JP6800386B1 - Composition for improving bone metabolism - Google Patents

Abstract

A composition for improving bone metabolism is provided. Specifically, a composition for improving bone metabolism, a food or drink for improving bone metabolism, which contains at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. , Or a drug is provided.

Description

The present invention relates to a composition for improving bone metabolism. The present invention also relates to foods and drinks or pharmaceuticals used for improving bone metabolism. Furthermore, the present invention relates to a method for imparting a bone metabolism improving effect to a food or drink or a pharmaceutical product.

In humans, bone is normally remodeled by maintaining a balance between osteoclasts and osteoblasts, but when this balance is lost due to aging, menopause, diabetes, etc., bone resorption such as osteoporosis occurs. It is easy to develop sexual diseases. In this state, the differentiation of osteoclasts is promoted by the differentiation of osteoblasts, and the balance is tilted in the direction of osteolysis. As a result, bone mass is reduced, bones become brittle, and fractures are likely to occur. Or.

Medication is the mainstream for such bone resorption diseases. Bone resorption inhibitors, such as bisphosphonates, currently prescribed as drugs for osteoporosis, increase bone mass by suppressing the activity of osteoclasts, but at the same time reduce osteoblast differentiation factors. It also suppresses the formation of new bone. Therefore, if it is continued for a long period of time, only old bone remains and the bone deteriorates, and there is a problem of side effects such as necrosis of the mandible and fracture of the femur.

On the other hand, in the field of health foods, many functional foods and supplements have been developed for the purpose of preventive treatment of osteoporosis and bone strengthening using food-derived substances as active ingredients, mainly in consideration of safety. (Patent Documents 1 to 4).

However, these functional foods and supplements are often not sufficiently effective, and in the industry, effective prevention and / or treatment of bone resorption diseases (osteoporosis, bone loss, etc.) such as humans. It is still desired to develop further ingredients (especially food-derived ingredients) that are highly safe and that enable such things, and in particular, ingredients that are easy to use in foods and that exert the effect of suppressing osteoclast differentiation are required. Has been done.

JP-A-10-14653 Japanese Patent Application Laid-Open No. 11-0121992 JP-A-2009-09618 JP-A-2016-166155

An object of the present invention is to provide a technique for improving bone metabolism. More specifically, it is an object of the present invention to provide a composition for improving bone metabolism. Secondly, it aims to provide foods and drinks or medicines used for improving bone metabolism. Thirdly, it is an object of the present invention to provide a method for imparting a bone metabolism improving effect to foods and drinks or pharmaceuticals.

In order to achieve the above object, the present inventors have found as a result of diligent research that monosaccharides or sugar alcohols exert an action of improving bone metabolism easily and effectively, and further improvements are made in this book. The invention has been completed.

The present invention has been completed by further studying based on such findings, and has the following embodiments.

(I) Composition for improving bone metabolism (I-1) For improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. Composition.
(I-2) The improvement of bone metabolism is due to one or more actions selected from the group consisting of an osteoclast differentiation inhibitory action, a bone component maintenance action, and a bone resorption inhibitory action, according to (I-1). Composition for improving bone metabolism.
(I-3) The monosaccharide having 4 to 6 carbon atoms is at least one monosaccharide selected from the group consisting of xylose, ribose, fructose, psicose, sorbose, galactose, fucose, glucose, and rhamnose. The composition for improving bone metabolism according to I-1) or (I-2).
(I-4) The sugar alcohol having 4 to 6 carbon atoms is at least one sugar alcohol selected from the group consisting of erythritol, sorbitol, mannitol, and inositol, (I-1) or (I-2). The composition for improving bone metabolism described in 1.

(II) Foods and drinks for improving bone metabolism, or pharmaceutical products (II-1) Bone containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. Foods and drinks for improving metabolism, or medicines.
(II-2) The improvement of bone metabolism is due to one or more actions selected from the group consisting of osteoclast differentiation inhibitory action, bone component maintenance action, and bone resorption inhibitory action, according to (II-1). Foods and drinks for improving bone metabolism, or medicines.
(II-3) The monosaccharide having 4 to 6 carbon atoms is at least one monosaccharide selected from the group consisting of xylose, ribose, fructose, psicose, sorbose, galactose, fucose, glucose, and rhamnose. Foods and drinks for improving bone metabolism or pharmaceuticals according to II-1) or (II-2).
(II-4) The sugar alcohol having 4 to 6 carbon atoms is at least one sugar alcohol selected from the group consisting of erythritol, sorbitol, mannitol, and inositol, (II-1) or (II-2). Foods and drinks for improving bone metabolism or pharmaceuticals described in.
(II-5) Described in any of (II-1) to (II-4), which is administered or ingested to a subject having or suspected to have an abnormal bone metabolism. Foods and drinks for improving bone metabolism, or medicines.
(II-6) Any of (II-1) to (II-5), which is administered or ingested to a subject having or suspected to have a bone resorption disease. Foods and drinks for improving bone metabolism or pharmaceutical products to be described.
(II-7) The food or drink for improving bone metabolism or a pharmaceutical product according to (II-6), which is a composition for treating or preventing a bone resorption disease.
(II-8) Any of (II-1) to (II-7), which is administered or ingested to a subject who has decreased bone mass or is suspected of having decreased bone mass. Foods and drinks for improving bone metabolism or pharmaceutical products described in.
(II-9) The food or drink for improving bone metabolism or a pharmaceutical product according to any one of (II-1) to (II-8), which is a composition for increasing bone mass.

