清肺消痤颗粒的研制
摘要
痤疮是一种毛囊皮脂腺的慢性炎症性疾病,好发于颜面、胸背等皮脂溢出部位,在临床上极为多见,影响患者的生活、工作及身心健康。研制和开发治疗痤疮的药物具有重大的经济效益和社会效益。
目前治疗痤疮的西药多为激素类或抗生素类药物,疗效与禁忌症以及毒副作用等问题并存,而清肺消痤颗粒是一种纯中药口服制剂,在临床有效处方的基础上加减而来的,本方由黄芩,丹参,赤芍,等九味中药组成。本制剂组方合理,配伍精当,用于治疗痤疮。本课题的具体研究内容如下:
(1)提取工艺研究采用4种提取物对炎症小鼠模型进行药效筛选试验,选取处方的初步提取条件。以丹参中丹参酮ⅡA和丹酚酸B含量为指标,研究丹参和浙贝母药材的乙醇提取工艺,先以乙醇浓度为考察因素,得到乙醇提取的最佳浓度,再以提取时间,乙醇用量和提取次数为考察因素,进行正交试验,选取丹参和浙贝母的最佳提取工艺;以黄芩苷含量,芍药苷含量,水提浸膏得率及正丁醇萃取得率为指标,采用正交试验设计,优选黄芩等药的水提工艺;以黄芩苷含量,芍药苷含量及浸膏得率为指标,采用单因素试验设计,优选黄芩等群药水提液的精制工艺;以黄芩苷、芍药苷、丹参酮ⅡA和丹酚酸B含量为指标,对醇提液的浓缩进行考察。
(2)成型工艺研究通过对辅料用量、浸膏的相对密度以及一步制粒设备的有关参数进行考察,确定相关的工艺及技术参数。
(3)质量标准研究采用TLC法鉴别了制剂中黄芩、赤芍、连翘等九味药材,结果表明薄层色谱斑点清晰,分离度好,阴性无干扰,适用于清肺消痤颗粒的定性鉴别。采用HPLC法对测定了制剂中黄芩苷的含量,试验结果表明,黄芩苷的线性,精密度,重复性,加样回收率均良好,初步确定清肺消痤颗粒中含黄芩苷含量不低于20mg/g。
(4)稳定性考察采用留样观察法对制剂的定性鉴别、含量测定、水分、装量差异、微生物限度进行3个月的考察,结果均无明显变化,表明本品在考察期内稳定性良好。
(5)药效学研究初步药效学试验表明,清肺消痤颗粒具有缩小皮脂腺、降低血清睾酮水平、升高血清雌二醇水平的作用。
研究结果表明,清肺消痤颗粒制备工艺合理,质量稳定,稳定性良好,药效显著。
Acne is the inflammatory disease of sebaceous follicles,and located primarily on the face, back and chest,where there are more sebaceous glands.Acne is common in clinic,which impacts people's health,work and lives.Developing the medicine curing acne will have social and economical returns.
The western medicine of treating ance includes hormone and antibiotic medicine.The effect and side effect coexistent.Qingfei Xiaocuo granule is a kind of oral preparation composed of Traditional Chinese Medicine(TCM).It developed from effective prescription of TCM after properly disposed according to pharmacological and clinical practices.The granule is prepared by extracts from nine kinds of TCM.The preparation is organized reasonable and used to cure ance.The main research contents are as follows.
A.The preparation procedure The preliminary extraction technology was chosen by pharmacodynamic screening test of four different extract in mice inflammatory model. Orthogonal test was employed for selecting the optimum of extraction technology by the indexes of the contests of tanshinoneⅡA and lithospermate B of the Radix salviae miltiorrhizae and Fritillaria thunbergii Miq after studying the optimum alcohol concentration.Orthogonal test was also employed to select optical extraction technology of the Scutellaria baicalensis Georgi and other herbs with dregs of the Radix salviae miltiorrhizae and Fritillaria thnnbergii Miq applying comprehensive score by the indexes of the contests of baicalin,paeoniflorin,ratio of water extract immersing paste and n-butanol extracting.And the contests of baicalin and paeoniflorin were also used to investigate the purification technology of water extraction.The concentrated technology of ethanol extraction was by the contests of tanshinoneⅡA,lithospermate B,baicalin and paeoniflorin.
B.Forming procedure The granule was prepared by one-step palletizing.
C.Quality standard The medical materials contained in Qingfei Xiaocuo granule was identified by TLC;The quality identification by TLC was specific,having a good separation and a clear spot in each thin layer plate.The content of baicalin in this preparation was determined by HPLC in the study of quality standard.The experimental results suggest that their linearity,precision, reproducibility,recovery are all satisfactory.The content of baicalin was no less than 20mg/g.
D.The stability research The preparation character outward appearance,the load difference,the disintegration time limit,the moisture content determination,the microorganism limit,the qualitative distinction,the content determination item should be testified by sample preserved at room temperature.The test had been continuous carried out on for 3 months.The results didn't obviously change;It shows that the preparation was stable in the storage time,the stability was good.
E.Pharmacodynamic Study Pharmacodynamie test showed that Qingfei Xiaocuo granule has the effect of reducing sebaceous patches,lowering T levels and improving E2 levels of Golden Hamster.
The results show that the preparation procedure of Qingfei Xiaocuo is reasonable in technics,controllable in quality,good in stability,exat in effect.
