Review of the Regulations for Clinical Research in Herbal Medicines in USA

In 2012,USA Food and Drug Administration（FDA） approved 39 new drugs,however,there are only two botanical drugs（one topical and one oral）approved by FDA since the publication of the FDA＇s industry guidelines for the botanical drug product in June 2004.The approval shows the Western guideline can be used for herbal medicines,authors investigate current regulation on herbal medicine clinical research,identify challenges conducting clinical trials,and seek to produce some guidance for potential investigators and sponsors considering a clinical trial in this area.Key words were formulated for searching on Medline and FDA website to locate relevant regulations for clinical research in herbal medicines to understand current environment for herbal medicine usage and examine the barriers affecting herbal medicine in clinical trials.Authors critically explore case study of the 1st FDA approved botanical drugs,Veregen（sinecatechins）,green tea leaves extract,a topical cream for perianal and genital condyloma.In consideration of current regulation environment in USA,based on the findings and analysis through the literature review and Veregen case study,authors produce and propose a Checklist for New Drug Application of Herbal Medicines for potential investigators and sponsors considerina in a herbal medicine clinical trial.     

Chinese Medicine as Complementary Therapy for Female Infertility

Chinese medicine (CM) has been used in clinical treatment for thousands of years in China, Japan, Korea, and other countries. CM is at present attracting many attentions around the world for reproductive health care and disease prevention, including treatment of female infertility. This review focuses on the CM treatment for female infertility patients, and supplies a summary on the efficacy, safety, and mechanism of some Chinese herbal medicines, herbal medicine-derived active compounds, and acupuncture. A large number of researches have reported that CM could alleviate or even cure female infertility by regulating hormone, improving reproductive outcome of in vivo fertilization, affecting embryonic implantation, curing polycystic ovarian syndrome, endometriosis, pelvic inflammatory disease, relieving mental stress, and regulating immune system. Meanwhile, a few studies claimed that there was little adverse reaction of CM in randomized controlled trials. However, up to present there is a lack of adequate evidences with molecular mechanistic researches and randomized controlled trials to prove the CM as an effective and safe treatment for infertility. Thus, utility of CM as a complementary medicine will be a feasible method to improve the outcome of female infertility treatment.     

传统草药治疗脑缺血的疗效：潜在的血管保护作用

Although many agents for acute ischemic stroke treatment have been developed from extensive preclinical studies, most have failed in clinical trials. As a result, researchers are seeking other methods or agents based on previous studies. Among the various prospective approaches, vascular protection might be the key for development of therapeutic agents for stroke and for improvements in the efficacy and safety of conventional therapies. Traditional medicines in Asian countries are based on clinical experiences and literature accumulated over thousands of years. To date, many studies have used traditional herbal medicines to prove or develop new agents based on stroke treatments mentioned in traditional medicinal theory or other clinical data. In the current review, we describe the vascular factors related to ischemic brain damage and the herbal medicines that impact these factors, including Salviae Miltiorrhizae Radix, Notoginseng Radix, and Curcumae Rhizoma, based on scientific reports and traditional medical theory. Further, we point out the problems associated with herbal medicines in stroke research and propose better methodologies to address these problems.     

中药对照软骨保护剂改善膝骨关节炎功能活动的系统评价

[目的]系统评价中药对照软骨保护剂改善膝骨关节炎的功能活动及药物安全性。[方法]检索中国知识资源总库(Chinese National KnowledgeInfrastructure, CNKI)、维普期刊数据库(VIP Journal Database,VIP)、万方数据知识服务平台(Wan-fang Data Knowledge Service Platform,Wan-Fang)、中国生物医学文献数据库(China Biology Medicine, CBM)中有关中药与软骨保护剂的随机和半随机对照临床试验,检索时限至2018年6月30日。由2名研究者依据纳入排除标准独立筛选文献、提取数据、并行文献质量评价,运用RevMan5.3软件进行统计分析。[结果]共纳入9项研究,合计689例膝骨性关节炎患者。6项研究因较大异质性仅采用描述性分析,2项研究Meta分析结果显示口服中药汤剂膝关节功能活动评分与软骨保护剂比较有统计学差异[SMD=-0.33,95%CI(-0.62,-0.33), P0.05]。[结论]口服中药汤剂在约3个月时对膝关节功能活动的改善优于软骨保护剂,但基于现有研究缺陷,结论尚需高质量的随机对照试验予以证实。     

