CN109966278A - Application of the oxalyl malic acid in the drug of preparation treatment neural cell injury - Google Patents

Application of the oxalyl malic acid in the drug of preparation treatment neural cell injury Download PDF

Info

Publication number
CN109966278A
CN109966278A CN201910269217.5A CN201910269217A CN109966278A CN 109966278 A CN109966278 A CN 109966278A CN 201910269217 A CN201910269217 A CN 201910269217A CN 109966278 A CN109966278 A CN 109966278A
Authority
CN
China
Prior art keywords
disease
cerebral
injury
ischemia
oxalyl
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.)
Granted
Application number
CN201910269217.5A
Other languages
Chinese (zh)
Other versions
CN109966278B (en
Inventor
彭军
罗秀菊
刘为宁
李悦琪
任凯迪
田静
彭靖杰
刘斌
付四海
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.)
Central South University
Original Assignee
Central South University
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 Central South University filed Critical Central South University
Priority to CN201910269217.5A priority Critical patent/CN109966278B/en
Publication of CN109966278A publication Critical patent/CN109966278A/en
Application granted granted Critical
Publication of CN109966278B publication Critical patent/CN109966278B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Psychology (AREA)
  • Emergency Medicine (AREA)
  • Obesity (AREA)
  • Psychiatry (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Hospice & Palliative Care (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to application of the oxalyl malic acid in the drug of preparation treatment neural cell injury.Oxalyl malic acid is used to treat ischemical reperfusion injury, especially treatment brain tissue neuropathy can significantly mitigate cerebral ischemia/reperfusion injury more particularly to the protective effect of cerebral arterial thrombosis, reduce cranial nerve cell damage and improve nerve cell function.

