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1、第14卷第11期中国实验方剂学杂志Vol.14,No.112008年11月ChineseJournalofExperimentalTraditionalMedicalFormulaeNov.,2008水蛭素鼻腔给药的影响因素研究132111葛卫红,郭建友,韩玉环,石森林,陈立兵(11浙江中医药大学,浙江杭州310053;21中国科学院心理研究所,北京100101)[摘要]目的:探讨蛋白多肽类中药水蛭素的经鼻吸收特性及其影响因素。方法:用离体蟾蜍上颚黏膜模型,评价水蛭素的鼻纤毛毒性;采用Valia2Chien水平扩散池实验与在体大鼠鼻腔灌流实验,观察水
2、蛭素鼻腔给药的吸收特性以及药物浓度、pH值等因素对吸收的影响。结果:Valia2Chien水平扩散池实验和在体大鼠鼻腔灌流实验显示水蛭素能够透过鼻黏膜吸收;介质pH值、药物浓度等因素均能影响水蛭素的吸收,但水蛭素的浓度与渗透系数、吸收速度间线性关系不明显,水蛭素浓度为016-1mg·mL时,鼻黏膜吸收较好。结论:水蛭素对离体蟾蜍上颚黏膜纤毛影响较小,并且能透过鼻黏膜吸收;药物的浓度和介质的pH值对鼻黏膜的吸收均有影响。[关键词]水蛭素;鼻黏膜吸收;渗透系数;吸收速度常数;纤毛毒性[中图分类号]R28515[文献标识码]B[文章编号]100529903
3、(2008)1120037205StudiesonFactorsofNasalAbsorptionofHirudin132111GEWei2hong,GUOJian2you,HANYu2huan,SHISen2lin,CHENLi2bing(11ZhejiangUniversityofTraditionalChineseMedicine,Hangzhou310053,China;21InstituteofPsychology,ChineseAcademyofSciences,Beijing100101,China)[Abstract]Objectiv
4、e:Toinvestigatetheabsorptioncharacteristicandtheinfluencingfactorsonabsorptionofproteinandpeptidefromnaturalhirudinadministeredbynasalmucosa.Method:Thetoxicityofhirudintothenasalciliawastestedbytheexvivobufopalatemodel.Theabsorptioncharactersofnaturalhirudinaswellastheconcentra
5、tionsofnaturalhirudinandpHvaluesofmediumwereevaluatedbytheexperimentsbasedonValia2Chieninfiltrationpoolmethodandbytheinvivoperfusionexperimentsinrats.Result:TheexperimentsbasedonValia2Chieninfiltrationpoolmethodandtheinvivoperfusiontestsinratsindicatedthatthenaturalhirudinwaswe
6、llabsorbedpernasalmucousmembranefrompigsandrats.ItalsoindicatedthatboththeconcentrationsofhirudinandthepHvaluesofthemediuminfluencedtheabsorptionofhirudin.Thoughtheconcentrationofhirudinhasnoobviouslinearrelationshipwithosmoticcoefficientorrateofabsorptionofhirudinpernasalmucou
7、smembrane,itshowedthatthebestabsorptionconcentrationis016mg·-1mL1Conclusion:Hirudinhaslowciliatoxicity;itcanbewellabsorbedpernosemucousmembrane.BothoftheconcentrationsofnaturalhirudinandpHvaluesofthemediuminfluencetheabsorptioncharacteristicofhirudin.[Keywords]hirudin;nasalabso
8、rption;osmoticcoefficient;rateconstantofabsorption;cil
