CN115304664A - 具有改善睡眠功效的酪蛋白肽及其制备方法与应用 - Google Patents
具有改善睡眠功效的酪蛋白肽及其制备方法与应用 Download PDFInfo
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- CN115304664A CN115304664A CN202210744521.2A CN202210744521A CN115304664A CN 115304664 A CN115304664 A CN 115304664A CN 202210744521 A CN202210744521 A CN 202210744521A CN 115304664 A CN115304664 A CN 115304664A
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- Virology (AREA)
Abstract
本发明公开了具有改善睡眠功效的酪蛋白肽及其制备方法与应用,所述酪蛋白肽一级结构氨基酸序列分别为Tyr‑Pro‑Val‑Glu‑Pro(YPVEP),Pro‑Val‑Glu‑Pro‑Phe(PVEPF)及Pro‑Val‑Glu‑Pro(PVEP),分子量分别为603.66Da,587.66Da,440.49Da。本发明的酪蛋白肽既可以通过化学合成法等方式合成,也可以从酪蛋白中定向制备。本发明的酪蛋白肽能与GABAA受体结合,极显著增强戊巴比妥钠诱导小鼠睡眠时间,提高小鼠入睡率,从而表现出改善睡眠活性,可以用于制备具有改善睡眠功效的药物或保健品中。
Description
技术领域
本发明属于氨基酸多肽领域,具体涉及具有改善睡眠功效的酪蛋白肽及其制备方法与应用。
背景技术
随着人们生活节奏的加快,以及近年来新冠肺炎疫情带来的压力和恐慌的积累,失眠和焦虑逐渐成为困扰全球许多人的十大流行精神障碍的前两名。失眠是最常见的精神障碍之一,据统计全世界范围内睡眠障碍的平均患病率已超过35%。目前临床治疗睡眠障碍的方法包括心理疗法和药物疗法(如行为策略、认知疗法、苯二氮卓类药物(BZDs)、抗组胺药、抗抑郁药和褪黑激素)。其中代表性的GABA受体是临床上治疗失眠和焦虑的药物的有效治疗靶点,常用的治疗药物有地西泮、苯二氮平等GABA受体激动剂。它们通常会造成高昂的费用,短期的治疗效果和不必要的副作用。因此,人们越来越关注天然的和食物来源的改善睡眠物质。
现有技术US2011/0312892A1公开含抗焦虑十肽YLGYLEQLLR(α-CZP)的酪蛋白胰蛋白酶酶解物,已证明该酶解物具有显著延长大鼠戊巴比妥钠诱导睡眠时间的效果。同时专利US8685933B2公开几种酪蛋白十肽及其同源系列肽,具有抗焦虑活性,但是酪蛋白中是否含有其他具有改善睡眠活性的肽尚且未知。此外,据报道,大多数睡眠促进物质来自天然补充剂中的草药资源,只有极少数来自生物活性肽。已发表的中国专利一种具有改善睡眠功能的保健食品片剂表明两种纯中药成分缬草和甘草复配具有改善睡眠功效。同时中国专利申请公开了一种改善睡眠质量的口服液的制备方法,主要成分为人参、酸枣仁、大枣、益智仁、陈皮等中草药成分。然而这两篇专利主要侧重在于有效成分的简单复配,并没有发现原创性成分,而且活性成分均来自中草药成分。因此,目前关于食源性的改善睡眠活性多肽开发研究,还十分不足。
发明内容
本发明的首要目的在于提供具有改善睡眠功效的酪蛋白肽,包括YPVEP,PVEPF和PVEP。
本发明的另一目的在于提供上述具有改善睡眠功效的酪蛋白肽的定向制备方法及其应用。
本发明的目的通过下述技术方案之一实现。
本发明提供具有改善睡眠功效的酪蛋白肽,所述酪蛋白肽包括的氨基酸序列分别为Tyr-Pro-Val-Glu-Pro(YPVEP,f129-134)(SEQ.ID.NO.1),Pro-Val-Glu-Pro-Phe(PVEPF,f130-134)(SEQ.ID.NO.2)及Pro-Val-Glu-Pro(PVEP,f130-133)(SEQ.ID.NO.3),分子量分别为603.66Da,587.66Da,440.49Da。
