KR20140026737A - A composition comprising the powder of fermented curcuma longa l. for protecting alcoholic liver damage - Google Patents

Abstract

The present invention relates to a composition containing fermented Curcuma longa powder for treating alcoholic liver damage. The fermented Curcuma longa powder of the present invention is obtained by fermenting materials for the fermented Curcuma longa powder using Aspergillus oryzae, and sterilizing and drying the materials, and shows a strong liver damage control function in an alcoholic liver damage model. The composition can be practically used for treatment and prevention food for alcoholic liver damage, medical products, and outer medical products using the fermented Curcuma longa powder.

Description

A composition comprising the powder of fermented Curcuma Longa L. for protecting alcoholic liver damage}

The present invention relates to an alcoholic liver damage protection composition containing a fermented turmeric powder for fermented turmeric powder.

[Document 1] Kim Chang-min, Shin Min-kyo et al., Jungdam Book Publishing, Chinese Medicinal Dictionary, Vol. 7, pp3282-3287, 1997

Murakmi T, Kim T, Nakamura H. 1998. Hepatitis, cirrhosis, and hepatoma. J Magn Reson Imaging 8: 346-358.

Kim YJ, You YH and Jun WJ: Hepatoprotective activity of fermented Curcuma longa L. on galactosamine-intoxicated rats. J Korean Soc Food Sci Nutr 41: 790-795, 2012.

Das SK and Vasudevan DM: Alcohol-induced oxidative stress. Life Sci 81: 177-187, 2007.

Polavarapu R, Spitz DR and Sim JE: Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology 27: 1317-1323, 1998.

Chillungham, Cunnungham CC, Adachi M, Ishii H, Bailey SM and Fromenty B: Effects of alcohol and oxidative stress on liver pathology: role of the mitochondrion. Alcohol Clin Exp Res 26: 907-915, 2002.

The liver is a very important organ that is responsible for various metabolism, detoxification, decomposition, synthesis and secretion in our body. First, the liver has the function of managing the energy metabolism, and metabolizes all the nutrients absorbed from food into a substance capable of producing energy, and supplies or stores the whole body. Second, the liver has a function of synthesizing, storing and distributing fat of about 2,000 kinds of enzymes, albumin, serum proteins of bile coagulation factors, bile acid, phospholipid and cholesterol. Third, the liver has a function to excrete various metabolites through the bile duct into the duodenum, and it plays an important role in maintaining our life because of its immune function. Finally, the liver has detoxification and decomposition functions to detoxify drugs, toxic substances and alcohol. However, the hepatocyte detoxification function of this liver is liable to damage the drug, toxic and alcoholic liver disease can cause.

Alcoholic liver disease can be divided into alcoholic fatty liver disease, alcoholic hepatitis, and alcoholic cirrhosis according to the clinical symptoms. It usually occurs when 60 to 80 g of alcohol is consumed for 10 years. Alcoholic fatty liver is caused by accumulation of cholesterol and triglyceride in hepatocyte due to excessive alcohol consumption. It can be recovered soon after this week, but if it continues drinking, it develops into hepatitis. Alcoholic hepatitis has necrosis and inflammation of hepatocytes, and it has various symptoms such as fatigue, anorexia, weight loss, jaundice, fever, right upper abdominal pain, and about 40% of the patients develop alcoholic cirrhosis. Alcoholic cirrhosis is a condition that is impossible to recover from normal liver, and has various symptoms such as general fatigue, decreased appetite, ascites, esophageal varices, bleeding, hepatic encephalopathy, lethargy, and poor prognosis than cirrhosis caused by hepatitis virus. In Esau, 50% of deaths from end-stage liver disease are known to be caused by alcohol.

Alcoholic liver disease can be divided into alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis according to clinical symptoms, and it usually occurs when people drink 60-80g of alcohol a day for 10 years. Alcoholic fatty liver is caused by accumulation of cholesterol and triglyceride in hepatocyte due to excessive alcohol consumption. It can be recovered soon after this week, but if it continues drinking, it develops into hepatitis. Alcoholic hepatitis has necrosis and inflammation of hepatocytes, and it has various symptoms such as fatigue, anorexia, weight loss, jaundice, fever, right upper abdominal pain, and about 40% of the patients develop alcoholic cirrhosis. Alcoholic cirrhosis is a condition that is impossible to recover from normal liver, with various symptoms such as systemic fatigue, loss of appetite, ascites, esophageal varices, bleeding, hepatic encephalopathy, lethargy, and poor prognosis than cirrhosis caused by hepatitis virus. In Esau, 50% of deaths from end-stage liver disease are known to be caused by alcohol.

