水飞蓟素胶丸的制备及其含量测定

目的　制备水飞蓟素胶丸 ,建立测定胶丸中水飞蓟宾含量的方法。方法　水飞蓟素原料制成微粉 ,研磨乳化后制丸 ,并用HPLC测定主要成分水飞蓟宾的含量。结果　胶丸符合中国药典标准 ;胶丸中水飞蓟宾的含量为 6 2 .7mg·g-1,平均回收率为 97.5 % ,RSD =0 .80 % (n =6 )。结论　所制制剂工艺简单 ,有效成分的检测方法准确可靠。     

高效液相色谱法测定水飞蓟提取物中水飞蓟宾的含量

目的建立一种用反相高效液相色谱测定水飞蓟提取物中水飞蓟宾含量的方法。方法以Shim-packVP-ODS(250mm×4.6mm,5μm)为分析柱;以甲醇-水-乙腈-磷酸(45∶50∶5∶0.5,体积比)为流动相。结果测得平均回收率为102.3%,RSD为0.75%。结论方法准确可靠、简便,适用于水飞蓟提取物中水飞蓟宾的含量测定。     

RP-HPLC测定大鼠血浆中水飞蓟宾的浓度

目的　测定大鼠血浆中水飞蓟宾的浓度。方法　用RP -HPLC。样品以叔丁基甲醚提取 ,色谱柱为PoresphereC18柱 (4.0mm× 2 5 0mm ,5 μm) ,流动相为甲醇 水 0 .0 5mol·L-1磷酸二氢钾 (2 0∶10∶7) ,流速为 1.0ml·min-1,检测波长为 2 88nm ,温度为室温。结果　大鼠血浆中成分对水飞蓟宾的测定无干扰 ;在 0 .0 0 6 1～ 3.12 5 μg·ml-1浓度范围内呈现良好的线性关系 ,r=0 .9992 ;血浆中水飞蓟宾的最低检测浓度为 6ng·ml-1,平均回收率为10 7.0 0 % ,日内RSD≤ 8.19% ,日间RSD≤ 13.78%。结论　该法样品处理简便 ,灵敏度高 ,结果准确。     

反相高效液相色谱法测定人血浆中水飞蓟宾的浓度

目的 :建立测定人血浆中水飞蓟宾浓度的反相高效液相色谱法。方法 :血样在pH 8 5条件下经乙醚提取后 ,采用 μBondapakC18(30 0mm× 4 6mm)色谱柱 ,甲醇 -乙腈 -磷酸盐缓冲液 (pH 3 0 ) (2 9∶2 0∶5 1)为流动相 ,以萘酚为内标 ,检测波长 2 88nm。结果 :水飞蓟宾在 3 6 95～ 2 36 5ng·mL-1范围内线性相关 (r =0 9998) ,方法回收率为 96 5 % ,日内、日间RSD均小于 2 3% (n =3)。结论 :方法简便快速、灵敏度高 ,适用于该药的临床药理研究     

HPLC法同时测定水飞蓟果实不同部位及其提取物中水飞蓟亭等7种黄酮类成分的含量

目的建立水飞蓟果实、果皮、果仁及其提取物中花旗松素、水飞蓟亭、水飞蓟宁、水飞蓟宾A、水飞蓟宾B、异水飞蓟宾A和异水飞蓟宾B等7种黄酮类成分的含量测定方法。方法采用HPLC法,色谱柱为Kromasil C18(200 mm×4.6 mm,5μm)柱,以甲醇-水-甲酸为流动相,梯度洗脱,流速为1.0 m L·min-1,检测波长为288 nm,柱温为40℃,进样量为20μL。结果花旗松素、水飞蓟亭、水飞蓟宁、水飞蓟宾A、水飞蓟宾B、异水飞蓟宾A和异水飞蓟宾B的质量浓度分别在1.00~25.0、3.96~99.0、1.96~49.0、4.00~100、4.08~102、2.00~50.0和1.04~26.0 mg·L-1内与峰面积呈良好的线性关系(r≥0.999 0),平均加样回收率为96.4%~103.3%,RSD均小于3.1%。不同水飞蓟果实、果皮、果仁及提取物中7种成分含量及总水飞蓟素含量均显示出一定差异。结论本法可为水飞蓟药材及其提取物质量的综合评价提供准确的定量方法。     

