CN101284050B - Corydalis tuber water soluble part medicament and its preparation method and application - Google Patents
Corydalis tuber water soluble part medicament and its preparation method and application Download PDFInfo
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Abstract
The invention relates to a pharmaceutical prepared from corydalis tuber water-soluble parts and a preparation method thereof. The preparation method comprises pulverizing corydalis tuber material into coarse powder; extracting with 80% ethanol under heating and refluxing for three times and four hours each time; mixing the extraction solutions; recovering and concentrating until the relative density reaches 1.02-1.06 (50DEG C) to obtain corydalis tuber extract; adsorbing with a macroporous resin column; eluting with water of 6-8 times the volume of the column; collecting the water eluant; recovering water; and drying. The invention also relates to the application of the pharmaceutical on treating cardiovascular diseases, particularly preparing pharmaceuticals for treating coronary heart disease, angina pectoris and acute myocardial infarction.
Description
(1) technical field:
The present invention relates generally to the corydalis tuber water soluble part medicament and the preparation method of the dry tuber preparation of Rhizoma Corydalis (Corydalis YanhusuoW.T.Wang); Also relate to the purposes of this corydalis tuber water soluble part medicament in the treatment cardiovascular disease.
(2) background technology:
Cardiovascular disease such as coronary heart disease, angina pectoris is serious harm human life and healthy commonly encountered diseases, according to World Health Organization (WHO), has 1 and die from coronary heart disease in the people of per 3 death of the U.S., has every year more than 50 ten thousand people to die from myocardial infarction.In China, the sickness rate of cardiovascular disease is example also in continuous rising with coronary heart disease, and sickness rate is about 2.5%, and 1,500,000 New Development patients are arranged every year, and its mortality rate has increased 2-3 doubly in the period of 10.Along with the raising of China's modernization of industry degree, the quickening of rhythm of life, the change of diet structure and living habit, cardiovascular disease incidence rates such as coronary heart disease, angina pectoris also will constantly rise.
Rhizoma Corydalis have invigorate blood circulation, regulate the flow of vital energy, effect such as pain relieving, existing result of study and document are thought, alkaloid is its active site in the Rhizoma Corydalis extract, these known organism alkali such as dehydrogenation Rhizoma Corydalis, tetrahydropalmatine, protopine are effective ingredient in the alkaloid, and the monograph of Rhizoma Corydalis, document think that mostly the quaternary ammonium base of dehydrocorydaline one class is the active ingredient of treatment myocardial infarction.Research viewpoint before the present invention has changed, the Rhizoma Corydalis alkaloid is not the active site that has best cardiovascular effect in the Rhizoma Corydalis, new discovery safer, more effective active site, i.e. a corydalis tuber water soluble part medicament.Characteristics of the present invention, all alkaloids such as dehydrocorydaline, tetrahydropalmatine, protopine have been removed, significantly reduced toxicity, improved the safety of medicine, another characteristics of the present invention, the corydalis tuber water soluble part medicament of preparation, the cardiovascular effect has obtained further reinforcement, compare with Rhizoma Corydalis, Rhizoma Corydalis alkaloid, significantly improved the cardiovascular effect of Rhizoma Corydalis extract.
The present invention is different with the Kedaling sheet, the Kedaling sheet is to use 80% alcohol reflux, its effective ingredient is alkaloids such as dehydrocorydaline, tetrahydropalmatine, alkaloid is its effective ingredient, the present invention has removed all Rhizoma Corydalis alkaloids, has invented the new active site of Rhizoma Corydalis, and the cardiovascular effect at this position is stronger than Rhizoma Corydalis alkaloid in the Rhizoma Corydalis extract, give the mice maximum tolerated dose, also do not find toxicity.
The present invention is different with patent " polysaccharide of rhizoma corydalis, production method and purposes " CN1660914A, and the present invention passes through the water soluble part that obtains after macroporous resin separates for Rhizoma Corydalis extract, and CN1660914A is a polysaccharide of rhizoma corydalis, and the two material base is different.
