莽草酸及其代谢产物在医药工业中的应用

莽草酸代谢途径是芳香族氨基酸合成过程中的一段共同代谢途径,广泛存在于植物和微生物中。莽草酸途径的代谢产物莽草酸、奎尼酸和没食子酸均含有多功能的六碳环状结构以及3个不对称的碳原子手性中心,可以在化学修饰下形成一系列具有潜在药理学活性的衍生物,广泛应用于医药工业。文章着重介绍莽草酸代谢途径的相关产物及其衍生物在抗病毒、抗肿瘤、抗菌、抗炎及抗血栓等方面的应用。     

LC-MSn比较分析三种传统中草药中绿原酸及其衍生物组分

利用LC-MSⁿ分析了杜仲叶、金银花叶以及鱼腥草叶甲醇提取物中绿原酸及其异构体和衍生物。发现3种样品中都含有3种单咖啡酰奎尼酸(绿原酸)， 分别是3-咖啡酰奎尼酸(3-caffeoylquinic acid，3-CQA)、 4-CQA和5-CQA。杜仲叶和金银花叶中5-CQA为主要成分，但鱼腥草叶中以3-CQA和4-CQA为主要成分。在杜仲叶中首次发现咖啡酰奎尼酸糖苷；另外还发现金银花叶中有少量5-阿魏酰奎尼酸(5-feruloylquinic acid，5-FQA)；鱼腥草叶含有少量的3-FQA和4-肉桂酰奎尼酸(4-p-coumaroylquinic acid，4-pCoQA)。本文首次报道鱼腥草叶中绿原酸异构体成分，为3-CQA和4-CQA的开发提供了来源(植物中绿原酸的结构一般以5-CQA为主)。     

大黄素及其衍生物：合成与药理作用研究进展

大黄酸是大黄的主要成分之一,其应用广泛,可用于抗肿瘤、抗病毒、糖尿病肾病、抑菌、抗炎等,具有不错的临床应用价值。本文主要综述近年大黄酸及其衍生物的合成与药理活性方面的研究进展,以期为大黄酸及其衍生物的开发应用提供参考依据。     

从“达菲”抗禽流感论医药技术创新价值

达菲作为预防及治疗禽流感的药物,2009年销售额达到30亿美元的高峰。罗氏公司的科学家以莽草酸代替奎尼酸,改善了达菲最初的生产过程,解决了大规模生产的原料供应问题,而莽草酸原料主要从原产于中国的八角中提取。由于有严密的专利保护,罗氏公司可独享这块市场。由此说明技术创新对医药企业发展的重要性,提示中国经济取得重大发展后,应大力开展医药领域的创新,壮大自己的民族医药企业。     

脱咖啡因绿茶提取物中活性成分3-邻没食子酰奎尼酸和L-茶氨酸对大鼠离体海马电生理学的影 响

绿茶中主要的刺激性成分为咖啡因,此外还含特有成分3一邻没食子酰奎尼酸、L-茶氨酸以及其他一些化合物。脱咖啡因绿茶富含3-邻没食子酰奎尼酸和 L-茶氨酸,而缺乏其他成分;前2个成分对脑直接给药是否具药理活性尚不清楚。为此研究了富含3-邻没食子酰奎尼酸和 L-茶氨酸的脱咖啡因绿茶提取物及其他成分对离体大鼠海马组织电生理学的     

水溶性五环三萜酸衍生物的制备及研究进展

综述几种常见水溶性五环三萜酸衍生物的研究进展。五环三萜酸类化合物多具有广泛的生物活性,但因水溶性差、生物利用度低使其临床应用受到限制。以五环三萜酸为先导化合物,经结构修饰合成水溶性衍生物,并从中寻找出有生物活性和临床应用价值的化合物是当前天然药物化学研究的热点之一。     

叶绿素衍生物在医药上的应用

在过去的一个半世纪内,叶绿素及其在植物生命中的作用曾经是广泛研究的课题,但它在医药上的应用则始于二十年代。自用叶绿素及其衍生物治疗动物实验性贫血取得满意的结果后,不久又发现叶绿素衍生物除能促进造血功能,对贫血有治疗价值外,还具     

