CN1872081B - Application of kudzuvine root flavone in preparing medicine for treating chronic insufficiency of blood supply for brain - Google Patents
Application of kudzuvine root flavone in preparing medicine for treating chronic insufficiency of blood supply for brain Download PDFInfo
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- CN1872081B CN1872081B CN2005100136661A CN200510013666A CN1872081B CN 1872081 B CN1872081 B CN 1872081B CN 2005100136661 A CN2005100136661 A CN 2005100136661A CN 200510013666 A CN200510013666 A CN 200510013666A CN 1872081 B CN1872081 B CN 1872081B
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Abstract
An application of the pueraria flavone in preparing the medicines for treating chronic cerebral ischemia is disclosed. Its preparing process includes such steps as providing pueraris roots, extracting in water or alcohol, concentrating, depositing in alcohol, purifying by chromatography, eluting and spray drying.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to the application of a kind of Radix Puerariae flavone in preparation treatment chronic insufficient cerebral blood supply medicine.
Background technology
The origin of notion
Chronic insufficient cerebral blood supply (Chronic Cerebral Circulation Inefficiency, CCCI) blood supply that refers to the brain integral level reduces the state of (being lower than 40-60ml/100g cerebral tissue/per minute), but not focal cerebrum ischemia.It is the new name of disease of year proposition surplus in the of external preceding 10.The old age or the presenium patient that often have some to tell subjective symptomss such as nose heave, dizziness repeatedly clinically, except ocular fundus arteriosclerosis, both also not have cranium brain CT unusual for the focal sign of impassivity infringement, and these patients often are diagnosed as " cerebral arteriosclerosis ".As everyone knows, there are difference in the notion of cerebral arteriosclerosis and clinical diagnosis standard long-term.The chaos of conception that the so-called cerebral arteriosclerosis name of disease of always using for fear of people causes, Japanese health ministry has entrusted " about the definition and the diagnostic criteria tutorial class of cerebral arteriosclerosis disease " to study, cerebral arteriosclerosis has been made the corrigendum motion, think that previously cerebral arteriosclerosis, broad sense system include pathological notion of all diseases related that cerebral arteriosclerosis such as lacuna infarction causes; Narrow sense then refers to because cerebral arteriosclerosis causes the conscious slight neural mental symptom that is produced under the pathological state of disturbance of cerebral circulation, the focal sign of impassivity system and to stare at imaging examination unusual.The 16th apoplexy association of Japan formally was referred to as it chronic cerebral circulatory failure (Chronic Cerebral Circulation Inefficiency), i.e. CCCI in 1991.
International research shows that the harm of chronic insufficient cerebral blood supply is a lot.Specifically be summarized as follows:
● the atrophy of cortex atrophy----cortex is the basic pathological change that causes senile dementia
● the neurogenous degeneration of Hippocampus
● frontal lobe, Hippocampus M type cholinoceptor combination rate decline alba are loosened--and-Yi causes occurring hypomnesis, retrograde amnesia occurs
● glial cells hyperplasia---cause brain function to descend
● capillary bed changes
● other neural subjective symptoms obstacle
The diagnosis of CCCI
For CCCI is studied all sidedly, Japan scholar horizontal well is divided into 3 groups with the age the old man more than 60 years old, the A group is: subjective symptoms outbreaks such as dizziness, carebaria are arranged, more than the ocular fundus arteriosclerosis KW II, but do not have also Non Apparent Abnormality person of any focal neurosigns, CT scan; The B group is: except that subjective symptomss such as no dizziness, other conditions are identical with the A group: the C group is cotemporary healthy old men. and these three groups are all carried out CT, MRI, TCD and PET and check. and check result is: (1) TCD measures common carotid artery blood flow and shows that the .A group all significantly lowers for two groups than B, C; (2) PET shows Interhemispheric blood flow, and A group significantly lowers than the C group: (3) MRI finds to have in the A group 55%, have 15% old man to find to have cerebral infarction or lacuna infarction in B and the C group.Its conclusion is: cerebral blood flow lowers near normal 80%, subjective symptomss such as dizziness just may occur; The appearance of mental symptom and nervous symptoms then must be lower than below 80% by blood flow.It should be noted that. the patients' of these dizzy outbreaks TCD and PET to be checked find. the blood flow in carotid artery system and cerebral hemisphere perfusion district thereof and the blood flow of vertebra basilar artery lower equally, therefore clinically dizzy symptom is belonged to vertebro-basilar artery insufficiency without exception seem comprehensive inadequately.Japanese health ministry blood circulation diseases tutorial class (1990) is studied the diagnostic criteria of having worked out CCCI in view of the above, sees the following form 1.
