CN104958572B - Traditional Chinese medicine composition for treating ischemia apoplexy and post-stroke depression and preparation method of traditional Chinese medicine composition - Google Patents
Traditional Chinese medicine composition for treating ischemia apoplexy and post-stroke depression and preparation method of traditional Chinese medicine composition Download PDFInfo
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Abstract
The invention relates to a traditional Chinese medicine composition for treating ischemia apoplexy and post-stroke depression and a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following main raw materials in parts by weight: 10-100 parts of ginseng, 10-500 parts of ginkgo leaves, 10-150 parts of radix scutellariae, 10-200 parts of fructus gardenia, 10-200 parts of rhizoma gastrodiae, 10-200 parts of ligusticum wallichii and 10-200 parts of hyperforin perforatum. The traditional Chinese medicine composition is obvious in treatment effects on ischemia apoplexy and post-stroke depression. The pharmacodynamic test proves that the traditional Chinese medicine composition is excellent in treatment effects on ischemia apoplexy and post-stroke depression.
Description
Technical field
The invention belongs to field of Chinese herbal, more particularly to a kind of Chinese medicine composition for treating cerebral infarction and type post-stroke depression
Thing and its preparation method.
Background technology
At present China's Apoplexy Morbidity is higher, and cerebral infarction accounts for apoplexy 60-80%, its high disability rate, high fatality rate
And its sequela --- type post-stroke depression brings dual-pressure to health care and social economy.Western medicine is in stroke in convalescent stage
Lack effective therapy in treatment, big drug has limitation, and late result is not good enough, there are problems in treatment, thus
Wide clinical application is subject to larger restriction.Treatment by Chinese herbs cerebral infarction convalescent period relevant disease clinical efficacy is definite, and poison is secondary to be made
With relatively small, clinical practice extensively, while it is relatively large to there is also dosage, the features such as work slower, but from treatment at a specified future date
From the point of view of effect, advantage of the Chinese medicine in clinical treatment is far longer than shortcoming.From in terms of research and application trend, treatment by Chinese herbs ischemic brain
Relevant vascular diseases, in the recent period or late result and popularization and application it is all more promising.Therefore, development quality is stable, curative effect is true
Dig, have very much realistic meaning using convenient new Chinese medicine.
The content of the invention
It is an object of the invention to provide a kind of Chinese medicine composition for treating cerebral infarction and type post-stroke depression.
Another object of the present invention is to provide above-mentioned Chinese medicine composition press down after treatment cerebral infarction and apoplexy is prepared
Purposes in strongly fragrant medicine.
The present invention is achieved through the following technical solutions：
A kind of Chinese medicine composition for treating cerebral infarction and type post-stroke depression, the primary raw material weight of the Chinese medicine composition
Amount part consists of：
Radix Ginseng 10-100 Folium Ginkgo 10-500 Radix Scutellariae 10-150
Fructus Gardeniae 10-200 Rhizoma Gastrodiae 10-200 Rhizoma Chuanxiong 10-200
Herba Hyperici perforati 10-200.
Preferably, the Chinese medicine composition also includes the raw material of following weight portion composition：
Radix Salviae Miltiorrhizae 10-200.
Preferably, the Chinese medicine composition also includes the raw material of following weight portion composition：
Radix Rhodiolae 10-200.
Preferably, the Chinese medicine composition also includes the raw material of following weight portion composition：
Radix Salviae Miltiorrhizae 10-200 Radix Rhodiolae 10-200.
Preferably, the primary raw material weight portion of the Chinese medicine composition is consisted of：
Preferably, the Chinese medicine composition includes the raw material of following weight portion composition：
Preferably, the Chinese medicine composition includes the raw material of following weight portion composition：
Preferably, the Chinese medicine composition includes the raw material of following weight portion composition：
The preparation method of above-mentioned Chinese medicine composition, comprises the following steps：
Whole crude drug are added water to cook after extraction gained extracting solution concentration plus ethanol precipitate with ethanol after crushing, and reclaim ethanol, concentration
To thick paste, the Chinese medicine composition is obtained final product.
Preferably, comprise the following steps：
Whole crude drug add water to cook extraction 2-4 time after crushing, each amount of water is 5-20 times of crude drug gross weight and measures, often
Secondary decocting time is 1-3h, merges decocting liquid, is concentrated into relative density 1.05-1.25, plus 95% ethanol precipitate with ethanol, places 12-24
Hour, supernatant is taken, decompression recycling ethanol is concentrated into thick paste, obtains final product the Chinese medicine composition to without alcohol taste.
A kind of preferred embodiment, after the thick paste drying, crushing, adds or is added without adjuvant, makes solid preparation,
Such as tablet, capsule, pill, granule etc., more preferably capsule.
Preferred another embodiment, the thick paste can add adjuvant after solubilizer dissolving, make liquid preparation, example
Such as oral liquid formulations.
Additionally, the Chinese medicine composition of the present invention can also be prepared with alcohol extracting method.
The present invention also provides the preparation for treating cerebral infarction and type post-stroke depression, includes above-mentioned in the preparation
Chinese medicine composition.
The present invention also provides above-mentioned Chinese medicine composition in the medicine for the treatment of cerebral infarction and type post-stroke depression is prepared
Purposes.
The cerebral infarction that Chinese medicine composition of the present invention is cured mainly mainly blame in qi depression to blood stasis, stagnation of blood stasis and heat, resistance network stop up key,
Blood stasis, the heresy of pyretic toxicity are its main pathological basis, are carried throughout.For preparing the Chinese medicine composition of the present invention, prescription rationally, is pressed
Solve according to the side of traditional medicine, Radix Ginseng is monarch drug, sweet and slightly bitter taste, returns spleen, lung meridian, heart channel；Can invigorating QI to relieve exhaustion, tranquilize the mind and promote the intelligence, this
The effect of QI invigorating is primarily served in side.Folium Ginkgo, Radix Scutellariae, Fructus Gardeniae are ministerial drug, and Folium Ginkgo bitter in the mouth is mild-natured, promoting blood circulation and stopping pain；Radix Scutellariae taste
Bitterness is trembled with fear, can heat clearing and damp drying, eliminating fire and detoxication；Fructus Gardeniae bitter cold, clearing away heat-fire, removing pathogenic heat from blood and toxic substance from the body；Three taste ministerial drugs coordinate can activating blood circulation,
Clearing heat and relieving fidgetness, pathogenic fire purging of detoxifying.Rhizoma Gastrodiae, Rhizoma Chuanxiong, Herba Hyperici perforati are adjuvant drug, and Rhizoma Gastrodiae sweet in the mouth is mild-natured, dispelling wind and relieving convulsion, resolving sputum；Rhizoma Chuanxiong taste
It is pungent warm in nature, blood circulation promoting and blood stasis dispelling, wind-expelling pain-stopping；Herba Hyperici perforati, acrid in the mouth slight bitter, heat-clearing and toxic substances removing, convergence；Three taste adjuvant drugs coordinate can dredging collateral put out
Wind, Huoxue Jieyu, and the up mountain peak top of priming, demonstrate,prove for the strongly fragrant poison resistance network of stroke in convalescent stage blood stasis due to qi deficiency wind-phlegm, symptoms include hemiplegia,
Crooked mouth and tongue, dysphasia, depressed emotion, numb limbs and tense tendons.Radix Salviae Miltiorrhizae is bitter, is slightly cold, GUIXIN, Liver Channel；Blood circulation promoting and blood stasis dispelling, inducing menstruation to relieve menalgia,
Relieving restlessness that clears away heart-fire, cool blood to disappear carbuncle；Obstruction of qi in the chest and cardialgia is cured mainly, gastral cavity abdomen hypochondriac pain, abdominal mass abdominal mass is gathered, hot numbness pain, dysphoria and insomnia, menoxenia,
Dysmenorrhea amenorrhea, sore swell and ache curative.Radix Rhodiolae is cold, sweet, puckery.Return lung Jing；There are tonifying Qi clearing lung-heat, Fructus Alpiniae Oxyphyllae nourishing heart, hemostasis with astringents, dissipating blood stasis for subsidence of swelling
Effect.Cure mainly deficiency of vital energy and physically weak, after being ill fear of cold, shortness of breath and fatigue, cough due to lung-heat, spitting of blood, leucorrhea diarrhoea, traumatic injury etc..Radix Salviae Miltiorrhizae
With Radix Rhodiolae ministerial drug can be coordinated to play a part of disperse blood stasis and dredge collateral removing heat from blood with adjuvant drug.In long-term clinical practice of Chinese medicine, the present invention
Treatment of the Chinese medicine composition to cerebral infarction and type post-stroke depression, achieve significant clinical effectiveness, curative effect determines, safety
Effectively.In practical application, according to the difference of patient's condition, under the premise of the composition principle without departing from the Chinese medicine composition, institute
Stating the consumption of each taste crude drug in Chinese medicine composition can be adjusted in the scope.The present invention research show, the medical instrument
There are the action characters different from the similar Chinese medicine (such as BUCHANG NAOXINTONG) of current Clinical practice, which show more advantageous treatment
Effect, analyzes its mechanism, with the amount of blood supply and microcirculation for increasing ischemic brain area, suppresses the abnormal release of excitatory amino acid and mitigates
The inflammatory reaction of central nervous system is relevant.
The beneficial effects of the present invention is：
The Chinese medicine composition of the present invention, is Chinese medicine compound, pays attention to the enhancing of autoimmune system, is had no toxic side effect, group
Fang Heli；
Effectively for apoplexy and the main pathogenesis of type post-stroke depression, for example, reduce cerebral ischemia area, mitigate nerve
Dysfunction, improves body weight and activeness after depression, reduces desperate degree etc., evident in efficacy；
Simultaneously dosage is also farthest reduced, improve drug effect, actually reach high-efficiency low-toxicity；
Crude drug wide material sources, it is easy to obtain, are easy to prepare and large-scale production.
Specific embodiment
Chinese medicine composition and the preparation method of Chinese medicine composition below in the way of specific embodiment to the present invention is carried out in detail
Illustrate, but embodiment does not have restriction effect to protection scope of the present invention, and those skilled in the art can be according to these enforcements
The exemplary effect of example, understands the composition and preparation method of Chinese medicine composition of the present invention.
The Chinese medicine composition of embodiment 1
Prescription：
Radix Ginseng 60g, Folium Ginkgo 120g, Radix Scutellariae 60g, Fructus Gardeniae 60g, Rhizoma Gastrodiae 60g, Rhizoma Chuanxiong 60g, Herba Hyperici perforati 60g.
Preparation method：
Whole crude drug add water to cook extraction 4 times after crushing, each amount of water is 20 times of amounts of crude drug gross weight, decocts every time
The time is boiled for 3h, merges decocting liquid, be concentrated into relative density 1.05, plus 95% ethanol precipitate with ethanol, stood overnight, take supernatant, subtracted
Receipts ethanol is pushed back to without alcohol taste, thick paste is concentrated into, the Chinese medicine composition is obtained final product.
The Chinese medicine composition of embodiment 2
Prescription：
Radix Ginseng 6g, Folium Ginkgo 12g, Radix Scutellariae 6g, Fructus Gardeniae 6g, Rhizoma Gastrodiae 6g, Rhizoma Chuanxiong 6g, Herba Hyperici perforati 6g, Radix Salviae Miltiorrhizae 6g, Radix Rhodiolae
6g。
Preparation method：
Whole crude drug add water to cook extraction 3 times after crushing, each amount of water is 15 times of amounts of crude drug gross weight, decocts every time
The time is boiled for 2h, merges decocting liquid, be concentrated into relative density 1.10, plus 95% ethanol precipitate with ethanol, stood overnight, take supernatant, subtracted
Receipts ethanol is pushed back to without alcohol taste, thick paste is concentrated into, the Chinese medicine composition is obtained final product.
The Chinese medicine composition of embodiment 3
Prescription：
Radix Ginseng 1000g, Folium Ginkgo 2000g, Radix Scutellariae 1000g, Fructus Gardeniae 1000g, Rhizoma Gastrodiae 1000g, Rhizoma Chuanxiong 1000g, pass through leaf company
Stick up 1000g, Radix Salviae Miltiorrhizae 1000g.
Preparation method：
Whole crude drug add water to cook extraction 2 times after crushing, each amount of water is 10 times of amounts of crude drug gross weight, decocts every time
The time is boiled for 1.5h, merges decocting liquid, be concentrated into relative density 1.15, plus 95% ethanol precipitate with ethanol, stood overnight, take supernatant,
Decompression recycling ethanol is concentrated into thick paste to without alcohol taste, obtains final product the Chinese medicine composition.
The Chinese medicine composition of embodiment 4
Prescription：
Radix Ginseng 50g, Folium Ginkgo 120g, Radix Scutellariae 50g, Fructus Gardeniae 50g, Rhizoma Gastrodiae 50g, Rhizoma Chuanxiong 50g, Herba Hyperici perforati 50g, Radix Rhodiolae
100g。
Preparation method：
Whole crude drug add water to cook extraction 2 times after crushing, each amount of water is 5 times of amounts of crude drug gross weight, decocts every time
The time is boiled for 1h, merges decocting liquid, be concentrated into relative density 1.25, plus 95% ethanol precipitate with ethanol, stood overnight, take supernatant, subtracted
Receipts ethanol is pushed back to without alcohol taste, thick paste is concentrated into, the Chinese medicine composition is obtained final product.
The Chinese medicine composition of embodiment 5
Prescription：
Radix Ginseng 200g, Folium Ginkgo 500g, Radix Scutellariae 200g, Fructus Gardeniae 200g, Rhizoma Gastrodiae 200g, Rhizoma Chuanxiong 200g, Herba Hyperici perforati 200g.
Preparation method：
Whole crude drug add water to cook extraction 3 times after crushing, each amount of water is 10 times of amounts of crude drug gross weight, decocts every time
The time is boiled for 2h, merges decocting liquid, be concentrated into relative density 1.15, plus 95% ethanol precipitate with ethanol, stood overnight, take supernatant, subtracted
Receipts ethanol is pushed back to without alcohol taste, thick paste is concentrated into, the Chinese medicine composition is obtained final product.
The Chinese medicine composition of embodiment 6
Prescription：
Radix Ginseng 100g, Folium Ginkgo 500g, Radix Scutellariae 150g, Fructus Gardeniae 200g, Rhizoma Gastrodiae 200g, Rhizoma Chuanxiong 200g, Herba Hyperici perforati 200g.
Preparation method：
Whole crude drug add water to cook extraction 3 times after crushing, each amount of water is 20 times of amounts of crude drug gross weight, decocts every time
The time is boiled for 3h, merges decocting liquid, be concentrated into relative density 1.15, plus 95% ethanol precipitate with ethanol, stood overnight, take supernatant, subtracted
Receipts ethanol is pushed back to without alcohol taste, thick paste is concentrated into, the Chinese medicine composition is obtained final product.
The Chinese medicine composition of embodiment 7
Prescription：
Radix Ginseng 50g, Folium Ginkgo 250g, Radix Scutellariae 100g, Fructus Gardeniae 50g, Rhizoma Gastrodiae 50g, Rhizoma Chuanxiong 100g, Herba Hyperici perforati 100g.
Preparation method：
Whole crude drug add water to cook extraction 1 time after crushing, each amount of water is 15 times of amounts of crude drug gross weight, decocts every time
The time is boiled for 1h, merges decocting liquid, be concentrated into relative density 1.05, plus 95% ethanol precipitate with ethanol, stood overnight, take supernatant, subtracted
Receipts ethanol is pushed back to without alcohol taste, thick paste is concentrated into, the Chinese medicine composition is obtained final product.
The Chinese medicine composition of embodiment 8
Prescription：
Radix Ginseng 10g, Folium Ginkgo 20g, Radix Scutellariae 10g, Fructus Gardeniae 10g, Rhizoma Gastrodiae 10g, Rhizoma Chuanxiong 10g, Herba Hyperici perforati 10g, Radix Salviae Miltiorrhizae
10g, Radix Rhodiolae 10g.
Preparation method：
Whole crude drug add water to cook extraction 2 times after crushing, each amount of water is 5 times of amounts of crude drug gross weight, decocts every time
The time is boiled for 3h, merges decocting liquid, be concentrated into relative density 1.05, plus 95% ethanol precipitate with ethanol, stood overnight, take supernatant, subtracted
Receipts ethanol is pushed back to without alcohol taste, thick paste is concentrated into, the Chinese medicine composition is obtained final product.
The capsule of embodiment 9
It is spray-dried to obtain dry extract from the gained Chinese medicine composition thick paste of embodiment 3,400g dry extracts are taken,
By Chinese medicine composition dry extract and adjuvant 1：1 mass ratio is mixed, and adjuvant includes that mass ratio is 1:2 solubility is formed sediment
Powder and Microcrystalline Cellulose.Thin slice is pressed into dry crowded granulator, then is ground into granule.Fine particle is filled in 0# Capsuleses and makes
It is standby to obtain capsule.
The capsule of embodiment 10
It is spray-dried to obtain dry extract from the gained Chinese medicine composition thick paste of embodiment 1,300g dry extracts are taken,
By Chinese medicine composition dry extract and adjuvant 1：2.5 mass ratio is mixed, and adjuvant includes that mass ratio is 1:1:1 it is solvable
Property starch, Microcrystalline Cellulose and Mannitol.Thin slice is pressed into dry crowded granulator, then is ground into granule.Fine particle is filled in 0#
Capsule is prepared in Capsuleses.
The granule of embodiment 11
It is spray-dried to obtain dry extract from the gained Chinese medicine composition thick paste of embodiment 6,300g dry extracts are taken,
By Chinese medicine composition dry extract and adjuvant 1：1 mass ratio is mixed, and adjuvant includes that mass ratio is 1:1:1 Fructus Hordei Germinatus paste
Essence and Microcrystalline Cellulose and Lactose.Thin slice is pressed into dry crowded granulator, then is ground into granule.Granule Jing granulate, pelletize again, powder
Mix suspension grain agent is prepared into after broken.
The granule of embodiment 12
It is spray-dried to obtain dry extract from the gained Chinese medicine composition thick paste of embodiment 7,150g dry extracts are taken,
By Chinese medicine composition dry extract and adjuvant 1：2 mass ratio is mixed, and adjuvant includes that mass ratio is 1:1:1 solubility
Starch, maltodextrin and Mannitol.Thin slice is pressed into dry crowded granulator, then is ground into granule.Granule Jing granulate, pelletize again, powder
Mix suspension grain agent is prepared into after broken.
Pharmacodynamics test
Chinese medicine composition of the present invention is clinical experience side, summarizes multi-party experience, and many years clinical practice empiricals of Jing are cut out and formed,
To cerebral infarction and type post-stroke depression effect is significant.By pharmacodynamics test, it was demonstrated that by the Chinese medicine composition of the present invention to lacking
Courageous and upright apoplexy and type post-stroke depression have good therapeutical effect.
Test example 1：The therapeutical effect of focal cerebral ischemia in rats rat prepared by line brush
Test material
1. test medicine
Using the Chinese medicine composition of the embodiment of the present invention 1
2. test medicine
Ginaton, 40mg/ pieces, Dr Willmar Schwabe's production, lot number：4181212.
3. animal
SD rats, male, 64,220-240g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., qualified
Card number：SCXK (capital) 2012-0001.
Test method
1. model is set up
Evaluating focal brain ischemia in rats is prepared with reference to method Jing such as Longa common carotid artery insertion nylon wire bolt.Animal fiber crops
Liquor-saturated, dorsal positions are fixed on insulation blanket, separate CCA, ICA and ECA, are ligatured ECA and are cut off, and CCA silk threads beat slip-knot temporary interruption,
Closed after ICA with bulldog clamp folder, in ECA otch is cut off, insert the nylon wire of a diameter of 0.24mm to having obvious resistance, insertion depth
20 ± 2mm (from common carotid artery crotch meter), causes middle cerebral artery occlusion ischemia, forms evaluating focal brain ischemia in rats.
Sham operated rats only separate CCA ligation ECA, do not insert nylon wire.Extract nylon wire after 1.5h out, decontrol CCA silk threads, realize Reperfu- sion.
37 DEG C to 37.5 DEG C of insulation blanket design temperature in experimentation, keep rat temperature.
2. test is grouped and medication
8 groups of test point, 8 mices are randomly selected per group：
(1) sham operated rats, (normal saline of 2ml/kg body weight)；
(2) model group, (normal saline of 2ml/kg body weight)；
(3) (Ginaton 20mg/kg body weight, by the medicine drug solution is configured to positive drug group, and its dosage presses volume
It is calculated as 2ml/kg body weight)；
(4) 1 group of Chinese medicine composition of the present invention (dosage 0.07g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 2ml/kg body weight)；
(5) 2 groups of Chinese medicine composition of the present invention (dosage 0.15g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 2ml/kg body weight)；
(6) 3 groups of Chinese medicine composition of the present invention (dosage 0.30g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 2ml/kg body weight)；
(7) 4 groups of Chinese medicine composition of the present invention (dosage 0.60g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 2ml/kg body weight)；
(8) 5 groups of Chinese medicine composition of the present invention (dosage 1.20g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 2ml/kg body weight).
Medication：At once by the medicine and dosage of each group, Jing duodenal administrations after cerebral ischemia.
3. Index for examination and standard
3.1 neuroethology
Using mono blind method observation neuroethology (5 points of standards of grading processed of longa), standard is 4,24h after ischemia：
0 point：Impassivity injury symptoms；
1 point：It is unable to full extension left side fore paw；
2 points：Turn-take to non-ischemia side；
3 points：Roll to non-ischemia during walking；
4 points：Spontaneous can not walk, consciousness stupor.
3.2 Brain stem injury
Animal broken end takes blood after last scoring, takes out brain, weighs, and is averagely cut into 5 brain pieces, TTC dyeing, customized multimedia
Color pathology picture and text analysis system counts rat whole brain area and brain infarction area, and with infarct size/full brain cartographic represenation of area cerebral infarction
Dead scope.Statistical data analysis are represented with mean ± SD.Brain stem injury is with t check analyses group differences；Neurobehavioral obstacle
Counted with rank value test.
4. result of the test
The impact of 4.1 pairs of function of nervous system
After administration 4h, compare with model group, 4 groups of Chinese medicine composition of the present invention (0.60g/kg body weight), 5 groups of (1.20g/kg
Body weight) neural behavior scoring substantially reduces (P<0.05).After administration 24h, compare with model group, positive drug (Ginaton) can be obvious
Reduce neural behavior scoring (P<0.05)；3 groups of Chinese medicine composition of the present invention (0.30g/kg body weight), 4 groups (0.60g/kg body weight),
5 groups of (1.20g/kg body weight) neural behavior scorings substantially reduce (P<0.05).The results are shown in Table 1.
Impact of the table 1 to cerebral ischemia re-pouring model neural behavior scoring
Note：Compare with model group：*P<0.05, * * P<0.01
The impact of 4.2 pairs of Brain stem injuries
After modeling 24h, compare with model group, positive drug can be obviously reduced Brain stem injury (P<0.05), medicine of the present invention
2 groups of Chinese medicine composition of the present invention (0.15g/kg body weight), 3 groups (0.3g/kg body weight), 4 groups (0.60g/kg body weight), 5 groups
(1.20g/kg body weight), is significantly reduced Brain stem injury (P<0.05, P<0.01).The results are shown in Table 2.
Impact of the table 2 to cerebral ischemia re-pouring model Brain stem injury
Note：Compare with model group：*P<0.05, * * P<0.01
5. conclusion
The Chinese medicine composition of the present invention can treat focal cerebral ischemia, and 0.15g Chinese medicine compositions/kg body weight for the present invention
The effective dose of Drug therapy cerebral ischemia.
Test example 2：The therapeutical effect of permanent cerebral ischemia rat model prepared by line brush
Test material
1. test medicine
Using the Chinese medicine composition of the embodiment of the present invention 1.
2. test medicine
Ginaton, 40mg/ pieces, Dr Willmar Schwabe's production, lot number：4181212.
3. animal
SD rats, male, 60,220-240g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., qualified
Card number：SCXK (capital) 2012-0001.
Test method
1. model is set up
Rat permanent cerebral ischemia model is prepared with reference to the method Jing common carotid artery such as Longa insertion nylon wire bolt.With reference to office
Stove cerebral ischemia re-pouring experimental technique, sets up permanent cerebral ischemia model.Jing common carotid artery insertion nylon wire bolt prepares rat
Focal cerebral ischemia in rats.Animal Anesthesia, dorsal positions are fixed on insulation blanket, separate CCA, ICA and ECA, are ligatured ECA and are cut off,
CCA silk threads beat slip-knot temporary interruption, are closed after ICA with bulldog clamp folder, and in ECA otch is cut off, and insert the Buddhist nun of a diameter of 0.24mm
To there is obvious resistance, 20 ± 2mm of insertion depth (from common carotid artery crotch meter) causes middle cerebral artery occlusion ischemia to imperial line,
Form rat cerebral ischemia model.Sham operated rats only separate CCA ligation ECA, do not insert nylon wire.Insulation blanket setting temperature in experimentation
37 DEG C to 37.5 DEG C of degree, keeps rat temperature.
2. test is grouped and medication
6 groups of test point：
(1) sham operated rats (normal saline of 2ml/kg)；
(2) model group (normal saline of 2ml/kg)；
(3) (Ginaton 20mg/kg body weight, by the medicine drug solution is configured to positive drug group, and its dosage presses volume
It is calculated as 2ml/kg body weight)；
(4) 1 group of Chinese medicine composition of the present invention (dosage 0.15g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 2ml/kg body weight)；
(5) 2 groups of Chinese medicine composition of the present invention (dosage 0.30g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 2ml/kg body weight)；
(6) 3 groups of Chinese medicine composition of the present invention (dosage 0.60g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 2ml/kg body weight).
Medication：At once by the medicine and dosage of each group, Jing duodenal administrations after cerebral ischemia.
3. Index for examination and standard
3.1 neuroethology
Using mono blind method observation neuroethology (5 points of standards of grading processed of longa), standard is 4,24h after ischemia：
0 point：Impassivity injury symptoms；
1 point：It is unable to full extension left side fore paw；
2 points：Turn-take to non-ischemia side；
3 points：Roll to non-ischemia during walking；
4 points：Spontaneous can not walk, consciousness stupor.
3.2 Brain stem injury
Animal broken end takes blood after last scoring, takes out brain, weighs, and is averagely cut into 5 brain pieces, TTC dyeing, customized multimedia
Color pathology picture and text analysis system counts rat whole brain area and brain infarction area, and with infarct size/full brain cartographic represenation of area cerebral infarction
Dead scope.Statistical data analysis are represented with mean ± SD.Brain stem injury is with t check analyses group differences；Neurobehavioral obstacle
Counted with rank value test.
4. result of the test
The impact of 4.1 pairs of function of nervous system
After administration 4h, compare with model group, positive drug (Ginaton) can improve impaired function of nervous system (P<0.05)；This
3 groups of bright Chinese medicine composition (0.60g/kg body weight) neural behavior scoring is also presented reduction trend.After administration 24h, with model group ratio
Compared with positive drug (Ginaton) can obviously reduce neural behavior scoring (P<0.05)；3 groups of (0.60g/ of Chinese medicine composition of the present invention
Kg body weight) neural behavior scoring substantially reduces (P<0.05).The results are shown in Table 3.
Impact of the table 3 to permanent cerebral ischemia model neural behavior scoring
Note：Compare with model group：*P<0.05, * * P<0.01
The impact of 4.2 pairs of Brain stem injuries
After modeling 24h, compare with model group, positive drug can be obviously reduced Brain stem injury (P<0.01), medicine of the present invention
1 group of Chinese medicine composition of the present invention (0.15g/kg body weight), 2 groups (0.3g/kg body weight), 3 groups (0.6g/kg body weight), can significantly subtract
Cerebellar Infarction scope (P<0.05, P<0.01).The results are shown in Table 4.
Impact of the table 4 to permanent cerebral ischemia model Brain stem injury
Note：Compare with model group：*P<0.05, * * P<0.01
5. conclusion
Jing after duodenum gives rat medicine of the present invention, rat neurological deficit score, Brain stem injury obtain different journeys
Degree improves, and points out medicine of the present invention to play the role of to improve nervous symptoms and the cerebral ischemia of above-mentioned model ischemia brain injury, can use
In treatment permanent cerebral ischemia.
Test example 3：Therapeutical effect to type post-stroke depression rat model
Test material
1. test medicine
Using the Chinese medicine composition of the embodiment of the present invention 1.
2. test medicine
4.0% chloral hydrate, 500g/ bottles, Chemical Reagent Co., Ltd., Sinopharm Group, lot number 20131027；
BUCHANG NAOXINTONG JIAONANG, 0.4g/ grains, Shaanxi Buchang Pharmaceuticals Co., Ltd.'s production, lot number：140414；
Distilled water.
3. animal
SD rats, male, 60,230-260g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., qualified
Card number：SCXK (capital) 2012-0001.
Test method
1. model is set up
Animal weighs in, carries out after the Behavior Tests such as spacious field, outstanding tail, non-swimming time, sucrose solution preference, with tremulous pulse
Injectable microsphere method prepares multiple infarctions model, and medium-term and long-term raising causes type post-stroke depression test model.4.0% chloral hydrate
Intraperitoneal injection of anesthesia (400mg/kg body weight), dorsal positions are fixed on insulation blanket, separate right carotid (CCA), internal carotid artery
(ICA) and external carotid artery (ECA), ligation ECA simultaneously cuts off, and CCA silk threads beat slip-knot temporary interruption, is pressed from both sides with bulldog clamp and is closed after ICA,
Otch is cut off in ECA, fluorescent microsphere suspension serum is injected, the multiple obstruction of arteriae cerebri is caused.False art group only separates CCA ligation
ECA, not injectable microsphere.37 DEG C to 37.5 DEG C of insulation blanket design temperature in experimentation, keep rat temperature.
2. test is grouped and medication
After multiple infarctions model is set up, neurological score is carried out within second day to animal, reject 0 point and 4 points of rats, remaining
Random packet.
6 groups of test point：
(1) sham operated rats (10ml/kg distilled water)；
(2) model group (10ml/kg distilled water)；
(3) (BUCHANG NAOXINTONG JIAONANG 800mg/kg body weight, by the medicine drug solution is configured to positive drug group, its medication
Dosage is by volume 10ml/kg body weight)；
(4) 1 group of Chinese medicine composition of the present invention (dosage 0.15g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 10ml/kg body weight)；
(5) 2 groups of Chinese medicine composition of the present invention (dosage 0.30g/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 10ml/kg body weight)；
(6) 3 groups of Chinese medicine composition of the present invention (dosage 0.60/kg body weight, by the medicine drug solution is configured to, its
Dosage is by volume 10ml/kg body weight).
Medication：Gastric infusion, sham-operation and model group give the distilled water of same volume, successive administration 4 weeks.
3. Index for examination and standard
Animal weighs in, Neuroscore is carried out, when measure non-swimming time, outstanding tail are motionless after last dose
Between, rat grip, carry out sucrose solution preference experiment, spacious field experiment.Euthanasia simultaneously takes out rapidly brain, coronal away from trailing edge 4mm to cut
One knife, liquid nitrogen solidification forebrain, -80 DEG C of preservations, HPLC combined with electrochemical detector determines monoamine neurotransmitters.
Sucrose solution preference is tested：Basic sucrose solution/pure water consumption experiment is carried out to rat, by the equal single cage observation of all rats, should
Elder generation's animal training adapts to drinking-water containing sugar before swashing, and 2 bottles are given simultaneously per cage, and in 2 bottles 1% sucrose water is respectively arranged with, and prohibits after 24h
After water 6h, while every rat measured 2 bottles of water in advance is given, 1 bottled 1% sucrose water, 1 bottled sterilization ordinary water, after 1h,
Take 2 bottles away and weigh.1 sucrose solution experiment, 23h fasting for solids and liquids before experiment, remaining operation stress again be carried out by 21 days every rats afterwards
Ditto.Calculate stress before and after animal liquid wastage in bulk or weight, sucrose solution consumption, pure water consumption, sucrose solution preference percentage ratio (sucrose solution preference hundred
Point than=sucrose solution consumption/always liquid-consumed × 100%).
The measure of non-swimming time：Rat is placed in the glass jar of depth of water 30cm, 25 ± 2 DEG C of water temperature, rat is kept
Hind leg can not touch cylinder bottom, and forelimb can not invest casing wall top.Observation 5min, the accumulation dead time after record in 3min.
Spacious field is tested：For cube, a height of 40cm, length and width are respectively 80cm to the spacious case for adopting, and perisporium is black, and bottom surface is by face
The equal 25 squares composition of product.With animal travels ground block number as horizontal movement score (crossing), the lattice (3 of animal travels 1
More than pawl stride into) for 1 point, such as animal walks along the line, with every 10cm as 1 point；With upright number of times as the score that moves vertically
(rearing), animal biped leaves bottom surface to indicate, no matter how long animal stands until putting down biped for 1 point.Per only moving
Thing is carried out 1 time, and each time is 3min.
The measure of outstanding tail dead time：Using the outstanding foot piece of self-control, rat tailses are at tail point 3cm with soft folder, immobilization with adhesive tape
On bar, rat head is more than 5cm apart from ground.6min is hung in test, and quiescent time is added up in 5min after record.
The measure of rat grip：By being placed on the grip plate of grip analyzer after right hand grasping rat, left hand is pushed away forward
Grip plate, then the right hand slide to rat-tail portion backward, left hand gently unclamps grip plate, treats that rat left side fore paw firmly catches grip
Reinforce post-tensioning during plate in time, determine the maximum grip of rat.Each zoometry three times, the grip averaged as the rat
Value.
The measure of neurotransmitter levels：Euthanasia simultaneously takes out rapidly brain, and the coronal partial application away from trailing edge 4mm, liquid nitrogen is solid
Change forebrain, -80 DEG C of preservations, HPLC combined with electrochemical detector determines monoamine neurotransmitters.
4. result of the test
The impact of 4.1 pairs of body weight
After modeling 4 weeks, compare with model group, positive drug group (BUCHANG NAOXINTONG JIAONANG) rat body weight amplification is apparently higher than mould
Type group (P<0.05), 2 groups of Chinese medicine composition of the present invention (0.30g/kg body weight), 3 groups of (0.60g/kg body weight) rat body weights are compared with mould
Type group weight, there is significant difference (P<0.05) 5, be the results are shown in Table.
Impact of the table 5 to type post-stroke depression rat model body weight
Note：Compare with model group：*P<0.05
The impact of 4.2 pairs of function of nervous system
Compare with model group, positive drug (BUCHANG NAOXINTONG JIAONANG) can substantially mitigate ischemic neurological symptom (P<0.05), originally
2 groups of invention Chinese medicine composition (0.30g/kg body weight) and 3 groups (0.60g/kg body weight) are significantly reduced ischemic neurological impairment property
(P<0.05).The results are shown in Table 6.
Impact of the table 6 to type post-stroke depression rat model function of nervous system
Note：Compare with model group：*P<0.05, * * P<0.01
The impact of 4.3 pairs of sucrose solution preferences
Before modeling, there was no significant difference between each group rat sucrose solution set of preferences；After modeling 4 weeks, model group rats sucrose solution preference
Decline, comparing with normal group has pole significant difference (P<0.01).The sucrose solution preference of each administration group rat all maintains raw water to put down substantially,
Comparing with model group has significant difference (P<0.05~0.01).The results are shown in Table 7.
Impact of the table 7 to sucrose solution preference
Note：Vs sham operated rats ##P<0.01；Vs model group * P<0.05,**P<0.01
The impact of 4.4 pairs of non-swimming times
Before modeling, there was no significant difference between the non-swimming time group of each group rat；After modeling 4 weeks, model group rats trip
The swimming dead time increases, and comparing with sham operated rats has pole significant difference (P<0.01).Compared with model group, positive drug group and this
The non-swimming time of bright each administration group rat is significantly reduced, and comparing with model group has significant difference (P<0.05~
0.01).The results are shown in Table 8.
Impact of the table 8 to non-swimming time
Note：Vs sham operated rats ##P<0.01；Vs model group * P<0.05,**P<0.01
The impact of 4.5 pairs of spacious field activity scores
Model group rats are reduced from exploratory behavior activity of advocating peace, and depressed lazy move, spacious field score is substantially less than sham operated rats.Give
After medicine 4 weeks, 2,3 groups of spacious field scores of positive drug group and Chinese medicine composition of the present invention are raised, and comparing with model group has significance poor
Different (P<0.05~0.01), 1 group of Chinese medicine composition only of the present invention is not improved.The results are shown in Table 9.
Impact of the table 9 to spacious field activity score
Note：Vs sham operated rats ##P<0.01；Vs model group * P<0.05,**P<0.01
The impact of 4.6 pairs of outstanding tail dead times
Before modeling, there was no significant difference between the non-swimming time group of each group rat；After modeling 4 weeks, model group rats hang
The tail dead time increases, and comparing with sham operated rats has pole significant difference (P<0.01).Compared with model group, positive drug group and this
The outstanding tail dead time of bright each administration group rat substantially shortens, and comparing with model group has significant difference (P<0.05~0.01).
The results are shown in Table 10.
The impact of 10 pairs, table outstanding tail dead time
Note：Vs sham operated rats ##P<0.01；Vs model group * P<0.05, * * P<0.01
The impact of 4.7 pairs of rat grips
Compared with rats in sham-operated group, model group rats grip reduces, difference extremely significantly (P<0.01).With model group rats
Compare, positive drug and each administration group rat grip of medicine of the present invention strengthen, wherein 1,2,3 groups of rats of Chinese medicine composition of the present invention
Grip there were significant differences (P<0.05~0.01), the results are shown in Table 11.
Impact of the table 11 to rat grip
Note：Vs sham operated rats ##P<0.01；Vs model group * P<0.05,**P<0.01
The measure of 4.8 neurotransmitter levels
Standard curve shows the linear relationship of norepinephrine (NE), dopamine (DA) and 5-hydroxy tryptamine (5-HT)：
NE:R=0.9983DA:R=0.9980,5-HT:R=0.9997, is respectively provided with good linear relationship, and by origin.Model
Monoamine neurotransmitter is reduced in group cerebral tissue, and comparing with sham operated rats has pole significant difference (P<0.01).With model group ratio
(P is dramatically increased compared with, positive drug group NE and 5-HT levels pole<0.01)；Chinese medicine composition of the present invention 2 groups of NE, levels are significantly raised
(P<0.01)；3 groups of NE, DA, 5-HT levels of Chinese medicine composition of the present invention significantly raise (P<0.01)；Chinese medicine composition of the present invention
1 group of NE, DA, 5-HT level is showed no and significantly changes.The results are shown in Table 12.
