Application Research of Earned Value Management in New Drug Research and Development Projects

Objective To help investors assess and control the costs of new drug development and reduce the risks of new drug development projects.Methods Cost analysis and financial forecasting were carried out with the integrated approach of earned value management.According to the principle of earned value management deviation analysis,the basic process of the new drug research and development project was combined with the hypothesis method from the research of Tufts Drug Development Research Center.Results and Conclusion If the project progress check was carried out in the clinical trial,the project costs were found overspent,the efficiency was low,the project progress was faster,and the resource investment was ahead.It is recommended that the adjustment should be made to reduce the input of resources,and increase the efficient key personnel to take the place of some less efficient staff.

Intellectual Property Protection and High Quality Development of Radix Glycyrrhizae for Treatment of COVID-19

Radix Glycyrrhizae is the dominant native medicinal material variety in the north and northwestern medicinal materials producing areas.It is a main Chinese medicine of effective TCM drugs and formulas for the treatment of new coronavirus disease(COVID-19).This paper introduces the medicinal value of Radix Glycyrrhizae,involving the labeling,cultural heritage,and creative intellectual property rights of the Chinese medicinal materials,analyzes the poverty-stricken areas that are ecologically suitable for Radix Glycyrrhizae cultivation,and the superior counties and production bases of the Chinese medicinal materials.Besides,mainly from the aspects of perfect intellectual property rights,the establishment of authentic medicinal material production bases,and the construction of quality control systems,etc.,it discusses the rural revitalization strategy and the development strategy of traditional Chinese medicine(TCM),agricultural intellectual property protection and high-quality development strategy of Radix Glycyrrhizae.

Opinion on pharmacology research and new drug development from precision medicine

Since President Obama announced the Precision Medicine Initiative from a national strategy perspective in his State of the Union address,precision medicine has rapidly become a world-wide hotspot and drawn global attention in the medical field.Precision medicine aims at applying genetic information of individual diseases to guide his or her diagnosis and treatment.

A Review on the Research of Precision Medicine for Cancer Based on the Integration of Traditional Chinese and Western Medicine

Objective:To summarize and expound the general situation of precision medicine for cancer according to the current international research hot spots and treatment frontiers of cancer.Methods:This article makes an inventory from five aspects of treatment methods,detection technology,new drug research and development,information data and traditional Chinese medicine,"from point to surface","from outside to inside"and"integration of Chinese and Western medicine",to explore the whole picture of tumor treatment and research.Results:With the rapid development of tumor precision medicine in recent years,the tumor treatment methods have been developed from single to multiple.The research technology has been changed from macro to micro.The therapeutic drugs have been changed from systemic chemotherapy to targeted therapy,immunotherapy and other technologies.The treatment concept has been changed from local to overall.And the integrated treatment methods of traditional Chinese and Western medicine have brought a new chapter to tumor treatment.Conclusion:Through a series of new technologies,new methods and new concepts,tumor precision medicine promotes the treatment of tumors with integrated Chinese and Western medicine into a new chapter.

Analysis of Strategy for Extending Patent Protection of Rucaparib

As a knowledge-intensive and promising strategic emerging industry, the biomedical industry has high entry thresholds, large R&D investment, long cycle, high risk and high return. In all technical fields, the biomedical industry has the highest dependence on intellectual property rights, and the protection of pharmaceutical intellectual property rights by domestic and foreign biomedical enterprises also runs through the whole process of drug research and development. Extending the patent protection period of drugs as well as forming and strengthening patent fortresses requires a patent network that surrounds drugs to maximize the value of intellectual property protection, which is also the focus of every pharmaceutical company with patent rights. By analyzing the patent portfolio of Clovis Oncology Company in the United States on Rucaparib and the patent portfolio of other companies or applicants on Rucaparib, we can have a clearer understanding of the strategy of extending the patent protection period of a new drug product.

