CN101563092B - A composition comprising the extract of combined herbs for preventing and treating liver disease - Google Patents
A composition comprising the extract of combined herbs for preventing and treating liver disease Download PDFInfo
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Abstract
The present invention is related to a combined herb composition comprising herbs of Coriolus versicolor, Astragalus membranaceus Bunge, and additionally comprising at least one herb selected from group consisting of Schisandra chinensis, and Artemisia capillaris, according to the need for the prevention and treatment of liver disease and methods of using the above crude drug composition and pharmaceutical composition as hepato-protective agent.
Description
Technical field
The present invention relates to a kind of compositions that is used for hepatopathy prevention and treatment needs; It comprises the herb extracts of Coriolous Dersicolor (Fr.) Quel (Coriolusversicolor), the Radix Astragali (Astragalus membranaceus Bunge), Fructus Schisandrae Chinensis (Schisandra chinensis) and Herba Artemisiae Scopariae (Artemisia capillaris); The method that also relates to rough pharmaceutical composition more than the use, and as the pharmaceutical composition of liver protecting property reagent.
Background technology
Be exposed to (for example polluter, toxicant such as excessive consumption of alcohol, the smoking etc. of various adverse environments nowadays; And mental pressure; Mental pressure can be through having a rest and rehabilitation causes the for example generation of immune system disorder of other diseases but it can seriously be changed) the mankind in hepatopathy be one of disease of generation the most often.Existing report: because the damage of cell membrane, toxicant for example carbon tetrachloride, D-Gal etc. causes the toxicity (Brucker, J.V., Fund.Appl.Toxicology, 6, pp16-34,1986) in liver and the kidney.
Until now; Several medicines have been reported from the natural product source; It plays a role through suppressing free group regeneration, for example, separates the silymarin (silymarin from Silybum marianum Gaertn (Silybum marianum) [water flies jasmine (Carduus marianus)] fruit; SLM), it belongs to Compositae (Compositae); BDD (biphenyl dicarboxylic acid dimethyl ester) is for separating the synthetic analogues from the schisandrin (schizandrin) of Fructus Schisandrae Chinensis, or the like (CaragyA.B., Food Technology, 46, pp65-68,1992; Liang jun, Y., et al., Biochem.And Biophy.Res.Comm., 212, pp360-366,1995).
But, still have demand to develop a kind of effective and safe drugs that perhaps improve liver function with prevention of liver disease that are used to treat now.
Reported Coriolous Dersicolor (Fr.) Quel (a kind of mushroom; Belong to Aphyllophorales (Aphyllophorales); Be distributed in all over the world) comprise ergosterol, cupreol, coriolan (coriolan), Intracellular Polysaccharide of Poly-stictus Versicolor PS-K-D-glucosan and Sai Fu acid (thelphoric acid) and show (the Park Wan-Hee and Lee Ho-Deuk such as activity of antibacterial activity, anti-inflammatory activity, immune-enhancing activity, cholesterol reducing; Illustrated Book of KoreanMedicinal Mushrooms, Kyo-Hak Publishing Co., Ltd; P472,1st Ed.1999).
Reported that the Radix Astragali (it belongs to pulse family (Leguminosae)) comprises formoononetin (formononetin), isoliquiritigenin (isoliquiritigenin), glucuronic acid, choline, betanin, folic acid, 2 ', 4 '-dihydroxy-5,6-dimethoxy-isoflavone, kumatakenin (Kumatakenin) etc.; And show (Chung such as cardiac tonic effect, hypotensive activity, diuretic activity, hormonelike activity; B.S., et al., Illustrated Crude Drug Encyclopedia; Youngrim Publishing Co.Ltd.; 2nd Ed., p662-664,1998; Http:// www.tradimed.com).
It is first-class to have reported that Fructus Schisandrae Chinensis (it belongs to Magnoliaceae (Magnoliaceae)) comprises schisandrin, Ge Mixin (gomisin) A-Q, citral, α-fragrant cananga rare (ylangene), citric acid, malic acid, β-chamigrene (chamigrene), fatty oil, deoxidation schisandrol; And show vasodilator activity, hypotensive activity, (Chung such as the activity of reducing phlegm; B.S., et al., Illustrated Crude Drug Encyclopedia; YoungrimPublishing Co.Ltd.; 2nd Ed., p471-473,1998; Http:// www.tradimed.com).
Reported that Herba Artemisiae Scopariae (it belongs to Compositae) comprises escoparone (scoparone), chlorogenic acid, caffeic acid, pinene (pinene), capillin (capillin), capillen piece (capillene), capillarin (capillarin), stearic acid, Palmic acid etc.; And show (Chung such as hypotensive activity, diuretic activity, choleretic activity; B.S., et al., Illustrated Crude Drug Encyclopedia; Youngrim Publishing Co.Ltd.; 2nd Ed., p1016-1018,1998; Http:// www.tradimed.com).
But in above listed all documents (here being incorporated herein by reference), Shang Weiyou reports or discloses the therapeutic effects of above-described medical herbs combined extracts in hepatopathy.
Therefore; The inventor is intended to find to strengthen the effective herbal medicinal product of liver protecting property effect; And studying the pharmacological effect of above-described medical herbs combined extracts, the last inventor finds that the rough medicine of above-described combination is effective as liver protecting property reagent in prevention and treatment hepatopathy.
Summary of the invention
Technical problem
According to an aspect, the present invention provides a kind of pharmaceutical composition that is used to prevent and treat hepatopathy, and it comprises the extract of the combined herbs of Coriolous Dersicolor (Fr.) Quel, the Radix Astragali, Fructus Schisandrae Chinensis and Herba Artemisiae Scopariae.
The present invention also provides a kind of pharmaceutical composition, and it comprises the above extract as active component that can effectively prevent and treat hepatopathy dosage, and pharmaceutically acceptable carrier.
The present invention also provides a kind of method of treating hepatopathy in the mammal, thereby said method is protected hepatocyte treatment hepatopathy through said extracted thing and pharmaceutically acceptable carrier thereof to said administration effective dose.
The present invention also provides said extracted thing preparation to be used for treating or prevent the purposes of the medicine of the mankind or mammal hepatopathy.
The present invention also provides a kind of healthy functions food, and it comprises the said extracted thing as active component that can effectively prevent and improve hepatopathy dosage, and said extract prevents through the protection hepatocyte and improves hepatopathy.
Technical scheme
Therefore; The purpose of this invention is to provide a kind of pharmaceutical composition that is used to prevent and treat hepatopathy; It comprises the combined herbs that can effectively prevent and treat hepatopathy dosage as active component, and said combined herbs is made up of the Coriolous Dersicolor (Fr.) Quel and the Radix Astragali, and pharmaceutically acceptable carrier.
The present invention also provides a kind of pharmaceutical composition that comprises combined herbs that is used to prevent and treat hepatopathy, and it also comprises at least a medical herbs that is selected from Fructus Schisandrae Chinensis or Herba Artemisiae Scopariae except comprising above-mentioned medical herbs.
Another object of the present invention provides the purposes that the preparation of above-mentioned herb extracts is used for treating or prevent the medicine of the mankind or mammal hepatopathy.
Another object of the present invention provides a kind of method of treating hepatopathy in the mammal, and said method is through to the said extracted thing of said administration effective dose and pharmaceutically acceptable carrier thereof and the liver protecting cell.
In preferred embodiment of the present invention; Extract disclosed herein comprises the extract of combined herbs, i.e. the Coriolous Dersicolor (Fr.) Quel and the Radix Astragali, and it mixes with the ratio (w/w%) based on every kind of medical herbs dry weight; Preferred ratio is between 0.1-10: 1; 0.5-5 more preferably: 1,1-2 more preferably again: 1, prevention in the present invention or treatment hepatopathy.
