CN106581335A - Medicine composition for treating Alzheimer's disease and preparing method and application thereof - Google Patents
Medicine composition for treating Alzheimer's disease and preparing method and application thereof Download PDFInfo
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- CN106581335A CN106581335A CN201710011015.1A CN201710011015A CN106581335A CN 106581335 A CN106581335 A CN 106581335A CN 201710011015 A CN201710011015 A CN 201710011015A CN 106581335 A CN106581335 A CN 106581335A
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- 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
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- 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)
- A61K36/69—Polygalaceae (Milkwort family)
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
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Abstract
The invention discloses a medicine composition for treating Alzheimer's disease and a preparing method and application thereof. The active constituents of the medicine composition are composed of, by weight, 8-30 parts of total saponins in polygalaceae and 1-5 parts of acorustatatinowii schott naphtha. The medicine composition for treating Alzheimer's disease can effectively treat Alzheimer's disease.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition, in particular for treating the pharmaceutical composition of senile dementia, further relates to
The preparation method and purposes of said composition.
Background technology
Senile dementia, also known as Alzheimer (Alzheimer disease, AD), is a kind of central nervous system
Degenerative disease, insidious onset, in chronic progressive external, senile dementia is mainly shown as gradual memory obstacle, cognitive function to the course of disease
The neuropsychic symptoms such as obstacle, personality changeies and aphasis, have a strong impact on social activity, occupation and vital function.Senile dementia
The cause of disease and pathogenesis not yet illustrate, treatment there is no specific short, based on symptomatic treatment, improve cognitive including Drug therapy
Function and dysmnesia, symptomatic treatment improve mental symptom, good nursing and delay disease progression.In medicine, cholinester
Enzyme inhibitor and this two classes medicine of glutamate receptor antagonists are the most commonly used, its for the clinical symptoms of patient are improved in terms of have
Certain effect, but there is also many untoward reaction.For example, cholinesterase inhibitor donepezil can cause the symptoms such as nausea, diarrhoea,
Even some patients occur easily enraging, the abalienation phenomenon such as aggressive behavior；The glutamate receptor for the treatment of severe Alzheimer's disease
The untoward reaction such as body antagonist " memantine " causes patient to hallucinate, misunderstanding, dizziness, headache.These untoward reaction and use
Medicine risk limits their Clinical practice to a certain extent.
Existing plurality of Chinese and natural drug are also used for treating senile dementia, also including some Chinese medicine extract or from
The monomer component extracted in Chinese medicine or compositionss.Chinese patent application CN201210109961.7 discloses one kind and treats A Erci
The compound Chinese medicinal preparation of extra large Mo's disease, is made up of Radix Angelicae Sinensis, Rhizoma Acori Graminei, Radix Rehmanniae, Rhizoma Chuanxiong, Herba Epimedii, Fructus Mori, Radix Polygalae.It is Chinese special
Profit application CN201410140646.X discloses a kind of Chinese medicine with treatment Alzheimer, by the raw material of following weight portion
Medicine is made：Radix Morindae Officinaliss 5～20,5～20 parts of Rhizoma Acori Graminei, 5～30 parts of Radix Curcumae, 5～30 parts of the Radix Astragali, 1～20 part of Radix Polygalae.Chinese patent
Application CN201410693128.0 discloses a kind of Compound Chinese Herbal Monomer Recipe compositionss of preventing and treating Alzheimer, including ligustrazine
2 parts of 3 parts, 2 parts of polygalic acid and stilbene glucoside.These Drug therapy Alzheimer are respectively provided with certain curative effect.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition for treating senile dementia, pharmaceutical composition treatment
Effect is definite, with low cost.
Another object of the present invention is to provide the preparation method of described pharmaceutical composition.
It is still another object of the present invention to provide the preparation for treating senile dementia.
A further object of the present invention is the purposes of the pharmaceutical composition for providing described.
The purpose of the present invention is achieved by the following technical solution：
The present invention provides a kind of pharmaceutical composition for treating senile dementia, and its active component is by Radix Polygalae total saponins 8～30
Weight portion and 1～5 weight portion of Rhizoma Acori Graminei volatile oil composition.
Pharmaceutical composition of the invention, it is preferable that the Pharmaceutical ingredients of described pharmaceutical composition by Radix Polygalae total saponins 8～
20 weight portions and 1～2 weight portion of Rhizoma Acori Graminei volatile oil composition.
