CN103272146A - Medicine composition used for preventing and treating alcoholic fatty liver and preparation method thereof - Google Patents
Medicine composition used for preventing and treating alcoholic fatty liver and preparation method thereof Download PDFInfo
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Abstract
The invention relates to an application of a medicine composition in preparing medicine used for preventing and treating alcoholic fatty liver, wherein the medicine composition is prepared from the following raw ingredients by weight: 5 to 60 parts of penthorum chinense pursh, 5 to 15 parts of ganoderma, 5 to 10 parts of elsholtzia, 5 to 10 parts of raw barley, 5 to 10 parts of almond and pharmaceutical excipients. Meanwhile the invention provides a preparation method for the medicine composition used for preventing and treating alcoholic fatty liver; and the medicine composition is used for treating alcoholic fatty liver. The application and the preparation method have the effects that the medicine composition overcomes the disadvantage of conventional dosage form such as decoction, adopts an ultramicro pulverizing method, retains the effective constituent with clinical effects in the composition, also ensures the dissolution rate of the clinical effective constituent, ensures the clinical effects, and is obviously superior to similar medicines on the preventing and treating functions of alcoholic fatty liver.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition, particularly a kind of pharmaceutical composition and preparation method of preventing and treating alcoholic fatty liver.
Background technology
Alcoholic liver disease is the worldwide public health problem of serious threat human health.The statistical data that World Health Organization (WHO) delivered in 2007 shows that 30 years in the past, global alcoholic liver patient number increased severely to 1.3 hundred million from 1,000 ten thousand.The expert of World Health Organization (WHO) estimates that global alcoholic liver patient will reach 2.5 hundred million by 2025.The economy of bringing along with China's reform increases rapidly, China's also phenomenal growth of alcohol to oil ratio per capita, and the people up to 6.1% among the alcohol user suffers from alcoholic liver disease, and alcoholic liver disease has become the second largest hepatopathy after viral hepatitis.One of China shows that at the fatty liver disease sampling survey alcoholic fatty liver prevalence has reached 23.34%, becomes the first cause of disease of Chinese fatty liver.The control deficiency of alcoholic fatty liver also becomes the key subjects that clinical medicine, preventive medicine, social medicine and administrative department in charge of health face jointly.
Alcoholic liver disease (ALD) comprises alcoholic fatty liver, alcoholic hepatitis, alcoholic fibrosis and alcoholic cirrhosis.Its pathogenesis is comparatively complicated, still imperfectly understands at present.Alcoholic fatty liver is many simultaneously with alcoholic liver injury, and alcoholic liver injury can bring out fat hepatitis and hepatic fibrosis.Alcoholic hepatitis is a kind of pathological changes more serious than fatty liver, and about 50% alcoholic hepatitis will develop into liver cirrhosis.Liver cirrhosis can directly take place without alcoholic hepatitis, has 10% to develop into hepatocarcinoma.20%～30% develops into liver cirrhosis in the chronic alcoholic, and hepatocarcinoma person about 2%～3% is taken place.
At present making a definite diagnosis of alcoholic liver disease (ALD) is golden index with liver puncture still, and liver puncture belongs to the wound diagnosis is arranged, and is difficult for being accepted by the patient, has limited its clinical practice, finds the morning that also is difficult for ALD, early diagnosis, early treatment.So be badly in need of to seek the sensitive indicator of a kind of diagnosis ALD that is accepted by the patient easily.The doctor except alleviating alcohol addiction, symptomatic treatment, does not still have the therapy of specially good effect standard to ALD both at home and abroad, and especially early stage alcoholic liver injury does not have the specificity clinical manifestation, also lacks clear and definite research example both at home and abroad.According to incompletely statistics, China's fatty liver disease (FLD) patient majority is ALD now.The influence of the liver health of ALD is greater than non-alcoholic hepatopathy (NAFLD).
A large amount of studies show that motherland's traditional plant medicine can effectively delay the process of alcoholic fatty liver, prevents that alcoholic fatty liver from developing to alcoholic fibrosis, promotes alcoholic fibrosis to reverse.Therefore develop the advantage of motherland's traditional plant medicine treatment alcoholic liver disease, as early as possible to the enforcement intervention of early stage alcoholic liver injury, reduce or prevent the task of top priority that develops into of alcoholic liver injury.
This pharmaceutical composition is on early stage, the liver benefiting blood fat reducing side used effectively the basis to fatty liver; propose to inquire into the pretreatment of traditional plant medicine to early stage alcoholic liver injury protective effect; press parallel control, blind method design grouping; with the interim target that is defined as to the morbidity of xanthine oxidase (XO) research, alcoholic liver and early stage alcoholic liver injury clinical criteria; there is the Patients with Fatty Liver data of history of drinking history to stay shelves to all; adopt and generally acknowledge diagnosis and criterion of therapeutical effect, screen 115 routine alcoholic liver patients and carry out dividing processing.By generating the oxidized form pigment with xanthine oxidase-horseradish peroxidase-phenol-4-amino-antipyrine-xanthine (XO-HRP-PA-AAP-XAN) reaction new system, with xanthine (colorimetry) in batch detection by quantitative serum and the contrast of relevant zymetology index with self, from follow demonstrate,prove angle analysis XO whether can be used as the sensitive indicator of early stage alcoholic liver disease irritable injure; Whether can unite nitric oxide (NO), metal matrix enzyme (MMP-9), platelet derived growth factor (PDGF-BB) etc. as the pretreated indication index of medicine; At pathogenesis and the characteristics of incidence of early stage alcoholic liver injury, propose the ruling by law of ascending the clear and descending the turbid resolving depression first and treat alcoholic liver disease, to found this pharmaceutical composition and implement to intervene, observation analysis is to the influence of XO, NO, MMP-9, PDGF-BB and common liver enzyme index.
Result of study confirms, lipid peroxidation is that alcoholic liver injury brings out the Fibrotic important mechanisms of fat hepatitis regulating liver-QI, and xanthine oxidase (XO) can be used as the sensitive indicator of early stage alcoholic liver injury irritable injure, pay attention to xanthine oxidase and common liver enzyme index joint-detection, just can be used as the prompt foundation of early stage ALD in conjunction with the hemocyte inspection of facing the convenient routine of card, implement to intervene with this pharmaceutical composition, namely regulate the blood lipid metabolism of ALD, improve tcm symptom, suppress xanthine oxidase (XO) activity, be beneficial to hepatocellular energy metabolism; Also control alcoholic liver disease hemocyte inflammatory (GR%) index, reduce erythrocyte volume distributed median width (RDW), MPW (PDW), do not influence platelet count (PLT), especially the improvement of picture of the tongue is obvious before and after the treatment, prove that the pretreatment of this pharmaceutical composition can play class antioxidant sample effectiveness, clear and definite fatty liver diagnosis can be used, with low cost, clinical efficacy is remarkable, for early, reverse alcoholic fatty liver preferably, the control alcoholic liver disease provides reliable first-hand clinical data, has operability and high clinic actual value and social benefit.
Summary of the invention
The purpose of this invention is to provide a kind of pharmaceutical composition and preparation method of preventing and treating alcoholic fatty liver, be used for the treatment of alcoholic fatty liver, and can alleviate the sense of discomfort after drinking rapidly.Effect of the present invention is the drawback that this pharmaceutical composition has overcome conventional dosage forms such as decoction, adopt the method for micronizing, kept the effective ingredient that has clinical efficacy in the compositions, guaranteed the dissolution rate of clinical effective ingredient again, guaranteed its clinical efficacy, the preventive and therapeutic action of alcoholic fatty liver obviously has been better than similar medicine.