进一步地,所述具有改善睡眠功效的酪蛋白肽SEQ.ID.NO.1~3可通过化学合成法等方式合成。
本发明提供具有改善睡眠功效的酪蛋白肽SEQ.ID.NO.1~3通过定向酶解制备方法获得,所述具有改善睡眠功效的酪蛋白肽的制备方法,包括如下步骤:
(1)酪蛋白酶解:将酪蛋白与水按质量比1:6~1:12加水搅拌,升温至37~50℃,分步加入酪蛋白质量0.05%~3.0%的蛋白酶和酪蛋白质量0.5%~4.0%的消化酶,进行两步酶解,共3~8h,升温灭酶,酶解结束,酶解液经过滤浓缩和喷雾干燥获得酪蛋白酶解物;
(2)将步骤(1)得到的酪蛋白酶解物通过高效液相色谱联用质谱法鉴定,得到YPVEP、PVEPF和PVEP,分别为SEQ.ID.NO.1、SEQ.ID.NO.2和SEQ.ID.NO.3(SEQ.ID.NO.1~3)。
进一步地,步骤(1)所述酪蛋白的来源包括牛乳、羊乳、骆驼乳、马乳中的一种以上。
进一步地,步骤(1)所述蛋白酶包括木瓜蛋白酶、碱性蛋白酶或胰凝乳蛋白酶中的一种以上。
进一步地,步骤(1)所述消化酶包括胃蛋白酶和胰酶中的一种以上。
优选地,步骤(1)所述蛋白酶包括木瓜蛋白酶或胰凝乳蛋白酶,消化酶为胃蛋白酶复配胰酶。
进一步地,步骤(1)中加入蛋白酶的质量为加入酪蛋白质量0.1%~2.0%。
进一步地,步骤(1)中加入消化酶的质量为加入酪蛋白质量0.5%~3.0%。
进一步地,步骤(1)所述两步酶解具体指:第一步蛋白酶酶解1~4h,第二步消化酶酶解2~4h。
进一步地,步骤(1)所述升温灭酶的条件为:升温至100℃,煮沸15min。
进一步地,步骤(1)所述酪蛋白酶解物,还可以进一步通过分离纯化具体包括高效液相色谱法、醇沉法、凝胶色谱法中的一种分离获得本发明的三种具有改善睡眠功效的酪蛋白肽。
进一步地,步骤(1)中由酶解制备得到得酪蛋白酶解物应用于药物或保健品中。
进一步地,步骤(2)通过高效液相色谱联用质谱法鉴定,得到5.3min(YPVEP),6.8min(PVEPF),3.8min(PVEP)时出峰。
本发明还提供所述具有改善睡眠功效的酪蛋白肽在制备具有改善睡眠功效的药物或保健品物中的应用。
进一步地,所述药物或保健品还含有其他具有改善睡眠功效的活性成分和/或可接受的辅料。
进一步地,所述具有改善睡眠功效的活性成分为脱脂奶粉、γ-氨基丁酸、茶氨酸、胶原蛋白肽、酸枣仁中的一种以上;所述可接受的辅料包括麦芽糊精、山梨糖醇、微晶纤维素中的一种以上。
进一步地,所述药物或保健品是粉末冲剂、功能饮料、压片糖果、凝胶软糖、口服液中的一种以上。
进一步地,具有改善睡眠功效的酪蛋白肽在药物或保健品中应用,所述应用具体包括以下几种形式:
(1)直接用于冲剂、片剂、压片或凝胶糖果等形式,所述酪蛋白肽的纯化组分浓缩液的喷雾干燥粉末、麦芽糊精和山梨糖醇混合后进行过筛、造粒、喷雾干燥后制得组合物;
(2)与其他具有改善睡眠或抗焦虑功效的活性成分和/或可接受的辅料,所述具有改善睡眠功效的活性成分为脱脂奶粉、γ-氨基丁酸、茶氨酸、酸枣仁、胶原蛋白肽等中的一种以上;所述可接受的辅料包括麦芽糊精、山梨糖醇、微晶纤维素等中的一种以上。
本发明相对于现有技术具有如下优点和有益效果:
本发明的具有改善睡眠功效的酪蛋白肽能提高戊巴比妥钠诱导小鼠的入睡率,极显著延长戊巴比妥钠诱导小鼠睡眠时间,从而表现出改善睡眠的活性,可以用于制备具有改善睡眠功效的药物或保健品。
本发明的定向酶解制备法可以快速定位到具有改善睡眠功效的目标酪蛋白肽段,并定向酶解,达到高效释放,所制的酪蛋白肽能显著延长戊巴比妥钠诱导小鼠睡眠时间,具有较强的改善睡眠活性。
附图说明
图1为酪蛋白肽YPVEP,PVEPF和PVEP对戊巴比妥钠诱导小鼠睡眠行为学实验中睡眠时间的影响柱状图。
图2为酪蛋白肽YPVEP,PVEPF和PVEP对戊巴比妥钠诱导小鼠睡眠行为学实验中入睡率的影响柱状图。
图3为实施例3-5中酪蛋白酶解物对戊巴比妥钠诱导小鼠睡眠行为学实验中睡眠时间的影响柱状图。