The present invention is different with patent " dripping pills of corydalis tuber and preparation thereof " CN1730026A, and extraction process of the present invention is different fully with the technology of CN1730026A, and active site is also different.Through toxicity test relatively, corydalis tuber water soluble part medicament safety of the present invention is greatly improved.
The present invention extracts the corydalis tuber water soluble part medicament that obtains from corydalis tuber medicinal material, changed this result of study and traditional view before, be expected to obtain safer, effectively have the new drug of cardiovascular effect, this is the great achievement that realizes in the modernization of Chinese medicine process.
(3) summary of the invention:
Task of the present invention provides corydalis tuber water soluble part medicament and its production and use.
Technical scheme of the present invention is:
A kind of preparation method of corydalis tuber water soluble part medicament,
1) be raw material with Rhizoma Corydalis (Corydalis Yanhusuo W.T.Wang) tuber, be ground into coarse powder, be about the 10-30 order, extract three times with 6 times of amount 80% alcohol heating reflux, each 4 hours, merge three times extracting solution, reclaim and be concentrated into relative density 1.02-1.06 (50 ℃), obtain the Rhizoma Corydalis extracting solution;
2) the Rhizoma Corydalis extracting solution adsorbs through macroporous resin column, and the amount of macroporous resin is 3-6 a times of Rhizoma Corydalis extracting solution weight;
3) then with the water elution of 6-8 times of column volume, collect water elution liquid, merge water elution liquid, obtain corydalis tuber water soluble part medicament, yield 6%～8%, wherein the Main Ingredients and Appearance general flavone content is greater than 15%.
Described macroporous resin is selected among D201, D101, AB-8, the X-5 any, and resin column bed blade diameter length ratio is 1: 4.
In macroporous resin column purifies and separates process, the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column; All enter resin bed to extracting solution, static 1 hour, allow it fully adsorb.
In the water eluting macroporous resin column process, water velocity 1BV/h.
The corydalis tuber water soluble part medicament of preparation method preparation of the present invention is used to prepare the purposes for the treatment of cardiovascular disease medicine, and according to the present invention, term " cardiovascular disease " is meant for example diseases such as coronary heart disease, angina pectoris, acute myocardial infarction.
The corydalis tuber water soluble part medicament of the inventive method preparation, add a certain proportion of conventional pharmaceutic adjuvant, the preparation formulation of making can be selected from any in capsule, tablet, drop pill, the oral liquid, and the dosage of corydalis tuber water soluble part medicament is 200-300mg in the preparation.
The corydalis tuber water soluble part medicament yield that preparation method of the present invention obtains is 6%～8%, and main component is a flavones ingredient, adopts determined by ultraviolet spectrophotometry, and general flavone content is greater than 15%.
The present invention compared with prior art has outstanding characteristics and obvious improvement.
The present invention is raw material with the corydalis tuber medicinal material, and Rhizoma Corydalis (Corydalis Yanhusuo W.T.Wang) is a herbaceos perennial, and underground tuber is a medicinal part, is distributed in ground such as Zhejiang, Jiangsu, Shandong, Hebei.
The inventor finds that through research is unexpected the corydalis tuber water soluble part medicament of the inventive method preparation, general flavone content are greater than 15%, and good stability is fit to the preparation medicine, is used for the treatment of cardiovascular disease.Beneficial effect of the present invention mainly contains: (1) provides the method for corydalis tuber water soluble part medicament; (2) remove toxic component, improved drug safety; (3) the inventive method advanced design, reasonable, stable, easy to operate has stronger practicality; (4) be expected to obtain safer, effectively have a new drug of cardiovascular disease preventive and therapeutic effect.
(4) specific embodiments:
The following examples are used to further specify and describe the present invention, but and do not mean that the present invention only limits to this.