For achieving the above object, the technical solution used in the present invention provides a kind of pharmaceutical composition and preparation method of preventing and treating alcoholic fatty liver, and wherein: this pharmaceutical composition is made by following flavour of a drug by weight:
Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part.
Can also add the Chinese medicine Fructus Amomi in this pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Fructus Amomi 5-10 part.
Can also add the Chinese medicine Semen Myristicae in this pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Semen Myristicae 5-10 part.
Can also add Radix Puerariae, Flos puerariae lobatae in this pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Radix Puerariae 5-10 part, Flos puerariae lobatae 5-10 part.
A kind of preparation of drug combination method of preventing and treating alcoholic fatty liver also is provided simultaneously.
Effect of the present invention is the drawback that this pharmaceutical composition has overcome conventional dosage forms such as decoction, adopt the method for micronizing, both kept the effective ingredient that has clinical efficacy in the compositions, improved the dissolution rate of effective ingredient again to greatest extent, guarantee its clinical efficacy, had sturdy clinical basis and good and clinical curative effect.Said composition be primarily aimed at alcoholic fatty liver and drink after sense of discomfort, " ascending the clear and descending the turbid resolving depression " method for the treatment of is proposed, the liver benefiting blood fat reducing sideization sanction of being studied with Tianjin institution of higher education science and technology development fund project (20050320) forms, its compatibility is reasonable, prescription is rigorous, have the effect of control alcoholic fatty liver, and can obviously alleviate the sense of discomfort after drinking.Through this medicine composite for curing alcoholic fatty liver 132 routine clinical observation result are shown, its cure-remarkable-effectiveness rate reaches 80%, the improvement that the patients serum learns indexs such as index and platelet-derived growth factor (PDGF) vigor all obviously is better than contrasting the medicine Essentiale N/Essentiale Forte N, determined curative effect, and safe without toxic side effect.
This pharmaceutical composition obviously is better than similar medicine to the preventive and therapeutic action of alcoholic fatty liver.
The specific embodiment
In conjunction with the embodiments a kind of pharmaceutical composition and preparation method of preventing and treating alcoholic fatty liver of the present invention described in detail.
The pharmacodynamics experimentation has disclosed the mechanism of the prevention of this pharmaceutical composition and treatment alcoholic fatty liver before clinical: 1. this pharmaceutical composition can be by reducing the release of unesterified fatty acid, reduce the accumulation of TG in the liver, increase lipid metabolism, thus the control alcoholic fatty liver; 2. this pharmaceutical composition can pass through class antioxidant sample effectiveness, alleviates lipid peroxidation, alleviates hepatic fibrosis, thus the control alcoholic fatty liver; 3. this pharmaceutical composition can suppress the HSC activation and transform by reducing platelet growth derivative factor (PDGF) vigor, prevents that alcoholic fatty liver from developing to alcoholic fibrosis, thus the control alcoholic fatty liver; 4. this pharmaceutical composition can be by reducing ALT, AST activity, and the hepatic injury that ethanol is caused plays a protective role, thus the control alcoholic fatty liver; 5. this pharmaceutical composition can be beneficial to hepatocellular energy metabolism by suppressing xanthine oxidase (XO) activity, thus the control alcoholic fatty liver.
Clinical efficacy is the result show, take this pharmaceutical composition after, traditional Chinese medical science disease is uncomfortable in chest, hypochondriac pain, dizziness, breathe hard, facial dark violet, fatigue and weak, the dark white, slippery and moist fur of tongue be greasy, deep and hesitant pulse or stringy and thready pulse etc. meets the equal tool produce effects of all index of alcoholic fatty liver clinical manifestation; Self more all have clear improvement in body of the tongue, tongue fur, all index group of pulse condition; Compare with matched group all index treatment of tcm syndrome back, and treatment group total effective rate and cure-remarkable-effectiveness rate all obviously are better than matched group; Treat back tcm syndrome total effective rate and cure-remarkable-effectiveness rate treatment group apparently higher than matched group.Illustrate that its clinical therapeutic efficacy of this pharmaceutical composition obviously is better than existing similar medicine.
Pharmaceutical composition of the present invention is made by following flavour of a drug by weight:
Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part.
Can also add the Chinese medicine Fructus Amomi in this pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Fructus Amomi 5-10 part.
Can also add the Chinese medicine Semen Myristicae in this pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Semen Myristicae 5-10 part.
Can also add Radix Puerariae, Flos puerariae lobatae in this pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Radix Puerariae 5-10 part, Flos puerariae lobatae 5-10 part.
The preparation of drug combination method of control alcoholic fatty liver of the present invention, its method is as follows:
A) distillation: Herba Moslae, Semen Armeniacae Amarum or Herba Moslae, Semen Armeniacae Amarum, Semen Myristicae two in above-mentioned any one are distinguished the flavor of or three herbal medicine vapor distillations, collect volatile oil, distillate, medicinal residues, standby;
B) water extraction: all the other medicines except Herba Moslae, Semen Armeniacae Amarum or Herba Moslae, Semen Armeniacae Amarum, Semen Myristicae among the medicinal residues in a) and above-mentioned any are put in the water extraction jar, the 6-10 times of water gaging that adds described pharmaceutical composition by weight, the best is 8 times of water gagings, decoct 2 times, each 1-4 hour, the best was 2 hours, boiling back steam pressure 0.03-0.04Mpa, collecting decoction filters;
C) concentrating: with distillate and the b in a) step) water extraction filtrate in the step puts in the concentration tank, and being concentrated into relative density is 1.01-1.03, and the best is 1.02, the clear paste that temperature is 50 ℃, thickening temperature 50-100 ℃;
D) precipitate with ethanol: concentrated solution is put in the Alcohol-settling tank, slowly adds 95% ethanol and makes it contain alcohol amount to reach 50%-75%, and the best is 65%, after fully stirring, leaves standstill 8-20 hour, and the best is 12 hours, filters;
E) reclaim ethanol: filtrate is put in the reclaim under reduced pressure jar, decompression recycling ethanol, and being concentrated into relative density is 1.04-1.07, and the best is 1.05-1.06, and the thick paste that temperature is 45 ℃, gets water extract by thickening temperature 40-100 ℃.
F) preparation of granule:
A ') with e) water extract in the step is tiled in the vacuum drying oven vacuum drying.Vacuum-0.06～-0.09Mpa, temperature 40-100 ℃, get dry extract;
B ') dried cream powder is broken into impalpable powder, crosses 200 mesh sieves;
C ') dried cream powder is blended into an amount of dextrin, sieve, and mix homogeneously, incorporation time 10-50 minute, the best was 30 minutes;
D ') mixed dried cream powder 95% alcohol granulation was granulated 7 minutes best granulation time time 3-10 minute;
E ') with d ') in made wet granular be tiled in the drying baker drying, shop layer thickness about 1-4cm, the about 2cm of the best, baking temperature 50-100 ℃;
F ') with dried granule granulate, be 14 purpose screen cloth granulate with the order number, spray into the volatile oil in a) step, mix homogeneously;
G ') pack, every packed 0.3-0.5g;
In more than forming, weight is calculated with crude drug, and part is weight portion, as if being unit with the gram, more than composition can be made into a pharmaceutical preparation 10-35 preparation unit, and described preparation unit refers to, the final drug preparation of making, as make a solid preparation 10-35 unit, oral liquid ... milliliter etc.
More than form the preparation that can be made into 1-6 taking dose, as tablet, make 18, each taking dose 3-18 sheet can be taken 1-6 time altogether, as granule, makes 6 bags, can take altogether 2-5 days.
More than composition is by weight ratio, when producing, can increase or reduce according to corresponding proportion, can be unit with the kilogram as large-scale production, or be unit with the ton, it can milligram be unit also that bench-scale testing is produced, weight can increase or reduce, but the constant rate of the raw medicinal herbs weight proportion between each composition.
