Claims for Patent: 10,406,161

Summary for Patent: 10,406,161

Title:	Risperidone sustained release microsphere composition
Abstract:	A risperidone sustained release microsphere formulation is provided. The microsphere formulation comprise 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 microsphere 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:	US16/144,614
Patent Claims:	1. A pharmaceutical composition comprising: a pharmaceutically active component selected from risperidone or a salt thereof, 9-hydroxy risperidone or a salt thereof; and a polymer blend comprising a first uncapped poly(lactide-co-glycolide) and a second uncapped poly(lactide-co-glycolide), wherein the polymer blend does not have a capped poly(lactide-co-glycolide), wherein the first uncapped poly(lactide-co-glycolide) has a molar ratio of lactide to glycolide of 65:35 to 90:10; and the second uncapped poly(lactide-co-glycolide) has a molar ratio of lactide to glycolide of 50:50 to 75:25; and wherein the pharmaceutical composition is in the form of microspheres. 2. The pharmaceutical composition according to claim 1, wherein the molar ratio of lactide to glycolide in the first uncapped poly(lactide-co-glycolide) is 75:25; and the molar ratio of lactide to glycolide in the second uncapped poly(lactide-co-glycolide) is 50:50. 3. The pharmaceutical composition according to claim 1, wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.4-0.9 dl/g, and the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.1-0.35 dl/g. 4. The pharmaceutical composition according to claim 3 wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.45-0.8 dl/g; and the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.1-0.3 dl/g. 5. The pharmaceutical composition according to claim 4 wherein the first uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.45-0.55 dl/g; and the second uncapped poly(lactide-co-glycolide) has an intrinsic viscosity of 0.2-0.3 dl/g. 6. The pharmaceutical composition according to claim 1, wherein the first uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 50,000-145,000, and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 4,000-45,000. 7. The pharmaceutical composition according to claim 6 wherein the first uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 55,000-110,000; and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 4,000-35,000. 8. The pharmaceutical composition according to claim 7 wherein the first uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 55,000-85,000; and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 15,000-35,000. 9. The pharmaceutical composition according to claim 1, wherein the first uncapped poly(lactide-co-glycolide) is present in the polymer blend at 50-95 wt % and the second uncapped poly(lactide-co-glycolide) is present in the polymer blend at 5-50 wt %. 10. The pharmaceutical composition according to claim 9, wherein the first uncapped poly(lactide-co-glycolide) is present in the polymer blend at 70-90 wt % and the second uncapped poly(lactide-co-glycolide) is present in the polymer blend at 10-30 wt %. 11. The pharmaceutical composition according to claim 10, wherein the first uncapped poly(lactide-co-glycolide) is present in the polymer blend at 80 wt % and the second uncapped poly(lactide-co-glycolide) is present in the polymer blend at 20 wt %. 12. The pharmaceutical composition according to claim 1, wherein a weight content of the pharmaceutically active component in the microspheres is within a range from 10% to 60%; and a weight content of the polymer blend in the microspheres is within a range from 40% to 90%. 13. The pharmaceutical composition according to claim 12, wherein a weight content of the pharmaceutically active component in the microspheres is within a range of 35%-55%; and a weight content of the polymer blend in the microspheres is within a range of 45%-65%. 14. The pharmaceutical composition according to claim 13, wherein a weight content of the pharmaceutically active component in the microspheres is within a range of 40%-50%; and a weight content of the polymer blend in the microspheres is within a range of 50%-60%. 15. The pharmaceutical composition according to claim 1, wherein the weight content of risperidone is 45% of the microspheres, the weight content of the polymer blend is 55% of the microspheres, the weight ratio of the first uncapped PLGA to the second uncapped PLGA is 80:20, the molecular weight of the first uncapped PLGA is 55,000 to 85,000 and the molecular weight of the second uncapped PLGA is 15,000 to 35,000, the intrinsic viscosity of the first uncapped PLGA is 0.45 to 0.55 dL/g and the intrinsic viscosity of the second uncapped PLGA is 0.2 to 0.3 dL/g, and a molar ratio of lactide to glycolide in the first uncapped PLGA is 75:25 and a molar ratio of lactide to glycolide in the second uncapped PLGA is 50:50. 16. The pharmaceutical composition according to claim 1, wherein the salt of risperidone or 9-hydroxy risperidone is selected from an inorganic acid salt and an organic acid salt; the inorganic acid salt being selected from hydrochlorate, hydrobromate, nitrate, sulfate and phosphate; and the organic acid salt being selected from acetate, propionate, hydroxy acetate, 2-hydroxy propionate, pamoate, 2-oxo propionate, oxalate, malonate, succinate, 2-butenedioate, methanesulfonate, ethanesulfonate, benzenesulfonate and toluenesulfonate. 17. A sustained release injectable formulation comprising the pharmaceutical composition of claim 1 and a pharmaceutically acceptable excipient. 18. The sustained release injectable formulation of claim 17 wherein the pharmaceutically acceptable excipient is a suspending agent, a pH regulator, an isoosmotic adjusting agent, a surfactant, water, physiological saline or a combination thereof; and wherein the suspending agent is selected from sodium carboxymethyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, sodium alginate, and glycerol; and wherein the isoosmotic adjusting agent is selected from sodium chloride, glucose, mannitol, and glucitol; and wherein the surfactant is a nonionic surfactant and is selected from polysorbate series and poloxamer series. 19. A method for treating psychosis in a subject in need of treatment, the method comprising administering to the subject a sustained release injectable formulation of claim 17, wherein the psychosis is acute schizophrenia, chronic schizophrenia, significant positive symptoms, significant negative symptoms of other psychotic states, and affective symptoms related to schizophrenia. 20. The method of claim 19 wherein the pharmaceutical composition releases the active component in a sustained manner for a period of up to 28 days.