他汀类药物治疗动脉粥样硬化的作用机制

他汀类药物是一种降胆固醇药物,随着临床的广泛应用,它的降脂效果已经得到了肯定。此外,他汀类药物对动脉粥样硬化为主的心血管疾病的治疗还包括改善血管内皮功能、抑制血管平滑肌细胞增生和迁移、维持粥样斑块的稳定性,以及抑制泡沫细胞的形成。它的这种多效性使其在心血管疾病治疗中处于越来越重要的地位。     

非诺贝特微球对高血脂模型大鼠降脂作用研究

研究非诺贝特对高血脂症模型大鼠降脂作用。高效液相色谱法检测非诺贝特缓释微球载药量,进行体外释放及动物体内药效学研究等,经验证在体内具有缓释降脂作用。制备所得非诺贝特微球粒径大小均一。药物的体外释放和稳定性均符合要求,对高血脂症具有显著降脂疗效,体内高血脂动物模型的降脂试验得到良好的预期效果,为非诺贝特新剂型开发提供了良好的理论依据。     

他汀类药物的晶型研究进展

综述了近年来几种常用他汀类药物的晶型研究进展,介绍了不同晶型和非晶型他汀类药物。认为非晶型他汀类药物创造了提高该类药物溶解度和生物利用度的可能性,同时也增加了其治疗心血管疾病有效性的机会,为原料药的生产工艺优化及制剂对原料药晶型选择提供参考,且更多具有优势的晶型（如更好的溶解性、稳定性等）可能被发现。     

三类畅销药谨慎投入

胆固醇调节类药物是否言过其实 近年最为畅销的胆固醇调节类药物为他汀类药物。在美国，他汀类药物处方量惊人．     

前蛋白转化酶枯草溶菌素9抑制剂的研发进展及应用

血脂异常是动脉粥样硬化性心血管疾病（atherosclerotic cardiovascular disease,ASCVD）最主要的致病因素，降脂治疗是预防和管理ASCVD的主要方式之一。前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)可通过升高低密度脂蛋白胆固醇（low-density lipoprotein cholesterol,LDL-C）、炎性反应等促进动脉粥样硬化，而PCSK9抑制剂可靶向降低PCSK9水平，降脂效率高。联合他汀类或依折麦布治疗的基础上，还能带来更多的临床效益，随着研究的不断深入，已成为近年降脂药研究的热点。本文就PCSK9抑制剂的研发进展作一综述，以期为该类药物的临床应用提供参考。     

匹伐他汀钙的合成方法研究进展

匹伐他汀是第三代他汀类药物。该药不仅具有较强的3-羟基-3-甲基戊二酰辅酶A还原酶抑制作用,而且呈肝细胞选择性,已被制药界誉为是＂超级他汀＂。本文通过7条合成路线,分别从拆分法和不对称合成法介绍了降血脂药匹伐他汀钙的合成,并详细分析了这些路线的优缺点。得出结论：不对称合成法优于拆分法,手性（3R,5S）立体构型是合成的难点和重点。     

辛伐他汀的合成工艺

他汀类药物系现在国际上热点普及的调血脂药物，属于羟甲戊二酰辅酶A(HMGCoA)还原酶抑制剂类，能选择性地降低低密度酯蛋白，降低甘油三酯，升高高密度酯蛋白，对防治动脉粥样硬化、冠心病等有重要意义。他汀类药物的代表有罗伐他汀、普伐他汀及全合成氟伐他汀等，通过抑制HMGCOA还原酶，而降低体内的内源性胆固醇水平，选择性高，疗效确切，对原发性高胆固醇及异常高血脂症都有显著疗效，可大大降低冠心病的发病率和死亡率。这类药物的开发成功，是降血脂药物研究的一个突破性进展。     

