CN102058825B - Traditional Chinese medicinal composition for treating hepatitis and preparation method thereof - Google Patents

Abstract

The invention discloses a traditional Chinese medicinal composition for treating hepatitis and a preparation method thereof. The traditional Chinese medicinal composition for treating the hepatitis is prepared from the following raw materials: pseudo-ginseng root, golden thread, baical skullcap root, amur corktree bark, rhubarb, spreading hedyotis herb, snake gall, borneol, calculus bovis factitius, aritificial musk, curcuma aromatica and red yeast. The traditional Chinese medicinal composition for treating the hepatitis can be prepared into multiple common formulations for oral administration. The traditional Chinese medicinal preparation treats the hepatitis by clearing heat, detoxicating, removing blood stasis, eliminating stagnation, invigorating blood circulation, dissolving stasis, detoxicating and normalizing gallbladder, has the obvious effects of improving liver function and inhibiting liver injury and hepatitis virus, addresses both symptoms and root causes, requires a short treatment period, realizes a low relapse rate, and has the obvious pharmacological action of protecting the liver and reducing transaminase and serum bilirubin.

Description

A kind of Chinese medicine composition of treating hepatitis and preparation method thereof

Technical field

The present invention relates to a kind of Chinese patent medicine and preparation method thereof, particularly a kind of Chinese medicine composition of treating hepatitis and preparation method thereof.

Background technology

Hepatopathy, particularly hepatitis B are one of modal infectious disease in the world; According to interrelated data; Annual because hepatopathy causes nearly 1,000,000 people dead, China is hepatopathy country occurred frequently, has 3 approximately at present; 0,000,000 chronic hepatitis B patient and 1.2 hundred million hepatitis B virus carrierss account for more than 10% of country's total population respectively.Hepatopathys such as viral hepatitis, hepatic fibrosis, fatty liver, alcoholic liver pathological changes, medicamentous liver lesion and hepatocarcinoma more and more become the principal disease that threatens compatriots healthy in recent years.

It is a chronic allergy course of damage that hepatitis virus entering human body causes hepatic injury, causes hepatomegaly, causes the hepatocyte inflammation.Because the exudate of hepatocyte inflammation, the hepatocyte epimatrix increases, and makes a large amount of hypertrophy in liver plasma membrane surface, the parcel surface of hepatocytes; Cell wall thickens, and " permeability " descends, dysbolismus, the further enlargement of hepatocyte; Make the blood flow extruding between cell and the cell, form the dry ischemic stasis of blood and stagnate, hepatic necrosis and fibrosis, non-viable non-apoptotic cell and fibroplasia alternate; Form vicious cycle, cause liver blood stream to block, portal vein is pathological changes (being that portal pressure increases, ascites splenomegaly or hemorrhage etc.).The hepatitis disease directly influences people's life, family and society, interpersonal getting along amiably and peacefully.And traditional Western medicine can't be cured, and relapse rate, bounce-back rate are high, even medication also can only suppress virus, can not eliminate virus, bounce-back at once after the drug withdrawal, hepatitis recurrence.

Clinically, the medicine of western medical treatment hepatitis is mainly IFN-and lamivudine.The clinical studies show IFN-is concerning producing the degree that continues can to alleviate the hepatitis C patients that virusology replys its hepatic fibrosis after treatment, but some people is insensitive to interferon, and it is high to use the back relapse rate, and side effect is big, costs an arm and a leg.Interferon and ribavirin Combined application can be removed hepatitis C viruss more than half, and antiviral therapy also can improve the hepatic fibrosis process, and possibly reverse liver cirrhosis.IFN-treatment hepatitis B also can improve hepatic fibrosis, and the index of hepatic fibrosis obviously descends.

Lamivudine can effectively suppress duplicating of HBV DNA, and the serum conversion of part patient HBeAg/anti HBe is arranged.Treating 2 years heptic fibrosis has alleviating in various degree, or delays the process of hepatic fibrosis, but the main limitation of lamivudine is variation, and the incidence rate of 1 year and 5 years is respectively 15～32% and 67～69%.After variation, defective such as develop immunity to drugs, Histological change may increase the weight of.

In recent years, the research of Chinese medicine hepatitis disease has obtained bigger achievement, also demonstrates comparatively remarkable advantages.Can it be belonged to sick categories such as " hypochondriac pain ", " yellow cellulitis ", " tympanites " in conjunction with clinical manifestation, in addition also can be with reference to diseases such as " mausoleum is long-pending ", " addiction blood ", " gathering ".Traditional Chinese medical theory thinks that the formation of hepatopathy is also closely related with " positive QI-insufficiency ".Initial stage liver network blocks, and qi depression to blood stasis continues that then liver disease affecting spleen, deficiency-weakness of spleen-QI, and no resource of generating and transforming QI and blood on the one hand, positive QI-insufficiency, pathogen is prone to crouch, and increases the weight of blood stasis; On the other hand, qi as the commander of blood, the deficiency of vital energy are then agitated unable, and blood is capable unsmooth and living in the blood stasis.In treatment, be that master, supplementing QI and nourishing YIN are auxilliary with the blood circulation promoting and blood stasis dispelling, and combine the Therapeutic Principle of determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs that blood circulation promoting and blood stasis dispelling, strengthening the body resistance are the basic method of treatment of Chinese medicine hepatitis.

For example: publication number is that the Chinese invention patent application of CN101524512 discloses a kind of Chinese medicine preparation of treating hepatitis and preparation method thereof, the primary raw material medicine and the weight proportion of this Chinese medicine preparation: Radix Aucklandiae (Radix Vladimiriae) 6-100 part, Radix Isatidis 9-200 part; Rhizoma Curcumae 8-150 part; Cortex Magnoliae Officinalis 8-150 part, Herba Artemisiae Scopariae 8-150 part, Herba Achilleae 7-120 part; Rhizoma Cyperi 9-200 part, Semen Litchi 8-150 part.Method for preparing: medical material is cleaned, and dries to pulverize, soak, and secondary decoction filtrating merges, and gets extract, is condensed into thick paste and pulverizes, and gets medicated powder; Uniform mixing medicated powder is added appropriate amount of auxiliary materials, process capsule, tablet, granule or drop pill with common process; Publication number is that the Chinese invention patent application of CN101513488 discloses a kind of Chinese medicine composition that is used to treat hepatitis, changes the parts by weight of the crude drug of Chinese medicine composition: Radix Astragali 10-25 part, Rhizoma Atractylodis Macrocephalae 3-10 part, purple Radix Codonopsis 8-25 part; Rhizoma Polygoni Cuspidati 8-15 part, Cortex Phellodendri (parched) 3-9 part, Herba Epimedii 3-10 part, Cortex Moutan 3-10 part; Herba Portulacae Grandiflorae 6-20 part, Fructus Aurantii 3-9 part, Endothelium Corneum Gigeriae Galli 3-10 part, Radix Bupleuri 3-10 part; Radix Glycyrrhizae 3-6 part, Rhizoma Smilacis Glabrae 10-30 part, Radix Codonopsis 4-8 part; Fructus Schisandrae Chinensis 1-5 part, Herba Hedyotidis Diffusae 7-13 part, Radix Isatidis 3-7 part; Herba Hyperici Japonici 3-7 part is ground into powder and bee product 8-20 part after concocting, be hybridly prepared into graininess or pill, capsule, tablet, injection, cream slurry agent or oral liquid; For example publication number is that the application for a patent for invention of CN101485753 discloses a kind of Chinese medicine of treating hepatitis B and preparation method thereof again, and this Chinese medicine is made up of the following weight proportion raw material: giant knotweed total glycoside 0.2～0.4 weight portion, Herba Hedyotidis Diffusae 10～14 weight portions, Radix Salviae Miltiorrhizae 6～10 weight portions, Herba Lysimachiae 6～10 weight portions, Radix Scutellariae extract 0.8～1.2 weight portion, Fructus Schisandrae Chinensis 4～8 weight portions.This Chinese medicine through extract, concentrate, processing technique such as refining, drying processes pill, tablet, capsule, granule, soft capsule, drop pill and oral liquid, has heat-clearing and toxic substances removing, liver-smoothing, qi-regulating, the effect of eliminating blood stasis and smoothing collaterals.For example publication number is that the application for a patent for invention of CN101474254 discloses a kind of Chinese medicine composition and method for preparing that has soothing liver and strengthening spleen, sets upright the treatment chronic hepatitis B of the effect of invigorating blood circulation again; This Chinese medicine composition is processed by following materials based on weight: 100～500 parts of Radix Bupleuri; 50～300 parts of Ganodermas; 100～500 parts of Radix Salviae Miltiorrhizaes, 100～500 parts of Fructus Schisandrae Chinensis.Its preparation method comprises the steps: 1) take by weighing raw material by weight; 2) with Radix Bupleuri be ground into slightly, fine powder half and half, Ganoderma, Fructus Schisandrae Chinensis and Radix Salviae Miltiorrhizae are broken, 3) in Radix Bupleuri coarse powder and Ganoderma, add ethanol, reflux, extract,, filtration, simmer down to thick paste; 4) add ethanol at Fructus Schisandrae Chinensis, Radix Salviae Miltiorrhizae, reflux, extract, is filtered the simmer down to thick paste; 5) thick paste merges, and with second half Radix Bupleuri fine powder mixing, drying is ground into fine powder, and mixing is processed described Chinese medicine composition.

