KR20020021980A - Improving agent of alcoholic metabolism and decreasing agent of troubles in liver - Google Patents

Improving agent of alcoholic metabolism and decreasing agent of troubles in liver Download PDF

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KR20020021980A
KR20020021980A KR1020010030431A KR20010030431A KR20020021980A KR 20020021980 A KR20020021980 A KR 20020021980A KR 1020010030431 A KR1020010030431 A KR 1020010030431A KR 20010030431 A KR20010030431 A KR 20010030431A KR 20020021980 A KR20020021980 A KR 20020021980A
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alcohol
carbon tetrachloride
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기무라아키히코
다카다아쯔시
오오모리마사키
오카다도시타카
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기무라 아키히코
가부시키가이샤 도요학코
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Abstract

PURPOSE: An alcohol metabolism improving agent and a liver disorder reducing agent are provided, therefore the liver disorder caused by alcohol and carbon tetrachloride can be alleviated. CONSTITUTION: The alcohol metabolism improving agent is produced by inoculating Bacillus subtilis into a medium containing rice sugars, soybeans and carbon source, and fermenting the medium, in which the rice sugars include rice embryo, defatted rice embryo,, rice sugar and defatted rice sugar; the soybeans include defatted soybean, bean powder, soybean powder, soybean paste and hydrolyzed products thereof; and the carbon source is any one selected from glucose, dextrin, lactose and amyloid; the rice sugars are added in the amount of 100 parts by weight; the soybeans are added in the amount of 10 to 20 parts by weight; and the carbon source is added in the amount of 20 to 80 parts by weight. The liver disorder reducing agent is produced by inoculating Bacillus subtilis into a medium containing rice sugars, soybeans and carbon source, and fermenting the medium, in which the liver disorder is caused by alcohol and halogen compounds such as carbon tetrachloride.

Description

알콜대사 향상제 및 간장애 저감제{IMPROVING AGENT OF ALCOHOLIC METABOLISM AND DECREASING AGENT OF TROUBLES IN LIVER}IMPROVING AGENT OF ALCOHOLIC METABOLISM AND DECREASING AGENT OF TROUBLES IN LIVER}

본 발명은 알콜대사 향상제 및 간장애 저감제에 관한 것으로서, 보다 상세하게는 미당ㆍ대두 발효추출물을 함유하며, 알콜대사를 향상시키는 알콜대사 향상제,및 간장애, 특히 알콜이나 사염화탄소 등의 할로겐화합물에 기인하는 간장애를 저감할 수 있는 간장애 저감제에 관한 것이다.The present invention relates to an alcohol metabolism improving agent and an agent for reducing liver disorders, and more particularly, to an alcohol metabolism improving agent which contains an unsweetened sugar and soybean fermented extract and improves alcohol metabolism, and a liver disorder, especially a halogen compound such as alcohol or carbon tetrachloride. It relates to a liver disorder reducing agent that can reduce the resulting liver disorders.

에탄올을 섭취하면, 간장에서 알콜 탈수소효소(ADH)의 작용에 의해서 이 에탄올이 산화되어, 아세트알데히드로 다시 변환된다. 아세트알데히드는 알데히드 탈수소효소(ALDH)의 작용에 의해서 초산으로 변환되어, 체외로 배설된다. 그러나, 알콜대사 생성물인 아세트알데히드가 충분하게 대사되지 않아서 체내에 축적되면, 피부홍조, 두통, 구역질 등의 숙취증상을 나타낸다. 이점에서, 종래부터 생체내에서 안전하고 우수한 알콜대사 향상작용을 나타내는 알콜대사 향상제의 출현이 요구되고 있다.When ethanol is ingested, the ethanol is oxidized by the action of alcohol dehydrogenase (ADH) in the liver and converted to acetaldehyde again. Acetaldehyde is converted to acetic acid by the action of aldehyde dehydrogenase (ALDH) and excreted in vitro. However, when acetaldehyde, an alcohol metabolic product, is not sufficiently metabolized and accumulated in the body, symptoms of hangover such as skin flushing, headache, and nausea are exhibited. In view of the above, there has been a demand for the emergence of an alcohol metabolism improving agent which shows a safe and excellent alcohol metabolism improving action in vivo.

또한, 간장은 해독, 물질대사 등에 중심적인 역할을 담당하고 있으며, 각종 기능을 보유하는 주요한 장기로 작용하고 있지만, 간염 바이러스의 감염에 의한 것 이외에도, 클로로포름, 사염화탄소, 비스페놀, 프탈산에스테르, 염화화합물, 알킬페놀, 알콜류 등의 화학물질에 의해, 간장애가 발생된다는 사실이 알려져 있다. 특히 약물의 부작용으로 발생하는 약물성 간장애는 약물의 유효성을 감쇄하기 때문에 문제가 된다. 또한, 최근의 알콜 섭취량 증가에 따라, 알콜 섭취에 기인하는 알콜성 간장애도 문제가 되고 있다. 이점에서, 종래보다 효과적인 간장애 저감제의 개발이 요구되고 있다.In addition, the liver plays a central role in detoxification, metabolism, etc., and acts as a major organ with various functions, but in addition to infection by hepatitis virus, chloroform, carbon tetrachloride, bisphenol, phthalate ester, chloride compound, It is known that liver disorders are caused by chemicals such as alkylphenols and alcohols. In particular, pharmacologic liver disorders caused by side effects of drugs are problematic because they reduce the effectiveness of drugs. In addition, with the recent increase in alcohol intake, alcoholic liver disorder caused by alcohol intake is also a problem. In view of this, there is a need for development of an agent for reducing liver disorders that is more effective than before.

한편, 종래부터 인공적으로 합성된 화학품을 피하여, 보다 안전한 천연성분과 간기능과의 관계에 대해서 검토를 진행한 결과, 예를 들어 난(蘭)과 슈스란속의 다년생 약초식물인 미야마우즈라에서 채취한 성분을 유효성분으로 하는 간장애 억제제(특허공개 2000-16946호 공보)나 건조된 버섯균계의 체추출물을 포함한 약물에 의한 간장애의 억제제(특허공개 2000-159683호 공보) 등이 개발되고 있다. 그러나, 미각적으로 우수해지고 있을 뿐만 아니라 건강에 좋고, 각종 증상의 예방ㆍ개선을 도모할 수 있는 식품재료로부터 채취된 것으로서 간기능 개선에 우수한 재료를, 의식동원(醫食同源)을 고려하여 매일 섭취함으로써 간기능 장애의 예방, 간기능을 개선할 수 있기 때문에 바람직하다.On the other hand, by avoiding artificially synthesized chemicals and examining the relationship between safer natural ingredients and liver function, for example, they are collected from Miyama-Uzura, a perennial herbaceous plant of egg and Shussuran. Liver disorder inhibitors (Patent Publication No. 2000-16946) containing one component as an active ingredient, and inhibitors of liver disorders due to drugs including body extracts of dried mushroom fungi (Patent Publication No. 2000-159683) have been developed. . However, in consideration of the mobilization of consciousness, the foods are not only excellent in taste but also good for health, and are collected from food ingredients that can prevent and improve various symptoms. Daily intake is preferable because it can prevent liver failure and improve liver function.

