CN109528746A - Application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia - Google Patents

Application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia Download PDF

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Publication number
CN109528746A
CN109528746A CN201910024767.0A CN201910024767A CN109528746A CN 109528746 A CN109528746 A CN 109528746A CN 201910024767 A CN201910024767 A CN 201910024767A CN 109528746 A CN109528746 A CN 109528746A
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China
Prior art keywords
isoorientin
new zealand
senile dementia
drug
application
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Pending
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CN201910024767.0A
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Chinese (zh)
Inventor
张振强
袁永
谢治深
付钰
蒋亚丽
宋军营
曾华辉
马金莲
李中华
孙丽敏
苏运芳
高改
赵建平
张俊霞
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Henan University of Traditional Chinese Medicine HUTCM
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Henan University of Traditional Chinese Medicine HUTCM
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Priority to CN201910024767.0A priority Critical patent/CN109528746A/en
Publication of CN109528746A publication Critical patent/CN109528746A/en
Pending legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Neurology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia.Senile dementia is a kind of using the retrogression pathological changes of central nervous system primary, progressive as the disease of main feature, and clinical manifestation is cognition and the irreversibility deterioration of memory function, and the A β for being primarily due to intracerebral over-deposit causes to damage to neuron.It is a discovery of the invention that New Zealand's Isoorientin can protect neural cell injury caused by A β, thus have exploitation at the prospect of anti senile dementia drug.

