CN1468860A - Manyprickle acanthopanax general saponin extractive and its medicinal composition - Google Patents
Manyprickle acanthopanax general saponin extractive and its medicinal composition Download PDFInfo
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- CN1468860A CN1468860A CNA021255369A CN02125536A CN1468860A CN 1468860 A CN1468860 A CN 1468860A CN A021255369 A CNA021255369 A CN A021255369A CN 02125536 A CN02125536 A CN 02125536A CN 1468860 A CN1468860 A CN 1468860A
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- acanthopanacis senticosi
- caulis acanthopanacis
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Abstract
The present invention relates to general saponin extractive of natural plant and is especially general saponin extractive of manyprickle acanthopanax root and its preparation process and medicinal composition as well as the application of the medicinal composition in preparing medicine for preventing and treating cardiac and cerebral vascular diseases.
Description
The present invention generally relates to the natural phant total saponin extracts, particularly relate to natural medicinal plant Folium Acanthopanacis Senticosi total saponin extracts, its preparation method, contain the pharmaceutical composition of said total saponin extracts, and said pharmaceutical composition is used in the medicine of treatment/prevention cardiac and cerebral vascular diseases and production for treating/prevention cardiac and cerebral vascular diseases.
Radix Et Caulis Acanthopanacis Senticosi (Acanthopanax senticosus (Rupr.et Maxim.) Harms) is the root and the rhizome of Araliaceae Panax medicinal plant Radix Et Caulis Acanthopanacis Senticosi, mainly be distributed in the northeast and the North China of China, next is Muscovite the Far East Area, and the Korea peninsula and Japan.In Zhong Guo the traditional medicine, people find that very early Radix Et Caulis Acanthopanacis Senticosi is a kind of valuable natural drug with " invigorating the spleen and replenishing QI, hard muscles and bones, Qiang Zhiyi " in ancient times.Along with modern chemistry, physiology and pharmacology application and the progress in the traditional Chinese medicine and pharmacy field, nearly three during the last ten years, and people have carried out comparatively deep research to the chemical structure of Radix Et Caulis Acanthopanacis Senticosi.Have now found that the main chemical compositions of Radix Et Caulis Acanthopanacis Senticosi is a triterpenoid saponin, particularly oleanolic acid saponin.For example, Suprunov (Suprunov, NI:Chemical Abstract 73:127741e, 1970) at first separates from Folium Acanthopanacis Senticosi and has obtained six kinds of monomer saponins, and is accredited as oleanolic acid saponin A, B, C, D, E and F respectively.Continue after, people such as Frolova (Frolova, GM.et al., Chemical Abstract 76:70053n, 1972; Frolova, GM.et al., Chemical Abstract 76:59965r, 1972) further separation has obtained four kinds of monomers such as olea saponin I, K, L and M again.On the basis of these researchs, (Shao, C.J.et al. such as Shao Chunjie, Chem.Pham.Bull., 36 (2): 601,1988) from Folium Acanthopanacis Senticosi, separate first and obtain 13 kinds of new triterpenoid saponins, and called after Radix Et Caulis Acanthopanacis Senticosi saponin(e (Ciwujianoside) A respectively
1, A
2, A
3, A
4, B, C
1, C
2, C
3, C
4, D
1, D
2, D
3And E.People such as Shao Chunjie studies confirm that, the aglucon of these triterpenoid saponins (glucoside unit) all belongs to the oleanane type compound, comprising oleanolic acid saponin unit, hydroxyl first oleanolic acid saponin unit with go to first oleanolic acid saponin unit.Glycosyl comprises glucose, rhamnosyl and pectinose, and is connected to the C of aglucon respectively by glycosidic link and ester glycosidic bond
3Hydroxyl and C
28On the carboxyl.In addition, the author also obtains three kinds of known saponin(es from same raw material: the Seponin-1 of Hederasaponin B, Eleutheroside K and trace.
Physiology, pharmacology and clinical pharmacology research confirm that further Radix Et Caulis Acanthopanacis Senticosi is a kind of strong class medicine that typically consolidates really, has and strengthens the body resistance to consolidate the constitution significantly and tranquilizing effect.Modern physiology and pharmaceutical research show, Radix Et Caulis Acanthopanacis Senticosi extract has outstanding biologic activity to circulation and cardio-cerebrovascular, mainly show as (1) and improve the hypoxia-bearing capability of animal and anti-adaptability to changes (referring to Wu Bingchun etc., Chinese patent medicine research, supplementary issue (2), 1984 and Golotin, V.G., et al., Chemical Abstract 110:128610f, 1989); (2) increase to exsomatize animal coronary flow (referring to Tian Baojie etc., CHINA JOURNAL OF CHINESE MATERIA MEDICA, 14 (8): 493,1989 and Ma Lina etc., Chinese Pharmaceutical Journal, 29 (11): 654,1994); And (3) reduce (little) platelet aggregation and blood viscosity (referring to Yang Qiusheng etc., Capital Medical College's journal, 12 (3): 171,1991 and Liu Yulan etc., Shenyang Pharmacy College's journal, 6 (1): 57,1989).So far, existing many about using Radix Acanthopanacis Senticosi root to be raw material, make the report (referring to Chinese patent 92109660.7,93100533.7,94109342.5,9612145.6,99126793.1 and 00108022.9) of blanket clinically nourishing drink and auxiliary therapeutical agent separately or cooperate other natural medicinal ingredients.The major defect of these prior aries is: (1) large-scale development and utilize Radix Acanthopanacis Senticosi root will cause the havoc of natural resources; (2) only utilize simple water extract will be unfavorable for in-depth analysis and research to efficient part or composition.
As the closely-related prior art of the present invention, to disclose for No. 94107718.7 with Radix Acanthopanacis Senticosi root, stem or leaf be raw material to the patent of awarding of Song Shiyue, and preparation is suitable for the method for the water and the alcohol extract of intravenous administration.This method comprises with behind the spissated aqueous extract of extraction using alcohol of final concentration 75%, re-uses the macroporous resin decolouring.As seen, the method that this patent is described is the simplest ordinary method just, and the purity of product (mainly being flavonoid compound) is difficult to guarantee.
An object of the present invention is to provide the method for producing manyprickle acanthopanax general saponin extractive, this method comprises at first makes milk of lime with CaO with the water decoction of Radix Et Caulis Acanthopanacis Senticosi; Under condition of neutral pH, make said milk of lime by macroporous adsorptive resins absorption and use ethanol elution then; Make resulting eluate by weak-type ion exchange resin and carry out routine decolouring at last again.
This purpose preferred embodiment according to the present invention, wherein the pH of said milk of lime is about 10-12.
This purpose preferred embodiment according to the present invention, leaf and/or stem that wherein said Radix Et Caulis Acanthopanacis Senticosi is the Radix Et Caulis Acanthopanacis Senticosi plant.
Another preferred embodiment of this purpose according to the present invention, wherein said Radix Et Caulis Acanthopanacis Senticosi is the leaf of Radix Et Caulis Acanthopanacis Senticosi plant.
Another preferred embodiment of this purpose according to the present invention, the alcohol concn that wherein is used for wash-out is about 70-95% (V/V).
