Antifungal compositions

• US 5,952,300 A
• Filed: 03/28/1997
• Issued: 09/14/1999
• Est. Priority Date: 04/19/1996
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Nerurkar, Maneesh J., Kaufman, Michael J., Hunke, William A.
• Primary Examiner(s): Witz, Jean C.
• Assistant Examiner(s): HANLEY, SUSAN MARIE
• Application Number:
  US08/827,510
• Time in Patent Office: 900 Days
• Field of Search: 514/971, 514/970, 514/11, 514/9, 514/2, 424/489, 424/499, 530/317
• US Class Current: 514/3.3
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• 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

The invention is a pharmaceutical composition for intravenous administration to a patient comprising

a) a pharmaceutically effective amount of a compound having the formula ##STR1## and the pharmaceutically acceptable salts thereof; b) a pharmaceutically acceptable amount of an excipient such as a bulking agent effective to form a lyophilized cake; and

c) a pharmaceutically acceptable amount of acetate buffer effective to provide a pH of between about 4 and 7.

Claims

1. A pharmaceutical composition for intravenous administration to a patient comprising

a) a pharmaceutically effective amount of a compound having the formula ##STR9## and the pharmaceutically acceptable salts thereof, b) a pharmaceutically acceptable amount of an excipient effective to form a lyophilized cake;

and

c) a pharmaceutically acceptable amount of an acetate buffer effective to provide a pharmaceutically acceptable pH.

2. A pharmaceutical composition of claim 1 comprising

a) a pharmaceutically effective amount of Compound I;

b) between about 10-200 mg/ml of an excipient effective to form a lyophilized cake; and

c) a pharmaceutically acceptable amount of an acetate buffer effective to provide a pH of between about 4 and 7.

3. The composition of claim 2 comprising about 5-200 mg/ml of Compound I or a pharmaceutically acceptable salt thereof, about 12.5 mM to about 200 mM of an acetate buffer, about 10-200 mg/ml of bulking agent, and water.

4. The composition of claim 3 comprising about 30-50 mg/ml of Compound I or a pharmaceutically acceptable salt thereof, about 20-60 mM of an acetate buffer, about 30-70 mg/ml of bulking sugar or combination of bulking sugars effective to form a lyophilized cake, and water.

5. The composition of claim 4 comprising 42 mg/ml of Compound I or a pharmaceutically acceptable salt thereof, 25 mM of an acetate buffer, 30 mg/ml of sucrose, 20 mg/ml of mannitol, and water.

6. The composition of claim 4 comprising 42 mg/ml of Compound I or a pharmaceutically acceptable salt thereof, 50 mM of an acetate buffer, 30 mg/ml of sucrose, 20 mg/ml of mannitol, and water.

9. The composition of claim 2 wherein the excipient is a bulking agent or combination of bulking agents.

7. A process for making a pharmaceutical composition containing a compound having the formula ##STR10## and the pharmaceutically acceptable salts thereof, which comprises the steps of

a) dissolving a bulking agent or combination of agents in water;

b) adding acetic acid and adjusting the pH to about 3.7;

c) adding Compound I and adjusting the pH to about 5 with base;

d) filtering the solution thus prepared;

e) filling said solution into a lyophilization vial and freezing at -50°

C.; and

f) freeze drying the frozen solution.

8. A composition made by the process of claim 7.