图4为实施例3-5中酪蛋白酶解物对戊巴比妥钠诱导小鼠睡眠行为学实验中入睡率的影响柱状图。
图5为具有改善睡眠功效的酪蛋白肽YPVEP,PVEPF和PVEP的二级谱图。
具体实施方式
以下结合附图和实例对本发明的具体实施作进一步说明,但本发明的实施和保护不限于此。需指出的是,以下若有未特别详细说明之过程,均是本领域技术人员可参照现有技术实现或理解的。所用试剂或仪器未注明生产厂商者,视为可以通过市售购买得到的常规产品。
下列实施例中涉及的实验方法:
(1)延长戊巴比妥钠睡眠时间实验
参考《保健食品检验与评价技术规范》中第十章、改善睡眠功能检验方法进行测定。(其中空白对照组为口服灌胃相同剂量的超纯水,阳性对照组为腹腔注射1mg/kg的安定类药物地西泮,而其他样品多肽组别均设置口服灌胃1.8mg/kg,0.1mL/10g)
(2)质谱鉴定方法
使用超高效液相色谱联用质谱(UPLC-MS/MS)鉴定生物活性肽,采用梯度洗脱色谱分离,联用二级质谱鉴定并定量,洗脱速度为0.2mL/min,进样量为2μL。流动相A为体积百分比浓度0.1%甲酸水,B为乙腈(色谱纯),洗脱程序为:0~10min,5%~40%B;10~12min,40%~90%B;12~14min,90%B;14~15min,90%~5%B;15~18min,5%B平衡至初始状态。质谱参数:电子轰击离子源能量7eV,毛细管电压4500V,离子源温度200℃,干燥气体流量8.0L/min,雾化器压力1.5bar,质量扫描范围m/z 50~1500。
实施例1
酪蛋白肽YPVEP,PVEPF和PVEP(SEQ.ID.NO.1~3),口服灌胃剂量均为1.8mg/kg时,其戊巴比妥钠诱导小鼠睡眠时间分别为1861.71±159.21s,612±212.99s,222.17±44.98s。
对比例1
已报道改善睡眠活性十肽α-CZP(YLGYLEQLLR),口服灌胃剂量为1.8mg/kg时,其戊巴比妥钠诱导小鼠睡眠时间为338.72±104.38s。
可见,本发明酪蛋白肽YPVEP及PVEPF的延长戊巴比妥钠诱导小鼠睡眠时间活性较强。
实施例2
酪蛋白肽YPVEP,PVEPF和PVEP(SEQ.ID.NO.1~3),口服灌胃剂量均为1.8mg/kg时,其戊巴比妥钠诱导小鼠入睡率分别为58.33%,58.33%,50%。
对比例2
已报道改善睡眠活性十肽α-CZP(YLGYLEQLLR),口服灌胃剂量为1.8mg/kg时,其戊巴比妥钠诱导小鼠入睡率为50%。
可见,本发明酪蛋白肽YPVEP及PVEPF的提高戊巴比妥钠诱导小鼠入睡率活性较强。
实施例3
(1)酪蛋白酶解:将100g酪蛋白与600g水按质量比1:6加水搅拌,升温至50℃,分步加入酪蛋白质量3.0%的碱性蛋白酶(pH 8.0,50℃,酶解1h)和酪蛋白质量0.5%的胰酶(pH7.0,37℃,酶解2h),进行两步酶解,共3h后升温至100℃,煮沸15min,酶解液经过滤浓缩和喷雾干燥获得酪蛋白酶解物;
(2)得到的酪蛋白酶解物通过高效液相色谱联用质谱法鉴定,得到5.3min(YPVEP),6.8min(PVEPF),3.8min(PVEP)时出峰,分别为SEQ.ID.NO.1~3。
实施例4
(1)酪蛋白酶解:将100g酪蛋白与1000g水按质量比1:10加水搅拌,升温至50℃,分步加入酪蛋白质量1.0%的木瓜蛋白酶(pH 8.0,50℃,酶解4h)和酪蛋白质量2.0%的胃蛋白酶复配酪蛋白质量1.0%的胰酶(pH 7.0,37℃,酶解4h),进行两步酶解,共8h后升温至100℃,煮沸15min,酶解液经过滤浓缩和喷雾干燥获得酪蛋白酶解物;
(2)得到的酪蛋白酶解物通过高效液相色谱联用质谱法鉴定,得到5.3min(YPVEP),6.8min(PVEPF),3.8min(PVEP)时出峰,分别为SEQ.ID.NO.1~3。
实施例5
