CN1977888B - Medicinal composition of baicalin, ganoderma lucidum and salvia miltrorrhiza - Google Patents
Medicinal composition of baicalin, ganoderma lucidum and salvia miltrorrhiza Download PDFInfo
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- CN1977888B CN1977888B CN2005100454113A CN200510045411A CN1977888B CN 1977888 B CN1977888 B CN 1977888B CN 2005100454113 A CN2005100454113 A CN 2005100454113A CN 200510045411 A CN200510045411 A CN 200510045411A CN 1977888 B CN1977888 B CN 1977888B
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Abstract
The present invention discloses a medicine composition and its preparation method. Said medicine composition is formed from (by weight portion) 50-1250 portions of baicalin, 500-24000 portions of ganoderma and 1000-90000 portions of salvia root. Said medicine composition also can be made up by using 50-1250 portions of baicalin, 7.5-360 portions of ganoderma polysaccharide and 30-1800 portions of salvia total phenolic acid. Said medicine composition can be made into various dosage forms, and can be used for curing various acute and chronic hepatitides.
Description
1, technical field
The present invention relates to a kind of pharmaceutical composition of processing by baicalin, Ganoderma or its extract and Radix Salviae Miltiorrhizae or its extract that is used to treat hepatitis, and preparation method thereof, medical technical field belonged to.
2, background technology
Hepatitis is commonly encountered diseases, the frequently-occurring disease of a kind of serious harm human health and life, and sickness rate is high in China, according to relevant expert's preresearch estimates, and the annual nearly hepatitis patient 3,000 ten thousand of China, more than 100,000,000 hepatitis B virus carriers.At present domestic diagnostic means to hepatitis is advanced, but treatment does not still have specific medicament, and therefore the medicine of exploitation treatment hepatitis is still the problem that presses for solution.
Baicalin is a kind of flavone compound that from Chinese crude drug Radix Scutellariae (Scutellariabaicalensis georgi), extracts; Recorded into the 10th 239 pages of national drug standards chemical drugs provincial standard rising national standards of National Drug Administration (Chinese Pharmacopoeia Commission's volume); Wherein regulation is pressed dry product calculating, contains baicalin (C
21H
18O
11) must not be less than 90.0% (injection); Must not be less than 83.0% (pro ore).The baicalin raw material is at present domestic to have a plurality of manufacturer production to go on the market.Baicalin has pharmacological action widely, and main pharmacological has: (1) antibacterial action.Baicalin is an antibacterial activity composition main in the Radix Scutellariae, and has a broad antifungal spectrum can suppress the breeding and the growth of various bacteria.(2) antiinflammatory action.Pair antihistaminic is arranged, and the inflammation-inhibiting edema reduces the effect of capillary permeability, can the inflammation-inhibiting reaction red, swollen, hot, bitterly.(3) diuresis.Can improve the urine formation speed of laboratory animal.(4) hypotensive effect.Can cause the blood pressure drops of kinds of experiments animal.(5) hepatoprotective effect.These article have significant protective effect to hbs antigen, e antigen, cAg, and hepatitis B virus DNA is duplicated also has inhibitory action; Can significantly reduce glutamate pyruvate transaminase after the medication, liver is had the better protect effect.The effect of these article glutamate pyruvate transaminase lowering is better, and visible hepatitis b surface antigen positive degree descends during the medication, but does not consolidate.
Ganoderma is Polyporaceae fungus Ganoderma lucidum (Leyss. Ex Fr.) Karst. Ganoderma lucidum (Ley-ss.ex Fr.) Karst. or Ganoderma Ganoderma sinense Zhao, the dry sporophore of Xu et Zhang.The property sweet, flat, GUIXIN, lung, liver, kidney channel.Have invigorating QI and tranquilization, the effect of relieving cough and asthma is mainly used in dizzy sleeplessness, shortness of breath and palpitation, cough due to consumptive disease.Ganoderma is widely known Chinese medicine, is commonly called as " Herba mesonae chinensis ".Beginning is stated from Shennong's Herbal, and " tonifying liver QI invigorating " " the hard muscles and bones " that be considered to can " the beneficial motive " " to pacify smart soul " classified as top grade.Compendium of Material Medica thinks that Ganoderma has " strengthening by means of tonics " " life lengthening " " sharp joint " effects such as " controlling deafness ".Ganoderma can strengthening the body resistance, raise immunity, and human body immunity improving power, two-ways regulation function of human body balance is regulated the internal body vigor on the whole, regulates human body metabolism function, improves autoimmunity, promotes internal organs or organ function normalization.The main effective ingredient of Ganoderma is a ganoderan, and ganoderan has the effect of significant enhance immunity.
Radix Salviae Miltiorrhizae is the dry root and rhizome of labiate Radix Salviae Miltiorrhizae Salvia miltiorrhiza Bage..Bitter in the mouth, cold nature, GUIXIN, Liver Channel have stasis-dispelling and pain-killing, promoting blood circulation to restore menstrual flow, an effect of the relieving restlessness that clears away heart-fire.Radix Salviae Miltiorrhizae mainly comprises in the mechanism of action aspect the treatment chronic hepatitis B; (1) removing pathogenic heat from blood and toxic substance from the body anti-inflammation alleviates or eliminates the liver parenchyma inflammation, helps liver to recover function of detoxification simultaneously; (2) improve the circulation of liver inner blood, correct the microcirculation disturbance of liver, blood circulation promoting and blood stasis dispelling makes liver and spleen retraction; (3) adjustment body's immunity is eliminated the infringement of immune complex to liver; (4) promote liver cell regeneration, anti-hepatic fibrosis; (5) recovering liver function.Red sage root water soluble ingredient mainly is to be the phenolic acid compound of basic structure with the danshensu, and the Radix Salviae Miltiorrhizae total phenolic acids chemical compound has very strong antioxidation, can remove superoxide anion and hydroxy radical, suppresses lipid peroxidation, and then alleviates hepatic injury.
