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WO2016159451A1 - Composition permettant de favoriser la dégradation de matière ex vivo, contenant n-, s- et p- et un extrait de phellinus linteus ou du bêta-glucane - Google Patents

Composition permettant de favoriser la dégradation de matière ex vivo, contenant n-, s- et p- et un extrait de phellinus linteus ou du bêta-glucane Download PDF

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Publication number
WO2016159451A1
WO2016159451A1 PCT/KR2015/008056 KR2015008056W WO2016159451A1 WO 2016159451 A1 WO2016159451 A1 WO 2016159451A1 KR 2015008056 W KR2015008056 W KR 2015008056W WO 2016159451 A1 WO2016159451 A1 WO 2016159451A1
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Prior art keywords
promoting
glucan
degradation
composition
extract
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English (en)
Korean (ko)
Inventor
김하원
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Industry Cooperation Foundation of University of Seoul
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Industry Cooperation Foundation of University of Seoul
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62D—CHEMICAL MEANS FOR EXTINGUISHING FIRES OR FOR COMBATING OR PROTECTING AGAINST HARMFUL CHEMICAL AGENTS; CHEMICAL MATERIALS FOR USE IN BREATHING APPARATUS
    • A62D3/00—Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances

Definitions

  • N- Containing situation mushroom extract or beta glucan as an active ingredient.
  • S- Composition for promoting degradation of P-containing exogenous substances
  • the present invention is N-. Containing a species mushroom extract) or beta glucan ( ⁇ -glucan) as an active ingredient. It relates to a composition for promoting the degradation of S-, P- containing xenobiotics.
  • S species is woody mud, which is known as the Phellinus li eus, but in Korea, the most common cultivar is the Shampoo Baumi (/ 3 ⁇ 4e ////? 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 ( ⁇ -secretase) inhibitory activity for the treatment of Alzheimer's disease have been reported, many studies have been concentrated on the mycelial culture of mushrooms.
  • 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).
  • betaglucan is a eukaryotic nutrient component, readily degraded to mammalian enzymes, and lacks immunostimulatory activity
  • 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 ..
  • 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 ⁇ containing monooxygenase is a group of enzymes that promote the oxidation of substrates primarily as nucleophiles through the cofactor, flavin.
  • 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.
  • 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.
  • FAD flavin adenosine dinucleotide
  • 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.
  • 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.
  • 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.
  • pesticides are harmful to crops, germs.
  • Pesticides 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.
  • 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.
  • 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 ⁇ -benz i ⁇ idazol-2-yl carbamate, CAS The number is 10605-21-7.
  • Nonsteroidal anti-inflammatory drugs 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.
  • Non-steroidal anti-inflammatory drugs similar to benzidamine include methyl p-tolyl sulfide (MTS) of formula (5), and sulindac sulfide of formula (6).
  • MTS methyl p-tolyl sulfide
  • An object of the present invention is to promote the degradation of xenobiotics containing N-, S-, P- containing 3 ⁇ 4e //// s species extract or beta-glucan as an active ingredient. It is to provide a composition for.
  • N-, S-, P-containing xenobiotics degradation accelerator which contains an extract of a situation mushroom (/ 3 ⁇ 4e ///// "s species) or beta glucan as an active ingredient.
  • 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 (/ 3 ⁇ 4e //// 7 "s species) or beta glucan as an active ingredient. To provide.
  • 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.
  • the present invention provides a N-, S-, P-containing xenobiotics degradation accelerator containing a situation mushroom (/ 3 ⁇ 4e //// 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 3 ⁇ 4e /// 2/2 species species as an active ingredient.
  • the present invention provides a feed additive for promoting degradation of N-, S-, P-containing xenobiotics, which contains an extract of a situation mushroom (/ 3 ⁇ 4e /////? 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 (/ 3 ⁇ 4e // s species) to an individual except a human.
  • the present invention provides a mushroom extract (/ 3 ⁇ 4e // ;; 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.
  • the present invention N-, S-, containing beta glucan ( ⁇ -glucan) as an active ingredient
  • composition for promoting P-containing exogenous degradation is provided.
  • the present invention provides an N-, S-, P-containing exogenous biodegradation accelerator containing beta-glucan as an active ingredient.
  • the present invention provides a feed additive for promoting the degradation of N-, S-, P-containing exogenous substances containing beta glucan ( ⁇ -glucan) as an active ingredient.
  • the present invention N-. Containing beta glucan ( ⁇ - glucan) as an active ingredient. Provided is a method for promoting degradation of S- , P- containing exogenous foreign substances.
  • the present invention is N-, S-. It provides beta glucan ( ⁇ -glucan) or a composition containing the same as an active ingredient for use in promoting P-containing exogenous degradation.
  • La is a histogram showing the results of analysis of hepatic gene expression changes in the situation mushroom species) 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.
  • RNA quality (qual i ty) in the situation mushroom hot water extract (PBE) administration group:
  • FM0 F 1 av i n-cont a n i ng monooxygenase
  • Tissues Type of Tissue
  • Liver Liver Tissue
  • Lung lung tissue
  • Kidney 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; Kidney tissue;
  • PBW situation mushroom aqueous fraction treatment group
  • PBG situation mushroom beta glucan treated group
  • FIG. 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
  • 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
  • D is The result is 2 hours after oral carbendazim
  • (E) is 6 hours after oral carbendazim
  • (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
  • 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
  • 11 is a graph showing the results of analysis by HPLC.
  • FIG. 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
  • Barley 25 mg / kg
  • PBG Phellinus baumii ⁇ -D-glucan
  • the present invention is N-. Containing a situation mushroom species extract or beta glucan ( ⁇ - glucan) as an active ingredient.
  • a composition for promoting degradation of S-, P-containing xenobiotics is provided.
  • the situation mushroom extract is preferably prepared by a manufacturing method including the following steps, but is not limited thereto.
  • 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.
  • the extraction time is preferably 1 to 36 hours, preferably 9 to 24 hours. It is not limited to this.
  • the decompression concentration in step 3) may be to use a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto.
  • 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 (/ 3 ⁇ 4e /// s bau ii) or mushroom mushroom Linteus (A3 ⁇ 4e /// 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.
  • 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).
  • SEQ ID NO: 13 GenBank Accession No .: NM—008030.
  • 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).
  • 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).
  • 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).
  • HPLC high-performance liquid chromatography
  • 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.
  • 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-, ⁇ S-, P-.
  • 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.
  • 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.
  • an excipient or diluent it may be formulated as a pharmaceutical composition by conventional methods.
  • 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.
  • 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.
  • Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups.
  • various excipients for example, wetting agents, sweeteners, fragrances, and preservatives, may be included. have.
  • Formulations for parenteral administration include external skin preparations.
  • 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
  • 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.
  • 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.
  • the pharmaceutical composition of the present invention 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.
  • 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.
  • 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 ⁇ chitosan.
  • 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 ⁇ chitosan.
  • phosphates such as potassium phosphate, sodium phosphate, polymerized phosphate, polyphenols, catechin tocopherol, vitamin C , Green tea extract
  • diluents may be additionally added to formulate injectable formulations , capsules , granules or tablets such as aqueous solutions and suspension emulsions.
  • 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, 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.
  • 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.
  • animal diets 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. ⁇ Q
  • the present invention comprises the step of administering a situation mushroom extract or beta glucan to a subject other than human.
  • a method for promoting S- and P-containing exogenous degradation is provided.
  • Subjects except humans except humans Sheep, pigs, goats, camels, antelopes. Cows, chickens. Duck, dog. Means animals such as cats.
  • N- ⁇ 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.
  • 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-.
  • the present invention will be described in detail by way of examples.
  • the extraction yield is the temperature, the amount of purified water, PH.
  • extraction time is 85 ° C, 90 ° C. 95 ° C. 100 ° C., 105 ° C. and 110 ° C.
  • extraction times are 9 hours, 18 hours and 24 hours.
  • 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.
  • the extract was mass-produced using the above method.
  • the pulverized mushroom mushroom pieces and 20 ⁇ purified water were added to a 200 ⁇ 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.
  • 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 ⁇ , and then lyophilized. / 3 ⁇ 4e /////? "S bauwii ext ract, PBE).
  • 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.
  • penicillin 10,000 units / mO-streptoinycin
  • FBS Fetal Bovine Se
  • mice 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 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 ⁇ 2-2> 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.
  • mice 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.
  • cutof f 2.0 was set based on Table 2, and specific gene clustering was performed using hierarchical clustering.
  • 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.
  • Example 3> 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).
  • 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.
  • 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).
  • FM0 gene expression was confirmed in mouse liver, lung and kidney tissue.
  • 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 ⁇ 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.
  • dichloromethan CH 2 C1 2
  • Trizol reagent Trizol reagent
  • RNA pellet was washed once with 75% ethanol (ethanol lOtOH 35 ni ⁇ + DEPC water 15 ⁇ 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.
  • 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 ⁇ l, 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 ⁇ , distilled water 2. 4 ⁇ , RNase inhibitor (i nhi bi tor) 0.1 ⁇ and gently mixed with each RNA / primer mixture. , Simply centrifuge and collect.
  • 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.
  • Example 7> 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>.
  • 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.
  • 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.
  • 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.
  • 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 ⁇ 0.31)) was confirmed to increase (Fig. 12).
  • 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 ⁇ 2-3> 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.
  • Pesticide degradation was confirmed by HPLC analysis with the samples obtained using the method of Example ⁇ 9-1>.
  • HPLC used Dionex (Germany).
  • the column used a reverse phase colunm (C18, 250 ⁇ 4.6 ⁇ ).
  • 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.
  • Lipase 0.001 to 0.01% 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 medium 0.01 to 10% by weight
  • 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
  • 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
  • Glucose 20-90% by weight.
  • Barley extract 0.1-10% 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
  • Glucose 20-90% by weight.
  • the airtight cloth was filled to prepare a powder.
  • the capsule was prepared by filling in gelatin capsules according to a conventional method for producing a capsule.
  • 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.
  • 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
  • Glucose 20 to 90% by weight.
  • 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
  • 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.
  • Glucose 20 to 90% by weight.
  • the present inventors mixed the following components and produced them according to the conventional feed preparation method.
  • the present inventors mixed the following components and produced them according to the conventional feed preparation method.

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Abstract

La présente invention a confirmé que le bêta-glucane (β-glucane) extrait et raffiné à partir de Phellinus Linteus (espèce Phellinus), de levure, d'orge ou analogue augmente l'expression du gène FM03 en particulier parmi les groupes de gènes FM0 dans le foie et favorise la dégradation du carbendazime qui est un pesticide contenant de l'azote dans une matière vivante. Par conséquent, la présente invention peut être utilisée en tant que composition, pour favoriser la dégradation de matière ex vivo, contenant N-, S-et P- et un extrait de Phellinus Linteus ou du bêta-glucane.
PCT/KR2015/008056 2015-04-02 2015-07-31 Composition permettant de favoriser la dégradation de matière ex vivo, contenant n-, s- et p- et un extrait de phellinus linteus ou du bêta-glucane Ceased WO2016159451A1 (fr)

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Citations (3)

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KR100707917B1 (ko) * 2005-12-06 2007-04-13 주식회사 글루칸 베타 글루칸을 유효성분으로 포함하는 간질환 치료용 약학조성물
KR20110095486A (ko) * 2010-02-19 2011-08-25 전북대학교산학협력단 바우미 상황버섯 유래의 폴리페놀 추출물을 유효성분으로 함유하는 고지혈, 지방간 또는 비만 예방 및 치료용 조성물

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