CN112194595A - 一种化合物、中药益生菌发酵产物及其在制备具有降胆固醇作用的药物或保健品中的应用 - Google Patents
一种化合物、中药益生菌发酵产物及其在制备具有降胆固醇作用的药物或保健品中的应用 Download PDFInfo
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Abstract
本发明涉及生物医学技术领域,具体公开了一种化合物、中药益生菌发酵产物及其在制备具有降胆固醇作用的药物或保健品中的应用。所述的化合物具有式(Ⅰ)所示的结构。所述的中药益生菌发酵产物,包含式(Ⅰ)化合物;其制备方法包含如下步骤:(1)取中药原料用益生菌进行发酵,得发酵液;(2)将发酵液进行干燥后即得所述的中药益生菌发酵产物;步骤(1)中所述的中药原料为包含山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的中药原料。本发明所述的式(Ⅰ)化合物以及中药益生菌发酵产物具有优异的降胆固醇和抗炎作用,可以用于制备药物和保健品。
Description
技术领域
本发明涉及生物医学技术领域,具体涉及一种化合物、中药益生菌发酵产物及其在制备具有降胆固醇作用的药物或保健品中的应用。
背景技术
心血管疾病是导致世界范围内死亡和残疾的主要原因。动脉粥样硬化是心血管疾病发生和进一步急性并发症的罪魁祸首,高胆固醇水平可导致严重的动脉粥样硬化,高胆固醇血症患者的心脏病发作的风险是正常患者的三倍。胆固醇对于细胞功能和完整性有重要作用,低密度脂蛋白胆固醇在血管中聚集可改变细胞的渗透性影响血管,导致血管中形成动脉粥样硬化病变,引发高血压和高血脂症。治疗心血管疾病的主要药物是他汀类药物,但他汀类药物会引发肝酶和肌痛等不良反应,因此,了解其他有助于降低高胆固醇水平的因素以开发新的预防和治疗策略十分重要。
益生菌是一种大量口服时对人体健康有益的活细菌。有研究表明,营养摄入益生菌可以通过调节血清胆固醇水平降低高胆固醇血症和冠状动脉疾病等心血管疾病的威胁。在2016年,Kullisaar等人报告所有申请人在食用含食品补充剂RAC的发酵乳杆菌4周后,其总胆固醇、低密度脂蛋白胆固醇和氧化低密度脂蛋白水平都有显著的降低;Ngongang等人也表明大鼠动物模型在连续摄入含有益生菌菌株的酸奶后,其LDL/HDL胆固醇比显著降低,降低了心血管疾病的风险。中草药中含有许多增强免疫的营养成分和生物活性物质,能够预防疾病、调节肠道菌群的平衡,已成为治疗各种生理疾病的替代方法。
但目前尚无以中药为原料用益生菌发酵制备降胆固醇药物的研究报道。
发明内容
鉴于此,本发明首先提供一种新化合物,经进一步研究表明,该新化合物具有降胆固醇作用和抗炎作用。
此外,本发明还提供一种中药益生菌发酵产物,该中药益生菌发酵产物同样具有降胆固醇作用和抗炎作用。
另外,本发明还提供了一种上述新化合物和中药益生菌发酵产物的制备方法以及应用。
本发明的详细技术方案如下:
一种式(Ⅰ)化合物或其可药用盐;
式(Ⅰ)化合物命名为:
methyl O-benzyl-N-((2,4-dimethoxybenzoyl)glycyl)serinate。
优选地,所述可药用盐为可药用酸加成盐,其中所述酸选自:柠檬酸、酒石酸、乳酸、乙酸、琥珀酸、甲磺酸、乙磺酸、苯磺酸、对甲苯磺酸、丙酮酸、富马酸、马来酸、盐酸、氢溴酸、硝酸、磷酸和硫酸。
本发明还提供一种式(Ⅰ)化合物的制备方法,其包含如下步骤:
(1)取中药原料用益生菌进行发酵,得发酵液;
(2)将发酵液进行干燥后得粗产物;
(3)将粗产物用色谱技术进行分离,即得式(Ⅰ)化合物;
步骤(1)中所述的中药原料为包含山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的中药原料;或为包含山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物的中药原料;
步骤(1)中所述的益生菌选自嗜酸乳杆菌、婴儿双歧杆菌、短双歧杆菌中的一种或二种以上的混合。
本发明中涉及的提取物均是常规的医药原料,可以通过购买得到。也可以采用乙醇或水等常规的溶剂通过常规的方法(如加热回流提取、超声提取或浸提等方法)提取得到。
优选地,步骤(1)的具体方法为:取中药原料、益生菌干粉以及水混合后,在温度为20~30℃、pH为5~6的条件下发酵16~30h,得发酵液;
所述中药原料、益生菌干粉以及水的重量用量比为:20~40:8~15:40~60。
优选地,步骤(1)中所述的中药原料中山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的重量用量比为1~5:1~5:1~5:1~5:1~5:1~5:1~5。
最优选地,步骤(1)中所述的山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的重量用量比为1:1:1:1:1:1:1。即各中药原料用量相等。
