CN109925402A

CN109925402A - A kind of Chinese medicine composition and the preparation method and application thereof

Info

Publication number: CN109925402A
Application number: CN201910088116.8A
Authority: CN
Inventors: 李萍; 解素花; 杨华; 肖婷婷; 李飞; 张蓓; 季晖; 候譞; 徐晓军
Original assignee: BEIJING ZHONGYAN TONGRENTANG MEDICAL DEVELOPMENT Co Ltd; China Pharmaceutical University
Current assignee: BEIJING ZHONGYAN TONGRENTANG MEDICAL DEVELOPMENT Co Ltd; China Pharmaceutical University
Priority date: 2019-01-29
Filing date: 2019-01-29
Publication date: 2019-06-25
Anticipated expiration: 2039-01-29
Also published as: CN109925402B

Abstract

The invention belongs to technical field of traditional Chinese medicine preparation, more particularly to a kind of Chinese medicine composition and the preparation method and application thereof, bulk pharmaceutical chemicals including following parts by weight: 2-15 parts of ginseng, 2-15 parts of Semen Ziziphi Spinosae (parched), 2-15 parts of Herba Epimedii Preparata, 3-18 parts of Rehmannia glutinosa, 1-12 parts of RADIX POLYGALAE PREPARATA, 1-12 parts of stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, 3-18 parts of Radix Angelicae Sinensis, 2-15 parts of rhizoma acori graminei, 1-10 parts of radix glycyrrhizae preparata, complete square compatibility 5 is rigorous, simultaneous treatment of principal and subordinate symptoms, training vigour is played altogether, tonifying five zang organs, resolving sputum promoting blood circulation, the function of brain-care, it is fed back through animal pharmacodynamic experiment and later phase clinical, traditional Chinese medicine composition for treating senile dementia produced by the present invention has target spot more, it is highly-safe, good effect, the advantage that applicability extensively waits.

Description

A kind of Chinese medicine composition and the preparation method and application thereof

Technical field

The invention belongs to technical field of traditional Chinese medicine preparation, and in particular to a kind of Chinese medicine composition and the preparation method and application thereof.

Background technique

Alzheimer disease (Alzheimerdisease, AD), also known as senile dementia, be a kind of progress sexual development and Irreversible nervous system degenerative disease.The disease mainly with memory disorders, intelelectual deterioration, execute dysfunction and personality and Behavior change is clinical manifestation, and onset is slow or concealment, disease incidence height are more common in 70 years old or more old man, there are about 8,000,000 in China AD patient, 65 years old prevalence of age > is 5%, and 80 years old crowd of age > is up to 40%.The cause of disease of Alzheimer disease is multiple It is miscellaneous, the generally result of the multifactor effect such as inherent cause, environmental factor and living habit.

Dull-witted main clinic symptoms are the decline of memory gradation, decrease of cognitive function, and some researches show that AD's is main The senile plaque and Protein tau Hyperphosphorylationof that pathological characters are formed for amyloid beta abnormal deposition lead to neurofibril It tangles.Dementia patients early memory decline, judgement decline, to things cognitive presence obstacle, and reaches an advanced stage, patient loses Self care ability is completely dependent on caregiver, and serious memory loss has and the primary reflections such as holds, gropes and suck by force, final dusk Fan, generally dies of the complication such as infection, this seriously affects the quality of life of patient, and to family bring heavy economic pressures and Corresponding nursing burden.

Dull-witted specific pathogenesis does not illustrate completely yet at present, and there are a variety of hypothesis, including inflammation theory, A β toxicity study It says, Protein tau modification theory, oxidative stress theory, cholinergic extremely damage theory etc., now clinically most commonly used AD treatment Drug is the acetylcholinesterase inhibitor damaging theory for cholinergic and using, and mainly includes Tacrine derivatives, kappa La Ting, huperzine are first-class, but since senile dementia pathology change procedure is considerably complicated, be related to multisystem, multiple target point it is different Often, and the problem of often there is unsatisfactory curative effect, lack targeting in the treatment of doctor trained in Western medicine chemical drug, toxicity is high, narrow application range.

Traditional Chinese medicine thinks the diseases scopes such as senile dementia category " slow-witted disease " " not intelligent " " melancholia " " forgetful ".Classical symptom is main It is embodied in cognitive decrease, behavior and phrenoblabia, 3 aspects based on viability decline.Traditional Chinese medicine thinks that human body declines Old den is kidney；Essence in kidney decides process of the growth and development up to aging of people.Kidney storing essence marrow, marrow are supplemented nutrition brain, Brain hiding intelligence, therefore the raw intelligence of essence.Kidney essense is full, and brain spill-over, then mesh can regard, and ear can be listened, and mouth can be sayed, energetic, conscious, instead Agility is answered, intelligence is sound, can correctly be analyzed objective things, judge, understands.Essence in kidney is abundant, then marrow fills mind It is prosperous, the material base for intelligence of not only having made a living, but also be the function basis that replenishing the brain and spinal cord plays intelligence.The elderly's kidney essense day with age It is gradually deficient, for a long time just cause emptiness of the essence and marrow, brain is become homeless feeding, gods mistake department, thus may be used with the common diseases such as forgetful, silly, dull Know deficiency of kidney-essence, brain gradually sky be senile dementia occurrence and development basic reason.

With advancing age, vigour increasingly lose in warm excitation by virtual loss, vital organs of the human body function, causes functional activity of QI being not smooth, saliva Liquid dysbolism can make intracorporal phlegm is turbid to be continuously increased, therefore forefathers have saying for " the more phlegm of old man ".Turbid phlegm blocking the clear orifices and dull-witted generation Closely related, phlegm retention blocks brain key, keeps and does not go, and agglomerates hardly possibleization, causes brain muddy, and clear sun blinds, and sudden inspiration is not transported, and refreshing machine loses It adjusts, dementia then comes into being, and clinic occurs staying that blunt forgetful, gurgling with sputum, mouth polysialia foam, heaviness sensation over the head and body, chest institute ruffian be bored, words top , movement is without the diseases such as, coma is demented." dialectical record " explicitly point out " phlegm product in brain, illegally occupy in outside the heart, making gods unclear and At dementia." thus, vigour virtual loss, sthenia symptoms caused by asthenia, turbid phlegm blocking the clear orifices are the important links of senile dementia morbidity.

The total interpretation of the cause, onset and process of an illness of senile dementia is asthenia in origin and asthenia in superficiality, this void is that deficiency of kidney-essence, brain dystrophy, member mind are not hidden, marks Really brain key is blinded in phlegm is turbid, and the two influences each other, reciprocal causation, collectively promotes the occurrence and development of senile dementia.It is based on The pathogenic characteristic of senile dementia simulataneous insufficiency and excessive, it then follows " simultaneous treatment of principal and subordinate symptoms ", " eliminating to treat the excess syndrome makes up a deficiency ", " strengthening vital QI to eliminate pathogenic factors ", The rules for the treatment of such as " treatinging deficiency with tonification, sthenia syndrome requiring purgation " are controlled using element culturing fixed folder, resolving sputum brain-care as prevention and treatment the important of senile dementia Method.

Chinese patent literature CN108853294A discloses a kind of pharmaceutical composition for treating vascular dementia, the medicine group Closing object is prepared by the raw material of following weight proportion: 10~30 parts of Rhizoma Chuanxiong, 5~20 parts of Radix Angelicae Sinensis, 1~15 part of radix scutellariae, stone Chang 1~12 part of Pu, 1~12 part of Poria cocos, 2~12 parts of Radix Polygalae, 1~12 part of ginseng.The present invention further discloses the pharmaceutical composition The specific preparation method and purposes of object.Show that pharmaceutical composition of the present invention can repair vascular dementia by pharmacological experiment study The impaired neuron linear plastochondria of rat model, the energetic supersession for improving cell in brain tissue, improve the learning and memory of rat model Ability, however the pharmaceutical composition only has preferable therapeutic effect to vascular dementia rat models, and more for pathology Complicated, more common senile dementia is ineffective, therefore, it is senile silly to study less toxic, effective and corresponding multiple target point treatment Slow-witted drug development has great importance.

Summary of the invention

Therefore, the technical problem to be solved in the present invention is that overcoming Chinese medicine composition target spot in the prior art few, curative effect Difference, the narrow problem of applicability, to provide a kind of Chinese medicine composition and the preparation method and application thereof.

The present invention provides a kind of Chinese medicine composition, the bulk pharmaceutical chemicals including following parts by weight: 2-15 parts of ginseng, Semen Ziziphi Spinosae (parched) 2-15 parts, 2-15 parts of Herba Epimedii Preparata, 3-18 parts of Rehmannia glutinosa, 1-12 parts of RADIX POLYGALAE PREPARATA, 1-12 parts of stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, 3-18 parts of Radix Angelicae Sinensis, stone 2-15 parts of calamus, 1-10 parts of radix glycyrrhizae preparata.

Further, the bulk pharmaceutical chemicals including following parts by weight: 4-9 parts of ginseng, 4-9 parts of Semen Ziziphi Spinosae (parched), Herba Epimedii Preparata 4-9 Part, 5-12 parts of Rehmannia glutinosa, 3-8 parts of RADIX POLYGALAE PREPARATA, 3-8 parts of stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, 5-12 parts of Radix Angelicae Sinensis, 4-9 parts of rhizoma acori graminei, 1-5 parts of radix glycyrrhizae preparata.

Preferably, institute's Chinese medicine composition obtains composition through smashing for each bulk pharmaceutical chemicals；Or after each bulk pharmaceutical chemicals mixing routinely Extracting method or the extract that routinely extracting method is extracted respectively；Or extract has by what polishing purification technique obtained Imitate part.

