Claims for Patent: 10,098,882

Summary for Patent: 10,098,882

Title:	Risperidone sustained release microsphere composition
Abstract:	A risperidone sustained release microsphere formulation is provided. The microsphere formulation includes risperidone or 9-hydroxy risperidone or salts thereof, and a polymer blend having a first uncapped lactide-glycolide copolymer and a second uncapped lactide-glycolide copolymer, in which the first uncapped lactide-glycolide copolymer is a copolymer with a high intrinsic viscosity and the second uncapped lactide-glycolide copolymer is a copolymer with a low intrinsic viscosity. The sustained release micro sphere formulation according to an embodiment of the present disclosure is suitable for large-scale industrialized production with improved stability, the in vivo release behavior of which will not change after long-term storage.
Inventor(s):	Kaoxiang Sun, Rongcai Liang, Qilin Wang, Wenyan Wang, Wanhui Liu, Youxin Li
Assignee:	Luye Innomind Pharma Shijiazhuang Co Ltd
Application Number:	US15/347,365
Patent Claims:	1. Microspheres for sustained release of an active agent comprising: an active component selected from the group consisting of risperidone, 9-hydroxy risperidone, a salt of risperidone, and a salt of 9-hydroxy risperidone; and a polymer blend consisting essentially of a first uncapped poly(lactide-co-glycolide) and a second uncapped poly(lactide-co-glycolide), wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.4-0.9 dl/g and a molar ratio of lactide to glycolide of 65:35 to 90:10; and wherein the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.1-0.35 dl/g and a molar ratio of lactide to glycolide of 50:50 to 75:25. 2. The microspheres of claim 1, wherein the molar ratio of lactide to glycolide in the first uncapped poly(lactide-co-glycolide) is 75:25; and wherein the molar ratio of lactide to glycolide in the second uncapped poly(lactide-co-glycolide) is 50:50. 3. The microspheres of claim 1, wherein a weight ratio of the first uncapped poly(lactide-co-glycolide) to the second uncapped poly(lactide-co-glycolide) is in a range from 50:50 to 95:5. 4. The microspheres of claim 1, wherein the first uncapped poly(lactide-co-glycolide) has a molecular weight from 50,000 to 145,000; and wherein the second uncapped poly(lactide-co-glycolide) has a molecular weight from 4,000 to 45,000. 5. The microspheres of claim 1, wherein the active agent is in an amount of from 10% to 60% based on a total weight of the microspheres. 6. Microspheres for sustained release of an active agent comprising: an active agent selected from the group consisting of risperidone, 9-hydroxy risperidone, a salt of risperidone, and a salt of 9-hydroxy risperidone; and a polymer blend consisting essentially of a first uncapped poly(lactide-co-glycolide) and a second uncapped poly(lactide-co-glycolide); wherein the first uncapped poly(lactide-co-glycolide) has a molecular weight from 50,000 to 145,000 and a molar ratio of lactide to glycolide in a range from 65:35 to 90:10; wherein the second uncapped poly(lactide-co-glycolide) has a molecular weight from 4,000 to 45,000 and a molar ratio of lactide to glycolide in a range from 50:50 to 75:25. 7. The microspheres of claim 6, wherein the first uncapped poly(lactide-co-glycolide) has a molecular weight from 55,000 to 110,000; and wherein the second uncapped poly(lactide-co-glycolide) has a molecular weight from 15,000 to 35,000. 8. The microspheres of claim 6, wherein the molar ratio of lactide to glycolide in the first uncapped poly(lactide-co-glycolide) is 75:25; and wherein the molar ratio of lactide to glycolide in the second uncapped poly(lactide-co-glycolide) is 50:50. 9. The microspheres of claim 6, wherein a weight ratio of the first uncapped poly(lactide-co-glycolide) to the second uncapped poly(lactide-co-glycolide) is in a range from 50:50 to 95:5. 10. The microspheres of claim 6, wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.4-0.9 dl/g; and wherein the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.1-0.35 dl/g. 11. The microspheres of claim 6, wherein the active agent is in an amount of from 10% to 60% based on a total weight of the microspheres. 12. Microspheres for sustained release of an active agent comprising: an active agent selected from the group consisting of risperidone, 9-hydroxy risperidone, a salt of risperidone, and a salt of 9-hydroxy risperidone; and a polymer blend comprising a first uncapped poly(lactide-co-glycolide) and a second uncapped poly(lactide-co-glycolide); wherein the first uncapped poly(lactide-co-glycolide) has a molecular weight from 55,000 to 110,000, an intrinsic viscosity of 0.4-0.9 dl/g, and a molar ratio of lactide to glycolide in a range from 65:35 to 90:10; wherein the second uncapped poly(lactide-co-glycolide) has a molecular weight from 15,000 to 35,000, an intrinsic viscosity of 0.1-0.35 dl/g, and a molar ratio of lactide to glycolide in a range from 50:50 to 75:25; and wherein a weight ratio of the first uncapped poly(lactide-co-glycolide) to the second uncapped poly(lactide-co-glycolide) is in a range from 50:50 to 95:5, such that lactide is a major monomer component compared to glycolide of the polymer blend. 13. The microspheres of claim 12, wherein the active agent is in an amount of from 10% to 60% based on a total weight of the microspheres. 14. The microspheres of claim 13, wherein no crystals of the active agent are precipitated on the surfaces of the microspheres. 15. A pharmaceutical formulation for injection into a patient in need, comprising: the microspheres of claim 1. 16. A method of treating a psychosis comprising: administering parenterally a therapeutically effective amount of the pharmaceutical formulation of claim 15 to a patient in need. 17. The method of claim 16, wherein the administrating method is intramuscular injection, subcutaneous injection, intradermal injection, or intraperitoneal injection. 18. The method of claim 16, wherein each administration dose provides 12.5 to 150 mg of risperidone. 19. The method of claim 16, wherein the therapeutically effective amount is 0.2 to 2.5 mg risperidone per kg of body weight. 20. The method of claim 16, wherein the therapeutically effective amount is 0.4 to 1.7 mg risperidone per kg of body weight. 21. A method of treating psychosis in a patient in need thereof, the method comprising: administering parenterally to the patient a therapeutically effective amount of a pharmaceutical formulation comprising a plurality of microspheres including (1) an active component selected from the group consisting of risperidone, 9-hydroxy risperidone, a salt of risperidone, and a salt of 9-hydroxy risperidone; and (2) a polymer blend consisting essentially of a first uncapped poly(lactide-co-glycolide) and a second uncapped poly(lactide-co-glycolide), wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.4-0.9 dl/g and a molar ratio of lactide to glycolide of 65:35 to 90:10; wherein the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.1-0.35 dl/g and a molar ratio of lactide to glycolide of 50:50 to 75:25, and the pharmaceutical formulation releases the active component in a sustained manner for a period of up to 28 days. 22. The method of claim 21 wherein the plurality of microspheres comprise 10% - 60% of the active component based on the total weight of the microspheres.