CN1191082C

CN1191082C - Chinese medicinal composition for treating fatty liver and its preparation method

Info

Publication number: CN1191082C
Application number: CNB021590796A
Authority: CN
Inventors: 张健
Original assignee: Shandong New Time Pharmaceutical Co Ltd
Current assignee: Shandong New Time Pharmaceutical Co Ltd
Priority date: 2002-12-31
Filing date: 2002-12-31
Publication date: 2005-03-02
Anticipated expiration: 2022-12-31
Also published as: CN1478508A

Abstract

The present invention discloses a Chinese medicinal composition for treating fatty liver, and a preparation method thereof. The composition is composed of herba artemisiae capillaris, semen cassiae, rhubarb, agaric, hawthorn, water plantain, snakegourd fruit, glossy privet fruit, yerbadetajo herb, barbary wolfberry fruit, atractylodes rhizome, white atractylodes rhizome, tangerine peel, common cephalanoplos herb, bupleurum root and liquoric root. When the Chinese medicinal composition is prepared, the method of distillation, decoction and ethanol extraction is adopted to different components so as to achieve the purpose that efficient medicine is fully exerted. The composition has nice effect on treating fatty liver.

Description

A kind of Chinese medicine composition for the treatment of fatty liver and preparation method thereof

Invention field

The present invention relates to a kind of Chinese medicine composition, particularly be used for the treatment of the Chinese medicine composition of fatty liver, relate to the preparation method of said composition simultaneously.

Background technology

Fatty liver is meant the interior athero of hepatocyte that a variety of causes causes, is a common clinical picture.The fat content of normal liver accounts for the 3-5% of liver weight in wet base, and when athero, the fat content of liver can be up to the heavy 40-50% of liver.Under the different causes of disease, the fat that is deposited in the liver can be triglyceride, phospholipid, glycolipid, cholesterol ester etc.But most fatty livers are because due to the accumulation of triglyceride.

In recent years, along with the raising of people's living standard and drink, the increase of high fat diet, the sickness rate of fatty liver rises year by year, has become one of internal medicine common clinical.Especially young and middle-aged patient is more and more, has a strong impact on healthyly, influences work and quality of life.Therefore, to lipotropic clinical also increasing with experimentation.The prevention of fatty liver has become the clinical and more and more important problem of basic research of Chinese and western medicine with treatment.

Both at home and abroad the current research data to fatty liver shows that modern medicine mainly is conceived to the research of lipid metabolism at present, has obtained certain progress at aspects such as the diagnostic method of fatty liver, pathological studies.In treatment, medicine commonly used at present all is the systemic treatment medicine, and fatty liver is not had specific aim.Therefore, Chinese medicine or therapy of combining Chinese and Western medicine fatty liver receive increasing concern.Medicine and method in conjunction with whole body high fat of blood treatment fatty liver are increasing.But, not only can blood fat reducing but also can improve the disturbance state of whole body lipid metabolism, and can directly prevent because of liver fat is piled up the hepatic fibrosis that causes, the medicine of hardening necrosis does not have successfully precedent as yet.Therefore, the research blood fat reducing combines with protecting the liver, and can blood fat reducing again blood fat being piled up the hepatic injury that causes have and regulate and the new drug of restitution, is present important topic.

Medicine of the present invention is guidance with the theory of Chinese medical science, for the understanding of fatty liver and the latest developments of Chinese medicine fatty liver,, screen active drug in conjunction with modern medicine by clinical observation, according to clearing away heat-damp and promoting diuresis, the basic principles of formulating prescriptions of turbid antidotal of dispelling, the new side of the treatment fatty liver that develops.

Summary of the invention

One object of the present invention is to disclose a kind of Chinese medicine composition of new treatment fatty liver; Another object of the present invention is the method for a kind of new treatment fatty liver Chinese medicine composition of open preparation.

The crude drug of pharmaceutical composition of the present invention is formed and proportioning following (by weight):

Herba Artemisiae Scopariae 240-300 weight portion Semen Cassiae 240-300 weight portion Radix Et Rhizoma Rhei 130-190 weight portion

Polyporus 240-300 weight portion Fructus Crataegi 240-300 weight portion Rhizoma Alismatis 240-300 weight portion

The crude drug of pharmaceutical composition of the present invention is formed and proportioning also can be:

Fructus Trichosanthis 240-300 weight portion Fructus Ligustri Lucidi 240-300 weight portion Herba Ecliptae 240-300 weight portion

Fructus Lycii 240-300 weight portion Rhizoma Atractylodis 190-240 weight portion Rhizoma Atractylodis Macrocephalae 190-240 weight portion

Pericarpium Citri Reticulatae 130-190 weight portion Herba Cirsii 130-190 weight portion Radix Bupleuri 130-190 weight portion

Radix Glycyrrhizae 40-60 weight portion

Wherein, Semen Cassiae is to fry, and Radix Et Rhizoma Rhei is with stewed with wine, and the Rhizoma Atractylodis Macrocephalae is with parched with bran, and Radix Bupleuri is with processed with vinegar, and Rhizoma Atractylodis are with parched with bran, and Fructus Ligustri Lucidi is good with the wine steaming.

Be monarch drug with Herba Artemisiae Scopariae, Semen Cassiae in the side, clearing away heat-damp and promoting diuresis, let out turbid detoxifcation.Wherein Herba Artemisiae Scopariae goes into the liver and gall warp, is the special medicine of heat-clearing and toxic substances removing dampness removing; Semen Cassiae is gone into Liver and kidney two warps, and liver heat removing and eyesight improving is arranged, the merit of diuretic relieving constipation.Two medicines are harmonious, and become removing liver heat and toxic substances, dampness removing to let out turbid merit altogether, are monarch drug in the side.Ministerial drug in Radix Et Rhizoma Rhei, Rhizoma Alismatis, Polyporus, the Fructus Crataegi side of being, activating blood circulation to dissipate blood stasis, the stagnant removing food stagnancy of row.Damp-heat accumulation, venation is become estranged, the congestion retardance, accumulating Liver Channel is the major reason that forms fatty liver.Letting out turbid power deficiency because of considering the silt of monarch drug dampness removing, is the Radix Et Rhizoma Rhei with bitter cold, the poison that purges heat, and removing mass stagnates, and blood stasis expelling blood is cleansed the intestines and stomach, for the damp and hot outlet of opening, damp and hot heresy is gone from stool.Rhizoma Alismatis, Polyporus phase 5 in the side, promoting diuresis to eliminate damp pathogen is purged heat.Wherein Rhizoma Alismatis is sweet cold, goes into the kidney urinary bladder channel, and it is its special merit that promoting diuresis to eliminate damp pathogen is purged heat.Polyporus is sweet light flat, goes into spleen kidney urinary bladder channel, also for the diuresis eliminating dampness by diuresis will product, and diuretic and non-impairment of YIN.The two share, and can impel damp and hotly to go with urine.With Radix Et Rhizoma Rhei mutually 5, damp and hot front and back branch is disappeared.Fructus Crataegi is good at dissipating fluid-retention food, strengthening the spleen and stomach, row stagnation of QI, congestion disappears.We use it, activating blood circulation to dissipate blood stasis, and the stagnant removing food stagnancy of row is harmonious with Radix Et Rhizoma Rhei, and the capable power that stagnates of resolving blood stasis and dredging collateral more wins.

