Amphotericin B/cholesterol sulfate composition and method

• US 5,194,266 A
• Filed: 12/19/1991
• Issued: 03/16/1993
• Est. Priority Date: 08/08/1989
• Status: Expired due to Term

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Liposome Technology, Inc.
• Inventors: Guo, Luke S. S., Abra, Robert
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US07/812,075
• Time in Patent Office: 453 Days
• Field of Search: 424/450, 424/417, 514/31, 536/6.5, 536/16.8
• US Class Current: 424/450
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00

Abstract

An amphotericin B composition containing particles of amphotericin B and cholesterol sulfate, in a molar ratio of between about 1:1 to 2:1. The particles, when stored in lyophilized form and reconstituted in an aqueous suspension, have particle sizes predominantly between about 50-250 nm. The composition has stable particle sizes in an aqueous suspension over a several-day storage period. The composition is significantly less toxic and more effective in treating fungal infection than prior amphotericin B formulations.

Claims

1. An amphotericin B composition comprising particles of amphotericin B containing cholesterol sulfate in a mole ratio of amphotericin B to cholesterol sulfate of between about 1:

1 to 2;

1.

2. The composition of claim 1, wherein the particles are suspended in an aqueous medium, and have particle sizes predominantly between about 50-250 nm.

3. The composition of claim 2, which is produced by the steps of:

(a) dispersing an aqueous suspension of amphotericin B and cholesterol sulfate, in a molar ratio of between 1;

1 to 2;

1 to optical clarity,

(b) lyophilizing the suspension in the presence of a cryoprotectant, and

(c) reconstituting the lyophilized material with an aqueous medium.

4. The composition of claim 1, wherein the molar ratio of amphotericin B to cholesterol sulfate is about 1.5:

1 to 2;

1.