Simultaneous and interference-free determination of eleven nonsteroidal anti-inflammatory drugs illegally added into Chinese patent drugs using chemometrics-assisted HPLC-DAD strategy

In this work, a smart strategy that combines three-way high performance liquid chromatography-diode array detection(HPLCDAD) data with second-order calibration method based on alternating trilinear decomposition(ATLD) algorithm was proposed for simultaneous determination of eleven non-steroidal anti-inflammatory drugs(NSAIDs) illegally added into Chinese patent drugs and health products. All target analytes were rapidly eluted out within 14.5 min under a simple gradient elution. With the aid of the prominent "second-order advantage" of the ATLD algorithm, three HPLC problems, i.e. peak overlaps, unknown interferences and baseline drift, could be mathematically calibrated, and pure signals of target analytes could be extracted out from heavy-interference but information-rich HPLC-DAD data. The average spiked recoveries for all target analytes were in the range of 95.9%–106.4% with standard deviations lower than 7.5%. Validation parameters including sensitivity(SEN), selectivity(SEL), limit of detection(LOD), limit of quantitation(LOQ) and precisions of intra-day and inter-day were calculated to validate the accuracy of the proposed method, quantitative results were further confirmed by the classic HPLC method, which proved that chemometrics-assisted HPLC-DAD analytical strategy was highly efficient, accurate and green for drug-abuse monitoring of NSAIDs in Chinese patent drugs and health products.

Analysis on Composition Rules of Chinese Patent Drugs Treating Pain-Related Diseases Based on Data Mining Method

Objective: To analyze the composition rules of oral prescriptions in the treatment of headache, stomachache and dysmenorrhea recorded in National Standard for Chinese Patent Drugs(NSCPD) enacted by Ministry of Public Health of China and then make comparison between them to better understand pain treatment in different regions of human body. Methods: Constructed NSCPD database had been constructed in 2014. Prescriptions treating the three pain-related diseases were searched and screened from the database. Then data mining method such as association rules analysis and complex system entropy method integrated in the data mining software Traditional Chinese Medicine Inheritance Support System(TCMISS) were applied to process the data. Results: Top 25 drugs with high frequency in the treatment of each disease were selected, and 51, 33 and 22 core combinations treating headache, stomachache and dysmenorrhea respectively were mined out as well. Conclusions: The composition rules of the oral prescriptions for treating headache, stomachache and dysmenorrhea recorded in NSCPD has been summarized. Although there were similarities between them, formula varied according to different locations of pain. It can serve as an evidence and reference for clinical treatment and new drug development.

Research on the World’s Most Valuable Antihypertensive Drugs Based on Patent Analysis

Objective To find out several patented technologies of antihypertensive drugs with the most market value through analysis,and provide a reference for the research and development of enterprises.Methods The most valuable patented technologies of antihypertensive drugs from 2009 to 2019 were analyzed to explore the patent layout and technical characteristics of the main patent applicants,and then the key directions of their research and development were gotten.Results and Conclusion Based on the method of patent analysis,five patents with the most market value are extracted to provide important technical support and market value reference for the research and development of generic drugs or new drugs.

药品集采政策与药企研发行为

药品集采政策会加剧医药行业竞争,从而影响医药企业的研发投入。基于药品集采前后三年医药企业的研发专利样本,针对药品集采政策对药企研发行为影响的回归结果表明,集采政策的实施会增加医药企业的研发专利数量,但医药企业所面临的转换成本和集采的预期市场收益,会影响医药企业的研发行为,并进一步影响医药企业的创新效率。因此,要降低医药行业的制度成本,加强医药企业之间的分工合作和并购重组,提升医药企业的创新效率,从而加快完善药品集中采购制度和推动健康中国的政策落实。

Current State of Nanoemulsions in Drug Delivery

Nanoemulsions have attracted great attention in research, dosage form design and pharmacotherapy. This is as a result of a number of attributes peculiar to nanoemulsions such as optical clarity, ease of preparation, thermodynamic stability and increased surface area. Nanoemulsions also known as submicron emulsions serve as vehicles for the delivery of active pharmaceutical ingredients as well as other bioactives. They are designed to address some of the problems associated with conventional drug delivery systems such as low bioavailability and noncompliance. The importance of design and development of emulsion nanocarrier systems aimed at controlling and/or improving required bioavailability levels of therapeutic agents cannot be overemphasized. Reducing droplet sizes to the nanoscale leads to some very interesting physical properties, such as optical transparency and unusual elastic behaviour. This review sheds light on the current state of nanoemulsions in the delivery of drugs and other bioactives. The morphology, formulation, characteristics and characterization of nanoemulsions were also addressed.

