CN115736261A - 一种生酮饮食组合物及其制备方法和应用 - Google Patents
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Abstract
本发明属于保健食品技术领域，具体提供了一种生酮饮食组合物，以质量百分比计，包括：12±5％乳清蛋白，8‑10％纤维素(BW200)，1‑2％鱼油；0.5‑1％亚麻籽油，1‑2％C8中链脂肪酸油，60‑65％可可脂，1‑2％矿物质(Mineral Mix S10026)，2％磷酸氢钙，1％碳酸钙，2‑3％柠檬酸钾，0.1‑0.2％维生素C(V10001C)0.3‑0.5％酒石酸氢胆碱等。本发明提供的这种生酮饮食组合物适口性好且容易维持，能够缓解自闭症模型小鼠的社交障碍、重复刻板行为等核心症状。该生酮饮食组合物以乳清作为蛋白质来源可提高抗氧化剂谷胱甘肽的含量，提高饮食的耐受性及优化机体蛋白质的来源；组合鱼油和亚麻籽油是抗炎omega‑3脂肪酸的最佳来源；C8MCT油可改善酮体生成。
Description
技术领域
本发明属于保健食品技术领域，具体涉及一种生酮饮食组合物及其制备方法和应用。
背景技术
自闭症是一种复杂的神经发育状态，其特征是社交障碍，兴趣狭窄和重复刻板行为等，通常在儿童0-3岁发病，表现为特征性症状或行为特征。除了这些主要诊断标准中所见的一系列症状外，自闭症患者还表现出各种各样的神经系统合并症，包括智力障碍、癫痫、焦虑和情绪障碍及非神经系统合并症，包括血液高胆固醇血症、免疫失调和胃肠道功能障碍(如，慢性便秘、腹泻、腹痛和胃食管反流)。迄今为止，全球仅有30款药物的在研适应症中包含自闭症，其中有7款药物获批上市，但获批适应症尚不包含自闭症。在美国，仅批准两款药物-利培酮及阿立哌唑用于自闭症治疗，且均不是针对核心症状，特别指出用于降低患者的易怒。截至目前，全球没有一款针对自闭症核心症状的药物上市。因此，本领域仍然需要治疗和减少与自闭症有关的严重程度和症状发生率的改进方法。
生酮饮食是一种高脂中等蛋白低碳水的饮食方案，实质是改为酮体(乙酰乙酸、β-羟基丁酸、丙酮)供能，可通过改变身体能量代谢及肠道菌群互作的方式进而对多种疾病产生特有的效果。经典的生酮饮食是限制性最强的饮食方式，脂肪含量很高、碳水化合物含量很低，最早用于癫痫患者的治疗中，但在干预早期容易引发患者极端情绪、不易耐受且较难坚持。为增加食物的适口性，出现了中链三酰甘油、改良的阿特金斯饮食，低血糖指数治疗等饮食方式。
现有生酮饮食存在以下缺点：
1、经典的生酮饮食限制性最强，通常需住院，且出现不良事件包括嗜睡、严重脱水或酸中毒、情绪变化、炎症、便秘和呕吐等胃肠道问题，被迫中止的原因主要是适口性差、不耐受、难以维持或疗效因个体差异而参差不齐；
2、传统的中链三酰甘油饮食是由中链甘油三酯中提供60％的能量，常见的副作用包括腹泻、呕吐、便秘、腹胀和腹痛。为了提高耐受性，提出了一种改进方案，使用30％MCT和30％长链脂肪酸提供能量，MCT百分比需逐步增加，且功效与经典KD相似，但MCT油价格昂贵，且需要专业营养师培训并通常在医院实施MCT疗法；
3、目前市场中常见的用于干预小鼠模型的不同生酮饲料中的主要蛋白质来源为酪氨酸(casein)，而酪蛋白中的A1酪蛋白在胃肠道消化过程中产生阿片肽，研究发现，BCM-7只来源于A1β-酪蛋白。BCM-7与部分婴儿的Ⅰ型糖尿病风险升高、免疫反应、消化功能紊乱、自闭症和呼吸功能障碍之间存在关联；使用大豆油作为脂肪的主要来源，而大豆油富含ω-6脂肪酸，高ω-6/ω-3比率可能会促进炎症与氧化，加速疾病的进程。
