CN114009783A - 一种肠溶益生菌和益生元复合制剂的制备方法 - Google Patents
一种肠溶益生菌和益生元复合制剂的制备方法 Download PDFInfo
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- CN114009783A CN114009783A CN202111152062.0A CN202111152062A CN114009783A CN 114009783 A CN114009783 A CN 114009783A CN 202111152062 A CN202111152062 A CN 202111152062A CN 114009783 A CN114009783 A CN 114009783A
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Abstract
本发明涉及益生菌和益生元制剂领域，特别公开了一种肠溶益生菌和益生元复合制剂的制备方法。本发明通过可食用材料进行包埋益生菌，使最终制剂耐酸、耐高温，同时贮存和使用过程方便，不用担心高温益生菌失活的情况出现；益生菌通过真空冷冻干燥工艺，水分含量极低，将其与食用油混悬，大大延长了产品的保质期，产品的销售运输过程中，不用使用特殊运输装置，减少运输成本，使产品价格更加亲民，销售空间增大。本发明肠溶益生菌和益生元的制备工艺相对简单，包埋率高，加工成本低，适用于工业化生产。
Description
技术领域
本发明涉及益生菌和益生元制剂领域，特别涉及一种肠溶益生菌和益生元复合制剂的制备方法。
背景技术
进入21世纪，随着生物技术的进步与发展，各种生物活性功能性成分在体内的代谢和作用被进一步揭示，消费者出于健康意识的不断提升，对食品中的特定功能性追求越来越强烈。截止2019年，全球益生菌补充剂行业规模达61亿美元，而中国的行业规模达42.4亿元人民币，同比增长18%。益生菌市场近年来一直维持在15%~18%的增速，远高于全球5%的平均增速，在消费升级趋势下，国内益生菌产品市场逐渐进入“档次高、品种多”的成熟期，品种差异化的益生菌产品今后将得到市场更多青睐。
益生菌在人体内发挥生物屏障功能，参与免疫系统成熟和免疫应答的调节、并对机体内多种生理代谢起着重要作用，其作用机制有以下几方面：补充肠道有益菌，在肠黏膜上形成一层“膜菌群”增强体内屏障功能，抑制肠道有害菌的生长，阻止致病菌的侵入及繁殖，调整肠道菌群；发酵糖类，产生醋酸及乳酸，促进肠蠕动，合成多种维生素和生物酶激活机体吞噬细胞的吞噬活性，提高免疫能力，减少内毒素的来源等。
维持益生菌的活力是非常困难的，大多数益生菌的抗性较差，在加工、运输和储存过程中极易受外界光、温度、氧气等环境条件的影响而失活。在摄食后，益生菌还面临复杂的胃肠道环境的考验，低pH值、胆汁、胰液和高浓度的消化酶都是典型应激因素，处于极端的生化环境压力下，益生菌的肠道输送面临着诸多挑战。
益生菌常以胶囊、粉剂、颗粒剂、片剂等形式存在于营养保健品市场中。但是普通的益生菌制剂在口服过程中受到高温和胃液的影响，真正达到肠道起作用的活菌数很少。所以需要将益生菌制剂制备成肠溶制剂，在室温条件下可以长期贮存，且能抵御胃液、胆酸盐的破坏，到达肠道发挥作用。
发明内容
本发明为了弥补现有技术的不足，提供了一种工艺相对简单、加工成本低、适于工业化生产的肠溶益生菌和益生元复合制剂的制备方法。
本发明是通过如下技术方案实现的：
一种肠溶益生菌和益生元复合制剂的制备方法，包括如下步骤：
（1）将益生菌在培养基中活化，之后接种到培养液中发酵，发酵后对培养液进行低温高速离心处理，得到菌体；
（2）将菌体用缓冲液清洗后用两倍重量的冻干保护剂重悬，将重悬液真空冷冻干燥、研磨、过筛，得到益生菌复合粉；
（3）将益生菌复合粉混悬于植物油中，并经均质得到益生菌菌悬液；
（4）将基质材料溶于水中，搅拌溶解得到质量浓度为1.5-8%的肠溶基质；
