CN1274711C - Method of preparing general phenolic acid of red sange root for treating hepatic fibrosis - Google Patents
Method of preparing general phenolic acid of red sange root for treating hepatic fibrosis Download PDFInfo
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Abstract
The present invention relates to a method for preparing total phenolic acid of red sage root for curing hepatic fibrosis, and extract and a medicine composition prepared by using the method. The method of the present invention comprises the following steps: (1) red sage root is taken and extracted by using water, extraction liquid is filtered, and filtrate is regulated to be acidic by regulating a pH value, and filtered; (2) filtrate is processed through chromatography by using macroporous adsorption resin columns, elution by using water until effluent is neutral and has no sugar reduction reaction, then elution is carried out by using ethanol until eluate has no iron trichloride (FeCl3) reaction, and the eluate of the ethanol is collected; (3) the eluate is concentrated and dried so as to obtain total phenolic acid of red sage root.
Description
Technical field:
The present invention relates to a kind of new from salviamiltiorrhizabung the preparing salvianolic acids that is used for the treatment of hepatic fibrosis of extraction separation, and the extract and the pharmaceutical composition that make with this method.
Background technology:
China is the sick hotspot of hepatitis, and according to statistics, China chronic hepatitis virus carrier person quantity surpasses 1.3 hundred million, and the chronic viral hepatitis B patient about 3,000 ten thousand.Chronic hepatitis patient is not if in time treatment or the state of an illness fail in time that control just might not be converted into hepatic fibrosis, and hepatic fibrosis is as can not effectively being treated and control, even can develop into liver cirrhosis, liver cancer.In the market can be seldom for the clinical medicine of selecting prevention and the treatment hepatic fibrosis that causes of chronic hepatitis or early stage liver cirrhosis for use, and mostly uncertain therapeutic efficacy cut and toxic side effect bigger.
Radix Salviae Miltiorrhizae total phenolic acids is a red sage root water soluble ingredient, and modern pharmacological research shows, Radix Salviae Miltiorrhizae total phenolic acids is as the water soluble component of the red sage root, to liver cell because of tetracol phenixin (CCl
4) or the liver injury model that D-galactosamine brought out significant provide protection is arranged; To CCl
4The rat liver fibrosis model that brings out has significant provide protection, and its anti-hepatic fibrosis intensity is better than colchicine; In the rat hepatocirrhosis pathological model, can promote the heavily absorption of established collegen filament degraded and liver fiber.Therefore, use modernism, extraction separation goes out the efficient part based on Radix Salviae Miltiorrhizae total phenolic acids from the red sage root, and makes suitable dosage forms, will go up significant in treatment chronic hepatitis hepatic fibrosis (early stage liver cirrhosis).
The extracting method that bibliographical information salvianolate and salvianolic acid B salt are arranged at present, the composition of its acquisition is the saline admixture of Radix Salviae Miltiorrhizae total phenolic acids, the extraction cost height, yield is low, and content is relatively low, less stable.
Chinese patent (publication number CN1459448) discloses preparing salvianolic acids and uses thereof, polyamide column chromatography method and macroporous resin column chromatography method in its preparation technology, have successively been adopted, not only operating process is loaded down with trivial details, length consuming time, and the samples contg that obtains is not high, because the regenerative process of polymeric amide is very difficult, life cycle is short simultaneously, therefore production cost is very high, is not suitable for industrialized production.In addition, research also shows, salvianolic acid is extremely unstable in basic solution, obviously be irrational with adding the buck wash-out behind the polyamide column on the Radix Salviae Miltiorrhizae extract in this technology, a large amount of phenolic acid are destroyed, bring the decomposition by-products of salvianolic acid simultaneously into, not only be unfavorable for improving the content of salvianolic acid, and bring hidden danger can for the security of medicine.
