CN1552723A - Liaodong oak leaf saponin and its medicinal composition - Google Patents
Liaodong oak leaf saponin and its medicinal composition Download PDFInfo
- Publication number
- CN1552723A CN1552723A CNA2003101099374A CN200310109937A CN1552723A CN 1552723 A CN1552723 A CN 1552723A CN A2003101099374 A CNA2003101099374 A CN A2003101099374A CN 200310109937 A CN200310109937 A CN 200310109937A CN 1552723 A CN1552723 A CN 1552723A
- Authority
- CN
- China
- Prior art keywords
- aralia wood
- saponin
- liao
- leaf
- glucopyranose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An arakoside prepared from Liaodong aralia chinensis's leaf, its medical composition containing the arakoside as its main component, its preparing process, and its application in preventing and treating the deficiency of myocardial function are disclosed.
Description
Invention field
The present invention relates to Liao Dong Aralia wood leaf total saponins and pharmaceutical composition thereof, particularly relating to Liao Dong Aralia wood leaf total saponins is the pharmaceutical composition of primary activity composition, its preparation method and the application that is used for preventing and treat the related pathologies condition of heart failure and myocardial ischemia in production.
Background of invention
Liao Dong Aralia wood another name Aralia mandshurica is commonly called as Root-bark of Japanese Aralia, is Wu Jia Ke Aralia fogfruit (Aralia elata (Miq.) Seem).Border, filling order clump and the river valley area of this plant-growth below height above sea level 1000m.In China, Liao Dong Aralia wood mainly is distributed in three provinces in the northeast of China's Eastern Mountain Area, and wherein only Jilin Province prolongs border district district standing stock and can reach more than 3000 ton.Ancient Chinese is used as medicine for root, root white skin and the leaf of Jiu Yi Aralia wood.The former Russian scholar found once that congener such as distant eastern Aralia wood had the effect of " adaptogen " sample, clinically as tonic invigorator and central nervous system stimulant.Be used for the treatment of illnesss such as psychasthenia, rheumatic arthritis, hepatitis, diabetes, stomach spasm, constipation, deficiency of kidney-QI clinically.In addition, the Oleanolic Acid that has the people from this platymiscium, to extract, and used as the hepatitis treatment medicine.
Since the 1950's, obtained remarkable progress about Liao Dong Aralia wood root skin, bark, leaf and the chemical ingredients of tender shoots and the research of pharmacological activity thereof, and wherein mainly concentrated on the research of saponin component.For example, people such as H.K.kohetkoy separates in the hot methanol extract of Liao Dong Aralia wood and obtains three kinds of saponin(es (Ming Ming Wei Aralia wood saponin A, B and C respectively) (Araloside A, B, C).Through identifying that the aglycon of three kinds of saponin(es is Oleanolic Acid (kochetkoy, et al.Dokl Akad Nauk, 1963; 150 (6): 1289).Continue after, Dzhunibaeva T. has isolated seven kinds of saponin(es with the method for silica gel column chromatography from the leaf of Liao Dong Aralia wood, and these saponin(es are all done as aglycon with Oleanolic Acid.People such as Jiang Yongtao and Xu Suixu gets eight kinds of compounds from the root skin of the eastern Aralia wood of the Liao Dynasty.People such as Yang Guohong and Zhou Jian isolates 6 kinds of monomeric compounds (Yang Guohong, herbal medicine, 1995 from the leaf of the eastern Aralia wood of the Liao Dynasty; 26 (10): 514).In addition, people such as the few river of Song isolates at least 7 kinds of triterpenoid saponins (Song Shaojiang, Li Jinghong etc., Chinese pharmaceutical chemistry magazine, 2000 from the root skin of the eastern Aralia wood of the Liao Dynasty in recent years; 10 (4): 296; Song Shaojiang, Lu Liming etc., Shenyang Pharmaceutical University's journal, 2001; 18 (6): 462) (Shao-JiangSong, Norio Nakamura, Chao-Mei Ma, et al.Five saponins from the root barkof Aralia elata[J] .Phytochemistry 56 (2001) 491-497).
Though some reports about the fundamental research of Liao Dong Aralia wood saponin(e were once arranged in the past, but traditional positions such as the root skin that these work mainly are to use Liao Dong Aralia wood and bark are separated and are extracted indivedual saponin monomers, and the active research of related biological also mainly is at antitumor (for example referring to Chinese patent application publication number 1184641), anti-inflammatory, anti-hypoxia and suppresses aspects such as transformation reactions and oneself immune response.Particularly, so far still not about Guan Dong Aralia wood leaf total saponins being developed to the report of cardiac drug.On the basis of a large amount of laboratory studyes that we are former, for the first time successfully prepared and to have met the clinical application requirement fully, with Liao Dong Aralia wood leaf total saponins is the primary activity composition, be used for the treatment of the pharmaceutical composition of the related pathologies condition that is caused with prophylaxis of heart failure and myocardial ischemia, thereby finished the present invention.
The purpose of invention
An object of the present invention is to provide and comprise and be selected from Liao Dong Aralia wood saponin(e V, VII, X Aralia wood leaf saponin A (1) Aralia wood leaf saponin(e B (2), Hederagenin-3-O-β-D-Glucopyranose-(1 → 3)-β-D-galactopyranoside, Hederagenin-3-O-β-D-Glucopyranose-(1 → 3)-α-l-arabopyranose-28-O-β-D-glucopyranosyl ester glycosides, Oleanolic Acid-3-O-β-D-Glucopyranose-28-O-β-D-glucopyranosyl ester glycosides, Quercetin-3-O-β-l-pyrans rhamnoside, Oleanolic Acid-3-O-β-D-galactopyranose-28-O-β-D-glucopyranosyl ester glycosides, the distant eastern Aralia wood total saponins of at least ten one kinds of monomer components of Oleanolic Acid-3-O-β-D-Glucopyranose (1 → 3)-β-D-glucopyranoside.
This purpose preferred embodiment according to the present invention is to extract in the leaf by Liao Dong Aralia wood plant as said Liao Dong Aralia wood total saponins wherein.
Another object of the present invention provides the method for producing the Liao Dong Aralia wood leaf total saponin extracts that is defined as above, and is characterised in that comprising the use macroporous adsorbent resin and separates, and use Zeo-karb and decolorizing resin purifying Liao Dong Aralia wood leaf total saponins.
It is the primary activity composition that a further object of the present invention provides Liao Dong Aralia wood leaf total saponins, and contains the pharmaceutical composition of one or more pharmaceutically acceptable carriers or vehicle.