Network pharmacology-based elucidation of molecular biological mechanisms of Qizhu Yuling Decoction for treatment of esophagus cancer

Objective:To investigate the active compounds,key targets and molecular mechanism of Qizhu Yuling Decoction in the treatment of esophageal carcinoma based on network pharmacology.Methods:The active compounds of Qizhu Yuling Decoction with anti-esophageal cancer activity were screened by TCMSP and literature search,and the drug targets were searched by DrugBank and predicted by SwissTargetPrediction.The esophageal cancer-related genes were obtained from GeneCards,OMIM,DrugBank,TTD,DisGeNET,and the intersection network was selected to obtain candidate genes.The"herb-compound-target-disease"network was constructed with Cytoscape,the PPI network was constructed in STRING and core network modules were screened.Gene ontology and KEGG enrichment analysis was performed by using Metascape,and the"pathway-gene"network was constructed to further screen key targets.Results:A total of 47 active compounds(19 Astragalus,4 Zedoary turmeric,11 Atractylodes macrocephala,9 Curcuma longa,5 Clematis root,and 5 Salvia chinensis),297 candidate genes,2413 GO and 119 KEGG pathways were obtained.Conclusion:The active compounds of Qizhu Yuling Decoction in the treatment of esophageal cancer are quercetin,kaempferol,glycine and ursolic acid.The potential targets are AKT1,MAPK1,MAPK3,PIK3R1 and RELA.GO involves oxidative stress,cell cycle,apoptosis and cell death,and KEGG involves typical cancer pathways,MAPK,NF-κB and PI3K-Akt signaling pathways.This study reveals the molecular biological mechanism of Qizhu Yuling Decoction in the treatment of esophageal cancer,and speculates that the function of potential targets focuses on the interaction of multiple signaling pathways,which can antagonize the proliferation,invasion,metastasis and recurrence of esophageal cancer and improve the prognosis of patients.This study provides new evidence for subsequent new drug development,clinical application and experimental study.

医疗机构基于“三结合”中药新药研发及管理体系的构建

目的:在中药审评审批制度改革的政策背景下,围绕医疗机构,探索中医药理论、人用经验和临床试验相结合(简称“三结合”)的审评证据体系落地举措,为医疗机构中药制剂及中药新药研发提供参考。方法:根据“三结合”审评证据体系下中药新药研发的相关要求,从机构层面加强人用经验研究相关配套建设,从管理层面搭建中药研发、成果转化服务平台,从临床层面规范开展人用经验研究,构建医疗机构中药新药研发及管理体系。结果:医疗机构中药新药研发及管理体系的构建,有助于将临床诊疗数据转变为支持中药新药注册的人用经验证据,通过提高中药研发水平促进中药新药转化。结论:在医疗机构构建基于“三结合”的中药新药研发及管理体系,是“三结合”审评证据体系落地、政策引导研发实践的路径之一。

新药研究与开发课程思政教学探索

在新药研究与开发课程教学中融入课程思政理念,将其与学科教学内容融合,发挥思政课程与课程思政的协同效应,是以专业技能知识为载体开展育人工作的必由之路。这一教学改革可有效推进以创新为核心的学生综合能力培养,是成功实现“健康中国”战略下复合型药学人才培养的有效途径。

同质化教学条件下参与科研创新实践对临床药学专业本科生新药研究与开发课程成绩的影响

大学生参与科研创新实践是高校人才培养的重要环节。本文收集某高校临床药学专业本科生参与科研创新实践的信息,分析同质化教学条件下参加科研创新实践对其在新药研究与开发课程中成绩的影响。结果表明,参加科研创新实践可以有效提升临床药学专业本科生新药研究与开发课程成绩,提高其对基本概念的理解能力和科研实验设计能力。

正电子发射计算机断层显像在中枢神经系统药物研发中的应用

正电子发射型计算机断层显像技术(positron emission tomography,PET)在中枢神经系统(CNS)药物研发中发挥重要作用。PET可以定量研究CNS药物在脑组织体液中的生物分布,药代动力学,与靶点相互作用,提供药物浓度与受体占有率的定量关系。本综述总结了PET在CNS药物研发中的定量分析手段,包括药代动力学分析以及受体占有率分析中常用的方法与数学公式。同时,本综述也总结了PET在CNS新药研发中的应用,为后续CNS的新药研发提供新的思路与方向。

代谢仿生导向的中西医融升路径

中医和西医各有优缺点,且具有互补性。中西医结合已成为我国医学体系的重要特色,但中西医理论与实践的深度融合与发展仍有待突破。本文针对复杂慢病的临床诊疗需求,梳理了推动中西医融升、构建新医学理论体系亟需解决的关键科学技术难题,阐释了代谢调控在促进中西医理论融合、满足临床治疗需求中的潜在作用,进而从“代谢仿生”角度提出了中西医融合促进慢病治疗策略创新与组合新药研发的可能路径,以期为全人类健康贡献中国医学智慧。