他汀类药物研究获新证据

日前在奥地利维也纳召开的2007年欧洲心脏病学（ESC）年会上公布了两项他汀类药物的最新研究结果：一项最新随机前瞻性研究的结果显示，他汀类药物除了有降胆固醇的作用以外，还可以降低慢性心力衰竭患者心源性猝死的发生率；另一项在英国初级保健数据库中进行的大规模观察性研究表明，原来服用阿托伐他汀钙片的患者在换用辛伐他汀后，与一直接受阿托伐他汀钙治疗的患者相比，发生主要心血管事件，包括心肌梗死、卒中、某些类型心脏手术、死亡的相对风险增加30％，相关研究报告已发表于《英国心脏病学杂志》上。[第一段]     

喹诺酮类药物的研究进展

喹诺酮类药物是一类人工合成的抗菌药物,目前广泛应用于临床抗感染治疗中,具有较强的抗菌活性。本文主要从喹诺酮类药物的作用机制、临床应用、不良反应及耐药机制等方面进行分析和整理,综述其研究进展并对其未来的研究方向提出了建议,希望为今后喹诺酮药物的研究提供一定的参考依据。     

调血脂原料药市场概况

据不完全统计，全球开发的他汀类药物已有12个品种。在我国市场上已有8个品种，分别是阿托伐他汀、辛伐他汀、普伐他汀、氟伐他汀、洛伐他汀、美伐他汀、瑞舒伐他汀、匹伐他汀。近年来，全球调血脂药及他汀类药品市场迅猛发展，2004年“IMS药品零售监测数据系统”显示，全球调血脂药销售总额已达262．4亿美元，比上一年增长了12．2％逐渐回升。     

Pleiotropic Effects of PCSK-9 Inhibitors

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications.     

Clinical neuroprotective drugs for treatment and prevention of stroke

Stroke is an enormous public health problem with an imperative need for more effective therapies. In therapies for ischemic stroke, tissue plasminogen activators, antiplatelet agents and anticoagulants are used mainly for their antithrombotic effects. However, free radical scavengers, minocycline and growth factors have shown neuroprotective effects in the treatment of stroke, while antihypertensive drugs, lipid-lowering drugs and hypoglycemic drugs have shown beneficial effects for the prevention of stroke. In the present review, we evaluate the treatment and prevention of stroke in light of clinical studies and discuss new anti-stroke effects other than the main effects of drugs, focusing on optimal pharmacotherapy.     

Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia

Cardiovascular disease (CVD) is the leading cause of death worldwide and is the clinical manifestation of the atherosclerosis. Elevated LDL-cholesterol levels are the first line of therapy but the increasing prevalence in type 2 diabetes mellitus (T2DM) has positioned the cardiometabolic risk as the most relevant parameter for treatment. Therefore, the control of this risk, characterized by dyslipidemia, hypertension, obesity, and insulin resistance, has become a major goal in many experimental and clinical studies in the context of CVD. In the present review, we summarized experimental studies and clinical trials of recent anti-diabetic and lipid-lowering therapies targeted to reduce CVD. Specifically, incretin-based therapies, sodium-glucose co-transporter 2 inhibitors, and proprotein convertase subtilisin kexin 9 inactivating therapies are described. Moreover, the novel molecular mechanisms explaining the CVD protection of the drugs reviewed here indicate major effects on vascular cells, inflammatory cells, and cardiomyocytes, beyond their expected anti-diabetic and lipid-lowering control. The revealed key mechanism is a prevention of acute cardiovascular events by restraining atherosclerosis at early stages, with decreased leukocyte adhesion, recruitment, and foam cell formation, and increased plaque stability and diminished necrotic core in advanced plaques. These emergent cardiometabolic therapies have a promising future to reduce CVD burden.     

Zebrafish as a Model for the Study of Lipid-Lowering Drug-Induced Myopathies

Drug-induced myopathies are classified as acquired myopathies caused by exogenous factors. These pathological conditions develop in patients without muscle disease and are triggered by a variety of medicaments, including lipid-lowering drugs (LLDs) such as statins, fibrates, and ezetimibe. Here we summarise the current knowledge gained via studies conducted using various models, such as cell lines and mammalian models, and compare them with the results obtained in zebrafish (Danio rerio) studies. Zebrafish have proven to be an excellent research tool for studying dyslipidaemias as a model of these pathological conditions. This system enables in-vivo characterization of drug and gene candidates to further the understanding of disease aetiology and develop new therapeutic strategies. Our review also considers important environmental issues arising from the indiscriminate use of LLDs worldwide. The widespread use and importance of drugs such as statins and fibrates justify the need for the meticulous study of their mechanism of action and the side effects they cause.     

