CN107693530A - Aurantiamarin and/or aurantiin are preparing the application in improving cognition dysfunction medicine - Google Patents
Aurantiamarin and/or aurantiin are preparing the application in improving cognition dysfunction medicine Download PDFInfo
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Abstract
The present invention relates to aurantiamarin and/or aurantiin to prepare the application in improving cognition dysfunction medicine.
Description
Technical field
The present invention relates to aurantiamarin and/or aurantiin to prepare the application in improving cognition dysfunction medicine.
Background technology
Senile dementia is to occur to produce in the brain disorder characterized by progressive dementia in senilism phase and senescence phase
Intelligence damage syndrome.Including senile dementia, be called Alzheimer's disease (Alzheimer disease, abbreviation AD) and
Cerebral vascular dementia (Vascular dementia, abbreviation VD) two classes.Wherein AD is a kind of primary for betiding the elderly
Central nervous system regression disease；VD is the dementia caused by cerebral lesion caused by cerebrovascular disease.The VD cause of disease is related to two
Individual aspect, i.e. cerebrovascular disease and hazards.Hazards include hazards (hypertension, high fat of blood, the heart of cerebrovascular disease
Disease, diabetes, universality artery sclerosis, smoking), palsy, patient with ischaemic leukoaraiosis lesion, advanced age and schooling it is low etc..
According to incompletely statistics, the ratio that severe senile dementia is suffered from over-65s crowd is 5%~8%, and to 80
Year, this ratio just rise to 15%~20%.China's patients with Alzheimer disease has 6,000,000 people at present, accounts for global patient's sum
1/3, the people of annual neopathy about 1,800,000 extremely forgets 105.6 ten thousand people, morbidity situation very severe, it has also become modern society causes
The main reason for the elderly is disabled and can not live on one's own life, is one of four big diseases of serious threat senior health and fitness.
Regrettably, senile dementia is treated so far still without good plan, is had or i.e. by face on domestic and international market at present
The medicine in city is mainly cholinergic drug, common mainly anticholinesterase.Tacrine (trade name group can cause) is the
A kind of medicine for being approved for senile dementia treatment, but the hepatotoxicity of the medicine is larger, is not made by clinic gradually
With.Donepezil (trade name Aricept) is safer compared with Tacrine, and effectively preceding clothes are slept in general recommendations at night, but to losing
The patient of dormancy then suggests that daytime takes medicine.Rivastigmine-hydrogentartrate (trade name Exelon) is also the important of the elderly's cognitive disorder
Medicine.Domestic and international clinical trial also prompts cognition symptom and daily activities of the medicine to dementia patients to have necessarily
Improvement result, and few side effects.Huperzine (trade name double benefit flat) is Shanghai institute of materia medica of the Chinese Academy of Sciences from serrate clubmoss herb
A kind of alkaloid of extraction, is a kind of high selectivity anticholinesterase in (Huperzia serrata.), is had necessarily
Improve memory and the effect of cognitive function.
Senile dementia dialectical treatmert, is divided into five card types by the traditional Chinese medical science from organic conception：1. kidney deficiency marrow subtracts card；2. gas
Stagnant syndrome of blood stasis；3. turbid phlegm blocking the clear orifices is demonstrate,proved；4. deficiency of YIN of both the heart and liver is demonstrate,proved；5. syndrome of deficiency of both heart and spleen.Each syndrome has symptom group quantization table respectively again,
Can be divided into it is light, in, weight Three Estate, and combine brain electrical activity mapping, rheoencephalogram, skull CT scanning, gait test, cerebrospinal fluid second
The lab index such as acetylcholinesterase and Protein tau content is assessed.