Adjuvant drug: Rhizoma Atractylodis, the Rhizoma Atractylodis Macrocephalae, Pericarpium Citri Reticulatae, Radix Bupleuri, Fructus Trichosanthis, Fructus Lycii, Fructus Ligustri Lucidi, Fructus seu radix camptothecae acuminatae (Fructus Camptothecae Acuminatae), Herba Cirsii.Because of Rhizoma Alismatis, Polyporus in the side are oozed the wet merit of the diuretic wet power deficiency of spleen invigorating fortune of having a surplus, so it is turbid to help it to add Rhizoma Atractylodis, Rhizoma Atractylodis Macrocephalae spleen reinforcing stomach reinforcing, damp eliminatingization.Multiple regulating the flow of vital energy with Pericarpium Citri Reticulatae transferred, and dampness is amusing.All medicines share, and help all medicine clearing away heat-damp and promoting diuresis of the monarch and his subjects to let out the merit of turbid detoxifcation with assistant; Radix Bupleuri reaches irritability to dredge first, transfers the usefulness of liver, second draws the through sick institute of full presciption medicine power; Fructus Trichosanthis sweetness and bitterness is cold, goes into lung stomach large intestine channel, the clearing away phlegm eliminating stagnation, and laxation is capable to stagnate, and more has the merit of the slow liver of soothing liver-QI concurrently; Fructus Lycii is sweet flat, enriching kidney essence, nourishing the liver to improve visual acuity.Fructus Ligustri Lucidi is bitter sweet flat, and merit is apt to invigorating the liver and kidney, strong waist knee joint.The sweet acid of Herba Ecliptae is cool, also is the product of removing heat from blood the kidney invigorating tonifying YIN.The three is harmonious, the nourishing kidney easing the affected liver, and clearing away heat-fire, the liver heat removing of tonifying liver body is used; The sweet cold of Herba Cirsii for the dispel product of silt, detoxification and promoting urination of removing heat from blood, can be helped the power that helps the monarch and his subjects' clearing away heat-damp and promoting diuresis to eliminate the phlegm.

Messenger drug: messenger drug in Radix Glycyrrhizae coordinating the actions of various ingredients in a prescription and the middle emergency side of being.In addition, Radix Bupleuri can draw all medicines and go into Liver Channel, also has the merit of guiding action concurrently.

In sum, it is various that prescription of the present invention is formed monarch, though flavour of a drug are how and not heterogeneous, compatibility is rigorous and orderly, all medicines complement each other, and Liver and kidney is also controlled, the specimen people having the same aspiration and interest, clearing away heat-damp and promoting diuresis and non-impairment of YIN, activating blood circulation to dissipate blood stasis and non-blood trouble become clearing away heat-damp and promoting diuresis, detoxifying and descending turbid, the merit of the silt easing the affected liver of dispelling altogether.Mainly treating fatty liver card belong to damp and hot in resistance, disease is seen body obesity, chest distress, abdominal distention, liver pain, fatigue and weakness, the whole body is stranded heavy, doublely sees vomiting and nausea, feeling thirst but no desire to drink, the urine yellow skin, it is not well to defecate, red tongue with yellow fur is thick, card persons such as slippery and rapid pulse.Or the history of being addicted to drink, hepatitis history, blood fat does not obviously increase the person.

This preparation of drug combination method:

More than ten Six-elements, get Radix Bupleuri, Rhizoma Atractylodis, the Rhizoma Atractylodis Macrocephalae, Pericarpium Citri Reticulatae and pulverize, add Herba Artemisiae Scopariae and decoct and extract volatile oil, volatile oil decocts with water 0.4-1 hour with beta-schardinger dextrin-system clathrate, medicinal residues, filters, filtrate merges with the distillation rear solution; Other gets Rhizoma Alismatis, Fructus Ligustri Lucidi, Radix Et Rhizoma Rhei, Semen Cassiae pulverizing, extracts three times with alcohol heating reflux, and each 1-2 hour, merge extractive liquid, filtered, device collection in addition behind the filtrate recycling ethanol; Get all the other medicines such as Fructus Trichosanthis again and decoct with water twice, each 0.5-1.5 hour, collecting decoction filtered, and filtrate merges with said extracted liquid, concentrates the adding dextrin, stirs evenly spray drying; Get dry powder, add volatile oil beta cyclodextrin inclusion complex, protein sugar 10 weight portions are behind the mix homogeneously, at last directly or add pharmaceutically acceptable excipient and make clinical acceptable forms, as tablet, pill, masticatory, oral liquid, capsule, granule etc. through conventional operation.

This compositions has significant effect in the treatment fatty liver, medicine and high fat diet added blood fat due to the ethanol raises, the increase of intrahepatic fat content has significant reduction effect, medicine and high fat diet are added pathology of livers has significant improvement effect due to the ethanol.

This composite preparation (the flat granule of fat liver) to ethionine and high fat diet add serum TC H, TC that ethanol causes, LDL raises that significant reduction effect is arranged, the HDL that reduces then there is remarkable rising effect, the action intensity and the lovastatin of high dose are suitable, can make TCH, LDL return to normal level.TG, the rising of Gn content in the liver are had significant reduction effect, and the action intensity and the lovastatin of high dose are suitable, can make liver interior TC, Cn return to normal level.Rat liver steatosis, special mess harm, cell infiltration all there is significant improvement effect.The flat granule of fat liver is to ip CCl ₁After the mice serum AST, ALT content that cause raise remarkable reduction effect arranged, action intensity and bifendate high, middle dosage are suitable.Following experimental example is used to further specify the present invention.Following material all is suitable for each experimental example.

