新疆紫草提取物脂质体乳膏剂的制备
|
摘要
目的:制备新疆紫草提取物脂质体(L-AEE)乳膏剂,并进行体外释放和动物皮肤用药安全性考察。方法:(1)分别采用薄膜分散法、逆相蒸发法、乙醇注入法、乙醚注入法和熔融法制备L-AEE,以脂质体的包封率、形态、粒径分布为指标,比较不同制备方法的可行性。(2)在单因素基础上,对选定方法进行正交试验设计,筛选制备L-AEE的优化处方和工艺。(3)考察优化工艺下制备的脂质体含药量、包封率、pH、形态、粒径分布及Zeta电位、表面电性、体外释放度、稳定性等质量控制指标。(4)通过离心、耐热、耐寒试验、稳定系数KE、物理外观,进行基质筛选;以累积渗透量为指标,考察乳膏剂透皮渗透性能;局部皮肤给药,观察对新西兰兔皮肤的急性毒性和刺激性,对豚鼠的过敏性反应。结果:(1)综合考察不同的制备方法,乙醇注入法制备的L-AEE各项指标较好。(2)优化处方和工艺下制得的L-AEE的平均含药量为(0.084±0.003)g.g-1;平均包封率为(81.98±2.14)%;pH为6.94±0.04;透射电镜观察L-AEE形状较规则,外形呈圆球形或椭球形的小囊泡,粒子大小均匀,多为小单室脂质体;扫描电镜观察,脂质体外部呈球形结构;用激光粒度分析仪测定脂质体的平均粒径为(297.58±6.41);ζ电位值为(-59.24±1.51) mV,ζ电位值绝对值>30 mV,体系稳定;表面电性为负。(3)L-AEE体外释放符合Higuchi线性方程;在4℃和25℃条件下贮存60 d后,组间与组内比较其平均粒径及包封率具有明显差异。(4)O/W型L-AEE乳膏剂膏体均匀、质地细腻,易于涂布;未产生急性毒性反应;一次或多次给药,对动物完整皮肤和破损皮肤均无刺激和致敏性。结论:乙醇注入法适合于制备L-AEE,该脂质体在4℃条件下保存较稳定;O/W型乳膏释药速度较W/O型快,皮肤局部应用无毒性、刺激性和过敏反应。
Objective: To prepare the Arnebia euehroma (Royle) Johnst extracts liposomes (L-AEE), evaluate the dissolution profile and safety to skin. Methods: (1) The thin film dispersion method, reverse phase evaporation vesicle method, ethanol injection-extrude method, ether injection method and melting methods were used to prepare the L-AEE, respectively, to compare the reliability of different preparing methods with the indexes of entrapment efficiency, shapes and the distribution of particle size.(2) On the bases of single factor testing , the orthogonal design was adopted to select the prepare method to optimize the technology and formulation of L-AEE.(3) Under the condition of preparing technology optimized, the indexes of quality controlling to L-AEE such as entrapment efficiency, pH value, shapes, the distribution of particle size, Zeta-potential, superficial electricity, dissolution rate and stability were observed, respectively.(4) Through the test of centrifuge, hot bearing, cool bearing and coefficient of stability(KE), physical appearance to select the base of the cream; The permeation of the cream were observed using the accumulated amount of drug as indexes through the present membrane; the acute toxicity, irritation and the allergy reaction on normal and damaged skin were tested after spread the cream on the back of rabbit or cavia cobaya that hairs were cut off. Results:(1) Compare the different methods of preparation comprehensively, the ethanol injection-extrude method was more suitable to prepare the L-AEE.(2) The parameters of L-AEE prepared under the formulation and preparation condition optimized were as follows: the average concentration of drug was (0.084±0.003)g.g-1; the average entrapment efficiency defined were (81.98%±2.14)%; the average particle size were (297.58±6.41)nm; the pH value was 6.94±0.04; the drug-loaded particles were observed with spherical shapes, uniform size, and mostly single unilateral vesicles under the transmission electric microscope; the Zeta-potential was (-59.24±1.51) mV with negative electric(.3)The L-AEE showed quite stable being stored at 4℃in refrigerator for 60 d.(4)The O/W type of formula on the L-AEE cream showed uniform in content ,fine in appearance and easy to spread, there were no any irritation, allergic and toxicity on the skin after single and multi administrated to normal and damaged skin. Conclusion: The ethanol injection-extrude method was suitable to prepare the L-AEE, it was quite stable being stored at 4℃in refrigerator; O/W cream showed far more fast release than that of W/O, it was safe and no evidence of irritation, allergic and toxicity.