Pharmaceutical composition of the invention, it is preferable that the Pharmaceutical ingredients of described pharmaceutical composition by Radix Polygalae total saponins 8～
12 weight portions and 1 weight portion of Rhizoma Acori Graminei volatile oil composition.
Pharmaceutical composition of the invention, it is preferable that the Pharmaceutical ingredients of described pharmaceutical composition are weighed by Radix Polygalae total saponins 8
Amount part and 1 weight portion of Rhizoma Acori Graminei volatile oil composition.
Pharmaceutical composition of the invention, it is preferable that the Pharmaceutical ingredients of described pharmaceutical composition are by Radix Polygalae total saponins 10
Weight portion and 1 weight portion of Rhizoma Acori Graminei volatile oil composition.
Pharmaceutical composition of the invention, it is preferable that the Pharmaceutical ingredients of described pharmaceutical composition are by Radix Polygalae total saponins 12
Weight portion and 1 weight portion of Rhizoma Acori Graminei volatile oil composition.
Pharmaceutical composition of the invention, it is preferable that in described Radix Polygalae total saponins the content of tenuifolin is not
Less than 15wt%.
In the present invention, described Radix Polygalae total saponins are prepared via a method which to obtain：
(1) Radix Polygalae is carried out into supercritical extraction, removes supercritical extract, then it is water-soluble using the ethanol of 50～80vol%
Liquid is extracted as solvent, obtains extracting solution；
(2) extracting solution is made into loading sample, by macroporous resin column on the loading sample, uses the first eluting successively
Agent, the second eluant and the 3rd eluting eluant carry out eluting, obtain the first eluent, the second eluent and the 3rd eluting successively
Liquid, collects the 3rd eluent；The first described eluant is water, and the second eluant is the ethanol water of 15～25vol%, the
Three eluant are the ethanol water of 55～80vol%；
(3) the 3rd eluent is concentrated, is dried, obtains the Radix Polygalae total saponins.
In the present invention, Radix Polygalae is carried out supercritical extraction process by step (1) first, removes supercritical extract, so as to remove
The low polarity component gone in Radix Polygalae.Inventor has found, removes the low polarity volatile oil component in Radix Polygalae first, be conducive to subsequently washing
Highly purified Radix Polygalae total saponins are obtained in de- program.
In the present invention, extracted with solvent after Radix Polygalae is removed volatile oil component in step (1).Preferably, it is described molten
Agent is the ethanol water of 55～75vol%, more preferably the ethanol water of 65～75vol%, further preferably for 70～
The ethanol water of 75vol%.
In the present invention, the extracting method of the Radix Polygalae of step (1) is selected from heating reflux method, ultrasonic method, infusion process or percolation.
Preferably, the extracting method of described Radix Polygalae is heating reflux method.An embodiment of the invention, in step (1), will
Radix Polygalae using the ethanol water of 55～75vol% as solvent extraction 1～4 time, each solvent load for Radix Polygalae weight 5～
12 times, each extraction time is 1～4 hour, obtains described extracting solution.One of the invention is preferred embodiment,
In step (1), adopt the ethanol water of 70vol% as solvent extraction 3 times Radix Polygalae, each solvent load is followed successively by Radix Polygalae
8 times, 6 times, 6 times of weight, each extraction time is 1 hour, obtains described extracting solution.
In the present invention, it is preferable that the resin described in step (2) is D101 macroporous resins.
In the present invention, it is preferable that the method that extracting solution is made loading sample described in step (2) is：Will be described
Extracting solution reclaim ethanol after add water adjust to equivalent to per milliliter containing Polygala tenuifolia weight be 0.1～1.0g, preferably 0.1～
The solution of 0.5g, more preferably 0.1～0.3g, as loading sample.
In the present invention, it is preferable that in step (2), the second eluant is the ethanol water of 15～25vol%, more preferably
For the ethanol water of 18～22vol%.3rd eluant is the ethanol water of 55～80vol%, more preferably 60～
The ethanol water of 75vol%.
In the present invention, it is preferable that in step (2), the consumption of the first eluant is 2～7 times of column volume, the second eluant
Consumption be 4～8 times of column volume, 4～8 times for column volume of the consumption of the 3rd eluant.It is highly preferred that the first eluant
4～6 times for column volume of consumption, the consumption of the second eluant are 5～7 times of column volume, and the consumption of the 3rd eluant is cylinder
Long-pending 5～7 times.
In the present invention, it is preferable that in step (2), the eluting of first eluant, the second eluant and the 3rd eluant
Speed is 0.1～1.0ml/min, more preferably 0.1～0.5ml/min.It is according to one preferred embodiment of the invention, described
The elution speed of the first eluant, the second eluant and the 3rd eluant is 0.25ml/min.