Description

Application of the oxalyl malic acid in the drug of preparation treatment neural cell injury
Technical field
The present invention relates to application of the oxalyl malic acid in the drug of preparation treatment neural cell injury, belong to biological medicine Field.
Background technique
Ischemic stroke is to seriously endanger the common and frequently-occurring disease of human health, has become first in the whole world and disables and third The disease incidence of lethal reason, cerebral arterial thrombosis accounts for about the 70-80% of cerebrovascular disease.
Cerebral ischemia and free radical be excessively formed, toxicity of excitatory amino acid effect, intracellular calcium overload, inflammatory reaction Etc. number of mechanisms it is related, no matter which kind of mechanism, final final result can all cause nerve cell death, function destroy, cerebral infarction stove It is formed.The mode of cell death mainly has necrosis and two approach of apoptosis.Traditional view thinks that necrosis is a kind of random, meaning Outer and not modulated passive death pathways, and apoptosis is then a kind of active death way by tight control.Nearest Studies have shown that necrosis is also by various signal path tight controls, referred to as modulability necrosis, including gangrenosum acne apoptosis (necroptosis), the necrosis etc. that CypD is relied on.Wherein, the gangrenosum acne apoptosis that RIPK1/RIPK3/MLKL is relied on most is closed Note.Studies have shown that the gangrenosum acne apoptosis that RIPK1/RIPK3/MLKL is relied on is present in a variety of quinolin-eta diseases, including the heart Flesh infarct and cerebral arterial thrombosis.Therefore, the gangrenosum acne apoptosis for inhibiting RIPK1/RIPK3 to rely on has become mitigates ischemic at present The effective way of cerebral apoplexy nerve cell death.Document report, RIPK1 inhibitor necrostatin-1 (Nec-1) can be reduced small Mouse cerebral ischemia, improves nervous function, and the effect and the gangrenosum acne apoptosis of inhibition nerve cell are closely related.However, Nec-1 It only is used for zoopery as instrument medicine, is clinically there is no at present for RIPK1/RIPK3/MLKL drug for treating ischemic Cerebral apoplexy also has no the report in oxalyl malic acid treatment ischemic cerebral apoplexy or neural cell injury.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides oxalyl malic acid in the drug of preparation treatment neural cell injury Application.
The structural formula of oxalyl malic acid of the present invention is shown below:
Molecular formula are as follows: C6H3O8；Molecular weight are as follows: 272.05.
Further, the nerve cell includes central nervous system disease associated neural cells.
Further, the central nervous system disease includes traumatic central nervous system damage, cerebral injury, spinal cord damage Wound, cerebral apoplexy, neurodegenerative disease, Alzheimer disease, Huntington disease, dementia, amyotrophic lateral sclerosis, Parkinson's disease, Multiple sclerosis, diabetic neuropathy, spinocerebellar ataxia, fahr disease, menke disease, hepatolenticular degeneration, cerebral ischemia, Prion disease, Frontotemporal dementia, dementia with Lewy body, the degeneration of cortical basal portion, stein-leventhal syndrome, multi-system atrophy and something lost Transmissibility spastic paraplegia.
Further, the cerebral apoplexy includes cerebral arterial thrombosis and/or hemorrhagic apoplexy.
Further, the cerebral arterial thrombosis includes cerebral ischemia/reperfusion injury.
Further, the ischemia/reperfusion injury further includes myocardial ischemia/reperfusion injury, hepatic ischemia/Reperfusion injury One or more of wound, renal ischemia-reperfusion injury, ischemia of lung/reperfusion injury.
Further, the drug can be prepared into acceptable agent in any one pharmacy according to known technique Type, such as oral agents, injection, tablet, capsule, granule, powder, oral solution or dripping pill, preferably oral agents.
Further, the dosage form of the drug is oral agents.
Optionally, the administration mode in the application is subcutaneous injection, intravenous injection, intramuscular injection, oral administration or glutinous Film administration.
Optionally, the administration mode in the application is oral administration.
Experiments show that oxalyl malic acid energy specific downregulation phosphorylation MLKL is horizontal, inhibit nerve cell Downright bad sample apoptosis significantly reduces cerebral ischemia Infarction volume and Neurobiology scoring, reduces cranial nerve cell death and improves mind Through cell function.Therefore, oxalyl malic acid can be applied to the drug of preparation treatment ischemia/reperfusion injury.
Experiments show that oxalyl malic acid significantly reduces cerebral ischemia Infarction volume and Neurobiology scoring, It reduces cranial nerve cell death and improves nerve cell function, it is thin to can be applied to cranial nerve caused by preparation central nervous system disease Born of the same parents are impaired and maladjusted nervous system, the central nervous system disease include traumatic central nervous system damage, cerebral injury, ridge Marrow damage, neurodegenerative disease, Alzheimer disease, Huntington disease disease, dementia, amyotrophic lateral sclerosis, Parkinson's disease, Multiple sclerosis, diabetic neuropathy, different type spinocerebellar ataxia, fahr disease, menke disease, hepatolenticular degeneration, Cerebral ischemia, prion disorder, Frontotemporal dementia, dementia with Lewy body, the degeneration of cortical basal portion, stein-leventhal syndrome, polyphyly System atrophy and hereditary spastic paraplegia.
