JP2023073564A - Bone strengthening agent and bone strengthening composition - Google Patents

Abstract

To provide a bone strengthening agent and a bone strengthening composition that have excellent bone strengthening action and are highly safe.SOLUTION: A bone strengthening agent comprises an ingredient selected from the group consisting of polymethoxyflavone, corosolic acid, pteryxin, dihydro-5,6-dehydrokawain, black ginger extract, Daucus carota subsp. sativus extract, Peucedanum japonicum extract, Gymnema sylvestre extract, Nelumbo nucifera Gaertn. germ extract, Averrhoa carambola leaf extract, and Alpinia speciosa leaf extract, and combinations of two or more of them. There is also provided a bone strengthening composition comprising the bone strengthening agent.SELECTED DRAWING: None

Description

The present invention relates to a bone strengthening agent and a bone strengthening composition.

In recent years, as the population ages, bone-related diseases such as osteoporosis have increased, and strengthening bones has attracted attention in order to live a healthy life.

Remineralization of calcium, which maintains bone strength, is known for strengthening bones. In addition to remineralization, it is also known that reinforcement of collagen fibers, which serve as a skeleton and are responsible for flexibility, is also necessary.

It is also considered effective to promote bone formation by osteoblasts from a young age to increase the bone mass in the body as much as possible and increase the maximum bone mass. That is, it is also important to activate osteoblasts, which are the origin of bones.

Various techniques such as bone strengthening compositions containing peptides that inhibit bone resorption by osteoclasts (see, for example, Patent Document 1) have been proposed as techniques for strengthening bones.

However, there is still strong demand for new materials that have a bone-strengthening effect, are highly safe, and can be widely used as ingredients in foods, beverages, cosmetics, research reagents, etc., and prompt development is required. It is the current situation.

JP 2020-176069 A

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned conventional problems and to achieve the following objects. That is, an object of the present invention is to provide a bone strengthening agent and a bone strengthening composition that have excellent bone strengthening action and are highly safe.

As a result of intensive studies by the present inventors in order to solve the above problems, polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrokawaine, black ginger extract, ginseng extract, and Chomeisou Extracts, gymnema extracts, lotus germ extracts, star fruit leaf extracts, and shell ginger leaf extracts have excellent bone-strengthening effects, are highly safe, and are useful for bone strengthening. , completed the present invention.

The present invention is based on the findings of the present inventors, and means for solving the above problems are as follows. Namely
<1> Polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrokawaine, black ginger extract, ginseng extract, long-life herb extract, gymnema extract, lotus germ extract, star fruit leaf extract A bone strengthening agent characterized by containing either one selected from the group consisting of a substance, shell ginger leaf extract, and a combination of two or more thereof.
<2> The bone strengthening agent according to <1> above, which has at least one of an action of promoting type I collagen production in osteoblasts and an action of activating osteoblasts.
<3> A bone strengthening composition comprising the bone strengthening agent according to any one of <1> to <2>.

INDUSTRIAL APPLICABILITY According to the bone strengthening agent and bone strengthening composition of the present invention, a bone strengthening agent that solves the above-mentioned conventional problems, achieves the above objects, has an excellent bone strengthening effect, and is highly safe. and bone strengthening compositions can be provided.

(bone strengthening agent)
The bone strengthening agent of the present invention includes polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrocawaine, black ginger extract, ginseng extract, long-lived grass extract, gymnema extract, and lotus germ extract. , star fruit leaf extract, shell ginger leaf extract, and a combination of two or more thereof as an active ingredient, and optionally other ingredients.
The active ingredients may be used singly or in combination of two or more.

The above polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrocawain, black ginger extract, western carrot extract, Chomei grass extract, gymnema extract, lotus germ extract, star fruit leaf extract, and shell ginger leaf extract, as well as combinations of two or more thereof, have such excellent effects and are useful as bone strengthening agents. This is new knowledge by the present inventors.

<Black ginger extract>
The black ginger (scientific name: Kaempferia parviflora) is a plant belonging to the genus Zingiberaceae, Zingiberaceae, distributed in Southeast Asia such as Thailand, and easily available from these regions.

The black ginger extract may be prepared from the extraction site used as the raw material for extraction, or may be a commercially available product.

-extracted part-
The extraction part of the black ginger is not particularly limited and can be appropriately selected according to the purpose. and the like. These may be used individually by 1 type, and may use 2 or more types together. Among these, underground parts such as roots and rhizomes are preferable.
The shape, structure, and size of the raw material for extraction of black ginger are not particularly limited, and can be appropriately selected according to the purpose.

-Preparation method of extraction site-
The method for preparing the extracted part of the black ginger is not particularly limited, and can be appropriately selected according to the purpose. be done. The dried product can be subjected to solvent extraction as it is or pulverized. The drying may be performed in the sun, or may be performed using a commonly used dryer.

-extract-
The black ginger extract can be easily obtained by a method commonly used for plant extraction. The form of the black ginger extract is not particularly limited and can be appropriately selected according to the purpose. Purified products, purified products, and the like can be mentioned.

