CN110538206A - 一种提取物在制备促胃溃疡胃黏膜愈合药中的用途 - Google Patents
一种提取物在制备促胃溃疡胃黏膜愈合药中的用途 Download PDFInfo
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Abstract
本发明属于植物药领域，提供了一种提取物在制备促胃溃疡胃黏膜愈合药中的用途。这种促胃溃疡胃黏膜愈合的中药提取物为厚叶牛耳草的精油提取物，提取方法为常压水蒸气蒸馏、减压水蒸气蒸馏或超临界CO2萃取。所述促胃溃疡胃黏膜愈合的中药提取物可以口服给药或者外用给药，以口服给药为佳。所述促胃溃疡胃黏膜愈合的中药提取物对多种原因引起的胃溃疡具有改善作用，促进溃疡黏膜愈合。所述促胃溃疡胃黏膜愈合的中药提取物可以与已知具有抗胃溃疡作用的中药提取物混合，组成复方提取物。
Description
技术领域
本发明属于植物药领域，特别涉及一种提取物在制备促胃溃疡胃黏膜愈合药中的用途。
背景技术
胃溃疡是一种病因复杂的胃黏膜损伤疾病。最初人们以为是胃酸过多、压力、应激、辛辣食物等因素导致的胃溃疡。那时人们普遍认为，在胃部酸性环境下，没有微生物能够存活。直至在胃中发现幽门螺杆菌后几十年，幽门螺杆菌与胃溃疡的关系才被接受。
实际上，胃酸的自身消化作用只是参与胃溃疡的因素之一，幽门螺杆菌、一些刺激胃肠道的药物、急性应激、胃运动异常和一些病毒都可以引发胃溃疡。其中可以诱发胃溃疡的药物常见的包括非甾体类抗炎药物、红霉素和一些抗癌药物。非甾体类抗炎药物可以引起胃溃疡，却不引发十二指肠溃疡。一般认为十二指肠溃疡是胃酸引起，非甾体类抗炎药不影响胃酸分泌，所以不会导致十二指肠溃疡。而非甾体类抗炎药物可以引起胃溃疡是因为药物对COX-1的抑制导致胃血管收缩，黏液细胞供血减少，胃黏膜屏障减弱，从而引起胃溃疡。在胃溃疡的具体进展中，一些促炎症因子如白介素、肿瘤坏死因子、核因子-kB也参与了胃溃疡的进展。
上消化道出血是胃溃疡常见的并发症，一般发生在溃疡出现后的1～2年内，出血多数自行停止。上消化道出血严重的应当进行止血处理，包括内镜下止血和使用止血药物。
在胃溃疡的治疗中经常采用硫糖铝等胃黏膜保护药物、抑制胃酸分泌的奥美拉唑等质子泵抑制剂和甲氰咪胍等H2受体拮抗剂、阿莫西林等抗幽门螺杆菌的抗生素。中医理论下，胃溃疡属于“胃脘痛”、“肝胃气痛”、“吞酸”等。中医常采用当归建中汤、左金丸、小柴胡汤等治疗胃溃疡。实验证实当单一中药或者复方中药抗胃溃疡与抑制胃酸分泌、促进局部血液微循环、抗幽门螺杆菌、促进黏膜细胞再生和增殖等作用有关，涉及的信号途径包括Wnt、JNK、NF-kB等。比如柴胡中的柴胡皂苷能够抑制NF-kB，降低乙醇诱导的胃溃疡；蒌叶醇提物可以抗吲哚美辛所致胃溃疡，并抑制JNK信号通路；乳香提取物能提激活Wnt信号通路，提高提高溃疡愈合质量。天然植物提取物在胃溃疡的治疗中优势明显，而且不良反应低于西药。
厚叶牛耳草是苦苣苔科植物厚叶旋蒴苣苔的全草，水煎煮液有滋补强壮、止血、止咳的功能，用于治肝脾虚弱、劳伤吐血、内伤咯血、肺病咳喘、白带，无名肿毒等，现被用于胆囊炎、支气管炎、宫颈糜烂、小儿黄疸等。
发明内容
针对以上的背景，本发明的目的是提供一种提取物的新的用途。具体来说是，一种提取物在制备抗胃溃疡药中的用途。
本发明的具体内容如下：
厚叶牛耳草提取物在制备抗胃溃疡药中的用途。具体来说是，厚叶牛耳草提取物在制备促胃溃疡胃黏膜愈合药中的用途。其中“促胃溃疡胃黏膜愈合药”指的是胃黏膜保护药或促进胃黏膜细胞再生、增殖进而促进胃溃疡愈合的药，而不是用于胃溃疡出血并发症的药。
其中厚叶牛耳草提取物为厚叶牛耳草的精油提取物。这种精油提取物具有抗溃疡作用和对胃溃疡后的胃黏膜愈合具有促进作用。
