CN111568881A - 一种核壳体缓释氨基酸补剂及其制备方法 - Google Patents
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Abstract
本发明公开了一种核壳体缓释氨基酸补剂及其制备方法,核壳体缓释氨基酸包括氨基酸内核和包裹在氨基酸内核外侧的一层或多层外壳,其中一层或多层外壳材料为昆布多糖,制备方法包括:低温条件下,将氨基酸进行超微粉碎,一次包裹,干燥后二次包裹,干燥后三次包裹,最后得到三层外壳的核壳结构体缓释氨基酸补剂。本发明利用昆布多糖包裹氨基酸微粒,使其形成核壳结构,通过调节包裹物的浓度和包裹层的厚度来调节氨基酸在人体内的半衰期,提高氨基酸的利用率;昆布多糖具有多种药理作用,其包裹氨基酸,既能解决氨基酸服用后半衰期短的问题,又符合中医药食同源的养生理念。
Description
技术领域
本发明涉及氨基酸制剂技术领域,具体为一种核壳体缓释氨基酸补剂及其制备方法。
背景技术
氨基酸是构成蛋白质的基本单位,是分子中具有氨基和羧基的一类含有复合基团的化合物,参与机体的生化反应和生理机能过程,是人体最重要的营养物质之一,组成人体蛋白质的氨基酸有20多种,但人体本身不能全部自己合成,需要通过饮食进行补充,如果人体不能补充足够的必需氨基酸,将会严重影响身体的正常发育、生长性能、抗应激能力、抗病力和免疫水平。
必需氨基酸一般可以通过合理的饮食搭配补充,但很多人由于不合理的饮食导致氨基酸补充不足,需要服用氨基酸营养剂进行补充。现有技术中,氨基酸营养剂服用后,在人体内半衰期较短,导致氨基酸利用率不足,因此,需要研究一种缓释氨基酸补剂来解决这种问题。
发明内容
针对上述问题,本发明提供一种核壳体缓释氨基酸补剂及其制备方法,利用昆布多糖包裹氨基酸微粒,使其形成核壳结构,通过调节包裹物的浓度和包裹层的厚度来调节氨基酸在人体内的半衰期,提高氨基酸的利用率。
为了实现上述目的,本发明采用以下技术方案
一种核壳体缓释氨基酸补剂,其包括氨基酸内核和包裹在氨基酸内核外侧的一层或多层外壳,其中一层或多层外壳材料为昆布多糖。
优选地,所述核壳体缓释氨基酸补剂为一层核壳结构,包括氨基酸内核和包裹氨基酸内核的昆布多糖外壳。
优选地,所述核壳体缓释氨基酸补剂为三层核壳结构,包括氨基酸内核、包裹物为昆布多糖的第一层外壳、包裹物为淀粉的第二层外壳和包裹物为昆布多糖的第三层外壳。
优选地,所述第一层外壳的厚度小于第二层外壳,且第二层外壳的厚度小于第三层外壳。
优选地,所述氨基酸内核为氨基酸的环糊精包合物。
一种核壳体缓释氨基酸补剂的制备方法,包括以下步骤:
S1、低温条件下,将氨基酸进行超微粉碎,粉碎后过600-1000目筛,得到氨基酸微粒;
S2、将昆布多糖投入去离子水中,均质后,对氨基酸微粒进行包裹,得到一层结构包裹物;
S3、将S2产生的一层结构包裹物进行干燥处理,之后将水溶淀粉投入去离子水中,均质后,对一层结构包裹物进行二次包裹,得到二层结构包裹物;
S4、将S3产生的二层结构包裹物进行干燥处理,之后将昆布多糖投入去离子水中,均质后,对二层结构包裹物进行包裹,得到三层结构包裹物;
S5、将S4产生的三层包裹物进行干燥处理,得到三层外壳的核壳结构体缓释氨基酸补剂。
优选地,S2、S3和S4中,采用雾化喷涂技术进行包裹,喷涂工艺为:进风温度60-75℃,风量40-60m3/h,雾化压力0.3-0.5MPa,流速10-20ml/min。
优选地,S2、S3和S4中,包裹时采用超声波辅助,超声波频率50k-100kHz。
优选地,S3、S4和S5中,烘干温度为75-90℃,时间为20-40min。
优选地,S2中,昆布多糖与去离子水的重量比为(2-5):8;S4中,昆布多糖与去离子水的重量比为(4-6):8。
优选地,S2、S4中,昆布多糖与去离子水均质时,温度为40-60℃。
