CN1775219B - Medicinal formulation for preventing and treating ischemic vascular disease, and its preparing method and use - Google Patents
Medicinal formulation for preventing and treating ischemic vascular disease, and its preparing method and use Download PDFInfo
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- CN1775219B CN1775219B CN2005100937231A CN200510093723A CN1775219B CN 1775219 B CN1775219 B CN 1775219B CN 2005100937231 A CN2005100937231 A CN 2005100937231A CN 200510093723 A CN200510093723 A CN 200510093723A CN 1775219 B CN1775219 B CN 1775219B
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- fructus corni
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention discloses a cornus fruit extract and its preparation method, also discloses medicine application of said extract. Said extract contains 25-50% of morroniside and 25-40% of loganin. Said invention also discloses a medicine preparation containing morroniside and loganin for curing various ischemic diseases.
Description
Technical field
The invention provides a kind of pharmaceutical preparation, particularly a kind of pharmaceutical preparation that prevents and treats ischemic vascular disease and its production and use, the field of Chinese medicines belonged to.
Patent application of the present invention is for dividing an application, and the original bill application number is 200310110316.8, and the applying date is December in 2003 30 days, and denomination of invention is a Fructus Corni extract.
Background technology
Ischemic vascular disease mainly is meant vasospasm, thrombosis or the vascular occlusion that artery and vein systemic disease damage causes; Cause organ local circulation and dysfunction, mainly comprise arteriosclerosis, transient ischemic attack, various histoorgan infraction and peripheral vessels obturation etc.Ischemic vascular disease is a harm humans life and healthy commonly encountered diseases and frequently-occurring disease, has sickness rate height, disability rate is high, mortality rate is high and relapse rate is high characteristics, is the principal disease that middle-aged and elderly people causes death and disables.Therefore, finding and develop the medicine of preventing and treating ischemic vascular disease has great importance.Fructus Corni is the Chinese medicine of liver and kidney tonifying, essence astringing and desertion stemming; The compound treatment various disease is formed in normal clinically and other drug matching; But rarely found have the Fructus Corni single medicinal material to treat disease; Especially the research report of effective ingredient is few in the Fructus Corni extract, does not see the report that this chemical compound control ischemic vascular disease is arranged both at home and abroad as yet.Fructus Corni extract is product (the Cornus total glycosides that from Cornaceae plant Fructus Corni Cornus officinalis sarcocarp, extracts; Fructus Corni extract), wherein mainly comprise morroniside (morroniside), meliatin (loganin is a loganin) etc.The present invention extracts through specific method for distilling and obtains the extract of Fructus Corni, and has invented the new pharmaceutical use of this extract.
Summary of the invention
Purpose of the present invention has been to provide the extract and the method for distilling thereof of Fructus Corni; Another object of the present invention has been to provide the new pharmaceutical use of Fructus Corni extract; Another object of the present invention has been to provide a kind of pharmaceutical preparation of new treatment ischemic vascular disease.
Fructus Corni extract according to the invention contains morroniside 25-50%, meliatin 25-40%, and the two total content accounts for 50-90%.(by weight percentage)
The invention described above Fructus Corni extract can be used following method preparation:
Fructus Corni medical material water decocts 2-4 time, and amount of water 3-14 times, decocting time 1-4 hour; Merge decoction liquor, filter the back concentrating under reduced pressure, cold preservation is subsequent use after filtering;
Above-mentioned spissated Fructus Corni aqueous extract is crossed macroporous adsorptive resins, and the messenger drug liquid stream is crossed full post, carries out gradient elution with deionized water, 5%-95% ethanol successively, and concentrating under reduced pressure becomes extractum;
The isolating extractum of macroporous adsorbent resin is made with extra care with organic solvents such as ethyl acetate or ethanol, got effective part extract.
Perhaps Fructus Corni medical material water decocts 2-4 time, and amount of water 3-14 times, time 1-4 hour.Merge decoction liquor, filter the back concentrating under reduced pressure, adding ethanol, to transfer to determining alcohol be 50%-90%, cold preservation 12-48 hour, filters decompression filtrate recycling ethanol.
Above-mentioned spissated alcohol deposit fluid is crossed the HP20 macroporous adsorptive resins, after Al
2O
3Chromatographic column, the messenger drug liquid stream is crossed full post, carries out gradient elution with deionized water, 5%-95% ethanol successively, and concentrating under reduced pressure becomes extractum, lyophilization.The said Fructus Corni extract of the present invention is meant through said method and extracts the effective site that obtains.
