第十三期“科创中国”助力产业高质量发展学术研讨会

会议议程

会议时间：2022 年 7 月 30 日 14:30-17:30

会议地点：北京亚洲大酒店（二层锦仁厅）

腾讯会议号 241 402 716

会议主题：七蕊胃舒胶囊创新发展研讨会

会议议程：

时间 内容 发言人 主持人

14:00-14:30 会议签到

14:30-14:40 主持人开场及参会专家介绍 张霄潇

张霄潇

14:40-14:50 中华中医药学会领导致辞 刘 平

14:50-15:10 “科创中国”中医药产业科技服务团项目 郭继华

15:10-15:40 七蕊胃舒胶囊研究进展汇报 黄志军

15:40-17:10 专家发言及讨论 全 体

唐旭东

17:10-17:20 健民集团董事长致谢 何 勤

17:20-17:30 会议总结 唐旭东 张霄潇

参会名单

【中华中医药学会】

刘 平 中华中医药学会副秘书长

张霄潇 中华中医药学会发展研究办公室主任

郭继华 中华中医药学会发展研究办公室

【脾胃病领域研讨专家】

唐旭东 中国中医科学院 副院长

季 光（线上） 上海中医药大学 校长

杨 倩（线上） 河北省中医院 副院长

张声生 首都医科大学附属北京中医医院 消化中心主任

李军祥（线上） 北京中医药大学 消化病研究院院长

刘 力（线上） 陕西省中医药大学 原党委书记

沈 洪（线上） 江苏省中医院 消化科主任

苏娟萍（线上） 山西省中医院 脾胃病科主任

李延萍（线上） 重庆市中医院 主任医师

【交叉学科研讨专家】

张洪春 中日友好医院医疗 保健部主任

赵瑞华 中国中医科学院广安门医院 妇科主任

曹俊岭（线上） 北京中医药大学东直门医院洛阳医院 执行院长

华国栋 北京中医药大学东直门医院 药剂科主任

王丽霞 中国中医科学院广安门医院 药剂科主任

马 勇 首都医科大学国家医疗保障研究院 副研究员

席晓宇（线上） 中国药科大学国家药物政策与医药产业经济研究中心 研究员

【企业参会人员】

何 勤 健民药业集团股份有限公司 董事长

黄志军 健民药业集团股份有限公司 副总裁

健民集团介绍

健民集团，始创于明崇祯十年（1637 年），原名“叶开泰”，解放前便

享有“初清三杰”、“中国四大药号”的美誉，2004 年在上海证券交易所上

市。健民集团以发展中医药为核心，已成为全国重点中药企业，并设有国家

企业技术中心、企业博士后科研工作站和研发中心，具备完善的自主研发能

力。公司为中华老字号企业，拥有“健民”、“龙牡”、“叶开泰”三大品

牌。公司入选“中国最有价值品牌 500 强”，综合实力跻身全国医药企业百

强之列。

健民集团研发中心为湖北省最早的中药研发机构之一，中心拥有一批由

国务院特殊津贴专家、湖北省突出贡献专家、武汉市专家、博士、硕士等各

类人才组成的技术梯队，中、高级专业技术职称人员占 60%以上，主要领导

及学科负责人均具备硕士、博士学历，具有丰富的新药研究开发经验。拥有

2000 多平米实验大楼和 1000 平米中试车间，配备药物制剂、提取、检验、

中试等实验设备百余台套，研发投入达工业收入的 3.5%以上。

健民集团十分重视企业的技术创新工作。1999 年，以集团公司药物研

究所为基础，健民集团联合湖北大学、湖北中医学院、原同济医科大学（药

学院）、武汉市生物技术研究中心等科研院所，组建了武汉市中药现代化工

程技术研究中心，专门从事中药新药、新技术的开发工作。2000 年，该中心

被湖北省科技厅批准为“湖北省中药现代化工程技术研究中心”。公司被认

定为国家高新技术企业，并于 2002 年被国家人事部批准建立“企业博士后

科研工作站”。 研究院在加强内涵建设的基础上，不断丰富“以政府为引

导、以企业为主体、以科研院所为技术依托”的“产、学、研”的合作模式。

中心凝聚了一批国内一流的、以院士为负责人的新药研究及工程化方面的专

家顾问；此外公司还与中科院昆明植物所、北京大学、香港理工大学、华中

科技大学、天津中医药大学、湖北中医药大学等 20 多家国内外科研单位建

立了长期的战略合作关系，丰富和提高了中心的创新能力和创新效率。

产品背景

七蕊胃舒胶囊由健民药业集团股份有限公司自主研发、于 2021 年 12 月

31 日获批生产的 1.1 类中药新药。其功能主治为活血化瘀，燥湿止痛，用于

轻中度慢性非萎缩性胃炎伴糜烂湿热瘀阻证所致的胃脘疼痛，主要优势如下：

一、七蕊胃舒胶囊是“重大新药创制”科技重大专项成果，为首个获批

治疗慢性胃炎的中药 1.1 类新药。

七蕊胃舒胶囊（原名利胃胶囊）源自经典名方“硝石矾石散”、“化血

丹”加减，作为中国中医科学院广安门医院院内制剂应用 30 多年，该项目

被列入了 2018 年度“重大新药创制”科技重大专项，是国内首个获批治疗

慢性胃炎的中药 1.1 类新药，为慢性胃炎的治疗提供了新的治疗选择。

二、七蕊胃舒胶囊是适应我国慢性胃炎疾病变化和治疗的创新药物。

慢性胃炎(CG)是由多种原因引起的胃黏膜的慢性炎症，是消化系统常见

病之一。该病症状易反复发作，严重影响患者的生存质量，如未能及时治疗，

可进一步发展为慢性萎缩性胃炎、胃癌等，已逐渐引起临床重视。

《中国慢性胃炎共识意见(2017 年)》提出，有症状者常见症状为上腹痛

(52.9%)、腹胀(48.7%)，慢性非萎缩性胃炎伴糜烂在各型慢性胃炎中比例为

42.3%，因此治疗胃痛、改善胃黏膜糜烂是慢性胃炎主要的治疗目标，七蕊胃

舒胶囊的临床研究表明，其可以显著止痛，有效修复胃黏膜。

三、七蕊胃舒胶囊是首个明确治疗慢性非萎缩性胃炎伴糜烂的药物。

《中国慢性胃炎共识意见(2017 年)》提出，慢性非萎缩性胃炎伴糜烂在

各型慢性胃炎中比例为 42.3%，该病症发病率高，临床常见。《慢性胃炎中医

诊疗专家共识意见(2017)》将慢性胃炎分为肝胃不和证、脾胃湿热证、脾胃

虚弱证、胃阴不足证、胃络瘀阴证，其中脾胃湿热证、胃络瘀阻证是胃黏膜

糜烂明显、胃痛日久不愈的主要证型。而现有常见药物说明书中尚无明确治

疗慢性非萎缩性胃炎伴糜烂的中成药，1.1 类中药新药七蕊胃舒胶囊是唯一

明确治疗慢性非萎缩性胃炎伴糜烂湿热瘀阻证所致的胃脘疼痛的中成药。

四、七蕊胃舒胶囊的临床研究证实，具有显著止痛、修复胃黏膜的疗效，

是治疗慢性非萎缩性胃炎伴糜烂的有效药物。

上市前的Ⅱ、Ⅲ期临床研究结果证实，七蕊胃舒胶囊对于慢性非萎缩性

胃炎伴湿热瘀阻证发挥了显著的疗效，胃脘疼痛消失率可达 78.9%，胃黏膜

糜烂痊愈率可达 65.3%，中医症候总有效率可达 74.74%。相较阳性药物三九

胃泰、安慰剂，七蕊胃舒胶囊在胃痛消失率、中医证候改善、胃黏膜活动性

炎症等指标显示显著的效果及优势。

综上所述，七蕊胃舒胶囊是首个获批的治疗慢性胃炎的1.1类中药新药，

也是首个明确治疗慢性非萎缩性胃炎伴糜烂湿热瘀阻证所致的胃脘疼痛的

中成药，具有显著止痛、修复胃黏膜的作用。本次会议将对七蕊胃舒胶囊的

创新发展进行探讨，并期望为药品生产企业制定生产发展计划和国家卫生行

政部门制定药物政策提供参考，造福更多慢性胃炎患者！

目录

一、七蕊胃舒胶囊上市历程 .................................................. 1

1、产品基本信息........................................................ 1

2、国家级科创项目成果.................................................. 2

3、产品传承性.......................................................... 2

4、立项目的与依据...................................................... 3

二、七蕊胃舒胶囊药物研究 .................................................. 5

1、组方方解............................................................ 5

2、药理学研究.......................................................... 5

3、药效学研究.......................................................... 6

4、毒理学研究.......................................................... 7

三、七蕊胃舒胶囊临床应用 .................................................. 7

1、临床疗效............................................................ 7

2、临床安全性.......................................................... 9

四、七蕊胃舒胶囊经济性分析 ............................................... 10

1、同类药物对比....................................................... 10

2、增量成本-效果分析.................................................. 11

3、成本-效果分析...................................................... 12

五、 七蕊胃舒胶囊产品总结 ................................................ 13

六、 七蕊胃舒胶囊证明性文件 .............................................. 14

【参考文献】 ............................................................ 15

【附件】 ................................................................ 17

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一、七蕊胃舒胶囊上市历程

1、产品基本信息

【通用名称】七蕊胃舒胶囊

【药品类别】中成药

【成 分】三七、枯矾、煅花蕊石、酒大黄

【性 状】本品为硬胶囊，内容物为浅灰黄色至黄色的粉末；味涩、微苦。

【功能主治】活血化瘀，燥湿止痛。用于轻中度慢性非萎缩性胃炎伴糜烂湿热瘀阻证所

致的胃脘疼痛，舌质紫黯或瘀斑瘀点、舌苔黄腻、脉弦涩或弦滑。

【规 格】每粒装 0.5g（相当于饮片 0.5g）

【用法用量】口服。一次 4 粒，一日 2 次，早晚餐前半小时服用。疗程 4 周。

【不良反应】临床试验期间受试者用药后出现：月经量增多或减少、肝生化指标升高、

腹痛、 腰痛、肠鸣亢进、大便次数增多、便溏、凝血功能异常、皮疹瘙痒、

尿蛋白异常等。

【禁 忌】1.孕妇及哺乳期妇女禁用。

2.正在接受透析治疗者禁用。

3.对本品及所含成份过敏者禁用。

【生产企业】健民药业集团股份有限公司

【批准文号】国药准字 Z20210009

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2、国家级科创项目成果

七蕊胃舒胶囊为 2018 年度“重大新药创制”科技重大专项成果，为中国首个获批治

疗慢性胃炎的 1.1 类创新药，也是首个用于治疗慢性非萎缩性胃炎伴糜烂湿热瘀阻证所

致的胃脘疼痛的中药创新药。（详细内容请见附件）

3、产品传承性

七蕊胃舒胶囊由三七、枯矾、煅花蕊石、酒大黄四味药组成，共奏活血化瘀，燥湿

止痛之功。组方源自经典名方《张锡纯临证用药》“化血丹”、《金匮要略》“硝石矾石散”

加减。

七蕊胃舒胶囊组方作为中国中医科学院广安门医院的院内制剂（批准文号：京药制

Z20063205），由该院消化内科首任主任任俊杰教授研制，已在临床上应用了三十余年。在

作为医院制剂用于临床 30 余年间，其临床疗效与安全性得到了充分验证。结果证明，该

产品治疗慢性胃炎疗效与安全性均很好，服用方便，能满足广大患者的需求。

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4、立项目的与依据

（1）立项目的

消化系统疾病作为常见病、多发病，其发病率占人口总数的约 30%[1]，该类疾病主要

包括慢性非萎缩性胃炎、慢性萎缩性胃炎、急性胃炎、消化道溃疡、功能性消化不良等。

其中慢性非萎缩性胃炎发病率相对最高，其是慢性胃炎患者在接受内镜检查时，内镜下

的一种疾病类型，是胃黏膜在各种致病因素作用下所发生的非萎缩性慢性炎症性病变。

有些慢性非萎缩性胃炎患者还存在伴糜烂的情况，这是指内镜下可见胃黏膜上皮的完整

性受损，但病损不超过粘膜肌层的一种病变[2]。

我国饮食文化多样，随着经济的飞速发展，食品种类丰富，社会压力加大，伴随着人

们饮食习惯、结构的变化，生活方式、节奏的改变，消化系统疾病的发病风险越来越高。

并且随着消化内镜技术的发展及消化内镜检查的普及，临床上慢性胃炎的检出率逐年升

高。有调查显示，我国在接受胃镜检查的患者中，慢性胃炎约占 90%[3]。2014 年，由中华

医学会消化内镜学分会牵头开展的一项横断面调查显示，在各型慢性胃炎中，慢性非萎

缩性胃炎的内镜诊断率约为 49.4%，慢性非萎缩性胃炎伴糜烂的内镜诊断率达 42.3%[4]，

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凌福斌等[5]研究发现，1792 例慢性非萎缩性胃炎伴糜烂的患者中，男女之比为 1.4:1，年

