CN1985927A

CN1985927A - Medicine composition for treating hepatic disease mainly

Info

Publication number: CN1985927A
Application number: CN 200510045377
Authority: CN
Inventors: 黄振华
Original assignee: Individual
Current assignee: Haian Su Fu Technology Transfer Center Co Ltd
Priority date: 2005-12-19
Filing date: 2005-12-19
Publication date: 2007-06-27
Anticipated expiration: 2025-12-19
Also published as: CN1985927B

Abstract

The present invention belongs to the field of medicine technology, and is especially one kind of medicine composition for treating liver diseases and its preparation process. The medicine composition is prepared with wolfberry fruit 50- 1000 weight portions, angelica 50-1000 weight portions, and glycyrrhizic acid or its pharmaceutically acceptable salt 1-50 weight portions; or with wolfberry fruit polysaccharide 2.5-50 weight portions, angelica polysaccharide 1-20 weight portions, and glycyrrhizic acid or its pharmaceutically acceptable salt 1-50 weight portions. It may be prepared into any pharmaceutically acceptable forms, preferably orally taken preparation and injection. It is used mainly for treating various liver diseases, including viral hepatitis, medicinal liver injury, fatty liver, alcohol liver, etc.

Description

A kind of pharmaceutical composition that is mainly used in hepatic disease

1, technical field

The invention belongs to medical technical field, relate to a kind of pharmaceutical composition of mainly making by Fructus Lycii or its extract, Radix Angelicae Sinensis or its extract and glycyrrhizic acid or its pharmaceutically acceptable salt, and preparation method thereof.

2, background technology

Hepatitis is a kind of commonly encountered diseases and frequently-occurring disease, and according to incompletely statistics, China's hepatitis and virus carrier account for 10% of total population.Wherein based on viral hepatitis, viral hepatitis can be divided into again: acute hepatitis, chronic hepatitis, hepatitis gravis and gallbladder type hepatitis.Hepatitis is a kind of infectious disease, because it is popular extensively, hazardness is big, sickness rate is high, is one of difficult and complicated illness of generally acknowledging both at home and abroad at present.China is the high popular district of hepatitis B, has the people above 40% infected by hepatitis B virus (HBV), and it is chronic HBsAg carrier that population more than 100,000,000 is arranged.The hepatitis B cure rate is 10% only, and the overwhelming majority transfers chronic hepatitis to, serious hepatic ascites, the hepatocarcinoma of being converted into.Wherein, the formation and development of hepatic fibrosis is to influence one of crucial pathological change of prognosis and state of an illness commentaries on classics danger, also is the most complicated knotty problem in the clinical chronic hepatopathy treatment.Though it is many that domestic and international medicine for the treatment of hepatitis in recent years has, curative effect is unsatisfactory mostly, treat the back state of an illness easily repeatedly, and price is very expensive again.So far, still lack anti-hepatitis determined curative effect on the market, the medicine that side effect is less again.

Fructus Lycii is the dry mature fruit of plant of Solanaceae lycium barbarum Lvcium barbarum L..Sweet in the mouth, property is flat, returns liver, kidney channel, has effects such as nourishing the liver and kidney, replenishing vital essence to improve eyesight.Fructus Lycii contains lycium barbarum polysaccharide, several amino acids, trace element, vitamin, taurine, alkaloid, volatile oil isoreactivity composition, it is generally acknowledged its main effective ingredient be lycium barbarum polysaccharide (Lycium barbarum polysaccharides, LBP).The modern pharmacology experimental study shows, Fructus Lycii has the effect that serum glutamic pyruvic transminase (ALT) raises due to the obvious inhibition ethanol, and the hepatic injury that heavy drinking is caused has protective effect; The ALT that the Fructus Lycii water decoction can effectively reduce the mice that carbon tetrachloride causes raises, and the hepatic injury due to the Abensanil has protective effect; The Fructus Lycii crude polysaccharides can obviously suppress the mice serum glutamate pyruvate transaminase (ALT) that carbon tetrachloride causes and the rising of glutamic oxaloacetic transaminase, GOT (AST), and can improve and recover each pathological index; Lycium barbarum polysaccharide can make the ALT value due to the carbon tetrachloride raise obviously to reduce, can improve the alcoholic liver disease rat model the mitochondrion form, alleviate hepatic cell fattydegeneration and inflammation degree of necrosis.

When the dry root that is classified as umbelliferae angelica Angelica sinensis (Oliv.) Diels.Sweet in the mouth, suffering, warm in nature, return liver, the heart, spleen channel, effects such as having enriches blood invigorates blood circulation, menstruction regulating and pain relieving, loosening bowel to relieve constipation.The chemical constituent of Radix Angelicae Sinensis can be divided into volatile oil and water-soluble substances two parts.Contain kind of chemical compound surplus ligustilide (ligustilide) and the butylidenephalide (n-butylidene phthalide) etc. 30 in the volatile oil, and serve as (account for volatile oil 45%) at most with ligustilide content, the n-butene lactone then is special fragrance component.Contain ferulic acid, Radix Angelicae Sinensis polysaccharide, Yan acid, folic acid, folinic acid, biotin, succinic acid, uracil and adenine etc. in the water soluble ingredient.The modern pharmacology experimental study shows that hepatic injury has protective effect to Radix Angelicae Sinensis to the carbon tetrachloride induced mice, can alleviate the degree of hepatic fibrosis of hepatic injury rat due to the carbon tetrachloride; Radix Angelicae Sinensis extract has the certain protection effect to multiple hepatic injury; (Angelica sinensis polysaccharides, ASP) hepatic injury has good protective action to Radix Angelicae Sinensis polysaccharide to mouse carbon tetrachloride.

(glycyrrbizie acid is one of the main effective ingredient of the root and rhizome of glycyrrhizic legume, Glycyrrhiza glabra L., Glycyrrhiza inflata Bat. GA) to glycyrrhizic acid, has effects such as antiinflammatory, antiviral, protecting liver and detoxication and raise immunity.Glycyrrhizic acid has the pharmacological action of glucocorticoid sample, can improve the concentration of hepatitis patient serum's hydrocortisone, reduce interleukin-6 and tumor necrosis factor in chronic hepatitis patient serum and the periphery mononuclearcell, alleviate the immunopathogenesis reaction, promote liver function recovery, remove symptom, dwindle hepatosplenomegaly, it is fast to fall enzyme, and the jaundice eliminating subcutaneous ulcer is remarkable.Monoammonium glycyrrhizinate and diammonium glycyrrhizinate are respectively the mono-ammonium and the di-ammonium salts of glycyrrhizic acid.Monoammonium glycyrrhizinate A and monoammonium glycyrrhizinate S are written into national drug standards chemical drugs provincial standard the 12 and the 13 of national standard of rising (Chinese Pharmacopoeia Commission's volume) respectively, wherein regulation: press dry product and calculate, contain monoammonium glycyrrhizinate (C ₄₂H ₆₁O ₁₆NH ₄) must not be less than 67.0% and 73.0% respectively.Monoammonium glycyrrhizinate has certain auxiliary treatment effect to various acute, chronic hepatitis, hepatic fibrosis, toxic hepatitis, traumatic hepatitis.Diammonium glycyrrhizinate is the positive oleanane of 20 β-carboxyl-11 oxo-12-alkene-3 β base-2-β-D-glucopyranoside aldehydic acid base-α-D-glucopyranoside aldehydic acid di-ammonium salts, loaded national drug standards new drug the 43rd of the standard (Chinese Pharmacopoeia Commission's volume) of becoming a full member, wherein stipulate: press dry product and calculate, contain C ₄₂H ₆₈N ₂O ₁₆Should be 97.0%～103.0%.Diammonium glycyrrhizinate is the third generation extract of Chinese medicine effective liquorice, has stronger antiinflammatory, protects liver plasma membrane and improves the effect of liver function; Pharmacological evaluation proves, mice is oral to alleviate the serum glutamic pyruvic transminase and the glutamic oxaloacetic transaminase, GOT that cause because of carbon tetrachloride, thioacetamide and D-Gal and raises, and can also obviously alleviate the amino gala acid of D-to the form damage of liver with improve the chronic injury of immune factor to the liver form.

At present, utilize the interaction of Fructus Lycii or its extract, Radix Angelicae Sinensis or its extract and glycyrrhizic acid or its pharmaceutically acceptable salt, composition of prescription, preparation is used for the treatment of the medicine of hepatic disease aspect, does not appear in the newspapers as yet.

3, summary of the invention

In order to meet clinical needs; better treat hepatic disease; delay or reduce the conversion of hepatitis to hepatic ascites or hepatocarcinoma; improve the quality of life of hepatitis; the invention provides a kind of pharmaceutical composition that is mainly used in the treatment hepatic disease and preparation method thereof; mainly by Fructus Lycii or its extract; Radix Angelicae Sinensis or its extract and glycyrrhizic acid or its pharmaceutically acceptable salt are made; to carbon tetrachloride; chmice acute hepatic injury due to the acetaminophen; the rat chronic hepatic injury of tetrachloro-methane induction; the inductive mice chronic hepatic injury of ethanol all has significant protective effect; and can significantly suppress DHB, produce beyond thought effect.

Pharmaceutical composition of the present invention is mainly made by Fructus Lycii, Radix Angelicae Sinensis and glycyrrhizic acid or its pharmaceutically acceptable salt, its parts by weight are 1～50 part of 50～1000 parts of Fructus Lycii, 50～1000 parts of Radix Angelicae Sinensis, glycyrrhizic acid or its pharmaceutically acceptable salt, be preferably 2～30 parts of 100～500 parts of Fructus Lycii, 100～500 parts of Radix Angelicae Sinensis, glycyrrhizic acid or its pharmaceutically acceptable salts, more preferably 200 parts of Fructus Lycii, 200 parts of Radix Angelicae Sinensis, glycyrrhizic acid or its pharmaceutically acceptable salt are 4～15 parts.

The glycyrrhizic acid pharmaceutically acceptable salt can be slaine or organic nitrogen salt in the aforementioned pharmaceutical compositions, and slaine can be sodium salt, potassium salt, magnesium salt, calcium salt, zinc salt, and organic nitrogen salt can be mono-ammonium, di-ammonium salts; Be preferably monoammonium glycyrrhizinate and diammonium glycyrrhizinate.The optimum parts by weight of Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate are: 200 parts of Fructus Lycii, 200 parts of Radix Angelicae Sinensis, 4 parts of monoammonium glycyrrhizinates, the optimum parts by weight of Fructus Lycii, Radix Angelicae Sinensis, diammonium glycyrrhizinate are: 200 parts of Fructus Lycii, 200 parts of Radix Angelicae Sinensis, 15 parts of diammonium glycyrrhizinates.