中草药治疗银屑病致药物性肝病34例临床分析

目的分析中草药治疗银屑病所致药物性肝病的临床特点,提高对药物性肝病的认识.方法回顾性总结我院收治的34例中草药治疗银屑病所致药物性肝病患者临床资料,对损肝药物、临床特点、并发症及预后等方面进行分析.结果34例患者临床主要症状多表现为乏力、纳差、恶心、尿液发黄;实验室检查可有谷丙转氨酶(ALT)、血清总胆红素(TB)升高、凝血酶原活动度降低表现.所致药物性肝病以药物性肝炎常见,占67.6%,肝硬化占26.5%,肝衰竭占5.9%,常见并发症有腹水、电解质紊乱、原发性腹膜炎、胸腔积液、肝性脑病、上消化道出血.本组患者死亡率为2.9%.结论中草药治疗银屑病所致药物性肝病临床并不少见,长期服用可致肝硬化,重者可导致肝衰竭甚至死亡,用药过程中应密切监测肝功能.     

中草药临床研究的评价

补充替代医学正被广泛应用,并呈现出良好的增长趋势。随着寻求补充替代医学疗法的人口比例的增长,无论是补充替代医学被单独使用,还是与传统的对抗疗法联合应用,对补充替代医学临床报告质量的研究变得日益迫切。大部分这种质量研究是针对那些主要目的在于为临床医师提供参考的临床研究报告,我们发现,在解释临床研究的结果及其意义时,人们不得不面对其方法学质量低劣的问题。如何解决这个问题,将是我们面临的巨大挑战。临床医师要有效地利用这些科学研究的文献,就必须熟悉循证医学的基本原则。本文的目的在于向临床医师介绍临床研究评价的概念,使他们在阅读研究论文时能带着评判的眼光,以便更好地评价论文中的研究结果,并将其合理地运用到自己的日常医疗实践中去。本文主要讨论了以下六个方面的问题:(1)循证医学的基本原理;(2)临床研究的类型;(3)证据的分级;(4)应用临床试验报告统一标准评价随机对照试验报告的质量;(5)随机对照试验方法学质量的评分;(6)中草药临床研究质量评价的有关问题。     

Why don't we use vitamin E in dermatology?

OBJECTIVE: To review the possible uses of topical and systemic tocopherols as therapy for skin conditions in light of the widespread use of vitamin E by patients. DATA SOURCES: Index Medicus was searched for articles published from 1922 (when vitamin E was discovered) to 1966 (the beginning of MEDLINE). MEDLINE was searched for articles in English and French on vitamin E or tocopherol in relation to dermatology. Additional original articles were identified from the reference lists of the review articles. STUDY SELECTION: Only well-designed controlled studies were accepted; anecdotes and open studies are cited for completeness and as direction for future research. DATA SYNTHESIS: There was some weak or conflicting evidence that vitamin E is of value in yellow nail syndrome, vibration disease, epidermolysis bullosa, cancer prevention, claudication, cutaneous ulcers, and collagen synthesis and wound healing. It was of no use in atopic dermatitis, dermatitis herpetiformis, psoriasis, subcorneal pustular dermatosis, porphyrias and skin damage induced by ultraviolet light. CONCLUSIONS: After 44 years of research there is still scant proof of vitamin E's effectiveness in treating certain dermatologic conditions. Further research in well-designed controlled trials is needed to clarify vitamin E's role.     