龄≤30 岁的占 5.2%，30～50 岁的占 47.9%，50～70 岁的占 41.5%，≥70 岁的占 5.4%，

表明高发病年龄段为 30～70 岁。张声生[6]等对 960 例慢性非萎缩性胃炎患者进行的一项

流行病学研究发现，伴糜烂者约占 35.7%，可见对于慢性非萎缩性胃炎，糜烂是其高发伴

随状态。胃黏膜糜烂患者较未糜烂患者病程更长，复发率高，并与消化性溃疡、胃出血、

病理炎症程度等均有相关性。本病若不加以诊治，病变不断发展，病情可进一步发展为

慢性萎缩性胃炎、胃溃疡、甚至胃癌等。因此，对于该疾病反复发作者的积极性干预不可

小视。

对于慢性非萎缩性胃炎的治疗，中医学一般从整体出发，采取扶正祛邪的原则辨证

施治，往往具有明显的治疗作用，在一定程度上弥补了现代医学治疗的不足，不仅在缓

解临床症状、延缓病情进展方面颇有优势，而且具有复发率低、副作用少等优点，这表明

中医药在治疗慢性非萎缩性胃炎方面有着巨大的优势。中医认为本病的病因主要有外邪

犯胃、饮食伤胃、情志不畅及脾胃素虚等，均可引起胃失和降而使本病发生。本病的病变

部位在胃，涉及脾，多夹郁热、络瘀、瘀热常合湿浊，虚实夹杂尤为常见，故治疗上应遵

循依证而辨、随证用药的原则，以清热凉血、化瘀散结、化湿袪浊、敛疡生肌等治法，方

能提高临床疗效[7]。

本制剂基于以上分析，从疾病的病因病机出发，科学组方，将中医辨证与现代医学

相结合而开发，并作为医院制剂在临床应用多年，其临床疗效与安全性得到了充分验证。

结果证明，该产品治疗慢性非萎缩性胃炎疗效与安全性均很好，服用方便，能满足广大

患者的需求。为此，本制剂适合开发为中药新药产品，向全社会推广。

（2）立项依据

慢性非萎缩性胃炎的中医辨证分型尚无统一标准。《慢性非萎缩性胃炎中西医结合

诊疗共识意见（2017年）》中，将其分为脾胃湿热证、肝胃不和证、寒热错杂证、脾气

虚证、脾胃虚寒证等证型[8]。《消化系统常见病慢性非萎缩性胃炎中医诊疗指南》中，将

其分为肝胃气滞型、肝胃郁热型、脾胃湿热型、脾胃虚寒型、胃阴不足型、胃络瘀阻型

等证型[9]。由于糜烂性胃炎是一种内生疮疡，遵照《内经》诸痛疮疡，皆属于“火”的

病机，故在辨证的基础上主以清热泻火、生肌敛疮的方法[10]。因此，慢性非萎缩性胃炎

伴糜烂主要由湿热瘀滞导致，其治疗当以化瘀除湿、导滞清热、生肌止痛为法，目的是

去除病因，并缓解症状。本制剂七蕊胃舒胶囊则是针对慢性非萎缩性胃炎伴糜烂湿热瘀

滞者所组方。

5

二、七蕊胃舒胶囊药物研究

1、组方方解

七蕊胃舒胶囊由三七、枯矾、煅花蕊石、酒大黄四味药材组成。方中三七甘缓温通，

苦降下泄，能散瘀止血，消肿定痛，用于瘀血阻滞之胃痛症。《本草纲目》云：“三七止血，

散血，定痛，亦主吐血，衄血，下血”。三七在本方中起主要治疗作用，为方中君药。枯

矾消痰，燥湿，止泻，解毒，杀虫。《本草纲目》云：“吐下痰涎饮癖，燥湿解毒，追涎，

止血定痛，食恶肉，生好肉”。枯矾助三七燥湿生肌、消肿定痛，为臣药。煅花蕊石化瘀

止血，并能制酸止痛，为佐药。《本草纲目》记载煅花蕊石：“治一切失血损伤，其功专于

止血，能使血化为水”。酒大黄味苦、气香、性凉，调气止痛，清上焦血分热毒，引胃气

下行。《卫生宝鉴》卷二十三中记载：“酒煨大黄苦寒，引苦性上行至巅，驱热而下”。可

见，酒大黄能引药上行，驱热下达，清血分热，为方中使药。诸药相合，化瘀除湿，导滞

清热，生肌止痛，用于慢性非萎缩性胃炎伴糜烂湿热瘀滞证，症见胃脘疼痛，胃脘痞胀，

嗳气，纳呆少食，口苦，嘈杂，泛酸等。

2、药理学研究

三七主要成份有三七总皂苷、三七素（三七氨酸）、黄酮、挥发油、氨基酸、糖类等

。药理研究表明，皂苷类成分是三七主要的生理活性成分[11]，其药理作用主要为[12]：活血

作用，三七总皂苷对家兔、大白鼠实验性血栓形成均有明显抑制作用；静脉注射可以明

显抑制凝血所致弥漫性血管内凝血，动物血小板数目的下降和纤维蛋白降解产物的增加

。抗炎镇痛作用，三七总皂苷能明显抑制角叉菜胶诱导的炎细胞增多和蛋白渗出，对急

性炎症引起的毛细血管通透性升高、炎性渗出和组织水肿以及炎症后期肉芽组织增生也

均有抑制作用。此外，三七总皂苷对化学性和热刺激引起的疼痛均有明显的对抗作用，

且三七总皂苷是一种阿片肽样受体刺激剂，但不具有成瘾的副作用。

枯矾为白矾煅制品，具有收湿敛疮、止血化腐的功效。用于湿疹湿疮、脱肛、痔疮、

聤耳流脓、阴痒带下、鼻衄齿衄、鼻瘜肉。另外，枯矾单味或经适当配伍，可治呕吐、泄

泻、胃痛、腹痛、胁痛等证。对现代医学的胆囊炎、胆石症、肠粘连等急腹症及急性胃肠

炎亦有良效[13]。药理研究表明[14]，枯矾的主要药理作用有收敛消炎、抑菌等作用。可从细

胞中吸收水分，使细胞发生脱水缩合，减少腺体分泌，减少炎症渗出物，又可与蛋白质结

合成难溶于水的蛋白化合物而沉淀，使组织或创面呈现干燥，起到收敛燥湿的作用，是

6

中医常用的外用收敛药。而三七具有活血化瘀、去瘀生新的功效。两药合用能共奏祛瘀

燥湿、敛疮生肌之功效，促进伤口愈合。实验证明，枯矾、三七两味中药共同作用能明显

缩短伤口的祛腐生肌时间，抑制细菌、病毒等微生物感染，促进伤口肉芽组织生长，对治

疗伤口溃烂具有明显的优势。

煅花蕊石为花蕊石的炮制品，花蕊石主含碳酸钙（CaCO3），炮制后的煅花蕊石为碳酸

钙及氧化钙的混合物，药理研究表明[15]：煅花蕊石有护膜生肌和络之效，并具有化瘀收

涩止血的作用，易于粉碎，固涩收敛作用增强。此外，因煅花蕊石主含碳酸钙及氧化钙，

可中和胃酸，保护胃黏膜。

酒大黄为大黄的酒炙品，具有泻下攻积，清热泻火，凉血解毒，逐瘀通经，利湿退黄

的功效。善清上焦血分热毒，用于目赤咽肿、齿龈肿痛。主要成分为游离型和结合型蒽醌

类衍生物、鞣质类、二苯乙烯苷类、苯酚苷类和苯丁酮类等。现代药理研究表明[16]，蒽醌

类衍生物及没食子酸等鞣质为大黄收敛、止血作用的主要有效成分。大黄经酒炙后，善

清上焦之火，主要起清胃火，清热导滞、活血化瘀的作用。

以上论述表明，方中三七活血行血；枯矾与煅花蕊石同用，收敛燥湿，促进胃黏膜修

复；酒大黄通腑泻热，解毒活血。诸药配伍使用，对慢性非萎缩性胃炎伴糜烂基本病机中

的“瘀血、热毒、湿热之邪”发挥治疗作用，收敛燥湿，生肌止痛，并能中和胃酸，保护

胃黏膜。结合方解，表明本制剂组方合理，可用于慢性非萎缩性胃炎伴糜烂的治疗。

3、药效学研究

七蕊胃舒胶囊在北京医科大学第三医院开展了药效学研究，各项研究显示其用于慢

性胃炎治疗具有显著的作用机制，具体如下所述：

（1）止痛：通过冰醋酸诱发小鼠腹痛模型研究验证了七蕊胃舒胶囊显著减少小鼠扭体次

数，呈现显著的止痛作用；

（2）改善胃黏膜：显著增加酒精灌胃大鼠胃黏膜血流量，抵抗纯酒精对胃黏膜的损伤，

促进溃疡的愈合，展现出一定的胃黏膜改善作用；

（3）抑制胃酸分泌：显示具有一定的降低总酸排出量的作用，可促进溃疡愈合，轻度抑

制胃酸分泌；

（4）抗幽门螺旋杆菌：通过菌落培养、枸橼酸铋钾阳性对照显示七蕊胃舒胶囊对幽门螺

杆菌生长具有一定的抑制作用。

7

4、毒理学研究

本制剂急性毒性试验及连续给药 11 周的长期毒性试验结果显示，七蕊胃舒胶囊对小

鼠灌胃给药的最大耐受量（MTD）为 32g 生药/kg，相当于临床剂量的 450 倍。给大鼠灌

胃低剂量（1.9g/kg/d）和高剂量（3.8g/kg/d）的利胃胶囊，连续给药 11 周，未见毒性

反应情况，对血常规和血液生化各项指标以及内脏均无影响，表明七蕊胃舒胶囊无明显

毒性作用的最高剂量（NOAEL）为 3.8g/kg/d，相当于临床剂量的 50 倍。由此可见，七蕊

胃舒胶囊具有很好的安全性。

三、七蕊胃舒胶囊临床应用

1、临床疗效

（1）第一次Ⅱ期临床研究

江苏省中医院、山东中医药大学附属医院、湖北中医学院附属医院、山西省中医药

研究院 、陕西省中医药研究院附属医院 5 家中心参与了第一次Ⅱ期临床研究。本试验纳

入符合慢性非萎缩性胃炎伴糜烂的诊断及中医湿热瘀滞证辨证标准的患者 240 例，设七

蕊胃舒胶囊组 120 例、阳性对照组（三九胃泰胶囊组）120 例。两组均为口服药物，服药

方法为：试验组七蕊胃舒胶囊+安慰剂，对照组三九胃泰胶囊+安慰剂，一日 2 次，治疗

周期为 28 天。具体试验结果如下：

①主要疗效指标：

组别 七蕊胃舒胶囊组 三九胃泰组

胃脘疼痛消失率 80.17%

**

57.98%

胃脘痞胀消失率 72.57%

**

45.69%

胃黏膜糜烂有效率 67.89%

*

57.57%

注：与三九胃泰组相比，*

P＜0.05，

**

P＜0.01

②次要疗效指标：

组别 七蕊胃舒胶囊组 三九胃泰组

证候疗效有效率 80.84%

**

52.50%

Hp 改善率 42.2%

△

34.34%

注：与三九胃泰组相比，*

P＜0.05，

**

P＜0.01

8

上述试验结果显示七蕊胃舒胶囊相较于阳性对照药三九胃泰，在胃脘疼痛消失率、

胃脘痞胀消失率、胃黏膜糜烂有效率、证候疗效显效率、HP 根除率等指标方面展现显著

的疗效及优势。

（2）第二次Ⅱ期临床研究[17]

江苏省中医院、甘肃省中医院、河北省中医院、长春中医药大学附属医院、天津中医

药大学第一附属医院 5 家中心参与了第二次Ⅱ期临床研究。本试验纳入符合慢性非萎缩

性胃炎伴糜烂的诊断及中医湿热瘀滞证辨证标准的患者 240 例，设七蕊胃舒胶囊组组 120

例、阳性对照组（三九胃泰胶囊组）与安慰剂对照组各 60 例。三组均为口服药物，每次

4 粒，一日 2 次，治疗周期为 28 天。具体试验结果如下：

①主要疗效指标：

组别 七蕊胃舒胶囊组 三九胃泰组 安慰剂组

胃脘疼痛消失率 78.9%*△

42.2% 28.6%

胃脘痞胀消失率 65.3% 68.9% 53.1%

胃黏膜糜烂有效率 80%*△

55.6% 53.1%

注：与三九胃泰组相比，*

P＜0.05；与安慰剂组相比，△

P＜0.05

②次要疗效指标：

组别 七蕊胃舒胶囊组 三九胃泰组 安慰剂组

证候疗效显效率 74.74%*△

57.78% 30.61%

Hp 根除率 52.7%△

34.6% 22.6%

注：与三九胃泰组相比，*

P＜0.05；与安慰剂组相比，△

P＜0.05

上述试验结果显示七蕊胃舒胶囊相较于阳性对照药三九胃泰、安慰剂，在胃脘疼痛

消失率、胃脘痞胀消失率、胃黏膜糜烂有效率、证候疗效显效率、HP 根除率等指标方面

展现显著的疗效及优势。

（3）Ⅲ期临床研究[18]

由中国人民解放军沈阳军区总医院牵头的 11 家中心参与了Ⅲ期临床研究。本次研究

共纳入符合慢性非萎缩性胃炎伴糜烂的诊断及中医湿热瘀滞证辨证标准的患者标准的

480 例患者，其中七蕊胃舒胶囊组 360 例，三九胃泰胶囊对照组 120 例。两组组均为口服

药物，每次 4 粒，一日 2 次，治疗周期为 28 天。具体试验结果如下：

①主要疗效指标：

9

组别 七蕊胃舒胶囊组 三九胃泰组

上腹痛消失率 64.2%

*

46.7%

轻度上腹痛消失率 65.4 55.2

中度上腹痛消失率 65.0

** 30.4

重度上腹痛消失率 33.3 71.4

注：与三九胃泰组相比，*

P＜0.05，**P＜0.01

②次要疗效指标：

组别 七蕊胃舒胶囊组 三九胃泰组

中医症候总有效率 53.8%

*

38.3%

胃脘痞胀消失率 64.3% 54.5%

胃黏膜糜烂有效率 56.9% 57.5%

活动性炎症痊愈率 52.8% 48.1%

慢性炎症痊愈率 1.00% 0.97%

注：与三九胃泰组相比，*

P＜0.05

上述试验结果显示七蕊胃舒胶囊在研究中展现出了显著的治疗效果，尤其是在缓解

胃脘疼痛及中医证候改善方面效果显著且优于对照药物三九胃泰，并能改善胃镜下胃粘

膜红斑、糜烂表现以及胃脘痞胀、嗳气、纳呆少食、口苦、嘈杂、泛酸等症状。

2、临床安全性

（1）Ⅱ期临床研究[17]

江苏省中医院、甘肃省中医院、河北省中医院、长春中医药大学附属医院、天津中医

药大学第一附属医院 5 家中心参与的Ⅱ期临床研究，统计和分析了纳入研究的 240 例受

试者安全性数据。

七蕊胃舒胶囊组有 3 例（2.5%）发生了与研究药物有关的不良反应，其中 2 例表现

为月经量增多（１例可能与试验用药有关，另１例与试验药物关系为可疑）；１例表现为

肝功能改变（与试验用药关系可疑）；对照组、安慰剂组各有１例发生不良事件（与试验

药物无关）；观察组、对照组及安慰剂组 3 组不良反应差异均无统计学意义（Ｐ＞0.05）。

（2）Ⅲ期临床研究[18]