Table 1 chronic insufficient cerebral blood supply (CCCI) diagnostic criteria (one)
(1996) such as nearly rattans make further research 60 routine CCCI patients with said method, except that obtaining above-mentioned similar result of study, still observing CCCI patient further descends with the age growth common carotid artery blood flow, the all sites cerebral blood flow of each cerebral lobe and brain oxidative metabolism rate all descend obviously, think because atherosclerosis risk factors such as hypertension have caused the sclerosis of the mobile arteries and veins of brains.Cause diffuse cerebral blood flow and brain poor metabolism to produce the subjective symptoms of CCCI.Performance is not focal in view of the CCCI cerebral lesion, thus do not occupy transient ischemic attack (transient ischemic attack) category, and drawn more practical CCCI diagnostic criteria (seeing the following form 2).
Table 2 chronic insufficient cerebral blood supply (CCCI) diagnostic criteria (two)
Be born in 2000 the up-to-date diagnostic criteria of CCCI, its particular content is as follows:
" CCCI diagnostic criteria " version in 2000
1. subjective symptomss such as dizziness, headache, head sink;
2. the finding of supporting cerebral arteriosclerosis is arranged: (1) is with hypertension, ocular fundus arteriosclerosis change etc.; Or the vascular murmur of (2) audible and brain perfusion sometimes tremulous pulse;
3. the focal neurosigns that does not have brain;
4.CT having the organic brain of vascular, MRI do not change;
5. get rid of the above-mentioned subjective symptoms that other diseases causes;
6. the age is in principle greater than 60 years old (can be loosened to more than 45 years old);
7. cerebral circulation confirms that cerebral blood flow is low;
8.DSA or TCD prompting brain perfusion tremulous pulse has inaccessible or narrow change.
Compare with early stage version diagnostic criterias in 96 years, this edition standard is opinion, clear and definite more.Its typing sees the following form 3.
The international typing of table 3 chronic insufficient cerebral blood supply
Over past ten years, domestic many scholars compare comprehensive clinical research to CCCI, the blood properties such as blood viscosity fluid rheology index of observing most of CCCI patients reaches Fibrinogen unusually and obviously raises, and thinks that these also have bigger influence to the formation of CCCI or the fluctuation of symptom unusually; CT sees at the end unusual many patients. cranium brain MRI often can detect ischemic focus (the T1 weighted signal is no abnormal, T2 weighting and proton become to protect the slightly high signal of visible stigma point-like); Adopt the TCD dynamic measurement except that common carotid artery, main vascular flow lowers in the brain of still visible many places, for the clinical diagnosis of CCCI has increased new content.
The treatment of CCCI
According to table 1 and table 3, all dizzinesses that the undulatory property growth and decline are arranged, subjective symptoms such as nose heave, CT, MRI do not see vascular brain organic focus person, should belong to simple property CCCI, be considered to the cerebral infarction state of generation last stage, be necessary to carry out positive control, need improve the risk factor (as hypertension, diabetes, hyperlipemia, obesity etc.) of cerebral circulation and removal ischemic cerebrovascular (ICW), preferably adjoin anti-platelet aggregation medicines such as pyridine with aspirin, thiophene chlorine simultaneously, several days clinical subjective symptomss.And TCD or PET measure brain trunk tremulous pulse are arranged (vertebra-basilar artery system or/carotid artery system) blood flow reduction person, belong to compensatory phase CCCI, should take corresponding prevention and health care measure at the ICVD risk factor that exists, symptoms such as clinical appearance dizziness, CT shows ischemic brain material change (cerebral infarction, lacuna infarction), and TCD or PET confirm to have cerebral blood flow attenuating person.Then belong to CCCI II type or III type, should press lacuna infarction or cerebral infarction respectively and handle.
At present, the medicine for the treatment of the CCCI use clinically has: THA: cholinesterase inhibitor, GST-21: maincenter type N cholinoceptor inhibitor, FK506: immunosuppressant, Nimsuperzine:Cox-2 inhibitor etc., all obtained recent preferably clinical efficacy, late result remains further to be studied.Traditional Chinese medicine of China is having unique effect aspect the treatment CCCI.
