模拟胰岛素的高分子聚n-乙烯基吡咯烷酮基钒金属配合物。第2部分。钒大分子金属配合物降血糖活性的评价

Veronika A. Mukhina, V. Prikhodko, N. Kirillova, N. Anisimova, A. Ivanov
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摘要

本文报道了一种以聚n -乙烯基吡咯烷酮为基础的新型氧化钒金属聚合物配合物的合成方法,用波谱法研究了其结构,并确定了其组成。电子谱和振动谱数据表明,该配合物是由金属与聚合物内酰胺环的氮原子和氧原子相互作用形成的,需要注意的是,这种相互作用可以通过分子内配位或分子间配位发生。采用Prozorovsky表达法估计急性口服毒性,测定了合成配合物的LD50中位数为1350±160 mg/kg。所得LD50值使该金属-聚合物配合物属于低毒物质,为其进一步的拟胰岛素活性研究开辟了前景。本研究的目的是研究基于聚n -乙烯基吡咯烷酮(PVP)的新型钒基(VO2+)聚合物衍生物的降血糖活性,并探讨这些化合物或基于它们的组合物用于预防和治疗2型糖尿病的可能性。这项工作描述了一种在动物身上建立2型糖尿病实验模型的方法,该方法结合了高脂肪饮食和链脲佐菌素作为致糖尿病剂的使用。评价所研究的金属-聚合物配合物对实验动物血糖、尿等碳水化合物代谢指标的影响,以及治疗期间动物日利尿变化的结果。本文给出了金属聚合物配合物对实验动物碳水化合物代谢指标的影响,如治疗期间和治疗后动物的血、尿葡萄糖变化、每日利尿变化等。以二甲双胍为对照,考察了所制钒化合物对碳水化合物指标的影响。发现新型钒金属聚合物配合物具有降血糖活性,可使高脂饮食/链脲佐菌素诱导的糖尿病实验动物血糖水平恢复正常。
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Insulin-mimetic macromolecular poly-N-vinylpyrrolidone-based vanadium metallocomplexes. Part 2. Assessment of the hypoglycemic activity of the vanadium macromolecular metal complex
In a previous work, a method for the synthesis of a new metal-polymer complex of oxovanadium (IV) based on poly-N-vinylpyrrolidone was described, its structure was studied by spectral methods, and its composition was determined. Based on the data of electronic and vibrational spectroscopy, it was shown that the complex is formed due to the interaction of the metal with nitrogen and oxygen atoms of the polymer lactam ring, it should be noted that this type of interaction can occur both by intramolecular or intermolecular coordination. Using the Prozorovsky’s express method for estimation of acute oral toxicity the median value of LD50 of the synthesized complex was determined and it amounted to 1350 ± 160 mg/kg. The obtained LD50 value allow to attribute this metal-polymer complex to the class of low-toxic substances, which opens up some prospects for its further research on insulinomimetic activity. The aim of this work is to investigate the hypoglycemic activity of new polymer derivatives of vanadyl (VO2+) based on poly-N-vinylpyrrolidone (PVP) and to explore the possibility of using these compounds or compositions based on them for the prevention and treatment of type 2 diabetes. The work describes a method for creating an experimental model of type 2 diabetes mellitus in animals, combining the use of a high-fat diet and streptozotocin as a diabetogenic agent. The results of evaluating the effect of the studied metal-polymer complexes on such indicators of carbohydrate metabolism of laboratory animals as changes in blood glucose and urine, change daily diuresis of animals during treatment. The results of evaluating the effect of the metal-polymer complexes on such indicators of carbohydrate metabolism in laboratory animals as a change in blood and urine glucose, a change in the daily diuresis of animals during and after treatment are presented. The investigation of the effect of the obtained vanadium compounds on carbohydrate indices was carried out using metformin as a comparison drug. It was found that the new metal-polymer complexes of vanadium have hypoglycemic activity, normalizing the blood glucose level of laboratory animals with high-fat diet/ streptozotocin induced diabetes.
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