Objective: To prepare the Arnebia euehroma (Royle) Johnst extracts liposomes (L-AEE), evaluate the dissolution profile and safety to skin. Methods: (1) The thin film dispersion method, reverse phase evaporation vesicle method, ethanol injection-extrude method, ether injection method and melting methods were used to prepare the L-AEE, respectively, to compare the reliability of different preparing methods with the indexes of entrapment efficiency, shapes and the distribution of particle size.(2) On the bases of single factor testing , the orthogonal design was adopted to select the prepare method to optimize the technology and formulation of L-AEE.(3) Under the condition of preparing technology optimized, the indexes of quality controlling to L-AEE such as entrapment efficiency, pH value, shapes, the distribution of particle size, Zeta-potential, superficial electricity, dissolution rate and stability were observed, respectively.(4) Through the test of centrifuge, hot bearing, cool bearing and coefficient of stability(KE), physical appearance to select the base of the cream; The permeation of the cream were observed using the accumulated amount of drug as indexes through the present membrane; the acute toxicity, irritation and the allergy reaction on normal and damaged skin were tested after spread the cream on the back of rabbit or cavia cobaya that hairs were cut off. Results:(1) Compare the different methods of preparation comprehensively, the ethanol injection-extrude method was more suitable to prepare the L-AEE.(2) The parameters of L-AEE prepared under the formulation and preparation condition optimized were as follows: the average concentration of drug was (0.084±0.003)g.g-1; the average entrapment efficiency defined were (81.98%±2.14)%; the average particle size were (297.58±6.41)nm; the pH value was 6.94±0.04; the drug-loaded particles were observed with spherical shapes, uniform size, and mostly single unilateral vesicles under the transmission electric microscope; the Zeta-potential was (-59.24±1.51) mV with negative electric(.3)The L-AEE showed quite stable being stored at 4℃in refrigerator for 60 d.(4)The O/W type of formula on the L-AEE cream showed uniform in content ,fine in appearance and easy to spread, there were no any irritation, allergic and toxicity on the skin after single and multi administrated to normal and damaged skin. Conclusion: The ethanol injection-extrude method was suitable to prepare the L-AEE, it was quite stable being stored at 4℃in refrigerator; O/W cream showed far more fast release than that of W/O, it was safe and no evidence of irritation, allergic and toxicity.
引文
[1]国家药典委员会编.中华人民共和国药典(2005版,一部)[M].北京:化学工业出版社,2005,238-239.
[2]葛锋,王晓东,王玉春.药用紫草的研究进展[J].中草药,2003,34(9):附6-7.
[3]卢贺起,丁家欣,魏雅川.紫草的实验研究进展[J].中国中医药信息杂志,1998,5(1):20-23.
[4]罗学娅,李明辉,吕莉等.紫草的药理作用与应用研究进展[J].大连大学学报,2004,25(2):80-92.
[5]黎玉红,周晓荣.新疆紫草的研究进展[J].新疆中医药,2002,20(4):75-77.
[6]黄志纾,张敏,马林等.紫草的化学成分及其药理活性研究概况[J].天然产物研究与开发,1999,12(l):73-82.
[7] Fumihiko Yoshizaki,Shuji Hisamichi,Yashikazu Kondo,et al.Studies on shikon.New furylhydroquinone derivatives,shikonofurans A,B,C,D and E from Lithospermum erythrorhizon Sieb.et Zucc.[J].Chemieal & Pharmaceutical Bull- erin ,1982,30(12):4407-4411.
[8]邵鹏飞.新疆紫草化学成分的研究[D].中国药科大学硕士学位论文,2001.
[9] I.Morimoto,T.Kishi,S.Ikegami. Naphthoquinone derivatives from Lithospermum erythrorhizon Sieb.et Zuec[J].Tetrahedron Letters,1965,(52):4737-4739.
[10] B.Bozan,K.H.C.Baser,S.Kara.Quantitative determination of naPhthaquinones of Arnebia densflora(Nordm.)Ledeb.by an improved high-performance liquid chromatographic method [J].Journal of Chromatography A,1997,782:133-136.
[11] YS.Chang,S.C.Kuo,S.H.Weng,et al.Inhibition of platelet aggregation by shikonin derivatives isolated from Arnebia euchroma[J].Journal of Medicinal Plant Research,1993,59(5):401-404.
[12]傅善林,肖培根.新疆软紫草中萘醌色素的研究[J].中草药,1986,17(10):2.
[13] Bai G .Chem Res Chinese Universities.1994,10(3):263.
[14] R.K.Khajuria,S.M.Jain. Two bew naphthoquinones from the roots of Onosoma hispidumt[J].Indian Journal of Chemistry,1993,32B:390-391.
[15] X.S.Yao,YE bizuka,H.Noguchi,et al.Sanikawa Biologieally active constituents of Arnebia euchroma:structure of arnebinol,an monoterpenylenzenoid with inhibitory activity on prostaglandin biosynthesis[J].Chemical and pharmaceutical Bulletin,1991,39(11):2956-2961.
[16]严松柏,谈献和,胡玉涛.紫草的研究进展[J].时珍国医国药,2003,14(2):103-105.
[17]吕秀芬,田景奎,周丽华.中药有效成分及其作用简述[J].时珍国药研究,1997,8(3):281.
[18]赵利.紫草的药理研究进展[J].武警医学,1997,8(2):115.
[19] [19]李忠良.紫草中紫草素的含量测定[J].药物分析杂志,1986,6(1):41.
[20] [20]张敏,金永清,郭兰建等.紫草的鉴别及其有效成分羟基萘醌色素类含量测定[J].中草药,1989,20(10):17-18.
[21]阎江丽,王建林.紫草中天然色素物化特性的研究[J].精细化工,1994,11(6):57.
[22]杨晓笛,卢锋,黄美充等.中药紫草有效成分的提取[J].汕头大学学报(自然科学版),2002,17(4):67-70.
[23]李惠兰,秦剑,何洪静等.滇紫草、新疆紫草和露蕊滇紫草提取物药效学研究[J].中国民族民间医药杂志,2002,12(3):174-176.
[24] Fukui H,Hasan A F M F,Kyo M.Formation and secretion of a unique quinone by hairy root cultures of Lithospermum erythrorhizon[J].Phytochemistry,1999,51(4): 511-515.
[25] Yamamoto H,Inouea K,Yazakib K.Caffeic acid oligomers in Lithospermum erythrorhizon cell suspension cultures[J].Phytochemistry,2000,53(6):651-657.
[26]孙培杰.紫草的药理作用与临床应用研究进展[J].中医药信息,2002,l9(4):19.