Chinese patent (publication number CN1384090) discloses the method for making and the purposes of the extracting method and the preparation thereof of Radix Salviae Miltiorrhizae total phenolic acids, the method that has adopted traditional water extract-alcohol precipitation and alkali to transfer in its technology, because being the form with salt in plant materials, salvianolic acid exists, so solubleness is very little in ethanol, in the process of alcohol precipitation, the all precipitated removal of a large amount of salvianolic acid, therefore the aqueous extraction-alcohol precipitation technology of the red sage root is to be proved to be backward technology at present, except in some reds sage root compound preparation early, using, substantially be eliminated, according to said method not only yield is low for Zhi Bei Radix Salviae Miltiorrhizae total phenolic acids, and character is also very unstable.
Summary of the invention:
The purpose of this invention is to provide a kind of from salviamiltiorrhizabung the extraction separation preparing salvianolic acids.This method can improve the utilization ratio of red rooted salvia greatly, the natural resources of Chinese medicinal materials of saves valuable, and overcome the deficiencies in the prior art, and the content of Radix Salviae Miltiorrhizae total phenolic acids and stability are improved greatly, good process repeatability is simple and easy to do simultaneously, is fit to suitability for industrialized production.
Method of the present invention, the process following steps:
(1) get red rooted salvia, use water extraction, extracting liquid filtering, filtrate transfers pH to acid, filters;
(2) filtrate is used macroporous adsorbent resin column chromatography, the water wash-out, to effluent liquid for neutral and do not have reducing sugar reaction after, use ethanol elution again, do not have iron trichloride (FeCl to elutriant
3) reaction, collect ethanol eluate;
(3) elutriant concentrates, and drying promptly gets Radix Salviae Miltiorrhizae total phenolic acids.
Method of the present invention, preferably pass through following steps:
(1) get red rooted salvia, be cut into segment or pulverizing, add hot water extraction, after extracting solution is taken advantage of heat filtering, put coldly, filtrate adds acid and transfers pH to acid, filters;
(2) macroporous adsorptive resins on the filtrate, water fully are eluted to effluent liquid for neutrality and after not having reducing sugar reaction, do not have iron trichloride (FeCl with ethanol elution to elutriant again
3) reaction, collect elutriant;
(3) the elutriant reclaim under reduced pressure is to doing, and drying promptly gets Radix Salviae Miltiorrhizae total phenolic acids.
In aforesaid method, in the step (1), water extraction can be used hot water, and amount of water is 6～8 times of the red sage root, extracts 2～3 times, and each 0.5～1 hour, the hot water temperature was 60～100 ℃, and the best is 60-80 ℃.Filtrate adds acid and transfers pH to 2.0～6.0, and the best is 3.5～5.0, and acid can be hydrochloric acid, sulfuric acid, phosphoric acid etc., is preferably hydrochloric acid, make salvianolic acid fully be converted into single free phenolic acid form from the form of multiple salt after, filter.In the step (2), adopt the Semi-polarity macroporous adsorptive resins preferable, Semi-polarity macroporous adsorptive resins model is HPD-400, D101, D-1300 or AB-8 type etc.The alcohol concn of wash-out can be 30-100%, and the best is 50～75% ethanol.
Contain the Radix Salviae Miltiorrhizae total phenolic acids extract through what preparation method of the present invention made, wherein the content of Radix Salviae Miltiorrhizae total phenolic acids is greater than 90%, and wherein the content of salvianolic acid B is greater than 50%.
The present invention also provides the pharmaceutical composition that contains Radix Salviae Miltiorrhizae total phenolic acids extract of the present invention, said composition contains the Radix Salviae Miltiorrhizae total phenolic acids extract and the acceptable accessories of significant quantity on the physiology, and said composition can be any pharmaceutical dosage forms of Gong taking.
The present invention also comprises with Radix Salviae Miltiorrhizae total phenolic acids extract of the present invention or its pharmaceutical composition and treats and/or prevents application in the medicine of hepatic fibrosis in preparation.
The dosage form that is fit to take that pharmaceutical composition of the present invention can be made into is selected from: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, sublimed preparation, suspensoid, pulvis, injection of solution agent, exsiccant powder injection.
Drug combination preparation of the present invention is taken in a conventional manner, comprise oral and injection to keep the activity of medicine.
Pharmaceutical preparation of the present invention can add when making preparation and physiologically acceptable carrier (auxiliary material).Described physiologically acceptable carrier is selected from following material: N.F,USP MANNITOL, sorbyl alcohol, Sodium Pyrosulfite, sodium bisulfite, Sulfothiorine, cysteine hydrochloride, Thiovanic acid, methionine(Met), vitamins C, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphoric acid salt or its aqueous solution, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acid, sodium-chlor, Repone K, Sodium.alpha.-hydroxypropionate, Xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, Mierocrystalline cellulose and derivative thereof, alginate, gelatin, polyvinylpyrrolidone, glycerine, soil temperature 80, agar, lime carbonate, Calcium hydrogen carbonate, tensio-active agent, polyoxyethylene glycol, cyclodextrin, beta-cyclodextrin, the phospholipid material, kaolin, talcum powder, calcium stearate, Magnesium Stearate etc.
Preparation of the present invention if oral, contains vehicle commonly used, such as tackiness agent, weighting agent, thinner, lubricant, disintegrating agent, tinting material, seasonings, wetting agent, sanitas, solubility promoter.
The weighting agent that is suitable for comprises Mierocrystalline cellulose, mannitol, lactose and other similar weighting agent.Suitable disintegrating agent comprises starch, polyvinylpyrrolidone and starch derivative, for example sodium starch glycollate.Suitable lubricant comprises, for example Magnesium Stearate, talcum powder.The acceptable wetting agent of appropriate drug comprises sodium lauryl sulphate.
Can fill by mixing, the method that compressing tablet etc. are commonly used prepares solid oral composition.Mix repeatedly activeconstituents is distributed in those preparations of a large amount of weighting agents of whole use.
The form of oral liquid for example can be water-based or oily suspensions, solution, emulsion, syrup or elixir, perhaps can be a kind of used water before use or other suitable composite drying products of carrier.This liquid preparation can contain conventional additive, such as suspension agent, for example sorbyl alcohol, syrup, methylcellulose gum, gelatin, Natvosol, carboxymethyl cellulose, aluminium stearate gel or hydrogenation edible-fat, emulsifying agent, for example Yelkin TTS, anhydro sorbitol monooleate or gum arabic; Non-aqueous carrier (they can comprise edible oil), for example Prunus amygdalus oil, fractionated coconut oil, such as oily ester, propylene glycol or the ethanol of the ester of glycerine; Sanitas, for example para hydroxybenzene methyl esters or propylparaben or Sorbic Acid, and if desired, can contain conventional flavouring agent or tinting material.
For injection, the liquid unit dosage of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, this compound can be suspended or dissolving.The preparation of solution is normally passed through medicine dissolution in a kind of carrier, filter-sterilized before it is packed into a kind of suitable bottle or ampoule, sealing then.For example a kind of local anesthetic of auxiliary material, sanitas and buffer reagent also can be dissolved in this carrier.In order to improve its stability, can be after the bottle of packing into that this composition is freezing, and under vacuum, water is removed.
Prepare parenteral suspension with essentially identical mode,, and before it is suspended in sterile carrier, it is carried out disinfection with oxyethane except being is suspended in carrier with active compound rather than with its dissolving.Tensio-active agent or wetting agent can be included in this preparation, are beneficial to the uniform distribution of this active compound.
Pharmaceutical preparation of the present invention, preferably tablet or capsule preparations, each sheet/grain contains 1-1000mg Radix Salviae Miltiorrhizae total phenolic acids extract of the present invention, preferred 100mg Radix Salviae Miltiorrhizae total phenolic acids extract of the present invention, all the other are the medicine acceptable carrier.
The present invention compared with prior art has tangible advantage:
(1) salvianolic acid in the red rooted salvia mainly is that form with multiple salt exists, and is mainly magnesium salts, ammonium sylvite etc., and salvianolic acid has and face two phenolic hydroxyl groups, and very easily oxidized, stability is very poor; Also there are simultaneously compositions such as a large amount of polyoses, protein-based, tanshinone in the red sage root.Result of the present invention shows, the salviol hydrochlorate is converted into after the free acid, and salvianolic acid stability improves greatly, and acidification has simultaneously also been removed the polyose in the red sage root, impurity such as protein-based greatly, and curative effect increases.
(2) salvianolic acid salt constituents is difficult to by the macroporous resin adsorption purifying, then can well be adsorbed by macroporous resin through the free salvianolic acid after the soda acid conversion among the present invention, thereby can be purified removal of impurities.
(3) the macroporous resin purification technology of the present invention's employing, Radix Salviae Miltiorrhizae total phenolic acids yield height, content height that separation and purification obtains, wherein the content of Radix Salviae Miltiorrhizae total phenolic acids is greater than 90%, by big production checking, the average content of each batch sample is 98.5%, wherein the content of salvianolic acid B surpasses 50%, and yield is greater than 4%.The present invention improves the utilization ratio of red rooted salvia greatly, the natural resources of Chinese medicinal materials of saves valuable,
(4) the present invention is easy and simple to handle, has reduced cost, and very is fit to suitability for industrialized production.
The animal test of pesticide effectiveness below by Radix Salviae Miltiorrhizae total phenolic acids further specifies beneficial effect of the present invention.
1, Radix Salviae Miltiorrhizae total phenolic acids of the present invention is to CCl
4Cause the influence of rat liver fibrosis model:
1.1 the model preparation: 110 rat random packet, except that normal group, all the other respectively organize rat first with pure CCl
40.5ml/100g body weight is later on 40% CCl
4Olive oil solution 0.3ml/100g body weight, in the subcutaneous injection of rat back rear side, weekly twice, to the 4th week, the 5th week the back with 20% CCl
4Olive oil solution 0.15ml/100g body weight, with the method subcutaneous injection, weekly twice, to the 12nd week.Raise in the 1-2 week of modeling with high fat Semen Maydis powder feed (80% Semen Maydis powder, 20% lard, 0.5% cholesterol), raise with normal diet after the 3rd week; Freely drink water.Normal rats is fed with normal diet.
1.2 administration: from the 5th week, administration group rat is irritated stomach respectively every day and gives Radix Salviae Miltiorrhizae total phenolic acids 25,50,100mg/kg, and positive controls is irritated stomach and give Malotilate 100mg/kg every day, to the 13rd week.The serum biochemistry index is surveyed in blood sampling in 1 hour after the last administration, gets liver, spleen is weighed.A hepatic tissue part is made liver homogenate, is used to measure level of lipid and hydroxyproline content; All the other hepatic tissues are fixed with 10% formalin solution, specimens paraffin embedding slices, and HE dyeing is used for histopathological examination.According to every kind of lesion degree, be designated as "-", "+", " ++ ", " +++", be converted into respectively 0,1,2,3 fen, calculate every group average product score value.
1.3 the inspection of serum biochemistry index, hepatic tissue level of lipid and hydroxyproline content are measured: albumin (Alb), the green colorimetry of bromine potassium phenol; Total protein (TP) is examined Ma Shi light blue method; Aspartic Acid transaminase (AST), alanine aminotransferase (ALT), reitman-frankel method; All undertaken by the test kit specification sheets.The mensuration of superoxide-dismutase (SOD), mda (MDA), gsh (GSH), Selenoperoxidase (GSH-PX), oxyproline (Hyp) is all undertaken by the test kit specification sheets.
1.4 test-results
1.4.1 influence to rat body weight, liver spleen changes in weight
As shown in table 1, the model group rat body weight alleviates, hepatosplenomegaly, and the liver spleen index obviously increases, and the medicine group has the trend of recovery.
Table 1 Radix Salviae Miltiorrhizae total phenolic acids is to CCl
4The influence of liver fibrosis due rat body weight, liver spleen weight (X ± SD)
| Group | Dosage (mg/kg) | Number of animals (only) | Body weight (g) | Liver heavy (g) | Liver index (mg/g) | Spleen heavy (g) | Spleen index (mg/g) |
| The normal group model control group | - - | 10 18 | 340±93 315±78 | 9.0±1.8 9.8±1.3 | 27.1±4.4 32.1±5.2 * | 0.55±0.13 0.83±0.48 | 1.6±0.2 2.7±1.6 * |
| Dosage group salvianolic acid high dose group Malotilate group in the salvianolic acid low dose group salvianolic acid | 25 50 100 100 | 18 18 13 16 | 317±77 314±72 335±78 324±52 | 9.1±1.9 9.2±1.4 9.9±1.6 10.1±2.0 | 29.4±5.9 30.1±5.1 30.2±3.5 31.2±2.8 | 0.78±0.6 0.72±0.19 0.88±0.44 0.72±0.25 | 2.7±3.1 2.3±0.4 2.6±1.1 2.2±0.8 |
*P＜0.05,
*P＜0.01 is compared with normal group;
#P＜0.05,
##P＜0.01 is compared with control group.
1.4.2 influence to the rat blood serum biochemical indicator
As shown in table 2, rat model albumin, total protein and white/ball ratio all significantly descend, and salvianolic acid low dose group and Malotilate group dialogue/ball ratio have the trend of recovery, and the dosage group has then improved in vain/ball ratio significantly in the salvianolic acid.
Table 2 Radix Salviae Miltiorrhizae total phenolic acids is to CCl
4The influence of liver fibrosis due rat blood serum biochemical indicator (X ± SD)
| Group | Dosage (mg/kg) | Number of animals (only) | ALT (Karmen Unit) | AST (Karmen Unit) | Alb (mg/ml) | TP (mg/ml) | A/G ratio |
| Dosage group salvianolic acid high dose group Malotilate group in the normal group model control group salvianolic acid low dose group salvianolic acid | - - 25 50 100 100 | 10 18 18 18 13 16 | 20.7±13.7 27.3±11.6 25.5±14.5 24.2±15.3 27.5±18.9 27.2±14.4 | 114.5±16.9 104.9±22.0 110.8±16.0 107.8±24.2 103.3±20.9 121.5±29.0 | 35.3±10.8 27.5±6.5 * 27.0±7.6 30.3±10.6 25±3.5 29.5±9.4 | 118.0±25.8 97.3±20.0 * 89.6±17.2 85.3±18.1 91.1±17.1 92.9±20.7 | 0.524±0.382 0.406±0.096 0.455±0.175 0.588±0.275 # 0.393±0.092 0.487±0.188 |
*P＜0.05,
*P＜0.01 is compared with normal group;
#P＜0.05,
##＜0.01, compare with control group.
From above result as can be known, for CCl
4Inductive rat liver fibrosis model, Radix Salviae Miltiorrhizae total phenolic acids can make oxyproline in the hepatic tissue (Hyp) content descend, Selenoperoxidase (GSH-PX) and superoxide dismutase (SOD) content raise, and the result of histopathologic examination shows that also salvianolic acid can make CCl
4The fibrosis of Liver Fibrosis Model rat alleviates, and hepatic cell fattydegeneration is alleviated, and liver lobule structure deteriorate degree alleviates, and pseudolobuli forms and reduces, and connective tissue proliferation alleviates.Results suggest, salvianolic acid have tangible anti hepatic fibrosis.
Embodiment:
The following example is intended to further describe for example practicality of the present invention, rather than limits the present invention by any way.
Detection method:
Test materials: the red sage root, available from the Haozhou, Anhui, the place of production is Anhui; The salvianolic acid B reference substance, self-control, content is greater than 98.5%.