Embodiment 1:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, each 4 hours, merge three times extracting solution, reclaim and be concentrated into relative density 1.04 (50 ℃), obtain the Rhizoma Corydalis extracting solution;
The Rhizoma Corydalis extracting solution is 3kg macroporous resin D201 post absorption through weight, and resin column bed blade diameter length ratio is 1: 4, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column, all enters resin bed to extracting solution, static 1 hour, allows it fully adsorb; With 6 times of column volume water elutions, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, and concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 6.54%; Adopt determined by ultraviolet spectrophotometry, total flavones 16.5%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of conventional pharmaceutic adjuvant, makes capsule, specification, and every contains corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular disease.
Embodiment 2:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, merge three times extracting solution, reclaim and be concentrated into relative density 1.02 (50 ℃), obtain the Rhizoma Corydalis extracting solution.
The Rhizoma Corydalis extracting solution is the absorption of 4kg macroporous resin D201 post through weight, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column; All enter resin bed to extracting solution, static 1 hour, allow it fully adsorb; With the water elution of 8 times of amount column volumes, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 7.83% adopts determined by ultraviolet spectrophotometry, total flavones 15.8%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of conventional pharmaceutic adjuvant, makes tablet, specification, and every contains corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular disease.
Embodiment 3:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, merge three times extracting solution, reclaim and be concentrated into relative density 1.06 (50 ℃), obtain the Rhizoma Corydalis extracting solution.
The Rhizoma Corydalis extracting solution is through 6kg macroporous resin D101 post absorption, and resin column bed blade diameter length ratio is 1: 4, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column, all enters resin bed to extracting solution, static 1 hour, allows it fully adsorb; With the water elution of 7 times of amount column volumes, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 6.97% adopts determined by ultraviolet spectrophotometry, and total flavones is 15.6%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of conventional pharmaceutic adjuvant, makes oral liquid, and specification is taken at every turn and contained corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular disease.
Embodiment 4:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, merge three times extracting solution, reclaim and be concentrated into relative density 1.05 (50 ℃), obtain the Rhizoma Corydalis extracting solution.
The Rhizoma Corydalis extracting solution is through 5kg macroporous resin D101 post absorption, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column, all enters resin bed to extracting solution, static 1 hour, allows it fully adsorb; With the water elution of 8 times of column volumes, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 7.92% adopts determined by ultraviolet spectrophotometry, and total flavones is 15.8%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of conventional pharmaceutic adjuvant, makes capsule, specification, and every contains corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular.
Embodiment 5:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, merge three times extracting solution, reclaim and be concentrated into relative density 1.03 (50 ℃), obtain the Rhizoma Corydalis extracting solution.
The Rhizoma Corydalis extracting solution is the macroporous resin AB-8 post absorption of 4kg through weight, and resin column bed blade diameter length ratio is 1: 4, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column, all enters resin bed to extracting solution, static 1 hour, allows it fully adsorb; With the water elution of 6 times of column volumes, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 6.16% adopts determined by ultraviolet spectrophotometry, and total flavones is 15.9%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of conventional pharmaceutic adjuvant, makes drop pill, specification, and each dose contains corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular.
Embodiment 6:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, merge three times extracting solution, reclaim and be concentrated into relative density 1.06 (50 ℃), obtain the Rhizoma Corydalis extracting solution.
The Rhizoma Corydalis extracting solution is through the macroporous resin AB-8 of 6kg post absorption, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column, all enters resin bed to extracting solution, static 1 hour, allows it fully adsorb; With the water elution of 8 times of column volumes, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 6.99% adopts determined by ultraviolet spectrophotometry, and total flavones is 16.4%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of conventional pharmaceutic adjuvant, makes oral liquid, and specification is taken at every turn and contained corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular.
Embodiment 7:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, merge three times extracting solution, reclaim and be concentrated into relative density 1.02 (50 ℃), obtain the Rhizoma Corydalis extracting solution.
The Rhizoma Corydalis extracting solution is through the macroporous resin X-5 of 5kg weight post absorption, and resin column bed blade diameter length ratio is 1: 4, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column, all enters resin bed to extracting solution, static 1 hour, allows it fully adsorb; With the water elution of 7 times of column volumes, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 7.13% adopts determined by ultraviolet spectrophotometry, and general flavone content is 15.7%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of conventional pharmaceutic adjuvant, makes capsule, specification, and every contains corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular.