我国抗肿瘤药物临床试验研究热点

目的 总述我国抗肿瘤药物临床试验研究热点。方法 提取药物临床试验登记与信息公示平台2013年至2020年登记的我国(该平台未收录香港地区、澳门地区、台湾地区相关信息)除生物等效性试验外的抗肿瘤药物临床试验信息,包括药物类型、临床试验分期、药物靶点、申办者、机构等。采用Gephi 0.9. 2软件生成社会网络合作图。结果 共纳入2 143项抗肿瘤药物临床试验,其中2014年和2015年的数量较少(97项、104项),从2016年起逐年增加(从211项增至477项);其中,药物类型以化学药物的临床试验最多(1 238项),以试验分期Ⅰ期药物临床试验数量最多(951项)。共涉及药物靶点99种(除未披露的外),药物临床试验数量排前3的药物靶点为程序性死亡受体-1/程序性死亡配体-1(PD-1/PD-L1,281项,13.11%),表皮生长因子受体(128项,5.97%),人表皮生长因子受体2(79项,3.69%);临床试验适应证主要集中于实体瘤(389项)、肺癌(382项)、乳腺癌(239项)、淋巴瘤(229项)、肝癌(148项)。共722个申办者与617个药物临床试验机构建立合作关系;开展抗肿瘤药物临床试验较多的申办者分别为江苏恒瑞医药股份有限公司、上海恒瑞医药有限公司、正大天晴药业集团股份有限公司,机构分别为北京大学肿瘤医院、河南省肿瘤医院、哈尔滨医科大学附属肿瘤医院。结论 PD-1/PD-L1是肿瘤靶向治疗领域最热门的药物靶点。开展抗肿瘤药物临床试验应密切关注我国有关新药研发和注册的政策法规和指导原则,并关注具有临床价值的肿瘤创新药或改良型新药的研发。

甘肃祁连山冬虫夏草内生真菌的分离及其代谢产物活性评价

目的分离甘肃祁连山冬虫夏草内生真菌,并探讨其代谢产物的生物活性。方法采用3种不同培养基,用组织匀浆法和组织切块法对冬虫夏草不同部位内生真菌进行分离纯化。分别对其代谢产物的酶抑制活性、抗菌和抗氧化活性进行评价。利用形态学和分子生物学方法进行高活性菌株分类鉴定,利用现代色谱分离技术对高活性化学成分进行跟踪分离。结果分离得到42株内生真菌,发酵得到84个待测样品,对腺苷脱氨酶(ADA)抑制活性>40%者占比52%。其中高活性菌株Aspergillus sp.C-1乙酸乙酯相样品ADA抑制活性>90%,对5种供试菌均有抑菌活性,二苯基苦基苯肼(DPPH)和羟自由基清除率均>85%,总还原力为(0.039±0.002)mg的L-抗坏血酸(VC)当量,分子鉴定与Aspergillus fumigatus有99%同源性。追踪分离出2个具有ADA抑制活性的化合物,其中C1被鉴定为大黄素甲醚(physcion),IC_(50)为3.58 mmol/L。结论甘肃祁连山冬虫夏草内生真菌资源丰富且次级代谢产物具有良好的生物活性,是活性物质发现的良好来源。

新药研发技术服务型人才培养中的PTP大思政教育模式探讨

杭州医学院药学专业为满足国家对新药研发技术服务型人才的迫切需求,实施了基于实践-理论-实践(practice-theory-practice,PTP)的大思政教育模式,通过整合假日课堂、学校小课堂和社会大课堂的资源,构建了一个以职业需求为导向、实践能力培养为核心的综合教育体系。在假日课堂中,学生参与社会实践活动,增强职业素养;在学校小课堂中,专业理论与思政教育相结合,提升学生的专业知识和政治素养;在社会大课堂中,安排学生在实际工作环境中进行实习和开展科研项目,提高解决复杂问题的能力。PTP大思政教育模式的实施,有效提升了学生的知识水平、实践技能和思政素养,培养了具有良好职业道德和社会责任感的药学人才。未来,将继续优化PTP大思政教育模式,通过深化产教融合、创新教育方法、完善评价机制等措施,进一步提高教学质量,为新药研发领域输送更多高素质的技术服务型专业人才。

猫传染性腹膜炎的研究进展及新药开发的可行性分析

猫传染性腹膜炎(FIP)是由猫冠状病毒(FCoV)突变引起的一种猫科动物高致命性疾病,曾因缺乏有效的治疗药物而被视为不治之症。新型冠状病毒感染(COVID-19)疫情加速了抗冠状病毒药物的研究进程,近年来多款药物通过添加新适应证已获批准用于治疗COVID-19,并在一定程度上取得了显著疗效,医学研究的进步也为兽医领域中FIP的治疗带来了新方向。文章总结了FIP的流行病学以及目前主要的治疗方案,之后从抗病毒机制入手探讨了几种抗COVID-19药物与猫传染性腹膜炎病毒(FIPV)的内在联系,以期为临床治疗FIP的新药开发提供参考。

基于案例引导和研讨教学融合的多模态教学在新药研究与开发课程中的应用

目的:分析多模态教学在新药研究与开发课程教学中的应用效果。方法:选取皖南医学院2018、2019级临床药学的学生作为研究对象,比较传统教学和多模态教学模式在新药研究与开发课程中的教学效果。2018级学生(n=61)采用传统教学模式教学,2019级学生(n=57)采用多模态教学。从平时成绩、期末考试成绩和问卷调查3个方面对教学效果进行评价。结果:研究组学生的平时成绩、期末考试成绩和成绩优良率[(84.00±8.27)分、(82.74±5.32)分、82.45%]均高于对照组[(74.90±2.31)分、(72.72±11.68)分、24.59%](P<0.05),且问卷调查结果显示研究组学生对教学方式的满意度及教学效果认可度也高于对照组(P<0.05)。结论:多模态教学模式可以有效激发学生的学习兴趣,提高学生成绩,总体教学效果优于传统教学模式。

新质生产力赋能中药新药临床研究:现状、问题与展望

在新质生产力的发展浪潮中,医疗大数据、人工智能等先进技术在中药新药研发领域发挥着重要的作用。对新质生产力及其创新技术在中药新药临床试验各个关键环节的应用现状进行系统综述,包括处方组成及优化、临床试验的精准定位、试验方案的科学设计、数据的收集与管理、试验过程的质量控制及对有效性和安全性的评价等。此外,还深入分析了科技创新成果在实际应用过程中遇到的具体挑战,如数据安全性及受试者隐私保护、结果的可靠性和可解释性、算法模型的精确性和普适性、跨学科合作的复杂性等;并在此基础上展望了未来的发展方向,即继续深化新质生产力及其创新技术在中药新药研发中的应用,特别是融合人工智能、医疗大数据等技术以进一步释放中药研发的新潜能。

中药源手性药物研究进展与述评

手性化合物在自然界中广泛存在。许多天然药物分子均含有手性中心,且药物的药理活性与分子的手性结构密切相关。在已知的传统中药体系中,存在着大量的手性药物分子,这些药物分子被广泛应用于各类临床治疗诊断中。因此,研究手性分子在中药中的存在形式和作用机制,对于深入探索中药的药理、药效至关重要。以中药中的手性天然药物分子为研究对象,旨在阐述其手性结构、化学与生物合成方法、药理活性与手性的相关性,以及手性药物在临床应用中的重要进展,探讨中药源手性药物研发的前景。

浅谈独立评审委员会(IRC)在创新药研发中的重要价值

在药物/医疗器械研发临床试验中,尤其是抗肿瘤药物临床试验中,主要终点有时需要由影像来进行评估。当临床试验采用影像相关终点作为主要研究终点时,为保障评估的客观性和稳定性,通常会在临床研究中设置独立评审委员会(Independent Review Committee,IRC),即“独立影像评估”。IRC采用标准化影像评价程序,提供影像方案标准化、改善数据质量、减少偏倚和差异性以及为监管机构审批提供依据,在影像学临床试验中发挥重要作用。IRC适用范围主要包括安全性的评估、疗效/有效性的评估、影像学数据、病理学数据和照片数据。IRC可提高影像评估的客观性、可靠性,助力新药研发,为制药行业带来更多获益。本研究在梳理IRC发展历史的基础上,简述了国内外监管机构对IRC设置和运行的相关指导要求,分析了IRC对于药物/医疗器械研发的价值,总结了IRC的工作内容、适用场景和常用的评估标准,并对IRC未来的发展方向进行了展望,旨在为更多的新药研发提供经验和参考。