单向灌流法研究姜黄素羟丙基-β-环糊精包合物的大鼠在体肠吸收
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摘要
背景:姜黄素具有良好的抗癌、抗炎等药理作用,但水溶性极低,影响了其药理活性的发挥。目的:观察姜黄素羟丙基-β-环糊精包合物及姜黄素在体肠吸收情况。方法:采用研磨法制备姜黄素羟丙基-β-环糊精包合物;检测姜黄素羟丙基-β-环糊精包合物与姜黄素的溶解度。取12只雄性SD大鼠,建立在体肠段单向灌流模型(每只大鼠选取十二指肠、空肠、回肠及结肠4个肠段),随机分2组进行药物灌流,实验组灌流姜黄素羟丙基-β-环糊精包合物水溶液,对照组灌流姜黄素混悬液,收集各肠段的灌流药液,采用紫外可见分光光度法测定姜黄素羟丙基-β-环糊精包合物及姜黄素在大鼠体内各肠段的吸收速率常速(K_a)和有效渗透率(P_(app))。结果与结论:姜黄素羟丙基-β-环糊精包合物在水中的溶解度较姜黄素提高了33.68倍;姜黄素羟丙基-β-环糊精包合物的吸收速率常数K_a结果为:十二指肠>回肠>空肠>结肠,有效渗透率P_(app)结果为:结肠>十二指肠>回肠>空肠,并且姜黄素羟丙基-β-环糊精包合物在大鼠各肠段的吸收较姜黄素明显提高(P <0.05);结果表明,姜黄素羟丙基-β-环糊精包合物能够明显改善姜黄素在大鼠肠内的吸收情况。
BACKGROUND: Curcumin has good anticancer and anti-inflammatory effects, but which is limited for the low solubility. OBJECTIVE: To investigate the intestinal absorption characteristics of curcumin hydroxypropyl-β-cyclodextrin and curcumin in rats. METHODS: The curcumin hydroxypropyl-β-cyclodextrin was prepared by grinding method, and the solubility of curcumin hydroxypropyl-β-cyclodextrin and curcumin was detected. Twelve male Sprague-Dawley rats were used to establish a one-way perfusion model of intestinal segment(duodenum, jejunum, ileum and colon), and randomly divided into two groups. The experimental group was given curcumin hydroxypropyl-β-cyclodextrin, and the control group was perfused with curcumin suspension. The absorption rate(K_a) and effective permeability(P_(app)) of curcumin hydroxypropyl-β-cyclodextrin and curcumin at each intestinal segment were measured by ultraviolet-visible spectrophotometry. RESULTS AND CONCLUSION: The solubility of curcumin hydroxypropyl-β-cyclodextrin in water was increased by 33.68 times compared with that of curcumin. The absorption rate constant(K_a) of curcumin hydroxypropyl-β-cyclodextrin was ranked as follows: duodenum > ileum > jejunum > colon, and the effective permeability(P_(app)) was ranked as follows: colon > duodenum > ileum > jejunum, and the absorption in the intestines was significantly higher than that of curcumin(P < 0.05). In summary, curcumin hydroxypropyl-β-cyclodextrin can obviously improve the absorption of curcumin in the intestines of rats.
