Claims
- 1. A method for producing a sustained-release preparation of a growth hormone comprising the steps of:a) adding a volatile salt to an aqueous solution of a growth hormone to form a product solution; b) lyophilizing said product solution of step a) to form a powder comprising particles; c) dispersing said powder of step b) into an organic solvent solution of a biodegradable polymer to form a dispersion; and d) removing said organic solvent from said dispersion of step c) to obtain a sustained release preparation of a growth hormone.
- 2. The method according to claim 1, wherein the average particle size of said particles of step b) is not more than 10 μm in diameter.
- 3. The method according to claim 1, wherein said growth hormone is human growth hormone.
- 4. The method according to claim 1 further comprising adding an alcohol to said aqueous solution of said growth hormone in step a).
- 5. The method according to claim 4, wherein the alcohol is methanol or ethanol.
- 6. The method according to claim 4, wherein the alcohol is ethanol.
- 7. The method according to claim 1, wherein the volatile salt is an ammonium salt.
- 8. The method according to claim 7, wherein the ammonium salt is ammonium acetate, ammonium bicarbonate or ammonium carbonate.
- 9. The method according to claim 7, wherein the ammonium salt is ammonium acetate.
- 10. The method according to claim 7, wherein the molar ratio of said ammonium salt relative to said growth hormone is from about 10:1 to about 80:1.
- 11. The method according to claim 1, wherein the biodegradable polymer is lactic acid/glycolic acid polymer.
- 12. The method according to claim 11, wherein said biodegradable polymer has a ratio of lactic acid to glycolic acid of from about 100:0 to about 40:60.
- 13. The method according to claim 11, wherein the biodegradable polymer comprises lactic acid/glycolic acid polymer having a weight-average molecular weight of about 3,000 to about 50,000.
- 14. The method according to claim 11, wherein the lactic acid/glycolic acid polymer is in a form of a polyvalent metal salt.
- 15. The method according to claim 14, wherein the polyvalent metal is zinc.
- 16. The method according to claim 1 further comprising micro-encapsulating said sustained-release preparation obtained in step d) to form microcapsules.
- 17. The method according to claim 16, wherein the average particle size of said microcapsules is from about 0.1 μm to about 300 μm.
- 18. The method according to claim 1, wherein the resulting sustained-release preparation is suitable for administration by injection.
- 19. A sustained-release preparation produced by the method according to claim 1.
- 20. A method for producing a growth hormone powder comprising the steps of:a) adding a volatile salt or a volatile salt and a water-miscible organic solvent into an aqueous solution of a growth hormone to form a product solution; and then b) lyophilizing said product solution of step a) to form a powder comprising particles wherein the average size of said particles is not more than about 10 μm.
- 21. A growth hormone powder which is obtained by the method according to claim 20.
- 22. A method of using said sustained release preparation of claim 1 for the manufacture of a medicament, said method comprising combining said sustained release preparation of claim 1 with a pharmaceutically acceptable carrier, diluent or excipient.
Priority Claims (1)
Number |
Date |
Country |
Kind |
10-071853 |
Mar 1998 |
JP |
|
Parent Case Info
This Application is the National Stage of International Application Serial No. PCT/JP99/01359, filed Mar. 18, 1999.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/JP99/01359 |
|
WO |
00 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO99/48519 |
9/30/1999 |
WO |
A |
US Referenced Citations (5)
Number |
Name |
Date |
Kind |
5478564 |
Wantier et al. |
Dec 1995 |
A |
5609886 |
Wantier et al. |
Mar 1997 |
A |
5654010 |
Johnson et al. |
Aug 1997 |
A |
5667808 |
Johnson et al. |
Sep 1997 |
A |
6087324 |
Igari et al. |
Jul 2000 |
A |
Foreign Referenced Citations (11)
Number |
Date |
Country |
0251476 |
Jan 1988 |
EP |
0633020 |
Nov 1995 |
EP |
0891774 |
Jan 1999 |
EP |
WO 9013285 |
Nov 1990 |
WO |
WO 9112882 |
Sep 1993 |
WO |
WO 9409898 |
May 1994 |
WO |
WO 9412158 |
Jun 1994 |
WO |
9701331 |
Jan 1997 |
WO |
WO 9735563 |
Oct 1997 |
WO |
WO 9827980 |
Jul 1998 |
WO |
912239 |
Mar 1991 |
ZA |
Non-Patent Literature Citations (2)
Entry |
R. Jeyanthi et al., “Effect of processing parameters on the properties of peptide-containing PLGA microspheres” J. Microencapsulation, 14(2),Mar.-Apr. 1997, pp. 163-174. |
Overcashier et al., “Preparation of Excipient-free Recombinant Human Tissue-Type Plasminogen Activator by . . . ” Journal of Pharmaceutical Sciences, vol. 86, No. 4, pp. 455-459 (1997). |