CN1552415A - Medicine for treating dementia and preparing method thereof - Google Patents
Medicine for treating dementia and preparing method thereof Download PDFInfo
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- CN1552415A CN1552415A CNA031408435A CN03140843A CN1552415A CN 1552415 A CN1552415 A CN 1552415A CN A031408435 A CNA031408435 A CN A031408435A CN 03140843 A CN03140843 A CN 03140843A CN 1552415 A CN1552415 A CN 1552415A
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Landscapes
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Abstract
A Chinese medicine for treating chronic dementia, sanile dementia, vanular dementia and AD is prepared from 7 Chinese-medicinal materials including astragalus root, red sage root, Chuan-xiong rhizome, borneol, etc. Its advantages are high curative effect and quickly taking its effect.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of medicine for the treatment of dementia disease and preparation method thereof.
Background technology
Dementia is common senile disease, it also is the difficult treatment that current the world of medicine generally acknowledges, according to World Health Organization (WHO), among the old people of over-65s, people's intelligence generation obstacle of 10% is arranged, and wherein dementia takes place in 60% people, and along with the increasing of age, its dull-witted sickness rate is the trend that rises significantly.The dementia that geratic period takes place, the speed that develops according to symptom can divide chronic and acute two big classes: chronic dementia accounts for about 80% of senile dementia, is called senile chronic brain syndrome again.It comprises alzheimer disease, vascular dementia and both simultaneous Combination dementias.Also have some rare dementias in addition, as creutzfeldt-Jakob disease, parkinson etc.Psychoplegia is called old acute brain syndrome again, accounts for about 20% of whole dementias.This class dementia is secondary to general metabolism disorder, disease and drug intoxication and wound etc. more.It is many to cause that the dull-witted cause of disease has, and wherein main reason has two kinds---Alzheimer (AD) and vascular dementia (VD).Vascular dementia mainly is the dementia by caused by cerebrovascular disease.
Dull-witted is modal performance with memory disorder, secondly to suspect the symptom that occurs at first for it, along with PD, spirit is decline significantly, when the state of an illness further developed, computing capability went down, and also having cognitive disorder is that difficulty takes place in meticulous thinking, obstacle also takes place in the understanding, the judgement that develop into gradually daily life and general knowledge, this stage also aphasis can occur, and vocabulary reduces, the speech dullness, soliloquy maybe can not be told object names or total aphasia.Most patients also to the orientation force generation obstacle in time, personage and place, is not recognized the door, migration everywhere etc.Patients with terminal is liied in bed fully, and life is complete to be looked after by others, and the course of disease maintains about 50～ten years and dead.Vascular dementia is more common in about threescore, and the half patient has hypertension history.The state of an illness is ladder sample progress, be that apoplexy dementia symptom of every outbreak increases the weight of once, patient's emotion is emotional, hypomnesis, or symptoms such as headache, head sink, sleep disorder, cardiopalmus, inappetence are arranged, obvious dementia, rough, disorientation can appear late period.
Chinese medicine is included into senile dementia the category of " demented ", " melancholia ", " dementia ", thinks its sick position at brain, and the people is extremely old, deficiency of kidney-essence, and brain is become homeless foster, gives birth to dull-witted then.The channels of brains is parts of whole body channels, and the variation of its physiology, pathological change and whole body channels has something in common, but because of occupying unique status special pathological change is arranged.Tang's Sun Simiao " Qianjin Yao Fang moxibustion therapy door " cloud: " people god's institute annotates for a person, the head of body, the QI KOU shrewdness, and 365 networks belong to head on all." brain is tender dirty, the house of mental activity, the ground of spirit, the source of refreshing machine, the blood of the five internal organs elite, the clear positive depressed brain that converges at of six internal organs.First god of brain has commander's the five internal organs god's function.In addition, Chinese medicine is thought and people's spirit and consciousness activity though can belong to the five internal organs, is mainly belonged to the physiological function that The heart controls mental activities." element asks LINGLAN secret allusion quotation opinion " cloud: " heart person, the viscus likened to the monarch in the body also, here gods go out." " Ling Shu Miraculous Pivot or Divine Axis Benshen " cloud: " so appointing the heart of thing person meaning ".The people is to the old age, and brain is gradually empty, the function degradation; Marrow subtracts then that brain disappears, and dirtyly declines that then the defeated cloth in water Tianjin is not normal, and the deficiency of vital energy then blood operation is unable, gives birth in the phlegm-turbidity and blood stasis blood, and removing toxic substances is caused harm, and ruins body, and grandson's network superficial collaterals is obstructed; The brain network is impaired and knot stagnates, and is difficult the infiltrating irrigation QI and blood, and the lifting of key network is unfavorable, undermines heart and brain, and " the pure person's spirit of brains, assorted person is blunt." cause the mind to be become deaf, refreshing machine loses system, and memory is deficient, and the disturbance of intelligence of slow-witted and stupid takes place.
At present, the medicine of treatment senile dementia commonly used clinically, vascular dementia has cerebral vasodilator such as cinnarizine, ring almond fat (antithrombotic pill), flunarizine hydrochloride (flunarizine), nicotinic acid, papaverine, doubly his pyridine, pentoxifylline, nifedipine, rutin, low molecular dextran etc.; Cerebral metabolism is regulated medicine such as dihydroergotoxin (hydergine), duxil, piracetam, pyritionol hydrochloride neuroxin, meclofenoxane, huperzine is first-class; Anticoagulation medicine such as heparin, dicoumarol, acenocumarol tablet etc.; Thrombolytic agent such as streptokinase, urokinase etc.; Improve mental symptom medicine such as estazolam, ALprazolanic, roller, doxepin, thioridazine, haloperidol, promethazine etc.The effect of dementia symptom though the said medicine tool has some improvement, has certain curative effect clinically, but said medicine is because of absorbing and draining slowly, accumulate poisoning and side effect take place in life-time service easily, and can not fundamentally block the process of dementia or vascular dementia, the difficult healthy needs of human pursuit day by day that adapt to.And the Chinese medicine preparation of some treatment senile dementias, vascular dementia, disclose a kind of name on May last 1997 year 20 as the patented invention communique of Patent Office of the People's Republic of China and be called " a kind of medicine for the treatment of senile dementia and preparation method thereof ", application number 97116461.4, the patent application document of publication number CN1181966A; The patented invention communique of Patent Office of the People's Republic of China discloses a kind of name on June last 1993 year 9 and has been called " prescription of anti-encephalasthenia capsule and preparation technology ", the patent application document of application number 92114222.6, in these in the medicine preparation, used flavour of a drug are more, be difficult to control quality, the incompatibility industrialized great production of its medicine, in addition, existing Chinese medicine preparation is also lower in the curative effect of improving aspect the dementia symptom, is difficult to suppress the progress of dementia disease.
Therefore find that a kind of flavour of a drug are less, toxic and side effects is low, the pure Chinese medicinal preparation of evident in efficacy, short treating period, moderate cost, adaptation industrialized great production is particularly important.
Summary of the invention
Purpose of the present invention just provides a kind of more effective treatment dementia, chronic dementia, vascular dementia, senile dementia, Alzheimer, chronic cerebral dysfunction syndrome, learning and memory ability obstacle, the medicine of the disturbance of consciousness that cerebral thrombosis, cerebral arteriosclerosis, brain trauma, apoplexy, encephalitis cause.
Another object of the present invention has provided the preparation method of this medicine.
Medicament selection Radix Astragali air making-up and spleen enlivening of the present invention, helps blood to operate to monarch drug at kind big invigorating middle warmer gas, beneficial vigour and logical blood circulation regulating; Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong blood circulation and promoting silt, dredging the meridian, Rhizoma Atractylodis are drying damp and strengthening spleen, and the three is shared to be ministerial drug altogether; Rhizoma Coptidis, Rhizoma Acori Graminei, the refreshment that clears away heart-fire, the Fructus Alpiniae Oxyphyllae of having one's ideas straightened out are adjuvant drug; It is messenger drug that the Borneolum Syntheticum priming is gone into brain.All medicines share, and play inrigorating qi and promoting blood circulation, removing heat from the heart to restore the consciousness altogether, the merit of brain-care.Rhizoma Chuanxiong is the gas medicine in the blood in the side, " herbal classic " record, Rhizoma Chuanxiong " wind headache, arthralgia due to cold, spasm emergency, gold wound, married woman's blood close loss of fecundity in main ", adapted in the side of enriching blood, can sensible QI and blood can make tonify without causing stagnation, modern pharmacology proves, the effective ingredient ligustrazine can see through blood brain barrier in the Rhizoma Chuanxiong, remove vascular smooth muscle spasm, blood vessel dilating, improvement circulation that epinephrine causes, increasing blood flow speed, blood viscosity lowering improves blood microcirculation, improve blood supply insufficiency, specially good effect is arranged treating various blood supply insufficiency symptoms.More than all medicines, according to the rationale of science of TCM formulas, ingenious compatibility, tight combination is played the merit of inrigorating qi and promoting blood circulation, removing heat from the heart to restore the consciousness, brain-care altogether, thereby is reached to the purpose that heals.
The consumption of drug component of the present invention is also groped to sum up to draw through the inventor in a large number, and each amounts of components all has curative effect preferably in following ranges:
Radix Astragali 8.5-25.5 Radix Salviae Miltiorrhizae 8.5-25.5 Rhizoma Chuanxiong 5-15 Rhizoma Atractylodis 5-15
Rhizoma Acori Graminei 5-15 Rhizoma Coptidis 1.5-7.5 Borneolum Syntheticum 0.01-0.8.
Preferable range is:
Radix Astragali 12-20 Radix Salviae Miltiorrhizae 12-20 Rhizoma Chuanxiong 7-12 Rhizoma Atractylodis 7-12
Rhizoma Acori Graminei 7-12 2 Rhizoma Coptidis 2-5 Borneolum Syntheticum 0.03-0.08.
The best is:
The Radix Astragali 16.7 Radix Salviae Miltiorrhizaes 16.7 Rhizoma Chuanxiongs 10 Rhizoma Atractylodis 10 Rhizoma Acori Graminei 10 Rhizoma Coptidis 3.3 Borneolum Syntheticums 0.0667.
Medicine of the present invention can adopt the Chinese medicine preparation conventional method to be prepared into any conventional formulation.For example these crude drug pulverize mix homogeneously can be made powder takes after mixing it with water; Also can be with these medicines decocting together, the condensed water decocting liquid is made oral liquid then; But, preferably adopt following technology to extract, but this can not limit protection scope of the present invention to raw material in order to make each crude drug of this medicine better bring into play drug effect.
The preparation method of medicine of the present invention is as follows:
Weigh following raw materials according by weight percentage
Radix Astragali 8.5-25.5 Radix Salviae Miltiorrhizae 8.5-25.5 Rhizoma Chuanxiong 5-15 Rhizoma Atractylodis 5-15
Rhizoma Acori Graminei 5-15 Rhizoma Coptidis 1.5-7.5 Borneolum Syntheticum 0.01-0.8;
(1): the Radix Astragali, Radix Salviae Miltiorrhizae add 6-14 times of water gaging, reflux, extract, 1-4 time, and each 0.5-3 hour, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 6-14 times of water gaging and extracted volatile oil 4-12 hour with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 6-14 times of water gaging again and extracted 0.5-3 hour, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 0.5-3g crude drug, cool, add 86-99% ethanol, making determining alcohol is 70-85%, after the standing over night, filter, reclaim ethanol and approximate the 1-5g crude drug, adding 86-99% ethanol to 1ml, making determining alcohol is 70-85%, after the standing over night, filter, reclaim ethanol, under 40-80 ℃ of condition, concentrate out cream, to relative density 1.10～1.45;
(2): Rhizoma Coptidis adds 4-12 and doubly measures the 50-95% alcohol reflux 1-4 time, and each 1-4 hour, merge extractive liquid,, filter, reclaim ethanol and be about the 0.1-0.5g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,0-8 ℃ of cold preservation is spent the night, filter, filter cake repeatedly washs with distilled water, 60-90 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves.
(3): get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, add 1～6 times of total extractum amount, 60-90 ℃ fused polyethylene glycol 6000, stir, add mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, it is even to change material at 60～95 ℃, promptly gets active component;
(4): this active component can add suitable adjuvant, makes tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid on the pharmaceutics, sucks agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, spray, drop pill etc.
Preferably, the prescription of medicine of the present invention and preparation method are as follows:
Weigh following raw materials according by weight percentage: Radix Astragali 12-20 Radix Salviae Miltiorrhizae 12-20 Rhizoma Chuanxiong 7-12 Rhizoma Atractylodis 7-12
Rhizoma Acori Graminei 7-12 Rhizoma Coptidis 2-5 Borneolum Syntheticum 0.03-0.08;
(1): the Radix Astragali, Radix Salviae Miltiorrhizae add 8-12 times of water gaging, reflux, extract, 1-3 time, and each 1-2 hour, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 8-12 times of water gaging and extracted volatile oil 6-10 hour with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 8-12 times of water gaging again and extracted 1-2 hour, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 0.8-1.5g crude drug, cool, add 90-96% ethanol, making determining alcohol is 75-83%, after the standing over night, filter, reclaim ethanol and approximate the 2-4g crude drug, adding 90-96% ethanol to 1ml, making determining alcohol is 75-83%, after the standing over night, filter, reclaim ethanol, under 55-65 ℃ of condition, concentrate out cream, to relative density 1.20～1.35;
(2): Rhizoma Coptidis adds 6-10 and doubly measures 70-80% alcohol reflux twice, and each 1-3 hour, merge extractive liquid,, filter, reclaim ethanol and be about the 0.2-0.4g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,3-6 ℃ of cold preservation is spent the night, filter, filter cake repeatedly washs with distilled water, 75-85 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves.
(3): get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, add 2.5～3.5 times of total extractum amounts, 75-85 ℃ fused polyethylene glycol 6000, stir, add mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, it is even to change material at 70～90 ℃, promptly gets active component;
(4): this active component can add suitable adjuvant, makes tablet on the pharmaceutics, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, granule, electuary, pill, powder, unguentum, suspensoid, powder, solution, ointment, plaster, drop pill etc.
Best, the prescription and the preparation method of medicine of the present invention are as follows:
The Radix Astragali 16.7 Radix Salviae Miltiorrhizaes 16.7 Rhizoma Chuanxiongs 10 Rhizoma Atractylodis 10 Rhizoma Acori Graminei 10 Rhizoma Coptidis 3.3 Borneolum Syntheticums 0.0667;
(1): the Radix Astragali, Radix Salviae Miltiorrhizae add 10 times of water gagings, reflux, extract, 2 times, and each 1.5 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei add 10 times of water gagings and extracted volatile oil 8 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 10 times of water gagings again and extracted 1.5 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 1g crude drug, cool, add 95% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 3g crude drug to 1ml, add 95% ethanol, making determining alcohol is 80%, after the standing over night, filter, reclaim ethanol, concentrate out cream, 60 ℃ of conditions down to relative density 1.25～1.33;
(2): Rhizoma Coptidis adds 8 times of amount 75% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.3g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,5 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves.
(3): get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, add 2.5～3.5 times of total extractum amounts, 80 ℃ of fused polyethylene glycol 6000s, stir, add mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, it is even to change material at 80～85 ℃, drip system at 80-85 ℃, promptly get drop pill.
In medication preparation of the present invention, the adjuvant of adding can be: starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, gelatin, glycerol, agar, calcium carbonate, surfactant, Polyethylene Glycol, dextrin etc.; Made dosage form can be: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, spray, drop pill etc., preferably capsule, granule, tablet, oral liquid, drop pill, pill etc.
More than form when producing and to increase or to reduce according to corresponding ratio, as large-scale production can be unit with kilogram or with the ton, small-scale production can be unit with the gram also, and weight can increase or reduce, but the crude drug material weight proportion constant rate between each composition.
More than each single medicinal material, especially adjuvant drug, messenger drug or adjuvant drug and messenger drug in forming, can be replaced by suitable Chinese medicine individually or simultaneously with the identical property of medicine, effect, it is constant to replace back Chinese medicine preparation and drug effect thereof.
Medicine of the present invention can be determined usage and dosage according to patient's situation in use, but every day 1-3 time, and every day, each crude drug consumption was as the criterion with the state-promulgated pharmacopoeia dosage, was no more than the pharmacopeia ormal weight.
The present invention be at distinguished veteran doctors of TCM on the basis of proved recipe, through a large amount of preparation technology's test and pharmacology, the resulting preparation of pharmacodynamics test.The present invention is evident in efficacy, effect with inrigorating qi and promoting blood circulation, removing heat from the heart to restore the consciousness, brain-care, dredging the meridian, be applicable to dementia, chronic dementia, vascular dementia, senile dementia, Alzheimer, chronic cerebral dysfunction syndrome, learning and memory ability obstacle, the patient of the disturbance of consciousness that cerebral thrombosis, cerebral arteriosclerosis, brain trauma, apoplexy, encephalitis cause.
Reasonable recipe of the present invention, poisonous side effect of medicine is low, overcome the western medicine dementia, chronic dementia, vascular dementia, senile dementia, Alzheimer, chronic cerebral dysfunction syndrome, learning and memory ability obstacle, the toxic and side effects of the disturbance of consciousness that cerebral thrombosis, cerebral arteriosclerosis, brain trauma, apoplexy, encephalitis cause is big, expense is high, the Chinese medicine curative effect is low, flavour of a drug are many, the shortcoming of incompatibility large-scale production, is the medicine of the treatment senile dementia determined of a kind of economy, material benefit, curative effect, vascular dementia, cerebral infarction, apoplexy sequela.
For a better understanding of the present invention, below by experiment example further set forth the beneficial effect of invention medicine, experimental example comprises the pharmacodynamics animal experiment of medicine of the present invention (to call XINGNAO DIWAN in the following text).Test is intended to further specify the effect of XINGNAO DIWAN below, but not limitation of the present invention.The invention medicine that this experimental example adopts is to be prepared from by embodiment 1.
[experimental example]
1. XINGNAO DIWAN is to the influence of bilateral common carotid arteries permanent ligation learning and memory in rats ability and cerebral tissue pathomorphology
Adopt ligation rat bilateral common carotid arteries to cause intraluminal middle cerebral artery occlusion in rats thrombosis (Middle Cerebral ArteryThrombosis, MCAT) method of model is observed behind the ligation bilateral common carotid arteries influence to learning and memory in rats ability and cerebral tissue pathomorphology.Measure the resolution learning capacity with water maze test (Water maze).Adopt mice water maze (structure of water maze is seen Fig. 1 with the rat water maze), the 46th day begins training after modeling, administration, and condition is controlled at 22 ± 2 ℃ of room temperatures, and 25 ± 1 ℃ of water temperatures are about depth of water 10cm.Experiment divides to be carried out in 3 days, the 1st day training A point 1 time and B point 3 times; Surveyed the B point on the 2nd day, training C point 3 times; Surveyed the C point on the 3rd day.The training time that A, B are ordered is limited in the 2min, and the C point is limited in the 4min, and overtime person is respectively by 2min and 4min.Every each training and testing of mice all writes down time (time of advent) of reaching home and the number of times (errors number) that enters cecum.With training period B, C 2 times of advent and errors number as school grade; With testing period B, C 2 times of advent and errors number as the memory achievement.Result of the test SPSS software statistics relatively, is carried out the t check between group.
Adopt the true coloured picture picture analysis of C8 system that cerebral cortex choline acetyltransterase (ChAT), Brain Derived Neurotrophic Factor (BDNF), glial fibrillary acidic protein (GFAP) positive cell are carried out Measurement and analysis, get 4 rats at random for every group, every rat is got 3 sections at random, 3 visuals field of every section random observation, write down the surface density of each statistics field, result's SPSS software statistics relatively, is carried out the t check between group.
Result of the test shows, XINGNAO DIWAN (0.4g/kg, 0.2g/kg, 0.1g/kg) each organize through successive administration after 40 days, all can improve the learning and memory function obstacle that the ligation bilateral common carotid arteries caused in 40 days, show as in the water maze test, the time of each point training and testing shortens, errors number reduces, and compares with model group that there were significant differences (P＜0.05, P＜0.01).XINGNAO DIWAN (0.4g/kg, 0.2g/kg, 0.1g/kg) each organize through successive administration after 44 days, all can improve rat cerebral tissue's pathomorphology change that the ligation bilateral common carotid arteries caused in 44 days, three dosage groups all can make the choline acetyltransterase (ChAT) of expressing to weaken strengthen, 0.4g/kg, 0.1g/kg group can make and express the Brain Derived Neurotrophic Factor (BDNF) that weakens and strengthen, 0.4g/kg group can make the enhanced glial fibrillary acidic protein of expression (GFAP) weaken, compare with model group that there were significant differences (P＜0.05, P＜0.01).
2. XINGNAO DIWAN is induced the influence of brain function decline ability of learning and memory in mice and cerebral tissue radical damage to the D-galactose
Adopt mice every day in the subcutaneous injection D-of nape portion galactose (D-gal) 100mg/kg, be mixed with the solution of 100mg/10ml with 0.9% normal saline, volumetric injection is 0.1ml/10g, and give once every day.The blank group is total to modeling 49 days in isometric 0.9% normal saline of nape portion subcutaneous injection every day.Measure the resolution learning capacity with water maze test (Water maze).Adopt mice water maze (structure of water maze is seen Fig. 1 with the rat water maze), the 46th day begins training after modeling, administration, and condition is controlled at 22 ± 2 ℃ of room temperatures, and 25 ± 1 ℃ of water temperatures are about depth of water 10cm.Experiment divides to be carried out in 3 days, the 1st day training A point 1 time and B point 3 times; Surveyed the B point on the 2nd day, training C point 3 times; Surveyed the C point on the 3rd day.The training time that A, B are ordered is limited in the 2min, and the C point is limited in the 4min, and overtime person is respectively by 2min and 4min.Every each training and testing of mice all writes down time (time of advent) of reaching home and the number of times (errors number) that enters cecum.With training period B, C 2 times of advent and errors number as school grade; With testing period B, C 2 times of advent and errors number as the memory achievement.Result of the test SPSS software statistics relatively, is carried out the t check between group.
XINGNAO DIWAN is to the mensuration of the influence of cerebral tissue radical damage, employing is with the preparation method of mouse brain tissue homogenate: mice the 49th day broken end after modeling, administration got brain, decerebellation, olfactory bulb add the homogenate in 4 ℃ of environment of 9 times of ice-cold normal saline, the tissue homogenate of preparation 10%.The assay method of protein, SOD, MDA and GSH: build up the test kit explanation strictness that bio-engineering research provides by Nanjing and operate.
Result of the test shows that D-galactose nape portion subcutaneous injection can cause the learning and memory of little mouse dysfunction in 46 days, showed as in the water maze test, the time lengthening of each point training and testing, errors number increases, and has compared notable difference (P＜0.05, P＜0.01) with the blank group.XINGNAO DIWAN (0.52g/kg, 0.26g/kg, 0.13g/kg) each organize through successive administration after 46 days, all can improve this learning memory disorder, show as in the water maze test, the time of each point training and testing shortens, errors number reduces, compared notable difference (P＜0.05, P＜0.01) with model group.The subcutaneous injection D-of nape portion galactose can cause mouse brain to organize radical damage in 49 days, showed as that the SOD vigor obviously descends in the cerebral tissue, and MDA content significantly increases, and GSH content obviously reduces, and has compared notable difference (P＜0.01) with the blank group.Each group of XINGNAO DIWAN (0.52g/kg, 0.26g/kg, 0.13g/kg) all can alleviate this radical damage, shows as the SOD vigor in the cerebral tissue that improves, and reduces MDA content, increases GSH content, compares significant difference (P＜0.01) with model group.
3. XINGNAO DIWAN is induced the influence of middle cerebral artery thromboembolia type rat ischemia brain injury to ferric chloride
Ferric chloride induces the preparation method of middle cerebral artery thromboembolia type rat ischemia brain damage model as follows: rat is with 10% chloral hydrate (350mg/kg) intraperitoneal injection of anesthesia, left lateral position is fixed, curved incision at right side paropia and external auditory meatus line mid point work one long 1.5cm, pinch off is also removed temporalis, expose temporal bone, make the bone window of a diameter 2.5mm at cheekbone and temporo squamosum joint to nasal side 1mm place with dental burr, expose middle cerebral artery, suction is had 10ul 50%FeCl
3The small pieces filter paper of liquid applies on middle cerebral artery, and operation is carried out under stereomicroscope.Treat medium-sized artery blackening behind the 30min, take off filter paper, layer-by-layer suture.Sham operated rats is not applied FeCl
3, surplus same model group.
The nervous symptoms methods of marking is improved with reference to the method for Bederson etc., respectively the nervous symptoms of animal is marked in postoperative 24h, 48h, and standards of grading are as follows: 1. rat is carried tail when unsettled, two forelimb symmetries are stretched to ground, remember 0 fen,, remember 1 fen as not parallel; 2. put rat on plastic plate, make it to front slide 10cm, promote resistance about feel and equate, remember 0 fen, otherwise remember 1 fen in the back reinforcing of Mus shoulder; 3. animal two forelimbs are put on the wire netting, firmly pulled back, observe two muscle of anterior limb tension force, equity and strong person remember 0 fen, and operation offside muscle of anterior limb tension force descender remembers 1 fen; 4. animal have do not stop to the operation offside person of turn-taking, remember 1 fen.Go up according to this standard, full marks 4 minutes, mark is high more, and the animal behavior obstacle is serious more.Result's SPSS software statistics relatively, is carried out the t check between group.
Result of the test shows that each group of XINGNAO DIWAN (0.6g/kg, 0.3g/kg) behind successive administration 7 times, can significantly reduce the scoring of middle cerebral artery thromboembolia type rat nervous symptoms, obviously lowers the cerebral infarction ratio; XINGNAO DIWAN 0.6g/kg group can obviously lower brain water content, compares with model group that there were significant differences (P＜0.05, P＜0.01).This kind results suggest medicine has the effect that improves cerebral ischemia.
XINGNAO DIWAN to 8 ℃ of frozen water of mice swimming time-to-live, frozen water swimming 5min after the influence of broken end mouth breathing time and cerebral tissue energy metabolism and anoxia biochemical indicator
The mensuration of 8 ℃ of frozen water swimming time-to-live of mice adopts following method: apart from the about 2cm in mouse tail tip place is the rubber mud ball of one 10% body weight, putting into 8 ± 0.5 ℃ frozen water swims, one every barrel, observe and write down mice from putting into water to dead this section period.If surpass 16 minutes, then in 16 minutes.Result's SPSS software statistics relatively, is carried out the t check between group.
Behind 8 ℃ of frozen water of mice swimming 5min the broken end mouth breathing time mensuration adopt following method: apart from the about 2cm in mouse tail tip place is the rubber mud ball of about 10% body weight, puts into and takes out from frozen water after 8 ± 0.5 ℃ frozen water was swum 5 minutes.Break end rapidly in its ears rear, observe and record from the broken end beginning to its time of stopping of breathing for the last time as the broken end mouth breathing time.Result's SPSS software statistics relatively, is carried out the t check between group.
The mensuration of cerebral tissue energy metabolism and anoxia biochemical indicator adopts following method behind 8 ℃ of frozen water swimming of mice 5min: after measuring the broken end mouth breathing time, on 4 ℃ of ice pans, get brain rapidly, decerebellation, olfactory bulb add 9 times of ice-cold normal saline and be prepared into 10% brain homogenate liquid under 4 ℃ of environment.Albumen, LA, LDH and ATP enzyme activity determination method are all built up the test kit explanation of bio-engineering research institute in strict accordance with Nanjing and are operated.
Each group of XINGNAO DIWAN (0.8g/kg, 0.4g/kg, 0.2g/kg) all can obviously prolong the time-to-live that mice is swum through successive administration after 4 days in frozen water, compared notable difference (P＜0.05, P＜0.01) with model group; Three dosage groups all can obviously prolong the mice frozen water swimming back broken end mouth breathing time, compared notable difference (P＜0.05 with model group, P＜0.01), three dosage groups all can obviously be resisted frozen water swimming and cause mouse brain and organize lactic acid (LA) content to increase lactic acid dehydrogenase (LDH), Na
+-K
+-ATP enzyme and Ca
2+-Mg
2+-ATP enzyme activity descends, and compares with model group that there were significant differences (P＜0.05, P＜0.01).
5. XINGNAO DIWAN is to FeCl
3Induce the influence of focal cerebral ischemia rat brain blood flow rate
Rat is used in experiment, and with 10% chloral hydrate (350mg/kg) intraperitoneal injection of anesthesia, the ventricumbent position is fixed, and cuts calvarium center skin, separates subcutaneous tissue.The bone window that a diameter is about 0.5cm is made a call to dental burr by about to the right 0.2mm place in calvarium posterior center, removes pia mater encephali, exposes cerebral tissue.Rat is fixed on the stereotaxic instrument, the laser probe of laser-Doppler tissue blood flow analyzer is placed about 2mm place, cranium window surface, trace blood flow, the result directly imports computer.By the time after blood flow is stablized about 5 minutes, trace the FeCl of the cerebral tissue surface dropping 10% at place at laser microprobe with microsyringe
35 μ l.Observe altogether and trace 60 minutes.Experimental result SPSS software statistics relatively, is carried out the t check between group.
Adopt the result of laser tissue measuring of blood flow instrument research to show, after 4 days, each group of XINGNAO DIWAN (0.6g/kg, 0.3g/kg, 0.15g/kg) all can significantly be improved FeCl through successive administration
3Inductive cerebral tissue blood flow rate descends, and shows as to make to drip FeCl
3The percentage rate that back 30-50min blood flow rate descends reduces; Two groups of XINGNAO DIWAN (0.6g/kg, 0.3g/kg) can also make blood flow rate 50% time lengthening that need that descend, and compare with model group that there were significant differences (P＜0.05, P＜0.01).
6. XINGNAO DIWAN is to the influence of bilateral ligation rat cerebral tissue vascular permeability
Rat is with 10% chloral hydrate (350mg/kg) intraperitoneal injection of anesthesia, and dorsal position is fixed, and cuts neck center skin, separates bilateral common carotid arteries, sunkens cord.Sublingual vein injects azovan blue, and (Evans Blue, EB), volume is 0.2ml/100g (EB is made into 2.5% normal saline solution).Ligation bilateral common carotid arteries immediately after 5 minutes, skin suture, routine disinfection.Sham operated rats is only separated bilateral common carotid arteries, not ligation.Performed the operation back 6 hours, the sacrificed by decapitation animal is got brain, removes olfactory bulb, cerebellum and low brain stem.
The result shows, behind the ligation bilateral common carotid arteries 6 hours, rat cerebral tissue's vascular permeability significantly increased, and shows as that azovan blue content increases in the cerebral tissue, compared notable difference (P＜0.05) with sham operated rats.Each group of XINGNAO DIWAN (0.6g/kg, 0.3g/kg, 0.15g/kg) and hydergine group (0.8mg/kg) through prevent administration after 3 days the increase to the cerebral tissue vascular permeability improvement effect is all arranged, show as and make azovan blue content reduction in the cerebral tissue, compared notable difference (P＜0.05, P＜0.01) with model group.Illustrate that the cerebral tissue vascular permeability that XINGNAO DIWAN can be improved due to the cerebral ischemia increases, the protection blood brain barrier, thus ensure the stable of environment in the central nervous tissue, safeguard its normal function.
7. XINGNAO DIWAN is moved-the thrombotic influence of vein bypass rat
Rat is used in experiment, lumbar injection 10% chloral hydrate 350mg/kg anesthesia, dorsal position is fixed, operation, separate right common carotid artery and left external jugular vein, three sections polyethylene tubes are linked to each other, and an end inserts right common carotid artery, and the other end inserts left external jugular vein, interlude is put into No. 7 surgical threads of a long 8cm, heavily about 8mg fills with 5u/ml heparin-saline solution in the pipe, set up the artery and vein bypass.Take off sleeve pipe behind the 15min, removal of thromboses rolls on moistening filter paper, removes unnecessary floating blood, weigh wet weight of thrombus; Put 60 ℃ of oven for drying then to constant weight, take by weighing the dry weight of thrombosis after the cooling immediately.Experimental result SPSS software statistics relatively, is carried out the t check between group.
XINGNAO DIWAN 0.6g/kg and 0.3g/kg group all can obviously reduce the weight in wet base and the dry weight of moving-vein bypass thrombosis, compares with model group that there were significant differences (P＜0.01).Illustrate that XINGNAO DIWAN has obvious antithrombotic effect.
8. thrombolytic effect in the XINGNAO DIWAN body
Rat is used in experiment, lumbar injection 10% chloral hydrate 0.35g/kg anesthesia, and dorsal position is fixed, and separates left carotid, and the thrombosis detector stimulating electrode is put in the common carotid artery proximal part, and thermosensitive thermometer is put in distal end, with 1.5mA galvanism 7min.Take off stimulating electrode and thermal detector, then disinfection and stitching.Second day gastric infusion as stated above, 1h after the last administration, with rat anesthesia, operation, the careful complete common carotid artery section that contains thrombosis of cutting, it is fixing to put into 10% formalin, take out vascular thrombosis behind the 2h and be put on the filter paper, the flush away excessive moisture is accurately measured thrombosis length, get the long thrombosis of 0.5cm then and weigh, experiment is an index with thrombosis length and weight.
Computing formula: thrombus weight (10-4g)=thrombosis and blood vessel weight-blood vessel weight
Experimental result SPSS software statistics relatively, is carried out the t check between group.
Result of the test shows, XINGNAO DIWAN 0.6g/kg group can obviously reduce thrombosis length, alleviates thrombus weight, compares with model group that there were significant differences (P＜0.01); XINGNAO DIWAN 0.3g/kg group can obviously reduce thrombosis length, compares with model group that there were significant differences (P＜0.05), and thrombus weight is not had influence; XINGNAO DIWAN 0.15g/kg group does not then all have obvious influence to thrombosis length and weight.The result proves that further XINGNAO DIWAN has antithrombotic effect.
9. XINGNAO DIWAN is to the influence of acute stress hemorheology of rat
Rat is adopted in experiment, is divided into six groups at random, and except that sham operated rats subcutaneous injection NS 0.1ml/kg, all the other respectively organize subcutaneous injection adrenalin hydrochloride (Adr) 0.1mg/kg, behind the 2h, soak 5min in 8 ℃ of frozen water, behind the 2h, gives and Adr 0.1mg/kg again.
Dosage is respectively 0.6g/kg, 0.3g/kg and 0.15g/kg to the administration group with the XINGNAO DIWAN gastric infusion every day; Sham operated rats and model group gavage 0.5% sodium carboxymethyl cellulose (CMC-Na).Divide 2 gastric infusions of upper and lower noon every day, give 1ml/100g at every turn, modeling behind the successive administration 5 times, modeling is administration again after 24 hours, after the administration 1 hour, gets blood, and measures every index.Behind the modeling 24h, with 10% chloral hydrate 0.35ml/100g intraperitoneal injection of anesthesia, common carotid artery blood sampling is positioned over the detection of carrying out every index in the test tube of heparinization with rat.
(1) blood sampling 0.04ml adds red cell deformability reagent 1ml mixing, and sampling 0.8ml surveys erythrocytic morphotropism.
(2) blood sampling 0.8ml surveys erythrocytic aggregation.
(3) blood sampling 0.8ml, the survey shear rate is 200s
-1, 30s
-1, 5s
-1And 1s
-1Whole blood viscosity.
(4) get the residue blood sample, 3000 rev/mins centrifugal 8 minutes, get blood plasma 0.8ml, the survey shear rate is 100s
-1Plasma viscosity.
Result of the test shows, XINGNAO DIWAN 0.3g/kg group can improve stasis syndrome rat model erythrocyte deformability, compare with model group that there were significant differences (P＜0.05), XINGNAO DIWAN 0.3g/kg group and 0.6g/kg organize can reduce stasis syndrome rat model erythrocyte aggregation ability, compares with model group that there were significant differences (P＜0.01).Each group of XINGNAO DIWAN all has obvious reduction effect to the high, medium and low shear rate of stasis syndrome rat model whole blood viscosity, has compared notable difference (P＜0.05, P＜0.01) with model group.
10. XINGNAO DIWAN is to the influence of frozen water swimming mouse blood coagulability
Mice is adopted in test, is the plasticine of one 10% body weight apart from the about 2cm in mouse tail tip place, puts into 8 ± 0.5 ℃ frozen water and swims 7 minutes, and one every barrel, taking-up places room temperature (21 ℃) to measure blood time and clotting time after 1 hour.
The mensuration of bleeding time and clotting time: after the mouse tail tip cut off by unified diameter position, the tail tip placed 37 ± 0.5 ℃ normal saline, observes the also record bleeding time.After getting blood with glass capillary from the endocanthion of mice, the two ends blood capillary that fractures is respectively observed also record clotting time.
Result of the test shows that XINGNAO DIWAN (0.8g/kg, 0.4g/kg) group can obviously prolong the mice frozen water swimming back bleeding time, compares with model group to have significant difference (P＜0.05, P＜0.01); Each administration group of XINGNAO DIWAN (0.8g/kg, 0.4g/kg., 0.2g/kg) all can obviously prolong mice frozen water swimming back clotting time, compares with model group to have significant difference (P＜0.05, P＜0.01).
11, the toxicological study of refreshment brain drop pill
Acute toxicity test: this test selects for use Kunming kind white mice as experimental animal, adopts the gastric infusion approach, has observed the acute toxic reaction after the XINGNAO DIWAN single gives animal, and has measured the LD50 value.The result shows, calculates the LD of XINGNAO DIWAN gastric infusion with the Bliss method
50The dose 102.33g/kg that makes a living is equivalent to 307 times of clinical daily dosage, its 95% credible 90.01～116.42g/kg that is limited to.The result shows that this medicine is safer.
Long term toxicity test: the SD rat is adopted in this test, give XINGNAO DIWAN to irritate the stomach approach, continuous irrigation stomach 6 months, dosage is 20,10,5g crude drug/kg day, be respectively 60,30,15 times of human dosage, the result does not see drug-induced toxic reaction, illustrates that the long-term gastric infusion of this product is safer.
Description of drawings:
Fig. 1 is the water maze structure chart that uses in the middle of the influence of experimental example XINGNAO DIWAN to bilateral common carotid arteries permanent ligation learning and memory in rats ability and cerebral tissue pathomorphology, wherein the starting point of A, B, C representative swimming circuit; 1,2,3,4 represents cecum; L represents step.
Specific embodiment
The present invention will be further described below in conjunction with embodiment, and following each embodiment only is used to the present invention is described and is not limitation of the present invention.
Embodiment 1: the preparation of drop pill
The raw material of Chinese medicine of getting selected following weight is standby through screening, purify, pulverizing:
Radix Astragali 16.7g, Radix Salviae Miltiorrhizae 16.7g, Rhizoma Chuanxiong 10g, Rhizoma Atractylodis 10g, Rhizoma Acori Graminei 10g, Rhizoma Coptidis 3.3g, Borneolum Syntheticum 0.0667g;
Get the Radix Astragali, Radix Salviae Miltiorrhizae adds 10 times of water gagings, reflux, extract, 2 times, each 1.5 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 10 times of water gagings and extracted volatile oil 8 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 10 times of water gagings again and extracted 1.5 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 1g crude drug, cool, add 95% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 3g crude drug to 1ml, add 95% ethanol, making determining alcohol is 70%, after the standing over night, filter, reclaim ethanol, concentrate out cream, under 60 ℃ of conditions, be concentrated into relative density 1.25～1.33; Rhizoma Coptidis adds 10 times of amount 75% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.3g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,5 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
Get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, adds mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, and it is even to change material at 80～85 ℃, makes active component of the present invention;
Adding temperature in the above-mentioned active component is 80 ℃, measures in 2.5～3.5 times of fused polyethylene glycol 6000s of total extractum amount, stir, move in the drop pill machine, drip system, get 1000 of drop pills at 80～85 ℃.
Embodiment 2: the preparation of granule
The raw material of Chinese medicine of getting selected following weight is standby through screening, purify, pulverizing:
Radix Astragali 25.5g, Radix Salviae Miltiorrhizae 25.5g, Rhizoma Chuanxiong 15g, Rhizoma Atractylodis 15g, Rhizoma Acori Graminei 15g, Rhizoma Coptidis 7.5g, Borneolum Syntheticum 0.8g;
Get the Radix Astragali, Radix Salviae Miltiorrhizae adds 14 times of water gagings, reflux, extract, 2 times, each 3 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 12 times of water gagings and extracted volatile oil 12 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 12 times of water gagings again and extracted 3 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 1.5g crude drug, cool, add 98% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 4g crude drug to 1ml, add 95% ethanol, making determining alcohol is 70%, after the standing over night, filter, reclaim ethanol, concentrate out cream, under 60 ℃ of conditions, be concentrated into relative density 1.10～1.45; Rhizoma Coptidis adds 12 times of amount 95% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.5g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,8 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 70 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
Get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, adds mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, and it is even to change material at 60～90 ℃, makes active component of the present invention;
With adding suitable adjuvant in the above-mentioned active component, stir, make 500 bags of granules.
Embodiment 3: the preparation of capsule
The raw material of Chinese medicine of getting selected following weight is standby through screening, purify, pulverizing:
Radix Astragali 8.5g, Radix Salviae Miltiorrhizae 8.5g, Rhizoma Chuanxiong 5g, Rhizoma Atractylodis 5g, Rhizoma Acori Graminei 5g, Rhizoma Coptidis 2g, Borneolum Syntheticum 0.01g;
Get the Radix Astragali, Radix Salviae Miltiorrhizae adds 8 times of water gagings, reflux, extract, 2 times, each 2 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 8 times of water gagings and extracted volatile oil 4 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 10 times of water gagings again and extracted 2 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 0.5g crude drug, cool, add 90% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 3g crude drug to 1ml, add 95% ethanol, making determining alcohol is 80%, after the standing over night, filter, reclaim ethanol, concentrate out cream, under 60 ℃ of conditions, be concentrated into relative density 1.25～1.33; Rhizoma Coptidis adds 8 times of amount 90% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.2g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,0 ℃ of cold preservation is spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
Get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, adds mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, and it is even to change material at 80～85 ℃, makes active component of the present invention;
With adding appropriate amount of starch in the above-mentioned active component, stir, make 500 of capsules.
Embodiment 4: the preparation of soft capsule
The raw material of Chinese medicine of getting selected following weight is standby through screening, purify, pulverizing:
Radix Astragali 20g, Radix Salviae Miltiorrhizae 20g, Rhizoma Chuanxiong 12g, Rhizoma Atractylodis 12g, Rhizoma Acori Graminei 12g, Rhizoma Coptidis 5g, Borneolum Syntheticum 0.08g;
Get the Radix Astragali, Radix Salviae Miltiorrhizae adds 10 times of water gagings, reflux, extract, 2 times, each 2.5 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 10 times of water gagings and extracted volatile oil 4 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 10 times of water gagings again and extracted 2.5 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 1g crude drug, cool, add 90% ethanol, making determining alcohol is 70%, after the standing over night, filter, reclaim ethanol and approximate the 2g crude drug to 1ml, add 95% ethanol, making determining alcohol is 70%, after the standing over night, filter, reclaim ethanol, concentrate out cream, under 60 ℃ of conditions, be concentrated into relative density 1.25～1.33; Rhizoma Coptidis adds 10 times of amount 75% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.3g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,5 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
Get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, adds mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, and it is even to change material under 80～85 ℃ of conditions, makes active component of the present invention;
To add appropriate amount of auxiliary materials in the above-mentioned active component, make 1000 of soft capsules.
Embodiment 5: the preparation of tablet
The raw material of Chinese medicine of getting selected following weight is standby through screening, purify, pulverizing:
Radix Astragali 12g, Radix Salviae Miltiorrhizae 12g, Rhizoma Chuanxiong 7g, Rhizoma Atractylodis 7g, Rhizoma Acori Graminei 7g, Rhizoma Coptidis 2g, Borneolum Syntheticum 0.03g;
Get the Radix Astragali, Radix Salviae Miltiorrhizae adds 6 times of water gagings, reflux, extract, 2 times, each 1 hour, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 6 times of water gagings and extracted volatile oil 5 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 8 times of water gagings again and extracted 1.5 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 1.5g crude drug, cool, add 95% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 3g crude drug to 1ml, add 95% ethanol, making determining alcohol is 70%, after the standing over night, filter, reclaim ethanol, concentrate out cream, under 60 ℃ of conditions, be concentrated into relative density 1.20～1.40; Rhizoma Coptidis adds 5 times of amount 80% alcohol reflux twice, each 4 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.5g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,5 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
Get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, adds mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, and it is even to change material at 80～85 ℃, makes active component of the present invention;
With adding appropriate amount of starch in the above-mentioned active component, stir, make 500 in tablet.
Embodiment 6: the preparation of drop pill
The raw material of Chinese medicine of getting selected following weight is standby through screening, purify, pulverizing:
Radix Astragali 25.5g, Radix Salviae Miltiorrhizae 20g, Rhizoma Chuanxiong 12g, Rhizoma Atractylodis 5g, Rhizoma Acori Graminei 7g, Rhizoma Coptidis 5g, Borneolum Syntheticum 0.08g;
Get the Radix Astragali, Radix Salviae Miltiorrhizae adds 9 times of water gagings, reflux, extract, 2 times, each 3 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei add 9 times of water gagings and extracted volatile oil 5 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 8 times of water gagings again and extracted 3 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 0.5g crude drug, cool, add 95% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 3g crude drug to 1ml, add 95% ethanol, making determining alcohol is 70%, after the standing over night, filter, reclaim ethanol, concentrate out cream, under 60 ℃, be concentrated into relative density 1.25～1.33; Rhizoma Coptidis adds 9 times of amount 95% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.5g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,5 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
Get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, adds mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, and it is even to change material at 80～85 ℃, makes active component of the present invention;
80 ℃ of addings in the above-mentioned active component, amount in 2.5～3.5 times of fused polyethylene glycol 6000s of total extractum amount, are stirred, move in the drop pill machine, drip system, get 1000 of drop pills at 80～85 ℃.
Embodiment 7: the preparation of drop pill
The raw material of Chinese medicine of getting selected following weight is standby through screening, purify, pulverizing:
Radix Astragali 12.5g, Radix Salviae Miltiorrhizae 8.5g, Rhizoma Chuanxiong 7.5g, Rhizoma Atractylodis 8.5g, Rhizoma Acori Graminei 8.5g, Rhizoma Coptidis 4.5g, Borneolum Syntheticum 0.05g;
Get the Radix Astragali, Radix Salviae Miltiorrhizae adds 6 times of water gagings, reflux, extract, 2 times, each 1.5 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei add 6 times of water gagings and extracted volatile oil 8 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 6 times of water gagings again and extracted 1.5 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 1g crude drug, cool, add 99% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 3g crude drug to 1ml, add 99% ethanol, making determining alcohol is 70%, after the standing over night, filter, reclaim ethanol, concentrate out cream, be concentrated into relative density 1.25～1.33 at 60 ℃; Rhizoma Coptidis adds 6 times of amount 99% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.4g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,6 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
Get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, adds mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, and it is even to change material at 60～90 ℃, makes active component of the present invention;
80 ℃ of addings in the above-mentioned active component, amount in 2.5～3.5 times of fused polyethylene glycol 6000s of total extractum amount, are stirred, move in the drop pill machine, drip system, get 1000 of drop pills at 80～85 ℃.
Claims (9)
1, a kind of medicine of controlling dementia disease is characterized in that it mainly is to be made by following materials of weight proportions medicine:
Radix Astragali 8.5-25.5 Radix Salviae Miltiorrhizae 8.5-25.5 Rhizoma Chuanxiong 5-15 Rhizoma Atractylodis 5-15
Rhizoma Acori Graminei 5-15 Rhizoma Coptidis 1.5-7.5 Borneolum Syntheticum 0.01-0.8.
2, the medicine of treatment dementia disease according to claim 1, its raw material preferred weight proportioning is:
Radix Astragali 12-20 Radix Salviae Miltiorrhizae 12-20 Rhizoma Chuanxiong 7-12 Rhizoma Atractylodis 7-12
Rhizoma Acori Graminei 7-12 Rhizoma Coptidis 2-5 Borneolum Syntheticum 0.03-0.08.
3, according to the medicine of the described treatment dementia disease of claim 2, its raw material optimum weight proportioning is:
The Radix Astragali 16.7 Radix Salviae Miltiorrhizaes 16.7 Rhizoma Chuanxiongs 10 Rhizoma Atractylodis 10 Rhizoma Acori Graminei 10 Rhizoma Coptidis 3.3 Borneolum Syntheticums 0.0667.
4, the dull-witted medicine of the described treatment of root claim 1 is characterized in that making with following drug ratio and method:
Radix Astragali 8.5-25.5 Radix Salviae Miltiorrhizae 8.5-25.5 Rhizoma Chuanxiong 5-15 Rhizoma Atractylodis 5-15
Rhizoma Acori Graminei 5-15 Rhizoma Coptidis 1.5-7.5 Borneolum Syntheticum 0.01-0.8
(1) Radix Astragali, Radix Salviae Miltiorrhizae add 6-14 times of water gaging, reflux, extract, 1-4 time, and each 0.5-3 hour, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 6-14 times of water gaging and extracted volatile oil 4-12 hour with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 6-14 times of water gaging again and extracted 0.5-3 hour, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 0.5-3g crude drug, cool, add 86-99% ethanol, making determining alcohol is 70-85%, after the standing over night, filter, reclaim ethanol and approximate the 1-5g crude drug, adding 86-99% ethanol to 1ml, making determining alcohol is 70-85%, after the standing over night, filter, reclaim ethanol, under 40-80 ℃ of condition, concentrate out cream, to relative density 1.10～1.45;
(2) Rhizoma Coptidis adds 4-12 and doubly measures the 50-95% alcohol reflux 1-4 time, and each 1-4 hour, merge extractive liquid,, filter, reclaim ethanol and be about the 0.1-0.5g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,0-8 ℃ of cold preservation is spent the night, filter, filter cake repeatedly washs with distilled water, 60-90 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
(3) get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, the 60-90 ℃ of fused polyethylene glycol 6000 that adds 1～6 times of total extractum amount, stir, add mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, it is even to change material at 60～95 ℃, promptly gets active component;
(4): this active component can add suitable adjuvant, makes tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid on the pharmaceutics, sucks agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, spray, drop pill etc.
5, the dull-witted medicine of the described treatment of root claim 4 is characterized in that making with following drugs and method:
Radix Astragali 8.5-25.5 Radix Salviae Miltiorrhizae 8.5-25.5 Rhizoma Chuanxiong 5-15 Rhizoma Atractylodis 5-15
Rhizoma Acori Graminei 5-15 Rhizoma Coptidis 1.5-7.5 Borneolum Syntheticum 0.01-0.8
(1) Radix Astragali, Radix Salviae Miltiorrhizae add 8-12 times of water gaging, reflux, extract, 1-3 time, and each 1-2 hour, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei adds 8-12 times of water gaging and extracted volatile oil 6-10 hour with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 8-12 times of water gaging again and extracted 1-2 hour, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 0.8-1.5g crude drug, cool, add 90-96% ethanol, making determining alcohol is 75-83%, after the standing over night, filter, reclaim ethanol and approximate the 2-4g crude drug, adding 90-96% ethanol to 1ml, making determining alcohol is 75-83%, after the standing over night, filter, reclaim ethanol, under 55-65 ℃ of condition, concentrate out cream, to relative density 1.20～1.35;
(2) Rhizoma Coptidis adds 6-10 and doubly measures 70-80% alcohol reflux twice, and each 1-3 hour, merge extractive liquid,, filter, reclaim ethanol and be about the 0.2-0.4g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,3-6 ℃ of cold preservation is spent the night, filter, filter cake repeatedly washs with distilled water, 75-85 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves
(3) get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, add 2.5～3.5 times of total extractum amounts, 75-85 ℃ fused polyethylene glycol 6000, stir, add mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, it is even to change material at 70～90 ℃, promptly gets active component;
(4) this active component can add suitable adjuvant, makes tablet on the pharmaceutics, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, granule, electuary, pill, powder, unguentum, suspensoid, powder, solution, ointment, plaster, drop pill etc.
6, the dull-witted medicine of the described treatment of root claim 1 is characterized in that making with following drugs and method:
Radix Astragali 8.5-25.5 Radix Salviae Miltiorrhizae 8.5-25.5 Rhizoma Chuanxiong 5-15 Rhizoma Atractylodis 5-15
Rhizoma Acori Graminei 5-15 Rhizoma Coptidis 1.5-7.5 Borneolum Syntheticum 0.01-0.8
(1) Radix Astragali, Radix Salviae Miltiorrhizae add 10 times of water gagings, reflux, extract, 2 times, and each 1.5 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei add 10 times of water gagings and extracted volatile oil 8 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 10 times of water gagings again and extracted 1.5 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 1g crude drug, cool, add 95% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 3g crude drug to 1ml, add 95% ethanol, making determining alcohol is 80%, after the standing over night, filter, reclaim ethanol, under 60 ℃ of conditions, concentrate out cream, to relative density 1.25～1.33;
(2) Rhizoma Coptidis adds 8 times of amount 75% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.3g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,5 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
(3) get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, add 2.5～3.5 times of total extractum amounts, 80 ℃ of fused polyethylene glycol 6000s, stir, add mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, it is even to change material at 80～85 ℃, promptly gets active component;
(4) this active component can add suitable adjuvant, makes tablet on the pharmaceutics, capsule, hard capsule, soft capsule, oral liquid, granule, electuary, pill, powder, unguentum, powder, solution, ointment, plaster, drop pill etc.
7, the dull-witted medicine of the described treatment of root claim 1 is characterized in that making with following drugs and method:
The Radix Astragali 16.7 Radix Salviae Miltiorrhizaes 16.7 Rhizoma Chuanxiongs 10 Rhizoma Atractylodis 10 Rhizoma Acori Graminei 10 Rhizoma Coptidis 3.3 Borneolum Syntheticums 0.0667;
(1) Radix Astragali, Radix Salviae Miltiorrhizae add 10 times of water gagings, reflux, extract, 2 times, and each 1.5 hours, extracting solution filters, and was standby; Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei add 10 times of water gagings and extracted volatile oil 8 hours with volatile oil extractor, volatile oil is standby, filtrate extract, medicinal residues add 10 times of water gagings again and extracted 1.5 hours, merge the water extract, filtration is evaporated to 1ml with the merging of milkvitch-red sage extracting solution and approximates the 1g crude drug, cool, add 95% ethanol, making determining alcohol is 60%, after the standing over night, filter, reclaim ethanol and approximate the 3g crude drug to 1ml, add 95% ethanol, making determining alcohol is 80%, after the standing over night, filter, reclaim ethanol, under 60 ℃ of conditions, concentrate out cream, to relative density 1.25～1.33;
(2) Rhizoma Coptidis adds 8 times of amount 75% alcohol reflux twice, each 2 hours, merge extractive liquid,, filter, reclaim ethanol and be about the 0.3g crude drug to 1ml, the adding concentrated hydrochloric acid is transferred PH1～2,5 ℃ of cold preservations are spent the night, filter, filter cake repeatedly washs with distilled water, 80 ℃ of oven dry, pulverize, cross 80 mesh sieves, Borneolum Syntheticum is pulverized, and crosses 80 mesh sieves;
(3) get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Acori Graminei mixed volatilization oil adding Rhizoma Coptidis extract, heating in water bath makes dissolving, add 2.5～3.5 times of total extractum amounts, 80 ℃ of fused polyethylene glycol 6000s, stir, add mixing extractum such as the Radix Astragali, and the Borneolum Syntheticum fine powder, it is even to change material at 80～85 ℃, drip system at 80-85 ℃, promptly get drop pill.
8, claim 1, the application of 2 or 3 described medicines in preparation treatment chronic dementia, senile dementia, vascular dementia, Alzheimer medicine.
9, claim 1, the application of 2 or 3 described medicines in the disturbance of consciousness medicine that preparation treatment raising learning and memory ability, chronic cerebral dysfunction syndrome, improvement cause because of cerebral thrombosis, cerebral arteriosclerosis, brain trauma, apoplexy, encephalitis.
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| CN102475781A (en) * | 2010-11-29 | 2012-05-30 | 天津天士力制药股份有限公司 | Method No.3 for preparing traditional Chinese medicine composition used for treating essential hypertension |
| CN101439135B (en) * | 2007-11-22 | 2012-07-04 | 天津天士力制药股份有限公司 | Chinese medicine granule containing extract of grassleaved sweetflag rhizome and preparation method thereof |
| CN103083558A (en) * | 2013-01-10 | 2013-05-08 | 山东凤凰制药股份有限公司 | Novel application of traditional Chinese medicine composition for treating cerebral infarction during acute stage and earlier restoration stage |
| CN103919800A (en) * | 2013-01-11 | 2014-07-16 | 南通中国科学院海洋研究所海洋科学与技术研究发展中心 | Application of dextran |
| CN107213410A (en) * | 2017-06-29 | 2017-09-29 | 合肥川迪医药技术有限公司 | A kind of prescription and preparation method for treating senile dementia |
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| CN1151811C (en) * | 2001-01-04 | 2004-06-02 | 黄兆元 | Pain-relieving notoginseng mixture |
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| CN103919800B (en) * | 2013-01-11 | 2016-03-02 | 南通中国科学院海洋研究所海洋科学与技术研究发展中心 | A kind of application of glucosan |
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| CN112402554A (en) * | 2020-10-26 | 2021-02-26 | 中国中医科学院广安门医院 | Traditional Chinese medicine composition for treating leukoencephalopathy and application thereof |
| CN113413439A (en) * | 2021-07-12 | 2021-09-21 | 中山创天生物科技有限公司 | Traditional Chinese medicine formula for treating Alzheimer's disease and preparation method of compound preparation of traditional Chinese medicine formula |
| CN113413439B (en) * | 2021-07-12 | 2022-03-29 | 中山创天生物科技有限公司 | Traditional Chinese medicine formula for treating Alzheimer's disease and preparation method of compound preparation of traditional Chinese medicine formula |
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