The proportioning of above weight obtains through science screening, for especial patient, and as serious symptom or light disease, fat or modest patient, the proportioning of the amount of can corresponding adjustment forming increases or reduces being no more than 300%, and drug effect is constant.
Single medicinal material, especially ministerial drug and adjuvant drug in more than forming also can be replaced by the suitable Chinese medicine with identical property of medicine, and its drug effect of the Chinese medicine preparation after the replacement is constant.
Pharmaceutical composition of the present invention, be to process through extraction or alternate manner by the medicine material that above-mentioned prescription is formed, make pharmaceutically active substance, subsequently, be raw material with this material, add the medicine acceptable carrier when needing, make according to the routine techniques of galenic pharmacy, described active substance can obtain by extracting plant drug material respectively, also can obtain by common extraction plant drug material, also can obtain by other means, as: pulverize, squeezing, calcining, grind, sieve, percolation, extraction, water is carried, alcohol extraction, fat is carried, methods such as chromatography obtain, these active substances can be the materials of extractum form, can be dry extract or fluid extract, make different concentration according to the different needs of preparation.
Pharmaceutically active substance in the pharmaceutical composition of the present invention, its percentage by weight shared in preparation can be 0.1-99.9%, all the other are the medicine acceptable carrier.Pharmaceutical composition of the present invention exists with the unit metering form, and described unit metering form refers to the unit of preparation, as every bag of medicinal tea, every of tablet, every of capsule, every bottle of oral liquid, every bag of granule etc.
Pharmaceutical composition of the present invention can be any pharmaceutically useful dosage form, and these dosage forms comprise medicinal tea, tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, cream, spray, drop, patch.Preparation of the present invention, peroral dosage form preferably is as medicinal tea, tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, powder etc.
Pharmaceutical composition of the present invention, the preparation of its oral administration can contain excipient commonly used, such as binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, flavoring agent and wetting agent, can carry out coating to tablet in case of necessity.
The filler that is suitable for comprises cellulose, mannitol, lactose and other similar filleies.Suitable disintegrating agent comprises starch, polyvinylpyrrolidone and starch derivatives, for example sodium starch glycollate.Suitable lubricant comprises magnesium stearate.The acceptable wetting agent of appropriate drug comprises sodium lauryl sulphate.
Can prepare solid oral composition by method commonly used such as mixing, filling, tabletting.Mix repeatedly active substance is distributed in those compositionss of a large amount of filleies of whole use.
The form of oral liquid for example can be aqueous or oily suspensions, solution, Emulsion, syrup or tincture, perhaps can be a kind of available water before use or other suitable composite dry products of carrier.This liquid preparation can contain conventional additive, such as suspending agent, for example sorbitol, syrup, methylcellulose, gelatin, hydroxyethyl-cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenation edible fat, emulsifying agent, for example lecithin, anhydro sorbitol-oleate or arabic gum, non-aqueous carrier (they can comprise edible oil), for example almond oil, fractionated coconut oil, propylene glycol or ethanol; Antiseptic, for example para hydroxybenzene methyl ester or p-Hydroxybenzoate or sorbitol, and if desired, can contain conventional flavouring agent or coloring agent.
For injection, the liquid unit dosage forms of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, this chemical compound can be suspended or dissolving.The preparation of solution is normally by being dissolved in active substance in a kind of carrier, and filter-sterilized before again it is packed into a kind of suitable bottle or the ampoule seals then.Adjuvant for example a kind of local anesthetic, antiseptic and buffer agent also can be dissolved in this carrier.In order to improve its stability, can be after the bottle of packing into that this compositions is freezing, and under vacuum, water is removed.
Pharmaceutical composition of the present invention, when being prepared into medicament, optionally add suitable medicine acceptable carrier, described medicine acceptable carrier is selected from: mannitol, sorbitol, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin C, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, alginate, gelatin, polyvinylpyrrolidone, glycerol, soil temperature 80, agar, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, the phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.
Pharmaceutical composition of the present invention is determined usage and dosage according to patient's situation in use, but obeys every day three times, each 1-20 agent, as: 1-20 bag or grain or sheet.
The invention will be further described by following specific embodiment, but not as limitation of the present invention.
The preparation of embodiment 1, pharmaceutical composition medicinal tea of the present invention
5 parts of Penthorum chinense, 5 parts of Ganodermas, 5 parts of Herba Moslaes, 5 parts of raw pearl barleys, 5 parts in Semen Armeniacae Amarum.
The described medicine of above prescription is ground into impalpable powder, crosses 200 mesh sieves, mix homogeneously, packing, sterilization, outer package, 4g/ pouch.
The preparation of embodiment 2, pharmaceutical composition medicinal tea of the present invention
60 parts of Penthorum chinense, 15 parts of Ganodermas, 10 parts of Herba Moslaes, 10 parts of raw pearl barleys, 10 parts in Semen Armeniacae Amarum.
The described medicine of above prescription is ground into impalpable powder, crosses 200 mesh sieves, mix homogeneously, packing, sterilization, outer package, 4g/ pouch.
The preparation of embodiment 3, pharmaceutical composition medicinal tea of the present invention
30 parts of Penthorum chinense, 10 parts of Ganodermas, 7 parts of Herba Moslaes, 7 parts of raw pearl barleys, 7 parts in Semen Armeniacae Amarum.
The described medicine of above prescription is ground into impalpable powder, crosses 200 mesh sieves, mix homogeneously, packing, sterilization, outer package, 4g/ pouch.
The preparation of embodiment 4, pharmaceutical composition medicinal tea of the present invention
45 parts of Penthorum chinense, 12 parts of Ganodermas, 8 parts of Herba Moslaes, 9 parts of raw pearl barleys, 8 parts in Semen Armeniacae Amarum.
The described medicine of above prescription is ground into impalpable powder, crosses 200 mesh sieves, mix homogeneously, packing, sterilization, outer package, 4g/ pouch.
The preparation of embodiment 5, pharmaceutical composition medicinal tea of the present invention
20 parts of Penthorum chinense, 8 parts of Ganodermas, 6 parts of Herba Moslaes, 6 parts of raw pearl barleys, 6 parts in Semen Armeniacae Amarum.
The described medicine of above prescription is ground into impalpable powder, crosses 200 mesh sieves, mix homogeneously, packing, sterilization, outer package, 4g/ pouch.
The preparation of embodiment 6, drug composition oral liquid of the present invention
30 parts of Penthorum chinense, 10 parts of Ganodermas, 7 parts of Herba Moslaes, 7 parts of raw pearl barleys, 7 parts in Semen Armeniacae Amarum, 7 parts of Radix Puerariaes, 7 parts of Flos puerariae lobataes.
A) distillation: with above-mentioned Herba Moslae, Semen Armeniacae Amarum two herbal medicine vapor distillations, collect volatile oil, distillate, medicinal residues, standby;
B) water extraction: medicinal residues and the described Penthorum chinense of present embodiment, Ganoderma, raw pearl barley, Radix Puerariae, Flos puerariae lobatae a) are put in the water extraction jar, the 6-10 times of water gaging that adds described pharmaceutical composition by weight, the best is 8 times of water gagings, decoct 2 times, each 1-4 hour, the best was 2 hours, boiling back steam pressure 0.03-0.04Mpa, collecting decoction filters;
C) concentrating: with distillate and the b in a) step) water extraction filtrate in the step puts in the concentration tank, and being concentrated into relative density is 1.01-1.03, and the best is 1.02, the clear paste that temperature is 50 ℃, thickening temperature 50-100 ℃;
D) precipitate with ethanol: concentrated solution is put in the Alcohol-settling tank, slowly adds 95% ethanol and makes it contain alcohol amount to reach 50%-75%, and the best is 65%, after fully stirring, leaves standstill 8-20 hour, and the best is 12 hours, filters;
E) reclaim ethanol: filtrate is put in the reclaim under reduced pressure jar, decompression recycling ethanol, and being concentrated into relative density is 1.04-1.07, and the best is 1.05-1.06, and the thick paste that temperature is 45 ℃, gets water extract by thickening temperature 40-100 ℃.