Embodiment 8:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, merge three times extracting solution, reclaim and be concentrated into relative density 1.05 (50 ℃), obtain the Rhizoma Corydalis extracting solution.
The Rhizoma Corydalis extracting solution is through the macroporous resin X-5 of 3.8kg weight post absorption, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column, all enters resin bed to extracting solution, static 1 hour, allows it fully adsorb; With the water elution of 6 times of column volumes, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 7.02% adopts determined by ultraviolet spectrophotometry, and general flavone content is 15.6%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of diluent, makes tablet, specification, and every contains corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular.
Embodiment 9:
Get corydalis tuber medicinal material 1000g, be ground into coarse powder, add 80% ethanol 6000ml heating and refluxing extraction three times, merge three times extracting solution, reclaim and be concentrated into relative density 1.04 (50 ℃), obtain the Rhizoma Corydalis extracting solution.
The Rhizoma Corydalis extracting solution is through the macroporous resin X-5 of 6kg weight post absorption, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column, all enters resin bed to extracting solution, static 1 hour, allows it fully adsorb; With the water elution of 8 times of column volumes, eluting water velocity 1BV/h collects water elution liquid, merges water elution liquid, concentrated, drying under reduced pressure (70 ℃) are ground into fine powder, obtain corydalis tuber water soluble part medicament, yield 7.83% adopts determined by ultraviolet spectrophotometry, and general flavone content is 15.9%.
Rhizoma Corydalis Rhizoma Corydalis water soluble part medicament adds a certain amount of conventional pharmaceutic adjuvant, makes oral liquid, and specification is taken at every turn and contained corydalis tuber water soluble part medicament 200-300mg, promptly gets the pharmaceutical preparation with the effect of treatment cardiovascular.
Embodiment 10:
Pharmacodynamics test 1 instrument of the cardiovascular protection effect of corydalis tuber water soluble part medicament: the ALC-V8 animal respirator, ALC-MPA multiple tracks bio signal analytical system, Alcott Bioisystech Co., Ltd in Shanghai makes; Image analysis system, Jetta Science and Technology Ltd. in Jiangsu provides.Glacial acetic acid, the generous chemical reagent in Hangzhou factory, lot number: 20040907; Chlorination nitro blue tetrazolium (NBT), advance chemical chemical reagent work of China produces lot number: 20040602; Pentobarbital sodium, Chinese Medicine Shanghai chemical reagent company limited is produced, lot number: 20030816; Reason saline, Shapuaisi Pharmaceutical Co., Ltd., Pinghu City, Zhejiang Prov. produces, lot number: 040711.
2 methods
2.1 corydalis tuber water soluble part medicament Chinese People's Anti-Japanese Military and Political College Mus myocardial ischemia test
2.1.1 to the influence of rat heart muscle infarct size, to the influence of the Electrocardiographic influence of Rat of Myocardial Infarction, rat heart rate
Get the SD rat, male, body weight 160-180g, be divided into following each group at random, every group 8, model control group, 051901 group (corydalis tuber water soluble part medicament), 061129 group (Rhizoma Corydalis ethanol extraction), 061130 group (Rhizoma Corydalis total alkaloids), diltiazem hydrochloride positive controls (dosage sees Table 1).Give the 2ml normal saline after the model group modeling.The above-mentioned reagent thing that is subjected to is all in operation back 2min gastric infusion.Concrete experimental procedure: get the SD rat, 1% pentobarbital sodium 40mg/kg (ip) anesthesia, it is fixing to lie on the back, the record II ECG that leads, the sterilization skin of chest, 2 centimetres longitudinal incision is made in the breastbone left side, the passivity separating muscle, pedestrian worker breathes (respiratory quotient 1: 2, respiratory frequency 53 times/minute, ventilation 0.25～0.49ml/min), open breast, cut off pericardium, gently press the thorax right side, extrude heart, ligation arteria coronaria left anterior descending branch between arterial cone and left auricle, (change according to the color below the heart ligation position and electrocardiogram judge myocardial ischemia) closes breast, surveys the II ECG that leads.Each group operation back 2min gastric infusion.Performed the operation back 4 hours, and cored, 4 ℃ of normal saline flushings are cut into the thin slice of 0.1cm left and right thickness with the following heart in ligation position, place 37 ℃ of 0.1%NBT 10min that dyes, and calculate infarcted region and non-infarcted region area with image analysis software.Observe the II ECG ST section of leading and raise degree and changes in heart rate.
