ľ���׾���ѧ�ɷ��о�(��)

??OBJECTIVE To study the chemical constituents of Fomes fomentarius (L.Ex.Fr.). METHODS The compounds were isolated by chromatography on silica gel column, Sephadex LH-20 column, and their structures were elucidated by spectral analysis. RESULTS Six compounds were obtained and identified as fomentarinin (1), 2-hydroxy hexacosanoic acid ethyl ester (2),syringic acid (3), syringyl alcohol (4), vanillin (5), and ergosta-7,22-diene-3,6-dione (6), respectively. CONCLUSION Compound 1 is a new compound, and compound 2-6 are isolated from the fungus for the first time.
     

ɳ����͡����2�����򲡵�ҩ�ﾭ��ѧϵͳ����

??OBJECTIVE To systematically evaluate the economics of saxagliptin for treatment of type 2 diabetes mellitus. METHODS PubMed, Embase, Cochrane Library, NHS EED, CNKI, Wanfang and CBM were systematically searched. Literatures were screened according to pre-defined inclusion criteria. The quality of included studies were evaluated by CHEERS statement and the economic RESULTS were systematically analyzed. RESULTS Eight cost-effectiveness analyses were included, one of which was conducted in China. Patients among the studies all had blood glucose non-adeguately controlled by monotherapy. When added on to metformin, saxagliptin was cost-effective compared with sulfonylureas (glipizide and glimepiride) and thiazolidinediones (pioglitazone and rosiglitazone). When added on to metformin or sulfonylureas, saxagliptin was cost-effective compared with NPH insulin. CONCLUSION Saxagliptin represents a cost-effective option in treatment of type 2 diabetes mellitus patients with non-adequately controlled blood glucose after monotherapy.     

ҩƷ�ٴ���ֵ����ָ����ϵ�Ĺ����о�

??OBJECTIVE To analyze the connotation and composition of the clinical value of drugs, and to build the index system for the evaluation of drug's clinical value, hence to provide references for its scientific evaluation. METHODS We designed the preliminary constructs index system referencingmedicine clinical evaluation indicatorsof German and French firstly. And then the expert interview and Delphi survey were used to analysis to determine the index system and index weight of medicine clinical evaluation. RESULTS The classified index system of the clinical value was established, which was composed of 2 first-grade indexes including clinical value and innovation value and 15 grade two indexes. Experts were invited to assess the value ranking according to the background information of rosuvastatin, atorvastatin and simvastatin statin drugs by their generic names. The expert's scoring results were summarized to determine the sequence. And it were compared with the average market prices in Germany, France, Britain, the United States, South Korea, Japan and analyzed. CONCLUSION The clinical value of drugs is an international standard for determining the reasonable price of drugs. This research method is feasible to determine the drug prices sequencing by the classified clinical value of drugs in the same kind of product. The price sequencing of some generic names of statin drugs did not correspond with its clinical value sequence, and the price can not reflect its value. The integrity and authenticity of the background data directly determine the classification of the clinical value. Various parties are needed to participate in providing detailed data and information.     

�ƾ���ֲ����о���չ���俪��ǰ��

??Polygonati Rhizoma as one of the most common Chinese herbal medicine and food was widely distributed in China. In TCM clinic, it was used for diabetes, hyperlipemia and rehabilitation therapy of cancer. Nowadays, with the rapid development of health industry, Polygonati Rhizoma shows excellent functions on healthcare, and then a surge of demands was coming. But there are so many species belongs to this genus and the classification criteria are not unified, so some important problems become urgently to be resolved, such as how to guarantee the quality and how to keep sustainable development. In this paper, the origin, distribution in China, chemical composition, pharmacological, and clinical application are reviewed. Its prospect is discussed to be helpful to promote the comprehensive development of Polygonatum.     

���򲡺ϲ���������ʹ�ð��������뻪�����໥���÷���

??OBJECTIVE Blood tends to deposit in atrium to form thrombus in patients with atrial fibrillation. Patients with diabetes are in high coagulation state, for whom thrombosis is easy to occur. The number of diabetic patients with atrial fibrillation is large. Warfarin is one of the most widely used oral anticoagulants, which can cause major or fatal bleeding, so it is necessary to perform regular monitoring of international normalized ratio (INR) on all patients treated with warfarin. New kinds of antidiabetic drugs are widely used in clinic, among which a lot affect INR levels achieved with warfarin therapy. Clinical pharmacists should pay attention to drug interactions and monitor adverse drug reactions. As a new antidiabetic drug, exenatide has less reports of interaction with warfarin. The characteristic of the interaction between exenatide and warfarin was investigated, with the aim to optimize the rational and individualized medication. METHODS A case was introduced in which exenatide was administrated combined with warfarin, so that the possible mechanism of exenatide affecting to warfarin were analyzed. RESULTS INR declined from 2.13 to 1.57 after exenatide being added, and decreased further to 1.43 with concurrency of the increasing exenatide dose. On the contrary, INR was on rise as result of discontinuing exenatide. At last, INR returned to 1.78 when the patient discharged. CONCLUSION Exenatide inhibited the absorption of warfarin, which lead to INR decline attributed to its effect of slowing down the gastric emptying. When exenatide and warfarin are combined,the dose of warfarin must be adjusted based on INR under clinical monitoring.     