中国人民解放军沈阳军区总医院牵头的 11 家中心参与的Ⅲ期临床研究，统计和分析

10

了纳入研究的 240 例受试者安全性数据。本试验所发生的不良事件中，经研究者判定 4.23%

（20/473）与试验药物有关。其中七蕊胃舒胶囊组发生 15 例次（14 例，3.94%）不良事

件与试验药有关，对照组发生 6 例次（6 例，5.08%）不良事件与对照药有关。轻度不良

反应试验组为 12 例次（11 例），发生率 3.10%，对照组 5 例次（5 例），发生率 4.24%，

两组间差异无统计学意义（P>0.05）。中度不良反应试验组为 3 次（3 例），对照组 1 例

次，发生率均为 0.85%，两组间差异无统计学意义（P>0.05）。两均未发生严重的不良反

应。本试验试验组 4 例受试者因不良反应而前退出，对照组 1 例前退出。本试验期间发

生了 3 例严重不良事件（SAE），其中 2 例为试验组，1 例为对照组，研究者判定均与试验

药物无关。无死亡事件发生。

（3）说明书相关安全性提示

七蕊胃舒胶囊说明书中不良反应描述为：临床试验期间受试者用药后出现月经量增

多或减少、肝生化指标升高、腹痛、 腰痛、肠鸣亢进、大便次数增多、便溏、凝血功能

异常、皮疹瘙痒、尿蛋白异常等。禁忌描述为：孕妇及哺乳期妇女、正在接受透析治疗

者、对本品及所含成份过敏者禁用。

七蕊胃舒胶囊是最新获批的中药创新药，经历了目前更为严格的中药说明书修订要

求，即对药品的不良反应、禁忌、注意事项以及临床试验安全性数据等有关药物安全性

提示内容进行了详细且明确的描述。这与目前很多同类产品相比，在说明书安全性提示

中均未标注“尚不明确”。因此，七蕊胃舒胶囊在指导安全用药方面具有显著的优势。

四、七蕊胃舒胶囊经济性分析

1、同类药物对比

产品名称 成分

中标价/日

费用（元）

功能主治 用法用量

七蕊胃舒胶囊

三七、枯矾、煅花

蕊石、酒大黄

186.5/62.17

活血化瘀，燥湿止痛。用于轻中度慢性

非萎缩性胃炎伴糜烂湿热瘀阻证所致的

胃脘疼痛，舌质紫黯或瘀斑瘀点、舌苔

黄腻、脉弦涩或弦滑。

口服。一次 4 粒，

一日 2 次，早晚餐

前半小时服用。疗

程 4 周。

益气和胃胶囊

黄芪、丹参、党

参、黄芩、枳壳、

44.79/14.88

健脾和胃，通络止痛。用于慢性非萎缩

性胃炎脾胃虚弱兼胃热瘀阻证，症见胃

口服。一次 4 粒，

一日 3 次。

11

白芍、白术、仙鹤

草、甘草、檀香

脘痞满胀痛、食少纳呆、大便溏薄、体

倦乏力、舌淡苔薄黄、脉细。

三九胃泰胶囊

三叉苦、九里香、

两面针、木香、黄

芩、茯苓、地黄、

白芍

24.46/8.16

清热燥湿，行气活血，柔肝止痛，消炎

止痛，理气健脾。用于上腹隐痛，饱

胀，反酸，恶心，呕吐，纳减，心口嘈

杂。

口服，一次 2～4

粒，一日 2 次。

三九胃泰颗粒

三叉苦、九里香、

两面针、木香、黄

芩、茯苓、地黄、

白芍

16.87/3.38

清热燥湿，行气活血，柔肝止痛。用于

湿热内蕴、气滞血瘀所致的胃痛，症见

脘腹隐痛、饱胀反酸、恶心呕吐、嘈杂

纳减；浅表性胃炎见上述症候者。

用开水冲服，一次 1

袋，一日 2 次。

荜铃胃痛颗粒

荜澄茄、川楝子、

醋延胡索、酒大

黄、黄连、吴茱

萸、醋香附、香

橼、佛手、海螵

蛸、煅瓦楞子

46.6/15.54

行气活血，和胃止痛。用于气滞血瘀所

致的胃脘痛；慢性胃炎见有上述证候

者。

开水冲服。一次 5

克，一日 3 次。

荆花胃康胶丸 土荆芥、水团花 43.09/8.64

理气散寒，清热化瘀。用于寒热错杂

证、气滞血瘀所致的胃脘胀闷疼痛、嗳

气、返酸、嘈杂、口苦；十二指肠溃疡

见上述证候者。

饭前服，一次 2

粒，一日 3 次；4 周

为一疗程，或遵医

嘱。

七蕊胃舒胶囊的同类药物均已纳入医保，但功能主治描述为用于慢性非萎缩性胃炎

的品种仅有一种，七蕊胃舒胶囊也是唯一明确治疗慢性非萎缩性胃炎伴糜烂湿热瘀阻证

所致的胃脘疼痛的中成药，在服用方面一日两次相对较为方便。

2、增量成本-效果分析

根据 2022 年七蕊胃舒胶囊全国主要地区省级药采平台中标价格，得七蕊胃舒胶囊

（24 粒/盒）的最低价格为 186.5 元，即单位剂量价格为 7.77 元/粒；根据 2020-2022 年

益气和胃胶囊全国主要地区省级药采平台中标价格，得益气和胃胶囊（36 粒/盒）的最低

12

价格为 44.79 元，即单位剂量价格为 1.24 元/粒。

基于两种药品的使用说明书，将七蕊胃舒胶囊的用法用量定为 4 粒/次、2 次/天，益

气和胃胶囊的用法用量定为 4 粒/次、3 次/天；以 28 天为一个疗程，计算七蕊胃舒胶囊

及益气和胃胶囊的日均费用、次均费用。

表 1 七蕊胃舒胶囊及益气和胃胶囊治疗慢性非萎缩性胃炎的费用情况（元）

药品 用法用量 单位制剂

最低价格

销售单位

最低价格 日均费用 次均费用

七蕊胃舒胶囊 4 粒*2 次/天 7.77 186.5 62.17 1740.76

益气和胃胶囊 4 粒*3 次/天 1.24 44.79 14.88 416.64

通过中国知网、万方等查阅相关文献，七蕊胃舒胶囊[17]和益气和胃胶囊[19]治疗慢性

非萎缩性胃炎的临床疗效如表 2 所示。

表 2 七蕊胃舒胶囊及益气和胃胶囊治疗慢性非萎缩性胃炎临床疗效

药品 组别 治疗方法 痊愈 显

效

进

步

无

效

恶

化

总有效率

（%）

七蕊胃舒胶囊 对照组 安慰剂 5 10 23 11 30.61

观察组 七蕊胃舒胶囊 26 45 22 2 74.74

益气和胃胶囊

对照组 瑞巴派特片 18 14 6 6 3 68.09

观察组 益气和胃胶囊+瑞巴派

特片 30 11 4 1 1 87.23

注:与对照组比较，P<0.05。

结合七蕊胃舒胶囊和益气和胃胶囊治疗慢性非萎缩性胃炎的临床疗效情况，计算两

者的成本效果发现，当七蕊胃舒胶囊降价 44.63%即 4.30 元/粒以下时，相对益气和胃胶

囊才具有成本效果优势。

表 3 七蕊胃舒胶囊及益气和胃胶囊治疗慢性非萎缩性胃炎的增量成本-效果分析

药品 增量成本 与对照组的疗效差 增量-成本效果比

七蕊胃舒胶囊 1740.67 44.13% 39.45

益气和胃胶囊 418.04 19.14% 21.77

3、成本-效果分析

根据 2022 年七蕊胃舒胶囊全国主要地区省级药采平台中标价格，得七蕊胃舒胶囊

（24 粒/盒）的最低价格为 186.5 元，即单位剂量价格为 7.77 元/粒；根据 2020-2022 年

三九胃泰胶囊全国主要地区省级药采平台中标价格，得三九胃泰胶囊（24 粒/盒）的最低

13

价格为 24.46 元，即单位剂量价格为 1.02 元/粒。

基于两种药品的使用说明书，将七蕊胃舒胶囊的用法用量定为 4 粒/次、2 次/天，三

九胃泰胶囊的用法用量定为 4 粒/次、2 次/天；以 28 天为一个疗程，计算七蕊胃舒胶囊

及三九胃泰胶囊的日均费用、次均费用。

表 1 七蕊胃舒胶囊及三九胃泰胶囊治疗慢性非萎缩性胃炎的费用情况（元）

药品 用法用量 单位制剂

最低价格

销售单位

最低价格 日均费用 次均费用

七蕊胃舒胶囊 4 粒*2 次/天 7.77 186.5 62.17 1740.76

三九胃泰胶囊 4 粒*2 次/天 1.02 24.46 8.16 228.48

通过中国知网、万方等查阅相关文献，七蕊胃舒胶囊和三九胃泰胶囊治疗慢性非萎

缩性胃炎的临床疗效[18]如表 2 所示。结合七蕊胃舒胶囊和三九胃泰胶囊治疗慢性非萎缩

性胃炎的临床疗效情况，计算两者的成本效果发现，当七蕊胃舒胶囊降价 71.96%即 2.17

元/粒以下时，相对三九胃泰胶囊才具有成本效果优势。

表 2 七蕊胃舒胶囊及三九胃泰胶囊治疗慢性非萎缩性胃炎临床疗效

药品 组别 上腹痛消失率 成本-效果 中度上腹痛消失率 成本-效果

七蕊胃舒胶囊 观察组 78.90% 2206.17 65.0% 26.78

三九胃泰胶囊 对照组 42.20% 540.98 30.4% 7.51

注:与对照组比较，P<0.05。

五、七蕊胃舒胶囊产品总结

1、创新性

七蕊胃舒胶囊是国内首个获批治疗慢性胃炎的中药 1.1 类创新药，也是首个明确治

疗慢性非萎缩性胃炎伴糜烂湿热瘀阻证所致的胃脘疼痛的 1.1 类创新药，研究项目被列

入了国家卫生健康委 2018 年度“重大新药创制”科技重大专项，于 2022 年被正式授予

发明专利证书 1 项。

2、传承性

七蕊胃舒胶囊组方源自经典名方“硝石矾石散”、“化血丹”加减，组方为三七、枯

矾、煅花蕊石、酒大黄，共奏活血化瘀，燥湿止痛之效，作为院内制剂（批准文号：京药

制 Z20063205）在中国中医科学院广安门医院应用了三十余年，用于胃痛中医辨证属痰湿

痰滞证患者疗效显著，安全性高。

14

3、有效性

上市前临床研究显示，七蕊胃舒胶囊止痛效果卓越、可显著改善胃胀、嗳气、泛酸等

中医证候，并能显著改善慢性胃炎患者胃黏膜，促进修复。

4、安全性

七蕊胃舒胶囊作为院内制剂已临床使用 30 余年，疗效与安全性均得到了充分验证。

同时，产品说明书中对不良反应、禁忌、注意事项均进行了详细且明确的描述，相较同类

药品的用药指导更加规范，用药更安全。

5、经济性

通过比较功效、适应症等，选用益气和胃胶囊作为参照药物时，当七蕊胃舒胶囊价

格为 4.30 元/粒以下，可具有更好的成本效果优势。

6、公平性

七蕊胃舒胶囊是首个明确治疗慢性非萎缩性胃炎伴糜烂湿热瘀阻证所致的胃脘疼痛

的中药创新药，可填补该病证的药物空白，功能主治和临床适用患者明确，用法用量清

晰，不易形成临床滥用现象，临床管理难度低。

六、七蕊胃舒胶囊证明材料（附后）

1、七蕊胃舒胶囊说明书

2、七蕊胃舒胶囊 1.1 类新药注册批件

3、七蕊胃舒胶囊临床伦理批件

4、国家科技重大专项“重大新药创制”项目

5、七蕊胃舒胶囊发明专利证书

6、七蕊胃舒胶囊Ⅱ 、Ⅲ 期临床研究结果

7、益气和胃胶囊对照文献

15

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感染、黏膜糜烂的关系研究[J]. 中国中医药信息杂志, 2007,17(4):25-26.

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2006,25(10):666-667.

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中医杂志, 2019,34(8):3613-3618.

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2015:17.

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236.

[15]巩江, 付玲, 白晗. 花蕊石的药学研究概况[J]. 宁夏农林科技, 2013,54(7):75-77.

[16]祝婷婷, 刘晓, 汪小莉. 大黄不同方法炮制后药理作用及化学成分变化研究进展[J]. 中国

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新药杂志, 2016,25(8):883-887.

[17]韩树堂,陈静,田旭东,刘启泉,刘铁军,周正华.七蕊胃舒胶囊对慢性浅表性胃炎伴糜烂湿热

瘀滞证随机、双盲、多中心平行对照临床试验[J/OL].世界中医药:1-5[2022-06-29].

[18]Chen.et al.Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule

in treating chronic non-atrophic gastritis: A multicentre,double-blind,randomized

controlled clinical trial.Journal of Ethnopharmacology294(2022)115341.

[19]覃辉、何礼安等.益气和胃胶囊联合瑞巴派特治疗慢性非萎缩性胃炎的临床研究.现代药物与

临床, 2019.8.

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基金项目：国家科技重大专项（２０１８ＺＸ０９７３１００４）

作者简介：韩树堂 （１９６３０１—２０２１０７），男，博士，主任医师，研究方向：消化系统疾病中西医临床研究，Ｅｍａｉｌ：ｈｓｔｊｓｓｚｙｙ＠ｓｉｎａｃｏｍ

七蕊胃舒胶囊对慢性浅表性胃炎伴糜烂湿热瘀滞证

随机、双盲、多中心平行对照临床试验

韩树堂 １

陈 静１ 田旭东２ 刘启泉３ 刘铁军４ 周正华５

（１江苏省中医院脾胃病科，南京，２１０００４；２甘肃省中医院脾胃病科，兰州，７３００５０；３河北省中医院脾胃病科，石家庄，０５００１３；

４长春中医药大学附属医院肝脾胃科，长春，１３００２１；５天津中医药大学附属医院脾胃科，天津，３００１９２）

摘要 目的：评价七蕊胃舒胶囊治疗慢性浅表性胃炎伴糜烂湿热瘀滞证的有效性和安全性。方法：选取 ２０１２年 １０月至

２０１５年 ３月江苏省中医院、甘肃省中医院、河北省中医院、长春中医药大学附属医院、天津中医药大学附属医院等 ５家中

心收治的慢性浅表性胃炎伴糜烂湿热瘀滞证患者 ２３１例作为研究对象。随机分为观察组、对照组及安慰剂组。观察组口

服七蕊胃舒胶囊，对照组患者口服三九胃泰胶囊，安慰剂组患者口服安慰剂，３组均为 ４粒／次，２次／ｄ，餐前半小时服用，

疗程 ２８ｄ。观察用药后各项症状的改变情况和不良反应。结果：观察组胃脘疼痛消失率高于对照组及安慰剂组，差异有

统计学意义（Ｐ＜００５）；观察组胃黏膜糜烂痊愈率显著高于对照组及安慰剂组，差异有统计学意义（Ｐ＜００５）；观察组证

候疗效的痊愈率及总显效率显著高于对照组及安慰剂组，差异有统计学意义（Ｐ＜００５）；观察组幽门螺杆菌根除率高于

对照组及安慰剂组，其中，观察组与安慰剂组根除率差异有统计学意义（Ｐ＜００１），而与对照组差异无统计学意义（Ｐ＞

００５）；观察组不良反应发生率为 ２６％，对照组无不良反应记录，安慰剂组不良反应发生率为 １８％，３组差异无统计学意

义（Ｐ＞００５）。结论：七蕊胃舒胶囊在治疗慢性浅表性胃炎伴糜烂湿热瘀滞证方面临床疗效显著，安全性较好。

关键词 七蕊胃舒胶囊；慢性浅表性胃炎；糜烂；湿热瘀滞；随机；双盲；多中心

ＥｆｆｅｃｔｏｆＱｉｒｕｉＷｅｉｓｈｕＣａｐｓｕｌｅｓｏｎＣｈｒｏｎｉｃＳｕｐｅｒｆｉｃｉａｌＧａｓｔｒｉｔｉｓｗｉｔｈＥｒｏｓｉｏｎａｎｄＤａｍｐｎｅｓｓＨｅａｔＳｔａｓｉｓＳｙｎｄｒｏｍｅ：

ＡＲａｎｄｏｍｉｚｅｄ，ＤｏｕｂｌｅＢｌｉｎｄｅｄ，ＰｌａｃｅｂｏＣｏｎｔｒｏｌｌｅｄＰａｒａｌｌｅｌＭｕｌｔｉＣｅｎｔｅｒＴｒｉａｌ

ＨＡＮＳｈｕｔａｎｇ１

，ＣＨＥＮＪｉｎｇ１

，ＴＩＡＮＸｕｄｏｎｇ２

，ＬＩＵＱｉｑｕａｎ３

，ＬＩＵＴｉｅｊｕｎ４

，ＺＨＯＵＺｈｅｎｇｈｕａ５

（１ＤｅｐａｒｔｍｅｎｔｏｆＳｐｌｅｅｎａｎｄＳｔｏｍａｃｈＤｉｓｅａｓｅｓ，ＪｉａｎｇｓｕＰｒｏｖｉｎｃｅＨｏｓｐｉｔａｌｏｆＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，Ｎａｎｊｉｎｇ２１０００４，Ｃｈｉｎａ；

２ＤｅｐａｒｔｍｅｎｔｏｆＳｐｌｅｅｎａｎｄＳｔｏｍａｃｈＤｉｓｅａｓｅｓ，ＧａｎｓｕＰｒｏｖｉｎｃｉａｌＨｏｓｐｉｔａｌｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，Ｌａｎｚｈｏｕ

７３００５０，Ｃｈｉｎａ；３ＤｅｐａｒｔｍｅｎｔｏｆＳｐｌｅｅｎａｎｄＳｔｏｍａｃｈＤｉｓｅａｓｅｓ，ＨｅｂｅｉＰｒｏｖｉｎｃｉａｌＨｏｓｐｉｔａｌｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅ

Ｍｅｄｉｃｉｎｅ，Ｓｈｉｊｉａｚｈｕａｎｇ０５００１３，Ｃｈｉｎａ；４ＡｆｆｉｌｉａｔｅｄＨｏｓｐｉｔａｌｏｆＣｈａｎｇｃｈｕｎＵｎｉｖｅｒｓｉｔｙｏｆＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，

Ｃｈａｎｇｃｈｕｎ１３００２１，Ｃｈｉｎａ；５ＤｅｐａｒｔｍｅｎｔｏｆＳｐｌｅｅｎａｎｄＳｔｏｍａｃｈＤｉｓｅａｓｅｓ，ＡｆｆｉｌｉａｔｅｄＨｏｓｐｉｔａｌｏｆＴｉａｎｊｉｎ

ＵｎｉｖｅｒｓｉｔｙｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，Ｔｉａｎｊｉｎ３００１９２，Ｃｈｉｎａ）

Ａｂｓｔｒａｃｔ Ｏｂｊｅｃｔｉｖｅ：ＴｏｅｖａｌｕａｔｅｔｈｅｅｆｆｉｃａｃｙａｎｄｓａｆｅｔｙｏｆＱｉｒｕｉＷｅｉｓｈｕＣａｐｓｕｌｅｓｉｎｔｈｅｔｒｅａｔｍｅｎｔｏｆｃｈｒｏｎｉｃｓｕｐｅｒｆｉｃｉａｌｇａｓｔｒｉｔｉｓ

ｗｉｔｈｅｒｏｓｉｏｎａｎｄｄａｍｐｎｅｓｓｈｅａｔｓｔａｓｉｓｓｙｎｄｒｏｍｅ．Ｍｅｔｈｏｄｓ：Ａｔｏｔａｌｏｆ２３１ｐａｔｉｅｎｔｓｗｉｔｈｃｈｒｏｎｉｃｓｕｐｅｒｆｉｃｉａｌｇａｓｔｒｉｔｉｓｗｉｔｈｅｒｏｓｉｏｎａｎｄ

ｄａｍｐｎｅｓｓｈｅａｔｓｔａｓｉｓｓｙｎｄｒｏｍｅｔｒｅａｔｅｄｉｎｔｈｅＪｉａｎｇｓｕＰｒｏｖｉｎｃｅＨｏｓｐｉｔａｌｏｆＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，ＧａｎｓｕＰｒｏｖｉｎｃｉａｌＨｏｓｐｉｔａｌｏｆＴｒａｄｉ

ｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，ＨｅｂｅｉＰｒｏｖｉｎｃｉａｌＨｏｓｐｉｔａｌｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，ＡｆｆｉｌｉａｔｅｄＨｏｓｐｉｔａｌｏｆＣｈａｎｇｃｈｕｎＵｎｉｖｅｒｓｉｔｙｏｆ

ＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ，ａｎｄＡｆｆｉｌｉａｔｅｄＨｏｓｐｉｔａｌｏｆＴｉａｎｊｉｎＵｎｉｖｅｒｓｉｔｙｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅｆｒｏｍＯｃｔｏｂｅｒ２０１２ｔｏＭａｒｃｈ２０１５

ｗｅｒｅｅｎｒｏｌｌｅｄａｎｄｒａｎｄｏｍｌｙｄｉｖｉｄｅｄｉｎｔｏａｎｏｂｓｅｒｖａｔｉｏｎｇｒｏｕｐ（ＱｉｒｕｉＷｅｉｓｈｕＣａｐｓｕｌｅｓ），ａｃｏｎｔｒｏｌｇｒｏｕｐ（ＳａｎｊｉｕＷｅｉｔａｉＣａｐｓｕｌｅｓ），

ａｎｄａｐｌａｃｅｂｏｇｒｏｕｐ（ｐｌａｃｅｂｏ）．Ａｌｌｐａｔｉｅｎｔｓｗｅｒｅｔｒｅａｔｅｄｃｏｒｒｅｓｐｏｎｄｉｎｇｌｙ３０ｍｉｎｂｅｆｏｒｅｍｅａｌｓ，４ｃａｐｓｕｌｅｓｅａｃｈｔｉｍｅ，ｔｗｏｔｉｍｅｓａ

ｄａｙｆｏｒ２８ｄａｙｓ．Ｔｈｅｃｈａｎｇｅｓｉｎｓｙｍｐｔｏｍｓａｎｄａｄｖｅｒｓｅｒｅａｃｔｉｏｎｓａｆｔｅｒｔｒｅａｔｍｅｎｔｗｅｒｅｏｂｓｅｒｖｅｄ．Ｒｅｓｕｌｔｓ：Ｔｈｅｄｉｓａｐｐｅａｒａｎｃｅｒａｔｅｏｆ

ｅｐｉｇａｓｔｒｉｃｐａｉｎｉｎｔｈｅｏｂｓｅｒｖａｔｉｏｎｇｒｏｕｐｗａｓｈｉｇｈｅｒｔｈａｎｔｈｏｓｅｉｎｔｈｅｃｏｎｔｒｏｌｇｒｏｕｐａｎｄｔｈｅｐｌａｃｅｂｏｇｒｏｕｐ（Ｐ＜００５）．Ｔｈｅｒｅｃｏｖｅｒｙ

ｒａｔｅｏｆｇａｓｔｒｉｃｍｕｃｏｓａｌｅｒｏｓｉｏｎｉｎｔｈｅｏｂｓｅｒｖａｔｉｏｎｇｒｏｕｐｗａｓｈｉｇｈｅｒｔｈａｎｔｈｏｓｅｉｎｔｈｅｃｏｎｔｒｏｌｇｒｏｕｐａｎｄｔｈｅｐｌａｃｅｂｏｇｒｏｕｐ（Ｐ＜

００５）．Ｔｈｅｃｕｒｅｒａｔｅａｎｄｔｏｔａｌｅｆｆｅｃｔｉｖｅｒａｔｅｉｎｔｈｅｅｘｐｅｒｉｍｅｎｔａｌｇｒｏｕｐｗｅｒｅｈｉｇｈｅｒｔｈａｎｔｈｏｓｅｉｎｔｈｅｃｏｎｔｒｏｌｇｒｏｕｐａｎｄｔｈｅｐｌａｃｅｂｏ

ｇｒｏｕｐ（Ｐ＜００５）．ＴｈｅｅｒａｄｉｃａｔｉｏｎｒａｔｅｏｆＨｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉｉｎｔｈｅｏｂｓｅｒｖａｔｉｏｎｇｒｏｕｐｗａｓｈｉｇｈｅｒｔｈａｎｔｈｏｓｅｉｎｔｈｅｃｏｎｔｒｏｌｇｒｏｕｐ

ａｎｄｔｈｅｐｌａｃｅｂｏｇｒｏｕｐ，ａｎｄｔｈｅｄｉｆｆｅｒｅｎｃｅｉｎｔｈｅｅｒａｄｉｃａｔｉｏｎｒａｔｅｂｅｔｗｅｅｎｔｈｅｏｂｓｅｒｖａｔｉｏｎｇｒｏｕｐａｎｄｔｈｅｐｌａｃｅｂｏｇｒｏｕｐｗａｓｓｔａｔｉｓｔｉ

ｃａｌｌｙｓｉｇｎｉｆｉｃａｎｔ（Ｐ＜００１），ｂｕｔｔｈｅｒｅｗａｓｎｏｓｔａｔｉｓｔｉｃａｌｄｉｆｆｅｒｅｎｃｅｂｅｔｗｅｅｎｔｈｅｏｂｓｅｒｖａｔｉｏｎｇｒｏｕｐａｎｄｔｈｅｃｏｎｔｒｏｌｇｒｏｕｐ（Ｐ＞００５）．

Ｔｈｅｉｎｃｉｄｅｎｃｅｏｆａｄｖｅｒｓｅｒｅａｃｔｉｏｎｓｉｎｔｈｅｏｂｓｅｒｖａｔｉｏｎｇｒｏｕｐｗａｓ２６％，ｗｈｉｌｅｎｏａｄｖｅｒｓｅｒｅａｃｔｉｏｎｓｗｅｒｅｒｅｃｏｒｄｅｄｉｎｔｈｅｃｏｎｔｒｏｌ