昆布多糖(Laminarin)又称海带多糖、褐藻淀粉,主要有褐藻(如褐藻酸钠,又称褐藻胶,在海带中含量约为19.7%)、褐藻淀粉(又称昆布多糖、海藻硫酸多糖、褐藻多糖,在海带中含量约为1%)、褐藻糖胶(又称岩藻糖胶,主要成分为岩藻多糖,又称岩藻聚糖)等3种类型,由β(1-3)-葡聚糖和一些β(1-6)-糖苷键连接组成,是Chemicalbook一种中性葡聚糖,广泛存在于褐藻中,也是翅藻科植物昆布或海带科植物海带中的主要化学成分,具有调节免疫、抗肿瘤、抗凝血、调血脂、降血糖、抗辐射、抗氧化、抑菌、抗病毒等药理作用,同时还具有降低血压、耐疲劳、抗肺间质纤维化、调节酪氨酸激酶活性、抗突变等多种功效。昆布多糖,可以修复肾小球使肾小球保持活力从而减少了其硬化的速度、缓慢的但实实在在的在修复肾小球,可以阻止毛细血管的纤维化趋势,同时可以在小肠将人体吃入的盐分,糖分直接代谢出人体,减少了肾脏的负担,从而起到保护肾脏的作用。
本发明的有益效果:
1、本发明利用昆布多糖包裹氨基酸微粒,使其形成核壳结构,通过调节包裹物的浓度和包裹层的厚度来调节氨基酸在人体内的半衰期,提高氨基酸的利用率。
2、采用喷涂技术进行包裹,通过控制喷涂时间控制涂层的厚度,通过调节超声波的频率,调节涂层的密实度。
3、调节氨基酸微粒、一层核壳结构的氨基酸和三层核壳结构的氨基酸的比例,可以兼顾到氨基酸的及时补充和较长的缓释期,适用于所有需要补充氨基酸的人群。
4、昆布多糖具有多种药理作用,其包裹氨基酸,既能解决氨基酸服用后半衰期短的问题,又符合中医药食同源的养生理念。
附图说明
图1是本发明中一层核壳结构的氨基酸的结构示意图;
图2是本发明中三层核壳结构的氨基酸的结构示意图;
图3是本发明中核壳体缓释氨基酸补剂不同实施例的释放率曲线图。
具体实施方式
下面对本发明实施例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。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其它实施例,都属于本发明保护的范围。
实施例一
一种核壳体缓释氨基酸补剂,核壳体缓释氨基酸为一层核壳结构,包括氨基酸内核和包裹氨基酸内核的昆布多糖外壳。
其制备方法,包括以下步骤:
S1、低温条件下,将氨基酸进行超微粉碎,粉碎后过600-1000目筛,得到氨基酸微粒;
S2、将昆布多糖投入去离子水中,昆布多糖与去离子水的重量比为3:8,进行均质,温度为45℃,均质后,采用雾化喷涂方式对氨基酸微粒进行包裹,得到一层结构包裹物;
S3、将S2产生的一层结构包裹物进行干燥处理,烘干温度为80℃,时间为30min,得到一层外壳的核壳结构体缓释氨基酸补剂。
如图1所示,采用一层昆布多糖对氨基酸微粒进行包裹,减缓氨基酸释放速度,延长其半衰期;同时充分利用了昆布多糖的药理作用。
实施例二
一种核壳体缓释氨基酸补剂,核壳体缓释氨基酸补剂为三层核壳结构,包括氨基酸内核、包裹物为昆布多糖的第一层外壳、包裹物为淀粉的第二层外壳和包裹物为昆布多糖的第三层外壳。
其中,第一层外壳的厚度小于第二层外壳,且第二层外壳的厚度小于第三层外壳。
其制备方法,包括以下步骤:
S1、低温条件下,将氨基酸进行超微粉碎,粉碎后过1000目筛,得到氨基酸微粒;
S2、将昆布多糖投入去离子水中,昆布多糖与去离子水的重量比为3:8,进行均质,温度为45℃,均质后,采用雾化喷涂方式对氨基酸微粒进行包裹,包裹时采用超声波辅助,超声波频率60kHz,得到一层结构包裹物;
S3、将S2产生的一层结构包裹物进行干燥处理,烘干温度为75℃,时间为20min,之后将水溶淀粉投入去离子水中,均质后,采用雾化喷涂方式对一层结构包裹物进行二次包裹,包裹时采用超声波辅助,超声波频率80kHz,得到二层结构包裹物;