Further, the general extraction methods include Soakage extraction, decoct extraction, refluxing extraction, seepage pressure effects, ultrasound One or more of extraction and steam distillation；Extraction solvent includes water or 20-95vt% ethanol solution；The polishing purification Technique includes one or more of water extract-alcohol precipitation, extraction, silica gel chromatograph post separation and macroreticular resin post separation.

The present invention also provides a kind of methods for preparing the Chinese medicine composition, include the following steps:

(1) Radix Angelicae Sinensis and rhizoma acori graminei, extracting in water are weighed, steam distillation is extracted, and volatile oil and aqueous extract is obtained, to volatilization Betadex and water inclusion are added in oil, obtains inclusion compound；

(2) ginseng, radix rehmanniae preparata, RADIX POLYGALAE PREPARATA, stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, Semen Ziziphi Spinosae (parched), Herba Epimedii Preparata and radix glycyrrhizae preparata are weighed, extracting in water, Obtain aqueous extract；

(3) merge aqueous extract made from above-mentioned two step, clear cream is concentrated under reduced pressure to obtain；

(4) clear cream is dry, dried cream powder is made, the inclusion compound is added, mix to get.

Further, in step (1) extraction process, Radix Angelicae Sinensis and rhizoma acori graminei are taken, is smashed, addition accounts for Radix Angelicae Sinensis and rhizoma acori graminei gross weight The water of 8-12 times of amount impregnates 0.3-1h, and steam distillation extracts volatile oil, and extraction time 2-8h, obtains volatile oil and water extracts Liquid；

Preferably, during step (1) inclusion, betadex and water, grinding inclusion are added in the volatile oil 20-40min is stood, filtering, collects inclusion compound, and 30-50 DEG C of drying is spare；

Wherein, the amount ratio of the volatile oil and betadex and water is 1ml:4-12g:32-144ml.

The present invention also provides a kind of pharmaceutical preparations, using preparation described in the Chinese medicine composition or claim Chinese medicine composition made from method is that active component addition customary adjuvant is prepared according to common process.

Further, the pharmaceutical preparation is ointment, patch, liniment, lotion, solution, injection, spray, sugar Starch agent, Wet-dressing agent, suppository, tablet, pill, granule or capsule.

The Chinese medicine composition perhaps Chinese medicine composition or the drug system made from the preparation method Application of the agent in the drug of preparation treatment Alzheimer disease.

Technical solution of the present invention compared with prior art, has the advantages that

1, Chinese medicine composition provided by the invention, it is remote with ginseng, Semen Ziziphi Spinosae (parched), Herba Epimedii Preparata, Rehmannia glutinosa, rhizoma atractylodis macrocephalae, system Will, rhizoma acori graminei, Radix Angelicae Sinensis, radix glycyrrhizae preparata are that the Chinese medicine group with the effect of element culturing fixed folder, resolving sputum promoting blood circulation, brain-care is made in bulk pharmaceutical chemicals Object is closed, in described pharmaceutical composition, ginseng sweet temperature is reinforced vital energy, shengjin nourishing, tranquilize the mind and promote the intelligence；The sweet tepor of radix rehmanniae preparata, taste of enriching blood Yin, beneficial to spirit and marrow；Herba Epimedii Xin Ganwen, tonifies the kidney and support yang.Three medicines match, and are combined into monarch drug in a prescription, nourishing qi and blood, kidney tonifying, essence replenishing, to consolidate Qi-restoratives.It is flat to be added with semen ziziphi spinosae sweet acid, nourishing heart tonifying liver, antitoxic heart-soothing and sedative；Radix Polygalae is toil and warm, tranquilize the mind and promote the intelligence, restoring normal coordination between heart and kidney.The two is altogether Ministerial drug is calmed the nerves with auxiliary monarch drug in a prescription bushing nourishing the liver and is increased intelligence.Menstruation disorder causing edema, the not behavior stasis of blood select Radix Angelicae Sinensis Gan Xinwen, replenishing and activating blood；It fries Rhizoma Atractylodis Macrocephalae bitter sweet temperature, strengthening the spleen and replenishing qi, eliminate dampness and have diuretic effect.Phlegm and blood stasis stores accumulateing of knot, always through disease, except the stasis of blood does not forget eliminating the phlegm, selects Rhizoma acori graminei is bitter and warm, slit phlegm of having one's ideas straightened out, inducing resuscitation intelligence development, dampness elimination appetizing, closes Radix Polygalae and reinforces phlegm-dispelling functions.Three is adjutant, exempting from altogether Phlegm-blood stasis, tonneau qi and blood.Make, tonifying spleen stomach function regulating sweet flat with radix glycyrrhizae preparata, Yiqi and vein recovery, help help and with all medicines；Complete square compatibility 5 is rigorous, mark This with controlling, play altogether training vigour, tonifying five zang organs, resolving sputum promoting blood circulation, brain-care function.

2, pharmaceutical composition primary treatment senile dementia illness of the present invention, is controlled in terms for the treatment of senile dementia Therapeutic effect is significant, feeds back through animal pharmacodynamic experiment and later phase clinical, and the party treats that senile dementia target spot is more, safety High, good effect, applicability are wide；Pharmaceutical composition of the present invention is foundation traditional medical theory, and applicant is combined to face for many years Bed experience, for the etiology and pathogenesis of senile dementia, establish with element culturing fixed folder, resolving sputum promoting blood circulation, brain-care method compatibility Prescription.

3, the Chinese medicine composition preparation method of element culturing fixed folder intelligence development of the present invention is simple, easy to operate, by adjusting original Expect that medicine selects suitable extracting method, wherein Radix Angelicae Sinensis and rhizoma acori graminei elder generation water extract again steam distillation extract to obtain aqueous extract and Volatile oil will volatilize oil and inclusion compound is made, and ginseng, radix rehmanniae preparata, RADIX POLYGALAE PREPARATA, stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, Semen Ziziphi Spinosae (parched), Herba Epimedii Preparata and toast is sweet Grass, which is adopted, to be extracted with water to obtain aqueous extract, and aqueous extract is mixed concentration and is mixed with inclusion compound, so that manufactured Chinese medicine composition Middle active constituent content significantly improves, and impurity content is also significantly reduced, and then the treatment improved to senile dementia is imitated Fruit guarantees the safety used.

Detailed description of the invention

In order to make the content of the present invention more clearly understood, it below according to specific embodiments of the present invention and combines Attached drawing, the present invention is described in further detail, wherein

Fig. 1 is that Chinese medicine composition described in the embodiment of the present invention 1 tests IBO model AD treated rats in Morris water maze performance Figure；Wherein a is incubation period training stage；B is representative motion profile；

Fig. 2 is Chinese medicine composition described in the embodiment of the present invention 1 to IBO model AD rat step-through test figure；A is QFY Dark preclinical influence result is kept away on IBO rat model；B is the influence result that QFY keeps away IBO rat model dark errors number；

Fig. 3 is Chinese medicine composition described in the embodiment of the present invention 1 to IBO model AD rat HE coloration result figure (x200)；From a-h, it is followed successively by normal group, sham-operation group, model group, positive drug group, low dose group, middle dose group, high dose group With water decoction group；

Fig. 4 and Fig. 5 is that Chinese medicine composition described in the embodiment of the present invention 1 tests IBO model AD rat Nissl's staining Result figure；In Fig. 4, from a-h, it is followed successively by normal group, sham-operation group, model group, low dose group, middle dose group, high dose group, water Buddhist nun's formula coloration result (× 400) of decoction group and positive drug group；In Fig. 5, a is the IOD value of Nissl's staining, and b is Buddhist nun's formula dyeing mind Through first quantity；

Fig. 6 and Fig. 7 is that Chinese medicine composition described in the embodiment of the present invention 1 is real to IBO model AD rat ChAT immunohistochemistry Test result figure；In Fig. 6, from a-d, be followed successively by normal group, sham-operation group, model group, low dose group, middle dose group, high dose group, The ImmunohistochemistryResults Results (× 400) of water decoction group and positive drug group；Fig. 7 is ChAT positive cell number, note: P < 0.05 *, and normal Group compares；#P < 0.05, compared with model group；

Fig. 8 is Chinese medicine composition described in the embodiment of the present invention 1 to A β model AD treated rats in Morris water maze performance lab diagram； Wherein a is incubation period training stage；B is representative motion profile；

Fig. 9 is Chinese medicine composition described in the embodiment of the present invention 1 to A β model AD rat step-through test figure；A is QFY Dark preclinical influence result is kept away on A β rat model；B is the influence result that QFY keeps away A β rat model dark errors number；

Figure 10 is Chinese medicine composition described in the embodiment of the present invention 1 to A β model AD rat HE coloration result figure (x200)；From a-h, it is followed successively by normal group, sham-operation group, model group, positive drug group, low dose group, middle dose group, high dose group With the HE coloration result (× 400) of water decoction group；

Figure 11 and Figure 12 is Chinese medicine composition described in the embodiment of the present invention 1 to A β model AD rat ChAT immunohistochemistry Experimental result picture；From a-h, it is followed successively by normal group, sham-operation group, model group, low dose group, middle dose group, high dose group, decocting The ImmunohistochemistryResults Results (× 400) of agent group and positive drug group；It is ChAT positive cell number in Figure 12；

Figure 13 is that Chinese medicine composition described in the embodiment of the present invention 1 is real to APP/PS1 transgenic mice Morris water maze Test figure；Wherein a is training stage visible platform incubation period；B is the incubation period for hiding mouse in platform experiment；C is representative fortune Dynamic rail mark；

Figure 14 is Chinese medicine composition described in the embodiment of the present invention 1 to APP/PS1 transgenic mice HE coloration result figure (x200)；From a-g, it is followed successively by wild control group, non-transgenic control group, positive controls, low dose group, middle dose group, high agent Amount group and water decoction group；

Figure 15 is Chinese medicine composition described in the embodiment of the present invention 1 to APP/PS1 transgenic mice α secretase immune group Change coloration result (× 400)；From a-g, it is followed successively by normal group, model group, low dose group, middle dose group, high dose group, water decoction The α secretase immunohistochemical staining result of group and positive drug group；

Figure 16 is Chinese medicine composition described in the embodiment of the present invention 1 to APP/PS1 transgenic mice beta-secretase immune group Change coloration result (× 400)；From a-g, it is followed successively by normal group, model group, low dose group, middle dose group, high dose group, water decoction The α secretase immunohistochemical staining result of group and positive drug group；

Figure 17 is that Chinese medicine composition described in the embodiment of the present invention 1 is immune to APP/PS1 transgenic mice gamma secretase Histochemical staining result (× 400)；From a-i, it is followed successively by normal group, model group, low dose group, middle dose group, high dose group, decocting The α secretase immunohistochemical staining result of agent group and positive drug group；

Figure 18 is that Chinese medicine composition described in the embodiment of the present invention 1 is immune to APP/PS1 transgenic mice gamma secretase Groupization result, wherein a is α secretase immunohistochemistry positive cell number；B is beta-secretase immunohistochemistry positive cell number；C is γ Secretase immunohistochemistry positive cell number.

