Osteoclast differentiation inhibitor

Abstract

To provide an agent suitable for applications, including the inhibition of osteoclast differentiation.SOLUTION: An agent contains at least one fatty acid selected from hydroxy C10-30 fatty acids and oxo C10-30 fatty acids.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent useful for inhibiting osteoclast differentiation, etc. [Background technology]

[0002] Osteoporosis is a disease (illness) in which bone mass decreases due to excessive bone resorption, and is caused by bone loss due to activated differentiation (proliferation) of osteoclasts.

[0003] Therefore, it is believed that by suppressing (inhibiting) the differentiation (proliferation) of osteoclasts, it is possible to improve (suppress), delay, or prevent osteoporosis.

[0004] The functions of fatty acids such as hydroxyoctadecanoic acid are currently being studied. For example, Patent Document 1 discloses that a specific fatty acid having a hydroxyl group or a carbonyl group is used as an anti-inflammatory agent. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2015 / 111701 Brochure Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide an agent, etc. that is useful for inhibiting osteoclast differentiation (proliferation) [or inhibiting TRAP (tartrate-resistant acid phosphatase) activity]. [Means for solving the problem]

[0007] Means for Solving the Problems The present inventors have conducted intensive research to achieve the above-mentioned object and have found that certain components are effective (useful) in inhibiting osteoclast differentiation (proliferation) [or inhibiting TRAP (tartrate-resistant acid phosphatase) activity], thereby completing the present invention.

[0008] That is, the present invention relates to the following inventions, etc. [1] Hydroxy fatty acids (especially hydroxy C 10-30 fatty acids) and oxo fatty acids (especially oxo C 10-30 an agent for inhibiting osteoclast differentiation and / or TRAP activity (an agent for inhibiting osteoclast differentiation and / or TRAP activity, an agent for use in at least one application selected from the group consisting of inhibition of osteoclast differentiation and inhibition of TRAP activity), comprising at least one fatty acid selected from the group consisting of fatty acids. [2] Hydroxy fatty acids (especially hydroxy C 10-30 fatty acids) and oxo fatty acids (especially oxo C 10-30 and (fats), and is intended for use in at least one application selected from the following (1) to (2). (1) Suppression of bone density loss and / or maintenance of bone density (bone mass) (2) Improvement (treatment), inhibition (inhibition of progression) and / or prevention of osteoporosis [3] Hydroxy fatty acids (especially hydroxy C 10-30 fatty acids) and oxo fatty acids (especially oxo C 10-30 A composition for inhibiting osteoclast differentiation and / or TRAP (tartrate-resistant acid phosphatase) activity, comprising at least one fatty acid selected from the group consisting of fatty acids. [4] Hydroxy fatty acids (especially hydroxy C 10-30 fatty acids) and oxo fatty acids (especially oxo C 10-30 A composition for use in at least one application selected from the following (1) to (2), comprising at least one fatty acid selected from the group consisting of carboxylic acids, carboxylic acids, and carboxylic acids. (1) Suppression of bone density loss and / or maintenance of bone density (bone mass) (2) Improvement (treatment), inhibition (inhibition of progression) and / or prevention of osteoporosis [5] Hydroxy C 12-24 Fatty acids and oxo-C 12-24The agent or composition according to any one of [1] to [4], comprising at least one fatty acid selected from fatty acids. [6] The agent or composition according to any one of [1] to [5], comprising at least one fatty acid selected from a hydroxy fatty acid having 16 carbon atoms, a hydroxy fatty acid having 18 carbon atoms, a hydroxy fatty acid having 20 carbon atoms, an oxo fatty acid having 16 carbon atoms, an oxo fatty acid having 18 carbon atoms, and an oxo fatty acid having 20 carbon atoms. [7] The agent or composition according to any one of [1] to [6], comprising at least one fatty acid selected from hydroxyoctadecanoic acid and oxooctadecanoic acid. [8] The agent or composition according to any one of [1] to [7], comprising at least one selected from 10-hydroxyoctadecanoic acid and 12-hydroxyoctadecanoic acid. [9] The agent or composition according to any one of [1] to [8], which contains 10-hydroxyoctadecanoic acid.

[10] The agent or composition according to any one of [1] to [9], which is for oral administration.

[11] The composition according to any one of [3] to

[10] , which is a food or drink.

[12] The composition according to any one of [3] to

[11] , which is a health food or supplement. Effect of the Invention

[0009] According to the present invention, it is possible to provide an agent useful for inhibiting osteoclast differentiation (proliferation) [or inhibiting TRAP (tartrate-resistant acid phosphatase) activity]. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] [Agent] The present invention provides an agent containing at least one fatty acid (hereinafter sometimes simply referred to as fatty acid) selected from hydroxy fatty acids and oxo fatty acids.