This purpose preferred embodiment according to the present invention, wherein as the Liao Dong Aralia of primary activity composition in pharmaceutical composition wood leaf total saponins by being selected from Liao Dong Aralia wood saponin(e V, VII, X Aralia wood leaf saponin A (1) Aralia wood leaf saponin(e B (2), Hederagenin-3-O-β-D-Glucopyranose-(1 → 3)-β-D-galactopyranoside, Hederagenin-3-O-β-D-Glucopyranose-(1 → 3)-α-l-arabopyranose-28-O-β-D-glucopyranosyl ester glycosides, Oleanolic Acid-3-O-β-D-Glucopyranose-28-O-β-D-glucopyranosyl ester glycosides, Quercetin-3-O-β-l-pyrans rhamnoside, Oleanolic Acid-3-O-β-D-galactopyranose-28-O-β-D-glucopyranosyl ester glycosides, at least ten one kinds of monomer components of Oleanolic Acid-3-O-β-D-Glucopyranose (1 → 3)-β-D-glucopyranoside are formed.
It is the method for the pharmaceutical composition of primary activity composition with Liao Dong Aralia wood leaf total saponins that a further object of the present invention provides production, and this method comprises:
(1) provides Liao Dong Aralia wood leaf total saponins;
(2) step (1) being obtained Liao Dong Aralia wood leaf total saponins mixes mutually with one or more pharmaceutically acceptable carriers and/or vehicle.
This purpose preferred embodiment according to the present invention can add in addition also in the wherein said pharmaceutical composition that one or more are natural or chemosynthesis, with primary activity composition Liao Dong Aralia wood leaf total saponins auxiliary or synergistic other activeconstituentss are arranged.
The pharmaceutical composition that it is the primary activity composition that a further object of the present invention provides with the wooden leaf total saponins of Liao Dong Aralia is used for preventing and treating the application of heart failure and myocardial ischemia related pathologies condition in production.
This purpose preferred embodiment according to the present invention, wherein said cardiac insufficiency relative disease comprises the heart failure that a variety of causes causes.
The particular content of invention
The invention provides the total saponins and the pharmaceutical composition thereof that separate and extract by in the Liao Dong Aralia wood leaf, particularly providing with the Liao Dynasty's eastern Aralia wood leaf total saponins is the pharmaceutical composition of primary activity composition, its preparation method with and be used for preventing and treating the application of human or animal's heart failure and myocardial ischemia related pathologies condition in production.
In order to obtain pharmaceutical composition of the present invention, must at first prepare Liao Dong Aralia wood leaf total saponins.The inventor discovers, the very soluble in water and methyl alcohol of Liao Dong Aralia wood leaf total saponins, the organic solvent that the ethanol isopolarity is bigger, but be insoluble in the little organic solvent of chloroform isopolarity.According to this chemical property, we utilize the method for setting up ourselves, separate and extract obtaining at least ten one kinds of compounds with triterpenoid saponin structure from the Liao Dynasty's eastern Aralia wood leaf.The aglucon of these compounds (aglycon) is Oleanolic Acid and ivy, and glycosyl part then is to be combined on the C-3 hydroxyl and C-28 carboxyl of aglucon by glycosidic link and ester glycosidic bond.
Though can be from any pharmaceutically acceptable part of Liao Dong Aralia wood; for example separate in the root of plant, root skin, bark, stem, leaf and the tender shoots and obtain Liao Dong Aralia wood leaf total saponins; but under the situation of a large amount of these materials of collection; the destruction of natural resource usually can be caused as material source in traditional positions such as the root of use plant, root skin, bark.Therefore, in order to prevent the destruction of resource, the special Liao of use Dong Aralia wood leaf is as the material source that extracts total saponins among the present invention.
In order to obtain Liao Dong Aralia wood leaf total saponins, can adopt water-boiling method to extract prewashed Liao Dong Aralia wood leaf, collect extracting solution then and to the milk of lime that wherein adds appropriate amount, to remove impurity such as flavones and tannin; Filtering and collecting filter liquid is crossed macroporous adsorbent resin (for example AB8, D4020, D101, M130 etc.) post.Water elution is colourless to effluent liquid, to remove impurity such as carbohydrate in the filtrate and protein.Then, with ethanol (50%～95%) wash-out resin, elute with the compositions such as total saponins that will be adsorbed onto resin column.Collect elutriant and the further cation exchange resin column of crossing then, to remove anionic impurity.Make this elutriant cross decolorizing resin (as anionite-exchange resin such as D941) post at last again,, obtain the white powder product of purity after the drying about the wooden total saponins of the Liao Dong Aralia 80% or more to remove impurity such as pigment and to make the end product decolouring.
With the method for usually using inflammable toxic liquids such as ether, chloroform, ethyl acetate as organic solvent in the prior art (referring to Qi Fengxiang etc. Heilungkiang medicine; 1997; 5 (10): 284; Yang Guohong. herbal medicine; 1995; 10 (26); Chinese patent application publication number 1184641) difference, the principal character of the inventive method are, not only use Liao Dong Aralia wood leaf as material source, and wherein employed organic flux also are relatively stable and safe ethanol.Therefore, compared with prior art, method of the present invention greatly reduces production cost, has reduced the destruction of natural resources and the pollution of environment, and is particularly suitable for the large-scale industrial production of product.
In addition, method of the present invention is also first with the separation and purification in Liao Dong Aralia wood leaf total saponins of macroporous adsorbent resin, ion exchange resin and decolorizing resin chromatography combined utilization.
Use mass spectrum (MS), infrared spectra (IR), nucleus magnetic resonance (
1H-NMR and
13Detection method such as C-NMR), at least ten one kinds of compounds that thin-layer chromatography is separated to carry out the structure evaluation, the result shows that compound all has the big heterocycle structure of triterpenoid saponin, wherein aglucon is respectively Oleanolic Acid or hederagenin, glycosyl comprises glucose, rhamnosyl and pectinose, and these glycosyls are attached on the C-3 hydroxyl and C-28 carboxyl of aglucon by glycosidic link and/or ester glycosidic bond respectively.
Therefore, according to the preferred embodiments of the invention, wherein said Liao Dong Aralia wood leaf total saponins accounts for more than 80% (w/w) of said pharmaceutical composition, and said Liao Dong Aralia wood leaf total saponins comprises Liao Dong Aralia wood saponin(e V at least, VII, X Aralia wood leaf saponin A (1) Aralia wood leaf saponin(e B (2), Hederagenin-3-O-β-D-Glucopyranose-(1 → 3)-β-D-galactopyranoside, Hederagenin-3-O-β-D-Glucopyranose-(1 → 3)-α-l-arabopyranose-28-O-β-D-glucopyranosyl ester glycosides, Oleanolic Acid-3-O-β-D-Glucopyranose-28-O-β-D-glucopyranosyl ester glycosides, Quercetin-3-O-β-l-pyrans rhamnoside, Oleanolic Acid-3-O-β-D-galactopyranose-28-O-β-D-glucopyranosyl ester glycosides, at least ten one kinds of monomer components of Oleanolic Acid-3-O-β-D-Glucopyranose (1 → 3)-β-D-glucopyranoside.This shows, with wooden this Liao Dong Aralia wood plant over-ground part that usually is regarded as waste of leaf of withered and yellow preceding Liao Dong Aralia in autumn is raw material, can use relatively simple extraction process, produce the Liao Dong Aralia wood leaf total saponin extracts that purity reaches 80% (w/w) approximately.