Another preferred embodiment of this purpose according to the present invention, wherein said conventional decoloring method comprise uses decolouring of weak base type resin anion(R.A) and/or activated carbon decolorizing.
Another preferred embodiment of this purpose according to the present invention, wherein the productive rate of said manyprickle acanthopanax general saponin extractive is 1-3% (W/W).
Another object of the present invention provides by the method that is defined as above and prepares manyprickle acanthopanax general saponin extractive.
This purpose preferred embodiment according to the present invention, wherein the purity of said manyprickle acanthopanax general saponin extractive is more than 80% (W/W).
A further object of the present invention provides the pharmaceutical composition that contains the manyprickle acanthopanax general saponin extractive that is defined as above, wherein said pharmaceutical composition also contains one or more pharmaceutically acceptable carrier or vehicle except that the manyprickle acanthopanax general saponin extractive that contains as the treatment significant quantity of primary activity composition.
This purpose preferred embodiment according to the present invention, wherein said pharmaceutical composition is made into to be suitable for the various formulations of gi tract administration.
Another preferred embodiment of this purpose according to the present invention, wherein said pharmaceutical composition are made into to be suitable for the various formulations of the outer administration of gi tract.
Another preferred embodiment of this purpose according to the present invention, wherein said pharmaceutical composition is except that the extraction of acanthopanax senticousus saponins that contains as the primary activity composition, also can contain one or more have identical, similar or different biological active, and have auxiliary with said primary activity composition or synergy but not natural or synthetic other drug composition or its mixture of antagonism mutually.
The present invention generally relates to the natural phant total saponin extracts, particularly relate to natural medicinal plant Folium Acanthopanacis Senticosi total saponin extracts, its preparation method, contain the pharmaceutical composition of said total saponin extracts, and said pharmaceutical composition is used in the medicine of treatment/prevention cardiac and cerebral vascular diseases and production for treating/prevention cardiac and cerebral vascular diseases.
An object of the present invention is to provide the method for producing manyprickle acanthopanax general saponin extractive, this method comprises: the water decoction of Radix Et Caulis Acanthopanacis Senticosi is adsorbed by macroporous adsorptive resins, and use ethanol elution; And then make eluate pass through weak-type ion exchange resin, and carry out the routine decolouring.
This purpose preferred embodiment according to the present invention wherein is transferred to about 10-12 with milk of lime with the pH of said water extract filtrate.
This purpose preferred embodiment according to the present invention, leaf or stem that wherein said Radix Et Caulis Acanthopanacis Senticosi is the Radix Et Caulis Acanthopanacis Senticosi plant.
This purpose preferred embodiment according to the present invention, wherein said Radix Et Caulis Acanthopanacis Senticosi is the leaf of Radix Et Caulis Acanthopanacis Senticosi plant.
This purpose preferred embodiment according to the present invention, the alcohol concn that wherein is used for wash-out is about 70-95% (V/V).
This purpose preferred embodiment according to the present invention, wherein said conventional decoloring method comprise uses decolouring of weak base type resin anion(R.A) and/or activated carbon decolorizing.
As everyone knows, Radix Et Caulis Acanthopanacis Senticosi is a known pharmaceutically acceptable plant during Chinese traditional medicine is learned, and in the 1977 annual income Pharmacopoeias of the People's Republic of China.The root of known Radix Et Caulis Acanthopanacis Senticosi plant mainly contains eleutheroside A-E, acid or ester compound and seldom measures Radix Et Caulis Acanthopanacis Senticosi polysaccharide; The stem skin mainly contains Eugenol-β-glucose or galactoside compounds such as D-glucoside; Leaf then mainly contains Radix Et Caulis Acanthopanacis Senticosi glucoside I-M, and aforesaid 13 kinds of Folium Acanthopanacis Senticosi glycosides.Therefore, when the different anatomic position of select using the Radix Et Caulis Acanthopanacis Senticosi plant or tissue as raw material during with preparation biologic activity component or monomer component, even make same method, also may obtain composition and/or diverse compound of ratio or component because of employed raw material is different.Certainly, employed extracting method difference is for example used different reagent and/or step, also will obtain different active constituent (i.e. so-called " reactive site ") or composition.
Generally come, with respect to Radix Acanthopanacis Senticosi root, all contain the saponins compound of higher proportion in Folium Acanthopanacis Senticosi and the stem, for example total saponin content (dry weight) is 0.6-0.9% (w/w) in the Radix Acanthopanacis Senticosi root.And total saponin content (dry weight) even can be in the cauline leaf up to 1.5% (W/W) (Chemical Abstract, 72:19118r, 1970).Therefore, be purpose of the present invention, our preferred raw material is Folium Acanthopanacis Senticosi and stem, and particularly preferred raw material is a Folium Acanthopanacis Senticosi.
Briefly,, at first be equipped with through the excessive water of adding volume in the container of pretreated Folium Acanthopanacis Senticosi in order to obtain required Radix Et Caulis Acanthopanacis Senticosi total saponins, and heated and boiled 1-4 hour.In order to increase the yield of water extract as much as possible, can prepare the method for Chinese herbal medicine decoction according to routine, under the heated and boiled condition, the raw material crude drug is extracted 2-4 time repeatedly with excessive water.Collect and filter the water extract that so obtains then.
Stir down and make milk of lime, gained filtrate (water extract) is made the about 10-12 of pH with unslaked lime (CaO) so that wherein the flavones that is contained and tannin to precipitate with solids bonded mode.After filtering once more, transfer to neutrality with the sour pH that will mainly contain the filtrate of saponin constituent and glucide, be beneficial to continue after the saponin(e in the filtrate is adsorbed on the macroporous adsorptive resins.Wash post then with water to remove the impurity that contains in the filtrate based on saccharide compound.Be washed to colourless after, just can use general concentration to be 70-95%, better concentration be the ethanol elution adsorption column bonded of 80-90% (v/v), based on the combined thing of saponin(e.The flow velocity of coupled columns wash-out is not specifically limited, and generally keeps the natural flow velocity of elutriant to get final product.
After collecting elutant, for example can make it at first to pass through the pre-treatment of weak-type cation exchange resin column, and then use for example weak base type anion-exchange resin column decolouring.The product that decolouring is handled through resin column may still have light yellow color, in order further to improve degree of purity of production and outward appearance, can reuse activated carbon treatment in case of necessity, so that further decolour by the eluate of decolorizing resin.Through behind the activated carbon decolorizing,, also may cause the reduction of product yield sometimes though can make degree of purity of production bring up to 95%.In general, calculate by dry weight, the productive rate of the Radix Et Caulis Acanthopanacis Senticosi total saponins that makes according to the inventive method is about 1-3%.Simultaneously, use olea saponin(e B as standard substance, the product purity that records with colorimetry or spectrophotometry is that about 85% (only resin decolorization) is to about 95% (w/w) (resin decolorization adds activated carbon decolorizing).
Another object of the present invention provides the manyprickle acanthopanax general saponin extractive, particularly Folium Acanthopanacis Senticosi total saponin extracts of preparation as stated above.
