复方白花蛇舌草片剂的制备及质量评价
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摘要
肺癌的发病率、死亡率近年呈逐步上升的趋势。在我国,肺癌的发病人数已居恶性肿瘤首位。以铂类药物为基础的联合化疗,虽可延长患者生存期,但存在副作用大、敏感性降低等问题。临床研究表明,中药治疗与化疗配合,可以减轻化疗不良反应、提高疗效。肺癌属内热阴虚证,而白花蛇舌草(蛇舌草)、白英合用有清热解毒、补益消壅之效。本文从中医理论的角度阐述了蛇舌草、白英配伍协同作用治疗肺癌的机理,旨在研究开发一种可用于肺癌治疗的中药复方制剂。复方中主要抗癌有效部位为蛇舌草中多糖、白英中甾体皂苷成分。本试验对药材中有效部位提取工艺、片剂制备工艺、制剂质量与稳定性进行了比较系统的研究。
建立以多糖、甾体皂苷为指标成分的含量检测方法。采用可见分光光度法分别在486nm、410nm、486nm处测定提取物中多糖、甾体皂苷及制剂中多糖含量;采用高效液相色谱法,以纯甲醇为流动相,在205nm处测定制剂中甾体皂苷含量,用于制剂的质量控制。方法学考察结果证明含量测定方法均准确、灵敏、稳定性良好。
在单因素试验基础上,采用正交设计优化蛇舌草多糖的水提、醇沉工艺条件,以出膏率、浸膏中多糖含量为指标,确定水回流提取工艺为10倍药材量的溶剂,提取3次,每次1小时;醇沉工艺为药液浓缩率0.25g/ml,醇沉浓度60%。药材出膏率为11.62%,浸膏中多糖含量为10.07%。
分别采用乙醇超声法、乙醇回流法对白英中甾体皂苷成分进行提取,结果表明乙醇回流法提取效果较好。对乙醇回流提取工艺进行优化,确定工艺条件为10倍药材量的50%乙醇,提取3次,每次2小时。药材出膏率为12.35%,浸膏中甾体皂苷含量为1.29%。通过静态吸附、解吸试验比较不同型号大孔吸附树脂对白英提取液中甾体皂苷的吸附、解吸性能,确定使用LSA-10型树脂。采用单因素比较法优化甾体皂苷的吸附、洗脱条件,确定纯化工艺为药液浓缩比0.4(g生药):1(ml药液),上样流速2.0ml/min,树脂柱径高比1:10,树脂处理量为每g干树脂处理0.8g生药,醇洗浓度50%,洗脱流速3.0ml/min,洗脱剂用量100ml。浸膏中甾体皂苷含量可达到12.48%。
蛇舌草、白英两味药材在其他抗癌复方中配伍使用时常等量应用,本方使用相同配比。依据药材的出膏率对浸膏量与原药材量进行换算,浸膏粉的混合比例为9:1。以制剂的外观、硬度、脆碎度、崩解时限为评价指标,对填充剂、润湿剂、崩解剂、润滑剂进行预选,并以正交设计对预选辅料进行优化组合,确定制剂成型工艺为取过80目筛药材浸膏粉10.0g,加入6.0g糊精、4.0g微晶纤维素以及0.3g羧甲淀粉钠,混合均匀,以适量95%乙醇润湿,制软材,过16目筛制粒,55℃干燥3小时,过筛整粒,加入羧甲基淀粉钠0.3g、硬脂酸镁0.05g,混合均匀,压制得100片。
本试验从性状、崩解时限、片重差异、含量测定等方面对制剂质量进行综合评价,并对制剂的稳定性进行初步考察,结果表明所制片剂质量可控,具有轻微吸湿性,宜采取包衣措施,增强其防潮性能。
Lung cancer is a frequently occurring,mostly lethal disease in all countries worldwide in recent years. It is one of the most commonly diagnosed types of cancer and has the highest death rates in China. The combined chemotherapy based on platinium regimens modestly prolong survival in lung cancer.Whereas,side effects and chemotherapy resistance factors remain in the treatment for lung cancer patients. Clinical data demonstrated that a gain can be expected in reduction of side effects and enhancement of therapeutic effects after combined chemotherapy with traditional Chinese medicine. From a theoretical point of traditional Chinese medicine,the present study explained the mechanism to inhibit tumor growth in the face of the treatment in which combined Hedyotis diffusa Willd. with Solanum lyratum Thunb.. The aim of this study was to provide an effective medicament that can prevent and cure lung cancer. Polysaccrides in Hedyotis diffusa and steroidal saponins in Solanum lyratum were the active components in the compound recipe. This study maily dealt with the extraction process of active components, preparation procedure,quality control and stability of the preparation.
