CN117756890A - 一种脐带间充质干细胞修复大肠菌群的制剂及其制备方法及其在减肥中的应用 - Google Patents
一种脐带间充质干细胞修复大肠菌群的制剂及其制备方法及其在减肥中的应用 Download PDFInfo
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Abstract
本发明涉及一种脐带间充质干细胞修复大肠菌群的制剂及其制备方法及其在减肥中的应用。本发明发现提取的丹参提取物具有较好的降血脂减肥的作用，通过使用该提取物与脐带间充质干细胞提取物一起使用能够有效地改善大肠菌群的组成，提高身体的抗肥胖的效果，可以用于制备减肥药物。具有很好的市场应用价值。
Description
技术领域
本申请涉及生物领域，具体的涉及一种脐带间充质干细胞修复大肠菌群的制剂及其制备方法及其在减肥中的应用。
背景技术
肥胖症是遗传因素与环境因素共同作用所导致的营养代谢障碍性疾病,是慢性疾病发生的主要诱因。它可以诱发与心血管疾病相关的多种代谢功能异常,会增加II型糖尿病、冠心病、中风、充血性心力衰竭、高血压、脂质异常血症、睡眠时呼吸暂停综合症及某些癌症(如卵巢癌、胸腺癌和结肠癌)等的发病率和死亡率。体内脂肪的分布情况在一定程度上决定了人的健康状态,而内脏脂肪分布情况比外周脂肪对人的健康状态影响更大。因此,世界卫生组织将代表内脏脂肪分布情况的“腰围”也作为一个测量指标来评价肥胖症患者合并并发症的可能性:当男性腰围大于94cm、女性腰围大于80cm时,合并并发症的可能性为“一级”;当男性腰围大于102cm、女性腰围大于88cm时,合并并发症的可能性为“二级”。随着世界上许多国家工业化和城市化的程度不断加深,肥胖症的发病率和死亡率也随之不断升高,预防和治疗肥胖症已经成为重要的健康问题。
肥胖的治疗一般是包括几个方面：一个是生活方式的干预，一个是西医药物治疗。生活方式的干预包括体力活动的增加以及控制饮食。有氧运动和无氧运动是指运动时所诱发的肌肉代谢的种类，并取决于运动的类型、强度和持续的时间。体能训练也可以改善心血管的功能，提高运动耐量，以相对较少的耗能来完成一定强度的运动。运动与饮食结合治疗，体重减轻是比较明显的，但如果用极低热卡饮食再加上活动，则难以被肥胖者接受和坚持。活动不仅使体重减轻，而且能使减轻的体重得以保持。运动量和运动的方式因人而异，原则上应采取循序渐进的方式，活动和运动方式应以简单易行为主，结合个人的喜好，活动每消耗335千焦所需的时间来参照医生所给予的表单控制饮食是非常重要的。在此之外，也可以应用比如奥利司他以及其它的减肥药来辅助减轻肥胖症。
但是由于西药本身具有一定的毒副作用，因此开发无毒副作用的药物是研究的重要方向。益生菌通过介导肠道菌群的变化对人类健康产生有益影响。肠道微生物通过发酵分泌生物活性化合物，在肠道黏膜内诱发多种反应，同时影响肝脏和脂肪组织的细胞代谢，从而调节脂质和葡萄糖的体内平衡。肠道菌群也能调节肠道屏障和内分泌功能，影响营养物质转运吸收。故调节肠道菌群是改善和管理肥胖症的有效策略，益生菌的治疗干预可以为肥胖提供新的治疗方法。乳杆菌主要定植于小肠，通过代谢产生乳酸抑制有害细菌繁殖，同时能促进肠道蠕动，具有抗炎等作用。乳杆菌可以通过抑制脂类的合成、吸收，促进胆固醇排出等途径降低血脂从而减重。投向市场的减肥乳杆菌有鼠李糖乳杆菌LPR、加氏乳杆菌BNR17和植物乳杆菌CECT7527等菌株。