口服青蒿琥酯对伯氏鼠疟和诺氏猴疟的杀灭效果

目的:研究青蒿琥酯口服对伯氏鼠疟和诺氏猴疟的血液裂殖体杀灭效果。方法:分别在鼠疟和猴疟模型上采用“4-day试验法”、“28-day试验法”和“7-day试验法”检测了青蒿琥酯和氯喹的药效。结果:口服青蒿琥酯对伯氏鼠疟民K_(173)株的抑制效果低于氯喹,但其原虫血症下降50％、90％和转阴的时间比氯喹快10-15h,对抗株RC/K_(173)的疗效优于氯喹,无交叉抗性,I_(90)仅为1.4。青蒿琥酯和氯喹对诺氏猴疟在31.6,10.0和3.16mg·kg~(-1)剂量组的试验猴全部治愈。结论:口服青蒿琥酯在鼠、猴疟模型上的药效研究为临床研究提供有益参考。     

青蒿研究的现状

本品为菊科植物黄花蒿(Artomisia annul L)的干燥地上部分。味苦,辛性寒,有清热解暑,除虱,截疟的功能。主治暑邪发热,阴虚发热,夜热早凉,骨蒸劳热,疟疾寒热和湿热黄疸。中药青蒿载于马王堆出土《五十二病方》,《神农本草经》。晋葛洪《时后备急方》治疟病方载有:“青蒿一握,以水二升渍,绞取汁尽服之。”此后,宋,元,明各作家医籍本草均有以复方“青蒿汤”,“截疟青蒿丸”,“青蒿散”制疟。李时珍亦称青蒿“制疟疾寒热”清代《瘟病条辨》用“青蒿鳖甲煎”“治少阳疟”。民间亦有流传使用。我国南省北诸省如广西,广     

口服青蒿琥酯对伯氏鼠疟和诺氏猴疟的杀灭效果

目的：研究青芒琥酯口服对伯氏鼠疟和诺氏猴疟的血液开明植体杀灭效果。方法：分别在鼠疟和猴疟模型上采用“４－ｄａｙ试验法”、“２８ｄａｙ”和“７－ｄａｙ”试验法检测了青蒿琥酯和氯喹的药效。结果：口服青蒿琥酯对伯氏鼠疟Ｋ１７３株的抑制效果低于氯喹,但其原虫血症下降５０％、９０％和有的时间比氯喹快１０－１５ｈ,对抗株ＲＣ／Ｋ１７３的疗效优于氯喹,无交叉抗性,Ｉ９０仅为１．４。青蒿琥酯和氯喹对诺氏猴疟在３１     

青蒿琥酯经皮肤吸收治疗猴疟的疗效

青蒿琥酯为高效、速效、低毒的抗疟新药,但近期复燃率较高。为了提高疗效,方便使用,乃研究其经皮肤吸收制剂。青蒿琥酯经皮肤吸收对鼠疟的疗效,在小鼠及兔体内的药代动力学研究已取得较好的结果,现报告对猴疟的疗效。     

青蒿琥酯

青蒿琥酯为一种对恶性疟有快速治疗效果的抗疟药，既能口服，又可经直肠和胃肠外给药，因此，成为治疗严重疟疾，包括脑型疟的理想药物。至今没有明显的计算所说明青蒿琥酯治疗的脑型疟病人的的死亡率比标准奎宁疗法要高。     

青蒿琥酯对小鼠免疫功能的影响

研究青蒿琥酯对小鼠免疫功能的影响，溶血素含量用分光光度法测定，血清ＩｇＧ和Ｃ３含量用单向免疫扩散法测定，淋巴细胞转化率、巨噬细胞吞噬百分率和吞噬指数镜检计数。青蒿琥酯ｉｍ７５ｍｇｋｇ＾－１ｂｉｄｆｏｒ５－７ｄ能降低ＳＲＢＣ致敏小鼠血清溶血素和ＩｇＧ的含量，抑制抗体生成，但增加疟鼠补体Ｃ３的含量。     

不同产地的青蒿药用成分含量研究

目的：研究不同产地的青蒿药用成分的含量。方法：从全国各地采集22批青蒿药材,通过高效液相色谱法测定药材中的青蒿酸、青蒿乙素、青蒿素和东莨菪内酯的含量,并以所测含量为指标,进行相关分析和聚类分析。结果：相关分析和聚类分析均显示,不同产地的青蒿中上述4种成分含量差异较大,各自聚为一类。结论：青蒿活性成分的积累与产地有一定的相关性。     

青蒿琥酯对小鼠免疫功能的影响(英文)

目的:研究青蒿琥酯对小鼠免疫功能的影响. 方法:溶血素含量用分光光度法测定,血清IgG和C3含量用单向免疫扩散法测定,淋巴细胞转化率、巨噬细胞吞噬百分率和吞噬指数镜检计数.结果:青蒿琥酯im 75 mg kg~(-1) bidfor 5—7d能降低SRBC致敏小鼠血清溶血素和IgG的含量,抑制抗体生成,但增加疟鼠补体C3的含量.青蒿琥酯能促进PHA诱导的小鼠体内淋巴细胞转化,能提高DNFB所致的迟发型超敏反应,并减少腹腔巨噬细胞的吞噬百分率和吞噬指数.结论:青蒿琥酯对体液免疫有抑制作用,但对细胞免疫有促进作用.     

