CN113662960A - 一种硒化葡甘寡糖在预防和治疗糖尿病中的应用 - Google Patents
一种硒化葡甘寡糖在预防和治疗糖尿病中的应用 Download PDFInfo
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- CN113662960A CN113662960A CN202010404332.1A CN202010404332A CN113662960A CN 113662960 A CN113662960 A CN 113662960A CN 202010404332 A CN202010404332 A CN 202010404332A CN 113662960 A CN113662960 A CN 113662960A
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- selenized
- glucomannan
- oligosaccharide
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- glucose
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Abstract
本发明涉及硒化寡糖技术领域，具体是硒化葡甘寡糖的新应用。硒化葡甘寡糖为葡甘寡糖***酯，可应用于预防和/或治疗糖尿病药物中，也可应用于降血糖药物或降血糖食品中。硒化葡甘寡糖的糖链是β‑D‑葡萄糖和β‑D‑甘露糖通过β‑1,4‑糖苷键为主链，部分β‑1,3‑葡萄糖为支链的寡糖，硒含量为50mg/kg～20g/kg。硒化葡甘寡糖具有较好的降血糖活性，效果优于葡甘寡糖和无机硒***，且原料来源于天然多糖，安全无副作用。
Description
技术领域
本发明涉及硒化寡糖技术领域，具体是硒化葡甘寡糖的新应用。
背景技术
糖尿病是一种严重危害人体健康的常见慢性终身疾病，具体表现为血液葡萄糖浓度升高，从而危害其它脏器，包括肾、眼睛和心血管等。目前糖尿病的预防和治疗主要依赖西药，但是长期使用会有严重的副作用。胰岛素是较有效的控制糖尿病的生物药物，但是目前的用药比较麻烦。全世界的糖尿病及隐性糖尿病超过10％，亟需开发安全有效、使用方便的食品或者药物。
寡糖是一类具有多种生物活性的天然生物分子。魔芋等来源的葡甘寡糖(Konjacoligo-glucomannan,KOGM)，其分子量小，在水中可溶，易于吸收，具有多种生物活性，与魔芋多糖相比，魔芋低聚糖具有优良的性能，具有改善食品品质，保鲜食品，改善人体肠道菌群，增强免疫力，调节血糖、血脂以及肠道解毒等功能。硒是生命必需的微量元素，具有抗衰老、抗肿瘤、调节机体免疫力、影响人和动物的生殖发育、解毒等生物学功能。硒在体内以硒代半胱氨酸的形式构成谷胱甘肽过氧化物酶的活性中心，可清除自由基，抑制脂氧化或过氧化，并能引起过氧化物的广泛分解或还原，防止细胞损伤。而自由基引发脂质过氧化产生脂质过氧化物，是损害机体的最主要途径之一。某些癌症、肿瘤、心血管疾病、克山病、大骨节病和艾滋病等都与体内缺硒有关。硒元素不能在体内自行合成，只能靠外部摄入补充。硒主要以有无机硒和有机硒两种形式存在，与无机硒相比，有机硒毒性低、副作用小，活性更好，目前市场上的产品主要含有***类为主。有机硒主要包括硒多糖、硒氨基酸、硒蛋白和硒核酸等，其中硒多糖不但具有无机硒的多种活性，还具有多糖的各种生理功能，并且硒多糖的活性普遍高于硒和多糖,也更利于被机体吸收利用。硒化葡甘寡糖具有很多优异的生理活性，如抗肿瘤活性、抗炎活性等，而硒化葡甘寡糖在降血糖方面的活性还未见报道。
发明内容
