Process of preparing stable prostaglandin E group-containing formulation

• US 4,092,428 A
• Filed: 03/07/1977
• Issued: 05/30/1978
• 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: Okazaki, Kiyoshi, Sekino, Jun, Shimizu, Hidemi, Murakami, Masuo, Kawata, Hiroitsu, Kawahara, Shigemi
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US05/774,680
• Time in Patent Office: 449 Days
• Field of Search: 424/305, 424/317
• US Class Current: 514/573
• 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 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-containing formulation which comprises adding to prostaglandin E₁, E₂ or E₃ at least one member selected from the group consisting of an arginine salt, a lysine salt and an alkali metal salt of deoxycholic acid and subjecting the resulting mixture to lyophilization, said arginine salt, lysine salt or alkali metal salt of deoxycholic acid being present in an amount varying between 1 to 200 mg. per 0.05 mg. of said prostaglandin E.

2. A process as claimed in claim 1 wherein said prostaglandin E 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.

3. A process as claimed in claim 1 wherein when said prostaglandin E is in a crystalline state, the crystals are dissolved in an organic solvent followed by removal of the solvent before the additive is added to said prostaglandin E.

4. A process as claimed in claim 3 wherein said organic solvent is ethanol or ethyl acetate.

5. A process as claimed in claim 1 wherein said prostaglandin E is a natural prostaglandin E.

6. A process as claimed in claim 1 wherein said prostaglandin E is a synthetic prostaglandin E.

7. A process according to claim 1 in which 5-100 mgs. of said arginine salt, lysine salt and alkali metal salts of deoxycholic acid are added to 0.05 mg. of said prostaglandin E.

8. A lyophilized pharmaceutical composition comprising as the active ingredient a therapeutically effective amount of prostaglandin E₁, E₂ or E₃ and at least one member selected from the group consisting of an arginine salt, a lysine salt and alkali metal salts of deoxycholic acid, said arginine salt, lysine salt and alkali metal salts of deoxycholic acid being present in an amount from 1 to 200 mg. per 0.05 mg. of said prostaglandin E.

9. A lyophilized pharmaceutical composition as claimed in claim 8 wherein said prostaglandin E 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.

10. A lyophilized pharmaceutical composition as claimed in claim 8 wherein said prostaglandin E is a natural prostaglandin E.

11. A lyophilized pharmaceutical composition as claimed in claim 8 wherein said prostaglandin E is a synthetic prostaglandin E.