CN111035652B - 钒酸盐酪蛋白复合物在制备降糖药物中的应用 - Google Patents
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Abstract
本发明属于药品或保健品领域，具体提供了一种钒酸盐酪蛋白复合物的单用或与其他药物联用在制备降血糖药物中的应用。钒类化合物对1型和2型糖尿病都有显著地降糖效果，然而在发挥药效的同时常常伴随着较强的毒副作用，表现为肾毒性和肝毒性。酪蛋白是一种常见的运输载体，在转运药物的过程中具有减毒的作用，为糖尿病的临床治疗和研究提供一定的参考和依据。因此，本发明公开的钒酸盐酪蛋白复合物具有成为新型糖尿病治疗药物的潜力和应用前景。
Description
技术领域
本发明属于药品、保健品领域，涉及一种钒酸盐酪蛋白复合物在制备降糖药物中的应用。
背景技术
随着全球经济水平的提高和现代人饮食习惯的改变，全球范围内的糖尿病患者人数逐年升高。目前，糖尿病已经成为危害人类健康问题的巨大难题之一。糖尿病是一组以高血糖为特征的代谢性疾病，主要是由于体内胰岛素的含量过低，分泌受到抑制或者无法与受体结合起作用所导致的。糖尿病的主要病症是血糖高及糖尿，而且还会伴随着多饮多食疲乏无力的状况。并且当血糖长时间处在高水平，会对人体多处组织或脏器造成损伤，主要包括血管、神经、肾脏损伤等。近些年来，中国的糖尿病患者也不断地增多，据统计，平均每10个人就有一个糖尿病患者，糖尿病也越来越成为威胁国人健康的杀手。
糖尿病是一种终身疾病，很难彻底治愈。随着糖尿病机制与糖尿病类药物的作用机制的深入研究，药物的联合应用越来越受重视。药物的联合应用，不仅可以提高疗效，而且可以降低毒副作用的发生率，相对于单独用药具有明显优势。研究表明钒类化合物在人体内具有胰岛素样作用，在I型和II型糖尿病啮齿动物模型中具有使葡萄糖稳态和胰岛素敏感性正常化的能力，以及在一些糖尿病患者中改善胰岛素敏感性的能力，是治疗糖尿病的潜在药物。
酪蛋白是主要从牛奶中提取的一种混合蛋白质，具有高乳化性，稳定性，胶凝性，及生物相容性，已经广泛应用于食品及药物载体领域。因为酪蛋白具有亲水和亲脂的氨基酸残基，所以在溶液中能自发组成胶束，形成可降解的，具有缓释能力的微球。以酪蛋白为载体材料制备的药物传输系统不仅具有生物可降解性，而且具有药物缓释能力，具有良好的研究前景。目前，钒酸盐酪蛋白复合物在制备治疗糖尿病药物中的应用还未见报道。
发明内容
本发明目的是提供一种钒酸盐酪蛋白复合物在制备降糖药物中的应用。本发明对酪蛋白降低钒酸盐毒性机制进行阐述，为开发出一种全新的防治糖尿病药物提供实验依据。
本发明采用的技术方案为：钒酸盐酪蛋白复合物单用或与其他药物联用在制备降糖药物中的应用。
上述的应用，钒酸盐酪蛋白复合物单用或与其他药物联用在制备治疗糖尿病药物中的应用。
优选地，上述的应用，所述的钒酸盐是正钒酸钠。
优选地，上述的应用，所述的钒酸盐酪蛋白复合物中正钒酸钠的浓度为1×10-6-4×10-6mol/L。
优选地，上述的应用，所述的钒酸盐酪蛋白复合物中酪蛋白的浓度为1×10-5mol/L。
优选地，上述的应用，钒酸盐酪蛋白复合物的使用浓度为6.25-25μM。
本发明的有益效果是：
本发明酪蛋白对正钒酸钠具有缓释作用，正钒酸钠与酪蛋白结合后，可以降低钒酸盐的毒性，并且具有良好的促进葡萄糖吸收活性。本发明提供一种钒酸盐酪蛋白复合物在制备降糖药物中的全新应用。结果显示酪蛋白与钒酸盐之间存在稳定的相互作用，且具有良好的促进糖吸收作用。
附图说明
图1是正钒酸钠酪蛋白复合物中，正钒酸钠溶液不同浓度的荧光光谱。
其中：酪蛋白浓度为1×10-5mol/L，a为空白对照组，a～e代表正钒酸钠浓度分别为0、1、2、3、4×10-6mol/L。
图2是正钒酸钠酪蛋白复合物中，正钒酸钠溶液不同浓度的同步荧光光谱Δλ＝15nm。
其中：酪蛋白浓度为1×10-5mol/L，a～e代表正钒酸钠溶液浓度分别为0、1、2、3、4×10-6mol/L。
图3是正钒酸钠酪蛋白复合物中，正钒酸钠溶液不同浓度的同步荧光光谱Δλ＝60nm。
其中：酪蛋白浓度为1×10-5mol/L，a～e代表正钒酸钠溶液浓度分别为0、1、2、3、4×10-6mol/L。