The method for preparing Radix Polygalae total saponins of the present invention, carries out supercritical extraction process first, removes the low pole in Radix Polygalae
Property composition, then Jing ethanol solution extract, it is by extracting solution by above-mentioned macroporous resin remove impurity, miscellaneous in Radix Polygalae so as to effectively remove
Matter composition, obtains being enriched with the eluent of polygalic acid constituents.
Pharmaceutical composition of the invention, it is preferable that the content of beta-Asarone is not low in described Rhizoma Acori Graminei volatile oil
3wt% is not less than in the content of 50wt%, α-asaricin.
In the present invention, described Rhizoma Acori Graminei volatile oil is by adopting steam distillation or super critical extraction by Rhizoma Acori Graminei
Prepare.
An embodiment of the invention, the preparation method of Rhizoma Acori Graminei volatile oil is：Rhizoma Acori Graminei plus 6～15 times of amounts
Water, extraction by steam distillation 3～8 hours collect Rhizoma Acori Graminei volatile oil.An embodiment of the invention, it is described
The preparation method of Rhizoma Acori Graminei volatile oil is：Rhizoma Acori Graminei plus 12 times of amount water, extraction by steam distillation 5 hours are collected into Rhizoma Acori Graminei
Volatile oil.
According to another implementation of the invention, the preparation method of Rhizoma Acori Graminei volatile oil is：Rhizoma Acori Graminei is placed in into super facing
In boundary's carbon dioxide abstraction instrument, extraction temperature is 45～65 DEG C, preferably 50～60 DEG C, more preferably 55～60 DEG C；Extraction pressure
Power is 20～40MPa, more preferably 25～35MPa；Extraction time be 60～120min, preferably 70～100min, more preferably
For 80～95min；Collect extract.An embodiment of the invention, the preparation method of Rhizoma Acori Graminei volatile oil is by stone
Rhizoma Acori Graminei is placed in supercritical carbon dioxide extraction instrument, and extraction temperature is 59 DEG C, and extracting pressure is 28MPa, and extraction time is
90min。
The present invention also provides the preparation method of described pharmaceutical composition, including described Radix Polygalae total saponins and Rhizoma Acori Graminei are waved
Hair oil mix homogeneously.Preferably, described Rhizoma Acori Graminei volatile oil after beta-cyclodextrin inclusion compound again with described Radix Polygalae total saponins
Mix homogeneously.
The preparation method of pharmaceutical composition of the invention, it is preferable which comprises the steps：
1) preparation process of Radix Polygalae total saponins：
(1) Radix Polygalae is carried out into supercritical extraction, removes supercritical extract, then it is water-soluble using the ethanol of 50～80vol%
Liquid is extracted as solvent, obtains extracting solution；
(2) extracting solution is made into loading sample, by macroporous resin column on the loading sample, uses the first eluting successively
Agent, the second eluant and the 3rd eluting eluant carry out eluting, obtain the first eluent, the second eluent and the 3rd eluting successively
Liquid, collects the 3rd eluent；The first described eluant is water, and the second eluant is the ethanol water of 15～25vol%, the
Three eluant are the ethanol water of 55～80vol%；
(3) the 3rd eluent is concentrated, is dried, obtains the Radix Polygalae total saponins；
2) preparation process of Rhizoma Acori Graminei volatile oil：
Rhizoma Acori Graminei is placed in supercritical carbon dioxide extraction instrument, extraction temperature be 45～65 DEG C, extracting pressure be 20～
40MPa, extraction time are 60～120min, obtain described Rhizoma Acori Graminei volatile oil；
3) blend step：
By step 2) Rhizoma Acori Graminei volatile oil that obtains through beta-cyclodextrin inclusion compound, then with step 1) Radix Polygalae total saponins that obtain
Mix homogeneously.
Technological parameter in above-mentioned steps is as it was previously stated, repeat no more here.
The present invention also provides a kind of pharmaceutical preparation for treating senile dementia, and described pharmaceutical preparation includes above-mentioned medicine
Compositionss, and pharmaceutically acceptable adjuvant.The pharmaceutically acceptable adjuvant includes but is not limited to starch, dextrin, sucrose,
Microcrystalline Cellulose, Lactose, Macrogol 4000, polyethylene glycol 6000, vegetable oil, Cera Flava etc..The dosage form of described pharmaceutical preparation
Selected from soft capsule, hard capsule, drop pill, tablet, granule etc..
