CN106333945A - 青蒿素或青蒿素衍生物在制备治疗良性前列腺增生和脱发药物中的应用 - Google Patents
青蒿素或青蒿素衍生物在制备治疗良性前列腺增生和脱发药物中的应用 Download PDFInfo
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- artemisinin
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Abstract
本发明公开了青蒿素或青蒿素衍生物在制备治疗良性前列腺增生和脱发药物中的应用,所述青蒿素衍生物包括二氢青蒿素、蒿甲醚、蒿乙醚或青蒿琥酯。进一步地,将青蒿素或青蒿素衍生物溶于有机溶剂中,加入聚乙烯吡咯烷酮,加热溶解,干燥后得到固体分散体。将上述青蒿素及其衍生物制备成固体分散体,可以克服原料药青蒿素及青蒿素类衍生物(二氢青蒿素、蒿甲醚、蒿乙醚、青蒿琥酯)水溶性差的难点,对良性前列腺增生及脱发具有很好的治疗效果。在制备治疗良性前列腺增生及脱发等方面具有潜在的临床应用价值。
Description
技术领域
本发明属于药物应用技术领域,更具体地,涉及青蒿素或青蒿素衍生物在制备治疗良性前列腺增生和脱发药物中的应用。
背景技术
良性前列腺增生症(Benign Prostatic Hyperplasia, BPH)是前列腺尿道周围细胞增生,腺体进行性肿大,使前列腺尿道狭窄,引起膀胱尿液流出梗塞。临床表现为尿频、排尿困难、尿潴留等下尿路症状(LUTS)症状。这是一种常见的男性老年性疾病。50岁以上的男性大约30%~50%的人会出现不同程度的良性前列腺增生, 且发病率随着年龄增大而增加。据报道,70岁~79岁的男性发病率为70%,80岁以上的男性则高达90%。现有治疗该疾病的药物以非那甾胺(Finasteride,商品名:保列治、保发治)为代表,作用机理是抑制5a-还原酶的活性,抑制前列腺增生以及治疗脱发,存在造成患者阳痿、少精等副作用。因此,研究开发一种治疗良性前列腺增生、脱发疾病药物,而且效果好、毒副作用小,这对保证老年人健康将具有十分重要的意义。
青蒿( Artemisia annua L.) 为菊科蒿属一年生草本植物,是我国传统中药,具清热解暑的功效。青蒿素( Artemisinin) 是我国科研人员从青蒿叶中提取分离得到的倍半萜内酯化合物,其衍生物主要有双氢青蒿素( dihydroartemisinin) 、青蒿琥酯(artesunate) 、蒿甲醚( artemather) 和蒿乙醚( arteether) 等,多年的临床研究证明青蒿素及青蒿素类衍生物具有很好的抗疟疾作用,在治疗艾滋病和肿瘤等疾病方面具有潜在的临床应用价值。公开的专利文件CN201210380878.3介绍青蒿素及青蒿琥酯在抗阿尔茨海默病的医疗用途。专利文件CN201010506509.5公开一种含有青蒿素及青蒿素类衍生物与Bcl-2抑制剂的药物组合物及其在制备治疗结肠癌、肝癌、肺癌、肾癌、胃癌、脑瘤、肉瘤、胰腺癌、卵巢癌、乳腺癌或前列腺癌的药物中的应用。专利文件CN200710078254.5公开了一种现有的抗疟药青蒿素及其衍生物二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯的新用途,即与抗菌药物联合应用抑制细菌生长,增强抗菌药物抗菌效力。本专利申请青蒿素及其衍生物二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯为原料,在治疗前列腺增生以及脱发的医药新用途。
目前,临床上应用的青蒿素类药物制剂普遍存在溶解度差、首过效应高、生物利用度低、给药频繁、疟原虫复燃率高等缺点,本专利解决青蒿素类药物溶解性差的难点。
发明内容
本发明的目的在于根据现有技术中的不足,提供了青蒿素或青蒿素衍生物在制备治疗良性前列腺增生和脱发药物中的应用。
