CN105395643A - Rose-angelica sinensis composition for treating Alzheimer's disease and application thereof - Google Patents

Rose-angelica sinensis composition for treating Alzheimer's disease and application thereof Download PDF

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CN105395643A
CN105395643A CN201510937743.6A CN201510937743A CN105395643A CN 105395643 A CN105395643 A CN 105395643A CN 201510937743 A CN201510937743 A CN 201510937743A CN 105395643 A CN105395643 A CN 105395643A
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radix angelicae
angelicae sinensis
flos rosae
rosae rugosae
disease
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CN105395643B (en
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不公告发明人
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Gansu Oriential Tianren Rose Technology Development Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/73Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/738Rosa (rose)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
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  • Epidemiology (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Medicines Containing Plant Substances (AREA)

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and in particular, relates to a rose-angelica sinensis composition for treating Alzheimer's disease and an application thereof. The composition contains rose flowers and angelica sinensis. The rose-angelica sinensis composition has a significant therapeutic effect on a caenorhabditis elegans Alzheimer's disease pathology model, can be applied in preparation of drugs for treatment of Alzheimer's disease, and also can be applied in preparation of related health products for prevention and adjuvant treatment of Alzheimer's disease.

Description

A kind of Flos Rosae Rugosae Radix Angelicae Sinensis compositions and application thereof for the treatment of Alzheimer's disease
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of Flos Rosae Rugosae Radix Angelicae Sinensis compositions and application thereof for the treatment of Alzheimer's disease.
Background technology
Alzheimer's disease (Alzheimer'sMdisease, AD), being a kind of based on the nervous system degenerative disease of Progressive symmetric erythrokeratodermia cognitive disorder and memory impairment, is the modal a kind of form of senile dementia.Feature is shown as clinically with dysmnesia, aphasia, agnosia, the infringement of visual space technical ability, n-back test obstacle and the generalized dementia such as personality and behavior change.In dementia patients, proportion is more than 75%.Along with the aggravation of China's aging degree, AD can become one of principal disease affecting senior health and fitness, and effective prevention and therapy AD becomes the another key subjects of pendulum in face of us.
Amyloid beta deposition (aβ protein) and neurofibrillary tangles are the two large key pathological feature of AD.Modern medicine has carried out years of researches to the pathogenesis of AD, but due to its cause of disease complexity, the pathogenesis of this disease is still indefinite so far, and " A β cascade hypothesis " is current by one of well accepted mechanism of scientific circles.This theory thinks that the A β of abnormal deposition in brain in patients is by a series of cascade reactions such as radical reaction, Mitochondrial oxidative damage and inflammatory reactions; directly or indirect action in neuron and neurogliocyte; finally cause neuronal function abnormal or dead; cause cognitive impairment and amnesia, finally cause dementia.In familial Alzheimer disease disease patient, find that amyloid precursor protein (APP) gene and presenilin genes are undergone mutation, cause A β to become this theory evidence the strongest in the overexpression of brain.Therefore amyloid beta has become the generally acknowledged anti-AD drug targets of screening.
The AD cause of disease is complicated, the course of disease is very long and morbidity link is more, need Long-term taking medicine, anti-Alzheimer disease medicine acetylcholinesteraseinhibitors inhibitors (as galantamine) main at present and N-methyl-D-aspartate receptor (nmda receptor) antagonist (as memantine), but said medicine is expensive, hallucination after taking medicine, misunderstanding, dizziness, headache and the side effect such as tired are remarkable, and can only delay, but can not control or reverse conditions of patients.
And Chinese medicine composition has the feature of various active component, Mutiple Targets, can overcome the weak point of Western medicine to a certain extent, the drug candidates making screening from Chinese medicine composition treasure-house be used for the treatment of AD has a extensive future.
Flos Rosae Rugosae is the Chinese medicine of promoting flow of QI and blood simply, Flos Rosae Rugosae chloroform extract is proved to be the rat embryonic neuronal cell axon growth that can promote In vitro culture, and the neuron axon atrophy (Awaleetal., 2011) suppressing A β (25-35) to cause.But still do not know whether rose water decoct has anti-AD effect.Radix Angelicae Sinensis sweet in the mouth, pungent, micro-hardship, warm in nature; Return liver, the heart, spleen channel; Fragrant strongly fragrant row falls apart, and can rise and can fall; Have and enrich blood, invigorate blood circulation, the effect of menstruction regulating and pain relieving.Theory of Chinese medical science is thought when the product being classified as tune blood of enriching blood, and is gynecological's common medicine.