To establish the method of determining indicatrix components for quality control. The determination of polysaccrides (in preparation),steroidal saponins in extractum was achieved at 486nm,410nm by visible spectrophotometry. The determination of steroidal saponins in preparation was achieved at 205nm by high performance liquid chromatography (HPLC) with mobile phase containing pure methanol. These methods were established to determinate polysaccrides and steroidal saponins with high resolution and efficiency.
Taking the yields of extractum and the content of polysaccrides as index,the optimal process of extracting polysaccrides with hot water as the extractant was investigated by orthogonal design. The defined process was as follows. The split materials of Hedyotis diffusa were extracted successively with hot water whose volume was 10 times of the weight of the herb for 1 hour,and the process of extraction was repeated 3 times. After the extractant was concentrated to 0.25g/ml,the crude polysaccrides were precipitated from the 60% ethanol solution. The yield of extractum from the herb was 11.62%,the contents of polysaccrides were 10.07%.
Comparing the extraction efficency of ethanol ultrasonic method and ethanol refluxing method to steroidal saponins in Solanum lyratum. As a result,ethanol refluxing method had higher performance. After optimizing the extraction process,conditions were identified as follows. The split materials of the herb were extracted successively with 50% ethanol whose volume was 10 times of the weight of the herb for 2 hour,and the prosess was repeated for 3 times. The yield of extactum was 12.53%,and the contents of steroidal saponins were 1.29%.
To study the characteristics of different types of macroporus resins through static adsorption and desorption tests to steroidal saponins in Solanum lyratum extractant,resin LSA-10 was decided to use. Single factor comparative method was used to idetify the adsorption and desorption conditions of steroidal saponins in resin. The defined process was that extractant condensation ratio was 0.4g/ml,flow rate was 2.0ml/min,ratio of diametre to height was 1:10,eluent solution was 50% ethanol,eluting rate was 3.0ml/min,volume of eluent was 100ml,0.8g split materials could be dealt by 1g dry resin. The contents of steroidal saponins in extractum were 12.48%.
The two herbs were mostly used with equal quantity in other compound recipes,the present study adhered to the same ratio. As speculated to the weight of crude herbs,the mixing ratio extractum was 9:1 (Hedyotis diffusas vs Solanum lyratum). Taking the appearance,hardness, fragibility,disintigration time of the preparation as index,the study preselected excipients such as fillers,moistening agents,disintegrants,lubricants in the formation process of preparation. Optimized the assembly of excipients by orthogonal design,the formula was identified as follows,extractum mixture of drug (which was filtered by sieve with 80 meshes) 10.0g,dextrin 6.0g,microcrystalline cellulose (MCC) 4.0g,magnism stearate 0.05g,carboxymethyline starch sodium (CMS-Na) 0.6g. The procedure of tablet preparing was that mixing extractum mixture with other excipients to be well-distributed,moistened with 95% ethanol solution,filtered by sieve with 16 meshes,dried at 55℃,sorted the particles by sieve with 16 meshes again,took CMS-Na 0.3g,magnesium stearate 0.05g in the sorted particles,stirred to be well-distributed. The particles were fed through a tablet machine,practically all the materials were pressed into 100 tablets.
The present study evaluated the quality of the preparation from aspects of characteristics, disintegration time,weight variance,content determination of effective components synthetically, and investigated the stability of the preparation primarily. The results showed that the preparation procedure of tablets was reasonable in technics,controllable in quality. According to the preparation stability,it indicated that the preparation showed slight hydroscopicity which should be coated modestly to boost the dampproof capacity.