This purpose preferred embodiment according to the present invention, wherein the purity of said manyprickle acanthopanax general saponin extractive is more than 80%, and is passing through secondary (gac) decolouring its purity of back even can reach about 95% (w/w) or higher.
In addition, press the dry weight of Radix Et Caulis Acanthopanacis Senticosi raw material and calculate, be about 1-3% according to the yield of manyprickle acanthopanax general saponin extractive of the present invention.
By above description and the fact as can be seen, the method of production manyprickle acanthopanax general saponin extractive of the present invention and the major advantage that is had by the Radix Et Caulis Acanthopanacis Senticosi total saponins product that this method directly obtains comprise: (1) technology is relatively simple, and does not need special or large-scale equipment; (2) employed reagent or material are relatively cheap in the method, and all nontoxic; (3) purity of resulting product is higher relatively, and has met or exceeded the standard of Chinese medicine second kind new medicine of China national drug surveilance and management board's " new drug reviewing way " regulation.
Therefore, the method for production manyprickle acanthopanax general saponin extractive of the present invention is not only a kind of ten minutes useful method, and is to be particularly suitable for the method that large-scale industrial production uses.As previously mentioned, not only technology is easy for the inventive method, the yield of product is higher, and can not cause environmental pollution basically.
A further object of the present invention provides the pharmaceutical composition that contains the manyprickle acanthopanax general saponin extractive that is defined as above, wherein said pharmaceutical composition also contains one or more pharmaceutically acceptable carrier or vehicle except that the manyprickle acanthopanax general saponin extractive that contains as the treatment significant quantity of primary activity composition.
As the primary activity composition of pharmaceutical composition of the present invention, the relevant composition of Radix Et Caulis Acanthopanacis Senticosi total saponins with it, to central nervous system, immunity system, cardiovascular systems and E﹠M system all show biologic activity in various degree.But as previously mentioned, wherein making us interested especially is Radix Et Caulis Acanthopanacis Senticosi total saponins to the unify influence of platelet aggregation of cardiovascular system.
We utilize various animal model, and the pharmacodynamics of manyprickle acanthopanax general saponin extractive of the present invention has been carried out extensive studies (referring to embodiment 3-7).The result of these researchs comprises:
1. for dog and rat acute myocardial infarction model, manyprickle acanthopanax general saponin extractive of the present invention (15,30mg/kg) can alleviate myocardial ischemia (or myocardial infarction) degree and the scope of laboratory animal significantly, and reduces serum aspartic acid aminotransferase (AST), creatine phosphokinase (CK) and serum lactic dehydrogenase (LDH) activity significantly; Reduce platelet adhesion reaction and aggregation; Obviously reduce that whole blood is lowly cut, height is cut viscosity and plasma viscosity.In addition, the acute myocardial ischemia model that brings out for the rat pituitary pituitrin, the manyprickle acanthopanax general saponin extractive of the present invention of various dose (25,50,100mg/kg) can alleviate the ischemia ECG change significantly, and proves that thus it has anti-acute myocardial ischemia activity.
2. in acute myocardial infarction dog heart function and haemodynamics test, as seen manyprickle acanthopanax general saponin extractive of the present invention (15,30mg/kg) is reducing heart rate (HR) significantly, reduce left ventricular pressure (LVP), mean arterial pressure (MAP) and total peripheral resistance (TPR), show that this extract can alleviate the forward and backward load of heart, reduce cardiac work and myocardium keto consumption.In addition, this extract also can make ventricular diastole prolong, and increases the coronary perfusion time, thereby helps dwindling myocardial infarction area.
3. in the test of the coronary circulation of acute myocardial infarction dog and oxygen metabolism, manyprickle acanthopanax general saponin extractive of the present invention (15,30mg/kg) can increase myocardial blood flow after the infarct significantly, reduce the coronary artery vascular resistance, and both acts on the time-histories basically identical.This extract (40,80,160mg/kg) also can improve mouse cardiac muscle significantly
86The Rb uptake ratio increases the myocardial nutrition volume of blood flow.In addition, manyprickle acanthopanax general saponin extractive of the present invention (15,30mg/kg) also can reduce myocardium oxygen uptake rate, myocardial consumption of oxygen and myocardial oxygen consumption index significantly.
4. in anti-arrhythmia test, manyprickle acanthopanax general saponin extractive of the present invention (50,100mg/kg) is to BaCl
2Due to rat ventricular have tangible prevention and therapeutic action, and can improve cavy significantly to the poison dosis tolerata of ventricular premature contraction, ventricular tachycardia and the ventricular fibrillation bring out of ouabain.
5. in hyperlipemia model of rats, manyprickle acanthopanax general saponin extractive of the present invention (25,50,100mg/kg) can increase serum high-density LP cholesterol (HDL-c) significantly, reduces the ratio that serum total cholesterol reduces (TC), TC/HDL-c and LDL-c/HDL-c.
Can be according to known method in the pharmaceutical industry (referring to Remington ' s Pharmaceutical Science.15thed., Mack Publishing Company, 1980), the extract that will contain Radix Et Caulis Acanthopanacis Senticosi saponin(e and its related compound and one or more pharmaceutically acceptable carriers or vehicle or thinner mix by proper proportion, and by the pharmaceutical composition of making various different dosage forms of the present invention after the currently known methods degerming.
For example, according to the difference of route of administration, pharmaceutical composition of the present invention can be mixed be suitable in (in thoracic cavity, abdominal cavity, spinal cavity, encephalic and joint capsule) in intravenously, intramuscular, the body cavity, the tissue, the injectable solution or the dispersion agent of intracutaneous or subcutaneous administration; Or be suitable for powder agent, tablet, granule, pill, emulsion, suspension agent, capsule, the tincture of oral administration; Or be suitable for topical and sprays, creme, emulsion, ointment, gelifying agent, lozenge or suppository etc. by skin or mucosal absorption administration.
This purpose preferred embodiment according to the present invention, wherein said pharmaceutical composition can be made into to be suitable for the various formulations of the outer administration of gi tract.
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 (as 1-100mmol) 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 xitix), microbiotic (as penicillin and Streptomycin sulphate or other anti-mycotic agent) and sanitas (as Sodium Benzoate, trichloro-butyl alcohol, 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.
Another preferred embodiment of this purpose according to the present invention, wherein said pharmaceutical composition can be made into to be suitable for the various formulations of gi tract administration.
In order to prepare tablet, powder agent, capsule, granule or the emulsion that is suitable for oral administration, can use sugar 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, buffering salt, 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.
In order to prepare the preparation that is suitable for external application or topical, Radix Et Caulis Acanthopanacis Senticosi total saponins and its related compound can be dissolved in water-bearing media or other appropriate carriers or the matrix, and mix with suitable cutaneous permeable agent such as dimethyl sulfoxide (DMSO) or laurocapram, make sprays or aerosol.In addition, also can use suitable matrix or vehicle pharmaceutical composition of the present invention to be made emulsion, creme, ointment, gelifying agent or the suppository (as vaginal suppository or rectal suppository) that is suitable for the part or passes through skin or mucosal absorption administration.For this reason, can use glycerine, Magnesium Stearate, polyoxyethylene glycol, polyacrylamide, cholesterol, Yelkin TTS, methylcellulose gum or carboxymethyl cellulose, talcum powder, lactose, dextran, starch etc. as matrix or vehicle.
