Concentrated aqueous solutions of argatroban

• US 5,679,690 A
• Filed: 02/02/1995
• Issued: 10/21/1997
• Est. Priority Date: 02/03/1994
• Status: Expired due to Term

• Current Assignee: Mitsubishi Pharma Corporation (Mitsubishi Chemical Group Corp.)
• Original Assignee: Synthelabo (Paris Cedex, FR) (Sanofi )
• Inventors: Avril, Veronique, Andre, Frederic, Montel, Jean
• Primary Examiner(s): Dentz, Bernard
• Assistant Examiner(s): DAHLEN, GARTH
• Application Number:
  US08/382,791
• Time in Patent Office: 992 Days
• Field of Search: 514/314, 546/166, 552/550
• US Class Current: 514/314
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• 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: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

Concentrated aqueous solutions of argatroban containing argatroban, a micelle-forming agent and a lipoid substance.

Claims

1. A concentrated aqueous solution of argatroban, which comprises argatroban, one or more micelle-forming agents and one or more lipoid substances, wherein the micelle-forming agent is a cholic acid derivative of general formula:

##STR2## in which each of R₁, R₂ and R₃ independently represents a hydrogen atom, hydroxy group or keto exocyclic group, and R₄ represents a carboxy group or a carboxy group bonded by an amide linkage to the amino group of an amino acid.

2. A solution according to claim 1 wherein the derivative of general formula (I) contains one or two double bonds in the steroid skeleton.

3. A solution according to claim 1, wherein the derivative of general formula (I) is in the form of an alkali metal salt.

4. A solution according to claim 1, wherein the lipoid substance is a phosphatide.

5. A solution according to claim 4, wherein the phosphatide is a phosphatidylcholine.

6. A solution according to claim 1, which contains one or more excipients as usually used in the preparation of liquid pharmaceutical forms or of dried pharmaceutical forms which lead after reconstitution to liquid forms.

7. A solution according to claim 1, wherein the molar ratio between the lipoid substance and the micelle-forming agent is from 0.1/1 to 2/1.

8. A solution according to claim 1, wherein the concentration of micelle-forming agent is from 0.01 to 0.5M.

9. A solution according to claim 1, wherein the argatroban concentration is from 1 mg/ml to 21 mg/ml.

10. A solution prepared at the time of use by dissolving a solid material obtained by atomization or lyophilization of all or part of the components of a solution according to claim 1.