CN1181875C

CN1181875C - Medicine for curing fat liver of obesity and its preparing method

Info

Publication number: CN1181875C
Application number: CNB021517851A
Authority: CN
Inventors: 张晴龙
Original assignee: Individual
Current assignee: Individual
Priority date: 2002-12-31
Filing date: 2002-12-31
Publication date: 2004-12-29
Anticipated expiration: 2022-12-31
Also published as: CN1425420A

Abstract

The present invention discloses medicine for treating obesity fatty liver, which is prepared from seven kinds of the traditional Chinese medicine, such as giant knotweed rhizome, processed pinellia tuber, water plantain, zedoary, peach kernels, fructus polygoni orientalis and liquorice, as raw materials. The present invention also discloses a method for preparing the medicine. The medicine of the present invention has the efficiency of removing dampness, reducing phlegm, activating blood circulation and eliminating abdominal mass. The present invention mainly treats the obesity fatty liver caused by body obesity, distention and stuffiness in chests and hypochondrium, nausea, vomit, dizziness, heavy limbs, abdominal distention, anorexia, unctuous furred tongues and thready and slippery pulse. According to the authentication of Chinese medicine, the present invention treats patients caused by wetness phlegm stasis. After being used in clinic, the present invention has the advantages of quick action, conspicuous effects and no adverse reaction.

Description

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

Affiliated technical field

The present invention relates to a kind of medicine for the treatment of obese fatty liver, being specifically related to a kind of is the Chinese patent medicine of feedstock production with the Chinese herbal medicine, the invention still further relates to the preparation method of this medicine.

Background technology

Fatty liver (fatty liver) is that multiple reason causes that the hepatocyte inner lipid accumulates too much a kind of pathological state.According to the cause of disease, after fatty liver is divided into obesity-related, ethanol, hepatitis, medicine and metabolic etc.And obese fatty liver accounts for more than 60% of whole fatty livers.It is low that fatty liver can cause liver function, becomes the factor that disease incidences such as hyperlipemia, coronary heart disease, hypertension, arteriosclerosis raise again.But with state of an illness delay fatty liver liver fibrosis due, liver cirrhosis, hepatic ascites, so that liver function is more low, has a strong impact on people's healthy and quality of life.

Incidence about primary disease, once report liver biopsy recall rate about 5% seventies, the end of the eighties, the Japan-US scholar of grade utilized the B ultrasonic generaI investigation to find, the pathogenesis of fatty liver rate accounts for 10% of average population, fat and diabetics 50% another show that from the report that a certain sub-district 2574 of Japanese OKiuawa occupies the real-time B ultrasonic mensuration of people The fatty liver prevalence rate total crowd's prevalence is 14%, less than 19 years old person only was 1.2%, along with the age increases, The fatty liver prevalence rate increases, summit progressively gradually descended again later at 40～49 years old.

China also has many pieces successively with the article of B ultrasonic as diagnostic means report The fatty liver prevalence rate, because sample object, age group are different with sex, the result is also inconsistent for report.For example Shanghai with the B ultrasonic generaI investigation, be 8.8% according to the report The fatty liver prevalence rate, and Shanghai City office worker's pathogenesis of fatty liver rate is 12.9% to a certain teacher in an institution of higher learning (1600 people); The Beijing area is 11% to 1051 workers' of 4 units B ultrasonic findings of the survey; 1119 government functionaries' in Nanjing, Jiangsu Province B ultrasonic findings of the survey are 10.2%, and the male is 11.4%, and the women is 6.8%;

Because living standard raising, dietary structure variation and prevention and health care measure relatively lag behind, the pathogenesis of fatty liver rate is still rising, and age of onset is more and more littler in recent years.Discovery Japanese children The fatty liver prevalence rate such as Tominaga are 2.6%, and the male is more than women (3.4% pair 1.8%), and year the lighter is only 6 years old.

