WO2012035685A1

WO2012035685A1 - Composition for promoting hyaluronic acid production

Info

Publication number: WO2012035685A1
Application number: PCT/JP2011/003350
Authority: WO
Inventors: 喜則関口; 美智子奥野; 長岡　功; 庸五十嵐
Original assignee: 磐田化学工業株式会社; 学校法人順天堂
Priority date: 2010-09-13
Filing date: 2011-06-13
Publication date: 2012-03-22
Also published as: JPWO2012035685A1

Abstract

A novel composition having strong hyaluronic acid production-promoting capability is provided. The present invention provides a composition for promoting hyaluronic acid production that comprises S-adenosylmethionine and phytic acid. The inventors solved this issue on the basis of the unexpected discovery that a composition comprising S-adenosylmethionine and phytic acid promotes hyaluronic acid production. The inventors confirmed that hyaluronic acid production is promoted by a composition that comprises S-adenosylmethionine and phytic acid, regardless of the fact that none of the components of S-adenosylmethionine and phytic acid promote hyaluronic acid production.

Description

Hyaluronic acid production promoting composition

The present invention relates to a hyaluronic acid production promoter. More specifically, the present invention relates to a hyaluronic acid production promoter containing S-adenosylmethionine, phytic acid and cyclodextrin.

Hyaluronic acid is a linear high-molecular polysaccharide having a disaccharide repeating unit in which β-DN-acetylglucosamine (GlcNAc) and β-D-glucuronic acid are linked by β1 → 3. Hyaluronic acid, together with chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, and keratan sulfate, is a type of glycosaminoglycan, but unlike other glycosaminoglycans, it has no sulfate group and is covalently bound to proteins. The existence of the body is not known. Hyaluronic acid exhibits polydispersity in terms of molecular weight, but other than that, no structural heterogeneity is known, and there is no species specificity and organ specificity. Cartilage proteoglycans form huge aggregates around hyaluronic acid. Hyaluronic acid constitutes an extracellular matrix together with collagen, fibronectin, and proteoglycan. Furthermore, hyaluronic acid is also known to control cell adhesion and cell migration through specific receptors.

The human joint capsule is composed of an outer fiber layer and an inner synovial layer. The synovial fluid contained in the synovium contains hyaluronic acid and glycoprotein, and these two components act to lubricate the joint. When osteoarthritis develops, the production of hyaluronic acid that exerts a lubricating action in the joint decreases, the destruction by the enzyme increases, and the amount of hyaluronic acid in the joint decreases. As hyaluronic acid in the joint decreases, it becomes difficult to absorb and disperse external impacts in the joint. Therefore, a method for relieving arthritis by injecting hyaluronic acid into the joint was approved by the US FDA in 1997 and is still being treated. However, such a method is effective in that temporary improvement of joint function can be expected, but is highly invasive and painful because it requires regular intra-articular injection.

Further, it has been reported that 50% or more of hyaluronic acid existing in the living body of mammals is distributed in the skin, particularly between cells of the epidermis and in connective tissue of the dermis. The amount of hyaluronic acid in human skin decreases with aging. It is believed that the decrease in hyaluronic acid content in the skin is one of the direct causes of the decrease in skin elasticity and moisture content associated with aging.

For the purpose of supplying hyaluronic acid to joints and skin, attempts have been made to administer hyaluronic acid externally or orally. However, since hyaluronic acid is present in the tissue, it is not taken into the tissue as it is even if it is administered transdermally, and is orally absorbed only in a degraded state in the digestive tract, so transdermal administration of hyaluronic acid Or the effect of oral administration was only limited.

S-adenosylmethionine is known to have a significant therapeutic effect on osteoarthritis. For example, Non-Patent Document 1 describes the results of a comparative study of the therapeutic effect of S-adenosylmethionine on osteoarthritis with placebo and non-steroidal anti-inflammatory agents in terms of pain relief, functional recovery, and side effects. ing. As a result, S-adenosylmethionine had the same therapeutic effect as non-steroidal anti-inflammatory drugs in reducing pain and restoring function. It has been suggested that the various effects of S-adenosylmethionine in arthropathy are due to the promotion of proteoglycan production by S-adenosylmethionine (Non-patent Documents 2 and 3). The relationship between S-adenosylmethionine and hyaluronic acid production was not known.