建立以多糖、甾体皂苷为指标成分的含量检测方法。采用可见分光光度法分别在486nm、410nm、486nm处测定提取物中多糖、甾体皂苷及制剂中多糖含量;采用高效液相色谱法,以纯甲醇为流动相,在205nm处测定制剂中甾体皂苷含量,用于制剂的质量控制。方法学考察结果证明含量测定方法均准确、灵敏、稳定性良好。
在单因素试验基础上,采用正交设计优化蛇舌草多糖的水提、醇沉工艺条件,以出膏率、浸膏中多糖含量为指标,确定水回流提取工艺为10倍药材量的溶剂,提取3次,每次1小时;醇沉工艺为药液浓缩率0.25g/ml,醇沉浓度60%。药材出膏率为11.62%,浸膏中多糖含量为10.07%。
分别采用乙醇超声法、乙醇回流法对白英中甾体皂苷成分进行提取,结果表明乙醇回流法提取效果较好。对乙醇回流提取工艺进行优化,确定工艺条件为10倍药材量的50%乙醇,提取3次,每次2小时。药材出膏率为12.35%,浸膏中甾体皂苷含量为1.29%。通过静态吸附、解吸试验比较不同型号大孔吸附树脂对白英提取液中甾体皂苷的吸附、解吸性能,确定使用LSA-10型树脂。采用单因素比较法优化甾体皂苷的吸附、洗脱条件,确定纯化工艺为药液浓缩比0.4(g生药):1(ml药液),上样流速2.0ml/min,树脂柱径高比1:10,树脂处理量为每g干树脂处理0.8g生药,醇洗浓度50%,洗脱流速3.0ml/min,洗脱剂用量100ml。浸膏中甾体皂苷含量可达到12.48%。
蛇舌草、白英两味药材在其他抗癌复方中配伍使用时常等量应用,本方使用相同配比。依据药材的出膏率对浸膏量与原药材量进行换算,浸膏粉的混合比例为9:1。以制剂的外观、硬度、脆碎度、崩解时限为评价指标,对填充剂、润湿剂、崩解剂、润滑剂进行预选,并以正交设计对预选辅料进行优化组合,确定制剂成型工艺为取过80目筛药材浸膏粉10.0g,加入6.0g糊精、4.0g微晶纤维素以及0.3g羧甲淀粉钠,混合均匀,以适量95%乙醇润湿,制软材,过16目筛制粒,55℃干燥3小时,过筛整粒,加入羧甲基淀粉钠0.3g、硬脂酸镁0.05g,混合均匀,压制得100片。
本试验从性状、崩解时限、片重差异、含量测定等方面对制剂质量进行综合评价,并对制剂的稳定性进行初步考察,结果表明所制片剂质量可控,具有轻微吸湿性,宜采取包衣措施,增强其防潮性能。
Lung cancer is a frequently occurring,mostly lethal disease in all countries worldwide in recent years. It is one of the most commonly diagnosed types of cancer and has the highest death rates in China. The combined chemotherapy based on platinium regimens modestly prolong survival in lung cancer.Whereas,side effects and chemotherapy resistance factors remain in the treatment for lung cancer patients. Clinical data demonstrated that a gain can be expected in reduction of side effects and enhancement of therapeutic effects after combined chemotherapy with traditional Chinese medicine. From a theoretical point of traditional Chinese medicine,the present study explained the mechanism to inhibit tumor growth in the face of the treatment in which combined Hedyotis diffusa Willd. with Solanum lyratum Thunb.. The aim of this study was to provide an effective medicament that can prevent and cure lung cancer. Polysaccrides in Hedyotis diffusa and steroidal saponins in Solanum lyratum were the active components in the compound recipe. This study maily dealt with the extraction process of active components, preparation procedure,quality control and stability of the preparation.
To establish the method of determining indicatrix components for quality control. The determination of polysaccrides (in preparation),steroidal saponins in extractum was achieved at 486nm,410nm by visible spectrophotometry. The determination of steroidal saponins in preparation was achieved at 205nm by high performance liquid chromatography (HPLC) with mobile phase containing pure methanol. These methods were established to determinate polysaccrides and steroidal saponins with high resolution and efficiency.
Taking the yields of extractum and the content of polysaccrides as index,the optimal process of extracting polysaccrides with hot water as the extractant was investigated by orthogonal design. The defined process was as follows. The split materials of Hedyotis diffusa were extracted successively with hot water whose volume was 10 times of the weight of the herb for 1 hour,and the process of extraction was repeated 3 times. After the extractant was concentrated to 0.25g/ml,the crude polysaccrides were precipitated from the 60% ethanol solution. The yield of extractum from the herb was 11.62%,the contents of polysaccrides were 10.07%.
Comparing the extraction efficency of ethanol ultrasonic method and ethanol refluxing method to steroidal saponins in Solanum lyratum. As a result,ethanol refluxing method had higher performance. After optimizing the extraction process,conditions were identified as follows. The split materials of the herb were extracted successively with 50% ethanol whose volume was 10 times of the weight of the herb for 2 hour,and the prosess was repeated for 3 times. The yield of extactum was 12.53%,and the contents of steroidal saponins were 1.29%.
