JP6742575B2 - Joint function improving composition - Google Patents

Description

The present invention relates to a composition capable of improving joint function, and more particularly, to a composition containing glucosamine and certain other components as active ingredients.

As the population ages, the population suffering from joint pain such as knee and elbow pain is increasing, and pharmaceuticals and the like that relieve such joint pain are desired. As a material having an effect of improving arthritis, which is one of the causes of joint pain, attention has been paid to amino sugars such as glucosamine (see Patent Document 1).

JP, 2003-325136, A

An object of the present invention is to provide a composition capable of protecting cartilage and improving joint function.

In order to improve joint function, the present inventors have diligently investigated and studied cartilage existing in a joint part, and found that a high cartilage protective effect can be obtained by combining glucosamine and a specific other component. The present invention has been completed. That is, it has been found that the cartilage can be protected more effectively by combining glucosamine and a specific other component having little or little cartilage protective ability.

That is, the present invention relates to a composition containing glucosamine and at least one component selected from the group consisting of the following (a) to (f) as active ingredients.
(A) at least one plant material selected from barley, long-lived grass, kudzu, rice, maqui berry, and ginger (b) at least one functional additive selected from aspartame, sucrose fatty acid ester, and calcium stearate ( c) at least one amino acid selected from alanine, asparagine, glutamic acid, histidine, isoleucine, leucine, phenylalanine, proline, serine, tyrosine, valine, and S-adenosylmethionine (d) gallic acid, and chlorogenic acid At least one polyphenol (e) at least one selected from vitamin A, vitamin B1, vitamin B2, vitamin B12, vitamin C, vitamin D3, sodium pantothenate, niacin, biotin, vitamin K, β-carotene, calcium and selenium Vitamins and minerals (f) at least one cartilage component selected from proteoglycans and type II collagen

The composition of the present invention can be used as a joint function improving agent having a cartilage protecting action.

The composition of the present invention may be obtained by adding an active ingredient comprising glucosamine and at least one ingredient selected from the group consisting of (a) to (f).

The composition of the present invention is preferably for oral use, and is preferably a tablet, capsule, powder, granule, or solution.

The present invention also relates to a method for improving joint function (excluding medical procedures), which comprises ingesting the composition of the present invention.

The composition of the present invention can protect cartilage and improve joint function.