�����⺱���������о���չ�Աȷ���

??OBJECTIVE To study and collate the literature on rare diseases in domestic and abroad, and comparative analysis, provide a scientific basis for the domestic rare diseases research. METHODS Retrieved the Web of Science, China National Knowledge Infrastructure from January 2011 to June 2016 published literature about rare diseases. RESULTS Through the screening of literature, finally determine the 200 articles for analysis. It is divided into seven research directions:rare diseases policy research, rare diseases legal and regulatory research, rare diseases medical social security study, orphan drugs availability research, orphan drugs economic evaluation study, orphan drug development research, rare diseases defined standard research. CONCLUSION Rare diseases policy research is the focus of research both domestic and abroad. Compared with foreign countries, the domestic research on the availability and economic evaluation of orphan drug is less, especially the economic evaluation research is almost blank. It is suggested that the researchers study the multiple aspects of rare diseases and drugs, and to provide the basis and reference for build rare disease policy in China.In addition to the field of rare diseases research, rare diseases drugs face many difficulties in pharmaceutical research, production and supply.The precondition to solve these problems is the nation formulate specific policies and regulations for rare diseases,and then clear the official definition standards of rare diseases,establish relevant policies to encourage pharmaceutical companies to develop rare diseases drugs.     

�����ʶ���������ĺϳɼ������������о�

??OBJECTIVE To synthesize 5-substituted indole-3-deoxypodophyllotoxin derivatives and study their antitumor activity. METHODS The target compounds were synthesized through a series of reactions and their anti-tumor activity in vitro were evaluated against Hela, K562 and K562/A02 cell lines by MTT as assay. RESULTS Ten target compounds were synthesized and confirmed by ¹H-NMR, ¹³C-NMR, and HR-ESI-MS. All the target compounds had different degrees of cytotoxic activity in vitro. Most of the compounds had significant anti-MDR activity in vitro. CONCLUSION 5-Substituted indole-3-deoxypodophyllotoxin derivatives have good antitumor activity and worth of further study.     

ɳ����͡�Ͱ������Ķ������Թ������ɴ������ʹǵ�Ӱ��

??OBJECTIVE To determine the effects of saxagliptin and exenatide on humerus cancellous bone of diabetes-induced osteopenia rats by histomorphometry. METHODS Thirty-five Cases of female SD rats were randomly divided into normal group (N group, n=7), control group (C group, n=7), and the remaining rats were used to establish the type 2 diabetic model by combination of high-fat&sugar-diet feeding for 4 weeks and then low-dose streptozotocin injection(STZ, 30 mg??kg^-1) . After 10 d, the oral glucose tolerance test and the fasting blood glucose were measured, rats with high OGTT(2 h) above 11.1 mmol??L^-1 and high FBG above 16.7 mmol??L^-1 were divided into model group (M group, n=5), saxagliptin group (G group, n=5) and exenatide group (D group, n=6), and continuously treated for 30 d. The left humerus (proximal humeru metaphometry, PHM) were fixed with 4% paraformaldehyde for 48 h, uncalcified embedded in methyl methacrylate after dehydrated and cleared, and sections were taken for bone histomorphometry after Masson-Goldner Trichrome stained. RESULTS In PHM, there was no statistical significance between N and C group, the trabecular bone area ratio( BV/TV) and trabecular quantity were significantly decreased (P??0.01) in M group, while the trabecular separation degree was increased, comparing with those in C group (P??0.01), and the trabecular bone area ratio( BV/TV) and trabecular quantity in G and D group were higher (P??0.01) than those of model rats, while the trabecular separation degree was decreased, comparing with those in M group (P??0.01). Cell parameters showed no statistical significance between N and C group, the osteocllast number and percentage of osteocllast surface perimeter were significantly reduced(P??0.05, P??0.01) in M group, while the osteoclast number and percent osteocllast surface perimeter were significantly increased (P??0.01) as compared with those in C group, saxagliptin and exenatide were found to significantly induce osteocllast number (P??0.01) and percentage of osteoblast surface perimeter (G group P??0.05, D group P??0.01), while reduce osteoclast number (P??0.01) and percent osteoblast surface perimeter (P??0.05) compared with M group. In growth-plate, there was no statistical significance between N and C group, the thickness of growth-plate and the diameter of the mast cells were reduced in M groups (P??0.01), while the thickness of growth-plate (P??0.01) and the diameter of the mast cells (P??0.05) were increased in G and D group,compared with M group. CONCLUSION Therapeutic effects of saxagliptin and exenatide on diabetes -induced osteopenia rats was showed, and the mechanism may be related to the improved growth rate of growth-plate and the changed bone turnover status.     

