我国已上市治疗用提取分离类和菌体制剂类产品分析

目的：分析我国已上市治疗用提取分离类和菌体制剂类产品存在的差距,明确努力方向。方法：基于我国已上市治疗用提取分离类和菌体制剂类产品批准数据进行统计分析和对比分析。结果：对我国已上市治疗用提取分离类产品中的血液制品和多组分生化药物以及菌体制剂类产品的批准数量、企业数量进行了梳理,并与FDA批准情况进行对比分析。结论：治疗用提取分离类和菌体制剂类产品都是早期的治疗用生物药物,血液制品目前仍发挥着重要的临床价值,但重复申报情况严重。多组分生化药物和菌体制剂重复申报情况很少,但在临床上应用很少。FDA批准的两类产品数量较少。     

我国已上市治疗用单抗类产品分析

目的：分析我国已上市治疗用单抗类产品存在的差距,明确努力方向。方法：基于我国已上市治疗用单抗类产品批准数据进行统计分析和对比分析。结果：对我国单抗类药物的发展历程、上市时间、批准品种以及我国已批准上市的单抗类药物与FDA单抗类药物的批准情况进行了对比梳理。结论：单抗类药物在生物技术制药中占有重要地位,并逐渐成为生物医药领域发展的主要方向。我国单抗类药物中国产品种与进口品种存在差距,整体上与FDA存在差距。但随着近年来的改革,发展潜力及势头良好。     

我国已上市治疗用生物制品整体情况分析

目的：梳理我国已上市治疗用生物制品的整体情况,提炼出存在的问题,为行业提供参考信息,同时为完善我国治疗用生物制品注册管理制度体系提供数据支持。方法：基于我国已上市治疗用生物制品的数据,进行统计分析和对比分析。结果：对我国已批准治疗用生物制品信息进行了整合,并从批准上市产品的发展历程、创新程度、技术类别等不同维度进行了全方位深入分析。结论：与发达国家相比,我国治疗用生物制品的研发和产业化相对较晚,市场规模较为有限,但增速显著高于全球水平。     

我国已上市治疗用生物制品问题分析及监管建议

目的：对我国已上市治疗用生物制品现状及存在问题进行分析,并在此基础上从鼓励创新、系统构建注册法规等多个角度提出完善监管的建议。方法：基于对我国已上市治疗用生物制品批准情况的深度分析,通过专家咨询,提出建议。结果：治疗用生物制品产业发展迅速,在一定程度上满足了我国公众临床用药的需求,但仍与国际先进水平存在较大差距。结论：从鼓励创新、促进生物类似药发展、完善药品批准文号等方面提出建议。     

美国紫皮书制度研究与构建我国“生物制品已上市产品目录集”必要性及可行性探讨

目的：对美国FDA紫皮书制度进行研究，结合我国生物制品监管现状与发展，探讨构建我国"生物制品已上市产品目录集"的必要性和可行性。方法：文献研究和对比研究法。结果：对美国紫皮书的内容和作用、美国紫皮书的制度支持及其关键要素进行了研究，在此基础上分析我国"生物制品已上市产品目录集"构建的必要性和可行性。结论：我国现阶段构建"生物制品已上市产品目录集"已具备一定的实施基础，具有可行性和必要性。     

试析民族药品种上市后的再研究

目的：探讨已上市民族药品种的再研究路径。方法：对已上市民族药品种的临床、药学及药理毒理研究情况进行分析。结果与结论：民族药品种的上市前研究因科学发展水平、监管历史、民族政策等原因存在诸多先天不足,有必要进行上市后再研究;研究应先理清存在的关键性问题,再结合品种实际特点,在民族医药理论的指导下分阶段开展。     

小鼠Metrnl单克隆抗体的制备及鉴定

目的 制备抗小鼠Metrnl单克隆抗体,并进行初步筛选鉴定。方法 分别制备小鼠Metrnl多肽片段和全长蛋白作为免疫小鼠抗原,取免疫后小鼠脾细胞与SP2/0骨髓瘤细胞融合,筛选阳性杂交瘤细胞,并亚克隆获得稳定细胞株,制备腹水。用ELISA方法检测腹水抗体效价;用Western blot方法鉴定抗体。结果 由14种多肽抗原制备的56株单克隆抗体中,未筛选出可用于Western blot识别Metrnl的抗体;由全长蛋白制备的25株抗体中,有12株可识别Metrnl蛋白。结论 本实验成功制备了12株单抗,可用于识别检测小鼠Metrnl蛋白。     