Material:

Be subjected to the reagent thing: the flat granule medicinal liquid of fat liver: be equivalent to contain crude drug amount 4.5g/ml, Zhong Hui pharmaceutcal corporation, Ltd provides by Yangzhou, Jiangsu, lot number: 980620.People's consumption per day is the 85.5g crude drug.The time spent water is made into the suspension of desired concn.

Lovastatin: North China Pharmaceutical Co produces, lot number 971102.People's consumption per day is 40mg.

LIANBENSHUANGZHI DIWAN: the Beijing XieHe medicine Factory produces, lot number: 980406.People's consumption per day is 75-150mg.

Dosage is provided with: 70kg day for human beings dose is 85.5g.Through conversion, rat height, little, low dosage be youngster 30.8g.kg, 15.4g/kg, 7.7g/kg respectively, is equivalent to 25.2,12.6,6.3 times of 70kg day for human beings dosing, presses the volume gastric infusion of 1ml/100g body weight.The high, medium and low dosage of mice is respectively 44.5g/kg, 22.2g/kg, 11.1g/kg, is equivalent to 36.4,18.2,9.1 times of 70kg day for human beings dosing, presses the volume gastric infusion of 0.2ml/10g body weight.Water matched group and positive control drug.All by with the upper volume gastric infusion.Lovastatin rat dosage 7.2mg/kg is equivalent to 12.6 times of 70kg day for human beings dosing, and bifendate mice dosage 11.7mg/kg is equivalent to 12.6 times of day dosing.Bifendate mice dosage 11.7mg/kg is equivalent to 18.2 times of 70kg day for human beings dosing.

Animal subject: Kunming kind white mice, available from Shandong Medical University's Experimental Animal Center, the quality certification number: Shandong kinoplaszm 970102.Wistar kind rat, available from Shandong Province's Experimental Animal Center, the quality certification number: No. 970101, Shandong kinoplaszm.

Test apparatus: ultraviolet spectrophotometer UV-2100, refrigerated centrifuge, Potter-Elvehjem Tissue Grinders etc.

1. composite preparations of experimental example (the flat granule of fat liver) influence 60 of Wistar people Mus to what ethionine caused fatty liver, male, be divided into six groups at random by body weight: normal control group, second sulfur helium acid profile matched group, lovastatin matched group, flat high, little, the low dose group of fat liver.Gastric infusion 1ml/100g, continuous 10 people.The 8th day of administration, except that the normal control group, the surplus ig ethionine 250mg/kg that respectively organizes of its tool ¹Fasting was 12 hours in the 10th day, and the socket of the eye vein is got blood, and the centrifugal 15min of 2500rpm gets serum, measured CHO, TG, tlDL, LDL, and the result organizes a t check, sees Table 1: dissect rat immediately after getting blood, get part liver homogenate and measure glycogen Gn in the hepatic tissue ^2,3With TC content ¹The result organizes a t check, see Table 2: other gets the part liver, do histopathology procuratorial work with 10% formalin fixed: specimen stripping and slicing → fixation of tissue → fixedly post processing → block staining → paraffin method → dehydration, transparent step by step, each 30 minute hands → secondary waxdip, 90 minutes for the first time, 30 minutes → embedding → section → bonding die → dewaxing → ethanol aquation → washings at different levels for the second time → conventional H E dyeing → dehydration step by step, each 20 minutes → transparent secondary → resin encapsulation → light microscopic is checked down.Evaluation criterion is as follows, and the result carries out Ridit and analyzes, and sees Table 3.

The flat granule of table 1 fat liver to the influence of rat body weight (g) (x ± s, n=20)

Group dosage TCH (mmol/L) TG (mmol/L) HDL (mmol/L) LDL (mmol/L)

(g/kg)

Normal control group---2.573 ± 0.321 0.766 ± 0.310 0.536 ± 0.018 1.6810.183

Model control group---3.959 ± 0.914### 2.351 ± 0.833### 0.271 ± 0.066### 2.593 ± 0.9398#

Lovastatin 0.0072 2.553 ± 0.660*** 1.609 ± 0.233###* 0.358 ± 0.072###* 1.847 ± 0.708

High dose 30.8 2.626 ± 0.651** 1.708 ± 0.418###* 0.366 ± 0.070###** 1.915 ± 0.731

Middle dosage 15.4 3.016 ± 0.500* 1.676 ± 0.505###* 0.340 ± 0.078### 2.241 ± 0.536#

Low dosage 7.7 3.297 ± 0.230###* 2.051 ± 0.891### 0.390 ± 0.041### 2.286 ± 0.345##

Annotate: with the normal control group than #p＜0.01, ##p＜0.01, ###p＜0.001

With model control group than * p＜0.05, * p＜0.01, * * * p＜0.001

By table 1 result as seen, people Mus filling stomach is given; Liver gives TCH, TG behind the ethionine, LDL and all significantly raises, and HDL then significantly reduces.Give behind the flat granule of fat liver TCH, TC, the LDL of rising are significantly reduced, the HDL that reduces then significantly raises, its drug action intensity has certain dose-dependence, the action intensity of high dose (30.8g/kg) and lovastatin (0.0072g/kg) are suitable, can make TCH, LDL return to normal level.

The flat granule of table 2 fat liver to ethionine cause the influence that TG in the rats'liver, Gn change (x ± s, n=10)

Group dosage TG (mmol/100g) Gn (g/100g)

(g/kg)

The normal control group---0.900 ± 0.321 0.636 ± 0.120

Model control group---1.446 ± 0.223### 1.238 ± 0.313###

Lovastatin 0.0072 0.997 ± 0.348** 0.711 ± 0.127***

High dose 30.8 0.732 ± 0.330*** 0.681 ± 0.237***

Middle dosage 15.4 1.061 ± 0.405* 0.909 ± 0.209##*

Low dosage 7.2 1.251 ± 0.553 0.969 ± 0.240###*

Annotate: with the normal control group than ##p＜0.01, ###p＜0.001

With model control group than * p＜0.05, * * p＜0.01, * * * p＜0.001

By table 2 result as seen, rat oral gavage gives behind the ethionine that TG, Gn content all significantly raise in the liver.Give behind the flat granule of fat liver liver interior TG, Gn are significantly reduced, its drug action intensity has tangible dose-dependence, and the action intensity of high dose (30.8g/kg) and lovastatin (0.0072g/kg) are suitable, can make liver interior TG, Gn return to normal level.