Impact of the table 12 to intracerebral neurotransmitter levels
Note：Vs sham operated rats ##P<0.01；Vs model group * P<0.05, * * P<0.01
5. conclusion
After giving rat medicine of the present invention, rat behavior has improvement, grip enhancing, intracerebral neurotransmitter levels to have not
Improve with degree, point out medicine of the present invention to play the role of to strengthen rats with stroke grip, improve type post-stroke depression.
In sum, medicine of the invention, to focal cerebral ischemia, permanent cerebral ischemia and type post-stroke depression, is respectively provided with
Significant curative effect, can effectively treatment cerebral infarction and the depression that is induced by it.
Claims (12)
1. a kind of Chinese medicine composition for treating cerebral infarction and type post-stroke depression, it is characterised in that the Chinese medicine composition by
The raw material of following weight portion composition is prepared：
Radix Ginseng 10-100 Folium Ginkgo 10-500 Radix Scutellariae 10-150
Fructus Gardeniae 10-200 Rhizoma Gastrodiae 10-200 Rhizoma Chuanxiong 10-200
Herba Hyperici perforati 10-200.
2. a kind of Chinese medicine composition for treating cerebral infarction and type post-stroke depression, it is characterised in that the Chinese medicine composition by
The raw material of following weight portion composition is prepared：
Radix Ginseng 10-100 Folium Ginkgo 10-500 Radix Scutellariae 10-150
Fructus Gardeniae 10-200 Rhizoma Gastrodiae 10-200 Rhizoma Chuanxiong 10-200
Herba Hyperici perforati 10-200 Radix Salviae Miltiorrhizae 10-200.
3. a kind of Chinese medicine composition for treating cerebral infarction and type post-stroke depression, it is characterised in that the Chinese medicine composition by
The raw material of following weight portion composition is prepared：
Radix Ginseng 10-100 Folium Ginkgo 10-500 Radix Scutellariae 10-150
Fructus Gardeniae 10-200 Rhizoma Gastrodiae 10-200 Rhizoma Chuanxiong 10-200
Herba Hyperici perforati 10-200 Radix Rhodiolae 10-200.
4. a kind of Chinese medicine composition for treating cerebral infarction and type post-stroke depression, it is characterised in that the Chinese medicine composition by
The raw material of following weight portion composition is prepared：
Radix Ginseng 10-100 Folium Ginkgo 10-500 Radix Scutellariae 10-150
Fructus Gardeniae 10-200 Rhizoma Gastrodiae 10-200 Rhizoma Chuanxiong 10-200
Herba Hyperici perforati 10-200 Radix Salviae Miltiorrhizae 10-200 Radix Rhodiolae 10-200.
5. Chinese medicine composition according to claim 1, it is characterised in that the Chinese medicine composition consists of the following parts by weight
Raw material prepare：
Radix Ginseng 10-50 Folium Ginkgo 10-250 Radix Scutellariae 10-100
Fructus Gardeniae 10-100 Rhizoma Gastrodiae 10-100 Rhizoma Chuanxiong 10-100
Herba Hyperici perforati 10-100.
6. Chinese medicine composition according to claim 2, it is characterised in that the Chinese medicine composition consists of the following parts by weight
Raw material prepare：
Radix Ginseng 10-50 Folium Ginkgo 10-250 Radix Scutellariae 10-100
Fructus Gardeniae 10-100 Rhizoma Gastrodiae 10-100 Rhizoma Chuanxiong 10-100
Herba Hyperici perforati 10-100 Radix Salviae Miltiorrhizae 10-100.
7. Chinese medicine composition according to claim 3, it is characterised in that the Chinese medicine composition consists of the following parts by weight
Raw material prepare：
Radix Ginseng 10-50 Folium Ginkgo 10-250 Radix Scutellariae 10-100
Fructus Gardeniae 10-100 Rhizoma Gastrodiae 10-100 Rhizoma Chuanxiong 10-100
Herba Hyperici perforati 10-100 Radix Rhodiolae 10-100.
8. Chinese medicine composition according to claim 4, it is characterised in that the Chinese medicine composition consists of the following parts by weight
Raw material prepare：
Radix Ginseng 10-50 Folium Ginkgo 10-250 Radix Scutellariae 10-100
Fructus Gardeniae 10-100 Rhizoma Gastrodiae 10-100 Rhizoma Chuanxiong 10-100
Herba Hyperici perforati 10-100 Radix Salviae Miltiorrhizae 10-100 Radix Rhodiolae 10-100.
9. the preparation method of the Chinese medicine composition as described in any one of claim 1-8, it is characterised in that comprise the following steps：
Whole crude drug are added water to cook after extraction gained extracting solution concentration plus ethanol precipitate with ethanol after crushing, and reclaim ethanol, are concentrated into thick
Cream, obtains final product the Chinese medicine composition.
10. preparation method according to claim 9, it is characterised in that comprise the steps：
Whole crude drug add water to cook extraction 2-4 time after crushing, each amount of water is 5-20 times of crude drug gross weight and measures, decocts every time
The time is boiled for 1-3h, merges decocting liquid, be concentrated into relative density 1.05-1.25, plus 95% ethanol precipitate with ethanol, place 12-24 hours,
Supernatant is taken, decompression recycling ethanol is concentrated into thick paste, obtains final product the Chinese medicine composition to without alcohol taste.
11. a kind of preparations for treating cerebral infarction and type post-stroke depression, it is characterised in that include just like right in the preparation
The Chinese medicine composition described in any one of 1-8 is required, or preparation method according to any one of claim 9-10 is obtained
Chinese medicine composition.
Chinese medicine composition described in 12. any one of claim 1-8 or the Chinese medicine group according to any one of claim 9-10
Purposes of the compound in the medicine for the treatment of cerebral infarction and type post-stroke depression is prepared.
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