Analysis of Technological Developments in the Treatment of Alzheimer’s Disease through Patent Documents

Population aging and the consequent change in the profile of the age pyramid are already a reality the world over. One undeniable effect of this aging process is the significant increase in the number of people with Alzheimer’s disease (AD), which is the most common form of dementia, accounting for around 50% - 60% of all cases. AD tends to affect people in their 60 s, becoming progressively more commonplace in older age groups. It is an incurable disease, and patients can live for many years taking medication on a daily basis. This study shows that research into AD is on the rise around the world because the pharmaceutical industry and research institutions are seeking new types of drugs to treat and even cure Alzheimer’s patients. By analyzing patent documents, we map out the potential future treatments for this disease, indicating the leading countries and drugs companies that have invested most in a bid to accelerate progress towards new discoveries about the disease and the development of new drugs.

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.

仿制与原研利伐沙班预防髋膝关节置换术后深静脉血栓有效性与安全性比较

目的 评估仿制与原研利伐沙班预防人工髋关节置换术(THA)或人工膝关节置换术(TKA)后深静脉血栓(DVT)的有效性与安全性。方法 收集医院关节外科2016年7月至2022年12月收治拟行THA(96例)或TKA(63例)的患者,按所用利伐沙班来源的不同分为原研组(91例)和仿制组(68例),并随访术后3个月内DVT与药品不良反应发生率。结果 原研组及仿制组术后DVT发生率分别为4.40%和5.88%,出血事件发生率分别为1.10%和0,其他不良反应(便秘、疼痛、下肢肿胀)发生率分别为3.30%和7.35%,组间比较均无统计学差异(P> 0.05)。结论 THA或TKA术后使用仿制与原研利伐沙班的有效性与安全性相当。

中成药治疗肾性贫血及其临床研究现状

目的分析并梳理中成药治疗肾性贫血的临床研究,以期为临床实践和未来研究方向提供参考。方法系统检索8个中英文数据库,收集中成药治疗肾性贫血的临床研究。采用描述性总结与图表结合的形式对结果进行展示。结果共纳入60篇研究,其中首篇关于中成药治疗肾性贫血的临床研究发表于2000年,绝大部分研究发表于近5年。研究类型最多的是随机对照试验,占比90%。关于透析依赖性肾性贫血的研究40篇,研究对象2916例;非透析依赖性肾性贫血研究2篇,研究对象174例;未提及透析或者非透析依赖的肾性贫血研究有18篇,研究对象1279例。临床研究中干预措施的对比形式主要是中成药联合西药与单用西药的对比。纳入的研究中有40篇将“血红蛋白的变化”设定为一项结局指标,其次是“总有效率”(35篇)。结论现阶段治疗肾性贫血的中成药种类繁多,其有效性和安全性尚待进一步研究。此外,临床研究的结局指标不一致,无法保证研究的科学性和严谨性。

药品数据专有权国际立法溯源与中国制度安排

药品上市审批对于药品安全有效性数据的专门审查要求,造就了涉及药品数据的独特知识产权保护机制。基于药品数据获取的高昂投入及其对于药品仿制与后续创新的重要价值,美欧发达国家在世界范围内率先建立了药品数据保护机制,其逐渐成为一项国际性的法律规则。无论是美欧发达国家的立法,还是相关国际法律规则,对于药品数据的知识产权保护都呈现从商业秘密模式向专有权机制转变的立法格局。产业利益驱动无疑是其中的一个重要诱因,但归根结底是源自药品数据专有权有效兼顾原研发药企经济利益与社会公众健康权益的制度优势。鉴于此,在药品数据专有权保护的国际趋势下,我国应从本土药品产业激励创新与规范仿制的基本诉求出发,以必要的内部限制与外部监管明确药品数据专有权的法律边界,并通过药品数据动态化公示平台的设置与药品数据付费使用模式的创设,建构起与药品专利制度有机衔接的数据专有权保护机制。