The extraction method is not particularly limited and can be appropriately selected depending on the intended purpose. For example, the extraction part of the black ginger, which is the raw material for extraction, is put into a treatment tank filled with an extraction solvent, and if necessary, while stirring appropriately, for example, the soluble component is eluted by standing still for 30 minutes to 4 hours. and then filtering to remove the extraction residue to obtain an extract. The extract may be further dried by distilling off the extraction solvent.
In addition, it may be used as an extraction raw material after being subjected to pretreatment such as degreasing with a non-polar solvent such as hexane. By performing pretreatment such as degreasing, the extraction treatment with a polar solvent can be efficiently performed.

The conditions (extraction time and extraction temperature), the extraction solvent, and the amount of the extraction solvent used in the extraction of the black ginger are not particularly limited, and can be appropriately selected according to the purpose.

The extraction solvent is not particularly limited and can be appropriately selected depending on the intended purpose. Examples thereof include water, hydrophilic solvents, and mixed solvents of water and hydrophilic solvents.

The water is not particularly limited and can be appropriately selected according to the purpose. Including processed ones. Treatments applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. The water that can be used as the extraction solvent includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered physiological saline, and the like. The water may be used singly or in combination of two or more.

The hydrophilic solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol and glycerin; These may be used individually by 1 type, and may use 2 or more types together.

The amount of the hydrophilic solvent used relative to the water in the mixed solvent is not particularly limited and can be appropriately selected according to the purpose. Part by volume to 90 parts by volume, when using a lower aliphatic ketone, 1 part by volume to 40 parts by volume per 10 parts by volume of water, when using a polyhydric alcohol, 1 part by volume per 10 parts by volume of water It is preferable to add from 1 part to 90 parts by volume.

The temperature of the extraction solvent is not particularly limited and can be appropriately selected depending on the intended purpose.

The obtained black ginger extract is treated by dilution, concentration, drying, purification, etc. according to a conventional method in order to obtain a diluted product, concentrate, dried product, crudely purified product, purified product, etc. of the black ginger extract. may be applied.

The method for purifying the black ginger extract is not particularly limited and can be appropriately selected depending on the intended purpose. Examples thereof include purification methods such as activated carbon treatment, adsorption resin treatment and ion exchange resin treatment. Purification by the above purification method can increase the concentration of active ingredients and remove unnecessary substances.

The obtained black ginger extract can be used as the bone strengthening agent as it is, but the concentrated liquid and the dried product are preferable in terms of ease of use. In obtaining the dried product, a carrier such as dextrin or cyclodextrin may be added to improve hygroscopicity.

<Western ginseng extract>
The ginseng (scientific name: Daucus carota subsp. sativus) is a plant belonging to the genus Ginseng of the family Umbelliferae. It is native to Central Asia, distributed throughout Japan, and easily available from these regions.

The ginseng extract may be prepared from the extraction part used as the raw material for extraction, or may be a commercially available product.

-extracted part-
The part to be extracted from the ginseng is not particularly limited and can be appropriately selected according to the intended purpose. and the like. These may be used individually by 1 type, and may use 2 or more types together. Among these, above-ground parts such as stems, leaves, branches, branches and leaves are preferred.
The shape, structure, and size of the ginseng extraction raw material are not particularly limited, and can be appropriately selected according to the purpose.

-Preparation method of extraction site-
The method for preparing the extracted part of the ginseng is not particularly limited, and can be appropriately selected according to the purpose. can be done by

-extract-
The aspect of the ginseng extract, the extraction, the treatment of the extract, and the purification method of the extract are not particularly limited and can be appropriately selected according to the purpose. It can be performed in the same manner as described in the item of.

<Chou-mei-so extract>
The long-life grass (scientific name: Peucedanum japonicum Thunb.) is a plant belonging to the genus Apiaceae of the family Apiaceae, and is a perennial herb that grows along the coast. It is widely distributed and readily available from these areas.

The Chomeigusa extract may be prepared from the extraction site used as the raw material for extraction, or may be a commercially available product.

-extracted part-
The part from which the Chou-mei-so is extracted is not particularly limited and can be appropriately selected depending on the intended purpose. Underground parts such as rhizomes and the like can be mentioned. These may be used individually by 1 type, and may use 2 or more types together. Among these, underground parts such as roots and rhizomes are preferable.
The shape, structure, and size of the raw material for extraction of Chou-mei-so are not particularly limited, and can be appropriately selected according to the purpose.

-Preparation method of extraction site-
The method for preparing the extracted portion of Chomeisou is not particularly limited, and can be appropriately selected according to the purpose. can be done by

-extract-
The form, extraction, treatment of the extract, and purification method of the extract are not particularly limited and can be appropriately selected according to the purpose. It can be performed in the same manner as described in the item of.

<Gymnema extract>
Gymnema is a climbing plant belonging to the Apocynaceae family, and examples thereof include Gymnema sylvestre. Gymnema originates from India and Sri Lanka and is readily available from these regions.