Experimental example

Anti-Alzheimer disease experimental study of the Chinese medicine composition described in experimental example 1 to goose cream Tan propylhomoserin rat

1. experiment purpose

By goose cream Tan propylhomoserin induced rat Alzheimer's disease model (IBO model), Chinese traditional medicine composition of the invention is observed Object to the behaviouristics of IBO model, cholinergic nerve system, response to oxidative stress, pathological change influence, evaluate the Chinese traditional medicine composition The anti-Alzheimer disease of object acts on.

2. experimental material

2.1 drug

(1) the water decoction group of Chinese medicine composition

Composition: ginseng 6g, Semen Ziziphi Spinosae (parched) 6g, Herba Epimedii Preparata 6g, radix rehmanniae preparata 9g, stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran 5g, 5g parts of RADIX POLYGALAE PREPARATA, rhizoma acori graminei 6g, Radix Angelicae Sinensis 9g, radix glycyrrhizae preparata 3g；

Preparation method: taking Radix Angelicae Sinensis and semen ziziphi spinosae, smashes, and decocts twice, adds water to cook twice, adds 120g water for the first time, impregnates 0.5h, decocts 30min, and second plus 90g water decoct 20min.Decoction liquor crosses 120 meshes, filtering, merging filtrate, true at 55 DEG C Sky is concentrated into every 1ml concentrate crude drug amount containing 1g to get lot number 20171101；Specification is 1.0g crude drug/1ml concentrate.

(2) extract (hereinafter referred to as " QFY extract ") of Chinese medicine composition:

Preparation method: taking Radix Angelicae Sinensis and rhizoma acori graminei, smashes into coarse granule, and 150g water is added to impregnate 0.5h, and steam distillation extracts 6h, point Not Shou Ji volatile oil and aqueous extract, be added betadex and water into volatile oil, grinding inclusion 40min is stood at 4 DEG C For 24 hours, it filters, obtains inclusion compound, 40 DEG C of drying are spare, and wherein the quality of water is 64 times of volatilization oil quality, the matter of betadex Amount is 8 times of volatilization oil quality；Ginseng, radix rehmanniae preparata, RADIX POLYGALAE PREPARATA, stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, Semen Ziziphi Spinosae (parched), Herba Epimedii Preparata, radix glycyrrhizae preparata are weighed, it will Ginseng, Semen Ziziphi Spinosae (parched) are broken, are separately added into the water of 12 times of medicinal material weight, impregnate 0.5h, decoct 2 times, 1 hour every time, merge and decoct It is filtered after boil liquid, obtains extracting solution, it is spare；Merge aqueous extract made from two steps, being concentrated under reduced pressure into relative density at 50 DEG C is 1.30 clear cream；Clear cream is subjected to vacuum belt type drying, dried cream powder is made, the inclusion compound is added, is mixed to get lot number is TQ170928；Character is sundown to yellowish-brown powder, and mildly bitter flavor, sweet tea are soluble easily in water；Specification is that 4.0g crude drug/g is extracted Object.

(3) donepezil piece (Aricept), lot number: 1609047, Pharmaceutical Co., Ltd. of health material

2.2 main agents

Ammonium hydroxide (analysis is pure), disodium hydrogen phosphate dodecahydrate are provided by Xilong Chemical Co., Ltd, goose cream Tan propylhomoserin (IBO) purchased from odd trade Co., Ltd in the sea difficult to understand, Sigma；Sodium carboxymethylcellulose, chloraldurate are purchased from Chinese medicines group chemistry Reagent Co., Ltd；Hydrochloric acid, 3% hydrogen peroxide and sodium chloride etc. are purchased from Nanjing chemical reagent limited liability company；0.9% Sodium chloride injection is purchased from Anhui Co., Ltd, Double-Crane Pharmaceutical Co., Ltd；Iodophor is purchased from Xinghua City medical and hygiene article Co., Ltd；Acetyl Choline (Ach) assay kit, acetylcholinesterase (AChE) assay kit, acetylcholine transferase (ChAT) measure reagent Box, glutathione reductase (GR assay kit), glutathione peroxidase (GSH-PX) testing cassete, catalase (CAT) testing cassete, total number born (T-SOD) testing cassete, malonaldehyde (MDA) testing cassete, total protein quantitative test box Biomaterials such as (BCA methods) build up Bioisystech Co., Ltd purchased from Nanjing.

2.3 experimental animals and raising situation

(1) experimental animal

SPF grades of SD rats, 180-220g, half male and half female.Purchased from Jiangning county Qinglongshan animal reproduction field, animal is raw Produce credit number: SCXK (Soviet Union) 2017-0001, quality certification number: 201722755.

(2) rearing conditions

By above-mentioned experimental animal feeding in 21-26 DEG C, the environment of relative humidity 40-70%, animal freely ingests, drinks Water.

2.4 major experimental instruments

DW-2000 stereotaxic apparatus is purchased from Chengdu TME Technology Co., Ltd.；CD-200 animal cranial drill, purchased from Science and Technology Ltd., Dou Tai alliance；The labyrinth Y is purchased from Shanghai Yishu Information Technology Co., Ltd.；Step-through test device is moved purchased from Shanghai Number Information technology Co., Ltd；Morris water maze is purchased from Jiliang Software Sci-Tech Co., Ltd., Shanghai, etc..

3. experimental method

The setting of 3.1 dosages

1 given the test agent rat taking dose of table

Grouping	Administered volume	Crude drug dosage	Dosage
				Normal group	5ml/kg/d	—	5ml/kg
Sham-operation group	5ml/kg/d	—	5ml/kg
				Model group	5ml/kg/d	—	5ml/kg
Donepezil positive drug group	5ml/kg/d	—	0.5mg/kg
				Water decoction group	5ml/kg/d	5.00g/kg	5.00g/kg
QFY low dosage medical fluid group	5ml/kg/d	3.80g/kg	0.95g/kg
				QFY middle dosage medical fluid group	5ml/kg/d	7.60g/kg	1.90g/kg
QFY high dose medical fluid group	5ml/kg/d	15.20g/kg	3.80g/kg

3.2 drugs are prepared

(1) it the high, medium and low dosage group medical fluid of QFY: accurately weighs QFY extract 38.0g, CMC-Na containing 0.5wt% is added Aqueous solution, ultrasonic 2h mixes well, and is settled to 50ml to get QFY high dose medical fluid；Measure 25ml QFY high dose medicine The aqueous solution containing 0.5wt%CMC-Na is added in liquid, is settled to 50ml, mixes to get QFY middle dosage medical fluid；Measure 25ml QFY middle dosage medical fluid, the aqueous solution containing 0.5wt%CMC-Na are settled to 50ml, mix to get QFY low dosage medical fluid.

(2) positive drug group medical fluid: taking a piece of donepezil piece (content 5mg), is added containing the water-soluble of 0.5wt%CMC-Na Liquid, ultrasonic 2h, mixes well, and is settled to 50ml to get positive drug medical fluid.

3.3 zooperies grouping

After experimental animal adaptive feeding 10 days, rat is randomly divided into 8 groups, and every group male rat 6, female rats 6 Only.Be respectively as follows: normal group, sham-operation group, model group, donepezil positive drug group, QFY high dose group, QFY middle dose group, QFY low dose group, water decoction group.

Dementia in Rats mould is established using stereotaxic technique bilateral basal core injection IBO (5 μ g/ μ l are dissolved in PBS) 1 μ l Type screens AD rat model by Y maze experiment.Inject the rat group of IBO are as follows: model group, QFY high dose group, agent in QFY Amount group, QFY low dose group, water decoction group, donepezil positive drug group, the isometric PBS of sham-operation group (12) injections, just Normal control group is without injection, administration after the 12nd day rat is in stable condition after modeling.

3.4 medication

Administration route is oral pipe gastric infusion, and administered volume is 5ml/kg weight rat.

Each group gives following drug: normal group, sham-operation group and model group: 0.5% CMC-Na 5ml/kg/d；It is positive Medicine group: donepezil piece 0.5mg/kg；QFY high dose group: 3.80g/kg, QFY middle dose group: 1.90g/kg, QFY low dosage Group: 0.95g/kg, water decoction group: 5.00g/kg.

3.5 experimental method

Institute's reagent object is given in stomach-filling to each group rat respectively, and every afternoon, administration, continuous 4 weeks, weighed weekly during administration To adjust dosage.

