[go: up one dir, main page]

CN117679522A - Pharmaceutical compositions for preventing and treating neurological lesions and their applications - Google Patents

Pharmaceutical compositions for preventing and treating neurological lesions and their applications Download PDF

Info

Publication number
CN117679522A
CN117679522A CN202311159266.6A CN202311159266A CN117679522A CN 117679522 A CN117679522 A CN 117679522A CN 202311159266 A CN202311159266 A CN 202311159266A CN 117679522 A CN117679522 A CN 117679522A
Authority
CN
China
Prior art keywords
pharmaceutical composition
injection
present
nerve
preferred technical
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.)
Pending
Application number
CN202311159266.6A
Other languages
Chinese (zh)
Inventor
陈琳
王宇
高文勇
李建军
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beijing Darwin Cell Biotechnology Co Ltd
Original Assignee
Beijing Darwin Cell Biotechnology Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Beijing Darwin Cell Biotechnology Co Ltd filed Critical Beijing Darwin Cell Biotechnology Co Ltd
Publication of CN117679522A publication Critical patent/CN117679522A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H39/00—Devices for locating or stimulating specific reflex points of the body for physical therapy, e.g. acupuncture
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
    • 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
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • 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
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/185—Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A63—SPORTS; GAMES; AMUSEMENTS
    • A63B—APPARATUS FOR PHYSICAL TRAINING, GYMNASTICS, SWIMMING, CLIMBING, OR FENCING; BALL GAMES; TRAINING EQUIPMENT
    • A63B23/00—Exercising apparatus specially adapted for particular parts of the body
    • A63B23/025—Exercising apparatus specially adapted for particular parts of the body for the head or the neck
    • A63B23/03—Exercising apparatus specially adapted for particular parts of the body for the head or the neck for face muscles

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Molecular Biology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Neurosurgery (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Rehabilitation Therapy (AREA)
  • Botany (AREA)
  • Otolaryngology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Cell Biology (AREA)

Abstract

The invention relates to application of a pharmaceutical composition in preparing medicines for preventing and treating nervous system diseases, wherein the pharmaceutical composition for preventing and treating nervous system diseases contains a nerve repairing medicine and/or a blood circulation improving medicine and an anti-inflammatory medicine. The invention scientifically screens the components and the proportion of the pharmaceutical composition, adopts any one or the combination of cerebrospinal fluid injection (including intrathecal injection, intraventricular injection and the like), acupoint injection and intravenous injection, and leads the medicine to directly enter subarachnoid space or cerebral chamber of brain and spinal cord, reach the parenchyma of brain and spinal cord and nerve injury part through cerebrospinal fluid circulation, directly supply nerve repair medicine or nerve nutrient substance to neurons and glial cells, eliminate medicine absorption disorder caused by blood brain barrier, obviously improve the medicine peak concentration in central nervous system tissue and effectively treat nerve function deficiency or nerve dysfunction.

Description

用于防治神经系统病变的药物组合物及其应用Pharmaceutical composition for preventing and treating nervous system diseases and its application

技术领域Technical Field

本发明属于生物医药技术领域，具体涉及一种用于防治神经系统病变的药物组合物及其应用。The present invention belongs to the technical field of biomedicine, and specifically relates to a pharmaceutical composition for preventing and treating nervous system diseases and an application thereof.

背景技术Background Art

脑血管病(cerebrovascular disease)泛指脑部血管的各种疾病，包括脑动脉粥样硬化、血栓形成、狭窄、闭塞、脑动脉炎、脑动脉损伤、脑动脉瘤、颅内血管畸形、脑动静脉瘘等，所引起的脑组织的缺血或出血性意外，导致患者的致残或死亡，发病率占神经系统总住院病例的1/4-1/2。Cerebrovascular disease refers to various diseases of the brain's blood vessels, including cerebral atherosclerosis, thrombosis, stenosis, occlusion, cerebral arteritis, cerebral artery injury, cerebral aneurysm, intracranial vascular malformation, cerebral arteriovenous fistula, etc., which cause ischemic or hemorrhagic accidents of the brain tissue, leading to disability or death of the patient. The incidence rate accounts for 1/4-1/2 of the total hospitalizations for the nervous system.

脑卒中(cerebral stroke)是一种急性脑血管疾病，由于脑部血管突然破裂或因血管阻塞导致血液不能流入大脑而引起脑组织损伤的一组疾病，包括缺血性和出血性卒中，我国成年人致死致残的首要原因。Cerebral stroke is an acute cerebrovascular disease, a group of diseases caused by sudden rupture of cerebral blood vessels or blockage of blood vessels that prevent blood from flowing into the brain, resulting in brain tissue damage. It includes ischemic and hemorrhagic stroke and is the leading cause of death and disability among adults in my country.

临床使用的脑卒中治疗药物主要包括:溶栓药物、抗血小板聚集药物、降纤药物、抗凝药物和神经保护药物等。溶栓药物包括阿替普酶、尿激酶等，对发病早期患者有一定的疗效，但也有出血风险，用药需要经过医生的评估，符合适应症且排除禁忌症才可使用，且剂量、有效时间窗等研究仍然不成熟，有待于进一步探索研究；抗血小板聚集药物包括阿司匹林，氢氯吡格雷，双嘧达莫等，部分服用阿司匹林、氯吡格雷等的患者再发血管事件几率仍很高；降纤药物与抗凝药物治疗主要是用于急性超早期的治疗措施，主要用于溶解血栓和预防血栓的再发生；神经保护药物用于干预半暗带的瀑布级联效应，但存在安全隐患。Clinically used drugs for the treatment of stroke mainly include: thrombolytic drugs, antiplatelet aggregation drugs, defibrinolytic drugs, anticoagulant drugs and neuroprotective drugs. Thrombolytic drugs include alteplase, urokinase, etc., which have certain efficacy for patients in the early stage of the disease, but also have the risk of bleeding. The use of drugs needs to be evaluated by doctors, and can only be used when it meets the indications and excludes contraindications. The research on dosage, effective time window, etc. is still immature and needs further exploration and research; antiplatelet aggregation drugs include aspirin, clopidogrel, dipyridamole, etc., and some patients taking aspirin, clopidogrel, etc. still have a high probability of recurrent vascular events; defibrinolytic drugs and anticoagulant drugs are mainly used for acute and ultra-early treatment measures, mainly for dissolving thrombi and preventing the recurrence of thrombi; neuroprotective drugs are used to intervene in the waterfall cascade effect of the penumbra, but there are safety risks.

因脑或脊髓神经损伤、神经系统损伤、颅脑损伤、神经退行性病变、卒中、心脑血管疾病等疾病，所导致的神经系统功能缺失或神经功能障碍患者逐年增多，由此导致全球神经系统疾病的发病率逐年攀升，且严重影响人类健康，增加社会负担，但又缺少有效的治疗药物。The number of patients with neurological dysfunction or neurological dysfunction caused by brain or spinal cord injury, nervous system injury, craniocerebral injury, neurodegenerative diseases, stroke, cardiovascular and cerebrovascular diseases and other diseases increases year by year. As a result, the incidence of neurological diseases in the world is rising year by year, seriously affecting human health and increasing the social burden, but there is a lack of effective treatment drugs.

多种药物在体外呈现神经细胞和周围神经细胞具有细胞修复、营养支持等效果。但其通过常规给药途径(肌肉注射、静脉注射、口服给药、粘膜给药等)给药，无法通过血脑屏障(blood barrier)而限制其发挥神经修复、营养支持等作用。为此，需要研究开发更为安全有效的神经修复功效的药物组合物，以满足临床需求。Many drugs have shown in vitro effects on nerve cells and peripheral nerve cells such as cell repair and nutritional support. However, they are administered through conventional routes of administration (intramuscular injection, intravenous injection, oral administration, mucosal administration, etc.), and cannot pass through the blood-brain barrier, which limits their role in nerve repair and nutritional support. Therefore, it is necessary to study and develop safer and more effective drug compositions with nerve repair effects to meet clinical needs.

专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)公开了有关具有修复功效的神经修复蛋白提取物及神经修复蛋白组合物的技术内容，前述申请及内容作为本申请必不可少的技术参考和组成部分。Patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582) disclose technical contents related to nerve repair protein extracts and nerve repair protein compositions with repair effects. The aforementioned applications and contents serve as indispensable technical references and components of this application.

发明内容Summary of the invention

本发明的目的在于提供一种药物组合物用于制备防治神经系统病变的药物中的应用，其中，所述用于防治神经系统病变的药物组合物含有神经修复药物和/改善血液循环药物和消炎药物。The object of the present invention is to provide a pharmaceutical composition for use in preparing a drug for preventing and treating nervous system diseases, wherein the pharmaceutical composition for preventing and treating nervous system diseases contains a nerve repair drug and/or a blood circulation improving drug and an anti-inflammatory drug.

本发明的优选技术方案中，所述的神经修复药物和/改善血液循环药物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。In the preferred technical scheme of the present invention, the nerve repair drug and/or blood circulation improving drug is selected from any one or a combination of mouse nerve growth factor, monosialoganglioside (GM1), cerebroside carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline sodium, ganglioside, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and neuraminic acid.