The present invention also provides described pharmaceutical composition to be used to prepare the medicine or health food for the treatment of senile dementia
Purposes.
The Radix Polygalae total saponins of the consumption proportion of the present invention and the pharmaceutical composition of Rhizoma Acori Graminei volatile oil composition, are crazy about for old
Slow-witted disease (i.e. Alzheimer) is with obvious therapeutic effect.
Specific embodiment
With reference to specific embodiment, the present invention is further illustrated, but protection scope of the present invention is not limited to
This.
In the present invention, described senile dementia is Alzheimer (Alzheimer disease, AD).
In the present invention, described Radix Polygalae is that milk wort Radix Polygalae Polygala tenuifolia Willd. or ovum leaf are remote
The dry root of will Polygala sibirica L..Described Rhizoma Acori Graminei is acorus gramineus araceae plant Acorus
The dry rhizome of tatarinowii Schott.
Preparation example 1
The preparation of Radix Polygalae total saponins：Polygala tenuifolia 5kg is taken, the coarse granule of 20 mesh is ground into, supercritical carbon dioxide is carried out
Extraction process, after removing supercritical extract, adds 70vol% ethanol solution as solvent extraction 3 times, and solvent load is followed successively by
8 times of amounts of Polygala tenuifolia weight, 6 times of amounts, 6 times of amounts, extract 1 hour every time, filter, and merging filtrate obtains extracting solution；By gained
Extracting solution rotary evaporation reclaims ethanol to remaining 5000ml, and cold preservation 12 hours separates upper strata, discards, and lower floor's aqueous add water adjustment
To 25L, by D101 macroporous resin column, (blade diameter length ratio is 1:8), respectively with the water (the first eluant) of 5 times of column volumes, 5 times of cylinders
Long-pending 25vol% ethanol waters (the second eluant), the 70vol% ethanol waters (the 3rd eluant) of 5 times of column volumes are washed
It is de-, collect the eluent that 70vol% ethanol water eluting is obtained.The eluent is reclaimed into ethanol, is dried, is obtained the total soap of Radix Polygalae
Glycosides.Jing is determined, and in the Radix Polygalae total saponins, the content of tenuifolin is 18.6wt%.
Preparation example 2
The preparation of Radix Polygalae total saponins：Polygala tenuifolia 10kg is taken, the coarse granule of 20 mesh is ground into, supercritical carbon dioxide is carried out
Extraction process, after removing supercritical extract, adds 80vol% ethanol as solvent extraction 2 times, and each solvent load is Radix Polygalae
6 times of amounts of weight, extract 0.5 hour every time, filter, and merging filtrate obtains extracting solution；Gained extracting solution rotary evaporation is reclaimed
Ethanol separates upper strata, discards to remaining 8L, cold preservation 12 hours, and lower floor's aqueous add water and adjust to 80L, by D101 macroporous resins
(blade diameter length ratio is 1 to post:6), respectively with 5 times amount wet resin volumes water (the first eluant), 7 times amount 20vol% ethanol it is water-soluble
Liquid (the second eluant), 75vol% ethanol waters (the 3rd eluant) eluting of 6 times of column volumes collect 75vol% ethanol waters
The eluent that eluant solution is obtained.The eluent is reclaimed into ethanol, is dried, is obtained Radix Polygalae total saponins.Jing is determined, the total soap of the Radix Polygalae
In glycosides, the content of tenuifolin is 16.8wt%.
Preparation example 3
The preparation of Rhizoma Acori Graminei volatile oil：Rhizoma Acori Graminei medical material is taken, the coarse granule of 20 mesh sieves, plus 12 times of amount water, water was ground into
Steam distillation method extracts volatile oil 5 hours, collects volatile oil, obtains Rhizoma Acori Graminei volatile oil.Jing is determined, and β in Rhizoma Acori Graminei volatile oil-
The content of asaricin is 4.8wt% for the content of 55.2wt%, α-asaricin.
Preparation example 4
The preparation of Rhizoma Acori Graminei volatile oil：Rhizoma Acori Graminei medical material is taken, the coarse powder of 40 mesh sieves was ground into, supercritical titanium dioxide is placed in
The extraction kettle of carbon abstraction instrument, 59 DEG C of extraction temperature, extracting pressure 28mPa, extraction time 90min are collected extract, obtain stone Chang
Pu volatile oil.Jing is determined, and in Rhizoma Acori Graminei volatile oil, the content of beta-Asarone for the content of 58.1wt%, α-asaricin is
5.2wt%.
