甲氨喋呤及来氟米特联合补肾壮骨止痛汤治疗类风湿关节炎的临床研究

目的 观察甲氨蝶呤(MTX)、来氟米特(LEF)联合补肾壮骨止痛汤治疗类风湿关节炎的疗效.方法 通过观察治疗类风湿关节炎的主要指标疗效和疾病疗效,对比分析补肾壮骨止痛汤联合甲氨喋呤、来氟米特与甲氨喋呤联合来氟米特治疗类风湿关节炎的疗效和安全性.结果 40例类风湿关节炎患者完成为期15w的研究,补肾壮骨止痛汤联合甲氨喋呤、来氟米特组(以下称治疗组)及甲氨喋呤联合来氟米特组(以下称对照组)各20例.主要指标疗效以及疾病疗效在疗程后期有显著性差异(P<0.05),治疗组优于对照组.结论 甲氨喋呤、来氟米特联合补肾壮骨止痛汤治疗类风湿关节炎可起到增效减毒的作用,是一个安全且有效的治疗方案.     

来氟米特联合甲氨蝶呤治疗类风湿关节炎的疗效评价

目的：评价来氟米特联合甲氨蝶呤对类风湿关节炎的治疗效果和安全性。方法：选取2014年3月～2015年12月于我院风湿免疫科就诊的类风湿关节炎患者100例,随机均分为联合组和单纯组,联合组接受来氟米特合甲氨蝶呤治疗,单纯组只接受甲氨蝶呤单独治疗;治疗结束后比较两组临床症状改善情况,血沉、炎症相关因子改变指标等,并分析联合用药的安全性。结果：联合组临床症状和血清学指标改善情况均较单纯组明显（P＜0.05）,药物副反应两组无明显差异（P﹥0.05）。结论：联合运用来氟米特和甲氨蝶呤治疗类风湿关节炎疗效确切安全性高,临床应用时结合患者的疾病状况使用。     

来氟米特与甲氨蝶呤治疗类风湿关节炎的开放对照研究

目的：对比来氟米特和甲氨蝶呤治疗类风湿性关节炎患者的临床疗效和安全性。方法：随机选择活动期类风湿性关节炎患者96例,分为LEF组48例,给予来氟米特20mg,口服,每天1次;MIX组48例,给予甲氨蝶呤10mg,口服,每周1次,4—6周后停用。观察两组治疗后症状、体征、不良反应改善情况。结果：两种药物治疗类风湿性关节炎的疗效均在90．0％以上,同时大多数患者耐受性好,不良反应轻,两组相比较,差异无统计学意义。结论：来氟米特与甲氨蝶呤治疗类风湿关节炎疗效都比较好,副作用少,花费较低,是类风湿关节炎的可取治疗方案。     

来氟米特单独及联合甲氨蝶呤对类风湿关节炎患者体征改善及血清CRP、ESR水平变化的影响

目的:探究在类风湿关节炎治疗的过程中,使用来氟米特单独治疗及联合甲氨蝶呤治疗的效果。方法:针对40例类风湿关节炎患者采用来氟米特单独治疗,并归为对照组,针对另外40例患者在对照组基础上联合使用甲氨蝶呤治疗,并归为观察组,两组患者均为某院2014年9月~2016年12月间收治。结果:两组患者治疗后观察组患者的ESR和CRP均明显较优;两组患者治疗后,观察组患者的治疗有效率95.0%明显较高(对照组为70.0%),组间比较P0.05,说明两组数据差异明显;两组患者的不良反应发生率均为2.5%,组间比较差异不具有统计学意义。结论:来氟米特单独及联合甲氨蝶呤对类风湿关节炎患者体征改善及血清CRP、ESR水平变化的影响均具有一定作用,其中来氟米特联合甲氨蝶呤治疗能够使得患者体征得到明显改善,其能够提高患者治疗的效果,对血清CRP、ESR水平变化的影响也更加积极,因此值得临床借鉴。     

云克联合甲氨蝶呤、来氟米特治疗类风湿关节炎的疗效分析

目的 分析云克联合甲氨蝶呤、来氟米特治疗类风湿关节炎的疗效及安全性.方法 将66例类风湿关节炎患者随机分为两组,观察组33例采用静脉滴注云克联合口服甲氨蝶呤、来氟米特治疗,对照组33例单纯口服甲氨蝶呤、来氟米特治疗.观察治疗后12周的关节症状、实验室指标变化,评价其疗效及不良反应.结果 治疗12周后,观察组关节症状、实验室指标与治疗前相比均显著改善,差异有统计学意义(P<0.05),而对照组仅个别实验室指标有所改善,差异有统计学意义(P<0.05);与对照组比较,观察组治疗后,相关指标均明显优于对照组,差异有统计学意义(P<0.05).两组均未出现严重不良反应,不良反应发生率,差异无统计学意义(P>0.05).结论 云克联合甲氨蝶呤、来氟米特治疗类风湿关节炎疗效显著、安全性好.     