Doctor trained in Western medicine is on the basis of emphasizing Diet Therapy and exercise therapy to the treatment of primary disease at present, adds and uses the medicine auxiliary treatment.These medicines comprise: (1) choline and L-carnitine: be only applicable to relevant dystrophic fatty liver.Choline participates in the methyl conversion, and carnitine promotes fatty acid oxidation and film healing; During the hepatocyte damaged, because synthetic deficiency of endogenous or body increase in demand may cause body L-carnitine malnutrition, the generation that suitably replenishes preventing fatty liver may be useful.(2) the unsaturated lecithin of multivalence: for the agent of hepatic sinusoidal endothelium regulating liver-QI cell membrane stability, can reduce lipid peroxidation, reduce liver cell fatty degeneration and inflammation of accompanying and fibrosis, but because of being rich in linoleic acid, to can not abstainer Ying Shenyong.(3) S-adenosylmethionine: influence its flowability and microviscosity by plasma membrane phospholipid and proteinic methylating; increase liver glutathion inside (GSH), sulfate radical and taurine level by changeing sulfation, effective to kwashiorkor, hepatotoxin and alcoholic fatty liver.(4) antioxidant: reduced form GSH, taurine, bata-carotene, vitamin E, Matodoxin, selenium organic compound (Ebselen), Silymarin and amino steroid derivative Lazaroid etc.; might reduce the hepatic fibrosis that oxidative stress infringement and lipid peroxidation are led to, but remain to be proved its definite curative effect.(5) ursodesoxycholic acid: the effect of similar cholesterol resin cholestyramine is arranged, but blood fat reducing, and can stablize liver plasma membrane and suppress mononuclear cell generation cytokine, there is report to claim the effect that NASH patient's tool is reduced ALT, AKP, GGT level and the fatty liver degree is alleviated.(6) lipid lowerers: many hypolipidemics that have objection may become to making blood fat more to concentrate on liver to carry out metabolism, impel lipid to store up on the contrary and damage liver function.Lipid lowerers such as the clofibrate of nicotinic acid class, Elastase and phenoxy acetic acid class, bezafibrate have potential liver toxicity, reduce untoward reaction such as carbohydrate tolerance and rising blood uric acid, even and the improvement of intrahepatic fat deposition nothing increases the weight of.Discover that recently HMGCoA reductase inhibitor simvastatin can suppress the propagation of liver Ito cell, and can significantly improve the liver function and the metabolism disorder of blood lipid of the Patients with Fatty Liver that continues to drink that whether its blood fat reducing curative effect and patient merge HCV is infected irrelevant.General Liprevil can significantly reduce the blood lipid level of high fat diet hyperlipemia and fatty liver rabbit, and the intrahepatic fat deposition also makes moderate progress.

Because fatty liver is because of various, the pathogenesis complexity, the lipoprotein metabolism disorder relates to multifactor too many levels, not only be reflected in the blood circulation level, also be reflected in tissue, cell and molecular level, after particularly noticing lipid peroxidation and inflammation and Fibrotic relation, people try hard to seek pharmaceutical intervention, regrettably still do not have satisfied medicine so far clinically.

Summary of the invention

The object of the present invention is to provide a kind of good effect, instant effect and do not have the medicine of the treatment obese fatty liver of obvious toxic-side effects.

Another object of the present invention is to provide the preparation method of this medicine.

A kind of medicine for the treatment of obese fatty liver provided by the invention is characterized in that it is the medicament of being made by the following weight proportion raw material:

Rhizoma Polygoni Cuspidati 2～6 Rhizoma Pinelliae Preparatum 1～5 Rhizoma Alismatis 1～5 Rhizoma Curcumae 1～5

Semen Persicae 1～3 Fructus Polygoni Orientalis 1～3 Radix Glycyrrhizae 0.5～1.5.

The above-mentioned medicine that is used for the treatment of obese fatty liver can be made said multiple dosage form on the pharmaceutics, as granule, capsule or tablet.

Above-mentioned materials of weight proportions is made the method for medicine of the present invention, may further comprise the steps:

(1) gets Rhizoma Polygoni Cuspidati, Rhizoma Pinelliae Preparatum, Rhizoma Alismatis, Semen Persicae, Fructus Polygoni Orientalis, Radix Glycyrrhizae Six-element, add 5～12 times of amount 50～85% ethanol, soaked 1～12 hour, heating and refluxing extraction 2～4 times, each 0.5～4 hour, merge alcohol extract, decompression recycling ethanol and to be concentrated into relative density be 1.02～1.08, leave standstill, filter, it is 1.201.25 that filtrate decompression is concentrated into relative density, vacuum drying, be ground into fine powder, get extract powders such as Rhizoma Polygoni Cuspidati;

(2) get Rhizoma Curcumae, add the water of 6～14 times of amounts, extracted volatile oil 4～16 hours, it is standby to collect volatile oil; The medicinal liquid behind the oil is carried in leaching, and is centrifugal, and being concentrated into relative density is 1.20-1.25, and vacuum drying is ground into fine powder, gets the Rhizoma Curcumae extract powder; Get 6～10 times of amounts of volatile oil beta-schardinger dextrin-, put in 20～40 ℃ of water and make saturated aqueous solution, volatile oil is dropped in the saturated aqueous solution of beta-schardinger dextrin-, stir, cold preservation is filtered, and drying promptly gets the volatile oil inclusion complex;

(3) get extract powder, Rhizoma Curcumae extract powder and volatile oil inclusion complex such as Rhizoma Polygoni Cuspidati, add soluble starch, mixing is granulated, and drying makes granule of the present invention.