Can separately or unite use is suitable for clinical application by the Liao Dong Aralia wood leaf total saponins preparation of the inventive method separation and extraction pharmaceutical composition.For example, can be according to known method in the pharmaceutical industry (as referring to Remington ' s Pharmaceutical Science.15
ThEd., Mack PublishingCompany, 1980) Liao Dong Aralia of the present invention wood leaf total saponins and one or more pharmaceutically acceptable carriers or vehicle or thinner are mixed by proper proportion, and by making pharmaceutical composition of the present invention after the currently known methods degerming.
According to the difference of route of administration, pharmaceutical composition of the present invention can be mixed be suitable in intravenously, intramuscular, the body cavity, in the tissue, the injectable solution or the dispersion agent of intracutaneous or subcutaneous administration; Or be suitable for powder agent, tablet, granule, pill, emulsion, the capsule of oral administration; Or be suitable for topical and sprays, gelifying agent, lozenge or suppository by skin or mucosal absorption administration.
In order to prepare the injectable solutions that is suitable for the outer administration of gi tract, for example can use sterile distilled water, water for injection, isotonic sodium chloride or glucose solution, or lower concentration phosphate buffered saline (PBS) (PBS) and contain the solvent of ethanol, polyvalent alcohol (as ethylene glycol, propylene glycol and liquid polyethylene glycol etc.) or dispersion medium as carrier or thinner.Under any circumstance, said injectable formulation all should be aseptic and can flow and be suitable for by the injector to inject administration.In addition, under production, transportation and condition of storage, said preparation also must be stable, and can be to microbiological contamination such as antibacterium and fungies.In case of necessity, can add antioxidant (as anti-bad hydrochloric acid), microbiotic (as penicillin and Streptomycin sulphate or other anti-mycotic agents) and sanitas (as Sodium Benzoate, degree rice phenol, Sorbic Acid etc.), and solubilizing agent and the tensio-active agent that is used for keeping the required granular size of dispersion agent.
For example, can be at first the Liao Dong Aralia wood leaf total saponins powder 100g that accurately takes by weighing be dissolved among the water for injection 2000ml and with gained solution and be transferred to pH=6.5～7.5.Then, and adding activated carbon 6g in gained solution (0.3%, w/v), and in boiling water bath, heated 10～15 minutes.Conventional filtration is also with after the 0.02 μ filtering with microporous membrane degerming, and promptly making can be for the Liao Dong Aralia wood leaf total saponins aqueous solution of intramuscular or intravenous injection administration.
The Liao Dong Aralia wood leaf total saponins powder 100g and the N.F,USP MANNITOL 80g that accurately take by weighing are dissolved among the water for injection 2000ml.Adding activated carbon 6g in gained solution (0.3%, w/v), and in boiling water bath, heated 10～15 minutes.Conventional filtration is also with 0.02 μ filtering with microporous membrane, and promptly making after packing and the lyophilize can be for the Liao Dong Aralia wood leaf total saponins powder pin of intramuscular or intravenous injection administration.
In order to prepare tablet, powder agent, capsule, granule or the emulsion that is suitable for oral administration, can use disaccharides such as sucrose, lactose, semi-lactosi, or six carbon polyhydroxy-alcohols such as N.F,USP MANNITOL, sorbyl alcohol, and W-Gum, gelatin, lipid, Microcrystalline Cellulose etc. are as carrier or vehicle.In case of necessity, also can in these oral preparations, add disintegrating agent, lubricant, tinting material, sweeting agent, spices, dispersion agent and tensio-active agent.
In addition, also can use known method and auxiliary composition in the pharmaceutical industry, pharmaceutical composition of the present invention is made microcapsule or liposome agent.
The pharmaceutical composition that the present invention further provides the said Liao of containing Dong Aralia wood leaf total saponins is in treatment or prevent the particularly application in the heart failure of myocardium related pathologies condition.
For this reason, the experimental animal model for heart failure that we utilize vetanarcol to bring out has been observed the pharmaceutical composition that serves as basic or activeconstituents with the wooden leaf total saponins of east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion of the present invention to blood pressure and the working heart hemodynamic influence of rat behind the force failure of body-centered.
General pharmacology is learned and pharmacodynamic experiment shows, pharmaceutical composition of the present invention is to activity and the not obviously influence of behavior of animal (mouse, rat and dog).But pharmaceutical composition of the present invention then has tangible rising effect to the blood pressure of the experimental animal in heart failure that vetanarcol bring out.For example, give experimental dog intravenous injection in heart failure pharmaceutical composition of the present invention (1.4mg/kg), the blood pressure of animal is obviously raise, and can keep and reach more than 180 minutes.This result is similar to the effect of positive control medicine Deslanoside.
On this basis, we have carried out many index observings with regard to pharmaceutical composition of the present invention to the Hemodynamics of experimental animal in heart failure (dog and rat) especially.Wherein with physiological saline as negative control, and with Deslanoside as the positive control medicine.Change as can be seen from every index of heart function, behind the intravenous injection pharmaceutical composition of the present invention, the every index of animal heart function significantly improves, and its effect is similar to cardiac glycoside medicine Deslanoside, points out pharmaceutical composition of the present invention to have good heart failure resistance effect.For example, our experimental result shows that pharmaceutical composition of the present invention can improve the left ventricular pressure (LVSP) of animal significantly, improves maximum the rate of change (± dp/dt of left ventricular pressure
Max), and heart output (CO), cardiac output (SV), and cardiac index (CI) and heartbeat index (SI).Above-mentioned these results are also similar to the effect of positive control medicine Deslanoside.
In addition, our experimental result also shows, the Liao Dong Aralia wood leaf total saponins of various dose is different to hemodynamic effect, and along with the increase of the wooden leaf saponin content of Liao Dong Aralia, the also corresponding rising of every hemodynamic index, thus demonstrate certain docs-effect dependence.
Pharmaceutical composition of the present invention is applicable to prevention and the treatment various diseases relevant with myocardial ischemia in heart failure, these diseases or pathological conditions comprise but are not only limited to for example because of congenital heart disease, valvular heart disease, cor pulmonale, coronary atherosclerotic heart disease, hypertensive heart disease, infectivity and non-infectious myocarditis, disseminated intravascular coagulation, whole body severe infection, and the heart failure that causes such as hemorrhagic shock, and the myocardial ischemia that causes of reason such as coronary vasodilator cycle penalty.