The assay method of effective site: the said extracted Tetramune is used thin layer chromatography carry out qualitative analysis.And the said extracted Tetramune is used high performance liquid chromatograph carry out quantitative analysis, chromatographic condition: the Lichrospher-C18 chromatographic column, mobile phase methanol-water (30: 70) detects wavelength 240nm, flow velocity 1.0ml/ minute.The check and analysis result: morroniside content accounts for 25-50%, meliatin content accounts for 25-40%, and the two total content accounts for 50-90% (by weight percentage).
Fructus Corni extract of the present invention can add adjuvant and be prepared into the various clinical pharmaceutical dosage form by practice of pharmacy, comprises the dosage form of oral formulations or parenterai administration.Said oral formulations is selected from any in tablet, capsule, pill, granule, suspensoid, drop pill, the oral liquid; Said non-intestinal is selected from a kind of in the middle of injection, aerosol, suppository or the subcutaneous administration dosage form to dosage form.
Said adjuvant is meant conventional excipient, like solvent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent etc.
The present invention discloses the pharmaceutical preparation of a kind of treatment ischemic vascular disease, it is characterized in that said preparation contains 5-95% morroniside, 5-95% meliatin; Preferred 10-80% morroniside, 10-80% meliatin; More preferably 20-60% morroniside, 60-20% meliatin.Also can contain acceptable accessories in this pharmaceutical preparation.Described morroniside, meliatin all can be selected the purification article of selling on the market for use.
Adjuvant such as sucrose, citric acid, aspartame, potassium sorbate, essence, Pulvis Talci and lactose.The Fructus Corni extract that method for distilling of the present invention obtains, content is clear and definite, through experiment showed, having definite curative effect aspect the treatment ischemic vascular disease, can be used for preparing the medicine of treatment ischemic cerebrocardiac disease or peripheral angiopathy etc.
Said ischemic vascular disease is meant vasospasm, thrombosis or the vascular occlusion that artery and vein systemic disease damage causes, the various organ local circulation or the dysfunction that are perhaps caused.Said ischemic vascular disease is meant any in arteriosclerosis, transient ischemic attack or various histoorgan infraction or the peripheral vessels obturation.
The pathomechanism of said ischemic vascular disease shows as vasospasm or luminal stenosis due to a variety of causes, vascular endothelial injury, and platelet aggregation property increases, thrombosis, or embolus blocks, and causes tissue ischemia so that downright bad.
Fructus Corni extract of the present invention has following pharmacological action: comprise anticoagulant, alleviate acute cerebral infarction property blood vessel injury, reduce to block ischemia half dark space area; Reduce intracellular calcium concentration, improve energy and substance metabolism after the acute GBI anoxia, improve ability of learning and memory, acetylcholine esterase inhibition is active with MAO-B, and the inhibition free radical increases and lipid peroxidation.
Following experimental example further specifies the present invention, but does not constitute the qualification to protection domain that the present invention requires.
Experimental example 1 Fructus Corni extract is to the influence of rat platelet aggregation property
Experiment purpose: under normal circumstances, platelet is moved in blood vessel with dispersity.But when blood vessel injury, blood flow changed or receive the chemical substance stimulation, form then took place and changes, sticks, assembles and discharge in platelet, in thrombosis, plays an important role.Platelet aggregation property increases reference index and the thrombotic risk factor that also can be used as the diagnosis hypercoagulability.The influence of Fructus Corni extract to rat platelet aggregation property observed in this research.
Experimental technique: male SD rat continuous irrigation stomach gives Fructus Corni extract after 14 days, experimentizes.Get blood and be administered once in preceding 1 hour, pentobarbital sodium anesthesia.Abdominal aortic blood, 3.8% sodium citrate anticoagulant (1: 9), centrifugal preparation rich platelet (PRP) and platelet poor plasma (PPP) are with the platelet aggregation of the Shanghai Si Long MPG3E of company type platelet aggregation instrument mensuration ADP (1.25mmol/L) and thrombin induction.
Experimental result: Fructus Corni extract has remarkable reduction ADP and the accumulative effect of thrombin hyperamization platelet (table 1).Show that this chemical compound helps preventing and treating thrombosis in the various histoorgan blood vessels.
