CN103566087B - Pharmaceutical composition for treating cognitive disorder and application thereof in preparation of medicine for treating Alzheimer disease - Google Patents
Pharmaceutical composition for treating cognitive disorder and application thereof in preparation of medicine for treating Alzheimer disease Download PDFInfo
- Publication number
- CN103566087B CN103566087B CN201310487271.XA CN201310487271A CN103566087B CN 103566087 B CN103566087 B CN 103566087B CN 201310487271 A CN201310487271 A CN 201310487271A CN 103566087 B CN103566087 B CN 103566087B
- Authority
- CN
- China
- Prior art keywords
- radix
- pharmaceutical composition
- extract
- group
- parts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the technical field of traditional Chinese medicine and specifically provides a pharmaceutical composition for treating cognitive disorder. The pharmaceutical composition is composed of astragalus root, scutellaria baicalensis, rhizoma alismatis, salviae miltiorrhizae and ginseng. The invention also discloses a novel usage of the pharmaceutical composition in preparation of medicine for perfecting Alzheimer disease. The pharmaceutical composition provided by the invention can inhibit the expression of APP, A beta-40 and A beta-42 in a brain tissue, greatly improve the learning and memory ability of a quasi dementia mouse caused by scopolamine and reduce the ACHE activity of the brain tissue, so that the pharmaceutical composition provided by the invention has a good anti-dementia effect. In senile dementia treatment, the pharmaceutical composition provided by the invention can greatly improve the sugar metabolism of a dementia rat model and can also increase the contents of noradrenaline, dopamine and serotonin in pallium of a rapid brain aging mouse.
Description
Technical field
The present invention relates to a kind of dull-witted pharmaceutical composition of preventing and treating, more particularly, to a kind of medicine for treating cognitive dysfunction
Compositions and its production and use, belong to technical field of Chinese medicines.
Background technology
Cognitive dysfunction refers to various degrees of Cognitive function damage caused by a variety of causes, be clinically one kind it is many
Morbidity and commonly encountered diseases.The pathogenic factor and mechanism of primary disease is still not very clear at present, and patient is usually from mild cognitive function
Infringement develops into dementia.As China progresses into aging society, the prevalence of cognitive dysfunction increases year by year.Recognize
Know that dysfunction becomes the important diseases for affecting middle-aged and elderly people Health and Living quality, the performance of cognitive dysfunction is not only wrapped
Dysmnesia, aphasia and visual space obstacle etc. are included, can also be with the affective behavior obstacle such as anxiety, depression, intense, impulsion.
Alzheimer, is also called alzheimer disease, belongs to a class disease of cognitive dysfunction, and its sickness rate is current
In trend is steeply risen, its mortality rate is only second to heart disease, tumor and apoplexy and occupies the 4th.The pathology of alzheimer disease becomes
Change, the obvious atrophy of cerebral cortex is morphologically mainly shown as, based on frontal lobe, temporal lobe, top.Convolutional atrophy narrows, brain ditch
Broadening, the ventricles of the brain expand；Main changes in histopathology is occurred in that outside brain cell by 42 ammonia of amyloid-beta
The amyloid plaques (senile plaque) that hypotype (the i.e. A β 42) aggregation of base acid peptide is formed (SP), and are occurred in that by thin in neuron
The neurofibrillary tangleses that the Tau albumen of born of the same parents' micro-pipe and Hyperphosphorylationof is constituted（NFT）.Because the generation of amyloid-beta increases
Or reduction is removed, the amyloid-beta of aggregation starts a series of pathology mistakes in neurodegeneration with dull-witted morbidity
Journey, i.e. amyloid hypothesis.The aggregation of A β 42 result in the formation of amyloid plaques, and start a series of and neuron and dash forward
Touch function exception, inflammatory reaction, the Hyperphosphorylationof of Tau albumen, neurofibrillary tangleses formation, neuronal death, neurotransmitter
Abnormal related change, ultimately results in the generation of dementia.Alzheimer disease clinic is with confusion, memory defects, personality and language
Speech obstacle is main performance.
Modern medicine has been carried out years of researches to the cause of disease and pathogenesis of alzheimer disease, but because its cause of disease is answered
It is miscellaneous, so far at present the understanding of the cause of disease to alzheimer disease and pathogenesis is focused primarily upon not yet is understood to its concrete link
Intracerebral chronic inflammatory disease and Cholinergic progressive caused by h and E factor declines, and main is more representative
Theory have:Lectin from hemolymph theory of radical damage theory, cholinergic theory, calcium overload theory and the traditional Chinese medical science etc..In treatment often
Often bring back to life medicine from cholinesterase inhibitor, glutamate receptor antagonists, cerebral vasodilator, brain metabolism and Chinese medicine enters
Row Comprehensive Treatment.
The alzheimer disease course of disease is longer, and treatment is slow, needs long-term prescription, and Chinese medicine has in terms for the treatment of senile dementia
Have the curative effect advantage of uniqueness, for senile dementia research more extensively with deeply.In Chinese patent 201010147176.1
A kind of Chinese medicine compound for treating senile dementia is disclosed, the compound recipe is by Radix Astragali 1-3 parts, Radix Polygoni Multiflori 1-3 parts, Herba Epimedii 1-3 parts, benefit
Intelligence core 1-2 part, Radix Salviae Miltiorrhizae 1-2 parts, Radix Polygalae 0.5-2 part, 0.5-2 parts of bending, Caulis Akebiae 0.5-2 parts, Cortex Moutan 0.5-2 parts, Rhizoma Chuanxiong 0.3-1
Part, Rhizoma Acori Graminei 1-3.5 parts, Rhizoma Alismatis 0.5-2 parts, Radix Angelicae Pubescentiss 0.5-2 parts, Radix Glycyrrhizae 0.5-2 parts, Herba Menthae 0.25-1 parts, Herba Schizonepetae 0.25-1
Part, Radix Gentianae Macrophyllae 0.25-1 parts, Radix Ginseng 0.25-1 parts composition.One kind is disclosed in Chinese patent 200910175365.7 and treats senile
Dull-witted Chinese medicine preparation.The Chinese medicine preparation is by Toxocarpus wightianus Hook. Et Arn 30-60 parts, little Jin tassel 25-50 parts, Microdesmis casearifolia plahch. 20-40 parts, Radix Rehmanniae Preparata 15-
30 parts, Rhizoma Dioscoreae 15-30 parts, Cortex Phellodendri 6-12 parts, Rhizoma Acori Graminei 15-30 parts, Radix Curcumae 12-24 parts, Rhizoma Gastrodiae 10-20 parts, Pheretima 12-24 parts,
Rhizoma Cyperi 10-20 parts, Radix Polygalae 10-20 part, Radix Ginseng 12-24 parts and Caulis Spatholobi 15-30 parts.It is public in Chinese patent 200610011484.5
A kind of Chinese medicine preparation for treating senile dementia of cloth, the Chinese medicine preparation is by 3～12 parts of the Radix Astragali, 1.5～6 parts of Radix Rehmanniae, Radix Curcumae 0.5
～2 parts, 1.5～6 parts of Poria, 1.5～6 parts of Rhizoma Acori Graminei, 0.5～2 part of Radix Ginseng, 1.5～6 parts of Fructus Lycii, Fructus Alpiniae Oxyphyllae 1.5～6 part, day
1.5～6 parts of fiber crops, 1.5～6 parts of the Rhizoma Anemarrhenae, 1.5～6 parts of Radix Cyathulae, 1.5～6 parts of Rhizoma Chuanxiong, 1.5～6 parts of Rhizoma Dioscoreae, Herba Epimedii 1.5～6
Part, 1.5～6 parts of compositions of Radix Polygalae.Although said medicine preparation has different degrees of therapeutical effect to old dementia patients, should
Class compound recipe is difficult to carry out industrialization, particularly in industrialized great production, due to flavour of a drug quantity excessively, it is difficult to control its impurity contain
Amount, it is difficult to effectively keep the stability of product, it is ensured that its product quality.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition for treating cognitive dysfunction, the pharmaceutical composition is by Huang
Stilbene, Radix Scutellariae, Rhizoma Alismatis, Radix Salviae Miltiorrhizae and Radix Ginseng are constituted.