水飞蓟素磷脂复合物家兔体内生物利用度的研究

进行了水飞蓟素磷脂复合物家兔体内的生物利用度研究。采用 HPL C法测定血浆中水飞蓟宾游离浓度和总浓度 ,结果显示在选定色谱条件下水飞蓟宾分离良好。水分蓟素原药与复合物服用后总药物浓度的药 -时曲线均出现双峰现象 ,AUC( 0～ 1 2 h) 分别为 5 .5 5和 11.95μg· m l- 1 · h- 1 ,Cmax分别为 0 .76± 0 .5 4、1.0 2± 0 .6 7和 1.6 3± 1.5 0、2 .75± 1.92 μg/ m l,Tmax分别为 1、4 h和 0 .5、2 h;给予水飞蓟素原药后游离药物的血药浓度低于检测限 ,给予复合物后游离药物的药 -时曲线也出现双峰现象 ,Cmax为 0 .99± 1.0 6、0 .35± 0 .31μg/ m l,Tmax为 0 .5、3h,AUC( 0～ 1 2 h) 为2 .4 8μg· ml- 1· h- 1。     

HPLC法测定水飞蓟素及制剂中水飞蓟宾的含量

目的：建立了利用简单流动相组成测定水飞蓟素及制剂中水飞蓟宾的高效液相色谱法。方法：色谱柱为Inertsil—C8（4．6mm×250mm，5μm）；流动相为水（用磷酸调节pH值为4．0）-乙腈-甲醇（50：30：20）；流速为0．8mL·min^-1；检测波长为288nm。结果：可以使水飞蓟素及其制剂中的水飞蓟宾和异水飞蓟宾达到基线分离；水飞蓟宾在0．1504—0．9024μg范围内线性良好，r〉0．9999。结论：该方法流动相组成简单，分离效果好，快速准确，并且具有较好的重复性，可用于水飞蓟素原料及制剂的检测。     

水飞蓟素羟丙基-β-环糊精包合物在大鼠体内的生物利用度

目的:研究水飞蓟素的羟丙基-β-环糊精包合物在大鼠体内的相对生物利用度。方法:给大鼠口服单剂量水飞蓟素羟丙基-β-环糊精包合物(受试样品)和水飞蓟宾胶囊剂(参比样品),用反相高效液相色谱法测定大鼠血浆中水飞蓟宾的浓度,并采用3P97程序进行统计学分析。结果:口服水飞蓟素后大鼠血浆药物浓度-时间曲线符合二室模型。受试样品中水飞蓟宾的Cm ax,tm ax,t1/2,AUC0-∞分别为(0.9±0.3)mg.L-1,(0.50±0.21)h,(12.6±3.7)h,(4.2±0.9)h.mg.L-1,参比样品中水飞蓟宾的Cm ax,tm ax,t1/2,AUC0-∞分别为(0.4±0.3)mg.L-1,(1.0±0.6)h,(31.2±15.0)h,(3.0±0.8)h.mg.L-1。受试样品中水飞蓟宾的相对生物利用度为(142.0±38.4)%。结论:与参比样品相比,受试样品的生物利用度较高。     

高效液相色谱法测定肝安胶囊中水飞蓟宾的含量

目的建立高效液相色谱法测定肝安胶囊中水飞蓟宾的含量。方法使用Agilent Zorbax SB—C18柱（4．6mm×250mm,5μm）,流动相：1％冰醋酸-甲醇=50：50,流速：1．0ml／min,柱温：30℃,检测波长：287nm,测定10批肝安胶囊中水飞蓟宾的含量。结果水飞蓟宾在10．28～123．36μg／ml（r=1）浓度范围内线性关系良好,回收率为97．00％（RSD=0．68％）。10批肝安胶囊中水飞蓟宾含量为11．11～16．65mg／粒。结论该方法简便、准确、重复性好,可以用于肝安胶囊的质量控制。     

高效液相色谱梯度洗脱法测定水飞蓟素自微乳化制剂中水飞蓟宾的含量

目的:建立一种用HPLC梯度洗脱法测定水飞蓟素自微乳化制剂中水飞蓟宾含量的方法.方法:采用Symmetry Cts色谱柱(3.9 mm×150 mm,5 μm);流动相为混合溶剂A[水-磷酸(100:0.5)]和混合溶剂B[甲醇水-磷酸(80:20:0.5)];流速:0.8 mL·min-1;检测波长:288 nm;柱温:40℃.结果:水飞蓟宾在0.293 7～0.881 μg范围内线性关系良好(r=0.999 6),方法的精密度为99.30%,加样回收率为99.88%(RSD为0.699%,n=9).结论:建立的方法准确度高,重复性好,本实验为水飞蓟素自微乳化制剂质量标准的制定提供了方法学依据.     