Embodiment 1
The preparation of pharmaceutical composition：By Rhizoma Acori Graminei volatile oil 100g obtained in 3 method of preparation example, beta-schardinger dextrin -400g is added
Inclusion, obtains 500g clathrates.
By the Radix Polygalae total saponins 40g of preparation example 1 and the clathrate 25g, mix homogeneously, the medicine group of the present embodiment is obtained
Compound.
Embodiment 2
The preparation of pharmaceutical composition：Rhizoma Acori Graminei volatile oil 100g obtained in 4 method of preparation example is taken, beta-schardinger dextrin-is added
1200g is included, and obtains 1300g clathrates.By Radix Polygalae total saponins 100g obtained in 2 method of the preparation example and clathrate 130g,
Multidimensionblender mix homogeneously is added, the pharmaceutical composition of the present embodiment is obtained.
Embodiment 3
The preparation of pharmaceutical composition：Rhizoma Acori Graminei volatile oil 10g obtained in 3 method of preparation example is uniformly sprayed at into preparation example 2
In Radix Polygalae total saponins 100g obtained in method, the pharmaceutical composition of the present embodiment is obtained.
Embodiment 4
The preparation of pharmaceutical composition：Rhizoma Acori Graminei volatile oil 20g obtained in 4 method of preparation example is uniformly sprayed at into preparation example 1
In Radix Polygalae total saponins 180g obtained in method, the pharmaceutical composition of the present embodiment is obtained.
Embodiment 5
The preparation of pharmaceutical preparation：By pharmaceutical composition 100g obtained in 1 method of embodiment, Lactose 100g is added, mixed, done
Compacting grain, obtains granule.
Embodiment 6
The preparation of pharmaceutical preparation：By pharmaceutical composition 100g obtained in embodiment 2, starch 70g is added, mixed, used
Used as wetting agent, granulation, less than 60 DEG C are dried 80vol% ethanol, and granulate, filled hard capsules obtain hard capsule.
Embodiment 7
The preparation of pharmaceutical preparation：The PEG6000 of 300g is taken, heating melting adds the total soap of Radix Polygalae obtained in 2 method of preparation example
Glycosides 120g, Rhizoma Acori Graminei volatile oil 10g obtained in 3 method of preparation example, stir, and instill in dimethicone, take out drop pill, wipe
The dimethicone on surface is removed, drop pill is obtained.
Experimental example
Therapeutical effect of the pharmaceutical composition of the present invention to senile dementia is demonstrated by the test of pesticide effectiveness.Experimental technique and
As a result it is as follows：
1. animal and material
1.1 animal：Healthy Wistar rats, SPF levels, 200～220g of body weight, 24 ± 0.5 DEG C of temperature, humidity is maintained at 60
± 2vol%, indoor light are controlled in normal circadian rhythm (bright light during morning 8), and animal freely obtains food and water.
The preparation of 1.2 senile dementia animal models (AD animal models)
Senlie dementia model adopts modeling with the following method：Rat nape part subcutaneous injection D- galactose 50mg/ (kgd),
Continuous 6 weeks, the 7th week intracerebroventricular injection A β 25-35 (Sigma Co., USA's product).Rat pentobarbital sodium (45mg/kg) is anaesthetized
Afterwards, it is fixed on brain solid positioner, head median incision, exposes bregma, with reference to rat brain stereotaxic atlas, with anterior fontanelle
For reference point, the 1.3mm after bregma, side open 2mm and will be inserted perpendicularly into 10 μ l micro-injections with 5ml injection needles one aperture of brill
Device, depth 40mm (reach at tricorn), the A β 25-35 of 5 μ l state of aggregations of slow injection, injection time continue 10min, let the acupuncture needle remain at a certain point 5min,
After injection is finished, locally spreading bactrim medicated powder prevents infection, sutures scalp, and it is single per only 50,000 that postoperative muscle injects penicillin
Position, continuous 4d obtain senile dementia rat model (simple rat model below).
1.3 animal packets and administration
Blank control group：Healthy rat 10, gives the distilled water of 5ml/kg daily.
Model control group：Rat model 11, gives the distilled water of 5ml/kg daily.
Positive controls：Rat model 11, nimodipine tablet is finely ground, and beginning in postoperative 2nd day is given according to 15mg/kg
Medicine, 1 times/day.
Compare 1 group：Rat model 10, takes the Radix Polygalae total saponins 60g of preparation example 1, is dissolved in water to 0.06g/ml；It is postoperative
2nd day starts, according to 5ml/kg gastric infusions, 1 times/day.
