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吡喹酮植入剂的制备及体外释放的研究程亮,郭圣荣A1A0A2A3A4A5A6A7A6A8A9A0A2200240A10A11A12A13A14A15A16A17A18A19A20PZQA21A22A23A24A25A26A27A28A29A30A31A32A33A34A35A36A37A38A39A40A41A42A43A44A45A38A46A47A48A49A50A51A20PCLA21A52A48A53A54A551500A20PEG1500A21A56A57A58A59A60A15A16A17A18A19A22A23A24A46A25A40NMRA61HPLCA61XRDA61FSEMA26A62A63A64A15A16A65A66A67A14A41A68A69A70A61A62A63A64A22A23A24A67A14A71A72A73A74A75A61A62A63A64A22A23A24A67A14A63A76A77A78A52A22A23A24A30A31A79A80A14A81A82A32A33A83A34A35A84A85A62A63A64A15A16A65A66A67A86A87A88A89A90A91A46A62A63A14A71A72A73A74A75A73A6480A92A93120A92A14A94A69A95A96A46A62A63A14A84A97A75A98A99PEG1500A71A72A14A100A101A102A103A104A105A106A46A62A63A14A30A31A107A75A98A99PEG1500A71A72A14A100A101A102A103A104A101A108A46A28A29A30A31A109A110HIGUCHIA30A31A111A112A36A84A113A41A42A43A44A45A38A15A16A17A18A19A22A23A24A114A115A116A33A46A62A63A14A30A31A116A47A117A65A118A119PEG1500A71A72A32A33A120A121A36A122A123A124A12A17A18A19A125A48A49A50A51A125A48A53A54A55A125A22A23A24A125A28A29A30A31A67A126A90A127A128A12A129A130A131A132A133A12A129A134A135A128A12STUDYONPREPARATIONANDINVITRODRUGRELEASEOFPRAZIQUANTELIMPLANTSCHENGLIANG,GUOSHENGRONGPHARMACYSCHOOLOFSHANGHAIJIAOTONGUNIVERSITY,SHANGHAI200240ABSTRACTOBJECTIVETOPREPAREPRAZIQUANTELIMPLANTSANDINVESTIGATETHEINVITRODRUGRELEASEMETHODSPRAZIQUANTELCONTAINEDIMPLANTSWEREFABRICATEDBYHOTMELTINGEXTRUSION,ANDPCLA136PEG1500WERECHOSENASTHEMATRIXTHETHERMALSTABILITYOFPZQDURINGTHEPROCESSWASANALYZEDBYNMRTHEDRUGCONTENTUNIFORMITYWASDETERMINEDBYHPLCTHEPHYSICALSTATEOFPZQINTHEIMPLANTSWASSTUDIEDUSINGXRDTHESURFACEANDCROSSSECTIONALMORPHOLOGYOFIMPLANTSWEREOBSERVEDBYSEMRESULTSPZQWASSTABLEDURINGTHEFABRICATIONPROCESSTHEDRUGWASDISPERSEDUNIFORMLYINTHEIMPLANTSANDTHEDRUGCONTENTUNIFORMITYWASINTHERANGEOF80A137A138120A137WITHTHEINCREASINGCONTENTOFPEG1500INTHEIMPLANTS,THEDRUGRELEASERATEWASACCELERATEDANDTHECRYSTALLINEOFPZQWASDEPRESSEDTHEINVITRODRUGRELEASEWASFITTEDWELLWITHHIGUCHIEQUATIONCONCLUSIONTHEHOTMELTINGEXTRUSIONMETHODISFEASIBLETOPREPAREPRAZIQUANTELCONTAINEDIMPLANTS,THEINVITRODRUGRELEASECANBEADJUSTEDBYCHANGINGTHECONTENTOFPEG1500KEYWORDSPRAZIQUANTELPOLYCAPROLACTONEPOLYETHYLENEIMPLANTSINVITRODRUGRELEASEA139A140A141A142HYDATIDDISEASEA143A144A145A146A147A148A149A141A150A151A152A147A148A153A154A140A155A156A157A158A159A160A161A162A163A140A141A164A165A166A139A140A141A157A167A168A169A170A171A172A173A174A175A157A159A176A177A150A178A179A180A181A182A183A184A185A186A187A188A189A190A188A191A192A1931A194A1951A1961A197A198A199A200A201A202A188A189A203A204A205A206A193A205A207A203A204A208A209A210A203A204A211A205A207A203A204A189A212A213A214A215A216A217A218A219A200A220A221A222A223A224A225A226A204A227A228A189A229A230A231A218A219A200A232A182A233A234A235A186A236A237A238A214A239A209A210A203A204A240A241A242A243A223A244A245A212A213A246A247A245A248A249A241A250A251A252A253A200A232A193A254A255A203A204A201A202A188A189A189A0A223A1A