广东省已上市中药制剂备案变更常见问题分析与建议

目的：为我国已上市中药制剂备案变更提供指导与建议。方法：通过整理2023年广东省已上市中药制剂备案变更的受理审评情况,分析持有人申报变更存在的问题及其主要原因,从变更的事前事中事后提出可行建议。结果与结论：对213个已上市中药制剂备案变更品种进行梳理,发现持有人在备案变更方面主要存在申报程序不合规、备案内容不标准、研究验证不充分的问题。建议持有人变更前合理确立变更事项、变更时科学开展研究验证、变更后持续关注风险管理,提升中药制剂备案变更的能力。     

我国药品加快上市注册程序的注册情况分析

目的：对2020年新修订的《药品注册管理办法》颁布前后我国纳入药品加快上市注册程序并已批准上市的药品信息进行分析,为完善我国药品加快上市注册程序提供参考。方法：检索国家药品监督管理局药品审评中心发布的2019-2021年度药品审评报告,对通过优先审评和药品加快上市注册程序而上市的相关药品数据资料进行信息整理和汇总分析。结果：通过药品加快上市注册程序的上市药品数量逐年增多,优先审评审批资源向临床优势药品和创新药品倾斜。结论：药品加快上市注册程序可为临床价值显著的药品提高审批效率,在一定程度上激发制药企业研制热情,但药品加快上市注册审批体系仍需进一步完善配套政策,细化实施要求,加快专业指南出台,鼓励以临床价值为导向的药品的研发创制, 不断提升药品监管部门的服务和监管能力。     

精蛋白锌重组赖脯胰岛素混合注射液治疗初发2型糖尿病的疗效及安全性观察

摘 要 目的：比较精蛋白锌重组赖脯胰岛素混合注射液与精蛋白锌重组人胰岛素混合注射液治疗初发2型糖尿病的疗效及安全性。方法: 初发2型糖尿病患者49例随机分为观察组和对照组。2组患者均给予常规饮食治疗及健康教育。观察组餐前皮下注射精蛋白锌重组赖脯胰岛素混合注射液 ,对照组餐前皮下注射精蛋白锌重组人胰岛素混合注射液。治疗2周后,比较两组患者的空腹血糖（FBG）、餐后血糖(PBG)、糖化血红蛋白（HbA1c）、血糖达标时间、低血糖发生率。结果: 治疗后,两组患者FBG、PBG 、HbA1c均较治疗前显著降低（P<0.05）,但2组间FBG、PBG、HbA1c比较差异无统计学意义（P>0.05）。观察组低血糖发生率低于对照组,血糖达标时间短于对照组（P<0.05）。结论:精蛋白锌重组赖脯胰岛素混合注射液治疗初发2型糖尿病血糖达标快,安全性高,优于精蛋白锌重组人胰岛素混合注射液。     

Emerging delivery platforms for mucosal administration of biopharmaceuticals: a critical update on nasal,pulmonary and oral routes

Introduction: Protein and peptide-based drugs are preferred therapeutics due to their specificity but are mainly administered by injection. Alternative routes for peptide delivery are preferred because of their ease of administration and increased patient compliance.

Areas covered: This review provides a critical overview of current strategies for non-invasive mucosal delivery routes of therapeutic proteins and peptides, with emphasis on their advantages and limitations. Selected new trends and interesting novel formulations in advanced preclinical and clinical development stages for the pulmonary, nasal and the oral route are discussed for the most relevant peptide and protein drugs in terms of their specific requirements and intended therapeutic applications.

Expert opinion: Despite the low frequency of clinical breakthroughs with non-invasive routes, these remain an active research area not only due to their improved therapeutic potential, but also due to the attractive commercial outcomes they offer. Currently, a number of technologies are adopted, including combinations of penetration enhancers with protease inhibitors and/or nanotechnology-based products and a few candidates are anticipated to be approved in the near future.     

