CN1526401A - Medicine composition for treating coronary heart disease and its prepn process, use and guality control method - Google Patents
Medicine composition for treating coronary heart disease and its prepn process, use and guality control method Download PDFInfo
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Abstract
The present invention is medicine composition for treating coronary heart disease and its preparation process, use and quality control method. The active component of the medicine is rhodiola glycoside prepared with rhodiola root. Rhodiola glycoside identifying thin-layer chromatography adopts developing agent comprising ethyl acetate, methanol and formic acid and developer comprising 1 % concentration FeCl3 and 1 % concentration potassium ferricyanide. The efficient liquid phase chromatography for determining rhodiola glycoside content has the conditions of: octadecyl silane linked silicone gel as stuffing, methanol-water-glacial acetic acid flowing phase, flow rate 0.9 ml/min, detection wavelength 276 nm, column temperature 40 deg.c and theoretic column plate not less than 7000.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for the treatment of coronary heart disease and preparation method thereof, purposes and method of quality control.
Background technology
Coronary heart disease is a kind of common cardiovascular disease.As far back as the sixties, its sickness rate is the just constantly rising of some countries in the west, and becomes first of the human death.For example, have only the U.S. of 200,000,000 populations, that dies from coronary heart disease every year has 700,000 people approximately, accounts for 1/3 of death toll, is called as " first killer ".In China, along with improving constantly of living standards of the people, population is relatively lagging behind of aging and prevention and health care work day by day, and the persistence rising has all appearred in prevalence of coronary heart disease, M ﹠ M.National reconnaissance information according to 1973 shows, coronary heart disease average attack rate only 6.46%, by 1975 seven geographic mass survey such as Beijing, Shanghai, Guangzhou, Sichuan are shown, the Incidence of CHD of 30-69 year age group is 1.65-6.11%, and crowd's sickness rate rises to 8.65-24.3% more than 60 years old.In recent years, sickness rate obviously rises, and illustrates that the task of control is very heavy, should cause people's attention.
Develop rapidly along with the modern science technology, people have also obtained some progress to coronary heart disease diagnosis and control, as aspect the inspection, by original routine electrocardiogram, load ECG inspection, be updated to dynamic ecg recordings examination, ultrasonic cardiography inspection art, Electrocardiographic computerization, nuclear myocardial perfusion imaging scanning, coronary angiography, the application of electron beam ct machine.Biochemical analysis and cardiac determination method are being updated, for early diagnosis provides excellent means.Aspect preventing and treating, comprise the foundation, coronary artery bypass grafting of CCV, the foundation etc. of logical art again; Drug treatment on the basis of coronary artery dilating, the application of calcium ion antagonist, a receptor blocking agent, thrombolytic drug occurred, for treatment coronary heart disease provides multiple means.Yet clinical practice confirms that simple western medicine is unsatisfactory toward contact, and the especially side reaction of medicine makes the patient be difficult to accept and take for a long time.Contemporary mankind's's " back to nature " hope and cry are strong day by day, the general flat natural nuisance-free plant amedica treatment wished, thus the opportunity of knowing clearly is provided for Chinese medicine prevention coronary heart disease.The pure tcm product of developing a kind of efficient, low toxicity, stay-in-grade treatment coronary heart disease is the place of our purpose.
Summary of the invention
The active component of the application's medicine is rhodioloside (C
14H
20O
7), the content in the medicine of unit dose must not be less than the 0.8mg/ unit dose.Usually make by the water or the alcohol extract of Radix Rhodiolae or Radix Rhodiolae.This product has blood circulation promoting and blood stasis dispelling, the effect of coronary circulation-promoting pain-relieving.Cure mainly the obstruction of qi in the chest and cardialgia (angina pectoris) that stagnation of heart-blood causes, disease such as chest distress, shortness of breath and palpitation, shortness of breath and palpitation, sleepy weak, thready and hesitant pulse.
The application's medicine can adopt the conventional method of galenic pharmacy to make regular dosage form, and as powder, tablet, electuary, oral liquid, injection etc., preferred dosage form is a capsule.Below be the preparation method of 3 kinds of indefinitenesses of product of the present invention, method in addition is also in the application's protection domain.
Method for making 1. is got 1100 parts of Radix Rhodiolae medical materials (the dry root and rhizome of Crassulaceae plant rhodiola kirilowii Regel RhodiolaKirilowii (Regel) Maxim.), adding 8 times of water gagings boiled 1.5 hours, filter, medicinal residues add 6 times of water gagings again and boiled 1.5 hours, filter, merge medicinal liquid twice, be condensed into extractum, get the about 190～200g of cream amount, relative density 1.2～1.25 (60 ℃ of mensuration), get 1 part of extractum and add 1.25～1.35 parts of mixings of starch, dry below 80 ℃, pulverize, with debita spissitudo ethanol system granule, oven dry, granulate, encapsulated, get 1000 of capsules, every heavy 0.38g is equivalent to crude drug 1.1g.Or make tablet, granule; Or the food plant wet goods suspensoid that adds 1～3 part behind the above-mentioned extract dry made soft capsule.Salidroside content in this unit dose is no less than 0.8mg.
Method for making 2. is got the Radix Rhodiolae medical material, add 8 times of water gagings and boiled 1.5 hours, filter, medicinal residues add 6 times of water gagings again and boiled 1.5 hours, filter, merge medicinal liquid twice, concentrating under reduced pressure becomes 50 ℃ of relative density 1.05-1.07, adds 95% alcoholic solution and makes the alcohol amount of containing reach 50-70%, cold preservation was placed 20-26 hour, filter, reclaim ethanol to there not being the alcohol flavor, and to be concentrated into 50 ℃ of following relative densities be 1.05-1.06, cooling, thin up to each parts by volume medicinal liquid is equivalent to crude drug 0.44 weight portion, filters, and adds 0.1～0.15% tween 80, mixing, make oral liquid, be sub-packed in the 10ml oral liquid bottle, every bottle of salidroside content is no less than 1.5mg.
Method for making 3. is got Radix Rhodiolae medical material 40-60 weight portion, adding 8 times of water gagings boiled 1.5 hours, filter, medicinal residues add 6 times of water gagings again and boiled 1.5 hours, filter, and merge medicinal liquid twice, concentrating under reduced pressure becomes 50 ℃ of relative density 1.05-1.07, add 95% alcoholic solution and make the alcohol amount of containing reach 50-70%, cold preservation was placed 20-26 hour, filtered, reclaim ethanol to there not being the alcohol flavor, and to be concentrated into 50 ℃ of following relative densities be 1.05-1.06, adds 60～80 ℃ of water for injection 1000 parts by volume and stir, and makes dissolving, add sodium chloride 3～8 weight portions, transfer pH value to 6.0～6.5 with 40% sodium hydroxide solution, cooling is filtered, reuse 10000D molecular weight ultrafilter membrane, the following molecular weight ultrafilter membrane of 5000D classification ultrafiltration, added needle-use activated carbon 2～4 weight portion stirring and adsorbing 10～30 minutes, and filtered carbon removal, filtrate adds injection water to 1000 parts by volume, serve as a contrast the 0.22m filtering with microporous membrane down with aseptic filter plate, the medicinal liquid packing, sterilization, promptly.