Fructus Lycii in the aforementioned pharmaceutical compositions, Radix Angelicae Sinensis can with The suitable solvent and method separately or mixed extraction processing obtain extract, total extract is made clinically arbitrary or pharmaceutically acceptable dosage form with glycyrrhizic acid or its pharmaceutically acceptable salt and mixing acceptable accessories again." extract separately " and be meant that Fructus Lycii, each flavor medical material of Radix Angelicae Sinensis extract separately by different technology respectively and obtain extract, each extract are mixed obtaining total extract again." mixed extraction " is meant, Fructus Lycii, Radix Angelicae Sinensis two flavor medical materials extract together and obtain total extract.Contained main effective ingredient is lycium barbarum polysaccharide and Radix Angelicae Sinensis polysaccharide in the total extract of gained, and the total content of main effective ingredient preferably is not less than 50%.

In the preparation method of aforementioned pharmaceutical compositions, used solvent is meant solvent pharmaceutically commonly used, can be water or ethanol etc.; Used method is meant the conventional method of Chinese medicine extraction, can be decocting method, reflux extraction, infusion process, percolation or continuous extraction etc.For example, Fructus Lycii can extract with decocting method, reflux extraction, decoction and alcohol sedimentation technique and prepare lycium barbarum polysaccharide, Radix Angelicae Sinensis can extract with decocting method, infusion process, decoction and alcohol sedimentation technique and prepare Radix Angelicae Sinensis polysaccharide, and Fructus Lycii and Radix Angelicae Sinensis can be obtained through refining altogether with decocting method, reflux extraction, decoction and alcohol sedimentation technique and obtain total polysaccharides fully.

The concrete preparation method of crude drug is as follows:

The invention provides a kind of preferred extraction process (is main effective ingredient with polysaccharide) of Fructus Lycii, as follows:

Get the Fructus Lycii medical material, add 80% alcohol reflux secondary, each 2 hours, filter, discard behind the filtrate recycling ethanol.Medicinal residues decoct with water three times, each 1 hour, filter, filtrate decompression is concentrated into relative density 1.10～1.12 (60 ℃), puts coldly, and cold preservation is put and left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, stir adding concentrated hydrochloric acid adjust pH to 1～2 down, cold preservation is put and was left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, with 4 times of volume of ethanol precipitations, after 24 hours, the leaching precipitation gets crude polysaccharides in refrigerator cold-storage.Crude polysaccharides adds the suitable quantity of water dissolving, filters, and filtrate adds 2% active carbon, be heated to 80 ℃ and be incubated 20 minutes, filter while hot, filtrate is concentrated into relative density 1.14～1.16 (60 ℃), adds 4 times of volume of ethanol precipitations, cold preservation is sucking filtration after 24 hours, precipitation is used dehydrated alcohol, acetone, and each washing of ether is once, vacuum drying below 60 ℃, promptly.Lycium barbarum polysaccharide yield by this prepared is 5～6%, and the content of polysaccharide is not less than 80%.

Fructus Lycii can also extract preparation by following technology, but is not limited only to following technology:

Technology one: get the Fructus Lycii medical material, put in the apparatus,Soxhlet's, use the alcohol reflux 4 hours of petroleum ether, ether and 80% successively, after residue volatilizes solvent, add the water reflux, extract, again 4 hours, be evaporated to half volume, add 0.1% activated carbon decolorizing 2 times, sucking filtration, filtrate add ethanol to be made and contains alcohol amount and reach 80%, and cold preservation is spent the night, filter, precipitation is used dehydrated alcohol, ether, washing with acetone successively, vacuum drying below 60 ℃, promptly.Lycium barbarum polysaccharide yield by this prepared is 6～8%, and the content of polysaccharide is not less than 50%.

Technology two: get the Fructus Lycii medical material, add the cold water lixiviate three times, each 1 hour, add 10 times of amounts of water for the first time, second and third time respectively adds 8 times of amounts of water, merge extractive liquid, filters, and filtrate decompression is concentrated into relative density 1.10～1.12 (60 ℃), put cold, add ethanol and make that to contain amount of alcohol be 70%, standing over night filters, decompression filtrate recycling ethanol and to be concentrated into relative density be 1.12～1.14 (60 ℃), add 3 times of water gagings, fully stir cold preservation 48 hours, filter, it is 1.14～1.16 (60 ℃) that filtrate decompression is concentrated into relative density, vacuum drying below 60 ℃, promptly.Lycium barbarum polysaccharide yield by this prepared is 7～10%, and the content of polysaccharide is not less than 30%.

The invention provides a kind of preferred extraction process (is main effective ingredient with Radix Angelicae Sinensis polysaccharide) of Radix Angelicae Sinensis, as follows:

Get the Radix Angelicae Sinensis medical material, add 80% alcohol reflux secondary, each 2 hours, filter, discard behind the filtrate recycling ethanol.Medicinal residues decoct with water three times, each 1 hour, filter, filtrate decompression is concentrated into relative density 1.10～1.12 (60 ℃), puts coldly, and cold preservation is put and left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, stir adding concentrated hydrochloric acid adjust pH to 1～2 down, cold preservation is put and was left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, with 4 times of volume of ethanol precipitations, after 24 hours, the leaching precipitation gets crude polysaccharides in refrigerator cold-storage.Crude polysaccharides adds the suitable quantity of water dissolving, filter, filtrate adds 2% active carbon, is heated to 80 ℃ and be incubated 20 minutes, filters while hot, filtrate is concentrated into relative density 1.14～1.16 (60 ℃), add 4 times of volume of ethanol precipitations, cold preservation is sucking filtration after 24 hours, and precipitation with dehydrated alcohol, acetone, each washing of ether once, vacuum drying below 60 ℃, promptly.Radix Angelicae Sinensis polysaccharide yield by this prepared is 1～3%, and the content of polysaccharide is not less than 80%.

Can extract preparation by following technology when giving back, but be not limited only to following technology:

Technology one: get the Radix Angelicae Sinensis medical material, add 85 ℃ of floodings of 10 times of amounts three times, each 2 hours, merge extractive liquid, filters, and filtrate decompression is concentrated into relative density 1.10～1.12 (60 ℃), put coldly, cold preservation was left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, add chloroform-n-butanol extraction residual protein and oils and fats, place in 60% ethanol and spend the night, leach precipitation, successively with dehydrated alcohol, acetone, ether washing, vacuum drying below 60 ℃, promptly.Radix Angelicae Sinensis polysaccharide yield by this prepared is 3～5%, and the content of polysaccharide is not less than 40%.

Technology two: get the Radix Angelicae Sinensis medical material, decoct with water secondary, each 2 hours, collecting decoction filters, and it is 1.10～1.12 (60 ℃) that filtrate decompression is concentrated into relative density, put coldly, add ethanol and make that to contain amount of alcohol be 65%, standing over night, filter, decompression filtrate recycling ethanol and to be concentrated into relative density be 1.12～1.14 (60 ℃) adds 3 times of water gagings, fully stir, cold preservation 48 hours filters, and it is 1.14～1.16 (60 ℃) that filtrate decompression is concentrated into relative density, add ethanol and make that to contain amount of alcohol be 85%, standing over night filters, the precipitation dehydrated alcohol, acetone, each washs ether once, vacuum drying below 60 ℃, promptly.Radix Angelicae Sinensis polysaccharide yield by this prepared is 4～6%, and the content of polysaccharide is not less than 30%.

The invention provides the selection process (is main effective ingredient with lycium barbarum polysaccharide and Radix Angelicae Sinensis polysaccharide) that a kind of Fructus Lycii and Radix Angelicae Sinensis are carried altogether, as follows:

Get Fructus Lycii, Radix Angelicae Sinensis medical material, add 80% alcohol reflux secondary, each 2 hours, filter, discard behind the filtrate recycling ethanol.Medicinal residues decoct with water three times, each 1 hour, filter, filtrate decompression is concentrated into relative density 1.10～1.12 (60 ℃), puts coldly, and cold preservation is put and left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, stir adding concentrated hydrochloric acid adjust pH to 1～2 down, cold preservation is put and was left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, with 4 times of volume of ethanol precipitations, after 24 hours, the leaching precipitation gets crude polysaccharides in refrigerator cold-storage.Crude polysaccharides adds the suitable quantity of water dissolving, filters, and filtrate adds 2% active carbon, be heated to 80 ℃ and be incubated 20 minutes, filter while hot, filtrate is concentrated into relative density 1.14～1.16 (60 ℃), adds 4 times of volume of ethanol precipitations, cold preservation is sucking filtration after 24 hours, precipitation is used dehydrated alcohol, acetone, and each washing of ether is once, vacuum drying below 60 ℃, promptly.Putting forward the thing yield altogether by the Fructus Lycii Radix Angelicae Sinensis of this prepared is 3～4%, and the content of total polysaccharides is not less than 80%.

Fructus Lycii and when giving back and can carry altogether by following technology, but be not limited only to following technology:

Technology one: get Fructus Lycii, Radix Angelicae Sinensis medical material, put in the apparatus,Soxhlet's, use the alcohol reflux 4 hours of petroleum ether, ether and 80% successively, after residue volatilizes solvent, add the water reflux, extract, again 4 hours, be evaporated to half volume, add 0.1% activated carbon decolorizing 2 times, sucking filtration, filtrate add ethanol to be made and contains alcohol amount and reach 85%, and cold preservation is spent the night, filter, precipitation is used dehydrated alcohol, ether, washing with acetone successively, vacuum drying below 60 ℃, promptly.Putting forward the thing yield altogether by the Fructus Lycii Radix Angelicae Sinensis of this prepared is 4～6%, and the content of total polysaccharides is not less than 50%.

