CN116421715A - 降低血液黏稠,减少血管粥样硬化斑块的益生菌产品 - Google Patents
降低血液黏稠,减少血管粥样硬化斑块的益生菌产品 Download PDFInfo
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- CN116421715A CN116421715A CN202111651961.5A CN202111651961A CN116421715A CN 116421715 A CN116421715 A CN 116421715A CN 202111651961 A CN202111651961 A CN 202111651961A CN 116421715 A CN116421715 A CN 116421715A
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Abstract
本发明公开了一种降低血液黏稠,减少血管粥样硬化斑块的益生菌产品,属于纳豆制品生产工艺技术领域,其原料包括纳豆激酶粉25‑35wt%、空心纳米微球42‑50wt%、益生菌粉15‑25wt%、羧甲基纤维素6‑10wt%、维生素B1 0.5‑1.5wt%。本发明提供了的纳豆激酶和益生菌复合的产品,能相对长时间地黏附在胃肠道壁上,进一步提升了产品在胃肠道部位的停留时间,显著提高了纳豆激酶的吸收效率,避免了功能成分的浪费,具有更好的降低血液黏稠,减少血管粥样硬化斑块,降血栓等效果。
Description
技术领域
本发明属于纳豆制品生产工艺技术领域,特别是降低血液黏稠,减少血管粥样硬化斑块的益生菌产品。
背景技术
随着人们生活水平的提高,饮食结构的改变,因血液黏稠导致的血管粥样硬化、血栓等病患者呈逐渐增多的趋势。现有能软化血管和溶栓的药物中,纳豆激酶因其可直接水解纤维蛋白,半衰期长、特异性强、副作用小,在胃肠道内可保持稳定,可直接口服等优点而引起了广大关注。双歧杆菌、乳杆菌等益生菌对肠道内的胆固醇等脂类物质具有吸附作用,降低肠道对胆固醇的吸收,进而达到降血脂的目的。
现有技术中,中国专利申请CN105747113A提供了一种具有溶栓降血脂功效的纳豆益生菌组合物,该组合物是将双歧杆菌、嗜酸乳杆菌、纳豆粉加入环状糊精、乳糖、海藻糖、谷氨酸钠、维生素E等保护剂中,冷冻干燥后制备成的干粉,起到溶解血栓,降低血脂的功效。又例如CN104366304A提供了一种含有纳豆激酶和益生菌的微胶囊,通过将纳豆均质匀浆后加入益生菌、明胶、环状糊精后,真空冷冻干燥后制成微胶囊制剂。上述这些纳豆和益生菌复合的剂型,虽然能够起到一定的降低血液粘稠度,减少血栓发生,但是这些剂型在胃肠道中停留的时间相对不长,胃肠道对纳豆激酶的吸收有限,纳豆激酶与益生菌发挥的协同效果也有限。
发明内容
针对以上现有技术的不足,本发明提供了能降低血液黏稠,减少血管粥样硬化斑块的益生菌产品,具体通过以下技术实现。
降低血液黏稠,减少血管粥样硬化斑块的益生菌产品,其原料包括纳豆激酶粉25-35wt%、空心纳米微球42-50wt%、益生菌粉15-25wt%、羧甲基纤维素6-10wt%、维生素B10.5-1.5wt%。
本发明提供的益生菌产品,通过利用空心纳米微球负载纳豆激酶和益生菌粉,实现了纳豆激酶和益生菌粉的缓慢释放;同时利用羧甲基纤维素和维生素B1与胃肠道壁的黏附作用,延长了空心纳米微球在胃肠道中停留时间,使得纳豆激酶能够稳定地被胃肠道壁直接吸收而不会被蛋白酶酶解,也更有利于益生菌吸附在胃肠道壁上。
优选地,上述益生菌产品的原料包括纳豆激酶粉28wt%、空心纳米微球46wt%、益生菌粉18wt%、羧甲基纤维素7wt%、维生素B1 1wt%。
优选地,所述空心纳米微球为粒径8-14μm的碳酸钙空心纳米微球、二氧化硅空心纳米微球或壳聚糖空心纳米微球。
更优选地,所述益生菌粉为菌含量为(5-10)×1010cfu/g的青春双歧杆菌菌粉、婴儿双歧杆菌菌粉、两歧双歧杆菌菌粉、长双歧杆菌菌粉、嗜酸乳杆菌菌粉中的至少一种。