This product also can be made by the ethanol extraction of Radix Rhodiolae with 30-70%.
Character this product is a capsule, the conspicuous red powder of content, bitter in the mouth.
The discriminating thing of getting it filled is an amount of, extract with the ethanol heat of 70-100% concentration, or it is an amount of to get the medicine of liquid dosage form, ethanol heat with 70-100% concentration behind the evaporate to dryness is extracted surplus residue, filters, and filtrate is concentrated into dried, residue adds ethanol makes dissolving in right amount, as need testing solution; Other gets the rhodioloside reference substance and adds ethanol and make solution, product solution in contrast, each is an amount of to draw above-mentioned two kinds of solution, put respectively in same and contain on the silica gel G thin layer that sodium carboxymethyl cellulose is a binding agent, with ethyl acetate-methanol-formic acid (9: 1: 0.8) is developing solvent, launch, taking-up is dried, and spray is with 1%FeCl
3-1% potassium ferricyanide (1: 1) solution is put under the daylight and is inspected, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical blue mottle point.
Assay is measured (two points external standard method) according to high performance liquid chromatography (39 pages of " Pharmacopoeia of People's Republic of China 2000 version one one " appendix).
System suitability test: with octadecylsilane chemically bonded silica is filler, and methanol-water-glacial acetic acid (7: 93: 1) is a mobile phase, and flow velocity 0.9ml/min detects wavelength 276nm, 40 ℃ of column temperatures, and theoretical cam curve is calculated by the rhodioloside peak should be not less than 7000.
The preparation of reference substance solution: precision takes by weighing the about 10mg of rhodioloside reference substance, puts in the 25ml dissolve measuring bottle.Be dissolved in water, and be diluted to scale, in contrast product solution.
The preparation of need testing solution and mensuration: it is an amount of that precision takes by weighing medicine, or get the medicinal liquid evaporate to dryness of respective amount, put in the flask, the ethanol that adds 90-100% concentration is an amount of, and heat is extracted, and filters, filtering residue is with washing with alcohol three times, merging filtrate also is concentrated into driedly to the greatest extent, and residue adds water makes dissolving, is added on polyamide column, water carries out eluting, accurately collect the eluent certain volume, as need testing solution, each is an amount of to draw reference substance solution and need testing solution, inject chromatograph of liquid, measure peak area, external standard method is calculated, promptly.
This product content contains rhodioloside (C
14H
20O
7), must not be less than the 0.8mg/ grain.
Usage and dosage is oral.One time 4,3 times on the one.
Drug efficacy study shows: by the capsule that Radix Rhodiolae is made, heavy dose of group then makes myocardial contractility enhancing in the myocardial ischemia process after giving the dog gastric infusion, and can improve the hemodynamic situation of heart; With visceral pericardium electrocardiogram (positive ST and NST) is that the observation of index shows that the large and small dosage group of capsule all can alleviate the treating myocardial ischemia damage degree after administration, dwindle damage range; With heart vim and vigour and oxygen metabolism and arteria coronaria flow is that index observing arrives, myocardium oxygen extraction ratio increases to some extent in the myocardial ischemia process, arteria coronaria hole blood PH value and arteria coronaria flow obviously descend, the heavy dose of group of capsule then can suppress the decline of coronary flow, heart oxygen extraction ratio when reducing myocardial ischemia, and heart coronaries venous sinus blood PH value is raise, thereby alleviate the acidosis of myocardial cell.We have carried out the second stage of clinical research year June in July, 1996 to 1997 to the clinical effectiveness that Rhodiola rosea capsules is treated obstruction of qi in the chest and cardialgia (angina pectoris), clinical test results is: the obstruction of qi in the chest and cardialgia of treatment group at random obvious effective rate is 46.00%, total effective rate 90.00%; Open treatment group obstruction of qi in the chest and cardialgia obvious effective rate is 44.78%, and total effective rate is 86.07%; Total treatment group (treatment group 1+ treatment group 2) obstruction of qi in the chest and cardialgia obvious effective rate is 45.18%, and total effective rate is 87.37%; The electrocardiogram obvious effective rate is 26.25%, and total effective rate is 60.13%.Matched group obstruction of qi in the chest and cardialgia obvious effective rate is 27.00%, and total effective rate is 72.00%, and the electrocardiogram obvious effective rate is 11.00%, always effectively is 40.00%.Learn processing by statistics for two groups, p＜0.05, treatment group curative effect is better than matched group.
The drug efficacy study data of Rhodiola rosea capsules
This research is divided into the heavy dose of group of normal group, model group, FUFANG DANSHEN PIAN matched group, capsule small dose group and capsule, 5 every group at random with 25 of healthy hybrid dogs.The ligation arteria coronaria causes the acute myocardial ischemia model between the 2nd, 3 branches of the ramus descendens anterior arteriae coronariae sinistrae of dog, having observed medicine irritates after stomach gives dog, the influence of indexs such as myocardial contractility, cardiac hemodynamic, visceral pericardium electrocardiogram, LC coronary flow, heart vim and vigour and oxygen metabolism during to expeirmental myocardial ischemia is estimated Rhodiola rosea capsules and is had or not the effect and the dose-effect relationship thereof for the treatment of coronary heart disease.
Materials and methods
One, laboratory animal and grouping
Select 25 of the healthy hybrid dogs that the PLA General Hospital Animal House provides for use, be divided into five groups at random, normal group, model control group (abbreviation model group), FUFANG DANSHEN PIAN matched group (being called for short the Radix Salviae Miltiorrhizae group), capsule small dose group (abbreviation small dose group) and the heavy dose of group of capsule (being called for short heavy dose of group), every group each 5, each treated animal female-male proportion is basic identical.
Two, be subjected to the reagent thing
Rhodiola rosea capsules (hereinafter to be referred as capsule), every heavy 0.38g is equivalent to crude drug 1.1g.The reference substance FUFANG DANSHEN PIAN, Liaoning Huanren Chinese Pharmaceutical Factory produces, every heavy 0.25g.
Three, be subjected to the preparation of reagent thing
Get Rhodiola rosea capsules, remove capsule shells, it is an amount of to take by weighing medicated powder, and the limit adds the normal saline limit and grinds in mortar, makes to contain among the 1ml to contain two kinds of suspensions of 0.5g crude drug (being called for short A liquid, B liquid successively) among 1g crude drug and the 1ml.FUFANG DANSHEN PIAN is also dissolved with normal saline and is made the solution (being called for short C liquid) that contains tablet 0.33g among the 1ml.