[27]沈映君.中药药理学[M].北京:人民卫生出版社,2O00,289-292.
[28] Li HY,Luo SR ,Zhou TH.Metabolism of Shikonin in Rats[J].Journal of Chinese Pharmaceutical Sciences,1999,8(3):148-151.
[29]辛玲.硬紫草质量评价研究[D].黑龙江中医药大学硕士学位论文,2008.
[30]张秀娟,刘佰华,穆坤等.紫草及其提取物生物学活性研究进展[J].中国微生态学杂志,2007,19(6):579.
[31]魏林,陈祥明,秦光.紫草油治疗放射性皮肤溃疡愈合观察[J].中国临床康复,2004,8(5):30.
[32]田世禹,于甬华,陈延条等.紫草等中药油膏治疗急性放射性皮肤损伤的疗效观察[J].肿瘤防治杂志,2002,9(4):25.
[33] Kiyoshi K,Malgoriats S,Howard L.percutaneous absorption:a single-layer model[J]. J Phrem Sci,1993,82(5):450.
[34] Korting HC.Eur J Clin Pharmaeol,1990,39:349.
[35] Schhreier H,Bouwstra J.Liposomes and niosomes as topical drug carrier:dermal and transdermal drug delivery[J]. J Controlled Release,1994,30:l-13.
[36]李国锋,侯连兵,曾抗.维甲酸脂质体的制备与临床应用[J].中国药学杂志,1998,33(2):121-122.
[37]何文,吴宏霞,蔡鸿生等.8-甲氧补骨脂素脂质体凝胶的研制[J].中国医院药学杂志,2004,24(1):3.
[38] Chung-SJ.Future drug delivery researeh in South Korea[J]. J-Controlled-Release,1999,62(l2):73-9.
[39] Michelson AM,Stadtman E,Boon P,et al.Decreased skin superoxide dismutase activity by a single exposure of ultraviolet radiation was reduced by liposomal superoxide petreatment[J].J Dermatol,1996,96(13):1376-1383.
[40] Plessis JD,Weiner N,Muller PG.The influence of in vivo treatment of skin with liposomes on the topical absorption of a hydrophilic and a hydrophobic drug in vitro[J].Int J Phann,1994,103(1):1-5.
[41] Lasch J,Wohlrab W.Liposome-bound cortisol:a new approach to cutaneous therapy[J].Biomed Biochim Acta,1996:45:1295-1299.
[42]张越珍,林军.天然药物脂质体制备研究进展[J].中国药房,2007,18(21):1671.
[43]张灵芝.脂质体制备及其在生物医学中的应用[M].北京医科大学、中国协和医科大学联合出版社,1998,101.
[44] Sharata HH. Int J Dermatol,1996,35(11):761.
[45] Roding J,Ghyczy M,Control of skin humidity with liposomes and stabilization of skin care oils and lipophilic active substances with liposomes [J].SOFW,1991,10:372.
[46] Mezei M,Gulasekharam V.Liposomes—a selective drug delivery system for the topical route of administration: I.Lotion dosage form[J].Life Sci,1980, 26:473-489.
[47]张路,简江波,盛燕等.马钱子碱脂质体的大鼠离体透皮性能和兔皮肤刺激性研究[J].中国医药工业杂志,2006,37(3):172.
[48]王欢,陆彬,杨红.咪喹莫特脂质体与乳膏体外经皮扩散行为的比较[J].中国医药工业杂志,2003,34(2):73-75.
[49]白铭,张恒术,王昆等.辣椒素脂质体在体外瘢痕组织中透皮吸收的研究[J].沈阳药科大学学报,2004,21(1):8-10.
[50] Row TC, Okamoto H, Weiner ND, et al. Mechanisms of topical delivery of liposomally entrapped drugs[J].Skin Pharmacol,1994,7:346-352.
[51] Gehring W, Klein M, Gloor M. Liposome Dermaties,1992,315.
[52] Sciliano AA, Martin GP, Montenegro L, et al. Procedure for preparation of liposomes with large interal aqueous space and high capture by reverse-phase evaporation[J].Adv Drug Delivery Rev,1996,18(3):303-308.
[53]吴宏霞,何文,蔡鸿生.脂质体作为皮肤局部给药载体的研究进展[J].中国现代应用药学杂志,2004,21(2):115.
[54]范芳芳,刘泽蒲,陈文等.紫外分光光度法测定新疆紫草中总萘醌的含量[J].石河子大学学报(自然科学版) ,2004,22 (5):425-426.
[55]杨秀芳.紫草提取工艺的优化[J].陕西科技大学学报,2004,22(4):5-37.
[56]马瑛,王嗣岑,黄猛.HPLC测定紫草中紫草素含量[J].中国药学杂志,2000,35 (2):98.
[57]谢秀琼,邱明丰.对制剂中紫草成分和提取工艺的探讨[J].中国药房,1997,8(2):60-61.
[58]李立荣,崔志高,肖润禾等.对紫草中紫草色素的初步研究[J].湖南中医学院学报,2000,20(2):25-27.
[59]赵雪梅,王桂玲,费洪荣等.紫草有效成分的提取及其抗炎作用研究[J].中药药理与临床2008,24(4):36-38.
[60]杨秀芳.正交实验法优选紫草的提取工艺[J].中成药,2005,27(3):351-353.
[61]吴学渊,刘萍.正交试验设计优选紫草的醇提工艺[J].中国医院用药评价与分析,2008,8(10):750-752.
[62]熊利容.白藜芦醇苷脂质体的制备及其药代动力学的研究[D].湖北中医学院硕士学位论文,2007.
