CN116077610A - 缓解酒精性肝损伤的中药组合物、其制备方法及其应用 - Google Patents
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Abstract
本发明涉及中药组合物技术领域，具体而言，涉及缓解酒精性肝损伤的中药组合物、其制备方法及其应用。以重量份计，中药组合物的原料包括葛根25‑35份、木瓜25‑35份、乌梅25‑35份、干姜5‑15份、砂仁5‑15份、丁香5‑15份和甘草4‑8份。该中药组合物能有效预防、缓解和/或治疗酒精干预所致的肝肠损伤，为酒精干预所致的肝肠损伤的防治提供更多的方案和可能性。
Description
技术领域
本发明涉及中药组合物技术领域，具体而言，涉及缓解酒精性肝损伤的中药组合物、其制备方法及其应用。
背景技术
酒精性肝损伤(ALD)是长期饮酒的结果，其主要特征是脂肪变性，坏死和肝细胞再生减少，最终导致肝硬化和肝癌。慢酒精摄入还会导致酒精性肝损伤患者的肠道微生物群失调、肠道屏障功能障碍、炎症和免疫失等。此外，细菌代谢物脂多糖(LPS)含量的变化也影响肠屏障层的完整性。饮酒可增加LPS水平，LPS与肝脏Kupffer细胞上的Toll样受体4(TLR4)及其共受体CD14相互作用，导致核因子(NF-κB)通过髓样分化初级反应88(MyD88)途径激活Kupffers细胞。NF-κB的激活导致核内NF-κB p65的移位，从而上调促炎细胞因子(例如肿瘤坏死因子α；TNF-α)的水平，并加速炎性细胞的浸润，导致肝脏的氧化损伤、肝细胞坏死和肠道屏障功能障碍。尽管ALD严重危害人体健康，但目前预防ALD的满意治疗方法有限。因此需要寻找新的安全有效的药物来预防、缓解和治疗ALD。
鉴于此，特提出本发明。
发明内容
本发明的目的在于提供缓解酒精性肝损伤的中药组合物、其制备方法及其应用。本发明实施例提供的中药组合物能有效预防、缓解和/或治疗酒精干预所致的肝肠损伤，为酒精干预所致的肝肠损伤的防治提供更多的方案和可能性。
本发明是这样实现的：
第一方面，本发明提供一种缓解酒精性肝损伤的中药组合物，以重量份计，其原料包括葛根25-35份、木瓜25-35份、乌梅25-35份、干姜5-15份、砂仁5-15份、丁香5-15份和甘草4-8份。
在可选的实施方式中，以重量份计，其原料包括葛根30份、木瓜30份、乌梅30份、干姜9份、砂仁9份、丁香9份和甘草6份。
第二方面，本发明提供一种前述实施方式所述的缓解酒精性肝损伤的中药组合物的制备方法，包括：对葛根、木瓜、乌梅、干姜、砂仁、丁香和甘草进行处理后混合。
在可选的实施方式中，包括：对所述葛根、所述木瓜、所述乌梅和所述甘草进行提取形成提取混合物；
将所述砂仁、所述干姜和所述丁香进行粉碎形成粉碎料，而后将所述提取混合物与所述粉碎料混合。
在可选的实施方式中，将所述葛根、所述木瓜、所述乌梅、所述甘草和水混合后进行煎煮形成煎煮液，而后浓缩形成干膏粉；
将所述砂仁、所述干姜和所述丁香粉碎至粒径小于45μm的超微粉，而后将所述干膏粉与上述超微粉混合。
第三方面，本发明提供一种中药制剂，其包括前述实施方式所述的缓解酒精性肝损伤的中药组合物。
在可选的实施方式中，所述中药制剂还包括辅料。
在可选的实施方式中，所述中药制剂的剂型包括固体制剂。
在可选的实施方式中，固体制剂包括片剂和粉末；优选包括咀嚼片和素片。
第四方面，本发明提供一种利要求1所述的缓解酒精性肝损伤的中药组合物或前述实施方式所述的中药制剂在制备治疗、预防和/或缓解酒精干预所致的肝肠损伤的药物中的应用。
本发明具有以下有益效果：本发明实施例通过葛根、木瓜、乌梅、干姜、砂仁、丁香和甘草配合采用特定的配比形成中药组合物，该组合物能有效预防、缓解和/或治疗酒精干预所致的肝肠损伤，为酒精干预所致的肝肠损伤的防治提供更多的方案和可能性。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对实施例中所需要使用的附图作简单地介绍，应当理解，以下附图仅示出了本发明的某些实施例，因此不应被看作是对范围的限定，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他相关的附图。
