JP2019122411A - Bone fortifier dietary supplements - Google Patents

Abstract

To provide bone fortifier dietary supplements with a high osteogenesis promoting effect.SOLUTION: A bone fortifier dietary supplement is characterized by containing as an active ingredient isoflavone, and specific components of plant materials, such as Hordeum vulgare, Ipomoea batatas, Peucedanum japonicum, Pinus, Terminalia, Cocos nucifera, Aristotelia Chilensis, and Brassica oleracea.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a bone strengthening agent, and more particularly to a bone strengthening agent comprising isoflavone and certain other components as active ingredients.

  In recent years, osteoporosis has tended to increase mainly in elderly women. This osteoporosis is said to be caused by deterioration of calcium absorption from the intestine and decrease in secretion of female hormones with age.

  On the other hand, soy isoflavone, as also called phytoestrogen, has an estrogen-like action of female hormones and is known to promote bone formation and suppress bone resorption (bone destruction) .

  As a preparation using such a soy isoflavone, for example, a preparation for preventing periodontal disease characterized by containing soy isoflavone aglycone (see Patent Document 1), a fermented plant extract and isoflavone are characterized. A plant fortifying agent comprising a fermented plant extract composition (see Patent Document 2), a milk-derived basic protein fraction and / or a milk-derived basic protein fraction and a soy isoflavone as active ingredients Reference 3) has been proposed.

JP 2002-121146 A JP 2012-240946 A JP, 2013-184959, A

  An object of the present invention is to provide a bone strengthening agent having a high bone formation promoting effect.

  The present inventors have intensively investigated and studied the bone strengthening ability of isoflavones, and found that by combining isoflavones with certain other components, it is possible to obtain a high bone formation promoting effect, and to complete the present invention. It reached. That is, it has been found that the ability to promote bone formation can be synergistically improved by combining isoflavone with a specific other component that has little or no ability to promote bone formation.

That is, the present invention relates to a bone strengthening agent characterized by containing isoflavone and at least one component selected from the group consisting of the following (a) to (e) as an active ingredient.
(A) at least one plant material selected from barley, sweet potato, long-lived grass, pine, terminaria, coconut, makiberry and kale (b) at least one additive selected from reduced maltose and calcium stearate (c) asparagine And at least one amino acid selected from cysteine, glutamine, glutamic acid, glycine, leucine, lysine, phenylalanine, serine and valine (d) polyphenol consisting of chlorogenic acid (e) vitamin B1, vitamin B2, vitamin B6, vitamin B12, At least one vitamin mineral selected from sodium pantothenate, niacin, folic acid, vitamin K, magnesium, iron, selenium and calcium.

  The bone strengthening agent of the present invention may be obtained by adding an active ingredient comprising isoflavone and at least one component selected from the group consisting of (a) to (e).

In the bone strengthening agent of the present invention, the blending mass ratio of isoflavone and other active ingredients is preferably in the range of 0.5: 1 to 70: 1.
Also, the bone strengthening agent of the present invention is preferably a tablet, a capsule, a powder, a granule or a solution.

  The present invention also relates to a method for bone strengthening (except for medical practice), which comprises taking the bone strengthening agent of the present invention.

  According to the bone strengthening agent of the present invention, a high bone formation promoting effect can be obtained, and bone can be strengthened.