197A205A2A200A206A3A189A242A243A223A4A200A209A5A211A242A243A200A212A6A7A182A8A253A9A10A211A217A243A53A189A11A12A217A218A13A200A5A211A243A53A210A200A221A14A243A53A15A9A16A17A249A12A82A18A19A224A20A21A239A228A137A22A23A189A24A250A25A200A232A26A27A20A21A189A243A53A200A235A221A14A28A29A30A212A19A243A31A32A217A189A33A53A200A241A34A243A53A189A35A36A191A218A246A239A244A245A37A222A188A189A38A39A40A41A200A5A211A243A53A189A203A204A204A40A42A43A1931A250A44A252A250A9A251A200A253A45A185A5A211A243A53A242A188A46A47A48A74A49A50A51A52A200A54A55A200A218A219A189A5A211A179A56A57A58A33A240A59A243A2172,3A197A60A61A242A243A62A3A63IMPLANTABLEDRUGDELIVERYSYSTEMSA64A2A65A66A48A67A179A68A69A189A70A253A200A243A53A42A24A60A61A242A243A9A71A107A237A241A250A72A73A23A189A189A24A250A25A200A18A75A76A107A237A57A235A40A41A185A77A219A243A53A189A240A53A35A36A41A200A78A79A242A243A189A80A2524A197A182A199A81A189A68A69A83A200A254A84A85A36A86A70A87A88A89A90A224A67A91A74A92A93A237A94A95A96A97A193A98A99A189A100A101A102A60A61A179A200A103A55A104A105A106A108A200A243A53A107A237A109A110A104A105A111A112100A113A237A183A200A218A110A189A243A53A104A105A114A191A107A16A112A9A44A241A250A189A203A204A115A41A200A15A187A254A84A42A24A116A86A117A11A217A189PEGA48A118A119A243A53A189A104A105A197A213A68A69A67A91A74A237PEGA245PCLA193A120A121A98A99A189A100A101A102A60A61A179A200A122A123A124A74A243A53A182PEGA245PCLA120A121A98A99A83A189A103A96A55A104A105A1971仪器与材料11A125A126A127A128A129A130A131A13299A133A134A160A135A136A138A173A139A140A141A142A143A144A145A146A147A148A149A150A248A151A152A153A154A15550000A145A156A176A157A158A159A161A162A163A164A144A145A146A165A166A1671500A150A168A169A170A171A172A174A175A177A161A162A163A164A144A145A178A167A150A180A181A182A145A183A184A185A186A187A172A161A162A163A164A144A145A188A190A175A177A151A155A152A191A182A19212A193A194A195A196A197A198A199A200A201A202SHIMADZULC10ADA203A204SHIMADZUSPD10ADVPA207A208A213A214A215A204SHIMADZUA216A218A219A220A222DIKMAC18A223A224A225A226A227A2294A230A231A233A234A236A237A237A222A238A239A234A242A237A220TGL16GA243A246A247A226A249A251A229A254A255A196A85A0A174A64A1A2A220A222QL901A243A88A3A4A101A1A229A90A5A255A6A7A8A9A184A10A64A1A2A220A222A96A79A97A11A12A13A14A158A15A16A229FSEMA222JEOL7401FA222A49A176JEOLA46A17A220A222XA97A18A19A97A64A229XRDA222A49A176RIGAKUA46A17A220A202实验方法21植入剂的制备A30A10A21A22A23A24A25A26A229HOTMELTINGEXTRUSIONA220A27A28A29A31A32A33A34A35A222A209A105A36A60A37A38A106A225A107A225A108A132A109PZQA52PCLA52PEGA222A110A229A39A40A58,A10A112A41A42A4A10130MINA71A222A115A43A116A34A44A117A45A47A88A48A50A64A58A222A92A21A121A22A23A222A51A122A53A54A5520MINA222A92A21A218A66A5670A126A222A54A55A247A66A5645RPMA20A127A22A23A57A128A173A71A222A115A59A44A251A128A61A225A130A61A131A62A222A51A133A63A229A135A27A251A136A97A1A58A222A22970A126A185A65A137A115A22A23A251A128A61A225A130A61A24A34A44A67A239A563MMA251A138A227A68A69A70A58A222A139A218A72A73A128A173A71A222A142A69A222A51A115A74A