CN112546063A - 牛磺酸镁在制备改善认知功能的补充剂中的应用 - Google Patents
牛磺酸镁在制备改善认知功能的补充剂中的应用 Download PDFInfo
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- YZURQOBSFRVSEB-UHFFFAOYSA-L magnesium;2-aminoethanesulfonate Chemical compound [Mg+2].NCCS([O-])(=O)=O.NCCS([O-])(=O)=O YZURQOBSFRVSEB-UHFFFAOYSA-L 0.000 title claims abstract description 41
- 239000013589 supplement Substances 0.000 title claims abstract description 18
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
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- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 5
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- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 description 2
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- 208000008167 Magnesium Deficiency Diseases 0.000 description 1
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/16—Inorganic salts, minerals or trace elements
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/32—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
- C07C303/44—Separation; Purification
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
本发明公开了牛磺酸镁在制备改善认知功能的补充剂中的应用。经过动物实验证明,牛磺酸镁有助于改善整体认知功能和记忆力,还可以改善偏头痛。
Description
技术领域
本发明涉及牛磺酸镁在制备改善认知功能的补充剂中的应用,属于食品技术领域。
背景技术
镁是人体内含量最多的阳离子之一,是人体细胞内占第二位(仅次于钾)的阳离子,镁参与蛋白质的合成,镁能激活体内多种酶,能调节神经肌肉和中枢神经系统的活动,保障心机正常收缩,镁几乎参与人体内所有的新陈代谢。人体缺镁可引起许多疾病,反之,镁可治疗上述相关的疾病。作为补充镁离子的首选药—硫酸镁在临床上应用作为广泛。
牛磺酸是人体所必需的十八种氨基酸之一,是一种化学结构简单的含硫氨基酸,为α-氨基乙磺酸,不参与蛋白质组成和代谢,而是以游离形式存在或与胆汁酸形成复合物。牛磺酸在生物体内参与一系列的生理学过程,如与胆汁酸结合、调节渗透压、外源化合物的解毒、细胞膜的稳定、细胞钙流动调节、神经发育、神经兴奋性调节、神经保护、抗氧化和抗心律失常等,具有广泛的生物活性,对血管、神经、肌肉运动、内分泌、免疫等系统发挥良好的调节作用,特别对婴儿大脑和视觉发育有重要的作用。
