Preventative and / or inhibiting agent for intestinal hyperpermeability, composition for preventing and / or inhibiting intestinal hyperpermeability, agent for preventing liver function deterioration and / or improving liver function, and composition for preventing liver function deterioration and / or improving liver function

Abstract

This preventative and / or inhibiting agent for intestinal hyperpermeability is used for preventing and / or inhibiting intestinal hyperpermeability, and contains cells of Lactobacillus plantarum 22A-3 strain (FERM BP-21411).

Description

Agent for preventing and / or suppressing increased intestinal permeability, composition for preventing and / or suppressing increased intestinal permeability, agent for preventing liver dysfunction and / or improving liver function, and composition for preventing liver dysfunction and / or improving liver function

[0001] The present invention relates to an agent for preventing and / or suppressing increased intestinal permeability, a composition for preventing and / or suppressing increased intestinal permeability, an agent for preventing and / or improving liver function, and a composition for preventing and / or improving liver function.

[0002] The intestinal tract has the function of absorbing nutrients and a barrier function that prevents intestinal bacteria and other microorganisms from entering the body (bloodstream). The barrier function works by restricting the permeation of substances through the gaps between intestinal epithelial cells using adhesive structures called tight junctions that tightly connect adjacent cells.

[0003] When the barrier function of the intestinal tract declines, i.e., when intestinal permeability increases, intestinal bacteria, harmful substances, undigested food, and other substances that normally do not pass through the intestinal tract leak into the body. When these substances leak into the body, they enter the bloodstream and cause inflammation in various parts of the body, which is said to be involved in autoimmune diseases and other conditions. The condition in which such substances leak into the body and cause disease is called leaky gut (leaky gut syndrome).

[0004] In addition, an example of a condition known to be associated with increased intestinal permeability is decreased liver function. Increased intestinal permeability allows harmful substances that pass through the intestinal tract and enter the bloodstream to be transported to the liver, causing inflammation. This impairs the liver's normal functions, leading to decreased liver function. Therefore, it is believed that preventing and / or suppressing increased intestinal permeability can prevent decreased liver function and improve liver function.

[0005] A composition for inhibiting increased intestinal permeability, which is characterized by containing at least one member of the group consisting of galactomannan, indigestible dextrin, and salt of alginic acid, has been proposed (see, for example, Patent Document 1).

[0006] JP 2016-193895 A

[0007] As described above, materials having an inhibitory effect on increased intestinal permeability have been proposed to date. However, there remains a strong demand for new materials that can prevent and / or inhibit increased intestinal permeability, are highly safe, are useful for preventing and / or inhibiting increased intestinal permeability and for preventing liver dysfunction and / or improving liver function, and can therefore be widely used as components of foods and beverages, pharmaceuticals, quasi-drugs, research reagents, etc., and there is currently a demand for their prompt development.

[0008] The present invention aims to solve the above-mentioned conventional problems and to achieve the following objects: That is, the present invention aims to provide a preventive and / or suppressive agent for and / or composition for preventing and / or suppressing increased intestinal permeability that can prevent and / or suppress increased intestinal permeability and are highly safe, as well as a preventive and / or improving agent for and / or composition for preventing decreased liver function and / or improving liver function that can prevent and / or improve liver function and are highly safe.

[0009] As a result of intensive research conducted by the present inventors to solve the above problems, they have found that the highly safe Lactobacillus plantarum 22A-3 strain (FERM BP-21411) can prevent and / or suppress increased intestinal permeability and prevent and / or improve liver function, and is a useful material for preventing and / or suppressing increased intestinal permeability and preventing and / or improving liver function.

[0010] The present invention is based on the above-mentioned findings of the present inventors, and provides the following means for solving the above problems. Namely, <1> An agent for preventing and / or suppressing increased intestinal permeability, which is used for preventing and / or suppressing increased intestinal permeability and contains cells of Lactobacillus plantarum 22A-3 strain (FERM BP-21411). <2> A composition for preventing and / or suppressing increased intestinal permeability, which contains the agent for preventing and / or suppressing increased intestinal permeability described in <1>. <3> An agent for preventing liver function decline and / or improving liver function, which is used for preventing liver function decline and / or improving liver function, and which comprises cells of Lactobacillus plantarum 22A-3 strain (FERM BP-21411). <4> A composition for preventing liver function decline and / or improving liver function, which comprises the agent for preventing liver function decline and / or improving liver function described in <3>.

