Claims
- 1. A process for preparing an insulin analog-protamine crystal, which comprises:
- combining an aqueous solution of human insulin wherein Pro at position B28 is substituted with Asp, and Lys at position B29 is substituted with Lys or Pro in a hexamer association state, and a protamine solution at a temperature from about 5.degree. C. to about 22.degree. C.;
- said aqueous solution comprising from about 0.35 to about 0.9% zinc by weight, human insulin wherein Pro at position B28 is substituted with Asp, and Lys at position B29 is substituted with Lys or Pro, and a phenolic derivative at a pH of about 7.1 to about 7.6;
- said protamine solution comprising protamine at a pH of about 7.1 to about 7.6 such that the final concentration of protamine is about 0.27 to about 0.35 mg protamine to 100 IU of insulin analog.
- 2. The process of claim 1, wherein the process is carried out at a temperature from about 8.degree. C. to about 22.degree. C.
- 3. The process of claim 2, wherein the process is carried out at a temperature from about 13.degree. C. to about 17.degree. C.
- 4. The process of claim 3, wherein the process is carried out in less than about 4 mg/mL sodium chloride.
- 5. The process of claim 4, wherein the insulin is AspB28-human insulin.
- 6. The process of claim 5, wherein the phenotic derivative is phenol or m-cresol.
- 7. The process of claim 6, wherein the phenolic derivative is phenol.
Parent Case Info
This application is a division of application Ser. No. 08/260,633 filed Jun. 16, 1994 now U.S. Pat. No. 5,461,031.
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Divisions (1)
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Number |
Date |
Country |
Parent |
260633 |
Jun 1994 |
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