HPLC-UV-ELSD法同时测定青蒿中青蒿素、青蒿乙素和青蒿酸的含量

用HPLC-UV-ELSD法同时测定青蒿药材中青蒿素、青蒿乙素和青蒿酸的含量。采用Nucleodur C₁₈色谱柱(250 mm×4.6 mm，5 μm ID)；以乙腈-0.1%乙酸水(50∶50)为流动相；紫外检测波长209 nm,蒸发光散射检测器漂移管温度50 ℃。结果显示，青蒿素、青蒿乙素和青蒿酸能够达到很好分离。它们的线性范围分别为0.52～2.6 μg， r=0.999 4(n=5)； 0.022～4.4 μg， r=0.999 9(n=5)； 0.203～8.12 μg，r=0.999 8(n=5)。平均回收率分别为99.45%(RSD=2.3%， n=6)；102.37%(RSD=1.7%， n=6)；101.10%(RSD=0.79%， n=6)。本法简单、准确、快速，可同时测定青蒿药材中青蒿素、青蒿乙素和青蒿酸的含量。     

青蒿琥酯对前列腺癌PC-3细胞的抑制作用

目的:观察青蒿琥酯对前列腺癌细胞株PC-3的体外作用,并探讨其可能作用机制。方法:应用光镜形态学、MTT法、流式细胞仪观察不同浓度青蒿琥酯在体外对前列腺癌细胞系PC-3的作用和对细胞DNA含量的影响。结果:青蒿琥酯对前列腺癌细胞系PC-3有明显的生长抑制作用,并能诱导细胞凋亡和抑制细胞增殖周期。结论:青蒿琥酯对前列腺癌PC-3细胞有明显生长抑制和凋亡诱导作用,提示青蒿琥酯有用于治疗激素非依赖性前列腺癌的可能性。     

静脉注射青蒿酯后人体尿药排泄数据的初步分析

在抢救危重疟疾、特别是脑型疟疾时,青蒿酯是目前唯一能静脉注射给药以迅速控制原虫发育并获得较高疗效的药物。前文报告了应用还原型电化学检测高效液相色谱法测定人体静脉注射青蒿酯后的血药数据。本文则对尿药数据进行了初步总结并和相应的血药数据进行了比较。     

青蒿素类似物的研究 Ⅳ.含卤素、氮、硫等杂原子的青蒿素衍生物的合成

为增强双氢青蒿素酯和醚类衍生物的抗疟作用,我们合成了42个侧链上带有卤素、氮或硫取代的双氢青蒿素酯和醚类化合物。抗疟筛选表明,多数化合物的活性高于青蒿素,但并未超过相应的无杂原子取代的衍生物,唯双氢青蒿素的问-三氟甲基苯甲酸酯(17)的抗疟活性为间-甲基苯甲酸酯的4倍,化合物(17)和(6)为青蒿素的10倍。     

青蒿素类似物的研究 Ⅲ.二氢青蒿素二元酸双酯和单酯类衍生物的合成

青蒿素是新型化学结构的抗疟药。为了克服复燃率高及不溶解于水的缺点,我们以二氢青蒿素为原料与二元酸或酸酐和二环已基碳二亚胺(DCC)在4-二甲氨基吡啶(DMAP)催化下合成一系列的二氢青蒿素二元酸双酯及单酯类衍生物。经鼠疟(Plasmodium berghei)抗氯喹虫株筛选结果表明,化合物3的抗疟效果比青蒿素强9倍。     

青蒿素类似物的研究 Ⅲ.二氢青蒿素二元酸双酯和单酯类衍生物的合成

青蒿素是新型化学结构的抗疟药。为了克服复燃率高及不溶解于水的缺点,我们以二氢青蒿素为原料与二元酸或酸酐和二环已基碳二亚胺(DCC)在4-二甲氨基吡啶(DMAP)催化下合成一系列的二氢青蒿素二元酸双酯及单酯类衍生物。经鼠疟(Plasmodium berghei)抗氯喹虫株筛选结果表明,化合物3的抗疟效果比青蒿素强9倍。     

