CN1179741C - Compound Chinese medicine for treating cerebrovascular disease - Google Patents
Compound Chinese medicine for treating cerebrovascular disease Download PDFInfo
- Publication number
- CN1179741C CN1179741C CNB021186235A CN02118623A CN1179741C CN 1179741 C CN1179741 C CN 1179741C CN B021186235 A CNB021186235 A CN B021186235A CN 02118623 A CN02118623 A CN 02118623A CN 1179741 C CN1179741 C CN 1179741C
- Authority
- CN
- China
- Prior art keywords
- brain
- cerebral
- chinese medicine
- radix
- ischemia
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to a Chinese medicine composition for treating and preventing acute cerebral ischemia, cerebral anoxia, cerebral hemorrhage, chronic brain injuries and sequelae thereof after operations of brain contusion and brain trauma hematoma and brain diseases, such as senile dementia, etc., namely a compound Chinese medicine 9802. The compound Chinese medicine 9802 of the present invention can particularly relieve tardive brain injuries of global brain ischemia. The compound Chinese medicine 9802 comprises ingredients, such as baical skullcap root, chuanxiong, angelica, red peony root, cortex moutan, safflower, peach seed, astragalus root, liquoric root, etc. Proved by animal experiments, the compound Chinese medicine 9802 of the present invention can prevent the degeneration of tardive neurons and vascular endothelial cells, such as thrombosis and infarction, in the brain after cerebral ischemia and prevent the degeneration and slow extinction of the neurons; besides, the compound Chinese medicine 9802 can reduce amyloid protein deposits in the brain and alleviate and prevent hippocampal gyrus atrophy and fibrosis.
Description
Invention field
The present invention relates to a kind of be used for the treatment of with prophylaxis of acute cerebral ischemia, cerebral anoxia, cerebral hemorrhage, cerebral anoxia and brain contusion after chronic injury and sequela thereof, the Chinese medicine composition of disease of brain such as senile dementia, promptly herbal mixture 9802.Medicine of the present invention especially can be used for alleviating delayed cerebral injury after the global brain ischemia.
Background technology
Acute cerebrovascular disease is commonly called as apoplexy or " apoplexy ", is all very high serious disease of sickness rate, disability rate, mortality rate, good sends out in more than 50 years old, elderly population.It is the reason that causes most of adult maimed persons, and accounts for the 3rd or the 4th of the cause of death.Apoplexy is divided two kinds of ischemic and hemorrhagic.Ischemic Stroke often is called acute cerebral ischemia, and dividing local ischemia again is two kinds of cerebral infarction and global brain ischemia.Global brain ischemia sees heart attack, operation on heart, shock, though it does not cause paralysis, symptom also is very serious, as serious Mental retardation, plant man etc.In addition, cerebral ischemic injury also sees cerebral hemorrhage and patient with brain trauma, large stretch of ischemia injury focus be centered around hemorrhagic focus and dampen the position around.Cerebral ischemia means cerebral tissue deficiency of oxigen and glucose supply simultaneously.Anoxia is to cause the main cause of damage.The reason that causes cerebral anoxia is a lot, in the small towns and the rural area of NORTH CHINA, because the heating system imperfection often has the situation of carbon monoxide poisoning to take place.Cerebral anoxia is the important and main mechanism of carbon monoxide poisoning.When cerebral anoxia was serious, stupor appearred in patient.Tardy encephalopathy (HIE) often takes place in the patient who occurs stupor during poisoning afterwards.Poisoning patient can have two, three all asymptomatic stages after being revived from stupor by first aid, suddenly occur dysnoesia, low grade fever or moderate heating, orthocolosis or spastic paralysis then and show parkinson, the state of an illness reached the peak and serious dementia is arranged in the morbidity back in six to eight weeks.It is between twenty and fifty that patient mostly is, though not deadly can stay serious sequela, disablement can not be lived on one's own life.Unfortunately, the research of past over 40 years does not find that effective Therapeutic Method saves the acute injury after cerebral tissue avoids cerebral ischemia and cerebral anoxia, let alone treats its chronic injury.Therefore, it is very important not only to treat cerebral ischemia, and chronic injury takes place just to seem even more important behind prevention of brain ischemia and the cerebral anoxia.
Senile dementia claims that again Alzheimer (Alzheimer ' s Disease) is another serious disease in the elderly population, and is becoming serious social problem.The reason of this disease it be unclear that.Cause that two dull-witted big diseases first are the Alzheimer diseases, the secondth, cerebrovascular.Recently, scientists is suspected cerebrovascular, and special cerebral ischemia may be relevant with the pathogenesis of senile dementia.At present, confirmed that cerebral trauma causes the Alzheimer disease.Cerebral trauma causes deposition and obvious brain atrophy in a large amount of amyloid brains.Amyloid makes those neuron death that contacts with it.
That more troubling is is that slowly occur after acute cerebral ischemia or the anoxia, that have long one period, be the Secondary cases chronic brain injury of feature with new cerebral infarction and the neuron regression that extensively is dispersed in, this is a research field that occurs recently on neuroscience (Neuroscience).