图1为本发明实施例4提供的咀嚼片的示意图；
图2为本发明实施例5提供的素片的示意图；
图3为本发明实施例6提供的固体饮料的示意图；
图4为本发明实施例提供的质量检测的高效液相图；
图5为本发明实验例提供的药物对体重的影响结果图；
图6为本发明实验例提供的药物对肝脏病理形态的影响结果图；
图7为本发明实验例提供的药物对小鼠血生化的影响结果图；
图8为本发明实验例提供的药物对小鼠氧化应激的影响结果图；
图9为本发明实验例提供的药物对小鼠炎症水平的影响结果图；
图10为本发明实验例提供的药物对小鼠肝脏TLR4介导的NF-κB信号通路的影响结果图；
图11为本发明实验例提供的药物对小鼠肠上皮细胞染色结果图；
图12为本发明实验例提供的药物对小鼠occludin、claudin-4和ZO-1的蛋白影响结果图。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，下面将对本发明实施例中的技术方案进行清楚、完整地描述。实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过市售购买获得的常规产品。
本发明实施例提供中药组合物，其能够有效预防、缓解和/或治疗酒精干预所致的肝肠损伤。具体地，以重量份计，其原料包括葛根25-35份、木瓜25-35份、乌梅25-35份、干姜5-15份、砂仁5-15份、丁香5-15份和甘草4-8份。例如，葛根25份、木瓜25份、乌梅25份、干姜5份、砂仁5份、丁香5份和甘草4份；葛根35份、木瓜35份、乌梅35份、干姜15份、砂仁15份、丁香15份和甘草8份；葛根35份、木瓜25份、乌梅32份、干姜15份、砂仁5份、丁香15份和甘草7份；葛根30份、木瓜30份、乌梅30份、干姜9份、砂仁9份、丁香9份和甘草6份。
本发明实施例提供的组合物中葛根味甘、辛，能生津止渴、解酒毒，可用治酒毒伤中，恶心呕吐，脘腹痞满等，为君药。木瓜温香入脾，能化湿和胃，湿去则中焦得运；味酸入肝，舒筋活络而缓挛急，治疗湿阻中焦之腹痛吐泻转筋。乌梅酸、涩、平，具有敛肺，涩肠，生津。两药配合共为臣药以助君药生津止渴，和胃止呕。砂仁辛散温通，具有化湿醒脾开胃，行气温中之佳效，可温中暖胃以达止呕止泻之功。丁香辛温芳香，暖脾胃而行气滞，尤善降逆，故有温中散寒，降逆止呕、止呃之功，为治疗胃寒呕吐呃逆之要药，配合共为佐药以化湿行气，开胃醒脾，加强君药解酒毒之功。甘草性甘平，药性和缓，与寒热补泻各类药物同用，能缓和烈性或减轻毒副作用，有调和诸药之功。诸药合用共奏壮脾进食、有解酒护肝之功效。
上述中药组合物可以直接以全药或者提取物的方式入药，也可以与现有的辅料混合入药。入药方式可以是制备为具有剂型的中药制剂，具体地，该中药制剂可以包括固体制剂，例如片剂和粉末；优选包括咀嚼片和素片。
上述中药组合物的制备包括：对所述葛根、所述木瓜、所述乌梅和所述甘草进行提取形成提取混合物；将所述砂仁、所述干姜和所述丁香进行粉碎形成粉碎料，而后将所述提取混合物与所述粉碎料混合。
具体地，将所述葛根、所述木瓜、所述乌梅、所述甘草和水混合后进行煎煮形成煎煮液，而后浓缩形成干膏粉；将所述砂仁、所述干姜和所述丁香粉碎至粒径小于45μm的超微粉，而后将所述干膏粉与上述超微粉混合。
以下结合实施例对本发明的特征和性能作进一步的详细描述。
实施例1
本实施例提供一种中药组合物，其原料包括葛根30g、木瓜30g、乌梅30g、干姜9g、砂仁9g、丁香9g和甘草6g。
本实施例提供一种上述中药组合物的制备方法，包括：
