第十三期“科創(chuàng)中國”助力產(chǎn)業(yè)高質(zhì)量發(fā)展學(xué)術(shù)研討會

會議議程

會議時間：2022 年 7 月 30 日 14:30-17:30

會議地點：北京亞洲大酒店（二層錦仁廳）

騰訊會議號 241 402 716

會議主題：七蕊胃舒膠囊創(chuàng)新發(fā)展研討會

會議議程：

時間 內(nèi)容 發(fā)言人 主持人

14:00-14:30 會議簽到

14:30-14:40 主持人開場及參會專家介紹 張霄瀟

張霄瀟

14:40-14:50 中華中醫(yī)藥學(xué)會領(lǐng)導(dǎo)致辭 劉 平

14:50-15:10 “科創(chuàng)中國”中醫(yī)藥產(chǎn)業(yè)科技服務(wù)團項目 郭繼華

15:10-15:40 七蕊胃舒膠囊研究進展匯報 黃志軍

15:40-17:10 專家發(fā)言及討論 全 體

唐旭東

17:10-17:20 健民集團董事長致謝 何 勤

17:20-17:30 會議總結(jié) 唐旭東 張霄瀟

參會名單

【中華中醫(yī)藥學(xué)會】

劉 平 中華中醫(yī)藥學(xué)會副秘書長

張霄瀟 中華中醫(yī)藥學(xué)會發(fā)展研究辦公室主任

郭繼華 中華中醫(yī)藥學(xué)會發(fā)展研究辦公室

【脾胃病領(lǐng)域研討專家】

唐旭東 中國中醫(yī)科學(xué)院 副院長

季 光（線上） 上海中醫(yī)藥大學(xué) 校長

楊 倩（線上） 河北省中醫(yī)院 副院長

張聲生 首都醫(yī)科大學(xué)附屬北京中醫(yī)醫(yī)院 消化中心主任

李軍祥（線上） 北京中醫(yī)藥大學(xué) 消化病研究院院長

劉 力（線上） 陜西省中醫(yī)藥大學(xué) 原黨委書記

沈 洪（線上） 江蘇省中醫(yī)院 消化科主任

蘇娟萍（線上） 山西省中醫(yī)院 脾胃病科主任

李延萍（線上） 重慶市中醫(yī)院 主任醫(yī)師

【交叉學(xué)科研討專家】

張洪春 中日友好醫(yī)院醫(yī)療 保健部主任

趙瑞華 中國中醫(yī)科學(xué)院廣安門醫(yī)院 婦科主任

曹俊嶺（線上） 北京中醫(yī)藥大學(xué)東直門醫(yī)院洛陽醫(yī)院 執(zhí)行院長

華國棟 北京中醫(yī)藥大學(xué)東直門醫(yī)院 藥劑科主任

王麗霞 中國中醫(yī)科學(xué)院廣安門醫(yī)院 藥劑科主任

馬 勇 首都醫(yī)科大學(xué)國家醫(yī)療保障研究院 副研究員

席曉宇（線上） 中國藥科大學(xué)國家藥物政策與醫(yī)藥產(chǎn)業(yè)經(jīng)濟研究中心 研究員

【企業(yè)參會人員】

何 勤 健民藥業(yè)集團股份有限公司 董事長

黃志軍 健民藥業(yè)集團股份有限公司 副總裁

健民集團介紹

健民集團，始創(chuàng)于明崇禎十年（1637 年），原名“葉開泰”，解放前便

享有“初清三杰”、“中國四大藥號”的美譽，2004 年在上海證券交易所上

市。健民集團以發(fā)展中醫(yī)藥為核心，已成為全國重點中藥企業(yè)，并設(shè)有國家

企業(yè)技術(shù)中心、企業(yè)博士后科研工作站和研發(fā)中心，具備完善的自主研發(fā)能

力。公司為中華老字號企業(yè)，擁有“健民”、“龍牡”、“葉開泰”三大品

牌。公司入選“中國最有價值品牌 500 強”，綜合實力躋身全國醫(yī)藥企業(yè)百

強之列。

健民集團研發(fā)中心為湖北省最早的中藥研發(fā)機構(gòu)之一，中心擁有一批由

國務(wù)院特殊津貼專家、湖北省突出貢獻專家、武漢市專家、博士、碩士等各

類人才組成的技術(shù)梯隊，中、高級專業(yè)技術(shù)職稱人員占 60%以上，主要領(lǐng)導(dǎo)

及學(xué)科負責人均具備碩士、博士學(xué)歷，具有豐富的新藥研究開發(fā)經(jīng)驗。擁有

2000 多平米實驗大樓和 1000 平米中試車間，配備藥物制劑、提取、檢驗、

中試等實驗設(shè)備百余臺套，研發(fā)投入達工業(yè)收入的 3.5%以上。

健民集團十分重視企業(yè)的技術(shù)創(chuàng)新工作。1999 年，以集團公司藥物研

究所為基礎(chǔ)，健民集團聯(lián)合湖北大學(xué)、湖北中醫(yī)學(xué)院、原同濟醫(yī)科大學(xué)（藥

學(xué)院）、武漢市生物技術(shù)研究中心等科研院所，組建了武漢市中藥現(xiàn)代化工

程技術(shù)研究中心，專門從事中藥新藥、新技術(shù)的開發(fā)工作。2000 年，該中心

被湖北省科技廳批準為“湖北省中藥現(xiàn)代化工程技術(shù)研究中心”。公司被認

定為國家高新技術(shù)企業(yè)，并于 2002 年被國家人事部批準建立“企業(yè)博士后

科研工作站”。 研究院在加強內(nèi)涵建設(shè)的基礎(chǔ)上，不斷豐富“以政府為引

導(dǎo)、以企業(yè)為主體、以科研院所為技術(shù)依托”的“產(chǎn)、學(xué)、研”的合作模式。

中心凝聚了一批國內(nèi)一流的、以院士為負責人的新藥研究及工程化方面的專

家顧問；此外公司還與中科院昆明植物所、北京大學(xué)、香港理工大學(xué)、華中

科技大學(xué)、天津中醫(yī)藥大學(xué)、湖北中醫(yī)藥大學(xué)等 20 多家國內(nèi)外科研單位建

立了長期的戰(zhàn)略合作關(guān)系，豐富和提高了中心的創(chuàng)新能力和創(chuàng)新效率。

產(chǎn)品背景

七蕊胃舒膠囊由健民藥業(yè)集團股份有限公司自主研發(fā)、于 2021 年 12 月

31 日獲批生產(chǎn)的 1.1 類中藥新藥。其功能主治為活血化瘀，燥濕止痛，用于

輕中度慢性非萎縮性胃炎伴糜爛濕熱瘀阻證所致的胃脘疼痛，主要優(yōu)勢如下：

一、七蕊胃舒膠囊是“重大新藥創(chuàng)制”科技重大專項成果，為首個獲批

治療慢性胃炎的中藥 1.1 類新藥。

七蕊胃舒膠囊（原名利胃膠囊）源自經(jīng)典名方“硝石礬石散”、“化血

丹”加減，作為中國中醫(yī)科學(xué)院廣安門醫(yī)院院內(nèi)制劑應(yīng)用 30 多年，該項目

被列入了 2018 年度“重大新藥創(chuàng)制”科技重大專項，是國內(nèi)首個獲批治療

慢性胃炎的中藥 1.1 類新藥，為慢性胃炎的治療提供了新的治療選擇。

二、七蕊胃舒膠囊是適應(yīng)我國慢性胃炎疾病變化和治療的創(chuàng)新藥物。

慢性胃炎(CG)是由多種原因引起的胃黏膜的慢性炎癥，是消化系統(tǒng)常見

病之一。該病癥狀易反復(fù)發(fā)作，嚴重影響患者的生存質(zhì)量，如未能及時治療，

可進一步發(fā)展為慢性萎縮性胃炎、胃癌等，已逐漸引起臨床重視。

《中國慢性胃炎共識意見(2017 年)》提出，有癥狀者常見癥狀為上腹痛

(52.9%)、腹脹(48.7%)，慢性非萎縮性胃炎伴糜爛在各型慢性胃炎中比例為

42.3%，因此治療胃痛、改善胃黏膜糜爛是慢性胃炎主要的治療目標，七蕊胃

舒膠囊的臨床研究表明，其可以顯著止痛，有效修復(fù)胃黏膜。

三、七蕊胃舒膠囊是首個明確治療慢性非萎縮性胃炎伴糜爛的藥物。

《中國慢性胃炎共識意見(2017 年)》提出，慢性非萎縮性胃炎伴糜爛在

各型慢性胃炎中比例為 42.3%，該病癥發(fā)病率高，臨床常見?！堵晕秆字嗅t(yī)