In another preferred embodiment of the present invention; Extract disclosed herein comprises the extract of combined herbs, i.e. Coriolous Dersicolor (Fr.) Quel, the Radix Astragali and Fructus Schisandrae Chinensis, and it mixes with the ratio (w/w%) based on every kind of medical herbs dry weight; Preferred ratio is between 0.1-10: 0.1-10: 1; 0.5-5: 0.5-5 more preferably: 1,1-2: 1-2 more preferably again: 1, in the present invention with prevention or treatment hepatopathy.
In another preferred embodiment of the present invention; Extract disclosed herein comprises the extract of combined herbs, i.e. Coriolous Dersicolor (Fr.) Quel, the Radix Astragali, Fructus Schisandrae Chinensis and Herba Artemisiae Scopariae, and it mixes with the ratio (w/w%) based on every kind of medical herbs dry weight; Preferred ratio is between 0.1-10: 0.1-10: 0.1-10: 1; 0.5-5: 0.5-5: 0.5-5 more preferably: 1,1-2: 1-2: 1-2 more preferably again: 1, in the present invention with prevention or treatment hepatopathy.
Adapt with one aspect of the present invention, a kind of healthy functions food be provided, its comprise can effectively prevent and improve hepatopathy dosage the said extracted thing as active component, prevent and improve hepatopathy through the liver protecting cell.
Here " hepatopathy " comprises fatty liver, acute or chronic hepatitis, hepatomegaly, liver abscess, liver cirrhosis and hepatocarcinoma, is preferably fatty liver, liver cirrhosis and hepatitis, more preferably alcoholic fatty liver, non-alcoholic fatty liver disease, diabetic fatty liver and hepatitis.
Can be used for medical herbs of the present invention and comprise it obviously being generic plant for a person skilled in the art, and it has been used for same or similar purpose, and can be replaced with prevention and treatment hepatopathy.
Compositions according to the invention is used with its form of pulverizing, extraction form or dry extract form.
More than the extraction form of rough pharmaceutical composition can use distilled water, low-carbon alcohols (like methanol, ethanol etc.) or its mixture, be preferably water and obtain through extracting.
The term here " extract " comprises CE, low-carbon alcohols insolubility component extract and non-polar solven soluble extract.
The term here " crude extract " is included in distilled water, C1-C4 low-carbon alcohols (like methanol, ethanol etc.) or its mixture, is preferably the mixed solution of second alcohol and water, more preferably soluble extract in the alcoholic acid aqueous solution of 50-90%.
The term here " low-carbon alcohols insolubility component extract " comprises the extract through following steps preparations: with the low-carbon alcohol solution mixed solution of second alcohol and water for example, be preferably the alcoholic acid extraction with aqueous solution crude extract of 50-90% to separate low-carbon alcohols soluble component and low-carbon alcohols insolubility composition; And collect low-carbon alcohols insolubility component extract according to the invention.
The term here " non-polar solven soluble extract " comprises the extract through following steps preparations: with non-polar solven for example hexane, chloroform, dichloromethane or ethyl acetate, be preferably hexane and extract crude extract; And collect non-polar solven soluble extract according to the invention.
In the most preferred specific embodiment of the present invention; In compositions of the present invention, " extract " of combined herbs is made up of following: the low-carbon alcohols insolubility composition of the crude extract of Coriolous Dersicolor (Fr.) Quel, the Radix Astragali and Herba Artemisiae Scopariae and the non-polar solven soluble extract of Fructus Schisandrae Chinensis; But not in order to limit the present invention.
The pharmaceutical composition that is used to treat hepatopathy can contain based on composition total weight about 0.01 to 95w/w%, be preferably 0.5 to 80w/w% above-mentioned herbal-composition according to the invention.
Can prepare herbal-composition of the present invention through the following preferred specific embodiment.
For the present invention, above-mentioned rough pharmaceutical composition can prepare through following program: with medical herbs, i.e. and Coriolous Dersicolor (Fr.) Quel, the Radix Astragali, Fructus Schisandrae Chinensis and Herba Artemisiae Scopariae washing, broken, dry and mix with suitable ratio (w/w).Said mixture is pulverized to obtain the form of pulverizing of rough pharmaceutical composition.
With above-mentioned rough pharmaceutical composition of pulverizing and 5-20 doubly, the distilled water, alcohol (for example methanol, ethanol etc.) or its mixture that are preferably 10-15 times of volume mix, and are preferably with the mixture of distilled water or second alcohol and water and mix; Then, 0 to room temperature, be preferably enfleurage (enfleurage) in 4-6 ℃ the temperature range; Continue 12 to 48 hours, be preferably 20-24 hour, perhaps; At 80 to 120 ℃, the temperature range internal reflux that is preferably more than 100 ℃ extracts heating, continues 1-24 hour; Be preferably 2-5 hour, carry out 2-5 time; Perhaps, through ultrasonic, reflux or conventional the extraction to obtain the rough pharmaceutical composition of aqueous extract form.
In addition, filter and under 80-90 ℃ of decompression, herb extracts is concentrated.Extract passes through azeotropic distillation 1-5 time with the water of 10-60 times of volume, carries out dry to obtain the dry crude extract of rough pharmaceutical composition then through lyophilizing or vacuum drying.
" the low-carbon alcohols insolubility component extract " of each medical herbs can be through following steps preparations: with the crude extract of above-mentioned steps preparation through the low-carbon alcohol solution (mixture solution of second alcohol and water for example; The alcoholic acid aqueous solution of 50-90% more preferably) extract, its consumption be 1-8 times based on crude extract weight; Place separately under the room temperature to continue 12-48 hour, be preferably 18-24 hour, to separate low-carbon alcohols soluble component and low-carbon alcohols insolubility composition; And collect low-carbon alcohols insolubility component extract according to the invention.
" the non-polar solven soluble extract " of each medical herbs can be through following steps preparations: the crude extract of above-mentioned steps preparation is separated through non-polar solven, and consumption be based on the 1-8 of crude extract volume doubly, is preferably 2-5 times; And collect non-polar solven soluble extract according to the invention.
Another object of the present invention provides the method for preparing the said extract of the invention described above is used to prevent or treat hepatopathy with preparation effective composition.
Another object of the present invention provides a kind of pharmaceutical composition that is used to prevent and treat hepatopathy, its comprise the form of pulverizing that obtains through said method, extract above-mentioned rough drug extract form or the dry extract form as active component.
Compositions according to the invention through method for preparing significance in rat experiment model suppresses GOT, GPT, the LDL-cholesterol in the liver organization, the expression and the hepatic fibrosis of HMG-CoA reductase gene, and increases HDL-level of cholesterol in the blood.When measuring the oral acute toxicity of extract, do not find its effect for discovery total in mortality rate, clinical sign, body weight change and the postmortem.
The pharmaceutical composition that is used to treat hepatopathy can contain based on composition total weight about 0.01 to 95w/w%, be preferably 0.5 to 80w/w% above-mentioned of the present invention rough pharmaceutical composition.
Another object of the present invention provides a kind of liver protecting property reagent, its comprise can effectively prevent and treat hepatopathy dosage the said extracted thing as active component.
Another object of the present invention provides a kind of method of treating hepatopathy in the mammal, and said method is the said extracted thing and the pharmaceutically acceptable carrier thereof of said administration effective dose.
Consistent with method for using, compositions of the present invention also can comprise conventional carrier, adjuvant or diluent.Preferably, according to consumption and method for using, said carrier is used as suitable material, but is not restrictive.Suitable diluent is listed in the record content among Remington ' the s Pharmaceutical Science (Mack Publishing co, Easton PA).
Below, following formulation method and excipient are exemplary and never be restriction the present invention.
Rough pharmaceutical composition according to the invention can be used as pharmaceutical composition to be provided; Said pharmaceutical composition comprises pharmaceutically acceptable carrier, adjuvant or diluent; For example, lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltose alcohol, starch, acacia gum, bath hydrochlorate, gelatin, calcium phosphate, calcium silicates, cellulose, methylcellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, Muscovitum, magnesium stearate and mineral oil.Preparation can comprise filler, anti-agglutinant, lubricant, humidizer, flavouring agent, emulsifying agent, antiseptic etc. in addition.Through using any program well known in the art, compositions according to the invention can be made into preparation so that rapid release, slow release or the extended release of active component to be provided after using to patient.
For example, in compositions oil-soluble according to the invention, propylene glycol or other solvents, these solvents are normally used for producing injection.The example of suitable carriers comprises: normal saline, Polyethylene Glycol, ethanol, vegetable oil, isopropyl myristate etc., but be not limited to these.Use for the part, chemical compound according to the invention can be made into ointment or Emulsion.
The pharmaceutical preparation that contains rough pharmaceutical composition can any prepare, for example oral agents form (powder, tablet, capsule, soft capsule, aqueous medicine, syrup, elixir, pill, powder, sachet (sachet), granule) or local prepared product (Emulsion, ointment, washing liquid, gel, balsam (balm), patch (patch), ointment (paste), spray solution, aerosol etc.), suppository or aseptic injection preparation (solution, suspension, emulsion).
The pharmaceutical dosage form of rough pharmaceutical composition according to the invention can its pharmaceutically acceptable salt form provide, can use separately or with the suitable use of uniting, and use with other pharmaceutically active compounds combinations.The required dosage of the present composition is variable, depends on individual situation and body weight, seriousness, medicament forms, drug delivery route and time, and can be selected by those skilled in the art.But, in order to obtain required effect, to recommend with 0.01-10g/kg weight every day usually, the dosage that is preferably 1-5g/kg weight is used compositions according to the invention.Can every day single agent of dosage or multi-agent use.As for compositions, rough pharmaceutical composition should be with the 0.01-80% weight based on composition total weight, and preferred 0.5-50% weight appears.
Pharmaceutical composition according to the invention can use to animal individual by all means, for example mammal (rat, mice, domestic animal or the mankind).Considered used mode of administration, for example, in oral, rectum or intravenous, intramuscular, subcutaneous, Intradermal, the fallopian tube, cerebral dura mater or intracerebroventricular injection.
Consistent with one aspect of the present invention, a kind of healthy functions food is provided, its comprise can effectively prevent and improve hepatopathy dosage the said extracted thing as active component, prevent and improve hepatopathy through the liver protecting cell.
The rough pharmaceutical composition of healthy functions food of the present invention uses with its form of pulverizing, extraction form or dry extract form.
The healthy functions food of the present invention that is used to prevent and improves hepatopathy can contain the about 0.01-95w/w% based on composition total weight, the rough pharmaceutical composition of the invention described above of preferred 0.5-80w/w%.
Above-mentioned rough pharmaceutical composition can make an addition to food, additive or beverage with prevention with improve hepatopathy.Wherein, In order to prevent and improve the purpose of hepatopathy, the dosage of the above-mentioned rough pharmaceutical composition in food or the beverage is the about 0.1-15w/w% that is used for the food gross weight of health food compositions, is preferably 1-10w/w%; In the 100ml healthy beverage compositions is 1-30g, is preferably 3-10g.
In view of healthy beverage compositions of the present invention contain represent ratio above-mentioned rough pharmaceutical composition as main component; So to the not special restriction of other liquid components, wherein other compositions can be for example conventional beverage such as various deodorant or natural carbohydrate.The example of above-mentioned natural carbohydrate is for example glucose, a fructose etc. of monosaccharide; Disaccharide is maltose, sucrose etc. for example; Conventional sugar is like dextrin, cyclodextrin; With sugar alcohol for example xylitol and erythritol etc.As the deodorizer except above-mentioned; Can use for example for example Lai Wodisai A (levaudioside A), glycyrrhizin etc. of Tao Mating (taumatin), Flos Chrysanthemi extract of natural deodorant valuably, and synthetic deodorizer for example glucide, L-aspartyl-L-phenylalanine Methylester etc.The dosage of above-mentioned natural carbohydrate is generally and is about 1-20g in this beverage composition for treating dental erosion of 100ml, is preferably 5-12g.
Other compositions that gone out beyond the above-mentioned composition are used carburization agent in various nutrients, vitamin, mineral or electrolyte, synthetic flavouring agent, coloring agent and refining agent (if cheese chocolate etc.), pectic acid and salt, Brown algae calculation and salt thereof, organic acid, protectiveness colloid adsorbent, pH controlling agent, stabilizing agent, antiseptic, glycerol, alcohol, the soda pop etc.Composition except above-mentioned can be fruit juice, fruit drink and the vegetable beverage that is used to prepare natural fruit juice, and wherein composition can use or make up use separately.The ratio of composition is not so important, but is typically about this compositions of the every 100w/w% of 0-20w/w%.
The addible example that contains the food of above-mentioned rough pharmaceutical composition is that various foods, beverage, chewing gum, vitamin complex, health improve food etc.
For a person skilled in the art, can make various modifications and change to compositions of the present invention, purposes and prepared product and do not break away from essence of the present invention.
Beneficial effect
Combined herbs compositions according to the invention demonstrates strong depression effect for the GOT, GPT, cholesterol, triglyceride, the LDL-cholesterol levels that raise; And the HDL-cholesterol levels that reduces demonstrated the effect of increase and prevention and treatment liver cirrhosis and fatty liver.
Compositions according to the invention is useful in prevention and treatment hepatopathy, can be used as safe and efficient liver protecting property reagent.
Description of drawings
Through the following specifically describes and accompanying drawing with clearer understanding above and other purposes, characteristics and other advantages of the present invention, wherein:
Fig. 1 has shown the variation of the GOT level of the various extract-treated groups of preparation in the comparing embodiment 1 in the CCL4 inducing mouse.
Fig. 2 has shown the variation of the GPT level of each extract-treated groups of preparation in the comparing embodiment 1 in the CCL4 inducing mouse.
Fig. 3 has shown the varying effect of the GOT level of the combined extracts processed group for preparing among the embodiment 1 in the inductive hepar damnification prophylaxis model of CCL4.
Fig. 4 has shown the varying effect of the GPT level of the combined extracts processed group for preparing among the embodiment 1 in the inductive hepar damnification prophylaxis model of CCL4.
Fig. 5 has shown the varying effect of the GOT level of the combined extracts processed group for preparing among the embodiment 1 in the inductive hepar damnification treatment of the CCL4 model.
Fig. 6 has shown the varying effect of the GPT level of the combined extracts processed group for preparing among the embodiment 1 in the inductive hepar damnification treatment of the CCL4 model.
Fig. 7 has shown the variation of the level of GOT and GPT in the inductive Hepatocirrhosis Model of DMN.
Fig. 8 has shown the effect to collagen distribution in the inductive Hepatocirrhosis Model of DMN.
Fig. 9 has shown the GOT of each extract-treated groups that comparing embodiment in the inductive rat fat liver of ethanol 2 and embodiment 2 are prepared and the variation of GPT level.
Figure 10 has shown in the inductive rat fat liver of ethanol the variation with the blood cholesterol levels of each prepared extract-treated groups of comparing embodiment 2 and embodiment 2.
Figure 11 has shown the effect of the prepared extract of comparing embodiment in the inductive rat fat liver of ethanol 2 and embodiment 2 for the variation of blood triglyceride.
Figure 12 has shown the effect that comparing embodiment in the inductive rat fat liver of ethanol 2 and embodiment 2 prepared extracts change for blood HDL-cholesterol.
Figure 13 has shown the effect that comparing embodiment in the inductive rat fat liver of ethanol 2 and embodiment 2 prepared extracts change for blood LDL-cholesterol.
Figure 14 has shown the effect that comparing embodiment in the inductive rat fat liver of ethanol 2 and embodiment 2 prepared extracts change for the liver cholesterol level.
Figure 15 has shown the effect that comparing embodiment in the inductive rat fat liver of ethanol 2 and embodiment 2 prepared extracts change for the liver triglyceride levels.
Figure 16 has shown the effect of the prepared extract of embodiment in the inductive rat fat liver of ethanol 2 for the hepatic tissue morphological change.
Figure 17 has shown that embodiment 2 prepared extracts are expressed the effect that changes in the inductive rat fat liver of ethanol for the HMG-CoA reductase gene.
The specific embodiment
Preferred forms
Following examples and experimental example are in order to further specify the present invention rather than to limit its scope.
The invention pattern
The preparation of comparing embodiment 1 each herb extracts (1)
1-1. the preparation of Coriolous Dersicolor (Fr.) Quel crude extract 1 (CV30E)
500g Coriolous Dersicolor (Fr.) Quel washing with buying the Kyung-dong market from the Soul adds the 10L distilled water.In the first step, with solution at 100 ℃ with twice of distilled water reflux, extract.The extract that the first step is obtained filters and concentrates to prepare the 800ml concentrate at 105 ℃.With concentrate 60 ℃ of dryings with the dry crude extract (productive rate: 12.4%) of the Coriolous Dersicolor (Fr.) Quel that obtains 62.0g.
1-2. Radix Astragali crude extract (AM80M)
With the 800g Radix Astragali washing of buying Kyung-dong market, add the alcoholic solution of 10L 70% from the Soul.In the first step, with solution at 100 ℃ with twice of distilled water reflux, extract.The extract that the first step is obtained filters and concentrates to prepare the 750ml concentrate at 105 ℃.With concentrate 60 ℃ of dryings with the dry crude extract (productive rate: 19.2%) of the Radix Astragali that obtains 153.6g.
1-3. Fructus Schisandrae Chinensis crude extract (SC80M)
With the 500g Fructus Schisandrae Chinensis washing of buying Kyung-dong market, add the alcoholic solution of 10L 70% from the Soul.In the first step, with solution at 100 ℃ with twice of distilled water reflux, extract.The extract that the first step is obtained filters and concentrates to prepare the 900ml concentrate at 105 ℃.With concentrate 60 ℃ of dryings with the dry crude extract (productive rate: 36.6%) of the Fructus Schisandrae Chinensis that obtains 183.0g.
1-4. Herba Artemisiae Scopariae crude extract (ACDW)
500g Herba Artemisiae Scopariae washing with buying the Kyung-dong market from the Soul adds the 10L distilled water.In the first step, with solution at 100 ℃ with twice of distilled water reflux, extract.The extract that the first step is obtained filters and concentrates to prepare the 650ml concentrate at 105 ℃.With concentrate 60 ℃ of dryings with the dry crude extract (productive rate: 18.3%) of the Herba Artemisiae Scopariae that obtains 91.5g.
The preparation (2) of comparing embodiment 2. each herb extracts
2-1. the soluble extract of Coriolous Dersicolor (Fr.) Quel low-carbon alcohols (CO)
1000g Coriolous Dersicolor (Fr.) Quel washing with buying the Kyung-dong market from the Soul adds the 10L distilled water.In the first step, with solution 100 ℃ with distilled water reflux, extract, twice, continue 2 hours.The extract that the first step is obtained filters and concentrates to prepare the 1000ml concentrate at 105 ℃.Ethanol through adding 95% in concentrate is processed 70% alcoholic solution; Place following 12 hours of room temperature to separate the supernatant layer and the beds of precipitation separately this alcoholic solution of 70%; With being deposited in the exsiccant low-carbon alcohols soluble extract of 60 ℃ of dryings with the Coriolous Dersicolor (Fr.) Quel that obtains 31.5g (productive rate: 3.15%, below be called CO).
2-2. Radix Astragali crude extract (AS)
With the 1000g Radix Astragali washing of buying Kyung-dong market, add the alcoholic solution of 10L 95% from the Soul.In the first step, with solution 95 ℃ with distilled water reflux, extract, twice, continue 2 hours.Concentrate 3 hours with preparation 1000ml concentrate with the extract filtration of first step acquisition and at 105 ℃.With concentrate 60 ℃ of dryings with the dry crude extract of the Radix Astragali that obtains 80.3g (productive rate: 8.03%, below be called AS).
2-3. Fructus Schisandrae Chinensis non-polar solven soluble extract (AR)
With the 1000g Fructus Schisandrae Chinensis washing of buying Kyung-dong market, add the alcoholic solution of 10L 95% from the Soul.In the first step, with solution 95 ℃ with distilled water reflux, extract, twice, continue 2 hours.The extract that the first step is obtained filters and concentrates to prepare the 1000ml concentrate at 105 ℃.The hexane that adds equivalent to be to separate water layer and hexane dissolvable layer, collects the hexane dissolvable layer with the hexane soluble extract of acquisition Fructus Schisandrae Chinensis (productive rate: 1.21%, below be called AR).
2-4. the soluble extract of Herba Artemisiae Scopariae low-carbon alcohols (SC)
1000g Herba Artemisiae Scopariae washing with buying the Kyung-dong market from the Soul adds the 10L distilled water.In the first step, with solution 100 ℃ with distilled water reflux, extract, twice, continue 2 hours.The extract that the first step is obtained filters and concentrates to prepare the 1000ml concentrate at 105 ℃.Ethanol through adding 95% in concentrate is processed 70% alcoholic solution; Place following 12 hours of room temperature to separate the supernatant layer and the beds of precipitation separately this alcoholic solution of 70%; With being deposited in the exsiccant low-carbon alcohols soluble extract of 60 ℃ of dryings with the Herba Artemisiae Scopariae that obtains 119.7g (productive rate: 11.97%, below be called SC).
The preparation of embodiment 1. invention combination preparations (1)
1-1. the preparation of invention H1
The extract of each prepared in the comparing embodiment 1 Coriolous Dersicolor (Fr.) Quel and the Radix Astragali is mixed with preparation invention combination preparation (below be called H1) with 1: 1 weight rate.
1-2. the preparation of invention H2
The extract of each Coriolous Dersicolor (Fr.) Quel, the Radix Astragali and Fructus Schisandrae Chinensis prepared in the comparing embodiment 1 is mixed with preparation invention combination preparation (below be called H2) with 1: 1: 1 weight rate.
1-3. the preparation of invention H3
The extract of each Coriolous Dersicolor (Fr.) Quel, the Radix Astragali and Herba Artemisiae Scopariae prepared in the comparing embodiment 1 is mixed with preparation invention combination preparation (below be called H3) with 1: 1: 1 weight rate.
1-4. the preparation of invention H4
With the extract of each Coriolous Dersicolor (Fr.) Quel, the Radix Astragali, Fructus Schisandrae Chinensis and Herba Artemisiae Scopariae prepared in the comparing embodiment 1 with 1: 1: 1: 1 weight rate mixes with preparation invention combination preparation (below be called H4).
The preparation of embodiment 2. invention combination preparations (2)
2-1. the preparation of invention HF1
The extract of each prepared in the comparing embodiment 2 Coriolous Dersicolor (Fr.) Quel and the Radix Astragali is mixed with preparation invention combination preparation (below be called HF-1) with 1: 1 weight rate.
2-2. the preparation of invention HF2
The extract of each Coriolous Dersicolor (Fr.) Quel, the Radix Astragali and Fructus Schisandrae Chinensis prepared in the comparing embodiment 2 is mixed with preparation invention combination preparation (below be called HF2) with 1: 1: 1 weight rate.