It is a figure which shows the expression level of MMP3 when a composition (glucosamine + plant material) of the present invention is applied to chondrocytes (NHAc-kn), the upper left figure shows the one using barley as the plant material, and the upper right figure. Shows the one using long-lived grass as the plant material, the lower left figure shows the one using kudzu as the plant material, and the lower right figure shows the one using rice (rice bran) as the plant material. It is a figure which shows the expression level of MMP3 at the time of applying the composition (glucosamine + plant material) of this invention to a chondrocyte (NHAc-kn), the upper left figure shows what used Maki berry as a plant material, and the upper right figure. Shows the one using red ginger (Zingiber officinale var. Rubra) as the plant material, and the lower left diagram shows the one using ginger (Zingiber officinale) as the plant material. It is a figure which shows the expression level of MMP3 when the composition (glucosamine + functional additive) of the present invention is applied to chondrocytes (NHAc-kn), and the upper left figure shows the one using aspartame as a functional additive. The upper right figure shows the one using sucrose fatty acid ester as the functional additive, and the lower left figure shows the one using calcium stearate as the functional additive. It is a figure which shows the expression level of MMP3 when the composition (glucosamine + amino acid) of this invention is applied to chondrocyte (NHAc-kn), the upper left figure shows what used alanine as an amino acid, and the upper right figure shows amino acid. Shows the case using asparagine, the lower left figure shows the one using glutamic acid as the amino acid, and the lower right figure shows the one using histidine as the amino acid. It is a figure which shows the expression level of MMP3 when a composition (glucosamine + amino acid) of the present invention is applied to chondrocytes (NHAc-kn), the upper left figure shows the one using isoleucine as the amino acid, and the upper right figure shows the amino acid. Shows the one using leucine, the lower left figure shows the one using phenylalanine as the amino acid, and the lower right figure shows the one using proline as the amino acid. It is a figure which shows the expression level of MMP3 when the composition (glucosamine + amino acid) of this invention is applied to chondrocyte (NHAc-kn), the upper left figure shows what used serine as an amino acid, and the upper right figure shows amino acid. And tyrosine is used as the amino acid, the lower left diagram shows the one using valine as the amino acid, and the lower right diagram shows the one using S-adenosylmethionine (SAMe) as the amino acid. It is a figure which shows the expression level of MMP3 when a composition (glucosamine + polyphenol) of the present invention is applied to chondrocytes (NHAc-kn), the left figure shows the one using gallic acid as a polyphenol, and the right figure The one using chlorogenic acid as the polyphenol is shown. It is a figure which shows the expression level of MMP3 when the composition (glucosamine+vitamins/minerals) of the present invention is applied to chondrocytes (NHAc-kn), and the upper left figure shows the one using vitamin A as vitamins. The upper right figure shows the one using vitamin B1 as the vitamins, the lower left figure shows the one using vitamin B2 as the vitamins, and the lower right figure shows the one using vitamin B12 as the vitamins. It is a figure which shows the expression level of MMP3 when the composition (glucosamine + vitamins and minerals) of the present invention is applied to chondrocytes (NHAc-kn), and the upper left figure shows the one using vitamin C as vitamins. The upper right figure shows the one using vitamin D3 as the vitamins, the lower left figure shows the one using sodium pantothenate as the vitamins, and the lower right figure shows the one using niacin as the vitamins. It is a figure showing the expression level of MMP3 when the composition (glucosamine + vitamins and minerals) of the present invention is applied to chondrocytes (NHAc-kn), and the upper left figure shows the one using biotin as vitamins, The upper right figure shows the one using vitamin K as the vitamins, and the lower left figure shows the one using β-carotene as the vitamins. It is a figure which shows the expression level of MMP3 when the composition (glucosamine + vitamins and minerals) of the present invention is applied to chondrocytes (NHAc-kn), and the upper left figure shows the one using fossil coral Ca as minerals. The upper right figure shows the one using calcined shell Ca as the minerals, the lower left figure shows the one using uncalcined shell Ca as the minerals, and the lower right figure shows the one using milk Ca as the minerals. It is a figure which shows the expression level of MMP3 at the time of applying the composition (glucosamine + vitamins and minerals) of this invention to chondrocyte (NHAc-kn), and shows what used selenium as minerals. It is a figure which shows the expression level of MMP3 when the composition of this invention (glucosamine + cartilage component) is applied to chondrocytes (NHAc-kn), the left figure shows what used proteoglycan as a cartilage component, and the right figure. Shows that type II collagen was used as a cartilage component.

The composition of the present invention is characterized by containing glucosamine and at least one component selected from the group consisting of the following (a) to (f) (hereinafter sometimes referred to as other component) as active ingredients: To do. The following components (a) to (f) used together with glucosamine may be used alone (for example, the component (a)), or may be used in combination of two or more. When two or more other components are used in combination, it is preferable to combine the other components having a high synergistic effect with glucosamine.

The composition (joint function improving composition) of the present invention can protect cartilage by suppressing the destruction of chondrocytes, and more effectively improve joint pain (including prevention). Since it can be sufficiently exerted, it can be used as a joint function improving agent. Further, the joint function-improving composition of the present invention can protect cartilage of the whole body and improve pain of joints of the whole body, but particularly protects cartilage of the hip, hip joint, and knee joints, and pains at such places. Can be improved, which can improve joint function.

[Glucosamine]
As the glucosamine of the present invention, glucosamine, a salt thereof, and N-acetylglucosamine can be used. Examples of the salt include hydrochloride, sulfate, phosphate and the like. Such glucosamine may be of biological origin or may be chemically synthesized.

[Other ingredients]
(A) Plant Material In the joint function-improving composition of the present invention, it is preferable to use, together with glucosamine, at least one plant material selected from barley, long-life grass, kudzu, rice, maqui berry, and ginger as an active ingredient. ..

These plant materials may be any part of the plant such as leaves, stems, roots, flowers, fruits, trunks, branches, etc. In addition to the plant materials themselves (including dried products), crushed products and squeezed juices thereof. It is possible to use a processed plant material such as an extract. Examples of the pulverized product include powder and granules. The squeezed juice and the extract may be in liquid form, but may be used in the form of paste or dry powder. The extract can be obtained by extracting with a suitable solvent, and as the solvent, for example, water (hot water), ethanol, or hydrous ethanol can be used. As these plant materials, commercially available products can be used.

