CN113615837B - 一种延缓衰老的核苷酸益生菌胶囊 - Google Patents
一种延缓衰老的核苷酸益生菌胶囊 Download PDFInfo
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Abstract
本发明公开一种延缓衰老的核苷酸益生菌胶囊，属于医药保健技术领域，本发明的核苷酸益生菌胶囊包括胶囊壳和内容物，内容物组分包括4种外源核苷酸和5种益生菌，外源核苷酸包括5’单磷酸胞苷(5’‑CMP)、5’单磷酸腺苷(5’‑AMP)、5’尿苷酸二钠(5’‑UMPNa2)和5’鸟苷酸二钠(5’‑GMPNa2)，益生菌包括嗜酸乳杆菌、植物乳杆菌、干酪乳杆菌等益生菌，益生菌含量均大于1×107CFU/g。本发明的延缓衰老的核苷酸益生菌胶囊，能够清除体内自由基，抑制自由基对机体的氧化损伤，延长细胞寿命，具有延缓衰老、延年益寿、提高免疫力、调节肠道菌群等多种保健功效，并且携带服用方便，是适合中老年人的保健食品。
Description
技术领域
本发明属于医药保健技术领域，具体涉及一种延缓衰老的核苷酸益生菌胶囊。
背景技术
衰老是指人类在发育成熟以后，随时间的增加，机体出现组织结构变化，机能衰退、适应性和抵抗力减退，趋于死亡的过程。衰老作为复杂生命现象的一种变化，是自发的必然的过程。随着人们生活水平的提高，中国即将步入老龄化社会，延缓衰老、健康长寿是很多人尤其是女性追求的目标。追求延年益寿是人类几千年的梦想。如今，预防和延缓衰老已成为当前研究的热点。研究发现，衰老是多种因素综合作用的结果，与遗传基因、自由基、免疫功能紊乱等因素有关。虽然衰老是每个人生命活动中不可抗拒的自然规律，但是采用良好的保健措施，服用延缓衰老的产品，可有效地延缓衰老，推迟生老病死的时间，提高生活质量，让人类在现有的条件下实现最大极限的长寿。
核苷酸是细胞的重要组成成分，是DNA和RNA的前体，在细胞代谢、蛋白质合成和细胞分裂等过程中起着重要的作用。核苷酸在一些特定条件下，如疾病、快速生长发育、营养摄入受限以及内源性合成和表达受阻时，核苷酸成为机体的“必需营养素”。因此，核苷酸可作为实现延缓衰老、益寿延年的潜在物质。
机体衰老的同时会伴随多种慢性疾病的产生，而这些慢性疾病很多都与肠道菌群失调相关。因此，肠道菌群也是影响机体衰老的一个重要指标。益生菌是通过定殖在人体内，对人体健康有重要作用的活性微生物。研究发现，益生菌在调节肠道菌群平衡、促进营养吸收、保持肠道健康等方面具有重要的功效。
目前市场上现有的用于延缓衰老的产品很多，但是这些产品作用低微，见效迟缓，效果较差。因此，研究开发一种成分安全有效，无毒副作用、能够高效延缓机体老化的产品成为当前亟待研究的重要课题。
发明内容
本发明针对上述问题，本发明提供一种延缓衰老的核苷酸益生菌胶囊，其包含4种外源核苷酸和5种益生菌，成分安全有效，无毒副作用，具有增强免疫力、延缓机体老化、增强细胞生命力的功效。
本发明为实现上述目的，通过以下技术方案实现：
一种延缓衰老的核苷酸益生菌胶囊，包括椭圆形胶囊和内容物，所述内容物包括4种外源5’核苷酸或者其钠盐形式的混合物和5种益生菌，重量配比为：5’核苷酸混合物45～75份，益生菌20～30份。
优选的是，所述内容物中4种外源5’核苷酸的重量百分比分别为：CMP 15～45％、AMP15～55％、UMP 6～30％、GMP 14～35％。
优选的是，所述内容物益生菌中各菌种质量百分比为：嗜酸乳杆菌17～32％、植物乳杆菌17～32％、干酪乳杆菌17～32％、瑞士乳杆菌10～23％、戊糖片球菌7～19％。