The gymnema extract may be prepared from the extraction site used as the raw material for extraction, or may be a commercially available product.

-extracted part-
The part from which the gymnema is extracted is not particularly limited and can be appropriately selected depending on the intended purpose. Examples thereof include stems and leaves. These may be used individually by 1 type, and may use 2 or more types together.
The shape, structure, and size of the raw material for extraction of Gymnema are not particularly limited, and can be appropriately selected according to the purpose.

-Preparation method of extraction site-
The method for preparing the extracted part of Gymnema is not particularly limited and can be appropriately selected according to the purpose. can be done.

-extract-
The aspect of the gymnema extract, the extraction, the treatment of the extract, and the purification method of the extract are not particularly limited, and can be appropriately selected according to the purpose. It can be performed in the same manner as described in the item.

<Lotus germ extract>
The lotus (scientific name: Nelumbo nucifera Gaertn.) is a perennial aquatic plant belonging to the family Nymphaeaceae, Nelumbo nucifera Gaertn., native to tropical Asia. Lotus is distributed in southeastern Europe, northern Australia, eastern Asia, etc., and is cultivated in ponds, paddy fields, moats, etc., and can be easily obtained from these regions.
In Japan, the rhizome of the lotus is eaten as lotus root, making it a highly safe plant.

The lotus germ extract may be prepared from the germ used as the raw material for extraction, or may be a commercially available product.

-extracted part-
The extracted part of the lotus is the germ. The lotus germ is the green, rod-shaped germ inside the lotus seed.
The shape, structure, and size of the lotus extraction raw material are not particularly limited, and can be appropriately selected according to the purpose.

-Preparation method of extraction site-
The method for preparing the lotus extract raw material is not particularly limited, and can be appropriately selected according to the purpose. can be done.

-extract-
The aspect of the lotus germ extract, the extraction, the treatment of the extract, and the purification method of the extract are not particularly limited and can be appropriately selected according to the purpose. It can be performed in the same manner as described in the item of.

<Star fruit leaf extract>
The star fruit (scientific name: Averrhoa carambola) (Japanese name: carambola) is an evergreen tree belonging to the family Oxalaceae, genus carambola. The place of origin is all over Southeast Asia, as well as tropical and subtropical regions such as southern China, Taiwan, Brazil, Guyana, Trinidad and Tobago, Florida, and Hawaii, and it is easily available from these regions.
There are two types of star fruit: sweet seeds with sweet fruits and sour seeds with sour fruits. Star fruits are used not only for raw food but also for jams, jellies and pickles. The leaves are used as a prophylactic or therapeutic agent for wind fever, acute gastroenteritis, urination disorder, postpartum edema, and the like.

The star fruit leaf extract may be prepared from leaves used as raw materials for extraction, or may be commercially available products.

-extracted part-
The extraction part of the star fruit is the leaf part.
The shape, structure, and size of the raw material for extraction of star fruit are not particularly limited, and can be appropriately selected according to the purpose.

-Preparation method of extraction site-
The method for preparing the extracted part of the star fruit is not particularly limited, and can be appropriately selected according to the purpose. can be done by

-extract-
The aspect of the star fruit leaf extract, the extraction, the treatment of the extract, and the purification method of the extract are not particularly limited and can be appropriately selected according to the purpose. It can be performed in the same manner as described in the item of extraction.

<Extract of shell ginger leaf>
The shell ginger (scientific name: Alpinia zerumbet or Alpinia speciosa (Wendl.) K. Schum.) is a perennial evergreen herb belonging to the genus Zingiberaceae, and is distributed from southern Kyushu to India. available at
Getto is called sannin in Okinawa, and has been used in moochie, a traditional sweet since the Ryukyu dynasty, and is also used as an herb.

The shell ginger leaf extract may be prepared from the extraction part used as the raw material for extraction, or may be a commercially available product.

-extracted part-
The extraction part of the shell ginger is the leaf part.
The shape, structure, and size of the shell ginger extract raw material are not particularly limited, and can be appropriately selected according to the purpose.

-Preparation method of extraction site-
The method for preparing the extract part of shell ginger is not particularly limited, and can be appropriately selected according to the purpose. can be done by

-extract-
The form, extraction, treatment of the extract, and purification method of the extract are not particularly limited and can be appropriately selected according to the purpose. It can be performed in the same manner as described in the item of.

前記構造式（１）中、Ｒ_１～Ｒ_６はそれぞれ水素（－Ｈ）、ヒドロキシル基（－ＯＨ）、及びメトキシ基（－ＯＣＨ_３）のいずれかであり、かつＲ_１～Ｒ_６は２つ以上のメトキシ基を含む。 <Polymethoxyflavones>
The polymethoxyflavones are compounds represented by the following structural formula (1). The said polymethoxyflavone may be used individually by 1 type, and may use 2 or more types together. The polymethoxyflavones may be in the form of salts. When two or more kinds of polymethoxyflavones are used in combination, the amount of each polymethoxyflavones is not particularly limited and can be appropriately selected according to the purpose.

