Composition for IAP activation

Abstract

To provide a novel composition for IAP activation.SOLUTION: The present invention provides a composition for IAP activation, a pharmaceutical composition for IAP activation, a food composition for IAP activation, or a feed composition for IAP activation, each containing D-tryptophan and / or tryptophan metabolite as an active ingredient. Further provided are a composition for prevention or improvement of intestinal inflammation, a pharmaceutical composition for prevention or improvement of intestinal inflammation, a food composition for prevention or improvement of intestinal inflammation, or a feed composition for prevention or improvement of intestinal inflammation, each containing the composition for IAP activation.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a component that enhances intestinal alkaline phosphatase (IAP) activity. [Background technology]

[0002] Intestinal alkaline phosphatase (IAP) is a dephosphorylating enzyme expressed on the small intestinal brush border. IAP detoxifies inflammation-inducing substances (e.g., lipopolysaccharides and flagellin) derived from enterobacteria in the intestinal lumen, thereby preventing inflammation in the intestinal tract (Non-Patent Documents 1 and 2).

[0003] Decreased IAP activity has been reported to be involved in various diseases, including diabetes, chronic renal failure, metabolic syndrome, inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), necrotizing enterocolitis (NEC), sepsis, and antibiotic-associated diarrhea (Non-Patent Documents 1 and 2). Therefore, activating IAP is expected to have preventive and ameliorative effects on these diseases.

[0004] Various substances have been reported to activate IAP. Examples include hormones such as adrenocorticotropic hormone and thyroid hormone, lipids such as long-chain and medium-chain triacylglycerols, carbohydrates such as starch, cellulose, and oligosaccharides, as well as amino acids, peptides, vitamins, and minerals (Non-Patent Documents 1 and 2). Some of these components have been suggested to have inhibitory effects on the various diseases mentioned above (Non-Patent Documents 1 and 2). Since food components have been reported to have the ability to activate IAP, it is thought that improving the nutritional composition of one's daily diet can maintain high IAP activity and prevent various diseases.

[0005] Meanwhile, tryptophan, an essential amino acid, is known to undergo various metabolisms both in and outside the body and to exert physiological activities. For example, it has been reported that tryptophan is converted into serotonin and melatonin in the body, which contributes to sleep, inducing, and sedative effects, and that tryptophan is converted into tryptamine and indole-3-aldehyde by intestinal bacteria, which contributes to maintaining homeostasis of the immune system (Non-Patent Document 3). However, Non-Patent Document 3 does not describe the effect of tryptophan and its metabolites on IAP activity in the intestinal tract. In a paper evaluating the effect of tryptophan on the enzymatic reaction of IAP, it has been reported that L-tryptophan acts as an inhibitor of human IAP (Non-Patent Document 4), and tryptophan has been considered a substance that acts to suppress IAP activity. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Lalles JP. Recent advances in intestinal alkaline phosphatase, inflammation, and nutrition. Nutr Rev.2019 October;77(10):710-724. [Non-patent document 2] Lalles JP. Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutr Rev. 2010 Jun;68(6):323-32. [Non-patent document 3] Agus A., Planchais J., & Sokol H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018 Jun 13;23(6):716-724. [Non-patent document 4] Lin CW, Sie HG, & Fishman WH L-tryptophan. A non-allosteric organ-specific uncompetitive inhibitor of human placental alkaline phosphatase. Biochem J. 1971 Sep;124(3):509-16. Summary of the Invention [Problem to be solved by the invention]

[0007] An objective of the present invention is to provide a novel composition for activating IAP. [Means for solving the problem]

[0008] As a result of extensive research to solve the above-mentioned problems, the inventors have discovered that D-tryptophan and tryptophan metabolites have strong IAP activation activity, and that the use of D-tryptophan and / or tryptophan metabolites can produce a composition with high IAP activation ability.