診療專家共識意見(2017)》將慢性胃炎分為肝胃不和證、脾胃濕熱證、脾胃

虛弱證、胃陰不足證、胃絡(luò)瘀陰證，其中脾胃濕熱證、胃絡(luò)瘀阻證是胃黏膜

糜爛明顯、胃痛日久不愈的主要證型。而現(xiàn)有常見藥物說明書中尚無明確治

療慢性非萎縮性胃炎伴糜爛的中成藥，1.1 類中藥新藥七蕊胃舒膠囊是唯一

明確治療慢性非萎縮性胃炎伴糜爛濕熱瘀阻證所致的胃脘疼痛的中成藥。

四、七蕊胃舒膠囊的臨床研究證實，具有顯著止痛、修復(fù)胃黏膜的療效，

是治療慢性非萎縮性胃炎伴糜爛的有效藥物。

上市前的Ⅱ、Ⅲ期臨床研究結(jié)果證實，七蕊胃舒膠囊對于慢性非萎縮性

胃炎伴濕熱瘀阻證發(fā)揮了顯著的療效，胃脘疼痛消失率可達 78.9%，胃黏膜

糜爛痊愈率可達 65.3%，中醫(yī)癥候總有效率可達 74.74%。相較陽性藥物三九

胃泰、安慰劑，七蕊胃舒膠囊在胃痛消失率、中醫(yī)證候改善、胃黏膜活動性

炎癥等指標顯示顯著的效果及優(yōu)勢。

綜上所述，七蕊胃舒膠囊是首個獲批的治療慢性胃炎的1.1類中藥新藥，

也是首個明確治療慢性非萎縮性胃炎伴糜爛濕熱瘀阻證所致的胃脘疼痛的

中成藥，具有顯著止痛、修復(fù)胃黏膜的作用。本次會議將對七蕊胃舒膠囊的

創(chuàng)新發(fā)展進行探討，并期望為藥品生產(chǎn)企業(yè)制定生產(chǎn)發(fā)展計劃和國家衛(wèi)生行

政部門制定藥物政策提供參考，造福更多慢性胃炎患者！

目錄

一、七蕊胃舒膠囊上市歷程 .................................................. 1

1、產(chǎn)品基本信息........................................................ 1

2、國家級科創(chuàng)項目成果.................................................. 2

3、產(chǎn)品傳承性.......................................................... 2

4、立項目的與依據(jù)...................................................... 3

二、七蕊胃舒膠囊藥物研究 .................................................. 5

1、組方方解............................................................ 5

2、藥理學(xué)研究.......................................................... 5

3、藥效學(xué)研究.......................................................... 6

4、毒理學(xué)研究.......................................................... 7

三、七蕊胃舒膠囊臨床應(yīng)用 .................................................. 7

1、臨床療效............................................................ 7

2、臨床安全性.......................................................... 9

四、七蕊胃舒膠囊經(jīng)濟性分析 ............................................... 10

1、同類藥物對比....................................................... 10

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

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

五、 七蕊胃舒膠囊產(chǎn)品總結(jié) ................................................ 13

六、 七蕊胃舒膠囊證明性文件 .............................................. 14

【參考文獻】 ............................................................ 15

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

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一、七蕊胃舒膠囊上市歷程

1、產(chǎn)品基本信息

【通用名稱】七蕊胃舒膠囊

【藥品類別】中成藥

【成 分】三七、枯礬、煅花蕊石、酒大黃

【性 狀】本品為硬膠囊，內(nèi)容物為淺灰黃色至黃色的粉末；味澀、微苦。

【功能主治】活血化瘀，燥濕止痛。用于輕中度慢性非萎縮性胃炎伴糜爛濕熱瘀阻證所

致的胃脘疼痛，舌質(zhì)紫黯或瘀斑瘀點、舌苔黃膩、脈弦澀或弦滑。

【規(guī) 格】每粒裝 0.5g（相當于飲片 0.5g）

【用法用量】口服。一次 4 粒，一日 2 次，早晚餐前半小時服用。療程 4 周。

【不良反應(yīng)】臨床試驗期間受試者用藥后出現(xiàn)：月經(jīng)量增多或減少、肝生化指標升高、

腹痛、 腰痛、腸鳴亢進、大便次數(shù)增多、便溏、凝血功能異常、皮疹瘙癢、

尿蛋白異常等。

【禁 忌】1.孕婦及哺乳期婦女禁用。

2.正在接受透析治療者禁用。

3.對本品及所含成份過敏者禁用。

【生產(chǎn)企業(yè)】健民藥業(yè)集團股份有限公司

【批準文號】國藥準字 Z20210009

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2、國家級科創(chuàng)項目成果

七蕊胃舒膠囊為 2018 年度“重大新藥創(chuàng)制”科技重大專項成果，為中國首個獲批治

療慢性胃炎的 1.1 類創(chuàng)新藥，也是首個用于治療慢性非萎縮性胃炎伴糜爛濕熱瘀阻證所

致的胃脘疼痛的中藥創(chuàng)新藥。（詳細內(nèi)容請見附件）

3、產(chǎn)品傳承性

七蕊胃舒膠囊由三七、枯礬、煅花蕊石、酒大黃四味藥組成，共奏活血化瘀，燥濕

止痛之功。組方源自經(jīng)典名方《張錫純臨證用藥》“化血丹”、《金匱要略》“硝石礬石散”

加減。

七蕊胃舒膠囊組方作為中國中醫(yī)科學(xué)院廣安門醫(yī)院的院內(nèi)制劑（批準文號：京藥制

Z20063205），由該院消化內(nèi)科首任主任任俊杰教授研制，已在臨床上應(yīng)用了三十余年。在

作為醫(yī)院制劑用于臨床 30 余年間，其臨床療效與安全性得到了充分驗證。結(jié)果證明，該

產(chǎn)品治療慢性胃炎療效與安全性均很好，服用方便，能滿足廣大患者的需求。

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4、立項目的與依據(jù)

（1）立項目的

消化系統(tǒng)疾病作為常見病、多發(fā)病，其發(fā)病率占人口總數(shù)的約 30%[1]，該類疾病主要

包括慢性非萎縮性胃炎、慢性萎縮性胃炎、急性胃炎、消化道潰瘍、功能性消化不良等。

其中慢性非萎縮性胃炎發(fā)病率相對最高，其是慢性胃炎患者在接受內(nèi)鏡檢查時，內(nèi)鏡下

的一種疾病類型，是胃黏膜在各種致病因素作用下所發(fā)生的非萎縮性慢性炎癥性病變。

有些慢性非萎縮性胃炎患者還存在伴糜爛的情況，這是指內(nèi)鏡下可見胃黏膜上皮的完整

性受損，但病損不超過粘膜肌層的一種病變[2]。

我國飲食文化多樣，隨著經(jīng)濟的飛速發(fā)展，食品種類豐富，社會壓力加大，伴隨著人

們飲食習(xí)慣、結(jié)構(gòu)的變化，生活方式、節(jié)奏的改變，消化系統(tǒng)疾病的發(fā)病風(fēng)險越來越高。

并且隨著消化內(nèi)鏡技術(shù)的發(fā)展及消化內(nèi)鏡檢查的普及，臨床上慢性胃炎的檢出率逐年升

高。有調(diào)查顯示，我國在接受胃鏡檢查的患者中，慢性胃炎約占 90%[3]。2014 年，由中華

醫(yī)學(xué)會消化內(nèi)鏡學(xué)分會牽頭開展的一項橫斷面調(diào)查顯示，在各型慢性胃炎中，慢性非萎

縮性胃炎的內(nèi)鏡診斷率約為 49.4%，慢性非萎縮性胃炎伴糜爛的內(nèi)鏡診斷率達 42.3%[4]，

4

凌福斌等[5]研究發(fā)現(xiàn)，1792 例慢性非萎縮性胃炎伴糜爛的患者中，男女之比為 1.4:1，年

齡≤30 歲的占 5.2%，30～50 歲的占 47.9%，50～70 歲的占 41.5%，≥70 歲的占 5.4%，

表明高發(fā)病年齡段為 30～70 歲。張聲生[6]等對 960 例慢性非萎縮性胃炎患者進行的一項

流行病學(xué)研究發(fā)現(xiàn)，伴糜爛者約占 35.7%，可見對于慢性非萎縮性胃炎，糜爛是其高發(fā)伴

隨狀態(tài)。胃黏膜糜爛患者較未糜爛患者病程更長，復(fù)發(fā)率高，并與消化性潰瘍、胃出血、

病理炎癥程度等均有相關(guān)性。本病若不加以診治，病變不斷發(fā)展，病情可進一步發(fā)展為

慢性萎縮性胃炎、胃潰瘍、甚至胃癌等。因此，對于該疾病反復(fù)發(fā)作者的積極性干預(yù)不可

小視。

對于慢性非萎縮性胃炎的治療，中醫(yī)學(xué)一般從整體出發(fā)，采取扶正祛邪的原則辨證

施治，往往具有明顯的治療作用，在一定程度上彌補了現(xiàn)代醫(yī)學(xué)治療的不足，不僅在緩

解臨床癥狀、延緩病情進展方面頗有優(yōu)勢，而且具有復(fù)發(fā)率低、副作用少等優(yōu)點，這表明

中醫(yī)藥在治療慢性非萎縮性胃炎方面有著巨大的優(yōu)勢。中醫(yī)認為本病的病因主要有外邪

犯胃、飲食傷胃、情志不暢及脾胃素虛等，均可引起胃失和降而使本病發(fā)生。本病的病變

部位在胃，涉及脾，多夾郁熱、絡(luò)瘀、瘀熱常合濕濁，虛實夾雜尤為常見，故治療上應(yīng)遵

循依證而辨、隨證用藥的原則，以清熱涼血、化瘀散結(jié)、化濕袪濁、斂瘍生肌等治法，方

能提高臨床療效[7]。

本制劑基于以上分析，從疾病的病因病機出發(fā)，科學(xué)組方，將中醫(yī)辨證與現(xiàn)代醫(yī)學(xué)

相結(jié)合而開發(fā)，并作為醫(yī)院制劑在臨床應(yīng)用多年，其臨床療效與安全性得到了充分驗證。

結(jié)果證明，該產(chǎn)品治療慢性非萎縮性胃炎療效與安全性均很好，服用方便，能滿足廣大

患者的需求。為此，本制劑適合開發(fā)為中藥新藥產(chǎn)品，向全社會推廣。

（2）立項依據(jù)

慢性非萎縮性胃炎的中醫(yī)辨證分型尚無統(tǒng)一標準?！堵苑俏s性胃炎中西醫(yī)結(jié)合

診療共識意見（2017年）》中，將其分為脾胃濕熱證、肝胃不和證、寒熱錯雜證、脾氣

虛證、脾胃虛寒證等證型[8]?！断到y(tǒng)常見病慢性非萎縮性胃炎中醫(yī)診療指南》中，將

其分為肝胃氣滯型、肝胃郁熱型、脾胃濕熱型、脾胃虛寒型、胃陰不足型、胃絡(luò)瘀阻型

等證型[9]。由于糜爛性胃炎是一種內(nèi)生瘡瘍，遵照《內(nèi)經(jīng)》諸痛瘡瘍，皆屬于“火”的

病機，故在辨證的基礎(chǔ)上主以清熱瀉火、生肌斂瘡的方法[10]。因此，慢性非萎縮性胃炎

伴糜爛主要由濕熱瘀滯導(dǎo)致，其治療當以化瘀除濕、導(dǎo)滯清熱、生肌止痛為法，目的是

去除病因，并緩解癥狀。本制劑七蕊胃舒膠囊則是針對慢性非萎縮性胃炎伴糜爛濕熱瘀

滯者所組方。

5

二、七蕊胃舒膠囊藥物研究

1、組方方解

七蕊胃舒膠囊由三七、枯礬、煅花蕊石、酒大黃四味藥材組成。方中三七甘緩溫通，

苦降下泄，能散瘀止血，消腫定痛，用于瘀血阻滯之胃痛癥?！侗静菥V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療作用，為方中君藥?？?/p>

