本文選題：姜黃素 + 固體分散體��； 參考：《華北理工大學》2015年碩士論文

【摘要】：目的本研究以可溶性的高分子材料聚乙烯吡咯烷酮(PVP k30)為載體將姜黃素制成固體分散體,用以提高姜黃素的生物利用度。探討姜黃素固體分散體對鎘致雄性生殖毒性的干預作用,對鎘引起的雄性生殖毒性的治療提供新的線索和思路。方法1姜黃素固體分散體的制備:以水溶性載體材料PVP k30為載體,分別制備1:2,1:4,1:6三種比例的姜黃素固體分散體,通過溶解度測定和體外溶出度測定篩選出最佳比例。用示差掃描量熱分析(DSC)進行驗證。2姜黃素固體分散體對鎘致雄性大鼠生殖毒性的干預研究:健康的SPF級雄性SD大鼠(體重180-200g)40只,經(jīng)過一周的適應性飼養(yǎng),按照體重隨機分為5組,分別為空白對照組,染鎘組,姜黃素組(60 mg/kg),姜黃素固體分散體低劑量組(300 mg/kg)和姜黃素固體分散體高劑量組(450 mg/kg),除空白組外其余各組腹腔注射氯化鎘2.0mg/kg,2天/次,染毒6次,空白對照組給予等體積的0.9%的生理鹽水。染毒的同時灌胃給藥,空白對照組和染鎘組用等體積0.9%生理鹽水灌胃。每天一次,連續(xù)給藥6周。檢測:組織中鎘含量,附睪精子計數(shù),睪丸組織超氧化物歧化酶(SOD)、半胱氨酸天冬氨酸蛋白酶(caspase-3)的活力和丙二醛(MDA)的水平,蘇木素-伊紅(HE)染色法觀察睪丸組織病理切片。數(shù)據(jù)處理:采用統(tǒng)計學軟件SPSS Statistics V17.0,數(shù)據(jù)結果均以(sx±)表示,整體組間為單因素方差分析,兩兩比較采用LSD分析,P0.05差異有統(tǒng)計學意義。結果1姜黃素制成固體分散體后,溶解度和體外溶出度明顯增加,并且姜黃素與PVP k30質(zhì)量比為1:4時增溶效果最佳。經(jīng)DSC分析證明得到了固體分散體。2姜黃素固體分散體對鎘致雄性大鼠生殖毒性的干預研究的測定結果:染鎘組大鼠精子數(shù)量、活動率和SOD活力明顯降低,精子畸形率和MDA水平、caspase-3含量升高,與空白對照組相比差異有統(tǒng)計學意義(P0.05),給藥組精子數(shù)量、活動率和SOD活力升高,精子畸形率和MDA水平、caspase-3含量降低;病理切片顯示,染鎘組睪丸生精小管被破壞,生精細胞數(shù)目減少,給藥組與之相比結構完整,高劑量的姜黃素固體分散體組更接近空白對照組。結論姜黃素具有清除自由基、抗氧化的能力,為了改善其溶解度差,生物利用度低的缺點,將其制成固體分散體。對于鎘造成的雄性大鼠的生殖毒性,如精子存活率、活動率、畸形率,睪丸的氧化損傷與細胞凋亡等方面,姜黃素固體分散體有很好的治療作用,固體分散體組的作用優(yōu)于姜黃素組,表明制成固體分散體后姜黃素在體內(nèi)的吸收增加,生物利用度得到改善,能夠更好的發(fā)揮其藥理活性。
[Abstract]:Aim in this study, curcumin was prepared into solid dispersion by using soluble polymer polyvinylpyrrolidone (PVP K 30) as carrier to improve the bioavailability of curcumin. To explore the effect of curcumin solid dispersion on male reproductive toxicity induced by cadmium and to provide new clues and ideas for the treatment of cadmium induced male reproductive toxicity. Methods (1) preparation of curcumin solid dispersion: three ratios of curcumin solid dispersion (1: 2: 1: 1: 4: 6) were prepared with water soluble carrier PVP K30 as carrier. The best proportion was obtained by solubility determination and dissolution test in vitro. The intervention of curcumin solid dispersion on cadmium induced reproductive toxicity in male rats was studied by differential scanning calorimetry (DSC). According to body weight, they were randomly divided into 5 groups: blank control group, cadmium exposed group, Curcumin group (60 mg / kg), curcumin solid dispersion (low dose group) (300 mg / kg) and curcumin solid dispersion group (high dose group) (450 mg / kg). The blank control group was given 0.9% saline of equal volume. The rats in the control group and the cadmium group were treated with 0.9% normal saline in the same volume. Once a day for 6 weeks. The contents of cadmium, the sperm count of epididymis, the activity of superoxide dismutase (SOD), caspase-3 (cysteine aspartate protease) and the level of malondialdehyde (MDA) in testis were measured. The pathological sections of testis were observed by hematoxylin and eosin (HEH) staining. Data processing: SPSS Statistics V17.0 was used, the data results were all expressed as SX 鹵), the whole group was single factor ANOVA, the difference was statistically significant by LSD analysis (P0.05). Results 1 the solubility and dissolution in vitro of curcumin were significantly increased after the preparation of solid dispersion, and the solubilization effect was the best at 1:4 when the mass ratio of curcumin to PVP K30 was 1:4. The results of DSC analysis showed that the intervention of solid dispersion .2 curcumin solid dispersion on the reproductive toxicity of cadmium induced by cadmium in male rats showed that the sperm number, motility and SOD activity of cadmium exposed rats were significantly decreased. The rate of sperm malformation and the content of caspase-3 were significantly higher than those of the blank control group (P 0.05). The sperm quantity, motility and SOD activity in the administration group were increased, while the sperm deformity rate and MDA level were decreased. The testicular seminiferous tubules were destroyed and the number of spermatogenic cells decreased in the cadmium exposed group. Compared with the control group, the structure of the spermatogenic cells in the administration group was intact, and the high dose curcumin solid dispersion group was closer to the blank control group. Conclusion curcumin has the ability of scavenging free radical and antioxidation. In order to improve its poor solubility and low bioavailability, curcumin was prepared into solid dispersion. Curcumin solid dispersion has a good therapeutic effect on cadmium induced reproductive toxicity in male rats, such as sperm survival rate, motility rate, deformity rate, oxidative injury of testis and apoptosis. The effect of solid dispersion group was better than that of curcumin group, which indicated that the absorption of curcumin in vivo was increased, the bioavailability of curcumin was improved, and the pharmacological activity of curcumin was better than that of curcumin group.
【學位授予單位】：華北理工大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R114

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