At present, utilize the interaction of baicalin, Ganoderma and Radix Salviae Miltiorrhizae, composition of prescription, preparation is used to treat the medicine of acute, chronic hepatitis, does not appear in the newspapers as yet.
3, summary of the invention
In order to meet clinical needs, treat hepatitis better, improve the people ' s health level, the invention provides a kind of new pharmaceutical composition and preparation method thereof.
Pharmaceutical composition of the present invention is mainly processed by baicalin, Ganoderma and Radix Salviae Miltiorrhizae, and three's weight proportion is: 50～1250 parts of baicalins, 500～24000 parts of Ganodermas, 1000～90000 parts of Radix Salviae Miltiorrhizaes; Be preferably: 125～500 parts of baicalins, 8000～32000 parts of Ganodermas, 5000～45000 parts of Radix Salviae Miltiorrhizaes; 250 parts of baicalins, 6000 parts of Ganodermas, 15000 parts of Radix Salviae Miltiorrhizaes.
Ganoderma in the pharmaceutical composition of the present invention and Radix Salviae Miltiorrhizae can prepare extract with The suitable solvent and method; Total extract is processed arbitrary preparation with baicalin and mixing acceptable accessories again, and main effective ingredient contained in the total extract is: ganoderan and Radix Salviae Miltiorrhizae total phenolic acids.Total extract content preferably is not less than 30%.
Ganoderma can obtain ganoderan through extracting processing with The suitable solvent, extracts solvent and is preferably water or ethanol, and the method for distilling of Ganoderma can be infusion process, percolation, decocting method, reflux extraction or continuous extraction.As can prepare ganoderan through the method for water extract-alcohol precipitation, can also be through preparing according to literature method.
Be that the preparation technology of Ganoderma of main effective ingredient is following with polysaccharide in the present composition:
Get the Ganoderma medical material, be ground into coarse grain, add the moistening of 3 times of amounts of water and spend the night, decoct next day three times, added 12 times of amounts of water for the first time in 3 hours, added 10 times of amounts of water for the second time in 2 hours; Added 10 times of amounts of water in 1 hour for the third time, collecting decoction filters, and it is 1.02～1.06 that filtrating is concentrated into relative density, puts coldly, adds ethanol and makes that to contain the alcohol amount be 65%; Stir, placed 24 hours at 4 ℃, filter, filtrate recycling ethanol filters to there not being the alcohol flavor; Add ethanol and make that to contain alcohol amount be 80%, stir, placed 24 hours at 4 ℃, filter, filtrate recycling ethanol is to there not being the alcohol flavor; Placed 48 hours at 4 ℃, filter, filtrating is concentrated into the thick paste shape, and spray drying promptly gets.
Content through polysaccharide in the ganoderan of this prepared is not less than 50%, and yield is 0.5～3%.
Except that adopting above-mentioned technology, Ganoderma also can be through following prepared, but is not limited only to following technology:
Technology one: get the Ganoderma medical material, be ground into coarse grain, decocte with water three times added 12 times of amounts of water in 3 hours for the first time, and second and third time added 10 times of amounts of water in 2 hours; Collecting decoction filters, and it is 1.03～1.08 that filtrating is concentrated into relative density, puts coldly, adds ethanol and makes that to contain the alcohol amount be 65%; Stir, placed 24 hours at 4 ℃, filter, filtrate recycling ethanol filters to there not being the alcohol flavor; Add ethanol and make that to contain alcohol amount be 80%, stir, placed 24 hours at 4 ℃, filter, filtrate recycling ethanol is to there not being the alcohol flavor; Placed 48 hours at 4 ℃, filter, filtrating is concentrated into the thick paste shape, and spray drying promptly gets.Content through polysaccharide in the ganoderan of this prepared is not less than 30%, and yield is 5～8%.
Technology two: get the Ganoderma medical material, be ground into coarse grain, add the moistening of 3 times of amounts of water and spend the night, decoct secondary next day, added 12 times of amounts of water for the first time in 3 hours, added 10 times of amounts of water for the second time in 2 hours; Collecting decoction filters, and it is 1.02～1.06 that filtrating is concentrated into relative density, puts coldly, adds ethanol and makes that to contain the alcohol amount be 70%; Stir, placed 24 hours at 4 ℃, filter, filtrate recycling ethanol filters to there not being the alcohol flavor; Add ethanol and make that to contain alcohol amount be 85%, stir, placed 24 hours at 4 ℃, filter, filtrate recycling ethanol is to there not being the alcohol flavor; Placed 48 hours at 4 ℃, filter, filtrating is concentrated into the thick paste shape, and spray drying promptly gets.Content through ganoderan in the ganoderan of this prepared is not less than 40%, and yield is 3～6%.
Radix Salviae Miltiorrhizae can obtain Radix Salviae Miltiorrhizae total phenolic acids through extracting processing with The suitable solvent, extracts solvent preferred water or ethanol, and the method for distilling of Radix Salviae Miltiorrhizae can be infusion process, percolation, decocting method, reflux extraction or continuous extraction.As can prepare Radix Salviae Miltiorrhizae total phenolic acids through the method for water extract-alcohol precipitation, can also be through preparing according to literature method.
Be that the preferred for preparation technology of Radix Salviae Miltiorrhizae of main effective ingredient is following with Radix Salviae Miltiorrhizae total phenolic acids in the pharmaceutical composition of the present invention:
Get Radix Salviae Miltiorrhizae, be ground into coarse grain, decocte with water three times, 2 hours for the first time, add 12 times of amounts of water, second and third time each 1.5 hours adds 10 times of amounts of water, and collecting decoction filters, and it is 1.17～1.20 (80 ℃) that filtrate decompression is concentrated into relative density.Add the ethanol precipitation secondary, make for the first time that to contain the alcohol amount be 75%, make that to contain the alcohol amount be 85% for the second time, respectively leave standstill 24h, reclaiming ethanol to relative density is 1.17～1.20 (80 ℃ of surveys), and spray drying promptly gets.