本发明的目的是提供硒化葡甘寡糖的一种新的应用。
本发明提供了一种硒化葡甘寡糖在预防和/或治疗糖尿病药物中的应用。
本发明还提供了一种硒化葡甘寡糖在降血糖药物或降血糖食品中的应用。
上述技术方案中，所述硒化葡甘寡糖的结构式如下：
进一步地，所述的硒化葡甘寡糖的糖链是β-D-葡萄糖和β-D-甘露糖通过β-1,4-糖苷键为主链，部分β-1,3-葡萄糖为支链的寡糖；葡萄糖和甘露糖的摩尔比例为4:1～1:4，优选为1:1～1:2；支链与主链的比例为1:2～1:20，优选为1:5～1:10。
进一步地，所述硒化葡甘寡糖的分子量为400～4000Da，优选为400～2000Da；所述硒化葡甘寡糖的聚合度为2～8。
进一步地，所述硒化葡甘寡糖的硒含量为50mg/kg～20g/kg；优选为500mg/kg～5g/kg。
进一步地，所述硒化葡甘寡糖中的寡糖为魔芋葡甘聚糖水解得到。
本发明的有益效果：本发明提供了硒化葡甘寡糖具有较好的降血糖功能，原料来源于天然多糖，安全无副作用。硒化葡甘寡糖使用方法简单，既可用作为普通食品辅助降血糖，也可用于预防、治疗糖尿病的药物中。硒化葡甘寡糖除了具有降血糖功能外，还具有改善肠道菌群、提高免疫、抗氧化等活性，对糖尿病及并发症具有较好效果。
具体实施方式
以下结合具体实施例对本发明作进一步说明，但不以任何方式限制本发明。
实施例1硒化葡甘寡糖的制备
取0.50g聚合度2～8的魔芋降降解得到的葡甘寡糖加入到50mL的0.5％(V/V)的硝酸水溶液中，搅拌溶解；加入0.61g***钠，0.86g氯化钡，搅拌溶解；将上述溶液置于70℃反应9小时；加入0.50g硫酸钠，8000rpm离心去除沉淀；上清液用碳酸氢钠中和至中性；将反应液加入5倍体积乙醇，产生白色沉淀；抽滤得到固体，用乙醇洗2-3遍，将滤饼至于真空干燥器中60℃干燥2小时，得到硒化葡甘寡糖0.4g。
采用ICP-MS分析硒化葡甘寡糖的硒含量为5g/kg。ESI-MS分析硒化葡甘寡糖的聚合度为2～8。
实施例2硒化葡甘寡糖的降血糖活性
1.药物与试剂
魔芋葡甘寡糖：本单位自制，聚合度为2～11，含量99％；实施例1所制备的硒化葡甘寡糖，本单位自制；***钠，97％，天津大茂试剂化学厂；盐酸二甲双胍片：上海施贵宝制药有限公司。
2.设备与仪器
托利多ME2002E/02型电子天平，托利多仪器(上海)有限公司；强生One-Touch稳豪型血糖仪，美国强生公司。
3.动物
7周龄SPF级db/db小鼠88只(雌雄各半)，db/m小鼠8只(雌雄各半)，购自上海斯莱克实验动物有限公司。
4.分组与给药
将db/db小鼠按血糖值随机分为模型对照组、阳性药物(盐酸二甲双胍)组、魔芋葡甘寡糖低、中、高剂量组，***钠低、中、高剂量组和硒化魔芋葡甘寡糖低、中、高剂量组，每组8只。将db/m小鼠8只设为正常对照组。阳性药物组按剂量250mg/kg灌胃给予盐酸二甲双胍，魔芋葡甘寡糖低、中、高剂量组和硒化魔芋葡甘寡糖低、中、高剂量组分别按剂量150、300和600mg/kg灌胃；***钠低、中、高剂量组根据硒化魔芋葡甘寡糖中硒含量折算，分别按剂量1.63、3.26和6.52mg/kg灌胃；模型对照组和正常对照组灌胃给予等体积蒸馏水，灌胃给药容积均为10mL/kg；每日1次，连续灌胃8周。
5.观察指标及检测方法
所有小鼠于给药前、给药8周后称量并记录体质量；所有在给药前、给药4周和8周后，小鼠禁食不禁水10h后，尾部取血，用血糖测定仪进行空腹血糖值的测定。
6.统计学处理
实验数据以“均数±标准差”表示，采用SPSS统计软件进行统计学处理。
7.实验结果
模型动物db/db小鼠是Leptin受体基因缺陷导致的先天肥胖性2型糖尿病小鼠，在出生后2周内就会发生高胰岛素血症，8周后就发展为严重的高血糖症，是研究人类2型糖尿病良好的动物模型。本实验以自发性2型糖尿病db/db小鼠为动物模型。实验结果见表1和表2。
