CN115137774A - 胆木叶提取物在制备抗克柔念珠菌药物中的应用 - Google Patents
胆木叶提取物在制备抗克柔念珠菌药物中的应用 Download PDFInfo
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Abstract
本发明公开了一种胆木叶提取物在制备抗克柔念珠菌药物中的应用。胆木叶提取物的制备方法为：精密称取胆木叶适量，乙醇回流提取，提取液浓缩，蒸干，得到胆木叶提取物。胆木叶提取物的最低抑菌浓度MIC为47.2µg/mL。抗克柔念珠菌药物选自口服给药剂型或外用给药剂型。口服给药剂型选自汤剂、颗粒剂、胶囊剂、片剂、口服液、丸剂、酊剂、糖浆剂。外用给药剂型选自凝胶剂、喷雾剂、软膏剂、贴剂、巴布剂、洗剂、乳膏剂、栓剂。本发明研究发现，胆木叶提取物对克柔念珠菌有很好抑制作用、同时不会产生耐药性，适合作为新一代的抑克柔念珠菌的有效药物，本发明可以对胆木叶提取物的研究开发提供一定的研究基础和思路。
Description
技术领域
本发明涉及一种胆木叶提取物在制备抗克柔念珠菌药物中的应用，属于提 取物技术领域。
背景技术
念珠菌属物种是全身和局部机会性感染的病原微生物，并且是全球医院血 流感染的第四个主要原因[1]。克柔念珠菌引起的感染通常在免疫功能低下的患 者中，尤其是患有人免疫缺陷病毒(HIV)获得性免疫缺陷综合征和血液恶性 肿瘤的患者。据报道，克柔念珠菌血症患者的死亡率己高达60％-80％[2]。除 此之外，使用免疫抑制药不可避免地增加了克柔念珠菌感染的风险，并且克柔 念珠菌在所有念珠菌属中均排名第五[3]。由于克柔念珠菌其对氟康唑(FLC) 的具有天然抗药性以及其对氟胞嘧啶和两性霉素B(AMB)的易感性的显着降 低[4]，己被认为是多重耐药(MDR)真菌病原体。因此有必要研究开发对克柔念珠菌有很好抑制作用的药物。
[1]Chan S,Baley hospitalised children ED,Hossain J.Candida speciesbloodstream infections in A 10-year experience[J].Journal of paediatrics andchild health,2015,51(9):857-60；quiz 861.
[2]Abbas J,Bodey GP,Hanna HA,et a1.Candida krusei fungemia.Anescalating serious infection in immunocompromised patients[J].Arch Intern Med2000；160:2659-2664.
[3]Pfaller MA,Diekema DJ,Gibbs DL,et a1.Candida krusei,a multidrug-resistant opportunistic fungal pathogen:geographic and temporal trends fromthe ARTEMIS DISK Antifungal Surveillance Program,2001to 2005[J].J ClinMicrobiol 2008；46:515-521.
[4]Yadav JS,Bezawada J,Yan S,et a1.Candida krusei:biotechnologicalpotentials and concerns about its safety[J].Can J Microbiol 2012；58:937.
