复方降糖合剂Ⅰ和Ⅱ的制备及临床应用

目的：研究中药制剂复方降糖合剂Ⅰ和Ⅱ的制备及临床应用.方法：拟定制剂的配制工艺,并进行性状、检查等质量研究,采用薄层色谱法对其有效成分进行鉴别;建立治疗组和对照组,观察空腹血糖、糖化血红蛋白、血脂等,研究治疗组的疗效、不良反应发生率及治疗费用.结果：确定复方降糖合剂Ⅰ和Ⅱ的质量标准;治疗组和对照组疗效相当,而治疗组的不良反应发生率及治疗费用比对照组低.结论：复方降糖合剂Ⅰ和Ⅱ的配制工艺合理,质量稳定可控;在治疗糖尿病中,与单用西药相比有不良反应少、患者费用低的优势.     

降糖合剂的薄层色谱鉴别

目的：对降糖合剂的质量进行控制。方法：采用薄层色谱法对处方中的黄芪、制何首乌进行鉴别。结果：薄层色谱上均出现制剂中2种药材（黄芪、制何首乌）的特征斑点,空白对照色谱中无此斑点。结论：该法操作简单,重复性好,可作为该制剂质量控制的方法。     

淫羊藿总黄酮对四氧嘧啶糖尿病小鼠降糖作用的研究

目的 探讨淫羊藿总黄酮对四氧嘧啶所致糖尿病小鼠的降糖作用.方法 以200 mg·kg-1的剂量给小鼠腹腔注射四氧嘧啶造成糖尿病模型,按照50 mg·kg-1、100 mg·kg-1的剂量连续灌胃14 d后,取血测空腹血糖、SOD、MDA,并测定肝糖原和肌糖原含量,同时进行糖耐量实验.结果 淫羊藿总黄酮能够降低糖尿病小鼠...     

复方地黄合剂及复方逍遥合剂中黄芩苷含量测定

目的 :建立复方地黄合剂及复方逍遥合剂中黄芩苷含量的测定方法.方法 :采用高效液相色谱(HPLC)法、C18色谱柱(4.6 mm×250 mm,5μm)、流速1.2 ml/min,柱温25℃,波长280 nm测定,流动相为乙腈-0.2%磷酸溶液(27:73).结果 :在不同中药制剂中,黄芩苷峰形良好,方法专属性强.在浓度为16~320μg/ml范围内均呈良好的线性关系(r=0.9993);在50%、100%、150%的浓度下,二制剂中黄芩苷的回收率分别为99%及97%,RSD分别为1.7%和1.6%.此外,黄芩苷在8 h内含量变化的RSD分别为0.3%和0.2%,稳定性良好.结论 :该方法简便、准确、灵敏度高、重复性好,可用于复方地黄合剂及复方逍遥合剂中黄芩苷的含量的测定.     

香蕉皮多糖的降血糖效果研究

目的：研究香蕉皮多糖对糖尿病（DM）小鼠的降血糖作用。方法：四氧嘧啶溶液（200m g/kg w t）建立DM模型,不同剂量香蕉皮多糖连续给药14d,检测体重、血糖变化情况。结果：香蕉皮多糖能使DM小鼠血糖和体重维持在正常范围内。结论：香蕉皮多糖在DM降糖方面有很好的疗效。     

玉棠饮降糖活性研究

目的：研究玉棠饮的降糖作用,探讨作用机制。方法：用肾上腺素致高血糖小鼠模型评价玉棠饮的降糖效果,采用四氧嘧啶糖尿病小鼠模型进行验证,测定血糖含量、肝糖原含量、α-葡萄糖苷酶活性。结果：玉棠饮高、中、低剂量组能降低血糖,提高肝糖原含量,抑制α-葡萄糖苷酶活性,与模型组比有显著性差异（P〈0.05或P〈0.01）。结论：玉棠饮具有降糖作用,其降糖机制可能与抑制α-葡萄糖苷酶活性、抑制氧化应激对胰岛β细胞损伤,促进糖代谢有关。     