Technology two: get Fructus Lycii, the Radix Angelicae Sinensis medical material decocts with water secondary, each 2 hours, collecting decoction filters, and it is 1.10～1.12 (60 ℃) that filtrate decompression is concentrated into relative density, put coldly, add ethanol and make that to contain amount of alcohol be 65%, standing over night, filter, decompression filtrate recycling ethanol and to be concentrated into relative density be 1.12～1.14 (60 ℃) is put cold, cold preservation is put and is left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, adding ethanol makes and contains alcohol amount and reach 80%, cold preservation is spent the night, and filters the precipitation dehydrated alcohol, acetone, each washs ether once, vacuum drying below 60 ℃, promptly.Putting forward the thing yield altogether by this prepared Fructus Lycii Radix Angelicae Sinensis is 5～7%, and the content of total polysaccharides is not less than 30%.

Pharmaceutical composition of the present invention can also replace Fructus Lycii, Radix Angelicae Sinensis polysaccharide to replace Radix Angelicae Sinensis to feed intake by lycium barbarum polysaccharide and make.Calculate with respect to the yield of medical material according to extract, the weight portion of each crude drug of pharmaceutical composition of the present invention is 1～50 part of 2.5～50 parts of lycium barbarum polysaccharide, 1～20 part of Radix Angelicae Sinensis polysaccharide, glycyrrhizic acid or its pharmaceutically acceptable salt, be preferably 2～30 parts of 5～25 parts of lycium barbarum polysaccharide, 2～10 parts of Radix Angelicae Sinensis polysaccharides, glycyrrhizic acid or its pharmaceutically acceptable salts, more preferably 10 parts of lycium barbarum polysaccharide, 4 parts of Radix Angelicae Sinensis polysaccharides, glycyrrhizic acid or its pharmaceutically acceptable salt are 4～15 parts.

The glycyrrhizic acid pharmaceutically acceptable salt can be slaine or organic nitrogen salt in the aforementioned pharmaceutical compositions, and slaine can be sodium salt, potassium salt, magnesium salt, calcium salt, zinc salt, and organic nitrogen salt can be mono-ammonium, di-ammonium salts; Be preferably monoammonium glycyrrhizinate and diammonium glycyrrhizinate.The optimum parts by weight of lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide, monoammonium glycyrrhizinate are 10 parts of Qi polysaccharide, 4 parts of Radix Angelicae Sinensis polysaccharides, 4 parts of monoammonium glycyrrhizinates, and the optimum parts by weight of lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide, diammonium glycyrrhizinate are 10 parts of Qi polysaccharide, 4 parts of Radix Angelicae Sinensis polysaccharides, 15 parts of diammonium glycyrrhizinates.

In the aforementioned pharmaceutical compositions, the main effective ingredient of lycium barbarum polysaccharide be polysaccharide, the content of polysaccharide is not less than 30%, preferably is not less than 50%; The main effective ingredient of Radix Angelicae Sinensis polysaccharide is a polysaccharide, and the content of polysaccharide is not less than 30%, preferably is not less than 50%.Lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide all can prepare with reference to preceding method.Main effective ingredient in the total extract that obtains by said ratio is lycium barbarum polysaccharide and Radix Angelicae Sinensis polysaccharide, and the total content of main effective ingredient preferably is not less than 50%.

Pharmaceutical composition of the present invention, the consumption of drug component 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.Above-mentioned composition as if being unit with the gram, can be made the preparation of 10～1000 consumptions, as liquid drugs injection or powder pin, can be made into 10～1000,1～10 of each consumption.As tablet or capsule, can be made into 10～1000, take 1～10 at every turn.Above-mentioned composition is by weight as proportioning, can be unit with kilogram or ton as large-scale production, and small-scale production can be unit with the gram also.Above-mentioned parts by weight are for especial patient, and the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.

Pharmaceutical composition of the present invention can be made clinically arbitrary or pharmaceutically acceptable dosage form, is applied to the patient of this treatment of needs in the mode of oral or parenteral.During oral administration, can be made into oral normal release dosage form (as sheet, enteric coatel tablets, dispersible tablet, chewable tablet, oral cavity disintegration tablet, capsule, soft capsule, enteric coated capsule etc.), sustained-release and controlled release dosage form (as slow releasing tablet, controlled release tablet, slow releasing capsule, controlled release capsule etc.), oral fluid agent (as oral administration solution, syrup etc.), drop pill, granule etc.; During parenteral, can be made into solution, water for injection or the oil-suspending agent etc. of injection.Preferred dosage form is injection and oral formulations, as powder pin, liquid drugs injection, transfusion, sheet, capsule, granule etc.

Aforementioned pharmaceutical compositions, can adopt the conventional method production in the existing pharmaceutical field, various acceptable accessories be can add in case of necessity, diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc. comprised.

Aforementioned pharmaceutical compositions in order to increase its dissolubility, can add solubilizing agents such as Tween-80 when making injection.Can add the isoosmotic adjusting agent that sodium chloride, glucose etc. are used to regulate osmotic pressure in the transfusion.Can add excipient such as mannitol in the powder pin.

Pharmaceutical composition of the present invention is mainly used in the medicine for preparing treating hepatic disease.Pharmacological effect studies show that Fructus Lycii or its extract, Radix Angelicae Sinensis or its extract, glycyrrhizic acid or its pharmaceutically acceptable salt drug combination are to carbon tetrachloride (CCl ₄) and acetaminophen due to mouse liver injury, carbon tetrachloride (CCl ₄) inductive rat chronic hepatic injury, the inductive mice chronic hepatic injury of ethanol all have significant protective effect, and can significantly suppress DHB (DHBV); Point out it aspect antiviral hepatitis, drug induced hepatic injury, fatty liver, the alcoholic liver significant curative effect will arranged.

Pharmaceutical composition of the present invention has following advantage:

(1) provides a kind of new compound recipe Antihepatitis medicament, satisfied urgent clinical needs.

(2) consumption of pharmaceutical composition Chinese medicine component of the present invention has been carried out groping in a large number research, the injection of making by different proportionings is to carbon tetrachloride (CCl ₄) cause the research of the influence of hepatic injury mice serum ALT and AST level, filter out weight proportion with significant curative effect.

(3) pharmacological effect studies show that, the mouse liver injury due to the pharmaceutical composition Abensanil of the present invention has remarkable protective effect, can significantly reduce Serum ALT, GST level and hepatic tissue LPO level; Rat chronic hepatic injury to tetrachloro-methane induction has remarkable protective effect, can significantly reduce Serum ALT and AST level, and the serum ALB level that significantly raises significantly alleviates degree of hepatic fibrosis and reduces the fibrosis incidence rate; The inductive mice chronic hepatic injury of ethanol also there is significant protective effect, can significantly reduces Serum ALT, AST, TG level, alleviate liver tissue lesions; Can significantly suppress DHB (DHBV), the effect of high dose group is suitable with the effect of positive controls, and does not have rebound phenomenon after the drug withdrawal.Produced beyond thought effect.

(4) pharmaceutical composition of the present invention, can feed intake with Fructus Lycii, Radix Angelicae Sinensis, glycyrrhizic acid or its pharmaceutically acceptable salt, can be raw material also, can be made into clinically arbitrary or pharmaceutically acceptable dosage form with lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide, glycyrrhizic acid or its pharmaceutically acceptable salt.

(5) preparation that pharmaceutical composition of the present invention is made or used extract have carried out discriminating, assay, stability study etc., and effective ingredient is clear and definite, content is high, and better stability of preparation is convenient to control product quality, guarantee clinical drug safety.

(6) provide preferable preparation technique, simple and easy to do, and quality of the pharmaceutical preparations height, be adapted to industrialized great production.

Below further set forth the beneficial effect of pharmaceutical composition of the present invention by testing example, these test routine pharmacodynamics test and the stability test that comprises pharmaceutical composition of the present invention.Pharmaceutical composition of the present invention has following beneficial effect, but this should be interpreted as that pharmaceutical composition of the present invention only has following beneficial effect.

Below replacing with lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide, monoammonium glycyrrhizinate with GDG1 in the test example is the pharmaceutical composition of main effective ingredient, and replacing with lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide, diammonium glycyrrhizinate with GDG2 is the pharmaceutical composition of main effective ingredient.Below used lycium barbarum polysaccharide is in the test example Embodiment 1The preparation gained, used Radix Angelicae Sinensis polysaccharide is Embodiment 2The preparation gained, used Fructus Lycii Radix Angelicae Sinensis is carried thing altogether and is Embodiment 3The preparation gained. Test example 2～6In used GDG1 injection, GDG2 injection be Embodiment 4The preparation gained.

Test example 1 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate diammonium glycyrrhizinate and medication cause the influence of mouse liver injury to carbon tetrachloride

The animal subject healthy mice, 240, body weight 20～25g, the male and female dual-purpose is divided into 24 groups at random, 10 every group.

Test sample sodium chloride injection (normal control group): 250ml:2.25g, Shangdong Changfu Jiejing Pharmaceutical Industry Co., Ltd.

The Fructus Lycii injection: self-control, 2ml contains lycium barbarum polysaccharide 110mg (being equivalent to crude drug 2g)

Radix Angelicae Sinensis injection: self-control, 2ml contains Radix Angelicae Sinensis polysaccharide 43mg (being equivalent to crude drug 2g)

Monoammonium glycyrrhizinate injection: self-control, 5ml:40mg

Diammonium glycyrrhizinate injection: self-control, 10ml:150mg

The injection of (Fructus Lycii+Radix Angelicae Sinensis+monoammonium glycyrrhizinate) different proportionings: self-control sees Table 1-1

The injection of (Fructus Lycii+Radix Angelicae Sinensis+diammonium glycyrrhizinate) different proportionings: self-control sees Table 1-1

Dosage sees Table 1-1.

The test method mice is divided into 24 groups at random, 10 every group, is respectively normal control group, model group and each administration group.Normal control group and model group tail vein injection saline 20ml/kg, every day 1 time, continuous 7 days; Each administration group is by the administration of table 1-1 tail vein injection, every day 1 time, continuous 7 days.Behind the last tail vein injection 2h, normal control group lumbar injection Oleum Arachidis hypogaeae semen 10ml/kg, all the other respectively organize equal lumbar injection 0.12% carbon tetrachloride (CCl ₄) peanut oil solution 10ml/kg.The sacrificed by decapitation animal is got blood behind the 16h, and is centrifugal, gets serum, measures serum glutamic pyruvic transminase (ALT) and glutamic oxaloacetic transaminase, GOT (AST) level.After broken end was got blood, hepatic tissue was done the routine pathology histological examination.

