【摘要】：目的:采用具有良好的生物相容性、自身降解性、無(wú)刺激性、緩釋性的天然高分子材料白及膠作為藥物載體,制備多西紫杉醇白及膠,并初步研究其腹腔注射給藥的抗腫瘤作用。方法:1、取適量中藥飲片白及低溫干燥,采用水提醇沉法獲得白及粗多糖,運(yùn)用硫酸-蒽醌法測(cè)定其中的粗多糖含量,將干燥的白及多糖溶于純水,并采用物理方法制備負(fù)載多西紫杉醇的白及膠。通過(guò)掃描電鏡觀察白及膠中多西紫杉醇的分布情況,并進(jìn)行體外釋放實(shí)驗(yàn)。2、建立荷小鼠肝癌H22腹水模型,造模24小時(shí)后隨機(jī)分為3組,即生理鹽水對(duì)照組、多西紫杉醇注射液組、多西紫杉醇白及膠組,每組5只;其中多西紫杉醇注射液組和多西紫杉醇白及膠組分別予多西紫杉醇10mg/kg劑量腹腔注射給藥,生理鹽水對(duì)照組給予等體積生理鹽水腹腔注射給藥,共給藥4次,給藥間隔72小時(shí),期間觀察小鼠的一般情況,于用藥后第15天后處死小鼠,收集腹水,計(jì)算腹水量,觀察腹腔轉(zhuǎn)移的情況,取多西紫杉醇白及膠組小鼠的重要臟器,石蠟包埋切片行HE染色后觀察各臟器組織損傷情況。結(jié)果:1、所提取的白及粗多糖中粗多糖含量為67.26%,掃描電鏡發(fā)現(xiàn)多西紫杉醇白及膠中多西紫杉醇分布較均勻,體外釋放實(shí)驗(yàn)表明多西紫杉醇白及膠呈緩慢釋放過(guò)程,其在150h后約釋放45%多西紫杉醇;2、在給藥后第10天,生理鹽水對(duì)照組測(cè)量小鼠體重,較多西紫杉醇注射液組及多西紫杉醇白及膠組明顯增加(P0.05);多西紫杉醇白及膠組較生理鹽水對(duì)照組比較,腹水量明顯減少(P0.05);同時(shí)肉眼觀察各組小鼠腸系膜上的癌結(jié)節(jié),多西紫杉醇白及膠組較生理鹽水對(duì)照組及多西紫杉醇注射液組減少;多西紫杉醇白及膠組小鼠的心肝脾肺腎HE染色切片電子顯微鏡下觀察后未見(jiàn)明顯組織損傷。結(jié)論:負(fù)載多西紫杉醇的白及膠制備簡(jiǎn)便,藥物分布較均勻,并具有一定的緩釋性。腹腔注射給藥顯示出具有一定的體內(nèi)抗腫瘤效果,值得進(jìn)一步研究。
[Abstract]:Objective: to prepare polycedar alcohol white and gum with good biocompatibility, self-degradability, non-irritant and slow-release natural macromolecule material white and gum as drug carrier. The antineoplastic effect of intraperitoneal injection was also studied. Methods: 1, the crude polysaccharide was obtained by water extraction and alcohol precipitation method, and the content of crude polysaccharide was determined by sulfuric acid-anthraquinone method, and the dried white and polysaccharide were dissolved in pure water, the dried white and polysaccharide were dissolved in pure water, and the content of crude polysaccharide was determined by sulfuric acid-anthraquinone method. The white and adhesive loaded with docetaxel were prepared by physical method. The distribution of docetaxel in white and jelly was observed by scanning electron microscope (SEM), and the release experiment in vitro was carried out. (2) the ascites model of mice bearing hepatoma H22 was established and divided into three groups at random 24 hours after establishment of the model, namely, saline control group. Docetaxel injection group, docetaxel white and glue group, 5 rats in each group; Among them, docetaxel injection group and docetaxel white group and gel group were injected intraperitoneally with docetaxel 10mg/kg, and normal saline control group were injected intraperitoneally with equal volume saline for 4 times, and the dose of docetaxel injection group and doxorubicin group were 4 times. The mice were killed on the 15th day after administration, the ascites was collected, the ascites volume was calculated, the peritoneal metastasis was observed, and the important organs of the mice in the doxorubicin group were taken from the mice treated with doxorubicin and gum. Paraffin embedded sections were stained with HE to observe the injury of each organ. The results were as follows: 1. The content of crude polysaccharide was 67.26%. SEM showed that the distribution of docetaxel in the white and gum of Taxodium dosicae was more uniform. The in vitro release test showed that the white and gum of Taxodium dosiliensis showed slow release process. About 45% docetaxel was released after 150 h. 2. On the 10th day after administration, the body weight of mice in the saline control group was significantly higher than that in the docetaxel injection group and docetaxel white and colloid groups (P0.05). Compared with the saline control group, the volume of ascites in the doxorubicin group and the colloid group decreased significantly (P0.05). At the same time, the tumor nodules on mesentery of mice in each group were observed by naked eye, the number of doxorubicin white and colloid group was lower than that of normal saline control group and docetaxel injection group. No obvious tissue damage was observed under electron microscope in the HE stained sections of heart, liver, spleen, lung and kidney of mice treated with doxorubicin and doxorubicin. Conclusion: the preparation of docetaxel-loaded white and gum is simple, the drug distribution is uniform, and it has a certain slow-release. Intraperitoneal injection showed a certain anti-tumor effect in vivo, which is worthy of further study.
【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R943;R96

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