In order to reduce the alcoholic liver disease mortality as described above, there is an urgent need to develop alcoholic liver injury prevention and treatment, but until now, no appropriate therapeutic agent, health functional food, and related composition for treating alcoholic liver injury have been developed. Therefore, in order to reduce the mortality rate of alcoholic liver disease, alcoholic fatty liver, which is the initial alcoholic liver disease, should be treated appropriately. However, to date, no appropriate therapeutic agent has been developed to treat the disease.

The tuber of Curcuma Longa L., the ginger family, is dried or steamed after removing the bark. In Japan, it is root stem. In China, Curcuma kwangsiensis SG Lee & CF Liang (廣西 莪 朮), Curcuma wenyujin YH Chen & C. Ling (溫 郁金) and Curcuma phaeocaulis Valeton (蓬 莪 朮) Roots of the roots (Curcuma longa Linn), also known as fall turmerics. It is similar in appearance to Curcuma longa Linn, but has smooth features on both sides of the leaves. It is grown and cultivated in South China, India, Okinawa, and Southeast Asia. When it is mixed with alcohol, it is a yellowish gold name and its shape is similar to Azul and it is called magic because it treats diseases of horses (document 1: Kim Chang-min, Shin Min-gyo et al., Jungdam Book Publishing, Chinese Medicine Dictionary, 7 Kwon, pp 3282-3287, 1997).

Turmeric has been recorded since BC, used as dyes and food colorings, and is a source of Indian curry. In Japan, turmeric is used as a coloring material for radish, and it is grown as a special crop in Okinawa, Japan, which is known as a longevity village in the world, and is used as a health food.

Accordingly, the present inventors exhibited the effect of inhibiting alcoholic liver damage in alcoholic liver damage model of fermented turmeric powder obtained by fermenting turmeric with sterile bacterium and sterilizing and drying the fermented turmeric powder of the present invention to treat alcoholic liver disease and The present invention has been found to be useful for prevention.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the treatment and prevention of alcoholic liver injury diseases containing fermented turmeric powder as an active ingredient.

Alcoholic liver injury diseases as defined herein include alcoholic fatty liver, alcoholic hepatitis, alcoholic cirrhosis, preferably alcoholic fatty liver.

Hereinafter, the present invention will be described in detail.

Fermentation turmeric of the present invention can be obtained as follows.

The fermented turmeric powder as defined herein is dried in the form of S. aureus (fungus of the genus Aspergillus), preferably S. aureus Aspergillus Oryzae was inoculated at 0.120%, preferably, 110%, more preferably 15% (v / v%) relative to the powder in turmeric samples which had been dried and sterilized, and the fermentation temperature was 150 ° C., preferably At 1040 ° C, more preferably 2090 ° C, 2090% relative humidity of water, preferably 4080%, more preferably 5070%, fermentation time 1 hour to 1 week, preferably 2 days to Fermentation turmeric powder obtained through a process comprising fermentation, sterilization, drying and powdering for 5 days, more preferably about 30 to 50 hours.

Accordingly, the present invention provides a pharmaceutical composition for the protection of alcoholic liver damage containing the powder as an active ingredient in the production method.

The composition for preventing and treating alcoholic liver disease of the present invention includes the powder in an amount of 0.1 to 99% by weight based on the total weight of the composition.

However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

The composition comprising the powder of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

Compositions comprising powders according to the invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, or external preparations, respectively, according to conventional methods, In addition, carriers, excipients and diluents that may be included in the composition comprising the powder of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium Phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . The external preparation for parenteral administration includes sterilized aqueous solution, non-aqueous solution, suspension, emulsion, freeze-dried preparation, and suppository. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the powders of the present invention vary depending 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, the powder of the present invention is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 g / kg to 5 g / kg per day. The administration may be carried out once a day or divided into several doses. Accordingly, the dosage is not limited in any way to the scope of the present invention.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

The present invention also provides a health functional food for the prevention and improvement of alcoholic liver injury diseases containing the fermented turmeric powder as an active ingredient.

Therefore, the present invention also provides a food and food additive containing the fermented turmeric powder having the protective effect of alcoholic liver damage as an active ingredient.

The composition containing the powder of the present invention can be used in various ways, such as drugs, foods and drinks for the prevention and improvement of alcoholic liver disease. Foods to which the powder of the present invention can be added include, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, in the form of powders, granules, tablets, capsules, or beverages. Can be used.

Since the powder of the present invention has little toxicity and side effects, it is a drug that can be used safely even when taken for a long time for the purpose of prevention.

The powder of the present invention may be added to food or beverage for the purpose of preventing and improving alcoholic liver disease. At this time, the amount of the powder in the food or beverage is generally the health food composition of the present invention can be added to 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.02 to 10 g based on 100 ml, preferably It can be added at a ratio of 0.3 to 1 g.

The health beverage composition of the present invention, in addition to containing the powder as an essential ingredient in the indicated ratio, is not particularly limited in the liquid component, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the above-mentioned natural carbohydrates are conventional monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and polysaccharides such as dextrin, cyclodextrin and the like. Sugars and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tautin, stevia powder (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

As described above, the fermented turmeric powder of the present invention not only has alcohol-induced liver damage protection effect, but also shows hepatic damage inhibition effect by inhibiting hepatocellular lipid peroxidation and maintaining liver antioxidant and antioxidant enzyme activity. Fermented turmeric powder of can be usefully used as a composition for the treatment and prevention of alcoholic liver damage

1 is a graph showing the results of experiments confirming the effect of inhibiting the ALT and AST activity by alcohol of fermented turmeric powder in C57BL / 6 mice.
2 is a graph showing the results of experiments confirming the inhibitory effect of lipid peroxide production of C57BL / 6 mouse liver tissues by treatment with fermented turmeric powder.
Figure 3 is a graph showing the results of experiments to determine the content of antioxidant in the reduced glutathione content of C57BL / 6 mouse liver tissue according to fermented turmeric powder treatment.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the present invention is not limited to the following Examples and Experimental Examples.

Example  One. Fermented turmeric  Preparation of powder

100 kg of turmeric dried powder, powdered and pulverized by cutting and drying turmeric obtained from the Jindo Turmeric Farming Association, Jisan-myeon, Jindo-gun, was used as raw materials.

Strains used for fermentation were Hwangkuk bacteria purchased from Chungmu fermentation (Kukgi Aspergillus oryzae was purchased from Chungmu fermentation.

Fermented turmeric as defined herein is dried dried Aspergillus oryzae is prepared to purchase at Chungmu fermentation, CF1001), and turmeric are dried after the surface was washed three times with water flowing through the tube as turmeric magnitude cultivation acid were cut (5 mm or less in thickness). The turmeric which passed through 100mesh sieve after drying for 24 hours (less than 5% of water content) with a heat dryer (instead of pores), followed by the process of 1st grinding (adjustment), 2nd grinding (milling), and 3rd grinding (dusting). The powder was airtightly packed and stored at room temperature to prepare.

The prepared turmeric powder was prepared by adding sulfuric acid bacteria to the solid fermenter possessed by the Kyungpook Bio Industry Research Institute located in Andong, Gyeongsangbuk-do (sterilization condition 121 ℃, 1.0 atm, 20min).

Experimental Example 1. Evaluation of the inhibition of alcoholic liver damage of fermented turmeric powder

Using the fermented turmeric powder of the present invention obtained in the above example, the alcoholic liver damage inhibition activity was measured using the method described in the literature as follows (You YH, Yoo SN, Yoon HG, Park JJ, Kim SH, Oh KT, Lee JM, Cho HY and Jun WJ: In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress.Food Chem Toxicol 48: 16321637, 2010).

Hepatoprotective activity of the samples was performed in male C57BL / J mice. C57BL / J mice were acclimated to the nursery environment for 1 week after purchase, and randomly assigned to 8 animals in 4 groups. Control group (N.cont), ethanol control group (P.cont), fermented turmeric powder low concentration (100 mg / kg / day) administration group (FC-L), fermented fermented turmeric powder high concentration (300 mg / kg / day) administration group (FC -H) and each sample was orally administered for 5 days. The control group and the ethanol control group were orally administered water with the fermented turmeric group. The ethanol 5 g / kg / day was administered to the P.cont, FC-L, FC-H group for 6 days, 7 days, 8 days, and dissected 6 hours after the last administration to extract blood and liver tissue.

ALT (aspartate aminotransferase) and AST (alanine aminotransferase) were assessed by using blood. As shown in Figure 1 fermented turmeric powder was shown to have a protective effect against liver cell damage caused by alcohol. In addition, as a result of comparing the lipid peroxide content of liver tissue in the liver due to alcoholic liver damage in each group, it was confirmed that the lipid peroxide increased by alcohol as a result of the administration of fermentation turmeric. In addition, as a result of comparing glutathione, a powerful antioxidant protein of liver tissue in each group, it was confirmed that the glutathione content reduced by alcohol was maintained in the fermented turmeric administration group as shown in FIG. 3. In addition, the protective effect on the antioxidant enzyme activity reduced by alcohol was confirmed as shown in Table 1.

The results showed that fermented turmeric powder had a protective effect against hepatocellular damage caused by alcohol.

Antioxidant Enzyme Activity of C57BL / 6 Mouse Liver Tissue Treated with Fermented Turmeric Powder SOD CAT GST GPX GR U / mgprotein U / mgprotein U / mgprotein U / mgprotein U / mgprotein N.con 19.31 ± 0.58 ^b 244.80 ± 15.84 ^a 5.82 ± 0.20 ^a 0.76 ± 0.04 ^a 1.53 ± 0.05 ^a P.con 16.67 ± 0.54 ^c 142.63 ± 14.21 ^c 4.83 ± 0.17 ^b 0.61 ± 0.01 ^b 1.33 ± 0.02 ^b FC-L 18.01 ± 0.81 ^bc 212.00 ± 15.16 ^b 5.14 ± 0.21 ^b 0.62 ± 0.03 ^b 1.37 ± 0.03 ^b FC-H 22.07 ± 0.89 ^a 271.05 ± 8.49 ^a 5.06 ± 0.25 ^b 0.64 + 0.02 ^b 1.46 ± 0.03 ^b

Hereinafter, formulation examples of the composition containing the compound of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.

Formulation example  One. Sanje  Produce

Fermented turmeric powder (FC) -------------------------------------- 200 mg

Lactose ------------------------------------------------- - 100 mg

Talc ------------------------------------------------- --- 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

Formulation example  2. Preparation of tablets

Fermented turmeric powder (FC) -------------------------------------- 200 mg

Corn Starch --------------------------------------------- 100 mg

Lactose ------------------------------------------------- - 100 mg

Magnesium Stearate -------------------------------------- 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation example  3. Preparation of capsules

Fermented turmeric powder (FC) -------------------------------------- 200 mg

Crystalline cellulose ---------------------------------------- 3 mg

Lactose ----------------------------------------------- 14.8 mg

Magnesium stearate 0.2 mg < RTI ID = 0.0 >

The above components are mixed in accordance with a conventional method for producing a capsule, and filled in a gelatin capsule to prepare a capsule.

Formulation example  4. Preparation of injections

Fermented turmeric powder (FC) -------------------------------------- 200 mg

Mannitol ------------------------------------------------- 180 mg

Sterile Distilled Water for Injection ------------------------------------ 2974 mg

Na ₂ HPO _{4 ,} 12H ₂ O ------------------------------------------ --- 26 mg

(2 ml) per ampoule in accordance with the usual injection method.

Formulation example  5. Liquid  Produce

Fermented turmeric powder (FC) -------------------------------------- 200 mg

Isseong Party ------------------------------------------------ - 10 g

Mannitol ------------------------------------------------- --- 5 g

Purified water ------------------------------------------------- - Suitable amount

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation example  6. Manufacture of health food

Fermented turmeric powder (FC) -------------------------------------- 1000 mg

Vitamin mixture ---------------------------------------------

Vitamin A Acetate -------------------------------------- 70 g

Vitamin E ------------------------------------------------ 1.0 mg

Vitamin B1 ---------------------------------------------- 0.13 mg

Vitamin B2 ---------------------------------------------- 0.15 mg

Vitamin B6 ----------------------------------------------- 0.5 Mg

Vitamin B12 ---------------------------------------------- 0.2 g

Vitamin C ------------------------------------------------ - 10 mg

Biotin ------------------------------------------------- - 10 [mu] g

Nicotinic acid amide 1.7 mg

Folic acid ------------------------------------------------- ---- 50 μg

Calcium pantothenate ------------------------------------------- 0.5 mg

Inorganic mixture ---------------------------------------------

Ferrous sulfate ---------------------------------------------- 1.75 mg

Zinc oxide ----------------------------------------------- 0.82 Mg

Magnesium carbonate - 25.3 mg

Potassium monophosphate ---------------------------------------------- 15 mg

Calcium Phosphate ---------------------------------------------- 55 mg

Potassium citrate ----------------------------------------------- 90 Mg

Calcium Carbonate ------------------------------------------------ 100 mg

Magnesium chloride ------------------------------------------- 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

Formulation example  7. Manufacture of health drinks

Fermented turmeric powder (FC) -------------------------------------- 1000 mg

Citric acid ------------------------------------------------- 1000 mg

Oligosaccharide ------------------------------------------------ 100 g

Plum concentrate ------------------------------------------------ 2 g

Taurine ------------------------------------------------- --- 1 g

Purified water was added.

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (6)

A pharmaceutical composition for the treatment and prevention of alcoholic liver injury diseases containing fermented turmeric powder as an active ingredient. The pharmaceutical composition of claim 1, wherein the alcoholic liver disease is alcoholic fatty liver, alcoholic hepatitis, or alcoholic cirrhosis. Health functional food for the prevention and improvement of alcoholic liver injury disease containing fermented turmeric powder as an active ingredient. The dietary supplement according to claim 3 in the form of a powder, granule, tablet, capsule or beverage. Food and food additives containing fermented turmeric powder having an alcoholic liver damage protection effect as an active ingredient. The food and food additive according to claim 5, which are various foods, beverages, gums, teas, vitamin complexes, or health supplements of candy.

Images