本发明的目的通过以下技术方案实现:
本发明提供了青蒿素或青蒿素衍生物在制备治疗良性前列腺增生和脱发药物中的应用,所述青蒿素衍生物包括二氢青蒿素、蒿甲醚、 蒿乙醚或青蒿琥酯。
优选地,将青蒿素或青蒿素衍生物溶于有机溶剂中,加入聚乙烯吡咯烷酮,加热溶解,干燥后得到固体分散体。
优选地,所述青蒿素或青蒿素衍生物与聚乙烯吡咯烷酮的质量比为1:0.5~1:400。
优选地,所述青蒿素或青蒿素衍生物与聚乙烯吡咯烷酮的质量比为1:1~1:80。
最优选地,所述青蒿素或青蒿素衍生物与聚乙烯吡咯烷酮的质量比为1:10。
优选地,所述干燥为喷雾干燥,喷雾干燥的温度为70~80℃。
优选地,当应用于制备脱发药物时,使用有机溶剂将固体分散体配置成20mg/100ml的溶液,早晚各喷涂1次。
优选地,所述有机溶剂为无水乙醇。
优选地,当应用于制备治疗良性前列腺增生药物时,按照200~600mg/Kg体重的剂量使用固体分散体。
本发明同时保护上述青蒿素或青蒿素衍生物在制备治疗良性前列腺增生、脱发的药物、保健食品、健康护理品中的应用。
与现有技术相比,本发明具有以下优点及有益效果:
将上述青蒿素及其衍生物制备成固体分散体,可以克服原料药青蒿素及青蒿素类衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯)水溶性差的难点,对良性前列腺增生及脱发具有很好的治疗效果。在制备治疗良性前列腺增生及脱发等方面具有潜在的临床应用价值。
具体实施方式
下面通过实施例对本发明来做进一步详细说明,这些实施例仅用来说明本发明,并不限制本发明的范围。
实施例1 青蒿素及其衍生物固体分散体制备
分别取青蒿素或青蒿素衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯 )各6克,分别溶于400毫升无水乙醇中,加入聚乙烯吡咯烷酮(PVP K30) 60克,加热溶解,使用小型喷雾干燥机75℃喷雾干燥,分别得到青蒿素或其衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯 )固体分散体约63克。
采用紫外分光光度法测定固体分散体中青蒿素含量。取500毫克青蒿素或其衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯 )固体分散体(青蒿素或其衍生物:PVP K30=1:10)溶于蒸馏水20毫升,采用0.22微米的滤膜过滤,在292nm 波长处测定紫外吸光度, 与同样质量(50毫克)的青蒿素或其衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯 )在292nm波长处的吸光度比值,获得比值分别为8.9、9.0、8.8、8.6、8.9,这反映制备固体分散体方法大大提高青蒿素或其衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯 )原料药的溶解性。
实施例2 青蒿素及其衍生物固体分散体在制备治疗良性前列腺增生中的应用
一.材料
1.1 实验动物:健康昆明小鼠,4周龄,雄性,80只,体重约20克;10天龄胎鼠,40只,均由广东省医学实验动物中心提供。
1.2 实验药品及试剂:阳性对照药:保列治,默沙东(英国)公司,美国默克公司分部,分装厂家,杭州默沙东制药有限公司;青蒿素及其衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯 )固体分散体(制备方法如实施例1);酸性磷酸酶(ACP)测试盒,由南京建成生物工程研究所提供;由南京建成生物工程研究所。
二.方法与结果