礬消痰，燥濕，止瀉，解毒，殺蟲。《本草綱目》云：“吐下痰涎飲癖，燥濕解毒，追涎，

止血定痛，食惡肉，生好肉”?？莸\助三七燥濕生肌、消腫定痛，為臣藥。煅花蕊石化瘀

止血，并能制酸止痛，為佐藥。《本草綱目》記載煅花蕊石：“治一切失血損傷，其功專于

止血，能使血化為水”。酒大黃味苦、氣香、性涼，調(diào)氣止痛，清上焦血分熱毒，引胃氣

下行?！缎l(wèi)生寶鑒》卷二十三中記載：“酒煨大黃苦寒，引苦性上行至巔，驅(qū)熱而下”?？?/p>

見，酒大黃能引藥上行，驅(qū)熱下達，清血分熱，為方中使藥。諸藥相合，化瘀除濕，導(dǎo)滯

清熱，生肌止痛，用于慢性非萎縮性胃炎伴糜爛濕熱瘀滯證，癥見胃脘疼痛，胃脘痞脹，

噯氣，納呆少食，口苦，嘈雜，泛酸等。

2、藥理學(xué)研究

三七主要成份有三七總皂苷、三七素（三七氨酸）、黃酮、揮發(fā)油、氨基酸、糖類等

。藥理研究表明，皂苷類成分是三七主要的生理活性成分[11]，其藥理作用主要為[12]：活血

作用，三七總皂苷對家兔、大白鼠實驗性血栓形成均有明顯抑制作用；靜脈注射可以明

顯抑制凝血所致彌漫性血管內(nèi)凝血，動物血小板數(shù)目的下降和纖維蛋白降解產(chǎn)物的增加

。抗炎鎮(zhèn)痛作用，三七總皂苷能明顯抑制角叉菜膠誘導(dǎo)的炎細胞增多和蛋白滲出，對急

性炎癥引起的毛細血管通透性升高、炎性滲出和組織水腫以及炎癥后期肉芽組織增生也

均有抑制作用。此外，三七總皂苷對化學(xué)性和熱刺激引起的疼痛均有明顯的對抗作用，

且三七總皂苷是一種阿片肽樣受體刺激劑，但不具有成癮的副作用。

枯礬為白礬煅制品，具有收濕斂瘡、止血化腐的功效。用于濕疹濕瘡、脫肛、痔瘡、

聤耳流膿、陰癢帶下、鼻衄齒衄、鼻瘜肉。另外，枯礬單味或經(jīng)適當配伍，可治嘔吐、泄

瀉、胃痛、腹痛、脅痛等證。對現(xiàn)代醫(yī)學(xué)的膽囊炎、膽石癥、腸粘連等急腹癥及急性胃腸

炎亦有良效[13]。藥理研究表明[14]，枯礬的主要藥理作用有收斂消炎、抑菌等作用?？蓮募?/p>

胞中吸收水分，使細胞發(fā)生脫水縮合，減少腺體分泌，減少炎癥滲出物，又可與蛋白質(zhì)結(jié)

合成難溶于水的蛋白化合物而沉淀，使組織或創(chuàng)面呈現(xiàn)干燥，起到收斂燥濕的作用，是

6

中醫(yī)常用的外用收斂藥。而三七具有活血化瘀、去瘀生新的功效。兩藥合用能共奏祛瘀

燥濕、斂瘡生肌之功效，促進傷口愈合。實驗證明，枯礬、三七兩味中藥共同作用能明顯

縮短傷口的祛腐生肌時間，抑制細菌、病毒等微生物感染，促進傷口肉芽組織生長，對治

療傷口潰爛具有明顯的優(yōu)勢。

煅花蕊石為花蕊石的炮制品，花蕊石主含碳酸鈣（CaCO3），炮制后的煅花蕊石為碳酸

鈣及氧化鈣的混合物，藥理研究表明[15]：煅花蕊石有護膜生肌和絡(luò)之效，并具有化瘀收

澀止血的作用，易于粉碎，固澀收斂作用增強。此外，因煅花蕊石主含碳酸鈣及氧化鈣，

可中和胃酸，保護胃黏膜。

酒大黃為大黃的酒炙品，具有瀉下攻積，清熱瀉火，涼血解毒，逐瘀通經(jīng)，利濕退黃

的功效。善清上焦血分熱毒，用于目赤咽腫、齒齦腫痛。主要成分為游離型和結(jié)合型蒽醌

類衍生物、鞣質(zhì)類、二苯乙烯苷類、苯酚苷類和苯丁酮類等?，F(xiàn)代藥理研究表明[16]，蒽醌

類衍生物及沒食子酸等鞣質(zhì)為大黃收斂、止血作用的主要有效成分。大黃經(jīng)酒炙后，善

清上焦之火，主要起清胃火，清熱導(dǎo)滯、活血化瘀的作用。

以上論述表明，方中三七活血行血；枯礬與煅花蕊石同用，收斂燥濕，促進胃黏膜修

復(fù)；酒大黃通腑瀉熱，解毒活血。諸藥配伍使用，對慢性非萎縮性胃炎伴糜爛基本病機中

的“瘀血、熱毒、濕熱之邪”發(fā)揮治療作用，收斂燥濕，生肌止痛，并能中和胃酸，保護

胃黏膜。結(jié)合方解，表明本制劑組方合理，可用于慢性非萎縮性胃炎伴糜爛的治療。

3、藥效學(xué)研究

七蕊胃舒膠囊在北京醫(yī)科大學(xué)第三醫(yī)院開展了藥效學(xué)研究，各項研究顯示其用于慢

性胃炎治療具有顯著的作用機制，具體如下所述：

（1）止痛：通過冰醋酸誘發(fā)小鼠腹痛模型研究驗證了七蕊胃舒膠囊顯著減少小鼠扭體次

數(shù)，呈現(xiàn)顯著的止痛作用；

（2）改善胃黏膜：顯著增加酒精灌胃大鼠胃黏膜血流量，抵抗純酒精對胃黏膜的損傷，

促進潰瘍的愈合，展現(xiàn)出一定的胃黏膜改善作用；

（3）抑制胃酸分泌：顯示具有一定的降低總酸排出量的作用，可促進潰瘍愈合，輕度抑

制胃酸分泌；

（4）抗幽門螺旋桿菌：通過菌落培養(yǎng)、枸櫞酸鉍鉀陽性對照顯示七蕊胃舒膠囊對幽門螺

桿菌生長具有一定的抑制作用。

7

4、毒理學(xué)研究

本制劑急性毒性試驗及連續(xù)給藥 11 周的長期毒性試驗結(jié)果顯示，七蕊胃舒膠囊對小

鼠灌胃給藥的最大耐受量（MTD）為 32g 生藥/kg，相當于臨床劑量的 450 倍。給大鼠灌

胃低劑量（1.9g/kg/d）和高劑量（3.8g/kg/d）的利胃膠囊，連續(xù)給藥 11 周，未見毒性

反應(yīng)情況，對血常規(guī)和血液生化各項指標以及內(nèi)臟均無影響，表明七蕊胃舒膠囊無明顯

毒性作用的最高劑量（NOAEL）為 3.8g/kg/d，相當于臨床劑量的 50 倍。由此可見，七蕊

胃舒膠囊具有很好的安全性。

三、七蕊胃舒膠囊臨床應(yīng)用

1、臨床療效

（1）第一次Ⅱ期臨床研究

江蘇省中醫(yī)院、山東中醫(yī)藥大學(xué)附屬醫(yī)院、湖北中醫(yī)學(xué)院附屬醫(yī)院、山西省中醫(yī)藥

研究院 、陜西省中醫(yī)藥研究院附屬醫(yī)院 5 家中心參與了第一次Ⅱ期臨床研究。本試驗納

入符合慢性非萎縮性胃炎伴糜爛的診斷及中醫(yī)濕熱瘀滯證辨證標準的患者 240 例，設(shè)七

蕊胃舒膠囊組 120 例、陽性對照組（三九胃泰膠囊組）120 例。兩組均為口服藥物，服藥

方法為：試驗組七蕊胃舒膠囊+安慰劑，對照組三九胃泰膠囊+安慰劑，一日 2 次，治療

周期為 28 天。具體試驗結(jié)果如下：

①主要療效指標：

組別 七蕊胃舒膠囊組 三九胃泰組

胃脘疼痛消失率 80.17%

**

57.98%

胃脘痞脹消失率 72.57%

**

45.69%

胃黏膜糜爛有效率 67.89%

*

57.57%

注：與三九胃泰組相比，*

P＜0.05，

**

P＜0.01

②次要療效指標：

組別 七蕊胃舒膠囊組 三九胃泰組

證候療效有效率 80.84%

**

52.50%

Hp 改善率 42.2%

△

34.34%

注：與三九胃泰組相比，*

P＜0.05，

**

P＜0.01

8

上述試驗結(jié)果顯示七蕊胃舒膠囊相較于陽性對照藥三九胃泰，在胃脘疼痛消失率、

胃脘痞脹消失率、胃黏膜糜爛有效率、證候療效顯效率、HP 根除率等指標方面展現(xiàn)顯著

的療效及優(yōu)勢。

（2）第二次Ⅱ期臨床研究[17]

江蘇省中醫(yī)院、甘肅省中醫(yī)院、河北省中醫(yī)院、長春中醫(yī)藥大學(xué)附屬醫(yī)院、天津中醫(yī)

藥大學(xué)第一附屬醫(yī)院 5 家中心參與了第二次Ⅱ期臨床研究。本試驗納入符合慢性非萎縮

性胃炎伴糜爛的診斷及中醫(yī)濕熱瘀滯證辨證標準的患者 240 例，設(shè)七蕊胃舒膠囊組組 120

例、陽性對照組（三九胃泰膠囊組）與安慰劑對照組各 60 例。三組均為口服藥物，每次

4 粒，一日 2 次，治療周期為 28 天。具體試驗結(jié)果如下：

①主要療效指標：

組別 七蕊胃舒膠囊組 三九胃泰組 安慰劑組

胃脘疼痛消失率 78.9%*△

42.2% 28.6%

胃脘痞脹消失率 65.3% 68.9% 53.1%

胃黏膜糜爛有效率 80%*△

55.6% 53.1%

注：與三九胃泰組相比，*

P＜0.05；與安慰劑組相比，△

P＜0.05

②次要療效指標：

組別 七蕊胃舒膠囊組 三九胃泰組 安慰劑組

證候療效顯效率 74.74%*△

57.78% 30.61%

Hp 根除率 52.7%△

34.6% 22.6%

注：與三九胃泰組相比，*

P＜0.05；與安慰劑組相比，△

P＜0.05

上述試驗結(jié)果顯示七蕊胃舒膠囊相較于陽性對照藥三九胃泰、安慰劑，在胃脘疼痛

消失率、胃脘痞脹消失率、胃黏膜糜爛有效率、證候療效顯效率、HP 根除率等指標方面

展現(xiàn)顯著的療效及優(yōu)勢。

（3）Ⅲ期臨床研究[18]