Compare 2 groups：Rat model 10, takes the Rhizoma Acori Graminei volatile oil 60g of preparation example 3, adds beta-cyclodextrin inclusion compound extremely
300g, the cyclodextrin volatile oil after this is included add water and are suspended to 0.06g/ml containing Rhizoma Acori Graminei volatile oil, start within postoperative 2nd day by
According to 5ml/kg gastric infusions, 1 times/day.
Of the present invention group：Rat model 10, the pharmaceutical composition 125.45g of Example 2, is dissolved in water to 0.125g/
Ml, postoperative 2nd day starts, according to 5ml/kg gastric infusions, 1 times/day.
It is administered above, after continuous 6 weeks, carries out subsequent experimental.
2. experimental technique
2.1 8 arm labyrinth behavioristicss determine
Gavage starts eight arm labyrinths on the 6th week, and radial eight arm (four arms put food) is a kind of classical measure animal
The method of spatial memory, it can detect the reference memory and working memory of animal simultaneously.Labyrinth central area diameter 30cm, Xiang Si
Week equiangularly extends eight arm with equal length.Before training, rat first adapts to 1d in labyrinth, and during adaptation, 3 to 4 rats are simultaneously
It is placed in labyrinth, freely activity and intake food 10min.The training per 1 time is carried out after adaptation.When training every time, in eight arms only
There are four arms to placed food (arm of respectively 1,3,6 and 7), whole experiment process maintains this order.Rat is placed on labyrinth central authorities
Area, now central area surrounding door bar up 15s and door opened, rat is may be selected into any one arm, to absorb food.Rat enters
Enter to have the arm of food and intake of food and correctly select for 1 time, be otherwise wrong choice.Recording parameterses are the secondary of wrong choice
Number.Reenter and put food arm referred to as working memory error (working memory error；WME), enter and do not put food arm
Referred to as reference memory mistake (reference memory error；RME).Continuous 5 training, the 6th formal detection.
Superoxide dismutase (SOD) vigor, malonaldehyde (MDA) content detection in 2.2 rat blood serums
After eight arm Y-maze tests, stop eating 12h, urethane (0.8g/kg) intraperitoneal injection of anesthesia, and back of the body position is fixed, and hits exactly along abdomen
Line cuts, and postcava takes blood, separates serum, determines SOD in serum by SOD kit specifications；Survey by MDA kit specifications
Determine serum MDA.
Acetylcholinesterase (AchE) content detection in 2.3 rat blood serums and brain
Serum is taken according to 2.2 methods, serum AchE is determined by kit specification.After taking blood, rat is put to death, and takes brain group
Knitting, removing blood film, olfactory bulb and cerebellum, rearmounted refrigerator～20 DEG C for 5min being placed with liquid nitrogen preserve, and take left hemisphere within the 2nd day, by examination
Agent box description determines cerebral tissue AchE, cerebral tissue protein determination biuret method.
2.4 statistical analysiss
Data are usedRepresent, compare between group and checked using t, P<0.05 is statistically significant.
3. experimental result
3.1 8 arm labyrinth behavioristicss determination test results
The result of the test is shown in Table 1.Compare with blank control group, rat reference memory mistake (RME) of model control group shows
Write and raise (P ＜ 0.05), working memory error (WME) has rising trend, but there was no significant difference.The present invention has been organized notable and has been reduced
Rat model reference memory mistake (RME) (P ＜ 0.05), has reduction trend to working memory error (WME).As a result show this
It is bright that rat model learning memory disorder is significantly improved, learning memory can be improved.
1 rat of table, eight arm labyrinth behavioristicss determination test result
Note：△ represented and compared with model control group, P<0.05.
3.2 SOD in serum, MDA determination test results
The result of the test is shown in Table 2.Compare with blank control group, model control group rat blood serum SOD has reduction trend, serum
MDA contents raise (P ＜ 0.05).The model mouse serum activity of SOD of present invention group significantly raises (P ＜ 0.01), model mouse serum
MDA contents significantly reduce (P ＜ 0.01).As a result show that the present composition can improve the SOD vigor in rat model serum, from
And the ability of enhancing body scavenging activated oxygen, reduce the generation of malonaldehyde.
SOD, MDA measurement result in 2 rat blood serum of table
Note：△ represented and compared with model control group, P<0.05；
△ Δs are represented and are compared with model control group, P<0.01；
▲▲Expression is compared with positive controls, P<0.01.
