CN114917350B - Cftr增强剂在注意缺陷与多动障碍中的应用及产品 - Google Patents
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Abstract
本发明公开了CFTR增强剂在注意缺陷与多动障碍中的应用及产品,属于生物工程技术领域。CFTR增强剂单独或联合使用,能够很好地恢复行为学异常表型,因此,为注意缺陷与多动障碍的新治疗药物等提供可靠的理论依据。
Description
技术领域
本发明涉及CFTR增强剂在注意缺陷与多动障碍中的应用及产品,属于生物工程技术领域。
背景技术
注意缺陷与多动障碍 (Attention deficit and hyperactivity disorder,ADHD)俗称多动症,指发生于儿童时期,与同龄儿童相比,以明显注意集中困难、注意持续时间短暂、活动过度或冲动为主要特征的一组综合征。多动症是在儿童中较为常见的一种障碍,其患病率约为3-5%,男女比例为4:1。
目前,已发现很多方法具有减轻症状的作用,比如现有技术:CN104523932A中公开一种治疗小儿多动症的中药组合物、及其制备方法和应用,CN102416012A中公开一种治疗小儿多动症的药物组合物,CN104474341A中公开一种治疗小儿多动症的药物组合物等,但至今无法治愈ADHD,为此,需要提出更多的治疗用药物,为临床使用提供更多的参考。
发明内容
在长期的研究中,发明人团队发现:CFTR 增强剂单独或联合使用,能够很好地恢复行为学异常表型(如:活动过度、认知障碍和学习困难等异常状态),且具有统计学意义,基于此,将CFTR 增强剂应用于制备注意缺陷与多动障碍治疗的产品中,为新的治疗方案提供可靠的理论依据。
为了实现上述技术目的,提出如下的技术方案:
本技术方案提出:CFTR 增强剂在注意缺陷与多动障碍中的应用,包括所述CFTR增强剂在制备注意缺陷与多动障碍治疗的产品中的应用。
进一步的,所述CFTR 增强剂包括Ivacaftor或/和VX-809。优选的,CFTR 增强剂包括Ivacaftor和VX-809。
进一步的,所述CFTR 增强剂中,Ivacaftor终浓度为10 µm,VX-809终浓度为10 µm。
本技术方案还提出:CFTR 增强剂或其药学上可用的盐为活性成分,以及药学上可接受的载体、稀释剂和赋形剂组成的药物组合物的产品。
进一步的,所述产品为用于治疗注意缺陷与多动障碍的药物组合物。
进一步的,所述CFTR 增强剂包括Ivacaftor或/和VX-809。优选的,CFTR 增强剂包括Ivacaftor和VX-809。
进一步的,所述CFTR 增强剂中,Ivacaftor终浓度为10 µm,VX-809终浓度为10 µm。
在本技术方案中,涉及的术语包括:
CFTR,囊性纤维化跨膜调节因子(cystic fibrosis transmembrane conductanceregulator);
Ivacaftor (VX-770)为一种CFTR的选择性增强剂,靶向作用于G551D-CFTR和F508del-CFTR,提高G551D、 F508del和野生型CFTR 的离子通道开放概率;
VX-809 (Lumacaftor) 通过促进突变型CFTR(F508del-CFTR)的成熟,从而纠正囊性纤维症中常见的CFTR突变,提高CFTR成熟度,且增强CFTR的氯离子运输能力。
采用本技术方案,带来的有益技术效果为:
一、本发明首次将CFTR 增强剂单独或联合使用,应用于制备注意缺陷与多动障碍治疗的产品中。该CFTR 增强剂可显著的恢复行为学异常表型,为注意缺陷与多动障碍的新治疗方案提供可靠的理论依据;
其中,较发明人前期研究“CN109663129A扩张型心肌病治疗药物及其应用”而言,本发明为CFTR 增强剂的一种全新用途;
二、本发明通过建立ADHD斑马鱼模型,证据充分,具有很强的理论支撑,能够很好地表现注意缺陷与多动障碍的症状和治疗效果。其中,涉及的实验手段为本领域的成熟技术,易操作,表现性强。且选用了特定的CFTR 增强剂,对注意缺陷与多动障碍的治疗具有明显效果,便于进行推广使用;
三、将CFTR 增强剂Ivacaftor与VX-809一并应用于制备注意缺陷与多动障碍治疗的产品中时,即联合使用,具有更好的效果。
附图说明
图1为CFTR激动剂可显著降低ADHD斑马鱼模型的幼鱼的游动距离的结果图;
图2为CFTR激动剂可显著降低ADHD斑马鱼模型的幼鱼的游动速度的结果图;