At present, etiology and pathology is not yet clear about senile dementia in neuroscience field in the whole world, and senile dementia moves
Thing model is established and drug research method is still not mature enough.Experimental animal often uses mouse or rat, and method is optional：1. naturally-aged
Animal model；2. the ozone that mouse sucks high concentration for a long time causes brain aging animal model；3. give mouse long term injections D- galas
Sugar causes aging model；4. senescence accelerated mouse model (SAMP series), damages the experimental AD animals mould of cholinergic nerve of centrum unit
Type；5. chemicals overall applicability causes dysmnesia model；7. transgenic mice simulation SDAT type Model of Dementia etc..Observational technique
It is optional：Darkness avoidance test, shuttle method, step dow n test, water maze method, electric maze method etc. can preferably evaluation experimental animal learning and memory
With space exploration ability.Wherein, it is the ability of learning and memory for testing rat in the recent period with long term to keep away dark shuttle experiment purpose.Morris
The purpose of water maze laboratory is test AD rat models ability of learning and memory and space exploration ability.
The structure of aurantiamarin is：
Molecular formula：C28H34O15, thin dendroid acicular crystal (precipitating gained in pH6~7).M.p.258~262 DEG C, [α]D 20-
76 ° (c 2, pyridines).Methanol and hot glacial acetic acid are slightly dissolved in, is practically insoluble in acetone, benzene and chloroform, and is soluble in diluted alkaline and pyrrole
Pyridine.
The structure of aurantiin is：
Molecular formula：C27H32O14, it is two water things to be dried at 110 DEG C to weights, m.p.171 DEG C.[α]D 19- 82 ° (ethanol).1
Gram 1000ml water is dissolved in, acetone, ethanol, hot acetic acid and hot water is dissolved in, insoluble in ether, hexane and chloroform.
Recorded according to CN1704065A, aurantiamarin and/or aurantiin can be used as bitters, diaphoretic, also with norcholesterol,
Acute/chronic bronchitis, promotion WeiDongLi Capsule effect are treated, but not yet finds that there is improvement to recognize for aurantiamarin and/or aurantiin at present
Effect in dysfunction medicine.
The content of the invention
Applicant has been surprisingly found that aurantiamarin and/or aurantiin are preparing the application effect in improving cognition dysfunction medicine
Fruit is notable.
The first aspect of the present invention, there is provided aurantiamarin and/or aurantiin are in improvement cognition dysfunction medicine is prepared
Using.
One of which preferred embodiment, the cognition dysfunction are senile dementia.
One of which highly preferred embodiment, the senile dementia are Alzheimer's disease.
One of which highly preferred embodiment, the senile dementia are cerebrovascular dementia.
One of which preferred embodiment, the aurantiamarin and aurantiin, mass ratio 1:9-9:1.
The second aspect of the present invention, there is provided a kind of preparation method of aurantiamarin and/or aurantiin, the aurantiamarin and/or
Aurantiin be from the medicinal material containing aurantiamarin and/or aurantiin in extract and obtain.
One of which preferred embodiment, the medicinal material containing aurantiamarin and/or aurantiin can be the dried immature fruit of citron orange, Fructus Aurantii,
Citrus, lemon, grape fruit, Exocarpium Citri Rubrum, orange etc..
One of which preferred embodiment, the extracting method are：Fine medicinal material powder, extracted with ethanol, extract solution recovery
Ethanol adds distilled water, successively with petroleum ether, ethyl acetate and extracting n-butyl alcohol, extracting n-butyl alcohol position is through dense to without alcohol taste
After contracting is dried, upper D101 types macroporous resin column, successively with water, 25% ethanol, 50% ethanol and 95% ethanol elution, 50% ethanol
The total glycosides of mixing of aurantiamarin and/or aurantiin must be contained after the elution concentrated drying in position, through the isolated orange peel of silica gel column chromatography
Glycosides and/or aurantiin monomer sterling.
Neohesperidin of the present invention can also be according to Rosenmund (Rosenmund, Ber., 61,2608 (1958))
And the method for Zemlen, Bognar (Ber., 75,648 (1942)) description or other chemical methodes are synthesized to obtain.
The third aspect of the present invention, there is provided a kind of pharmaceutical composition, include aurantiamarin and/or aurantiin and at least one medicine
Use carrier.
Can use this area conventional method be prepared into various formulations, as granule, tablet, capsule, injection, pill,
Gel, extract formulation, syrup, medicinal tea etc..
The fourth aspect of the present invention, there is provided a kind of pharmaceutical preparation, include aurantiamarin and/or aurantiin.