[0011] Examples of fatty acids include fatty acids having 8 or more carbon atoms, and representative examples include fatty acids having 10 or more carbon atoms (e.g., hydroxy C 10-30 Fatty acids, oxo-C 10-30 fatty acids), preferably fatty acids having 12 or more carbon atoms (e.g., hydroxy C 12-24 Fatty acids, oxo-C 12-24 fatty acid), more preferably a fatty acid having 14 or more carbon atoms (e.g., hydroxy C 14-22 Fatty acids, oxo-C 14-22 fatty acids), especially fatty acids with 16 or more carbon atoms (e.g., hydroxy C 16-20 Fatty acids, oxo-C 16-20 fatty acid).

[0012] The fatty acid may be either a saturated fatty acid or an unsaturated fatty acid. In particular, the hydroxy fatty acid may be a saturated fatty acid. In the unsaturated fatty acid, the number of unsaturated bonds may be 1 or more, and examples thereof include 1 to 6, 1 to 4, 1 to 3, 1 to 2, and 1.

[0013] The fatty acid may be either a chain fatty acid or a cyclic fatty acid, and in particular may be a chain fatty acid.

[0014] The chain fatty acid may be either a straight-chain fatty acid or a branched-chain fatty acid, and in particular may be a straight-chain fatty acid.

[0015] The fatty acid (number of carboxy groups) may be either a monocarboxylic acid or a polycarboxylic acid (for example, a di- or tetracarboxylic acid), preferably a mono- or dicarboxylic acid, in particular a monocarboxylic acid.

[0016] The hydroxy fatty acid (number of hydroxy groups) may be either a monohydroxy fatty acid or a polyhydroxy fatty acid (for example, a di- or tetrahydroxy fatty acid), preferably a mono- or dihydroxy fatty acid, in particular a monohydroxy fatty acid.

[0017] The oxo fatty acid (number of oxo groups) may be either a monooxo fatty acid or a polyoxo fatty acid (for example, a di- or tetraoxo fatty acid), preferably a mono- or dioxo fatty acid, in particular a monooxo fatty acid.

[0018] In hydroxy fatty acids, the position of the hydroxy group (substitution position) varies depending on the number of hydroxy groups, the type of fatty acid, etc., but may be either a terminal or internal position [for example, in hydroxyoctadecanoic acid (wherein the 1st position is a carboxy group), the terminal is position 18 and the internal position is positions 2 to 17 (e.g., positions 3 to 16, 5 to 15, 6 to 15)], and typically may be an internal position.

[0019] In oxo fatty acids, the position of the oxo group (substitution position) varies depending on the number of oxo groups and the type of fatty acid, but may be either a terminal or internal position [for example, in oxooctadecanoic acid (wherein position 1 is a carboxy group), the terminal is position 18 and the internal position is positions 2 to 17 (e.g., positions 3 to 16, 5 to 15, 6 to 15)], and typically may be internal.

[0020] The fatty acid may or may not have a substituent. The hydroxy fatty acid may have an oxo group.

[0021] Representative fatty acids include, for example, fatty acids with 18 carbon atoms, fatty acids with other than 18 carbon atoms (for example, fatty acids with about 10 to 30 carbon atoms (excluding 18 carbon atoms), such as 16 or 20 carbon atoms).