To study the characteristics of different types of macroporus resins through static adsorption and desorption tests to steroidal saponins in Solanum lyratum extractant,resin LSA-10 was decided to use. Single factor comparative method was used to idetify the adsorption and desorption conditions of steroidal saponins in resin. The defined process was that extractant condensation ratio was 0.4g/ml,flow rate was 2.0ml/min,ratio of diametre to height was 1:10,eluent solution was 50% ethanol,eluting rate was 3.0ml/min,volume of eluent was 100ml,0.8g split materials could be dealt by 1g dry resin. The contents of steroidal saponins in extractum were 12.48%.
The two herbs were mostly used with equal quantity in other compound recipes,the present study adhered to the same ratio. As speculated to the weight of crude herbs,the mixing ratio extractum was 9:1 (Hedyotis diffusas vs Solanum lyratum). Taking the appearance,hardness, fragibility,disintigration time of the preparation as index,the study preselected excipients such as fillers,moistening agents,disintegrants,lubricants in the formation process of preparation. Optimized the assembly of excipients by orthogonal design,the formula was identified as follows,extractum mixture of drug (which was filtered by sieve with 80 meshes) 10.0g,dextrin 6.0g,microcrystalline cellulose (MCC) 4.0g,magnism stearate 0.05g,carboxymethyline starch sodium (CMS-Na) 0.6g. The procedure of tablet preparing was that mixing extractum mixture with other excipients to be well-distributed,moistened with 95% ethanol solution,filtered by sieve with 16 meshes,dried at 55℃,sorted the particles by sieve with 16 meshes again,took CMS-Na 0.3g,magnesium stearate 0.05g in the sorted particles,stirred to be well-distributed. The particles were fed through a tablet machine,practically all the materials were pressed into 100 tablets.
The present study evaluated the quality of the preparation from aspects of characteristics, disintegration time,weight variance,content determination of effective components synthetically, and investigated the stability of the preparation primarily. The results showed that the preparation procedure of tablets was reasonable in technics,controllable in quality. According to the preparation stability,it indicated that the preparation showed slight hydroscopicity which should be coated modestly to boost the dampproof capacity.
引文
[1]王宏宇.晚期肺癌二线治疗最新进展.医学研究杂志,2006,35(2):58~60.
[2]周宜强,史国军.中西医结合治疗中晚期肺癌现状及前景.中医药管理杂志,2007,15(1):63~65.
[3]刘艳清.中药抗癌机制的实验研究进展.光明中医,2007,22(4):67~70.
[4]赵黎.肺癌的中医治疗.现代中西医结合杂志,2007,16(31):4605~4606.
[5]周宜强主编.实用中医肿瘤学.北京:中医古籍出版社,2006,367.
[6]金萍.肺癌的中医证治探讨.浙江中医杂志,2006,41(6):343.
[7]姚艳红,董方言.白花蛇舌草抗肿瘤研究进展.中国药房,2006,17(6):1261~1262.
[8]吴婉莹,高志刚,李云谷,等.白英和欧白英的化学成分与药理活性.国外医药·植物药分册,2001,16(6):245~247.
[9]陈贵庭主编.本草纲目通释,上卷.北京:学苑出版社,1992,1120.
[10]江苏省卫生厅.江苏省中药材标准.南京:江苏科学技术出版社,1989,81~83.
[11]单保恩,张金艳,杜肖娜,等.白花蛇舌草的免疫学调节活性和抗肿瘤活性.中国中西医结合杂志,2001,21(5):370~374.
[12]谢宗万主编.汉拉英对照中药材正名词典.北京:科学技术出版社,2004,801.
[13] Kang SY,Sung SH,Park JH,et al.Hepatoprotective activity of scopoletin, a constituent of Solanum lyratum.Archives of Pharmacal Research,1998,21(6):718~722.
[14] Kim HM,Kim MJ,Li E,et al.The nitric oxide-producing properties of Solanum lyratum.Journal of Ethnopharmacology,1999,67(2):163~169.
[15]尹礼烘.白英诱导人肺癌SPC-A-1细胞凋亡实验研究:[硕士学位论文].南昌:江西医学院,2002.
[16]陈周全,徐莲英.大孔吸附树脂在中药有效成分分析中的应用.中国药品标准,2000,1(1):21~22.
[17]李平华,王兴文.大孔吸附树脂在中药有效成分分离纯化中的研究进展.云南中医学院学报,2003,26(3):43~48.
[18]谢秀琼主编.现代中药制剂新技术.北京:化学工业出版社,2004,70.
[19]刘小平主编.中药分离工程.北京:化学工业出版社,2004,97.
[20]陆彬主编.药剂学.北京:中国医药科技出版社,2003,164.
[21] Li R,Zhao HR,Li YN.Antitumor effect and protective effect on chemotherapeutic damage of water soluble extracts from Hedyotis diffusa.Journal of Chinese Pharmaceutical Sciences,2002,11(2):54~58.
