Sustained release compositions, process for producing the same and utilization thereof

• US 6,740,634 B1
• Filed: 07/06/2000
• Issued: 05/25/2004
• Est. Priority Date: 01/16/1998
• Status: Expired due to Fees

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Yamamoto, Kazumichi, Hata, Yoshio, Igari, Yasutaka, Saikawa, Akira
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): Lukton, David
• Application Number:
  US09/582,926
• Time in Patent Office: 1,419 Days
• Field of Search: 514/2, 530/399, 530/313, 424/468, 424/486
• US Class Current: 514/10.1
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: A61P 5/04 for decreasing, blocking or antagonising the activity of the hypothalamic hormones
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH

Abstract

A sustained-release composition containing a hydroxynaphthoic acid salt of a biologically active substance and a biodegradable polymer, a method of its production, and a pharmaceutical composition containing said sustained-release composition.

Claims

1. A sustained-release composition comprising a biologically active peptide, hydroxynaphthoic acid or salt thereof, and a biodegradable polymer or salt thereof.

2. A sustained-release composition according to claim 1 wherein the biologically active peptide is an LH-RH derivative.

3. A sustained-release composition according to claim 1 wherein the hydroxynaphthoic acid is 3-hydroxy-2-naphthoic acid.

4. A sustained-release composition according to claim 1 wherein the biodegradable polymer is an α

-hydroxycarboxylic acid polymer.

5. A sustained-release composition according to claim 4 wherein the α

-hydroxycarboxylic acid polymer is a lactic acid-glycolic acid polymer.

6. A sustained-release composition according to claim 5 wherein the content ratio of lactic acid and glycolic acid is 100/0 to 40/60 mol %.

7. A sustained-release composition according to claim 6 wherein the content ratio of lactic acid and glycolic acid is 100/0 mol %.

8. A sustained-release composition according to claim 5 wherein the weight-average molecular weight of the polymer is about 3,000 to about 100,000.

9. A sustained-release composition according to claim 8 wherein the weight-average molecular weight of the polymer is about 20,000 to about 50,000.

10. A sustained-release composition according to claim 2, wherein the LH-RH derivative is SEQ ID NO:

1.

11. A sustained-release composition according to claim 5, wherein the terminal carboxyl group content of the polymer is 50-90 micromol of the polymer.

12. A sustained-release composition according to claim 2, wherein the molar ratio of the hydroxynaphthoic acid or salt thereof and the LH-RH derivative or salt thereof is from 3 to 4 to 4 to 3.

13. A sustained-release composition according to claim 12, wherein the LH-RH derivative or salt thereof is contained at 14% (w/w) to 24% (w/w).

14. A sustained-release composition according to claim 1, wherein the biologically active peptide is very slightly soluble in water or soluble in water.

15. A sustained-release composition according to claim 1, which is intended for injection.

16. A method of treating prostatic cancer, prostatic hypertrophy, endometriosis, hysteromyoma, metrofibroma, precocious puberty, dysmenorrhea, or breast cancer, comprising administering a pharmaceutically effective amount of the sustained-release composition according to claim 10 to a mammal in need thereof.

18. A method of reducing fertility comprising administering a pharmaceutically effective amount of the sustained-release composition according to claim 10 to a mammal in need thereof.

17. A sustained-release composition comprising the hydroxynaphthoic acid salt of a biologically active peptide and a biodegradable polymer or salt thereof.