由中國人民解放軍沈陽軍區(qū)總醫(yī)院牽頭的 11 家中心參與了Ⅲ期臨床研究。本次研究

共納入符合慢性非萎縮性胃炎伴糜爛的診斷及中醫(yī)濕熱瘀滯證辨證標準的患者標準的

480 例患者，其中七蕊胃舒膠囊組 360 例，三九胃泰膠囊對照組 120 例。兩組組均為口服

藥物，每次 4 粒，一日 2 次，治療周期為 28 天。具體試驗結(jié)果如下：

①主要療效指標：

9

組別 七蕊胃舒膠囊組 三九胃泰組

上腹痛消失率 64.2%

*

46.7%

輕度上腹痛消失率 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：與三九胃泰組相比，*

P＜0.05，**P＜0.01

②次要療效指標：

組別 七蕊胃舒膠囊組 三九胃泰組

中醫(yī)癥候總有效率 53.8%

*

38.3%

胃脘痞脹消失率 64.3% 54.5%

胃黏膜糜爛有效率 56.9% 57.5%

活動性炎癥痊愈率 52.8% 48.1%

慢性炎癥痊愈率 1.00% 0.97%

注：與三九胃泰組相比，*

P＜0.05

上述試驗結(jié)果顯示七蕊胃舒膠囊在研究中展現(xiàn)出了顯著的治療效果，尤其是在緩解

胃脘疼痛及中醫(yī)證候改善方面效果顯著且優(yōu)于對照藥物三九胃泰，并能改善胃鏡下胃粘

膜紅斑、糜爛表現(xiàn)以及胃脘痞脹、噯氣、納呆少食、口苦、嘈雜、泛酸等癥狀。

2、臨床安全性

（1）Ⅱ期臨床研究[17]

江蘇省中醫(yī)院、甘肅省中醫(yī)院、河北省中醫(yī)院、長春中醫(yī)藥大學(xué)附屬醫(yī)院、天津中醫(yī)

藥大學(xué)第一附屬醫(yī)院 5 家中心參與的Ⅱ期臨床研究，統(tǒng)計和分析了納入研究的 240 例受

試者安全性數(shù)據(jù)。

七蕊胃舒膠囊組有 3 例（2.5%）發(fā)生了與研究藥物有關(guān)的不良反應(yīng)，其中 2 例表現(xiàn)

為月經(jīng)量增多（１例可能與試驗用藥有關(guān)，另１例與試驗藥物關(guān)系為可疑）；１例表現(xiàn)為

肝功能改變（與試驗用藥關(guān)系可疑）；對照組、安慰劑組各有１例發(fā)生不良事件（與試驗

藥物無關(guān)）；觀察組、對照組及安慰劑組 3 組不良反應(yīng)差異均無統(tǒng)計學(xué)意義（Ｐ＞0.05）。

（2）Ⅲ期臨床研究[18]

中國人民解放軍沈陽軍區(qū)總醫(yī)院牽頭的 11 家中心參與的Ⅲ期臨床研究，統(tǒng)計和分析

10

了納入研究的 240 例受試者安全性數(shù)據(jù)。本試驗所發(fā)生的不良事件中，經(jīng)研究者判定 4.23%

（20/473）與試驗藥物有關(guān)。其中七蕊胃舒膠囊組發(fā)生 15 例次（14 例，3.94%）不良事

件與試驗藥有關(guān)，對照組發(fā)生 6 例次（6 例，5.08%）不良事件與對照藥有關(guān)。輕度不良

反應(yīng)試驗組為 12 例次（11 例），發(fā)生率 3.10%，對照組 5 例次（5 例），發(fā)生率 4.24%，

兩組間差異無統(tǒng)計學(xué)意義（P>0.05）。中度不良反應(yīng)試驗組為 3 次（3 例），對照組 1 例

次，發(fā)生率均為 0.85%，兩組間差異無統(tǒng)計學(xué)意義（P>0.05）。兩均未發(fā)生嚴重的不良反

應(yīng)。本試驗試驗組 4 例受試者因不良反應(yīng)而前退出，對照組 1 例前退出。本試驗期間發(fā)

生了 3 例嚴重不良事件（SAE），其中 2 例為試驗組，1 例為對照組，研究者判定均與試驗

藥物無關(guān)。無死亡事件發(fā)生。

（3）說明書相關(guān)安全性提示

七蕊胃舒膠囊說明書中不良反應(yīng)描述為：臨床試驗期間受試者用藥后出現(xiàn)月經(jīng)量增

多或減少、肝生化指標升高、腹痛、 腰痛、腸鳴亢進、大便次數(shù)增多、便溏、凝血功能

異常、皮疹瘙癢、尿蛋白異常等。禁忌描述為：孕婦及哺乳期婦女、正在接受透析治療

者、對本品及所含成份過敏者禁用。

七蕊胃舒膠囊是最新獲批的中藥創(chuàng)新藥，經(jīng)歷了目前更為嚴格的中藥說明書修訂要

求，即對藥品的不良反應(yīng)、禁忌、注意事項以及臨床試驗安全性數(shù)據(jù)等有關(guān)藥物安全性

提示內(nèi)容進行了詳細且明確的描述。這與目前很多同類產(chǎn)品相比，在說明書安全性提示

中均未標注“尚不明確”。因此，七蕊胃舒膠囊在指導(dǎo)安全用藥方面具有顯著的優(yōu)勢。

四、七蕊胃舒膠囊經(jīng)濟性分析

1、同類藥物對比

產(chǎn)品名稱 成分

中標價/日

費用（元）

功能主治 用法用量

七蕊胃舒膠囊

三七、枯礬、煅花

蕊石、酒大黃

186.5/62.17

活血化瘀，燥濕止痛。用于輕中度慢性

非萎縮性胃炎伴糜爛濕熱瘀阻證所致的

胃脘疼痛，舌質(zhì)紫黯或瘀斑瘀點、舌苔

黃膩、脈弦澀或弦滑。

口服。一次 4 粒，

一日 2 次，早晚餐

前半小時服用。療

程 4 周。

益氣和胃膠囊

黃芪、丹參、黨

參、黃芩、枳殼、

44.79/14.88

健脾和胃，通絡(luò)止痛。用于慢性非萎縮

性胃炎脾胃虛弱兼胃熱瘀阻證，癥見胃

口服。一次 4 粒，

一日 3 次。

11

白芍、白術(shù)、仙鶴

草、甘草、檀香

脘痞滿脹痛、食少納呆、大便溏薄、體

倦乏力、舌淡苔薄黃、脈細。

三九胃泰膠囊

三叉苦、九里香、

兩面針、木香、黃

芩、茯苓、地黃、

白芍

24.46/8.16

清熱燥濕，行氣活血，柔肝止痛，消炎

止痛，理氣健脾。用于上腹隱痛，飽

脹，反酸，惡心，嘔吐，納減，心口嘈

雜。

口服，一次 2～4

粒，一日 2 次。

三九胃泰顆粒

三叉苦、九里香、

兩面針、木香、黃

芩、茯苓、地黃、

白芍

16.87/3.38

清熱燥濕，行氣活血，柔肝止痛。用于

濕熱內(nèi)蘊、氣滯血瘀所致的胃痛，癥見

脘腹隱痛、飽脹反酸、惡心嘔吐、嘈雜

納減；淺表性胃炎見上述癥候者。

用開水沖服，一次 1

袋，一日 2 次。

蓽鈴胃痛顆粒

蓽澄茄、川楝子、

醋延胡索、酒大

黃、黃連、吳茱

萸、醋香附、香

櫞、佛手、海螵

蛸、煅瓦楞子

46.6/15.54

行氣活血，和胃止痛。用于氣滯血瘀所

致的胃脘痛；慢性胃炎見有上述證候

者。

開水沖服。一次 5

克，一日 3 次。

荊花胃康膠丸 土荊芥、水團花 43.09/8.64

理氣散寒，清熱化瘀。用于寒熱錯雜

證、氣滯血瘀所致的胃脘脹悶疼痛、噯

氣、返酸、嘈雜、口苦；十二指腸潰瘍

見上述證候者。

飯前服，一次 2

粒，一日 3 次；4 周

為一療程，或遵醫(yī)

