瑞格列奈和那格列奈治疗2型糖尿病安全性的Meta分析

目的：评价瑞格列奈和那格列奈治疗2型糖尿病的安全性。方法：检索Pub Med,Medline,Cochrane,EMbase,CNKI,VIP,万方等文献数据库,根据纳入标准对文献进行筛选和评估,采用Rev Man 5.2软件对数据进行Meta分析。结果：经筛选最终纳入10项研究,共计2300例患者,其中瑞格列奈组1150例,那格列奈组1150例。Meta分析结果显示：在降低患者糖化血红蛋白[MD=–0.23,95%CI（–0.34,–0.12）,P〈0.000 1]和空腹血糖水平[MD=–0.16,95%CI（–0.24,–0.07）,P=0.000 3]方面,瑞格列奈组优于那格列奈组;在降低餐后2小时血糖[MD=0.10,95%CI（–0.29,0.48）,P=0.63]水平方面,两组没有统计学差异;瑞格列奈组在低血糖反应[OR=1.92,95%CI（1.16,3.20）,P=0.01]和胃肠道反应[OR=2.64,95%CI（1.09,6.39）,P=0.03]方面的发生风险高于那格列奈组,而两组在肝功能异常[OR=3.02,95%CI（0.61,15.01）,P=0.18]、过敏反应[OR=0.28,95%CI（0.06,1.36）,P=0.12]和心血管系统[OR=0.60,95%CI（0.22,1.65）,P=0.32]方面的不良反应发生风险相似。结论：瑞格列奈的降糖作用优于那格列奈,同时其低血糖和胃肠道反应的发生风险也相对较高。由于本研究存在一定的局限性,因此结论的可靠性仍需多中心、大样本、高质量的RCT加以验证。     

Development and in vitro/in vivo evaluation of controlled release provesicles of a nateglinide–maltodextrin complex

The aim of this study was to characterize the provesicle formulation of nateglinide (NTG) to facilitate the development of a novel controlled release system of NTG with improved efficacy and oral bioavailability compared to the currently marketed NTG formulation (Glinate™ 60). NTG provesicles were prepared by a slurry method using the non-ionic surfactant, Span 60 (SP), and cholesterol (CH) as vesicle forming agents and maltodextrin as a coated carrier. Multilamellar niosomes with narrow size distribution were shown to be successfully prepared by means of dynamic laser scattering (DLS) and field emission scanning electron microscopy (FESEM). The absence of drug-excipient interactions was confirmed by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. In vitro release of NTG in different dissolution media was improved compared to pure drug. A goat intestinal permeation study revealed that the provesicular formulation (F4) with an SP:CH ratio of 5:5 gave higher cumulative amount of drug permeated at 48 h compared to Glinate™ 60 and control. A pharmacodynamic study in streptozotocin-induced diabetic rats confirmed that formulation F4 significantly (P<0.05) reduced blood glucose levels in comparison to Glinate 60. Overall the results show that controlled release NTG provesicles offer a useful and promising oral delivery system for the treatment of type II diabetes.KEY WORDS: Provesicles, Niosomes, Maltodextrin, Nateglinide, In vitro release, Goat intestinal permeation, Hypoglycemic     

HPLC法测定那格列奈含量及有关物质

目的建立那格列奈含量及有关物质的HPLC测定方法。方法以C18柱,磷酸盐缓冲液(pH 3.0)-乙腈(50∶50)为流动相,流量为1.0 ml.min-1,柱温30℃,检测波长为210 nm。结果在浓度为0.0601~1.8030μg范围线形关系良好,相关系数r=0.9993(n=6),重复性试验的RSD为0.9%(n=6)。有关物质分离较好。结论本方法简单、准确,可作为那格列奈含量和有关物质的测定方法。     

甘精胰岛素联合那格列奈与胰岛素泵对2型糖尿病骨折患者围手术期的疗效观察

分析甘精胰岛素联合那格列奈和胰岛素泵治疗2型糖尿病骨折患者围手术期的资料,发现两种治疗均能使血糖达标[空腹血糖(6.89±1.96)对(6.75±2.33)mmol/L],达标时间无显著差异[(3.6±1.6)对(2.9±1.2)d,均P0.05],但胰岛素泵组的平均血糖值更低.     

那格列奈对初诊2型糖尿病患者炎性反应状态的影响

目的探讨那格列奈治疗初诊2型糖尿病对患者炎性反应状态的影响。方法回顾性分析采用那格列奈治疗的74例初诊2型糖尿病患者的临床资料,观察患者治疗前、治疗后的空腹血糖（FBG）、餐后0．5h血糖（0．5hPG）、餐后1h血糖（1hPG）、餐后2h血糖（2hPG）、空腹胰岛素（FINS）、餐后0．5h胰岛素（0．5biNS）、餐后1h胰岛素（1bINS）、餐后2h胰岛素（2hlNS）、白细胞介素-2（IL-2）及C反应蛋白（CRP）水平变化情况。结果治疗后,患者的FBG、0．5hPG、1hPG、2hPG、FINS、0．5hlNS、1hlNS、2bINS、IL-2及CRP分别为（8．0±1．5）mmol／L、（12．0±1．8）mmol／L、（10．2±1．3）mmol／L、（10．5±1．2）mmol／L、（168．2±11．5）pmol／L、（213．5±23．5）pmol／L、（197．0±21．5）pmol／L、（189．5±12．0）pmol／L、（14．0±1．5）斗g／／L、（13．5±1．5）mg／L,较治疗前的（10．5±1．0）mmol／L、（14．5±1．5）mmol／L、（12．5±1．4）rnmol／L、（11．6±2．0）mmol／L、（180．7±12．0）pmol／L、（229．8±26．0）pmol／L、（218．5±23．0）pmol／L、（197．0±14．5）pmol／L、（12．5±2．0）彬L、（22．8±2．0）mg／L均明显下降（t=11．9293、9．1785、10．3561、4．1115、6．4696、4．0009、5．8744、3．4279、5．2307、32．0006,均P〈0．05）,治疗过程中无严重不良反应发生。结论那格列奈治疗初诊2型糖尿病能够明显改善患者的炎性反应状态,且治疗过程中无严重不良反应。‘     