S4、将S3产生的二层结构包裹物进行干燥处理,烘干温度为80℃,时间为30min,之后将昆布多糖投入去离子水中,昆布多糖与去离子水的重量比为5:8,进行均质,温度为45℃,均质后,采用雾化喷涂方式对二层结构包裹物进行包裹,包裹时采用超声波辅助,超声波频率100kHz,得到三层结构包裹物;
S5、将S4产生的三层包裹物进行干燥处理,烘干温度为85℃,时间为40min,得到三层外壳的核壳结构体缓释氨基酸补剂。
如图2所示,采用三层外壳对氨基酸微粒进行包裹,其中两层为昆布多糖,其较实施例一进一步减缓氨基酸释放速度,延长其半衰期;同时充分利用了昆布多糖的药理作用。
实施例三
一种核壳体缓释氨基酸补剂,核壳体缓释氨基酸补剂为三层核壳结构,包括氨基酸内核、包裹物为昆布多糖的第一层外壳、包裹物为淀粉的第二层外壳和包裹物为昆布多糖的第三层外壳。
其中,氨基酸内核为氨基酸的环糊精包合物。
其制备方法,包括以下步骤:
S1、低温条件下,将氨基酸进行超微粉碎,粉碎后过800目筛,得到氨基酸微粒,氨基酸微粒进行环糊精包合处理,得到氨基酸的环糊精包合物;
S2、将昆布多糖投入去离子水中,昆布多糖与去离子水的重量比为1:2,进行均质,温度为50℃,均质后,采用雾化喷涂方式对氨基酸的环糊精包合物进行包裹,包裹时采用超声波辅助,超声波频率80kHz,得到一层结构包裹物;
S3、将S2产生的一层结构包裹物进行干燥处理,烘干温度为80℃,时间为20min,之后将水溶淀粉投入去离子水中,均质后,采用雾化喷涂方式对一层结构包裹物进行二次包裹,包裹时采用超声波辅助,超声波频率60kHz,得到二层结构包裹物;
S4、将S3产生的二层结构包裹物进行干燥处理,烘干温度为85℃,时间为30min,之后将昆布多糖投入去离子水中,昆布多糖与去离子水的重量比为3:4,进行均质,温度为50℃,均质后,采用雾化喷涂方式对二层结构包裹物进行包裹,包裹时采用超声波辅助,超声波频率100kHz,得到三层结构包裹物;
S5、将S4产生的三层包裹物进行干燥处理,烘干温度为90℃,时间为40min,得到三层外壳的核壳结构体缓释氨基酸补剂。
先对氨基酸微粒进行环糊精包合处理,再采用三层外壳对氨基酸微粒进行包裹,其中两层为昆布多糖,其较实施例二进一步减缓氨基酸释放速度,延长其半衰期;同时充分利用了昆布多糖的药理作用。
实验例一
核壳体缓释氨基酸缓释性能和半衰期检测:
以必需氨基酸中的赖氨酸为例,分别通过实施例一、实施例二和实施例三制备的缓释氨基酸,记作样品A、样品B和样品C,分别称取0.400g的样品A、样品B和样品C,称取0.400g的赖氨酸微粒,记作对比样品D,分别投入磷酸盐缓冲溶液模拟肠液(pH=7.45)中,于(36.8±0.8)℃以120r/min的速度搅拌,释放360min;每隔一段时间从中吸取1mL溶液,测定赖氨酸的含量,同时补充相同体积的模拟溶液。赖氨酸的含量使用茚三酮显色法,使用紫外-可见分光光度计在570nm处测定,根据测定的溶液赖氨酸含量计算出不同时间的释放百分比。
实验结果,如图3所示,四条曲线分别表示了样品A、样品B、样品C和对比样品D在六个小时内的释放率,从中可得出,样品A、样品B和样品C的释放率明显低于对比样品D,而在样品A、样品B和样品C中,样品C的释放率最低。
实验例二
核壳体缓释氨基酸半衰期检测:
检测方法:
以必需氨基酸中的赖氨酸为例,分别通过实施例一、实施例二和实施例三制备的缓释氨基酸,记作样品A、样品B和样品C,取不做任何处理的赖氨酸微粒,记作对比样品D。
1、取同等重量的家兔四只,样品A、样品B、样品C和对比样品D分别制成饮水后对应喂饮,记录喂食时间。
2、在喂食2小时后抽取家兔耳缘静脉血5ml置于烧杯中,之间每隔2小时抽血一次,共抽取12次,每次抽血前用肝素湿润针管抗凝。
3、用注射器抽取血液,滴入盛有5ml 5%三氯醋酸的试管中,充分摇匀,之后使用离心机离心5min,离心速度为1500rpm/min,之后取上清液标记待用。
