CN1424319A - Extracts of cornus officinalis and its preparation and use - Google Patents

Extracts of cornus officinalis and its preparation and use Download PDF

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CN1424319A
CN1424319A CN 02159502 CN02159502A CN1424319A CN 1424319 A CN1424319 A CN 1424319A CN 02159502 CN02159502 CN 02159502 CN 02159502 A CN02159502 A CN 02159502A CN 1424319 A CN1424319 A CN 1424319A
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extract
fructus corni
ischemic
water
ethanol
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李林
赵玲
张兰
叶翠飞
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Xuanwu Hospital
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Xuanwu Hospital
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Priority to CNB2003101103168A priority patent/CN100364545C/en
Priority to CN2005100937231A priority patent/CN1775219B/en
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Abstract

An extract of dogwood fruit, its preparing process and its application in preparing medicines are disclosed. Said extract can be clinically used to treat arteriosclerosis, transient ischemic attack, tissue organs infarction and peripheral vessel obliteration.

Description

Fructus Corni extract and its production and use
Technical field
The invention provides a kind of Fructus Corni extract, also relate to the purposes of this preparation method of extract and this extract, belong to the field of Chinese medicines.
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, histoorgan infraction and surrounding blood vessel obturation etc.Ischemic vascular disease is harm humans life and healthy common disease and frequently-occurring disease, has sickness rate height, disability rate height, mortality ratio height and the high characteristics of recurrence rate, is the principal disease that the elderly causes death and disables.Therefore, finding and develop the medicine of preventing and treating ischemic vascular disease has great importance.Skunk bush be tonify the liver and kidney, traditional Chinese medicine that puckery essence is taken off admittedly, the compound treatment various disease is formed in normal clinically and other drug matching, but rarely found have the skunk bush single medicinal material to treat disease, especially the research report of the total glycoside compound of Fructus Corni extract is few, does not see the report that this compound control ischemic vascular disease is arranged both at home and abroad as yet.The present invention extracts by specific extracting method and obtains the extract of skunk bush, and has invented the new pharmaceutical use of this extract.
Summary of the invention
The invention provides the extract and the extracting method thereof of skunk bush.
The present invention also provides the new pharmaceutical use of Fructus Corni extract.
Being prepared as follows of Fructus Corni extract of the present invention:
Skunk bush medicinal material water decocts 2-4 time, and amount of water 3-10 times, decocting time 1-4 hour.Merge decoction liquor, filter the back concentrating under reduced pressure, refrigeration is standby after filtering.
Perhaps skunk bush medicinal material water decocts 2-4 time, and amount of water 3-10 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%, refrigerate 12-48 hour, filters, and behind the decompression filtrate recycling ethanol, with n-butanol extraction 3-5 time, recovery propyl carbinol, extraction liquid refrigerates standby.
With above-mentioned spissated skunk bush aqueous extract or water extract-alcohol precipitation extracting solution, last macroporous adsorptive resins makes soup flow through full post, carries out gradient elution with deionized water, 10%-95% ethanol successively, and concentrating under reduced pressure becomes medicinal extract.
The isolating total glycoside extract of macroporous adsorbent resin is made with extra care with organic solvents such as ethyl acetate or ethanol, got efficient part.
The said Fructus Corni extract of the present invention is meant through aforesaid method and extracts the efficient part that obtains.
The said Fructus Corni extract of the present invention is total glycoside compound (the Cornus total glycosides that extracts from Cornaceae plant skunk bush Cornus pulp, CTG), comprising cornin (Cornin is verbenaloside Verbenalin), morroniside (morroniside), Methylmorroniside (methylmorroniside), Ma Qiansu (loganin is a loganin), dehydrogenation Ma Qiansu (dehydrologanin), iridoid glycoside (iridoid glycosides), sweroside (sweroside), saponin(e etc.
The measuring method of efficient part: 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: total glycosides content accounts for more than 50% of Fructus Corni extract.
The Fructus Corni extract that extracting method of the present invention obtains the experiment proved that, having definite curative effect aspect the treatment ischemic vascular disease, can be used for preparing the medicine of treatment ischemic angiocardiopathy and cerebrovascular disease or peripheral angiopathy etc.