囑。

七蕊胃舒膠囊的同類藥物均已納入醫(yī)保，但功能主治描述為用于慢性非萎縮性胃炎

的品種僅有一種，七蕊胃舒膠囊也是唯一明確治療慢性非萎縮性胃炎伴糜爛濕熱瘀阻證

所致的胃脘疼痛的中成藥，在服用方面一日兩次相對較為方便。

2、增量成本-效果分析

根據(jù) 2022 年七蕊胃舒膠囊全國主要地區(qū)省級藥采平臺中標價格，得七蕊胃舒膠囊

（24 粒/盒）的最低價格為 186.5 元，即單位劑量價格為 7.77 元/粒；根據(jù) 2020-2022 年

益氣和胃膠囊全國主要地區(qū)省級藥采平臺中標價格，得益氣和胃膠囊（36 粒/盒）的最低

12

價格為 44.79 元，即單位劑量價格為 1.24 元/粒。

基于兩種藥品的使用說明書，將七蕊胃舒膠囊的用法用量定為 4 粒/次、2 次/天，益

氣和胃膠囊的用法用量定為 4 粒/次、3 次/天；以 28 天為一個療程，計算七蕊胃舒膠囊

及益氣和胃膠囊的日均費用、次均費用。

表 1 七蕊胃舒膠囊及益氣和胃膠囊治療慢性非萎縮性胃炎的費用情況（元）

藥品 用法用量 單位制劑

最低價格

銷售單位

最低價格 日均費用 次均費用

七蕊胃舒膠囊 4 粒*2 次/天 7.77 186.5 62.17 1740.76

益氣和胃膠囊 4 粒*3 次/天 1.24 44.79 14.88 416.64

通過中國知網(wǎng)、萬方等查閱相關(guān)文獻，七蕊胃舒膠囊[17]和益氣和胃膠囊[19]治療慢性

非萎縮性胃炎的臨床療效如表 2 所示。

表 2 七蕊胃舒膠囊及益氣和胃膠囊治療慢性非萎縮性胃炎臨床療效

藥品 組別 治療方法 痊愈 顯

效

進

步

無

效

惡

化

總有效率

（%）

七蕊胃舒膠囊 對照組 安慰劑 5 10 23 11 30.61

觀察組 七蕊胃舒膠囊 26 45 22 2 74.74

益氣和胃膠囊

對照組 瑞巴派特片 18 14 6 6 3 68.09

觀察組 益氣和胃膠囊+瑞巴派

特片 30 11 4 1 1 87.23

注:與對照組比較，P<0.05。

結(jié)合七蕊胃舒膠囊和益氣和胃膠囊治療慢性非萎縮性胃炎的臨床療效情況，計算兩

者的成本效果發(fā)現(xiàn)，當七蕊胃舒膠囊降價 44.63%即 4.30 元/粒以下時，相對益氣和胃膠

囊才具有成本效果優(yōu)勢。

表 3 七蕊胃舒膠囊及益氣和胃膠囊治療慢性非萎縮性胃炎的增量成本-效果分析

藥品 增量成本 與對照組的療效差 增量-成本效果比

七蕊胃舒膠囊 1740.67 44.13% 39.45

益氣和胃膠囊 418.04 19.14% 21.77

3、成本-效果分析

根據(jù) 2022 年七蕊胃舒膠囊全國主要地區(qū)省級藥采平臺中標價格，得七蕊胃舒膠囊

（24 粒/盒）的最低價格為 186.5 元，即單位劑量價格為 7.77 元/粒；根據(jù) 2020-2022 年

三九胃泰膠囊全國主要地區(qū)省級藥采平臺中標價格，得三九胃泰膠囊（24 粒/盒）的最低

13

價格為 24.46 元，即單位劑量價格為 1.02 元/粒。

基于兩種藥品的使用說明書，將七蕊胃舒膠囊的用法用量定為 4 粒/次、2 次/天，三

九胃泰膠囊的用法用量定為 4 粒/次、2 次/天；以 28 天為一個療程，計算七蕊胃舒膠囊

及三九胃泰膠囊的日均費用、次均費用。

表 1 七蕊胃舒膠囊及三九胃泰膠囊治療慢性非萎縮性胃炎的費用情況（元）

藥品 用法用量 單位制劑

最低價格

銷售單位

最低價格 日均費用 次均費用

七蕊胃舒膠囊 4 粒*2 次/天 7.77 186.5 62.17 1740.76

三九胃泰膠囊 4 粒*2 次/天 1.02 24.46 8.16 228.48

通過中國知網(wǎng)、萬方等查閱相關(guān)文獻，七蕊胃舒膠囊和三九胃泰膠囊治療慢性非萎

縮性胃炎的臨床療效[18]如表 2 所示。結(jié)合七蕊胃舒膠囊和三九胃泰膠囊治療慢性非萎縮

性胃炎的臨床療效情況，計算兩者的成本效果發(fā)現(xiàn)，當七蕊胃舒膠囊降價 71.96%即 2.17

元/粒以下時，相對三九胃泰膠囊才具有成本效果優(yōu)勢。

表 2 七蕊胃舒膠囊及三九胃泰膠囊治療慢性非萎縮性胃炎臨床療效

藥品 組別 上腹痛消失率 成本-效果 中度上腹痛消失率 成本-效果

七蕊胃舒膠囊 觀察組 78.90% 2206.17 65.0% 26.78

三九胃泰膠囊 對照組 42.20% 540.98 30.4% 7.51

注:與對照組比較，P<0.05。

五、七蕊胃舒膠囊產(chǎn)品總結(jié)

1、創(chuàng)新性

七蕊胃舒膠囊是國內(nèi)首個獲批治療慢性胃炎的中藥 1.1 類創(chuàng)新藥，也是首個明確治

療慢性非萎縮性胃炎伴糜爛濕熱瘀阻證所致的胃脘疼痛的 1.1 類創(chuàng)新藥，研究項目被列

入了國家衛(wèi)生健康委 2018 年度“重大新藥創(chuàng)制”科技重大專項，于 2022 年被正式授予

發(fā)明專利證書 1 項。

2、傳承性

七蕊胃舒膠囊組方源自經(jīng)典名方“硝石礬石散”、“化血丹”加減，組方為三七、枯

礬、煅花蕊石、酒大黃，共奏活血化瘀，燥濕止痛之效，作為院內(nèi)制劑（批準文號：京藥

制 Z20063205）在中國中醫(yī)科學(xué)院廣安門醫(yī)院應(yīng)用了三十余年，用于胃痛中醫(yī)辨證屬痰濕

痰滯證患者療效顯著，安全性高。

14

3、有效性

上市前臨床研究顯示，七蕊胃舒膠囊止痛效果卓越、可顯著改善胃脹、噯氣、泛酸等

中醫(yī)證候，并能顯著改善慢性胃炎患者胃黏膜，促進修復(fù)。

4、安全性

七蕊胃舒膠囊作為院內(nèi)制劑已臨床使用 30 余年，療效與安全性均得到了充分驗證。

同時，產(chǎn)品說明書中對不良反應(yīng)、禁忌、注意事項均進行了詳細且明確的描述，相較同類

藥品的用藥指導(dǎo)更加規(guī)范，用藥更安全。

5、經(jīng)濟性

通過比較功效、適應(yīng)癥等，選用益氣和胃膠囊作為參照藥物時，當七蕊胃舒膠囊價

格為 4.30 元/粒以下，可具有更好的成本效果優(yōu)勢。

6、公平性

七蕊胃舒膠囊是首個明確治療慢性非萎縮性胃炎伴糜爛濕熱瘀阻證所致的胃脘疼痛

的中藥創(chuàng)新藥，可填補該病證的藥物空白，功能主治和臨床適用患者明確，用法用量清

晰，不易形成臨床濫用現(xiàn)象，臨床管理難度低。

六、七蕊胃舒膠囊證明材料（附后）

1、七蕊胃舒膠囊說明書

2、七蕊胃舒膠囊 1.1 類新藥注冊批件

3、七蕊胃舒膠囊臨床倫理批件

4、國家科技重大專項“重大新藥創(chuàng)制”項目

5、七蕊胃舒膠囊發(fā)明專利證書

6、七蕊胃舒膠囊Ⅱ 、Ⅲ 期臨床研究結(jié)果

7、益氣和胃膠囊對照文獻

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【參考文獻】

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瘀滯證隨機、雙盲、多中心平行對照臨床試驗[J/OL].世界中醫(yī)藥:1-5[2022-06-29].

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[19]覃輝、何禮安等.益氣和胃膠囊聯(lián)合瑞巴派特治療慢性非萎縮性胃炎的臨床研究.現(xiàn)代藥物與

臨床, 2019.8.

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基金項目：國家科技重大專項（２０１８ＺＸ０９７３１００４）

作者簡介：韓樹堂 （１９６３０１—２０２１０７），男，博士，主任醫(yī)師，研究方向：消化系統(tǒng)疾病中西醫(yī)臨床研究，Ｅｍａｉｌ：ｈｓｔｊｓｓｚｙｙ＠ｓｉｎａｃｏｍ

七蕊胃舒膠囊對慢性淺表性胃炎伴糜爛濕熱瘀滯證

隨機、雙盲、多中心平行對照臨床試驗

韓樹堂 １

陳 靜１ 田旭東２ 劉啟泉３ 劉鐵軍４ 周正華５

（１江蘇省中醫(yī)院脾胃病科，南京，２１０００４；２甘肅省中醫(yī)院脾胃病科，蘭州，７３００５０；３河北省中醫(yī)院脾胃病科，石家莊，０５００１３；

４長春中醫(yī)藥大學(xué)附屬醫(yī)院肝脾胃科，長春，１３００２１；５天津中醫(yī)藥大學(xué)附屬醫(yī)院脾胃科，天津，３００１９２）

摘要 目的：評價七蕊胃舒膠囊治療慢性淺表性胃炎伴糜爛濕熱瘀滯證的有效性和安全性。方法：選取 ２０１２年 １０月至

２０１５年 ３月江蘇省中醫(yī)院、甘肅省中醫(yī)院、河北省中醫(yī)院、長春中醫(yī)藥大學(xué)附屬醫(yī)院、天津中醫(yī)藥大學(xué)附屬醫(yī)院等 ５家中

心收治的慢性淺表性胃炎伴糜爛濕熱瘀滯證患者 ２３１例作為研究對象。隨機分為觀察組、對照組及安慰劑組。觀察組口

服七蕊胃舒膠囊，對照組患者口服三九胃泰膠囊，安慰劑組患者口服安慰劑，３組均為 ４粒／次，２次／ｄ，餐前半小時服用，

療程 ２８ｄ。觀察用藥后各項癥狀的改變情況和不良反應(yīng)。結(jié)果：觀察組胃脘疼痛消失率高于對照組及安慰劑組，差異有

統(tǒng)計學(xué)意義（Ｐ＜００５）；觀察組胃黏膜糜爛痊愈率顯著高于對照組及安慰劑組，差異有統(tǒng)計學(xué)意義（Ｐ＜００５）；觀察組證

候療效的痊愈率及總顯效率顯著高于對照組及安慰劑組，差異有統(tǒng)計學(xué)意義（Ｐ＜００５）；觀察組幽門螺桿菌根除率高于

對照組及安慰劑組，其中，觀察組與安慰劑組根除率差異有統(tǒng)計學(xué)意義（Ｐ＜００１），而與對照組差異無統(tǒng)計學(xué)意義（Ｐ＞

００５）；觀察組不良反應(yīng)發(fā)生率為 ２６％，對照組無不良反應(yīng)記錄，安慰劑組不良反應(yīng)發(fā)生率為 １８％，３組差異無統(tǒng)計學(xué)意

義（Ｐ＞００５）。結(jié)論：七蕊胃舒膠囊在治療慢性淺表性胃炎伴糜爛濕熱瘀滯證方面臨床療效顯著，安全性較好。

關(guān)鍵詞 七蕊胃舒膠囊；慢性淺表性胃炎；糜爛；濕熱瘀滯；隨機；雙盲；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；

世界中醫(yī)藥　２０２２年 ５月第 １７卷第 １０期 · ５３４１ ·網(wǎng)絡(luò)首發(fā)時間：2022-05-30 16:56:41

網(wǎng)絡(luò)首發(fā)地址：https://kns.cnki.net/kcms/detail/11.5529.R.20220527.1537.012.html