目前治疗痤疮的西药多为激素类或抗生素类药物,疗效与禁忌症以及毒副作用等问题并存,而清肺消痤颗粒是一种纯中药口服制剂,在临床有效处方的基础上加减而来的,本方由黄芩,丹参,赤芍,等九味中药组成。本制剂组方合理,配伍精当,用于治疗痤疮。本课题的具体研究内容如下:
(1)提取工艺研究采用4种提取物对炎症小鼠模型进行药效筛选试验,选取处方的初步提取条件。以丹参中丹参酮ⅡA和丹酚酸B含量为指标,研究丹参和浙贝母药材的乙醇提取工艺,先以乙醇浓度为考察因素,得到乙醇提取的最佳浓度,再以提取时间,乙醇用量和提取次数为考察因素,进行正交试验,选取丹参和浙贝母的最佳提取工艺;以黄芩苷含量,芍药苷含量,水提浸膏得率及正丁醇萃取得率为指标,采用正交试验设计,优选黄芩等药的水提工艺;以黄芩苷含量,芍药苷含量及浸膏得率为指标,采用单因素试验设计,优选黄芩等群药水提液的精制工艺;以黄芩苷、芍药苷、丹参酮ⅡA和丹酚酸B含量为指标,对醇提液的浓缩进行考察。
(2)成型工艺研究通过对辅料用量、浸膏的相对密度以及一步制粒设备的有关参数进行考察,确定相关的工艺及技术参数。
(3)质量标准研究采用TLC法鉴别了制剂中黄芩、赤芍、连翘等九味药材,结果表明薄层色谱斑点清晰,分离度好,阴性无干扰,适用于清肺消痤颗粒的定性鉴别。采用HPLC法对测定了制剂中黄芩苷的含量,试验结果表明,黄芩苷的线性,精密度,重复性,加样回收率均良好,初步确定清肺消痤颗粒中含黄芩苷含量不低于20mg/g。
(4)稳定性考察采用留样观察法对制剂的定性鉴别、含量测定、水分、装量差异、微生物限度进行3个月的考察,结果均无明显变化,表明本品在考察期内稳定性良好。
(5)药效学研究初步药效学试验表明,清肺消痤颗粒具有缩小皮脂腺、降低血清睾酮水平、升高血清雌二醇水平的作用。
研究结果表明,清肺消痤颗粒制备工艺合理,质量稳定,稳定性良好,药效显著。
Acne is the inflammatory disease of sebaceous follicles,and located primarily on the face, back and chest,where there are more sebaceous glands.Acne is common in clinic,which impacts people's health,work and lives.Developing the medicine curing acne will have social and economical returns.
The western medicine of treating ance includes hormone and antibiotic medicine.The effect and side effect coexistent.Qingfei Xiaocuo granule is a kind of oral preparation composed of Traditional Chinese Medicine(TCM).It developed from effective prescription of TCM after properly disposed according to pharmacological and clinical practices.The granule is prepared by extracts from nine kinds of TCM.The preparation is organized reasonable and used to cure ance.The main research contents are as follows.
A.The preparation procedure The preliminary extraction technology was chosen by pharmacodynamic screening test of four different extract in mice inflammatory model. Orthogonal test was employed for selecting the optimum of extraction technology by the indexes of the contests of tanshinoneⅡA and lithospermate B of the Radix salviae miltiorrhizae and Fritillaria thunbergii Miq after studying the optimum alcohol concentration.Orthogonal test was also employed to select optical extraction technology of the Scutellaria baicalensis Georgi and other herbs with dregs of the Radix salviae miltiorrhizae and Fritillaria thnnbergii Miq applying comprehensive score by the indexes of the contests of baicalin,paeoniflorin,ratio of water extract immersing paste and n-butanol extracting.And the contests of baicalin and paeoniflorin were also used to investigate the purification technology of water extraction.The concentrated technology of ethanol extraction was by the contests of tanshinoneⅡA,lithospermate B,baicalin and paeoniflorin.
B.Forming procedure The granule was prepared by one-step palletizing.
C.Quality standard The medical materials contained in Qingfei Xiaocuo granule was identified by TLC;The quality identification by TLC was specific,having a good separation and a clear spot in each thin layer plate.The content of baicalin in this preparation was determined by HPLC in the study of quality standard.The experimental results suggest that their linearity,precision, reproducibility,recovery are all satisfactory.The content of baicalin was no less than 20mg/g.
D.The stability research The preparation character outward appearance,the load difference,the disintegration time limit,the moisture content determination,the microorganism limit,the qualitative distinction,the content determination item should be testified by sample preserved at room temperature.The test had been continuous carried out on for 3 months.The results didn't obviously change;It shows that the preparation was stable in the storage time,the stability was good.
E.Pharmacodynamic Study Pharmacodynamie test showed that Qingfei Xiaocuo granule has the effect of reducing sebaceous patches,lowering T levels and improving E2 levels of Golden Hamster.
The results show that the preparation procedure of Qingfei Xiaocuo is reasonable in technics,controllable in quality,good in stability,exat in effect.
引文
[1]Cunliffe WJ.The sebaceous gland and acne 40 years on.Dermatology,1998,196(1):9-15.
[2]姜春明,葛蒙梁.痤疮的发病机制以及研究进展[J]J Dermatology and Venereology,2003,3(25):16:19.