不同产地加工方法对野菊花中二咖啡酰奎尼酸类成分含量的影响

目的：建立测定野菊花中二咖啡酰奎尼酸类成分含量的方法,并比较不同产地加工方法对其含量的影响,为确定其较佳加工方法提供依据。方法：采用高效液相色谱法。色谱柱为DiamonsilC18（250mm×4．6mm,5μm）,流动相为0．1％磷酸溶液。甲醇（梯度洗脱）,检测波长为326nm,柱温为25℃,流速为0．8ml／min。结果：3,4-二咖啡酰奎尼酸、3,5．二咖啡酰奎尼酸和4,5-二咖啡酰奎尼酸的进样量分别在87．36~873．60、65．81~658．10、32．00~320．00ng范围内与各自峰面积积分值呈良好的线性关系（,分别为0．9999、0．9999、0．9998）;精密度、稳定性、重复性试验的RSD〈2％;平均加样回收率分别为99．59％、99．65％、99．50％,RSD分别为1．53％、1．78％、2．27％（n均为6）。结论：该方法操作简便、结果准确、重复性好,可用于野菊花中二咖啡酰奎尼酸类成分的含量测定。野菊花中二咖啡酰奎尼酸类成分的含量除与温度有关外,还与烘晒时间长短有一定的关系。     

二咖啡酰奎尼酸片健康人体安全性及耐受性研究

目的:评价健康志愿者单剂量及多剂量口服二咖啡酰奎尼酸片的安全性和耐受性。方法:按照GCP要求设计试验方案。单剂量给药58名受试者随机分至7个剂量组,每组4~10名,多剂量给药30名受试者随机分至3个剂量组,男女各半,从低剂量开始给药,单剂量给药结束后进行多剂量给药,多剂量给药10 d,观察指标为临床症状、生命体征和实验室检查指标等,采用描述性分析及SAS软件进行统计学处理。结果:在单剂量及多剂量给予二咖啡酰奎尼酸片耐受性试验中,各组受试者入选时各项指标均在正常范围,条件均衡,具有可比性。共报告9件被研究者判定为可能与研究药物有关的不良事件,且未经处理均消失。不良事件主要表现为窦性心动过缓、血白细胞降低,无自觉症状,均完成临床试验,其他均未见有临床意义的改变。结论:88名健康受试者中单剂量口服二咖啡酰奎尼酸片,最大剂量至1 200 mg;多剂量口服二咖啡酰奎尼酸片,最大剂量至500 mg,每12 h 1次,均安全且能很好耐受。     

不同产地野菊花中绿原酸、4, 5-二咖啡酰奎尼酸的含量测定

目的建立不同产地野菊花中绿原酸、4,5-二咖啡酰奎尼酸的含量测定方法。方法采用HPLC,色谱柱为DiamonsilC18(4.6 mm×250 mm,5μm);采用梯度洗脱;检测波长327 nm;柱温30℃;流速1.0 mL.min 1。结果绿原酸、4,5-二咖啡酰奎尼酸的线性范围分别为0.011～0.22μg,0.017 5～0.35μg。加样回收率分别为99.1%和98.8%;RSD分别为1.93%和1.54%(n=9)。结论本方法操作简便,分析速度快,结果准确,重复性好,可用于野菊花中绿原酸和4,5-二咖啡酰奎尼酸含量的测定。     

5-取代苯基-3-吡唑烷酮衍生物的合成及抗癫痫作用研究

目的寻找具有抗癫痫作用的化合物.方法以取代苯甲醛为起始原料经缩合、酯化、环合及酰化得目标化合物,对所得化合物采用最大电惊厥法测定其抗癫痫活性.结果合成了7个未见文献报道的5-取代苯基-3-吡唑烷酮衍生物.结论初步药理实验表明,化合物4c、4e显示出较强的抗癫痫活性.     

