CN101062047B - Combination including isoglycyrrhizinate and oxymatrine and the purpose thereof - Google Patents
Combination including isoglycyrrhizinate and oxymatrine and the purpose thereof Download PDFInfo
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- CN101062047B CN101062047B CN2006100400495A CN200610040049A CN101062047B CN 101062047 B CN101062047 B CN 101062047B CN 2006100400495 A CN2006100400495 A CN 2006100400495A CN 200610040049 A CN200610040049 A CN 200610040049A CN 101062047 B CN101062047 B CN 101062047B
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Abstract
The invention provides a medicinal composition which comprises kurarinone or its derivatives and isoglycyrrhizinic acid or its derivatives. The invention also provides the use of the pharmaceutical composition in treating acute and chronic hepatitis and related diseases. the invention also provides various dosage forms of the pharmaceutical composition.
Description
Technical field
The invention belongs to field of medicaments.Relate to a kind of medical composition and its use.Described pharmaceutical composition contains Isoglycyrrhiza acid and kurarinone or the derivant of the two.And this pharmaceutical composition the prevention and the treatment human hepatitis or with hepatitis relevant disease or tumor in purposes.
Background technology
Hepatic disease especially viral hepatitis is a kind of commonly encountered diseases and frequently-occurring disease in China.Still it there is not the medicine of ideal treatment at present.The clinical antiviral treatment that adopts, and auxiliary adding with hepatic to improve curative effect more.But because this type of medication effect is imprecise and very strong clinical side effects is arranged, often prognosis is undesirable.
Glycyrrhizic acid and kurarinone all have certain hepatitis virus resisting and hepatoprotective effect, and clinical had both like products to be used for the treatment of chronic hepatitis.But serious adverse reactions such as having water-sodium retention, hypertension and hypokalemia is taken in the steroid sample effect of glycyrrhizic acid for a long time, and oral administration easily forms micelle and causes the malabsorption bioavailability not high in intestinal.Kurarinone quasi drugs clinical efficacy is not good, and is used for the treatment of for a long time in the hepatitis B process, and the GI irritation effect is arranged.There is clinical report diammonium glycyrrhizinate capsule and Matrine Injection use in conjunction treatment chronic hepatitis B to obtain good curative effect, it is excessive that but the not thorough solution glycyrrhizic acid of this method oral formulations absorbs bad side effect, and the excessive patient of drug combination dosage takes inconvenient problem.
Summary of the invention
The present application people is surprised to find by a large amount of experimentatioies, and a kind of brand-new medicinal composition can provide useful especially hepatitis virus resisting, protects the liver, the effect of transaminase lowering.This Chinese medicine composition is made up of Isoglycyrrhiza acid or derivatives thereof and kurarinone or derivatives thereof.Compared with prior art replace glycyrrhizic acid, can alleviate the water-sodium retention of glycyrrhizic acid with Isoglycyrrhiza acid, untoward reaction such as hypokalemia, unexpectedly its therapeutic effect also significantly is better than the compositions of glycyrrhizic acid and kurarinone when alleviating drug side effect.
The purpose of this invention is to provide a kind of Isoglycyrrhiza acid or derivatives thereof and pharmaceutical composition of forming of kurarinone or derivatives thereof and an amount of acceptable accessories or carrier by dose therapeutically effective.This pharmaceutical composition can be used to the prevention and the treatment human hepatitis or with hepatitis relevant disease or tumor.The content of Isoglycyrrhiza acid or derivatives thereof is that the content of 30mg-3000mg, kurarinone or derivatives thereof is 20mg-2000mg in this pharmaceutical composition.Isoglycyrrhiza acid or derivatives thereof content is preferably 50mg-2000mg in this pharmaceutical composition, more preferably 100mg-1000mg; Kurarinone or derivatives thereof content is preferably 100mg-1500mg, more preferably 300mg-1000mg.This pharmaceutical composition can be by with Isoglycyrrhiza acid or derivatives thereof, the kurarinone or derivatives thereof of above-mentioned content range and after an amount of pharmaceutically acceptable carrier mixes, and is prepared according to the preparation method of the pharmaceutical preparation of routine.The mass ratio of Isoglycyrrhiza acid or derivatives thereof and kurarinone or derivatives thereof is in this pharmaceutical composition: 1: 10-10: 1, and preferred mass ratio is: 1: 5-5: 1.