微/纳米口服结肠靶向给药系统在炎症性肠病治疗中的研究进展

口服结肠靶向给药系统(OCTDDS)被设计用于将治疗剂靶向递送至结肠疾病部位,以改善药物治疗效果,降低全身不良反应,提高生物利用度,对于炎症性肠病(IBD)的治疗十分有利。然而,疾病状态下,胃肠道的生理环境改变会影响药物的治疗功效。临床常用的治疗IBD的药物长期服用会导致严重的全身性不良反应,中药作为其补充和替代药物,吸引了越来越多研究者的关注。近年来,微米和纳米颗粒因其相对适宜的粒径、较长的药物滞留时间、可控的药物吸收率等优势,逐渐成为治疗IBD的有效工具,文章主要综述影响药物口服递送的胃肠道生理因素,微/纳米制剂的剂型设计和药效作用研究进展,旨在为口服生物利用度低的药物的结肠靶向递送提供参考。     

�������ε�pH����֬�����о���չ

??As one of drug or gene carriers, peptide-modified pH-sensitive liposomes can actively target the tumor tissues, release anti-tumor drugs in specific areas, reduce side effects of drugs, and improve their therapeutic potency. In this review, the modification methods of peptide-modified liposomes and their anti-tumor applications by gene transfection and drug delivery are introduced. This paper is expected to provide a reference for the preparation of peptide-modified pH-sensitive liposomes and design of carriers for anti-tumor drugs.     

介孔二氧化硅纳米粒在抗肿瘤药物靶向给药系统中的应用

化学疗法是治疗癌症的主要疗法之一,但传统抗肿瘤药在体内呈全身性分布,肿瘤组织内很难达到有效药物浓度,且自身又不具备辨别正常细胞与肿瘤细胞的能力,易造成全身毒性反应,已远远不能满足临床需要。近几年,随着纳米技术的发展及普遍应用,纳米靶向抗肿瘤药物的研究取得了突破性的进展,其中介孔二氧化硅纳米粒(MSNs)在抗肿瘤药物靶向给药系统中的研究日益增多,因其特有的结构及理化特征,具有作用于特定靶点,直接抑制肿瘤细胞的生长,减少对正常细胞和组织器官的毒副作用,可以长期用药等优点,有望成为抗癌药物的优良载体,对MSNs在癌症治疗领域的应用也已成为现在医药领域的研究热点。该文对2008—2015年MSNs在抗肿瘤药物靶向给药系统的最新研究作一综述,分别介绍了MSNs在抗肿瘤药物被动靶向、主动靶向、物理或化学条件响应型靶向及其他复合靶向给药系统中的应用,以期对目前具有良好抗肿瘤作用的化药、天然药物及中药单体化合物的减毒增效及进一步开发提供参考。     

中药活性成分口服结肠靶向纳米系统治疗溃疡性结肠炎的研究进展

溃疡性结肠炎(ulcerative colitis,UC)为现代常见病、难治病。因其发病反复,临床常需反复长期使用柳氮磺胺吡啶、免疫抑制剂等药物,但其疗效有限且易产生不良反应。现代研究发现中药多酚类、生物碱类、醌类、萜类等活性成分通过多靶点机制,表现出较好缓解UC的作用,且不良反应相对较低,但存在水溶性差、胃肠道不稳定和结肠靶向性差等制剂学问题。针对以上制剂学问题,研究者构建了多种中药活性成分的口服结肠靶向纳米系统,通过避免胃肠道破坏、延长肠滞留、实现药物在病灶部位控释等方式显著提升了对UC的治疗效果。对具有UC防治作用的中药活性成分及其作用机制,以及口服结肠靶向纳米系统用于UC治疗的研究进展进行综述,以期为中药活性成分口服靶向治疗UC提供思路。     