优选地,步骤(1)中所述的中药原料中山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物的重量用量比为1~5:1~5:1~5:1~5:1~5:1~5:1~5。
最优选地,步骤(1)中所述的中药原料中山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物的重量用量比为1:1:1:1:1:1:1。即各中药提取物用量相等。
优选地,步骤(1)中所述的益生菌干粉由嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉组成;其中嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉的重量用量比为1~5:1~5:1~5。
最优选地,嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉的重量用量比为1:1:1。
优选地,步骤(3)中所述的色谱技术为制备型HPLC技术;所述的制备型HPLC技术的具体条件为:采用反相色谱柱;选用紫外检测器,检测波长为220~230nm;以0.05~0.2体积%的三氟乙酸水溶液为流动相A,以0.05~0.2体积%的三氟乙酸乙腈溶液为流动相B,流动相A:流动相B=88:12;收集13.6~14.1min色谱峰对应的部位,浓缩干燥后即得式(Ⅰ)化合物。
本发明还提供一种中药益生菌发酵产物,其包含式(Ⅰ)化合物。
本发明还提供一种中药益生菌发酵产物的制备方法,其包含如下步骤:
(1)取中药原料用益生菌进行发酵,得发酵液;
(2)将发酵液进行干燥后即得所述的中药益生菌发酵产物;
步骤(1)中所述的中药原料为包含山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的中药原料;或为包含山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物的中药原料;
步骤(1)中所述的益生菌选自嗜酸乳杆菌、婴儿双歧杆菌、短双歧杆菌中的一种或二种以上的混合。
本发明中涉及的提取物均是常规的医药原料,可以通过购买得到。也可以采用乙醇通过常规的方法(如加热回流提取、超声提取或浸提等方法)提取得到。
优选地,步骤(1)的具体方法为:取中药原料、益生菌干粉以及水混合后,在温度为20~30℃、pH为5~6的条件下发酵16~30h,得发酵液;
所述中药原料、益生菌干粉以及水的重量用量比为:20~40:8~15:40~60。
优选地,步骤(1)中所述的中药原料中山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的重量用量比为1~5:1~5:1~5:1~5:1~5:1~5:1~5。
最优选地,步骤(1)中所述的山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的重量用量比为1:1:1:1:1:1:1。即各中药原料用量相等。
优选地,步骤(1)中所述的中药原料中山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物的重量用量比为1~5:1~5:1~5:1~5:1~5:1~5:1~5。
最优选地,步骤(1)中所述的中药原料中山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物的重量用量比为1:1:1:1:1:1:1。即各中药提取物用量相等。
优选地,步骤(1)中所述的益生菌干粉由嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉组成;其中嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉的重量用量比为1~5:1~5:1~5。
最优选地,嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉的重量用量比为1:1:1。
本发明还提供一种式(Ⅰ)化合物或其可药用盐或中药益生菌发酵产物在制备药物或保健品中的应用。
优选地,所述的药物为具有降胆固醇作用的药物,或具有抗炎作用的药物;
所述的保健品为具有降胆固醇作用的保健品。
优选地,所述的药物或保健品含有式(Ⅰ)化合物或其可药用盐或中药益生菌发酵产物和载体;所述式(Ⅰ)化合物或其可药用盐或中药益生菌发酵产物的质量分数为5%~95%。
进一步优选地,所述载体包括溶剂、聚合物和脂质体中的至少一种。更进一步优选地,所述溶剂包括但不限于水、生理盐水,以及其他非水性溶剂。更进一步优选地,所述聚合物包括但不限于为聚赖氨酸、聚乙烯亚胺及其改性物、壳聚糖、聚乳酸、明胶。更进一步优选地,所述脂质体可以但不限于为胆固醇、豆卵磷脂、蛋黄卵磷脂。
