CN106620706A - L‑谷氨酸的新应用及其药物组合物 - Google Patents
L‑谷氨酸的新应用及其药物组合物 Download PDFInfo
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Abstract
本发明公开了L‑谷氨酸的新应用及其药物组合物，该药物组合物的活性成分包括非甾体抗炎药和L‑谷氨酸。非甾体抗炎药与L‑谷氨酸的药物组合物，既能发挥非甾体抗炎药的药理作用，又能降低其胃肠道不良反应，同时改善患者服药的顺应性。
Description
技术领域
本发明涉及药物化学技术领域，特别是涉及L-谷氨酸的新应用及其药物组合物。
背景技术
非甾体抗炎药(NSAIDs)是临床上广泛应用的药物，主要用于治疗炎症、疼痛及心血管疾病等。但非甾体抗炎药是环氧化酶抑制剂，可抑制***素的合成，使胃黏膜局部血流减少、黏液和黏膜屏障功能减弱，引起胃肠道损伤；另外，有些非甾体抗炎药如阿司匹林呈酸性，能直接导致胃黏膜损伤。非甾体抗炎药引起的溃疡具有潜在的危险，因为这种溃疡很少或没有任何症状，直至引起严重的胃肠道损伤。因此减少非甾体抗炎药的胃肠道副作用具有重要的现实意义。
发明内容
基于此，本发明提供一种对胃肠道具有保护作用的药物组合物。
具体的技术方案如下：
一种药物组合物，其活性成分包括非甾体抗炎药和L-谷氨酸(起胃肠道保护制剂的作用)。
在其中一些实施例中，所述非甾体抗炎药与L-谷氨酸的质量比为1:2-20。
在其中一些实施例中，所述非甾体抗炎药选自阿司匹林、布洛芬、萘普生、吲哚美辛、双氯芬酸或美洛昔康。
在其中一些实施例中，该药物组合物的剂型为缓释剂型。
在其中一些实施例中，该药物组合物的剂型为双释剂型，其中非甾体抗炎药部分为缓释或肠溶实体，L-谷氨酸部分为速释实体。
在其中一些实施例中，单位制剂中所述非甾体抗炎药的量为5-500mg，L-谷氨酸的量为100-2000mg。
本发明的另一目的是提供L-谷氨酸的新应用。
具体的技术方案如下：
L-谷氨酸(作为活性成分)在制备胃肠道保护制剂中的应用。
在其中一些实施例中，单位制剂中L-谷氨酸的量为100-2000mg。
本申请研究发现L-谷氨酸可减少或防止非甾体抗炎药对胃肠道的损伤。L-谷氨酸是食物蛋白质的重要组成，L-谷氨酸及其一钠盐是食物中主要的鲜味来源，L-谷氨酸一钠是味精的主要成分，其具体结构式如下：
L-谷氨酸可通过增强胃肠道的屏障作用、抑制非甾体抗炎药引起的氧化应激及促进损伤修复等过程，抑制非甾体抗炎药引起的胃肠道损伤。Jinap S等指出，没有充分的证据表明谷氨酸会引起哮喘及肥胖的不良反应，基于40多年大量的毒理学研究，认为谷氨酸在适量剂量范围内对包括孕妇、哺乳期妇女及儿童在内的一般人群是安全的(Jinap S,Hajeb P.Glutamate.Its applications in food and contribution to health[J].Appetite,2010,55(1):1-10)。因此谷氨酸长期使用的安全性较高，这将有利于非甾体抗炎药的长期用药。
非甾体抗炎药与L-谷氨酸为活性成分的抗炎护胃药物组合物，既能发挥非甾体抗炎药的药理作用，又能降低其胃肠道不良反应，同时改善患者服药的顺应性。
附图说明
图1为实施例1大鼠胃组织的溃疡指数比较柱状图；
具体实施方式
为了便于理解本发明，下面将本发明进行更全面的描述。但是，本发明可以以许多不同的形式来实现，并不限于本文所描述的实施例。相反地，提供这些实施例的目的是使对本发明的公开内容的理解更加透彻全面。
除非另有定义，本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的，不是旨在于限制本发明。本文所使用的术语“和/或”包括一个或多个相关的所列项目的任意的和所有的组合。