Can be prepared into the dosage form that is fit to oral administration and drug administration by injection with aforementioned pharmaceutical compositions by described quality proportioning and add corresponding auxiliary material, also can be prepared into other dosage form, for example be fit to the dosage form etc. that percutaneous dosing or through mucous membrane absorb administration.
The pharmaceutical preparation that is fit to oral administration is meant that pharmaceutically the regular dosage form of oral administration comprises tablet, powder, granule, capsule, drop pill, oral liquid, pellet etc.Be preferably tablet, capsule, drop pill.Wherein tablet comprises plain sheet, coated tablet, slow releasing tablet, dispersible tablet, enteric coatel tablets, buccal tablet, chewable tablet, effervescent tablet etc.; Capsule comprises hard capsule, soft capsule, slow releasing capsule, enteric coated capsule etc.; Pellet comprises common pellets, slow-release micro-pill, enteric coated micropill, controlled release micro pill etc.
Pharmaceutically conventional excipient such as binding agent contained in the oral formulations comprises hypromellose, dextrin, Polyethylene Glycol, syrup, arabic gum, sorbitol, gelatin or polyvinylpyrrolidone etc.; Filler comprises lactose, corn starch, calcium phosphate, sorbitol or glycine etc.; The tabletting lubricant comprises magnesium stearate, Polyethylene Glycol etc.; Disintegrating agent comprises starch, polyvinylpyrrolidone, Explotab or microcrystalline Cellulose; Or pharmaceutically acceptable wetting agent comprises sodium lauryl sulphate etc.; Correctives and sweeting agent comprise stevioside, aspartame, steviosin, xylitol, menthol, flavoring orange essence etc.Preparation method adopts the preparation method of this area routine.
The preparation that is fit to drug administration by injection comprises dosage forms such as the injection of big or low capacity, aseptic powder packing.Wherein be preferably the vein injection of big or low capacity.
The preparation of drug administration by injection can utilize two kinds of active component and sterile carrier to be prepared from, and according to required concentration it is dissolved in the carrier.When preparation solution, active component can be dissolved in water for injection and filtration sterilization, be filled into sealing preservation in the container afterwards.Advantageously, can add injection adjuvant such as antiseptic commonly used, buffer agent, acidity-basicity regulator, Osmolyte regulator, solubilizing agent, stabilizing agent, antioxidant etc. in order to be fit to intravenous injection.
The alternate manner administration comprises externally used paste and suppository etc.
According to the difference of administering mode and preparation requirement, Isoglycyrrhiza acid or derivatives thereof and kurarinone or derivatives thereof content sum can be the 0.1%-99% of total content in the aforementioned pharmaceutical compositions, are preferably 1%-60%, more preferably 5%-30%.
The present invention provides a kind of simultaneously and is used to prevent and treats human hepatitis or the other diseases relevant with hepatitis or the administering drug combinations mode of tumor, and the dosage and the quality proportioning of administration.Described administering mode comprises the pharmaceutical preparation of the Isoglycyrrhiza acid or derivatives thereof that gives or give in proper order effective dose simultaneously and the pharmaceutical preparation of kurarinone or derivatives thereof.The dosage of described administration be the Isoglycyrrhiza acid or derivatives thereof pharmaceutical preparation for each person every day consumption be 30mg-3000mg, be preferably for each person every day that consumption is 50mg-2000mg, more preferably consumption 100mg-1000mg for each person every day.The pharmaceutical preparation of kurarinone or derivatives thereof consumption for each person every day is 20mg-2000mg, is preferably consumption 100mg-1500mg, more preferably 300mg-1000mg for each person every day; The quality proportioning of the pharmaceutical preparation of the pharmaceutical preparation of Isoglycyrrhiza acid or derivatives thereof and kurarinone or derivatives thereof is in the above-mentioned administering mode: 1: 10-10: 1, and preferred mass ratio is: 1: 5-5: 1.