[63]黄亚东,项琪,张宏波等.碱性成纤维细胞生长因子脂质体的制备和评价[J].中国药学杂志,2008,43(13):992-997.
[64]沃兴德,洪行球,高承贤等.姜黄素长期毒性试验[J].浙江中医学院学报,2000,24(1):61-65.
[65]张学农,孙殿甲,李观海.去氢骆驼蓬碱脂质体的研究[J].中国医药工业杂志,1994,25(10):441-445.
[66]吴明星,利华明,李绍珍等.骆驼蓬总碱及其脂质体对兔晶状体上皮细胞的抑制作用[J].眼科研究,1999,27(4):275.
[67]刘衍兴,郭辉.小糪碱及其脂质体降血搪作用实验研究[J].基层中药杂志,1999,13(1):18-19.
[68]薛玉英,翁帼英,何俊峰等.口服硫酸氢黄连素脂质体的研制[J].中国中药杂志,1995,20(12):730.
[69]穆筱梅,梁世强.脂质体的制备方法及其研究进展[J].时珍国医国药,2008,19(7):1784-1786.
[70]许汉林,孙芸,邵继征等.姜黄素脂质体的制备及理化性质考察[J].中国医院药学杂志,2007,27(10):1363-1365.
[71]李淑斌,刘丹,宁红等.紫杉醇固体脂质纳米粒包封率的测定[J].中国药学杂志,2008,43(21):1665-1668.
[72]国家药典委员会编.中华人民共和国药典(2005版,二部)[M].北京:化学工业出版社,2005,附录181.
[73]黄红兵,刘韬,徐月红等.多西紫杉醇脂质体制备工艺及处方优化研究[J].中国药学杂志,2007,42(24):1872-1876.
[74]张鹤鸣,穆成林.酮洛芬脂质体的制备和质量评价[J].中国医院药学杂志, 2007,27(8):1161-1163.
[75]徐晖,李英剑,严志等.黄体酮缓释凝胶的体外释放性质[J].中国药剂学杂志,2003,l(l):6-9.
[76]宋金春,陈佳丽,刘薇芝.葛根素前体脂质体的质量考察[J].中国医院药学杂志,2007,27(9):1244-1246.
[77]彭海龙,雷志强,刘燕燕等,槐定碱脂质体的制备及理化性质研究[J].中国医院药学杂志,2009,29(1):32-35.
[78]吕长江.愈肤灵乳膏制备及质量控制[J].浙江中西医结合杂志,2006,16(2):126.
[79]邢建国,孙殿甲,管慧等.盐酸去氢骆驼蓬碱软膏的处方筛选[J].中成药,2001,23(5):316-318.
[80]刘可春,刘昌衡,王希敏等.辣椒碱软膏基质及其配方的优选试验研究[J].2004,17(2):33-36.
[81]张学农,孙殿甲,周颖.利湿平软膏的处方筛选[J].中成药,1998,20(1):8-10.
[82]马萍,辛艳茹,杨京燕等.离心分光光度法测定乳剂稳定性[J].药学实践杂志,2001,19(l):23.
[83]向俊霖,张莉,王晓辉等.尼莫地平脂质体的制备及体外透皮研究[J].中国药房,2009,20(1):36-38.
[84]杨晓春,张强,吴镭.目前我国透皮给药系统研究的基本思路[J].中国新药杂志,2001,10(5):321-324.
[85]李琦,王凤山,凌沛学等.以玻璃酸钠为媒介对布洛芬体外释放及透皮吸收的影响[J].中国医院药学杂志,2007,27(9):1235-1238.
[86]朱亚丽,盛国荣.复方咪康吟乳膏动物实验研究[J].海峡药学,2005,17(6):59-60.
[87]刘丽春,腾宝霞,苏晓洁等.复方维甲酸霜的皮肤急性毒性、皮肤变态反应及刺激性实验研究[J].兰州大学学报(医学版),2005,31(3):61-62.
[88]徐淑云,卞如镰,陈修.药理实验方法学[M].北京人民卫生出版社, 2002,1537-1539.
[89]姜华.芦荟鼻按软膏药效学及毒理学实验研究[J].甘肃中医,2003,16(l):40-41.
[90]薛育梅.氯地霜动物实验研究[J].黑龙江医药,2004,17(6):420-421.
[91]李淑斌,刘丹,宁红等.紫杉醇固体脂质纳米粒包封率的测定[J].中国药学杂志,2008,43(21):1665-1668.
[1]葛锋,王晓东,王玉春.药用紫草的研究进展[J].中草药,2003,34(9):附6-10.
[2]初雨,潘晓玲.新疆药用资源植物及其开发利用现状[J].中国野生植物资源,20(1):21-23.
[3]史建玲,李琦,张春雨.新疆博尔塔拉蒙古自治州主产药材简介[J].新疆中医药,2002,20(4):43-44.
[4] [4]冯缨,严成,尹林克.新疆植物特有种及其分布[J].西北物学报,2003,23(2):263-273.
[5]黄志纾,张敏,马林等.紫草的化学成分及其药理活性研究概况[J].天然产物研究与开发,2000,12(1):72-82.
[6]蒋英丽,宋今丹.新疆紫草素诱导人大肠癌细胞的凋亡[J].癌症,2001,20 (12):1355-1358.
[7] Singh F,Gao D,Lebwohl MG,et a1.Shikonin modulates cell proliferation by inhibiting epidermal growth factor receptor signaling in human epidermoid carcinoma cells[J].Cancer Lettr,2003,200(2):115-121.
