胰岛素纳米脂质体的制备及性质研究.pdfVIP

腆岛贵纳米脂质体的制备及性质研究 研究了胰岛素脂质体大鼠小肠吸收的特性，并初步验证了脂质体作为蛋白 多肤药物口服给药载体的可自漱 、肠分段实验结果表明胰岛素脂质体回肠吸 收最大，血糖最低水平为 29.73 ，空肠其次，血糖最低水平为 51.33士 11.3%，脂质体在十二指肠无促进吸收的作用。肠壁药物含f的测定结果表明回 肠和空肠Peyer结中药物A分别为59.16士68.3gIU/g,231.82132.78}LIU/g;而 空肠和回肠中非Peyer结中的药物量分别为5.42415.815}IU/g,4.378士 3.206}LIU/g，可见Peyer结中药物ti比非Peyer结中的药物f大(p0.01)，初步 验证了脂质体经小肠Peyer区吸收.胰岛素脂质体小肠吸收程度同脂质体粒径密 切相关，吸收f随脂质体粒径减小而增加，当粒径减小到0.45gm以下时，降血 糖效果明显增加。对胰岛素脂质体结构进行改进，结果表明以HPMCP包裹胰岛 素脂质体有利于脂质体更好的吸嵘丫 丫 关键词:胰岛、乡口服、 理化性质、结构、HPLC分析方法、 月终件制备、 荧光分光光度法、酶降解作用、小肠吸收、药效学 Abstract Oraldurgdeliverysystemmaybethemostconvenientmethodforchronic disease.Fortheinsulin-dependentdiabeticpatients,insulinisthepreferredmedicine Polypeptideandproteindrugs,representedbyinsulin,havethreedifficultiesneedto overcomewhendeliveredorally:(1)thedegradationinthegastrointestinaltract妙 thepHandtheproteinase;(2)thepoorabsorptionpropertiesofmacro-moleculesin theintestinaltract;(3)thefist-passeffectofliver.Ascarrier,lecithinvesicleis compatiblewiththeintestinalmucosa.Afteroraladministration,liposomecanhelp thedrugresistthegastrointestinalcircumstanceandthedegradationbytheproteinase. Theobjectiveofthisresearchistoprepareinsulinlecithinvesicleswithhigh encapsulation.ratioandevaluatethepossibilityofthevesiclesasoraldelivery carriersofpolypeptdeandproteindurgsthroughtheexperimentinvivoandinvitro. Thereversephaseevaporationmethodwasusedtoprepareinsulin namo-liposomesandtheformulationandthepreparationtechnicsofinsulin liposomeswereoptimizedbytheuniformdesign.Furthermore,weinvestigatedthe factorsinfluencingthephysicochemicalpropertiesofthevesicles.Insulincontent wasdetectedbyHPLCmethodtheencapsulationratioofinsulinliposomeswas determinedbycolumnchromatography.Thecontentwasl.llmg/mlandthe encapsulationratiowas81.28%.Thephysicochemicalpropertiesoftheve