CN116832064A - 用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体组合物、制备方法及其应用 - Google Patents
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Abstract
本发明属于生物医药技术领域,公开了一种用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物、制备方法及其应用,鼻内给药外泌体混合物包括源自神经干细胞的外泌体、源自间充质干细胞的外泌体以及载体;鼻内给药外泌体混合物每毫升中至少含有2×109个外泌体。源自神经干细胞的外泌体和源自间充质干细胞的外泌体的体积比为1:1。使用源自神经干细胞和间充质干细胞的外泌体组合物进行鼻内递送,利用鼻腔独特的解剖和生理特征,可以绕过血脑屏障,允许直接进入大脑。外泌体可以赋予神经保护和刺激再生,从而潜在地减轻阿尔茨海默病和痴呆症的症状和进展。
Description
技术领域
本发明属于生物医药技术领域,具体涉及一种用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物、制备方法及其应用。
背景技术
随着老龄化时代的到来,老年痴呆症成为世界范围内的重负。阿尔茨海默氏病(AD)并不等于痴呆症,或者说它只是其中一个分支。AD是一种隐匿的进行性发展的神经系统退行性疾病。临床上以记忆障碍、失语、失用、失认、视空间技能损害、执行功能障碍以及人格和行为改变等全面性痴呆表现为特征,病因迄今未明。它可能是由于当某些蛋白质在脑细胞内外积累过多时造成脑细胞彼此难以维系健康良好的沟通,导致了神经细胞之间丧失连接,最终造成神经细胞死亡和脑组织功能丧失。阿尔茨海默氏病现如今也不仅仅只出现在老人身上,甚至有一小部分年轻人也会患这种病。由于其具体的病因尚不明确,目前对于这种疾病的治疗成效很低。同时,目前的给药方法难以通过血脑屏障,限制了治疗效果。
发明内容
本发明旨在至少在一定程度上解决上述技术问题。为此,本发明第一目的在于提供一种用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物。
为实现第一目的,本发明所采用的技术方案为:
一种用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物,包括源自神经干细胞的外泌体、源自间充质干细胞的外泌体以及载体;鼻内给药外泌体混合物每毫升中至少含有2×109个外泌体。神经干细胞通常是从哺乳动物脑组织中获得的,它们以自我更新和分化为各种类型神经细胞的能力而闻名,它们的外泌体被认为携带神经保护和再生分子。间充质干细胞可以从胚胎组织或其他合适的来源获得,其外泌体具有抗炎特性。来自神经干细胞和间充质干细胞的外泌体已知携带神经保护和再生分子。当经鼻给药时,这些分子可以到达脑细胞,在那里它们可以通过促进神经修复,减少炎症和防止进一步的神经元变性来发挥作用。
优选地,源自神经干细胞的外泌体和源自间充质干细胞的外泌体的体积比为1:1,此比例提供了两种外泌体最佳的协同效应,向脑细胞提供神经保护和再生分子,减少炎症,并防止与阿尔茨海默病和痴呆症相关的进一步退化。
优选地,所述鼻内给药外泌体混合物制成喷雾剂。
优选地,所述载体为水或生理盐水。
本发明第二目的在于提供一种用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物的制备方法。
为实现第二目的,本发明所采用的技术方案为:
一种用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物的制备方法,包括以下步骤:
将神经干细胞和间充质干细胞分别培养并传代四次;收获培养基,将培养基中的外泌体分离,分别得到源自神经干细胞的外泌体和源自间充质干细胞的外泌体;将获得的两种外泌体混合在载体中得到鼻内给药外泌体混合物。
优选地,采用超离心法将外泌体从培养基中分离,确保获得高纯度的外泌体,并使用纳米颗粒跟踪分析(NTA)测定外泌体的浓度。
本发明第三目的在于提供一种鼻内给药外泌体混合物在预防和治疗阿尔茨海默病和痴呆症中的应用。
本发明的有益效果为:
本发明所提供的用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物,使用源自神经干细胞和间充质干细胞的外泌体组合物进行鼻内递送,利用鼻腔独特的解剖和生理特征,可以绕过血脑屏障,允许直接进入大脑。外泌体可以赋予神经保护和刺激再生,从而潜在地减轻阿尔茨海默病和痴呆症的症状和进展。
相较于现有技术,本发明为控制和预防阿尔茨海默病和痴呆症提供了一种新的治疗方法,解决了现有治疗方法在穿越血脑屏障方面的局限性。同时,由于神经干细胞可以从患者自身的脑组织中提取,因此有可能开发出个性化的治疗方法,这可能会提高治疗效果并减少潜在的副作用。
具体实施方式
下面结合具体实施例对本发明做进一步阐释。需要说明的是,在不冲突的情况下,本发明中的实施例及实施例中的特征可以相互组合。
应该指出,以下详细说明都是示例性的,旨在对本发明提供进一步的说明。除非另有指明,本文使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解的相同含义。
需要注意的是,这里所使用的术语仅是为了描述具体实施方式,而非意图限制根据本发明的示例性实施方式。如在这里所使用的,除非上下文另外明确指出,否则单数形式也意图包括复数形式,此外,还应当理解的是,当在本说明书中使用术语“包含”和/或“包括”时,其指明存在特征、步骤、操作、器件、组件和/或它们的组合。
本实施例提供一种用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物,包括源自神经干细胞的外泌体、源自间充质干细胞的外泌体以及载体水;鼻内给药外泌体混合物每毫升中至少含有2×109个外泌体。源自神经干细胞的外泌体和源自间充质干细胞的外泌体的体积比为1:1。该鼻内给药外泌体混合物通过鼻内施用,利用鼻喷雾剂或其他合适的给药技术,确保有效成分直接进入大脑,绕过血脑屏障。
上述的鼻内给药外泌体混合物的制备方法,包括以下步骤:
将神经干细胞和间充质干细胞分别培养并传代四次;收获培养基,采用超离心法将将培养基中的外泌体分离,分别得到源自神经干细胞的外泌体和源自间充质干细胞的外泌体,将获得的两种外泌体混合在载体中得到鼻内给药外泌体混合物。
上述的鼻内给药外泌体混合物在预防和治疗阿尔茨海默病和痴呆症中的应用。鼻内给药组合物被制成喷雾剂,将含有外泌体的溶液喷入鼻腔,确保鼻腔内外泌体的最佳递送和吸收,并将其运输到大脑,从而对中枢神经系统疾病产生潜在的预防和治疗作用。
本发明不局限于上述可选的实施方式,任何人在本发明的启示下都可得出其他各种形式的产品。上述具体实施方式不应理解成对本发明的保护范围的限制,本发明的保护范围应当以权利要求书中界定的为准,并且说明书可以用于解释权利要求书。
Claims (7)
1.一种用于预防和治疗阿尔茨海默病和痴呆症的鼻内给药外泌体混合物,其特征在于:包括源自神经干细胞的外泌体、源自间充质干细胞的外泌体以及载体;鼻内给药外泌体混合物每毫升中至少含有2×109个外泌体。
2.如权利要求1所述的鼻内给药外泌体混合物,其特征在于:源自神经干细胞的外泌体和源自间充质干细胞的外泌体的体积比为1:1。
3.如权利要求1或2所述的鼻内给药外泌体混合物,其特征在于:所述鼻内给药外泌体混合物制成喷雾剂。
4.如权利要求1或2所述的鼻内给药外泌体混合物,其特征在于:所述载体为水或生理盐水。
5.如权利要求1-4任一所述的鼻内给药外泌体混合物的制备方法,其特征在于,包括以下步骤:
将神经干细胞和间充质干细胞分别培养并传代四次;
收获培养基,将培养基中的外泌体分离,分别得到源自神经干细胞的外泌体和源自间充质干细胞的外泌体;
将获得的两种外泌体混合在载体中得到鼻内给药外泌体混合物。
6.如权利要求5所述的鼻内给药外泌体混合物,其特征在于:采用超离心法将外泌体从培养基中分离。
7.如权利要求1-4任一所述的鼻内给药外泌体混合物在预防和治疗阿尔茨海默病和痴呆症中的应用。
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