Stable prostaglandin E group-containing formulation

• US 4,036,954 A
• Filed: 10/21/1974
• Issued: 07/19/1977
• Est. Priority Date: 11/02/1973
• Status: Expired due to Term

• Current Assignee: Yamanouchi Pharmaceutical Co., Ltd. (Astellas Pharma Incorporated)
• Original Assignee: Yamanouchi Pharmaceutical Co., Ltd. (Astellas Pharma Incorporated)
• Inventors: Murakami, Masuo, Okazaki, Kiyoshi, Sekino, Jun, Kawata, Hiroitsu, Shimizu, Hidemi, Kawahara, Shigemi
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US05/516,217
• Time in Patent Office: 1,002 Days
• Field of Search: 424/80, 424/175, 424/317, 424/318, 424/305, 424/176
• US Class Current: 514/573
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: C07C 405/00 Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof

Abstract

There is provided a process of preparing a prostaglandin E group-containing formulation by adding to a prostaglandin E group at least one additive selected from the group consisting of a thiol compound, a water soluble high molecular weight compound and a water-soluble salt of deoxycholic acid and then subjecting the mixture to lyophilization.

Claims

1. A process of preparing a stable prostaglandin E group-containing formulation which comprises adding to a prostaglandin E group compound an effective amount of at least one member selected from the group consisting of hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, water-soluble dextrin and dextran and subjecting the resulting mixture to lyophilization.

2. A process as claimed in claim 1 wherein said prostaglandin E group compound is prostaglandin E₁, prostaglandin E₂, or prostaglandin E₃.

3. A process as claimed in claim 1 wherein said prostaglandin E group compound is a member selected from the group consisting of 16-methyl-prostaglandin E₂, 3-methyl-prostaglandin E₂, 3,16(R)-dimethyl-prostaglandin E₂, 17-oxo-15-epi-prostaglandin E₂, and 16(R)-hydroxy-prostaglandin E₂.

4. A process as claimed in claim 1 wherein when said prostaglandin E group compound is in a crystalline state, the crystal is dissolved in an organic solvent followed by removing the solvent by vaporization before the additive is added to said prostaglandin E group compound.

5. A process as claimed in claim 4 wherein said organic solvent is ethanol or ethyl acetate.

6. A process as claimed in claim 1 wherein said prostaglandin E group compound is a natural prostaglandin E group compound.

7. A process according to claim 1 in which 5 - 250 mg. of said water-soluble dextrin and dextran is added per 0.05 mg. of said prostaglandin E group compound, and 0.1 - 150 mg. of said cellulose derivative is added to 0.05 mg. of said prostaglandin E group compound.

8. A lyophilized pharmaceutical composition comprising as the active ingredient a therapeutically effective amount of a PGE group compound and an effective amount of at least one member selected from the group consisting of hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, dextran and water soluble dextrin.

9. A lyophilized pharmaceutical composition according to claim 8 wherein said PGE group compound is PGE₂ and the additive is dextran.

10. A lyophilized pharmaceutical composition according to claim 8 in which 5 - 250 mg. of said water-soluble dextrin and dextran is added per 0.05 mg. of said prostaglandin E group compound, and 0.1 - 150 mg. of said cellulose derivative is added to 0.05 mg. of said prostaglandin E group compound.