发明内容
为了克服现有技术的不足,本发明提供了牛磺酸镁在制备改善认知功能的补充剂中的应用。
本发明是通过以下技术方案来实现的:
牛磺酸镁在制备改善认知功能的补充剂中的应用。
所述牛磺酸镁是通过以下步骤获得的:
(1)将氢氧化镁与水混合后制成混悬液,加热至75-85℃,备用;
(2)将牛磺酸与水混合制成牛磺酸水溶液,保持温度在75-85℃,缓慢加入步骤(1)中75-85℃的混悬液,添加完成后继续加热,回流反应5-10min后过滤,得到滤液;
(3)将滤液浓缩后,向滤液中加入甲醇,搅拌后在0-4℃中静置24h,再次过滤,将过滤后的澄清液浓缩,得到最后的牛磺酸镁。
所述牛磺酸镁是通过以下步骤获得的:
(1)将氢氧化镁1.6g与水30-50ml混合后制成混悬液,加热至75-85℃,备用;
(2)将牛磺酸5g与水100-125ml混合制成牛磺酸水溶液,保持温度在75-85℃,缓慢加入步骤(1)中75-85℃的混悬液,添加完成后继续加热,回流反应5-10min后过滤,得到滤液;
(3)将滤液浓缩后,向滤液中加入甲醇15-20ml,搅拌后在0-4℃中静置24h,再次过滤,将过滤后的澄清液浓缩,得到最后的牛磺酸镁。
所述的牛磺酸镁在制备改善认知功能的补充剂中的应用,所述牛磺酸镁在补充剂中的添加量为10-30%。
牛磺酸在自然海洋生物中含量最高,是一种可以直接从动植物中提取或人工合成的小分子物质,牛磺酸是人体所必需的十八种氨基酸之一,是一种化学结构简单的含硫氨基酸,为α-氨基乙磺酸,不参与蛋白质组成和代谢,而是以游离形式存在或与胆汁酸形成复合物。牛磺酸在生物体内参与一系列的生理学过程,如与胆汁酸结合、调节渗透压、外源化合物的解毒、细胞膜的稳定、细胞钙流动调节、神经发育、神经兴奋性调节、神经保护、抗氧化和抗心律失常等,具有广泛的生物活性,对血管、神经、肌肉运动、内分泌、免疫等系统发挥良好的调节作用,特别对婴儿大脑和视觉发育有重要的作用。
经过动物实验证明,牛磺酸镁有助于改善整体认知功能和记忆力,还可以改善偏头痛,并且效果比单独的硫酸镁或牛磺酸效果要好。将牛磺酸镁应用于营养补充剂中,可以改善使用者的认知功能。
具体实施方式
下面对本发明作进一步描述。以下实施例仅用于更加清楚地说明本发明的技术方案,而不能以此来限制本发明的保护范围。
牛磺酸镁制备方法如下:
(1)将氢氧化镁1.6g与水30-50ml混合后制成混悬液,加热至75-85℃,备用;
(2)将牛磺酸5g与水100-125ml混合制成牛磺酸水溶液,保持温度在75-85℃,缓慢加入步骤(1)中75-85℃的混悬液,添加完成后继续加热,回流反应5-10min后过滤,得到滤液;
(3)将滤液浓缩后,向滤液中加入甲醇15-20ml,搅拌后在0-4℃中静置24h,再次过滤,将过滤后的澄清液浓缩,得到最后的牛磺酸镁。
补充剂的制备方法如下:
将牛磺酸镁与补充剂其它成分混合后得到补充剂,其中牛磺酸镁的添加量占补充剂总重量的10-30%。
一、学习记忆行为学动物试验
1、材料和方法
1.1实验动物
昆明种小鼠,体重24-30g。
1.2牛磺酸镁对小鼠学习记忆行为的影响
动物适应性饲养3d后开始实验分组观察。实验分记忆获得障碍模型和记忆再现障碍模型两批,每批实验用动物90只,将小鼠随机分为模型对照组、牛磺酸组、硫酸镁组、硫酸镁+牛磺酸组、牛磺酸镁低、中、高剂量组、阳性组,每组10只,给药剂量见表1。模型组灌胃给予溶剂0.5%羧甲基纤维素钠溶液作为对照。硫酸镁+牛磺酸组中硫酸镁和牛磺酸的重量比为1:1。
1.2.1记忆获得障碍模型的制备及试验
采用东莨菪碱(3mg/kg)制备记忆获得障碍模型。实验动物按分组情况连续给予相应受试物30d,第30d给予受试物30min后,模型对照组、牛磺酸组、硫酸镁组、硫酸镁+牛磺酸组、牛磺酸镁低、中、高剂量组、阳性组(石杉碱甲)均用东莨菪碱(3mg/kg)进行腹腔注射,10min后开始跳台法训练。第31d给受试物30min后,用跳台法测试记忆成绩。
