CN115624179B - 一种耐酸、清除ros的微凝胶及制备和在载体的应用 - Google Patents
一种耐酸、清除ros的微凝胶及制备和在载体的应用 Download PDFInfo
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- CN115624179B CN115624179B CN202211273554.XA CN202211273554A CN115624179B CN 115624179 B CN115624179 B CN 115624179B CN 202211273554 A CN202211273554 A CN 202211273554A CN 115624179 B CN115624179 B CN 115624179B
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- microgel
- anthocyanin
- acid
- ros
- sodium alginate
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Abstract
本发明属于生物技术领域,涉及一种耐酸、清除ROS的微凝胶及制备和在载体的应用。本发明公开了一种耐酸、清除ROS的微凝胶,其组分包括:硒化魔芋葡甘聚糖、巯基化海藻酸钠和钙盐。该微凝胶具有自主ROS清除和耐酸型钙交联层确保的肠黏膜黏附性能。该微凝胶作为递送载体,能有效避免活性因子被胃酸降解和被胃肠道中ROS氧化失效,从而实现活性因子,例如营养素、益生菌或药物,稳定、高效肠靶向释放,对于提升其生物利用度意义重大,在功能食品与制药领域具有广阔的应用前景。
Description
技术领域
本发明属于生物技术领域,涉及一种耐酸、清除ROS的微凝胶及制备和在载体的应用。
背景技术
多酚是植物中常见的生物活性物质,具有抗炎、抗肿瘤、抗糖尿病等多种功效,在食品、医药、化妆品领域均有重要应用。然而,包括花青素、槲皮素、姜黄素等在内的大部分多酚的首过效应强、体内代谢迅速,更因易被胃肠道中大量ROS(reactive oxygenspecies)氧化成醌失效和被胃酸、酶降解等原因使其难以获得预期的作用效果,导致应用受限,生物利用度大大降低。为改善这一应用现状,目前大多载体(环糊精、固体分散体、微乳、纳米混悬液、脂质体、微球、微囊等)都难以实现多酚的精准靶向递送,尤其难以保证多酚在目标部位释放后其活性可继续保持。
硒化魔芋葡甘聚糖为魔芋葡甘聚糖与葡甘聚糖酶酶解后,经过亚硒酸钠反应得到的硒多糖。CN110526996A公开了一种硒化魔芋葡甘寡糖及其制备和应用,公开了硒化魔芋葡甘聚糖可以降低炎症因子IL-6的产生,具有抗炎活性;可促使肝癌细胞凋亡增加,从而发挥抗癌作用;具有良好的自由基清除效果;可使紫外线诱导的衰老细胞数降低,从而具有抗衰老潜能。
巯基化海藻酸钠为海藻酸钠与巯基乙醇酸复合得到的偶联物。CN102408496B公开了一种原位交联海藻酸钠水凝胶及其制备方法,公开了巯基化海藻酸钠水溶液经溶液中氧气氧化巯基交联形成二硫键交联得到的水凝胶具有pH敏感性和还原响应性。
基于活性因子的控释原理,肠靶向载体主要分为三类:第一类是基于上消化道和下消化道的pH差异构建的pH响应型载体,由于载体对胃肠道的pH响应是个较为缓慢的过程,易出现释放滞后的现象;第二类则期望通过载体与肠道中的电解质、黏液层等形成氢键、离子键等非共价键实现营养素的肠靶向递送,然而非共价作用易受到胃部的强酸性pH和温度影响,稳定性不可控,难以实现精准靶向递送;第三类是将含巯基的载体与肠黏膜黏蛋白中的巯基氧化形成二硫键实现营养素的肠靶向递送,但载体一经摄取首先与口腔、胃粘膜发生黏附,最终在肠道中的黏附型释放行为将大打折扣。