进一步优选地,所述益生菌粉为青春双歧杆菌菌粉、长双歧杆菌菌粉和嗜酸乳杆菌的混合,且重量比为1:1:2-4。
一种权利要求1所述的降低血液黏稠,减少血管粥样硬化斑块的益生菌产品的制备方法,包括以下步骤:
S1、取纳豆激酶粉、益生菌粉加入水中混合均匀,加入空心纳米微球,超声搅拌1-1.5h;
S2、在步骤S1的混合液中加入羧甲基纤维素、维生素B1后,继续超声搅拌,冷冻干燥后得到益生菌产品。
优选地,上述益生菌产品制备方法的步骤S1和S2中,超声搅拌的参数为20-30kHz,500W。
与现有技术相比,本发明的有益之处在于:本发明提供了一种能够缓释纳豆激酶和益生菌的复合产品,该产品能相对长时间地黏附在胃肠道壁上,进一步提升了产品在胃肠道部位的停留时间,显著提高了纳豆激酶的吸收效率,避免了功能成分的浪费,具有更好的降低血液黏稠,减少血管粥样硬化斑块,降血栓等效果。
具体实施方式
下面将对本发明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做出创造性劳动条件下所获得的所有其它实施例,都属于本发明保护的范围。
以下实施例和对比例所使用的纳豆激酶粉、益生菌粉(青春双歧杆菌菌粉、婴儿双歧杆菌菌粉、两歧双歧杆菌菌粉、长双歧杆菌菌粉、嗜酸乳杆菌菌粉)、羧甲基纤维素、维生素B1均从市场上常规采购获得,其中,青春双歧杆菌菌粉中的菌含量为(1-10)×1010cfu/g;长双歧杆菌菌粉中的菌含量为(2-5)×1010cfu/g;嗜酸乳杆菌菌粉中的菌含量为(5-10)×109cfu/g。空心纳米微球采购的是碳酸钙空心纳米微球,粒径10μm左右。
实施例1
本实施例提供的益生菌产品,其原料包括纳豆激酶粉28wt%、空心纳米微球46wt%、益生菌粉18wt%、羧甲基纤维素7wt%、维生素B1 1wt%。
本实施例提供的益生菌产品的制备方法是:取纳豆激酶粉、益生菌粉加入水中混合均匀,加入空心纳米微球,超声搅拌(20-30kHz,500W)1.5h;然后在混合液中加入羧甲基纤维素、维生素B1后,继续超声搅拌(20-30kHz,500W),冷冻干燥后得到益生菌产品。制备得到的益生菌产品为干粉状,粒径约为80-115μm。
实施例2
本实施例提供的益生菌产品,其原料包括纳豆激酶粉25wt%、空心纳米微球50wt%、益生菌粉15wt%、羧甲基纤维素9.5wt%、维生素B1 0.5wt%。益生菌产品的制备方法与实施例1相同。制备得到的益生菌产品为干粉状,粒径约为95-110μm。
实施例3
本实施例提供的益生菌产品,其原料包括纳豆激酶粉35wt%、空心纳米微球42wt%、益生菌粉15.5wt%、羧甲基纤维素6wt%、维生素B1 1.5wt%。益生菌产品的制备方法与实施例1相同。制备得到的益生菌产品为干粉状,粒径约为80-125μm。
对比例1
本对比例提供的益生菌产品,其原料包括纳纳豆激酶粉46wt%、空心纳米微球46wt%、羧甲基纤维素7wt%、维生素B1 1wt%。益生菌产品的制备方法为:取纳豆激酶粉加入水中混合均匀,加入空心纳米微球,超声搅拌(20-30kHz,500W)1.5h;然后在混合液中加入羧甲基纤维素、维生素B1后,继续超声搅拌(20-30kHz,500W),冷冻干燥后得到益生菌产品。制备得到的益生菌产品为干粉状,粒径约为78-100μm。
对比例2
本对比例提供的益生菌产品,其原料包括纳豆激酶粉28wt%、空心纳米微球46wt%、益生菌粉18wt%、羧甲基纤维素8wt%。益生菌产品的制备方法为:取纳豆激酶粉加入水中混合均匀,加入空心纳米微球,超声搅拌(20-30kHz,500W)1.5h;然后在混合液中加入羧甲基纤维素后,继续超声搅拌(20-30kHz,500W),冷冻干燥后得到益生菌产品。制备得到的益生菌产品为干粉状,粒径约为110-125μm。
对比例3
本对比例提供的益生菌产品,其原料包括纳豆激酶粉28wt%、空心纳米微球46wt%、益生菌粉18wt%、维生素B1 8wt%。益生菌产品的制备方法为:取纳豆激酶粉加入水中混合均匀,加入空心纳米微球,超声搅拌(20-30kHz,500W)1.5h;然后在混合液中加入维生素B1后,继续超声搅拌(20-30kHz,500W),冷冻干燥后得到益生菌产品。制备得到的益生菌产品为干粉状,粒径约为75-1-100μm。