针对这些缺点，本发明旨在提供一种适口性好、容易维持，且能够改善自闭症核心症状的生酮饮食组合物。
发明内容
本发明的目的是克服现有技术中限制性强、适口性差、不耐受、难以维持、疗效参差不齐、副作用多等问题。
为此，本发明提供了一种生酮饮食组合物，以质量百分比计，包括：12±5％乳清蛋白，8-10％纤维素(BW200)，1-2％鱼油；0.5-1％亚麻籽油，1-2％ C8中链脂肪酸油，60-65％可可脂，1-2％矿物质(Mineral Mix S10026)，2％磷酸氢钙，1％碳酸钙，2-3％柠檬酸钾，0.1-0.2％维生素C(V10001C)，0.3-0.5％酒石酸氢胆碱等。
具体的，上述蛋白质为乳清蛋白。
具体的，上述碳水化合物包括甘露糖、核糖、甘露糖、核糖中的至少一种。
具体的，上述脂肪包括鱼油、亚麻籽油、中链甘油三酯中的至少一种。
具体的，上述维生素和矿物质复合物包括1-2％矿物质(Mineral Mix S10026)和0.1-0.2％维生素C(V10001C)。
本发明还提供了上述生酮饮食组合物的制备方法，包括以下步骤：
a)按照权利要求书1中的各组分进行精准称量，添加水量的无菌水按照一定的比例混合后，充分搅拌成团；
b)将混匀的饲料团块置于制粒机中，之称直径为12.5mm，长度为4cm的粒状；
c)将制备好的粒状饲料送入干燥房干燥1-2天；
d)干燥后的饲料进行γ射线辐照1-2天；
e)辐照后进行无菌包装同时进行辐照效果检测(如，物理检测，微生物检测等)。
与现有技术相比，本发明具有以下优点和有益效果：
本发明提供的这种生酮饮食组合物适口性好且容易维持，能够缓解自闭症模型小鼠的社交障碍、重复刻板行为等核心症状。该生酮饮食组合物以乳清作为蛋白质来源可提高抗氧化剂谷胱甘肽的含量，提高饮食的耐受性及优化机体蛋白质的来源；组合鱼油和亚麻籽油是抗炎omega-3脂肪酸的最佳来源；C8 MCT油可改善酮体生成；甘露糖和核糖与低GI淀粉相比，低GI没有果糖的有害影响且可改善适口性；甘露糖具有抗炎作用，核糖可支持线粒体功能，改善体内的能量平衡。
以下将结合附图对本发明做进一步详细说明。
附图说明
图1是小鼠饲喂阶段的体重变化示意图。
图2是自闭症小鼠饲喂不同饲料的血酮与血糖含量变化示意图。
图3是小鼠饲喂不同饲料的社交行为变化示意图。
具体实施方式
下面将结合实施例对本发明中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。尽管已经详细描述了本发明的代表性实施例，但是本发明所属技术领域的普通技术人员将理解，在不脱离本发明范围的情况下可以对本发明进行各种修改和改变。因此，本发明的范围不应局限于实施方案，而应由所附权利要求及其等同物来限定。
下面通过具体实施例对本发明的生酮饮食组合物的效果进行研究。
实施例1：
本实施例提供了一种生酮饮食组合物，包括：12±5％乳清蛋白，8-10％纤维素(BW200)，1-2％鱼油；0.5-1％亚麻籽油，1-2％ C8中链脂肪酸油，60-65％可可脂，1-2％矿物质(Mineral Mix S10026)，2％磷酸氢钙，1％碳酸钙，2-3％柠檬酸钾，0.1-0.2％维生素C(V10001C)，0.3-0.5％酒石酸氢胆碱等。
选取C57 BL/6J小鼠与自闭症模型小鼠作为实验小鼠，采用常规饲喂条件，在6周龄时进行不同饮食的干预，其中：
标准饲料-C57 BL/6J小鼠：饲喂标准小鼠饲料；