" Isoglycyrrhiza acid " described in the present application content all refers to disclosed 18 alpha-liquorice acids of Chinese patent CN1381463A, i.e. 18 α, 20 beta-hydroxies-11-oxidation-positive oleanane-12-alkene-3 beta-yls-2-o-β-D-glucopyanosyl aldehydic acid base-α-D-Fructus Vitis viniferae pyrans glycosides aldehydic acid.The derivant of Isoglycyrrhiza acid is meant that pharmaceutically acceptable other forms of Isoglycyrrhiza acid comprise salt, ester and solvate etc.Wherein the salt of Isoglycyrrhiza acid comprises magnesium salt, ammonium salt, potassium salt, sodium salt, silver salt, calcium salt, iron salt, the zinc salt of Isoglycyrrhiza acid, preferred Isoglycyrrhiza acid potassium salt, magnesium salt, ammonium salt, most preferably Isoglycyrrhiza acid magnesium salt and ammonium salt; The ester of Isoglycyrrhiza acid mainly is meant the Arrcostab of Isoglycyrrhiza acid, for example methyl ester, ethyl ester, propyl ester, butyl ester, pentyl ester, preferably Isoglycyrrhiza acid methyl ester, ethyl ester; The solvate of Isoglycyrrhiza acid mainly comprises hydrate, ethanol compound of Isoglycyrrhiza acid etc." kurarinone " refers to oxymatrine described in the present application content.The derivant of kurarinone is meant that pharmaceutically acceptable other forms of oxymatrine comprise salt and solvate etc.Wherein the salt of oxymatrine comprises hydrochlorate, sulfate, acetate, fumarate and the various amino acid salts etc. of oxymatrine, is preferably the hydrochlorate and the fumarate of oxymatrine; Solvate mainly is meant hydrate, ethanol compound of oxymatrine etc.
The Isoglycyrrhiza acid or derivatives thereof of the pharmaceutically acceptable form of all that provide among the application and the labelled amount of kurarinone or derivatives thereof provide with respect to particular compound itself, and for example the Isoglycyrrhiza acid of 500mg magnesium salt form is meant the 500mg magnesium isoglycyrrhetate.Kurarinone is identical therewith.
The described human hepatitis of the application or with hepatitis relevant disease or tumor, be meant that viral hepatitis is meant hepatitis B especially.
" giving simultaneously " described in the application is meant simultaneously or gives substantially simultaneously Isoglycyrrhiza acid or derivatives thereof, kurarinone or derivatives thereof." order gives " is meant in chronological sequence and gives Isoglycyrrhiza acid or derivatives thereof, kurarinone or derivatives thereof according to clinical treatment.
The present inventor has investigated the compositions of described Isoglycyrrhiza acid or derivatives thereof and kurarinone or derivatives thereof to CCL
4, two kinds of liver injury model animal liver of BCG+LPS function influence and chmice acute toxicity test LD
50The inventor is surprised to find under same dose combination by Isoglycyrrhiza acid or derivatives thereof and kurarinone or derivatives thereof can significantly strengthen Isoglycyrrhiza acid, the kurarinone liver protection to chemical hepar damnification, immunologic liver injury; show that said composition can strengthen removing to the pathologic free radical, suppresses lipid peroxidation, protection liver plasma membrane and can regulate body's immunological function, have very strong protect the liver, fall enzyme, antiphlogistic effect.And said composition can significantly reduce the acute toxicity of compositions.By the analysis to experimental data, the inventor finds that the mass ratio when Isoglycyrrhiza acid and kurarinone is 1: 5-5: its function for protecting liver and reducing enzyme activity is the strongest in the time of 1, and when this quality proportioning mice LD
50Value is maximum, the toxic action minimum.The beneficial effect of Isoglycyrrhiza acid or derivatives thereof and kurarinone or derivatives thereof compositions describes in detail by the pharmacological experiment that embodiment 1,2,3 is put down in writing.
The specific embodiment
Below we specify the present invention in conjunction with the embodiments.Following examples only are used to technical scheme of the present invention is described, are not to be used to limit the present invention.
Embodiment 1 magnesium isoglycyrrhetate and kurarinone different proportion compositions are to CCL
4The protective effect of the mouse liver damage that causes
Laboratory animal: Kunming mouse, male.China Medicine University's Experimental Animal Center provides, the animal quality certification number: No. 200501002, Soviet Union's moving (matter)
Experiment medicine: kurarinone, magnesium isoglycyrrhetate.Provide lot number by the honest day research and development centre of fine Pharmacy stock Co., Ltd in Jiangsu Chinese medicine laboratory: 051002.Be made into the solution of different proportion concentration with normal saline according to requirement of experiment.