Ｍｕｌｔｉｃｅｎｔｅｒ

中圖分類號：Ｒ２４２；Ｒ５７３３＋１ 文獻標識碼：Ａ ｄｏｉ：１０．３９６９／ｊ．ｉｓｓｎ．１６７３－７２０２．２０２２．１０．０１５

　　慢性淺表性胃炎是由幽門螺桿菌感染、炎癥細

胞浸潤、十二指腸胃反流或藥物毒理反應(yīng)介導(dǎo)的一

系列的胃黏膜慢性炎癥改變，是以腹部脹滿、反酸噯

氣、食欲不振等為主要表現(xiàn)的消化系統(tǒng)疾?。郏保?/p>

。慢

性淺表性胃炎病因復(fù)雜、病程較長，臨床難以徹底治

愈，如未獲得有效治療可發(fā)展為慢性萎縮性胃炎，甚

至少數(shù)患者還存在癌變風(fēng)險［２］

。目前西醫(yī)對其治療

多依靠抑制胃酸分泌、保護胃黏膜、促胃動力等進行

治療，存在周期長、費用高、療效不理想等缺點［３］

。研

究表明，我國人口基數(shù)大，為慢性胃炎大國，在治療該

病過程中，中醫(yī)學(xué)發(fā)揮著積極作用［４］

。中醫(yī)根據(jù)慢性

淺表性胃炎臨床癥狀，將其歸屬于“胃脘痛”“痞滿”

“納呆”等范疇，認為慢性淺表性胃炎多是由于飲食不

節(jié)，過食肥甘厚膩，飲酒，情志不暢等因素導(dǎo)致脾胃失

和，脾失健運，胃失和降，食滯胃脘、氣滯血瘀、濕熱內(nèi)

阻等而產(chǎn)生腹脹、反酸、噯氣、惡心等癥狀［５］

。

七蕊胃舒膠囊由三七、酒大黃、枯礬和煅花蕊石

４味藥組成，具有化瘀除濕、導(dǎo)滯清熱、生肌止痛等

功效。前期實驗研究表明，七蕊胃舒膠囊具有保護

胃黏膜損傷、抑制幽門螺桿菌生長的作用，對慢性淺

表性胃炎伴糜爛濕熱瘀滯證具有較好的治療效果，

并且七蕊胃舒膠囊為中醫(yī)藥制劑，具有不良反應(yīng)少，

安全性高等優(yōu)勢?；诖?，本研究擬采用隨機、雙盲、

平行對照、多中心臨床試驗方法觀察七蕊胃舒膠囊治

療慢性淺表性胃炎伴糜爛濕熱瘀滯證的臨床療效及

安全性，旨在為該藥的臨床應(yīng)用及推廣提供依據(jù)。

１　資料與方法

１１　一般資料 選取 ２０１２年 １０月至 ２０１５年 ３月

江蘇省中醫(yī)院、甘肅省中醫(yī)院、河北省中醫(yī)院、長春

中醫(yī)藥大學(xué)附屬醫(yī)院、天津中醫(yī)藥大學(xué)附屬醫(yī)院等

５家中心收治的慢性淺表性胃炎伴糜爛濕熱瘀滯證

患者 ２３１例作為研究對象。采用隨機、雙盲、平行對

照、多中心臨床試驗方法，利用 ＳＡＳ９２統(tǒng)計軟件包

進行隨機編碼數(shù)字分配，將各中心收治的慢性淺表

性胃炎伴糜爛濕熱瘀滯證患者分為觀察組、對照組

及安慰劑組，３組之間的隨機比例為 ２∶１∶１。共有

２３１例進入全分析集（ＦｕｌｌＡｎａｌｙｓｉｓＳｅｔ，ＦＡＳ）（觀察

組 １１６例、對照組 ５８例、安慰劑組 ５７例）、１８９例進

入符合方案集（ＰｅｒＰｒｏｔｏｃｏｌＳｅｔ，ＰＰＳ）（觀察組 ９５例、

對照組 ４５例、安慰劑組 ４９例）、２３１例進入安全數(shù)

據(jù)集（ＳａｆｅｔｙＳｅｔ，ＳＳ）（觀察組 １１６例、對照組 ５８例、

安慰劑組 ５７例）。觀察組中男 ３３例，女 ６２例，平均

年齡（４２９９±１３７２）歲，平均病程（１５１２±２４５６）

月；安 慰 劑 組 中 男 ２０例，女 ２９例，平 均 年 齡

（４４９２±１１９９）歲，平均病程（２４３１±３９３９）月；

對照組中男 ２１例，女 ２４例，平均年齡 （４４００±

１４０２）歲，平均病程（１２９２±１５６９）月。ＰＰＳ顯示，

３組在年齡、性別、病程、合并疾病、胃脘疼痛、胃脘

痞脹、胃底（糜爛灶）、胃角（糜爛灶）、胃竇（糜爛

灶）、胃底（出血點／斑）、胃體（出血點／斑）、胃角（出

血點／斑）、胃竇（出血點／斑）、噯氣、尿素酶快速試

驗檢測幽門螺桿菌、納呆少食、口苦或口臭或黏、嘈

雜、泛酸癥狀上經(jīng)統(tǒng)計學(xué)分析，差異無統(tǒng)計學(xué)意義

（Ｐ＞００５），具有可比性。本臨床試驗經(jīng)醫(yī)院倫理

委員會批準并與患者簽署知情同意書（倫理審批號：

２０１１ＮＬ０４１０４）。

１２　診斷標準

１２１　慢性淺表性胃炎伴糜爛西醫(yī)診斷標準 參

考中華醫(yī)學(xué)會消化學(xué)分會 ２０００年江西井岡山《全國

慢性胃炎研討會共識意見》《中藥新藥臨床研究指

導(dǎo)原則》制定西醫(yī)診斷標準。１）癥狀：病程遷延；有

不同程度消化不良、厭食及與進食有關(guān)的上腹部疼

痛；可伴有左上腹部輕度壓痛。２）符合慢性淺表性

胃炎伴糜爛內(nèi)鏡診斷標準及病理組織學(xué)診斷標準即

可確診。

１２２　慢性淺表性胃炎伴糜爛濕熱瘀滯證中醫(yī)辨

證標準 依據(jù) １９９５國家中醫(yī)藥管理局《中華人民共

和國中醫(yī)藥行業(yè)標準·中醫(yī)病癥診斷療效標準》

《中藥新藥臨床研究指導(dǎo)原則》“中藥新藥治療慢性

淺表性胃炎伴糜爛的臨床研究指導(dǎo)原則”“中藥新

藥治療胃脘痛的臨床研究指導(dǎo)原則”的標準，中國中

醫(yī)藥學(xué)會中醫(yī)診斷專業(yè)委員會《中醫(yī)病證治法術(shù)

語》（１９９７年），中國中醫(yī)藥學(xué)會脾胃病專業(yè)委員會

《實用中醫(yī)消化病學(xué)》。主癥：１）胃脘疼痛；２）胃脘

痞脹。次癥：１）口苦、口臭或口黏；２）納呆少食；３）

噯氣；４）嘈雜；５）泛酸；６）舌質(zhì)紫暗或有瘀斑瘀點；

舌脈：苔黃膩；脈弦澀或弦滑。具備主癥 １項，次癥 ２

項和相應(yīng)舌脈即可診斷。

１３　納入標準?。保┓下詼\表性胃炎伴糜爛的

西醫(yī)診斷標準；２）符合中醫(yī)濕熱瘀滯證辨證標準；３）

年齡在 １８～６５歲者，性別不限；４）知情同意，志愿受

試。獲得知情同意書過程應(yīng)符合藥品臨床試驗管理

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

規(guī)范規(guī)定。

１４　排除標準?。保┞晕s性胃炎；其他繼發(fā)性胃

炎；合并有胃、十二腸潰瘍，胃黏膜有重度異型增生

或病理診斷疑有惡變者；２）本次發(fā)病后 １周內(nèi)已使

用相關(guān)治療藥物；３）妊娠期、哺乳期婦女；４）具有嚴

重的原發(fā)性心、肝、肺、腎、血液或影響其生存的嚴重

疾病，如腫瘤或艾滋?。荒I功能異常；谷丙轉(zhuǎn)氨酶

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

常值上限）；血白細胞 ＜３０×１０９／Ｌ；５）由于精神和

行為障礙不能給予充分知情同意者；６）懷疑或確有

乙醇、藥物濫用病史；７）根據(jù)研究者的判斷，具有降

低入組可能性或使入組復(fù)雜化的其他病變，如工作

環(huán)境經(jīng)常變動等易造成失訪的情況；８）過敏體質(zhì)，如

對 ２種或以上藥物或食物過敏史者；或已知對本藥

成分過敏者；９）正在參加其他藥物臨床試驗的患者。

１５　脫落與剔除標準 未完成本方案所規(guī)定的療

程及觀察周期。資料統(tǒng)計分析前，由統(tǒng)計人員及主

要研究者討論判斷病例是否剔除。

１６　治療方法 按每位受試者入組先后順序和藥

物編號順序逐例發(fā)藥。觀察組予以七蕊胃舒膠囊

（武漢健民藥業(yè)集團股份有限公司，批號：１２０５０１）口

服，４粒／次，２次／ｄ，連續(xù)服藥 ４周。觀察組予以三

九胃泰膠囊（華潤三九醫(yī)藥股份有限公司，批號：

１２０１００５Ｈ）口服，４粒／次，２次／ｄ，連續(xù)服藥 ４周。

安慰劑組予以安慰劑（外觀與七蕊胃舒膠囊、三九胃

泰膠囊一致，符合安慰劑制備要求，武漢健民藥業(yè)集

團股份有限公司，批號：１３０７０１）口服，４粒／次，２次／

ｄ，連續(xù)服藥 ４周。

１７　觀察指標?。保┪鸽涮弁?、胃脘痞脹消失率。２）

胃黏膜糜爛改善情況，胃鏡檢查，痊愈：糜爛消失，顯

效：糜爛分級由 ３級降為 １級，有效：糜爛分級降低 １

個等級，即由 ３級降為 ２級或由 ２級降為 １級，無

效：糜爛無好轉(zhuǎn)，甚或加重。３）納呆少食、口苦或口

臭或黏、嘈雜、泛酸證候療效。４）幽門螺桿菌根除

率，根除：治療后幽門螺桿菌 Ｃ１３或 Ｃ１４檢測由陽性

轉(zhuǎn)為陰性；未根除：治療后幽門螺桿菌 Ｃ１３或 Ｃ１４檢

測仍為陽性。５）記錄不良反應(yīng)。

１８　療效判定標準 療效采用尼莫地平法計算，公

式為 ＝（療前證候積分 －療后證候積分）／療前證候

積分。臨床痊愈：癥狀、體征消失或基本消失，療效

指數(shù)≥９５％。顯效：癥狀、體征明顯改善，７０％≤療

效指數(shù) ＜９５％。有效：癥狀、體征好轉(zhuǎn)，３０％≤療效

指數(shù) ＜７０％。無效：癥狀、體征無明顯改善，甚或加

重，療效指數(shù) ＜３０％?！芭R床痊愈、顯效”合并計算總

有效率。

１9 統(tǒng)計學(xué)方法 采用 ＳＡＳ９２統(tǒng)計軟件進行數(shù)據(jù)