更进一步优选地,所述载体还包括稀释剂和赋形剂中的一种或多种。具体地,所述稀释剂包括淀粉类、糖类、纤维素类和无机盐中的一种或多种。具体地,所述赋形剂包括片剂中的黏合剂、填充剂、润滑剂,半固体制剂软膏剂、霜剂中的基质部分,液体制剂中的防腐剂、抗氧剂、矫味剂、芳香剂、助溶剂、乳化剂、着色剂中的一种或多种。
进一步优选地,所述式(Ⅰ)化合物或其可药用盐或中药益生菌发酵产物的质量分数为10%~90%、15%~85%或30%~80%。
进一步优选地,所述药物或保健品还可以包括第二活性成分。所述第二活性成分根据所述药物或保健品的用途进行选择,在此不作限定。
进一步优选地,所述组合物中所述第二活性成分的质量分数为1%~70%。
优选地,所述保健品或药物的形式包括片剂、胶囊、粉剂、颗粒剂、丸剂、糖浆剂、溶液剂、混悬剂或气雾剂。
优选地,所述保健品的形式还包括、凝胶状或水剂状。
进一步优选地,所述保健品还包括辅料基质,所述辅料基质包括单糖、寡糖、多糖、氨基酸、防腐剂和pH调节剂中的一种或多种。
有益效果:(1)本发明提供了一种全新的式(Ⅰ)化合物、中药益生菌发酵产物及其制备方法;所述的式(Ⅰ)化合物、中药益生菌发酵产物具有优异的具有降胆固醇作用和抗炎作用,可以用于制备药物和保健品(2)试验表明,式(Ⅰ)化合物和中药益生菌发酵产物可减轻三甲胺-N-氧化物引起的高胆固醇血症和炎症,促进粪便总酸性固醇的排泄,降低血浆促炎细胞因子水平,包括白细胞介素IL-1β、IL-6、肿瘤坏死因子α(TNF-α)和单核细胞趋化蛋白1(MCP-1)。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例的附图,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1是本发明式(Ⅰ)化合物的质谱图。
图2是本发明式(Ⅰ)化合物的核磁共振氢谱图。
图3是本发明式(Ⅰ)化合物的核磁共振碳谱图。
图4是本发明中药益生菌发酵产物及式(Ⅰ)结构的单体化合物对相关炎症因子表达的影响。
图5是本发明中药益生菌发酵产物及式(Ⅰ)结构的单体化合物对C57BL/6J小鼠CYP7A1、FXR、SHP、LXRα、HMG-CoA-R、LDL-R、SREBP2表达的影响。
图6是本发明本发明中药益生菌发酵产物及式(Ⅰ)结构的单体化合物对C57BL/6J小鼠NPC1L1、ACAT2、MTP、ABCG5、ABCG8表达的影响。
具体实施方式
下面将结合实施例对本发明技术方案进行清楚、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他实施例,都属于本发明保护的范围。
实施例1式(Ⅰ)化合物的制备
(1)取中药原料30g、益生菌干粉10g于三维混合机中混合至色泽均匀一致,然后加入水50g,在温度为25℃、pH为5.5的条件下发酵24h,得发酵液;
(2)将发酵液于8000r/min离心30min,除去沉淀并保留上清液,对上清液进行冷冻干燥,得粗产物;
(3)将粗产物用色谱技术进行分离,即得式(Ⅰ)化合物;
步骤(1)中所述的中药原料由山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物按重量比1:1:1:1:1:1:1组成(即各提取物用量相等);所述的益生菌干粉由嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉按重量比1:1:1组成;
步骤(3)中所述的色谱技术为制备型HPLC技术;所述的制备型HPLC技术的具体条件为:采用ODS反相色谱柱;选用紫外检测器,检测波长为220nm;以0.1体积%的三氟乙酸水溶液为流动相A,以0.1体积%的三氟乙酸乙腈溶液为流动相B,流动相A:流动相B=88:12;收集13.6~14.1min色谱峰对应的部位,浓缩干燥后即得式(Ⅰ)化合物。
式(Ⅰ)化合物的质谱、氢谱及碳谱数据如下(具体谱图参见图1~3):质谱数据显示,431.2为[M+H]+,分子式为C22H26N2O7.1H NMR(500MHz,DMSO)δ:8.51(td,1H),7.92(d,1H),7.31(m,6H),6.67(m,2H),4.65(m,1H),4.49(m,2H),4.07(d,2H),3.92(s,3H),3.82(s,3H),3.77(m,1H),3.65(s,3H),3.55(m,2H),3.43(s,2H).13C NMR(126MHz,DMSO)δ170.54,169.25,164.26,163.16,158.97,138.25,137.90,132.75,128.27,127.58,127.56,127.48,127.45,114.05,105.79,98.53,72.39,72.26,72.21,69.25,56.10,55.52,54.42,52.43,52.11,51.58,42.64.