优选的是，所述内容物的重量配比为：5’单磷酸胞苷(5’-CMP)10～20份，5’单磷酸腺苷(5’-AMP)20～30份，5’尿苷酸二钠(5’-UMPNa2)5～10份，5’鸟苷酸二钠(5’-GMPNa2)10～15份，嗜酸乳杆菌5～7份，植物乳杆菌5～7份，干酪乳杆菌5～7份，瑞士乳杆菌3～5份，戊糖片球菌2～4份。
优选的是，5’单磷酸胞苷10份，5’单磷酸腺苷20份，5’尿苷酸二钠5份，5’鸟苷酸二钠10份，嗜酸乳杆菌5份，植物乳杆菌5份，干酪乳杆菌5份，瑞士乳杆菌3份，戊糖片球菌2份。
优选的是，5’单磷酸胞苷15份，5’单磷酸腺苷25份，5’尿苷酸二钠8份，5’鸟苷酸二钠10份，嗜酸乳杆菌6份，植物乳杆菌6份，干酪乳杆菌6份，瑞士乳杆菌4份，戊糖片球菌3份。
优选的是，5’单磷酸胞苷20份，5’单磷酸腺苷30份，5’尿苷酸二钠10份，5’鸟苷酸二钠15份，嗜酸乳杆菌7份，植物乳杆菌7份，干酪乳杆菌7份，瑞士乳杆菌5份，戊糖片球菌4份。
优选的是，所述益生菌每种菌种的活菌含量均大于1×107CFU/g。
优选的是，胶囊的壁材为麦芽糊精和大豆分离蛋白。
优选的是，所述麦芽糊精和大豆分离蛋白的重量比为1:1～1:2。。
优选的是，所述麦芽糊精和大豆分离蛋白的重量比为1:1.5～1:2。
优选的是，所述核苷酸包括天然核苷酸和人工合成核苷酸。
优选的是，所述益生菌为益生菌活菌冻干粉。
本发明另一方面提供上述核苷酸益生菌胶囊的制备方法，按配比称量上述内容物，混合均匀，获得混合粉，将混合粉装入空心胶囊中，即得核苷酸益生菌胶囊。
本发明另一方面提供上述核苷酸益生菌胶囊在制备延缓衰老的保健食品和/或药品中的应用。
本发明相对于现有技术具有的有益效果如下：
1.本发明是以膳食核苷酸和益生菌为原料，成分安全有效，无毒副作用，二者配合服用，协同作用，能够清除体内自由基，抑制自由基对机体的氧化损伤，延长细胞寿命，具有延缓衰老、延年益寿、提高免疫力、调节肠道菌群等多种保健功效，并且携带服用方便，是适合中老年人的保健食品。
2.本发明的核苷酸益生菌胶囊的制备工序简单易操作，稳定性好，长期服用有益于身体健康。
具体实施方式
下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述的实施例范围之中。下述实施例中，如无特殊说明，所使用的实验方法均为常规方法，所用材料、试剂等均可从生物或化学公司购买。
本发明的延缓衰老的核苷酸益生菌胶囊，包括椭圆形胶囊皮和内容物，胶囊皮的成分包括麦芽糊精和大豆分离蛋白；内容物包含4种膳食核苷酸和多种益生菌。
实施例1
一种延缓衰老的核苷酸益生菌胶囊，包括椭圆形胶囊皮和内容物，胶囊壁材为麦芽糊精、大豆分离蛋白，二者重量比为1:1，内容物组分包括4种5’单核苷酸或者其钠盐形式的混合物和5种益生菌活菌冻干粉，按重量份配比为：5’单磷酸胞苷10份，5’单磷酸腺苷20份，5’尿苷酸二钠5份，5’鸟苷酸二钠10份，嗜酸乳杆菌5份，植物乳杆菌5份，干酪乳杆菌5份，瑞士乳杆菌3份，戊糖片球菌2份。具体制备方法为将上述内容物按配比混合均匀，获得混合粉，将混合粉装入空心胶囊中，每粒胶囊装入0.2g，即得核苷酸益生菌胶囊成品。
实施例2
一种延缓衰老的核苷酸益生菌胶囊，包括椭圆形胶囊皮和内容物，胶囊壁材为麦芽糊精、大豆分离蛋白，二者重量比为1:1.5，内容物组分包括4种5’单核苷酸或者其钠盐形式的混合物和5种益生菌活菌冻干粉，按重量份配比为：5’单磷酸胞苷15份，5’单磷酸腺苷25份，5’尿苷酸二钠8份，5’鸟苷酸二钠10份，嗜酸乳杆菌6份，植物乳杆菌6份，干酪乳杆菌6份，瑞士乳杆菌4份，戊糖片球菌3份。具体制备方法为将上述内容物按配比混合均匀，获得混合粉，将混合粉装入空心胶囊中，每粒胶囊装入0.2g，即得核苷酸益生菌胶囊成品。
实施例3