Also for phytic acid, the relationship with hyaluronic acid production was not known.

An object of the present invention is to provide a novel composition having a remarkable hyaluronic acid production promoting ability.

The present inventors have unexpectedly discovered that a composition containing S-adenosylmethionine and phytic acid promotes hyaluronic acid production, and based on this, the above problems have been solved. The present inventors have promoted hyaluronic acid production by a composition comprising S-adenosylmethionine and phytic acid, even though each component of S-adenosylmethionine and phytic acid does not promote hyaluronic acid production at all. Proved to be. By using the composition of the present invention as a health food (supplement), a pharmaceutical product or an external preparation for skin (cosmetics, etc.), or adding or blending the composition of the present invention as a food additive or food supplement to food Prevents, reduces or improves arthropathy, removes or reduces pain related to arthropathy, maintains skin firmness and moisture, improves wrinkles, tarmi, spots, kusumi, dry skin or sunburn skin, prevents skin aging symptoms Or, in the improvement, an excellent effect can be provided.

Therefore, in a representative embodiment, the present invention provides a composition for promoting hyaluronic acid production, comprising S-adenosylmethionine and phytic acid.

In one aspect, the composition further comprises cyclodextrin.

In another aspect, the cyclodextrin is γ-cyclodextrin.

In another aspect, the composition further comprises yeast.

In one aspect, the composition is a composition for the treatment of arthropathy.

In another embodiment, the present invention provides a cosmetic improving composition comprising S-adenosylmethionine and phytic acid.

In one aspect, the composition further comprises cyclodextrin.

In another aspect, the cyclodextrin is γ-cyclodextrin.

In another aspect, the composition further comprises yeast.

In one aspect, the composition is a cosmetic.

In another embodiment, the present invention provides a method for producing a composition for promoting hyaluronic acid production,
There is provided a production method comprising a step of culturing yeast to produce S-adenosylmethionine, and a step of adding phytic acid to a culture solution of the yeast.

In one aspect, the method further includes a step of adding cyclodextrin to the culture solution.

In another aspect, the cyclodextrin is γ-cyclodextrin.

In another aspect, in the above method, the cyclodextrin is added to the culture solution after the addition of the phytic acid.

In another aspect, the culture solution is a bacterial cell concentrate.

In another aspect, the pH of the culture solution after addition of the phytic acid is 3 or less.

In another aspect, the method further includes a step of drying the culture solution.

In another embodiment, the present invention relates to a method for producing a beauty improving composition,
There is provided a production method comprising a step of culturing yeast to produce S-adenosylmethionine, and a step of adding phytic acid to a culture solution of the yeast.

In another aspect, the cyclodextrin is γ-cyclodextrin.

In another aspect, the culture solution is a bacterial cell concentrate.

In one aspect, the composition is a cosmetic.

According to the present invention, a novel composition having a remarkable ability to promote hyaluronic acid production is provided.