现阶段尚未见从构建可自主清除ROS的载体的角度提升多酚的递送稳定性的报道,也无通过ROS自主清除、耐酸肠靶向协同作用实现多酚的稳定高效肠靶向递送的相关报道。由此,发明人通过构建可自主清除ROS、耐酸肠靶向型活性因子载体,一方面通过载体的ROS自主清除功能避免活性因子被氧化失效,另一方面通过耐酸与肠黏膜黏附性能的协同作用实现活性因子的高效稳定肠靶向递送。
发明内容
本发明的目的在于提供可自主清除ROS、耐酸肠靶向型活性因子载体,一方面通过载体的ROS自主清除功能避免活性因子被氧化失效,另一方面通过耐酸与肠黏膜黏附性能的协同作用实现活性因子的高效稳定肠靶向递送。
基于上述目的,本申请通过提供一种耐酸、清除ROS的微凝胶及制备和在载体的应用来解决该领域中的这种需要。
一方面,本发明涉及一种微凝胶,其组分包括:硒化魔芋葡甘聚糖、巯基化海藻酸钠和钙盐。
进一步地,本发明提供的微凝胶中,以质量比计,硒化魔芋葡甘聚糖、巯基化海藻酸钠、钙盐的配比为0.1~0.8:0.5~1.2:0.5~2.0;所述硒化魔芋葡甘聚糖中硒含量为5.5g kg-1,所述巯基化海藻酸钠中巯基含量为584.4μg mol-1。
进一步地,本发明提供的微凝胶中,所述钙盐选自乳酸钙、氯化钙、碳酸钙中的一种;优选地,所述钙盐选为乳酸钙。
进一步地,本发明提供的微凝胶中,制备方法包括:将硒化魔芋葡甘聚糖和巯基化海藻酸钠在水中混合均匀得到硒化魔芋葡甘聚糖-巯基海藻酸钠混合液,所述硒化魔芋葡甘聚糖-巯基海藻酸钠混合液经钙盐交联1~12h即为所述微凝胶。
进一步地,本发明提供的微凝胶中,所述硒化魔芋葡甘聚糖-巯基海藻酸钠混合液中,所述硒化魔芋葡甘聚糖的质量分数为0.1~0.8%,所述巯基海藻酸钠的质量分数为0.5%~1.2%;优选地,所述硒化魔芋葡甘聚糖-巯基海藻酸钠混合液中,所述硒化魔芋葡甘聚糖与所述巯基海藻酸钠的质量分数之和为1.3%。
另一方面,本发明涉及一种微胶囊,其包括上述的微凝胶和活性物质,所述活性物质为营养素、益生菌或药物。
进一步地,本发明提供的微胶囊中,所述活性物质为营养素;所述营养素为多酚;所述多酚选自花青素、姜黄素、槲皮素、虾青素中的一种。
本发明所声明的活性物质是指对生命现象具有影响的微量或少量的物质,包括多糖、萜类、甾醇类、生物碱、肽类、核酸、蛋白质、氨基酸、甙类、油脂、蜡、树脂类、植物色素、矿物质元素、酶和维生素等,也包括对生命现象具有影响的药物。
进一步地,本发明提供的微胶囊中,所述多酚为花青素,所述微胶囊粒径小于200nm。
营养素(nutrient)为维持机体繁殖、生长发育和生存等一切生命活动和过程,需要从外界环境中摄取的物质,多酚为营养素中的一种。但营养素大多首过效应强、体内代谢迅速,更因易被胃肠道中大量ROS氧化成醌失效和被胃酸、酶降解等原因使其难以获得预期的作用效果,导致作为食品直接服用时效果不佳,生物利用度大大降低。本发明提供了一种微凝胶,其作为营养素的载体时,能避免营养素被胃酸侵蚀以及ROS氧化失效,通过耐酸与肠黏膜黏附性能的协同作用实现营养素的高效稳定肠靶向递送。由此,本发明进一步请求保护一种肠靶向功能食品,其选用上述的微凝胶作为食品载体。