Pathology procuratorial work report:, do not see that greasy feeling or other are unusual except that model control group hepatic tissue slightly the swelling.The surplus liver outward appearance of respectively organizing there is no unusually.Microscopy is respectively organized lesion degree and is scored by following grade:

A. no obvious corresponding change in the section is "-".

B. accidental corresponding pathological change in the sheet, pathological changes are dispersed in and distribute or single generation, and extent of disease accounts for below 1/4 of the full visual field, is "+".

C. corresponding pathological change is obvious, and in the form of sheets or the distribution of trooping, the 1/4-1/2 that extent of disease accounts for the full visual field counts " ++ ".

D. corresponding lesion degree is serious, and pathological changes is big lamellar and distributes, and occupies full lobule or reaches more than 1/2 of the full visual field, count " +++".

The flat granule of table 3 fat liver causes the influence of pathology of livers to ethionine

Group dosage n The dead cell infiltration of steatosis special mess ring

(g/kg)

- + ++ +++ - + ++ +++ - + ++ +++

The normal control group---10 10 10091002710

Model control group---10 10 54 0### 172 0### 0820

Low dosage 7.2 10 10 10 0*** 770 0** 2710

Middle dosage 15.4 10 10 30 0** 770 0** 370 0*

High dose 30.8 10 10 20 0** 990 0*** 160 0*

Lovastatin 0.0072 10 10 20 0** 880 0** 280 0*

Annotate: with the normal control group than p＜0.001

With model control group than * p＜0.05, * * p＜0.01, * * * p＜0.001

By table 3 data as seen, the flat granule of fat liver causes rat liver steatosis, little focal necrosis, cell infiltration to ethionine all significant improvement effect.

2. composite preparations of experimental example (the flat granule of fat liver) are to the influence of alcoholic fatty liver

70 of Wistar male rats, body weight 150-180g gets 10 and normally raises as the normal control group, and all the other animals give the mixed fodder that 79.5% Semen Maydis powder, 20% Adeps Sus domestica, 0.5% cholesterol are made, and other 30% ethanol is cooked beverage ⁵Raise after 1 month, CHO, TG, HDL, LDL are measured in the blood sampling of part animal, live and do histopathologic examination extremely, determine to have formed the fatty liver model.All the other animals now are divided into 5 groups at random: the flat high, medium and low dosage group of model control group, bifendate matched group, fat liver, ig administration except that the normal control group, 1ml/100g, everyone once, continuous 30 days, normal control group ig equivalent NS.Fasting is 12 hours behind the last medicine, and the socket of the eye vein is got blood, the centrifugal 15min of 2500rpm, get serum, measure CHO, TG, HDL, LDL, the result carries out: t check between group sees Table 4: get and dissect rat behind the blood immediately and get part liver homogenate and measure glycogen 23 and TG in the hepatic tissue, the result organizes a t check, see Table 5: other gets the part liver, does histopathology procuratorial work (method is the same) with 10% formalin fixed, and evaluation criterion is as follows, the result carries out Ridit and analyzes, and sees Table 6.

The influence that the flat granule of table 4 fat liver changes the alcoholic fatty liver rat fat (x ± s, n=10)

Group dosage TCH (mmol/L) TG (mmol/L) HDL (mmol/L) LDL (mmol/L)

(g/kg)

Normal control group---2.460+0.530 0.766 ± 0.310 0.659 ± 0.172 1.557 ± 0.600

Model control group---3.372 ± 1.079# 2.447 ± 0.813### 0.233 ± 0.061### 1.689 ± 1.247

Lovastatin 0.0072 2.553 ± 0.660 1.636 ± 0.532###*, 0.306 ± 0.060###* 1.613 ± 0.687

High dose 30.8 2.160 ± 0.447** 1.640 ± 0.319###* 0.366 ± 0.070###*** 1.193 ± 0.607

Middle dosage 15.4 2.574 ± 0.731 1.655 ± 0.451###* 0.290 ± 0.081 1.503 ± 0.825

Low dosage 7.7 2.626 ± 0.617 1.842 ± 0.638 0.279 ± 0.052 1.364 ± 0.669

Annotate: with the normal control group than #P＜0.05, ###p＜0.001

With model control group than * p＜0.05, * * p＜0.05, * * p＜0.01

By table 4 result as seen, alcoholic fatty liver rat serum TCH, TG all significantly raise, and HDL then significantly reduces, and LDL does not have significant change.Give can make TCH, the TG of rising, significantly reduction behind the flat granule of fat liver, the HDL that reduces then significantly raises, and LDL is not made significant difference.

The influence that the flat granule of table 5 fat liver changes TG, Gn in the alcoholic fatty liver rats'liver (x ± s, n=10)

Group dosage TG (mmol/100g) Gn (mmol/100g)

(g/kg)

The normal control group---0.689 ± 0.241 0.715 ± 0.350

Model control group---2.201 ± 0.700### 1.259 ± 0.473##

Lovastatin 0.0072 0.781 ± 0.454*** 0.820 ± 0.416*

High dose 30.8 0.982 ± 0.289#*** 0.723 ± 0.330**

Middle dosage 15.4 0.985 ± 0.283#*** 0.997 ± 0.348

Low dosage 7.7 1.053 ± 0.389#*** 1.251 ± 0.553#

Annotate: with the normal control group than #p＜0.05, ##p＜0.01, ###p＜0.001

With model control group than * p＜0.05, * * p＜0.01, * * * p＜0.001

By table 5 result as seen, TG, Gn content all significantly raise in the ethanol fat hepatomegaly Hepar Mus.Giving can to make behind the flat granule of fat liver in the liver of rising TG, Gn significantly to reduce its drug action intensity has tangible dose-dependence, and the action intensity of high dose (30.8g/kg) and lovastatin (0.0072g/kg) are quite.