[3]靳培英.痤疮的分型论治[J].中华皮肤科杂志,2002,35(1):67-69.
[4]施伟民,陈德利,朴莫兰,等.痤疮患者血清性激素水平的研究[J].临床皮肤科杂志,1998,27(1):15-16.
[5]范瑞强,何盛供,张国维.66例痤疮患者血清睾酮及雌二醇水平研究[J].临床皮肤科杂志.1998,27(1):17-18.
[6]曾燕,张素芳,李韧,等.13-顺维甲酸对痤疮患者AR的影响[J].中华医学美容杂志,2001,7(1):17-18.
[7]曾燕,卢建,张金山,等.雄激素对正常男性及一睾丸女性化综合征患者外阴部皮肤成纤维细胞AR 的调节[J].中国病理生理杂志,1994,10:276-279.
[8]姜春明,葛蒙梁.痤疮发病机制研究进展[J].皮肤病与性病,2003,25(1):16-18.
[9]曾燕.痤疮患者外周血白细胞雄激素受体的测定[J].中华皮肤科杂志,1999,32(4):131.
[10]弓娟琴,故兹嘉.痤疮与雄激素关系的研究进展[J].国外医学皮肤性病学分册,1997,23(1):65.
[11]Cunliffe WJ,Holland DB,Clarl SM,et al.Comedogenesis:some new aetiological,clinical and therapeutic strategies.Br J Dermatol,2000;142:1084-1091.
[12]王大光.痤疮发病中毛囊皮脂腺导管异常角质化的机制[J].中国麻风皮肤病杂志,2005,1(23):36-37.
[13]Harald Gollnick MD,Willian Cunliffe MD,FRCP.Management of ache:A report from a global alliance to improve outcomes in acne.J Am Acad Dermatol,2003,49:2-5.
[14]Thiboutot DM,KnaggsH,Gilliland K,et al.Activity of type I 5a-reductase is greater in the follicular infundibulum compated with theepidermis.Br J Dermatol 1997;136:166-171.
[15]Ingham E,Eaby EA,Goodwin CE,et al.Pro-inflammatory levels of interleuldn-la-like bioactivity are present in the majority of open comedones in ache vulgaris[J].Invest Dermatol,1992,98(6):895-901
[16]鞠强,石继海,夏隆庆.白介素-1与痤疮[J].国外医学皮肤性病学分册,2001,27(1):24-26
[17]Anthony H.T.Jeremy,Diana B.Holland,Susan GRoberts,lnflammatory events are involved in ache lesion initiation[J].The Journal of Investigative Dermatology,2003,121(1):20-27
[18]Paraskevaidis A,Drakoulis N.Polymorphisms in the human cytochrome P450 Ⅰ A1 gene as a factor for developing acne[J].Dermatology Basel,1998,196(1):171-175.
[19]王建萍,曾仁山,唐韶生.女性寻常性痤疮患者免疫球蛋白补体及可溶性IL-2R的检测[J].中国皮肤性病学杂志,2002,16(2):79-81.
[20]杨日东,林泽.痤疮皮损的免疫细胞化学分析[J].中国皮肤性病学杂志,1993.11(4)209-210.
[21]Hornemannn S,Seltmann H,Kodelia V,et al.Intedeukin lamRNA and protein are expressed in cultured human sebocytes at steady-state and their levels are barely influnced by lipopolysaccharides[J].J Invest Dermatol,1997,108:382.
[22]Zal μga Elzbieta.Skin reactions to antigens of Propionibacterium aches in patients with ache vulgaris treated with autovaccine[J].Roczniki Pomorskiej Akademii Medycznej W Szczecinie,1998,44:65-85.
[23]吴小红等.痤疮发病机理的中西医研究现状[J].中国中西医结合皮肤性病学杂志,2003,3(2):193.197
[24]Nishijima S,Kurokawal,Katoh N,et al.The bacteriology of acne vulgaris antimicrobial susceptibility of Propionibacterium aches and Staphylococcus epidermidis isolated from ache lesions[J].J Dermatol,2000,27(5):318-323.
[25]靳培英.痤疮的分型论治[J].中华皮肤科杂志,2002,35(1):67-69.
[26]鞠强,石继海,夏隆庆.白介素-1与痤疮.国外医学.皮肤性病学分册,2001,27(1):24-26.
[27]昝文华,李艳红,徐泊文,等.寻常痤疮患者与正常人面部皮肤葡萄球菌种类的对比研究.Clin Dermatol,2001,30(2):98.
[28]SagiE.The combination for mulation of 2%erythromycinplus 1%bionazole once a day versus for mulations of topical 2%erythromycin alonetwice a day in the treatment of ache vulgaris.Arandomandblindstudy.J DermatolTreat,2000,11(4):247-251.
[29]杨智,何黎.痤疮与遗传.国外医学皮肤性病学分册,2005,31(1):33-34.
[30]张爱清,李克华,王甘棠,等.痤疮患者个性特征及情绪反应的研究冲国皮肤性病学杂志,1997,13(1):17.
[31]蔡能,史鸿璋,陈钟舜,等.心身病。上海:上海科技文献出版社,1985,88.
[32]虞瑞尧.痤疮诊断彩色图谱.北京:北京科学技术出版社,2001.