试验例1:益生菌产品的体外粘附性试验
参考中国专利申请CN1528271A的方法,对实施例1-3和对比例1-3制备的益生菌产品进行在小鼠/大鼠体内和体外的粘附性考察。
1、益生菌产品的体外粘附性考察
采用胃粘膜冲洗法:取禁食、给水24h的小鼠,断颈处死后取胃组织,自贲门口处剪开,用生理盐水冲洗干净后剪成1cm×1cm块状后平铺于载玻片上;在胃粘膜表面上撒上80粒益生菌产品微球,用生理盐水润湿后,置于相对湿度为90%的密闭容器内,保湿20min;取出固定在45°斜面上,以pH值=1.3的稀盐酸-氯化钠溶液冲洗(20mL/min)胃组织的黏膜5min;计数胃黏膜表面滞留的微球个数,即计算出滞留百分率,如下表1所示。
表1益生菌产品的体外粘附性试验结果
组名 | 实施例1 | 实施例2 | 实施例3 | 对比例1 | 对比例2 | 对比例3 |
滞留百分率 | 93.75% | 95% | 86.25% | 91.25% | 72.5% | 77.5% |
2、益生菌产品的体内粘附性考察
取体重为230±10g的SD大鼠36只,禁食、给水24小时后,随机分成6组;取内径约2.5mm的塑料管,一端封口后,装入80粒微球,另一端接5ml注射器;当塑料管插入大鼠胃内后,以2ml生理盐水将微球注入大鼠胃内。记录每只大鼠灌胃时间。给药后大鼠禁食禁水,每组于2、4、8h断颈分别处死2只大鼠。解剖大鼠,取出小肠,剪开,分别计数大鼠小肠中的微球个数,计算滞留百分率,如下表2所示。
表2益生菌产品的体内粘附性试验结果
由上表1、2可以看到,采用实施例1-3的方法制备成的益生菌产品,在小鼠/大鼠的胃/肠道上粘附的效果更好。而缺少羧甲基纤维素、维生素B1中任意一个,都会对空心纳米微球在胃肠道的粘附效果产生影响。
试验例2:益生菌产品降血脂效果验证
参考申请人于2020年08月18日获得授权的中国专利CN106798252B中公开的验证方法,选取实施例1-3和对比例1-3制备的益生菌产品,随机选取6周龄左右的雄性Waster大鼠,以基础饲料正常饲养7天后,取鼠尾血,检测大鼠的血脂,按TC水平,将动物随机分为数量相同的空白对照组、高脂模型组、实施例1-3组和对比例1-3组,除对照组饲喂基础饲料外,其余大鼠饲喂高脂饲料(高脂饲料:基础饲料78.8%,猪油10%,胆固醇1%,蛋黄粉10%,胆盐0.2%);
各组药量为:空白对照组灌胃等体积的生理盐水;高脂模型组灌胃等体积的生理盐水;实施例1-3组和对比例1-3组,分别灌胃2.5g/kg的实施例1-3和对比例1-3制备的益生菌产品;
连续给药30天,30天后禁止大鼠进食并称重,禁食第二日,取鼠尾抽血,分别检测大鼠血清的TC(总胆固醇)、TG(甘油三酯)。运用SPSS软件对实验数据进行方差分析统计,在上述三个指标中,如果血清的TC(总胆固醇)、TG(甘油三酯)这两个指标为阳性,即可判断受试样品的降血脂功能动物实验为阳性。
试验结果如表3-表5所示。
表3各组大鼠试验前后体重变化情况(X±S)
由表3可以看到,随着喂食时间增加,所有试验动物体重皆上升,其中,实施例1-3组的大鼠增重相对较少。各组动物生长、活动正常,高脂模型组的动物体重增长程度明显大于空白对照组,实施例1-3组、对比例1-3组与空白对照组相比,体重增长程度有所增加。
表4各组大鼠试验前后TG变化情况
由表4可以看到,给予高脂饲料前,各组大鼠血清甘油三酯TG含量较均衡,各组间差异不显著(P>0.05)。到第30天,高脂模型组的大鼠TG含量明显高于空白对照组,这说明高脂动物模型成功建立。试验到第30天,实施例1-3组、对比例1-3组的大鼠TG含量均低于高脂模型组,且实施例1-3组与高脂模型组的差异相对更明显,这说明采用实施例1-3制备的益生菌产品能够有效降低高脂动物模型中的血清甘油三酯TG含量。对比例1未使用益生菌粉,对比例2未使用维生素B1,对比例3未使用羧甲基纤维素,其对降低TG含量的效果相对较差,这说明只有同时使用益生菌粉和纳豆激酶,或者同时使用维生素B1和羧甲基纤维素,才能够达到本发明提到的显著降血脂的作用。