By Morris water maze laboratory, rat is recorded in the original platform residence time by computer and passes through original platform Number；Record in maze experiment that rat is greatly into arm total degree N, spontaneous alternation response rate, rat leaves peace for the first time in step-through test The time of the whole district and errors number；By HE decoration method, Nissl's colouring, ChAT immunohistochemistry, the pathology at brain tissue is monitored Variation；By biochemical detection methods, the cholinergic nerves such as Ach content, AChE enzyme activity and ChAT enzyme activity in brain tissue are measured Correlation factor analyzes the activity of antioxidant enzyme SOD, GSH-PX, GR and CAT and the content of Lipid peroxidation index MDA, It is horizontal to monitor response to oxidative stress.

4 statistical methods

Experimental data is indicated with " mean+SD ", is analyzed using one-way analysis of variance method.Compare between group Compared with when, homogeneity of variance using LSD examine；Heterogeneity of variance selects Dunnett ' s T3 to examine.

5. experimental result

The influence that 5.1QFY extract tests AD treated rats in Morris water maze performance

The influence (n=10) that 2 QFY of table tests AD treated rats in Morris water maze performance

Group	Wear platform number (mean+SD)
		Normal group	4.38±0.41
Sham-operation group	3.88±0.73
		Model group	1.50±0.48^##
QFY(0.95g/kg)	4.00±0.48^**
		QFY(1.90g/kg)	4.00±0.41^**
QFY(3.80g/kg)	4.25±0.27^**
		Water decoction group	4.00±0.38^**
Donepezil group	3.88±0.66^**

^#P<0.05,^##P<0.01,^###P < 0.001vs. sham-operation group；^*P<0.05,^**P<0.01,^***P < 0.001vs. model Group

The experimental results showed that AD rat model shows longer incubation period as shown in Fig. 1 (a) compared with sham-operation group, Show the damage of its space learning exploring ability；Compared with AD model group, QFY each dosage group incubation period is obviously shortened, and there are poles Significant difference (P < 0.01).After withdrawing from platform, as shown in table 1, platform number is worn in 90s after sham-operation group training and is obviously compared AD group is more (P < 0.01)；Compared with AD model group, what each dosage group of QFY significantly improved rat wears platform number.

This result of study shows that the decocting liquid of the traditional chinese medicine composition of the invention and high, medium and low dosage group have preferable anti-Ah Er Cihaimo disease effect.

Influence of the 5.2QFY extract to AD rat Y maze experiment

Influence (n=10) of 3 QFY of table to AD rat model Y maze experiment

Calculation formula: spontaneous alternation response rate (%)=[correct alternation response number/(N-2)] × 100%；

As shown in table 3, compared with sham-operation group, the spontaneous alternation response rate of AD rat model is significantly reduced, and shows its space The damage of memory capability.Compared with AD model group, the spontaneous alternation response rate of each dosage group of QFY all dramatically increases (0.95g/kg:P < 0.05,1.90g/kg:P < 0.05,3.80g/kg:P < 0.01, water decoction group: P < 0.01).

The experimental results showed that the learning and memory energy of decocting liquid, the traditional chinese medicine composition of the invention of various dose group to AD rat Power has improvement result.

Influence of the 5.3QFY extract to AD rat step-through test

Influence (n=10) of 4 QFY of table to AD rat model step-through test

As shown in table 4 and Fig. 2, compared with sham-operation group, there are certain shortening, errors number in the incubation period of AD rat model There is certain increase, shows the damage of its ability of learning and memory.Compared with AD model group, QFY each dosage group incubation period increases, wrong Accidentally number is reduced.

The result shows that decocting liquid, the traditional chinese medicine composition of the invention of various dose group have the ability of learning and memory of AD rat There is improvement result.

Influence of the 5.4QFY to AD rat cholinergic nerve system

Influence (n=of 5 QFY of table to Ach content, AChE enzyme activity and ChAT enzyme activity in AD rat model brain tissue 8)

^#P < 0.05,^##P<0.01,^###P < 0.001vs. sham-operation group；^*P<0.05,^**P<0.01,^***P < 0.001vs. model Group

As shown in table 5, compared with sham-operation group, the Ach content of AD rat model, AChE vigor and ChAT vigor are significant Property reduce (P < 0.01), show that the cholinergic nerve transmitting of rat is impaired.Compared with AD model group, Ach content is at each dose of QFY Amount group all shows conspicuousness and increases (0.95g/kg:P < 0.05,1.90g/kg:P < 0.01,3.80g/kg:P < 0.01, decocting Agent group: P < 0.05)；AChE vigor shows conspicuousness in each dosage group of QFY and increases (0.95g/kg:P < 0.05,1.90g/ Kg:P < 0.01,3.80g/kg:P < 0.01, water decoction group: P < 0.01), and ChAT vigor is in the middle and high dosage group of QFY and decocting Agent group all shows conspicuousness and increases (1.90g/kg:P < 0.05,3.80g/kg:P < 0.01, water decoction group: P < 0.01), as a result Show that the traditional chinese medicine composition of the invention improves significantly to the cholinergic system of rat.

Influence of the 5.5QFY to AD rat response to oxidative stress

Influence (n=8) of 6 QFY of table to AD rat model response to oxidative stress

As shown in table 6, compared with sham-operation group, the antioxidant enzyme SOD vigor of AD rat model, GR vigor conspicuousness drop Low (P < 0.001) and MDA content dramatically increases (P < 0.01), show that AD model group shows significant response to oxidative stress.

Compared with AD model group, SOD vigor each dosage group of QFY all show conspicuousness increase (0.95g/kg:P < 0.01,1.90g/kg:P < 0.001,3.80g/kg:P < 0.001, water decoction group: P < 0.001)；Compared with AD model group, GR is living Power all shows conspicuousness in each dosage group of QFY and increases (0.95g/kg:P < 0.05,1.90g/kg:P < 0.05,3.80g/kg:P < 0.01, water decoction group: P < 0.05)；Compared with AD model group, MDA content all shows conspicuousness reduction in each dosage group of QFY (0.95g/kg:P < 0.05,1.90g/kg:P < 0.05,3.80g/kg:P < 0.05, water decoction: P < 0.01)；GSH-PX and CAT Vigor there is no a significant change, after result above shows QFY administration, the oxidative stress in rat brain is significantly changed It is kind.

5.6HE coloration result

As shown in figure 3, compared with normal group, sham-operation group has no obvious pathological change, model group hippocampus in HE dyeing Area and cerebral cortex are shown in neuron oedema；Compare between QFY various dose group, in, low dose group lesion degree it is suitable, lesion Degree higher dosage group is slightly heavy, and water decoction group lesion degree has no substantially reduced compared with model group；Compared with model group, positive drug group It is also reduced to varying degrees with test drug QFY group lesion degree compared with model group.

This result of study shows compared to model group and water decoction group, the quenchable IBO model of QFY extract of the present invention AD rat lesion.

5.7 Nissl's staining results

As shown in Figures 4 and 5, compared with normal group, tigroid body is bright in model group brain tissue hippocampus neuron and neuron It is aobvious to reduce, but without obvious statistical difference；Compared with model group, Buddhist nun in positive drug group brain tissue hippocampus neuron and neuron Family name's body slightly increases, the different degrees of increasing of tigroid body in QFY low, middle and high dose groups brain tissue hippocampus neuron and neuron Add, and there is dosage correlation, without obvious statistical difference, Nissl in water decoction group brain tissue hippocampus neuron and neuron Body slightly increases.

5.8ChAT immunohistochemistry

ChAT ImmunohistochemistryResults Results, as shown in Figures 6 and 7, compared with normal group, model group brain tissue neuron ChAT table (P < 0.05) is substantially reduced up to amount；Compared with model group, QFY low, middle and high dose groups brain tissue neuron ChAT expression quantity has Different degrees of raising, and there is dosage correlation, high dose group brain tissue neuron ChAT expression quantity obviously increases (3.80g/ kg:P<0.05)；Water decoction group and positive drug group brain tissue neuron ChAT expression quantity are increased compared with model group, but poor without statistics It is different.

This result of study shows that QFY extract of the present invention is to cholinergic nerve elementary work compared to model group and water decoction group There can be inhibition degeneration.

Anti-Alzheimer disease experimental study of the Chinese medicine composition described in experimental example 2 to beta-amyloid protein rat

1. experiment purpose

By in rats with bilateral hippocampal injection beta-amyloid protein induced rat Alzheimer's disease model (A β rat mould Type), observe behaviouristics of the traditional chinese medicine composition of the invention to the model, brain tissue inflammation's reaction, response to oxidative stress, pathological change Influence, evaluate the traditional chinese medicine composition of the invention anti-Alzheimer disease effect.

2. experimental material

2.1 drug

(1) the water decoction group of the traditional chinese medicine composition of the invention

Composition: ginseng 6g, Semen Ziziphi Spinosae (parched) 6g, Herba Epimedii Preparata 6g, radix rehmanniae preparata 9g, rhizoma atractylodis macrocephalae 5g, 5g parts of RADIX POLYGALAE PREPARATA, rhizoma acori graminei 6g, Radix Angelicae Sinensis 9g, radix glycyrrhizae preparata 3g；

(2) extract (hereinafter referred to as " QFY extract ") of the traditional chinese medicine composition of the invention:

(3) donepezil piece (Aricept), lot number: 1702011, Pharmaceutical Co., Ltd. of health material

2.2 main agents

Ammonium hydroxide (analysis is pure), disodium hydrogen phosphate dodecahydrate are provided by Xilong Chemical Co., Ltd, A-OK amyloid Albumen is purchased from Shanghai Yuan Ye Biotechnology Co., Ltd；Sodium carboxymethylcellulose, chloraldurate are purchased from the examination of Chinese medicines group chemistry Agent Co., Ltd；Hydrochloric acid, 3% hydrogen peroxide and sodium chloride etc. are purchased from Nanjing chemical reagent limited liability company；0.9% chlorination Sodium injection is purchased from Anhui Co., Ltd, Double-Crane Pharmaceutical Co., Ltd；Iodophor is purchased from Xinghua City medical and hygiene article Co., Ltd；Glutathione Reductase (GR assay kit), glutathione peroxidase (GSH-PX) testing cassete, catalase (CAT) testing cassete, Total number born (T-SOD) testing cassete, malonaldehyde (MDA) testing cassete, total protein quantitative test box (BCA method) are purchased from south Bioisystech Co., Ltd is built up in capital；Rat interleukin-11 β (IL-1 β) enzyme-linked immunosorbent assay kit and rat tumor are bad Necrosis factor α (TNF-α) enzyme-linked immunosorbent assay kit is purchased from Elabscience；Deng.

