Gastrointestinal tissue recovery promoter

Abstract

To provide a novel gastrointestinal tissue recovery promoter. [Solution] A gastrointestinal tissue recovery promoter containing β-hydroxybutyric acid as an active ingredient, for promoting the recovery of gastrointestinal tissue. [Effects] By including β-hydroxybutyric acid at a predetermined concentration as an active ingredient, it can promote the recovery of gastrointestinal tissue, thus making it a convenient gastrointestinal tissue recovery promoter.

Description

Technical Field

[0001] The present invention relates to an accelerator for promoting the recovery of gastrointestinal tissue, which has an effect of promoting the recovery of gastrointestinal tissue.

Background Art

[0002] Ulcerative colitis and Crohn's disease, in which the regeneration mechanism of intestinal epithelium is chronically disrupted, are diseases of unknown cause that chronically form erosions and ulcers on the large intestine mucosa and cause diarrhea accompanied by abdominal pain and bloody stools. Currently, there are approximately 220,000 patients with ulcerative colitis in Japan, and the number is increasing year by year. There is no treatment method that can completely cure ulcerative colitis, and continuous treatment is necessary to maintain remission.

[0003] In addition, in intestinal epithelial cells, the system of cell proliferation, differentiation, and cell death is controlled throughout life. However, with aging, the self-renewal ability of gastrointestinal stem cells decreases, leading to a decline in gastrointestinal function. Furthermore, such a decrease in self-renewal ability also affects the repair mechanism of damaged cells.

[0004] Recently, the development of gastrointestinal stem cell activators such as Patent Document 1 has been carried out. Patent Document 1 discloses a gastrointestinal stem cell activator containing royal jelly as an active ingredient.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] The function of activating gastrointestinal stem cells by royal jelly as in Patent Document 1 has been clarified, and the development of agents using it has been carried out. However, the development of agents aimed at promoting the recovery of gastrointestinal tissue by β-hydroxybutyric acid has not been carried out.

[0007] This invention has been made in view of the above-mentioned problems, and its purpose is to provide a novel gastrointestinal tissue recovery promoter. [Means for solving the problem]

[0008] The characteristic configuration of the gastrointestinal tissue recovery promoter according to the present invention, which achieves the above objective, is as follows: Its key feature is that it contains β-hydroxybutyrate as its active ingredient.

[0009] Beta-hydroxybutyric acid and its salts (hereinafter referred to as BHB, and when referred to as BHB, it specifically refers to its monomer) are substances that naturally exist in the human body and therefore have high biocompatibility. For example, they are expected to be used as an alternative energy source to carbohydrates and as health foods.

[0010] In the examples described later, it has been observed that administering BHB to mice tends to promote the recovery of gastrointestinal tissue.

[0011] Therefore, the gastrointestinal tissue recovery promoter of the present invention can promote the recovery of gastrointestinal tissue by containing a predetermined concentration of β-hydroxybutyric acid as an active ingredient, thus making it a simple gastrointestinal tissue recovery promoter.

[0012] Further characteristic features of the gastrointestinal tissue recovery promoter according to the present invention are: The aforementioned β-hydroxybutyrate is administered at a dose of 0.01 g / kg body weight to 50 g / kg body weight per day.

[0013] By keeping the dosage of β-hydroxybutyrate within the above range, it is possible to achieve a recovery-promoting effect on gastrointestinal tissues without causing ketoacidosis.

[0014] Further characteristic features of the gastrointestinal tissue recovery promoter according to the present invention are: The aforementioned digestive tract tissue is either the small intestine or the large intestine. [Brief explanation of the drawing]

[0015] [Figure 1] This figure shows the results of measuring the number of crypts in mice administered β-hydroxybutyrate. [Figure 2] This figure shows the results of hematoxylin-eosin staining of the intestinal tract in mice administered β-hydroxybutyrate. [Modes for carrying out the invention]

[0016] The following describes a gastrointestinal tissue recovery promoter according to an embodiment of the present invention, but the present invention is not limited to the following embodiments.

[0017] In this specification, "active ingredient" means any component that is delivered to the gastrointestinal tissue by the gastrointestinal tissue recovery promoter of the present invention and exhibits a predetermined activity such as promoting the elongation of crypts in damaged intestinal crypts.

[0018] In this specification, "gastrointestinal tissue recovery promoter" means an agent that, when ingested, can promote the recovery of gastrointestinal tissue. Furthermore, in this specification, "gastrointestinal tissue recovery" means the recovery of gastrointestinal tissue due to, for example, the elongation of intestinal crypts or the proliferation of cells in intestinal crypts. Furthermore, in this specification, "gastrointestinal tissue" means the small or large intestine of a human.