Purposes of the pharmaceutical composition of the present invention in treatment Alzheimer disease drugs are prepared.
Pharmaceutical composition of the present invention improves the purposes in sugar metabolism levels medicine in treatment Alzheimer is prepared.
Pharmaceutical composition of the present invention improves intracerebral monoamine neurotransmitter and contains in treatment treatment Alzheimer is prepared
Purposes in amount medicine.
The intracerebral monoamine neurotransmitter is 5-HT, 5-HIAA, NE, DA.
Use after above-mentioned application of the present invention, it can be understood as the Radix Astragali, Radix Scutellariae, Rhizoma Alismatis, Radix Salviae Miltiorrhizae and Radix Ginseng combination and compatibility
In improve cognitive dysfunction, treatment Alzheimer, improve sugar metabolism levels, improve intracerebral monoamine neurotransmitters
Or it plays above-mentioned effect when with other drugs compatibility.
Another object of the present invention is to provide a kind of pharmaceutical composition for treating cognitive dysfunction, the medicine group
Compound is made up of Radix Astragali extract, Radix Scutellariae extract, Rhizoma Alismatis extract, Radix Salviae Miltiorrhizae extract and Radix Ginseng extract.
Purposes of the pharmaceutical composition of the present invention in treatment Alzheimer disease drugs are prepared.
Pharmaceutical composition of the present invention improves the purposes in sugar metabolism levels medicine in treatment Alzheimer is prepared.
Pharmaceutical composition of the present invention improves intracerebral monoamine neurotransmitter and contains in treatment treatment Alzheimer is prepared
Purposes in amount medicine.
The intracerebral monoamine neurotransmitter is 5-HT, 5-HIAA, NE, DA.
Above-mentioned application of the present invention, it can be understood as Radix Astragali extract, Radix Scutellariae extract, Rhizoma Alismatis extract, Radix Salviae Miltiorrhizae
It is used to improve cognitive dysfunction, treatment Alzheimer after extract and Radix Ginseng extract combination and compatibility, improves carbohydrate metabolism
Level, raising intracerebral monoamine neurotransmitters or the above-mentioned effect of its performance when with other drugs compatibility.
For clinical taking convenience, said medicine can directly be crushed or concentration is made and carried after conventional solvent is extracted
Take thing, pharmaceutical composition of the present invention can prepare piece agent, effervescent tablet, capsule, pill, powder, granule, syrup, oral
Liquid etc.；The freeze-dried powder used in parenteral administration and injection etc..
To enable above-mentioned dosage form to realize, pharmaceutically acceptable adjuvant need to be added when these dosage forms are prepared, for example：Filling
Agent, disintegrating agent, lubricant, suspending agent, binding agent, sweeting agent, correctivess, substrate etc..Filler includes：Starch, pregelatinated form sediment
Powder, Lactose, Mannitol, chitin, Microcrystalline Cellulose, sucrose etc.；Disintegrating agent includes：Starch, pregelatinized Starch, microcrystalline cellulose
Element, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, Croscarmellose Sodium etc.；Lubrication
Agent includes：Magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc.；Suspending agent includes：It is polyvinylpyrrolidone, micro-
Crystalline cellulose, sucrose, agar, hydroxypropyl methyl cellulose etc.；Binding agent includes, starch slurry, polyvinylpyrrolidone, hydroxypropyl
Methylcellulose etc.；Sweeting agent includes：Saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc.；Correctivess include：It is sweet
Taste agent and various essence；Substrate includes：Insect wax etc..
Radix Astragali extract of the present invention, Radix Scutellariae extract, Rhizoma Alismatis extract, Radix Salviae Miltiorrhizae extract and Radix Ginseng extract,
It prepares extracting method can appoint from water extraction, alcohol reflux, soak extraction, supersound extraction or seepage pressure effects etc. are conventional
A kind of method of anticipating is extracted；Further, can also purified, refinement treatment, such as mistake macroporous resin column after crude drug is extracted.
The Radix Astragali of the present invention is leguminous herbaceous plant's Radix Astagali, the root of Radix Astragali, and with tonifying Qi and lifting yang, consolidating superficial resistance stops
Antiperspirant, inducing diuresis to remove edema, blood-nourishing of promoting the production of body fluid, the stagnant blood stasis dispelling of row, expelling pus and toxin by strengthening QI, the effect of expelling pus and promoting granulation；The Radix Scutellariae is that labiate is yellow
The root of a kind of reed mentioned in ancient books, with heat clearing and damp drying, eliminating fire and detoxication, the effect of arresting bleeding and miscarriage prevention；The Rhizoma Alismatis are the dried pieces of Notes On Alism At Aceae Rhizoma Alismatis
Stem, with promoting diuresis to eliminate damp pathogen, expels the heat-evil, and changes the effect of turbid lipid-loweringing；The Radix Salviae Miltiorrhizae for dicotyledon Labiatae Radix Salviae Miltiorrhizae dry root and
Rhizome, with blood circulation promoting and blood stasis dispelling, inducing menstruation to relieve menalgia, relieving restlessness that clears away heart-fire, the effect of cool blood to disappear carbuncle；The Radix Ginseng is Araliaceae Radix Ginseng
Root, with strongly invigorating primordial QI, veins takes off admittedly, invigorating the spleen to benefit the lung, blood-nourishing of promoting the production of body fluid, the effect of tranquilize the mind and promote the intelligence.
Pharmaceutical composition of the present invention is through the beneficial effect that pharmacodynamicss are verified：Pharmaceutical composition of the present invention is by the Radix Astragali, Huang
A kind of reed mentioned in ancient books, Rhizoma Alismatis, Radix Salviae Miltiorrhizae and Radix Ginseng five kinds of Chinese medicine composition, Jing Model of Dementia mouse pharmacodynamic experiment proves that pharmaceutical composition of the present invention has
Preferable Anti-alzheimer's disease（Alzheimer）Effect.The present composition is by repetitious Pharmacodynamics screening reality
Test, compared with the Chinese medicine compound of anti-senile dementia in prior art, formula is more succinct, flavour of a drug quantity and medical material usage amount subtract
It is few, drug cost, but the middle recurrence due to taking drug of its clinical efficacy and prior art anti-senile dementia are decreased while economizing on resources
Side is close to, while the equal avirulence of medical material in pharmaceutical composition of the present invention, clinical application is safer.
Specific embodiment
Technical scheme is described in further detail with reference to specific embodiment, but protection scope of the present invention is not
It is confined to described below.
Embodiment 1
Raw material Radix Astragali 5g, Radix Scutellariae 5g, Rhizoma Alismatis 5g, Radix Salviae Miltiorrhizae 5g, Radix Ginseng 3g are weighed, raw material is directly crushed, according to conventional work
Skill adds customary pharmaceutical auxiliaries tabletting to obtain tablet.For improving cognitive dysfunction, treatment Alzheimer, improving sugared generation
Thank to level, improve intracerebral monoamine neurotransmitters.
Embodiment 2
Raw material Radix Astragali 10g, Radix Scutellariae 10g, Rhizoma Alismatis 10g, Radix Salviae Miltiorrhizae 10g, Radix Ginseng 5g are weighed, mixes 5 times of amounts of addition after each taste dense
The alcohol steep 24h for 95% is spent, extract A is concentrated under reduced pressure to give, medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 5 are added
Again 2h is decocted after the water immersion 1h of amount, decocted twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues reservation；S3：
The medicinal residues of S2 steps are dried, add 5 times to measure the alcohol steep 24h that concentration is 70%, be concentrated under reduced pressure to give extract C；S4：Will
Extract A, extract B and extract C are crushed, and add customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For changing
Kind cognitive dysfunction, treatment Alzheimer, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 3
Raw material Radix Astragali 20g, Radix Scutellariae 15g, Rhizoma Alismatis 15g, Radix Salviae Miltiorrhizae 15g, Radix Ginseng 10g are weighed, mixes 5 times of amounts of addition after each taste dense
The alcohol steep 20h for 70% is spent, extract A is concentrated under reduced pressure to give, medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 5 are added
Again 1.5h is decocted after the water immersion 1h of amount, decocted twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues reservation；
S3：The medicinal residues of S2 steps are dried, add 5 times to measure the alcohol steep 20h that concentration is 40%, be concentrated under reduced pressure to give extract C；S4：
Extract A, extract B and extract C are crushed, adds customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For
Improve cognitive dysfunction, treatment Alzheimer, improve sugar metabolism levels, improve intracerebral monoamine neurotransmitters.
Embodiment 4
Raw material Radix Astragali 25g, Radix Scutellariae 20g, Rhizoma Alismatis 20g, Radix Salviae Miltiorrhizae 20g, Radix Ginseng 15g are weighed, mixes 5 times of amounts of addition after each taste dense
The alcohol steep 20h for 75% is spent, extract A is concentrated under reduced pressure to give, medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 5 are added
Again 2h is decocted after the water immersion 1h of amount, decocted twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues reservation；S3：
The medicinal residues of S2 steps are dried, add 5 times to measure the alcohol steep 20h that concentration is 50%, be concentrated under reduced pressure to give extract C；S4：Will
Extract A, extract B and extract C are crushed, and add customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For changing
Kind cognitive dysfunction, treatment Alzheimer, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 5
Raw material Radix Astragali 15g, Radix Scutellariae 9g, Rhizoma Alismatis 9g, Radix Salviae Miltiorrhizae 9g, Radix Ginseng 6g are weighed, mixing 8 times of amount concentration of addition after each taste is
95% alcohol steep 24h, is concentrated under reduced pressure to give extract A, and medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 8 times of amounts are added
Water immersion 1h after decoct 2h, decoct twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues retain；S3：By S2
The medicinal residues of step are dried, and add 8 times to measure the alcohol steep 24h that concentration is 60%, are concentrated under reduced pressure to give extract C；S4：To extract
Thing A, extract B and extract C are crushed, and add customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.Recognize for improving
Know dysfunction, treatment Alzheimer, improve sugar metabolism levels, improve intracerebral monoamine neurotransmitters.
Embodiment 6
Raw material Radix Astragali 30g, Radix Scutellariae 25g, Rhizoma Alismatis 25g, Radix Salviae Miltiorrhizae 25g, Radix Ginseng 20g are weighed, mixes 8 times of amounts of addition after each taste dense
The alcohol steep 24h for 85% is spent, extract A is concentrated under reduced pressure to give, medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 8 are added
Again 2h is decocted after the water immersion 1h of amount, decocted twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues reservation；S3：
The medicinal residues of S2 steps are dried, add 8 times to measure the alcohol steep 24h that concentration is 60%, be concentrated under reduced pressure to give extract C；S4：Will
Extract A, extract B and extract C are crushed, and add customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For changing
Kind cognitive dysfunction, treatment Alzheimer, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 7
Raw material Radix Astragali 40g, Radix Scutellariae 30g, Rhizoma Alismatis 30g, Radix Salviae Miltiorrhizae 30g, Radix Ginseng 30g are weighed, mixes 6 times of amounts of addition after each taste dense
The alcohol steep 20h for 80% is spent, extract A is concentrated under reduced pressure to give, medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 6 are added
Again 2h is decocted after the water immersion 1h of amount, decocted twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues reservation；S3：
The medicinal residues of S2 steps are dried, add 6 times to measure the alcohol steep 20h that concentration is 65%, be concentrated under reduced pressure to give extract C；S4：Will
Extract A, extract B and extract C are crushed, and add customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For changing
Kind cognitive dysfunction, treatment Alzheimer, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 8
Raw material Radix Astragali 50g, Radix Scutellariae 40g, Rhizoma Alismatis 40g, Radix Salviae Miltiorrhizae 40g, Radix Ginseng 30g are weighed, mixes 6 times of amounts of addition after each taste dense
The alcohol steep 24h for 75% is spent, extract A is concentrated under reduced pressure to give, medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 6 are added
Again 2h is decocted after the water immersion 1h of amount, decocted twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues reservation；S3：
The medicinal residues of S2 steps are dried, add 6 times to measure the alcohol steep 24h that concentration is 50%, be concentrated under reduced pressure to give extract C；S4：Will
Extract A, extract B and extract C are crushed, and add customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For changing
Kind cognitive dysfunction, treatment Alzheimer, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 9
Raw material Radix Astragali 5g, Radix Scutellariae 5g, Rhizoma Alismatis 5g, Radix Salviae Miltiorrhizae 5g, Radix Ginseng 3g are weighed, adds 6 times of amounts dense after mixing ingredients
The alcohol steep 20h for 80% is spent, extract A is concentrated under reduced pressure to give, medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 5 are added
Again 2h is decocted after the water immersion 1h of amount, decocted twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues reservation；S3：
The medicinal residues of S2 steps are dried, add 6 times to measure the alcohol steep 24h that concentration is 50%, be concentrated under reduced pressure to give extract C；S4：Will
Extract A, extract B and extract C are crushed, and add customary pharmaceutical auxiliaries granulation to obtain granule according to common process.For
Improve cognitive dysfunction, treatment Alzheimer, improve sugar metabolism levels, improve intracerebral monoamine neurotransmitters.
Embodiment 10
Raw material Radix Astragali 10g, Radix Scutellariae 8g, Rhizoma Alismatis 8g, Radix Salviae Miltiorrhizae 8g, Radix Ginseng 5g are weighed, adds 8 times of amounts dense after mixing ingredients
The alcohol steep 24h for 85% is spent, extract A is concentrated under reduced pressure to give, medicinal residues retain；S2：The medicinal residues of S1 steps are dried, 8 are added
Again 2h is decocted after the water immersion 1h of amount, decocted twice, after merging decocting liquid twice, be concentrated to give extract B, medicinal residues reservation；S3：
The medicinal residues of S2 steps are dried, add 8 times to measure the alcohol steep 24h that concentration is 60%, be concentrated under reduced pressure to give extract C；S4：Will
Extract A, extract B and extract C are crushed, and add customary pharmaceutical auxiliaries granulation to obtain granule according to common process.For
Improve cognitive dysfunction, treatment Alzheimer, improve sugar metabolism levels, improve intracerebral monoamine neurotransmitters.
Embodiment 11
Raw material Radix Astragali 20g, Radix Scutellariae 12g, Rhizoma Alismatis 10g, Radix Salviae Miltiorrhizae 10g, Radix Ginseng 8g are weighed, raw material is directly crushed, according to normal
Rule technique adds customary pharmaceutical auxiliaries granulation to load capsule and obtains capsule.For improving cognitive dysfunction, treatment A Erci
The silent disease in sea, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 12
Raw material Radix Astragali 25g, Radix Scutellariae 15g, Rhizoma Alismatis 15g, Radix Salviae Miltiorrhizae 10g, Radix Ginseng 10g are weighed, raw material is directly crushed, according to normal
Rule technique adds customary pharmaceutical auxiliaries granulation to load capsule and obtains capsule.For improving cognitive dysfunction, treatment A Erci
The silent disease in sea, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 13
Raw material Radix Astragali 15g, Radix Scutellariae 9g, Rhizoma Alismatis 9g, Radix Salviae Miltiorrhizae 9g, Radix Ginseng 6g are weighed, according to common process conventional medicine is added
Adjuvant is prepared into oral liquid.For improving cognitive dysfunction, treatment Alzheimer, improving sugar metabolism levels, improve brain
Interior monoamine neurotransmitters.
Embodiment 14
Raw material Radix Astragali 30g, Radix Scutellariae 25g, Rhizoma Alismatis 25g, Radix Salviae Miltiorrhizae 25g, Radix Ginseng 20g are weighed, is added according to common process conventional
Excipient substance is prepared into oral liquid.For improving cognitive dysfunction, treatment Alzheimer, improving sugar metabolism levels, carry
High intracerebral monoamine neurotransmitters.
Embodiment 15
Raw material Radix Astragali extract 5g, Radix Scutellariae extract 5g, Rhizoma Alismatis extract 5g, Radix Salviae Miltiorrhizae extract 5g are weighed, Radix Ginseng is extracted
Thing 3g, raw material is directly crushed, and adds customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For improving cognitive function
Obstacle, treatment Alzheimer, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 16
Weigh raw material Radix Astragali extract 10g, Radix Scutellariae extract 10g, Rhizoma Alismatis extract 10g, Radix Salviae Miltiorrhizae extract 10g, Radix Ginseng
Extract 5g, raw material is directly crushed, and adds customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For improving cognition
Dysfunction, treatment Alzheimer, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 17
Weigh raw material Radix Astragali extract 20g, Radix Scutellariae extract 15g, Rhizoma Alismatis extract 15g, Radix Salviae Miltiorrhizae extract 15g, Radix Ginseng
Extract 10g, raw material is directly crushed, and adds customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.Recognize for improving
Know dysfunction, treatment Alzheimer, improve sugar metabolism levels, improve intracerebral monoamine neurotransmitters.
Embodiment 18
Weigh raw material Radix Astragali water extract 25g, Radix Scutellariae water extract 20g, Rhizoma Alismatis water extract 20g, Danshen
20g, Radix Ginseng water extract 15g, raw material is directly crushed, and adds customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.
Contain for improving cognitive dysfunction, treatment Alzheimer, improving sugar metabolism levels, raising intracerebral monoamine neurotransmitter
Amount.
Embodiment 19
Weigh raw material Radix Astragali water extract 15g, Radix Scutellariae water extract 9g, Rhizoma Alismatis water extract 9g, Danshen 9g,
Radix Ginseng water extract 6g, raw material is directly crushed, and adds customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.For changing
Kind cognitive dysfunction, treatment Alzheimer, raising sugar metabolism levels, raising intracerebral monoamine neurotransmitters.
Embodiment 20
Weigh raw material Radix Astragali extract 30g, Radix Scutellariae extract 25g, Rhizoma Alismatis extract 25g, Radix Salviae Miltiorrhizae extract 25g, Radix Ginseng
Extract 20g, raw material is directly crushed, and adds customary pharmaceutical auxiliaries tabletting to obtain tablet according to common process.Recognize for improving
Know dysfunction, treatment Alzheimer, improve sugar metabolism levels, improve intracerebral monoamine neurotransmitters.
Embodiment 21
Weigh raw material Radix Astragali ethanol extraction 40g, Radix Scutellariae ethanol extraction 30g, Rhizoma Alismatis ethanol extraction 30g, Radix Salviae Miltiorrhizae second
Alcohol extracting thing 30g, Radix Ginseng ethanol extraction 30g, raw material is directly crushed, and according to common process customary pharmaceutical auxiliaries tabletting is added
Obtain tablet.For improving cognitive dysfunction, treatment Alzheimer, improving sugar metabolism levels, improve intracerebral monoaminess
Neurotransmitter content.
Embodiment 22
Weigh raw material Radix Astragali ethanol extraction 50g, Radix Scutellariae ethanol extraction 40g, Rhizoma Alismatis ethanol extraction 40g, Radix Salviae Miltiorrhizae second
Alcohol extracting thing 40g, Radix Ginseng ethanol extraction 30g, raw material is directly crushed, and according to common process customary pharmaceutical auxiliaries tabletting is added
Obtain tablet.For improving cognitive dysfunction, treatment Alzheimer, improving sugar metabolism levels, improve intracerebral monoaminess
Neurotransmitter content.
Beneficial effects of the present invention are proved below by specific pharmacy test：
Pharmaceutical composition of the present invention is made up of the Radix Astragali, Radix Scutellariae, Rhizoma Alismatis, Radix Salviae Miltiorrhizae and Radix Ginseng five kinds of Chinese medicine, by experimental verification table
Bright each herbal medicine has different degrees of curative effect when being used alone to dementia mice, but is not enough to reach clinical efficacy, but logical
Crossing after combination and compatibility of the present invention can then reach preferable clinical efficacy, show that after compatibility, ingredients has Synergistic
Effect.
First, medicine antagonism scopolamine of the present invention causes to intend the test of dementia mice
1 experiment material
1.1 laboratory animal
KM mices 70,20 ± 2g of body weight, 45～50 days Mus ages, male and female half and half, by Sichuan Academy of Medical Sciences's experiment
Institute of Botany is provided, animal credit number：SCXK (river) 2008-24, in room temperature 22-24 DEG C, light and shade cycle 12h/12h conditions
Lower raising, free water is ingested.
1.2 medicines and reagent
Aricept（Donepezil Hydrochloride Tablets）, Wei Cai（China）Pharmaceutcal corporation, Ltd produces, lot number 120306.Hydrobromic acid east
Hyoscyami alkali liquor（SCOP）, Shanghai Hefeng Pharmaceutical Co., Ltd.'s production, lot number 6A18007.Biological work is built up in ACHE test kits, Nanjing
Journey institute, lot number 20120506.
1.3 experiment key instruments and reagent：
DT-200 mice diving tower testers（And test box）, Chengdu TME Technology Co., Ltd.；BA-200 keeps away dark survey automatically
Examination instrument（And test box）, Chengdu TME Technology Co., Ltd..
2 experimental techniques
2.1 packet and process
KM mices, male and female half and half are randomly divided into Normal group, model control group, Aricept positive by body weight and sex
Matched group, Chinese medicine compound matched group, the high, medium and low dosage group of medicine of the present invention, water extract group.
Chinese medicine compound matched group：The optimum proportioning announced using background technology ZL201010147176.1 embodiment and method
Prepare：Take Radix Astragali 1.5kg, Radix Polygoni Multiflori 1.5kg, Herba Epimedii 1.5kg, Fructus Alpiniae Oxyphyllae 1.2kg, Radix Salviae Miltiorrhizae 1.2kg, Radix Polygalae 0.9kg, Poria cum Radix Pini
0.9kg, Caulis Akebiae 0.9kg, Cortex Moutan 1.2kg, Rhizoma Chuanxiong 0.6kg, Rhizoma Acori Graminei 1.5kg, Rhizoma Alismatis 0.6kg, Radix Angelicae Pubescentiss 0.6kg, Radix Glycyrrhizae
0.9kg, Herba Menthae 0.45kg, Herba Schizonepetae 0.45kg, Radix Gentianae Macrophyllae 0.45kg, Radix Ginseng 0.45kg.6 times of amount decoctings are added to boil 2 ingredients
It is secondary, merge decocting liquid, it is configured to the medicinal liquid of 1g/ml.The preparation method of medicine middle dose group of the present invention is：According to embodiment 5
Prepared by dosage ratio and method, weigh raw material Radix Astragali 1.5kg, Radix Scutellariae 0.9kg, Rhizoma Alismatis 0.9kg, Radix Salviae Miltiorrhizae 0.9kg, Radix Ginseng 0.6kg,
Mix and add 8 times to measure the alcohol steep 24h that concentration is 95% after each taste, be concentrated under reduced pressure to give extract A, medicinal residues retain；S2：Will
The medicinal residues of S1 steps are dried, and after the water immersion 1h for adding 8 times of amounts 2h is decocted, and decoct twice, after merging decocting liquid twice, are concentrated to give
To extract B, medicinal residues reservation；S3：The medicinal residues of S2 steps are dried, add 8 times to measure the alcohol steep 24h that concentration is 60%, decompression
It is concentrated to give extract C；S4：By extract A, extract B and extract C, that is, the present composition is obtained, adds pure water,
It is configured to the medicinal liquid that concentration is 1g/ml.By 200ml concentration for 1g/ml concentration of liquid medicine into 100ml concentration for 2g/ml medicinal liquid,
As high dose administration group.By 50ml concentration for 1g/ml concentration of liquid medicine into 100ml concentration for 0.5g/ml medicinal liquid, it is as low
Dosed administration group.Water extract group of the present invention：Weigh raw material Radix Astragali water extract 15g, Radix Scutellariae water extract 9g, Rhizoma Alismatis water extraction
Thing 9g, Danshen 9g, Radix Ginseng water extract 6g after mixing each extract, adds pure water, is configured to concentration for 1g/
The medicinal liquid of ml.Each group animal presses the administration of 0.2ml/10g body weight/days ig.Dark, Jumping test group each group mice is kept away respectively at the 14th day
50min after administration, in addition to blank control group, remaining each group mice 10min before dark training, diving tower training is kept away, ip gives
SCOP2mg/kg body weight（0.1ml/10g body weight）, cause mouse memory acquired disturbance model.The N.S of blank control group ig equivalent.
Each group mice takes at once cerebral tissue in behavioristicss' off-test, prepares brain homogenate, determines each by the explanation of AchE test kits step
Mouse Whole Brain AchE is active for group.
2.2 ability of learning and memory in mice are tested
2.2.1 darkness avoidance test
（1）Keep away dark training：Dark test group mice is kept away after experiment ig administrations on the 14th or distilled water 50min, except blank right
Outer according to group, animal back is put into and keeps away the bright room of camera bellows by remaining each group ip in mice .SCOP modeling after 10min after modeling to hole, is adapted to
3min, leads to 36V alternating currents, and timing at once records the incubation period of each animal and errors number in 5min.
（2）Keep away dark test：Dark group mice is kept away in experiment the 15th day（After keeping away dark training 24 hours）Ig is administered or N.S60min
Afterwards, ibid mice is put into and keeps away the bright room of camera bellows by method, while logical 36V alternating currents, timing, record in 5min the incubation period of each animal and
Errors number.
2.2.2 step dow n test
（1）Diving tower is trained：Step down test group mice adopts and keeps away dark reality after experiment ig administrations on the 14th or N.S50min
Test identical method and make mouse memory acquired disturbance model, each group mice is put on diving tower after 10min, adapt to 3min, then give
32V alternating currents are given, at once timing, record the incubation period in animal 5min and errors number.
（2）Diving tower is tested：Diving tower group mice was in experiment the 15th day（After diving tower is trained 24 hours）, ig administration or N.S60min
Afterwards, ibid method is put in mice on diving tower, while giving 32V alternating currents and timing, records the incubation period in animal 5min and mistake
Miss number of times.
2.3 statistical procedures
Data statistics processing is carried out using SPSS15.0 statistical softwares.
3. result
The impact of 3.1 pairs of mice escape latencies and errors number（Darkness avoidance test）
Impact of the medicine of table 1 to mice escape latency and errors number（Darkness avoidance test）
Note：Compare with model group, * P<0.05；**P<0.01.
As shown in Table 1, compare with model control group, each dosage group of medicine, Aricept group can significantly extend hiding for mice
Phase（p<0.05）, and reduce the errors number of mice in 5min（p<0.05）, height of the invention, middle dose group, water extract group and
The curative effect of positive controls Aricept matched group is close to.The curative effect of high, middle dose group of the invention is slightly better than Chinese medicine compound matched group,
Low dose group is close to Chinese medicine compound matched group curative effect.
3.2 composition of prescription（SZ）Impact to mice escape latency and errors number（Step dow n test）
Impact of the medicament composing prescription of table 2 to mice escape latency and errors number（Step dow n test）
Note：Compare with model group, * P<0.05；**P<0.01.
As shown in Table 2, compare with model control group, the high, medium and low dosage group of medicine, Aricept matched group, water extract group
The incubation period of mice can significantly be extended（p<0.05）, and reduce the errors number of mice in 5min（p<0.05）, the present invention is high, in
Dosage group, water extract group and positive drug Aricept matched group curative effect are close to.During the high, curative effect of middle dose group of the invention is slightly better than
Recurrence due to taking drug side's matched group, low dose group is close to Chinese medicine compound matched group curative effect.
The impact of 3.3 pairs of memory acquisition disturbance Mice brain tissues AchE activity
The medicament composing prescription of table 3 causes the impact of dysmnesia model mice intracerebral AchE activity to SCOP
Note：Compare with model group,*P<0.05；**P<0.01.
From being shown in Table 3, compare with model control group, the high, medium and low dosage group of medicine, Aricept matched group, water extract
It is active that group can significantly reduce AchE（p<0.05）.The present invention is high, the curative effect of middle dose group is slightly better than Chinese medicine compound matched group, low dose
Amount group is close to Chinese medicine compound matched group curative effect.
4 conclusions
Pharmaceutical composition of the present invention can be significantly improved intend caused by scopolamine dementia mice ability of learning and memory, reduce brain group
Knit ACHE active, show that there is pharmaceutical composition of the present invention preferable dementia to act on.The present composition is compareed with Aricept
The curative effect of group is close to, and the curative effect of the present composition is slightly better than Chinese medicine compound matched group.
2nd, the impact that medicine of the present invention is expressed APP695 transgenic mice APP and A β
1. experiment material
Male APP695 transgenic mices, purchased from Institute of Experimental Animals, Chinese Academy of Medical Sciences, 30～35g of body weight, press
Body weight is randomly divided into model control group, Aricept positive controls, Chinese medicine compound matched group, the high, medium and low dosage of medicine of the present invention
Group, water extract group, the C57BL/6.I/J/ Mus processed without transgenic with the monthly age as Normal group, 8 per group.
2. experimental technique
2.1 medicine preparation
Chinese medicine compound matched group：The optimum proportioning announced using background technology ZL201010147176.1 embodiment and method
Prepare：Take Radix Astragali 1.5kg, Radix Polygoni Multiflori 1.5kg, Herba Epimedii 1.5kg, Fructus Alpiniae Oxyphyllae 1.2kg, Radix Salviae Miltiorrhizae 1.2kg, Radix Polygalae 0.9kg, Poria cum Radix Pini
0.9kg, Caulis Akebiae 0.9kg, Cortex Moutan 1.2kg, Rhizoma Chuanxiong 0.6kg, Rhizoma Acori Graminei 1.5kg, Rhizoma Alismatis 0.6kg, Radix Angelicae Pubescentiss 0.6kg, Radix Glycyrrhizae
0.9kg, Herba Menthae 0.45kg, Herba Schizonepetae 0.45kg, Radix Gentianae Macrophyllae 0.45kg, Radix Ginseng 0.45kg.6 times of amount decoctings are added to boil 2 ingredients
It is secondary, merge decocting liquid, it is configured to the medicinal liquid of 1g/ml.The preparation method of medicine middle dose group of the present invention is：According to embodiment 5
Prepared by dosage ratio and method, weigh raw material Radix Astragali 1.5kg, Radix Scutellariae 0.9kg, Rhizoma Alismatis 0.9kg, Radix Salviae Miltiorrhizae 0.9kg, Radix Ginseng 0.6kg,
Mix and add 8 times to measure the alcohol steep 24h that concentration is 95% after each taste, be concentrated under reduced pressure to give extract A, medicinal residues retain；S2：Will
The medicinal residues of S1 steps are dried, and after the water immersion 1h for adding 8 times of amounts 2h is decocted, and decoct twice, after merging decocting liquid twice, are concentrated to give
To extract B, medicinal residues reservation；S3：The medicinal residues of S2 steps are dried, add 8 times to measure the alcohol steep 24h that concentration is 60%, decompression
It is concentrated to give extract C；S4：By extract A, extract B and extract C, that is, the present composition is obtained, adds pure water,
It is configured to the medicinal liquid that concentration is 1g/ml.By 200ml concentration for 1g/ml concentration of liquid medicine into 100ml concentration for 2g/ml medicinal liquid,
As high dose administration group.By 50ml concentration for 1g/ml concentration of liquid medicine into 100ml concentration for 0.5g/ml medicinal liquid, it is as low
Dosed administration group.Water extract group of the present invention：Weigh raw material Radix Astragali water extract 15g, Radix Scutellariae water extract 9g, Rhizoma Alismatis water extraction
Thing 9g, Danshen 9g, Radix Ginseng water extract 6g after mixing each extract, adds pure water, is configured to concentration for 1g/
The medicinal liquid of ml.Each group animal presses the administration of 0.2ml/10g body weight/days ig.Blank is administered the distilled water gavage of same volume, respectively
The co-continuous gavage of group 15 days.
2.2 Testing index are drawn materials
Extract cerebrospinal fluid：Mice is Jing after last Behavior test, and 10% chloral hydrate (4ml/kg) intraperitoneal injection of anesthesia is little
Mus, at its rear portion a longitudinal incision is cooked, and bites napex muscle broken, fully exposure ring pillow caudacoria, and with blood taking needle ring pillow caudacoria is punctured,
The needle body is close to ring pillow caudacoria in case puncturing the blood vessel of lower section, extracts limpid cerebrospinal fluid about 5uL, and with the PBS of 0.lmol/L 10 are diluted
- 70 DEG C of preservations again.
Take brain：3 mices are randomly selected per group and does SABC, few Mus extract and directly break end after cerebrospinal fluid, then in ice
On quickly take brain, immediately input containing 8% paraformaldehyde solution in fix one week " the Jing gradients 70% with after, 80%, 90%, 95%,
100% ethanol is routinely dehydrated, wherein 95%, dehydration 1 time in dehydration 2 times, remaining each concentration ethanol in 100% ethanol is all de-
The water time is 2 hours, and dimethylbenzene is transparent, paraffin embedding.
Immunohistochemical method：Using immunohistochemical ABC method, the test kit of SP immunohistochemical 9002, PBS, citric acid are delayed
Liquid, DAB colour reagents box are rushed purchased from Bioisystech Co., Ltd of Zhong Shan Golden Bridge.(exempt from anti-APP, A β 1-40, A β -42 antibody to be purchased from
Beijing doctor's moral Bioisystech Co., Ltd.Concrete operation method is carried out according to kit specification.
Cerebral tissue BCA quantification of protein：BCA quantification of protein and RIPA whole proteins lysate are purchased from Puli's lema gene technology
Company limited.Mice extracts and directly breaks end after cerebrospinal fluid, and brain, liquid nitrogen quick freezing, -70 DEG C of preservations are then quickly taken on ice.
The RIPA whole protein lysates that cerebral tissue adds 5 times of volumes, 4 DEG C of homogenate cracking on ice are taken before measure.4 DEG C of 12000RPM centrifugations 20
Minute, collection supernatant effect BCA methods do protein quantification " to be initially set up standard curve, if the hole of gauge orifice 8, adds in every hole
Sample diluting liquid 100ul, the first hole adds standard substance 100ul, and 100ul is suctioned out with sample injector after mixing, moves to the second hole, so anti-
Oppose again and be diluted to seven apertures in the human head again, finally 100ul is suctioned out from seven apertures in the human head and discarded, be allowed to volume and be 100ul.Octal is sky
Compare in vain, remaining hole adds testing sample, and set multiple holes and compare.Optical density value is determined in 562nm, standard is finally calculated bent
Line, according to standard curve the protein concentration of each cracking cerebral tissue supernatant is calculated.
ELISA method quantitative determines cerebral tissue and cerebrospinal fluid A β -42 contents：Agent box is purchased from the limited public affairs of Kang Yuan Ruides biotechnology
Department, is detected according to test kit.Corresponding A β -42 contents are found on the graph according to sample 0D values, further according to dilution
Multiple calculates the content of each sample A β -42.
Statistical procedures：SABC randomly selects 3 mices per group, chooses same profile and cuts into slices 3, in optical microphotograph
Under mirror（10×40）Respectively choosing 6 visuals field per a section bilateral cortex and Hippocampal CA 1 same area respectively, record respectively
Accumulation optical density (the Integrated optical Density IOD) value in each visual field in selected each area, then ties each group analysis
Fruit and ELISA detection datas result carry out one factor analysis of variance between group with SPSS15.0 statistical softwares, as a result with mean ± mark
Quasi- difference is representedP<0.05 is have significant difference.
3. experimental result
The impact of 3.1 each group cerebral cortex and accumulative optical density IOD of CA1 areas APP positive cells
The each group cerebral cortex of table 4 and accumulative optical density IOD of CA1 areas APP positive cells
Note：Compare with model group, * P<0.05；**P<0.01.
As shown in Table 4, the IOD values of cerebral cortex and Hippocampal CA 1 are significantly raised after mice modeling, using medicine of the present invention
After each dosage group treatment, the IOD values of Cerebral Cortex and Hippocampal CA 1 have different degrees of reduction.With Aricept matched group
Compare, the present invention is high, the IOD value reductions of middle dose group and water extract group to Cerebral Cortex are closer to；It is of the invention high
Dosage group is closer to the IOD value reduction degree of CA 1 Zone of Hippocampus in Mouse with Aricept matched group.With Chinese medicine compound matched group phase
Than the present invention is high, the IOD values reduction effect of middle dose group and water extract group to Cerebral Cortex is substantially better than middle recurrence due to taking drug
Square matched group, the present invention is high, middle dose group is substantially better than Chinese medicine compound control to the IOD value reduction degree of CA 1 Zone of Hippocampus in Mouse
Group, water extract group is closer to the curative effect of Chinese medicine compound matched group.
The impact of 3.2 each group cerebral cortex and the accumulative optical density IOD value of CA1 areas A β -40 positive cells
The each group cerebral cortex of table 5 and accumulative optical density IOD of CA1 areas A β -40 positive cells
Note：Compare with model group, * P<0.05；**P<0.01.
As shown in Table 5, the accumulative optical density IOD value of A β -40 positive cells of cerebral cortex and Hippocampal CA 1 after mice modeling
It is significantly raised, after each dosage group treatment of medicine of the present invention, A β -40 positive cells of Cerebral Cortex and Hippocampal CA 1
Accumulative optical density IOD value has different degrees of reduction.Compared with Aricept matched group, the present invention is high, middle dose group is big to mice
The IOD values reduction effect of cortex A β -40 is slightly better than Aricept matched group, compared with Chinese medicine compound matched group, the present invention is high, in
IOD value reduction effect of the dosage group to Cerebral Cortex A β -40 is substantially better than Chinese medicine compound matched group.With Aricept matched group
Compare, IOD value reduction effect of the high dose group of the present invention to CA 1 Zone of Hippocampus in Mouse A β -40 is slightly better than Aricept matched group, with
Recurrence due to taking drug side's matched group is compared, and high dose group of the present invention is substantially better than Chinese medicine compound matched group.Water extract group mice of the present invention is big
The accumulative optical density IOD value reduction level of A β -40 positive cells of cortex and Hippocampal CA 1 is substantially better than Chinese medicine compound control
Group.
The impact of 3.3 each group cerebral cortex and the accumulative optical density IOD value of CA1 areas A β -42 positive cells
The each group cerebral cortex of table 6 and the accumulative optical density IOD value of Hippocampus blood capillary area A β -42 positive cells
As shown in Table 6, the accumulative light of A β -42 positive cells in cerebral cortex and Hippocampus Hippocampus blood capillary area is close after mice modeling
Degree IOD values are significantly raised, after being treated using each dosage group of medicine of the present invention, Cerebral Cortex and Hippocampus Hippocampus blood capillary area
The accumulative optical density IOD value of A β -42 positive cells has different degrees of reduction.High, middle dose group of the invention and water extract group drop
The level of the accumulative optical density IOD value of A β -42 positive cells in low cerebral cortex and Hippocampus Hippocampus blood capillary area is substantially better than Chinese medicine
Compound recipe matched group.
Above-mentioned experiment shows that pharmaceutical composition of the present invention and water extract can suppress APP, A β -40 in cerebral tissue, A β -42
Expression, show that pharmaceutical composition of the present invention and water extract can improve learning and memory function, to Alzheimer have compared with
Good therapeutical effect.
3rd, impact of the medicine of the present invention to Senescence-accelerated mice intracerebral monoamine neurotransmitters
1. experiment material
1.1 laboratory animal
Experiment is from 7 monthly age SAM series Senescence-accelerated Mouse's 80, male and female half and half, body weight 25-35g.By Chengdu Chinese medicine
University's Experimental Animal Center is provided.Model control group, Aricept positive controls, Chinese medicine compound control are randomly divided into by body weight
Group, the high, medium and low dosage group of medicine of the present invention, water extract group, 10 per group.
1.2 experimental apparatus
542 type automatic samplers, CH150 type column ovens, 582 type binary pumps, ACH-3（5μm,150mm×3mmID）Chromatography
Immobilized enzyme reactor, the 5600A type electrochemical detectors of coulomb array II, 5040 types after immobilized enzyme reactor, post before post, post
Solid microporous electricity level（Platinum electrode, solid-state palladium electrode）：ESA companies, the U.S..Ultrapure water purification system：Purelab Plus companies,
The U.S..Hypervelocity refrigerated centrifuge：55P-72 types, Hitachi, Ltd, Japan.- 80 DEG C of refrigerators：VXE380 types, Jouan companies, France.
1.3 experimental drug
4-hydroxy-3-methoxy-.alpha.-toluic acid.（Homovanillic acid, HVA）, disodium hydrogen phosphate（Na2HPO4）, tetramethyl ammonium chloride
（Tetramethylammonium chloride, TMACl）, sodium octyl（octanesulfonicacid
Sodiumsalt, OSA）, chlorination ACh, NE, DA, 2,4- dihydroxy acetic acid（Dihydroxyphenylacetic acid,
DOPAC）, 5-HT, 5-hydroxyindoleacetic acid（5-hydroxyindole acetic acid, 5-HIAA）, sodium dihydrogen phosphate
（NaH2PO4）, citric acid, sodium thiosulfate（Na2S2O5）, ethylenediaminetetraacetic acid（Ethylenediaminetetracetate,
EDTA）、Aβ1-40（HPLC levels）：Sigma companies, the U.S..Phosphoric acid (85%), perchloric acid, acetonitrile（HPLC levels）：Fisher
Scientific companies, the U.S.." MB " reagent：ESA companies, the U.S..
2. experimental technique
2.1 medicine preparation
Medication group converts according to clinical treatment dosage, and drug administration dosage of the present invention is Mouse Weight 200mg/kg,
Dosage is 0.2ml/10g body weight.Chinese medicine compound matched group is prepared according to the method for experiment one, and Aricept dosage is little
Mus body weight 0.58mg/kg, continuous gavage is administered 90 days, model group and Normal group in addition to the normal saline of gavage equivalent, its
It processes identical with each group.
2.2 Testing index are drawn materials
Gavage quick brain aging Mus sacrificed by decapitation after terminating, takes out rapidly full brain on ice platform, weigh, liquid nitrogen quick freezing ,-
80 DEG C of preservations.Full brain is put in ice-cold 0.1mol/L perchloric acid and is homogenized 20s during extraction（Perchloric acid 1mL is added again per 0.1g brains）.
Contain 0.04% in perchloric acid（w/v）Na2S2O5 and 0.04%（w/v）EDTA.Brain homogenate is in 4 DEG C of centrifugations（14000×g）20min.On
Clear liquid is filtered with 0.2 μm of filter membrane, subpackage, -80 DEG C of cold preservations, is detected for monoamine transmitterses and its metabolite.
Mobile phase：
NaH2PO4：90mmol/L；Citric acid：50mmol/L；OSA：1.7mmol/L；Acetonitrile：10%；
EDTA：100μmol/L；NaH2PO4, citric acid and OSA add 0.45 μm of Jing to have Jing after 0.2 μm of water system membrane filtration
The acetonitrile that machine mesentery is filtered, adds EDTA, and ionized water constant volume is boiled off again.
Chromatographic condition：Binary pump system：ESA582 types；Chromatographic column：C18,150 × 4.6mm, 5 μm；
Sample size：10μL；Flow velocity：0.6mL/min；Column temperature：Room temperature
Testing conditions：Detector：5600A type electrochemical detectors；Electrode：M5040 type analysis electrodes
Potential：- 150 ,+450 ,+500 ,+550mV
It is prepared by outer target：Weigh the HClO4 that each 10mg of NE, DOPAC, DA, 5-HIAA, HVA, 5-HT is dissolved in 100mL0.1M
It is middle as storing solution（100μg/mL）, subpackage, in being stored in -80 DEG C of refrigerators.Take storing solution（100μg/mL）1mL, is settled to 10mL,
Concentration is 10 μ g/mL.Diluent 0.5,0.4,0.3,0.2,0.1mL is taken, 0.1MHClO4 to 10mL is separately added into, be made into 500,
400th, 300, the 200, hybrid standard liquid of 100ng/mL.
3. experimental result
Compare with blank group, the content of model group 5-HT, 5-HIAA, DA and NE is substantially reduced, with statistical significance.Jing
After crossing Drug therapy of the present invention, the content of 5-HT, 5-HIAA, DA and NE has rising in various degree.The results are shown in Table 7.
The change of Hippocampus 5-HT, 5-HIAA, NE, DA in each group mouse brain of table 7（mmol/L,）
Note：Compare * P ＜ 0.05, * * P ＜ 0.01 with model group；
It is above-mentioned test result indicate that, pharmaceutical composition of the present invention can improve sugar metabolism levels in Alzheimer, can
The content of intracerebral monoamine neurotransmitter in improve Alzheimer.
Pharmaceutical composition of the present invention is made up of the Radix Astragali, Radix Scutellariae, Rhizoma Alismatis, Radix Salviae Miltiorrhizae and Radix Ginseng five kinds of Chinese medicine, and positive control drug is adopted
The Chinese medicine compound that Aricept and prior art are announced carries out comparative study, and the Chinese medicine compound is by the Radix Astragali, Rhizoma Alismatis, Cortex Moutan, Radix Ginseng, head
Crow, Herba Epimedii, Fructus Alpiniae Oxyphyllae, Radix Salviae Miltiorrhizae, Radix Polygalae, Poria cum Radix Pini, Caulis Akebiae, Rhizoma Chuanxiong, Rhizoma Acori Graminei, Radix Angelicae Pubescentiss, Radix Glycyrrhizae, Herba Menthae, Herba Schizonepetae and Radix Gentianae Macrophyllae group
Into.Medicine of the present invention compared with prior art Chinese medicine compound, Huang of the medicine of the present invention in prior art Chinese medicine compound is remained
Stilbene, Rhizoma Alismatis, Radix Salviae Miltiorrhizae and Radix Ginseng four Chinese medicine thing, eliminate the Radix Polygoni Multiflori, Herba Epimedii, Fructus Alpiniae Oxyphyllae, Radix Salviae Miltiorrhizae, Radix Polygalae, Poria cum Radix Pini, Caulis Akebiae, Rhizoma Chuanxiong,
Rhizoma Acori Graminei, Radix Angelicae Pubescentiss, Radix Glycyrrhizae, Herba Menthae, Herba Schizonepetae and Radix Gentianae Macrophyllae.After being experimentally confirmed the Radix Astragali and the Radix Astragali, Rhizoma Alismatis, Radix Salviae Miltiorrhizae and ginseng compatibility
Curative effect better than the curative effect of prior art Chinese medicine compound, be close to the curative effect of positive control drug Aricept.