2.3 experimental animals and raising situation

(1) experimental animal

SPF grades of SD rats, 180-220g, half male and half female.Purchased from Jiangning county Qinglongshan animal reproduction field, animal is raw Produce credit number: SCXK (Soviet Union) 2013-0006, quality certification number: 311620400010972.

(2) rearing conditions

2.4 major experimental instruments

DW-2000 stereotaxic apparatus is purchased from Chengdu TME Technology Co., Ltd.；CD-200 animal cranial drill, purchased from Science and Technology Ltd., Dou Tai alliance；The labyrinth Y is purchased from Shanghai Yishu Information Technology Co., Ltd.；Step-through test device is moved purchased from Shanghai Number Information technology Co., Ltd；Morris water maze is purchased from Jiliang Software Sci-Tech Co., Ltd., Shanghai；Deng.

3. experimental method

The setting of 3.1 dosages

7 given the test agent rat taking dose of table

3.2 drugs are prepared

(1) it the high, medium and low dosage group medical fluid of QFY: accurately weighs QFY extract 38.0g, CMC-Na containing 0.5wt% is added Aqueous solution, ultrasonic 2h mixes well, and is settled to 50ml to get QFY high dose medical fluid；Measure 25ml QFY high dose medicine The aqueous solution containing 0.5wt%CMC-Na is added in liquid, is settled to 50ml, mixes to get QFY middle dosage medical fluid；Measure 25ml The aqueous solution containing 0.5wt%CMC-Na is added in QFY middle dosage medical fluid, is settled to 50ml, mixes to get QFY low dosage medical fluid.

(2) positive drug group medical fluid: taking a piece of donepezil piece (content 5mg), and 0.5%CMC-Na is added, and ultrasonic 2h fills Divide and mix, is settled to 50ml to get positive drug medical fluid.

3.3 zooperies grouping

Model of Dementia in Rats is established using stereotaxic technique bilateral hippocampus injection A β (2 μ g/ μ l are dissolved in PBS) 5 μ l, is led to Cross Y maze experiment screening AD rat model.Inject A β rat group are as follows: model group, QFY high dose group, QFY middle dose group, QFY low dose group, water decoction group, donepezil positive drug group, the isometric PBS of sham-operation group (12) injections, normal control Group is without injection, administration after the 12nd day rat is in stable condition after modeling.

3.4 medication

3.5 experimental method

By Morris water maze laboratory, rat is recorded in the original platform residence time by computer and passes through original platform Number；Record in maze experiment that rat is greatly into arm total degree N, spontaneous alternation response rate, rat leaves peace for the first time in step-through test The time of the whole district and errors number；By HE decoration method, ChAT immunohistochemistry, the pathological change at brain tissue is monitored；Pass through life Change detection method, measurement rat cerebral tissue IL-1 β, TNF-α content to analyze inflammatory reaction variation, and with antioxidant enzyme The activity analysis of SOD, GSH-PX, GR and CAT and the content of Lipid peroxidation index MDA monitor response to oxidative stress water It is flat.

4. statistical method

5. experimental result

The influence (n=10) that 8 QFY of table tests AD treated rats in Morris water maze performance

Group	Wear platform number (means standard deviation)
		Normal group	2.90±0.61
Sham-operation group	2.63±0.60
		Model group	0.88±0.40^##
QFY(0.95g/kg)	1.50±0.46
		QFY(1.90g/kg)	2.00±0.46
QFY(3.80g/kg)	2.25±0.37^*
		Water decoction group	2.00±0.60
Donepezil group	2.75±0.90^**

As shown in Figure 8 a, with the increase of training number of days, each group rat finds the incubation period of platform in the trend shortened.With Sham-operation group is compared, and AD rat model shows longer incubation period, shows the damage of its space learning exploring ability.With AD mould Type group is compared, and QFY each dosage group incubation period is obviously shortened.As shown in table 8 and Fig. 8 b, after withdrawing from platform, sham-operation group instruction Platform number obviously (P < 0.01) more than AD group are worn after white silk in 90s.Compared with AD model group, QFY high dose group is dramatically increased greatly Mouse wears platform number (3.80g/kg:P < 0.05), the above result shows that, the spatial memory capacity of rat is improved after administration.

Influence of the 5.2QFY extract to AD rat Y maze experiment

Influence (n=10) of 9 QFY of table to AD rat model Y maze experiment

Group	Spontaneous alternation response rate (%) (means standard deviation)
		Normal group	71.11±1.60
Sham-operation group	75.06±3.33
		Model group	54.02±2.80^###
QFY(0.95g/kg)	67.22±4.62^**
		QFY(1.90g/kg)	67.37±4.75^**
QFY(3.80g/kg)	72.10±4.36^***
		Water decoction group	70.11±2.44^**
Positive controls	68.90±3.86^**

As shown in table 9, compared with sham-operation group, the spontaneous alternation response rate of AD rat model is significantly reduced, and shows its space The damage (P < 0.001) of memory capability.Compared with AD model group, the spontaneous alternation response rate of each dosage group of QFY is all dramatically increased (0.95g/kg:P < 0.01,1.90g/kg:P < 0.01,3.80g/kg:P < 0.001, water decoction group: P < 0.01).

Influence of the 5.3QFY to AD rat step-through test

Influence (n=10) of 10 QFY of table to AD rat model step-through test

Group	Incubation period (Sec) (means standard deviation)	Errors number (means standard deviation)
			Normal group	174.60±45.94	0.70±0.17
Sham-operation group	159.00±52.80	0.70±0.21
			Model group	75.80±42.01	1.70±0.41
QFY(0.95g/kg)	135.70±50.44	1.10±0.42
			QFY(1.90g/kg)	145.40±47.79	1.00±0.37
QFY(3.80g/kg)	158.90±52.17	0.70±0.24
			Water decoction group	140.50±50.62	1.20±0.40
Positive controls	155.20±47.62	0.90±0.35

As shown in table 10 and Fig. 9, compared with sham-operation group, there are certain shortening, mistake time in the incubation period of AD rat model Number has certain increase, shows the damage of its ability of learning and memory.Compared with AD model group, QFY each dosage group incubation period increases, Errors number is reduced.

The influence that 5.4QFY reacts AD rat inflammation

Influence (n=8) of 11 QFY of table to AD rat model inflammatory reaction

Group	IL-1 β (pg/mg protein) (means standard deviation)	TNF-α (pg/mg protein) (means standard deviation)
			Normal group	25.35±0.94	64.63±2.26
Sham-operation group	24.49±1.00	64.53±2.59
			Model group	29.44±0.94^##	73.34±3.46^#
QFY(0.95g/kg)	27.12±0.94	68.87±3.43
			QFY(1.90g/kg)	26.97±0.69	64.75±3.43
QFY(3.80g/kg)	25.10±0.97^**	64.33±2.39^*
			Water decoction group	25.44±1.71^*	63.57±3.07^*
Donepezil group	24.76±1.65^**	61.93±3.47^*

As shown in table 11, compared with sham-operation group, the IL-1 β content (P < 0.01) and TNF-α content of AD rat model (P < 0.05) it all obviously increases.Compared with model group, the IL-1 β content of QFY high dose group and water decoction group (3.80g/kg:P < 0.01, water decoction group: P < 0.05) and TNF-α content (3.80g/kg:P < 0.05, water decoction group: P < 0.05) show conspicuousness It reduces, shows that the traditional chinese medicine composition of the invention can be relieved the inflammatory reaction during Alzheimer's disease.

Influence of the 5.5QFY to AD rat response to oxidative stress

Influence (n=8) of 12 QFY of table to AD rat model response to oxidative stress

As shown in table 12, compared with sham-operation group, antioxidant enzyme SOD vigor, GR vigor, the CAT of AD rat model are living Power and GPX vigor conspicuousness reduce (P < 0.01), and MDA content dramatically increases (P < 0.01), shows that AD model group shows significantly Response to oxidative stress.Compared with AD model group, SOD vigor, GPX vigor show conspicuousness in QFY high dose group and increase ((3.80g/kg:P<0.01)；GR vigor shows conspicuousness in QFY high dose group and increases (3.80g/kg:P < 0.05)；CAT is living Power shows conspicuousness in QFY high dose group and water decoction group and increases (3.80g/kg:P < 0.01, water decoction group: P < 0.05)； And MDA content QFY high, middle dose group and water decoction group show conspicuousness reduce (1.90g/kg:P < 0.05,3.80g/kg: P < 0.05, QFY-W:P < 0.01).

After result above shows QFY administration, the oxidative stress in rat brain is significantly improved.

5.6HE coloration result

As shown in Figure 10, in HE dyeing, compared with normal group, sham-operation group brain tissue has no obvious pathological change, mould Type group is shown in the different degrees of cell space shrinkage of brain tissue hippocampus neuron, and quantity is reduced；Compared with model group, positive drug group lesion Degree is substantially reduced, and each dosage group lesion degree of QFY is also also reduced to varying degrees compared with model group；The disease of low, middle and high dose groups Reducing tendency is presented in change degree, has certain dosage correlation, and water decoction group lesion degree mitigates compared with model group.

This result of study shows the quenchable A β model AD rat lesion of the traditional chinese medicine composition of the invention.