Difference according to application target, pharmaceutical composition of the present invention is except that the Radix Et Caulis Acanthopanacis Senticosi saponin(e and its related compound that contain as the primary activity composition, also can contain one or more have identical, similar or different biological active, and have auxiliary or synergistic natural or synthetic other drug composition or its mixture with the primary activity composition.
According to the present invention, that said other activeconstituents comprises natural origin or synthetic cardiovascular and cerebrovascular expander, antineoplastic agent, antiseptic-germicide or antiviral agent, tranquilizer, antioxidant, thrombogenesis inhibitor, and immunomodulator etc.
In general, the oral administration dosage of pharmaceutical composition of the present invention was generally 0.1-100mg/kg/ days, was preferably 1-80mg/kg/ days, was preferably 5-50mg/kg/ days; Intraperitoneal or intramuscular injection dosage were generally 0.05-100mg/kg/ days, were preferably 0.1-80m/kg/ days, were preferably 0.5-50mg/kg/ days; The intravenous injection dosage was generally 0.01-100mg/kg/ days, was preferably 0.05-80mg/kg/ days, was preferably 0.1-50mg/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.
In view of the above-mentioned known pharmacological activity of the manyprickle acanthopanax general saponin extractive for preparing by the inventive method, therefore might use disease or pathological states such as medicine composite for curing of the present invention or prevention cental system excitement/inhibit feature imbalance, maincenter or tissue ischemia/anoxic, coronary artery blood vessel blood supply insufficiency, cardiac insufficiency, thrombosis.In addition, also can use the auxiliary therapeutical agent of pharmaceutical composition of the present invention as antineoplastic agent, anti-inflammatory agent, lipid regulating agent etc.
The following example is intended to further illustrate, rather than restriction the present invention.What should spell out is, under the prerequisite of the present invention's spirit and principle, any change that the indivedual inessential technical characterictic of the present invention is done and change all will fall into the present invention and await the reply in the scope of claim.Embodiment 1: the preparation of Folium Acanthopanacis Senticosi total saponin extracts
Take by weighing about 1000 grams of the exsiccant Folium Acanthopanacis Senticosi of collecting season midautumn, clean and smash to pieces the back to the water that wherein adds about 13 times of volumes.Soaking 2 hours post-heating boiled about 2 hours.So, decoct repeatedly 4 times change liquid (immersion water) and boil under the condition of after-filtration at every turn.Simultaneously, the filtrate after collection and merging are boiled at every turn.Stir the milk of lime that slowly adding unslaked lime is made in gained filtrate down, pH is adjusted to about 11.After filtrate placed 2 hours, filter once more and use about HCl (1mol/L) that the pH of this filtrate is transferred to about 7.0.
Then gained filtrate is gone up the D101 macroporous adsorptive resins.Fully after the absorption, wash post with deionized water earlier, till effluent liquid does not have macroscopic color.Use the ethanol elution of about 80% (V/V) then, and till the saponin(e reaction that is washed till effluent liquid is negative.Collect eluate (liquid) and cross 732 type weakly acidic cation-exchange resin posts.Collect effluent liquid then and cross D941 type weak base anion-exchange resin post once more.At last, collect resulting effluent liquid, concentrating under reduced pressure and evaporation drying, obtain about 24.3 the gram white powder the Folium Acanthopanacis Senticosi total saponin extracts.Embodiment 2: the preparation of solution state Folium Acanthopanacis Senticosi total saponin extracts
Take by weighing exsiccant Folium Acanthopanacis Senticosi 100kg, put in the extractor, boiling three times.Three times decocting time was followed successively by 2.5,2.0,1.5 hours, and amount of water is followed successively by 10,8,6 times of medicinal material weight.After decoction is finished, merge decoction liquor and conventional filtration.Filtrate is slowly injected pretreated 200kg AB8 type macroporous adsorptive resins through header tank, and wash with water to effluent liquid almost colourless, and then with 85% (v/v) ethanol elution.Be collected into colourless elutriant and move in the concentrating under reduced pressure jar.Decompression recycling ethanol, and eluate is concentrated into flowing soaking paste, make its relative density reach 1.15 (20 ℃).Under agitation, left standstill 24 hours so that the extractives precipitation is separated out to 95% ethanol that wherein adds 4 times of amounts.When recovery ethanol to relative density reached 1.05～1.10 (20 ℃) after filtering, spraying drying obtained pulverous Radix Et Caulis Acanthopanacis Senticosi total saponins extractives.
Accurately take by weighing Folium Acanthopanacis Senticosi total saponins powder 25g, add water for injection 2000ml dissolving and gained solution is transferred to pH=6.5～7.5.Then, to wherein add activated carbon 6g (0.3%, w/v), and in boiling water bath, heated 10～15 minutes.Behind the conventional filtration again with filtrate with 0.02 μ filtering with microporous membrane degerming, make solution state Folium Acanthopanacis Senticosi total saponins.Embodiment 3: pharmaceutical composition of the present invention is to the influence of dog acute myocardial infarction (AMI) model
30 of the healthy adult hybrid dogs of body weight 12～15kg, be divided into 5 groups at random, every group 6: the myocardial infarction group (negative control group) of the blank group of a pump pickle, a pump pickle, injection known drug dish arteries and veins spirit (6ml/kg, 11.3 times of quite clinical daily dosage portion 20ml/60kg) positive controls and the experimental group of injecting pharmaceutical composition of the present invention (15,30mg/kg, 5.6,11.2 times of quite clinical daily dosage portion 100mg/60kg).After vetanarcol (30mg/kg) intravenous injection anesthetized animal and neck tracheostomize intubate, the 4th intercostal is opened chest in a left side, separating a blunt edge that circles round on a coronary artery left side props up, LAD the 1st, 2 branches and prop up with each side of blunt edge Zhi Xianglian and ramus anastomoticus in order to ligation, make the predetermined approximately quite left chamber of ischemic region 1/2 of the wall front surface that dissociates.With the wet cloth formula absorption method mapping epicardial electrogram (EECG) of multiple spot, get 24 mapping points and be divided into normal district, infarct marginarium and infarct central section.Postoperative was stablized 15 minutes, and record each point EECG is worth before as administration.Except that the blank saline group was only separated not ligation of coronary artery, other each group was all executed coronary ligation.After ligation, soup was dissolved in the 200ml physiological saline constant speed venoclysis 90 minutes in 5 minutes.The record EECG of administration after 30,60,90,120,180,240,300,360 minutes shows ∑-ST value with ST section total mV numerical table that raises, and is N-ST with the number that leads of ST section rising＞2mV.Got blood from femoral artery in 360 minutes after the ligation, survey serum aspartic acid aminotransferase (AST), creatine phosphokinase (CK) and serum lactic dehydrogenase (LDH) activity with the COBAS-FAARA automatic biochemistry analyzer; Calculate platelet adhesion rate with LBY-F5 platelet adhesion reaction instrument; MA when adopting the LBY-NJ2 platelet aggregation instrument to measure 3 minutes; Use LBY-N6A self-stip rotational viscosimeter measure whole blood low cut (10/s), in cut (40/s), height is cut (120/s) viscosity and plasma viscosity (120/s).It is dirty to core simultaneously, removes to take by weighing left chamber weight in wet base after atrium and right ventricle organize.Be parallel to coronary sulcus with 4～5 of left chamber crosscuts, carry out N-BT dyeing.Treat to take out immediately when the infarcted myocardium boundary line is known, cut infarcted myocardium and weigh.With the per-cent of infarcted myocardium and left chamber weight in wet base as myocardial infarction area (MIS).Shown in the following tabulation of the result 1-4.