Complementary and alternative medicine in the treatment of menopausal symptoms

A large number of women will pass through menopause each year. Women in menopausal transition experience a variety of menopausal symptoms. Although hormonal therapy remains the most effective treatment,side effects have been reported by several large studies.An increased number of women seek the use of complementary and alternative medicine(CAM) for treating menopausal symptoms.This review analyzes the evidence from systematic reviews,randomized controlled trials and epidemiological studies of using herbal medicine(Black cohosh, Dong quai,St John’s wart,Hops,Wild yam,Ginseng,and evening primrose oil) and acupuncture for the treatment of menopausal symptoms.Evidence supporting the efficacy and safety of most CAM for relief of menopausal symptoms are limited. Future larger and better controlled studies testing the effectiveness of these treatments are needed.     

Chinese herbal medicine in the treatment of nonalcoholic fatty liver disease

Chinese herbal medicine has developed new therapies for nonalcoholic fatty liver disease (NAFLD) based on its unique theory system and substantial herb remedies.In this review,21 traditional Chinese herbs were introduced for their potential benefit in the treatment of NAFLD.Majority of them are evaluated by experimental studies and few by multicenter clinical trials.Herbal monomers as berberine and resveratrol,extracts from Polygonum hypoleucum Ohwi,and Artemisia sacrorum Ledeb.,and formulae including Yinchenhao Decoction(茵陈蒿汤,YCHD),Qushi Huayu Decoction(祛温化瘀汤,QSHYD),and Danning Tablet (胆宁片) were discussed in detail on their therapeutic potentials.Most of these herbal medicines were proved to improve biochemical and histological changes of NAFLD both in vitro and in vivo.Also,their therapeutic activities were associated with inhibiting lipid accumulation through adenosine monophosphate-activated protein kinase activation or upregulating low-density lipoprotein receptor(LDLR) expression,alleviating lipid peroxidation,and reducing the production of inflammatory cytokines.Although the efficacy and safety of these herbal medicines needed to be evaluated in multicenter large-scale clinical trials,Chinese medicine is promising and effective for preventing and treating NAFLD disease.     

中医药治疗艾滋病研究进展

艾滋病在我国已进入快速传播期，积极开展具有我国特色的中医药治疗艾滋病研究具有重要意义。中医认为艾滋病的病因为邪毒外侵和肾精亏损；病机为脏腑虚损和气血津液失常；临床和实验研究已发现一批治疗艾滋病有效的单味药和复方，作用机理主要是抑制艾滋病病毒，调整免疫功能和控制机会性感染；中医药治疗艾滋病研究还存在一些问题并提出相关对策。     

Herbal Medicine in Ischemic Stroke: Challenges and Prospective

Herbal medicines, mainly of plant source, are invaluable source for the discovery of new therapeutic agents for all sorts of human ailments. The complex pathogenesis of stroke and multifactorial effect of herbal medicine and their active constituents may suggest the promising future of natural medicine for stroke treatment. Anti-oxidant, anti-inflammatory, anti-apoptotic, neuroprotective and vascular protective effect of herbal medicines are believed to be efficacious in stroke treatment. Herbs typically have fewer reported side effects than allopathic medicine, and may be safer to use over longer period of time. Herbal medicines are believed to be more effective for the longstanding health complaints, such as stroke. Several medicinal plants and their active constituents show the promising results in laboratory research. However failure in transformation of laboratory animal research to the clinical trials has created huge challenge for the use of herbal medicine in stroke. Until and unless scientifically comprehensive evidence of the efficacy and safety of herbal medicine in ischemic stroke patients is available, efforts should be made to continue implementing treatment strategies of proven effectiveness. More consideration should be paid to natural compounds that can have extensive therapeutic time windows, perfect pharmacological targets with few side effects. Herbal medicine has excellent prospective for the treatment of ischemic stroke, but a lot of effort should be invested to transform the success of animal research to human use.     

新型糖皮质激素在炎症性肠病治疗中有效性和安全性的研究现状

炎症性肠病包括溃疡性结肠炎和克罗恩病,全世界约有2 500 000人患有此病.其病因可能是基因易感人群对肠道菌群的免疫应答失调.传统糖皮质激素能有效诱导活动期疾病缓解,但同时伴有诸多全身副作用.新型糖皮质激素如布地奈德和倍氯米松,粘膜吸收、灭活迅速,起效快,抗炎作用强且全身副作用少.这些新型制剂口服后被小肠的吸收,特异地释放于肠道粘膜,发挥其强大的抗炎作用.就新型糖皮质激素在炎症性肠病治疗中的有效性和安全性做简要评估和总结.     