One of which preferred embodiment, the pharmaceutical preparation are oral formulations.
One of which preferred embodiment, the dosage when pharmaceutical preparation uses for 20-300mg/ people/time,
1-3 times daily.
The advantageous effects of the present invention：
1st, aurantiamarin and/or aurantiin improve significantly to the spatial cognition obstacle of AD rats.
2nd, aurantiamarin and/or aurantiin can significantly improve brain tissue SOD activity, while reduce MDA activity.
3rd, aurantiamarin and/or aurantiin improve significantly to the memory dysfunction of AD rats.
4th, aurantiamarin and/or aurantiin have obvious suppression to make to experimental AD rat cerebral cortex glutamic acid and rise
With the content of AD rat cerebral cortex inhibitory aminoacid and γ-aminobutyric acid can be increased.
5th, the rise of aurantiamarin and/or aurantiin to β-AP in experimental AD rat brains tissue has obvious suppression to make
With.
6th, aurantiamarin and/or aurantiin decline to learning and memory function caused by cerebral ischemia is significantly improved.
7th, further, mass ratio 1:9-9:1 aurantiamarin and aurantiin mixture is shown more in aspects above
Significant technique effect.
Embodiment
Embodiment 1：The preparation of aurantiamarin and/or aurantiin
Dried immature fruit of citron orange fine powder 600g, 3 (crude drugs: weight of solvent ratio is 1 are extracted with 70% ethanol：8；1：6；1：6) extraction, is merged
Liquid, recovery ethanol use petroleum ether, ethyl acetate and extracting n-butyl alcohol successively to without alcohol taste, addition distilled water to 600ml, aqueous,
Each 300ml.82g, upper D101 types macroporous resin column, successively with water, 25% second are obtained after the concentrated drying in extracting n-butyl alcohol position
Alcohol, 50% ethanol and 95% ethanol elution, more than 20% aurantiamarin and shaddock are obtained after the concentrated drying of 50% alcohol elution
The total glycosides of mixing (47g) of skin glycosides is pure through the isolated aurantiamarin of silica gel column chromatography (95%, 20g) and aurantiin (95%, 15g)
Product.Through respectively compared with IR, UV, NMR, m.p. and TLC of aurantiamarin and aurantiin standard items, it is determined that the change of two sterlings above
Learn structure.
Embodiment 2：The preparation of aurantiamarin and aurantiin mixture
The gained aurantiamarin (2g) of embodiment 1 and aurantiin (18g) are sufficiently mixed with 1: 9 ratio, stirs, grind to obtain orange peel
The mixture of glycosides and aurantiin (20g).
Embodiment 3：The preparation of aurantiamarin and aurantiin mixture
The gained aurantiamarin (10g) of embodiment 1 and aurantiin (10g) are sufficiently mixed with 1: 1 ratio, stirs, grind orange
The mixture of skin glycosides and aurantiin (20g).
Embodiment 4：The preparation of aurantiamarin and aurantiin mixture
The gained aurantiamarin (18g) of embodiment 1 and aurantiin (2g) are sufficiently mixed with 9: 1 ratios, stirs, grind to obtain orange peel
The mixture of glycosides and aurantiin (20g).
Embodiment 5：The experimental study of aurantiamarin and/or aurantiin to experimental AD preventive and therapeutic effect
1. experiment material
1.1 experimental animal：SD rats, 160~200g of body weight, male and female are regardless of, cleaning grade, by unming Medical College experimental animal
Center provides.
1.2 medicines and reagent：Crushed before 1 gained aurantiamarin and/or the experiment of aurantiin sterling will be implemented, cross 100 mesh sieves, it is molten
In water recently distilled, be made into concentration be 5% the aqueous solution be stored in it is standby in 4 DEG C of refrigerators；D- galactolipins, AMRSCO companies point
Dress；Goose cream Tan propylhomoserin (Ibotenic acid, abbreviation IBO), the purchase of Sigma companies；Huperzine-A Tablets, Tests for Uniformity (double benefits are flat), 50 μ g/ pieces,
It is purchased from ShangHai Fudan Fuhua Pharmaceutical Co., Ltd.
