WO2016159451A1 - Composition, for promoting ex vivo material degradation, containing n-, s- and p- and phellinus linteus extract or beta-glucan - Google Patents

Abstract

According to the present invention, beta-glucan (β-glucan) extracted and refined from Phellinus linteus (Phellinus species), yeast, barley or the like is confirmed to increase the expression of particularly FM03 among FM0 gene clusters in the liver and to promote the degradation of carbendazim which is a nitrogen-containing pesticide in a living matter. Therefore, the present invention can be utilized as a composition, for promoting ex vivo material degradation, containing N-, S- and P- and Phellinus linteus extract or beta-glucan.

Description

 【Specification】

 [Name of invention]

 N-. Containing situation mushroom extract or beta glucan as an active ingredient. S-. Composition for promoting degradation of P-containing exogenous substances

Technical Field

 The present invention is N-. Containing a species mushroom extract) or beta glucan (β -glucan) as an active ingredient. It relates to a composition for promoting the degradation of S-, P- containing xenobiotics.

Background Art

About 20, 000 species of mushrooms are known around the world, of which about 2,000 can be developed for food. There are about 992 species of mushrooms distributed in Korea, of which there are about 100 species of edible mushrooms, about 50 species of poisonous mushrooms, and about 20 species of poisonous mushrooms. More than 20 kinds of mushrooms can be grown in Korea, and anti-cancer, lowering cholesterol, and hypoglycemia have been proven. There are about 280 kinds of situation mushrooms worldwide. Most of the mushrooms are yellow and grow in rings. It is one of the most widely grown mushroom varieties. Mushrooms are known to have great potential as many ingredients in the production of useful bioactive metabolites and as medicines. The most common ¾e ////? "S species is woody mud, which is known as the Phellinus li eus, but in Korea, the most common cultivar is the Shampoo Baumi (/ ¾e ////? 7s baumin). It is known that Korea is the only place where S. mushroom Bumi is allowed for food and used as a health-promoting food. In addition to the fruiting body, the mycelial activity and evaluation of the efficacy of the situational mushroom extracts have been reviewed. As a variety of physiological activities such as effects, anticancer activity, gastric ulcer relieving effect and anti-inflammatory effect, and beta secretase (β-secretase) inhibitory activity for the treatment of Alzheimer's disease have been reported, many studies have been concentrated on the mycelial culture of mushrooms. However, the effect of promoting degradation of xenobiotics such as nicotine or pesticides of situation mushrooms or substances separated therefrom is not known. Beta-glucan is a bacterium or mushroom. Known as immune modulators obtained from yeast and grain sources. Generate polysaccharides. These glucose polymers are components of certain pathogenic bacteria and fungi cell walls. Beta-glucans consist of beta-1.3-linked beta-D-glucopyranosyl units regardless of the beta-1,6-associated side chains and preserve fungal cell wall components and. It is known to be recognized as one of the major PAMPs (Brown, 2006).

Long ago, higher fungi of basidiomycetes have been used as common medicines. The medicinal effects such as the immune-boosting and anti-tumor activity of mushrooms are believed to be due to betaglucan. Because _. Alphaglucan is a eukaryotic nutrient component, readily degraded to mammalian enzymes, and lacks immunostimulatory activity, while betaglucan is derived from various fungi and is not degraded by human enzymes when administered orally, but instead mucosal and systemic immunity in the small intestine Is stimulated and absorbed (Vos et al., 2007). Absorbed betaglucan is not only antitumor activity. Activates the ability to protect the host in the presence of fungi and bacteria in animals and humans. Beta-glucans are absorbed by the intestine, despite their high molecular weight. Activates innate and acquired immunity

Beta-glucans are glucose polymers, in which the backbone is a linear beta (1,3) -linked D-glucose molecule and various sizes of beta (1.6) -associated linkages at different intervals from the backbone. Variety of beta (1,3), beta (1.4) and beta (1,6) betaglucans—Only in association, only beta (1,3) activates immunity and shows antitumor activity. The first known function of betaglucan is antitumor activity (Chihara et al .. 1970), and then antifungal, anti-infective (ant i-infect ion Konddonk et al., 1992), radioprotective (Gu et al., 2005), reducing cholesterol (cholesterol Many other biological activities have been reported, including reduct ion (Wolever et al., 2011) and postprandial glucose metabolic act ivi ies (Batt i lana et al., 2001). Beta-glucans are known to affect Aspergillus (KTorosantucci et al., 2005) and Candida vaginal (Pietrel la et al .. 2010) infection in animals and Vibrio infection in sea fish (Zhu et al. , 2006) as a vaccine or adjuvant candidate for immunopotentiating activity. Beta-glucans of plants such as oats and barley are mainly beta (1,4) linked, and beta-glucans from mushrooms and fungi have branches with short beta (1.6) —associated sidechains in the beta (1,3) backbone (Yan et al. 2005). It is known that differences in the structure, form and source of glucans can affect biological activity (Brown and Gordon, 2001).

FMCKFlavin 一 containing monooxygenase is a group of enzymes that promote the oxidation of substrates primarily as nucleophiles through the cofactor, flavin. In contrast to the cytochrome P450 enzymes, FM0 is generally not induced or inhibited by xenobiotic substances. Human FM0 shows tissue characteristics, FM01 is present in human fetal liver and adult kidney, FM02 is in lung, and FM03 is present in adult.

 FM0 is the second group of microsomal oxidative enzymes with broad and overlapping specificities. The main reaction of FM0 is ni trogen, sulfur or phosphorus, in which the type of hetero-atom is N-oxide, S-oxide or P-oxide, respectively. Promote nucleophilicity of heteroatomic compounds. Although functional parts overlap with cytochrome P450, the mechanism of action is different. FM0 binds to and activates molecular oxygen before the substrate binds to the enzyme. It also requires a flavin adenosine dinucleotide (FAD) as a cofactor. Unlike the cytochrome P450 enzymes, FM0 is heat sensitive and can be used by researchers studying metabolism to distinguish enzyme systems.

FM03 contains a variety of N-, S- and P- It is known to metabolize and decompose xenobiotics, and such bioexotics include nicotine, pesticides and non-steroidal anti-inflammatory agents.

 Specifically, in smokers, nicotine is absorbed after the brain (accumulates up to 8% of the dose after 5 minutes of administration), kidneys (accumulates more than 14% of the dose), gastric mucosa, adrenal medulla, nasal mucosa and salivary glands Is concentrated on. In addition, nicotine accumulated in the body is a cancer disease, hypertension. It can cause various gastrointestinal diseases and arteriosclerosis caused by oral disease, promotion of gastric hypersecretion, and various circulatory diseases including arteriosclerosis. cause. These nicotine is broken down into nicotine-1-N-oxide by FM03, and most of it is known to be excreted in the urine as it is. In addition, pesticides are harmful to crops, germs. Drugs that remove weeds or grow crops include pesticides, fungicides, stimulants and growth promoters. Pesticides sprayed on crops are easily absorbed by the person or animal that consumed the crops and accumulate in the body. Pesticides come in many varieties, including atrazine, alaclo and carbendazime. Atrazine (Atrazine) is an s-triazine-type transitional non-hormonal herbicide having the structure of Formula 1, and the main herbicide is considered to inhibit photosynthesis. Used for In corn resistant to atrazine, a mechanism for inactivating the atrazine second-place chlorine by replacing it with S-glutathione is known. In addition, most of the plants or resistance variants that have acquired resistance are mutated from the chloroplast D-1 protein, which is the target protein of atrazine. These mutant genes are introduced to produce atrazine resistant plants.