Prescription of the present invention is reasonable, and rigorous and scientific is effective Chinese medicine preparation.We control belong to the damp-phlegm blood stasis blocking type for the obese fatty liver Chinese medical discrimination, invigorate blood circulation with the note of the ancient Chinese that disappears so control when dampness removing reduces phlegm, Rhizoma Polygoni Cuspidati bitter in the mouth cold in nature, the function clearing away heat-damp and promoting diuresis, in the blood circulation promoting recipe that reduces phlegm with being monarch drug.Rhizoma Alismatis is sweet, light, cold, returns kidney, urinary bladder channel, and light infiltration is wet, cold in nature expelling the heat-evil, and through bladder makes damp and hot heresy separate from urine with the promoting diuresis to eliminate damp pathogen heat clearing away." Compendium of Materia Medica rolls up 19 ": " the flat sweet in the mouth of Rhizoma Alismatis gas is and light, and light can oozing let out, so all thin diuretic of abnormal smells from the patient and diarrhea; taste have damp and hot; then nose heave and blurred vision tinnitus, and Rhizoma Alismatis is oozed its wet then heat also with going, and morale must make; clearing heat in QI system is up; weather is bright refreshing, so Rhizoma Alismatis has foster the five internal organs, and a physical strength profiting; control and revolve the merit of clever knowledge." Rhizoma Pinelliae Preparatum acrid in the mouth warm in nature, return spleen, stomach, lung meridian, the function drying dampness to eliminate phlegm, " book on Chinese herbal medicine meets the source ": " Rhizoma Pinelliae, Rhizoma Atractylodis, Poria are controlled damp-phlegm; Same Fructus Trichosanthis, Radix Scutellariae are controlled heat-phlegm; Same Rhizoma Arisaematis, Radix Peucedani is controlled wind-phlegm; Same Semen Sinapis, Folium Zingiberis are controlled cold-phlegm ... " the two share and gets final product the dampness removing heat clearing away, but drying dampness to eliminate phlegm is all ministerial drug altogether by the heresy of turbid damp again.Rhizoma Curcumae bitter in the mouth warm in nature is returned liver, spleen channel.Energy circulation of qi promoting removing blood stasis, the removing food stagnancy pain relieving.The flat bitter in the mouth of Semen Persicae, GUIXIN, liver, lung, large intestine channel.The function blood circulation promoting and blood stasis dispelling." medicine justice " " the Semen Persicae bitter in the mouth can be let out heat in blood, and body profit can be grown dryness of the intestine ... ", Fructus Polygoni Orientalis salty in the mouth cold in nature blood that can loose disappears.The three share the turbid power to disappear of common principal drug assistance blood circulation promoting and blood stasis dispelling, also is ministerial drug.The flat sweet in the mouth of Radix Glycyrrhizae property can be in harmonious proportion all medicinal for messenger drug, and all medicines share that prescription is proper, and the pathogenesis that hits can be played dampness removing altogether and reduce phlegm, the effect of note of the ancient Chinese of disappearing of invigorating blood circulation.

Medicine tool dampness removing of the present invention reduces phlegm, the effect of note of the ancient Chinese of disappearing of invigorating blood circulation.Cure mainly obese fatty liver, disease is seen: obesity, and breast side of body feeling of distension and oppression, the tending to vomit of feeling sick, dizzy nose heave, limbs are heavy, abdominal distension and anorexia, tongue fur is satiny, stringy and rolling pulse.Chinese medical discrimination belongs to damp-phlegm stasis of blood resistance person.After the clinic trial, effect is rapid, and effect is remarkable, has no adverse reaction.

The invention will be further described below by embodiment and toxicology and pharmacology experimental result.

Embodiment 1

Get Rhizoma Polygoni Cuspidati 1300g, Rhizoma Pinelliae Preparatum 800g, Rhizoma Alismatis 900g, Semen Persicae 500g, Fructus Polygoni Orientalis 800g, Radix Glycyrrhizae 200g, add 10 times of amount 75% ethanol, soaked 4 hours, heating and refluxing extraction 3 times, each 1.5 hours, merge alcohol extract, decompression recycling ethanol and be concentrated into to relative density be 1.02 (60 ℃), leave standstill, filter, it is 1.25 (60 ℃) that filtrate decompression is concentrated into relative density, vacuum drying, be ground into fine powder, get extract powders such as Rhizoma Polygoni Cuspidati.Other gets Rhizoma Curcumae 900g, adds 10 times of water gagings, extracts volatile oil 8 hours, and it is standby to collect volatile oil; The medicinal liquid behind the oil is carried in leaching, and is centrifugal, and being concentrated into relative density is 1.20 (60 ℃), and vacuum drying is ground into fine powder, gets the Rhizoma Curcumae extract powder.Get 8 times of amounts of volatile oil beta-schardinger dextrin-, put in 30 ℃ of water and make saturated aqueous solution, volatile oil is dropped in the saturated aqueous solution of beta-schardinger dextrin-, stirred 2 hours with 300 rev/mins of speed under 35 ℃ of temperature, cold preservation 40 hours is filtered, 40 ℃ of dryings promptly get the volatile oil inclusion complex.Get extract powder, Rhizoma Curcumae extract powder and volatile oil inclusion complexes such as Rhizoma Polygoni Cuspidati, add an amount of soluble starch, mixing is granulated, and drying is made 1000g, promptly gets granule of the present invention.

Embodiment 2

Get Rhizoma Polygoni Cuspidati 1500g, Rhizoma Pinelliae Preparatum 700g, Rhizoma Alismatis 1200g, Semen Persicae 300g, Fructus Polygoni Orientalis 700g, Radix Glycyrrhizae 200g, add 12 times of amount 65% ethanol, soaked 8 hours, heating and refluxing extraction 2 times, each 3 hours, merge alcohol extract, decompression recycling ethanol and be concentrated into to relative density be 1.08 (60 ℃), leave standstill, filter, it is 1.21 (60 ℃) that filtrate decompression is concentrated into relative density, vacuum drying, be ground into fine powder, get extract powders such as Rhizoma Polygoni Cuspidati.Other gets Rhizoma Curcumae 900g, adds 8 times of water gagings, extracts volatile oil 10 hours, and it is standby to collect volatile oil; The medicinal liquid behind the oil is carried in leaching, and is centrifugal, and being concentrated into relative density is 1.25 (60 ℃), and vacuum drying is ground into fine powder, gets the Rhizoma Curcumae extract powder.Get 10 times of amounts of volatile oil beta-schardinger dextrin-, put in 35 ℃ of water and make saturated aqueous solution, volatile oil is dropped in the saturated aqueous solution of beta-schardinger dextrin-, stirred 3 hours with 350 rev/mins of speed under 35 ℃ of temperature, cold preservation 30 hours is filtered, 35 ℃ of dryings promptly get the volatile oil inclusion complex.Get extract powder, Rhizoma Curcumae extract powder and volatile oil inclusion complexes such as Rhizoma Polygoni Cuspidati, add an amount of soluble starch, mixing is granulated, and drying is made 1000g, promptly gets granule of the present invention.

Toxicity and pharmacodynamics test

The present invention is to provide a kind of natural drug for the treatment of obese fatty liver, for proving its therapeutic effect and safety, the inventor uses the granule for preparing by the method that provides in the foregoing description to carry out toxicity and pharmacodynamics test, and result of study is as follows:

One, animal acute toxicity test

Acute toxicity test in mice studies show that granule of the present invention is irritated stomach (ig) administration, can't measure LD50.Use oral maximum dosage-feeding test instead.The result shows: press Cmax, maximum volume, a twice-daily at every turn and irritate stomach (ig) administration, the maximum dosage-feeding of mice administration is 376.0g crude drug/kg (is equivalent to intend clinical application 418 times), does not have tangible toxic reaction, observes no animal dead in the week.