Oral peptide and protein delivery: intestinal obstacles and commercial prospects

Introduction: Pharmaceutical research and development is increasingly focussed on biopharmaceuticals including peptide and protein drugs. Despite their growing importance and almost 100 years of research, the vast majority are still only available by injection. Oral bioavailabilities of peptide and protein drugs are very low mainly because of the stability and permeability barriers of the gastrointestinal (GI) tract.

Areas covered: Data from studies of peptide/protein drug oral bioavailability, stability and permeability in the stomach, small intestine and large intestine have been compiled to make comparisons between the various regions of the GI tract and peptides/proteins with differing characteristics. Assessment of the oral formulation strategies that have progressed farthest in clinical trials has been conducted to identify which have the best potential for future success.

Expert opinion: Oral delivery of peptides and small proteins is increasingly achieved by utilising formulations that combat the stability challenges of the GI tract and disrupt the intestinal cell membranes to enable absorption. However, oral bioavailabilities remain low and variable therefore high, potentially toxic doses of peptide/protein drugs are needed to elicit a therapeutic effect leading to high cost of the final product. There is very little research into larger proteins, making their oral delivery unlikely in the near future.     

新发传染病相关的药品技术战略储备思考

目的： 对新发传染病相关的药品技术战略储备进行探讨,旨在为战胜此次新冠肺炎疫情,更为下一次可能的疫情做好准备。方法： 梳理了世界卫生组织、欧盟、美国对与公共健康威胁相关的药品技术储备情况,主要阐述了新发传染病相关的疫苗技术储备信息,给出WHO建议的新型冠状病毒肺炎（COVID-19）药品研发信息,EMA在公共健康威胁（例如大流行性流感）相关药品方面的技术储备情况,并总结了EMA对大流行防备疫苗的技术要求。结果与结论： 建议在我国建立由国家主导并投资的与公共健康威胁相关的预防用疫苗或治疗用药物的技术和产品战略储备,例如为新发传染病的疫苗开发制定清晰的计划、法规和程序。药品技术和产品的战略储备可包括：1）政府部门制定与公共健康威胁相关疾病的清单,例如可能引起重大流行病的突发疾病用药优先研发清单;2）审评审批方面可考虑制定大流行性疾病疫苗（包括大流行防备疫苗）、大流行性疾病治疗药物研发的技术要求,涉及质量、非临床、临床、申报程序等内容;3）通过国家科技立项等方式投资预防用疫苗及治疗用药物的研制;4）引导生产企业进行相关的药品战略储备。     

Inhibition of aggregate formation as therapeutic target in protein misfolding diseases: effect of tetracycline and trehalose

Importance of the field: The identification of molecules that inhibit protein deposition or reverse fibril formation could open new strategies for therapeutic intervention in misfolding diseases. Numerous compounds have been shown to inhibit amyloid fibril formation in vitro. Among these compounds, tetracycline and the disaccharide trehalose have been reported to inhibit or reverse amyloid aggregation but their efficiency as potential drugs is controversial.

Areas covered in this review: The results obtained using tetracycline and trehalose, reported in the last 15 years, are described and discussed.

What the reader will gain: The conclusions have important implications for the development of therapeutic agents for protein deposition diseases. If fibrillar proteins contribute to cell degeneration, then the disassembly of fibrils may reverse or slow down disease progression; however, if the action of therapeutic agents produces intermediates of fibrillation and/or products of fibril disaggregation, then their accumulation could be harmful.

Take home message: Care should be taken to ensure that strategies aimed at inhibiting fibril formation do not cause a corresponding increase in the concentration of toxic oligomeric species.     

Patent Evaluation: Human Amyloidin Protease as a Potential Therapeutic Agent

Summary

Novelty: The purification of human amyloidin protease, the generation of antibodies specific for the enzyme, and the isolation and in vitro expression of its cognate gene, are reported.

Biology: Methods for the purification of amyloidin protease from human tissue are provided. The enzyme has an appparent molecular weight of 80 kDa and proteolytically cleaves a Met-Asp peptide bond in the amyloid precursor protein which releases the mature Asp terminus of the β-amyloid peptide. An assay for inhibitors of the protease is described, and antibodies raised against the enzyme are provided. The isolation and characterization of the cognate gene is described together with methods for expressing the recombinant protein in vitro. Inhibitors of the enzyme may have use for the therapeutic intervention of Alzheimer's disease, and antibodies raised against it may have diagnostic use.