药品专利信息登记反垄断问题研究

在药品专利纠纷早期解决机制中,药品上市许可持有人有义务保证所登记药品专利信息的完整性和准确性。药品上市许可持有人在具有市场优势地位情况下实施滥用药品专利信息登记权利的行为,有可能构成反垄断违法行为,需要进行反垄断规制。反垄断执法专门机构可以规范药品专利信息登记行为,仿制药企业可以提起反垄断民事诉讼,由此排除或者修正错误登记的药品专利信息。药品专利权人主观故意可以作为滥用垄断地位行为的构成要件,应当防止不适当地扩大药品专利信息登记的专利权范围。药品上市许可持有人应当在修改或者删除错误登记的药品专利信息以及对仿制药企业进行损害赔偿等方面承担法律责任。

基于2020年版《中国药典》一部含毒性动物饮片中成药梳理分析与药学监护要点建立

目的分析含毒性动物饮片中成药,并建立其临床使用监护要点。方法根据2020年版《中国药典》收载的8味含毒性动物饮片,筛选药典中收载的含毒性动物饮片的中成药目录,梳理其药品说明书各项内容并整理其用药监护等内容。结果共纳入94种含毒性动物饮片中成药,按功能分类多集中于理血剂、开窍剂、补益剂等方面,其中含1种毒性动物饮片的有65种,含2种毒性动物饮片的有19种,含3种毒性动物饮片的有7种,含4种毒性动物饮片的有3种。多数含毒性动物饮片的中成药说明书标注了妊娠、哺乳、经期、儿童、肝肾功能异常等用药禁忌,且部分说明书标注了用药疗程等信息,需加强用药监护。结论含毒性动物饮片中成药是需加强用药监护的一类药品,需关注药品说明书标注的特殊人群、患者基础疾病、用药疗程、药物相互作用等方面,同时,还应注意长期使用此类药品可能导致毒性动物饮片的毒性成分蓄积和不良反应等情况,从而保证临床用药安全。

美国药品专利“常青”行为的规制经验及其借鉴

药品专利“常青”是专利药企业通过延长核心专利药的产品生命周期来获取高额利润的行为。目前,我国对药品专利“常青”行为的规制经验不足。为有效预防和规制该行为,有必要以首例反向支付协议案为线索,洞察药品专利“常青”行为在实务中存在的问题,探究其目的及表现形式并考察美国的规制经验。最终提出我国规制药品专利“常青”行为应秉持利益平衡原则、提高创造性授权标准、要求“反向支付协议”事先报备和事后审查以及明确并细化“专利药跳转”行为规则的应对策略。

我院2018—2022年补益类中成药的应用分析

目的 分析2018年1月—2022年12月我院补益类中成药的应用现状及趋势,为此类药的合理使用提供参考。方法 统计2018年1月—2022年12月药品数据库中补益类中成药年销售金额和用量进行统计,分析补益类中成药的销售金额、用药频度(DDDs)、日用药金额(DDC)、总金额排序号/DDDs排序号(DUI)值。结果 补益类中药口服剂型用药金额呈逐年上升趋势,注射剂构成比呈逐年下降趋势。口服剂型得到越来越广泛的应用,但是价格偏高。结论 我院补益药中成药品种结构基本合理,常用的补益药DDC值偏高,患者经济负担过重。补益药的不良反应发生率逐年增加,应注重合理用药。

从国家药品抽检角度分析已上市中成药需要关注的相关问题

药品抽检是药品监督和执法的重要技术支撑手段,通过分析抽检结果可有效发现上市后药品的质量风险,同时也可评价某类或一定区域内药品的质量。立足于历年国家药品抽检中发现的中成药品种质量问题和潜在安全风险,以与中成药质量相关的原料、生产工艺、辅料及包装材料等环节为切入点,分析已上市中成药需要关注的问题,以期为中成药质量的提升和监管工作的开展提供参考。

论药品专利补充实验数据的接受标准

药品专利由于研发时间长,在申请日后会产生大量的补充实验数据。我国的立法及实践已明确,应当对补充实验数据进行审查。但审查不等于被接受,典型案例反映出,对补充实验数据的接受标准依然存在较大争议。域外美国、欧洲、日本的立法模式和司法实践也各不相同。解决当前药品专利补充实验数据接收标准所存在的问题,应当从以下几个方面进行着手:分别规定“技术方案”和“预测效果”不同的接受标准;厘清补充实验数据与证明目的之间的关系;放宽对预测效果的严格标准;广泛理解本领域公知常识及现有技术。