来氟米特和白芍总苷联合甲氨蝶呤治疗类风湿关节炎的临床观察

目的评价来氟米特和白芍总苷联合甲氨蝶呤治疗类风湿关节炎的疗效和不良反应。方法回顾性分析我院2006年2月～2010年11月收治的110例类风湿患者临床资料,在常规用非甾体药的基础上,对照组仅用甲氨蝶呤,而治疗组加用来氟米特和白芍总苷。结果两组治疗前后各观察指标均比治疗前有明显改善(P<0.05),治疗组更显著。两组晨僵时间、关节疼痛数比较差异显著(P<0.05)。两组不良反应比较无差异。结论来氟米特和白芍总苷联合甲氨蝶呤治疗类风湿关节炎效果较好,不良反应少。     

来氟米特在风湿免疫性疾病及肾脏疾病中的临床应用

来氟米特作为一种新型免疫抑制剂,最初主要用于类风湿关节炎治疗.近年基础和临床研究表明,本品对其他风湿免疫性疾病和肾脏疾病等治疗具有较好的临床疗效.本文综述来氟米特相关临床应用研究.     

新型免疫调节剂--来氟米特

介绍了来氟米特（leflunomide）的药理学特征、临床应用及安全性评价。来氟米特是一种新型免疫调节剂，它对类风湿关节炎（RA）有很好的治疗效果，不良反应较小，具有较好的临床应用前景。     

甲氨蝶呤联合来氟米特治疗类风湿关节炎128例分析

目的:对在类风湿关节炎治疗中应用甲氨蝶呤联合来氟米特用药方案的临床疗效进行探究.方法:选择过去一年(2015年8月~2016年8月)在我院风湿免疫科接受治疗的128例类风湿关节炎患者进行回顾探究.依据随机数字表法以及治疗药物的不同将所有患者均分至单纯甲氨蝶呤治疗的单一组与甲氨蝶呤联合来氟米特治疗的联合组.对比二者不同用药方案的疗效.结果:采取甲氨蝶呤联合来氟米特治疗类风湿关节炎的联合组临床总有效率达92.19%,远远高于单一组的71.88%,P<0.05.在不良反应方面,二者差异无统计学意义.结论:对于关节炎采取甲氨蝶呤联合来氟米特治疗不仅临床效果佳,而且安全性高,应予推广.     

来氟米特与甲氨蝶呤对难治性类风湿关节炎的临床作用

目的:探讨分析来氟米特与甲氨蝶呤对难治性类风湿关节炎的临床作用与应用效果.方法:选取我院2016年2~10月收治的140例难治性类风湿关节炎患者作为研究对象,将其分为常规组和联合组,各70例,常规组给予来氟米特治疗,联合组给予来氟米特与甲氨蝶呤治疗,观察两组临床疗效.结果:联合组临床治疗总有效率与常规组比较,联合组明显高于常规组,有明显差异(P<0.05).治疗后两组关节疼痛肿胀指数、晨僵时间、ESR均比治疗前有明显变化,得到了很大改善,联合组常规组对比有明显差异(P<0.05).结论:来氟米特与甲氨蝶呤均能有效控制难治性类风湿关节炎的病情进展,有助于提高临床缓解率,适合病情较轻的患者,不良反应少,治疗效果显著,值得临床推广.     

Nanomedicines for the treatment of rheumatoid arthritis: State of art and potential therapeutic strategies

Increasing understanding of the pathogenesis of rheumatoid arthritis (RA) has remarkably promoted the development of effective therapeutic regimens of RA. Nevertheless, the inadequate response to current therapies in a proportion of patients, the systemic toxicity accompanied by long-term administration or distribution in non-targeted sites and the comprised efficacy caused by undesirable bioavailability, are still unsettled problems lying across the full remission of RA. So far, these existing limitations have inspired comprehensive academic researches on nanomedicines for RA treatment. A variety of versatile nanocarriers with controllable physicochemical properties, tailorable drug release pattern or active targeting ability were fabricated to enhance the drug delivery efficiency in RA treatment. This review aims to provide an up-to-date progress regarding to RA treatment using nanomedicines in the last 5 years and concisely discuss the potential application of several newly emerged therapeutic strategies such as inducing the antigen-specific tolerance, pro-resolving therapy or regulating the immunometabolism for RA treatments.KEY WORDS: Nanomedicines, Rheumatoid arthritis, Targeted drug delivery, Liposome, Micelle, Stimulus-responsive delivery systems, Immune tolerance, Inflammation resolution     