分别将药材葛根、木瓜、乌梅、甘草、砂仁、干姜和丁香粉碎，按药方比例取粉碎后的药材(葛根、木瓜、乌梅、甘草)，10倍量超纯水浸泡30min后进行煎煮提取3次，每次煎煮30min，合并提取液，过滤，60℃减压回收，得到干膏粉，称重。
将砂仁、干姜、丁香药材粉净制，分别进行二次粉碎，粉碎成粒径小于45um的超微粉。
将上述干膏粉质量换算成生药质量，再按药方比例与砂仁、干姜、丁香超微粉混合，环氧乙烷灭菌，得上述中药组合物(下文称为制剂原料)。
实施例2
本实施例提供一种中药组合物，其原料包括葛根35g、木瓜25g、乌梅32g、干姜15g、砂仁5g、丁香15g和甘草7g。
其制备方法与实施例1相同。
实施例3
本实施例提供一种中药组合物，其原料包括葛根25g、木瓜25g、乌梅25g、干姜5g、砂仁5g、丁香5g和甘草4g。
其制备方法与实施例1相同。
实施例4
将实施例1提供的中药组合物制备为咀嚼片，具体如下：
分别取实施例1的制剂原料28.20g、山梨糖醇10.94g、硬脂酸镁0.60g、清凉剂0.12g、安赛蜜0.08g、三氯蔗糖0.06g混合均匀后压制成1克/片即得咀嚼片，参见图1。
实施例5
将实施例1提供的中药组合物制备为素片，具体如下：
分别取实施例1的制剂原料28.20g、山梨糖醇7.90g、麦芽糊精3.00g、硬脂酸镁0.60g混合均匀后压制成1g/片即得素片，参见图2。
实施例6
将实施例1提供的中药组合物制备为固体饮料，具体如下：
分别取实施例1的制剂原料28.20g、山梨糖醇11.00g、麦芽糊精10.00g、安赛蜜0.30g、三氯蔗糖0.50g混合均匀，装袋，每袋5g。参见图3。
质量检测
(1)检测样品：实施例1制备得到的制剂原料
(2)葛根素和柠檬酸含量测定
葛根素对照品溶液的制备：精密称取葛根素对照品0.0016g，用30％甲醇定容到10mL，制成1mL含0.16mg葛根素的溶液，即得。
供试品溶液a的制备：取上述所得制剂原料约0.02g，用30％甲醇定容到25mL，称重，超声30min，放冷，以30％甲醇补足重量，摇匀，取适量过0.45μm微孔滤膜，备用。
柠檬酸对照品溶液的制备：精密称取柠檬酸对照品0.0087g，用超纯水定容到10mL，制成每1mL含0.87mg柠檬酸的溶液，即得。
供试品溶液b的制备：取实施例1的干制剂原料约0.02g，用超纯水定容到10mL，称重，超声30min，放冷，以超纯水补足重量，摇匀，取适量过0.45μm微孔滤膜，备用。
色谱条件：
色谱柱：Waters symmetry column C18柱4.6mm×250mm 5μm；葛根素流动相：甲醇-0.1％磷酸水(25：75)，检测波长254nm，流速：1.0mL·min-1，进样体积：10μL；理论塔板数：以葛根素峰计算不低于4000。柠檬酸流动相：甲醇-0.1％磷酸水(1：99)，检测波长：210nm，流速：1.0mL·min-1，进样体积：10μL。理论塔板数：以柠檬酸峰计算不低于7000。
(3)结果
高效液相色谱结果图参见图4，线性回归方程见表1，图4中1为葛根素，2为柠檬酸，3为供试品溶液a，4为供试品溶液b。
表1线性回归方程
可见，制剂原料中葛根素含量为1.37％，柠檬酸含量为6.41％。
实验例
(1)试剂以及仪器
试剂：小鼠肿瘤坏死因子α(TNF-α)、白介素6(IL-6)酶联免疫(ELISA)测定试剂盒(伊诺瓦(武汉)生物有限公司)；小鼠白介素1β(IL-1β)酶联免疫(ELISA)测定试剂盒、丙二醛(MDA)、还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)测定试剂盒(南京建成生物研究所)；无水乙醇、多聚甲醛(国药集团化学试剂有限公司)，谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)测定试剂盒(深圳迈瑞生物医疗电子股份有限公司)；BCA蛋白浓度测定试剂盒(上海碧云天生物科技有限公司)；水飞蓟宾胶囊(天津天士力圣特制药有限公司)。
仪器：全自动生化分析仪(迈瑞科技有限公司)，高速低温组织研磨仪(中国Servicebio公司)，高速冷冻离心机(美国SCILOGEX)，酶标仪(Molecular Devices公司)，电子天平(先行者电子天平)。
(2)实验动物分组
雄性昆明种小鼠60只(SPF级)(6周龄，20±2g)，购自湖北省实验动物研究中心。实验单位使用许可证编号：SCXK-(鄂)2021-0089，实验动物生产许可证编号：SCXK-(鄂)2020-0018。合格证编号：42000600047709。小鼠饲养于SPF级动物房内，适应性喂养一周后分为6组，每组10只：正常对照组(NC)，酒精性肝损伤模型组(MC，10mL·kg-1)，阳性药对照组(PC，0.0273g·kg-1)，中药组合物低、中、高剂量组(1、3、9g生药·kg-1，组合物命名为YSTY)。
(3)给药
受试药：根据预实验结果将低、中、高剂量设为1、3、9g生药·kg-1·BW。临用时，用生理盐水按所需剂量将实施例1的中药组合物配成合适浓度的药液备用。
阳性对照药：水飞蓟宾胶囊，根据药品说明书人用量一般为210mg·d-1，按照体表面积折算，小鼠用量为210×0.0026mg/0.02kg＝0.0273g·kg-1。
将上述小鼠每日给药1次，连续给药4周，其中正常对照组、模型组给予等容量的生理盐水。其中第3周开始，除正常对照组外，每次给药4h后每只小鼠灌胃10mL·kg-1造模药(30％的乙醇)，连续造模2周。第四周的最后一天采集小鼠粪便，并将所收集粪便冻存在-80℃备用。所有小鼠实验结束前一天禁食不禁水12h。给药4周后，小鼠摘眼球取血，颈椎脱臼处死小鼠，取肝脏、心脏、脾脏、肺、肾脏、回肠组织，其中肝脏、心脏、脾脏、肺、肾、胃称重，用液氮速冻后，置于-80℃冰箱保存，部分肝脏、回肠组织用4％多聚甲醛中固定，用于石蜡包埋及苏木精和曙红(H&E)染色后观察病理变化。
(4)血清生化指标测定
采集的血液以3000rpm，4℃离心15min，取上清。血清在-80℃下保存直到测量。采用全自动生化分析仪测定血清中ALT、AST、TC和TG水平。
(5)肝组织中氧化应激因子MDA、CAT、GSH和SOD的测定
肝组织和生理盐水按照1：9的比例混合后充分研磨，2500rpm下离心10分钟后取上清液，按照检测试剂盒说明书步骤依次测定MDA、CAT、GSH和SOD活性。
(6)肝组织中炎症因子IL-6、IL-1β和TNF-α的测定
肝组织和生理盐水按照1：9的比例混合后充分研磨，2500rpm下离心10分钟后取上清液，按照检测试剂盒说明书流程依次测定小鼠血清炎症因子IL-6、IL-1β和TNF-α的含量。
(7)蛋白质免疫印迹
将肝脏和回肠组织从-80℃冰箱取出，根据细胞核和细胞浆蛋白提取试剂盒说明书操作，加入试剂充分研磨后在冰上裂解20min，接着以1500g离心5min，收集上清液,使用BCA蛋白检测试剂盒测定蛋白浓度。根据目的蛋白分子量大小配制浓度为10％的SDA-PAGE凝胶电泳，按照上层胶80V/25min、下层胶120V/60min的电泳条件分离蛋白条带，后用湿法转膜120V/1.5h，用脱脂奶粉室温摇床封闭2h。接着用TBST洗去多余的蛋白，分别洗5次、每次5min。然后加入相应的一抗，在4℃冰箱摇床孵育过夜。接着用TBST洗膜5次，每次5min，后加入二抗室温摇床孵育1.5h，TBST洗膜5次，每次5min，最后加入ECL发光液，通过凝胶成像系统曝光，并用ImageJ软件进行光密度值分析。肝脏细胞质蛋白和回肠组织蛋白以GAPDH为内参，肝脏细胞核蛋白以Histone H3为内参。
(8)统计学分析
数据均以平均数±标准误(Mean±SEM)表示，采用GraphPad Prism8.0软件进行单因素方差分析(ANOVA)，显著性差异使用*P＜0.05，**P＜0.01，***P＜0.001和#P＜0.05，##P＜0.01，###P＜0.001表示。