The pathologic finding report: model group internal organs peplos is slightly nervous, and the section light yellow complexion has slight greasy feeling, and all the other respectively organize the equal Non Apparent Abnormality of appearance.Microsection manufacture is the same.Microscopy: the model group liver has steatosis in various degree, and the endochylema sky is bright, and loosing in the endochylema has circular fat not of uniform size to drip, and the severe patient fat drop is full of whole endochylema, karyon is pressed on one side, and serve as obviously with nearly peplos place, distribute along the lobule central area.Subregion periodical observability necrosis and cell infiltration.The fibrosis hypertrophy is seen at the end.It is all not obvious that all the other respectively organize pathological changes.Grade scoring is as follows:

1. no obvious corresponding pathological change in the section is "-".

2. accidental corresponding pathological change in the sheet, pathological changes are dispersed in and distribute or single generation, and extent of disease accounts for more than 1/4 of the full visual field, is "+".

3. corresponding pathological change is obvious, and in the form of sheets or the distribution of trooping, the 1/4-1/2 that extent of disease accounts for the full visual field counts " ++ ".

4. corresponding lesion degree comes heavy, and pathological changes is big lamellar and distributes, and occupies full lobule or reaches more than 1/2 of the full visual field, count " +++".

The flat granule of table 6 fat liver is to the influence of alcoholic fatty liver rat liver pathological change

Group dosage n The dead cell infiltration of steatosis special mess ring

(g/kg) - + ++ +++ - + ++ +++ - + ++ +++

The normal control group---10 910082002710

Model control group---10 024 4### 064 0### 0820

Low dosage 7.2 10 910 0*** 820 0*** 280 0*

Middle dosage 15.4 10 820 0*** 730 0*** 370 0*

High dose 30.8 10 10 00 0*** 820 0*** 460 0*

Lovastatin 0.0072 10 910 0*** 910 0*** 280 0*

Annotate: with the normal control group than ###p＜0.001

With model control group than * p＜0.05, * * p＜0.01, * * * p＜0.001

By table 6 data as seen, the flat granule of fat liver all has significant improvement effect to the degeneration of alcoholic fatty liver rat liver fat, little focal necrosis, cell infiltration.

3. composite preparations of experimental example (the flat granule of fat liver) are to CCl ₄Due to the influence of hepatic injury

72 of 18-20g Kunming mouses, male and female half and half are divided into six groups at random by body weight: normal control group, model control group, bifendate matched group, the flat high, medium and low dosage group of fat liver.Irritate stomach and give about 0.2ml/10g, continuous 7 people.2h behind the last medicine, ip0.25%CCl except that the normal control group ₁One olive oil 10ml/kg ^[6]The socket of the eye vein is got blood behind the 24h, and the centrifugal 15min of 2500rpm gets serum, measure AST, ALT, the result organizes a t check, sees Table 7: dissect mice immediately after getting blood, get the part liver, do histopathology procuratorial work (method is the same) with 10% formalin fixed, evaluation criterion is as follows, and the result carries out Ridit and analyzes, and sees Table 8.

The flat granule of table 7 fat liver is to CCL ₁Due to hepatic injury mice serum AST, ALT influence (x ± s, n=12)

Group dosage (g/kg) AST (U) ALT (U)

Normal control group---47.2 ± 13.5 51.1 ± 15.5###

Model control group---129.3 ± 26.5### 206.5 ± 15.4###***

Bifendate group 0.0117 89.5 ± 24.3###** 127.5 ± 26.7###***

Low dosage 44.5 86.8 ± 24.0###** 125.6 ± 19.8###***

Middle dosage 22.2 92.6 ± 17.5###** 129.8 ± 19.2###***

High dose 11.2 99.1 ± 30.6###* 140.3 ± 20.3###***

Annotate: with the normal control group than #p＜0.05, ###p＜0.001

With model control group than * p＜0.05, * * p＜0.01, * * * p＜0.001

By table 7 result as seen, ip in mice gives CCL ₁Back serum AST, ALT content all significantly raise.Give behind the flat granule of fat liver serum AST, the ALT of rising are significantly reduced, but can not make serum AST, ALT recover normal level, its drug action intensity has certain dose-dependence, and wherein the action intensity of high dose (44.5g/kg), middle dosage (22.2g/kg) and bifendate (0.0117g/kg) are suitable.

Pathological examination results: 6 groups of specimen outward appearances there is no obvious enlargement, atrophy and obviously downright bad, and tangent plane does not have tangible greasy feeling.Microscopy: compare with the normal control group, the all visible significantly hepatic necrosis of model control group and each medication group, acidophilia's degeneration and cell infiltration mainly are positioned at around the central vein and the portal area, in spite of illness in a disguised form to lighter, each group there is no proliferation of fibrous tissue and steatosis in the middle of the lobule.Compare with the damage matched group, each medication group degeneration necrosis degree is lighter, but the performance of endochylema puffing, it is little that each organizes difference.Liver cytoplasm puffing, hepatocyte acidophilia are become, and the anti-damage performance of soaking the ravine of the sex expression of hepatic necrosis equivalent damage and inflammatory cell is by following standard scoring:

The glad performance of the various damages of hepatocyte:

(-) expression incognizable disease reason changes.

Corresponding pathological change takes place in the accidental several cells of (+) expression, and distribution is dispersed in.

Corresponding pathological change takes place in (++) expression 1/3 left and right sides cell, and is distributed more widely.

(+++) expression has about half approximately even corresponding pathological change takes place more cell.

Cell infiltration:

Inflammatory cell is can not see in (-) expression basically.

(+) expression inflammatory cell is accidental in most visuals field.

(++) is illustrated in and easily sees in most visuals field and be dispersed in distribution.

(+++) expression inflammatory cell sees more, and assembles in the part, replaces part and cellularity.

The flat granule of table 8 fat liver is to CCL ₁Cause the influence of pathology of livers

Dosage Hepatocyte puffing hepatocyte acidophilia becomes the hepatic necrosis cell infiltration

Group n

(g/kg)

--- + ++ +++ --- + ++ +++ --- + ++ +++ --- + ++ +++

The normal control group---12 3810810075004800

Model control group---12 2721024 6### 054 3### 3711

Low dosage 11.2 12 2811028 2### 146 1### 3621

Middle dosage 22.2 12 480038 1### 01 0### 4610

High dose 44.5 12 2820019 2### 183 0##* 3711

Bifendate group 0.0117 82600044 0###* 031 1### 3621

Annotate: with the normal control group than ##p＜0.01, ###p＜0.001

With model control group than * p＜0.05

By table 8 data as seen, mice gives CCL ₁Back pathology of livers becomes and hepatic necrosis based on the hepatocyte acidophilia, and only high dose group (44.5g/kg) is to the hepatic necrosis effect of being significantly improved after giving the flat granule of fat liver, and all the other all do not have obvious influence.