强化降脂与介入治疗在冠心病二级预防中的效果比较

目的 探讨比较强化降脂与介入治疗治疗在冠心病二级预防中的效果。方法 选取2009年1月至2010年1月于我院进行治疗的120例冠心病患者为研究对象,将其随机分为A组(强化降脂组)60例和B组(介入治疗组)60例,后将2组患者的心肌梗死发生率、心绞痛发生率、再次住院率及治疗前及治疗后1个月及3个月的血脂、血清hs-CRP、UA水平进行检测及比较。结果 经研究比较发现,A组的心肌梗死发生率、心绞痛发生率、再次住院率均低于B组,A组治疗后1个月及3个月的血清TG、TC及LDL-C、hs-CRP、UA水平均明显低于B组,而血清HDL-C的水平则高于B组,P均<0.05,均有显著性差异。结论 强化降脂治疗在冠心病二级预防中的效果较好,值得临床推广及应用。     

Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation

Statins represent the most prescribed class of drugs for the treatment of hypercholesterolemia. Effects that go beyond lipid-lowering actions have been suggested to contribute to their beneficial pharmacological properties. Whether and how statins act on macrophages has been a matter of debate. In the present study, we aimed at characterizing the impact of statins on macrophage polarization and comparing these to the effects of bempedoic acid, a recently registered drug for the treatment of hypercholesterolemia, which has been suggested to have a similar beneficial profile but fewer side effects. Treatment of primary murine macrophages with two different statins, i.e., simvastatin and cerivastatin, impaired phagocytotic activity and, concurrently, enhanced pro-inflammatory responses upon short-term lipopolysaccharide challenge, as characterized by an induction of tumor necrosis factor (TNF), interleukin (IL) 1β, and IL6. In contrast, no differences were observed under long-term inflammatory (M1) or anti-inflammatory (M2) conditions, and neither inducible NO synthase (iNOS) expression nor nitric oxide production was altered. Statin treatment led to extracellular-signal regulated kinase (ERK) activation, and the pro-inflammatory statin effects were abolished by ERK inhibition. Bempedoic acid only had a negligible impact on macrophage responses when compared with statins. Taken together, our data point toward an immunomodulatory effect of statins on macrophage polarization, which is absent upon bempedoic acid treatment.     

Effect of Ecdysterone on the Hepatic Transcriptome and Lipid Metabolism in Lean and Obese Zucker Rats

Conflicting reports exist with regard to the effect of ecdysterone, the predominating representative of steroid hormones in insects and plants, on hepatic and plasma lipid concentrations in different rodent models of obesity, fatty liver, and diabetes, indicating that the effect is dependent on the rodent model used. Here, the hypothesis was tested for the first time that ecdysterone causes lipid-lowering effects in genetically obese Zucker rats. To test this hypothesis, two groups of male obese Zucker rats (n = 8) were fed a nutrient-adequate diet supplemented without or with 0.5 g ecdysterone per kg diet. To study further if ecdysterone is capable of alleviating the strong lipid-synthetic activity in the liver of obese Zucker rats, the study included also two groups of male lean Zucker rats (n = 8) which also received either the ecdysterone-supplemented or the non-supplemented diet. While hepatic and plasma concentrations of triglycerides and cholesterol were markedly higher in the obese compared to the lean rats (p < 0.05), hepatic and plasma triglyceride and cholesterol concentrations did not differ between rats of the same genotype fed the diets without or with ecdysterone. In conclusion, the present study clearly shows that ecdysterone supplementation does not exhibit lipid-lowering actions in the liver and plasma of lean and obese Zucker rats.     