(1)酪蛋白酶解:将100g酪蛋白与1200g水按质量比1:12加水搅拌,升温至50℃,分步加入酪蛋白质量0.05%的胰凝乳蛋白酶(pH 8.0,50℃,酶解2h)和酪蛋白质量4.0%的胃蛋白酶(pH 7.0,37℃,酶解4h),进行两步酶解,共6h后升温至100℃,煮沸15min,酶解液经过滤浓缩和喷雾干燥获得酪蛋白酶解物;
(2)得到的酪蛋白酶解物通过高效液相色谱联用质谱法鉴定,得到5.3min(YPVEP),6.8min(PVEPF),3.8min(PVEP)时出峰,分别为SEQ.ID.NO.1~3。
对比例3
(1)酪蛋白酶解:将100g酪蛋白与1000g水按质量比1:10加水搅拌,升温至50℃,分步加入酪蛋白质量4.0%的中性蛋白酶(pH 8.0,50℃),酶解6h后升温至100℃,煮沸15min,酶解液经过滤浓缩和喷雾干燥获得酪蛋白酶解物;
(2)得到的酪蛋白酶解物通过高效液相色谱联用质谱法鉴定,无法得到肽序列SEQ.ID.NO.1~3。
图1为酪蛋白肽YPVEP,PVEPF和PVEP对戊巴比妥钠诱导小鼠睡眠行为学实验中睡眠时间的影响柱状图。由图1可知,戊巴比妥钠诱导小鼠睡眠实验中,空白对照组睡眠时间为138.60±70.30s,与空白对照组相比,阳性对照地西泮组(2506.18±334.76s)、实施例1中各酪蛋白肽口服灌胃组极显著延长戊巴比妥钠诱导小鼠睡眠时间(p<0.01)。本发明酪蛋白肽YPVEP及PVEPF与已报道改善睡眠十肽α-CZP相比,改善睡眠活性显著较强,同时与空白对照组相比,本发明三条改善睡眠酪蛋白肽均能够有效延长小鼠睡眠时间。
图2为酪蛋白肽YPVEP,PVEPF和PVEP对戊巴比妥钠诱导小鼠睡眠行为学实验中入睡率的影响柱状图。由图2所示,戊巴比妥钠诱导小鼠睡眠实验中,空白对照组入睡率为41.67%,与空白对照组相比,阳性对照地西泮组(91.67%)、实施例1中各酪蛋白肽口服灌胃组均能提高戊巴比妥钠诱导小鼠入睡率。本发明酪蛋白肽YPVEP及PVEPF与已报道改善睡眠十肽α-CZP相比,改善睡眠活性显著较强,同时与空白对照组相比,本发明三条改善睡眠酪蛋白肽均能够有效提高小鼠入睡率。
图3为实施例3-5酪蛋白酶解物对戊巴比妥钠诱导小鼠睡眠行为学实验中睡眠时间的影响柱状图。由图3所示,戊巴比妥钠诱导小鼠睡眠实验中,空白对照组睡眠时间为177.00±84.24s,与空白对照组相比,阳性对照地西泮组(2206.88±946.84s)、实施例3-5中酪蛋白酶解物均可不同程度的显著延长戊巴比妥钠诱导小鼠睡眠时间(p<0.01),这表明本发明定向制备的含SEQ.ID.NO.1~3肽的酪蛋白酶解物也能够有效延长小鼠睡眠时间。而对比例3中的酪蛋白酶解物与空白对照组相比,不能显著延长小鼠睡眠时间。
图4为实施例3-5中酪蛋白酶解物对戊巴比妥钠诱导小鼠睡眠行为学实验中入睡率的影响柱状图。由图4所示,戊巴比妥钠诱导小鼠睡眠实验中,空白对照组入睡率为41.67%,与空白对照组相比,阳性对照地西泮组(91.67%)、实施例3-5中各组分均可不同程度的提高戊巴比妥钠诱导小鼠入睡率,这表明本发明定向制备的含SEQ.ID.NO.1~3肽的酪蛋白酶解物也均能够有效提高小鼠入睡率。而对比例3中的酪蛋白酶解物与空白对照组相比,不能提高小鼠入睡率。
图5为具有改善睡眠功效的酪蛋白肽YPVEP,PVEPF和PVEP的二级谱图。由图5可知本发明的制备方法分离得到的酪蛋白肽序列经鉴定为SEQ.ID.NO.1~3。
以上实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
序列表
<110> 华南理工大学
广东华肽生物科技有限公司
<120> 具有改善睡眠功效的酪蛋白肽及其制备方法与应用
<160> 3
<170> SIPOSequenceListing 1.0
<210> 11
<211> 5
<212> PRT
<213> 酪蛋白(Casein)
<400> 11
Tyr Pro Val Glu Pro
1 5
<210> 2
<211> 5
<212> PRT
<213> 酪蛋白(Casein)
<400> 2
Pro Val Glu Pro Phe
1 5
<210> 3
<211> 4
<212> PRT