BACKGROUND: Curcumin has good anticancer and anti-inflammatory effects, but which is limited for the low solubility. OBJECTIVE: To investigate the intestinal absorption characteristics of curcumin hydroxypropyl-β-cyclodextrin and curcumin in rats. METHODS: The curcumin hydroxypropyl-β-cyclodextrin was prepared by grinding method, and the solubility of curcumin hydroxypropyl-β-cyclodextrin and curcumin was detected. Twelve male Sprague-Dawley rats were used to establish a one-way perfusion model of intestinal segment(duodenum, jejunum, ileum and colon), and randomly divided into two groups. The experimental group was given curcumin hydroxypropyl-β-cyclodextrin, and the control group was perfused with curcumin suspension. The absorption rate(K_a) and effective permeability(P_(app)) of curcumin hydroxypropyl-β-cyclodextrin and curcumin at each intestinal segment were measured by ultraviolet-visible spectrophotometry. RESULTS AND CONCLUSION: The solubility of curcumin hydroxypropyl-β-cyclodextrin in water was increased by 33.68 times compared with that of curcumin. The absorption rate constant(K_a) of curcumin hydroxypropyl-β-cyclodextrin was ranked as follows: duodenum > ileum > jejunum > colon, and the effective permeability(P_(app)) was ranked as follows: colon > duodenum > ileum > jejunum, and the absorption in the intestines was significantly higher than that of curcumin(P < 0.05). In summary, curcumin hydroxypropyl-β-cyclodextrin can obviously improve the absorption of curcumin in the intestines of rats.
引文
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[31]罗见春,何丹,尹华峰,等.姜黄素磷脂复合物的药代动力学评价[J].第二军医大学学报,2014,35(7):754-757.
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[34]高振珅,王兰.姜黄素-羟丙基-β-环糊精包合物的制备及其理化性质研究[J].中国药房,2007,13(18):999-1000.
[35]周云,符旭东,毕诗涛.盐酸奈必洛尔-羟丙基-β-环糊精包合物的制备及表征[J].中国新药杂志,2018,27(8):954-959.
[2]Garrido-Armas M,Corona JC,Escobar ML,et al.Paraptosis in human glioblastoma cell line induced by curcumin.Toxicol In Vitro.2018;51:63-73.
[3]Chen M,Du ZY,Zheng X,et al.Use of curcumin in diagnosis,prevention,and treatment of Alzheimer's disease.Neural Regen Res.2018;13(4):742-752.
[4]Koo BB,Calderazzo S,Bowley BGE,et al.Long-term Effects of Curcumin in the Non-human Primate Brain.Brain Res Bull.2018;142:88-95.
[5]Jurenka JS.Anti-inflammatory properties of curcumin,a major constituent of Curcuma longa:a review of preclinical and clinical research.Altern Med Rev.2009;14:141-153.
[6]孙永,彭明利.姜黄素及其衍生物在肝脏相关疾病中防治作用的研究进展[J].药学学报,2014,49(11):1483-1490.
[7]Bai X,Oberley-Deegan RE,Bai A,et al.Curcumin enhances human macrophage control of Mycobacterium tuberculosis infection.Respirology.2016;21(5):951-957.
[8]张继芬,唐勤,莫婷,等.姜黄素磷脂载体的表征及肠吸收研究[J].中国药学杂志,2012,47(21):1736-1740.
[9]Maiti K,Mukherjee K,Gantait A,et al.Curcumin-phospholipid complex:Preparation,therapeutic evaluation and pharmacokinetic study in rats.Int J Pharm.2007;330(1-2):155-163.
[10]Lu PS,Inbaraj BS,Chen BH.Determination of oral bioavailability of curcuminoid dispersions and nanoemulsions prepared from Curcuma longa Linnaeus.J Sci Food Agric.2018;98(1):51-63.
[11]赵会娟,刘红星,黄初升,等.姜黄色素3种主要成分的分离纯化研究进展[J].化工技术与开发,2012,41(7):41-46.
[12]闫文丽,黄兆胜,曾晓会,等.单向灌流法研究姜黄素的大鼠在体肠吸收[J].今日药学,2012,3(12):137-141.
[13]Tan Q,Wu J,Li Y,et al.A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities:molecular characteristics,computer modeling and in vivo pharmacokinetics.Nanotechnology.2013;24(3):035102.
[14]Hu J,Chen D,Jiang R,et al.Improved absorption and in vivo kinetic characteristics of nanoemulsions containing evodiamine-phospholipid nanocomplex.Int J Nanomedicine.2014;9:4411-4420.