The present invention expands the indication of oxalyl malic acid, is applicable to ischemia/reperfusion injury；With drug administration by injection mode It compares, oral administration can be used in the present invention, and easy to operate, irritation is small, enhances the compliance of patient.
There is not been reported for treating cerebral apoplexy for oxalyl malic acid.The present invention is used for oxalyl malic acid to treat rat for the first time Cerebral arterial thrombosis model, discovery oxalyl malic acid can lower phosphorylation MLKL level in rat cerebral tissue, reduce rat cerebral infarction Dead volume reduces neural cell injury and improves neurology function.First demonstration that oxalyl malic acid can be used for treating Cerebral arterial thrombosis, mechanism inhibit neuronal cell death apoptosis and play a role by lowering MLKL phosphorylation level. The present invention expands oxalyl malic acid indication range, it was found that its new mechanism of drug action.Cerebral arterial thrombosis is clinical normal See disease, oxalyl malic acid has broad application prospects.
The research discovery oxalyl malic acid of the present inventor has the function of new, energy specific downregulation phosphorylation MLKL level, Inhibit meronecrosis apoptosis.
In short, oxalyl malic acid is used to treat brain tissue neuropathy by the present invention, especially to the guarantor of cerebral arterial thrombosis Shield effect, can significantly mitigate cerebral ischemia/reperfusion injury.
Detailed description of the invention
Fig. 1: operation consent 15 minutes administrations, A- rat cerebral tissue TTC dyeing and Infarction volume measurement, B- rat nerve function It can scoring.
Specific embodiment
Zoopery: protective effect of the oxalyl malic acid to cerebral arterial thrombosis
Implement drug: oxalyl malic acid is purchased from Reagent Company.
By oxalyl malic acid physiological saline solution.
Experimental animal: the healthy male SD rat of 250~300g of weight.By experimental animal in 25 DEG C of temperature, relative humidity 60%, free water, raise in environment at regular time and quantity one week, then press requirement of experiment, administration group oral administration.
Modeling method: ischemia-reperfusion injury model is prepared with brain Middle cerebral artery occlusion (MCAO) method.Step is such as Under: (1) it separates external carotid artery (CCA), separates upwards left external carotid artery (ECA) and internal carotid (ICA)；(2) temporary with ophthalmic tweezers When folder close ECA and ICA, and ligature CCA proximal part；(3) a spare silk thread having knotting is placed in CCA distal end, under this line An osculum is cut at end, and bolt line is inserted into internal carotid, tightens silk thread, decontrols the artery clamp on ECA and ICA, send bolt line along ICA To encephalic；(4) power that is hampered and stop, counted from CCA crotch, insertion depth is about 18~20mm；It (5), will after ischemic 120min Bolt line is extracted, and skin of sewing it up, Reperfu- sion post-processes animal for 24 hours.
Model success judgment criteria is commented using the neurologic impairment that Longa " 5 point-score " damages rat cerebral ischemia Point.0 point: impassivity defective symptom；1 point: right fore cannot stretch completely；2 points: rotating to the right；3 points: walking is toppled over to the right； 4 points: it spontaneous cannot walk, the loss of consciousness.1~4 point is valid model.
Rat brain TTC dyeing and Infarction volume measurement.After rat anesthesia, brain is taken out rapidly, removes olfactory bulb and hindbrain, from Antinion starts to cut 4 coronal brain pieces, and thickness about 2.0mm is placed at once in 1%TTC solution, and 37 DEG C are protected from light incubation 30min.Then It is impregnated and is fixed with 10% paraformaldehyde solution.White is presented in infarcted region, and non-infarcted region presents red.By every group of brain piece marshalling After be scanned.The infarct size that ImageJ measures each brain piece is reapplied, according to formula: Infarction volume=[(each positive infarct The sum of the sum of area+each reverse side infarct size)/2] × every thickness, same method calculates full brain volume.
Experimental group: experimental animal is randomly divided into 4 groups, it may be assumed that
Control group (control group): without any processing.
Sham-operation group (sham group): bolt line is not inserted into after separating blood vessel.
Ischemia/reperfusion group (I/R): cerebral ischemia 2h, Reperfu- sion is for 24 hours.
Oxalyl malic acid+Cerebral Ischemia/Reperfusion group (OMA+I/R): 15 minutes stomach-filling oxalyl malic acid of operation consent (dosage: 10mg/kg), then cerebral ischemia 2h, Reperfu- sion is for 24 hours.
Testing index: rat nerve function score and Infarction volume measurement.
Experimental result
Influence of the oxalyl malic acid to rat cerebral infarction volume and nervous function
Shown in A in Fig. 1, I/R group has apparent pale infarct stove, and operation consent gives oxalyl malic acid group rat cerebral infarction Dead stove is reduced significantly, hence it is evident that is alleviated cerebral ischemia (p < 0.01).Scheme B, apparent nerve fortune occurs in cerebral ischemia group (I/R) rat Dynamic dysfunction, and oxalyl malic acid can obviously improve neurologic impairment symptom (p < 0.01).
But this patent is not limited to cerebral ischemia/reperfusion injury, because the heart, liver and renal ischemia-reperfusion injury equally exist Downright bad sample apoptosis, therefore the medicine is equally applicable to the treatment heart, liver, kidney and ischemia of lung/reperfusion injury.In addition, central nervous system Downright bad sample apoptosis up-regulation causes cranial nerve cell impaired and maladjusted nervous system in disease, therefore oxalyl malic acid is also applied for controlling Treat these central system disorders.