F) preparation of oral liquid: add the volatile oil in a) step in the water extract, stir, add water to relative density and be about 1.01-1.05, the best is 1.03-1.04, stirs evenly, and fill, sterilization namely gets oral liquid.
The preparation of embodiment 7, drug composition oral liquid of the present invention
10 parts of Penthorum chinense, 7 parts of Ganodermas, 6 parts of Herba Moslaes, 6 parts of raw pearl barleys, 6 parts in Semen Armeniacae Amarum, 6 parts of Radix Puerariaes, 6 parts of Flos puerariae lobataes.
Make oral liquid according to embodiment 6 described preparation methoies.
The preparation of embodiment 8, drug composition oral liquid of the present invention
50 parts of Penthorum chinense, 12 parts of Ganodermas, 8 parts of Herba Moslaes, 10 parts of raw pearl barleys, 8 parts in Semen Armeniacae Amarum, 8 parts of Radix Puerariaes, 10 parts of Flos puerariae lobataes.
Make oral liquid according to embodiment 6 described preparation methoies.
The preparation of embodiment 9, medicament composition capsule agent of the present invention
30 parts of Penthorum chinense, 10 parts of Ganodermas, 7 parts of Herba Moslaes, 7 parts of raw pearl barleys, 7 parts in Semen Armeniacae Amarum, 7 parts of Fructus Amomis.
A) distillation: with above-mentioned Herba Moslae, Semen Armeniacae Amarum two herbal medicine vapor distillations, collect volatile oil, distillate, medicinal residues, standby;
B) water extraction: medicinal residues and the described Penthorum chinense of present embodiment, Ganoderma, raw pearl barley, Fructus Amomi a) are put in the water extraction jar, the 6-10 times of water gaging that adds described pharmaceutical composition by weight, the best is 8 times of water gagings, decoct 2 times, each 1-4 hour, the best was 2 hours, boiling back steam pressure 0.03-0.04Mpa, collecting decoction filters;
C) concentrating: with distillate and the b in a) step) water extraction filtrate in the step puts in the concentration tank, and being concentrated into relative density is 1.01-1.03, and the best is 1.02, the clear paste that temperature is 50 ℃, thickening temperature 50-100 ℃;
D) precipitate with ethanol: concentrated solution is put in the Alcohol-settling tank, slowly adds 95% ethanol and makes it contain alcohol amount to reach 50%-75%, and the best is 65%, after fully stirring, leaves standstill 8-20 hour, and the best is 12 hours, filters;
E) reclaim ethanol: filtrate is put in the reclaim under reduced pressure jar, decompression recycling ethanol, and being concentrated into relative density is 1.04-1.07, and the best is 1.05-1.06, and the thick paste that temperature is 45 ℃, gets water extract by thickening temperature 40-100 ℃.
F) preparation of capsule:
A ') with e) water extract in the step is tiled in the vacuum drying oven vacuum drying.Vacuum-0.06～-0.09Mpa, temperature 40-100 ℃, get dry extract;
B ') dried cream powder is broken into fine powder 80-120 order;
C ') dried cream powder is blended into an amount of dextrin, sieve, and mix homogeneously, incorporation time 10-50 minute, the best was 30 minutes;
D ') mixed dried cream powder 95% alcohol granulation was granulated time 3-10 minute, and the best granulation time is 7 minutes;
E ') with d ') in made wet granular be tiled in the drying baker drying, shop layer thickness about 1-4cm, the about 2cm of the best, baking temperature 50-100 ℃;
F ') with dried granule granulate, be 14 purpose screen cloth granulate with the order number, spray into the volatile oil in a) step, mix homogeneously;
G ') encapsulated, every capsules dress 0.3-0.5g;
The preparation of embodiment 10, medicament composition capsule agent of the present invention
60 parts of Penthorum chinense, 12 parts of Ganodermas, 8 parts of Herba Moslaes, 8 parts of raw pearl barleys, 8 parts in Semen Armeniacae Amarum, 10 parts of Fructus Amomis.
Make capsule according to embodiment 9 described preparation methoies.
The preparation of embodiment 11, medicament composition capsule agent of the present invention
15 parts of Penthorum chinense, 7 parts of Ganodermas, 6 parts of Herba Moslaes, 6 parts of raw pearl barleys, 6 parts in Semen Armeniacae Amarum, 6 parts of Fructus Amomis.
Make capsule according to embodiment 9 described preparation methoies.
The preparation of embodiment 12, pharmaceutical composition tablet of the present invention
30 parts of Penthorum chinense, 10 parts of Ganodermas, 7 parts of Herba Moslaes, 7 parts of raw pearl barleys, 7 parts in Semen Armeniacae Amarum, 7 parts of Semen Myristicaes.
A) distillation: with above-mentioned Herba Moslae, Semen Armeniacae Amarum, Semen Myristicae three herbal medicine vapor distillations, collect volatile oil, distillate, medicinal residues, standby;
B) water extraction: medicinal residues and the described Penthorum chinense of present embodiment, Ganoderma, raw pearl barley a) are put in the water extraction jar, the 6-10 times of water gaging that adds described pharmaceutical composition by weight, the best is 8 times of water gagings, decoct 2 times, each 1-4 hour, the best was 2 hours, boiling back steam pressure 0.03-0.04Mpa, collecting decoction filters;
C) concentrating: with distillate and the b in a) step) water extraction filtrate in the step puts in the concentration tank, and being concentrated into relative density is 1.01-1.03, and the best is 1.02, the clear paste that temperature is 50 ℃, thickening temperature 50-100 ℃;
D) precipitate with ethanol: concentrated solution is put in the Alcohol-settling tank, slowly adds 95% ethanol and makes it contain alcohol amount to reach 50%-75%, and the best is 65%, after fully stirring, leaves standstill 8-20 hour, and the best is 12 hours, filters;
E) reclaim ethanol: filtrate is put in the reclaim under reduced pressure jar, decompression recycling ethanol, and being concentrated into relative density is 1.04-1.07, and the best is 1.05-1.06, and the thick paste that temperature is 45 ℃, gets water extract by thickening temperature 40-100 ℃.
F) preparation of tablet:
A ') with e) water extract in the step is tiled in the vacuum drying oven vacuum drying.Vacuum-0.06～-0.09Mpa, temperature 40-100 ℃, get dry extract;
B ') dried cream powder is broken into fine powder 80-120 order;
C ') dried cream powder is blended into an amount of dextrin, sprays into the volatile oil in a) step, sieve, and mix homogeneously, incorporation time 10-50 minute, the best was 30 minutes;
D ') makes tablet, every heavy 0.3-0.5g;
The preparation of embodiment 13, pharmaceutical composition tablet of the present invention
60 parts of Penthorum chinense, 15 parts of Ganodermas, 8 parts of Herba Moslaes, 8 parts of raw pearl barleys, 8 parts in Semen Armeniacae Amarum, 10 parts of Semen Myristicaes.
Make tablet according to embodiment 12 described preparation methoies.
The preparation of embodiment 14, pharmaceutical composition tablet of the present invention
10 parts of Penthorum chinense, 6 parts of Ganodermas, 5 parts of Herba Moslaes, 5 parts of raw pearl barleys, 5 parts in Semen Armeniacae Amarum, 5 parts of Semen Myristicaes.