其中厚叶牛耳草的精油提取物采用水蒸气蒸馏法提取或超临界CO2萃取法提取。
前述的水蒸气蒸馏法提取包括常压水蒸气蒸馏法提取和减压水蒸气蒸馏法提取。
其中常压水蒸气蒸馏法提取的方法为：
取干燥厚叶牛耳草，粉碎过20～40筛，按照料液比1:（8～12）的比例加水浸泡1～5小时，75℃下水蒸气蒸馏提取6～10小时，收集馏出液无水硫酸钠脱水，收集精油。优选的方案是：取干燥厚叶牛耳草，粉碎过30筛，按照料液比1:12的比例加水浸泡3小时，75℃下水蒸气蒸馏提取8小时，收集馏出液无水硫酸钠脱水，收集精油。
其中减压水蒸气蒸馏法提取的方法为：取干燥厚叶牛耳草，粉碎过20～40筛，按照料液比1:（8～12）的比例加水浸泡1～5小时，0.08～0.09Mpa下收集55～80℃的馏出液；馏出液加入NaCl盐析后乙醚萃取，萃取液无水硫酸钠脱水，过滤，滤液旋蒸后收集精油。优选的方案是：取干燥厚叶牛耳草，粉碎过30筛，按照料液比1: 12的比例加水浸泡3小时，0.085Mpa下收集55～80℃的馏出液；馏出液加入NaCl盐析后乙醚萃取，萃取液无水硫酸钠脱水，过滤，滤液旋蒸后收集精油。
其中超临界CO2萃取法提取的方法为：取干燥厚叶牛耳草，粉碎过40～60筛；将药材粉末置于超临界流体萃取装置中；萃取釜压力15～25Mpa、萃取釜温度40～60℃；分离釜I和分离釜II的压力为6MPa，分离釜I和分离釜II的温度依次为50℃、40℃；CO2流量10L/小时，萃取2小时，收集萃取物。优选的方案是，取干燥厚叶牛耳草，粉碎过50筛；将药材粉末置于超临界流体萃取装置中；萃取釜压力15Mpa、萃取釜温度55℃；分离釜I和分离釜II的压力为6MPa，分离釜I和分离釜II的温度依次为50℃、40℃；CO2流量10L/小时，萃取2小时，收集萃取物。
前述的厚叶牛耳草提取物可以与已知的抗胃溃疡中药提取物混合，形成复方提取物用于胃溃疡的治疗，从而进一步提高抗溃疡效果。这些已知的抗胃溃疡中药提取物包括但不限于白芨提取物、黄芪提取物、白术提取物、火索麻提取物、黄连和吴茱萸混合提取物等等。
作为单一药材提取物使用时，可以作为口服精油服用，也可以把精油通过羟丙基-β-环糊精包合后作为溶液口服或者将环糊精包合的精油干燥后以固体形式掺入辅料制成口服的片剂、颗粒剂等等。
具体实施方式
下面是本发明的具体实施例。通过实施例对本发明进行说明。
实施例1 厚叶牛耳草精油的常压水蒸气蒸馏法提取
取干燥厚叶牛耳草6kg，粉碎过30筛，按照料液比1:12的比例加水浸泡3小时，75℃下水蒸气蒸馏提取8小时，收集馏出液无水硫酸钠脱水，收集精油。
实施例2厚叶牛耳草精油的减压水蒸气蒸馏法提取
取干燥厚叶牛耳草6kg，粉碎过30筛，按照料液比1: 12的比例加水浸泡3小时，0.085Mpa下收集55～80℃的馏出液；馏出液加入NaCl盐析后乙醚萃取，萃取液无水硫酸钠脱水，过滤，滤液旋蒸后收集精油。
实施例3厚叶牛耳草精油的超临界CO2萃取
取干燥厚叶牛耳草，粉碎过50筛；将药材粉末置于超临界流体萃取装置中；萃取釜压力15Mpa、萃取釜温度55℃；分离釜I和分离釜II的压力为6MPa，分离釜I和分离釜II的温度依次为50℃、40℃；CO2流量10L/小时，萃取2小时，收集萃取物。
实施例4 厚叶牛耳草精油对吲哚美辛诱导胃溃疡的抑制作用
按照实施例1、2、3的方法制备不同的厚叶牛耳草精油作为实验药物，以纯净水为对照。
雄性小白鼠，18～22g，小鼠随机分为4组，每组6只，模型组灌胃纯净水，每日灌胃0.3mL；给药组分别灌胃常压水蒸气蒸馏、减压水蒸气蒸馏或超临界CO2萃取所得精油，每日灌胃0.3mL；各组小鼠连续灌胃给药7日。末次给药后禁食禁水3小时，将吲哚美辛溶于4%的二甲基亚砜-玉米油混合液，每只小鼠灌胃吲哚美辛0.4mg。