FIG. 1 shows a yeast composition containing S-adenosylmethionine, phytic acid and γ-cyclodextrin without adding a substance capable of promoting hyaluronic acid production (Data 1), adding glucosamine (Data 2) It is a graph which shows the amount of hyaluronic acid production of a human chondrocyte cell line (SW1353) at the time of adding (data 3) and culture | cultivating. FIG. 2 shows a yeast composition containing S-adenosylmethionine, phytic acid and γ-cyclodextrin without adding a substance capable of promoting hyaluronic acid production (Data 1), adding glucosamine (Data 2) It is a graph which shows the hyaluronic acid production amount of a human synovial cell line (MH7A) at the time of adding (data 3) and culture | cultivating. FIG. 3 is a graph showing the amount of hyaluronic acid produced by the human chondrocyte cell line (SW1353) when cultured under the following conditions. Data 1: No substance having the ability to promote hyaluronic acid production was added. Data 2: only yeast added (no S-adenosylmethionine or phytic acid). Data 3: S-adenosylmethionine, phytic acid and γ-cyclodextrin-containing yeast composition added. Data 4: only S-adenosylmethionine added. Data 5: Only γ-cyclodextrin was added. Data 6: Only phytic acid was added. Data 7: Yeast and S-adenosylmethionine added. Data 8; phytic acid and S-adenosylmethionine added. Data 9; γ-cyclodextrin and S-adenosylmethionine added. FIG. 4 is a graph showing the amount of hyaluronic acid produced by a human dermal fibroblast cell line when cultured under the following conditions. Data 1: No substance having the ability to promote hyaluronic acid production was added. Data 2: 0.50 μg / mL S-adenosylmethionine and 1.25 μg / mL phytic acid added. Data 3: Add 1.00 μg / mL S-adenosylmethionine and 2.50 μg / mL phytic acid. Data 4: 10.00 μg / mL S-adenosylmethionine and 25.00 μg / mL phytic acid added. Data 5: S-adenosylmethionine, phytic acid and γ-cyclodextrin-containing yeast composition (0.005 w / w%) corresponding to an S-adenosylmethionine amount of 0.50 μg / mL was added. Data 6: S-adenosylmethionine, phytic acid and γ-cyclodextrin-containing yeast composition (0.010 w / w%) corresponding to an S-adenosylmethionine amount of 1.00 μg / mL was added. Data 7: S-adenosylmethionine, phytic acid and γ-cyclodextrin-containing yeast composition (0.100 w / w%) corresponding to an S-adenosylmethionine amount of 10.00 μg / mL was added. Data 8: Addition of 0.005 w / w% yeast mixture (without S-adenosylmethionine) containing phytic acid (1.25 μg / mL) and γ-cyclodextrin (2.00 μg / mL). Data 9: Add 0.010 w / w% yeast mixture (without S-adenosylmethionine) containing phytic acid (2.50 μg / mL) and γ-cyclodextrin (4.00 μg / mL). Data 10: Addition of 0.100 w / w% yeast mixture (without S-adenosylmethionine) containing phytic acid (25.00 μg / mL) and γ-cyclodextrin (40.00 μg / mL).

Hereinafter, the present invention will be described by way of example with reference to the accompanying drawings as necessary. The terms used in this specification are used in the meaning normally used in the art unless otherwise specified. Thus, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification will prevail.

(Definition)
As used herein, “S-adenosylmethionine” is also referred to as active methionine, methionyl adenosine, and is abbreviated as “SAMe” or “AdoMet”, and has the molecular formula C ₁₅ H ₂₃ N ₆ O ₅ S (average molecular weight 399). .447).

“Phytic acid” in the present specification is a kind of biological material represented by the molecular formula C ₆ H ₁₈ O ₂₄ P ₆ and is a 6-phosphate ester of myo-inositol. myo-inositol-1,2,3,4,5,6-6 phosphoric acid, myo-inositol-1,2,3,4,5,6-hexaphosphate, or hexakis phosphate or hexakis (phosphorus) also referred to as dihydrogen), abbreviated as IP _6.

As used herein, “cyclodextrin” refers to any cyclic oligosaccharide in which several molecules of glucose are bound in a cyclic manner. As cyclodextrins, those in which 5 or more glucoses are bonded are well known, and as a general one, α-cyclodextrin having a molecular weight of 973 (cyclodextrin) (cyclohexaamylose) having 6 glucoses bonded thereto is well known. 7-linked β-cyclodextrin (cyclodextrin) (cycloheptaamylose) having a molecular weight of 1135, and 8 linked γ-cyclodextrin (cyclodextrin) (cyclooctaamylose) having a molecular weight of 1297. The “cyclodextrin” in the present invention is not particularly limited to those having these polymerization degrees, and refers to glucose-linked cyclic oligosaccharides having any polymerization degree. The “cyclodextrin” in the present invention may be branched or unbranched.