图3为CFTR激动剂可显著降低ADHD斑马鱼模型的成鱼的镜面攻击次数的结果图;
图4为CFTR激动剂可显著减少ADHD斑马鱼模型的成鱼提高其学习能力的学习时间的结果图。
具体实施方式
以下通过具体实施方式的描述对本发明作进一步说明,但这并非是对本发明的限制,本领域技术人员根据本发明的基本思想,可以做出各种修改或改进,但是只要不脱离本发明的基本思想,均在本发明的范围之内。
在如下实施例中,涉及的ADHD斑马鱼模型,来自苏州大学,通过per1b基因突变而构建,详见“Circadian Modulation of Dopamine Levels and Dopaminergic NeuronDevelopment Contributes to Attention Deficiency and Hyperactive Behavior,DOI:10.1523/JNEUROSCI.2551-14.2015”。
实施例1
本实施例提出:CFTR 增强剂在注意缺陷与多动障碍中的应用,包括CFTR 增强剂在制备注意缺陷与多动障碍治疗的产品中的应用。其中,CFTR 增强剂包括Ivacaftor或/和VX-809。
作为优选,CFTR 增强剂包括Ivacaftor和VX-809,Ivacaftor终浓度为10 µm,VX-809终浓度为10 µm。
实施例2
本实施例提出:CFTR 增强剂或其药学上可用的盐为活性成分,以及药学上可接受的载体、稀释剂和赋形剂组成的药物组合物的产品。其中,产品为用于治疗注意缺陷与多动障碍的药物组合物。CFTR 增强剂包括Ivacaftor或/和VX-809。
作为优选,CFTR 增强剂包括Ivacaftor和VX-809,Ivacaftor终浓度为10 µm,VX-809终浓度为10 µm。
实施例3
基于实施例1-2,本实施例提出:基于ADHD斑马鱼模型,讨论将CFTR 增强剂(Ivacaftor与VX-809联合使用)用于ADHD斑马鱼模型的幼鱼,具体如下:
1、向ADHD斑马鱼模型的受精卵的胚胎培养基中,加入Ivacaftor和VX-809 (VX-770和VX-809皆来源于Selleck公司,目录号分别为S1144和S1565),设为实验组。其中,Ivacaftor和VX-809终浓度均为10 µm,连续处理培养5天;
2、以野生型斑马鱼、ADHD斑马鱼模型分别为对照组,相同条件下进行胚胎培养。其中,均不加入Ivacaftor和VX-809,连续处理培养5天;
3、在培养第6天,检测实验组、两个对照组对应幼鱼的游动距离和游动速度;
结果表明:联合使用Ivacaftor和VX-809,可显著降低ADHD斑马鱼模型的幼鱼的游动距离和游动速度(如图1-2所示)。
实施例4
基于实施例1-2,本实施例提出:基于ADHD斑马鱼模型,讨论将CFTR 增强剂(Ivacaftor与VX-809联合使用)用于ADHD斑马鱼模型的成鱼,具体如下:
1、向ADHD斑马鱼模型的成鱼(6个月)腹腔联合注射Ivacaftor和VX-809(VX-770和VX-809皆来源于Selleck公司,目录号分别为S1144和S1565),设为实验组。其中,注射方法参考atg7-Based Autophagy Activation Reverses Doxorubicin-InducedCardiotoxicity,DOI: 10.1161/CIRCRESAHA.121.319104,Ivacaftor及VX-809的注射量皆为2mg/kg;
2、以野生型斑马鱼、ADHD斑马鱼模型分别为对照组。其中,均不注射Ivacaftor和VX-809;
3、实验组注射1天后,检测成鱼的学习能力;同时,检测两个对照组对应成鱼的学习能力;
结果表明:联合注射Ivacaftor和VX-809,可显著降低ADHD斑马鱼模型的成鱼的镜面攻击次数,并减少其学习的时间提高其学习能力(如图3-4所示)。
Claims (2)
1.CFTR 增强剂在制备注意缺陷与多动障碍治疗的产品中的应用,其特征在于:所述CFTR 增强剂为Ivacaftor和VX-809。
2.根据权利要求1所述的CFTR 增强剂在制备注意缺陷与多动障碍治疗的产品中的应用,其特征在于:所述CFTR 增强剂中,Ivacaftor终浓度为10 µm,VX-809终浓度为10 µm。
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