(III) Method for imparting bone metabolism improving effect to food or drink or pharmaceutical product (III-1) At least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. A method for imparting a bone metabolism improving effect to a food or drink or a medicine, which comprises adding a seed to the food or medicine.
(III-2) Described in (III-1), wherein the bone metabolism improving action is one or more actions selected from the group consisting of an osteoclast differentiation inhibitory action, a bone component maintaining action, and a bone resorption suppressing action. Method.
(III-3) The monosaccharide having 4 to 6 carbon atoms is at least one monosaccharide selected from the group consisting of xylose, ribose, fructose, psicose, sorbose, galactose, fucose, glucose, and rhamnose. The method according to III-1) or (III-2).
(III-4) The sugar alcohol having 4 to 6 carbon atoms is at least one sugar alcohol selected from the group consisting of erythritol, sorbitol, mannitol, and inositol, (III-1) or (III-2). The method described in.

(IV) Method for improving bone metabolism (IV-1) A composition containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. A method of improving bone metabolism in a subject who needs the drug by administering or ingesting it.
(IV-2) The method according to (IV-1), wherein the improvement of bone metabolism is one or more actions selected from the group consisting of an osteoclast differentiation inhibitory action, a bone component maintenance action, and a bone resorption inhibitory action. ..
(IV-3) The monosaccharide having 4 to 6 carbon atoms is at least one monosaccharide selected from the group consisting of xylose, ribose, fructose, psicose, sorbose, galactose, fucose, glucose, and rhamnose. The method according to IV-1) or (IV-2).
(IV-4) The sugar alcohol having 4 to 6 carbon atoms is at least one sugar alcohol selected from the group consisting of erythritol, sorbitol, mannitol, and inositol, (IV-1) or (IV-2). The method described in.
(IV-5) The method according to any one of (IV-1) to (IV-4), wherein the composition is a food or drink or a pharmaceutical product.
(IV-6) The method according to any one of (IV-1) to (IV-5), wherein the subject has or is suspected of having an abnormal bone metabolism.
(IV-7) The method according to any one of (IV-1) to (IV-6), wherein the subject has or is suspected of having a bone resorption disease. ..
(IV-8) The method according to (IV-7), which is a method for treating or preventing a bone resorption disease of the subject.
(IV-9) Described in any of (IV-1) to (IV-8), wherein the subject is a subject having decreased bone mass or is suspected of having decreased bone mass. how to.
(IV-10) The method according to any one of (IV-1) to (IV-9), which is a method for increasing the bone mass of the subject.

(V) Monosaccharides used to improve bone metabolism, or sugar alcohols (V-1) compositions used to improve bone metabolism in subjects.
The composition comprises at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms as active ingredients.
(V-2) The improvement of bone metabolism is due to one or more actions selected from the group consisting of osteoclast differentiation inhibitory action, bone component maintenance action, and bone resorption inhibitory action, according to (V-1). Composition to be made.
(V-3) A monosaccharide having 4 to 6 carbon atoms is at least one monosaccharide selected from the group consisting of xylose, ribose, fructose, psicose, sorbose, galactose, fucose, glucose, and rhamnose. The composition according to V-1) or (V-2).
(V-4) The sugar alcohol having 4 to 6 carbon atoms is at least one sugar alcohol selected from the group consisting of erythritol, sorbitol, mannitol, and inositol, (V-1) or (V-2). The composition described in.
(V-5) The method according to any one of (V-1) to (V-4), wherein the composition is a food additive, a food or drink, or a pharmaceutical product.
(V-6) The composition according to any one of (V-1) to (V-5), wherein the subject has or is suspected of having an abnormal bone metabolism.
(V-7) The composition according to any one of (V-1) to (V-6), wherein the subject has or is suspected of having a bone resorption disease. Stuff.
(V-8) The composition according to (V-7), which is used to treat or prevent a bone resorption disease.
(V-9) Described in any of (V-1) to (V-8), wherein the subject is a subject having decreased bone mass or is suspected of having decreased bone mass. Composition to be made.
(V-10) The composition according to any one of (V-1) to (V-9), which is used to increase bone mass.