Make tablet according to embodiment 12 described preparation methoies.
The preparation of embodiment 15, medicament composition granule agent of the present invention
30 parts of Penthorum chinense, 10 parts of Ganodermas, 7 parts of Herba Moslaes, 7 parts of raw pearl barleys, 7 parts in Semen Armeniacae Amarum
A) distillation: with above-mentioned Herba Moslae, Semen Armeniacae Amarum two herbal medicine vapor distillations, collect volatile oil, distillate, medicinal residues, standby;
B) water extraction: the medicinal residues in a) and above-mentioned Penthorum chinense, Ganoderma, raw pearl barley are put in the water extraction jar, the 6-10 times of water gaging that adds described pharmaceutical composition by weight, the best is 8 times of water gagings, decoct 2 times, each 1-4 hour, the best was 2 hours, boiling back steam pressure 0.03-0.04Mpa, collecting decoction filters;
C) concentrating: with distillate and the b in a) step) water extraction filtrate in the step puts in the concentration tank, and being concentrated into relative density is 1.01-1.03, and the best is 1.02, the clear paste that temperature is 50 ℃, thickening temperature 50-100 ℃;
D) precipitate with ethanol: concentrated solution is put in the Alcohol-settling tank, slowly adds 95% ethanol and makes it contain alcohol amount to reach 50%-75%, and the best is 65%, after fully stirring, leaves standstill 8-20 hour, and the best is 12 hours, filters;
E) reclaim ethanol: filtrate is put in the reclaim under reduced pressure jar, decompression recycling ethanol, and being concentrated into relative density is 1.04-1.07, and the best is 1.05-1.06, and the thick paste that temperature is 45 ℃, gets water extract by thickening temperature 40-100 ℃.
F) preparation of granule:
A ') with e) water extract in the step is tiled in the vacuum drying oven vacuum drying.Vacuum-0.06～-0.09Mpa, temperature 40-100 ℃, get dry extract;
B ') dried cream powder is broken into impalpable powder, crosses 200 mesh sieves;
C ') dried cream powder is blended into an amount of dextrin, sieve, and mix homogeneously, incorporation time 10-50 minute, the best was 30 minutes;
D ') mixed dried cream powder 95% alcohol granulation was granulated time 3-10 minute, and the best granulation time is 7 minutes;
E ') with d ') in made wet granular be tiled in the drying baker drying, shop layer thickness about 1-4cm, the about 2cm of the best, baking temperature 50-100 ℃;
F ') with dried granule granulate, be 14 purpose screen cloth granulate with the order number, spray into the volatile oil in a) step, mix homogeneously;
G ') pack, every packed 0.3-0.5g;
The preparation of embodiment 16, medicament composition granule agent of the present invention
55 parts of Penthorum chinense, 5 parts of Ganodermas, 5 parts of Herba Moslaes, 5 parts of raw pearl barleys, 5 parts in Semen Armeniacae Amarum
Make granule according to embodiment 15 described preparation methoies.
The preparation of embodiment 17, medicament composition granule agent of the present invention
10 parts of Penthorum chinense, 15 parts of Ganodermas, 10 parts of Herba Moslaes, 10 parts of raw pearl barleys, 10 parts in Semen Armeniacae Amarum
Make granule according to embodiment 15 described preparation methoies.
The preparation of embodiment 18, medicament composition granule agent of the present invention
60 parts of Penthorum chinense, 15 parts of Ganodermas, 5 parts of Herba Moslaes, 5 parts of raw pearl barleys, 5 parts in Semen Armeniacae Amarum
Make granule according to embodiment 15 described preparation methoies.
The preparation of embodiment 19, medicament composition granule agent of the present invention
5 parts of Penthorum chinense, 5 parts of Ganodermas, 10 parts of Herba Moslaes, 10 parts of raw pearl barleys, 10 parts in Semen Armeniacae Amarum
Make granule according to embodiment 15 described preparation methoies.
More than be optimum implementation with embodiment 3,6,9,12,15
Further specify the therapeutic effect of pharmaceutical composition of the present invention by following experiment.
1. material and method:
1.1 material and instrument
Body weight is 75 of the SPF level SD rats (purchasing white Academy of Military Medicine, PLA laboratory, animal licence: SCXK-(army) 2007-004) of 180 ± 20g; The high nutrient fodder of high fat (available from radiological study institute of Chinese Academy of Sciences animal center) proportioning: 1% cholesterol, 8% yolk powder, 0.3% sodium cholate, 10% Adeps Sus domestica, 80.7% normal feedstuff; 56 ° of cattle pen mountain strong, colourless liquor distilled from sorghum (Beijing Shunxin Agriculture Co., Ltd. Niulanshan Winery's production); HE dyestuff (Tianjin University Of Traditional Chinese Medicine's Pathology Lab preparation); Aspartate amino transferase (AST) and alanine aminotransferase (ALT) are measured test kit (the middle north of giving birth to controls 201205); Triglyceride (TG) and cholesterol (CHO) are measured test kit (giving birth to north control 201205,201204 in being respectively); Xanthine oxidase (XO) and malonaldehyde (MDA) are measured test kit (Nanjing builds up 20120718); PDGF measures test kit; Centrifuge (the vigorous LDZ5-2 type of Beijing thunder); Semi-automatic biochemical analyzer (microlab300, Dutch figure prestige); Spectrophotometer (Shanghai 722RS type).
1.2. method
1.2.1 the foundation of animal model
Adopt the ethanol administration by gavage to set up the alcoholic fatty liver model, 75 ripe SD male rats of SPF level are raised (common normal feedstuff through all adaptabilities, ad lib drinking-water, a small amount of normal saline filling stomach) is divided into 3 groups at random after, be matched group (n=25), Chinese drug-treated group (n=20), Western medicine group (n=30).(sooner or later more than the time phase difference 8h) gives 1.5ml/100g ethanol filling stomach by recording body weight weekly 2 times daily in morning and evening, the ethanol volume fraction is from the beginning of being 40% (4.8g.kg-1.d-1) and continuing to for the 4th weekend, the back increases ethanol volume fraction to 45% (5.4g.kg-1.d-1) to the 8th weekend, keep volume fraction when the ethanol volume fraction adds as 50% (6.0g.kg-1.d-1) and do not fade to experiment end (in 12 weeks of Therapy lasted, adaptability is raised and is not counted in experiment week).
1.2.2 administration situation and drawing materials
Each group is all on above alcoholic fatty liver modeling basis; it is constant all in the 9th that Chinese medicine, Western medicine and model group ethanol are irritated stomach; the 1st time ethanol is irritated stomach after half an hour; Chinese drug-treated group is given this pharmaceutical composition 2ml (concentration 1.33g/ml) and is irritated stomach; Western medicine gives Essentiale N/Essentiale Forte N suspension 2ml (polyenoid phosphate ester choline concentration 4.56mg/ml) and irritates stomach, and matched group gives isodose normal saline 2ml and irritates stomach.
Since during rats death more, test the 10th week 2 ethanol and irritate stomach and be kept to 1 time to the experiment end.Each is all raised with the high nutrient fodder of high fat during organizing rat experiment, ad lib drinking-water.
Control rats is respectively at 4 of the 4th all picked at random, 5 of the 8th all picked at random, fasting water was weighed after 12 hours, the etherization eye socket is got blood, take off and namely take out liver after neck is put to death, title liver weight in wet base is also got right lobe of the liver and is fixed with 10% formalin, and section is with paraffin embedding, and HE dyeing back is in the descending pathological observation of light microscopic.