 Formula 11

알라클로 (Al achlor )는 하기 화학식 2의 구조로 옥수수, 콩， 감자 등의 경작에 사용되는 제초제로서 토양에 방출되면 광분해와 미생물에 의한 분해가 빨리 진행되나, 인체에 축적될 경우 염색체 이상 및 위장, 갑상선, 비장 등에서 암을 유발한다고 알려져있다.

Al achlor is a herbicide used in the cultivation of corn, soybeans, potatoes, etc. with the structure of Chemical Formula 2, and when released to soil, photolysis and decomposition by microorganisms are accelerated. It is known to cause cancer in the thyroid gland, spleen, etc.

 2】

 Carbendazini was evaluated in 1973 for its residue and again in 1994 (res idues) and 1995 (toxicology and environment). The CCPR (Residual Pesticides Division) requires a risk assessment and recommends reconsidering the definition of residues based on information specified by the UK (ALIN0RM 97/24. Para 51). The UK expressed the residual definition of the sum of thiophanate-methyl, benomyl and carbendazim expressed in carbendazim. Maximum residue limits (MRLs) include carbendazim residues that occur either directly or as metabolites. Data was provided by major manufacturers and the Dutch government. Carbendazim has the structure of Formula 1, is called carbendazim in ISO, chemically IUPAC is called Methyl benzimidazol— 2-ylcarbamate, CA is called Methyl ΙΗ-benz i πι idazol-2-yl carbamate, CAS The number is 10605-21-7.

 [Formula 3]

Nonsteroidal anti-inflammatory drugs (non-s teroi dal ant i-inf l ammatorydrugs, NSAIDs) are nonnarcotic with anti-inflammatory, analgesic and antipyretic effects. It is a nonsteroidal agent. It is known to damage liver, kidney, hearing, etc. due to side effects caused by the administration and accumulation of these NSAIDs.

 Benzydamin (Benzydaniine) is a nonsteroidal anti-inflammatory drug which acts locally with the structure of Formula 4, and can be used for the treatment of local anesthesia in the mouth and throat, analgesic for pain relief, and anti-inflammatory treatment in inflammatory conditions.

 [Formula 4]

 Non-steroidal anti-inflammatory drugs similar to benzidamine include methyl p-tolyl sulfide (MTS) of formula (5), and sulindac sulfide of formula (6).

이에, 본 발명자들은 상기 문제점을 해결하기 위해 연구한 결과. FM03 유전자 발현이 증가하면 체내 니코틴 또는 농약과 같은 N-. S-. P-를 함유하는 생체외래물질의 분해가 촉진됨을 확인하였고 상황버섯 추출물 및 상황버섯에서 분리한 베타글루칸을 동물 모델에 경구투여할 경우, 간에서 FM03의 발현이 현저히 증가하며， 카벤다짐의 분해를 촉진시키는 것을 확인함으로써, 상황버섯 추출물 및 베타글루칸을 N-, S-, P-를 함유하는 생체외래물질 분해 촉진용 조성물로 유용하게 사용할 수 있음을 밝힘으로써 본 발명을 완성하였다. [Formula 5]

Thus, the present inventors studied to solve the above problems. Increasing FM03 gene expression results in N-. S-. It was confirmed that the degradation of P- containing exogenous substances was promoted. When oral administration of the gluco mushroom extract and beta glucan isolated from the mushrooms to the animal model significantly increased the expression of FM03 in the liver. By confirming to promote, the present invention was completed by revealing that the mushroom extract and beta glucan can be usefully used as a composition for promoting the degradation of foreign substances containing N-, S- and P-.

[Detailed Description of the Invention]

 [Technical problem]

 An object of the present invention is to promote the degradation of xenobiotics containing N-, S-, P- containing ¾e //// s species extract or beta-glucan as an active ingredient. It is to provide a composition for.

 It is still another object of the present invention to provide a N-, S-, P-containing xenobiotics degradation accelerator which contains an extract of a situation mushroom (/ ¾e //// "s species) or beta glucan as an active ingredient. will be.

 Still another object of the present invention is to provide a method for promoting degradation of N-, S-, P-containing xenobiotics, which contains an extract of a situation mushroom (/ ¾e //// 7 "s species) or beta glucan as an active ingredient. To provide.

Technical Solution

 To achieve the above object. The present invention provides a composition for promoting degradation of N-, S-, P-containing xenobiotics, which contains an extract of a situation mushroom (/ e //// s species) as an active ingredient.

In addition, the present invention provides a N-, S-, P-containing xenobiotics degradation accelerator containing a situation mushroom (/ ¾e //// 7i / s species) extract as an active ingredient. Also. The present invention provides a dietary supplement for promoting the degradation of N-, S-.P- containing xenobiotics containing an extract of ¾e /// 2/2 species species as an active ingredient. In addition, the present invention provides a feed additive for promoting degradation of N-, S-, P-containing xenobiotics, which contains an extract of a situation mushroom (/ ¾e ////? I / s species) as an active ingredient. .

 The present invention also provides a method for promoting degradation of N-, S-, P-containing exogenous substances, which comprises administering an extract of a situation mushroom (/ ¾e // s species) to an individual except a human.

 In addition, the present invention provides a mushroom extract (/ ¾e // ;; i / s species) extract or a composition containing the same as an active ingredient for use in promoting N-, S-, P-containing bio-exogenous decomposition.

 Also. The present invention N-, S-, containing beta glucan (β-glucan) as an active ingredient

Provided is a composition for promoting P-containing exogenous degradation.

 In addition, the present invention provides an N-, S-, P-containing exogenous biodegradation accelerator containing beta-glucan as an active ingredient.

 In addition, the present invention, N—, S-. Containing beta glucan (β-glucan) as an active ingredient. It provides a health functional food for promoting the degradation of P-containing exogenous foreign substances.

 Also. The present invention provides a feed additive for promoting the degradation of N-, S-, P-containing exogenous substances containing beta glucan (β-glucan) as an active ingredient.

 In addition, the present invention N-. Containing beta glucan (β- glucan) as an active ingredient. Provided is a method for promoting degradation of S- ， P- containing exogenous foreign substances.

 In addition, the present invention is N-, S-. It provides beta glucan (β-glucan) or a composition containing the same as an active ingredient for use in promoting P-containing exogenous degradation.

Advantageous Effects

By confirming that the situation mushroom (/ ¾e //// 77s species) extract or betaglucan (β-glucan) of the present invention increases the expression of FM03, especially in the FM0 gene group in the liver, and promotes the decomposition of carbendazim, The situation mushroom extract or beta glucan can be usefully used as a composition for promoting degradation of xenobiotics containing N-, S-, P—. [Brief Description of Drawings]

 La is a histogram showing the results of analysis of hepatic gene expression changes in the situation mushroom spec ies) hydrothermal extract (PBE) single administration group. FIG. Lb is a box plot showing the results of analysis of liver gene expression in the PBE single dose group.

 Figure lc is a diagram showing the results of analysis of hepatic gene expression changes in a PBE single administration group as a MA plot.

 FIG. Id is a diagram showing the results of analysis of liver gene expression in a PBE single dose group as a correlation analysis scatter plot.

 Figure 2a is a diagram showing the hierarchical clustering results in the situation mushroom hot water extract (PBE) single administration group.

 Figure 2b is a diagram showing the gene expression pattern in the situation mushroom hot water extract (PBE) single administration group.

 Figure 3a is a histogram showing the results of analyzing the changes in liver gene expression in the situation mushroom hot water extract (PBE) multi-administered group.

 Figure 3b is a box diagram showing the results of analyzing the changes in liver gene expression in the situation mushroom hot water extract (PBE) multi-administered group.