Radix Salviae Miltiorrhizae total phenolic acids yield through this prepared is 1～3%, and the content of Radix Salviae Miltiorrhizae total phenolic acids is not less than 50%, and the content of salvianolic acid B is not less than 1.5%.
Radix Salviae Miltiorrhizae also can be through following prepared, but is not limited only to following technology:
Technology one: get Radix Salviae Miltiorrhizae, decocte with water twice each 2 hours, adds 12 times of amounts of water for the first time; For the second time add 10 times of amounts of water, collecting decoction filters; To be concentrated into relative density be 1.17～1.20 (80 ℃) to filtrating, adds ethanol precipitation and make and contain the alcohol amount and reach 75%, leaves standstill 24h; Reclaiming ethanol to relative density is 1.23～1.28 (80 ℃), and vacuum drying (50 ℃) promptly gets.Through the Radix Salviae Miltiorrhizae total phenolic acids yield 2～4% of this prepared, the content of Radix Salviae Miltiorrhizae total phenolic acids is not less than 40%, and the content of salvianolic acid B is not less than 0.8%.
Technology two: get Radix Salviae Miltiorrhizae, add 85% alcohol reflux 2 hours, filter, decompression filtrate recycling ethanol is to thick paste; Medicinal residues add water (10 times of amounts) decoction 1 hour, filter, and filtrating merges with above-mentioned thick paste, are evaporated in right amount, and 50 ℃ of vacuum dryings are pulverized, and sieve, and promptly get.Radix Salviae Miltiorrhizae total phenolic acids yield through this prepared is 3～5%, and the content of Radix Salviae Miltiorrhizae total phenolic acids is not less than 30%, and the content of salvianolic acid B is not less than 0.3%.
Aforementioned pharmaceutical compositions can also replace Ganoderma, Radix Salviae Miltiorrhizae total phenolic acids to replace Radix Salviae Miltiorrhizae to feed intake with ganoderan and make, calculate with respect to the yield of medical material according to extract, and its parts by weight are:
50～1250 parts of baicalins, 7.5～360 parts of ganoderans, 30～1800 parts of Radix Salviae Miltiorrhizae total phenolic acidss; Be preferably: 125～500 parts of baicalins, 15～180 parts of ganoderans, 100～900 parts of Radix Salviae Miltiorrhizae total phenolic acidss; The best is: 250 parts of baicalins, 30～150 parts of ganoderans, 150～450 parts of Radix Salviae Miltiorrhizae total phenolic acidss.
In the aforementioned pharmaceutical compositions, the content of ganoderan is preferably and is not less than 30%, preferably is not less than 50%; The content of Radix Salviae Miltiorrhizae total phenolic acids is preferably and is not less than 30%, preferably is not less than 50%, and wherein the content of salvianolic acid B is preferably and is not less than 0.3%, preferably is not less than 1.5%.Ganoderan and Radix Salviae Miltiorrhizae total phenolic acids can make through above-mentioned technology.
More than form to be by weight as proportioning; When producing, can or reduce according to the corresponding proportion increase; Like large-scale production can be unit with the kilogram, or is unit with the ton, and small-scale production can be unit with the gram also; Weight can increase or reduce, but the constant rate of weight proportion between each composition.
The ratio of above weight proportion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
The consumption of drug component of the present invention is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.
The invention provides a kind of medicine that is used to have good hepatoprotective effect, can be used for various acute, chronic hepatitis.
Pharmaceutical composition of the present invention can add one or more pharmaceutically acceptable carriers, with oral, snuffing is gone into or the mode of parenteral is applied to the patient who needs this treatment.Be used for when oral; Can be made into conventional solid preparation; Like tablet, capsule, soft capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, process liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, like liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.The preferred dosage form of this compositions is injection or oral formulations.
Pharmaceutical composition of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises the conventional diluent of pharmaceutical field, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant etc.
Pharmaceutical composition of the present invention in order to increase its dissolubility, can add solubilizing agents such as Tween-80 when processing injection.Can add the isoosmotic adjusting agent that is used to regulate osmotic pressure in the transfusion, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.
Compositions of the present invention has the following advantages:
(1) the invention provides a kind of new pharmaceutical composition that is used to treat hepatitis, satisfied clinical needs.
(2) first through pharmacodynamic experiment research proof: the chmice acute hepatic injury due to pharmaceutical composition Abensanil of the present invention, the carbon tetrachloride has significant protective effect; The breeding of dhbv dna can be significantly suppressed, the rat liver fibrosis due to the carbon tetrachloride can be significantly resisted.Three medical instruments have synergistic function, and are evident in efficacy, produced beyond thought effect.
(3) each proportioning of pharmaceutical composition of the present invention is carried out pharmacodynamic study, drawn the optimal proportion of the present composition.
(5) crude drug among the present invention is except that baicalin, and Ganoderma, Radix Salviae Miltiorrhizae can directly feed intake with medical material or extract, and preparation technology is simple, can make between the different batches medicine mass discrepancy little, and drug quality is more uniform and stable.
(5) confirm drug combination injection safety and stability of the present invention through test of specific safety property and stability experiment.
(6) baicalin has good antihepatitic activity, and Ganoderma and Radix Salviae Miltiorrhizae are made adjuvant can significantly improve antihepatitic activity, and the drug combination determined curative effect is with a wide range of applications.
Below come further to set forth the beneficial effect of medicine according to the invention through experimental example.The compositions of baicalin, Ganoderma and Radix Salviae Miltiorrhizae hereinafter to be referred as
The HLD compositionsUsed ganoderan is taken from embodiment 1 in the experimental example, and Radix Salviae Miltiorrhizae total phenolic acids is taken from embodiment 2.
Experimental example 1 HLD compositions drug combination drug efficacy study
Test sample: 0.9% normal saline, self-control;
Baicalin for injection liquid, self-control, 2ml:250mg;
The Ganoderma injection, self-control, 2ml contains ganoderan 97.2mg (being equivalent to Ganoderma 6g);
Radix Salviae Miltiorrhizae Injection, self-control, 5ml contains Radix Salviae Miltiorrhizae total phenolic acids 300.0mg (being equivalent to Radix Salviae Miltiorrhizae 15g);
The different proportionings of HLD composite injection (baicalin+Ganoderma+Radix Salviae Miltiorrhizae), self-control, method for preparing is with reference to embodiment 3.
Laboratory animal: ICR mice, body weight 18～25g, male and female half and half.
Experimental technique: get 140 of mices, be divided into 14 groups at random, 10 every group, group sees the following form.Blank group and model group tail vein injection saline every day 20ml/kg Mus are heavy, every day 1 time, 10d continuously; The administration of administration group tail vein injection, every day 1 time, dosage sees the following form, continuously 10d.The blank group is tail vein injection 6h pneumoretroperitoneum injecting normal saline the last time.Model group and administration group tail vein injection 6h pneumoretroperitoneum injection with acetaminophen 300mg/kg Mus the last time are heavy; Each group breaks end behind intraperitoneal injection of saline and acetaminophen 16h; Get blood, liver; Carry out the test of biochemical indicator Serum ALT (glutamate pyruvate transaminase) and hepatic tissue LPO (lipid peroxide), the result sees table 1.
The influence of table 1HLD compositions Abensanil injured mice hepatic tissue ALT and LPO
Compare with the blank group,
◇ ◇P＜0.01; Compare with model group,
*P＜0.05,
*P＜0.01; Compare with the baicalin group,
#P＜0.05,
##P＜0.01; Compare with the Ganoderma group,
△P＜0.05,
△ △P＜0.01; Compare with the Radix Salviae Miltiorrhizae group,
☆P＜0.05,
☆ ☆P＜0.01.
Conclusion: compare with the blank group, the active of model group ALT and LPO significantly raises, and difference is (P＜0.01) extremely significantly, explains that modeling is reliable.Compare with model group, active obviously reduce (P＜0.05, P＜0.01) of baicalin group, Ganoderma group, Radix Salviae Miltiorrhizae group and each proportioning group ALT of HLD compositions and LPO explains that the hepatic injury of the equal Abensanil induced mice of each medicine has protective effect.Wherein each proportioning group better efficacy (P＜0.01) of HLD compositions all is superior to list with baicalin, Ganoderma and Radix Salviae Miltiorrhizae, explains that baicalin, Ganoderma and Radix Salviae Miltiorrhizae three medicines share, and have synergistic function.In each proportioning group of HLD compositions, all remarkable with baicalin+Ganoderma+Radix Salviae Miltiorrhizae (250mg+6g+15g) group curative effect.
Experimental example 2 HLD compositionss are to carbon tetrachloride (CCl
4
) cause the protective effect of chmice acute hepatic injury
Test sample: 0.9% normal saline, self-control;
Baicalin for injection liquid, self-control, 2ml:250mg;
HLD composite injection (baicalin+Ganoderma+Radix Salviae Miltiorrhizae 250mg+6g+15g), self-control, method for preparing is with reference to embodiment 3.
Laboratory animal: ICR mice, body weight 22～26g, male and female half and half.
Experimental technique: get 60 of mices, be divided into 6 groups at random, be respectively blank group, model group, baicalin group, the basic, normal, high dose groups of HLD composite injection, 10 every group.Blank group and model group tail vein injection saline every day 20ml/kg Mus are heavy, every day 1 time, 7d continuously; The administration of administration group tail vein injection, every day 1 time, dosage sees the following form, continuously 7d.The blank group is tail vein injection 2h pneumoretroperitoneum injection Oleum Arachidis hypogaeae semen 10ml/kg the last time, the equal lumbar injection 0.12%CCl of all the other each treated animals
4Peanut oil solution 10ml/kg.Sacrificed by decapitation animal behind the 16h, the value of getting serologic test ALT, AST.After broken end is got blood, cut open the belly immediately and take out liver, spleen, inhale the liquid of dehematizing, cut off fat, mesentery, the weight of the liver of accurately weighing, spleen is calculated liver exponential sum spleen index.The result sees table 2.
Table 2HLD compositions is to CCl
4Due to the influence of acute liver damage Mouse Liver, spleen index and Serum ALT, AST content
Compare with the blank group
◇P＜0.05,
◇ ◇P＜0.01; Compare with model group,
*P＜0.05,
*P＜0.01; Compare with the baicalin group,
#P＜0.05,
##P＜0.01
Conclusion: CCl
4Model group Mouse Liver index, the normal control group mice numerical value of spleen index significantly increase (P＜0.05), CCl
4Model group mice serum ALT, the normal control group mice numerical value of AST value extremely significantly increase (P＜0.01), and injected in mice CCl is described
4Hepar damnification behind the peanut oil solution, the modeling success, model stability is reliable.Compare with model group, each dose groups Mouse Liver index of HLD compositions, spleen index significantly reduce (P＜0.05), and liver, splenomegaly alleviate, and each dose groups Serum ALT of HLD compositions, AST value obviously reduce (P＜0.01), explain that the present composition is to CCl
4Due to acute liver damage protective effect is arranged.Each dose groups curative effect of HLD compositions all is superior to list and uses baicalin, explains that baicalin, Ganoderma and Radix Salviae Miltiorrhizae three medicines share, and synergistic function is arranged, wherein middle and high dose groups better efficacy (P＜0.05 or P＜0.01).
The anti-dhbv dna effect of experimental example 3HLD compositions
Test sample: 0.9% normal saline, self-control;
The injection acyclovir, Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd., Shiyao Group;
Baicalin for injection liquid, self-control, 2ml:250mg;
HLD composite injection (baicalin+Ganoderma+Radix Salviae Miltiorrhizae 250mg+6g+15g), self-control, method for preparing is with reference to embodiment 3.
Laboratory animal: commercially available 1 age in days Beijing duck;
DHBV (DHB) positive serum, microbiology teaching and research room of Medical Center of Fudan University.
Experimental technique:
The animal model Beijing duck is got blood through sufficient intravenous injection 0.2mlDHBV positive serum behind the 7d, separation of serum, and-20 ℃ of preservations are to be checked.
Drug therapy filters out 36 of the positive ducks that infect successfully, is divided into 6 groups at random, 6 every group, is respectively blank group, baicalin group, positive controls, the basic, normal, high dose groups of HLD composite injection, 6 every group.The blank group is irritated stomach normal saline 20ml/kg every day, every day 2 times, 14d continuously; Administration group gastric infusion, every day 2 times, dosage sees the following form, continuously 14d.Positive drug is pressed 100mg/kg with acyclovir (ACV) and is irritated stomach, 2 times/d, 2 weeks of administration as the treatment matched group.Be respectively applied for (1d), the 7th day (T of medication before the medicine
7), the 14th day (T of medication
14) and drug withdrawal after the 7th day (P
7).Get blood from duck lower limb shin vein, separation of serum ,-20 ℃ of preservations are to be checked.Adopt DHBV-DNA DotBlot method, with hybridization spot absorbance (A) as BIAO and BEN DHBV-DNA level value.The result sees table 3.
Table 3HLD compositions is to the inhibitory action of DHBV-DNA
Annotate: compare with the blank group
◇P＜0.05,
◇ ◇P＜0.01; With compare before the administration
P＜0.05,
P＜0.01.
Conclusion: positive control (acyclovir) group after administration the 7th day and the 14th day, with before the administration and with the blank group relatively, difference has utmost point significance (P＜0.01), but significantly rising again after the drug withdrawal does not have significance (P＞0.05) with comparing difference before the administration.Various dose HLD compositions all has inhibitory action to DHBV, and does not have knock-on after the drug withdrawal, and wherein middle and high dose groups inhibitory action is more obvious.Each administration group curative effect of HLD compositions all is superior to list and uses baicalin, explains that baicalin, Ganoderma and Radix Salviae Miltiorrhizae three medicines share, and have synergistic function.
The Hepar Mus fibrosis effect of the experimental example 4HLD compositions Chinese People's Anti-Japanese Military and Political College
Test sample: 0.9% normal saline, self-control;
Baicalin for injection liquid, self-control, 2ml:250mg;
HLD composite injection (baicalin+Ganoderma+Radix Salviae Miltiorrhizae 250mg+6g+15g), self-control, method for preparing is with reference to embodiment 3.
Laboratory animal: the Wistar rat, body weight 180～230g, male.
Experimental technique: get 10 of healthy rats, subcutaneous injection Oleum Arachidis hypogaeae semen 3ml/kg, every day 1 time, totally 10 weeks are as matched group.The Liver Fibrosis Model group is used 40%CCl
4Peanut oil solution is pressed the 3ml/kg subcutaneous injection, 2 times weekly, in totally 8 weeks, induces Liver Fibrosis Model.Get 50 of Liver Fibrosis Model rats, be divided into 5 groups at random, be respectively model group, baicalin group, the basic, normal, high dose groups of HLD composite injection, 10 every group.Except that matched group, all the other each groups continue with 40%CCl
4Peanut oil solution 3ml/kg subcutaneous injection, every day 1 time.Baicalin group, the basic, normal, high dose groups of HLD composite injection be the gastric infusion relative medicine simultaneously, and dosage sees the following form.Continue 2 weeks of administration.Slaughter rat after 10 weeks, blood 2ml gets in the sterile working, separation of serum, and-20 ℃ of preservations detect hepatic fibrosis index with radioimmunology: hyaluronic acid (HA) and laminin (LN); Detect glutamate pyruvate transaminase (ALT) and glutamic oxaloacetic transaminase, GOT (AST) with biochemical process, adopt automatic clinical chemistry analyzer to detect.The result sees table 4.
Conclusion: compare with the blank group, model group rat blood serum ALT, AST, HA, LN content have significant difference, explain that model stability is reliable.Baicalin, HLD combination treatment heptic fibrosis rat blood serum ALT and AST all are lower than model group, and difference has significance (P＜0.05 or P＜0.01), and prompting baicalin, HLD compositions have the effect of falling enzyme and liver function protecting; Serum HA and LN level all significantly are lower than model group behind baicalin, the HLD combination treatment, and difference has significance (P＜0.05 or P＜0.01), and prompting baicalin, HLD compositions all can be improved the hepatic fibrosis serological index, have the effect of anti-hepatic fibrosis.Wherein, HLD compositions group curative effect is superior to the baicalin group, and prompting baicalin, Ganoderma and Radix Salviae Miltiorrhizae three medicines share, and synergistic function is arranged.
Table 4HLD compositions is to CCl
4Due to the influence of serological index of hepatic fibrosis rats
Compare with the blank group
◇ ◇ ◇P＜0.001; Compare with model group,
*P＜0.05,
*P＜0.01; Compare with the baicalin group,
#P＜0.05.
Experimental example 5 injected in mice administration acute toxicity testings
(1) experimental technique
Test sample: the HLD composite injection, dosage form: liquid drugs injection, specification: 10ml derives from embodiment 3;
Animal subject: mice, each 5 of every group of male and female, male body weight 25～28g, female body weight 21～24g.
Route of administration: intravenous injection, lumbar injection.
Observation item: death toll, general state, body weight, cut open inspection, half lethal dose.
(2) experimental result
Require to carry out prerun according to acute toxicity testing, lumbar injection and intravenous injection two route of administration all can't be measured the median lethal dose(LD 50) of medicine, also do not see tangible toxic reaction, so carry out maximum dosage-feeding experiment in a day.Dosage: tail vein injection HLD composite injection 0.2ml/10g, lumbar injection HLD composite injection 0.2ml/10g, 2 times on the one.
Death toll: do not occur dead.
General state: no abnormality seen changes.
Body weight: in administration preceding 1 day, administration day, measured in 1,3,7,14 day after the administration; No abnormality seen changes.
Cut open inspection: the heart, liver, lung, kidney etc. organize no abnormality seen to change.
(3) conclusion
Occur death in this experiment, infer that the HLD composite injection is 0.4ml/10g to the maximum tolerated dose of male and female mouse vein and intraperitoneal injection, be equivalent to 100 times of maximum consumption 20ml of the 50kg body weight day for human beings.Show these article low toxicity, safe.
Experimental example 6 HLD composite injection stability experiments
Test sample: the HLD composite injection, dosage form: liquid drugs injection, specification: 10ml derives from embodiment 3;
Investigation project: character, pH value, clarity.
Long-time stability experimental technique and result: the condition held 6 months, 12 months of these article composite injection being put 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%; Each item index has no significant change, and experimental result shows that the long-term placement of HLD composite injection is basicly stable.
4, the specific embodiment
Below, foregoing of the present invention is done further to specify through the specific embodiment of embodiment form.But should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.Embodiment 3～12 used ganoderans are taken from embodiment 1, and Radix Salviae Miltiorrhizae total phenolic acids is taken from embodiment 2.
The preparation of embodiment 1 ganoderan
Get the Ganoderma medical material, be ground into coarse grain, add the moistening of 3 times of amounts of water and spend the night, decoct next day three times, added 12 times of amounts of water for the first time in 3 hours, added 10 times of amounts of water for the second time in 2 hours; Added 10 times of amounts of water in 1 hour for the third time, collecting decoction filters, and it is 1.02～1.06 that filtrating is concentrated into relative density, puts coldly, adds ethanol and makes that to contain the alcohol amount be 65%; Stir, placed 24 hours at 4 ℃, filter, filtrate recycling ethanol filters to there not being the alcohol flavor; Add ethanol and make that to contain alcohol amount be 80%, stir, placed 24 hours at 4 ℃, filter, filtrate recycling ethanol is to there not being the alcohol flavor; Placed 48 hours at 4 ℃, filter, filtrating is concentrated into the thick paste shape, and spray drying promptly gets.
Prepare three batches of extracts respectively, extract yield and content see the following form 5.
Differentiate
These article of getting 50mg adds ethanol 25ml, and reflux 30 minutes filters, the filtrating evaporate to dryness, and residue adds methanol 2ml makes dissolving, as need testing solution.Other gets Ganoderma control medicinal material 2g, shines medical material solution in pairs with legal system.According to the thin layer chromatography test, draw above-mentioned two kinds of each 5ul of solution, put respectively on same silica gel G plate; Upper solution with petroleum ether (60～90 ℃)-Ethyl formate-formic acid (15: 5: 1) is developing solvent, launches, and takes out; Dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
Assay
It is an amount of that the preparation precision of reference substance solution takes by weighing 105 ℃ of glucose reference substances that are dried to constant weight, adds water and process the solution that every 1ml contains 0.1mg, promptly gets.
The preparation of standard curve is quiet close absorption reference substance solution 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1.0ml, 1.2ml respectively, puts in the 10ml tool plug test tube, adds water to 2.0ml; Accurate sulphuric acid anthrone solution (the quiet close anthrone 0.1g that takes by weighing adds 80% sulfuric acid solution 100ml and makes dissolving, the shakes up) 6ml that adds; Shake up, put in the water-bath and heated 15 minutes, take out; Putting into water-bath cooling 15 minutes, is blank with the corresponding solvent, under 625nm, measures absorbance; With the absorbance is vertical coordinate, and concentration is abscissa, the drawing standard curve.
These article 20mg is got in the preparation of need testing solution, puts in the 50ml measuring bottle, is dissolved in water, and is diluted to scale, shakes up promptly to get.
The accurate need testing solution 2ml that draws of algoscopy puts in the 10ml tool plug test tube, and assay method under the sighting target directrix curve is measured absorbance in accordance with the law, from the weight that standard curve is read the glucose of need testing solution, calculates, and promptly gets.
According to above-mentioned technology, make ganoderan three lot sample article, its yield and content see the following form.Can be found out that by the result extract yield through ganoderan in the Radix Astragali extract of this prepared is 0.5～3%, content is not less than 50%.
Table 5 ganoderan yield and assay result
The preparation of embodiment 2 Radix Salviae Miltiorrhizae total phenolic acidss
Get Radix Salviae Miltiorrhizae, be ground into coarse grain, decocte with water three times, 2 hours for the first time, add 12 times of amounts of water, second and third time each 1.5 hours adds 10 times of amounts of water, and collecting decoction filters, and it is 1.17～1.20 (80 ℃) that filtrate decompression is concentrated into relative density.Add the ethanol precipitation secondary, make for the first time that to contain the alcohol amount be 75%, make that to contain the alcohol amount be 85% for the second time, respectively leave standstill 24h, reclaiming ethanol to relative density is 1.17～1.20 (80 ℃ of surveys), and spray drying promptly gets.
Differentiate
These article of getting 0.2g, porphyrize adds 70% methanol 25ml, and reflux 1 hour filters, the filtrating evaporate to dryness, residue adds 70% methanol 1ml makes dissolving, as need testing solution.Other gets the salvianolic acid B reference substance, adds 70% methanol and processes the solution that every 1ml contains 2mg, as reference substance solution.Use tlc determination, draw above-mentioned two kinds of each 5ul of solution, put in same silica gel G F respectively
254On the lamellae, be developing solvent, launch, take out, dry, put under the ultra-violet lamp (254nm) and inspect with toluene-chloroform-ethyl acetate-methanol-formic acid (2: 3: 4: 0.5: 2).
In the test sample chromatograph, with reference substance chromatograph relevant position on, show the speckle of same color.
