CN115006423B - 四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途 - Google Patents
四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途 Download PDFInfo
- Publication number
- CN115006423B CN115006423B CN202210744656.9A CN202210744656A CN115006423B CN 115006423 B CN115006423 B CN 115006423B CN 202210744656 A CN202210744656 A CN 202210744656A CN 115006423 B CN115006423 B CN 115006423B
- Authority
- CN
- China
- Prior art keywords
- nucleic acid
- framework nucleic
- tetrahedral framework
- proliferation
- mouse
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 47
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 47
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 47
- 208000030886 Traumatic Brain injury Diseases 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims description 5
- 230000035755 proliferation Effects 0.000 claims abstract description 16
- 210000001320 hippocampus Anatomy 0.000 claims abstract description 12
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 12
- 210000001178 neural stem cell Anatomy 0.000 claims abstract description 10
- 230000009529 traumatic brain injury Effects 0.000 claims abstract description 10
- 108020004414 DNA Proteins 0.000 claims description 14
- 102000053602 DNA Human genes 0.000 claims description 5
- 108020004682 Single-Stranded DNA Proteins 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 2
- 230000000295 complement effect Effects 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 210000002165 glioblast Anatomy 0.000 claims description 2
- 239000007972 injectable composition Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 230000004663 cell proliferation Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001737 promoting effect Effects 0.000 claims 1
- 208000014674 injury Diseases 0.000 abstract description 17
- 230000008733 trauma Effects 0.000 abstract description 10
- 230000002490 cerebral effect Effects 0.000 abstract description 9
- 208000010877 cognitive disease Diseases 0.000 abstract description 8
- 230000006378 damage Effects 0.000 abstract description 8
- 208000027418 Wounds and injury Diseases 0.000 abstract description 7
- 210000001130 astrocyte Anatomy 0.000 abstract description 7
- 238000011084 recovery Methods 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 6
- 210000000274 microglia Anatomy 0.000 abstract description 4
- 230000000324 neuroprotective effect Effects 0.000 abstract description 4
- 206010018341 Gliosis Diseases 0.000 abstract description 3
- 208000036110 Neuroinflammatory disease Diseases 0.000 abstract description 3
- 230000007387 gliosis Effects 0.000 abstract description 3