 Figure 3c is a diagram showing the results of analysis of hepatic gene expression changes in the PBE multi-administration group of situation mushrooms.

 Figure 3d is a diagram showing the results of analysis of the changes in liver gene expression in the situation mushroom hot water extract (PBE) multi-administration group.

 Figure 4a is a diagram showing the hierarchical clustering results in the situation mushroom hot water extract (PBE) multi-administration group.

 Figure 4b is a diagram showing the gene expression pattern in the situation mushroom hot water extract (PBE) multi-administration group.

 5 is a diagram confirming the RNA quality (qual i ty) in the situation mushroom hot water extract (PBE) administration group:

Cont: control; And PBE: Treated mushroom hot water extract group.

 6 is a diagram confirming the expression of FM0 (F 1 av i n-cont a n i ng monooxygenase) gene according to the mi "mouse tissue:

 Tissues: Type of Tissue;

 Liver: Liver Tissue;

 Lung: lung tissue; and

 Kidney; Kidney tissue.

 Figure 7 is a diagram confirming the change in expression of FM0 gene according to the mouse tissue-specific extract treatment.

 Tissues: tissue type;

 Liver ： Liver tissue;

 Lung: lung tissue;

 Kidney; Kidney tissue;

 Cont: control;

 PBE: Treated mushroom hot water extract group:

 PBW: situation mushroom aqueous fraction treatment group;

 PBG: situation mushroom beta glucan treated group;

 20: 20 mg / kg; And

 100: 100 mg / kg.

 8a to 8b is a diagram showing the results of high-performance liquid chromatography (HPLC) analysis after oral administration of carbendazim 1 mg / iii, (A) is a result showing the criteria of carbendazim , (B) is the result 30 minutes after oral administration. (C) is 1 hour after oral administration, (D) is 1.5 hours after oral administration, (E) is 2 hours after oral administration, (F) is 6 hours after oral administration, and (G ) Is 12 hours after oral administration.

9a to 9b is a diagram showing the results of HPLC analysis after oral administration of carbendazim 500 mg / kg after administration of 20 mg / kg of Pleurotus erythematosus (PBE) once a day for 7 days, (A ) Is 30 minutes after carbendazim oral administration, (B) is 1 hour after carbendazim oral administration, (C) is 1.5 hours after carbendazim oral administration, and (D) is The result is 2 hours after oral carbendazim, (E) is 6 hours after oral carbendazim, and (F) is 12 hours after oral carbendazim.

 10a to 10b is a diagram showing the results of HPLC analysis after orally administering 500 mg / kg of carbendazim after administering 100 nig / kg of Phellinaceae mushroom hot water extract (PBE) once a day for 7 days, (A ) Is 30 minutes after oral carbendazim, and (B) is 1 hour after oral carbendazim. (C) results after 1.5 hours of oral carbendazim, (D) results after 2 hours of oral carbendazim, (E) results after 6 hours of oral carbendazim, and (F) oral administration of carbendazim The result is 12 hours later.

 11 is a graph showing the results of analysis by HPLC.

 12 is a diagram showing the expression of FM03 by oral administration of various beta glucans in SD rats. PBG (25 mg / kg), Zymosan (25 mg / kg) and Barley (25 mg / kg) were orally administered to rats (n = 3) once a day for 7 days, and livers were extracted to express the expression of FM03. Analysis by time PCR:

 FM03: flavin containing monooxygenase 3;

 Con: control;

 PBG: Phellinus baumii β-D-glucan; And

Zymosan: β-D-glucan from yeast; Barley: ^' .β _D—glucan (pur i ty: ≥95%) from bar ley. [Best form for implementation of the invention]

 Hereinafter, the present invention will be described in detail. The present invention is N-. Containing a situation mushroom species extract or beta glucan (β- glucan) as an active ingredient. Provided is a composition for promoting degradation of S-, P-containing xenobiotics.

 The situation mushroom extract is preferably prepared by a manufacturing method including the following steps, but is not limited thereto.

 1) extracting by adding an extraction solvent to the situation mushroom;

2) cooling the extract of step 1) and then filtering; And 3) drying the filtered extract of step 2) under reduced pressure. In the above method, the extraction solvent of step 1) is preferably extracted with water, Ci to C ₂ lower alcohol or a mixture thereof as a solvent, and the lower alcohol is preferably ethanol or methanol, but is not limited thereto. It is not. The extraction solvent is preferably 10 to 100 times, preferably 20 to 50 times the dried situation mushroom, but is not limited thereto. The extraction temperature is preferably 70 to 140 ^° C, preferably 85 to 110 ° C, but is not limited thereto. In addition, the extraction time is preferably 1 to 36 hours, preferably 9 to 24 hours. It is not limited to this.

 In the above method, the decompression concentration in step 3) may be to use a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, the drying may be a vacuum drying, vacuum drying, rain drying, spray drying or freeze drying, but is not limited thereto.

The situation mushroom is preferably mushroom mushroom Baumi (/ ¾e /// s bau ii) or mushroom mushroom Linteus (A¾e /// s linteus) ⁰ A, and more preferably, mushroom mushroom Baumi.

 The beta glucan is preferably isolated from any one selected from the group consisting of basidiomycetes and fungi, Situation mushroom, Ganoderma lucidum (Ganoder lucidum). More preferably, it is isolated from any one selected from the group consisting of fungi, including basidiomycetes, such as Cordyceps, plants such as barley, and yeast, and more preferably, isolated from situation mushrooms, barley or yeast.

 The situation mushroom extract or beta glucan is characterized by increasing the expression of FM03 (Fl avin-cont i ng monooxygenase3) gene.

 The N-, S-, P-containing exogenous foreign substance is preferably at least one selected from the group consisting of nicotine, pesticides and pharmaceuticals accumulated in the body, more preferably nicotine or pesticides, but is not limited thereto. In addition, the drug may be a nonsteroidal anti-inflammatory agent.

The pesticide is preferably any one or more selected from the group consisting of pesticides, fungicides and herbicides. The FM03 gene has a nucleotide sequence represented by SEQ ID NO: 13 (GenBank Accession No .: NM—008030). In a specific embodiment of the present invention. The inventors of the situation mushroom hot water extract. Aqueous mushroom aqueous fraction and beta glucan were prepared and divided into single administration (24 hours) and multiple administration (7 days), and then orally administered once a day. The expression of liver genes in the single-dose and multi-dose groups was confirmed (see FIGS. La to 4b), and the changes in the expression of FM0 genes in mice treated with P. sessile mushroom hot water extract (PBE) were determined. FM03 gene expression was increased at both doses (see Table 4), and RA quality in tissues was visualized and confirmed (see FIG. 5).

 In addition, the inventors confirmed the expression of the FM0 gene according to the mouse tissue. Even in the same FM0 gene family, it was confirmed that there was a difference in expression levels according to tissues (see FIG. 6), the situation mushroom hot water extract (PBE), the situation mushroom water fraction (PBW), and the situation mushroom beta glucan (PBG) As a result of confirming the expression change of the FM0 gene in the tissue, it was confirmed that the expression level increased depending on the treatment concentration in FM03 in the liver and FM04 in the kidney (see FIG. 7).

 In addition, the present inventors, after the filtrate the fibrous mushroom hot water extract through high-performance liquid chromatography (HPLC) analysis, after confirming the decomposition of the pesticide by administering the carbendazim, the situation mushroom hot water extract than In addition, it was confirmed that the amount of carbendazim remaining in the mouse body decreases in proportion to the administered concentration of the situation mushroom hot water extract when the situation mushroom hot water extract was administered (see FIGS. 8A to 11).

 In addition, the present inventors orally administered Zymosan (yeast beta glucan) and Barley (barley beta glucan) for 7 days, and analyzed FM03 expressed in the liver of rats by real time PCR. As a result, it was confirmed that the increase of 2.4 times (2.43 土 0.34) 상황 in yeast beta glucan and 2.9 times (2.94 ± 0.19) in yeast beta glucan and 2.2 times (2.15 土 0.31) in barley beta glucan (see FIG. 12). ).

In conclusion, the increase of beta glucan-induced FM03 may be due to the It was also found to be not limited, but also by yeast and plant-derived barley betaglucan. In other words. The use of inexpensive yeast or barley beta glucan increases the expression of FM03 rather than using expensive mushrooms. The release of various exogenous substances (xenob i ot i cs) containing various N-, S- and P- absorbed into the body, such as residual pesticides and nicotine, can be effectively achieved by increased FM03.

 therefore. By confirming that the situation mushroom extract or betaglucan of the present invention increases the expression of FM03, especially in the FM0 gene group in the liver, and promotes the decomposition of carbendazim. The situation mushroom extract or beta glucan, it was confirmed that it can be usefully used as a composition for promoting the degradation of foreign substances containing N-, ᅳ S-, P-. Also. The present invention is N- containing a situation mushroom extract or beta glucan as an active ingredient. S-, P- containing bio-exogenous decomposition accelerators are provided.

 The situation mushroom extract or beta glucan of the present invention by confirming that in the liver increases the expression of FM03, especially in the FM0 gene group, and promotes the decomposition of carbendazim, the situation mushroom extract or beta glucan. N-, S-. It was confirmed that the present invention can be usefully used as a bio-degradation accelerator containing P-. Also. The present invention provides a health functional food for promoting degradation of N-, S-, P-containing bio-exogenous substances containing a situation mushroom extract or beta glucan as an active ingredient. The situation mushroom extract or betaglucan of the present invention increases the expression of FM03, particularly among the FM0 gene group in the liver. By confirming that it promotes the decomposition of carbendazim. The situation mushroom extract or beta glucan, N-, S-. It has been confirmed that it can be usefully used as a natural medicine or health functional food for promoting decomposition of exogenous substances containing P-.

The composition of the present invention having the effect of promoting degradation of exogenous substances containing N-, S-, and P- may include a situation mushroom extract or beta glucan alone or One or more pharmaceutically acceptable carriers. By further comprising an excipient or diluent, it may be formulated as a pharmaceutical composition by conventional methods.

 As used herein, "pharmaceutically acceptable" refers to a composition that is physiologically acceptable and does not cause allergic reactions or similar reactions, such as gastrointestinal disorders dizziness, when administered to humans. In addition, the pharmaceutical compositions of the present invention formulated as above may be formulated through N—, S-. It may be administered for the purpose of promoting degradation of exogenous substances containing P-. Suitable routes of administration may include several routes including oral, transdermal, subcutaneous, intravenous or intramuscular.

 In the pharmaceutical composition of the present invention, the pharmaceutical composition may be formulated into a formulation for oral administration or parenteral administration according to the selected route of administration, and when formulated, a layering agent, an extender, a binder, and a humectant which are usually used. Disintegrant. It is prepared using diluents or excipients such as surfactants. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carboate (Cal ci um carbonate) , Sucrose or lactose: It is prepared by mixing gelatin and the like. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, for example, wetting agents, sweeteners, fragrances, and preservatives, may be included. have. Formulations for parenteral administration include external skin preparations.

When the composition which provides the N-, S-, and P- containing composition of the present invention, which provides the effect of promoting degradation of exogenous foreign substances, is not particularly limited in its formulation, for example, lotion and ointment. Gel, cream. It may be prepared in the form of a patch or spray. In the pharmaceutical composition of the present invention, the situation mushroom extract or betaglucan is preferably included in an amount of 0.01 to 90% by weight based on the total weight of the pharmaceutical composition. However, the composition as described above is not necessarily limited _to, the patient's condition. It may vary depending on the type of disease and the degree of progression.

In the pharmaceutical composition of the present invention. The situation mushroom extract or The preferred dosage of betaglucan depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, it is recommended to administer at 0.001 mg / kg to 10 g / kg per day. Administration may be administered once a day, or may be administered several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect. The pharmaceutical composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes. All modes of anticipated administration are possible, for example oral, dermal application, rectal, or intravenous, muscle, subcutaneous. Administration may be by intrauterine dural or intravascular cerebrovascular injection. The pharmaceutical composition according to the present invention may be used alone or in combination with methods using surgery, hormonal therapy, drug treatment, and biological response modifiers to promote exogenous degradation of N-, S-, P-containing compounds. Can be.

In addition, the present invention provides a feed additive for promoting the degradation of S-, P- containing exogenous foreign substances containing a situation mushroom extract or beta glucan as an active ingredient.

It is preferable that the active ingredient of the present invention is composed of 0.01 to 10 parts by weight based on the feed to be added to the situation mushroom extract or beta glucan, but is not limited thereto. The feed additive composition of the present invention, in addition to the components described above for administration, in addition to organic acids such as citric acid, fumaric acid adipic acid, lactic acid, phosphates such as potassium phosphate, sodium phosphate, polymerized phosphate, polyphenols, catechin tocopherol, vitamin C , Green tea extract ᅳ chitosan. One or more components of natural antioxidants such as tannic acid can be used in combination, and anti-influenza preparations and buffers as necessary. Other conventional additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate injectable formulations _, capsules _, granules or tablets such as aqueous solutions and suspension emulsions.

In addition, the feed additive composition of the present invention and the feed composition comprising the same as amino acids, inorganic salts as auxiliary components. A variety of supplements such as vitamins, antioxidants, microbial preparations, and animal protein feeds such as pulverized or crushed vegetable protein feeds such as wheat, barley and corn, blood meal, meat meal and fish meal. Like animal fats and vegetable fats In addition to the main ingredients, nutritional supplements. Growth promoters can be used in conjunction with digestive absorption accelerators and disease prevention agents.

 The feed additive for animal feed can be easily administered directly or in combination with other ingredients by oral formulation, injection or transdermal alone or directly in the feed of the animal. Dosage ranges depending on the animal's weight, health status, diet, administration method and the severity of the disease. As is well known in the art, the daily dosage is about 0.1-10 nig / g, preferably 0.05-1 nig / g, and more preferably, once or several times a day.

 Feed additives of the present invention can be added to the feed for the purpose of odor reduction. When the feed additive of the present invention is used as a feed additive, the feed additive may be added as it is or used together with other ingredients and may be suitably used according to a conventional method. Dosage forms of feed additives may be prepared in immediate release or sustained release formulations in combination with non-toxic pharmaceutically acceptable carriers. Such edible carriers may be corn starch, lactose, sucrose and soybean plate propylene glycol. Tablets for solid carriers. It may be used as a powder, a toroki, and in the case of a liquid carrier, it may be a syrup, a liquid suspension, an emulsion, or a solution dosage form. Dosages may also contain preservatives, lubricants, solution promoters, stabilizers, and may contain other inflammatory disease ameliorating agents and substances useful for virus prevention.

 The feed additive composition of the present invention is applicable to a number of animal diets, ie feeds, including mammals, poultry, fish and shellfish. Commercially important pigs. It can be used for mammals, such as a cow and a goat, zoo animals, such as an elephant and a camel, and livestock, such as a dog and a cat. Chickens in poultry commercially critical. Ducks, geese, etc. may be included and may include commercially raised fish and crustaceans such as trout and shrimp.

Animal feed blending method comprising a feed additive composition according to the present invention is to mix the feed additive composition in animal feed in an amount of about 10g to 500g, preferably 10g to 100g per kg on a dry weight basis. You can also mix the feed mixture thoroughly and then feed it as a mash. Palletization, expansion, extrusion through the further processing process is preferred. _{Λ Q}

 lo also. The present invention comprises the step of administering a situation mushroom extract or beta glucan to a subject other than human. Provided is a method for promoting S- and P-containing exogenous degradation.

 Subjects except humans except humans. Sheep, pigs, goats, camels, antelopes. Cows, chickens. Duck, dog. Means animals such as cats.

 The N- ᅳ S- and P-containing methods for promoting biodegradation of exogenous substances, although not for humans, do not mean that these methods are ineffective in humans. In addition, in the case of humans, it can be sufficiently used for promoting the degradation of exogenous substances by the N-, S-, P-containing exogenous degradation acceleration method according to the present invention.

 The situation mushroom extract or betaglucan of the present invention increases the expression of FM03, especially in the FM0 genotype in the liver, and confirms that it promotes the decomposition of carbendazim, thereby making the situation mushroom extract or betaglucan N-, S-. It was confirmed that it can be usefully used as a method for promoting degradation of foreign substances containing P-. Hereinafter, the present invention will be described in detail by way of examples.

 However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples. Statistical processing

 The experimental results were expressed as the average standard deviation, and all measurements were performed at least three times. Intergroup comparison of mean values was performed by AN0VA unidirectional analysis using InStat 3.06 (GraphPad software Inc., USA). Significant p value is indicated as ≤0.05.

Example 1 Preparation of Extract of Situation Mushroom (/ ¾e //// H / s baimii)

 <1-1> Preparation of Situary Mushroom Hot Water Extract (/ ¾e /// 7i / s baimii extract, ΡΒΕ)

The present inventors in preparing the situation mushroom extract, the extraction yield is the temperature, the amount of purified water, PH. Depending on the extraction time and situation of extraction, such as mushroom pieces It confirmed that it became. Usually extraction temperature is 85 ^° C, 90 ^° C. 95 ^° C. 100 ^° C., 105 ^° C. and 110 ^° C., extraction times are 9 hours, 18 hours and 24 hours. Thus, the dried mushrooms were dried to pieces, and purified water 200 (20 or 50 times) was added to 4 g or 10 g of the mushroom pieces, and the suspension was filtered, and the extraction yield was measured.

 In addition, the extract was mass-produced using the above method. The pulverized mushroom mushroom pieces and 20 ί purified water were added to a 200 ί extractor and extracted 20 times at 1 C for 24 hours. After filtration through a filter unit. The filtrate was concentrated. It was lyophilized under reduced pressure, respectively. Extraction yield is shown in Table 1 below.

Table 11

 In this study, the situation mushroom hot water extract was prepared by purchasing the situation mushroom fruiting bodies grown in Korea.

Specifically, loo g of the fruiting body fruit loo g was put into distilled water of 2000 and extracted with a hot bath of ioo ° c for 24 hours. After filtering and storing the extract, add 2000 m of distilled water to the residue, extract for 24 hours with 100 ^° C bath, and extract it three times. The extract was concentrated under reduced pressure to 100 ι, and then lyophilized. / ¾e ////? "S bauwii ext ract, PBE).

<1-2> Preparation of S. mushroom extracts (/ ¾e //// M / s bauwii water fract ion, PB) and S. mushroom beta glucan (/ ¾e /// K s baumii β-Glucan, PBG)

 Purified beta glucan using a well-known method to purchase the situation mushroom fruiting body grown in Korea.

Specifically. 100 g of situation fruiting body was added to 2000 me of distilled water, and extracted with 100 ^° C. hot water for 24 hours. After filtering and storing the extract, add 2000 distilled water to the residue, extract it for 24 hours with 100 ^° C bath, and extract it three times. The extract was concentrated to 100 ^° C and concentrated to 4 ^° C. To the concentrate was added 300 inC ethane (about 3 times) ice-cooled to -20 ^° C. and placed at 4 ^° C. for 4 hours After 4 hours, the precipitate was beta glucan and the isolated beta glucan was Bet a-gl ucan. assay It was confirmed using the kit (Megazyme.co). It was lyophilized to be called circumference mushroom beta glucan baumii β-Glucan (PBG). On the other hand, the supernatant which does not precipitate ethane in the situation mushroom hot water extract was filtered through filter paper, concentrated and then lyophilized to be called situation mushroom water layer fraction (/ ¾e /// y? I / s baumii water fraction.PBW). .

Example 2 Cell Culture and Animal Model Design

 <2-1> cell culture

Raw 264.7 cells (ATCC, Rockville, MD), a mouse macrophage line, were penicillin (10,000 units / mO-streptoinycin) (10,000 Linits / ni and Fetal Bovine Serum, FBS) (Gibco -BRL, USA) was subcultured with DMEM medium and incubated in a 37 ° C., 5% C0 ₂ incubator, incubated in a T-25 flask and 10 × Trypsin-EDTA when subcultured. The solution was diluted 10-fold with DMEM and used to mix IX trypsin-EDTA solution in Raw 264.7 cells cultured in a tissue culture flask at 37 ^° C for 10 minutes, and then make single cells by trypsin reaction. To terminate this reaction, DMEM medium containing 1 FBS was added followed by two washes, followed by subculture at low grams and subculture.

 Five-week-old male MPF (murine pathogen free, outbred-mouse) ICR mice weighing 25-30 g were purchased from Samtako Bio Korea and used as oral administration experimental animals. Mice were allowed to eat freely of water and diet and set the lighting cycle to 12 hours bright and 12 hours dark. The room was kept at 22.5 ° C. and 42.5% humidity.

The situation mushroom hot water extract was dissolved in distilled water using lyophilized powder and orally administered. The experimental group was divided into a control group (control. N = 2), 100 nig / kg of water-soluble physiological mushroom hot water extract treatment group (PBE-100, n = 2), and a single dose (24 hours) and multiple doses (7 days). The doses were administered orally once a day. Also. Green mushroom extract (PBE), green mushroom extract (PBW) and green mushroom beta glucan (PBG) were lyophilized and dissolved in distilled water. The experimental group was the control group (control, n = 3), 20 mg / kg of situation mushroom hot water extract treatment group (PBE-20, n = 3), 100 mg / kg of situation mushroom hot water extract treatment group (PBE-100. N = 3). 20 nig / kg of pruning mushroom water fraction (PBW-20, n = 3). 100 nig / kg of Phellinus aureus fraction (PBW, 100, n = 3), 20 nig / kg of Phellinus betaglucan treated group (PBG-20, n = 3) and 100 mg / kg of Phellinum Mushroom Beta The glucan treatment group (PBG-100, n = 3) was divided and administered orally once a day for 7 days. <2-3> Pesticide oral administration animal model

 Carbodazim (Methyl benzimidazol—2yl carbamate BCM, Methyl 2benzimidazolecarbamate) suspended in rurib oil after oral administration of S. mushroom extract (PBE) or betaglucan 20 and 100 nig / kg once a day for 7 days C9H9N302, FW 191.19) (Sigma Aldrich Chemical) 500 mg / kg, and a control group was administered a carbendazim 500 uig / kg to a single gavage.

Example 3 Analysis of Changes in Liver Gene Expression in Single-dose Groups

^"Samples taken from the animal model designed in the same manner as in Example <2-2> were obtained the expression of genes through the liver microarrays (niicroarray) method.