Four, dosage and method
Capsule heavy dose of 1.5ml/kg that presses give A liquid, promptly presses 1.5g crude drug/kg administration, quite 11 times of people's consumption; The capsule small dose group is pressed 1.5ml/kg and is given B liquid, promptly presses 0.75g crude drug/kg administration, is equivalent to 5.5 times of people's consumption, and the Radix Salviae Miltiorrhizae group is pressed 1.5ml/kg and given C liquid, promptly presses 0.5g/kg and gives FUFANG DANSHEN PIAN, is equivalent to 11 times of people's consumption; Model group is pressed 1.5ml/kg and is given 1.5% carboxymethyl cellulose.Except that not administration of normal group, all the other each groups are all through the stomach tube administration.
Five, experimental procedure
All animals are adopted pentobarbital sodium intraperitoneal injection of anesthesia (30mg/kg), and intubate after the tracheotomy is kept the artificial respiration with the electronic breath device of SC-2 type.Separate left carotid and right side external jugular vein in order to intubate, transfemoral catheterization of femoral vein constant speed input normal saline (about 20 droplets/minute) is with replenishment of blood content.The 4th intercostal is opened breast along the left side, the about 1.5cm of example cuts off pericardium and makes the pericardium bed in the place in phrenic nerves, free aortic root also settles ME-27 type electromagnetic flowmeter probe (selecting the probe of different model size according to aorta external diameter thickness) in order to measuring cardiac output (CO), routine common carotid artery entad is inserted into aortic root through a left side with a 6#F cardiac catheter, in order to measuring the tremulous pulse blood sample and measuring arteriotony, with another root 6#F cardiac catheter in right side neck outer tube arteries and veins centripetal direction inserts coronary sinus vein, in order to extracting the venous samples can of heart, (apart from LAD initial part 1.5～2cm place) separation coronary artery causes myocardial ischemia in order to ligation between ramus descendens anterior arteriae coronariae sinistrae (LAD) 2-3 branch then, sub-LCA start-up portion measures coronary flow from one section tremulous pulse of about 1.5～2cm in order to settling electromagnet flow meter sensor; Directly insert left ventricle to measure left ventricular pressure power indexs such as (LVP) with a 7#F cardiac catheter in apex, fill in each cardiac catheter with heparin solution (0.2%); TH602T type tension force after improvement bow is directly inserted the predetermined ischemic region of left chamber antetheca, and the major axis of tension force bow is consistent with left chamber surface cardiac muscle fiber traveling, and makes the cardiac muscle fiber drafted about about 30% between two bows.One stomach tube intubate is directly inserted through the oral cavity in the stomach, prepared against various experiments of perfusion and contrast medicine, all animals all extracted heart arter and venous samples can in 30 minutes in postoperative, and control value before the normal ischemia of record physical signs conduct; Except that normal group, all the other are respectively organized equal ligation ramus descendens anterior arteriae coronariae sinistrae and cause myocardial ischemia, behind ischemia, write down every index again in 30 minutes and take a blood sample, test medicine group and control drug group then all through the stomach tube administration, neither also not administration of ischemia of normal group, all the other steps are all with above-mentioned each group, and each organizes after administration 30 minutes, 60 minutes and 90 minutes each once every indexs of record and taking a blood sample, and write down five times altogether front and back.
Six, observation index and instrument
1. visceral pericardium ECG ST section, connect RD-5 biophysics amplifier mapping visceral pericardium electrocardiogram by filamentary silver one cotton core electrode, electrode place ischemia center and marginal zone totally 12 raise scope above number (NST) the expression myocardial ischemia that leads of 2mv, the degree of the magnitude of voltage summation of raising with the ST section (∑ ST) expression myocardial ischemic injury with the visceral pericardium ECG ST section.
2. heart rate (HP), by calculate during the R-R of 60/FCG (inferior/min).
3. left ventricular pressure power peak value (LVSP) is connected to the apex ventricular catheter and connects the RP-6 carrier amplifier behind the MPU-0.5A type pressure transducer and measure.
4. left ventricular pressure rate of change (dp/dt) obtains left ventricular pressure signal input RPD-5 differential amplifier, is the maximum climbing speed (dp/dtmax) of left ventricular pressure by baseline to dp/dt forward highest point; By baseline to the reverse lowest part of dp/dt be the maximum fall off rate of left indoor pressure (_ dp/dtmax).
5. mean arterial pressure (MAP) is connected to MPU-0.5A type pressure transducer with the common carotid artery intubate and connects the acquisition of RP-5 carrier amplifier.
6. cardiac muscle development tension force (DT) is connected to the RP-5 carrier amplifier with the TH-602T type tension force bow of stator ischemic region and records.
1～6 index adopts Japanese photoelectricity company to produce RM86 type polygraph and records.
7. cardiac output (CO) is connected to the product MF-27 of Japanese photoelectricity company type electromagnetic flowmeter with the electromagnetic flowmeter probe that is installed in aortic root and directly reads CO value (L/min).
8. coronary flow (CBF) is connected to the product MF-120 of Japanese photoelectricity company type electromagnetic flowmeter with the electromagnetic flowmeter probe that hands LC arteria coronaria is installed and directly measures.
9. the heart blood gas analysis injects Denmark product ABL-2 type vim and vigour automatic analyzer immediately with arterial blood and each the about 0.5ml of crown venous sinus blood sample that extracts, and directly measures the partial pressure of carbon dioxide (PaCO of artery and vein blood
2, PvCO
2), oxygen saturation (SaO
2, SvO
2), hemoglobin concentration (Hba, HBv) and PHv value etc. calculate quiet, the poor (Pv-aCO of tremulous pulse of partial pressure of carbon dioxide then
2), the poor (Sa-vO of the arteriovenous of blood oxygen saturation
2).
10. heart oxygen extraction ratio (O
2E): calculate by following formula:
Wherein: Cz-vO
2=(SaO
2* Hba * 1.39)-(SvO
2* HBv * 1.39)
CaO
2＝SaO
2×Hba×1.39
Seven, statistical procedures
This is tested used data and is measurement data, all adopts the T check when carrying out significance test.
Interior P＜0.05, P＜0.001 of comparing of group of detected value mutually when all represent in each group behind the ischemia 30 ' time detected value and preceding respective value of ischemia and administration each respectively in each table of this paper with " * ", " * * " and " * * * ", with " Δ " " Δ Δ " " Δ Δ Δ " respectively the representation model group each the time phase detected value corresponding value P＜0.05 relatively when respectively organizing each with other, P＜0.01 and P＜0.001.