Powdered activated carbon‐assisted biotreatment of a chemical synthesis wastewater

The effect of powdered activated carbon (PAC) on the biotreatment of an industrial wastewater taken from a chemical plant synthesising drugs for the pharmaceutical sector was studied. Industrial and domestic wastewaters were combined at laboratory scale and the effect of PAC addition was tested in aerobic reactors. The aim of this addition was to decrease inhibitory and non‐biodegradable organics. Two different procedures were applied in testing the effectiveness of PAC. First, PAC was directly added to activated sludge mixed liquor. In the second case, industrial wastewater was first contacted with PAC and then treated biologically. In the evaluation of performance, COD measurements, oxygen uptake rate (OUR) measurements and measurements in the ultraviolet‐visible (UV‐Vis) spectra were taken into consideration. Both direct PAC addition and PAC pretreatment led finally to similar results. In both cases, the concentration of non‐biodegradable matter could be lowered. In particular, the colour of the wastewater was significantly reduced. Direct PAC addition appeared to be more practical and plausible. In any case, PAC addition to activated sludge increased the OUR of the sludge, indicating that inhibition could be decreased. The study also pointed out that in the assessment of PAC performance, the combined evaluation of OUR, spectral parameters and COD would be much more informative than the COD parameter alone. © 2001 Society of Chemical Industry     

Comparison of the Effects of Statins on A549 Nonsmall-Cell Lung Cancer Cell Line Lipids Using Fourier Transform Infrared Spectroscopy: Rosuvastatin Stands Out

Statins are commonly prescribed antilipidemic and anticholesterol class of drugs. In addition to their major role, they have been found to have anticancer effects on in vitro, animal and clinical studies. The aim of this study was to investigate the effects of six different statins (rosuvastatin, pravastatin, simvastatin, lovastatin, fluvastatin, and atorvastatin) on A549 cancer cells lipids by Fourier transform infrared (FTIR) spectroscopy. Proliferation tests were carried out to detect the half-maximal inhibitory concentrations (IC₅₀) of each statin on A549 cells. The IC₅₀ values were 50 μM for simvastatin, 150 μM for atorvastatin and pravastatin, and 170 μM for fluvastatin, 200 μM for rosuvastatin and lovastatin on A549 cells. No correlation was found between the antiproliferative effects of the statins and lipid-lowering effect. The cells were treated with IC₅, IC₁₀, and IC₅₀ values of each statins concentration and lipid extracts were compared using FTIR spectroscopy. The results indicated that different statins had different effects on the lipid content of A549 cells. The FTIR spectra of the lipid exctracts of statin-treated A549 cells indicated that the value of hydrocarbon chain length, unsaturation index, oxidative stress level, and phospholipid containing lipids increased except for rosuvastatin-treated A549 cells. In addition, rosuvastatin significantly lowered cholesterol ester levels. In conclusion, the contrasting effects of rosuvastatin should be further investigated.     

Incorporation of chloramphenicol and captopril into poly(GL)‐b‐poly(GL‐co‐TMC‐co‐CL)‐b‐poly(GL) monofilar surgical sutures

Incorporation of chloramphenicol and captopril into coated and uncoated monofilament sutures was evaluated, as well as the derived bactericide and wound healing effects. To this end, a commercially available suture and an amorphous random copolymer constituted by trimethylene carbonate and lactide units were considered. The suture had a segmented architecture based on polyglycolide hard blocks and a soft block constituted by glycolide, trimethylene carbonate and ε‐caprolactone units. Chloramphenicol was better loaded when the coating copolymer was employed due to its protective effect whereas captopril showed an opposite behavior due to partial solubilization during immersion in the coating bath. Interestingly, the release behavior was very different for the two studied drugs since a significant retention of chloramphenicol was always detected, suggesting the establishment of interactions between drug and copolymers. On the other hand, delivery of captopril showed a typical dose dependent behavior. A low in vitro toxicity of the two drugs was determined considering both epithelial‐like and fibroblast‐like cells. Bactericide effect of chloramphenicol against Gram‐negative and Gram‐positive bacteria was demonstrated at a dose that was non‐toxic for all assayed cells. An accelerating wound healing effect of captopril was also demonstrated for early events. In this case, the use of a coating copolymer was fundamental to avoid cytotoxic effects on highly loaded sutures. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44762.