克柔念珠菌是一种致病性和毒力均低的一种共生菌，主要存在于热血动物 体内与免疫力低下的患者中。克柔念珠菌在显色培养基中的颜色为粉红色，在 沙保葡萄糖琼脂上生长的菌落有着暗淡、不光滑的扁平表面，而其他念珠菌菌 种则均表现为凸起的菌落。体外发现克柔念珠菌的黏附力远小于白念珠菌，但 相比其他的念珠菌有更强大细胞表面疏水性，因此克柔念珠菌有着强大的寄居 无生命物质表面如植入物和导管的能力，寄居在薄膜或生物膜的表面迅速繁 殖，这是引起相关侵袭性操作感染的主要原因。念珠菌生物膜的形成特别是异 物如导管，不仅作为传播念珠菌感染的主要来源，而且还可以使一线抗真菌剂 产生抗性，造成治疗失败，危及患者生命。另一方面由于生物膜的产生，使得 必须开发抑制生物膜的药物，造成医疗成本的增加，造成患者经济负担。念珠 菌有几种毒力因子。其中包括：黏附至宿主表面的黏附力，产生的磷脂酶、蛋 白水解酶和菌丝(帮助其逃避宿主免疫系统的防御)。诸多研究数据表明，对 氟康唑天然耐药的克柔念珠菌耐药率最高，已经成为临床上最为难治的念珠 菌。
在国内，因标本来源、时间、地区及气候的不同，各个医院的克柔念珠菌 的分离率从1.4％-8.86％不等，对氟康唑、伊曲康唑的耐药率从27.78％-100％ 不等，对唑类药物耐药现象严重。在另一项美国研究显示，克柔念珠菌对棘白 菌素类药物耐药率在2008年仅为4.2％，至2014年，其耐药率已升为7.8％。
对唑类药物的耐药机制：羊毛甾醇14α-去甲基化酶(14α-demythylase， 14-DM)是唑类药物耐药机制中的作用靶酶，该酶是由ERG11基因编码产生 的，编码蛋白ERG11p，在麦角甾醇生物的合成过程中处于关键位置，是真菌 细胞膜的主要甾醇成分，经由和14-DM结合，唑类药物抑制了其生物活性， 导致甾醇中间产物的堆积，阻碍麦角固醇的合成，最终使念珠球菌的胞膜结构 及功能发生改变，最终产生抗药性。
克柔念珠菌对唑类药物的耐药机制可能由以下几种引起。1.药物靶酶 ERG11编码基因的突变和过度表达。2.靶位拷贝数的增多。3.通过药物外排转 运蛋白和减少摄取，而降低细胞内药物浓度。4.其他的麦角固醇的生物合成途 径成分的修饰。5.生物膜和持留细胞。抑克柔念珠菌的化合物：嗜铬粒蛋白A (CGA)-N46、银纳米颗粒(Ag NP)、羧甲基壳聚糖(CM-壳聚糖)、艾沙 康唑、阿巴康唑、福司氟康唑。但是这些药物均为化学药物或者合成药物，现 有技术中未见抗克柔念珠菌的中药。
发明内容
本发明的目的是为了提供一种胆木叶提取物在制备抗克柔念珠菌药物中 的应用。
为解决上述技术问题，本发明采用的技术方案为：
胆木叶提取物在制备抗克柔念珠菌药物中的应用。
胆木叶提取物的制备方法为：精密称取胆木叶适量，乙醇回流提取，提取 液浓缩，蒸干，得到胆木叶提取物。
优选地，胆木叶提取物的制备方法为：精密称取胆木叶0.5g，65％乙醇 50mL，70℃回流提取40min，提取液旋蒸仪浓缩，蒸干，得到胆木叶提取物。
所述胆木叶提取物的最低抑菌浓度MIC为47.2μg/mL。
所述抗克柔念珠菌药物选自口服给药剂型或外用给药剂型。
所述口服给药剂型选自汤剂、颗粒剂、胶囊剂、片剂、口服液、丸剂、酊 剂、糖浆剂。
所述外用给药剂型选自凝胶剂、喷雾剂、软膏剂、贴剂、巴布剂、洗剂、 乳膏剂、栓剂。
本发明具有以下有益效果：本发明研究开发对克柔念珠菌有很好抑制作 用、同时不会产生耐药性的胆木叶提取物。
胆木，中药名。为茜草科植物乌檀Nauclea officinalis Pierre.ex Pitard的枝、干、树皮。分布于广东、广西。具有清热解毒，消肿止痛之功效。常用于感冒 发热，支气管炎，肺炎，急性扁桃体炎，咽喉炎，乳腺炎，胆囊炎，肠炎，菌 痢，尿路感染，下肢溃疡，脚癣感染，烧伤感染，疖肿，湿疹。