Result of the test sees Table 1-1.Compare with the normal control group, the Serum ALT of model group and AST water mean pole significantly raise (p＜0.01), and histopathologic examination finds that hepatic tissue is obviously impaired, and necrosis occurs, and the modeling success is described.Compare with model group, each administration group is to CCl ₄Inductive mouse liver injury all has protective effect, can reduce Serum ALT and AST level, alleviates liver tissue lesions and necrosis; Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, diammonium glycyrrhizinate injection are to CCl ₄Inductive mouse liver injury have a significant protective effect (p＜0.05); 50～1000 parts of Fructus Lyciis, 50～1000 parts of Radix Angelicae Sinensis, monoammonium glycyrrhizinate or 1～50 part of injection of making of diammonium glycyrrhizinate are to CCl ₄Inductive mouse liver injury all has extremely significant protective effect (p＜0.01; p＜0.001); the protective effect of 100～500 parts of Fructus Lycii, 100～500 parts of Radix Angelicae Sinensis, monoammonium glycyrrhizinate or 2～30 parts of injection of making of diammonium glycyrrhizinate is better, and is especially best with the protective effect of 200 parts of Fructus Lycii, 200 parts of Radix Angelicae Sinensis, 4 parts of monoammonium glycyrrhizinates or 15 parts of injection of making of diammonium glycyrrhizinate.

Compare with Fructus Lycii injection group, (Fructus Lycii+Radix Angelicae Sinensis+monoammonium glycyrrhizinate) injection of each proportioning and (Fructus Lycii+Radix Angelicae Sinensis+diammonium glycyrrhizinate) injection are to CCl ₄The protective effect of inductive mouse liver injury all has significant protective effect (p＜0.05, p＜0.01).Compare with Radix Angelicae Sinensis injection, (Fructus Lycii+Radix Angelicae Sinensis+monoammonium glycyrrhizinate) injection of each proportioning and (Fructus Lycii+Radix Angelicae Sinensis+diammonium glycyrrhizinate) injection are to CCl ₄The protective effect of inductive mouse liver injury all has significant protective effect (p＜0.05, p＜0.01).Compare with the monoammonium glycyrrhizinate injection, (Fructus Lycii+Radix Angelicae Sinensis+monoammonium glycyrrhizinate) injection of each proportioning is to CCl ₄The protective effect of inductive mouse liver injury all has significant protective effect (p＜0.05, p＜0.01).Compare with diammonium glycyrrhizinate injection, (Fructus Lycii+Radix Angelicae Sinensis+diammonium glycyrrhizinate) injection of each proportioning is to CCl ₄The protective effect of inductive mouse liver injury all has significant protective effect (p＜0.05).

The conclusion result of the test shows that Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination are to CCl ₄Inductive mouse liver injury has significant protective effect, and under the identical dosage, (Fructus Lycii+Radix Angelicae Sinensis+monoammonium glycyrrhizinate) injection of each proportioning and (Fructus Lycii+Radix Angelicae Sinensis+diammonium glycyrrhizinate) injection are to CCl ₄The protective effect of inductive mouse liver injury all is better than Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, the diammonium glycyrrhizinate injection effect of use separately.Prompting, Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate and medication have synergism, and remarkable effect is being arranged aspect anti-hepatitis, the hepatic injury.

Table 1-1 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination are to CCl ₄The influence of hepatic injury mice

(meansigma methods ± standard deviation, n=10)

Group	Dosage	The crude drug proportioning	ALT(U/L)	AST(U/L)
Group	Dosage	The crude drug proportioning	ALT(U/L)	AST(U/L)	The normal control group	20ml/kg	-	45.05±5.24	237.41±28.03
Model group	20ml/kg	-	252.76±25.13 ^##	417.54±37.79 ^##	The normal control group	20ml/kg	-	45.05±5.24	237.41±28.03
Model group	20ml/kg	-	252.76±25.13 ^##	417.54±37.79 ^##	Fructus Lycii injection group	50mg/kg	-	170.37±23.24 ^*	354.24±32.46 ^*
The Radix Angelicae Sinensis injection group	50mg/kg	-	167.72±22.64 ^*	356.46±33.25 ^*	Fructus Lycii injection group	50mg/kg	-	170.37±23.24 ^*	354.24±32.46 ^*
The Radix Angelicae Sinensis injection group	50mg/kg	-	167.72±22.64 ^*	356.46±33.25 ^*	Monoammonium glycyrrhizinate injection group	50mg/kg	-	165.48±20.15 ^*	328.73±31.27 ^*
The diammonium glycyrrhizinate injection group	50mg/kg	-	157.60±21.31 ^*	314.09±30.76 ^*	Monoammonium glycyrrhizinate injection group	50mg/kg	-	165.48±20.15 ^*	328.73±31.27 ^*
The diammonium glycyrrhizinate injection group	50mg/kg	-	157.60±21.31 ^*	314.09±30.76 ^*	(Fructus Lycii+Radix Angelicae Sinensis+monoammonium glycyrrhizinate) injection group	50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg	0.5g+10g+10mg 1g+5g+20mg 1g+5g+40mg 2g+2g+20mg 2g+2g+40mg 2g+2g+150mg 2g+2g+300mg 5g+1g+300mg 10g+0.5g+500mg	120.73±14.86 ^ace110.29±12.64 ^ace98.29±12.04 ^bdf92.48±11.43 ^bdf81.57±10.76 ^bdf89.26±11.59 ^bdf97.43±11.78 ^bdf107.49±15.23 ^ace118.13±15.42 ^*ace	307.64±30.04 ^ace292.70±29.35 ^ace289.91±26.48 ^*bdf284.67±26.50 ^bdf272.25±25.42 ^bdf278.83±27.17 ^bde287.48±26.84 ^bdf295.63±28.46 ^ace303.47±31.94 ^**ace
(Fructus Lycii+Radix Angelicae Sinensis+diammonium glycyrrhizinate) injection group	50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg 50mg/kg	0.5g+10g+10mg 1g+5g＋20mg 2g+2g+20mg 2g+2g+40mg 2g+2g+150mg 2g+2g+300mg 5g+1g+150mg 5g+1g+300mg 10g+0.5g+500mg	120.02±15.34 ^acg107.58±13.42 ^acg96.19±12.27 ^*bdh87.41±12.62 ^bdh80.54±11.82 ^bdh91.75±13.02 ^bdh94.67±12.13 ^bdh104.94±15.73 ^acg113.81±16.70 ^**acg	306.73±31.62 ^acg293.5 1±28.94 ^acg285.37±25.45 ^bdh279.93±27.87 ^bdh270.43±26.35 ^bdh281.72±28.27 ^bdh284.27±27.13 ^*bdh292.73±27.59 ^acg301.54±29.73 ^*acg

Compare with the normal control group: ^#P＜0.05, ^##P＜0.01; Compare with model group: ^*P＜0.05, ^*P＜0.01, ^{* *}P＜0.001; Compare with Fructus Lycii injection group: ^aP＜0.05, ^bP＜0.01; Compare with the Radix Angelicae Sinensis injection group: ^cP＜0.05, ^dP＜0.01; Compare with monoammonium glycyrrhizinate injection group: ^eP＜0.05, ^fP＜0.01; Compare with the diammonium glycyrrhizinate injection group: ^gP＜0.05, ^hP＜0.01.

Test example 2 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination Abensanil cause the effect of mouse liver injury

The animal subject healthy mice, 120, body weight 20～25g, the male and female dual-purpose is divided into 12 groups at random, 10 every group.

Monoammonium glycyrrhizinate injection: self-control, 5ml:40mg

Diammonium glycyrrhizinate injection: self-control, 10ml:150mg

The GDG1 injection: self-control, 5ml:193mg contains lycium barbarum polysaccharide 110mg (being equivalent to crude drug 2g), Radix Angelicae Sinensis polysaccharide 43mg

(being equivalent to crude drug 2g), monoammonium glycyrrhizinate 40mg

The GDG2 injection: self-control, 5ml:293mg contains the Fructus Lycii Radix Angelicae Sinensis and carries thing 143mg (being equivalent to crude drug Fructus Lycii 2g, Radix Angelicae Sinensis 2g), diammonium glycyrrhizinate 150mg altogether

Dosage sees Table 1-2.

120 of test method mices are divided into 12 groups at random, 10 every group, are respectively normal control group, model group and each administration group.Except that the normal control group, the equal lumbar injection acetaminophen of all the other each treated animals (AP) 100ml/kg, overnight fasting.Normal control group and model group tail vein injection saline every day 20ml/kg, every day 1 time, continuous 10 days; Each administration group is by the administration of table 1-2 tail vein injection, every day 1 time, continuous 10 days.Behind the last tail vein injection 6h, normal control group intraperitoneal injection of saline, all the other respectively organize equal lumbar injection acetaminophen 300mg/kg.Put to death behind the 16h, get blood and liver, measure the lipid peroxide (LPO) of serum glutamic pyruvic transminase (ALT), glutathione S-transferase (GST) and hepatic tissue.

Result of the test sees Table 1-2.Compare with the normal control group, the Serum ALT of model group, GST level and hepatic tissue LPO level significantly raise (p＜0.01), and the modeling success is described.Compare with model group, each administration group Abensanil causes mouse liver injury and all has protective effect, reduces Serum ALT, GST level and hepatic tissue LPO level; Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, diammonium glycyrrhizinate injection Abensanil cause mouse liver injury and have significant protective effect (p＜0.05); each dosage GDG1 injection and GDG2 injection Abensanil cause mouse liver injury and have extremely significant protective effect (p＜0.01, p＜0.001).

