CN108348566A - For treating liver and maintaining composition, method and the pharmaceutical composition of liver health - Google Patents

Abstract

It discloses for treating liver and maintaining the composition and method of liver health comprising the mixture of plant extracts, wherein the plant extracts includes at least one artemisia extract, at least one Aloe gel powder and at least one Schizandra extract.It discloses for treating liver and maintaining the composition and method of liver health, it includes the mixture of plant extracts, the wherein described plant extracts includes at least one artemisia extract rich at least one polymer or biopolymer, at least one Aloe gel powder rich at least one chromone and at least one Schizandra extract rich at least one lignan and organic acid.

Description

For treating liver and maintaining composition, method and the pharmaceutical composition of liver health

This application claims entitled " the Compositions and Methods for submitted on July 15th, 2015 The U.S. Provisional Patent Application Serial Article No. of Liver Health (composition and method that are used for liver health) ": 62192711 And entitled " Compositions, Methods, and the Medical Compositions that on July 12nd, 2016 submits For Treatment of and Maintaining the Health of the Liver are (for treating liver and maintaining liver Composition, method and the pharmaceutical composition of dirty health) " U.S. utility application sequence No.:15208075 priority, they It is jointly owned, and is hereby incorporated by reference in its entirety..

The field of theme

The field of theme is the compound and composition for liver health management, includes the alloisomerism of disclosed compound Body, acceptable salt, tautomer, glucosides and prodrug pharmaceutically or in health care, improve and maintain the composition of liver health And correlation technique.

Background

Liver is the vitals to play a crucial role in the metabolism and removing toxic substances of various endogenous and exogenous harmful substance.It is believed that It has occurred in liver and is chemically reacted more than 500 kinds.Known various xenobiotics or exogenous chemical substance can cause hepatotoxicity, Middle paracetamol (n- acetyl group-para-aminophenol or APAP) and carbon tetrachloride (CCl₄) have commonly used in exploitation simulation The animal model of the human liver pathotype of similar mechanism of action.A series of biological markers from serum or liver homogenate Object has been used for the health status for checking and/or analyzing liver, wherein it is considered as the damage to organ to deviate normal range (NR) Instruction.In these biomarkers, the most commonly used is：ALT (alanine aminotransferase), AST (aspartate transaminase), MDA (malonaldehyde), GSH (glutathione), SOD (superoxide dismutase), c-Jun N- terminal Kinases (JNK), GSH-Px (paddy Guangs Sweet peptide peroxidase), CAT (catalase) and TNF-α (tumor necrosis factor-alpha).By liver function panel (liver panel) such as AST, ALT, total bilirubin, combination and unconjugated bilirubin, bile acid, total protein, albumin, ball egg White and alkaline phosphatase is used as the standard screening methods of liver health.While it is recognized that ALT and AST is non-spy for hepar damnification Anisotropic, but ALT has shown that relative specificity to liver.For example, AST has liver (9000:1) opposite muscle (5200:1) Starting ratio；In contrast, ALT has liver (7600:1) opposite muscle (750:1) starting ratio.Total AST's and ALT Half-life period is respectively 17 ± 5 hours and 47 ± 10 hours.ALT stablizes 3 days at room temperature, stablizes in refrigerator 3 weeks, in whole blood Stablize 24 hours；However, ALT with multigelation rapid degradation.In our study, Serum ALT is used for plant and carries The effect of taking object is screened.

APAP is very safely and effectively anodyne and antipyretic under therapeutic dose.This is U.S.'s acute liver failure Most common reason.The hepatotoxicity of APAP inductions is clinically relevant, is fully studied, can be fast in vivo with single dose Speed induction, and have become the conventional model of the potential Hepatocyte protection of assessment fitoterapia.

Caused by the cell death of APAP inductions is not the single unfortunate event by the critical function of closing cell, on the contrary, It induces the sequence of events being formed by reactive metabolin and caused mitochondria dysfunction, the mitochondrial function barrier Hinder and expanded by JNK approach, eventually leads to non-functional mitochondria and a large amount of DNA degradations, lead to meronecrosis.

APAP toxicity is occurred with extremely complex mechanism of action approach.As determined by previously, the cell of APAP inductions is dead The Cellular Signaling Transduction Mediated mechanism died is the sub-fraction by dosage by P450 enzymes (mainly Cyp 2e1 and 1a2 (Zaher Et al., 1998)) it is metabolized to what n- acetyl group 1,4-benzoquinone imines (NAPQI) was caused.Under normal circumstances, this high activity generation Thanking to object will be detoxified by GSH, cause extensive liver GSH to exhaust (Mitchell et al., 197), this becomes in overdose to pass It is important.Meanwhile more and more NAPQI are reacted with protein sulfhydryl, cause cell protein covalent addition (Jollow etc., 1973).It is interesting that research shows that the gross protein in cell is combined be not as important as the adduct in mitochondria (Tirmenstein and Nelson, 1989;Qiu et al., 2001).Mitochondrial protein combines triggering mitochondria oxidative stress (Jaeschke, 1990) causes Apoptosis signal-regulating kinase 1 (Nakagawa et al., 2008) and c-Jun N-terminals to swash The activation of enzyme (JNK) (Hanawa et al., 2008) and mitochondrial oxidation stress be with the peroxinitrites of mitochondria JNK transpositions The amplification (Saito et al., 2010a) that salt is formed.Extensive oxidative stress finally triggers membrane permeability transformation (MPT) in mitochondria The opening in hole, with film potential collapse (Kon et al., 2004;Masubuchi et al., 2005;Ramachandran et al., 2011a;Loguidice and Boelsterli, 2011), then from albumen between mitochondria release film, such as endonuclease G With apoptosis inducing factor (AIF) (Kon et al., 2004;Bajt et al., 2008).Endonuclease G and AIF are shifted To nucleus and cause DNA fragmentation (Cover et al., 2005;Bajt et al., 2006,2011) and cell finally occurs It is dead.It is exhausted with ATP and the mitochondrial membrane potential collapse of core degradation is the critical event for leading to meronecrosis.Therefore, it is setting When meter is used for the therapy intervention of liver protecting, there are multiple noise spots that can intercept these mechanism.

The chronological event for understanding model pathologic process provides guidance for therapy intervention.Although oxidative stress and nothing Bacterium inflammation plays a significant role in APAP toxicity, but the Pathological Physiology of model is characterized in that sequence of events, is included in 0 And the metabolism activation between 2 hours, the GSH in first 30 minutes exhaust, the intracellular machine of the cell death between 2 and 12 hours System, the inflammatory reaction in 6-24 hours time ranges, and after APAP toxicity in 24-72 hours time ranges again Raw (Jaeschke et al., 2012a).

As described above, APAP overdoses can cause with protein adduct formed (Davern et al., 2006; James Et al., 2009), injury of mitochondria and the core DNA fragmentation (McGill et al., 2012a) of cell death is caused to be characterized The major Liver toxicity of the mankind.Therefore, it when test is for liver-protective plant extracts, needs similar using that may have The animal model of pathophysiological features.Therefore, for experiment in vivo, mouse is preferred model, because in mechanism and dosage In terms of dependence, damage is closely similar with human pathologies' physiology.In fact, some think APAP livers between mouse and people The main significant difference of toxicity is the toxicity of the relatively delay of the mankind, after contact the 24-48 hours peaks display ALT, and compares it The lower peaks mouse ALT were at 6-12 hours (Larson, 2007).This species diversity can be partly not construed as because of the two species Between absorption difference.On the contrary, although rat is usually used in natural products detection, but since most of rat strains are to APAP poison Property it is substantially insensitive (Mitchell et al., 1973;McGill et al., 2012b), thus rat is the model of difference.Even if When the high dose of >=1g/kg, APAP will not also cause relevant hepar damnification (Jaeschke et al., 2013) substantially.Although can To measure GSH exhaustion and protein adduct, but compared with mouse, the adduct of relatively low amount seems insufficient in rat liver mitochondria With cause enough mitochondria dysfunctions and subsequent amplification event with cause necrosis (McGill et al., 2012b).These basic differences between the two species reflect in the evaluation process of fitoterapia.For example, In rat studies, compared with baseline, the APAP dosage of 3g/kg causes plasma A LT levels to increase to about 3 times, and fitoterapia This medium hepar damnification is set to alleviate 33% (Ajith et al., 2007).Any histological change in the rat model is all It very little and is difficult to detect.On the other hand, in mice study, after 300mg/kg APAP dosage, ALT increases>60 times of baseline, 75% (Wan et al., 2012) is reduced by fitoterapia.It is easily observed that the histological change caused by APAP toxicity and drug Protective effect.

CCl₄It is the halogenated alkane industrial chemical that limitation uses, is well-known hepatotoxin, it is big is widely used in induction Measure the acute toxic hepar damnification of laboratory animal.The mankind have contacted occupational environment and neutralize (such as to get dirty from environmental pollution The drinking water of dye) CCl₄.Nevertheless, the chemicals currently still provides important purposes as model compound, to explain The mechanism of action of bright hepatotoxicity effect, such as steatosis, fibrosis, hepatocyte death and carcinogenicity (Slater 1981; Renner H. 1985; Reynolds 1963).It is considered as one of the chemical induction hepatotoxicity animal model of classics, It is mainly related with the formation of free radical and lipid peroxidation.

As APAP, CCl₄Toxicity is by predominantly (CYP) 2E1, CYP2B1 or CYP2B2 (Nelson and Harrison, 1987) Cytochrome P450 causes, and generates reactive metabolin trichloromethyl free radical (CCl₃), it can Cause lipid peroxidation and eventually lead to active oxygen species (ROS) it is excessive generation with hepatocellular injury (Poyer et al., 1980;Albano et al., 1982).In this process, these free radicals can be with cellular elements (nucleic acid, protein and fat Matter) it combines, damage crucial cell processes, such as lipid-metabolism is possible the result is that steatosis (steatosis) and to this The coup injury (Weddle et al., 1976) of a little macromoleculars.These free radicals can also react to form trichloromethyl peroxide with oxygen Free radical CCl₃OO-, this is a kind of high activity species.Once generating, it will start the chain reaction of lipid peroxidation, to Attack and destruction polyunsaturated fatty acid, polyunsaturated fatty acid especially related with phosphatide.This influences mitochondria, endoplasmic reticulum With the permeability of plasma membrane, lead to the forfeiture of cell calcium chelating and homeostasis, this may significantly contribute to subsequent cellular damage. This respect, antioxidant and free radical scavenger have been used for studying CCl₄The mechanism of toxicity and pass through destroy lipid peroxidation Chain reaction protect the liver cell from CCl₄The damage (Cheeseman et al., 1987) of induction.On a molecular scale, CCl₄In active cell TNF-α (Czaja et al., 1995), nitric oxide (NO) (Chamulitrat et al., 1994, 1995) with transforming growth factor (TGF) (Luckey et al., 2001), which shows is primarily directed toward destruction or fibre by cell Dimensionization.These show to have the plant extracts of anti-inflammatory activity may have potential liver protecting application.Although large dosage of CCl₄Acute give lead to serious necrosis, but usually induce liver fibrosis using chronic give of relatively low-dose.

Oxidative stress is that free radical generates and body passes through and the endogenous antioxidant defense network of various reduction and chelating The imbalance between the capability of its illeffects is offset or is neutralized in interaction.It is fitted when body Antioxidative Defense System lacks When adjusting when, the accumulation of active oxygen species will lead to the activation of the Cellular Signaling Transduction Mediated approach of stress sensitive, to promote Lead to the cellular damage of necrosis.Although entire body of the damage effect of oxidative stress as system, when it be related to it is important When such as liver (main removing toxic substances occurs in liver for organ to remove and be metabolized harmful toxin such as alcohol), and this influence becomes It obtains more harmful.Therefore, liver easily damages caused by by alcohol, because alcohol and its major metabolite acetaldehyde generate active oxygen object Class (ROS) and hydroxyl radical free radical (OH), to change liver Antioxidative Defense System.Due to alcohol exposure repeatedly and caused by wine Most common pathological condition is observed in the relevant liver diseases of essence, such as fatty liver, hepatitis, fibrosis and hardening.With cell Lipid, protein and DNA aoxidize these related results and are confirmed in kinds of experiments animal (Wu and Cederbaum, 2003).Herein, we used the most common animal model with actual clinical meaning, such as APAP, And confirm classical CCl₄The discovery of the hepatotoxicity model of induction.Regardless of for induced hepatotoxicity chemical reagent, APAP and CCl₄The committed step of oxidative stress caused by all shared active oxygen species generated by excessive intermediate metabolites of model, Lead to protein oxidation, lipid peroxidation and DNA damage.

For this purpose, developing, generating and utilizing composition, the pharmaceutical composition for being intended to treatment liver and maintenance liver health To be desirable with correlation technique.Ideal compound, pharmaceutical composition and composition will be sufficient to achieve treatment, including with Lower any one or more：(1) damage of hepatocyte of mammal is treated or prevented；(2) promote liver health；(3) protection is fed The removing toxic substances of newborn animal and anti-oxidant liver enzyme；(4) increase the liver detoxification ability of mammal；(5) mammal is treated or prevented Liver diseases；(6) mitigate the inflammation of mammalian liver；(7) improve liver more new function.Ideal compound and combination Object can derive from or comprising at least one plant extracts, and wherein plant extracts can be enriched with or not be enriched with.As originally opening A part for hair, using commonly using and acceptable model carrys out the compound of test oracle and composition would be desirable.By blocking The main points cut in liver degradation mechanism and to study those results come the therapy intervention that reliably designs liver health be also in accordance with needing It wants.

The general introduction of theme

It discloses for treating liver and maintaining the composition and method of liver health comprising the mixture of plant extracts, The wherein described plant extracts include at least one artemisia (Artemisia) extract, at least one Aloe (Aloe) gel Powder and at least one Schizandra (Schizandra) extract.

It discloses for treating liver and maintaining the composition and method of liver health comprising the mixing of plant extracts Object, wherein the plant extracts includes at least one artemisia extract rich at least one polymer or biopolymer, At least one Aloe gel powder rich at least one chromone, and it is at least one rich at least one lignan and organic acid Schizandra extract.

It also discloses that and maintains liver function for mammal, hepatocellular injury is made to minimize, promote healthy liver, protect liver Dirty anti-oxidant integrality, neutralizes a toxin, and reduces the Free Radical for influencing liver health, and Scavenger of ROS species reduce oxidation Stress, it prevents toxic metabolite from being formed, improves liver detoxification ability and/or function, clear liver, restore liver structure, protect liver cell With Ozoban, liver blood flowing and cycle are helped, supports liver function, enhanced and liver of releiving, calmed down and take a tonic or nourishing food to build up one's health liver, alleviate Liver pain removes harmful chemical substance and organism, supports the metabolic process of liver, mitigates liver discomfort, mitigates fat Liver improves liver detoxification ability, reduces liver enzyme, provides native oxidant, increases SOD, increases GSH, reduces liver cell peroxidating, Fatty acid accumulation is reduced, the antiinflammatory processes kept fit improve liver immune function, promote liver cell regeneration, improve liver More new function, stimulation bile discharge, and promote healthy bile flow, the pharmaceutical composition and method of liver recovery etc., wherein drug Composition contains expected composition as active ingredient.

Brief description

Fig. 1 displays Artemisia capillaris (Artemisia capillaris) 70% ethanol extract HPLC chromatogram.

Detailed description

In brief, this disclosure relates to which compound and composition for liver health management, including disclosed compound are vertical Body isomers, acceptable salt, tautomer, glucosides and prodrug pharmaceutically or in health care, and improve the phase of liver health Pass method.

Expected compound and composition derive from or comprising at least one plant extracts, and wherein plant extracts can be with Enrichment or not.As a part for this exploitation, using commonly using and acceptable model comes the compound and group of test oracle Close object.In addition, designing the therapy intervention of liver health by intercepting the main points in liver degradation mechanism and studying those results. Expected compound, pharmaceutical composition and composition are enough to realize treatment, including following any one or more：(1) treatment or Prevent the damage of hepatocyte of mammal；(2) promote liver health；(3) removing toxic substances of protection mammal and anti-oxidant liver enzyme； (4) increase the liver detoxification ability of mammal；(5) liver diseases of mammal are treated or prevented；(6) mitigate mammal The inflammation of liver；(7) improve liver more new function.

Specifically, disclosing for treating liver and maintaining composition, the Compounds and methods for of liver health comprising The mixture of plant extracts, wherein the plant extracts includes at least one artemisia extract, at least one Aloe is solidifying Rubber powder end and at least one Schizandra extract.

Furthermore disclosed for treating liver and maintaining composition, the Compounds and methods for of liver health comprising plant The mixture of extract, wherein the plant extracts includes at least one rich at least one polymer or biopolymer Artemisia extract, at least one Aloe gel powder rich at least one chromone and at least one are rich at least one wooden phenol The Schizandra extract of element and organic acid.

It also discloses that and maintains liver function for mammal, hepatocellular injury is made to minimize, promote healthy liver, protect liver Dirty anti-oxidant integrality, neutralizes a toxin, and reduces the Free Radical for influencing liver health, and Scavenger of ROS species reduce oxidation Stress, it prevents toxic metabolite from being formed, improves liver detoxification ability and/or function, clear liver, restore liver structure, protect liver cell With Ozoban, liver blood flowing and cycle are helped, supports liver function, enhanced and liver of releiving, calmed down and take a tonic or nourishing food to build up one's health liver, alleviate Liver pain removes harmful chemical substance and organism, supports the metabolic process of liver, mitigates liver discomfort, mitigates fat Liver improves liver detoxification ability, reduces liver enzyme, provides native oxidant, increases SOD, increases GSH, reduces liver cell peroxidating, Fatty acid accumulation is reduced, the antiinflammatory processes kept fit improve liver immune function, promote liver cell regeneration, improve liver More new function, stimulation bile discharge, and promote healthy bile flow, the pharmaceutical composition and method of liver recovery etc., wherein drug Composition contains expected composition as active ingredient.

Hepar damnification, general fatigue and tired out caused by alcohol are paid close attention to, it is found that compound and extract have enhancing The unique mixture of effect be directed to be repeatedly exposed to oxidative stress it is liver-protective design developed.In history, some are rich in The plant of phenolic compound has been reported related with the antioxidation in biosystem, they are as singlet oxygen and free radical Scavenger so that they be used for herbal medicine.Have effects that understand and the vegetable material pair of safety data it is expected that combination is this Whole liver health will be advantageous.Therefore, APAP and CCl₄Model is used to screen each Plant Extracts.As a result, some Plant extracts only shows the reduction of Serum ALT in a kind of model, but the mark for the primer to be considered Standard is all to show effect in two kinds of models.

In 38 plant materials tested in total, Schisandra chinensis, wormwood artemisia and N931 are only to be shown in two kinds of models The material of its effect.N931 is 200 containing 1-4% Aloesins and 96-99%:1 aloe vera (Aloe vera) internal lobe landing powder The composition of the unique combination of last (inner leaf fell powder) polysaccharide.As disclosed herein, it is contemplated that composition It generally comprises solidifying from the artemisia extract rich in one or more biopolymers, the Aloe rich in one or more chromones The mixture of the plant extracts of rubber powder end and the Schizandra extract rich in one or more lignans and organic acid.

Inhibition level observed by these materials between models and is differed.For example, although Schizandra carries Object is taken to seem to show higher protective effect (up to 48.9% when dosage is 500mg/kg) to hepar damnification caused by APAP, but Under same dose, extract is in CCl₄22.8% inhibiting effect is only shown in the hepatotoxicity model of induction.On the other hand, In CCl₄In the hepatotoxicity model of induction, artemisia extract such as Artemisia capillaris shows Serum ALT water when dosage is 400mg/kg Pancake low 48.0%；In contrast, compared with intermedium control, under the dosage level, in the liver damage model of APAP inductions In the inhibition observed be only 24.0%.These the strong distinct performances observed in independent model in view of each plant, will These plant extracts combine to be enhanced all to obtain the idea of better result in two kinds of models.N931 is in two kinds of moulds Appropriate liver protecting activities are all shown in type.As described above, considerable research is confirmed with different degrees of liver The Schisandra chinensis of protective capability, the antioxidant activity of wormwood artemisia and N931.However, never with specific ratio combine one before them It rises, to generate expected and disclosed composition, including SAL, is generally understood as the unique combination of Schisandra chinensis, wormwood artemisia and N931.

One interesting to be the discovery that, when Schisandra chinensis with the dosage of 400mg/kg with 4:1、2:1、1:1、1:2 and 1:4 ratio When being blended with Artemisia capillaris, 2 only in APAP models:1 (Schisandra chinensis is twice of Artemisia capillaris) and CCL₄1 in model:2 (mattresses Old wormwood artemisia is twice of Schisandra chinensis) show respectively compared with the intermedium control of damage 48.0% and 40.6% Serum ALT levels It reduces.They all do not show expected effect with single ratio in two kinds of models, demonstrate the need for the third component to complete The composition.N931 is considered as the component, because it all shows medium inhibition in two kinds of models.In both guides The liver protecting activities that N931 shows similar degree in two kinds of models are added in blend：That is it is respectively in two kinds of models 52.5% and 46.3%, this is considered as the additional benefit brought due to the third of composition or compound component.Work as test When the advantages of preparing these three vegetable materials, observed from the combination of these three vegetable materials beyond the unexpected of prediction result Synergistic effect, the prediction result is arrived with 400mg/kg observed at doses under given ratio based on its each ingredient The simple adduction of effect.

In fact, without ingredient show with the expected compound or composition comprising Schisandra chinensis, wormwood artemisia and N931 shown by Same degree liver protecting activities.In addition, including AST, ALT, bile acid, total protein, total bilirubin, in conjunction with bilirubin, The data of the liver function panel of albumin and total protein are shown, compared with the control-animal with damage of medium treatment, Desired composition includes liver protecting activities.As the data from liver homogenate reflect, include the contemplated composition of SAL Also the liver glutathione for increasing related consumption with Liver Superoxide Dismutase Activity activity is supplemented.4S:8A:3L's is expected With unique ratio liver is demonstrated in adjusting relevant several animal models with several oxidative stress specific biomarkers Dirty protection activity.

As disclosed herein, artemisia extract and Schizandra extract can be with 4:1 to 1:4 weight ratio is blended. In some expected embodiments, Aloe gel powder can be further with the weight percent of about 5% to about 50% and wormwood artemisia Belong to and the mixture of Schizandra extract is blended.In other expected embodiments, artemisia, Schizandra and Aloe leaf The mixture of gel powder can be to be respectively 8:4:3 ratio provides.

Schizandra extract can be used as the expection component or ingredient of a part for target compound or composition.The five tastes Son, which belongs to extract, to be obtained from any suitable source, including Schisandra chinensis (Schisandra chinensis), Schisandra elongate, Schisandra glabra, Kingsoft Schisandra chinensis (Schisandra glaucescens), Schisandra henryi Clarke (Schisandra henryi), Schisandra incarnate, narrow leaf Schisandra chinensis (Schisandra ), lancifolia nepal magnoliavine fruit (Schisandra neglecta), Schisandra nigra close stamen Schisandra chinensis (Schisandra propinqua), nerville Schisandra chinensis (Schisandra pubescens), two color Schisandra chinensis (Schisandra repanda), Schisandra sphnanthera (Schisandra rubriflora), Schisandra Rubrifolia, Schisandra sinensis, ball stamen Schisandra chinensis (Schisandra sphaerandra), Central China five tastes Sub (Schisandra sphenanthera), pubescence Schisandra chinensis (Schisandra tomentella), tumor branch Schisandra chinensis (Schisandra tuberculata), hair leaf Schisandra chinensis (Schisandra vestita), Schisandra viridis (Schisandra viridis), Heqing Schisandra chinensis (Schisandra wilsoniana) or combinations thereof.

As used herein envisaged, Schizandra extract can be rich in one or more lignans and organic acid.It is expected that from five The lignan isolated in taste category extract is schizandrin, deoxidation schizandrin, wuweizisu B, the puppet-γ-five tastes Sub- element, wuweizisu B, schisandrin C, isoschizandrin, Pregomisin, eoschizandrin, schisandrol, Wuweizi alcohol A, wuweizi alcohol B, Schisantherin A, B, C, D, E, rubschisantherin, schisanhenol acetate (Schisanhenol acetdte), schisanhenol B, schisanhenol, gomisin A, B, C, D, E, F, G, H, J, N, O, R, S, T, U, table Gomisin O, Radix Angelicae Sinensis acyl gomisin H, O, Q, T, igloylgomisin H, P, Radix Angelicae Sinensis The different Gomisin O of acyl, benzoyl-gomisin H, O, P, Q, different Ge meter Xin of benzoyl-or combinations thereof.It is expected that from the five tastes The organic acid that son belongs to extract separation includes malic acid, citric acid, shikimic acid or combinations thereof.

Artemisia extract can be used as the expection component or ingredient of a part for target compound or composition.Artemisia is extracted Object can be obtained from any suitable source, including both A. absinthium (Artemisia absinthium), south wood wormwood artemisia (Artemisia abrotanum L.), African wormwood artemisia (Artemisia afra), artemisia annua (Artemisia annua L), Set wormwood artemisia (Artemisia arborescens), Asia wormwood artemisia (Artemisia asiatica), wilderness wormwood artemisia (Artemisia ), campestris Artemisia deserti, Artemisia iwayomogi, grey wormwood artemisia (Artemisia ), ludoviciana north Chinese mugwort (Artemisia vulgaris), Artemisia oelandica, stalwart wormwood artemisia (Artemisia Princeps Pamp), white lotus wormwood artemisia (Artemisia sacrorum), artemisia scoparia (Artemisia scoparia), Artemisia stelleriana (Artemisia stelleriana), prairie sagewort (Artemisia frigida Willd), Dillleaf Wormwood (Artemisia Anethoides Mattf.), alkali wormwood artemisia (Artemisia anethifolia Weber.), Artemisia faurier Nakai, wild marjoram (Origanum vulgare), siphonstegia chinensis (Siphenostegia chinensis) or any combination thereof.

As contemplated herein, artemisia extract can be rich in one or more biopolymers.Divide from artemisia extract From expection polymer and any suitable solvent extraction of biopolymer, including water, methanol, ethyl alcohol, alcohol, water mixed solvent Or combinations thereof.In expected embodiment, artemisia extract includes about 0.01% to about 99.9% with greater than about 500g/mol Independent or median MW biopolymer.In some expected embodiments, artemisia extract include about 0.01% to About 99.9% has independent or median MW the biopolymer of greater than about 750g/mol.In other expected embodiments In, artemisia extract includes about 0.01% to about 99.9% with greater than about independent or median MW the biology of 1000g/mol Polymer.

Aloe gel powder is component or ingredient expected from another kind, can be provided by any suitable source, including wood Vertical aloe (Aloe arborescens), aloe barbadensis Miller (Aloe barbadensis), Aloe cremnophila are good Hope angle aloe (Aloe ferox), A.saponaria (Aloe saponaria), aloe vera (Aloe vera), the Chinese aloe aloe (Aloe vera var. chinensis) or combinations thereof.

As contemplated herein, Aloe gel powder can be rich in one or more chromones.Expected chromone include or Selected from Aloesin (aloesin), aloesinol, aloe (aloeresin) A, aloe B, aloe C, aloe D, aloe E or any combination thereof.In expected embodiment, at least one chromone compositions About 0.01% to about 100% one or more chromones can be included.In some expected embodiments, chromone compositions include The Aloesin of about 1% to about 4%, wherein the composition are substantially free of anthraquinone and wherein aloe gel is from selected from Curacao reed The plant of luxuriant growth or aloe vera detaches；And wherein described at least one chromone is from aloe vera or Aloe ferox Miller Middle separation.

Expected compound, pharmaceutical composition and composition may include or additionally comprise or form to protect from least one liver Protect agent.In some embodiments, at least one hepatoprotective can include following or be made up of：Milk Thistle, ginger Huang, radix bupleuri, Radix Glycyrrhizae, Salvia japonica, mulberry, Zhi Ji, hairyvein agrimony, cudrania cochinchinensis, lyceum, citrus, Lee, yellow plum, Korea gim, dandelion, Grape, grape pip, raspberry, camellia, green tea, krill oil, yeast, soybean plant powder or plant extracts；Separation and richness Silymarin, flavonoids, phosphatide, thios, pycnogenol, gelatin, soybean lecithin, the pancreatin of collection；Natural or synthetic N- acetyl Cysteine, taurine, riboflavin, niacin, pyridoxol, folic acid, carrotene, vitamin A, vitamin B2, B6, B16, dimension life Plain C, vitamin E, glutathione, branched-chain amino acid, selenium, copper, zinc, manganese, Co-Q10, L-arginine, L-Glutamine, phosphatide Phatidylcholine etc. and/or a combination thereof.

It is also contemplated by the interior metabolism product of disclosed compound herein.These products may be by chemical combination for example to be administered Oxidation, reduction, hydrolysis, amidation, esterification of object etc. cause, mainly due to enzymatic processes.Therefore, desired compound is By including giving desired compound or composition to mammal to be enough to generate the method production of the time of its metabolite Those of raw compound.Usually by giving the radiolabeled compound of the disclosure to animal (example with detectable dosage Such as rat, mouse, cavy, dog, cat, pig, sheep, horse, monkey or people), allow enough time for the generation of metabolism, then from urine Its converted product is detached in liquid, blood or other biological samples, to the such product of identification.

As used herein, phrase " stable compound " and " rock-steady structure " are used interchangeably, and are used to indicate enough steadily and surely It is detached to useful purity from reaction mixture to be subjected to and is subjected to being configured to the compound of effective therapeutic agent.

As used herein, term " mammal " includes the mankind and domestic and non-domestic animals, and domestic animal is for example tested Room animal or house pet, such as rat, mouse, cavy, cat, dog, pig, ox, sheep, goat, horse, rabbit, primate, it is non- Domestic animal is such as wild animal.

As it is used herein, term " optional " or " optionally " may be used interchangeably, and mean then to describe Element, component, event or situation may occur or may not occur, and include that the element, component, event or situation occurs Situation and situation that they do not occur.It can be substituted or can not for example, " aryl optionally replaced " refers to aryl Substituted-in other words, which includes the aryl of substitution and the aryl without substituent group.

Expected compound, pharmaceutical composition and composition can include or additionally comprise or form from least one pharmacy Acceptable carrier, diluent or excipient in upper or health care.As used herein, phrase is " acceptable pharmaceutically or in health care Carrier, diluent or excipient " includes any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye Material/colorant, flavoring agent, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent or emulsifier, It has been approved as being acceptable for the mankind or domestic animal by food and drug administration.

Expected compound, pharmaceutical composition and composition can include or additionally comprise or form from least one pharmacy Acceptable salt in upper or health care.As used herein, phrase " pharmaceutically or in health care acceptable salt " include acid-addition salts and Base addition salts.

As used herein, phrase " pharmaceutically or in health care acceptable acid-addition salts " refers to the biology for retaining free alkali Those of validity and property salt are not and to be and inorganic acid and organic biologically or other aspects are undesirable Acid formed, inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid etc., organic acid for example acetic acid, 2,2- dichloroacetic acid, oneself two Acid, alginic acid, ascorbic acid, aspartic acid, benzene sulfonic acid, benzoic acid, 4- acetaminobenzoic acids, camphoric acid, camphor -10- sulphurs Acid, capric acid, caproic acid, octanoic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecyl sulphate, ethane -1,2- disulfonic acid, second sulphur Acid, 2- ethylenehydrinsulfonic acids, formic acid, fumaric acid, galactonic acid, gentianic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, Glutaric acid, 2- oxos-glutaric acid, phosphoglycerol, glycolic, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, Malic acid, malonic acid, mandelic acid, methanesulfonic acid, glactaric acid, naphthalene -1,5- disulfonic acid, -2 sulfonic acid of naphthalene, 1- hydroxy-2-naphthoic acids, niacin, Oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-ASA, the last of the ten Heavenly stems Diacid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-methyl benzenesulfonic acid, trifluoroacetic acid, undecenoic acid etc..

As used herein, phrase " pharmaceutically or in health care acceptable base addition salts " refers to the biology for retaining free acid Those of validity and property salt are not biologically or other aspects are undesirable.These salt to free acid by adding Inorganic base or organic base is added to prepare.Salt from inorganic base includes sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminium salt Deng.In certain embodiments, inorganic salts are ammonium salt, sodium salt, sylvite, calcium salt or magnesium salts.Salt from organic base include with Under salt：Primary amine, secondary amine and tertiary amine include the substitution amine of naturally occurring substitution amine, cyclammonium and deacidite, such as Ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropyl amine (TPA), diethanol amine, ethanol amine, dimethylethanolamine, 2- dimethylaminos Base ethyl alcohol, dicyclohexyl amine, lysine, arginine, histidine, procaine, breathes out amine, choline, beet at 2- DEAE diethylaminoethanols Alkali, phenylethylbenzylamine, benzyl star, ethylenediamine, aminoglucose, methylglucosamine, theobromine, triethanolamine, tromethamine, purine, piperazine, Piperidines, N-ethylpiperidine, polyamino resin etc..Particularly useful organic base includes isopropylamine, diethylamine, ethanol amine, trimethylamine, two Cyclohexylamine, choline or caffeine.

Usually crystallization generates the solvate of desired compound or including desired compound.As used herein, Term " solvate " refers to comprising expected compound, one or more molecules of pharmaceutical composition or composition and one Or the aggregation of multiple solvent molecules.Solvent can be water, and solvate can be hydrate in this case.Alternatively, molten Agent can be organic solvent.Therefore, desired compound, pharmaceutical composition or composition can be used as hydrate presence, including Monohydrate, dihydrate, semihydrate, times semihydrate, trihydrate, tetrahydrate etc. and corresponding solvation shape Formula.Desired compound, pharmaceutical composition or composition can be true solvate, and in other cases, it is contemplated that change The mixture of external water either water and some adventitious solvents can only be retained by closing object, pharmaceutical composition or composition.

" pharmaceutical composition " or " health composition " refer to desired compound, pharmaceutical composition or composition and this The preparation for the medium for bioactive compound to be delivered to mammal (such as people) that field usually receives.For example, can Expected medical compounds, pharmaceutical composition or composition to be configured to or be used as separate composition, or as prescription medicine, non- Prescription (OTC) drug, autonomic drug, herbal medicine, homeopathic drug or any other form for being examined by government organs and being ratified Component in health product.Exemplary and expected health composition can be configured to or be used as separate composition or conduct Food, novel foodstuff, functional food, beverage, stick (bar), flavorant, food additive, medical foods, dietary supplements Or the health care in herbal products or biological active component.The medium that this field usually receives includes all pharmacy for this field Acceptable carrier, diluent or excipient in upper or health care.

As used herein, phrase " being rich in " refers to one or more activations that plant extracts or other prepared products have The institute found in vegetable material or other sources or other prepared products before closing the extraction of the amount or activity and the weight of object The amount or active compare for stating one or more reactive compounds increase at least about 2 times until at most about 1000 times.In certain realities Apply in scheme, the vegetable material or the weight of other sources or other prepared products before extraction can be dry weight, weight in wet base or its Combination.

As used herein, " main active " or " main active component " refers in plant extracts or other prepared products One or more active expecting compounds that are middle discovery or being enriched in plant extracts or other prepared products, can generate At least one bioactivity.In certain embodiments, the main active of extract-enriched will be rich in the extract The one or more reactive compounds contained.In general, compared with other extract components, one or more main active components will be straight Connect or assign indirectly one or more measurable bioactivity or effect of most of (being more than 50%).In certain implementations Can be less component (for example, contained in extract according to the main active of extract weight percentage in scheme Component less than about 50%, 25%, 20%, 15%, 10%, 5% or 1%), but still most of required bioactivity is provided.It is any to include The contemplated composition of main active can also contain secondary active constituent, may or may not contribute to enrichment compositions Drug or health active, but do not reach the level of main active component, and only secondary active constituent is not being lived mainly May not be effective in the case of property ingredient.

As used herein, phrase " effective quantity " or " therapeutically effective amount " refer to desired compound, pharmaceutical composition or The amount of composition, when giving mammal such as people, the amount is enough to realize treatment, including following any one or more： (1) damage of hepatocyte of mammal is treated or prevented；(2) promote liver health；(3) removing toxic substances of protection mammal and antioxygen Change liver enzyme；(4) increase the liver detoxification ability of mammal；(5) liver diseases of mammal are treated or prevented；(6) mitigate The inflammation of mammalian liver；(7) improve liver more new function.Constitute expecting compound, the medicine group of " therapeutically effective amount " Close the amount of object or composition by according to compound, the illness treated and its severity, give mode, duration for the treatment of or Weight and the age for the treatment of object and change, but can by those skilled in the art according to the knowledge of their own and this It discloses to determine.

" replenishers " used herein refer to improving, promoting, supporting, increasing, adjusting, managing, controlling, maintaining, optimizing, repairing It adorns, reduce, inhibit or prevents and native state or the relevant particular condition of bioprocess, the product of structure or function, compound And/or composition (be not used in diagnosis, treatment, mitigation, healing or prevent disease).In certain embodiments, replenishers are Dietary supplements.For example, for disease related with liver health, dietary supplements can be used for mammal and maintain liver function Can, hepatocellular injury, sanatory liver are reduced to the maximum extent, and liver-protective anti-oxidant integrality neutralizes a toxin, subtracts The effect of the free radical of liver health is influenced less, Scavenger of ROS species reduce oxidative stress, prevent the formation of toxic metabolic, Improve liver detoxification ability and/or function, clear liver, restore liver structure, protection liver cell with Ozoban, help liver blood flow and Cycle supports liver function, strengthens and liver of releiving that calm and tonic liver alleviates liver pain, remove harmful chemical with Organism supports the metabolic process of liver, mitigates liver discomfort, mitigates fatty liver, improve liver detoxification ability, reduces liver Enzyme provides native oxidant, increases SOD, increases GSH, reduces liver cell peroxidating, reduces fatty acid accumulation, maintains health Antiinflammatory processes improve liver immune function, promote liver cell regeneration, improve liver more new function, and stimulation bile discharges, promotes The bile flow of health, liver recovery etc..In certain embodiments, dietary supplements be the diet of special category, food or The two, and not drug.

Term " treatment " or " treatment " or " improvement " may be used interchangeably, and refer to closing to suffering from or suspecting to suffer from The disease or illness of the concern of the disease of note or the mammal (such as people) of illness carry out therapeutic treatment or prevention/prevent Property treatment, and include：(i) prevent that disease or illness occur in mammal, especially when this mammal is susceptible to suffer from the disease Disease but when being not yet diagnosed to be with the illness；(ii) inhibit disease or illness, that is, prevent its development；(iii) alleviate disease or disease Disease causes disease or illness to subside；Or (iv) mitigates in the case where not solving potential disease or illness by disease or illness Caused symptom (such as relieving pain, reduce inflammation, reduce the forfeiture of detoxification ability).

As used herein, term " disease " and " illness " may be used interchangeably, or can be different, and difference exists May not have known causative factor (therefore the cause of disease obtains not yet) in the specific state of an illness or illness, therefore not yet be considered It is disease, and is only considered undesirable illness or syndrome, wherein clinician has determined that the symptom of similar specific group. In certain embodiments, desired compound, pharmaceutical composition, composition and method are for treating such as hepatitis, alcohol Hepatopathy, hardening or both.

As used herein, " statistical significance " refers to examining the 0.050 or smaller p value calculated using Students t, And indicate that particular event or measurement result are unlikely to be occurrent.

Chemical name agreement used herein and any structure chart are the modifications of I.U.P.A.C. naming systems, are used 11.0 software naming program of 9.07 software programs of ACD/Name Version or ChemDraw Ultra Version (CambridgeSoft), the compound of the wherein disclosure is named as central core structure, such as imidazopyridine herein The derivative of structure.For complicated chemical title used herein, substituent group is named before the group of its connection.For example, Cyclopropylethyl includes the ethyl backbone with cyclopropyl substituent.

In certain embodiments, it is contemplated that compound and composition (such as drug, health care) a certain amount of can give It gives, the amount is enough to promote liver health；Improve liver health；Keep liver health；Treatment or management liver health；Support liver Dirty health；Support normal and comfort standard liver detoxification function；Improve the free radical scavenging ability of liver；It reduces by chemistry The damage of harmful free radicals derived from product, drug, metabolin and biotoxin；Protection influence liver health enzyme, prevent due to Hepatitis B/infection with hepatitis C virus, drink, metabolic disorder, nonalcoholic fatty liver disease (NAFLD), non-alcoholic fat Liver during fat hepatitis (NASH), alcohol hepatopathy, hepatic encephalopathy, liver fibroproliferative disorders (liver fibrosis), anoxia _ reoxygenation Cellular damage or any combination thereof caused by eremacausis caused by hepar damnification stress；Or any other correlation as described herein Indication, and usually there is acceptable toxicity to patient.

In certain other embodiments, expected compound and composition (such as drug can be given with enough amounts , health care) to treat liver disorders or disease, including virus hepatitis, alcoholic hepatitis, oneself immunity hepatitis, alcohol Hepatopathy, fatty liver, steatosis, steatohepatitis, non-alcoholic fatty liver disease, drug-induced liver diseases, hardening are fine Dimensionization, hepatic failure, drug-induced hepatic failure, metabolic syndrome, hepatocellular carcinoma, cholangiocarcinoma, primary biliary cirrhosis, hair Canals of Hering, gilbert spy's syndrome, jaundice or any other hepatotoxicity correlation indication or combinations thereof, and usually have to patient There is acceptable toxicity.

Desired compound, pharmaceutical composition or composition or its acceptable salt is in a pure form pharmaceutically or in health care Or giving in suitable drug or health composition can be by any receiving of the drug for providing similar applications Pattern is given to carry out.Expected drug or health composition can by by desired compound with it is suitable pharmaceutically or In health care prepared by acceptable carrier, diluent or excipient composition, and can be configured to solid, semisolid, liquid or The preparation of gas form, for example, tablet, capsule, powder, granule, ointment, solution, suppository, injection, inhalant, Gelling agent, microspheres agent and aerosol.The classical pathway for giving such drug or health composition includes oral, local, transdermal, inhales Enter, parenteral, sublingual, oral cavity, rectum, vagina or intranasal.

As used herein, term " parenteral " includes hypodermic injection, intravenous, intramuscular, breastbone inner injection or infusion techniques. Expected drug or health composition are formulated such that active constituent wherein included after composition gives patient Shi Huo Soon it is bioavailable.In some embodiments, desired composition and compound can be designed or be configured to They are discharged when being selected after giving.

In certain embodiments, desired composition given in the form of one or more dosage units subject or Patient, wherein such as tablet can be single dosage unit, and the container of the expecting compound of aerosol form can accommodate it is more A dosage unit.The practical methods for preparing this dosage form are known to those skilled in the art or will be apparent 's；For example, with reference to Remington: The Science and Practice of Pharmacy, 20th Edition (Philadelphia College of Pharmacy and Science, 2000).According to the introduction of present disclosure, wait for The contemplated composition given under any circumstance all by containing the expecting compound of therapeutically effective amount or its pharmaceutically or in health care Acceptable salt, disease or illness for treating concern.

Expected drug or health composition can be solid or liquid forms.In one aspect, carrier is granular, So that composition is for example in tablet or powder type.Carrier can be liquid, and wherein composition is such as oral syrup, injectable Liquid or aerosol can be used for for example sucking and give.

When being intended for oral give, drug or health composition are solid or liquid form, wherein semisolid, half liquid Body, suspension and gel form are included in it is recognized herein that being in the form of solid or liquid.

As for the oral solid composite given, drug or health composition can be configured to powder, granule, pressure Tablet, pill, capsule, chewing gum, wafer, stick or similar type.This solid composite will usually contain a kind of or more Kind inert diluent or edible carrier.In addition, there can be one or more following substances：Adhesive, such as carboxymethyl are fine Tie up element, ethyl cellulose, cyclodextrin, microcrystalline cellulose, bassora gum or gelatin；Excipient, such as starch, lactose or dextrin；Disintegration Agent, such as alginic acid, sodium alginate, Primojel, cornstarch；Lubricant, such as magnesium stearate or Sterotex；Help stream Agent, such as colloidal silicon dioxide；Sweetener, such as sucrose or saccharin；Flavoring agent, such as peppermint, gaultherolin or orange flavoring；With Colorant.

When drug or health composition are capsule form, such as when gelatine capsule, in addition to materials of the above type, also Liquid-carrier such as polyethylene glycol or oil can be contained.

Expected drug or health composition can be liquid form, such as elixir, syrup, gel, solution, emulsion or mixed Suspension.As two examples, liquid can be used for oral give or delivery by injection.When for oral give, in addition to this Except invention compound, the one kind or more of useful composition also containing sweetener, preservative, dyestuff/colorant and flavoring agent Kind.It is being intended to by injecting in the composition given, is may include surfactant, preservative, wetting agent, dispersant, suspension It is one or more in agent, buffer, stabilizer and isotonic agent.

Desired liquid medicine or health composition, no matter they are solution, suspension or other similar types, can To include one or more following adjuvants：Sterile diluent, such as water for injection, saline solution, such as physiological saline, woods grignard Solution, isotonic sodium chloride can be used as the fixing oil of solvent or suspension media, such as the monoglyceride or diglyceride of synthesis, gather Ethylene glycol, glycerine, propylene glycol or other solvents；Antiseptic, such as benzyl alcohol or methyl p-hydroxybenzoate；Antioxidant, it is such as anti- Bad hematic acid or sodium hydrogensulfite；Chelating agent, such as ethylenediamine tetra-acetic acid；Buffer, such as acetate, citrate or phosphate；With And the reagent of tension is adjusted, such as sodium chloride or glucose.Parenteral administration can be encapsulated in ampoule, disposable syringe or by glass In multiple dose vials made of glass or plastics.Physiological saline is usual useful adjuvant.The drug or health composition of injectable It is sterile.

It should includes a certain amount of pre- to be intended for parenteral or the oral expected liquid medicine given or health composition Phase compound, pharmaceutical composition or composition, to obtain suitable dosage.

Expected drug or health composition can be intended for administering locally to, and in this case, carrier can be appropriate Ground includes solution, lotion, emulsifiable paste, lotion, ointment or gel-type vehicle.For example, the matrix can include one or more of： Vaseline, lanolin, polyethylene glycol, beeswax, the diluent of mineral oil, such as water and alcohol and emulsifier and stabilizer.Thickening Agent can reside in drug or health composition for administering locally to.If be intended for use in it is transdermal give, composition can be with Including transdermal patch or iontophoresis device.

Expected drug or health composition can be intended for rectal administration, such as be given in the form of suppository, will It melts in the rectum and discharges drug.Composition for rectal administration can contain as suitable non-irritating excipient Oleaginous base.This matrix includes lanolin, cocoa butter and polyethylene glycol.

Expected drug or health composition may include the various of the physical form of change solid or liquid dosage unit Material.For example, composition may include the material for forming coating shell around active constituent.Formed coating shell material be typically It is inert, and such as sugar, shellac and other enteric coating agents can be selected from.Alternatively, can gelatine capsule be packed into active constituent In.

The drug or health composition of desired solid or liquid form may include being combined with desired compound To help to deliver the reagent of compound.Can include monoclonal or Anti-TNF-α with the suitable agent that this ability works Body, protein or liposome.

The drug or health composition of desired solid or liquid form may include subtracting short grained size with for example Improve bioavilability.In the case where being with or without excipient, the size of powder, particle, particle, microballoon in composition etc. Can be macroscopical (for example, or size visible to eyes is at least 100 μm), micron-sized (such as can be range from about 100 μm arrive the size of about 100nm), nano level the size of 100nm (for example, it may be no more than) and between them any Size or any combination thereof to improve size and heap density.

Expected drug or health composition can include or form from can be as the dosage unit that aerosol is given.Art Language aerosol is for indicating from the system of colloidal nature to the various systems for the system being made of pressurized package.Can by liquefaction or Compressed gas or the suitable pumping system by distributing active constituent are delivered.The aerosol of disclosure compound can be with list Phase, two-phase or three-phase system delivering are with delivering active ingredients.The delivering of aerosol includes necessary container, activator, valve, Asia Container etc., they can form external member together.Those skilled in the art can determine in the case of no excessively experiment and most close Suitable aerosol.

Expected drug or health composition can be prepared by pharmacy or the well-known method of healthcare field.For example, Be intended to by the drug given of injection or health composition can by desired compound is combined with sterile distilled water with Solution is formed to prepare.Surfactant can be added to promote to be formed homogeneous solution or suspension.Surfactant be with it is pre- The compound noncovalent interaction of phase, to promote the chemical combination of dissolving or even suspension of the compound in aqueous delivery system Object.

Expected compound, composition and pharmaceutical composition or its pharmaceutically or in health care acceptable salt to treat effectively Amount is given, and the therapeutically effective amount will change according to many factors, includes the activity of used particular compound；Compound Metabolic stability and action time length；Age, weight, general health, gender and the diet of patient；The mode given And the time；Excretion rate；Pharmaceutical composition；The severity of specified disease or illness；The treatment received with subject.

Expected compound, composition and pharmaceutical composition or its pharmaceutically or in health care acceptable derivates can also It is given simultaneously with one or more giving for other therapeutic agents, or in one or more other therapeutic agents before or after giving It gives.Such combination treatment include give the single medicine containing expected compound and one or more other activating agents or Health care dosage particles, and give expected compound and each activity with its own separated drug or health care dosage particles Agent.For example, desired compound and another activating agent can be with single oral dosage composition (such as tablet or capsules) Giving patient or each drug together can be given with separated oral dosage formulation.When using separated dosage particles, Desired compound and one or more other activating agents can be given in the substantially the same time, i.e., give simultaneously, or Person gives in separated staggered time, i.e., gives successively；Combination treatment is understood to include all these schemes.

It should be understood that in the present specification, it is described only when such contribution generates stable compound The combination of the substituent group or variable of formula is just allowed.

It will further be appreciated by those skilled in the art that in method described herein, the functional group of midbody compound It may need to be protected by suitable blocking group.This functional group includes hydroxyl, amino, sulfydryl and carboxylic acid.Suitable for hydroxyl Protecting group includes trialkylsilkl or diarylalkyl-silyl (such as t-butyldimethylsilyl, tertiary butyl Diphenylsilyl group or trimethyl silyl), THP trtrahydropyranyl, benzyl etc..The appropriate protection base of amino, amidino groups and guanidine radicals Including tert-butoxycarbonyl, benzyloxycarbonyl etc..Protecting group suitable for sulfydryl includes that (wherein R " is alkyl, aryl to C (O) R " Or aryl alkyl), to methoxy-benzyl, trityl etc..The appropriate protection base of carboxylic acid includes alkyl, aryl or aryl alkyl Ester.Protecting group can be added or be removed according to standard technique well known by persons skilled in the art and as described herein.“Green, T.W. and P.G.M. Wutz, Protective Groups in Organic Synthesis (1999), 3rd Ed., The use of protecting group is described in detail in Wiley ", entire contents are incorporated herein by reference.As those skilled in the art will Understand, protecting group can also be fluoropolymer resin, such as Wang resins, Rink resins or 2- chlorine trityl chloride resins.

Skilled person will also understand that although this protected derivative of desired compound itself may Without pharmacological activity, but they can be given mammal, then be metabolized in vivo to be formed with pharmacological activity Compound.Therefore these derivatives can be described as " prodrug ".All prodrugs of desired compound are included in this public affairs In the range of opening.

In addition, by methods known to those skilled in the art, it, can by being handled with suitable inorganic or organic base or acid By will in the form of free alkali or acid existing for expecting compound be converted into its acceptable salt pharmaceutically or in health care.Desired The salt of compound can be converted into their free alkali or sour form by standard technique.

In some embodiments, desired compound, composition and/or pharmaceutical composition can be from plant origins point From, for example, from embodiment with entire the application it is other place include those of plant detach.For detaching expected extract Suitable plant part with compound include leaf, bark, trunk, trunk barks, stem, stem skin, branch, stem tuber, root, root skin, Bark surface (such as perithelium or polyderm, it may include cork, phellogen, phelloderm), spray, rhizome, Seed, oecium, gynoecium, calyx, stamen, petal, sepal, carpel (gynoecium), is spent fruit.Expected plant Object extract is originated from least one plant part selected from the following：Stem, stem skin, trunk, trunk barks, branch, stem tuber, root, root Skin, spray, seed, rhizome, flower and other reproductive organs, leaf, other gas first portions or combinations thereof.In some relevant embodiment party In case, it is contemplated that compound from plant origin separation and synthetic modification to include any substituent group.In this regard, The synthetic modification of the expecting compound detached from plant can use known in the art and completely in the common skill in this field Any amount of technology in the knowledge of art personnel is completed.

Embodiment

Embodiment 1：Animal

The 7-8 week old mesh for being 25-30g from Charles River Laboratories (Wilmington, MA) purchase weight Cultivation mouse.Animal adapts to one week after arrival, is then weighed and is assigned randomly to their own group.By ICR mouse (5/cage) are placed in polypropylene cage, and are identified respectively by the number on its tail portion.Each cage is covered with wire column Lid and filtering top (wire bar lid and filtered top) (Allentown, NJ).Each individually cage is used Cage card identifies that cage card shows project number, test article, dosage level, group and number of animals.Use Harlan The soft corncob beddings of T7087 (soft cob bedding), are replaced weekly at least twice.Arbitrarily provided to animal fresh water and Rodent chows #T2018 (Harlan Teklad, 370W, Kent, WA), and animal is contained in 12 hours brightness In the temperature-controlled chamber (22.2 DEG C) of cycle.All zooperies all in accordance with defined guide carry out, and with experimental animal Nursing is consistent with guide for use.

Embodiment 2：Paracetamol (APAP) or the hepar damnification animal model of carbon tetrachloride (CCL4) induction

The following therapeutic scheme generated and optimization balances, to solve to prevent and intervene：For APAP induction hepatotoxicity model, By the warm saline that is dissolved in of 400mg/kg dosage, (Lot#132908 comes from G-Biosciences, and Lot# 720729 comes from Quality Biological) (it is heated to 60^◦C is simultaneously cooled to environment temperature) in APAP (Lot# MKBQ8028V, come From Sigma) the ICR/CD-1 mouse for giving overnight fast are taken orally with inducing toxic.For CCl₄The hepatotoxicity model of induction, By the CCl of 25 μ l/kg dosage being dissolved in corn oil₄Overnight fast is given in (Lot#SHBD5351V comes from Sigma) peritonaeum ICR/CD-1 mouse with inducing toxic.For both models, in APAP or CCl₄- 48hr before giving ,-r for 24 hours ,- 2hr and induction after+6hr give material.Generally speaking, mouse receives 3 dosage before chemical induction, chemical induction be followed by by 1 dosage.Using 10% Tween-20 (Lot# 0134C141 come from Amresco), (Lot# NH0454, come from 1% CMC ) or carrier intermediates of 1% MC (Lot#SLBK4357V) as all material Spectra.There is no APAP or CCl₄Control Mouse only receives carrier intermediate.Serum ALT is measured in T24 (Phoenix Laboratories, Everett, WA).

Embodiment 3：The preparation of plant extracts

It collects plant and is prepared based on the different solvent of its reactive compound characteristic, and in our mouse liver toxicity animal It is screened in model.Following 19 kinds of plants in table 1 include the different piece belonged to from 16, are lured in mouse paracetamol The model or CCl led₄Show that the Serum ALT of different level inhibits in the model of induction.All there is work(only in two kinds of models The plant of effect will be selected for further studying.

Milk Thistle extract is prepared as the water extract of 80% ethyl alcohol of milk thistle (Silybum marianum) seed/20%, Extraction ratio is 40-50:1.The seed of the grinding water of 80% ethyl alcohol/20% is extracted, then by filtering by filter cake and supernatant Separation.Solvent is removed in a vacuum, obtains soft extract, it is mixed with maltodextrin and is further done with spray dryer It is dry.Milk Thistle extract is standardized total silymarin to meet no less than 50% and no less than 30% silibinin rule Lattice.Silymarin is made of the mixture of flavones lignan silibinin, silydianin and Silychristin.Silibinin is fine grinding The main active of silibin.The standardized extract of Semen Silybi mariani is commercially available.

As previously disclosed, N931 is 200 containing the 1-4% Aloesins and 96-99% that are blended by conventional method: The composition of the unique combination of 1 aloe vera internal lobe gel powder polysaccharide.Aloe vera internal lobe gel powder polysaccharide by Aloecorp with The form of freeze-dried powder provides.Crust is removed manually from the fresh clean leaf of aloe vera plant, then collects asparagus juice It is used in combination cellulase to handle so that enzyme inactivates.In enzyme inactivation, color is removed using activated carbon.By the filtrate after decoloration into One step is transferred in freeze-drying trap, is obtained aloe vera internal lobe gel powder, is blended with 1-4% Aloesins and N931 is made.

Table 1：The summary of plant extracts for the evaluation of internal liver protecting

Embodiment 4：Liver protecting activities of the plant extracts to the APAP and CCL4- hepatotoxicity models induced

The plant that (legacy mining) is excavated from legacy that liver protecting and newer history purposes are collected based on it 70% ethyl alcohol of object materials'use extracts, and screens it in APAP and CCl₄Effect in the hepatotoxicity of induction.Material is with table 2-3 Specified in dosage is oral gives animal.Although most plants extract shows the inhibition of Serum ALT in a model, But a small number of plants all show its effect in two kinds of models.Wherein, Schisandra chinensis, Artemisia capillaris, Milk Thistle and Loesyn are selected For further studying.

Table 2：In CCl₄The suppression percentage of the Serum ALT of plant extracts in the hepatotoxicity model of induction

Table 3：The suppression percentage of the Serum ALT of plant extracts in the hepatotoxicity model of APAP inductions

Embodiment 5：The dose-response effect of the plant extracts selected in APAP models

Method described above tests the mulberry leaves of 100,200 and 300mg/kg dosage in the hepatotoxicity model of APAP inductions (E1375), mulberry tree fruit (E1374), mulberry stem (E1377), Artemisia capillaris (R0594) and Schisandra chinensis (2%) (L0498).10% spits Temperature 20 is used as the carrier intermediate of all material.There is no the control mice of APAP only to receive medium (10% polysorbas20).Serum ALT is measured in T24.As shown in table 4 below, under the dosage of 300mg/kg, two plant material Schisandra chinensis (2%) (L0498) and mattress Old wormwood artemisia (R0594) shows that 36.8% and the 32.2% of Serum ALT levels inhibit respectively.These reductions are statistically significant.L0498 The survival rate of display 100% under the dosage of 300mg/kg, and R0594 has 90% survival rate.In lowest dose level (100mg/ Kg under), L0498 only shows 30% survival rate.And at this dose, R0594 has 70% survival rate.Do not consider dosage, institute There is the survival rate of mulberry extract down to 40.These high mortalities cause indefinite Serum ALT levels to reduce percentage.Therefore, In the model, Schisandra chinensis (2%) (L0498) and Artemisia capillaris (R0594) select object in being considered as really, in about 300mg/kg With optimal efficacy.

Table 4：Use the summary of the dose-response research of the hepatotoxicity model of APAP inductions

Embodiment 6：CCl₄The dose-response effect of the plant extracts selected in model

The hairyvein agrimony (E1399) of 400mg/kg, 300mg/kg and 200mgkg dosage and Loesyn (QMA2) and 400mg/kg and The Artemisia capillaris (R0594) of 300mg/kg dosage and Schisandra chinensis (2%) (L0498) are in CCl as described above₄The hepatotoxicity of induction It is tested in model.10% Tween-20 is used as the medium of all material.There is no CCl₄Control mice only receive medium (10% Tween-20).Serum ALT is measured in T24.

As shown in table 5 below, nearly all extract observes that the dosage correlation of Serum ALT levels reduces.With 400mg/kg Artemisia capillaris (R0594) (48.0%) then uses the mouse observation that the identical vegetable materials of 300mg/kg (29.9%) are treated again It is reduced to Serum ALT levels most.These reductions are statistically significant.In 400mg/kg, hairyvein agrimony and Loesyn are shown The reduction (i.e. 28%) of the ALT levels of closely similar level, P values are respectively 0.07 and 0.04.All groups of survivals for having 100% Rate includes the CCl4 controls of medium processing.At least in this batch, Artemisia capillaris (R0594) is in terms of inhibiting Serum ALT levels Display is better than selecting object in any other detection.

Table 5：Use CCl₄The dose study of the hepatotoxicity model of induction is summarized

Embodiment 7：The preparation of the organic extract of Artemisia capillaris

It by gas first portion Artemisia capillaris (2.5kg) cutting of drying and grinding, crushes, then uses 70% second of about 15 times of volumes (37.5L) Alcohol/water (v/v) extracts.Extraction carries out 3 hours at 85 DEG C.After filtering, ethanol solution is passed through into rotary evaporation under 40 DEG C of vacuum Device concentrates.The extraction and concentration processes are repeated with 70% ethanol/water (v/v) of 10 times of volumes (25L) twice, last 2 hours.It is logical It crosses vacuum drying chamber and the extract solution of concentration is evaporated to drying, obtain 70% ethanol extract powder (lot# of 480g Artemisia capillaris RN367-3-60M), extraction efficiency 19.2%.

Artemisia capillaris herbal medicine (180.4) g of dry grinding is extracted three times with 70% ethanol/water, every time reflux 1 hour.To have Machine solution merges and is evaporated in vacuo to provide 70% ethanol extract (R594-70EE) of 37.7g, yield 20.9%.Use phase Same program obtains similar as a result, but replacing organic solvent with methanol or ethyl alcohol to provide methanolic extract (ME) or second respectively Alcohol extracting thing (EE), ethyl alcohol:H₂O(7:3) extract, ethyl alcohol:H₂O(1:1) extract, ethyl alcohol:H₂O(3:7) extract and water carry Take object.The solvent extracting process is summarised in table 6.

Table 6：The solvent extraction of the gas first portion of Artemisia capillaris drying and grinding is summarized

Sample code	Extraction solvent	Extraction efficiency (%)
			R684-100EE	100% EtOH	11.7
R684-70EE	70% EtOH	19.2
			R684-50EE	50% EtOH	22.5
R684-30EE	30% EtOH	22.9
			R684-W	Water	25.7
R594-70EE	70% EtOH	20.9
			RN425-6-70EE	70% EtOH	17.9
RN425-7-70EE	70% EtOH	18
			RN425-8-70EE	70% EtOH	17.4
RN425-11-70EE	70% EtOH	19.2
			RN425-12-70EE	70% EtOH	19.2
RN425-13-70EE	70% EtOH	19.2
			RN425-14-70EE	70% EtOH	19.1

Embodiment 8：The classification separation of the bioassay guiding of oriental wormwood parthenium extract

By 70% ethanol extract of Artemisia capillaris, (RN425-7-70EE, 20 g) distribute between hexane (200mL) and water (250mL) Three times.Combined hexane solution obtains hexane extract (HE) 1.43g by the way that solvent is removed in vacuum.Aqueous layer with ethyl acetate (200mL) is extracted three times.Combined ethyl acetate layer is dried in vacuo, ethyl acetate extract (EA) 2.29g is obtained.Use butanol (200mL) further extraction water layer three times, obtains butanol extract (BU) 3.70g.Remaining water layer is freeze-dried, water is obtained Extract (WA) 15.3g.70%EE and HE, EA, BU and WA are in CCl₄It is tested in the mouse liver toxic model of induction.HE、 EA, BU are inactive, and 70%EE shows that 25.27% ALT inhibits in 400mg/kg, and WA fractions are shown when 300mg/kg levels 37.49% inhibits, P≤0.05.

Pass through the further isolating active fraction WA of HP20SS chromatographies.WA (4.4g) is dissolved in 20%EtOH/ water, and is loaded into With the pre-adjusted HP20SS of 20%EtOH/ water (Diaion, Mitsubishi Chemical Corporation, Japan, 160 g) columns.Column 800mL20%EtOH/ water, 600mL40%EtOH/ water, 400mL60%EtOH, 200mL80%EtOH Elution, is finally washed with 200mLEtOH and 200mL acetone.Collect two kinds of major fraction HP-01 (3.67g, 83.4%) and HP-02 It (305.7mg, 6.95%) and is tested in the hepatotoxicity mouse model of CCl4 inductions.The key component of HP-01 is oligosaccharides and more Sugar.HP-02 mainly contains polyphenol.Compared with the WA with 32.86% inhibition at 300mg/kg, HP-01 shows similar ALT inhibits.HP-02 is inactive in same model, shows that polyphenol does not contribute the activity of the plant.

Active fraction HP-01 opens column by LH-20 and further detaches.It is HP-01 (1.06g) is soluble in water and be loaded into A pre-adjusted LH-20 column in water obtains 4 fractions with MeOH/H2O gradient elutions, LH-01 (43.4 mg, 4.26%), LH-02 (799.6 mg, 78.5%), chlorogenic acid (LH-03,45.4 mg, 4.5%) and LH-04 (23.1 mg, 2.27%).Since sample limits, only major fraction LH-02 is tested in studying in vivo.LH-02,78.5% HP- 01 under 300mg/kg levels in CCl₄Without showing any effect in the animal model of induction.When with 200mg/kg horizontal checkouts When, chlorogenic acid (C3878, Sigma-Aldrich, USA) (ingredient of the HP-01 of about 4.5% ratio) does not show any suppression System.The intra-body data of this research clearly illustrates that the water-soluble component in addition to chlorogenic acid and polyphenol leads to the liver of parthenium extract Protection activity.Active polysaccharide content is less than the 10% of WA fractions.Table 7 summarizes the information.

Table 7：Liver protecting effect of R684-70EE fractions and compound

Sample code	Dosage (mg/kg)	CCl4 dosage	The % of ALT changes	P values
					R684-70EE	400	25	25.27	0.040
R684-HE	300	25	-2.26	0.864
					R684-EA	300	25	13.78	0.359
R684-BU	300	25	14.96	0.219
					R684-WA	300	25	37.49	0.003
HP-01	300	25	32.86	0.054
					HP-02	300	25	-10.03	0.537
LH-02	300	25	-0.73	0.961
					Chlorogenic acid	200	25	-24.14	0.192

Embodiment 9：Pass through film dialysis fraction isolating active HP-1 samples

By from Artemisia capillaris embodiment 8 and table 7 shown in liver protecting fraction-HP-01 be dissolved in the distillation of proper volume In water, and the opposite distilled water dialysis (cutoff 2000) in dialysis membrane tube, it 3 hours every time, carries out 3 times.By reservation It is lyophilized with combined dialysis solutions, obtains two sample DA-1 (MW>2000,13.79%) and DA-2 (MW<2000,84.54%). According to program identical with previous dialysis, by the further dialysis of DA-2, cutoff 500.Collect DA-3 (500<MW< 2000,16.7%) and DA-4 (MW<500,79.7%).DA-1, DA-3 and DA-4 are tested in the mouse model of CCl4 inductions.Point Son amount is most strong to the inhibiting effect of Serum ALT levels more than 2000 DA-1, has compared with DA-3 and DA-4 statistically significant Property.Less than 500 molecular weight without showing any effect in the In vivo model.Table 8 summarizes the information.

Table 8：Liver protecting effect of the dialysis sample of HP-01

Sample code	Molecular weight	Content %	Dosage (mg/kg)	CCl4 dosage	The % of ALT is reduced	P values
							DA-1	MW>2000	13.79%	300	25	47.47	0.04
DA-3	500<MW<2000	16.7%	300	25	39.19	0.09
							DA-4	MW <500	79.7%	300	25	-14.14	0.441

Embodiment 10：The HPLC of oriental wormwood parthenium extract is analyzed and is quantified

Based on lcms analysis and document report identify in oriental wormwood parthenium extract marker compounds chlorogenic acid (1, C3878, Sigma-Aldrich, USA) and two caffeoyls it is sour (2-3), and using C18 reversed-phase columns (Phenomenex, Luna C18,10 μm, 250 mm x, 4.6 mm) it is quantitative with the UV wavelength of 320nm in Hitachi HPLC systems.With 0.1% trifluoroacetic acid (TFA) binary gradient of/water and acetonitrile elutes pillar with 1mL/min flow velocitys.Based on reference compound chlorogenic acid quantitative combination object 1-3.Calculating based on peak area, from the chlorogenic acid content in the 70%EE of the Artemisia capillaris of separate sources collection in 1.5-4.8% (w/ W) variation in range.The information summary is in table 9-10.

Table 9：The HPLC gradient tables of wormwood artemisia analysis

Time (min)	0.1% TFA/H2O (%)	ACN (%)
			0	90	10
5	90	10
			15	80	20
30	60	40
			31	0	100
34	0	100
			34.1	90	10
40	90	10

Table 10：Chlorogenic acid * contents in 70% ethanol extract of Artemisia capillaris

Sample ID	1 (%)	2 (%)	3 (%)	Amount to 1-3 (%)
					R684-70EE	4.72%	3.57%	2.35%	10.63%
R594-70EE	1.56%	1.51%	0.72%	3.80%
					L0523	3.12%	1.48%	1.73%	6.33%
Honsea	2.31%	2.60%	3.32%	8.23%
					E1466	4.55%	3.02%	2.18%	9.76%
E1453	1.83%	1.17%	1.13%	4.13%
					RN425-6-70EE	4.17%	2.33%	2.07%	8.56%
RN425-7-70EE	3.97%	2.60%	2.34%	8.91%
					RN425-8-70EE	3.90%	2.57%	2.26%	8.73%
RN425-11-70EE	3.14%	3.30%	2.10%	8.54%
					RN425-12-70EE	5.05%	3.56%	2.52%	11.12%
RN425-13-70EE	3.60%	3.49%	2.02%	9.11%
					RN425-14-70EE	4.79%	4.12%	2.08%	11.00%

* chlorogenic acid is used as the n-compound at all three quantitative peaks (1-3)

Embodiment 11：The catechin of oriental wormwood parthenium extract is quantitative

The catechin in the water fraction (WA) of oriental wormwood parthenium extract is quantified by HPLC methods.Using with C18 reverse phases The Hitachi HPLC/PDA systems of column (4.6 mm of Phenomenex, USA, Luna 5 um, 250 mm x) carry out catechu Element detection and quantitative, flow velocity 1.0mL/min, column temperature are 35 DEG C, and UV wavelength is 275nm.It is not detected in all wormwood artemisia samples Epicatechin (E1753, Sigma-Aldrich, USA), and only low content catechin is based on catechin reference substance (C1251, Sigma-Aldrich, USA) is detected and quantified.Based on our In vivo study as a result, oriental wormwood parthenium extract The catechin content within the scope of 0.02-0.32% in WA fractions is unrelated with the liver protecting property of parthenium extract.The information is total Knot is in table 11-12.

Table 11：The gradient table of HPLC analysis methods

Time (min)	0.1% H3PO4/H2O (%)	ACN (%)
			0.0	85.0	15.0
7.0	85.0	15.0
			12.0	10.0	90.0
16.5	10.0	90.0
			16.6	85.0	15.0
24.0	85.0	15.0

Table 12：Catechin in parthenium extract is quantitative

Embodiment 12：Pass through film dialysis separating polyose

The Thick many candies of HP-01 from Artemisia capillaris are dissolved in the distilled water of proper volume, and the opposite steaming in dialysis membrane tube Distilled water dialysis (cutoff 2000) 3 hours every time, carries out 3 times.Reservation and combined dialysis solutions are lyophilized, are obtained Two samples, DA-1 (MW>And DA-2 (MW 2000,13.79%)<2000, 84.54%).In CCl₄The mouse model of induction Two samples of middle test.

Embodiment 13：Pass through gel osmoticing chromatogram analysis and quantitative polysaccharide

The active fraction WA of oriental wormwood parthenium extract is also analyzed by gel permeation chromatography, gel permeation chromatography is for commenting Estimate the generally acknowledged method of the molecular weight distribution of polysaccharide.With PolySep-SEC-P5000 columns (Phenomenex, OOH-3145KO Column, 300 mm x, 7.8 mm) pass through the Hitachi HPLC systems analysis Artemisia capillaris polysaccharide equipped with refractive index detector.Flowing It is mutually 0.1M NaCl, flow velocity 0.7mL/min, lasts 25 minutes.For each sample, 20 μ are injected with the concentration of 10mg/mL L.Based on six kinds of dextran molecule amount standard items (American Polymer Standards (American polymer Standards)), dividing For>2000,2000-1000,100-500,500-200,200-50,50-10,<Polysaccharide is determined within the scope of seven of 10 KDa Amount.The molecular weight distribution of the water fraction samples of different extracts is different.Liver protecting activities are related with higher molecular distribution.To the greatest extent Pipe total starches content is similar, but the distribution of weight of Artemisia capillaris sample is widely different.Larger polyoses content is higher, Artemisia capillaris observation To the effect of it is better.Molecular weight distribution is as shown in table 13.

Table 13：The molecular weight distribution of biopolymer in parthenium extract

MW is distributed (kDa)	>2000	2000-1000	1000-500	500-200	200-50	50-10	< 10	PSD (%)
									E1453-WA	1.2	6.6	11.7	16.9	38.2	25.3	0	0.36
L523-WA	0	0	0	13	82.7	4.3	0	0.33
									E1466-WA	60.9	14.2	14.6	10.2	0.1	0	0	0.30
R594-WA	0	0	0	0	0	0	0	0.31

Embodiment 14：Artemisia capillaris fraction is to CCl₄The liver protecting activities of model

Utilize CCl₄The hepatotoxicity model of induction is evaluated in hexane (HE), ethyl acetate (EA), butanol (BU) and water The liver protecting activities of Artemisia capillaris fraction.Control mice only receives 10% Tween-20.Serum ALT is measured in T24.Although wormwood artemisia fraction It is given with the dosage of 300mg/kg, but starting material is given with the dosage of 400mg/kg.

As shown in table 14, the mouse treated with the water fraction of the wormwood artemisia of 300mg/kg dosage observes that the highest of Serum ALT presses down System, shows there is active marker in the fraction.It is however not excluded there are other activity in other fractions Marker.Original material (R684) is with its effect of the dose maintenance of 400mg/kg.All groups in this model have 100% Survival rate.

Table 14：The activity of Artemisia capillaris fraction

Group	N	Material	ID	Dosage (mg/kg)	CCl4 (µl/kg)	% ALT variations	PValue
								G-1	5	It compares (-)	-	0	0	-	-
G-2	10	CCl4	-	0	25	-	-
								G-3	10	R684-HE	RN425-7-HE	300	25	-2.3	0.864
G-4	10	R684-EA	RN425-7-EA	300	25	13.8	0.359
								G-5	10	R684-BU	RN425-7-BU	300	25	15.0	0.219
G-6	10	R684-WA	RN425-7-WA	300	25	37.5	0.003
								G-7	10	R684	R684	400	25	25.3	0.040

Embodiment 15：The preparation of schisandra fruit organic extract

It 20g Schisandra chinensis dry fruit will be fitted into two 100ml stainless steel tubes, and be existed using 300 automatic extractors of ASE in total It is extracted twice under 80 degree and with organic 70%EtOH/ water under 1500psi pressure.Extract solution automatic fitration and collection.Pass through rotation Combined solution is evaporated to drying by evaporator, obtains crude 70%EtOH extracts (9.65g, 49.5%).

Obtain similar using identical program as a result, but replacing organic solvent with methanol or ethyl alcohol to provide methanol respectively Extract (ME) or ethanol extract (EE), ethyl alcohol:H₂O(7:3) extract, ethyl alcohol:H₂O(1:1) extract, ethyl alcohol:H₂O(3: 7) extract and water extract.

Schisandra chinens P.E is prepared with water (v/v) the extraction dry fruit of 70% ethyl alcohol/30%.Extract is further processed to obtain To the extract (Lot#) of powder type, there is no less than 2% total schizandrin, including schizandrin, Schisantherin A, Schisandra chinensis Plain A (deoxidation schizandrin) and wuweizisu B.

Embodiment 16：The HPLC of Schisandra chinens P.E is analyzed and is quantified

Four kinds of activity mark compounds schizandrin (lot #110857, National Institute for Food and Control, China)、schisantherin A (lot #11529-200503, National Institute for Food and Control, China), wuweizisu A (deoxidation schizandrin, lot #110764-200107, National Institute for Food and Control, China) and wuweizisu B (lot #110765-200508, National Institute for Food and Control, China) it is accredited in Schisandra chinens P.E, it is used in combination five Taste reference standard substance (lot#140217, National Institute for Food and Control, China) It confirms.

By HPLC come qualitative activity marker compounds, C18 reversed-phase columns are used in Hitachi HPLC systems (Phenomenex, Luna C18,10 μm, 250 mm x, 4.6 mm), using the UV wavelength of 250nm, by with reference to marking Quasi- material relatively carries out.Pillar is eluted with the flow velocity of 1mL/min with water and acetonitrile.Table 15 shows the gradient of the embodiment Table.Each peak is identified and is integrated, be then based on RSM calculate four kinds of compounds total content, including schizandrin, Schisantherin A, wuweizisu A and wuweizisu B, the information are as shown in table 16.

Table 15：The quantitative HPLC eluent gradient tables of Schisandra chinens P.E

Time (min)	H2O (%)	ACN (%)
			0	40	60
10	20	80
			25	0	100
30	0	100
			30.1	40	60
35	40	60

Table 16：The content of schizandrin in Schisandra chinens P.E

Sample code	Schizandrin	schisantherin A	Deoxidation schizandrin	Wuweizisu B	Total schizandrin
						L531	0.03%	0.87%	0.07%	0.04%	1.01%
L0498	1.16%	0.10%	0.23%	0.58%	2.07%
						L499	3.80%	0.69%	0.77%	1.84%	7.10%

Embodiment 17：The HPLC of organic acid is quantitative in schisandra fruit extract

By different collections inside generate 70%EtOH extracts in malic acid, shikimic acid and citric acid presence by Confirmation is listed in table 17.By HPLC quantitative analysis organic acids, Hypersil GOLD aQ columns (4.6x250mm, 5 μ are used M) it is carried out 20 minutes at 5 DEG C under isocratic condition, (H is used with 50mM potassium dihydrogen phosphates₃PO₄2.8) pH is adjusted to as flowing Phase, flow velocity 0.7ml/min.Organic acid is detected at 205nm using UV detectors, and passes through the base compared with organic acid standard items It is identified in retention time.

Table 17：The HPLC of organic acid content is quantitative in Schisandra chinens P.E

Embodiment 18：Wormwood artemisia and Schisandra chinens P.E in various combination are used for APAP and CCl₄Liver protecting in model

Once the guide plant of such as Artemisia capillaris and Schisandra chinensis has been selected, in APAP and CCl₄In the hepatotoxicity model of induction with 4:1,2:1,1:1,1:2 and 1:Their effects in liver protecting of 4 various combination ratio estimation.Two kinds of plants are applied in combination The first letter of each plant is encoded to " SA ", i.e., " S " is Schisandra chinensis, and " A " is Artemisia capillaris.As shown in table 18 below, although institute There is blend to show certain liver protection, when with the 2 of Schisandra chinensis and wormwood artemisia:The blend of 1 ratio is with the total of 400mg/kg When dosage treatment mouse, 48.0% reduction measured by Serum ALT levels is observed, for the maximum with significance,statistical Protective effect.Similarly, in CCl₄In model, when with the 1 of Schisandra chinensis and wormwood artemisia:The blend of 2 ratios is with the total of 400mg/kg When dosage treatment mouse, 40.6% reduction measured by Serum ALT levels is observed, for the maximum with significance,statistical Liver protection.In the two models, the survival rate under this specific ratios is all 100%.

Table 18：Composition SA is in APAP/CCl₄Effect in the hepatotoxicity model of induction

When Schisandra chinensis and wormwood artemisia are with 2S:1A (APAP models) and 1S:2A(CCl₄Model) be blended when, observe highest liver protecting Effect.As a result, these ratios are considered as middle choosing.

Embodiment 19：The preparation of combination S AL compositions

By the way that 320g is blended with 30rpm with belt blender (Ribbon blender) (Hankook P.M. EMG, Korea) Schisandra chinens P.E (lot #E1458), 263g parthenium extracts (lot#RN425-13), 377g parthenium extracts (lot#RN425- 14) and the N931 of 240g (2% Aloesins of E1459) 1 hour, to obtain the ratio of 1.17 kg as Schisandra chinensis:Wormwood artemisia:N931=4: 8:The SAL combinations (lot#RN425-1501) of 3 weight, to prepare expected SAL groups polymeric composition (lot#RN425-1501).

Embodiment 20：Evaluate APAP/CCl₄The liver protecting activities of the blend of Schisandra chinensis, Artemisia capillaris and N931 in model

Select 2S:1A (APAP models) and 1S:2A (CCl₄Model) Schisandra chinensis and Artemisia capillaris two kinds of guide's blend ratios Rate obtains further liver protecting activities, is named as SAL by adding the third guide's component (Loesyn)." L " is represented Loesyn.N931 is added to 2S with 10,20 and 30% weight ratio:1A is combined, and 1S is added to 10,20 and 25% weight ratio:2A groups It closes.The composition is in APAP/CCl₄It is tested in the hepatotoxicity model of induction.Mouse is with composition SAL with 400mg/kg Dosage treatment.Although all compositions of different ratios show a degree of liver protecting, as shown in table 19, when with point Not Wei the SAL of 400mg/kg dosage of 106.7/213.3/80 ratios when treating mouse, it is most to observe that Serum ALT reduces (51.9%, P=0.01), therefore protective effect is maximum.In this model, there is 100% survival rate under this specific ratio.

Similarly, although all compositions of different ratios show a degree of liver protecting, as shown in table 19, when When treating mouse with the SAL of the 400mg/kg dosage of respectively 106.7/213.3/80 ratios, it is most to observe that Serum ALT reduces (42.3%, P=0.01).In this model, there is 100% survival rate under this specific ratio.

Table 19：Composition SAL is in APAP/CCl₄Effect in the hepatotoxicity model of induction

Although numerous compositions show liver-protective effect, when 1S is added in two kinds of models in 20% weight Loesyn: 2A ratios obtain the final 4S of composition SAL:8A:When the ratio of 3L, highest protection is observed.As a result, ratio 4S:8A: 3L is considered as antecedent composition.

Embodiment 21：In APAP and CCl₄In the hepatotoxicity model of induction, include the group of Schisandra chinensis, Artemisia capillaris and N931 Close the dose-response effect of object

In APAP and CCl₄The optimal dose for the composition SAL that can cause notable liver protecting is had evaluated in the model of induction.It is small Mouse oral gavage composition SAL, dosage 400mg/kg, 325mg/kg and 250mg/kg are suspended in 10% Tween-20.Medium Object control group only receives carrier solution.As shown in table 20, in APAP groups, composition observes the dosage correlation of Serum ALT Inhibit.Observe 52.5% respectively with the mouse of the dosage treatment of 400mg/kg, 325mg/kg and 250mg/kg SAL (p= 0.001), the inhibition of 48.5% (p=0.012) and 34.6% (p=0.079).Similarly, in CCl₄In group, composition is observed The dosage correlation of Serum ALT inhibits.With the mouse difference of the dosage treatment of 400mg/kg, 325mg/kg and 250mg/kg SAL Observe the inhibition of 46.3% (p=0.003), 39.5% (p=0.007) and 29.9% (p=0.036).It is all in two models Group has 100% survival rate.Composition SAL is with down to the dosage level of 250mg/kg, ratio 1S:2A and have 20% L When, provide (CCL4) hepar damnification protection of significance,statistical.

Herein, we test the effect of each plant such as Schisandra chinensis, wormwood artemisia and Loesyn, and dosage is equal to each plant Ratio in composition SAL, as they with highest proof load (400mg/kg) with 4S:8A:The ratio of 3L occurs.Such as table Shown in 20, the survival rate of the inhibiting rate and 70-80% of these plants average 20% is observed under given dose.

Table 20：APAP/CCl₄The dosage correlation liver protecting of composition SAL in the hepatotoxicity model of induction

Embodiment 22：The assessment of composition SAL synergistic effects

Combined five-taste, Artemisia capillaris and N931 are had evaluated in APAP and CCL4 models using Colby equations (Colby, 1967) Benefit.As shown in table 21 below, the both greater than expected assumption value (A+B-C) of the value observed in two kinds of models, shows with spy There is synergistic effect when fixed-ratio prepares three kinds of ingredients to generate SAL.By it for by APAP and CCl₄Caused liver damage The coordinating protection of wound, it was confirmed that the advantages of Schisandra chinensis, wormwood artemisia and N931 is blended.

Table 21：The unexpected synergistic activity of Schisandra chinensis, Artemisia capillaris and N931 in liver protecting.

Embodiment 23：Liver protecting activities of the SAL compositions with respect to its each component that dosage is 300mg/kg

Utilize APAP and CCl₄It is each with respect to its to compare the SAL compositions that dosage is 300mg/kg for the hepatotoxicity model of induction The liver protecting activities of component, using the Serum ALT levels of reduction as the measurement of effect.10% Tween-20 is used as all materials The carrier intermediate of material.Control mice only receives Tween-20.Other than Serum ALT, control, APAP/ are also measured in T24 CCl₄, SAL liver function panel such as T albumen, T bilirubin, albumin, AST and bile acid.

Table 22：Dosage is the composition SAL of 300mg/kg and each component in APAP and CCl₄The hepatotoxicity mould of induction Serum ALT levels in type

As seen in table 23 and 24, measurements of the AST as effect, composition (SAL) is shown in APAP models compares medium The hepar damnification protective effect (i.e. 60.6%) of object enhancing.Compared with mediator object group, with SAL, S (Schisandra chinensis), A (wormwood artemisia) and L (N931) mouse treated observes 47.1,42.2,42.0 and 16.6% statistically significant reduction of Serum ALT respectively.It is right Minimum survival rate (50%) is observed in the mouse treated with wormwood artemisia.

Confirm APAP models as a result, composition SAL in CCl₄It is shown than every with the dosage of 300mg/kg in model The liver protection of kind independent component bigger, using Serum ALT as the measurement of effect.In addition, using AST as effect Measurement, composition (SAL) show the injury protection (that is, 32.5%) enhanced than medium.All groups of depositing in this model Motility rate is all 100%.

Table 23：Liver function panel marker in APAP models compared with the mouse of medium processing

As shown in table 24, compared with the APAP positive mices of medium processing, composition SAL shows improvement in APAP models Liver associated biomarkers, such as bile acid, T. bilirubin and T. albumen.Similarly, compared with medium group, CCl₄Mould In type statistically significant bile acid clearance rate is observed with the mouse of composition SAL treatments.

Table 24：In CCl₄Liver function panel marker in model compared with the mouse of medium processing

Embodiment 24：The effect of composition SAL, confirms research in the hepatotoxicity model of APAP and CCL4 inductions

The superiority for demonstrating the liver protecting activities of composition SAL, uses APAP and CCl₄The hepatotoxicity model of induction into Row confirmation research.Mouse oral tube feed 400mg/kg compositions SAL.10% Tween-20 is used as the carrier medium of all material Object.Control mice only receives Tween-20.Other than Serum ALT, control, APAP/CCl are also measured in T24₄, SAL liver Function panel such as T. albumen, total bilirubin, bili,D/I, albumin, globulin, AST, bile acid and ALP.

As shown in the following table 25 and 26, observe Serum ALT, AST with the mouse of composition SAL treatment, in conjunction with bilirubin and The statistically significant inhibition of bile acid.These inhibiting effect are to reduce by 34.0%, 44.5%, 60.0% and than medium processing group 26.7%.Similarly, compared with the mouse of medium processing, composition SAL shows the statistically significant drop of Serum ALT levels Low (reducing by 44.0%) and AST strong reduction trend (reducing by 35.9%).In general, composition SAL is in a variety of conventional animals The hepar damnification protection of bigger is provided in model, as shown in table 27.

Table 25：In the hepatotoxicity model of APAP inductions, with the liver function Panel Data object water of the mouse of SAL treatments Flat summary.

Table 26：In CCl₄In the hepatotoxicity model of induction, with the liver function Panel Data object water of the mouse of SAL treatments Flat summary.

Table 27：In APAP/CCl₄In model, the liver function panel mark of SAL groups compared with the mouse of medium processing The summary of the percentage variation of object.

(+):↓ relative to APAP/CCl₄(+) medium is reduced

(-):↑ relative to APAP/CCl₄(+) medium increases

Embodiment 25：Composition SAL is to from CCl₄Oxidative stress life in the liver homogenate that the hepatotoxicity model of induction is collected The influence of object marker

Use CCl₄The hepatotoxicity model of induction carries out additional confirmation and measures to assess composition SAL in protecting liver Effect.Mouse oral tube feed 400mg/kg compositions SAL.Using 10% polysorbas20 as carrier intermediate.Control mice only receives Polysorbas20.Liver organization is collected after autopsy immediately to be placed in dry ice until being transferred to -80 DEG C.Then by material in dry ice In be transported to contract laboratory (Brunswick Laboratories, 200 Turnpike Rd, MA 01772, USA) use In final sample processing and biomarker analysis.Assess liver glutathione (GSH) and superoxide dismutase (SOD).

Glutathione (GSH) is intracellular three peptide thiol of key, passes through offer and restores equivalent reduction lipid hydrogen peroxide Compound helps prevent cell by radical damage.In the process, oxidized form of glutathione (GSSG) is used as reaction product shape At.GSH levels have been used as the indicative biomarker of vivo oxidation agent and cell and tissue oxygen stress level.Herein In analysis, sulfydryl and DTNB (5,5 '-two sulphur-bis- -2- (the nitrobenzoic acid)) reactions of GSH generate yellow 5- sulfydryl -2- nitros Benzoic acid (TNB) product.The amount of GSH is determined by measuring the absorbance of the TNB at 410nm in biological sample.

Superoxide dismutase (SOD) is the metal for being catalyzed superoxide anion and being disproportionated into molecular oxygen and hydrogen peroxide Enzyme.SOD is considered as one of internal most important antioxidase.SOD measuring methods are colorimetric methods, are surveyed using tetrazolium salts The disproportionation for the superoxide radical that amount is induced by xanthine oxidase and xanthine, and generated by using SOD reference substances Standard curve quantify the activity of SOD in given sample.The SOD of one unit is defined as display superoxide radical 50% Enzyme amount needed for disproportionation.

As shown in table 28 below, using every gram of protein level of the biomarker of each test, composition SAL is supplemented The liver glutathione of consumption, combines and increases Liver Superoxide Dismutase Activity.These find and previously disclosed liver function Panel data shows that composition SAL has the liver for oxidative stress caused by the hepar damnification induced by CCL4 strongly together Dirty protection activity.

Table 28：Use the oxidative stress biomarker level of the composition SAL mouse liver homogenate treated

Embodiment 26：The blend of the Radix Astragalis of specific ratios, Schisandra chinensis and Artemisia capillaris is in CCl₄In the hepatotoxicity model of induction Liver protecting activities assessment

Also in CCl₄The group being made of two kinds of other guide's plant extracts is had evaluated in the mouse liver toxic model of induction The liver protecting activities of conjunction.Radix Astragali (Astragalus Membranous) with Schisandra chinensis or Artemisia capillaris with 1:1、1:2、2:1、1:4 With 4:1 ratio combine.As shown in table 29, when Radix Astragali is blended with Schisandra chinensis, compared with the damage mouse of medium processing, only There is a kind of ratio i.e. 1:The reduction of 4 display Serum ALTs statistically non-limiting (34.1%).In contrast, when Radix Astragali and wormwood artemisia group When conjunction, the liver protecting of higher degree is observed.2:1 and 4:The Radix Astragali of 1 ratio:Wormwood artemisia observes that Serum ALT statistics is aobvious respectively 46.3% and 57.7% inhibition write.There is 100% survival rate under all ratios tested in this model.

Table 29：Mouse in the hepatotoxicity model that Radix Astragali, Schisandra chinensis and the CCL4 of Artemisia capillaris treatment of specific ratios are induced The Data Summary of Serum ALT levels

Therefore, it has been disclosed that the specific embodiment and method of compound and composition for liver health management, including public affairs The stereoisomer of compound, acceptable salt, tautomer, glucosides and prodrug pharmaceutically or in health care are opened, and is improved With the correlation technique for maintaining liver health.It is apparent, however, to one skilled in the art, that in the hair for not departing from this paper In the case of bright design, other than those of having been described, can also more it be changed.Therefore, subject of the present invention It is unrestricted, in addition in scope disclosed herein.In addition, when illustrating book and claims, all terms Should by it is consistent with the context it is broadest it is possible in a manner of explain.Specifically, term " comprising " and "comprising" should be solved Be interpreted as referring to element, component or step in a manner of nonexcludability, indicate mentioned element, component or step can be not known Other elements, component or the step referred to exist together, utilization or combination.

Bibliography

The bibliography being listed below is the complete reference for the bibliography having disclosed herein.It should be noted that this Each in a little bibliography is incorporated herein by reference in their entirety.

1.Ajith TA, Hema U, Aswathy MS. Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status. Food Chem. Toxicol. 2007; 45:2267–2272.

2.Albano E., Lott A.K., Slater T.F., Stier A., Symons M.C.R., and Tomasi A. (1982) Spin trapping studies on the free radical products formed by metabolic activation of carbon tetrachloride in rat liver microsomal fractions, isolated hepatocytes and in vivo. Biochem. J. 204:593–603.

3.Amat N, Upur H, Blazeković B. In vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. against chemically and immunologically induced liver injuries in mice. J Ethnopharmacol. 2010; 131 (2):478-84

4.An RB, Sohn DH, Kim YC. Hepatoprotective compounds of the roots of Cudrania tricuspidata on tacrine-induced cytotoxicity in Hep G2 cells. Biol Pharm Bull. 2006; 29(4):838-40.

5.Bajt ML, Cover C, Lemasters JJ, Jaeschke H. Nuclear translocation of endonuclease G and apoptosisinducing factor during acetaminophen-induced liver cell injury. Toxicol. Sci. 2006; 94:217–225.

6.Bajt ML, Farhood A, Lemasters JJ, Jaeschke H. Mitochondrial bax translocation accelerates DNA fragmentation and cell necrosis in a murine model of acetaminophen hepatotoxicity. J. Pharmacol. Exp. Ther. 2008; 324:8– 14.

7.Bajt ML, Ramachandran A, Yan HM, Lebofsky M, Farhood A, Lemasters JJ, Jaeschke H. Apoptosisinducing factor modulates mitochondrial oxidant stress in acetaminophen hepatotoxicity. Toxicol. Sci. 2011; 122:598–605.

8.Cha JD, Moon SE, Kim HY, Lee JC, Lee KY. The essential oil isolated from Artemisia Capillaris prevents LPS-induced production of NO and PGE(2) by inhibiting MAPK-mediated pathways in RAW 264.7 macrophages. Immunol Invest. 2009; 38:483–97.

9.Chamulitrat W., Blazka M.E., Jordan S.J., Luster M.I., and Mason R.P. (1995) Tumor necrosis factor-alpha and nitric oxide production in endotoxin- primed rats administered carbon tetrachloride. Life Sci. 57:2273–2280.

10.Chamulitrat W., Jordan S.J., and Mason R.P. (1994) Nitric oxide production during endotoxic shock in carbon tetrachloride-treated rats. Mol. Pharmacol. 46:391–397.

11.Cheeseman K.H., Davies M.J., Emery S., Maddix S.P., and Slater T.F. (1987) Effects of alpha-tocopherol on carbon tetrachloride metabolism in rat liver microsomes. Free Radic. Res. Commun. 3:325–330.

12.Choi JH, Kim DW, Yun N, Choi JS, Islam MN, Kim YS, et al. Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice. J Nat Prod. 2011; 74:1055–60.

13.Choi MK, Han JM, Kim HG, Lee JS, Lee JS, Wang JH, Son SW, Park HJ, Son CG. Aqueous extract of Artemisia capillaris exerts hepatoprotective action in alcohol-pyrazole-fed rat model. J Ethnopharmacol. 2013; 147(3): 662-70

14.Chu CY, Tseng TH, Hwang JM, Chou FP, Wang CJ. Protective effects of capillarisin on tert-butylhydroperoxide-induced oxidative damage in rat primary hepatocytes. Arch Toxicol. 1999; 73:263–8.

15.Colby, SR. Calculating Synergistic and Antagonistic Responses of Herbicide combinations. Weeds, Vol. 15, No. 1 (Jan., 1967), pp. 20-22.

16.Cover C, Mansouri A, Knight TR, Bajt ML, Lemasters JJ, Pessayre D, Jaeschke H. Peroxynitriteinduced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity. J. Pharmacol. Exp. Ther. 2005; 315:879–887.

17.Czaja M.J., Xu J., and Alt E. (1995) Prevention of carbon tetrachloride-induced rat liver injury by soluble tumor necrosis factor receptor. Gastroenterology 108:1849–1854.

18.Davern TJ 2nd, James LP, Hinson JA, Polson J, Larson AM, Fontana RJ, Lalani E, Munoz S, Shakil AO, Lee WM, Acute Liver Failure Study Group. Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Gastroenterology. 2006; 130:687–694

19.Feng G, Wang X, You C, Cheng X, Han Z, Zong L, Zhou C, Zhang M. Antiproliferative potential of Artemisia capillaris polysaccharide against human nasopharyngeal carcinoma cells. Carbohydr Polym. 2013; 15; 92(2):1040- 5.

20.Han KH, Jeon YJ, Athukorala Y, Choi KD, Kim CJ, Cho JK, et al. A water extract of Artemisia Capillaris prevents 2,2’-azobis(2-amidinopropane) dihydrochloride-induced liver damage in rats. J Med Food. 2006; 9:342–7.

21.Hanawa N, Shinohara M, Saberi B, Gaarde WA, Han D, Kaplowitz N. Role of JNK translocation to mitochondria leading to inhibition of mitochondria bioenergetics in acetaminophen-induced liver injury. J. Biol. Chem. 2008; 283:13565–13577.

22.He CS, Yue HY, Xu J, Xue F, Liu J, Li YY, Jing HE. Protective effects of capillary artemisia polysaccharide on oxidative injury to the liver in rats with obstructive jaundice. Exp Ther Med. 2012; 4(4):645-648.

23.Hogade MG, Patil ks, Wadkar GH, Mathapati SS, Dhumal P. Hepatoprotective activity of Morus alba (Linn.) leaves extract against carbon tetrachloride induced hepatotoxicity in rats. African Journal of Pharmacy and Pharmacology 2010; Vol. 4(10), pp. 731-734,

24.Hong JH, Lee IS. Cytoprotective effect of Artemisia Capillaris fractions on oxidative stress-induced apoptosis in V79 cells. Biofactors. 2009; 35:380–8.

25.Hong SH, Seo SH, Lee JH, Choi BT. The aqueous extract from Artemisia capillaris Thunb. Inhibits lipopolysaccharide-induced inflammatory response through preventing NF-kappaB activation in human hepatoma cell line and rat liver. Int J Mol Med. 2004; 13(5):717-20.

26.Hu YQ, Tan RX, Chu MY, Zhou J. Apoptosis in human hepatoma cell line SMMC-7721 induced by water-soluble macromolecular components of Artemisia capillaris Thunberg. Jpn J Cancer Res. 2000; 91(1):113-7.

27.Hung HY, SC. Recent Studies and Progression of Yin Chen Hao (mattress Chan wormwood artemisia Y ī n Chén Hāo), a Long-term Used Traditional Chinese Medicine. J Tradit Complement Med. 2013; 3(1): 2–6.

28.Jaeschke H, McGill MR, Ramachandran A. Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. Drug Metab. Rev. 2012a; 44:88–106.

29.Jaeschke H, Williams CD, McGill MR, Xie Y, Ramachandran A. Models of drug-induced liver injury for evaluation of phytotherapeutics and other natural products. Food Chem Toxicol. 2013 May;55:279-89.

30.Jaeschke H. Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol. J. Pharmacol. Exp. Ther. 1990; 255:935–941.

31.James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab. Dispos. 2009; 37:1779–1784.

32.Jollow DJ, Mitchell JR, Potter WZ, Davis DC, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo. J. Pharmacol. Exp. Ther. 1973; 187:195 – 202.

33.Jung HA, Park JJ, Islam MN, Jin SE, Min BS, Lee JH, et al. Inhibitory activity of coumarins from Artemisia Capillaris against advanced glycation end product formation. Arch Pharm Res. 2012; 35:1021–35.

34.Kim DW, Cho HI, Kim KM, Kim SJ, Choi JS, Kim YS, et al. Isorhamnetin-3-O- galactoside protects against CCl4-Induced hepatic injury in mice. Biomol Ther. 2012; 20:406–12.

35.Kim EK, Kwon KB, Han MJ, Song MY, Lee JH, Lv N, et al. Inhibitory effect of Artemisia Capillaris extract on cytokine-induced nitric oxide formation and cytotoxicity of RINm5F cells. Int J Mol Med. 2007; 19:535–40.

36.Kim SW, Kim HW, Woo MH, Lee JH, Choi JS, Min BS. Quantitative determination of bioactive compounds in some Artemisia capillaris by high- performance liquid chromatography. Nat Prod Sci. 2010; 16(4):233-238

37.Kon K, Kim JS, Jaeschke H, Lemasters JJ. Mitochondrial permeability transition in acetaminopheninduced necrosis and apoptosis of cultured mouse hepatocytes. Hepatology. 2004; 40:1170–1179.

38.Koo HN, Hong SH, Jeong HJ, Lee EH, Kim NG, Choi SD, et al. Inhibitory effect of Artemisia Capillaris on ethanol-induced cytokines (TNF-α, IL-1α) secretion in Hep G2 cells. Immunopharmacol Immunotoxicol. 2002; 24:441–53.

39.Kwon OS, Choi JS, Islam MN, Kim YS, Kim HP. Inhibition of 5- lipoxygenase and skin inflammation by the aerial parts of Artemisia Capillaris and its constituents. Arch Pharm Res. 2011; 34:1561–9.

40.Larson AM. Acetaminophen hepatotoxicity. Clin. Liver Dis. 2007; 11: 525–548.

41.Lee HI, Seo KO, Yun KW, Kim MJ, Lee MK. Comparative study of the hepatoprotective and Artemisia capillaris on efficacy of Artemisia iwayomogi ethanol-administered mice. J Food Sci. 2011; 76(9):T207-11

42.Loguidice A, Boelsterli UA. Acetaminophen overdose-induced liver injury in mice is mediated by peroxynitrite independently of the cyclophilin D-regulated permeability transition. Hepatology. 2011; 54:969–978.

43.Luckey S.W. and Petersen D.R. (2001) Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats. Exp. Mol. Pathol. 71:226–240.

44.Masubuchi Y, Suda C, Horie T. Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice. J. Hepatol. 2005; 42:110–116.

45.McGill MR, Sharpe MR, Williams CD, Taha M, Curry SC, Jaeschke H. The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J. Clin. Invest. 2012a; 122:1574–1583.

46.McGill MR, Williams CD, Xie Y, Ramachandran A, Jaeschke H. Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicol. Appl. Pharmacol. 2012b; 264:387–394.

47.Mitchell JR, Jollow DJ, Potter WZ, Davis DC, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J. Pharmacol. Exp. Ther. 1973; 187:185–194.

48.Nakagawa H, Maeda S, Hikiba Y, Ohmae T, Shibata W, Yanai A, Sakamoto K, Ogura K, Noguchi T, Karin M, Ichijo H, Omata M. Deletion of apoptosis signal-regulating kinase 1 attenuates acetaminophen-induced liver injury by inhibiting c-Jun N-terminal kinase activation. Gastroenterology. 2008; 135: 1311–21.

49.Nelson S.D. and Harrison P.J. (1987) Roles of cytochrome P450 in chemically induced cytotoxicity. In: Guengrich F.P. (Ed.), Mammalian Cytochromes P450, CRC Press, Boca Raton, pp. 19–80.

50.Panossian A, Wikman G. Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol. 2008; 118(2):183-212.

51.Park KM, Li Y, Kim B, Zhang H, Hwangbo K, Piao DG, Chi MJ, Woo MH, Choi JS, Lee JH, Moon DC, Chang HW, Kim JR, Son JK. High-performance liquid chromatographic analysis for quantitation of marker compounds of Artemisia capillaris Thunb. Arch Pharm Res. 2012; 35(12):2153-2162

52.Poyer J.L., McCay P.B., Lai E.K., Janzen E.G., and Davis E.R. (1980) Confirmation of assignment of trichloromethyl radical spin adduct detected by spin trapping during 13C carbon tetrachloride metabolism in vitro and in vivo. Biochem. Biophys. Res. Commun. 94:1154–1160.

53.Qiu Y, Benet LZ, Burlingame AL. Identification of hepatic protein targets of the reactive metabolites of the non-hepatotoxic regioisomer of acetaminophen, 3′-hydroxyacetanilide, in the mouse in vivo using two- dimensional gel electrophoresis and mass spectrometry. Adv. Exp. Med. Biol. 2001; 500:663–673.

54.Ramachandran A, Lebofsky M, Baines CP, Lemasters JJ, Jaeschke H. Cyclophilin D deficiency protects against acetaminophen-induced oxidant stress and liver injury. Free Radic. Res. 2011a; 45:156–164.

55.Renner H. (1985) The limited relevance of models used for testing human hepatic diseases and their prevention. In: Keppler E., Popper H., Bianchi L., and Reutter W. (Eds.), Mechanisms of Hepatocyte Injury and Death, MTP Press Ltd., Lancaster, pp. 311–320.

56.Reynolds E.S. (1963) Liver parenchymal cell injury. I. Initial alterations of the cell following poisoning with carbon tetrachloride. J. Cell Biol. 19:139–157.

57.Saito C, Lemasters JJ, Jaeschke H. c-Jun N-terminal kinase modulates oxidant stress and peroxynitrite formation independent of inducible nitric oxide synthase in acetaminophen hepatotoxicity. Toxicol. Appl. Pharmacol. 2010a; 246:8–17.

58.Singab AN, Ayoub NA, Ali EN, Mostafa NM. Antioxidant and hepatoprotective activities of Egyptian moraceous plants against carbon tetrachloride-induced oxidative stress and liver damage in rats. Pharm Biol. 2010; 48(11):1255-64.

59.Slater T.F. (1981) Activation of carbon tetrachloride:chemical principles and biological significance. In: McBrien D.C.H., Slater T.F. (Eds.), Free Radicals, Lipid Peroxidation and Cancer, Academic Press, London, pp. 243–270.

60.Tien YC, Liao JC, Chiu CS, Huang TH, Huang CY, Chang WT, et al. Esculetin ameliorates carbon tetrachloride-mediated hepatic apoptosis in rats. Int J Mol Sci. 2011; 12:4053–67.

61.Tirmenstein MA, Nelson SD. Subcellular binding and effects on calcium homeostasis produced by acetaminophen and a nonhepatotoxic regioisomer, 3′- hydroxyacetanilide, in mouse liver. J. Biol.Chem. 1989; 264:9814–9819.

62.Wan Y, Wu YL, Lian LH, Nan JX. Protective effect of Ornithogalum saundersiae Ait (Liliaceae) against acetaminophen-induced acute liver injury via CYP2E1 and HIF-1α. Chin. J. Nat. Med. 2012; 10:177–184.

63.Wang JH, Choi MK, Shin JW, Hwang SY, Son CG. Antifibrotic effects of Artemisia capillaris and Artemisia iwayomogi in a carbon tetrachloride- induced chronic hepatic fibrosis animal model. J Ethnopharmacol. 2012;140(1): 179-85.

64.Weddle CC, Hornbrook KR, McCay PB. Lipid peroxidation and alteration of membrane lipids in isolated hepatocutes exposed to carbon tetrachloride. J. Biol. Chem. 1976; 251:4973–4978.

65.Yang CC, Fang JY, Hong TL, Wang TC, Zhou YE, Lin TC. Potential antioxidant properties and hepatoprotective effects of an aqueous extract formula derived from three Chinese medicinal herbs against CCl(4)-induced liver injury in rats. Int Immunopharmacol. 2013; 15(1):106-13.

66.Zaher H, Buters JT, Ward JM, Bruno MK, Lucas AM, Stern ST, Cohen SD, Gonzalez FJ. Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice. Toxicol. Appl. Pharmacol. 1998; 152:193–199.

67.Zhao Y, Geng CA, Ma YB, Huang XY, Chen H, Cao TW, He K, Wang H, Zhang XM, Chen JJ. UFLC/MS-IT-TOF guided isolation of anti-HBV active chlorogenic acid analogues from Artemisia capillaris as a traditional Chinese herb for the treatment of hepatitis. J Ethnopharmacol. 2014; 156:147-54。

Claims (38)

1. a kind of composition for treating liver and maintaining liver health comprising the mixture of plant extracts, wherein institute State plant extracts include at least one artemisia (Artemisia) extract, at least one Aloe (Aloe) gel powder and At least one Schizandra (Schizandra) extract.

2. a kind of composition for treating liver and maintaining liver health comprising the mixture of plant extracts, wherein institute Plant extracts is stated from the artemisia extract rich at least one polymer or biopolymer, is rich at least one chromone Aloe gel powder and Schizandra extract rich at least one lignan and organic acid.

3. composition according to claim 1, wherein the artemisia extract and Schizandra extract are with 4:1 to 1:4 Weight ratio be blended.

4. composition according to claim 1, wherein the Aloe gel powder is further with the weight of about 5% to about 50% Amount percentage is blended with the mixture of artemisia and Schizandra extract.

5. the mixture of composition according to claim 1, wherein artemisia, Schizandra and Aloe leaf gel powder Ratio is 8:4:3.

6. composition according to claim 2, wherein the artemisia extract includes 0.01% to 99.9% molecular weight height In 500 biopolymer.

7. composition according to claim 1, wherein the artemisia extract includes both A. absinthium (Artemisia ), absinthium the wooden wormwood artemisia (Artemisia abrotanum L.) in south, African wormwood artemisia (Artemisia afra), artemisia annua (Artemisia annua L), tree wormwood artemisia (Artemisia arborescens), Asia wormwood artemisia (Artemisia ), asiatica wilderness wormwood artemisia (Artemisia campestris), Artemisia deserti, Artemisia Iwayomogi, grey wormwood artemisia (Artemisia ludoviciana), north Chinese mugwort (Artemisia vulgaris), Artemisia Oelandica, stalwart wormwood artemisia (Artemisia princeps Pamp), white lotus wormwood artemisia (Artemisia sacrorum), artemisia scoparia (Artemisia scoparia), Artemisia stelleriana (Artemisia stelleriana), prairie sagewort (Artemisia frigida ), Willd Dillleaf Wormwood (Artemisia anethoides Mattf.), alkali wormwood artemisia (Artemisia anethifolia ), Weber. Artemisia faurier Nakai, wild marjoram (Origanum vulgare), siphonstegia chinensis (Siphenostegia chinensis) or any combination thereof.

8. composition according to claim 1, wherein the artemisia extract is selected from both A. absinthium (Artemisia ), absinthium the wooden wormwood artemisia (Artemisia abrotanum L.) in south, African wormwood artemisia (Artemisia afra), artemisia annua (Artemisia annua L), tree wormwood artemisia (Artemisia arborescens), Asia wormwood artemisia (Artemisia ), asiatica wilderness wormwood artemisia (Artemisia campestris), Artemisia deserti, Artemisia Iwayomogi, grey wormwood artemisia (Artemisia ludoviciana), north Chinese mugwort (Artemisia vulgaris), Artemisia Oelandica, stalwart wormwood artemisia (Artemisia princeps Pamp), white lotus wormwood artemisia (Artemisia sacrorum), artemisia scoparia (Artemisia scoparia), Artemisia stelleriana (Artemisia stelleriana), prairie sagewort (Artemisia frigida ), Willd Dillleaf Wormwood (Artemisia anethoides Mattf.), alkali wormwood artemisia (Artemisia anethifolia ), Weber. Artemisia faurier Nakai, wild marjoram (Origanum vulgare), siphonstegia chinensis (Siphenostegia chinensis) or any combination thereof.

9. composition according to claim 2, wherein one or more biopolymers be with water, methanol, ethyl alcohol, What alcohol, water mixed solvent or combinations thereof were extracted from sagebruss.

10. composition according to claim 1, wherein the Aloe gel powder includes aloe (Aloe ), arborescens aloe barbadensis Miller (Aloe barbadensis), Aloe cremnophila, Aloe ferox Miller (Aloe ), ferox A.saponaria (Aloe saponaria), aloe vera (Aloe vera), the Chinese aloe aloe (Aloe vera var. Chinensis) or combinations thereof.

11. composition according to claim 2, wherein at least one chromone compositions include about 0.01% to about 100% one or more chromones.

12. composition according to claim 2, wherein at least one chromone is selected from Aloesin (aloesin), Aloesinol, aloe A, aloe B, aloe C, aloe D, aloe E or any combination thereof.

13. composition according to claim 2, wherein the chromone compositions include the Aloesin of about 1% to about 4%, The wherein described composition is substantially free of anthraquinone and the wherein described aloe gel is from the plant selected from aloe barbadensis Miller or aloe vera Separation；And wherein described at least one chromone from aloe vera or Aloe ferox Miller or any combination thereof in separation.

14. composition according to claim 1, wherein the Schizandra includes Schisandra chinensis (Schisandra ), chinensis Schisandra elongate, Schisandra glabra, Kingsoft Schisandra chinensis (Schisandra ), glaucescens schisandra henryi Clarke (Schisandra henryi), Schisandra incarnate, narrow leaf Schisandra chinensis (Schisandra lancifolia), nepal magnoliavine fruit (Schisandra neglecta), Schisandra nigra, Close stamen Schisandra chinensis (Schisandra propinqua), nerville Schisandra chinensis (Schisandra pubescens), the two color five tastes Sub (Schisandra repanda), Schisandra sphnanthera (Schisandra rubriflora), Schisandra Rubrifolia, Schisandra sinensis, ball stamen Schisandra chinensis (Schisandra sphaerandra), Central China five tastes Sub (Schisandra sphenanthera), pubescence Schisandra chinensis (Schisandra tomentella), tumor branch Schisandra chinensis (Schisandra tuberculata), hair leaf Schisandra chinensis (Schisandra vestita), Schisandra viridis (Schisandra viridis), Heqing Schisandra chinensis (Schisandra wilsoniana) or combinations thereof.

15. composition according to claim 2, wherein at least one isolated from Schizandra extract Lignan is schizandrin, deoxidation schizandrin, wuweizisu B, puppet-wuweizisu B, wuweizisu B, the five tastes Sub- element C, isoschizandrin, Pregomisin, eoschizandrin, schisandrol, wuweizi alcohol A, wuweizi alcohol B, Schisantherin A, B, C, D, E, rubschisantherin, schisanhenol acetate (Schisanhenol acetdte), five Taste phenol B, schisanhenol, gomisin A, B, C, D, E, F, G, H, J, N, O, R, S, T, U, Biao Ge meter Pungent O, Radix Angelicae Sinensis acyl gomisin H, O, Q, T, igloylgomisin H, P, the different Gomisin O of Radix Angelicae Sinensis acyl, benzoyl-dagger-axe Rice pungent H, O, P, Q, different Ge meter Xin of benzoyl-or combinations thereof.

16. composition according to claim 2, wherein at least one isolated from Schizandra extract has Machine acid includes malic acid, citric acid, shikimic acid or combinations thereof.

17. composition according to claim 1, wherein the plant extract source is at least one plant selected from the following Object part：Stem, stem skin, trunk, trunk barks, branch, stem tuber, root, root skin, spray, seed, rhizome, flower and other genitals Official, leaf, other gas first portions or combinations thereof.

18. composition according to claim 2, wherein the plant extract source is at least one plant selected from the following Object part：Stem, stem skin, trunk, trunk barks, branch, stem tuber, root, root skin, spray, seed, rhizome, flower and other genitals Official, leaf, other gas first portions or combinations thereof.

19. composition according to claim 1, wherein the composition additionally comprises at least one hepatoprotective.

20. composition according to claim 2, wherein the composition additionally comprises at least one hepatoprotective.

21. composition according to claim 19, wherein the hepatoprotective include Milk Thistle, turmeric, radix bupleuri, Radix Glycyrrhizae, Salvia japonica, mulberry, Zhi Ji, hairyvein agrimony, cudrania cochinchinensis, lyceum, citrus, Lee, yellow plum, Korea gim, dandelion, grape, grape pip, Raspberry, camellia, green tea, krill oil, yeast, soybean plant powder or plant extracts；The silymarin of separation and enrichment, Flavonoids, phosphatide, thios, pycnogenol, gelatin, soybean lecithin, pancreatin；Natural or synthetic N-acetylcystein, ox sulphur Acid, riboflavin, niacin, pyridoxol, folic acid, carrotene, vitamin A, vitamin B2, B6, B16, vitamin C, vitamin E, paddy The sweet peptide of Guang, branched-chain amino acid, selenium, copper, zinc, manganese, Co-Q10, L-arginine, L-Glutamine, phosphatidyl choline or combinations thereof.

22. composition according to claim 20, wherein the hepatoprotective include Milk Thistle, turmeric, radix bupleuri, Radix Glycyrrhizae, Salvia japonica, mulberry, Zhi Ji, hairyvein agrimony, cudrania cochinchinensis, lyceum, citrus, Lee, yellow plum, Korea gim, dandelion, grape, grape pip, Raspberry, camellia, green tea, krill oil, yeast, soybean plant powder or plant extracts；The silymarin of separation and enrichment, Flavonoids, phosphatide, thios, pycnogenol, gelatin, soybean lecithin, pancreatin；Natural or synthetic N-acetylcystein, ox sulphur Acid, riboflavin, niacin, pyridoxol, folic acid, carrotene, vitamin A, vitamin B2, B6, B16, vitamin C, vitamin E, paddy The sweet peptide of Guang, branched-chain amino acid, selenium, copper, zinc, manganese, Co-Q10, L-arginine, L-Glutamine, phosphatidyl choline or combinations thereof.

23. composition according to claim 1, wherein the composition also includes acceptable load pharmaceutically or in health care Body, diluent or excipient.

24. composition according to claim 2, wherein the composition also includes acceptable load pharmaceutically or in health care Body, diluent or excipient.

25. composition according to claim 1, wherein the composition includes about 0.5 weight percent (wt%) to about 90 The active constituent of the mixture of the plant extracts of weight %.

26. composition according to claim 2, wherein the composition includes about 0.5 weight percent (wt%) to about 90 The active constituent of the mixture of the plant extracts of weight %.

27. composition according to claim 25, wherein the composition is formulated into tablet, hard capsule, soft gel glue Capsule, powder, particle, liquid, tincture, sashay, instant beverage single dose or pastille.

28. composition according to claim 26, wherein the composition is formulated into tablet, hard capsule, soft gel glue Capsule, powder, particle, liquid, tincture, sashay, instant beverage single dose or pastille.

29. composition according to claim 1, wherein the composition is with 0.01 to 500mg/kg the weight of animals dosage It gives.

30. composition according to claim 2, wherein the composition is with 0.01 to 500mg/kg the weight of animals dosage It gives.

31. one kind maintaining liver function for mammal, hepatocellular injury is made to minimize, promotes healthy liver, protection liver anti- Integrality is aoxidized, is neutralized a toxin, the Free Radical for influencing liver health is reduced, Scavenger of ROS species reduce oxidative stress, It prevents toxic metabolite from being formed, improves liver detoxification ability and/or function, clear liver, restore liver structure, protection liver cell is with gas defence Element helps liver blood flowing and cycle, supports liver function, enhance and liver of releiving, calms down and take a tonic or nourishing food to build up one's health liver, alleviates liver pain Bitterly, harmful chemical substance and organism are removed, supports the metabolic process of liver, mitigates liver discomfort, mitigates fatty liver, improve Liver detoxification ability reduces liver enzyme, provides native oxidant, increases SOD, increases GSH, reduces liver cell peroxidating, reduces fat Fat acid accumulation, the antiinflammatory processes kept fit improve liver immune function, promote liver cell regeneration, improve liver and update work( Can, stimulation bile discharges, and healthy bile flow, liver is promoted to restore, for overnutrition, overworked, excessive drinking, excessively The liver-protective pharmaceutical composition such as aging, wherein described pharmaceutical composition contain the composition of claim 1 as effectively at Point.

32. one kind maintaining liver function for mammal, hepatocellular injury is made to minimize, promotes healthy liver, protection liver anti- Integrality is aoxidized, is neutralized a toxin, the Free Radical for influencing liver health is reduced, Scavenger of ROS species reduce oxidative stress, It prevents toxic metabolite from being formed, improves liver detoxification ability and/or function, clear liver, restore liver structure, protection liver cell is with gas defence Element helps liver blood flowing and cycle, supports liver function, enhance and liver of releiving, calms down and take a tonic or nourishing food to build up one's health liver, alleviates liver pain Bitterly, harmful chemical substance and organism are removed, supports the metabolic process of liver, mitigates liver discomfort, mitigates fatty liver, improve Liver detoxification ability reduces liver enzyme, provides native oxidant, increases SOD, increases GSH, reduces liver cell peroxidating, reduces fat Fat acid accumulation, the antiinflammatory processes kept fit improve liver immune function, promote liver cell regeneration, improve liver and update work( Can, stimulation bile discharges, and healthy bile flow, liver is promoted to restore, for overnutrition, overworked, excessive drinking, excessively The liver-protective pharmaceutical composition such as aging, wherein described pharmaceutical composition contain the composition of claim 2 as effectively at Point.

33. pharmaceutical composition according to claim 31, wherein liver disorders or disease are virus hepatitis, alcoholic liver Inflammation, oneself immunity hepatitis, alcohol hepatopathy, fatty liver, steatosis, steatohepatitis, non-alcoholic fatty liver disease, drug Caused liver diseases, hardening, fibrosis, hepatic failure, drug-induced hepatic failure, metabolic syndrome, hepatocellular carcinoma, bile duct Cancer, primary biliary cirrhosis, bile capillaries, gilbert spy's syndrome, jaundice or any other hepatotoxicity correlation indication, And usually there is acceptable toxicity or any other liver correlation indication to patient, or any combination thereof.

34. pharmaceutical composition according to claim 32, wherein liver disorders or disease are virus hepatitis, alcoholic liver Inflammation, oneself immunity hepatitis, alcohol hepatopathy, fatty liver, steatosis, steatohepatitis, non-alcoholic fatty liver disease, drug Caused liver diseases, hardening, fibrosis, hepatic failure, drug-induced hepatic failure, metabolic syndrome, hepatocellular carcinoma, bile duct Cancer, primary biliary cirrhosis, bile capillaries, gilbert spy's syndrome, jaundice or any other hepatotoxicity correlation indication, And usually there is acceptable toxicity or any other liver correlation indication to patient, or any combination thereof.

35. one kind maintaining liver function for mammal, hepatocellular injury is made to minimize, promotes healthy liver, protection liver anti- Integrality is aoxidized, is neutralized a toxin, the Free Radical for influencing liver health is reduced, Scavenger of ROS species reduce oxidative stress, It prevents toxic metabolite from being formed, improves liver detoxification ability and/or function, clear liver, restore liver structure, protection liver cell is with gas defence Element helps liver blood flowing and cycle, supports liver function, enhance and liver of releiving, calms down and take a tonic or nourishing food to build up one's health liver, alleviates liver pain Bitterly, harmful chemical substance and organism are removed, supports the metabolic process of liver, mitigates liver discomfort, mitigates fatty liver, improve Liver detoxification ability reduces liver enzyme, provides native oxidant, increases SOD, increases GSH, reduces liver cell peroxidating, reduces fat Fat acid accumulation, the antiinflammatory processes kept fit improve liver immune function, promote liver cell regeneration, improve liver and update work( Can, stimulation bile discharges, and healthy bile flow, liver is promoted to restore, for overnutrition, overworked, excessive drinking, excessively The liver-protective method such as aging, including give the composition of a effective amount of claim 1.

36. one kind maintaining liver function for mammal, hepatocellular injury is made to minimize, promotes healthy liver, protection liver anti- Integrality is aoxidized, is neutralized a toxin, the Free Radical for influencing liver health is reduced, Scavenger of ROS species reduce oxidative stress, It prevents toxic metabolite from being formed, improves liver detoxification ability and/or function, clear liver, restore liver structure, protection liver cell is with gas defence Element helps liver blood flowing and cycle, supports liver function, enhance and liver of releiving, calms down and take a tonic or nourishing food to build up one's health liver, alleviates liver pain Bitterly, harmful chemical substance and organism are removed, supports the metabolic process of liver, mitigates liver discomfort, mitigates fatty liver, improve Liver detoxification ability reduces liver enzyme, provides native oxidant, increases SOD, increases GSH, reduces liver cell peroxidating, reduces fat Fat acid accumulation, the antiinflammatory processes kept fit improve liver immune function, promote liver cell regeneration, improve liver and update work( Can, stimulation bile discharges, and healthy bile flow, liver is promoted to restore, for overnutrition, overworked, excessive drinking, excessively The liver-protective method such as aging, including give the composition of a effective amount of claim 2.

37. the method according to claim 11, wherein liver disorders or disease are virus hepatitis, alcoholic hepatitis, from Body autoallergic, alcohol hepatopathy, fatty liver, steatosis, steatohepatitis, non-alcoholic fatty liver disease, drug cause Liver diseases, hardening, fibrosis, hepatic failure, drug-induced hepatic failure, metabolic syndrome, hepatocellular carcinoma, cholangiocarcinoma is former The biliary cirrhosis of hair property, bile capillaries, gilbert spy's syndrome, jaundice or any other hepatotoxicity correlation indication, and Usually there is acceptable toxicity or any other liver correlation indication to patient, or any combination thereof.

38. the method according to claim 11, wherein liver disorders or disease are virus hepatitis, alcoholic hepatitis, from Body autoallergic, alcohol hepatopathy, fatty liver, steatosis, steatohepatitis, non-alcoholic fatty liver disease, drug cause Liver diseases, hardening, fibrosis, hepatic failure, drug-induced hepatic failure, metabolic syndrome, hepatocellular carcinoma, cholangiocarcinoma is former The biliary cirrhosis of hair property, bile capillaries, gilbert spy's syndrome, jaundice or any other hepatotoxicity correlation indication, and Usually there is acceptable toxicity or any other liver correlation indication to patient, or any combination thereof.