[22]任靖,冯国楠,王敏伟,等.白英总苷抗肿瘤作用初步研究.肿瘤防治研究,2006,33(4):262~264.
[23]刘志刚.白花蛇舌草化学成分研究及抑瘤活性成分筛选:[硕士学位论文].广州:第一军医大学,2002.
[24]王晖,刘良玉,陈梅荣,等.灵芝软胶囊中多糖含量的测定.江西中医学院学报,2002,14(4):34.
[25]王新,陆慧宁,林少琨.苦丁茶冬青叶多糖的提取及含量测定.时珍国医国药,2006,17(10):1977~1979.
[26]都述虎,夏重道,付铁军,等.穿龙薯蓣总皂甙水解条件的优化.中成药,2000,22(9):608~610.
[27]鲁鑫焱,赵怀清.薯蓣皂苷元的提取与分离分析方法.沈阳药科大学学报,2003,20(6):465~468.
[28] Sadava D,Ahn J,Zhan M,et al.Effects of four Chinese herbal extracts on drug-sensitive and multidrug-resistant small-cell lung carcinoma cells.Cancer Chemother Pharmacol,2002,49(4):261.
[29] Adiaratou T,Marit I,Drissa D,et al.Polysaccharides with complement fixing and macrophage stimulation activity from Opilia celtidifolia , isolation and partial characterisation.Journal of Ethnopharmacology,2008,1154:423~431.
[30] Yu RM ,Wang L,Zhang H,et al.Isolation,purification and identification of polysaccharides from cultured Cordyceps militaris.Fitoterapia,2004,75:662~ 666.
[31] Meng-Hsin Lee,Jing-Jy Cheng,Cha-Yui Lin,et al.Precursor-feeding strategy for the production of solanine , solanidine and solasodine by a cell culture of Solanum lyratum. Process Biochemistry,2007,42:899~903.
[32]杨健,苗芳,赵伟,等.正交设计优选帖筷子甾体皂苷成分的超声提取工艺.西北农业学报,2007,16(2):90~93.
[33]王俊,陈钧,杨克迪,等.水解原位萃取薯蓣皂苷元的工艺条件研究.中国中药杂志,2003,28(10):934~937.
[34]刘斌,石任兵,余超,等.应用大孔吸附树脂吸附分离技术制备蒲黄总黄酮的研究.北京中医药大学学报,2002,25(4):25~28.
[35]侯世祥,田恒康.大孔吸附树脂在中药复方分离纯化工艺中的应用.中药新药与临床药理,2000,11(3):131~133.
[36]白林,杨帆,王晓蕾.消渴化瘀片质控方法的研究,解放军药学学报,2006,22(5):379-382.
[37]马丽萍.降糖益肾制剂的药学研究:[硕士学位论文].上海:上海交通大学,2007.
[38]侯惠民主编.药用辅料应用技术.北京:中国医药科技出版社,2002,73.
[39]赵景婵,郭治安,成小飞,等.穿龙薯蓣中薯蓣皂苷元的高效液相色谱法测定.药物分析杂志,2000,20(1):27~29.
[40]都述虎,王晓华,夏重道,等.RP-HPLC法测定穿龙薯蓣总皂甙中薯蓣皂甙元的含量.中国药科大学学报,2001,32(1):37~40.
[41]田丰,邓英杰.HPLC法测定黄芪中黄芪甲苷含量.沈阳药科大学学报,2000,17(1):43~45.
[42]周钢,葛斌,唐星.高效液相色谱法测定咳喘胶囊中薯蓣皂苷元的含量.中国中药杂志,2002,27(8):625~626.
[1]谢宗万主编.汉拉英对照中药材正名词典,上卷.北京:科学技术出版社,2004,801.
[2]《全国中草药汇编》编写组.全国中草药汇编,上册.北京:人民卫生出版社,1983,291.
[3]陈贵庭主编.本草纲目通释,上卷.北京:学苑出版社,1992,1120.
[4]吴婉莹,高志刚,李云谷,等.白英和欧白英的化学成分与药理活性.国外医药·植物药分册,2001,16(6):245~247.
[5]张宁.中草药白英中常见化学成分分析方法的研究:[硕士学位论文].郑州:郑州大学,2007.
[6] Murakami K,Saijo R,Nohara T,et al.Studies on the constituents of Solanum Plants.Ⅰ.On the constituents of the stem parts of Solanum lyratum Thunb.Yakugaku Zasshi,1981,101(3):275~279.