1.2.2记忆再现障碍模型制备及分组试验
采用40%乙醇(0.1mL/10g)制备记忆再现障碍模型。实验动物按分组情况连续给予相应受试物30d,第30d给予受试药30min后,进行避暗法训练。第31d给受试物30min后,模型对照组、牛磺酸组、硫酸镁组、硫酸镁+牛磺酸组、牛磺酸镁低、中、高剂量组、阳性组(石杉碱甲)均用40%乙醇0.1mL/10g体重的量灌胃,30min后测试记忆成绩。
1.2.3跳台试验将小鼠置于跳台仪中,适应环境5min后,轻放于平台上,当动物从跳台上跳下四肢接触铜栅时,即给予40V交流电压刺激。小鼠正常反应是跳回平台以躲避伤害性刺激。动物可能再次或多次跳下平台,受到电击后又跳回平台。以小鼠跳下平台双足接触铜栅记为错误次数,如此训练5min。24h后进行记忆成绩的测试。将小鼠置平台上,记录其停留在安全平台上的潜伏期(SL)及其3min内受电击的次数(错误次数),若小鼠停留在平台上超过3min,其潜伏期以180s计。
1.2.4避暗试验末次给药后30min训练小鼠,将小鼠面部背向洞口放入明室,启动记时器。动物穿过洞口进入暗室受到电击,记时自动停止。取出小鼠,记录小鼠从放入明室进入暗室遇到电击所需的时间,此即为潜伏期。24h后重作测验,记录每只动物进入暗室的潜伏期和5min的电击次数(5min内未进入暗室者,潜伏期以300s计)。
表1
1.3统计学处理
实验结果均以x±s表示,采用单因素方差分析进行组间显著性比较,样本均数间比较采用t检验。*表示P<0.05,表明给药组与模型组比较有显著性差异;**表示P<0.01,表明给药组与模型组比较有极显著性差异。
2、结果
表2跳台试验结果
由表2可见,与模型组比较,各给药组的小鼠跳台潜伏期均有一定程度的延长,错误次数减少。能够看到同时给药硫酸镁和牛磺酸比单独给药硫酸镁或牛磺酸效果差不多,但是在同等剂量下,牛磺酸镁的效果优于硫酸镁和牛磺酸的效果,也优于硫酸镁+牛磺酸组。
表3避暗试验结果
由表3可见,与模型组比较,各给药组的小鼠避暗潜伏期均有一定程度的延长,错误次数减少。能够看到同时给药硫酸镁和牛磺酸比单独给药硫酸镁或牛磺酸效果差不多,但是在同等剂量下,牛磺酸镁的效果优于硫酸镁和牛磺酸的效果,也优于硫酸镁+牛磺酸组。
二、牛磺酸镁补充剂对硝酸甘油致大鼠偏头痛模型的影响
1、材料和方法
1.1实验动物
Wistar种大鼠,清洁级,体重200-250g。
1.2实验分组
取大鼠72只,雌雄各半,体重200-250g,随机分为八组,模型组、硫酸镁组、牛磺酸组、阳性组、硫酸镁+牛磺酸组、牛磺酸镁高、中、低剂量组,每组动物9只,给药剂量见表4。模型组灌胃给予生理盐水滴鼻。阳性组给予的是盐酸氟桂利嗪胶囊。硫酸镁+牛磺酸组中硫酸镁和牛磺酸的重量比为1:1。
表4
1.3、实验方法
各组动物皮下注射硝酸甘油注射剂10mg/kg,0.22ml/100g,造模后2分钟,各组滴鼻给药1次,给药后连续观察180分钟大鼠的偏头痛反应。
1.4、动物整体体征的观察
从造模开始,30min为一个时段,采用持续时间分段方法,分别记录大鼠每一时段挠头和爬笼的次数,计算总的爬笼次数和总的挠头次数;同时记录大鼠第一次出现挠头的时间和耳红发生率。结果分别见表5和表6。
1.5统计学处理
实验结果均以x±s表示,采用单因素方差分析进行组间显著性比较,样本均数间比较采用t检验。*表示P<0.05,表明给药组与模型组比较有显著性差异;**表示P<0.01,表明给药组与模型组比较有极显著性差异。
2、结果
表5爬笼次数和挠头次数统计
组别 | 爬笼次数 | 挠头次数 |
模型组 | 55.5±6.3 | 68.3±2.8 |
硫酸镁组 | 35.5±3.3* | 47.5±3.6* |