经上述质谱、氢谱及碳谱数据解析,可以确定上述方法制备得到了式(Ⅰ)化合物:methyl O-benzyl-N-((2,4-dimethoxybenzoyl)glycyl)serinate。
实施例2式(Ⅰ)化合物的制备
(1)取中药原料300g、益生菌干粉100g于三维混合机中混合至色泽均匀一致,然后加入水500g,超声提取60min;接着在温度为25℃、pH为5.5的条件下发酵30h,得发酵液;
(2)将发酵液于8000r/min离心30min,除去沉淀并保留上清液,对上清液进行冷冻干燥,得粗产物;
(3)将粗产物用色谱技术进行分离,即得式(Ⅰ)化合物;
步骤(1)中所述的中药原料由山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋按重量比1:1:1:1:1:1:1组成(即各提取物用量相等);所述的益生菌干粉由嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉按重量比1:1:1组成;
步骤(3)中所述的色谱技术为制备型HPLC技术;所述的制备型HPLC技术的具体条件为:采用ODS反相色谱柱;选用紫外检测器,检测波长为220nm;以0.1体积%的三氟乙酸水溶液为流动相A,以0.1体积%的三氟乙酸乙腈溶液为流动相B,流动相A:流动相B=88:12;收集13.6~14.1min色谱峰对应的部位,浓缩干燥后即得式(Ⅰ)化合物(质谱、氢谱及碳谱数据与实施例1一致)。
实施例3中药益生菌发酵产物的制备
(1)取中药原料30g、益生菌干粉10g于三维混合机中混合至色泽均匀一致,然后加入水50g,在温度为25℃、pH为5.5的条件下发酵24h,得发酵液;
(2)将发酵液于8000r/min离心30min,除去沉淀并保留上清液,对上清液进行冷冻干燥,得中药益生菌发酵产物;
步骤(1)中所述的中药原料由山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物按重量比1:1:1:1:1:1:1组成(即各提取物用量相等);所述的益生菌干粉由嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉按重量比1:1:1组成。
实施例4中药益生菌发酵产物的制备
(1)取中药原料300g、益生菌干粉100g于三维混合机中混合至色泽均匀一致,然后加入水500g,超声提取60min;接着在温度为25℃、pH为5.5的条件下发酵30h,得发酵液;
(2)将发酵液于8000r/min离心30min,除去沉淀并保留上清液,对上清液进行冷冻干燥,得中药益生菌发酵产物。
步骤(1)中所述的中药原料由山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋按重量比1:1:1:1:1:1:1组成(即各提取物用量相等);所述的益生菌干粉由嗜酸乳杆菌干粉、婴儿双歧杆菌干粉和短双歧杆菌干粉按重量比1:1:1组成。
实验例1
为了评估本发明上述方法制备得到的中药益生菌发酵产物及式(Ⅰ)结构的单体化合物的效果,进行如下效果实验。
(1)动物实验设计:
48只雄性C57BL/6J8周龄小鼠(体重21±24g)。饲养于23℃,12/12h明暗循环,可以自由获取食物和水,适应环境1周后,将动物随机分为4组:正常组(喂养含10%脂肪热量的低脂饲料)、高胆固醇组(喂养1.25%的胆固醇和40%的kcal脂肪的饲料)、发酵产物组(喂养1.25%的胆固醇和40%的kcal脂肪的饲料+100mg/kg中药益生菌发酵产物)、单体化合物组(喂养1.25%的胆固醇和40%的kcal脂肪的饲料+100mg/kg式(Ⅰ)结构的单体化合物)。每周给动物称重。3周时从眶后窦取血,放入肝素微管。6周后动物禁食,麻醉处死。血清、粪便样本(来自结肠)、器官(肝和肠)和脂肪组织(肝、肾、肠、心脏、睾丸和附睾)在使用前采集并储存在-80℃。Elisa试剂盒测定血浆总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和三酰甘油(TG)。Elisa试剂盒测定血浆中炎性细胞因子白细胞介素IL-1β、IL-6、IL-10、TNF-α的含量。