ｇｒｏｕｐ，ａｎｄｔｈｅｉｎｃｉｄｅｎｃｅｏｆａｄｖｅｒｓｅｒｅａｃｔｉｏｎｓｉｎｔｈｅｐｌａｃｅｂｏｇｒｏｕｐｗａｓ１８％，ｗｉｔｈｎｏｓｉｇｎｉｆｉｃａｎｔｄｉｆｆｅｒｅｎｃｅｂｅｔｗｅｅｎｔｈｅｔｈｒｅｅ

ｇｒｏｕｐｓ（Ｐ＞００５）．Ｃｏｎｃｌｕｓｉｏｎ：ＱｉｒｕｉＷｅｉｓｈｕＣａｐｓｕｌｅｓｓｈｏｗｓｉｇｎｉｆｉｃａｎｔｃｌｉｎｉｃａｌｅｆｆｉｃａｃｙａｎｄｇｏｏｄｓａｆｅｔｙｉｎｔｈｅｔｒｅａｔｍｅｎｔｏｆｃｈｒｏｎｉｃ

ｓｕｐｅｒｆｉｃｉａｌｇａｓｔｒｉｔｉｓｗｉｔｈｅｒｏｓｉｏｎａｎｄｄａｍｐｎｅｓｓｈｅａｔｓｔａｓｉｓｓｙｎｄｒｏｍｅ．

Ｋｅｙｗｏｒｄｓ　ＱｉｒｕｉＷｅｉｓｈｕＣａｐｓｕｌｅｓ；Ｃｈｒｏｎｉｃｓｕｐｅｒｆｉｃｉａｌｇａｓｔｒｉｔｉｓ；Ｅｒｏｓｉｏｎ；Ｄａｍｐｎｅｓｓｈｅａｔｓｔａｓｉｓ；Ｒａｎｄｏｍｉｚｅｄ；Ｄｏｕｂｌｅｂｌｉｎｄｅｄ；

世界中医药　２０２２年 ５月第 １７卷第 １０期 · ５３４１ ·网络首发时间：2022-05-30 16:56:41

网络首发地址：https://kns.cnki.net/kcms/detail/11.5529.R.20220527.1537.012.html

Ｍｕｌｔｉｃｅｎｔｅｒ

中图分类号：Ｒ２４２；Ｒ５７３３＋１ 文献标识码：Ａ ｄｏｉ：１０．３９６９／ｊ．ｉｓｓｎ．１６７３－７２０２．２０２２．１０．０１５

　　慢性浅表性胃炎是由幽门螺杆菌感染、炎症细

胞浸润、十二指肠胃反流或药物毒理反应介导的一

系列的胃黏膜慢性炎症改变，是以腹部胀满、反酸嗳

气、食欲不振等为主要表现的消化系统疾病［１］

。慢

性浅表性胃炎病因复杂、病程较长，临床难以彻底治

愈，如未获得有效治疗可发展为慢性萎缩性胃炎，甚

至少数患者还存在癌变风险［２］

。目前西医对其治疗

多依靠抑制胃酸分泌、保护胃黏膜、促胃动力等进行

治疗，存在周期长、费用高、疗效不理想等缺点［３］

。研

究表明，我国人口基数大，为慢性胃炎大国，在治疗该

病过程中，中医学发挥着积极作用［４］

。中医根据慢性

浅表性胃炎临床症状，将其归属于“胃脘痛”“痞满”