70 of 18-20g Kunming mouses, male, be divided into 7 groups at random by body weight: normal control group, model control group, 3 groups of different proportion kurarinones and Isoglycyrrhiza acid magnesium compositions group, kurarinone group, magnesium isoglycyrrhetate group.According to various dose with 0.25ml/10g volume gastric infusion, continuous 7 days.2h after the last administration, all the other respectively organize ip0.25%CCl except that the normal control group
4-olive oil 10ml/kg, fasting is freely drunk water, and 24h posterior orbit vein is got blood, and the centrifugal 15min separation of serum of 2500rpm is got determination of serum serum glutamic pyruvic transminase (ALT), glutamic oxaloacetic transaminase, GOT (AST).
Table 1. magnesium isoglycyrrhetate and kurarinone different proportion compositions are to CCL
4The influence of model mice liver function (X ± s, n=10)
Annotate: with the normal control group than #P＜0.05, ###P＜0.001; With the model control group ratio
*P＜0.05,
*P＜0.01,
* *P＜0.001; " hardship " expression kurarinone; " different sweet " expression magnesium isoglycyrrhetate.It between kurarinone and the magnesium isoglycyrrhetate mass ratio.
By experiment the result as can be known, the compositions of different proportion kurarinone and magnesium isoglycyrrhetate is to CCL among the present invention
4The mice chemical liver injury that causes has significant protective effect, significantly strengthens not strengthening under the drug dose situation the liver protecting and ALT lowering effect, has shown of the present invention substantive progressive.
The protective effect of the mouse immune hepar damnification that embodiment 2 magnesium isoglycyrrhetates and kurarinone different proportion compositions cause BCG+LPS.
Laboratory animal: Kunming mouse, male.China Medicine University's Experimental Animal Center provides, the animal quality certification number: No. 200501002, Soviet Union's moving (matter)
The experiment medicine: magnesium isoglycyrrhetate, kurarinone provide lot number by the honest day research and development centre of fine Pharmacy stock Co., Ltd in Jiangsu Chinese medicine laboratory: 051002.Be used for drug administration by injection according to requirement of experiment with the solution that normal saline is made into different proportion concentration.Bacillus calmette-guerin vaccine (BCG): Shanghai Vaccine and Serum Institute, lot number: 200504001.Lipopolysaccharide (LPS): U.S. Sigma company product.AST, ALT test kit: bio-engineering research institute, lot number: 20050905,20050828 are built up in Nanjing.
Each treated animal adaptability of modeling method was fed after 3 days, except that the normal control group, and 1 tail vein injection BCG 5 * 10 of every mice
7Individual viable bacteria, 1 tail vein injection LPS10 of the 7th day every mice μ g after injection of BCG, the normal control group is all injected the equivalent normal saline twice in the same way.
70 of 20 ± 2g Kunming mouses, male, be divided into 7 groups at random by body weight: normal control group, model control group, 3 groups of different proportion kurarinones and Isoglycyrrhiza acid magnesium compositions group, kurarinone group, magnesium isoglycyrrhetate group.Each treated animal began to irritate respectively stomach in second day and gives normal saline or be subjected to the reagent thing behind tail vein injection BCG, and after the last administration one hour, tail vein injection LPS.After the modeling, after the animal fasting was freely drunk water and spent the night 12 hours, eye socket was got blood, and the centrifugal 15min separation of serum of 2500rpm is measured serum glutamic pyruvic transminase (ALT), glutamic oxaloacetic transaminase, GOT (AST).
Table 2. magnesium isoglycyrrhetate and kurarinone different proportion compositions to the influence of BCG+LPS model mice liver function (X ± s, n=10)
Annotate: with the normal control group than #P＜0.05, ###P＜0.001; With the model control group ratio
*P＜0.05,
*P＜0.01,
* *P＜0.001; " hardship " expression kurarinone; " different sweet " expression magnesium isoglycyrrhetate.It between kurarinone and the magnesium isoglycyrrhetate mass ratio.
By this experiment as can be known; the filling stomach gives the compositions of the kurarinone and the magnesium isoglycyrrhetate of different proportion; can effectively protect the mouse immune hepar damnification that causes by BCG+LPS, and liver protective effect obviously is better than these two kinds of medicines and is used to improve the animal pattern liver function as activating agent separately.