5.7ChAT immunohistochemistry

As shown in FIG. 11 and 12, compared with normal group, model group brain tissue neuron ChAT expression quantity is reduced, but without significant Statistical difference；Compared with model group, positive drug group brain tissue neuron ChAT expression quantity is increased, QFY low, middle and high dose groups Brain tissue neuron ChAT expression quantity increases in various degree, has dosage correlation, water decoction group brain tissue neuron ChAT table It is increased up to amount, but each group is compared with model group, no difference of science of statistics.

The result shows that the traditional chinese medicine composition of the invention has certain inhibition degeneration to cholinergic nerve meta function.

Chinese medicine composition described in experimental example 3 grinds the anti-Alzheimer disease experiment of APP/PS1 transgenic mice AD model Study carefully

1. experiment purpose

Establish APP/PS1 transgenic mice AD model, behaviouristics of the observation the traditional chinese medicine composition of the invention to the model, oxidation The anti-Alzheimer disease effect of the traditional chinese medicine composition of the invention is evaluated in stress reaction, pathological change and the influence of A β 1-42 content.

2. experimental material

2.1 drug

2.2 main agents

Sodium carboxymethylcellulose, chloraldurate are purchased from Sinopharm Chemical Reagent Co., Ltd.；Two hypophosphite monohydrate dihydros Sodium, disodium hydrogen phosphate dodecahydrate are provided by Xilong Chemical Co., Ltd, and A-OK amyloid protein is purchased from Shanghai source Ye Sheng Object Science and Technology Ltd.；Hydrochloric acid is purchased from Nanjing chemical reagent limited liability company；0.9% sodium chloride injection is double purchased from Anhui Crane pharmaceutcal corporation, Ltd；Glutathione reductase (GR assay kit), glutathione peroxidase (GSH-PX) test It is box, catalase (CAT) testing cassete, total number born (T-SOD) testing cassete, malonaldehyde (MDA) testing cassete, total Protein quantification testing cassete (BCA method) builds up Bioisystech Co., Ltd purchased from Nanjing；Rat A β 1-42 enzyme linked immunosorbent assay (ELISA) Kit is purchased from Elabscience；Deng.

2.3 experimental animal and raising situation

(1) experimental animal

SPF grades of APP/PS1 transgenic mices, male, 6 monthly ages are purchased from Nanjing University-Nanjing biological medicine research institute, move Object production licence number: SCXK (Soviet Union) 2015-0001, quality certification number: 201807065.

(2) rearing conditions

By above-mentioned experimental animal feeding in 25 ± 3 DEG C, the environment of relative humidity 40-70%, animal freely ingests, drinks Water.

2.4 major experimental instruments

The labyrinth Y is purchased from Shanghai Yishu Information Technology Co., Ltd.；Step-through test device, spacious field experimental provision are purchased from Shanghai Yi Shuo Information technology Co., Ltd；Morris water maze is purchased from Jiliang Software Sci-Tech Co., Ltd., Shanghai；The desk-top height of D3024R Fast frozen type centrifuge is purchased from Dragon Laboratory Instruments (Beijing) Co., Ltd.；Deng.

3. experimental method

The setting of 3.1 dosages

13 given the test agent mouse taking dose of table

Grouping	Administered volume	Crude drug dosage	Dosage
				Wild type control group	15ml/kg/d	—	5ml/kg
Transgenic control group	15ml/kg/d	—	5ml/kg
				Donepezil positive drug group	15ml/kg/d	—	1.0mg/kg
Water decoction group	15ml/kg/d	7.50g/kg	7.50g/kg
				QFY low dosage medical fluid group	15ml/kg/d	5.60g/kg	1.40g/kg
QFY middle dosage medical fluid group	15ml/kg/d	11.20g/kg	2.80g/kg
				QFY high dose medical fluid group	15ml/kg/d	30.00g/kg	7.50g/kg

3.2 drugs are prepared

(1) it the high, medium and low dosage group medical fluid of QFY: weighs QFY extract 9.34g and is added containing the water-soluble of 0.5wt%CMC-Na Liquid dissolution, is settled to 25ml, mixes to get QFY high dose medical fluid；12.5ml QFY high dose medical fluid is measured, addition contains The aqueous solution of 0.5wt%CMC-Na is settled to 25ml, mixes to get QFY middle dosage medical fluid；Measure 12.5ml QFY middle dosage medicine Liquid is added the aqueous solution containing 0.5wt%CMC-Na and is settled to 25ml, mixes to get QFY low dosage medical fluid.

(2) QFY-W group medical fluid: water decoction original solution (1g/ml) 12.5ml is measured, two-fold dilution is settled to physiological saline 25ml to get.

(3) positive drug group medical fluid: taking a piece of donepezil piece (content 5mg), 75ml 0.5%CMC-Na dissolution is added, i.e., Obtain positive drug group medical fluid.

3.3 zooperies grouping

Mouse is randomly divided into 7 groups, is respectively: wild type control group, transgenic control group, donepezil positive drug group, QFY high dose group (5.60g/kg), QFY middle dose group (2.80g/kg), QFY low dose group (1.40g/kg), water decoction group (7.50g/kg), every group male mice 12.

APP/PS1 transgenic mice starts slowly to sprout to form senile plaque at the 2-3 monthly age, and when 4 monthly age starts to learn It practises and the variation of the behaviouristics such as memory, obvious senile plaque can be formed in cerebral cortex and hippocampus when 6 monthly age, 12 monthly ages showed The typical senile plaque similar with human patients distribution, mouse are administered when 6 monthly age out.

3.4 medication

Administration route is oral pipe gastric infusion, and administered volume is 15ml/kg weight mouse.

Each group gives following drug: positive drug group: donepezil piece 1.0mg/kg；QFY high dose group: 5.60g/kg, QFY middle dose group: 2.80g/kg, QFY low dose group: 1.40g/kg, water decoction group: 7.50g/kg.Wild type control group and turn Genotype control group gives isometric solvent.

3.5 experimental method

Institute's reagent object is given in stomach-filling to each group mouse respectively, and continuous gavage is administered 3 months, is weighed weekly during administration to adjust Whole dosage.

By Morris water maze laboratory, mouse is recorded in the original platform residence time by computer and passes through original platform Number；Record in maze experiment that mouse is greatly into arm total degree N, spontaneous alternation response rate, mouse leaves peace for the first time in step-through test The time of the whole district and errors number；It is tested by spacious field, the total distance moved in record mouse 5min, in the distance of center lattice movement And residence time etc.；By HE decoration method, α, β, gamma secretase Immunohistochemical Staining, monitors the pathology at brain tissue and become Change；By biochemical detection methods, measure Mice brain tissues A β 1-42 content, and with antioxidant enzyme SOD, GSH-PX, GR and The activity analysis of CAT and the content of Lipid peroxidation index MDA, monitoring response to oxidative stress are horizontal.

4. statistical method

5. experimental result

Influence of the 5.1QFY to APP/PS1 transgenic mice Morris water maze laboratory

Influence (n=10) of 14 QFY of table to APP/PS1 transgenic mice Morris water maze laboratory

Group	The target quadrant residence time (Sec) (means standard deviation)	Wear platform number (means standard deviation)
			Wild type control group	24.09±4.19	2.30±0.42
Transgenic control group	15.03±2.54^#	0.42±0.23^##
			QFY(1.40g/kg)	22.04±3.09	1.30±0.37
QFY(2.80g/kg)	23.78±2.68^*	1.50±0.27
			QFY(5.60g/kg)	24.98±2.21^*	2.30±0.67^*
Water decoction group	20.53±1.85	2.20±0.73
			Positive controls	25.84±3.81^*	2.30±2.30^*

^#P < 0.05,^##P<0.01,^###P < 0.001vs. sham-operation group；^*P<0.05,^**P<0.01,^***P < 0.001vs. model As shown in figure 13, with the increase of training number of days, each group mouse finds the incubation period of platform in the trend shortened to group.With wild type Control group is compared, and transgenic mice shows longer incubation period, shows the damage of its space learning exploring ability.With transgenosis Type control group is compared, and QFY each dosage group incubation period is obviously shortened, and shows that the ability of learning and memory of mouse is improved.

As shown in table 14, the time for passing through target quadrant after the training of transgenic control group mice in 90s compares wild type Mouse is short (P < 0.05), and it is fewer than wild-type mice (P < 0.01) to wear platform number；Compared with transgenic control group, each dose of QFY Amount group significantly extends (2.80g/kg:P < 0.05,5.60g/kg:P < 0.05) in the residence time of target quadrant, and high dose group is small Mouse wears platform number and is significantly increased (5.60g/kg:P < 0.05), the above result shows that, the spatial memory capacity of rat obtains after administration To improvement.

Influence of the 5.2QFY to APP/PS1 transgenic mice Y maze experiment

Influence (n=10) of 15 QFY of table to APP/PS1 transgenic mice Y maze experiment

Group	Spontaneous alternation response rate (%) (means standard deviation)
		Wild type control group	71.56±2.70
Transgenic control group	56.41±4.05^##
		QFY(1.40g/kg)	58.55±3.90
QFY(2.80g/kg)	64.81±2.45^*
		QFY(5.60g/kg)	69.34±2.46^**
Water decoction group	60.33±6.08
		Positive controls	68.84±2.27^**

As shown in Table 15, compared with wild type control group, the spontaneous alternation response rate of transgenic mice is significantly reduced, and is shown The damage (P < 0.01) of its spatial memory capacity.Compared with transgenic control group, the spontaneous alternation response of QFY high, middle dose group Rate dramatically increases (2.80g/kg:P < 0.05,5.60g/kg:P < 0.01), shows that the ability of learning and memory of transgenic mouse obtains To being obviously improved.