Table 1 Fructus Corni extract to rat platelet aggregation influence
M ± SD; * p 0.05, compare with matched group
Experimental example 2 Fructus Corni extracts cause the influence of acute GBI model to the disconnected cranium of mice
Experiment purpose: disconnected cranium causes the model that acute GBI mouse model is the rapid screening anti-cerebral ischemia anoxic medicine used always, and this model can be simulated the metabolic reduction of brain self-energy, causes neuronal death.Some energy supply materials that have in the disconnected cranium hindbrain are still enough kept the mice mouth breathing of certain hour, so the available mouth breathing time is represented the time that the energy supply material is exhausted.This research is intended to observe the protective effect of Fructus Corni extract to chmice acute GBI model.
Experimental technique: Kunming mouse, male and female half and half, body weight 18-22 gram.Give mouse stomach administration every day 2 times, successive administration 5 days.In administration in the morning in the 6th day disconnected cranium after 1 hour, dehisce to breathe the persistent period continuously with stopwatch record mice, be death greater than 5 seconds at interval with twice breathing.
Experimental result: Fructus Corni extract is irritated the time (table 2) that the appetite clothes can prolong mouth breathing behind the disconnected cranium of mice, shows that Fructus Corni extract has the effect that energy metabolism that the antagonism cerebral hypoxia ischemia causes reduces the neural cell injury that causes.
Table 2 Fructus Corni extract causes the influence of mouth breathing time behind the acute GBI to the disconnected cranium of mice
M ± SD; * p 0.05, * * p 0.01, compare with matched group
Experimental example 3 Fructus Corni extracts cause the influence of local organization ischemic necrosis mouse model to radical damage
Experiment purpose: increased by oxygen-derived free radicals and to cause vascular endothelial cell damage, platelet aggregation forms thrombosis, and causing the local organization ischemic necrosis is the common pathological change of ischemic cerebrocardiac disease and peripheral angiopathy.The modeling principle of this experiment is that photoactive substance (rose-red) is injected mouse tail vein; Photochemical reaction takes place in the cold light source irradiation mice cranium portion with the 560nm wavelength, generates a large amount of oxygen-derived free radicals; Cause vascular endothelial cell damage; Platelet aggregation forms thrombosis in irradiated region, local cortical tissue ischemic necrosis.This research is intended to observe Fructus Corni extract causes local organization ischemic necrosis and ischemia half dark space to radical damage influence.
Experimental technique: give mouse gavaging various dose Fructus Corni extract, modeling after 15 days.Photoactive substance (rose-red) is injected mouse tail vein, with the cold light source irradiation mice cranium portion of 560nm wavelength.After modeling, inject the Yi Wensilan dyestuff through the tongue vein in 3 hours, put to death animal after 1 hour.Get cerebral tissue after the execution and process homogenate, and with the optical density of the average cerebral tissue of colorimetric method for determining.The infraction severe patient, dyeing is dark, and optical density is big, and ischemia half dark space area is big.
Experimental result: irritate the optical density that the clothes Fructus Corni extract can reduce model mice cerebral tissue Yi Wensilan, and reduce the area (table 3) of model mice ischemia half dark space.Showing that Fructus Corni extract can alleviate owing to oxygen-derived free radicals increases causes blood vessel injury and thrombosis, helps preventing and treating the blood vessel injury and the tissue necrosis of ischemic vascular disease.
Table 3 Fructus Corni extract is to the influence of damage of radical damage induction of vascular and cerebral infarction mouse model
M ± SD; * p 0.05, compare with model group
Ischemia half blanking bar :+, ++, +++, ++ ++ represent area ascending successively.
Experimental example 4 Fructus Corni extracts cause the influence of focal tissue ischemia rat model to arterial occlusion
Experiment purpose: it is the common pathological change of ischemic cerebrocardiac disease and peripheral angiopathy that the concentration of cytoplasm calcium ion that is caused by ischemia increases unusually, and calcium ion increases also can cause vasoconstriction or spasm.The concentration of cytoplasm calcium ion that is caused by ischemia increases unusually, can make the phospholipase that receives regulation of calcium, protease, Cobra venom endonuclease etc. be activated to cause membrane phospholipid to decompose and cytoskeleton destroys, and cell produces irreversible damage.This research be intended to observe Fructus Corni extract to ischemia after the influence of calcium ion concentration in the endochylema.