3.3 serum and cerebral tissue AchE determination test results
The result of the test is shown in Table 3.Compare with blank control group, in model control group rat blood serum and cerebral tissue, AchE is notable
Raise (P ＜ 0.05)；Of the present invention group can reduce AchE vigor (P ＜ 0.05) in rat model serum, significantly reduce cerebral tissue
Middle AchE vigor (P ＜ 0.01), and compare with nimodipine group and also have significant difference (P ＜ 0.05).As a result show the present invention
Compositionss can significantly reduce AchE vigor in rat model serum and cerebral tissue.
3 rat blood serum of table and brain AchE determination test results
Note：△ represented and compared with model comparison, P<0.05；
△ Δs are represented and are compared with model control group, P<0.01；
■ represented and compared with positive controls, P<0.05.
As fully visible, Chinese medicine composition of the invention can improve SOD vigor in senile dementia model mouse serum, reduce mould
MDA contents in type Mus serum, and there is improvement result to rat model learning memory disorder.Meanwhile, the present composition can also
AchE vigor in senile dementia rat cerebral tissue and serum is significantly reduced, levels of acetylcholine is improved, so as to strengthen cholinergic god
Jing systemic-functions, improve learning and memory state.As a result show, the pharmaceutical composition of the present invention has significantly to senile dementia
Therapeutical effect, and effect is better than the curative effect that Radix Polygalae total saponins and Rhizoma Acori Graminei volatile oil are individually used.
The present invention is not limited to above-mentioned embodiment, in the case of the flesh and blood without departing substantially from the present invention, this area skill
Any deformation that art personnel are contemplated that, improvement, replacement each fall within the scope of the present invention.
Claims (10)
1. a kind of pharmaceutical composition for treating senile dementia, it is characterised in that the active component in described pharmaceutical composition by
8～30 weight portion of Radix Polygalae total saponins and 1～5 weight portion of Rhizoma Acori Graminei volatile oil composition.
2. pharmaceutical composition according to claim 1, it is characterised in that the Pharmaceutical ingredients of described pharmaceutical composition are by Radix Polygalae
8～20 weight portion of total saponins and 1～2 weight portion of Rhizoma Acori Graminei volatile oil composition.
3. pharmaceutical composition according to claim 1, it is characterised in that the Pharmaceutical ingredients of described pharmaceutical composition are by as follows
Into being grouped into：
1 weight portion of 8 weight portion of Radix Polygalae total saponins and Rhizoma Acori Graminei volatile oil；Or
1 weight portion of 10 weight portion of Radix Polygalae total saponins and Rhizoma Acori Graminei volatile oil；Or
1 weight portion of 12 weight portion of Radix Polygalae total saponins and Rhizoma Acori Graminei volatile oil.
4. the pharmaceutical composition according to any one of claims 1 to 3, it is characterised in that thin in described Radix Polygalae total saponins
The content of leaf polygalic acid is not less than 15wt%.
5. the pharmaceutical composition according to any one of claims 1 to 3, it is characterised in that described Radix Polygalae total saponins pass through
Following method is prepared：
(1) Radix Polygalae is carried out into supercritical extraction, removes supercritical extract, then using the ethanol water work of 50～80vol%
Extracted for solvent, obtained extracting solution；
(2) extracting solution is made into loading sample, by macroporous resin column on the loading sample, successively with the first eluant,
Second eluant and the 3rd eluting eluant carry out eluting, obtain the first eluent, the second eluent and the 3rd eluent successively,
Collect the 3rd eluent；The first described eluant is water, and the second eluant is the ethanol water of 15～25vol%, the 3rd
Eluant is the ethanol water of 55～80vol%；
(3) the 3rd eluent is concentrated, is dried, obtains the Radix Polygalae total saponins.
6. the pharmaceutical composition according to any one of claims 1 to 3, it is characterised in that in described Rhizoma Acori Graminei volatile oil
The content of beta-Asarone is not less than the content of 50wt%, α-asaricin and is not less than 3wt%.
7. the pharmaceutical composition according to any one of claims 1 to 3, it is characterised in that described Rhizoma Acori Graminei volatile oil
Preparation method is：Rhizoma Acori Graminei is placed in supercritical carbon dioxide extraction instrument, extraction temperature is 45～65 DEG C, and extracting pressure is 20
～40MPa, extraction time are 60～120min, obtain the Rhizoma Acori Graminei volatile oil.