Difference according to application target, pharmaceutical composition of the present invention is except that the Liao Dong Aralia wood leaf total saponins that contains as the primary activity composition, also can contain one or more have identical, similar or different biological active, and to the existing auxiliary or synergy of primary activity component list, but mutual again each other not natural or synthetic other drug composition or its mixture of antagonism.
According to the present invention, said other activeconstituentss comprise but be not only limited to natural origin or synthetic cardiotonic drug (as noradrenalin, digitalin etc.), coronary vasodilator (as Nitrates preparation, calcium ion antagonist etc.), hypotensive agent (as beta receptor hold back agent, diuretic(s), angiotensin converting enzyme inhibitor etc.), anti-infection agent (as penicillin, Streptomycin sulphate etc.).
In general, the oral administration dosage of pharmaceutical composition of the present invention is 0.5-50mg/kg/ days, is preferably 1-20mg/kg/ days; Muscle or intravenous injection dosage are 0.1-20mg/kg/ days, are preferably 0.5-10mg/kg/ days.Certainly, definite dosage should be according to character, severity, patient's age, body weight, the general health state of illness to be treated or pathological state, and patient is determined by the clinician according to the principle of individuation the factors such as susceptibility, tolerance and administering mode of used medicine.
The following example is intended to further describe rather than limit by any way for example the present invention.Under the prerequisite that does not deviate from the spirit and principles in the present invention, any change or change that those of ordinary skills that the present invention did are realized easily all will fall within the claim scope that awaits the reply of the present invention.
Embodiment
The preparation (1) of embodiment 1 Liao Dong Aralia wood leaf total saponin extracts
Take by weighing dry Liao Dong Aralia wood leaf 1kg, clean and smash to pieces the back to the water that wherein adds about 13 times of volumes.Soak 2 hours post-heating and boiled about 2.5 hours, filter, and twice of boiling again.Wherein amount of water is followed successively by 10,8 times of medicinal material weight, and decocting time was followed successively by 2.0,1.5 hours.Merge decoction liquor then, and add milk of lime regulator solution pH value to 11.Placed 12～24 hours, and after the filtration, filtrate slowly injected pretreated AB8 type macroporous adsorbent resin (2kg) post, and water to be eluted to effluent liquid colourless.Discard water elution liquid, use 80% ethanol elution colourless again to effluent liquid.Descend strongly acidic styrene's Zeo-karb 001*7 (732) [Hydrogen] resin (0.1kg) post in room temperature then, and used 95% ethanol elution.Effluent liquid is after D941 type macroporous weakly basic anion exchange resin (0.3kg) post, and uses 95% ethanol elution.Collect elutriant then, concentrating under reduced pressure and reclaim ethanol after, obtain exsiccant Liao Dong Aralia wood leaf total saponins 32g (yield 3.2%).
The preparation (2) of embodiment 2: Liao Dong Aralias wood leaf total saponin extracts
Take by weighing dry Liao Dong Aralia wood leaf 1kg, clean and smash to pieces the back to the water that wherein adds about 13 times of volumes.Soak 2 hours post-heating and boiled about 2.5 hours, twice of boiling (amount of water is followed successively by 10,8 times of medicinal material weight, and decocting time was followed successively by 2.0,1.5 hours) again after the filtration.Merge decoction liquor then, and add the pH value to 11 of milk of lime regulator solution.Placed 12～24 hours, and after the filtration, filtrate slowly injected pretreated D4020 type macroporous adsorbent resin (2kg) post, and water to be eluted to effluent liquid colourless.Discard water elution liquid, use 85% ethanol elution colourless again to effluent liquid.Descend strongly acidic styrene's Zeo-karb 001*7 (732) [Hydrogen] resin (0.1kg) post in room temperature then, and used 95% ethanol elution.Effluent liquid is after D941 type macroporous weakly basic anion exchange resin (0.3kg) post, and uses 95% ethanol elution.Collect elutriant then, concentrating under reduced pressure and reclaim ethanol after, obtain exsiccant east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion wood leaf total saponins 31g (yield 3.1%).
Embodiment 3: pharmaceutical composition of the present invention is to the hemodynamic influence of model dog in heart failure
Present embodiment explanation the present invention is that the pharmaceutical composition of primary activity composition is to experimental dog heart function in heart failure and hemodynamic influence with east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion wood leaf total saponins.
30 of the male and female hybrid dogs of the about 13-17kg of body weight are divided into five groups at random, six every group.After Sodital sodium solution (30mg/kg) intravenous injection anesthesia, conventional promoting the circulation of qi cannula also connects electric pulmotor (respiratory capacity 3-4kpa); Separate right carotid and insert blood pressure measuring device; The constant speed infusion pump that separates external jugular vein, intubate and connection transfusion usefulness.Then, the 4th intercostal is opened chest in the left side, cuts off pericardium and separates aortic root, inserts the magnetic flow meter probe with record cardiac output (CO).Separate right common femoral artery simultaneously, carry out left ventricular cannulation in order to measuring and record left ventricular pressure (LVSP) (signal amplifies 10 times through direct-current amplifier) and left ventricular end diastolic presssure (LVEDP) (Kpa).LVSP electrical signal input differentiator is traced the dp/dt curve, and record the maximum rate of change (± dp/dt max) (Kpa/ second) of left ventricular pressure from the dp/dt curve.Animal foot connects electrocardioelectrode, and record mark II lead electrocardiogram (ECG) is used heart rate instrumentation centering rate (HR) simultaneously.Above-mentioned each heart function and hemodynamic parameter all are recorded on the polygraph simultaneously.
After finishing operation and stablizing ten minutes, above-mentioned every heart function and hemodynamic parameter before the record animal-use drug.Before the experiment, all animals are all imported 3% Sodital sodium solution through the vein constant speed, to cause model in heart failure (with animal aorta mean blood pressure (MBP) decline 40-50%, ± dp/dtmax descends more than 70% as indication in heart failure).Then, negative control group and the positive control treated animal difference isopyknic physiological saline of intravenous injection or Deslanoside injection liquid (0.015mg/kg) (Wuxi City the 7th pharmaceutical factory produces, lot number 990801).The animal of three experimental group is then distinguished intravenous injection low dose (1.4mg/kg), middle dosage (2.8mg/kg) and heavy dose of (5.6mg/kg) pharmaceutical composition of the present invention.
Respectively at after the administration 5,30,60, detected and write down the above-mentioned hemodynamic parameter of each treated animal in 120,180 and 240 minutes.The following tabulation 1 of experimental result is to shown in the table 3.