[8] Wu Z,Wu L,Li L,et a1.p53-Mediated cell cycle arrest and apoptosis induced by shikonin via a caspase-9-dependent mechanism in human malignant melanoma A375-S2 cells[J].J Pharmacol Sci,2004,94(2):166-176.
[9]张阳,王英丽,齐红等.新疆紫草素抗肝癌的实验研究[J].实用肿瘤学杂志,2006,20(4):294-295.
[10]徐贵颖,郭敏,王英丽.新疆紫草素对荷H22肝癌小鼠抗肿瘤的实验性研究[J].中华医学全科杂志,2004,5(3):22-24.
[11]林江,韩福刚,王开正等.新疆紫草素对肿瘤细胞生长抑制作用的研究[J].泸州医学院学报,2003,26(2):102-105.
[12] Gaddipati J P, Mani H,Shefali,et a1.Inhibition of growth and regulation of IGFs and VEGF in human prostate cancer cell lines by shikonin analogue 93/637(SA)[J].Anticancer Res,2000,20(4):2547-2552.
[13] Hashimoto S,Xu M,M asuda Y,et a1.beta-hydroxyisovalerylshikonin inhibits the cell growth of various cancer cell lines and induces apoptosis in leukemia HL-60 cells through a mechanism different from those of Fas and etoposide[J].J Biochem(Tokyo),1999,125(1):17-23.
[14]胡艳萍,王骏业.紫草素增加小鼠肝癌和Lewis肺癌放射治疗效应的初步研究[J].肿瘤防治研究,1991,18(2):71-73.
[15]王薇,李萍萍.紫草提取物对MCF-7细胞及小鼠雌孕激素水平的影响[J].中国中药杂志,2003,28(11):1062-1067.
[16]刘梅青.不同剂量紫草醇提取物对表皮细胞过度增殖的实验研究[J].临床医药实践杂志,2003,12(7):485-487.
[17]吴晓霞,周武庆.紫草素对角质形成细胞株增殖的抑制及凋亡的作用[J].中国麻风皮肤病杂志,2003,19(6):563-566.
[18]买尔旦·马合木提,刘燕,古丽仙·胡加等.新疆紫草提取物对小鼠急性酒精性肝损伤的保护作用[J].中国药物与临床,2007,7(4):284-286.
[19]刘燕,买尔旦·马合木提,尼加提·热合木.新疆紫草提取物对小鼠免疫性肝损伤的保护作用[J].新疆医科大学学报,2006,29(6):471-473.
[20]刘燕,买尔旦·马合木提,尼加提·热合木.新疆紫草提取物对小鼠急性四氯化碳性肝损伤的保护作用[J].时珍国医国药,2006,17(9):1676-1678.
[21]买尔旦·马合木提,刘燕,尼加提·热合木.新疆紫草提取物对D-氨基半乳糖致小鼠急性肝损伤的保护作用[J].中国中药杂志,2006,31(19):1646-1649.
[22]许今博,买尔旦·马合木提,于亚鹭.新疆紫草提取物对果蝇寿命的影响[J].新疆医科大学学报,2007,30(3):228-233.
[23]卢贺起,丁家欣,魏雅川等.紫草多糖粗提物的药效作用研究[J].中国药理学会通报,2000,17(4):26-27.
[24]罗学娅,李明辉,吕莉等.紫草的药理作用与应用研究进展[J].大连大学学报,2004,25(2):80-92.
[25]张玉萌.紫草多糖的研究概况[J].中国新医药,2004,3(4):54-55.
[2]葛锋,王晓东,王玉春.药用紫草的研究进展[J].中草药,2003,34(9):附6-7.
[3]卢贺起,丁家欣,魏雅川.紫草的实验研究进展[J].中国中医药信息杂志,1998,5(1):20-23.
[4]罗学娅,李明辉,吕莉等.紫草的药理作用与应用研究进展[J].大连大学学报,2004,25(2):80-92.
[5]黎玉红,周晓荣.新疆紫草的研究进展[J].新疆中医药,2002,20(4):75-77.
[6]黄志纾,张敏,马林等.紫草的化学成分及其药理活性研究概况[J].天然产物研究与开发,1999,12(l):73-82.
[7] Fumihiko Yoshizaki,Shuji Hisamichi,Yashikazu Kondo,et al.Studies on shikon.New furylhydroquinone derivatives,shikonofurans A,B,C,D and E from Lithospermum erythrorhizon Sieb.et Zucc.[J].Chemieal & Pharmaceutical Bull- erin ,1982,30(12):4407-4411.
[8]邵鹏飞.新疆紫草化学成分的研究[D].中国药科大学硕士学位论文,2001.
[9] I.Morimoto,T.Kishi,S.Ikegami. Naphthoquinone derivatives from Lithospermum erythrorhizon Sieb.et Zuec[J].Tetrahedron Letters,1965,(52):4737-4739.
[10] B.Bozan,K.H.C.Baser,S.Kara.Quantitative determination of naPhthaquinones of Arnebia densflora(Nordm.)Ledeb.by an improved high-performance liquid chromatographic method [J].Journal of Chromatography A,1997,782:133-136.
[11] YS.Chang,S.C.Kuo,S.H.Weng,et al.Inhibition of platelet aggregation by shikonin derivatives isolated from Arnebia euchroma[J].Journal of Medicinal Plant Research,1993,59(5):401-404.
[12]傅善林,肖培根.新疆软紫草中萘醌色素的研究[J].中草药,1986,17(10):2.
[13] Bai G .Chem Res Chinese Universities.1994,10(3):263.