（5）将肠溶基质置于加热物料罐中，将益生菌菌悬液置于常温芯料罐中，启动机器冷凝装置，将物料和芯料同时输出进行包埋球粒的制备，将制备的球粒钙化、风干，得到肠溶益生菌球粒；
（6）将天然植物通过清洗、粉碎、匀浆、提取、干燥得到益生元粉，向益生元粉中添加糖醇类添加剂，置于湿法制粒机中预混，然后加入羧甲基纤维素钠搅拌、切碎，之后制粒、干燥，得到益生元颗粒；
（7）分别将益生菌球粒和益生元颗粒置于左右料斗中，按1:2-1:15的比例分装，即得到产品。
本申请为了改善现有益生菌的冲服效果，利用可食用肠溶材料和先进的生产工艺保护益生菌不受胃液和胆酸盐破坏，并添加益生元颗粒，增殖益生菌，达到改善肠道菌群的目的。
本发明的更优技术方案为：
步骤（1）中，益生菌为长双歧杆菌、鼠李糖乳杆菌、罗伊氏乳杆菌、嗜酸乳杆菌、副干酪乳杆菌、植物乳杆菌、拉曼乳杆菌、嗜热双歧杆菌中的一种或多种。
进一步优选的，益生菌的菌体活性总数≥50亿cfu/ml，其分别按照0.2%-0.8%的接种量接种到培养液中，发酵温度控制在37℃，pH控制在5.0-6.8，发酵时长10-18h；颜色棕褐色，有发酵特有气味，菌体形态正常，无其他杂菌形态，10000rpm条件下将培养液离心处理，弃去上清液，得到菌体。
更进一步优选的，发酵时培养液pH控制在5.5-6.5，发酵时长12-15h。
步骤（2）中，将菌体用缓冲液清洗2-3次后重悬，冻干保护剂为糊精、脱脂奶粉、甘露醇和海藻糖中的一种或多种，将重悬液真空冷冻干燥12h，得到的冻干品研磨后过200目筛。
步骤（3）中，益生菌复合粉与植物油的质量百分比为10-25%：75-90%，于800rpm条件下混悬2h，并将其通过高压均质机进行均质。
步骤（4）中，基质材料为琼脂、明胶、海藻酸钠、羟丙甲纤维素、聚乙二醇和甘油中的三种及以上，基质材料于70-80℃下在磁力搅拌器上搅拌溶解60min。
步骤（5）中，将物料以100-150r/min、芯料以20-40r/min的速度进行包埋球粒的制备，将制备的球粒置于氯化钙中钙化1-2min，并用酒精消除表面的油迹，用冷风吹干，得到肠溶益生菌球粒。
步骤（6）中，天然植物为菊苣、葛根、茯苓、枸杞、甜叶菊中的一种或多种，糖醇类添加剂为赤藓糖醇、低聚果糖、低聚半乳糖、低聚棉籽糖、抗性糊精中的一种或多种；糖醇类添加剂、羧甲基纤维素钠与益生元粉的质量比为0.3-0.7:0.005-0.03：1。
进一步优选的，益生菌粉和糖醇类添加剂置于湿法制粒机中，50Hz预混3-5min，然后加入羧甲基纤维素钠，50Hz搅拌1min，切碎1min，继续再搅拌1min，切碎1min，收料；用摇摆制粒机制粒，后用沸腾干燥机进行干燥，待水分≤3.0后，停止，得到益生元颗粒。
本发明通过可食用材料进行包埋益生菌，使最终制剂耐酸、耐高温，同时贮存和使用过程方便，不用担心高温益生菌失活的情况出现；益生菌通过真空冷冻干燥工艺，水分含量极低，将其与食用油混悬，大大延长了产品的保质期，产品的销售运输过程中，不用使用特殊运输装置，减少运输成本，使产品价格更加亲民，销售空间增大。
本发明的益生菌是肠溶益生菌，可避免胃酸及胆酸盐的侵蚀，为益生菌在肠道存活和定殖提供了稳定的生态环境，肠溶益生菌和益生元的制备工艺相对简单，包埋率高，加工成本低，适用于工业化生产。
具体实施方式
下面结合具体实施例对本发明的技术方案进行详细说明，以便于对本发明的理解，但并不是对本发明的限制。
实施例1：一种肠溶益生菌和益生元复合制剂的制备方法
具体包括如下步骤：
（1）益生菌菌种的活化和发酵培养：
将长双歧杆菌、鼠李糖乳杆菌、罗伊氏乳杆菌在培养基中活化，之后分别按照0.8%接种量接种到培养液中，37℃发酵14h，pH控制在5.5-6.0；之后于4℃、10000rpm条件下低温高速离心处理，弃去上清液，得到菌体；
（2）益生菌冻干粉的制备方法：
菌体用缓冲液清洗2-3次后用两倍重量的糊精、脱脂乳粉混合制剂重悬，将重悬液进行冷冻干燥12h，得到冻干品，将冻干品进行研磨，过200目筛，即得益生菌复合粉；