Assay
Total phenolic content is measured colorimetry
The preparation precision of reference substance solution takes by weighing the protocatechualdehyde reference substance 1mg that is dried to constant weight in 105 ℃, is dissolved in water, and is settled to 100ml.The preparation precision of need testing solution takes by weighing sample 50mg, puts in the 50ml volumetric flask, and thin up to scale precision is measured 0.1ml and put and add ethanol 5ml in the 25ml volumetric flask; Add 0.3% sodium lauryl sulphate 2ml, 0.6% potassium ferricyanide-0.9% ferric oxide (face and use preceding mixed in equal amounts) 1ml, so 5min is placed in the dark place; Add the 0.1mol/L hydrochloric acid solution to scale, shake up, after 20min is placed in the dark place; Put in the lena colorimetric pool, the 720nm place measures.
The assay HPLC of salvianolic acid B
Chromatographic condition and system suitability experiment are filler with the octadecylsilane chemically bonded silica; With methanol-acetonitrile-formic acid-water (30: 10: 1: 59) be mobile phase; The detection wavelength is 286nm.Theoretical cam curve is calculated by the danshensu peak should be not less than 1500.
It is an amount of that the preparation precision of reference substance solution takes by weighing the salvianolic acid B reference substance, adds 75% methanol and process the solution that every 1ml contains 0.14mg, promptly gets.
The about 0.2g of these article is got in the preparation of need testing solution, and accurate the title decides, and puts in the tool plug conical flask, and the accurate 75% methanol 50ml that adds claims to decide weight; Reflux 1h takes out, and puts coldly, claims to decide weight again, supplies with 75% methanol to subtract weight loss; Shake up, filter, get subsequent filtrate, promptly get.
Accurate respectively reference substance solution and each 20ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, and promptly gets.
According to above-mentioned technology, make Radix Salviae Miltiorrhizae total phenolic acids three lot sample article, its content and yield see the following form 6.Can be found out that by the result Radix Salviae Miltiorrhizae total phenolic acids yield through this prepared is 1～3%, the content of Radix Salviae Miltiorrhizae total phenolic acids is not less than 50%, and the content of salvianolic acid B is not less than 1.5%.
The content of table 6 Radix Salviae Miltiorrhizae total phenolic acids yield and Radix Salviae Miltiorrhizae total phenolic acids and salvianolic acid B
The preparation of embodiment 3 HLD compositions aqueous injection
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Polyoxyethylene sorbitan monoleate 50g
Water for injection adds to 1000ml
Prepare 1000 altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) ganoderan is added in the water for injection of dosing amount 30% the heated and stirred dissolving fully.Radix Salviae Miltiorrhizae total phenolic acids and baicalin are added a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) with the solution sealing by fusing in glass ampule.
9) 100 ℃ of flowing steam sterilizations are 30 minutes.
10) while hot sample being put into 0.01% methylene blue solution hunts leak.
11) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 4 HLD composition powder injections
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Polyoxyethylene sorbitan monoleate 20g
Mannitol 400g
Sterile water for injection adds to 5000ml
Prepare 1000 altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
1) vessel and the antibiotic glass bottle at first dosing used, plug etc. carry out aseptic process.
2) take by weighing supplementary material according to recipe quantity.
3) ganoderan is added in the water for injection of dosing amount 30% the heated and stirred dissolving fully.Radix Salviae Miltiorrhizae total phenolic acids and baicalin are added a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, add sterile water for injection to full dose.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.22um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.Pre-freeze-45 ℃ 5 hours, low-temperature vacuum drying-45 ℃～0 ℃ 20 hours was warming up to 25 ℃ of vacuum dryings 3 hours then.
9) lyophilizing finishes, and lid is rolled in tamponade.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 5 HLD compositions sodium chloride transfusion
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Polyoxyethylene sorbitan monoleate 20g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
1) handles the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) ganoderan is added in the water for injection of dosing amount 30% the heated and stirred dissolving fully.Radix Salviae Miltiorrhizae total phenolic acids and baicalin are added a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.With sodium chloride with an amount of water for injection dissolving fully, merge above-mentioned solution, benefit adds to the full amount of water for injection.
3) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
4) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
5) through the microporous filter membrane fine straining of 0.45um.
6) clarity of inspection solution, the semi-finished product chemical examination.
7) fill is in the infusion bottle of 100ml.
8) 115 ℃ of pressure sterilizings are 30 minutes.
9) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 6 HLD compositions glucose infusion liquids
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Polyoxyethylene sorbitan monoleate 20g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) ganoderan is added in the water for injection of dosing amount 30% the heated and stirred dissolving fully.Radix Salviae Miltiorrhizae total phenolic acids and baicalin are added a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, benefit adds to the full amount of water for injection.Glucose is complete with the water for injection dissolving of dosing amount 40%, heated and boiled 15 minutes.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 7 HLD composition tablets
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Starch 40g
Microcrystalline Cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 5.0g
Carboxymethylstach sodium 10.0g
Prepare 2000 altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
1) it is subsequent use ganoderan, baicalin and Radix Salviae Miltiorrhizae total phenolic acids pulverize separately to be crossed 100 mesh sieves.
2) take by weighing supplementary material according to recipe quantity.
3) hypromellose 2% the aqueous solution processed soluble in water is subsequent use.
4) with baicalin, Radix Salviae Miltiorrhizae total phenolic acids, ganoderan, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and processes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) the sheet weight sheet of confirming according to chemical examination.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 8 HLD composition capsules
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Starch 20.0g
Microcrystalline Cellulose 60.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 5.0g
Prepare 2000 altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
1) it is subsequent use ganoderan, baicalin and Radix Salviae Miltiorrhizae total phenolic acids pulverize separately to be crossed 100 mesh sieves.
2) take by weighing supplementary material according to recipe quantity.
3) hypromellose 2% the aqueous solution processed soluble in water is subsequent use.
4) with baicalin, Radix Salviae Miltiorrhizae total phenolic acids, ganoderan, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and processes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) loading amount of confirming according to chemical examination incapsulates.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 9 HLD composition granules
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Icing Sugar 500.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
1) it is subsequent use sucrose to be pulverized 100 mesh sieves.It is subsequent use that ganoderan, baicalin and Radix Salviae Miltiorrhizae total phenolic acids pulverize separately are crossed 100 mesh sieves.
2) take by weighing supplementary material according to recipe quantity.
3) the method mix homogeneously that ganoderan, baicalin, Radix Salviae Miltiorrhizae total phenolic acids and Icing Sugar is progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and processes suitable soft material,
4) cross 20 mesh sieve system granules.
5) granule is dried under 60 ℃ condition.
6) dried granule is crossed 18 mesh sieve granulate.
7) sampling, the content of principal agent is confirmed loading amount in the semi-finished product chemical examination granule.
8) packing, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 10 HLD composition dripping agent
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Polyethylene glycol 6000 1000g
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
Pulverized behind 100 mesh sieves ganoderan, baicalin and Radix Salviae Miltiorrhizae total phenolic acids subsequent use.With polyethylene glycol 6000 heating and melting in water-bath, treat to add ganoderan, baicalin and Radix Salviae Miltiorrhizae total phenolic acids after whole fusions, stirring and dissolving, 60 mesh sieves filter, and keep 60 ℃ to splash in the liquid paraffin that is chilled to below 10 ℃ and process ball.
The preparation of embodiment 11 HLD composition soft agent
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Soybean oil 300.0g
Soybean phospholipid 40g
Cera Flava 40g
Prepare 2000 altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
With the soybean oil of recipe quantity and soybean phospholipid, Cera Flava heating and melting, mixing is put coldly, adds baicalin, Radix Salviae Miltiorrhizae total phenolic acids, ganoderan and grinds well, and is pressed into soft capsule and gets final product.
The preparation of embodiment 12 HLD composition oral liquid agent
Prescription:
Baicalin 250.0g
Ganoderan 97.2g (being equivalent to Ganoderma 6kg)
Radix Salviae Miltiorrhizae total phenolic acids 300.0g (being equivalent to Radix Salviae Miltiorrhizae 15kg)
Polyoxyethylene sorbitan monoleate 20g
Sodium benzoate 15g
Stevioside 20g
Purified water adds to 10000ml
Prepare 1000 altogether
Annotate: main effective ingredient total content is 61.9% in the Chinese medicine total extract.
Preparation technology:
1) ganoderan is added in the water of dosing amount 30% the heated and stirred dissolving fully.Radix Salviae Miltiorrhizae total phenolic acids and baicalin are added low amounts of water, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, add purified water to full dose.
2) sodium benzoate and stevioside is complete with the water dissolution of dosing amount 20%.
3) merge above-mentioned two solution, mend and add water to full dose.
4) filtering with microporous membrane of mistake 0.8um.
5) semi-finished product chemical examination.
6) fill.Finished product is examined entirely, the packing warehouse-in.
Claims (9)
1. pharmaceutical composition that is used to treat hepatitis; It is characterized in that said composition mainly processed by following bulk drugs: 50～1250 parts of baicalins, 500～24000 parts of Ganodermas, 1000～90000 parts of Radix Salviae Miltiorrhizaes; Ganoderma wherein and Radix Salviae Miltiorrhizae prepare extract with The suitable solvent and method; Main effective ingredient contained in the extract is: ganoderan and Radix Salviae Miltiorrhizae total phenolic acids, and wherein the content of ganoderan is not less than 30%; The content of Radix Salviae Miltiorrhizae total phenolic acids is not less than 30%, and wherein the content of salvianolic acid B is not less than 0.3%.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the parts by weight of each crude drug are: 125～500 parts of baicalins, 8000～32000 parts of Ganodermas, 5000～45000 parts of Radix Salviae Miltiorrhizaes.
3. pharmaceutical composition as claimed in claim 2 is characterized in that the parts by weight of each crude drug are: 250 parts of baicalins, 6000 parts of Ganodermas, 15000 parts of Radix Salviae Miltiorrhizaes.
4. like the described arbitrary preparation of drug combination method of claim 1-3; It is characterized in that; Ganoderma wherein and Radix Salviae Miltiorrhizae prepare extract with The suitable solvent and method; Total extract is processed arbitrary preparation with baicalin and mixing acceptable accessories again, and main effective ingredient contained in the total extract is: ganoderan and Radix Salviae Miltiorrhizae total phenolic acids.
5. preparation of drug combination method as claimed in claim 4 is characterized in that the total content of the main effective ingredient in the total extract is not less than 30%.
6. pharmaceutical composition that is used to treat hepatitis; It is characterized in that said composition mainly processed by following bulk drugs: baicalin, ganoderan and Radix Salviae Miltiorrhizae total phenolic acids, its weight proportion is: 50～1250 parts of baicalins, 7.5～360 parts of ganoderans, 30～1800 parts of Radix Salviae Miltiorrhizae total phenolic acidss.
7. pharmaceutical composition as claimed in claim 6, the weight proportion of its crude drug is: 125～500 parts of baicalins, 15～180 parts of ganoderans, 100～900 parts of Radix Salviae Miltiorrhizae total phenolic acidss.
8. pharmaceutical composition as claimed in claim 7, the weight proportion of its crude drug is: 250 parts of baicalins, 30～150 parts of ganoderans, 150～450 parts of Radix Salviae Miltiorrhizae total phenolic acidss.
9. like claim 1-3, the described arbitrary pharmaceutical composition of 6-8, it is characterized in that said composition and mixing acceptable accessories process clinically any or pharmaceutically acceptable dosage form.
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| CN2005100454113A CN1977888B (en) | 2005-12-05 | 2005-12-05 | Medicinal composition of baicalin, ganoderma lucidum and salvia miltrorrhiza |
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