4、配制标准液,配制0.03%的样品A、样品B、样品C和对比样品D的溶液各0.5ml,加入盛有5ml 5%三氯醋酸的试管中摇匀待用。
5、配制样品A、样品B、样品C和对比样品D各自对应的比色管。
6、使用使用紫外-可见分光光度计在570nm处测定,根据测定的血液赖氨酸含量计算出样品A、样品B、样品C和对比样品D各自的半衰期。
实验结果:
计算得到,对比样品D的半衰期为21.3小时,样品A的半衰期为27.6小时,样品B的半衰期为34.5小时,样品C的半衰期为39.1小时,由此可得,进行包裹的缓释氨基酸在动物体内的半衰期明显增长。
昆布多糖的药理作用
1.调节免疫功能昆布多糖具有明显的调节机体免疫功能作用。从褐藻中分离的岩藻聚糖能通过两种途径调节补体***:一是通过干扰C1活化或抑制C4裂解为C4b和C4a两个片断以及抑制C4b和C2的相互作用来阻碍经典途径中C3转移酶的形成;二是通过影响裂解素(properdin)的稳定性,抑制B因子与C3b的结合,从而阻止旁路途径中C3转移酶的形成。除了影响补体活性外,褐藻多糖对机体特异性免疫功能也具有明显的增强作用。作为一类重要的免疫功能调节剂,昆布多糖也能明显影响机体的非特异性免疫功能。昆布中的糖脂类物质能够与免疫刺激剂复合物结合,作为脂质体用于微生物及肿瘤抗原的递呈。
2.抗肿瘤作用昆布多糖硫酸酯的抗肿瘤作用机制,除了本身具有直接抑制肿瘤细胞生长外,还可能通过增强机体免疫功能,抑制肿瘤细胞生长扩散。昆布多糖可下调乳腺癌细胞、肝癌细胞Bcl-2蛋白的表达,并可降低5-Fu,MTX,MMC,ADM,CTX的有效治疗剂量;诱导体外HL-60细胞凋亡,其中对凋亡的调控作用可能为负调控;调控NF-κB的表达,其表达有时间差异性。此外,昆布多糖硫酸酯能够干扰肿瘤组织中的Bgfgr血管生成信号刺激作用,使肿瘤组织的血管生成受阻,肿瘤生长受到抑制;能够对抗化疗药物环磷酰胺引起的白细胞减少,具有升高白细胞作用。昆布多糖的抗肿瘤作用机制与直接杀伤肿瘤细胞、诱导细胞凋亡、抑制血管生成及调节机体免疫功能有关。
3.调血脂作用血浆中甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDL)均是动脉粥样硬化形成的促进因子,LDL升高是心肌梗死的危险因子,而高密度脂蛋白(HDL)能将外周血中多余的胆固醇带回肝脏代谢生成胆汁酸,Chemicalbook因此HDL升高是抗心肌梗死的安全因子。昆布多糖可使血浆中胆固醇含量减少13%~17%,低密度脂蛋白降低20%~25%,高密度脂蛋白含量增加16%,使动脉粥样硬化指数减少,血浆中脂质过氧化物浓度降低。昆布的不同溶剂提取物具有降低血脂的作用。在降血脂研究方面,昆布多糖通过改善血脂代谢,能有效防治动脉粥样硬化及其它心脑血管疾病的发生。
4.抗凝血作用褐藻多糖硫酸酯能增加动物出血量并延长出血时间,还能抑制大鼠动、静脉血栓的形成。对于凝血酶、CaCl2、花生四烯酸、二磷酸腺苷等诱导剂引起的血小板聚集均有抑制作用。
5.抗氧化作用褐藻多糖硫酸酯能够明显抑制细胞氧化溶血,对脂质过氧化具有很好的保护作用。
6.降血糖作用昆布多糖不仅能够降低糖尿病小鼠的血糖、参与糖代谢,且能调节糖尿病小鼠的蛋白质代谢,在降糖的同时促进胰岛细胞分泌胰岛素。
7.抗辐射作用褐藻酸钠对放射性元素54Mn、90Sr、109Cd、133Sn、133Ra有排除及阻止吸收的作用。还可降低被131I和137Cs辐射的大鼠恶性肿瘤及白血病的发病率。
8.抑菌、抗病毒作用昆布水煎液对狗小孢子菌、红色毛癣菌、孢子丝菌、石膏样毛癣菌、絮状表皮癣菌等均有一定抑制作用;昆布多糖能抗RNA和DNA病毒,抑制脊髓灰质炎病毒Ⅲ型、柯萨奇B3和A16型病毒、埃可病毒Ⅳ型等,还具有抗HIV病毒的作用。
9.保护作用昆布多糖对吸入性苯中毒有一定的保护作用,昆布多糖对苯中毒引起的小鼠骨髓抑制有一定的拮抗保护作用,其作用机制与其对机体的免疫调节和抗突变、抗氧化等功能有关。