[0009] Specifically, the present invention is as follows: The term "composition" as used herein includes preparations, foods and drinks, feeds and other substances that can be ingested by animals (including humans). <1> A composition for activating IAP, which contains D-tryptophan and / or a tryptophan metabolite as an active ingredient. <2> The concentration of D-tryptophan is 0.05% by mass or more. <1> The composition for activating IAP described above. <3> The tryptophan metabolite is 3-indoleacrylic acid. <1> The composition for activating IAP described above. <4> The concentration of 3-indoleacrylic acid is 0.001563% by mass or more. <3> The composition for activating IAP described above. <5> <1> ~ <4> A composition for preventing or ameliorating intestinal inflammation, comprising the composition for activating IAP described in any one of the above. <6> <1> ~ <4> A pharmaceutical composition for IAP activation, a food composition for IAP activation, or a feed composition for IAP activation, comprising the composition for IAP activation according to any one of the above. <7> <1> ~ <4> A pharmaceutical composition for preventing or ameliorating intestinal inflammation, a food composition for preventing or ameliorating intestinal inflammation, or a feed composition for preventing or ameliorating intestinal inflammation, comprising any one of the compositions for activating IAP described above. [Effects of the Invention]

[0010] According to the present invention, a composition for activating IAP containing D-tryptophan and / or a tryptophan metabolite as an active ingredient can be provided. [Brief explanation of the drawings]

[0011] [Figure 1] 1 is a graph showing IAP activity (U / mg protein) when 125 to 500 μg / ml of L-tryptophan or 125 to 500 μg / ml of D-tryptophan was added to the human colon cancer-derived cell line Caco-2, which had been cultured for two weeks, and then cultured for one week. [Figure 2] 1 is a graph showing IAP activity (U / mg protein) when 1.95 to 250 mM 3-indoleacrylic acid was added to human colon cancer-derived cell line Caco-2 that had been cultured for two weeks and then cultured for one week. DETAILED DESCRIPTION OF THE INVENTION

[0012] The composition for activating IAP of the present invention is characterized by containing D-tryptophan and / or a tryptophan metabolite as an active ingredient. The present invention also relates to pharmaceutical compositions, food compositions, and feed compositions for activating IAP, which contain the composition. Furthermore, the present invention relates to compositions for preventing or ameliorating intestinal inflammation, which contain the composition for activating IAP. The active ingredients and compositions for each purpose are described below.

[0013] (D-tryptophan) D-tryptophan, which is an active ingredient of the present invention, refers to the D-form of tryptophan, an amino acid, and has an IAP activating effect.

[0014] The source of the D-tryptophan used in the present invention is not particularly limited. It can be obtained by extraction, concentration, purification, etc. from raw materials, foods, microorganisms, etc., or by fermentation using microorganisms, chemical synthesis, etc. These methods can be appropriately selected based on the desired purity of D-tryptophan and production costs. D-tryptophan may be in a free state or bound to peptides and / or proteins. It may also be a salt or hydrate. Examples of salts include salts with organic acids, inorganic acids, inorganic bases, etc. It may be a chemically synthesized product, a semi-synthetic product, or a natural product derived from animals, plants, or microorganisms. Natural materials containing natural products may be used as a source and incorporated directly into the composition of the present invention. Here, "natural products" refers to products extracted from natural materials containing D-tryptophan by known methods, crudely purified products, or products further purified from such products. The D-tryptophan used in the present invention may also contain L-tryptophan, regardless of its optical purity. The D-tryptophan used in the present invention may also be a commercially available product. Examples of such commercially available products include those from Nacalai Tesque, Inc., Tokyo Chemical Industry Co., Ltd., and Fujifilm Wako Pure Chemical Industries, Ltd.

[0015] The composition for activating IAP of the present invention, which contains D-tryptophan as an active ingredient, preferably contains 0.05% by mass or more of D-tryptophan, more preferably 0.1% by mass or more. The upper limit of the content is not particularly limited, but examples include 10% or less and 5% or less. The content ranges from 0.05 to 10% by mass, with 0.1 to 5% by mass being preferred.

[0016] (tryptophan metabolites) The tryptophan metabolite, which is an active ingredient of the present invention, refers to a substance produced from L-tryptophan and / or D-tryptophan through metabolism by mammals, including humans, and / or microorganisms, and has an IAP activating effect. Specifically, these include melatonin, N-acetylserotonin, serotonin, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, picolinic acid, quinolinic acid, indole-3-pyruvic acid, indole-3-lactic acid, and 3-indole acrylic acid. Examples of tryptophan metabolites include, but are not limited to, 3-indoleacrylic acid, indole-3-propionic acid, indole, tryptamine, indole-3-acetaldehyde, tryptophol, indole-3-acetamide, indole-3-acetic acid, and indole-3-aldehyde. Of the above, the tryptophan metabolite used in the present invention is preferably 3-indoleacrylic acid.

[0017] The tryptophan metabolites used in the present invention may be derived from fermentation using microorganisms, or may be synthetic, semi-synthetic, or natural. Alternatively, natural materials containing natural products may be used as a supply source and incorporated directly into the composition of the present invention. Here, "natural products" refers to products extracted from natural materials containing tryptophan metabolites by known methods, crudely purified products, or products further purified from these. Alternatively, the tryptophan metabolites used in the present invention may be commercially available products.