As barley, two-row barley, six-row barley, etc. can be used. The parts used as the plant material of the present invention are preferably stems and leaves, and particularly preferably young leaves.

The long-lived plant is a perennial plant also known as Botanbohu, which belongs to the genus Kawaraboufu of the family Apiaceae. The site used as the plant material of the present invention is preferably a leaf or a root.

Kuzu is a climbing perennial plant of the genus Leguminosae. As the part used as the plant material of the present invention, flowers and roots are preferable, and flowers are particularly preferable. As Katsura flowers, those collected in any process from buds to fully opened flowers may be used, and those collected in each process may be mixed and used. The type of kudzu is not particularly limited, and examples thereof include Pueraria thomsonii, Pueraria lobata, and Pueraria thunbergiana.

Rice is a plant belonging to the genus Poaceae. As the part used as the plant material of the present invention, the outer coat and embryo of brown rice are preferable, and specifically, it is preferable to use rice bran obtained as a by-product when whitening brown rice. The type of rice is not particularly limited, and examples thereof include Japonica variety and Indica variety.

Maki berry is a plant of the family Portaaceae whose origin is Patagonia, Chile, and its scientific name is Aristotellia chilensis. Fruits are preferable as the site used as the plant material of the present invention.

Ginger is a plant belonging to the genus Ginger of the ginger family, and examples thereof include Sanshu ginger and yellow ginger whose scientific name is Zingiber officinale. Also, red ginger (local name is Jahe merah) whose scientific name is Zingiber officinale var. Rubra cultivated in Indonesia or India can be preferably used. A rhizome is preferable as a site used as the plant material of the present invention.

(B) Functional Additive In the joint function improving composition of the present invention, at least one functional additive selected from aspartame, sucrose fatty acid ester, and calcium stearate is used as an active ingredient together with glucosamine. preferable. Aspartame can be used as a sweetener and the like, and sucrose fatty acid ester and calcium stearate can be used as a lubricant and the like.

(C) Amino Acid In the joint function-improving composition of the present invention, alanine, asparagine, glutamic acid, histidine, isoleucine, leucine, phenylalanine, proline, serine, tyrosine, valine, and S-adenosylmethionine are used as active ingredients together with glucosamine. It is preferable to use at least one amino acid (including salt) selected from the following. Examples of the salt include sodium salt, hydrochloride and the like.
(D) Polyphenol In the joint function improving composition of the present invention, it is preferable to use at least one polyphenol selected from gallic acid and chlorogenic acid as an active ingredient together with glucosamine.

(E) Vitamin/Minerals In the joint function-improving composition of the present invention, vitamin A, vitamin B1, vitamin B2, vitamin B12, vitamin C, vitamin D3, sodium pantothenate, niacin, and biotin are included as active ingredients together with glucosamine. It is preferable to use at least one vitamin/mineral selected from vitamin K, β-carotene, calcium and selenium. In addition, calcium and selenium as minerals of the present invention include a form of a compound containing these metals.

(F) Cartilage component In the joint function improving composition of the present invention, it is preferable to use at least one cartilage component selected from proteoglycan and type II collagen as an active ingredient together with glucosamine.

Proteoglycan is a complex polysaccharide in which glycosaminoglycans such as chondroitin sulfate and dermatan sulfate are covalently bound to a protein as a core, and abundant in animal tissues, particularly cartilage tissues. It is also known that proteoglycan exists in the body in a structure in which a core protein is further bound to hyaluronic acid, and its molecular weight is as large as tens of thousands to tens of millions. Specific examples of the proteoglycan used in the present invention include animal-derived proteoglycans, and commercially available products can be used.

Type II collagen is a collagen that is abundantly contained in cartilage, and for example, the one extracted from cartilage of chicken, pig, etc. can be used, and a commercially available product can be used.

