Formulated composition

• US 20030195142A1
• Filed: 05/06/2003
• Published: 10/16/2003
• Est. Priority Date: 04/08/1999
• Status: Active Grant

• Current Assignee: Douglas A. Yeung, James Q. Oeswein, John R. Smikahl, Sharon X. Wang
• Original Assignee: Douglas A. Yeung, James Q. Oeswein, John R. Smikahl, Sharon X. Wang
• Inventors: Oeswein, James Q., Wang, Sharon X., Yeung, Douglas A., Smikahl, John R.
• Granted Patent: US 7,186,686 B2
• Time in Patent Office: Days
• US Class Current: 514/6.5
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 530/808 Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products

Abstract

A composition is disclosed that comprises a mixture of polypeptides of opposite charge and an excipient selected from the group consisting of arginine, lysine, glutamic acid, sodium dodecyl sulfate, beta-hydroxy cyclodextrin, and beta-cyclodextrin sulfobutyl ether.

Claims

1. A composition comprising a mixture of pharmaceutically-active polypeptides of opposite charge and an excipient selected from the group consisting of arginine, lysine, glutamate, sodium dodecyl sulfate, and a combination of beta-hydroxy cyclodextrin and arginine, wherein the polypeptides are soluble in the composition.

2. The composition of claim 1 wherein the excipient is arginine.

3. The composition of claim 1 wherein two or more of said excipients are used.

4. The composition of claim 3 wherein the excipients are arginine, sodium dodecyl sulfate, and beta-cyclodextrin sulfobutyl ether and the polypeptides are IGF-I and an insulin that is not NPH-insulin.

5. The composition of claim 1 wherein the polypeptides are IGF-I and insulin.

6. The composition of claim 5 wherein the volume:

volume ratio of insulin;

IGF-I is from about 1;

15 to 15;

1.

7. The composition of claim 6 wherein the volume:

volume ratio of insulin;

IGF-I is from about 1;

6 to 6;

1.

8. The composition of claim 7 wherein the volume:

volume ratio of insulin;

IGF-I is from about 0.2;

1 to about 1;

1.

9. The composition of claim 1 further comprising a buffer.

10. The composition of claim 9 wherein the buffer is at a pH of about 7 to 7.5.

11. The composition of claim 10 wherein the buffer is histidine.

12. The composition of claim 1 further comprising phosphate-buffered saline.

13. The composition of claim 1 further comprising a stabilizer.

14. The composition of claim 5 wherein the excipient is arginine and additionally comprising histidine and a phenol.

15. The composition of claim 5 wherein the excipient is arginine in a concentration of about 100 to 300 mM and the ratio of insulin:

IGF-I is from about 0.1;

1 to 10;

1.

16. The composition of claim 15 further comprising beta-cyclodextrin sulfobutyl ether as excipient in a concentration of about 1-10%.

17. The composition of claim 5 wherein the excipient is sodium dodecyl sulfate in a concentration of about 1-10% and the ratio of insulin:

IGF-I is about 1;

1 to 6;

1.

18. The composition of claim 6 comprising about 5-20 mg/ml IGF-I, about 2-10 mg/ml insulin, about 100-200 mM arginine, about 5-20 mM histidine at pH about 7-7.5 and about 1-5 mg/ml phenol.

19. The composition of claim 7 comprising about 10 mg/ml IGF-I, about 3-4 mg/ml insulin, about 160 mM arginine, about 10 mM histidine at pH 7.2 and about 3 mg/ml phenol.

20. The composition of claim 1 wherein the polypeptides are not complexed.

21. A kit comprising:

(a) a container comprising the composition of claim 1 comprising effective amounts of the polypeptides; and

(b) instructions for using the above composition to treat a disorder against which the composition is effective.

22. The kit of claim 21 wherein the polypeptides are IGF-I and an insulin and the disorder is a hyperglycemic disorder.

23. A method for preparing the composition of claim 1 comprising mixing together as component (a) a first polypeptide in an excipient selected from the group consisting of arginine, lysine, glutamic acid, sodium dodecyl sulfate, beta-hydroxy cyclodextrin, and beta-cyclodextrin sulfobutyl ether;

and as component (b) a second polypeptide having an opposite charge from the first polypeptide.

24. The method of claim 23 further comprising incubating the mixture for a period of time at about 30-40°

C., wherein the composition further comprises phosphate-buffered saline.

25. The method of claim 24 wherein the mixture is incubated for about 15 minutes at 37°

C.

26. A kit for preparing the composition of claim 1 comprising:

(a) a container comprising a first polypeptide in an excipient selected from the group consisting of arginine, lysine, glutamic acid, sodium dodecyl sulfate, and a combination of beta-hydroxy cyclodextrin and arginine, and;

(b) a container comprising a second polypeptide having an opposite charge from the first polypeptide; and

(c) instructions for combining the contents of containers (a) and (b).

27. The kit of claim 26 wherein when the polypeptides are combined, the composition is a pharmaceutically acceptable formulation.

28. The kit of claim 27 wherein the pharmaceutically acceptable formulation is for treating a hyperglycemic disorder.

29. The kit of claim 26 wherein the first polypeptide is IGF-I and the second polypeptide is an insulin.

30. The kit of claim 26 wherein the excipient is arginine.

31. The kit of claim 30 wherein container (a) comprises about 5-20 mg/ml IGF-I, about 100-200 mM arginine, about 5-20 mM histidine at about pH 7-7.5 and about 1-5 mg/ml phenol.

32. The kit of claim 31 wherein container (a) comprises about 10 mg/ml IGF-I, about 160 mM arginine, about 10 mM histidine at about pH 7.2 and about 3 mg/ml phenol.