（3）益生菌菌悬液的制备：
将益生菌复合粉250g混悬于750g植物油中，800rpm条件下混悬2h，高压均质机进行均质，得到益生菌菌悬液；
（4）肠溶基质的制备：
将海藻酸钠6g、明胶5g、羟丙甲纤维素10g和甘油5g溶于1L水中，70-80℃搅拌溶解60min，得到肠溶基质；
（5）包埋球粒的制备：
将肠溶基质置于加热物料灌中，益生菌菌悬液置于常温芯料罐中，启动机器冷凝装置，物料以100r/min，芯料以40r/min的速度进行包埋球粒的制备，将制备的球粒置于氯化钙中钙化1-2min，并用酒精清除表面的油迹，用冷风吹干，得到肠溶益生菌球粒；
（6）益生元颗粒的制备：
选取菊苣、葛根、茯苓通过清洗、粉碎、匀浆、提取、干燥得到益生元粉；将益生元粉3kg与赤藓糖醇1kg、低聚棉子糖0.5kg、抗性糊精0.5kg置于湿法制粒机中，50Hz预混3min，然后加入1%羧甲基纤维素钠50g，搅拌制粒；沸腾干燥机进行干燥，待水分≤3.0后，停止，得到益生元颗粒；
（7）复合制剂的粉状
分别将益生菌球粒和益生元颗粒分别置于左右料斗内，按1:5的比例分装，即得肠溶益生菌和益生元复合制剂。
采用食品安全国家标准GB 4789.35-2016规定的检测方法，对本实施例制备的复合制剂进行活菌检测，该复合制剂中活菌数量为338亿CFU/4.5g复合制剂。
实施例2：一种肠溶益生菌和益生元复合制剂的制备方法
具体包括如下步骤：
（1）将干酪乳杆菌、鼠李糖乳杆菌、植物乳杆菌在培养基中活化，之后分别按照0.4%接种量接种到培养液中，37℃发酵16h，pH控制在5.5-6.4；之后于4℃，10000rpm条件下低温高速离心处理，弃去上清液，得到菌体；
（2）菌体用缓冲液清洗2-3次后用两倍重量的糊精、脱脂乳粉的混合剂重悬，将重悬液进行冷冻干燥12h，得到冻干品，将冻干品进行研磨，过200目筛，即得益生菌复合粉；
（3）将益生菌复合粉100g混悬于900g植物油中，800rpm条件下混悬2h，高压均质机进行均质，得到益生菌菌悬液；
（4）将海藻酸钠10g、羟丙甲纤维素5g和甘油5g溶于1L水中，70-80℃搅拌溶解60min，得到质量浓度为7%的肠溶基质；
（5）将肠溶基质置于加热物料灌中，益生菌菌悬液置于常温芯料罐中，启动机器冷凝装置，物料以150r/min，芯料以30r/min的速度进行包埋球粒的制备，将制备的球粒置于氯化钙中钙化1-2min，并用酒精清除表面的油迹，用冷风吹干，得到肠溶益生菌球粒；
（6）选取菊苣、枸杞、茯苓通过清洗、粉碎、匀浆、提取、干燥得到益生元粉；将益生元粉5kg与赤藓糖醇1kg、低聚棉子糖1kg、低聚果糖1.5kg置于湿法制粒机中，50Hz预混4min，然后加入1.5%羧甲基纤维素钠50g，搅拌制粒；沸腾干燥机进行干燥，待水分≤3.0后，停止，得到益生元颗粒；
（7）分别将益生菌球粒和益生元颗粒分别置于左右料斗内，按1:8的比例分装，即得肠溶益生菌和益生元的复合制剂。
采用食品安全国家标准GB 4789.35-2016规定的检测方法，对本实施例制备的复合制剂进行活菌检测，该复合制剂中活菌数量为132亿CFU/4.5g复合制剂。
本发明涉及益生菌和益生元制剂生产领域，特别公开了一种肠溶益生菌和益生元复合制剂及其制备方法。本发明通过可食用材料进行包埋益生菌，使最终制剂耐酸、耐高温，同时贮存、使用和运输方便，节约成本，可广泛应用于食品、保健品和药品领域。
在上述实施例中，对本发明的最佳实施方式做了描述，很显然，在本发明的发明构思下，仍可做出很多变化。在此，应该说明，在本发明的发明构思下所做出的任何改变都将落入本发明的保护范围内。
Claims (10)