[0022] Examples of fatty acids having 18 carbon atoms include hydroxy fatty acids having 18 carbon atoms [e.g., hydroxyoctadecanoic acid (e.g., 10-hydroxyoctadecanoic acid, 12-hydroxyoctadecanoic acid, 10,12-dihydroxyoctadecanoic acid, 10,13-dihydroxy-octadecanoic acid, 10-oxo-13-hydroxy-octadecanoic acid), hydroxyoctadecenoic acid (e.g., 10-hydroxy-cis-15-octadecenoic acid, 10-hydroxy-cis-6-octadecenoic acid, 10-hydroxy-trans-11-octadecenoic acid, 13 -Hydroxy-cis-9-octadecenoic acid, 10,13-dihydroxy-cis-6-octadecenoic acid, 10,13-dihydroxy-cis-15-octadecenoic acid, 12-oxo-cis-9-octadecenoic acid, 10-oxo-13-hydroxy-cis-6-octadecenoic acid, 10-oxo-13-hydroxy-cis-15-octadecenoic acid, etc.), hydroxyoctadecapolyenoic acids (e.g., 10-hydroxy-cis-12-octadecenoic acid, 10-hydroxy-cis-12,cis-15-octadecadienoic acid, 10-hydroxy-cis-6-octadecenoic acid, 10-oxo-13-hydroxy-cis-15-octadecenoic acid, etc.), ,cis-12-octadecadienoic acid, 10-hydroxy-cis-6,cis-12,cis-15-octadecatrienoic acid, 10-hydroxy-cis-6,cis-15-octadecadienoic acid, 10-hydroxy-trans-11,cis-15-octadecadienoic acid, 10-hydroxy-cis-6,trans-11-octadecadienoic acid, 10-hydroxy-cis-6,trans-11,cis-15-octadecatrienoic acid, 13-hydroxy-cis-6,cis-9-octadecadienoic acid, 13-hydroxy-cis-9,cis-15-octadecadienoic acid fatty acids having 18 carbon atoms [e.g., oxooctadecanoic acid (e.g., 10-oxooctadecanoic acid, 12-oxooctadecanoic acid, 10,13-dihydroxy-cis-6,cis-15-octadecatrienoic acid, 10-oxo-13-hydroxy-cis-6,cis-15-octadecadienoic acid, 13-hydroxy-cis-5,cis-9-octadecadienoic acid, 13-hydroxy-trans-5,cis-9-octadecadienoic acid, etc.],13-dioxo-octadecanoic acid), oxooctadecenoic acids (e.g., 10-oxo-cis-12-octadecenoic acid, 10-oxo-cis-6-octadecenoic acid, 10-oxo-cis-15-octadecenoic acid, 10-oxo-trans-11-octadecenoic acid, 13-oxo-cis-9-octadecenoic acid, 10,13-dioxo-cis-6-octadecenoic acid, decenoic acid, 10,13-dioxo-cis-15-octadecenoic acid, etc.), oxooctadecapolyenoic acids (e.g., 10-oxo-cis-12,cis-15-octadecadienoic acid, 10-oxo-cis-6,cis-12-octadecadienoic acid, 10-oxo-cis-6,cis-12,cis-15-octadecatrienoic acid, 10-oxo-cis-6,cis- Examples of oxo fatty acids having 18 carbon atoms include 15-octadecadienoic acid, 10-oxo-cis-6,trans-11-octadecadienoic acid, 10-oxo-trans-11,cis-15-octadecadienoic acid, 10-oxo-cis-6,trans-11,cis-15-octadecadienoic acid, 10-oxo-cis-6,trans-11,cis-15-octadecatrienoic acid, 13-oxo-cis-6,cis-9-octadecadienoic acid, 13-oxo-cis-9,cis-15-octadecadienoic acid, 13-oxo-cis-6,cis-9,cis-15-octadecatrienoic acid, 10,13-dioxo-cis-6,cis-15-octadecadienoic acid, 13-oxo-cis-5,cis-9-octadecadienoic acid, 13-oxo-trans-5,cis-9-octadecadienoic acid, etc.

