Joint movement improvement or joint pain alleviation agent, food and drink or feed for joint movement improvement or joint pain alleviation, and pharmaceutical composition for joint movement improvement or joint pain alleviation

Abstract

To provide a joint movement improvement or joint pain alleviation agent, a food and drink or a feed for joint movement improvement or joint pain alleviation, and a pharmaceutical composition for joint movement improvement or joint pain alleviation which have high safety and are excellent in a joint movement improvement effect or a joint pain alleviation effect.SOLUTION: A joint movement improvement or joint pain alleviation agent includes a bacterial body and / or a culture of Bacillus subtilis.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for improving joint movement or relieving joint pain, a food, drink, or feed for improving joint movement or relieving joint pain, and a pharmaceutical composition for improving joint movement or relieving joint pain. [Background technology]

[0002] In Japan, the proportion of elderly people is increasing year by year. For this reason, it is important to improve the quality of life of the elderly. One of the symptoms associated with aging is osteoarthritis of the knee. This condition is caused by wear of the cartilage that cushions the knee joint and weakened muscle strength, which leads to inflammation of the knee joint and deformation of the joint, resulting in pain. The estimated number of patients with osteoarthritis of the knee is said to be as high as 24 million people over the age of 50, and joint diseases are also a major cause of the need for support and nursing care, so more proactive measures are needed.

[0003] To date, glucosamine, Acanthus persica extract, salmon nasal cartilage-derived proteoglycan, non-denatured type II collagen, collagen peptides, and other ingredients have been reported to have the effect of promoting the repair of damaged cartilage in osteoarthritis of the knee.

[0004] It has been reported that Bacillus subtilis has various actions and can be used as an active ingredient of various agents. For example, agents for increasing intestinal butyric acid-producing bacteria (see, for example, Patent Document 1), agents for suppressing the increase and / or decrease of bifidobacteria in the large intestine (see, for example, Patent Document 2), agents for preventing norovirus infection (see, for example, Patent Document 3), agents for improving functional gastrointestinal disorders (see, for example, Patent Document 4), agents for improving bone metabolism or bone density (see, for example, Patent Document 5), agents for preventing and treating inflammatory bowel disease (see, for example, Patent Document 6), agents for improving lipid metabolism (see, for example, Patent Document 7), and agents for improving renal function (see, for example, Patent Document 8) have been reported. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2013-147469 A [Patent Document 2] International Publication No. 2011 / 111783 [Patent Document 3] JP 2016-121086 A [Patent Document 4] JP 2017-109973 A [Patent Document 5] JP 2017-226649 A [Patent Document 6] International Publication No. 2008 / 069102 [Patent Document 7] International Publication No. 2008 / 023608 [Patent Document 8] International Publication No. 2008 / 023607 Summary of the Invention [Problem to be solved by the invention]

[0006] As described above, although ingredients useful for knee osteoarthritis have been reported, there remains a strong demand for new materials that are highly safe and can improve the movement of joints, including the knee, and relieve joint pain, and there is currently a strong demand for such materials to be provided as soon as possible.

[0007] The present invention aims to solve the above-mentioned problems in the prior art and to achieve the following object: That is, the present invention aims to provide an agent for improving joint movement or relieving joint pain, a food, drink, or feed for improving joint movement or relieving joint pain, and a pharmaceutical composition for improving joint movement or relieving joint pain, which are highly safe and have an excellent effect of improving joint movement or relieving joint pain. [Means for solving the problem]

[0008] In order to solve the above problems, the present inventors conducted extensive research and found that orally ingesting highly safe Bacillus subtilis cells and / or a culture thereof significantly improves joint movement and significantly relieves joint pain.

[0009] The present invention is based on the findings of the present inventors, and the means for solving the above problems are as follows. <1> An agent for improving joint movement or relieving joint pain, comprising Bacillus subtilis cells and / or a culture. <2> The culture is a soybean culture. <1> The present invention relates to an agent for improving joint movement or relieving joint pain, which is described in the above. <3> The above containing Bacillus subtilis spores <1> or <2> The present invention relates to an agent for improving joint movement or relieving joint pain, which is described in the above. <4> The Bacillus subtilis is Bacillus subtilis C-3102 strain (FERM BP-1096). <1> from <3> The present invention relates to an agent for improving joint movement or relieving joint pain, comprising: <5> The above mentioned substances are taken orally. <1> from <4> The present invention relates to an agent for improving joint movement or relieving joint pain, comprising: <6> 2.0 x 10 per day 8 ~2.5×10 11 The Bacillus subtilis is formulated to be administered at CFU <1> from <5> The present invention relates to an agent for improving joint movement or relieving joint pain, comprising: <7> 2.0 x 10 per day 9 ~2.0×10 10 The Bacillus subtilis is formulated to be administered at CFU <1> from <6> The present invention relates to an agent for improving joint movement or relieving joint pain, comprising: <8> A food, drink, or feed for improving joint movement or relieving joint pain, characterized by containing Bacillus subtilis cells and / or a culture. <9> A pharmaceutical composition for improving joint movement or relieving joint pain, comprising Bacillus subtilis cells and / or a culture. Effect of the Invention

[0010] According to the present invention, it is possible to solve the above-mentioned conventional problems and achieve the above-mentioned object, and to provide an agent for improving joint movement or relieving joint pain, a food, drink, or feed for improving joint movement or relieving joint pain, which is highly safe and has an excellent effect of improving joint movement or relieving joint pain, and a pharmaceutical composition for improving joint movement or relieving joint pain. [Brief description of the drawings]

[0011] [Figure 1] Fig. 1 is a graph showing the test results of Test Example 1. In Fig. 1, "*" indicates "p<0.05." [Diagram 2] Figure 2 is a graph showing the change over time in the "JKOM score" in the test of Test Example 2. In Figure 2, "*" indicates "p<0.05." [Diagram 3] Figure 3 is a graph showing the change over time in the "daily life status score" in the test of Test Example 2. In Figure 2, "*" indicates "p<0.05." DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] (Improves joint movement or relieves joint pain) The agent for improving joint movement or relieving joint pain of the present invention contains at least Bacillus subtilis cells and / or a culture thereof as an active ingredient, and further contains other ingredients as necessary.

[0013] <Bacillus subtilis cells and / or cultures> Bacillus subtilis has been deeply involved in human life for a long time, such as in the production of enzymes and food, and there is a lot of information about its functionality, but it is not known that it is useful for improving joint movement or relieving joint pain. Bacillus subtilis is an obligately aerobic gram-positive bacterium that forms spores, which are resistant to high temperatures and digestive enzymes. One embodiment of the agent for improving joint movement or relieving joint pain of the present invention contains this Bacillus subtilis in a spore state, and therefore, even if taken orally, it can reach the intestine alive and exert its effect.

[0014] The mycological properties of Bacillus subtilis are described in, for example, Burgess Manual of Bacteriology Vol. 11 (1986), and specifically, it has the following characteristics: (1) Gram-positive (2) Formation of oval spores (3) Bacillus (4) Motility: Yes (5)Aerobic (6) Catalase: Positive (7) Growth at 50℃:+ (8) Growth at pH 5.7: + (9) Citrate Utilization:+ (10) Acid production from sugars: Arabinose, glucose, xylose, mannitol: + (11) VP reaction: + (12) Starch hydrolysis:+ (13) Nitrate reduction: + (14) Formation of indole:- (15) Hydrolysis of gelatin:+ (16)Casein hydrolysis:+ (17) Coating formation in liquid medium:+ (18) Coagulation of milk:- (19) Peptonization of milk:+

[0015] The Bacillus subtilis used in the present invention is not particularly limited and may be appropriately selected depending on the purpose. A preferred example is Bacillus subtilis C-3102 strain (deposited on December 25, 1985 at the Fermentation Research Institute, Agency of Industrial Science and Technology, Ministry of International Trade and Industry under the accession number FERM BP-1096 (currently the Patent Organism Depositary Center, National Institute of Technology and Evaluation: Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture)).

[0016] Bacillus subtilis C-3102 strain is known to have various useful effects, such as regulating the intestines (WO 2011 / 111783), improving lipid metabolism (WO 2008 / 23608), and improving renal function (WO 2008 / 023607). Food products containing Bacillus subtilis C-3102 strain are already on the market, and its safety when taken over a long period of time has been established.

[0017] Soybean cultures of Bacillus subtilis C-3102 strain have effects on birds and livestock, such as improving the intestinal flora, promoting body weight, preventing infection, strengthening eggshells, improving meat quality, and reducing fecal odor, and are used as feed additives (JP Patent Publication No. 4-24022) and as an eggshell strength enhancer for birds (JP Patent Publication No. 10-108628). This strain is also known to have health benefits, such as regulating the intestines and reducing putrefactive products in the intestines (Journal of the Society of Intestinal Microbiology, Vol. 18, No. 2, pp. 93-99 (2004)).

[0018] Bacillus subtilis C-3102 strain is characterized in that a fragment of about 700 bps is amplified when PCR is performed using the PCR primers of the following sequence 1 and sequence 2. There is no other Bacillus subtilis in which amplification occurs with both of these PCR primers. The fragment of about 700 bps amplified using the genome of Bacillus subtilis C-3102 strain as a template is characterized in that it does not have homology to the amylase sequence, and in this respect, the C-3102 strain is clearly distinguished from other strains of Bacillus subtilis. Sequence 1 (forward primer): 5'-GCCCCGCACATACGAAAAGACTGGCTGAAA-3' (SEQ ID NO: 1) Sequence 2 (reverse primer): 5'-GGATCCCACGTTGTGATTAAAAGCAGCGAT-3' (SEQ ID NO: 2)

[0019] In addition, Bacillus subtilis strain C-3102 has the following properties: (1) It does not contain plasmid DNA. (2) Genomic DNA was prepared, digested with the restriction enzyme NotI or SfiI, and separated by agarose electrophoresis; the digestion pattern was as previously reported (Figure 1 in WO 2008 / 023607 and Figure 1 in WO 2008 / 023608). (3) No resistance to ampicillin, chloramphenicol, ciprofloxacin, erythromycin, gentamicin, kanamycin, linezolid, quinupristin / dalfopristin, rifampin, streptomycin, tetracycline, trimethoprim, or vancomycin (minimum inhibitory concentrations for all are 0.03 to 4 μg / ml).

[0020] Bacillus subtilis can be cultured using a liquid or solid medium containing a carbon source, a nitrogen source, inorganic substances, etc. that are usually used in microbial culture. The carbon source may be any carbon source that can be assimilated by Bacillus subtilis, such as glucose, fructose, sucrose, starch, molasses, etc., and the nitrogen source may be, for example, peptone, casein hydrolysate, meat extract, ammonium sulfate, etc. Furthermore, salts such as phosphate, potassium, magnesium, calcium, sodium, iron, and manganese, vitamins, amino acids, surfactants, etc. may be added as necessary. In addition to these synthetic media, natural substances such as soybean meal may be used for the culture. The culture conditions are preferably aerobic conditions, and the culture apparatus is preferably aerated and agitated liquid culture using a jar fermenter, for example. The culture temperature is preferably 20 to 50°C, particularly 30 to 45°C, the culture time is 12 hours to 7 days, and the initial culture pH is pH 5 to 9, particularly preferably pH 6 to 8.

[0021] The culture thus obtained contains the bacteria of Bacillus subtilis, a medium and a fermentation product. The culture may be used as it is as an agent for improving joint movement or relieving joint pain, or the culture may be concentrated, or may be used as a formulation such as a dry powder, granules or tablets by adding an excipient or the like. The bacteria separated from the culture may be used (e.g., spores), or the culture may be used after removing the bacteria from the culture (e.g., culture supernatant), or the culture may be used in a form containing the bacteria. In one embodiment, Bacillus subtilis is cultured using natural products suitable for food, such as soybean oil cake, boiled soybeans, boiled red beans, cooked rice, barley and rice, wheat bran, boiled corn, and other grains, and the culture is blended directly into food, drink, feed, etc. without separating the bacteria from the culture. In another embodiment, the culture supernatant of Bacillus subtilis is separated and blended into food, medicine, etc. In yet another embodiment, Bacillus subtilis cells (spores) are added to foods, medicines, etc.

[0022] Among the above cultures, soybean cultures cultured using soybean-derived substances are preferred. Examples of soybean-derived substances include soybean oil cake and boiled soybeans, with soybean oil cake being particularly preferred.

[0023] The Bacillus subtilis may be any of a spore, a mixture of a spore and a germinant, or a germinant, but the agent for improving joint movement or relieving joint pain preferably contains a Bacillus subtilis spore.

[0024] <Other ingredients> Other ingredients in the agent for improving joint movement or relieving joint pain are not particularly limited and can be appropriately selected depending on the purpose, so long as they do not impair the effects of the present invention. Examples of such ingredients include ingredients that can be used when formulating the agent into a formulation, as described below. The other components may be used alone or in combination of two or more. The content of the other ingredients in the agent for improving joint movement or relieving joint pain is not particularly limited and can be appropriately selected depending on the purpose.

[0025] The agent for improving joint movement or relieving joint pain of the present invention safely and simply improves joint movement or relieves joint pain. The agent for improving joint movement or relieving joint pain is preferably one that is taken orally. The agent for improving joint movement or relieving joint pain of the present invention can particularly improve knee joint movement or relieve knee joint pain, and therefore has the function of supporting knee joint movement and relieving pain and discomfort in the knee joint.

[0026] The agent for improving joint movement or relieving joint pain of the present invention may be appropriately formulated together with pharmacologically acceptable carriers and additives and administered in the form of a liquid, powder, granules, capsules, tablets, etc., or may be added to food, beverages, or feed.

[0027] When the agent for improving joint movement or relieving joint pain of the present invention is formulated as a tablet, examples of pharmacologically acceptable carriers used include excipients, lubricants, binders, disintegrants, preservatives, antioxidants, colorants, flavoring agents, etc., but are not limited to these, and other commonly used carriers can be used as appropriate.

[0028] Examples of excipients include lactose, sucrose, D-mannitol, D-sorbitol, starch, pregelatinized starch, dextrin, crystalline cellulose, low-substituted hydroxypropylcellulose, sodium carboxymethylcellulose, gum arabic, pullulan, light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate.

[0029] Examples of lubricants include sugar esters such as sucrose fatty acid esters and glycerin fatty acid esters, calcium stearate, magnesium stearate, stearic acid, stearyl alcohol, hydrogenated oils such as powdered vegetable oils and fats, waxes such as white beeswax, talc, silicic acid, and silicon.

[0030] Examples of binders include pregelatinized starch, sucrose, gelatin, gum arabic, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, sucrose, D-mannitol, trehalose, dextrin, pullulan, hydroxypropylcellulose, hydroxypropylmethylcellulose, and polyvinylpyrrolidone.

[0031] Examples of disintegrants include lactose, sucrose, starch, carboxymethylcellulose, calcium carboxymethylcellulose, croscarmellose sodium, sodium carboxymethylstarch, light anhydrous silicic acid, and low-substituted hydroxypropylcellulose.

[0032] Examples of preservatives include paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, and sorbic acid, while examples of antioxidants include sulfites and ascorbates.

[0033] Examples of coloring agents include water-soluble edible tar dyes, water-insoluble lake dyes, and natural dyes such as β-carotene, chlorophyll, and red iron oxide.

[0034] Examples of sweeteners include sodium saccharin, dipotassium glycyrrhizinate, aspartame, and stevia.

[0035] In addition to the above, the composition may contain, for example, vitamins, minerals, amino acids, tea extracts such as catechin and sweet tea, glucosamine, chondroitin, plant extracts such as saw palmetto and apple, polyphenols contained in grapes and apples, lactic acid bacteria, bifidobacteria, butyric acid bacteria, natto bacteria, saccharifying bacteria, yeast, starch, dextrin, gum arabic, sugar alcohols such as mannitol and xylitol, cellulose derivatives such as crystalline cellulose and hydroxypropyl cellulose, gelatin, glycerin, fermented milk, lactoferrin, dietary fiber, flavors, etc.

[0036] In particular, tablets containing the agent for improving joint movement or relieving joint pain of the present invention preferably contain monosaccharides such as glucose and fructose, disaccharides such as sucrose and lactose, oligosaccharides such as isomalt and cyclodextrin, sugars such as granulated sugar, maltose, and lactose, and starch, and more preferably contain maltose and starch.

[0037] The tablets may be sugar-coated, coated, or plain. Sugar-coated and coated tablets generally have lower disintegration properties than plain tablets, but have the advantage that the flavor and odor of the active ingredient are less noticeable. The shape, structure and size of the tablet are not particularly limited and can be appropriately selected depending on the purpose.

[0038] The amount of the agent for improving joint movement or relieving joint pain of the present invention to be ingested is not particularly limited and can be appropriately selected depending on the purpose. 8 ~2.5×10 11 The formulation is preferably formulated to provide a CFU of Bacillus subtilis of 2.0 x 10 9 ~2.0×10 10 More preferably, the formulation is such that CFU of Bacillus subtilis can be administered.

[0039] The number of times of administration of the agent for improving joint movement or relieving joint pain of the present invention is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 1 to 5 times a day, more preferably 1 to 4 times a day, and particularly preferably 1 to 3 times a day or once a day. The agent for improving joint movement or relieving joint pain of the present invention is desirably formulated as a tablet suitable for administration as described above.

[0040] For example, the amount of Bacillus subtilis per tablet is not particularly limited and can be selected appropriately depending on the purpose. 7 ~2.5×10 11 CFU is preferred, 2.0 x 10 8 ~9.0×1010 CFU is more preferred, 4.0 × 10 8 ~4.0×10 10 More preferably, 4.0 x 10 CFU 8 ~2.0×10 10 CFU is particularly preferred.

[0041] The number of tablets to be taken at one time is not particularly limited and can be appropriately selected depending on the purpose, and examples include 1 to 5 tablets.

[0042] There are no particular limitations on the target subjects of the agent for improving joint movement or relieving joint pain of the present invention, so long as they are people who need to take the agent, and the target subjects can be appropriately selected depending on the purpose, such as people who have joint pain or discomfort, and people who need support for joint movement due to aging.

[0043] Bacillus subtilis, which is an active ingredient of the agent for improving joint movement or relieving joint pain of the present invention, is effective in a small amount and for a short period of time, has excellent storage stability and acid resistance, and easily reaches the intestines and grows there, so that a sustained effect of improving joint movement or relieving joint pain can be expected. Meanwhile, Bacillus subtilis of the present invention can be safely ingested for a long period of time. Therefore, the agent for improving joint movement or relieving joint pain of the present invention is preferably used continuously for 4 weeks or more, preferably 8 weeks or more, and more preferably 12 weeks or more.

[0044] The agent for improving joint movement or relieving joint pain of the present invention can improve joint movement or relieve joint pain. Bacillus subtilis, the active ingredient, has been used in foods and the like for a long time and can be safely taken orally for a long period of time. Therefore, the agent for improving joint movement or relieving joint pain of the present invention is useful not only as a medicine, but also as a quasi-drug, food, drink, or feed for the purpose of improving joint movement or relieving joint pain.

[0045] (Food, drink, or feed for improving joint movement or relieving joint pain) The food, drink, or feed of the present invention for improving joint movement or relieving joint pain contains at least Bacillus subtilis cells and / or a culture as an active ingredient, and further contains other ingredients as necessary.

[0046] The Bacillus subtilis cells and / or culture are the same as the Bacillus subtilis cells and / or culture described in the above section of the present invention (Agent for improving joint movement or relieving joint pain).

[0047] The other ingredients in the food, drink, or feed for improving joint movement or relieving joint pain are not particularly limited and can be appropriately selected depending on the type of food, drink, or feed. The content of other ingredients in the food, drink, or feed for improving joint movement or relieving joint pain is not particularly limited and can be appropriately selected depending on the type of food, drink, or feed.

[0048] The type of food or drink is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include beverages, confectionery tablets, pastes, breads, processed fish products, dairy products, jellies, candies, retort foods, cookies, castella cakes, biscuits, chocolates, etc. Alternatively, the agent for improving joint movement or relieving joint pain of the present invention may be added to these various food materials. The food or drink of the present invention can be provided as a health drink, health food, or functional food.

[0049] The amount of Bacillus subtilis cells and / or cultures contained in food and beverages is determined appropriately depending on the type and purpose of the food and beverage. Taking into account the usual intake of food and beverages, 8 ~2.5×10 11 It is preferable that the formula is formulated so that the CFU of Bacillus subtilis can be ingested, and 2.0 x 10 9 ~2.0×10 10 It is preferable that the product be formulated to provide CFU of Bacillus subtilis.

[0050] The number of times of ingestion per day can be appropriately selected according to the type of food and drink and the purpose. For example, in the case of health foods and functional foods, it is preferable to take them once to five times a day, more preferably once to four times a day, and particularly preferably once to three times a day or once a day. The food and drink of the present invention can improve joint movement and relieve joint pain by continuously taking them.

[0051] The subject of the feed is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include birds such as chickens, mammals such as cows, pigs, sheep, goats, etc., fish, etc. The feed may be produced by adding the above-mentioned agent for improving joint movement or relieving joint pain of the present invention to an existing feed.

[0052] The amount of Bacillus subtilis cells and / or cultures contained in the feed is determined appropriately depending on the subject and purpose of the feed. For example, in the case of cows, it is 1 × 10 6 It is preferable to mix it so that the CFU / kg or more is 5 x 10 6 ~6×10 8 It is more preferable to mix the larvae so that the CFU / kg is reached. For example, in the case of birds, the daily dose is 1×10 3 ~1×10 11 It is preferable to mix it so that it is CFU / g, and 1×10 3 ~1×10 7 It is more preferable to mix it so that it is 1×10 CFU / g. 4 ~1×10 6 It is particularly preferable to formulate the compound so as to obtain CFU / g.

[0053] The feed may be appropriately mixed with vitamins, minerals, amino acids, flavorings, acidulants, baking soda, emulsifiers, stabilizers, etc., depending on the subject. By continuously feeding the feed of the present invention to livestock, etc., it is possible to improve joint movement and relieve joint pain.

[0054] As a method for producing the food, drink, or feed, a known method can be appropriately selected except for blending the bacterial cells and / or culture of Bacillus subtilis.

[0055] (Pharmaceutical composition for improving joint movement or relieving joint pain) The pharmaceutical composition of the present invention for improving joint movement or relieving joint pain contains at least Bacillus subtilis cells and / or a culture as an active ingredient, and further contains other ingredients as necessary.

[0056] The pharmaceutical composition of the present invention for improving joint movement or relieving joint pain can be used, for example, for the prevention or treatment of discomfort in joint movement, joint pain, and the like.

[0057] The Bacillus subtilis cells and / or culture are the same as the Bacillus subtilis cells and / or culture described in the above section of the present invention (Agent for improving joint movement or relieving joint pain).

[0058] The other ingredients in the pharmaceutical composition for improving joint movement or relieving joint pain are not particularly limited and can be appropriately selected depending on the type of pharmaceutical composition. The content of other ingredients in the pharmaceutical composition for improving joint movement or relieving joint pain is not particularly limited and can be appropriately selected depending on the type of pharmaceutical composition.

[0059] The route of administration of the pharmaceutical composition of the present invention for improving joint movement or relieving joint pain is not particularly limited and may be appropriately selected depending on the purpose. However, as described above, Bacillus subtilis cells or a culture thereof are effective in a small amount and for a short period of time, and safety is guaranteed when administered orally. They have excellent storage stability and acid resistance, and easily reach the intestines and grow there. They are expected to have a sustained effect of improving joint movement and relieving joint pain, so oral administration is simple and preferable.

[0060] When administered orally, the pharmaceutical composition for improving joint movement or relieving joint pain of the present invention is appropriately formulated with pharmacologically acceptable carriers and additives, and administered in the form of liquid, powder, granules, capsules, tablets, etc. Examples of pharmacologically acceptable carriers used include, but are not limited to, excipients, lubricants, binders, disintegrants, preservatives, antioxidants, colorants, flavoring agents, etc., and other commonly used carriers can also be used appropriately. Specific examples of the above carriers are the same as those described in the above section of the present invention (Agent for improving joint movement or relieving joint pain).

[0061] The dosage of the pharmaceutical composition of the present invention for improving joint movement or relieving joint pain is not particularly limited and can be appropriately selected depending on the purpose. 8 ~2.5×10 11 The preferred dose of Bacillus subtilis is 2.0 × 10 CFU. 9 ~2.0×10 10 A dose that allows for CFU of Bacillus subtilis is preferred.

[0062] The number of times the pharmaceutical composition of the present invention for improving joint movement or relieving joint pain is taken is not particularly limited and can be appropriately selected depending on the purpose, but it is preferably taken once to five times a day, more preferably once to four times a day, and particularly preferably taken in divided doses of once to three times a day or once a day.

[0063] For example, the amount of Bacillus subtilis per tablet is not particularly limited and can be selected appropriately depending on the purpose. 7 ~2.5×10 11 CFU is preferred, 2.0 x 10 8 ~9.0×10 10 CFU is more preferred, 4.0 × 10 8 ~4.0×10 10 More preferably, 4.0 x 10 CFU 8 ~2.0×10 10 CFU is particularly preferred.

[0064] The number of tablets to be taken at one time is not particularly limited and can be appropriately selected depending on the purpose, and examples include 1 to 5 tablets.

[0065] The duration of administration of the pharmaceutical composition of the present invention for improving joint movement or relieving joint pain is not particularly limited and may be appropriately selected depending on the purpose, but it is recommended to use it continuously for 4 weeks or more, preferably 8 weeks or more, and more preferably 12 weeks or more.

[0066] The agent for improving joint movement or relieving joint pain, food, beverage, or feed for improving joint movement or relieving joint pain, and pharmaceutical composition for improving joint movement or relieving joint pain of the present invention may be used in combination with other pharmaceuticals, food, beverage, or feed for improving joint movement or relieving joint pain.

[0067] The present invention also relates to a method for improving joint movement or relieving joint pain, which comprises administering the above-mentioned Bacillus subtilis cells and / or culture to a subject. EXAMPLES

[0068] The present invention will be specifically explained below by way of test examples, but the present invention is not limited to these test examples.

[0069] In the following, as an example of Bacillus subtilis, Bacillus subtilis C-3102 strain (deposited on December 25, 1985 at the Fermentation Research Institute, Agency of Industrial Science and Technology, Ministry of International Trade and Industry under the accession number FERM BP-1096 (currently the Patent Organism Depositary Center, National Institute of Technology and Evaluation: Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture)) was used.

[0070] (Test Example 1: Human test on healthy middle-aged and elderly people) <Preparation of tablets> 5 kg of water was added to 10 kg of commercially available soybean meal granules, sterilized at 121°C for 60 minutes, inoculated with a culture solution of Bacillus subtilis C-3102 strain (accession number FERM BP-1096) that had been pre-cultured, and cultured at about 37°C for 60.5 hours to produce a soybean culture of Bacillus subtilis C-3102 strain. The resulting culture was dried and crushed (hereinafter sometimes referred to as "fermented soybean powder") and mixed with other ingredients shown in the "Composition of sugar-coated tablets" below to produce sugar-coated tablets. The "Nutritional information of sugar-coated tablets" is also shown below.

[0071] - Composition of sugar-coated tablets - Sugar 70% by mass Fermented soybean powder: 9% by mass Starch: 7% by mass Lubricant: 0.9% by mass Others: 13.1% by mass Total 100% by mass * Fermented soybean powder is made by mixing Bacillus subtilis C-3102 strain for 10 10 The Bacillus subtilis C-3102 strain is contained in the spore state.

[0072] -Nutritional information for sugar-coated tablets (Nutritional analysis value per 3 tablets (1.14g))- Energy: 4.02kcal Protein: 0.08g Fat: 0.01-0.03g Carbohydrates: 0.88g Salt equivalent: 0~0.00001g

[0073] <Test methods and results> A double-blind, randomized, placebo-controlled, parallel-group comparative study was conducted to investigate the effect of Bacillus subtilis C-3102 strain on joint pain. The subjects in this study were 100 healthy middle-aged and elderly people (age: 50-79 years). In this study, healthy subjects were those excluding those who had or had a history of serious diseases such as diabetes, brain disease, circulatory system disease, liver disease, kidney disease, and heart disease. The subjects were randomly divided into a Bacillus subtilis C-3102 strain intake group and a placebo intake group.

[0074] The test food group that received Bacillus subtilis C-3102 strain was given 4.6 × 10 9 The subjects were asked to take three sugar-coated tablets containing CFU of Bacillus subtilis C-3102 strain per day for four weeks, while the placebo group was asked to take three placebo tablets containing dextrin instead of fermented soybean powder per day.

[0075] The subjects were asked to fill out a questionnaire about joint pain using the following five-point scale before and after the start of the study. The average change in the scores of the questionnaire before and after the start of the study (after the start of the study - before the start of the study) is calculated and the results are shown in Figure 1. 1 point: Not a problem at all. 2 points: I'm a bit worried. 3 points: I'm in trouble. 4 points: Very troubled. 5 points: The problem is unbearable.

[0076] As shown in Figure 1, the Bacillus subtilis C-3102 strain intake group (mean change: -0.2) showed a significant improvement in score compared to the placebo intake group (mean change: 0.2).

[0077] (Test Example 2: Human test on healthy adults) <Preparation of tablets> Fermented soybean powder was produced in the same manner as in Test Example 1. The fermented soybean powder was mixed with other ingredients shown in the "Composition of Coated Tablets" below to produce coated tablets. The "Nutritional Information of Coated Tablets" is also shown below.

[0078] -Composition of coated tablets- Sugar 71.3% by mass Fermented soybean powder: 16.2% by mass Starch: 3.3% by mass Lubricant: 1.9% by mass Others: 7.3% by mass Total 100% by mass * Fermented soybean powder is made by mixing Bacillus subtilis C-3102 strain for 10 10 The Bacillus subtilis C-3102 strain is contained in the spore state.

[0079] -Nutritional information for coated tablets (Nutritional analysis value per 3 tablets (0.615g))- Energy: 2.41kcal Protein: 0.07g Fat: 0.01-0.03g Carbohydrates: 0.49g Salt equivalent: 0~0.00001g

[0080] <Test methods and results> A double-blind, randomized, placebo-controlled, parallel-group comparative study was conducted to investigate the effect of Bacillus subtilis C-3102 strain on joint pain. Eighty-eight healthy adults (ages: 20-69 years) were subjects in this study. In this study, healthy subjects were those diagnosed with a Kellgren-Lawrence classification (KL grade) of 0 or 1 in a knee X-ray examination. The subjects were randomly divided into a Bacillus subtilis C-3102 intake group and a placebo intake group so that the JKOM score and KL grade based on the Japanese Knee Osteoarthritis Measure (JKOM) were uniform.

[0081] The test food group taking Bacillus subtilis C-3102 strain was given 3.4 × 10 9The subjects were instructed to take three coated tablets containing CFU of Bacillus subtilis C-3102 strain per day, while the placebo group was instructed to take three placebo tablets containing dextrin instead of fermented soybean powder per day for 12 weeks.

[0082] Subjects were evaluated using the JKOM before the start of the study (week 0), and then four weeks (week 4), eight weeks (week 8), and 12 weeks (week 12) after the start of the study.

[0083] In addition to the degree of knee pain felt by the patient, the JKOM is made up of 25 questions about knee pain and related movements. The condition of knee pain can be understood from the subscores made up of 25 questions such as "knee pain and stiffness," "daily life status," "regular activities," and "health status," and the "JKOM score" calculated from these subscores. The higher the score, the greater the degree of knee pain.

[0084] Figure 2 shows the trends in the "JKOM score" (average value) for each group, and Figure 3 shows the trends in the "daily life status score" (average value).

[0085] As shown in Figures 2 and 3, the overall score "JKOM score" (Figure 2) and the subscale "Daily Life Status Score" (Figure 3) were significantly improved in the Bacillus subtilis C-3102 strain intake group compared to the placebo intake group.

[0086] (Formulation Example 1: Capsules) A soybean culture of Bacillus subtilis C-3102 strain was mixed with edible oil and fat, and the mixture was filled into a soft capsule shell consisting of the following ingredients in a conventional manner to obtain soft capsules weighing 380 mg each. <Contents> Bacillus subtilis C-3102 strain soybean culture 100mg · Edible fats and oils ··· 150mg <Package> Gelatin: 100mg Glycerin 30mg

[0087] (Formulation Example 2: Powder) The following ingredients were mixed and granulated in a conventional manner to produce 5 g stick granules. Bacillus subtilis C-3102 strain soybean culture 5% by mass Sodium carboxymethylcellulose: appropriate amount Dextrin - appropriate amount

[0088] (Formulation Example 3: Liquid) The following ingredients were mixed and 10 kg of water was added in a conventional manner to prepare a liquid formulation. Bacillus subtilis C-3102 strain soybean culture 100g · Liquid sugar ··· 4000g Sodium DL-tartrate 1g Citric acid 50g Vitamin C 50g Vitamin E 150g Cyclodextrin 25g Potassium chloride 5 g Magnesium sulfate 2 g [Accession number]

[0089] FERM BP-1096

Claims

1. 1. An agent for improving joint movement or relieving joint pain, comprising a bacterial cell and / or a culture of Bacillus subtilis.

2. 2. The method for improving joint movement or relieving joint pain according to claim 1, wherein the culture is a soybean culture.

3. 3. The agent for improving joint movement or relieving joint pain according to claim 1 or 2, which comprises spores of Bacillus subtilis.

4. 3. The agent for improving joint movement or relieving joint pain according to claim 1 or 2, wherein the Bacillus subtilis is Bacillus subtilis C-3102 strain (FERM BP-1096).

5. 3. The agent for improving joint movement or relieving joint pain according to claim 1 or 2, which is taken orally.

6. 2.0 x 10 per day ８ ~2.5 x 10 １１ 3. The agent for improving joint movement or relieving joint pain according to claim 1 or 2, which is formulated so that CFU of Bacillus subtilis can be ingested.

7. 2.0 x 10 per day ９ ~2.0 x 10 １０ 3. The agent for improving joint movement or relieving joint pain according to claim 1 or 2, which is formulated so that CFU of Bacillus subtilis can be ingested.

8. 1. A food, drink, or feed for improving joint movement or relieving joint pain, comprising a bacterial cell and / or a culture of Bacillus subtilis.

9. A pharmaceutical composition for improving joint movement or relieving joint pain, comprising a bacterial cell and / or a culture of Bacillus subtilis.

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