[0019] Beta-hydroxybutyric acid (BHB) can be obtained, for example, by carrying out a fermentation process with the addition of BHB-producing Halomonas bacteria, separating and removing the Halomonas bacteria from the resulting fermentation liquid, and then purifying it. The fermentation process can be carried out by adding BHB-producing Halomonas bacteria directly to a raw material liquid containing a carbohydrate nutrient source such as fruit juice, and then sequentially carrying out aerobic fermentation and microaerobic fermentation (Japanese Patent Publication No. 2013-081403). As a result, the carbohydrates are converted into BHB and produced in the fermentation liquid. The produced BHB is then separated and purified by conventional methods such as membrane separation and used as pure BHB.

[0020] BHB, which is contained as an active ingredient of the gastrointestinal tissue recovery promoter of the present invention, may be a salt of BHB. Examples of the salt of BHB include potassium salt, sodium salt, calcium salt, magnesium salt, and the like. Further, either one or both of BHB or a salt of BHB may be contained.

[0021] The gastrointestinal tissue recovery promoter of the present invention may contain only BHB or a salt of BHB, or may contain other components. As the other components, as long as the effects of the present invention are not impaired, physiologically or pharmaceutically acceptable additives that can be normally used, that is, minerals, vitamins, amino acids, fatty acids, sweeteners, coloring agents, fragrances, thickeners, preservatives, antiseptics, stabilizers, etc. can also be blended.

[0022] In the gastrointestinal tissue recovery promoter of the present invention, BHB or a salt of BHB can be used at a dose of 0.01 g / kg body weight or more and 50 g / kg body weight or less per day, more preferably at a dose of 0.05 g / kg body weight or more and 30 g / kg body weight or less, still more preferably at a dose of 0.1 g / kg body weight or more and 20 g / kg body weight or less, even more preferably at a dose of 0.3 g / kg body weight or more and 10 g / kg body weight or less, and particularly preferably at a dose of 0.5 g / kg body weight or more and 8 g / kg body weight or less. The dose can be appropriately set within the above range according to factors such as the health condition of the person ingesting, the administration method, and the combination with other agents.

[0023] If the dose of BHB or a salt of BHB is within the above range, the effect of promoting the recovery of gastrointestinal tissue can be obtained without entering a ketosis state. Further, if it exceeds 50 g / kg body weight, it will enter a ketosis state, which is dangerous.

[0024] The gastrointestinal tissue recovery promoter of the present invention can be used as a pharmaceutical, quasi-drug, and food composition itself, or added to pharmaceuticals, quasi-drugs, and food compositions. Preferably, the food composition is one in which the tertiary function (physical condition regulation function) of the food is emphasized. Examples of foods in which the tertiary function of the food is emphasized include health foods, foods with functional claims, nutritional supplements, supplements, and foods for specified health uses.

[0025] The amount of the gastrointestinal tissue recovery promoter of the present invention in pharmaceuticals, quasi-drugs, and food compositions should be appropriately set according to factors such as the type of pharmaceutical, quasi-drug, and food composition, the health condition of the person taking it, the method of administration, and combinations with other agents, so that the amount of active ingredient ingested per day is within the range described above.

[0026] The gastrointestinal tissue recovery promoter of the present invention may be taken orally as is, or it may be formulated into capsules, tablets, granules, powders, coatings, sugar coatings, emulsions, liquids, syrups, etc., and taken orally.

[0027] The gastrointestinal tissue recovery promoter of the present invention is preferably provided as a pharmaceutical composition or functional food containing BHB as an active ingredient. In particular, in the form of a functional food, it can be taken orally on a daily basis, and is therefore considered to be an easy way to improve the intestinal environment.

[0028] The functional foods in question refer to those provided in the form of, for example, Foods for Specified Health Uses (foods containing health-promoting ingredients that affect the physiological functions of the body and for which specific effects are recognized), Foods with Nutrient Function Claims (foods used to supplement or complement nutrients), Health Supplements, and Nutritional Supplements. The proportion of the gastrointestinal tissue recovery promoter of the present invention contained in the functional foods in question may be appropriately determined by those skilled in the art.

[0029] The gastrointestinal tissue recovery promoter of the present invention may be mixed with pharmaceutically and pharmacologically acceptable additives when formulated. By containing various pharmaceutically acceptable additives, it can be provided in various forms as a pharmaceutical, food, or animal feed.