<213> 酪蛋白(Casein)
<400> 3
Pro Val Glu Pro
1
Claims (10)
1.具有改善睡眠功效的酪蛋白肽,其特征在于,所述酪蛋白肽包括的氨基酸序列为Tyr-Pro-Val-Glu-Pro,记为SEQ.ID.NO.1;Pro-Val-Glu-Pro-Phe,记为SEQ.ID.NO.2;Pro-Val-Glu-Pro,记为SEQ.ID.NO.3。
2.权利要求1所述具有改善睡眠功效的酪蛋白肽的制备方法,其特征在于,通过以下酶解工艺步骤获得:
(1)酪蛋白酶解:将酪蛋白与水按质量比1:6~1:12加水搅拌,升温至37~50℃,分步加入酪蛋白质量0.05%~3.0%的蛋白酶和酪蛋白质量0.5%~4.0%的消化酶,进行两步酶解,共3~8h,升温灭酶,酶解结束,酶解液经过滤浓缩和喷雾干燥获得酪蛋白酶解物;
(2)将步骤(1)得到的酪蛋白酶解物通过高效液相色谱联用质谱法鉴定,得到YPVEP、PVEPF和PVEP,分别记为SEQ.ID.NO.1、SEQ.ID.NO.2和SEQ.ID.NO.3。
3.根据权利要求2所述具有改善睡眠功效的酪蛋白肽的制备方法,其特征在于,步骤(1)所述酪蛋白的来源包括牛乳、羊乳、骆驼乳、马乳中的一种以上。
4.根据权利要求2所述具有改善睡眠功效的酪蛋白肽的制备方法,其特征在于,步骤(1)所述蛋白酶包括木瓜蛋白酶、碱性蛋白酶或胰凝乳蛋白酶中的一种以上。
5.根据权利要求2所述具有改善睡眠功效的酪蛋白肽的制备方法,其特征在于,步骤(1)所述消化酶包括胃蛋白酶和胰酶中的一种以上。
6.根据权利要求2所述具有改善睡眠功效的酪蛋白肽的制备方法,其特征在于,步骤(1)所述两步酶解具体指:第一步蛋白酶酶解1~4h,第二步消化酶酶解2~4h。
7.权利要求1所述具有改善睡眠功效的酪蛋白肽在制备具有改善睡眠功效的药物或保健品中的应用。
8.根据权利要求7所述的应用,其特征在于,所述药物或保健品含有其他具有改善睡眠功效的活性成分和/或可接受的辅料。
9.根据权利要求8所述的应用,其特征在于,所述具有改善睡眠功效的活性成分为脱脂奶粉、γ-氨基丁酸、茶氨酸、胶原蛋白肽、酸枣仁中的一种以上;所述可接受的辅料包括麦芽糊精、山梨糖醇、微晶纤维素中的一种以上。
10.根据权利要求7所述的应用,其特征在于,所述药物或保健品是粉末冲剂、功能饮料、压片糖果、凝胶软糖、口服液中的一种以上。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117482214A (zh) * | 2023-10-23 | 2024-02-02 | 广州绿萃生物科技有限公司 | 一种改善中老年失眠的水解酪蛋白肽及其制备方法和应用 |
CN117964692A (zh) * | 2024-02-04 | 2024-05-03 | 杭州康源食品科技有限公司 | 一种具有助睡眠活性的五肽及其应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101525376A (zh) * | 2009-04-17 | 2009-09-09 | 天津商业大学 | αs1-酪蛋白来源的阿片肽(AOPP)及其制备方法 |
JP2015084694A (ja) * | 2013-10-29 | 2015-05-07 | 森永乳業株式会社 | ジペプチジルペプチダーゼ−iv阻害剤 |
CN107987149A (zh) * | 2017-12-29 | 2018-05-04 | 澳优乳业(中国)有限公司 | 一种生物活性肽、寡聚核苷酸及其制备方法和应用 |
CN112056453A (zh) * | 2020-08-31 | 2020-12-11 | 华南理工大学 | 一种富含芳香族氨基酸的改善睡眠酶解物及其制备方法 |
CN114106096A (zh) * | 2021-11-16 | 2022-03-01 | 华南理工大学 | 一种具有改善睡眠活性的六肽及其应用 |