[7] Murakami K,Ezima H,Takaishi Y,et al.Studies on the constituents of Solanum Plants.Ⅴ.The constituents of Solanum lyratum ThunbⅡ.Chem Pharm Bull,1985,33(1):67~73.
[8] Yung-yung Lee.Studies on the Solanum lyratum.Chem Bull,1997,45(8):1381~1382.
[9]杨敬芝,郭贵明,周立新,等.白英化学成分的研究.中国中药杂志,2002,27(1):42~43.
[10]徐顺,王林江,李瑞玲,等.白英全草中挥发油化学成分分析.时珍国医国药,2006,17(8):1390~1391.
[11] Kang SY,Sung SH,Park JH,et al.Hepatoprotective activity of scopoletin, a constituent of Solanum lyratum.Archives of Pharmacal Research,1998,21(6):718~722.
[12] Yu SM,Kim HJ,Woo JH,et al.Some sesquiterpenoids and 5α,8α-epidioxy-sterols from Solanum lyratum.Archives of Pharmacal Research,1994,17(1):1.
[13]佐藤昭彦.新しぃ抗が生药の探究されゐ汉方用生药の作用.汉方研究,1979,2:11~22.
[14]曹济远,谭湘陵.抗癌中药白毛藤对CHO细胞G2-PC染色体畸变的观察.现代应用药学,1988,5(6):1~3.
[15]施文荣,刘艳.白英对人急性早幼粒细胞白血病HL-60细胞生长的影响.福建中医学院学报,2002,12(1):36-38.
[16]单长民,胡娟娟,杜冠华.白英提取物诱导人肝癌BEL-7404细胞凋亡作用.中国临床药理学与治疗学,2001,6(3):200~203.
[17]任靖,冯国楠,王敏伟,等.白英总苷抗肿瘤作用初步研究.肿瘤防治研究,2006,33(4):262~264.
[18]任靖,冯国楠,王敏伟,等.白英乙醇提取物抗肿瘤作用初步研究.中国中药杂志,2006,31(6):497~500.
[19]孙立新,任靖,王敏伟,等.白英水提物抗肿瘤作用的初步研究.中草药,2006,37(1):98~100.
[20]涂硕.白英提取液诱导人肺癌A549细胞凋亡及其机制研究:[硕士学位论文].南昌:南昌大学,2006.
[21] Kim HM,Lee EJ.Solanum lyratum inhibits anaphylactic reaction and suppression of L-histidine decarboxylase mRNA.Immunopharmacology and Immunotoxicology,1998,20(1):135~146.
[22]谢永芳,廖系晗,梁亦龙,等.白英提取物的抗氧化作用研究.时珍国医国药,2006,17(6):899~900.
[23] Kim HM,Kim MJ,Li E,et al.The nitric oxide-producing properties of Solanum lyratum.Journal of Ethnopharmacology,1999,67(2):163~169.
[24]谢永芳,梁亦龙,舒坤贤,等.白英提取物的免疫调节作用研究.时珍国医国药,2007,18(2):386~387.
[25]张民庆.抗肿瘤中药的临床应用.北京:人民卫生出版社,1998,160.
[26]石晓兰.养阴清热解毒法治疗恶性肿瘤阴虚内热证临床研究.江苏中医药,2004,25(7):17.
[2]周宜强,史国军.中西医结合治疗中晚期肺癌现状及前景.中医药管理杂志,2007,15(1):63~65.
[3]刘艳清.中药抗癌机制的实验研究进展.光明中医,2007,22(4):67~70.
[4]赵黎.肺癌的中医治疗.现代中西医结合杂志,2007,16(31):4605~4606.
[5]周宜强主编.实用中医肿瘤学.北京:中医古籍出版社,2006,367.
[6]金萍.肺癌的中医证治探讨.浙江中医杂志,2006,41(6):343.
[7]姚艳红,董方言.白花蛇舌草抗肿瘤研究进展.中国药房,2006,17(6):1261~1262.
[8]吴婉莹,高志刚,李云谷,等.白英和欧白英的化学成分与药理活性.国外医药·植物药分册,2001,16(6):245~247.
[9]陈贵庭主编.本草纲目通释,上卷.北京:学苑出版社,1992,1120.
[10]江苏省卫生厅.江苏省中药材标准.南京:江苏科学技术出版社,1989,81~83.
[11]单保恩,张金艳,杜肖娜,等.白花蛇舌草的免疫学调节活性和抗肿瘤活性.中国中西医结合杂志,2001,21(5):370~374.