表5各组大鼠试验前后TC情况
由表5可以看到,各组大鼠的血清总胆固醇TC含量在实验前各组间的差异不大。到第30天,高脂模型组的TC含量明显高于空白对照组,说明高脂动物模型成功建立。试验到第30天,实施例1-3组、对比例1-3组大鼠的TC含量均低于高脂模型组,且实施例1-3组与高脂模型组的差异明显,这说明实施例1-3制备的益生菌产品具有降低饲喂高脂饲料大鼠的血清总胆固醇TC含量的作用。对比例1未使用益生菌粉,对比例2未使用维生素B1,对比例3未使用羧甲基纤维素,其对降低TC含量的效果相对较差,这说明只有同时使用益生菌粉和纳豆激酶,或者同时使用维生素B1和羧甲基纤维素,才能够达到本发明提到的显著降血脂的作用。
试验例3:益生菌产品溶血栓效果验证
参考申请人于2020年08月18日获得授权的中国专利CN106798252B中公开的验证方法,选取实施例1-3和对比例1-3制备的益生菌产品,随机选取大耳白兔,雌雄各半,体重2.0±0.2kg。将选取的大耳白兔在给药前逐只进行颈总动脉分离,游离出约2cm长近心端和远心端,用小动脉夹夹住,让血液在血管内通过,1.5h后,颈动脉内血栓形成,分别给大耳白兔灌胃2g/kg实施例1-3和对比例1-3的益生菌产品,另外设空白对照组灌胃等体积生理盐水,5小时后处死大耳白兔,剪下颈动脉血管,剖开血管取出丝线和血栓,量取1cm长,称其重量,然后将血栓放于烘箱中60℃烘干,计算颈动脉血栓的湿重与干重,并与生理盐水比较,检查有无显著性差异,结果如表6所示。
表6各组大耳白兔血栓溶解情况
由表6可以看到,给形成颈总动脉血栓的大耳白兔灌胃本发明实施例1-3制备的益生菌产品后,无论是血栓的湿重或干重,结果均显示出明显的溶栓作用。对比例1未使用益生菌粉,对比例2未使用维生素B1,对比例3未使用羧甲基纤维素,其益生菌产品虽也有一定的溶血栓效果,但明显不如实施例1-3,说明只有同时使用益生菌粉和纳豆激酶,或者同时使用维生素B1和羧甲基纤维素,才能够达到本发明提到的显著的溶血栓的作用。
Claims (7)
1.降低血液黏稠,减少血管粥样硬化斑块的益生菌产品,其特征在于,其原料包括纳豆激酶粉25-35wt%、空心纳米微球42-50wt%、益生菌粉15-25wt%、羧甲基纤维素6-10wt%、维生素B1 0.5-1.5wt%。
2.根据权利要求1所述的降低血液黏稠,减少血管粥样硬化斑块的益生菌产品,其特征在于,其原料包括纳豆激酶粉28wt%、空心纳米微球46wt%、益生菌粉18wt%、羧甲基纤维素7wt%、维生素B1 1wt%。
3.根据权利要求1所述的降低血液黏稠,减少血管粥样硬化斑块的益生菌产品,其特征在于,所述空心纳米微球为粒径8-14μm的碳酸钙空心纳米微球、二氧化硅空心纳米微球或壳聚糖空心纳米微球。
4.根据权利要求1-3任一项所述的降低血液黏稠,减少血管粥样硬化斑块的益生菌产品,其特征在于,所述益生菌粉为菌含量为(5-10)×1010cfu/g的青春双歧杆菌菌粉、婴儿双歧杆菌菌粉、两歧双歧杆菌菌粉、长双歧杆菌菌粉、嗜酸乳杆菌菌粉中的至少一种。
5.根据权利要求4所述的降低血液黏稠,减少血管粥样硬化斑块的益生菌产品,其特征在于,所述益生菌粉为青春双歧杆菌菌粉、长双歧杆菌菌粉和嗜酸乳杆菌的混合,且重量比为1:1:2-4。
6.一种权利要求1所述的降低血液黏稠,减少血管粥样硬化斑块的益生菌产品的制备方法,其特征在于,包括以下步骤:
S1、取纳豆激酶粉、益生菌粉加入水中混合均匀,加入空心纳米微球,超声搅拌1-1.5h;
S2、在步骤S1的混合液中加入羧甲基纤维素、维生素B1后,继续超声搅拌,冷冻干燥后得到益生菌产品。
7.根据权利要求6所述的降低血液黏稠,减少血管粥样硬化斑块的益生菌产品的制备方法,其特征在于,步骤S1和S2中,超声搅拌的参数为20-30kHz,500W。
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