Claims
- 1. A device for the sustained release in vivo of a water soluble, biologically active agent wherein said agent is susceptible to aggregation, comprising:
a) a drug delivery device; and b) aggregation-stabilized, biologically active agent wherein said aggregation-stabilized agent is disposed within the drug delivery device.
- 2. A sustained release device of claim 1 wherein the drug delivery device is a biocompatible polymeric matrix.
- 3. A sustained release device of claim 1 wherein the aggregation-stabilized, biologically active agent includes a biologically active agent and an aggregation-stabilizer.
- 4. A sustained release device of claim 3 wherein the aggregation-stabilizer is at least one salting-out salt.
- 5. A sustained release device of claim 3 wherein the aggregation-stabilizer is a metal cation component.
- 6. A sustained release device of claim 5 wherein the aggregation-stabilizer and a metal cation of the metal cation component are complexed.
- 7. A sustained release device of claim 3 wherein the aggregation-stabilizer is a buffer.
- 8. A sustained release device of claim 3 wherein the aggregation-stabilizer is polyethylene glycol.
- 9. A sustained release device of claim 3 wherein the aggregation-stabilized, biologically active agent is in particulate form.
- 10. A composition for the sustained release in vivo of a water soluble, biologically active agent wherein said agent is susceptible to aggregation, comprising:
a) a biocompatible polymer; and b) aggregation-stabilized, biologically active agent wherein said aggregation-stabilized agent is disposed within the polymer.
- 11. A sustained release composition of claim 10 wherein the aggregation-stabilized, biologically active agent includes a biologically active agent and an aggregation-stabilizer.
- 12. A sustained release composition of claim 10 wherein the biologically active agent and the aggregation-stabilizer are mixed.
- 13. A sustained release composition of claim 10 wherein the aggregation-stabilizer reduces the solubility of the protein in an aqueous fluid.
- 14. A composition of claim 13 wherein the anti-aggregation agent is a salting-out salt.
- 15. A composition of claim 14 wherein the salting-out salt comprises a salt containing a cation selected from the group consisting Mg+2, Li+, Na+, K+, NH4+ and combinations thereof.
- 16. A composition of claim 13 wherein the salting-out salt comprises a salt containing an anion selected from the group consisting of SO4−2, HPO4−2, acetate, citrate, tartrate, CL−, NO3−, CLO3−, I−, CLO4−, SCN− and combinations thereof.
- 17. A composition of claim 13 wherein the salting-out salt is ammonium sulfate.
- 18. A composition of claim 11 wherein the aggregation stabilizer is mannitol.
- 19. A sustained release composition of claim 11 wherein the aggregation-stabilizer is a buffer.
- 20. A sustained release composition of claim 11 wherein the aggregation-stabilizer is a metal cation from a metal cation component.
- 21. A sustained release composition of claim 11 wherein the metal cation of said metal cation component is a biocompatible multivalent cation.
- 22. A sustained release composition of claim 12 wherein the multivalent metal cation is selected from the group consisting of Zn+2, Ca+2, Cu+2, Mg+2 and combinations thereof.
- 23. A sustained release composition of claim 10 wherein the biocompatible polymeric matrix is formed of a biodegradable polymer.
- 24. A sustained release composition of claim 20 further comprising a second metal cation component, wherein the second metal cation component is dispersed within the biocompatible polymeric matrix.
- 25. A sustained release composition of claim 24 wherein the second metal cation component is selected from the group consisting of magnesium hydroxide, magnesium carbonate, calcium carbonate, zinc carbonate, magnesium acetate, zinc acetate, magnesium sulfate, zinc sulfate, magnesium chloride, zinc chloride, zinc citrate, magnesium citrate and a combination thereof.
- 26. A composition for the sustained release in vivo of a water soluble, biologically active agent aggregation, comprising:
a) a biodegradable polymer; and b) aggregation-stabilized, biologically active agent wherein said aggregation-stabilized agent is disposed within the biodegradable polymer.
- 27. A sustained release composition of claim 26 wherein the biodegradable polymer is poly(lactide-co-glycolide).
RELATED APPLICATIONS
[0001] This application is a Continuation of co-pending U.S. patent application Ser. No. 08/934,830, filed Sep. 22, 1997, which is a Continuation of U.S. patent application Ser. No. 08/521,744, filed Aug. 31, 1995, now abandoned, which is a Continuation-in-Part of U.S. patent application Ser. No. 08/765,558, which is the U.S. National Stage of International Application No.: PCT/US95/07348 filed Jun. 7, 1995, published in English, which is a Continuation-in-Part of U.S. application Ser. No. 08/279,784 filed Jul. 25, 1994, now U.S. Pat. No. 5,711,968. This application is also a Continuation-in-Part of U.S. patent application Ser. No. 08/478,502, filed Jun. 7, 1995, now U.S. Pat. No. 5,716,644 which is a Continuation-in-Part of U.S. patent application Ser. No. 07/885,307, filed Jun. 11, 1992, now abandoned; U.S. patent application Ser. No. 08/483,318, filed Jun. 7, 1995, now U.S. Pat. No. 5,674,534, which is a Continuation-in-Part of U.S. patent application Ser. No. 07/885,307, filed Jun. 11, 1992, now abandoned; U.S. patent application Ser. No. 08/473,544 filed Jun. 7, 1995, now U.S. Pat. No. 5,654,010, which is a Continuation-in-Part of U.S. patent application Ser. No. 07/984,323, filed Dec. 2, 1992, now abandoned; and U.S. patent application Ser. No. 08/477,725, filed Jun. 7, 1995, now U.S. Pat. No. 5,667,808, which is a Continuation-in-Part of U.S. application Ser. No. 07/984,323, filed Dec. 2, 1992, now abandoned. The entire teachings of the above application(s) are incorporated herein by reference.
Continuations (2)
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Sep 1997 |
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10278739 |
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08521744 |
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Continuation in Parts (9)
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08279784 |
Jul 1994 |
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08521744 |
Aug 1995 |
US |
Parent |
08478502 |
Jun 1995 |
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Child |
10278739 |
Oct 2002 |
US |
Parent |
07885307 |
Jun 1992 |
US |
Child |
08478502 |
Jun 1995 |
US |
Parent |
08483318 |
Jun 1995 |
US |
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10278739 |
Oct 2002 |
US |
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07885307 |
Jun 1992 |
US |
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08483318 |
Jun 1995 |
US |
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08473544 |
Jun 1995 |
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10278739 |
Oct 2002 |
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07984323 |
Dec 1992 |
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08473544 |
Jun 1995 |
US |
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08477725 |
Jun 1995 |
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Child |
10278739 |
Oct 2002 |
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07984323 |
Dec 1992 |
US |
Child |
08477725 |
Jun 1995 |
US |