(2)实验结果
正常对照组的小鼠比其他3组的小鼠有更高的食物摄入量(表1)。高胆固醇组小鼠与发酵产物组及单体化合物组小鼠相比,摄食量低,体重增加少。
表1.中药益生菌发酵产物及式(Ⅰ)结构的单体化合物对小鼠食物摄入量以及体重的影响
与正常对照组相比,高胆固醇组小鼠血浆促炎细胞因子IL-6、IL-1β和TNF-α水平显著升高,而抗炎细胞因子IL-10水平降低,说明高胆固醇饮食可引起炎症反应(图4)。而中药益生菌发酵产物及式(Ⅰ)结构的单体化合物可降低血浆促炎细胞因子水平,提示高胆固醇可加重血管炎症,而中药益生菌发酵产物及式(Ⅰ)结构的单体化合物可减轻高胆固醇诱导、加重的炎症。
对小鼠粪便胆固醇分析表明,与正常组饮食相比,高胆固醇饮食显著提高了粪便中胆固醇的总排泄量(表2)。与高胆固醇组相比,发酵产物组及单体化合物组小鼠的胆固醇的排出量较少(表2)。高胆固醇饲喂导致粪便血脂总胆固醇、甘油三酯、高密度脂蛋白胆固醇及排泄量比正常组饮食均有显著性增加(表2)。同时,高胆固醇饲喂显著增加了非高密度脂蛋白胆固醇的排泄量。相反,中药益生菌发酵产物及式(Ⅰ)结构的单体化合物显著降低了血脂总胆固醇、甘油三酯、高密度脂蛋白胆固醇及非高密度脂蛋白胆固醇的排泄量。
表2.中药益生菌发酵产物及式(Ⅰ)结构的单体化合物对小鼠粪便胆固醇排泄的影响
CYP7A1是一种限速酶,它能将胆固醇转化为胆汁酸,以便在肝脏中排出胆汁。Western blotting分析表明,高胆固醇饮食显著上调肝脏CYP7A1的表达。FXR的功能之一是抑制肝脏CYP7A1基因的表达。结果表明,高胆固醇饮食下调FXR蛋白表达。同样,SHP也能抑制胆固醇合成胆汁酸。Western blotting分析发现,高胆固醇饮食降低了SHP的蛋白表达水平。SREBP2和LXRα协同调节胆固醇代谢与胆固醇生物合成和摄取有关的基因,而后者上调胆固醇外排基因LDL-R则是在HMG-CoA-R是调节肝脏胆固醇合成的关键酶。结果表明,高胆固醇饮食诱导了LXRα、HMG-CoA-R、LDL-R和SREBP2的蛋白表达(图5)。而中药益生菌发酵产物及式(Ⅰ)结构的单体化合物处理后显著改善了高胆固醇饮食诱发的相关蛋白的不正常表达,使之表达接近正常组。
胆固醇的吸收需要多种蛋白的参与,如NPC1L1、ACAT2、MTP和ABCG5/8等。NPC1L1是一种固醇转运体,负责将固醇从肠腔转运到肠细胞,而ACAT2则是在MTP将胆固醇装入乳糜微粒前将其酯化。ABCG5/8负责将未被吸收的胆固醇形成的肠细胞释放到肠腔。Westernblotting结果显示高胆固醇饮食下调了NPC1L1、MTP、ACAT2及ABCG5/8的蛋白表达。而中药益生菌发酵产物及式(Ⅰ)结构的单体化合物处理后显著改善了高胆固醇饮食诱发的相关蛋白的不正常表达,使之表达接近正常组(图6)。
上述实验表明式(Ⅰ)化合物和中药益生菌发酵产物具有优异的降胆固醇作用。
以上所揭露的仅为本发明较佳实施例而已,当然不能以此来限定本发明之权利范围,本领域普通技术人员可以理解实现上述实施例的全部或部分流程,并依本发明权利要求所作的等同变化,仍属于发明所涵盖的范围。
Claims (10)
2.权利要求1所述的式(Ⅰ)化合物的制备方法,其特征在于,包含如下步骤:
(1)取中药原料用益生菌进行发酵,得发酵液;
(2)将发酵液进行干燥后得粗产物;