이러한 관점에서, 식품재료와 생리적 기능과의 관련성에 대해서 연구한 결과, 미당 및 대두를 원료로 발효시켜서 얻어지는 발효추출물과 생리적 기능과의 관계에 대해서 다양한 발견이 이루어지고 있다. 예를 들어, 혈중 알콜농도 및 알콜구취를 저감시키는 미당ㆍ대두 발효추출물(일본국 특허공개 평 3-272657호 공보), 미당ㆍ대두발효 추출물을 포함한 활성효소억제 조성물, 및 이 발효추출물로이루어진 혈장 억제제(일본국 특허공개 평 6-284872호 공보, 동 6-315369호 공보), 미당ㆍ대두 발효추출물을 포함한 이뇨탈소취용 발효사료(일본국 특허공개 평 9-103252호 공보)등이 알려져 있다. 그러나, 상기 선행문헌에서는, 미당ㆍ대두 발효추출물과 알콜대사 반응과의 관계, 및 미당ㆍ대두 발효추출물과 간기능과의 관계에 대해서는 검토되어 있지 않다.From this point of view, as a result of studying the relationship between food ingredients and physiological functions, various findings have been made regarding the relationship between fermentation extract obtained by fermenting unsweetened sugar and soybean as raw materials. For example, an active enzyme-inhibiting composition including an unsweetened sugar and soybean fermented extract (Japanese Patent Laid-Open No. 3-272657), an unsweetened sugar and soybean fermented extract, which reduces blood alcohol concentration and alcohol odor, and plasma formed from the fermented extract Inhibitors (Japanese Patent Laid-Open No. 6-284872, Japanese Patent Laid-Open No. 6-315369), fermented feed for diuretic deodorization and deodorization, including unsweetened and soybean fermented extracts (Japanese Patent Laid-Open No. Hei 9-103252) are known. However, in the above-mentioned prior documents, the relationship between the sugar and soybean fermented extract and the alcohol metabolism reaction, and the relationship between the sugar and soybean fermented extract and the liver function have not been examined.

본 발명은 상기 현상을 감안하여 이루어진 것으로서, 생체내에서 안전하고 우수한 알콜대사 향상작용을 나타내는 알콜대사 향상제, 및 간장애, 특히 알콜이나 사염화탄소 등의 할로겐화합물에 기인하는 간장애의 저감작용을 나타내는 간장애저감제를 제공하는 것을 목적으로 한다.SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned phenomenon, and has been shown to reduce the liver metabolism due to an alcohol metabolism improving agent which shows a safe and excellent alcohol metabolism improving effect in vivo, and a liver compound caused by a halogen compound such as alcohol or carbon tetrachloride. It aims to provide a disability reducing agent.

도1은 실시예1에서, (a)는 혈청 GOT와 시간과의 관계를 나타내는 그래프이며, (b)는 혈청 GMT와 시간과의 관계를 나타내는 그래프이다.1 is a graph showing the relationship between serum GOT and time in Example 1, and (b) is a graph showing the relationship between serum GMT and time.

도2는 실시예1에서, (a)는 혈중 에탄올과 시간과의 관계를 나타내는 그래프이며, (b) 는 혈중 아세트알데히드와 시간과의 관계를 나타내는 그래프이다.2 is a graph showing the relationship between blood ethanol and time in Example 1, and (b) is a graph showing the relationship between acetaldehyde and time in blood.

도3은 실시예1에서, 간장 ADH 활성 및 ALDH 활성의 시험결과를 나타내는 그래프이다.Figure 3 is a graph showing the test results of hepatic ADH activity and ALDH activity in Example 1.

도4는 실시예2에서 ① 대조군, ② 사염화탄소군, 및 ③ 사염화탄소/GMT군의 GOT 활성 및 GPT 활성(IU/L)을 나타내는 그래프이다.4 is a graph showing GOT activity and GPT activity (IU / L) of ① control group, ② carbon tetrachloride group, and ③ carbon tetrachloride / GMT group in Example 2. FIG.

도5는 실시예2에서 ① 대조군, ② 사염화탄소군, 및 ③ 사염화탄소/GMT군의간장의 과산화지질(LPO)농도(nmol/g Liver)를 나타내는 그래프이다.Figure 5 is a graph showing the lipid peroxide (LPO) concentration (nmol / g Liver) of the liver of ① control group, ② carbon tetrachloride group, and ③ carbon tetrachloride / GMT group in Example 2.

본 발명자들은 상기 실정을 감안하여, 발효원료로 천연재료를 사용한, 안전한 발효물의, 알콜대사 및 간기능에 대한 영향에 대해서 다양하게 검토한 결과, 미당ㆍ대두 발효추출물에 알콜대사 향상작용 및 간장애 저감작용, 특히 알콜이나 사염화탄소 등의 할로겐화합물에 기인하는 간장애의 저감작용이 있는 것을 새롭게 발견하고, 본 발명을 완성하였다.In view of the above circumstances, the present inventors have conducted various studies on the effects of safe fermentation products, alcohol metabolism and liver function using natural ingredients as fermentation raw materials. The present inventors have newly discovered that there is a reducing action, in particular, a reducing action of liver failure caused by halogen compounds such as alcohol and carbon tetrachloride, and completed the present invention.

청구항1에 기재된 알콜대사 향상제 및 청구항2에 기재된 알콜 간장애 저감제는 미당류, 대두류 및 탄소원을 포함한 배지에 납두(納豆)균 또는 고초(枯草)균을 접종하고, 발효배양하여 얻어진 미당ㆍ대두 발효추출물을 함유하는 것을 특징으로 한다.The alcohol metabolism improving agent according to claim 1 and the alcohol hepatic disorder reducing agent according to claim 2 are obtained by inoculating a medium containing microsaccharides, soybeans, and a carbon source, inoculated with Bacteria or Bacillus subtilis and fermented culture. It is characterized by containing soybean fermented extract.

상기 「미당ㆍ대두 발효추출물」로는, 미당류, 대두류 및 탄소원을 포함한 배지에 납두균 또는 고초균을 접종하고, 발효배양하여 얻어지는 추출물이다. 상기 「미당ㆍ대두 발효추출물」로는, 배양하여 얻어진 배양발효액을 여과한 자체의 액이어도 좋지만, 이것에 탈색 등의 후처리를 행한 액이어도 좋고, 또한 이것을 농축한 농축액이어도 좋다. 이외에도, 분무건조 등의 공지된 방법으로 용매를 제거한 고형물이나 분말화한 분말물이어도 좋다.The "sugar sugar and soybean fermentation extract" is an extract obtained by inoculating a Bacillus subtilis or Bacillus subtilis in a medium containing unsaccharides, soybeans and a carbon source, and fermentation culture. The "sweetened soybean fermented extract" may be a liquid obtained by culturing the culture fermentation broth obtained by culturing, but may be a solution which has been subjected to post-treatment such as decolorization, or a concentrated solution obtained by concentrating it. In addition, it may be a solid or powdered powder in which the solvent is removed by a known method such as spray drying.

상기 「미당류」로는, 미(米)배아, 탈지 미배아, 미당, 탈지미당 등이 있으며, 상기 「대두류」로는, 탈지대두, 콩가루, 대두분, 대두앙금, 이들의 가수분해물 등이 있다. 또한, 상기 「탄소원」으로는, 일반적으로 사용되는 것을 사용할 수있는데, 예를 들어 굴루코스, 덱스트린, 유당 및 아밀로이드 등의 1종 또는 2종 이상을 사용할 수 있다. 일반적으로, 이들의 첨가비율은 미당류를 100 중량부로 하는 경우, 대두류가 1~20중량부, 바람직하게는 10~20중량부이며, 탄소원은 20~80중량부, 바람직하게는 40~60중량부이다. 이러한 범위에 있으면, 균의 발육에 가장 바람직하다.Examples of the "sugars" include rice embryos, non-fat embryos, microsaccharides, and skim sugars. The soybeans include skim soybeans, soy flour, soy flour, soybean flour, and hydrolysates thereof. . Moreover, as said "carbon source", what is generally used can be used, For example, 1 type (s) or 2 or more types, such as a gurucose, dextrin, lactose, an amyloid, can be used. Generally, these addition ratios are 1 to 20 parts by weight, preferably 10 to 20 parts by weight, and 20 to 80 parts by weight, preferably 40 to 60 parts of soybeans, when 100 parts by weight of unsaccharides is used. Parts by weight. If it exists in this range, it is the most preferable for the growth of bacteria.