Table 1 pharmaceutical composition of the present invention (injection liquid) is to the influence of the blood pressure of heart failure model dog (X ± SD)
| Group (n=6) | Before the administration | After the administration (minute) | ||||
| ??5 | ????30 | ????60 | ????180 | ????240 | ||
| Negative control group | ??4.95± ????1.180 | ??5.24± ????0.710 | ????5.422± ????????1.096 | ????5.86± ????????1.403 | ????6.06± ????????1.640 | ????5.97± ????????1.659 |
| Positive controls | ??5.58± ?????0.519 | ??5.93± ????0.881 | ????6.87± ????????0.791 * | ????7.38± ????????0.745 * | ????7.71± ????????1.157 | ????7.69± ????????1.082 |
| Experimental group (low dose) | ??5.42± ??????1.336 | ??5.45± ????0.972 | ????6.75± ????????0.610 * | ????7.66± ????????1.259 * | ????7.98± ????????1.563 | ????7.85± ????????1.730 |
| (middle dosage) | ??5.24± ????0.987 | ??6.00± ????0.828 | ????7.31± ????????0.933 ** | ????8.49± ????????1.039 ** | ????7.86± ????????1.432 | ????7.68± ????????1.336 |
| (heavy dose) | ??5.46± ????0.607 | ??6.02± ????0.753 | ????7.88± ????????1.086 ** | ????9.25± ????????1.870 ** | ????9.14± ????????2.4048 * | ????7.96± ????????1.561 |
Compare with negative control group:
*P＜0.05,
*P＜0.01.
Table 2 medicine composition injection of the present invention is to the influence of the maximum rate of change of left ventricular pressure (Kpa/ second) (X ± SD)
| Group (n=6) | Before the administration | After the administration (minute) | ||||
| ????5 | ????30 | ??60 | ??180 | ????240 | ||
| Negative control group | ??131.08± ????21.356 | ????15.07± ????????10.884 | ????162.18± ????????30.880 | ??179.96± ??????63.510 | ??171.07± ??????56.187 | ????168.85± ????????64.021 |
| Positive controls | ??137.74± ????6.884 | ????153.30± ????????7.301 | ????191.06± ????????26.212 | ??248.83± ??????41.014 * | ??239.94± ??????40.432 * | ????237.72± ????????45.725 |
| Experimental group (low dose) | ??124.41± ????20.069 | ????151.07± ????????10.884 | ????182.18± ????????31.167 | ??251.05± ??????40.796 * | ??242.16± ??????56.187 | ????237.72± ????????48.000 |
| Experimental group (low dose) | ??122.19± ????13.106 | ????151.07± ????????21.768 | ????206.62± ????????23.470 * | ??253.27± ??????26.660 * | ??246.61± ??????44.411 * | ????237.72± ????????47.254 |
| Experimental group (low dose) | ??155.52± ????18.212 | ????171.07± ????????19.621 | ????246.61± ????????37.467 ** | ??284.48± ??????46.687 ** | ??286.60± ??????35.519 ** | ????228.83± ????????25.871 |
Compare with negative control group:
*P＜0.05,
*P＜0.01,
* *P＜0.001.
Table 3 pharmaceutical composition of the present invention is to the influence of the left chamber end-diastolic pressure (kPa) of model dog in heart failure (X ± SD)
| Group (n=6) | Before the administration | After the administration (branch) | ||||
| ??5 | ??30 | ??60 | ??180 | ??240 | ||
| Negative control group | ??0.29± ????0.260 | ??0.20± ????0.184 | ??0.25± ????0.132 | ??0.22± ????0.182 | ??0.22± ????0.139 | ??0.19±0.162 |
| Positive controls | ??0.11± ????0.330 | ??0.02± ????0.308 | ??0.05± ????0.299 | ??0.02± ????0.354 | ??0.02± ????0.297 | ??0.11±0.260 |
| Experimental group (low dose) | ??0.29± ????0.196 | ??0.29± ????0.231 | ??0.27± ????0.303 | ??0.27± ????0.315 | ??0.31± ????0.311 | ??0.25±0.232 |
| Experimental group (middle dosage) | ??0.27± ????0.121 | ??0.31± ????0.203 | ??0.29± ????0.053 | ??0.29± ????0.176 | ??0.27± ????0.188 | ??0.29±0.176 |
| Experimental group (heavy dose) | ??0.07± ????0.200 | ??0.16± ????0.196 | ??0.16± ????0.196 | ??0.09± ????0.276 | ??0.02± ????0.246 | ??0.02±0.258 |
After vetanarcol were made and declined as can be seen from the table, the dog heart function obviously descended, and was contrast with the every cardiac functional parameter after the heart failure.Behind the intravenous injection physiological saline, heart function does not have obvious change, and behind the intravenous injection east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion wood leaf total saponins, heart function significantly improves.Proof east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion wood middle period total saponins has the heart failure resistance effect, and its effect is similar to known cardiac glycoside medicine Deslanoside.
Embodiment 4: pharmaceutical composition of the present invention is to the hemodynamic influence of rat model in heart failure
Present embodiment explanation the present invention is that the pharmaceutical composition of primary activity composition is to experimental rat heart function in heart failure and hemodynamic influence with east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion wood leaf total saponins.
With 50 of the Wistar rats of the about 250-320g of body weight, be divided into five groups at random, 10 every group.Warp
Behind abdominal injection 20% urethanum (1.2g/kg) anesthetized animal, separate right carotid, the row left ventricular cannulation detects and the record cardiac functional parameter; Separate the parallel intra-arterial intubate of right common femoral artery, the record arteriotony changes; Separate homonymy femoral vein row vein intubate simultaneously, set up route of administration.The non-insertion end of ventricle intubate and arterial cannulation is led physiograph with four and microcomputer links to each other by transverter, monitor and write down left ventricular systolic pressure (LVSP) synchronously, left chamber is maximum rises and fall off rate (± dp/dt
Max), last (LVEDP), systolic pressure (SAP), diastolic pressure (DAP) and the heart rate (HR) of pressing relaxes in left chamber.
After finishing operation and stablizing ten minutes, above-mentioned every heart function and hemodynamic parameter before the record animal-use drug.Before the experiment, all animals are all imported 3% Sodital sodium solution through the vein constant speed, to cause model in heart failure (with animal aorta mean blood pressure (MBP) decline 40-50%, ± dp/dtmax descends more than 40% as indication in heart failure).Then, negative control group and the positive control treated animal difference isopyknic physiological saline of intravenous injection or Deslanoside injection liquid (0.015mg/kg) (Wuxi City the 7th pharmaceutical factory produces, lot number 990801).Experimental group intravenous injection pharmaceutical composition 10mg/kg of the present invention.
Respectively at after the administration 5,10,20, detected and write down the above-mentioned hemodynamic parameter of each treated animal in 30 minutes.The following tabulation 4 of experimental result is to shown in the table 10.
