CN114948910A - 一种小肠靶向释放的板栗壳多酚缓释材料及其制备和应用 - Google Patents
一种小肠靶向释放的板栗壳多酚缓释材料及其制备和应用 Download PDFInfo
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- CN114948910A CN114948910A CN202210720629.8A CN202210720629A CN114948910A CN 114948910 A CN114948910 A CN 114948910A CN 202210720629 A CN202210720629 A CN 202210720629A CN 114948910 A CN114948910 A CN 114948910A
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- chestnut shell
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- shell polyphenol
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Abstract
本发明公开了一种小肠靶向释放的板栗壳多酚缓释材料及其制备和应用，该缓释材料包括介孔二氧化硅纳米颗粒以及负载于介孔二氧化硅纳米颗粒内的板栗壳多酚，介孔二氧化硅纳米颗粒以正硅酸四乙酯、十六烷基三甲基溴化铵和无机铵盐为原料并通过气溶胶法制备得到，板栗壳多酚通过浸渍法负载于其中。该缓释材料显著提高了板栗壳多酚在小肠吸收部位的释放量，避免在消化过程中过早释放而降低了小肠吸收效率，进而提高了板栗壳多酚的生物利用率。
Description
技术领域
本发明属于缓释材料技术领域，具体涉及一种小肠靶向释放的板栗壳多酚缓释材料及其制备方法，以及其在食品或药物制备中的应用。
背景技术
作为板栗加工副产物，板栗壳含有丰富的多酚化合物，故板栗壳可以成为一种廉价和容易获得的多酚化合物来源。目前对于膳食多酚的摄入主要通过口服，然而发明人在研究中发现：板栗壳提取物(Chestnut shell extracts，CSE)经过体外模拟胃消化后，板栗壳提取物的总酚含量、抗氧化能力上升；而经过体外模拟肠消化后，总酚含量、抗氧化能力下降在。表明酚类物质在胃肠消化道中的代谢会影响其在体内的生物利用率。多酚类物质在消化过程中，其结构易被破坏，生物活性和生物利用率均会降低。这是由于在经口腔摄入后，消化液中的酸碱度和消化酶会破坏其结构稳定性。而多酚化合物主要被小肠上皮细胞吸收，一旦进入消化道就会过早破坏多酚结构，从而降低其在机体内的抗氧化活性和生物利用率。因此，能够将板栗壳提取物靶向递送至小肠的递送载体是提高板栗壳提取物应用价值的关键。
目前，递送抗氧化活性物质可以采用纳米载体运载技术，且该技术已经取得了一定的进展，如Gadkari等将儿茶素封装在纳米脂质乳中进行输送，有效地提高了口服儿茶素的吸收效率，但是脂质类纳米载体稳定性不够且负载量有限。由于多酚类抗氧化活性物质对光、热、氧气、pH值和酶等极为敏感，而纳米载体颗粒因具有更高的稳定性和负载量引起了广泛关注，这类载体颗粒包括纳米管、聚合物纳米球以及介孔二氧化硅纳米颗粒(Mesoporous silica nanoparticles，MSNs)等。其中MSNs可通过二氧化硅/表面活性剂自组装精确控制颗粒孔径、结构、表面化学特性以及粒径来调节其释放特征，实现可控释放，大大提高被负载物的稳定性。
MSNs负载体系制备及其体外控释技术已有报道，但较少的研究关注其在胃肠消化液中结构是否保持完整，也没有研究报道负载板栗壳多酚的MSNs复合纳米颗粒在胃肠道环境中的释放情况及其对被负载物在机体中生物活性的影响，这些问题极大的影响了MSNs作为载体运用在食品和药物行业中。