实施例1：L-谷氨酸对阿司匹林致大鼠慢性胃损伤的保护作用
实验方法：
72只雄性SD大鼠，购自长沙斯莱克景达实验动物有限公司。体重在180-220g范围内，随机分为9组，每组8只。分别为空白对照组(A组)、阿司匹林模型组(B组)、不同剂量L-谷氨酸保护组(C-H组)、阳性药盐酸雷尼替丁组(I组)。各组均灌胃给药，给予L-谷氨酸30min后给予阿司匹林，每次灌胃体积为1mL，共给药8天，每次灌胃前禁食8h，最后一次给药后禁食16h，用戊巴比妥钠腹腔注射麻醉，取胃，用冰生理盐水洗净，观察胃损伤状况，计算溃疡抑制率。
胃粘膜损伤指数测定：按Guth标准计算溃疡指数：斑点糜烂记1分；线状出血糜烂长度<1mm记2分；1-2mm记3分；2-4mm记4分；>4mm记5分，宽度>1mm时，分值×2。
溃疡指数抑制率(％)＝(对照组平均溃疡指数-治疗组平均溃疡指数)/对照组平均溃疡指数×100％。
表1实验动物分组及给药
实验结果：
表2L-谷氨酸对阿司匹林致大鼠慢性胃损伤的保护作用(Mean±SD,n＝8)
结果表明L-谷氨酸在100-800mg/kg剂量范围内能有效抑制阿司匹林导致的大鼠慢性胃损伤，且呈现剂量依赖性。
实施例2：复方阿司匹林/L-谷氨酸肠溶颗粒(1000袋)
(1)阿司匹林含药丸心的制备：
将阿司匹林与辅料过80目筛并混合均匀，以聚乙烯吡咯烷酮的醇/水溶液作黏合剂制备软材。采用挤出滚圆制粒。
(2)包肠溶衣层：
将处方量45％的水加热，将吐温80、单硬脂酸甘油酯、柠檬酸三乙酯加入热水中乳化，加入剩余量的水，放冷后倒入尤特奇分散体中，搅拌。将阿司匹林微丸置于流化床中，包肠溶衣层。
(3)L-谷氨酸微丸的制备：
将L-谷氨酸与辅料过80目筛并混合均匀，以5％的羟丙甲纤维素的水溶液做黏合剂制备软材。采用挤出滚圆制粒。将所制微丸在50℃干燥3h。
(4)将上述制备的阿司匹林肠溶微丸与L-谷氨酸微丸混合，按照处方量装袋。制成的复方颗粒剂单位制剂中含阿司匹林100mg，L-谷氨酸1000mg。
实施例3：复方布洛芬/L-谷氨酸片(1000片)
(1)处方组成：
(2)制备工艺：
将L-谷氨酸、布洛芬、预交化淀粉、微晶纤维素及羧甲基淀粉钠，过100目筛，混合均匀，以羟丙甲纤维素水溶液为黏合剂，制备软材，过20目筛制粒，60℃下干燥，20目筛整粒。加入硬脂酸镁，混合均匀，压片。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
Claims (8)
1.一种药物组合物，其特征在于，其活性成分包括非甾体抗炎药和L-谷氨酸。
2.根据权利要求1所述的药物组合物，其特征在于，所述非甾体抗炎药与L-谷氨酸的质量比为1:2-20。
3.根据权利要求1所述的药物组合物，其特征在于，所述非甾体抗炎药选自阿司匹林、布洛芬、萘普生、吲哚美辛、双氯芬酸或美洛昔康。
4.根据权利要求1-3任一项所述的药物组合物，其特征在于，该药物组合物的剂型为缓释剂型。
5.根据权利要求4所述的药物组合物，其特征在于，该药物组合物的剂型为双释剂型，其中非甾体抗炎药部分为缓释或肠溶剂型，L-谷氨酸部分为速释剂型。
6.根据权利要求1-3任一项所述的药物组合物，其特征在于，单位制剂中所述非甾体抗炎药的量为5-500mg，L-谷氨酸的量为100-2000mg。
7.L-谷氨酸在制备胃肠道保护制剂中的应用。
8.根据权利要求7所述的应用，其特征在于，单位制剂中L-谷氨酸的量为100-2000mg。
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