- 238000010172 mouse model Methods 0.000 abstract description 3
- 230000003959 neuroinflammation Effects 0.000 abstract description 3
- 241000699670 Mus sp. Species 0.000 description 18
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 208000029028 brain injury Diseases 0.000 description 8
- 238000007619 statistical method Methods 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- LMRJHNFECNKDKH-UHFFFAOYSA-N 4-(trifluoromethyl)nicotinic acid Chemical compound OC(=O)C1=CN=CC=C1C(F)(F)F LMRJHNFECNKDKH-UHFFFAOYSA-N 0.000 description 5
- 230000002025 microglial effect Effects 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 230000000971 hippocampal effect Effects 0.000 description 3
- 210000005030 hippocampal neural stem cell Anatomy 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 238000003125 immunofluorescent labeling Methods 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 102000003952 Caspase 3 Human genes 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 238000005251 capillar electrophoresis Methods 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000012921 fluorescence analysis Methods 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 208000025978 Athletic injury Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 101000831205 Danio rerio Dynein axonemal assembly factor 11 Proteins 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 102100024282 Dynein axonemal assembly factor 11 Human genes 0.000 description 1
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 1
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 1
- 241001559542 Hippocampus hippocampus Species 0.000 description 1
- 101000831210 Homo sapiens Dynein axonemal assembly factor 11 Proteins 0.000 description 1
- 101000911513 Homo sapiens Uncharacterized protein FAM215A Proteins 0.000 description 1
- 206010061225 Limb injury Diseases 0.000 description 1
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 101150037203 Sox2 gene Proteins 0.000 description 1
- 206010041738 Sports injury Diseases 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 102100026728 Uncharacterized protein FAM215A Human genes 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000006741 behavioral dysfunction Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000005709 nerve cell growth Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明提供了四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途,属于生物医药领域。本发明首次发现,对创伤性脑损伤小鼠模型施用本发明提供的四面体框架核酸后,小鼠学习记忆能力得到改善,小鼠神经干细胞增殖促进,小鼠海马区内炎症因子的水平降低,同时小胶质细胞和星形胶质细胞的增生减少。说明本发明的四面体框架核酸能够通过减轻胶质细胞增生及炎症因子的释放,减少病灶区的神经炎症带来的继发性损伤,同时能够促进内源性神经干细胞的增殖,发挥神经保护作用,促进认知功能障碍的恢复,从多方面协同治疗脑外伤后遗症。本发明提供的四面体框架核酸能够有效治疗脑外伤后遗症,临床应用前景广阔。
Description
技术领域