由此可见，胆木可以治疗多种炎症且疗效显著。现有技术中未见胆木可以 抗克柔念珠菌的报道。
乌檀有大量的叶子，俗称胆木叶，文献报道胆木叶像胆木一样，含有丰富 的生物碱，胆木叶提取部位群ELN(主要指标性成分异长春花苷内酰胺的质量 分数16％左右)具有显著的镇痛和抗炎作用。故现有技术认为，胆木叶药用部 位具有替代胆木的潜质，同时，胆木叶的采集不会破快乌檀树木的生长，对环 境更加有利，故研究人员专注于胆木叶如何取代胆木的研究，并未对胆木叶特 有的、专属性的功效(抑制克柔念珠菌)进行研究开发，而本发明研究发现， 胆木叶提取物对克柔念珠菌有很好抑制作用、同时不会产生耐药性，适合作为 新一代的抑克柔念珠菌的有效药物，本发明可以对胆木叶提取物的研究开发提 供一定的研究基础和思路。
附图说明
图1为本发明中胆木提取物对克柔念珠菌的抑菌图；
图2为胆木浸膏胶囊对克柔念珠菌的抑菌图。
具体实施方式
下面结合附图对本发明作更进一步的说明。
实验部分：
1.培养基的制备：
MH琼脂培养基的制备：称取MH琼脂培养基粉末19.0g于锅中，加入纯 化水500mL，搅拌加热至沸腾，粉末完全溶解，置于锥形瓶中，用锡箔纸封好， 放入高压蒸汽灭菌锅里面进行121.0℃、20min灭菌，同时超净工作台紫外灭 菌20min，灭菌后等培养基冷却至30℃，每个培养基的体积约为25mL。
沙氏葡萄糖琼脂培养基的制备：称取沙氏葡萄糖琼脂培养基粉末32.6g于 锅中，加入纯化水500mL，搅拌加热至沸腾，粉末完全溶解，倒入锥形瓶中， 用锡箔纸封好，再放入高压蒸汽灭菌锅里面进行121.0℃、20min灭菌，同时 超净工作台紫外灭菌20min，灭菌后等培养基冷却至30℃，每个培养基的体积 约为25mL。
2.受试菌的接种：
超净工作台需要紫外灭菌20min，点燃酒精灯让周围形成无菌环境，取接 种环在酒精灯的外焰进行灼烧，使接种环铁环烧红，冷却5秒，蘸取菌液后， 在沙氏葡萄糖琼脂培养基上采用四区划法，划完后外焰灼烧灭菌，培养基置于 32～37℃培养箱恒温培养24h。
受试菌为克柔念珠菌，又名克柔假丝酵母菌(Ck)，拉丁名Candida kruseic。
3.溶液的配制：
(1)阳性对照
精密称取氟康唑(纯度>99％)256mg于100mL棕色容量瓶内，加入纯化 水(UP＝18.2)100mL，放入超声波清洗机中振荡溶解，得到2.56mg/mL氟康 唑溶液。
(2)样品溶液的配制
精密称取胆木叶0.5g，65％乙醇，50mL，70℃回流提取40min，提取液 旋蒸仪浓缩，蒸干，得到胆木叶提取物粉末，精密称取0.3g胆木叶提取物粉末 于EP管中，加1mL纯化水溶解，得到0.3g/mL的胆木叶提取物溶液。
(3)胆木浸膏胶囊溶液的配制
取胆木浸膏胶囊一粒(海南森祺制药有限公司)，将内容物置于EP管中， 加1mL纯化水溶解，得到0.36g/mL的胆木浸膏胶囊溶液。
4.抑菌实验：
滤纸片的直径为6mm，厚度为6层，实验前先把样品溶液、氟康唑溶液、 移液枪的枪头、滤纸片、生理盐水、镊子、废物缸和麦氏比浊管进行高压蒸汽 灭菌并烘干，超净工作台紫外灭菌20min，点燃酒精灯让周围形成无菌环境， 用马克笔在培养基底部做好标记。
在无菌的环境下，加5mL生理盐水在麦氏比浊管中，挑取适量受试菌加 入其中，用涡旋机振动均匀后，用0.5号和1号的比浊管，进行比对，菌悬液 的浑浊度要在0.5号和1号比浊管的浑浊度范围内，具体见下表1。
表1比浊管的参考区间
吸取500μL真菌的受试菌菌悬液于MH琼脂培养基中，用一次性涂布棒 进行涂布，用枪头吸取多余液体并晾干，镊子经酒精灯外焰后夹取滤纸片放至 培养基上，依次加10μL氟康唑、10μL胆木叶提取物溶液和10μL胆木浸膏胶 囊溶液，加完后用封口膜封好，并放进32～37℃培养箱恒温培养24h，把用过 的麦氏比浊管和废物缸进行高压蒸汽灭菌，最后观察数据并记录。