口服结肠定位给药系统是经口服途径将药物传递到结肠定位释放的一类药物制剂。给药后药物在胃及小肠内不释放,当转运至结肠时才崩解或溶蚀,使释放的药物在结肠病灶部位浓集,且结肠因其稳定的环境和高密度的酶活性及接近中性的pH,适于药物吸收。药物在结肠的驻留时间较长,也有利于长效药物系统发挥作用,可用于治疗结肠炎、结肠癌等局部性肠道疾病,还可通过延迟释药方法,用于治疗生理节律性疾病。本发明提供了一种微凝胶,其作为药物的载体时,能避免药物活性成分被胃酸侵蚀以及ROS氧化失效,通过耐酸与肠黏膜黏附性能的协同作用实现药物活性成分的高效稳定肠靶向递送。由此,本发明进一步请求保护一种肠靶向药物,其选用上述的微凝胶作为药物活性成分载体。
本发明提供了一种微凝胶,其自身具备良好的清除ROS作用,作为载体尤其适用于易被ROS氧化失效的药物。由此本发明进一步请求保护一种用于清除ROS的药物载体,其有效成分包含上述的微凝胶。
另一方面,本发明涉及上述微凝胶在制备肠靶向功能食品中的应用。
另一方面,本发明涉及上述微凝胶在制备肠靶向药物中的应用。
本发明与现有技术相比具有以下有益效果或者优点:
本发明提供的微凝胶,具有ROS自主清除、耐酸肠靶向性。将活性物质包埋于微凝胶中,可有效避免活性物质被胃酸、酶和胃肠道ROS降解,保持活性物质的生物活性,实现稳定高效肠靶向递送,并能有效提升活性物质的生物利用度。本发明提供的微凝胶,带负电且其结构中含有相当数量的巯基,既能与肠黏液黏蛋白形成二硫键产生肠黏液黏附力,更能与带负电荷的肠道黏液产生微弱的静电斥力,从而赋予微凝胶黏液黏附性和一定的黏液渗透性。本发明提供的微凝胶对·DPPH、·OH、·ABTS此类ROS表现出显著的清除效果。本发明提供的一种微胶囊,其采用本发明提供的微凝胶与多酚复合制得,本发明提供的微凝胶作为多酚的载体,在提升其稳定性的同时,有助于发挥其抗氧化活性。
附图说明
图1为海藻酸钠(a)、巯基海藻酸钠(b)、魔芋葡甘聚糖(c)、硒化魔芋葡甘聚糖(d)、微凝胶(e)、花青素(f)、微凝胶@花青素(g)的红外光谱图。
图2为微凝胶(A)、微凝胶@花青素(B)、模拟胃液处理2h(C)、模拟肠液处理2h(D)和4h(E)后微凝胶@花青素的透射电子显微镜图片。
图3为微凝胶(a)、微凝胶@花青素(b)的粒径分布曲线。
图4为巯基海藻酸钠、硒化魔芋葡甘聚糖、微凝胶、花青素、微凝胶@花青素的Zeta电位。
图5为经模拟胃肠液处理的花青素、硒化魔芋葡甘聚糖、乳酸钙交联巯基海藻酸钠微凝胶、乳酸钙交联海藻酸钠微凝胶、负载花青素的乳酸钙交联巯基海藻酸钠微凝胶、微凝胶、微凝胶@花青素的DPPH·、OH·、ABTS·、·O2-自由基清除活性。
图6为经模拟胃肠液处理的花青素、乳酸钙交联海藻酸钠-硒化魔芋葡甘聚糖微凝胶、微凝胶、微凝胶@花青素在pH2.0、5.0和7.0对黏蛋白的黏附性能。
图7为微凝胶@花青素的粒径及Zeta电位-时间曲线。
图8为微凝胶@花青素在模拟胃、十二指肠、小肠液环境下的释放曲线图。
图9为花青素和微凝胶@花青素的体外生物利用度。
具体实施方式
下面,结合实施例对本发明的技术方案进行说明,但是,本发明并不限于下述的实施例。
为了使本领域技术人员更好地理解本发明的技术方案能予以实施,下面结合具体实施例和附图对本发明作进一步说明,但所举实施例不作为对本发明的限定。
下述各实施例中所述实验方法和检测方法,如无特殊说明,均为常规方法;所述试剂和材料,如无特殊说明,均可在市场上购买得到。
实施例1
本实施例提供了一种微凝胶及其制备的微胶囊。
本实施例意图说明海藻酸钠、巯基海藻酸钠、魔芋葡甘聚糖、硒化魔芋葡甘聚糖、微凝胶、花青素、微凝胶@花青素的制备过程与实质区别。
在该实施例中,按照下列方式制备的乳酸钙交联硒化魔芋葡甘聚糖-巯基海藻酸钠微凝胶载体,简称微凝胶;乳酸钙交联硒化魔芋葡甘聚糖-巯基海藻酸钠负载有代表性多酚营养素中的花青素,简称微凝胶@花青素。