59A138A42A144A175A75A66A5620MMA251A33A34A35A2022植入剂中药物含量均匀度的测定221A76A77A78A80A77A78A81A82A83A84DIKMAC18A83A864A87A89A91A93A94A95A95A98A93A99A95A100A102A120A103A104A84A111A113A146A218A86A147A114A114A118A119A114A123A124A125A129A134A147A140A114A141A143A152A141A145A148A149A150A124A151A153A134A155A114A154A124A156A157A159A160A134A161A162A155A148A141A163222A164A165A166A167A165A166A168A169A170A171A172A177A178A179A180A181A182A183A171A172A177A186A187A188A189A219A190A1912MLA192A193A194A195A197A198A199A2008MLA201A202A203A204PCLA195A205A206A207A208A210A21110000RPMA212A213A214A21515MINA195A216A217A220A221A210A195A222A223A224A225A226A224A198A195A217A22720ULA228A211HPLCA230A231A232223A233A234A235A236A237A234A235A238100A2391000A2392000MGA240A241A242A243A244A245A246A247A248A247A249A250A252A253A254A255A36A66A0A172A1A2A55A46A3A62A37A229A27A4A41A0A5A6A7A175A8A60A3A62A0A176A9A10A37A179A11A12A41A181A13A66A37A12A41A183A14A15A81A108A47A76A16A17A76A83A37A147A16A18A19A83A37A147A16A147A252A83A20A186A21A18A4A8A60A3A62A0A176A9A10A37A179A11A12A175A181A13A66A37A12A175A183A14A15A81A108A47A76A16A22A18A83A37A147A16A17A18A83A37A78A16A23A19A83A24224A25A26A28A29A30A26A28A81A108A181A13A132A10910A3150A31100MGPZQA25110MLA189A63A190A58A31A92A3250MGA191A33A34A32A35A31A105222A193A38A39A40A42A43PCLA71A31A226A441MLA160A167A45A25110MLA189A63A190A58A48A49A50A51A52A189A53A54A56A103A57A59A49HPLCA61A68A52A199A227A64A31A97A65A58A65A1803A171A67A63A69A56A70A199A227A64A72A73A1369999A74A3110008A74A319999A74A31A100A75A77A79A57225A80A82A84A85A86A87A88A89A90A91A82A84A86A87A88A89A200A93A94A95A96A98A99A101A102A104A10610A154A107A110A111A112A113A114A115222A116A117A118A119A114A120A121A107A110A111A122A123A124A125A126A127A128A201A202A122A129A124A203A2042005A130A131A133A134A135A137A107A110A111A122A124A125A126A127A138A139A140A128A124A125A126A127A138A139A140A206A107A110A111A122A207A141A124A125A127/A107A110A111A122A142A143A124A125A127A144100A14523药物稳定性考察A146A148A149A1503A154A107A110A111A112A113A114A115222A116A117A118A119A114A151A150A197A152A153A155A156A114A1575A158A159A218A209A185A161A117A114A162A163A164A165A166A148A219A111A114A168A169A170A173A125A174A219A177A157A213A237A214A178A114A182A184A216A187A188A192A194A195A128A119A196A198A201A114A205A208A124A210A184A216A187A188A192A194A195A12824X射线衍射分析A107A110A111A112A113A122A220A211A212A194A123A125A142A215A217A184XRDA221A222A194A195A114A221A222A223A140A224A225A196A228A230A2314A228A230A114PCLA232PEG1500A233PZQA119A196A198A201A12825吡喹酮植入剂的体外释放A234A235A236A107A110A111A122A146A148A149A1503A154A107A110A111A112A113A114A238A11030MLA239A240A241A242A243A122A114A244A110A245A246A247A248A123A249A250A252A17425MLA25302A145SDSA218A219A156A254A114A255A1103A188A159A123A218A209A209A0A192A1A2A122A128A55A231A121A123A60A175A201A114A151A150A249A250A156A228A79A3A114A158A78A4A228A82A79A169A5A56A169A71A184A157A232A6A7A8A194A195A114A181A60A235A9A197A152A249A250A252A174A12826植入剂形貌考察A107A110A111A55A249A250A13