[14] R.K.Khajuria,S.M.Jain. Two bew naphthoquinones from the roots of Onosoma hispidumt[J].Indian Journal of Chemistry,1993,32B:390-391.
[15] X.S.Yao,YE bizuka,H.Noguchi,et al.Sanikawa Biologieally active constituents of Arnebia euchroma:structure of arnebinol,an monoterpenylenzenoid with inhibitory activity on prostaglandin biosynthesis[J].Chemical and pharmaceutical Bulletin,1991,39(11):2956-2961.
[16]严松柏,谈献和,胡玉涛.紫草的研究进展[J].时珍国医国药,2003,14(2):103-105.
[17]吕秀芬,田景奎,周丽华.中药有效成分及其作用简述[J].时珍国药研究,1997,8(3):281.
[18]赵利.紫草的药理研究进展[J].武警医学,1997,8(2):115.
[19] [19]李忠良.紫草中紫草素的含量测定[J].药物分析杂志,1986,6(1):41.
[20] [20]张敏,金永清,郭兰建等.紫草的鉴别及其有效成分羟基萘醌色素类含量测定[J].中草药,1989,20(10):17-18.
[21]阎江丽,王建林.紫草中天然色素物化特性的研究[J].精细化工,1994,11(6):57.
[22]杨晓笛,卢锋,黄美充等.中药紫草有效成分的提取[J].汕头大学学报(自然科学版),2002,17(4):67-70.
[23]李惠兰,秦剑,何洪静等.滇紫草、新疆紫草和露蕊滇紫草提取物药效学研究[J].中国民族民间医药杂志,2002,12(3):174-176.
[24] Fukui H,Hasan A F M F,Kyo M.Formation and secretion of a unique quinone by hairy root cultures of Lithospermum erythrorhizon[J].Phytochemistry,1999,51(4): 511-515.
[25] Yamamoto H,Inouea K,Yazakib K.Caffeic acid oligomers in Lithospermum erythrorhizon cell suspension cultures[J].Phytochemistry,2000,53(6):651-657.
[26]孙培杰.紫草的药理作用与临床应用研究进展[J].中医药信息,2002,l9(4):19.
[27]沈映君.中药药理学[M].北京:人民卫生出版社,2O00,289-292.
[28] Li HY,Luo SR ,Zhou TH.Metabolism of Shikonin in Rats[J].Journal of Chinese Pharmaceutical Sciences,1999,8(3):148-151.
[29]辛玲.硬紫草质量评价研究[D].黑龙江中医药大学硕士学位论文,2008.
[30]张秀娟,刘佰华,穆坤等.紫草及其提取物生物学活性研究进展[J].中国微生态学杂志,2007,19(6):579.
[31]魏林,陈祥明,秦光.紫草油治疗放射性皮肤溃疡愈合观察[J].中国临床康复,2004,8(5):30.
[32]田世禹,于甬华,陈延条等.紫草等中药油膏治疗急性放射性皮肤损伤的疗效观察[J].肿瘤防治杂志,2002,9(4):25.
[33] Kiyoshi K,Malgoriats S,Howard L.percutaneous absorption:a single-layer model[J]. J Phrem Sci,1993,82(5):450.
[34] Korting HC.Eur J Clin Pharmaeol,1990,39:349.
[35] Schhreier H,Bouwstra J.Liposomes and niosomes as topical drug carrier:dermal and transdermal drug delivery[J]. J Controlled Release,1994,30:l-13.
[36]李国锋,侯连兵,曾抗.维甲酸脂质体的制备与临床应用[J].中国药学杂志,1998,33(2):121-122.
[37]何文,吴宏霞,蔡鸿生等.8-甲氧补骨脂素脂质体凝胶的研制[J].中国医院药学杂志,2004,24(1):3.
[38] Chung-SJ.Future drug delivery researeh in South Korea[J]. J-Controlled-Release,1999,62(l2):73-9.
[39] Michelson AM,Stadtman E,Boon P,et al.Decreased skin superoxide dismutase activity by a single exposure of ultraviolet radiation was reduced by liposomal superoxide petreatment[J].J Dermatol,1996,96(13):1376-1383.
[40] Plessis JD,Weiner N,Muller PG.The influence of in vivo treatment of skin with liposomes on the topical absorption of a hydrophilic and a hydrophobic drug in vitro[J].Int J Phann,1994,103(1):1-5.
[41] Lasch J,Wohlrab W.Liposome-bound cortisol:a new approach to cutaneous therapy[J].Biomed Biochim Acta,1996:45:1295-1299.
[42]张越珍,林军.天然药物脂质体制备研究进展[J].中国药房,2007,18(21):1671.
[43]张灵芝.脂质体制备及其在生物医学中的应用[M].北京医科大学、中国协和医科大学联合出版社,1998,101.
[44] Sharata HH. Int J Dermatol,1996,35(11):761.
[45] Roding J,Ghyczy M,Control of skin humidity with liposomes and stabilization of skin care oils and lipophilic active substances with liposomes [J].SOFW,1991,10:372.
[46] Mezei M,Gulasekharam V.Liposomes—a selective drug delivery system for the topical route of administration: I.Lotion dosage form[J].Life Sci,1980, 26:473-489.
[47]张路,简江波,盛燕等.马钱子碱脂质体的大鼠离体透皮性能和兔皮肤刺激性研究[J].中国医药工业杂志,2006,37(3):172.
[48]王欢,陆彬,杨红.咪喹莫特脂质体与乳膏体外经皮扩散行为的比较[J].中国医药工业杂志,2003,34(2):73-75.