[0018] A composition for activating IAP containing a tryptophan metabolite as an active ingredient preferably contains 0.001563% by mass or more of the tryptophan metabolite, and particularly preferably 0.003125% by mass or more. The upper limit of the content is not particularly limited, but examples include 1% by mass or less or 0.5% by mass or less. The content ranges from 0.005 to 1% by mass, with 0.01 to 0.5% by mass being preferred. Furthermore, compositions for activating IAP containing 3-indoleacrylic acid as an active ingredient preferably contain 0.001563% by mass or more of 3-indoleacrylic acid, and particularly preferably 0.003125% by mass or more. The upper limit of the content is not particularly limited, but examples include 1% by mass or less and 0.5% by mass or less. The content ranges from 0.005 to 1% by mass, with 0.01 to 0.5% by mass being preferred.

[0019] (How to use) As described above, the compositions of the present invention can contain as active ingredients D-tryptophan and / or tryptophan metabolites derived from microbial fermentation, synthetic products, semisynthetic products, or natural products, and therefore can be widely used as raw materials for pharmaceuticals, foods, beverages, and feeds.

[0020] (Pharmaceutical composition for IAP activation) When the IAP activating composition of the present invention is formulated as a pharmaceutical, it can be appropriately mixed with pharmaceutically acceptable excipients, stabilizers, flavoring agents, etc., and then concentrated or lyophilized. These dried, concentrated, and paste-like forms are also included. Furthermore, the composition can be formulated by mixing excipients, binders, disintegrants, lubricants, flavoring agents, suspending agents, coating agents, and any other optional agents within the scope of not interfering with the IAP activating activity of the composition. Possible dosage forms include tablets, capsules, granules, powders, dusting agents, and syrups, and these are preferably administered orally. They can also be administered parenterally in parenteral forms such as gastrostomy tubes, injections, infusions, and patches.

[0021] (Food composition for IAP activation) The IAP-activating composition of the present invention may be incorporated into any food or beverage, or may be added to raw materials during the manufacturing process of the food or beverage. Examples of food or beverage include, but are not limited to, dairy products such as cheese, fermented milk, dairy lactic acid bacteria drinks, lactic acid bacteria drinks, butter, margarine, and other dairy products; milk drinks, fruit juice drinks, soft drinks, and other beverages; egg products such as jelly, candy, pudding, and mayonnaise; confectioneries and breads such as butter cake; various types of powdered milk; infant foods; and nutritional compositions. The D-tryptophan to be incorporated into a food composition may be present in any amount that does not impair the flavor of the food and is expected to have an IAP-activating effect. For example, the amount may be 0.05 to 10% by mass, with 0.1 to 5% by mass being preferred. Furthermore, the amount of 3-indoleacrylic acid, a tryptophan metabolite, may be present in an amount of 0.005 to 1% by mass, with 0.01 to 0.5% by mass being preferred.

[0022] The classification of the above-mentioned food and drink is not particularly limited, and it can be used as a general food, a health functional food, a food for special uses, etc. Furthermore, as a health functional food, it can be used as a food for specified health uses, a food with nutrient function claims, a food with functional claims, etc.

[0023] When indicating the uses of the IAP activating composition of the present invention, examples include indications stipulated by various laws, enforcement regulations, guidelines, etc. Indications of use include indications on packaging such as wrapping and containers, as well as indications on advertising media such as pamphlets.

[0024] (Feed composition for IAP activation) The IAP activating composition of the present invention can be incorporated into feed. It may be incorporated into any feed, as with the aforementioned foods and beverages, or may be added to raw materials during the feed production process. The D-tryptophan to be incorporated into the feed composition may be present in any amount that does not impair the flavor of the feed and is expected to have an IAP activating effect, for example, in an amount of 0.05 to 10% by mass, with 0.1 to 5% by mass being a preferred range. Furthermore, the amount of 3-indoleacrylic acid as a tryptophan metabolite may be present in an amount of, for example, 0.005 to 1% by mass, with 0.01 to 0.5% by mass being a preferred range.