在加拿大进行的鼠李糖乳杆菌LPR(CGMCC1.3724)菌株饮食干预的临床试验中，肥胖志愿者前12周进行限制热量的饮食摄入，后12周进行体重维持。在第一个12周内，摄人LPR的女性体重减轻显著高于安慰剂组，在第二个12周内，摄入LPR的女性体重继续减轻，而安慰剂组无减轻趋势。男性受试者结果则基本一致，结果表明LPR菌株对肥胖女性有减重作用。PL60菌株在小鼠实验中证实能维持能量摄人不变的同时显著减轻体重。一些研究还发现LGG菌株处理的脂肪饮食小鼠表现为体重增加减少、胰岛素敏感性增强。
大量文献报导，各种组织来源的间充质细胞在各类疾病中有很好的治疗效果。干细胞作为一种具有分泌功能的细胞，其分泌的生物活性分子对不同器官有修复作用。研究发现，脂肪组织来源的CM能够改善利用诱导分化的3T3L1细胞产生的胰岛素抵抗，而且他能通过其分泌的活性物质促进血管生成，对肾脏进行保护，对心脏损伤有抵抗作用。这些结果表明，干细胞来源的条件性培养基对代谢疾病有一个明显的改善作用。通过研究能够发现hAMSCs-CM能够抑制小鼠的饮食性肥胖，hAMSCs-CM主要通过改善胰岛素抵抗还有脂肪组织的过度肥大来抑制小鼠的肥胖。但是目前，针对其他干细胞用于肥胖的治疗研究还不够多。
发明内容
发明人通过研究发现特定的丹参提取物具有一定的降血脂减肥的作用，通过使用该提取物能够有效地改善大肠菌群的组成，提高身体的抗肥胖的效果，可以用于制备减肥药物。
具体的本发明的丹参提取物是采用乙醇抽滤后再经乙酸乙酯萃取后制备的。
具体的，所述制备方法是取丹参粉末，加入30倍体积的70％乙醇(料液比1:30，g/mL)，于40℃，80kHz条件下超声提取，重复两次，每次30min。抽滤所得滤液合并后经旋转蒸发仪减压浓缩，然后加入超纯水重悬，按照体积比1:1用乙酸乙酯进行萃取。将萃取液减压浓缩，得到丹参的乙醇-乙酸乙酯提取物。
更进一步的，将制备的丹参提取物，采用双向凝胶电泳分析并送质谱测序分析，通过分析发现，肽段大部分都集中在10-20个氨基酸序列长度，其中丰度最高的多肽为FWDHIDRKCQNY和IVFNYSRGWDFNN。多肽FWDHIDRKCQNY和IVFNYSRGWDFNN基本保持了与丹参提取物类似的功效。
具体的，本发明提供了丹参的乙醇-乙酸乙酯提取物在制备用于恢复肠道微生物菌群结构减少肝脏脂肪堆积的减肥药物组合物中的用途。
进一步的，本发明还提供了脐带间充质干细胞培养物在制备用于减少肝脏脂肪堆积的减肥药物组合物中的用途。
所述的脐带间充质干细胞培养物是将第3代脐带间充质干细胞细胞接种到含有50ng/mLEGF、10%FBS-DMEM的培养基中培养获得的上清液，上清液留取后迅速转移至液氮内，然后转移至-80℃低温冰箱，将-80℃冻存凝固的上清液抽真空，升华干燥，除去冰晶，最后制得脐带间充质干细胞培养物，-20℃保存。
进一步的，可将药物组合物配制成液体或固体形式以用于口服、肠胃外(包括皮下)或其它途径给药。优选口服给予依帕列净。若适宜，则制剂宜呈不连续的剂量单元，且可由药物领域中熟知的任何方法制备。所有方法均包括以下步骤：将活性成份与一种或多种药学上可接受的赋形剂，如载体(例如液体载体或细粉状固体载体或两者)或稀释剂混合，且接着在适当时将产品成形为所需制剂。
药物组合物及剂型，优选包含一种或多种药学上可接受的赋形剂。优选赋形剂必须是“可接受的”，意思是指与制剂的其它成分相容且对其接受者无害。药学上可接受的载体的实例为本领域技术人员所知的。