图4是钒酸盐酪蛋白复合物的使用浓度为6.25、12.5、25μM促进HL-7702肝细胞葡萄糖消耗实验结果。
其中：a为空白对照组，b为模型组，c～e为钒酸盐与酪蛋白化合物处理组，浓度分别为6.25、12.5、25μM，f为罗格列酮处理组，使用浓度为10μM，g为酪蛋白处理组，酪蛋白浓度为1×10-5mol/L。
具体实施方式
实施例1钒酸盐与酪蛋白相互作用检测
取1mL浓度为1.0×10-4mol/L酪蛋白溶液和一定浓度的单体化合物正钒酸钠溶液，于10mL容量瓶中，之后用超纯水定容至10mL，酪蛋白溶液的浓度为1.0×10-5mol/L；
调节正钒酸钠溶液的浓度，使正钒酸钠的浓度分别为0、1、2、3、4×10-6mol/L，25℃反应5min；
荧光光谱的测定：分别将样品放入样品池为1.0cm的石英比色皿里，在荧光光谱仪上进行扫描，以150W氙灯为光源，发射波长范围设定在200-500nm，激发波长为280nm，激发及发射狭缝为2.5nm，PMT电压750V，扫描速度为720nm/min；
同步荧光光谱的测定：分别将样品放入样品池为1.0cm的石英比色皿里，在荧光光谱仪上进行扫描，以150W氙灯为光源，扫描模式设置成同步荧光模式Δλ＝15或60nm，发射波长范围设定在200-350nm，激发及发射狭缝为2.5nm，PMT电压750V，扫描速度为720nm/min；
荧光结果：25℃下，酪蛋白与正钒酸钠在不同浓度下的荧光光谱如图1所示，随着正钒酸钠浓度的不断增加酪蛋白发生规律的猝灭现象，说明二者之间存在相互作用，经过计算，正钒酸钠对酪蛋白的猝灭作用属于静态猝灭。
同步荧光结果表明：酪蛋白中主要的荧光基团为色氨酸和酪氨酸残基。设定Δλ为15nm时，同步荧光谱可以反映酪氨酸残基的特征信息；当Δλ为60nm时，同步荧光谱可以反映色氨酸残基的特征信息。如图2和图3所示，随着正钒酸钠浓度的升高，同步荧光谱实验结果表明酪氨酸残基的荧光很弱(Δλ＝15nm)，且色氨酸残基的荧光降低速度(Δλ＝60nm)远快于酪氨酸残基，说明色氨酸残基是正钒酸钠猝灭酪蛋白内源荧光的主要作用位点。酪氨酸残基的同步荧光光谱图峰位位置发生了明显的蓝移，而色氨酸残基的同步荧光光谱图峰位位置发生了明显的红移，这表明正钒酸钠对色氨酸和酪氨酸残基附近微环境也产生影响。本实验说明酪蛋白对正钒酸钠具有良好的结合作用。
实施例2钒酸盐与酪蛋白复合物降糖作用检测
以人正常肝细胞HL-7702建立胰岛素抵抗细胞模型，33.4μM胰岛素和2μM地塞米松处理72h，后使用无血清培养基培养12h检测细胞葡萄糖消耗水平，其中模型组葡萄糖摄取水平仅为空白对照组的40％，证明胰岛素抵抗模型建立成功。
葡萄糖消耗水平测定：采用葡萄糖氧化酶法检测各组细胞的葡萄糖消耗量，实验分为空白对照组，模型组，钒酸盐以及酪蛋白复合物处理组，酪蛋白处理组及罗格列酮处理组。建模成功后，使用PBS轻轻洗涤各组细胞两次，按照分组对应给药，并用无血清培养基培养12h，再检测各组细胞葡萄糖消耗量。
葡萄糖消耗水平测定结果：如图4所示，与空白对照组相比，模型组葡萄糖消耗量下降明显，葡萄糖消耗量仅为对照组的40％，加入不同浓度的钒酸盐与酪蛋白复合物处理后，细胞的葡萄糖消耗量升高显著，葡萄糖消耗量分别为对照组的61％、73％、88％，钒酸盐的使用浓度的越高，葡萄糖消耗量增加越明显，并且单独的酪蛋白处理对细胞的葡萄糖消耗能力没有影响。本实验说明，钒酸盐酪蛋白复合物具有良好的促进葡萄糖吸收作用。
Claims (6)
1.钒酸盐酪蛋白复合物单用或与其他药物联用在制备降糖药物中的应用。
2.如权利要求1所述的应用，其特征在于，钒酸盐酪蛋白复合物单用或与其他药物联用在制备治疗糖尿病药物中的应用。
3.如权利要求1或2所述的应用，其特征在于，所述的钒酸盐是正钒酸钠。
4.如权利要求3所述的应用，其特征在于，所述的钒酸盐酪蛋白复合物中正钒酸钠的浓度为1×10-6-4×10-6mol/L。
5.如权利要求3所述的应用，其特征在于，所述的钒酸盐酪蛋白复合物中酪蛋白的浓度为1×10-5mol/L。
6.如权利要求3所述的应用，其特征在于，钒酸盐酪蛋白复合物的使用浓度为6.25-25μM。
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