一种延缓衰老的核苷酸益生菌胶囊，包括椭圆形胶囊皮和内容物，胶囊壁材为麦芽糊精、大豆分离蛋白，二者重量比为1:2，内容物组分包括4种5’单核苷酸或者其钠盐形式的混合物和5种益生菌活菌冻干粉，按重量份配比为：5’单磷酸胞苷20份，5’单磷酸腺苷30份，5’尿苷酸二钠10份，5’鸟苷酸二钠15份，嗜酸乳杆菌7份，植物乳杆菌7份，干酪乳杆菌7份，瑞士乳杆菌5份，戊糖片球菌4份。具体制备方法为将上述内容物按配比混合均匀，获得混合粉，将混合粉装入空心胶囊中，每粒胶囊装入0.2g，即得核苷酸益生菌胶囊成品。
实施例4
为了验证本发明的核苷酸益生菌胶囊对延缓衰老的作用，本实验首先通过考察复配核苷酸的抗氧化性能。
按照实施例1中的核苷酸益生菌胶囊中核苷酸的配比配制5’单磷酸胞苷：5’单磷酸腺苷：5’尿苷酸二钠：5’鸟苷酸二钠重量比为10：20：5：10的混合核苷酸，取0.1g溶于100mL去离子水，制的混合核苷酸母液，进行DPPH自由基清除率的测定和ABTS自由基清除率的测定。
1.DPPH自由基清除率的测定：
将母液分别稀释100，50，25，10，1倍制备成浓度为10μg/mL，20μg/mL，40μg/mL，100μg/mL，500μg/mL的梯度稀释液。
分别取上述浓度150μL样品和150μL浓度为60mg/L的DPPH溶液(无水乙醇稀释)置于96孔板中，混合均匀，30℃避光保存，30min后使用酶标仪测量519nm下吸光度值。DPPH自由基清除率公式如下：
式中，A空白为150μL去离子水和150μL DPPH溶液的吸光度，A样品为150μL样品和150μL DPPH溶液的吸光度；IC50为DPPH自由基清除率达到50％时样品的浓度。
2.ABTS自由基清除率的测定：
(1)将母液分别稀释100，50，25，10，1倍制备成浓度为10μg/mL，20μg/mL，40μg/mL，100μg/mL，500μg/mL的梯度稀释液。
(2)将7mmol/L的ABTS溶液和140mmol/L的过硫酸钾溶液以62.5：1的比例混合，室温避光静置过夜，形成ABTS储备液，使用前用去离子水稀释成5mmol/L的ABTS工作液。
(3)分别取0.15mL上述稀释液样品与2.85mL ABTS工作液混合，30℃下静置8min，以去离子水为空白在734nm下测定吸光度。
ABTS自由基清除率公式如下：
式中，A空白为0.15mL去离子水和2.85mL ABTS工作液的吸光度，A样品为0.15mL样品和2.85mL ABTS工作液的吸光度。IC50为ABTS自由基清除率达到50％时样品的浓度。
参考上述同样的检测方法检测实施例2中的核苷酸益生菌胶囊中核苷酸的配比配制5’单磷酸胞苷：5’单磷酸腺苷：5’尿苷酸二钠：5’鸟苷酸二钠重量比为15：25：8：10的混合核苷酸以及实施例3中的核苷酸益生菌胶囊中核苷酸的配比配制5’单磷酸胞苷：5’单磷酸腺苷：5’尿苷酸二钠：5’鸟苷酸二钠重量比为20：30：10：15的混合核苷酸的抗氧化性能，同时以配制5’单磷酸胞苷：5’单磷酸腺苷：5’尿苷酸二钠：5’鸟苷酸二钠重量比为1：1：1：1的混合核苷酸作为对照实验，实验数据以均值±标准偏差表示，实验结果如表1所示。
表1.混合核苷酸的抗氧化性能
结果表明，与对照组相比，实施例1-3的核苷酸混合物均具有较高的抗氧化性能，能够更有效的清除机体的自由基，从而高效延缓机体的老化和增强细胞生命力。
实施例5