5.胆木叶提取物和胆木浸膏胶囊对Ck菌的抑菌情况：
胆木叶提取物溶液的颜色为褐色，胆木叶提取物的抑菌圈为12mm，有 明显的抑菌圈，抑菌作用为高度敏感。克柔念珠菌对氟康唑具有天然耐药性， 可看到阳性对照物氟康唑抑菌圈内克柔念珠菌的生长，结果见表2及图1。
表2样品溶液对念珠菌的抑菌活性(抑菌圈直径：mm)
| 样品 | 阳性对照 | 胆木叶提取物 | 胆木浸膏胶囊 |
| 克柔念珠菌 | 6 | 12 | 6 |
如图1所示，上面的滤纸片为氟康唑阳性对照，下面的滤纸片为胆木叶提 取物，上面的滤纸片中间是白色的，说明克柔念珠菌已经长到菌片上，说明氟 康唑的菌片(即滤纸片)已长菌，说明氟康唑没有抑菌效果，下面的菌片周围 有黑色的抑菌圈，抑菌圈直径为12mm，说明下面的菌片上呈现胆木叶提取物 溶液的褐色，说明胆木叶提取物菌片上没有长菌，说明胆木叶提取物具有抗克 柔念珠菌的作用。
克柔念珠菌对氟康唑天然耐药，克柔念珠菌对高浓度的氟康唑具有同样的 抑菌效果。
图2为胆木浸膏胶囊对克柔假丝酵母菌(Ck)的抑菌活性图，从图2中可 以看到，1号菌片为氟康唑阳性对照；2，3，4号菌片均为胆木浸膏胶囊，胆 木浸膏胶囊无黑色抑菌圈，菌片周围都长白了，说明菌片周围以及菌片上均长 满了菌，故胆木浸膏胶囊无抑菌效果。
胆木浸膏胶囊中的用药成分为胆木，胆木为茜草科植物乌檀Naucleaofficinalis Pierre.ex Pitard的枝、树皮。即胆木浸膏胶囊的用药部位不是本申请 中的胆木叶，从上述的抑菌实验可以看出，胆木无抑菌作用，而胆木叶具有抑 菌作用。
6微量稀释法抑菌试验：
6.1RPMI-1640培养基的制备：
分别称取10.4g RPMI-1640，34.5g MOPS，2.0g NaHCO3，置1000mL 容量瓶中，加超纯水适量使溶解，以1mol/L NaOH调节培养基pH至7.0±0.1， 超纯水定容至刻度。无菌条件下，以0.22μm微孔滤膜滤过，置4℃冰箱中保 存，备用。
6.2试液的准备，用时新制：
精密称取胆木叶提取物干膏及按生药量计算，分别以超纯水配制成3022 μg/mL的药液，高压灭菌后分别用RPMI-1640液体培养基进行对倍稀释配制， 得浓度分别为1510μg/mL、755μg/mL、377.5μg/mL、188.7μg/mL、94.4μg/mL、 47.2μg/mL、23.6μg/mL、11.8μg/mL、5.9μg/mL、3μg/mL的药液；放入离心 管架中，置4℃冰箱保存备用。
6.3试验内容：
菌悬液分两步稀释1000倍作为试验用菌液，试验设置分胆木叶提取物、 空白组及阴性对照组，无菌条件下，取96孔板按组别分别加入相应溶液，其 胆木叶提取物分别加入先前配制好的相应药液100μL及100μL试验用菌液， 空白组加入200μL RPMI-1640液体培养基，阴性对照组加入100μL RPMI-1640 液体培养基及100μL试验用菌液，加好药液和菌液后，适度振摇均匀，多功能 酶标仪波长450nm测定，记录数据为空白吸光度，放入37℃培养箱中培养48h 后再进行测定，记录数据为培养48h后吸光度，计算MIC值。
6.4最低抑菌浓度(MIC)以培养48h后各孔吸光度减去对应空白板各孔 吸光度得差值，将阴性对照组的平均差值计为100％的生长率，其值的1/2计 为50％的抑制率，实验组中平均差值最接近50％抑制率的对应浓度计为该药液 的MIC值。
6.5结果：具体见表3。
表3样品溶液对克柔念珠菌的MIC值(μg/mL)
| 样品 | 胆木叶提取物 |
| 克柔念珠菌 | 47.2 |