Detection method:
1. Radix Salviae Miltiorrhizae total phenolic acids
The preparation precision of reference substance solution takes by weighing through 60 ℃ of drying under reduced pressure an amount of to the salvianolic acid B reference substance of constant weight, adds methyl alcohol and makes the solution that every 1ml contains 25 μ g, promptly.
The about 25mg of this product is got in the preparation of need testing solution, accurate claims surely, puts in the measuring bottle of 25ml, with dissolve with methanol and be diluted to scale, shakes up, and filters; Precision is measured subsequent filtrate 3ml, puts in the measuring bottle of 100ml, adds methyl alcohol and is diluted to scale, shakes up, promptly.
Assay method gets reference substance solution respectively and need testing solution is an amount of, measures optical density respectively at 287nm wavelength place according to ultraviolet spectrophotometry (appendix VA of Chinese Pharmacopoeia version in 2000), calculates, promptly.
2. salvianolic acid B
Measure according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000).
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is weighting agent; With methanol-water-Glacial acetic acid (40: 60: 0.5, include the 3mmol/L Tetrabutyl amonium bromide) is moving phase, flow velocity 1.0ml/min; Detect wavelength: 285nm.Number of theoretical plate calculates by salvianolic acid B should be not less than 3000.
The preparation of reference substance solution: precision takes by weighing through 60 ℃ of drying under reduced pressure an amount of to the salvianolic acid B reference substance of constant weight, adds the moving phase dissolving and makes the solution that every 1ml contains 50 μ g, promptly.
The preparation of need testing solution: get the about 25mg of this product, the accurate title, decide, and places the measuring bottle of 25ml, adds the moving phase dissolving and be diluted to scale, shakes up, and filters, and precision is measured subsequent filtrate 5ml, puts in the measuring bottle of 50ml, adds moving phase and is diluted to scale, shakes up, promptly.
Assay method: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject liquid chromatograph, measure, promptly.
Embodiment 1:
Get red rooted salvia 100kg, the water that adds 6 times of amounts extracts 2 times in 60 ℃, each 1 hour, after extracting solution is taken advantage of heat filtering, put coldly, filtrate adds hydrochloric acid and transfers pH to 2.0, filters the back and goes up the AB-8 macroporous adsorptive resins, water fully be eluted to effluent liquid for neutral and do not have reducing sugar reaction after, do not have FeCl with 30% ethanol elution to elutriant again
3Reaction is collected elutriant and is recycled to driedly, and drying promptly gets salvianolic acid 4.1kg.
After measured, total phenolic content content is 98.5% in the above-mentioned salvianolic acid, and wherein content of danshinolic acid B 67.9%.
Embodiment 2:
Get red rooted salvia 100kg, the water that adds 8 times of amounts extracts 2 times in 80 ℃, each 1 hour, after extracting solution is taken advantage of heat filtering, put coldly, filtrate adds hydrochloric acid and transfers pH to 4.5, filters the back and goes up the HPD-400 macroporous adsorptive resins, water fully be eluted to effluent liquid for neutral and do not have reducing sugar reaction after, do not have FeCl with 60% ethanol elution to elutriant again
3Reaction is collected elutriant and is recycled to driedly, and drying promptly gets salvianolic acid 4.3kg.
After measured, total phenolic content is 99.6% in the above-mentioned salvianolic acid, and wherein content of danshinolic acid B 71.3%.
Embodiment 3:
Get red rooted salvia 150kg, the water that adds 8 times of amounts extracts 3 times in 80 ℃, each 0.5 hour, after extracting solution is taken advantage of heat filtering, put coldly, filtrate adds hydrochloric acid and transfers pH to 5.0, filters the back and goes up the D-101 macroporous adsorptive resins, water fully be eluted to effluent liquid for neutral and do not have reducing sugar reaction after, do not have FeCl with 75% ethanol elution to elutriant again
3Reaction is collected elutriant and is recycled to driedly, and drying promptly gets salvianolic acid 6.4kg.
After measured, total phenolic content is 97.9% in the above-mentioned salvianolic acid, and wherein content of danshinolic acid B 59.1%.
Embodiment 4:
Get red rooted salvia 120kg, the water that adds 8 times of amounts extracts 2 times in 100 ℃, each 1 hour, after extracting solution is taken advantage of heat filtering, put coldly, filtrate adds hydrochloric acid and transfers pH to 6.0, filters the back and goes up the D-1300 macroporous adsorptive resins, water fully be eluted to effluent liquid for neutral and do not have reducing sugar reaction after, do not have FeCl with 100% ethanol elution to elutriant again
3Reaction is collected elutriant and is recycled to driedly, and drying promptly gets salvianolic acid 5.1kg.
After measured, total phenolic content is 99.1% in the above-mentioned salvianolic acid, and wherein content of danshinolic acid B 76.6%.
Embodiment 5
Every preparation that contains the tablet of 100mg salvianolic acid extract
Get the salvianolic acid extract 100g that embodiment 1 method obtains, add starch 50g, carboxymethyl cellulose 50g, mix with the progression method, 75% ethanol is wetting agent, mixing, wet granulation, oven dry, whole grain, add 1% magnesium stearate, the mixing compressing tablet extrudes 1000.
Embodiment 6
Every capsular preparation that contains 100mg salvianolic acid extract
Get the salvianolic acid extract 100g that embodiment 1 method obtains, add starch 50g, carboxymethyl cellulose 50g, mix with the progression method, 75% ethanol is wetting agent, mixing, wet granulation, oven dry, whole grain add 1% magnesium stearate, encapsulated 1000 of mixing.
Claims (6)
1, a kind of Radix Salviae Miltiorrhizae total phenolic acids extract is characterized in that, the content of Radix Salviae Miltiorrhizae total phenolic acids is greater than 90%, and the content of salvianolic acid B is greater than 50% and smaller or equal to 76.6%.
2, the described Radix Salviae Miltiorrhizae total phenolic acids extract of claim 1 is as the pharmaceutical composition of active constituents of medicine.
3, the described composition of claim 2, its pharmaceutical dosage forms is selected from: tablet, capsule, dripping pill, injection liquid or powder injection.
4, described Radix Salviae Miltiorrhizae total phenolic acids extract of claim 1 or the described pharmaceutical composition of claim 2 treat and/or prevent application in the hepatic fibrosis medicines in preparation.
5, the Radix Salviae Miltiorrhizae total phenolic acids preparation method of extract of claim 1 is characterized in that through following steps:
(1) getting red rooted salvia, is 60～80 ℃ hot water extraction 2～3 times with temperature, each 0.5～1 hour, and extracting liquid filtering, filter filtrate adjust pH to 3.5～5.0;
(2) filtrate is used the Semi-polarity macroporous adsorbent resin column chromatography, water be eluted to effluent liquid for neutral and do not have reducing sugar reaction after, use 50～75% ethanol elutions again, do not have ferric chloride reaction to elutriant, collect ethanol eluate, wherein the Semi-polarity macroporous adsorbent resin is selected from HPD-400 or AB-8 type;
(3) elutriant concentrates, and drying promptly gets the Radix Salviae Miltiorrhizae total phenolic acids extract.
6, preparation method according to claim 5 wherein regulates pH and selects for use: hydrochloric acid, sulfuric acid or phosphoric acid.
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| CN101292986B (en) * | 2007-04-29 | 2010-09-08 | 北京本草天源药物研究院 | Pharmaceutical composition |
| CN101095720B (en) * | 2007-07-16 | 2011-04-06 | 正大青春宝药业有限公司 | Method for preparing total salvianolic acid and the application in the preventing and treating of diabetes and the complication thereof |
| CN101574411B (en) * | 2009-06-08 | 2011-11-30 | 沈阳亿灵医药科技有限公司 | Shuang dan orally disintegrating tablet |
| CN103191186A (en) * | 2012-01-04 | 2013-07-10 | 天士力制药集团股份有限公司 | Application of salvia miltiorrhiza preparation in preparing anti-liver-fibrosis medicines |
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