阿司匹林衍生物药理活性研究概述

阿司匹林具有多种药理活性,是老药新用的典型药物之一。近年来,人们为开发阿司匹林,对其结构进行修饰及改造,以期得到副作用更小、活性更好的衍生物。本文总结了30种阿司匹林衍生物的合成路线及药理活性。其药理活性主要集中在解热镇痛、抗炎、抗骨质疏松、防治心脑血管疾病及抗肿瘤活性等方面,可为相关研究和应用提供参考。     

熊果酸纳米制剂的研究进展

熊果酸是一种具有保肝、抗炎、抗癌等多种生物活性的五环三萜类化合物,药理活性广泛。但是,较低的水溶性和生物利用度等缺陷限制了其临床应用。因此,开发新剂型以提高熊果酸的生物利用度成为熊果酸研究的重要部分。纳米载体广泛应用于改善药物水溶性,提高药效、延长药物作用时间。本文总结了国内外熊果酸纳米制剂的相关研究,包括脂质体、胶束、纳米粒、纳米悬浮液和纳米乳,为其后续研究提供必要的思路和参考。     

Biochemical and pharmacological characterization of isatin and its derivatives: from structure to activity

Isatin, 1H-indole-2,3-dione, is a heterocyclic compound of significant importance in medicinal chemistry. It is a synthetically versatile molecule, a precursor for a large number of pharmacologically active compounds. Isatin and its derivatives have aroused great attention in recent years due to their wide variety of biological activities, relevant to application as insecticides and fungicides and in a broad range of drug therapies, including anticancer drugs, antibiotics and antidepressants. The purpose of this review is to provide an overview of the pharmacological activities of isatin and its synthetic and natural derivatives. Molecular modifications to tailor the properties of isatin and its derivatives are also discussed.     

Pharmacological properties of the ubiquitous natural product betulin.

Betulin (lup-20(29)-ene-3beta,28-diol) is an abundant naturally occurring triterpene and it is found predominantly in bushes and trees forming the principal extractive (up to 30% of dry weight) of the bark of birch trees. Presently, there is no significant use for this easily isolable compound, which makes it a potentially important raw material for polymers and a precursor of biologically active compounds. Betulin can be easily converted to betulinic acid, which possesses a wide spectrum of biological and pharmacological activities. Betulinic acid has antimalarial and anti-inflammatory activities. Betulinic acid and its derivatives have especially shown anti-HIV activity and cytotoxicity against a variety of tumor cell lines comparable to some clinically used drugs. A new mechanism of action has been confirmed for some of the most promising anti-HIV derivatives, which makes them potentially useful additives to the current anti-HIV therapy. Betulinic acid is specifically cytotoxic to several tumor cell lines by inducing apoptosis in cells. Moreover, it is non-toxic up to 500 mg/kg body weight in mice. The literature concerning derivatization of betulin for structure-activity relationship (SAR) studies and its pharmacological properties is reviewed.     

芦丁药理作用与新剂型的研究进展

芦丁是一种天然的黄酮类化合物,在临床上常被用于治疗心血管类疾病,具有抗心肌损伤、抗炎、抗氧化、抗细胞凋亡、抗菌、抗病毒等药理活性,不良反应小。芦丁是治疗多种疾病的潜力药物,但因水溶性差和渗透性差导致口服生物利用度低,而在临床应用中受限。为了提高芦丁的水溶性和渗透性,改善生物利用度,多种新型芦丁制剂被研究。本文查阅国内外相关文献和报道,对芦丁的基本性质、药理作用、生物利用度和药动学研究现状进行归纳,并总结了芦丁的新剂型研究,阐述不同剂型对芦丁生物利用度和药动学参数的影响,为研发芦丁相关新药提供参考。     

海绵的生物活性研究新进展

海洋物种是生物多样性的来源,能够产生结构多样、生物活性多样的次生代谢物。海绵是其中最丰富的天然产物来源,其药理活性丰富,具有极高的临床应用价值,被认为是药物宝库。目前人们已经发现其具有抗肿瘤、抗病毒、抗菌、抗氧化、抗炎、免疫调节等生物活性。多年来,对海绵的化学成分研究较多,但对其丰富的生物活性研究相对较少。对海绵次生代谢物的生物活性研究现状进行综述,以期发现活性较好的化合物,为新药开发提供依据。此外,还从药物开发领域对进入临床实验的海绵衍生化合物成药性、成本效益等进行讨论。     