1.3 laboratory apparatus：Rat stands position indicator, SN-2 types, Japan's production；Dentistry drill carriage, 307-6 types, Shanghai medical analytical
Instrument plant；Agilent1100 series HPLC instrument, Agilent companies of the U.S..High speed freezing centrifuge, Shanghai medical analytical instrument
Factory；LS-6500 type liquid scintillation counters, Beckmen companies of the U.S..Keep away camera bellows：Self-control, case long 60cm, wide 25cm are high
30cm, clearly demarcated dark two Room, there is the circular hole of an a diameter of 8cm sizes between two Room.Room bottom is evenly equipped with copper grid, and the copper grid in darkroom can lead to
Electricity, from 40V voltages.Bulb equipped with 2 25W above bright room.Morris water mazes (Morris Water maze, referred to as
MWM), it is a stainless steel round pool, diameter 200cm, high 50cm, depth of water 30cm, water temperature control is in (26 ± 1) DEG C.Pool wall mark
Bright 4 place of entry, are thus divided into 4 quadrants by pond, represent platform quadrant respectively with P, O, R, L, relative to platform quadrant
Offside quadrant, right hand quadrant and left hand quadrant, center place a diameter 11cm, high 29cm platform.
Experimental data is handled with SPSS11.5 statistical packages.
2. experimental method and result
2.1 aurantiamarins and/or aurantiin hinder improved influence (Morris water to senile dementia animal model spatial cognition
Labyrinth Behaviors survey)
Thing Alzheimer-like Disease Model is activated using IBO, (Xu Shuyun etc. is edited modeling method, and pharmacology is real with reference to relevant document
The proved recipe science of law, the third edition, People's Health Publisher).After model is built up, surviving animals are randomly divided into 7 groups：1. operating comparison
Group；2. model control group；3. huperzine group；4. the gained aurantiamarin 100mg dosage groups of embodiment 1 are (equivalent to clinical agent of being grown up
The half of amount)；5. the gained aurantiin 100mg dosage groups of embodiment 1 (equivalent to the half of adult's clinical dosage)；6. embodiment 2
Gained mixture 100mg dosage groups (equivalent to the half of adult's clinical dosage)；7. the gained mixture 200mg dosage of embodiment 3
Group (equivalent to the dose,equivalent of adult's clinical dosage).Each group continuous gavage 2 months.Hereafter Morris water maze behaviouristics is carried out
Experiment, continuous 6 days, experiment was divided into two stages：(1) 1~5 day trained rat；Carry out relevant Behaviors survey within (2) the 6th days, tie
Fruit see the table below.
Table 1：The influence (x ± s) that aurantiamarin and/or aurantiin improve to senile dementia animal model spatial cognition obstacle
Note：Compared with model group, * p ＜ 0.05, * * p ＜ 0.01
As a result show, aurantiamarin and/or aurantiin improve significantly to the spatial cognition obstacle of AD rats, especially
It is the effect that embodiment 2,3 mixture groups have more conspicuousness compared with model group.
The measure of SOD, MDA activity in 2.2 serum
After water maze test is completed, after chloral hydrate anesthesia, chest is quickly opened, in Culling heart blood, 3500r/min centrifugations
Serum is taken after 10min, puts -70 DEG C of low-temperature preservations.By kit specification, tested using Ultraviolet Spectrophotometric Determination each group
SOD, MDA activity in rat blood serum.
Table 2：Aurantiamarin and/or aurantiin are to SOD, MDA activity influence tables of data in experimental rat serum
| Group | Dosage/mg.kg-1 | SOD vigor/U.ml-1 | MDA/nmol.ml |
| Operative control group | -- | 96.70±3.38 | 9.40±1.32 |
| Model group | -- | 60.20±2.35## | 21.88±3.86## |
| Huperzine group | 2×10-5 | 88.91±3.15** | 13.45±2.25** |
| The gained aurantiamarin of embodiment 1 | 100 | 94.10±3.62* | 13.16±3.81* |
| The gained aurantiin of embodiment 1 | 100 | 93.92±3.16* | 13.44±3.29* |
| The mixture of embodiment 2 | 100 | 100.16±3.58** | 12.45±3.57* |
| The mixture of embodiment 3 | 200 | 108.5±4.28** | 10.22±3.45** |
Note：Compared with model group, * p ＜ 0.05, * * p ＜ 0.01；Compared with control group, #p ＜ 0.05, ##p ＜ 0.01.