“纳呆”等范畴，认为慢性浅表性胃炎多是由于饮食不

节，过食肥甘厚腻，饮酒，情志不畅等因素导致脾胃失

和，脾失健运，胃失和降，食滞胃脘、气滞血瘀、湿热内

阻等而产生腹胀、反酸、嗳气、恶心等症状［５］

。

七蕊胃舒胶囊由三七、酒大黄、枯矾和煅花蕊石

４味药组成，具有化瘀除湿、导滞清热、生肌止痛等

功效。前期实验研究表明，七蕊胃舒胶囊具有保护

胃黏膜损伤、抑制幽门螺杆菌生长的作用，对慢性浅

表性胃炎伴糜烂湿热瘀滞证具有较好的治疗效果，

并且七蕊胃舒胶囊为中医药制剂，具有不良反应少，

安全性高等优势。基于此，本研究拟采用随机、双盲、

平行对照、多中心临床试验方法观察七蕊胃舒胶囊治

疗慢性浅表性胃炎伴糜烂湿热瘀滞证的临床疗效及

安全性，旨在为该药的临床应用及推广提供依据。

１　资料与方法

１１　一般资料 选取 ２０１２年 １０月至 ２０１５年 ３月

江苏省中医院、甘肃省中医院、河北省中医院、长春

中医药大学附属医院、天津中医药大学附属医院等

５家中心收治的慢性浅表性胃炎伴糜烂湿热瘀滞证

患者 ２３１例作为研究对象。采用随机、双盲、平行对

照、多中心临床试验方法，利用 ＳＡＳ９２统计软件包

进行随机编码数字分配，将各中心收治的慢性浅表

性胃炎伴糜烂湿热瘀滞证患者分为观察组、对照组

及安慰剂组，３组之间的随机比例为 ２∶１∶１。共有

２３１例进入全分析集（ＦｕｌｌＡｎａｌｙｓｉｓＳｅｔ，ＦＡＳ）（观察

组 １１６例、对照组 ５８例、安慰剂组 ５７例）、１８９例进

入符合方案集（ＰｅｒＰｒｏｔｏｃｏｌＳｅｔ，ＰＰＳ）（观察组 ９５例、

对照组 ４５例、安慰剂组 ４９例）、２３１例进入安全数

据集（ＳａｆｅｔｙＳｅｔ，ＳＳ）（观察组 １１６例、对照组 ５８例、

安慰剂组 ５７例）。观察组中男 ３３例，女 ６２例，平均

年龄（４２９９±１３７２）岁，平均病程（１５１２±２４５６）

月；安 慰 剂 组 中 男 ２０例，女 ２９例，平 均 年 龄

（４４９２±１１９９）岁，平均病程（２４３１±３９３９）月；

对照组中男 ２１例，女 ２４例，平均年龄 （４４００±

１４０２）岁，平均病程（１２９２±１５６９）月。ＰＰＳ显示，

３组在年龄、性别、病程、合并疾病、胃脘疼痛、胃脘

痞胀、胃底（糜烂灶）、胃角（糜烂灶）、胃窦（糜烂

灶）、胃底（出血点／斑）、胃体（出血点／斑）、胃角（出

血点／斑）、胃窦（出血点／斑）、嗳气、尿素酶快速试

验检测幽门螺杆菌、纳呆少食、口苦或口臭或黏、嘈

杂、泛酸症状上经统计学分析，差异无统计学意义

（Ｐ＞００５），具有可比性。本临床试验经医院伦理

委员会批准并与患者签署知情同意书（伦理审批号：

２０１１ＮＬ０４１０４）。

１２　诊断标准

１２１　慢性浅表性胃炎伴糜烂西医诊断标准 参

考中华医学会消化学分会 ２０００年江西井冈山《全国

慢性胃炎研讨会共识意见》《中药新药临床研究指

导原则》制定西医诊断标准。１）症状：病程迁延；有

不同程度消化不良、厌食及与进食有关的上腹部疼

痛；可伴有左上腹部轻度压痛。２）符合慢性浅表性

胃炎伴糜烂内镜诊断标准及病理组织学诊断标准即

可确诊。

１２２　慢性浅表性胃炎伴糜烂湿热瘀滞证中医辨

证标准 依据 １９９５国家中医药管理局《中华人民共

和国中医药行业标准·中医病症诊断疗效标准》

《中药新药临床研究指导原则》“中药新药治疗慢性

浅表性胃炎伴糜烂的临床研究指导原则”“中药新

药治疗胃脘痛的临床研究指导原则”的标准，中国中

医药学会中医诊断专业委员会《中医病证治法术

语》（１９９７年），中国中医药学会脾胃病专业委员会

《实用中医消化病学》。主症：１）胃脘疼痛；２）胃脘

痞胀。次症：１）口苦、口臭或口黏；２）纳呆少食；３）

嗳气；４）嘈杂；５）泛酸；６）舌质紫暗或有瘀斑瘀点；

舌脉：苔黄腻；脉弦涩或弦滑。具备主症 １项，次症 ２

项和相应舌脉即可诊断。

１３　纳入标准　１）符合慢性浅表性胃炎伴糜烂的

西医诊断标准；２）符合中医湿热瘀滞证辨证标准；３）

年龄在 １８～６５岁者，性别不限；４）知情同意，志愿受

试。获得知情同意书过程应符合药品临床试验管理

· ６３４１ · ＷＯＲＬＤＣＨＩＮＥＳＥＭＥＤＩＣＩＮＥ　Ｍａｙ．２０２２，Ｖｏｌ．１７，Ｎｏ．１０

规范规定。

１４　排除标准　１）慢性萎缩性胃炎；其他继发性胃

炎；合并有胃、十二肠溃疡，胃黏膜有重度异型增生

或病理诊断疑有恶变者；２）本次发病后 １周内已使

用相关治疗药物；３）妊娠期、哺乳期妇女；４）具有严

重的原发性心、肝、肺、肾、血液或影响其生存的严重

疾病，如肿瘤或艾滋病；肾功能异常；谷丙转氨酶

（ＧｌｕｔａｍｉｃｐｙｒｕｖｉｃＴｒａｎｓａｍｉｎａｓｅ，ＧＰＴ）＞２Ｎ（Ｎ为正

常值上限）；血白细胞 ＜３０×１０９／Ｌ；５）由于精神和

行为障碍不能给予充分知情同意者；６）怀疑或确有

乙醇、药物滥用病史；７）根据研究者的判断，具有降

低入组可能性或使入组复杂化的其他病变，如工作

环境经常变动等易造成失访的情况；８）过敏体质，如

对 ２种或以上药物或食物过敏史者；或已知对本药

成分过敏者；９）正在参加其他药物临床试验的患者。

１５　脱落与剔除标准 未完成本方案所规定的疗

程及观察周期。资料统计分析前，由统计人员及主

要研究者讨论判断病例是否剔除。

１６　治疗方法 按每位受试者入组先后顺序和药

物编号顺序逐例发药。观察组予以七蕊胃舒胶囊

（武汉健民药业集团股份有限公司，批号：１２０５０１）口

服，４粒／次，２次／ｄ，连续服药 ４周。观察组予以三

九胃泰胶囊（华润三九医药股份有限公司，批号：

１２０１００５Ｈ）口服，４粒／次，２次／ｄ，连续服药 ４周。

安慰剂组予以安慰剂（外观与七蕊胃舒胶囊、三九胃

泰胶囊一致，符合安慰剂制备要求，武汉健民药业集

团股份有限公司，批号：１３０７０１）口服，４粒／次，２次／

ｄ，连续服药 ４周。

１７　观察指标　１）胃脘疼痛、胃脘痞胀消失率。２）

胃黏膜糜烂改善情况，胃镜检查，痊愈：糜烂消失，显

效：糜烂分级由 ３级降为 １级，有效：糜烂分级降低 １

个等级，即由 ３级降为 ２级或由 ２级降为 １级，无

效：糜烂无好转，甚或加重。３）纳呆少食、口苦或口

臭或黏、嘈杂、泛酸证候疗效。４）幽门螺杆菌根除

率，根除：治疗后幽门螺杆菌 Ｃ１３或 Ｃ１４检测由阳性

转为阴性；未根除：治疗后幽门螺杆菌 Ｃ１３或 Ｃ１４检

测仍为阳性。５）记录不良反应。

１８　疗效判定标准 疗效采用尼莫地平法计算，公

式为 ＝（疗前证候积分 －疗后证候积分）／疗前证候

积分。临床痊愈：症状、体征消失或基本消失，疗效

指数≥９５％。显效：症状、体征明显改善，７０％≤疗

效指数 ＜９５％。有效：症状、体征好转，３０％≤疗效

指数 ＜７０％。无效：症状、体征无明显改善，甚或加

重，疗效指数 ＜３０％。“临床痊愈、显效”合并计算总

有效率。

１9 统计学方法 采用 ＳＡＳ９２统计软件进行数据

分析。除优效性检验的统计检验均采用双侧检验，

Ｐ≤００５者将被认为所检验的判别有统计学意义。

对胃脘疼痛、胃脘痞胀消失率及幽门螺杆菌根除率

采用 χ

２检验；对胃镜下胃黏膜糜烂总体疗效、中医

证候疗效采用 χ

２ 检验。对不良事件采用 χ

２ 检验／

Ｆｉｓｈｅｒ法检验。

２　结果

２１　各组患者治疗后胃脘疼痛消失率比较 观察

组胃脘疼痛消失率最高，安慰剂组的消失率最低，３

组消失率分别为 ７８９％、４２２％、２８６％；观察组胃

脘疼痛消失率显著高于对照组及安慰剂组，且差异

有统计学意义（Ｐ＜００５）；对照组胃脘疼痛消失率

虽高于安慰剂组，但差异无统计学意义（Ｐ＞００５）。

见表 １。

表 １　各组患者胃脘疼痛消失率比较［例（％）］

组别 消失 未消失

观察组（ｎ＝９５） ７５（７８９）△ ２０（２１１）

对照组（ｎ＝４５） １９（４２２） ２６（５７８）

安慰剂组（ｎ＝４９） １４（２８６） ３５（７１４）

　　注：与对照组比较， Ｐ＜００５；与安慰剂组比较，△ Ｐ＜００５

２２　各组患者治疗后胃脘痞胀消失率比较 观察

组胃 脘 痞 胀 消 失 率 （６５３％）略 低 于 对 照 组

（６８９％），差异无统计学意义（Ｐ＞００５）；安慰剂组

胃脘痞胀消失率最低，为 ５３１％，与其他 ２组之间的

差异同样无统计学意义（Ｐ＞００５）。见表 ２。

表 ２　各组患者胃脘痞胀消失率比较［例（％）］

组别 消失 未消失

观察组（ｎ＝９５） ６２（６５３） ３３（３４７）

对照组（ｎ＝４５） ３１（６８９） １４（３１１）

安慰剂组（ｎ＝４９） ２６（５３１） ２３（４６９）

２３　各组患者治疗后胃黏膜糜烂疗效比较 观察

组胃黏膜糜烂痊愈率最高，安慰剂组的痊愈率最低，

３组痊愈率分别为 ６５３％、４６７％、３０６％；观察组

胃黏膜糜烂痊愈率显著高于对照组及安慰剂组，且

差异有统计学意义（Ｐ＜００５）；对照组胃黏膜糜烂

痊愈率虽高于安慰剂组，但差异无统计学意义（Ｐ＞

００５）。见表 ３。

表 ３　各组患者胃黏膜糜烂疗效比较［例（％）］

组别 痊愈 显效 进步 无效

观察组（ｎ＝９５） ６２（６５３）△ １（１１） １３（１３７） １９（２００）

对照组（ｎ＝４５） ２１（４６７） １（２２） ３（６７） ２０（４４４）

安慰剂组（ｎ＝４９）１５（３０６） ０（００） １１（２２４） ２３（４６９）

　　注：与对照组比较， Ｐ＜００５；与安慰剂组比较，△ Ｐ＜００５

世界中医药　２０２２年 ５月第 １７卷第 １０期 · ７３４１ ·

表 ４　各组患者证候疗效分析

组别 痊愈［例（％）］ 显效［例（％）］ 进步［例（％）］ 无效［例（％）］ 有效率（％）

观察组（ｎ＝９５） ２６（２７３７）△△ ４５（４７３７） ２２（２３１６） ２（２１１） ７４７４

对照组（ｎ＝４５） ６（１３３３） ２０（４４４４） １３（２８８９） ６（１３３３） ５７７８

安慰剂组（ｎ＝４９） ５（１０２０） １０（２０４１） ２３（４６９４） １１（２２４５） ３０６１

　　注：与对照组比较， Ｐ＜００５；与安慰剂组比较，△ Ｐ＜００５， Ｐ＜００１

２４　各组患者治疗后证候疗效比较 观察组证候

疗效的痊愈率最高，为 ２７３７％显著高于对照组及

安慰剂组，且差异有统计学意义（Ｐ＜００５）；对照组

证候疗效的治愈率高于安慰剂组，但差异无统计学

意义（Ｐ＞００５）；观察组有效率显著高于对照组及

安慰组，差异有统计学意义（Ｐ＜００５），同时，对照

组有效率也高于安慰剂组，差异有统计学意义（Ｐ＜

００１）。见表 ４。

２５　各组患者治疗后幽门螺杆菌根除率比较 观

察组幽门螺杆菌根除率为 ５２７％，高于对照组及安

慰剂组，其中，观察组与安慰剂组间根除率差异有统

计学意义（Ｐ＜００１），而观察组幽门螺杆菌根除率

虽高于对照组，但差异无统计学意义（Ｐ＞００５）；同

时，对照组幽门螺杆菌根除率也高于安慰剂组，但差

异也无统计学意义（Ｐ＞００５）。见表 ５。

表 ５　各组患者幽门螺杆菌根除率比较［例（％）］

组别 根除 未根除 合计（缺失）

观察组（ｎ＝９５） ２９（５２７） ２６（４７３） ５５（４０）

对照组（ｎ＝４５） ９（３４６） １７（６５４） ２６（１９）

安慰剂组（ｎ＝４９） ７（２２６） ２４（７７４） ３１（１８）

　　注：与安慰剂组比较， Ｐ＜００１

２６　各组不良事件比较 观察组有 ３例发生了与

研究药物有关的不良反应，其中 ２例表现为月经量

增多（１例可能与试验用药有关，另 １例与试验药物

关系为可疑）；１例表现为肝功能改变（与试验用药

关系可疑）；安慰剂组有 １例发生不良事件（与试验

药不可能有关系）；观察组、对照组及安慰剂组 ３组

不良反应差异均无统计学意义（Ｐ＞００５）。见表 ６。

表 ６　各组不良反应比较［例（％）］

组别 有 无

观察组（ｎ＝１１６） ３（２６） １１３（９７４）

对照组（ｎ＝５８） ０（００） ５８（１０００）

安慰剂组（ｎ＝５７） １（１８） ５６（９８２）

３　讨论

目前，随着经济的飞速发展，食品种类丰富，人

们饮食习惯、结构及生活方式、节奏的变化，消化系

统疾病的发病风险越来越高［６］

。消化系统疾病主

要包括慢性非萎缩性胃炎、慢性萎缩性胃炎、急性胃

炎、消化道溃疡、功能性消化不良等疾病，是临床常

见病、多发病。据调查显示，我国在接受胃镜检查的

患者中，慢性胃炎约占 ９０％［７］

，并且根据一项横断

面调查显示，在各型慢性胃炎中，慢性非萎缩性胃炎

的内镜诊断率约为 ４９４％，慢性非萎缩性胃炎伴糜

烂的内镜诊断率高达 ４２３％，故对于慢性非萎缩性

胃炎，糜烂是其高发伴随状态［８］

。研究显示，慢性

非萎缩性胃炎伴糜烂症状易反复发作，可导致消化

性溃疡、上消化道出血、癌前病变，甚至胃癌等，不仅

严重影响了患者的生命质量，而且也加重了患者的

心理负担与经济负担［９］

。

中医学从整体出发，辨证施治，对于慢性非萎缩

性胃炎的治疗，不仅在一定程度上弥补了现代医学

治疗的不足，而且在缓解临床症状、延缓病情进展方

面具有一定优势，易被患者接受［１０］

。中医认为本病

的病因主要为脾胃虚弱、情志不畅、饮食不节等，病

变部位在脾胃，多夹郁热、络瘀、瘀热常合湿浊，虚实

夹杂尤为常见，故多采用清热凉血、化瘀散结、化湿

浊、敛疡生肌等治法［１１］

。

七蕊胃舒胶囊在临床上用于治疗慢性浅表性胃

炎伴糜烂湿热瘀滞证，功效化瘀除湿、导滞清热、生

肌止痛，具有中和胃酸，保护胃黏膜及促进溃疡愈合

等作用。七蕊胃舒胶囊由三七、酒大黄、枯矾和煅花

蕊石四味药组成，方中三七为君药，其性味甘、微苦，

温，为理血要药，具有止血不留瘀，化瘀不伤正的作

用。现代药理研究显示，三七的主要有效成分包括

三七总皂苷、三七素、黄酮、挥发油及微量元素等，具

有止血、活血、抗血栓、抗炎、镇痛等作用，其中活血、

止血之效可针对慢性浅表性胃炎伴糜烂湿热瘀滞证

的“瘀、毒”之邪发挥活血解毒之效；枯矾性味酸涩、

寒，为方中臣药，具有消痰，燥湿，止泻，解毒，杀虫的

功效，临床上对其多采取煅用，具有收敛溃疡创面、

生肌利水的功效，在治疗慢性浅表性胃炎伴糜烂中

发挥收敛糜烂的胃黏膜，促进胃黏膜修复的功效。

花蕊石性味酸涩、平，可化瘀止血，并能制酸止痛，为

佐药。《本草纲目》记载花蕊石：“治一切失血损伤，

其功专于止血，能使血化为水。”花蕊石主要化学成

分包括碳酸钙与氧化钙，可有效中和胃酸，保护胃黏

· ８３４１ · ＷＯＲＬＤＣＨＩＮＥＳＥＭＥＤＩＣＩＮＥ　Ｍａｙ．２０２２，Ｖｏｌ．１７，Ｎｏ．１０

膜。大黄为方中使药，味苦寒，主清热泻火、泻下攻

积、逐淤通经、凉血解毒等，其主要化学成分为大黄

素、大黄酸、大黄酚、芦荟大黄素、大黄素甲醚等，具

有抑菌、抗病毒、免疫调节、抗肿瘤等作用［１２］

。实验

研究显示，大黄可提高胃肠黏膜内的 ｐＨ值，改善胃

黏膜血流灌注，纠正胃肠缺血缺氧状态，并且大黄还

可清除组织及血浆内的炎症介质，降低胃黏膜的通

透性，防治胃肠感染［１３１４］

。此外，大黄中的主要有

效成分大黄素可引起幽门螺杆菌 ＤＮＡ损伤，影响幽

门螺杆菌芳胺乙酰转移酶的活性，从而发挥抗幽门

螺杆菌的作用［１５］

。方中三七活血行血；白矾与花蕊

石同用，收敛燥湿，促进胃黏膜修复；大黄通腑泻热，

解毒活血，诸药配伍使用，可活血化瘀，中和胃酸、保

护胃黏膜，有效治疗慢性非萎缩性胃炎伴糜烂。

本研究结果表明，观察组胃脘疼痛消失率高于

对照组及阳性药物组，且差异有统计学意义（Ｐ＜

００５）。观察组胃脘痞胀消失率与对照组接近，观

察组及对照组与安慰剂组胃脘痞胀消失率之间的差

异无统计学意义（Ｐ＞００５），但都高于安慰剂组的

５３１％。同时，观察组患者胃黏膜糜烂疗效、证候疗

效及幽门螺杆菌根除率均显著优于对照组及安慰剂

组，其中与安慰剂组差异有统计学意义（Ｐ＜００５）。

提示七蕊胃舒胶囊对慢性浅表性胃炎伴糜烂湿热瘀

滞证患者的胃脘疼痛、胃脘痞胀、胃部糜烂、纳呆少

食、口苦或口臭或黏、嘈杂、泛酸及幽门螺旋杆菌感

染具有良好的治疗效果，且改善效果优于三九胃泰

胶囊。此外，研究结果也表明观察组、对照组及安慰

剂组 ３组不良反应发生率低，且差异均无统计学意

义（Ｐ＞００５），提示七蕊胃舒胶囊治疗慢性浅表性

胃炎伴糜烂湿热瘀滞证具有良好的安全性。

综上所述，七蕊胃舒胶囊在治疗慢性浅表性胃

炎伴糜烂湿热瘀滞证方面临床疗效显著，尤其是在

改善胃脘疼痛、胃黏膜糜烂、中医证候及幽门螺旋杆

菌感染等方面，疗效优于对照药三九胃泰胶囊，并且

安全性较好，值得临床推广使用。

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［９］吴皓萌，黄绍刚，王凤云，等．基于胃微环境探讨中医药防治胃癌

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［１０］唐旭东，王凤云，张声生，等．消化系统常见病慢性非萎缩性胃

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（８）：３６１３３６１８．

［１１］王涛，王萍，迟伟．白长川从胃滞虚热论治慢性非萎缩性胃炎伴

糜烂［Ｊ］．辽宁中医杂志，２０１９，４６（４）：６９３６９５．

［１２］张桥，陈艳琰，乐世俊，等．大黄炮制的历史沿革及对化学成分、

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（３）：５３９５５１．

［１３］原凤蕉，李晓雪，尚海，李凌宇，宋艳玲，邹忠梅．芦荟大黄素吲

哚偶联物的合成及抗肿瘤活性研究［Ｊ］．中草药，２０２１，５２（０８）：

２２１７２２２５．

［１４］樊君，乔迪，陈广．大黄素对 ＬＰＳ诱导的心肌细胞炎症反应和细

胞凋亡的影响及机制［Ｊ］．中成药，２０２１，４３（３）：６３０６３５．

［１５］吴明慧，黄衍强，黄赞松，等．黄连素、大黄素、五味子及黄芩苷

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（２０２２－０３－１９收稿 本文编辑：吴珊）

世界中医药　２０２２年 ５月第 １７卷第 １０期 · ９３４１ ·

Journal of Ethnopharmacology 294 (2022) 115341

Available online 10 May 2022

0378-8741/© 2022 Elsevier B.V. All rights reserved.

Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule in

treating chronic non-atrophic gastritis: A multicentre, double-blind,

randomized controlled clinical trial

Hua-Fang Chen a,*

, Yang Gong b

, Zhijun Huang c

, Gang Zhao c

, Zhi-Min Chen d

, Yao-Ming Zen e

,

Hui-zhen Li f

, Yun-lian Hu g

a The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325000, PR China b General Hospital of the PLA Northern Theater Command, Liaoning, 110016, PR China c Children’s Drug Research Institute of Jianmin Group, Hubei, 430050, PR China d Ningbo Hospital of Traditional Chinese Medicine, Zhejiang, 315010, PR China e Wenzhou Hospital of Traditional Chinese Medicine, Zhejiang, 325000, PR China f The Second Affiliated Hospital of Tianjin Medical University, Tianjin, 300150, PR China g Hubei Provincial Hospital of Traditional Chinese Medicine, Hubei, 430060, PR China

ARTICLE INFO

Keywords:

Randomized controlled trial

Chronic non-atrophic gastritis

Damp-heat stasis syndrome

Traditional Chinese medicine

ABSTRACT

Ethnopharmacological relevance: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed

by an experienced doctor at Guang’anmen Hospital of China Academy of Chinese Medical Sciences. It has been

used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic

non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used

to treat them.

Aim of the study: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic nonatrophic gastritis with damp-heat stasis syndrome.

Materials and methods: This study was a multicenter randomized double-blind clinical trial with positive herbal

drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic

non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided

into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were

required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain

from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the

epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety

assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG).

Results: Both groups of subjects had a high level of medication adherence (defined as treatment completion for

over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The

QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain

(64.2%, 229/357vs 46.7%, 56/120; p < 0.001)，especially subgroupsubjects with moderate epigastric pain

(65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011)

and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/

177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/

Abbreviations: AE, adverse event; CG, chronic gastritis; CFDA, China Food and Drug Administration; CNG, chronic non-atrophic gastritis; CAG, chronic atrophic

gastritis; C-13or C-14, Carbon13 or Carbon 14breath test system; FAS, full analysis set; GC, Gastric cancer; GCP, Good Clinical Practice; GMP, Good Manufacturing

Practice; HPLC, High performance liquid chromatography; HP, helicobacter pylori; PNS, Panax notoginseng saponins; PPIs, proton pump inhibitors; PPS, per-protocol

analysis set; RCT, randomized controlled trial; SAE, serious adverse events; SS, safety analysis set; TCM, traditional Chinese medicine; V, visit.

* Corresponding author. The First Affiliated Hospital of Wenzhou Medical University, The Southern Baixiang, Ouhai, Wenzhoucity, Zhejiang Province, 325000, PR

China.

E-mail addresses: chenhuafang2011@126.com, chenhuafang@wmu.edu.cn (H.-F. Chen), gongyang126@126.com (Y. Gong), 452354589@qq.com (Z. Huang),

158200458@qq.com (G. Zhao), 155216714@qq.com (Z.-M. Chen), 250858111@qq.com (Y.-M. Zen), ctjenny@126.com (H.-z. Li), 843214365@qq.com (Y.-l. Hu).

Contents lists available at ScienceDirect

Journal of Ethnopharmacology

journal homepage: www.elsevier.com/locate/jethpharm

https://doi.org/10.1016/j.jep.2022.115341

Received 19 January 2022; Received in revised form 14 March 2022; Accepted 30 April 2022

Journal of Ethnopharmacology 294 (2022) 115341

2

82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than

those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events

related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p >

0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was

no discernible effect on heart, liver, kidney, or blood coagulation function.

Conclusion: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai

capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further

randomized, double-blind, placebo-control trial is warranted to verify its benefit.

1. Introduction

Chronic gastritis (CG) is a very common disease of the digestive

system. It can be categorized into non-atrophic gastritis, atrophic

gastritis, and special types of gastritis. Although the prevalence of

chronic non-atrophic gastritis (CNG), the most common type of CG, is

unknown in the general population, a national multi-center crosssectional study found that 49.3% (4389/8892) of patients with upper

gastrointestinal symptoms who underwent diagnostic upper endoscopy

from 33 centers had CNG (Du et al., 2014). Nonspecific dyspeptic

symptoms such as epigastric discomfort, distention, belching, acid

regurgitation, nausea, vomiting, loss of appetite, and energy are common in CNG patients. Based on its clinical manifestations, CNG can be

categorized as Weiwantong (stomach ache), Piman (abdominal distention), or Caoza (gastritis discomfort) in the field of traditional Chinese

medicine (TCM) (Tang et al., 2012).

Medications for CNG largely include antibiotics, gastric mucosal

protective agents, proton pump inhibitors (PPIs), prokinetics and antiacids (Fang et al., 2012). However, even with standard medications

therapy, the efficacy is less than satisfactory, and some adverse effects

may occur (den Hollander and Kuipers, 2012). Li’s study has shown that

long-term use of PPI may alter the colonization mode of helicobacter

pylori (Hp) and this could accelerate the process of gland loss and

subsequent process leading to the appearance of chronic atrophic

gastritis (Li et al., 2017), Besides, the eradication rate of Hp has

decreased due to the increase of antimicrobial resistance, poor compliance, and adverse effects (Graham and Fischbach, 2010). TCM has

recently become a research focus in particular contexts, can broaden the

therapeutic approaches to CNG (Li et al., 2013; Qin et al., 2013; Sun

et al., 2013).

QiruiWeishu capsule is herbal preparation prescribed by an experienced doctor at Guang’anmen Hospital of China Academy of Chinese

Medical Sciences and has been used clinically for more than 30 years.

The names of the QiruiWeishu capsule once used were the liweifu

capsule and gastritis capsule. When QiruiWeishu capsule was a hospital

preparation, its function was removing stasis and dehumidification,

guiding hysteresis and clearing heat, enriching and relieving pain, and

indications are abdominal pain, abdominal distension, nausea, such as

chronic non-atrophic gastritis with erosion dampness and heat stasis

syndrome to see the above symptoms. The relevant paper was published

more than 20 years ago (Ren J J., 1997)Ren’s paper includes the clinical

and experimental study of the QiruiWeishu capsule. In the clinical study,

129 stomachache patients caused by phlegm and blood stasis were

treated for 28–56 days. 100 cases in the test group were treated with

QiruiWeishu capsule and 29 cases in the control group with Western

medicine. The total effective rate and clinical curative rate of the QiruiWeishu group were 96.0% and 81.0%, respectively, while the control

group had 72.4% and 41.4%. The clinical curative rate in the QiruiWeishu group was higher than that of the Western medicine group (p

< 0.05). The experimental study (Ren J J., 1997) used four different rat

models: pure wine refined gastric mucosa damage, acetic acid burned

gastric ulcer, Hp infected gastric mucosa, and reflux gastritis eroded

gastric mucosa. 72 Wistar male rats with gastric mucosa injury caused

by alcohol, acetic acid and Hp, and 86 both male and female Wistar rats

with reflux gastritis, after treatment with QiruiWeishu capsule or control

drugs, according to the findings the effective dose in the rat study was

1.3–2.5 times the clinical dose (clinical dose about 75 mg/kg/day). In all

four models, the QiruiWeishu capsule was able to protect the gastric

mucosa from pure alcohol damage and promote gastric ulcer healing,

reduce gastric acid and gastric juice in the ulcer model, inhibit Hp,

reduce gastric cholic acid in the gastric reflux gastritis model, and protect the gastric mucosa. Ren’s study showed that QiruiWeishu capsule

has abetter effect in increasing the blood flow of gastric mucosa,

reducing cholic acid and gastric acid, inhibiting Hp, healing the model of

acetic acid ulcer and resisting gastric mucosa injury by the pure alcohol.

QiruiWeishu capsule is composed of four traditional Chinese medicines, including Panaxnotoginseng(Burkill) F. H. Chen(hereinafter

“Panax notoginseng”), Rheumofficinale Baill (hereinafter “Rheumofficinale”), Alum and Ophicalcitum in a certain proportion. The content of

7compositions in the QiruiWeishu capsule was determined in an analysis test study (Chen et al., 2020), (notogenoside R1, gensenoside Rg1,

aloe-emodin, rhein, emodin, chrysophanol and physcion) by high performance liquid chromatography (HPLC). Ginsenoside Rg1

(C42H72O14) as the active ingredient of quality standard should be

4.0–9.0 mg and not less than 4.0 mg per tablet. In addition, thin-layer

chromatography was also used to identify Rhubarb and Panax

notoginseng.

The plants studied complied with the relevant laws and regulations

of the national and local governments to protect biodiversity. Panax

notoginseng and Rheumofficinale are two widely used plant Chinese medicinal materials with many published literatures. A randomized

controlled trial (RCT) must be conducted to verify the effectiveness and

safety of hospital preparations to obtain marketing authorization, according to the China Food and Drug Administration’s (CFDA) requirements. To the marketing approval of innovating of TCM, a clinical

trial on QiruiWeishu capsule was carried out on the premise of obtaining

the approval of clinical trial by CFDA. In this study, the SanjiuWeitai

capsule was used as a controlled drug, to explore the efficacy and safety

of the QiruiWeishu capsule in treating CNG (Damp-heat stasis syndrome), and to seek an alternative and effective treatment for these

patients.

2. Methods and design

2.1. Study design

This was a multicenter, randomized, double-blind, positive drug

control and superiority test clinical trial, to evaluate the safety and efficacy of Qirui Weishu capsule in treating CNG with damp-heat stasis

syndrome. The clinical trial was approved by The State Food and Drug

Administration of China in 2001 with the approval number of

2001ZL094. After the completion of phase I and II, the registration

numberCTR20180969 (www.chinadrugtrials.org.cn) of phase III trial

was assigned by the Chinese Clinical Trial Registry on August 31, 2018.

Based on the completion of the phase I and phase II trial, this study

was the phase III clinical trial of the traditional herbal formula Qirui

Weishu capsule. The study was strictly conducted based on the requirements of clinical trials by the Declaration of Helsinki, Good Clinical

Practice Guidelines, the Drug Administration Law of the People’s Republic of China, and also in compliance with all laws governing new

H.-F. Chen et al.