Influence of the 5.3QFY to APP/PS1 transgenic mice step-through test

Influence (n=10) of 16 QFY of table to APP/PS1 transgenic mice step-through test

Group	Incubation period (Sec) (means standard deviation)	Errors number (means standard deviation)
			Wild type control group	215.50±28.18	0.60±0.16
Transgenic control group	76.40±27.58^##	2.20±0.42^###
			QFY(1.40g/kg)	164.70±32.06^*	1.20±0.20^**
QFY(2.80g/kg)	193.70±36.81^**	0.80±0.25^***
			QFY(5.60g/kg)	217.20±32.56^**	0.70±0.21^***
Water decoction group	204.90±34.44^**	0.80±0.25^***
			Positive controls	213.80±26.75^**	0.70±0.15^***

As shown in table 16, compared with wild type control group, the incubation period of transgenic mice is obviously shortened (P < 0.01), mistake Number obviously increases (P < 0.001), shows the damage of its ability of learning and memory.Compared with transgenic control group, each dose of QFY Amount group incubation period dramatically increases (1.40g/kg:P < 0.05,2.80g/kg:P < 0.01,5.60g/kg:P < 0.01, water decoction group: P < 0.01), errors number significantly reduces (1.40g/kg:P < 0.01,2.80g/kg:P < 0.001,5.60g/kg:P < 0.001, water Decoction group: P < 0.001), show that the traditional chinese medicine composition of the invention has the ability of learning and memory of transgenic mice and is obviously improved work With.

The influence that 5.4QFY tests APP/PS1 transgenic mice spacious field

Influence (n=10) of 17 QFY of table to APP/PS1 mouse space exploration ability

Group	Total distance (m) (means standard deviation)	The distance (m) (means standard deviation) of middle section
			Wild type control group	12.24±0.98	0.33±0.07
Transgenic control group	6.79±1.03##	0.05±0.03###
			QFY(1.40g/kg)	8.71±1.68	0.08±0.03
QFY(2.80g/kg)	10.13±1.28*	0.17±0.07
			QFY(5.60g/kg)	11.26±11.26**	0.23±0.08*
Water decoction group	10.36±1.15*	0.20±0.06
			Positive controls	11.35±0.87**	0.27±0.05**

#P < 0.05, ##P < 0.01, ###P < 0.001vs. Normal group；*P<0.05,**P<0.01,***P< 0.001vs. model group

As shown in table 17, compared with wild type control group, the movement total distance (P < 0.01) of transgenic mice and in center The move distance (P < 0.001) in region is obviously shortened；Compared with transgenic control group, each dosage group move distance of QFY is significant Increase (2.80g/kg:P < 0.05,5.60g/kg:P < 0.01, water decoction group: P < 0.05), fortune of the high dose group in middle section Dynamic distance also dramatically increases (5.60g/kg:P < 0.05), show transgenic mice space exploration ability be improved significantly.

Influence of the 5.5QFY to A β 1-42 content in APP/PS1 Mice brain tissues

Influence (n=8) of the table 18QFY to A β 1-42 content in APP/PS1 transgenic mouse brain tissue^#P < 0.05,^##P< 0.01,^###P < 0.001vs. sham-operation group；^*P<0.05,^**P<0.01,^***P < 0.001vs. model group

As shown in table 18, compared with wild type control group, the A β 1-42 content of APP/PS1 transgenic mice is obviously increased (P<0.001).Compared with transgenic mouse, the A β 1-42 content of QFY high, middle dose group and water decoction group show conspicuousness It reduces (2.80g/kg:P < 0.01,5.60g/kg:P < 0.001, water decoction group: P < 0.05), shows that QFY can promote A β 1-42's Degradation is transported to outside brain, and the traditional chinese medicine composition of the invention can be relieved the symptom of AD.

Influence of the 5.6QFY to AD rat response to oxidative stress

Influence (n=8) of 19 QFY of table to AD rat model response to oxidative stress

As shown in table 19, compared with wild type control group, the antioxidant enzyme SOD vigor of APP/PS1 transgenic mice, GR vigor, CAT vigor and the equal conspicuousness of GPX vigor reduce (P < 0.001), and MDA content dramatically increases (P < 0.001), shows APP/PS1 transgenic mice shows significant response to oxidative stress.Compared with transgenic control group, SOD vigor is in QFY High, middle dose group and water decoction group show conspicuousness and increase (2.80g/kg:P < 0.05,5.60g/kg:P < 0.01, water decoction Group: P < 0.01)；GR vigor QFY high, middle dose group and water decoction group show conspicuousness increase (2.80g/kg:P < 0.05, 5.60g/kg:P < 0.001, water decoction group: P < 0.01)；CAT vigor shows to show in QFY high, middle dose group and water decoction group Work property increases (2.80g/kg:P < 0.01,5.60g/kg:P < 0.001, water decoction group: P < 0.05)；GPX vigor QFY high, in Dosage group and water decoction group show conspicuousness and increase (2.80g/kg:P < 0.05,5.60g/kg:P < 0.001, water decoction group: P <0.05)；And MDA content each dosage group of QFY and water decoction group show conspicuousness reduce (1.40g/kg:P < 0.05, 2.80g/kg:P < 0.01,5.60g/kg:P < 0.001, water decoction group: P < 0.01).

After result above shows QFY administration, the oxidative stress of APP/PS1 transgenic mice intracerebral is obtained significantly Improve.

5.7HE coloration result

As shown in figure 14, compared with the control group, model group cerebral cortex top, temporal lobe and hippocampus are shown in moderate shallow lake Bloom matter deposition；Compared with model group, positive drug group is shown in that pathological change similar to model group, lesion degree are slight compared with model group Mitigate, QFY group is shown in pathological change similar to model group, the lesion degree mitigation different degrees of compared with model group；QFY various dose Group is compared, high, middle dose group lesion degree is suitable, and lesion degree relatively low-dose group slightly mitigates, water decoction group lesion degree compared with Model group slightly mitigates.

This result of study shows that the traditional chinese medicine composition of the invention can be relieved the symptom of AD.

5.8 α, β, gamma secretase immunohistochemistry

As shown in figures 15-18, for α secretase, compared with normal group, α secretase has no obvious in model group brain tissue It increases；Compared with model group, the equal no difference of science of statistics of α secretase in positive drug group and each dosage group brain tissue of QFY.Such as Figure 18 b Shown, compared with normal group, beta-secretase is significantly raised in model group brain tissue, has significant difference (P < 0.05)；With model group It compares, beta-secretase reduces in positive drug group brain tissue, the different degrees of reduction of beta-secretase in low, middle and high dose groups brain tissue, And there is dosage correlation, and high dose group has extremely significant difference (P < 0.01) compared with model group, water decoction group brain tissue Interior beta-secretase, which has no, to be substantially reduced.As shown in Figure 18 c, compared with normal group, gamma secretase is significantly raised in model group brain tissue (P<0.01)；Compared with model group, gamma secretase is substantially reduced in positive drug group brain tissue, and has extremely significant difference, low, The different degrees of reduction of gamma secretase in middle and high dosage group brain tissue has dosage correlation, middle and high dosage group and model group With significant/extremely significant difference (high dose group: P < 0.01), gamma secretase is substantially reduced in water decoction group brain tissue, and and mould Type group has extremely significant difference (P < 0.01).

This result of study shows that the traditional chinese medicine composition of the invention can be relieved the symptom of Alzheimer disease.

1 Chinese medicine composition of embodiment

2 Chinese medicine composition of embodiment

Composition: ginseng 9g, Semen Ziziphi Spinosae (parched) 4g, Herba Epimedii Preparata 4g, radix rehmanniae preparata 12g, rhizoma atractylodis macrocephalae 8g, 8g parts of RADIX POLYGALAE PREPARATA, rhizoma acori graminei 9g, Radix Angelicae Sinensis 4g, radix glycyrrhizae preparata 1g；

Preparation method: weighing Radix Angelicae Sinensis and rhizoma acori graminei, smashes into coarse granule, and 120g water is added to impregnate 1h, and steam distillation extracts 2h, point Not Shou Ji volatile oil and aqueous extract, betadex and water are added into volatile oil, grinding inclusion obtains inclusion compound, spare, The quality of middle water is 144 times of volatilization oil quality, and the quality of betadex is 12 times of volatilization oil quality；Weigh ginseng, ripe Ground, RADIX POLYGALAE PREPARATA, stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, Semen Ziziphi Spinosae (parched), Herba Epimedii Preparata, radix glycyrrhizae preparata are separately added into the water of 10 times of weight, impregnate 0.5h, decoct It boils 3 times, 1 hour every time, is filtered after merging, obtain extracting solution, it is spare；Merge aqueous extract made from two steps, is concentrated under reduced pressure into 40 The clear cream that relative density is 1.35 at DEG C；Clear cream is dry, dried cream powder is made, the inclusion compound and cyclodextrin is added, mixes, i.e., ?.

3 Chinese medicine composition of embodiment

Composition: ginseng 8g, Semen Ziziphi Spinosae (parched) 4g, Herba Epimedii Preparata 8g, radix rehmanniae preparata 12g, rhizoma atractylodis macrocephalae 8g, 8g parts of RADIX POLYGALAE PREPARATA, rhizoma acori graminei 9g, Radix Angelicae Sinensis 4g, radix glycyrrhizae preparata 2g；

Preparation method: weighing Radix Angelicae Sinensis and rhizoma acori graminei, smashes into coarse granule, and 160g water is added to impregnate 0.5h, and steam distillation is extracted 4h collects volatile oil and aqueous extract respectively, and betadex and water are added into volatile oil, and grinding inclusion obtains inclusion compound, standby With wherein the quality of water is 32 times of volatilization oil quality, and the quality of betadex is 10 times of volatilization oil quality；Weigh people Ginseng, radix rehmanniae preparata, RADIX POLYGALAE PREPARATA, stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, Semen Ziziphi Spinosae (parched), Herba Epimedii Preparata, radix glycyrrhizae preparata are separately added into the water of 8 times of weight, impregnate 1h, It decocts 2 times, 2 hours every time, is filtered after merging, obtain extracting solution, it is spare；Merge aqueous extract made from two steps, is concentrated under reduced pressure into The clear cream that relative density is 1.32 at 60 DEG C；Clear cream is dry, dried cream powder is made, the inclusion compound and cyclodextrin is added, mixes, To obtain the final product.