[0025] (Target of administration) The recipient of the IAP activating composition of the present invention is not particularly limited, and may be a human or a non-human animal (e.g., a dog, cat, horse, or rabbit). When the recipient is a human, the composition may be administered to a minor under 20 years of age, an adult, or an elderly person 65 years of age or older. The recipient of the IAP activating composition of the present invention may be a healthy subject or a subject with a condition requiring IAP activation. Specific examples of subjects with a condition requiring IAP activation include subjects diagnosed with diabetes, chronic renal failure, metabolic syndrome, inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), necrotizing enterocolitis (NEC), sepsis, antibiotic-associated diarrhea, etc., or subjects with low IAP activity. Further examples include subjects without the above symptoms who are hoping to prevent intestinal inflammation.

[0026] (Dosage / Intake) When incorporating D-tryptophan and / or tryptophan metabolites, the active ingredients of the present invention, into compositions for IAP activation, food and beverage compositions for IAP activation, feed compositions for IAP activation, and pharmaceutical compositions for IAP activation, the dosage can be determined taking into account the symptoms, age, and other factors of the recipient. For example, for adults, the amount of each composition can be adjusted to ensure that 0.01 to 1 g of D-tryptophan (free form equivalent) is ingested per day. Furthermore, when 3-indoleacrylic acid is incorporated as a tryptophan metabolite, the amount of each composition can be adjusted to ensure that 0.001 to 0.1 g is ingested per day. When both D-tryptophan and a tryptophan metabolite are incorporated, the dosage ranges described above can be adjusted according to the respective proportions. By ingesting compositions formulated in this manner, the desired effects can be expected.

[0027] (Method for assessing IAP activity) The evaluation can be performed by the method described in the Examples, that is, the method using the human colon cancer-derived cell line Caco-2. Specifically, the method is as follows. (1) Caco-2 cells are cultured on collagen-coated (Nitta Gelatin) 48-well plates. The culture medium is high-glucose DMEM (Nacalai Tesque) containing 10% FBS (Gibco), 1% NEAA (Nacalai Tesque), and 1% penicillin-streptomycin (Gibco). The cells are cultured at 37°C and 5% CO2. (2) 0.5 × 10 Caco-2 cells were plated on a collagen-coated 48-well plate. 5 The cells are seeded at 1000 cells / well, and the day they become confluent is considered to be day 0 of culture. Culture is continued for 2 weeks with medium changes every 2-3 days. (3) After two weeks, the medium is replaced with medium containing samples dissolved at various concentrations, and the cells are cultured for seven days, with the medium being replaced every two to three days. (4) After adding the sample, the cells were cultured for 7 days and washed three times with physiological saline. 200 μl / well of 1% Triton-X, 1 mM PMSF, and 10 mM TBS (pH 7.3) was added to lyse the cells. The entire cell lysate was collected in a 1.5 ml tube and sonicated on ice (on time 15 seconds, 30% amp). The cells were centrifuged at 4,800 × g for 5 minutes at 4°C, and the supernatant was collected. The collected supernatant was used as the crude enzyme extract and stored at -80°C until use in the assay. (5) IAP activity of crude enzyme extracts was determined by Pierce TM Measurements were performed using the PNPP Substrate Kit (37620, Thermo Fisher Scientific). Bacterial alkaline phosphatase (BAP, Takara) serially diluted with 1% Triton-X, 1 mM PMSF, and 10 mM TBS (pH 7.3) for the calibration curve, or a 10-fold diluted sample, was added to a 96-well plate at 10 μl / well. PNPP substrate solution was added at 90 μl / well, the plate was shaken on a plate shaker, and the plate was left to stand at room temperature in the dark for 30 minutes. After standing, the reaction was stopped by adding 50 μl / well of 2N NaOH, and the absorbance at 405 nm was measured using a Varioskan Flash (Thermo Fisher Scientific). The calibration curve generated from the BAP measurement results was used to calculate IAP activity (U / ml). (6) The protein concentration of the crude enzyme extract was measured using Pierce TM Measurement was performed using a BCA Protein Assay Kit (23225, Thermo Fisher Scientific). IAP activity (U / ml) was corrected for protein concentration (mg / ml), and the corrected value was used as IAP activity (U / mg protein). If the IAP activity (U / mg protein) calculated in this manner is found to increase when the component to be evaluated is contained compared to when it is not contained, then the component to be evaluated can be evaluated as having an IAP activating effect.

[0028] (Composition for preventing or improving intestinal inflammation) The composition for preventing or ameliorating intestinal inflammation of the present invention is a composition containing the above-mentioned composition for activating IAP, and when an effective amount of D-tryptophan and / or a tryptophan metabolite as the active ingredient is ingested, the composition has the effect of preventing or ameliorating intestinal inflammation via IAP activation. [Example]

[0029] The present invention will be described in more detail below based on test examples and examples, but the present invention should not be construed as being limited to these examples, etc. Unless otherwise specified, % indicates % by mass.

[0030] [Test Example 1] Test to evaluate the IAP activation ability of L-tryptophan and D-tryptophan To verify the IAP activating effects of L-tryptophan and D-tryptophan, the following evaluation was performed. 0.5 × 10 Caco-2 cells were cultured on a collagen-coated 48-well plate. 5 The cells were seeded at 1000 cells / well, and the day they became confluent was designated as day 0 of culture. The medium was changed every 2 to 3 days and the cells were cultured for 2 weeks.

[0031] After 2 weeks, the medium was replaced with a medium containing 125 to 500 μg / ml of L-tryptophan (35607-74, Nacalai Tesque) or 125 to 500 μg / ml of D-tryptophan (35605-81, Nacalai Tesque), and the cells were cultured for 7 days, with the medium being replaced every 2 to 3 days.

[0032] After adding the sample, the cells were cultured for 7 days and washed three times with physiological saline. 200 μl / well of 1% Triton-X, 1 mM PMSF, and 10 mM TBS (pH 7.3) was added to lyse the cells. The entire cell lysate was collected in a 1.5 ml tube and sonicated on ice (on time 15 seconds, 30% amp). The cells were centrifuged at 4,800 × g for 5 minutes at 4°C, and the supernatant was collected. The collected supernatant was used as a crude enzyme extract and stored at -80°C until use in the assay.

[0033] IAP activity of crude enzyme extracts was determined using Pierce TM Measurements were performed using the PNPP Substrate Kit (37620, Thermo Fisher Scientific). Bacterial alkaline phosphatase (BAP, Takara) serially diluted in 1% Triton-X, 1 mM PMSF, and 10 mM TBS (pH 7.3) for the calibration curve, or a 10-fold diluted sample, was added to a 96-well plate at 10 μl / well. PNPP substrate solution was added at 90 μl / well, the plate was shaken on a plate shaker, and then allowed to stand at room temperature in the dark for 30 minutes. After standing, the reaction was stopped by adding 50 μl / well of 2N NaOH, and the absorbance at 405 nm was measured using a Varioskan Flash (Thermo Fisher Scientific). IAP activity (U / ml) was calculated using a calibration curve constructed from the BAP measurement results.

[0034] The protein concentration of the crude enzyme extract was determined by Pierce TM Measurement was performed using a BCA Protein Assay Kit (23225, Thermo Fisher Scientific). IAP activity (U / ml) was corrected by protein concentration (mg / ml), and the corrected value was used as IAP activity (U / mg protein).

[0035] Comparison between the control group and the control group was performed using Dunnett's test. The significance level was set at P = 0.05 ( ** P<0.01).

[0036] The results of evaluating the IAP activation ability of L-tryptophan and D-tryptophan are shown in Figure 1. For L-tryptophan, no increase in IAP activity was observed at any concentration between 125 and 500 μg / ml. On the other hand, for D-tryptophan, a significant increase in IAP activity was observed at 500 μg / ml (0.05% by mass). This demonstrates that D-tryptophan has IAP activation ability.

[0037] [Test Example 2] Test to evaluate the IAP activation ability of tryptophan metabolites Since D-tryptophan was found to have the ability to activate IAP, we performed the following evaluation to verify whether 3-indoleacrylic acid, a known intestinal bacterial metabolite of D-tryptophan, also has a similar effect. Caco-2 cells were cultured in a collagen-coated 48-well plate at a concentration of 0.5 × 10 5 The cells were seeded at 1000 cells / well, and the day they became confluent was designated as day 0 of culture. The medium was changed every 2 to 3 days and the cells were cultured for 2 weeks.

[0038] After 2 weeks, the medium was replaced with a medium containing 1.95 to 250 μg / ml of 3-indoleacrylic acid (I0025, Tokyo Chemical Industry Co., Ltd.), and the cells were cultured for 7 days while changing the medium every 2 to 3 days.

[0039] After adding the sample, the cells were cultured for 7 days and washed three times with physiological saline. 200 μl / well of 1% Triton-X, 1 mM PMSF, and 10 mM TBS (pH 7.3) was added to lyse the cells. The entire cell lysate was collected in a 1.5 ml tube and sonicated on ice (on time 15 seconds, 30% amp). The cells were centrifuged at 4,800 × g for 5 minutes at 4°C, and the supernatant was collected. The collected supernatant was used as a crude enzyme extract and stored at -80°C until use in the assay.

[0040] IAP activity of crude enzyme extracts was determined using Pierce TMMeasurements were performed using the PNPP Substrate Kit (37620, Thermo Fisher Scientific). Bacterial alkaline phosphatase (BAP, Takara) serially diluted in 1% Triton-X, 1 mM PMSF, and 10 mM TBS (pH 7.3) for the calibration curve, or a 10-fold diluted sample, was added to a 96-well plate at 10 μl / well. PNPP substrate solution was added at 90 μl / well, the plate was shaken on a plate shaker, and then allowed to stand at room temperature in the dark for 30 minutes. After standing, the reaction was stopped by adding 50 μl / well of 2N NaOH, and the absorbance at 405 nm was measured using a Varioskan Flash (Thermo Fisher Scientific). IAP activity (U / ml) was calculated using a calibration curve constructed from the BAP measurement results.

[0041] The protein concentration of the crude enzyme extract was determined by Pierce TM Measurement was performed using a BCA Protein Assay Kit (23225, Thermo Fisher Scientific). IAP activity (U / ml) was corrected by protein concentration (mg / ml), and the corrected value was used as IAP activity (U / mg protein).

[0042] Comparison between the control group and the control group was performed using Dunnett's test. The significance level was set at P = 0.05 ( * P<0.05, ** P<0.01).

[0043] The results of evaluating the IAP activation ability of 3-indoleacrylic acid are shown in Figure 2. Tests were conducted at concentrations ranging from 1.95 μg / ml to 250 μg / ml. A significant increase in IAP activity was observed at all concentrations above 15.63 μg / ml (0.001563% by mass). This demonstrates that, like D-tryptophan, 3-indoleacrylic acid also has IAP activation ability.

[0044] [Example 1] Production of supplements 1 g of D-tryptophan was mixed with 40 g of an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, and 60 g of an equal mixture of cornstarch and lactose. The mixture was then packed into a stick-shaped bag to produce the IAP-activating supplement of the present invention.

[0045] [Example 2] Production of supplements 0.1 g of 3-indoleacrylic acid was mixed with 40 g of an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, and 60 g of an equal mixture of cornstarch and lactose. The mixture was packed into a stick-shaped bag to produce the IAP-activating supplement of the present invention.

[0046] [Example Product 3] The ingredients were mixed according to the formulation shown in Table 1, filled into a container, and then heat sterilized to produce the IAP activating beverage of the present invention.

[0047] [Table 1]

[0048] [Example Product 4] The ingredients were mixed according to the formulation shown in Table 2, filled into a container, and then heat sterilized to produce the IAP activating beverage of the present invention.

[0049] [Table 2]

[0050] [Example Product 5] 10% skim milk containing 1% D-tryptophan was sterilized and then cooled to 37° C. A yogurt starter was then added, and the mixture was reacted at 37° C. for 72 hours to produce the fermented milk for activating IAP of the present invention.

[0051] [Example Product 6] 10% skim milk containing 0.1% 3-indoleacrylic acid was sterilized and then cooled to 37° C. A yogurt starter was then added, and the mixture was allowed to react at 37° C. for 72 hours to produce the fermented milk for activating IAP of the present invention. [Industrial Applicability]

[0052] It is possible to provide a composition for activating IAP, which contains D-tryptophan and / or a tryptophan metabolite as an active ingredient.

Claims

1. A composition for activating IAP, which contains D-tryptophan and / or a tryptophan metabolite as an active ingredient.

2. 2. The composition for activating IAP according to claim 1, wherein the concentration of D-tryptophan is 0.05% by mass or more.

3. 2. The composition for activating IAP according to claim 1, wherein the tryptophan metabolite is 3-indoleacrylic acid.

4. The composition for activating IAP according to claim 3, wherein the concentration of 3-indoleacrylic acid is 0.001563% by mass or more.

5. A composition for preventing or ameliorating intestinal inflammation, comprising the composition for activating IAP according to any one of claims 1 to 4.

6. A pharmaceutical composition for activating IAP, a food composition for activating IAP, or a feed composition for activating IAP, comprising the composition for activating IAP according to any one of claims 1 to 4.

7. A pharmaceutical composition for preventing or improving intestinal inflammation, a food composition for preventing or improving intestinal inflammation, or a feed composition for preventing or improving intestinal inflammation, comprising the IAP activating composition according to any one of claims 1 to 4.

Images