发明内容
有鉴于此，本发明的目的在于提供一种小肠靶向释放的板栗壳多酚缓释材料，其能选择性在小肠靶向大量释放板栗壳多酚，避免消化液对板栗壳多酚活性的影响，进而提高了板栗壳多酚的利用率。
为了实现上述目的，本发明的技术方案具体如下：
一种小肠靶向释放的板栗壳多酚缓释材料，包括介孔二氧化硅纳米颗粒以及负载于介孔二氧化硅纳米颗粒内的板栗壳多酚。
进一步地，在上述技术方案中，介孔二氧化硅纳米颗粒的粒径为400～800nm，且孔径为1.8～6nm。
进一步地，在上述技术方案中，板栗壳多酚为乙醇浸提板栗壳所得。
进一步地，在上述技术方案中，介孔二氧化硅纳米颗粒的制备包括以下步骤：
S1、在溶剂中加入正硅酸四乙酯、十六烷基三甲基溴化铵和无机铵盐并混合均匀，加入水搅拌得到浑浊溶液，然后加入浓盐酸作为催化剂使溶液澄清；
S2、将澄清溶液雾化成气溶胶液滴，并于氮气环境下干燥液滴得到固体颗粒，煅烧后即得。
更进一步地，正硅酸四乙酯、十六烷基三甲基溴化铵和无机铵盐的质量比为5：(2～3)：(2～3)。
更进一步地，步骤S1中的溶剂为水或有机溶剂，其中有机溶剂为醇类、醚类或酯类，具体可以为甲醇、乙醇、丙酮或乙酸乙酯等。
更进一步地，无机铵盐为氯化铵或硫酸铵。
更进一步地，步骤2中液滴的干燥温度为350～450℃，煅烧温度为450～550℃。
本发明还提供了上述板栗壳多酚缓释材料的制备方法：将板栗壳多酚溶于无水乙醇，加入介孔二氧化硅纳米颗粒后超声分散，搅拌后降温浸渍(可根据实际需要重复多次)，离心后洗涤干燥沉淀即得。
本发明制备的板栗壳多酚缓释材料可用于制备药品或食品，以提高食品或药品中板栗壳多酚的生物利用率。
与现有技术相比，本发明的有益效果为：本发明通过气溶胶法制得MSNs作为载体，并采用浸渍法将板栗壳多酚负载进MSNs中形成缓释材料；该缓释材料能在胃消化环境中保持较稳定的结构，使得板栗壳多酚缓慢释放；但在肠液环境中其结构被破坏，从而大量释放板栗壳多酚，实现小肠靶向释放，提高了板栗壳多酚在生物体内的利用率；本发明通过调节十六烷基三甲基溴化铵(CTAB)和无机铵盐用量，可以控制二氧化硅纳米颗粒的表面形貌、比表面积、孔径、孔容以及负载多酚物质的靶向释放。
附图说明
图1为实施例1制备的MSNs(a)与CSE-MSNs(b)的透射电镜图；
图2为实施例1制备的MSNs、CSE-MSNs与CSE的红外吸收光谱对比图；
图3为实施例1制备的MSNs、CSE-MSNs与CSE的DSC曲线对比图。
具体实施方式
为了更好地理解本发明，下面结合具体实施例进一步阐明本发明的内容。应当理解的是，此处所描述的具体实施方式仅用于说明和解释本发明，并不用于限制本发明。
实施例1
本实施例提供了一种负载板栗壳多酚的缓释材料，其制备工艺如下：
(1)称取10g正硅酸四乙酯(TEOS)加入43ml无水乙醇搅拌均匀，再分别加入4.0gCTAB和4.0g NH4Cl，最后加入56ml超纯水，搅拌均匀后得到白色浑浊液体。然后加入0.5ml浓盐酸作为催化剂，溶液由浑浊逐渐变澄清透明后，静置1h。
(2)将澄清液倒入雾化气溶胶发生器中，使气溶胶液滴生成，并充入氮气使气溶胶液滴被干燥凝固在管式炉中(保持425℃)，收集得到白色颗粒。将其置于马弗炉中500℃煅烧5h，即得介孔二氧化硅纳米颗粒(MSNs)。
(3)自湖北罗田采得板栗原料，手工去壳洗净后放入干燥箱中50℃烘干，人工剥去内壳(囊衣)并收集起来。将烘干后的板栗壳用粉碎机多次粉碎后过60目筛，分别称取12.0g板栗壳和囊衣于500mL具塞锥形瓶中，加入70％乙醇(v/v)180mL，置于水浴锅中浸提90min，重复上述过程两次，合并滤液，干燥除溶剂即得CSE。