[33]王侠生,廖康煌.杨国亮皮肤病学[M],上海:上海科学技术文献出版社,2005:725-728.
[34]卢俊明,吴小山,马志舜,等.中西药合用治疗丘疹座疮56例.实用中医药杂志[J],2002,18(5):28.
[35]虞瑞小.痤疮的防与治.药物与人[J],1997.10(6):31.
[36]陈信生.范瑞强教授论治痤疮经验[J].新中医.2001.33(9):71-72.
[37]张素洁.中医药治疗痤疮的信息分析与思索[J]中国中医药信息杂志,1998,(1):38.
[38]陈英.女子面部痤疮从肝论治河北中医[J].2003,25(2):110.
[39]张爱清,李克华,王甘棠,等.座疮患者个性特征及情绪反应的研究.中国皮肤性病学杂志,1999:13(1):17.
[40]李卓然,丰全德,高金红,中年妇女面部座疮德分型施治[J]中国美容医学.2001.10(2):111.
[41]陈英.女子面部座疮从肝论治[J].河北中医.2003.25(2):110-111.
[42]郭青海。单味丹参饮治疗座疮160例[J].吉林中医药.2006,26(9):41.
[43]黄畋,孔俐君,孔令,等.48种中药对痤疮丙酸杆菌的抑制作用[J]中华皮肤科杂志,1992,(5):307.
[44]吕世静,黄槐莲.丹参注射液的免疫药理作用[J]中国临床免疫学杂志,1992,(2):41.
[45]欧阳瑜,尚京川,付渝滨.大黄素对白三烯B4和前列腺素E2生物合成的影响[J]中国药理与临床,1991,(5):12.
[46]赵炳南,张志礼.简明中医皮肤病学.北京:中国展望出版社,1983,238.
[47]张志礼.皮肤科手册.北京:中医古籍出版社,2004,472-473.
[48]周德瑛,李映琳,金起凤.老中医清热凉血法治疗皮肤病经验举隅.中医教育,1994,(2):36.
[49]徐爱琴.徐宜厚诊疗痤疮经验.中医杂志,1998,(2):80.
[50]中医研究院广安门医院编.朱仁康临床经验集.北京:人民卫生出版社,1986,197.
[51]华华.薛伯寿教授治疗痤疮的中医辨证体会.中医药学报,2005,33(6):37.
[52]阙华发.陆德铭治痤疮经验撷萃.江西中医药,1997(3):7.
[53]陶国水.顾植山辨治痤疮5法.安徽中医临床杂志,2002,14(3):204.
[54]禤国维.皮肤病临证见解.新中医,1996,28(1):14.
[55]张曦,李宏,侯茂君,等.黄芩及其有效成分的药理学研究进展[J].天津药学.2000,12(4):8-11.
[56]孟申.中药有效成分抗氧化作用的实验研究[J].中国药理学通报,1992,8(5):326-330.
[57]张健.黄芩甙、茜草素、茶多酚和Trolox抗氧化能力的增强化学发光的研究[J].生物物理学报,1996,12(2):350-356.
[58]谭廷华.丁香酚对氧自由基的清除作用[J].西北药学杂志,1996,11(1):30-31.
[59]Konoshima T et al.Chem-Pharm-Bull-Tokyo,1992,40(2):531-533.
[60]贺海平.国外医学中医药分册[J].2000,22(1):14-16.
[61]周晓红,甄彦君,冯敬坤.黄芩研究进展[J]河北中医药学报,2000,3(15):31.
[62]刘云波,郭丽华,邱世翠,等.黄芩体外抑菌作用研究.时珍国医国药,2002,13(10):596.
[63]邝枣园,黄衍寿,吴伟,等.黄芩苷对肺炎衣原体诱导的内皮细胞粘附因子表达的影响.广州中医药大学学报,2004,21(6):454.
[64]邝枣园,黄衍寿,吴伟.黄芩苷对肺炎衣原体诱导的可溶性细胞粘附因子及IL-8的影响.浙江中医杂志,2004,9(11):502.
[65]赵晶.黄芩甙元及其苄基衍生物的制备与抗人免疫缺陷病毒实验研究[J].药学学报,1997,32(2):14-143.
[66]蒋锡源.50种治疗肝炎中草药与制剂体外抑制HBcAg活性的比较[J].现代应用药学,1992,9(5):208.
[67]尹飞,杨于嘉,虞佩兰,等.黄芩甙对百日咳菌液致离体大鼠脑组织损害的保护作用及量效关系的研究[J1.中国中西医结合杂志,2002,22(4):286-288.
[68]陈忻,董晓丹,张楠,等.黄芩苷对局灶性脑缺血模型大鼠的保护作用.广州中医药大学学报,2006,23(6):506-508.
[69]Shinichi Ikemoto,Kaiunobu S μgimuka,Naomasa Yoshida,et al.Anxiolytie-like effects of baicalein and baicalin in the vogel conflict testin mice.Eur J Pharmacal,2003,464(2):141-146.
[70]张小伟,张会敏,石俊英.近五年黄芩药理学研究进展[J].齐鲁药事,2008,(3):165-167.
[71]Zhou GY,Zhao BL,Hou JW,et al.Protective effects of sodium ta nshinone Ⅱ,Asulphonate against adriamycin-induced lipid peroxidation in mice hearts in vivo and in vitro[J]Pharmacol Res,1999,40(6):487.