A71A123A29A10A233A144A10A72A11A184A96A12A97A221A222A14A15A16A26A128A107A110A111A112A113A55A16A26A13A140A17A165A23948HA114A240A71A241A183MINA114A16A26A14A100A1961KVA114A16A26A14A19A19620MAA1283结果与讨论31植入剂的制备A30A184A32A20A21A22A23A24A248A25A107A110A111A239A166A118A119A194A27A232A225A166A148A219A111A246A28A232A212A31A33A34A35A36A201A114A205A37A137A157A38A39A123A248A25A0A140A114A94A40A157A124A125A123A41A121A42A114A181A60A55A43A44A56A45A122A114A124A125A249A46A190A47A250A48A138A139A194A130A157A229A208A49A174A1225A128A196A50A252A211A47A153A94A40A51A253A114A31A207A207A203A52A50A53A211A38A33A123A118A119A0A1407A158A159A114A233A235A54A123A43A44A60A17520MINA128A137A571A107A58A114A234A107A110A111A122A59A150A123PZQA61A205A208A124PZQA239A166A192A62A53A63A123A216A187A57A64A114A29A65PZQA55A244A32A66A142A56A45A122A67A166A12A68A194A177A128A137A292A107A58A114A220A211A66A69A70A212A123A107A110A111A112A113A122A123PZQA126A127A138A139A140A138A66A15780A145A231120A145A224A225A114A29A65A124A125A55A107A110A111A122A194A130A73A194A138A139A128A291A107A110A111A122A207A141A124A127A253NA20610A254TABLE1THEACTUALDRUGLOADINGOFTHEIMPLANTSN10SAMPLEFORMULATIONSTHEORETICALDRUGLOADINGTHEPERCENTAGEOFACTUALDRUGLOADINGPZQPEGPCL,W/WTOTHEORETICALDRUGLOADINGA74A75A184A76A7715005050998A75A147A78A80250545501014A75A158A78A81350104050996A75A80A78A834502030501006A75A155A78A80550302050988A75A80A78A4A571A84PZQA233A59A150PZQA123A216A187A188A192A57FIG1H1NMRSPECTRAOFPUREPZQANDEXTRACTEDPZQAPUREPZQBEXTRACTEDPZQ32X射线衍射分析A6A172A174A232A6A85A86A147A228A158A158A232A6A8A7A233A220A211A66A69A123A107A110A111A112A113A123A87A183A76A57A64A58A57A80A128A137A57A80A107A47A88A23A114A89A6A85A86A147A228A158A158A126A127A90A228A145A60A253A91A92A93A95A92A98A99A101A102A103A104A105A106A108A109A110A111A112A113A92A98A99A101A114A103A104A105A106A115A116A117A118A119A120A121A122A123A98A124A125A126A127A128A128A129A131A132A126A128A133A182A134A135A92A136A92A138A95A92A98A99A101A102A103A104A139A141A142A98A124A125A126A127A128A128A129A131A102A143A145A146A148A149A150A151A92A152A153A154A156A157A117A98A99A101A103A104A158A115A159A160A117A98A124A125A126A127A128A128A102A161A162A163A164A165A92A176A103A166A167HAESSLEIN6A199A168A251A102A170A171A103A166A173A177A178A179A98A180A185A186A98A124A125A126A127A128A128A187A189A109A118A119A120A191A193A121A195A114A158A115A103A104A105A106A196A187A179ABA1972PCLA198PEGA198PZQA186A148A200PEGA129A131A102A118A119A120A191A193A102XA202A204A206A202A197FIG2THEXRDDIFFRACTIONPATTERNSOFAPCLBPEGCPZQDHIMPLANTSWITHDIFFERENTPEGCONTENTOF0,5,10,20,30,RESPECTIVELY,ANDTHEDRUGCONTENTOFIMPLANTSWASCONSTANTAT5033植入剂的体外释放A208A210A212A213A214A215A168A102A118A119A120A102A216A217A218A219A220A204A221A1973A92A153A114A222A223A141A142PEG1500A129A131A102A143A145A92PZQA102A218A219A224A226A148A149A145A227A920A133PEG1500A102A118A119A120A153A114A228A230A218A219A233A234A236A251100DA114A237A9230A133PEG1500A102A118A119A120A238A24225DA243A244A245A153A247A248A218