Experimental technique: (1) modelling: experimental rat is in administration in the 14th day row intraperitoneal anesthesia after 30 minutes; Make the diagonal otch about in the of in right external auditory canal and right outer canthus line mid point; Be separated to abundant exposure middle cerebral artery, be affixed on middle cerebral artery and anterior cerebral veins infall, really block with the microscopic examination blood flow of middle cerebral artery after 30 minutes with the filter paper bar that is soaked with 50% ferric chloride; Remove filter paper, normal saline flushing, stitching.(2) mensuration of calcium ion fluorescence intensity in the hippocampal cell: after the rat modeling 24 hours, broken end was got brain and is placed in the artificial cerebrospinal fluid, cuts the brain sheet of 300 micron thick in the optic chiasma level.Add artificial cerebrospinal fluid 400 microlitres that contain 5uM Fluo-3/AM, hatch laser confocal microscope mensuration hippocampus intracellular calcium fluorescence intensity after 1 hour.
Experimental result: every group of right side is the ischemia side, and calcium ion concentration increases than strong side (left side).Left and right sides brain calcium ion concentration difference compares, and the interior calcium ion fluorescence intensity of model group hippocampal cell increases obvious than matched group, and model is set up.Fructus Corni extract medication group reduces (table 4) than calcium ion concentration in the model group hippocampal cell.The effect that shows calcium ion concentration in this chemical compound reduction endochylema helps blood vessel dilating and protection ischemic tissue, improves cell survival rate, and is significant to the control of ischemic vascular disease.
Table 4 Fructus Corni extract is to the influence of ischemia model rat hippocampus intracellular calcium concentration
M ± SD; * p 0.05, compare with matched group
Experimental example 5 Fructus Corni extracts are to the influence of bilateral ligation rat model learning and memory function
Experiment purpose: the result of histoorgan ischemia and pathological change thereof causes hypofunction even forfeiture.Long-term cerebral ischemia can cause learning and memory function to descend or vascular dementia.The influence of Fructus Corni extract to 8 week of bilateral ligation back learning and memory function observed in this research.
Model preparation and administration: the SD rat, intraperitoneal injection of anesthesia separates bilateral common carotid arteries, with No. 1 permanent ligation of silk thread, suture muscles skin.Prevention is irritated stomach and is given 2 weeks of Fructus Corni extract, 8 weeks of postoperative gastric infusion before the art.
Darkness avoidance test: detect the passive avoidance memory function.Adopt rat to keep away camera bellows, experimentize in the 8th week of postoperative, trained in first day, rat is put into bright chamber, make it get into the darkroom and shocked by electricity 2 times, test after 24 hours, the record rat gets into the number of times and the incubation period in darkroom, and classification.Two forelimbs get into the darkroom and are designated as 1 fen; Three forelimbs get into the darkroom and are designated as 2 fens; Extremity get into the darkroom simultaneously and are designated as 3 fens.Compare between group as a result, carry out the t check.
Channel-type water maze method: in beginning training in the 8th week of postoperative.Experiment divides to be carried out in 4 days, and training 2 cecums were 2 times in the 1st day, and training 3 cecums were 2 times in the 2nd day; Training 4 cecums were 2 times in the 3rd day, the 4th day survey 4 cecums.Each training time is limited to 2min, and overtime person adopts artificial guiding, presses the 2min timing.Every each training and testing of rat all writes down time (time of advent) of reaching home and the number of times (errors) that gets into cecum.As school grade, 4 times of advent cecum testing period and errors be as the memory achievement with the average of 4 cecum times of advent training period and errors, as a result between group relatively, carry out the t check.
Morris water maze method:, in beginning training in the 8th week of postoperative.Experiment divides to be carried out in 5 days, trained every day 2 times.Training in the 1st day 2 times, going into the position, pond is that platform institute is to quadrant and adjacent quadrant.In the quadrant limit 1/2 radian place with the rat head towards the pool wall entry.Training time is limited to 2min, and overtime person adopts artificial guiding, presses the 2min timing.The track of the time of swimming out of, distance, search platform is all write down in every each training of rat.Compare between group as a result, carry out the t check.