Testing all the other respectively organizes rat and draws materials for the 12nd weekend, weigh behind the fasting water 12h, etherization posterior orbit sample of blood, drawn 2ml, take off and namely take out liver after neck is put to death, title liver weight in wet base is also got right lobe of the liver and is fixed with 10% formalin, section is with paraffin embedding, and HE dyeing back is in the descending pathological observation of light microscopic, and left liver leaf is got about 1 * 1cm hepatic tissue blocking and deposited in-70 ℃ of refrigerator backups with the tinfoil parcel.The whole blood sample is used for measuring biochemical zymetology index and ELISA detection through 3000r/min centrifuging and taking serum.
1.2.3 observation index and assay method
1.2.3.1 animal performance
Comprise mental status, fur, mobility, feed situation, defecation and contamination situation, and survey body weight weekly 2 times.
1.2.3.2 perusal
Comprise profile, size, color and luster, quality, the edge situation of liver and weigh.
1.2.3.3 biochemical indicator is measured
Measure rat ALT, AST, TG, TC index.
1.2.3.4 ELISA measures
Measure the PDGF-bb vigor.
1.2.3.5 pathological observation
Paraffin embedding, the pathological change (hepatocellular degeneration, necrosis, cell infiltration etc.) of rat liver is observed in HE dyeing back, judges steatosis degree and alcoholic hepatitis inflammation mobility according to " 2010 editions alcoholic liver disease practice guidelines " standard.
1.3 statistical procedures
Use the SPSS18.0 common software and analyze, experimental data with
± S represents, adopts variance analysis and rank test.
2. result
2.1 ordinary circumstance
Each experimental group rat all ethanol irritate stomach after 15 minutes the lighter walk shakiness, walking mops floor, weight person's eyeball congestion, drowsiness, return to normal behind about 5h, and engender lethargy around the after irritating stomach, the hair luster degree is poor, movable less, Chinese drug-treated group rat soft partially color depth of stool after giving Chinese medicine to irritate stomach is black, and all the other group rats are hard and dry, and the control rats food-intake is few than Chinese drug-treated group and Western medicine group, lethargy, activity are still less.
Table 1 is respectively organized rat body weight, liver index (liver wet weights/rat weight * 100%), the contrast of liver weight in wet base
Annotate: because of experimental implementation and rat digestive tract damage problem, respectively organizing rat in the experimentation all has death, dead 4 of control rats, and the Chinese drug-treated group death toll is 5, dead 11 altogether of Western medicine groups.
From body weight; overall comparing difference has statistical significance (P=0.000); 4W group and 12W group and in, the Western medicine group; 8W group and 12W group and in, Western medicine group difference has statistical significance (P is 0.000); progress and high lipid food intake accumulation in time; rat body weight continues to increase; as seen from Table 1; Chinese drug-treated group and Western medicine group body weight are apparently higher than control rats; the Chinese drug-treated group body weight is the highest, show that pharmaceutical intervention alleviates the rat liver damage to a certain extent, and protection rat digestive tract changes; promote appetite, thus weight increase.
From the liver index, adopt the overall P value of variance analysis＜0.05, but compare zero difference between group, liver weight in wet base comparing difference meaningless (P＞0.05) between each group.
2.2 perusal
The normal liver color dimness of control rats liver color and luster, pale brown color or bronzing, quality are hard partially, tunicle and surrounding tissue adhesion, the edge is blunt slightly; Chinese drug-treated group rat liver color and luster is shallow than matched group, is bronzing, and quality is soft slightly, and liver tunicle and surrounding tissue have slight adhesion, and the edge is blunt slightly; Western medicine group rat liver color and luster is close than Chinese drug-treated group, is bronzing, and quality is soft slightly, and liver tunicle and surrounding tissue have adhesion, and the edge is blunt.
2.3 the mensuration of biochemical indicator
Table 2
(1) from ALT, each group difference has statistical significance (P=0.001＜0.05).Group difference shows as between Chinese drug-treated group and the matched group 12W, and difference has statistical significance (P all＜0.05, P is 0.001), and Chinese drug-treated group hepatic injury degree is starkly lower than matched group 12W, Western medicine group, and it is the most obvious that Chinese drug-treated group is intervened the hepatic injury degree.
(2) from AST, Chinese drug-treated group and matched group and Western medicine group difference all have statistical significance (P all＜0.05 are respectively (0.002,0.015), and the hepatic injury degree obviously alleviates.
(3) from TG, each group difference has statistical significance (P=0.001＜0.05).Group difference shows as between matched group 12W and Chinese drug-treated group, the Western medicine group and between Western medicine group and the Chinese drug-treated group, and difference all has statistical significance, and (P all＜0.05, be respectively 0.000,0.011,0.03), expression Western medicine group, 2 groups of medicines of Chinese drug-treated group all have positive effect, and according to average relatively, the Chinese drug-treated group effect is best.
(4) from TC, each group difference has statistical significance (P=0.001＜0.05).1. group difference shows as between matched group 8W and matched group 12W, Western medicine group, the Chinese drug-treated group, and difference all has statistical significance (P all＜0.05 is respectively 0.004,0.001,0.000); 2. between matched group 4W and the Chinese drug-treated group, and difference all has statistical significance (P=0.007＜0.05); 3. between Chinese drug-treated group and the Western medicine group, and difference all has statistical significance (P=0.007＜0.05).Illustrate that Western medicine group, Chinese drug-treated group medicine all have positive effect, and according to average relatively, the Chinese drug-treated group effect is best, the Western medicine group is taken second place, but difference not statistically significant (P=0.153＞0.05) between Chinese drug-treated group and the Western medicine group.
When hepatocyte injury, ALT and AST namely overflow in cell, are released into blood.Serum alt and AST are active to raise, and has reflected the hepatocyte extent of damage to a certain extent.As can be seen from Table 2; the ALT of different time sections matched group and AST activity all are higher than Chinese drug-treated group and Western medicine group; prompting matched group hepatic injury degree is more serious, and this pharmaceutical composition and Western medicine Essentiale N/Essentiale Forte N can reduce ALT, AST activity, and the hepatic injury that ethanol is caused plays a protective role.TG, each group of TC is all variant, and when the fat of the long-term huge uptake of gastrointestinal tract exceeded the consumption of body heat, intrahepatic fat discharged excessive unesterified fatty acid (NEFA).NEFA is the predecessor of TG, and its increase causes synthetic TG increase in the liver.If the speed of synthetic TG has surpassed when being combined as very low density lipoprotein (VLDL) and being secreted into the speed of blood flow in the liver, the accumulation of TG in the liver has just appearred, and the TG value of new drug group is minimum, may be relevant with the release that reduces unesterified fatty acid.
Can find out the variation tendency that each zymetology index of matched group different time sections descends after occurring rising then, the 4th thoughtful the 8th week from table 2, AST and ALT all obviously raise, it is more serious that ethanol is irritated the stomach earlier damage, immunologic tolerance may occur, and its mechanism awaits further research.
2.4 hepatic tissue MDA, XO activity and ELISA measure blood-serum P DGF-bb vitality test.
Table 3
The equal not statistically significant of each group difference of hepatic tissue MDA (P=0.219＞0.05).
The equal not statistically significant of each group difference of hepatic tissue XO (P=0.125＞0.05).
The equal not statistically significant of each group difference of blood-serum P DGF (P=0.502＞0.05).
MDA content can be understood the degree of body lipid peroxidation in the mensuration blood liver tissue homogenate; for research hepatic injury be a significant index; as can be seen from Table 3; change not remarkable between each group; but Chinese drug-treated group and Western medicine group all are higher than matched group; show that pharmaceutical intervention can suppress lipid peroxidation; the liver protecting is impaired; xanthine oxidase is one of sensitive indicator of alcoholic liver injury; the height of its activity reflects the hepar damnification degree; liver damage is more serious, and activity is more high, and the matched group activity is higher than the Chinese medicine and western medicine group in this experiment; the prompting damage is heavy than the medicine group; medicine reduces hepatic injury to a certain extent, but a little higher than Western medicine group of Chinese drug-treated group, the lower reason of concentration in may testing.Though PDGF numerical value not statistically significant, Chinese drug-treated group PDGF is minimum as can be seen, and Chinese medicine is being better than the Western medicine group aspect the reduction platelet growth derivative factor activity.
