CN116549611A - 一种治疗动脉粥样硬化的干细胞药物 - Google Patents
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Abstract
本发明涉及药物制剂技术领域，具体涉及一种治疗动脉粥样硬化的干细胞药物，包括干细胞、人血白蛋白、佛手提取物、***龙、维生素C、溶媒。本发明所述干细胞药物治疗动脉粥样硬化的机制主要是参与新生血管形成、启动和分泌相关因子，整合受损血管，诱导生成血管内皮细胞、平滑肌细胞，促进局部新生血管形成、神经再生和重构等，改善微循环，降低血清胆固醇含量，减少斑块面积，实现促进创面愈合，达到治疗的目的。
Description
技术领域
本发明涉及药物制剂技术领域，具体涉及一种治疗动脉粥样硬化的干细胞药物及其制备方法。
背景技术
动脉粥样硬化(atherosclerosis,AS)是由于脂质成分和炎性物质沉积在动脉血管内壁，形成外观像小米粥样的斑块，导致动脉变窄***、弹性降低、阻碍血流，继而造成器官缺血损伤。一旦发展到血栓严重阻塞动脉腔时，则该动脉所供应的组织或器官将缺血或坏死，会诱发严重疾病，包括冠心病(心绞痛、心肌梗死)、脑卒中以及外周血管疾病。
由于临床使用的抗AS药物存在肝肾损伤、横纹肌溶解等副作用，如何攻克它成为临床医学的研究重点。细胞疗法为治疗动脉粥样硬化提供了一种创新的方法。
干细胞具有调节血脂水平、抑制炎症、修复受损组织和支持造血的功能，对血管损伤、血管炎症具有有益的修复调节作用。越来越多的研究表明干细胞具有修复损伤组织的潜能，干细胞技术的发展为损伤血管修复提供了新方向。
CN 114231484A涉及一种ApoB抗原特异性间充质干细胞的制备方法及其产品和应用。ApoB抗原是动脉粥样硬化核心抗原，创建了抗原特异性WJMSCs，精准靶点抑制动脉粥样硬化(AS)免疫微环境中致病免疫细胞，从病因学上首次达到针对AS特异病理机制靶点干预之目标。
CN115120619A提供了一种肌肉干细胞在预防、缓解和治疗心血管疾病中的用途。实验表明，在动脉粥样硬化小鼠尾静脉注射肌肉干细胞能显著延缓小鼠的动脉粥样硬化进程，有效减少主动脉弓及颈动脉分支处斑块面积，减少体内白色脂肪组织，降低小鼠机体炎症反应等。此外，还提供一种肌肉干细胞对于动脉粥样硬化的预防和治疗方法。
发明内容
针对现有技术中治疗动脉粥样硬化的制剂或方法存在细胞类型单一、不能充分发挥干细胞的生物学性，不利于疾病治疗等问题，本发明提供一种治疗动脉粥样硬化的干细胞药物及其制备方法。
本发明采用如下技术方案：
一方面，本发明提供一种治疗动脉粥样硬化的干细胞药物，包括干细胞、人血白蛋白、佛手提取物、***龙、维生素C、溶媒。
进一步地，所述溶媒为生理盐水或PBS缓冲液或无菌水。
进一步地，所述干细胞的浓度为0.25×105-1.5×107个/mL。
进一步地，所述干细胞为间充质干细胞。进一步地，所述间充质干细胞为骨髓间充质干细胞、脐带间充质干细胞、脂肪间充质干细胞、牙髓间充质干细胞中的一种或多种。
进一步地，所述佛手提取物的浓度为1～5％。佛手提取物以芸香科植物佛手的果实为原料经过回流提取、减压浓缩、喷雾干燥而成的水溶性棕色粉末状产品，有效保留了佛手原有的植物有效成分。
进一步地，所述***龙的浓度为1～5％。
进一步地，所述维生素C的浓度为0.1～0.75％。
进一步地，所述人血白蛋白的浓度为0.2～0.25％。
进一步地，所述干细胞药物为静脉注射剂。
另一方面，本发明提供一种治疗动脉粥样硬化的干细胞药物的制备方法，包括如下步骤：
S1干细胞的分离培养：分离干细胞后，接种于含有10％胚胎牛血清的a-MEM培养基中，置于CO2培养箱中培养，干细胞融合度为85％以上时采用0.2％胰酶消化传代；
S2分散介质的制备：按照质量体积比将人血白蛋白、佛手提取物、***龙、维生素C，用溶媒配制后得分散介质，0-4℃预冷备用；
S3干细胞药物的制备：将S1的干细胞消化计数后，用分散介质悬浮干细胞，调整干细胞浓度为0.25×105-1.5×107个/mL，即得。
进一步地，S1中培养时间为24-48小时。
另一方面，本发明所述的干细胞药物在制备心血管类疾病药物中的用途，优选地，所述心血管类疾病为动脉粥样硬化、心肌梗塞等。
与现有技术相比，本发明具有如下的有益效果：
佛手提取物能够高效的舒张气道平滑肌，能降低胆固醇，改善脂质代谢，促进干细胞输注过程中血管内皮细胞和平滑肌细胞舒张，降低了细胞聚集而被输液滤器过滤导致的细胞损失。
在动脉粥样硬化局部过表达的ROS和丰富脂质微环境下，抗炎药物***龙的存在可移除脂质，实现抗炎去脂效果。
人血白蛋白为临床注射液成分，可为细胞提供营养，利于细胞的新陈代谢，维生素C的添加可维持各种过氧化酶的活性，也有利于细胞代谢和活性的保持。
本发明所述干细胞药物治疗动脉粥样硬化的机制主要是参与新生血管形成、启动和分泌相关因子，整合受损血管，诱导生成血管内皮细胞、平滑肌细胞，促进局部新生血管形成、神经再生和重构等，改善微循环，降低血清胆固醇含量，减少斑块面积，实现促进创面愈合，达到治疗的目的。
具体实施方式
下面结合具体实施例，进一步阐述本发明。这些实施例仅用于说明本发明而不用于限制本发明的范围。