[72]谷雨,谷巍,于淑莲.丹参药理作用研究进展[J].人参研究,2007,1:25-27.
[73]胡世林,付桂兰,冯学锋等.不同产地和部位赤芍中芍药苷的含量测定[J].中国中药杂志,2000,25(12):714-716.
[74]杨嫒嫒,周刚,马小康,等.赤芍的研究进展[J].医药导报,2008,27(1):67-69.
[75]徐先祥,夏伦祝,高家荣,等.黄芪总苷和赤芍总苷协同抗血小板作用研究[J].中药材,2002,25 (9):653-655.
[76]杨大国,王林杰,宋为云,等.重用赤芍治疗慢性肝炎纤维化前后肝组织学的比较[J].中国中西医结合杂志,1994,14(4):207-209.
[77]张永艳,赵文霞.赤芍防治肝病的作用及机制研究[J].陕西中医,2003,24(7):655-656.
[78]胡梅雪.活血化瘀法治疗肝纤维化[J].中医药学报,1998,19(2):13.
[79]中华本草编委会.中华本草[M].上册.上海:上海科学技术出社,1998.338.
[80]薛岚.中药虎杖的药理研究进展[J]冲国中药杂志,2000,25(11):653。
[81]中国人民解放军广字173部队化学教研室、药理教研室.复方阴阳莲的实验研究.新医学杂志,1973,12:31.
[82]木岛正夫,等.药用植物大辞典(日).广川书店,1977,28.
[83]金航.虎杖抗HFVI活性的体外实验研究.国外医学.中医中药分册,1995;17(3):32
[84]周立东,等.虎杖煎剂对艾氏腹水癌的抑瘤作用[J].中西医结合杂志,1989,9(2):111.
[85]尹梅,常胜军.煎煮条件对连翘中卢丁成份提取量的影响[J].新疆中医药,2002,20(2):11-12.
[86]张海燕.连翘化学成分及药理活性的研究进展[J].中药材,2000,13(10):660.
[87]薛燕,顾好粮.HPLC-ELSD法测定浙贝母中主要生物碱的含量[J].药学学报 2005,40(6):550-552.
[88]张明发,沈亚琴.浙贝母药理研究进展[J].上海医药,2007,28(10):459.
[89]吴梅青,刘佳佳.桔梗化学成分研究进展[J].黑龙江医药,2007,20(5):443-446.
[90]宋杨,齐云.桔梗的药理研究进展[J].中国药房,2006,17(2):140-141.
[91]国家中医药管理局《中华本草》编委会.中华本草(精选本).上册[M].上海:上海科技出版社,1998:740.
[92]林小明,桃仁化学成分和药理作用研究进展[J].蛇志,2007,19(2):131-132.
[93]高学敏.中药学[M]北京:中国中医药出版社,2002.9:313.
[94]国家药典委员会.中华人民共和国药典(一部)[S]2005年版,北京:化学工业出版社,2005:52.
[95]国家药典委员会.中华人民共和国药典(一部)[s]2005年版,北京:化学工业出版社,2005:109.
[96]潘英.中药制粒工艺的发展状况[J].中医药学刊,2004,22(4):765
[97]张为亮,冯建,李美林,等.全面采用一步制粒技术,提高中药工业水平[J]中国中药杂志,2008,33(1):98-99.
[98]元清,严建业,杨红艳.喷雾干燥技术及其在中药制剂中的应用[J].时珍国医国药,2005,15(2):161.
[99]潘强,王世岭,贾立华.喷雾干燥制备康复欣胶囊颗粒的影响因素[J1.中国药业,2004,13(3):52-53.
[100]陆彬.中药颗粒剂处方组成的探讨.华西医学杂志,1995;10(4):229-233.
[101]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:附录Ⅰ C、ⅦC.
[102]康纯,闻莉毓,丁仲伯.微乳薄层色谱用于黄酮类成分分离鉴定的研究[J]药物分析,2000,2(20):121.
[103]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:145.
[104]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:601,218,643,142.
[105]申欣,查娅妮.风热感冒颗粒质量标准研究[J].中国药业,2008,17(9):25-26.
[106]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:196.
[107]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:山楂.
[108]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:140.
[109]王建明,王岩松,马晓星,等.乳康胶囊的TLC鉴别及含量测定[J]冲国中医药信息杂志,2008,15(3):49-51.
[110]张喜平,田华,程琪辉.黄芩苷的药理研究现状[J]中国药理学通报,2003,19(11),1212-1215.
[111]闫玉冰,杨东岩,李晓英,等.HPLC法测定黄芩素铝胶囊中黄芩苷[J]国外医药·植物药分册,2007,22(5):206.
[111]张湛睿,李巧如,杜洪霞,等.HPLC法测定炎热清胶囊中黄芩苷的含量[J]中国药房,2007,18(36):2847-2848.
[112]曾晓瑜,贺英菊,李建萍,等.高效液相色谱法测定一枝黄花抗感颗粒中黄芩苷含量[J]中国药业,2008,17(5):16-17.
[113]周展超,郑家润,徐文严.安体舒通及丹参酮抗金黄地鼠皮脂腺斑增生的研究[J]中华皮肤科杂志.1997.30(31):182.
[2]姜春明,葛蒙梁.痤疮的发病机制以及研究进展[J]J Dermatology and Venereology,2003,3(25):16:19.