In addition, containing nephrotoxicity medical material Caulis Akebiae in the Chinese medicine compound of prior art, pharmaceutical composition of the present invention is then removed
Nephrotoxicity medical material Caulis Akebiae in former side so that the present composition is safer in clinical application.
Claims (8)
1. a kind of pharmaceutical composition for treating cognitive dysfunction, it is characterised in that：Described pharmaceutical composition by the Radix Astragali, Radix Scutellariae,
Rhizoma Alismatis, Radix Salviae Miltiorrhizae and Radix Ginseng are constituted, wherein 15 parts of the Radix Astragali, 9 parts of Radix Scutellariae, 9 parts of Rhizoma Alismatis, 9 parts of Radix Salviae Miltiorrhizae, 6 parts of Radix Ginseng.
2. application of the pharmaceutical composition as claimed in claim 1 in treatment Alzheimer disease drugs are prepared.
3. pharmaceutical composition as claimed in claim 1 improves intracerebral monoaminess nerve and passs in treatment Alzheimer is prepared
Application in matter content medicine.
4. purposes as claimed in claim 3, wherein intracerebral monoamine neurotransmitter are 5-HT, 5-HIAA, NE, DA.
5. a kind of pharmaceutical composition for treating cognitive dysfunction, it is characterised in that：Described pharmaceutical composition is by Radix Astragali water extraction
Thing, Radix Scutellariae water extract, Rhizoma Alismatis water extract, Danshen and Radix Ginseng water extract are constituted, wherein Radix Astragali water extract
15 parts, 9 parts of Radix Scutellariae water extract, 9 parts of Rhizoma Alismatis water extract, 9 parts of Danshen, 6 parts of Radix Ginseng water extract.
6. application of the pharmaceutical composition as claimed in claim 5 in treatment Alzheimer disease drugs are prepared.
7. pharmaceutical composition as claimed in claim 5 improves intracerebral monoaminess nerve and passs in treatment Alzheimer is prepared
Application in matter content medicine.
8. purposes as claimed in claim 7, wherein intracerebral monoamine neurotransmitter are 5-HT, 5-HIAA, NE, DA.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310487271.XA CN103566087B (en) | 2013-10-17 | 2013-10-17 | Pharmaceutical composition for treating cognitive disorder and application thereof in preparation of medicine for treating Alzheimer disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310487271.XA CN103566087B (en) | 2013-10-17 | 2013-10-17 | Pharmaceutical composition for treating cognitive disorder and application thereof in preparation of medicine for treating Alzheimer disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103566087A CN103566087A (en) | 2014-02-12 |
| CN103566087B true CN103566087B (en) | 2017-04-12 |
Family
ID=50039368
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310487271.XA Active CN103566087B (en) | 2013-10-17 | 2013-10-17 | Pharmaceutical composition for treating cognitive disorder and application thereof in preparation of medicine for treating Alzheimer disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103566087B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114129696A (en) * | 2014-05-21 | 2022-03-04 | 青州市杏林春膏贴科学研究所 | Composition for preventing and treating senile dementia and preparation method and application thereof |
| CN105664030A (en) * | 2016-02-22 | 2016-06-15 | 霍清萍 | Traditional Chinese medicine composition for improving cerebral small vessel disease cognition impairment and preparation method and application thereof |
| CN110824048B (en) * | 2019-11-14 | 2022-05-13 | 美国琛蓝营养制品股份有限公司 | Method for establishing fingerprint of traditional Chinese medicine compound or preparation thereof with cognitive improvement effect |
| CN115120660B (en) * | 2022-04-11 | 2023-06-16 | 中国中医科学院医学实验中心 | Chinese medicinal composition for preventing and/or treating Parkinson disease, application thereof, pill and tablet |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179741C (en) * | 2002-04-26 | 2004-12-15 | 林宝婉 | Compound Chinese medicine for treating cerebrovascular disease |
| CN101797351B (en) * | 2010-04-15 | 2012-06-06 | 曾淑纯 | Traditional Chinese medicine for preventing senile dementia |
| CN103127286A (en) * | 2011-12-05 | 2013-06-05 | 鲍力恒 | Medicine component used for curing or lightening melancholia or neurodegeneration disease |
| CN102716459B (en) * | 2012-05-08 | 2014-06-18 | 四川中方制药有限公司 | Chinese medicinal composition for treating senile mild cognitive impairment and preparation method thereof |
| CN103127466B (en) * | 2013-02-03 | 2014-10-29 | 于占彩 | Chinese medicine decoction for treating cognitive disorder of Parkinson disease |
-
2013
- 2013-10-17 CN CN201310487271.XA patent/CN103566087B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN103566087A (en) | 2014-02-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104645091A (en) | Capsule for treating hypertension | |
| CN100404035C (en) | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease | |
| CN100522212C (en) | Traditional Chinese medicine composition for treating depression and its preparing method | |
| CN103566087B (en) | Pharmaceutical composition for treating cognitive disorder and application thereof in preparation of medicine for treating Alzheimer disease | |
| JP7460204B2 (en) | Herbal compound preparation for treating Parkinson's disease and its manufacturing method and use | |
| CN1524542A (en) | Medicament for treating acute and chronic rhinitis and nasosinusitis | |
| CN101869600A (en) | Medicinal composition for treating degenerative change in central nervous system, preparation method and application thereof | |
| CN103520293A (en) | Oral traditional Chinese medicine for improving and treating constipation | |
| CN101069734B (en) | Chinese medicine composition for vascular cretinism and preparing method therefor | |
| CN101095900B (en) | Sichuan chrysanthemum pain-relieving capsule and method for preparing the same | |
| CN102488838B (en) | Traditional Chinese medicine composition used for treating viral myocarditis | |
| CN103108639B (en) | Composition of active ingredient of traditional chinese medicine and use thereof | |
| CN101677989A (en) | A drug composition for treatment and prevention of ischemic stroke and its preparation methods | |
| CN1883533A (en) | Pharmaceutical composition for treating apoplexy and preparation method thereof | |
| CN104771652A (en) | Vertigo treating traditional Chinese medicine composition | |
| CN108514582A (en) | A kind of component compatibility Chinese medicine of prevention Alzheimer disease | |
| CN104707023A (en) | Traditional Chinese medicinal composition for treating polycystic ovary syndrome, and preparation method thereof | |
| CN103157067A (en) | Traditional Chinese medicine preparation for treating trigeminal neuralgia | |
| CN108143800B (en) | Traditional Chinese medicine composition for treating hypertensive heart failure | |
| CN105727089A (en) | Application of medicine composition containing folium artemisiae argyi to preparing medicine for treating irritable bowel syndrome | |
| CN105079328A (en) | Chinese herb composition for treating epistaxis | |
| CN104758588A (en) | Traditional Chinese medicine composition for treating dizziness | |
| CN105853759A (en) | Traditional Chinese medicine composition, its extract product, its preparation, preparation method and application thereof | |
| CN105617251A (en) | Traditional Chinese medicine composition for treating depression and preparation method thereof | |
| CN103585495A (en) | Capsule for treating diabetic kidney damage |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220718 Address after: 276006 No. 209 Hongqi Road, Shandong, Linyi Patentee after: LUNAN PHARMACEUTICAL Group Corp. Address before: 075000 Room 201, unit 4, building 8, beierdao lane, Shuncheng Street, Xuanhua District, Zhangjiakou City, Hebei Province Patentee before: Yutejin |
|
| TR01 | Transfer of patent right |