CN108310234A - A kind of pharmaceutical composition for treating cognition dysfunction and preparation method thereof, preparation and application - Google Patents

A kind of pharmaceutical composition for treating cognition dysfunction and preparation method thereof, preparation and application Download PDF

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CN108310234A
CN108310234A CN201810319913.8A CN201810319913A CN108310234A CN 108310234 A CN108310234 A CN 108310234A CN 201810319913 A CN201810319913 A CN 201810319913A CN 108310234 A CN108310234 A CN 108310234A
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pharmaceutical composition
preparation
disease
grass
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周荣光
赵加强
曾跃勤
顾静波
周新富
郭泽剑
文冰亭
刘丹
刘一丹
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KPC Pharmaceuticals Inc
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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)
    • A61K36/25Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
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    • A61K36/07Basidiomycota, e.g. Cryptococcus
    • A61K36/076Poria
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    • 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)
    • A61K36/69Polygalaceae (Milkwort family)
    • 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)
    • A61K36/88Liliopsida (monocotyledons)
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/898Orchidaceae (Orchid family)
    • A61K36/8988Gastrodia
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
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    • AHUMAN NECESSITIES
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    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

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Abstract

The invention discloses a kind of pharmaceutical composition for treating cognition dysfunction and preparation method thereof, preparation and applications.Pharmaceutical composition of the present invention is made of 10 ~ 90 parts of the Radix Notoginseng of parts by weight, 10 ~ 90 parts of Poria cocos, 5 ~ 60 parts of Radix Polygalae, 5 ~ 60 parts of grass-leaved sweetflag, 2 ~ 40 parts of Rhizoma Gastrodiae, has good therapeutic effect to Alzheimer's disease, vascular dementia and mild cognition impairment.Medicament composing prescription essence of the present invention is small, significant in efficacy, safe and non-toxic, plays the role for the treatment of both manifestation and root cause of disease to cognition dysfunction disease, is especially suitable for person in middle and old age and slow disease patient uses, have high clinical value, wide market.

Description

A kind of pharmaceutical composition for treating cognition dysfunction and preparation method thereof, preparation with Using
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of pharmaceutical composition and its system for treating cognition dysfunction Preparation Method, preparation and application.
Background technology
Cognition dysfunction refers to human body due to the role and influence by factors such as wound, disease or heredity, normal development Brain damage or exception, lead to decline or the abnormal degeneration of the cognitive functions such as language, study, memory, thinking and intelligence. Cognition dysfunction disease is divided by severity, mainly there is mild cognition impairment(mild cognitive Impairment, MCI)With dull-witted two classes, wherein it is (i.e. old silly that dementia can substantially be divided into Alzheimer's disease according to the cause of disease It is slow-witted, Alzheimer'sdisease, AD), blood vessel nature feeble-mindedness (Vascular Dementia, VaD) and other neurological diseases or For example postoperative dementia of dementia caused by systemic disease, diabetes dementia etc..With the aggravation of China's aging degree, cognitive function Obstacle has become the important health problem that China human mortality especially old group population faces, it not only influences people's Quality of life, returns family and society brings white elephant.
Alzheimer's disease(AD), also known as senile dementia is a kind of principal disease in cognition dysfunction, morbidity At present in trend is steeply risen, the death rate is only second to heart disease, tumour and apoplexy and occupies the 4th rate.Alzheimer's disease is It is happened at a kind of chronic progressive degeneration brain degenerative disease of Senectitude and presenium, with progressive hypomnesia, cognition Obstacle, personality change are main feature.Be divided into Familial Occurrence and two kinds sporadic, and Familial Occurrence senile dementia be divided into for Early onset and late hair style.The pathological change of Alzheimer's disease is morphologically mainly shown as the apparent atrophy of cerebral cortex, with volume Leaf, temporal lobe, based on top.Convolutional atrophy narrows, and brain ditch is broadening, and the ventricles of the brain expand.Its main changes in histopathology is big Occur assembling the amyloid plaques formed by the hypotype (i.e. A β 42) of 42 amino acid peptides of beta-amyloid protein outside brain cell (senile plaque, SP), and the nerve fibre for occurring being made of the Tau albumen of cellular microtubules and Hyperphosphorylationof in neuron twine Knot(NFT).
Vascular dementia (VaD) is the another kind of principal disease in cognition dysfunction, and incidence also rises year by year, 65 years old The illness rate of above crowd's medium vessels dementia is about 5%.Vascular dementia is due to brains such as cerebral ischemia, cerebral hemorrhage, cerebral infarctions One based on the higher nerve cognition dysfunction group Comprehensive Clinical generated on the basis of brain tissue damage caused by vascular diseases Sign includes mainly multi-infarct dementia, multiple lacunar is dull-witted, cerebral amyloid angiopathy becomes, brain Low perfusion is dull-witted and Hemorrhagic dementia etc..
Currently, in the market treat cognition dysfunction drug, mainly have Doneppezil Hydrochloride (Aricept Aricept), Rivastigmine-hydrogentartrate (Exelon Exelon), huperzine (Huperzine A-Zhulin Antun Huperzine), galanthamine ( Galantamine) anticholinesterases (cholinesterase inhibitors, ChEIs) and the calcium channel blocker such as (Such as Nimodipine Nimodipine, hydergine Hydergine), brain cell activation agent(Such as Cerebrolysin Cerebrolysin)Deng. Although these drugs can improve or mitigate to a certain extent the partial symptoms of patient, the development of disease cannot be prevented, is existed The problems such as action target spot is single, weak curative effect, and effect is not lasting, and toxic side effect is big, patient's poor resistance.Chinese medicine has multiple target point, The features such as treating both manifestation and root cause of disease, toxic side effect is small, therefore the Chinese medicine for developing safe and efficient treatment cognition dysfunction disease has very Important meaning.
Invention content
The first object of the present invention is to provide a kind of pharmaceutical composition for treating cognition dysfunction;Second purpose is The preparation method of the pharmaceutical composition is provided;Third is designed to provide the preparation of the pharmaceutical composition;4th mesh Be the application of the pharmaceutical composition is provided.
The first object of the present invention is achieved in that the pharmaceutical composition of the treatment cognition dysfunction by weight 2 ~ 40 parts of 10 ~ 90 parts of the Radix Notoginseng of part, 10 ~ 90 parts of Poria cocos, 5 ~ 60 parts of Radix Polygalae, 5 ~ 60 parts of grass-leaved sweetflag and Rhizoma Gastrodiae compositions.
In the present invention, Radix Notoginseng is panax araliaceae plantPanax notoginseng Burk.F. the drying of H. Chen Root.Excavation, cleaning, drying before autumn, the flowers are in blossom.This product is sweet in flavor, slight bitter, warm-natured, Return liver, stomach, has dissipate stasis of blood hemostasis, detumescence fixed The function of pain, clinic be mainly used for spitting of blood, haematemesis, bleeding from five sense organs or subcutaneous tissue, have blood in stool, uterine bleeding, traumatic hemorrhage, chest and abdomen are twinged with tumbling and swelling etc. Disease.
Radix Polygalae is milk wort Radix PolygalaePolygalatenuifoliaOr ovum leaf Radix Polygalae Willd.PolygalasibiricaL. dry root.Spring, the excavation of two season of autumn, remove fibrous root and silt, dry.This product bitter, property are pungent Temperature, the thoughts of returning home, kidney, lung channel have the function of that tranquilize the mind and promote the intelligence, restoring normal coordination between heart and kidney, eliminating the phlegm, detumescence etc., clinic are mainly used for breakdown of the normal physiological coordination between the heart and the kidney and draw The insomnia and dreamful sleep that rises, forgetful palpitation with fear, wandering, expectoration is not well, sore swollen toxin, the diseases such as mastosis.
Grass-leaved sweetflag is acorus gramineus araceae plantAcorustatarinowiiThe dry rhizome of Schott.Autumn, two season of winter Excavation removes fibrous root and silt, dries.This product bitter, property pungent-warm, the thoughts of returning home, stomach have have one's ideas straightened out slit phlegm, inducing resuscitation intelligence development, dampness elimination The effect of appetizing, clinic are mainly used for the diseases such as coma epilepsy, forgetful insomnia, Hiccough and deaf, gastral cavity ruffian is not hungry, apnea.
Poria cocos is On Polyporaceae Poria cocosPoriacocos(Schw.) dry sclerotia of Wolf.It is excavated more than 7~September, Silt is removed, is banked up " sweating ", cutting is block.This product is sweet in flavor, light, mild-natured, the thoughts of returning home, lung, spleen, kidney channel, tool clearing damp and promoting diuresis, invigorating the spleen The function of calming heart is mainly used for oedema oliguria, and phlegm retention anti-dazzle nervous, spleen eating less, loose stool diarrhea is confused and worried, the diseases such as insomnia of palpitating with fear.
Rhizoma Gastrodiae is the dry tuber of orchid Rhizoma Gastrodiae Gastrodiaelata Bl., and alias rhizoma gastrodiae, solely shakes at wind grass It is blue, from it is female, close from grass.《Compendium of Materia Medica》It carries:" rhizoma gastrodiae is acrid in flavour and warm in nature, nontoxic, long term usage benefiting energy, and long cloudy fertilizer is strong, makes light of one's life by commiting suicide and increases year.”《God Agriculture book on Chinese herbal medicine passes through》It is classified as top grade, it is believed that it has the effect of " main to kill terrible smart object, disease due to noxious agents produced by various parasites bad odor ".Clinic is mainly used for treating The diseases such as headache, insomnia.
Radix Notoginseng is longer than promoting blood circulation and removing blood stasis, simultaneous energy tonifying Qi and blood, for monarch drug in a prescription in side;Poria cocos dampness removing invigorating the spleen calming heart, Radix Polygalae are calmed the nerves beneficial Intelligence, grass-leaved sweetflag inducing resuscitation, Rhizoma Gastrodiae benefiting qi for tranquillization are helped for minister.Full side's five tastes drug complements each other, and plays tonifying Qi and blood, dampness removing altogether Invigorating the spleen, work(promoting blood circulation and removing blood stasis, refreshment and tranquilization, have benefit, bowl spares band to let out, therefore can reach the good result for the treatment of both manifestation and root cause of disease in attacking.
The second object of the present invention, which is achieved in that, to be included the following steps:
A, ingredients is weighed by prescription, Radix Notoginseng, Radix Polygalae and Rhizoma Gastrodiae pulverize and sieve, and it is segment that grass-leaved sweetflag is cataclasm, and Poria cocos is cataclasm to be Fritter, it is spare;
B, above-mentioned Radix Notoginseng, Radix Polygalae, Rhizoma Gastrodiae, grass-leaved sweetflag and Poria cocos medicinal material are placed in container, solvent is added, closed immersion obtains object Expect a;
C, by above-mentioned material a, that is, in the medicinal material and soak filling percolator after impregnating, solvent is added and carries out diacolation, collection is oozed It filters liquid, vacuum is dusted dry to get pharmaceutical composition of the present invention.
The third object of the present invention be achieved in that by pharmaceutical composition of the present invention with it is pharmaceutically acceptable Auxiliary material or auxiliary agent are made, including powder, tablet, sublingual tablet, buccal tablets, capsule, granule, spray, aerosol, patch Agent, cataplasm, paste, liniment, oral solution, dripping pill, honey pill agent.
The pharmaceutical preparation of the present invention, can be liquid preparation, can also be solid pharmaceutical preparation or semisolid preparation.Liquid preparation Can be solution (including true solution and colloidal solution), emulsion (including o/w types, w/o types and emulsion), suspension, injection (including liquid drugs injection, powder-injection and infusion), eye drops, nasal drop, lotion, oral solution and liniment etc.;Solid pharmaceutical preparation can be piece Agent (including ordinary tablet, enteric coatel tablets, lozenge, dispersible tablet, chewable tablets, effervescent tablet, oral disnitegration tablet, sustained release tablets, controlled release tablet), capsule Agent (including hard capsule, soft capsule, capsulae enterosolubilis, spansule, controlled release capsule), granule, powder, pellet, dripping pill, suppository, Film, patch, the agent of gas (powder) mist, spray etc.;Semisolid preparation can be ointment, gelling agent, paste etc..
In order to which tablet is made in pharmaceutical composition of the present invention, various figurations well known in the art can be widely used Agent, including diluent, binder, wetting agent, disintegrant, lubricant, glidant.Diluent can be starch, dextrin, sucrose, Glucose, lactose, mannitol, sorbierite, xylitol, microcrystalline cellulose, calcium sulfate, calcium monohydrogen phosphate, calcium carbonate etc.;Wetting agent can To be water, ethyl alcohol, isopropanol etc.;Adhesive can be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, Mucialga of arabic gummy, gelatine size, sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methyl cellulose, ethyl cellulose, propylene Acid resin, carbomer, polyvinylpyrrolidone, polyethylene glycol etc.;Disintegrant can be dried starch, microcrystalline cellulose, low substitution Hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, croscarmellose sodium, sodium carboxymethyl starch, sodium bicarbonate and Chinese holly Rafter acid, polyoxyethylene sorbitol aliphatic ester, dodecyl sodium sulfate etc.;Lubricant and glidant can be talcum powder, two Silica, stearate, tartaric acid, atoleine, polyethylene glycol etc..Tablet can also be further made to coating tablet, such as Sugar coated tablet, thin membrane coated tablet, enteric coated tablets or double-layer tablets and multilayer tablet.
In order to which capsule is made in pharmaceutical composition of the present invention, it can be mixed with diluent, glidant, it will Mixture is placed directly in hard capsule or soft capsule.It also can be first made with diluent, binder, disintegrant to particle or micro- Ball, then be placed in hard capsule or soft capsule.
In order to which liquid preparation or semisolid preparation is made in pharmaceutical composition of the present invention, water, ethyl alcohol, different can be used Propyl alcohol, propylene glycol, polyethylene glycol or their mixture as solvent, and be added appropriate solubilizer commonly used in the art, cosolvent, PH adjusting agent, osmotic pressure regulator, flavoring agent, thickener etc..
In addition, if desired, colorant, preservative, fragrance, corrigent or other additions can also be added into pharmaceutical preparation Agent.
To reach medication purpose, enhance therapeutic effect, drug of the invention or pharmaceutical composition, pharmaceutical preparation can be with any Well known medication administration.
The dosage of pharmaceutical composition of the present invention or its preparation, according to the property to be prevented or be treated disease And severity, the individual instances of patient or animal, administration route and dosage form etc. can have large-scale variation.In general, The daily Suitable dosage ranges of pharmaceutical composition of the present invention or its preparation are 0.001 ~ 10000mg/Kg weight, preferably For 0.01 ~ 1000mg/Kg weight, more preferably 0.1 ~ 500mg/Kg weight.Above-mentioned dosage with a dosage unit or can be divided into Several dosage unit administrations, this depends on the clinical experience of doctor and includes the dosage regimen with other treatment means.
Pharmaceutical composition of the present invention or its preparation can individually be taken, or be closed with other treatment drug or symptomatic drugs And it uses.When the compound of the present invention and other medicines, which exist, to act synergistically, its agent should be adjusted according to actual conditions Amount.
The fourth object of the present invention is achieved in that the pharmaceutical composition is preparing prevention and/or treatment cognition Application in dysfunction disease drug.
The cognition dysfunction disease includes Alzheimer's disease, vascular dementia and mild cognition impairment disease Deng.
The present invention is with Doneppezil Hydrochloride(Aricept)For control drug, using NIH mouse Alzheimer disease models, Improvement result and Mechanism Study of the pharmaceutical composition of the present invention to Alzheimer's disease cognitive function in mice are carried out, as a result table Bright, drug of the present invention, which has the cognitive function of Alzheimer's disease mouse, to be significantly improved and improvement result, and A Erci is can be used for The treatment of the silent disease in sea.This research also found that NO, NOS and iNOS content in medication therapy groups Mice brain tissues of the present invention are equal Be decreased obviously compared with model group, prompt drug of the present invention may be by the NOS in inhibition Alzheimer's disease Mice brain tissues and The activity of iNOS, and then the excess generation of NO is reduced, mitigate damages of the NO to nerve cell, to improve and improve small Mouse cognitive function plays the role of preventing and treating Alzheimer's disease.See experimental example 1.
The present invention, using SD rat aorta dementia models, has carried out drug of the present invention using Nimodipine as control drug To the improvement therapeutic effect of vascular dementia rats cognitive function and Mechanism Study, the results showed that, pharmaceutical composition pair of the present invention Vascular dementia rats cognitive function is significantly improved and improvement result, can be used for the treatment of blood vessel nature feeble-mindedness.This research is also It was found that AChE activity, MDA and the lipofuscin content of medicine group of the present invention are substantially reduced compared with model group, drug tool of the present invention is prompted There is the effect for reducing that vascular dementia rats brain tissue Ach is horizontal, and free radical is inhibited to generate, this may be drug tool of the present invention There is the inherent mechanism of action of prevention and treatment vascular dementia.See experimental example 2.
In conclusion drug of the present invention is formed by Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae five tastes drug scientific compatibility, Fang Zhong, Radix Notoginseng are monarch, and Poria cocos, Radix Polygalae peace, grass-leaved sweetflag, Rhizoma Gastrodiae are helped for minister, and full presciption medicine object complements each other, and plays tonifying Qi and blood, work altogether Blood stagnation resolvation, dampness removing invigorating the spleen, refreshment and tranquilization work(, there is benefit, bowl spares band to let out in attacking, Alzheimer disease, vascular dementia etc. recognized Know that dysfunction disease has the good result for the treatment of both manifestation and root cause of disease.Compared with existing product technology, drug of the present invention have prescription essence it is small, It is significant in efficacy, it is safe and non-toxic, the features such as treating both manifestation and root cause of disease, it is especially suitable for person in middle and old age and slow disease patient uses, there is high clinic Value, wide market.
Specific implementation mode
With reference to embodiment, the present invention is further illustrated, but is not limited in any way to the present invention, Based on present invention teach that made by it is any transform or replace, all belong to the scope of protection of the present invention.
The pharmaceutical composition for the treatment of cognition dysfunction of the present invention by 10 ~ 90 parts of the Radix Notoginseng of parts by weight, Poria cocos 10 ~ 2 ~ 40 parts of 90 parts, 5 ~ 60 parts of Radix Polygalae, 5 ~ 60 parts of grass-leaved sweetflag and Rhizoma Gastrodiae form.
The pharmaceutical composition of the described treatment cognition dysfunction by 15 ~ 70 parts of the Radix Notoginseng of parts by weight, 15 ~ 70 parts of Poria cocos, 2 ~ 40 parts of 10 ~ 50 parts of Radix Polygalae, 10 ~ 50 parts of grass-leaved sweetflag and Rhizoma Gastrodiae compositions.
The pharmaceutical composition of the treatment cognition dysfunction is by 50 parts of the Radix Notoginseng of parts by weight, 50 parts of Poria cocos, Radix Polygalae 30 20 parts of part, 30 parts of grass-leaved sweetflag and Rhizoma Gastrodiae compositions.
The preparation method of pharmaceutical composition of the present invention, includes the following steps:
A, ingredients is weighed by prescription, Radix Notoginseng, Radix Polygalae and Rhizoma Gastrodiae pulverize and sieve, and it is segment that grass-leaved sweetflag is cataclasm, and Poria cocos is cataclasm to be Fritter, it is spare;
B, above-mentioned Radix Notoginseng, Radix Polygalae, Rhizoma Gastrodiae, grass-leaved sweetflag and Poria cocos medicinal material are placed in container, solvent is added, closed immersion obtains object Expect a;
C, by above-mentioned material a, that is, in the medicinal material and soak filling percolator after impregnating, solvent is added and carries out diacolation, collection is oozed Filter liquid, vacuum dust it is dry to get.
Pulverize and sieve in step A is that crushed 10 mesh sieve;The length of segment is 0.5 ~ 5cm, the length of side of fritter is 0.5 ~ 5cm。
Solvent is the ethyl alcohol of concentration expressed in percentage by volume 50 ~ 100% in step B, and addition is 6 ~ 12 times of medicinal material total weight, leaching The bubble time is 48 ~ 96h.
Solvent is the ethyl alcohol of concentration expressed in percentage by volume 50 ~ 100% in step C, and addition is 20 ~ 40 times of medicinal material total weight, is oozed The time filter as 12 ~ 72h.
In step C vacuum dust dry temperature be 40 ~ 70 DEG C.
Pharmaceutical preparation of the present invention by pharmaceutical composition of the present invention and pharmaceutically acceptable auxiliary material or helps Agent is made, including powder, tablet, sublingual tablet, buccal tablets, capsule, granule, spray, aerosol, patch, cataplasm, Paste, liniment, oral solution, dripping pill, honey pill agent.
The preparation includes regular pharmaceutics, sustained release preparation or controlled release preparation.
The application of the compositions is that the pharmaceutical composition is preparing prevention and/or treatment cognition dysfunction Application in disease drug.
The application of the pharmaceutical composition is that the pharmaceutical composition is preparing prevention and/or treatment Alzheimer Application in disease drug.
The application of the pharmaceutical composition is that the pharmaceutical composition is preparing prevention and/or treatment vascular dementia Application in drug.
The application of the pharmaceutical composition is that the pharmaceutical composition is preparing prevention and/or treatment mild cognitive work( Application in energy disorder remedies.
With specific embodiment, the present invention will be further described below:
(Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 9 for the preparation of 1 1# pharmaceutical compositions of embodiment:6:3:3: 1)
Prescription:90 kg of Radix Notoginseng, 60 kg of Poria cocos, 30 kg of Radix Polygalae, 30 kg of grass-leaved sweetflag, 10 kg of Rhizoma Gastrodiae.
Preparation method:
(1)Ingredients is weighed by prescription, Radix Notoginseng, Radix Polygalae and Rhizoma Gastrodiae are crushed to most coarse powder(Cross 10 mesh sieve), grass-leaved sweetflag is cataclasm to be The segment of 0.5-5cm long, it is fritter that the length of side is 0.5-5cm that Poria cocos is cataclasm, spare;
(2)Radix Notoginseng, Radix Polygalae, Rhizoma Gastrodiae, grass-leaved sweetflag and the Poria cocos that upper step preprocessing is handled, are placed in container, and 1350 kg bodies are added The ethyl alcohol that product percentage concentration is 95%, closed immersion 48h;
(3)Medicinal material and soak after upper step is impregnated are packed into percolator, and it is 95% that 4400 kg concentration expressed in percentage by volumes, which are added, The continuous diacolation 12h of ethyl alcohol, collect diacolation liquid, dust in 40 DEG C of vacuum dry to get object 1# pharmaceutical compositions.
(Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 1 for the preparation of 2 2# pharmaceutical compositions of embodiment:9: 5:3:3)
Prescription:10 kg of Radix Notoginseng, 90 kg of Poria cocos, 50 kg of Radix Polygalae, 30 kg of grass-leaved sweetflag, 30 kg of Rhizoma Gastrodiae.
Preparation method:
(1)Ingredients is weighed by prescription, Radix Notoginseng, Radix Polygalae and Rhizoma Gastrodiae are crushed to most coarse powder(Cross 10 mesh sieve), grass-leaved sweetflag is cataclasm to be The segment of 0.5-5cm long, it is fritter that the length of side is 0.5-5cm that Poria cocos is cataclasm, spare;
(2)Radix Notoginseng, Radix Polygalae, Rhizoma Gastrodiae, grass-leaved sweetflag and the Poria cocos that upper step preprocessing is handled, are placed in container, and 1700 kg bodies are added The ethyl alcohol that product percentage concentration is 80%, closed immersion 72h;
(3)Medicinal material and soak after upper step is impregnated are packed into percolator, and it is 80% that 5000kg concentration expressed in percentage by volumes, which are added, The continuous diacolation of ethyl alcohol for 24 hours, collects diacolation liquid, dusts in 50 DEG C of vacuum dry to get object 2# pharmaceutical compositions.
(Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 3 for the preparation of 3 3# pharmaceutical compositions of embodiment:1: 6:7:5)
Prescription:30 kg of Radix Notoginseng, 10 kg of Poria cocos, 60 kg of Radix Polygalae, 70 kg of grass-leaved sweetflag, 50 kg of Rhizoma Gastrodiae.
Preparation method:
(1)Ingredients is weighed by prescription, Radix Notoginseng, Radix Polygalae and Rhizoma Gastrodiae are crushed to most coarse powder(Cross 10 mesh sieve), grass-leaved sweetflag is cataclasm to be The segment of 0.5-5cm long, it is fritter that the length of side is 0.5-5cm that Poria cocos is cataclasm, spare;
(2)Radix Notoginseng, Radix Polygalae, Rhizoma Gastrodiae, grass-leaved sweetflag and the Poria cocos that upper step preprocessing is handled, are placed in container, and 2200 kg bodies are added The ethyl alcohol that product percentage concentration is 75%, closed immersion 84h;
(3)Medicinal material and soak after upper step is impregnated are packed into percolator, and it is 75% that 6600kg concentration expressed in percentage by volumes, which are added, The continuous diacolation 48h of ethyl alcohol collects diacolation liquid, dusts in 60 DEG C of vacuum dry to get object 3# pharmaceutical compositions.
(Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 5 for the preparation of 4 4# pharmaceutical compositions of embodiment:5: 3:3:2)
Prescription:50 kg of Radix Notoginseng, 50 kg of Poria cocos, 30 kg of Radix Polygalae, 30 kg of grass-leaved sweetflag, 20 kg of Rhizoma Gastrodiae.
Preparation method:
(1)Ingredients is weighed by prescription, Radix Notoginseng, Radix Polygalae and Rhizoma Gastrodiae are crushed to most coarse powder(Cross 10 mesh sieve), grass-leaved sweetflag is cataclasm to be The segment of 0.5-5cm long, it is fritter that the length of side is 0.5-5cm that Poria cocos is cataclasm, spare;
(2)Radix Notoginseng, Radix Polygalae, Rhizoma Gastrodiae, grass-leaved sweetflag and the Poria cocos that upper step preprocessing is handled, are placed in container, and 2160 kg bodies are added The ethyl alcohol that product percentage concentration is 50%, closed immersion 96h;
(3)Medicinal material and soak after upper step is impregnated are packed into percolator, and it is 50% that 7200kg concentration expressed in percentage by volumes, which are added, The continuous diacolation 72h. of ethyl alcohol collects diacolation liquid, dusts in 70 DEG C of vacuum dry to get object 4# pharmaceutical compositions.
5 powder of embodiment
1# pharmaceutical compositions prepared by Example 1, are distributed into bag, become powder.
6 tablet of embodiment
Medicament composing prescription(Weight percent):
2# pharmaceutical compositions 10% prepared by embodiment 2
Starch 82%
Microcrystalline cellulose 8%
Total 100%
Preparation method:It is matched according to said medicine prescription, 2# pharmaceutical compositions prepared by embodiment 2 and starch, microcrystalline cellulose Element after mixing, in tabletting on tablet press machine to get.
7 capsule of embodiment
Medicament composing prescription(Weight percent):
3# pharmaceutical compositions 25% prepared by embodiment 3
Starch 65%
Magnesium stearate 10%
Total 100%
Preparation method:It is matched according to said medicine prescription, 3# pharmaceutical compositions prepared by embodiment 3 and starch, magnesium stearate After mixing, be filled in hard gelatin capsule to get.
8 granule of embodiment
Medicament composing prescription(Weight percent):
4# pharmaceutical compositions 30% prepared by embodiment 4
Dextrin 50%
Sucrose 20%
Total 100%
Preparation method:It is matched according to said medicine prescription, 4# pharmaceutical compositions and dextrin prepared by embodiment 4, sucrose is mixed Uniformly after, be granulated, enfeoffment be loaded on aluminum foil bag in get.
9 oral solution of embodiment
Medicament composing prescription(Weight percent):
1# pharmaceutical compositions 10% prepared by embodiment 1
Honey 5%
Distilled water 85%
Total 100%
Preparation method:It is matched according to said medicine prescription, 1# pharmaceutical compositions and honey prepared by embodiment 1 is placed in distilled water In, stir evenly, be packaged in vial, sterilizing to get.
Improvement result and Mechanism Study of the experimental example 1 to Alzheimer disease model cognitive function in mice
1. experimental drug and material
1# pharmaceutical compositions:Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 9:6:3:3:1, implement by the present invention It is prepared by example 1.
2# pharmaceutical compositions:Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 1:9:5:3:3, by the present invention It is prepared by embodiment 2.
3# pharmaceutical compositions:Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 3:1:6:7:5, by the present invention It is prepared by embodiment 3.
4# pharmaceutical compositions:Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 5:5:3:3:2, by the present invention It is prepared by embodiment 4.
Control drug:Doneppezil Hydrochloride, trade name Aricept defend material (China) pharmaceutcal corporation, Ltd product.
NO, NOS and iNOS kit:Bioengineering Research Institute's offer is built up in Nanjing.
Aβ1-42:Anaspec Products.
2. experimental animal
Healthy adult male NIH mouse, 9 week old, weight 18~20.
3. testing key instrument and equipment
III circulating water type vacuum pumps of SHZ-DC, ST-3ND mouse stereotaxic apparatus, DMS-2 type Morris water maze instrument data Automatic collection and processing system.
4. experimental method
4.1 groupings and administration
Healthy adult male NIH mouse 70 are randomly divided into Normal group, model group, 1# pharmaceutical compositions group, 2# medicine groups Conjunction object group, 3# pharmaceutical compositions group, 4# pharmaceutical compositions group and control drug Doneppezil Hydrochloride group, every group 10.Mouse is used Yellow Jackets are anaesthetized (50 mg/kg, ip).Mouse is fixed with stereotaxic apparatus cranium head position of making even, cuts off scalp, cruelly Reveal bregma, positioned by mouse brain stereotaxic atlas, selects 2 mm after bregma, 1.5 mm of median line side, skull surface It is bilateral hippocampus CA1 injection points at lower 1. 9 mm, A β is slowly injected into micro syringe1-42(2 g/L of concentration, often 2 μ L of side, sample introduction speed are 0.8 μ L/min).Injection finishes, and sews up a wound, continuous 3 d intramuscular injection benzyl penicillin 8 × 10 5 U are to prevent infection.The same surgical procedure of Normal group mouse row, but A β are not injected1-42.After modeling success, normal group and Model group gives isometric distilled water gavage, daily 1 time;Remaining each group intragastric administration on mice gives reagent, one time a day, continuous 3 weeks Afterwards, water maze test is carried out.
4.2 water maze test
Morris water maze pool diameter 120cm, pond depth 50cm.Pond is divided into four with four equidistant points when experiment A quadrant area is located in fourth quadrant among pool wall and the center of circle, places organic glass platform.Add water into pond, the depth of water is about 20cm, the water surface are higher by platform surface 0.5cm, and 25+2 DEG C of water temperature injects milk powder, and mixing makes water at opaque milky, reaches Animal vision can not distinguish the purpose whether there is or not platform in pond, and enable a computer to successfully track the activity of mouse.Experiment is in sound insulation Room in carry out, the various experimental conditions such as pond position, light source position and intensity remain unchanged in the entire experiment process, with Come locating platform position for mouse.
Test program:It carries out 1 time daily, continuous training 5 days.Remove platform 5th day afternoon, an optional place of entry will Mouse is put into towards pool wall in pond, and camera system, which automatically records, passes in and out the number of Yuanping City's taiwan area and in original platform in mouse 3min The index of place fourth quadrant swimming time and distance as evaluation cognitive function in mice.
4.3 NO, NOS and iNOS are measured
For mouse through yellow Jackets intraperitoneal injection of anesthesia (50 mg/kg, ip), sacrificed by decapitation will rapidly in taking brain on ice chest Brain tissue is placed in ice-cold physiological saline and rinses, and filter paper blots, and weighs, and 10% brain homogenates, 4 DEG C, 3000 r/min are made 15 min are centrifuged, supernatant is taken, according to kit specification, measure NO contents and NOS, iNOS activity.
5. experimental result
Influence of 5.1 drugs to Alzheimer's disease model mice cognitive function
Influence (x ± s, n=10) of 1 drug of table to Alzheimer disease model cognitive function in mice
By upper table 1 it is found that compared with normal group, Alzheimer's disease model group mouse passes through original platform in Morris water mazes Position number, fourth quadrant swimming time and distance substantially reduce.After each medicine group treatment, mouse is in Morris water mazes Original platform position number, fourth quadrant swimming time and distance is passed through significantly to increase compared with model group, show each group drug to Ah The cognitive function of Er Cihaimo disease mouse is significantly improved and improvement result, wherein especially the brightest with the effect of 4# pharmaceutical compositions It is aobvious to protrude.Therefore, drug of the present invention can be used for the prevention and treatment of Alzheimer's disease.
Influence of 5.2 drugs to NO, NOS and iNOS in Alzheimer's disease Mice brain tissues
Influence of 2 drug of table to NO, NOS and iNOS in Alzheimer's disease Mice brain tissues
NO is the gaseous signal molecule between a kind of central nervous system cell, with the developing of nervous system, ripe, learning and memory Etc. closely related, Central nervous system not only has potential protective effect, but also has neurotoxic effect.Under normal condition, NO has the characteristic of endothelium source relaxing factor in body, can by vasodilator, increase cerebral blood flow (CBF), antiplatelet and white thin The aggregation of born of the same parents transmits with adherency, enhancing cynapse and the mechanism such as receptor is inhibited to play the role of neuroprotection;But internal NO is excessive When, NO can be by mediating the toxicity of excitatory amino acid, induced radical to generate, causing calcium overload, damage mitochondria and induction The mechanism such as Apoptosis to brain tissue generate neurotoxic effect, so as to cause or aggravate Alzheimer's disease.NOS is NO lifes The important rate-limiting enzyme of object synthesis is to determine that NO plays the key factor of damage or protection double action.It has determined at present NOS has Neuronal Nitric Oxide Synthase (nNOS), endothelial nitric oxide synthase (eNOS), inducible nitric oxide 3 kinds of hypotypes of synthase (iNOS).Wherein, iNOS acts on the formation and evolution of Alzheimer's disease maximum, and the duration is long, It can be catalyzed and generate a large amount of NO, be the major reason that Alzheimer's disease aggravates.Remove the NO in brain tissue or inhibition The activity of NOS can effectively mitigate Alzheimer symptom.This result of study finds, NO contents in model group Mice brain tissues Obviously increase with NOS, iNOS activity, prompting the raising of NO contents may originate from, NOS is active to be increased, and increased NO may cause or aggravate Alzheimer's disease by the neurotoxic effect of its mediation.
This result of study is found(It is shown in Table 2), compared with normal group, in Alzheimer's disease model group Mice brain tissues NO, NOS and iNOS content are significantly raised, and each treatment group NO, NOS and iNOS content is decreased obviously compared with model group.This is carried Show that each group drug may be by inhibiting the activity of NOS and iNOS in Alzheimer's disease Mice brain tissues, and then reduces NO Excess generation, mitigate damages of the NO to nerve cell, to play the role of raising and improve cognitive function in mice.This can Can be the inherent mechanism of action of the above medical treatment Alzheimer disease.
6. conclusion
The present invention is with Doneppezil Hydrochloride(Aricept)It is carried out using NIH mouse Alzheimer disease models for control drug Improvement result and Mechanism Study of the pharmaceutical composition of the present invention to Alzheimer's disease cognitive function in mice, the results showed that, this Invention drug, which has the cognitive function of Alzheimer's disease mouse, to be significantly improved and improvement result, and Alzheimer's disease is can be used for Treatment.This research also found that NO, NOS and iNOS content in medication therapy groups Mice brain tissues of the present invention are compared with model Group is decreased obviously, and drug of the present invention is prompted to may be by inhibiting the NOS and iNOS in Alzheimer's disease Mice brain tissues Activity, and then reduce the excess generation of NO, mitigate damages of the NO to nerve cell, to improve and improve mouse cognition Function plays the role of preventing and treating Alzheimer's disease.
Experimental example 2 is to the improvement therapeutic effect of vascular dementia rats cognitive function and Mechanism Study
1. experimental drug and material
1# pharmaceutical compositions:Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 9:6:3:3:1, implement by the present invention It is prepared by example 1.
2# pharmaceutical compositions:Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 1:9:5:3:3, by the present invention It is prepared by embodiment 2.
3# pharmaceutical compositions:Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 3:1:6:7:5, by the present invention It is prepared by embodiment 3.
4# pharmaceutical compositions:Radix Notoginseng, Poria cocos, Radix Polygalae, grass-leaved sweetflag, Rhizoma Gastrodiae prescription proportioning are 5:5:3:3:2, by the present invention It is prepared by embodiment 4.
Control drug Nimodipine:Bayer HealthCare Co provides.
Malonaldehyde (malondiadehyde, MDA), acetylcholinesterase (acetylcholineesterase, AChE), lipofuscin kit:Bioengineering Research Institute's offer is built up in Nanjing.
2. experimental animal
SD rats, 180 ~ 220 g of weight, half male and half female.
3. testing key instrument and equipment
DTT-2 type rat diving tower instrument, the program-controlled rat of DBA-2 types keep away camera bellows, institute of Materia Medica,Chinese Academy of Medical Sciences; RF- 5000 type sepectrophotofluorometers, Japanese Shimadzu Corporation;The full-automatic microplate reader of EL340 types, U.S. Bio- TekInstruments companies.
4. experimental method
4.1 groupings and administration
Healthy SD rat 70 is randomly divided into Normal group, model group, 1# pharmaceutical compositions group, 2# pharmaceutical compositions group, 3# Pharmaceutical composition group, 4# pharmaceutical compositions group and control drug Nimodipine group, every group 10.
Vascular dementia rats model is prepared with improvement tetra- blood vessel blocking methods of Pulsinelli, specific method is:Rat In 12 h of pre-operative anxiety, water can't help, after yellow Jackets intraperitoneal anesthesia, rat prostrate is fixed, row back side neck center Notch, successively blunt separation, exposes the 1st transverse process of cervical vertebra wing aperture of bilateral.It is dynamic with the vertebra in coagulation needle calcination double side wings aperture Arteries and veins, causes permanent occlusion, then rat is lain on the back fixation, row veutro neck median incision, blunt separation bilateral common carotid arteries, It is spare with " 4 " number silk thread threading.After for 24 hours, bilateral common carotid arteries 5min is closed with arteriole folder folder, presss from both sides and closes again after 1 h of interval 5min is pressed from both sides close 3 times altogether.Before local wound suture, being handled with gentamicin localized pulverization prevents from infecting, and postoperative 3 d gives It is anti-infective to give 200,000 U of penicillin/kg intramuscular injection.Sham-operation group step is same as above, and does not do ischemic preconditioning.Postoperative 10 d is opened Begin, each medicine group continuous gavage administration daily 1 time, after 15d, carries out step down test and keeps away dark experiment.Normal group and model Group gives isometric distilled water gavage, daily 1 time.
4.2 step down test
There are two reaction chambers for rat DTT-2 type diving towers instrument, are divided between two, and bottom is spread can lead to the copper of the continuous electro photoluminescence of 36V Grid, every left rear corner set a diameter and height be 10 cm valve rubber be used as diving tower, this for rat avoid shock by electricity safety Area.Two rats of every batch of are respectively put into two grid of diving tower instrument simultaneously when training.Environment 3min is first adapted to, then It is powered, rat is shocked by electricity on copper grid, and most normal reactions are jumped on valve rubber, escapes electric shock.With rat when jumping off It is to get an electric shock that biped contacts copper grid simultaneously, is considered as wrong reaction, so trains 5min.It retests afterwards for 24 hours, it is first when test Rat is placed on valve rubber, starts simultaneously at and clocks, record rat jumps off the time for the first time, this (is to get an electric shock incubation period Error latence), and the number (being errors number) jumped in 5 min on copper grid is recorded, as observation index.
4.3 keep away dark experiment
The program-controlled camera bellows of keeping away of rat DBA-2 types is two reaction chambers, is divided into two Room of light and shade, structure keeps away camera bellows similar to mouse is program-controlled. 2 rats of every batch of are respectively put into bright room when training and adapt to 3 min of environment, are then electrified to.Rat pierces because of thermophilic dark habit Darkroom then gets shocked, and animal can voluntarily escape from darkroom and return to bright room at this time, to be remembered, so 5 min of training. It is retested after 24 h, when test is first powered, and rat is then put into bright room back to hole, starts simultaneously at and clocks, and records Rat enters in the time (being incubation period) shocked by electricity in darkroom and 5 min from bright room to first time is put into darkroom Errors number, as observation index.
The measurement of 4.4 brain tissue AchE, MDA and lipofuscin
After the completion of above-mentioned Animal Behavior Science experiment.Sacrificed by decapitation animal claims rapidly in taking its full brain (decerebellation) on ice chest Weight is made 10 % brain homogenates with sterile saline homogenate, presses malonaldehyde (MDA), acetylcholinesterase respectively (AChE), lipofuscin kit illustrates to carry out vitality test.
5. experimental result
Influence of the drug to vascular dementia rats cognitive function in 5.1 step down tests
In 3 step down test of table, influence (x ± s, n=10) of the drug to vascular dementia rats cognitive function
Group Dosage(mg/kg) Errors number(It is secondary) Incubation period(s)
Normal group Isometric distilled water 1.02±0.63 239.53±60.33
Model group Isometric distilled water 3.85±1.89 58.64±16.27
1# pharmaceutical compositions 50mg 1.58±0.83 183.62±47.02
2# pharmaceutical compositions 50mg 1.36±0.71 196.52±49.17
3# pharmaceutical compositions 50mg 1.93±0.97 176.83±43.16
4# pharmaceutical compositions 50mg 1.07±0.65 208.47±51.69
Nimodipine 50mg 1.96±1.01 177.09±45.14
By table 3 as it can be seen that in step down test, model group vascular dementia rats errors number, which is more normally organized, obviously to be increased, and each Treatment group's errors number is decreased obviously compared with model group;Compared with normal group, the incubation period of model group rats is obviously shortened, and respectively controls Treatment group incubation period is obviously prolonged compared with model group.It is above-mentioned the experimental results showed that, cognition of the drug of the present invention to vascular dementia rats Function is significantly improved and improvement result, wherein especially the most obviously being protruded with the effect of 4# pharmaceutical compositions.Therefore, of the invention Drug can be used for the prevention and treatment of vascular dementia.
5.2 keep away influence of the drug to vascular dementia rats cognitive function in dark experiment
Table 4 is kept away in dark experiment, influence (x ± s, n=10) of the drug to vascular dementia rats cognitive function
Group Dosage(mg/kg) Errors number(It is secondary) Incubation period(s)
Normal group Isometric distilled water 1.51±0.72 195.63±51.37
Model group Isometric distilled water 5.96±1.98 38.90±10.52
1# pharmaceutical compositions 50mg 2.07±0.93 152.38±39.06
2# pharmaceutical compositions 50mg 1.85±0.81 163.48±41.29
3# pharmaceutical compositions 50mg 2.52±1.09 136.56±33.87
4# pharmaceutical compositions 50mg 1.57±0.76 182.36±46.83
Nimodipine 50mg 2.26±0.98 149.62±38.17
By table 4 as it can be seen that in keeping away dark experiment, model group vascular dementia rats errors number, which is more normally organized, obviously to be increased, and each Treatment group's errors number is decreased obviously compared with model group;Compared with normal group, the incubation period of model group rats is obviously shortened, and respectively controls Treatment group incubation period is obviously prolonged compared with model group.It is above-mentioned the experimental results showed that, cognition of the drug of the present invention to vascular dementia rats Function is significantly improved and improvement result, wherein especially the most obviously being protruded with the effect of pharmaceutical composition 4.Therefore, of the invention Drug can be used for the prevention and treatment of vascular dementia.
Influence of 5.3 drugs to vascular dementia rats brain tissue AChE activity, MDA and lipofuscin content
5 drug of table to vascular dementia rats brain tissue AChE activity, MDA and lipofuscin content influence (x ± s, n= 10)
Group Dosage(mg/kg) AchE(U/mg protein) MDA(U/mg protein) Lipofuscin (μ g/g)
Normal group Isometric distilled water 0.81±0.16 19.26±3.72 0.31±0.09
Model group Isometric distilled water 1.43±0.27 57.42±13.48 1.52±0.29
1# pharmaceutical compositions 50mg 1.08±0.22 42.09±9.03 0.43±0.13
2# pharmaceutical compositions 50mg 0.95±0.19 38.59±8.26 0.38±0.11
3# pharmaceutical compositions 50mg 1.15±0.28 43.75±9.89 0.52±0.15
4# pharmaceutical compositions 50mg 0.89±0.18 32.79±6.74 0.29±0.08
Nimodipine 50mg 0.99±0.21 41.95±8.94 0.62±0.18
Vascular dementia is that cognitive function hinders caused by ischemic or hemorrhagic cerebrovaseular disease and global cerebral ischemia anoxic Hinder.Modern research shows that the cholinergic system of brain tissue takes part in the generation, development and evolution of vascular dementia.Acetylcholine (Ach) it is a kind of neurotransmitter related with learning and memory, the cholinergic neuron forfeiture in dementia patients brain, Ach levels are shown It writes and reduces.MDA is main metabolites of the free radical to biological cell membrane damage, is the decomposition product of lipid peroxide, It can make biomembrane denaturation, necrosis, so that DNA is mutated, interlinkage, while make the reduction of SOD activity, cause free radical chain anti- The vicious circle answered.Existing research thinks that free radical can lead to the destruction of unsaturated fatty acid and peroxide on cell and cell membrane Change and the generation of MDA, to generate significantly damages effect to the cognitive function of human body.
By table 5 as it can be seen that compared with normal group, model group vascular dementia rats brain tissue AchE, MDA and lipofuscin Content is significantly raised, and each medicine group AchE, MDA and lipofuscin are decreased obviously compared with model group.This prompts drug of the present invention to have drop Low vascular dementia rats brain tissue Ach is horizontal, the effect for inhibiting free radical to generate, this, which may be drug of the present invention, has in advance Anti- and treatment vascular dementia the inherent mechanism of action.
6. conclusion
The present invention, using SD rat aorta dementia models, has carried out drug of the present invention to blood using Nimodipine as control drug The improvement therapeutic effect of pipe dementia rats cognitive function and Mechanism Study, the results showed that, pharmaceutical composition of the present invention is to blood vessel Dementia rats cognitive function is significantly improved and improves, and can be used for the treatment of blood vessel nature feeble-mindedness.This research it has also been found that, this hair AChE activity, MDA and the lipofuscin content of bright medicine group are substantially reduced compared with model group, and prompting drug of the present invention to have reduces blood Pipe dementia rats brain tissue Ach is horizontal, the effect for inhibiting free radical to generate, this may be drug of the present invention have prevent and Treat the inherent mechanism of action of vascular dementia.
The above is only presently preferred embodiments of the present invention, is not intended to limit the present invention in any form, though So the present invention has been disclosed as a preferred embodiment, and however, it is not intended to limit the invention, the technology people of any familiar present invention Member without departing from the scope of the present invention, when the technology contents using above-mentioned prompt make it is a little variation or be modified to The equivalent embodiment of equivalent variations, it is right according to the technical essence of the invention as long as being the content without departing from technical solution of the present invention Any simple modification, equivalent change and modification made by above example, in the range of still falling within the present invention program.

Claims (14)

1. a kind of pharmaceutical composition, it is characterised in that the pharmaceutical composition by 10 ~ 90 parts of the Radix Notoginseng of parts by weight, Poria cocos 10 ~ 2 ~ 40 parts of 90 parts, 5 ~ 60 parts of Radix Polygalae, 5 ~ 60 parts of grass-leaved sweetflag and Rhizoma Gastrodiae form.
2. pharmaceutical composition according to claim 1, it is characterised in that the pharmaceutical composition by parts by weight Radix Notoginseng 2 ~ 40 parts of 15 ~ 70 parts, 15 ~ 70 parts of Poria cocos, 10 ~ 50 parts of Radix Polygalae, 10 ~ 50 parts of grass-leaved sweetflag and Rhizoma Gastrodiae form.
3. according to any pharmaceutical composition of claim 1 ~ 2, it is characterised in that the pharmaceutical composition is by parts by weight 50 parts of Radix Notoginseng, 50 parts of Poria cocos, 30 parts of Radix Polygalae, 30 parts of grass-leaved sweetflag and 20 parts of Rhizoma Gastrodiae composition.
4. a kind of preparation method of any pharmaceutical composition of claim 1 ~ 3, it is characterised in that include the following steps:
A, ingredients is weighed by prescription, Radix Notoginseng, Radix Polygalae and Rhizoma Gastrodiae pulverize and sieve, and it is segment that grass-leaved sweetflag is cataclasm, and Poria cocos is cataclasm to be Fritter, it is spare;
B, above-mentioned Radix Notoginseng, Radix Polygalae, Rhizoma Gastrodiae, grass-leaved sweetflag and Poria cocos medicinal material are placed in container, solvent is added, closed immersion obtains object Expect a;
C, by above-mentioned material a, that is, in the medicinal material and soak filling percolator after impregnating, solvent is added and carries out diacolation, collection is oozed Filter liquid, vacuum dust it is dry to get.
5. preparation method according to claim 4, it is characterised in that it is that crushed 10 mesh sieve to pulverize and sieve in step A, small The length of section is 0.5 ~ 5cm, and the length of side of fritter is 0.5 ~ 5cm.
6. preparation method according to claim 4, it is characterised in that solvent is concentration expressed in percentage by volume 50 ~ 100% in step B Ethyl alcohol, addition is 6 ~ 12 times of prescription medicinal material weight, and soaking time is 48 ~ 96h.
7. preparation method according to claim 4, it is characterised in that solvent is concentration expressed in percentage by volume 50 ~ 100% in step C Ethyl alcohol, addition is 20 ~ 40 times of prescription medicinal material weight, and the diacolation time is 12 ~ 72h.
8. preparation method according to claim 4, it is characterised in that in step C vacuum dust dry temperature be 40 ~ 70 ℃。
9. a kind of pharmaceutical preparation, it is characterised in that by any pharmaceutical composition of claim 1 ~ 3 with it is pharmaceutically acceptable Auxiliary material or auxiliary agent be made, including powder, tablet, sublingual tablet, buccal tablets, capsule, granule, spray, aerosol, patch Agent, cataplasm, paste, liniment, oral solution, dripping pill, honey pill agent.
10. pharmaceutical preparation according to claim 9, it is characterised in that the pharmaceutical preparation includes regular pharmaceutics, sustained release Preparation or controlled release preparation.
11. a kind of application of any pharmaceutical composition of claim 1 ~ 3, it is characterised in that the pharmaceutical composition exists Prepare the application for preventing and/or treating in cognition dysfunction disease drug.
12. a kind of application of any pharmaceutical composition of claim 1 ~ 3, it is characterised in that the pharmaceutical composition exists Prepare the application for preventing and/or treating in Alzheimer disease drug.
13. a kind of application of any pharmaceutical composition of claim 1 ~ 3, it is characterised in that the pharmaceutical composition exists Prepare the application for preventing and/or treating in vascular dementia drug.
14. a kind of application of any pharmaceutical composition of claim 1 ~ 3, it is characterised in that the pharmaceutical composition exists Prepare the application for preventing and/or treating in mild cognition impairment drug.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110742972A (en) * 2019-11-14 2020-02-04 美国琛蓝营养制品股份有限公司 Traditional Chinese medicine composition with cognitive improvement effect and preparation method thereof and traditional Chinese medicine preparation
CN111569008A (en) * 2020-05-09 2020-08-25 昆明医科大学 A pharmaceutical composition for treating neurodegenerative diseases
CN116898929A (en) * 2023-07-21 2023-10-20 大彭世纪科技有限公司 Nerve-soothing brain-nourishing health-care soup

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