Therefore, the present invention also comprises the application of Fructus Corni extract in preparation control ischemic vascular disease medicine.Said ischemic vascular disease is meant vasospasm, thrombosis or the vascular occlusion that artery and vein systemic disease damage causes, the organ local circulation or the dysfunction that are perhaps caused.Specifically, this ischemic vascular disease is meant any in arteriosclerosis, transient ischemic attack or histoorgan infraction or the surrounding blood vessel obturation.The pathomechanism of said ischemic vascular disease shows as vasospasm or luminal stenosis due to a variety of causes, blood vessel endothelium injury, and platelet aggregation increases, thrombosis, or embolus blocks, and causes tissue ischemia so that downright bad.Its pharmacological action of Fructus Corni extract of the present invention also comprises anticoagulant, alleviates the acute cerebral infarction blood vessel injury, reduces to block ischemic half dark space area; Reduce intracellular calcium concentration, improve energy and substance metabolism after the acute global brain ischemia anoxic, improve ability of learning and memory, acetylcholine esterase inhibition and monoamine oxidase-B activity. Experimental example 1.Fructus Corni extract (CTG) is to the influence of rat platelet aggregation
Experiment purpose: under normal circumstances, thrombocyte moves in blood vessel with dispersion state.But when blood vessel injury, blood flow changed or be subjected to the chemical substance stimulation, form then took place and changes, sticks, assembles and discharge in thrombocyte, plays an important role in thrombosis.Platelet aggregation increases reference index and the thrombotic risk factor that also can be used as the diagnosis hypercoagulative state.The influence of Fructus Corni extract to rat platelet aggregation 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, vetanarcol anesthesia.Abdominal aortic blood, 3.8% Sodium Citrate anti-freezing (1: 9), centrifugal preparation platelet rich plasma (PRP) and platelet poor plasma (PPP) are with the platelet aggregation of the Shanghai MPG3E of Si Long company type platelet aggregation instrument mensuration ADP (1.25mmol/L) and thrombin induction.
Experimental result: Fructus Corni extract has remarkable reduction ADP and zymoplasm hyperamization platelet accumulative effect (table 1).Show that this compound helps preventing and treating thrombosis in the multiple histoorgan blood vessel.
Table 1. Fructus Corni extract (CTG) to rat platelet aggregation influence group number of animals MA (%)
ADP induces thrombin induction control group 10 60.0 ± 5.8 58.9 ± 6.2 hydergines (positive control drug), 9 44.1 ± 6.6*, 39.1 ± 5.8*CTG 0.33g/kg, 9 50.7 ± 9.5 44.6 ± 6.7*CTG 1g/kg, 10 46.9 ± 5.1*, 37.9 ± 9.2*CTG 3g/kg, 10 37.7 ± 5.7*, 35.8 ± 6.5*
M ± SD; * p<0.05 is compared with control group Experimental example 2Fructus Corni extract causes the influence of acute global brain ischemia model to the disconnected cranium of mouse
Experiment purpose: disconnected cranium causes the model that acute global brain ischemia 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 mouse 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 provide protection of Fructus Corni extract to chmice acute global brain ischemia 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 time length continuously with stopwatch record mouse, 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 mouse, shows that Fructus Corni extract has the effect that energy metabolism that the antagonism cerebral ischemia/anoxia causes reduces the neural cell injury that causes.
Table 2. cornel extractive affects group number of animals mouth breathing time (second) control group 10 25.34 ± 2.58 Nimodipines (positive control drug) 14 28.66 ± 1.22**CTG 0.75g/kg 12 27.02 ± 2.27*CTG 1.5g/kg 13 27.62 ± 2.00*CTG 3.0g/kg 11 31.44 ± 6.42** to what the disconnected cranium of mouse caused mouth breathing time behind the acute brain damage following complete
M ± SD; * p<0.05, * * p<0.01 is compared with control group Experimental example 3Fructus Corni extract is to the influence of photochemical induction acute cerebral infarction mouse model
Experiment purpose: increased by oxyradical and to cause vascular endothelial cell damage, platelet aggregation forms thrombus, and causing the local organization ischemic necrosis is the common pathological change of ischemic angiocardiopathy and cerebrovascular disease and peripheral angiopathy.The modeling principle of photochemical induction acute cerebral infarction is that photoactive substance (rose-red) is injected mouse tail vein, cold light source irradiation mouse cranium portion with the 560nm wavelength, photochemical reaction takes place, generate a large amount of oxyradicals, cause vascular endothelial cell damage, platelet aggregation forms thrombus in irradiated region, local cortex ischemic necrosis.This research is intended to observe the influence of Fructus Corni extract to acute cerebral infarction mouse model cerebrovascular trauma and ischemic half dark space.