选取80只健康雄性昆明小鼠饲养一周后,腹腔注射水合氯醛麻醉后,无菌操作剖开腹部, 仔细分离前列腺腹叶, 在手术显微镜下用显微镊子向两个前列腺腹叶内各植入1 个16天龄胎鼠的尿生殖窦组织, 逐层缝合腹壁。假手术对照组仅用镊子尖端刺入前列腺组织。分为8个组,分别为假手术对照组、模型组、青蒿素固体分散体组、二氢青蒿素固体分散体组、蒿甲醚固体分散体组、 蒿乙醚固体分散体组、青蒿琥酯固体分散体组、阳性药物组,每组10只。同时开始给予受试物,每天通过灌胃方式给药,假手术对照组、模型组大鼠灌胃给予PVP 240mg/Kg体重, 青蒿素固体分散体组、二氢青蒿素固体分散体组、蒿甲醚固体分散体组、 蒿乙醚固体分散体组、青蒿琥酯固体分散体组小鼠灌胃剂量分别对应给予青蒿素、二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯 240mg/Kg体重, 阳性药物组给予保列治1mg/Kg体重, 持续灌胃40天。连续给药40天,第41天称量体重,摘眼取血,离心分离血清,称取前列腺(腹叶+背叶),计算前列腺脏器指数=前列腺(腹叶+背叶)/体重),测定ACP活性。T检验统计分析,结果如表1所示。
表1 青蒿素及其衍生物固体分散体对氯化镉诱导小鼠良性前列腺增生模型的影响(±S.D., n=10)
由实验结果可知,尿生殖窦诱导小鼠良性前列腺增生模型中,模型对照组的前列腺(腹叶+腹叶)指数均比正常对照组有明显增加(P<0.001),提示良性前列腺增生模型制备成功。口服灌胃给予青蒿素及其衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯)固体分散体分别对小鼠前列腺(腹叶+腹叶)指数均有明显的降低作用(P<0.05),同时降低血清ACP活性(P<0.001),说明青蒿素及其衍生物(二氢青蒿素、蒿甲醚、 蒿乙醚、青蒿琥酯)具有治疗良性前列腺增生的药理作用。
实施例3 青蒿素及其衍生物治疗脱发的作用
一.材料
1.1 青蒿素及其衍生物固体分散体(制备同实施例1;使用时用无水乙醇配成含有青蒿素及其衍生物20mg/100ml浓度,每次喷涂脱发处均湿润为适量,每天早午晚各喷涂1 次。
二.方法与结果
选取全头性圆形脱发患者80 例,其中男性53例,女性47例,年龄40岁至65 岁,试用90天,生发出硬发者48例,生发出硬发浓密者32例,试用180 天,生发生出硬发者63例,生发出硬发浓密者55例,总有效率93%,显效率78%,无效率7%,表明青蒿素及其衍生物固体分散体具有治疗脱发的作用。
Claims (10)
1.青蒿素或青蒿素衍生物在制备治疗良性前列腺增生和脱发药物中的应用,其特征在于,所述青蒿素衍生物包括二氢青蒿素、蒿甲醚、 蒿乙醚或青蒿琥酯。
2.根据权利要求1所述的应用,其特征在于,将青蒿素或青蒿素衍生物溶于有机溶剂中,加入聚乙烯吡咯烷酮,加热溶解,干燥后得到固体分散体。
3.根据权利要求2所述的应用,其特征在于,所述青蒿素或青蒿素衍生物与聚乙烯吡咯烷酮的质量比为1:0.5~1:400。
4.根据权利要求2所述的应用,其特征在于,所述青蒿素或青蒿素衍生物与聚乙烯吡咯烷酮的质量比为1:1~1:80。
5.根据权利要求2所述的应用,其特征在于,所述青蒿素或青蒿素衍生物与聚乙烯吡咯烷酮的质量比为1:10。
6.根据权利要求2所述的应用,其特征在于,所述干燥为喷雾干燥,喷雾干燥的温度为70~80℃。
7.根据权利要求2所述的应用,其特征在于,当应用于制备脱发药物时,使用有机溶剂将固体分散体配置成20mg/100ml的溶液,早晚各喷涂1次。
8.根据权利要求7所述的应用,其特征在于,所述有机溶剂为无水乙醇。
9.根据权利要求2所述的应用,其特征在于,当应用于制备治疗良性前列腺增生药物时,按照200~600mg/Kg体重的剂量使用固体分散体。
10.青蒿素或青蒿素衍生物在制备脱发护理品中的应用,其特征在于,所述青蒿素衍生物包括二氢青蒿素、蒿甲醚、 蒿乙醚或青蒿琥酯。
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