[0030] Examples of such additives include excipients such as lactose, sucrose, glucose, and sorbitol; binders such as starch and gelatin; lubricants such as stearic acid, hydrogenated oil, and magnesium stearate; disintegrants such as potato starch; humectants such as sodium lauryl sulfate; stabilizers such as polyethylene glycol; surfactants such as sodium lauryl sulfate and sorbitan monofatty acid ester; preservatives such as benzyl alcohol, ethyl parahydroxybenzoate, and benzoic acid; sweeteners such as stevia and aspartame; acidulants such as succinic acid and malic acid; and vegetable oils. Examples of ingredients include, but are not limited to, various fats and oils such as animal fats, herbal medicines such as royal jelly and ginseng, amino acids such as glutamine, cysteine, leucine, and arginine, polyhydric alcohols such as ethylene glycol and polyethylene glycol, natural polymers such as agar, gelatin, xanthan gum, starch, and dextrin, vitamins such as vitamin C and B vitamins, minerals such as calcium, magnesium, zinc, and iron, dietary fiber such as mannan, pectin, and hemicellulose, pH adjusters, antioxidants, flavoring agents, fragrances, and coloring agents.

[0031] Thus, by ingesting the gastrointestinal tissue recovery promoter of the present invention, it is expected that the recovery of gastrointestinal tissue can be easily promoted.

[0032] In other words, by administering the gastrointestinal tissue recovery promoter of the present invention to humans or animals, the gastrointestinal tissue can be restored.

[0033] The amount of the gastrointestinal tissue recovery promoter of the present invention can be varied depending on the age, weight, route of administration, and frequency of administration of the human or animal being administered, and various amounts can be set within the above concentration range. Furthermore, the gastrointestinal tissue recovery promoter of the present invention may be used in combination with other pharmaceuticals, treatments, or preventive methods.

[0034] The gastrointestinal tissue recovery promoter of the present invention contains BHB, a substance naturally present in the human body, as its active ingredient, making it highly safe and easily accessible by oral ingestion.

[0035] Furthermore, BHB, which is included as an active ingredient, is a stable compound and suitable for processing food products, so it can be added to various foods and consumed continuously. [Examples]

[0036] The present invention will be described in more detail below based on examples, but the present invention is not limited to the following examples.

[0037] Three-month-old mice were given free access to a 4% by mass aqueous solution of BHB for two weeks. Each mouse consumed approximately 4 mL of water per day, resulting in a BHB intake of approximately 0.18 g per day (4 mL / day × 4% × 1.126 g / mL). Feeding was also ad libitum.

[0038] Subsequently, whole-body X-ray irradiation was performed with a total radiation dose of 15 Gy. Five days after irradiation, the upper small intestine was collected and stained with hematoxylin eosin (HE staining). The number of crypts in an 8 mm section of the intestine was then counted and calculated as the number of viable crypts per 1 mm of intestine. The results are shown in Figures 1 and 2.

[0039] Intestinal tissue damaged by radiation is repaired to its normal state by a tissue regeneration mechanism in the crypts. As shown in Figure 1, mice not administered BHB (control) had a crypt count of 14.5 / mm, while mice administered BHB (BHB) had a crypt count of 22.3 / mm. In the case of unirradiated mice, the crypt count was 20-25 / mm. This indicates that mice administered BHB had a higher crypt count than the control, suggesting accelerated recovery of the gastrointestinal tissue. Figure 2 shows the results of HE staining of the upper small intestine; the darker the color, the higher the crypt count, indicating accelerated recovery of the gastrointestinal tissue. Figure 2 also shows that the BHB group had a higher crypt count than the control, indicating that BHB administration promotes recovery of the gastrointestinal tissue.

[0040] <Another Embodiment>

[0041] Furthermore, the configurations disclosed in the above embodiments can be applied in combination with configurations disclosed in other embodiments, provided that no inconsistencies arise. Moreover, the embodiments disclosed herein are illustrative, and the embodiments of the present invention are not limited thereto, and can be modified as appropriate without departing from the object of the present invention.

Claims

1. A gastrointestinal tissue recovery promoter containing β-hydroxybutyric acid as the active ingredient, for promoting the recovery of gastrointestinal tissue.

2. The gastrointestinal tissue recovery promoter according to claim 1, wherein the β-hydroxybutyric acid is administered at a dose of 0.01 g / kg of body weight or more and 50 g / kg of body weight or less per day.

3. The gastrointestinal tissue recovery promoter according to claim 1 or 2, wherein the gastrointestinal tissue is the small intestine or the large intestine.

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