A219A233A234A92A152A153A154A156A157A117A114A254A255A212A171A222A34A175A102A31PEG1500A192A109A35A0A102A5A159A1A92A123A118A119A120A167A218A219A62A37A2A71A92PEG1500A39A227A159A160A251A218A219A62A121A92A157A137A187A118A119A120A121A247A254A4A6A7A40A92A8A235A9A143A145A10PZQA167A218A219A62A102A37A2A177A11A92A200A146A143A145A10A233A234A102A159A223A1222PEG1500A47A27A41A38A42A170A12A13A234A92A192A109A27A162A102A29A177A239A1A120A102A195A31A92A154A43A143A145PZQA187A218A219A62A121A102A159A160A139A92A200A146A143A145A233A234A102A159A223A179A147A26A14A162A10PZQA187A148A200PEG1500A129A131A102A5A159A62A121A102A159A160A139A92A79A44PZQA18730A133PEG1500A5A159A62A121A102A159A160A139A107A187A15A5A121A102A159A160A139A143A235A103A45A1793A141A142PEG1500A187A118A119A120A121A129A131A102A143A145A92A16A6A102PZQA114A161A162A163A17/A46A115A48A106A196A187A92A152A188A143A145A10PZQA187A218A219A62A121A102A159A160A139A92A200A146A109A93A117A233A234A102A159A223A179A1973A148A200PEGA129A131A102A118A119A120A102A216A217A218A219A220A204A197FIG3INVITRORELEASEPROFILESOFPZQFROMIMPLANTSWITHDIFFERENTPEGCONTENTIN02SDSAQUEOUSSOLUTIONAT37A126A18,0PEGA19,5PEG,10PEG,20PEG,30PEGN3A20A21A216A217A218A219A103A166A31A148A200A102A218A219A22A163A134A23A58A218A219A22A163A92A27A58A218A219A22A163A92HIGUCHIA218A219A22A163A95A24A25A49A178A92A200A182A31RITGERPEPPASA214A28A21A118A119A120A102A216A217A218A219A84A215A24A25A10A30A32A92A103A166A221A292A179A157A179A33A103A166A153A114A50A162A118A119A120A102A216A217A218A219A60A178HIGUCHIA218A219A22A163A92A233A234A200A118A119A120A121A218A219A102A84A215A47A51A36A52A116A167A159A54A173A103A178A102A214A75A179A292A218A219A220A204A102A49A178A103A166TABLE2DATAFROMREGRESSIONFITTINGBETWEENDISSOLUTIONPROFILESANDSEVERALKINETICMODELSZEROORDER,FIRSTORDER,HIGUCHIANDTHERITGERPEPPASMODELRELEASEMECHANISMTHEFITTINGOFTHEDIFFERENTMODELSANDTHEDISSOLUTIONPROFILESISEXPRESSEDVIATHECORRELATIONCOEFFICIENTR,THERELEASEMECHANISMISIDENTIFIEDVIANVALUES34植入剂的形貌考察A210A212A213A214A102A118A119A120A191A193A187A218A219A55A71A102A29A177A186A144A177A72A53A221A1974A179A157A1974A134AA92BA95A153A221A92A118A119A120A187A218A219A55A192A109A107A56A57A182A102A29A177A186A144A177A72A53A92A29A59A187A61A63A64A140A65A66A173A67A28A121A92A68A69A70A73FORMULATIONZEROORDERRFIRSTORDERRHIGUCHIRRITGERPEPPASRN0PEG08969067300997009883069775PEG083700637209961099750695310PEG085870653209996099560720220PEG085300640709993099900704530PEG0898306530099890996608862A168A114A39A0A102A64A178A179A157A1974A134CLA95A153A221A92A141A142A118A119A120A121PEG1500A129A131A102A143A145A92A218A219A71A102A118A119A120A191A193A102A29A177A186A144A177A72A53A195A223A44A10A16A6A102A7A40A92A152A150A74A156A157A117PEG1500A102A159A223A76A57A10A68A69A102A159A54A146A77A78A102A179ABCDEFHGA1974A118A119A120A218A219A55A71A102A29A177A186A144A177A102A98A80A81A82A197FIG4SCANNINGELECTRONMICROSCOPICPHOTOGRAPHSOFIMPLANTSBEFOREANDA

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