具体的本发明的赋形剂可以是例如甘露醇、山梨醇、木糖醇、蔗糖、碳酸钙、磷酸钙、乳糖、交联羧甲基纤维素钠盐(羧甲基醚纤维素钠盐，经交联)、交聚维酮、羟基乙酸淀粉钠、羟丙基纤维素(低取代的)、玉米淀粉、聚乙烯基吡咯烷酮、乙烯基吡咯烷酮与其他乙烯基衍生物的共聚物(共聚维酮)、羟丙基纤维素、羟丙基甲基纤维素、微晶纤维素或淀粉、硬脂酸镁、硬脂酰基富马酸钠、滑石、羟丙基甲基纤维素、羧甲基纤维素、乙酸邻苯二甲酸纤维素、聚乙酸乙烯酯、水、水/乙醇、水/甘油、水/山梨醇、水/聚乙二醇、丙二醇、十六烷基硬脂醇、羧甲基纤维素或脂肪物质(例如，硬脂肪)或其适宜的混合物。
进一步的，赋形剂还可以包括例如选自以下的至少一种化合物：防腐剂、软化剂、乳化剂、表面活性剂、湿润剂、增稠剂、调节剂、磨褪剂(matte finishingagent)、稳定剂、抗氧化剂、组织形成剂(texturizer)、光亮剂、成膜剂、增溶剂、色素、染料、香料和防晒剂。这些赋形剂优选选自氨基酸及其衍生物、聚甘油类、酯类、聚合物和纤维素衍生物、羊毛脂衍生物、磷脂类、乳铁蛋白、乳过氧化物酶、基于蔗糖的稳定剂、E维生素及其衍生物、天然和合成蜡、植物油、甘油三酯、不皂化物、植物固醇类、植物酯类、硅氧烷及其衍生物、蛋白水解产物、荷荷芭油及其衍生物、脂溶性/水溶性酯、甜菜碱类、胺化物、植物提取物、蔗糖酯类、二氧化钛、甘氨酸、对羟苯甲酸酯，更优选丁二醇、硬脂醇聚醚-2、硬脂醇聚醚-21、乙二醇-15硬脂酰醚、棕榈油(cetearyl alcohol)、苯氧乙醇、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯、丁二醇、天然生育酚、丙三醇、二羟基十六烷基磷酸钠、羟基十六烷基异丙醚、硬脂酸乙二醇酯、三异壬酸甘油酯(triisononanoin)、椰油酸辛酯、聚丙烯酰胺、异链烷烃、聚乙二醇单十二醚-7、卡波姆、丙二醇、甘油、没药醇、二甲聚硅氧烷、氢氧化钠、PEG 30-二聚羟基硬脂酸、癸酸/辛酸甘油三酯、鲸蜡硬脂醇辛酸酯(cetearyl octanoate)、己二酸二丁酯、葡萄籽油、荷荷芭油、硫酸镁、EDTA、环聚二甲基硅氧烷、黄原胶、柠檬酸、十二烷基硫酸钠、矿物蜡和矿物油、异硬脂醇异硬脂酸酯、丙二醇二壬酸、丙二醇异硬脂酸酯、PEG 8蜂蜡、氢化棕榈油甘油酯、羊毛脂油、芝麻油、鲸蜡醇乳酸酯、羊毛脂醇、蓖麻油、二氧化钛、乳糖、蔗糖、低密度聚乙烯和等渗盐溶液。
举例而言，片剂可通过混合该活性物质(单种或多种)与一种或多种赋形剂并随后将其压制而获得。该片剂也可由若干层构成。赋形剂的实例为：惰性稀释剂，例如甘露醇、山梨醇、木糖醇、蔗糖、碳酸钙、磷酸钙和乳糖；崩解剂，例如交联羧甲基纤维素钠盐(羧甲基醚纤维素钠盐，经交联)、交聚维酮、羟基乙酸淀粉钠、羟丙基纤维素(低取代)和玉米淀粉；粘结剂，例如聚乙烯基吡咯烷酮、乙烯基吡咯烷酮与其他乙烯基衍生物的共聚物(共聚维酮)、羟丙基纤维素、羟丙基甲基纤维素、微晶纤维素或淀粉。
药物组合物可配制为以下形式：溶液、混悬液、乳剂、片剂、颗粒剂、细颗粒剂、散剂、胶囊、小胶囊、软胶囊、丸剂、口服溶液、糖浆、干糖浆、咀嚼片、糖衣片、泡腾片、滴剂、速溶片、口服快速分散片等。根据本发明的一个优选实施方案，提供了一种用于口服给药的固体药物组合物。优选的药物剂型为片剂或胶囊。
药物组合物和剂型可以各种不同的方式包装。通常地，分配的产品和物件包括以适当形式含有一种或多种药物剂型的一种或多种容器。片剂典型包装在易于处置、分配和保存的合适内包装内，且在保存期间与环境长时间接触时确保组合物的适当稳定性。片剂的内包装可为瓶或泡罩包装。
