反相高效液相色谱法测定米格列醇片的有关物质

目的：建立一种简便、准确的方法（RP-HPLC法）测定米格列醇片的有关物质。方法：采用反相高效液相色谱法,用自身对照法计算米格列醇片有关物质的量。用AstecCYCLOBONDI2000（250mm×4.6mm,5μm）色谱柱,以0.115%磷酸二氢钠（NaH2PO4·H2O）溶液-乙腈（20：80）为流动相,于波长为205nm处检测。结果：米格列醇与其杂质完全分离,有关物质的线性回归方程为：A=5.22×103C＋2.52×103,r=0.9999（n=5）;方法的最低检出限为3.836ng。结论：实验证明该法简便快捷,能准确地测定样品的有关物质。     

HPLC法测定米格列醇片的含量

目的建立米格列醇片含量测定的高效液相色谱法。方法采用氨丙基键合硅胶色谱柱(4.6 mm×250mm,5μm),以0.025 mol.L-1磷酸二氢钾溶液-乙腈(30∶70)为流动相;流速1.0 mL.min-1;柱温40℃;检测波长为210 nm。结果线性范围为0.2～0.6 mg.mL-1,r=0.999 7;平均回收率为100.6%,RSD为1.7%(n=9)。结论本法专属性强、准确度好、简便、快速。     

Design and evaluation of oral bioadhesive controlled release formulations of miglitol, intended for prolonged inhibition of intestinal α-glucosidases and enhancement of plasma glucagon like peptide-1 levels

α-Glucosidase enzyme is present ubiquitously throughout the lumen of the small intestine. It is responsible for the breakdown of complex into simple carbohydrates. α-Glucosidase inhibitors such as miglitol, are drugs that have greater affinity towards this enzyme in comparison to carbohydrates. Miglitol regulates the postprandial glucose levels directly by inhibiting the enzyme reversibly and also indirectly by including the secretion of glucagon like peptide-1 (GLP-1). The aims of this study were (i) to design a controlled release (CR) mucoadhesive (in the intestine) formulation of miglitol which would inhibit the α-glucosidase enzyme for a longer duration of time (in comparison to the non-controlled release (IR) formulation) thus reducing the dosing frequency, and also controlling the postprandial glucose levels more effectively over a longer period of time; (ii) to assess the effect of different formulation parameters on the release of miglitol in vitro from the CR pellets; (iii) to evaluate the mucoadhesion of pellets in the intestine ex vivo; (iv) to study the effect of formulation parameters on plasma GLP-1 levels; and (v) to find out the effect of formulations on postprandial glucose levels. The data obtained was analysed to find out whether there was a correlation between these different parameters. Four controlled release formulations (CR1, CR2, CR3 and CR4) of miglitol comprising of multilayered pellets were designed successfully. The CR4 formulation containing 30% of 20 cps of ethyl cellulose (the retarding layer of the formulation) displayed slowest release of miglitol in vitro in comparison to other formulations. We designed an ex vivo experimental setup for studying the mucoadhesion of the pellets in the lumen of the intestine. Results indicated that amongst all of the adherent pellets, 5% were found to be adhering in the duodenal region, 61% in the jejunum, 32% in the ileum and 2% in the colon. Two of the controlled release formulations CR1 and CR4 were evaluated in vivo in dogs. Both the formulations displayed significantly higher and more prolonged (greater AUC) levels of GLP-1 in comparison to either the placebo or the immediate release (IR) formulations. They even displayed a significantly better control of postprandial glucose in comparison to either placebo or IR formulations. However, a comparison between the two controlled release formulations (CR1 and CR4) revealed that the plasma GLP-1 (AUC by CR1 = 63.1 ± 1.32 and CR4 = 66.2 ± 0.82) and postprandial glucose values due to both the formulations were rather similar despite their differences in in vitro release as well as pharmacokinetic profiles (plasma miglitol AUC of CR1 = 16.17 ± 4.11 and CR4 = 27.17 ± 4.33).     

HPLC-示差折光检测器测定米格列醇片的含量及有关物质

目的建立高效液相色谱-示差折光检测法测定米格列醇片的含量和有关物质。方法用磺酸基阳离子交换键合硅胶(250×4.6mm,5μm)为填充剂;以乙腈-三氟乙酸溶液(4.5→1000mL)(20∶80)为流动相;示差折光检测器检测;检测器温度为40℃。理论板数以米格列醇峰计算,应不低于2000。结果空白辅料不干扰测定,米格列醇主峰和杂质峰分离良好,定量限浓度约为10μg·mL^-1。米格列醇浓度在26.28~210.2μg·mL^-1范围内,与峰面积线性关系良好,线性方程A=2611.5C-2802,r=0.9988;平均回收率100.9%(RSD=1.0%;n=9);溶液在8h内稳定。结论本法专属性强、灵敏度高、准确度和稳定性好,可作为米格列醇片有关物质和含量测定的检测方法。     

Amplification of the inhibitory activity and reversal of the selectivity of miglitol by C(2')-monofluorination

Selective monofluorination of the α-glycosidase inhibitor and antidiabetic agent miglitol at positions C(2') or C(6) creates competitive inhibitors of glycosidases. Introducing a fluorine substituent at position C(6) results in a reduced binding to the enzyme whereas fluorination at C(2') produces an inhibitor with an activity four times higher than the parent compound. This compound is selective for the α-galactosidase from green coffee beans. Its screening against a panel of human cell lines showed a low cytotoxicity, therefore, making this compound an interesting candidate for further clinical investigations.     

Effects of miglitol taken just before or after breakfast on plasma glucose,serum insulin,glucagon and incretin levels after lunch in men with normal glucose tolerance,impaired fasting glucose or impaired glucose tolerance

Aims/Introduction: One of the reasons for the poor adherence to α‐glucosidase inhibitor (αGI) treatment is the need to take medication three times a day. We hypothesized that the administration of miglitol might be effective for the next meal if the miglitol‐induced inhibition of α‐glucosidase activity persists until the next meal. In the present study, we evaluated whether the administration of miglitol just before or after breakfast was effective for postprandial glucose excursion after lunch without taking miglitol at lunch. Materials and Methods: We measured the plasma glucose, serum insulin and glucagon, plasma active glucagon‐like peptide‐1 (GLP‐1), and total glucose‐dependent insulinotropic polypeptide levels in non‐diabetic men. Miglitol was given to each patient according to four different intake schedules (control: no drug; intake 1: drug given just before breakfast [50 mg]; intake 2: drug given 30 min after the start of breakfast [50 mg]; intake 3: drug given at the same time as intake 2, but without eating breakfast [50 mg]). Results: Both intake 1 and intake 2 had a smaller area under the curve (AUC) for plasma glucose excursion after lunch, compared with the control. Intake 2 had a larger AUC for active GLP‐1 after lunch, compared with intake 1. Conclusions: Intake 1 and intake 2 can improve postprandial hyperglycemia after lunch. The results of the present study raise the possibility that the administration of miglitol twice a day might be effective and might help to improve treatment adherence among diabetic patients. This trial was registered with UMIN Clinical Trial Registry (no. UMIN000002896). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00129.x, 2011)     

米格列醇对2型糖尿病患者尿蛋白排泄率的影响

目的观察米格列醇对2型糖尿病患者的疗效及对患者尿微量白尿蛋白排泄率的影响。方法对根据WHO的诊断标准确诊为2型糖尿病的初治患者,先采用经饮食控制、运动治疗或同时进行1个月以上,对符合纳入标准的60例初治患者,随机分为米格列醇组和格列喹酮组,疗程3个月,治疗期间,每月随访1~2次,检测相关指标。结果两种药物均具有较好的降血糖作用;组内比较结果显示,米格列醇和格列喹酮均可以降低早期糖尿病患者的尿微量白蛋白排泄率,差异有统计学意义（P〈0.05）,两组间比较,结果无统计学意义（P〉0.05）;两组治疗前后尿素氮、肌酐的差异均无显著性（P〉0.05）。结论米格列醇具有良好的降糖功能,还能降低糖尿病患者的尿微量白蛋白排泄率,对早期的DN患者起到一定的保护作用。     

米格列醇与阿卡波糖治疗2型糖尿病的药物经济学研究

目的:比较米格列醇与阿卡波糖治疗2型糖尿病的药物经济学效果。方法:将2017年9月至2018年8月解放军第910医院门诊收治的2型糖尿病患者100例按就诊顺序分为两组,单号为米格列醇组,双号为阿卡波糖组,每组50例。米格列醇组患者口服米格列醇片治疗,阿卡波糖组口服阿卡波糖片治疗。两组患者均联合二甲双胍治疗,疗程为12周。观察两组患者治疗前后空腹血糖(FBG)、餐后2 h血糖(2 hPBG)及糖化血红蛋白(HbA1c)水平,并以FBG、2 hPBG及HbA1c水平评估疗效,运用药物经济学原理进行成本-效果分析。结果:治疗12周后,两组患者FBG、2 hPBG及HbA1c水平均较治疗前明显降低,且米格列醇组患者上述指标水平降低程度较阿卡波糖组更为明显,差异均有统计学意义(P<0.05)。米格列醇组方案上述3项指标疗效的成本-效果比均低于阿卡波糖组,且阿卡波糖组方案相对于米格列醇组的增量成本-效果比分别为26.04、39.06和11.16。米格列醇组、阿卡波糖组患者的不良反应发生率分别为4.0%(2/50)、8.0%(4/50),差异无统计学意义(P>0.05)。结论:米格列醇能明显降低2型糖尿病患者FBG、2 hPBG和HbA1c水平,临床疗效显著,不良反应少,具有药物经济学优势。     

米格列醇与阿卡波糖治疗2型糖尿病的临床疗效及不良反应比较

目的对米格列醇与阿卡波糖治疗2型糖尿病的疗效及不良反应进行评价比较。方法选择我院2012年11月至2013年12月住院治疗的2型糖尿病患者80例,随机分为米格列醇组和阿卡波糖组,每组40例,比较治疗前及1、2、3个疗程过程中的血糖、血脂等指标的变化,并记录不良反应发生率。结果两种药物均具有较好的降血糖作用,尤其对餐后高血糖症状缓解较为明显,第3个疗程结束后,两组患者的HbA1c均降低,但是米格列醇组较阿卡波糖组尤为明显,差异有统计学意义(P<0.05);两组患者的TG较治疗前显著降低,HDL显著升高,差异有统计学意义(P<0.05),但TC的变化不显著。整个治疗过程中,两组患者都有不同程度的胃肠道不良反应,但米格列醇组较轻微,随着用药时间延长,这些症状均会缓解,未见严重不良反应现象。结论阿卡波糖和米格列醇均为一种安全有效的口服降糖药物,米格列醇略优。     

米格列醇的临床不良反应及合理用药

目的分析米格列醇不良反应（ADR）发生的类型及特点,为临床合理用药提供参考。方法系统回顾国内外近十年来有关米格列醇不良反应的文献报道。结果米格列醇的不良反应主要为肠壁囊样积气症,低血糖,胃肠道反应和皮疹。结论临床医师及药师应重视米格列醇的不良反应,以保证患者用药安全。