2-3. the preparation of invention HF3
The extract of each Coriolous Dersicolor (Fr.) Quel, the Radix Astragali and Herba Artemisiae Scopariae prepared in the comparing embodiment 2 is mixed with preparation invention combination preparation (below be called HF3) with 1: 1: 1 weight rate.
2-4. the preparation of invention HF4
With the extract of each Coriolous Dersicolor (Fr.) Quel, the Radix Astragali, Fructus Schisandrae Chinensis and Herba Artemisiae Scopariae prepared in the comparing embodiment 2 with 1: 1: 1: 1 weight rate mixes with preparation invention combination preparation (below be called HF4).
The effect of the inductive chronic hepatic injury of CCl4 in 1. pairs of rat models of experimental example
For the depression effect of hepatic injury, carried out following experiment in order to study the invention combined extracts (with comparing in the comparing embodiment 1) that obtains among the embodiment 1.
1-1. reagent and laboratory animal
CCl4 (Sigma Co.), olive oil (Sigma Co.), alanine aminotransferase (ALT, GPT, Stanbio Co.) and aspartate amino transferase (AST, GOT,, Stanbio Co.) buy from commercial company, to be used for experiment.
Use in the experiment male Sprague-Dawley rat (the about 200g of body weight) (Daehan Biolink Co.Ltd., Korea), be placed on can freely obtain feedstuff (Harlan, teklan, USA) and drinking-water.All animals remain in the controlled environment, and temperature is 21 ℃-24 ℃, and humidity is 60%-80%, and 12 hours illumination-12 hour dark cycle continued for 1 week before use at least.Every group average weight is optimized according to every group, and every group has 10.
1-2. each medical herbs is to the effect of the inductive chronic hepatic injury of CCl4
In order to assess the effect for hepatic injury, normal group is only with saline treatment.The mixture solution (1: 3) of olive oil and CCl4 is gone into every experimental rat through peritoneal injection, and dosage is 1.0ml/kg, continues 3 days, induces acute liver poisoning to be used as matched group with this.Induced back 1 hour, administered through oral behind the additional saline of the extract in the comparing embodiment 1 of various concentration is used to rat, dosage is 1.0ml/kg, continues three days, and this is a testing group; For negative control group, a saline treatment with equivalent.Induced back 18 hours, vein is collected blood sample under the eye socket, under the 3000rpm centrifugal 20 minutes.Use BT2000+ device (SEAC Co.) to measure each GOT and the GPT level of each sample.
As illustrated in fig. 1 and 2; The normal group of only handling with saline solution demonstrates the GOT level of about 200U/I and the GPT level of 74U/I, and the matched group of handling with olive oil and CCl4 mixed solution (1: 1) demonstrates the GOT level of about 461U/I and the GPT level of 168U/I.But the testing group of handling with each herb extracts demonstrates liver protecting property activity, and it is Coriolous Dersicolor (Fr.) Quel in proper order, Fructus Schisandrae Chinensis, the Radix Astragali and Herba Artemisiae Scopariae (seeing Fig. 1 and 2).
Therefore confirm: invention extract of the present invention is effective for relaxing liver function.
1-3. combination preparation is for the effect of the inductive chronic hepatic injury of CCl4
In order to assess the effect for hepatic injury, normal group is only with saline treatment.The mixture solution (1: 1) of olive oil and CCl4 is gone into every experimental rat through peritoneal injection, and dosage is 1.0ml/kg, continues 3 days, induces acute liver poisoning to be used as matched group with this.Induced back 1 hour, with the invention combined extracts among the embodiment 1 of various concentration, administered through oral was used to rat after promptly H1, H2, H3 and H4 replenished saline, and dosage is 1g/60kg, continues three days, and this is a testing group; For negative control group, a saline treatment with equivalent.Induced back 18 hours, vein is collected blood sample under the eye socket, under the 3000rpm centrifugal 20 minutes.Use BT2000+ device (SEAC Co.) to measure each GOT and the GPT level of each sample.
Shown in Fig. 3 and 4, the matched group of handling with olive oil and CCl4 mixed solution (1: 1) demonstrates the GOT level of about 462U/I and the GPT level of 186U/I.But the testing group of handling with H1 demonstrates the GOT level of about 355U/I and the GPT level of 142.1U/I.Similar in the level of GOT and GPT and the H3 processed group in the H2 processed group, it is active to demonstrate stronger liver protecting property with respect to the H1 processed group.But the H4 processed group demonstrates the strongest liver protecting property active (seeing Fig. 3 and 4) in them.
Therefore confirm: invention combined extracts of the present invention is effective for treatment and prevention of liver disease.
1-4. combination preparation is for the effect of the inductive chronic hepatic injury of CCl4
In order to assess the effect for hepatic injury, normal group is only with saline treatment 4 days.The mixture solution (1: 1) of olive oil and CCl4 is gone into every experimental rat through peritoneal injection, and dosage is 1.0ml/kg, continues 3 days, induces acute liver poisoning to be used as matched group with this.Induced back 1 hour, with the invention combined extracts among the embodiment 1 of various concentration, administered through oral was used to rat after promptly H1, H2, H3 and H4 replenished saline, and dosage is 1g/60kg, continues four days, and this is a testing group; For negative control group, a saline treatment with equivalent.In the last day of test, from the laboratory animal of anesthesia, collect 1.5ml blood, and through heavily perfusion is fixing, under the 3000rpm centrifugal 20 minutes.Use CH100+ device (SEAC Co.) to measure each GOT and the GPT level of each sample.
As illustrated in Figures 5 and 6, the matched group of handling with olive oil and CCl4 mixed solution (1: 1) demonstrates the GOT level of about 488U/I and the GPT level of 201.4U/I.But that the testing group of handling with H1, H2 and H3 demonstrates respectively is about 347.6,304.1, the GOT level and 136.4,99.2 of 107.9U/I, the GPT level of 97.3U/I.Similar in the level of GOT and GPT and H2 and the H3 processed group in the H4 processed group, demonstrate great processing active (seeing Fig. 5 and 6) than H2 and H3 processed group.
The effect of the inhibition of collagen distribution and GOT and GPT level in 2. pairs of rat models of experimental example
In order to study the property the improved effect of the invention combined extracts that obtains among the embodiment 1, carried out following experiment.
2-1. reagent and laboratory animal
DMN (N-nitrosodimethylamine, Sigma Co.), alanine aminotransferase (ALT, GPT, StanbioCo.) and aspartate amino transferase (AST, GOT, Stanbio Co.) buy from commercial company, to be used for experiment.
Use Wister rat (the about 270g of body weight) in the experiment, be placed on can freely obtain feedstuff (Harlan, teklan, USA) and drinking-water.All animals remain in the controlled environment, and temperature is 21 ℃-24 ℃, and humidity is 60%-80%, and 12 hours illumination-12 hour dark cycle continued for 1 week before use at least.
2-2. effect to the inhibition of collagen distribution and GOT and GPT level
In order to assess the effect for liver cirrhosis, the DMN with 1% (N-nitrosodimethylamine) goes into every experimental rat through peritoneal injection, and dosage is 40mg/kg/ days, continues 3 days, induces liver cirrhosis with this.The invention combined extracts of preparation among the embodiment 1 is suspended in saline solution, and administered through oral is used to rat, and dosage is 1g/60kg, continues for two weeks, and this is a testing group; For negative control group, a saline treatment with equivalent.In the last day of test, from the laboratory animal of anesthesia, collect 1.5ml blood, and through heavily perfusion is fixing, under the 3000rpm centrifugal 20 minutes.Use CH100+ device (SEAC Co.) to measure each GOT and the GPT level of each sample.
In order to measure the distribution of collagen in the hepatic tissue, use Masson trichrome stain method, it dyes the collagen part; Isolating hepatic tissue is embedded automatic fabric analysis appearance (Citadel 2000, Shandon Co.), and using-system microtome (LEICA RM2145) is cut into the sheet of 4 microns width.Each tissue is chosen 5 damages, confirms the fibrosis ratio of this damage through the imaging analysis system.Calculate average rate value and be converted into collagen quantity.
As shown in Figure 7, with GOT and GPT level in the group significance inhibition hepatic injury rat model of the invention extract-treated of acquisition among the embodiment 1.It is active that H2 and H3 processed group demonstrate stronger inhibition than H1 processed group, and the H4 processed group demonstrates the strongest activity (Fig. 7 is seen in significance: p＜0.0001) in testing group.
And the collagen quantity in the group of handling with invention extract H1, H2, H3 and the H4 that obtains among the embodiment 1 is respectively 1.83,1.5,1.33 and 1.66, and matched group and normal group are respectively 2.44 and 1.33 (see figure 8)s.
Therefore confirm: invention combined extracts of the present invention is significantly effectively for the hepatic fibrosis process.
Experimental example 3. is for the effect of the inductive fatty liver of ethanol in the rat model
In order to study among the embodiment 2 the invention combined extracts that obtains depression effect (with comparing in the comparing embodiment 2), carried out following experiment for fatty liver.
3-1. laboratory animal and pretreatment
(Samtaco Co.Ltd. Korea), is placed on and can freely obtains feedstuff and drinking-water to use male Sprague-Dawley rat (the about 200g of body weight) in the experiment.All animals remain in the controlled environment, and temperature is 22 ± 2 ℃, and humidity is 60 ± 5%, 12 hours illumination-12 hour dark cycle, continue for 1 week at least before use.Every group average weight is optimized according to every group, and every group has 10.
3-2. pretreatment
For the induced lipolysis liver, animal feed (AIN 76, contain 1% cholesterol, Feedlab Co.Ltd.) administered through oral was used 21 days to experimental rat.In addition, from raising beginning in the 8th day, administered through oral is used 35% ethanol to experimental rat, to be used as matched group; From raising beginning in the 10th day, prepared extract administered through oral among comparing embodiment 2 and the embodiment 2 to be used to experimental rat, dosage is 50mg/kg.After Orally administered 21 days, with the etherization laboratory animal to be used for following experiment.
3-3. effect to GOT in the fatty liver and GPT
In order to measure the effect of invention combined extracts prepared among the embodiment 2 for blood GOT in the fatty liver and GPT concentration change; According to document (Bergmeyer HU; Scheibe P; Wahlefeld AW:optimization of methods for asparate aminotransferase and alanine aminotransferase.Clin Chem 24:58,1978) program in has been carried out following test.
After having carried out among the 3-2 similarly step, collect the blood of the laboratory animal of anesthesia.Under the 4550xg centrifugal 20 minutes.Use BT2000+ device (SEAC Co.) to measure each GOT and GPT level in the serum.
As shown in Figure 9, the testing group of handling with each medical herbs of preparation in the comparing embodiment 2 can not significantly reduce the GOT and the GPT level of 1% cholesterol and the inductive rising of 35% ethanol; Yet; The testing group of handling with the combined herbs of preparation among the embodiment 2 has significantly reduced the level of GOT and GPT; Wherein, In the inductive fatty liver model of ethanol, the HF4 processed group demonstrates for the GOT and the strongest reduction effect (GOT:131.2mg/dl, GPT:89.6mg/dl) (see figure 9) of GPT level that raise.
3-4. effect to serum lipid concentrations in the fatty liver
In order to measure the effect that changes for serum lipid concentrations in the fatty liver; According to document (Trinder, P.Determination of glucose in blood using glucose oxidase with an alternative oxygenacceptor.Ann Clin Bio Chem.6; 24-27,1969) program in has been carried out following test.
After having carried out among the 3-2 similarly step, collect the blood of the laboratory animal of anesthesia.Under the 4550xg centrifugal 20 minutes.Use BT2000+ device (SEAC Co.) to measure the level of each cholesterol, triglyceride, HDL and LDL in the serum.
The result of cholesterol levels
Shown in figure 10, (65.6mg/dl) compares with untreated normal group, and the blood cholesterol levels of the matched group of handling with 1% cholesterol and 35% ethanol increases to 2 times (158.1mg/dl); Yet; Group with the extract-treated of preparation among comparing embodiment 2 and the embodiment 2 demonstrates remarkable reduction effect for the cholesterol levels that raises; Wherein, In the inductive fatty liver model of ethanol, HF3 processed group (91.5mg/dl) and HF4 processed group (88.2mg/dl) demonstrate for the strongest reduction effect (see figure 10) of blood cholesterol levels that raises.
The result of triglyceride levels
Shown in figure 11, (63.6mg/dl) compares with untreated normal group, and the blood triglyceride level of the matched group of handling with 1% cholesterol and 35% ethanol increases to 3 times (173.2mg/dl); Yet; Group with the extract-treated of preparation among comparing embodiment 2 and the embodiment 2 demonstrates remarkable reduction effect for the triglyceride levels that raises; Wherein, In the inductive fatty liver model of ethanol, HF1 processed group (120.2mg/dl) demonstrates for the strongest reduction effect (seeing Figure 11) of blood triglyceride level that raises.
The result of HDL-cholesterol and LDL-cholesterol levels
Shown in figure 12, (53.8mg/dl) compares with untreated normal group, demonstrates the blood HDL-cholesterol levels (55.4mg/dl) of reduction with the matched group of 1% cholesterol and the processing of 35% ethanol; Yet, demonstrate remarkable rising effect (seeing Figure 12) for the HDL level that reduces with the group of the extract-treated of preparation among comparing embodiment 2 and the embodiment 2.
Shown in figure 13, (53.2mg/dl) compares with untreated normal group, and the blood LDL-cholesterol levels of the matched group of handling with 1% cholesterol and 35% ethanol increases to 3 times (168.7mg/dl); Yet, demonstrate remarkable reduction effect with the group of the extract-treated of preparation among comparing embodiment 2 and the embodiment 2 for the LDL level that raises, similar with the result among Figure 10; Wherein, in the inductive fatty liver model of ethanol, HF4 processed group (114.8mg/dl) demonstrates for the strongest reduction effect (seeing Figure 13) of blood LDL level that raises.
Confirm from the result of above description: the extract of preparation demonstrates strong reduction effect for the cholesterol, triglyceride, the LDL-cholesterol that raise comparing embodiment 2 and the embodiment 2; HDL-cholesterol to reducing demonstrates the rising effect, and the result is for suppressing the accumulation of fat in the serum.
What fat content changed in experimental example 4. livers confirms
In order to study among the embodiment 2 the invention combined extracts that obtains depression effect (with comparing in the comparing embodiment 2) for fat content in the fatty liver; According to document (Zlatkis; A and Zak, B.Study of a newcholesterol reagent.Anal.biochem, 29; 143-148,1969) program in has been carried out following test.
After having carried out among the 3-2 similarly step, transmit liver from experimental rat, the saline solution of 2ml is added the liver slice of 1g.To organize with homogenizer and grind, add the CM mixture (chloroform: methanol=2: 1) of 3ml.Repeat above-mentioned steps 3 times, centrifugal suspension is 10 minutes under the speed of 3000rpm.Remove chloroform layer, remove with nitrogen and desolvate.Add and contain the Triton X-100 of chloroform in case solution stopping body stench is removed remaining chloroform with nitrogen.Use BT2000+ device (SEAC Co.) to measure T-CHOL and triglyceride in the serum.
The result of total cholesterol level
Shown in figure 14, (139.75mg/dl) compares with untreated normal group, and the blood total cholesterol level of the matched group of handling with 1% cholesterol and 35% ethanol increases to 2 times (308.43mg/dl); Yet, demonstrate remarkable reduction effect with the group of the extract-treated of preparation among comparing embodiment 2 and the embodiment 2 for the total cholesterol level that raises, wherein, HF2, HF3 and HF4 processed group (HF2:189.87mg/dl; HF3:185.54mg/dl; HF4:169.85mg/dl) demonstrate for the strong reduction effect (seeing Figure 14) of total cholesterol level that raises.
The result of total triglyceride levels
Shown in figure 15, (63.6mg/dl) compares with untreated normal group, and the total triglyceride levels of blood of the matched group of handling with 1% cholesterol and 35% ethanol increases more than 2 times (173.2mg/dl); Yet, demonstrate remarkable reduction effect with the group of the extract-treated of preparation among comparing embodiment 2 and the embodiment 2 for the total triglyceride levels that raises, similar with the result among Figure 14; Wherein, HF2, HF3 and HF4 processed group (HF2:165.5mg/dl; HF3:158.1mg/dl; HF4:143.0mg/dl) demonstrate for the strong reduction effect (seeing Figure 15) of blood triglyceride level that raises.
Therefore confirm: the extract of preparation demonstrates strong reduction effect for the blood cholesterol levels and the triglyceride that raise among comparing embodiment 2 and the embodiment 2.
What experimental example 5. liver organizations changed confirms
In order to study among the embodiment 2 the invention combined extracts (HF2, HF3 and HF4) that obtains effect (with comparing in the comparing embodiment 2) for the liver organization morphological change; Program according in the document (Hematoxylin and Eosin (H&E) staining, http://www.protocol-online.org) has been carried out following experiment.
After having carried out among the 3-2 similarly step, transmit liver from experimental rat, with liver organization with 10% formalin fixed, through H&E method dyeing (Hematoxylin and Eosin staining, http://www.protocol-online.org).
The result of liver morphological change
Shown in figure 16, with untreated compared with normal, the matched group of handling with 1% cholesterol and 35% ethanol demonstrates fat drop (closing on blood vessel) that number increases and abnormal morphology of stem cell shape; Yet with regard to the general alignment of fat drop number and liver organization, HF4 processed group and normal group similar (seeing Figure 16).
Therefore confirm: with HF2, HF3 and HF4 particularly the group handled of HF4 demonstrate strong depression effect for the liver organization morphological change that alcoholic fatty liver causes.
The variation of experimental example 6.HMG-HMG-CoA gene expression
There is report to point out that HMG-CoA (3-hydroxyl-methyl glutaryl-coenzyme A) reductase has important function in the synthetic and approach that dissociates of cholesterol regulating; The number of enzyme raises owing to taking in ethanol, and the cholesterol that causes raising synthesizes.Therefore; In order to study among the embodiment 2 effect of the change that the invention combined extracts (HF2, HF3 and HF4) that obtains expresses for the HMG-CoA-reductase gene; According to document (Gene C.N; ReedC.H.Selective compensatory induction of hepatic HMG-CoA reductase in response toinhibition of cholesterol absorption.Exp.Biol.Mes.231:559-569,2006) program in has been carried out following experiment.
After having carried out among the 3-2 similarly step, transmit liver from experimental rat, (Gibco, BRL USA) separate RNA in the liver organization to use Trizole reagent.Use M-MLV reverse transcriptase (Gibco; BRL; USA) with the synthetic cDNA of the RNA that extracts, use primer (Seq.#1 (F): TGA GGG AAC CCT GAC ACT TA, Seq.#2 (R): CTT CAA ATT TTGGGC ACT CA) carry out RT-PCR to the HMG-CoA-reductase gene.
The result of HMG-CoA gene expression
Shown in figure 17, compare with untreated normal group (0.805), demonstrate the HMG-CoA gene expression (1.852) of rising with the matched group of 1% cholesterol and the processing of 35% ethanol; Yet compare with matched group, the group of handling with HF2, HF3 and HF4 demonstrates the about 1.5 times gene expression dose (HF2:1.633 of reduction; HF3:1.290; HF4:1.224).
Therefore confirm: with HF2, HF3 and HF4 particularly the cholesterol production that causes for alcoholic fatty liver of the group handled of HF4 reduce and demonstrate strong depression effect (seeing Figure 17).
The assessment of experimental example 7. acute toxicities
In order to measure the toxicity of invention extract, on rat, carried out acute toxic test.15 male and female sd inbred rats are divided into 3 groups, use the invention extract of 3 kinds of dosage to per 5 rats, promptly 1g/kg, 2g/kg and 5g/kg continue 14 days, with the water treatment matched group.Observe 4 all toxic symptoms, for example body weight change, serological analysis and histology's test.
As result of experiment, the rat that imposes the invention extract does not have dead example; There is not improper weight increase of significance and histology test etc.Consistent with these results, confirm that the invention extract is safe.
Below will describe compound method and various excipient, but the invention is not restricted to these.The example of representational preparation is below described.
The preparation of injection
HF4 100mg
Sodium pyrosulfite 3.0mg
Methyl hydroxybenzoate 0.8mg
Propylparaben 0.1mg
Distilled water optimal injection dosage
Active component dissolved prepare injection, control pH injects 2ml reagent bottle (ample) with all compositions then to about 7.5, carries out disinfection through conventional injection preparation.
The preparation of powder
HF3 500mg
Corn starch 100mg
Lactose 100mg
Muscovitum 10mg
Prepare powder through above composition being mixed and injecting packages sealed.
The preparation of tablet
HF2 200mg
Corn starch 100mg
Lactose 100mg
The magnesium stearate optimal dose
Tablet forming prepares tablet through mixing above composition also
Capsular preparation
HF1 100mg
Lactose 50mg
Corn starch 50mg
Muscovitum 2mg
The magnesium stearate optimal dose
The gelatin method for preparing filling gelatin capsule that above composition is mixed and passes through routine.
The preparation of liquid
HF2 1000mg
Sugar 20g
Polysaccharide 20g
Lemon flavouring 20g
With the active component dissolving, then all compositions are injected 1000ml reagent bottle (ample), carry out disinfection through the conventional liq method for preparing.
The preparation of health food
HF3 1000mg
The vitamin mixtures optimal dose
Vitamin A acetate 70mg
Vitamin E 1.0mg
Vitamin B1 0.13mg
Vitamin B2 0.15mg
Vitamin B6 0.5mg
Vitamin B12 0.2mg
Vitamin C 10mg
Biotin 10mg
Nicotiamide 1.7mg
Folic acid 50mg
Calcium pantothenate 0.5mg
The mineral intermixture optimal dose
Ferrous sulfate 1.75mg
Zinc oxide 0.82mg.
Magnesium carbonate 25.3mg
Potassium dihydrogen phosphate 15mg
Calcium hydrogen phosphate 55mg
Potassium citrate 90mg
Calcium carbonate 100mg
Magnesium chloride 24.8mg
Said vitamin and mineral intermixture can change in many ways.Should not be considered as such variation and departed from purport of the present invention and scope.
The preparation of healthy beverage
HF4 1000mg
Citric acid 1000mg
Oligosaccharide 100g
Fructus Pruni concentrate 2g
Taurine 1g
Distilled water 900ml
With the active component dissolving, mix, stirred 1 hour at 85 ℃, filter, then all compositions are injected 1000ml reagent bottle (ample), carry out disinfection through conventional healthy beverage method for preparing.
Therefore the present invention is described, and it is obvious that: the present invention much mode changes.Should not be considered as such variation and departed from purport of the present invention and scope, conspicuous for a person skilled in the art all such changes all are believed to comprise within the scope of following claim.
Industrial applicibility
Combined herbs compositions according to the invention demonstrates strong depression effect for the GOT, GPT, cholesterol, triglyceride, the LDL-cholesterol that raise; And demonstrate strong rising effect, and prevention and treatment liver cirrhosis and fatty liver for the HDL-cholesterol that reduces.
Invention compositions according to the invention is useful in prevention and treatment hepatopathy, can be used as safe and efficient liver protecting property reagent.
The sequence table literal
SEQ?ID?NO.1：TGA?GGG?AAC?CCT?GAC?ACT?TA
SEQ?ID?NO.2：CTT?CAAATT?TTG?GGC?ACT?CA
Sequence table
< 110>Li Zhengzhi
< 120>be used to prevent and treat the compositions that comprises extract of combined herbs of hepatopathy
<130>590452CP
<160>2
<170>PatentIn?version?3.4
<210>1
<211>20
<212>DNA
< 213>artificial sequence
<400>1
tgagggaacc ctgacactta ?20
<210>2
<211>20
<212>DNA
< 213>artificial sequence
<400>2
cttcaaattt?tgggcactca 20
Claims (4)
1. pharmaceutical composition; It comprises the extract of combined herbs of the unique active component of conduct of the dosage that can effectively prevent and treat fatty liver, hepatomegaly, liver abscess or liver cirrhosis; Described combined herbs is made up of Coriolous Dersicolor (Fr.) Quel Coriolus versicolor, Radix Astragali Astragalus membranaceus Bunge, Fructus Schisandrae Chinensis Schisandra chinensis and Herba Artemisiae Scopariae Artemisia capillaris; It is with the ratio mixed based on every kind of medical herbs dry weight w/w%, and ratio is between 1-2: 1-2: 1-2: 1.
2. pharmaceutical composition according to claim 1, wherein said extract is selected from the crude extract that dissolves in distilled water, methanol, ethanol or its mixture; Ethanol insolubility component extract or non-polar solven soluble extract; Said ethanol insolubility component extract prepares through following steps: the mixed solution with the second alcohol and water extracts crude extract with separating alcohol soluble component and ethanol insolubility composition, and collects ethanol insolubility component extract; Said non-polar solven soluble extract prepares through following steps: separate crude extract with hexane, chloroform, dichloromethane or ethyl acetate, and collect said non-polar solven soluble extract.
3. healthy functions food; It comprises the extract of combined herbs of the unique active component of conduct of the dosage that can effectively prevent and improve fatty liver, hepatomegaly, liver abscess or liver cirrhosis; Described combined herbs is made up of Coriolous Dersicolor (Fr.) Quel, the Radix Astragali, Fructus Schisandrae Chinensis and Herba Artemisiae Scopariae; It is with the ratio mixed based on every kind of medical herbs dry weight w/w%, and ratio is between 1-2: 1-2: 1-2: 1, and prevent and improve hepatopathy through the protection hepatocyte.
4. healthy functions food according to claim 3, wherein said extract is selected from the crude extract that dissolves in distilled water, methanol, ethanol or its mixture; Ethanol insolubility component extract or non-polar solven soluble extract; Said ethanol insolubility component extract prepares through following steps: the mixed solution with the second alcohol and water extracts crude extract with separating alcohol soluble component and ethanol insolubility composition, and collects ethanol insolubility component extract; Said non-polar solven soluble extract prepares through following steps: separate crude extract with hexane, chloroform, dichloromethane or ethyl acetate, and collect said non-polar solven soluble extract.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020060130518A KR100864455B1 (en) | 2006-12-20 | 2006-12-20 | A Composition comprising the extract of complex herb improving Liver Cirrhosis, cytotoxicity and liver injury for preventing and treating of liver disease |
| KR1020060130518 | 2006-12-20 | ||
| KR10-2006-0130518 | 2006-12-20 | ||
| KR1020070132451 | 2007-12-17 | ||
| KR10-2007-0132451 | 2007-12-17 | ||
| KR1020070132451A KR100953813B1 (en) | 2007-12-17 | 2007-12-17 | Composition comprising the extract of mixed herb suppressing lipid generation for preventing and treating fatty liver disease |
| PCT/KR2007/006648 WO2008075888A1 (en) | 2006-12-20 | 2007-12-18 | A composition comprising the extract of combined herbs for preventing and treating liver disease |
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| CN101563092A CN101563092A (en) | 2009-10-21 |
| CN101563092B true CN101563092B (en) | 2012-09-05 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107823228B (en) * | 2010-10-06 | 2021-07-20 | 寶佳生物科技有限公司 | Coriolus versicolor extract and preparation method and application thereof |
| CN104547215A (en) * | 2014-11-29 | 2015-04-29 | 张莘蔓 | Traditional Chinese medicine composition containing centella asiatica |
| KR20160142713A (en) | 2015-06-03 | 2016-12-13 | 대구한의대학교산학협력단 | Composition Comprising Artemisiae apiaceae Herba extracts for preventing or treating nonalcoholic fatty liver disease |
| CN104887937A (en) * | 2015-06-06 | 2015-09-09 | 林婉骞 | Medicine used for treating fatty liver |
| KR101786180B1 (en) | 2015-06-23 | 2017-10-17 | 대구한의대학교산학협력단 | Composition comprising Spirodela polyrhiza extracts for preventing or treating nonalcoholic fatty liver disease |
| KR101865360B1 (en) * | 2015-07-15 | 2018-06-07 | 주식회사 유니베라 | Compositions and medical compositions for treatment of and maintaining the health of the liver |
| KR101892381B1 (en) | 2017-01-12 | 2018-08-27 | 대구한의대학교산학협력단 | Composition for preventing or treating liver disease comprising pericarpium zanthoxyli extracts |
| CN107569637A (en) * | 2017-09-01 | 2018-01-12 | 赣州市青衫堂中草药有限公司 | Chinese medicine composition for treating hepatic sclerosis and preparation method and application |
| KR102261920B1 (en) * | 2018-06-05 | 2021-06-07 | 대한민국(농촌진흥청장) | Composition comprising Astragali radix derivatives and Lithospermi radix derivatives for preventing and treating liver injury |
| KR20210007156A (en) | 2019-07-10 | 2021-01-20 | 대구한의대학교산학협력단 | Composition comprising icaritin and quercetin for preventing or treating nonalcoholic fatty liver disease |
| KR102517886B1 (en) * | 2020-10-26 | 2023-04-04 | 주식회사 우제아이엠 | Korean Medicine Composition Comprising Herbal Mixture for Improving Liver Function |
| CN114831234A (en) * | 2022-05-28 | 2022-08-02 | 辛三娃 | Beverage for benefiting gallbladder, lowering blood pressure and reducing blood fat and preparation method thereof |
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| CN1324656A (en) * | 2001-06-06 | 2001-12-05 | 张书东 | Chinese medicine prepn. with immunity strengthening effect |
| CN1446553A (en) * | 2002-03-24 | 2003-10-08 | 邱学良 | Medicine for treating chromic avidity, persistent hepatitis B and its preparation method |
| CN1686441A (en) * | 2005-05-08 | 2005-10-26 | 香港生物科技研究院有限公司 | Chinese medicine capsule used for regulating immunity, its preparation method and use |
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| JP2007095001A (en) * | 2005-09-30 | 2007-04-12 | Noritsu Koki Co Ltd | Print processing system |
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| CN1324656A (en) * | 2001-06-06 | 2001-12-05 | 张书东 | Chinese medicine prepn. with immunity strengthening effect |
| CN1446553A (en) * | 2002-03-24 | 2003-10-08 | 邱学良 | Medicine for treating chromic avidity, persistent hepatitis B and its preparation method |
| CN1686441A (en) * | 2005-05-08 | 2005-10-26 | 香港生物科技研究院有限公司 | Chinese medicine capsule used for regulating immunity, its preparation method and use |
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Also Published As
| Publication number | Publication date |
|---|---|
| KR20080057368A (en) | 2008-06-25 |
| CN101563092A (en) | 2009-10-21 |
| KR100864455B1 (en) | 2008-10-20 |
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