(VI) Use of monosaccharides for producing a composition for improving bone metabolism, or sugar alcohol (VI-1) Monosaccharides having 4 to 6 carbon atoms for producing a composition for improving bone metabolism of a subject, And the use of at least one selected from the group consisting of sugar alcohols having 4 to 6 carbon atoms.
(VI-2) Described in (VI-1), the improvement of bone metabolism is due to one or more actions selected from the group consisting of an osteoclast differentiation inhibitory action, a bone component maintenance action, and a bone resorption inhibitory action. Use to.
(VI-3) A monosaccharide having 4 to 6 carbon atoms is at least one monosaccharide selected from the group consisting of xylose, ribose, fructose, psicose, sorbose, galactose, fucose, glucose, and rhamnose. Use as described in VI-1) or (VI-2).
(VI-4) The sugar alcohol having 4 to 6 carbon atoms is at least one sugar alcohol selected from the group consisting of erythritol, sorbitol, mannitol, and inositol, (VI-1) or (VI-2). Use described in.
(VI-5) The use according to any one of (VI-1) to (VI-4), wherein the composition is a food additive, food or drink or pharmaceutical product.
(VI-6) The use according to any one of (VI-1) to (VI-5), wherein the subject has or is suspected of having an abnormal bone metabolism.
(VI-7) The use according to any one of (VI-1) to (VI-6), wherein the subject has or is suspected of having a bone resorption disease. ..
(VI-8) The use according to (VI-7), wherein the composition is for treating or preventing a bone resorption disorder.
(VI-9) Described in any of (VI-1) to (VI-8), wherein the subject is a subject having decreased bone mass or is suspected of having decreased bone mass. Use to.
(VI-10) The use according to any of (VI-1) to (VI-9), wherein the composition is for increasing bone mass.

According to the present invention, it is possible to provide a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. .. In addition, foods and drinks or medicines used for improving bone metabolism can be provided. Furthermore, it is possible to impart a bone metabolism improving effect to foods and drinks or pharmaceutical products. By ingesting foods and drinks for improving bone metabolism or pharmaceuticals of the present invention, the differentiation of osteoclasts is suppressed in humans and the like, thereby improving the balance of bone metabolism and bone resorption diseases (osteoporosis, Bone loss, etc.) can be effectively prevented and / or treated.

It is a graph which showed the number of differentiated cells into osteoclasts in Experimental Example 1. It is a graph which showed the toxicity evaluation result with respect to the osteoclast in Experimental Example 2. It is a graph which showed the number of differentiated cells into osteoclasts in Experimental Example 3. It is a graph which showed the toxicity evaluation result with respect to the osteoclast in Experimental Example 4.

The monosaccharide having 4 to 6 carbon atoms is not particularly limited as long as it has 4, 5, or 6 carbon atoms. The monosaccharide may be an aldose, a ketose, or a deoxy sugar. Further, the monosaccharide may be a D-form, an L-form, or a mixture of a D-form and an L-form. Examples of monosaccharides having 4 to 6 carbon atoms include 4-carbon sugars such as erythrose, threose, and elittlerose; 5-carbon sugars such as xylose, ribose, arabinose, lixose, ribulose, xylose, and deoxyribose; 6 charcoal such as sorbose, tagatose, galactose, allose, altrose, glucose, mannose, growth, idose, talose, ramnorth, fucose, arometilose, quinovose, anti-allose, taromethyrose, jigitoki sauce, ribulose, abecose, palatose, coritose, ascarirose, etc. Examples include sugar. As the monosaccharide having 4 to 6 carbon atoms, 5-carbon sugar or 6-carbon sugar is preferable. As the 5-carbon sugar, xylose or ribose is preferable. As the 6-carbon sugar, fructose, psicose, sorbose, galactose, fucose, glucose, or rhamnose are preferable. Of these, rhamnose is more preferred. These monosaccharides having 4 to 6 carbon atoms can be used alone or in combination of two or more.

The sugar alcohol having 4 to 6 carbon atoms is not particularly limited as long as it has 4, 5, or 6 carbon atoms. The sugar alcohol may be a chain sugar alcohol or a cyclic sugar alcohol. Further, the sugar alcohol may be a D-form, an L-form, or a mixture of a D-form and an L-form. Examples of sugar alcohols having 4 to 6 carbon atoms include sugar alcohols having 4 carbon atoms such as erythritol and traytoll; sugar alcohols having 5 carbon atoms such as arabinitol, xylitol and ribitol (adonitol); sorbitol, mannitol, etc. Sugar alcohols with 6 carbon atoms such as igitol, galactitol, and inositol (allo-inositol, chiro-inositol, cis-inositol, epi-inositol, myo-inositol, muco-inositol, neo-inositol, scyllo-inositol) are listed. Be done. As the sugar alcohol having 4 to 6 carbon atoms, a sugar alcohol having 4 carbon atoms or a sugar alcohol having 6 carbon atoms is preferable. Erythritol is preferable as the sugar alcohol having 4 carbon atoms. As the sugar alcohol having 6 carbon atoms, sorbitol, mannitol, or inositol (amyo-inositol among inositol) is preferable. These sugar alcohols having 4 to 6 carbon atoms can be used alone or in combination of two or more. Further, a monosaccharide having 4 to 6 carbon atoms and a sugar alcohol having 4 to 6 carbon atoms can be used in combination.

Monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms may be natural products or synthetic products, such as those purified from natural products and those commercially available. , Not particularly limited. Further, the monosaccharide having 4 to 6 carbon atoms and the sugar alcohol itself having 4 to 6 carbon atoms may be used, or a solvate such as a hydrate may be used. Examples of the solvate of rhamnose include L-rhamnose monohydrate manufactured by Sigma. Further, for example, rhamnose refined from a natural product is obtained by fermenting and concentrating and separating glycosides or fats and oils contained in rutin extract, etc., as described in the existing voluntary standards for additives. Can also be used after being hydrolyzed and separated and purified.

Bone metabolism means bone remodeling in which bone formation by osteoblasts and bone resorption by osteoclasts are repeated. In the present invention, improvement of bone metabolism means normalization of bone metabolism biased toward bone resorption due to enhanced differentiation into osteoclasts, as seen in osteoporosis, by suppressing differentiation into osteoclasts. It means to improve the balance. Examples of the bone metabolism improving action include an osteoclast differentiation inhibitory action, a bone component maintaining action, and a bone resorption suppressing action. The present invention may exhibit one or more actions selected from the group consisting of an osteoclast differentiation inhibitory action, a bone component maintenance action, and a bone resorption inhibitory action.

The osteoclast differentiation inhibitory action means an action of suppressing the differentiation of osteoclast precursor cells into osteoclasts. By suppressing the differentiation into osteoclasts, the number of osteoclasts can be reduced, the increase in bone resorption can be suppressed, and the balance of bone metabolism can be maintained appropriately.

Bone component maintenance action is to suppress the decomposition of proteins such as collagen contained in osteoclasts and bone matrix (bone resorption) by suppressing the differentiation into osteoclasts, and the bone matrix and proteins, etc. It means the action of maintaining the bone component of the bone without dissolving it. In bone metabolism that is biased toward bone resorption, the balance of bone metabolism can be maintained properly by maintaining the bone matrix and protein without dissolving them.

The bone resorption inhibitory action means an action of suppressing bone destruction and resorption by acids and proteases secreted by osteoclasts by suppressing differentiation into osteoclasts. In bone metabolism that is biased toward bone resorption, it is possible to maintain an appropriate balance of bone metabolism by suppressing bone resorption by osteoclasts.

By suppressing the differentiation into osteoclasts, the bone metabolism biased to bone resorption is improved to a normal balance by the osteoclast differentiation inhibitory action, the bone component maintenance action, or the bone resorption inhibitory action, and the bone becomes brittle. Or, it is possible to suppress a decrease in bone mass and maintain a strong bone.

As a method of suppressing the proliferation of osteoclasts, a method of inducing cell death of osteoclasts by soy isoflavone is known, and soy isoflavone is an apoptosis-related gene Bim that directly induces apoptosis of osteoclasts. It is thought to induce cell death of osteoclasts by promoting expression (Gakuen / Life Science Bulletin No.794 21-26 2006). However, in consideration of safety and the like, it is preferable to suppress the proliferation of osteoclasts without inducing cell death.

(I) Composition for improving bone metabolism This composition for improving bone metabolism is composed of a group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms as long as they have an effect of improving bone metabolism. It may contain at least one selected. The total content of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms in the composition for improving bone metabolism is not particularly limited as long as it has a bone metabolism improving effect, and is 0. It can be appropriately set from the range of .001 to 100% by mass.

This composition for improving bone metabolism can be used as an additive for imparting a bone metabolism improving effect to foods and drinks or pharmaceuticals. The composition for improving bone metabolism may be in any form, but may be in solid forms such as powder, granules, tablets, and capsules, and semi-syrup, emulsion, liquid, and gel. It can have a solid or liquid form.

Various carriers and additives can be added to the composition for improving bone metabolism in order to prepare the composition into an appropriate form and to stabilize the composition.