Design and development of an injectable in situ forming drug delivery system of methotrexate for the treatment of rheumatoid arthritis

Methotrexate (MTX) is the drug of choice for the treatment of rheumatoid arthritis (RA). At present there exists a lacuna in delivering methotrexate in suitable dosage form to maintain optimum plasma concentration to achieve therapeutic efficacy during the treatment period. Exposure of MTX at higher concentrations resulted in severe side effects. Moreover, the treatment modality (initial and maintenance dose) of RA is not clinically uniform. Biodegradable injectable in situ gels offer versatility in delivering drug at predetermined rates, and maintaining plasma concentration with a possibility of dose adjustment. They can be developed to optimize the therapeutic properties of a drug product, render them safe, effective and reliable during therapy. The aim of the present study was to formulate a biodegradable injectable in situ gel system for methotrexate sodium in the treatment of rheumatoid arthritis. The formulations were prepared by "cold technique" using thermosensitive polymer, Pluronic F-127 (20 %) and varying concentration of co-polymers, Pluronic F-68 (2–6 %) and Carbopol 934 (1.0-1.5 %). The prepared in situ gels were evaluated in vitro for drug interactions by FT-IR, sterility, gelation characteristics, content uniformity, viscosity, syringeability and in vitro drug release. MTX was evenly distributed in all formulations, which were sterile and syringeable through an 18 gauze needle. The gels were thermosensitive and thermoresponsive, and were dependent on the concentration of co-polymers. Drug release from in situ gels was sustained for 96 h to 120 h, and influenced by the type and concentration of co-polymers employed. Drug release was significantly higher in dynamic diffusion state in comparison with static state as ascertained by student t-test. The drug release was by non-fickian diffusion mechanism and followed first-order kinetics. These findings suggested that in situ gels can be effectively used to achieve controlled drug release; are easy to administer, are effective with reduced frequency of dosage, and result in increased patient compliance and comfort. It may be concluded that methotrexate in situ gels are ideally suitable in the treatment of RA.     

醋氯芬酸缓释片治疗类风湿关节炎有效性和安全性评价

目的:比较醋氯芬酸缓释片和阳性对照药醋氯芬酸片治疗活动期类风湿关节炎(RA)疗效和安全性。方法:采用随机、双盲双模拟、平行对照方法,选择疾病活动期RA患者45例(试验组22例,对照组23例);试验药醋氯芬酸缓释片200 mg,每天一次;对照药醋氯芬酸片100 mg,每天2次;4周为一疗程。结果:治疗4周后,试验组总有效率为63.6%,对照组总有效率69.6%(P>0.05)。两药均能显著改善RA患者的症状和体征(P<0.05)。不良反应发生率试验组为13.0%,对照组为12.0%,两组间不良反应发生率差异无统计学意义(P>0.05)。结论:醋氯芬酸缓释片治疗RA的疗效和安全性与醋氯芬酸片类似,但用药方便。     

Vasorelaxing effect of levosimendan against 5-hydroxytryptamine-induced contractions in isolated human conduit bypass grafts

Levosimendan is a novel inodilator drug developed for the treatment of heart failure. The possible vasodilating property of the drug in human coronary artery bypass grafts was investigated. Isometric tensions of the left internal thoracic artery (LITA, n = 8) as well as the proximal and distal segments of the radial artery (RA, n = 8 and 8) were measured in isolated organ baths. Concentration-relaxation curves for levosimendan (0.009-1.14 micromol L(-1)) were obtained against 5-hydroxytryptamine (5-HT; serotonin, 0.002-9.3 micromol L(-1))-induced contractions. 5-HT-induced contraction of LITA was considerably smaller than that of the proximal and distal RAs. Levosimendan relaxed the grafts in the following order of calculated maximum efficacies (E(max)): LITA > proximal RA > distal RA (LITA 100.3+/-16.2% of 5-HT-induced maximum tension, proximal RA 86.9+/-8.6%, distal RA 59.4+/-17.5%, P < 0.05 LITA vs distal RA). The potency values of levosimendan, expressed as the negative logarithm of 50% effective concentrations (pD(2)), were comparable in the three bypass grafts (LITA -6.52+/-0.44 log mol L(-1), proximal RA -6.60+/-0.49 log mol L(-1), distal RA -6.85+/-0.45 log mol L(-1)). The results suggest that levosimendan is an effective vasorelaxant of conduit bypass grafts and may serve as a new therapeutic tool, especially in the case of LITA and proximal RA grafts, for relieving perioperative spasm and subsequent graft failure.     