Embodiment 3 acute toxicity tests
Laboratory animal: Kunming mouse, male.China Medicine University's Experimental Animal Center provides, the animal quality certification number: No. 200501002, Soviet Union's moving (matter).
Experiment medicine: magnesium isoglycyrrhetate, kurarinone.Provide lot number by the honest day research and development centre of fine Pharmacy stock Co., Ltd in Jiangsu Chinese medicine laboratory: 051002.
Require to test according to acute toxicity test.Draw the LD of following each group experiment medicine respectively
50Value,
Table 3, magnesium isoglycyrrhetate and kurarinone different proportion compositions acute toxicity test in mice LD
50 
Annotate: " hardship " expression kurarinone; " different sweet " expression magnesium isoglycyrrhetate.It between kurarinone and the magnesium isoglycyrrhetate mass ratio.
Can know the compositions LD of kurarinone and magnesium isoglycyrrhetate by The acute toxicity tests
50Value is apparently higher than the LD of kurarinone and magnesium isoglycyrrhetate
50, show by the mutual synergism between the compositions, reduced the toxicity of medicine.
By analyze the proportionate relationship of magnesium isoglycyrrhetate and kurarinone in dose-effect relationship in embodiment 1,2 pharmacodynamic experiments and each compositions, can know draw in the content of the present invention about magnesium isoglycyrrhetate and kurarinone proportionate relationship preferably and the liver protective effect that has obviously strengthened medicine by the synergism between the medicine that this combination reached.And by our magnesium isoglycyrrhetate and kurarinone combination back LD as can be known of toxicology test data
50Raise, toxicity reduces.
Embodiment 4 magnesium isoglycyrrhetates and kurarinone different proportion composition injection
Taking by weighing each 5.0 gram of magnesium isoglycyrrhetate and kurarinone adds in the 500ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.1g sodium chloride, be stirred to molten entirely, regulate pH to 7.8 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH value to 7.8, through 0.22 μ m filtering with microporous membrane, embedding is in the 10ml ampoule, 100 ℃, the 30min sterilization promptly gets every small-volume injection that contains 100mg magnesium isoglycyrrhetate and kurarinone (1: 1).
Embodiment 5 magnesium isoglycyrrhetates and kurarinone different proportion composition capsule
Get magnesium isoglycyrrhetate 150g and kurarinone 50g and pregelatinized Starch 100g, 80 mesh sieves are crossed in oven dry respectively, put in the mixing machine and mixed 25 minutes, add Stepanol MG 3g, continued mixing 5 minutes, measure content, canned in hard capsule case, make 1000 capsules.
Embodiment 6 magnesium isoglycyrrhetates and kurarinone different proportion composition soft
Step 1: take by weighing gelatin 80g and add the gelatin retort, under condition of stirring, add an amount of water (80g), airtight, after treating that gelatin dissolves fully, add glycerol (24.6g) and an amount of antiseptic again, stir, vacuumize degassing 2 hours, put into the gelatin heat-preserving container, the insulation standing over night, stand-by.
Step 2: oil with hydrogenated soybean (8g), yellow beeswax (8g) are added in the Oleum Arachidis hypogaeae semen (200g), and heating makes the Cera Flava dissolving, and stirring obtains the Oleum Arachidis hypogaeae semen mixture.Take by weighing magnesium isoglycyrrhetate 50g, kurarinone 30g, comminution by gas stream with above-mentioned Oleum Arachidis hypogaeae semen mixture mixing, is put in the colloid mill and fully ground, and makes suspendible even, and is standby.
Step 3: the medicinal liquid that step 1, two prepares is poured in the medicinal liquid bucket, changed mould and begin to press soft capsule, adjust the soft capsule device to scope of design, drying at room temperature two days, the capsule of rejecting the presentation quality difference, soft capsule gets product.
Embodiment 7 magnesium isoglycyrrhetates and kurarinone different proportion composition sustained-release sheet
Prescription
Magnesium isoglycyrrhetate 125g
Kurarinone 100g
Hypromellose 500g
Microcrystalline Cellulose 10g
No. 2 40g of 20% acrylic resin
Magnesium stearate 16g
Coating solution
Opadry (Y-1-7000) 24g
85% ethanol 370g
Plain sheet method for making: magnesium isoglycyrrhetate, kurarinone, hypromellose, microcrystalline Cellulose are crossed 80 mesh sieves, and mixing adds No. 2 systems of 20% acrylic resin soft material, crosses 20 mesh sieve granulate, adds the magnesium stearate mix homogeneously, tabletting, promptly.
Coated tablet: get 85% ethanol 370g, magnetic agitation makes liquid level produce whirlpool, slowly in whirlpool, add Opadry, to dissolving, continue to stir 40 minutes, label is put into coating pan be heated to about 40 ℃, spray into coating solution in the rotation, spouting velocity is 3-5g/min, finishes until whitewashing, dries to get final product.
Embodiment 8 magnesium isoglycyrrhetates and kurarinone different proportion composition granule
Prescription
Magnesium isoglycyrrhetate 65g
Kurarinone 25g
Sodium carboxymethyl cellulose 80g
Aspartame 3g
Cane sugar powder 200g
Mannitol 211.5g
Cocoanut flavour 0.5g
Make 1000 bags altogether
Method for making: magnesium isoglycyrrhetate, kurarinone were pulverized 100 mesh sieves; Sodium carboxymethyl cellulose, aspartame, cane sugar powder, mannitol were pulverized 80 mesh sieves; Getting 50% cane sugar powder adds the suitable quantity of water dissolving and makes syrup; Get residue cane sugar powder, sodium carboxymethyl cellulose, aspartame, mannitol, magnesium isoglycyrrhetate is put mixing in the mixing machine, sprays into syrup system soft material, 15 mesh sieves are granulated, dry, 40 mesh sieve granulate add cocoanut flavour in the granule mix homogeneously, check, packing, promptly.
Embodiment 9 magnesium isoglycyrrhetates and kurarinone different proportion composition dripping
Prescription
Magnesium isoglycyrrhetate 10g
Kurarinone 5g
Polyethylene Glycol 32g
Distilled water 3g
Make 1000 balls altogether
Method for making: kurarinone, magnesium isoglycyrrhetate and polyethylene glycol 6000 pulverize separately are crossed 60 mesh sieves, mix homogeneously, heating in water bath is to the whole fusions of polyethylene glycol 6000, add distilled water, stir, get feed liquid, feed liquid is transferred in the drop pill receiver, airtight and be incubated 90 ℃.Control valve from top to bottom, splashes in the 10-15 ℃ of dimethicone liquid coolant feed liquid, drips to make ball, oil removing, drying.Promptly.
Embodiment 10 magnesium isoglycyrrhetates and kurarinone different proportion compositions enteric coatel tablets
Prescription
Plain sheet
Magnesium isoglycyrrhetate 75g
Kurarinone 75g
Microcrystalline Cellulose 60g
Lactose 24g
Carboxymethyl starch sodium 1.4g
Magnesium stearate 0.6g
Micropowder silica gel 4.2g
Coating solution
Eudragit E udragit L 200g
Pulvis Talci 18g
Water 772g
Make 1000 altogether
Plain sheet: kurarinone, magnesium isoglycyrrhetate, microcrystalline Cellulose, lactose, carboxymethyl starch sodium, magnesium stearate, micropowder silica gel pulverize separately are crossed 100 mesh sieves.Magnesium stearate, micropowder silica gel by equivalent multiplication method and the abundant mixing of kurarinone, magnesium isoglycyrrhetate, carboxymethyl starch sodium, microcrystalline Cellulose and lactose, are crossed 100 mesh sieves three times.With the direct pressed powder of above-mentioned material, promptly.
Coated tablet: get Eudragit E udragit L and add the about 200g of water, stirring and evenly mixing.Add Pulvis Talci in surplus water, magnetic agitation makes even suspendible.The Pulvis Talci suspension is slowly poured in the Eudragit E udragit L aqueous dispersion, was stirred at a slow speed 30 minutes, will join coating solution filter through 80 mesh sieves.Label is put into coating pan and is heated to about 30-35 ℃, sprays into coating solution in the rotation, and spouting velocity is 4-6g/min, finishes until whitewashing, dries promptly.
Embodiment 11 magnesium isoglycyrrhetates and kurarinone different proportion compositions micropill
Prescription
Magnesium isoglycyrrhetate 40g
Kurarinone 30g
Medicinal fine pellet core (cane sugar type) 150g
Hypromellose 10g
Polyethylene glycol 6000 1.0g
Make 1000 altogether
Method for making:, standby with magnesium isoglycyrrhetate, kurarinone micronization; Press recipe quantity with medicine, hypromellose, polyethylene glycol 6000, add suitable quantity of water and make suspension, standby; By recipe quantity fine pellet core (cane sugar type) is put into fluid bed, make its fluidisation, suspension is slowly sprayed into, make the pastille micropill.Canned capsule behind the mensuration content.
