The present invention provides methods for producing a lyophilized degarelix product which, upon reconstitution with water for injection in an amount of 20 mg/ml, shows a viscosity of up to 15 mPas. The present invention also provides a lyophilized degarelix drug substance which shows, upon dissolut
The present invention provides methods for producing a lyophilized degarelix product which, upon reconstitution with water for injection in an amount of 20 mg/ml, shows a viscosity of up to 15 mPas. The present invention also provides a lyophilized degarelix drug substance which shows, upon dissolution in water in an amount of 20 mg/ml, a viscosity of up to 3.2 mPas, and processes for providing this lyophilized degarelix drug substance.
대표청구항▼
1. A method for producing a degarelix drug substance comprising the steps of: a. Purifying degarelix as obtained by liquid or solid phase peptide synthesis to obtain a degarelix solution with a purity of at least 95%, as determined by high performance liquid chromatography (HPLC);b. Evaporating from
1. A method for producing a degarelix drug substance comprising the steps of: a. Purifying degarelix as obtained by liquid or solid phase peptide synthesis to obtain a degarelix solution with a purity of at least 95%, as determined by high performance liquid chromatography (HPLC);b. Evaporating from the degarelix solution solvent to concentrate the degarelix solution to obtain aggregated degarelix;c. Deaggregating the aggregated degarelix with acetic acid; andd. Lyophilizing the deaggregated degarelix to provide the degarelix drug substance. 2. The method according to claim 1, wherein the acetic acid concentration at the end of step c is in the range of 15 to 35% (v/v). 3. The method according to claim 1, wherein the temperature in step c is in the range of −5 to 30° C. 4. The method according to claim 1, wherein the degarelix concentration (free base) is in the range of 10 to 35 g/l in step c. 5. A method for producing a degarelix drug substance comprising the steps of: a. Purifying degarelix as obtained by liquid or solid phase peptide synthesis to obtain a degarelix solution with a purity of at least 95%, as determined by HPLC;b. Loading the degarelix solution onto a chromatographic column;c. Eluting degarelix from the column with acetic acid to provide eluted degarelix, wherein the acetic acid concentration is in the range of 27 to 37 wt. %;d. Lyophilizing the eluted degarelix to provide the degarelix drug substance. 6. The method according to claim 5, wherein the eluted degarelix is filtered prior to lyophilization. 7. A method for producing a degarelix drug substance comprising the steps of: a. Purifying degarelix as obtained by liquid or solid phase peptide synthesis to obtain a degarelix solution with a purity of at least 95%, as determined by HPLC;b. Adjusting the acetic acid concentration of the purified degarelix solution to 6 to 40% (w/w), if necessary; andc. Spray-drying the degarelix solution to provide the degarelix drug substance. 8. A method for producing a lyophilized degarelix drug product, wherein the lyophilized degarelix drug product provides, upon reconstitution with a liquid in an amount of 20 mg degarelix free base/ml, a viscosity of up to 15 mPas, comprising the steps of: a. Dissolving a lyophilized degarelix drug substance in a mannitol containing aqueous solution to provide a degarelix-mannitol mixture; andb. Lyophilizing the degarelix-mannitol mixture to provide the lyophilized degarelix drug product, wherein a non-ionic surfactant is added to the degarelix-mannitol mixture prior to lyophilization. 9. The method according to claim 8, wherein the non-ionic surfactant is Polysorbate 20 or Tocopheryl-polyethylene-glycol-1000-succinate. 10. The method according to claim 8, wherein the lyophilized degarelix drug product, upon reconstitution with the liquid, comprises the non-ionic surfactant in an amount ranging from 0.1 mg/ml to 5 mg/ml. 11. The method according to claim 8, wherein the lyophilized degarelix drug substance provides, upon dissolution in an amount of 20 mg degarelix free base/ml in water containing mannitol (2.5% w/V), a viscosity of more than 3.2 mPas. 12. A degarelix drug product comprising a lyophilized degarelix drug product and a non-ionic surfactant, wherein the drug product provides, upon reconstitution with a liquid in an amount of 20 mg degarelix free base/ml, a viscosity of up to 15 mPas, and the non-ionic surfactant is present in an amount of 0.001 mg/ml to 5 mg/ml. 13. The method according to claim 12, wherein the viscosity ranges from 2 to 12 mPas. 14. The method according to claim 8, wherein the viscosity ranges from 2 to 12 mPas.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (10)
Rivier Jean E. F. (La Jolla CA) Porter John S. (Leucadia CA) Hoeger Carl A. (San Marcos CA) Jiang Guangcheng (La Jolla CA) Rivier Catherine L. (La Jolla CA), GNRH antagonists XIII.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.