Result and analysis
The influence of heart hydromechanics (seeing attached list 1) when 1, Rhodiola rosea capsules is to the dog expeirmental myocardial ischemia
From table 1, as seen, respectively organize relatively all no significant differences (P all＜0.05) of every index before the ischemia, show that the preceding foundation level of each treated animal ischemia is identical substantially.30 ' time of ischemia, the big small dose group of capsule, Radix Salviae Miltiorrhizae group and model group MAP, CO reduce, LWEDP raises, with value before the ischemia and normal group analog value significant difference (P＜0.005 or P＜0.01) is arranged more all, HR then changes not quite, The above results shows that myocardial ischemia suffers damage cardiac hemodynamic; And the large and small dosage group of capsule is compared with ischemia group with the Radix Salviae Miltiorrhizae group, and the equal no significant difference of every index (P＞0.05) shows the disorderly degree basically identical of above-mentioned three groups of hemodynamics that cause because of myocardial ischemia.Model group MAP, CO further reduce behind the medicine, LVEDP continues to raise, though the change of same direction appears in each Radix Salviae Miltiorrhizae group of testing medicine group and contrast, but degree is lighter, and especially the heavy dose of group of capsule is compared with model group, and all there is significant difference (P＜0.05) in 90 ' time after administration such as MAP and CO, show that the heavy dose of group of capsule can improve the hemodynamics of heart, on effect, the heavy dose of group of capsule is better than the Radix Salviae Miltiorrhizae group, and the Radix Salviae Miltiorrhizae group is better than the capsule small dose group.
2. the influence of myocardial contractility (seeing attached list 2) when Rhodiola rosea capsules is to the dog expeirmental myocardial ischemia
From subordinate list 2 as seen, parameters relatively before the ischemia, no significant difference (P＞0.05) between each group, foundation level is identical substantially before showing each treated animal ischemia, ischemia is in the time of 30 minutes, the big small dose group of capsule, Radix Salviae Miltiorrhizae group and model group DT, LVSP, dp/dtmax ,-dp/dtmax reduces, show that myocardial ischemia makes left chamber myocardial contraction mechanics performance be subjected to comparison between infringement and above-mentioned each group, the equal difference of every index little (P＞0.05) illustrates the above-mentioned undermined degree basically identical of myocardial contractility of respectively organizing after the intubate.Model group prolongs with Ischemia Time, and above-mentioned every index continues to descend.Though 90 ' each medicine also has decline to the medicine, degree is lighter, compare with model group, except that LVSP all the other every indexs behind medicine 60 ' or 90 ' time significant difference (P＜0.05) is all arranged.Show that large and small dosage group of capsule and Radix Salviae Miltiorrhizae group all can protect the function of Ischemic Heart; the further infringement of the myocardial contractility that inhibition causes because of ischemia; on effect, capsule small dose group and Radix Salviae Miltiorrhizae category seemingly, the heavy dose of group of capsule then slightly is better than capsule small dose group and Radix Salviae Miltiorrhizae group.
The Electrocardiographic influence of visceral pericardium when 3, Rhodiola rosea capsules is to the dog expeirmental myocardial ischemia (seeing Table attached 3)
Result's demonstration of subordinate list 3, the relatively more equal no significant difference (P＞0.05) of ∑ ST of each group and NST before the ischemia shows that the preceding foundation level of each treated animal ischemia is identical substantially.Ischemia in the time of 30 minutes each medicine group (comprising large and small dosage of capsule and Radix Salviae Miltiorrhizae group) and model group ∑ ST, NST all increase, with before the ischemia and the corresponding duration of normal group significant difference (P＜0.01) is more all arranged, show that the ligation arteria coronaria is accused to have caused myocardial ischemic injury; And each medicine group and model group ratio, two equal no significant differences of index (P＞0.05) illustrate and respectively organize degree of myocardial ischemia and scope basically identical.Behind the medicine, model group ∑ ST and NST further increase; Though each medicine group NST also increases, but degree is lighter, ∑ ST and each medicine stretch tight and then decrease, compare with model group, two indexs behind medicine 60 ' or 90 ' time notable difference (P＜0.05 or P＜0.01) is arranged, show that large and small dosage of capsule and Radix Salviae Miltiorrhizae group effect are similar, the effect of capsule small dose group then is slightly poorer than preceding two groups.
The influence (seeing attached list 4) of coronary flow and myocardium oxygen extraction ratio when 4, Rhodiola rosea capsules is to the experimental myocardium blood of dog
Subordinate list 4 shows, respectively organizes coronary flow (CBF) and heart oxygen extraction ratio (O before the ischemia
2E) equal no significant difference (P all＞0.05) shows that the preceding foundation level of each treated animal ischemia is identical substantially.Ischemia in the time of 30 minutes each medicine group coronary flow reduce and O
2E then raises, and each medicine group is compared with model group, and the equal no significant difference of each index (P＞0.05) points out each treated animal because of myocardial blood flow supply and the unusual degree basically identical of oxygen metabolism due to the ischemia.Behind the medicine 30 ' to the medicine 90 ', the reduction of model group coronary flow does not then have model group obvious, to medicine 60 ' or 90 ' time, the Radix Salviae Miltiorrhizae group obviously raises (P＜0.05) decline of coronary flow when pointing out these two groups of medicines to prevent myocardial ischemia with the heavy dose of group of capsule than model group is relative; And O
2E is in 30 ' 90 ' time to medicine behind the medicine, model group is high basically, each medicine thing group (comprising large and small dosage group of capsule and Radix Salviae Miltiorrhizae group) then all has decline in various degree, to medicine 60 ' and 90 ' time, mass dosage capsule group and Radix Salviae Miltiorrhizae group are starkly lower than ischemia group (P＜0.05), show the raising of cardiac muscle oxygen extraction ratio when these two groups of medicines have suppressed myocardial ischemia, on effect, the effect of capsule small dose group is obvious not as the heavy dose of group of capsule and Radix Salviae Miltiorrhizae group, and then both effects are close.
The influence of heart vim and vigour (seeing attached list 5) when 5, Rhodiola rosea capsules is to the dog expeirmental myocardial ischemia
As seen from the table, respectively organize the poor (Pv-aCO of the quiet tremulous pulse of partial pressure of carbon dioxide before the ischemia
2) and the more equal no significant difference of vein pH value (PHv) (P＞0.05), ischemia is in the time of 30 minutes, each medicine group (large and small dosage group of capsule and Radix Salviae Miltiorrhizae group) and model group Pv-aCO
2Increase PHv and reduce, show that ischemia has caused the myocardial metabolism product to pile up the blood souring; Each medicine group is compared with model group, and the equal no significant difference of every index (P＞0.05) is pointed out each treated animal degree of ischemia basically identical.Behind the medicine 30 ' to 90 ', model group Pv-aCO
2Further increase, PHv further reduces, though each medicine group is similar variation, but degree is lighter, compare with model group, heavy dose of level of capsule and Radix Salviae Miltiorrhizae group PHv behind medicine 60 ' or 90 ', the time explicitly difference (P＜0.05) arranged, point out above-mentioned two medicines to be in prison and make the carbon dioxide accumulation that ischemia causes, prevent that the acidification of blood aspect from having certain effect.And the relative effect of capsule small dose group is slightly poor, with behind the model group comparison medicine 30 ' there is no significant difference to 90 ' time.
Conclusion: 1, heavy dose of group of capsule and Radix Salviae Miltiorrhizae group all can be improved the cardiac hemodynamic disorder that causes because of ischemia to some extent, and the former effect slightly is better than the latter, and the effect of capsule small dose group is then very unobvious.