Journal of Ethnopharmacology 294 (2022) 115341

3

TCM drugs. Each trial site has a sub-investigator who is responsible for

the quality of the clinical trial. All investigators had completed standard

training before the trial. The Ethics Committee of the PLA Northern

Theater Command’s General Hospital (Ethical Approval No. 2016-89)

and the Ethics Committees of the other 10 sites reviewed and

approved the trial’s protocol and informed consent. All subjects signed

informed consent before they were randomly enrolled. The clinical trial

protocol was formulated about relevant diagnosis and treatment

consensus. The TCM syndrome criteria, such as the Diagnosis and

Treatment of Chronic Gastritis with Integrated Traditional Chinese and

Western Medicine, were agreed upon (Zhang et al., 2004), and

Consensus on TCM Diagnosis and Treatment of Chronic Non-atrophic

Gastritis at Shenzhen in 2009 (Spleen, 2009). In 2015, the general

principles for clinical research in Chinese medicine were published:

General Principles for Clinical Research in New Chinese Medicine

(China, 2015); The Consensus on Chronic Gastritis in China in 2012 was

a consensus on chronic gastritis (Fang et al., 2012), the Fourth National

Consensus Report on the Management of Helicobacter Pylori Infection at

Jing Gang Shan on 2012(Liu et al., 2012), and National Symposium on

chronic gastritis: Trial of endoscopic classification and grading standards and treatment of chronic gastritis Opinion (Yu, 2004).

2.2. Key inclusion and exclusion criteria for the subject

Inclusion criteria: 1. Age ranges from 18 to 65, regardless of gender;

2. Diagnosis of CNG with erosion using Western medicine, including

clinical manifestations consistent with chronic gastritis, gastroscopybased diagnosis of chronic non-atrophic gastritis with erosion, and

pathological biopsy following gastroscopy sampling; 3. Diagnostic of

traditional Chinese medicine and the syndrome differentiation criteria

of dampness, heat, and stasis; 4. Epigastric pain score of 3 or above; 5.

Voluntary provision of written informed consent before enrollment.

Exclusion criteria：1.Chronic atrophic gastritis, other secondary

gastritis; gastric and duodenum ulcers, deep ulcers, arterial bleeding,

gastric mucosa with severe dysplasia or pathological diagnosis suspected malignant change; 2. Drugs related to CNG and erosion have been

used within one week before this screening; 3. Having a serious primary

heart, liver, lung, kidney, blood disease or a serious disease affecting

their survival, such as cancer, AIDS, or clotting disorders; 4. Laboratory

examination: Scr > N (N is the upper limit of normal value); ALT and

AST >1.5N; WBC <3.0 × 109/L; 5. Pregnantor plan pregnancy, lactation, women with menorrhagia; 6. Patients with chronic anxiety and

others were deemed unsuitable for the clinical trial.

2.3. Plant, mineral materials and drug preparation

The raw medicinal materials were purchased from Huirentang

Pharmaceutical Co., LTD., bozhou City, Anhui Province, China, with

batch number 110201, in which Panax notoginseng came from Yunnan

Province, wine Rheum officinale came from Gansu Province, dried Alum

and calcined Ophicalcitum came from Shandong Province.

QiruiWeishu capsules for clinical trials are prepared by Jianmin

Pharmaceutical Co., LTD., Wuhan City, Hubei Province, China. The GMP

No is HB20140083 (April 25, 2014 to April 24, 2019). The main

equipment is universal powder mill (30B), multi-directional motion

mixing machine (HD-400), cyclooxyethane sterilization (E0Q-4.7),

cabinet automatic capsule filling machine (NJP-2000B), flat aluminum

bubble cover packaging machine (DPP-260H2), main inspection instruments: DI0NEX P680 liquid phase chromatography and Waters

E2695 liquid phase chromatography. The QiruiWeishu capsule was

manufactured in strict accordance with GMP, and the quality stability

and impact of packaging materials on drug stability were tested using 13

batches of samples before the clinical trial, with all indicators meeting

the quality standards.

The preparation process of QiruiWeishu capsules was as follows: take

an appropriate amount of Panax notoginseng, calcined Ophicalcitum,

dried alum, and wine Rheum officinale, respectively crushed them into a

fine powder, passed through 100 mesh sieve, and sterilized the above

four fine powders respectively for standby. For every 1000 capsules,

weighed 190g Panax notoginseng, 160g dried alum, 80g calcined ophicalcitum, and 70g wine Rheum officinale according to the prescription

proportion, mixed them well and put them into No. 0 capsule. Each

QiruiWeishu capsule contains 0.19g Panax notoginseng, 0.16g dried

alum, 0.08g calcined ophicalcitum, and 0.07g wine Rheum officinale.

The loading capacity of each capsule was 0.5g, and the content based on

ginsenoside Rg1 (C42H72O14) of Panax notoginseng in each capsule

should not be less than 4.0 mg. A published paper related to the QiruiWeishu capsule (Chen et al., 2020) was to determine the content of 7

components in it by HPLC. In Chen’s study, the QiruiWeishu capsule is

referred to as gastritis capsule, a name previously used. On the premise

of confirming the accuracy and sensitivity of the detection method, the

average content percentages of 7 components in QiruiWeishu capsule in

6 batches of samples were measured as follows (%,n = 3):notogenoside

R1 was 0.39%, gensenoside Rg1 was 1.085%, aloe-emodin was 0.054%,

rhein was 0.081%, emodin was 0.094%, chrysophanol was 0.128 and

physcion was 0.025% in that study. An invention patent on the QiruiWeishu capsule determination method was approved (the patent

number is ZL201910594055), allowing for a more comprehensive

characterization and control of drug quality, as well as better ensuring

drug efficacy and safety.

2.4. Randomized, controlled and blind

According to the universally recognized effective, safe, comparable

and similar principle, the control drug was selected as SanjiuWeitai

capsule. SanjiuWeitai capsule is composed of Zanthoxylum nitidum

(Roxb.) DC., Paeonia abchasica Miscz. Ex Grossh., Salvia miltiorrhiza

Bunge, etc, produced by China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. It was purchased by the sponsor for clinical trials.

SanjiuWeitai capsule has been on the market in China for more than 20

years with the CFDA approval number Z44020705. It was included in

the catalog of the Drugs of National Basic Hospitalization Insurance in

2000, included in the Announcement of the State Food and Drug

Administration on the Protected Varieties of Traditional Chinese Medicine (No. 40) in January 2005, and was listed in the People’s Republic of

China Pharmacopeia (2015). In “Clinical Practice Guideline of Chinese

Medicine for Chronic Gastritis” (Tang et al., 2012), Sanjiu Weitai

capsule as Chinese patent medicine has been recommended. SanjiuWeitai capsule is similar to QiruiWeishu capsule in function and indication, and the intended dosage is the same, and it is a kind of traditional

Chinese medicine widely used in clinic (Yin et al., 1996). The TCM indications for stomachache caused by dampness and heat internalization,

qi stagnation, and blood stasis are the control drug SanjiuWeitai capsule,

which is used in chronic gastritis, including non-atrophic gastritis with

erosion. Those are consistent with the diseases of the subjects targeted

by the test drugs in this study. In He’s (He, 2013) a randomized, positive,

and placebo-controlled clinical study on the treatment of CNG, the results showed that the total effective rate in the SanjiuWeitai group was

75%, superior to 40% in the placebo group (p < 0.05). In the phase II,

three-arm clinical trial, QiruiWeishu capsule, SanjiuWeitai capsule

(positive control), and placebo was designed as 2:1:1. From October 16,

2012 to March 23, 2015, phase II trial included 116 cases in QiruiWeishu group, 58 cases in SanjiuWeitai group and 57 cases in placebo

group. The test drug was found to be superior to the positive control

drug in improving epigastric pain symptoms and repairing gastric

mucosal erosion, and even better than the placebo group. Therefore, the

phase III protocol was designed to include subjects 3:1 ratio between the

test drug and the positive control drug.

The specification of both the test drug and the control drug is 0.5 g

per capsule. To make blind testing possible, all drugs are concealed in

uniform, sealed, opaque capsules with the same label. Each drug is

labeled as QiruiWeishu capsule clinical trial drug with the same use,

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4

dosage, and storage conditions. The validity period varies by production

batch, and the sponsor and SanjiuWeitai pharmaceutical factory are the

manufacturers. The monitors and investigators remain blind, and these

drugs were managed by clinical trial drug managers at each site, who are

responsible for the receipt, storage, distribution, recall and return of

surplus drugs and empty packages of used drugs.

The study was conducted in collaboration with 11sites of hospitals in

China. The method of center stratification and block randomization was

adopted. Those who were not related to the clinical trial should complete the drug blindness and emergency letter preparation. The drug

number after random blindness was the random code, and the random

number of the drug was the unique identification number of the subject.

Each drug number was accompanied by an emergency letter for emergency blindness. The drug is assigned to each site based on the random

code of the sites, the sequence of the random code, and the number of

cases signed by the clinical trial agreement. Subjects were randomly

enrolled according to the chronological order of enrollment and drug

number order at every site.

2.5. Intervention

The study period consisted of visit (V) 1 to V6, V1 (− 7 to 0 days) for

screening, V2 (0 days) for baseline, V3 (7 ±1days of administration), V4

(14 ±2days of administration), V5 (28 ± 2 days of administration) for

treatment, and V6 (56 ± 5 days) for follow-up. Several subjects test

group: control group was 3:1. The test drug QiruiWeishu capsule was

0.5g, and the control drug SanjiuWeitai capsule was 0.5g too. The

dosage of the two groups was: oral 4 capsules each time, 2 times a day

(half an hour before breakfast and dinner), continuously take the medicine for 28 days. Subjects need to fill out daily diary cards containing

information about taking medications and symptoms of discomfort. At

each visit, gastroscopy, histopathological, pathology, Helicobacter pylori test, pregnancy test for women of childbearing age, related laboratory safety examinations, and electrocardiogram, B-ultrasound

examination were performed, as well as gastroscopy, histopathological,

pathology, Helicobacter pylori test, pregnancy test for women of

childbearing age, related laboratory safety examinations and electrocardiogram, B-ultrasound examination at screening and V5.

In order to improve the compliance, the investigators were detailedly

and fully informed of the trial procedures including interventions and

various hospital tests and examinations to be completed, as well as other

treatment options if subjects do not participate in the trial during the

informed consent at screening period, and acquired subjects fully willing

to participate and be able to complete the trial and sign the informed

consent. The sponsor will cover the costs of all trial examinations,

including two painless gastroscopy visits during the screening period

and four weeks after treatment, as well as transportation subsidies for

each visit to the hospital, on this basis.

2.6. Primary outcome and secondary outcomes

Primary efficacy indicators: the disappearance rate of epigastric pain

was observed after 28 days of administration. Secondary efficacy indicators: 1. The disappearance rate of epigastric distension; 2. The total

effective rate of TCM syndrome (the difference between the TCM syndrome score before and after treatment/the TCM syndrome score before

treatment). Objective efficacy indicators derived from gastroscopy, pathology, and Carbon13 or Carbon14 breath test system (C-13or C-14)

detection of Hp include 3–6 as follows; 3. Compared with baseline, after

28 days of administration, changes in gastric mucosal erosion grade and

the cured rate of gastric mucosal yerosion under gastroscop were

calculated. The cure refers to the disappearance of erosion. The significant effect was that the erosion grade reduced from grade 3 to grade 1.

The effect was that the erosion grade was reduced by 1 grade, which was

from grade 3 to grade 2, or from grade 2 to grade 1; 4. The overall cured

rate of gastroscopic gastric mucosa lesions was calculated using the

change in a total score of gastric mucosal lesions under gastroscopy after

28 days of administration compared to baseline. The total score of

gastric mucosal lesions was erythema plus erosion. The reduction of the

total score of gastroscopic lesions ≥95% was considered as cured,

reduction ≥70% was significantly effective and reduction ≥30% was

effective. Those not up to the above standards or even aggravated were

ineffective; 5. The efficacy of histopathological active inflammation and

chronic inflammation after 28 days of administration was evaluated and

the cured rate was calculated by comparing the baseline. Inflammation

disappeared in all biopsy specimens was cured. Mean reduction of active

inflammation score ≥70% was significantly effective and mean reduction≥30% was effective. Ineffective because it was not up to the above

standards or even aggravated. The mean score for active inflammation

was the sum of the scores for active inflammation at 5 biopsy sites

divided by 5. The evaluation criteria of chronic inflammation were

consistent with those for active inflammation; 6. Eradication rate of Hp.

Eradication of Hp refers to the change from positive to negative of Hp

tested by C13 or C14 UBT after treatment, while non-eradication refers

to the still positive of Hp. The percentage of Hp eradication cases in the

total cases of subjects taking drugs was called the Hp eradication rate.

2.7. Safety

The examination involved in clinical trials included physical examination (temperature, respiration, heart rate, blood pressure, height and

weight), electrocardiography, B-ultrasound of liver, bile, pancreas,

spleen and kidney), Hp test laboratory tests including blood cell count,

urinalysis, stool examination, fecal occult blood test, liver function

(AST, ALT, ALP, r-GT, T-BIL), renal function (BUN,Scr), and blood

pregnancy test (if applicable). According to the clinical manifestations

and TCM symptoms of the subjects, combined with the above examination results, the investigators observed the subjects’ disease and drug

safety.

2.8. Statistical analysis and data management

In this study, the superiority test was used, and the number of cases

needed was calculated using the results of the phase II trial. In the phase

II trial, the Primary outcome of disappearance rate of epigastric pain was

78.9% in the QiruiWeishu capsule and 42.2% in the SanjiuWeitai

capsule. Based on the superiority trial, when α﹦0.025 (unilateral test),

power of the test (1- β)﹦80%, the case ratio between QiruiWeishu group

and SanjiuWeitai group was 3:1, and the calculated sample size was

54:18. Taking into account the shedding rate and the requirements of

the phase III clinical trial, it is planned to include 360 cases in the QiruiWeishu capsule group and 120 cases in the SanjiuWeitai capsule

group, with a total number of 480 subjects.

The RAVE electronic data management system of Medidata Solution

was adopted, and the electronic CRF was prepared by the Clinical

Research Institute of Peking University. Remote online data collection

and management was carried out under the Technical Guidelines for

Electronic Data Collection in Clinical Trials designated by the China

Food and Drug Administration. After the data was reviewed in blind

mode, all the data was locked online, the locked database was downloaded and handed over to the statistics department for statistical

analysis.

The software was SAS9.4 (software installation point license number: 11202165). The sample size calculation software is PASS13. All

statistical tests are two-sided, and a P value less than or equal to 0.05

was considered statistically significant. Descriptive statistical analysis,

qualitative indicators were described in a frequency table, percentage,

or composition ratio; Quantitative indicators are described in terms of

mean, standard deviation, or median. The general conditions of the two

groups were compared using appropriate methods based on the types of

indicators. The group T-test was used for the comparison of quantitative

data between groups, the chi-square test or precise probability test was

H.-F. Chen et al.

Journal of Ethnopharmacology 294 (2022) 115341

5

used for the classification data, and the Wilcoxon rank-sum test, CMH

test will be used for the grade data.

3. Results

3.1. Study completion

During the screening period, each subject was diagnosed with

chronic non-atrophic gastritis with erosion and gastric mucosa pathology, and they met all inclusion criteria but not the exclusion criteria.480

patients enrolled, including 3 who did not receive treatment, 357 in the

test group, and 120 in the control group. 424 subjects completed the

trial, 318 in the test group and 106 in the control group. There were 53

unfinished cases, including 39 in the test group with withdrew rate of

10.9%, and 14 in the control group with withdrew rate of 11.7% (Fig. 1).

There was no significant difference in withdrew rate between two

groups (p > 0.05). The concomitant medication in QiruiWeishu group

was 22.1% (79 cases among 357), and SanjiuWeitai group was 24.2%

(29 cases among 120). There was no statistical significance in concomitant medication among the two groups (p > 0.05). Subjects with

medication adherence over 80% accounted was 98.3% (118/120) in

SanjiuWeitai group and 96.9% (346/357) in QiruiWeishu group

(Table 1), with no significant statistical difference between the two

groups (p > 0.05).

After 4 weeks of treatment, the completion of various examinations

was as follows: among 120 subjects in the control group and 357 subjects in QiruiWeishu group, subjects of SanjiuWeitai group who had

completed gastroscopy, histopathologic biopsy, C13 or C14 UBT were

106, 104, 106 respectively; and subjects of QiruiWeishu group who had

completed gastroscopy, histopathologic biopsy, C13 or C14 UBT were

306, 305, 318 respectively. Concerning safety indicators, including ECG,

blood, and urine laboratory examinations, the number of subjects in the

SanjiuWeitai group was 118, and that in the QiruiWeishu group was

355. When the baseline characteristics of subjects in the test group and

control group were compared, including demographic characteristics,

personal medical history, vital signs, symptoms, and signs of physical

examination of western medicine, graded of Chinese medicine symptom,

Hp test (13C or 14C-UBT), gastroscopy and histologic examination of

gastric mucosa tissue, excepting active inflammation of the lesser curvature and gastric angle, there was no significant difference between

two groups (p > 0.05) and the two groups were comparable.

3.2. Efficacy analysis

The full analysis set (FAS) of the main efficacy index: disappearance

Fig. 1. Flow chart of the trial.

Table 1

Medication adherence in this study.

Index Total Sanjiu Weitai Qirui Weishu

<80%n (%) 13 (2.7%) 2 (1.7%) 11 (3.1%)

80%-120%n (%) 464 (97.3%) 118 (98.3%) 346 (96.9%)

Total 477 120 357

p values 0.738

Statistics: Fisher exact probability method.

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6

rate of epigastric pain after 28 days of administration are shown in

Fig. 2a, and the mean scores of epigastric pain change from baseline to

visit5 were shown Fig. 2b, The lower 95%CI limit of the difference of

epigastric pain disappearance rate between the QiruiWeishu capsule

group and the SanjiuWeitai group was all greater than 0, and the QiruiWeishu capsule group was significantly better than the SanjiuWeitai

group (Table 2).