Such carriers or additives include monosaccharides (eg glucose, galactose, fructose, etc.), disaccharides (eg, sucrose, sucrose, lactose, starch sugar, trehalose, etc.), sugar alcohols (eg, xylitol, sorbitol, mannit, etc.). Etc.), oligosaccharides, starch (eg, corn starch, partially pregelatinized starch, etc.), starch degradation products (eg, dextrin, powdered candy, etc.), cellulose or cellulose derivatives (eg, crystalline cellulose, low-substituted hydroxypropyl cellulose, carme). Excipients such as loin sodium) and talc; binders such as starch, pregelatinized starch, gelatin, arabic gum, dextrin, methylcellulose, ethylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose or salts thereof. Disintegrants such as calcium carbonate, crospopidone, starch, carboxymethyl cellulose calcium, low-substituted hydroxypropyl cellulose, carboxymethyl starch, crystalline cellulose, agar; lubricants such as magnesium stearate, talc, polyethylene glycol, silicic anhydride; Sustaining agents such as polysolvate 80, polyoxyethylene hydrogenated castor oil, and pluronic; coating agents such as sucrose, talc, precipitated calcium carbonate, gelatin, gum arabic, purulan, carnauba wax, hydroxypropyl methylphthalate; sucrose, starch, sodium saccharin , Sorbitol, starch, and flavoring agents such as aspartame. In addition to the above components, stabilizers, surfactants, plasticizers, capsule coatings, solubilizers, reducing agents, buffers, etc., which are usually accepted as pharmaceutical additives, as long as the effects of the present invention are not impaired. Sweeteners, bases, absorption enhancers, adsorbents, hardeners, antioxidants, brighteners, fragrances, skins, supports, sustainers, wetting agents, wetting regulators, fillers, defoaming agents, Cooling agents, adhesives, enhancers, chewing agents, antistatic agents, fragrances, colorants, sugar coating agents, tonicity agents, softeners, emulsifiers, pressure-sensitive adhesives, pressure-sensitive adhesives, thickeners, pH adjusters, floating Agents, dispersants, propellants, fragrances, rust preventives, moisture proofing agents, release control films, preservatives, trapping agents, preservatives, solubilizers, dissolution aids, solvents, mold release agents, fluidizers, etc. Acceptable as food additives, sweeteners, colorants, preservatives, thickeners, stabilizers, gelling agents, glues, antioxidants, color formers, bleaching agents, antifungal agents, emulsifiers, swelling agents , Seasonings, acidity agents, bitterness agents, brighteners, gum bases, nutritional enhancers, manufacturing agents, and the like, and optional ingredients such as fragrances can be added as desired.

In addition to the above components, the composition for improving bone metabolism can contain any edible component as long as it does not interfere with the effects of the present invention.

Edible ingredients include, for example, excipients, organic acids, colorants, amino acids (eg, glycine, arginine, lysine, alanine, glutamate, histidine, threonine, aspartame, aspartame, phenylalanine, leucine, valine, serine, tyrosine). , Isoleucine, methionine, etc.), nutrients (including vitamins and minerals), antioxidants, preservatives, antibacterial agents, bacteriostatic agents, plant extracts (eg, tea extract, coffee extract, cocoa extract, etc.) , Fruit juice (eg orange, grape, apple, peach, pineapple, tomato, strawberry, etc.), sweetener (sucrose, high fructose corn syrup, lactose, malt sugar, glucose, fructose, converted sugar, water candy, powdered water candy, reduced malt water candy , Sugars such as honey, trehalose, palatinose, D-xylose; sugar alcohols such as xylitol, sorbitol, martitol, erythritol; , Stevia extract (eg, stebioside, etc.), Luo Han Guo extract (eg, mogroside, etc.) and other high-sweetness sweeteners, and fragrances.