双氢青蒿素在人的药代动力学及与青蒿素的比较

用放射免疫测定法研究青蒿素和双氢青蒿素在人的药代动力学结果:人口服青蒿素片剂15 mg/kg后1.5 h,血药峰值达0.09μg/ml,MRT为3.27 h,而口服双氢青蒿素仅1.1 mg/kg和2.2mg/kg后1.33 h,血药峰浓度分别为0.13μg/ml和0.71μg/ml,MRT分别为2.36和2.26 h,可见,青蒿素片剂的生物利用度仅为双氢青蒿素的1.62%～10.08%,所以口服宜用双氢青蒿素。直肠给青蒿素栓剂15 mg/kg和双氢青蒿素栓剂8 mg/kg后,血药分别于4.6 h和4.7 h达峰浓度0.04 μg/ml和0.11 μg/ml,MRT分别为6.98 h和6.96 h,可见青蒿素栓剂的生物利用度仅为双氢青蒿素者的29%,作为栓剂也可用双氢青蒿素。     

A comparison of oral artesunate and artemether antimalarial bioactivities in acute falciparum malaria

AIMS: Artesunate and artemether are the two most widely used artemisinin derivatives in the treatment of uncomplicated Plasmodium falciparum malaria, but there is little information on their comparative pharmacokinetics. The aim of this study was to examine the relative oral antimalarial bioavailability and pharmacokinetics of the two derivatives. METHODS: The pharmacokinetic properties of oral artesunate and artemether (4 mg kg(-1)) were compared in a randomized cross-over study of 14 adult patients in western Thailand with acute uncomplicated Plasmodium falciparum malaria. Antimalarial activity was compared using a previously validated, sensitive bioassay. RESULTS: Despite a 29% lower molar dose, oral artesunate administration resulted in significantly larger mean area under the plasma antimalarial activity time curve and median maximum plasma antimalarial activity than after oral artemether (P 相似文献   

Orally active antimalarials: hydrolytically stable derivatives of 10-trifluoromethyl anhydrodihydroartemisinin

New fluoroartemisinin derivatives containing polar or water-soluble functionalities at C-16 (11a-j, 12a-g) were synthesized using the key intermediate 16-bromo-10-trifluoromethyl anhydrodihydroartemisinin 10. The substitution reaction from 10 was more selective than that from the nonfluorinated parent bromide; the allylic bromide 10 underwent no allylic rearrangement and provided only nucleophilic substitution products in high yields with N-, O-, and C-nucleophiles. Among them, amines 11a-c appeared to be highly in vivo efficient antimalarials on mice infected with Plasmodium berghei, more than the reference sodium artesunate 1d. In particular, the most effective piperazinoethanol derivative 11b cured all mice after oral treatment at a dose lower than 10 mg/kg. Further pharmacokinetic studies showed that the bioavailability in rats following oral administration was 25 times greater for 11b than for artemether 1b.     

Artemisinin drugs: novel antimalarial agents

Artemisinin and its derivatives, artesunate and artemether, represent a new class of antimicrobial drug with potent activity against Plasmodium falciparum. Although they show excellent efficacy in both severe and uncomplicated malaria, dosage regimens still need to be optimised and pharmacokinetic profiles defined. In the treatment of uncomplicated malaria, the artemisinin drugs should be used in combination with a long acting antimalarial to protect both drugs against the emergence of resistance. In the treatment of severe malaria, parenteral artemether is at least as effective as quinine and is simpler to use. The use of rectal preparations of artesunate and artemisinin at the rural health level will facilitate early initiation of the treatment of falciparum malaria and this may reduce the proportion of patients progressing to severe disease. All of the artemisinin drugs have comparable efficacy; the choice of derivative should be based upon availability, cost and quality of the preparation. Artemisinin, artesunate and artemether are well-tolerated in both adults and children, with no evidence to date of serious clinical toxicity.     

Artemisinin drugs: novel antimalarial agents

Artemisinin and its derivatives, artesunate and artemether, represent a new class of antimicrobial drug with potent activity against Plasmodium falciparum. Although they show excellent efficacy in both severe and uncomplicated malaria, dosage regimens still need to be optimised and pharmacokinetic profiles defined. In the treatment of uncomplicated malaria, the artemisinin drugs should be used in combination with a long acting antimalarial to protect both drugs against the emergence of resistance. In the treatment of severe malaria, parenteral artemether is at least as effective as quinine and is simpler to use. The use of rectal preparations of artesunate and artemisinin at the rural health level will facilitate early initiation of the treatment of falciparum malaria and this may reduce the proportion of patients progressing to severe disease. All of the artemisinin drugs have comparable efficacy; the choice of derivative should be based upon availability, cost and quality of the preparation. Artemisinin, artesunate and artemether are well-tolerated in both adults and children, with no evidence to date of serious clinical toxicity.     

青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究

将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5～4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。