It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + plant material) of this invention to an osteoblast cell line (MC3T3-E1), Barley, sweet potato, longevity as a plant material sequentially from the left The case of using grass and pine is shown. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + plant material) of this invention to an osteoblast cell line (MC3T3-E1), and it is a terminal material as a plant material Shows the case of using. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + additive) of this invention to an osteoblast cell line (MC3T3-E1). The left graph uses reduced maltose as an additive, and the right graph uses calcium stearate as an additive. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + amino acid) of this invention to an osteoblast cell line (MC3T3-E1). The left graph uses asparagine as the amino acid and the right graph uses cysteine as the amino acid. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + amino acid) of this invention to an osteoblast cell line (MC3T3-E1). The left graph uses glutamine as the amino acid, and the right graph uses glutamic acid as the amino acid. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + amino acid) of this invention to an osteoblast cell line (MC3T3-E1). The left graph uses glycine as the amino acid, and the right graph uses leucine as the amino acid. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + amino acid) of this invention to an osteoblast cell line (MC3T3-E1). The left graph uses lysine-hydrochloride as the amino acid, and the right graph uses phenylalanine as the amino acid. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + amino acid) of this invention to an osteoblast cell line (MC3T3-E1). The left graph uses serine as an amino acid, and the right graph uses valine as an amino acid. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + polyphenol) of this invention to an osteoblast cell line (MC3T3-E1), and is a thing using chlorogenic acid as polyphenol. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + vitamin * minerals) of this invention to an osteoblast cell line (MC3T3-E1). The graph on the left uses vitamin B1 as a vitamin, and the graph on the right uses vitamin B2 as a vitamin. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + vitamin * minerals) of this invention to an osteoblast cell line (MC3T3-E1). The graph on the left uses vitamin B6 as the vitamins, and the graph on the right uses vitamin B12 as the vitamins. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + vitamin * minerals) of this invention to an osteoblast cell line (MC3T3-E1). The left graph uses sodium pantothenate as the vitamins, and the right graph uses niacin as the vitamins. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + vitamin * minerals) of this invention to an osteoblast cell line (MC3T3-E1). The left graph uses folic acid as a vitamin, and the right graph uses vitamin K as a vitamin. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + vitamins and minerals) of this invention to an osteoblast cell line (MC3T3-E1), and magnesium, iron as minerals in order from the left. The case where serine is used is shown. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + vitamins and minerals) of this invention to an osteoblast cell line (MC3T3-E1), eggshell calcium as minerals, in order from the left. The case where seaweed calcium and fish calcium are used is shown. It is a figure which shows the result of Runx2 gene expression at the time of applying the bone strengthening agent (isoflavone + kale) of this invention to an osteoblast cell line (MC3T3-E1).

  The bone strengthening agent of the present invention is characterized by containing isoflavones and at least one component (hereinafter sometimes referred to as another component) selected from the group consisting of the following (a) to (e) as active ingredients: I assume. The bone strengthening agent of the present invention has a high ability to promote bone formation, and by increasing bone mass, it can strengthen bone and thus prevent or treat osteoporosis.

[Isoflavone]
Isoflavones, which are the active ingredient of the bone strengthening agent of the present invention, are flavonoid compounds that are abundant in leguminous plants, particularly soybeans, and soybean isoflavones derived from soybeans are preferred as isoflavones in the present invention. The isoflavone may be an aglycone or a glycoside. Also, the isoflavone may be purified, but may be a mixture of the raw material (for example, soybean) with other components. Soy isoflavones are commercially available and commercially available products can be used.

[Other ingredients]

(A) Plant Material In the bone strengthening agent of the present invention, at least one plant material selected from barley, sweet potato, long-lived grass, pine, terminaria, coconut, maciberry, and kale as an active ingredient is used together with isoflavone. Is preferred.

  These plant materials may be any part of plants such as leaves, stems, roots, flowers, fruits, stems, branches, etc. In addition to plant materials themselves (including dried matter), crushed materials thereof, squeezed juice And processed materials of plant materials such as extracts. As a ground material, powder, granules and the like can be mentioned. The juice or extract may be liquid, but can also be used as a paste or dry powder. The extract can be obtained by extraction using a suitable solvent, and as the solvent, for example, water (hot water), ethanol, hydrous ethanol can be used. As these plant materials, those commercially available can be used.

  As barley, two-row barley, six-row barley, etc. can be used. As a site | part used as a plant raw material of this invention, a stalk and a leaf are preferable, and a young leaf is especially preferable.

  Sweet potato is a plant belonging to the family Convolvulaceae, and is generally called sweet potato. The varieties of sweet potato are not particularly limited, and examples thereof include: sweet potato, joy white, koganene sengan, shiro yutaka, satu mustache, and ayamurasaki. As a site | part used as a plant raw material of this invention, a stalk and a leaf are preferable, and a young leaf is especially preferable.

  Long-lived grass is a perennial plant also known as rickets that belongs to the genus Seriaceae. As a site | part used as a plant material of this invention, a leaf and a root are preferable.

  As pines, for example, French coast pine (Pinus Martima), larch, Japanese red pine, red pine, etc. can be mentioned, and among these, French coast pine (Pinus Martima) rich in proanthocyanidins is preferable. As a site | part used as a plant raw material of this invention, bark is preferable, and the extract obtained from this pine bark is especially preferable. The extract contains, in addition to proanthocyanidins, a high concentration of oligomeric proanthocyanidins, and preferably contains, for example, 20% by mass or more of oligomeric proanthocyanidins based on the dry mass of the extract.

  Examples of terminalia can include Terminalia bellirica (belerica), Terminalia catappa, Terminali tomentosa, Terminalia citrina, Terminalia phellocarpa, Terminalia copelandii, Terminalia brassi, Terminalia ivorensis, Terminalia superba, Terminalia arjuna, Terminalia chebula and the like. Among them, Terminalia bellirica (belerica) and Terminalia chebula are preferable. As a site | part used as a plant material of this invention, a fruit is preferable.

  Coconut is a palm family plant, and as a part used as a plant material of the present invention, a fruit (endosperm) is preferable.

  Makiberry is a plant of the Polantoaceae family, originating in Patagonia, Chile, and its scientific name is Aristotellia chilensis. As a site | part used as a plant material of this invention, a fruit is preferable.

  Kale is a cruciferous plant, and as a part used as a plant material of the present invention, a leaf and a stem are preferable. Specifically, a kale dried and crushed, a kale slurry or squeezed solution dried and powdered, and an extract obtained from kale or its dried material are preferable. In particular, it is preferable that the kale be subjected to processing such as drying and extraction immediately after harvesting. If time is required for the treatment, storage is preferably performed by storage means commonly used by those skilled in the art, such as low temperature storage, to prevent deterioration of the kale. The kind of kale is not particularly limited, and various kinds of kale such as kitchen kale, tree kale, bush kale, mallow kale, collard green leaves, and the like may be used.

(B) Additives In the bone strengthening agent of the present invention, it is preferable to use at least one additive selected from reduced maltose and calcium stearate as an active ingredient together with isoflavone. Reduced maltose and calcium stearate are additives used in the production of tablets and the like, and reduced maltose is usually used as an excipient, and calcium stearate is usually used as a lubricant.

(C) Amino Acid In the bone strengthening agent of the present invention, at least one amino acid (salt) selected from asparagine, cysteine, glutamine, glutamic acid, glycine, leucine, lysine, phenylalanine, serine and valine as active ingredients together with isoflavone Is preferably used). As a salt, sodium salt, hydrochloride etc. can be mentioned, for example.

(D) Polyphenol In the bone strengthening agent of the present invention, it is preferable to use a polyphenol consisting of chlorogenic acid as an active ingredient together with isoflavone.

(E) Vitamins and minerals In the bone strengthening agent of the present invention, vitamin B1, vitamin B2, vitamin B6, vitamin B12, sodium pantothenate, niacin, folic acid, vitamin K, magnesium, iron, as an active ingredient, together with isoflavone. It is preferable to use at least one vitamin and mineral selected from selenium and calcium. In addition, iron, selenium, magnesium, and calcium as minerals of this invention include the form of the compound containing these metals.

  The bone strengthening agent of the present invention is not particularly limited as long as it can be distinguished from other products as a product in that it contains isoflavone and a predetermined other component and is used for bone strengthening, for example It is included in the scope of the present invention that any of the main body of the product according to the present invention, the package, the manual, and the advertising material has the effect that the bone strengthening function (bone formation promoting function) is present. For example, so-called health food such as pharmaceuticals (including quasi-drugs), functional health food such as food for specified health use, nutritive function food, functional display food, etc. and indication of efficacy is recognized from specified organizations, feed etc. Can be mentioned. In the so-called health food, it is possible to exemplify those displaying "for maintaining bone health", "for those concerned about bone health", "for preventing bone becoming brittle" and the like.

  The form of the bone strengthening agent of the present invention is, for example, tablets, capsules, powders, granules, solutions, granules, bars, plates, blocks, solids, rounds, pastes Agents, creams, caplets, gels, chewables, sticks and the like. Among these, the forms of tablets, capsules, powders, granules and solutions are particularly preferable. Specifically, container-packed beverages filled in plastic bottles, cans, bottles, etc., instant powder beverages for dissolving in water (hot water), milk, fruit juice, green juice, etc. for drinking and instant granular beverages are exemplified. be able to. These are preferable in that they are easy to drink easily at the time of eating and the like and that their palatability can be enhanced.

  As content of isoflavone and other ingredients (active ingredient) in a bone strengthening agent of the present invention, it may be contained suitably in the range which the effect plays.

  Generally, when the bone strengthening agent of the present invention is a pharmaceutical product or a supplement (tablet, capsule), it is preferable that the active ingredient be contained in an amount of 0.01 to 100% by mass in terms of dry mass, The content is more preferably 0.1 to 85% by mass, and further preferably 0.5 to 70% by mass.

  When the bone strengthening agent of the present invention is a container-packed beverage (liquid preparation), the active ingredient is preferably contained in an amount of 0.01 to 15% by mass in terms of dry mass, preferably 0.03 to 12.5. It is more preferable that it is contained by mass%, and it is further preferable that it is contained by 0.05 to 10 mass%.

  When the bone strengthening agent of the present invention is an instant powdery beverage (powder) or an instant granular beverage (granular), the active ingredient is contained in an amount of 0.1 to 80% by mass in terms of dry mass. It is preferable that it is contained, 0.5 to 70 mass% is more preferable, and 1 to 60 mass% is further preferable.

  In order to exert the effects of the present invention more effectively, the active ingredient is preferably contained 80% or more, preferably 90% or more, of the whole of the bone strengthening agent of the present invention (excluding water) in dry mass conversion. Is more preferably contained, more preferably 95% or more, and particularly preferably 100%. Furthermore, when the bone strengthening agent of the present invention contains any of the components (a) to (e), it is preferable that the contained component is composed of only the active ingredient in the present invention. That is, when the bone strengthening agent of the present invention contains, for example, the component (a) (plant material), it is configured not to contain plant materials other than barley, sweet potato, long-lived grass, pine, terminaria, coconut, maciberry, kale It is preferable to do.

  The intake amount of the bone strengthening agent of the present invention is not particularly limited, but from the viewpoint of exerting the effects of the present invention more remarkably, the intake amount of the active ingredient per day is 0.1 mg / day or more. It is preferable to ingest it, more preferably 1 mg / day or more, and even more preferably 10 mg / day or more. The upper limit is not particularly limited, and is, for example, 8 g / day, preferably 4 g / day. Moreover, it is preferable to ingest so that the intake of isoflavone by the bone strengthening agent intake of this invention may be 30 mg / day or less (in terms of aglycone).

  The bone strengthening agent of the present invention can be divided into one container or, for example, into a plurality of containers of 2 to 3 and stored for one day so that the daily intake can be the intake.

  The blending mass ratio of isoflavone and other components is preferably in the range of 0.5: 1 to 70: 1, more preferably in the range of 0.75: 1 to 60: 1, in terms of dry mass. The range of 1: 1 to 60: 1 is more preferable, and the range of 1: 1 to 50: 1 is particularly preferable. When the blend ratio of isoflavone and other components is in the above range, the effects of the present invention can be more effectively exhibited.

  The bone strengthening agent of the present invention can be produced by a known formulation method, if necessary, by adding components other than the orally acceptable active ingredient.

  Moreover, as the bone strengthening agent of the present invention, in addition to the bone strengthening food containing an active ingredient, a bone strengthening food obtained by adding the active ingredient to a food can be mentioned, for example, The thing which added the active ingredient to the foodstuff which does not usually contain an active ingredient can be mentioned. In addition of the active ingredient, each ingredient may be added separately, may be added simultaneously, and may be added with other ingredients other than the active ingredient.

  The bone-reinforcing food of the present invention includes, for example, carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages, smoothies, beverages such as green juice; ice cream, ice sherbet, frozen ice such as shaved ice; buckwheat noodles, noodles, Chinese cabbage, Chinese food Noodles, instant noodles and other noodles; candy, candies, gums, chocolate, confections, snacks, biscuits, jellies, jams, creams, baked confections, breads and other confectionery products; Dairy products such as processed milk, fermented milk, yogurt, etc .; Fats and oils such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressings and their processed foods; Seasonings such as sauces, soy sauce; Curry, stew, oyakodon , Rice porridge, risotto, Chinese rice bowl, dried bonito, prawn, beef bowl, Hayashi rice, omelet rice, Oden rice, Obodon, Marobode , Mention may be made of dumplings, Shumai, hamburger, meatballs, various sources, retort pouch foods such as various soups and the like.

  The bone strengthening method of the present invention is characterized by taking the bone strengthening agent of the present invention described above, but does not include medical practice. Examples of the method of the present invention include a method of strengthening bones by providing the food for bone strengthening of the present invention in a restaurant such as a restaurant.

Hereinafter, the present invention will be described based on examples.
Example 1
An osteoblast cell line (MC3T3-E1) cultured in a culture medium (MEMa; Alpha modification of Eagle's Minimum Essential Media, 10% FBS, 1% PS) was seeded to a 96 well plate in an amount of 5 × 10 ³ / well. .

  After that, add 0.1 mL of 0.5 μg / mL isoflavone or a solution in which other components shown in Tables 1 to 5 are dissolved to a predetermined concentration, and culture for 48 hours, and runx2 gene expression to real-time PCR (It was previously confirmed in WST that the concentration at which 90% or more of the cells survive compared to the control). The Runx2 gene is a transcription factor essential for osteoblast differentiation, and is known to induce osteoblast differentiation and promote bone formation.

  The results are shown in Tables 1 to 5 and FIGS. 1 to 15. From left to right, each graph in the figure is "control-(no addition)", "control + (0.5 μg / mL isoflavone alone addition)", "only addition of other components", "0.5 μg / mL isoflavone It represents the result of + addition of other components. Also, the numerical values in the lower part of the graph indicate sample concentrations, and for example, “250-” of barley in FIG. 1 graph indicates barley 250 (μg / mL). The concentration unit of the additive component is μg / mL in all graphs. The graph is expressed as a relative value when the value of control + is 1.

For barley, dried and ground powder of young leaves was used.
For sweet potato, dried and ground powder of young leaves was used.
For long-lived plants, dried and pulverized leaves were used.
For pine, a hot water extract (dry powder) of the bark of French coast pine was used.
For Terminaria, a hot water extract of the fruit (dry powder) was used.
About coconut, after drying commercially available coconut milk, what remove | eliminated oil was used.
As for makiberry, a dried powder of commercially available fruit was used.
For the kale, dried and pulverized leaves were used.
As for Yomogi, finely ground powder of fresh leaves was used.

  As shown in Tables 1 to 5 and FIGS. 1 to 15, the expression level of Runx2 gene in the osteoblast cell line was synergistically increased by combining isoflavone and the other specific component of the present invention. Therefore, according to the bone strengthening agent of the present invention, bone formation can be promoted and bone can be effectively reinforced.

[Example 2] (Production of tablets)
Soy isoflavone 25 mg, aspartame 10 mg, reduced maltose 50 mg, calcium stearate 200 mg, cysteine 10 mg, lysine-hydrochloride 5 mg, phenylalanine 5 mg, serine 0.1 mg, niacin 5 mg, folic acid 0.05 mg, vitamin K 0.1 mg, iron 0.01 mg A mixture consisting of 0.02 mg of magnesium, 50 mg of maki berry, 0.2 mg of pine bark extract and 50 mg of fish calcium was compressed into tablets.

[Example 3] (Manufacture of capsule)
Soy isoflavone 50 mg, aspartame 180 mg, reduced maltose 50 mg, calcium stearate 350 mg, cysteine 10 mg, lysine-hydrochloride 5 mg, phenylalanine 5 mg, serine 0.1 mg, niacin 5 mg, folic acid 0.05 mg, vitamin K 0.1 mg, iron 0.01 mg A mixture consisting of 0.02 magnesium, 50 mg coconut and 0.2 mg seaweed calcium was enclosed in a soft capsule to produce a capsule.

[Example 4] (Production of instant powder 1)
Soy isoflavone 50 mg, aspartame 180 mg, reduced maltose 200 mg, maltose 200 mg, calcium stearate 200 mg, asparagine 250 mg, glutamine 25 mg, glutamine 25 mg, glycine 20 mg, leucine 20 mg, chlorogenic acid 10 mg, vitamin B1 0.1 mg, vitamin B2 0.1 mg, vitamin B6 0.1 mg, vitamin B12 0.05 mg, sodium pantothenate 0.05 mg, folic acid 0.2 mg, vitamin K 0.1 mg, indigestible dextrin 2000 mg, barley young leaf powder 2000 mg, kale powder 2000 mg, sencha finely ground powder 500 mg, 250 mg of shellfish calcium was mixed to produce a powder. When this powder was dissolved in 100 ml of water, it had good solubility.

[Example 5] (Production of instant powder 2)
Soy isoflavone 100 mg, reduced maltose 1000 mg, maltose 1200 mg, sugar 300 mg, indigestible dextrin 2000 mg, asparagine 250 mg, glutamine 25 mg, glycine 20 mg, leucine 20 mg, chlorogenic acid 10 mg, vitamin B1 0.1 mg, vitamin B2 0.1 mg , Vitamin B6 0.1 mg, vitamin B 12 0.05 mg, sodium pantothenate 0.05 mg, folic acid 0.2 mg, vitamin K 0.1 mg, sweet potato young leaf powder 2000 mg, kale powder 2000 mg, sencha finely ground powder 500 mg, coral uncalcined calcium 10 mg was mixed to produce a powder.
When this powder was dissolved in 200 ml of water, it had good solubility.

[Example 6] (Production of PET Bottle Liquid)
Soy isoflavone 75 mg, reduced maltose 2500 mg, asparagine 350 mg, glutamine 50 mg, glutamate 50 mg, glycine 50 mg, leucine 20 mg, valine 20 mg, vitamin B1 0.2 mg, vitamin B2 0.2 mg, vitamin B6 0.2 mg, vitamin B12 0.2 mg, sodium pantothenate 0.1 mg, folic acid 0.2 mg, vitamin K 0.1 mg, barley young leaf powder 2500 mg, sweet potato young leaf powder 2500 mg, long-lived herb 1000 mg, pine bark extract 50 mg, terminalia berylica 250 mg, coral unbaked The solution was prepared by filling 500 mg of calcium and 500 ml of water in a plastic bottle and sealing it.

  The bone strengthening agent of the present invention has an effect of strengthening bone and can be used as an oral preparation, so the industrial usefulness of the present invention is high.

Claims (1)

A food for bone strengthening comprising isoflavone and at least one component selected from the group consisting of the following (a):
(A) lysine, selenium, cysteine, glutamic acid, leucine, valine, long-lived grass, pine

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