상기 「배지」로는, 상기 미당류, 대두류 및 탄소원을 포함하여, 납두균 또는 고초균이 증식할 수 있는 것이기만 하면 특별히 한정되지 않는데, 일반적으로는 물에 미당류, 대두류 및 탄소원을 첨가한 액체배지가 사용된다. 또한, 상기 「배지」는 일반적으로는 액체배지이지만, 고형배지여도 상관없다.The "medium" is not particularly limited as long as the Bacillus or Bacillus subtilis, including the unsaccharides, soybeans, and carbon sources, can grow, but generally a liquid in which unsaccharides, soybeans, and carbon sources are added to water. Medium is used. In addition, although the said "medium" is generally a liquid medium, it may be a solid medium.

그리고, 상기 「납두균」및 「고초균」은 시판되고 있는 일반적인 납두균이나 고초균을 사용하는 것이 일반적이다. 그러나, 자연적이거나 니트로소구아니딘 등의 화학물질, 엑스선, 자외선 등에 의한 인위적 변이수단에 의해 얻어지는, 균학적 성질이 변이된 납두균이나 고초균의 변이주여도, 알콜대사 향상작용 또는 간장애 저감작용을 보유하는 미당ㆍ대두 발효추출물을 생성하는 성질을 잃지 않는 한 이용할 수 있다.In addition, it is common to use the commercially available general Ba Streptococcus and Bacillus subtilis as said "naptobacilli" and "Bacillus subtilis". However, even if the natural or mutated strains of Bacillus or Bacillus subtilis obtained by artificial mutagenesis by chemical substances such as nitrosoguanidine, X-rays, ultraviolet rays, etc., have the effect of improving alcohol metabolism or reducing liver disorders. It can be used as long as it does not lose the property of producing sweetened sugar and soybean fermented extract.

일반적으로 발효배양은 통기교반을 행함으로써 실시된다. 이 발효배양 조건은 발효가 행해지는 한 특히 한정되지는 않지만, 통상 pH가 7.5~10, 바람직하게는 8.5~10이며, 배양온도는 40~45℃ 정도이다. 배지의 pH를 조정하는 경우는, 알칼리제로 탄산수소나트륨 등을 사용할 수 있다. 또, 배지원료로는 프로테아제를 사용할 수 있다. 이 경우는, 대두펩티드를 더 분해하기 때문에 유용하다. 또한, 발효배양하기 전에, 원료인 미당ㆍ대두에 대해서, 산성조건하에서 유산균으로 발효시키는 등의 전발효를 함으로써, 우수한 미당ㆍ대두 발효추출물이 얻어지기 때문에 바람직하다.In general, fermentation culture is carried out by aeration stirring. This fermentation culture condition is not particularly limited as long as fermentation is carried out, but pH is usually 7.5-10, preferably 8.5-10, the culture temperature is about 40 ~ 45 ℃. When adjusting pH of a medium, sodium hydrogencarbonate etc. can be used as an alkali chemicals. In addition, a protease can be used as a medium raw material. This case is useful because it further decomposes the soybean peptide. In addition, before fermentation culture, excellent microsaccharides / soybean fermentation extracts are obtained by prefermentation such as fermentation of lactobacillus under acidic conditions with crude sugars and soybeans as raw materials.

본 발명의 미당ㆍ대두 발효추출물은, 예를 들어 이하의 방법으로 제조할 수 있다. 즉, 배지원료로 탈지미당을 30.0kg, 탈지대두를 5.0kg, 휘틴산을 5.0kg, 글루코스를 15.0kg, 인산이수소나트륨을 10.0kg, 인산수소이암모늄을 2.5kg, 탄산수소나트륨을 45.0kg, 소포제를 0.25kg, 물을 500kg 사용한다. 또, pH는 9전후이다. 이 배지를 121℃, 30분에서 살균하고, 그 후 냉각하고 나서, 납두균(제조원; 성뢰성(成瀨) 발효화학 연구소) 0.05kg을 접종하고, 40~45℃에서 약 48시간, 통기, 교반하여 배양시켜서 배양물을 얻는다. 이후, 이 배양물을 압착여과하고, 활성탄 및 할라이드로 처리하여 탈취, 탈색하고, 거의 투명한 미당ㆍ대두 발효추출 엑기스를 얻는다(고형분 농도; 5중량% 정도). 또, 이 활성탄으로는, 분말활성탄(활성탄S, 활성탄K 등), 입상 활성탄(활성탄SG 등)의 다양한 것을 사용할 수 있으며, 할라이드로는 「할라이드 No. 4180」(다이카라인 오리엔트 주식회사 제품)을 사용할 수 있다.The unsweetened soybean fermented extract of the present invention can be produced, for example, by the following method. That is, as raw materials, 30.0 kg of skim sugar, 5.0 kg of defatted soybean, 5.0 kg of phytic acid, glucose 15.0 kg, 10.0 kg of sodium dihydrogen phosphate, 2.5 kg of diammonium phosphate, 45.0 kg of sodium bicarbonate, 0.25 kg of antifoam and 500 kg of water are used. In addition, pH is around nine. The medium was sterilized at 121 ° C. for 30 minutes, and then cooled, and then inoculated with 0.05 kg of Bacillus aeruginosa (manufactured by a tolerant fermentation chemical research institute), and then aerated and agitated at 40 to 45 ° C. for about 48 hours. Culture to obtain a culture. Then, the culture is compressed and filtered, treated with activated carbon and halide to deodorize and decolorize to obtain an almost transparent microsaccharide / soybean fermentation extract (solid content: about 5% by weight). As the activated carbon, various kinds of powdered activated carbon (activated carbon S, activated carbon K, etc.) and granular activated carbon (activated carbon SG, etc.) can be used. 4180 ”(made by Daika Orient Co., Ltd.) can be used.

청구항 2항에 기재된 간장애 저감제는 각종 간장애의 치료, 개선 등에 널리 사용될 수 있다. 예를 들어, ① 항생물질(페니실린계, 세펨계, 아미노배당체계, 아크랄루비신 등의 항종양계, 리팜피신 등의 항산균 항생물질계, 테트라사이클린계, 머크롤라이드계 등), 해열진통약(아스피린, 아세트아미노펜 등) 등에 기인하는 세포장애형 간장애나, ② 모노아민옥시다아제 저해제(히드라진 유도체[이프로니아지드 등]), 전신 마취약(하로탄, 엔플루란, 이소플루란 등), 설파제(설파메톡사졸, 사라조설파피리딘 등), 항결핵약(히드라진계[피라지나미드, 이소니아지드, 에티오나미드, PAS 등]) 등에 기인하는 간염형 간장애, ③ 기타, 클로로포름, 사염화탄소, 비스페놀, 프탈산에스테르, 염화물, 알킬페놀, 알콜류 등에 기인하는 간장애, 간염바이러스 등의 감염에 의한 간장애에 유용하다.The liver disorder reducing agent according to claim 2 can be widely used for the treatment and improvement of various liver disorders. For example, ① antibiotics (penicillin system, cefem system, amino glycoside system, antitumor system such as acrorubicin, antibacterial antibiotic system such as rifampicin, tetracycline system, mercuride system, etc.), antipyretic analgesics (aspirin , Cell disorders caused by acetaminophen, etc.), ② monoamine oxidase inhibitors (hydrazine derivatives [iproniazide, etc.)), general anesthetics (harlotane, enflurane, isoflurane, etc.), sulfases (sulfamethok) Hepatitis-based liver disorders caused by azoles, sarazosulfapiridine, etc.) and anti-tuberculosis drugs (pyrazinide [pyrazinamide, isoniazid, ethionamide, PAS, etc.]), and others, chloroform, carbon tetrachloride, bisphenol, phthalate ester, It is useful for liver disorders caused by chlorides, alkylphenols, alcohols and the like, and liver disorders caused by infections of hepatitis virus.

특히, 청구항 2항에 기재된 간장애 저감제는, 알콜 유발성 간장애 및 할로겐계 화합물 유발성 간장애에 효과적이기 때문에, 청구항 3항에 기재된 알콜 유발성 간장애 저감제 및 청구항 4항에 기재된 할로겐계 화합물 유발성 간장애 저감제로 바람직하게 사용할 수 있다. 상기 할로겐화합물로는, 예를 들어 사염화탄소, 클로로포름, 할로겐계 흡입 전신마취약(하로탄, 엔플루란, 이소플루란 등) 등이 있으며, 이중에서 청구항 5항에 기재된 대로, 특히 사염화탄소 유발성 간장애에 대하여 바람직하게 사용할 수 있다.In particular, since the liver disorder reducing agent according to claim 2 is effective for alcohol-induced liver disorder and halogen-based compound-induced liver disorder, the alcohol-induced liver disorder reducing agent according to claim 3 and the halogen according to claim 4 It can be preferably used as a system compound-induced liver disorder reducing agent. The halogen compounds include, for example, carbon tetrachloride, chloroform, halogen-based inhalation general anesthetics (harotan, enfluran, isoflurane, etc.), among others, as described in claim 5, in particular carbon tetrachloride-induced liver disorders. It can be used preferably.

이하, 실시예에 의해 본 발명을 상세하게 설명한다.Hereinafter, an Example demonstrates this invention in detail.

(A) 대두ㆍ미당 발효추출물의 제조(A) Preparation of Soybean and Unsweetened Fermented Extract

탈지미당 30g, 탈지대두 5g, 글루코스 0.3g에 물 약 350㎖를 첨가하고, 탄산나트륨으로 pH가 9.0이 되도록 조정한 다음, 전량이 500g이 되도록 물을 첨가하였다. 90℃에서 10분간 가열한 다음 냉각하여 납두균(「납두소」고교 우장(祐臟) 연구소) 5㎖를 첨가하였다. 특히 강제통기시키지 않고, 42℃에서 18시간 교반하였다. 그 후, 90℃에서 10분간 가열하고, 냉각후 여과(여과조제로 할라이드를 사용함)하여 미당ㆍ대두 발효추출물(「GMT」라고 함. 고형분농도; 5중량%)을 얻었다.About 350 ml of water was added to 30 g of degreasing rice, 5 g of defatted soybean, and 0.3 g of glucose, and adjusted to pH 9.0 with sodium carbonate, and then water was added so that the total amount was 500 g. After heating at 90 ° C. for 10 minutes, the mixture was cooled, and 5 ml of Naphtha bacteria (“Naduso High School Beef Lab.”) Was added. In particular, it stirred at 42 degreeC for 18 hours, without forcing aeration. Thereafter, the mixture was heated at 90 DEG C for 10 minutes, and then cooled and filtered (using halide as a filtration aid) to obtain a sugar-free or soybean fermented extract (referred to as "GMT", solid content concentration: 5% by weight).

(B) 실험동물 및 사육방법(B) Experimental animals and breeding methods

이하의 실시예1에서, 10주된 SD계 수컷 래트(SLC 주식회사)를 고형사료(오리엔탈 효모 공업주식회사)로 1주간 예비사육한 다음, 시험용으로 하였다. 또한, 실시예2에서는 ddY계의 6주된 수컷 마우스(오리엔탈 효모 공업 주식회사 제)를 고형사료(오리엔탈 효모 공업 주식회사 제품)로 1주간 예비사육한 다음, 시험용으로 하였다. 또, 예비사육 및 시험기간중에는, 실시예1 및 실시예2를 실온 25 ±1℃, 습도 50 ±5%, 명암 12시간 주기로 하였다.In Example 1 below, 10-week-old male SD rats (SLC Co., Ltd.) were preliminarily bred with solid feed (Oriental Yeast Industrial Co., Ltd.) for 1 week, and then used for testing. In Example 2, six-week-old male mice (Oriental Yeast Industrial Co., Ltd.) of ddY series were preliminarily bred with solid feed (Oriental Yeast Industrial Co., Ltd.) for one week, and then used for testing. In the preliminary breeding and testing periods, Examples 1 and 2 were set to a cycle of 25 ± 1 ° C, a humidity of 50 ± 5%, and a contrast of 12 hours.

(C)실시예(C) Example

[실시예1]Example 1

(1) 알콜부하 실험(1) alcohol load test

상기 (B)의 래트를 이하, 즉 ① 대조군(증류수), ② EtOH군(증류수), 및 ③ EtOH/GMT군(0.12% GMT)의 3군으로 분류하였다. 에탄올 투여군에 표1에 표시한 대로 시험사료와, 15% 에탄올 용액으로 에탄올 1.0g/kg, BW/day를 강제 경구투여하였다. 음용수로 증류수 또는 공시샘플 용액을 사용하고, 각 군 6마리, 시험주간을 30일간으로 하고, 사료 및 음용수는 자유롭게 섭취시켰다. 또, 대조군에는 알콜 파우더 대신에 수크로오스 파우더를 사용하고, 15% 에탄올 용액 대신에 증류수를 강제 경구투여하였다.Rats of (B) were classified into the following three groups: ① control group (distilled water), ② EtOH group (distilled water), and ③ EtOH / GMT group (0.12% GMT). As shown in Table 1, the ethanol administered group was orally administered 1.0 g / kg of ethanol and BW / day with 15% ethanol solution. Distilled water or a test sample solution was used as drinking water, and 6 animals of each group and the test week were made for 30 days, and feed and drinking water were ingested freely. In addition, as a control, sucrose powder was used instead of alcohol powder, and distilled water was forcibly administered orally instead of 15% ethanol solution.

알콜함유 시험사료의 조성Composition of Test Feeds Containing Alcohol 원료Raw material 배합비율(%)Compounding ratio (%) 단백질(PEP)Protein (PEP) 15.015.0 설당Snow 13.013.0 대두유Soybean oil 6.06.0 셀룰로오스 파우더Cellulose powder 8.08.0 혼합 비타민Mixed vitamins 2.02.0 혼합 미네랄Mixed minerals 6.06.0 알콜 파우더Alcohol powder 50.050.0 합계Sum 100.0100.0

1; 정제 전란 단백질(큐우피이 주식회사 제품)One; Purified whole egg protein (from Kewpie Co., Ltd.)

2; 오리엔탈 믹스(오리엔탈 효모 공업 주식회사 제품)2; Oriental Mix (Oriental Yeast Industry Co., Ltd. product)

3; 알콜 함량 30.5%(좌등(佐藤) 식품공업 주식회사 제품)3; Alcohol content 30.5% (product made by Left Light Food Industry Co., Ltd.)

(2) GOT 및 GPT 활성(2) GOT and GPT activity

시험개시 0, 10, 20 및 30일 후에 채혈하여, 글루타민산ㆍ옥사로초산ㆍ트랜스아미나아제(GOT) 활성 및 글루타민산ㆍ피루빈산ㆍ트랜스아미나아제(GPT) 활성을 측정하였다. 측정은, 시판성 화학검사용 효소키트[트랜스아미나아제 CII 테스트와코(화광 순약 주식회사 제품)]을 사용하였다. 이것의 결과를 표2 및 도1에 표시한다.Blood was collected at 0, 10, 20, and 30 days after the start of the test, and glutamic acid, oxaroacetic acid, transaminase (GOT) activity and glutamic acid, pyruvic acid, and transaminase (GPT) activity were measured. The measurement used the enzyme kit for commercial chemistry test (transaminase CII test Wako (made by Hwagwang Pure Chemical Co., Ltd.)). The results are shown in Table 2 and FIG.

혈청 GOT 및 GPT활성에 미치는 GMT 섭취의 영향Effect of GMT Intake on Serum GOT and GPT Activity 일수Days GOTGOT GPTGPT 대조contrast EtOHEtOH EtOH/GMTEtOH / GMT 대조contrast EtOHEtOH EtOH/GMTEtOH / GMT 00 46.3 ±4.146.3 ± 4.1 45.1 ±3.945.1 ± 3.9 44.9 ±4.344.9 ± 4.3 22.4±2.422.4 ± 2.4 22.0 ±2.222.0 ± 2.2 21.3 ±2.621.3 ± 2.6 1010 50.6 ±3.550.6 ± 3.5 92.5 ±11.392.5 ± 11.3 65.7 ±6.665.7 ± 6.6 22.0±1.822.0 ± 1.8 53.2 ±4.653.2 ± 4.6 25.9 ±2.025.9 ± 2.0 2020 58.1 ±4.658.1 ± 4.6 103.3 ±8.6103.3 ± 8.6 70.1 ±7.170.1 ± 7.1 23.9 ±4.923.9 ± 4.9 60.6 ±5.160.6 ± 5.1 35.8 ±1.835.8 ± 1.8 3030 56.2 ±5.156.2 ± 5.1 130.6 ±10.1130.6 ± 10.1 70.7 ±5.370.7 ± 5.3 19.8 ±2.219.8 ± 2.2 72.3 ±6.472.3 ± 6.4 41.1 ±4.741.1 ± 4.7

(3) 알콜대사시험(3) Alcohol metabolism test

시험 24일째, 2시간동안 음식을 주지 않은 다음, 대조군 및 EtOH군에는 증류수를, EtOH/GMT군에는 GMT 0.2g/kg BW를 각각 강제 경구투여하였다. 30분후, 15% 에탄올 용액으로 에탄올 1.0g/kg BW/day를 강제 경구투여하고, 에탄올 투여 후 30분, 1 및 6시간이 지나서 채혈하여 혈중 에탄올 및 아세트알데히드를 측정하였다. 측정은, 시판측정용 키트(F-키트 에탄올, F-키트 아세트알데히드(베링거ㆍ맨하임 주식회사)를 사용하였다. 이것의 결과를 표3 및 도2에 표시한다.On the 24th day of the test, no food was given for 2 hours, followed by forced oral administration of distilled water to the control group and the EtOH group, and 0.2 g / kg BW of the GMT to the EtOH / GMT group. After 30 minutes, 1.0 g / kg BW / day of ethanol was forcibly administered orally with 15% ethanol solution, and blood ethanol and acetaldehyde were measured by collecting blood 30 minutes, 1 and 6 hours after ethanol administration. The measurement used commercially available measurement kits (F-kit ethanol and F-kit acetaldehyde (Behringer-Manheim Co., Ltd.). The results are shown in Table 3 and FIG.

혈중 에탄올 및 아세트알데히드 농도에 미치는 GMT 섭취의 영향Effect of GMT Uptake on Blood Ethanol and Acetaldehyde Concentrations 시간(h)Hours (h) 에탄올(mg/L)Ethanol (mg / L) 아세트알데히드(mg/L)Acetaldehyde (mg / L) 대조contrast EtOHEtOH EtOH/GMTEtOH / GMT 대조contrast EtOHEtOH EtOH/GMTEtOH / GMT 00 00 00 00 00 7.5 ±2.37.5 ± 2.3 4.6 ±1.54.6 ± 1.5 0.50.5 796 ±65.3796 ± 65.3 821 ±76.1821 ± 76.1 716 ±75.6716 ± 75.6 30.1 ±1.330.1 ± 1.3 31.6 ±1.531.6 ± 1.5 27.7 ±3.027.7 ± 3.0 1.01.0 717 ±38.8717 ± 38.8 790 ±81.8790 ± 81.8 581 ±55.5581 ± 55.5 23.5 ±2.123.5 ± 2.1 26.3 ±1.926.3 ± 1.9 19.2 ±1.319.2 ± 1.3 6.06.0 55 ±4.655 ± 4.6 104 ±46.3104 ± 46.3 11 ±8.611 ± 8.6 5.0 ±2.65.0 ± 2.6 9.6 ±4.19.6 ± 4.1 2.3 ±1.12.3 ± 1.1

(4) ADH 및 ALDH 활성(4) ADH and ALDH activity

시험 30일째, 12시간 음식을 주지 않은 다음, 15% 에탄올 용액으로, 에탄올 1.0g/kg BW/day를 강제 경구투여하고, 30분후에 간장을 채취하였다. 간장 0.5g에 0.25M-수크로오스, 2mM-머캅토에탄올을 포함한 10mM 인산나트륨 완충액(pH 7.4) 2㎖를 첨가하고, 균질화액을 제조하였다. 700 ×g, 5분 동안 원심분리한 다음, 그것의 상청액을 다시 450 ×g, 10분 동안 원심분리하였다. 얻어진 침전에 마찬가지로 10mM의 인산나트륨 완충액(pH 7.4) 2㎖를 첨가하여 현탁한 다음, 동일한 조작을 반복하여 침전물을 얻었다. 간장샘플의 2배량의 0.15M-KC1(0.3%-콜산나트륨을 포함함)을 첨가하여 현탁하고 나서, 106000 ×g, 60분 동안 원심분리하고, 그것의 상청액을 알콜디히드로게나아제(ADH) 및 아세트알데히드디히드로게아나제(ALDH) 활성측정용 시료로 하였다.On the 30th day of the test, after 12 hours without food, 1.0 g / kg BW / day of ethanol was forcibly administered orally with 15% ethanol solution, and the liver was collected 30 minutes later. To 0.5 g of soy sauce, 2 ml of 10 mM sodium phosphate buffer (pH 7.4) containing 0.25 M sucrose and 2 mM mercaptoethanol was added, and a homogenate was prepared. 700 × g, centrifuged for 5 minutes, then its supernatant was again centrifuged for 450 × g, 10 minutes. Similarly, 2 ml of 10 mM sodium phosphate buffer (pH 7.4) was added to the obtained precipitate and suspended, and the same operation was repeated to obtain a precipitate. Suspension was added by adding twice the amount of soy sauce 0.15M-KC1 (containing 0.3% sodium sodium cholate), centrifuged for 106000 xg, 60 minutes, and the supernatant thereof was dehydrogenase (ADH). And a sample for measuring acetaldehyde dehydrogenase (ALDH) activity.

ADH 활성 측정반응 조성은, 3M-에탄올: 0.1㎖, 0.06M-피롤린산나트륨 완충액(pH 8.5):0.5㎖, 1.5mM-NAD+: 0.1㎖, H2O: 2.2㎖로 하였다. 또한, ALDH 활성측정 반응 조성은 5mM- 아세트알데히드: 0.1㎖, 0.05M-피롤린산나트륨 완충액(pH 8.8): 0.5㎖, 1mM-NAD+: 0.1㎖, 0.1mM-피라졸: 0.1㎖, 2μM-로테논(MeOH로): 0.1㎖, H2O: 2㎖로 하였다.ADH activity measurement reaction composition, 3M- ethanol: To a 2.2㎖: 0.1㎖, 0.06M- sodium pyrophosphate buffer (pH 8.5): 0.5㎖, 1.5mM -NAD +: 0.1㎖, H 2 O. In addition, the ALDH activity measurement reaction composition was 5 mM acetaldehyde: 0.1 ml, 0.05 M sodium pyrrolate buffer (pH 8.8): 0.5 ml, 1 mM-NAD + : 0.1 ml, 0.1 mM-pyrazole: 0.1 ml, 2 µM- (in MeOH) non Rotterdam: to a 2㎖: 0.1㎖, H 2 O.

25℃에서 샘플 0.1㎖를 첨가함으로써 반응을 개시하고, 340nm의 흡광도에 의해 1분당 NADH의 생성량으로 활성을 측정하였다. 단백질의 정량은 Lowry의 방법을 따랐다. 그 결과를 표4 및 도3에 표시한다.The reaction was started by adding 0.1 ml of the sample at 25 ° C, and the activity was measured by the amount of NADH produced per minute by absorbance at 340 nm. Protein quantitation was followed by Lowry's method. The results are shown in Table 4 and FIG.

간장 ADH 및 ALDH 활성에 미치는 GMT섭취의 영향Effect of GMT Intake on Hepatic ADH and ALDH Activity 대조contrast EtOHEtOH EtOH/GMTEtOH / GMT ADH(nmol/min/mg 단백질)ADH (nmol / min / mg protein) 15.6 ±4.215.6 ± 4.2 11.2 ±1.311.2 ± 1.3 23.3 ±6.523.3 ± 6.5 ALDH(nmol/min/mg 단백질)ALDH (nmol / min / mg protein) 13.6 ±2.613.6 ± 2.6 8.5 ±1.38.5 ± 1.3 17.6 ±4.017.6 ± 4.0

[실시예2]Example 2

(1) 사염화탄소의 투여(1) Administration of carbon tetrachloride

상기 (B)의 마우스를 18시간 동안 음식을 주지 않은 다음, 마우스 각 군의 평균체중이 균일하게 되도록, ① 대조군, ② 사염화탄소군, 및 ③사염화탄소군/GMT군의 3군으로 분리하였다. 또, 1군당 마우스는 10마리이다. 그리고, ① 대조군 및 ② 사염화탄소군에는 증류수를, ③ 사염화탄소군/GMT군에는 상기 (A)에서 제조한 GMT 0.4g/kg BW를 각각 경구투여로 주입하였다. 30분후, ② 사염화탄소군 및 ③ 사염화탄소군/GMT군에는, 1%의 사염화탄소로 사염화탄소 0.1g/kg BW를 복강내 투여하였다. 한편, ① 대조군에는, 사염화탄소의 희석에 사용된 단쇄 지방산 중성 지방인 파나셋을 투여하였다. 사염화탄소를 투여한 시점에서 24시간 경과한 후에 넨프탈로 마취한 가운데, 마우스로부터 혈액 및 간장을 채취하고, 혈액은 바로 혈청분리를 한 다음, 트랜스아미나아제 활성을 측정하는데 사용하였다. 또한, 간장은 0.9%의 생리식염수로 세정한 후, 분석까지 -80℃에서 동결보존하였다.The mice of (B) were not fed for 18 hours, and then divided into three groups: ① control group, ② carbon tetrachloride group, and ③ carbon tetrachloride group / GMT group so that the average weight of each group was uniform. In addition, there are 10 mice per group. Then, ① control group and ② carbon tetrachloride group was injected with distilled water, ③ carbon tetrachloride group / GMT group was injected with oral administration of 0.4 g / kg BW of GMT prepared in the above (A). After 30 minutes, the carbon tetrachloride group and the carbon tetrachloride group / GMT group were intraperitoneally administered with 0.1 g / kg BW of carbon tetrachloride at 1% carbon tetrachloride. Meanwhile, ① control group was administered panacet, a short-chain fatty acid neutral fat used for dilution of carbon tetrachloride. 24 hours after the time of administration of carbon tetrachloride, blood and liver were collected from the mouse while anesthetized with enephthal, and the blood was immediately serum-separated and used for measuring transaminase activity. Soy sauce was washed with 0.9% saline and then cryopreserved at -80 ° C until analysis.

(2) 트랜스아미나아제 활성(2) transaminase activity

트랜스아미나아제 활성으로, GOT 활성 및 GPT 활성을 측정하였다. 측정은, 시판되는 생화학 검사용 효소키트(화광 순약 주식회사 제품, 「트랜스아미나아제 CII 테스트와코」)를 사용하여, 키트에 기재된 순서로 행하였다. 그 결과를 이하의 표5 및 도4에 표시한다.With transaminase activity, GOT activity and GPT activity were measured. The measurement was performed in the procedure described in the kit using the commercially available enzyme kit for biochemical test ("Transaminase CII test Wako" by Hwagwang Pure Chemical Co., Ltd.). The results are shown in Table 5 below and FIG.

(3) 간장 과산화지질(LPO)의 측정(3) Measurement of Soy Lipid Peroxide (LPO)

상기 마우스의 LPO를, 티오바르비탈산(이하, 「TBA」라고 함) 반응을 사용하여, 마론디알데히드로 정량하는 팔목법에 의해 측정하였다. 상기 (1)에서 채취한 마우스의 간장에 1.15% 염화칼륨을 첨가하고 30% 균질화액을 제조하여 LPO 측정용 샘플로 하였다. 그리고, 상기 LPO 측정용 샘플 0.1㎖, 8.1% 도데실황산나트륨 0.2㎖, 초산 완충액(pH 3.5) 1.5㎖, 0.8% BHT 빙초산용액 0.05㎖, 0.8% TBA 1.5㎖, 및5mM EDTA 0.7㎖를 이 순서로 첨가하고, 충분히 혼합하여 혼합액을 제조하였다. 그후, 혼합액을 5℃에서 60분간 방치하였다. 다음으로, 상기 혼합액을 비등수욕중에서 60분간 가열하고, 냉각한 다음 물 1.0㎖ 및 부탄올-피리딘 혼합액(15:1) 5.0㎖를 첨가하여 충분히 혼합하였다. 그리고 나서, 3000rpm에서 10분간 원심분리한 다음, 상청액을 채취하고, 이 상청액의 532nm에서 흡광도를 측정하여 LPO를 측정하였다. 그 결과를 표5 및 도5에 표시한다.LPO of the mouse was measured by the cuff method of quantifying marondialdehyde using a thiobarbital acid (hereinafter referred to as "TBA") reaction. 1.15% potassium chloride was added to the liver of the mouse collected in the above (1), and a 30% homogenized solution was prepared as a sample for measuring LPO. In this order, 0.1 ml of the LPO measurement sample, 0.2 ml of 8.1% dodecyl sulfate, 1.5 ml of acetic acid buffer (pH 3.5), 0.05 ml of 0.8% BHT glacial acetic acid solution, 0.8 ml of 0.8% TBA, and 0.7 ml of 5 mM EDTA in this order. It was added and mixed sufficiently to prepare a mixed liquid. Thereafter, the mixed solution was allowed to stand at 5 ° C for 60 minutes. Next, the mixed solution was heated in a boiling water bath for 60 minutes, cooled, and sufficiently mixed with 1.0 ml of water and 5.0 ml of butanol-pyridine mixed solution (15: 1). Then, after centrifugation at 3000 rpm for 10 minutes, the supernatant was collected, and the absorbance was measured at 532 nm of the supernatant to measure LPO. The results are shown in Table 5 and FIG.

GOT(IU/L)GOT (IU / L) GPT(IU/L)GPT (IU / L) LPO(nmol/g Liver)LPO (nmol / g Liver) 대조contrast 30.6 ±8.730.6 ± 8.7 17.0 ±10.517.0 ± 10.5 325.7 ±49.5325.7 ± 49.5 CCl4 CCl 4 3011.6 ±597.53011.6 ± 597.5 1659.8 ±398.11659.8 ± 398.1 1130.8 ±217.21130.8 ± 217.2 CCl4/GMTCCl 4 / GMT 1776.6 ±381.81776.6 ± 381.8 1061.8 ±224.81061.8 ± 224.8 771.4 ±96.4771.4 ± 96.4

(D) 실시예의 효과(D) Effect of Example

(1) 에탄올 투여와 혈청 GOT 및 GPT 활성(1) Ethanol Administration and Serum GOT and GPT Activity

표2 및 도1(a) 및 (b)에 표시한 대로, 에탄올 투여군(EtOH군 및 EtOH/GMT군)은, 에탄올 섭취에 따라 혈청 GOT 및 GPT활성값이 상승되는 것을 확인하였다. 한편, EtOH/GMT군의 혈청 GOT 및 GPT활성값이 상승은, EtOH군에 비해서 낮고, 대조군에 가까운 수준으로 되었다. 15주된 SD계 래트의 혈청 GOT 및 GPT 활성값의 정상범위는, 각각 33~94IU/L 및 15~34IU/L로 확인되었지만, EtOH/GMT군에 확인된 값은 거의 이 범위에 있었다. 이것으로부터, GMT는 에탄올 섭취에 따른 혈청 GOT 및 GPT 활성값이 상승하는 것을 억제하는 효과를 보유하고 있는 것이 확인되었다. 따라서, 이 GMT는 알콜에 의한 간기능장애를 억제할 수 있다는 것을 알 수 있다.As shown in Table 2 and FIGS. 1 (a) and (b), the ethanol administration group (EtOH group and EtOH / GMT group) confirmed that serum GOT and GPT activity values increased with ethanol intake. On the other hand, the increase in serum GOT and GPT activity values of the EtOH / GMT group was lower than that of the EtOH group and became a level close to the control group. Normal ranges of serum GOT and GPT activity values of 15-week-old SD rats were 33-94 IU / L and 15-34 IU / L, respectively, but the values identified in the EtOH / GMT group were almost in this range. From this, it was confirmed that GMT has an effect of suppressing the increase of serum GOT and GPT activity values due to ethanol intake. Therefore, it can be seen that this GMT can suppress liver dysfunction caused by alcohol.

(2) 혈중 에탄올 및 아세트알데히드 농도(2) blood ethanol and acetaldehyde concentration

표3 및 도2(a) 및 (b)에 표시한 대로, 어느 군도 에탄올 투여후 30분에서 혈중 에탄올 및 아세트알데히드 농도가 최고치를 나타내며, 6시간 후에는 거의 초기값까지 소실되어 있는 것을 확인하였다. EtOH/GMT군의 혈중 에탄올 및 아세트알데히드의 소실은 대조군 및 EtOH군의 그것에 비하여 빠르다는 것이 확인되었다. 즉, 혈중 에탄올 농도가 최대값의 약 절반(400mg/L)으로 되는 시간은 EtOH군의 3.8시간에 비해서, EtOH/GMT군이 2.6시간으로, 32%정도 단축된다. 또한, 혈중 알데히드 농도가 최대값의 약절반(15mg/L)으로 되는 시간은, EtOH군의 4.4시간에 비해서 EtOH/GMT군이 2.2시간으로, 100%정도 단축된다. 따라서, 이 GMT는 알콜에 의한 간기능 장애를 억제할 수 있다는 것을 알 수 있다.As shown in Table 3 and Figs. 2 (a) and (b), it was confirmed that blood ethanol and acetaldehyde concentration showed the highest value at 30 minutes after ethanol administration, and disappeared to the initial value after 6 hours. . It was confirmed that the loss of ethanol and acetaldehyde in blood of the EtOH / GMT group was faster than that of the control and EtOH groups. That is, the time when blood ethanol concentration becomes about half (400 mg / L) of the maximum value is shortened by 32% compared with 3.8 hours of EtOH group compared with 3.8 hours of EtOH group. In addition, the time at which the aldehyde concentration in blood reaches a maximum value of about half (15 mg / L) is shortened by about 100% in the EtOH / GMT group compared to 4.4 hours in the EtOH group. Thus, it can be seen that this GMT can suppress liver dysfunction caused by alcohol.

(3) 간장 ADH 및 ALDH 활성(3) hepatic ADH and ALDH activity

표4 및 도3에 표시한 대로, EtOH군의 간장 ADH 및 ALDH 활성은, 대조군에 비해서 낮았다. 그러나, EtOH/GMT군의 그것은 대조군에 비해서 유의하게 높고, GMT섭취에 의한, ADH 및 ALDH의 생합성 촉진 또는 활성화의 가능성이 확인되었다. 즉, EtOH/GMT군의 경우는, 알콜 대사 효소가 증대되고, 그 결과 알콜대사가 향상된다는 것이 확인되었으며, 그 때문에 알콜에 의한 간기능 장애를 억제할 수 있다.As shown in Table 4 and FIG. 3, the hepatic ADH and ALDH activities of the EtOH group were lower than those of the control group. However, in the EtOH / GMT group it was significantly higher than the control group, and the possibility of promoting or activating the biosynthesis of ADH and ALDH by GMT intake was confirmed. That is, in the case of the EtOH / GMT group, it was confirmed that the alcohol metabolizing enzyme is increased, and as a result, the alcohol metabolism is improved, and therefore, liver dysfunction by alcohol can be suppressed.

(4) 사염화탄소 투여와 혈청 GOT 및 GPT활성(4) Administration of carbon tetrachloride and serum GOT and GPT activity

혈청 트랜스아미나아제는 간장애의 정도를 나타내는 지료로 널리 사용되고 있으며, 수치가 높을수록 간장애가 크다는 것을 의미한다. 그리고, 표5 및 도4로부터, 사염화탄소를 투여하지 않은 ① 대조군과, 사염화탄소를 투여한 ② 사염화탄소군을 비교하면, GOT 및 GPT도 ② 사염화탄소군은 ① 대조군의 100배 전후의 값을 나타내기 때문에, ② 사염화탄소군에서는 간장애가 촉진되고 있다는 것을 알 수 있다. 한편, 사염화탄소만을 투여하고 있는 ② 사염화탄소군과, 사염화탄소 및 GMT 모두를 투여한 ③ 사염화탄소군/GMT군을 비교하면, GOT 및 GPT도 ③ 사염화탄소군/GMT군에서는 ② 사염화탄소군보다도 약 40% 정도 유의하게 저하된다는 것을 확인하였다.Serum transaminase is widely used as a material indicating the degree of liver disorder, and the higher the value, the greater the liver disorder. And, from Table 5 and Fig. 4, when comparing the ① control group not administered carbon tetrachloride to the carbon tetrachloride group ② administered with carbon tetrachloride, the GOT and GPT degrees ② the carbon tetrachloride group showed values around 100 times of the ① control group, ② carbon tetrachloride group can be seen that liver disorders are being promoted. On the other hand, when comparing the carbon tetrachloride group administered with carbon tetrachloride only and the carbon tetrachloride / GMT group administered with both carbon tetrachloride and GMT, the GOT and GPT levels were higher than the carbon tetrachloride / GMT group. It confirmed that it was reduced.

(5) 사염화탄소 투여와 LPO(5) carbon tetrachloride administration and LPO

또한, 표1 및 도2로부터, LPO량을 비교하면 사염화탄소를 투여하고 있지 않은 ① 대조군과, 사염화탄소를 투여한 ② 사염화탄소군을 비교하면, ② 사염화탄소군은 ① 대조군의 약 3.5배 큰 값을 나타내고 있다. 한편, 사염화탄소만을 투여하고 있는 ② 사염화탄소군과, 사염화탄소 및 GMT 모두를 투여한 ③ 사염화탄소/GMT군을 비교하면, ③ 사염화탄소/GMT군에서는, ② 사염화탄소군보다도 약 30% 정도 유의하게 저하되고 있는 것을 확인하였다.In addition, from Table 1 and FIG. 2, when comparing the amount of LPO, 1) control group which was not administered carbon tetrachloride and 2) carbon tetrachloride group, 2) carbon tetrachloride group showed approximately 3.5 times larger value than 1 control group. . On the other hand, when comparing the carbon tetrachloride group administered with carbon tetrachloride only and the carbon tetrachloride / GMT group administered with both carbon tetrachloride and GMT, ③ in the carbon tetrachloride / GMT group, the carbon tetrachloride was significantly reduced by about 30%. It was.

(6) 결론(6) Conclusion

GMT의 섭취는 에탄올의 연속섭취에 따른 혈청 GOT 및 GPT 활성이 상승하는 것을 억제하였다. 또한, GMT 섭취에 의해, 혈중 에탄올 및 아세트알데히드의 소실속도가 증가하였다. 그리고, GMT 섭취에 의해, 대조군보다 유의하게 높은 간장 ADH 및 ALDH 활성이 확인되었다. 또한, GMT 섭취에 의해, 사염화탄소 투여에 따른 혈청 GOT 및 GPT의 활성이 상승하는 것을 억제하며, LPO의 생성도 억제되고 있다. 이상으로부터, 미당ㆍ대두 발효추출물(GMT)을 섭취하면, 혈청 GOT 및 GPT 활성을 상승시키는 일이 없으며, 간장 알콜디히드로게나아제 및 알데히드디히드로게나아제 활성을 상승시키고 생체내에서의 알콜 대사를 향상시킬 뿐만 아니라, 동시에 알콜 및 사염화탄소에 의한 간장애를 경감할 수 있는 것다는 것을 알 수 있다.Ingestion of GMT inhibited the elevation of serum GOT and GPT activity following continuous intake of ethanol. In addition, GMT intake increased the rate of disappearance of blood ethanol and acetaldehyde. And GMT ingestion confirmed significantly higher hepatic ADH and ALDH activity than the control. In addition, the GMT intake suppresses the increase in the activity of serum GOT and GPT due to the administration of carbon tetrachloride, and the production of LPO is also suppressed. In view of the above, ingestion of sugar and soybean fermented extract (GMT) does not increase serum GOT and GPT activity, but increases liver alcohol dehydrogenase and aldehyde dehydrogenase activity and in vivo alcohol metabolism. In addition to improving, it can be seen that at the same time it is possible to alleviate liver disorders caused by alcohol and carbon tetrachloride.

또, 본 발명에 있어서는 상기 상세한 실시예에 나타낸 것에 한정되지 않고, 목적, 용도에 따라서 본 발명의 범위내에서 각종 변경한 실시예로 할 수 있다. 즉, 상기 미당ㆍ대두 발효추출물의 형태는 일반적으로 수용액 또는 원액 등의 액상이지만, 이것에 한정되지 않고 이 추출물을 흡액성 분말에 함침시킨 분말품, 조립된 조립품, 증량제 등의 기타 분말성분을 배합한 정제, 또는 마이크로캅셀 등으로 할 수 있다. 그리고, 이러한 수용액, 분말품 등을 소정의 용기에 충전하여 만든 상품형태, 또는 이들을 단독으로 사용하는 기타 제제(수용액인 것, 유성액인 것, 또는 분말이어도 상관없음)에 배합하여 사용하는 것에 대해서도 특히 한정되지 않으며, 예를 들어 포션형이어도 좋지만, 기타 형상의 용기에 충전하여도 좋고, 분말품을 스틱상 용기(자루)에 충전한 것이어도 좋다.In addition, in this invention, it is not limited to what was shown to the said detailed Example, According to the objective and a use, it can be set as the Example which variously changed within the range of this invention. That is, the form of the sugar-free or soybean fermented extract is generally a liquid such as an aqueous solution or a stock solution, but is not limited to this, and includes other powder components such as powdered products, granulated granules, and extenders impregnated into the liquid-absorbent powder. One tablet or microcapsule can be used. In addition, in the form of a product made by filling a predetermined container with such an aqueous solution or powdered product, or other formulations using these alone (which may be aqueous solutions, oily solutions, or powders), Although it does not specifically limit, For example, although it may be a potion type, you may fill in the container of other shape, and may fill in the stick-shaped container (sack) with powder.

또한, 이 추출물을 그대로 사용하여도 좋지만, 종래의 청량음료수, 드링크제, 유제품, 유제화 제품 등에 배합, 분산하여 사용하여도 좋다. 또, 이러한 분산은 유중수(油中水)형, 수중유(水中油)형이어도 상관없다. 그리고, 기타 영양성분(예를 들어, 각종 비타민류, 칼슘 이온성분, 철이온성분 등), 약효성분, 조미성분, 향기성분 등을 배합하여도 좋다. 이들 중, 균일하게 용해한 제품으로 할 수 있다는 측면에서, 수용성 성분이 특히 바람직하다.In addition, the extract may be used as it is, but may be blended and dispersed in a conventional soft drink, a drink, a dairy product, or an emulsified product. Moreover, such dispersion may be a water-in-oil type or an oil-in-water type. In addition, other nutrients (for example, various vitamins, calcium ions, iron ions, etc.), medicinal ingredients, seasonings, fragrances, etc. may be blended. Among them, a water-soluble component is particularly preferable in terms of being able to make the product dissolved uniformly.

본 발명의 알콜대사 향상제는 천연성분으로 이루어지기 때문에 생체내에서 안전할 뿐만 아니라, 우수한 알콜대사 향상작용을 나타낸다. 따라서, 알콜에 의한 간장애를 효과적으로 경감시킬 수 있는 것으로 사료된다.Alcohol metabolism enhancer of the present invention is not only safe in vivo because of the natural components, but also shows an excellent alcohol metabolism improving action. Therefore, it is considered that the liver disorder caused by alcohol can be effectively alleviated.

마찬가지로, 본 발명의 간장애 저감제도 천연성분으로 이루어지기 때문에 생체내에서 안전함과 동시에, 우수한 간장애 저감작용, 특히 알콜이나 사염화탄소 등의 할로겐화합물에 기인하는 간장애 저감작용을 나타낸다. 따라서, 간장애, 특히 알콜이나 사염화탄소 등의 할로겐화합물에 기인하는 간장애를 효과적으로 경감시킬 수 있으며, 일반적인 간장애의 예방ㆍ개선 이외에도, 치료현장에서의 약제성 간장애 예방ㆍ개선에도 바람직하게 사용할 수 있다.Similarly, since the liver disorder reducing agent of the present invention is made of natural ingredients, it is safe in vivo and exhibits excellent liver disorder reducing action, in particular, liver disease reducing action due to halogen compounds such as alcohol and carbon tetrachloride. Therefore, it is possible to effectively alleviate liver disorders, in particular, liver disorders caused by halogen compounds such as alcohol and carbon tetrachloride, and can be preferably used for the prevention and improvement of pharmaceutical liver disorders in the treatment field, in addition to the prevention and improvement of general liver disorders. have.

Claims (5)

미당류, 대두류 및 탄소원을 포함한 배지에 납두균 또는 고초균을 접종하고, 발효배양하여 얻어진 미당ㆍ대두 발효추출물을 함유하는 것을 특징으로 하는 알콜대사 향상제.An alcohol metabolism improving agent comprising a microsaccharide or soybean fermentation extract obtained by inoculating Bacillus aureus or Bacillus subtilis into a medium containing unsaccharides, soybeans, and a carbon source, followed by fermentation. 미당류, 대두류 및 탄소원을 포함한 배지에 납두균 또는 고초균을 접종하고, 발효배양하여 얻어진 미당ㆍ대두 발효추출물을 함유하는 것을 특징으로 하는 간장애 저감제.A hepatic impairment reducing agent, characterized in that the medium containing microsaccharides, soybeans, and carbon sources is inoculated with Bacillus subtilis or Bacillus subtilis, followed by fermentation culture. 제2항에 있어서, 상기 간장애는 알콜 유발성 간장애인 것을 특징으로 하는 간장애 저감제.The agent for reducing liver disorders according to claim 2, wherein the liver disorder is an alcohol-induced liver disorder. 제2항에 있어서, 상기 간장애는 할로겐계 화합물 유발성 간장애인 것을 특징으로 하는 간장애 저감제.The agent for reducing liver disorders according to claim 2, wherein the liver disorder is a halogen-based compound-induced liver disorder. 제4항에 있어서, 상기 할로겐계 화합물은 사염화탄소인 것을 특징으로 하는 간장애 저감제.5. The liver disorder reducing agent according to claim 4, wherein the halogen compound is carbon tetrachloride.
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