Flavonolignan Production in Cell Suspension Culture of Silybum marianum

The fruits of Silybum marianum (L.) Gaertn (Compositae) contain silymarin, an isomeric mixture of flavonolignans (silybin, silychristin, and silydianin). Silymarin acts as a strong anti-hepatotoxic. Silybum marianum cell cultures represent an alternate source of flavonolignans, but the yields of these compounds in such cultures are very low. In this study, in vitro cell culture systems of Silybum marianum were used to monitor the effect of elicitation (picloram, jasmonic acid, and light) on cell growth and production of silymarin. The presence of silymarin was established by high performance liquid chromatography and the greatest growth rates dry weight (32 mg) and silymarin content (0.413 mg g^{? 1} DW) were obtained with 3 mg l^{? 1} picloram and 2 mg l^{? 1} jasmonic acid in darkness after 28 days. The light grown cell suspension cultures showed reduced growth in term of dry weight (24 mg) and silymarin content. The data presented in this study demonstrate that media supplemented with 3 mg l^{? 1} picloram with JA in dark conditions can be useful for production of silymarin and growth in cell suspension cultures of Silybum marianum.     

Interaction of milk-thistle-fruit flavanonols with Langmuir monolayers of lecithin and bilayers of liposomes

Interactions of silybin and dihydroquercetin (taxifolin), flavanonols from milk thistle [Silybum marianum (L.) Gaertn.] fruits, with Langmuir monolayers of lecithin and bilayers of liposomes are compared. It is established that the investigated flavanonols have different mechanisms of action. Taxifolin produces predominantly membrane-stabilizing action whereas silybin is characterized by immobilization in the hydrophobic part of the phospholipid bilayer with the formation of more hydrophilic micellar structures. The presence of silybin and taxifolin in the liquid extract of milk thistle fruits suggests that a dual mechanism of action may occur in this preparation and also in other combined medicines based on these fruits. The results of this study show good prospects for creating combined preparations based on milk thistle fruit, taxifolin, and other flavonoids (quercetin, rutin, diosmin, etc.) possessing pronounced membrane-stabilizing action. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 43, No. 2, pp. 33–42, February, 2009.     

水飞蓟果实中的黄酮类化合物

从菊科水飞蓟属植物水飞蓟(Silybum marianum L.Gaertn)的干燥成熟果实中分离鉴定了9个化合物,分别为黄酮木质素类化合物:水飞蓟宾(1),2,3-脱氢水飞蓟宾(2),水飞蓟亭(3),2,3-脱氢水飞蓟亭(4);黄酮类化合物:4’-甲氧基紫杉叶素(5),紫杉叶素(6),二氢山奈酚(7),槲皮素(8)以及酚酸类化合物:3,4-二羟基苯甲酸(9)。其中化合物5,7,9为首次从该属植物中分得。     

Anti-phalloidine activity of the silymarins silybine and disilybine]

Originating from silybin, a phenylchromanone from Silybum marianum (L.) Gaertn., a dimer -- disilybin -- was prepared. Disilybin exhibits a phalloidin antagonistic activity at least 10 times that of silybin with regards to a dose of the same weight.     

Binding of silymarin substances to plasma proteins and synthetic polymers

Binding of Silymarin Substances to Plasma Proteins and Synthetic Polymers Silybin, silydianin, and silychristin, the main components of silymarin, the active principle of the Milk Thistle (Silybum marianum (L.) Gaertn.), are tightly but reversibly bound to human albumine and poly(vinylpyrrolidone) in vitro.     