Caenorhabditis elegans (Caenorhabditiselegans) is the research platform of a very useful multifunctional drug screening and mechanism of drug action.Its is cheap, easily cultivate; Generation cycle is short, offspring's number is many, can obtain the consistent individuality of a large amount of background simultaneously, ensures experimental repeatability and adopts large sample amount to test, thus get rid of the impact of individual variation; With higher organism high conservative (KalettaandHengartner, 2006) in gene and molecular pathway.It from the bridge being sieved to horizontal medicine in Mice Body at the beginning of the horizontal medicine of cells in vitro and sieving again, is more and more subject to the favor of pharmacy man as one.The arrhythmia medicine that devGen company of the U.S. utilizes humanization nematicide to screen is entered clinical research by FDA approval.
The foundation of humanization Caenorhabditis elegans AD pathological model people source A β 1-42 gene is proceeded to Myosin promoter downstream and reaches by temperature control table, this nematicide strain can at 15 DEG C of normal growths, under being transferred to 25 DEG C of conditions, A β 1-42 expresses and accumulates at its intramuscular, causes nematicide lose motor capacity and benumb.Add test medicine and can delay muscular paralysis phenotype, the percentage ratio that its result accounts for tested nematode population quantity with muscular paralysis nematode population represents.Do not benumb nematicide ratio higher, medicine anti-AD effect is more remarkable.This model is used to anti-AD disease mechanism and anti-AD medicine and material standed for study on mechanism (Link, 1995 already; 2001).
Based on above-mentioned present Research, the invention provides a kind of Flos Rosae Rugosae Radix Angelicae Sinensis compositions for the treatment of Alzheimer's disease, this Flos Rosae Rugosae Radix Angelicae Sinensis compositions plays the anti-AD of synergism.The present invention provides the application of this Flos Rosae Rugosae Radix Angelicae Sinensis compositions simultaneously.
List of references
KalettaT,HengartnerMO.Findingfunctioninnoveltargets:C.elegansasamodelorganism.NatRevDrugDiscov2006,5:387e398.
LinkCD.Expressionofhumanbeta-amyloidpeptideintransgenicCaenorhabditiselegans.ProcNatlAcadSciUSA1995,92:9368e9372.
LinkCD.Transgenicinvertebratemodelsofage-associatedneurodegenerativediseases.MechAgeingDev2001,122:1639e1649.
AwaleS,TohdaC,TezukaTetal.ProtectiveEffectsofRosadamascenaanditsactiveconstituentonAβ(25–35)-inducedneuriticatrophy.Evidence-BasedComplementaryandAlternativeMedicine2011,doi:10.1093/ecam/nep149.
Summary of the invention
The object of the invention is to provide a kind of Flos Rosae Rugosae Radix Angelicae Sinensis compositions for the treatment of Alzheimer's disease, and said composition has the potentiality for the treatment of Alzheimer's disease.
Another object of the present invention is to provide the application of above-mentioned Flos Rosae Rugosae Radix Angelicae Sinensis compositions.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
Treat a Flos Rosae Rugosae Radix Angelicae Sinensis compositions for Alzheimer's disease, described compositions contains Flos Rosae Rugosae, Radix Angelicae Sinensis.
Treat a Flos Rosae Rugosae Radix Angelicae Sinensis compositions for Alzheimer's disease, described compositions contains the crude drug of following weight ratio: Flos Rosae Rugosae 2-4 part, Radix Angelicae Sinensis 12 parts.
Described Flos Rosae Rugosae Radix Angelicae Sinensis compositions can be applied in the medicine of preparation treatment Alzheimer's disease.
Described Flos Rosae Rugosae Radix Angelicae Sinensis compositions is capsule, tablet, granule, powder, oral liquid, pill as the pharmaceutical preparation of active ingredient.
Described Flos Rosae Rugosae Radix Angelicae Sinensis compositions can be applied in the health product preparing prevention and auxiliary treatment Alzheimer's disease.
Described Flos Rosae Rugosae Radix Angelicae Sinensis compositions is capsule, tablet, granule, powder, oral liquid, pill as the health product dosage form of effective ingredient.