Though the Chinese medicine research that is used to treat and prevents hepatitis be widely used, the Chinese medicine effect curative effect of treatment hepatitis disease is not remarkable at present, acts on singlely, specific aim is relatively poor, treatment cycle is long, the relapse rate height can not treating both the principal and secondary aspects of a disease.

Summary of the invention

Primary and foremost purpose of the present invention is to the problem that above-mentioned prior art exists a kind of Chinese medicine composition that is used to treat hepatitis and preparation method thereof to be provided, and said composition is to the cause of disease and the pathogenesis of hepatitis, the mutual synergism of the active component after utilizing plurality of Chinese by fermentation; Through heat-clearing and toxic substances removing, blood stasis-eliminating and stagnation-dissipating, blood circulation promoting and blood stasis dispelling, detoxifcation function of gallbladder promoting; The effect of treatment hepatitis can improve the hepatic pathology reaction, antitoxin hepatoprotective; Promoting tissue regeneration by removing blood stasis promotes the reparation of liver organization structure, and evident in efficacy.

For realizing the object of the invention; One aspect of the present invention provides a kind of treatment hepatitis Chinese medicine composition, mainly comprises following raw material: Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae, Fel Serpentis, Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus, Radix Curcumae, Monas cuspurpureus Went.

Wherein, the weight portion proportioning of the Chinese medicine composition raw material of described treatment hepatitis is: Radix Notoginseng 80-180, Rhizoma Coptidis 30-100, Radix Scutellariae 30-120, Cortex Phellodendri 20-100, Radix Et Rhizoma Rhei 20-100, Herba Hedyotidis Diffusae 20-100, Fel Serpentis 5-20, Borneolum Syntheticum 1-50, artificial Calculus Bovis 1-30, artificial Moschus 1-20, Radix Curcumae 1-45, Monas cuspurpureus Went 20-60.

Particularly, the weight portion proportioning of said raw material is: Radix Notoginseng 100-160, Rhizoma Coptidis 30-85, Radix Scutellariae 40-100, Cortex Phellodendri 20-90, Radix Et Rhizoma Rhei 20-80, Herba Hedyotidis Diffusae 20-80, Fel Serpentis 3-20, Borneolum Syntheticum 2-40, artificial Calculus Bovis 3-20, artificial Moschus 2-20, Radix Curcumae 2-30, Monas cuspurpureus Went 30-50.

The Chinese medicine composition of treatment hepatitis of the present invention selects Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Fel Serpentis, artificial Calculus Bovis, artificial Moschus, Radix Curcumae to make up, and is prepared from heat-clearing and toxic substances removing, blood stasis-eliminating and stagnation-dissipating through red koji fermentation.These Chinese crude drug combinations are used, utilized biofermentation technique, make that the active component in each medical material produces synergism; Mutual enhancement protects the liver, the effect of hepatoprotective; Thereby human body immunity improving power is regulated and enhances human body metabolism function, makes by the liver organization of virus damage to obtain repairing; Not only taking stopgap measures but also effect a permanent cure aspect the treatment hepatopathy, reach treating both the principal and secondary aspects of a disease.

Wherein, medical instrument such as Radix Notoginseng, Rhizoma Coptidis has eliminating stagnation blood stasis dispelling effect; The artificial Moschus can promoting the circulation of QI and blood and powder detoxifcation, and the artificial Calculus Bovis has clear away heart-fire cool liver and out-of-the-way dirty detoxifcation, and the present invention is used to treat the acute and chronic hepatitis that belongs to syndrome of dampness-heat of liver and gallbladder and syndrome of static blood blocking collaterals.

Radix Notoginseng is claimed Radix Notoginseng, Yunnan seven, Radix Notoginseng, Radix Notoginseng again, is the dry root of panax araliaceae plant.Warm in nature, sweet in the mouth, little hardship is returned liver, stomach warp.Has the dissipating blood stasis hemostasis, subduing swelling and relieving pain.Be used for spitting of blood, spit blood, epistaxis is had blood in stool, metrorrhagia, traumatic hemorrhage, breast ventral spine pain, tumbling and swelling.The active component that mainly contains multiple dammarane type four-ring triterpenoid Saponin in the Radix Notoginseng.Like arasaponin A, arasaponin B, generate ruscogenin A after the two hydrolysis respectively, ruscogenin B and a part glucose; Also contain the ginsenoside-Rb1 ,-Rb2 ,-Rd ,-Re ,-Rg1, Herb Gynostemmae Pentaphylli glycoside, dencichine (being dencichine), sanchinan-A, B and multiple human body with anastalsis must aminoacid (like glutamic acid, arginine, lysine, leucine etc.).

Modern pharmacological research shows that Radix Notoginseng can improve the immunocompetence of body, can significantly improve the phagocytic rate and the phagocytic index of Turnover of Mouse Peritoneal Macrophages.Wherein, sanchinan-A can obviously reduce natural killer cell (NKC) activity, and inhibitory action was strengthened when drug dose strengthened.Can obviously promote natural killer cell (NKC) activity during the Polysaccharide B low concentration, increase facilitation with concentration and weaken.Polysaccharide A makes serum lysozyme content increase when 25mg/kg, and other dosage does not have influence; Polysaccharide B also has facilitation to lysozyme.Polysaccharide A can make the peritoneal exudate cells lysozyme content increase when 5mg/kg, and endocellular enzyme content is significantly increased, and enzyme content is increased, and high dose does not then have influence.Two kinds of polysaccharide all have inhibitory action to the mice ABC, and the inhibitory action of Polysaccharide A is strengthened with the increase of dosage, and Polysaccharide B inhibitory action when the above dosage of 25mg/kg is plateau phenomenon.Two kinds of polysaccharide antagonists of Radix Notoginseng secretory cell all has obvious inhibitory action.Two kinds of polysaccharide form cell (PFC) to hemolysis plaque also all has obvious inhibitory action.

Radix Notoginseng total arasaponins (PNS) can also significantly improve the effect of pulmonary alveolar macrophage phagocytic rate, gives Wistar rats by intraperitoneal injection Radix Notoginseng total arasaponins, and the result shows that administration group pulmonary alveolar macrophage phagocytic rate significantly improves, and the blood total white blood cells improves obviously after the administration.

Radix Notoginseng also has antiinflammatory action, and to the rat oral gavage Radix Notoginseng total arasaponins of Ovum Gallus domesticus album property pedal swelling, foot swelling has the obvious suppression effect to the total Saponin of presentation of results Radix Notoginseng fibrous root to rat Ovum Gallus domesticus album property.

Radix Notoginseng extract can improve the body hepatic glycogen, and normal mouse was irritated the stomach Radix Notoginseng extract 15 days and 25 days, and hepatic glycogen improves 80.8% and 71% respectively.The presentation of results Radix Notoginseng extract can promote mice to utilize exogenous glucose to synthesize hepatic glycogen, and most glycogen granulees are thick full in the hepatocyte of the mice of administration Radix Notoginseng extract.

Rhizoma Coptidis claims that again Coptis Teeta Wall, refined company, Rhizoma Coptidis, flavor connect, Rhizoma Coptidis, is the dry rhizome of ranunculaceae plant Rhizoma Coptidis, Coptis deltoidea C.Y.Cheng et Hsiao or Coptis Teeta Wall.Bitter in the mouth cold in nature, GUIXIN, spleen, stomach, liver, gallbladder, large intestine channel.Has heat clearing and damp drying, eliminating fire and detoxication.Be used to treat the hyperpyrexia that the calentura heresy is gone into heart channel; Irritated; Delirium or the absurd row of intenseness of heat forcing blood tell nosebleed; Damp and hot feeling of fullness, the vomiting acid regurgitation, dysentery, jaundice, unconsciousness due to high fever, hyperactivity of heart-fire, dysphoria and insomnia, heat in blood is told nosebleed, conjunctival congestion, the carbuncle furuncle is quenched one's thirst in toothache; External treatment eczema, eczema, auditory meatus is suppurated.The kind clear part of the body cavity above the diaphragm housing the heart and lungs of Rhizoma Coptidis (processed with wine) is burning hot.Be used for conjunctival congestion, aphtha.Mainly contain alkaloids such as berberine, coptisine, epiberberine, berberrubine, jateorhizine, magnoflorine, 13-methyl-.psi.-coptisine., palmatine, Columbamine in the Rhizoma Coptidis, also contain compositions such as obacunone, ferulic acid, obakulactone.