Table 4. pharmaceutical composition of the present invention to rat in heart failure at the influence of body running systolic pressure (kPa) (X ± SD)
| Behind the preceding heart failure of group heart failure | After the administration (minute) |
| ??5?????????????10?????????????20????????????30 | |
| Negative control group 14.7 ± 1.4*** 9.3 ± 1.0 experimental group 14.5 ± 1.7 ***7.7 ± 1.6 positive drug groups 14.8 ± 1.9 ***???8.7±1.4 | ??9.6±1.1??????9.1±1.0???????8.7±1.3??????9.1±1.1 ??9.4±1.8 *????10.0±1.8 **???10.8±1.5 **??10.6±1.3 **??10.1±1.4 *???10.7±1.5 **???10.5±1.4 *???10.6±1.1 ** |
With comparison before the administration,
*P＜0.05,
*P＜0.01,
* *P＜0.001
Table 5. pharmaceutical composition of the present invention is pressed the influence (X ± SD) of (kPa) at the body running diastole to rat
| Behind the preceding heart failure of group heart failure | After the administration (minute) |
| ??5???????????10??????????20??????????30 | |
| Negative control group 10.3 ± 1.7 ***6.3 ± 1.3 experimental group 8.8 ± 1.2 ***6.3 ± 1.0 positive drug groups 8.6 ± 1.4 ***???6.1±1.1 | ??5.9±1.0????6.2±1.3????6.2±1.2????5.8±1.0 ??6.9±1.1????7.0±0.9????7.0±0.8????7.1±0.9 ??6.6±1.1????6.7±1.0????6.7±0.9????6.7±0.8 |
With comparison before the administration,
*P＜0.05,
*P＜0.01,
* *P＜0.001
Table 6 pharmaceutical composition of the present invention to rat at the influence of the maximum climbing speed of body running heart left chamber (kPa/s) (X ± SD)
| Behind the preceding heart failure of group heart failure | After the administration |
| ??5????????????10???????????20????????????30 | |
| Negative control group 385 ± 46 ***146 ± 18 experimental group 423 ± 63 ***163 ± 24 positive drug groups 373 ± 46 ***???144±26 | ??145±16??????148±22??????148±18???????145±20 ??241±49 ***??261±56 ***???294±63 ***???295±66 ***??185±42 *????200±48 **???222±53 ***???214±48 ** |
With comparison before the administration,
*P＜0.05,
*P＜0.01,
* *P＜0.001
Table 7 pharmaceutical composition of the present invention to rat at the influence of the maximum fall off rate of body running heart left chamber (kPa/s) (X ± SD)
| Behind the preceding heart failure of group heart failure | After the administration (minute) |
| ??5?????????????10????????????*20????????????30 | |
| Negative control group-254 ± 61 ***-117 ± 27 experimental group-278 ± 50 ***-140 ± 31 positive drug groups-246 ± 43 ***???-132±23 | ??-118±29??????-116±27??????-115±26???????-115±29 ??-184±40 *????-201±52 **???-218±60 **????-216±68 **??-170±28 **???-183±34 **???-190±32 ***???-184±35 ** |
With comparison before the administration,
*P＜0.05,
*P＜0.01,
* *P＜0.001
Table 8 pharmaceutical composition of the present invention to rat at the influence of body running heart left chamber systolic pressure (kPa) (X ± SD)
| Behind the preceding heart failure of group heart failure | After the administration (minute) |
| ??5?????????????10?????????????20??????????????30 | |
| Negative control group 19.3 ± 2.1 ***14.0 ± 1.6 experimental group 18.6 ± 1.4 ***10.8 ± 1.0 positive drug groups 18.0 ± 1.6 ***???10.5±1.2 | ??14.2±1.1?????13.9±1.4??????14.4±1.5???????14.1±1.4 ??12.9±2.3 *???13.8±2.4 **???14.5±1.8 ***???14.1±1.9 ***??12.1±1.4 *???12.9±1.6 **???12.8±1.6 **????12.9±1.6 ** |
With comparison before the administration,
*P＜0.05,
*P＜0.01,
* *P＜0.001
Table 9. pharmaceutical composition of the present invention is pressed the influence (X ± SD) of (kPa) to rat at the body running heart left chamber end of relaxing
| Behind the preceding heart failure of group heart failure | After the administration (minute) |
| ??5??????????????10?????????????20?????????????30 | |
| Negative control group 1.04 ± 0.24 ***1.33 ± 0.19 experimental group 1.07 ± 0.20 **1.46 ± 0.24 positive drug group 1.02 ± 0.19 **?????1.31±0.19 | ??1.37±0.22?????1.36±0.22?????1.36±0.19?????1.38±0.21 ??1.36±0.24?????1.31±0.19?????1.28±0.17 *???1.32±0.18 ??1.23±0.19?????1.14±0.18 *???1.16±0.21?????1.20±0.19 |
With comparison before the administration,
*P＜0.05,
*P＜0.01,
* *P＜0.001
Table 10. pharmaceutical composition of the present invention to rat at the influence of body running heart heart rate (bpm) (X ± SD)
| Behind the preceding heart failure of group heart failure | After the administration (minute) |
| ??5??????????10?????????20?????????30 | |
| Control group 372 ± 29 ***285 ± 42 experimental group 410 ± 44 **347 ± 41 positive drug groups 373 ± 47 **????298±49 | ??285±39????282±37????280±39????281±36 ??347±52????355±50????353±57????352±63 ??301±41????297±36????302±29????300±32 |
With compare before the administration,
*P＜0.05,
*P＜0.01,
* *P＜0.001
From the result shown in the table 4-10 as can be seen, after the intravenous injection vetanarcol caused heart failure, the rat heart function obviously descended.Behind the intravenous injection physiological saline, every cardiac functional parameter of animal model for heart failure does not have obvious change, and behind intravenous injection pharmaceutical composition of the present invention and the positive control medicine Deslanoside (Wuxi City the 7th pharmaceutical factory), then every cardiac functional parameter of animal all be improved significantly.Wherein+dp/dt
MaxRise to 295kPa/s (rate of rise is 80.9%, P＜0.001) and 222kPa/s (rate of rise is 54.2%, P＜0.001) from treating preceding 163kPa/s and 144kPa/s respectively.-dp/dtmax respectively before treat-140kPa/s and-130kPa/s drops to-218kPa/s (rate of descent is 55.7%, P＜0.001) and-190kPa/s (rate of descent is 43.9%, P＜0.001).From these results as can be seen, the pharmaceutical composition that is the primary activity composition with the wooden leaf total saponins of east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion of the present invention can make the every heart function parameter of laboratory animal be able to obvious improvement really, and its effect can be compared with known cardiac glycoside medicine Deslanoside.Therefore, pharmaceutical composition of the present invention is probably as a kind of candidate's cardiac drug, is used for the treatment of the heart failure that a variety of causes causes.
Embodiment 5: east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion wood total saponin from leaves is to the provide protection of the Acute Myocardial Infarction dog heart
It is the influence of the pharmaceutical composition of primary activity composition to experimental myocardial infarction dog electrocardiogram(ECG, serum CPK and lipid peroxide (LPO) level and myocardial infarction area with east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion wood total saponin from leaves that present embodiment illustrates as the present invention.