4 Chinese medicine composition of embodiment

Composition: ginseng 6g, Semen Ziziphi Spinosae (parched) 8g, Herba Epimedii Preparata 6g, radix rehmanniae preparata 9g, rhizoma atractylodis macrocephalae 8g, 4g parts of RADIX POLYGALAE PREPARATA, rhizoma acori graminei 6g, Radix Angelicae Sinensis 9g, radix glycyrrhizae preparata 3g；

Preparation method: taking Radix Angelicae Sinensis and semen ziziphi spinosae, smashes, and decocts twice, adds water to cook twice, adds 150g water for the first time, impregnates 0.5h, decocts 50min, and second plus 100g water decoct 30min.Decoction liquor sieves with 100 mesh sieve, filtering, merging filtrate, at 55 DEG C Be concentrated in vacuo to every 1ml concentrate crude drug amount containing 1g to get.

5 Chinese medicine composition of embodiment

Preparation method: taking Radix Angelicae Sinensis and semen ziziphi spinosae, smashes, and decocts twice, adds water to cook twice, adds 100g water for the first time, impregnates 1h, 30min is decocted, second plus 80g water decoct 20min.Decoction liquor crosses 120 meshes, filtering, merging filtrate, and vacuum is dense at 55 DEG C Be reduced to every 1ml concentrate crude drug amount containing 2g to get.

6 Chinese medicine composition of embodiment

Preparation method: taking Radix Angelicae Sinensis and semen ziziphi spinosae, smashes, and decocts twice, adds water to cook twice, adds 120g water for the first time, impregnates 0.5h, decocts 30min, and second plus 90g water decoct 20min.Decoction liquor crosses 120 meshes, filtering, merging filtrate, true at 55 DEG C Sky be concentrated into every 1ml concentrate crude drug amount containing 1g to get.

7 Chinese medicine composition of embodiment

8 Chinese medicine composition of embodiment

Composition: ginseng 9g, Semen Ziziphi Spinosae (parched) 4g, Herba Epimedii Preparata 4g, radix rehmanniae preparata 12g, rhizoma atractylodis macrocephalae 8g, 8g parts of RADIX POLYGALAE PREPARATA, rhizoma acori graminei 9g, Radix Angelicae Sinensis 4g, radix glycyrrhizae preparata 1g.

9 Chinese medicine composition of embodiment

Preparation method: the composition of proportion described in Example 8-10 adds 50% EtOH Sonicate to extract twice, adds 120g for the first time Ethyl alcohol, ultrasonic 30min, second plus 90g ethyl alcohol, ultrasonic 20min.Filtering, merging filtrate, at 55 DEG C vacuum concentration to get.

10 spray of embodiment

Chinese medicine composition is made by any preparation method of claim 1-9 in the bulk pharmaceutical chemicals for taking any composition of claim 1-9, Customary adjuvant is added, spray is made through common process.

11 Wet-dressing agent of embodiment

Chinese medicine composition is made by any preparation method of claim 1-9 in the bulk pharmaceutical chemicals for taking any composition of claim 1-9, Customary adjuvant is added, Wet-dressing agent is made through common process.

12 granule of embodiment

Preparation method: taking bulk pharmaceutical chemicals, adds 12 times of water rettings to extract 2 times, 10 hours every time, combined extract filtered, and concentration is dense Contracting liquid is dried under reduced pressure, and smashes into fine powder, customary adjuvant is added, mix, granule is made.

13 tablet of embodiment

Preparation method: taking bulk pharmaceutical chemicals, adds 50% EtOH Sonicate to extract 2 times, 1 hour every time, combined extract filtered, and concentration is dense Contracting liquid is dried under reduced pressure, and smashes into fine powder, customary adjuvant is added, mix, tablet is made in direct powder compression.

14 capsule of embodiment

Composition: ginseng extract 6g, Wild jujube seeds extract 6g, Shorthorned Epimedium P.E 6g, radix rehmanniae preparata extract 9g, Rhizoma Atractylodis Macrocephalae extract Object 5g, 5g parts of Cortex et Radix Polygalae (processed) extract, Rhizoma Acori Graminei extract 6g, angelica extract 9g, licorice 3g；

Preparation method: the extract is respectively the extract that each bulk pharmaceutical chemicals extract preparation through 60% alcohol reflux, is mentioned above-mentioned It at fine powder after taking object to be dried under reduced pressure, mixes, is packed into capsule, capsule is made.

15 ointment of embodiment

Preparation method: the extract is respectively the extract that each bulk pharmaceutical chemicals extract preparation through 60% alcohol reflux, is mentioned above-mentioned It takes object that customary adjuvant is added, mixes, ointment is made.

16 oral solution of embodiment

Preparation method: taking Radix Angelicae Sinensis and semen ziziphi spinosae, smashes, and decocts twice, adds water to cook twice, adds 120g water for the first time, impregnates 0.5h, decocts 30min, and second plus 90g water decoct 20min.Decoction liquor crosses 120 meshes, filtering, filtrate constant volume, and packing is gone out Bacterium obtains oral solution.

Obviously, the above embodiments are merely examples for clarifying the description, and does not limit the embodiments.It is right For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of variation or It changes.There is no necessity and possibility to exhaust all the enbodiments.And it is extended from this it is obvious variation or It changes still within the protection scope of the invention.

Claims

1. a kind of Chinese medicine composition, which is characterized in that the bulk pharmaceutical chemicals including following parts by weight: 2-15 parts of ginseng, Semen Ziziphi Spinosae (parched) 2- 15 parts, 2-15 parts of Herba Epimedii Preparata, 3-18 parts of Rehmannia glutinosa, 1-12 parts of RADIX POLYGALAE PREPARATA, 1-12 parts of stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, 3-18 parts of Radix Angelicae Sinensis, stone Chang 2-15 parts of Pu, 1-10 parts of radix glycyrrhizae preparata.

2. Chinese medicine composition according to claim 1, which is characterized in that the bulk pharmaceutical chemicals including following parts by weight: ginseng 4-9 Part, 4-9 parts of Semen Ziziphi Spinosae (parched), 4-9 parts of Herba Epimedii Preparata, 5-12 parts of Rehmannia glutinosa, 3-8 parts of RADIX POLYGALAE PREPARATA, 3-8 parts of stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, Radix Angelicae Sinensis 5- 12 parts, 4-9 parts of rhizoma acori graminei, 1-5 parts of radix glycyrrhizae preparata.

3. Chinese medicine composition according to claim 1 or 2, which is characterized in that institute's Chinese medicine composition is each bulk pharmaceutical chemicals through powder Essence obtains composition；Or routinely extracting method or the extraction that routinely extracting method is extracted respectively after each bulk pharmaceutical chemicals mixing Object；Or extract passes through the live part that polishing purification technique obtains.

4. Chinese medicine composition according to claim 1 to 3, which is characterized in that the general extraction methods include leaching One or more of stain extraction, decoction extraction, refluxing extraction, seepage pressure effects, ultrasonic extraction and steam distillation；Extraction solvent Including water or 20-95vt% ethanol solution；The polishing purification technique include water extract-alcohol precipitation, extraction, silica gel chromatograph post separation and One or more of macroreticular resin post separation.

5. a kind of method for preparing any Chinese medicine composition in claim 1-4, which is characterized in that including walking as follows It is rapid:

(1) Radix Angelicae Sinensis and rhizoma acori graminei, extracting in water are weighed, steam distillation is extracted, and volatile oil and aqueous extract is obtained, into volatile oil Betadex and water inclusion is added, obtains inclusion compound；

(2) ginseng, radix rehmanniae preparata, RADIX POLYGALAE PREPARATA, stir-baked RHIZOMA ATRACTYLDIS MACROCEPHALAE in bran, Semen Ziziphi Spinosae (parched), Herba Epimedii Preparata and radix glycyrrhizae preparata are weighed, extracting in water obtains water Extracting solution；

6. the preparation method of Chinese medicine composition according to claim 5, which is characterized in that

In step (1) extraction process, Radix Angelicae Sinensis and rhizoma acori graminei are taken, is smashed, the water for accounting for 8-12 times of Radix Angelicae Sinensis and rhizoma acori graminei total weight is added, 0.3-1h is impregnated, steam distillation extracts volatile oil, and extraction time 2-8h obtains volatile oil and aqueous extract；

7. the preparation method of Chinese medicine composition according to claim 5 or 6, which is characterized in that step (1) includes process In, betadex and water are added in the volatile oil, grinding inclusion 20-40min is stood, and inclusion compound, 30- are collected in filtering 50 DEG C of drying, it is spare；

8. a kind of pharmaceutical preparation, which is characterized in that wanted using any Chinese medicine composition in claim 1-4 or right Seeking Chinese medicine composition made from any preparation method in 5-7 is that customary adjuvant is added according to common process system in active component It is standby to obtain.

9. pharmaceutical preparation according to claim 8, which is characterized in that the pharmaceutical preparation be ointment, patch, liniment, Lotion, solution, injection, spray, syrup, Wet-dressing agent, suppository, tablet, pill, granule or capsule.

10. preparation described in any one of Chinese medicine composition of any of claims 1-4 or claim 5-7 Chinese medicine composition made from method or the pharmaceutical preparation in claim 8 or 9 treat the drug of Alzheimer disease in preparation In application.