水飞蓟煎剂治疗急性鹅膏肽类毒素致肝损伤的实验研究

目的探讨水飞蓟煎剂治疗急性鹅膏肽类毒素所致肝损伤的解毒机制。方法选用健康sD大鼠32只,随机分成4组（每组8只）：正常对照组、中毒对照组、水飞蓟煎剂1g／mL组、水飞蓟煎剂3g／mL组。除正常对照组外,其余3组均制成急性鹅膏毒蕈中毒鼠模型。造模后每日给予相应药物,3d后观察大鼠的存活情况,并采血检查谷丙转氨酶（A坍）、谷草转氨酶（AST）和用紫外分光光度法测定肝细胞RNA聚合酶活性。结果中毒对照组的血浆ALl’和AST较正常对照组明显增加（P〈0．01）,不同剂量水飞蓟煎剂灌胃治疗3d后,2组血浆ALT和AST较中毒对照组明显降低,2组问比较差异有统计学意义;中毒对照组肝细胞RNA聚合酶活性明显低于正常对照组（P〈0．01）,水飞蓟煎剂治疗组肝细胞RNA聚合酶活性明显高于正常对照组（P〈0．01）,同时治疗组之间呈量一效关系（P〈0．01）。结论水飞蓟煎剂对鹅膏毒蕈中毒肝有明显保护作用,且作用呈量一效关系,其机制可能与提高肝细胞RNA聚合酶活性有关。     

水飞蓟宾类黄酮木质素衍生物的研究进展

水飞蓟是多国药典收载的天然药物,具有抗氧化、抗纤维化、抗炎、免疫调节以及肝细胞再生作用,临床用于治疗肝炎、脂肪肝、肝硬化、缺血性损伤、辐射损伤等。近期随着水飞蓟宾以抗肿瘤新药进入Ⅱ期临床试验,对其衍生物、构效关系以及抗氧化机制等的研究进入加速阶段。本文综述了近年来水飞蓟宾和脱氢水飞蓟宾的近百种衍生物及其活性研究结果 ,并对该类黄酮木质素类化合物今后的发展和设计研究状况做一概述。     

Enhanced production of silymarin by Ag+ elicitor in cell suspension cultures of Silybum marianum

Cell suspension cultures of Silybum marianum L. Gaertn (Compositae) produce silymarin, a mixture of flavonolignans. In an attempt to increase cell growth and silymarin production, we exposed cell cultures to various levels of Ag⁺ (0.2, 0.4, 0.8, 1, and 2?mM) for different exposure times (12, 24, 48, 72, 144, and 216?h). A dramatic increase in cell growth was observed after 12?h in media supplemented with 0.2, 0.4, 0.8, and 1?mM Ag⁺, and the value in medium treated by 1?mM Ag⁺ after 72?h was 7.21?g, which was about two-fold that of the control (3.32?g). The highest silymarin production reached about 56 μg g^?1 DW, 24?h after treatment with Ag⁺ (0.8?mM), which was 30-fold that of the control. Silybin, isosilybin, silychristin, silydianin, and taxifolin were abundant flavonolignans. Ag⁺ in low concentrations is a positive elicitor for cell growth and silymarin production in cell suspension cultures of Silybum marianum.     

The effects of silymarin on experimental phalloidine poisoning.

The hepatoprotective action of silymarin, the active principle extracted from the fruit of Silybum marianum (L.) Gaertn., in animals (dogs, rabbits, rats, mice) intoxicated with phalloidine is evident, both after protective and curative treatment. A dose of 15 mg/kg of silymarin protects every animal when given 60 min before the toxin. When injected 10 mim after phalloidine, a dose of 100 mg/kg of silymarin again provides total protection. However, as the time span between administration of the toxic substance and start of treatment increases, so the efficacy of silymarin decreases; after 30 min its curative effect is negligible. The histochemical and histoenzymological studies show that during intoxication of the mice by phalloidine, silymarin inhibits the effect of the toxic substance and regulates the functions of the hepatocyte, when given either 60 min before or 10 min after phalloidine.     

中药鸦胆子总苦木内酯提取物中鸦胆苦醇的含量测定

目的建立RP HPLC法测定中药鸦胆子总苦木内酯提取物中鸦胆苦醇的含量。方法采用RP HPLC法:色谱柱为C18柱(250 mm×4.6 mm,5μm),流动相为甲醇水(体积比为41∶59),检测波长为277 nm,柱温34℃。结果鸦胆苦醇质量浓度在43.6~348.8 mg.L-1内与峰面积呈良好的线性关系,r=0.999 9(n=5),平均回收率为100.7%,RSD为1.6%(n=9)。结论测定方法准确、可靠,为鸦胆子总苦木内酯提取物质量评价提供了可靠的依据。