Table 3 shows the rates of epigastric pain disappearance in different

subgroups at baseline. For baseline mild and severe epigastric pain

subjects, there was no statistical significance in the disappearance rate of

epigastric pain between the test and control group (p > 0.05) after 28

days of administration, and for subjects with moderate baseline

epigastric pain, there was a statistically significant difference in the

disappearance rate of epigastric pain between the test and control group

(p < 0.05) after 28 days of administration, indicating that the test drug

had a higher disappearance rate of epigastric pain in improving moderate epigastric pain. There was no significant difference in the disappearance rate epigastric pain after 28 days of administration between

the QiruiWeishu group and the SanjiuWeitai group when the baseline

gastroscopy erythema was level 0 and 3 (p > 0.05), but the disappearance rate of epigastric pain in the QiruiWeishu group was better than

that in the SanjiuWeitai group, and the difference between the two

groups was statistically significant when the baseline gastroscopy erythema was level 1 and 2 (p < 0.05, p = 0.05). When the baseline

gastroscopy erosion was grade 1, and 3, there was no statistically significant difference in the disappearance rate of epigastric pain after 28

days of administration between the QiruiWeishu group and the SanjiuWeitai group (p > 0.05), however, when the baseline microscopic

erosion was grade 2, the disappearance rate of epigastric pain in the

QiruiWeishu group was better than that in the SanjiuWeitai group with

statistically significant (p < 0.05). There was no statistically significant

difference in the disappearance rate of epigastric pain after 28 days of

administration between QiruiWeishu group and SanjiuWeitai group

when Hp was positive at baseline (p > 0.05), in contrast, the Hp was

negative, the disappearance rate of epigastric pain in the QiruiWeishu

group was better than that in the SanjiuWeitai group with statistically

significant (p < 0.05). These findings suggest that the test drug is more

effective than the control drug in improving the rate of epigastric pain

disappearance in patients with grade 1 and 2 gastroscopy erythema,

grade 2 gastroscopy erosion, and Hp negative at baseline (p < 0.05).

The following is a summary of the results for the main efficacy indicators: The QiruiWeishu group had a significantly higher rate of

epigastric pain disappearance than the control group, and the superior

effect was established in the QiruiWeishu group compared to the SanjiuWeitai group, with the effect gradually emerging after two weeks of

medication. Especially for the patients with moderate epigastric pain,

grade 1 and 2 erythema under gastroscope, grade 2 erosion under

gastroscope and Hp negative patients, the efficacy of the QiruiWeishu

group in the disappearance rate of epigastric pain were more obvious.

Below are the results of secondary efficacy indicators. The scores of

TCM symptoms after 28 days of administration in the QiruiWeishu

capsule group were significantly lower than those in the SanjiuWeitai

group (Table 4 p < 0.05), and the improvement of TCM symptoms in the

Fig. 2. a. The disappearance rate of epigastric pain at visit 5; b. Mean scores of QiruiWeishu group was significantly better than that in the SanjiuWeitai

epigastric pain change from baseline to visit5.

Table 2

Primary outcome index the disappearance rate of epigastric pain at visit 5.

Index Sanjiu

Weitai

Qirui

Weishu

Rate difference Of

95% CI (%)

p

values

Not disappear n

(%)

64

(53.3%)

128

(35.9%)

Disappear n (%) 56

(46.7%)

229

(64.2%)

17.48 (7.26,27.70) <0.001

Aggregate

(Missing)

120 (0) 357 (0)

The lower limit of 95% CI of the difference between Qirui Weishu group and

Sanjiu Weitai group in the disappearance rate of epigastric pain was greater than

0, indicating that Qirui Weishu group had superior effect compared with Sanjiu

Weitai group.

Table 3

Epigastric pain disappearance rate at visit5-based on different subgroups at

baseline.

Grading at baseline Disappearance rate of epigastric pain (%) p values

Sanjiu Weitai Qirui Weishu

Mild- Epigastric pain 37/67 (55.2%) 136/208 (65.4%) 0.115

Moderate- epigastric

pain

14/46 (30.4%) 89/137 (65.0%) <0.001

Severe- epigastric pain 5/7 (71.4%) 4/12 (33.3%) 0.094

Erythema level 0 1/2 (50.0%) 2/3 (66.7%) 0.317

Erythema level I 42/81

(51.9%)

149/220 (67.7%) 0.011

Erythema level II 13/35

(37.1%)

70/121 (57.9%) 0.050

Erythema level III 0/2 (0.0%) 8/13 (61.5%) 0.414

Erosion level I 23/46 (50.0%) 88/142 (62.0%) 0.203

Erosion level II 25/57 (43.9%) 118/176

(66.7%)

0.002

Erosion level III 8/17 (47.1%) 25/36 (69.4%) 0.150

HP positive 20/36 (55.6%) 70/111 (63.1%) 0.426

HP negative 35/82 (42.7%) 155/237

(65.4%)

<0.001

HP did not test 1/2 (50.0%) 4/9 (44.4%) 0.808

Disappearance rate: the number of subjects with epigastric pain disappearance/

total number of subgroups subjects in Qirui Weishu or Sanjiu Weitai group.

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7

group. The reduction in total TCM syndrome score in the QiruiWeishu

group was more noticeable (p < 0.05) when compared to the baseline

data. The total effective rate of TCM syndrome were192 among 357

subjects with a total effective rate of 53.8% in the test group, 48 among

120 subjects with a total effective rate of 38.3% in the control group

after 28 days of administration (p < 0.05), so the total effective rate of

TCM syndrome at V5 in the test group was significantly better than that

in the control group (Fig. 3).

There was no significant difference in the disappearance rate of after

28 days of administration epigastric distension between the QiruiWeishu group and the SanjiuWeitai group (p > 0.05 Fig. 4a and b).

Compared with SanjiuWeitai, and the QiruiWeishu capsule showed no

obvious advantage in improving epigastric distension (Table 5).

As for objective indicators obtained by gastroscopy, pathology, and

C-13or C-14 examination, the QiruiWeishu capsule and the SanjiuWeitai

group were similar in efficacy. According to the criteria of cure, obvious

effectiveness, effectiveness and in effectiveness, of the secondary efficacy indicators in the trial protocol, the objective indicators generated

by each test after the subjects completed the 28-day administration were

classified, and the corresponding number of cases and percentage were

detailed shown in Table 6. As can be seen from the results, there were no

significant differences between the QiruiWeishu and SanjiuWeitai

groups in terms of mucosa erosion and overall gastric mucosal lesions

detected by gastroscope, improvement of active and chronic inflammation detected by histopathology, and elimination of Hp tested by C-13

or C-14 of subjects after 28 days of treatment.(Every p > 0.05).

There was no significant difference between the QiruiWeishu capsule

group and the SanjiuWeitai group. The eradication rate of Hp by C-13 or

C-14, as well as the cured rate of gastric mucosa erosion and overall

gastric mucosal lesions under gastroscope, active inflammation and

chronic inflammation by histopathology, and active inflammation and

chronic inflammation by histopathology (Table 7, every p > 0.05).

Comparing the clinical symptoms such as belching and eating less, it

was found that the QiruiWeishu group had better efficacy than the

SanjiuWeitai group, while the clinical symptoms such as bitter mouth,

Table 4

The total score of TCM syndromes at visit 5.

Total score of TCM syndromes Index Sanjiu

Weitai

Qirui

Weishu

Baseline intergroup comparison Median 11.00 11.00

Mean

(SD)

11.07

(3.26)

10.98

(3.16)

p values 0.849

Visit 5 intergroup comparison Median 4.00 3.00

Mean

(SD)

4.54 (3.92) 3.13

(2.93)

p values 0.002

Difference between visit5 and baseline

difference comparison intergroup

Median 6.00 8.00

Mean

(SD)

6.58 (4.16) 7.78

(3.88)

p values <0.001 <0.001

difference comparison 2 groups P values 0.002

95%CI 0.35,2.06

Rate of change between Median 0.63 0.77

visit5 and baseline Mean

(SD)

0.60 (0.34) 0.71

(0.28)

rate of change comparison intergroup p values <0.001 <0.001

rate of change comparison 2 groups p values 0.003

95%CI 0.05,0.17

Fig. 3. The effective rate of TCM syndrome between QiruiWeishu group and

SanjiuWeitai group.

Fig. 4. a. The disappearance rate of epigastric distension at visit 5; b. Mean

scores of epigastric distension change from baseline to visit5.

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8

bad breath, viscosity, noise, and pantothenic acid had similar efficacy

between the two groups. However, all clinical mono-symptom comparisons within the groups showed significant improvement compared

to baseline (p < 0.05). The results of the secondary efficacy indicators

were summarized as follows: the total score of TCM symptoms after 28

days of administration (4 weeks of administration) and the total

response rate of TCM symptoms in the QiruiWeishu group was significantly better than SanjiuWeitai group (p = 0.002), while there were no

significant differences in epigastric distention, erythema and erosion

under gastroscope, active or chronic inflammation of gastric mucosa and

Hp eradication between QiruiWeishu group and SanjiuWeitai group (p

> 0.05). However, the total score of TCM symptoms, epigastric distention, gastric mucosal erythema, and erosion scores under gastroscopy

were all significantly lower than baseline, and the gastroscopic indicators were significantly improved.

3.3. Safety analysis

Among 480 subjects (473 in the safety analysis set, 355 of test group,

and 118 of control group), 188 (39.8%) had at least one adverse event

(AE). The incidence of AEs was 38.9% (138/355) in the QiruiWeishu

group and 42.4% (50/118) in the SanjiuWeitai group. There was no

significant difference between the groups (p > 0.05). In this study, 8

subjects in the QiruiWeishu group withdrew due to AEs, and 2 cases in

the SanjiuWeitai group withdrew. Most of the AEs in this trial were mild,

123 cases in the QiruiWeishu group, accounting for 34.7%, and 46 cases

in the SanjiuWeitai group, accounting for 39.0%; There were 16 cases of

moderate AEs in the QiruiWeishu group, accounting for 4.5%, and 6

cases in the SanjiuWeitai group, accounting for 5.1%; There were three

cases of severe adverse events in the QiruiWeishu group, accounting for

0.9% of the total, and none in the SanjiuWeitai group. The outcomes of

adverse events were generally symptom improvement or return to the

normal range of test values. Among the AEs, the investigator determined

that 4.2% (20/473) were related to the trial drug. Among them, 3.9%

AEs (14/355) were related to the test drug, and 5.1% AEs (6/118) were

related to the control drug (Table 8). The common adverse events

identified by the investigators as possibly related to the trial drug were

mild increases in blood ALT, AST, and creatinine, changes in stool shape

and stool frequency, abdominal pain, and increased or decreased

menstruation.

There were 3 serious adverse events (SAE) during the trial, including

2 cases (1 chronic proctitis and 1 deep venous thrombosis of the lower

extremity) in the QiruiWeishu group and 1 case (diarrhea, which

occurred 20 days after stopping administration) in the SanjiuWeitai

group. The investigator determined that they were not related to the

trial drug.

Table 5

Epigastric distension disappearance rate.

Item-visit5 Index Sanjiu

Weitai

Qirui

Weishu

p

values

Disappearance rate of

epigastric distension

Not disappear

n (%)

50

(45.5%)

117

(35.7%)

Disappear n

(%)

60

(54.5%)

211

(64.3%)

0.068

Aggregate

(Missing)

110 (10) 328 (29)

Table 6

Remission or improvement of mucosa erosion and overall gastric mucosal lesions under gastroscope，active and chronic inflammation by histopathology

and eradicate condition of Hp by C-13 orC-14 after treatment at V5.

Item Index Sanjiu

Weitai

Qirui

Weishu

Remission of gastric mucosal erosion cured 43

(40.6%)

119

(38.9%)

obvious

effective

1 (0.9%) 4 (1.3%)

effective 17

(16.00%)

51

(16.7%)

ineffective 45

(42.5%)

132

(43.1%)

Total (miss) 106 (14) 306 (51)

p values 0.986

Improvement of overall effect of

gastric mucosal lesions

cured 6 (5.7%) 21 (6.9%)

obvious

effective

11

(10.3%)

27 (8.8%)

effective 41

(38.7%)

122

(39.9%)

ineffective 48

(45.3%)

136

(44.4%)

Total (miss) 106 (14) 306 (51)

p values 0.936

Improvement of active inflammation

detected by histopathology

cured 50

(48.1%)

161

(52.8%)

obvious

effective

0 (0.0%) 4 (1.3%)

effective 9 (8.6%) 16 (5.2%)

ineffective 45

(43.3%)

124

(40.7%)

Total (miss) 104 (16) 305 (52)

p values 0.384

Improvement of chronic

inflammation detected by

histopathology

cured 1 (1.0%) 3 (1.0%)

obvious

effective

2 (1.9%) 4 (1.3%)

effective 12

(11.5%)

39

(12.8%)

ineffective 89

(85.6%)

259

(84.9%)

Total (miss) 104 (16) 305 (52)

p values 0.924

Condition of Hp eradication Changed to

negative

15

(14.2%)

47

(14.8%)

still positive 35

(33.0%)

89

(28.0%)

All negative 52

(49.1%)

168

(52.8%)

No tests done 4 (3.7%) 14 (4.4%

Total (miss) 106 (14) 318 (39)

p values 0.812

Statistics: Fisher exact probability method.

Table 7

Cured rate of gastric mucosa erosion and overall gastric mucosal lesions under

gastroscope, cured rate of active and chronic inflammation by histopathology

and eradicate rate of Hp by C-13 orC-14.

Item-visit5 Index Sanjiu

Weitai

Qirui

Weishu

p

values

Cured rate of gastric mucosa

erosion

Not Cured n

(%)

63

(59.4%)

187

(61.1%)

Cured n (%) 43

(40.6%)

119

(38.9%)

0.761

cured rate of overall gastric

mucosal lesions

Not cured n

(%)

100

(94.3%)

285

(93.1%)

Cured n (%) 6 (5.7%) 21 (6.9%) 0.666

Cured rate of histopathology

active inflammation

Not cured n

(%)

54

(51.9%)

144

(47.2%)

Cured n (%) 50

(48.1%)

161

(52.8%)

0.675

Cured rate of histopathology

chronic inflammation

Not cured n

(%)

103

(99.0%)

302

(99.0%)

Cured n (%) 1 (1.0%) 3 (1.0%) 1.000

Eradicate rate of Hp Other n (%) 91

(85.8%)

271

(85.2%)

Eradicate n

(%)

15

(14.2%)

47

(14.8%)

0.874

Statistics: Fisher exact probability method.

Hp eradication: Change from positive to negative for Hp with C13 or C14 after

treatment .

Rate: The number of subjects cured or eradicated as a percentage of all subjects

who used drugs.

H.-F. Chen et al.

Journal of Ethnopharmacology 294 (2022) 115341

9

In this study, the number and incidence of adverse events related to

the trial drug were lower in the two groups, and there was no significant

difference between the two groups. No serious adverse reactions

occurred in the two groups. The test drug had no obvious effect on the

heart (electrocardiogram) urine stool routine (urine routine, urine sugar

urine RBC, stool routine, fecal academia) blood routine (blood WBC,

RBC, HGB, PLT, GRA, LYM) coagulation function (PT, APTT, TT, FIB)

liver and kidney function (AST, ALT, ALP, r-GT, Tbil, BUN, Scr). The

result display that the QiruiWeishu capsule has good safety.

4. Discussion

The basic theories of TCM contain rich integrated thoughts, and

dialectical thinking is just the essence of TCM, which was developed

through thousands of years of empirical testing and refinement. Zheng

(meaning TCM syndrome), is an integral and essential part of TCM

theory (Wang and Dong, 2017). It is a thousand-year-old key diagnostic

concept in TCM, defined as a pattern of symptoms and physical signs in a

patient at a specific stage during a disease (Cheng et al., 2014). The TCM

diagnosis of diseases is based on the pattern of the syndrome, which

reveals what treatment options are available and should be prescribed to

patients (You et al., 2021). Hospital is the cradle of the development of

TCM preparations, with the advantages of observing clinical efficacy

and carrying out clinical validation trials. Most of the hospital TCM

preparations are the experienced formulations of famous old traditional

Chinese medicine doctors in hospital after many years of clinical practice, or the classical preparations of traditional Chinese medicine. It has

the characteristics of repeated clinical practice and definite curative

effects, and it is also an important source of new drug research. Therefore, hospital preparation has become the focus of TCM preparation

research and development (Hu et al., 2019). There are many successful

cases in the promotion and industrialization of hospital preparations,

such as compound Danshen Dripping Pills, the first one clinically verified by the FDA of the United States, and SanjiuWeitai Granule, the "king

of stomach medicine", all come from hospital TCM preparations (He

et al., 2019).

Hospital preparations have been tested for clinical safety and effectiveness, and the price is inexpensive, however, it cannot be used in

other hospitals or sold on the market. As a result, the dosage of hospital

preparations is small, and the development is severely limited. The lack

of standardized clinical research data is the main bottleneck of preventing the transformation of hospital preparations. Currently, China’s

market share of international proprietary Chinese medicine is only 5%,

while enterprises from Japan, South Korea, and the United States, which

import Chinese medicine’s crude raw materials in large quantities from

China, control 90% of the global market share (Li et al., 2015).

The mode of new drug research and development is "B to B" (from

bench to bedside) in translational medicine, but the evaluation of TCM

efficacy should gradually rise from clinical observation to the clinical

validation study. That means another kind of reverse "B to B" (from

bedside to bench) of translational medicine (Liu, 2011). TCM’s proprietary Chinese medicine is an important intervention tool, as well as a

driver of TCM’s modernization, industrialization, and

internationalization. Proprietary Chinese medicine has the characteristics of stable nature, precise curative effect, relatively small toxic and

side effects, easy to take, carry, store, and so on. It is difficult for western

doctors to benefit from TCM techniques if they do not use proprietary

Chinese medicines. The research and development of new drugs for

some hospital preparations with good clinical efficacy and safety, as well

as those are not only beneficial to reducing investment risks, but also to

popularising and transforming hospital research achievements, maximizing their characteristics and advantages. Therefore, Proprietary

Chinese medicine is a good way to utilize, promote TCM, and spread

TCM culture.

The novel coronavirus pandemic has caused huge losses to people all

over the world. Lu’s study found evidence of widespread use of infection

control behaviors and modern medicines and TCM for treatment and

prevention of COVID-19 and respiratory symptoms, especially many

TCM preparations recommended in Chinese clinical guidelines (Lu et al.,

2021). TCM should not only play a role in the treatment of infectious

diseases all over the world, but it should also play a bigger role in the

treatmmon and recurrent diseases.

QiruiWeishu capsule in this study is a proprietary Chinese medicine

preparation for the treatment of chronic non-atrophic gastritis belonging

to a frequently-occurring disease. Many drugs for the digestive organs in

Western medicine are derived from medicinal herbs, so a herbal drug

with multiple components should be effective in treating a variety of

digestive complaints (Motoo et al., 1995).