机体代谢会产生大量的氧化物自由基，破坏细胞功能，导致器官老化，从而导致机体的衰老。超氧化物歧化酶(SOD)可以清除对机体有害的超氧阴离子自由基。谷胱甘肽过氧化物酶(GSH-Px)是机体内广泛存在的一种重要的过氧化物分解酶。可以使有毒的过氧化物还原成无毒的羟基化合物，从而保护细胞膜的结构及功能不受过氧化物的干扰及损害。因此，SOD和GSH-Px活性可以反映出组织的抗氧化能力，是评价机体衰老的重要指标。MDA是脂质的过氧化产物，与机体内自由基的产生情况和机体组织细胞的脂质过氧化程度密切相关，可反映出机体组织的氧化应激的损伤状态，也作为评价衰老的重要指标之一。为进一步地验证本发明的核苷酸益生菌胶囊对延缓衰老的作用，对实施例1～3中制备的的核苷酸益生菌胶囊进行动物实验，本发明采用快速老化倾向SAMP-8小鼠，测试本发明核苷酸益生菌胶囊对小鼠衰老的延缓作用。
首先以实施例1中制备的核苷酸益生菌胶囊为例进行实验，取40只快速老化倾向小鼠(SAMP-8小鼠，购自北京维通利华实验动物技术有限公司)，体重为(20±5)g，随机分成4组，即空白组(胶囊中仅含有基础饲料)、对照组1(胶囊中仅含有与实施例1的核苷酸益生菌胶囊相同量及相同配比的核苷酸)、对照组2(胶囊中仅含有与实施例1的核苷酸益生菌胶囊相同量及相同配比的益生菌)、试验组(实施例1的核苷酸益生菌胶囊)，每组10只，以美国营养学会(American Institute of Nutrition，AIN-93G)动物饲料作为基础饲料，适应性喂养一周，试验分别饲喂空白组、对照组和试验组对应的胶囊，每只SAMP-8小鼠每次2粒，每天3次，连续给药30天，每天记录小鼠状态。
根据结果可知，空白组和对照组1-2随着时间延长，小鼠出现精神状态不佳、活动缓慢的情况，出现衰老迹象，而饲喂本发明的核苷酸益生菌胶囊的试验组小鼠精神和健康状况良好。
考察末次给药后，眼底取血，室温静置待血液完全凝固后离心分离血清备用，随后脱臼发处死小鼠，迅速分离肝脏，氯化钠溶液冲洗干净后制备10％组织匀浆，离心，分离的组织匀浆上清液备用。
小鼠血清及肝组织的SOD和GSH-Px活性按照超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的测定参照试剂盒的说明书进行测定，小鼠血清及肝组织的脂质的过氧化物丙二醛(MDA)含量通过硫代巴比妥酸分光法进行测定。实验数据以均值±标准偏差表示，实验结果如表2-4所示。
表2.饲喂实施例1的胶囊后小鼠体内MDA、SOD和GSH-Px含量数据
表3.饲喂实施例2的胶囊后小鼠体内MDA、SOD和GSH-Px含量数据
表4.饲喂实施例3的胶囊后小鼠体内MDA、SOD和GSH-Px含量数据
结果表明，与空白对照组相比，对照组1-2小鼠血清及肝组织中的SOD活性、GSH-Px活性的活性有所提高，小鼠血清及肝组织中MDA含量有所降低；试验组各指标数值明显优于对照组1-2，进一步表明本发明的抗衰老核苷酸益生菌胶囊可协同增强机体清除自由基的能力，减少组织细胞损伤的程度，显著延缓机体衰老的作用，且没有不良反应。
实施例6
试验方法：在同一地区，同一时间邀请500例皮肤出现老化的女性志愿者，年龄45-60岁，平均年龄54岁。
入选标准：皮肤有轻度或中度的皱纹、皮肤干燥，弹性降低，色素沉着、肤色灰暗等现象；并随机分为10组，每组50人，10组志愿者分别对应空白组(胶囊中仅含有等量的葡萄糖)、对照组1(胶囊中仅含有与实施例1的核苷酸益生菌胶囊相同量及相同配比的核苷酸)、对照组2(胶囊中仅含有与实施例1的核苷酸益生菌胶囊相同量及相同配比的益生菌)、对照组3(胶囊中仅含有与实施例2的核苷酸益生菌胶囊相同量及相同配比的核苷酸)、对照组4(胶囊中仅含有与实施例2的核苷酸益生菌胶囊相同量及相同配比的益生菌)、对照组5(胶囊中仅含有与实施例3的核苷酸益生菌胶囊相同量及相同配比的核苷酸)、对照组6(胶囊中仅含有与实施例3的核苷酸益生菌胶囊相同量及相同配比的益生菌)、试验组1(实施例1的核苷酸益生菌胶囊)、试验组2(实施例2的核苷酸益生菌胶囊)、试验组3(实施例3的核苷酸益生菌胶囊)，且每组志愿者均使用对应试验产品作为唯一抗衰老和抗氧化产品，每人每天服用2粒，每日3次，为期四周，试验结束后参加试验的志愿者反馈皮肤变化情况和使用感受，效果评价结果如表5所示。