(1) to the influence of AMI dog degree of myocardial ischemia
From tabulating the result shown in 1 down as can be seen, to animal pattern Radix Et Caulis Acanthopanacis Senticosi saponin(e extractives of the present invention (15mg/kg) the back different time (90,120,240 minutes) that comes into operation, the ∑ of animal-ST value be improved significantly, and the significant difference (p＜0.05) of comparing with negative control group.More heavy dose of medication (30mg/kg) back 60,90,120,180,240,300 minutes, ∑-ST value of visible animal pattern obviously reduces, and with negative control group group comparing difference remarkable (p＜0.05 or 0.01).
Table 1 pharmaceutical composition of the present invention is to influence (∑-ST, Mv) (x ± s, n=6) the time negative control group experimental group positive controls of AMI dog degree of myocardial ischemia
(15mg/kg) (30mg/kg) (6ml/kg) 30min 20.15 ± 0.78 19.20 ± 1.81 18.75 ± 2.37 19.26 ± 2.5860min 18.49 ± 0.91 17.50 ± 1.92 16.89 ± 1.45 behind preceding 5.80 ± 1.31 5.60 ± 2.05 5.50 ± 1.28 5.90 ± 1.47 medicines of medicine
*16.91 ± 2.1290min 16.57 ± 2.03 14.21 ± 1.30
*13.67 ± 2.30
*14.17 ± 1.28
*120min 14.60 ± 1.14 13.07 ± 1.18
*11.75 ± 1.48
*12.24 ± 2.25
*180min 14.31 ± 3.08 11.81 ± 2.60 10.61 ± 1.06
*11.11 ± 1.20
*240min 13.54 ± 1.37 10.94 ± 1.40
*10.31 ± 1.70
*10.50 ± 1.52
*300min 11.80 ± 1.76 10.82 ± 2.48 9.78 ± 1.16
*9.98 ± 0.96
*360min 11.50 ± 2.54 10.40 ± 1.52 9.56 ± 2.14 9.70 ± 1.48
Compare with negative control group,
*P＜0.05,
*P＜0.01.
(2) to the influence of AMI dog myocardial ischemia scope (N-ST)
From tabulating the result shown in 2 down as can be seen, come into operation behind Radix Et Caulis Acanthopanacis Senticosi saponin(e extractives of the present invention (15mg/kg) different time (120,180,240,300 minutes) to animal pattern, obviously reduced the degree of myocardial ischemia of animal, and with negative control group comparing difference significantly (p＜0.05).Behind the administration 30mg/kg 60,90,120,180,240,300 minutes, the myocardial ischemia scope of visible animal obviously reduced, and with negative control group comparing difference highly significant (p＜0.05 or 0.01).
Table 2 pharmaceutical composition of the present invention is to influence (N-ST, point) (x ± s, n=6) the time negative control group experimental group positive controls of AMI dog myocardial ischemia scope
(15mg/kg) (30mg/kg) (6ml/kg) 30min 110.2 ± 19.2 105.80 ± 18.6 98.75 ± 16.5 101.21 ± 15.460min 108.9 ± 16.1 96.50 ± 11.9 85.80 ± 14.5 behind preceding 15.80 ± 4.38 15.90 ± 2.85 15.50 ± 4.21 15.70 ± 3.17 medicines of medicine
*89.91 ± 12.2
*90min 99.78 ± 12.3 92.51 ± 17.3 66.82 ± 19.8
*78.67 ± 16.8
*120min 94.60 ± 17.4 72.15 ± 16.6
*58.95 ± 12.4
*64.67 ± 11.5
*180min 85.38 ± 13.8 68.21 ± 12.6
*55.98 ± 19.6
*61.61 ± 14.2
*240min 71.54 ± 16.3 52.98 ± 10.4
*44.33 ± 11.7
*50.50 ± 13.2
*300min 63.82 ± 11.6 43.85 ± 14.8
*39.78 ± 16.6
*41.98 ± 15.1
*360min 48.59 ± 14.5 38.40 ± 11.5 34.56 ± 10.4 39.70 ± 16.8
Compare with negative control group,
*P＜0.05,
*P＜0.01.
(3) to the influence of AMI dog myocardial infarction area (MIS) and three kinds of myocardium enzyme (AST, CK, LDH)
From tabulating the result shown in 3 down as can be seen: negative control group and blank group compare, and MIS and serum AST, CK, LDH activity all obviously increase (P＜0.01 or 0.001).Experimental group (15,30mg/kg) and negative control group relatively, the acute myocardial infarction area (MIS) of visible laboratory animal obviously dwindles (P＜0.01 or 0.001), and serum AST, CK and active obviously reduce (P＜0.05 or 0.01) of LDH.These results show that Radix Et Caulis Acanthopanacis Senticosi saponin(e extractives of the present invention has significant function of resisting myocardial ischemia.
Table 3 pharmaceutical composition of the present invention is to function of resisting myocardial ischemia (x ± S, n=6) group MIS (%) AST (U/L) CK (U/L) LDH (U/L) blank group-43.8 ± 12.5 579.2 ± 142.5 396.0 ± 101.5 negative control group 18.2 ± 3.5 165.5 ± 74.2 of AMI dog
##1411.0 ± 353.7
###998.6 ± 249.3
###Experimental group 15mg/kg 10.6 ± 2.5** 76.5 ± 21.2* 887.2 ± 244.8* 610.5 ± 201.4*30mg/kg 9.1 ± 2.5*** 71.9 ± 28.8* 794.6 ± 229.4** 586.5 ± 158.4** positive controls 6ml/kg 10.4 ± 2.7**, 79.2 ± 18.9*, 812.3 ± 185.0**, 582.9 ± 171.2** and blank group relatively ##P＜0.01 ###P＜0.001 and negative control group relatively * p＜0.05 * * p＜0.01 * * * p＜0.001 (four), on the impact of AMI dog Adherence of Platelet and aggregation
1. in preceding method, 360 minutes femoral artery blood sampling 1ml behind the ligation coronary vasodilator from animal pattern, with 3.8% Sodium Citrate by ratio anti-freezing in 1: 9 processing after, get in the 10ml adding 1ml thrombocyte diluent.The shake mixing splashes into cell counting count board, leaves standstill platelet Counting number under opticmicroscope 10 minutes.Residue blood adds in the LBY-F5 platelet adhesion reaction instrument ball, rotates after 15 minutes, and the platelet count after counting adheres under light microscopic, and calculate platelet adhesion rate.