2, large and small dosage group of capsule and Radix Salviae Miltiorrhizae group all can prevent the abnormal change of myocardial contraction performance in the expeirmental myocardial ischemia process to a certain extent, and wherein capsule small dose group and Radix Salviae Miltiorrhizae group effect are similar, and the heavy dose of group of capsule is better than the first two group.
3, large and small dosage group of capsule and Radix Salviae Miltiorrhizae group all can alleviate the degree and the damage range of myocardial ischemic injury, and on effect, the heavy dose of group of capsule is similar to the effect of Radix Salviae Miltiorrhizae group, and the effect of capsule small dose group is inferior slightly than the first two group.
The rising of cardiac muscle oxygen extraction ratio and the reduction of coronary flow when 4, heavy dose of group of capsule and Radix Salviae Miltiorrhizae group can suppress myocardial ischemia, point out these two groups of medicines can improve the blood supply state of ischemic myocardium, the coefficient of oxygen utilization of cardiac muscle when improving ischemia, the capsule small dose group does not then have positive effect.
5, capsule is big, the increase of the quiet tremulous pulse difference of arteria coronaria hole blood partial pressure of carbon dioxide when small dose group and Radix Salviae Miltiorrhizae group can prevent myocardial ischemia to some extent, but there is no tangible statistical significance; Heavy dose of group of capsule and Radix Salviae Miltiorrhizae group can obviously suppress the decline of arteria coronaria hole blood PH value behind the myocardial ischemia, alleviate the acidosis of ischemic myocardial cell, and the capsule small dose group do not have positive effect to this.
Take a broad view of above-mentioned, Rhodiola rosea capsules can suppress the ischemic lesions of cardiac muscle, alleviate the extent of damage, dwindle damage range, alleviate the acidosis of ischemic myocardial cells, and can correct the cardiac hemodynamic disorder in the expeirmental myocardial ischemia process, improve ischemic myocardium blood supply situation, improve its coefficient of oxygen utilization, thus the cardiac function when improving idle property myocardial ischemia; What can not be ignored is that the above-mentioned action intensity of Rhodiola rosea capsules is relevant with its dosage.
Table 1 Rhodiola rosea capsules is to the influence of acute myocardial ischemia dog cardiac hemodynamics (M ± SD)
Before the group ischemia behind ischemia 30 ' medicine behind 30 ' medicine behind 60 ' medicine 90 '
Normal group 70.8 ± 8.74 69.3 ± 8.01 68.7 ± 7.61 68.5 ± 6.91 Δ 68.6 ± 7.20 Δs
MAP model group 73.69.70 59.5 ± 8.16* 57.3 ± 8.32 55.7 ± 7.23 54.3 ± 7.03
(average small dose group 76.1 ± 7.97 62.7 ± 8.07* 66.4 ± 8.21 65.7 ± 7.93 64.9 ± 7.87
Arterial pressure) heavy dose group 73.2 ± 8.72 64.1 ± 7.98 65.2 ± 8.13 65.0 ± 8.24 66.6 ± 8.18 Δs
(mmHg) Radix Salviae Miltiorrhizae group 75.4 ± 9.12 61.9 ± 8.28* 65.1 ± 8.21 63.9 ± 8.49 64.1 ± 8.74
Normal group 134.0 ± 13.14 132.4 ± 11.50 128.8 ± 12.10 127.0 ± 15.38 127.8 ± 15.70
HR model group 136.0 ± 12.88 121.6 ± 11.42* 116.6 ± 10.24 112.4 ± 10.19 110.2 ± 9.63
(heart rate) small dose group 133.6 ± 12.14 117.0 ± 10.44* 112.6 ± 14.75 122.0 ± 13.25 121.0 ± 10.84
(inferior/minute) heavy dose of group 133.6 ± 12.29 116.4 ± 10.24* 124.4 ± 11.51 129.0 ± 12.10 123.0 ± 10.05
Radix Salviae Miltiorrhizae group 130.6 ± 12.26 119.8 ± 10.% 113.6 ± 11.72 115.8 ± 14.03 111.0 ± 14.35
Normal group 1.48 ± 0.27 1.45 ± 0.25 1.44 ± 0.36 Δ, 1.44 ± 0.28 Δ Δs, 1.37 ± 0.24 Δ Δs
CO model group 1.60 ± 0.24 1.12 ± 0.22* 0.99 ± 0.24 0.90 ± 0.20 0.87 ± 0.18
(heart is failed small dose group 1.56 ± 0.23 1.18 ± 0.21* 1.12 ± 0.24 1.09 ± 0.18 1.44 ± 0.22
Output) heavy dose group 1.51 ± 0.28 1.16 ± 0.33 1.14 ± 0.25 1.20 ± 0.21 Δ 1.16 ± 0.21 Δs
(L/ branch) Radix Salviae Miltiorrhizae group 1.54 ± 0.24 1.20 ± 0.22 1.19 ± 0.26 1.18 ± 0.23 1.18 ± 0.24 Δ
Normal group 2.60 ± 0.73 2.88 ± 0.71 Δ, 2.95 ± 0.65 Δs, 3.12 ± 0.67 Δs, 1.37 ± 0.24 Δ Δs
LVEDP model group 2.54 ± 0.61 4.20 ± 0.78** 4.42 ± 0.77 4.52 ± 0.70 4.68 ± 0.72
(defeated small dose group 2.75 ± 0.69 4.08 ± 0.67* 4.30 ± 0.65 4.51 ± 0.72 4.64 ± 0.68 of opening
Press at the end eventually) heavy dose of group 2.38 ± 0.64 4.32 ± 0.65** 4.37 ± 0.71 4.39 ± 0.79 4.44 ± 0.57
(mmHg) Radix Salviae Miltiorrhizae group 2.69 ± 0.76 4.51 ± 0.70** 4.50 ± 0.69 4.49 ± 0.68 4.52 ± 0.69
Table 2 Rhodiola rosea capsules is to the influence of acute myocardial ischemia dog myocardial contractility (M ± SD)
Before the index group ischemia behind ischemia 30 ' medicine behind 30 ' medicine behind 60 ' medicine 90 '
Normal group 107.6 ± 10.3 102.4 ± 9.3 Δs 98.5 ± 11.4 98.1 ± 10.3 Δs, 95.9 ± 11.1 Δ Δs
LVSP model group 104.3 ± 9.4 38.7 ± 9.2* 84.6 ± 9.7 80.8 ± 11.0 74.2 ± 9.2*
(mmHg) small dose group 103.7 ± 11.0 88.4 ± 8.8* 84.6 ± 9.8 81.2 ± 10.1 79.1 ± 10.7*
Heavy dose of group 104.8 ± 11.4 90.5 ± 11.4 85.7 ± 10.2 86.2 ± 10.9 87.7 ± 10.8
Radix Salviae Miltiorrhizae group 102.4 ± 10.8 91.4 ± 10.9 86.5 ± 11.3 83.6 ± 12.1 82.2 ± 11.3
Normal group 2095 ± 278.2 1965 ± 229.3 1975 ± 204.1 1946 ± 208.4 Δ 1939 ± 198.9 Δs
Dp/dt model group 2141 ± 246.7 1871 ± 229.5 1767 ± 221.7 1638 ± 197.9 1550 ± 190.4*
MmHg/S small dose group 2168 ± 252.3 1903 ± 230.8 1882 ± 196.8 1859 ± 204.1 1834 ± 188.2 Δs
Heavy dose of group 2208 ± 238.4 1978216.1 1942 ± 221.2 1935 ± 203.7 Δ 1892 ± 201.3 Δs
Radix Salviae Miltiorrhizae group 2183 ± 228.2 1924 ± 207.5 1897 ± 204.1 1869 ± 132.3 1846 ± 203.1 Δs
Normal group 1481 ± 179.3 1427 ± 153.6 1399 ± 149.3 1371 ± 147.5 1359 ± 143.1 Δs
Dp/dt model group 1506 ± 173.6 1364 ± 137.2 1241 ± 131.5 1180 ± 128.4 1158 ± 127.6*
MmHg/s small dose group 1547 ± 164.2 1294 ± 144.1 1281 ± 137.8 1264 ± 131.6 1243 ± 131.8
Heavy dose of group 1531 ± 158.2 1391 ± 142.3 1387 ± 128.4 1398 ± 132.4 Δ 1377 ± 138.5 Δs
Radix Salviae Miltiorrhizae group 1497 ± 182.7 1328 ± 148.1 1298 ± 139.5 1271 ± 132.3 1279 ± 140.3
Normal group 56.2 ± 11.06 55.8 ± 9.88 Δs, 53.4 ± 9.00 Δ Δs, 53.4 ± 8.97 Δ Δs, 51.6 ± 9.39 Δ Δ Δs
DT model group 58.0 ± 12.8 34.4 ± 9.72* 31.0 ± 9.10 27.6 ± 8.54*, 22.4 ± 7.11*
(g) small dose group 59.3 ± 11.73 36.9 ± 9.95* 35.8 ± 8.94 34.8 ± 9.44 34.6 ± 9.06
Heavy dose of group 59.0 ± 11.34 38.1 ± 9.07* 36.3 ± 9.30 39.0 ± 9.45 42.4 ± 8.76 Δ Δs
Radix Salviae Miltiorrhizae group 57.6 ± 9.61 39.8 ± 9.72* 39.4 ± 9.30 38.1 ± 9.54 34.9 ± 8.67 Δs
Table 3 Rhodiola rosea capsules is to the influence of acute myocardial ischemia degree and scope (M ± SD)
Before the index group ischemia behind ischemia 30 ' medicine behind 30 ' medicine behind 60 ' medicine 90 '
Normal group 8.50 ± 3.01 9.76 ± 2.93 Δ Δ Δs, 10.02 ± 3.27 Δ Δ Δs, 10.54 ± 3.03 Δ Δ Δs, 10.66 ± 3.44 Δ Δ Δs
HST model group 8.46 ± 2.92 60.68 ± 16.74*** 82.47 ± 16.34 80.71 ± 9.61 93.72 ± 21.20
Small dose group 8.28 ± 2.87 61.34 ± 15.74*** 70.73 ± 20.97 60.67 ± 21.87 64.24 ± 17.38 Δs
Heavy dose of group 8.36 ± 2.96 50.41 ± 12.23*** 60.58 ± 13.14 63.54 ± 14.20 Δs, 60.39 ± 13.23 Δs
Radix Salviae Miltiorrhizae group 7.98 ± 3.10 56.93 ± 11.20*** 59.16 ± 11.86 61.41 ± 11.29 Δs, 63.41 ± 14.01 Δs
Normal group 2.10 ± 0.74 2.51 ± 0.82 Δ Δ Δ, 2.64 ± 0.87 Δ Δ Δs, 2.75 ± 0.78 2.01 ± 0.82 Δ Δ Δs
∑ ST model group 1.96 ± 0.76 9.25 ± 1.25*** 10.11 ± 1.14 10.37 ± 1.13 10.56 ± 1.18
Small dose group 2.03 ± 0.79 9.31 ± 1.34*** 9.83 ± 1.31 8.89 ± 1.46 8.37 ± 1.14 Δs
Heavy dose of group 1.87 ± 0.71 8.96 ± 0.95*** 8.58 ± 0.98 8.21 ± 0.89 Δ, 6.45 ± 0.92 Δ Δs
Radix Salviae Miltiorrhizae group 1.94 ± 0.76 9.05 ± 1.07** 8.77 ± 0.91 8.42 ± 0.97 Δ, 6.78 ± 0.94 Δ Δs
Table 4 Rhodiola rosea capsules is to the influence of acute myocardial ischemia dog coronary flow and heart oxygen extraction ratio (M ± SD)
Before the index group ischemia behind ischemia 30 ' medicine behind 30 ' medicine behind 60 ' medicine 90 '
Normal group 70.6 ± 6.89 70.31 ± 7.01 70.8 ± 7.16 70.6 ± 7.03 70.4 ± 7.00
O
2E model group 68.79 ± 5.01 73.6 ± 4.74 72.47 ± 4.68 72.8 ± 4.87 72.1 ± 4.65
Heart oxygen small dose group 67.94 ± 5.78 71.6 ± 5.65 70.3 ± 5.43 69.2 ± 5.21 67.4 ± 5.17
The heavy dose of group of extraction ratio 67.71 ± 5.29 72.7 ± 5.01 70.8 ± 5.41 65.1 ± 5.13* Δ, 64.1 ± 5.07* Δs
(%) Radix Salviae Miltiorrhizae group 69.1 ± 5.81 72.8 ± 5.24 71.6 ± 5.15 67.4 ± 5.31 64.7 ± 5.06* Δs
Normal group 56.27 ± 4.33 55.44 ± 5.31 Δs, 54.29 ± 4.67 Δ Δs, 52.36 ± 4.78 Δ Δs, 51.89 ± 4.69 Δ Δs
Arteria coronaria model group 54.38 ± 6.39 47.21 ± 5.28 43.18 ± 5.03 40.15 ± 4.10 39.89 ± 4.11
Flow small dose group 53.69 ± 5.07 47.10 ± 6.08 45.39 ± 4.21 45.31 ± 4.69 44.96 ± 4.93
The heavy dose of group of CBF 54.69 ± 6.01 48.45 ± 5.66 47.23 ± 5.82 40.75 ± 5.71 Δ 40.98 ± 4.77 Δs
Ml/min Radix Salviae Miltiorrhizae group 52.87 ± 5.12 46.87 ± 5.06 47.34 ± 6.01 47.78 ± 5.48 Δs 46.41 ± 4.936
Table 5 Rhodiola rosea capsules is to the influence of acute myocardial ischemia dog heart gas and oxygen metabolism (M ± SD)
Before the index group ischemia behind ischemia 30 ' medicine behind 30 ' medicine behind 60 ' medicine 90 '
Normal group 6.31 ± 1.21 6.33 ± 1.25 6.31 ± 1.29 6.29 ± 1.26 6.29 ± 1.24
PV-aCO
2Model group 6.25 ± 1.26 7.50 ± 1.31 8.04 ± 1.26 8.09 ± 1.29 8.07 ± 1.28
Carbon dioxide small dose group 6.27 ± 1.24 7.43 ± 1.24 7.48 ± 1.21 7.51 ± 1.19 7.52 ± 1.16
The quiet moving heavy dose of group 6.28 ± 1.19 7.54 ± 1.31 7.52 ± 1.25 7.56 ± 1.27 7.49 ± 1.28 of dividing potential drop
Arteries and veins difference Radix Salviae Miltiorrhizae group 6.25 ± 1.23 7.47 ± 1.20 7.44 ± 1.31 7.51 ± 1.23 7.47 ± 1.25
Normal group 7.513 ± 0.089 7.536 ± 0.096 7.507 ± 0.104 Δ, 7.496 ± 0.097 Δ Δs, 7.494 ± 0.104 Δs
PHv model group 7.499 ± 0.106 7.448 ± 0.093 7.349 ± 0.103 7.306 ± 0.093*, 7.304 ± 0.094*
Small dose group 7.511 ± 0.098 7.454 ± 0.109 7.417 ± 0.098 7.421 ± 0.098 7.420 ± 0.106
Heavy dose of group 7.520 ± 0.110 7.418 ± 0.103 7.446 ± 0.107 7.457 ± 0.103 Δ 7.469 ± 0.110 Δs
Radix Salviae Miltiorrhizae group 7.501 ± 0.101 7.444 ± 0.109 7.437 ± 0.102 7.448 ± 0.096 Δ 7.439 ± 0.101
Embodiment 1:Method for making is got Radix Rhodiolae medical material 1100 grams, adds 8 times of water gagings and boils 1.5 hours, filters, and medicinal residues add 6 times of water gagings again and boiled 1.5 hours, filter, merge medicinal liquid twice, be condensed into extractum, get the about 190～200g of cream amount, relative density 1.2～1.25 (60 ℃ of mensuration) is got 1 part of extractum and is added 1.25～1.35 parts of mixings of starch, dry below 80 ℃, pulverize, with debita spissitudo ethanol system granule, oven dry, granulate, encapsulated, get 1000 of capsules, every heavy 0.38g is equivalent to crude drug 1.1g.
Embodiment 2:The embodiment of discrimination method gets the above-mentioned capsule 's content 1g that makes, and puts in the flask, adds the ethanol 30ml of 95% concentration, and reflux 1 hour is filtered, and filtrate is concentrated into dried, and residue adds ethanol 2ml makes dissolving, as need testing solution.Other gets the rhodioloside reference substance and adds ethanol and make the solution that every 1ml contains 1mg, product solution in contrast, according to 57 pages of thin layer chromatography (" one one of Pharmacopoeia of People's Republic of China nineteen ninety version ") appendix) test, draw various each 2～4 μ l of above-mentioned two kinds of solution, putting respectively in same and contain on the silica gel G thin layer that sodium carboxymethyl cellulose is a binding agent, is developing solvent with ethyl acetate-methanol-formic acid (9: 1: 0.8), launches, taking-up is dried, and spray is with 1%FeCl
3-1% potassium ferricyanide (1: 1) solution is put under the daylight and is inspected, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical blue mottle point.
Embodiment 3:The embodiment precision of content assaying method takes by weighing the about 2g of capsule 's content of above-mentioned preparation, put in the flask, add ethanol 30ml, reflux 1 hour is filtered, filtering residue is with 20ml washing with alcohol three times, merging filtrate also is concentrated into driedly to the greatest extent, and residue adds water 5ml makes dissolving, is added on polyamide column (80-120 order, the 5g dry column-packing, φ 1.5cm), water carries out eluting, accurately collects eluent 25ml, as need testing solution, draw reference substance solution and need testing solution 5--10 μ l, inject chromatograph of liquid, under the described condition of system suitability test, measure peak area, external standard method is calculated, promptly.
Claims (10)
1, a kind of medicine for the treatment of coronary heart disease it is characterized in that effective ingredient wherein is a rhodioloside, and the content in unit dose is no less than 0.8mg.
2, compositions according to claim 1 is characterized in that being made by the dry root and rhizome of Crassulaceae plant rhodiola kirilowii Regel Rhodiola Kirilowii.
3, a kind of method for preparing medicine according to claim 1 and 2 is characterized in that by any the carrying out in following a, b, three kinds of methods of c:
A. get 1100 parts of Radix Rhodiolae medical materials, add 8 times of water gagings and boiled 1.5 hours, filter, medicinal residues add 6 times of water gagings again and boiled 1.5 hours, filter, and merge medicinal liquid twice, be condensed into the extractum of relative density 1.2～1.25, get 1 part of extractum and add 1.25～1.35 parts of mixings of starch, dry below 80 ℃, pulverize, with debita spissitudo ethanol system granule, oven dry, granulate, encapsulated, or make tablet, granule; Or the food plant wet goods suspensoid that adds 1～3 part behind the above-mentioned extract dry made soft capsule;
B. get the Radix Rhodiolae medical material, adding 8 times of water gagings boiled 1.5 hours, filter, medicinal residues add 6 times of water gagings again and boiled 1.5 hours, filter, and merge medicinal liquid twice, concentrating under reduced pressure becomes 50 ℃ of relative density 1.05-1.07, add 95% alcoholic solution and make the alcohol amount of containing reach 50-70%, cold preservation was placed 20-26 hour, filtered, reclaim ethanol to there not being the alcohol flavor, and to be concentrated into 50 ℃ of following relative densities be 1.05-1.06, cooling, and thin up to each parts by volume medicinal liquid is equivalent to crude drug 0.44 weight portion, filter, the tween 80 of adding 0.1～0.15%, mixing is made oral liquid;
C. get Radix Rhodiolae medical material 40-60 weight portion, adding 8 times of water gagings boiled 1.5 hours, filter, medicinal residues add 6 times of water gagings again and boiled 1.5 hours, filter, and merge medicinal liquid twice, concentrating under reduced pressure becomes 50 ℃ of relative density 1.05-1.07, add 95% alcoholic solution and make the alcohol amount of containing reach 50-70%, cold preservation was placed 20-26 hour, filtered, reclaim ethanol to there not being the alcohol flavor, and to be concentrated into 50 ℃ of following relative densities be 1.05-1.06, adds 60～80 ℃ of water for injection 1000 parts by volume and stir, and makes dissolving, add sodium chloride 3～8 weight portions, transfer pH value to 6.0～6.5 with 40% sodium hydroxide solution, cooling is filtered, reuse 10000D molecular weight ultrafilter membrane, the following molecular weight ultrafilter membrane of 5000D classification ultrafiltration, added needle-use activated carbon 2～4 weight portion stirring and adsorbing 10～30 minutes, and filtered carbon removal, filtrate adds injection water to 1000 parts by volume, with serving as a contrast O.22m filtering with microporous membrane under the aseptic filter plate, the medicinal liquid packing, sterilization, promptly.
4, the method for preparing claim 1 or 2 described medicines is characterized in that making with the ethanol extraction Radix Rhodiolae of 30-70%.
5, the purposes of medicine according to claim 1 and 2 in the medicine of preparation treatment coronary heart disease.
6, differentiate the method for rhodioloside in the medicine, it is characterized in that: the thing of getting it filled is an amount of, or the taking liquid evaporate to dryness, extracts with an amount of heat of the ethanol of 70-100% concentration, filters, and makes need testing solution with extracting solution; Other gets the rhodioloside reference substance and adds ethanol and make solution in right amount, product solution in contrast, each is an amount of to draw above-mentioned two kinds of solution, point sample contains on the silica gel G thin layer that sodium carboxymethyl cellulose is a binding agent in same, with volume ratio is that ethyl acetate-methanol-formic acid mixed solvent of 9: 1: 0.8 is developing solvent, launch, dry, spray is with 1%FeCl
31: 1 solution of-1% potassium ferricyanide is put under the daylight and is inspected, in the test sample chromatograph, with the corresponding position of reference substance rhodioloside chromatograph on, show identical blue mottle point.
7, differentiate the method for claim 1 or 2 described medicines, it is characterized in that carrying out according to the following steps: thing 1g gets it filled, or the residue of the medicinal liquid evaporate to dryness gained of respective amount, the ethanol 30ml that adds 95% concentration, reflux 1 hour is filtered, and filtrate is concentrated into dried, residue adds ethanol 2ml makes dissolving, as need testing solution; Other gets the rhodioloside reference substance and adds ethanol and make the solution that every 1ml contains 1mg, product solution in contrast, test according to thin layer chromatography, draw each 2～4 μ l of above-mentioned two kinds of solution, putting respectively in same and contain on the silica gel G thin layer that sodium carboxymethyl cellulose is a binding agent, is that ethyl acetate-methanol-formic acid mixed solvent of 9: 1: 0.8 is developing solvent with volume ratio, launches, taking-up is dried, and spray is with 1%FeCl
3-1% potassium ferricyanide 1: l solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical blue mottle point.
8, measure the method for salidroside content in the medicine, it is characterized in that: it is an amount of that precision takes by weighing medicine, or get the medicinal liquid evaporate to dryness of respective amount, and the ethanol that adds 90-100% concentration is an amount of, and heat is extracted, extracting solution is concentrated into dried, residue is dissolved in water, and is added on the polyamide column water eluting, accurately collect the eluent certain volume, as need testing solution; Aqueous solution with the rhodioloside reference substance is a reference substance solution; Each is an amount of to draw reference substance solution and need testing solution, inject chromatograph of liquid, measure peak area, external standard method is calculated, promptly, condition determination is: with octadecylsilane chemically bonded silica is filler, volume ratio is that methanol-water-glacial acetic acid of 7: 93: 1 is a mobile phase, and flow velocity 0.9ml/min detects wavelength 276nm, 40 ℃ of column temperatures, theoretical cam curve calculate by the rhodioloside peak should be not less than 7000.
9, measure the method for salidroside content in claim 1 or the 2 described medicines, it is characterized in that carrying out according to the following steps: precision takes by weighing the about 2g of medicine, or gets the medicinal liquid evaporate to dryness of respective amount, put in the flask, add ethanol 30ml, reflux 1 hour, filter, filtering residue is with 20ml washing with alcohol three times, and merging filtrate also is concentrated into driedly to the greatest extent, and residue adds water 5ml makes dissolving, be added on the 80-120 order, diameter is on the polyamide column of 1.5cm, the water eluting is accurately collected eluent 25ml, as need testing solution; Precision takes by weighing the rhodioloside reference substance, is dissolved in water, and is settled to concentration for about 10mg/25ml, product solution in contrast; Draw reference substance solution and each 5--10 μ l of need testing solution, inject chromatograph of liquid, measure peak area, external standard method is calculated, promptly, condition determination is: with octadecylsilane chemically bonded silica is filler, with volume ratio is that methanol-water-glacial acetic acid mixed solvent of 7: 93: 1 is a mobile phase, and flow velocity 0.9ml/min detects wavelength 276nm, 40 ℃ of column temperatures, theoretical cam curve calculate by the rhodioloside peak should be not less than 7000.
10. according to the described method of arbitrary claim among the claim 6-9, it is characterized in that adopting the method for ultrasonic extraction medicine to replace wherein alcohol heat reflux or heat to extract medicine.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101357932B (en) * | 2008-09-12 | 2011-01-26 | 南京医科大学 | Separation method of salidroside and impurity therein and RP-HPLC analytical method of salidroside and impurity therein |
| CN101234136B (en) * | 2008-02-04 | 2011-06-22 | 赵红姝 | Medicament for curing diabetes retina affection |
| CN101281175B (en) * | 2007-06-12 | 2011-08-17 | 上海谱尼测试技术有限公司 | Method for measuring salidroside in food |
| CN101441201B (en) * | 2007-11-23 | 2011-10-05 | 上海雷允上药业有限公司 | Method for detecting contents of puerarin and rhodiola rosea glycosides in Paotianhongyangshejiu |
| CN103808819A (en) * | 2012-11-12 | 2014-05-21 | 江苏康缘药业股份有限公司 | Method for measuring contents of main components in rhodiola rosea medicinal material |
-
2003
- 2003-03-07 CN CN 03119286 patent/CN1283257C/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101281175B (en) * | 2007-06-12 | 2011-08-17 | 上海谱尼测试技术有限公司 | Method for measuring salidroside in food |
| CN101441201B (en) * | 2007-11-23 | 2011-10-05 | 上海雷允上药业有限公司 | Method for detecting contents of puerarin and rhodiola rosea glycosides in Paotianhongyangshejiu |
| CN101234136B (en) * | 2008-02-04 | 2011-06-22 | 赵红姝 | Medicament for curing diabetes retina affection |
| CN101357932B (en) * | 2008-09-12 | 2011-01-26 | 南京医科大学 | Separation method of salidroside and impurity therein and RP-HPLC analytical method of salidroside and impurity therein |
| CN103808819A (en) * | 2012-11-12 | 2014-05-21 | 江苏康缘药业股份有限公司 | Method for measuring contents of main components in rhodiola rosea medicinal material |
| CN103808819B (en) * | 2012-11-12 | 2015-05-20 | 江苏康缘药业股份有限公司 | Method for measuring contents of main components in rhodiola rosea medicinal material |
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