Pharmacokinetics-pharmacology disconnection of herbal medicines and its potential solutions with cellular pharmacokinetic-pharmacodynamic strategy

Recently, there is a global trend of using herbal medicines to treat various chronic diseases and promote health. But the controversy over the safety and efficacy of herbal medicines is a focus of attention, primarily because of the many unknown and unrevealed natures of herbal medicines, which strongly restricts their application and development. Pharmacokinetics is a bridge linking the herbal medicines and their pharmacological responses. It is assumed in traditional pharmacokinetics that an excellent drug should have appropriate pharmacokinetic behaviours and its pharmacological effect is related with plasma drug concentrations. However, most herbal medicines exhibit excellent pharmacological responses despite poor pharmacokinetic behaviours. As most drugs are intracellulartargeted, we put forward cellular pharmacokinetic-pharmacodynamic strategy, which is focused on the intracellular fate of drugs. This strategy could partially explain the marked pharmacological activities of herbal medicines from their intracellular pharmacokinetic behaviours, rather than their plasma concentrations. It is a helpful complementarity to traditional pharmacokinetics, and takes a potential role in the research and development of new herb-origined drugs. In this review, the pharmacokinetics-pharmacology disconnections of herbal medicines (such as ginseng, berberine and danshen) are retrospected. Then our proposed cellular pharmacokineticpharmacodynamic strategy, its characteristics, as well as its research procedures are described, followed by the subcellular distributions of drug transporters and metabolic enzymes which are the determinants of cellular pharmacokinetics-pharmacodynamics. Finally, our successful applications of cellular pharmacokinetic-pharmacodynamic strategy in elucidating ginsenoside Rh2 as an adjuvant agent and tanshinone IIA as an anticancer agent are illustrated.     

The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target

Relatively high doses of nicotinic acid induce a profound change in the lipid and lipoprotein profile. In particular, the ability of nicotinic acid to decrease low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol levels has led to its use as an antidyslipidemic drug. The mechanisms underlying the pharmacological effects of nicotinic acid have been unclear for decades. The recent discovery of a nicotinic acid receptor that is a G-protein-coupled receptor has led to a renewed interest in the pharmacological effects of nicotinic acid. This review summarizes recent progress in understanding the physiological and pharmacological role of the nicotinic acid receptor and discusses its potential use as a new target for the development of antidyslipidemic drugs to prevent and treat cardiovascular diseases.     

Pharmacology of benzydamine

Benzydamine is a topical anti-inflammatory drug which is widely available and used topically for the treatment of the mouth. It is also used as a gel for application to inflamed joints. It has physicochemical properties and pharmacological activities which differ markedly from those of the aspirin-line non-steroidal anti-inflammatory drugs. Benzydamine is a weak base unlike the aspirin-like drugs which are acids or metabolized to acids. A major contrast with the aspirin-like drugs is that benzydamine is a weak inhibitor of the synthesis of prostaglandins but it has several properties which may contribute to its anti-inflammatory activity. These properties include inhibition of the synthesis of the inflammatory cytokine, tumour necrosis factor-α (EC₅₀, 25 μmol/L). Inhibition of the oxidative burst of neutrophils occurs under some conditions at concentrations of 30 to 100 μmol/L, concentrations which may be produced within oral tissues after local application. A further activity of benzydamine is a general activity known as membrane stabilization which is demonstrated by several actions including inhibition of granule release from neutrophils at concentrations ranging from 3 to 30 μmol/L and stabilization of lysosomes. Lack of knowledge of the tissue concentrations of benzydamine limit the correlation between pharmacological activities in vitro and in vivo. The concentration of benzydamine in the mouthwash is 4 mmol/L but the concentrations in oral tissues have not been studied adequately. Limited data in the rat indicates that concentrations of benzydamine in oral tissues are approximately 100 μmol/L.