Through discovering for many years, Radix Puerariae flavone has therapeutical effect for a series of brain diseasess of chronic insufficient cerebral blood supply and especially initiation.
Summary of the invention
The object of the invention is to provide the new purposes of above-mentioned Radix Puerariae flavone aspect the treatment chronic insufficient cerebral blood supply.
The preparation of this medicine is carried out according to the following step:
Be raw material with the Radix Puerariae when Radix Puerariae total flavones prepares, extract 1～10 time at room temperature～100 ℃ merceration or hot reflux with water or 10%～100% ethanol, 2～20 times of each solvent consumptions, concentrate, add alcohol or clarifier sedimentation then, get clear liquor, macroporous resin column chromatography purification, water or 10～100% ethanol elutions, to Radix Puerariae flavone content be 50%～90%, puerarin content is 15%～60%.
Wherein, Radix Puerariae can be Pueraria lobota platymisciums such as Pachyrhizua angulatus, Herba Gelsemii Elegantis, Chai Ge, Caulis menispermi, Emei arrow root.
Above-mentioned Chinese medicine preparation, it can be the dosage form of recording in any pharmacopeia such as granule, capsule, capsule, oral liquid, syrup, pill or powder, the preparation of Chinese medicine preparation also can be carried out with reference to the method for conventional Chinese medicine preparation, but in order to improve drug effect, reduce dosage, compound Chinese medicinal preparation of the present invention preferably adopts following preparation method.
Chronic insufficient cerebral blood supply (CCCI) has close getting in touch with brain symptoms such as dizziness, headaches, but at aspects such as pathogenesis and Therapeutic Method tangible difference is arranged again.At present, for chronic insufficient cerebral blood supply, also mainly be based on the pharmaceutical intervention treatment, there is not clear and definite medicine.The medicine of treatment headache not necessarily has the effect of treatment chronic insufficient cerebral blood supply, even also can cause other untoward reaction.
In order to understand the present invention better, capsule (calling in the following text: " capsule ") treatment chronic insufficient cerebral blood supply rat model below by the observation aforementioned pharmaceutical compositions is dizzy, the influence of learning and memory, and the therapeutical effect of this pharmaceutical composition aspect the treatment chronic insufficient cerebral blood supply is described.
Experimental example: capsule for treating chronic insufficient cerebral blood supply experimentation of the present invention
One, materials and methods
1. animal grouping: 100 of male SD rats, in 10 ages in week, body weight 250 ± 20g is divided into 3 groups at random: Capsules group, nimodipine group, model control group, every group each 20.Capsules group 8 weeks after modeling begin to gavage Chinese medicinal capsule 2g/kg/ days, once a day, and continuous 4 weeks; The nimodipine group substitutes capsule, surplus same Capsules group with equal-volume nimodipine (500ug/kg); Model control group substitutes capsule, surplus same Capsules group with the equal-volume normal saline.
Medicine: nimodipine, nimodipine tablet, Shanxi Yabao Pharmaceutical Co., Ltd. produces, and lot number is that the accurate word (196) of medicine is defended No. 048095 in the Shanxi, every day 3 times, each 20mg, oral; Capsule, Tianjin Tasly Pharmaceutical Co., Ltd.
2. rat chronic cerebral blood supply insufficiency model development: with reference to Torre[Torre Jc, Fortin t, park GA, et al.ChroniccereBRovascular insufficiency induces dementia-induces dementia-like deficits in agedrats.Brain Res, 1992,582 (2): 186-195.] etc. method is made rat both sides ligation of carotid models (2VO).Rat is got the cervical region median incision and cuts off skin through being fixed in behind the 10% chloral hydrate 3.0ml/kg intraperitoneal injection of anesthesia on the operation plate, and passivity is separated each layer tissue, see in the neck that the external carotid artery bifurcated separates vagus nerve, prick bilateral common carotid arteries, layer-by-layer suture with the 4-0 toe-in.Keep 37 ℃-38 ℃ of anus temperature, 23 ℃ of postoperative feeding environment temperature, free diet in the art.
3. learning and memory is measured: adopt Y type maze experiment.Rat is placed in the Y type labyrinth box, began experiment after conforming 3 minutes.The rat of shocking by electricity successively clockwise, the learning and memory in rats achievement has 9 correct required number of shocks to represent to reach in continuous 10 times, how much represent the quality of learning and memory function with reaching 9/10 correct required number of shocks.Laboratory animal respectively at 2VO before, respectively carry out Y type labyrinth test and record achievement behind the 2VO behind 8 weeks, the 2VO behind 12 weeks, the 2VO 16 weeks.