复方降糖滴丸质量标准研究

目的 建立复方降糖滴丸的质量标准。方法 采用薄层色谱法对滴丸中的栀子、绞股蓝进行定性鉴别,HPLC测定滴丸中栀子苷的含量,采用UV分别测定绞股蓝总皂苷和总多糖的含量。结果 定性鉴别结果斑点圆整,分离度好,易于鉴别;栀子苷的线性范围为3.99~255.20 μg·mL^-1,r=0.999 8,回收率为99.4%,RSD为2.9%;绞股蓝总皂苷的线性范围为17.00~134.00 μg·mL^-1,r=0.999 5,回收率为98.4%,RSD为2.9%;绞股蓝总多糖线性范围为12.56~62.80 μg·mL^-1,r=0.999 3,回收率为98.9%,RSD为2.4%。结论 本试验首次建立了复方降糖滴丸的质量标准,方法简便、准确、专属性强,可用于复方降糖滴丸的质量控制。     

复方降糖滴丸的成型工艺研究

目的应用固体分散体制备复方降糖滴丸,确定滴丸的最佳工艺条件。方法采用正交试验法,以提取物与基质配比、料液温度、冷凝剂为考察因素．以滴丸的外观质量、丸重变异系数、溶散时限为考察指标,优选复方降糖滴丸制备工艺。结果最佳工艺条件为提取物与基质比例为1：12,液体石蜡与甲基硅油比例为1：2,料液温度为85℃。结论正交试验确定的最佳工艺条件合理可行。     

复方甘草合剂的稳定性考察

目的:考察医院自制复方甘草合剂的稳定性.方法:通过加速试验和室温留样,采用HPLC法测定复方甘草合剂中甘草酸的含量,观察合剂外观性状并测定PH值.结果:在(20±2℃和40℃条件下,甘草酸的含量在0、1、2、3、6月符合规定,合剂的性状有轻微改变;常温放置40天,pH值符合正常范围.结论:复方甘草合剂性能稳定,在有效期内能保证患者用药安全.     

Gliclazide: pharmacokinetic-pharmacodynamic relationships in rats

The relationship between the pharmacokinetics of gliclazide and its antidiabetic efficacy were evaluated on the basis of experimental determination of changes with time in the plasma levels of this antidiabetic agent and those of glucose. The experiment included rats with both initial normal glycaemia and alloxan-induced hyperglycaemia (glycaemia increased by a minimum of 30%). Pharmacokinetic and pharmacodynamic parameters were examined in the interval of 30 to 180 min after p.o. administration of a single dose of 25 mg/kg of gliclazide. The drug was administered on day 4, following a single i.v. dose of either 50 mg/kg of alloxan (hyperglycaemic group) or the injection vehicle (control group). Even though the biological availability of gliclazide was similar in both normoglycaemic and hyperglycaemic animals, the gliclazide-induced hypoglycaemizing response was not uniform: until 60 min, the decrease of glycaemia was smaller in animals with alloxan hyperglycaemia (23% decrease at 60 min) in contrast to the normoglycaemic animals (36% decrease at 60 min), at later times, the intensity of this hypoglycaemizing effect of gliclazide persisted in the hyperglycaemic animals, while in the normoglycaemic ones, a reversal of the hypoglycaemizing effect occurred.     

太子参多糖对四氧嘧啶糖尿病小鼠的治疗作用

目的观察太子参多糖对四氧嘧啶糖尿病小鼠的治疗作用。方法选用雄性小鼠,尾静脉注射四氧嘧啶90 mg.kg-1建立小鼠糖尿病模型,太子参多糖按0.375、0.75、1.5 g.kg-1三种剂量给药,测定了糖尿病小鼠体重、空腹血糖、肝糖原含量以及免疫器官脾脏和胸腺的脏体指数。结果太子参多糖可显著降低糖尿病小鼠血糖,增加体重,增加肝糖原含量,增加脾脏和胸腺指数。结论太子参多糖对糖尿病小鼠具有显著的治疗作用。     