[49]白铭,张恒术,王昆等.辣椒素脂质体在体外瘢痕组织中透皮吸收的研究[J].沈阳药科大学学报,2004,21(1):8-10.
[50] Row TC, Okamoto H, Weiner ND, et al. Mechanisms of topical delivery of liposomally entrapped drugs[J].Skin Pharmacol,1994,7:346-352.
[51] Gehring W, Klein M, Gloor M. Liposome Dermaties,1992,315.
[52] Sciliano AA, Martin GP, Montenegro L, et al. Procedure for preparation of liposomes with large interal aqueous space and high capture by reverse-phase evaporation[J].Adv Drug Delivery Rev,1996,18(3):303-308.
[53]吴宏霞,何文,蔡鸿生.脂质体作为皮肤局部给药载体的研究进展[J].中国现代应用药学杂志,2004,21(2):115.
[54]范芳芳,刘泽蒲,陈文等.紫外分光光度法测定新疆紫草中总萘醌的含量[J].石河子大学学报(自然科学版) ,2004,22 (5):425-426.
[55]杨秀芳.紫草提取工艺的优化[J].陕西科技大学学报,2004,22(4):5-37.
[56]马瑛,王嗣岑,黄猛.HPLC测定紫草中紫草素含量[J].中国药学杂志,2000,35 (2):98.
[57]谢秀琼,邱明丰.对制剂中紫草成分和提取工艺的探讨[J].中国药房,1997,8(2):60-61.
[58]李立荣,崔志高,肖润禾等.对紫草中紫草色素的初步研究[J].湖南中医学院学报,2000,20(2):25-27.
[59]赵雪梅,王桂玲,费洪荣等.紫草有效成分的提取及其抗炎作用研究[J].中药药理与临床2008,24(4):36-38.
[60]杨秀芳.正交实验法优选紫草的提取工艺[J].中成药,2005,27(3):351-353.
[61]吴学渊,刘萍.正交试验设计优选紫草的醇提工艺[J].中国医院用药评价与分析,2008,8(10):750-752.
[62]熊利容.白藜芦醇苷脂质体的制备及其药代动力学的研究[D].湖北中医学院硕士学位论文,2007.
[63]黄亚东,项琪,张宏波等.碱性成纤维细胞生长因子脂质体的制备和评价[J].中国药学杂志,2008,43(13):992-997.
[64]沃兴德,洪行球,高承贤等.姜黄素长期毒性试验[J].浙江中医学院学报,2000,24(1):61-65.
[65]张学农,孙殿甲,李观海.去氢骆驼蓬碱脂质体的研究[J].中国医药工业杂志,1994,25(10):441-445.
[66]吴明星,利华明,李绍珍等.骆驼蓬总碱及其脂质体对兔晶状体上皮细胞的抑制作用[J].眼科研究,1999,27(4):275.
[67]刘衍兴,郭辉.小糪碱及其脂质体降血搪作用实验研究[J].基层中药杂志,1999,13(1):18-19.
[68]薛玉英,翁帼英,何俊峰等.口服硫酸氢黄连素脂质体的研制[J].中国中药杂志,1995,20(12):730.
[69]穆筱梅,梁世强.脂质体的制备方法及其研究进展[J].时珍国医国药,2008,19(7):1784-1786.
[70]许汉林,孙芸,邵继征等.姜黄素脂质体的制备及理化性质考察[J].中国医院药学杂志,2007,27(10):1363-1365.
[71]李淑斌,刘丹,宁红等.紫杉醇固体脂质纳米粒包封率的测定[J].中国药学杂志,2008,43(21):1665-1668.
[72]国家药典委员会编.中华人民共和国药典(2005版,二部)[M].北京:化学工业出版社,2005,附录181.
[73]黄红兵,刘韬,徐月红等.多西紫杉醇脂质体制备工艺及处方优化研究[J].中国药学杂志,2007,42(24):1872-1876.
[74]张鹤鸣,穆成林.酮洛芬脂质体的制备和质量评价[J].中国医院药学杂志, 2007,27(8):1161-1163.
[75]徐晖,李英剑,严志等.黄体酮缓释凝胶的体外释放性质[J].中国药剂学杂志,2003,l(l):6-9.
[76]宋金春,陈佳丽,刘薇芝.葛根素前体脂质体的质量考察[J].中国医院药学杂志,2007,27(9):1244-1246.
[77]彭海龙,雷志强,刘燕燕等,槐定碱脂质体的制备及理化性质研究[J].中国医院药学杂志,2009,29(1):32-35.
[78]吕长江.愈肤灵乳膏制备及质量控制[J].浙江中西医结合杂志,2006,16(2):126.
[79]邢建国,孙殿甲,管慧等.盐酸去氢骆驼蓬碱软膏的处方筛选[J].中成药,2001,23(5):316-318.
[80]刘可春,刘昌衡,王希敏等.辣椒碱软膏基质及其配方的优选试验研究[J].2004,17(2):33-36.
[81]张学农,孙殿甲,周颖.利湿平软膏的处方筛选[J].中成药,1998,20(1):8-10.
[82]马萍,辛艳茹,杨京燕等.离心分光光度法测定乳剂稳定性[J].药学实践杂志,2001,19(l):23.
[83]向俊霖,张莉,王晓辉等.尼莫地平脂质体的制备及体外透皮研究[J].中国药房,2009,20(1):36-38.
[84]杨晓春,张强,吴镭.目前我国透皮给药系统研究的基本思路[J].中国新药杂志,2001,10(5):321-324.
