糖尿病治疗药的现况和今后发展方向

将治疗糖尿病的药物分类为胰岛素类 ,胰岛素分泌促进剂 ,胰岛素增敏剂 ,一氧化氮合酶抑制剂 ,糖原异生抑制剂 ,影响碳水化合物吸收的药物 ,中药类等类别分别进行综述 ,并指出今后发展方向。对今后中药的发展提出了看法。     

糖尿病治疗药的现况和今后发展方向

将治疗糖尿病的药物类为胰岛素类，胰岛素分泌促进剂，胰岛素增敏剂，一氧化氮合酶抑制剂，糖原异生抑制剂。影响碳水化合物吸收的药物，中药类等类别分别进行了综述，并指出今后发展方向。对今后中药的发展提出了看法。     

糖尿病治疗药的研究进展

糖尿病是由于体内胰岛素绝对或相对不足所致的一种内分泌代谢性疾病。随着对糖尿病基础理论的研究深入,目前临床用药已打破了传统的磺酰脲类、双胍类等化学结构,新型药物相继开发,本文介绍糖尿病治疗药ＡＴＰ敏感钾α２－肾上腺素受体拮抗剂、噻唑烷二酮类胰岛素增敏剂、β２－受体激动剂、改善脂肪酸代谢的药物、有机氧钒化合物、α－葡萄糖苷酶抑制剂、一氧化氮合酶抑制剂等的最瓣进展,概述这些药物的结构类型、作用特点和构效     

老药新用治疗糖尿病

近年发现一些非传统治疗糖尿病药物有一定降血糖作用，且对控制并发症有益，现综述如下。1．芬氟拉明（Fenfluramine）该药为常用减肥药物，近年发现有降血糖作用。张达奇等观察45树非胰岛素依赖型糖尿病（NID－DM）患者，单服该药第1周起血糖降低，至第12周时血糖达最低水平。     

中西医药治疗糖尿病的发展进程

糖尿病是一种复杂的、多层面、多网络、多器官损伤的疾病。对付这种疾病,一种方法很难解决问题。所以,我们提倡中西医结合治疗糖尿病。中医辨证论治加用中药或滋阴补气,或活血化瘀巩固机体内环境如阴阳、气血、升降等机制相对调整,对原有剂量的西药降糖药往往更为敏感,而依具体情况可以减少西药用量。     

新型糖尿病治疗药罗格列酮的合成

以2－氯吡啶为起始原料,先合成4－[2-(甲基－2－吡啶氨基）乙氧基]苯甲醛,然后与2,4－噻唑烷二酮缩合,氢化制得罗格列酮,并对反应条件进行了优化,以2－氯吡啶计总收率为36．2％,实验结果表明：该路线具有原料易得,收率高等优点,适合工业化生产。     

城乡结合部社区糖尿病现况与综合治疗的探讨

目的调查分析城乡结合部社区糖尿病现况及综合治疗效果。方法收集城乡结合部社区74例糖尿病患者的病例资料,分析74例患者血糖测量、体质量控制、糖尿病并发症发生情况;将37例患者设为观察组进行综合治疗,另外37例患者设为对照组,给予常规药物治疗,观察治疗效果。结果 74例患者中仅有40.54%的患者会使用血糖仪自测血糖;55.41%的患者体质量超过正常值;58.11%的患者伴有不同程度的并发症;观察组治疗前后空腹血糖、餐后2h血糖变化幅度大于对照组(P<0.05)。结论综合治疗是社区糖尿病患者的有效治疗方法,其能有效增强患者对糖尿病知识的了解,改善患者生活。     

糖尿病周围神经病变的药物治疗现况

糖尿病周围神经病变（diabetie peripheral neuropatby，DPN）是常见的糖尿病微血管慢性并发症之一，英国糖尿病前瞻性研究发现超过11％的患者在糖尿病确诊的同时就已经存在明显的DPN。由于DPN累及神经部位不同，DPN的定义、诊断标准、判定方法的不同，且临床表现差异很大，其真正的发病率难以准确估计，造成文献报道DPN发病率分别为10％～90％不等，     

Utilisation of drugs for diabetes mellitus

This article reviews the data from drug utilisation research on antidiabetic agents, oral hypoglycaemics and insulin. Study methods specific to this type of pharmacoepidemiological research are discussed and critiqued. A brief overview of the sources of drug utilisation data is presented, followed by a review of specific pharmacoepidemiological investigations. We evaluate the usefulness of these studies in assessing true drug consumption, in evaluating comorbidity in diabetic patients and in measuring the prevalence of diabetes. International comparisons of antidiabetic drug utilisation, also reviewed and analysed, demonstrate wide variations in the use of hypoglycaemic agents, which have arisen for reasons which are unclear. Drug utilisation research thus far has been limited by the paucity of studies relating these variations in antidiabetic drug use to specific clinical outcomes. There is a need to expand the applications of research on the use of antidiabetic agents, including assessment of patterns of morbidity across geographic boundaries and over time.     