4. composite preparations of experimental example (the flat granule of fat liver) are to the influence of hyperlipidemia due to the high fat diet

60 of Wistar male rats, body weight 120-140g is divided into 6 groups: normally to matched group, model control group, lovastatin matched group, the flat high, medium and low dosage group of fat liver, each Mus ig fat milk except that the normal control group ^[7]Ml/100g (10% cholesterol, 20% Adeps Sus domestica, 2% sodium cholate, 1% methylthiouracil), once a day, continuous 7 people.Normal control group ig equivalent NS.Beginning administration in the 8th day, 1ml/100g, once a day, and continuous 10 days, normal control group ig equivalent NS.Fasting is 12 hours behind the last medicine.The socket of the eye vein is got blood, and the centrifugal 15min of 2500rpm gets serum, measures CHO, TG, HDL, LDL, and the result organizes a t check, sees Table 9.

The flat granule of table 9 fat liver to high fat diet cause the influence that rat fat changes (x ± s, n=10)

Group dosage TCH (mmol/L) TG (mmol/L) HDL (mmol/L) LDL (mmol/L)

(g/kg)

The normal control group---2.086 ± 0.265 0.732 ± 0.227 0.663 ± 0.175 1.177 ± 0.359

Model control group---4.038 ± 0.392### 1.765 ± 0.546### 0.427 ± 0.092## 2.416 ± 0.590###

Lovastatin 0.0072 2.126 ± 0.832*** 1.325 ± 0.541## 0.574 ± 0.133* 0.811 ± 0.840***

High dose 30.8 2.356 ± 0.486*** 1.382 ± 0.362### 0.591 ± 0.112** 1.036 ± 0.457***

Middle dosage 15.4 2.432 ± 0.360#*** 1.454 ± 0.446### 0.555 ± 0.119* 1.012 ± 0.365***

Low dosage 7.7 2.559 ± 0.439##*** 1.531 ± 0.117### 0.526 ± 0.081#* 1.010 ± 0.105***

With model control group than * * p＜0.05, * * p＜0.01, * * * p＜0.001

By the result as seen, rat oral gavage gives that TCH, TG, LDL all do not have remarkable rising in the high fat diet bleeding from anus, HDL then obviously work reduce.After giving the flat granule of fat liver the TCH of rising, LDL are significantly reduced, the HDL that reduces then significantly raises, and TG is also had certain reduction effect, but no difference of science of statistics.

More than each experimental example result show: TCH, the TG that the flat granule of (1) fat liver causes ethionine, LDL raise significant reduction effect, to the then significantly rising effect of HDL that reduces, its drug action intensity has certain agent reason dependence, his intensity is cut down in the action intensity of high dose (30.8g/kg) and Lip river certain problem dependence, the action intensity of high dose (30.8g/kg) and lovastatin (0.0072g/kg) are suitable, can make TCH, LDL return to normal level.TG, Gn content all significantly raise in the liver that ethionine is caused significant reduction effect, its drug effect has tangible dose-dependence with intensity, the action intensity of high dose (30.8g/kg) and Liprevil (0.0072g/kg) are suitable, can make liver interior TG, Gn return to normal level.Ethionine is caused rat liver steatosis, little focal necrosis, cell infiltration significant improvement effect is all arranged.(2) the flat granule of fat liver has remarkable reduction effect to the content that alcoholic fatty liver Serum TC H, TG raise, and its drug action intensity has tangible agent reason dependence, and the action intensity of high dose (30.8g/kg) and lovastatin (0.0072g/kg) are suitable.Alcoholic fatty liver rat liver steatosis, little focal necrosis, cell infiltration all there is significant improvement effect.(3) the flat granule of fat liver is to ip CCL ₁After the remarkable reduction effect that all raise of the mice serum AST, the ALT content that cause, but can not make serum AST, ALT return to normal level, its medicine action intensity has certain dose-dependence, and the action intensity of high dose (44.5g/kg), middle dosage (22.2g/kg) is more suitable than fat (0.0117g/kg) with biphenyl.To ip CCL ₁After the mouse liver pathological change that causes, only high dose group (44.5mg/kg) is to the hepatic necrosis effect of being significantly improved, all the other all do not have obvious influence.(4) TCH, LDL raise remarkable reduction effect are arranged in the flat granule of fat liver the blood that high fat diet is caused, and the HDL that reduces is then had remarkable rising effect, and TG is also had certain reduction effect, but no difference of science of statistics.

The following example all can be realized the effect of above-mentioned experimental example.

Embodiment 1:

Herba Artemisiae Scopariae 270g Semen Cassiae 270g Radix Et Rhizoma Rhei 162g

Polyporus 270g Fructus Crataegi 270g Rhizoma Alismatis 270g

Wherein, Semen Cassiae is got and is fried, and Radix Et Rhizoma Rhei is got stewed with wine.

Herba Artemisiae Scopariae decoct to be extracted volatile oil, and volatile oil is with beta-schardinger dextrin-system clathrate; Get Rhizoma Alismatis, Radix Et Rhizoma Rhei, Semen Cassiae pulverizing, extract three times with alcohol heating reflux, each 1.5 hours, merge extractive liquid, filtered, device collection in addition behind the filtrate recycling ethanol; Get Polyporus again, Fructus Crataegi decocts with water twice, each 1 hour, collecting decoction filtered, and concentrated to add dextrin 250g, stirred evenly spray drying; Get dry powder, add volatile oil beta cyclodextrin inclusion complex, protein sugar 10g, behind the mix homogeneously, dry granulation is made granule 500g, promptly gets granule.Suitable crude drug 3 grams of every gram, every packed 8g, oral, a 8g, 3 times on the one, or follow the doctor's advice.