分析。除優(yōu)效性檢驗的統(tǒng)計檢驗均采用雙側(cè)檢驗，

Ｐ≤００５者將被認為所檢驗的判別有統(tǒng)計學(xué)意義。

對胃脘疼痛、胃脘痞脹消失率及幽門螺桿菌根除率

采用 χ

２檢驗；對胃鏡下胃黏膜糜爛總體療效、中醫(yī)

證候療效采用 χ

２ 檢驗。對不良事件采用 χ

２ 檢驗／

Ｆｉｓｈｅｒ法檢驗。

２　結(jié)果

２１　各組患者治療后胃脘疼痛消失率比較 觀察

組胃脘疼痛消失率最高，安慰劑組的消失率最低，３

組消失率分別為 ７８９％、４２２％、２８６％；觀察組胃

脘疼痛消失率顯著高于對照組及安慰劑組，且差異

有統(tǒng)計學(xué)意義（Ｐ＜００５）；對照組胃脘疼痛消失率

雖高于安慰劑組，但差異無統(tǒng)計學(xué)意義（Ｐ＞００５）。

見表 １。

表 １　各組患者胃脘疼痛消失率比較［例（％）］

組別 消失 未消失

觀察組（ｎ＝９５） ７５（７８９）△ ２０（２１１）

對照組（ｎ＝４５） １９（４２２） ２６（５７８）

安慰劑組（ｎ＝４９） １４（２８６） ３５（７１４）

　　注：與對照組比較， Ｐ＜００５；與安慰劑組比較，△ Ｐ＜００５

２２　各組患者治療后胃脘痞脹消失率比較 觀察

組胃 脘 痞 脹 消 失 率 （６５３％）略 低 于 對 照 組

（６８９％），差異無統(tǒng)計學(xué)意義（Ｐ＞００５）；安慰劑組

胃脘痞脹消失率最低，為 ５３１％，與其他 ２組之間的

差異同樣無統(tǒng)計學(xué)意義（Ｐ＞００５）。見表 ２。

表 ２　各組患者胃脘痞脹消失率比較［例（％）］

組別 消失 未消失

觀察組（ｎ＝９５） ６２（６５３） ３３（３４７）

對照組（ｎ＝４５） ３１（６８９） １４（３１１）

安慰劑組（ｎ＝４９） ２６（５３１） ２３（４６９）

２３　各組患者治療后胃黏膜糜爛療效比較 觀察

組胃黏膜糜爛痊愈率最高，安慰劑組的痊愈率最低，

３組痊愈率分別為 ６５３％、４６７％、３０６％；觀察組

胃黏膜糜爛痊愈率顯著高于對照組及安慰劑組，且

差異有統(tǒng)計學(xué)意義（Ｐ＜００５）；對照組胃黏膜糜爛

痊愈率雖高于安慰劑組，但差異無統(tǒng)計學(xué)意義（Ｐ＞

００５）。見表 ３。

表 ３　各組患者胃黏膜糜爛療效比較［例（％）］

組別 痊愈 顯效 進步 無效

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

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

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

　　注：與對照組比較， Ｐ＜００５；與安慰劑組比較，△ Ｐ＜００５

世界中醫(yī)藥　２０２２年 ５月第 １７卷第 １０期 · ７３４１ ·

表 ４　各組患者證候療效分析

組別 痊愈［例（％）］ 顯效［例（％）］ 進步［例（％）］ 無效［例（％）］ 有效率（％）

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

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

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

　　注：與對照組比較， Ｐ＜００５；與安慰劑組比較，△ Ｐ＜００５， Ｐ＜００１

２４　各組患者治療后證候療效比較 觀察組證候

療效的痊愈率最高，為 ２７３７％顯著高于對照組及

安慰劑組，且差異有統(tǒng)計學(xué)意義（Ｐ＜００５）；對照組

證候療效的治愈率高于安慰劑組，但差異無統(tǒng)計學(xué)

意義（Ｐ＞００５）；觀察組有效率顯著高于對照組及

安慰組，差異有統(tǒng)計學(xué)意義（Ｐ＜００５），同時，對照

組有效率也高于安慰劑組，差異有統(tǒng)計學(xué)意義（Ｐ＜

００１）。見表 ４。

２５　各組患者治療后幽門螺桿菌根除率比較 觀

察組幽門螺桿菌根除率為 ５２７％，高于對照組及安

慰劑組，其中，觀察組與安慰劑組間根除率差異有統(tǒng)

計學(xué)意義（Ｐ＜００１），而觀察組幽門螺桿菌根除率

雖高于對照組，但差異無統(tǒng)計學(xué)意義（Ｐ＞００５）；同

時，對照組幽門螺桿菌根除率也高于安慰劑組，但差

異也無統(tǒng)計學(xué)意義（Ｐ＞００５）。見表 ５。

表 ５　各組患者幽門螺桿菌根除率比較［例（％）］

組別 根除 未根除 合計（缺失）

觀察組（ｎ＝９５） ２９（５２７） ２６（４７３） ５５（４０）

對照組（ｎ＝４５） ９（３４６） １７（６５４） ２６（１９）

安慰劑組（ｎ＝４９） ７（２２６） ２４（７７４） ３１（１８）

　　注：與安慰劑組比較， Ｐ＜００１

２６　各組不良事件比較 觀察組有 ３例發(fā)生了與

研究藥物有關(guān)的不良反應(yīng)，其中 ２例表現(xiàn)為月經(jīng)量

增多（１例可能與試驗用藥有關(guān)，另 １例與試驗藥物

關(guān)系為可疑）；１例表現(xiàn)為肝功能改變（與試驗用藥

關(guān)系可疑）；安慰劑組有 １例發(fā)生不良事件（與試驗

藥不可能有關(guān)系）；觀察組、對照組及安慰劑組 ３組

不良反應(yīng)差異均無統(tǒng)計學(xué)意義（Ｐ＞００５）。見表 ６。

表 ６　各組不良反應(yīng)比較［例（％）］

組別 有 無

觀察組（ｎ＝１１６） ３（２６） １１３（９７４）

對照組（ｎ＝５８） ０（００） ５８（１０００）

安慰劑組（ｎ＝５７） １（１８） ５６（９８２）

３　討論

目前，隨著經(jīng)濟的飛速發(fā)展，食品種類豐富，人

們飲食習(xí)慣、結(jié)構(gòu)及生活方式、節(jié)奏的變化，消化系

統(tǒng)疾病的發(fā)病風(fēng)險越來越高［６］

。消化系統(tǒng)疾病主

要包括慢性非萎縮性胃炎、慢性萎縮性胃炎、急性胃

炎、消化道潰瘍、功能性消化不良等疾病，是臨床常

見病、多發(fā)病。據(jù)調(diào)查顯示，我國在接受胃鏡檢查的

患者中，慢性胃炎約占 ９０％［７］

，并且根據(jù)一項橫斷

面調(diào)查顯示，在各型慢性胃炎中，慢性非萎縮性胃炎

的內(nèi)鏡診斷率約為 ４９４％，慢性非萎縮性胃炎伴糜

爛的內(nèi)鏡診斷率高達 ４２３％，故對于慢性非萎縮性

胃炎，糜爛是其高發(fā)伴隨狀態(tài)［８］

。研究顯示，慢性

非萎縮性胃炎伴糜爛癥狀易反復(fù)發(fā)作，可導(dǎo)致消化

性潰瘍、上消化道出血、癌前病變，甚至胃癌等，不僅

嚴重影響了患者的生命質(zhì)量，而且也加重了患者的

心理負擔與經(jīng)濟負擔［９］

。

中醫(yī)學(xué)從整體出發(fā)，辨證施治，對于慢性非萎縮

性胃炎的治療，不僅在一定程度上彌補了現(xiàn)代醫(yī)學(xué)