应当理解，欲向患者给予且在根据本发明的治疗或预防中需要使用的根据本发明的药物组合物的量将随给药途径、需要治疗或预防的病症的性质及严重程度、患者年龄、体重及身体状况、伴随药物而变化，且最终将由住院医生决定。然而，一般而言，本发明的药物组合物或剂型中所包括的本发明的药物的量足以在其与一种或多种减肥药组合给予时改善待治疗患者的血脂控制。此外，一般而言，本发明的药物组合物或剂型中所包括的本发明的一种或多种减肥药的量足以在其给予时改善待治疗患者的体重控制。
下文中，描述了根据本发明的药物组合物、药物剂型及治疗中欲使用的依帕列净的量的优选范围。这些范围是指就成人患者(尤其例如体重为约70kg的人)而言每天给予的量，且该范围可根据每日给予2次及其它给药途径及患者年龄相应进行调整。剂量及量的范围依据活性成分计算。优选单身提取物的药物量为1至50mg，更优选为1至25mg，更优选5至25mg。干细胞提取物的优选剂量为，例如1mg、2mg、2.5mg、5mg、7.5mg、10mg、12.5mg、15mg、20mg、25mg和50mg。
具体的，本发明的药物组合物可以调节肠道菌群的组成，使得有益菌群的含量得到提高。
有益效果是本发明通过研究发现提取的丹参提取物以及相应多肽具有较好的降血脂减肥的作用，通过使用该提取物与脐带间充质干细胞提取物一起使用能够有效地改善大肠菌群的组成，提高身体的抗肥胖的效果，可以用于制备减肥药物。具有很好的市场应用价值。
附图说明
图1 丹参提取物对小鼠肝脏重量的影响结果图
图2 脐带间充质干细胞培养物对小鼠肝脏重量的影响结果图
具体实施方式
本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文所述的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。以下实施案例中的方法、设备、材料，如果未进行特别说明，均为本领域常规方法、设备和材料，均可由市场购得。
实施例1 丹参提取物的制备
称取100g丹参粉末，加入30倍体积的70％乙醇(料液比1:30，g/mL)，于40℃，80kHz条件下超声提取，重复两次，每次30min。抽滤所得滤液合并后经旋转蒸发仪减压浓缩，然后加入200mL超纯水重悬，按照体积比1:1用乙酸乙酯进行萃取，萃取重复5次。将萃取液减压浓缩，得到丹参的乙醇-乙酸乙酯提取物合计3.27g，命名为DS提取物，用生理盐水调整浓度为1mg/mL备用。
实施例2 对照1丹参提取物的制备
称取100g丹参粉末，加入30倍体积的70％乙醇(料液比1:30，g/mL)，于40℃，80kHz条件下超声提取，重复两次，每次30min。抽滤所得滤液合并后经旋转蒸发仪减压浓缩，获得对照1丹参提取物5.48g，用生理盐水调整浓度为1mg/mL备用。
实施例3 对照2丹参提取物的制备
称取100g丹参粉末，用1L水溶解，按照100U/g粉末的比例加入木瓜蛋白酶，水解时间4h，灭酶活，离心3000r/min，20min，取上清，减压浓缩，获得对照2丹参提取物2.06g，用生理盐水调整浓度为1mg/mL备用。
实施例4 提取物功效验证
将8周的C57BL/6J 小鼠适应性培养1周后随机分为5组：对照组、模型组和实验组（1-3，分别对应于实施例1-3的提取物），每组10只。饲喂对照组普通低脂饲料（D12450B，重庆市华雅干细胞技术有限公司）、模型组和实验组饲喂脂肪含量60%的高脂饲料（D12492）。饲喂13周，实验组1-3分别对应按照50mg/kg/天剂量灌胃实施例1-3提取物，灌胃模型组和对照组0.1mL生理盐水。