[0011] According to the present invention, the above-mentioned problems of the prior art can be solved, the above-mentioned object can be achieved, and a preventive and / or suppressive agent for preventing and / or suppressing increased intestinal permeability and a composition for preventing and / or suppressing increased intestinal permeability that are highly safe can be provided, as well as a preventive and / or improving agent for preventing and / or improving liver function and a composition for preventing and / or improving liver function that are highly safe and can prevent and / or improve liver function.

[0012] Fig. 1 shows the results of Test Example 1. Fig. 2 is a graph showing the change in the measured value of alanine aminotransferase in Test Example 2. Fig. 3 is a graph showing the change in the measured value of aspartate aminotransferase in Test Example 2. Fig. 4 is a graph showing the change in the measured value of γ-glutamyltranspeptidase in Test Example 2.

[0013] (Agent for preventing and / or suppressing increased intestinal permeability, and agent for preventing liver dysfunction and / or improving liver function) The agent for preventing and / or suppressing increased intestinal permeability of the present invention is used to prevent and / or suppress increased intestinal permeability, and contains at least Lactobacillus plantarum 22A-3 strain (FERM BP-21411) cells, and may further contain other components as necessary.

[0014] As used herein, "preventing increased intestinal permeability" refers to maintaining a normal state of intestinal permeability or bringing it closer to the normal state, and "suppressing increased intestinal permeability" refers to reducing intestinal permeability and bringing increased intestinal permeability back to the normal state or bringing it closer to the normal state.

[0015] The method for confirming the state of intestinal permeability is not particularly limited and can be appropriately selected depending on the purpose. For example, the concentration of zonulin in the blood can be used as an indicator. Zonulin is a protein that causes the breakdown of tight junctions between intestinal epithelial cells and the subsequent increase in intestinal permeability. Therefore, an increase in the concentration of zonulin in the blood is associated with an increase in intestinal permeability, and the concentration of zonulin in the blood is known to be an indicator of intestinal permeability. Specifically, an increase in the concentration of zonulin in the blood can be determined to indicate an increased state of intestinal permeability, while a decrease in the concentration of zonulin in the blood can be determined to indicate an inhibited state of intestinal permeability.

[0016] The agent for preventing liver function decline and / or improving liver function of the present invention is used for preventing liver function decline and / or improving liver function, and contains at least Lactobacillus plantarum 22A-3 strain (FERM BP-21411) cells, and may further contain other components as necessary.

[0017] As used herein, "preventing liver function decline" refers to maintaining liver function at a normal state or bringing it closer to a normal state. Furthermore, as used herein, "improving liver function" refers to restoring liver function that has declined to a normal state or bringing it closer to a normal state. The agent for preventing liver function decline and / or improving liver function of the present invention can be suitably used to prevent liver function decline caused by increased intestinal permeability and to improve liver function that has declined due to increased intestinal permeability.

[0018] The method for confirming the state of liver function is not particularly limited, and known indicators can be appropriately selected depending on the purpose. For example, the following items listed as liver function test items in blood tests can be used as indicators: AST, ALT, γ-GTP, total protein, albumin, albumin / globulin ratio, triglycerides, total cholesterol, cholinesterase, lactate dehydrogenase, ammonia, prothrombin time, activated partial thromboplastin time, total pyruvilin, alkaline phosphatase, LAP, serum colloid reaction (ZTT / TTT), γ-globulin (immunoglobulin), platelet count, etc.

[0019] <Lactobacillus plantarum 22A-3 strain (FERM BP-21411) bacterial cells> It has not been known before that the Lactobacillus plantarum 22A-3 strain (hereinafter sometimes referred to as "LP22A-3 strain") bacterial cells can prevent and / or suppress increased intestinal permeability, and can prevent a decline in liver function and / or improve liver function, and this is a new finding made by the present inventors.

[0020] The LP22A-3 strain was isolated and identified by the present applicant from pickles, and has tannase activity, no gallic acid decarboxylase activity, and the ability to assimilate inulin.

[0021] The LP22A-3 strain was deposited domestically on October 22, 2007, and then, on May 31, 2023, a request for transfer to international deposit under the Budapest Treaty was made, and the strain was deposited as FERM BP-21411 at the National Institute of Technology and Evaluation, Patent Organism Depositary Center (Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture).

[0022] The method for culturing the LP22A-3 strain is not particularly limited, and any known method for culturing lactic acid bacteria can be appropriately selected.