10.其他作用昆布多糖尚具有降低血压、调节酪氨酸激酶活性、抗肺间质纤维化、抗突变、耐疲劳等多种生物活性。
本发明利用昆布多糖包裹氨基酸微粒,使其形成核壳结构,通过调节包裹物的浓度和包裹层的厚度来调节氨基酸在人体内的半衰期,提高氨基酸的利用率;在实际使用时,调节氨基酸微粒、一层核壳结构的氨基酸和三层核壳结构的氨基酸的比例,可以兼顾到氨基酸的及时补充和较长的缓释期,适用于所有需要补充氨基酸的人群。昆布多糖具有多种药理作用,其包裹氨基酸,既能解决氨基酸服用后半衰期短的问题,又符合中医药食同源的养生理念。
在本说明书的描述中,参考术语“一个实施例”、“示例”、“具体示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中,对上述术语的示意性表述不一定指的是相同的实施例或示例。而且,描述的具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。
最后需要说明的是,以上公开的本发明优选实施例只是用于帮助阐述本发明。优选实施例并没有详尽叙述所有的细节,也不限制该发明仅为所述的具体实施方式。显然,根据本说明书的内容,可作很多的修改和变化。本说明书选取并具体描述这些实施例,是为了更好地解释本发明的原理和实际应用,从而使所属技术领域技术人员能很好地理解和利用本发明。本发明仅受权利要求书及其全部范围和等效物的限制。
Claims (10)
1.一种核壳体缓释氨基酸补剂,其特征在于,其包括氨基酸内核和包裹在氨基酸内核外侧的一层或多层外壳,其中一层或多层外壳材料为昆布多糖。
2.根据权利要求1所述的一种核壳体缓释氨基酸补剂,其特征在于,所述核壳体缓释氨基酸补剂为一层核壳结构,包括氨基酸内核和包裹氨基酸内核的昆布多糖外壳。
3.根据权利要求1所述的一种核壳体缓释氨基酸补剂,其特征在于,所述核壳体缓释氨基酸补剂为三层核壳结构,包括氨基酸内核、包裹物为昆布多糖的第一层外壳、包裹物为淀粉的第二层外壳和包裹物为昆布多糖的第三层外壳。
4.根据权利要求3所述的一种核壳体缓释氨基酸补剂,其特征在于,所述第一层外壳的厚度小于第二层外壳,且第二层外壳的厚度小于第三层外壳。
5.根据权利要求1所述的一种核壳体缓释氨基酸补剂,其特征在于,所述氨基酸内核为氨基酸的环糊精包合物。
6.根据权利要求3所述的一种核壳体缓释氨基酸补剂的制备方法,其特征在于,包括以下步骤:
S1、低温条件下,将氨基酸进行超微粉碎,粉碎后过600-1000目筛,得到氨基酸微粒;
S2、将昆布多糖投入去离子水中,均质后,对氨基酸微粒进行包裹,得到一层结构包裹物;
S3、将S2产生的一层结构包裹物进行干燥处理,之后将水溶淀粉投入去离子水中,均质后,对一层结构包裹物进行二次包裹,得到二层结构包裹物;
S4、将S3产生的二层结构包裹物进行干燥处理,之后将昆布多糖投入去离子水中,均质后,对二层结构包裹物进行包裹,得到三层结构包裹物;
S5、将S4产生的三层包裹物进行干燥处理,得到三层外壳的核壳结构体缓释氨基酸补剂。
7.根据权利要求6所述的一种核壳体缓释氨基酸补剂的制备方法,其特征在于,S2、S3和S4中,包裹时采用超声波辅助,超声波频率50k-100kHz。
8.根据权利要求6所述的一种核壳体缓释氨基酸补剂的制备方法,其特征在于,S3、S4和S5中,烘干温度为75-90℃,时间为20-40min。
9.根据权利要求6所述的一种核壳体缓释氨基酸补剂的制备方法,其特征在于,S2中,昆布多糖与去离子水的重量比为(2-5):8;S4中,昆布多糖与去离子水的重量比为(4-6):8。
10.根据权利要求6所述的一种核壳体缓释氨基酸补剂的制备方法,其特征在于,S2、S4中,昆布多糖与去离子水均质时,温度为40-60℃。
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