Pharmaceutical composition comprising polypeptide

Patent metadata

Field	Value
Publication number	US-9987368-B2
Application number	US-201615558893-A
Country	US
Kind code	B2
Filing date	Mar 16, 2016
Priority date	Mar 17, 2015
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

Found out is a pharmaceutical composition that sustained-releases a drug for a long term after administration into the body. Provided is a pharmaceutical composition comprising a drug and a polypeptide represented by Ac-(Arg-Ala-Asp-Ala) 4 -NH 2 , and further containing an organic solvent selected from the group consisting of polyethylene glycol, dimethyl sulfoxide, glycofurol, and N-methylpyrrolidone.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising:
a drug;
a polypeptide represented by Ac-(Arg-Ala-Asp-Ala) 4 -NH 2 ; and
an organic solvent, wherein:
the organic solvent is at least one organic solvent selected from the group consisting of polyethylene glycol, dimethyl sulfoxide, glycofurol, and N-methylpyrrolidone.

2. The pharmaceutical composition according to claim 1 , further comprising water.

3. The pharmaceutical composition according to claim 2 , wherein a volume ratio of the organic solvent to the water is 99:1 to 60:40.

4. The pharmaceutical composition according to claim 1 , wherein:
the organic solvent is polyethylene glycol, and
the polyethylene glycol has a mean molecular weight within a range of 90 to 2200.

5. The pharmaceutical composition according to claim 1 , wherein:
the organic solvent is polyethylene glycol, and
the polyethylene glycol is PEG 400.

6. The pharmaceutical composition according to claim 1 , wherein a content of the drug is 0.01 to 30% (w/v).

7. The pharmaceutical composition according to claim 1 , wherein a content of the polypeptide represented by Ac-(Arg-Ala-Asp-Ala) 4 -NH 2 is 0.001 to 5% (w/v).

8. The pharmaceutical composition according to claim 1 , wherein a content of the organic solvent is 70 to 99.99% (w/w).

9. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition consisting substantially only of the drug, the polypeptide represented by Ac-(Arg-Ala-Asp-Ala) 4 -NH 2 , the polyethylene glycol, and the water.

10. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition consisting substantially only of the drug, the polypeptide represented by Ac-(Arg-Ala-Asp-Ala) 4 -NH 2 , and the dimethyl sulfoxide.

11. The pharmaceutical composition according to claim 1 , wherein:
the drug is a compound or a salt thereof, the compound represented by formula (1):

wherein
R 1 represents a hydrogen atom, a halogen atom, a hydroxyl group, a C 1-6 alkyl group, a C 1-6 alkyl group substituted with one or more halogen atoms, a C 1-6 alkoxy group, or C 1-6 alkoxy group substituted with one or more halogen atoms; and
R 2 represents a hydrogen atom, C 1-6 alkyl group, a C 1-6 alkylcarbonyl group, or a C 1-6 alkylcarbonyl group substituted with one or more hydroxyl groups.

12. The pharmaceutical composition according to claim 1 , wherein the drug is 2-[[[2-[(hydroxyacetyl)amino]-4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide or a salt thereof.

13. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is for preventing or treating an eye disease.

14. The pharmaceutical composition according to claim 13 , wherein the pharmaceutical composition is for intravitreal or intracameral administration.

15. The pharmaceutical composition according to claim 13 , wherein the pharmaceutical composition is for sustained-releasing the drug.

16. A sustained-release ability imparting agent for drug comprising:
a polypeptide represented by Ac-(Arg-Ala-Asp-Ala) 4 -NH 2 ; and
an organic solvent, wherein
the organic solvent is at least one organic solvent selected from the group consisting of polyethylene glycol, dimethyl sulfoxide, glycofurol, and N-methylpyrrolidone.

17. A method of imparting a sustained-release ability to a drug, the method comprising adding a polypeptide represented by Ac-(Arg-Ala-Asp-Ala) 4 -NH 2 and an organic solvent to a drug, wherein:
the organic solvent is at least one organic solvent selected from the group consisting of polyethylene glycol, dimethyl sulfoxide, glycofurol, and N-methylpyrrolidone.

18. A method of preventing or treating an eye disease comprising administering the pharmaceutical composition according to claim 4 .

19. The sustained-release ability imparting agent according to claim 16 , further comprising water.

20. The method of imparting a sustained-release ability to a drug according to claim 17 , wherein: the organic solvent is polyethylene glycol, and the polyethylene glycol has a mean molecular weight within a range of 90 to 2200.

Assignees

• Santen Pharmaceutical Co Ltd

Inventors

• Miyazaki Tatsuya
• Masaki Kenji
• Okabe Komei
• Yamada Kazuhito

Classifications

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K47/20

  containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids · CPC title

• A61K47/42 Primary

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title