QiruiWeishu capsule is made up of Panax notoginseng, Rheum officinale, Alum, and Ophicalcitum. Panax notoginseng is the dried root and

rhizome of the plant Panax notoginseng. Wine Rheumofficinale belongs to

Rheum palmatum, dried roots, and rhizoid prepared with wine. Dried

Alum is a sulfate mineral alingite processed and then calcined, mainly

containing aluminum potassium sulfate (KAl (SO4)2). Calcined Ophicalcitum is the calcined product of metamorphic rock serpentine marble,

mainly containing calcium carbonate (CaCO3) and calcium oxide (CaO).

The above four raw materials were identified according to the relevant

provisions of the pharmacopeia of the People’s Republic of China (2015

edition).

The Panax notoginseng tastes sweet and slightly bitter, which is warm

and belongs to the liver and stomach meridian. It treats hematemesis,

hematochezia, blood stasis, and swelling by dispersing blood stasis and

stopping bleeding, detumescence and pain relief, dispelling phlegm,

stopping bleeding without leaving blood stasis, and specializing in the

treatment of hematemesis, hematochezia, blood stasis, and swelling. It is

used for stomachache with mutual obstruction of phlegm and blood

stasis. Phlegm and blood stasis are treated together to cure the root

cause. Just as Chinese classic famous medicalbook Materia Medica

Seeking Truth (edited by Huang,G.X. in 1769) narrated that people only

know the function of hemostasis and pain, but they do not know that

pain is caused by blood stasis, blood is stopped by stasis dispersedness,

and the smell of Panax notoginseng is bitter and warm, which can

differentiate its blood stasis in the blood. According to Records of

Traditional Chinese and Western Medicine in Combination (edited by

Zhang, X.C. in1909), the blood magical pellets prepared by Panax

notoginseng and Ophicalcitum can treat vomiting, blood stasis, and

Table 8

Occurrence of adverse event（AE），adverse drug reaction（ADR） and serious adverse events (SAE).

Item Cases of Sanjiu Weitai n of Sanjiu Weitai percen-tage Cases of Qirui Weishu n of Qirui Weishu percen-tage P values

AE 70 50 42.4% 184 138 38.9% 0.516

ADR 6 6 5.1% 15 14 3.9% 0.601

AE unrelated drug 64 46 39.0% 169 127 35.8% 0.581

Withdrew due to AE 2 2 1.7% 8 8 2.6% 1.000

Withdrew due to ADR 1 1 0.9% 4 4 1.1% 1.000

SAE 1 1 0.8% 4 2 0.6% 1.000

SAE related drug 0 0 0 0 0 0 -

Withdrew due to SAE 0 0 0 0 0 0 -

The adverse reaction is defined as "definitely related, probably related, possibly related" to the drug.

H.-F. Chen et al.

Journal of Ethnopharmacology 294 (2022) 115341

10

bleeding in urine and stool. Panax notoginseng and Ophicalcitum are

both holy medicines for hemostasis and blood conversion, and they

remove blood stasis without harming new blood. The Chinese classic

famous medical book Compendium of Materia Medica (edited by Li, S.Z.

in 1578) recorded Panax notoginseng can hemostasis, dispersing blood,

calming pain, and treatment of vomiting blood, epistaxis, hemifacial.

Dried Alum is sour and astringent, cold in nature, and belongs to the

liver meridian. The Compendium of Materia Medica recorded Alum: spit

out phlegm and saliva, dry dampness and detoxify, chase saliva, stop

bleeding and settle pain, eat evil meat, and produce good meat."

Therefore, using dried Alum to help Panax notoginseng dispel phlegm,

stop bleeding and relieve pain is an auxiliary drug. Calcined Ophicalcitum has a pungent nature, enters the liver meridian. The Compendium of Materia Medica recorded that Ophicalcitum cures all blood loss

and damage, specialized in hemostasis, and can turn blood into the

water. Rheum officinale is bitter in flavor, cold in nature, and acts on the

spleen, stomach, large intestine, liver, and pericardium channels. The

chemical constituents of Rheum officinale are anthracenes (anthraquinones and anthrones), stilbenes, tannins, and so on. One of the effects of

Rheum officinale is affecting the digestive system (Liang et al., 2017).

Rheum officinale was described as both for Qi and blood, a wonderful

medicine to stop bleeding without leaving blood stasis in the Chinese

dical book Treat iseon Blood Troubles (edited by Tang, Z.H. in 1885).

The main ingredient in the QiruiWeishu capsule is Panax notoginseng,

which has a major therapeutic role; the other three ingredients were

auxiliary medicines. Blood stasis and phlegm can be removed, the

bleeding stopped, and pain relieved with a combination of drugs. It is

suitable for patients with stomach pain and stuffiness, noisy acid swallowing, vomiting, and less eating, dull tongue and greasy coating, dark

pulse, black stool, non-atrophic gastritis in western medicine, erosive

and hemorrhagic gastritis with phlegm and blood stasis syndrome.

The incidence of CG in China has exceeded 60% (Du et al., 2014).

CNG was the most common type of CG. According to the Consensus of

Chronic Gastritis in China (2017, Shanghai) formulated by the Gastroenterology Division of Chinese Medical Association, chronic gastritis

was classified as CNG and chronic atrophic gastritis (CAG) by endoscopy

and gastric mucosa pathology. The prevalence rate is slightly higher

than the infection rate of Hp in the local population, while the infection

rate of Hp in China is about 52.2%, among which CNG accounts for

49.4%. Hp infection accounts for more than 90% of CG cases and is the

most common cause of CNG (Sipponen and Maaroos, 2015)Without

effective treatment, patients may suffer from upper gastrointestinal

symptoms, influencing their normal life and work, and it may develop

into CAG, a precursor lesion of gastric carcinoma (Park and Kim, 2015).

Hp infection of the gastric mucosa is a major risk factor for both intestinal and diffuse gastric cancer (GC), as well as chronic inflammatory

responses that cause tissue damage (You et al., 2006). The gene hopZ

was expressed (in-frame gene; “status-on”) in 22/41 (53.7%) H. pylori

strains. Accordingly, a study investigating HopZ expression in

non-atrophic gastritis patients found hopZ “status-on” in 59% of patients

(Kennemann et al., 2012). The therapeutic purpose of CNG is to improve

these symptoms and reduce gastric mucosal inflammation, mainly by

eliminating Hp, antacids (H2-receptor antagonist or a proton pump inhibitor), mucosal protectants, antidepressants, and anti-anxiety drugs.

In Western medicine, the most common drugs are proton pump inhibitors (PPIs) and gastric mucosal protective agents. Standard Western

pharmacotherapy is ineffective for a variety of reasons, including an

increase in Hp antimicrobial resistance, poor patient compliance, and

PPI-related side effects (Yue et al., 2021). The strongest predictor of Hp

treatment failure appears to be antimicrobial resistance (Fischbach

et al., 2002). Li’s study suggests that long-term PPI use is associated with

increased rates of gastric atrophy in pooled data. There was a higher

presence of gastric atrophy (15.8%; statistically significant) in the PPI

group compared to the SanjiuWeitai group (13.3%) when they identified

13 studies that included 1465 patients under long-term PPI therapy and

1603 controls (Li et al., 2017).

The dosing scheme and duration chosen are limited by concerns

regarding safety and the patients’ tolerance, as well as maintaining a

high level of compliance (Graham and Fischbach, 2010). This study

didn’t retrieve exact data on adherence to western medicine treatment

for non-atrophic gastritis, only found that the medication adherence was

68.0% in the non-intervention group of 50 patients with chronic atrophic gastritis after 1 month of discharge (Wang.J.H., 2019).

This study had good medication compliance, with 98.3% (118/120)

in the SanjiuWeitai group and 96.9% (346/357) in the QiruiWeishu

group, according to the diary cards containing medication information

filled in by the subjects every day and detailed records of drug distribution and recycling for each subject. It may be related to the fact that

the symptoms of stomach discomfort disappeared or were relieved in

both groups, the drugs were well tolerated and ADRs were less after drug

use. There was no difference in medication compliance between the test

and control groups when compared, and both performed well. Some

previous studies have also shown that the efficacy of TCM in treating

chronic gastritis was superior to chemotherapy, including all subtypes,

and no serious side effects were found (Yan et al., 2019). In east Asia,

traditional Chinese medicine is widely recognized as an alternative to

the treatment of chronic gastritis (Qin et al., 2013; Tominaga and Arakawa, 2013). The results of this study confirmed that the QiruiWeishu

capsule was superior to SanjiuWeitai in terms of the disappearance rate

of epigastric pain, the improvement of TCM symptoms, and the total

effective rate of TCM symptoms after 28 days of medication. The formula of the QiruiWeishu capsule is completely different from the SanjiuWeitai, the molecular mechanisms of how plants and minerals act on

gastritis to improve the symptoms of the disease are complex. Some

studies have attempted to investigate these aspects of the QiruiWeishu

capsule’s treatment of CNG to raise awareness.

About the ethnopharmacology of QiruiWeishu capsule, Pharmacological studies have shown that over 100 chemical constituents have

been isolated from Panax notoginseng (Men et al., 2020), saponins are the

main physiological active components of Panax notoginseng (Long,

2013), and their pharmacological effects are mainly (Yang et al., 2005)

promoting blood circulation, anti-inflammatory, and analgesic effects.

The total saponins of Panax notoginseng have significant inhibitory effects on experimental thrombosis in rabbits and rats. Intravenous injection can significantly inhibit the diffusion of intravascular

coagulation, a decrease of platelet count, and an increase of fibrin

degradation products. Panax notoginseng saponins can reduce the number of inflammatory cells and protein exudation induced by carrageenan, as well as the increase in capillary permeability caused by acute

inflammation, inflammatory exudation, and tissue edoema, as well as

granulation tissue proliferation in late inflammation. In addition, the

total saponins of Panax notoginseng have an obvious antagonistic effect

on pain caused by chemical and heat stimulation, and it is an opioid

peptide-like receptor stimulant, but do not have side effects of addiction.

In chronic atrophic gastritis rats, notoginsenoside R1 treatment

reduced serum levels of interleukin (IL)-1 beta and IL-6 in a dosedependent manner. Additionally, the increased levels of prostaglandin

(PG)E2, nitric oxide synthase (NOS), and endothelin (ET) in chronic

atrophic gastritis rats were significantly decreased by notoginsenoside

R1 administration. Notoginsenoside R1 exerts a protective effect on

CAG, and it is a multi-target, multi-linked, comprehensive process (Luo

et al., 2019). Yu’s study confirmsHAD-B effectiveness both in vitro and

in vivo the extract ameliorated HCl/EtOH-induced gastritis symptoms

HangAmDan-B (HAD-B), which consist of Radix Panax notoginseng,

Cordyceps militaris, Cremastraappendiculata, Radix Panax ginseng,

calculus bovis, ipomoea batatas (Yu et al., 2013). The combination of

Panax notoginseng and aspirin potentiated the antiplatelet effect of

aspirin via the AA/COX-1/TXB2 pathway in platelets and mitigated

ASA-related gastric injury via the AA/PG pathway in the gastric mucosa

(Xi et al., 2021). Li’s study (Li et al., 2021) showed that: Notoginseng

Radix Et Rhizoma is the dried root of Panax notoginseng, Notoginseng

Radix Et Rhizoma saponin was given to Hp cells alone and found that it

H.-F. Chen et al.

Journal of Ethnopharmacology 294 (2022) 115341

11

was able to induce apoptosis and/or necrosis of Hp cells in a

time-dependence manner.

Free and conjugated anthraquinone derivatives, tannins, stilbene

glycosides, phenol glycosides, and phenyl butanone are the primary

components of Wine Rheum officinale. Tannins, such as anthraquinone

derivatives and gallic acid, have been found to be the most effective

components of Rheum officinale for astringency and hemostasis in

modern pharmacological studies (Zhu et al., 2016). The gentian rhein

acid in Rheum officinale has anti-inflammatory and analgesic effects,

α-catechin and gallic acid can increase platelet adhesion and aggregation function, to achieve the effect of hemostasis. The tannin of Rheum

officinale can reduce the secretion of gastric juice and decrease the free

acidity of gastric juice. Chen’s animal study showed that Rheum officinale could significantly improve gastrointestinal perfusion in normal

and haemorrhagicshock rats (Chen et al., 2000).

The calcination method improves Alum’s efficacy in drying, collecting dampness, healing sores, hemostasis and decay, and antibacterial

action. Dried alum is also effective in the treatment of modern medical

cholecystitis, cholelithiasis, intestinal adhesion, and other acute

abdominal and gastroenteritis diseases (Huang et al., 2010). Pharmacological studies have shown that (Jiang, 2012) the main pharmacological effects of dried Alum are astringent, anti-inflammatory, and

bacteriostatic.

According to pharmacological studies (Gong et al., 2013) calcined

Ophicalcitum has a coating enrich and complex effect, as well as blood

acerbity hemostatic effect, easy shattering, and increased solid acerbity

convergence effect. In addition, calcined Ophicalcitum mainly contains

calcium carbonate and calcium oxide, which can neutralize gastric acid

and protect the gastric mucosa. After calcination, the Ophicalcitum increases the calcium concentration. The blood vessel wall will be compacted as the calcium concentration in the blood rises, preventing

plasma exudation and promoting blood coagulation. Moreover, after

calcination processing, the content of harmful metal elements in the

Ophicalcitum such as Cu, Zn, and Pb also decreased significantly.

The future studies include the following: 1. The molecular mechanisms by QiruiWeishu capsule treating chronic non-atrophic gastritis

still are not been fully elucidated, which may be something we need to

explore in our future research. We also hope that the results of this study

may trigger further researches on the mechanisms of its curative efficacy; 2. Future clinical trials should use a large sample size randomized,

double-blind, placebo-controlled trial; 3. To see if longer periods of

medication, such as 8 or 12 weeks, are more effective at preventing

chronic non-atrophic gastritis recurrence; 4. Cost-effectiveness should

be investigated further in future research to see if the QiruiWeishu

capsule has a pharmacokinetic advantage in curative effect and price

ratio (Liu et al., 2006).

5. Conclusion

As a traditional empirical preparation, the efficacy and safety of the

QiruiWeishu capsule have been verified in this study. Subjects who took

QiruiWeishu capsules showed good safety and excellent medication

compliance, especially in alleviating epigastric pain and TCM syndrome

in treating chronic non-atrophic gastritis with Damp-heat stasis syndrome. This clinical trial indicates that the QiruiWeishu capsule may

provide a new safe and effective alternative for patients with chronic

non-atrophic gastritis with Damp-heat stasis syndrome.

Funding

We are grateful to the financial support from the National Science

and Technology Major Special Project of "Major New Drug Innovation"

(National Key New Drug Creation and Manufacturing Program, Ministry

of Science and Technology(CN)), project No 2018ZX09731-004.

Key Researchand Development of Hubei Province, Project No

2020BCA057.

CRediT authorship contribution statement

Hua-Fang Chen: Conceptualization, Formal analysis, Methodology,

Project administration, Software, Supervision, Writing – original draft,

Writing – review & editing. Yang Gong: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources,

Supervision, Validation. Zhijun Huang: Conceptualization, Investigation, Methodology, Resources, Supervision, Validation. Gang Zhao:

Conceptualization, Formal analysis, Methodology, Project administration, Resources, Supervision, Validation, Validation, Writing – original

draft, Writing – review & editing. Zhi-Min Chen: Conceptualization,

Methodology, Software, Writing – original draft, Writing – review &

editing. Yao-Ming Zen: Data curation, Investigation. Hui-zhen Li: Data

curation, Investigation. Yun-lian Hu: Data curation, Investigation.

Declaration of competing interest

The authors declare that they have no known competing financial

interests or personal relationships that could have appeared to influence

the work reported in this paper.

Acknowledgments

The authors thank all subjects and investigators of the 11 sites that

participated in this clinical trial. This clinical trial was supported by the

Jianmin Pharmaceutical Group Co., LTD. The sponsor provided funding

for trial drugs and research cost of clinical trials.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.

org/10.1016/j.jep.2022.115341.

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Journal of Ethnopharmacology 294 (2022) 115341

中药七蕊胃舒胶囊治疗慢性非萎缩性胃炎的疗效和安全性：

一项多中心、双盲、随机对照临床试验

陈华芳 a，*，巩阳 b，黄志军 c，赵刚 c，陈志敏 d，曾耀明 e，李慧臻 f，胡运莲 g

a温州医科大学第一附属医院，325000，中国浙江

b解放军北部战区总医院，110016，中国辽宁

c健民集团儿童药物研究所，430050，中国湖北

d宁波市中医院，315010，中国浙江

e温州市中医院，，邮编：325000，中国浙江

f天津医科大学第二附属医院，邮编：300150，中国天津

g湖北省中医院，邮编：430060，中国湖北

关键词：随机对照试验 慢性非萎缩性胃炎 湿热瘀阻证 中医学

摘要：

民族药理学关联：七蕊胃舒胶囊是由中国中医科学院广安门医院一位经验丰富的医生开出的中

药组方制成的中药制剂。它已经在临床上使用了 30 多年。腹痛、腹胀、恶心是慢性非萎缩性

胃炎伴糜烂湿热瘀阻证的常见症状，而这种中药制剂已被用于这些症状的临床治疗。

研究目的：验证七蕊胃舒胶囊治疗慢性非萎缩性胃炎伴湿热瘀阻证的临床疗效和安全性。

材料与方法：本研究为多中心、随机、双盲临床试验，以阳性中药三九胃泰胶囊为对照，进行

主要疗效优势试验。477 例经胃镜和病理活检确诊的慢性非萎缩性胃炎糜烂患者，按 3:1 的比

例随机分为七蕊胃舒胶囊组和三九胃泰组。在试验期间，受试者需要完成 28 天的药物治疗。

主要结果是从基线检查到 4 周时上腹部疼痛的消失率。在基线检查、治疗 1 周、2 周和 4 周以

及随访 8 周和 16 周时，评估上腹痛和中医症状评分；在基线检查和治疗 4 周后评估胃镜检查、

组织病理学和幽门螺杆菌试验。安全性评估包括血常规、肝肾功能、实验室检查凝血和心电图

（ECG）。