[3]靳培英.痤疮的分型论治[J].中华皮肤科杂志,2002,35(1):67-69.
[4]施伟民,陈德利,朴莫兰,等.痤疮患者血清性激素水平的研究[J].临床皮肤科杂志,1998,27(1):15-16.
[5]范瑞强,何盛供,张国维.66例痤疮患者血清睾酮及雌二醇水平研究[J].临床皮肤科杂志.1998,27(1):17-18.
[6]曾燕,张素芳,李韧,等.13-顺维甲酸对痤疮患者AR的影响[J].中华医学美容杂志,2001,7(1):17-18.
[7]曾燕,卢建,张金山,等.雄激素对正常男性及一睾丸女性化综合征患者外阴部皮肤成纤维细胞AR 的调节[J].中国病理生理杂志,1994,10:276-279.
[8]姜春明,葛蒙梁.痤疮发病机制研究进展[J].皮肤病与性病,2003,25(1):16-18.
[9]曾燕.痤疮患者外周血白细胞雄激素受体的测定[J].中华皮肤科杂志,1999,32(4):131.
[10]弓娟琴,故兹嘉.痤疮与雄激素关系的研究进展[J].国外医学皮肤性病学分册,1997,23(1):65.
[11]Cunliffe WJ,Holland DB,Clarl SM,et al.Comedogenesis:some new aetiological,clinical and therapeutic strategies.Br J Dermatol,2000;142:1084-1091.
[12]王大光.痤疮发病中毛囊皮脂腺导管异常角质化的机制[J].中国麻风皮肤病杂志,2005,1(23):36-37.
[13]Harald Gollnick MD,Willian Cunliffe MD,FRCP.Management of ache:A report from a global alliance to improve outcomes in acne.J Am Acad Dermatol,2003,49:2-5.
[14]Thiboutot DM,KnaggsH,Gilliland K,et al.Activity of type I 5a-reductase is greater in the follicular infundibulum compated with theepidermis.Br J Dermatol 1997;136:166-171.
[15]Ingham E,Eaby EA,Goodwin CE,et al.Pro-inflammatory levels of interleuldn-la-like bioactivity are present in the majority of open comedones in ache vulgaris[J].Invest Dermatol,1992,98(6):895-901
[16]鞠强,石继海,夏隆庆.白介素-1与痤疮[J].国外医学皮肤性病学分册,2001,27(1):24-26
[17]Anthony H.T.Jeremy,Diana B.Holland,Susan GRoberts,lnflammatory events are involved in ache lesion initiation[J].The Journal of Investigative Dermatology,2003,121(1):20-27
[18]Paraskevaidis A,Drakoulis N.Polymorphisms in the human cytochrome P450 Ⅰ A1 gene as a factor for developing acne[J].Dermatology Basel,1998,196(1):171-175.
[19]王建萍,曾仁山,唐韶生.女性寻常性痤疮患者免疫球蛋白补体及可溶性IL-2R的检测[J].中国皮肤性病学杂志,2002,16(2):79-81.
[20]杨日东,林泽.痤疮皮损的免疫细胞化学分析[J].中国皮肤性病学杂志,1993.11(4)209-210.
[21]Hornemannn S,Seltmann H,Kodelia V,et al.Intedeukin lamRNA and protein are expressed in cultured human sebocytes at steady-state and their levels are barely influnced by lipopolysaccharides[J].J Invest Dermatol,1997,108:382.
[22]Zal μga Elzbieta.Skin reactions to antigens of Propionibacterium aches in patients with ache vulgaris treated with autovaccine[J].Roczniki Pomorskiej Akademii Medycznej W Szczecinie,1998,44:65-85.
[23]吴小红等.痤疮发病机理的中西医研究现状[J].中国中西医结合皮肤性病学杂志,2003,3(2):193.197
[24]Nishijima S,Kurokawal,Katoh N,et al.The bacteriology of acne vulgaris antimicrobial susceptibility of Propionibacterium aches and Staphylococcus epidermidis isolated from ache lesions[J].J Dermatol,2000,27(5):318-323.
[25]靳培英.痤疮的分型论治[J].中华皮肤科杂志,2002,35(1):67-69.
[26]鞠强,石继海,夏隆庆.白介素-1与痤疮.国外医学.皮肤性病学分册,2001,27(1):24-26.
[27]昝文华,李艳红,徐泊文,等.寻常痤疮患者与正常人面部皮肤葡萄球菌种类的对比研究.Clin Dermatol,2001,30(2):98.
[28]SagiE.The combination for mulation of 2%erythromycinplus 1%bionazole once a day versus for mulations of topical 2%erythromycin alonetwice a day in the treatment of ache vulgaris.Arandomandblindstudy.J DermatolTreat,2000,11(4):247-251.
[29]杨智,何黎.痤疮与遗传.国外医学皮肤性病学分册,2005,31(1):33-34.
[30]张爱清,李克华,王甘棠,等.痤疮患者个性特征及情绪反应的研究冲国皮肤性病学杂志,1997,13(1):17.
[31]蔡能,史鸿璋,陈钟舜,等.心身病。上海:上海科技文献出版社,1985,88.
[32]虞瑞尧.痤疮诊断彩色图谱.北京:北京科学技术出版社,2001.
