Peptide copolymer compositions

• US 6,093,391 A
• Filed: 02/27/1998
• Issued: 07/25/2000
• Est. Priority Date: 10/08/1992
• Status: Expired due to Fees

• Current Assignee: Supratek Pharma, Inc.
• Original Assignee: Supratek Pharma, Inc.
• Inventors: Alakhov, Valery Y., Kabanov, Alexander V.
• Primary Examiner(s): Wortman, Donna C.
• Application Number:
  US09/031,279
• Time in Patent Office: 879 Days
• Field of Search: 424/85.1, 424/94.3, 424/182.1, 424/78.18, 424/78.31, 424/78.35, 514/3, 514/723, 514/727, 514/772.3
• US Class Current: 424/85.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/40 against enzymes

Abstract

Compositions of peptides and block copolymers and methods of treatment using the same. The compositions enhance the activity of peptide-based and related biological agents, and reduce adverse side effects.

Claims

1. A composition comprising a mixture of poly(oxyethylene)-poly(oxypropylene) (POE-POP) block copolymers and a protein, peptide or derivative thereof wherein the mixture comprises at least one block copolymer with ethylene(oxide) content of 50% or less, and at least one block copolymer with ethylene(oxide) content of 50% or more.

2. The composition according to claim 1, wherein at least one of the block copolymers is of the formula:

##STR9## in which x, y, z, i, and j have values from about 2 to about 400, and wherein for each R¹, R² pair, one is hydrogen and the other is a methyl group.

3. The composition according to claim 1 wherein at least one of the block copolymers is of the formula:

##STR10## wherein for each R¹, R² pair, one is hydrogen and the other is a methyl group.

4. The composition of claim 1 wherein at least one of the block copolymers has the formula:

##STR11## in which x, y, and z have values from about 2 to about 400.

5. The composition of claim 1 wherein the protein, peptide or derivative thereof is covalently modified with a hydrophobe.

6. The composition according to claim 5 wherein said hydrophobe is a lipid.

7. The composition according to claim 5 wherein said hydrophobe is a fatty acid residue.

8. The composition according to claim 1, wherein said protein, peptide or derivative thereof has a molecular weight of at least 1,000.

9. The composition according to claim 1, wherein said protein, peptide or derivative thereof has a molecular weight of at least 5,000.

10. The composition according to claim 1, wherein said protein, peptide or derivative thereof has a molecular weight of at least 10,000.

11. The composition according to claim 1, wherein the protein, peptide or derivative thereof is selected from the group consisting of immunomodulators, cytokines, hormones, enzymes, tissue plasminogen activators, clotting factors, colony stimulating factors, and erythropoetins.

12. The composition according to claim 11 wherein the hormone is a human growth hormone.

13. The composition according to claim 1 wherein the protein, peptide, or derivative thereof is a neuropeptide, or derivative thereof.

14. The composition according to claim 1 wherein the protein, peptide, or derivative thereof is selected from the group consisting of recombinant soluble receptors and monoclonal antibodies.

15. A method of treatment comprising administering to a patient a composition comprising a mixture of poly(oxyethylene)-poly(oxypropylene) block copolymers and a protein, peptide or derivative thereof, wherein the mixture comprises at least one block copolymer with ethylene(oxide) content of 50% or less, and at least one block copolymer with ethylene(oxide) content of 50% or more.

16. The method according to claim 15, wherein at least one of the block copolymers is of the formula:

##STR12## in which x, y, z, i, and j have values from about 2 to about 400, and wherein for each R¹, R² pair, one is hydrogen and the other is a methyl group.

17. The method according to claim 15 wherein at least one of the block copolymers is of the formula:

##STR13## wherein for each R¹, R² pair, one is hydrogen and the other is a methyl group, and the ethylene(oxide) content of said block copolymer is less than 50%.

18. The method of claim 15 wherein the protein, peptide or derivative thereof is covalently modified with a hydrophobe.

19. The method according to claim 18 wherein said hydrophobe is a lipid.

20. The method according to claim 18 wherein said hydrophobe is a fatty acid residue.

21. The method according to claim 15, wherein said protein, peptide or derivative thereof has a molecular weight of at least 1,000.

22. The method according to claim 15, wherein said protein, peptide or derivative thereof has a molecular weight of at least 5,000.

23. The method according to claim 15, wherein said protein, peptide or derivative thereof has a molecular weight of at least 10,000.

24. The method according to claim 15, wherein the protein, peptide or derivative thereof is selected from the group consisting of immunomodulators, cytokines, hormones, enzymes, tissue plasminogen activators, clotting factors, colony stimulating factors, and erythropoetins.

25. The method according to claim 24 wherein the hormone is a human growth hormone.

26. The method according to claim 15 wherein the protein, peptide, or derivative thereof is a neuropeptide, or derivative thereof.

27. The method according to claim 15 wherein the protein, peptide, or derivative thereof is selected from the group consisting of recombinant soluble receptors and monoclonal antibodies.