饲喂25周后，用CO2麻醉小鼠并从其心脏取血后解剖小鼠,取出小鼠肝脏， 称重记录，结果如图1所示。
从图1可以看出，与对照组相比，模型组小鼠肝脏重量显著的增加（其肝脏积累了大量脂肪，差异极其显著P<0.01)；实验组1治疗后，肝脏重量和对照组的相比，基本相似，无无明显差异（图1）,说明治疗效果极好。而采用乙醇或者酶解制备的提取物肝脏重量都相对于对照组有明显的提高，这结果表明，结果表明采用乙醇-乙酸乙酯提取方法制备得到的提取物方可有效的缓解肝脏中脂肪的积累。
将收集的血液室温静置1h后，4000g离心15min,收集上层血清，按照试剂盒说明书测定血清中TG、T-CHO、LDL-C和HDL-C含量，结果如表1所示
；
从表1可以看出，模型组相比于对照组血清中的TG、TC、HDL-C和LDL-C含量显著升高（差异极其显著P<0.01)），经过实验组1的治疗后，小鼠血清中的TG、TC、HDL-C和LDL-C含量显著降低，具有较好的降低血脂蛋白的效果；实验组2相比于实验组1在效果上虽然有，但是有一定差异，实验组3基本没有降血脂的效果，这说明不同的提取方法对于疗效具有显著的影响。以上结果表明，表明乙醇-乙酸乙酯提取物能明显改善高脂饮食引发的脂质代谢紊乱。
实施例5 脐带间充质干细胞培养物的制备
获得脐带组织，将脐带组织用含有双倍双抗的PBS漂洗，把血块洗净。将脐带组织剪成3-5cm小段。横向夹住脐带组织，明显可见2条脐动脉和1条脐静脉。纵向剖开脐带，露出血管，将血管从周围组织分离出来。将脐带组织漂洗干净，用眼科剪将组织剪碎。加入质量／体积比为0.1％的II型胶原酶至完全覆盖组织块，置于培养箱内持续消化6h，100目筛网过滤收集细胞；生理盐水冲洗细胞3次，每次2000rpm，8min；用含10％FBS的DMEM／F12培养液重悬细胞，调整细胞密度为1x106cells／ml，接种于T-25培养瓶中，置于37摄氏度饱和湿度、5％C02培养箱内培养；3天后全量换为MesenPRO RS Medium培养液，弃去未贴壁的细胞与杂质，以后根据细胞生长情况，每3天换液一次。
取第三代培养细胞，采用细胞标志物检测试剂盒进行鉴定，结果显示，分离制备的脐带间充质干细胞针对标志物CD73、CD90和CD105，其阳性率均高于96％，针对表面标志物CD11b、CD14、CD19、CD34、CD45和HLA-DR的阳性率均低于3％，这说明分离制备得到了脐带间充质干细胞。
将第3代细胞接种到含有50ng/mLEGF、10%FBS-DMEM的培养基中，扩增至5×108，留取扩增期间所有上清液，上清液留取后迅速转移至液氮内，然后转移至-80℃低温冰箱，将-80℃冻存凝固的上清液抽真空，升华干燥，除去冰晶，最后制得冻干粉，－20℃保存。使用前用生理盐水溶解，0.22μm过滤器过滤，调整浓度为0.5mg/mL备用。
实施例6 脐带间充质干细胞培养物对小鼠肥胖的功效验证
取8周的C57BL/6J雄性小鼠适应性培养1周后进行体重称量分组，然后分别给予正常饮食及高脂饮食HFD（60%脂肪）喂养，喂养至第13周。实验分组：1.正常饮食组(对照组)；2.高脂饮食组(模型组)；3.治疗实验组，每组小鼠10只，其中非治疗实验组同期灌胃DMEM作为药物溶剂对照。
治疗实验组1-2分别对应按照100mg/kg/天和250mg/kg/天剂量灌胃脐带间充质干细胞培养物。