(4)称取0.025g步骤(3)制备的CSE溶于5ml无水乙醇中，加入0.1g MSNs，超声分散3min；用磁力搅拌器在30℃条件下搅拌0.5h，再置于4℃浸渍0.5h，此为一次变温处理，重复两次；于6000r/min离心10min，将沉淀用无水乙醇洗涤并离心，烘干后得到的缓释材料记作CSE-MSNs。
采用透射电镜对MSNs和CSE-MSNs进行检测，具体如图1所示：制备的纳米粒呈圆球状，有较为明显的孔道结构和空腔结构；负载CSE的MSNs外形呈规则、完整的球状，空腔明显变小，说明CSE已进入MSNs孔道中。
图2为CSE、MSNs和CSE-MSNs的红外吸收光谱对比，从图可知：在CSE-MSNs的红外光谱中，没有产生新的官能团，说明CSE和MSNs之间未发生化学反应产生新的化学键，而是通过各种物理作用力结合。
图3为CSE、MSNs和CSE-MSNs的DSC分析对比，从图中可知：说明CSE被成功的包裹在MSNs中并以非晶态形式或无定型态存在，没有结晶在硅球表面。
由于板栗壳提取物中酚类组分种类太多且纯度低，根据代谢物定性定量分析，选择其中含量较高的6种标准品(表儿茶素、儿茶素、表没食子酸儿茶素、芸香叶苷、表没食子儿茶素没食子酸酯及槲皮素)来研究其在体外消化过程中的稳定性，人工胃肠液对不同的单体化合物的稳定性不同，通过高效液相检测到表没食子儿茶素没食子酸酯(EGCG)在胃肠消化中稳定性最差，故选择EGCG进行MSNs复合体制备和在体外胃肠消化液中的释放表征。
实施例2
与实施例1不同的是，步骤(3)中的多酚物质为EGCG。本实施例所得缓释材料记为EGCG-MSNs-a。
实施例3
与实施例2不同的是，步骤(1)中采用硫酸铵替代氯化铵且加入量同样为4.0g。本实施例所得缓释材料记为EGCG-MSNs-b。
实施例4
与实施例2不同的是，步骤(1)中氯化铵的加入量为6.0g。本实施例所得缓释材料记为EGCG-MSNs-c。
实施例5
与实施例2不同的是，步骤(1)中CTAB的加入量为6.0g，氯化铵的加入量为6.0g。本实施例所得缓释材料记为EGCG-MSNs-d。
通过制备与人体生理环境相似的人工消化液，模拟缓释材料在胃肠液中的消化，具体如下：
①模拟胃消化
胃消化液配制：在4mL 9mg/mL的NaCl中加入4mL 4mg/mL胃蛋白酶，并用0.1mol/LHCl调节pH至2.0-2.3。4mg/mL胃蛋白酶溶液的配制方法为：称量0.4g胃蛋白酶溶解于0.1mol/L HCl 100mL中。0.1mol/L HCl的配制方法为：向1L蒸馏水中缓慢注入浓度为36-37％的浓盐酸9mL。
向胃消化液中分别加入0.15g各缓释材料，于37℃250r/min震荡2h(用保鲜膜封住)；蒸发至一定体积后冻干，以超纯水复溶至10mL，分析前用0.22μm滤膜过滤。
②模拟肠消化
肠消化液的配制：称量562.5mg的胰蛋白酶、562.5mg的猪胆盐，并加入9mg/mL的氯化钠溶液225mL溶解后，用0.1M NaOH调节pH为7-7.4，并用9mg/mL的氯化钠溶液定容至刻度线。
用1mol/L NaHCO3将胃消化后的样品pH调至7.0-7.2，再加入肠消化液1.8mL，于37℃250r/min震荡2h(同胃消化)；蒸发至一定体积后冻干，以超纯水复溶至10mL，分析前用0.22μm滤膜过滤。
采用N2吸附-脱附分析未经消化样品、经胃消化样品，经胃消化+肠消化样品的吸附特性。依据氮气在材料表面的吸附特性，在一定压力下，材料表面在超低温下对气体分子具有可逆物理吸附作用，通过测量氮气在表面的吸附量和脱附量获得吸附-脱附等温曲线，计算得到材料的比表面积、孔容及孔径等参数。本实验通过Micromeritics ASAP2460型全自动快速比表面与孔隙度分析仪对所制备的介孔二氧化硅进行比表面积、孔径、孔容测定。测量之前先将质量不小于0.1g介孔二氧化硅置于110℃脱气6h。结果如下表所示：
