JP2009184998A - Liver function enhancer, tool for its production and use of them - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new liver function enhancer which enhances lowered liver function. <P>SOLUTION: A liver function enhancer is obtained by growing live Lactobacillus plantarum SN 13T in the presence of a fermentation raw material. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a liver function improving agent and a tool for producing the same, and use thereof, and more specifically, a liver function improving agent containing a specific plant lactic acid bacterium and / or a fermented product thereof and the production thereof. Tools and their use.

  It is known that liver dysfunction, which is a condition in which the liver function is not normal, is caused by hepatitis virus, excessive intake of alcohol, immunity / metabolism abnormalities, and the like. Liver dysfunction may progress from acute hepatitis to chronic hepatitis, further cirrhosis, and liver cancer, but mild liver dysfunction has few symptoms. In addition, a decrease in liver function essential for the homeostasis of organisms can be a cause of various diseases. Therefore, early detection and early improvement of liver dysfunction are required.

  Various drugs have been developed to improve the decrease in liver function. In recent years, various foods (for example, green fish, seafood, soy products, mushrooms, potatoes, etc.) are also expected to improve liver damage.

  Lactic acid bacteria have been used in many foods such as cheese, yoghurt, fermented butter, dairy products, fruit juices, vegetable juices, etc. since ancient times. It plays an important role. In recent years, as a physiological effect of lactic acid bacteria, an improvement effect of intestinal flora by inoculation with live lactic acid bacteria or an intestinal regulating action has been clarified, and lactic acid bacteria preparations have been developed as pharmaceuticals.

In Patent Document 1, when yogurt produced using a specific lactic acid bacterium is fed to rats for 2 months and then galactosamine is administered, the increase in GOT and GPT can be prevented by feeding yogurt in advance. It is disclosed. GOT and GPT, which are used as indicators of liver function, are enzymes originally involved in amino acid metabolism in cells. Such an enzyme that should originally be in the cells of the liver leaks out of the cells and continues to be present in the blood in a large amount, indicating that the destruction of the liver is continuing / progressing.
JP 2007-236227 A (published on September 20, 2007) JP 2006-42796 A (published February 16, 2006)

  Lactic acid bacteria include animal lactic acid bacteria collected from animals and plant lactic acid bacteria collected from plants. When producing fermented beverages such as fermented milk and fermented fruit juice, animal lactic acid bacteria are exclusively used because the growth of plant lactic acid bacteria is extremely slow or does not grow. Recently, fermented beverages using plant lactic acid bacteria have begun to admire, but since fermented beverages using plant lactic acid bacteria have hardly progressed in lactic acid fermentation, the flavor is far from fermented dairy products using general animal lactic acid bacteria.

  The present inventors have acquired new plant lactic acid bacteria and manufactured fermented beverages having new flavors and functions using these lactic acid bacteria (see Patent Document 2). The present inventors have also found that the strain used in Patent Document 1 does not have the effect of improving the decreased liver function.

  This invention is made | formed in view of said problem, The objective is to provide the new liver function improving agent which improves the reduced liver function.

  The present inventors have found that a specific plant lactic acid bacterium exhibits an effect of improving liver function while advancing research on plant lactic acid bacteria, and have completed the present invention. That is, the method for producing a liver function improving agent according to the present invention includes a mixing step of mixing a viable strain of Lactobacillus plantarum SN13T strain viable with a fermentation raw material, and in the presence of the fermentation raw material. And a growth step of growing the viable bacteria.

  In the production method according to the present invention, the fermentation raw material is preferably selected from the group consisting of milk, fruit juice and vegetable juice. Moreover, in the manufacturing method which concerns on this invention, it is preferable that the said mixing process further includes adding sake lees, shochu distillation residue, or these extracts.

  The liver function improving agent manufactured by the above-described manufacturing method is also within the scope of the present invention, and the liver function improving agent according to the present invention is fermented by a living bacterium of Lactobacillus plantarum SN13T strain having a lactic acid acidity of 0. An amount corresponding to 50 to 200 g of fermented milk within the range of 6 to 1.5% may be prescribed for daily intake for at least two weeks.

  The functional food according to the present invention is characterized in that it contains the liver function improving agent, and the liver function improving agent itself may be a functional food.

  Moreover, the usage method for manufacturing the functional food which improves the liver function based on this invention uses the fermented material fermented with the living microbe of Lactobacillus plantarum SN13T strain | stump | stock, or this live microbe.