Modern pharmacological research shows that Rhizoma Coptidis has antibiotic, antifungic action, antivirus action, antiinflammatory and diarrhea effect etc.The Rhizoma Coptidis decoct all has inhibitory action to influenza virus PR8 strain, influenza A virus 56-S8 strain, A-prime virus FM1 strain, Influenza B virus Lee strain, interior type influenza virus 1233 strains; Hepatitis B virus DNA there is inhibitory action.

Radix Scutellariae is the dry root of labiate Radix Scutellariae, with relieve inflammation or internal heat, yin nourishing, to relieve internal heat be main, feeble QI; Bitter in the mouth, cold in nature, return lung, gallbladder, spleen, large intestine, small intestine meridian; Has heat clearing and damp drying, eliminating fire and detoxication, hemostasis; Antiabortive effect is mainly used in diseases such as treatment epidemic febrile disease, upper respiratory tract infection, cough due to lung-heat, damp and hot jaundice, pneumonia, dysentery, hemoptysis, conjunctival congestion, frequent fetal movement, hypertension, carbuncle furuncle.

The chemical constituent that Radix Scutellariae contains mainly is a flavone compound; Mainly contain baicaligenin, baicalin, wogonin, wogonoside, neobaicalein, oroxylin A, skullcapflavone etc., also contain 1-Phenylethanone., Palmic acid, oleic acid, proline, benzoic acid, baicalinase, cupreol, campesterol and stigmasterol etc.Radix Scutellariae has antiinflammatory, antiallergic action, antimicrobial effect, blood pressure lowering, diuresis, analgesic, spasmolytic and sedation.The clinical practice of Radix Scutellariae is antibiotic not worse than Rhizoma Coptidis, and does not develop immunity to drugs.

Cortex Phellodendri is the dry bark of rutaceae wampee or Cortex Phellodendri, claims Cortex Phellodendri, Cortex Phellodendri, bark of a cork tree wood again.Cortex Phellodendri is cold in nature, and bitter in the mouth is returned kidney, urinary bladder channel, has heat clearing and damp drying, and pathogenic fire purging removes steams, and the effect of skin ulcer is treated in detoxifcation, is used to treat damp-heat dysentery, jaundice, leukorrhagia, pyretic stranguria, beriberi, hectic fever due to YIN-deficiency consumptive fever, night sweat, seminal emission, sore swollen toxin, eczema pruritus.The stir-baked CORTEX PHELLODENDRI with salt solution nourishing YIN to lower pathogenic fire.Be used for hyperactivity of fire caused by deficiency of YIN, the night sweat hectic fever due to YIN-deficiency.

Cortex Phellodendri contains following chemical constituent: alkaloids such as berberine, jateorhizine, magnoflorine, phellodendrine, berberrubine, candicine, palmatine, candicine, guanidine, Dauricine; Other contains obacunone, obakulactone, Dictamnolide, obacunonic acid, the acid of blue or green fluorescent, 7-dehydrogenation stigmasterol, stigmasterol, cupreol, campesterol, amurensin, amurensin, phellatin, Dictamnolide, 24-methylene basic ring jackfruit alcohol, Fici hispidae pure-B, phellavin hyperin and volatile oil.

Pharmacological research shows that Cortex Phellodendri has (1) antibacterial action, and its antibiotic effective ingredient is a berberine.Cortex Phellodendri is all effective to staphylococcus aureus, streptococcus pneumoniae, diphtheria corynebacterium, Streptococcus viridans, dysentery bacterium etc.(2) hypotensive effect, hypotensive effect is remarkable and lasting, so blood pressure lowering possibly be a central.(3) antitussive effect, antiinflammatory and antiulcer effect.(4) effect of raise immunity.The Cortex Phellodendri clinical practice is in sick rash such as treatment epidemic cerebrospinal meningitis, bacillary dysentery, pneumonia, pulmonary tuberculosis, liver cirrhosis, chronic hepatitis, polarity conjunctivitis, chronic suppurative otitis medias.

Fel Serpentis is the interior liquid of gallbladder of Colubridae animal zaocys dhumnades or other kinds Serpentis, cool in nature, sweet in the mouth, little hardship.Have heat-clearing and toxic substances removing, the antispasmodic effect of reducing phlegm is mainly used in infantile pneumonia, pertussis, bronchitis, cough phlegm dyspnea, expectorant febrile convulsion, acute rheumatic arthritis.

Fel Serpentis is precious Chinese medicine, has fabulous medical value, and it can be searched, and wind dries, refrigerantly makes eye bright, relieving cough and resolving phlegm.Be applied to treat rheumatic arthritis, eye red order paste, cough ant phlegm, infantile convulsion, hemiplegia, hemorrhoid redness, various keratopathy etc. clinically, good efficacy is all arranged, among the peoplely eat traditional food therapy that Fel Serpentis is controlled gastropathy in addition.

The artificial Calculus Bovis is the succedaneum of natural Calculus Bovis, and main component is bilirubin, cholic acid, cholesterol, inorganic salt etc., and the artificial Calculus Bovis is cool in nature, sweet in the mouth, GUIXIN, Liver Channel.Have and clear away heart-fire, eliminating phlegm is had one's ideas straightened out, cool liver, and endogenous wind stopping, the antidotal effect is mainly used in the calentura coma, middle wind-phlegm fan, infantile convulsion is twitched, and epilepsy is gone mad, laryngopharynx swelling and pain, aphtha of the mouth and tongue, carbuncle furuncle.

The artificial Calculus Bovis is that the chemical constituent human configuration according to natural Calculus Bovis forms; Wherein mainly contain bilirubin, bile acid (comprising cholic acid), deoxycholic acid, bile salt, cholesterol, ergosterol, fatty acid, lecithin, vitamin D, inorganic elements calcium, sodium, ferrum; Potassium; Copper, magnesium, phosphorus etc. and several amino acids.

Pharmacological research shows that Calculus Bovis has refrigeration function, and the composition of its refrigeration function mainly is a taurine; Calculus Bovis has the effect that brings high blood pressure down, and the chemical constituent that has hypotensive effect in the Calculus Bovis mainly contains: bilirubin, cholic acid, cholates such as deoxycholic acid (particularly calcium salt); Calculus Bovis has the effect that impels blood rbc and hematochrome to increase; Calculus Bovis also has antiinflammatory action, the mouse peritoneal of ear's inflammation injection Calculus Bovis suspension due to the xylol, and every day 1 time, for three days on end, the result shows that Calculus Bovis can significantly suppress the effect of xylene induced mice ear inflammation (P＜0.01).The artificial Calculus Bovis also has identical effect; Calculus Bovis has infection, antibiotic, antiviral effect, experiment showed, the inhibition index amount height of the anti-encephalitis b virus of Calculus Bovis mesobilirubin, and deoxycholic acid and Hyodeoxycholic Acid take second place, and cholic acid is lower; The artificial Calculus Bovis can improve phagocytic percentage and phagocytic index, points out 2 kinds of artificial Calculus Boviss that apparent the effect that improves phagocytic function is all arranged, and this possibly be one of its treatment infantile hyperpyrexia convulsions, antiinflammatory, anti-infective basic role.

The Moschus another name is former Moschus, fragrant umbilicus, young grass, fragrant, the smelly son of Moschus moschiferous umbilicus, is the dry secretions in the ripe male body note capsule of animal in deer family woods Moschus moschiferous, horse Moschus moschiferous or former Moschus moschiferous.Moschus is warm in nature, acrid in the mouth, GUIXIN, spleen channel.Have the refreshment of having one's ideas straightened out, promoting blood circulation to restore menstrual flow, the effect of reducing swelling and alleviating pain is mainly used in the calentura coma, the apoplexy syncope due to accumulation of phlegm, stagnation of QI sudden syncope, the attacked by pestiferous factors stupor, amenorrhea ， WEIJIA, the difficult labour stillborn fetus, trusted subordinate's sudden pain, the carbuncle scrofula, laryngopharynx swelling and pain falls and pounces on the pain of injury, and arthralgia pain is numb.