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 mouse 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 make homogenate, and with the optical density(OD) of the average cerebral tissue of colorimetric method for determining.The infraction severe patient, dyeing is dark, and optical density(OD) is big, and ischemic half dark space area is big.
Experimental result: gavage the optical density(OD) that Fructus Corni extract can reduce photochemical induction acute cerebral infarction model mice cerebral tissue Yi Wensilan, and reduce the area (table 3) of model mice ischemic half dark space.Showing that Fructus Corni extract can alleviate owing to oxyradical 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. cornel extractive affects group number of animals Yi Wensilan (OD value) ischemic half blanking bar Area Model group 6 0.1333 ± 0.0759 to photochemical induction cerebral infarction mouse model ++ ++ hydergine (positive control drug) 7 0.1121 ± 0.0441+CTG 0.167g/kg 6 0.1097 ± 0.0259 ++ CTG 0.5g/kg 8 0.1072 ± 0.0303+CTG 1.5g/kg 8 0.0547 ± 0.0260*+
M ± SD; * p<0.05 is compared with model group
Ischemic half blanking bar :+, ++, +++, ++ ++ represent area ascending successively. Embodiment 4Fructus Corni extract causes the influence of focal cerebral ischemia rat model to middle cerebral artery occlusion
Experiment purpose: it is the common pathological change of ischemic angiocardiopathy and cerebrovascular disease and peripheral angiopathy that the concentration of cytoplasm calcium ion that is caused by ischemic increases unusually, and calcium ion increases also can cause vasoconstriction or spasm.Middle cerebral artery occlusion (MCAO) is the focal cerebral ischemia model of the simulation clinical disease used always.The imbalance of intracellular calcium stable state plays an important role in the cell ischemic damage.The concentration of cytoplasm calcium ion that is caused by ischemic increases unusually, can make the Phospholipid hydrolase that is subjected to regulation of calcium, proteolytic enzyme, 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 ischemic after the influence of calcium ion concn in the endochylema.
Experimental technique:
(1) Modelling: experimental rat is in administration in the 14th day row intraperitoneal anesthesia after 30 minutes, the diagonal otch about in the of one in right external auditory canal and right outer canthus line mid point work, be separated to abundant exposure arteria cerebri media, be affixed on arteria cerebri media and anterior cerebral veins infall with the filter paper bar that is soaked with 50% iron trichloride, really block with the microscopic examination blood flow of middle cerebral artery after 30 minutes, 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 thickness in the optic chiasma level.Add artificial cerebrospinal fluid 400 microlitres that contain 5uMFluo-3/AM, hatch laser confocal microscope mensuration hippocampus intracellular calcium fluorescence intensity after 1 hour.
Experimental result: every group of right side is the ischemic side, and calcium ion concn increases than strong side (left side).Left and right sides brain calcium ion concn difference compares, and the interior calcium ion fluorescence intensity of model group hippocampal cell increases obvious than control group, and model is set up.Fructus Corni extract medication group reduces (table 4) than calcium ion concn in the model group hippocampal cell.The effect that this compound reduces calcium ion concn in the endochylema helps protecting ischemic tissue, improves cell survival rate, and helps vasodilation, and is significant to the control of ischemic vascular disease.
Table 4 Fructus Corni extract influences group number of animals calcium ion fluorescence intensity difference to calcium ion concn in the MCAO rat model hippocampal cell
The ischemic side is good for side (ischemic side-strong side) difference control group 6 47.99 ± 26.28 36.72 ± 6.93 11.27 ± 22.38* model group, 6 105.2741.30 60.31 ± 32.34 44.96 ± 12.44 hydergines, 4 86.0235.10 56.1527.30,29.88 ± 29.13CTG 0.33g/kg, 4 99.2013.52 58.33 ± 19.10 40.86 ± 18.23CTG 1g/kg 6 89.57 ± 15.67 54.57 ± 17.75 34.60 ± 3.92CTG 3g/kg 6 95.22 ± 29.42 64.40 ± 23.44 30.82 ± 17.39
M ± SD; * p<0.05 is compared with control group Experimental example 5Fructus Corni extract is to the influence of bilateral ligation rat model learning and memory function
Experiment purpose: the result of histoorgan ischemic 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.
Experimental technique: the preparation of bilateral ligation rat model and grouping 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 enter the darkroom and shocked by electricity 2 times, test after 24 hours, the record rat enters the number of times and the latent period in darkroom, and classification.Two forelimbs enter the darkroom and are designated as 1 fen; Three forelimbs enter the darkroom and are designated as 2 fens; Four limbs enter 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 number of times (mistake number) that the each training and testing of rat all writes down the time (time of arrival) of reaching home and enters cecum.As school grade, 4 time of arrival cecum testing period and wrong number be as the memory achievement with the average of 4 cecum time of arrival training period and wrong number, 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, go into the position, pond by platform institute 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: the method for the long-term ligation of bilateral common carotid arteries can make rat produce learning memory disorder, Fructus Corni extract can improve the learning and memory of rat through long-time medication, shows the time of swimming out of and the distance that can shorten in the water maze test, reduces errors number (table 5-7); In keeping away dark test, can prolong latent period, reduce errors number (table 8).Show that Fructus Corni extract can improve the dysfunction that long-term histoorgan ischemic causes.Table 5. Fructus Corni extract is swum out of the time influence of (second) to bilateral ligation rat model Morris water maze
Group example several second day the 3rd day the 4th day
Normal control 14 25.78 ± 23.36 12.82 ± 15.22*, 9.50 ± 5.73*
Model 12 46.38 ± 34.56 35.36 ± 24.17 25.75 ± 20.20
CTG 3g/kg 9 32.85±22.56 10.52±7.04** 16.55±10.98
M ± SD compares 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
Group example several second day the 3rd day the 4th day
Normal control 14 532.51 ± 485.17 307.46 ± 382.49*, 190.06 ± 108.84*
Model 12 934.25 ± 759.87 746.41 ± 540.72 612.66 ± 505.56
CTG 3g/kg 9 10.44±457.20 227.11±134.18* 366.78±251.87
M ± SD compares 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
Group school grade (4 cecum) memory achievement (4 cecum)
Swimming time (s) errors number swimming time (s) errors number
Normal 59.4316.19 1.19 ± 0.61** 28.64 ± 20.55** 0.39 ± 0.77*
Model 74.41 ± 31.02 2.92 ± 1.83 66.33 ± 28.85 1.83 ± 2.02
CTG(3g/kg) 63.22±36.83 2.78±2.38 35.33±24.47* 0.61±0.82*
M ± SD compares 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
The errors number classification of group example number latent period (second)
Normal control 14 234.64 ± 20.04* 0.07 ± 0.27* 0.07 ± 0.27*
Model 12 169.75 ± 99.34 0.92 ± 1.31 1.17 ± 1.59
CTG 3g/kg 9 211.25±58.42 0.25±0.46 0.38±0.74
M ± SD compares with model group: * P<0.05, * * P<0.01 Experimental example 6Fructus Corni extract is to the influence of bilateral ligation rat model pallium acetylcholine esterase active
Experiment purpose: acetylcholinesterase (AchE) is the enzyme of hydrolysis neurotransmitter acetylcholine in the brain.The AchE inhibitor can slow down the katabolism of vagusstoff, improves ability of learning and memory.This research is observed Fructus Corni extract to the active influence of the AchE of rat cerebral tissue.
Experimental technique: after rat cerebral cortex homogenate is centrifugal, gets supernatant liquor and measure the AchE activity with biochemical method.
Experimental result: Fructus Corni extract can obviously suppress bilateral ligation rat model pallium AchE activity (table 9).
Table 9. Fructus Corni extract is to the active influence of bilateral ligation rat model pallium AchE
Group example number AchE (umol/mg albumen)
Normal control 12 0.430 ± 0.073*
Model 8 0.623 ± 0.189
CTG 3g/kg 6 0.329±0.077**
M ± SD compares with model group: * P<0.05, * * P<0.01 Experimental example 7Fructus Corni extract is to the active influence of bilateral ligation rat model pallium monoamine oxidase-B
Experiment purpose: monoamine oxidase extensively is distributed in animal tissues, mainly is positioned at the cell mitochondrial part, but the various monoamines 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.Monoamine oxidase-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 Parkinson's disease, senile dementia and delays senility in recent years.This research is observed Fructus Corni extract to the active influence of bilateral ligation rat model pallium MAO-B.
Experimental technique: after big rat brain tissue homogenate is centrifugal, gets supernatant liquor and measure the MAO-B activity with biochemical method.
Experimental result: Fructus Corni extract can obviously suppress bilateral ligation rat model pallium MAO-B activity (table 10).
Table 10. Fructus Corni extract is to the active influence of bilateral ligation rat model pallium MAOB
Group example number MAO-B (U/mg/h)
Normal control 12 899.2 ± 190.4*
Model 8 1214.0 ± 230.1
CTG 3g/kg 6 851.3263.5*
M ± SD compares with model group: * P<0.05
In sum, from skunk bush, extract the total glycoside compound that obtains, can obviously reduce platelet aggregation by ADP and thrombin induction, alleviate acute cerebral infarction animal model blood vessel injury, reduce ischemic half dark space area, reduce intracellular calcium concentration, improve energy and substance metabolism after the acute global brain ischemia anoxic, improve ability of learning and memory, acetylcholine esterase inhibition and the monoamine oxidase-B activity of long-term cerebral ischemia animal model.Show that this compound 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 organ local circulation and dysfunction.Be mainly used in treatment arteriosclerosis, ischemic angiocardiopathy and cerebrovascular disease and peripheral angiopathy etc. clinically.
Preferred forms Embodiment 1The preparation of Fructus Corni extract
Skunk bush medicinal 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, refrigerate standby; Get spissated skunk bush water extraction, last HP20 macroporous adsorptive resins makes soup flow through full post, carries out gradient elution with deionized water, 30%, 50% ethanol successively, collects 50% alcoholic acid elutriant, and concentrating under reduced pressure becomes medicinal extract; With the isolating total glycoside extract alcohol extraction of macroporous adsorbent resin, remove organic solvent, concentrate, drying obtains solid product.Yield 9.1%. Embodiment 2The preparation of Fructus Corni extract
Skunk bush medicinal 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%, refrigerate 24 hours, and filtration behind the decompression filtrate recycling ethanol, refrigerates standby.
Get above-mentioned skunk bush water extract-alcohol precipitation extracting solution, last HP20 macroporous adsorptive resins makes soup flow through full post, carries out gradient elution with deionized water, 30%, 50% ethanol successively, collects 50% alcoholic acid elutriant, and concentrating under reduced pressure becomes medicinal extract.
With the isolating total glycoside extract alcohol extraction of macroporous adsorbent resin, remove organic solvent, concentrate, drying obtains solid product.Yield 8.1%.
Through the high performance liquid chromatograph analysis, cornin, morroniside, Methylmorroniside, Ma Qiansu (being loganin), dehydrogenation Ma Qiansu, iridoid glycoside, sweroside, saponin(e equal size account for 72% of Fructus Corni extract in the described product.

Claims (9)

1, a kind of Fructus Corni extract is characterized in that it is to extract with following method to obtain:
Skunk bush medicinal material water decocts 2-4 time, and amount of water 3-10 times, decocting time 1-4 hour, merge decoction liquor, filter the back concentrating under reduced pressure, refrigerate standby;
With macroporous adsorptive resins on the above-mentioned spissated skunk bush aqueous extract, make soup flow through full post, carry out gradient elution with deionized water, 10%-95% ethanol successively, concentrating under reduced pressure becomes medicinal extract;
The isolating total glycoside extract of macroporous adsorbent resin is made with extra care with organic solvents such as ethyl acetate or ethanol, got effective part extract.
2, Fructus Corni extract according to claim 1 is characterized in that it is to extract with following method to obtain:
Skunk bush medicinal material water decocts 2-4 time, amount of water 3-10 doubly, time 1-4 hour, merge decoction liquor, filter the back concentrating under reduced pressure, adding ethanol, to transfer to determining alcohol be 50%-90%, refrigerate 12-48 hour, filtration behind the decompression filtrate recycling ethanol, refrigerates standby;
With macroporous adsorptive resins on the above-mentioned skunk bush water extract-alcohol precipitation extracting solution, make soup flow through full post, carry out gradient elution with deionized water, 10%-95% ethanol successively, concentrating under reduced pressure becomes medicinal extract; Or, reclaiming propyl carbinol with n-butanol extraction 3-5 time of above-mentioned water extract-alcohol precipitation extracting solution, the extraction liquid concentrating under reduced pressure becomes medicinal extract;
The isolating total glycoside extract of macroporous adsorbent resin is made with extra care with organic solvents such as ethyl acetate or ethanol, got effective part extract.
3,, it is characterized in that it is is the extract of main active ingredient with the Fructus Corni total glycosides according to the described Fructus Corni extract of claim 1.
4, according to the extract of claim 3, wherein said Fructus Corni total glycosides comprises cornin, morroniside, Methylmorroniside, Ma Qiansu, dehydrogenation Ma Qiansu, iridoid glycoside, sweroside, saponin(e.
5, the application of Fructus Corni extract in preparation control ischemic vascular disease medicine.
6, purposes according to claim 5 is characterized in that said ischemic vascular disease is meant vasospasm, thrombosis or vascular occlusion that artery and vein systemic disease damage causes, the organ local circulation or the dysfunction that are perhaps caused.
7, purposes according to claim 5 is characterized in that said ischemic vascular disease is meant any in arteriosclerosis, transient ischemic attack or histoorgan infraction or the surrounding blood vessel obturation.
8, purposes according to claim 5, the pathomechanism that it is characterized in that said ischemic vascular disease show as vasospasm or luminal stenosis due to a variety of causes, blood vessel endothelium injury, platelet aggregation increases, thrombosis, or embolus obstruction cause tissue ischemia so that downright bad.
9, Fructus Corni extract has application in the medicine of following arbitrary pharmacological action in preparation, and wherein said pharmacological action comprises anticoagulant, alleviates the acute cerebral infarction blood vessel injury, reduces to block ischemic half dark space area; Reduce intracellular calcium concentration, improve energy and substance metabolism after the acute global brain ischemia anoxic, improve ability of learning and memory, acetylcholine esterase inhibition and monoamine oxidase-B activity.
CN 02159502 2002-12-30 2002-12-30 Extracts of cornus officinalis and its preparation and use Pending CN1424319A (en)

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CN 02159502 CN1424319A (en) 2002-12-30 2002-12-30 Extracts of cornus officinalis and its preparation and use
CNB2003101103168A CN100364545C (en) 2002-12-30 2003-12-30 Dogwood fruit extract and its preparing method and use
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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WO2005003145A1 (en) * 2003-07-03 2005-01-13 Hutchison Medipharma Enterprises Limited Shanzhuyu extract and uses thereof
CN100364545C (en) * 2002-12-30 2008-01-30 首都医科大学宣武医院 Dogwood fruit extract and its preparing method and use
CN100435810C (en) * 2005-08-15 2008-11-26 江苏吴中苏药医药开发有限责任公司 Dogwood fruit extract and its preparation process
CN1565467B (en) * 2003-06-17 2010-05-12 成都地奥制药集团有限公司 Use of cornel and its extract in preparation alpha-glucosidase inhibitor medicine
CN102477053A (en) * 2010-11-25 2012-05-30 苏州宝泽堂医药科技有限公司 Method for extracting morroniside and loganin from Macrocarpium officinalis
CN103360443A (en) * 2013-07-30 2013-10-23 天津科丝美特生物科技有限公司 Method for extraction and purification of four iridoid glycosides in cornus officinalis
CN104523809A (en) * 2014-12-09 2015-04-22 河南中医学院 Preparation method of common macrocarpium fruit pigment
CN107929347A (en) * 2017-12-25 2018-04-20 浙江工业大学 Application of the Fructus Corni total glycosides in the medicine for preparing prevention remodeling ventricle
CN112047984A (en) * 2019-06-06 2020-12-08 南京宸翔医药研究有限责任公司 Extraction, separation and purification method of various components of dogwood

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CN100364545C (en) * 2002-12-30 2008-01-30 首都医科大学宣武医院 Dogwood fruit extract and its preparing method and use
CN1565467B (en) * 2003-06-17 2010-05-12 成都地奥制药集团有限公司 Use of cornel and its extract in preparation alpha-glucosidase inhibitor medicine
WO2005003145A1 (en) * 2003-07-03 2005-01-13 Hutchison Medipharma Enterprises Limited Shanzhuyu extract and uses thereof
CN100435810C (en) * 2005-08-15 2008-11-26 江苏吴中苏药医药开发有限责任公司 Dogwood fruit extract and its preparation process
CN102477053A (en) * 2010-11-25 2012-05-30 苏州宝泽堂医药科技有限公司 Method for extracting morroniside and loganin from Macrocarpium officinalis
CN103360443A (en) * 2013-07-30 2013-10-23 天津科丝美特生物科技有限公司 Method for extraction and purification of four iridoid glycosides in cornus officinalis
CN104523809A (en) * 2014-12-09 2015-04-22 河南中医学院 Preparation method of common macrocarpium fruit pigment
CN104523809B (en) * 2014-12-09 2018-08-07 河南中医学院 A kind of preparation method of Fructus Corni pigment
CN107929347A (en) * 2017-12-25 2018-04-20 浙江工业大学 Application of the Fructus Corni total glycosides in the medicine for preparing prevention remodeling ventricle
CN112047984A (en) * 2019-06-06 2020-12-08 南京宸翔医药研究有限责任公司 Extraction, separation and purification method of various components of dogwood

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