实施例1
脐带间充质干细胞的分离培养：
将获取的新鲜脐带中多余废弃液起到，用75％酒精消毒后取出，加入PBS漂洗2次洗去酒精。用组织剪将脐带剪成小段，每段纵向剪开，去除脐带内三根血管(两条动脉，一条静脉)，同时去除脐带外膜。将分离好的脐带用剪成约1mm3大小的组织块，取适量放入直径为10cm的无菌培养皿中，覆盖70％培养皿的底面积。加入LONZA人干细胞无血清培养液(Lonza UltraCULTURETM)，5％CO2、37℃、饱和湿度为95％的CO2培养箱中培养。第5-7天半量换培养基，继续培养12-14天左右全量换液去掉组织块同时收集细胞传代培养。
分离出生长状态良好的脐带间充质干细胞后，按照6000～8000/cm2的密度接种于含有10％胚胎牛血清的a-MEM培养基中，置于CO2培养箱中培养24-48小时，干细胞融合度为85％以上时，细胞生长状态良好，采用0.2％胰酶消化，回收全部细胞，并用生理盐水清洗细胞2～3次，得到间充质干细胞。
实施例2
1)分散介质的制备：按照质量体积比将人血白蛋白、佛手提取物、***龙、维生素C，用溶媒配制后得分散介质，0-4℃预冷备用，所述佛手提取物的浓度为1％，所述***龙的浓度为5％，所述维生素C的浓度为0.1％，所述人血白蛋白的浓度为0.25％；
2)干细胞药物的制备：将实施例1获得的间充质干细胞消化计数后，用分散介质悬浮干细胞，调整干细胞浓度为0.25×105个/mL，即得。
所述干细胞药物为静脉注射剂。
实施例3
1)分散介质的制备：按照质量体积比将人血白蛋白、佛手提取物、***龙、维生素C，用溶媒配制后得分散介质，0-4℃预冷备用，所述佛手提取物的浓度为5％，所述***龙的浓度为1％，所述维生素C的浓度为0.75％，所述人血白蛋白的浓度为0.2％；
2)干细胞药物的制备：将实施例1获得的间充质干细胞消化计数后，用分散介质悬浮干细胞，调整干细胞浓度为1.5×107个/mL，即得。
所述干细胞药物为静脉注射剂。
实施例4
1)分散介质的制备：按照质量体积比将人血白蛋白、佛手提取物、***龙、维生素C，用溶媒配制后得分散介质，0-4℃预冷备用，所述佛手提取物的浓度为2.5％，所述***龙的浓度为3％，所述维生素C的浓度为0.5％，所述人血白蛋白的浓度为0.23％；
2)干细胞药物的制备：将S1获得的间充质干细胞消化计数后，用分散介质悬浮干细胞，调整干细胞浓度为1×106个/mL，即得。
所述干细胞药物为静脉注射剂。
实施例5
将本申请实施例2-4制备的静脉注射剂用于大鼠动脉粥样硬化模型的干预治疗。显示可有效调节脂质代谢水平，再生和修复血管内皮，消除炎症，提高斑块稳定性，提高血管修复功能，能有效治疗动脉粥样硬化。
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，尽管参照前述实施例对本发明进行了详细的说明，对于本领域的技术人员来说，其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换。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)
1.一种治疗动脉粥样硬化的干细胞药物，其特征在于，包括干细胞、人血白蛋白、佛手提取物、***龙、维生素C、溶媒。
2.根据权利要求1所述干细胞药物，其特征在于，所述溶媒为生理盐水或PBS缓冲液或无菌水。
3.根据权利要求1所述干细胞药物，其特征在于，所述干细胞的浓度为0.25×105-1.5×107个/mL；
所述干细胞为间充质干细胞。
4.根据权利要求3所述干细胞药物，其特征在于，所述间充质干细胞为骨髓间充质干细胞、脐带间充质干细胞、脂肪间充质干细胞、牙髓间充质干细胞中的一种或多种。
5.根据权利要求1所述干细胞药物，其特征在于，所述佛手提取物的浓度为1～5％；所述***龙的浓度为1～5％。
6.根据权利要求1所述干细胞药物，其特征在于，所述维生素C的浓度为0.1～0.75％；
所述人血白蛋白的浓度为0.2～0.25％。
7.根据权利要求1所述干细胞药物，其特征在于，所述干细胞药物为静脉注射剂。
8.一种权利要求1～7任一项所述治疗动脉粥样硬化的干细胞药物的制备方法，包括如下步骤：
S1干细胞的分离培养：分离干细胞后，接种于含有10％胚胎牛血清的a-MEM培养基中，置于CO2培养箱中培养，干细胞融合度为85％以上时采用0.2％胰酶消化传代；
S2分散介质的制备：按照质量体积比将人血白蛋白、佛手提取物、***龙、维生素C，用溶媒配制后得分散介质，0-4℃预冷备用；
S3干细胞药物的制备：将S1的干细胞消化计数后，用分散介质悬浮干细胞，调整干细胞浓度为0.25×105-1.5×107个/mL，即得。
9.根据权利要求8所述干细胞药物的制备方法，其特征在于，S1中培养时间为24-48小时。
10.一种权利要求1-7任一项所述的干细胞药物在制备心血管类疾病药物中的用途，优选地，所述心血管类疾病为动脉粥样硬化、心肌梗塞等。
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