Current status of and future perspectives for platinum antitumor drugs

Cisplatin, a simple inorganic compound, has been one of the leading antitumor drugs for near 30 years. However, cisplatin has several drawbacks such as toxicity and drug resistance. Therefore, much attention has been focused on the development of new platinum complexes with improved pharmacological properties and a broader spectrum of activity to tumors. The recent advance of research on the molecular mechanisms of drug action and the cellular mechanisms of the emergence of resistance to cisplatin assists the rational design of new classes of platinum antitumor drugs, though details of both mechanisms still remain elusive. Information on DNA binding mode of platinum complexes, recognition and repair of DNA damage is instructive. Since several not cis isomers but trans isomers and not neutral complexes but cation complexes have been found active in vitro and in vivo, the early empirical structure-activity relationships of cisplatin analogues should be reevaluated. The hypothesis that platinum complexes which bind to DNA in a different manner will have different pharmacological properties has been tested, and now cationic multi-nuclear complexes and even trans-platinum complexes comprise unique classes of antitumor platinum-based agents with chemical and biological properties different from cisplatin. These new type platinum complexes are often effective to acquired cisplatin resistant tumor cells. In conclusion, the following complexes appear to offer great potential as new antitumor agents: (1) Complexes with distinctively different DNA interaction modes from cisplatin, which may circumvent intrinsic and acquired resistance to cisplatin through eluding the vigilance of DNA repair systems and (2) complexes with different tissue distribution or mechanisms of membrane transport which may exhibit a different spectrum of activity.     

The future challenges facing the development of new antimicrobial drugs

The emergence of resistance to antibacterial agents is a pressing concern for human health. New drugs to combat this problem are therefore in great demand, but as past experience indicates, the time for resistance to new drugs to develop is often short. Conventionally, antibacterial drugs have been developed on the basis of their ability to inhibit bacterial multiplication, and this remains at the core of most approaches to discover new antibacterial drugs. Here, we focus primarily on an alternative novel strategy for antibacterial drug development that could potentially alleviate the current situation of drug resistance--targeting non-multiplying latent bacteria, which prolong the duration of antimicrobial chemotherapy and so might increase the rate of development of resistance.     

The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension

Bioavailability (BA) and bioequivalence (BE) play a central role in pharmaceutical product development and BE studies are presently being conducted for New Drug Applications (NDAs) of new compounds, in supplementary NDAs for new medical indications and product line extensions, in Abbreviated New Drug Applications (ANDAs) of generic products and in applications for scale-up and post-approval changes. The Biopharmaceutics Classification System (BCS) has been developed to provide a scientific approach for classifying drug compounds based on solubility as related to dose and intestinal permeability in combination with the dissolution properties of the oral immediaterelease (IR) dosage form. The aim of the BCS is to provide a regulatory tool for replacing certain BE studies by accurate in-vitro dissolution tests. The aim of this review is to present the status of the BCS and discuss its future application in pharmaceutical product development. The future application of the BCS is most likely increasingly important when the present framework gains increased recognition, which will probably be the case if the BCS borders for certain class II and III drugs are extended. The future revision of the BCS guidelines by the regulatory agencies in communication with academic and industrial scientists is exciting and will hopefully result in an increased applicability in drug development. Finally, we emphasize the great use of the BCS as a simple tool in early drug development to determine the rate-limiting step in the oral absorption process, which has facilitated the information between different experts involved in the overall drug development process. This increased awareness of a proper biopharmaceutical characterization of new drugs may in the future result in drug molecules with a sufficiently high permeability, solubility and dissolution rate, and that will automatically increase the importance of the BCS as a regulatory tool over time.     