表5.不同组胶囊产品的效果评价结果
| 组别 | 每组参与人数 | 面部皮肤紧凑 | 精力充沛 | 记忆力改善 | 睡眠质量改善 |
| 试验组1 | 50 | 46 | 45 | 40 | 42 |
| 试验组2 | 50 | 45 | 50 | 41 | 46 |
| 试验组3 | 50 | 49 | 47 | 43 | 47 |
| 对照组1 | 50 | 34 | 30 | 32 | 33 |
| 对照组2 | 50 | 15 | 20 | 18 | 21 |
| 对照组3 | 50 | 37 | 34 | 30 | 38 |
| 对照组4 | 50 | 20 | 23 | 25 | 22 |
| 对照组5 | 50 | 39 | 35 | 37 | 36 |
| 对照组6 | 50 | 25 | 24 | 26 | 25 |
| 空白组 | 50 | 7 | 13 | 10 | 8 |
上述结果表明，与空白组和对照组1-6相比，本发明核苷酸益生菌胶囊能够更为有效地改善面部皮肤、精力、记忆力以及睡眠质量，从而达到延缓衰老的目的。
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)
1.一种延缓衰老的核苷酸益生菌胶囊，其特征在于，包括胶囊和内容物，所述内容物包括4种外源核苷酸或者其钠盐形式的混合物和5种益生菌，重量配比为：核苷酸或者其钠盐形式的混合物45～75份，益生菌20～30份；
所述内容物的重量配比为：5’单磷酸胞苷(5’-CMP)10～20份，5’单磷酸腺苷(5’-AMP)20～30份，5’尿苷酸二钠(5’-UMPNa2)5～10份，5’鸟苷酸二钠(5’-GMPNa2)10～15份，嗜酸乳杆菌5-7份，植物乳杆菌5～7份，干酪乳杆菌5～7份，瑞士乳杆菌3～5份，戊糖片球菌2～4份。
2.根据权利要求1所述的核苷酸益生菌胶囊，其特征在于，所述内容物的重量配比为：
5’单磷酸胞苷10份，5’单磷酸腺苷20份，5’尿苷酸二钠5份，5’鸟苷酸二钠10份，嗜酸乳杆菌5份，植物乳杆菌5份，干酪乳杆菌5份，瑞士乳杆菌3份，戊糖片球菌2份；
或者，所述内容物的重量配比为：
5’单磷酸胞苷15份，5’单磷酸腺苷25份，5’尿苷酸二钠8份，5’鸟苷酸二钠10份，嗜酸乳杆菌6份，植物乳杆菌6份，干酪乳杆菌6份，瑞士乳杆菌4份，戊糖片球菌3份；
或者，所述内容物的重量配比为：
5’单磷酸胞苷20份，5’单磷酸腺苷30份，5’尿苷酸二钠10份，5’鸟苷酸二钠15份，嗜酸乳杆菌7份，植物乳杆菌7份，干酪乳杆菌7份，瑞士乳杆菌5份，戊糖片球菌4份。
3.根据权利要求1所述的核苷酸益生菌胶囊，其特征在于，所述益生菌中每种菌种的活菌含量均大于1×107CFU/g。
4.根据权利要求1所述的核苷酸益生菌胶囊，其特征在于，所述胶囊的壁材为麦芽糊精和大豆分离蛋白，所述麦芽糊精和大豆分离蛋白的重量比为1:1～1:2。
5.根据权利要求4所述的核苷酸益生菌胶囊，其特征在于，所述麦芽糊精和大豆分离蛋白的重量比为1:1.5～1:2。
6.权利要求1-5任一项所述的核苷酸益生菌胶囊的制备方法，其特征在于，按配比称量核苷酸和益生菌，混合均匀，获得混合粉，将混合粉装入空心胶囊中，即得核苷酸益生菌胶囊。
7.权利要求1-5任一项所述的核苷酸益生菌胶囊在制备延缓衰老的保健食品和/或药品中的应用。
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