以上所述仅是本发明的优选实施方式，应当指出：对于本技术领域的普通 技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰， 这些改进和润饰也应视为本发明的保护范围。
Claims (7)
1.胆木叶提取物在制备抗克柔念珠菌药物中的应用。
2.根据权利要求1所述的应用，其特征在于，胆木叶提取物的制备方法为：精密称取胆木叶适量，乙醇回流提取，提取液浓缩，蒸干，得到胆木叶提取物。
3.根据权利要求2所述的应用，其特征在于，胆木叶提取物的制备方法为：精密称取胆木叶0.5g，65％乙醇50mL，70℃回流提取40min，提取液旋蒸仪浓缩，蒸干，得到胆木叶提取物。
4.根据权利要求1所述的应用，其特征在于，所述胆木叶提取物的最低抑菌浓度MIC为47.2μg/mL。
5.根据权利要求1所述的应用，其特征在于，所述抗克柔念珠菌药物选自口服给药剂型或外用给药剂型。
6.根据权利要求1所述的应用，其特征在于，所述口服给药剂型选自汤剂、颗粒剂、胶囊剂、片剂、口服液、丸剂、酊剂、糖浆剂。
7.根据权利要求1所述的应用，其特征在于，所述外用给药剂型选自凝胶剂、喷雾剂、软膏剂、贴剂、巴布剂、洗剂、乳膏剂、栓剂。
Priority Applications (2)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101138590A (zh) * | 2006-09-08 | 2008-03-12 | 邓世明 | 胆木叶在制备抗菌消炎药物中的用途 |
| CN101293038A (zh) * | 2007-04-24 | 2008-10-29 | 江苏康缘药业股份有限公司 | 胆木叶提取物及制备方法及其制剂与用途 |
| CN109125444A (zh) * | 2018-10-31 | 2019-01-04 | 戴姝君 | 胆木提取物的新应用 |
| CN111249197A (zh) * | 2020-03-11 | 2020-06-09 | 海南森祺制药有限公司 | 一种含胆木的中药组合物及其制备方法与应用 |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101138590A (zh) * | 2006-09-08 | 2008-03-12 | 邓世明 | 胆木叶在制备抗菌消炎药物中的用途 |
| CN101293038A (zh) * | 2007-04-24 | 2008-10-29 | 江苏康缘药业股份有限公司 | 胆木叶提取物及制备方法及其制剂与用途 |
| CN109125444A (zh) * | 2018-10-31 | 2019-01-04 | 戴姝君 | 胆木提取物的新应用 |
| CN111249197A (zh) * | 2020-03-11 | 2020-06-09 | 海南森祺制药有限公司 | 一种含胆木的中药组合物及其制备方法与应用 |
Non-Patent Citations (2)
| Title |
|---|
| WANG G , HOU L , WANG Y , ET AL.: "Two new neolignans and an indole alkaloid from the stems of Nauclea officinalis and their biological activities", pages 160 * |
| 高香奇等: "黎药裸花紫珠与胆木组合的药效学研究", vol. 26, no. 06, pages 34 - 38 * |
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