本发明属于生物医药领域,具体涉及四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途。
背景技术
随着我国现代化进程的不断加快,工业、交通运输业的飞速发展以及运动损伤、意外事故和自然灾害等致伤因素的存在,脑外伤发生率日渐增高,成为我国创伤发病中仅次于四肢损伤的病种。尽管颅脑神经外科救治水平大大提高,重度脑损伤的死产率已明显降低,但脑损伤所造成的脑细胞神经元结构和功能损害仍难恢复。在我国,每年100多万罹患者中,20多万人遗留长期昏迷、瘫痪、痴呆、记忆功能减退等功能残疾。目前。脑损伤及其伴发各种功能障碍的存活者中,分别有10%、66%或100%的轻、中度和重度患者会遗留永久的残疾。其中,轻度脑损伤患者有10%-15%存在长期的认知和行为功能障碍,重度脑损伤患者至少有50%存在长期的损伤相关障碍。而记忆力、定向力、注意力、执行功能和解决问题能力等认知功能障碍往往更为突出,对患者生活的影响有时甚至远远超过躯体功能障碍,不但造成社会适应能力降低,而且给家庭和社会造成沉重负担,其治疗亦是临床重点和难点。
认知功能障碍作为脑外伤常见的后遗症之一,目前临床上尚无明确的治疗药物,主要依赖机体自身的恢复能力。对于许多患者而言,认知功能障碍可能导致其社会适应能力下降,对患者的心理造成严重的影响,甚至因此自杀。积极寻找能改善患者脑外伤后认知功能障碍的药物迫在眉睫。
目前临床上改善脑损伤后中枢神经功能的药物有:胆碱酯酶抑制剂类药如多奈哌齐,可提高严重脑损伤青少年的记忆指标;神经节苷脂类药物如单唾液酸神经节苷脂,在脑外伤常规救治的基础上,可以促进神经细胞生长,促进伤后神经功能恢复;中枢神经兴奋类药物如利他林,能促进脑损伤后认知和行为功能康复。然而这些药物大都只针对某单一环节,缺乏整体协同治疗作用;而且药物价格昂贵,治疗成本较高。亟需开发出一种价格便宜,并且能够从多方面改善脑外伤后遗症的药物。
发明内容
本发明的目的在于提供四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的新用途。
本发明提供了四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途。
进一步地,所述四面体框架核酸由4条单链DNA经碱基互补配对形成;所述4条单链DNA的序列分别为SEQ ID NO.1~4所示的序列。
进一步地,所述四面体框架核酸由如下方法制备而成:将四面体框架核酸的4条单链DNA于85~105℃下维持5min以上,然后于2~8℃下维持10min以上。
进一步地,所述四面体框架核酸由如下方法制备而成:将DNA四面体的4条单链于95℃下维持10min,然后于4℃下维持20min。
进一步地,所述脑外伤后遗症为脑外伤后认知功能障碍。
进一步地,所述脑外伤后遗症为脑外伤后神经损伤。
进一步地,所述脑外伤为创伤性脑损伤。
进一步地,所述药物是减少胶质细胞的增生,降低海马区内炎症因子的释放,促进神经干细胞的增殖,和/或改善学习记忆能力的药物。
进一步地,所述药物是以四面体框架核酸为活性成分,加上药学上可接受的辅料制备而成的制剂。
进一步地,所述制剂为注射制剂。
本发明首次发现,对创伤性脑损伤小鼠模型施用本发明提供的四面体框架核酸后,小鼠学习记忆能力得到改善,小鼠神经干细胞增殖促进,小鼠海马区内炎症因子的水平降低,同时小胶质细胞和星形胶质细胞的增生减少。说明本发明的四面体框架核酸能够通过减轻胶质细胞增生及炎症因子的释放,减少病灶区的神经炎症带来的继发性损伤,同时能够促进内源性神经干细胞的增殖,发挥神经保护作用,促进认知功能障碍的恢复,从多方面协同治疗脑外伤后遗症。
本发明提供的四面体框架核酸能够有效治疗脑外伤后遗症,临床应用前景广阔。
显然,根据本发明的上述内容,按照本领域的普通技术知识和惯用手段,在不脱离本发明上述基本技术思想前提下,还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式,对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1是四面体框架核酸及其单链的PAGE电泳图。
图2是四面体框架核酸及其单链的毛细管电泳图。
图3是四面体框架核酸的粒径图。
图4是四面体框架核酸的Zeta电位图。
图5是四面体框架核酸的透射电镜图。
图6是各组小鼠海马区神经干细胞免疫荧光染色的荧光图和统计分析图。
图7是各组小鼠海马区新生神经元细胞数量的荧光图和统计分析图。
图8是各组小鼠海马区星形胶质细胞荧光图和统计分析图。
图9是各组小鼠海马区小胶质细胞荧光图和统计分析图。
图10是各组小鼠海马区炎症因子western blot图和统计分析图。
图11是各组小鼠海马区凋亡蛋白western blot图和统计分析图。
图12是各组动物治疗后水迷宫实验结果图及统计分析图。
具体实施方式
本发明所用原料与设备均为已知产品,通过购买市售产品所得。
实施例1、四面体框架核酸的合成
将四条DNA单链(S1、S2、S3、S4)溶解于TM缓冲液(10mM Tris-HCl,50mM MgCl2,pH=8.0)中,四条DNA单链的终浓度为1μM,充分混合,迅速加热至95℃保持10分钟,之后迅速降温至4℃并维持20分钟,即可得到四面体框架核酸,简称tFNA。
表1.四条DNA单链的序列
根据四面体框架核酸的PAGE凝胶电泳(图1)和毛细管电泳(图2)可见四面体骨架核酸大小约为180KD,可认为四面体框架核酸已成功合成。四面体粒径大小约为10.8nm(图3),电位为-3.68mV(图4)。使用透射电镜观察,镜下可见特征的四面体结构(图5)。
以下通过实验例证明本发明的有益效果。
实验例1、四面体框架核酸对创伤性脑损伤模型的治疗效果
1、实验方法
模型动物:探索tFNA对创伤性脑损伤(TBI)动物的疗效,建立了TBI的标准动物模型。将小鼠随机分为三组:Control:正常对照组;TBI+saline:模型组;TBI+tFNA:模型+tFNA治疗组。
先用水合氯醛麻醉小鼠,然后将小鼠固定在立体定向仪上,沿着中线切开头皮,然后在前囟和人字缝之间,中线外1mm处,进行5×5mm的颅骨切除术。然后用3mm大小的不锈钢针头撞击大脑皮层,以4.4m/s的恒定速度产生TBI。受伤后,用精细外科缝线缝合头皮,随后将小鼠置于37°培养箱中恢复。模型+tFNA治疗组于外伤后4小时开始给予尾静脉注射0.1mL实施例1制得的四面体框架核酸(1uM),间隔24小时注射一次,连续注射15天。对照组注射等量的生理盐水,每天注射一次。
相关指标检测:急性期注射3天四面体框架核酸结束后,取小鼠脑组织切片进行免疫荧光染色,Iba-1、GFAP标记海马区小胶质细胞和星型胶质细胞的数量变化。去脑组织采用WB检测小鼠海马内炎症因子(IL-1β,IL-6,TNFα),以及小鼠脑内凋亡相关蛋白(caspase3,active caspase3)水平的变化。另外组四面体框架核酸注射15天结束后的第二天,取小鼠脑组织切片进行免疫荧光染色,分别用Brdu、Sox2、DCX标记海马区神经干细胞的增殖分化。同时,水迷宫行为学检测小鼠治疗后的认知功能情况。
2、实验结果
(1)免疫荧光发现造模组急性期小鼠海马区小胶质细胞出现明显的增多,而采用四面体框架核酸治疗后小胶质细胞明显减少,说明四面体框架核酸减少了小胶质细胞的增生(图6)。
(2)免疫荧光发现造模组急性期小鼠海马区星形胶质细胞出现明显的增多,而采用四面体框架核酸治疗后,小胶质细胞明显减少,说明四面体框架核酸减少了星形胶质细胞的增生(图7)。
(3)WB检测发现急性期治疗组小鼠海马区内炎症因子(IL-1β,IL-6,TNFα)的表达水平较模型组出现明显的下降,说明四面体框架核酸降低了脑外伤后小鼠海马区内炎症因子的水平(图8)。
(4)注射15天四面体框架核酸后采用水迷宫对小鼠进行行为学测试发现小鼠的学习记忆能力得到改善(图9)。
(5)注射15天四面体框架核酸免疫荧光发现造模组小鼠海马区神经干细胞的标记物出现明显的增多,而采用四面体框架核酸治疗后,神经干细胞标记明显增多,说明四面体框架核酸能够促进神经干细胞的增殖,发挥神经保护作用(图10)。
综上,对创伤性脑损伤小鼠模型施用本发明提供的四面体框架核酸后,小鼠学习记忆能力得到改善,小鼠神经干细胞增殖促进,小鼠海马区内炎症因子的水平降低,同时小胶质细胞和星形胶质细胞的增生减少。说明本发明的四面体框架核酸能够通过减轻胶质细胞增生及炎症因子的释放,减少病灶区的神经炎症带来的继发性损伤,同时能够促进内源性神经干细胞的增殖,发挥神经保护作用,促进认知功能障碍的恢复,从多方面协同治疗脑外伤后遗症。本发明提供的四面体框架核酸能够有效治疗脑外伤后遗症,临床应用前景广阔。
SEQUENCE LISTING
<110> 四川大学
<120> 四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途
<130> GYKH1118-2022P0115424CC
<160> 4
<170> PatentIn version 3.5
<210> 1
<211> 63
<212> DNA
<213> 人工序列
<400> 1
atttatcacc cgccatagta gacgtatcac caggcagttg agacgaacat tcctaagtct 60
gaa 63
<210> 2
<211> 63
<212> DNA
<213> 人工序列
<400> 2
acatgcgagg gtccaatacc gacgattaca gcttgctaca cgattcagac ttaggaatgt 60
tcg 63
<210> 3
<211> 63
<212> DNA
<213> 人工序列
<400> 3
actactatgg cgggtgataa aacgtgtagc aagctgtaat cgacgggaag agcatgccca 60
tcc 63
<210> 4
<211> 63
<212> DNA
<213> 人工序列
<400> 4
acggtattgg accctcgcat gactcaactg cctggtgata cgaggatggg catgctcttc 60
ccg 63
Claims (3)
1.四面体框架核酸在制备预防和/或治疗创伤性脑损伤后遗症的药物中的用途;
所述四面体框架核酸由4条单链DNA经碱基互补配对形成;所述4条单链DNA的序列分别为SEQ ID NO.1~4所示的序列;
所述四面体框架核酸由如下方法制备而成:将DNA四面体的4条单链于95℃下维持10min,然后于4℃下维持20min;
所述药物是减少胶质细胞的增生,降低海马区内炎症因子的释放,促进神经干细胞的增殖和改善学习记忆能力的药物。
2.如权利要求1所述的用途,其特征在于,所述药物是以四面体框架核酸为活性成分,加上药学上可接受的辅料制备而成的制剂。
3.如权利要求1或2所述的用途,其特征在于,所述制剂为注射制剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210744656.9A CN115006423B (zh) | 2022-06-28 | 2022-06-28 | 四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210744656.9A CN115006423B (zh) | 2022-06-28 | 2022-06-28 | 四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115006423A CN115006423A (zh) | 2022-09-06 |
CN115006423B true CN115006423B (zh) | 2023-07-18 |
Family
ID=83077127
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210744656.9A Active CN115006423B (zh) | 2022-06-28 | 2022-06-28 | 四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115006423B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115919816B (zh) * | 2022-09-27 | 2024-04-09 | 四川大学 | 姜黄素-四面体框架核酸载药系统在制备预防或治疗放射性口腔黏膜炎的药物中的用途 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003095967A2 (en) * | 2002-05-14 | 2003-11-20 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with chemokine receptor 9(ccr9) |