牛磺酸组 | 32.9±3.6* | 41.5±2.4* |
阳性组 | 22.5±2.3* | 25.1±3.1* |
硫酸镁+牛磺酸组 | 30.9±3.9* | 40.2±2.1* |
牛磺酸镁高剂量组 | 24.3±2.8* | 29.5±3.4* |
牛磺酸镁中剂量组 | 33.7±3.7* | 44.5±2.7* |
牛磺酸镁低剂量组 | 48.5±4.3* | 59.2±4.5* |
由表5可见,与模型组比较,各给药组的大鼠爬笼次数和挠头次数均有减少。能够看到同时给药硫酸镁和牛磺酸比单独给药硫酸镁或牛磺酸效果差不多,但是在同等剂量下,牛磺酸镁的效果优于硫酸镁和牛磺酸的效果,也优于硫酸镁+牛磺酸组。
表6爬笼次数和挠头次数统计
组别 | 第一次挠头出现时间(s) | 耳红发生率(%) |
模型组 | 82.5±6.3 | 100 |
硫酸镁组 | 185.5±10.3* | 41 |
牛磺酸组 | 169.4±9.6* | 52 |
阳性组 | 285.5±13.3* | 23 |
硫酸镁+牛磺酸组 | 176.7±11.8* | 48 |
牛磺酸镁高剂量组 | 265.8±10.7* | 30 |
牛磺酸镁中剂量组 | 170.6±12.2* | 48 |
牛磺酸镁低剂量组 | 151.5±9.8* | 53 |
由表6可见,与模型组比较,各给药组的大鼠第一次挠头出现时间较晚,且耳红发生率低。能够看到同时给药硫酸镁和牛磺酸比单独给药硫酸镁或牛磺酸效果差不多,但是在同等剂量下,牛磺酸镁的效果优于硫酸镁和牛磺酸的效果,也优于硫酸镁+牛磺酸组。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明技术原理的前提下,还可以做出若干改进和变形,这些改进和变形也应视为本发明的保护范围。
Claims (4)
1.牛磺酸镁在制备改善认知功能的补充剂中的应用。
2.根据权利要求1所述的一种牛磺酸镁在制备改善认知功能的补充剂中的应用,其特征是,所述牛磺酸镁是通过以下步骤获得的:
(1)将氢氧化镁与水混合后制成混悬液,加热至75-85℃,备用;
(2)将牛磺酸与水混合制成牛磺酸水溶液,保持温度在75-85℃,缓慢加入步骤(1)中75-85℃的混悬液,添加完成后继续加热,回流反应5-10min后过滤,得到滤液;
(3)将滤液浓缩后,向滤液中加入甲醇,搅拌后在0-4℃中静置24h,再次过滤,将过滤后的澄清液浓缩,得到最后的牛磺酸镁。
3.根据权利要求2所述的牛磺酸镁在制备改善认知功能的补充剂中的应用,其特征是,所述牛磺酸镁是通过以下步骤获得的:
(1)将氢氧化镁1.6g与水30-50ml混合后制成混悬液,加热至75-85℃,备用;
(2)将牛磺酸5g与水100-125ml混合制成牛磺酸水溶液,保持温度在75-85℃,缓慢加入步骤(1)中75-85℃的混悬液,添加完成后继续加热,回流反应5-10min后过滤,得到滤液;
(3)将滤液浓缩后,向滤液中加入甲醇15-20ml,搅拌后在0-4℃中静置24h,再次过滤,将过滤后的澄清液浓缩,得到最后的牛磺酸镁。
4.根据权利要求3所述的牛磺酸镁在制备改善认知功能的补充剂中的应用,其特征是,所述牛磺酸镁在补充剂中的添加量为10-30%。
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US20170258828A1 (en) * | 2016-03-08 | 2017-09-14 | Neurocentria, Inc. | Methods of modifying neuronal function by changing intracellular magnesium levels |
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