(9)结果
(A)药物对体重的影响
结果参见图5，其为小鼠每周体重增长率变化，数据为小鼠不同时间点体重相对第一天体重的增长率；**P<0.01与MC相比；##P<0.01与NC相比；n＝10。
根据图5可知，药物干预前两周6组小鼠体重增长迅速，第二周酒精干预后，与NC组相比，PC、MC、1g/kg、3g/kg组体重增长速率均表现出不同程度抑制，其中MC组体重增长抑制最明显，9g/kg组无明显体重增长抑制，说明酒精干预抑制了小鼠体重的增长，而给药后逆转了这种现象。
(B)药物对肝脏病理形态的影响
结果参见图6，其为肝脏组织切片，肝组织H&E染色结果显示MC组肝窦紊乱，淋巴细胞浸润明显，肝细胞肿胀，肝细胞部分变性坏死，这些变化通过受试药治疗得到很大缓解。
(C)药物对脏器指数影响
结果见表2。
表2中药组合物对小鼠脏器指数的影响(脏器/体重，％)
根据上表可知，与NC组相比，MC组的肝脏指数、胃指数和肾脏指数分别显著升高了0.68％、0.18％和0.10％，而心脏、肺和脾的体重指数无显著变化。这可能是因为酒精暴露会导致机体代谢能力下降，引起肝脏、胃、肾的肿大。这些由酒精引起的增加可以通过药物的治疗所阻止。与MC组相比，给药后ALD小鼠肝脏指数(p＜0.01)、胃指数、肾脏指数(p＜0.01)降低，但不能恢复至正常组水平。药方对心、肺、脾也有微弱的改善作用，但无统计学差异。
(D)药物对小鼠血生化的影响
结果参见图7，其中，A、B、C和D分别依次为肝组织中AST、ALT、TC、TG水平。n＝10，与NC组相比，##P<0.01；与MC组相比，**P<0.01或P<0.001。
根据图7可知，与NC组相比，MC组中ALT和AST的含量升高(均P<0.01)，说明ALD小鼠产生了急性肝细胞损伤，水飞蓟宾和组合物干预后可以不同程度的降低ALD小鼠肝血清ALT(P<0.01或P<0.001)和AST含量，说明组合物能剂量依赖性地逆转ALD小鼠肝损伤，恢复肝功能。与NC组相比，MC组小鼠血清TC和TG(p＜0.01)含量显著升高，说明酒精干预后MC组小鼠肝脏脂肪代谢紊乱。药物干预后小鼠TC和TG含量下降，说明药物在一定程度改善小鼠血脂代谢紊乱。
(E)药物对小鼠氧化应激的影响
结果参见图8，其中，A、B、C和D分别依次为肝组织中MDA、CAT、GSH、SOD水平。n＝10，与NC组相比，##P<0.01；与MC组相比，**P<0.01。
根据图8可知，酒精干预引起肝脏严重的氧化应激损伤，MC组小鼠肝组织中MDA水平明显地高于NC组(P<0.01)；给药组组MDA水平较酒MC组显著降低(P<0.01)；MC组小鼠肝组织中CAT、GSH水平明显地低于NC组(均P<0.01)；给药组CAT、GSH水平较MC组显著升高(均P<0.01)，且与给药剂量呈正相关，但不能恢复到正常组水平。说明组合物在一定程度上改善改善ALD小鼠氧化应激损伤。
(F)药物对小鼠炎症水平的影响
结果参见图9，其中，n＝10，与NC组相比，##P<0.01；与MC组相比，**P<0.01或***P<0.001)。
根据图9可知，MC组小鼠肝组织IL-6、IL-1β、TNF-α的含量均显著升高(P<0.01或P<0.001)，说明机体产生了炎症反应。而水飞蓟宾或和组合物干预后ALD小鼠肝组织中IL-6、IL-1β、TNF-α水平均显著下降(P<0.01或P<0.001)，肝脏内炎症水平降低。
(G)药物对小鼠肝脏TLR4介导的NF-κB信号通路的影响
NF-κB是炎性反应启动调节的关键核因子。正常情况下，NF-κB与其抑制蛋白IκBα结合以失活状态存在于细胞质中，当机体受到促炎因子如TNF-α、LPS、ROS等刺激时，IIκBα磷酸化及降解，NF-κB被活化，NF-κB进入细胞核内启动信号转导通路，继而产生大量炎症因子。