饲喂25周后，用CO2麻醉小鼠后解剖小鼠,取出小鼠肝脏， 称重记录，结果如图2所示。
从图2可以看出，脐带间充质干细胞培养物具有剂量依赖性的降低高脂饮食带来的肝脏重量增加的效果与模型组相比差异及其显著（P<0.01），肝脏重量降低1倍还多，说明脐带间充质干细胞培养物具有减肥的效果。
此外， 取小鼠腹部脂肪组织 HE 染色， 结果显示与模型组相比，治疗实验组的脂肪细胞明显减小，而且剂量越高，缩小约明显。
实施例7 脐带间充质干细胞培养物以及丹参提取物对小鼠肠道菌群的影响
将C57 BL/6J 小鼠适应性培养1周后随机分为4组：空白对照组、模型组和实验组（A-B），每组10只。饲喂对照组普通低脂饲料、模型组和实验组饲喂脂肪含量60%的高脂饲料。饲喂13周，实验组A按照50mg/kg/天剂量灌胃实施例1提取物同时还灌胃100mg/kg/天实施例4制备的脐带间充质干细胞培养物；
实验组B按照50mg/kg/天剂量灌胃lifespaceb420塑形益生菌(阳性对照)；
灌胃模型组和空白对照组0.1mL生理盐水。
饲喂小鼠22周后，收集其粪便，进行GC-MS/MS 分析各组小鼠粪便短链脂肪酸含量的影响。结果如表2所示
；
从表2可以看出，与对照组相比，模型组小鼠的粪便中乙酸、丙酸、丁酸、戊酸、异丁酸含量较低，而己酸、异戊酸明显高于对照组；相较于模型组小鼠，实验组A小鼠粪便中各种酸的含量均得到明显的改善，向对照组接近；实验组B阳性对照的改善效果与实验组A相比还有一定改善的空间，这说明本发明的脐带间充质干细胞培养物以及丹参提取物可以对小鼠肠道菌群进行营养和改善能够有效的促进有益菌群的恢复。
将治疗后的每组的小鼠排便后用灭菌的镊子夹取小鼠粪便，样本通常需 1g 左右，样本采集后立刻放入-80℃冰箱进行低温保存，委托微基生物对粪便样品进行宏基因组测序分析，结果发现，脐带间充质干细胞培养物以及丹参提取物能提高肥胖小鼠的肠道菌群总丰度，使肥胖小鼠在肠道菌群结构上与对照组健康小鼠相似；其中双歧杆菌属、别样杆菌属以及厌氧菌属的丰度得到显著的提高明显改善了小鼠肠道菌群的代谢功能。而实验组B中双歧杆菌属和厌氧菌属的丰度得到明显的提高，但是于实验组A相比，菌群总丰度还有较大的差距，这些菌群上的差异，导致最终产酸、降脂效果有一定差距。
实施例8 提取物成分鉴定
将实施例1制备的丹参提取物，采用双向凝胶电泳分析。等点聚焦用11cmIPG预制胶条。丹参提取物冻干样品1mg溶解于800μL水化缓冲液(0.2％Bio-Lyte3/10ampho两性电解质，0.001％溴酚蓝)，胶内被动水化上样，胶条溶胀时间18h。等点聚焦时长为30O00V hr，胶条依次在平衡液1和平衡液2中震荡浸润15min后转入16％分离胶，20mA恒定电流30min，25mA恒定电流继续电泳9h。电泳结束后迅速剥离凝胶，置于考马斯亮蓝染色液中，凝胶脱色至背景清晰后放入EXQuest spot cutter切胶系统，选取显色清晰的胶点切割并送质谱测序分析，通过分析发现，肽段大部分都集中在10-20个氨基酸序列长度，其中丰度最高的多肽为FWDHIDRKCQNY和IVFNYSRGWDFNN。将所述二个多肽进行人工合成后，按照实施例4的提取物功效验证中相同的方法和用量进行检测后发现，多肽FWDHIDRKCQNY和IVFNYSRGWDFNN基本保持了与丹参提取物类似的功效，经过二个多肽分别的治疗后，小鼠血清中的TG、TC、HDL-C和LDL-C含量分别都得到了显著降低（与实施例1的丹参提取物效果整体上基本相似，但是在低密度脂蛋白的治疗效果分别达到了2.21±0.17和2.08±0.12，比丹参提取物的2.35±0.26效果还要好），这说明多肽为FWDHIDRKCQNY和IVFNYSRGWDFNN具有相应的调节血脂的功效。