Claims (8)

1. application of the oxalyl malic acid in the drug of preparation treatment neural cell injury.
2. application according to claim 1, which is characterized in that the nerve cell includes central nervous system disease correlation Nerve cell.
3. application according to claim 2, which is characterized in that the central nervous system disease includes wound sexual centre mind Through system injury, cerebral injury, spinal cord injury, cerebral apoplexy, neurodegenerative disease, Alzheimer disease, Huntington disease, dementia, Amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, diabetic neuropathy, spinocerebellar ataxia, fahr disease, Menke disease, hepatolenticular degeneration, cerebral ischemia, prion disease, Frontotemporal dementia, dementia with Lewy body, the degeneration of cortical basal portion, progressive Supranuclear paralysis, multi-system atrophy and hereditary spastic paraplegia.
4. application according to claim 3, which is characterized in that the cerebral apoplexy includes cerebral arterial thrombosis and/or bleeding Property cerebral apoplexy.
5. application according to claim 4, which is characterized in that the cerebral arterial thrombosis includes Cerebral Ischemia/Reperfusion damage Wound.
6. application according to claim 5, which is characterized in that the ischemia/reperfusion injury further includes myocardial ischemia/again One or more of perfusion injury, During Hepatic Ischemiareperfusion Injury, renal ischemia-reperfusion injury, ischemia of lung/reperfusion injury.
7. application according to claim 1-6, which is characterized in that the drug can be prepared into can in pharmacy With any one dosage form of receiving, further, the dosage form includes oral agents, injection, tablet, capsule, granule, dissipates Agent, oral solution, dripping pill, preferably oral agents or injection.
8. application according to claim 7, which is characterized in that the dosage form of the drug is oral agents.
CN201910269217.5A 2019-04-04 2019-04-04 Application of oxalyl malic acid in preparation of medicine for treating nerve cell injury Active CN109966278B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910269217.5A CN109966278B (en) 2019-04-04 2019-04-04 Application of oxalyl malic acid in preparation of medicine for treating nerve cell injury

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910269217.5A CN109966278B (en) 2019-04-04 2019-04-04 Application of oxalyl malic acid in preparation of medicine for treating nerve cell injury

Publications (2)

Publication Number Publication Date
CN109966278A true CN109966278A (en) 2019-07-05
CN109966278B CN109966278B (en) 2021-09-24

Family

ID=67082765

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910269217.5A Active CN109966278B (en) 2019-04-04 2019-04-04 Application of oxalyl malic acid in preparation of medicine for treating nerve cell injury

Country Status (1)

Country Link
CN (1) CN109966278B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112675159A (en) * 2021-01-12 2021-04-20 杭州师范大学 Application of L-malic acid in preparing medicine for preventing and treating liver ischemia reperfusion injury

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106714814A (en) * 2014-06-27 2017-05-24 S生物医药公司 Composition for treating ischemic diseases or neurogenic inflammation, containing, as active ingredient, neural progenitor cells or secretome thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106714814A (en) * 2014-06-27 2017-05-24 S生物医药公司 Composition for treating ischemic diseases or neurogenic inflammation, containing, as active ingredient, neural progenitor cells or secretome thereof