In the structural formula (1), R ₁ to R ₆ are each hydrogen (-H), hydroxyl group (-OH) or methoxy group (-OCH ₃ ), and R ₁ to R ₆ are 2 contains one or more methoxy groups.

The polymethoxyflavones may be those extracted from plants or chemically synthesized, or commercially available products.

The method for extracting from plants is not particularly limited and can be appropriately selected according to the purpose. Examples thereof include the method of extracting from black ginger described above. Polymethoxyflavones that can be extracted from the black ginger include 5,7,3′,4′-tetramethoxyflavone, 3,5,7,3′,4′-pentamethoxyflavone, 5,7- Dimethoxyflavone, 5,7,4'-trimethoxyflavone, 3,5,7-trimethoxyflavone, and 3,5,7,4'-tetramethoxyflavone. The methoxyflavones preferably include 5,7-dimethoxyflavone and 3,5,7,3',4'-pentamethoxyflavone.

The method for extracting the polymethoxyflavones from the black ginger is not particularly limited, and a known method can be appropriately selected. Examples thereof include the method described in JP-A-2016-193906.

<Corosolic acid>
The corosolic acid is a pentacyclic triterpenic acid contained in plants and represented by the following structural formula (2). The corosolic acid may be in the form of a salt.

The corosolic acid may be extracted from plants, chemically synthesized, or commercially available.

The method of extracting from plants is not particularly limited and can be appropriately selected according to the purpose. Examples thereof include a method of extracting from banaba.

The banaba (scientific name: Lagerstroemia speciose) is a loosestrife plant, distributed in tropical regions from India and Southeast Asia to northern Australia, and easily available from these regions.
The method for extracting the corosolic acid from the banaba is not particularly limited, and a known method can be appropriately selected.

前記構造式（３）中、Ｒ_７は－Ｏ－ＣＯＣＨ_３であり、Ｒ_８は－Ｏ－Ａｇである。なお、前記「Ａｇ」は下記構造式（３ａ）で表されるアンゲロイル基を表す。

<Pterixin>
The pterixin is a compound represented by the following structural formula (3). The pterixin may be in the form of a salt.

In structural formula (3) above, R ₇ is —O—COCH ₃ and R ₈ is —O—Ag. In addition, the above "Ag" represents an angeloyl group represented by the following structural formula (3a).

The pterixin may be extracted from plants, chemically synthesized, or commercially available.

The method of extracting from plants is not particularly limited and can be appropriately selected according to the purpose.

The method for extracting the pterixin from the Chou-mei-so is not particularly limited, and a known method can be appropriately selected.

<Dihydro-5,6-dehydrokawaine>
The dihydro-5,6-dehydrokawaine is a compound represented by the following structural formula (4). The dihydro-5,6-dehydrokawaine may be in the form of a salt.

The dihydro-5,6-dehydrokawaine may be extracted from plants, chemically synthesized, or commercially available.

The method for extracting from plants is not particularly limited and can be appropriately selected according to the purpose.

The method for extracting the dihydro-5,6-dehydrokawaine from the shell ginger is not particularly limited, and can be appropriately selected from known methods, such as the method described in International Publication No. 2016/103450. are mentioned.

The above polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrocawain, black ginger extract, western carrot extract, Chomei grass extract, gymnema extract, lotus germ extract, star fruit leaf extract, and alpinia leaf extract, and any of the bone strengthening agents selected from the group consisting of combinations of two or more thereof, are not particularly limited, and the polymethoxyflavones, corosolic acid, pterixin , dihydro-5,6-dehydrokawaine, black ginger extract, ginseng extract, claustrophyte extract, gymnema extract, lotus germ extract, star fruit leaf extract, and shell ginger leaf extract, and two of these Any physiological activity selected from the group consisting of combinations of species or more can be appropriately adjusted. The bone strengthening agent includes the polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrokawaine, black ginger extract, ginseng extract, long-life herb extract, gymnema extract, lotus germ extract, It may consist of only one selected from the group consisting of a star fruit leaf extract, shell ginger leaf extract, and a combination of two or more thereof.

<Other ingredients>
The other components are not particularly limited and can be appropriately selected according to the form of use of the bone strengthening agent. Antioxidants, sweeteners, acidulants, seasonings, coloring agents, fragrances, whitening agents, moisturizers, oily ingredients, UV absorbers, surfactants, thickeners, alcohols, powder ingredients, coloring agents, aqueous ingredients , water, and skin nutrients. These may be used individually by 1 type, and may use 2 or more types together.

The content of the other components in the bone strengthening agent is not particularly limited and can be appropriately selected depending on the purpose.

<Application>
Applications of the bone strengthening agent are not particularly limited and can be appropriately selected according to the intended purpose.
Since the bone strengthening agent has an excellent bone strengthening effect and is highly safe, it can be suitably used, for example, as an active ingredient of a bone strengthening composition.

The bone strengthening agent of the present invention is preferably applied to humans, but as long as its action and effect are exhibited, it can be used in animals other than humans (for example, mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.).

The method of use of the bone strengthening agent is not particularly limited and can be appropriately selected according to the purpose, and examples thereof include oral, parenteral and external use.

The dosage form of the bone strengthening agent is not particularly limited and can be appropriately selected depending on the intended purpose. parenteral administration such as drug, drip, suppository; lotion, milky lotion, cream, ointment, serum, lotion, mask, jelly, lip balm, lipstick, foundation, bath agent, soap, body soap, astringent, hair External preparations such as tonics, hair lotions, hair creams, hair liquids, pomades, shampoos, rinses and conditioners.
The method for producing each dosage form of the bone strengthening agent is not particularly limited, and a known method can be appropriately selected.

There are no particular restrictions on the amount of use, period of use, and other methods of use of the bone strengthening agent, and they can be appropriately selected according to the intended purpose.

The bone strengthening agent of the present invention can also be used as a reagent for research on the action mechanism of bone strengthening action.

The above polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrocawain, black ginger extract, western carrot extract, Chomei grass extract, gymnema extract, lotus germ extract, star fruit leaf extract, and shell ginger leaf extract, and the bone strengthening action of any selected from the group consisting of a combination of two or more thereof, for example, the action of promoting type I collagen production in osteoblasts and the action of activating osteoblasts demonstrated by at least one. Therefore, the bone strengthening agent preferably has at least one of type I collagen production promoting action in osteoblasts and osteoblast activating action. The above polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrocawain, black ginger extract, western ginseng extract, long-life herb extract, gymnema extract, lotus germ extract, star fruit leaf extract The bone-strengthening action of any one selected from the group consisting of a substance, and shell ginger leaf extract, and a combination of two or more thereof is an action of promoting type I collagen production in osteoblasts and an action of activating osteoblasts. It is not limited to the bone-strengthening action exerted based on at least one of them.
The present invention also provides the polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrokawaine, black ginger extract, ginseng extract, long-life herb extract, gymnema extract, lotus germ extract, An agent for promoting type I collagen production in osteoblasts or an activating agent for osteoblasts, containing any selected from the group consisting of star fruit leaf extract, shell ginger leaf extract, and combinations of two or more thereof also related to

(Bone strengthening composition)
The bone strengthening composition of the present invention contains the bone strengthening agent of the present invention and, if necessary, other ingredients.

<Bone strengthening agent>
The bone strengthening agent is the bone strengthening agent of the present invention described above.

The content of the bone strengthening agent in the bone strengthening composition is not particularly limited. , black ginger extract, ginseng extract, chomeiso extract, gymnema extract, lotus germ extract, star fruit leaf extract, shell ginger leaf extract, and combinations of two or more thereof The above polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrokawaine, black ginger extract, ginseng extract, chomeiso extract 0.00 in terms of the total amount selected from the group consisting of a substance, gymnema extract, lotus germ extract, star fruit leaf extract, shell ginger leaf extract, and combinations of two or more thereof. 0001% by mass to 20% by mass is preferable, and 0.0001% by mass to 10% by mass is more preferable. The bone strengthening composition may consist of only the bone strengthening agent.

<Other ingredients>
Other ingredients in the bone strengthening composition are not particularly limited, and can be appropriately selected according to the form of use of the bone strengthening composition. and the like. These may be used individually by 1 type, and may use 2 or more types together.

The content of the other components in the bone strengthening composition is not particularly limited and can be appropriately selected depending on the purpose.

<Aspect>
The aspect of the bone strengthening composition is not particularly limited and can be appropriately selected according to the purpose. Examples thereof include pharmaceuticals, quasi-drugs, food and drink, and cosmetics.
The bone strengthening composition of the present invention can be used on a daily basis, and contains active ingredients such as polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrokawaine, black ginger extract, and Western extract. Carrot extract, Chomeisou extract, Gymnema extract, lotus germ extract, star fruit leaf extract, shell ginger leaf extract, and combination of two or more thereof , various physiologically active actions including bone strengthening action can be exerted extremely effectively.

The bone-strengthening composition of the present invention is preferably applied to humans, but can be applied to animals other than humans (for example, mice, rats, hamsters, dogs, and cats) as long as the effects of each are exhibited. , cows, pigs, monkeys, etc.).

The usage of the bone strengthening composition of the present invention is not particularly limited, and can be appropriately selected according to the purpose. Examples thereof include oral, parenteral, and external usage.

