姜黄素超微粉体的制备及生物活性评价

发布时间：2018-01-04 22:24

本文关键词：姜黄素超微粉体的制备及生物活性评价　出处：《中南林业科技大学》2015年硕士论文　论文类型：学位论文

【摘要】：姜黄素是从姜科姜黄属植物根茎中提取出来的一种天然色素,具有抗病毒、抗菌、抗肿瘤、抗炎、抗氧化、降血脂等有广泛的药理活性。但姜黄素本身难溶于水,其水溶液在中性至碱性条件下不稳定,代谢过快,极大地限制了其生物活性。因此,有必要增加姜黄素在水中的溶解度、提高其体外溶出速率。国内外学者研究并改进了多种姜黄素的新剂型,减小姜黄素颗粒的粒径是实现上述目的技术手段之一。本论文采用高压均质技术和超临界二氧化碳反溶剂技术制备了姜黄素超微粉体,优化了姜黄素超微粉体的制备工艺；对姜黄素超微粉体进行了理化性质、化学结构、体外溶出度测试与表征,并开展了姜黄素超微粉体的体外抗肿瘤活性研究。(1)建立姜黄素含量分析方法采用高效液相色谱分析姜黄素含量,方法学考察结果表明：姜黄素在浓度范围1～60μg/ml线性关系良好,含量测定方法的日内和日间精密度、稳定性、以及回收率均符合方法学考察的要求。(2)高压均质法制备姜黄素超微粉体采用高压均质法制备姜黄素纳米混悬剂,优化了姜黄素超微粉体(粉体A)的制备工艺；结果表明,均值压力1000 bar,循环次数30次,姜黄素纳米混悬剂的平均粒径为(171.0±8.56)nm,一致性系数为(0.6940±0.05)；冻干保护剂适宜工艺条件为：甘露醇浓度为4%(W/W),加入方式为内加法,预冻温度为-20℃,预冻时间为24h。IR,UV, XRD和HPLC显示,姜黄素超微粉体化学结构未见改变,与姜黄素原粉相比,姜黄素超微粉体在水中的溶解度有大幅度提高；姜黄素超微粉体外溶出速率也明显提高,120 min时,溶出度已达80%。高压均质法是一种适用于姜黄素超微粉体的制备方法。(3)超临界二氧化碳反溶剂制备姜黄素超微粉体采用超临界二氧化碳反溶剂法制备姜黄素超微粉体(粉体B),以丙酮为溶剂,以微粒粒径为指标,考察了结晶压力,结晶温度,溶液流速,溶液浓度等工艺参数。确定适宜工艺条件为：结晶压力30 Mpa,结晶温度53℃,溶液浓度12.5mg/mL,溶液流速9 mL/min,所制备的姜黄素颗粒平均粒径为450～550 nm。IR,UV表明姜黄素超微粉体化学结构未见改变；XRD表明姜黄素超微粉体结晶化程度低于姜黄素原粉,结晶程度越低,水溶性越好；TG/DTG和DSC表明超微化后姜黄素稳定性没有改变,但姜黄素超微粉体熔化所需能量低于姜黄素原粉。水溶性实验表明,姜黄素超微粉体在水中的溶解度随颗粒粒径的减小而增大。(4)姜黄素超微粉体体外抗肿瘤活性研究采用MTT方法,研究了姜黄素超微粉体(粉体A和粉体B)对HepG2、HCT116两种细胞生长的抑制作用。结果显示：HepG2、HCT116细胞生长明显受抑制,随着姜黄素超微粉体浓度的增加其抑制作用增强。姜黄素超微粉体粉体A和粉体B以及姜黄素原粉对HepG2细胞的IC50值分别为11.95μg/mL、12.76μg/mL和24.14μg/mL;对HCT116的IC50值分别为10.87μg/mL、11.24μg/mL和24.14μg/mL。研究结果表明减小姜黄素颗粒的粒径,能增强姜黄素的体外抗肿瘤活性,因而也可进一步提高其生物利用度。
[Abstract]:Curcumin is a kind of natural pigment extracted from Curcuma in antiviral, antibacterial, antitumor, anti-inflammatory, antioxidant, hypolipidemic and has extensive pharmacological activity. But curcumin is insoluble in water, its water solution is not stable in neutral to alkaline conditions, rapid metabolism, great to limit its biological activity. Therefore, it is necessary to increase the solubility of curcumin, improve the dissolution rate. Domestic and foreign scholars and many new forms of curcumin improved, curcumin reduced particle size is one of the means of achieving these goals. In this paper, and the supercritical carbon dioxide anti solvent preparation technology the curcumin ultrafine powder by high pressure homogenization technology, optimize the preparation process of curcumin ultrafine powder; ultrafine powder of curcumin on physicochemical properties, chemical structure, test and characterization of in vitro dissolution, and The superfine powder of curcumin antitumor activity in vitro. (1) analysis method was established by HPLC analysis of the content of curcumin content of curcumin, the methodological study results show that curcumin in the concentration range of 1 ~ 60 g/ml good linear relationship, a method for the determination of the intra day and inter day precision, stability and recovery. Rate are consistent with the methodological study. (2) high pressure homogenization preparation of curcumin ultrafine powders prepared by the high pressure homogenization method of curcumin nano suspension, optimization