原研与仿制苯磺酸氨氯地平治疗高血压的有效性和安全性比较

目的比较原研与仿制苯磺酸氨氯地平治疗高血压的有效性和安全性。方法选取2021年1月1日至6月30日在西安交通大学第一附属医院分别接受苯磺酸氨氯地平原研药和仿制药进行高血压治疗的患者243例和272例,采用倾向性匹配分析法匹配(1∶1)为原研组和仿制组,各155例。两组患者均持续治疗3个月。结果治疗后,两组患者的收缩压、舒张压和脉压差均显著降低(P<0.05),但差异无统计学意义(P>0.05)。两组患者的临床疗效、用药依从性优良率、不良反应发生率比较,差异均无统计学意义(P>0.05)。结论原研与仿制苯磺酸氨氯地平治疗高血压的有效性、用药依从性和安全性均相当。

分析标准化药物治疗症状性动脉导管未闭对早产儿预后的影响

目的 分析标准化药物治疗症状性动脉导管未闭(symptomatic patent ductus arteriosus,s PDA)的效果。方法 非随机选取2017年1月—2021年12月甘肃省兰州市妇幼保健院新生儿科收治的86例s PDA早产患儿,按治疗方式分为两组,各43例。两组均采取标准化药物治疗,对照组实施布洛芬治疗,观察组实施对乙酰氨基酚治疗,对比两组的治疗效果。结果 两组动脉导管关闭率及重新开放率比较,差异无统计学意义(P均>0.05)。两组经鼻持续气道正压通气时间、住院时间比较,差异无统计学意义(P均>0.05)。观察组消化道出血发生率为2.3%(1/43),低于对照组的16.3%(7/43),差异有统计学意义(χ^(2)=4.962,P<0.05)。两组并发症发生率比较,差异无统计学意义(P均>0.05)。结论 在s PDA标准化药物治疗过程中,布洛芬及对乙酰氨基酚都能够发挥良好的治疗效果。相较而言,对乙酰氨基酚引发的消化道出血不良反应更少,应用安全性更高。

某三甲医院2022年产科中成药不合理使用情况分析

目的:促进医院产科中成药的合理应用,保障孕产妇及婴儿用药安全。方法:利用临床用药决策支持软件对某三甲医院产科2022年度开具的中成药处方进行系统自动点评筛选,对筛选出的问题处方再次进行人工点评,对处方存在的问题类型进行归纳汇总,分析原因。结果:该院产科2022年开具中成药处方(含住院医嘱)共计14886张,系统智能筛选出问题处方3987张(26.78%),人工点评后确认存在用药不合理情况的处方199张(1.34%),其中不合理儿童药品处方19张(9.55%)。结论:该院产科2022年仍存在不合理使用中成药情况,医院需及时采取积极的干预措施,以保障产科用药规范合理,保障患者的安全。

某三级甲等医院人工智能辅助医药领域专利申请及授权现状分析

目的促进医院人工智能(AI)辅助医药领域相关专利的发展。方法利用解决方案式全球专利智能检索分析平台(HimmPat)提供的专利检索及分析功能,检索某三级甲等医院(截至2023年10月31日)涉及AI辅助医药领域的相关专利数据,分析该领域专利的申请和授权情况、申请法律状态、授权专利类型、具体技术领域、合作申请情况等。结果该院共申请专利130件,其中38件(29.23%)获得授权;16件(12.31%)为合作申请专利,授权率为50.00%。2017年开始出现相关专利申请,之后申请量呈先逐年增加后下降又回升趋势,授权量自2021年起迅速增长;在审专利申请有56件(43.08%),失效专利申请较多(36件,27.69%);获授权专利中发明专利占比较大(34件,授权率为26.98%),实用新型专利授权仅4件。具体技术集中在智能诊疗和智能健康管理领域。结论该院AI辅助医药领域相关专利申请量保持增长态势,但还存在专利管理人才缺乏、涉及技术领域单一、合作申请少等问题。建议医院巩固智能诊疗和智能健康管理方面的专利申请,加强专利管理人才队伍建设,建立高价值专利培育体系,规范医疗数据标准,培养复合型人才,深化与企业合作,并推动专利转化及在高附加值的AI辅助药品研发方面的研究。