  The method for evaluating a liver function improving agent according to the present invention includes a step of examining whether or not a Lactobacillus plantarum SN13T strain is contained in a sample to be evaluated.

  The composition according to the present invention is characterized in that it contains viable bacteria of Lactobacillus plantarum SN13T strain in order to produce a liver function improving agent. The composition which concerns on this invention may further contain the fermentation raw material fermented with the said living microbe. In this case, the fermentation raw material is preferably selected from the group consisting of milk, fruit juice and vegetable juice. In addition, the composition according to the present invention may further contain sake lees or shochu distillation residues or extracts thereof.

  If this invention is used, the liver function improving agent which can implement | achieve a liver function improvement can be manufactured. Therefore, if this invention is used, the functional food which can implement | achieve the new function of liver function improvement can be provided. Moreover, if this invention is used, evaluation of a liver function improving agent will be attained.

[1] Composition for producing a liver function improving agent The present invention provides a composition containing viable bacteria of Lactobacillus plantarum SN13T strain in a viable manner. If the composition which concerns on this invention is used, a liver function improving agent can be manufactured.

  The Lactobacillus plantarum SN13T strain is a strain isolated by the present inventors and has been deposited as an accession number NITE P-7 with the Patent Microorganism Depositary of the National Institute of Technology and Evaluation, the following bacteriological It has properties: isolate from sausage called Nam from Thailand, gram-positive lactobacilli, homo-type fermentation, catalase negative, no spore-forming ability, cultivatable even under aerobic conditions, taxonomic position is Lactobacillus plantarum.

  In addition to the Lactobacillus plantarum SN13T strain, the present inventors, as well as the Lactobacillus plantarum SN13T strain, the Lactobacillus plantarum SN35N strain, the Lactobacillus plantarum SN35M strain, the Lactococcus lactis subspecies lactis SN26N strain, the Enterococcus spice SN21I strain, And Enterococcus munti SN29N strain have been isolated so far. Many other plant lactic acid bacteria are known (see, for example, Patent Documents 1 and 2). However, it was not known at all that Lactobacillus plantarum SN13T strain had an excellent effect of improving liver function among such a wide variety of plant lactic acid bacteria. Patent Document 1 discloses that galactosamine-induced hepatic dysfunction (an increase in GOT and GPT) can be prevented by feeding a rat with yogurt produced using a specific lactic acid bacterium for 2 months in advance. However, the lactic acid bacterium Streptococcus thermophilus, which has been demonstrated to have such a function, did not show an effect of improving liver function.

  The composition according to the present invention may further contain a fermentation raw material that is fermented by the Lactobacillus plantarum SN13T strain. In addition, the composition according to the present invention may further contain sake lees or shochu distillation residues or extracts thereof.

  As used herein, the term “composition” may be an embodiment in which the components are contained in a single composition or an embodiment in which the components are separately provided in a single kit. That is, the composition according to the present invention may further contain a fermentation raw material, but the composition containing the viable bacteria of Lactobacillus plantarum SN13T strain viably and a fermentation raw material are separately provided. Form may be sufficient. Further, the composition according to the present invention may further contain a sake lees or shochu distillation residue or an extract thereof. However, the composition according to the present invention and the sake lees or shochu distillation residue or an extract thereof are separately provided. It may be in the form of a kit.

  The fermentation raw material used in the present invention is preferably selected from the group consisting of milk, fruit juice and vegetable juice. Examples of the milk include animal milk (for example, cow's milk, goat milk, and sheep milk), and milk is particularly preferable. The milk may be either non-sterilized milk or pasteurized milk, and concentrated milk or condensed milk prepared from these milks, skim milk, partially skimmed milk or powdered milk obtained by drying these powders, etc. There may be. Examples of fruit juice include, but are not limited to, peach, apple, and strawberry juice. Examples of vegetable juice include, but are not limited to, carrot, tomato, cabbage and other juices. Fruit juice and vegetable juice are obtained by grinding fruit or vegetable with a mixer or the like, and further squeezing if necessary. Such fruit juices and vegetable juices may be concentrated as appropriate, and the concentrated solution may be used as it is or after being diluted to an appropriate concentration with distilled water or the like.

  The milk, fruit juice, and vegetable juice described above may be used alone or in combination according to the purpose.

  In the present specification, the term “containing viable bacteria viable” is not particularly limited as long as the target strain is maintained in the composition without dying. That is, in the composition, the target viable bacteria may be growing or may be dormant. In one embodiment, the composition according to the present invention preferably further contains a fermentation raw material fermented by Lactobacillus plantarum SN13T strain, and further contains sake lees or shochu distillation residues or extracts thereof. Is preferred. In such a form, since the enzymatic activity of the living bacteria of Lactobacillus plantarum SN13T strain can be kept high, the living bacteria can be contained viable in the composition. In another embodiment, the composition according to the present invention comprises live bacteria of Lactobacillus plantarum strain SN13T along with suitable excipients. Excipients that do not affect the survival of lactic acid bacteria are well known in the art and include, for example, starch, dry yeast, lactose, sucrose, and the like for processing the composition into tablets (eg, corn Peptide, maltose, etc.).

  Although the composition for producing the liver function improving agent according to the present invention is intended to be a so-called “fermented species”, live bacteria of Lactobacillus plantarum SN13T strain (and its fermented product) are used as the liver function improving agent. The aspect of containing to such an extent that it can function as may be sufficient. This case is described in detail below as a “liver function improving agent”. In addition, the composition according to the present invention can be provided in any form such as a solution form or a solid form (eg, tablet, capsule, etc.).

[2] Liver function improving agent and production method thereof The present invention provides a liver function improving agent produced using plant lactic acid bacteria. The liver function improving agent according to the present invention may be a pharmaceutical composition or an edible composition. In one embodiment, the liver function improving agent according to the present invention is characterized by being manufactured using a composition containing viable bacteria of Lactobacillus plantarum SN13T strain viably. That is, the method for producing a liver function improving agent according to the present invention comprises a mixing step of mixing a viable strain of Lactobacillus plantarum SN13T strain viable with a fermentation raw material, and in the presence of the fermentation raw material. And a growth step of growing the viable bacteria, and is characterized by containing “Lactobacillus plantarum SN13T strain and / or its fermented product” obtained through these steps.

  The fermentation raw material used in the mixing step of the present invention is not particularly limited as long as it is described above. Moreover, it is preferable that the mixing process of this invention further includes adding sake lees, shochu distillation residue, or these extracts. The details of the sake lees or shochu distillation residue or their extracts are described in Patent Document 2 incorporated by reference in the present specification, and can be easily understood by those skilled in the art.

  The growth process of the present invention may be a fermentation process in which the fermentation raw material is fermented with the above-mentioned live bacteria, and the fermentation process preferably ferments the fermentation raw material until the acidity falls within the range of 0.6 to 1.5%. . Fermentation should just be performed using a well-known method in the said field | area using milk, fruit juice, or vegetable juice as a fermentation raw material. The same applies to the case where sake lees or shochu distillation residues or their extracts are added.

  In addition, although milk was used as a fermentation raw material in the examples, when fruit juice or vegetable juice is used, fruit juice or vegetable juice or a solution obtained by adding other raw materials to these is heat sterilized at 65 to 130 ° C. for 1 second to 30 minutes. And then cooled to 30 to 45 ° C., and subsequently inoculated with 0.1 to 6% by weight of the plant lactic acid bacteria in this solution, then fermented at a temperature of 30 to 45 ° C. for 12 to 72 hours, and cooled after completion of the fermentation What is necessary is just to use a thing as fermented material (fermented fruit juice or fermented vegetable juice). These fermented fruit juice or fermented vegetable juice may be used as a beverage as it is, or may be further diluted or sterilized to obtain a fermented fruit juice drink or fermented vegetable juice drink.

  In addition, when obtaining fermented material, the raw material normally used for manufacture of fermented drinks, such as gelatin, agar, saccharides, a fragrance | flavor, and a pulp, can also be added other than a fermentation raw material. For example, sugars such as sucrose, glucose, fructose, palatinose, trehalose, sugar alcohols such as sorbitol, xylitol, erythritol, reduced starch syrup, high sweetness sweeteners such as aspartame, acesulfame potassium, sucrose fatty acid ester, glycerin fatty acid ester, Emulsifiers such as lecithin, thickeners such as carrageenan, xanthan gum and guar gum, acidulants such as citric acid, lactic acid and malic acid, juices such as lemon juice and orange juice, vitamins, calcium, iron, manganese and zinc Furthermore, it is possible to add herbal medicines such as licorice, katsushi, ginger, or food additives such as herbs, sodium glutamate, gardenia pigments, silicone, and phosphates.

[2-1] Pharmaceutical Composition The present invention provides a pharmaceutical composition for improving liver function, comprising “Lactobacillus plantarum SN13T strain and / or its fermented product”. In one embodiment, the pharmaceutical composition according to the present invention may consist of Lactobacillus plantarum SN13T strain and / or its fermentation product. As used herein, the term “pharmaceutical composition” intends a composition having a form other than the composition provided as the edible composition described below.

  The pharmaceutical composition according to the present invention can be produced by a known method in the pharmaceutical field. The content of “Lactobacillus plantarum SN13T strain and / or its fermented product” in the pharmaceutical composition according to the present invention takes into consideration the administration form, administration method, and the like, and using this pharmaceutical composition, “Lactobacillus plantarum SN13T strain and The “/ or fermented product thereof” is not particularly limited as long as it can be administered in an appropriate amount. In one embodiment, the pharmaceutical composition according to the present invention is an amount corresponding to 50 to 200 g of fermented milk fermented by live bacteria of Lactobacillus plantarum SN13T strain and having an acidity in the range of 0.6 to 1.5%. Is taken as a daily intake for at least 2 consecutive weeks.

  The pharmaceutical composition according to the present invention is preferably administered orally, and can be prepared in the form of tablets, capsules and the like that are preferable for oral administration. In the case of an oral administration mode (that is, oral preparation), for example, starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, inorganic salt and the like are used as a pharmaceutical carrier. Moreover, when preparing an oral preparation, you may mix | blend a binder, a disintegrating agent, surfactant, a lubricant, a fluidity promoter, a corrigent, a coloring agent, a fragrance | flavor, etc. further. Auxiliary substances such as stabilizers, antioxidants and the like may also be present in the pharmaceutical composition according to the invention.

  The pharmaceutical composition according to the present invention can be orally administered as it is, or can be added to any food or drink and taken daily. Administration and ingestion may be performed once or divided into several times within a day within a desired dose range.

[2-2] Edible composition The present invention provides an edible composition for improving liver function (ie, food, beverage, etc.) containing “Lactobacillus plantarum SN13T strain and / or its fermented product”. provide. In one embodiment, the edible composition according to the present invention may consist of Lactobacillus plantarum SN13T strain and / or its fermentation product.

  The method for producing the edible composition according to the present invention is not particularly limited, and examples thereof include cooking, processing, and production by a generally used method for producing foods or beverages. The produced foods or beverages include “Lactobacillus plantarum”. The SN13T strain and / or the fermented product thereof may be contained. In one embodiment, the edible composition according to the present invention is fermented by live bacteria of Lactobacillus plantarum strain SN13T, the amount corresponding to 50 to 200 g of fermented milk having an acidity within the range of 0.6 to 1.5%. Is taken as a daily intake for at least 2 consecutive weeks.

  Examples of the edible composition according to the present invention include dairy products (eg, yogurt), health foods (eg, capsules, tablets, powders), beverages (eg, milk beverages, vegetable beverages, etc.), and drinks. However, it is not limited to these. The food or beverage according to the present invention is extremely useful as a health food (functional food) for improving liver function.

[3] Use of Lactobacillus plantarum SN13T strain As described above, it was newly found that the Lactobacillus plantarum SN13T strain exhibits an effect of improving liver function. Based on such knowledge, in order to produce a functional food that improves liver function, a method using live bacteria of Lactobacillus plantarum SN13T strain or a fermented product fermented with the live bacteria, or Lactobacillus plantarum SN13T strain It has been read that the present invention also provides a method for evaluating whether a sample can function as a liver function improving agent based on testing whether or not it is contained. Those skilled in the art will readily understand. In addition, those skilled in the art can easily understand the steps defining these methods based on the description of the present specification.

  The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope shown in the claims, and embodiments obtained by appropriately combining technical means disclosed in different embodiments. Is also included in the technical scope of the present invention. Moreover, all the academic literatures and patent literatures described in this specification are incorporated herein by reference.

  The concentration of the non-fat milk solid content of the milk was adjusted to 8.0% or more. This solution was sterilized by heating at 65 to 130 ° C. for 1 second to 30 minutes and cooled to 30 to 45 ° C. This solution was inoculated with 0.1 to 6% by weight of lactic acid bacteria. After inoculation, fermentation was carried out at 30 to 45 ° C. until the amount of lactic acid bacteria reached 10 million cells / ml or more (3 to 72 hours). Samples A and B were cooled to 10 ° C. or less after the end of fermentation. The lactic acid bacteria used for the preparation of Sample A were plant lactic acid bacteria (Lactobacillus plantarum SN13T strain), and the lactic acid bacteria used for the preparation of Sample B were animal lactic acid bacteria (Lactococcus lactis (86.1%), Streptococcus thermophilus (13. 8%), Lactobacillus bugaricus (0.1%)).

  A double-blind randomized controlled trial was performed. A subject who took 100 g of each sample every day for 6 weeks was subjected to blood biochemical tests at the start of intake and every 2 weeks after the start of intake. In addition, since the main examination item of this test was evaluation of the intestinal regulating action, the subjects were divided into three layers according to the number of defecations per week, and stratified random assignment was performed on sample A and sample B.

  The transition of the average values of GOT, GPT and γ-GTP in the sample A intake group and the sample B intake group, and the transition of the change rate when the pre-test food intake is 1, are shown in FIGS. As shown in FIGS. 1 to 3, among the evaluated blood biochemical parameters, GOT, GPT, and γ-GTP, which are indicators of liver function, show a tendency to decrease in three parameter values even by continuous ingestion of sample B. However, GOT, GPT, and γ-GTP were all significantly reduced by continuous intake of Sample A, and the decrease was particularly remarkable in γ-GTP.

  Thus, it was found that Sample A has an ability to improve liver function. In addition, since the subject assignment was performed in consideration of the intestinal regulating action, the average of the numerical values of the liver function before the intake of the test meal varied between the groups. However, even when analyzed based on the rate of change from before the sample intake, the sample A intake group clearly showed a decrease (improvement) in the test value. In addition, the increase in the measured value at 6 weeks after ingestion is thought to be due to the increased chances of drinking at the end of the year.

  According to the present invention, a new technique for improving liver function is provided. As described above, the present invention greatly contributes to industrial development in fields related to medicines and foods.

It is a figure which shows the fluctuation | variation of the blood GOT value in the test subject who ingested the liver function improving agent (sample A) and control (sample B) which concern on this invention. It is a figure which shows the fluctuation | variation of the blood GPT value in the test subject who ingested the liver function improving agent (sample A) and control (sample B) which concern on this invention. It is a figure which shows the fluctuation | variation of the blood (gamma) -GTP value in the test subject who ingested the liver function improving agent (sample A) and control (sample B) which concern on this invention.

Claims (12)

A method for producing a liver function improving agent,
A mixing step of mixing a viable composition of Lactobacillus plantarum SN13T strain (accession number: NITE P-7) with a fermentation raw material; and proliferating the viable microorganism in the presence of the fermentation raw material The manufacturing method characterized by including the proliferation process to be made.   The production method according to claim 1, wherein the fermentation raw material is selected from the group consisting of milk, fruit juice and vegetable juice.   The manufacturing method according to claim 2, wherein the mixing step further includes adding sake lees or shochu distillation residue or extracts thereof.   The liver function improving agent manufactured by the manufacturing method of Claims 1-3.   Lactobacillus plantarum SN13T strain (Accession number: NITE P-7) fermented by viable bacteria, the amount corresponding to 50 to 200 g of fermented milk having an acidity within the range of 0.6 to 1.5% As a liver function improving agent, characterized in that it is prescribed for continuous intake for at least 2 weeks.   A functional food comprising the liver function improving agent according to claim 4 or 5.   A method of using a living bacterium of Lactobacillus plantarum SN13T strain (Accession No .: NITE P-7) or a fermented product fermented by the living bacterium to produce a functional food that improves liver function. A method for evaluating a liver function improving agent,
A method for evaluating whether or not a Lactobacillus plantarum SN13T strain (Accession Number: NITE P-7) is contained in a sample to be evaluated.   A composition for producing a liver function improving agent characterized by containing a viable bacterium of Lactobacillus plantarum SN13T strain (Accession No .: NITE P-7) in a viable manner.   The composition according to claim 9, further comprising a fermentation raw material that is fermented by the live bacteria.   11. The composition according to claim 10, wherein the fermentation raw material is selected from the group consisting of milk, fruit juice and vegetable juice.   The composition according to any one of claims 9 to 11, further comprising a sake lees or shochu distillation residue or an extract thereof.

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