The inventor with carbon monoxide poisoning after tardy encephalopathy (HIE) be basis, the damage of tardy property is also arranged after the reasoning cerebral ischemia probably, therefore carried out series of studies, confirmed that at this ten minutes of short duration global brain ischemia can bring out the tardy brain injury second time with zoopery recently.This damage comes across four to ten weeks behind the primary injury.The brain secondary injury comprises that striatum and hippocampal gyrus not exclusively block, and its range size does not wait, and comprises large-scale focus and little infraction.Meanwhile, be also shown in tangible vascular endothelial cell regression, thrombosis, and circumvascular neuron regression of regression and disappearance.This brain secondary lesion not only begins on the time of occurrence at fervescence and pathological changes, and consistent with tardy encephalopathy after the carbon monoxide poisoning in the pathological change.The more important thing is that this tardy secondary injury is more serious than the acute stage damage.In addition, active amyloid and precursor protein thereof deposition also occurs in brain in the Alzheimer disease, deposition concentrates on the bottom of brain, with more to distribute around the venule especially around the blood vessel, exists surplus and Yu Bazhou of ten weeks to reach peak [consulting document 1-3].Like this, thereby the inventor has used the time in 6 years to confirm tardy property secondary injury can occur behind acute cerebral ischemia and cerebral anoxia, the time that begins to occur is behind the primary injury three, all around and may extend to more than ten weeks, its damage character is two big classes: 1, the vascular endothelial cell degeneration is damaged the cerebral infarction of following thrombosis, thromboembolism and differing in size, and former regression of blood vessel peripheral nerve and disappearance; 2, deposition in the amyloid brain.
Because 40 years in the past studies confirm that can not be saved acute stage neuron death after the cerebral ischemia, and this secondary injury is more serious than primary injury usually, therefore, prevent this for the second time brain injury be extremely important.We think that the key of prevention of brain secondary injury is to avoid the vascular endothelial cell regression, and then prevent thrombosis and avoid blood-brain barrier disruption, finally prevent cerebral infarction and the former extinction of blood vessel peripheral nerve.
Be surprisingly found out that now by providing according to herbal mixture of the present invention, making to address the above problem becomes possibility.The inventor has designed this research, and the people is divided into administration group, non-administration group and matched group for causing the brain tissue of rat ischemia model, the decoction that oral these medicines of administration group rat are made, and medication is identical with the method for giving patient.Check the Mus brain then, observe its pathological change, improve with pathological change and judge curative effect as standard.Found that medicine of the present invention can prevention of brain ischemia hindbrain in tardy property neuron and vascular endothelial cell regression comprise thrombosis and infraction, and neuron regression and slowly withering away.Can also reduce amyloid beta deposition in the brain, also can alleviate and atrophy of prevention of brain hippocampal gyrus and fibrosis.Thereby finished the present invention.
Summary of the invention
Medicine of the present invention comprises following raw material by weight:
Radix Scutellariae 0.1-10 Rhizoma Chuanxiong 0.1-10 Radix Angelicae Sinensis 0.1-10
Radix Paeoniae Rubra 0.1-10 Cortex Moutan 0.1-10 Flos Carthami 0.1-10
Semen Persicae 0.1-10 Radix Astragali 0.1-10 Radix Glycyrrhizae 0.1-10
The preferred weight ratio range of medicine of the present invention is:
Radix Scutellariae 0.5-3 Rhizoma Chuanxiong 0.5-3 Radix Angelicae Sinensis 0.5-3
Radix Paeoniae Rubra 0.5-3 Cortex Moutan 0.5-3 Flos Carthami 0.5-3
Semen Persicae 0.5-3 Radix Astragali 0.5-3 Radix Glycyrrhizae 0.2-1
The most preferably weight proportion scope of medicine of the present invention is:
Radix Scutellariae 1-2 Rhizoma Chuanxiong 1-2 Radix Angelicae Sinensis 1-2
Radix Paeoniae Rubra 1-2 Cortex Moutan 1-2 Flos Carthami 1-2
Semen Persicae 1-2 Radix Astragali 1-2 Radix Glycyrrhizae 0.3-0.7
Medicine of the present invention can also contain optional member, pharmaceutical auxiliary agent for example, and other simply or kinds of traditional Chinese medicines raw material (for example Rhizoma Zingiberis Recens 0-6, or Ramulus Cinnamomi 0-6 etc.) perhaps can make the Chinese medicine and western medicine compound preparation with Western medicine.
Can medicine of the present invention be made any dosage form that is suitable for clinical use according to the conventional method of this area, oral medicine preparation for example, tablet, capsule, powder, pill, concentrated pill etc.Liquid preparation is easy to absorb.In view of patient's state of consciousness, liquid preparation is easy to take most, therefore preferably uses with oral liquid.The oral safety non-toxic of Radix Scutellariae absorbs fast, and is poisonous during intravenous injection, so injection is not preferred.
Press modern medicine study, Radix Scutellariae is a powerful antioxidant in the side.It suppresses, reduces the formation of oxygen-derived free radicals, and can remove oxygen-derived free radicals, increases the cell DNA repair ability, and the protection cell membrane reduces cell death [consulting document 6-9].Radix Scutellariae suppresses prostaglandin such as PGD
2And PGE
2Form, so Radix Scutellariae can be eliminated vasospasm and pre-preventing thrombosis [consulting document 10-12].Rhizoma Chuanxiong, Flos Carthami and Semen Persicae prevent platelet aggregation and reduce biologically active pdgf, thereby protection vascular endothelial cell [consulting document 13], reduce amyloid and form [consulting document 14,15].Radix Scutellariae, Rhizoma Chuanxiong, Flos Carthami, Semen Persicae and Radix Angelicae Sinensis reduce thromboxane and form, thus the thrombosis of preventing.Radix Angelicae Sinensis reduces the 5-HT secretion, prevents vasoconstriction.Radix Paeoniae Rubra and Cortex Moutan prevention fibrosis.The Radix Astragali and Radix Glycyrrhizae are strengthened the DNA damage reparation.Radix Scutellariae, Radix Paeoniae Rubra and Cortex Moutan, the Radix Astragali can also diminish inflammation.The Flos Carthami and the Radix Astragali also are antioxidants.After cerebral blood supply recovers, because the supply again of oxygen thereby produce a large amount of oxonium ions of crossing, cause undesired lipid metabolism on the cell membrane (comprising vascular endothelial cell and neuron) by these oxygen-derived free radicals again, and then cause cell membrane damage, last cell death.Injured thromboxane generation, the platelet of then causing of vascular endothelial cell assembled, and leukocyte adheres to and final formation thrombosis.There are several weeks in injured its regression of back of endotheliocyte.Cerebral ischemia comes down to an inflammatory process.This nine flavors medicine forms the Comprehensive Treatment effect jointly: reduce that oxygen-derived free radicals, protection cell membrane help injury repairing, prevent thrombosis, [consulting document 13] reduces inflammation; just in time solve the Several Key Problems in the damage process after the cerebral ischemia, and meet the promoting flow of QI and blood of Chinese medicine, the theory of eliminating blood stasis to promote regeneration of blood.It may be owing to reduce biologically active pdgf this albumen generation to be reduced that this Chinese medicine reduces one of mechanism of amyloid beta deposition in the brain; two of mechanism is this medicine protection vascular endothelial cells; and then keep normal blood brain barrier, prevent that paraprotein from entering the cause of brain essence [consulting document 14,15].
Indication:
1, acute stage after the cerebral ischemia, subacute stage, chronic phase.
2, acute stage behind the cerebral anoxia, subacute stage, chronic phase.
3, acute stage behind the cerebral hemorrhage, subacute stage, chronic phase.Cerebral hemorrhage morbidity bring into use after seven days or hematoma clearance after bring into use after seven days, to avoid again hemorrhage.
4, after the brain contusion and after the operation of cerebral trauma cephalophyma, acute stage and subacute stage, chronic phase.Falling ill back seven days or performing the operation began to take in back seven days, to avoid hemorrhage again.
5, to the possible people of global brain ischemia and cerebral thrombosis is arranged, available medicine is as prophylactic.
6, leukoencephalopathy around the dispersivity cerebral malacia that cerebrovascular and cerebral trauma caused and the ventricles of the brain.
7, carbon monoxide poisoning stupor and tardy encephalopathy (HIE) thereof
8, senile dementia
9, acute myocardial infarction is in order to protect cardiac muscle, prevention myocardial fibrosis and cicatrization.
10, hepatitis is in order to the prevention liver cirrhosis.
Drug dose, the course of treatment and using method:
Using method: oral is good
The course of treatment: February
Effective dose: 0.1-0.3g/kg body weight/day, but Radix Glycyrrhizae 0.03-0.1g/kg body weight/day.
Optimal dose: 0.2g/kg body weight/day, Radix Glycyrrhizae 0.07g/kg body weight/day
Adult's dosage: except that Radix Astragali 12g/ day, Radix Glycyrrhizae 3g/ day, all the other are 10g/ day.
Child dose: by above-mentioned Rapid Dose Calculation.
The points for attention of taking medicine: this medicine does not have obviously and serious side effects.Have the stomach discomfort sense, if any this phenomenon, can be used as medicine or clothes in addition with Rhizoma Zingiberis Recens 6 gram, it is edible that also available boiling water reconstitutes Amylum Nelumbinis Rhizomatis 30-50 gram, once a day.
Old body deficiency and coldness person added with Ramulus Cinnamomi 3-6 gram/day, (drugs) to be decocted and taken as a drink.
Contraindication:
Bleeding tendency person's forbidding is arranged.The gravid woman avoids usefulness.
Description of drawings
Fig. 1 is different body temperature comparison diagrams behind treatment group, matched group and the non-administration group rat ischemia.
Fig. 2 is the counting diagram of neuron regression behind treatment group, matched group and the non-administration group rat whole brain ischemia.
Fig. 3 is an amyloid beta deposition point counting diagram in brain during 8 weekends after treatment group, matched group and the non-administration group global brain ischemia.
Fig. 4 uses H ﹠amp; The painted brain tissue slice mirror of E figure below has shown the neuron regression in non-administration group rat brain.
Fig. 5 is the brain tissue slice mirror figure below with anti-EBA labelling normal blood vessels endotheliocyte.
Fig. 6 is with the painted brain tissue slice mirror of NCL-beta-Amyloid figure below, has shown amyloid beta deposition in the brain.
Fig. 7 is tissue slice mirror figure below of first section (CA1) injury repairing of hippocampal gyrus after the global brain ischemia.Fig. 8 is tissue slice mirror figure below of interior neuron of non-treatment group rat brain and vascular endothelial cell damage.
Embodiment
Below in conjunction with embodiment the present invention is described, it should be understood that these embodiment only are used to purpose of the present invention is described, rather than limit the scope of the invention.
Radix Scutellariae 12g Rhizoma Chuanxiong 12g Radix Angelicae Sinensis 12g
Radix Paeoniae Rubra 12g Cortex Moutan 12g Flos Carthami 12g
Semen Persicae 12g Radix Astragali 12g Radix Glycyrrhizae 3g
Above-mentioned raw materials is decocted with water, make oral medicine.
Embodiment 2
Radix Scutellariae 12g Rhizoma Chuanxiong 12g Radix Angelicae Sinensis 12g
Radix Paeoniae Rubra 12g Cortex Moutan 12g Flos Carthami 12g
Semen Persicae 12g Radix Astragali 12g Radix Glycyrrhizae 3g
Ramulus Cinnamomi 5g
Above-mentioned raw materials is decocted with water, make oral medicine.
Radix Scutellariae 12g Rhizoma Chuanxiong 12g Radix Angelicae Sinensis 12g
Radix Paeoniae Rubra 12g Cortex Moutan 12g Flos Carthami 9g
Semen Persicae 12g Radix Astragali 12g Radix Glycyrrhizae 3g
Rhizoma Zingiberis Recens 6g Ramulus Cinnamomi 3g
Above-mentioned raw materials is decocted with water, make oral medicine.
Experiment: medicine of the present invention to global brain ischemia after the treatment and the preventive effect of tardy property secondary brain injury
After one night of Thirty male rat (body weight 265-390g) fasting with two common carotid artery ligation+body hypotension method (40-50 mmHg) at 3% halothane (halothane)+70%NO+30%O
2Undergo surgery and make 12.5 minutes (12 minutes half) global brain ischemia under the anesthesia.
The operation process: double inguinal groove district and cervical region veutro are shaved hair, a kerf is respectively cut lightly with scalpel in the sterilization back, softly and carefully peel off local soft tissue, nerve is separated with blood vessel, go a bifilar tremulous pulse and a side femoral vein vascular catheterization then, so that administration, monitoring blood pressure, vim and vigour and blood glucose and when inducing ischemia, extract a large amount of arterial bloods out and cause hypotension; Center on two carotid artery respectively with the thin plastic ties of 20cm (polyethylene PE-10), in order that the two ends of this rope are inserted in two holes of a little silicone rubber tube (Silastic tubing) that has two apertures respectively and pass this hole, then with linear system together with the two ends of rope; Carry out tracheal intubation and be connected artificial respirator, pancuronium bromide (Pavulon) i.v (0.75mg/kg) causes temporary muscular flaccidity paralysis, and reduces halothane concentration to 0.5%; The probe of two temperature monitors inserts respectively under the temporalis of left side is close to skull and anus (entering anus 5-6cm), and two warming lamps are positioned over the top of Mus head and health respectively, to make head temperature, anus temperature control at claimed range; Wait for 45 minutes and allow the interior halothane of animal body get rid of, make cerebral ischemia then.
Make ischemia: the syringe that blood suction heparin was washed at first, when treating that blood pressure is reduced to 50mmHg, will close on carotid little plastic tube with vascular forceps and push carotid artery to along plastic ties, carotid artery was tightly tied 12.5 minutes.Then, will be unclamped by the carotid artery of ligation, and the syringe inner blood will be annotated back in the femoral artery, and make blood pressure go back up to 100-120mmHg, give in the protamine and the heparin anti-coagulating effect.During off-test, the intubate in all blood vessels is all carefully taken out, and with these vascular ligations firmly in case hemorrhage, after the sterilization with wound suture.After treating that autonomous respiration recovers, animal is put back in the cage, and a cage one Mus is freely movable and obtain food and water.Control animals received either operation, but not manufactured cerebral ischemia.
Before the ischemia, in and behind the ischemia 1 hour, animal anus temperature remains in 37-37.5 ℃, temperature and remains on 36-36.5 ℃.Before and after the ischemia, arteriotony and blood glucose are all normal, arterial blood pCO
2And pO
2All be adjusted to normal range.All animals of participating in the experiment were allowed to survive 8 weeks, and at 9 o'clock in morning every day, per anum was surveyed body temperature.Last 1 day of the 8th week, under halothane anesthesia, with normal saline 2 minutes, FAM (40% formalin, glacial acetic acid, methanol, by volume 1: 1: 8 mixed liquid) carried out the brain perfusion in 19 minutes through left ventricle, ascending aorta.Perfusion pressure 100-120mmHg.Downcut the Mus head, it is immersed in a night in the FAM, then brain is taken out, brain was immersed in the FAM 1 day.By the interval of 250 μ m (micron), capsules of brain is cut into sections, again with paraffin embedding be cut into 10 microns slabs.Several adjoining sections are respectively with h and E (H ﹠amp; E), NCL-beta-Amyloid (6F/3D) (Vector Lab, Burlingame, CA, U.S.A), GFAP (DakoCorp., Calif, U.S.A) and Anti-EBA (SMI 71, Stemberger Monoclonals, Lutherville, MD, U.S.A.) dyeing.
H ﹠amp; E dyeing is in order to show neuronal injury, and NCL-beta-Amyloid detects deposition in amyloid (A-beta) brain, and GFAP indicates astrocyte abnormal and that be activated, Anti-EBA labelling normal blood vessels endotheliocyte.At last, count at microscopically.Add with Computerized analysis system (ImagingResearch, Inc., St.Catherines, Ontario Canada) measures the quantity of normal blood vessels endotheliocyte and calculated [consulting document 3-5].
Handle:
Nine kinds of Chinese herbal medicine (0.2g/kg body weight/day, but Radix Glycyrrhizae 0.07g/kg body weight/day) are put into water together and were soaked four hours, are placed on then and boil in the marmite that boils Chinese medicine 30-45 minute, make decoction and drink to Mus.Non-treatment group and control animals received either equivalent drinking-water.Treatment group (HC), non-treatment group (DW) and matched group (sham) respectively have 5 Mus.The treatment time started: behind the ischemia 4 hours.The course of treatment: 6 weeks.
Statistical procedures:
Data computer Excel software statistics, enumeration data mean ± standard deviation (x ± s) expression.Significance test ANOVA, Single Factor analyzes, and p＜0.05 is regarded as significant difference.
The result:
1, non-treatment treated animal body temperature raise since the 4th weekend, up to 38.5-39 ℃.Heating continued for 2 weeks but without infection, does not also have other unusually as seen.This heating phenomenon now looks like similar to the heating that the tardy encephalopathy (HIE) people of carbon monoxide poisoning is had.The pathologic fever is because PGE
2Acute stage roll up in damage, stimulate that thermotaxic centre causes fervescence in the hypothalamus.On the contrary, do not see treatment treated animal fervescence this moment, this meaning treatment by Chinese herbs suppresses PGE
2Generate, secondary indication does not have new damage at this moment and (Fig. 1) occur.
2, non-treatment group shows nerve regression: H﹠amp; There is more peony neuron (DN) in the non-treatment group Mus ectocinerea of E dyeing demonstration.The cell space contraction distortion of these cells, karyon are shunk and chromatin dyeing is obviously deepened.
Cerebral cortex DN counting: matched group: 11 ± 6; DW group: 190 ± 64; The HC group: 24 ± 13 (mean ± SE).
[this be DN on 3 planes of cerebral cortex, promptly behind the bregma-0.2,3.3,4.8mm, on summation]
With the matched group ratio, the treatment group is not seen the neuron regression, but not the treatment group has remarkable regression.With treatment group ratio, non-treatment group has obvious neuron regression (p＜0.05), and this phenomenon also sees thalamus and midbrain.(table 1, Fig. 2, Fig. 4)
3, treatment treated animal hippocampal gyrus CA3 place neuron is protected.Compare with matched group, non-treatment treated animal neuron herein reduces by 20% (p＜0.01).
The normal neuron counting of CA3: matched group 212 ± 17;
DW group 165 ± 25;
HC group 203 ± 33 (mean ± SD).
4, non-treatment treated animal cerebral cortex bottom (AIP and Pir district, behind the bregma-3.3mm level) normal blood vessels reduces, and the treatment treated animal does not have this existing picture herein.
In the matched group, the normal blood vessels endotheliocyte is 3% ± 0.5% of a cerebral tissue in AIP district area occupied, is 2.2% ± 0.3% in the Pir district.
The normal blood vessels endotheliocyte area occupied of cerebral ischemia rat cerebral cortex bottom:
AIP district: DW group 2 ± 0.6%; HC organizes 3% ± 0.6% (p=0.028);
Pir district: DW group 0.9% ± 0.4%; HC organizes 1.9% ± 0.4% (p=0.005) (table 2).
The damage of DW treated animal cerebral blood vessel is (table 2, Fig. 5,8) obviously, and the vascular endothelial cell regression is not obvious in treatment group (HC) animal.(table 2, Fig. 5,8)
5, (beta-amyloid protein A-beta) deposits the interior a large amount of amyloids of non-treatment treated animal cerebral cortex, and the A-beta deposition of treatment treated animal obviously is less than non-treatment group.
Add up 6 standard regions (bilateral Pir district, top 2 districts, frontal lobe add lobulus paracentralis, behind the bregma-the 3.3mm level) A-beta deposition count and find that the DW group is 661 ± 75, and the HC group is 281 ± 102, (mean ± SE) (p=0.018).Amyloid point-like deposition is concentrated with cerebral cortex bottom (AIP and Pir) and is in the majority.At hypothalamus, also can see similar variation.(table 3, Fig. 3,6)
6, two brain coxopodite districts show large stretch of infraction in the non-treatment group, and five Mus all have the little infraction of hippocampal gyrus CA1, in five Mus four have only in or severe hippocampal gyrus fibrosis and atrophy.Treatment group Mus brain is not seen focus of infarct, does not see the hippocampal gyrus atrophy yet.Have only two degree of taking a favourable turn hippocampal gyrus fibrosiss in five Mus.(Fig. 7,8)
Regression neuron quantity is relatively in the brain during 8 weekends behind the table 13 group rat cerebral ischemia
| Matched group (Sham) 5 | Treatment group (HC) 5 | Non-treatment group (DW) 5 | |
| Cerebral cortex (Cortex) | 11±5 | 24±13 | 190±64 * |
| Thalamus (Thalamus) | 1±1 | 3±2 | 49±24 * |
| Midbrain (Midbrain) | 1±1 | 6±3 | 50±20 * |
Mean ± SE,
*Compare P＜0.05 (ANOVA, Single test) with the treatment group
3 groups of rat cerebral cortex bottoms of table 2 (AIP and Pir) district's shared cerebral tissue of normal blood vessels endotheliocyte (%) amount relatively
| Matched group (Sham) 5 | Treatment group (HC) 5 | Non-treatment group (DW) 5 | |
| The AIP district | 3％±0.5％ | 3％±0.6％ | 2％±0.6％ * |
| The Pir district | 2.2％±0.3％ | 1.9％±0.4％ | 0.9％±0.4％ * |
Mean ± SD,
*Compare P＜0.05 (ANOVA, Single test) with the treatment group
The interior amyloid beta deposition speckle number of 8 all metepencephalons relatively behind 3 groups of rat cerebral ischemias of table 3
| Matched group (Sham) 5 | Treatment group (HC) 5 | Non-treatment group (DW) 5 | |
| Cerebral cortex (Cortex) | 89±49 | 281±102 | 661±75 * |
| Hypothalamus (Hypothalamus) | 8±5 | 45±20 | 150±13 * |
Mean ± SE,
*Compare P＜0.05 (ANOVA, Single test) with the treatment group
Figure: 4 (A-H), 5 (A-F), 6 (A-H), 7 (A-F), 8 (A-F)
(Dark Neuron, DN): (A, B), DW organizes (C-H) to the HC group to regression neuron in Fig. 4 brain.A-C, cerebral cortex; D, midbrain; E, thalamus; F, all regression neurons (DN) of hypothalamus place blood vessel; DN in the G, black substance; H sees small pieces neuron regression zone in the thalamus.Non-treatment group has obvious neuron regression, and treatment group (HC) is not seen the neuron regression.x800
Normal blood vessels is in Pir district: A-B, matched group in Fig. 5 brain; C-D, non-treatment group (DW); E-F, treatment group (HC).HC group blood vessel is normal, and the DW group sees that normal blood vessels obviously reduces.
A，C，E，x200；B，D，F，x800
Amyloid beta deposition: A in Fig. 6 brain, C, E-H, DW group; B, D, HC group.A β deposition is obviously organized more than HC in the DW group brain.A，B，x100；C，D，x200；E-H，x800
First section (CA1) injury repairing: A of hippocampal gyrus after Fig. 7 global brain ischemia, C, E, DW group; B, D, F, HC group.During 8 weekends, the DW group is seen the little infraction in CA1 place (A), and neuron regression (DN) (C) reaches obvious fibroplasia (E); But the HC group is not seen above-mentioned phenomenon.x800
Neuron and vascular endothelial cell damage: A in the non-treatment group of Fig. 8 rat brain, large stretch of not exclusively focus of infarct in the stricture of vagina shape; B, the former disappearance of blood vessel peripheral nerve, and form spongiform change; C, the former disappearance of blood vessel peripheral nerve, the degeneration of this blood vessel; D, the terminal expansion of little blood vessel also contains embolus; E, thrombosis in the small artery of cerebral hemisphere surface; Small artery thickens in the F, striatum, and contains leukocyte, and this circumvascular neuron obviously reduces.Above-mentioned all phenomenons see 8 weeks after the cerebral ischemia of non-treatment group, but do not see the treatment group.A，x50；B，x100；C，D，F，x 800；E，x400
Conclusion and evaluation:
This natural herbal mixture, 9802, comprise nine kinds of Chinese medicines, can prevention of brain ischemia hindbrain in neuron and vascular endothelial cell regression comprise thrombosis and infraction, and neuron regression and slowly withering away.This treatment by Chinese herbs can also reduce amyloid beta deposition in the brain, also can alleviate and atrophy of prevention of brain hippocampal gyrus and fibrosis, and inference thus allly contains brain disorder and other organ illness that ischemia injury changes and all can benefit from this medicine.
Above the present invention has been described after, those of ordinary skill in the art will be appreciated that, can make some variations and modification under the situation that does not depart from spirit and scope of the invention, they all will be included in the scope of the present invention.
List of references:
1.Lin B et al(1998)Acta Neuropathol 95：511-523。
2.Lin B et al(1999)Acta Neuropathol 97：359-368。
3.Lin B，Ginsberg MD.(2000)Pharmacology of Cerebral Ischemia 2000，pp 37-52。
4.Lin B，Ginsberg MD.(2000)Brain Res 865：237-244。
5.Lin B et al(2001)Neurotrauma 18：389-397。
6.Shao ZH et al(1999)JMol Cell Cardiol 31：1885-95。
7.Gao Z et al(1999)Biochim Biophys Acta 1472：643-50。
8.Yoshino M，Murakami K.(1998)Anal Biochem 257：40-4。
9.Higashitani A et al(1989)Cell Struct Funct 14：617-24。
10.Kimata M et al(2000)Planta Med 66：25-9。
11.Kimata M et al(2000)Clin Exp Allergy 30：501-8。
12.Nakahata N et al(1998)Am J Chin Med 26：311-23。
13.Huang K.(1999)The Pharmacology of Chinese Herbs，2
nd ed.pp.317-404。
14.Davies TA et al(2000)Amyloid 7：153-165。
Claims (7)
1, a kind of be used for the treatment of and/or prophylaxis of acute cerebrovascular, cerebral anoxia, brain contusion after or the postoperative chronic brain injury of cerebral trauma cephalophyma or its sequela, improve senile dementia, myocardial infarction, the Chinese medicine composition of hepatitis or liver cirrhosis is characterised in that it is made by following raw material by weight:
Radix Scutellariae 0.1-10 Rhizoma Chuanxiong 0.1-10 Radix Angelicae Sinensis 0.1-10
Radix Paeoniae Rubra 0.1-10 Cortex Moutan 0.1-10 Flos Carthami 0.1-10
Semen Persicae 0.1-10 Radix Astragali 0.1-10 Radix Glycyrrhizae 0.1-10
Rhizoma Zingiberis Recens 0-6 Ramulus Cinnamomi 0-6.
2,, be characterised in that the weight proportion scope of each raw material is according to the Chinese medicine composition of claim 1:
Radix Scutellariae 0.5-3 Rhizoma Chuanxiong 0.5-3 Radix Angelicae Sinensis 0.5-3
Radix Paeoniae Rubra 0.5-3 Cortex Moutan 0.5-3 Flos Carthami 0.5-3
Semen Persicae 0.5-3 Radix Astragali 0.5-3 Radix Glycyrrhizae 0.2-1.
3,, be characterised in that the weight proportion scope of each raw material is according to the Chinese medicine composition of claim 2:
Radix Scutellariae 1-2 Rhizoma Chuanxiong 1-2 Radix Angelicae Sinensis 1-2
Radix Paeoniae Rubra 1-2 Cortex Moutan 1-2 Flos Carthami 1-2
Semen Persicae 1-2 Radix Astragali 1-2 Radix Glycyrrhizae 0.3-0.8.
4, the method for preparation claim 1,2 or 3 Chinese medicine composition comprises described raw material water decocted and makes oral liquid.
5, as claim 1, the purposes of 2 or 3 described Chinese medicine compositions in medication preparation, be characterised in that this medicine is used for the treatment of cerebrovascular, and can comprise the Western medicine for the treatment of cerebrovascular.
6, claim 1,2 or 3 Chinese medicine composition are characterised in that it is an oral liquid.
7, the purposes of compositions as claimed in claim 1 in medication preparation, wherein said cerebrovascular comprise acute stage after the cerebral ischemia, subacute stage, chronic phase; Acute stage behind the cerebral anoxia, subacute stage, chronic phase; Acute stage behind the cerebral hemorrhage, subacute stage, chronic phase; After the brain contusion and after the operation of cerebral trauma cephalophyma, acute stage and subacute stage, chronic phase; Global brain ischemia and cerebral thrombosis are in earlier stage; Leukoencephalopathy around the dispersivity cerebral malacia that cerebrovascular and cerebral trauma caused and the ventricles of the brain; Carbon monoxide poisoning stupor and tardy encephalopathy (HIE) thereof; And senile dementia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021186235A CN1179741C (en) | 2002-04-26 | 2002-04-26 | Compound Chinese medicine for treating cerebrovascular disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021186235A CN1179741C (en) | 2002-04-26 | 2002-04-26 | Compound Chinese medicine for treating cerebrovascular disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1397324A CN1397324A (en) | 2003-02-19 |
| CN1179741C true CN1179741C (en) | 2004-12-15 |
Family
ID=4744645
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021186235A Expired - Fee Related CN1179741C (en) | 2002-04-26 | 2002-04-26 | Compound Chinese medicine for treating cerebrovascular disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1179741C (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100434096C (en) * | 2006-08-17 | 2008-11-19 | 汪敏 | Drug for treating hepatitis comprising biphenyldicarboxylate |
| CN101850003B (en) * | 2010-05-11 | 2011-08-31 | 李国� | Traditional Chinese medicine and western medicine compound for protecting liver and decreasing enzyme |
| CN101869600A (en) * | 2010-07-05 | 2010-10-27 | 成都中医药大学 | Medicinal composition for treating degenerative change in central nervous system, preparation method and application thereof |
| CN102091246B (en) * | 2010-12-06 | 2012-07-25 | 哈立新 | Chinese medicine composition for treating myocardial infarction |
| CN102631463B (en) * | 2012-03-31 | 2013-10-09 | 于萍萍 | Traditional Chinese medicine (TCM) for treating delayed encephalopathy after acute carbon monoxide poisoning |
| CN102861147B (en) * | 2012-10-23 | 2013-07-31 | 陈兴旺 | Traditional Chinese medicine composition for treating carbon monoxide delayed encephalopathy |
| CN103181954B (en) * | 2013-04-12 | 2014-02-26 | 成都中医药大学 | Medicine composition used for treating neurodegenerative disease as well as preparation method and application thereof |
| CN103566087B (en) * | 2013-10-17 | 2017-04-12 | 宇特金 | Pharmaceutical composition for treating cognitive disorder and application thereof in preparation of medicine for treating Alzheimer disease |
| CN114129696A (en) * | 2014-05-21 | 2022-03-04 | 青州市杏林春膏贴科学研究所 | Composition for preventing and treating senile dementia and preparation method and application thereof |
| CN103977381A (en) * | 2014-05-22 | 2014-08-13 | 刘建国 | Drug for treating carbon monoxide poisoning sequelae |
| CN104547800A (en) * | 2014-12-31 | 2015-04-29 | 东莞市智健医疗科技有限公司 | Use of traditional Chinese medicine preparation in preparation of medicine for treating alcoholic fatty liver |
| CN107737301A (en) * | 2017-11-02 | 2018-02-27 | 向兴中 | A kind of Chinese medicine preparation for treating cerebral hemorrhage etc. |
| CN107812102A (en) * | 2017-12-26 | 2018-03-20 | 李树月 | A kind of pharmaceutical composition for treating cardiovascular and cerebrovascular disease and preparation method thereof, preparation and application |
-
2002
- 2002-04-26 CN CNB021186235A patent/CN1179741C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1397324A (en) | 2003-02-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1179741C (en) | Compound Chinese medicine for treating cerebrovascular disease | |
| CN101690764B (en) | Traditional Chinese medicine for treating cardiac, cerebral and vascular diseases and preparation method thereof | |
| CN1861163A (en) | Traditional Chinese medicine composition for treating kidney-yang deficiency and deficiency of vital energy and blood, its prepn. process | |
| CN101537060B (en) | Medicine for treating AIDS | |
| CN101468154B (en) | Chinese medicine preparation for promoting blood circulation, activating collaterals of hemiplegia patient | |
| CN103784811B (en) | A kind of Chinese herbal medicine treating nyctalopia and preparation method thereof | |
| CN1297291C (en) | Medicine for abstaining from drug addiction and its preparation | |
| CN1561994A (en) | Medicinal compositon containing artemisine extract for treating rheumatoid arthritis and immunologic disease | |
| CN108261505B (en) | Medicine for treating hypertension and cerebral infarction and preparation method thereof | |
| CN1122518C (en) | Medicine for curing gynecopathy | |
| CN103550698A (en) | Traditional Chinese medicine composition for treating acute cholecystitis | |
| CN1186067C (en) | Medicine for curing acute injury of muscle and tendon and its preparation method | |
| CN104740094A (en) | Traditional Chinese medicine for treating migraine | |
| CN112972483A (en) | Application of morinda officinalis oligosaccharide in preparation of medicine for treating body dysfunction caused by altitude anoxia | |
| CN1232283C (en) | Chinese drugs for treatment of coronary heart disease and angina pectoris | |
| CN1045892C (en) | Chinese medicine Guanxintong for preventing and curing coronary heart disease and angina pectoris, and producing process thereof | |
| CN1247213C (en) | Medicinal composition for treating apoplexia, and preparing method and use thereof | |
| CN1814163A (en) | Chinese medicine for treating cardiovascular and cerebrovascular trrombus and preparing method | |
| CN108902430A (en) | A kind of auxiliary conditioning cardiovascular and cerebrovascular disease combined health care products | |
| CN1513542A (en) | Chinese medicinal preparation for treating viral myocarditis and its making method | |
| CN101912547B (en) | Medicament for treating dizziness and preparation method thereof | |
| CN1840152A (en) | Health-caring capsule for middle- and old- aged man and preparation method thereof | |
| CN105126003A (en) | Traditional Chinese medicine composition for preventing and curing madness and preparation method | |
| CN1305517C (en) | Mastoproliferation treating medicine | |
| CN1714839A (en) | Use of medicinal composition in preparing medicine for treating chronic brain blood supply deficiency |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20041215 Termination date: 20130426 |