A composition for improving bone metabolism, which comprises at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms, is as shown in Examples below. , It is possible to suppress the differentiation into osteoclasts and reduce the number of cells that differentiate into osteoclasts. As described above, by suppressing the differentiation into osteoclasts, the bone metabolism biased toward bone resorption due to the enhanced differentiation into osteoclasts, which is seen in osteoclasts, is improved to a normal balance. Therefore, a composition for improving bone metabolism was added, which comprises at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. Foods and drinks or pharmaceuticals can be used to improve bone metabolism. In addition, foods and drinks to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is added. Alternatively, the drug can be ingested or administered to a subject who has or is suspected of having an abnormal bone metabolism. For example, in the case where bone resorption is promoted as compared with bone formation, or when bone resorption is suspected to be enhanced, the patient may have an abnormal bone metabolism or have an abnormal bone metabolism. It can be judged to be suspected. For example, the state of bone formation in a subject can be evaluated by measuring bone formation markers such as osteocalcin (OC) or bone-type alkaline phosphatase (BAP). In addition, for example, the state of bone resorption in a subject can be evaluated by measuring bone resorption markers such as type I collagen cross-linked N-telopeptide (NTx) and tartrate-resistant acidic phosphatase (TRACP-5b). .. For example, if the measured value of the bone resorption marker is higher than the standard value generally used in the art, it is judged that bone resorption is suspected to be enhanced. Can be done. For NTx, for example, 10.7 to 24.0 nmol BCE (Bone Collagen Equivalent) / L can be used as a reference value as a value measured using serum collected from a postmenopausal woman (bone in osteoporosis treatment). Guide to proper use of metabolic markers, 2018 edition, Japan Osteoporosis Society). For TRACP-5b, for example, 250 to 760 mU / dL can be used as a reference value as a value measured using serum collected from postmenopausal women (Guide to proper use of bone metabolism markers in osteoporosis treatment, 2018). Annual edition, Japan Osteoporosis Society). The reference value can be appropriately set according to the type of sample obtained from the subject (for example, serum, urine, etc.), the age of the subject, and the gender. Further, for example, when the measured value of the bone formation marker is lower than the reference value generally used in the art, it is suspected that bone resorption is enhanced. You can judge. For OC, for example, as a value measured using serum collected from postmenopausal women, 14.2 to 54.8 ng / mL can be used as a reference value (guide to proper use of bone metabolism markers in osteoporosis treatment). , 2018 edition, Japan Osteoporosis Society). For BAP, for example, as a value measured using serum collected from postmenopausal women, 3.8 to 22.6 μg / L can be used as a reference value (guide to proper use of bone metabolism markers in osteoporosis treatment). , 2018 edition, Japan Osteoporosis Society). Further, for example, the degree of bone formation is evaluated by comparing the measured value of the bone formation marker with the reference value generally used in the technical field, and the measured value of the bone resorption marker is generally used in the technical field. Evaluate the degree of bone resorption by comparing with the standard value used in, and compare the degree of bone resorption with the degree of bone resorption, and if the degree of bone resorption is greater than the degree of bone resorption , It can be judged that bone resorption is enhanced. Therefore, foods and drinks to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is added. Or, the drug is, for example, ingested or administered to a subject whose NTx measured using serum is 25, 26, 27, 28, 29, 30, 35, 40, 45, or 50 nmol BCE / L or more. can do. In addition, foods and drinks to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is added. Alternatively, the drug can be ingested or administered, for example, by TRACP-5b measured with serum to a subject of 770, 780, 790, 800, 850, 900, 950, or 1000 mU / dL or higher. .. In addition, foods and drinks to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is added. Alternatively, the drug can be used, for example, in a subject having an OC measured using serum of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 ng / mL or less. It can be ingested or administered. In addition, foods and drinks to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is added. Alternatively, for pharmaceutical products, for example, BAP measured using serum is 0.01, 0.05, 0.1, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0. Alternatively, it can be ingested or administered to a subject of 3.5 μg / L or less. The subject may be, for example, a male, a female, or a postmenopausal female.

Further, in bone resorption diseases such as osteoporosis, the differentiation of osteoclasts is promoted by the differentiation of osteoblasts, and the balance is inclined in the direction of osteolysis. From this, food and drink to which the composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms was added. Goods or medicines can be used for the treatment or prevention of bone resorption disorders. In addition, foods and drinks to which a composition for improving bone metabolism, which comprises at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms, is added. Alternatively, the drug can be ingested or administered to a subject having or suspected of having a bone resorption disorder. Examples of bone resorption diseases include osteoporosis (primary osteoporosis; secondary osteoporosis derived from drugs, lifestyle-related diseases, rheumatism, nephropathy, etc.).

By suppressing the differentiation into osteoclasts, the bone metabolism biased toward bone resorption is improved to a normal balance, and it is possible to suppress the brittleness of bone or the decrease in bone mass. From this, food and drink to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms was added. Goods or medicines can be used to increase bone mass. In addition, foods and drinks to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is added. Alternatively, the drug can be ingested or administered to a subject who has or is suspected of having reduced bone mass. For example, if the young adult comparison% (YAM; Young Adult Mean) is less than 80%, it can be determined that the bone mass is decreased or that the bone mass is suspected to be decreased. A food or drink or a pharmaceutical product to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is added. For example, YAM ingests less than 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, or 40% of subjects. Or can be administered.

In addition, when the bone that supports the teeth (alveolar bone) is promoted to differentiate into osteoclasts, bone metabolism becomes biased toward bone resorption, and alveolar bone resorption occurs, resulting in periodontal disease such as periodontitis. Is known to occur. From this, food and drink to which the composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms was added. Goods or medicines can be used for the treatment or prevention of periodontal disease. In addition, foods and drinks to which a composition for improving bone metabolism containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is added. Alternatively, the drug can be ingested or administered to a subject who has or is suspected of having periodontal disease.

(II) Foods and drinks for improving bone metabolism or pharmaceutical products The foods and drinks or pharmaceutical products for improving bone metabolism of the present invention consist of a group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. A food or drink or a pharmaceutical product containing at least one selected.

The food or drink or pharmaceutical product for improving bone metabolism of the present invention is selected from at least a group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms as long as they have a bone metabolism improving effect. Anything containing one type may be used. The total content of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is not particularly limited as long as it has an effect of improving bone metabolism, and ranges from 0.001 to 100% by mass. It can be set as appropriate.

The target food and drink is not particularly limited, but for example, soft drinks (for example, tea-based drinks, fruit drinks, vegetable drinks, coffee drinks, cocoa drinks, sports drinks, carbonated drinks, dairy drinks, soymilk and soymilk drinks, sports Beverages, etc.), dairy products (eg, milk, lactic acid bacteria beverages, etc.); soybeans, miso soup, soup powder, sweet sake, and other juices; confectionery (paste and gel-like confectionery, and confectionery prepared in fluid form Includes mixer foods, paste foods, and soy milk foods]; Dietary supplement foods and drinks (paste and gel food supplement foods and foods prepared in fluid form [mixer foods, paste foods, and soy milk foods] ]; Main foods (for example, rice foods, noodles, breads, etc., which are prepared in a fluid state [mixer foods, paste foods, and baby foods]) and delicatessen (prepared delicatessen in a fluid state) (Including mixer foods, paste foods, and soymilk foods); concentrated liquid foods; enteric nutritional supplements (orally administered or orally ingested) and the like. Beverages are particularly preferred.

The target pharmaceutical products may be those administered orally, for example, powders (powder), granules, tablets (including troches and chewables), pills, capsules, films, and liquids (including pills, capsules, films, and liquids). Drinks) and the like.

The amount of the food or drink for improving bone metabolism or the amount of the pharmaceutical product of the present invention may be appropriately set according to the condition of the subject to be administered or ingested. The administration or ingestion can be divided into, for example, several times a day (preferably 1, 2, or 3 times).

According to the present invention, it is used for improving bone metabolism by containing at least one selected from the group consisting of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms. , Food and drink, or pharmaceuticals can be manufactured.

(III) Method for imparting bone metabolism improving action The method for imparting the bone metabolism improving action of the present invention comprises a monosaccharide having 4 to 6 carbon atoms and a monosaccharide having 4 to 6 carbon atoms in the food or drink or drug targeted in (II) above. It can be carried out by adding at least one selected from the group consisting of sugar alcohols having 4 to 6 carbon atoms. The total content of monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms is not particularly limited as long as it has an effect of improving bone metabolism, and ranges from 0.001 to 100% by mass. It can be set as appropriate. In addition, monosaccharides having 4 to 6 carbon atoms and sugar alcohols having 4 to 6 carbon atoms can be added at any stage in the manufacturing process of foods and drinks or pharmaceutical products.

The contents of the present invention will be specifically described with reference to the following experimental examples and examples. However, the present invention is not limited thereto. In the following, the experiments are carried out under atmospheric pressure and normal temperature conditions, unless otherwise specified. Also, unless otherwise specified, "%" means "mass%".

Experimental Example 1
(Effect confirmation test on osteoclast differentiation 1)
The following tests were performed to confirm the effect on osteoclast differentiation.

As the cells, RAW 264, which is an osteoclast precursor cell transferred from RIKEN, was used. RANKL 264 is added to α-MEM medium (containing 100 IU / mL penicillin, 100 mg / mL ligand mycin) containing 10% (v / v) of fetal bovine serum (FBS) as a differentiation inducer in 500 ng / mL Receptor activator of nuclar factor. The cells supplemented with kappa-β ligand (RANKL) were used and cultured at 37 ° C. in the presence of 5% CO ₂ . Culture was started by inoculating 100 μl of the plate on a 96-well plate so as to have 5 × 10 ³ cells / well. The addition of rhamnose was started immediately after sowing, the medium was exchanged on the 4th day, and the cells were cultured for a total of 7 days. Rhamnose was dissolved in sterile water to a final concentration of 1.5, 15, 150, 250, 500 μM, and added to a concentration of 1% (v / v) with respect to the medium. Similarly, the test was conducted with glucose having a final concentration of 150 μM and fucose.

Tartrate-resistant acidic phosphatase (TRAP) staining and measurement of activity were performed on these as indicators of osteoclast differentiation. TRAP staining was tested using a TRAP staining kit manufactured by Cosmo Bio Co., Ltd. Specifically, the culture solution was withdrawn, the cells were washed once with 100 μL / well PBS, and 50 μL / well of a 10% (v / v) formalin solution was added in advance to fix the cells. Then, it was allowed to stand at room temperature for 5 minutes, and washed 3 times with 250 μL / well of purified water. 50 μL / well of the color-developing reagent was added, and the mixture was allowed to stand in a constant temperature bath at 37 ° C. for 1 hour. Then, it was washed once with 250 μL / well of purified water, and the number of cells was counted. The results are shown in FIG.

As can be seen from this result, rhamnose, fucose, and glucose were found to suppress the differentiation into osteoclasts. In particular, it was found that the addition of ramnose suppressed the differentiation into osteoclasts, and the number of cells differentiated into osteoclasts was significantly reduced in the concentration of 150 μM or more.

Experimental Example 2
(Osteoclast toxic effect confirmation test 1)
The following test (growth assay) was performed to confirm the toxic effects of osteoclasts.

As the cells, RAW 264, which is an osteoclast precursor cell transferred from RIKEN, was used. RAW 264 was cultured in α-MEM medium (containing 100 IU / mL penicillin, 100 mg / mL streptomycin) containing 10% (v / v) of fetal bovine serum (FBS) at 37 ° C. in the presence of 5% CO ₂ . Culture was started by inoculating 100 μl of the plate on a 96-well plate so as to have 5 × 10 ³ cells / well. The addition of rhamnose was started immediately after sowing, the medium was exchanged on the 4th day, and the cells were cultured for a total of 7 days. Rhamnose was dissolved in sterile water to a final concentration of 15, 150, 500 μM, fucose to a final concentration of 150 μM, and glucose to a final concentration of 15, 150, 500 μM, and 1 μl was added to the medium.

After culturing, add 10 μl of MTT [3- (4,5-Dimethylthial-2-yl) -2,5-Diphenyltellazalium Bromide] diluted with phosphate buffered saline (PBS) to 5 mg / ml. Then, it was allowed to stand at 37 ° C. in the presence of 5% CO ₂ for 4 hours. Then, 10 μl of an MTT solution prepared to have 10 mass% sodium uralyl sulfate and 0.01 N hydrochloric acid was added to the wells. MTT is converted to insoluble formazan by reductase in living cells, and formazan is solubilized by this lysate. It was shielded from light with aluminum foil and left at room temperature overnight. The next day, the absorbance at 571 nm was measured with a plate reader. The results are shown in FIG.

As can be seen from this result, it was found that the addition of rhamnose, fucose, or glucose did not induce cell death of osteoclasts. That is, rhamnose and the like are highly safe materials because they can suppress the differentiation into osteoclasts without inducing cell death of osteoclasts like soy isoflavone.

Experimental Example 3
(Effect confirmation test 2 on osteoclast differentiation)
In addition to rhamnose, tests were performed in the same manner as in Example 1 using xylose, ribose, fructose, galactose, erythritol, sorbitol, mannitol, inositol, psicose, and sorbose. In each case, each was dissolved in sterilized water so that the final concentration was 150 μM, and added so as to have a concentration of 1% (v / v) with respect to the medium. In addition, soy isoflavone was added so as to have a final concentration of 92 μM, which was used as a positive control. The results are shown in FIG.

As can be seen from this result, by adding a monosaccharide having 4 to 6 carbon atoms or a sugar alcohol having 4 to 6 carbon atoms, the differentiation into osteoclasts is suppressed and the cells differentiate into osteoclasts. It turned out that the number decreased. Among monosaccharides having 4 to 6 carbon atoms or sugar alcohols having 4 to 6 carbon atoms, it was found that the number of cells differentiated into osteoclasts was significantly reduced, especially when rhamnose was used.

Experimental Example 4
(Osteoclast toxic effect confirmation test 2)
In addition to rhamnose, xylose, ribose, fructose, galactose, erythritol, sorbitol, mannitol, inositol, psicose, and sorbose were used in the same test as in Example 2. In each case, each was dissolved in sterilized water so that the final concentration was 150 μM, and 1 μl was added to the medium. The results are shown in FIG.

As can be seen from this result, it was found that the addition of a monosaccharide having 4 to 6 carbon atoms or a sugar alcohol having 4 to 6 carbon atoms did not induce cell death of osteoclasts. That is, a monosaccharide having 4 to 6 carbon atoms or a sugar alcohol having 4 to 6 carbon atoms can suppress the differentiation into osteoclasts without inducing cell death of osteoclasts like soy isoflavone. Therefore, it is a highly safe material.

Claims (8)

A composition for improving bone metabolism containing at least one selected from the group consisting of rhamnose and fucose . The composition for improving bone metabolism according to claim 1, wherein the improvement of bone metabolism is due to one or more actions selected from the group consisting of an osteoclast differentiation inhibitory action, a bone component maintenance action, and a bone resorption inhibitory action. .. A food or drink for improving bone metabolism, or a pharmaceutical product, which comprises at least one selected from the group consisting of rhamnose and fucose . The food or drink for improving bone metabolism according to claim 3, wherein the improvement of bone metabolism is due to one or more actions selected from the group consisting of an osteoclast differentiation inhibitory action, a bone component maintenance action, and a bone resorption inhibitory action. Or medicine. The food or drink for improving bone metabolism or a pharmaceutical product according to claim 3 or 4, which is a composition for treating or preventing a bone resorption disease. The food or drink for improving bone metabolism or a pharmaceutical product according to any one of claims 3 to 5, which is a composition for increasing bone mass. A method for imparting a bone metabolism improving effect to a food or drink or a drug, which comprises adding at least one selected from the group consisting of rhamnose and fucose to the food or drug. The method according to claim 7, wherein the bone metabolism improving action is one or more actions selected from the group consisting of an osteoclast differentiation inhibitory action, a bone component maintaining action, and a bone resorption suppressing action.

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