Contain a large amount of moisture in the Moschus; Its main functional component is muscone, muscopyridine, hydroxyl muscopyridine A; Macromole cyclic ketones, cholesterol, androgen, cholesterol ester, crude fibre, fatty acid, nitrogen-containing compounds such as hydroxyl muscopyridine B (wherein contain ammonium carbonate, the ammonia in the ammonium salt, carbamide; Amino acid nitrogen, total nitrogen are 9.15%).Natural Moschus's Main Ingredients and Appearance is left-handed muscone, 3-methyl cyclotyidecanone, cyclopentadecanone, cyclotetradecanone, muscopyridine, Moschus pyrans, the 3-methylcyclopentadecanol with the effect of invigorating blood circulation of having one's ideas straightened out.11 kinds of natural cortisone hormones with antiinflammatory action; Allantoin with detumescence effect, 5 kinds of fatty alcohol sulfates with cardiotonic and similar also have 3 kinds of antiinflammatory polypeptide As 1 of being made up of a plurality of aminoacid; A2; A3, wherein the molecular weight of A1 antiinflammatory polypeptide is approximately 1000, and its antiphlogistic effects is several times of hydrocortisone.The molecular weight of A2 antiinflammatory polypeptide is approximately 6000, and its antiphlogistic effects is that the molecular weight of 40 times of .A3 antiinflammatory polypeptide of hydrocortisone is approximately 200000.Its antiphlogistic effects is more remarkable.

The Main Ingredients and Appearance of synthetic Moschus has only added in the natural Moschus content except that left-handed muscone higher; Similar with natural Moschus's relevant composition; Be prone to the cortisone hormones of synthetic and the more significant 3 kinds of synthetic of antiphlogistic effects, androgen mainly be 5 β-, 5 α-; Δ-4 three kind of parent nucleus type (comprising an Astenile) total content is about 0.9%-1.5%, more can not add molecular weight more greatly and at present still can't synthetic antiinflammatory polypeptide.

Modern pharmacological research shows that Moschus except central nervous system, respiratory system and blood circulation are had the important effect, also has antibiotic, antiinflammatory action, and the diluent of musk tincture can suppress escherichia coli and staphylococcus aureus in vitro.To the rat arthritis that is caused by the antigen of mycobacterium injection, its antiinflammation is better than other ketone; Musk water-soluble albumen has potentiation to humoral immunization and cellular immunization.Laboratory observation produces antibody to Moschus to lumbar injection sheep red blood cell (SRBC) immune mouse.Moschus does not have the immune induction effect, but in the presence of the antigen sheep red blood cell (SRBC), Moschus can make the experiment mice spleen obviously increase; Moschus also has antitumor action; Moschus has destruction to the animal cancerous cell that exsomatizes, and the animal tumor cells of tissues is breathed has obvious inhibitory action, and Moschus or muscone are to the mice ehrlich carcinoma; The Cellular respiration suppression ratio of S37 and S180 all is higher than the normal mouse suppression ratio.The artificial Moschus also has natural Moschus's pharmacological function.

The another name of Radix Curcumae is radix curcumae, white silk Radix Curcumae etc., is the dried root of zingiberaceous plant RADIX CURCUMAE, Rhizoma Curcumae Longae, Guangxi zedoary or Rhizoma Curcumae.Cold in nature, acrid in the mouth, hardship are returned liver, the heart, lung meridian.Have regulating qi to disperse stagnation, heart fire-clearing upset-relieving, the effect of promoting the function of the gallbladder to alleviate jaundice is mainly used in the amenorrhea dysmenorrhea, chest and abdomen swelling and pain, twinge, the calentura coma, epilepsy is gone mad, the jaundice dark coloured urine.Mainly contain curcumin chemical compounds in the Radix Curcumae: curcumin, demethoxycurcumin, bisdemethoxycurcumin, bisdemethoxycurcumin; Volatilization oil base main component has turmerone, fragrance-turmerone, big Mang cattle ketone, terpinene, curcumene, fragrance-curcumene, Herba chenopodii art diketone, curcumenol, cineole, Flos Caryophylli alkene, limonene, linalool, australene, nopinene, lauro lene, reaches isoborneol etc.

Modern pharmacological research shows that Radix Curcumae can regulate the humoral immunization of toxic hepatitis mice; Effect with immunosuppressant; The ethanol extraction of Radix Curcumae can make the active rising of the GPT of carbon tetrachloride culture medium, the inhibition carbon tetrachloride hepatocellular damage composition curcumin of Radix Curcumae etc.; The ethanol extraction of Radix Curcumae also has significant inhibitory effect to the galactosamine hepatocellular damage; Radix Curcumae has the antifungal effect, and the volatile oil antifungal activity of Radix Curcumae shows that volatile oil is active maximum to the inhibition of Penicllium chrysogenum; The reticuloendothelial system that the Radix Curcumae polysaccharide has clearly activates activity, and phagocytic index K reaches 0.2526, explains that Radix Curcumae has strong immunocompetence; Radix Curcumae has the obvious suppression effect to the cholesterol and the content of triglyceride rising of rat blood serum, aorta and liver; Radix Curcumae alcohol extract, Radix Curcumae volatile oil, curcumin all have the effect of falling plasma cholesterol, beta lipoprotein and triglyceride; And T-CHOL, content of triglyceride in the aorta are reduced, wherein obvious with the effect of Radix Curcumae alcohol extract and curcumin especially; Chemical constituent curcumin in the Radix Curcumae and sodium deoxycholate have increase effect clearly to the rat bile output, and the effect of sodium deoxycholate is the most obvious.

Radix Et Rhizoma Rhei another name general, living army, Radix Et Rhizoma Rhei are the dry root and rhizome of polygonum rheum palmatum, Rheum tanguticum or Rheum officinale.Radix Et Rhizoma Rhei is cold in nature, and bitter in the mouth is returned spleen, stomach, large intestine, liver, pericardium channel.Have purging heat and dredging bowels, removing pathogenic heat from blood and toxic substance from the body, the function of eliminating blood stasis and inducing menstruation is used to treat the excess-heat constipation, stagnant stomachache, dysentery is not well, jaundice due to damp-heat, heat in blood is told nosebleed, conjunctival congestion, pharyngeal swelling, abdominalgia with intestinal abscess, carbuncle furuncle, blood stasis amenorrhea, traumatic injury.

Main pharmacodynamics composition in the Radix Et Rhizoma Rhei has anthracene derivative, glycosides compound, tannin class, organic acid, volatile oil etc.Anthracene derivative: 1. dissociated anthraquinone derivant, like aloe-emodin, chrysaron, chrysophanol, emodin, isoemodin, physcione, chrysophanic acid; 2. combined anthraquinone chemical compound: the list of chrysophanic acid, aloe-emodin, chrysophanol and two glycoside; The monosaccharide glycoside of emodin, physcione; 3. anthrol and anthrone chemical compound: reidin, palm leaf dianthrone and with the bonded glycoside of sugar such as Sennoside A, B, C, D, E, F etc.Glycosides compound: rhaponticin, 3,5,4 '-resveratrol alkene 1 '-O-β-D-(6 '-O-Galla Turcica (Galla Helepensis) acyl) glycoside, 3,5,4 '-trihydroxy stilbene alkene-4 '-O-β-D-glucopyanoside etc.Tannin class: galloyl glucose, d-catechin, gallic acid, tetrarin etc.Tetrarin gets gallic acid, cinnamic acid and rheosmin through hydrolysis.Contain volatile oil, plant sterol, resin and organic acid etc. in addition.

The pharmacological research of Radix Et Rhizoma Rhei shows that Radix Et Rhizoma Rhei has discharge function, and the Senna fruit glycoside in the Radix Et Rhizoma Rhei decomposes generation chrysophanic acid anthrone under the effect of intestinal bacteria enzyme, and the chrysophanic acid anthrone stimulates big intestinal mucosa, makes the enterokinesia increase and rushes down following.Also can suppress Na+ on the enterocyte film, K+-ATP enzyme in addition, hinder the Na+ transhipment, the enteral osmotic pressure is raise, keep large quantity of moisture, promote enterokinesia and rush down down; Anastalsis, its effective ingredient α-catechin, gallic acid can promote hematoblastic adhesion and aggregation capability, platelet increasing number and fibrinogen content, it is active to reduce Antithrombin III, makes injured partial vasoconstriction, and then hemostasis.Anti-infectious function, the antibiotic effective ingredient in the Radix Et Rhizoma Rhei are chrysophanic acid, emodin, aloe-emodin, and Radix Et Rhizoma Rhei can suppress bacterial nucleic acid and protein synthesis; Suppress the bacterium living beings oxidase system; Inducement interferon.