Classical Chinese Herbal Formulas in the Treatment of Coronary Heart Disease: A Narrative Review

Objective:To summarize the current evidence for 8 frequently prescribed Chinese herbal formulas(CHF)as treatments for angina pectoris in patients with coronary heart disease(CHD)and the associated adverse reactions.Methods:Seven electronic databases were screened from their inception through July 2018 for all evidence related to classical CHF for the treatment of patients with CHD.Results:CHF improves CHD outcomes in terms of angina pectoris,electrocardiogram results,Chinese medicine syndromes and biomarkers iomarkers.The combination of CHF and Western medicine(WM)is more effective on CHD than WM alone.The use of CHF to treat CHD shows the same or better clinical effects as the use of WM alone.The 8 investigated CHF do not induce hepatic and renal toxicity or other serious adverse effects.Conclusions:The safety and efficacy of 8 frequently prescribed herbal formulas for treating CHD have been confirmed in many studies.The findings of these studies are positive but should be interpreted cautiously due to the poor methodological quality of the randomized controlled trials(RCTs)and meta-analyses.Additional high-quality,multi-center,large-sample RCTs should be performed to confirm these results.     

Effect of Chinese herbal medicine combined with acitretin capsule in treating psoriasis of blood-heat syndrome type

Objective:To observe the clinical curative effect of Chinese herbal medicine combined with acitretin capsule in treating psoriasis of blood-heat syndrome(P-BH).Methods:Eighty patients of P-BH were randomly assigned to two groups,39 in Group A and 41 in Group B.Both was treated with Chinese herbal medicines for clearing heat,cooling blood and removing toxic substance,and acitretin capsule was given to Group A additionally,with 8 weeks as one therapeutic course.The clinical curative effect was compared bet...     

Systematic Review on Randomized Controlled Trials of Coronary Heart Disease Complicated with Depression Treated with Chinese Herbal Medicines

Objectives: This systemic review evaluated the efficacy and safety of Chinese herbal medicines (CHMs) in patients with coronary heart disease (CHD) complicated with depression. Methods: All databases were retrieved till September 30, 2014. Randomized controlled trials (RCTs) comparing CHMs with placebo or conventional Western medicine were retrieved. Data extraction, analyses and quality assessment were performed according to the Cochrane standards. RevMan 5.3 was used to synthesize the results. Results: Thirteen RCTs enrolling 1,095 patients were included. Subgroup analysis was used to assess data. In reducing the degree of depression, CHMs showed no statistic difference in the 4th week [mean difference (MD)=–1.06; 95% confidence interval (CI) –2.38 to 0.26; n=501; I2=73%], but it was associated with a statistically significant difference in the 8th week (MD=–1.00; 95% CI –1.64 to –0.36; n=436; I2=48%). Meanwhile, the combination therapy (CHMs together with antidepressants) showed significant statistic differences both in the 4th week (MD=–1.99; 95% CI –3.80 to –0.18; n=90) and in the 8th week (MD=–5.61; 95% CI –6.26 to –4.97; n=242; I2=87%). In CHD-related clinical evaluation, 3 trials reported the intervention group was superior to the control group. Four trials showed adverse events in the intervention group was less than that in the control group. Conclusions: CHMs showed potentially benefits on patients with CHD complicated with depression. Moreover, the effect of CHMs may be similar to or better than antidepressant in certain fields but with less side effects. However, because of small sample size and potential bias of most trials, this result should be interpreted with caution. More rigorous trials with larger sample size and higher quality are warranted to give high quality of evidence to support the use of CHMs for CHD complicated with depression.     