With body weight is 18 of 11 to 15kg healthy hybrid dogs.Be divided into three groups at random.Every group each 6.In the experiment, under vetanarcol 30mg/kg intravenous anesthesia, open chest with left side the 4th intercostal, ligation ramus descendens anterior arteriae coronariae sinistrae mid point, or maximum oblique angle props up root, causes the Experimental Acute Myocardial Infarction model.Ligation coronary artery administration after 30 minutes (with 1ml/ minute speed from the external jugular vein infusion): experimental group animal intravenously is accepted pharmaceutical composition of the present invention (5.6mg/kg); Positive control treated animal intravenously is accepted beta-blockers Proprasylyte (1mg/kg); Negative control treated animal intravenously is accepted isopyknic physiological saline.
All animal patterns are carried out left carotid intubate and apex intubate, before and after causing myocardial infarction front and back and administration, monitor and record myocardiac mechanics and hemodynamic parameter, while is at the ischemic region of left ventricle, the marginarium, normal district writes down the multi-lead electrocardiogram(ECG simultaneously with multipoint adsorption electrode record epicardial electrogram.These parameters comprise the maximum grade of heart rate (HR), left ventricular systolic pressure (LVSP), intraventricular pressure (± dp/dtmax), the end of relaxing, left chamber presses (LVEDP), aortic systolic pressure (SAP), aorta flow (AF), stroke output (SV), coronary flow (CEF).
Timing acquiring blood sample and detect serum paraoxonase acid kinase (CPK) (IU/L) with ordinary method simultaneously, and lipid peroxide (LPO) is concentration (ug/ml).And calculate the summation (∑ ST) that epicardial electrogram ST section is raised, with raise 〉=number that leads of 2mv accounts for the per-cents (NST) of total number of electrodes.In addition, also finish the back and put to death animal, with nitro blue tetrazolium (N-BT) and dye heart tissue and measure myocardial infarction area (MIS) with weighting method in experimental record.Shown in the following tabulation of the result 11-13.
Table 11 Aralia manshrica total saponin from leaves composition is to the influence of dog serum CPK and LPO content
| Group (n=6) | Serum CPK (IU/1) | Serum LPO (μ g/ml) | ||
| Before the infraction | Blocked back 6 hours | Before the infraction | Block after 6 hours | |
| Negative control group positive controls experimental group | ?1170.3±53.0 ?1209.3±59.0 ?1198.0±33.0 | 2887.9±297.5 ***1626.4±246.2 **1301.3±54.7 *** | 30.9±8.7 30.7±3.6 31.0±3.2 | 38.5±9.8 **35.5±6.5 33.5±1.2 |
* compare with negative control group,
*P＜0.05,
*P＜0.01, * * * P＜0.001.
Table 12 Aralia manshrica total saponin from leaves blocks the influence of back 6 hours front multi-lead ECG to dog
| Group (n=6) | ????∑ST | ????NST | ????NQ | ????∑Q |
| Negative control group positive controls experimental group | ????35.0 ????7.9 *????8.0 * | ????123.1 ????38.78 ????36 * | ????98.70 *????74.73 *????70.69 | ????47.9 ????30.9 *????22.2 * |
*P＜0.05。
Table 13 Aralia manshrica leaf saponin to the influence of myocardial infarction dog myocardial infarction area (x+SD, n=6)
| Group | Infraction/(%) whole-heartedly | Infraction/left the heart (%) |
| Negative control group | ????21.92±2.132 | ????15.69±1.349 |
| Positive controls | ????17.08±1.489 ** | ????12.33±1.421 ** |
| Experimental group | ????16.59±1.565 ** | ????12.45±2.161 * |
Compare with the physiological saline control group,
*P＜0.05,
*P＜0.01
* *P＜0.001;
Change percentage and salt solution group relatively,
*P＜0.05
*P＜0.01
* *P＜0.001.
When the myocardial ischemia anoxic, the endochylema membrane permeability increases, and causes intracellular enzyme to be released into blood flow and thereby makes the active and LPO content increase of serum CPK.From the result shown in the table 11 as can be seen, the ligation coronary vasodilator causes the serum CPK gross activity of the ischemic control treated animal of myocardial ischemic injury to be significantly higher than blank group (P＜0.05).Oral administration can make the active increase of serum CPK be subjected to remarkable inhibition after with beta-blockers Proprasylyte or east area of the Liao River, coextensive with eastern and southern Liaoning Province green onion wood total saponin from leaves composition; and inhibition shows that as the myocardium LPO level of myocardial ischemic injury indication the east area of the Liao River, coextensive with eastern and southern Liaoning Province of the present invention green onion wood total saponin from leaves composition has almost completely identical defencive function with the general bitter edible plant Luo Er of known anti-myocardial damage medicine.
Table 12 has shown that animal cardiac muscle blocks the detected result of back 6 hours front multi-lead electrocardiogram(ECG correlation detection parameters.As the rough quantitative target of monitoring myocardial infarction generation with its severity, evaluation infarct size size, NST among the multi-lead ECG of front is the reflecting myocardium infarct size roughly, ∑ ST is reflecting myocardium infraction degree roughly, ∑ Q is the reflecting myocardium degree of necrosis roughly, and NQ reflects roughly that then the left ventricle contractility reduces degree.From the data shown in the table 12 as can be seen, the Aralia manshrica total saponin from leaves composition that comes into operation in the myocardial infarction posterior vein can reduce front multi-lead ECG ischemic change (P＜0.05) significantly.
The N-BT coloration result of cardiac muscular tissue's sample shows that the Aralia manshrica total saponin from leaves composition that comes into operation can reduce myocardial infarction area (referring to table 13) significantly substantially, and this result directly perceived conforms to fully with the ECG detected result.
Claims (7)
1, comprise and be selected from Liao Dong Aralia wood saponin(e V, VII, X Aralia wood leaf saponin A (1) Aralia wood leaf saponin(e B (2), melanthigenin-3-O-β-D-Glucopyranose-(1 → 3)-β-D-galactopyranose glucoside, melanthigenin-3-O-β-D-Glucopyranose-(1 → 3)-α-l-arabopyranose-28-O-β-D-glucopyranosyl ester glucoside, Oleanolic Acid-3-O-β-D-Glucopyranose-28-O-β-D-glucopyranosyl ester glucoside, Quercetin-3-O-β-l-pyrans rhamnoside, Oleanolic Acid-3-O-β-D-galactopyranose-28-O-β-D-glucopyranosyl ester glucoside, the distant eastern Aralia wood total saponin extracts of at least ten one kinds of monomer components of Oleanolic Acid-3-O-β-D-Glucopyranose (1 → 3)-β-D-glucopyanoside.
2, according to the extract of claim 1, wherein said Liao Dong Aralia wood total saponins is to extract in the leaf by Liao Dong Aralia wood plant to obtain.
