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):	Sun Kaoxiang, Liang Rongcai, Wang Qilin, Wang Wenyan, Liu Wanhui, Li Youxin
Assignee:
Application Number:	US16144614
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; anda 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; andwherein 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 claim 1 , 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 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 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 claim 1 ,000-145 claim 1 ,000 claim 1 , and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 4 claim 1 ,000-45 claim 1 ,000.7. The pharmaceutical composition according to wherein the first uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 55 claim 6 ,000-110 claim 6 ,000; and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 4 claim 6 ,000-35 claim 6 ,000.8. The pharmaceutical composition according to wherein the first uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 55 claim 7 ,000-85 claim 7 ,000; and the second uncapped poly(lactide-co-glycolide) has a weight average molecular weight of 15 claim 7 ,000-35 claim 7 ,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 claim 1 , the weight content of the polymer blend is 55% of the microspheres claim 1 , the weight ratio of the first uncapped PLGA to the second uncapped PLGA is 80:20 claim 1 , the molecular weight of the first uncapped PLGA is 55 claim 1 ,000 to 85 claim 1 ,000 and the molecular weight of the second uncapped PLGA is 15 claim 1 ,000 to 35 claim 1 ,000 claim 1 , 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 claim 1 , 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 claim 1 , hydrobromate claim 1 , nitrate claim 1 , sulfate and phosphate; and the organic acid salt being selected from acetate claim 1 , propionate claim 1 , hydroxy acetate claim 1 , 2-hydroxy propionate claim 1 , pamoate claim 1 , 2-oxo propionate claim 1 , oxalate claim 1 , malonate claim 1 , succinate claim 1 , 2-butenedioate claim 1 , methanesulfonate claim 1 , ethanesulfonate claim 1 , benzenesulfonate and toluenesulfonate.17. A sustained release injectable formulation comprising the pharmaceutical composition of and a pharmaceutically acceptable excipient.18. The sustained release injectable formulation of wherein the pharmaceutically acceptable excipient is a suspending agent claim 17 , a pH regulator claim 17 , an isoosmotic adjusting agent claim 17 , a surfactant claim 17 , water claim 17 , physiological saline or a combination thereof; and wherein the suspending agent is selected from sodium carboxymethyl cellulose claim 17 , polyvinyl alcohol claim 17 , polyvinyl pyrrolidone claim 17 , sodium alginate claim 17 , and glycerol; and wherein the isoosmotic adjusting agent is selected from sodium chloride claim 17 , glucose claim 17 , mannitol claim 17 , 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 claim 17 , the method comprising administering to the subject a sustained release injectable formulation of claim 17 , wherein the psychosis is acute schizophrenia claim 17 , chronic schizophrenia claim 17 , significant positive symptoms claim 17 , significant negative symptoms of other psychotic states claim 17 , and affective symptoms related to schizophrenia.20. The method of wherein the pharmaceutical composition releases the active component in a sustained manner for a period of up to 28 days.