Herba Hedyotidis Diffusae is the herb of Rubiaceae cerastium plant Herba Hedyotidis Diffusae Hedyotis diffusaWilld. [Oldenlandia diffusa (Willd.) Roxb.].Herba Hedyotidis Diffusae is cool in nature, and sweet in the mouth, light is returned stomach, large intestine, small intestine meridian.Have heat-clearing and toxic substances removing, inducing diuresis to remove edema, the effect of promoting blood circulation and stopping pain is mainly used in treatment acute appendicitis (appendicitis), furuncle toxic swelling, jaundice due to damp-heat, diseases such as dysuria.

Herba Hedyotidis Diffusae contains the acid of rubichloric acid., rubichloric acid., goes the acid of acetate rubichloric acid., all square rafter glycoside acid, Herba Paederiae time glycoside, Herba Paederiae time glycoside methyl ester, ursolic acid, cupreol, hentriacontane, stigmasterol, oleanolic acid, daucosterol, right-coumaric acid etc.

The pharmacological research of Herba Hedyotidis Diffusae shows to have antitumor action, and the tumor cell of acute lymphoblastic type, granulocyte type, monocyte type and chronic granulocyte type is had strong inhibitory action; Antibacterial action, the decoct of Herba Hedyotidis Diffusae is to staphylococcus aureus, shigella flexneri, to tool inhibitory action such as Bacillus typhi, bacillus pyocyaneus; Antiinflammation, the decoct of Herba Hedyotidis Diffusae have experimental appendicitis rabbit stimulates RE yarn system hypertrophy, increases cytophagous phagocytic activity, and makes the densification of argentophile substance tendency, the defence capability of enhancing body and reach antiphlogistic effect.Decoct is irritated stomach has the inhibition proliferative effect to initial immunity mouse spleen ABC.The water extract lumbar injection can strengthen the inductive delayed hypersensitivity of special-shaped mouse boosting cell to mice; The increased dosage amount lumbar injection can increase mice spleen antibody secreting cell number (PFC).

Borneolum Syntheticum is claimed borneolum syntheticum, borneol, Chinese mugwort powder, knot sheet again, is divided into two types of BORNEOLUM SYNTHETICUM and Blumeae preparatum Tabellae.BORNEOLUM SYNTHETICUM is that raw material is through the synthetic Borneolum Syntheticum of chemical method with Oleum Terebinthinae, Camphora etc.; Blumeae preparatum Tabellae is the crystallization of the bright leaf of Compositae Herba Blumeae Balsamiferae platymiscium Balsamiferou Blumea Herb through steam distillation, cooling gained, claims again in " Chinese mugwort powder " or " knot sheet ".The Borneolum Syntheticum cold nature, acrid in the mouth, hardship, GUIXIN, spleen, lung meridian.Have the refreshment of having one's ideas straightened out, the clearing away heat to alleviate pain effect is mainly used in the calentura coma, convulsion is fainted, the apoplexy syncope due to accumulation of phlegm, and stagnation of QI sudden syncope, the attacked by pestiferous factors stupor, conjunctival congestion, aphtha, laryngopharynx swelling and pain, auditory meatus is suppurated.

Borneolum Syntheticum is the crystallization that from the resin of Borneolum Syntheticum and volatile oil, obtains, and is to be close to pure dextro Borneolum Syntheticum.Contain multiple ter penoids in the resin of Borneolum Syntheticum and the volatile oil.Except that Borneolum Syntheticum, still contain sesquiterpenes such as Humuleno, beta-elemene, caryophyllene, triterpenoids such as oleanolic acid, alphitolic acid, asiatic acid, dipterocarpol, dryobalanone, erythrodiol.

Monas cuspurpureus Went is claimed red song, red song, red rice, good fortune song, monascus, red rice, red groove again, is mycelium and the spore of Mycophyta Ascomycetes Aspergillales Aspergillaceae Monas cuspurpureus Went Monascus purpureus Went., and warm in nature, sweet in the mouth is returned liver; Spleen; Stomach; Large intestine channel.Monas cuspurpureus Went has the stomach function regulating of helping digestion, promoting blood circulation and stopping pain, and spleen invigorating, the function of dry stomach is mainly used in the treatment retention of food and drink, and chest and diaphragm is full vexed, dyspepsia.

Modern pharmacological research shows behind the red koji fermentation separable to coenzyme Q10, and coenzyme Q10 is the activator of cellular metabolism and Cellular respiration, can improve the mitochondrial respiratory function, the accelerating oxidation phosphorylation reaction.Itself is again the natural oxidant that cell self produces, and can suppress mitochondrial peroxidating, and the function of protection biofilm structure integrity is arranged.Immunity there is non-specific potentiation, can improves cytophagous phagocytic rate, increase production of antibodies, improve the T cell function.

The present invention provides a kind of method for preparing of Chinese medicine composition of above-mentioned treatment hepatitis on the other hand, comprises making above-mentioned all medical materials (being Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae, Radix Curcumae, Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus, Fel Serpentis and Monas cuspurpureus Went) fermentation.

Wherein, described method for preparing comprises as follows step in sequence:

1) preparation sterilization medicated powder

Medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae are carried out dried respectively, then exsiccant medical material is pulverized, carry out sterilization treatment behind the medicinal powder mix homogeneously after will pulverizing then, make sterilization medicated powder;

2) sterilization medicated powder fermentation

Add Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus and Fel Serpentis to sterilization in the medicated powder, being mixed into the fermentation material after, add Monas cuspurpureus Went and carry out said fermentation, obtain fermenting mixture, be dried then, pulverize, make medicine activity component of the present invention.

Particularly, the temperature of the dried described in the step 1) is 70-80 ℃, and the time is 7-8 hour; The granularity of the medicinal powder after the said pulverizing is the 80-200 order; The temperature of said sterilization treatment is 80-100 ℃, and the time is 0.5-2 hour.

Especially, the granularity of medicinal powder is the 80-150 order; Described sterilization treatment adopts flowing steam to carry out described sterilization, and described sterilising temp is 100 ℃, and sterilization time is 1 hour.

Wherein, Also add entry in the mixture of said sterilization medicated powder step 2) and Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus, Fel Serpentis, wherein the weight of water is 1 with the ratio of the gross weight of medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae, Radix Curcumae, Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus and Fel Serpentis: 1-3;

Carry out said fermentation after adding Monas cuspurpureus Went in the said fermentation material, fermentation temperature is 26 ± 1 ℃, and fermentation time is 5-10 days, and fermentation humidity is 50-100%.

Particularly, said water is pure water; The weight of said water is preferably 1 with the ratio of the gross weight of medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae, Radix Curcumae, Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus and Fel Serpentis: 1-2; Described fermentation humidity is preferably 75-100%, and fermentation time is 5-7 days.

Wherein, the dried moisture content of said fermenting mixture is 0-5%, and the granularity after said fermenting mixture is pulverized is the 80-200 order.

Another aspect of the invention provides a kind of pharmaceutical preparation that prevents and/or treats hepatitis of being processed by acceptable auxiliary combination on above-mentioned arbitrary said Chinese medicine composition and the pharmaceutics.

Wherein, pharmaceutical composition of the present invention can be processed clinical acceptable peroral dosage form by tradition or modern production technology with acceptable auxiliary on the pharmaceutics.As capsule, tablet, granule,, pill, oral liquid etc.Used excipient substance can be starch, dextrin, lactose, microcrystalline cellulose, gelatin, sucrose, magnesium stearate etc.Need long-term prescription clinically, process solid preparation and store conveniently, the patient takes facility, also meeting the market requirement more.Preferred dosage form is capsule, granule, tablet.

Further aspect of the present invention provides a kind of above-mentioned arbitrary said Chinese medicine compositions to treat and/or prevent the application of the medicine of hepatitis in preparation.