(3)将粗产物用色谱技术进行分离,即得式(Ⅰ)化合物;
步骤(1)中所述的中药原料为包含山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的中药原料;或为包含山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物的中药原料;
步骤(1)中所述的益生菌选自嗜酸乳杆菌、婴儿双歧杆菌、短双歧杆菌中的一种或二种以上的混合。
3.根据权利要求2所述的制备方法,其特征在于,步骤(1)的具体方法为:取中药原料、益生菌干粉以及水混合后,在温度为20~30℃、pH为5~6的条件下发酵16~30h,得发酵液;
所述中药原料、益生菌干粉以及水的重量用量比为:20~40:8~15:40~60。
4.根据权利要求2所述的制备方法,其特征在于,步骤(3)中所述的色谱技术为制备型HPLC技术;所述的制备型HPLC技术的具体条件为:采用反相色谱柱;选用紫外检测器,检测波长为220~230nm;以0.05~0.2体积%的三氟乙酸水溶液为流动相A,以0.05~0.2体积%的三氟乙酸乙腈溶液为流动相B,流动相A:流动相B=88:12;收集13.6~14.1min色谱峰对应的部位,浓缩干燥后即得式(Ⅰ)化合物。
5.一种中药益生菌发酵产物,其特征在于,包含式(Ⅰ)化合物。
6.权利要求5所述的中药益生菌发酵产物的制备方法,其特征在于,包含如下步骤:
(1)取中药原料用益生菌进行发酵,得发酵液;
(2)将发酵液进行干燥后即得所述的中药益生菌发酵产物;
步骤(1)中所述的中药原料为包含山楂、黄芪、丹参、五味子、银杏叶、决明子和马齿苋的中药原料;或为包含山楂提取物、黄芪提取物、丹参提取物、五味子提取物、银杏叶提取物、决明子提取物和马齿苋提取物的中药原料;
步骤(1)中所述的益生菌选自嗜酸乳杆菌、婴儿双歧杆菌、短双歧杆菌中的一种或二种以上的混合。
7.根据权利要求5所述的制备方法,其特征在于,步骤(1)的具体方法为:取中药原料、益生菌干粉以及水混合后,在温度为20~30℃、pH为5~6的条件下发酵16~30h,得发酵液;
所述中药原料、益生菌干粉以及水的重量用量比为:20~40:8~15:40~60。
8.权利要求1所述的式(Ⅰ)化合物或其可药用盐或权利要求6所述的中药益生菌发酵产物在制备药物或保健品中的应用。
9.根据权利要求8所述的应用,其特征在于,所述的药物为具有降胆固醇作用的药物,或为具有抗炎作用的药物;所述的保健品为具有降胆固醇作用的保健品。
10.根据权利要求9所述的应用,其特征在于,所述的药物或保健品含有式(Ⅰ)化合物或其可药用盐或中药益生菌发酵产物和载体;所述式(Ⅰ)化合物或其可药用盐或中药益生菌发酵产物的质量分数为5%~95%。
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CN115137069A (zh) * | 2022-09-06 | 2022-10-04 | 山东向日葵生物工程有限公司 | 一种德氏乳杆菌保加利亚亚种sf-l-18发酵制品及其制备方法和应用 |
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CN112812151A (zh) * | 2021-01-29 | 2021-05-18 | 深圳海创生物科技有限公司 | 一种活性环肽及其在制备具有抗炎作用的产品中的应用 |
CN115137069A (zh) * | 2022-09-06 | 2022-10-04 | 山东向日葵生物工程有限公司 | 一种德氏乳杆菌保加利亚亚种sf-l-18发酵制品及其制备方法和应用 |
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