2.5 pathological observation
2.5.1 Chinese drug-treated group
The structural change of new drug group lobules of liver, the hepatocyte border is fuzzy slightly, and the diffusivity hydropic degeneration is obvious, occurs obviously some kitchen range shape necrosis and cell debris around the central vein, and fatty range degree is (F2-3 level) obviously, and erythrocyte accumulation phenomena between tissue appears in the part specimen.
2.5.2 Western medicine group
The structural change of Western medicine group lobules of liver, the hepatocyte border is fuzzy slightly, the diffusivity hydropic degeneration is more obvious, significantly some kitchen range shape necrosis and cell debris companion portal area cell infiltration appear around the central vein, steatosis and Chinese drug-treated group difference are little, and majority is slight steatosis (F1-2 level), do not observe tangible fat and become (F3 and more than), erythrocyte accumulation phenomena between tissue appears in indivedual specimen, and its reason remains further to be investigated.
2.5.3 matched group
Matched group 4 pericyte's edema are more obvious, 8 all its hydropic degenerations further increase the weight of, part of hepatocytes is the balloon sample and becomes, visible clastic necrocytosis around the central vein, 12 all leaflet structures change, the hepatocyte obscure boundary, point kitchen range shape necrosis and cell debris still poly combine in around the central vein, and lipid droplet appears, and steatosis is obvious slightly than other groups, large tracts of land fat vacuole (F3 level) appears in the part specimen, and indivedual specimen the slight hypertrophy of fibrosis occurs and grow in the lobules of liver and erythrocyte accumulation phenomena between tissue.
On overall variation tendency, the steatosis of matched group is in lasting state of progress, the steatosis of Chinese drug-treated group and Western medicine group is light and change not obvious than matched group, but cellular edema is more obvious, it is obvious than Chinese drug-treated group to put the necrosis of kitchen range shape and cell debris companion portal area cell infiltration around its Chinese medicine and western medicine group central vein, cellular control unit is visible significantly cell hydropic degeneration also, part is the balloon sample and becomes, the portal area neutrophil infiltration, the many places necrosis region, consider to take place and exist acute injury, the necrosis of some kitchen range shape is along with the ethanol stimulation time prolongs, the diffusivity hydropic degeneration appears, point kitchen range shape necrosis region increases, and the portal area cell infiltration increases the weight of, and hepatic injury is and increases the weight of trend.
The toxicity test of this pharmaceutical composition
1, acute toxicity test:
Pharmaceutical composition extractum is pressed 100g/kg and is given the mouse stomach administration, does not have dead the generation, does not see movable unusual.Be equivalent to 3 times/day of clinical consumption, 4g/ time, everyone presses more than 800 times that 50kg calculates.Pharmaceutical composition extractum is pressed 60g/kg and is given the rat oral gavage administration, does not have dead the generation, does not also see movable unusual.Be equivalent to more than 400 times of clinical consumption.
2, long term toxicity test:
Pharmaceutical composition extractum with 36,16,8g/Kg/ day give the continuous gastric infusion of rat 3 months, hematological indices is not had obvious influence; Blood parameters also there is not obvious influence; Organ coefficient, histopathologic examination also do not find tangible pathological change.
Below the clinical practice with above-mentioned medicine composite for curing alcoholic fatty liver is illustrated.
By implementing the clinical trial protocol of State Food and Drug Administration's reply, carried out uncomfortable in chest to the alcohol fatty hepatopath, hypochondriac pain, dizzy, breathe hard, facial dark violet, fatigue and weak, the tcm syndrome integration, the tcm syndrome single index, total effects, the tcm syndrome curative effect, onset time, antiviral, the antibacterial clinical observation that waits item, compare with this pharmaceutical composition and contrast medicine Essentiale N/Essentiale Forte N in the research, therapeutic evaluation standard according to the current international practice is estimated it, and the result shows that this pharmaceutical composition is the effective and safe endo-medicine preparation for the treatment of alcoholic fatty liver.
Adopt randomized, double-blind layering counter point, clinical observation alcohol fatty hepatopath 132 examples, wherein 70 examples are organized in treatment, with the each 4g of this drug composition, take 3 months every day 3 times, and matched group 62 examples are taken Essentiale N/Essentiale Forte N, and each 5mg, took 3 months at every day 2 times.Observe that the patient is uncomfortable in chest, hypochondriac pain, dizziness, breathe hard, situation of change before and after the treatment of facial dark violet, fatigue and weak, comprehensive function and body of the tongue, tongue fur, all index of pulse condition, the result shows:
1, returned to after patient's treatment uncomfortable in chest 0 fen and 1 fen person is 61 examples, account for 87%; Returned to 0 fen after the hypochondriac pain treatment and 1 fen person is 60 examples, account for 85.7%; Returning to the 0-2 person of branch after the dizzy treatment is 62 examples, accounts for 88.6%; Breathe hard and return to the 0-2 person of branch and account for 82% after the treatment; Return to the 0-2 person of branch after the facial purple dark treatment and account for 78%; Return to the 0-2 person of branch after the fatigue and weak treatment and account for 83.0%;
2, before and after the treatment patient comprehensive function level relatively, returning to 0-2 behind patient's comprehensive function horizontal stretcher, to divide horizontal person be 80%;
3, patient's picture of the tongue, pulse condition integration relatively have significance to recover after body of the tongue, tongue fur and the pulse condition three card treatments before and after the treatment, and especially picture of the tongue recovers very good;
4, treatment back patient's total effects compares, and the total effective rate after the treatment is 91.3%, and obvious effective rate is 82%;
5, the total effective rate after treatment back patient's tcm syndrome curative effect is relatively treated is 97.1%, and cure-remarkable-effectiveness rate is 80%;
6, treatment back patient's treatment group and matched group tcm syndrome curative effect relatively see Table 1:
Table 1 liang group treatment back traditional Chinese medical science disease total effective rate curative effect is [example (%)] relatively
Untoward reaction does not all take place in the therapeutic process and after the treatment in 7, patient safety index there was no significant difference (P＞0.05) before and after the treatment.
More than every index and matched group relatively, every index and the clinical efficacy of this pharmaceutical composition all are better than contrasting medicine, the every index for the treatment of back patient obviously is better than similar medicine with the doing well,improving situation.
8, the described medicine composite for curing alcoholic fatty liver of this description model case one example:
The patient: the Meng, the man, 52 years old, people from Hongqiao, Tianjin, main cause " hypochondriac pain, fatigue and weak 3 days ", on August 9th, 2012 was admitted to hospital.
Hypochondriac pain, fatigue and weak appearred in the patient before 3 days, uncomfortable in chest, dizzy, breathe hard, the symptom of facial alcoholic fatty liver such as dark violet, greasy fur, the right heavy left string of arteries and veins.Lab testing: ALT:212U/L, AST:278U/L, MDA:4.36umol/L, XO:21.54umol/L, PDGF:48.98umol/L, TG:0.98umol/L, TC:3.41umol/L.