当对本发明的实施方式进行实施或试验时，可以使用与本说明书中记载的方法和材料类似或等同的任选的方法和材料，本说明书中记载了优选的方法、装置、材料。然而，在记载本发明的材料与方法之前，应当理解为，可以按照常规的实验方法以及最优化的目的来改变本说明书中记载的特定的大小、形状、尺寸、材料、方法、手段等，因此本发明不限于这些。并且应当理解为，本说明书中使用的专业术语仅用于说明特定的类型或实施方式，并不用于限制本发明的范围，本发明的范围仅受添附的权利要求的范围的限制。
Claims (6)
1.一种调节血脂功能的多肽，其特征在于氨基酸序列如FWDHIDRKCQNY或IVFNYSRGWDFNN所示。
2.一种用于减肥的药物组合物，其特征在于由丹参的乙醇-乙酸乙酯提取物和脐带间充质干细胞培养物组成；其中丹参的乙醇-乙酸乙酯提取物的制备方法是取丹参粉末，加入30倍体积的70％乙醇，料液比1:30，g/mL，于40℃，80kHz条件下超声提取，重复两次，每次30min。抽滤所得滤液合并后经旋转蒸发仪减压浓缩，然后加入超纯水重悬，按照体积比1:1用乙酸乙酯进行萃取；将萃取液减压浓缩，得到丹参的乙醇-乙酸乙酯提取物；脐带间充质干细胞培养物是将脐带间充质干细胞在培养基中培养后得到的上清液冻干后制备获得的；所述丹参提取物和脐带间充质干细胞培养物的质量比为1：2。
3.一种用于减肥的药物组合物，其特征在于有效成分为丹参提取物；其中丹参提取物的制备方法是取丹参粉末，加入30倍体积的70％乙醇，料液比1:30，g/mL，于40℃，80kHz条件下超声提取，重复两次，每次30min。抽滤所得滤液合并后经旋转蒸发仪减压浓缩，然后加入超纯水重悬，按照体积比1:1用乙酸乙酯进行萃取；将萃取液减压浓缩，得到丹参的乙醇-乙酸乙酯提取物。
4.丹参的乙醇-乙酸乙酯提取物在制备用于恢复肠道微生物菌群结构减少肝脏脂肪堆积的减肥药物组合物中的用途；其中，丹参的乙醇-乙酸乙酯提取物的制备方法是取丹参粉末，加入30倍体积的70％乙醇，料液比1:30，g/mL，于40℃，80kHz条件下超声提取，重复两次，每次30min。抽滤所得滤液合并后经旋转蒸发仪减压浓缩，然后加入超纯水重悬，按照体积比1:1用乙酸乙酯进行萃取；将萃取液减压浓缩，得到丹参的乙醇-乙酸乙酯提取物。
5.丹参的乙醇-乙酸乙酯提取物和脐带间充质干细胞培养物在制备用于恢复肠道微生物菌群结构减少肝脏脂肪堆积的减肥药物组合物中的用途；其中，丹参的乙醇-乙酸乙酯提取物的制备方法是取丹参粉末，加入30倍体积的70％乙醇，料液比1:30，g/mL，于40℃，80kHz条件下超声提取，重复两次，每次30min。抽滤所得滤液合并后经旋转蒸发仪减压浓缩，然后加入超纯水重悬，按照体积比1:1用乙酸乙酯进行萃取；将萃取液减压浓缩，得到丹参的乙醇-乙酸乙酯提取物；脐带间充质干细胞培养物是将脐带间充质干细胞在培养基中培养后得到的上清液冻干后制备获得的；所述丹参提取物和脐带间充质干细胞培养物的质量比为1：2。
6.如权利要求4或5所述的用途，其特征在于药物组合物还含有药学上可接受的载体。
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