Table 1-2 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination Abensanil cause the effect of mouse liver injury

(meansigma methods ± standard deviation, n=10)

Group	Dosage	ALT(U/L)	GST(nmol·min·ml ^-1)	LPO(nmol/L)
Group	Dosage	ALT(U/L)	GST(nmol·min·ml ^-1)	LPO(nmol/L)	Dosage group GDG2 parenteral solution high dose group in the dosage group GDG1 parenteral solution high dose group GDG2 parenteral solution low dose group GDG2 parenteral solution in the Normal group model group matrimony vine parenteral solution group Radix Angelicae Sinensis injection group ammonium glycyrrhizinate parenteral solution group diammonium glycyrrhizinate injection group GDG1 parenteral solution low dose group GDG1 parenteral solution	20ml/kg 20ml/kg 75mg/kg 75mg/kg 75mg/kg 75mg/kg 25mg/kg 50mg/kg 75mg/kg 25mg/kg 50mg/kg 75mg/kg	39.57±5.44 260.48±24.32 ^##167.44±24.03 ^170.24±23.05 ^169.51±22.37 ^161.74±20.38 ^105.46±17.25 ^ace94.76±1 5.34 ^bdf78.51±11.72 ^bdf102.72±16.82 ^acg90.43±15.57 ^*bdh75.37±12.43 ^*bdh	115.7±25.4 508.2±250.3 ^##287.5±164.8 ^290.8±175.4 ^294.6±170.5 ^270.6±173.8 ^195.7±87.7 ^ace176.8±76.4 ^bdf152.4±70.3 ^bdf190.4±82.6 ^acg174.3±77.1 ^*bdh149.8±71.4 ^*bdh	4.57±0.28 8.82±0.61 ^##7.05±0.47 ^7.14±0.36 ^7.34±0.45 ^6.76±0.42 ^5.73±0.44 ^ace5.40±0.39 ^acf5.12±0.32 ^bdf5.65±0.42 ^acg5.33±0.35 ^*acg5.04±0.33 ^*bdh

Compare with the normal control group: ^#P＜0.05, ^##P＜0.01; Compare with model group: ^*P＜0.05, ^*P＜0.01, ^{* *}P＜0.001;

Compare with Fructus Lycii injection group: ^aP＜0.05, ^bP＜0.01; Compare with the Radix Angelicae Sinensis injection group: ^cP＜0.05, ^dP＜0.01;

Compare with monoammonium glycyrrhizinate injection group: ^eP＜0.05, ^fP＜0.01; Compare with the diammonium glycyrrhizinate injection group: ^gP＜0.05, ^hP＜0.01.

The conclusion result of the test shows that Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination Abensanil cause mouse liver injury and have significant protective effect, and protective effect is relevant with dosage, and the high dose group effect is best; The protective effect that each dosage GDG1 injection and GDG2 injection Abensanil cause mouse liver injury all is better than Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, the diammonium glycyrrhizinate injection effect of use separately.Prompting, Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination have synergism, and remarkable effect is being arranged aspect anti-acute liver damage, the fatty liver.

Test example 3 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate associating and medication are to the effect of rat chronic hepatic injury

The animal subject healthy rat, 120, body weight 180～200g, the male and female dual-purpose is divided into 12 groups at random, 10 every group.

Monoammonium glycyrrhizinate injection: self-control, 5ml:40mg

Diammonium glycyrrhizinate injection: self-control, 5ml:150mg

The GDG1 injection: self-control, 5ml:193mg contains lycium barbarum polysaccharide 110mg (being equivalent to crude drug 2g), Radix Angelicae Sinensis polysaccharide 43mg (being equivalent to crude drug 2g), monoammonium glycyrrhizinate 40mg

Dosage sees Table 1-3.

10 of test method healthy rats, subcutaneous injection Oleum Arachidis hypogaeae semen 3ml/kg, 2 times weekly, totally 8 weeks are as the normal control group.All the other rats, subcutaneous injection 40% carbon tetrachloride (CCl ₄) peanut oil solution 3ml/kg, 2 times weekly, in totally 8 weeks, induce hepatic fibrosis; Be divided into 11 groups subsequently at random, 10 every group, be respectively model group and each administration group.After this, normal control group and model group intraperitoneal injection of saline every day 20ml/kg, every day 1 time, continuous 10 weeks; Each administration group is by table 1-3 intraperitoneal injection, every day 1 time, totally 10 weeks.Behind the last administration 24h, serum glutamic pyruvic transminase (ALT), glutamic oxaloacetic transaminase, GOT (AST) and albumin level (ALB) are measured in the postcava blood sampling; Simultaneously, get hepatic tissue and do the routine pathology histological examination.

Result of the test sees Table 1-3.Compare with the normal control group, the Serum ALT of model group, AST water mean pole significantly raise (p＜0.01), serum ALB level extremely significantly descends (p＜0.01), and histopathologic examination finds that relatively more typical hepatic fibrosis appears in the test rat, illustrates the modeling success.Compare with model group, each administration group all has protective effect to hepatic fibrosis rats, can reduce Serum ALT and AST level, and rising serum ALB level alleviates degree of hepatic fibrosis and fibrosis incidence rate; Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, diammonium glycyrrhizinate injection have significant protective effect (p＜0.05) to hepatic fibrosis rats; Each dosage GDG1 injection and GDG2 injection have extremely significant protective effect (p＜0.01, p＜0.001) to hepatic fibrosis rats.

The conclusion result of the test shows that Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination have significant protective effect to hepatic fibrosis rats, and protective effect is relevant with dosage, and the high dose group effect is best; Each dosage GDG1 injection and GDG2 injection all are better than Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, the diammonium glycyrrhizinate injection effect of use separately to the protective effect of hepatic fibrosis rats.Prompting, Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination have synergism, and remarkable effect is being arranged aspect anti-hepatic fibrosis, the chronic hepatic injury.

Table 1-3 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination are to the influence of hepatic fibrosis rats

(meansigma methods ± standard deviation, n=10)

Group	Dosage	ALT(U/L)	AST(U/L)	ALB(g/L)
Group	Dosage	ALT(U/L)	AST(U/L)	ALB(g/L)	Dosage group GDG2 parenteral solution high dose group in the dosage group GDG1 parenteral solution high dose group GDG2 parenteral solution low dose group GDG2 parenteral solution in the Normal group model group matrimony vine parenteral solution group Radix Angelicae Sinensis injection group glycosides oxalic acid list ammonium parenteral solution group diammonium glycyrrhizinate injection group GDG1 parenteral solution low dose group GDG1 parenteral solution	20ml/kg 20ml/kg 75mg/kg 75mg/kg 75mg/kg 75mg/kg 25mg/kg 50mg/kg 75mg/kg 25mg/kg 50mg/kg 75mg/kg	44.38±7.21 272.26±25.41 ^##168.37±23.15 ^172.52±23.46 ^167.47±21.50 ^153.74±22.49 ^105.56±17.02 ^ace94.43±16.34 ^bdf84.80±15.86 ^bdf102.53±17.95 ^acg92.46±16.53 ^*bdh81.07±16.71 ^*bdh	252.27±28.04 424.63±47.26 ^##330.47±35.82 ^335.74±36.17 ^32792±35.62 ^314.28±36.03 ^298.76±34.25 ^ace284.80±30.04 ^bhf272.27±29.14 ^bdf292.45±35.1 3 ^acg280.76±28.84 ^*bdg269.24±27.35 ^*bdh	37.51±7.85 25.04±5.74 ^#28.03±5.84 ^27.24±5.77 ^28.94±6.15 ^29.18±6.33 ^31.84±6.01 ^ace33.76±6.72 ^ace35.61±6.90 ^*bdf32.13±5.97 ^acg33.91±6.25 ^acg36.02±7.02 ^*bdh

Test example 4 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate associating and medication are to the effect of the chronic alcoholic liver injury of mice

Monoammonium glycyrrhizinate injection: self-control, 5ml:40mg

Diammonium glycyrrhizinate injection: self-control, 10ml:150mg

Dosage sees Table 1-4.

10 of test method healthy mices are irritated stomach and are given distilled water 12ml/kg, and every day 1 time, totally 5 weeks are as the normal control group.All the other mices are irritated stomach and give 50% ethanol 12ml/kg, every day 1 time, totally 5 weeks; Be divided into 11 groups subsequently at random, be respectively model group and each administration group.After this, normal control group and model group intraperitoneal injection of saline every day 20ml/kg, every day 1 time, continuous 8 weeks; Each administration group is by table 1-4 intraperitoneal injection, every day 1 time, totally 8 weeks.Behind the last administration 24h, serum glutamic pyruvic transminase (ALT), glutamic oxaloacetic transaminase, GOT (AST) and triglyceride (TG) level are measured in the postcava blood sampling; Simultaneously, get hepatic tissue and do the routine pathology histological examination.

Result of the test sees Table 1-4.Compare with the normal control group, the Serum ALT of model group, AST, TG level all significantly raise (p＜0.01), and histopathologic examination finds that hepatic tissue is obviously impaired, and hepatocyte fatty pathological changes, vacuolar degeneration, apoptosis etc. illustrate the modeling success.Compare with model group, each administration group all has protective effect to the chronic alcoholic liver injury of mice, can reduce Serum ALT, AST, TG level, alleviates liver tissue lesions; Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, diammonium glycyrrhizinate injection have significant protective effect (p＜0.05) to the chronic alcoholic liver injury of mice; Each dosage GDG1 injection and GDG2 injection have extremely significant protective effect (p＜0.01, p＜0.001) to the chronic alcoholic liver injury of mice.

Table 1-4 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination are to the influence of the chronic alcoholic liver injury of mice

(meansigma methods ± standard deviation, n=10)

Group	Dosage	ALT(U/L)	AST(U/L)	TG(mmol/L)
Group	Dosage	ALT(U/L)	AST(U/L)	TG(mmol/L)	Dosage group GDG2 parenteral solution high dose group in the dosage group GDG1 parenteral solution high dose group GDG2 parenteral solution low dose group GDG2 parenteral solution in the Normal group model group matrimony vine parenteral solution group Radix Angelicae Sinensis injection group ammonium glycyrrhizinate parenteral solution group diammonium glycyrrhizinate injection group GDG1 parenteral solution low dose group GDG1 parenteral solution	20ml/kg 20ml/kg 75mg/kg 75mg/kg 75mg/kg 75mg/kg 25mg/kg 50mg/kg 75mg/kg 25mg/kg 50mg/kg 75mg/kg	43.27±8.20 265.73±25.74 ^##182.43±25.34 ^179.31±20.46 ^192.27±22.65 ^183.58±21.81 ^107.73±1 9.27 ^ace96.43±18.74 ^acf82.17±17.35 ^bdf105.56±18.86 ^acg95.70±18.23 ^*ach82.72±16.75 ^*bdh	261.72±29.04 432.59±46.27 ^##377.62±36.31 ^362.45±35.94 ^384.73±37.42 ^376.49±36.70 ^314.82±34.16 ^ace299.20±28.71 ^bdf282.70±28.04 ^bdf314.21±36.05 ^acg297.27±28.46 ^*bdh281.45±27.53 ^*bdh	1.15±0.51 3.92±0.73 ^##1.93±0.50 ^1.88±0.47 ^2.22±0.53 ^2.08±0.62 ^1.44±0.36 ^ace1.33±0.35 ^acf1.27±0.18 ^bdf1.42±0.37 ^acg1.33±0.34 ^ach1.26±0.21 ^*bdh

Compare with Fructus Lycii injection group: ^aP＜0.05, ^bP＜0.01: compare with the Radix Angelicae Sinensis injection group: ^cP＜0.05, ^dP＜0.01;

The conclusion result of the test shows that Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination have significant protective effect to the chronic alcoholic liver injury of mice, and protective effect is relevant with dosage, and the high dose group effect is best; Each dosage GDG1 injection and GDG2 injection all are better than Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, the diammonium glycyrrhizinate injection effect of use separately to the protective effect of the chronic alcoholic liver injury of mice.Prompting, Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination have synergism, and remarkable effect is being arranged aspect the resisting alcoholic hepatic injury.