表1是各个处理对小鼠的重量影响的数据。由表1可见，给药前，模型对照组和各给药组db/db小鼠的体质量无明显差异(组间比较，P均＞0.05)，但均显著大于正常对照组db/m小鼠的体质量(P均＜0.01)。给药8周后，魔芋葡甘寡糖组和***钠组均低于模型对照组，但是不明显。硒化魔芋葡甘寡糖中、高剂量组小鼠的体质量显著低于模型对照组(P＜0.05或0.01)。说明硒化魔芋葡甘寡糖对自发性2型糖尿病db/db小鼠重量的控制具有显著作用。
表1各个处理对小鼠体质量的影响(
n＝8)
注：上述数值表示“平均值±标准误”，大写字母表示差异显著性为小于0.01，小写字母表示差异显著性为小于0.05。
表2是各个处理对小鼠的血糖影响的数据。由表2可见，给药前，模型对照组和各给药组db/db小鼠的空腹血糖值均显著高于正常对照组db/m小鼠的血糖值(P均＜0.01)，说明模型可靠。给药4周后，魔芋葡甘寡糖组和***钠组均低于模型对照组，但是不明显。硒化魔芋葡甘寡糖中、高剂量组小鼠的血糖值显著低于模型对照组(P＜0.05或0.01)；给药8周后，魔芋葡甘寡糖组和***钠组均低于模型对照组，但是不明显。硒化魔芋葡甘寡糖低、中、高剂量组小鼠的血糖值显著低于模型对照组(P＜0.01)，与阳性药物组相比，硒化魔芋葡甘寡糖在使用中、高剂量时，其降血糖效果与阳性药物基本一致，甚至优于阳性对照药物；以上结果说明硒化魔芋葡甘寡糖能显著降低自发性2型糖尿病db/db小鼠的血糖。
表2各个处理对小鼠体空腹血糖的影响(
n＝8)
注：上述数值表示“平均值±标准误”，大写字母表示差异显著性为小于0.01，小写字母表示差异显著性为小于0.05。
实验结果显示，魔芋葡甘寡糖和***钠能减轻自发性2型糖尿病db/db小鼠的体质量，降低空腹血糖，但是不明显；硒化魔芋葡甘寡糖能显著减轻自发性2型糖尿病db/db小鼠的体质量，降低空腹血糖，说明硒和魔芋葡甘寡糖衍生的硒化魔芋葡甘寡糖在降低血糖方面具有协同增效作用。本实施例证明硒化葡甘寡糖在糖尿病可以应用于治疗、预防和辅助治疗的药物或食品中。
对于任何熟悉本领域的技术人员而言，在不脱离本发明技术方案范围情况下，都可利用上述揭示的技术内容对本发明技术方案作出许多可能的变动和修饰，或修改为等同变化的等效实施例。因此，凡是未脱离本发明技术方案的内容，依据本发明的技术实质对以上实施例所做的任何简单修改、等同变化及修饰，均应仍属于本发明技术方案保护的范围内。
Claims (7)
1.一种硒化葡甘寡糖在预防和/或治疗糖尿病药物中的应用。
2.一种硒化葡甘寡糖在降血糖药物或降血糖食品中的应用。
3.根据权利要求1或2所述的应用，其特征在于，所述硒化葡甘寡糖的结构式如下：
4.根据权利要求3所述的应用，其特征在于，所述的硒化葡甘寡糖的糖链是β-D-葡萄糖和β-D-甘露糖通过β-1,4-糖苷键为主链，部分β-1,3-葡萄糖为支链的寡糖；葡萄糖和甘露糖的摩尔比例为4:1～1:4，优选为1:1～1:2；支链与主链的比例为1:2～1:20，优选为1:5～1:10。
5.根据权利要求3所述的应用，其特征在于，所述硒化葡甘寡糖的分子量为400～4000Da，优选为400～2000Da；所述硒化葡甘寡糖的聚合度为2～8。
6.根据权利要求1或2所述的应用，其特征在于，所述硒化葡甘寡糖的硒含量为50mg/kg～20g/kg；优选为500mg/kg～5g/kg。
7.根据权利要求1或2所述的应用，其特征在于，所述硒化葡甘寡糖中的寡糖为魔芋葡甘聚糖水解得到。
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