[85]李琦,王凤山,凌沛学等.以玻璃酸钠为媒介对布洛芬体外释放及透皮吸收的影响[J].中国医院药学杂志,2007,27(9):1235-1238.
[86]朱亚丽,盛国荣.复方咪康吟乳膏动物实验研究[J].海峡药学,2005,17(6):59-60.
[87]刘丽春,腾宝霞,苏晓洁等.复方维甲酸霜的皮肤急性毒性、皮肤变态反应及刺激性实验研究[J].兰州大学学报(医学版),2005,31(3):61-62.
[88]徐淑云,卞如镰,陈修.药理实验方法学[M].北京人民卫生出版社, 2002,1537-1539.
[89]姜华.芦荟鼻按软膏药效学及毒理学实验研究[J].甘肃中医,2003,16(l):40-41.
[90]薛育梅.氯地霜动物实验研究[J].黑龙江医药,2004,17(6):420-421.
[91]李淑斌,刘丹,宁红等.紫杉醇固体脂质纳米粒包封率的测定[J].中国药学杂志,2008,43(21):1665-1668.
[1]葛锋,王晓东,王玉春.药用紫草的研究进展[J].中草药,2003,34(9):附6-10.
[2]初雨,潘晓玲.新疆药用资源植物及其开发利用现状[J].中国野生植物资源,20(1):21-23.
[3]史建玲,李琦,张春雨.新疆博尔塔拉蒙古自治州主产药材简介[J].新疆中医药,2002,20(4):43-44.
[4] [4]冯缨,严成,尹林克.新疆植物特有种及其分布[J].西北物学报,2003,23(2):263-273.
[5]黄志纾,张敏,马林等.紫草的化学成分及其药理活性研究概况[J].天然产物研究与开发,2000,12(1):72-82.
[6]蒋英丽,宋今丹.新疆紫草素诱导人大肠癌细胞的凋亡[J].癌症,2001,20 (12):1355-1358.
[7] Singh F,Gao D,Lebwohl MG,et a1.Shikonin modulates cell proliferation by inhibiting epidermal growth factor receptor signaling in human epidermoid carcinoma cells[J].Cancer Lettr,2003,200(2):115-121.
[8] Wu Z,Wu L,Li L,et a1.p53-Mediated cell cycle arrest and apoptosis induced by shikonin via a caspase-9-dependent mechanism in human malignant melanoma A375-S2 cells[J].J Pharmacol Sci,2004,94(2):166-176.
[9]张阳,王英丽,齐红等.新疆紫草素抗肝癌的实验研究[J].实用肿瘤学杂志,2006,20(4):294-295.
[10]徐贵颖,郭敏,王英丽.新疆紫草素对荷H22肝癌小鼠抗肿瘤的实验性研究[J].中华医学全科杂志,2004,5(3):22-24.
[11]林江,韩福刚,王开正等.新疆紫草素对肿瘤细胞生长抑制作用的研究[J].泸州医学院学报,2003,26(2):102-105.
[12] Gaddipati J P, Mani H,Shefali,et a1.Inhibition of growth and regulation of IGFs and VEGF in human prostate cancer cell lines by shikonin analogue 93/637(SA)[J].Anticancer Res,2000,20(4):2547-2552.
[13] Hashimoto S,Xu M,M asuda Y,et a1.beta-hydroxyisovalerylshikonin inhibits the cell growth of various cancer cell lines and induces apoptosis in leukemia HL-60 cells through a mechanism different from those of Fas and etoposide[J].J Biochem(Tokyo),1999,125(1):17-23.
[14]胡艳萍,王骏业.紫草素增加小鼠肝癌和Lewis肺癌放射治疗效应的初步研究[J].肿瘤防治研究,1991,18(2):71-73.
[15]王薇,李萍萍.紫草提取物对MCF-7细胞及小鼠雌孕激素水平的影响[J].中国中药杂志,2003,28(11):1062-1067.
[16]刘梅青.不同剂量紫草醇提取物对表皮细胞过度增殖的实验研究[J].临床医药实践杂志,2003,12(7):485-487.
[17]吴晓霞,周武庆.紫草素对角质形成细胞株增殖的抑制及凋亡的作用[J].中国麻风皮肤病杂志,2003,19(6):563-566.
[18]买尔旦·马合木提,刘燕,古丽仙·胡加等.新疆紫草提取物对小鼠急性酒精性肝损伤的保护作用[J].中国药物与临床,2007,7(4):284-286.
[19]刘燕,买尔旦·马合木提,尼加提·热合木.新疆紫草提取物对小鼠免疫性肝损伤的保护作用[J].新疆医科大学学报,2006,29(6):471-473.
[20]刘燕,买尔旦·马合木提,尼加提·热合木.新疆紫草提取物对小鼠急性四氯化碳性肝损伤的保护作用[J].时珍国医国药,2006,17(9):1676-1678.
[21]买尔旦·马合木提,刘燕,尼加提·热合木.新疆紫草提取物对D-氨基半乳糖致小鼠急性肝损伤的保护作用[J].中国中药杂志,2006,31(19):1646-1649.
[22]许今博,买尔旦·马合木提,于亚鹭.新疆紫草提取物对果蝇寿命的影响[J].新疆医科大学学报,2007,30(3):228-233.
[23]卢贺起,丁家欣,魏雅川等.紫草多糖粗提物的药效作用研究[J].中国药理学会通报,2000,17(4):26-27.
[24]罗学娅,李明辉,吕莉等.紫草的药理作用与应用研究进展[J].大连大学学报,2004,25(2):80-92.
[25]张玉萌.紫草多糖的研究概况[J].中国新医药,2004,3(4):54-55.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |