Summary of the invention
The invention provides a kind of Chinese medicine composition that is used to treat apoplexy and preparation method thereof; Effect with clots absorbing collateral dredging, dispelling pathogenic wind and eliminating phlegm, enrich and benefit essence and blood; Be mainly used in treatment, have good effect, the advantage that no obvious toxic-side effects etc. are good because of the apoplexy due to the wind-phlegm blood stasis numbness resistance venation.
The prescription of Chinese medicine composition of the present invention is the prescription that carries out according to the rule of treatment of treating both the principal and secondary aspects of a disease, and the side is made up of Pheretima, Eupolyphaga Seu Steleophaga, Radix Polygoni Multiflori Preparata, Caulis Spatholobi, Rhizoma Acori Graminei, Rhizoma Corydalis, Rhizoma Alismatis and Rhizoma Chuanxiong.The merit that clots absorbing collateral dredging, dispelling pathogenic wind and eliminating phlegm, enrich and benefit essence and blood are arranged.We control card and lose due to the void for the stagnant passages through which vital energy circulates of the stasis of blood, obstruction of collateral caused by windphlegm, essence and blood.Passages through which vital energy circulates is blood stasis wind-phlegm impatency, then limbs hemiplegia, crooked mouth and tongue; This venation of blood stasis wind-phlegm retardance tongue, slurred speech then, hemianesthesia; Blood stasis wind-phlegm impatency brain network, essence and blood loses void and then has a dizzy spell, hypomnesis etc.
Be monarch drug with the Pheretima in the side.Pheretima is the Scorpio body of huge earthworm animal Pheretimatschiliensis Pheretima aspergillum of section (Perrier) or Allolobophora caliginosa trapezoides Allolobophora caliginosa (Savigny) Trapezoides (Ant.Duges).Salty in the mouth is cold in nature.Return liver, spleen, urinary bladder channel.Have clearing away heat and relieving the wind syndrome, collateral dredging is relievingd asthma, the diuretic effect.The property of Pheretima is walked to scurry, can dredge the meridian passage, all blockage of meridian, blood vessels are not smooth, the unfavorable all cards of podomere, whenever commonly used it, say as Compendium of Material Medica: " cold in nature and descending, cold in nature so can separate all hot diseases, descending so can urinate by tonneau, control sufficient disease and the meridian dredging also.", " solar corona " is contained: " control apoplexy and epilepsy disease, control and pass corpse, day hot disease of row ..." modern pharmacology shows that Pheretima has thrombolytic and blood coagulation resisting function, and the effect of direct solution fibrin and indirect activation plasminogen is arranged.
With Eupolyphaga Seu Steleophaga, Radix Polygoni Multiflori Preparata and Caulis Spatholobi is ministerial drug.Eupolyphaga Seu Steleophaga is all of Corydiidae insecticide eupolyphoge sinensis Eupolyphaga sinensis Walker or the female worm of Ji eupolyphoge sinensis Steleophaga plancyi (Boleny).Salty in the mouth cold in nature is returned Liver Channel, has removing blood stasis, the effect of reunion of fractured tendons and bones.The Eupolyphaga Seu Steleophaga merit is arrogated to oneself eliminating blood stasis and inducing menstruation, and softening the hard mass disappears to simmer and amasss, and carries as " the Changsha medicine is separated ": " kindization of these article congestion ...." modern pharmacology shows that Eupolyphaga Seu Steleophaga has a significant effect to cardio-cerebrovascular, and certain blood coagulation resisting function effect for reducing fat is arranged; Radix Polygoni Multiflori Preparata is the tuber of the perennial voluble herb plant of Polygonaceae Radix Polygoni Multiflori Polygonum multiflrum Thunb..Sweet-puckery flavor, slightly warm in nature is returned the Liver and kidney warp, has enrich and benefit essence and blood, the effect of the crow palpus that reinforces the kidney.Carry as " Kaibao Bencao ": " ... only pained, beneficial vim and vigour ... obey long muscles and bones for a long time, beneficial marrow, it is not old to prolong life ...." Compendium of Material Medica carries: " and the temperature compensation liver puckeryly can be restrained vital essence for this thing temperature bitter and puckery flavor, bitter the kidney invigorating, thus the liver benefiting that can nourish blood, the controlling nocturnal emission with astringent drugs kidney tonifying, muscle reinforcing and bone strengthening, black moustache is sent out, and is tonic medicine." modern pharmacology shows, Radix Polygoni Multiflori Preparata has the control blood fat and increases and atherosclerotic effect, and has function in delaying senility.Caulis Spatholobi is a pulse family climbing shrub spatholobus suberectus Spatholobus suberectus Dunn ratan.Bitter sweet and warm, promoting the circulation of blood can be enriched blood again, relaxing muscles and tendons and activating QI and blood in the collateral, and a surname's numbness is alleviated pain, and can control lumbocrural pain, and muscles and bones is numb.Modern pharmacological research shows: Caulis Spatholobi has blood coagulation, fibrinolytic effect, suppresses heart and effect of bringing high blood pressure down and expansion blood vessel anti-platelet aggregation effect blood tonification effect.