The joint function-improving composition of the present invention can be used as a joint function-improving agent having a protective effect on cartilage, and the joint function-improving agent contains glucosamine and other predetermined components and is used for improving joint function. In the above, the product is not particularly limited as long as it can be distinguished from other products. For example, a display indicating that any one of the main body, the packaging, the instruction manual, and the advertisement of the product according to the present invention has a function of improving the joint function is included in the scope of the present invention. For example, so-called health foods such as pharmaceuticals (including quasi-drugs), cosmetics, foods for specified health uses, foods with nutritional function, foods with functional claims, etc. Can be mentioned. In so-called health foods, "for knee and lower back problems", "for a healthy walk", "for a light movement", "to adjust joint function", "to smooth joint movement", "joint function" It is possible to exemplify the display of "improve", "alleviate worries about joint movement", "help joint movement", "support joint movement", and the like. The joint function-improving composition of the present invention can be taken by anyone who is concerned about the above effects regardless of sex or age, but the effect of the joint function-improving composition of the present invention is more effectively enjoyed. Therefore, it is desirable that healthy people other than sick persons should take it, and in particular, elderly persons who have the above-mentioned troubles should take it.

The joint function improving composition of the present invention can be used orally or externally. The external preparation is not particularly limited as long as it is applied to the skin, scalp, etc., and its form includes ointments, creams, gels, lotions, emulsions, packs, poultices, etc. Examples thereof include external preparations for skin and injections.

When the joint function-improving composition of the present invention is used as an oral preparation, its form is, for example, a tablet, capsule, powder, granule, liquid, granule, rod-shaped agent, plate-shaped agent, block-shaped agent. , Solid agents, round agents, paste agents, cream agents, caplet agents, gel agents, chewable agents, stick agents and the like. Of these, tablets, capsules, powders, granules, and liquids are particularly preferable. Specifically, supplements, bottled beverages filled in PET bottles, cans, bottles, etc., instant powdered beverages and instant granule beverages to be dissolved in water (hot water), milk, fruit juice, green juice, etc. Can be illustrated. These are preferable in that they can be easily taken at meals and the taste can be enhanced.

The content of glucosamine and other components (active ingredients) in the composition for improving joint function of the present invention may be appropriately contained within the range where the effect is exhibited.

Generally, when the composition for improving joint function of the present invention is a medicine or a supplement (tablet, capsule), the active ingredient is contained in an amount of 0.01 to 100% by mass based on the dry mass. Preferably, the content is 0.1 to 85% by mass, more preferably 0.5 to 70% by mass.

When the joint function improving composition of the present invention is a packaged beverage (solution), it is preferable that the active ingredient is contained in an amount of 0.01 to 15% by mass based on the dry mass, and 0.03 to 12 The content is more preferably 0.5% by mass, and further preferably 0.05 to 10% by mass.

When the joint function-improving composition of the present invention is an instant powder drink (powder) or an instant granular drink (granule), the active ingredient is contained in an amount of 0.1 to 80% by mass based on the dry mass. It is preferable that the content is 0.5 to 70% by mass, more preferably 1 to 60% by mass.

In order to exert the effect of the present invention more effectively, it is preferable that the active ingredient is contained in an amount of 80% by mass or more of the entire joint function-improving composition (excluding water) in terms of dry mass, and 90% by mass. % Or more is more preferable, 95% by mass or more is further preferable, and 100% by mass is particularly preferable. Further, when the composition for improving joint function of the present invention contains any of the components (a) to (f), the contained component is preferably composed only of the active ingredient of the present invention. That is, when the joint function-improving composition of the present invention contains, for example, the component (a) (plant material), it should be configured so as to contain no plant material other than barley, long-lived grass, kudzu, rice, maqui berry, and ginger. Is preferred.

The amount of the joint function-improving composition of the present invention to be taken is not particularly limited, but from the viewpoint of more significantly exerting the effects of the present invention, the amount of the active ingredient taken per day should be 500 mg/day or more. It is preferably ingested, more preferably 800 mg/day or more, even more preferably 1000 mg/day or more. The upper limit is not particularly limited, but is, for example, 5 g/day, preferably 4 g/day. The daily intake of glucosamine hydrochloride is preferably 500 to 4000 mg/day, more preferably 1000 to 3000 mg/day, and more preferably 1500 to 2500 mg/day. It is more preferable to ingest so as to be 1850 to 2250 mg/day, and it is particularly preferable to ingest to be 1850 to 2250 mg/day.

The joint function-improving composition of the present invention may be stored as one day in one container or divided into, for example, a plurality of containers such as 2-3 so that the daily intake becomes the above intake. it can.