4. measure dizzy incubation period: regulate rotation inducing instrument rotary speed 200r/min.The rat rotation was placed in charged insulating 50 * 50 * 40 experimental boxs on every side in bottom in 1 minute, at once electric shock.(cylindrical rubber of the high 10cm of a diameter 6.5cm is put by experimental box central authorities).Rat stops to jumping onto rubber column escape electric shock and keeping being dizzy incubation period in 30 seconds at rubber column from rotation.Incubation period, long prompt was dizzy serious more more.Each measured once dizzy incubation period to all animals 16 weeks behind 12 weeks, the 2VO behind 8 weeks, the 2VO before 2VO, behind the 2VO.
Two, experimental result
1. capsule is to the influence of chronic insufficient cerebral blood supply learning and memory function: Y shape maze test learning and memory in rats achievement has 9 correct required number of shocks to represent to reach before all rat modelings in continuous 10 times, how much represents the quality of learning and memory function with reaching 9/10 correct required number of shocks.As shown in table 1, correct learning and memory function approximately needs about 18-20 time before the rat 2VO.Behind the rat 2VO, along with time lengthening, the learning and memory achievement descends gradually.The correct learning and memory achievement of 2VO12 week rat is electric shock about 39.5 times, and 16 weeks were about 58.3 times; Nimodipine group and 2VO group no significant difference, P〉0.05.12 weeks of Capsules group, the correct learning and memory achievement with 16 weeks was that shock count is respectively 29.2 and 43.2 times, and organizing with 2VO relatively has notable difference, P＜0.05.The prompting capsule can effectively improve the 2VO learning and memory function.
Table 1 capsule is to the influence of chronic insufficient cerebral blood supply learning and memory function
* compare P＜0.05 with the 2VO group
2. the capsule influence dizzy to the chronic insufficient cerebral blood supply rat: as shown in table 2, be about 96 seconds dizzy incubation period before all rat modelings.Behind the rat 2VO, along with time lengthening increases dizzy incubation period.As shown in table 1, be respectively 17.3 ± 2.3,39.5 ± 4.3,58.3 ± 8.5 the dizzy incubation period that 2VO organizes 8 weeks, 12 weeks, 16 weeks, and notable difference, P arranged before the 2VO〉0.05.Nimodipine treatment each time point of back and 2VO group no significant difference, P〉0.05.Be respectively correct 112.12 ± 16,127.41 ± 26,134.14 ± 31 the dizzy incubation periods in Capsules group 12 week and 16 weeks, notable difference, P＜0.05 relatively arranged with the 2VO group.The prompting capsule can effectively improve dizzy effect incubation period of 2VO rat.
Table 2 capsule is to the dizzy preclinical influence of chronic insufficient cerebral blood supply rat
# and sham operated rats be P＜0.05 relatively; * compare P＜0.05 with the 2VO group
Three, discuss
1992, Torre etc. reported that at first ligation rat bilateral carotid causes the chronic insufficient cerebral blood supply model to succeed.Subsequently studies confirm that 2VO rat hippocampus CA1 district neural degeneration, cortex atrophy, white matter are loose, microglia hypertrophy and capillary bed change etc.The 2VO rat promptly enters chronic phase after 3 weeks, and frontal lobe appears to the 2VO3 rat in rat after 3 months, Hippocampus M type cholinoceptor combination rate descends, and monoamine class mediator changes and the energy metabolism compensatory activates and neuroethology changes.
This experimentation confirms that aspect learning and memory mensuration the correct learning and memory achievement in 12 weeks of Capsules group and 16 weeks is that shock count is respectively 29.2 and 43.2 times, with the 2VO group notable difference, P＜0.05 is arranged relatively.The prompting capsule can effectively improve the 2VO learning and memory function; In dizzy incubation period of influence experiment, be respectively correct 112.12 ± 16,127.41 ± 26,134.14 ± 31 the dizzy incubation periods in 12 weeks of Capsules group and 16 weeks, with the 2VO group notable difference, P＜0.05 are arranged relatively.The prompting capsule can effectively improve dizzy effect incubation period of 2VO rat.
In sum, this experimental result shows that this pharmaceutical composition has the chronic insufficient cerebral blood supply of improvement rat blood circulation, improves effects such as the dizziness that causes because of chronic cerebral ischemia and dysmnesia.
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
Get Herba Gelsemii Elegantis coarse powder 2kg, add 60% ethanol 20L and soak into, hot reflux is extracted 3 times then, each 2 hours, filter merging filtrate, being evaporated to does not have the alcohol flavor, and thin up is to 10L, under 6.0 ℃, stir adding 1% clarifier B solution 300mL, stirred once at interval in per 30 minutes, after 2 hours, add 0.5% clarifier A solution 300mL with quadrat method, feed in raw material back 60 minutes restir once, after 2 hours, coarse filtration is carried out liquid-solid separation with high speed centrifuge again, and it is standby to get clear liquor.Above-mentioned clear liquor is fed in the macroporous resin column (the 4L resin is housed), Radix Puerariae total flavones will be attracted in the resin effectively, earlier being washed to effluent with 5-10L does not have color, the alcohol desorption of reuse 15L50%, the flow velocity of absorption, washing, desorbing be 0.5 times of bed volume per hour.Stripping liquid promptly gets extract product of general flavone of kudzuvine root, the extract obtained puerarin 51% that contains through concentrated, dry, pulverizing.Above-mentioned Radix Puerariae extract is mixed the preparation capsule with suitable adjuvant.
Claims (4)
1. the application of Radix Puerariae flavone in preparation treatment chronic insufficient cerebral blood supply medicine, wherein this flavone is got by following method preparation: be raw material with the Radix Puerariae, extract 1～10 time at room temperature～100 ℃ merceration or hot reflux with 10%～100% ethanol, 2～20 times of each solvent consumptions concentrate then, add alcohol or clarifier sedimentation, get clear liquor, the macroporous resin column chromatography purification, with 10～100% ethanol elutions, collect eluent, spray drying.
2. application according to claim 1, wherein preparation method is: be raw material with the Radix Puerariae, extract 5 times in the room temperature hot reflux with 5% ethanol, 10 times of each solvent consumptions concentrate, add pure sedimentation then, get clear liquor, the macroporous resin column chromatography purification, use 50% ethanol elution, collect eluent, spray drying.
3. the application of Radix Puerariae flavone in the hypomnesis medicine that preparation treatment chronic insufficient cerebral blood supply causes, wherein this flavone is got by following method preparation: be raw material with the Radix Puerariae, extract 1～10 time at room temperature～100 ℃ merceration or hot reflux with 10%～100% ethanol, 2～20 times of each solvent consumptions concentrate then, add alcohol or clarifier sedimentation, get clear liquor, the macroporous resin column chromatography purification, with 10～100% ethanol elutions, collect eluent, spray drying.
4. the application of Radix Puerariae flavone in the vertigo medicament that preparation treatment chronic insufficient cerebral blood supply causes, wherein this flavone is got by following method preparation: be raw material with the Radix Puerariae, extract 1～10 time at room temperature～100 ℃ merceration or hot reflux with 10%～100% ethanol, 2～20 times of each solvent consumptions concentrate then, add alcohol or clarifier sedimentation, get clear liquor, the macroporous resin column chromatography purification, with 10～100% ethanol elutions, collect eluent, spray drying.
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| CN101953880B (en) * | 2009-07-21 | 2013-05-01 | 安康市志朗生物资源应用研究所 | Method for preparing pueraria flavonid |
| CN102127043A (en) * | 2010-12-27 | 2011-07-20 | 武汉工程大学 | Method for extracting and separating pueraria flavonid and pueraria polysaccharide |
| CN102935103A (en) * | 2012-11-18 | 2013-02-20 | 恩施市巨鑫现代农业开发有限公司 | Preparation method for effervescent tablet containing pueraria mirifica flavone |
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| CN1129700A (en) * | 1995-02-23 | 1996-08-28 | 赵爱平 | Extraction and application of Lobed Kudzuvine |
| CN1531930A (en) * | 2003-03-26 | 2004-09-29 | 北京同源医药科技有限公司 | Medicinal composition for curing cerebrovascular disease |
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|---|---|---|---|---|
| CN1129700A (en) * | 1995-02-23 | 1996-08-28 | 赵爱平 | Extraction and application of Lobed Kudzuvine |
| CN1531930A (en) * | 2003-03-26 | 2004-09-29 | 北京同源医药科技有限公司 | Medicinal composition for curing cerebrovascular disease |
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