[12]谢宗万主编.汉拉英对照中药材正名词典.北京:科学技术出版社,2004,801.
[13] Kang SY,Sung SH,Park JH,et al.Hepatoprotective activity of scopoletin, a constituent of Solanum lyratum.Archives of Pharmacal Research,1998,21(6):718~722.
[14] Kim HM,Kim MJ,Li E,et al.The nitric oxide-producing properties of Solanum lyratum.Journal of Ethnopharmacology,1999,67(2):163~169.
[15]尹礼烘.白英诱导人肺癌SPC-A-1细胞凋亡实验研究:[硕士学位论文].南昌:江西医学院,2002.
[16]陈周全,徐莲英.大孔吸附树脂在中药有效成分分析中的应用.中国药品标准,2000,1(1):21~22.
[17]李平华,王兴文.大孔吸附树脂在中药有效成分分离纯化中的研究进展.云南中医学院学报,2003,26(3):43~48.
[18]谢秀琼主编.现代中药制剂新技术.北京:化学工业出版社,2004,70.
[19]刘小平主编.中药分离工程.北京:化学工业出版社,2004,97.
[20]陆彬主编.药剂学.北京:中国医药科技出版社,2003,164.
[21] Li R,Zhao HR,Li YN.Antitumor effect and protective effect on chemotherapeutic damage of water soluble extracts from Hedyotis diffusa.Journal of Chinese Pharmaceutical Sciences,2002,11(2):54~58.
[22]任靖,冯国楠,王敏伟,等.白英总苷抗肿瘤作用初步研究.肿瘤防治研究,2006,33(4):262~264.
[23]刘志刚.白花蛇舌草化学成分研究及抑瘤活性成分筛选:[硕士学位论文].广州:第一军医大学,2002.
[24]王晖,刘良玉,陈梅荣,等.灵芝软胶囊中多糖含量的测定.江西中医学院学报,2002,14(4):34.
[25]王新,陆慧宁,林少琨.苦丁茶冬青叶多糖的提取及含量测定.时珍国医国药,2006,17(10):1977~1979.
[26]都述虎,夏重道,付铁军,等.穿龙薯蓣总皂甙水解条件的优化.中成药,2000,22(9):608~610.
[27]鲁鑫焱,赵怀清.薯蓣皂苷元的提取与分离分析方法.沈阳药科大学学报,2003,20(6):465~468.
[28] Sadava D,Ahn J,Zhan M,et al.Effects of four Chinese herbal extracts on drug-sensitive and multidrug-resistant small-cell lung carcinoma cells.Cancer Chemother Pharmacol,2002,49(4):261.
[29] Adiaratou T,Marit I,Drissa D,et al.Polysaccharides with complement fixing and macrophage stimulation activity from Opilia celtidifolia , isolation and partial characterisation.Journal of Ethnopharmacology,2008,1154:423~431.
[30] Yu RM ,Wang L,Zhang H,et al.Isolation,purification and identification of polysaccharides from cultured Cordyceps militaris.Fitoterapia,2004,75:662~ 666.
[31] Meng-Hsin Lee,Jing-Jy Cheng,Cha-Yui Lin,et al.Precursor-feeding strategy for the production of solanine , solanidine and solasodine by a cell culture of Solanum lyratum. Process Biochemistry,2007,42:899~903.
[32]杨健,苗芳,赵伟,等.正交设计优选帖筷子甾体皂苷成分的超声提取工艺.西北农业学报,2007,16(2):90~93.
[33]王俊,陈钧,杨克迪,等.水解原位萃取薯蓣皂苷元的工艺条件研究.中国中药杂志,2003,28(10):934~937.
[34]刘斌,石任兵,余超,等.应用大孔吸附树脂吸附分离技术制备蒲黄总黄酮的研究.北京中医药大学学报,2002,25(4):25~28.
[35]侯世祥,田恒康.大孔吸附树脂在中药复方分离纯化工艺中的应用.中药新药与临床药理,2000,11(3):131~133.
[36]白林,杨帆,王晓蕾.消渴化瘀片质控方法的研究,解放军药学学报,2006,22(5):379-382.
[37]马丽萍.降糖益肾制剂的药学研究:[硕士学位论文].上海:上海交通大学,2007.
[38]侯惠民主编.药用辅料应用技术.北京:中国医药科技出版社,2002,73.
[39]赵景婵,郭治安,成小飞,等.穿龙薯蓣中薯蓣皂苷元的高效液相色谱法测定.药物分析杂志,2000,20(1):27~29.