Diagnosis:
Tcm diagnosis: stagnation of QI due to depression of the liver, accumulate in the turbid damp
Western medicine diagnose: alcoholic fatty liver
Treatment:
With ascending the clear and descending the turbid resolving depression method
Side's medicine:
Used the described medicine composite for curing of this description 3 months, hypochondriac pain disappears, and fatigue and weak disappears substantially, and transference cure uncomfortable in chest, dizzy is breathed hard and significantly taken a turn for the better, and facially purplely secretly obviously changes ruddy, pale tongue with white fur, and pulse condition is gentle, and spirit, diet, two are just normal.Lab testing: ALT:44U/L, AST:47U/L, MDA:264umol/L, XO:12.38umol/L, PDGF:24.63umol/L, TG:0.44umol/L, TC:1.97umol/L.
Claims (10)
1. pharmaceutical composition of preventing and treating alcoholic fatty liver, it is characterized in that: described pharmaceutical composition is made by following flavour of a drug by weight, Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part.
2. pharmaceutical composition according to claim 1, it is characterized in that: can also add the Chinese medicine Fructus Amomi in the described pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Fructus Amomi 5-10 part.
3. pharmaceutical composition according to claim 1, it is characterized in that: can also add the Chinese medicine Semen Myristicae in the described pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Semen Myristicae 5-10 part.
4. pharmaceutical composition according to claim 1, it is characterized in that: can also add Radix Puerariae, Flos puerariae lobatae in the described pharmaceutical composition prescription, the prescription that obtains is Penthorum chinense 5-60 part, Ganoderma 5-15 part, Herba Moslae 5-10 part, raw pearl barley 5-10 part, Semen Armeniacae Amarum 5-10 part, Radix Puerariae 5-10 part, Flos puerariae lobatae 5-10 part.
5. according to any described pharmaceutical composition of claim 1-4, it is characterized in that described pharmaceutical composition reduces the accumulation of TG in the liver by reducing the release of unesterified fatty acid, increases lipid metabolism, thus the control alcoholic fatty liver.
6. according to any described pharmaceutical composition of claim 1-4, it is characterized in that described pharmaceutical composition alleviates lipid peroxidation by class antioxidant sample effectiveness, alleviates hepatic fibrosis, thus the control alcoholic fatty liver.
7. according to any described pharmaceutical composition of claim 1-4, it is characterized in that, described pharmaceutical composition is by reducing platelet growth derivative factor (PDGF) vigor, suppress HSC and activate conversion, prevent that alcoholic fatty liver from developing to alcoholic fibrosis, thus the control alcoholic fatty liver.
8. according to any described pharmaceutical composition of claim 1-4, it is characterized in that described pharmaceutical composition is by reducing ALT, AST activity, the hepatic injury that ethanol is caused plays a protective role, thus the control alcoholic fatty liver.
9. according to any described pharmaceutical composition of claim 1-4, it is characterized in that described pharmaceutical composition is beneficial to hepatocellular energy metabolism by suppressing xanthine oxidase XO activity, thus the control alcoholic fatty liver.
10. preparation of drug combination method of preventing and treating alcoholic fatty liver, this method comprises the steps:
A) distillation: require Herba Moslae, Semen Armeniacae Amarum or Herba Moslae, Semen Armeniacae Amarum, Semen Myristicae two in any described pharmaceutical composition of 1-4 to distinguish the flavor of or three herbal medicine vapor distillations aforesaid right, collect volatile oil, distillate, medicinal residues, standby;
B) water extraction: all the other medicines except Herba Moslae, Semen Armeniacae Amarum or Herba Moslae, Semen Armeniacae Amarum, Semen Myristicae in the medicinal residues in a) and any described pharmaceutical composition of aforesaid right requirement 1-4 are put in the water extraction jar, the 6-10 times of water gaging that adds described pharmaceutical composition by weight, decoct 2 times, each 1-4 hour, boiling back steam pressure 0.03-0.04Mpa, collecting decoction filters;
C) concentrating: with distillate and the b in a) step) water extraction filtrate in the step puts in the concentration tank, and being concentrated into relative density is 1.01-1.03, the clear paste that temperature is 50 ℃, thickening temperature 50-100 ℃;
D) precipitate with ethanol: concentrated solution is put in the Alcohol-settling tank, slowly adds 95% ethanol and makes it contain alcohol amount to reach 50%-75%, after fully stirring, left standstill 8-20 hour, filter;
E) reclaim ethanol: filtrate is put in the reclaim under reduced pressure jar, decompression recycling ethanol, and being concentrated into relative density is 1.04-1.07, the thick paste that temperature is 45 ℃, gets water extract by thickening temperature 40-100 ℃.
F) preparation of granule:
A ') with e) water extract in the step is tiled in vacuum drying in the vacuum drying oven, vacuum-0.06～-0.09Mpa, temperature 40-100 ℃, get dry extract;
B ') dried cream powder is broken into impalpable powder, crosses 200 mesh sieves;
C ') dried cream powder is blended into an amount of dextrin, sieves mix homogeneously, incorporation time 10-50 minute;
D ') mixed dried cream powder 95% alcohol granulation was granulated time 3-10 minute;
E ') with d ') in made wet granular be tiled in the drying baker dry, shop layer thickness 1-4cm, baking temperature 50-100 ℃;
F ') with dried granule granulate, be 14 purpose screen cloth granulate with the order number, spray into the volatile oil of collecting in a) step, mix homogeneously;
G ') pack, every packed 0.3-0.5g.
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| CN103829008A (en) * | 2014-02-11 | 2014-06-04 | 陆开云 | Dioscorea alata milk tea sesame cake and preparation method thereof |
| CN108066373A (en) * | 2018-01-10 | 2018-05-25 | 高山 | A kind of drug and preparation method for preventing diabetes B |
| CN116688064A (en) * | 2023-06-28 | 2023-09-05 | 山东中医药大学 | Traditional Chinese medicine composition for preventing alcoholic fatty liver and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732369A (en) * | 2008-11-06 | 2010-06-16 | 四川科伦新光医药有限公司 | Novel application of penthorum chinense pursh extract |
| CN102488850A (en) * | 2011-12-31 | 2012-06-13 | 黄文珍 | Traditional Chinese medicinal composition for treating alcoholic fatty liver and preparation method thereof |
| CN102860516A (en) * | 2012-10-22 | 2013-01-09 | 纪显玥 | Liver protection, stomach invigorating anti-alcoholic Chinese medicine healthcare food and preparation method thereof |
-
2013
- 2013-06-24 CN CN201310251077.1A patent/CN103272146B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732369A (en) * | 2008-11-06 | 2010-06-16 | 四川科伦新光医药有限公司 | Novel application of penthorum chinense pursh extract |
| CN102488850A (en) * | 2011-12-31 | 2012-06-13 | 黄文珍 | Traditional Chinese medicinal composition for treating alcoholic fatty liver and preparation method thereof |
| CN102860516A (en) * | 2012-10-22 | 2013-01-09 | 纪显玥 | Liver protection, stomach invigorating anti-alcoholic Chinese medicine healthcare food and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 袁叶飞等: "赶黄草提取物对大鼠酒精性脂肪肝的保护作用研究", 《中国药房》, vol. 23, no. 11, 31 December 2012 (2012-12-31), pages 976 - 978 * |
| 韩素恒等: "中药复方治疗酒精性脂肪肝研究进展", 《陕西中医》, vol. 33, no. 5, 31 December 2012 (2012-12-31), pages 632 - 634 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103829008A (en) * | 2014-02-11 | 2014-06-04 | 陆开云 | Dioscorea alata milk tea sesame cake and preparation method thereof |
| CN108066373A (en) * | 2018-01-10 | 2018-05-25 | 高山 | A kind of drug and preparation method for preventing diabetes B |
| CN116688064A (en) * | 2023-06-28 | 2023-09-05 | 山东中医药大学 | Traditional Chinese medicine composition for preventing alcoholic fatty liver and preparation method and application thereof |
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| CN103272146B (en) | 2014-11-19 |
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