称取0.50g魔芋葡甘聚糖加入50mL 0.5%(v/v)硝酸溶液中,充分混合后向混合液中加入0.86g亚硒酸钠和0.61g氯化钡,搅拌溶解60℃反应9h,结束后将体系冷至室温;再向其中加入0.50g无水硫酸钠搅拌均匀,产生白色沉淀;离心后收集上清液并向其中加入碳酸氢钠将pH调至中性,再缓慢加入足量乙醇并不断搅拌产生白色沉淀,离心后收集沉淀物50℃下真空干燥3h,获得硒化魔芋葡甘聚糖。
将1.00g海藻酸钠溶于20mL去离子水中,先后向溶液中缓慢加入1.30mL巯基乙醇酸和1mL、10M的盐酸,60℃反应3h后将冷至室温的反应液缓慢加入足量甲醇产生白色沉淀,收集沉淀物室温真空干燥即为巯基海藻酸钠。
将1mL、质量分数为0.65%的硒化魔芋葡甘聚糖水溶液与3.5mL、质量分数为0.65%的巯基海藻酸钠水溶液均匀混合,并将混合液置于室温下搅拌12h后再逐滴加入12mL、1%的乳酸钙溶液中,滴加完毕后室温下搅拌5h,获得微凝胶。冷冻干燥后避光保存备用。
取1mL、20mg mL-1蓝莓花青素水溶液与3.5mL、质量分数为0.65%的硒化魔芋葡甘聚糖水溶液搅拌混合均匀,再加入1mL、质量分数为0.65%巯基海藻酸钠水溶液中混合均匀,室温搅拌过夜再逐滴加入12mL、1%的乳酸钙溶液中,滴加完毕后室温下搅拌5h,获得微凝胶@花青素,冷冻干燥后避光保存备用。
如图1(a)所示的海藻酸钠的红外光谱图中,除了2900~3100、1650~1740、1400cm-1处代表-COOH中-OH、和-OH以及-C=O的面内弯曲振动,尤其在巯基化后在2668cm-1处出现了巯基特征峰,表明巯基海藻酸钠已形成(图1(b));魔芋葡甘聚糖的红外光谱中-C-O-C-伸缩振动、-C-H伸缩振动、乙酰-C=O和-OH伸缩振动分别出现在1024、2928、1734和3300cm-1(图1(c)),在硒化后753cm-1出现了亚硒酸酯的特征峰,说明硒化魔芋葡甘聚糖的形成(图1(d));经过乳酸钙交联,微凝胶的红外谱图中2895、2983cm-1处-C-H键的对称和非对称伸缩振动峰强度不仅变弱,且未见-C=O和巯基的特征峰。总的来讲,1734~1130cm-1区域内的峰均向低波数移动,所有吸收峰的强度变宽变弱,这归因于钙离子交联海藻酸钠中羧基形成蛋壳状结构所致,即G段开始折叠堆积形成褶皱,使规整的结构变为缠绕的交联结构,最终形成一个三维网状结构。由于空间效应,所有吸收峰的强度减弱和一些吸收峰都向低波数移动,甚至有些峰在交联后消失,这都是因为乳酸钙交联后形成的海藻酸钙层限制了花青素的空间取代行为,从而使得特征吸收峰消失或者向低波数移动,这说明微凝胶@花青素已成功制备(图1(e-f))。
实施例2
本实施例提供了硒化魔芋葡甘聚糖中硒含量的测定和巯基海藻酸钠中巯基含量测定。
硒化魔芋葡甘聚糖中硒含量的测定:称取实施例1制备的硒化魔芋葡甘聚糖,加入浓硝酸,在100℃的密闭消化罐中消化4h,以1%超纯硝酸稀释定容,用电感耦合等离子体质谱测定其硒含量。
巯基海藻酸钠中巯基含量测定:称取实施例1制备的巯基海藻酸钠(1mg)加入0.5mL Ellman's缓冲液(0.5M磷酸盐缓冲液pH 8.0)酸化,再加入0.5mL Ellman试剂(3毫克5,50-二硫代(2-硝基苯甲酸)加入10mL埃尔曼缓冲液,pH 8.0)。混合液室温孵育3h后测定混合液在450nm的吸光度。巯基接枝百分率根据L-半胱氨酸标准曲线计算。
据测定,所制备的硒化魔芋葡甘聚糖中硒含量为5.5g kg-1,巯基海藻酸钠中巯基含量为584.4μmol g-1。
实施例3
本实施例提供了模拟胃液、肠液处理试验。
本实施例意图说明微凝胶的耐酸能力,微凝胶作为载体能有效保护活性因子不被胃酸破坏,以及微凝胶的肠靶向能力。
将实施例1制备的微凝胶、微凝胶@花青素及模拟胃液、肠液处理的微凝胶@花青素分散于去离子水后,滴加至铜网上通过透射电子显微镜观察其形貌。
微凝胶和微凝胶@花青素的粒径均小于200nm,且后者粒径略大于前者,说明花青素已被成功负载。在此粒径下的纳米颗粒可顺利穿透肠道黏液层,能有效避免因黏液层包裹阻碍微凝胶扩散和其中花青素的释放,即便释放的花青素也难被肠道上皮细胞吸收,从而有助于提高生物利用度。如图2(A)所示,微凝胶是粒径为101.39±15.66nm的球状结构。如图2(B)所示,在负载花青素后得到的微凝胶@花青素的增大至160.41±23.36nm。如图2(C)所示,经过模拟胃液处理,微凝胶表面未见显著的破坏,说明能在保护其中的花青素不被胃酸破坏。如图2(D)与图2(E)所示,随着经过模拟肠液处理时间的延长,微凝胶@花青素形貌的破坏程度与处理时间成正比,原本的球状结构被破坏后形成了摊开甚至是堆叠的凝胶碎片以及释放的花青素纳米颗粒,说明钙交联层经过模拟肠液的消化/发酵作用,本发明提供的微凝胶作为载体,可以确保花青素肠靶向释放。
综合上述实验结果可知,将花青素包埋于本发明提供微凝胶中,可有效避免花青素被胃酸、酶和胃肠道ROS降解,保持花青素的生物活性,实现稳定高效肠靶向递送。本领域内技术人员易于知晓,将活性因子,例如营养素、益生菌或药物,作为有效成分包裹于本发明提供微凝胶中,也能取得近似的效果。
实施例4
本实施例提供了实施例1制备的微凝胶、微凝胶@花青素的粒径及其分布、Zeta电位。
采用动态光散射激光粒度Zeta电位仪测定实施例1制备的微凝胶、微凝胶@花青素的粒径及其分布、Zeta电位。
如图3所示,微凝胶的粒径为304.1±4.5nm,多分散指数PDI为0.331±0.012;微凝胶@花青素的粒径为406.6±13.2nm,多分散指数PDI为0.383±0.021。
在图4中,花青素几乎不带电,巯基海藻酸钠的电位是-22.3mV,硒化魔芋葡甘聚糖带负电,为-10.8mV,经过乳酸钙交联后微凝胶依然带负电(-30.1mV),在花青素负载后,花青素负载微凝胶的Zeta电位为-33.2mV。
实施例5
本实施例提供了实施例1制备的微凝胶的载药效果。
本实施例意图说明微凝胶作为药物或活性因子载体时的载药效果。
取适量微凝胶@花青素冻干粉末分散于3mL pH 7.4 PBS中,搅拌24h,将混合物在冰浴中超声处理10min。离心混合液,并通过紫外可见分光光度计在520nm处测量上清液吸光度,代入标准曲线计算上清液中花青素的质量。根据下式计算微凝胶的载药量(%):
据测定,微凝胶载药量为9.97%,包封率为66.44%。
实施例6
本实施例提供了微凝胶与微凝胶@花青素的抗氧化活性。
本实施例研究微凝胶、微凝胶@花青素对DPPH·、ABTS·+、OH·、·O2-自由基清除活性,以此反映微凝胶的抗氧化活性。其中,花青素、硒化魔芋葡甘聚糖、乳酸钙交联巯基海藻酸钠微凝胶、乳酸钙交联海藻酸钠微凝胶、负载花青素的乳酸钙交联巯基海藻酸钠微凝胶作为对照样,所有样品在进行抗氧化试验前均经过模拟胃肠液处理。未经过模拟胃肠液处理的抗坏血酸(Vc)作为阳性对照。
乳酸钙交联巯基化海藻酸钠:1mL 0.3%巯基化海藻酸钠(TSA)逐滴滴加到6mL1%乳酸钙溶液中,滴加完成后继续搅拌5h,离心取上清液,冷冻干燥。
钙离子交联海藻酸钠微凝胶:1mL 0.3%海藻酸钠(SA)逐滴滴加到6mL 1%乳酸钙溶液中,滴加完成后继续搅拌5h,离心取上清液,冷冻干燥。
负载花青素的乳酸钙交联巯基化海藻酸钠微凝胶:1mL花青素溶液(20mg/mL)与3.5mL 0.3%巯基化海藻酸钠(TSA)混合后搅拌过夜。取上述混合溶液1mL,逐滴滴加到6mL1%乳酸钙溶液中,滴加完成后继续搅拌5h,离心取上清液,冷冻干燥。
试验过程:用于自由基清除的所有样品(除Vc外)经过模拟胃液37℃处理2h。随后用1M NaOH调节上述模拟胃液的pH值约为7.0,再加入等量胰蛋白酶37℃孵育4h。结束后将所有样品冷冻干燥,得到粉末状样品用于各项自由基清除实验,试验样与对照样的试验条件相同,各组样品试验有效成分成分浓度均为2mg mL-1,每组试验重复3次,具体试验结果见图5。
如图5所示,花青素对·DPPH、·OH的清除率分别为21.22±1.21%、42.18±0.28%,对·O2 -不具有清除效果。微凝胶对·DPPH、·OH、·ABTS表现出显著的清除效果,说明本专利所提供的微凝胶对于自由基的清除能力具有普适性。如图5所示,微凝胶@花青素对于·DPPH、·OH和·O2 -的清除效率分别高达96.49±0.24%、64.36±0.65%和20.97±0.24%。将微凝胶负债花青素后得到的微胶囊甚至可使微凝胶的自主清除能力有大幅提升,这一方面是由于微凝胶和花青素两者的协同作用使得自由基自主清除效果大大改善,另一方面也意味着所述微凝胶载体能保护花青素免于被胃酸、ROS破坏,在提升其稳定性的同时有助于发挥固有的抗氧化活性。
事实上,在胃肠道中活性氧往往是较多的,且在不同器官中形成活性氧的机制不同。由于还原辅酶II和氧化酶在细胞膜、线粒体、过氧化物酶体和内质网中广泛存在,此外线粒体内膜的电子传递链还会产生一定量的ROS。同时,某些物质和病原体的摄入可刺激上皮细胞、多态核中性粒细胞、巨噬细胞等炎症介质分泌炎症因子等炎症介质,促进氧化应激的发生。因此,本专利提供的微凝胶和微凝胶@花青素在肠道炎症的治疗方面有着潜在的应用价值。
实施例7
本实施例提供了微凝胶@花青素对黏蛋白的吸附性能。
采用高碘酸席夫(PAS)比色法定量测定花青素、乳酸钙交联海藻酸钠-硒化魔芋葡甘聚糖微凝胶、微凝胶、微凝胶@花青素对黏蛋白吸附性能。
如图6所示,在pH 2.0、5.0和7.0的条件下,通过对黏蛋白的体外黏附来评估花青素、微凝胶和微凝胶@花青素的黏附行为,以乳酸钙交联海藻酸钠-硒化魔芋葡甘聚糖微凝胶作为对照。在pH 2.0时,花青素和对照微凝胶对黏蛋白具有最大吸附量,微凝胶和微凝胶@花青素的最大吸附量出现在pH 7.0。由于黏蛋白中大量的唾液酸、磺酸基和羧基在pH2.0仍保持质子化,黏液黏附性源于花青素、对照微凝胶与黏蛋白之间的弱氢键作用以及硒化魔芋葡甘聚糖中有限的-CH2段、对照微凝胶表面的海藻酸钠与黏蛋白-CH3基团之间的范德华相互作用。pH 2.0时,微凝胶和微凝胶@花青素对黏蛋白的黏附能力与花青素、对照微凝胶相当,这是因为在该条件下微凝胶的形态几乎没有变化,钙交联层遮盖了与微凝胶中可与黏蛋白结合的几乎所有位点。所述载体的有效成分之一为巯基海藻酸钠,经过乳酸钙交联形成的钙交联层可使巯基在口腔、胃中不致暴露,避免载体与口腔、胃黏膜黏附。在pH5.0时,黏蛋白中-SO3 -、-COO-(>pKa为2.6)下均带负电荷,带负电的对照微凝胶与黏蛋白存在静电斥力,导致对照微凝胶的黏附性能下降。微凝胶@花青素在pH 7.0时对黏蛋白的黏附效率是游离花青素的~32倍,是对照微凝胶对黏蛋白黏附效率的~28倍,这种优异的黏附特性是因为海藻酸钙微凝胶在下消化道消化/发酵后导致其形态的被彻底破坏、引起巯基海藻酸钠和硒化魔芋葡甘聚糖碎片链段的产生和花青素的逐渐释放,因此与黏蛋白的黏附更加牢固,结果表明花青素的释放量与微凝胶的形态破坏和黏附效率成正比,更说明微凝胶能有效提高花青素的生物利用度。
将微凝胶@花青素冻干粉末复溶于去离子水,一月内定期监测其粒径、Zeta电位随时间的变化。
如图7所示,在一个月内粒径和Zeta电位几乎无显著变化,说明微凝胶的稳定性良好。
实施例8
本实施例提供了微凝胶@花青素的肠靶向释放。
研究微凝胶@花青素在pH 1.2、5.0和7.2的PBS中的释放情况。首先将3mg的样品加入到1ml PBS缓冲溶液(pH=1.2)中,37℃、100rpm下持续搅拌2h后,用NaOH调节pH至5.0,继续在37℃,100rpm下搅拌1h后继续用NaOH调节pH至7.2,持续搅拌2h,定期取样并在520nm处测量吸光度,计算花青素在各个阶段的累积释放量。每次取样时补充同体积同pH磷酸盐缓冲液。
如图8所示,微凝胶@花青素的体外释放曲线在模拟胃液(pH 1.2)的释放量约为7.90%,在模拟十二指肠液(pH 7.2)的条件下,花青素释放量为10.36%,最后在模拟小肠液中花青素的累积释放量为85.96%。说明微凝胶的钙交联层可以有效保护花青素免受胃酸破坏,随着海藻酸钙交联层在下消化道的逐步消化/发酵,实现花青素的肠靶向释放。
实施例9
本实施例提供了微凝胶@花青素的体外生物利用度试验。
本发明意图说明微凝胶对活性因子生物利用度的提升作用。
采用体外消化法研究花青素和微凝胶@花青素的体外生物利用度。在体外消化后,取消化液在4℃、以12000g的转速离心45min,用酶标仪测定上清液吸光度,根据如下公式计算体外生物利用度:体外生物利用度(%)=(消化后微凝胶中花青素浓度/消化液中花青素浓度)×100%。
参见图9,在体外消化后花青素的体外生物利用度为52.89±1.12%。在模拟肠液中,随着微凝胶的海藻酸钙交联层不断被消化,花青素释放至上清液中可被检测,微凝胶@花青素的体外生物利用度提升至81.19±5.51%。结合微凝胶在胃肠道的形貌变化、黏附作用及最终赋予花青素肠靶向释放行为的结果说明,在微凝胶的保护作用下,花青素可免于被胃酸和胃肠道中的大量ROS降解失效,该载体能大大提升花青素的生物利用度。
如上所述,即可较好地实现本发明,上述的实施例仅仅是对本发明的优选实施方式进行描述,并非对本发明的范围进行限定,在不脱离本发明设计精神的前提下,本领域普通技术人员对本发明的技术方案做出的各种改变和改进,均应落入本发明确定的保护范围内。
Claims (3)
1.一种微凝胶,其特征在于,组分包括:硒化魔芋葡甘聚糖、巯基海藻酸钠和乳酸钙;
所述硒化魔芋葡甘聚糖的制备方法为:每0.50 g魔芋葡甘聚糖加入50mL 0.5% v/v硝酸溶液中,充分混合后向混合液中加入0.86 g亚硒酸钠和0.61 g氯化钡,搅拌溶解60℃反应9 h,结束后将体系冷至室温;再向其中加入0.50 g无水硫酸钠搅拌均匀,产生白色沉淀;离心后收集上清液并向其中加入碳酸氢钠将pH调至中性,再缓慢加入足量乙醇并不断搅拌产生白色沉淀,离心后收集沉淀物50 ℃下真空干燥3 h,获得硒化魔芋葡甘聚糖;
所述巯基海藻酸钠的制备方法为:每1.00 g海藻酸钠溶于20 mL去离子水中,先后向溶液中缓慢加入1.30 mL巯基乙醇酸和1 mL 10 M盐酸,60℃反应3h后将冷至室温的反应液缓慢加入足量甲醇产生白色沉淀,收集沉淀物室温真空干燥即为巯基海藻酸钠;
所述微凝胶的制备方法包括:将硒化魔芋葡甘聚糖和巯基海藻酸钠在水中混合均匀得到硒化魔芋葡甘聚糖-巯基海藻酸钠混合液,所述硒化魔芋葡甘聚糖-巯基海藻酸钠混合液经乳酸钙交联1~12h即为所述微凝胶;
所述硒化魔芋葡甘聚糖-巯基海藻酸钠混合液中,所述硒化魔芋葡甘聚糖的质量分数为0.1~0.8%,所述巯基海藻酸钠的质量分数为0.5%~1.2%。
2.一种微胶囊,其特征在于,包括权利要求1所述的微凝胶和活性物质;