Pharmaceutical composition of the present invention has following advantage:

1, medicament composing prescription compatibility science of the present invention, determined curative effect, safe, quality controllable;

2, pharmaceutical composition of the present invention has heat-clearing and toxic substances removing, and the effect of blood stasis-eliminating and stagnation-dissipating is used to treat the acute and chronic hepatitis that belongs to syndrome of dampness-heat of liver and gallbladder and syndrome of static blood blocking collaterals;

3, pharmaceutical composition action pathway of the present invention is many, and drug target is many, and mechanism of action is unique, and it is rapid to eliminate clinical symptoms, has the effect of excellent transaminase lowering, and does not rebound after transaminase's reduction;

4, pharmaceutical composition of the present invention is through behind the biofermentation, and the mutual synergism of active constituents of medicine is to crucial pathology link; Promote human body immunity improving power; Regulate and enhances human body metabolism function, make by the liver organization of virus damage to obtain repairing, reach the effect of treating both the principal and secondary aspects of a disease;

5, Chinese medicine composition of the present invention can effectively reduce the red matter of blood gallbladder, and its jaundice eliminating effect is particularly outstanding, can eliminate the clinical symptoms of hepatitis fast;

6, the dosage of medicine of the present invention is low, and the method for preparing of medicine is simple, and process conditions are gentle, and with low cost, expense is low.

The specific embodiment

Below come further to set forth the beneficial effect of medicine according to the invention through Test Example, these Test Example have comprised the pharmacodynamics test of medicine of the present invention.

1 couple of carbon tetrachloride (CCL of Test Example ₄) due to the influence of acute liver injury

Test material:

Medicine capsule of the present invention; Positive control drug: bifendate: emerging magnificent pharmaceutical factory, Guangzhou produces, lot number 910107, and accurate word (88) A29-081 of medicine are defended in Guangdong.

Test method:

Choosing NIH is 70 of healthy mices, and body weight is the 22-25 gram, is divided into normal group at random; Blank model group; Four various dose groups such as bifendate matched group and medicine I of the present invention, II, III, IV, all by 20ml/kg body weight gastric infusion, normal group and blank control group are given the distilled water of equivalent.

First gastric infusion is two days before the experiment, once a day, second day afternoon lumbar injection 0.1% (CCL ₄) Oleum Arachidis hypogaeae semen 10ml/kg body weight once; Normal group gives equivalent Oleum Arachidis hypogaeae semen, continues administration on the 3rd day, and the upper and lower noon respectively once; Fasting is got blood with capillary glass tube from the eye socket rear vein beard after 12 hours and is surveyed serum paddy transaminase (SGPT, reitman-frankel method); And get liver and cut into slices by routine paraffin wax, do the pathology histological examination, check result is with the degree of "+" expression pathological change."-" expression liver is normal; "+" expression hepatocyte only has a small amount of degeneration and spotty necrosis or a small amount of cell infiltration; " +++" shown the neutrophilic infiltration that hepatocyte most of degeneration necrosis occurs and fills the air; " ++ " shown and is positioned between the two, and result's analysis is with integration method, and "-" is 0 minute, and "+" is 1 minute, and " ++ " is that 2 minutes " +++" is 3 minutes.

Table 1 couple CCL ₄Due to the influence (X ± SD) of hepatic injury mice SGPT

Group	Dosage (mg/kg)	Number of animals (only)	SGPT(υ/100ml)
				Normally	-	9	40±23
Blank	-	12	160±47
				Bifendate	10	10	45±22 **
Medicament capsule of the present invention (I group)	250	10	82±61 **
				Medicament capsule of the present invention (II group)	500	9	98±59 *
Medicament capsule of the present invention (III group)	1000	9	64±32 **
				Medicament capsule of the present invention (IV group)	1500	10	73±30 **

Annotate: compare with blank model group, ^*Show＜0.05, ^*P＜0.01 (down together)

The experimental result of table 1 shows: four various dose of Chinese medicinal composition capsules of the present invention, all can reduce CCL ₄Due to the serum glutamic pyruvic transminase SGPT of hepatic injury mice, with blank control group relatively, the difference significance, with the bifendate group relatively, difference does not have significance.

Table 2 couple CCL ₄Due to the influence (X ± SD) of hepatic injury mouse liver pathological change

Table 3 couple CCL ₄Due to the influence (X ± SD) of hepatic injury mouse liver pathological change

Table 2,3 visible, CCL ₄Due to the blank model group hepatocellular degeneration of hepatic injury obvious, especially cell infiltration is extensive, hepatic necrosis is serious; Bifendate group hepatic pathology improves not obvious, and each item index and blank control group compare, and difference does not have significance.Medication I group, hepatic pathology does not have obvious improvement, compares P＞0.05 with blank control group; And medication II group, pathological change begins to alleviate, especially medication III group, IV group, and hepatocellular degeneration alleviates, and inflammation is downright bad obviously to be reduced, and organizational structure is near normal.Compare with blank control group and bifendate group, difference all has highly significant property, measures the result with SGPT and conforms to.

Result of the test shows: pharmaceutical composition of the present invention is to CCL ₄Cause the white mice hepatic injury and have protection and therapeutical effect, it not only can reduce CCL ₄Due to the downright bad SGPT that is caused of hepatocellular degeneration increase, main is to resist CCL ₄Due to hepatic injury, can promote disappearing of hepatocyte inflammation, impel the recovery of liver function.The down visible pathological change of mirror obviously alleviates, and the hepatocyte organizational structure is near normal, and the improvement degree is superior to bifendate, and difference has the highly significant meaning.

The influence of 2 pairs of isothiocyanic acid α-Nai Zhis of Test Example (ANIT) hepatic injury

Test material:

Medicine capsule of the present invention; Positive control drug: danshitong capsules: Shantou, Guangdong pharmaceutical factory produces, lot number 910102, and Guangdong is defended accurate word (85) C1-195 of medicine numbers.

Test method:

Choosing NIH is healthy mice, and body weight is the 23-25 gram, and male and female half and half are divided into normal group, blank model group, the logical group of cholelithiasis and administration low dose group and high dose group at random, and each group is all by 10ml/kg body weight gastric infusion.Normal group and blank control group give the equivalent distilled water, and positive control drug is selected danshitong capsules for use.

First gastric infusion is three days before the experiment, and morning every day, once that afternoon was with 50mg/kg body weight ANIT Oleum Arachidis hypogaeae semen suspension oral gavage (0.2ml/10g body weight) after the last administration.Continued administration then two days, every day secondary.Fasting is 12 hours after the last administration.Get blood with capillary glass tube from the eye socket rear vein beard, survey SGPT and STB, the result sees table 4.

The influence of hepatic injury mice SGPT and serum total bilirubin due to the table 4 couple ANIT (X ± SD)

The testing result of table 4 shows, pharmaceutical composition of the present invention increases liver injury mice serum glutamate pyruvate transaminase due to the ANIT and STB has significant inhibitory effect, with blank control group relatively, the equal significance of difference.Though the danshitong capsules matched group is also seen SGPT and STB and is reduced, compares the difference nonsignificance with blank control group.

Pharmaceutical composition of the present invention can obviously alleviate hepatic injury due to the hepatotoxic agent ANIT, reduces SGPT and serum bilirubin, with blank control group relatively, difference has the highly significant meaning.

The influence of 3 pairs of rat ethanol of Test Example liver injury

Test material:

Medicine capsule of the present invention; Positive control drug: danshitong capsules Schizandrol: brilliance pharmaceutical factory in Guangzhou produces, lot number 910101, and Guangdong is defended accurate word (82) A7-064 of medicine numbers.

Test method:

Choosing SD is healthy white rat, body weight 190-210 gram, and male and female half and half are divided into normal group, blank model group, Schizandrol group and low dosage medication group and middle dosage medication group at random.Each group is all by 1ml/100g body weight administration (administration by gavage), and normal group and blank control group give the equivalent distilled water, administration in morning every day; Give 60% ethanol 1ml/100g body weight afternoon and irritate stomach, continuous 15 days, after the last administration; Fasting 12 hours is got blood and is surveyed SGPT, T-CHOL, triglyceride, and execution is immediately got liver and cut into slices by routine paraffin wax; Do histopathologic examination, the result representes with "+"."+" shows only has a small amount of degeneration or a small amount of spotty necrosis in the lobules of liver; " +++" shown and occurred most of degeneration in the lobules of liver or show occurring filling the air big lamellar of spotty necrosis or many places and the necrosis of bridge joint appearance in the lobules of liver; " ++ " shown and occupy between the two, and result's analysis is with integration method, and "-" is 0 minute, and "+" is 1 minute, and " ++ " is that 2 minutes " +++" is 3 minutes.

The cruel influence of table 5 couple ethanol liver damage rat SGPT, serum total cholesterol and glycerol three (X ± SD)

Table 5 is the result show, capsule 1000mg/kg of the present invention has reduction effect (P＜0.05) to the SGPT of ethanol liver damage rat and serum triglycerides and cholesterol, and 250mg/kg then acts on not obvious.Schizandrol has the reduction effect to SGPT, and not obvious to serum total cholesterol and triglyceride effect.