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BY ANITA PATT ET AL.: "Iron Depletion or Chelation Reduces Ischemia/Reperfusion-Induced Edema in Gerbil Brains", 《JOURNAL OF PEDIATRIC SURGERY》 *
FESTA, M ET AL.: "Oxalomalate, a competitive inhibitor of aconitase, modulates the RNA-binding activity of iron-regulatory proteins", 《BIOCHEMICAL JOURNAL》 *
REGAN, RAYMOND F ET AL.: "Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide", 《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》 *
SANTAMARIA, R ET AL.: "Induction of ferritin expression by oxalomalate", 《BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH》 *
庹清章: "Tau介导的铁转运在局灶性脑缺血再灌注损伤中的作用", 《华中科技大学 硕士学位论文 2016年》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112675159A (en) * 2021-01-12 2021-04-20 杭州师范大学 Application of L-malic acid in preparing medicine for preventing and treating liver ischemia reperfusion injury

Also Published As

Publication number Publication date
CN109966278B (en) 2021-09-24

Similar Documents

Publication Publication Date Title
Mancuso et al. Resveratrol improves motoneuron function and extends survival in SOD1G93A ALS mice
AU2008292407B2 (en) Prophylactic or alleviating agent for peripheral nerve disorder induced by anti-cancer agent
Yu et al. Anticonvulsant and anti-apoptosis effects of salvianolic acid B on pentylenetetrazole-kindled rats via AKT/CREB/BDNF signaling
CA3000985C (en) Method for treating neurodegenerative diseases
EP2385835B1 (en) Use of deuterium oxide for treating viral diseases of the eye
JP6085806B2 (en) Use of an extract from rabbit skin inflamed by vaccinia virus in the manufacture of a medicament for the treatment of acute cerebrovascular disease
Chen et al. Tert-butylhydroquinone enhanced angiogenesis and astrocyte activation by activating nuclear factor-E2-related factor 2/heme oxygenase-1 after focal cerebral ischemia in mice
EP3154551B1 (en) The use of dextran sulfate having an average molecular weight below 10000 da for inducing angiogenisis in a subject
CN109966278A (en) Application of the oxalyl malic acid in the drug of preparation treatment neural cell injury
CN111511373A (en) Remedies for nervous system diseases
CN116688025A (en) Use of water-soluble tomato concentrate in preparation of composition for treating cerebral ischemia-reperfusion injury
RU2509565C2 (en) METHOD FOR PREPARING FRACTION 4 (APD-f4) AND FRACTION 5 (APD-f5) ADAPTOGENIC DOROGOV&#39;S PREPARATION
CN115919835A (en) Application of procyanidine in preparation of medicine for promoting central nervous system inflammatory demyelination regeneration
KR20150085578A (en) Pharmaceutical composition comprising adipose stem cell extract for treating or preventing neurologic disease
Zou et al. Mechanism of scutellarin inhibition of astrocyte activation to type A1 after ischemic stroke
CN109999177A (en) Application of the polymyxin in preparation treatment neural cell injury drug
RU2825666C2 (en) Therapeutic agent for treating nervous system disease
WO2023115294A1 (en) Use of naoxintong preparation in preparation of drug for treating non-alcoholic fatty liver disease
US20220202887A1 (en) Neuroprotective phyllanthus emblica-containing compositions and methods
EP3362059B1 (en) New combination therapies for treating neurological damage
Jadeja et al. Fumaric acid esters as potential therapies for treating degenerative retinal disease
Gillmann et al. Neuroprotection and neuroenhancement
CN112107587A (en) Pharmaceutical composition for promoting regeneration of neuron axons and application thereof
KR20160146625A (en) Pharmaceutical composition comprising adipose stem cell extract for treating or preventing neurologic disease
Yaoa et al. Enhancing mitophagy by ligustilide through BNIP3-LC3 interaction attenuates

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant