Irritable bowel syndrome inhibitor

Abstract

To provide a preventive and ameliorative agent with effects in preventing or ameliorating diarrhea or diarrhea-predominant irritable bowel syndrome.SOLUTION: It was discovered that gingerdione can inhibit intestinal motility, leading to the completion of this invention: a preventive and ameliorative agent for diarrhea or diarrhea-predominant irritable bowel syndrome, with gingerdione as an active ingredient.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an agent for preventing and improving diarrhea or diarrhea-predominant irritable bowel syndrome. [Background technology]

[0002] Irritable bowel syndrome (IBS) is a gastrointestinal disorder that causes abdominal pain and changes in bowel movements due to disturbances in colon motility caused by psychological stress or imbalance of the autonomic nervous system. IBS is characterized by the chronic or recurrent persistence of these symptoms, and is classified into constipation type, diarrhea type, alternating type, and unclassifiable type depending on the state of bowel movements. In diarrhea type, when colon motility is promoted, the water in the stool is not absorbed in the large intestine and is excreted as diarrhea.

[0003] It is said that there are 12 million patients in Japan (10-15% of the total population) who suffer from IBS symptoms, and the condition is particularly prevalent among young people in their teens and twenties. IBS is not a serious, life-threatening illness, but anxiety about stomach discomfort and diarrhea while out and about can interfere with work and life. As a countermeasure to these IBS symptoms, there is a need for the development of foods and beverages that can be taken regularly and have preventive and improving effects.

[0004] As prior art, for example, it is known that an agent for improving bowel movement frequency and volume, which contains lactoferrin and killed Lactobacillus brevis bacteria as active ingredients (Patent Document 1), and a composition containing a lipophilic extract of ginger and an artichoke extract obtained by supercritical CO2 extraction are useful for the prevention and treatment of irritable bowel syndrome (Patent Document 2).

[0005] It is known that raw ginger contains a lot of gingerol but almost no gingerdiol, but Patent Document 3 describes that a gingerdiol-containing lactic acid bacteria fermentation product can be obtained by fermenting a fermentation raw material containing gingerol with lactic acid bacteria. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent No. 5828349 [Patent Document 2] Patent No. 5769634 [Patent Document 3] Patent Publication No. 2022-95539 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention relates to diarrhea or diarrhea-predominant irritable bowel syndrome, and provides an agent for preventing or improving the same. [Means for solving the problem]

[0008] The inventors have found that gingerdiol can suppress intestinal motility, and have completed the present invention as a preventive and ameliorative agent for diarrhea or diarrhea-predominant irritable bowel syndrome, which contains gingerdiol as an active ingredient.

[0009] That is, the present invention relates to the following aspects [1] to [4]. [1] An agent for preventing and improving diarrhea or diarrhea-predominant irritable bowel syndrome, containing gingerdiol as an active ingredient. [2] An intestinal motility inhibitor whose active ingredient is gingerdiol. [3] A food, drink, medicine, quasi-drug, or feed containing the agent for preventing and improving diarrhea or diarrhea-predominant irritable bowel syndrome described in [1]. [4] A food, drink, medicine, quasi-drug, or feed containing the intestinal motility inhibitor described in [2]. Effect of the Invention

[0010] The present invention can provide a novel preventive and ameliorative agent that inhibits intestinal motility when ingested, and prevents and ameliorate diarrhea or diarrhea-predominant irritable bowel syndrome. [Brief description of the drawings]

[0011] [Figure 1]Regarding the inhibitory effect on colonic motility, the time required for expulsion of beads inserted into the large intestine after ingestion of corn oil, 6-shogaol, 6-gingerol, 6-paradol, 3R,5S-6-gingerdiol, or 3S,5S-6-gingerdiol is shown. [Diagram 2] As regards the inhibitory effect on small intestinal motility, the mobility in the small intestine of orally administered charcoal meal after ingestion of corn oil, 6-shogaol, 6-gingerol, 6-paradol, 3R,5S-6-gingerdiol or 3S,5S-6-gingerdiol is shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The intestinal motility inhibitor or agent for preventing and improving diarrhea or diarrhea-type irritable bowel syndrome of the present invention (hereinafter, sometimes collectively referred to as the preparation of the present invention) contains gingerdiol as an active ingredient and can exert an effect of inhibiting intestinal motility, such as inhibiting large intestinal motility and small intestinal motility, and is effective in preventing and improving diarrhea or diarrhea-type irritable bowel syndrome.

[0013] In the present invention, the gingerdiol serving as an active ingredient is not particularly limited as long as it can exert the above-mentioned effect, and a gingerdiol-containing substance can be used, preferably a purified product isolated and purified from a gingerdiol-containing substance, more preferably 6-gingerdiol, and even more preferably 3S,5S-6-gingerdiol.

[0014] Gingerdiol-containing substances can be obtained, for example, by fermenting a fermentation raw material containing gingerol using lactic acid bacteria. Examples of such microorganisms include those belonging to the genus Lactobacillus that have the ability to reduce aromatic carbonyl compounds to aromatic alcohol compounds. Heterofermentative lactic acid bacteria are preferred, and Lactobacillus fermentum (L. fermentum) or Lactobacillus reuteri (L. reuteri) are more preferred, and one or more types can be used.

[0015] The fermentation raw material is not particularly limited as long as it is a component that can be fermented by a bacterium capable of producing gingerdiol, and general medium components can be used, but examples include those containing a carbon source, a nitrogen source, inorganic substances, micronutrients, etc., and either a synthetic medium or a natural medium can be used. As the carbon source, glucose, sucrose, lactose, trehalose, glycerin, sorbitol, molasses, etc. can be used. As the nitrogen source, inorganic salts such as ammonium chloride, ammonium nitrate, ammonium sulfate, ammonium citrate, ammonium phosphate, etc., amino acids such as DL-alanine and L-glutamic acid, peptone, meat extract, yeast extract, malt extract, corn steep liquor, milk protein, soy protein, etc., which contain nitrogen, can be used. As the inorganic substance, calcium, sodium, potassium, magnesium, manganese, iron, zinc, etc. can be used. Furthermore, surfactants such as Tween 80, emulsifiers such as polyglycerol fatty acid esters, and fats and oils such as olive oil may be used. The use of calcium carbonate is preferable in that the production rate of gingerdiol increases.

[0016] The gingerol-containing substance may be either a natural product or a synthetic product, and is preferably a plant extract obtained by extracting a plant of the Zingiberaceae family, such as ginger or Guinea ginger. Examples of the method for extracting the plant extract include supercritical extraction, steam distillation, and solvent extraction. As long as gingerdiol is produced by fermentation using the above-mentioned bacteria, the gingerol content per solid content in the fermentation raw material is not particularly limited, and is preferably 0.1% by weight or more, more preferably 0.2 to 50% by weight, even more preferably 0.4 to 40% by weight, and particularly preferably 0.6 to 30% by weight. The gingerol-containing substance may be added during fermentation.

[0017] The gingerol-containing material is preferably emulsified so that it is well dispersed in the fermentation raw material, and may be made into an emulsified powder. The emulsifier is not particularly limited as long as it is a component having emulsifying ability, and examples thereof include gums such as acacia gum, ghatti gum, and xanthan gum, starch sodium octenyl succinate, casein, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, lecithin, and enzyme-treated lecithin, and one or more of them may be used. The emulsification treatment can be performed by a general emulsification method, and in detail, it can be performed using an emulsification device, and examples of the device include a high-pressure homogenizer, a colloid mill, an ultrasonic emulsifier, a homomixer, and a homodisper, and two or more types of devices may be combined.

[0018] As for the fermentation conditions, the liquid medium containing the fermentation raw material is sterilized, and then inoculated with lactic acid bacteria, and fermented by standing or shaking, but it is preferable to ferment under aerobic conditions by aeration, shaking, stirring, etc., the fermentation temperature can be, for example, 10 to 50°C, and preferably 15 to 40°C, the fermentation time can be, for example, 1 to 120 hours, preferably 2 to 96 hours, and more preferably 6 to 72 hours, and the pH can be, for example, 2.0 to 8.0, and preferably 3.0 to 7.5, and the pH may be adjusted within the above range during culture. Sodium hydroxide, ammonia, etc. can be used for pH adjustment, but it is preferable to use a calcium compound such as calcium carbonate, because it gradually dissolves as the culture solution becomes acidic during culture, mitigating the decrease in pH, making it possible to adjust the pH, and suppressing the inhibition of lactic acid bacteria growth associated with the decrease in pH.

[0019] The fermented product may be sterilized after fermentation. The sterilization conditions are not particularly limited as long as they are a general method, but for example, heating at 60 to 120°C for 1 to 30 minutes or at 80 to 100°C for 5 to 20 minutes is preferred. The fermented product may be recovered and used as a liquid obtained by solid-liquid separation by filtration using nonwoven fabric, mesh, etc., centrifugation, etc., and gingerdiol in the fermented product may be further purified by a general organic compound purification method such as solvent precipitation, distillation, reverse phase silica gel chromatography using ODS, column chromatography using ion exchange resin, etc. Furthermore, it may be concentrated and / or dried and used as a concentrated product or a dried product. Drying can be performed by drum drying, air drying, spray drying, vacuum drying, and / or freeze drying, etc.

[0020] As a method for taking the preparation of the present invention, the preparation containing gingerdiol may be administered orally or parenterally, but oral administration is preferred from the viewpoint of ease of continuous intake. There are no particular limitations on the intake amount or dosage as long as it has an intestinal motility inhibitory effect such as inhibition of large intestinal motility and inhibition of small intestinal motility, a preventive and ameliorative effect of diarrhea, or a preventive and ameliorative effect of diarrhea-predominant irritable bowel syndrome. Gingerdiol is preferably administered to humans at 2.5 mg / kg body weight or more per day, more preferably 3.0 to 100 mg / kg body weight, even more preferably 5.0 to 80 mg / kg body weight, and particularly preferably 7.5 to 50 mg / kg body weight. The preparation containing gingerdiol may be taken once a day or in several divided doses so that such an amount can be taken.

[0021] The preparation of the present invention can be added to various products to produce foods, beverages, medicines, quasi-drugs, feeds, etc., containing an intestinal motility inhibitor such as a large intestinal motility inhibitor or a small intestinal motility inhibitor, or an agent for preventing and improving diarrhea or diarrhea-type irritable bowel syndrome. This makes it possible to prepare foods, beverages, medicines, quasi-drugs, feeds, etc., having an intestinal motility inhibitory effect such as inhibition of large intestinal motility or inhibition of small intestinal motility, or an effect of preventing and improving diarrhea or diarrhea-type irritable bowel syndrome. The amount of the preparation added to each food, beverage, etc. is not particularly limited, but is preferably 0.001 to 50% by weight, more preferably 0.01 to 30% by weight, even more preferably 0.05 to 20% by weight, and particularly preferably 0.1 to 10% by weight. The foods, beverages, etc. to which the preparation is added are not particularly limited, but can be used for various foods, beverages, such as beverages, foods, seasonings, functional foods, and supplements, as well as medicines, quasi-drugs, feeds, etc. EXAMPLES

[0022] The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following examples. In the present invention, all % is by weight unless otherwise specified.

[0023] [Example 1] (Purification of 6-gingerdiol) Ginger extract powder G2 (6-gingerol content: 2.3%, Ikeda Tohka Kogyo Co., Ltd.) was added to the MRS medium as a gingerol-containing substance to a final concentration of 5%, and 20 g of the mixture was dispensed into test tubes and heat-sterilized at 121°C for 15 minutes. A loopful of Lactobacillus fermentum NBRC15885 or Lactobacillus brevis NBRC3345 was inoculated into two cooled liquid media, and cultured statically at 30°C for 40 hours. After the culture was completed, the mixture was sterilized at 90°C for 10 minutes to obtain each lactic acid bacteria fermentation product. Each lactic acid bacteria fermentation product was purified by the purification method described below, and a purified 3S,5S-6-gingerdiol product was prepared from the L. fermentum NBRC15885 fermentation product, and a purified 3R,5S-6-gingerdiol product was prepared from the L. brevis NBRC3345 fermentation product, and used in the following tests.

[0024] <Purification method> (1) Add ethyl acetate and NaCl to the lactic acid bacteria fermentation product, mix, and centrifuge. (2) The ethyl acetate layer is collected, concentrated, dissolved in acetonitrile, and used for purification. (3) (2) is added to a C18 resin column, and an appropriately-set concentration of acetonitrile aqueous solution is passed through to separate the components in (2). (4) During the period of (3), samples are taken at regular intervals and separated, then analyzed by HPLC, and samples in which the target components are detected are selected. (5) The selected sample is concentrated and recovered with diethyl ether, after which the diethyl ether is evaporated to produce a purified product.

[0025] (Inhibitory effect on colon motility) Male C57bL / 6N mice (9-12 weeks old) were fasted for 24 hours, and on the day of the test, corn oil, or 6-shogaol, 6-gingerol, 6-paradol, 3R,5S-6-gingerdiol, or 3S,5S-6-gingerdiol dissolved in corn oil was orally administered at 100 mg / kg (n=6). Thirty minutes after administration, colonic beads were inserted from the anus and the time until excretion was measured. The excretion time of the beads for each sample administration was calculated and shown in Figure 1.

[0026] As shown in Figure 1, the time to expel beads was significantly (p<0.05) longer in mice orally administered 3S,5S-6-gingerdiol than in mice orally administered corn oil, and it was confirmed that the time to expel beads also tended to increase in mice orally administered 6-shogaol and 3R,5S-6-gingerdiol. Therefore, it was found that the large intestine motility was suppressed in mice orally administered 6-gingerdiol.

[0027] [Example 2] (Small intestinal motility suppression effect) Male C57bL / 6N mice (9-12 weeks old) were fasted for 24 hours, and on the day of the test, corn oil, or 6-shogaol, 6-gingerol, 6-paradol, 3R,5S-6-gingerdiol, or 3S,5S-6-gingerdiol dissolved in corn oil was orally administered at 100 mg / kg (n=6). Thirty minutes after administration, 0.2 ml of charcoal meal was orally administered, and one hour later, the mice were autopsied and the small intestine was removed. The total length (A) and the length of progression of the charcoal meal (B) for each sample were measured, and the average mobility of the charcoal meal (B / A×100(%)) was calculated and shown in Figure 2. Note that the higher the mobility in the intestine, the more active the intestinal peristalsis.

[0028] Compared to mice orally administered corn oil, mice orally administered 3S,5S-6-gingerdiol showed a significant (p<0.05) decrease in charcoal meal mobility, and a tendency for 6-shogaol to also decrease the mobility of charcoal meal was confirmed. Thus, it was found that small intestinal motility was significantly (p<0.05) suppressed in mice orally administered 3S,5S-6-gingerdiol.

[0029] From the above, it was found that oral administration of gingerdiol can suppress intestinal motility and that gingerdiol can be used as an inhibitor of intestinal motility, making it useful for preventing and improving diarrhea and diarrhea-predominant irritable bowel syndrome.

Claims

1. An agent for preventing and improving diarrhea or diarrhea-predominant irritable bowel syndrome, comprising gingerdiol as an active ingredient.

2. An intestinal motility inhibitor whose active ingredient is gingerdiol.

3. A food, drink, medicine, quasi-drug, or feed comprising the agent for preventing and improving diarrhea or diarrhea-predominant irritable bowel syndrome according to claim 1.

4. A food, drink, medicine, quasi-drug or feed comprising the intestinal motility inhibitor according to claim 2.

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