CN110201118A - A kind of Chinese medicine composition treats or prevents the application in vascular senile dementia drug in preparation - Google Patents
A kind of Chinese medicine composition treats or prevents the application in vascular senile dementia drug in preparation Download PDFInfo
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Abstract
The present invention relates to technical field of traditional Chinese medicines, in particular to a kind of Chinese medicine composition treats or prevents the application in vascular senile dementia drug in preparation.The Chinese medicine composition is made of Radix Salviae Miltiorrhizae, Radix Notoginseng, safflower, Herba Epimedii, Pachyrhizua angulatus, Radix Curcumae, peach kernel, Rhizoma Chuanxiong, leech, borneol, Moschus, ginseng stem and leave general saponin.The traditional chinese medicine composition of the invention can be obviously improved vascular dementia rats spatial cognition memory capability and exploratory behavior, play neuroprotection mechanism may it is anti-inflammatory to its, antioxidant stress injury effect is clear related.And apparent advantage function is also showed that compared with the comparative sample of prior art preparation.
Description
Technical field
The present invention relates to technical field of traditional Chinese medicines, in particular to a kind of Chinese medicine composition is old in preparation treatment or prevention vascular
Application in dementia drug.
Background technique
In recent years, with the continuous aggravation of world population ages' degree, the incidence of this disease of vascular dementia
Increase year by year, vascular dementia (VD) is to be only second to the second lunacy of Alzheimer disease (Alzheimer ' s disease, AD)
Slow-witted disease.The normal life of the elderly has not only been seriously affected, but also has caused huge burden to family and society.Institute
With the treatment of vascular dementia (VD) also just becomes a big hot subject of contemporary medical science circle.
Having the pharmaceutical composition for the treatment of vascular dementia at present has very much, such as: authorization publication number CN109260260A is public
Open it is a kind of treat treating coronary heart disease and angina pectoris and preparation method thereof, the drug is by 1-3 parts of Moschus, 200-400 parts of Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae
200-400 parts, 5-15 parts of storax, 5-15 parts of borneol, 100-200 parts of nutmeg compositions.Authorize publication number CN 1679787A public
Chinese materia medica preparation for the treatment of vascular diseases and preparation method thereof and method of quality control are opened, Chinese materia medica preparation main component is pellet
Ginseng, Radix Notoginseng, safflower, Herba Epimedii, pueraria lobata, Radix Curcumae, borneol, Moschus, the capsule of ginseng stem and leave general saponin or soft capsule or dripping pill.It awards
Power 108853294 A of publication No. CN discloses a kind of drug composition and its preparation method and application for treating vascular dementia, by
The raw material of following weight proportion is prepared: 10-30 parts of Rhizoma Chuanxiong, 5-20 parts of Radix Angelicae Sinensis, 1-15 parts of radix scutellariae, 1-12 parts of rhizoma acori graminei, Fu
The bulk pharmaceutical chemicals such as 1-12 parts of Siberian cocklebur, 2-12 parts of Radix Polygalae, 1-12 parts of ginseng composition.Prescription flavour of a drug disclosed above are more, complicated component, it is difficult to
Control the quality of product.
Western medicine is mostly control cerebrovascular risk factor to the treatment method of VD, improves Brain circlulation, promotes brain metabolism, improving brain
Based on interior cruel choline levels of second etc., though improving Patients ' Cognitive and memory function to a certain extent, there are curative effects not significant, medicine
Object strong toxicity, the defects of side effect is more at present mainly have the treatment of VD the generation of prevention and treatment cerebral apoplexy, improve cognitive function,
Control mental symptom etc., but cannot effective reverse disease process.
Moschus heart sermion tablet main ingredient includes Radix Salviae Miltiorrhizae, Radix Notoginseng, safflower, Herba Epimedii, Pachyrhizua angulatus, Radix Curcumae, peach kernel, Rhizoma Chuanxiong, water
Leech, borneol, muscone, ginseng stem and leave general saponin.Cure mainly activating microcirculation and removing stasis medicinal, analgesic of having one's ideas straightened out, for apoplexy caused by obstruction of collaterals by blood stasis, in
Channels and collaterals and coronary heart diseases and angina pectoris, card are shown in: shouting pain uncomfortable in chest, facial paralysis, hemiplegia.Currently, there has been no this product to be applied to blood vessel
Property brain dementia in terms of study relevant report.
Summary of the invention
Vascular senile dementia drug is treated or prevented in preparation in view of this, the present invention provides a kind of Chinese medicine compositions
In application.The pharmaceutical composition can be obviously improved vascular dementia rats spatial cognition memory capability and exploratory behavior,
Play neuroprotection mechanism may, antioxidant stress injury anti-inflammatory to its effect it is clear related.
In order to achieve the above-mentioned object of the invention, the present invention the following technical schemes are provided:
The present invention provides a kind of Chinese medicine compositions to treat or prevent the application in vascular senile dementia drug in preparation,
Chinese medicine composition is by Radix Salviae Miltiorrhizae, Radix Notoginseng, safflower, Herba Epimedii, Pachyrhizua angulatus, Radix Curcumae, peach kernel, Rhizoma Chuanxiong, leech, borneol, Moschus, gen-seng haulms
Total saposins are made.
The diagnosis and treatment based on an overall analysis of the illness and the patient's condition such as Chinese medicine treatment use tonifies the liver and kidney, dissipating phlegm for resuscitation, activating microcirculation and removing stasis medicinal.This product traditionally " draw by medicine
Medicine human brain helps medicine uplink " theory, directly act on brain cell tissue, repair, activation is impaired and the brain cell of dormant state.
So this product has certain Action advantage in treatment vascular dementia.
Preferably, in parts by weight, Chinese medicine composition by 10~12 parts of Radix Salviae Miltiorrhizae, 0.5~1 part of Radix Notoginseng, 2~4 parts of safflower,
4~6 parts of Herba Epimedii, 4~6 parts of Pachyrhizua angulatus, 2~4 parts of Radix Curcumae, 9~12 parts of peach kernel, 1~3 part of Rhizoma Chuanxiong, 1~3 part of leech, borneol 0.1
~0.3 part, 0.005~0.01 part of Moschus, 0.05~0.1 part of ginseng stem and leave general saponin be made.
Preferably, in parts by weight, Chinese medicine composition is by 10 parts of Radix Salviae Miltiorrhizae, 0.5 part of Radix Notoginseng, 2.5 parts of safflower, Herba Epimedii 4
Part, 4 parts of Pachyrhizua angulatus, 2.5 parts of Radix Curcumae, 9.8 parts of peach kernel, 1 part of Rhizoma Chuanxiong, 1.3 parts of leech, 0.1 part of borneol, 0.008 part of Moschus, ginseng
0.08 part of stem-leaf total saponin is made.
Preferably, the preparation method of the Chinese medicine composition includes the following steps:
(1) leech is crushed, adds the water of 8~12 times of weight, be homogenized, impregnated, filtration；Take filter residue, then plus 3~5 times of weight
Water, be homogenized, impregnate, filtration；Merging filtrate, centrifugation, takes supernatant, obtains medical fluid A；
(2) Radix Salviae Miltiorrhizae, safflower, peach kernel, Pachyrhizua angulatus, Rhizoma Chuanxiong, Radix Curcumae, Herba Epimedii are taken, is crushed, the water of 6~10 times of weight is added,
It impregnates, refluxing extraction, Aqueous extracts filtration obtains medical liquid B；
(3) medical fluid A merges with medical liquid B, and concentration is dried under reduced pressure, obtains extract A；
(4) Radix Notoginseng is crushed, the ethanol water refluxing extraction of 8~10 times of weight is added, ethyl alcohol, decompression are recycled in filtration
Concentration, is splined on macroreticular resin, successively passes through water, 30% ethyl alcohol, 70% ethanol elution, collects 70% ethanol eluate, is concentrated,
It is dried under reduced pressure, obtains arasaponin；
(5) extract A, arasaponin, borneol, Moschus, ginseng stem and leave general saponin are crushed, is uniformly mixed.
In embodiment provided by the invention, step (1) are as follows: leech is crushed, the water of 8 times of weight is added, is homogenized, is impregnated,
Filtration；Take filter residue, then plus 3 times of weight water, be homogenized, impregnate, filtration；Merging filtrate, centrifugation, takes supernatant, obtains medical fluid A.
Preferably, the temperature of immersion is 0~8 DEG C in step (1), the time of immersion is 10~14 hours；Homogenate when
Between be 30~60 minutes；The revolving speed of centrifugation is 3000~5000r/min, and the time of centrifugation is 5~10 minutes.
Preferably, in step (1), the temperature of immersion is 4 DEG C, and the time of immersion is 12 hours；The time of homogenate is 30 points
Clock；The revolving speed of centrifugation is 4000r/min, and the time of centrifugation is 5 minutes.
In embodiment provided by the invention, in step (2), Radix Salviae Miltiorrhizae, safflower, peach kernel, Pachyrhizua angulatus, Rhizoma Chuanxiong, Radix Curcumae, excessive sheep are taken
The leaves of pulse plants crushes, the water of 6 times of weight is added, and impregnates, refluxing extraction, and Aqueous extracts filtration obtains medical liquid B.
Preferably, the time of immersion is 0.5~2 hour in step (2), the time of each refluxing extraction is 1~3 small
When, the number of refluxing extraction is 2~3 times, Aqueous extracts filtration, merging filtrate.
Preferably, in step (2), the time of immersion is 0.5 hour, and the time of each refluxing extraction is 1 hour, reflux
The number of extraction is 3 times, Aqueous extracts filtration, merging filtrate.
Preferably, being concentrated into relative density 1.25~1.35 at 50 DEG C in step (3), the temperature being dried under reduced pressure is 40
~60 DEG C.
Preferably, in step (3), it is concentrated into relative density 1.25~1.35 at 50 DEG C, the temperature being dried under reduced pressure is 50 DEG C.
In embodiment provided by the invention, in step (4), Radix Notoginseng is crushed, the ethanol water that 8 times of weight is added returns
Stream extracts.
Preferably, the volumn concentration of ethanol water is 70%~80% in step (4).
Preferably, in step (4), the volumn concentration of ethanol water is 70%.
Preferably, the number of refluxing extraction is 2~3 times, every time 1~3 hour in step (4).
Preferably, in step (4), the number of refluxing extraction is 2 times, every time 2 hours.
Preferably, treating or preventing vascular senile dementia drug further includes pharmaceutically acceptable auxiliary material.
Preferably, the dosage form for treating or preventing vascular senile dementia drug is granule, tablet, capsule or dripping pill
Agent.
The present invention provides a kind of Chinese medicine compositions to treat or prevent the application in vascular senile dementia drug in preparation,
The Chinese medicine composition is by Radix Salviae Miltiorrhizae, Radix Notoginseng, safflower, Herba Epimedii, Pachyrhizua angulatus, Radix Curcumae, peach kernel, Rhizoma Chuanxiong, leech, borneol, Moschus, ginseng stem
Leaf total saposins are made.The technical effect that the present invention has are as follows:
The traditional chinese medicine composition of the invention can be obviously improved vascular dementia rats spatial cognition memory capability and exploratory behavior,
Its mechanism for playing neuroprotection may, antioxidant stress injury anti-inflammatory to its effect it is clear related.And the and prior art
The comparative sample of preparation relatively also shows that apparent advantage function.
The present invention, in conjunction with drug effect, determines compositions, process of the present invention by improving to existing prescription preparation process,
Improve mouthfeel, reduces dose, and with the obvious advantage in terms for the treatment of vascular dementia.
Specific embodiment
The invention discloses a kind of Chinese medicine compositions to treat or prevent the application in vascular senile dementia drug in preparation,
Those skilled in the art can use for reference present disclosure, be suitably modified realization of process parameters.In particular, it should be pointed out that all similar
Replacement and change it is apparent to those skilled in the art, they are considered as being included in the present invention.The present invention
Method and application be described by preferred embodiment, related personnel can obviously not depart from the content of present invention, essence
Method described herein and application are modified or appropriate changes and combinations in mind and range, carry out implementation and application skill of the present invention
Art.
The formula (weight ratio) of pharmaceutical composition of the present invention is as follows:
Radix Salviae Miltiorrhizae (10 parts -12 parts), Radix Notoginseng (0.5 part -1 part), safflower (2 parts -4 parts), Herba Epimedii (4 parts -6 parts), Pachyrhizua angulatus (4
Parts -6 parts), Radix Curcumae (2 parts -4 parts), peach kernel (9 parts -12 parts), Rhizoma Chuanxiong (1 part -3 parts), leech (1 part -3 parts), borneol (0.1 part -
0.3 part), muscone's (0.005 part -0.01 part), 12 taste Chinese medicinal composition of ginseng stem and leave general saponin (0.05 part -0.1 part).
Pharmaceutical composition of the present invention the preparation method is as follows:
(1) water intaking leech, is ground into coarse powder, adds 8-12 times of water, and high speed dispersion instrument is homogenized 30-60 minutes, adds water polishing to 8-
12 times amount, refrigerator place, impregnate 12 hours, filtration, filtrate is spare, then plus 3-5 times of water, high speed dispersion instrument be homogenized 30-60 minutes,
Water polishing is added to measure to 3-5 times, refrigerator is placed, and is impregnated 12 hours, filtration, merging filtrate, and low-speed centrifugal 4000r/min is centrifuged 5-
It 10 minutes, takes 4 DEG C of refrigerators of supernatant to save backup, obtains medical fluid A.
(2) Radix Salviae Miltiorrhizae, safflower, peach kernel, Pachyrhizua angulatus, Rhizoma Chuanxiong, Radix Curcumae, Herba Epimedii are taken, coarse powder is broken into, with 6~10 times of amount water, leaching
Bubble 0.5~2 hour, adds water refluxing extraction 2~3 times, 1-3 hours each, and Aqueous extracts filtration, merging filtrate obtains medical liquid B.
(3) medical fluid A merges with medical liquid B, is concentrated into relative density 1.25-1.35 at 50 DEG C, is dried under reduced pressure, obtains extract A.
(4) pseudo-ginseng is taken, coarse powder is ground into, 70~80% alcohol refluxs measured with 8~10 times extract 2 times, and every time 2
Hour, ethyl alcohol is recycled in filtration, is concentrated under reduced pressure, is splined on macroreticular resin, successively passes through water, 30%, 70% ethanol elution, collects
70% ethanol eluate, concentration, is dried under reduced pressure to get arasaponin.
(5) by extract A, arasaponin, borneol, muscone, ginseng stem and leave general saponin powder, it is ground into fine powder, is mixed
It closes uniformly, corresponding auxiliary material is added, the oral preparations such as granule, tablet, capsule, pill are made.
The utility model has the advantages that the present invention by improving to existing prescription preparation process, in conjunction with drug effect, determines present invention combination
Preparation method improves mouthfeel, reduces dose, and with the obvious advantage in terms for the treatment of vascular dementia.Advantage of the invention exists
In: the cumbersome and apparent toxic side effect of a large amount of Chinese medicines of traditional Chinese medicine compatibility is overcome, the hypoglycemic sample with prior art preparation
Compare and also shows that apparent advantage function.Medical value in terms of vascular dementia effect to facilitate the understanding of the present invention,
Show pharmaceutical composition of the present invention, specific embodiment is as follows:
Chinese medicine composition provided by the invention treats or prevents institute in the application in vascular senile dementia drug in preparation
It is available on the market with raw material or auxiliary material.
Below with reference to embodiment, the present invention is further explained:
Embodiment 1
The formula (weight ratio) of the present embodiment pharmaceutical composition is as follows:
10 parts of Radix Salviae Miltiorrhizae, 0.5 part of Radix Notoginseng, 2.5 parts of safflower, 4 parts of Herba Epimedii, 4 parts of Pachyrhizua angulatus, 2.5 parts of Radix Curcumae, 9.8 parts of peach kernel, river
0.08 part of 12 1 part of rhizome of chuanxiong, 1.3 parts of leech, 0.1 part of borneol, 0.008 part of Moschus, ginseng stem and leave general saponin taste Chinese medicinal composition.
The present embodiment pharmaceutical composition the preparation method is as follows:
(1) water intaking leech, is ground into coarse powder, adds 8 times of water, and high speed dispersion instrument is homogenized 30 minutes, adds water polishing to 8 times of amounts, ice
Case place, impregnate 12 hours, filtration, filtrate is spare, then plus 3 times of water, high speed dispersion instrument be homogenized 30 minutes, add water polishing to 3 times
Amount, refrigerator are placed, and are impregnated 12 hours, filtration, merging filtrate, and low-speed centrifugal 4000r/min is centrifuged 5 minutes, takes 4 DEG C of supernatant
Refrigerator saves backup, and obtains medical fluid A.
(2) Radix Salviae Miltiorrhizae, safflower, peach kernel, Pachyrhizua angulatus, Rhizoma Chuanxiong, Radix Curcumae, Herba Epimedii are taken, coarse powder is broken into, with 6 times of amount water, impregnates 0.5
Hour, add water refluxing extraction 3 times, 1 hour every time, Aqueous extracts filtration, merging filtrate obtained medical liquid B.
(3) medical fluid A merges with medical liquid B, is concentrated into relative density 1.25-1.35 (50 DEG C), and 50 DEG C are dried under reduced pressure, and must extract
Object A.
(4) pseudo-ginseng is taken, coarse powder is ground into, 70% alcohol reflux measured with 8 times extracts 2 times, 2 hours every time, filters
It crosses, recycles ethyl alcohol, be concentrated under reduced pressure, be splined on macroreticular resin, successively pass through water, 30%, 70% ethanol elution, collect 70% second
Alcohol eluen, concentration, is dried under reduced pressure to get arasaponin.
(5) by extract A, arasaponin, borneol, muscone, ginseng stem and leave general saponin powder, it is ground into fine powder, is mixed
It closes uniformly, is added 10 parts of sucrose, granule is made.
Embodiment 2:
The formula (weight ratio) of the present embodiment pharmaceutical composition is as follows:
12 parts of Radix Salviae Miltiorrhizae, 1 part of Radix Notoginseng, 4 parts of safflower, 6 parts of Herba Epimedii, 6 parts of Pachyrhizua angulatus, 4 parts of Radix Curcumae, 12 parts of peach kernel, 1 part of Rhizoma Chuanxiong,
0.1 part of 12 3 parts of leech, 0.3 part of borneol, 0.01 part of Moschus, ginseng stem and leave general saponin taste Chinese medicinal composition.
The present embodiment pharmaceutical composition the preparation method is as follows:
(1) it fetches water leech, is ground into coarse powder, adds 12 times of water, high speed dispersion instrument is homogenized 60 minutes, and add water polishing to measure to 12 times,
Refrigerator place, impregnate 12 hours, filtration, filtrate is spare, then plus 5 times of water, high speed dispersion instrument be homogenized 60 minutes, add water polishing to 5
It measures again, refrigerator is placed, and is impregnated 12 hours, filtration, merging filtrate, low-speed centrifugal 4000r/min, and centrifugation 10 minutes takes supernatant 4
DEG C refrigerator saves backup, and obtains medical fluid A.
(2) Radix Salviae Miltiorrhizae, safflower, peach kernel, Pachyrhizua angulatus, Rhizoma Chuanxiong, Radix Curcumae, Herba Epimedii are taken, coarse powder is broken into, with 10 times of amount water, impregnates 2
Hour, add water refluxing extraction 2 times, 3 hours every time, Aqueous extracts filtration, merging filtrate obtained medical liquid B.
(3) merge with medical fluid A, be concentrated into relative density 1.25-1.35 (50 DEG C), 60 DEG C are dried under reduced pressure, and obtain extract A.
(4) pseudo-ginseng is taken, coarse powder is ground into, 75% alcohol reflux measured with 10 times extracts 2 times, 2 hours every time, filters
It crosses, recycles ethyl alcohol, be concentrated under reduced pressure, be splined on macroreticular resin, successively pass through water, 30%, 70% ethanol elution, collect 70% second
Alcohol eluen, concentration, is dried under reduced pressure to get arasaponin.
(5) by extract A, arasaponin, borneol, muscone, ginseng stem and leave general saponin powder, it is ground into fine powder, is mixed
It closes uniformly, particle is made, Magnesium Stearate proper quantity is added, be uniformly mixed, tablet is made in tabletting.
Embodiment 3:
The formula (weight ratio) of the present embodiment pharmaceutical composition is as follows:
11 parts of Radix Salviae Miltiorrhizae, 0.8 part of Radix Notoginseng, 3 parts of safflower, 5 parts of Herba Epimedii, 5 parts of Pachyrhizua angulatus, 5 parts of Radix Curcumae, 12 parts of peach kernel, Rhizoma Chuanxiong 2
0.08 part of 12 part, 3 parts of leech, 0.3 part of borneol, 0.01 part of Moschus, ginseng stem and leave general saponin taste Chinese medicinal composition.
The present embodiment pharmaceutical composition the preparation method is as follows:
(1) it fetches water leech, is ground into coarse powder, adds 10 times of water, high speed dispersion instrument is homogenized 45 minutes, and add water polishing to measure to 10 times,
Refrigerator place, impregnate 12 hours, filtration, filtrate is spare, then plus 4 times of water, high speed dispersion instrument be homogenized 45 minutes, add water polishing to 4
It measures again, refrigerator is placed, and is impregnated 12 hours, filtration, merging filtrate, low-speed centrifugal 4000r/min, and centrifugation 5 minutes takes supernatant 4
DEG C refrigerator saves backup, and obtains medical fluid A.
(2) Radix Salviae Miltiorrhizae, safflower, peach kernel, Pachyrhizua angulatus, Rhizoma Chuanxiong, Radix Curcumae, Herba Epimedii are taken, coarse powder is broken into, with 8 times of amount water, it is small to impregnate 1
When, add water refluxing extraction 3 times, 2 hours every time, Aqueous extracts filtration, merging filtrate obtained medical liquid B.
(3) medical fluid A merges with medical liquid B, is concentrated into relative density 1.25-1.35 (50 DEG C), and 50 DEG C are dried under reduced pressure, and must extract
Object A.
(4) pseudo-ginseng is taken, coarse powder is ground into, 60% alcohol reflux measured with 8 times extracts 2 times, 2 hours every time, filters
It crosses, recycles ethyl alcohol, be concentrated under reduced pressure, be splined on macroreticular resin, successively pass through water, 30%, 70% ethanol elution, collect 70% second
Alcohol eluen, concentration, is dried under reduced pressure to get arasaponin.
(5) by extract A, arasaponin, borneol, muscone, ginseng stem and leave general saponin powder, it is ground into fine powder, is added
Enter corresponding auxiliary material, be uniformly mixed, is packed into capsule, capsule is made.
Test example pharmacodynamic test
Drug effect contrasts sample:
Pharmaceutical composition refers to by pharmaceutical composition prepared by the embodiment of the present invention 1.According to authorization publication number
CN109260260A specification embodiment 1 prepares sample and obtains contrast sample 1.According to authorization publication number CN 1679787A explanation
Book embodiment 2 prepares sample and obtains contrast sample 2.According to authorization 108853294 A specification embodiment 2 of publication number CN preparation
Sample obtains contrast sample 3.
Instrument reagent:
SMP500-18272-LSIO microplate reader: Manufactured in China Designed in California
USA；LD5-2A type low speed centrifuge: Beijing Medical Centrifugal Machine Factory；JA1103N type electronic balance: Shanghai Min Qiao exact science instrument
Device Co., Ltd；Morris rat water maze instrument, acetylcholine Ach and total cholinesterase TchE kit.
Experimental animal:
Wistar rat, half male and half female, SPF grades, 180-220g is purchased from this experimental animal technology Limited Liability of Changchun hundred million
Company.
Pharmaceutical composition of the present invention and contrast sample 1,2,3 carry out effect experiment comparative study, and methods and results are as follows:
1. influence of the pharmaceutical composition to vascular dementia rats
1.1 model foundation
After rat is bought, observation 1 week without exception, carries out swimming acclimatization training and Morris water maze laboratory, rejects not
Qualified rat simultaneously prepares vascular dementia rats model using the improvement permanent ligating methods of bilateral common carotid arteries (2-VO).
With 10% chloraldurate intraperitoneal injection (lg/kg) anesthesia after rat weight, after anaesthetizing and coming into force, rat neck is shaved
Hair, disinfection；Rat neck median incision is taken, cuts skin, then each layer tissue of blunt separation, finds out bilateral common carotid arteries, dual
Silk thread ligation, avoids damage to cervical sympathetic nerve and vagus nerve.Control group gives same operation, but only separates arteria carotis communis not
It is ligatured.4h carries out the evaluation of neurological functional deficit referring to zealonga method after waiting rat anesthesias to revive after modeling experiment
Grade scale is as follows: 0 grade, zero defect；1 grade, not tensible opposite side forelimb；2 grades, opposite side forelimb buckling；3 grades, slightly to opposite side
It turn-takes；4 grades, serious original place is turn-taked；5 grades, opposite side paralysis, in addition it is dead.The selected standard of modeling success animal (according to
It is 2,3 points of animal that 5 grades of point systems of ZeaLonga, which take scoring), filter out successfully animal model 60.
1.2 groupings and administration
Rat 120, blank group 10, sham-operation, remaining rat modeling, takes into random point 8 groups of reviver 80: model
The high, medium and low dosage group 1.2 of group, contrast sample 1, contrast sample 2, contrast sample 3, pharmaceutical composition, 0.6,0.3g/ (kg
D), piracetam group 1g/ (kgd), postoperative 7 days, the equal gastric infusion of each group rat, 1 time a day, and 10ml/kg, continuous gavage administration
45 days, model group gave the same dose of distilled water, and blank group is not processed.
1.3 Testing index
1.3.1 Behaviors survey uses Morris determined with Morris water: water maze is for a circular stainless steel pond, diameter
150cm, high 50cm, depth of water 30cm, water temperature are controlled (25 scholar 1) DEG C, pond are divided into 4 quadrants, each quadrant indicates one
A platform, high 28cm, diameter 15cm are placed in place of entry, an optional quadrant, center, and labyrinth top is equipped with stylus, and
Video recorder is connected with display, and automatic input rats'swimming track is analyzed.
1.3.1.1 orientation navigation experiment: needing 5 days, the every morning same time altogether, by rat from the place of entry of two quadrants
Into the water, it records it and finds time (escape latency) used in platform and swimming path in 2 minutes.If rat is 2
Platform is not found in minute, then incubation period is 120s.And rat is placed in platform 15s, then rat is put back in cage.This experiment
It is swum by trained rat and finds platform.Observe the learning ability of its escape latency and path detection rat of swimming.
1.3.1.2 space exploration is tested: rat removed platform at the 6th day after finishing orientation navigation experiment, selected one
Into the water, each group rat is analyzed in original platform quadrant in swimming track and time of the rat in pond in record 2 minutes to place of entry
The ratio of the time of swimming and path and total swimming time and path.Space learning of this Germicidal efficacy rat after training in 5 days
With the variation of memory, learning and memory normal rat can often remember the spatial position of platform, therefore can find position of platform quickly, remove
After platform, the normal rat of learning and memory can find repeatedly platform in original platform quadrant in 2 minutes, and learning and memory difference
Rat then still purposelessly finds platform in labyrinth.By calculating their ratio, it can further reflect rat
Spatial memory ability.
1.3.2 index determining
1.3.2.1 rat cerebral tissue's Hippocampal Acetylcholine esterase (ACHE), SOD activity and the detection of MDA level
After water maze laboratory, random 5 rats of every group of selection, with taking brain after 10% chloraldurate intraperitoneal injection of anesthesia
Tissue separates hippocampus, is homogenized after cracking, and 12000 revs/min are centrifuged 10 minutes, leave and take supernatant, big using ELISA method detection
Murine brain hippocampus MDA level and SOD Activity determination.
1.3.2.2 serum detects IL-6 and TNF-α
After water maze laboratory, 5 rats of random every group of selection, with abdominal cavity after 10% chloraldurate intraperitoneal injection of anesthesia
Blood is taken, 3000 revs/min are centrifuged 15 minutes, take serum, detect IL-6 and TNF-α using enzyme linked immunosorbent assay.
1.4 experimental result
1.4.1 5 days escape latency results before rat
Compared with blank control group, the incubation period that model group finds platform is obviously prolonged (P < 0.001).With model group ratio
Compared with the incubation period that piracetam group finds platform is obviously shortened (P < 0.05, P < 0.01) in training in two to five days.Comparative sample 1
Incubation period of the group in third day and the 5th day searching platform is obviously shortened (P < 0.05), 2 groups of comparative sample third and fourth, seek within five days
The incubation period of platform is looked for be obviously shortened (P < 0.05), 3 groups of the comparative sample incubation periods in second, five day searching platform are obvious
Shorten (P < 0.05).Pharmaceutical composition low dose group is at second and third, in training in four, five days, shorter latencies (P < 0.05),
The middle and high dosage group of pharmaceutical composition in first, second, third and fourth, five day shorter latencies (P < 0.05, P < 0.01, P < 0.001),
And have statistical difference (P < 0.05) compared with 1,2,3 group of comparative sample, there is obvious effect advantage.It the results are shown in Table 1.
Escape latency result observation in 5 days before 1 each group rat of table
Note: compared with model group#P < 0.05,##P < 0.01,###P<0.001；P < 0.01 * * compared with 1 group of comparative sample；With it is right
Compare P < 0.05 ▽ than 2 groups of sample；Compared with 3 groups of comparative sample□P<0.05。
1.4.2 rat is in original platform quadrant swim time and path and total swimming time and path ratio after removing platform
Compared with blank group, model control group rat primary image limit residence time ratio and distance than there were significant differences (P <
0.001)；Compared with model group, piracetam group, pharmaceutical composition be high, middle dose group primary image limit residence time ratio and distance than
Have significant difference (P < 0.05, P < 0.01), pharmaceutical composition low dose group limits shorter residence time (P < 0.05) in primary image；
Pharmaceutical composition is high, middle dose group has statistical difference (P < 0.05) compared with 1,2,3 group of comparative sample, there is obvious effect advantage.
It the results are shown in Table 2.
Rat is in original platform quadrant swim time and path and total swimming time and path ratio after table 2 removes platform
Note: compared with model group##P < 0.01,###P < 0.001；P < 0.05 * compared with 1 group of comparative sample；With comparative sample 2
Group compares P < 0.05 ▽；P < 0.05 compared with 3 groups of comparative sample.
1.4.3 acetylcholinesterase (ACHE), SOD activity and MDA level content assay result in rat cerebral tissue
Compared with blank group, the horizontal apparent increase of model control group acetylcholinesterase content, MDA (P < 0.01, P <
0.001), SOD vigor obviously lowers (P < 0.001)；Compared with model group, each group can be improved SOD vigor (P < 0.05, P <
0.01,P<0.001)；Compared with 1,2,3 group of comparative sample, acetylcholine esterase contains for pharmaceutical composition high dose group, middle dose group
Amount, MDA content are substantially reduced, and there are significant difference (P < 0.05, P < 0.01, P < 0.001).Such as table 3.
Acetylcholinesterase content, SOD activity and the measurement of MDA level in 3 rat cerebral tissue of table
Note: compared with blank control group###P<0.001；* P < 0.05 compared with model control group, * * P < 0.01, * * * P <
0.001；Compared with 3 groups of comparative sample□P<0.05。
1.4.4 to the influence of IL-6, TNF-α content in rat blood serum
Compared with blank control group, model group IL-6, TNF-α content increase (P < 0.001)；Compared with model group, each group
Can obviously reduce IL-6, TNF-α content (P < 0.05, P < 0.01, P < 0.001), pharmaceutical composition be high, middle dose group with
1,2,3 group of comparative sample is compared, and IL-6, TNF-α are substantially reduced (P < 0.05), there is obvious effect advantage.It the results are shown in Table 4.
4 rat blood serum IL-6 of table, TNF-α assay
Note: compared with model group##P < 0.01,###P < 0.001；P < 0.05 * compared with 1 group of comparative sample；With comparative sample 2
Group compares P < 0.05 ▽；P < 0.05 compared with 3 groups of comparative sample.
1.5 conclusion
This research pharmaceutical composition can be obviously improved vascular dementia rats spatial cognition memory capability and exploratory behavior,
Its mechanism for playing neuroprotection may, antioxidant stress injury anti-inflammatory to its effect it is clear related.And the and prior art
The comparative sample of preparation relatively also shows that apparent advantage function.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of Chinese medicine composition treats or prevents the application in vascular senile dementia drug in preparation, which is characterized in that institute
Chinese medicine composition is stated by Radix Salviae Miltiorrhizae, Radix Notoginseng, safflower, Herba Epimedii, Pachyrhizua angulatus, Radix Curcumae, peach kernel, Rhizoma Chuanxiong, leech, borneol, Moschus, ginseng stem
Leaf total saposins are made.
2. application according to claim 1, which is characterized in that in parts by weight, the Chinese medicine composition by Radix Salviae Miltiorrhizae 10~
12 parts, 0.5~1 part of Radix Notoginseng, 2~4 parts of safflower, 4~6 parts of Herba Epimedii, 4~6 parts of Pachyrhizua angulatus, 2~4 parts of Radix Curcumae, 9~12 parts of peach kernel,
1~3 part of Rhizoma Chuanxiong, 1~3 part of leech, 0.1~0.3 part of borneol, 0.005~0.01 part of Moschus, ginseng stem and leave general saponin 0.05~
0.1 part is made.
3. application according to claim 1, which is characterized in that in parts by weight, the Chinese medicine composition by 10 parts of Radix Salviae Miltiorrhizae,
0.5 part of Radix Notoginseng, 2.5 parts of safflower, 4 parts of Herba Epimedii, 4 parts of Pachyrhizua angulatus, 2.5 parts of Radix Curcumae, 9.8 parts of peach kernel, 1 part of Rhizoma Chuanxiong, 1.3 parts of leech,
0.1 part of borneol, 0.008 part of Moschus, 0.08 part of ginseng stem and leave general saponin be made.
4. application according to any one of claim 1 to 3, which is characterized in that the preparation method of the Chinese medicine composition
Include the following steps:
(1) leech is crushed, adds the water of 8~12 times of weight, be homogenized, impregnated, filtration；Take filter residue, then plus 3~5 times of weight water,
Homogenate is impregnated, filtration；Merging filtrate, centrifugation, takes supernatant, obtains medical fluid A；
(2) Radix Salviae Miltiorrhizae, safflower, peach kernel, Pachyrhizua angulatus, Rhizoma Chuanxiong, Radix Curcumae, Herba Epimedii are taken, is crushed, the water of 6~10 times of weight is added, is impregnated,
Refluxing extraction, Aqueous extracts filtration, obtains medical liquid B；
(3) medical fluid A merges with medical liquid B, and concentration is dried under reduced pressure, obtains extract A；
(4) Radix Notoginseng being crushed, the ethanol water refluxing extraction of 8~10 times of weight is added, ethyl alcohol is recycled in filtration, it is concentrated under reduced pressure,
It is splined on macroreticular resin, successively passes through water, 30% ethyl alcohol, 70% ethanol elution, collects 70% ethanol eluate, is concentrated, decompression
It is dry, obtain arasaponin；
(5) extract A, arasaponin, borneol, Moschus, ginseng stem and leave general saponin are crushed, is uniformly mixed.
5. application according to claim 4, which is characterized in that in step (1), the temperature of immersion is 0~8 DEG C, immersion
Time is 10~14 hours；The time of homogenate is 30~60 minutes；The revolving speed of centrifugation be 3000~5000r/min, centrifugation when
Between be 5~10 minutes.
6. application according to claim 4, which is characterized in that in step (2), the time of immersion is 0.5~2 hour, often
The time of secondary refluxing extraction is 1~3 hour, and the number of refluxing extraction is 2~3 times, Aqueous extracts filtration, merging filtrate.
7. application according to claim 4, which is characterized in that in step (3), the relative density 1.25 that is concentrated at 50 DEG C
~1.35, the temperature being dried under reduced pressure is 40~60 DEG C.
8. application according to claim 4, which is characterized in that in step (4), the volumn concentration of ethanol water is
70%~80%；The number of refluxing extraction is 2~3 times, every time 1~3 hour.
9. application according to claim 1, which is characterized in that the treatment or prevention vascular senile dementia drug also wraps
Include pharmaceutically acceptable auxiliary material.
10. application according to any one of claim 1 to 9, which is characterized in that the treatment or prevention vascular senile
The dosage form of anti-dementia agent is granule, tablet, capsule or pill.
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