As used herein, “hyaluronic acid” refers to a linear high-molecular polysaccharide having a disaccharide repeating unit in which β-DN-acetylglucosamine (GlcNAc) and β-D-glucuronic acid are linked by β1 → 3. The hyaluronic acid in the present invention is not limited to a specific molecular weight. The hyaluronic acid of the present invention is an extracellular matrix of almost all tissues, but includes hyaluronic acid produced by any hyaluronic acid-producing cells such as chondrocytes, synovial cells, fibroblasts, etc. .

As used herein, “hyaluronic acid production” refers to the production of hyaluronic acid at an arbitrary site or an arbitrary cell. Such sites include, but are not limited to, joints, cartilage, skin (face, hands, scalp, neck, etc.). Such cells include, but are not limited to, chondrocytes, synoviocytes, fibroblasts and the like.

In the present specification, when the amount of hyaluronic acid produced by the hyaluronic acid-producing cells in the presence of the substance is significantly increased compared to the amount of hyaluronic acid produced by the hyaluronic acid-producing cells in the absence of the substance, Hyaluronic acid production is said to be “promoted”. Examples of the hyaluronic acid-producing cells include, but are not limited to, chondrocytes, synoviocytes, fibroblasts and the like. As described below, methods for measuring the amount of hyaluronic acid produced by hyaluronic acid-producing cells are well known to those skilled in the art. For example, commercially available kits and the like (for example, hyaluronic acid measuring kits sold by Seikagaku Biobusiness Co., Ltd.) ).

When the amount of hyaluronic acid produced in the presence of the substance increases by a certain percentage relative to the amount of hyaluronic acid produced in the absence of the substance, it is said to “accelerate hyaluronic acid production by ~%”. For example, when the amount of hyaluronic acid produced in the presence of the composition of the present invention is increased by 50% relative to the amount of hyaluronic acid produced in the absence of the composition of the present invention, the composition of the present invention becomes “hyaluronic acid”. It promotes acid production by 50%. "

In this specification, when a substance promotes hyaluronic acid production by at least 10%, the substance is said to have “hyaluronic acid production promoting ability”.

As used herein, “yeast” refers to any yeast that can be taken orally. The yeast in the present invention may be in any form including, but not limited to, powders, pastes, suspensions, freeze-dried products and the like.

“Beauty improvement” in the present specification refers to the maintenance of skin firmness and moisture, improvement of wrinkles, tarmi, stains, kusumi, dry skin or sunburn skin, and prevention or improvement of skin aging symptoms.

(Preferred embodiment)
The present inventors have promoted hyaluronic acid production by a composition comprising S-adenosylmethionine and phytic acid, even though each component of S-adenosylmethionine and phytic acid does not promote hyaluronic acid production at all. Proved to be. By using the composition of the present invention as a health food (supplement), a pharmaceutical product or an external preparation for skin, or by adding or blending the composition of the present invention into a food as a food additive or food supplement, arthropathy Prevention, reduction or improvement of pain, removal or reduction of pain related to arthropathy, maintenance of skin firmness and moisture, improvement of wrinkles, tarmi, stains, kusumi, dry skin or sunburn skin, prevention or improvement of skin aging symptoms, An excellent effect can be provided.

(Composition of the present invention)
The composition of the present invention contains 0.5 to 5 moles of phytic acid per mole of S-adenosylmethionine. More preferably, it contains 1.5 to 2.5 moles of phytic acid per mole of S-adenosylmethionine. When the composition of the present invention contains S-adenosylmethionine and phytic acid in an amount within this range, the desired hyaluronic acid production promoting effect and cosmetic improvement effect are exhibited.

The composition of the present invention can contain not only S-adenosylmethionine and phytic acid, but also any other component such as an excipient or additive. In certain embodiments, the composition of the present invention further comprises cyclodextrin in addition to S-adenosylmethionine and phytic acid. Preferably, the composition of the present invention contains 0.5 to 5 moles of cyclodextrin per mole of S-adenosylmethionine. More preferably, 1 to 2 mol of cyclodextrin is contained per 1 mol of S-adenosylmethionine. The composition of the present invention contains S-adenosylmethionine, phytic acid, and cyclodextrin in an amount within this range, thereby providing the desired hyaluronic acid production promoting effect and cosmetic improvement effect, and usually the unstable S -Adenosylmethionine is remarkably stabilized and the storage stability of the composition of the invention is dramatically improved.

In a preferred embodiment, the cyclodextrin contained in the composition of the present invention is γ-cyclodextrin. Preferably, the composition of the present invention contains 0.5 to 5 moles of γ-cyclodextrin per mole of S-adenosylmethionine. More preferably, it contains 1 to 2 mol of γ-cyclodextrin per 1 mol of S-adenosylmethionine. The storage stability of the composition of the present invention is improved by adding cyclodextrin, but the improvement in stability is particularly remarkable in γ-cyclodextrin.

In a preferred embodiment, the composition of the present invention is a composition further comprising yeast in addition to S-adenosylmethionine, phytic acid and cyclodextrin. This yeast may have S-adenosylmethionine-producing ability and / or contain S-adenosylmethionine in cells. In a preferred embodiment, the S-adenosylmethionine in the composition of the present invention is that produced by yeast. The yeast in the present invention includes any yeast that can be taken orally, and Saccharomyces cerevisiae is particularly preferable. S-adenosylmethionine-producing yeast is cultured to produce S-adenosylmethionine, to which phytic acid and other ingredients such as γ-cyclodextrin are added, and S-adenosine is added. A composition comprising silmethionine, phytic acid, cyclodextrin and yeast can be obtained. The composition containing S-adenosylmethionine, phytic acid, cyclodextrin and yeast may be used in any form, but is typically in the form of a paste or powder. Preferably, the composition comprising S-adenosylmethionine, phytic acid, cyclodextrin and yeast is in powder form.

As described in the following examples, it was demonstrated that the combination of S-adenosylmethionine and phytic acid has a hyaluronic acid production promoting effect. Accordingly, the composition of the present invention comprises a combination of S-adenosylmethionine and phytic acid. The composition of the present invention may comprise yeast in addition to S-adenosylmethionine and phytic acid. More preferably, the composition of the present invention further comprises a cyclodextrin, particularly γ-cyclodextrin. This is because the storage stability of S-adenosylmethionine is remarkably improved by the combination of phytic acid and γ-cyclodextrin (see Japanese Patent Application Laid-Open No. 2010-18596). Thus, the composition of the present invention may comprise yeast in addition to S-adenosylmethionine, phytic acid and cyclodextrin (preferably γ-cyclodextrin).

(Production of the composition of the present invention)
In a preferred embodiment, the composition of the present invention is produced by culturing a yeast capable of producing S-adenosylmethionine, producing S-adenosylmethionine, and adding phytic acid to the yeast. This yeast is preferably the yeast Saccharomyces cerevisiae K-7 strain (Sake Yeast Association No. 7). Addition of phytic acid to the yeast may be performed during the culture of the yeast, or may be performed after the culture. Preferably, after the yeast is cultured to produce S-adenosylmethionine, the culture solution is removed to obtain a yeast cell concentrate, and phytic acid is added to the concentrate. This yeast cell concentrate is obtained by centrifuging the culture (for example, 8,000 rpm), removing the supernatant, collecting the cells, and adding an appropriate amount of the supernatant removed to the collected cells, It can be prepared by preparing a bacterial cell concentrate.

In certain embodiments, after adding phytic acid to a concentrate containing yeast that produced S-adenosylmethionine, the mixture may be dried. Examples of the drying method include, but are not limited to, freeze drying, spray drying, and reduced pressure drying. As the drying method in the present invention, freeze-drying is preferred. In certain embodiments, the mixture can be dried at −80 ° C. overnight and lyophilized for 72 h.

The carbon source used when culturing the yeast is not particularly limited as long as the yeast can assimilate, for example, carbohydrates such as glucose, sucrose, starch, and molasses, alcohols such as ethanol, acetic acid, etc. The organic acid is mentioned. The nitrogen source is not particularly limited as long as the yeast to be used can assimilate, and includes, for example, inorganic nitrogen compounds such as ammonia, nitric acid, urea, or organic nitrogen compounds such as yeast extract and malt extract. Can be mentioned. Moreover, as inorganic salts, salts of phosphoric acid, potassium, sodium, magnesium, calcium, iron, zinc, manganese, cobalt, copper, molybdenum and the like can be used. Further, methionine, adenine, and adenosylribonucleoside constituting the skeleton of S-adenosylmethionine can be added and cultured.

The cultivation of S-adenosylmethionine-producing yeast in the present invention can be carried out under either anaerobic conditions or aerobic conditions, but aerobic conditions are preferred in order to efficiently grow yeast cells. The culture temperature of the S-adenosylmethionine-producing yeast in the present invention is an arbitrary temperature within the range in which the yeast can grow, but is preferably cultured in the range of 15 to 40 ° C, more preferably in the range of 25 to 35 ° C. . The pH during the culture of the S-adenosylmethionine-producing yeast in the present invention is an arbitrary pH within the range in which the yeast can grow, but the culture in the range of pH 3.5 to 8.0 is preferable, and pH 4.0 to A range of 6.5 is more preferred. In addition, the culture method and culture conditions for S-adenosylmethionine-producing yeast in the present invention can be appropriately determined by those skilled in the art according to general yeast culture methods or culture conditions. In a specific embodiment, the yeast is a 5 L jar fermenter (feed medium amount: 3 L), the culture temperature is 28 ° C., the stirring speed is 500 rpm, the culture time is 36-48 h, the aeration rate is 0.5 VVM, the medium composition (w / 100 mL): cultured under conditions of 5% glucose, 0.75% yeast extract, 2.0% peptone, and 0.15% methionine.

In a preferred embodiment, the composition of the present invention is produced by culturing a yeast capable of producing S-adenosylmethionine to produce S-adenosylmethionine, and adding phytic acid and cyclodextrin to the yeast. The Addition of phytic acid and cyclodextrin to yeast may be performed during yeast culture or after yeast culture. Addition of phytic acid to the yeast may be performed during the culture of the yeast, or may be performed after the culture. Preferably, after culturing yeast to produce S-adenosylmethionine, the culture solution is removed to obtain a concentrated yeast cell concentrate, and phytic acid and cyclodextrin are added to the concentrated solution. In certain embodiments, after adding phytic acid and cyclodextrin to a concentrate containing yeast that produced S-adenosylmethionine, the mixture may be dried. Examples of the drying method include, but are not limited to, freeze drying, spray drying, and reduced pressure drying. As the drying method in the present invention, freeze-drying is preferred.

The phytic acid and cyclodextrin may be added after the phytic acid is added first and then the cyclodextrin may be added, or after the cyclodextrin is added first and the phytic acid may be added simultaneously. May be. In a preferred embodiment of the invention, phytic acid is first added to the yeast or yeast concentrate and then cyclodextrin is added. Without wishing to be bound by theory, the addition of phytic acid and cyclodextrin in this order allows the phytic acid-S-adenosylmethionine complex formed by electrostatic interaction to be cyclodextrin. Cover and form aggregates so that significant stabilization of the unstable S-adenosylmethionine can be achieved.

In a specific embodiment, in the production of the composition of the present invention, the pH of the yeast culture solution (or yeast cell concentrate) after addition of phytic acid is 3 or less. In an exemplary embodiment, this pH of 3 or less is achieved by the addition of phytic acid to the yeast culture (or yeast cell concentrate). In another embodiment, pH can be adjusted in addition to the addition of phytic acid. The method of adjusting the pH is well known to those skilled in the art, and can be performed, for example, by adding citric acid. Without wishing to be bound by theory, when phytic acid is added at a low pH of 4 or less, S-adenosylmethionine and phytic acid do not form a salt but bind via a cation. Conceivable.

(Hyaluronic acid production)
For example, the amount of hyaluronic acid produced by human chondrocytes can be measured as follows.