Embodiment 2:

Herba Artemisiae Scopariae 270g Semen Cassiae 270g Radix Et Rhizoma Rhei 162g

Polyporus 270g Fructus Crataegi 270g Rhizoma Alismatis 270g

Fructus Trichosanthis 270g Fructus Ligustri Lucidi 270g Herba Ecliptae 270g

Fructus Lycii 270g Rhizoma Atractylodis 216g Rhizoma Atractylodis Macrocephalae 216g

Pericarpium Citri Reticulatae 162g Herba Cirsii 162g Radix Bupleuri 162g

Wherein, Semen Cassiae is got and is fried, and Radix Et Rhizoma Rhei is got stewed with wine, and the Rhizoma Atractylodis Macrocephalae is got parched with bran, and Radix Bupleuri is got processed with vinegar, and Rhizoma Atractylodis are got parched with bran, and Fructus Ligustri Lucidi is got wine and steamed.

More than ten five tastes, get Radix Bupleuri, Rhizoma Atractylodis, the Rhizoma Atractylodis Macrocephalae, Pericarpium Citri Reticulatae and pulverize, add Herba Artemisiae Scopariae and decoct and extract volatile oil, volatile oil decocts with water 0.5 hour with beta-schardinger dextrin-system clathrate, medicinal residues, filters, filtrate merges with the distillation rear solution; Other gets Rhizoma Alismatis, Fructus Ligustri Lucidi, Radix Et Rhizoma Rhei, Semen Cassiae pulverizing, extracts three times with alcohol heating reflux, and each 1.5 hours, merge extractive liquid, filtered, device collection in addition behind the filtrate recycling ethanol; Get all the other medicines such as Fructus Trichosanthis again and decoct with water twice, each 1 hour, collecting decoction filtered, and filtrate merges with said extracted liquid, concentrated adding dextrin 250g, stirred evenly spray drying; Get dry powder, add volatile oil beta cyclodextrin inclusion complex, protein sugar 10g, behind the mix homogeneously, dry granulation is made granule 1000g, promptly gets granule.Suitable crude drug 3 grams of every gram, every packed 8g, oral, a 8g, 3 times on the one, or follow the doctor's advice.

Embodiment 3:

Herba Artemisiae Scopariae 270g Semen Cassiae 270g Radix Et Rhizoma Rhei 162g

Polyporus 270g Fructus Crataegi 270g Rhizoma Alismatis 270g

Fructus Trichosanthis 270g Fructus Ligustri Lucidi 270g Herba Ecliptae 270g

Pericarpium Citri Reticulatae 162g Herba Cirsii 162g Radix Bupleuri 162g Radix Glycyrrhizae 54g

More than ten Six-elements, get Radix Bupleuri, Rhizoma Atractylodis, the Rhizoma Atractylodis Macrocephalae, Pericarpium Citri Reticulatae and pulverize, add Herba Artemisiae Scopariae and decoct and extract volatile oil, volatile oil decocts with water 0.5 hour with beta-schardinger dextrin-system clathrate, medicinal residues, filters, filtrate merges with the distillation rear solution; Other gets Rhizoma Alismatis, Fructus Ligustri Lucidi, Radix Et Rhizoma Rhei, Semen Cassiae pulverizing, extracts three times with alcohol heating reflux, and each 1.5 hours, merge extractive liquid, filtered, device collection in addition behind the filtrate recycling ethanol; Get all the other medicines such as Fructus Trichosanthis again and decoct with water twice, each 1 hour, collecting decoction filtered, and filtrate merges with said extracted liquid, concentrated adding dextrin 250g, stirred evenly spray drying; Get dry powder, add volatile oil beta cyclodextrin inclusion complex, protein sugar 10g, behind the mix homogeneously, dry granulation is made granule 1000g, promptly gets granule.Suitable crude drug 3.56 grams of every gram, every packed 8g, oral, a 8g, 3 times on the one, or follow the doctor's advice.

Embodiment 4:

Herba Artemisiae Scopariae 260g Semen Cassiae 260g Radix Et Rhizoma Rhei 172g

Polyporus 260g Fructus Crataegi 260g Rhizoma Alismatis 280g

Fructus Trichosanthis 280g Fructus Ligustri Lucidi 280g Herba Ecliptae 280g

Fructus Lycii 250g Rhizoma Atractylodis 226g Rhizoma Atractylodis Macrocephalae 206g

Pericarpium Citri Reticulatae 172g Herba Cirsii 170g Radix Bupleuri 150g Radix Glycyrrhizae 58g

More than ten Six-elements, get Radix Bupleuri, Rhizoma Atractylodis, the Rhizoma Atractylodis Macrocephalae, Pericarpium Citri Reticulatae and pulverize, add Herba Artemisiae Scopariae and decoct and extract volatile oil, volatile oil decocts with water 0.5 hour with beta-schardinger dextrin-system clathrate, medicinal residues, filters, filtrate merges with the distillation rear solution; Other gets Rhizoma Alismatis, Fructus Ligustri Lucidi, Radix Et Rhizoma Rhei, Semen Cassiae pulverizing, extracts three times with alcohol heating reflux, and each 1.5 hours, merge extractive liquid, filtered, device collection in addition behind the filtrate recycling ethanol; Get all the other medicines such as Fructus Trichosanthis again and decoct with water twice, each 1 hour, collecting decoction filtered, and filtrate merges with said extracted liquid, concentrated adding dextrin 250g, stirred evenly spray drying; Get dry powder, add volatile oil beta cyclodextrin inclusion complex, protein sugar 10g, behind the mix homogeneously, dry granulation is made 500 of soft capsules, suitable crude drug 3.56 grams of every gram, every dress 4g, oral, one time two, 3 times on the one, or follow the doctor's advice.

Claims

1, a kind of Chinese medicine compositions for the treatment of fatty liver is characterized in that this pharmaceutical composition made by following raw material medicaments:

Herba Artemisiae Scopariae 240-300 weight portion Semen Cassiae 240-300 weight portion

Radix Et Rhizoma Rhei 130-190 weight portion Polyporus 240-300 weight portion

Fructus Crataegi 240-300 weight portion Rhizoma Alismatis 240-300 weight portion.

2, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw material medicaments:

Herba Artemisiae Scopariae 270 weight portion Semen Cassiaes 270 weight portions

Radix Et Rhizoma Rhei 162 weight portion Polyporus 270 weight portions

Fructus Crataegi 270 weight portion Rhizoma Alismatis 270 weight portions.

3, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw material medicaments:

Radix Et Rhizoma Rhei 130-190 weight portion Polyporus 240-300 weight portion

Fructus Crataegi 240-300 weight portion Rhizoma Alismatis 240-300 weight portion

Fructus Trichosanthis 240-300 weight portion Fructus Ligustri Lucidi 240-300 weight portion

Herba Ecliptae 240-300 weight portion Fructus Lycii 240-300 weight portion

Rhizoma Atractylodis 190-240 weight portion Rhizoma Atractylodis Macrocephalae 190-240 weight portion

Pericarpium Citri Reticulatae 130-190 weight portion Herba Cirsii 130-190 weight portion

Radix Bupleuri 130-190 weight portion.

4, pharmaceutical composition as claimed in claim 3 is characterized in that this pharmaceutical composition made by following raw material medicaments:

Radix Et Rhizoma Rhei 162 weight portion Polyporus 270 weight portions

Fructus Crataegi 270 weight portion Rhizoma Alismatis 270 weight portions

Fructus Trichosanthis 270 weight portion Fructus Ligustri Lucidi 270 weight portions

Herba Ecliptae 270 weight portion Fructus Lycii 270 weight portions

The Rhizoma Atractylodis 216 weight portion Rhizoma Atractylodis Macrocephalaes 216 weight portions

Pericarpium Citri Reticulatae 162 weight portion Herba Cirsiis 162 weight portions

Radix Bupleuri 162 weight portions.

5, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw material medicaments:

Radix Et Rhizoma Rhei 130-190 weight portion Polyporus 240-300 weight portion

Herba Ecliptae 240-300 weight portion Fructus Lycii 240-300 weight portion

Radix Bupleuri 130-190 weight portion Radix Glycyrrhizae 40-60 weight portion

6, pharmaceutical composition as claimed in claim 5 is characterized in that this pharmaceutical composition made by following raw material medicaments:

Radix Et Rhizoma Rhei 162 weight portion Polyporus 270 weight portions

Fructus Crataegi 270 weight portion Rhizoma Alismatis 270 weight portions

Herba Ecliptae 270 weight portion Fructus Lycii 270 weight portions

Radix Bupleuri 162 weight portion Radix Glycyrrhizaes 54 weight portions.

7, pharmaceutical composition as claimed in claim 5 is characterized in that this pharmaceutical composition made by following raw material medicaments:

Herba Artemisiae Scopariae 260 weight portion Semen Cassiaes 260 weight portions

Radix Et Rhizoma Rhei 172 weight portion Polyporus 260 weight portions

Fructus Crataegi 260 weight portion Rhizoma Alismatis 280 weight portions

Fructus Trichosanthis 280 weight portion Fructus Ligustri Lucidi 280 weight portions

Herba Ecliptae 280 weight portion Fructus Lycii 250 weight portions

The Rhizoma Atractylodis 226 weight portion Rhizoma Atractylodis Macrocephalaes 206 weight portions

Pericarpium Citri Reticulatae 172 weight portion Herba Cirsiis 170 weight portions

Radix Bupleuri 150 weight portion Radix Glycyrrhizaes 58 weight portions.

8, as claim 1,2,3,4,5,6 or 7 described pharmaceutical compositions, it is characterized in that Radix Et Rhizoma Rhei is the stewed with wine Radix Et Rhizoma Rhei in this pharmaceutical composition, Semen Cassiae is for frying Semen Cassiae.

9, as claim 3,4,5,6 or 7 described pharmaceutical compositions, it is characterized in that the Rhizoma Atractylodis Macrocephalae is a Rhizoma Atractylodis Macrocephalae (parched with bran) in this pharmaceutical composition, Radix Bupleuri is Radix Bupleuri (processed with vinegar), and Rhizoma Atractylodis are the parched with bran Rhizoma Atractylodis, and Fructus Ligustri Lucidi is a Fructus Ligustri Lucidi (steamed with wine).

10,, it is characterized in that this pharmaceutical composition adds excipient and makes clinical acceptable forms as claim 1,2,3,4,5,6 or 7 or described pharmaceutical composition.

11, as claim 3,4,5,6 or 7 described preparation of drug combination methods, it is characterized in that this method is: get Radix Bupleuri, Rhizoma Atractylodis, the Rhizoma Atractylodis Macrocephalae, Pericarpium Citri Reticulatae pulverizing, add Herba Artemisiae Scopariae and decoct extraction volatile oil, volatile oil is with beta-schardinger dextrin-system clathrate, medicinal residues decoct with water 0.4-1 hour, filter, filtrate merges with the distillation rear solution; Other gets Rhizoma Alismatis, Fructus Ligustri Lucidi, Radix Et Rhizoma Rhei, Semen Cassiae pulverizing, extracts three times with alcohol heating reflux, and each 1-2 hour, merge extractive liquid, filtered, device collection in addition behind the filtrate recycling ethanol; Get all the other medicines such as Fructus Trichosanthis again and decoct with water twice, each 0.5-1.5 hour, collecting decoction filtered, and filtrate merges with said extracted liquid, concentrates the adding dextrin, stirs evenly spray drying; Get dry powder, add volatile oil beta cyclodextrin inclusion complex, protein sugar 10 weight portions are behind the mix homogeneously, at last through conventional operation directly or add pharmaceutically acceptable excipient and make arbitrary dosage form in clinical acceptable tablet, oral liquid, capsule, the granule.

12, preparation of drug combination method as claimed in claim 11, it is characterized in that this method is: get Radix Bupleuri, Rhizoma Atractylodis, the Rhizoma Atractylodis Macrocephalae, Pericarpium Citri Reticulatae pulverizing, add Herba Artemisiae Scopariae and decoct extraction volatile oil, volatile oil is with beta-schardinger dextrin-system clathrate, medicinal residues decoct with water 0.5 hour, filter, filtrate merges with the distillation rear solution; Other gets Rhizoma Alismatis, Fructus Ligustri Lucidi, Radix Et Rhizoma Rhei, Semen Cassiae pulverizing, extracts three times with alcohol heating reflux, and each 1.5 hours, merge extractive liquid, filtered, device collection in addition behind the filtrate recycling ethanol; Get all the other medicines such as Fructus Trichosanthis again and decoct with water twice, each 1 hour, collecting decoction filtered, and filtrate merges with said extracted liquid, concentrated adding dextrin 250 weight portions, stirred evenly spray drying; Get dry powder, add volatile oil beta cyclodextrin inclusion complex, protein sugar 10 weight portions, behind the mix homogeneously, dry granulation gets granule.