liposomes containing a polyene antibiotic, comprising forming a complex of a polyene antibiotic and a phosphatidylglylcerol in an acidified organic solvent having a pH of 1.0-3.0, removing the organic solvent to form a dried complex, and hydrating the dried complex with an aqueous medium to form liposomes having a diameter of less than 0.2 .mu.m.

7. The process of claim 6 in which the phosphatidylglycerol is selected from the group consisting of distearoylphosphatidylglycerol, dilaurylphosphatidylcglycerol, and dimyristoylphosphatidylglycerol.

8. The process of claim 6 in which a sterol is included with the complex during hydration to form liposomes containing a polyene antibiotic and a sterol.

9. The process of claim 7 in which a sterol is included with the complex during hydration to form liposomes containing a polyene antibiotic and a sterol.

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