Beneficial effect of the present invention:
1, the present invention tests with Caenorhabditis elegans AD pathological model, and result shows: this Flos Rosae Rugosae Radix Angelicae Sinensis compositions has significant therapeutic effect to Caenorhabditis elegans AD pathological model tool.Significantly can delay the paralysis phenotype of Caenorhabditis elegans AD pathological model, this Flos Rosae Rugosae Radix Angelicae Sinensis compositions is pointed out to have the potentiality for the treatment of Alzheimer's disease, can apply in the medicine of preparation treatment Alzheimer's disease, also can apply in the health product preparing prevention and auxiliary treatment Alzheimer's disease.
2, when Flos Rosae Rugosae and Radix Angelicae Sinensis alone time, under concentration of the present invention, all not there is therapeutical effect to Caenorhabditis elegans AD pathological model, but then there is when the two combinationally uses remarkable anti-AD effect, therefore, in Flos Rosae Rugosae Radix Angelicae Sinensis compositions provided by the invention, Flos Rosae Rugosae and Radix Angelicae Sinensis play the anti-AD of synergism.
Below in conjunction with specific embodiment, technical scheme of the present invention is described in further detail, but protection scope of the present invention is not limited to the following stated.
Accompanying drawing explanation
Fig. 1 Flos Rosae Rugosae and Radix Angelicae Sinensis play the muscular paralysis that synergism delays AD Caenorhabditis elegans
Control-blank group, R50-rose wate decocting liquid low concentration group, R25-rose wate decocting liquid high concentration group; D50-water decoction of Angelica sinensis low concentration group, D25-water decoction of Angelica sinensis high concentration group; D25+R50-Flos Rosae Rugosae Radix Angelicae Sinensis compositions low concentration group, concentration group in D25+R25-Flos Rosae Rugosae Radix Angelicae Sinensis compositions.
Fig. 2 Flos Rosae Rugosae Radix Angelicae Sinensis composition dosage relies on the muscular paralysis that ground delays AD Caenorhabditis elegans
Control-blank group, concentration group in D25+R25-Flos Rosae Rugosae Radix Angelicae Sinensis compositions, D12.5+R12.5-Flos Rosae Rugosae Radix Angelicae Sinensis compositions high concentration group.
Detailed description of the invention
The preparation method of embodiment 1 Flos Rosae Rugosae Radix Angelicae Sinensis compositions
Take Flos Rosae Rugosae 2g, Radix Angelicae Sinensis 12g, add water 400mL, and heated and boiled also keeps 30 minutes, is settled to 200mL, filtration sterilization, for subsequent use.
Take Flos Rosae Rugosae 4g, Radix Angelicae Sinensis 12g, add water 400mL, and heated and boiled also keeps 30 minutes, is settled to 200mL, filtration sterilization, for subsequent use.
Embodiment 2 Flos Rosae Rugosae and Radix Angelicae Sinensis play the muscular paralysis that synergism delays AD Caenorhabditis elegans
1. biomaterial
(1) Caenorhabditis elegans CL4176 is purchased from CaenorhabditisGeneticsCenter (CGC); For transgenic strain, express mankind A β at 25 DEG C of temperature-induced lower muscle specifics 1-42, A β 1-42assemble in muscular tissue, finally cause nematicide to be benumbed, the present embodiment adopts C. Elegans Automatic Screening CL4176 strain as the pathological model of the anti-AD medicine of screening.
(2) escherichia coli OP50 (uracil leaky mutant), purchased from CaenorhabditisGeneticsCenter (CGC), as the food of Caenorhabditis elegans.
2. reagent
(1) solid NGM (NematodeGrowthMedium) medium component and making (being upgraded to example with 1):
Composition Content
NaCl 3.00g
K 2HPO 4 2.34g
KH 2PO 4 17.23g
Peptone 2.50g
Agar 17.00g
Supplement H 2O extremely 1000mL
After solid NGM culture medium prepares, high-pressure constant temp sterilizing 20min at 121 DEG C, adds 5mg/mL cholesterol 1mL, 1MMgSO under aseptic operating platform 41mL, 1MCaCl 21mL shakes up, and pours sterilized 9cm culture plate while hot into, about 20mL/ plate.Leave standstill and wait for culture medium solidifying, for subsequent use.
(2) M9 formula of liquid
Composition Content
Na 2HPO 4 6.00g
KH 2PO 4 3.00g
NaCl 5.00g
1M MgSO 4 1.00mL
Supplement H 2O extremely 1000mL
(3) preparation of lysate: 6.4%NaClO solution and 1MNaOH solution 1:1 mixing by volume.