The result shows, the platelet adhesion reaction of negative control group obviously improves, with blank group comparing difference significantly (P＜0.01), the experimental group animal of injecting Radix Et Caulis Acanthopanacis Senticosi saponin(e extractives of the present invention (15,30mg/kg) has then reduced platelet adhesion reaction (P＜0.05 or P＜0.01) (seeing Table 4) significantly.
2. in preceding method, 360 minutes femoral artery blood sampling 3ml from animal pattern are with 3.8% Sodium Citrate anti-freezing mixing, centrifugal 5 minutes with 180 rev/mins in 1: 9 ratio behind the ligation coronary vasodilator.Get supernatant then as platelet rich plasma (PRP), put into 0.5ml doffer pipe, put in the constant temperature hole standby.Remaining anticoagulation centrifugal 10 minutes with 300 commentaries on classics/min, with the gained supernatant as platelet poor plasma (PPP).Get each 200 μ l of PPP and PRP, the MA when adopting the LBY-NJ2 platelet aggregation instrument to measure 3 minutes.
The result shows, the platelet aggregation of negative control group obviously improves, with blank group comparing difference significantly (P＜0.05), the experimental group animal of injecting Radix Et Caulis Acanthopanacis Senticosi saponin(e extractives of the present invention (15,30mg/kg) has then reduced platelet aggregation and adhesive capacity (P＜0.05 or P＜0.01) (seeing Table 4) significantly.
Table 4 pharmaceutical composition of the present invention is to the influence of AMI dog platelet adhesion reaction and aggregation (group number of animals platelet adhesion rate (%) 3min MA (%) blank group 6 0.113 ± 0.049 59.58 ± 21.60 negative control group 6 0.226 ± 0.059 of x ± s)
##99.98 ± 28.52
#Experimental group 15mg/kg 6 0.150 ± 0.061* 66.42 ± 20.13*30mg/kg 6 0.121 ± 0.060** 60.54 ± 22.65* positive controls 6ml/kg 6 0.124 ± 0.057**, 62.78 ± 25.20* and blank group relatively #P＜0.05 ##P＜0.01 and negative control group relatively * p＜0.05 * * p＜0.01 (five), to the influence of AMI dog whole blood and plasma viscosity
In preceding method, 360 minutes femoral artery blood sampling 3ml behind the ligation coronary vasodilator from animal pattern, add 1% anticoagulant heparin, therefrom get 1ml add measure in the LBY-N6A self-stip rotational viscosimeter whole blood low cut (10/s), in cut (40/s), height is cut (120/s) viscosity, residue 2ml blood centrifugal 10 minutes with 3000 commentaries on classics/min is got upper plasma and is surveyed plasma viscosity (120/s).
The result shows, the negative control group whole blood is low to be cut, height is cut viscosity and plasma viscosity all obviously improves, and with blank group comparing difference significantly (P＜0.05 or P＜0.01), do not have obvious change but cut viscosity in the whole blood.The experimental group animal of injecting Radix Et Caulis Acanthopanacis Senticosi saponin(e extractives of the present invention (15,30mg/kg) has reduced significantly then that whole blood is lowly cut, height is cut viscosity and plasma viscosity (P＜0.05 or P＜0.01).Though centering is cut viscosity the reduction effect is arranged, compare no significant difference (P＞0.05) with negative control group.Shown in the following tabulation 5 of result.
Table 5 pharmaceutical composition of the present invention is to the influence of AMI dog whole blood and plasma viscosity (n=6, x ± s)
Whole blood viscosity group plasma viscosity
10/s 40/s 120/s (120/s) blank group 10.15 ± 2.85 6.05 ± 1.62 4.73 ± 1.25 1.50 ± 0.65 negative control group 18.75 ± 5.52
##6.95 ± 2.12 6.96 ± 2.08
#2.59 ± 0.82
#Experimental group 15mg/kg 11.82 ± 3.24* 5.57 ± 2.46 4.82 ± 1.09*, 1.62 ± 0.58*30mg/kg, 10.29 ± 3.45**, 5.12 ± 2.32 4.38 ± 1.16*, 1.28 ± 0.44** positive controls 6ml/kg, 10.85 ± 4.67*, 4.71 ± 1.60*, 4.06 ± 0.56**, 1.19 ± 0.49** and blank group relatively #P＜0.05 ##P＜0.01 compare * p＜0.05 * * pp＜0.01 embodiment 4 with negative control group: pharmaceutical composition of the present invention is on the impact of AMI dog haemodynamics and Myocardial Oxygen Metabolism
This experiment is on the basis of embodiment 3 described experiments, simultaneously animal pattern is carried out the right common carotid artery intubate, connects AP-621G carrier amplifier record arteriotony (SBP, DBP) through pressure transducer.Separate right common femoral artery, cut and insert 8
#Heart catheter connects pressure transducer and connects the AP-621G carrier amplifier to left chamber, record left indoor pressure (LVP) (the calibration sensitivity is 100mmHg/10mm).The LVP electrical signal is amplified 10 times, trace the curve base portion, the weight break point that changes rapid rising in the slow microlitre of curve into reads left chamber end-diastolic pressure (LVEDP).Simultaneously, with LVP electrical signal input differentiator, trace left indoor pressure change maximum rate (± dp/dtmax).Wherein the differentiator time constant is 1ms, High frequency filter 50Hz, and the calibration sensitivity is zero line ± 1000mmHg/s/5mm.Separate LCA and aortic root, place the magnetic flow meter probe of suitable internal diameter after, connect MF-27 type electromagnetic flowmeter determination coronary flow and aorta flow.Four limbs connect limb leads, and bioassay standard II leads electrocardiogram(ECG (ECG) and calculates heart rate (HR).With above-mentioned each index before administration and administration after 30,60,90,120,180,240,300,360 minutes synchronization timings be recorded on the RM-6000 type polygraph.Got blood simultaneously from coronary sinus vein and left femoral artery respectively in 60,120,180,240,300,360 minutes before administration and after the administration, measure blood oxygen with CORNING178 type Bloodgas Analyzer.And press document (Chun-Jie Shao, et al, Chem Pharm Bull, 1988; 36 (2): the general formula of describing 601) calculates following each parameter: mean arterial pressure (MAP), total peripheral resistance (TPR), cardiac index (CI), SI (SI), stroke work index (LVWI), myocardial blood flow (MBF), coronary vascular resistance (CVR), oxygen consumption of myocardium, myocardium oxygen uptake rate and myocardial oxygen consumption index.
The blank group is each parameter kept stable of haemodynamics in 360 minutes observation periods.Considerable change appears in each parameter of negative control group haemodynamics, and show as: HR obviously slows down, and SBP, DBP, MAP, LVP, CO, SI, CI and MBF obviously reduce, and TPR, CVR, LVWI and LVEDP obviously increase (data not shown goes out).Compare with negative control group, as seen the HR of experimental group animal of pharmaceutical composition of the present invention (15,30mg/kg) of coming into operation obviously slows down, LVP, MAP, TPR, LVWI and LVEDP reduce, show that the forward and backward load of heart alleviates, cardiac work and myocardium keto consumption reduce, and ventricular diastole prolongs, thereby has increased the infusion time of coronary artery.Pharmaceutical composition of the present invention influences shown in the following tabulation 6 the myocardium oxygen metabolism of animal pattern, myocardium oxygen uptake rate, myocardial consumption of oxygen and myocardial oxygen consumption exponential.
Table 6 pharmaceutical composition of the present invention to the influence of AMI dog cardiac muscle oxygen metabolism (x ± s, n=6)
After the administration before the group administration
60 ' 120 ' 180 ' 240 ' 300 ' myocardial consumption of oxygen (ml/100g/min) negative control group, 8.70 ± 1.7 8.40 ± 1.2 9.19 ± 1.2 9.70 ± 1.7 10.6 ± 1.3 10.2 ± 1.8 experimental group 15mg/kg 8.80 ± 1.4 7.60 ± 1.8 7.21 ± 1.8
*7.50 ± 1.4
*8.20 ± 1.8
*8.80 ± 2.030mg/kg 8.65 ± 1.3 7.40 ± 1.6 7.20 ± 1.2
*7.30 ± 1.5
*8.10 ± 1.7
*7.60 ± 1.4
*Positive controls 6ml/kg 9.04 ± 2.7 7.75 ± 1.3 7.25 ± 1.4
*7.42 ± 1.2
*8.25 ± 1.4
*8.90 ± 1.8 myocardium oxygen uptake rate (%) negative control group 54.1 ± 7.9 58.0 ± 8.7 62.1 ± 9.6 66.2 ± 8.7 76.2 ± 12.6 77.1 ± 13.6 experimental group 15mg/kg 54.8 ± 6.0 56.7 ± 6.1 47.6 ± 9.5
*51.6 ± 8.5
*62.6 ± 16.2 64.6 ± 12.530mg/kg 59.1 ± 8.6 57.2 ± 6.8 48.2 ± 8.9
*47.9 ± 9.8
*57.1 ± 9.5
*61.2 ± 7.5
*Positive controls 6ml/kg 61.1 ± 9.2 59.5 ± 8.9 49.0 ± 6.7
*52.7 ± 7.5
*59.0 ± 8.7
*60.6 ± 8.7
*Myocardial oxygen consumption index negative control group 22.9 ± 4.3 20.5 ± 3.1 18.6 ± 2.4 16.4 ± 3.6 14.8 ± 2.9 13.7 ± 3.2 experimental group 15mg/kg 23.5 ± 3.0 21.4 ± 3.0 19.8 ± 2.7 18.3 ± 4.8 16.9 ± 3.5 15.8 ± 2.230mg/kg 23.4 ± 4.6 21.0 ± 4.7 20.8 ± 5.2 19.1 ± 6.9 17.2 ± 6.2 16.0 ± 5.8 positive controls 6ml/kg 23.7 ± 5.1 21.3 ± 4.7 20.8 ± 4.7 19.9 ± 7.1 18.0 ± 3.1*16.4 ± 3.3
*
Compare with negative control group,
*P＜0.05 embodiment 5: pharmaceutical composition of the present invention is to BaCl
2The prevention of the rat ventricular that brings out and therapeutic action
100 of the Wistar rats of body weight 190～280g (male and female half and half), be divided into 5 groups at random: blank group, positive controls (verapamil 1mg/kg), and the experimental group of three injection pharmaceutical compositions of the present invention (25,50,100mg/kg), every group of 10 animals.After intravenous injection 10% Chloral Hydrate (300mg/kg) anesthesia, face upward fixedly animal and trace the II lead electrocardiogram of position.By sublingual vein injection 0.4%BaCl
2(4mg/kg) bring out irregular pulse.Prevention administration: in injection BaCl
2Preceding 3 minutes respectively through sublingual vein injection verapamil 1mg/kg and pharmaceutical composition of the present invention 25,50,100mg/kg.Control group then gives equal-volume physiological saline.Treatment administration: in injection BaCl
2Occur after the irregular pulse 1 minute respectively through sublingual vein injection verapamil 1mg/kg and pharmaceutical composition of the present invention 25,50,100mg/kg.Control group gives equal-volume physiological saline.Then, observe and write down the time that irregular pulse and irregular pulse time length and recovery sinus rhythm whether occur.
The result as seen, 10 animal sublingual veins of control group injection BaCl
2After, multifocal ventricular tachycardia appears in 0.42 ± 0.10 minute, and lasting 10-15 minute.The pharmaceutical composition of the present invention (25mg/kg-100mg/kg) of various dose can make 10 animals irregular pulse (comparing p＜0.001 with control group) not occur in 4.80 ± 2.10 minutes to 7.20 ± 2.60 minutes, shows that pharmaceutical composition of the present invention is to BaCl
2Due to rat ventricular have prophylactic effect.On the other hand, in 15 minutes that observe, 10 animals of blank group transfer hole normal cardiac rhythm (0/10) to there is no ventricular tachycardia behind the physiological saline, the pharmaceutical composition of the present invention (25mg/kg-100mg/kg) that comes into operation then can make 2-8 rat ventricular tachycardia transfer the hole normal cardiac rhythm in 1 minute, and more than the lasting 7-15min.Other has 2 rat chamber speed to alleviate.As seen 9 animal ventricular tachycardias of positive controls (verapamil 1mg/kg) transferred hole normal cardiac rhythm (9/10) to and continue more than 15 minutes in 1 minute, and wherein 1 animal housing's speed alleviates.Through four fold table X
2Check shows, pharmaceutical composition of the present invention (50,100mg/kg) and verapamil (1mg/kg) are to BaCl
2Due to rat ventricular all have therapeutic action (with control group relatively p＜0.05 or p＜0.01).Embodiment 6: pharmaceutical composition of the present invention is to the influence of hyperlipidemia rats cholesterol and lipoprotein-cholesterol metabolic
60 of the male Wistar rats of body weight 205～225g, be divided into 6 groups at random by body weight: normal control group, high fat control group, positive controls (fenofibrate 200mg/kg) and three experimental group (pharmaceutical composition 25,50 of the present invention, 100mg/kg), every group of 10 animals.High fat diet is in administration the day before yesterday, and 6:00～7:00 gives high lipid food (prescription: 2% cholesterol, 0.2% propylthiouracil, 0.3% Sodium cholic acid, 7.5% lard, 90% normal diet) every night, replenishes normal diet daytime, altogether hello raised 12 days.Except that fenofibrate group gastric infusion, intravenous administration is 1 time during all every order 8 of each experimental group, continuous 12 days.Water is can't help in fasting in evening in last 1 day.After anaesthetizing with vetanarcol (30mg/kg) morning next day, through aorta abdominalis blood sampling and separation of serum.(1985,8 (3): the Enzymology method 142) detects triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) for yellow ability and political integrity, Chinese journal of medical examination to press document.
