中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

基于中医古籍文献的升降散应用溯源及探析

通过对中医古籍中有关升降散论述的文献梳理,全面探讨其内涵。本方是在大黄、僵蚕为雏形的基础上增加蝉蜕、姜黄而成方,几经易名,终在杨璿《伤寒瘟疫条辨》中为后人所熟知。本方广泛用于治疗瘟疫,以丸剂、散剂为主,方便携带,便于服用;重用大黄旨在祛邪、逐秽;应用时视人之体质强弱和量其毒之轻重而判断用药多寡,并辅以米酒、生蜜等以顾护正气。杨璿将其由治疗“热疫”的专方扩展为治疗“表里三焦大热”的通用方剂,扩大了本方治疗疾病范围。     

Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From the KEYNOTE-028 and KEYNOTE-158 Studies

IntroductionPembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC.MethodsEligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)–positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review.ResultsEighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n = 19; KEYNOTE-158, n = 64) were included. Median follow-up duration was 7.7 (range, 0.5–48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4–29.4); two patients had complete response (one with a PD-L1–positive tumor), and 14 patients had partial response (13 with PD-L1–positive tumors). The median duration of response was not reached (range, 4.1‒35.8+ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events.ConclusionsPembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.     

干扰素在恶性淋巴瘤自体移植后早期干预的应用

目的:观察非霍奇金淋巴瘤（non-Hodgkin's lymphoma，NHL）患者自体造血干细胞移植（autologous hematopoietic stem cell transplantation，ASCT）术后应用重组人α-2b干扰素（α-2b IFN）进行早期干预治疗的临床疗效。方法:选取18例行ASCT的NHL患者为研究对象，移植前疾病评估均未达到完全缓解（complete remission，CR），试验组血象恢复后给予IFN 3 000 000 U次/隔日干预治疗，3个月后停用；对照组未行干扰素干预治疗，分析总体疗效及两组对比的生存情况。结果:随访中位时间为34（10~50）个月，患者中位生存时间为37（31~45）个月，3年总体无进展生存（progressive free survival，PFS）、总生存（overall survivial，OS）分别为54.7%、66.8%。ASCT后试验组1年内无疾病复发，2年内复发率为12.5%；对照组1年内复发率为20%，2年内复发率为30%。结论:NHL患者在ASCT后给予重组人α-2b IFN早期干预治疗，患者耐受性好，可能降低移植后早期复发率。     

Oral Dispersible System: A New Approach in Drug Delivery System

Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day''s more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form.