3. the NGM of preparation containing rose wate decocting liquid is dull and stereotyped
The preparation of rose wate decocting liquid:
Flos Rosae Rugosae 4g, add water 400mL, and heated and boiled also keeps 30 minutes, is settled to 200mL, filtration sterilization, for subsequent use, and rose wate decocting liquid concentration conversion dose of making a living is 20mg/mL.
The preparation of water decoction of Angelica sinensis:
Radix Angelicae Sinensis 12g, add water 400mL, and heated and boiled also keeps 30 minutes, is settled to 200mL, filtration sterilization, for subsequent use, and water decoction of Angelica sinensis concentration conversion dose of making a living is 60mg/mL.
The NGM of configuration containing decocting liquid is dull and stereotyped:
Get rose wate decocting liquid, add in NGM culture medium, making the final concentration of rose wate decocting liquid in pastille NGM culture dish be scaled crude drug amount is 0.4mg/mL and 0.8mg/mL; Making the final concentration of water decoction of Angelica sinensis in pastille NGM culture dish be scaled crude drug amount is 1.2mg/mL and 2.4mg/mL; Making in pastille NGM culture dish when the final concentration of Flos Rosae Rugosae Radix Angelicae Sinensis compositions decocting liquid is scaled crude drug amount is 2.8mg/mL and 3.2mg/mL.Leave standstill and wait for culture medium solidifying.In culture medium, even spread escherichia coli OP50 is as the food of nematicide.
4. implementation step
(1) cultivation of nematicide:
Be connected on by nematicide and scribble on the solid NGM plate of escherichia coli OP50, the incubator being then placed in 16 DEG C is cultivated, and carries out synchronization process when nematicide grows to adult.
(2) nematicide synchronization:
Select containing a large amount of adult and the NGM culture medium having partial line worm's ovum to hatch, with M9 liquid, nematicide is swept away from culture medium, transfer in centrifuge tube, leave standstill and make, at the bottom of nematicide free settling to pipe, to abandon supernatant.How many sight line worm amounts adds lysate in centrifuge tube, whirlpool misfortune agitator vibrates 5-7 minute until nematicide complete rupture time stop vortex, and be sub-packed in 1.5mL centrifuge tube, wash line eggs three times with M9 solution.
(3) experimental group is arranged
Blank group (Control): sterilized water.
Rose wate decocting liquid low concentration group (R50): in the NGM plate of pastille, the final concentration of rose wate decocting liquid is 0.4mg/mL;
Rose wate decocting liquid high concentration group (R25): in the NGM plate of pastille, the final concentration of rose wate decocting liquid is 0.8mg/mL;
Water decoction of Angelica sinensis low concentration group (D50): in the NGM plate of pastille, the final concentration of water decoction of Angelica sinensis is 1.2mg/mL;
Water decoction of Angelica sinensis high concentration group (D25): in the NGM plate of pastille, the final concentration of water decoction of Angelica sinensis is 2.4mg/mL;
Flos Rosae Rugosae Radix Angelicae Sinensis compositions low concentration group (D25+R50): in the NGM plate of pastille, the final concentration of Flos Rosae Rugosae Radix Angelicae Sinensis compositions is 2.8mg/mL;
Concentration group (D25+R25) in Flos Rosae Rugosae Radix Angelicae Sinensis compositions: in the NGM plate of pastille, the final concentration of Flos Rosae Rugosae Radix Angelicae Sinensis compositions is 3.2mg/mL;
(4) experimental procedure
The line eggs be sub-packed in after synchronization in centrifuge tube is transferred to and is coated with OP50 and mixes in the NGM culture dish of the rose wate decocting liquid of variable concentrations, blank group is be coated with OP50 and be added with the NGM culture dish with the isopyknic sterilized water of rose wate decocting liquid, each culture dish 60 nematicides, each drug level three culture dishs, as parallel, cultivate 3 days to the L3 phase for 16 DEG C.Wherein, in pastille NGM culture dish, final concentration such as the experimental group of each group is arranged.
In order to make nematicide express A β, L3 phase nematicide being turned and induces at 25 DEG C, start after 34h to count nematicide paralysis number.Every two hours count once, until all nematicides are all benumbed (when paralysis refers to mechanical stimulus nematode body, nematicide can not move or only have head movement).The results are shown in Figure 1.
(5) experimental result
The vertical coordinate of Fig. 1 represents the percentage ratio that accounts for of Caenorhabditis elegans not having to benumb, and at point at the same time, this value is larger, shows not have the Caenorhabditis elegans ratio of paralysis in this processed group larger, and namely to delay the effect of paralysis stronger for medicine.