Test result indicates that being contrasted with model group, aurantiamarin and/or aurantiin can significantly improve brain tissue SOD work
Property, while MDA activity is reduced, the mixture (embodiment 2,3) of wherein aurantiamarin and aurantiin shows significantly more beneficial
Technique effect.
The influence that 2.3 aurantiamarins and/or aurantiin improve to senile dementia animal memory dysfunction
Experimental method：By above-mentioned experimental animal after administration 2 months, first experiment is placed in rat and kept away in camera bellows camera-lucida,
After rat enters camera bellows, shock by electricity 1 second, then take out animal, repeat to test after 1 week, record rat enters camera bellows by camera-lucida
Time and number, number, experimental result such as following table.
Table 3：The influence (x ± s) that aurantiamarin and/or aurantiin improve to senile dementia animal memory dysfunction
Note：Compared with model group, * p ＜ 0.05, * * p ＜ 0.01
As a result show, aurantiamarin or/and aurantiin improve significantly to the memory dysfunction of AD rats, orange peel
Glycosides and aurantiin mixture dosage group more more have significant difference with model group；Positive drug huperzine also has certain work
With.
2.4 aurantiamarins and/or aurantiin are homogenized amino acid neurotransmitter to senile dementia rat cerebral cortex tissue
Influence
After experiment 2.3 terminates, rat cerebral cortex ultrasound homogenate is taken, amino acid neurotransmitter is determined with HPLC methods
Influence.
Table 4：Aurantiamarin and/or aurantiin are homogenized amino acid neurotransmitter to senile dementia rat cerebral cortex tissue
Influence (x ± s)
Note：Compared with model group, * p ＜ 0.05, * * p ＜ 0.01；Compared with huperzine group, #p ＜ 0.05, ##p ＜
0.01。
As a result show, aurantiamarin and/or aurantiin have obvious suppression to the rise of experimental AD rat cerebral cortex glutamic acid
Make and use, the content of AD rat cerebral cortex inhibitory aminoacid and γ-aminobutyric acid can be increased, more had with model group aobvious
Write difference.Wherein aurantiamarin and aurantiin mixture (embodiment 2,3) are more notable.
2.5 aurantiamarins and/or aurantiin are to senile dementia rat brain hippocampal homogenates 4 amyloid (β-AP)
Influence
After experiment terminates, the ultrasound homogenate of rat brain hippocampus is taken, it is as a result as follows with ria-determination β-AP content.
Table 5：Aurantiamarin and/or aurantiin are to senile dementia rat brain hippocampal homogenates 4 amyloid (β-AP)
Influence (x ± s)
| Group | Mouse number | Dosage (mg/kg) | Β-AP(pg/ml) |
| Operative control group | 8 | / | 41.75±16.60** |
| Model group | 9 | / | 66.65±12.45 |
| Huperzine group | 8 | 2×10-5 | 56.89±15.49 |
| The gained aurantiamarin of embodiment 1 | 8 | 100 | 52.25±13.10* |
| The gained aurantiin of embodiment 1 | 8 | 100 | 53.46±14.32 |
| The mixture of embodiment 2 | 8 | 100 | 51.21±11.45* |
| The mixture of embodiment 3 | 8 | 200 | 47.20±5.28** |
Note：Compared with model group, * p ＜ 0.05, * * p ＜ 0.01.
As a result show, aurantiamarin and/or aurantiin 100,200mg dosage groups are to β-AP in experimental AD rat brains tissue
Rise have obvious inhibitory action, relatively have significant difference with model group.
Embodiment 6：The influence of aurantiamarin and/or aurantiin NaNO2 induced mice memory disorders
1. experiment material
1.1 experimental animal：ICR mouse, body weight 18-20g, cleaning grade, Kunming pharmacy group Experimental Animal Center.