of the curcumin superfine powder (A powder) in the preparation process; the results show that the mean pressure of 1000 bar, 30 cycles, the average particle of curcumin nanoparticles suspension of the diameter of (171 + 8.56) nm, consistency coefficient (0.6940 + 0.05); cryoprotector suitable conditions: the mannitol concentration was 4% (W/W), joined the way in law, pre freezing temperature of -20, pre Freezing time is 24h.IR, UV, XRD and HPLC showed that curcumin ultrafine powder chemical structure was not changed, compared with the original powder of curcumin, curcumin ultrafine powder has greatly improved solubility in water; rate also obviously improve the dissolution of curcumin powder in vitro, 120 min, dissolution rate has reached 80%. high pressure homogenization method is a kind of method is suitable for preparation of curcumin ultrafine powder. (3) carbon dioxide supercritical anti solvent preparation of supercritical carbon dioxide anti solvent preparation of curcumin ultrafine powder using curcumin superfine powder (B powder), using acetone as the solvent, with the particle size as indexes, the influences of crystallization pressure, crystallization temperature, solution flow rate, solution concentration and other parameters. To determine the optimum conditions for crystallization pressure of 30 Mpa, the crystallization temperature of 53 DEG C, the concentration of 12.5mg/mL solution, the flow rate of 9 mL/min, the particles prepared by curcumin with an average diameter of 450 ~ 550 nm.IR UV, show that curcumin ultrafine powder did not alter the chemical structure of XRD ultrafine powder; curcumin crystallization degree is lower than that of curcumin powder, the crystallization degree is low, the water soluble TG/DTG and DSC showed better; after ultramicronization stability of curcumin has not changed, but the curcumin ultrafine powder required for melting energy less than the original powder water soluble curcumin. Experiments show that curcumin ultrafine powder increases the solubility in water increases with the decrease of particle size. (4) using curcumin superfine powder in vitro antitumor activity of MTT and curcumin superfine powder (A powder and B powder) on HepG2 growth inhibition effect of HCT116 two cells. The results showed that HepG2, HCT116 cell growth was significantly inhibited, with the increase of the concentration of curcumin powder is enhanced. The inhibitory effect of curcumin IC50 superfine powder, A powder and B powder and powder of curcumin on HepG2 cells Values were 11.95 g/mL, 12.76 g/mL and 24.14 g/mL; the HCT116 IC50 values were 10.87 g/mL, 11.24 g/mL and 24.14 g/mL. the results of the study show that curcumin decreased the particle size, can enhance the antitumor activity of curcumin in vitro, which can further improve its bioavailability.

【学位授予单位】：中南林业科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TQ28;TB383.3

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