[40]都述虎,王晓华,夏重道,等.RP-HPLC法测定穿龙薯蓣总皂甙中薯蓣皂甙元的含量.中国药科大学学报,2001,32(1):37~40.
[41]田丰,邓英杰.HPLC法测定黄芪中黄芪甲苷含量.沈阳药科大学学报,2000,17(1):43~45.
[42]周钢,葛斌,唐星.高效液相色谱法测定咳喘胶囊中薯蓣皂苷元的含量.中国中药杂志,2002,27(8):625~626.
[1]谢宗万主编.汉拉英对照中药材正名词典,上卷.北京:科学技术出版社,2004,801.
[2]《全国中草药汇编》编写组.全国中草药汇编,上册.北京:人民卫生出版社,1983,291.
[3]陈贵庭主编.本草纲目通释,上卷.北京:学苑出版社,1992,1120.
[4]吴婉莹,高志刚,李云谷,等.白英和欧白英的化学成分与药理活性.国外医药·植物药分册,2001,16(6):245~247.
[5]张宁.中草药白英中常见化学成分分析方法的研究:[硕士学位论文].郑州:郑州大学,2007.
[6] Murakami K,Saijo R,Nohara T,et al.Studies on the constituents of Solanum Plants.Ⅰ.On the constituents of the stem parts of Solanum lyratum Thunb.Yakugaku Zasshi,1981,101(3):275~279.
[7] Murakami K,Ezima H,Takaishi Y,et al.Studies on the constituents of Solanum Plants.Ⅴ.The constituents of Solanum lyratum ThunbⅡ.Chem Pharm Bull,1985,33(1):67~73.
[8] Yung-yung Lee.Studies on the Solanum lyratum.Chem Bull,1997,45(8):1381~1382.
[9]杨敬芝,郭贵明,周立新,等.白英化学成分的研究.中国中药杂志,2002,27(1):42~43.
[10]徐顺,王林江,李瑞玲,等.白英全草中挥发油化学成分分析.时珍国医国药,2006,17(8):1390~1391.
[11] Kang SY,Sung SH,Park JH,et al.Hepatoprotective activity of scopoletin, a constituent of Solanum lyratum.Archives of Pharmacal Research,1998,21(6):718~722.
[12] Yu SM,Kim HJ,Woo JH,et al.Some sesquiterpenoids and 5α,8α-epidioxy-sterols from Solanum lyratum.Archives of Pharmacal Research,1994,17(1):1.
[13]佐藤昭彦.新しぃ抗が生药の探究されゐ汉方用生药の作用.汉方研究,1979,2:11~22.
[14]曹济远,谭湘陵.抗癌中药白毛藤对CHO细胞G2-PC染色体畸变的观察.现代应用药学,1988,5(6):1~3.
[15]施文荣,刘艳.白英对人急性早幼粒细胞白血病HL-60细胞生长的影响.福建中医学院学报,2002,12(1):36-38.
[16]单长民,胡娟娟,杜冠华.白英提取物诱导人肝癌BEL-7404细胞凋亡作用.中国临床药理学与治疗学,2001,6(3):200~203.
[17]任靖,冯国楠,王敏伟,等.白英总苷抗肿瘤作用初步研究.肿瘤防治研究,2006,33(4):262~264.
[18]任靖,冯国楠,王敏伟,等.白英乙醇提取物抗肿瘤作用初步研究.中国中药杂志,2006,31(6):497~500.
[19]孙立新,任靖,王敏伟,等.白英水提物抗肿瘤作用的初步研究.中草药,2006,37(1):98~100.
[20]涂硕.白英提取液诱导人肺癌A549细胞凋亡及其机制研究:[硕士学位论文].南昌:南昌大学,2006.
[21] Kim HM,Lee EJ.Solanum lyratum inhibits anaphylactic reaction and suppression of L-histidine decarboxylase mRNA.Immunopharmacology and Immunotoxicology,1998,20(1):135~146.
[22]谢永芳,廖系晗,梁亦龙,等.白英提取物的抗氧化作用研究.时珍国医国药,2006,17(6):899~900.
[23] Kim HM,Kim MJ,Li E,et al.The nitric oxide-producing properties of Solanum lyratum.Journal of Ethnopharmacology,1999,67(2):163~169.
[24]谢永芳,梁亦龙,舒坤贤,等.白英提取物的免疫调节作用研究.时珍国医国药,2007,18(2):386~387.
[25]张民庆.抗肿瘤中药的临床应用.北京:人民卫生出版社,1998,160.
[26]石晓兰.养阴清热解毒法治疗恶性肿瘤阴虚内热证临床研究.江苏中医药,2004,25(7):17.