CN114181292A (zh) * | 2021-11-01 | 2022-03-15 | 华南理工大学 | 一种高溶解性酪蛋白改善睡眠肽及其制备工艺与应用 |
-
2022
- 2022-06-28 CN CN202210744521.2A patent/CN115304664A/zh active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101525376A (zh) * | 2009-04-17 | 2009-09-09 | 天津商业大学 | αs1-酪蛋白来源的阿片肽(AOPP)及其制备方法 |
JP2015084694A (ja) * | 2013-10-29 | 2015-05-07 | 森永乳業株式会社 | ジペプチジルペプチダーゼ−iv阻害剤 |
CN107987149A (zh) * | 2017-12-29 | 2018-05-04 | 澳优乳业(中国)有限公司 | 一种生物活性肽、寡聚核苷酸及其制备方法和应用 |
CN112056453A (zh) * | 2020-08-31 | 2020-12-11 | 华南理工大学 | 一种富含芳香族氨基酸的改善睡眠酶解物及其制备方法 |
CN114181292A (zh) * | 2021-11-01 | 2022-03-15 | 华南理工大学 | 一种高溶解性酪蛋白改善睡眠肽及其制备工艺与应用 |
CN114106096A (zh) * | 2021-11-16 | 2022-03-01 | 华南理工大学 | 一种具有改善睡眠活性的六肽及其应用 |
Non-Patent Citations (3)
Title |
---|
BLANCA HERNA Ä NDEZ-LEDESMA: "Angiotensin Converting Enzyme Inhibitory Activity in Commercial Fermented Products. Formation of Peptides under Simulated Gastrointestinal Digestion", J. AGRIC. FOOD CHEM., vol. 52, 17 February 2004 (2004-02-17), pages 1504 - 1510 * |
JINGJING QIAN ET AL.: "Identification and Screening of Potential Bioactive Peptides with Sleep-Enhancing Effects in Bovine Milk Casein Hydrolysate", J AGRIC FOOD CHEM ., vol. 69, 20 September 2021 (2021-09-20), pages 11246 * |
YASUHISA ANO ET AL.: "Identi fi cation of a Novel Peptide from β‑Casein That Enhances Spatial and Object Recognition Memory in Mice", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 67, 26 June 2019 (2019-06-26), pages 8160 - 8167 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117482214A (zh) * | 2023-10-23 | 2024-02-02 | 广州绿萃生物科技有限公司 | 一种改善中老年失眠的水解酪蛋白肽及其制备方法和应用 |
CN117964692A (zh) * | 2024-02-04 | 2024-05-03 | 杭州康源食品科技有限公司 | 一种具有助睡眠活性的五肽及其应用 |
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