[15]Kunnumakkara AB,Bordoloi D,Padmavathi G,et al.Curcumin,the golden nutraceutical:Multitargetingfor multiple chronic diseases.Br J Pharmacol.2017;174(11):1325-1348.
[16]Andrew R,Izzo AA.Principles of pharmacological research of nutraceuticals.Br J Pharmacol.2017;174(11):1177-1194.
[17]Ganjali S,Blesso CN,Banach M,et al.Effects of curcumin on HDL functionality.Pharmacol Res.2017;119:208-218.
[18]Rahmani S,Asgary S,Askari G,et al.Treatment of Nonalcoholic Fatty Liver Disease with Curcumin:ARandomized Placebo-controlled Trial.Phytothe Res.2016;30(9):1540-1548.
[19]Banik U,Parasuraman S,Adhikary AK,et al.Curcumin:the spicy modulator of breast carcinogenesis.J Exp Clin Cancer Res.2017;36(1):98.
[20]Davatgaran-Taghipour Y,Masoomzadeh S,Farzaei MH,et al.Polyphenol nanoformulations for cancer therapy:experimental Evidence and clinicalperspective.Int JNanomedicine.2017;12:2689-2702.
[21]何瑶,徐晓玉,陈红,等.卡前列甲酯-羟丙基-β-环糊精包合物的制备和评价[J].中国新药杂志,2018,27(6):637-643.
[22]Merisko-Liversidge E,Liversidge GG,Cooper ER.Nanosizing:a Formulation Approachfor poorly-water-soluble compounds.Eur J Pharm Sci.2003;18(2):113-120.
[23]Gidwani B,Vyas A.A Comprehensive Review on Cyclodextrin-Based Carriers for Delivery of ChemotherapeuticCytotoxic Anticancer Drugs.Biomed Res Int.2015;2015:198268.
[24]邓少东,张鹏,林励,等.单向灌流法研究巴戟天低聚糖的大鼠肠吸收特性[J].中国中药杂志,2015,40(1):134-140.
[25]刘诗雨,柏希慧,董林娟,等.基于单向灌流法的葛根素羧甲基壳聚糖微球肠吸收特性研究[J].中草药,2016,47(14):2488-2491.
[26]罗轶凡,任利翔,李晓红,等.药物肠道吸收研究方法概述[J].药物评价研究,2017,40(5):706-710.
[27]邓少东,林靖然,林励,等.巴戟甲素的大鼠在体肠吸收动力学[J].中国实验方剂学杂志,2015,21(4):89-93.
[28]李万玉,晏子俊,孙立力.姜黄素固体脂质纳米粒在大鼠体肠中吸收的研究[J].食品与生物技术学报,2017,36(7):733-737.
[29]张雪,刘宏明,雷婷婷,等.吴茱萸碱羟丙基-β-环糊精包合物大鼠在体肠吸收特征[J].第二军医大学学报,2016,11(37):1387-1391.
[30]罗见春,胡雪原,吴建勇,等.姜黄素羟丙基-β-环糊精磷脂复合物在大鼠体内药代动力学研究[J].中药材,2015,38(3):572-575.
[31]罗见春,何丹,尹华峰,等.姜黄素磷脂复合物的药代动力学评价[J].第二军医大学学报,2014,35(7):754-757.
[32]徐伟良,詹怡飞,杨岚.NL-101-羟丙基倍他环糊精包合物的制备及其特性研究[J].中国现代应用药学,2017,34(11):1568-1571.
[33]赵孝先,高玲,梁园园,等.丁苯酞-磺丁基-β-环糊精包合物的制备与表征[J].中国现代应用药学,2016,33(6):762-767.
[34]高振珅,王兰.姜黄素-羟丙基-β-环糊精包合物的制备及其理化性质研究[J].中国药房,2007,13(18):999-1000.
[35]周云,符旭东,毕诗涛.盐酸奈必洛尔-羟丙基-β-环糊精包合物的制备及表征[J].中国新药杂志,2018,27(8):954-959.