The effect of test example 5 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate associating and the anti-DHB of medication

Animal subject 1 age in days Beijing duck, the male and female dual-purpose.

Test sample injection acyclovir (positive controls): 0.25mg, Hubei KeYi Pharmacentic Co., Ltd.

Monoammonium glycyrrhizinate injection: self-control, 5ml:40mg

Diammonium glycyrrhizinate injection: self-control, 10ml:150mg

Dosage sees Table 1-5.

Test method 1 age in days Beijing duck foot intravenous injection DHBV-DNA positive serum, every 0.2ml infects and got blood in back 7 days, separation of serum ,-20 ℃ of preservations are to be checked.Filter out 72 of the positive ducks that infect successfully, be divided into 12 groups at random, 6 every group, be respectively model group, positive controls and each administration group.Infect back beginning in the 13rd day, model group intravenous injection every day normal saline 20ml/kg, every day 1 time, continuous 2 weeks; Positive controls intravenous injection injection acyclovir 30mg/kg, every day 1 time, continuous 2 weeks; Each administration group is by table 1-5 intravenous administration, every day 1 time, continuous 2 weeks.Respectively at before the administration, after administration the 7th day, administration the 14th day and the drug withdrawal the 3rd day, from duck lower limb shin vein haemospasia, separation of serum ,-20 ℃ of preservations are to be checked.It is clear to detect above-mentioned Sanguis Anas domestica with DHBV-DNA Dot Blot method, is worth as specimen DHBV-DNA level value with hybridization spot absorbance (OD).

Result of the test sees Table 1-5.Compare with model group, each administration group all has remarkable inhibitory action (p＜0.05, p＜0.01, p＜0.001) to duck DHBV virus.Positive control injection acyclovir has utmost point significant inhibitory effect (p＜0.001) to duck DHBV virus, but the DHBV level raises again after the drug withdrawal; Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, diammonium glycyrrhizinate injection all have significant inhibitory effect (p＜0.05) to duck DHBV virus, but the DHBV level of monoammonium glycyrrhizinate injection, diammonium glycyrrhizinate injection administration group obviously raises again after the drug withdrawal; Low dosage GDG1 injection and low dosage GDG2 injection all have significant inhibitory effect (p＜0.05) to duck DHBV virus, middle and high dosage GDG1 injection and GDG2 injection have utmost point significant inhibitory effect (p＜0.01), and the DHBV level does not have obvious rising after the drug withdrawal.

Table 1-5 Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination are to the inhibitory action of duck DHBV-DNA

(meansigma methods ± standard deviation, n=6)

Group	Dosage	Before the administration	OD ₄₉₀Value
			OD ₄₉₀Value			Administration the 7th day	Administration the 14th day	After the administration 3 days
			Dosage group GDG2 parenteral solution high dose group in the dosage group GDG1 parenteral solution high dose group GDG2 parenteral solution low dose group GDG2 parenteral solution in the model group positive controls matrimony vine parenteral solution group Radix Angelicae Sinensis injection group ammonium glycyrrhizinate parenteral solution group diammonium glycyrrhizinate injection group GDG1 parenteral solution low dose group GDG1 parenteral solution	20ml/kg 30mg/kg 75mg/kg 75mg/kg 75mg/kg 75mg/kg 50mg/kg 50mg/kg 75mg/kg 25mg/kg 50mg/kg 75mg/kg	1.63±0.06 1.64±0.05 1.63±0.04 1.62±0.07 1.62±0.05 1.63±0.05 1.61±0.06 1.63±0.07 1.64±0.04 1.64±0.06 1.62±0.05 1.63±0.04	Administration the 7th day	Administration the 14th day	After the administration 3 days	1.63±0.07 0.76±0.13 ^**1.30±0.12 ^1.31±0.13 ^1.32±0.11 ^1.29±0.12 ^1.02±0.11 ^ace0.94±0.15 ^bdf0.83±0.13 ^bdf1.01±0.12 ^acg0.92±0.13 ^bdh0.82±0.12 ^*bdh	1.64±0.07 0.73±0.15 ^**1.26±0.12 ^1.27±0.11 ^1.28±0.13 ^1.28±0.10 ^0.98±0.14 ^ace0.89±0.09 ^ace0.79±0.12 ^bdf0.97±0.12 ^acg0.90±0.12 ^acg0.79±0.14 ^*bdh	1.64±0.05 1.60±0.12 1.33±0.13 ^1.33±0.12 ^1.57±0.17 1.58±0.17 1.04±0.11 ^acf0.96±0.13 ^acf0.87±0.12 ^bdf1.04±0.11 ^ach0.97±0.10 ^bdh0.86±0.12 ^bdh

Compare with model group: ^*P＜0.05, ^*P＜0.01, ^{* *}P＜0.001;

The conclusion result of the test shows that Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination have significant inhibitory effect to duck DHBV virus, and inhibitory action is relevant with dosage, and the high dose group effect is best; Each dosage GDG1 injection and GDG2 injection all are better than Fructus Lycii injection, Radix Angelicae Sinensis injection, monoammonium glycyrrhizinate injection, the diammonium glycyrrhizinate injection effect of use separately to the inhibitory action of duck DHBV virus.During the administration, high dose group GDG1 injection and GDG2 injection are to the inhibitory action of the duck DHBV virus effect a little less than positive controls injection acyclovir, but the effect of GDG1 injection and GDG2 injection obviously is better than the effect of injection acyclovir after the drug withdrawal.Prompting, Fructus Lycii, Radix Angelicae Sinensis, monoammonium glycyrrhizinate or diammonium glycyrrhizinate drug combination have synergism, and remarkable effect is arranged aspect antiviral hepatitis, and do not have rebound phenomenon after the drug withdrawal.

Test example 6 GDG1 injection, GDG2 injection stability test

Test sample GDG1 injection: self-control, 5ml:193mg contains lycium barbarum polysaccharide 110mg (being equivalent to crude drug 2g), Radix Angelicae Sinensis polysaccharide 43mg (being equivalent to crude drug 2g), monoammonium glycyrrhizinate 40mg

Investigation project character, pH value, clarity, related substance, sign content.

Long term test is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and was placed 12 months.Respectively at 3rd month, 6 months, 9 months, 12 months, relatively after the outward appearance, test every index, with result and comparison in 0 month; Increase aseptic and pyrogen test 12 the end of month.

Placed 12 months under the condition of 25 ℃ ± 2 ℃ of result of the test temperature, relative humidity 60% ± 10%, every index has no significant change; At 12 the end of month of long term test, pyrogen, sterility test are all up to specification.

Conclusion is above-mentioned investigation result show, every index of GDG1 injection, GDG2 injection is all more stable, can long term storage, be adapted to that industry is big produces.

4, the specific embodiment

The specific embodiment of form is described in further detail foregoing of the present invention by the following examples, but this should 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.

Replacing with lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide, monoammonium glycyrrhizinate with GDG1 in following examples is the pharmaceutical composition of main effective ingredient, and replacing with lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide, diammonium glycyrrhizinate with GDG2 is the pharmaceutical composition of main effective ingredient. Embodiment 4～10In used lycium barbarum polysaccharide be Embodiment 1The preparation gained, used Radix Angelicae Sinensis polysaccharide is Embodiment 2The preparation gained, used Fructus Lycii Radix Angelicae Sinensis is carried thing altogether and is Embodiment 3The preparation gained.

The preparation of embodiment 1 lycium barbarum polysaccharide and discriminating and assay

The preparation of lycium barbarum polysaccharide

Get the Fructus Lycii medical material, add 80% alcohol reflux secondary, each 2 hours, filter, discard behind the filtrate recycling ethanol.Medicinal residues decoct with water three times, each 1 hour, filter, filtrate decompression is concentrated into relative density 1.10～1.12 (60 ℃), puts coldly, and cold preservation is put and left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, stir adding concentrated hydrochloric acid adjust pH to 1～2 down, cold preservation is put and was left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, with 4 times of volume of ethanol precipitations, after 24 hours, the leaching precipitation gets crude polysaccharides in refrigerator cold-storage.Crude polysaccharides adds the suitable quantity of water dissolving, filters, and filtrate adds 2% active carbon, be heated to 80 ℃ and be incubated 20 minutes, filter while hot, filtrate is concentrated into relative density 1.14～1.16 (60 ℃), adds 4 times of volume of ethanol precipitations, cold preservation is sucking filtration after 24 hours, precipitation is used dehydrated alcohol, acetone, and each washing of ether is once, vacuum drying below 60 ℃, promptly.Lycium barbarum polysaccharide yield by this prepared is 5～6%, and the content of polysaccharide is not less than 70%.

Prepare three batches of lycium barbarum polysaccharide respectively, yield sees Table 2-1.

The discriminating of lycium barbarum polysaccharide

Get this product 50mg, add water 5ml dissolving, as need testing solution.Other gets Fructus Lycii control medicinal material 0.5g, adds water 35ml, and heated and boiled 15 minutes is put coldly, filters, and filtrate is extracted with ethyl acetate 15ml jolting, and extracting solution is concentrated into about 1ml, makes control medicinal material solution.Each 5 μ l of above-mentioned two kinds of solution are drawn in the thin layer chromatography test, put respectively on same silica gel g thin-layer plate, and be developing solvent with ethyl acetate-chloroform-formic acid (3: 2: 1), launch, take 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.

Respectively above-mentioned three batches of lycium barbarum polysaccharide are carried out discrimination test, the result all meets the requirements.