2.2 corydalis tuber water soluble part medicament influences the mice analgesic
2.2.1 acetic acid twisting method analgesic experiment
Get mice, be divided into following each group at random, 10 every group, male and female half and half.Model control group, 051901 group (corydalis tuber water soluble part medicament), 061129 group (Rhizoma Corydalis ethanol extraction), 061130 group (Rhizoma Corydalis total alkaloids), aspirin positive controls, indometacin (dosage sees Table 2).The administration group is irritated stomach respectively and is tried thing, successive administration 3 days.30min after the last administration, the equal lumbar injection 0.6% glacial acetic acid solution 0.2ml/ of each mice only observe the time that writhing response occurs, calculate incubation period, and turn round the body number of times in the record 15min, to the experimental result statistical analysis.
2.2.2 hot plate method analgesic experiment
The temperature of regulating metallic plate is 55 ± 0.5 ℃, gets 1 of female mice at every turn, is placed on the metallic plate, and the metapedes required time appears licking in the record mice, as the pain threshold of this mice, licks the person that do not occur licking the metapedes in metapedes or the 30s in all 5s, gives it up.Survey the threshold of pain before the experiment again 1 time, with the meansigma methods of the twice threshold of pain pain threshold before as this Mus administration.The blank group gives N.S, and the administration group is irritated stomach respectively and tried thing and positive control drug aspirin.30min after the administration, mice places on 55 ℃ of (± 0.5 ℃) constant temperature hot plates, and be the threshold of pain index incubation period of licking the metapedes reaction with mice, and be 60S deadline.After the administration 10,30,60,120min measures the pain threshold of mice, with before the administration and matched group relatively.If mice is 60s analgesia still on hot plate, take out immediately, press 60s calculating.
3. result
3.1 corydalis tuber water soluble part medicament Chinese People's Anti-Japanese Military and Political College Mus myocardial ischemia test
3.1.1 influence to the rat heart muscle infarct size
The results are shown in Table one.
Table one corydalis tuber water soluble part medicament is to the influence of rat heart muscle infarct size (n=8, X ± SD)
Compare with model group,
*P＜0.05;
*P＜0.01; Significant difference is arranged
3.1.2 corydalis tuber water soluble part medicament is to the Electrocardiographic influence of heart infarction rat
The results are shown in Table two.
Table two corydalis tuber water soluble part medicament is raised influence (n=8, the X ± SD) of degree to heart infarction rat ECG ST section
Compare with model group,
*P＜0.05;
*P＜0.01; Significant difference is arranged
3.1.3 corydalis tuber water soluble part medicament is to the influence of rat heart rate
The results are shown in Table three.
Table three corydalis tuber water soluble part medicament is to the influence of heart infarction rat heart rate (n=8, X ± SD)
Compare with model group,
*P＜0.05;
*There is significant difference P＜0.01
3.2 corydalis tuber water soluble part medicament influences the mice analgesic
3.2.1 corydalis tuber water soluble part medicament the results are shown in Table four to mice acetic acid twisting method analgesic experiment.
Table four acetic acid twisting method analgesic experiment result
Compare with the normal saline group,
*P＜0.05,
*P＜0.01,
* *P＜0.001
3.2.2 corydalis tuber water soluble part medicament the results are shown in Table five to mice hot plate method experiment of analgesic.
The influence of table five pair mice hot plate method analgesic activity (x ± s)
Compare with matched group,
*P＜0.05,
*P＜0.01
The result:
Animal experiment shows: corydalis tuber water soluble part medicament (051901 group), Rhizoma Corydalis ethanol extraction (061129 group) all can significantly reduce the rat heart muscle infarct size with Rhizoma Corydalis total alkaloids (061130 group), can significantly reduce the degree that myocardial infarction rat ST section is raised, keep normal cardiac rate, the pain threshold of mice can be significantly improved, the pain that mice causes because of injection acetic acid can be significantly alleviated thermostimulation.
Conclusion:
From the above test of pesticide effectiveness relatively, corydalis tuber water soluble part medicament (051901 group) is strong with Rhizoma Corydalis total alkaloids (061130 group) effect than Rhizoma Corydalis ethanol extraction (061129 group) in its drug effect of cardiovascular drug efficacious prescriptions face.Thereby be the drug effect new discovery of present corydalis tuber water soluble part.
Embodiment 11:
The anxious poison test of corydalis tuber water soluble part medicament
1. experiment material
1.1. animal: ICR mice, body weight 18～22g, 24, male and female half and half
1.2. medicine:
1) corydalis tuber water soluble part medicament (051901 group)
2) Rhizoma Corydalis ethanol extraction (061129 group)
3) Rhizoma Corydalis total alkaloids (061130 group)
2. equipment: irrigation stomach device, beaker, syringe
3. experimental technique
According to death condition of animal in the analgesic experiment and dosage at that time, being tried thing corydalis tuber water soluble part medicament (051901 group), Rhizoma Corydalis ethanol extraction (061129 group), Rhizoma Corydalis total alkaloids (061130), respectively to design 1 dosage group be 3g/kg, every group each 4, male and female hold concurrently half.Mice was prohibited the water non-fasting after 6-12 hour, weigh, irritate stomach by set dosage respectively and tried thing corydalis tuber water soluble part medicament (051901 group), Rhizoma Corydalis ethanol extraction (061129 group), Rhizoma Corydalis total alkaloids (061130), the administration volume is respectively 0.2ml/10g, to the response situation that is subjected to observe animal immediately behind the reagent thing, continue to observe 30 minutes, each was observed once in 1-4 hour, to note animal poisoning symptom and the cause of death and itemized record in 6 hours after the administration especially, generally to observe animal dead number and toxic reaction in 7-14 days after the administration, by day observation and itemized record animal toxicity reaction performance and characteristics, the time of toxic reaction appearing and subsiding, the distribution of dead animal in death time and each the dosage group is weighed and observe twice every day.Observe the symptoms and comprise: action, nervous system reaction, autonomic nervous system reaction and dead.
4. experimental result:
Rhizoma Corydalis ethanol extraction (061129 group), Rhizoma Corydalis total alkaloids (061130 group) are respectively organized the mice administration and are all occurred in various degree symptom after 45 minutes, and symptom shows as restlessness at first, occur after 2 hours lazy moving, lethargy.Corydalis tuber water soluble part medicament (051901 group) mice administration symptom do not occur in 2 hours.Behind the medicine in 8 hours 061129 group dead 2,061130 group dead 4,051901 group does not have death, all does the dissection no abnormality seen.Respectively organize survival mice behind the medicine after 48 hours, recover normal gradually.
Death condition sees following table for details behind the mice medicine:
Toxicity test shows as a result, and the prepared corydalis tuber water soluble part medicament toxicity of the present invention is low, safe, and good application prospects is arranged.
Claims (6)
1. the preparation method of a corydalis tuber water soluble part medicament is characterized in that, described method comprises the steps:
(1) corydalis tuber medicinal material is ground into coarse powder, extracts three times with 80% alcohol heating reflux of 6 times of amounts, each 4 hours, merges three times extracting solution, reclaim, concentrated, obtain relative density and be the Rhizoma Corydalis extracting solution of 1.02-1.06 at 50 ℃;
(2) with the extracting solution of step (1) through the macroporous resin column purifies and separates, macroporous resin is selected among D201, D101, AB-8, the X-5 any, the weight ratio of the consumption of macroporous resin and Rhizoma Corydalis extracting solution is 3-6: 1;
(3) macroporous resin column of step (2) having been adsorbed the Rhizoma Corydalis active site is carried out eluting with the water of 6-8 times of column volume, collects water elution liquid, reclaims moisture content, drying, promptly gets corydalis tuber water soluble part medicament.
2. preparation method according to claim 1 is characterized in that, the described resin column bed of step (2) blade diameter length ratio is 1: 4, and the Rhizoma Corydalis extracting solution is 1BV/h through the speed of macroporous resin column.
3. preparation method according to claim 1 is characterized in that, the flow velocity degree of the described eluting water of step (3) is 1BV/h.
4. preparation method according to claim 1 is characterized in that: the corydalis tuber water soluble part medicament of this method preparation, and yield is 6%～8%, wherein the Main Ingredients and Appearance general flavone content is greater than 15%.
5. the corydalis tuber water soluble part medicament of preparation method according to claim 1 preparation is used for the treatment of purposes in the medicine of coronary heart disease, angina pectoris, acute myocardial infarction in preparation.
6. according to the corydalis tuber water soluble part medicament of claim 1 or the preparation of 4 or 5 described preparation methoies, add conventional pharmaceutic adjuvant useful in preparing drug formulations, this pharmaceutical preparation is selected from any in capsule, tablet, drop pill, the oral liquid, and the dosage that contains corydalis tuber water soluble part medicament in the preparation is 200-300mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810061904XA CN101284050B (en) | 2008-05-09 | 2008-05-09 | Corydalis tuber water soluble part medicament and its preparation method and application |
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| CN102706999B (en) * | 2012-02-20 | 2016-03-30 | 浙江康恩贝制药股份有限公司 | The analyzing detecting method of corydalis tuber water soluble non-alkaloid compounds |
| CN102786433B (en) * | 2012-03-15 | 2016-09-21 | 浙江康恩贝制药股份有限公司 | A kind of fumaryl aminated compounds extract and its preparation method and application |
| WO2014000119A1 (en) * | 2012-06-25 | 2014-01-03 | 佛山市顺德区合生源医药研发有限公司 | Anti-tachyarrhythmia formulation and preparation method thereof |
| CN103417644B (en) * | 2013-08-08 | 2016-03-09 | 四川师范大学 | A kind of Heiguteng exract compound extract and its production and use |
| CN103623064B (en) * | 2013-11-15 | 2015-12-30 | 辽宁中医药大学 | A kind of isolation and purification method of Rhizoma Corydalis total alkaloids |
| CN109503571A (en) * | 2018-12-06 | 2019-03-22 | 金华职业技术学院 | A kind of method of dehydrocorydaline in D101 macroporous resin purification rhizoma corydalis |
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| CN1413655A (en) * | 2002-10-14 | 2003-04-30 | 刘建勋 | Medicine for treating ischemic angiocardiopathy and cerebrovascular disease and its preparation method |
| CN1650899A (en) * | 2004-02-02 | 2005-08-10 | 姜伟 | Method of extracting compound pain relieving medicament from natural plant effective component |
| CN1660914A (en) * | 2004-12-03 | 2005-08-31 | 中国科学院上海有机化学研究所 | Polysaccharide of rhizoma corydalis, preparation method and application |
| CN101057890A (en) * | 2006-04-20 | 2007-10-24 | 周亚伟 | Traditional Chinese medicinal composition for treating coronary heart disease and its preparation method, preparations and its application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1413655A (en) * | 2002-10-14 | 2003-04-30 | 刘建勋 | Medicine for treating ischemic angiocardiopathy and cerebrovascular disease and its preparation method |
| CN1650899A (en) * | 2004-02-02 | 2005-08-10 | 姜伟 | Method of extracting compound pain relieving medicament from natural plant effective component |
| CN1660914A (en) * | 2004-12-03 | 2005-08-31 | 中国科学院上海有机化学研究所 | Polysaccharide of rhizoma corydalis, preparation method and application |
| CN101057890A (en) * | 2006-04-20 | 2007-10-24 | 周亚伟 | Traditional Chinese medicinal composition for treating coronary heart disease and its preparation method, preparations and its application |
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