基因芯片技术用于中医药治疗类风湿性关节炎的研究进展

类风湿性关节炎(rheumatoid arthritis,RA)是一种致残率极高、临床治愈率低的自身免疫性疾病,被认为是一种多因素参与、多基因改变协同作用的结果.如何有效治疗RA值得医药界研究人员的探讨.随着中医药技术的发展,基因芯片技术已从基础研究逐步应用于新药研发和临床诊断,为进一步研究治疗RA提供了新的思路及方法...     

Drug delivery strategies for cathepsin inhibitors in joint diseases

Cathepsins play important roles in the development of joint and bone diseases such as osteoporosis, rheumatoid arthritis (RA) and osteoarthritis (OA). Cathepsin inhibitors are presently in development and clinical testing for use as novel disease-modifying drugs for the improved treatment of osteoporosis. They may also be applicable for the treatment of joint diseases. However, some barriers still hamper their clinical applications in these indications. Based on pathophysiological features of RA and OA, the authors discuss six potential drug delivery strategies for the effective delivery of cathepsin inhibitors or other antiarthritic drugs to the arthritic joint tissue. Successful application of these strategies may significantly contribute to a more effective and safe treatment of RA and OA.     

Drug delivery strategies for cathepsin inhibitors in joint diseases

Cathepsins play important roles in the development of joint and bone diseases such as osteoporosis, rheumatoid arthritis (RA) and osteoarthritis (OA). Cathepsin inhibitors are presently in development and clinical testing for use as novel disease-modifying drugs for the improved treatment of osteoporosis. They may also be applicable for the treatment of joint diseases. However, some barriers still hamper their clinical applications in these indications. Based on pathophysiological features of RA and OA, the authors discuss six potential drug delivery strategies for the effective delivery of cathepsin inhibitors or other antiarthritic drugs to the arthritic joint tissue. Successful application of these strategies may significantly contribute to a more effective and safe treatment of RA and OA.     

~(99)Tc-亚甲基二膦酸盐治疗类风湿关节炎的体会

目的 了解国产新药９９ＴＣ－亚甲基二膦酸盐（９９ＴＣ－ＭＤＰ）治疗类风湿关节炎（ＲＡ）的疗效和安全性。方法９９Ｔｃ．ＭＤＰ ２００ ｍｇ＋０．９％氯化钠溶液２５０ｍｌ静脉滴注,每日１次,连用５次为１疗程,间隔５ｄ后应用第２疗程;平均应用（３．８±１．６）疗程。结果 ２２例 ＲＡ治疗８周后,显效８例,有效１２例,无效２例。无明显毒副作用,安全性好。对ＲＡ患者的关节肿痛及晨僵有显著改善,但对类风湿因子、血沉（反应蛋白及握力无明显影响。结论９９Ｔｃ－ＭＤＰ治疗ＲＡ,疗效好,安全性亦好。     

Current concepts in the treatment of rheumatoid arthritis

The treatment of RA is complex and often frustrating. The pathologic process of RA is composed of acute inflammation, chronic immunologic phenomenon, and chronic connective tissue degradation. It is important to understand not only the pathophysiology of RA but also the mechanism of action of our therapeutic drugs so that treatment can be tailored to affect the important aspects of the process leading to end-organ damage. Despite the many drugs available, therapy is still unsatisfactory. Many drugs work in only certain patients. This could be secondary to variability in the disease state or to difference in drug metabolism. A better understanding of both disease and therapeutic agents may lead to better use of our present agents and development of new, more effective treatment modalities.     

脉血康胶囊联合甲氨蝶呤治疗类风湿性关节炎的临床观察

目的：观察脉血康胶囊联合甲氨蝶呤治疗类风湿性关节炎（RA）的临床疗效和安全性。方法：将65例RA患者按随机数字表法分为两组。对照组（30例）患者给予甲氨蝶呤10mg,每周1次;治疗组（35例）患者在对照组治疗基础上加用脉血康胶囊1000mg,tid。两组疗程均为30d。观察两组患者临床疗效和临床症状、体征及实验室指标改善情况,以及治疗过程中不良反应发生情况。结果：治疗后,治疗组患者的总有效率为91．4％,显著高于对照组（70．0％）,两组比较差异有统计学意义（P〈0．05）;治疗组患者在肿胀关节数、压痛关节数、红细胞沉降率、C反应蛋白、血小板计数等方面的改善均显著优于对照组,两组比较差异有统计学意义（P〈0．05）;两组患者不良反应发生率比较,差异无统计学意义（P〉0．05）。结论：脉血康胶囊联合甲氨蝶呤治疗RA疗效较好,可显著改善RA患者的临床症状以及实验室指标,且不增加不良反应的发生。