吲哚美辛灌胃后4小时，处死小鼠，取胃，甲醛固定，切开冲洗胃内容物，测量溃疡部位的长度和宽度，取最大长度和垂直于最大长度所在轴的最长部分作为长度和宽度，以溃疡面积S=长度X宽度。各组小鼠胃溃疡面积统计结果见表1。
表1小鼠胃溃疡面积
*：与模型组相比P<0.01。
小鼠溃疡面积分析结果表明，三种提取方式获得的厚叶牛耳草精油对吲哚美辛诱导的小鼠胃溃疡具有抑制作用。超临界萃取的厚叶牛耳草精油有优于常压蒸馏的趋势。
实施例5 厚叶牛耳草精油对酸刺激性胃溃疡的抑制作用
按照实施例1、2、3的方法制备不同的厚叶牛耳草精油作为实验药物，以纯净水为对照。
大白鼠，雄性，200～220g。大鼠麻醉仰卧固定，腹部备皮，消毒铺巾，剑突下行腹部纵切口暴露鼠胃，以直径5mm的长玻璃管垂直置于胃窦前壁浆膜面，向管内滴入0.2mL的冰醋酸。15分钟后棉签擦拭，并生理盐水冲洗接触部位，将胃还纳腹腔，逐层关腹，缝合消毒。
术后将大鼠随机分为4组，每组6只。模型组灌胃纯净水，每日灌胃0.8mL；给药组分别灌胃常压水蒸气蒸馏、减压水蒸气蒸馏或超临界CO2萃取所得精油，每日灌胃0.8mL；各组小鼠连续灌胃给药14日。
末次给药4 h 后，处死各组大鼠，取鼠胃，甲醛固定，切开冲洗胃内容物，测量溃疡部位的长度和宽度，取最大长度和垂直于最大长度所在轴的最长部分作为长度和宽度，以溃疡面积S=长度X宽度。各组大鼠胃溃疡面积统计结果见表2。
表2大鼠胃溃疡面积
*：与模型组相比P<0.05；**：与模型组相比P<0.01。
大鼠溃疡面积分析结果表明，三种提取方式获得的厚叶牛耳草精油对冰醋酸诱导的大鼠胃溃疡具有抑制作用。减压蒸馏和超临界萃取的厚叶牛耳草精油有优于常压蒸馏的趋势。
以上实施例给出了本发明的部分实施方式和说明。以上实施例是用于对本发明方案的解说而不是限制本发明的保护范围。
Claims (10)
1.在一种提取物在制备促胃溃疡胃黏膜愈合药中的用途，其特征在于，所述提取物为厚叶牛耳草提取物。
2.根据权利要求1所述的用途，其特征在于，所述提取物为厚叶牛耳草的精油提取物。
3.根据权利要求2所述的用途，其特征在于，所述精油提取物采用水蒸气蒸馏法提取。
4.根据权利要求3所述的用途，其特征在于，所述精油提取物采用常压水蒸气蒸馏法提取。
5.根据权利要求4所述的用途，其特征在于，所述精油提取物的制备方法为：取干燥厚叶牛耳草，粉碎过20～40筛，按照料液比1:（8～12）的比例加水浸泡1～5小时，75℃下水蒸气蒸馏提取6～10小时，收集馏出液无水硫酸钠脱水，收集精油。
6.根据权利要求3所述的用途，其特征在于，所述精油提取物采用减压水蒸气蒸馏法提取。
7.根据权利要求5所述的用途，其特征在于，所述精油提取物的制备方法为：取干燥厚叶牛耳草，粉碎过20～40筛，按照料液比1:（8～12）的比例加水浸泡1～5小时，0.08～0.09Mpa下收集55～80℃的馏出液；馏出液加入NaCl盐析后乙醚萃取，萃取液无水硫酸钠脱水，过滤，滤液旋蒸后收集精油。
8.根据权利要求2所述的用途，其特征在于，所述精油提取物采用超临界CO2萃取法提取。
9.根据权利要求8所述的用途，其特征在于，所述精油提取物的制备方法为：取干燥厚叶牛耳草，粉碎过40～60筛；将药材粉末置于超临界流体萃取装置中；萃取釜压力15～25Mpa、萃取釜温度40～60℃；分离釜I和分离釜II的压力为6MPa，分离釜I和分离釜II的温度依次为50℃、40℃；CO2流量10L/小时，萃取2小时，收集萃取物。
10.根据权利要求9所述的用途，其特征在于，萃取釜压力为15 Mpa，萃取釜温度为55℃。
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