Two, long-term toxicity test for animals

Granule 54,27 of the present invention and 9g/kg (in the crude drug amount, being equivalent to intend 60,30 and 10 times of clinical people's consumption) three dosage groups and blank groups are established in test, adopt the gastric infusion approach to give rat respectively, successive administration 6 months.Observe general situation features such as the appetite respectively organize rat, body weight, outward appearance sign,, carry out hematology, blood parameters inspection and pathological examination respectively in administration 3 months, 6 months and convalescent period.The result shows: granule of the present invention is to the not obviously influence of animal general signs, and administration is in the time of 3 months, and high dose groups of grains of the present invention significantly raise serum AST, ALP, the CREA of rat are with matched group relatively (P＜0.05); High dose also raise serum albumin and total protein, low dosage decreases to AST, ALT, ALP, BUN, CREA, but with blank group comparing difference not significantly (P＞0.05), the relatively more equal no significant difference (P＞0.05) of other hematologys and blood parameters inspection and blank group.Administration is in the time of 6 months, high dose groups of grains of the present invention significantly raise serum AST, ALT, ALP, BUN, the CREA (P＜0.05 or P＜0.01) of rat; Other hematologys and blood parameters inspection and blank group be no significant difference (P＞0.05) relatively all.After drug withdrawal 21 days the time, the discrepant biochemical indicator AST of granule administration group of the present invention, ALT, ALP, BUN, CREA have recovered normal, with blank group comparing difference not significantly (P＞0.05), other indexs and blank group comparing difference be remarkable (P＞0.05) not.Administration 3 months, 6 months removes high dose minority rats'liver to take a favourable turn-the moderate necrosis, the inflammation pathological change, zero difference between female, the tom.After the drug withdrawal 21 days, high dose group was respectively examined the internal organs pathology of livers and is alleviated, with blank group no significant difference relatively.Show to be the nontoxic amounts of reactants of rat less than 27.0g/kg.

Three, cure mainly relevant Pharmacodynamic test of active extract with function

Granule of the present invention is made up of Rhizoma Polygoni Cuspidati, Rhizoma Alismatis, Radix Glycyrrhizae etc. and is used for the treatment of the obese type fatty liver, cure mainly with the new drug research specification requirement according to its function and to have carried out main pharmacodynamics research, the result shows, make hyperlipidemia fatty liver model, gavage ethanol and inject carbon tetrachloride making hepatic injury fatty liver model, gavage ethionine making hepatic injury fatty liver model to the rat feeding high lipid food, observe the prevention and treatment of granule of the present invention respectively several model fatty livers.The filling stomach gave rat after granule of the present invention was made into suspension with distilled water, divide low dose of 5.25g crude drug/kg, three dosage groups such as middle dosage group 5.25g crude drug/kg, heavy dose of 10.50g crude drug/kg, the dosage of DONGBAO GANTAI is 1.00g/kg, the same the present invention of medication.The result shows, no matter the present invention be the prevention administration, or the treatment administration all can effectively reduce TC, TG, LDL-C level in liver weight, liver index, liver and the serum of fatty liver rat, effectively improve HDL-C content in liver and the serum simultaneously, the liver organization that pathological examination is also visible of the present invention group is similar with the normal control group, points out the present invention to have the good effect that prevents and treats experimental fatty liver.

Claims

1, a kind of medicine for the treatment of obese fatty liver is characterized in that it is the medicament of being made by the following weight proportion raw material:

2, the medicine of treatment obese fatty liver according to claim 1 is characterized in that described medicament is a granule.

3, the preparation method of the medicine of the described treatment obese fatty liver of claim 2 may further comprise the steps:

(1) gets Rhizoma Polygoni Cuspidati, Rhizoma Pinelliae Preparatum, Rhizoma Alismatis, Semen Persicae, Fructus Polygoni Orientalis, Radix Glycyrrhizae Six-element, add 5～12 times of amount 50～85% ethanol, soaked 1～12 hour, heating and refluxing extraction 2～4 times, each 0.5～4 hour, merge alcohol extract, decompression recycling ethanol and to be concentrated into relative density be 1.02～1.08, leave standstill, filter, it is 1.20～1.25 that filtrate decompression is concentrated into relative density, vacuum drying, be ground into fine powder, get extract powders such as Rhizoma Polygoni Cuspidati;

(2) get Rhizoma Curcumae, add the water of 6～14 times of amounts, extracted volatile oil 4～16 hours, it is standby to collect volatile oil; The medicinal liquid behind the oil is carried in leaching, and is centrifugal, and being concentrated into relative density is 1.20～1.25, and vacuum drying is ground into fine powder, gets the Rhizoma Curcumae extract powder; Get 6～10 times of amounts of volatile oil beta-schardinger dextrin-, put in 20～40 ℃ of water and make saturated aqueous solution, volatile oil is dropped in the saturated aqueous solution of beta-schardinger dextrin-, stir, cold preservation is filtered, and drying promptly gets the volatile oil inclusion complex;