The influence of table 6 pair ethanol liver damage rat liver pathological change (X ± SD)

The influence of table 7 pair ethanol liver damage rat liver pathological change (X ± SD)

Table 6,7 testing result show that ethanol can cause the tangible pathological change of rat liver, shows as hepatocellular degeneration and necrosis, and cell infiltration in the liver, and extent of disease is extensive, and some is the large stretch of necrosis in many places, degeneration, cell infiltration.Dose groups in the pharmaceutical composition of the present invention (1000mg/kg) has hepatic injury effect due to the anti-ethanol, shows as that pathological change is light, necrotic extent is little.JIANGANLING JIAONANG also is that certain anti-detrimental effect is arranged, but anti-hepatocellular degeneration aspect compares with medicine of the present invention, and effect is relatively poor.

Ethylism can directly cause hepatocellular damage, and SGPT is raise, and can cause hepatocyte intracellular metabolite obstacle again, causes hyperlipemia and fatty liver.Chinese medicine composition of the present invention has anti-ethanol to cause hepatic injury, and the effect of SGPT and lipid in the reduction blood is compared with blank control group, and difference has significance.Pathologic finding under the mirror, pharmaceutical composition group of the present invention have many cases hepatocyte pathology to change basic the recovery normally, compare with blank control group, have the significance difference opposite sex.

In order to study the toxic action that Chinese medicine composition of the present invention possibly exist body, acute toxicity test and long term toxicity test have been carried out.

Test Example 4 acute toxicity tests

Choosing NIH is 20 of healthy mices, and body weight is the 18-20 gram, male and female half and half.First fasting is 12 hours before the experiment, and during experiment, the dose with the tolerant Cmax of white mice, maximum volume is made into 30% concentration with medicine of the present invention, according to 0.3ml/mg body weight gastric infusion 1 time, observes 7 days.Experimental result show Chinese medicine composition of the present invention to the LD50 value of mice greater than the 9g/kg body weight; The total dosage of its whole day is the 27g/kg body weight, is equivalent to 360 times of clinical dosage, and medicine of the present invention gives the maximum tolerated dose of mice lavage administration greater than the 27g/kg body weight, and medicine of the present invention does not have acute toxic reaction.

Test Example 5 long term toxicity tests

After animal feeding observed for 1 week; Selecting each item index normal N IH is 96 of healthy mices, is divided into high dose group (6g/kg body weight), middle dose groups (3g/kg body weight), low dose group (1.5g/kg body weight) and matched group at random, 24 of every treated animals; Male and female half and half, body weight are 110-130g.During off-test, randomly draw 20 for every group and measure each item index, residue is put to death and is cutd open inspection.

High, medium and low dose groups dosage is equivalent to 80,40,20 times of clinical consumption, is equivalent to 6,3,1.5 times of pharmacodynamics effective dose respectively.Medicine is prepared with 5% Radix Acaciae senegalis distilled water suspension, presses 10ml/kg body weight per os gastric infusion, and every day 2 times, matched group gives 5% Radix Acaciae senegalis distilled water suspension of equivalent.Detect index, and be aided with the pathological examination that animal is respectively organized internal organs, the toxicity situation of overall merit medicine with general performance, body weight, hematology and serum biochemistry index before and after the animals administer, routine urinalysis, organ weights equipotential.

The result shows: medicament capsule of the present invention changes the no significance difference opposite sex to the weight of animals, and animal growth is normal; Each item inspection index of high, medium and low dose groups animal is not seen obviously unusual; The result of histopathologic examination shows that three dose groups animals are respectively organized the internal organs no abnormality seen.Show that medicine of the present invention is not good at the phase toxic reaction, be safe medication.

The artificial Moschus who uses in the embodiment of the invention joins fragrant pharmaceutcal corporation, Ltd by Beijing to be provided; The artificial Calculus Bovis is provided by Henan Province's work of nature pharmaceutcal corporation, Ltd; Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Fel Serpentis, Radix Curcumae, Monas cuspurpureus Went are available from the strong peace hall in Guangzhou pharmaceutcal corporation, Ltd;

The capsule preparation of embodiment 1 medicine of the present invention

1, according to following weight proportion prepare raw material (* 10g):

Radix Notoginseng 80, Rhizoma Coptidis 100, Radix Scutellariae 30, Cortex Phellodendri 90, Radix Et Rhizoma Rhei 50, Agkistrodon SHECAO 50, Fel Serpentis 20, Borneolum Syntheticum 1, artificial Calculus Bovis 30, artificial Moschus 1, Radix Curcumae 45, Monas cuspurpureus Went 50

2, preparation mixed powder

1) drying of medical material

To pass through and clean Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, Radix Et Rhizoma Rhei, the Agkistrodon SHECAO medical material remove silt and be respectively charged into the exsiccator inner drying, and obtain dry medical material, wherein, baking temperature is 70 ℃, dry 8 hours;

2) pulverizing of dry medical material

Dry medical material is pulverized respectively, and the medicinal powder granularity after the pulverizing is the 100-200 order, obtains Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, Radix Et Rhizoma Rhei, Agkistrodon SHECAO medicinal powder respectively;

3) medicinal powder mixes, sterilizes

Behind Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, Radix Et Rhizoma Rhei, Agkistrodon SHECAO medicinal powder mix homogeneously; Place horizontal rectangle pressure steam sterilizer (Hunan gold one sail pharmaceutical equipment Industrial Co., Ltd., model: carry out flowing steam sterilization YXQ.WF22S-1.2); Make sterilization medicated powder after the cooling; Wherein, the temperature of flowing steam sterilization is 100 ℃, and sterilization time is 1 hour;

3, medicated powder fermentation

1) with artificial Calculus Bovis, artificial Moschus and Fel Serpentis join the sterilization medicated powder in and stir; Make mixed powder; Then add pure water to mixed powder; Make fermentation medicated powder, the weight of the pure water of adding is 1: 1 with the ratio of the gross weight of medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, artificial Calculus Bovis, artificial Moschus and Fel Serpentis;

2) the leaven Monas cuspurpureus Went is added in the fermentation medicated powder, stirs, ferment, make fermenting mixture, wherein, fermentation temperature is 26 ± 1 ℃, and fermentation time is 7 days, and fermentation humidity is 75%;

3) fermenting mixture is placed carry out drying in the exsiccator, pulverize then and promptly get, wherein, the moisture content that is dried to fermenting mixture is 5%, and the granularity of the fermenting mixture after the pulverizing is the 150-200 order;

4, preparation capsule

With after the adjuvant Pulvis Talci mixes, the snap fit capsule of packing into promptly gets with the fermenting mixture after pulverizing.

The preparation tablets of embodiment 2 medicines of the present invention

1, according to following weight proportion prepare raw material (* 10g):

Radix Notoginseng 180, Rhizoma Coptidis 30, Radix Scutellariae 100, Cortex Phellodendri 20, Radix Et Rhizoma Rhei 80, Agkistrodon SHECAO 100, Fel Serpentis 5, Borneolum Syntheticum 40, artificial Calculus Bovis 20, artificial Moschus 20, Radix Curcumae 30, Monas cuspurpureus Went 60

2, preparation mixed powder

1) drying of medical material

Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medical material are respectively charged into the exsiccator inner drying, obtain dry medical material, wherein, baking temperature is 80 ℃, dry 7 hours;

2) pulverizing of dry medical material

Dry medical material is pulverized respectively, and the medicinal powder granularity after the pulverizing is the 80-100 order, obtains Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medicinal powder respectively;

3) medicinal powder mixes, sterilizes

Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medicinal powder mix homogeneously be placed in the horizontal rectangle pressure steam sterilizer (Hunan gold one sail pharmaceutical equipment Industrial Co., Ltd.) carry out flowing steam sterilization; Make sterilization medicated powder after the cooling; Wherein, The temperature of flowing steam sterilization is 100 ℃, and sterilization time is 2 hours;

3, medicated powder fermentation

1) with artificial Calculus Bovis, artificial Moschus and Fel Serpentis join the sterilization medicated powder in and stir; Make mixed powder; Then add pure water to mixed powder; Make fermentation medicated powder, the weight of the pure water of adding is 1: 2 with the ratio of the gross weight of medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, artificial Calculus Bovis, artificial Moschus and Fel Serpentis;

2) the leaven Monas cuspurpureus Went is added in the fermentation medicated powder, stirs, ferment, make fermenting mixture, wherein, fermentation temperature is 26 ± 1 ℃, and fermentation time is 5 days, and fermentation humidity is 100%;

3) fermenting mixture is placed carry out drying in the exsiccator, pulverize then and promptly get, wherein, the moisture content that is dried to fermenting mixture is 2.5%, and the granularity of the fermenting mixture after the pulverizing is the 150-200 order;

4, preparation tablet

Fermenting mixture after pulverizing with after supplementary product starch mixes, is pressed into tablet.