不同糖尿病模型小鼠糖原代谢变化的研究

目的:通过观察不同类型糖尿病动物模型糖原代谢的变化,初步探讨糖原代谢异常在糖尿病发病过程中的作用.方法:首先建立4种糖尿病小鼠模型:四氧嘧啶诱导模型、STZ诱导模型、n5-STZ诱导模型和葡萄糖激酶基因敲除模型,并对模型小鼠血糖水平进行检测.然后测定上述动物模型肝糖原和肌糖原的含量,并采用Western blot方法对葡萄糖激酶基因敲除模型鼠肝组织中葡萄糖激酶的蛋白表达量进行测定.结果:血糖检测结果显示各模型组空腹血糖值均显著高于对照组,表明糖尿病造模基本成功.除n5-STZ诱导模型外,其它模型组肝糖原的含量均明显低于对照组.此外,与对照组比较,4种糖尿病模型肌糖原含量均显著降低.Western blot结果表明葡萄糖激酶基因敲除模型鼠肝组织中葡萄糖激酶的蛋白表达显著降低,这可能是该模型肝糖原含量减少的机制之一.结论:糖尿病动物模型出现糖原代谢异常,表现为肝糖原和肌糖原减少,提示糖原代谢在糖尿病发病过程中起着重要的作用.     

壳寡糖降血糖作用的实验研究

目的：探讨壳寡糖的降血糖作用.方法：以尾静脉注射四氧嘧啶建立糖尿病大鼠模型,随机分为模型对照组,壳寡糖高、中、低剂量组,二甲双胍组和正常对照组,每组6只.观察壳寡糖对糖尿病大鼠血糖、胰岛素的影响及病理改变,观察壳寡糖对正常小鼠血糖及糖耐量的影响.结果：壳寡糖中、高剂量组均有明显降低四氧嘧啶糖尿病大鼠血糖作用（P＜0.05）.壳寡糖改善模型对照组大鼠胰腺功能,3个剂量组壳寡糖使血中胰岛素有升高趋势,但与模型对照组比较差异无统计学意义.壳寡糖低、中、高剂量组与空白对照组小鼠血糖比较差异无统计学意义（P＞0.05）,中、高剂量壳寡糖使小鼠灌胃葡萄糖后0.5 h血糖降低,与空白对照组比较差异有统计学意义（P＜0.05）.结论：壳寡糖具有明显降血糖作用,对正常小鼠血糖无影响,增加小鼠糖耐量作用.     

菟丝子多糖对糖尿病小鼠的治疗作用

目的观察菟丝子多糖对四氧嘧啶致糖尿病小鼠的治疗作用。方法四氧嘧啶制作糖尿病小鼠模型，测定小鼠体重、空腹血糖，肝糖原含量，并进行小鼠游泳试验、免疫器官脾脏和胸腺称重，观察菟丝子多糖150300、600mg·kg^-1对这些指标的影响。结果菟丝子多糖对糖尿病小鼠能显著降低血糖、增加体重、增加肝糖原含量、延长游泳时间、增加脾脏和胸腺重量。结论菟丝子多糖对四氧嘧啶糖尿病小鼠具有良好的治疗作用。     

Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabetics

Steviol glycosides, isolated from the plant Stevia rebaudiana (Bertoni) Bertoni, have been used as safe sweetening agents for more than 30 years. Beneficial effects of high doses of steviol glycosides on hyperglycemia and hypertension have been previously described when these abnormalities are present. This study was designed to evaluate the effects of steviol glycosides on blood glucose and on blood pressure (BP) in 3 groups of individuals. This was a randomized, double-blind, placebo-controlled, long-term study in three groups of patients: Group 1: subjects with Type 1 diabetes; Group 2: subjects with Type 2 diabetes; and Group 3: subjects without diabetes and with normal/low-normal BP levels. The subjects in each group were randomly allocated to active treatment (the steviol glycoside stevioside: 250mg t.d.s.) or to placebo treatment and followed-up for 3 months. Post-treatment systolic BP, diastolic BP, glucose and glycated hemoglobin (HbA1c) were not significantly different from baseline measurements, except for the placebo Type 1 diabetics group where a significant difference was observed for systolic BP and glucose. No side effects were observed in the two treatment groups. This study shows that oral steviol glycosides, taken as sweetener are well tolerated and have no pharmacological effect.     

Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitus

Objectives In rats with diabetes mellitus induced by alloxan (DMIA) or streptozocin (DMIS), changes in the cytochrome P450 (CYP) isozymes in the liver, lung, kidney, intestine, brain, and testis have been reported based on Western blot analysis, Northern blot analysis, and various enzyme activities. Changes in phase II enzyme activities have been reported also. Hence, in this review, changes in the pharmacokinetics of drugs that were mainly conjugated and metabolized via CYPs or phase II isozymes in rats with DMIA or DMIS, as reported in various literature, have been explained. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized in the kidney, and that were excreted mainly via the kidney or bile in DMIA or DMIS rats were reviewed also. For drugs mainly metabolized via hepatic CYP isozymes, the changes in the total area under the plasma concentration–time curve from time zero to time infinity (AUC) of metabolites, AUC_metabolite/AUC_{parent drug} ratios, or the time‐averaged nonrenal and total body clearances (CL_NR and CL, respectively) of parent drugs as reported in the literature have been compared. Key findings After intravenous administration of drugs that were mainly metabolized via hepatic CYP isozymes, their hepatic clearances were found to be dependent on the in‐vitro hepatic intrinsic clearance (CL_int) for the disappearance of the parent drug (or in the formation of the metabolite), the free fractions of the drugs in the plasma, or the hepatic blood flow rate depending on their hepatic extraction ratios. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized via the kidney in DMIA or DMIS rats were dependent on the drugs. However, the biliary or renal CL values of drugs that were mainly excreted via the kidney or bile in DMIA or DMIS rats were faster. Summary Pharmacokinetic studies of drugs in patients with type I diabetes mellitus were scarce. Moreover, similar and different results for drug pharmacokinetics were obtained between diabetic rats and patients with type I diabetes mellitus. Thus, present experimental rat data should be extrapolated carefully in humans.     

胰岛素不同给药途径对糖尿病小鼠葡萄糖代谢的影响

目的：观察胰岛素治疗对糖尿病小鼠口服葡萄糖代谢的影响。方法：四氧嘧啶诱导小鼠糖尿病模型。糖尿病小鼠[^14C]-葡萄糖灌胃，同时腹腔或皮下注射胰岛素。每隔一定时间取尾静脉血测血糖和放射性，2h后处死小鼠，取心、肝、肾组织测放射性。结果：糖尿病小鼠口服[^14C]-葡萄糖后血糖迅速上升，但其血液放射性水平与正常小鼠和胰岛素给药小鼠无差异。糖尿病小鼠皮下注射胰岛素50％出现低血糖。口服[^14C]-葡萄糖后2h，糖尿病小鼠肝、肾放射性水平分别是正常小鼠的4倍和1．5倍，心脏放射性水平降低为正常小鼠的30％。腹腔注射胰岛素的糖尿病小鼠肝、肾和心脏的放射性水平与正常小鼠无统计学差异。皮下注射胰岛素使50％小鼠血糖降至正常，但其肝、肾的放射性水平仍显著高于正常小鼠。对于因皮下注射胰岛素而处于严重低血糖的糖尿病小鼠，肝、肾的放射性水平与正常小鼠无统计学差异，心脏的放射性水平仍显著低于正常小鼠。结论：皮下胰岛素给药可以纠正血糖．但不能纠正糖代谢异常。     

四氧嘧啶诱导兔1型糖尿病模型的实验研究

目的应用不同剂量四氧嘧啶（ALX）诱导兔糖尿病模型,探索一种安全、稳定的糖尿病模型建立方法。方法健康新西兰兔随机分为A、B 2组。2组给ALX前均禁食12 h,A组按150 mg/kg体重1次给药;B组为2次给药法组,第1次按80 mg/kg体重,24 h后按120 mg/kg体重给药。14 d后经耳缘静脉测空腹血糖值,以空腹血糖〉16 mmol/L作为造模成功的标准。比较2组的病死率和成模率。结果A组病死率70%,成模率20%;B组病死率10%,成模率80%。两种不同的给药方法病死率和成模率比较差异均有统计学意义（P〈0.05）。结论应用ALX制备糖尿病模型,是一种经济、安全、可靠的方法,连续2次小剂量给药法优于1次性高剂量给药,降低了病死率,提高了成模率。     

蛋氨酸合成酶还原酶研究新进展

蛋氨酸合成酶还原酶是蛋氨酸合成酶所必需的黄素蛋白. 该基因大小约为34 kb,包含15个外显子. 蛋氨酸合成酶还原酶催化甲基钴胺再生,是蛋氨酸合成酶的辅助因子,对于维持同型半胱氨酸在无毒性水平有重要作用,高浓度半胱氨酸已被确定为独立的心血管疾病的危险因子.