那格列奈对新诊断2型糖尿病患者炎性反应状态的影响

目的探讨那格列奈对新诊断2型糖尿病患者炎性反应状态的影响。方法 40例新诊断2型糖尿病患者分为那格列奈组（观察组,20例）和生活方式调整组（对照组,20例）,检测治疗前及治疗12周后的血脂、糖化血红蛋白（HbA（1c））、白介素-2（IL-2）及C反应蛋白（CRP）的变化。结果治疗后2组各项指标均显著改善（P〈0.05）,而除HbA（1c）外观察组患者的血脂、IL-2和CRP均明显低于对照组（P〈0.05）。结论那格列奈可以改善新诊断2型糖尿病患者的炎性反应状态,可能与糖脂毒性的改善有关。     

Determination of the nateglinide polymorphic purity through DSC

It is well known that the control of the crystallization of drugs to ensure that only the approved and desired polymorph is present in the formulation is a crucial point of a preformulation study. In this regard, the aim of the present work is to devise a method for the quantification of the polymorphic purity of nateglinide in mixtures formed by polymorphs H and B. In order to achieve this goal, binary systems of known composition have been prepared and the melting peaks of both polymorphs have been recorded by differential scanning calorimetry. Experiments have determined that the method of preparation of the mixtures has to be carefully evaluated. Indeed it has been shown that grinding the samples induces transition from B to H form. Furthermore, it could be observed that the enrichment of the binary mixture with H form is caused by heating. Therefore, after having prepared the mixture without grinding stage, we propose a method to evaluate the content of H polymorph in mixture with the B one from the melting peak of B.     

那格列奈联合二甲双胍治疗初发2型糖尿病的临床观察

目的：比较那格列奈联合二甲双胍与单用二甲双胍治疗初发型2型糖尿病的疗效,不良反应及对胰岛β细胞功能的影响。方法：将120例初发2型糖尿病患者随机分为那格列奈＋二甲双胍组（68例）和二甲双胍组（52例）观察12周,比较二组治疗前、后血糖控制情况（糖化血红蛋白7次血糖）、胰岛素用量、低血糖发生率、空腹C肽、餐后2h C肽的变化。结果：那格列奈＋二甲双胍和单用二甲双胍具有显著的降低血糖和改善胰岛β细胞分泌的作用,治疗前、后比较差异有统计学意义（P〈0．01）,那格列奈＋二甲双胍的3餐后血糖得到明显改善．低血糖发生率增加一半,差异有统计学意义（P〈0．01）,两组患者未观察到明显不良反应。结论：那格列奈＋二甲双胍能更好地控制餐后血糖,但比单用二甲双胍有增加餐后低血糖的风险。     

Stability-indicating HPTLC method for simultaneous determination of nateglinide and metformin hydrochloride in pharmaceutical dosage form

A stability indicating high performance thin layer chromatography (HPTLC) method was developed and validated for determination of two anti-diabetic drugs, nateglinide and metformin hydrochloride in co-formulations. Study was performed on pre-coated silica gel HPTLC plates using chloroform:ethyl acetate:acetic acid (4:6:0.1 v/v/v) as the mobile phase. A TLC scanner set at 216 nm was used for direct evaluation of the chromatograms in the reflectance/absorbance mode. Method was validated according to ICH guidelines. The correlation coefficients of calibration curves were found to be 0.996 and 0.995 in the concentration range of 200–2400 and 500–3000 ng band⁻¹ for nateglinide and metformin, respectively. The method had an accuracy of 99.72% for nateglinide and 100.08% for metformin hydrochloride. The method had the potential to determine these drugs simultaneously from dosage forms without any interference of the tablets excipients. Nateglinide and metformin hydrochloride were also subjected to acid, base, oxidation, wet, heat and photo-degradation studies. The degradation products obtained were well resolved from the pure drugs with significantly different R_f values. As the method could effectively separate the drugs from its degradation products, it can be used for stability-indicating analysis.     

那格列奈片的高效液相色谱分析

目的:建立那格列奈片中主药那格列奈及杂质的高效液相色谱测定方法。方法:采用Shim-Pack CLC-ODS(150mm×6.0mm)色谱柱,甲醇-0.02mol.L~(-1)磷酸盐缓冲液(pH6.6)(75:25)作流动相,检测波长210nm,含量测定采用外标法, 杂质检查采用面积归一化法。考察了不同流动相下那格列奈的色谱行为及其与杂质的分离情况。结果:在优化的色谱条件下,片剂辅料不干扰测定,有关杂质与主药那格列奈分离良好,那格列奈线性范围5.1～101.0 mg·L~(-1),最低检测限0.2 mg·L~(-1),含量测定的回收率99.4％～100.4％,RSD<1.7％。结论:此法简便,准确,专属性强,重现性好,可用于那格列奈片的质量控制、稳定性考察和有效期预测。