碳纳米管的载药及安全研究进展

对碳纳米管的载药进行文献整理和分析。查阅近8年来国内外相关文献39篇。研究发现,近年来,随着药学、生物学和材料学等多学科的交叉渗透发展,人们渐渐意识到新型载药材料的应用对药物的研究具有非常重要的促进作用。碳纳米管(carbon nanotubes,CNTs)具有独特的管状结构,可有效负载和递送药物,被巧妙地用于构建独具特色的药物传输系统。虽然CNTs的载药(特别是中药)研究国内外还少见报道,但实践证明,通过表面化学修饰等手段,制备溶解性好、低毒性的功能化CNTs作为药物载体,在抗肿瘤等领域具有很好的应用前景。作者概述了近年来CNTs的载药研究(如阿霉素、盐酸表柔比星、地塞米松、两性霉素B和中药有效成分异甘草素等)及生物安全研究(包括组织毒性研究和细胞毒性研究)进展,并对CNTs的中药载药应用作了展望,以期为更多安全、可控、有效的新型递药系统的研发及相关疾病的临床治疗提供参考。     

基于糖基化修饰的靶向药物传递系统研究概况

近年来,基于药物受体及转运体介导的靶向药物传递系统已被广泛研究,靶向药物传递系统增强药物在病变部位的浓度和疗效,最大限度地降低了药物毒副作用。人体不同细胞表面高表达的特异性凝集素受体及脑毛细血管内皮细胞、肿瘤细胞高表达的葡萄糖转运体亚型Ⅰ,可与其相应的糖基配体产生特异性识别。将糖基配体分子如甘露糖、半乳糖、葡萄糖等,键接在药物传递系统上,可赋予其靶向性。这些糖基配体具有无毒、无免疫原性、生物相容性和生物可降解性良好等诸多优点,可广泛用于对药物传递系统的糖基化修饰。本文综述了近5年来糖基化修饰药物传递系统的靶向机制、合成方法及靶向特性,并对其发展前景作了展望。     

ҩ���лø�������ͽ鵼�Ŀ�����ҩ���ٴ����Է�Ӧ�о���չ

??Antitumor drugs have the characteristics of low therapeutic index, narrow safety window, and so on, which are prone to have toxic and side effects in the course of clinical therapy, thus limiting their use. In recent years, some studies have pointed out that the mechanism of adverse reactions of antitumor drugs is related to drug metabolism enzymes, receptors and transporters. Among them, drug metabolism enzymes and their gene polymorphisms play an important role in the toxic and side effects of antitumor drugs. In this paper, we analyze and summarize the side effects of antitumor drugs mediated by drug metabolism enzymes, mainly from the aspects of the roles of metabolic enzymes and their gene polymorphism in the metabolic activation and metabolic detoxification of antitumor drugs, in order to effectively avoid or reduce the toxic side effects of antitumor drugs, and to provide a reference for individualized treatment of cancer.     

基于刺激响应及靶向因子修饰载多烯紫杉醇纳米递送系统的研究进展

多烯紫杉醇是天然抗肿瘤药物紫杉醇的衍生物,具有广谱、高效的抗肿瘤活性,但其溶解性低、组织分布广,限制了临床应用。刺激响应型纳米递送系统凭借其载体材料结构的多元性、环境敏感释药性,有效改善了多烯紫杉醇这些缺陷,在此基础上,修饰靶向因子可使药物靶向递送,改变药物的组织分布,进一步提高抗肿瘤效果。综述近年多烯紫杉醇刺激响应型及靶向因子修饰纳米递送系统的研究进展,提出其发展面临的挑战及未来趋势等关键问题,以期为多烯紫杉醇在抗肿瘤药物的研究开发方面提供参考。     

多发性硬化的药物治疗研究进展

多发性硬化（MS）的药物治疗方案近年来发生了显著的变化：从作用于全身副作用较大的激素类药物发展为针对特定免疫细胞的靶向药物;从经SC、im或iv等非肠胃途径给药发展为方便的口服药物。在诸多治疗方案中,免疫调节类药物、神经保护类药物和干细胞移植疗法目前在临床上占主导地位。随着对MS病理学研究的发展,免疫调节类药物已逐步被人们所认识。按免疫调节类药物直接靶向的免疫细胞的不同对药物进行分类,对药物的作用特点、临床使用情况、毒副作用等进行综述,同时对神经保护剂和干细胞移植疗法做简要阐释。     

基于天然多糖构建纳米药物递送系统的研究进展

天然多糖来源广泛,是一类具有良好生物活性、生物相容性和生物可降解性的天然高分子材料,由于其亲水性好、荷电性、易被化学修饰等特殊性质,近年来基于天然多糖作为纳米递送载体参与构建纳米递送系统或以新型纳米递送载体搭载天然活性多糖提高纳米药物递送靶向性和疗效的研究工作在生物医药领域深受科学家们关注,已成为当前纳米药物研发的一个重点发展趋势。笔者整理国内外相关文献,对天然多糖作为纳米递送载体的制备原理与方法进行了阐述,并按真菌多糖、植物多糖、动物多糖、细菌多糖和藻类多糖等不同来源多糖进行分类,分别选取代表性研究实例对天然多糖构建纳米药物递送系统的研究进展进行了归纳和总结。