The assay of lycium barbarum polysaccharide

The glucose 10mg that the preparation precision of standard glucose solution takes by weighing 105 ℃ of dry constant weights puts in the 100ml measuring bottle, is dissolved in water and is diluted to scale, shakes up.

Glucose standard solution 0.1,0.2,0.3,0.4,0.5,0.6 is accurately measured in the standard curve drafting, 0.7ml puts in the dry test-tube, adds water respectively and makes into 2ml, adds 5% phenol solution 1ml more respectively, shakes up, then enriching H ₂SO ₄5.0ml, fully shake up, placed 5 minutes, heating was taken out in 20 minutes in 60 ℃ of water-baths, was cooled to room temperature rapidly, made blank simultaneously, at 490nm wavelength place, measured its absorption maximum degree, the drawing standard curve, promptly.

The algoscopy precision takes by weighing this product 40mg, be dissolved in water and standardize solution in the 50ml volumetric flask, shake up, standby.Accurately measure 0.1ml, add water to 2ml, survey its trap value by the same method of bioassay standard curve.And calculating content.

Respectively above-mentioned three batches of lycium barbarum polysaccharide are carried out assay, the results are shown in Table 2-1.

Lycium barbarum polysaccharide yield by this prepared is 5～6%, and the content of polysaccharide is not less than 80%.

The assay result and the yield of table 2-1 lycium barbarum polysaccharide

Lot number	Polyoses content (%)	Medical material amount (kg)	Extract amount (g)	Yield (%)
Lot number	Polyoses content (%)	Medical material amount (kg)	Extract amount (g)	Yield (%)	1 2 3	82.52 85.70 83.31	10 10 10	580.8 517.4 552.6	5.81 5.17 5.53
On average	83.84	(55.03g/kg extract/medical material)		5.50	1 2 3	82.52 85.70 83.31	10 10 10	580.8 517.4 552.6	5.81 5.17 5.53

The preparation of embodiment 2 Radix Angelicae Sinensis polysaccharides and discriminating and assay

The preparation of Radix Angelicae Sinensis polysaccharide

Get the Radix Angelicae Sinensis medical material, add 80% alcohol reflux secondary, each 2 hours, filter, discard behind the filtrate recycling ethanol.Medicinal residues decoct with water three times, each 1 hour, filter, filtrate decompression is concentrated into relative density 1.10～1.12 (60 ℃), puts coldly, and cold preservation is put and left standstill l2 hour, centrifugal 20 minutes, discard precipitation, get supernatant, stir adding concentrated hydrochloric acid adjust pH to 1～2 down, cold preservation is put and was left standstill 12 hours, centrifugal 20 minutes, discard precipitation, get supernatant, with 4 times of volume of ethanol precipitations, after 24 hours, the leaching precipitation gets crude polysaccharides in refrigerator cold-storage.Crude polysaccharides adds the suitable quantity of water dissolving, filters, and filtrate adds 2% active carbon, be heated to 80 ℃ and be incubated 20 minutes, filter while hot, filtrate is concentrated into relative density 1.14～1.16 (60 ℃), adds 4 times of volume of ethanol precipitations, cold preservation is sucking filtration after 24 hours, precipitation is used dehydrated alcohol, acetone, and each washing of ether is once, vacuum drying below 60 ℃, promptly.Radix Angelicae Sinensis polysaccharide yield by this prepared is 1～3%, and the content of polysaccharide is not less than 70%.

Prepare three batches of Radix Angelicae Sinensis polysaccharides respectively, yield sees Table 2-2.

The discriminating of Radix Angelicae Sinensis polysaccharide

Get this product 50mg, add water 5ml dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 3g, adds petroleum ether (30～60 ℃) 30ml, and about 30 minutes of dipping and jolting filter, and filtrate volatilizes, and residue adds dehydrated alcohol 1ml makes dissolving, makes control medicinal material solution.Each 10 μ l of above-mentioned two kinds of solution are drawn in the thin layer chromatography test, put respectively on same silica gel g thin-layer plate, and be developing solvent with petroleum ether (30～60 ℃)-ethyl acetate (4: 1), launch, take 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.

Respectively above-mentioned three batches of Radix Angelicae Sinensis polysaccharides are carried out discrimination test, the result all meets the requirements.

The assay of Radix Angelicae Sinensis polysaccharide

Respectively above-mentioned three batches of Radix Angelicae Sinensis polysaccharides are carried out assay, the results are shown in Table 2-2.

Radix Angelicae Sinensis polysaccharide yield by this prepared is 1～3%, and the content of polysaccharide is not less than 80%.

The assay result and the yield of table 2-2 Radix Angelicae Sinensis polysaccharide

Lot number	Polyoses content (%)	Medical material amount (kg)	Extract amount (g)	Yield (%)
Lot number	Polyoses content (%)	Medical material amount (kg)	Extract amount (g)	Yield (%)	1 2 3	80.76 82.24 83.37	10 10 10	246.6 211.4 185.3	2.47 2.11 1.85
On average	82.12	2144g/kg (extract/medical material)		2.14	1 2 3	80.76 82.24 83.37	10 10 10	246.6 211.4 185.3	2.47 2.11 1.85

Embodiment 3 Fructus Lycii Radix Angelicae Sinensis are carried the preparation and the assay of thing altogether

The Fructus Lycii Radix Angelicae Sinensis is proposed the preparation of thing altogether

Prepare three batches of Fructus Lycii Radix Angelicae Sinensis respectively and carry thing altogether, extract yield sees Table 2-3.

The Fructus Lycii Radix Angelicae Sinensis is carried the assay of thing altogether

Respectively above-mentioned three batches of Fructus Lycii Radix Angelicae Sinensis are carried thing altogether and carry out assay, the results are shown in Table 2-3.

Putting forward the thing yield altogether by the Fructus Lycii Radix Angelicae Sinensis of this prepared is 3～4%, and the content of polysaccharide is not less than 80%.

Table 2-3 Fructus Lycii Radix Angelicae Sinensis is put forward the assay result and the yield of thing altogether

Lot number	Polyoses content (%)	Fructus Lycii+Radix Angelicae Sinensis (kg)	Extract amount (g)	Yield (%)
Lot number	Polyoses content (%)	Fructus Lycii+Radix Angelicae Sinensis (kg)	Extract amount (g)	Yield (%)	1 2 3	81.27 83.50 82.32	5+5 5+5 5+5	390.7 324.2 356.0	3.91 3.24 3.56
On average	82.36	(35.70g/kg extract/medical material)		3.57	1 2 3	81.27 83.50 82.32	5+5 5+5 5+5	390.7 324.2 356.0	3.91 3.24 3.56

The preparation of embodiment 4 GDG injection

1, prescription:

The GDG1 injection formula:

Lycium barbarum polysaccharide 110g (being equivalent to crude drug 2kg)

Radix Angelicae Sinensis polysaccharide 43g (being equivalent to crude drug 2kg)

Monoammonium glycyrrhizinate 40g

Cysteine hydrochloride 30g

Glycine 400g

Tween-80 20g

Water for injection adds to 5000ml

Prepare 1000 altogether

Annotate: main effective ingredient total content is 83.36% in the Chinese medicine total extract.

The GDG2 injection formula:

The Fructus Lycii Radix Angelicae Sinensis is carried thing 143g (being equivalent to crude drug Fructus Lycii 2kg, Radix Angelicae Sinensis 2kg) altogether

Diammonium glycyrrhizinate 150g

Water for injection adds to 5000ml

Prepare 1000 altogether

Annotate: main content of effective is 82.36% in the Chinese medicine extract.

2, concrete steps:

(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) get the water for injection of dosing amount 80%, add the Tween-80 stirring and dissolving, add lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide and monoammonium glycyrrhizinate, cysteine hydrochloride, the glycine of recipe quantity then, the heated and stirred dissolving fully, benefit adds to the full amount of water for injection;

Perhaps: the Fructus Lycii Radix Angelicae Sinensis of recipe quantity is carried the water for injection that thing and diammonium glycyrrhizinate add dosing amount 40% altogether, the heated and stirred dissolving fully, benefit adds to the full amount of water for injection;

(3) injection-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 0.45 μ m;

(6) clarity of inspection solution, the semi-finished product chemical examination;

(7) with filled with solution, sealing by fusing in glass ampule;

(8) 100 ℃ of flowing steam sterilizations 30 minutes;

(9) while hot sample being put into 0.01% methylene blue solution hunts leak;

(10) lamp inspection, finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 5 injection GDG

1, prescription;

Injection GDG1 prescription:

Monoammonium glycyrrhizinate 40g

Cysteine hydrochloride 30g

Glycine 400g

Tween-80 20g

Mannitol 200g

Sterile water for injection adds to 3000ml

Prepare 1000 altogether

Annotate: mainly containing effective component content in the Chinese medicine extract is 82.36%.