结果见图10，其中，n＝3，与NC组相比，##P<0.01或###P<0.001；与MC组相比，*P<0.05或**P<0.01或***P<0.001。
根据图10所示，免疫印迹法结果显示，与NC组相比，MC组核因子p65的蛋白水平因乙醇暴露而显著升高(P<0.01)，ALD小鼠肝组织中TLR4、CD14和MyD88的蛋白水平因酒精干预而显著升高(均P<0.01)，胞质p65、IKBα的表达降低(均P<0.01)，水飞蓟宾或和组合物干预后抑制了ALD小鼠肝组织中TLR4、CD14和MyD88蛋白水平的增强表达，提高了IKBα的表达水平。这些变化说明ALD小鼠发生了肝脏内发生了炎症反应，组合物可以通过TLR4介导的NF-κB信号通路降低肝脏炎症水平，恢复肝功能。
(H)药物对小鼠肠屏障功能的影响
结果参见图11和图12，其中图11中的A、B、C、D、E和F分别依次为NC、MC、PC、1、3和9(g/kg BW)组。图12中n＝3，与NC组相比，##P<0.01；与MC组相比，*P<0.05或**P<0.01。
根据图11可知，MC组肠上皮细胞间紧密连接破坏，肠绒毛不规则且较短，绒毛缺失，隐窝扭曲，组合物治疗后绒毛损伤减少、隐窝无明显结构异常。
根据图12可知，与NC组相比，MC组回肠组织occludin、claudin-4和ZO-1的蛋白含量显著下降(均P<0.01)，说明ALD小鼠肠道屏障结构可能被损坏，并且肠道内发生了炎症反应。水飞蓟宾和或组合物治疗后显著提高ALD小鼠中occludin、claudin-4和ZO-1蛋白水平(P<0.01或P<0.001)。这些发现表明，组合物可以通过恢复occludin、claudin-4和ZO-1蛋白的表达，降低肠道炎症水平，并增加ALD小鼠肠道屏障的完整性。
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，对于本领域的技术人员来说，本发明可以有各种更改和变化。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (10)
1.一种缓解酒精性肝损伤的中药组合物，其特征在于，以重量份计，其原料包括葛根25-35份、木瓜25-35份、乌梅25-35份、干姜5-15份、砂仁5-15份、丁香5-15份和甘草4-8份。
2.根据权利要求1所述的缓解酒精性肝损伤的中药组合物，其特征在于，以重量份计，其原料包括葛根30份、木瓜30份、乌梅30份、干姜9份、砂仁9份、丁香9份和甘草6份。
3.一种权利要求1所述的缓解酒精性肝损伤的中药组合物的制备方法，其特征在于，包括：对葛根、木瓜、乌梅、干姜、砂仁、丁香和甘草进行处理后混合。
4.根据权利要求3所述的制备方法，其特征在于，包括：对所述葛根、所述木瓜、所述乌梅和所述甘草进行提取形成提取混合物；
将所述砂仁、所述干姜和所述丁香进行粉碎形成粉碎料，而后将所述提取混合物与所述粉碎料混合。
5.根据权利要求4所述的制备方法，其特征在于，将所述葛根、所述木瓜、所述乌梅、所述甘草和水混合后进行煎煮形成煎煮液，而后浓缩形成干膏粉；
将所述砂仁、所述干姜和所述丁香粉碎至粒径小于45μm的超微粉，而后将所述干膏粉与上述超微粉混合。
6.一种中药制剂，其特征在于，其包括权利要求1所述的缓解酒精性肝损伤的中药组合物。
7.根据权利要求6所述的中药制剂，其特征在于，所述中药制剂还包括辅料。
8.根据权利要求6所述的中药制剂，其特征在于，所述中药制剂的剂型包括固体制剂。
9.根据权利要求8所述的中药制剂，其特征在于，固体制剂包括片剂和粉末；优选包括咀嚼片和素片。
10.一种利要求1所述的缓解酒精性肝损伤的中药组合物或权利要求6所述的中药制剂在制备治疗、预防和/或缓解酒精干预所致的肝肠损伤的药物中的应用。
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