Specifically, single-dose group mice were euthanized with dichloromethan (CH ₂ C1 ₂ ) among animal models designed in the same manner as in Example <2-2> to obtain 150 nig tissue in a 2 mi tube, and RNA was obtained. Samples were stored below -20 ° C to obtain. Microarrays were performed using a Mouse Gene 1.0 ST array (Af fymetr ix Inc) to identify 0D 260/280. The results were analyzed using histogram, box plot, MA plot, and correlation scatter plot.

As a result, as shown in la to FIG. It was confirmed (FIG. La to Id).

 In addition, based on the results of the analysis of the main genes compared to the control group in the experimental group in a single oral administration of the situation mushroom hot water extract (PBE) at a concentration of 100 mg / kg is shown in Table 2 below.

 Table 2

 In addition, cutof f 2.0 was set based on Table 2, and specific gene clustering was performed using hierarchical clustering.

 As a result, as shown in Figures 2a and 2b, the hierarchical clustering results of the control group and the situation mushroom hot water extract treatment group was confirmed. Its gene expression pattern was confirmed (FIGS. 2A and 2B).

Example 4 Analysis of Changes in Liver Gene Expression in Multi-dose Groups

 Liver samples were taken from the liver with animal models designed in the same manner as in Example <2-2>, and the expression changes of liver genes were analyzed by a microarray method.

 Specifically, a multi-dose group mouse among animal models designed in the same manner as in Example <2-2> was analyzed in the same manner as in <Example 3>. As a result, as shown in FIGS. 3A to 3D. Liver gene expression patterns were confirmed (FIGS. 3A-3D).

In addition, the main genes were analyzed based on the results, and compared to the control group, the situation mushroom hot water extract (PBE) was administered orally at a concentration of 100 mg / kg for 7 days. Changes in expression patterns in the experimental group are shown in Table 3 below.

또한, 상기 <표 3>를 바탕으로 cutof f 2.0으로 설정하여, 계층적 클러스터링 (c luster ing)을 이용하여 특정 유전자 클러스터링을 수행하였다. Table 3

In addition, cutof f 2.0 was set based on Table 3, and specific gene clustering was performed using hierarchical clustering.

 As a result, as shown in Figures 4a and 4b, the results of the hierarchical clustering of the control group and the situation mushroom hot water extract treatment group was confirmed, its gene expression pattern was confirmed (Figs. 4a and 4b).

Example 5 Confirmation of Expression Change of FMKFlavin-containing Monooxygenase Gene

 Changes in the expression of FM0 gene in hepatic tissue (liver t i ssue) of ICR mice orally administered with PBE were obtained using the same method as in <Example 3>.

 Table 4

As shown in Table 4 above. FM03 for single dose Only genes were increased by 5.13 fold, and FM02 was 3.8 fold in case of multiple doses. It was confirmed that FM03 increased by 17.6 times and FM04 increased by 3.14 times (Table 4).

Example 6 RNA Quality

 RNA was obtained from the tissue obtained in the same manner as in <Example 3> and confirmed by visualizing 18S ribosomal RNA (rRNA) and 28S rRNA using gel electrophoresis.

 As a result, as shown in Figure 5, the integrity of the rRNA was 1.6 and 1.7 in the case of single administration and the rRNA integrity was 2.4 and 2.4 in the case of multiple administration (Fig. 5).

Example 1 Expression of FM0 Gene According to Mouse Tissue

 FM0 gene expression was confirmed in mouse liver, lung and kidney tissue.

Specifically, mice are euthanized with dichloromethan (CH ₂ C1 ₂ ), and liver, lung, and kidney tissues are obtained, and frozen before storage and stored. After frozen tissue is cut and homogenized with 1 ι of Trizol reagent, the samples are stored at room temperature for 5 minutes. Into this 0.2 niC chloroform, vortex the tube strongly for 15 seconds. Store for 2-3 minutes. Afterwards, the sample is centrifuged at 12000 rpm for 15 minutes at 4 ^° C, and the mixture is divided into a layer of phenol-chloroform at the bottom that appears red and a layer of water at the top without color. Transfer the water layer to a new tube, add isopropyl alcohol 0.5, homogenize, store at room temperature for 10 minutes, then centrifuge at 12000 rpm for 15 minutes at 4 ° C. The supernatant was removed and the precipitated RNA pellet was washed once with 75% ethanol (ethanol lOtOH 35 ni ^ + DEPC water 15 ηι 1 ^), and the samples were vortexed and mixed at 4 ^° C. Centrifuged at 7500 rpm for 5 minutes RNA pellets were dried and then 50 ill RNase-free water was added and stored for 10 minutes at 56 ^° C. The concentration of RNA thus obtained was determined using a NanoDrop 2000 UV spectrophotometer. The RNA obtained was determined by MoloML Murine Leukemia Virus reverse Transcriptase (Promega, CDNA synthesis was performed. The A / primer mixture was added to 5 RNA, oligo (dT) (0.5! Ig / id) 1 μl, DEPC treated water up to 10 ^ in a sterile PCR lye, and reacted at 70 ° C for 10 minutes. Leave on ice for at least 5 minutes. The reaction mixture was mixed with 5 X reaction buffer 4 i, 10 rnM dNTP mixture 2 βί, distilled water 2. 4 μΐ, RNase inhibitor (i nhi bi tor) 0.1 ^ and gently mixed with each RNA / primer mixture. , Simply centrifuge and collect. After placing it at 42 ^° C for 3 minutes, add 1 βί Μ-MLV reverse transcriptase, mix and place at 42 ^° C for 60 minutes. The reaction is left at 70 ° C for 5 minutes, cooled on ice, and then simply centrifuged to obtain reaction water. The resulting reaction product is immediately PCR or stored ^at -20 ^° C until the experiment.

RT-PCR is mixed with the running RNA 1; and the reverse primer in the PCR lyub using a primer designed as shown in Table 5 below, and reacted for 5 minutes at 70 ^° C and then placed on ice. Put a forward primer on it. Fill with DEPC water so the reaction volume is 20 ^. This was performed under PCR conditions as shown in Table 6 below. PCR result was confirmed by electrophoresis using a 1.0% agarose gel, the image was confirmed by LAS-3000.

 Table 5

 primer

Gene Name Sequence Direction Tissue Sequence Number Used

 FM01_F CAT TCC AAC TAC AAG GAC TCG Forward SEQ ID NO: 1

FM01 height

 FM01_R TGT CTC TGG ACA GTG GGA AGT Reverse SEQ ID NO: 2

FM02_F CCG GGT CH TAA GGG ITT CAG G Forward SEQ ID NO: 3

FM02 lung

 FM02_R AGG CTC CAT CTT CCC AAC CGT A Reverse SEQ ID NO: 4

FM03_F CAG CAT TTA CCA ATC GGT CTT C Forward SEQ ID NO: 5

FM03 liver

 FM03_R ΉG CTG TGA TGC ATG AAG TTG Reverse SEQ ID NO: 6

FM04_F TCC TGA GCC CAC ATT TAC CTC ο ο ο SEQ ID NO: 7

FM04 height

 FM04 ᅳ R CCA GTG TTT CCA AGA CCA ACC Reverse SEQ ID NO: 8

FM05_F GCT TGC CTA CAC GGT TCA AG Forward SEQ ID NO: 9

FM05 liver

 FM05_R ATC ACA CGG ATG CTC ACC TG Reverse SEQ ID NO: 10

GAPDH_F AGC CTC GTC CCG TAG ACA AA Forward SEQ ID NO: 11

GAPDH

GAPDH_R CAC GAC ATA CTC AGC ACC GGC Reverse SEQ ID NO: 12 [Table 6]

 As a result, as shown in Figure 6, even in the same FM0 gene group (gene fami ly), it was confirmed that the difference in the expression amount according to the tissue (Fig. 6). Example 8 Confirmation of Expression Change of FM0 Gene According to Extract Treatment by Mouse Organs

 Changes in FM0 gene expression according to extract treatment in mouse liver, lung and kidney organs were confirmed.

 Specifically, the animal model orally administered with the extract by the method described in Example <2-2>, was confirmed by RT-PCR in the same experimental method as the <Example 7>.

 As a result, as shown in Figure 7, the results of the results similar to the <Example 5> in the liver FM03 and kidney in the FM04 in the situation mushroom hot water extract (PBE), mushroom mushroom water fraction (PBW) and situation mushroom beta glucan ( In the group treated with PBG), it was confirmed that the expression level increased more than the group treated without PBG), and the expression of FM03 was more obvious in the group treated with the situation mushroom beta glucan than the mushroom mushroom hot water extract or the mushroom mushroom layer fraction. It was confirmed that the appearance (Fig. 7).

Example 9 Confirmation of Expression Analysis of FM03 Gene in Mouse Tissues

 As in <Example 8>, it was confirmed that beta glucan (β-D-glucan) of the situation mushroom promoted the expression of FM03 in the liver of the mouse, but the situation mushroom was very expensive and extracted from yeast or plants having a lower price than this. In order to determine whether beta glucan also promotes the expression of FM03, after the oral administration of various beta glucan for 7 days, FM03 expressed in the liver of rats was analyzed by real time PCR.

Specifically, SD rats were acclimated to the kennel for one week and then grouped into four groups (n = 4). Dilute saline (Control). Beta-glucans from S. mushrooms (PBG), yeast (Zymosan, Sigma-Aldr ich Co .. USA) and barley (Barley, Sigma-Aldr ich Co., USA) once daily at a concentration of 25 mg / kg, total Liver was harvested after oral administration for 7 days. In order to perform RNA isolation from the extracted organ, 1 m £ TRIzol reagent was applied to each tissue, and total RNA was isolated using a homogenizer. 250 chloroform was added to the isolated RNA, mixed well, and centrifuged to separate the supernatant. RNA was precipitated using 550 ≠ isopropanol, washed with 75% ethanol and air dried. After RNA was dissolved in RNase free water, RA concentration was measured and then stored at -80 ^° C.

To synthesize cDNA by reverse transcription on the extracted RNA, oligo d (T) 15-mer (EBT-1523, Elpis Biotech.Korea), reaction buffer (50 niM Tris-HCl, 75 mM KCl, 3 mM MgC12, 10 mM DTT, cDNA was synthesized by treating RNA isolated with 10 mM dNTP and 200 unit M-MLV-RT (Moloney murine leukemia virus reverse transcriptase, Pr omega, USA). Real time PCR was performed using the synthesized cDNA. 2X Amp i gene qPCR Green Mix Lo-Rox (Enzo, # ENZ-NUC103) 10 f, forward primer 1 μί on plate for real time PCR (multiplate PCR plates 96-well clear. # LL9601, Bio-rad, United Kingdom) , reverse primer 1 i, template DNA 2! After distilled H20 6 / was added, optical adhesive covers (Applied Biosystems, USA) were covered. Centrifuge at 1500 rpm for 5 minutes and spin down to perform real time PCR using real time PCR instrument (CFX-Connect, Bio-rad). Polymerase activation 2 min, 95 ° C, 1 cycle, denaturat ion 5 sec, 95 ^° C , anneal ing / extension 30 sec, 65 ^° C, 40 cycles were performed.

 As a result, as shown in FIG. 12, rats were orally treated with physiological saline (control), PBG (situation mushroom beta glucan), Zymosan (yeast beta glucan), and Barley (barley beta glucan) at a concentration of 25 mg / kg, respectively, for 7 days. After administration, liver was isolated and FM03 expression was analyzed by real time PCR. As a result, it was 2.4 times (2.43 ± 0.34) in beta glucan, 2.9 times (2.94 ± 0.19) in yeast beta glucan, and 2.2 times in barley beta glucan. 2.15 土 0.31)) was confirmed to increase (Fig. 12).

In conclusion, the increase of FM03 by beta glucan was not limited to beta glucan of situational mushrooms but also by yeast and plant-derived barley beta glucan. It was confirmed. Therefore, the use of inexpensive yeast or barley-glucans rather than using expensive situation mushrooms increases the expression of FM03. Therefore, the release of various xenobiotics containing various N-, S- and P- absorbed in the body such as residual pesticides and nicotine can be effectively achieved by the increased FM03.

Example 10 Confirmation of Pesticide Degradation Using High-Performance Liquid Chromatography (HPLC)

 <10-1> Preparation for HPLC

 In the same manner as in Example <2-3>, with a pesticide orally administered animal model, samples were prepared to confirm pesticide decomposition of the situation mushroom extract using the HPIX method.

Specifically. Blood samples were taken using cardiac puncture. Lay down the mouse and insert 1 syringe with a 25 to 30 gauge needle attached slightly to the middle to the left behind the xiphoid cartilage. In order for the needle to enter the heart, it must be inserted 10 to 30 ^° from the horizontal axis of the sternum. Also. Immediately approach the heart at the time of maximum heartbeat and pull the syringe to collect blood when the needle is about 1 cm in length. Samples were taken every 0.5, 1, 1.5, 2, 6 and 12 hours after administration of carbohydrate extract or betaglucan for 7 days, followed by carbendazim. The sample thus obtained is shaken for 30 minutes with twice the volume of methanol (MeOH). Thereafter, centrifugation was performed at 1700 g for 15 minutes, and the organic solvent charge was removed. Used for HPLC analysis. <10-2> Confirmation of Pesticide Degradation Using HPLC

 Pesticide degradation was confirmed by HPLC analysis with the samples obtained using the method of Example <9-1>.

Specifically, HPLC used Dionex (Germany). The column used a reverse phase colunm (C18, 250 × 4.6 μμιη). The wavelength was 245 nm, and the sample The injection amount was 20 yL. Methanol: water (50:50) was used as a mobile phase, and the flow rate was set to 1 / min.

 As a result, as shown in Figures 8a to 11, the situation mushrooms administered by the amount of carbendazim remaining in the mouse body when the situation mushroom hot water extract or beta glucan was administered than when the situation mushroom hot water extract or beta glucan was not administered Hot water extract or beta glucan concentration was confirmed to decrease in proportion to (Fig. 8a to 11). Based on the results so far, by orally administering a situation mushroom extract or beta glucan, it was confirmed that significantly increased the expression of FM03 among the FM0 gene group in the liver and promoted the breakdown of carbendazim. By increasing the expression of FM03 using the situation mushroom extract or beta glucan of the present invention, by confirming that the degradation of N-, S-, P-containing foreign substances such as nicotine or pesticides in the body is promoted. It can be used as a composition for promoting degradation of foreign substances.

Preparation Example 1 Preparation of Health Functional Food

 <1-1> Health functional food containing mushroom extract

 Situation mushroom extract: 0.1-10% by weight ，

 Lipase: 0.001 to 0.01% by weight,

 Tertiary phosphate: 1 20% increase.

 Vitamin E: 0.01-0.1% by weight,

 Enzyme powder: 1 to 10% by weight.

 Lactobacillus: 0.1-10% by weight,

 Bacillus culture medium: 0.01 to 10% by weight, and

 Glucose: 20 to 90% by weight. <1-2> Health functional food containing yeast extract

 Yeast Extract: 0.1-10% by weight

 Lipase: 0.001 to 0.01% by weight,

 Tertiary calcium phosphate: 1 20% by weight,

Vitamin E: 0.01-0.1% by weight, Enzyme powder: 1 to 10% by weight,

 Lactobacillus: 0.1-10% by weight,

 Bacillus culture: 0.01-10% by weight, and

 Glucose: 20-90% by weight.

<1-3> Health functional food containing barley extract

 Barley extract: 0.1-10% by weight,

 Lipase: 0.001 0.01% by weight,

 Tricalcium phosphate: 1 20% by weight.

 Vitamin E: 0.01-0.1% by weight,

 Enzyme powder: 1 to 10% by weight,

 Lactic acid bacteria: 0.1 to 10% by weight,

 Bacillus culture medium: 0.01 to 10% by weight, and

 Glucose: 20-90% by weight.

Preparation Example 2 Preparation of Natural Drug

 <2-1> Preparation of powder

 2 g of mushroom extract or beta glucan of Example 1

 1 g lactose

 After mixing the above components, the airtight cloth was filled to prepare a powder.

<2-2> Preparation of the tablet

 100 nig of situation mushroom extract or beta glucan of Example 1

 Corn starch 100 nig

 100 nig lactose

 2 nig magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets. Preparation of <2 "3> Capsules

 100 nig of situation mushroom extract or beta glucan of Example 1

 Corn starch 100 mg

 100 nig lactose

 2 nig magnesium stearate

 After mixing the above components, the capsule was prepared by filling in gelatin capsules according to a conventional method for producing a capsule.

<2-4> Preparation of the injection solution

 Situation mushroom extract or beta glucan of Example 1 10

 Dilute hydrochloric acid BP until pH 3.5

 Sodium Chloride BP Max Ιι for Injection

Preparation Example 3 Preparation of Feed Additives

 <3-1> Preparation of a feed additive containing a mushroom extract

 The present inventors prepared a feed additive with a composition as follows using the situation mushroom extract as an active ingredient. Situation mushroom extract: 0.1-10% by weight.

 Lipase: 0.001-0.01% by weight,

 Tertiary calcium phosphate: 1-20% by weight,

 Vitamin E: 0.01-0.1% by weight ，

 Enzyme powder: 1 to 10% by weight,

 Lactobacillus: 0.1 to 10% by weight,

 Bacillus (Bac i l his) culture: 0.01 10% by weight, and

 Glucose: 20 to 90% by weight.

<3-2> Preparation of Feed Additives Containing Beta Glucan

The present inventors feed on the composition as follows by using beta glucan as an active ingredient An additive was prepared. Beta glucan: 0.1 to 10% by weight,

 Lipase: 0.001-0.01% by weight,

 Tertiary calcium phosphate: 1-20% by weight,

 Vitamin E: 0.01 to 0.1% by weight.

 Enzyme powder: 1 ~ 10%

 Lactobacillus: 0.1 10% by weight,

 Bacillus culture: 0.01 to 10% by weight. And

 Glucose: 20 to 90% by weight.

Production Example 4 Preparation of Feed

 <4-1> Preparation of feed containing situation mushroom extract

 The present inventors mixed the following components and produced them according to the conventional feed preparation method.

 50 g of the situation mushroom extract of Example 1

 Mushroom medium 200 g

 30 g of wheat bran

 Beet pulp 50 g

 220 g rice brew

 200 g of corn flakes

 40 g of whole soybeans

 100 g of starch

 200 g of corn silage

 180 g of corncob

 400 g of bean curd

 Rice 323 g

 Zeolite 14 g

40 g of tapioca <4-2> Preparation of Feed Containing Beta Glucan

 The present inventors mixed the following components and produced them according to the conventional feed preparation method.

 50 g of beta glucan of Example 1

 Mushroom medium 200 g

 30 g of wheat bran

 Beet pulp 50 g

 220 g rice brew

 200 g of corn flakes

 40 g of whole soybeans

 100 g of starch

 200 g of corn silage

 180 g of corncob

 400 g of bean curd

 Rice 323 g

 Zeolite 14 g

 40 g of tapioca

Claims

[Range of request]  [Claim 1]  Situation mushroom species) composition for promoting degradation of N-, S-, P-containing xenobiotics containing the extract as an active ingredient. [Claim 2] The composition of claim 1, wherein the extract is extracted with water, lower alcohols of Ci to C ₂ or a mixture thereof as a solvent. [Claim 3] The method according to claim 1, wherein the situation mushroom is N-, S-, P-containing exogenous, characterized in that the mushroom mushroom Baumi baumii or the mushroom mushroom Linteus (/ ¾e / / / / 2i / s Ji ^' nteus) Material decomposition promoting composition. [Claim 4]  The composition of claim 1, wherein the extract increases FM03 (Flavin-containing monooxygenase3) gene expression. [Claim 5]  The method of claim 1, wherein the N-. S-. The P-containing exogenous foreign substance is at least one selected from the group consisting of nicotine, pesticides and pharmaceuticals. S-. A composition for promoting P-containing exogenous degradation. [Claim 6] 6. The N- according to claim 5, wherein the pesticide is at least one selected from the group consisting of pesticides, fungicides and herbicides. S-, P- containing composition for promoting degradation of exogenous foreign substances. [Claim 7]  N_, S-, P-containing xenobiotics degradation accelerators containing extracts of / ¾e /// y? "S species as active ingredients. [Claim 8] Phellinus (/ ¾e //// 7 "s species ) to extract, as an active ^ingredient: containing N-, S- P- containing biological or foreign matter (xenobiotics) decomposition functional food for promoting the. [Claim 9]  Feed additive for promoting degradation of N-, S- and P-containing xenobiotics containing extracts of situational mushrooms (/ ¾e /// ?? s species) as active ingredients. [Claim 10]  A method for promoting degradation of N-, S-, P-containing exogenous substances, comprising administering ¾e //// 7i / s species extracts to a subject other than humans. [Claim 11]  Extract of a situation mushroom (/ ¾e //// s species) for use in promoting N-, S-, and P-containing exogenous degradation, or a composition containing the same as an active ingredient. [Claim 12]  N-, S- containing beta glucan (β-glucan) as an active ingredient. A composition for promoting P-containing exogenous degradation. [Claim 13] The method of claim 12, wherein the beta glucan is from any one selected from the group consisting of situation mushrooms, Ganoderma lucidum mushroom / 20 ^ 77 «lucidum, basidiomycetes such as Cordyceps, plants such as barley and fungi including yeast Separated A composition for promoting degradation of N-, S-, P-containing exogenous foreign substances, characterized in that. [Claim 14] The method of claim 12, wherein the beta-glucan is FM03 (Flavin-containing monooxygenase3) N-, S-, P- ¾ euyu biological or foreign matter decomposition promoting composition, characterized in that for increasing the gene expression. [Claim 15]  13. The N-. S-, P- containing exogenous foreign substance N-, characterized in that at least one selected from the group consisting of nicotine, pesticides and pharmaceuticals. S-, P- containing composition for promoting degradation of exogenous foreign substances. [Claim 16]  The composition of claim 15, wherein the pesticide is at least one selected from the group consisting of insecticides, fungicides, and herbicides. [Claim 17]  N- containing β-glucan as an active ingredient. S-. P-Containing Biomolecular Degradation Accelerator. [Claim 18]  N- containing β-glucan as an active ingredient. Health functional food for promoting degradation of S-, P- containing foreign foreign substances. [Claim 19] A feed additive for promoting degradation of N-, S- and P-containing exogenous foreign substances containing beta-glucan (β-glucan) as an active ingredient. [Claim 20]  N-, S- containing beta glucan (β-glucan) as an active ingredient. Method for Promoting P-Containing Exogenous Substances. [Claim 21] Beta-glucan (β-glucan) or composition containing the same as an active ingredient for use in promoting N-, S-, P-containing exogenous degradation. ^'