Experimental result: this experiment finds that the long-term ligation of bilateral common carotid arteries makes rat produce learning memory disorder.Fructus Corni extract can improve the learning and memory of rat model, shows time of swimming out of that can shorten in the water maze test and distance, reduces errors number (table 5-7); In keeping away dark test, can prolong incubation period, reduce errors number (table 8).Show that Fructus Corni extract can improve the dysfunction that long-term histoorgan ischemia causes.
Table 5 Fructus Corni extract is swum out of the time influence of (second) to bilateral ligation rat model Morris water maze
M ± SD, compare with model group: * P 0.05, * * P < 0.01
Table 6 Fructus Corni extract to bilateral ligation rat model Morris water maze swim out of the distance (centimetre) influence
M ± SD, compare with model group: * P 0.05, * * P < 0.01
Table 7 Fructus Corni extract is to the influence of bilateral ligation rat model channel-type water maze learning and memory
M ± SD, compare with model group: * P 0.05, * * P < 0.01
Table 8 Fructus Corni extract is kept away the influence of dark experiment to the bilateral ligation rat model
M ± SD, compare with model group: * P 0.05, * * P < 0.01
Experimental example 6 Fructus Corni extracts are to the influence of bilateral ligation rat model cerebral cortex acetylcholine esterase active
Experiment purpose: Acetylcholinesterase (AchE) is the enzyme of hydrolysis neurotransmitter acetylcholine in the brain.The AchE inhibitor can slow down the catabolism of acetylcholine, improves ability of learning and memory.This research is observed Fructus Corni extract to the active influence of the AchE of ischemia rat cerebral tissue.
Experimental technique: after rat cerebral cortex homogenate is centrifugal, gets supernatant and measure the AchE activity with biochemical method.
Experimental result: long-term cerebral ischemic model rat cerebral cortex AchE is active obviously to be strengthened.Fructus Corni extract can obviously suppress rat model cerebral cortex AchE active (table 9).
Table 9 Fructus Corni extract is to the active influence of bilateral ligation rat model cerebral cortex AchE
M ± SD, compare with model group: * P 0.05, * * P < 0.01
Experimental example 7 Fructus Corni extracts are to the active influence of bilateral ligation rat model cerebral cortex MAO-B
Experiment purpose: monoamine oxidase, MAO extensively is distributed in animal tissue, mainly is positioned at the cell mitochondrial part, but the various monoaminess of its catalysis make its deamination generate corresponding aldehyde, further is oxidized to acid or makes aldehyde change into alcohol to carry out next step metabolism again.MAO-B (MAO-B) increases with the MAO-B activity that increases multiple tissue in age with old and feeble in close relations.The MAO-B inhibitor can be used for treating cardiovascular and cerebrovascular disease, parkinson disease, senile dementia and slow down aging in recent years.This research is observed Fructus Corni extract to the active influence of bilateral ligation rat model cerebral cortex MAO-B.
Experimental technique: after big rat brain tissue homogenate is centrifugal, gets supernatant and measure the MAO-B activity with biochemical method.
Experimental result: bilateral ligation rat cerebral cortex MAO-B specific activity matched group obviously increases.Fructus Corni extract can obviously suppress bilateral ligation rat model cerebral cortex MAO-B active (table 10).
Table 10 Fructus Corni extract is to the active influence of bilateral ligation rat model cerebral cortex MAO-B
M ± SD compares with model group: * P < 0.05
Experimental example 8 Fructus Corni extract qualitative analyses according to the invention
Extract of the present invention and goods application high performance liquid chromatograph thereof are carried out quantitative analysis, chromatographic condition: the Lichrospher-C18 chromatographic column, mobile phase methanol-water (30: 70) detects wavelength 240nm, flow velocity 1.0ml/ minute.The check and analysis result:
The effect of experimental example 9 morronisides and meliatin compositions (morroniside accounts for 45% for morroniside combined with loganin, MCL, and meliatin accounts for 40%, the mixture of medical starch 15%) control cerebral hypoxia ischemia
1.MCL improve ischemia-reperfusion mouse model ability of learning and memory
Experimental technique: kunming mice, body weight 20 ± 2g, continuous irrigation stomach give MCL7 days, press from both sides repeatedly with bilateral common carotid arteries in 1 hour after the last administration and close the method that logical (folder closes 2 times, each 15min, the logical again 10min in centre) merge afterbody blood-letting again and set up the cerebral ischemia reperfusion model.Postoperative began to carry out Morris water maze and the test of mice diving tower on the 7th day, detected its ability of learning and memory.