Examples of the oral compositions include the above-described oral administration agents and food and drink. Here, “food and drink” refers to those that are less likely to harm human health and are taken orally or through the gastrointestinal tract in normal social life. It is not limited to categories such as Therefore, the food and drink include orally ingested general food, health food (functional food and drink), food with health claims (food for specified health use, food with nutrient function claims, food with function claims), quasi-drugs, pharmaceuticals means a wide range of foods and drinks that constitute

The type of the oral composition is not particularly limited and can be appropriately selected depending on the intended purpose. Beverages such as coffee drinks and coffee-containing soft drinks (including concentrated undiluted solutions and powders for preparation of these drinks); Frozen desserts such as ice cream, ice sherbet, and shaved ice; Noodles such as Chinese noodles and instant noodles; Candies, candies, gums, chocolates, tablets, snacks, biscuits, jellies, jams, creams, baked goods, breads and other confectionery; Crabs, salmon, short-necked clams, tuna, sardines, and shrimps , bonito, mackerel, whale, oyster, Pacific saury, squid, red clam, scallop, abalone, sea urchin, salmon roe, tokobushi, etc.; marine and livestock processed foods such as kamaboko, ham, sausage; dairy products such as processed milk and fermented milk Oils and fats such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressings, and oil-and-fat processed foods; Seasonings such as sauces and sauces; Retort pouch foods such as tendon, eel bowl, hayashi rice, oden, mapo doufu, gyudon, meat sauce, egg soup, omelet rice, dumplings, shumai, hamburgers, meatballs; side dishes such as salads and pickles; various forms of health, beauty, and nutrition Supplementary foods; medicines such as tablets, granules, capsules, drinks, lozenges, and mouthwashes; quasi-drugs; be done.

Examples of the non-oral compositions include the above-described parenteral agents and external agents. For example, ointments, creams, milky lotions, lotions, packs, and foundations can be used as skin cosmetics, and hair tonics, hair creams, hair liquids, shampoos, pomades, rinses, and the like can be used as hair cosmetics.

The method for producing the bone strengthening composition is not particularly limited, and can be appropriately selected depending on the form of use of the bone strengthening composition.

The usage amount, usage period, and the like of the bone strengthening composition are not particularly limited, and can be appropriately selected according to the purpose.

As described above, the bone strengthening agent and bone strengthening composition of the present invention have excellent bone strengthening action.
Accordingly, the present invention also relates to a bone strengthening method comprising administering at least one of the bone strengthening agent and the bone strengthening composition to an individual.

Production examples, test examples, and compounding examples of the present invention will be described below, but the present invention is not limited to these production examples, test examples, and compounding examples.

Test samples used in Test Examples 1 and 2 described below were produced or prepared as follows.

(Production Example 1: Polymethoxyflavones)
Polymethoxyflavones were produced as follows.
1,000 mL of 60% by volume ethanol was added to 100 g of the rhizome of black ginger, extracted at 80° C. for 2 hours using a reflux condenser, and then filtered through filter paper to obtain an extract.
The resulting extract is concentrated to prepare a solid content concentration of 5% and an ethanol concentration of 40% by volume, and the prepared solution is passed through the resin volume to a solid content of about 5% to adsorb polymethoxyflavones to the resin. , 40% by volume ethanol, and then eluted with 75% by volume ethanol to obtain an eluate. The obtained eluate was concentrated and dried under reduced pressure to obtain 5.7 g of polymethoxyflavone (21.7% by mass of 5,7-dimethoxyflavone, 3,5,7,3′,4′-pentamethoxyflavone containing 22.3% by mass) was obtained.

(Production Example 2: Black ginger extract)
A 60% by volume ethanol extract of the rhizome of black ginger was prepared as follows.
1,000 mL of 60% by volume ethanol was added to 100 g of the rhizome of black ginger, extracted at 80° C. for 2 hours using a reflux condenser, and then filtered through filter paper to obtain an extract.
The resulting extract was concentrated and dried under reduced pressure to obtain 23.9 g of a 60 vol % ethanol extract (powder) of the rhizome of black ginger.

(Production Example 3: Western carrot extract (30% ethanol extract))
A 30% by volume ethanol extract of the aerial parts of ginseng was prepared as follows.
360 mL of 30% by volume ethanol was added to 30 g of the above-ground part of the carrot, and extraction was performed twice at 80° C. for 1 hour using a reflux condenser, followed by filtration with filter paper to obtain an extract.
The resulting extract was concentrated and dried under reduced pressure to obtain 2.28 g of a 30 vol % ethanol extract (powder) of the aerial part of ginseng.

(Production Example 4: Western carrot extract (80% ethanol extract))
1.69 g of an 80% by volume ethanol extract (powder) of the aerial parts of ginseng was obtained in the same manner as in Production Example 3, except that the 30% by volume ethanol was replaced with 80% by volume ethanol.

(Production Example 5: Chomeisou extract (30% ethanol extract))
A 30 vol % ethanol extract of the root of Chomeigusa was prepared as follows.
200 mL of 30% by volume ethanol was added to 10 g of roots of Chomeigusa, extracted at 80° C. for 1 hour using a reflux condenser, and then filtered through filter paper to obtain an extract.
The resulting extract was concentrated and dried under reduced pressure to obtain 2.28 g of a 30 vol % ethanol extract (powder) of the root of Chou-mei-so.

(Production Example 6: Chomeisou extract (80% ethanol extract))
1.90 g of an 80% by volume ethanol extract (powder) of roots of Chou-mei-so was obtained in the same manner as in Production Example 5, except that 30% by volume ethanol was replaced with 80% by volume ethanol.

(Production Example 7: lotus germ extract)
A 50% by volume ethanol extract of lotus germ was prepared as follows.
270 mL of 50% by volume ethanol was added to 30 g of lotus germ, and extracted twice at 80° C. for 1 hour using a reflux condenser, followed by filtration through filter paper to obtain an extract.
The resulting extract was concentrated and dried under reduced pressure to obtain 8.4 g of a 50 volume % ethanol extract (powder) of lotus germ.

(Production Example 8: Star fruit leaf extract)
A 30% by volume ethanol extract of star fruit leaves was prepared as follows.
1,600 mL of 30% by volume ethanol was added to 100 g of the leaves of star fruit, extracted twice at 80° C. for 1 hour using a reflux condenser, and then filtered through filter paper to obtain an extract.
The resulting extract was concentrated and dried under reduced pressure to obtain 32.9 g of a 30 vol % ethanol extract (powder) of star fruit leaves.

(Manufacturing Example 9: shell ginger leaf extract)
A 50 vol % ethanol extract of the leaves of Alpinia speciosa was prepared as follows.
1,000 mL of 50% by volume ethanol was added to 100 g of the leaves of shell ginger, and extraction was performed twice at 80° C. for 1 hour using a reflux condenser, followed by filtration with filter paper to obtain an extract.
The resulting extract was concentrated and dried under reduced pressure to obtain 13.3 g of a 50 vol % ethanol extract (powder) of the leaves of shell ginger.

(Production Examples 10-13)
Commercially available products were prepared for the following test samples.
・ Production Example 10: Gymnema extract powder FG (manufactured by Maruzen Pharmaceutical Co., Ltd.)
・ Production Example 11: Corosolic acid (Fujifilm Wako Pure Chemical Industries, Ltd.)
・ Production Example 12: Pterixin (Chem Faces)
・ Production Example 13: Dihydro-5,6-dehydrokawaine (Toronto Research Chemicals)

(Test Example 1: Type I collagen production promotion effect test using osteoblasts)
Using the products produced or prepared in the above production examples as test samples, the type I collagen production promoting action in osteoblasts was tested by the following test method.

Human osteoblasts (SaM-1) were cultured in 10% FBS-containing DMEM (high glucose with 20 mmol/L HEPES: High-DMEM), and the cells were collected by trypsinization. After diluting the collected cells with the above medium to a concentration of 6×10 ⁴ cells/mL, seed 200 μL per well in a 96-well microplate at 1.2×10 ⁴ cells/well, Cultured for 3 days.
After completion of the culture, the cells were washed with 100 μL/well PBS(−), and the medium was replaced with 100 μL/well of High-DMEM without FBS. After culturing for 24 hours, test samples dissolved in FBS-free High-DMEM (see Tables 1-1 to 1-2 below for sample concentrations) or FBS-free High-DMEM to which no test sample was added (control) were added to each well. 100 μL was added to and cultured for 3 days. After completion of the culture, the amount of type I collagen in the medium of each well was measured by ELISA.
From the obtained results, the rate of promotion of type I collagen production was calculated according to the following formula. The results are shown in Tables 1-1 and 1-2.
Type I collagen production promotion rate (%) = A/B x 100
A to B in the above formula each represent the following.
A: Type I collagen amount when test sample is added B: Type I collagen amount when test sample is not added (control)

From the results in Tables 1-1 and 1-2, polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrokawaine, black ginger extract, ginseng extract, long-life herb extract, gymnema extract, It was confirmed that the lotus germ extract, the star fruit leaf extract, and the shell ginger leaf extract have an excellent type I collagen production-promoting action in osteoblasts.

(Test Example 2: Osteoblast activation test)
The osteoblast activating action was tested by the test method described below, using the product produced or prepared in the above production example as a test sample.

Human osteoblasts (SaM-1) were cultured in 10% FBS-containing DMEM (high glucose with 20 mmol/L HEPES: High-DMEM), and the cells were collected by trypsinization. After diluting the collected cells with the above medium to a concentration of 6×10 ⁴ cells/mL, seed 200 μL per well in a 96-well microplate at 1.2×10 ⁴ cells/well, Cultured for 3 days.
After completion of the culture, the cells were washed with 100 μL/well PBS(−), and the medium was replaced with 100 μL/well of High-DMEM without FBS. After culturing for 24 hours, 100 μL of a test sample dissolved in FBS-free High-DMEM (see Table 2 below for sample concentrations) or FBS-free High-DMEM (control) containing no test sample was added to each well. cultured for days.
The osteoblast activation action was measured using the WST8 assay using cellular reductase activity as an indicator. Specifically, after culturing, 10 μL of WST-8 solution (Cell Counting Kit-8, Dojindo Laboratories) was added to each well. After culturing for 2 hours, the absorbance at a wavelength of 450 nm was measured as extracellularly generated formazan. At the same time, absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was taken as the amount of formazan produced.
From the obtained results, the osteoblast activation rate was calculated according to the following formula. Table 2 shows the results.
Osteoblast activation rate (%) = A/B x 100
A to B in the above formula each represent the following.
A: Amount of formazan produced when the test sample is added B: Amount of formazan produced when the test sample is not added (control)

From the results in Table 2, it was confirmed that pterixin and the Choumeisou extract have an excellent osteoblast activation effect.

(Composition example 1)
A tablet having the following composition was produced by a conventional method.
・ 5.0 mg of black ginger extract of Production Example 2
・ Dolomite 83.4 mg
(Contains 20% calcium and 10% magnesium)
・ Casein phosphopeptide 16.7 mg
・Vitamin C 33.4mg
・ Maltitol 136.8 mg
・ Collagen 12.7mg
・ Sucrose fatty acid ester 12.0 mg

(Formulation example 2)
An oral liquid preparation having the following composition was prepared by a conventional method.
<Composition in 1 ampoule (100 mL per bottle)>
・ 0.3% by mass of dihydro-5,6-dehydrokawaine of Production Example 13
・ Sorbit 12.0% by mass
・ Sodium benzoate 0.1% by mass
・ Perfume 1.0% by mass
・ Calcium sulfate 0.5% by mass
・ Remainder of purified water

(Composition example 3)
A emulsion having the following composition was prepared by a conventional method.
・ 0.01 g of the ginseng extract of Production Example 3
・ Jojoba oil 4.00g
・ 1,3-butylene glycol 3.00g
・ Arbutin 3.00g
- Polyoxyethylene cetyl ether (20 E.O.) 2.50 g
・ Olive oil 2.00g
・ Squalane 2.00g
・ Cetanol 2.00g
・ 2.00 g of glyceryl monostearate
・ 2.00 g of polyoxyethylene sorbitan oleate (20E.O.)
・ 0.15 g of methyl paraoxybenzoate
・ Stearyl glycyrrhizinate 0.10g
・ Huangji extract 0.10g
・ Dipotassium glycyrrhizinate 0.10 g
・ Ginkgo biloba extract 0.10g
・ Conchiolin 0.10g
・ Phellodendron bark extract 0.10g
・ Chamomile extract 0.10g
・ Perfume 0.05g
・ Remainder of purified water (the total amount shall be 100 g)

(Composition example 4)
A beauty essence having the following composition was produced by a conventional method.
・ 0.01 g of Chomeisou extract of Production Example 6
・ Chamomile extract 0.1g
・Xanthan gum 0.3g
・ 0.1 g of hydroxyethyl cellulose
・ Carboxyvinyl polymer 0.1 g
・ 4.0 g of 1,3-butylene glycol
・ Dipotassium glycyrrhizinate 0.1g
・ 2.0 g of glycerin
・ Potassium hydroxide 0.25 g
・ Perfume 0.01g
・ Preservative (methyl parahydroxybenzoate) 0.15g
・ Ethanol 2.0g
・ Remainder of purified water (the total amount shall be 100 g)

(Composition example 5)
Granules having the following composition were produced by a conventional method.
・ Gymnema extract of Production Example 10 150.0 parts by mass ・ Calcium 680.0 parts by mass ・ Iron 6.8 parts by mass ・ Beet oligosaccharide 1000.0 parts by mass ・ Stevia extract 10.0 parts by mass

(Formulation example 6)
A soft capsule having the following composition was produced by a conventional method.
・30 parts by mass of lotus germ extract of Production Example 7 ・200 parts by mass of olive oil ・24 parts by mass of glycerin fatty acid ester ・24 parts by mass of beeswax

(Formulation Example 7)
A chocolate having the following composition was produced by a conventional method.
- Star fruit leaf extract of Production Example 8 0.15 parts by mass - Chocolate 45.0 parts by mass - Sucrose 15.0 parts by mass - Cocoa butter 20.0 parts by mass - Whole milk powder 25.0 parts by mass

(Formulation Example 8)
A soft drink having the following composition was produced by a conventional method.
・ 0.3% by mass of corosolic acid in Production Example 11
・ Royal jelly 1.0% by mass
・ Water-soluble collagen 10.0% by mass
・ Adlay extract 1.0% by mass
・ Korean ginseng extract 1.0% by mass
・ Oligosaccharide 5.0% by mass
・ Sucrose 10.0% by mass
・ Prune juice 2.0% by mass
・ Pomegranate juice 5.0% by mass
・ Grapefruit juice 10.0% by mass
・ Grapefruit flavor 0.7% by mass
・ Remainder of water ・ Total 100.0% by mass

Claims (3)

Polymethoxyflavones, corosolic acid, pterixin, dihydro-5,6-dehydrocawain, black ginger extract, western carrot extract, long life herb extract, gymnema extract, lotus germ extract, star fruit leaf extract, and A bone strengthening agent characterized by containing any one selected from the group consisting of shell ginger leaf extract and a combination of two or more thereof. 2. The bone strengthening agent according to claim 1, which has at least one of type I collagen production promoting action in osteoblasts and osteoblast activating action. A bone strengthening composition comprising the bone strengthening agent according to claim 1 .