CN101420991A (zh) * | 2003-11-20 | 2009-04-29 | 血管技术国际股份公司 | 聚合物组合物及其使用方法 |
CN111494401A (zh) * | 2019-08-22 | 2020-08-07 | 四川大学 | Dna四面体在制备促进成肌细胞增殖的药物中的用途 |
CN112641796A (zh) * | 2020-12-28 | 2021-04-13 | 四川大学 | 一种缺血性脑卒中的神经保护药物 |
CN112843085A (zh) * | 2021-03-18 | 2021-05-28 | 四川大学 | 一种治疗视神经疾病的复合物及其制备方法和用途 |
CN113274400A (zh) * | 2021-06-07 | 2021-08-20 | 四川大学 | 四面体框架核酸在治疗多发性硬化症的药物中的用途 |
CN114159458A (zh) * | 2021-12-10 | 2022-03-11 | 四川大学 | 四面体框架核酸在治疗癫痫的药物中的用途 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7288563B2 (en) * | 2004-02-19 | 2007-10-30 | Bristol-Myers Squibb Company | Substituted bicycloalkylamine derivatives as modulators of chemokine receptor activity |
-
2022
- 2022-06-28 CN CN202210744656.9A patent/CN115006423B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003095967A2 (en) * | 2002-05-14 | 2003-11-20 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with chemokine receptor 9(ccr9) |
CN101420991A (zh) * | 2003-11-20 | 2009-04-29 | 血管技术国际股份公司 | 聚合物组合物及其使用方法 |
CN111494401A (zh) * | 2019-08-22 | 2020-08-07 | 四川大学 | Dna四面体在制备促进成肌细胞增殖的药物中的用途 |
CN112641796A (zh) * | 2020-12-28 | 2021-04-13 | 四川大学 | 一种缺血性脑卒中的神经保护药物 |
CN112843085A (zh) * | 2021-03-18 | 2021-05-28 | 四川大学 | 一种治疗视神经疾病的复合物及其制备方法和用途 |
CN113274400A (zh) * | 2021-06-07 | 2021-08-20 | 四川大学 | 四面体框架核酸在治疗多发性硬化症的药物中的用途 |
CN114159458A (zh) * | 2021-12-10 | 2022-03-11 | 四川大学 | 四面体框架核酸在治疗癫痫的药物中的用途 |
Non-Patent Citations (4)
Title |
---|
"Tetrahedral framework nucleic acids promote cognitive impairment recovery post traumatic brain injury";Yangyang Wang,et al;《Chinese Chemical Letters》;第34卷;第1-7页。 * |
"四面体框架核酸材料与人类健康";林云锋;《四川大学学报》;第第52卷卷(第第3期期);第343-348页。 * |
"Design, fabrication and applications of tetrahedral DNA nanostructure-based multifunctional complexes in drug delivery and biomedical treatment";Tao Zhang,et al;《Nature Protocols》;第15卷;第2728-2755页 * |
"Therapeutic siCCR2 Loaded by Tetrahedral Framework DNA Nanorobotics in Therapy for Intracranial Hemorrhag";Wei Fu, Lu Ma,et al;《Advanced functional materials》;第31卷;第1-12页 * |
Also Published As
Publication number | Publication date |
---|---|
CN115006423A (zh) | 2022-09-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Caracciolo et al. | CREB controls cortical circuit plasticity and functional recovery after stroke | |
Schäbitz et al. | Intraventricular brain-derived neurotrophic factor reduces infarct size after focal cerebral ischemia in rats | |