生酮组合物-C57 BL/6J小鼠：饲喂本实施例提供的生酮饮食组合物；
标准饲料-自闭症小鼠：饲喂标准小鼠饲料；
生酮组合物-自闭症小鼠：饲喂本实施例提供的生酮饮食组合物。
干预周期为27天，期间对饲喂生酮组合物的小鼠进行体重监测，每隔2天称量一次体重，并进行统计。结果如图1所示，生酮饮食干预对野生鼠和自闭症模型鼠的体重影响不大，没有差异。
干预结束后，对饲喂不同饲料的自闭症小鼠进行12小时禁食，之后进行血糖与血酮的监测，并进行统计。结果如图2所示，生酮饮食干预可明显增加自闭症模型鼠的酮体生成水平，血糖含量不受影响。
对各组小鼠的社交行为采用经典的三箱社交实验进行检测，具体操作步骤：实验开始前，将小鼠放在行为测试室适应30min；用透明的玻璃树脂板将3个箱体隔开，并将测试小鼠放进中间的箱子里适应5min；之后去掉隔开箱子的玻璃树脂板，使测试小鼠可以在三个箱子中自由活动10min，记为自由探索阶段；之后将Stranger 1小鼠(S1)随机放进左侧或右侧箱子里的金属笼子里，另外一侧箱子的金属笼子(E)空着，让小鼠自由探索10min,，记为检测小鼠社交偏好阶段；之后把Stranger2小鼠(S2)空金属笼中，让小鼠自由探索10min,，记为检测小鼠社交新奇性阶段。记录受试小鼠进入每个箱体的持续时间，当小鼠的头和四爪都进入一个箱子就认为它处在那个箱子中。录制小鼠在箱体中的行为表现，并进行视频分析与统计，以野生型小鼠与自闭症小鼠之间的行为差异来展示部分数据分析，结果如图3所示。正常小鼠会表现出社交行为，而自闭症小鼠的社交行为明显表现出异常，但经过生酮饮食的干预后发现，普通野生小鼠表现出更喜欢社交的趋势，且自闭症小鼠的社交障碍现象明显得到好转。通过以上实验结果，可以高效准确地说明喂食本发明提供的生酮饮食组合物后，自闭症小鼠的社交障碍得到改善。
以上例举仅仅是对本发明的举例说明，并不构成对本发明的保护范围的限制，凡是与本发明相同或相似的设计均属于本发明的保护范围之内。
Claims (7)
1.一种生酮饮食组合物，其特征在于，以质量百分比计，包括：12±5％乳清蛋白，8-10％纤维素，1-2％鱼油；0.5-1％亚麻籽油，1-2％C8中链脂肪酸油，60-65％可可脂，1-2％矿物质，2％磷酸氢钙，1％碳酸钙，2-3％柠檬酸钾，0.1-0.2％维生素C，0.3-0.5％酒石酸氢胆碱。
2.如权利要求1所述的生酮饮食组合物，其特征在于：所述蛋白质来源主要为乳清蛋白。
3.如权利要求1所述的生酮饮食组合物，其特征在于：抗炎omega-3脂肪酸的最佳来源是鱼油和亚麻籽油。
4.如权利要求1所述的生酮饮食组合物，其特征在于：所述脂肪包括鱼油、亚麻籽油、中链甘油三酯中的至少一种，其中可改善酮体生成的为C8中链甘油三酯油。
5.如权利要求1所述的生酮饮食组合物，其特征在于：所述维生素和矿物质复合物包括1-2％矿物质和0.1-0.2％维生素C。
6.如权利要求1-5所述的生酮饮食组合物的制备方法，其特征在于，包括以下步骤：
a)按照权利要求书1中的各组分进行精准称量，添加水量的无菌水充分搅拌成团；
b)将混匀的饲料团块制成直径为12.5mm，长度为4cm的粒状；
c)将制备好的粒状饲料送入干燥房干燥1-2天；
d)干燥后的饲料进行γ射线辐照1-2天；
e)辐照后进行无菌包装同时进行辐照效果检测。
7.如权利要求1-5所述的生酮饮食组合物在改善自闭症动物症状中的应用。
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