[0023] The medium used for culturing the LP22A-3 strain is not particularly limited, and a medium commonly used for culturing lactic acid bacteria or a modified medium thereof can be used. Examples of medium components to be incorporated into the medium include components suitable for the growth of lactic acid bacteria, such as carbon sources such as glucose; nitrogen sources such as yeast extract, meat extract, casein, and protein hydrolysates thereof; inorganic salts such as sodium chloride, sodium phosphate, potassium phosphate, ammonium citrate, and magnesium sulfate; and vitamins such as thiamine and inositol.

[0024] The culture conditions for culturing the LP22A-3 strain, such as medium pH, culture temperature, culture time, and culture method, are not particularly limited and can be appropriately selected from known conditions. For example, the culture temperature is preferably 25°C to 45°C, and more preferably 30°C to 37°C. The culture time is preferably 4 hours to 74 hours, and more preferably 18 hours to 48 hours. Examples of the culture method include standing, stirring, shaking, and aeration.

[0025] The LP22A-3 strain may be used as the cells in a culture (sometimes referred to as a "fermented product") containing the cells, or may be separated from the culture and used as the cells.

[0026] The method for separating the cells of the LP22A-3 strain from the culture is not particularly limited, and any known method can be appropriately selected, such as centrifugation or filtration.

[0027] The LP22A-3 strain cells or a culture containing the cells may be concentrated or dried, if necessary.

[0028] The LP22A-3 strain may be a live bacterium or a killed bacterium.

[0029] The LP22A-3 strain cells have an excellent effect of reducing intestinal permeability and an excellent effect of preventing and / or improving liver function decline, and therefore can be used as an active ingredient of an agent for preventing and / or suppressing increased intestinal permeability, or an agent for preventing liver function decline and / or improving liver function.

[0030] The agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing decreased liver function and / or improving liver function, may consist solely of the LP22A-3 strain cells, or may be a formulation of the LP22A-3 strain cells.

[0031] The LP22A-3 strain cells can be formulated into any dosage form, such as powder, granules, tablets, or liquid, using a pharmaceutically acceptable carrier such as dextrin or cyclodextrin, or any other auxiliary agent, according to a conventional method. In this case, examples of the auxiliary agent that can be used include excipients, binders, disintegrants, lubricants, stabilizers, and flavoring / flavoring agents.

[0032] The agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing liver function decline and / or improving liver function, can be incorporated into other compositions (e.g., a composition for preventing and / or suppressing increased intestinal permeability, a composition for preventing liver function decline and / or improving liver function, etc., as described below), and can also be used as oral administration agents such as tablets, powders, capsules, granules, extracts, syrups, etc.; parenteral administration agents such as injections, drips, suppositories, etc.; ointments, eye drops, external liquids, patches, etc.

[0033] The content of the LP22A-3 strain cells in the formulated agent for preventing and / or suppressing increased intestinal permeability, or agent for preventing liver dysfunction and / or improving liver function, is not particularly limited and can be appropriately selected depending on the purpose. For example, the number of the LP22A-3 strain cells is 1.0 × 10 ７ pieces / g~1.0×10 １３ pieces / g, etc.

[0034] <Other Components> The other components are not particularly limited as long as they do not impair the effects of the present invention, and can be appropriately selected depending on the form of use of the agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing liver function decline and / or improving liver function, and examples thereof include the above-mentioned components that can be used when formulating the drug. The other components may be used alone or in combination of two or more.

[0035] The content of the other ingredients in the agent for preventing and / or suppressing increased intestinal permeability or the agent for preventing liver function decline and / or improving liver function is not particularly limited and can be selected appropriately depending on the purpose.

[0036] The method of use of the agent for preventing and / or suppressing increased intestinal permeability or the agent for preventing decreased liver function and / or improving liver function is not particularly limited and can be appropriately selected depending on the purpose. Examples include oral administration, parenteral administration, and topical administration, with oral administration being preferred.

[0037] The dosage form of the agent for preventing and / or suppressing increased intestinal permeability or the agent for preventing liver function decline and / or improving liver function is not particularly limited, and any known dosage form can be appropriately selected depending on the purpose. The method for producing the agent for preventing and / or suppressing increased intestinal permeability or the agent for preventing liver function decline and / or improving liver function is not particularly limited, and any known method can be appropriately selected depending on the dosage form.