在上表中，每个实施例中的1号样品表示该实施例制备的MSNs，2号样品表示该实施例中制备的MSNs依次经胃消化和肠消化处理后的样品。
3号样品表示该实施例中制备的EGCG-MSNs，4号样品表示该实施例中制备的EGCG-MSNs仅经胃消化处理后的样品，5号样品表示该实施例中制备的EGCG-MSNs依次经胃消化和肠消化处理后的样品。
对比上表中各实施例的1号样品的参数的可知：通过调节CTAB和无机铵的加入量，可以控制二氧化硅载体的孔容和孔径，进而改变负载量。
通过比较上表中每个实施例中3号和4号样品的吸附参数可知，本发明制备的缓释材料在经模拟胃消化处理后，比表面积和孔容均未发生很大变化，说明二氧化硅载体在胃消化液中比较稳定，能够保持完整的球状，说明了载体上负载的多酚物质在胃消化液中通过介孔释放且释放量较少。
通过比较上表中每个实施例中2号、5号样品与其他样品的吸附参数可知，材料的孔容、孔径以及比表面积都发生了显著变化，孔径的增加会导致孔内面积减小，而比表面积包括孔结构的内面积，所以孔径的增加会导致比表面积减小，说明MSNs在肠消化液的弱碱环境中难以维持完整的球状，进而大量释放负载的多酚。
而且从上表可知，通过调整铵盐种类、铵盐添加量、CTAB添加量可以调控多酚的释放规律，具体为：①提高造孔剂氯化铵的加入量，MSNs在胃消化液中的稳定性提高，同时在肠处靶向释放量提高，主要通过载体在消化液中破裂方式而释放EGCG；②提高模板剂CTAB的加入量，MSNs在胃肠消化液中的稳定性略微提高，同时在肠处靶向释放量提高，主要通过介孔进行释放；③使用硫酸铵作为造孔剂，会减少孔容，提高孔径，MSNs在胃肠消化液中的稳定性显著提高。
综上所述，本发明的缓释材料能够有效实现板栗壳多酚在小肠内的靶向释放，避免其在消化过程中因过早释放而降低了小肠吸收效率。
以上仅为本发明的较佳实施例，不用于限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (10)
1.一种小肠靶向释放的板栗壳多酚缓释材料，其特征在于，所述缓释材料包括介孔二氧化硅纳米颗粒以及负载于介孔二氧化硅纳米颗粒内的板栗壳多酚。
2.根据权利要求1所述的板栗壳多酚缓释材料，其特征在于，所述介孔二氧化硅纳米颗粒的粒径为400nm～800nm，且孔径为1.8～6nm。
3.根据权利要求1所述的板栗壳多酚缓释材料，其特征在于，所述板栗壳多酚由乙醇浸提板栗壳所得。
4.根据权利要求1所述的板栗壳多酚缓释材料，其特征在于，所述介孔二氧化硅纳米颗粒的制备包括以下步骤：
S1、在溶剂中加入正硅酸四乙酯、十六烷基三甲基溴化铵和无机铵盐并混合均匀，加入水搅拌得到浑浊溶液，然后加入浓盐酸作为催化剂使溶液澄清；
S2、将澄清溶液雾化成气溶胶液滴，并于氮气环境下干燥液滴得到固体颗粒，煅烧后即得。
5.根据权利要求4所述的板栗壳多酚缓释材料，其特征在于，步骤S1中正硅酸四乙酯、十六烷基三甲基溴化铵和无机铵盐的质量比为5：(2～3)：(2～3)。
6.根据权利要求4所述的板栗壳多酚缓释材料，其特征在于，步骤S2所述干燥的温度为保持350～450℃，所述煅烧的温度为450～550℃。
7.根据权利要求4所述的板栗壳多酚缓释材料，其特征在于，所述无机铵盐为氯化铵或硫酸铵。
8.根据权利要求4所述的板栗壳多酚缓释材料，其特征在于，步骤S1所述溶剂为水或有机溶剂，所述有机溶剂为甲醇、乙醇、丙酮或乙酸乙酯。
9.一种制备权利要求1所述板栗壳多酚缓释材料的方法，其特征在于，将板栗壳多酚溶于无水乙醇，加入介孔二氧化硅纳米颗粒后超声分散，搅拌后降温静置浸渍，离心，洗涤干燥沉淀即得。
10.权利要求1所述板栗壳多酚缓释材料在药物或食品制备中的应用。
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