A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus

The development and progress of antidiabetic drugs (e.g., insulin preparations and hypoglycemic drugs) are retrospectively investigated in Japan. Their influences on the treatment of diabetes mellitus (DM) and its epidemiological aspects are also discussed. 1) Insulin preparations: Insulin was introduced for DM therapy in 1925, two or three years after its discovery in Canada. The preparations were raw extracts of bovine or porcine pancreas. These did not prevail widely in Japan because of the low incidence of DM before World Wan II. After the war, a shortage of mammalian materials compelled the use of fish pancreatic tissues such as bonito and/or tuna for insulin production. Insulin infection, so-called regular insulin, was first promoted in the 6th "Pharmacopoeia Japonica" (JP6) in 1951 and has been maintained to the present edition (JP14, 2001). Although depot-type insulin preparations were developed in the USA and Europe during the war, the introduction of those preparations to Japan was delayed until 1951, when Protamine zinc insulin appeared. Globin zinc insulin and Isophane insulin were introduced for clinical use in 1952 and 1955, respectively. These were also adopted for JP7 (1961). Biphasic-type insulin, which has a rapid onset and long duration of activity, appeared in 1965. Purified preparations from bovine or porcine sources have been available since 1980, which might be a strong reason for the decrease in insulin allergy. Insulin from animal origin has been supplied for almost 60 years since its discovery. Amino acid sequences of insulins from various species of animals were determined by the pioneering studies of Sanger and his associates. Human insulin, which differs from porcine insulin by only one amino acid, was produced by Novo researchers in 1982 using a semi-synthetic method. Then the Lilly group soon succeeded in obtaining human insulin by recombinant DNA technology in the same year. Both products were introduced to Japan in 1985, and the recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after-meal hyperglycemia of Type 2 diabetes. Epalrestat (Ono Yakuhin Co., 1992) is effective for diabetic neuropathy by reducing the formation of sorbitol. These anti-DM drugs were recently studied and developed in Japan. 4) The Japan Diabetes Society proposed a guideline on diagnostic criteria and treatment of diabetes mellitus (DM) in 1999 and revised it in 2002. DM is classified as insulin-dependent DM (Type l) and non-insulin dependent DM (Type 2). Type 1, juvenile onset DM, requires insulin therapy to prevent ketosis and to sustain life. Treatment of type 2, adult onset DM, is recommended as a step-by-step method, starting with dietary-exercise therapy, followed by oral hypoglycemic drugs and then insulin therapy. DM patients with complications should have a therapy devised to match their circumstances. 5) Epidemiological aspects: The mortality rate of DM compared to the time of drug appearance was traced from 1920 to 2000. The curve goes down slowly in the time frame of World War II, but rises from 1950 to 1970. The elevation could not be suppressed by the appearance of SUs, BGs or improved insulin preparations. The curve runs flat from 1980 to 1990, which might be related to the use of purified insulin or human insulin therapy. The mortality rate of DM indicates that death by hyperglycemic coma and other deaths resulting from complications are excluded. The survey of the principal cause of death by DM during the period of 1981-1990 indicates that the death rate due to hyperglycemic coma is only 1.7% of the total deaths caused by DM. The effect of drug therapy on all of the death resulting from DM is not detected. Hospital visitation and admission rates of the DM patients have been recorded since 1952 in Japan. This curve is rising continuously, and none of the antidiabetic drugs has been able to suppress it. These data show that the antidiabetic drugs relieve DM symptoms through their effective hypoglycemic actions, but that they cannot suppress the mortality rate of DM. It is possible that none of the drugs currently available can suppress the increasing tendency of DM patients.     

当代2型糖尿病临床治疗药物的研究进展

本文综述了国外抗糖尿病的研究进展,旨在对国内相同疾病药物利用提供借鉴与启发。目前已有多种有效的降糖药物。例如以肠促胰岛素为基础的治疗方式的进步包括一个微型可移植的渗透泵去持续的给予胰高血糖素样的肽段1受体,并且每周服用二肽基肽-4抑制剂的片剂。此外,钠-葡萄糖共运输抑制剂、脂肪连接蛋白受体竞争剂、选择性过氧化物酶体增殖物激活受体调节剂、细胞糖皮质激素抑制剂和纤维原细胞生长因子类似物都被广泛地认为是最具有潜力的降糖药物。能够提高胰岛素受体、后受体信号通路或者能够直接促进葡萄糖代谢选择通路的药物组分已经揭示了未来治愈糖尿病的可能性。