[0038] The dosage, administration site, administration period, administration interval (hereinafter sometimes referred to as "usage amount, administration site, use period, administration interval") of the agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing liver function decline and / or improving liver function, is not particularly limited and can be selected appropriately depending on the purpose.

[0039] The amount of the agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing liver function decline and / or improving liver function (hereinafter, may be referred to as "intake amount") to be used is not particularly limited and can be appropriately selected depending on the purpose. For example, the amount of the LP22A-3 strain to be taken per day may be 1.0 × 10 ７ pieces ~ 1.0×10 １３The amount used as the agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing liver function decline and / or liver function improving agent is not particularly limited, and can be appropriately selected depending on the amount of bacterial cells of the LP22A-3 strain contained in the agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing liver function decline and / or liver function improving agent, etc.

[0040] The agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing liver dysfunction and / or improving liver function, is highly safe and can be used daily, and therefore can be used continuously, for example, once or more times a day. The period of continuous use is, for example, preferably 4 weeks or more, more preferably 6 weeks or more, and particularly preferably 8 weeks or more.

[0041] The agent for preventing and / or suppressing increased intestinal permeability can prevent and / or suppress increased intestinal permeability through the excellent intestinal permeability-reducing effect of the LP22A-3 strain cells, and can be used for all applications in which it is meaningful to prevent and / or suppress increased intestinal permeability.

[0042] The agent for preventing liver function decline and / or improving liver function can prevent liver function decline and / or improve liver function through the excellent intestinal permeability reducing effect of the LP22A-3 strain cells, and can be used for all applications in which preventing liver function decline and / or improving liver function are significant.

[0043] The agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing liver function decline and / or improving liver function, can be used in a wide range of applications, such as pharmaceuticals, quasi-drugs, oral compositions, cosmetics, and research reagents. For example, the agent for preventing and / or suppressing increased intestinal permeability can be suitably used as a component of a composition for preventing and / or suppressing increased intestinal permeability, as described below, and the agent for preventing liver function decline and / or improving liver function can be suitably used as a component of a composition for preventing liver function decline and / or improving liver function, as described below. In this case, the LP22A-3 strain bacterial cells may be blended directly, or a formulation of the LP22A-3 strain bacterial cells may be blended.

[0044] The agent for preventing and / or suppressing increased intestinal permeability may, if necessary, be formulated with other ingredients having an effect of preventing and / or suppressing increased intestinal permeability together with the LP22A-3 strain cells as active ingredients.Furthermore, the agent for preventing and / or improving liver function may, if necessary, be formulated with other ingredients having an effect of preventing liver function decline and / or improving liver function together with the LP22A-3 strain cells as active ingredients.

[0045] The agent for preventing and / or suppressing increased intestinal permeability, or the agent for preventing decreased liver function and / or improving liver function, is preferably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as its functional effects are achieved.

[0046] (Composition for preventing and / or suppressing increased intestinal permeability, composition for preventing liver dysfunction and / or improving liver function) The composition for preventing and / or suppressing increased intestinal permeability of the present invention contains at least the agent for preventing and / or suppressing increased intestinal permeability of the present invention, and further contains other ingredients as necessary.

[0047] The composition for preventing liver function decline and / or improving liver function of the present invention contains at least the agent for preventing liver function decline and / or improving liver function of the present invention, and further contains other ingredients as necessary.

[0048] <Agent for preventing and / or suppressing increased intestinal permeability, agent for preventing liver dysfunction and / or improving liver function> The agent for preventing and / or suppressing increased intestinal permeability is the agent for preventing and / or suppressing increased intestinal permeability of the present invention described above. The content of the agent for preventing and / or suppressing increased intestinal permeability in the composition for preventing and / or suppressing increased intestinal permeability is not particularly limited, and can be appropriately adjusted depending on the form of the composition for preventing and / or suppressing increased intestinal permeability. For example, when the intake amount of the LP22A-3 strain is 1.0 x 10 per day in terms of bacterial count, ７ pieces ~ 1.0×10 １３ The composition for preventing and / or suppressing increased intestinal permeability may consist solely of the agent for preventing and / or suppressing increased intestinal permeability.

[0049] The agent for preventing liver function decline and / or improving liver function is the agent for preventing liver function decline and / or improving liver function of the present invention described above. The content of the agent for preventing liver function decline and / or improving liver function in the composition for preventing liver function decline and / or improving liver function is not particularly limited, and can be appropriately adjusted depending on the form of the composition for preventing liver function decline and / or improving liver function. For example, when the intake amount of the LP22A-3 strain is 1.0 × 10 per day in terms of bacterial count, ７ pieces ~ 1.0×10 １３ The composition for preventing liver function decline and / or improving liver function may consist solely of the agent for preventing liver function decline and / or improving liver function.

[0050] <Other Components> The other components in the composition for preventing and / or suppressing increased intestinal permeability or the composition for preventing liver function decline and / or improving liver function are not particularly limited and can be appropriately selected depending on the form of use of the composition for preventing and / or suppressing increased intestinal permeability or the composition for preventing liver function decline and / or improving liver function, and examples thereof include the same as the other components described in the above section "Agent for preventing and / or suppressing increased intestinal permeability, agent for preventing liver function decline and / or improving liver function." These may be used alone or in combination of two or more.

[0051] The content of the other ingredients in the composition for preventing and / or suppressing increased intestinal permeability or the composition for preventing liver function decline and / or improving liver function is not particularly limited and can be selected appropriately depending on the purpose.

[0052] <Aspects> The aspect of the composition for preventing and / or suppressing increased intestinal permeability or the composition for preventing liver function decline and / or improving liver function is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include pharmaceuticals, quasi-drugs, foods and beverages, etc.

[0053] The composition of the present invention for preventing and / or suppressing increased intestinal permeability, or for preventing liver dysfunction and / or improving liver function, is highly safe and can be used on a daily basis, and due to the action of the LP22A-3 strain cells, which are the active ingredient, it can extremely effectively exert various physiological activities, including the effect of reducing intestinal permeability and the effect of preventing and / or improving liver dysfunction.

[0054] The composition for preventing and / or suppressing increased intestinal permeability, or the composition for preventing decreased liver function and / or improving liver function, is preferably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as the respective effects are achieved.

[0055] The method of use of the composition for preventing and / or suppressing increased intestinal permeability or the composition for preventing liver function decline and / or improving liver function is not particularly limited and can be selected appropriately depending on the purpose. Examples include oral administration, parenteral administration, and topical administration, with oral administration being preferred.

[0056] The oral composition is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include orally administered agents, foods and beverages. Here, foods and beverages refer to those that are unlikely to be harmful to human health and are ingested orally or by administration through the digestive tract in normal social life, and are not limited to administrative classifications such as foods, medicines, and quasi-drugs. Therefore, the foods and beverages refer to a wide range of orally ingested general foods, health foods (functional foods and beverages), health functional foods (foods for specified health uses, foods with nutrient functions, foods with functional claims), quasi-drugs, medicines, etc.

[0057] The type of oral composition is not particularly limited and can be appropriately selected depending on the purpose. Examples include beverages such as tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, alcoholic drinks, coffee drinks, and coffee-containing soft drinks (including concentrated liquids and powders for adjusting these beverages); frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, vermicelli, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; sweets such as candy, candy, gum, chocolate, candy tablets, snacks, biscuits, jelly, jam, cream, baked goods, and bread; seafood such as crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oysters, saury, squid, ark shells, scallops, abalone, sea urchin, salmon roe, and tokobushi sea bream; and kamaboko and ham. processed seafood and livestock foods such as sausages and other dairy products; processed milk, fermented milk, and other dairy products; oils and fats and oil-processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; condiments such as sauces and dressings; retort pouch foods such as curry, stew, oyakodon, rice porridge, rice porridge, Chinese rice bowl, pork cutlet bowl, tempura bowl, eel bowl, hayashi rice, oden, mapo dolphin, beef bowl, meat sauce, egg soup, omelet rice, gyoza, shumai, hamburger steak, and meatballs; side dishes such as salads and pickles; health, beauty, and nutritional supplements in various forms; pharmaceuticals and quasi-drugs such as tablets, powders, capsules, granules, extracts, syrups, drinks, lozenges, and mouthwash; and oral fresheners and toothpastes used in the oral cavity.

[0058] The method for producing the composition for preventing and / or suppressing increased intestinal permeability or the composition for preventing liver function decline and / or improving liver function is not particularly limited, and can be selected appropriately depending on the form of the composition for preventing and / or suppressing increased intestinal permeability or the composition for preventing liver function decline and / or improving liver function.

[0059] The amount, period of use, interval of use, etc. of the composition for preventing and / or suppressing increased intestinal permeability or the composition for preventing liver function decline and / or improving liver function are not particularly limited and can be selected appropriately depending on the purpose.

[0060] As described above, the agent for preventing and / or suppressing increased intestinal permeability and the composition for preventing and / or suppressing increased intestinal permeability of the present invention have excellent preventive and / or suppressive effects on increased intestinal permeability. Therefore, the present invention also relates to a method for preventing and / or suppressing increased intestinal permeability, which comprises administering to an individual at least one of the agent for preventing and / or suppressing increased intestinal permeability and the composition for preventing and / or suppressing increased intestinal permeability.

[0061] As described above, the agent for preventing liver function decline and / or improving liver function and the composition for preventing liver function decline and / or improving liver function of the present invention have excellent effects of preventing liver function decline and / or improving liver function. Therefore, the present invention also relates to a method for preventing liver function decline and / or improving liver function, which comprises administering to an individual at least one of the agent for preventing liver function decline and / or improving liver function and the composition for preventing liver function decline and / or improving liver function.

[0062] Test examples and formulation examples of the present invention will be explained below, but the present invention is not limited to these test examples and formulation examples.

[0063] (Test Example 1) <Production of Food Containing Lactobacillus plantarum Strain 22A-3 (FERM BP-21411)> Hard capsules having the following composition were produced as a food containing Lactobacillus plantarum strain 22A-3 (FERM BP-21411) by a conventional method. Note that No. 1 hard gelatin capsules were used as the capsules. <Composition in 1 capsule (210 mg)> Lactobacillus plantarum strain 22A-3-containing preparation (Smart Lactic Acid Bacteria (registered trademark) Killed Bacteria MF (Maruzen Pharmaceutical Co., Ltd.), lactic acid bacteria count: 1.0 x 10 １１ (pieces / g or more) 40.0 mg Corn starch 70.0 mg Lactose 80.0 mg Calcium lactate 10.0 mg Hydroxypropyl cellulose (HPC-L) 10.0 mg

[0064] <Test Method> Subjects (12 people, average age 54 years) were instructed to take one capsule of the food containing Lactobacillus plantarum 22A-3 strain daily for 12 weeks.

[0065] - Measurement - Blood samples were collected from the subjects before, 8 weeks after, and 12 weeks after ingestion of the food containing Lactobacillus plantarum 22A-3 strain. The zonulin concentration in the collected serum was determined using IDK (registered trademark) Zonulin ELISA (manufactured by Immundiagnostik AG). The results (average values ​​for 12 subjects) are shown in Figure 1.

[0066] As shown in Figure 1, it was confirmed that the intake of a food containing Lactobacillus plantarum strain 22A-3 reduced the zonulin concentration in the blood. Therefore, it was confirmed that Lactobacillus plantarum strain 22A-3 has an intestinal permeability reducing effect and can prevent and / or suppress the increase in intestinal permeability. Furthermore, since the increase in intestinal permeability leads to a decrease in liver function, it is believed that the present invention can also prevent the decrease in liver function and / or improve liver function.

[0067] Test Example 2 Production of Food Containing Lactobacillus plantarum Strain 22A-3 (FERM BP-21411) In the same manner as in Test Example 1, a food containing Lactobacillus plantarum strain 22A-3 (FERM BP-21411) was produced.

[0068] <Production of Placebo Food> A placebo food was produced in the same manner as in the Lactobacillus plantarum 22A-3 strain (FERM BP-21411)-containing food, except that dextrin was used instead of 40.0 mg of the Lactobacillus plantarum 22A-3 strain-containing preparation.

[0069] <Test method> The test was a randomized, placebo-controlled, double-blind, parallel-group comparative study in which 60 subjects (2 groups of 30 subjects) were asked to take one capsule per day of either a food containing Lactobacillus plantarum 22A-3 strain (hereinafter sometimes referred to as the "test food group") or a placebo food (hereinafter sometimes referred to as the "placebo food group") for 12 weeks.

[0070] - Measurement - Blood samples were taken from the subjects before, 6 weeks after, and 12 weeks after ingestion of the food containing Lactobacillus plantarum 22A-3 strain or the placebo food. The results of the blood tests regarding liver function are shown in Tables 1 to 3 and Figures 2 to 4.

[0071] The measured values ​​and the changes from the measured values ​​before ingestion are shown in Tables 1 to 3. Figures 2 to 4 show the changes from the measured values ​​before ingestion to the measured values ​​6 and 12 weeks after ingestion of the test foods. Figure 2 shows the changes in the measured values ​​of alanine aminotransferase (ALT), Figure 3 shows the changes in the measured values ​​of aspartate aminotransferase (AST), and Figure 4 shows the changes in the measured values ​​of γ-glutamyltranspeptidase (γ-GTP).

[0072]

[0073]

[0074]

[0075] As shown in Tables 1 to 3 and Figures 2 to 4, in the placebo food group, ALT, AST, and γ-GTP all tended to increase compared to before ingestion of the test food, whereas in the test food group, ALT, AST, and γ-GTP all tended to decrease compared to before ingestion of the test food. Therefore, it was confirmed that the present invention can prevent decline in liver function and / or improve liver function.

[0076] Formulation Example 1 Tablets (daily intake) having the following composition were produced by a conventional method: Lactobacillus plantarum 22A-3 strain-containing preparation (Smart Lactic Acid Bacteria (registered trademark) powder (manufactured by Maruzen Pharmaceuticals Co., Ltd.)) 20.0 mg Dolomite (containing 20% ​​calcium and 10% magnesium) 83.4 mg Casein phosphopeptide 16.7 mg Vitamin C 33.4 mg Maltitol 136.8 mg Collagen 12.7 mg Sucrose fatty acid ester 12.0 mg

[0077] Formulation Example 2 An oral liquid formulation (daily intake amount) having the following composition was produced by a conventional method. <Composition per ampoule (100 mL per ampoule)> Lactobacillus plantarum 22A-3 strain-containing formulation (Smart Lactic Acid Bacteria (registered trademark) killed cells MF (Maruzen Pharmaceuticals Co., Ltd.)) 0.04% by mass Sorbitol 12.0% by mass Sodium benzoate 0.1% by mass Flavoring 1.0% by mass Calcium sulfate 0.5% by mass Purified water balance

[0078] Formulation Example 3 A soft drink (daily intake amount) having the following composition was produced by a conventional method.・Lactobacillus plantarum 22A-3 strain-containing preparation (Smart Lactic Acid Bacteria (registered trademark) powder (Maruzen Pharmaceuticals Co., Ltd.)) 0.02g ・Royal jelly 3.0g ・Water-soluble collagen 8.0g ・Job's tears extract 1.0g ・Korean ginseng extract 1.0g ・Placenta extract 1.0g ・Pueraria extract 1.0g ・Purple yam extract 1.0g ・Oligosaccharides 5.0g ・Sucrose 10.0g ・Prune juice 2.0g ・Pomegranate juice 5.0g ・Grapefruit juice 10.0g ・Vitamin C 1.0g ・Grapefruit flavor 1.0g ・Water 1.0g Remainder (total amount is 100g)

[0079] (Formulation Example 4) Capsules (daily intake) having the following composition were produced by a conventional method. No. 1 hard gelatin capsules were used. <Composition per capsule (210 mg)> Lactobacillus plantarum 22A-3 strain-containing preparation (Smart Lactic Acid Bacteria (registered trademark) killed cells MF (Maruzen Pharmaceuticals Co., Ltd.)) 40.0 mg Corn starch 70.0 mg Lactose 80.0 mg Calcium lactate 10.0 mg Hydroxypropyl cellulose (HPC-L) 10.0 mg

[0080] This application claims priority based on Japanese Patent Application No. 2023-188213 filed on November 2, 2023 and Japanese Patent Application No. 2024-103752 filed on June 27, 2024. The entire contents of Japanese Patent Application No. 2023-188213 and Japanese Patent Application No. 2024-103752 are incorporated by reference into this application.

[0081] FERM BP-21411

Claims

1. A preventive and / or inhibitor for increased intestinal permeability, which is used for preventing and / or inhibiting increased intestinal permeability and is characterized in that it contains Lactobacillus plantarum 22A-3 strain (FERM BP-21411) cells.

2. A composition for preventing and / or suppressing increased intestinal permeability, comprising the agent for preventing and / or suppressing increased intestinal permeability as described in claim 1.

3. An agent for preventing and / or improving liver function, which is used for preventing and / or improving liver function, and which comprises Lactobacillus plantarum 22A-3 strain (FERM BP-21411) cells.

4. A composition for preventing liver dysfunction and / or improving liver function, comprising the agent for preventing liver dysfunction and / or improving liver function described in claim 3.

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