The granule preparation of embodiment 3 medicines of the present invention

1, according to following weight proportion prepare raw material (* 10g):

Radix Notoginseng 100, Rhizoma Coptidis 85, Radix Scutellariae 40, Cortex Phellodendri 20, Radix Et Rhizoma Rhei 20, Agkistrodon SHECAO 80, Fel Serpentis 20, Borneolum Syntheticum 2, artificial Calculus Bovis 3, artificial Moschus 2, Radix Curcumae 1, Monas cuspurpureus Went 20

2, preparation mixed powder

1) drying of medical material

Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medical material are respectively charged into the exsiccator inner drying, obtain dry medical material, wherein, baking temperature is 80 ℃, dry 7 hours;

2) pulverizing of dry medical material

Dry medical material is pulverized respectively, and the medicinal powder granularity after the pulverizing is the 100-150 order, obtains Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medicinal powder respectively;

3) medicinal powder mixes, sterilizes

Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medicinal powder mix homogeneously be placed in the horizontal rectangle pressure steam sterilizer (Hunan gold one sail pharmaceutical equipment Industrial Co., Ltd.) carry out flowing steam sterilization; Make sterilization medicated powder after the cooling; Wherein, The temperature of flowing steam sterilization is 100 ℃, and sterilization time is 0.5 hour;

3, medicated powder fermentation

1) with artificial Calculus Bovis, artificial Moschus and Fel Serpentis join the sterilization medicated powder in and stir; Make mixed powder; Then add pure water to mixed powder; Make fermentation medicated powder, the weight of the pure water of adding is 1: 3 with the ratio of the gross weight of medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, artificial Calculus Bovis, artificial Moschus and Fel Serpentis;

2) the leaven Monas cuspurpureus Went is added in the fermentation medicated powder, stirs, ferment, make fermenting mixture, wherein, fermentation temperature is 26 ± 1 ℃, and fermentation time is 10 days, and fermentation humidity is 50%;

3) fermenting mixture is placed carry out drying in the exsiccator, pulverize then and promptly get, wherein, the moisture content that is dried to fermenting mixture is 0.5%, and the granularity of the fermenting mixture after the pulverizing is the 150-200 order;

4, preparation granule

Fermenting mixture after pulverizing with after the adjuvant dextrin mixes, is pressed into granule.

The pill preparation of embodiment 4 medicines of the present invention

1, according to following weight proportion prepare raw material (* 10g):

Radix Notoginseng 160, Rhizoma Coptidis 30, Radix Scutellariae 120, Cortex Phellodendri 100, Radix Et Rhizoma Rhei 100, Agkistrodon SHECAO 20, Fel Serpentis 3, Borneolum Syntheticum 50, artificial Calculus Bovis 1, artificial Moschus 20, Radix Curcumae 2, Monas cuspurpureus Went 30

2, preparation mixed powder

1) drying of medical material

Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medical material are respectively charged into the exsiccator inner drying, obtain dry medical material, wherein, baking temperature is 75 ℃, dry 8 hours;

2) pulverizing of dry medical material

Dry medical material is pulverized respectively, and the medicinal powder granularity after the pulverizing is the 150-200 order, obtains Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medicinal powder respectively;

3) medicinal powder mixes, sterilizes

Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae medicinal powder mix homogeneously be placed in the horizontal rectangle pressure steam sterilizer (Hunan gold one sail pharmaceutical equipment Industrial Co., Ltd.) carry out flowing steam sterilization; Make sterilization medicated powder after the cooling; Wherein, The temperature of flowing steam sterilization is 100 ℃, and sterilization time is 1 hour;

3, medicated powder fermentation

1) with artificial Calculus Bovis, artificial Moschus and Fel Serpentis join the sterilization medicated powder in and stir; Make mixed powder; Then add pure water to mixed powder; Make fermentation medicated powder, the weight of the pure water of adding is 1: 1 with the ratio of the gross weight of medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, artificial Calculus Bovis, artificial Moschus and Fel Serpentis;

2) the leaven Monas cuspurpureus Went is added in the fermentation medicated powder, stirs, ferment, make fermenting mixture, wherein, fermentation temperature is 26 ± 1 ℃, and fermentation time is 7 days, and fermentation humidity is 75%;

3) fermenting mixture is placed carry out drying in the exsiccator, pulverize then and promptly get, wherein, the moisture content that is dried to fermenting mixture is 2.5%, and the granularity of the fermenting mixture after the pulverizing is the 150-200 order;

4, preparation pill

Fermenting mixture and adjuvant Mel after pulverizing are joined in the pellet processing machine, process pill.

Claims (9)

1. treat the hepatitis Chinese medicine composition for one kind; It is characterized in that crude drug is: Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae, Fel Serpentis, Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus, Radix Curcumae, Monas cuspurpureus Went, the weight portion proportioning of said crude drug is: Radix Notoginseng 80-180, Rhizoma Coptidis 30-100, Radix Scutellariae 30-120, Cortex Phellodendri 20-100, Radix Et Rhizoma Rhei 20-100, Herba Hedyotidis Diffusae 20-100, Fel Serpentis 5-20, Borneolum Syntheticum 1-50, artificial Calculus Bovis 1-30, artificial Moschus 1-20, Radix Curcumae 1-45, Monas cuspurpureus Went 20-60.

2. treat the hepatitis Chinese medicine composition for one kind; It is characterized in that crude drug is: Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae, Fel Serpentis, Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus, Radix Curcumae, Monas cuspurpureus Went, the weight portion proportioning of said crude drug is: Radix Notoginseng 100-160, Rhizoma Coptidis 30-85, Radix Scutellariae 40-100, Cortex Phellodendri 20-90, Radix Et Rhizoma Rhei 20-80, Herba Hedyotidis Diffusae 20-80, Fel Serpentis 3-20, Borneolum Syntheticum 2-40, artificial Calculus Bovis 3-20, artificial Moschus 2-20, Radix Curcumae 2-30, Monas cuspurpureus Went 30-50.

3. method for preparing of treating the hepatitis Chinese medicine composition according to claim 1 or claim 2 is characterized in that comprising making said fermenting raw materials.

4. method for preparing as claimed in claim 3 is characterized in that comprising as follows step in sequence:

1) preparation sterilization medicated powder

Medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Curcumae, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae are carried out dried respectively, then exsiccant medical material is pulverized, carry out sterilization treatment behind the medicinal powder mix homogeneously after will pulverizing then, make sterilization medicated powder;

2) sterilization medicated powder fermentation

Add Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus and Fel Serpentis to sterilization in the medicated powder, being mixed into the fermentation material after, add Monas cuspurpureus Went and carry out said fermentation, obtain fermenting mixture, be dried then, pulverize, make medicine activity component of the present invention.

5. method for preparing as claimed in claim 4, the baking temperature that it is characterized in that the dried described in the described step 1) is 70-80 ℃, be 7-8 hour drying time; The granularity of the medicinal powder after the said pulverizing is the 80-200 order; The temperature of said sterilization treatment is 80-100 ℃, and sterilization time is 0.5-2 hour.

6. method for preparing as claimed in claim 5, the granularity that it is characterized in that said medicinal powder is the 80-150 order; Described sterilization treatment adopts flowing steam to carry out described sterilization, and described sterilising temp is 100 ℃, and sterilization time is 1 hour.

7. method for preparing as claimed in claim 4; It is characterized in that step 2) in the mixture of said sterilization medicated powder and Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus, Fel Serpentis in add entry, wherein the weight of water is 1 with the ratio of the gross weight of medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae, Radix Curcumae, Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus and Fel Serpentis: 1-3;

Carry out said fermentation after adding Monas cuspurpureus Went in the said fermentation material, fermentation temperature is 26 ± 1 ℃, and fermentation time is 5-10 days, and fermentation humidity is 50-100%.

8. method for preparing as claimed in claim 7, the weight that it is characterized in that said water is 1 with the ratio of the gross weight of medical material Radix Notoginseng, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Radix Et Rhizoma Rhei, Herba Hedyotidis Diffusae, Radix Curcumae, Borneolum Syntheticum, artificial Calculus Bovis, artificial Moschus and Fel Serpentis: 1-2; Said fermentation time is 5-7 days, and humidity is 75-100%.

9. method for preparing as claimed in claim 4 is characterized in that the moisture content that said fermenting mixture is dried to is 0-5%, and the granularity after said fermenting mixture is pulverized is the 80-200 order.