Injection GDG2 prescription:

Lycium barbarum polysaccharide 110g (being equivalent to crude drug 2kg)

Diammonium glycyrrhizinate 150g

Mannitol 200g

Sterile water for injection adds to 3000ml

Prepare 1000 altogether

2, concrete steps:

(1) vessel of at first dosing being used and antibiotic glass bottle, plugs etc. carry out aseptic process;

(2) take by weighing raw material and adjuvant according to recipe quantity;

(3) get the sterile water for injection of dosing amount 80%, add the Tween-80 stirring and dissolving, add the Fructus Lycii Radix Angelicae Sinensis then and carry thing and monoammonium glycyrrhizinate, cysteine hydrochloride, glycine altogether, the heated and stirred dissolving fully, add the dissolving of mannitol heated and stirred more fully, add sterile water for injection to full dose;

Perhaps: the lycium barbarum polysaccharide of recipe quantity, Radix Angelicae Sinensis polysaccharide and diammonium glycyrrhizinate are added the water for injection of dosing amount 40%, and the heated and stirred dissolving adds the dissolving of mannitol heated and stirred fully fully again, adds sterile water for injection to full dose;

(4) injection-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 0.22 μ m;

(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;-40 ℃ of pre-freezes 4 hours, low-temperature vacuum drying-40 ℃～0 ℃ 18 hours was warming up to 20 ℃ of vacuum dryings 4 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 6 GDG sodium chloride injections

1, prescription:

GDG1 sodium chloride injection prescription:

Lycium barbarum polysaccharide 110g (being equivalent to crude drug 2kg)

Monoammonium glycyrrhizinate 40g

Cysteine hydrochloride 30g

Glycine 400g

Tween-80 20g

Sodium chloride 900g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

GDG2 sodium chloride injection prescription:

Lycium barbarum polysaccharide 110g (being equivalent to crude drug 2kg)

Diammonium glycyrrhizinate 150g

Sodium chloride 900g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

2, concrete steps:

(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) get the water for injection of dosing amount 20%, add the Tween-80 stirring and dissolving, add the Fructus Lycii Radix Angelicae Sinensis then and carry thing and monoammonium glycyrrhizinate, cysteine hydrochloride, glycine altogether, the heated and stirred dissolving fully; Sodium chloride is complete with the water for injection dissolving of dosing amount 40%;

Perhaps: the lycium barbarum polysaccharide of recipe quantity, Radix Angelicae Sinensis polysaccharide and diammonium glycyrrhizinate are added the water for injection of dosing amount 40%, and the heated and stirred dissolving fully; Sodium chloride is complete with the water for injection dissolving of dosing amount 40%;

(3) merge above-mentioned solution, benefit adds to the full amount of water for injection;

(6) through the microporous filter membrane fine straining of 0.45 μ m;

(8) fill is in the infusion bottle of 100ml;

(9) 115 ℃ of pressure sterilizings 30 minutes;

The preparation of embodiment 7 GDG glucose injections

1, prescription:

GDG1 glucose injection prescription:

Monoammonium glycyrrhizinate 40g

Cysteine hydrochloride 30g

Glycine 400g

Tween-80 20g

Glucose 5000g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Annotate: main content of effective is 82.36% in the Chinese medicine extract.

GDG2 glucose injection prescription:

Diammonium glycyrrhizinate 150g

Glucose 5000g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Annotate: main content of effective is 82.36% in the Chinese medicine extract.

2, concrete steps:

(2) get the water for injection of dosing amount 20%, add the Tween-80 stirring and dissolving, add the Fructus Lycii Radix Angelicae Sinensis then and carry thing and monoammonium glycyrrhizinate, cysteine hydrochloride, glycine altogether, the heated and stirred dissolving fully; Glucose is complete with the water for injection dissolving of dosing amount 40%;

Perhaps: the Fructus Lycii Radix Angelicae Sinensis of recipe quantity is carried the water for injection that thing and diammonium glycyrrhizinate add dosing amount 40% altogether, and the heated and stirred dissolving fully; Glucose is complete with the water for injection dissolving of dosing amount 40%;

(6) through the microporous filter membrane fine straining of 0.45 μ m;

(8) fill is in the infusion bottle of 100ml;

(9) 115 ℃ of pressure sterilizings 30 minutes;

The preparation of embodiment 8 GDG sheets

1, prescription:

The GDG1 tablet recipe:

Lycium barbarum polysaccharide 110g (being equivalent to crude drug 2kg)

Monoammonium glycyrrhizinate 40g

Methionine 40g

Glycine 40g

Starch 50.0g

Pregelatinized Starch 40.0g

Microcrystalline Cellulose 50.0g

The 2%HPMC50% alcoholic solution is an amount of

Magnesium stearate 2.0g

Carboxymethylstach sodium 20.0g

Prepare 1000 altogether

The GDG2 tablet recipe:

Lycium barbarum polysaccharide 110g (being equivalent to crude drug 2kg)

Diammonium glycyrrhizinate 150g

Starch 50.0g

Pregelatinized Starch 50.0g

Microcrystalline Cellulose 50.0g

The 2%HPMC50% alcoholic solution is an amount of

Magnesium stearate 2.0g

Carboxymethylstach sodium 20.0g

Prepare 1000 altogether

2, concrete steps:

(1) it is standby lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide and monoammonium glycyrrhizinate (or diammonium glycyrrhizinate) to be pulverized 100 mesh sieves;

(2) take by weighing raw material and adjuvant according to recipe quantity;

(3) hypromellose 2% the aqueous solution made soluble in water is standby;

(4) with lycium barbarum polysaccharide, Radix Angelicae Sinensis polysaccharide, monoammonium glycyrrhizinate (or diammonium glycyrrhizinate), starch, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, add aminoacid according to the prescription needs, it is an amount of to add the 2%HPMC50% alcoholic solution, stirs, and makes suitable soft material;

(5) cross 20 mesh sieve system granules; Granule is dried under 60 ℃ condition;

(6) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously;

(7) sampling, the semi-finished product chemical examination;

(8) the sheet weight sheet of determining according to chemical examination;

(9) finished product is examined entirely, the packing warehouse-in.

The capsular preparation of embodiment 9 GDG

1, prescription:

GDG1 capsule prescription:

Monoammonium glycyrrhizinate 40g

Methionine 40g

Glycine 40g

Starch 50.0g

Pregelatinized Starch 40.0g

Microcrystalline Cellulose 40.0g

The 2%HPMC50% alcoholic solution is an amount of

Magnesium stearate 1.0g

Prepare 1000 altogether

Annotate: main content of effective is 82.26% in the Chinese medicine extract.

GDG2 capsule prescription:

Diammonium glycyrrhizinate 150g

Starch 50.0g

Pregelatinized Starch 50.0g

Microcrystalline Cellulose 40.0g

The 2%HPMC50% alcoholic solution is an amount of

Magnesium stearate 2.0g

Prepare 1000 altogether

Annotate: main content of effective is 82.26% in the Chinese medicine extract.

2, concrete steps:

(1) the Fructus Lycii Radix Angelicae Sinensis being carried altogether thing and monoammonium glycyrrhizinate (or diammonium glycyrrhizinate), to pulverize 100 mesh sieves standby;

(2) take by weighing raw material and adjuvant according to recipe quantity;

(3) hypromellose 2% the aqueous solution made soluble in water is standby;

(4) the Fructus Lycii Radix Angelicae Sinensis is carried altogether thing, monoammonium glycyrrhizinate (or diammonium glycyrrhizinate), starch, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, add aminoacid according to the prescription needs, it is an amount of to add the 2%HPMC50% alcoholic solution, stirs, and makes 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 determining according to chemical examination incapsulates;

(10) finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 10 GDG

1, prescription:

GDG1 granule prescription:

Monoammonium glycyrrhizinate 40g

Methionine 40g

Glycine 40g

Icing Sugar 1250.0g

Correctives is an amount of

The 2%HPMC50% alcoholic solution is an amount of

Prepare 1000 bags altogether

Annotate: main content of effective is 82.26% in the Chinese medicine extract.

GDG2 granule prescription:

Diammonium glycyrrhizinate 150g

Icing Sugar 1200.0g

Correctives is an amount of

The 2%HPMC50% alcoholic solution is an amount of

Prepare 1000 bags altogether

Annotate: main content of effective is 82.26% in the Chinese medicine extract.

2, concrete steps:

(1) it is standby sucrose to be pulverized 100 mesh sieves, and the Fructus Lycii Radix Angelicae Sinensis is carried thing and monoammonium glycyrrhizinate (or diammonium glycyrrhizinate) altogether, and to pulverize 100 mesh sieves standby;

(2) take by weighing raw material and adjuvant according to recipe quantity;

(3) the Fructus Lycii Radix Angelicae Sinensis is carried altogether the method mix homogeneously that thing, monoammonium glycyrrhizinate (or diammonium glycyrrhizinate) and Icing Sugar, correctives progressively increase with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes 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 determined loading amount in the semi-finished product chemical examination granule;

(8) packing; Finished product is examined entirely, the packing warehouse-in.

Claims

1, a kind of pharmaceutical composition is characterized in that, said composition is mainly made by following bulk drugs: 1～50 part of 50～1000 parts of Fructus Lycii, 50～1000 parts of Radix Angelicae Sinensis, glycyrrhizic acid or its pharmaceutically acceptable salt.

2, pharmaceutical composition as claimed in claim 1 is characterized in that, the weight portion of each crude drug is: 2～30 parts of 100～500 parts of Fructus Lycii, 100～500 parts of Radix Angelicae Sinensis, glycyrrhizic acid or its pharmaceutically acceptable salts.

3, pharmaceutical composition as claimed in claim 2 is characterized in that, the weight portion of each crude drug is: 4～15 parts of 200 parts of Fructus Lycii, 200 parts of Radix Angelicae Sinensis, glycyrrhizic acid or its pharmaceutically acceptable salts.

4, as the described arbitrary preparation of drug combination method of claim 1～3, it is characterized in that, described Fructus Lycii, Radix Angelicae Sinensis can with The suitable solvent and method separately or mixed extraction processing obtain extract, total extract is processed into clinically arbitrary or pharmaceutically acceptable dosage form with glycyrrhizic acid or its pharmaceutically acceptable salt and mixing acceptable accessories again.

5, preparation of drug combination method as claimed in claim 4 is characterized in that, main effective ingredient contained in the described total extract is lycium barbarum polysaccharide and Radix Angelicae Sinensis polysaccharide, and the total content of contained main effective ingredient is not less than 50% in the total extract.

6, pharmaceutical composition as claimed in claim 1 is characterized in that, said composition also can be made by following bulk drugs: 1～50 part of 2.5～50 parts of lycium barbarum polysaccharide, 1～20 part of Radix Angelicae Sinensis polysaccharide, glycyrrhizic acid or its pharmaceutically acceptable salt.

7, pharmaceutical composition as claimed in claim 6, its spy is that the weight portion of each crude drug is: 2～30 parts of 5～25 parts of lycium barbarum polysaccharide, 2～10 parts of Radix Angelicae Sinensis polysaccharides, glycyrrhizic acid or its pharmaceutically acceptable salts.

8, as claim 6,7 described arbitrary pharmaceutical compositions, it is characterized in that the content of polysaccharide is not less than 30% in the described lycium barbarum polysaccharide, the content of polysaccharide is not less than 30% in the Radix Angelicae Sinensis polysaccharide.

9, as claim 1,2,3,6,7 described arbitrary pharmaceutical compositions, it is characterized in that described glycyrrhizic acid pharmaceutically acceptable salt is mono-ammonium, di-ammonium salts.

As claim 1,2,3,6,7 described arbitrary pharmaceutical compositions, it is characterized in that 10, said composition can be made clinically arbitrary or pharmaceutically acceptable dosage form with mixing acceptable accessories.