The result as seen, high fat control group and normal group relatively, serum TC, TG, LDL-c, TC/HDL-c and LDL-c/HDL-c all significantly raise, HDL-c then significantly descends, and shows that hyperlipidemia model duplicates successfully.Pharmaceutical composition 50 of the present invention, 100mg/kg group compare with high fat control group, can obviously reduce serum TG, LDL-c, TC/HDL-c and LDL-c/HDL-c (P＜0.05, P＜0.01 or P＜0.001), the 100mg/kg group can obviously reduce serum TC (P＜0.05) (seeing Table 7).
Table 7 pharmaceutical composition of the present invention is to the influence of hyperlipidemia rats blood lipid metabolism (x ± s, n=10) (mmol/L) (mmol/L) (mmol/L) normal control group 0.67 ± 0.24 of group TG TC LDL-c HDL-c TC/HDL-c LDL-c/HDL-c (mmol/L)
*2.98 ± 0.85
*4.25 ± 0.88
*1.10 ± 0.32
*2.71 ± 0.85
* *3.86 ± 1.32
* *High fat control group 1.14 ± 0.54 4.72 ± 1.23 7.20 ± 2.31 0.70 ± 0.31 6.74 ± 2.58 10.28 ± 3.82 experimental group 25mg/kg 0.98 ± 0.28 4.55 ± 2.02 6.14 ± 2.02 0.75 ± 0.35 6.07 ± 1.56 8.19 ± 2.5750mg/kg 0.65 ± 0.27
*4.17 ± 1.35 4.31 ± 1.33
*1.02 ± 0.27
*4.09 ± 1.76
*4.23 ± 1.78
* *100mg/kg 0.62 ± 0.35
*3.52 ± 1.01
*4.27 ± 1.32
*1.08 ± 0.19
*3.26 ± 1.39
*3.95 ± 1.45
* *Positive controls 200mg/kg 0.69 ± 0.21
*3.38 ± 1.02
*4.75 ± 1.61
*0.92 ± 0.20 3.67 ± 1.60
*5.16 ± 2.38
*
Compare with high fat control group,
*P＜0.05,
*P＜0.01,
* *P＜0.001
Claims (13)
1. produce the method for Radix Et Caulis Acanthopanacis Senticosi total saponins extractives, this method comprises the milk of lime of at first making with CaO, is alkaline with the water decoction furnishing pH value of Radix Et Caulis Acanthopanacis Senticosi; Under condition of neutral pH, make Radix Et Caulis Acanthopanacis Senticosi filtrate by macroporous adsorptive resins absorption and use ethanol elution then; Make resulting eluate by weak-type ion exchange resin and carry out routine decolouring at last again.
2 according to the process of claim 1 wherein that the pH of said milk of lime is about 10-12.
3. according to the process of claim 1 wherein that said Radix Et Caulis Acanthopanacis Senticosi is leaf and/or the stem of Radix Et Caulis Acanthopanacis Senticosi plant.
4. according to the process of claim 1 wherein that said Radix Et Caulis Acanthopanacis Senticosi is the leaf of Radix Et Caulis Acanthopanacis Senticosi plant.
5. according to the process of claim 1 wherein that the alcohol concn that is used for wash-out is about 70-95% (v/v).
6. use decolouring of weak base type resin anion(R.A) and/or activated carbon decolorizing according to the process of claim 1 wherein that said conventional decoloring method comprises.
7. according to the process of claim 1 wherein that the productive rate of said Radix Et Caulis Acanthopanacis Senticosi total saponins is 1-3% (w/w).
8. prepare the Radix Et Caulis Acanthopanacis Senticosi total saponins extractives according to each method among the claim 1-6.
9. according to the Radix Et Caulis Acanthopanacis Senticosi total saponins extractives of claim 7, wherein the purity of said Radix Et Caulis Acanthopanacis Senticosi total saponins is more than 80% (w/w).
10. the pharmaceutical composition that contains the Radix Et Caulis Acanthopanacis Senticosi total saponins extractives of with good grounds claim 7, wherein said pharmaceutical composition also contains one or more pharmaceutically acceptable carrier or vehicle except that the Radix Et Caulis Acanthopanacis Senticosi total saponins that contains as the treatment significant quantity of primary activity composition.
11. according to the pharmaceutical composition of claim 9, wherein said pharmaceutical composition is made into to be suitable for the various formulations of gi tract administration.
12. according to the pharmaceutical composition of claim 9, wherein said pharmaceutical composition is made into to be suitable for the various formulations of the outer administration of gi tract.
13. pharmaceutical composition according to claim 9, wherein said pharmaceutical composition also can contain one or more and have identical, similar or different biological active natural or synthetic other drug composition or its mixture except that the extraction of acanthopanax senticousus saponins that contains as the primary activity composition.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100446779C (en) * | 2007-06-20 | 2008-12-31 | 黑龙江省珍宝岛制药有限公司 | Method for preparing acanthopanax senticousus extracting liquid/extraction |
| CN101584719B (en) * | 2008-05-20 | 2011-11-09 | 李平亚 | Application of acanthopanax fruit extractive in preparing medicament for treating hyperlipoidemia |
| CN102526145A (en) * | 2012-02-20 | 2012-07-04 | 山东大学威海分校 | Acanthopanax senticosus leaf extract capable of protecting liver from alcoholic injury |
| CN107242353A (en) * | 2016-07-27 | 2017-10-13 | 江西中成人药业有限公司 | Stress crude granule and preparation method thereof |
| CN111374993A (en) * | 2018-12-29 | 2020-07-07 | 华北理工大学 | Method for extracting acanthopanax senticosus total saponin from acanthopanax senticosus leaves |
| CN112043739A (en) * | 2020-09-03 | 2020-12-08 | 中国人民解放军63919部队 | Application of Acanthopanax senticosus injection in the prevention of weightless cardiovascular dysfunction |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101084952B (en) * | 2006-06-08 | 2012-03-14 | 天津天士力之骄药业有限公司 | Method for preparing extraction of acanthopanax senticousus saponins |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100446779C (en) * | 2007-06-20 | 2008-12-31 | 黑龙江省珍宝岛制药有限公司 | Method for preparing acanthopanax senticousus extracting liquid/extraction |
| CN101584719B (en) * | 2008-05-20 | 2011-11-09 | 李平亚 | Application of acanthopanax fruit extractive in preparing medicament for treating hyperlipoidemia |
| CN102526145A (en) * | 2012-02-20 | 2012-07-04 | 山东大学威海分校 | Acanthopanax senticosus leaf extract capable of protecting liver from alcoholic injury |
| CN107242353A (en) * | 2016-07-27 | 2017-10-13 | 江西中成人药业有限公司 | Stress crude granule and preparation method thereof |
| CN111374993A (en) * | 2018-12-29 | 2020-07-07 | 华北理工大学 | Method for extracting acanthopanax senticosus total saponin from acanthopanax senticosus leaves |
| CN112043739A (en) * | 2020-09-03 | 2020-12-08 | 中国人民解放军63919部队 | Application of Acanthopanax senticosus injection in the prevention of weightless cardiovascular dysfunction |
| CN116173050A (en) * | 2021-11-29 | 2023-05-30 | 广东药科大学 | Application of Acanthopanax phylloside triterpene saponins in the preparation of memory enhancement preparations |
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