本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from any one of dexamethasone, methylprednisolone, prednisone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, and prednisolone, or a combination thereof.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物由单次脑脊液鞘内注射用的药物组合物和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system diseases consists of a pharmaceutical composition for single intrathecal injection of cerebrospinal fluid and a pharmaceutical composition for single acupoint injection.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子15ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺或维生素B12或胞磷胆碱的任一种0.25mg-1.0mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松2mg-5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 15ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.25mg-1.0mg of adenosylcobalamin or vitamin B12 or citicoline, 2ml-8ml of any one of cerebroside carnosine or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg-5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺或维生素B12或胞磷胆碱的任一种0.25mg-1.0mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种4ml-6ml或神经节苷脂20-40mg和地塞米松2mg-5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 30ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.25mg-1.0mg of any one of adenosylcobalamin or vitamin B12 or citicoline, 4ml-6ml of any one of cerebroside carnosine or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg-5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种4ml-6ml或神经节苷脂20-40mg和地塞米松2mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml-6ml of any one of cerebroside myosin or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射用的药物组合物由鼠神经生长因子60ug、甲钴胺1.0mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松3mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid is composed of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside myosin or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 3mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽4ml和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml of cerebroside carnosine and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg和地塞米松2-5mg组成。In the preferred technical solution of the present invention, the pharmaceutical composition for single intrathecal injection of cerebrospinal fluid consists of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin and 2-5 mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合，优选为150-200mg。In a preferred technical solution of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid optionally contains 100-300 mg of any one or a combination of a neural repair cell protein extract and/or a neural repair protein composition having a repair effect, preferably 150-200 mg.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物任选地含有2-10mg盐酸纳洛酮，优选为5-8mg。In a preferred technical solution of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid optionally contains 2-10 mg naloxone hydrochloride, preferably 5-8 mg.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺0.5mg-1.0mg、地塞米松2mg-5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.5mg-1.0mg of adenosylcobalamin, 2mg-5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺1.0mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子60ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of a nerve repair cell protein extract and/or a nerve repair protein composition having a repair effect.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is prepared and used immediately.

本发明的优选技术方案中，选取患侧肢体的合谷穴、手三里、手五里、足三里、阳陵泉、阴陵泉、三阴交和阳交穴并选取健侧的合谷穴和足三里穴进行穴位注射。In the preferred technical solution of the present invention, Hegu, Shousanli, Shouwuli, Zusanli, Yanglingquan, Yinlingquan, Sanyinjiao and Yangjiao points of the affected limb are selected, and Hegu and Zusanli points of the healthy side are selected for acupoint injection.

本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected into the acupoint once a day, and the treatment course is 7 days.

本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.

本发明的优选技术方案中，所述的脑脊液鞘内注射选自腰椎穿刺、植入性鞘内药物输注系统，经Ommaya囊穿刺注射的任一种或其组合。In the preferred technical solution of the present invention, the intrathecal injection of cerebrospinal fluid is selected from any one of lumbar puncture, implantable intrathecal drug infusion system, and injection via Ommaya capsule puncture or a combination thereof.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物任选地含有单次静脉注射用的药物组合物。In a preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system diseases optionally contains a pharmaceutical composition for single intravenous injection.

本发明的优选技术方案中，单次静脉注射用的药物组合物具有与单次脑脊液鞘内注射用的药物组合物相同的组分及配比。In the preferred technical solution of the present invention, the pharmaceutical composition for single intravenous injection has the same components and proportions as the pharmaceutical composition for single intrathecal injection of cerebrospinal fluid.

本发明的优选技术方案中，单次脑脊液鞘内注射用的药物组合物、单次静脉注射用的药物组合物与单次穴位注射药物序贯用药或同时用药。In the preferred technical solution of the present invention, the pharmaceutical composition for single cerebrospinal fluid intrathecal injection, the pharmaceutical composition for single intravenous injection and the drug for single acupoint injection are administered sequentially or simultaneously.

本发明的优选技术方案中，每周脑脊液鞘内注射或静脉注射2次，两周为一个疗程，治疗四周。In the preferred technical solution of the present invention, the cerebrospinal fluid is injected intrathecally or intravenously twice a week, two weeks is a course of treatment, and the treatment is four weeks.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物任选地与物理疗法、康复训练的任一种或其组合联用。In a preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system diseases is optionally used in combination with any one of physical therapy and rehabilitation training or a combination thereof.

本发明的优选技术方案中，所述的物理疗法选自电刺激、外治与推拿、膏摩疗法、外敷疗法、针灸、皮肤针法、电针法、刺络拔罐法、低频电疗法、星状神经节阻滞疗法、耳穴疗法、高压氧疗法、微创穴位埋线的任一种或其组合。In the preferred technical scheme of the present invention, the physical therapy is selected from any one or a combination of electrical stimulation, external treatment and massage, ointment massage, external application therapy, acupuncture, skin acupuncture, electroacupuncture, pricking and cupping, low-frequency electrotherapy, stellate ganglion block therapy, auricular acupuncture, hyperbaric oxygen therapy, and minimally invasive acupuncture thread embedding.

本发明的优选技术方案中，所述的康复训练选自徒手功能训练改善肌肉及筋膜的弹性及张力使瘫痪的肌肉本体感受器受到刺激加快功能重建、根据瘫痪程度进行被动运动、筋膜松解的任一种或其组合。In the preferred technical solution of the present invention, the rehabilitation training is selected from any one or a combination of manual functional training to improve the elasticity and tension of muscles and fascia so that the paralyzed muscle proprioceptors are stimulated to accelerate functional reconstruction, passive exercise according to the degree of paralysis, and fascia release.

本发明的优选技术方案中，所述神经系统病变选自脑卒中、脑外伤及后遗症、脊髓损伤及后遗症、脑血管病及后遗症、运动神经元病、脑性瘫痪、帕金森病、痴呆、脊髓炎后遗症、脑膜炎后遗症、脑炎后遗症、脑发育不良、脑萎缩、共济失调、多发性硬化、视神经脊髓炎、多系统萎缩、持续植物生存状态、一氧化碳中毒迟发性脑病、颅神经损害性疾病、脑肿瘤及术后神经功能障碍、椎管内肿瘤及术后神经功能障碍、神经病理性疼痛、颈胸腰椎病变继发的神经损害、癫痫继发的脑损害中的任一种或其组合。In the preferred technical scheme of the present invention, the nervous system lesions are selected from any one or a combination of cerebral stroke, brain trauma and sequelae, spinal cord injury and sequelae, cerebrovascular disease and sequelae, motor neuron disease, cerebral palsy, Parkinson's disease, dementia, sequelae of myelitis, sequelae of meningitis, sequelae of encephalitis, brain dysplasia, cerebral atrophy, ataxia, multiple sclerosis, neuromyelitis optica, multiple system atrophy, persistent vegetative state, delayed encephalopathy due to carbon monoxide poisoning, cranial nerve damage diseases, brain tumors and postoperative neurological dysfunction, intraspinal tumors and postoperative neurological dysfunction, neuropathic pain, nerve damage secondary to cervical, thoracic and lumbar spine lesions, and brain damage secondary to epilepsy.

本发明的目的在于提供一种用于防治神经系统病变的药物组合物，所述用于防治神经系统病变的药物组合物含有神经修复药物和/改善血液循环药物和消炎药物。The object of the present invention is to provide a pharmaceutical composition for preventing and treating nervous system diseases, wherein the pharmaceutical composition for preventing and treating nervous system diseases contains a nerve repair drug and/or a blood circulation improving drug and an anti-inflammatory drug.

本发明的优选技术方案中，所述的神经修复药物和/改善血液循环药物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。In the preferred technical scheme of the present invention, the nerve repair drug and/or blood circulation improving drug is selected from any one or a combination of mouse nerve growth factor, monosialoganglioside (GM1), cerebroside carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline sodium, ganglioside, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and neuraminic acid.

本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from any one of dexamethasone, methylprednisolone, prednisone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, and prednisolone, or a combination thereof.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物由单次脑脊液鞘内注射用的药物组合物和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system diseases consists of a pharmaceutical composition for single intrathecal injection of cerebrospinal fluid and a pharmaceutical composition for single acupoint injection.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子15ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺或维生素B12或胞磷胆碱的任一种0.25mg-1.0mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松2mg-5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 15ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.25mg-1.0mg of adenosylcobalamin or vitamin B12 or citicoline, 2ml-8ml of any one of cerebroside carnosine or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg-5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺或维生素B12或胞磷胆碱的任一种0.25mg-1.0mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种4ml-6ml或神经节苷脂20-40mg和地塞米松2mg-5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 30ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.25mg-1.0mg of any one of adenosylcobalamin or vitamin B12 or citicoline, 4ml-6ml of any one of cerebroside carnosine or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg-5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种4ml-6ml或神经节苷脂20-40mg和地塞米松2mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml-6ml of any one of cerebroside or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射用的药物组合物由鼠神经生长因子60ug、甲钴胺1.0mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松3mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid is composed of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside myosin or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 3mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽4ml和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml of cerebroside carnosine and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg和地塞米松2-5mg组成。In the preferred technical solution of the present invention, the pharmaceutical composition for single intrathecal injection of cerebrospinal fluid consists of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin and 2-5 mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合，优选为150-200mg。In a preferred technical solution of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid optionally contains 100-300 mg of any one or a combination of a neural repair cell protein extract and/or a neural repair protein composition having a repair effect, preferably 150-200 mg.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物任选地含有2-10mg盐酸纳洛酮，优选为5-8mg。In a preferred technical solution of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid optionally contains 2-10 mg naloxone hydrochloride, preferably 5-8 mg.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺0.5mg-1.0mg、地塞米松2mg-5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.5mg-1.0mg of adenosylcobalamin, 2mg-5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺1.0mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子60ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of a nerve repair cell protein extract and/or a nerve repair protein composition having a repair effect.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is prepared and used immediately.

本发明的优选技术方案中，选取患侧肢体的合谷穴、手三里、手五里、足三里、阳陵泉、阴陵泉、三阴交和阳交穴并选取健侧的合谷穴和足三里穴进行穴位注射。In the preferred technical solution of the present invention, Hegu, Shousanli, Shouwuli, Zusanli, Yanglingquan, Yinlingquan, Sanyinjiao and Yangjiao points of the affected limb are selected, and Hegu and Zusanli points of the healthy side are selected for acupoint injection.

本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected into the acupoint once a day, and the treatment course is 7 days.

本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.

本发明的优选技术方案中，所述的脑脊液鞘内注射选自腰椎穿刺、植入性鞘内药物输注系统，经Ommaya囊穿刺注射的任一种或其组合。In the preferred technical solution of the present invention, the intrathecal injection of cerebrospinal fluid is selected from any one of lumbar puncture, implantable intrathecal drug infusion system, and injection via Ommaya capsule puncture or a combination thereof.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物任选地含有单次静脉注射用的药物组合物。In a preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system diseases optionally contains a pharmaceutical composition for single intravenous injection.

本发明的优选技术方案中，单次静脉注射用的药物组合物具有与单次脑脊液鞘内注射用的药物组合物相同的组分及配比。In the preferred technical solution of the present invention, the pharmaceutical composition for single intravenous injection has the same components and proportions as the pharmaceutical composition for single intrathecal injection of cerebrospinal fluid.

本发明的优选技术方案中，单次脑脊液鞘内注射用的药物组合物、单次静脉注射用的药物组合物与单次穴位注射药物序贯用药或同时用药。In the preferred technical solution of the present invention, the pharmaceutical composition for single cerebrospinal fluid intrathecal injection, the pharmaceutical composition for single intravenous injection and the drug for single acupoint injection are administered sequentially or simultaneously.

本发明的优选技术方案中，每周脑脊液鞘内注射或静脉注射2次，两周为一个疗程，治疗四周。In the preferred technical solution of the present invention, the cerebrospinal fluid is injected intrathecally or intravenously twice a week, two weeks is a course of treatment, and the treatment is four weeks.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物任选地与物理疗法、康复训练的任一种或其组合联用。In a preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system diseases is optionally used in combination with any one of physical therapy and rehabilitation training or a combination thereof.

本发明的优选技术方案中，所述的物理疗法选自电刺激、外治与推拿、膏摩疗法、外敷疗法、针灸、皮肤针法、电针法、刺络拔罐法、低频电疗法、星状神经节阻滞疗法、耳穴疗法、高压氧疗法、微创穴位埋线的任一种或其组合。In the preferred technical scheme of the present invention, the physical therapy is selected from any one or a combination of electrical stimulation, external treatment and massage, ointment massage, external application therapy, acupuncture, skin acupuncture, electroacupuncture, pricking and cupping, low-frequency electrotherapy, stellate ganglion block therapy, auricular acupuncture, hyperbaric oxygen therapy, and minimally invasive acupuncture thread embedding.

本发明的优选技术方案中，所述的康复训练选自徒手功能训练改善肌肉及筋膜的弹性及张力使瘫痪的肌肉本体感受器受到刺激加快功能重建、根据瘫痪程度进行被动运动、筋膜松解的任一种或其组合。In the preferred technical solution of the present invention, the rehabilitation training is selected from any one or a combination of manual functional training to improve the elasticity and tension of muscles and fascia so that the paralyzed muscle proprioceptors are stimulated to accelerate functional reconstruction, passive exercise according to the degree of paralysis, and fascia release.

本发明的优选技术方案中，所述神经系统病变选自脑卒中、脑外伤及后遗症、脊髓损伤及后遗症、脑血管病及后遗症、运动神经元病、脑性瘫痪、帕金森病、痴呆、脊髓炎后遗症、脑膜炎后遗症、脑炎后遗症、脑发育不良、脑萎缩、共济失调、多发性硬化、视神经脊髓炎、多系统萎缩、持续植物生存状态、一氧化碳中毒迟发性脑病、颅神经损害性疾病、脑肿瘤及术后神经功能障碍、椎管内肿瘤及术后神经功能障碍、神经病理性疼痛、颈胸腰椎病变继发的神经损害、癫痫继发的脑损害中的任一种或其组合。In the preferred technical scheme of the present invention, the nervous system lesions are selected from any one or a combination of cerebral stroke, brain trauma and sequelae, spinal cord injury and sequelae, cerebrovascular disease and sequelae, motor neuron disease, cerebral palsy, Parkinson's disease, dementia, sequelae of myelitis, sequelae of meningitis, sequelae of encephalitis, brain dysplasia, cerebral atrophy, ataxia, multiple sclerosis, neuromyelitis optica, multiple system atrophy, persistent vegetative state, delayed encephalopathy due to carbon monoxide poisoning, cranial nerve damage diseases, brain tumors and postoperative neurological dysfunction, intraspinal tumors and postoperative neurological dysfunction, neuropathic pain, nerve damage secondary to cervical, thoracic and lumbar spine lesions, and brain damage secondary to epilepsy.

本发明的另一目的在于提供一种防治神经系统病变的治疗方案，所述治疗方案包括用于防治神经系统病变的药物组合物含有神经修复药物和/改善血液循环药物和消炎药物。Another object of the present invention is to provide a treatment plan for preventing and treating nervous system diseases, wherein the treatment plan includes a pharmaceutical composition for preventing and treating nervous system diseases containing a nerve repair drug and/or a blood circulation improving drug and an anti-inflammatory drug.

本发明的优选技术方案中，所述的神经修复药物和/改善血液循环药物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。In the preferred technical scheme of the present invention, the nerve repair drug and/or blood circulation improving drug is selected from any one or a combination of mouse nerve growth factor, monosialoganglioside (GM1), cerebroside carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline sodium, ganglioside, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and neuraminic acid.

本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from any one of dexamethasone, methylprednisolone, prednisone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, and prednisolone, or a combination thereof.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物由单次脑脊液鞘内注射用的药物组合物和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system diseases consists of a pharmaceutical composition for single cerebrospinal fluid intrathecal injection and a pharmaceutical composition for single acupoint injection.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子15ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺或维生素B12或胞磷胆碱的任一种0.25mg-1.0mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松2mg-5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 15ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.25mg-1.0mg of adenosylcobalamin or vitamin B12 or citicoline, 2ml-8ml of any one of cerebroside carnosine or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg-5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺或维生素B12或胞磷胆碱的任一种0.25mg-1.0mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种4ml-6ml或神经节苷脂20-40mg和地塞米松2mg-5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 30ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.25mg-1.0mg of any one of adenosylcobalamin or vitamin B12 or citicoline, 4ml-6ml of any one of cerebroside carnosine or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg-5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside glycosyltransferase or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种4ml-6ml或神经节苷脂20-40mg和地塞米松2mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml-6ml of any one of cerebroside myosin or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 2mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射用的药物组合物由鼠神经生长因子60ug、甲钴胺1.0mg、腺苷钴胺0.5mg、脑苷肌肽或单唾液酸神经节苷脂(GM1)或复方脑肽节苷脂的任一种2ml-8ml或神经节苷脂20-40mg和地塞米松3mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid is composed of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2ml-8ml of any one of cerebroside myosin or monosialoganglioside (GM1) or compound cerebroside ganglioside or 20-40mg of ganglioside and 3mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽4ml和地塞米松5mg组成。In the preferred technical scheme of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml of cerebroside carnosine and 5mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物由甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg和地塞米松2-5mg组成。In the preferred technical solution of the present invention, the pharmaceutical composition for single intrathecal injection of cerebrospinal fluid consists of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin and 2-5 mg of dexamethasone.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合，优选为150-200mg。In a preferred technical solution of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid optionally contains 100-300 mg of any one or a combination of a neural repair cell protein extract and/or a neural repair protein composition having a repair effect, preferably 150-200 mg.

本发明的优选技术方案中，单次脑脊液鞘内注射的药物组合物任选地含有2-10mg盐酸纳洛酮，优选为5-8mg。In a preferred technical solution of the present invention, the pharmaceutical composition for a single intrathecal injection of cerebrospinal fluid optionally contains 2-10 mg naloxone hydrochloride, preferably 5-8 mg.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺0.5mg-1.0mg、地塞米松2mg-5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug-90ug of mouse nerve growth factor, 0.5mg-1.0mg of methylcobalamin, 0.5mg-1.0mg of adenosylcobalamin, 2mg-5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺1.0mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子60ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of a nerve repair cell protein extract and/or a nerve repair protein composition having a repair effect.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is prepared and used immediately.

本发明的优选技术方案中，选取患侧肢体的合谷穴、手三里、手五里、足三里、阳陵泉、阴陵泉、三阴交和阳交穴并选取健侧的合谷穴和足三里穴进行穴位注射。In the preferred technical solution of the present invention, Hegu, Shousanli, Shouwuli, Zusanli, Yanglingquan, Yinlingquan, Sanyinjiao and Yangjiao points of the affected limb are selected, and Hegu and Zusanli points of the healthy side are selected for acupoint injection.

本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected into the acupoint once a day, and the treatment course is 7 days.

本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.

本发明的优选技术方案中，所述的脑脊液鞘内注射选自腰椎穿刺、植入性鞘内药物输注系统，经Ommaya囊穿刺注射的任一种或其组合。In the preferred technical solution of the present invention, the intrathecal injection of cerebrospinal fluid is selected from any one of lumbar puncture, implantable intrathecal drug infusion system, and injection via Ommaya capsule puncture or a combination thereof.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物任选地含有单次静脉注射用的药物组合物。In a preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system diseases optionally contains a pharmaceutical composition for single intravenous injection.

本发明的优选技术方案中，单次静脉注射用的药物组合物具有与单次脑脊液鞘内注射用的药物组合物相同的组分及配比。In the preferred technical solution of the present invention, the pharmaceutical composition for single intravenous injection has the same components and proportions as the pharmaceutical composition for single intrathecal injection of cerebrospinal fluid.

本发明的优选技术方案中，单次脑脊液鞘内注射用的药物组合物、单次静脉注射用的药物组合物与单次穴位注射药物序贯用药或同时用药。In the preferred technical solution of the present invention, the pharmaceutical composition for single cerebrospinal fluid intrathecal injection, the pharmaceutical composition for single intravenous injection and the drug for single acupoint injection are administered sequentially or simultaneously.

本发明的优选技术方案中，每周脑脊液鞘内注射或静脉注射2次，两周为一个疗程，治疗四周。In the preferred technical solution of the present invention, the cerebrospinal fluid is injected intrathecally or intravenously twice a week, two weeks is a course of treatment, and the treatment is four weeks.

本发明的优选技术方案中，所述用于防治神经系统病变的药物组合物任选地与物理疗法、康复训练的任一种或其组合联用。In a preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating nervous system lesions is optionally used in combination with any one of physical therapy and rehabilitation training or a combination thereof.

本发明的优选技术方案中，所述的物理疗法选自电刺激、外治与推拿、膏摩疗法、外敷疗法、针灸、皮肤针法、电针法、刺络拔罐法、低频电疗法、星状神经节阻滞疗法、耳穴疗法、高压氧疗法、微创穴位埋线的任一种或其组合。In the preferred technical scheme of the present invention, the physical therapy is selected from any one or a combination of electrical stimulation, external treatment and massage, ointment massage, external application therapy, acupuncture, skin acupuncture, electroacupuncture, pricking and cupping, low-frequency electrotherapy, stellate ganglion block therapy, auricular therapy, hyperbaric oxygen therapy, and minimally invasive acupuncture thread embedding.

本发明的优选技术方案中，所述的康复训练选自徒手功能训练改善肌肉及筋膜的弹性及张力使瘫痪的肌肉本体感受器受到刺激加快功能重建、根据瘫痪程度进行被动运动、筋膜松解的任一种或其组合。In the preferred technical scheme of the present invention, the rehabilitation training is selected from any one or a combination of manual functional training to improve the elasticity and tension of muscles and fascia so that the paralyzed muscle proprioceptors are stimulated to accelerate functional reconstruction, passive exercise according to the degree of paralysis, and fascia release.

本发明的优选技术方案中，所述神经系统病变选自脑卒中、脑外伤及后遗症、脊髓损伤及后遗症、脑血管病及后遗症、运动神经元病、脑性瘫痪、帕金森病、痴呆、脊髓炎后遗症、脑膜炎后遗症、脑炎后遗症、脑发育不良、脑萎缩、共济失调、多发性硬化、视神经脊髓炎、多系统萎缩、持续植物生存状态、一氧化碳中毒迟发性脑病、颅神经损害性疾病、脑肿瘤及术后神经功能障碍、椎管内肿瘤及术后神经功能障碍、神经病理性疼痛、颈胸腰椎病变继发的神经损害、癫痫继发的脑损害中的任一种或其组合。In the preferred technical scheme of the present invention, the nervous system lesions are selected from any one or a combination of cerebral stroke, brain trauma and sequelae, spinal cord injury and sequelae, cerebrovascular disease and sequelae, motor neuron disease, cerebral palsy, Parkinson's disease, dementia, sequelae of myelitis, sequelae of meningitis, sequelae of encephalitis, brain dysplasia, cerebral atrophy, ataxia, multiple sclerosis, neuromyelitis optica, multiple system atrophy, persistent vegetative state, delayed encephalopathy due to carbon monoxide poisoning, cranial nerve damage diseases, brain tumors and postoperative neurological dysfunction, intraspinal tumors and postoperative neurological dysfunction, neuropathic pain, nerve damage secondary to cervical, thoracic and lumbar spine lesions, and brain damage secondary to epilepsy.

为了清楚地表述本发明，本发明所述的具有修复功效的神经修复细胞蛋白提取物或神经修复细胞蛋白组合物参照专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)制得。In order to clearly describe the present invention, the nerve repair cell protein extract or nerve repair cell protein composition with repair efficacy described in the present invention is prepared with reference to patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582).

本发明的优选技术方案中，所述具有神经修复功效的神经修复细胞蛋白提取物的制备方法，包括如下步骤：In the preferred technical solution of the present invention, the method for preparing the nerve repair cell protein extract having nerve repair efficacy comprises the following steps:

S-1:将密度为5.0×106个/mL-5.0×107个/mL的间充质传代干细胞置于含有DMEM/F12 40-50％、RPMI1640 40-50％、牛血清蛋白(BSA)0.1-2％、表皮细胞生长因子(EGF)1-15ug/mL、成纤维细胞生长因子(FGF)1-15ug/mL、胰岛素转铁蛋白1-15ug/mL、复方氨基酸(18AA)0.01-0.1％和2-10μmol/L应激物的培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养2h-6h后，分离，洗涤，收集细胞，其中，所述的应激物选自化合物1-16的任一种或其组合；S-1: placing mesenchymal stem cells with a density of 5.0×10 6 cells/mL-5.0× 10 7 cells/mL in a culture medium containing DMEM/F12 40-50%, RPMI1640 40-50%, bovine serum albumin (BSA) 0.1-2%, epidermal growth factor (EGF) 1-15ug/mL, fibroblast growth factor (FGF) 1-15ug/mL, insulin transferrin 1-15ug/mL, compound amino acid (18AA) 0.01-0.1% and 2-10μmol/L stressor, and then culturing them at 37.0℃±0.5℃, 5%±1.0% CO 2 for 2h-6h, separating, washing and collecting the cells, wherein the stressor is selected from any one or a combination of compounds 1-16;

S-2：将收集细胞按照密度为5.0×106个/mL-5.0×107个/mL分散于溶剂中，再将其置于2℃-8℃条件下超声处理，制得细胞裂解液，其中，所述溶剂选自选自生理盐水、5％葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合；S-2: Dispersing the collected cells in a solvent at a density of 5.0×10 6 cells/mL-5.0 ×10 7 cells/mL, and then subjecting the cells to ultrasonic treatment at 2°C-8°C to obtain a cell lysate, wherein the solvent is selected from any one of physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, and Tris buffer, or a combination thereof;

S-3:将步骤S-2制得的细胞裂解液分离后，所得的分离液依次经0.45um、0.22um滤膜过滤，即得。S-3: After the cell lysate obtained in step S-2 is separated, the obtained separation solution is filtered through 0.45um and 0.22um filter membranes in sequence.

本发明的优选技术方案中，步骤S-1的培养基中含有DMEM/F12 42-45％、RPMI164042-45％、牛血清蛋白(BSA)0.5-1.5％、表皮细胞生长因子(EGF)5-10ug/mL、成纤维细胞生长因子(FGF)5-10ug/mL、胰岛素转铁蛋白5-10ug/mL、复方氨基酸(18AA)0.02-0.05％和3-8μmol/L的应激物。In the preferred technical scheme of the present invention, the culture medium of step S-1 contains DMEM/F12 42-45%, RPMI164042-45%, bovine serum albumin (BSA) 0.5-1.5%, epidermal growth factor (EGF) 5-10ug/mL, fibroblast growth factor (FGF) 5-10ug/mL, insulin transferrin 5-10ug/mL, compound amino acid (18AA) 0.02-0.05% and 3-8μmol/L of stressor.

本发明的优选技术方案中，步骤S-1的培养基中含有DMEM/F12 45％、RPMI164045％、牛血清蛋白(BSA)0.5％、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL，胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05％和4-6μmol/L的应激物。In the preferred technical scheme of the present invention, the culture medium of step S-1 contains DMEM/F12 45%, RPMI164045%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10ug/mL, fibroblast growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 4-6μmol/L of stressor.

本发明的优选技术方案中，步骤S-1的间充质传代干细胞密度为8.0×106-2.0×107个/mL，优选为8.0×106-1.0×107个/mL。In a preferred technical solution of the present invention, the density of the mesenchymal stem cells in step S-1 is 8.0×10 6 -2.0×10 7 cells/mL, preferably 8.0×10 6 -1.0×10 7 cells/mL.

本发明的优选技术方案中，步骤S-1的间充质传代干细胞在培养基中培养3h-5h，优选为3.5h-4.5h。In a preferred technical solution of the present invention, the mesenchymal stem cells in step S-1 are cultured in the culture medium for 3h-5h, preferably 3.5h-4.5h.

本发明的优选技术方案中，步骤S-1中洗涤细胞的溶剂选自生理盐水、5％葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合,细胞洗涤次数为2-5次，优选为3-4次。In a preferred technical solution of the present invention, the solvent for washing cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, Tris buffer or a combination thereof, and the number of cell washing times is 2-5 times, preferably 3-4 times.

本发明的优选技术方案中，步骤S-1所述的分离选自离心、过滤的任一种或其组合，其中，所述离心条件为1000-2000rpm*3-15min，优选为1200rpm-1500rpm*5-10min。In the preferred technical scheme of the present invention, the separation described in step S-1 is selected from any one of centrifugation and filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm*3-15min, preferably 1200rpm-1500rpm*5-10min.

本发明的优选技术方案中，步骤S-2的超声条件为：在2℃-8℃、25kHZ、360W条件下工作3s再间隙1s，超声处理1-5min。In the preferred technical solution of the present invention, the ultrasonic conditions of step S-2 are: working for 3s and then resting for 1s at 2°C-8°C, 25kHZ, 360W, and ultrasonic treatment for 1-5min.

本发明的优选技术方案中，步骤S-3所述分离选自2000-8000rpm*10-30min离心、多级离心、多级过滤的任一种或其组合，优选为3000-7000rpm*15-25min。In the preferred technical solution of the present invention, the separation in step S-3 is selected from any one of 2000-8000rpm*10-30min centrifugation, multi-stage centrifugation, multi-stage filtration or a combination thereof, preferably 3000-7000rpm*15-25min.

本发明的优选技术方案中，步骤S-3的多级离心依次为3000-4000rpm*3-5min、5000-6000rpm*3-5min和7000rpm*5-8min。In the preferred technical solution of the present invention, the multi-stage centrifugation in step S-3 is 3000-4000rpm*3-5min, 5000-6000rpm*3-5min and 7000rpm*5-8min respectively.

本发明的优选技术方案中，所述多级过滤的滤膜孔径选自80um、50um、30um、10um、5um的任一种。In the preferred technical solution of the present invention, the pore size of the filter membrane for multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.

本发明的优选技术方案中，将步骤S-3制得的细胞蛋白提取物冻存，优选冻存于-40℃至-20℃。In a preferred technical solution of the present invention, the cell protein extract obtained in step S-3 is frozen, preferably at -40°C to -20°C.

本发明的优选技术方案中，将步骤S-3制得的细胞蛋白提取物采用核酸酶或全能核酸酶的任一种酶解后再分离纯化。In a preferred technical solution of the present invention, the cell protein extract obtained in step S-3 is hydrolyzed by either nuclease or omnipotent nuclease and then separated and purified.

本发明的优选技术方案中，所述间充质传代干细胞的培养或原代间充质干细胞的培养采用本领域的培养方法。In a preferred technical solution of the present invention, the culture of the mesenchymal stem cells or the culture of the primary mesenchymal stem cells adopts a culture method in the art.

本发明的优选技术方案中，所述间充质传代干细胞的培养包括下述步骤：将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到传代培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养10-15天，每隔2-3天，观察传代培养基变黄后，半量更换传代培养基，其中，所述传代培养基含有10％FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基。In the preferred technical scheme of the present invention, the culture of the mesenchymal stem cells comprises the following steps: adding primary mesenchymal stem cells to a subculture medium at an initial density of 5.0×10 5 -5.0×10 6 cells/ml, and then culturing them at 37.0°C±0.5°C and 5%±1.0% CO 2 for 10-15 days, and replacing half of the subculture medium after observing that the subculture medium turns yellow every 2-3 days, wherein the subculture medium contains a DMEM/F12 medium containing 10% FBS, 100U/ml penicillin and 100ug/ml streptomycin.

本发明的优选技术方案中，所述原代间充质干细胞的培养包括下述步骤：In the preferred technical solution of the present invention, the culturing of primary mesenchymal stem cells comprises the following steps:

1)将脐带清洗消毒后，组织解剖，取华通胶层组织，将其切成3mm3的小块，离心，清洗，收集组织块，将其置于含10％胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养，每间隔2-3天半量更换培养基，培养至组织块爬出细胞；1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Wharton's jelly tissue, cut it into small pieces of 3 mm3, centrifuge, wash, collect the tissue blocks, place them in DMEM/F12 culture medium containing 10% fetal bovine serum FBS, 100ug/ml penicillin, and 100ug/ml streptomycin, and then culture them at 37.0℃±0.5℃, 5%±1.0% CO2 . Replace half of the culture medium every 2-3 days until the tissue blocks crawl out of the cells;

2)振摇，收集低层细胞用PBS清洗后，加入0.25％的胰蛋白酶消化2min-3min，加入等体积的胰蛋白酶终止液停止消化，吸管轻轻吹打，1200-1500rpm/min*5-8min离心后，收集细胞，即得。2) Shake and collect the lower layer cells, wash with PBS, add 0.25% trypsin to digest for 2min-3min, add an equal volume of trypsin stop solution to stop digestion, pipette gently to blow, centrifuge at 1200-1500rpm/min*5-8min, and collect the cells.

为了清楚地表述本发明，本发明所述的神经修复蛋白组合物的制备方法，包括如下步骤：In order to clearly describe the present invention, the preparation method of the nerve repair protein composition of the present invention comprises the following steps:

(1)在本发明的神经修复细胞蛋白提取物中加入20U/mL-35U/mL的核酸酶或全能核酸酶的任一种或其组合，将其置于37℃±1℃条件下酶解15min-40min，制得酶解液；(1) adding 20U/mL-35U/mL of any one or combination of nuclease or universal nuclease to the neural repair cell protein extract of the present invention, placing it at 37°C±1°C for enzymatic hydrolysis for 15min-40min to obtain an enzymatic hydrolyzate;

(2)在2℃-8℃条件下，将步骤(1)制得的酶解液用洗脱溶剂配置成5-15mg/ml后，过色谱柱，洗脱流速为0.1-1ml/min，监测并收集紫外波长为280nm的洗脱馏分，即得，其中，洗脱溶剂由50mmol/L磷酸盐缓冲液(pH6.8)中含300mmol/L氯化钠组成。(2) at 2°C-8°C, the enzymatic hydrolysate obtained in step (1) is prepared with an elution solvent to a concentration of 5-15 mg/ml, and then passed through a chromatographic column at an elution flow rate of 0.1-1 ml/min, and the elution fraction with an ultraviolet wavelength of 280 nm is monitored and collected, wherein the elution solvent is composed of 300 mmol/L sodium chloride in 50 mmol/L phosphate buffer (pH 6.8).

本发明的优选技术方案中，所述核酸酶选自RNA核酸酶、DNA核酸酶的任一种或其组合。In a preferred technical solution of the present invention, the nuclease is selected from any one of RNA nuclease and DNA nuclease or a combination thereof.

本发明的优选技术方案中，在本发明的细胞蛋白提取物中加入25U/mL-30U/mL的核酸酶或全能核酸酶的任一种或其组合，将其置于37℃±1℃条件下酶解20min-30min，制得酶解液。In a preferred technical solution of the present invention, 25U/mL-30U/mL of any one or a combination of nuclease or universal nuclease is added to the cell protein extract of the present invention, and the extract is placed at 37°C±1°C for enzymatic hydrolysis for 20min-30min to obtain an enzymatic hydrolyzate.

本发明的优选技术方案中，所述神经修复蛋白组合物的分子量为20kDa-250kDa，优选为35kDa-200kDa。In a preferred technical solution of the present invention, the molecular weight of the nerve repair protein composition is 20 kDa-250 kDa, preferably 35 kDa-200 kDa.

本发明的优选技术方案中，将步骤(2)所得蛋白组合物冻存，优选冻存于-40℃至-20℃。In a preferred technical solution of the present invention, the protein composition obtained in step (2) is frozen, preferably at -40°C to -20°C.

本发明的优选技术方案中，在步骤(2)收集的蛋白组合物中加入冻干保护剂，冻干，制得蛋白组合物冻干制剂，其中，所述冻干保护剂选自甘露醇、山梨糖醇、右旋糖酐、甘油、蔗糖、海藻糖、葡萄糖、乳糖、麦芽糖、葡聚糖、三辛酸甘油酯(HES)、聚乙二醇、乙烯乙二烯、磷酸盐、醋酸盐、柠檬酸盐、山梨醇、淀粉中的任一种或其组合。In a preferred technical scheme of the present invention, a lyophilization protective agent is added to the protein composition collected in step (2), and lyophilized to obtain a lyophilized preparation of the protein composition, wherein the lyophilization protective agent is selected from any one of mannitol, sorbitol, dextran, glycerol, sucrose, trehalose, glucose, lactose, maltose, dextran, tricaprylin (HES), polyethylene glycol, ethylene glycol, phosphate, acetate, citrate, sorbitol, starch, or a combination thereof.

本发明的优选技术方案中，以质量百分比计，所述冻干制剂中含有冻干保护剂0.5-8％，优选为1-5％。In a preferred technical solution of the present invention, the freeze-dried preparation contains 0.5-8%, preferably 1-5%, of freeze-protectant by mass percentage.

本发明的优选技术方案中，将步骤(2)收集的蛋白组合物中任选地加入蛋白稳定剂，其中，所述蛋白稳定剂选自白蛋白、锌盐、铝盐的任一种。In a preferred technical solution of the present invention, a protein stabilizer is optionally added to the protein composition collected in step (2), wherein the protein stabilizer is selected from any one of albumin, zinc salt, and aluminum salt.

本发明的优选技术方案，所述冻干制剂pH6-8，优选为pH7-7.5。According to a preferred technical solution of the present invention, the lyophilized preparation has a pH of 6-8, preferably a pH of 7-7.5.

本发明的优选技术方案中，所述冻干制剂临用前用生理盐水或5％葡萄糖溶液复溶后，采用静脉注射、鞘内注射、腰椎穿刺的任一种或其组合方式使用。In a preferred technical solution of the present invention, the lyophilized preparation is reconstituted with physiological saline or 5% glucose solution before use, and then used by intravenous injection, intrathecal injection, lumbar puncture or any one or a combination thereof.

除非另有说明，本发明涉及液体与液体之间的百分比时，所述的百分比为体积/体积百分比；本发明涉及液体与固体之间的百分比时，所述百分比为体积/重量百分比；本发明涉及固体与液体之间的百分比时，所述百分比为重量/体积百分比；其余为重量/重量百分比。Unless otherwise specified, when the present invention relates to the percentage between liquids, the percentage is volume/volume percentage; when the present invention relates to the percentage between liquids and solids, the percentage is volume/weight percentage; when the present invention relates to the percentage between solids and liquids, the percentage is weight/volume percentage; the rest are weight/weight percentages.

除非另有说明，本发明使用表1脑卒中评分量表和表2的Barthel指数(ModifiedBarthel Index，MBI)作为评分量表。Unless otherwise specified, the present invention uses the stroke scoring scale in Table 1 and the Barthel Index (Modified Barthel Index, MBI) in Table 2 as the scoring scale.

表1脑卒中评分量表Table 1 Stroke Rating Scale

说明:在相应项目内打“√”，每项检查只能选填一项。Note: Please tick “√” in the corresponding item. Only one item can be selected for each inspection.

最高分45分，最低分0分。The highest score is 45 points and the lowest score is 0 points.

轻型:0-15分，中型:16-30分，重型:31-45分。Mild: 0-15 points, moderate: 16-30 points, severe: 31-45 points.

表2日常生活活动(ADL)量表(Barthel指数)Table 2 Activities of daily living (ADL) scale (Barthel index)

评分结果：Rating results:

满分100分Full score: 100

<20分为极严重功能缺陷，生活完全需要依赖；20—40分为生活需要很大帮助；40—60分为生活需要帮助；>60分为生活基本自理。<20 points indicate extremely severe functional impairment and complete dependence in life; 20-40 points indicate a need for great help in life; 40-60 points indicate a need for help in life; >60 points indicate basic self-care.