1.一种肠溶益生菌和益生元复合制剂的制备方法，其特征为，包括如下步骤：（1）将益生菌在培养基中活化，之后接种到培养液中发酵，发酵后对培养液进行低温高速离心处理，得到菌体；（2）将菌体用缓冲液清洗后用两倍重量的冻干保护剂重悬，将重悬液真空冷冻干燥、研磨、过筛，得到益生菌复合粉；（3）将益生菌复合粉混悬于植物油中，并经均质得到益生菌菌悬液；（4）将基质材料溶于水中，搅拌溶解得到质量浓度为1.5-8%的肠溶基质；（5）将肠溶基质置于加热物料罐中，将益生菌菌悬液置于常温芯料罐中，启动机器冷凝装置，将物料和芯料同时输出进行包埋球粒的制备，将制备的球粒钙化、风干，得到肠溶益生菌球粒；（6）将天然植物通过清洗、粉碎、匀浆、提取、干燥得到益生元粉，向益生元粉中添加糖醇类添加剂，置于湿法制粒机中预混，然后加入羧甲基纤维素钠搅拌、切碎，之后制粒、干燥，得到益生元颗粒；（7）分别将益生菌球粒和益生元颗粒置于左右料斗中，按1:2-1:15的比例分装，即得到产品。
2.如权利要求1所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：步骤（1）中，益生菌为长双歧杆菌、鼠李糖乳杆菌、罗伊氏乳杆菌、嗜酸乳杆菌、副干酪乳杆菌、植物乳杆菌、拉曼乳杆菌、嗜热双歧杆菌中的一种或多种。
3.如权利要求1所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：步骤（1）中，益生菌的菌体活性总数≥50亿cfu/ml，其分别按照0.2%-0.8%的接种量接种到培养液中，发酵温度控制在37℃，pH控制在5.0-6.8，发酵时长10-18h；颜色棕褐色，有发酵特有气味，菌体形态正常，无其他杂菌形态，10000rpm条件下将培养液离心处理，弃去上清液，得到菌体。
4.如权利要求3所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：发酵时培养液pH控制在5.5-6.5，发酵时长12-15h。
5.如权利要求1所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：步骤（2）中，将菌体用缓冲液清洗2-3次后重悬，冻干保护剂为糊精、脱脂奶粉、甘露醇、海藻糖中的一种或多种，将重悬液真空冷冻干燥12h，得到的冻干品研磨后过200目筛。
6.如权利要求1所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：步骤（3）中，益生菌复合粉与植物油的质量百分比为10-25%：75-90%，于800rpm条件下混悬2h，并将其通过高压均质机进行均质。
7.如权利要求1所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：步骤（4）中，基质材料为琼脂、明胶、海藻酸钠、羟丙甲纤维素、聚乙二醇和甘油中的三种及以上，基质材料于70-80℃下在磁力搅拌器上搅拌溶解60min。
8.如权利要求1所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：步骤（5）中，将物料以100-150r/min、芯料以20-40r/min的速度进行包埋球粒的制备，将制备的球粒置于氯化钙中钙化1-2min，并用酒精消除表面的油迹，用冷风吹干，得到肠溶益生菌球粒。
9.如权利要求1所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：步骤（6）中，天然植物为菊苣、葛根、茯苓、枸杞、甜叶菊中的一种或多种，糖醇类添加剂为赤藓糖醇、低聚果糖、低聚半乳糖、低聚棉籽糖、抗性糊精中的一种或多种；糖醇类添加剂、羧甲基纤维素钠与益生元粉的质量比为0.3-0.7:0.005-0.03：1。
10.如权利要求1所述的肠溶益生菌和益生元复合制剂的制备方法，其特征在于：步骤（6）中，益生菌粉和糖醇类添加剂置于湿法制粒机中，50Hz预混3-5min，然后加入羧甲基纤维素钠，50Hz搅拌1min，切碎1min，继续再搅拌1min，切碎1min，收料；用摇摆制粒机制粒，后用沸腾干燥机进行干燥，待水分≤3.0后，停止，得到益生元颗粒。
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