With Rhizoma Acori Graminei, Rhizoma Corydalis and Rhizoma Alismatis is adjuvant drug.Rhizoma Acori Graminei is an Araeceae herbaceos perennial Rhizoma Acori Graminei Acorus tatarinowii Schott. rhizome, and acrid in the mouth warm in nature is bitter, and GUIXIN, stomach warp have resuscitation inducing and mind tranquilizing, the effect of removing dampness to restore normal function of the stomach.Rhizoma Acori Graminei is apt to into heart channel, and the function eliminating phlegm of having one's ideas straightened out carries as " herbal classic ": " ... happy hole, tonifying five ZANG-organs, logical nine orifices ....Clothes are made light of one's life by commiting suicide for a long time, do not forget, and do not confuse, and prolong life." Compendium of Material Medica carries: " it is dead to control the attacked by pestiferous factors soldier, the infantile convulsive seizure due to fright epilepsy ... " " Bencao Congxin ": " and arduous and temperature, fragrance and loosing, happy hole, sharp nine orifices, improve visual and auditory acuity, the sounding sound dries except that wind, by the expectorant removing food stagnancy, the alleviating distention in middle-JIAO that whets the appetite ..." modern pharmacology shows, Rhizoma Acori Graminei has the study of promotion, memory effect.And can have obvious cerebral ischemia, the anaerobic condition improved.Rhizoma Corydalis is the tuber of Papaveraceae herbaceos perennial Rhizoma Corydalis Corydalis yanhusuo W.T.Wang, and acrid in the mouth warm in nature is bitter, returns liver, spleen, heart channel, have invigorate blood circulation, circulation of qi promoting and analgesic effect.Carry as Compendium of Material Medica: " Rhizoma Corydalis, the stagnation of QI in the ability promoting the circulation of blood, stasis in the gas, so ...." modern pharmacology shows, Rhizoma Corydalis has the animal normal pressure of raising or the anoxybiotic tolerance effect of reducing pressure; And the ability dilating coronary blood vessel, coronary blood flow increasing strengthens myocardial hypoxia tolerance, improves effects such as myocardial ischemia.Rhizoma Alismatis is the tuber of the perennial limnocryptophyte Rhizoma Alismatis of Alismataceae Alisma orientalis (Sam.) Juzep..Slightly sweet flavor cold in nature is returned kidney, and urinary bladder channel has promoting diuresis to eliminate damp pathogen, the effect of purging heat.Modern study shows that Rhizoma Alismatis extract has anti thrombotic action, thus can the clump blood fat reducing, suppress many-side inhibition such as endothelial cell damage, antithrombotic or alleviate atherosclerotic generation.