Embodiment 12 magnesium isoglycyrrhetates and kurarinone different proportion composition sustained-release micropill
Prescription
Magnesium isoglycyrrhetate 40g
Kurarinone 70g
Medicinal fine pellet core 250g
Hypromellose 18g
Polyethylene glycol 6000 2g
Sulisi 100g
Make 1000 altogether
Method for making:, standby with magnesium isoglycyrrhetate, kurarinone micronization; Press recipe quantity with medicine, hypromellose, polyethylene glycol 6000, add suitable quantity of water and make suspension, standby; By recipe quantity medicinal fine pellet core (cane sugar type) is put into fluid bed, make its fluidisation, suspension is slowly sprayed into, make the pastille micropill; By recipe quantity Sulisi is added suitable quantity of water, be made into coating solution; In the fluid bed, continue coating solution is slowly sprayed into, make slow-release micro-pill.Fill capsule behind the mensuration content.
Embodiment 13 magnesium isoglycyrrhetates and kurarinone different proportion composition injection
Take by weighing in magnesium isoglycyrrhetate, each 2.0g adding 550ml fresh water for injection of kurarinone, the heating in water bath stirring and dissolving, add 9.0g sodium chloride stirring and dissolving, regulate pH to 7.7 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5h then, filtered while hot is settled to 1000ml with fresh water for injection again, with ammonia check and correction pH to 7.7, through 0.22 μ m filtering with microporous membrane.Embedding is rolled lid in 50ml, 100ml, 250ml infusion bottle, 110 ℃ * 30min sterilization promptly makes the high capacity vein transfusion that contains 100ml, 200ml, 500ml kurarinone and Isoglycyrrhiza acid magnesium compositions respectively.
Embodiment 14 magnesium isoglycyrrhetates and kurarinone different proportion compositions ordinary tablet
Prescription:
Magnesium isoglycyrrhetate 40g
Kurarinone 20g
Lactose 50g
Carboxymethyl starch sodium 10g
Magnesium stearate 0.5g
80% ethanol is an amount of
Make 1000 altogether
Method for making: get magnesium isoglycyrrhetate, 80 ℃ of oven dry of kurarinone, cross 80 mesh sieves, standby.Get lactose in 100 ℃ of oven dry, cross 80 mesh sieves, standby.Get the above-mentioned fine powder after sieving, cross sieve twice No. 3, mix homogeneously is put into mixer with blended powder, spray into 80% ethanol while stirring, stir 15min and make soft material, granulation, wet grain is at 80 ℃ of oven dry down, granulate, add carboxymethyl starch sodium, magnesium stearate, mixing, tabletting, promptly.
Embodiment 15 magnesium isoglycyrrhetates and kurarinone different proportion composition oral liquid
Prescription
Magnesium isoglycyrrhetate 4g
Kurarinone 1g
Stevioside 1.5g
Sodium benzoate 0.1g
Purified water 1000ml
Method for making; Get magnesium isoglycyrrhetate and kurarinone, pulverized 100 mesh sieves, add in the purified water, suitably regulate pH value to all dissolvings with sodium hydroxide solution, add stevioside, sodium benzoate, stir and make dissolving, standardize solution filters, embedding, and microwave sterilizating, packing, promptly.
The ordinary tablet of embodiment 16 Isoglycyrrhiza acid diammonium and kurarinone compositions
Prescription:
Isoglycyrrhiza acid diammonium 50g
Kurarinone 15g
Lactose 50g
Carboxymethyl starch sodium 10g
Magnesium stearate 0.5g
80% ethanol is an amount of
Make 1000 altogether
Method for making: get Isoglycyrrhiza acid diammonium, 80 ℃ of oven dry of kurarinone, cross 80 mesh sieves, standby.Get lactose in 100 ℃ of oven dry, cross 80 mesh sieves, standby.Get the above-mentioned fine powder after sieving, cross sieve twice No. 3, mix homogeneously is put into mixer with blended powder, spray into 80% ethanol while stirring, stir 15min and make soft material, granulation, wet grain is at 80 ℃ of oven dry down, granulate, add carboxymethyl starch sodium, magnesium stearate, mixing, tabletting, promptly.
The capsule of embodiment 17 Isoglycyrrhiza acid diammonium and kurarinone compositions
Get Isoglycyrrhiza acid diammonium 150g and kurarinone 50g and pregelatinized Starch 100g, 80 mesh sieves are crossed in oven dry respectively, put in the mixing machine and mixed 25 minutes, add Stepanol MG 3g, continued mixing 5 minutes, measure content, canned in hard capsule case, make 1000 capsules.
The granule of embodiment 18 Isoglycyrrhiza acid diammonium and kurarinone compositions
Prescription
Isoglycyrrhiza acid diammonium 65g
Kurarinone 25g
Sodium carboxymethyl cellulose 80g
Aspartame 3g
Cane sugar powder 200g
Mannitol 211.5g
Cocoanut flavour 0.5g
Make 1000 bags altogether
Method for making: Isoglycyrrhiza acid diammonium, kurarinone were pulverized 100 mesh sieves; Sodium carboxymethyl cellulose, aspartame, cane sugar powder, mannitol were pulverized 80 mesh sieves; Getting 50% cane sugar powder adds the suitable quantity of water dissolving and makes syrup; Get residue cane sugar powder, sodium carboxymethyl cellulose, aspartame, mannitol, the Isoglycyrrhiza acid diammonium is put mixing in the mixing machine, sprays into syrup system soft material, 15 mesh sieves are granulated, dry, 40 mesh sieve granulate add cocoanut flavour in the granule mix homogeneously, check, packing, promptly.
Claims (9)
1. pharmaceutical composition, feature is made up of the derivant of Isoglycyrrhiza acid of treatment effective dose and kurarinone and an amount of acceptable accessories or carrier, the derivant of described Isoglycyrrhiza acid is meant the magnesium salt of Isoglycyrrhiza acid, the ammonium salt of Isoglycyrrhiza acid, the derivant of Isoglycyrrhiza acid: the mass ratio of kurarinone is 1: 10-10: between 1.
2. pharmaceutical composition according to claim 1, feature are that the content of the derivant of Isoglycyrrhiza acid is 30-3000mg, and the content of kurarinone is 20-2000mg.
3. pharmaceutical composition according to claim 1, feature are that the content of the derivant of Isoglycyrrhiza acid is 50-2000mg, and the content of kurarinone is 100-1500mg.
4. pharmaceutical composition according to claim 1, feature are that the content of the derivant of Isoglycyrrhiza acid is 100-1000mg, and the content of kurarinone is 300-1000mg.
5. according to the described arbitrary compositions of claim 1-4, feature is that the derivant of Isoglycyrrhiza acid is the magnesium salt of Isoglycyrrhiza acid.
6. according to the described arbitrary compositions of claim 1-4, be oral formulations, injection, percutaneous dosing or mucosa delivery preparation.
7. compositions according to claim 6, feature are that oral formulations is tablet, powder, granule, capsule, drop pill, oral liquid, pellet.
The described arbitrary compositions of claim 1-4 preparation prevention and treatment hepatitis or with the medicine of hepatitis relevant disease or tumor in application.
9. the described application of claim 7, feature are that hepatitis is human hepatitis B.
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| CN2006100400495A CN101062047B (en) | 2006-04-29 | 2006-04-29 | Combination including isoglycyrrhizinate and oxymatrine and the purpose thereof |
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| CN101062047B true CN101062047B (en) | 2010-06-09 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1381463A (en) * | 2002-05-16 | 2002-11-27 | 吴锡铭 | Magnesium isoglycyrrhetate and its preparing process and usage |
| CN1712411A (en) * | 2004-06-22 | 2005-12-28 | 江苏恒瑞医药股份有限公司 | Compound salt of glycyrrhizin and kurarinol, its production and use |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1381463A (en) * | 2002-05-16 | 2002-11-27 | 吴锡铭 | Magnesium isoglycyrrhetate and its preparing process and usage |
| CN1712411A (en) * | 2004-06-22 | 2005-12-28 | 江苏恒瑞医药股份有限公司 | Compound salt of glycyrrhizin and kurarinol, its production and use |
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| CN101062047A (en) | 2007-10-31 |
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