[0023] Examples of fatty acids having a carbon number other than 18 (e.g., about 10 to 30 carbon numbers (excluding 18 carbon numbers), such as 16 and 20 carbon numbers) include hydroxyhexadecanoic acid (e.g., 10-hydroxy-hexadecanoic acid), oxohexadecanoic acid (e.g., 10-oxo-hexadecanoic acid), hydroxyeicosenoic acid (e.g., 12-hydroxy-cis-14-eicosenoic acid, 15-hydroxy-cis-11-eicosenoic acid), hydroxyeicosapolyenoic acid (e.g., 12-hydroxy-cis-14,cis-17-eicosadienoic acid, 12-hydroxy-cis-15,cis-18-eicosadienoic acid, 12-hydroxy-cis-16,cis-19-eicosadienoic acid, 12-hydroxy-cis-18,cis-20-eicosadienoic acid, 12-hydroxy-cis-18,cis-21-eicosadienoic acid, 12-hydroxy-cis-18,cis-22-eicosadienoic acid, 12-hydroxy-cis-18,cis-23-eicosadienoic acid, 12-hydroxy-cis-18,cis-24-eicosadienoic acid, 12-hydroxy-cis-18,cis-25-eicosadienoic acid, 12-hydroxy-cis-18,cis-26-eicosadienoic acid, 12-hydroxy-cis-18,cis-27-eicosadienoic acid, 12-hydroxy-cis-18,cis-28-eicosadienoic acid, 12-hydroxy-cis-18,cis-29-eicosadienoic acid, 12-hydroxy-cis-18,cis-29-eicosadienoic acid, 12- 12-hydroxy-cis-8,cis-14-eicosadienoic acid, 12-hydroxy-cis-5,cis-8-eicosadienoic acid, 12-hydroxy-cis-8,cis-14,cis-17-eicosatrienoic acid, 12-hydroxy-cis-5,cis-8,cis-14-eicosatrienoic acid, 15-hydroxy-cis-11,cis-17-eicosadienoic acid, 15-hydroxy-cis-8,cis-11-eicosadienoic acid, 15-hydroxy-cis-5,cis-8,cis-11-eicosatrienoic acid, 15-hydroxy-cis-8,cis-1 1,cis-17-eicosatrienoic acid, 15-hydroxy-cis-5,cis-11-eicosadienoic acid, 15-hydroxy-cis-5,cis-11,cis-17-eicosatrienoic acid), oxoeicosenoic acids (e.g., 12-oxo-cis-14-eicosadienoic acid, 15-oxo-cis-11-eicosadienoic acid), oxoeicosapolyenoic acids (e.g., 12-oxo-cis-14,cis-17-eicosadienoic acid, 12-oxo-cis-8,cis-14-eicosadienoic acid, 12-oxo-cis-5,cis-8-eicosadienoic acid , 12-oxo-cis-8,cis-14,cis-17-eicosatrienoic acid, 12-oxo-cis-5,cis-8,cis-14-eicosatrienoic acid, 15-oxo-cis-11,cis-17-eicosadienoic acid, 15-oxo-cis-8,cis-11-eicosadienoic acid, 15-oxo-cis-5,cis-8,cis-11-eicosatrienoic acid, 15-oxo-cis-8,cis-11,cis-17-eicosatrienoic acid, 15-oxo-cis-5,cis-11-eicosadienoic acid or 15-oxo-cis-5,cis-11,Examples include fatty acids with 18 carbon atoms (such as fatty acids with 16 or 20 carbon atoms), such as cis-17-eicosatrienoic acid.

[0024] The fatty acids may be used alone or in combination of two or more.

[0025] Of these fatty acids, hydroxy C 10-30 Fatty acids (e.g., hydroxy C 12-24 Fatty acids, preferably hydroxy C 16-20 fatty acids) and oxo C 10-30 Fatty acids (e.g., oxoC 12-24 Fatty acids, preferably oxo-C 16-20 At least one fatty acid selected from the group consisting of fatty acids may be preferably used.

[0026] Among these, at least one fatty acid selected from hydroxy fatty acids having 16 carbon atoms, hydroxy fatty acids having 18 carbon atoms, hydroxy fatty acids having 20 carbon atoms, oxo fatty acids having 16 carbon atoms, oxo fatty acids having 18 carbon atoms, and oxo fatty acids having 20 carbon atoms, and in particular, at least one fatty acid selected from hydroxyoctadecanoic acid and oxooctadecanoic acid (for example, hydroxyoctadecanoic acids such as 10-hydroxyoctadecanoic acid and 12-hydroxyoctadecanoic acid) may be preferably used.

[0027] When hydroxyoctadecanoic acid is used, 10-hydroxyoctadecanoic acid may be preferably used, particularly from the viewpoint of safety (balance between safety and the function described below) and the like.

[0028] The fatty acids to be used may be commercially available products or those synthesized by conventional or known methods.

[0029] (Application of the agent) The agent of the present invention can be used for specific purposes.

[0030] First, the agent of the present invention can be used as an inhibitor of osteoclast differentiation [and / or an inhibitor of TRAP (tartrate-resistant acid phosphatase) activity]. In addition, the agent of the present invention may be used for applications related (or reported to be related) to the inhibition of osteoclast differentiation (and / or inhibition of TRAP activity), for example, at least one application selected from the following applications (1) and (2): (1) Suppression of decline in bone density (bone mass) and / or maintenance of bone density (bone mass) (2) Improvement (treatment), inhibition (inhibition of progression) and / or prevention of osteoporosis

[0031] [Composition, dosage form, etc.] The present invention also includes compositions comprising said fatty acids (or agents).

[0032] In the composition, the aspects (specific aspects, preferred aspects, etc.) of the fatty acid (or agent) are the same as those described above.

[0033] Such compositions can also be used for the same functions and applications as the above-mentioned agents, for example, for inhibiting osteoclast differentiation (and / or inhibiting TRAP activity), inhibiting and / or maintaining a decrease in bone density (bone mass), improving (treating), inhibiting (inhibiting the progression of), and / or preventing osteoporosis, etc.

[0034] In addition, such functions and uses may have the fatty acid as an active ingredient, similar to the agent.

[0035] The intake (administration) form of the fatty acid (or agent or composition) is not particularly limited, and may be oral (for oral use) or parenteral (for parenteral use). Examples of parenteral administration (parenteral intake) include rectal administration and injection administration (e.g., intravenous administration, intraspinal administration, intramuscular administration, subcutaneous administration, intraperitoneal administration, intraarticular administration, intradermal administration, and intralesional administration).

[0036] In particular, from the standpoint of ease of ingestion (administration), etc., the fatty acid (or agent or composition) may be for oral use.

[0037] Subjects to which the fatty acid (or agent or composition) is ingested (taken, administered) include humans and non-human animals (e.g., dogs, cats, etc.). The subject may be a specific subject (e.g., women, elderly people, patients or sick people (e.g., patients with osteoporosis), etc.).

[0038] The intake amount (dosage, dosage) of the fatty acid (agent or composition) can be selected depending on the severity of the disease or symptoms, and may be, for example, about 0.01 mg or more (e.g., 0.01 to 1000 mg), preferably 0.1 mg or more (e.g., 0.1 to 100 mg), and more preferably 1 mg or more (e.g., 1 to 10 mg) of fatty acid per day.

[0039] The agent or composition may be used for a specific application, for example, as a medicine, a quasi-drug, a food or drink, or the like.

[0040] Examples of food and beverage products (drinks and foods) include general food and beverage products, as well as health foods (including functional health foods (foods for specified health uses, foods with nutrient functions, and foods with functional claims)), supplements (nutritional supplements), feed, etc.

[0041] Because of the above-mentioned functions, the compound is suitable for use in health foods, supplements, and the like, among other foods and beverages.

[0042] The composition may contain other components (components other than the fatty acids).

[0043] The other ingredients can be appropriately selected depending on the form of intake and the mode of application.

[0044] One embodiment of the other components includes components (additives) used in formulation, etc., such as carriers, excipients, binders, disintegrants, lubricants, coating agents, colorants, flavorings, stabilizers, emulsifiers, absorption enhancers, surfactants, pH adjusters, preservatives, and antioxidants.

[0045] Examples of the carrier include, but are not limited to, animal and vegetable oils such as soybean oil, beef tallow, and synthetic glyceride; hydrocarbons such as liquid paraffin, squalane, and solid paraffin; ester oils such as octyldodecyl myristate and isopropyl myristate; higher alcohols such as cetostearyl alcohol and behenyl alcohol; silicon resins; silicone oils; surfactants such as polyoxyethylene fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, and polyoxyethylene polyoxypropylene block copolymers; water-soluble polymers such as hydroxyethyl cellulose, polyacrylic acid, carboxyvinyl polymers, polyethylene glycol, polyvinylpyrrolidone, and methylcellulose; lower alcohols such as ethanol and isopropanol; polyhydric alcohols such as glycerin, propylene glycol, dipropylene glycol, and sorbitol; sugars such as glucose and sucrose; inorganic powders such as silicic anhydride, aluminum magnesium silicate, and aluminum silicate; and purified water.

[0046] Examples of excipients include lactose, corn starch, sucrose, glucose, mannitol, sorbitol, crystalline cellulose, and silicon dioxide.

[0047] Examples of binders include polyvinyl alcohol, gelatin, methyl cellulose, ethyl cellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyvinyl acetal diethyl amino acetate, and corn starch.

[0048] Examples of disintegrants include corn starch, low-substituted hydroxypropylcellulose, crospovidone, crystalline cellulose, precipitated calcium carbonate, croscarmellose sodium, calcium citrate, dextrin, pectin, and calcium carboxymethylcellulose.

[0049] Examples of the lubricant include magnesium stearate, talc, polyethylene glycol, light anhydrous silicic acid, and sucrose fatty acid esters. Examples of the flavoring agent include cocoa powder, menthol, aromatic powder, peppermint oil, borneol, and cinnamon powder.

[0050] In particular, when used in foods, beverages, etc., other ingredients may include, for example, excipients (e.g., wheat starch, corn starch, cellulose, lactose, sucrose, mannitol, sorbitol, xylitol, pregelatinized starch, casein, magnesium aluminosilicate, calcium silicate, etc.), binders (e.g., pregelatinized starch, hydroxypropylmethylcellulose, polyvinylpyrrolidone, etc.), disintegrants (e.g., cellulose, hydroxypropylcellulose, corn starch, etc.), flow inhibitors, etc. Other additives that may be used include organic solvents (e.g., light anhydrous silicic acid, sucrose fatty acid esters, etc.), oils (e.g., vegetable oils such as soybean oil, sesame oil, olive oil, linseed oil, perilla oil, rapeseed oil, coconut oil, corn oil, etc., or oils derived from animals or fish), nutrients (e.g., various minerals, various vitamins, amino acids), flavors, sweeteners, flavorings, colorants, solvents (ethanol), salts, surfactants, pH regulators, buffers, antioxidants, stabilizers, gelling agents, thickeners, lubricants, encapsulating agents, suspending agents, coating agents, preservatives, etc.

[0051] The other components may be used alone or in combination of two or more.

[0052] The form of the agent or composition (formulation form) is not particularly limited, and examples thereof include tablets, powders, fine granules, granules, capsules (soft capsules, hard capsules, etc.), liquids (suspensions, syrups, etc.), troches, jellies, suppositories, injections, sprays, etc.

[0053] In particular, when used as health foods and the like, for example, tablets, powders, fine granules, granules, capsules, emulsions, jellies, and the like are suitable.

[0054] Furthermore, when the fatty acid (or agent or composition) is used by adding (mixing, blending) to a food or drink (general food or drink), the food or drink is not particularly limited, but examples thereof include foods [e.g., noodles (buckwheat, udon, Chinese noodles, instant noodles, etc.), confectioneries (candy, candy, gum, chocolate, snacks (potato chips, etc.), biscuits, cookies, gummies, jellies, jams, butter, cream (cream puffs, etc.), cakes, etc.), breads, processed seafood or livestock foods (kamaboko, ham, sausages, etc.), These include dairy products (processed milk, fermented milk, etc.), fats and oil-processed foods (salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressings, etc.), seasonings (sauces, dressings, etc.), retort foods (curry, stew, rice bowls, porridge, rice porridge, etc.), frozen desserts (ice cream, sorbet, shaved ice, etc.), fried foods (croquettes, french fries, fried chicken, etc.), beverages (tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, etc.).

[0055] The proportion of the fatty acid (or agent or composition) in the food or beverage can be selected depending on the type of food or beverage and the intake amount, and may be, for example, 0.0001 mass% or more (e.g., 0.001 to 30 mass%), 0.003 mass% or more (e.g., 0.005 to 20 mass%), 0.01 mass% or more (e.g., 0.05 to 10 mass%), etc.

[0056] <Method> As described above, the fatty acid (or agent or composition) can be used in various applications. Therefore, the present invention also includes methods corresponding to the applications.

[0057] First, in the method of the present invention, the fatty acid (or agent or composition) is ingested (administered, taken) by a subject to inhibit osteoclast differentiation [and / or inhibit TRAP (tartrate-resistant acid phosphatase) activity].

[0058] As described above, inhibition of osteoclast differentiation (and / or inhibition of TRAP activity) can improve (treat, suppress) associated symptoms and diseases.

[0059] Therefore, the present invention includes a method for improving (treating, suppressing) symptoms and diseases associated with inhibition of osteoclast differentiation (and / or inhibition of TRAP activity) by having a subject ingest (administer, take) the fatty acid (or agent or composition).

[0060] Examples of such methods include methods corresponding to the above-mentioned uses (1) and (2), that is, the following (1A) and (2A), etc.

[0061] (1A) A method for inhibiting a decrease in bone density (bone mass) and / or maintaining bone density (bone mass) by having a subject ingest (administer, take) the fatty acid (or agent or composition).

[0062] (2A) A method for improving (treating), suppressing (suppressing the progression of) and / or preventing osteoporosis by having a subject ingest (administer, take) the fatty acid (or agent or composition).

[0063] In the above-mentioned method, the specific form and intake amount of the fatty acid (or agent or composition) may be the same as those described above. EXAMPLES

[0064] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these.

[0065] Example 1: TRAP activity of 12-hydroxyoctadecanoic acid Mouse macrophage-like cells (RAW264.7) were seeded onto a 96-well plate and cultured overnight at 37°C under 5% CO2 in α-MEM medium (Fujifilm Wako Pure Chemical Industries, Ltd.) supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin. Receptor activator of nuclear factor kappa-B ligand (hereinafter referred to as RANKL) was added to the medium at 10ng / mL, and 12-hydroxyoctadecanoic acid was added at 50μM, and the cells were cultured for 48 hours. After preparing an extract solution from the cultured cells, 50μL of the substrate solution of the TRACP and ALP assay kit (manufactured by Takara Bio Inc.) was added, and the cells were incubated at 37℃ for 30 minutes. After adding 50μL of 0.5N NaOH solution, the absorbance at 405nm was measured with a microplate reader to evaluate the TRAP activity.

[0066] The absorbance when cultured without adding anything was 1.09, the absorbance when cultured with only RANKL (10 ng / mL) added was 1.93, and the absorbance when cultured with RANKL and 12-hydroxyoctadecanoic acid was added was 0.89.

[0067] This confirmed that the addition of 12-hydroxyoctadecanoic acid suppressed the TRAP activity that was increased by RANKL treatment.

[0068] (Example 2) TRAP activity of 10-hydroxyoctadecanoic acid When TRAP activity was evaluated in the same manner as in Example 1, except that 12-hydroxyoctadecanoic acid was changed to 10-hydroxyoctadecanoic acid, the absorbance was 1.37 when RANKL and 10-hydroxyoctadecanoic acid were added. This confirmed that 10-hydroxyoctadecanoic acid also suppressed the TRAP activity that was increased by RANKL treatment.

[0069] (Reference Example 1) TRAP activity of oleic acid When TRAP activity was evaluated in the same manner as in Example 1 except that 12-hydroxyoctadecanoic acid was changed to oleic acid, the absorbance was 1.81 when RANKL and oleic acid were added. This confirmed that the addition of oleic acid did not substantially suppress the TRAP activity increased by RANKL treatment.

[0070] (Reference Example 2) TRAP activity of octadecanoic acid When TRAP activity was evaluated in the same manner as in Example 1 except that 12-hydroxyoctadecanoic acid was changed to octadecanoic acid, the absorbance was 2.12 when RANKL and octadecanoic acid were added. This confirmed that the addition of octadecanoic acid did not at all suppress the TRAP activity increased by RANKL treatment, or rather promoted it.

[0071] (Example 3) Ratio change 1 TRAP activity was evaluated in the same manner as in Example 1, except that the amount of 12-hydroxyoctadecanoic acid added was 15 μM. The absorbance when RANKL and 12-hydroxyoctadecanoic acid were added was 1.29. This confirmed that TRAP activity, which was increased by RANKL treatment, was suppressed even when the ratio was changed.

[0072] (Example 4) Ratio change 2 In Example 2, TRAP activity was evaluated in the same manner as in Example 2, except that the amount of 10-hydroxyoctadecanoic acid added was 15 μM. The absorbance when RANKL and 10-hydroxyoctadecanoic acid were added was 1.78. This confirmed that TRAP activity, which was increased by RANKL treatment, was suppressed even when the ratio was changed.

[0073] (Reference Example 3) Ratio change 3 When TRAP activity was evaluated in the same manner as in Reference Example 1, except that the amount of oleic acid added was 15 μM, the absorbance when RANKL and oleic acid were added was 2.04. This confirmed that, even if the ratio of oleic acid was changed, the TRAP activity increased by RANKL treatment was not suppressed at all or was rather promoted.

[0074] (Reference Example 4) Ratio change 4 In Reference Example 1, TRAP activity was evaluated in the same manner as in Reference Example 2, except that the amount of octadecanoic acid added was 15 μM. The absorbance when RANKL and octadecanoic acid were added was 2.10. This confirmed that, with octadecanoic acid, even if the ratio was changed, the TRAP activity increased by RANKL treatment was not suppressed at all or was rather promoted.

[0075] (Example 5) Ratio change 5 TRAP activity was evaluated in the same manner as in Example 1, except that the amount of 12-hydroxyoctadecanoic acid added was 5 μM. The absorbance when RANKL and 12-hydroxyoctadecanoic acid were added was 1.40. This confirmed that even at a lower ratio, the TRAP activity increased by RANKL treatment was suppressed.

[0076] Example 6 Cytotoxicity Mouse macrophage-like cells (RAW264.7) were seeded onto a 96-well plate and cultured overnight at 37°C under 5% CO2 in α-MEM medium (Fujifilm Wako Pure Chemical Industries, Ltd.) supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin. RANKL was added to the medium at a concentration of 10 ng / mL, and 12-hydroxyoctadecanoic acid, 10-hydroxyoctadecanoic acid, oleic acid or octadecanoic acid was added to the medium at the concentrations shown in the table, followed by culturing for 48 hours.

[0077] WST-8 (Dojindo Laboratories) was added to the cultured cells, and 30 minutes later, the absorbance at 450 nm was measured using a microplate reader to evaluate the cell number.

[0078] The results of absorbance measurement using WST-8 are shown in the table below. For comparison, the results of culturing without adding anything (no addition) and culturing with only RANKL (10 ng / mL) are also shown.

[0079] [Table 1]

[0080] As is clear from the results in the above table, among hydroxyoctadecanoic acids, 12-hydroxyoctadecanoic acid was shown to have the possibility of being cytotoxic under certain conditions. Therefore, from the viewpoint of high safety (achieving both high safety and inhibition of osteoclast differentiation), it was found that 10-hydroxyoctadecanoic acid is particularly preferable.

[0081] Specific examples of the composition of the present invention are given below.

[0082] Formulation example 1: Soft drinks 10-Hydroxyoctadecanoic acid 0.5g 15.0g honey Citric acid 0.1g dl-Malic acid 0.1g D-sorbitol liquid (70%) 10.0g Sodium benzoate 0.1g Fragrance (appropriate amount) Purified water, remainder to make 100g The above ingredients were mixed uniformly to obtain a health drink.

[0083] Formulation Example 2: Tablets 10-Hydroxyoctadecanoic acid 1.0mg Lactose 94.0mg Corn starch 34.0mg Crystalline cellulose 20.0mg Active absorbable calcium (from oyster shells) 10.0mg Magnesium stearate 1.0mg The components were thoroughly mixed in the above-mentioned ratio, and the mixture was compressed to obtain tablets.

[0084] Prescription example 3: Powder 10-Hydroxyoctadecanoic acid 1.0mg Lactose 981.0mg Hydroxypropyl cellulose 4.0mg Soft anhydrous silicic acid 5.0mg First, mix 10-hydroxyoctadecanoic acid and lactose thoroughly in the above ratio, then Hydroxypropyl cellulose is added and granulated. After drying, this is granulated and soft anhydrous silica is added. The acid was added and further mixed thoroughly to obtain a powder.

[0085] Formulation Example 4: Capsules 10-Hydroxyoctadecanoic acid 150.0mg Lactose 70.0mg Corn starch 38.0mg Magnesium stearate 2.0mg The components were thoroughly mixed in the above-mentioned ratio and filled into capsules to obtain capsules.

[0086] Formulation example 5: Soft capsule 10-Hydroxyoctadecanoic acid 50.0mg Refined soybean oil 130.0mg Tocopherol 20.0mg The ingredients were thoroughly mixed in the above-mentioned ratio and filled into capsules to obtain soft capsules. [Industrial Applicability]

[0087] The agent of the present invention can be used as an osteoclast differentiation inhibitor or the like.

Claims

1. Hydroxy C １０－３０ Fatty acids and oxo C １０－３０ An agent for inhibiting osteoclast differentiation and / or TRAP activity, comprising at least one fatty acid selected from fatty acids.

2. Hydroxy C １０－３０ Fatty acids and oxo C １０－３０ An agent comprising at least one fatty acid selected from fatty acids, for use in at least one application selected from the following (1) to (2): (1) Inhibition of bone density loss and / or maintenance of bone density (2) Improvement, inhibition, and / or prevention of osteoporosis

3. Hydroxy C １０－３０ Fatty acids and oxo C １０－３０ A composition for inhibiting osteoclast differentiation and / or TRAP activity, comprising at least one fatty acid selected from fatty acids.

4. Hydroxy C １０－３０ Fatty acids and oxo C １０－３０ A composition for use in at least one application selected from the following (1) and (2), comprising at least one fatty acid selected from fatty acids: (1) Inhibition of bone density loss and / or maintenance of bone density (2) Improvement, inhibition, and / or prevention of osteoporosis

5. Hydroxy C １２－２４ Fatty acids and oxo C １２－２４ The agent or composition according to any one of claims 1 to 4, comprising at least one fatty acid selected from fatty acids.

6. The agent or composition according to any one of claims 1 to 4, comprising at least one fatty acid selected from a hydroxy fatty acid having 16 carbon atoms, a hydroxy fatty acid having 18 carbon atoms, a hydroxy fatty acid having 20 carbon atoms, an oxo fatty acid having 16 carbon atoms, an oxo fatty acid having 18 carbon atoms, and an oxo fatty acid having 20 carbon atoms.

7. The agent or composition according to any one of claims 1 to 4, comprising at least one fatty acid selected from hydroxyoctadecanoic acid and oxooctadecanoic acid.

8. The agent or composition according to any one of claims 1 to 4, comprising at least one selected from 10-hydroxyoctadecanoic acid and 12-hydroxyoctadecanoic acid.

9. The agent or composition according to any one of claims 1 to 4, comprising 10-hydroxyoctadecanoic acid.

10. The agent or composition according to any one of claims 1 to 4, which is for oral use.

11. The composition according to claim 3 or 4, which is a food or drink.

12. The composition according to claim 3 or 4, which is a health food or supplement.

Images