The blending mass ratio of glucosamine and other components is preferably in the range of 0.5:1 to 70:1, and more preferably in the range of 0.75:1 to 60:1, in terms of dry mass. , 1:1 to 60:1, more preferably 1:1 to 50:1. When the compounding ratio of glucosamine and other components is within the above range, the effect of the present invention can be more effectively exhibited.

The joint function-improving composition of the present invention can be produced by a known method, if necessary, by adding components other than the active ingredient which is acceptable as an oral preparation or an external preparation.

Further, as the joint function improving composition as an oral preparation of the present invention, in addition to the joint function improving composition containing the active ingredient, the joint function improving composition obtained by adding the active ingredient to food (joint function improving composition Improved foods), for example, foods having an increased content of the active ingredient of the present invention as compared to ordinary foods (including natural foods) and foods not usually containing the active ingredient of the present invention. On the other hand, there may be mentioned foods to which active ingredients are added. The active ingredient may be added separately, simultaneously, or may be added together with other ingredients than the active ingredient.

Examples of the joint function improving food of the present invention include carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, smoothies, drinks such as green juice; frozen desserts such as ice cream, ice sorbet, shaved ice; buckwheat, udon, harusame, Chinese Noodles such as noodles and instant noodles; confectionery such as candy, candy, gum, chocolate, tablets, snacks, biscuits, jellies, jams, creams, baked goods, breads; processed fish and livestock products such as kamaboko, ham and sausage. Dairy products such as processed milk, fermented milk and yogurt; oils and fats such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing and processed foods; seasonings such as sauces and soy sauces; curry, stew, oyakodon , Porridge, porridge, Chinese rice bowl, bonito bowl, tempura bowl, beef bowl, hayashi rice, omelet rice, oden, marbo doff, dumplings, choux mai, hamburger, meatballs, various sauces, retort pouch foods such as various soups, etc. ..

The joint function improving method of the present invention is characterized by ingesting the above-described joint function improving composition of the present invention, but does not include medical treatment. The joint function-improving composition of the present invention is preferably taken by healthy people excluding sick people, and particularly preferably by elderly people having the above-mentioned troubles. Examples of the method of the present invention include a method of obtaining a joint function improving effect by providing the joint function improving food of the present invention in a restaurant such as a restaurant.

Hereinafter, the present invention will be described based on examples.
[Example 1]
(1) Chondrocytes (NHAc-kn) were prepared in 10% FBS-DMEM so as to be 5×10 ⁴ cells/mL, and 200 μL of each was seeded on a 96 well plate, and finally 1×10 ⁴ cells. /Well was adjusted.
(2) After preculture for 1 to 2 days, samples were added as follows. The concentration of each sample was adjusted to 4 times the desired final concentration.

In addition, about the sample (other components) insoluble in water, it melt|dissolved in DMSO and it adjusted so that it might become a 4-fold concentration sample in 1%DMSO-10%FBS-DMEM. Ca samples other than calcium chloride were dissolved in 1N HCl and then adjusted to be a 4-fold concentration sample in 1/50N HCl-10% FBS-DMEM. The IL1b solution was prepared by adjusting 10 μg/mL IL1b to 15 mL of 10% FBS-DMEM at a ratio of 2 μL. As glucosamine, commercially available glucosamine hydrochloride was used.

(3) About 18 hours after the addition of the sample, the cells were collected by CellAmp Direct RNA Prep Kit for RT-PCR (Takara). Then, the expression level of MMP3 was measured using One Step SYBR (registered trademark) PrimeScript ^™ RT-PCR Kit II. Note that RPLP0 was also measured as an internal standard. When the MMP-3 expression level is high, it indicates that the destruction of articular chondrocytes is progressing, and when the MMP-3 expression level is low, the destruction of the articular chondrocytes is suppressed and the articular chondrocytes are protected. It is understood that it is done.

The results are shown in Tables 4 to 10 and FIGS. 1 to 13.

In each figure, from the left, “control”, “IL1b addition”, “single addition of glucosamine (for IL1b addition)”, “single addition of other components (for IL1b addition)”, “glucosamine+(other for IL1b addition)” The result of "component addition" is shown. Further, the numerical values in the description below the graph indicate the sample concentration, and for example, “G — 100” in the upper left graph of FIG. 1 indicates glucosamine 100 (μg/mL). The concentration unit of the added component is μg/mL in all graphs.