With the Rhizoma Chuanxiong is messenger drug.Rhizoma Chuanxiong is the dry rhizome of umbellifer Rhizoma Chuanxiong Ligusticumaohua nxiong Hrt.Acrid in the mouth, warm in nature.Return liver, gallbladder, pericardium channel.Blood circulation promoting and blood stasis dispelling is arranged, activating QI to alleviate the depression, the merit of wind-expelling pain-stopping.Carry as " herbal classic ": " main apoplexy is gone into the brain headache, arthralgia due to cold ... " Compendium of Material Medica is carried: " the gas medicine also in the blood ... hot to loose it " " book on Chinese herbal medicine converge speech ": " the up head; following regulating menstruation water, middle relieving stagnation, gas medicine in the blood ... acrid in the mouth property sun; gas is apt to away scurry and depletion of YIN coagulates the attitude of viscous; though go into blood system, can go a wind cutting again, transfer all gas." modern pharmacological research show Rhizoma Chuanxiong to platelet aggregation, thrombosis and blood viscosity all influential to cerebral circulation cerebral ischemia have the treatment and protective effect; its active component ligustrazine has pharmacological actions such as blood circulation promoting and blood stasis dispelling, anti-platelet aggregation, expansion small artery, and ferulic acid has protective effect, antiplatelet aggregative activity, the arteriosclerosis effect of pair myocardial ischemia.
All medicines share, and play the effect of clots absorbing collateral dredging, dispelling pathogenic wind and eliminating phlegm, enrich and benefit essence and blood altogether.
Chinese medicine composition of the present invention is made up of following Chinese crude drug and weight ratio thereof:
Preferably, Chinese medicine composition of the present invention is made up of following Chinese crude drug and weight ratio thereof:
Further preferred, Chinese medicine composition of the present invention is made up of following Chinese crude drug and weight ratio thereof:
Further preferred, Chinese medicine composition of the present invention is made up of following Chinese crude drug and weight ratio thereof:
The preparation technology of Chinese medicine composition of the present invention is:
Pheretima, Rhizoma Corydalis, Rhizoma Alismatis added the 60%-80% soak with ethanol 1-3 hour, reflux, extract, 1-3 time, and each 1-3 hour, filter, merging filtrate reclaims ethanol, and concentrated solution is subsequent use; Rhizoma Acori Graminei, Rhizoma Chuanxiong were soaked 0.5-3 hour, and steam distillation extracted 2-5 hour, collected volatile oil, and the aqueous solution after distillation device is in addition collected, and medicinal residues are subsequent use; Volatile oil is used beta-cyclodextrin inclusion compound, volatile oil: beta-schardinger dextrin-: the weight ratio of water is 1: 8: 80, and 40 ℃ were stirred 2-5 hour down, and mixing speed 50~800r/min after cold preservation 6-24 hour, filters, filter cake 30-70 ℃ drying, and clathrate is subsequent use; Above-mentioned medicinal residues and all the other Caulis Spatholobis, Eupolyphaga Seu Steleophaga and Radix Polygoni Multiflori Preparata three flavors were soaked 0.5-3 hour, decocted 1-3 time, each 1-5 hour, filtered; Filtrating merges with above-mentioned aqueous solution, and being concentrated into relative density is 1.05~1.10 (60 ℃), adds ethanol and makes and contain the alcohol amount and be 50-70%, stirs; Leave standstill, filter, filtrate recycling ethanol merges with above-mentioned concentrated solution; Being concentrated into relative density is 1.10~1.15 (60 ℃), adds volatile oil clathrate compound, 6 ‰ steviosin and an amount of dextrin and soluble starch, and wherein the part by weight of dextrin and soluble starch is 2: 1; Granulate, drying is processed granule, promptly gets.
Preferably, the preparation technology of Chinese medicine composition of the present invention is:
Pheretima, Rhizoma Corydalis, Rhizoma Alismatis add 60% soak with ethanol 1 hour, the reflux, extract, secondary, and each 2 hours, filter, merging filtrate reclaims ethanol, and concentrated solution is subsequent use; Rhizoma Acori Graminei, Rhizoma Chuanxiong were soaked 0.5 hour, and steam distillation extracted 3 hours, collected volatile oil, and the aqueous solution after distillation device is in addition collected, and medicinal residues are subsequent use; Volatile oil is used beta-cyclodextrin inclusion compound, volatile oil: beta-schardinger dextrin-: the weight ratio of water is 1: 8: 80, and 40 ℃ were stirred 3 hours down, mixing speed 200~400r/min, and cold preservation filtered after 12 hours, 40 ℃ of dryings of filter cake, clathrate is subsequent use; Above-mentioned medicinal residues and all the other Caulis Spatholobis, Eupolyphaga Seu Steleophaga and Radix Polygoni Multiflori Preparata three flavors were soaked 0.5 hour, decocted secondary, each 2 hours, filtered; Filtrating merges with above-mentioned aqueous solution, and being concentrated into relative density is 1.05~1.10 (60 ℃), adds ethanol and makes that to contain the alcohol amount be 60%, stirs; Leave standstill, filter, filtrate recycling ethanol merges with above-mentioned concentrated solution; Being concentrated into relative density is 1.10~1.15 (60 ℃), adds volatile oil clathrate compound, 6 ‰ steviosin and an amount of dextrin and soluble starch, and wherein the part by weight of dextrin and soluble starch is 2: 1; Granulate, drying is processed granule, promptly gets.
Concrete embodiment
Set forth the present invention in detail through following specific embodiment, but scope of the present invention is not limited in this, conspicuous change of those of ordinary skills or modification are also contained within the scope of the invention at present.
Embodiment 1
Pheretima, Rhizoma Corydalis, Rhizoma Alismatis add 60% soak with ethanol 1 hour, the reflux, extract, secondary, and each 2 hours, filter, merging filtrate reclaims ethanol, and concentrated solution is subsequent use; Rhizoma Acori Graminei, Rhizoma Chuanxiong were soaked 0.5 hour, and steam distillation extracted 3 hours, collected volatile oil, and the aqueous solution after distillation device is in addition collected, and medicinal residues are subsequent use; Volatile oil is used beta-cyclodextrin inclusion compound, volatile oil: beta-schardinger dextrin-: the weight ratio of water is 1: 8: 80, and 40 ℃ were stirred 3 hours down, mixing speed 200~400r/min, and cold preservation filtered after 12 hours, 40 ℃ of dryings of filter cake, clathrate is subsequent use; Above-mentioned medicinal residues and all the other Caulis Spatholobis, Eupolyphaga Seu Steleophaga and Radix Polygoni Multiflori Preparata three flavors were soaked 0.5 hour, decocted secondary, each 2 hours, filtered; Filtrating merges with above-mentioned aqueous solution, and being concentrated into relative density is 1.05~1.10 (60 ℃), adds ethanol and makes that to contain the alcohol amount be 60%, stirs; Leave standstill, filter, filtrate recycling ethanol merges with above-mentioned concentrated solution; Being concentrated into relative density is 1.10~1.15 (60 ℃), adds volatile oil clathrate compound, 6 ‰ steviosin and an amount of dextrin and soluble starch, and wherein the part by weight of dextrin and soluble starch is 2: 1; Granulate, drying is processed granule 1000g, promptly gets.
Embodiment 2
Pheretima, Rhizoma Corydalis, Rhizoma Alismatis add 60% soak with ethanol 1 hour, the reflux, extract, secondary, and each 2 hours, filter, merging filtrate reclaims ethanol, and concentrated solution is subsequent use; Rhizoma Acori Graminei, Rhizoma Chuanxiong were soaked 0.5 hour, and steam distillation extracted 3 hours, collected volatile oil, and the aqueous solution after distillation device is in addition collected, and medicinal residues are subsequent use; Volatile oil is used beta-cyclodextrin inclusion compound, volatile oil: beta-schardinger dextrin-: the weight ratio of water is 1: 8: 80, and 40 ℃ were stirred 3 hours down, mixing speed 200~400r/min, and cold preservation filtered after 12 hours, 40 ℃ of dryings of filter cake, clathrate is subsequent use; Above-mentioned medicinal residues and all the other Caulis Spatholobis, Eupolyphaga Seu Steleophaga and Radix Polygoni Multiflori Preparata three flavors were soaked 0.5 hour, decocted secondary, each 2 hours, filtered; Filtrating merges with above-mentioned aqueous solution, and being concentrated into relative density is 1.05~1.10 (60 ℃), adds ethanol and makes that to contain the alcohol amount be 60%, stirs; Leave standstill, filter, filtrate recycling ethanol merges with above-mentioned concentrated solution; Being concentrated into relative density is 1.10~1.15 (60 ℃), adds volatile oil clathrate compound, 6 ‰ steviosin and an amount of dextrin and soluble starch, and wherein the part by weight of dextrin and soluble starch is 2: 1; Granulate, drying is processed granule 1000g, promptly gets.
Embodiment 3
Preparation technology is with embodiment 1
Embodiment 4
Preparation technology is with embodiment 1
Embodiment 5
Preparation technology is with embodiment 1
Embodiment 6
Preparation technology is with embodiment 1
Embodiment 7
Preparation technology is with embodiment 1
Embodiment 8
Preparation technology is with embodiment 1
Embodiment 9 medicines of the present invention are to the influence of middle cerebral artery ischemia-reperfusion rat model
1, medicine and reagent
The obtained product of embodiment of the invention 1-8 faces with preceding and is configured to desired concn with distilled water,
Nimotop (nimodipine), Bayer HealthCare Co;
2, laboratory animal
Male SD rat, 250~350g is provided by Shanghai Slac Experimental Animal Co., Ltd., ticket number: SCXK (Shanghai) 2007-0005.
3, experiment condition
Before and after the administration, cleaning level SD rat is adopted in test, and in Nanjing University of Traditional Chinese Medicine's Experimental Animal Center, sub-cage rearing is freely drunk water, 24 ± 5 ℃ of room temperatures.Laboratory animal occupancy permit number: SYXK (Soviet Union) 2007-0030.
4, statistical method
The SPSS17.0 statistical software carries out mathematical statistics.Enumeration data adopts single factor variance analysis, representes that with mean ± standard deviation
measurement data adopts rank test.
5, experimental technique and result
5.1 divide into groups and administration
Get the SD rat, be divided into 6 groups at random according to body weight, sham operated rats; Model group, positive drug group (nimodipine 32.4mg/kg), medicine high dose group of the present invention (1.371g/kg); Dose groups in the medicine of the present invention (0.457g/kg), medicine low dose group of the present invention (0.153g/kg).Gastric infusion, sham operated rats and model group give the equal-volume distilled water.The rat administration is 7 times before the modeling, and 1h carries out modeling after the last administration, gets the preceding 1h of brain and is administered once.
5.2 model preparation
(1) preparation of line bolt
Use is about 5cm, and an end of the fishing line of diameter 0.285mm is heated to be ganoid sphere, in that 20mm sentences the marking pen labelling apart from the pommel, is positioned in the normal saline subsequent use behind the alcohol disinfecting.
(2) cerebral ischemic reperfusion in rats model
1h carries out modeling after the last administration; Rat is with 10% chloral hydrate (350mg/kg) intraperitoneal anesthesia; Lie on the back after the anesthesia on operating-table, cut, separate right carotid, external carotid artery, internal carotid artery from the neck main track; Prick the external carotid artery distal end with No. 0 toe-in, and separate the outer branch of the cranium pterygoid process arteria palatina of internal carotid artery.Close common carotid artery, internal carotid artery with the vascular clamp folder, ready line bolt is inserted from external carotid artery, go into cranium through internal carotid artery through common carotid artery Y shape crotch; The blocking-up middle cerebral artery; Line bolt insertion depth is about 20mm, ligation external carotid artery proximal part, observe no hemorrhage after; Sew up wound, and the line bolt used when pouring in the about 1.5cm length of external reservation again.External cable bolt when pouring into is again got back in the internal carotid artery its pommel, can recover the blood supply of middle cerebral artery.In ischemia 4h, irritate back 20h again and carry out behavioristics's scoring.
5.3 observation index
5.3.1 behavioristics's scoring
Observe the rat behavior of postoperative 4h, 24h, and it is marked, methods of marking is following:
(1) it is unsettled with it to mention the mouse tail, observes rat forelimb performance, receives inward turning person in left fore has, and is chosen as 4 fens, otherwise 0.(2) with the sliding place of mouse horizontalization, push away the both sides shoulder respectively to side shifting, check the resistance of opposing, normal rat bilateral resistance piles.When right shoulder moves to the left, find the resistance descender,, be divided into 1~3 fen according to the difference of resistance decline degree (light, in, heavy).(3) place Mus box wire netting to cover the mouse forelimb, observe the muscular tension of forelimb.Normal rat two muscle of anterior limb tension force symmetry.Find the obvious descender of left fore muscular tension,, be divided into 1~3 fen according to the weight of muscle tone decline degree.Comprehensive above scoring, full marks are 10 minutes, wherein, integrate score is included experimental group in and is added up greater than (equaling) 5 fens persons.The high more person of score explains that then its behavior disorder is serious more.
5.3.2 infarct size is calculated
Modeling is the sacrificed by decapitation rat after 24 hours, gets brain, and brain is positioned over 10min in about 2~3 ℃ of normal saline, and behind removal olfactory bulb, XIAONAO and the low brain stem, crown 5 cuttves of cutting are cut into 6, every thick about 2mm.Rapidly the brain sheet is put in the phosphate buffer solution that 5ml contains 1%TTC then, the lucifuge temperature is incubated 30min, and 7-8min stirs once at interval.After dyed, normal cerebral tissue should be rose, and ischemic tissue then is a white, and boundary is clearly demarcated.After the TTC dyeing brain tissue slice being tiled in the blue background plate takes pictures.With Image-pro blus6.0 image analysis software, calculate full brain area, ischemic region area, and calculate the cerebral infarction rate according to following formula:
Cerebral infarction rate=ischemic region area/full brain area * 100%
5.3.3 the mensuration of brain water content and cerebral index
24 hours sacrificed by decapitation rats are got brain behind the ischemia-reperfusion, put dry to constant weight, and the slide of having weighed on claim weight in wet base after; Put 24h in 105 ℃ of baking ovens, dry, claim its gross weight to constant weight; Its gross weight is deducted slide heavily is the brain dry weight, by formula calculate cerebral index and brain water content:
Heavy (the g)/body weight (g) * 100% of cerebral index=cutaneous horn
Brain water content (%)=heavy (g) * 100% of [heavy (g) brain stem of cutaneous horn heavy (g)]/cutaneous horn
5.3.4 blood parameters
Behind the laboratory animal ischemia 24h, with 10% chloral hydrate (350mg/kg) intraperitoneal anesthesia, dorsal position is fixed; Get blood 4.5ml through right carotid artery, room temperature leaves standstill half an hour, the centrifugal 15min of 2500r/min; Separation of serum, the content of SOD, MDA, N0, ATP and LDH in the detection serum.
5.4 experimental result
(1) experimental result is as shown in table 1, and model group laboratory animal 4h and the scoring of 24h behavioristics raise more obvious, relatively have significant difference (P<0.01) with sham operated rats; Embodiment of the invention 1-8 makes the drug administration group and model group compares, 4h behavioristics scoring there was no significant difference (P>0.05).After pouring into 20h again, positive drug group and the scoring of high dose group Animal Behavior Science reduce, and relatively have significant difference (P<0.05) with model group.
Table 1 medicine of the present invention is to the influence
of cerebral ischemia re-pouring rat (MCAO) behavioristics and brain death rate
Compare ##P<0.01 with sham operated rats; Compare * P<0.05, * * P<0.01 with model group.
(2) experimentation is found, model group cerebral index, brain water content and infraction rate raise comparatively obvious, relatively have significant difference (P<0.05, P<0.01) with sham operated rats.Positive drug group, embodiment of the invention 1-8 make cerebral infarction rate and the cerebral index that the middle and high dose groups of medicine can obviously reduce rat MCAO postoperative, relatively have significant difference (P<0.05, P<0.01) with model group.Each administration group brain water content also decreases, but compares there was no significant difference (P>0.05) with model group.The result sees table 2.
Table 2 medicine of the present invention is to the influence
of ischemia-reperfusion rat (MCAO) infraction rate, cerebral index and brain water content
Compare ##P<0.01 with sham operated rats; Compare * P<0.05, * * P<0.01 with model group.
6, conclusion
Behind the drug administration of the present invention, the behavioristics that middle and high dose groups can obviously reduce middle cerebral artery ischemia-reperfusion injury model rat divides equally; The obvious increased SOD vigor of high dose group, NO content, LDH vigor and ATP content; Rise also influential to brain water content and MDA.Above result shows that medicine of the present invention has protective effect to the brain injury of middle cerebral artery ischemia-reperfusion injury model rat; Brain energy metabolism impairment to animal pattern has the improvement effect.