1.2 medicines and reagent：Aurantiamarin and/or aurantiin, Jiangxi QingFeng Pharmacy Co., Ltd provide, real with embodiment 1
Test preceding crushing, cross 100 mesh sieves, be dissolved in water recently distilled, be made into the aqueous solution that concentration is 5% be stored in it is standby in 4 DEG C of refrigerators；
Jenner's multi-disc, composition containing ginkgo leaf extract 40mg/ pieces, production company of Dr Willmar Schwabe.
2. method and result
Kunming mouse 70,7 groups are randomly divided into, each group gastric infusion is after 7 days, and each group is stood after training in addition to normal group
NaNO2120mg/kg, each group 24 hours last doses after training, and the carry out diving tower examination in 1 hour after administration is subcutaneously injected
Test, it is the incubation period and errors number that record animal is made mistakes, as a result as follows.
Table 6：The influence (x ± s) of aurantiamarin and/or aurantiin NaNO2 induced mice memory disorders
Note：Compared with model group, * p ＜ 0.05, * * p ＜ 0.01.
As a result show, aurantiamarin and/or aurantiin 100,200,300mg dosage groups are to NaNO2 induced mice memory disorders
Improve significantly, the number that mouse is made mistakes can be significantly reduced, extend the incubation period that mouse is made mistakes.
Embodiment 7：The shadow of aurantiamarin and/or aurantiin to experimental blood vessel nature feeble-mindedness (VD) learning and memory function
Ring
1. experiment material
1.1 experimental animal：Male Wistar rat, body weight 450-550g, cleaning grade, by unming Medical College experimental animal
The heart provides.
1.2 medicines and reagent：Aurantiamarin and/or aurantiin, Jiangxi QingFeng Pharmacy Co., Ltd provide, real with embodiment 1
Test preceding crushing, cross 100 mesh sieves, be dissolved in water recently distilled, be made into the aqueous solution that concentration is 5% be stored in it is standby in 4 DEG C of refrigerators；
Jenner's multi-disc, composition containing ginkgo leaf extract 40mg/ pieces, production company of Dr Willmar Schwabe.
1.3 laboratory apparatus：Keep away camera bellows：Make by oneself, case long 60cm, wide 25cm, high 30cm, clearly demarcated dark two Room, have one between two Room
The circular hole of a diameter of 8cm sizes.Room bottom is evenly equipped with copper grid, and the copper grid in darkroom can be powered, from 40V voltages.Filled above bright room
There is 2 25W bulb.
Experimental data is handled with SPSS11.5 statistical packages.
2. method and result
Male Wistar rat, it is placed in and keeps away in camera bellows camera-lucida, after rat enters camera bellows, shocks by electricity 1 second, then take out dynamic
Thing.Secondary daily 10% chloraldurate (0.3ml/100g) body weight intraperitoneal anesthesia, is fixed on surgical plate, prior to overhead opening,
Exposure atlas transverse process wing aperture, burns bilateral vertebral artery with electric iron, causes permanent occlusion, skin suture.Climb over big
Mouse, exposure and free bilateral common carotid arteries, bilateral common carotid arteries are closed 5 minutes with arteriole folder folder, Reperfu- sion 1 hour, repeatedly 3
It is secondary, Ischemia Reperfusion, cause serious learning memory disorder, postoperative suture muscle, skin, 2 days anti-infective (Zhu Yu of intramuscular injection penicillin
Chief editor, the disease model of experimental animal, Tianjin Scientific English Translation publishing house).Experiment is randomly divided into 7 groups with 56 rats：1. perform the operation
Control group；2. model control group；3. Ginkgo Leaf Agent control group；4. aurantiamarin 100mg dosage groups are (equivalent to the one of adult's clinical dosage
Half)；5. aurantiin 100mg dosage groups (equivalent to the half of adult's clinical dosage)；6. the gained mixture 100mg agent of embodiment 2
Amount group (equivalent to the half of adult's clinical dosage)；7. the gained mixture 200mg dosage groups of embodiment 3 are (clinical equivalent to adult
Dose,equivalent), every group 8.Second day after operation starts medication, successive administration 10 days, will be big 1 hour after last time administration
Mouse, which is sequentially placed into, keeps away in camera bellows camera-lucida, one every time, and record enters number, number of elements and the incubation period of camera bellows in 5 minutes, as a result such as
Under.
Table 7：The influence (x ± s) that aurantiamarin and/or aurantiin improve to vascular dementia rats memory dysfunction
Note：Compared with model group, * p ＜ 0.05, * * p ＜ 0.01, SPNS are aurantiamarin and/or aurantiin.
As a result show, aurantiamarin and/or aurantiin decline the work that has clear improvement to learning and memory function caused by cerebral ischemia
With.
Pass through above-mentioned experiment, it was demonstrated that aurantiamarin and/or aurantiin are to space caused by senile dementia and cerebral ischemia
Cognitive disorder and learning and memory function decline the effect that improves significantly.Aurantiamarin and/or aurantiin can significantly improve experiment
Rat cerebral tissue SOD activity, while MDA activity is reduced, senile dementia rat cerebral cortex inhibitory aminoacid, sweet can be increased
The content of propylhomoserin and γ-aminobutyric acid, reduces the toxicity of excitability glutamic acid, and can reduce β-AP in AD Rat hippocampus
Produce, learning and memory function caused by cerebral ischemia is declined and is obviously improved effect；It can also be obviously improved small caused by NaNO2
Mouse memory disorders.
Claims (10)
1. aurantiamarin and/or aurantiin are preparing the application in improving cognition dysfunction medicine.
2. application according to claim 1, it is characterised in that the cognition dysfunction is senile dementia.
3. application according to claim 2, it is characterised in that the senile dementia is Alzheimer's disease.
4. application according to claim 2, it is characterised in that the senile dementia is cerebrovascular dementia.
5. application according to claim 1, it is characterised in that the aurantiamarin and/or aurantiin be from contain aurantiamarin
And/or extract and obtain in the medicinal material of aurantiin.
6. application according to claim 5, it is characterised in that the medicinal material containing aurantiamarin and/or aurantiin is selected from
The dried immature fruit of citron orange, Fructus Aurantii, citrus, lemon, grape fruit, Exocarpium Citri Rubrum, orange.
7. according to the application described in claim any one of 1-6, it is characterised in that the aurantiamarin and aurantiin, mass ratio
For 1:9-9:1.
8. a kind of pharmaceutical composition, include aurantiamarin and/or aurantiin and at least one pharmaceutical carrier.
9. a kind of oral formulations, include the pharmaceutical composition described in aurantiamarin and/or aurantiin or claim 8.
10. oral formulations according to claim 8, drug dose be 20-500mg/ people/time.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110693026A (en) * | 2019-04-22 | 2020-01-17 | 温州医科大学附属第一医院 | Fruit component composition for improving memory and application thereof |
| CN111759855A (en) * | 2020-08-06 | 2020-10-13 | 黑龙江中医药大学 | Traditional Chinese medicine composition for preventing and treating Alzheimer's disease and application thereof |
| CN113229499A (en) * | 2021-05-28 | 2021-08-10 | 中国人民解放军海军军医大学 | Nutritional supplement for improving mental performance in high temperature environment |
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2017
- 2017-09-03 CN CN201710782956.5A patent/CN107693530A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110693026A (en) * | 2019-04-22 | 2020-01-17 | 温州医科大学附属第一医院 | Fruit component composition for improving memory and application thereof |
| CN110693026B (en) * | 2019-04-22 | 2023-02-17 | 温州医科大学附属第一医院 | Fruit component composition for improving memory and application thereof |
| CN111759855A (en) * | 2020-08-06 | 2020-10-13 | 黑龙江中医药大学 | Traditional Chinese medicine composition for preventing and treating Alzheimer's disease and application thereof |
| CN113229499A (en) * | 2021-05-28 | 2021-08-10 | 中国人民解放军海军军医大学 | Nutritional supplement for improving mental performance in high temperature environment |
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