Description

Application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia
Technical field
The invention belongs to field of medicaments, are related to the new application of known compound, and in particular to prepared by New Zealand's Isoorientin Prevent and treat the application in the drug of senile dementia.
Background technique
Alzheimer's disease (Alzheimer ' s disease, AD) is also known as senile dementia, is one kind with progressive intelligence The disease that degeneration and neuron loss are characterized.The over-65s old man of the whole world about 5-10% suffers from the disease at present, there are about 35000000 patients.Life cycle of the Disease after making a definite diagnosis only has 3 to 9 years, oneself is through becoming after cardiovascular and cerebrovascular disease and cancer The third-largest killer of senior health and fitness is threatened later.AD is a kind of with central nervous system primary, the degenerative disease of progressive Become the disease of main feature, clinical manifestation is cognition and the irreversibility deterioration of memory function, and major pathogenetic factor is intracerebral The damage of A β (amyloid beta) neuron of over-deposit.It is many about the etiology and pathology research of AD in recent years, now compare Generally acknowledged pathological characteristics, which are A β, causes central nervous system in the neurotoxicity that the senile plaque that intracerebral over-deposit is formed generates Cholinergic neuron mortality, lose etc..Therefore inhibit the deposition of A β or mitigate damage of the A β to neuronal cell It has become a hot topic of research and one of the Main way of drug development.
New Zealand's Isoorientin is a kind of flavone c-glycoside class natural products, there is no New Zealand's Isoorientin silly with anti-ageing year at present The report of slow-witted effect.
Summary of the invention
The purpose of the present invention is to provide application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia.
Above-mentioned purpose of the invention is realized by following technical solution:
Application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia.
Application of the pharmaceutically acceptable salt of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia.
It is a kind of prevent and treat senile dementia pharmaceutical preparation, using New Zealand's Isoorientin or its pharmaceutically acceptable salt as drug Pharmaceutically acceptable preparation formulation is made in active constituent.
Preferably, the preparation formulation is tablet, capsule, injection or oral solution.
The utility model has the advantages that it is main that senile dementia, which is a kind of retrogression pathological changes with central nervous system primary, progressive, The disease of feature, clinical manifestation are cognition and the irreversibility deterioration of memory function, are primarily due to the A β couple of intracerebral over-deposit Neuron causes to damage.It is a discovery of the invention that New Zealand's Isoorientin can protect neural cell injury caused by A β, thus has and open Send out into the prospect of anti senile dementia drug.
Specific embodiment
One, experimental material
25-35Purchased from Beijing Bo Aosen Bioisystech Co., Ltd;Dimethyl sulfoxide (DMSO) is raw purchased from Shanghai Mike woods Change Science and Technology Ltd.;Thiazolyl blue (MTT) is purchased from Dalian U.S. logical sequence Technology Co., Ltd.;New Zealand's Isoorientin is general purchased from Chengdu Fei De Bioisystech Co., Ltd;Fetal calf serum is purchased from the biotech inc Zhejiang Tian Hang;RPMI-1640 culture medium Purchased from Hyclone company.
Condensed state A β25-35Preparation: by 1mg A β25-35It is first dissolved in appropriate sterile dd H2In O, it is raw to add medical aseptic Reason salt water makes A β25-35Final concentration of 1mM, 37 DEG C of water-baths are incubated for 7d.
Two, experimental method
1, cell culture
The rat neurogliocytoma cells C6 cell strain for being stored in liquid nitrogen frozen is taken out, is immediately placed in 37 DEG C of water-baths and vibrates It after melting to cell, is transferred in the centrifuge tube that culture medium has been added, 5min is centrifuged with 1000rpm, discards supernatant liquid, be added a small amount of Culture medium and gently pressure-vaccum is uniform, culture medium are containing 10% fetal calf serum, 1% dual anti-RPMI-1640 culture medium, by cell Suspension moves into culture dish, in 37 DEG C, 5%CO2, cultivate under the conditions of saturated humidity.
2, the preparation of cell model
It is 2.0 × 10 that concentration, which is made, in the C6 cell of logarithmic growth phase5The cell suspension of a/mL is inoculated in 96 orifice plates, Every 100 μ L of hole after culture for 24 hours, is handled, every group of 5 multiple holes according to following grouping:
Control group: it is changed to fresh culture and continues to cultivate 3h;
25-35Group (model group): it is changed to fresh culture and continues to cultivate 3h;
Doneppezil Hydrochloride group (positive drug group): it is changed to the fresh culture containing 20 μM of Doneppezil Hydrochlorides and continues to cultivate 3h;
New Zealand's Isoorientin group: it is changed to the fresh culture containing 5,10,20 μM of New Zealand's Isoorientins and continues to cultivate 3h.
Continue after cultivating 3h according to above-mentioned grouping, A β25-35Group, Doneppezil Hydrochloride group, the addition of New Zealand's Isoorientin group are eventually The condensed state A β that concentration is 10 μM25-35, isometric solvent is added in control group, and after continuing culture 18h, 20 μ L MTT of each group addition are molten Liquid (concentration 5mg/mL) continues at 37 DEG C to cultivate 4h.
Continue after cultivating 4h, careful inhale abandons supernatant in hole, and 150 μ L DMSO are added in every hole, shake 10min, fills crystallization Divide dissolution;490nm wavelength is selected, each hole absorbance value (OD value) is measured on enzyme-linked immunosorbent assay instrument, takes 5 multiple holes OD values flat Mean, calculates cell survival rate, and control group is denoted as 100%.
4, data processing and inversion
Using SPSS19.0 software, more comparison among groups are examined using one-way analysis of variance, are compared two-by-two between group and are examined using q It tests.It is that difference is statistically significant with P < 0.05.
Three, experimental result
Group of cells survival rate (note: compared with the control group as shown in table 1#P < 0.05,##P < 0.01,###p<0.001;With A β25-35Group compares * p < 0.05, p < 0.001 * * p < 0.01, * * *).
1. New Zealand's Isoorientin of table is to A β25-35The influence of the cellular damage of induction
Compared with the control group, A β25-35Group cell survival rate significantly reduces, and illustrates cell modeling success;With A β25-35Group phase Than Doneppezil Hydrochloride group, New Zealand's Isoorientin group cell survival rate significantly increase.Doneppezil Hydrochloride is U.S.'s food and medicine Object management board (FDA) approval for treating the drug of Alzheimer disease, 20 μM about make cell survival rate promote 4%, and 5 μM New Zealand's Isoorientin just can make cell survival rate promote 5%, and as dosage increases protective effect enhancing, 10 μM can about promote 8%, 20 μM about make survival rate promote 14%, and have statistical difference.Cell Proliferation is promoted to cause in order to exclude New Zealand's Isoorientin False positive, intervene influence of the lower New Zealand's Isoorientin to cell viability We conducted no A β and test, as a result such as 2 institute of table Show, New Zealand's Isoorientin under 5,10,20 μM of concentration on cell viability without influence (P ﹥ 0.05), this is the result shows that New Zealand herds Chaste tree glycosides does not cause cell Proliferation.
Influence of the 2. New Zealand's Isoorientin of table to C6 cell Proliferation vigor
Therefore, consolidated statement 1,2 results are believed that New Zealand's Isoorientin can protect neural cell injury caused by A β, With exploitation at the prospect of anti senile dementia drug.

Claims (4)

1. application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia.
2. application of the pharmaceutically acceptable salt of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia.
3. it is a kind of prevent and treat senile dementia pharmaceutical preparation, using New Zealand's Isoorientin or its pharmaceutically acceptable salt be drug work Property ingredient, is made pharmaceutically acceptable preparation formulation.
4. pharmaceutical preparation according to claim 3, the preparation formulation is tablet, capsule, injection or oral solution.
CN201910024767.0A 2019-01-10 2019-01-10 Application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia Pending CN109528746A (en)

Priority Applications (1)

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CN201910024767.0A CN109528746A (en) 2019-01-10 2019-01-10 Application of New Zealand's Isoorientin in the drug of preparation prevention and treatment senile dementia

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013079624A1 (en) * 2011-11-29 2013-06-06 Amino Up Chemical Co., Ltd. Composition comprising vicenin-2 having a beneficial effect on neurological and/or cognitive function

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013079624A1 (en) * 2011-11-29 2013-06-06 Amino Up Chemical Co., Ltd. Composition comprising vicenin-2 having a beneficial effect on neurological and/or cognitive function

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
耿丽颖: "《中国优秀硕士学位论文全文数据库(电子期刊)》", 31 May 2017 *

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Application publication date: 20190329