The Morris water maze is measured: the Morris water maze mainly is made up of with automatic video and analytical system two parts the round pool of diameter 1.4m.Depth of water 15cm, 25 ℃ ± 2 ℃ of water temperatures add an amount of milk powder water are creamy white; Every mouse head is coated with black, and the top, pond is put one and penetrated picture head collection mice swimming track, training in first day 2 times; Go into the position, pond and be platform institute to quadrant and adjacent quadrant, in the quadrant limit 1/2 radian place with the mice head towards the pool wall entry, 120S does not find platform person; It is caused platform, place its Learning and Memory of 30S guiding.2nd, retest in 3 and 4 days; Data acquisition and processing (DAP) keeps watch on automatically by image and processing system is accomplished.
Mice diving tower experiment: measure the mice passive avoidance response.Each group mice is put into reaction chamber respectively adapt to 3min, pass to the 36V alternating current, training 5min; Behind the 24h mice is put on the copper grid, energising, the record mice jumps onto the number of times (errors number) that jumps off in the time (reaction period) of diving tower, the time (incubation period) of jumping off for the first time, the 5min for the first time.
Experimental result: tangible learning memory disorder can occur behind the mouse brain hypoxic-ischemic; Show as the Morris water maze test and swim out of the prolongation that the time increases and swim out of distance; The step down test reaction period prolongs and shorten incubation period; Prompting MCL has the effect that improves the model mice ability of learning and memory, shows as the shortening that the Morris water maze test is swum out of the time and swum out of distance.
Table 11MCL swims out of the influence (n=10) of time to ischemia-reperfusion mouse model Morris water maze
M ± SD, compare with model group: * P 0.05, * * P < 0.01
Table 12MCL irritates the influence (n=10) that mouse model Morris water maze is swum out of distance again to ischemia
M ± SD, compare with model group: * P 0.05, * * P < 0.01
Table 13 diving tower method is observed MCL irritates the mouse model learning and memory function again to ischemia influence (n=10)
M ± SD, compare with model group: * P 0.05, * * P < 0.01
Irritate the mouse model lipid peroxidation again 2.MCL suppress ischemia
Experimental technique: kunming mice, 20 ± 2g is after the random packet; The continuous irrigation stomach is given MCL7 days; Pressed from both sides repeatedly with bilateral common carotid arteries in 1 hour after the last administration and close again the method that logical (folder closes 2 times, each 15min, the logical again 10min in centre) merge afterbody blood-letting and set up the cerebral hypoxia ischemia model.After 14 days, broken end is got brain rapidly, separates cerebral cortex, measures lipid peroxide malonaldehyde (MDA) content in the cerebral tissue with sulfo-barbital (TAB) method.Experimental result: MCL irritates clothes and can reduce ischemia and irritate mouse brain again and organize MDA content, shows that this medicine can suppress lipid peroxidation (table 14), has antioxidation.
Table 145-HMF irritates mouse brain again to ischemia and organizes the influence of MDA content (n=10)
M ± SD, compare with model group: * P 0.05, * * P < 0.01
In sum, the product that from Fructus Corni, extract to obtain, or the composite preparation of forming by morroniside and meliatin; Can obviously reduce platelet aggregation, alleviate the blood vessel injury of histoorgan, reduce ischemia half dark space area by ADP and thrombin induction; Reduce intracellular calcium concentration; Improve energy and substance metabolism behind the histoorgan hypoxic-ischemic, improve the ability of learning and memory of long-term cerebral ischemia animal model, acetylcholine esterase inhibition and MAO-B are active; And can obviously improve the learning and memory function of ischemia-reperfusion animal model, suppress the organ-tissue lipid peroxidation.Show that this pharmaceutical preparation has the effect of control ischemic vascular disease.Can be used for treating the artery and vein systemic disease and decrease vasospasm, thrombosis or the vascular occlusion that causes, perhaps cause various organ local circulation and dysfunction.Be mainly used in treatment arteriosclerosis, ischemic cerebrocardiac disease and peripheral angiopathy etc. clinically.
Following examples all can reach the effect of above-mentioned experimental example.
Preferred forms
Embodiment 1The preparation of Fructus Corni extract
Fructus Corni medical material water decocts 3 times, 6 times of amount of water, 2 hours time.Merge 3 times decoction liquor, filter the back concentrating under reduced pressure, cold preservation is subsequent use after filtering; Get spissated Fructus Corni water extraction, last HP20 macroporous adsorptive resins, the messenger drug liquid stream is crossed full post, carries out gradient elution with deionized water, 30%, 50% ethanol successively, collects 50% alcoholic acid eluent, and concentrating under reduced pressure becomes extractum; The isolating product extractum of macroporous adsorbent resin is used alcohol extraction, remove organic solvent, concentrate, drying obtains solid product.Yield 2.5%.
Embodiment 2The preparation of Fructus Corni extract
Fructus Corni medical material water decocts 3 times, 6 times of amount of water, 2 hours time.Merge 3 times decoction liquor, filter the back concentrating under reduced pressure, adding ethanol, to transfer to determining alcohol be 70%, and cold preservation 24 hours is filtered, and behind the decompression filtrate recycling ethanol, cold preservation is subsequent use.
Get above-mentioned Fructus Corni water extract-alcohol precipitation extracting solution, last HP20 macroporous adsorptive resins, the messenger drug liquid stream is crossed full post, carries out gradient elution with deionized water, 30%, 50% ethanol successively, collects 50% alcoholic acid eluent, and concentrating under reduced pressure becomes extractum.
With Al on the isolating fluid extract of macroporous adsorbent resin
2O
3Chromatographic column is made with extra care with ethanol elution, and lyophilizing obtains solid product, yield 2.3%.
Through the high performance liquid chromatograph analysis, morroniside content accounts for 25-50% in the said product, meliatin content accounts for 25-40%, and the two total content accounts for 50-90%.
Embodiment 3Capsule
Fructus Corni extract 300g medical starch 1000g of the present invention, mix homogeneously, the capsule of packing into No. 1, every 0.35g, each oral 1-2 grain, twice of every day.
Embodiment 4Tablet
Fructus Corni extract 300g of the present invention, carboxymethyl cellulose 40g, lactose 50g, magnesium stearate 4g.Said components is pulverized, mixed, tabletting is processed tablet, every 0.4g, each 3, every day 3 times.
Embodiment 5Capsule
Morroniside 140g, meliatin 120g, medical starch 1000g, mix homogeneously, the capsule of packing into No. 1, every 0.35g, each oral 1-2 grain, twice of every day.
Embodiment 6Tablet
Morroniside 140g, meliatin 120g, carboxymethyl cellulose 40g, lactose 50g, magnesium stearate 4g.Said components is pulverized, mixed, tabletting is processed tablet, every 0.4g, each 3, every day 3 times.
Embodiment 7Capsule
Morroniside 300g, meliatin 200g, medical starch 800g, mix homogeneously, the capsule of packing into No. 1, every 0.20g, each oral 1-2 grain, twice of every day.
Embodiment 8Capsule
Morroniside 400g, meliatin 200g, medical starch 800g, mix homogeneously, the capsule of packing into No. 1.
Embodiment 9Capsule
Morroniside 300g, meliatin 500g, medical starch 800g, mix homogeneously, the capsule of packing into No. 1.
Claims (4)
1. pharmaceutical preparation is characterized in that the crude drug of said preparation consists of 45% morroniside and 40% meliatin.
2. the method for preparing of pharmaceutical preparation as claimed in claim 1 is characterized in that the used crude drug of this method is 45% morroniside and 40% meliatin.
3. according to claim 1 or claim 2 the application of pharmaceutical preparation in preparation control cerebral hypoxia ischemia medicine.
4. application as claimed in claim 3 is characterized in that described control cerebral hypoxia ischemia is meant the raising ability of learning and memory or suppresses lipid peroxidation.
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| CN 02159502 CN1424319A (en) | 2002-12-30 | 2002-12-30 | Extracts of cornus officinalis and its preparation and use |
| CN02159502.X | 2002-12-30 | ||
| CN2005100937231A CN1775219B (en) | 2002-12-30 | 2003-12-30 | Medicinal formulation for preventing and treating ischemic vascular disease, and its preparing method and use |
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| CN1148968A (en) * | 1996-09-11 | 1997-05-07 | 中日友好临床医学研究所 | Extract of Asiatic cornelian cherry with immunosuppression and preparation thereof |
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