治療的不足，而且在緩解臨床癥狀、延緩病情進展方

面具有一定優(yōu)勢，易被患者接受［１０］

。中醫(yī)認為本病

的病因主要為脾胃虛弱、情志不暢、飲食不節(jié)等，病

變部位在脾胃，多夾郁熱、絡(luò)瘀、瘀熱常合濕濁，虛實

夾雜尤為常見，故多采用清熱涼血、化瘀散結(jié)、化濕

濁、斂瘍生肌等治法［１１］

。

七蕊胃舒膠囊在臨床上用于治療慢性淺表性胃

炎伴糜爛濕熱瘀滯證，功效化瘀除濕、導(dǎo)滯清熱、生

肌止痛，具有中和胃酸，保護胃黏膜及促進潰瘍愈合

等作用。七蕊胃舒膠囊由三七、酒大黃、枯礬和煅花

蕊石四味藥組成，方中三七為君藥，其性味甘、微苦，

溫，為理血要藥，具有止血不留瘀，化瘀不傷正的作

用。現(xiàn)代藥理研究顯示，三七的主要有效成分包括

三七總皂苷、三七素、黃酮、揮發(fā)油及微量元素等，具

有止血、活血、抗血栓、抗炎、鎮(zhèn)痛等作用，其中活血、

止血之效可針對慢性淺表性胃炎伴糜爛濕熱瘀滯證

的“瘀、毒”之邪發(fā)揮活血解毒之效；枯礬性味酸澀、

寒，為方中臣藥，具有消痰，燥濕，止瀉，解毒，殺蟲的

功效，臨床上對其多采取煅用，具有收斂潰瘍創(chuàng)面、

生肌利水的功效，在治療慢性淺表性胃炎伴糜爛中

發(fā)揮收斂糜爛的胃黏膜，促進胃黏膜修復(fù)的功效。

花蕊石性味酸澀、平，可化瘀止血，并能制酸止痛，為

佐藥?！侗静菥V目》記載花蕊石：“治一切失血損傷，

其功專于止血，能使血化為水?！被ㄈ锸饕瘜W(xué)成

分包括碳酸鈣與氧化鈣，可有效中和胃酸，保護胃黏

· ８３４１ · ＷＯＲＬＤＣＨＩＮＥＳＥＭＥＤＩＣＩＮＥ?。停幔玻埃玻?，Ｖｏｌ．１７，Ｎｏ．１０

膜。大黃為方中使藥，味苦寒，主清熱瀉火、瀉下攻

積、逐淤通經(jīng)、涼血解毒等，其主要化學(xué)成分為大黃

素、大黃酸、大黃酚、蘆薈大黃素、大黃素甲醚等，具

有抑菌、抗病毒、免疫調(diào)節(jié)、抗腫瘤等作用［１２］

。實驗

研究顯示，大黃可提高胃腸黏膜內(nèi)的 ｐＨ值，改善胃

黏膜血流灌注，糾正胃腸缺血缺氧狀態(tài)，并且大黃還

可清除組織及血漿內(nèi)的炎癥介質(zhì)，降低胃黏膜的通

透性，防治胃腸感染［１３１４］

。此外，大黃中的主要有

效成分大黃素可引起幽門螺桿菌 ＤＮＡ損傷，影響幽

門螺桿菌芳胺乙酰轉(zhuǎn)移酶的活性，從而發(fā)揮抗幽門

螺桿菌的作用［１５］

。方中三七活血行血；白礬與花蕊

石同用，收斂燥濕，促進胃黏膜修復(fù)；大黃通腑瀉熱，

解毒活血，諸藥配伍使用，可活血化瘀，中和胃酸、保

護胃黏膜，有效治療慢性非萎縮性胃炎伴糜爛。

本研究結(jié)果表明，觀察組胃脘疼痛消失率高于

對照組及陽性藥物組，且差異有統(tǒng)計學(xué)意義（Ｐ＜

００５）。觀察組胃脘痞脹消失率與對照組接近，觀

察組及對照組與安慰劑組胃脘痞脹消失率之間的差

異無統(tǒng)計學(xué)意義（Ｐ＞００５），但都高于安慰劑組的

５３１％。同時，觀察組患者胃黏膜糜爛療效、證候療

效及幽門螺桿菌根除率均顯著優(yōu)于對照組及安慰劑

組，其中與安慰劑組差異有統(tǒng)計學(xué)意義（Ｐ＜００５）。

提示七蕊胃舒膠囊對慢性淺表性胃炎伴糜爛濕熱瘀

滯證患者的胃脘疼痛、胃脘痞脹、胃部糜爛、納呆少

食、口苦或口臭或黏、嘈雜、泛酸及幽門螺旋桿菌感

染具有良好的治療效果，且改善效果優(yōu)于三九胃泰

膠囊。此外，研究結(jié)果也表明觀察組、對照組及安慰

劑組 ３組不良反應(yīng)發(fā)生率低，且差異均無統(tǒng)計學(xué)意

義（Ｐ＞００５），提示七蕊胃舒膠囊治療慢性淺表性

胃炎伴糜爛濕熱瘀滯證具有良好的安全性。

綜上所述，七蕊胃舒膠囊在治療慢性淺表性胃

炎伴糜爛濕熱瘀滯證方面臨床療效顯著，尤其是在

改善胃脘疼痛、胃黏膜糜爛、中醫(yī)證候及幽門螺旋桿

菌感染等方面，療效優(yōu)于對照藥三九胃泰膠囊，并且

安全性較好，值得臨床推廣使用。

參考文獻

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患者外周血胃腸激素、Ｔ淋巴細胞亞群、ＩＬ８、ＩＬ３２、ＭＣＰ１的影

響［Ｊ］．中藥材，２０２０，４３（１１）：２８１３２８１７．

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３０６９３０７２．

［４］徐藝峰，王憶勤，郝一鳴．慢性胃炎濕熱證形成及中藥治療機制

研究進展［Ｊ］．世界科學(xué)技術(shù)中醫(yī)藥現(xiàn)代化，２０２１，２３（３）：６９９

７０４．

［５］紀萬里，王婷婷，安轈，等．基于定量蛋白質(zhì)組學(xué)技術(shù)探究半夏瀉

心湯對慢性胃炎大鼠影響的作用機制［Ｊ］．中國實驗方劑學(xué)雜

志，２０２１，２７（９）：１８．

［６］元剛，吳海燕，王春桃，等．消化科住院患者用藥習(xí)慣調(diào)查與分析

［Ｊ］．今日藥學(xué)，２０１１，２１（９）：５７３５７５．

［７］ＪｉａｎｇＪＸ，ＬｉｕＱ，ＭａｏＸＹ，ｅｔａｌ．Ｄｏｗｎｗａｒｄｔｒｅｎｄｉｎｔｈｅｐｒｅｖａｌｅｎｃｅｏｆ

Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉｉｎｆｅｃｔｉｏｎｓａｎｄｃｏｒｒｅｓｐｏｎｄｉｎｇｆｒｅｑｕｅｎｔｕｐｐｅｒｇａｓ

ｔｒｏｉｎｔｅｓｔｉｎａｌｄｉｓｅａｓｅｓｐｒｏｆｉｌｅｃｈａｎｇｅｓｉｎＳｏｕｔｈｅａｓｔｅｒｎＣｈｉｎａｂｅｔｗｅｅｎ

２００３ａｎｄ２０１２［Ｊ］．Ｓｐｒｉｎｇｅｒｐｌｕｓ，２０１６，５（１）：１６０１．

［８］ＤｕＹ，ＢａｉＹ，ＸｉｅＰ，ｅｔａｌ．ＣｈｒｏｎｉｃｇａｓｔｒｉｔｉｓｉｎＣｈｉｎａ：ａｎａｔｉｏｎａｌｍｕｌｔｉ

ｃｅｎｔｅｒｓｕｒｖｅｙ［Ｊ］．ＢＭＣＧａｓｔｒｏｅｎｔｅｒｏｌ，２０１４，１４：２１．

［９］吳皓萌，黃紹剛，王鳳云，等．基于胃微環(huán)境探討中醫(yī)藥防治胃癌

前病變的機制［Ｊ］．中國實驗方劑學(xué)雜志，２０２１，２７（１６）：２４５２５０．

［１０］唐旭東，王鳳云，張聲生，等．消化系統(tǒng)常見病慢性非萎縮性胃

炎中醫(yī)診療指南（基層醫(yī)生版）［Ｊ］．中華中醫(yī)藥雜志，２０１９，３４

（８）：３６１３３６１８．

［１１］王濤，王萍，遲偉．白長川從胃滯虛熱論治慢性非萎縮性胃炎伴

糜爛［Ｊ］．遼寧中醫(yī)雜志，２０１９，４６（４）：６９３６９５．

［１２］張橋，陳艷琰，樂世俊，等．大黃炮制的歷史沿革及對化學(xué)成分、

傳統(tǒng)藥理作用影響的研究進展［Ｊ］．中國中藥雜志，２０２１，４６

（３）：５３９５５１．

［１３］原鳳蕉，李曉雪，尚海，李凌宇，宋艷玲，鄒忠梅．蘆薈大黃素吲

哚偶聯(lián)物的合成及抗腫瘤活性研究［Ｊ］．中草藥，２０２１，５２（０８）：

２２１７２２２５．

［１４］樊君，喬迪，陳廣．大黃素對 ＬＰＳ誘導(dǎo)的心肌細胞炎癥反應(yīng)和細

胞凋亡的影響及機制［Ｊ］．中成藥，２０２１，４３（３）：６３０６３５．

［１５］吳明慧，黃衍強，黃贊松，等．黃連素、大黃素、五味子及黃芩苷

對幽門螺桿菌多重耐藥株的體外抑菌作用［Ｊ］．世界華人消化

雜志，２０１３，２１（３０）：３２４７３２５１．

（２０２２－０３－１９收稿 本文編輯：吳珊）

世界中醫(yī)藥?。玻埃玻材?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,

H.-F. Chen et al.

Journal of Ethnopharmacology 294 (2022) 115341

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.

H.-F. Chen et al.

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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.

H.-F. Chen et al.

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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.

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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

中藥七蕊胃舒膠囊治療慢性非萎縮性胃炎的療效和安全性：

一項多中心、雙盲、隨機對照臨床試驗

陳華芳 a，*，鞏陽 b，黃志軍 c，趙剛 c，陳志敏 d，曾耀明 e，李慧臻 f，胡運蓮 g

a溫州醫(yī)科大學(xué)第一附屬醫(yī)院，325000，中國浙江

b解放軍北部戰(zhàn)區(qū)總醫(yī)院，110016，中國遼寧

c健民集團兒童藥物研究所，430050，中國湖北

d寧波市中醫(yī)院，315010，中國浙江

e溫州市中醫(yī)院，，郵編：325000，中國浙江

f天津醫(yī)科大學(xué)第二附屬醫(yī)院，郵編：300150，中國天津

g湖北省中醫(yī)院，郵編：430060，中國湖北

關(guān)鍵詞：隨機對照試驗 慢性非萎縮性胃炎 濕熱瘀阻證 中醫(yī)學(xué)

摘要：

民族藥理學(xué)關(guān)聯(lián)：七蕊胃舒膠囊是由中國中醫(yī)科學(xué)院廣安門醫(yī)院一位經(jīng)驗豐富的醫(yī)生開出的中

藥組方制成的中藥制劑。它已經(jīng)在臨床上使用了 30 多年。腹痛、腹脹、惡心是慢性非萎縮性

胃炎伴糜爛濕熱瘀阻證的常見癥狀，而這種中藥制劑已被用于這些癥狀的臨床治療。

研究目的：驗證七蕊胃舒膠囊治療慢性非萎縮性胃炎伴濕熱瘀阻證的臨床療效和安全性。

材料與方法：本研究為多中心、隨機、雙盲臨床試驗，以陽性中藥三九胃泰膠囊為對照，進行

主要療效優(yōu)勢試驗。477 例經(jīng)胃鏡和病理活檢確診的慢性非萎縮性胃炎糜爛患者，按 3:1 的比

例隨機分為七蕊胃舒膠囊組和三九胃泰組。在試驗期間，受試者需要完成 28 天的藥物治療。

主要結(jié)果是從基線檢查到 4 周時上腹部疼痛的消失率。在基線檢查、治療 1 周、2 周和 4 周以

及隨訪 8 周和 16 周時，評估上腹痛和中醫(yī)癥狀評分；在基線檢查和治療 4 周后評估胃鏡檢查、

組織病理學(xué)和幽門螺桿菌試驗。安全性評估包括血常規(guī)、肝腎功能、實驗室檢查凝血和心電圖

（ECG）。