Experimental result shows, in the present embodiment alone Flos Rosae Rugosae or Radix Angelicae Sinensis, does not show the retarding action to AD nematicide muscular paralysis.After by the two Combination application, show, to AD nematicide muscular paralysis, there is significant retarding action.This shows that Flos Rosae Rugosae and Radix Angelicae Sinensis can play the anti-AD of synergism.
Embodiment 3 Flos Rosae Rugosae Radix Angelicae Sinensis composition dosage relies on the muscular paralysis that ground delays AD Caenorhabditis elegans
(1) experimental group is arranged
Blank group (Control): sterilized water.
Concentration group (D25+R25) in Flos Rosae Rugosae Radix Angelicae Sinensis compositions: in the NGM plate of pastille, the final concentration of Flos Rosae Rugosae Radix Angelicae Sinensis compositions is scaled crude drug amount is 3.2mg/mL;
Flos Rosae Rugosae Radix Angelicae Sinensis compositions high concentration group (D12.5+R12.5): in the NGM plate of pastille, the final concentration of Flos Rosae Rugosae Radix Angelicae Sinensis compositions is scaled crude drug amount is 6.4mg/mL;
(2) other laboratory operating procedures is with embodiment 2.
(3) experimental result
The vertical coordinate of Fig. 2 represents the percentage ratio that accounts for of Caenorhabditis elegans not having to benumb, and at point at the same time, this value is larger, shows not have the Caenorhabditis elegans ratio of paralysis in this processed group larger, and namely to delay the effect of paralysis stronger for medicine.
Experimental result shows, Flos Rosae Rugosae Radix Angelicae Sinensis composition dosage relies on the muscular paralysis that ground delays AD Caenorhabditis elegans.
Proved by above embodiment, Flos Rosae Rugosae Radix Angelicae Sinensis compositions provided by the invention plays significant synergistic therapeutic action to Caenorhabditis elegans AD pathological model, Flos Rosae Rugosae Radix Angelicae Sinensis compositions provided by the invention is pointed out to have treatment Alzheimer's disease potentiality, can apply in the medicine of preparation treatment Alzheimer's disease, also can apply in the health product of preparation prevention Alzheimer's disease.

Claims (6)

1. treat a Flos Rosae Rugosae Radix Angelicae Sinensis compositions for Alzheimer's disease, it is characterized in that, described compositions contains Flos Rosae Rugosae, Radix Angelicae Sinensis.
2. a kind of Flos Rosae Rugosae Radix Angelicae Sinensis compositions for the treatment of Alzheimer's disease as claimed in claim 1, it is characterized in that, described compositions contains the crude drug of following weight ratio: Flos Rosae Rugosae 2-4 part, Radix Angelicae Sinensis 12 parts.
3. the application of the Flos Rosae Rugosae Radix Angelicae Sinensis compositions as described in any one of claim 1-2 in the medicine of preparation treatment Alzheimer's disease.
4. apply as claimed in claim 3, it is characterized in that, described Flos Rosae Rugosae Radix Angelicae Sinensis compositions is capsule, tablet, granule, powder, oral liquid, pill as the pharmaceutical preparation of active ingredient.
5. the application of the Flos Rosae Rugosae Radix Angelicae Sinensis compositions as described in any one of claim 1-2 in the health product preparing prevention and auxiliary treatment Alzheimer's disease.
6. apply as claimed in claim 5, it is characterized in that, described Flos Rosae Rugosae Radix Angelicae Sinensis compositions is capsule, tablet, granule, powder, oral liquid, pill as the health product dosage form of effective ingredient.
CN201510937743.6A 2015-12-16 2015-12-16 A kind of rose Radix Angelicae Sinensis composition for treating Alzheimer's disease and its application Active CN105395643B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101912597A (en) * 2010-08-27 2010-12-15 葛德钜 Medicament for treating senile dementia and preparation method thereof
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CN104474429A (en) * 2014-12-30 2015-04-01 兰州古驰生物科技有限公司 Traditional Chinese medicine preparation with function of reducing hypomnesis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101912597A (en) * 2010-08-27 2010-12-15 葛德钜 Medicament for treating senile dementia and preparation method thereof
CN103446317A (en) * 2012-05-30 2013-12-18 王雪丽 Traditional Chinese medicine for curing senile dementia
CN104474429A (en) * 2014-12-30 2015-04-01 兰州古驰生物科技有限公司 Traditional Chinese medicine preparation with function of reducing hypomnesis

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Title
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