3, the method for the distant eastern Aralia wood leaf total saponin extracts of production claim 1 is characterised in that comprising the use macroporous adsorbent resin and separates, and uses the eastern Aralia wood of Zeo-karb and decolorizing resin purifying the Liao Dynasty leaf total saponins.
4, be the primary activity composition with Liao Dong Aralia wood total saponin extracts, and contain the pharmaceutical composition of one or more pharmaceutically acceptable carriers or vehicle.
5, according to the pharmaceutical composition of claim 3, wherein comprise being selected from Liao Dong Aralia wood saponin(e V as the wooden leaf total saponins of the Liao Dong Aralia of primary activity composition, VII, X Aralia wood leaf saponin A (1) Aralia wood leaf saponin(e B (2), melanthigenin-3-O-β-D-Glucopyranose-(1 → 3)-β-D-galactopyranose glucoside, melanthigenin-3-O-β-D-Glucopyranose-(1 → 3)-α-l-arabopyranose-28-O-β-D-glucopyranosyl ester glucoside, Oleanolic Acid-3-O-β-D-Glucopyranose-28-O-β-D-glucopyranosyl ester glucoside, Quercetin-3-O-β-l-pyrans rhamnoside, Oleanolic Acid-3-O-β-D-galactopyranose-28-O-β-D-glucopyranosyl ester glucoside, at least ten one kinds of monomer components of Oleanolic Acid-3-O-β-D-Glucopyranose (1 → 3)-β-D-glucopyanoside.
6,, can contain in addition also wherein that one or more are natural or chemosynthesis, with primary activity composition Liao Dong Aralia wood leaf total saponins auxiliary or synergistic other activeconstituentss are arranged according to the pharmaceutical composition of claim 3.
7, be used for preventing and treat the application of the related pathologies conditioned disjunction disease of heart failure and myocardial ischemia in production according to the Liao Dong Aralia of claim 1 or 2 wood total saponin extracts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2003101099374A CN1552723A (en) | 2003-10-24 | 2003-10-24 | Liaodong oak leaf saponin and its medicinal composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2003101099374A CN1552723A (en) | 2003-10-24 | 2003-10-24 | Liaodong oak leaf saponin and its medicinal composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1552723A true CN1552723A (en) | 2004-12-08 |
Family
ID=34335441
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2003101099374A Pending CN1552723A (en) | 2003-10-24 | 2003-10-24 | Liaodong oak leaf saponin and its medicinal composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1552723A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1311804C (en) * | 2004-12-20 | 2007-04-25 | 史敬辉 | Bathing by using peony and preparation method |
| CN103781466A (en) * | 2011-09-08 | 2014-05-07 | 罗蒂株式会社 | Oral composition |
| KR20170063122A (en) * | 2015-11-30 | 2017-06-08 | (주)아모레퍼시픽 | Skin external composition containing aralosides |
| CN113181226A (en) * | 2021-05-14 | 2021-07-30 | 王知斌 | Aralia elata seem extract for protecting liver and preventing liver cancer, preparation method, separation detection method, composition and application |
-
2003
- 2003-10-24 CN CNA2003101099374A patent/CN1552723A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1311804C (en) * | 2004-12-20 | 2007-04-25 | 史敬辉 | Bathing by using peony and preparation method |
| CN103781466A (en) * | 2011-09-08 | 2014-05-07 | 罗蒂株式会社 | Oral composition |
| US10201493B2 (en) | 2011-09-08 | 2019-02-12 | Lotte Co., Ltd. | Method of reducing oral biofilm |
| KR20170063122A (en) * | 2015-11-30 | 2017-06-08 | (주)아모레퍼시픽 | Skin external composition containing aralosides |
| CN108366951A (en) * | 2015-11-30 | 2018-08-03 | 株式会社爱茉莉太平洋 | Composition for preparation for external use on skin containing the wooden saponin(e |
| US11052098B2 (en) | 2015-11-30 | 2021-07-06 | Amorepacific Corporation | Composition containing araloside for external application to skin |
| CN108366951B (en) * | 2015-11-30 | 2021-10-01 | 株式会社爱茉莉太平洋 | Skin external preparation composition containing wood saponin |
| KR102496013B1 (en) | 2015-11-30 | 2023-02-06 | (주)아모레퍼시픽 | Skin external composition containing aralosides |
| CN113181226A (en) * | 2021-05-14 | 2021-07-30 | 王知斌 | Aralia elata seem extract for protecting liver and preventing liver cancer, preparation method, separation detection method, composition and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101926853B (en) | Medicine composition with function of lowering blood sugar level as well as preparation method and application thereof | |
| CN101033245B (en) | Preparation method and application of pedunculoside | |
| CN1931236B (en) | Medicine composition of red sage and rhodiola root | |
| AU734851B2 (en) | The extract of pine needle and the use thereof | |
| CN103006769B (en) | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and preparation method thereof | |
| CN1923241B (en) | Medicine composition containing epimedium extract, uncaria extract, and gastrodine, and its preparation and use | |
| CN1112198C (en) | Thrombolytic medicine and its preparation and use | |
| CN1552723A (en) | Liaodong oak leaf saponin and its medicinal composition | |
| CN1206236C (en) | Manyprickle acanthopanax general saponin extractive and its medicinal composition | |
| CN1297279C (en) | Medicinal composition containing danshensu, total ara-saponin and camphol and its preparation and use | |
| CN1068790C (en) | Medicinal composition containing total saponin extracted from stem and leaves of American ginseng | |
| CN1188406C (en) | Cattail pollen extract and preparation process and use thereof | |
| CN1895540A (en) | Medicinal composition for treating cardiovascular disease, its making method and use | |
| CN101028437A (en) | Chinese-medicinal effective part composition for preventing cardiovascular disease and its production | |
| CN101623437A (en) | Pulse activating preparation for injection and its preparation method | |
| CN1899509A (en) | Chinese medicine injection for supplementing qi and recovering pulse and its preparing method | |
| CN100352480C (en) | Pharmaceutical composition, its preparation method and usage | |
| CN1698717A (en) | Chinese medicinal compound fat emulsion injection and its preparation method | |
| CN1239164C (en) | Haw effective part and its extracting method and uses | |
| CN1297278C (en) | Medicinal composition containing salvianolic acid B, total ara-saponin and camphol and its preparation and use | |
| CN1689593A (en) | Method for preparing ginseng and aconite powdered injection | |
| CN1259934C (en) | Haw leaf injection for treating cardiovascular disease | |
| CN1093416C (en) | Plant Medicine for treating cardiovascular medicine and its preparing process | |
| CN1899352A (en) | Chinese medicine effective part composition for supplementing qi and recovering pulse | |
| CN100531740C (en) | Health care products for auxiliary treatment of diseases of cardio-cerebral blood vessels |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |