我国抗真菌药的研发进展及产销分析

目的:介绍咪唑类、三唑类、烯丙胺类、抗生素类等全身用抗真菌药的研发进展及市场应用趋势。方法:根据国内权威医药经济信息网站2002年~2004年有关抗真菌药市场和医院临床应用的数据,结合国内、外医药文献进行综述和分析。结果与结论:新剂型、真菌细胞壁抑制剂、三唑类抗真菌药的研发进展十分迅猛;临床应用排序前3位的分别为烯丙胺类、咪唑类和三唑类抗真菌药;抗真菌药销售额西安杨森制药有限公司名列榜首。     

吡咯类抗真菌药物的研究进展

目的:了解吡咯类抗真菌药物的研究进展。方法:收集、阅读、分析和归纳国内文献。结果:吡咯类,主要是三唑类抗真菌药比之于其他几类抗真菌药有更大的进展。结论:吡咯类抗真菌药虽有大的突破,但副作用仍大,且一旦治疗失效,使现有抗真菌药难于控制,是一难题,还需大力改进。     

南京地区33家医院2009-2011年抗真菌药利用分析

目的:了解南京地区医院抗真菌药的利用情况及趋势。方法:采用销售金额和用药频度(DDDs)分析及排序法,对南京地区33家医院2009-2011年抗真菌药的利用情况进行统计、分析。结果:该地区医院抗真菌药销售金额占抗菌药物总销售金额的比例呈逐年上升趋势。三唑类深部抗真菌药的销售金额构成比最大,年均增长率达14.66%,其中棘白霉素类药年均增长率最大(18.67%)。抗真菌药以进口品种为主,DDDs排序靠前的为三唑类药氟康唑和伊曲康唑,以及浅部抗真菌药特比萘芬。结论:该地区医院抗真菌药销售金额呈增长趋势,三唑类增长较为明显,提示临床应防范其耐药性的发生。     

2003年～2005年唑类抗真菌药市场分析

目的:分析2003年～2005年唑类抗真菌药的市场情况,以期对其研发生产及临床应用提供参考。方法:对《全国医药经济信息网》2003年～2005年唑类抗真菌药用药情况进行分析。结果及结论:唑类抗真菌药是临床上广泛应用的抗真菌药之一,其占抗真菌药的市场份额达到87.99%,我国唑类抗真菌药的使用虽呈现出不断增长的趋势,但我国自己的生产厂家,相对薄弱,发展空间已被新药和进口企业挤得很小。国产药厂要扭转这一局面,必须加强研制新药环节。     

2008—2010年南京地区抗真菌药应用分析

目的:分析2008—2010年南京地区抗真菌药使用现状及发展趋势。方法:采用金额和用药频度(DDDs)排序法,对南京地区31家入网医院的抗真菌药数据进行汇总并排序分析。结果:3年来,南京地区抗真菌药用药总金额逐年增加,三唑类代表药氟康唑、伊曲康唑和伏立康唑稳居用药金额排序前3位。抗真菌药市场以进口药为主。抗深部真菌药中三唑类的氟康唑和伊曲康唑,以及抗浅部真菌药中的特比萘芬和制霉菌素居DDDs排序前列。结论:2008—2010年南京地区抗真菌药用药金额呈增长趋势,临床疗效和是否为医保药品影响该类药物使用率。     

2008—2011年解放军总医院第一附属医院抗真菌药应用分析

目的:了解2008—2011年我院抗真菌药应用情况,为临床合理用药提供参考。方法:利用医院HIS系统软件,采用回顾性方法,对2008—2011年我院抗真菌药的销售金额、用药频度(DDDs)、限定日费用(DDC)及排序比等进行统计分析。结果:2008—2011年我院抗真菌药总销售金额和DDDs逐年显著增长,三唑类抗真菌药销售金额和DDDs每年均居首位,其中伊曲康唑是最常用的药品;4年中各药的DDC变化不大,DDC排序居前3位的药品分别为注射用伏立康唑(进口)、注射用卡泊芬净(进口)、注射用米卡芬净(进口)。结论:我院抗真菌药应用情况呈现明显的上升趋势,三唑类抗真菌药的使用频率最高。     

抗真菌药物的研究现状

真菌是一大类具有典型细胞核的真核细胞型微生物,近年来由于滥用抗生素引起菌群失调以及滥用激素,免疫抑制剂,抗癌药物和HIV染引起的免疫功能下降等原因,真菌病发病因素,尤其是条件致病性真菌引起的感染有明显上升趋势,正引起医学界的高度重视。因此,抗真菌药物的研发就显得格外迫切,抗真菌药物是指具有抑制杀死真菌生长或繁殖的药物。近些年抗真菌药的研究有了很大进展。不断有新型抗真菌药研发成功,高效、低毒的抗真菌药越来越成为研究的指导方向。     

149例呼吸科抗真菌药应用调查分析

目的:调查呼吸科患者抗真菌药的应用情况并初步评价用药的合理性。方法:采用回顾性调查方法,查阅患者的原始病历,根据合理用药指标,采用"限定日剂量"、"用药频度"、"药物利用指数"等分析评价用药情况。结果:使用抗真菌药的149例患者中,老年、使用广谱抗菌药物、合并糖尿病或进行呼吸道侵入操作的患者较多地使用了抗真菌药;白色念珠菌感染46例(92%);预防性用药103例(68%);使用的抗真菌药均为唑类抗真菌药的2个品种。氟康唑和伊曲康唑是常用的抗真菌药品种,DUI值分别为1.43和1.5;抗真菌药使用前后6例出现一过性的肝损害,1例肾损害。结论:呼吸科抗真菌药应用基本合理,但存在用药剂量偏大的情况,需进一步规范抗真菌药的应用,提高用药的安全性与合理性。     

三氮唑类抗真菌药物的研究进展

临床上主要用于治疗真菌感染的药物可分为四类：多烯抗生素类、氮唑类、烯丙胺、硫代氨基甲酸盐类以及氯代喀陡类（见表）。近年来，随着伊曲康唑和氟康唑在治疗曲霉菌、全身性念珠菌以及脑膜炎隐球菌感染上取得的较好疗效，氮唑类特别是三氮唑类抗真菌药以其高效。广谱的抗菌活性和对大多数酵母菌及丝状菌的抑制作用引起了科学家们的日益重视[1，2]。国外学者对三氮唑类抗真菌药物进行了大量的研究，现将有关进展综述如下。来临床应用的抗真菌药的作用机制1作用机制三氯峻类抗真菌药物主要是抑制真菌细胞内麦角带醇的生物合成。麦角自醇为…     

武汉地区32家医院2009～2011年外用抗真菌药应用分析

目的:研究外用抗真菌药物在武汉地区的应用情况和发展趋势,为药品生产、经营、使用等部门提供参考。方法:对武汉地区32家医院2009～2011年外用抗真菌药的使用数量、金额进行统计分析。结果:2009～2011年,外用抗真菌药总体销售金额和药品种数逐年上升。3年来唑类抗真菌药销售金额均列第1位;软膏剂的使用金额均列第1位;曲安奈德益康唑销售金额均列第1位。结论:武汉地区医院抗真菌药使用量及销售金额在逐年上升,品种、剂型也不断增加,应提倡合理使用。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.