[33]王侠生,廖康煌.杨国亮皮肤病学[M],上海:上海科学技术文献出版社,2005:725-728.
[34]卢俊明,吴小山,马志舜,等.中西药合用治疗丘疹座疮56例.实用中医药杂志[J],2002,18(5):28.
[35]虞瑞小.痤疮的防与治.药物与人[J],1997.10(6):31.
[36]陈信生.范瑞强教授论治痤疮经验[J].新中医.2001.33(9):71-72.
[37]张素洁.中医药治疗痤疮的信息分析与思索[J]中国中医药信息杂志,1998,(1):38.
[38]陈英.女子面部痤疮从肝论治河北中医[J].2003,25(2):110.
[39]张爱清,李克华,王甘棠,等.座疮患者个性特征及情绪反应的研究.中国皮肤性病学杂志,1999:13(1):17.
[40]李卓然,丰全德,高金红,中年妇女面部座疮德分型施治[J]中国美容医学.2001.10(2):111.
[41]陈英.女子面部座疮从肝论治[J].河北中医.2003.25(2):110-111.
[42]郭青海。单味丹参饮治疗座疮160例[J].吉林中医药.2006,26(9):41.
[43]黄畋,孔俐君,孔令,等.48种中药对痤疮丙酸杆菌的抑制作用[J]中华皮肤科杂志,1992,(5):307.
[44]吕世静,黄槐莲.丹参注射液的免疫药理作用[J]中国临床免疫学杂志,1992,(2):41.
[45]欧阳瑜,尚京川,付渝滨.大黄素对白三烯B4和前列腺素E2生物合成的影响[J]中国药理与临床,1991,(5):12.
[46]赵炳南,张志礼.简明中医皮肤病学.北京:中国展望出版社,1983,238.
[47]张志礼.皮肤科手册.北京:中医古籍出版社,2004,472-473.
[48]周德瑛,李映琳,金起凤.老中医清热凉血法治疗皮肤病经验举隅.中医教育,1994,(2):36.
[49]徐爱琴.徐宜厚诊疗痤疮经验.中医杂志,1998,(2):80.
[50]中医研究院广安门医院编.朱仁康临床经验集.北京:人民卫生出版社,1986,197.
[51]华华.薛伯寿教授治疗痤疮的中医辨证体会.中医药学报,2005,33(6):37.
[52]阙华发.陆德铭治痤疮经验撷萃.江西中医药,1997(3):7.
[53]陶国水.顾植山辨治痤疮5法.安徽中医临床杂志,2002,14(3):204.
[54]禤国维.皮肤病临证见解.新中医,1996,28(1):14.
[55]张曦,李宏,侯茂君,等.黄芩及其有效成分的药理学研究进展[J].天津药学.2000,12(4):8-11.
[56]孟申.中药有效成分抗氧化作用的实验研究[J].中国药理学通报,1992,8(5):326-330.
[57]张健.黄芩甙、茜草素、茶多酚和Trolox抗氧化能力的增强化学发光的研究[J].生物物理学报,1996,12(2):350-356.
[58]谭廷华.丁香酚对氧自由基的清除作用[J].西北药学杂志,1996,11(1):30-31.
[59]Konoshima T et al.Chem-Pharm-Bull-Tokyo,1992,40(2):531-533.
[60]贺海平.国外医学中医药分册[J].2000,22(1):14-16.
[61]周晓红,甄彦君,冯敬坤.黄芩研究进展[J]河北中医药学报,2000,3(15):31.
[62]刘云波,郭丽华,邱世翠,等.黄芩体外抑菌作用研究.时珍国医国药,2002,13(10):596.
[63]邝枣园,黄衍寿,吴伟,等.黄芩苷对肺炎衣原体诱导的内皮细胞粘附因子表达的影响.广州中医药大学学报,2004,21(6):454.
[64]邝枣园,黄衍寿,吴伟.黄芩苷对肺炎衣原体诱导的可溶性细胞粘附因子及IL-8的影响.浙江中医杂志,2004,9(11):502.
[65]赵晶.黄芩甙元及其苄基衍生物的制备与抗人免疫缺陷病毒实验研究[J].药学学报,1997,32(2):14-143.
[66]蒋锡源.50种治疗肝炎中草药与制剂体外抑制HBcAg活性的比较[J].现代应用药学,1992,9(5):208.
[67]尹飞,杨于嘉,虞佩兰,等.黄芩甙对百日咳菌液致离体大鼠脑组织损害的保护作用及量效关系的研究[J1.中国中西医结合杂志,2002,22(4):286-288.
[68]陈忻,董晓丹,张楠,等.黄芩苷对局灶性脑缺血模型大鼠的保护作用.广州中医药大学学报,2006,23(6):506-508.
[69]Shinichi Ikemoto,Kaiunobu S μgimuka,Naomasa Yoshida,et al.Anxiolytie-like effects of baicalein and baicalin in the vogel conflict testin mice.Eur J Pharmacal,2003,464(2):141-146.
[70]张小伟,张会敏,石俊英.近五年黄芩药理学研究进展[J].齐鲁药事,2008,(3):165-167.
[71]Zhou GY,Zhao BL,Hou JW,et al.Protective effects of sodium ta nshinone Ⅱ,Asulphonate against adriamycin-induced lipid peroxidation in mice hearts in vivo and in vitro[J]Pharmacol Res,1999,40(6):487.