As for barley, a dry ground powder of young leaves was used.
For long-lived grass, finely ground powder of fresh leaves was used.
For kudzu, a hot water extract of flowers (dry powder) was used.
About rice bran, the commercial item was used.
For maki berries, a commercial dry fruit powder was used.
For red ginger (Zingiber officinale var. Rubra), a hot water extract of rhizome (dry powder) was used.
For ginger (Zingiber officinale), a hot water extract of rhizome (dry powder) was used.
For lemon verbena, dry ground leaves were used.

As shown in Tables 4 to 10 and FIGS. 1 to 13, the combination of glucosamine and the specific other component of the present invention synergistically reduced the expression level of MMP-3. Therefore, according to the composition for improving joint function of the present invention, inflammation can be suppressed, joint chondrocytes can be protected (the destruction of articular chondrocytes can be suppressed), and joint pain can be more effectively improved.

[Example 2] (Production of tablets)
A tablet (3000 mg of 6 tablets) composed of the following ingredients was produced.

Glucosamine hydrochloride 2000mg
Proteoglycan 5 mg
Fossil Coral Ca 150mg
Calcium stearate 50mg
β-carotene 10 mg
Vitamin B1 5mg
Vitamin B2 5 mg
Vitamin B12 5 mg
Vitamin D3 2.5mg
Long-lived grass powder 300mg
Proline 30 mg
Crystalline cellulose 50mg
Sucrose fatty acid ester 30mg
Maltose balance

The above tablets may be taken by chewing 6 tablets 2 to 3 times a day by chewing or without chewing with water.

[Example 3] (Production of capsule)
The following mixture was enclosed in a soft capsule to produce 6 capsules.

Glucosamine hydrochloride 1500mg
Proteoglycan 5 mg
Rice bran extract 20mg
Maki berry powder 100mg
Shell-baked Ca 120mg
Vitamin E 30mg
Niacin 5mg
Chlorogenic acid 10mg
20 mg of proline
Selenium 5 mg
Sodium pantothenate 10mg
Maltose balance

The above tablets are divided into 6 tablets 2 to 3 times a day and taken with water.

[Example 4] (Production of granules)
The following ingredients were mixed to prepare a granule (3000 mg) by a conventional method.

Glucosamine hydrochloride 1800mg
Proteoglycan 5 mg
Unbaked Ca 200 mg
Sucrose fatty acid ester 50mg
Selenium 5 mg
Vitamin E 50mg
Barley young leaf powder 800 mg
Niacin 10mg
Biotin 10 mg
Proline 5 mg
Remainder of starch

[Example 5] (Production of instant powder)
The following components were mixed to prepare instant powder (6 g) by a conventional method.

Glucosamine hydrochloride 2500mg
Proteoglycan 5 mg
Unbaked Ca 200 mg
Barley young leaf powder 1000mg
Long-life grass powder 500mg
250 g of ginger powder
Selenium 5 mg
Vitamin E 300mg
Vitamin K 200mg
Niacin 50mg
Biotin 50 mg
Proline 30 mg
Valine 30mg
Leucine 20mg
Isoleucine 20 mg
Aspartame 300mg
Oligosaccharide 500mg
Dextrin balance

[Example 6] (Production of liquid agent)
A liquid agent (50 mL) composed of the following components was produced.

Glucosamine hydrochloride 2000mg
Type II collagen 25mg
Milk Ca 200mg
800 mg aspartame
Red ginger extract 300mg
Ginger extract 200mg
Katsura flower extract 150mg
Proline 100 mg
50 mg of asparagine
Valine 25mg
Leucine 20mg
Isoleucine 20mg
Gallic acid 10mg
Vitamin C 5mg
Fragrance appropriate amount of water balance

The composition of the present invention has a high effect of improving joint function and can be used as an oral preparation or an external preparation, so that the industrial utility of the present invention is high.

Claims (3)

A composition comprising glucosamine and maqui berry. A composition containing glucosamine and maki berry , which has a cartilage protective action. The composition according to claim 2, which is a joint function-improving agent having a cartilage-protecting action (except for improvement of non-inflammatory joint pain).