A Summary and Evaluation of Current Evidence for Myocardial Infarction with Chinese Medicine

Objective: To provide evidence-based recommendations for clinical application and provoke thoughts for future researchers by conducting a comprehensive summary and evaluation of the current evidence profile for the role of Chinese medicine(CM) in treating myocardial infarction(MI). Methods: Online databases including Pub Med, EMBase, Cochrane Library, Chinese National Knowledge Infrastructure(CNKI), Chinese Biomedical Medicine(CBM), VIP Journal Integration Platform, and Wanfang database were systematically searched for literatures on CM in treating MI. After screening, studies were categorized into 5 types, i.e. systematic review(SR), randomized controlled trial(RCT), observational study, case report and basic research. General information was abstracted, and the quality levels of these studies and their conclusions were summarized and assessed. Results: A total of 452 studies including 10 SRs, 123 RCTs, 47 observational studies, 28 case reports, and 244 basic researches were selected. Clinical studies centered primarily on herbal decoction and mostly were not rigorously performed. High-quality studies were predominantly on Chinese patent medicines(CPMs) such as Danshen Injection(丹参注射液), Shenmai Injection(参麦注射液), Shengmai Injection(生脉注射液) and Qishen Yiqi Dripping Pills(芪参益气滴丸). The most frequently observed pattern of drug combination was decoction plus injection. Results of SRs and clinical studies showed that CM may reduce mortality, decrease risk of complication, reduce myocardial injury, improve cardiac function and inhibit ventricular remodeling. Findings from basic researches also supported the positive role of CM in reducing infarct size and myocardial injury, promoting angiogenesis, preventing ventricular remodeling and improving cardiac function. According to the current evidence body, CM has proven effects in the prevention and treatment of MI. It is also found that the effects of CPMs vary with indications. For instance, Shenmai Injection has been found to be especially effective for reducing the incidence of acute clinical events, while CPMs with qi-nourishing and bloodcirculating properties have been proven to be effective in inhibiting ventricular remodeling. High quality evidence supports the use of CM injection for acute MI and CPM for secondary prevention. Reports on adverse events and other safety outcomes associated with CM for MI are scarce. Conclusions: Sufficient evidence supported the use of CM as an adjuvant to Western medicine for preventing and treating MI. The choice of drug use varies with disease stage and treatment objective. However, the quality of the evidence body remains to be enhanced.     

下肢慢性溃疡中医外治进展

文章主要对中医外治下肢慢性溃疡的临床治疗进展进行综述,从病因病机、中药单方、中药鲜品、中药复方、中药熏洗、针灸疗法及刺血疗法等7个方面进行分析归纳总结,虽然中医药治疗本病疗效显著,但目前尚没有统一的治疗思路及方法,其治疗仍停留在临床经验治疗上,该病的诊治规范化、系统化和个体化研究还有待于进一步探讨。     

Non-scientific Classification of Chinese Herbal Medicine as Dietary Supplement

This article focuses the category status of Chinese herbal medicine in the United States where it has been mistakenly classifified as a dietary supplement. According to Yellow Emperor Canon of Internal Medicine (Huang Di Nei Jing), clinical treatment in broad sense is to apply certain poisonous medicines to fight against pathogeneses, by which all medicines have certain toxicity and side effect. From ancient times to modern society, all, or at least most, practitioners have used herbal medicine to treat patients’ medical conditions. The educational curriculums in Chinese medicine (CM) comprise the courses of herbal medicine (herbology) and herbal formulae. The objective of these courses is to teach students to use herbal medicine or formulae to treat disease as materia medica. In contrast, dietary supplements are preparations intended to provide nutrients that are missing or are not consumed in suffificient quantity in a person’s diet. In contrast, Chinese herbs can be toxic, which have been proven through laboratory research. Both clinical practice and research have demonstrated that Chinese herbal medicine is a special type of natural materia medica, not a dietary supplement.     

四种中草药抗柯萨奇及埃柯病毒的实验研究

在培养的细胞上研究探讨了四种中草药(贯众、虎杖、金银花、连翘)对病毒性心肌炎及其抗病毒作用的机制。实验结果证明:四种中草药细胞外抑制 COX β_3V 及 ECHO19V 的作用很明显(P<0.05)。为治疗病毒性心肌病及其它病毒性疾病提供了用药依据。