[72]谷雨,谷巍,于淑莲.丹参药理作用研究进展[J].人参研究,2007,1:25-27.
[73]胡世林,付桂兰,冯学锋等.不同产地和部位赤芍中芍药苷的含量测定[J].中国中药杂志,2000,25(12):714-716.
[74]杨嫒嫒,周刚,马小康,等.赤芍的研究进展[J].医药导报,2008,27(1):67-69.
[75]徐先祥,夏伦祝,高家荣,等.黄芪总苷和赤芍总苷协同抗血小板作用研究[J].中药材,2002,25 (9):653-655.
[76]杨大国,王林杰,宋为云,等.重用赤芍治疗慢性肝炎纤维化前后肝组织学的比较[J].中国中西医结合杂志,1994,14(4):207-209.
[77]张永艳,赵文霞.赤芍防治肝病的作用及机制研究[J].陕西中医,2003,24(7):655-656.
[78]胡梅雪.活血化瘀法治疗肝纤维化[J].中医药学报,1998,19(2):13.
[79]中华本草编委会.中华本草[M].上册.上海:上海科学技术出社,1998.338.
[80]薛岚.中药虎杖的药理研究进展[J]冲国中药杂志,2000,25(11):653。
[81]中国人民解放军广字173部队化学教研室、药理教研室.复方阴阳莲的实验研究.新医学杂志,1973,12:31.
[82]木岛正夫,等.药用植物大辞典(日).广川书店,1977,28.
[83]金航.虎杖抗HFVI活性的体外实验研究.国外医学.中医中药分册,1995;17(3):32
[84]周立东,等.虎杖煎剂对艾氏腹水癌的抑瘤作用[J].中西医结合杂志,1989,9(2):111.
[85]尹梅,常胜军.煎煮条件对连翘中卢丁成份提取量的影响[J].新疆中医药,2002,20(2):11-12.
[86]张海燕.连翘化学成分及药理活性的研究进展[J].中药材,2000,13(10):660.
[87]薛燕,顾好粮.HPLC-ELSD法测定浙贝母中主要生物碱的含量[J].药学学报 2005,40(6):550-552.
[88]张明发,沈亚琴.浙贝母药理研究进展[J].上海医药,2007,28(10):459.
[89]吴梅青,刘佳佳.桔梗化学成分研究进展[J].黑龙江医药,2007,20(5):443-446.
[90]宋杨,齐云.桔梗的药理研究进展[J].中国药房,2006,17(2):140-141.
[91]国家中医药管理局《中华本草》编委会.中华本草(精选本).上册[M].上海:上海科技出版社,1998:740.
[92]林小明,桃仁化学成分和药理作用研究进展[J].蛇志,2007,19(2):131-132.
[93]高学敏.中药学[M]北京:中国中医药出版社,2002.9:313.
[94]国家药典委员会.中华人民共和国药典(一部)[S]2005年版,北京:化学工业出版社,2005:52.
[95]国家药典委员会.中华人民共和国药典(一部)[s]2005年版,北京:化学工业出版社,2005:109.
[96]潘英.中药制粒工艺的发展状况[J].中医药学刊,2004,22(4):765
[97]张为亮,冯建,李美林,等.全面采用一步制粒技术,提高中药工业水平[J]中国中药杂志,2008,33(1):98-99.
[98]元清,严建业,杨红艳.喷雾干燥技术及其在中药制剂中的应用[J].时珍国医国药,2005,15(2):161.
[99]潘强,王世岭,贾立华.喷雾干燥制备康复欣胶囊颗粒的影响因素[J1.中国药业,2004,13(3):52-53.
[100]陆彬.中药颗粒剂处方组成的探讨.华西医学杂志,1995;10(4):229-233.
[101]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:附录Ⅰ C、ⅦC.
[102]康纯,闻莉毓,丁仲伯.微乳薄层色谱用于黄酮类成分分离鉴定的研究[J]药物分析,2000,2(20):121.
[103]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:145.
[104]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:601,218,643,142.
[105]申欣,查娅妮.风热感冒颗粒质量标准研究[J].中国药业,2008,17(9):25-26.
[106]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:196.
[107]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:山楂.
[108]国家药典委员会.中华人民共和国药典[S].一部.北京:化学工业出版社,2005:140.
[109]王建明,王岩松,马晓星,等.乳康胶囊的TLC鉴别及含量测定[J]冲国中医药信息杂志,2008,15(3):49-51.
[110]张喜平,田华,程琪辉.黄芩苷的药理研究现状[J]中国药理学通报,2003,19(11),1212-1215.
[111]闫玉冰,杨东岩,李晓英,等.HPLC法测定黄芩素铝胶囊中黄芩苷[J]国外医药·植物药分册,2007,22(5):206.
[111]张湛睿,李巧如,杜洪霞,等.HPLC法测定炎热清胶囊中黄芩苷的含量[J]中国药房,2007,18(36):2847-2848.
[112]曾晓瑜,贺英菊,李建萍,等.高效液相色谱法测定一枝黄花抗感颗粒中黄芩苷含量[J]中国药业,2008,17(5):16-17.
[113]周展超,郑家润,徐文严.安体舒通及丹参酮抗金黄地鼠皮脂腺斑增生的研究[J]中华皮肤科杂志.1997.30(31):182.