所述活性物质为花青素。
3.权利要求1所述的微凝胶在制备肠靶向功能食品或药物中的应用,其特征在于,所述微凝胶作为所述肠靶向功能食品或药物的载体。
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1554330A (zh) * | 2003-12-22 | 2004-12-15 | 天津大学 | 用于载药的魔芋葡甘聚糖-海藻酸钙微球及制备方法 |
CN1560088A (zh) * | 2004-02-26 | 2005-01-05 | 彭祚全 | 一种硒化葡甘聚糖的制备方法 |
CN106867425A (zh) * | 2017-03-01 | 2017-06-20 | 福建农林大学 | 一种魔芋葡甘聚糖无痕可重复使用春联胶水及其制备方法 |
CN109464424A (zh) * | 2018-12-25 | 2019-03-15 | 四川大学 | 一种肠道给药载体巯基化海藻酸钙微球及其制备方法 |
CN113663122A (zh) * | 2021-08-24 | 2021-11-19 | 陕西科技大学 | 一种抗炎、抗菌、抗肿瘤的多功能水凝胶材料及其制备方法和应用 |
CN114053247A (zh) * | 2021-12-31 | 2022-02-18 | 西南大学 | 一种魔芋葡甘聚糖靶向递送胶囊及其制备方法 |
WO2022142448A1 (zh) * | 2020-12-29 | 2022-07-07 | 江南大学 | 一种负载外泌体的口服结肠靶向给药的聚合物的制备方法 |
-
2022
- 2022-10-18 CN CN202211273554.XA patent/CN115624179B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1554330A (zh) * | 2003-12-22 | 2004-12-15 | 天津大学 | 用于载药的魔芋葡甘聚糖-海藻酸钙微球及制备方法 |
CN1560088A (zh) * | 2004-02-26 | 2005-01-05 | 彭祚全 | 一种硒化葡甘聚糖的制备方法 |
CN106867425A (zh) * | 2017-03-01 | 2017-06-20 | 福建农林大学 | 一种魔芋葡甘聚糖无痕可重复使用春联胶水及其制备方法 |
CN109464424A (zh) * | 2018-12-25 | 2019-03-15 | 四川大学 | 一种肠道给药载体巯基化海藻酸钙微球及其制备方法 |
WO2022142448A1 (zh) * | 2020-12-29 | 2022-07-07 | 江南大学 | 一种负载外泌体的口服结肠靶向给药的聚合物的制备方法 |
CN113663122A (zh) * | 2021-08-24 | 2021-11-19 | 陕西科技大学 | 一种抗炎、抗菌、抗肿瘤的多功能水凝胶材料及其制备方法和应用 |
CN114053247A (zh) * | 2021-12-31 | 2022-02-18 | 西南大学 | 一种魔芋葡甘聚糖靶向递送胶囊及其制备方法 |
Non-Patent Citations (2)
Title |
---|
"硒化魔芋葡甘寡糖的合成及其抗氧化活性";刘启顺等;《食品科学》;全文 * |
"黏膜给药中的黏液屏障及相关递送策略研究进展";吕风梅等;《药学学报》;全文 * |
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