Barthel指数得分40分以上者康复治疗的效益最大。Those with a Barthel index score of 40 or above have the greatest benefit from rehabilitation treatment.

ADL能力缺陷程度：0—20为严重功能缺陷；20—45＝严重功能缺陷；50—70＝中度功能缺陷；75—95＝轻度功能缺陷；100＝ADL自理Degree of ADL impairment: 0-20 = severe impairment; 20-45 = severe impairment; 50-70 = moderate impairment; 75-95 = mild impairment; 100 = ADL self-care

与现有技术相比，本发明具有下述有益效果：Compared with the prior art, the present invention has the following beneficial effects:

本发明科学筛选药物组合物的组分及配比，并采用脑脊液注射给药(包括鞘内注射给药、脑室内给药等)、穴位注射给药、静脉注射给药的任一种或其组合，脑脊液注射给药使得药物直接进入脑与脊髓的蛛网膜下腔或脑室内，通过脑脊液循环而到达脑与脊髓实质内及神经损伤部位，直接向神经元和神经胶质细胞供应神经修复药物或神经营养物质，消除血脑屏障导致的药物吸收障碍，显著提高中枢神经系统组织中药物峰浓度，有效治疗神经功能缺失或神经功能障碍，所述药物组合物具有协同增效、起效快、给药量少、生物利用度高、基本无副作用和基本无复发率等优点，显著改善患者的治疗预后和生活质量。The present invention scientifically screens the components and proportions of the pharmaceutical composition, and adopts any one or a combination of cerebrospinal fluid injection (including intrathecal injection, intraventricular administration, etc.), acupoint injection, and intravenous injection. Cerebrospinal fluid injection allows the drug to directly enter the subarachnoid space or intraventricular space of the brain and spinal cord, reach the brain and spinal cord substance and the nerve injury site through the cerebrospinal fluid circulation, directly supply nerve repair drugs or neurotrophic substances to neurons and glial cells, eliminate drug absorption disorders caused by the blood-brain barrier, significantly increase the peak concentration of drugs in central nervous system tissues, and effectively treat neurological deficits or neurological dysfunctions. The pharmaceutical composition has the advantages of synergistic enhancement, rapid onset, small dosage, high bioavailability, basically no side effects and basically no recurrence rate, and significantly improves the patient's treatment prognosis and quality of life.

具体实施方式DETAILED DESCRIPTION

下面结合具体实施例对本发明的详细内容做进一步解释和描述，但并不以此限制本发明的保护范围。The details of the present invention are further explained and described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto.

实施例1具有修复功效的神经修复细胞蛋白提取物的制备 Example 1 Preparation of nerve repair cell protein extract with repair efficacy

1、原代间充质干细胞的培养1. Culture of primary mesenchymal stem cells

原代间充质干细胞的培养包括下述步骤：The culture of primary mesenchymal stem cells includes the following steps:

1)将脐带清洗消毒后，组织解剖，取华通胶层组织，将其切成3mm3的小块，离心，清洗，收集组织块，将其置于培养瓶中，加入含10％胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基，再将其置于37℃、5％CO2条件下培养，促进其贴壁，每间隔2-3天,观察培养基变黄后，半量更换培养基，培养10-12天，至组织块边上可见细胞爬出；1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Wharton's jelly tissue, cut it into small pieces of 3 mm3, centrifuge, wash, collect the tissue pieces, place them in a culture bottle, add DMEM/F12 culture medium containing 10% fetal bovine serum FBS, 100ug/ml penicillin, and 100ug/ml streptomycin, and then culture them at 37℃ and 5% CO2 to promote their adhesion . After observing the culture medium turn yellow every 2-3 days, replace half of the culture medium and culture for 10-12 days until cells can be seen crawling out of the edge of the tissue block;

2)轻轻摇晃，使组织块掉落，分别收集组织块和低层细胞，其中，将收集的组织块再贴壁培养；2) Gently shake the tissue blocks to make them fall off, collect the tissue blocks and the lower layer cells respectively, and culture the collected tissue blocks again on the wall;

3)将收集的低层细胞用PBS清洗后，加入适量0.25％胰蛋白酶消化2min-3min，加入等体积的胰蛋白酶终止液停止消化，吸管轻轻吹打瓶底，1500rpm*5min离心后，收集细胞，即得。3) After washing the collected lower layer cells with PBS, add an appropriate amount of 0.25% trypsin to digest for 2min-3min, add an equal volume of trypsin stop solution to stop digestion, gently blow the bottom of the bottle with a pipette, centrifuge at 1500rpm*5min, and collect the cells.

2、原代间充质干细胞的传代培养(间充质传代干细胞的培养)2. Subculture of primary mesenchymal stem cells (Cultivation of mesenchymal stem cells)

原代间充质干细胞的传代培养(间充质传代干细胞的培养)：将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到含有10％FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养10-15天，每间隔2-3天，观察培养基变黄后，半量更换培养基。Subculture of primary mesenchymal stem cells (culture of mesenchymal subcultured stem cells): Add primary mesenchymal stem cells to DMEM/F12 culture medium containing 10% FBS, 100U/ml penicillin and 100ug/ml streptomycin at an initial density of 5.0×10 5 -5.0×10 6 cells/ml, and then culture them at 37.0℃±0.5℃, 5%±1.0% CO 2 for 10-15 days. Replace half of the culture medium every 2-3 days when the culture medium turns yellow.

3、化合物1-16的制备参照文献1(New limonophyllines A-C from the stem ofAtalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2cell lines，Arch.Pharm.Res.(2018)41:431–437)。3. The preparation of compounds 1-16 refers to document 1 (New limonophyllines A-C from the stem of Atalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2 cell lines, Arch. Pharm. Res. (2018) 41: 431-437).

具有神经修复功效的神经修复细胞蛋白提取物的制备方法，包括如下步骤：A method for preparing a nerve repair cell protein extract having a nerve repair effect comprises the following steps:

(1)将间充质传代细胞按照密度为8.0×106个/mL加入到含有DMEM/F1245％、RPMI1640 45％、牛血清蛋白(BSA)0.5％、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL、胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05％和5μmol/L的化合物16的培养基中，再将其置于37℃、5％CO2条件下培养4h后，将其置于1200rpm*5min离心，用PBS洗涤3次后，收集细胞；(1) The mesenchymal passage cells were added to a culture medium containing 45% DMEM/F12, 45% RPMI1640, 0.5% bovine serum albumin (BSA), 10ug/mL epidermal growth factor (EGF), 10ug /mL fibroblast growth factor (FGF), 10ug/mL insulin transferrin, 0.05% compound amino acid (18AA) and 5μmol/L compound 16 at a density of 8.0×10 6 cells/mL, and then cultured at 37°C and 5% CO 2 for 4 hours, and then centrifuged at 1200 rpm*5 min, washed 3 times with PBS, and then the cells were collected;

(2)将步骤(1)收集的细胞按照密度为1.0×107个/mL分散于生理盐水中，在2-8℃、25kHz、360W条件下超声3s、间隙1s，超声2min，制得细胞裂解液；(2) dispersing the cells collected in step (1) at a density of 1.0×10 7 cells/mL in physiological saline, and sonicating for 3 seconds, with a 1 second interval, and for 2 minutes at 2-8° C., 25 kHz, and 360 W to obtain a cell lysate;

(3)将步骤(2)制得的细胞裂解液置于7000rpm*20min离心，将所得的离心液依次经0.45um、0.22um滤膜过滤，即得细胞蛋白提取物。(3) The cell lysate obtained in step (2) was centrifuged at 7000 rpm for 20 min, and the obtained centrifuge was filtered through 0.45 um and 0.22 um filter membranes in turn to obtain a cell protein extract.

实施例2神经修复蛋白组合物的制备 Example 2 Preparation of nerve repair protein composition

本发明神经修复蛋白组合物的制备包括如下步骤：The preparation of the nerve repair protein composition of the present invention comprises the following steps:

(1)在实施例1制得的细胞蛋白提取物中，加入25U/mL的全能核酸酶(UCF.MEUltraNuclease)，将其置于37℃酶解30min后，制得酶解液；(1) Add 25 U/mL of UCF.ME UltraNuclease to the cell protein extract prepared in Example 1, and place it at 37° C. for 30 min to obtain an enzymatic solution;

(2)在2℃-8℃条件下，将步骤(1)制得的酶解液用洗脱溶剂配置成10mg/ml，依次过高纯硅胶液相色谱保护柱(WondaGuard C18，4.6×5mm)、高纯硅胶液相色谱制备柱(SHIMSEN Ankylo C18，5μm，4.6×250mm)，洗脱流速为0.1-1ml/min，监测并收集紫外波长为280nm的洗脱馏分，即得，其中，洗脱溶剂由50mmol/L磷酸盐缓冲液(pH6.8)中含300mmol/L氯化钠组成。(2) at 2°C-8°C, the enzymatic hydrolyzate obtained in step (1) is prepared with an elution solvent to a concentration of 10 mg/ml, and sequentially passed through a high-purity silica gel liquid chromatography guard column (WondaGuard C18, 4.6×5 mm) and a high-purity silica gel liquid chromatography preparative column (SHIMSEN Ankylo C18, 5 μm, 4.6×250 mm) at an elution flow rate of 0.1-1 ml/min, and the elution fraction with an ultraviolet wavelength of 280 nm is monitored and collected to obtain the product, wherein the elution solvent is composed of 300 mmol/L sodium chloride in 50 mmol/L phosphate buffer (pH 6.8).

(3)在步骤(2)制得的细胞蛋白组合物中加入甘露醇，搅拌，混合均匀后，冻干，所得冻干制剂中含有2.15％的甘露醇(m/m)。(3) Adding mannitol to the cell protein composition obtained in step (2), stirring, mixing evenly, and then freeze-drying. The resulting freeze-dried preparation contains 2.15% mannitol (m/m).

试验例1本发明药物组合物用于缺血性脑卒中的治疗效果研究 Experimental Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention on ischemic stroke

(一)受试者(I) Subjects

选取缺血性脑卒中患者30名，分为1组(5名)、2组(20名)和3组(5名)。各组受试者在年龄、疾病类型、性别等方面，统计学无显著差异(P＞0.05)。Thirty patients with ischemic stroke were selected and divided into group 1 (5 patients), group 2 (20 patients) and group 3 (5 patients). There was no significant difference in age, disease type, gender, etc. among the subjects in each group (P＞0.05).

患者入组标准：符合缺血性脑卒中的诊断标准，20～70岁，病情相对稳定，知情同意接受本临床研究；依从性好。Patient inclusion criteria: meet the diagnostic criteria for ischemic stroke, aged 20 to 70 years, relatively stable condition, informed consent to participate in this clinical study; good compliance.

患者排除标准：(1)复发型脑梗死患者此次发病前mRS评分≥2级；(2)头颅计算机断层扫描(CT)提示颅内出血性疾病(如出血性脑卒中、硬膜外血肿、颅内血肿、脑室出血、蛛网膜下腔出血等)；(3)脑梗死伴意识障碍(NIHSS评分1a项≥1分)、短暂性脑缺血发作、脑动脉炎、脑肿瘤、脑外伤、颅内感染、脑寄生虫病患者；(4)怀疑或确有酒精、药物滥用病史；(5)妊娠、哺乳期妇女或近期计划妊娠以及不愿意采取避孕措施者；(6)预计生存期低于3个月；(7)入组前3个月内参加过其他临床试验者；(8)研究者认为不宜参加本临床试验的患者。Patient exclusion criteria: (1) patients with recurrent cerebral infarction whose mRS score was ≥2 before the onset of the current disease; (2) patients with intracranial hemorrhagic diseases (such as hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc.) on head computed tomography (CT); (3) patients with cerebral infarction accompanied by impaired consciousness (NIHSS score 1a ≥1 point), transient ischemic attack, cerebral arteritis, brain tumor, brain trauma, intracranial infection, and brain parasitic disease; (4) patients with suspected or confirmed history of alcohol or drug abuse; (5) pregnant or lactating women or those who are planning to become pregnant in the near future and those who are unwilling to take contraceptive measures; (6) patients with an expected survival period of less than 3 months; (7) patients who have participated in other clinical trials within 3 months before enrollment; (8) patients who are considered by the researchers to be unsuitable for participation in this clinical trial.

(二)试验方法(II) Test methods

1组的给药方案：Dosage regimen for group 1:

单次脑脊液鞘内注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽4ml和地塞米松5mg组成。每周脑脊液鞘内注射2次，两周为一个疗程，治疗四周。The drug composition for single intrathecal injection of cerebrospinal fluid is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml of cerebroside carnosine and 5mg of dexamethasone. The intrathecal injection of cerebrospinal fluid is performed twice a week, two weeks as a course of treatment, and the treatment is four weeks.

2组的给药方案：Dosage regimen for group 2:

1、单次脑脊液鞘内注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽4ml和地塞米松5mg组成。每周脑脊液鞘内注射2次，两周为一个疗程，治疗四周。1. The drug composition for single intrathecal injection of cerebrospinal fluid is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml of cerebroside carnosine and 5mg of dexamethasone. The cerebrospinal fluid is injected intrathecally twice a week, two weeks as a course of treatment, and the treatment is four weeks.

2、单次穴位注射用的药物组合物由鼠神经生长因子60ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成，临配临用，选取患侧肢体的合谷穴、手三里、手五里、足三里、阳陵泉、阴陵泉、三阴交和阳交穴并选取健侧的合谷穴和足三里穴进行穴位注射。每天穴位注射1次，两周为一个疗程，治疗四周。2. The pharmaceutical composition for single acupuncture point injection is composed of 60ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. It is prepared and used on the spot. The Hegu point, Shousanli point, Shouwuli point, Zusanli point, Yanglingquan point, Yinlingquan point, Sanyinjiao point and Yangjiao point of the affected limb are selected, and the Hegu point and Zusanli point of the healthy side are selected for acupuncture point injection. Acupuncture point injection is performed once a day, two weeks as a course of treatment, and the treatment is for four weeks.

3组的给药方案：Dosage regimen for the three groups:

(1)单次脑脊液鞘内注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、脑苷肌肽4ml和地塞米松5mg组成。每周脑脊液鞘内注射2次，两周为一个疗程，治疗四周。(1) The pharmaceutical composition for single intrathecal injection of cerebrospinal fluid is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 4ml of cerebroside carnosine and 5mg of dexamethasone. The intrathecal injection of cerebrospinal fluid is performed twice a week, with a course of two weeks for a total of four weeks.

(2)单次穴位注射用的药物组合物由鼠神经生长因子60ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成，临配临用，选取患侧肢体的合谷穴、手三里、手五里、足三里、阳陵泉、阴陵泉、三阴交和阳交穴及健侧的合谷穴和足三里穴进行穴位注射。每天穴位注射1次，一周为一个疗程，治疗四周。(2) The pharmaceutical composition for single acupuncture point injection is composed of 60ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. It is prepared and used on the spot. The Hegu point, Shousanli point, Shouwuli point, Zusanli point, Yanglingquan point, Yinlingquan point, Sanyinjiao point and Yangjiao point of the affected limb and the Hegu point and Zusanli point of the healthy side are selected for acupuncture point injection. Acupuncture point injection is performed once a day, one week is a course of treatment, and the treatment is for four weeks.

(3)单次脑脊液鞘内注射用实施例2制得的神经修复细胞蛋白组合物130ug，用2ml生理盐水溶解。每周脑脊液鞘内注射2次，两周为一个疗程，治疗四周。(3) Single intrathecal injection of cerebrospinal fluid: 130ug of the neural repair cell protein composition prepared in Example 2 was dissolved in 2ml of normal saline. The cerebrospinal fluid was injected intrathecally twice a week, with a course of two weeks for a total of four weeks.

疗效评定：使用表1的脑卒中量表和表2的Barthel指数量表(Modified BarthelIndex，MBI)。Efficacy evaluation: The stroke scale in Table 1 and the Modified Barthel Index (MBI) in Table 2 were used.

1组：治疗当天，约60％患者起效。一个疗程的有效率60％和显效率40％。第二个疗程的有效率为80％和显效率60％。Group 1: On the first day of treatment, about 60% of patients responded. The effective rate of one course of treatment was 60% and the marked effective rate was 40%. The effective rate of the second course of treatment was 80% and the marked effective rate was 60%.

2组：治疗当天，约70％患者起效。一个疗程的有效率80％和显效率50％。第二个疗程的有效率为90％和显效率60％。Group 2: On the day of treatment, about 70% of patients responded. The effective rate of one course of treatment was 80% and the marked effective rate was 50%. The effective rate of the second course of treatment was 90% and the marked effective rate was 60%.

3组：治疗当天，约患者80％起效。一个疗程的有效率100％和显效率60％。第二个疗程的有效率为100％和显效率80％。Group 3: On the day of treatment, about 80% of the patients were effective. The effective rate of one course of treatment was 100% and the marked effective rate was 60%. The effective rate of the second course of treatment was 100% and the marked effective rate was 80%.

以上对本发明具体实施方式的描述并不限制本发明，本领域技术人员可以根据本发明作出各种改变或变形，只要不脱离本发明的精神，均应属于本发明权利要求保护的范围。The above description of the specific embodiments of the present invention does not limit the present invention. Those skilled in the art may make various changes or modifications based on the present invention. As long as they do not depart from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.

Claims (10)

1. The application of a pharmaceutical composition in preparing medicines for preventing and treating nervous system diseases, wherein the pharmaceutical composition for preventing and treating nervous system diseases contains a nerve repair medicine and/or a blood circulation improving medicine and an anti-inflammatory medicine;
preferably, the nerve repair drug and/or blood circulation improving drug is selected from any one or combination of murine nerve growth factor, monosialoganglioside (GM 1), cerebroside carnosine, mecobalamin, adenosylcobalamine, vitamin B complex, butylphthalide, cinepazide maleate, edaravone dextroamphetamine, citicoline sodium, ganglioside, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotolepin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebropeptidyl-glycoside, brain protein, and nervonic acid;
preferably, the anti-inflammatory drug is selected from any one or combination of dexamethasone, methylprednisolone, prednisone, methylprednisolone, cortisone, hydrocortisone, prednisone, prednisolone.
2. The use according to claim 1, wherein the pharmaceutical composition for preventing and treating nervous system disorders consists of a pharmaceutical composition for single intrathecal injection of cerebrospinal fluid and a pharmaceutical composition for single acupoint injection.
3. The use according to any one of claims 1-2, wherein the single intrathecal injection of cerebrospinal fluid comprises 15ug-90ug of murine nerve growth factor, 0.5mg-1.0mg of mecobalamin, adenosylcobalamin or vitamin B 12 Or any one of 0.25mg-1.0mg of citicoline, brain glycoside carnosine or monosialoganglioside (GM 1) or any one of 2ml-8ml of compound brain peptide ganglioside or ganglioside 20-40mg and dexamethasone 2mg-5 mg.
4. The use according to any one of claims 1-3, wherein the pharmaceutical composition for single point injection consists of 30ug-90ug of murine nerve growth factor, 0.5mg-1.0mg of mecobalamin, 0.5mg-1.0mg of adenosylcobalamin, 2mg-5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, 2%.
5. The use according to any one of claims 1-4, selecting the Hegu acupoint, the Sanyi, the Wuyi, the Zusanli, the Yanglingquan, the Yinlingquan, the Sanyinjiao and the Yangjiao acupoint of the affected side and selecting the Hegu acupoint and Zusanli acupoint of the healthy side for acupoint injection.
6. The use according to any one of claims 1-5, wherein the cerebrospinal fluid is injected intrathecally or intravenously 2 times per week for a course of two weeks for four weeks.
7. The use according to any one of claims 1 to 6, optionally in combination with any one of physiotherapy, rehabilitation training or a combination thereof, of a pharmaceutical composition for the prevention and treatment of neurological pathologies.
8. The use of any one of claims 1-7, wherein the neurological disorder is selected from any one or combination of stroke, brain trauma and sequelae, spinal cord injury and sequelae, cerebrovascular disease and sequelae, motor neuron disease, cerebral palsy, parkinson's disease, dementia, myelitis sequelae, meningitis sequelae, encephalitis sequelae, brain dysplasia, brain atrophy, ataxia, multiple sclerosis, neuromyelitis optica, multiple system atrophy, sustained plant survival status, delayed brain disease from carbon monoxide poisoning, cranial nerve injury disease, brain tumor and post-operative nerve dysfunction, intrathecal tumor and post-operative nerve dysfunction, neuropathic pain, nerve damage secondary to cervical, thoracic, lumbar vertebra lesions, brain damage secondary to epilepsy.
9. The pharmaceutical composition for preventing and treating a nervous system disorder according to any one of claims 1 to 8, which contains a nerve repair drug and/or a blood circulation improving drug and an anti-inflammatory drug.
10. A therapeutic regimen for the prevention and treatment of a neurological disorder, which comprises the pharmaceutical composition for the prevention and treatment of a neurological disorder according to any one of claims 1 to 8, containing a nerve repair drug and/or a blood circulation improving drug and an anti-inflammatory drug.
CN202311159266.6A 2022-09-09 2023-09-09 Pharmaceutical compositions for preventing and treating neurological lesions and their applications Pending CN117679522A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN202211101347 2022-09-09
CN2022111013476 2022-09-09
CN2022111016934 2022-09-09
CN202211101693 2022-09-09

Publications (1)

Publication Number Publication Date
CN117679522A true CN117679522A (en) 2024-03-12

Family

ID=90127306

Family Applications (6)

Application Number Title Priority Date Filing Date
CN202311159241.6A Pending CN117679520A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial paralysis in sequela stage and application thereof
CN202311159233.1A Pending CN117679518A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating convalescence facial paralysis and application thereof
CN202311159255.8A Pending CN117679521A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial nerve micro-clamping pressure syndrome and application thereof
CN202311159238.4A Pending CN117679519A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating acute facial nerve paralysis and its application
CN202311159266.6A Pending CN117679522A (en) 2022-09-09 2023-09-09 Pharmaceutical compositions for preventing and treating neurological lesions and their applications
CN202311159251.XA Pending CN117679649A (en) 2022-09-09 2023-09-09 Application of radiofrequency devices in the treatment of facial paralysis and associated movements

Family Applications Before (4)

Application Number Title Priority Date Filing Date
CN202311159241.6A Pending CN117679520A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial paralysis in sequela stage and application thereof
CN202311159233.1A Pending CN117679518A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating convalescence facial paralysis and application thereof
CN202311159255.8A Pending CN117679521A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial nerve micro-clamping pressure syndrome and application thereof
CN202311159238.4A Pending CN117679519A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating acute facial nerve paralysis and its application

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN202311159251.XA Pending CN117679649A (en) 2022-09-09 2023-09-09 Application of radiofrequency devices in the treatment of facial paralysis and associated movements

Country Status (2)

Country Link
CN (6) CN117679520A (en)
WO (6) WO2024051844A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024153178A1 (en) * 2023-01-18 2024-07-25 北京达尔文细胞生物科技有限公司 Pharmaceutical composition having early-stage peripheral facial paralysis treatment effect, and use thereof
CN118045071B (en) * 2024-04-15 2024-06-07 苏州沪云新药研发股份有限公司 Combined medicine for treating ischemic cerebral apoplexy and application thereof

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1036973C (en) * 1993-10-14 1998-01-14 宋定邦 Nerve block injection
JP2000501416A (en) * 1996-04-26 2000-02-08 ユニバーシティー オブ オタワ Methods of treatment and drug screening to treat and prevent neuronal disease
JP2005314348A (en) * 2003-05-21 2005-11-10 Mitsubishi Pharma Corp Facial nerve palsy treatment
MX2007012374A (en) * 2005-04-06 2008-02-22 Adamas Pharmaceuticals Inc Methods and compositions for treatment of cns disorders.
GB0916332D0 (en) * 2009-09-17 2009-10-28 Renovo Ltd Medicaments
WO2012132369A1 (en) * 2011-03-25 2012-10-04 国立大学法人鹿児島大学 Viral vector targeting cancer stem cells
CN102631667B (en) * 2012-04-19 2013-10-02 赵廷宝 Nerve regeneration promotion injection and preparation method thereof
CN202682577U (en) * 2012-06-28 2013-01-23 四川旭康医疗电器有限公司 Household multifunctional comprehensive therapeutic apparatus
CN102988403A (en) * 2012-12-06 2013-03-27 祁建春 Injection medicine composition used for treating facial paralysis in acute stage
US20140296948A1 (en) * 2013-03-27 2014-10-02 Hitops Gmbh New therapy of cancer with pulsed radio frequency
CN103638250B (en) * 2013-12-23 2015-08-12 李宣东 One treats prosopoplegic Chinese medicine preparation and preparation method thereof
US20150209390A1 (en) * 2014-01-27 2015-07-30 Snu R&Db Foundation Method and pharmaceutical composition comprising adipose stem cell extract for treating or preventing neurologic disease
CN204233210U (en) * 2014-11-15 2015-04-01 周国明 Full frequency band combined type Wicresoft radio frequency pain therapeutic equipment
CN104587448A (en) * 2015-01-28 2015-05-06 赵廷宝 Method for intrathecally injecting nerve regeneration promoting injection
CN104771602A (en) * 2015-04-17 2015-07-15 刘振亮 Medicine for treating facioplegia and preparation method thereof
CN106265678B (en) * 2016-07-18 2019-06-04 陕西省中医医院 A kind of plaster and preparation method thereof for facial paralysis
CN108743366A (en) * 2018-02-28 2018-11-06 上海衡晟医院投资管理有限公司 The method of biological liquid drugs injection activation auditory nerve
CN209075855U (en) * 2018-09-27 2019-07-09 金泽 Facial paralysis illness oral cavity intramedullary expansion and acupoint stimulation electronic pulse therapeutic instrument
CN111419866A (en) * 2020-03-02 2020-07-17 南通大学 Application of miR-29a-3p in the preparation of drugs for peripheral nerve injury
US11806545B2 (en) * 2020-10-23 2023-11-07 Nextep BV Therapy of eye conditions with pulsed radio frequency
CN113082043A (en) * 2021-04-20 2021-07-09 王化兰 Medicine for treating facial paralysis by traditional Chinese medicine acupoint injection

Also Published As

Publication number Publication date
WO2024051844A1 (en) 2024-03-14
WO2024051846A1 (en) 2024-03-14
CN117679649A (en) 2024-03-12
WO2024051847A1 (en) 2024-03-14
CN117679519A (en) 2024-03-12
WO2024051843A1 (en) 2024-03-14
CN117679518A (en) 2024-03-12
CN117679521A (en) 2024-03-12
CN117679520A (en) 2024-03-12
WO2024051845A1 (en) 2024-03-14
WO2024051848A1 (en) 2024-03-14

Similar Documents

Publication Publication Date Title
Liu et al. Inflammatory response to spinal cord injury and its treatment
CN117679522A (en) Pharmaceutical compositions for preventing and treating neurological lesions and their applications
Xiong et al. Emerging treatments for traumatic brain injury
KR102193175B1 (en) Stem cell-derived exosomes with pain control factors and uses thereof
CN101732348B (en) Application of varicella vaccine inflammation induced rabbit fur extractive in preparing medicaments for treating acute cerebrovascular diseases
WO2018113027A1 (en) Application of bilobalide as synergist in preparation of drugs for preventing cranial nerve injury diseases
CN104394885B (en) The prevention of the nerve ending pain caused by anticancer and/or therapeutic agent
CN107898816A (en) Eye medicinal preparation and its application
WO2013020136A2 (en) Treatment of traumatic brain injury
Santamaría et al. Clinical and neurophysiological changes after targeted intrathecal injections of bone marrow stem cells in a C3 tetraplegic subject
CN113413461A (en) Medicine for resisting senile dementia and its preparing method
KR20180043208A (en) Composition for treating cerebral lesions
EP2734209B1 (en) Intranasal administration of agents with pro-inflammatory activity for the therapy of neurological disorders
Li et al. Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage: phase I clinical trial
CN111511373A (en) Nervous system disease therapeutic agent
KR102414649B1 (en) Erythropoietin-derived peptide, preparation method therefor, and use thereof
US20210023264A1 (en) Use of immune modulators to improve nerve regeneration
Parvin et al. Effects of artemisinin and TSP‑1‑human endometrial‑derived stem cells on a streptozocin‑induced model of Alzheimer’s disease and diabetes in Wistar rats
Wang et al. Research progress on the therapeutic effect of olfactory ensheathing cell transplantation on ischemic stroke
WO2018056412A1 (en) Schwann cell differentiation promoter and peripheral nerve regeneration promoter
TWI736173B (en) Mycelium of liquid culture of antrodia camphorata extract, compounds of mycelium of liquid culture of antrodia camphorata extract, and use thereof for treating ischemic stroke
CN114832067A (en) Cell composition for treating acute stroke and preparation method thereof
CN102988461A (en) Rhodiola rosea injection and preparation method thereof
RU2347578C1 (en) Method for treatment of brain confusion
Ren et al. Clinical Efficacy of Ganglioside Combined with Methylprednisolone in the Treatment of Spinal Cord Injury and Its Effect on Inflammatory Response and Oxidative Stress Factors

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication