RU2002102725A - Growth Hormone Compositions - Google Patents

Claims (35)

1. Storage stable liquid growth hormone composition mainly comprising growth hormone in an isotonic phosphate buffered solution. 2. Storage stable liquid growth hormone composition, mainly including growth hormone in an isotonic phosphate buffered solution and preservative. 3. The composition according to claim 1 or 2, in which the compound that provides isotonicity is selected from the group comprising one or more monosaccharides, disaccharides and sugar alcohols. 4. The composition according to any one of claims 1 to 3, in which isotonicity is provided by mannitol and / or sucrose and / or optionally lactose. 5. The composition according to any one of claims 1 to 4, the pH of which is in the range from 5.6 to 6.5, or the pH is 6.2 or higher. 6. The composition according to any one of claims 1 to 4, the pH of which is in the range from 6.15 to 7.4, preferably in the range from 6.2 to 6.5. 7. The composition according to any one of claims 2 to 6, in which one or more compounds from the group consisting of phenol, benzyl alcohol, meta-cresol, methyl paraben, propyl paraben, benzalkonium chloride and benzethonium chloride are selected as a preservative. 8. Storage stable liquid growth hormone composition, mainly including growth hormone in phosphate buffered solution. 9. Storage stable liquid growth hormone composition, mainly including growth hormone in phosphate buffered saline and preservative. 10. A storage stable liquid growth hormone composition comprising growth hormone in a phosphate buffered solution and a nonionic surfactant at a concentration below about 0.01% (w / v). 11. The composition of claim 10, in which the nonionic surfactant is present in a concentration below about 0.001% (w / v). 12. The composition of claim 10 or 11, in which the phosphate buffer solution is isotonic, optionally a pH value in the range of 5.6 to 6.5, and which optionally further includes a preservative. 13. The composition of claim 12, wherein one or more compounds from the group consisting of phenol, benzyl alcohol, meta-cresol, methyl paraben, propyl paraben, benzalkonium chloride and benzethonium chloride are selected as a preservative. 14. The composition of claim 12, wherein the phosphate buffered solution is isotonic with a neutral salt, for example, NaCl, or a compound selected from monosaccharides, for example, lactose, disaccharides, for example, sucrose, or sugar alcohol, for example, mannitol. 15. The composition according to any one of the preceding paragraphs, in which the growth hormone is a human growth hormone. 16. The composition according to any one of the preceding paragraphs, in which the aggregation of growth hormone is less than 0.01%, preferably less than 0.1%, more preferably less than 1% and even more preferably less than 10% 17. A liquid composition of growth hormone having the following composition: hGH 3.33 mg / ml (10 IU / ml),

Mannitol 35 mg / ml (3.5% w / v), Pluronic F-68 2 mg / ml (0.2% w / v), Benzyl alcohol 9.00 mg / ml (i.e. 0.9% w / v), Water for injection pH q.s. 6.2. 18. The composition according to any one of the preceding paragraphs, in which during storage no appreciable crystallization occurs. 19. The composition according to p. 18, which can be stored for at least 1 month, preferably 6 weeks, more preferably for a period of time from about 1 to 4 months, most preferably 3 months. 20. The composition according to p. 18 or 19, which can be stored at a temperature of about 2 ° C or higher, preferably about 4 ° C or higher, more preferably at a temperature in the range of about 2 to less than 40 ° C, even more preferably at a temperature in the range of about 2 to 25 ° C, most preferably at 15 ° C. 21. The composition according to p. 18-20, in which the crystallization is a crystallization of growth hormone. 22. The composition according to any one of paragraphs 18-21, in which crystallization can be detected visually, preferably using a light microscope at 5x magnification, even more preferably using a light microscope at 10x magnification. 23. A device for administering a liquid composition to a patient by injection, comprising at least one unit dose of the composition according to any one of claims 1 to 22. 24. The device according to item 23, which is a manual injector. 25. The device according to item 23 or 24, intended for use by humans. 26. A kit comprising an injection device and a separate container with a composition according to any one of claims 1 to 22. 27. The kit according to p. 26, where the container is adapted to the used device for injection so that when applied, the composition in the container flows into the inlet of the device for injection. 28. The kit of claim 27, wherein the injection device is a manual injector and the container is a cartridge. 29. A cartridge containing a liquid composition according to any one of claims 1 to 22, intended for use in combination with a manual injector. 30. The use of an aqueous growth hormone composition comprising a phosphate buffer, the pH of which is about 6.2 or higher, as intended for storage of a pharmaceutical product in which crystallization practically does not occur. 31. The application of clause 30, where the pH of the phosphate buffer is in the range from 6.15 to 7.4, and / or the storage period is at least 1 month, and / or the storage temperature is approximately 2 ° C or higher. 32. The use of claim 30 or 31, wherein the composition comprises a nonionic surfactant, preferably at a concentration of about 0.2% (w / v). 33. A method for eliminating crystallization during storage of a phosphate-buffered aqueous growth hormone composition, the preparation of such a growth hormone composition having a pH of about 6.2 or higher. 34. The method according to p, where the pH value is in the range from 6.15 to 7.4, preferably 6.2-6.5 and / or the storage period is at least 1 month, and / or storage temperature is approximately 2 ° C or higher. 35. The method of claim 33 or 34, wherein the composition comprises a nonionic surfactant, preferably at a concentration of about 0.2% (w / v).