Frank | Sleep and developmental plasticity: not just for kids | |
CN112843085B (zh) | 一种治疗视神经疾病的复合物及其制备方法和用途 | |
Ivanco et al. | Physiological consequences of morphologically detectable synaptic plasticity: potential uses for examining recovery following damage | |
CN113274400B (zh) | 四面体框架核酸在治疗多发性硬化症的药物中的用途 | |
CN115006423B (zh) | 四面体框架核酸在制备预防和/或治疗脑外伤后遗症的药物中的用途 | |
Li et al. | miR‐22‐3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis | |
CN114159458A (zh) | 四面体框架核酸在治疗癫痫的药物中的用途 | |
CN113134011B (zh) | miR-129在制备治疗抑郁症产品中的应用 | |
Lin et al. | The conditioned medium of lactobacillus rhamnoides gg regulates microglia/macrophage polarization and improves functional recovery after spinal cord injury in rats | |
Yasoshima et al. | Subthalamic neurons coordinate basal ganglia function through differential neural pathways | |
Liu et al. | The therapeutic mechanism of transcranial iTBS on nerve regeneration and functional recovery in rats with complete spinal cord transection | |
Liu et al. | Basic fibroblast growth factor-induced seizures in rats | |
Attar et al. | Electron microscopic study of the progeny of ependymal stem cells in the normal and injured spinal cord | |
Quan et al. | Hydralazine plays an immunomodulation role of pro-regeneration in a mouse model of spinal cord injury | |
Yan et al. | Repair effects of bone marrow mesenchymal stem cells on demyelination of trigeminal ganglion in rats with trigeminal neuralgia | |
Gulia et al. | Assessment of the septal area neuronal activity during penile erections in rapid eye movement sleep and waking in the rats | |
CN1053360A (zh) | 与系统免疫功能障碍有关的神经认知症的诊断和治疗 | |
CN106619693A (zh) | 长非编码核糖核酸uc.48+小干扰RNA在三叉神经痛治疗药物中的应用 | |
Casanova et al. | Responsiveness of reorganized primary somatosensory (SI) cortex after local inactivation of normal SI cortex in chronic spinal cats | |
CN109223817B (zh) | 一种微小非编码rna的拮抗剂及其应用 | |
Xerri et al. | Neuroprotective effects on somatotopic maps resulting from piracetam treatment and environmental enrichment after focal cortical injury | |
SAKODA et al. | Responses of Pineocytoma to Radiation Therapy and Chemotherapy—Report of Two Cases— | |
CN116376910B (zh) | 一种三叉神经痛的标志物及治疗三叉神经的药物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20240711 Address after: Room 1-17, 15th Floor, Building 2, No. 89, North Section 4, Second Ring Road, Jinniu District, Chengdu City, Sichuan Province, 610000 Patentee after: Chengdu Yunhai Tetrahedral Biotechnology Co.,Ltd. Country or region after: China Address before: 610000 No. 24 south part of Wuhou District first ring road, Chengdu, Sichuan. Patentee before: SICHUAN University Country or region before: China |