8. the preparation method of the pharmaceutical composition according to any one of claims 1 to 3, it is characterised in that including following step
Suddenly：
1) preparation process of Radix Polygalae total saponins：
(1) Radix Polygalae is carried out into supercritical extraction, removes supercritical extract, then using the ethanol water work of 50～80vol%
Extracted for solvent, obtained extracting solution；
(2) extracting solution is made into loading sample, by macroporous resin column on the loading sample, successively with the first eluant,
Second eluant and the 3rd eluting eluant carry out eluting, obtain the first eluent, the second eluent and the 3rd eluent successively,
Collect the 3rd eluent；The first described eluant is water, and the second eluant is the ethanol water of 15～25vol%, the 3rd
Eluant is the ethanol water of 55～80vol%；
(3) the 3rd eluent is concentrated, is dried, obtains the Radix Polygalae total saponins；
2) preparation process of Rhizoma Acori Graminei volatile oil：
Rhizoma Acori Graminei is placed in supercritical carbon dioxide extraction instrument, extraction temperature be 45～65 DEG C, extracting pressure be 20～
40MPa, extraction time are 60～120min, obtain described Rhizoma Acori Graminei volatile oil；
3) blend step：
By step 2) Rhizoma Acori Graminei volatile oil that obtains through beta-cyclodextrin inclusion compound, then with step 1) Radix Polygalae total saponins that obtain mix
Uniformly.
9. a kind of pharmaceutical preparation for treating senile dementia, comprising according to any one of claim 1～7 in described pharmaceutical preparation
Described pharmaceutical composition.
10. the pharmaceutical composition according to any one of claim 1～7 is used for medicine or the guarantor for preparing treatment senile dementia
Purposes in health food.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710011015.1A CN106581335A (en) | 2017-01-06 | 2017-01-06 | Medicine composition for treating Alzheimer's disease and preparing method and application thereof |
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| CN201710011015.1A CN106581335A (en) | 2017-01-06 | 2017-01-06 | Medicine composition for treating Alzheimer's disease and preparing method and application thereof |
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Family
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710011015.1A Pending CN106581335A (en) | 2017-01-06 | 2017-01-06 | Medicine composition for treating Alzheimer's disease and preparing method and application thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107115430A (en) * | 2017-06-21 | 2017-09-01 | 芜湖耄智生物科技有限公司 | Chinese medicine drink containing huperzine and preparation method thereof |
| CN107158299A (en) * | 2017-06-26 | 2017-09-15 | 北华大学 | It is a kind of that there is composition of enhancing learning memory function and preparation method thereof |
| CN110664919A (en) * | 2019-11-25 | 2020-01-10 | 湖北中医药大学 | Pharmaceutical composition for resisting senile dementia and preparation method and application thereof |
| CN112717031A (en) * | 2021-01-13 | 2021-04-30 | 诸城市精神卫生中心 | Pharmaceutical composition for treating Alzheimer's disease and preparation method thereof |
| CN112755074A (en) * | 2021-01-21 | 2021-05-07 | 上海普康药业有限公司 | Pharmaceutical composition containing oryzanol and preparation method and application thereof |
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| CN101444580A (en) * | 2008-12-30 | 2009-06-03 | 中国医药集团总公司四川抗菌素工业研究所 | Chinese drug composition for senile dementia prevention and cure |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101444580A (en) * | 2008-12-30 | 2009-06-03 | 中国医药集团总公司四川抗菌素工业研究所 | Chinese drug composition for senile dementia prevention and cure |
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| 张智华，王秀莲，等: "石菖蒲-远志药对不同组分对阿尔茨海默病模型大鼠海马Tau 蛋白及其Ser396位点磷酸化的影响", 《医药导报》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107115430A (en) * | 2017-06-21 | 2017-09-01 | 芜湖耄智生物科技有限公司 | Chinese medicine drink containing huperzine and preparation method thereof |
| CN107158299A (en) * | 2017-06-26 | 2017-09-15 | 北华大学 | It is a kind of that there is composition of enhancing learning memory function and preparation method thereof |
| CN107158299B (en) * | 2017-06-26 | 2020-06-09 | 北华大学 | Composition with function of enhancing learning memory and preparation method thereof |
| CN110664919A (en) * | 2019-11-25 | 2020-01-10 | 湖北中医药大学 | Pharmaceutical composition for resisting senile dementia and preparation method and application thereof |
| CN112717031A (en) * | 2021-01-13 | 2021-04-30 | 诸城市精神卫生中心 | Pharmaceutical composition for treating Alzheimer's disease and preparation method thereof |
| CN112755074A (en) * | 2021-01-21 | 2021-05-07 | 上海普康药业有限公司 | Pharmaceutical composition containing oryzanol and preparation method and application thereof |
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