Human chondrocyte cell line (SW1353) is cultured and maintained at 37 ° C. in Leibovitz's L-15 medium containing 10% fetal bovine serum and antibiotics. For example, the cells are seeded in a 12-well plate in an amount of 1.5 × 10 ⁵ cells per well and pre-cultured overnight. Thereafter, an additive to be tested for hyaluronic acid production ability is added and incubated for 24 hours. Next, the culture supernatant is collected, and the amount of hyaluronic acid contained in the culture supernatant is measured using a commercially available kit or the like (for example, a hyaluronic acid measurement kit sold by Seikagaku Biobusiness Co., Ltd. (Tokyo)). . This amount of hyaluronic acid is compared with the amount of hyaluronic acid when no additive is added.

The amount of hyaluronic acid produced by synovial cells can be measured as follows.

Human synovial cell culture cell line (MH7A) is cultured and maintained at 37 ° C. in RPMI-1640 medium containing 10% fetal bovine serum and antibiotics under 5% CO ₂ . For example, the cells are seeded in a 12-well plate in an amount of 1.0 × 10 ⁵ cells per well and pre-cultured overnight. Thereafter, an additive to be tested for hyaluronic acid production ability is added and incubated for 24 hours. Next, the culture supernatant is collected, and the amount of hyaluronic acid contained in the culture supernatant is measured using a commercially available kit or the like (for example, a hyaluronic acid measurement kit sold by Seikagaku Biobusiness Co., Ltd.). This amount of hyaluronic acid is compared with the amount of hyaluronic acid when no additive is added.

For example, the amount of hyaluronic acid produced by dermal fibroblasts can be measured as follows.

Normal human skin fibroblast cell line (NHDF), 2% fetal bovine serum, heparin 10 μg / ml, hydrocortisone 1 μg / ml, human recombinant epidermal growth factor 10 ng / ml, human recombinant basic fibroblast growth Cultivation in basal medium Medium106S containing 3 ng / ml of factor at 37 ° C. under 5% CO ₂ , for example, in an amount of 5.0 × 10 ⁴ cells per well, this cell was placed in a 24-well microplate. Sowing. At the time of seeding, the same medium was used and cultured until the cells became confluent. Then, 2% fetal bovine serum to which an additive for testing hyaluronic acid production ability was added, heparin 10 μg / ml, hydrocortisone 1 μg / ml, ascorbic acid 2-phosphorus The medium is replaced with Medium 106S containing 100 μM magnesium acid and further cultured for 48 hours. Next, the culture supernatant is collected, and the amount of hyaluronic acid contained in the culture supernatant is measured using a commercially available kit or the like (for example, a hyaluronic acid measurement kit sold by Seikagaku Biobusiness Co., Ltd.). This amount of hyaluronic acid is compared with the amount of hyaluronic acid when no additive is added.

The composition of the present invention promotes hyaluronic acid production by 10%, 15%, 20%, 25%, 30%, 25%, 40%, 45%, 50% or more. In a preferred embodiment, the composition of the present invention promotes hyaluronic acid production by 30% or more, and in a more preferred embodiment, the composition of the present invention promotes hyaluronic acid production by 45% or more.

The composition of the present invention promotes hyaluronic acid production in chondrocytes by 10%, 15%, 20%, 25%, 30%, 25%, 40%, 45%, 50% or more. In a preferred embodiment, the composition of the present invention promotes hyaluronic acid production in chondrocytes by 30% or more, and in a more preferred embodiment, the composition of the present invention promotes hyaluronic acid production in chondrocytes by 45% or more. To do.

The composition of the present invention promotes hyaluronic acid production in synoviocytes by 10%, 15%, 20%, 25%, 30%, 25%, 40%, 45%, 50% or more. In a preferred embodiment, the composition of the present invention promotes hyaluronic acid production in synoviocytes by 30% or more, and in a more preferred embodiment, the composition of the present invention enhances hyaluronic acid production in synoviocytes by 45%. Promote more.

The composition of the present invention promotes hyaluronic acid production in dermal fibroblasts by 10%, 15%, 20%, 25%, 30%, 25%, 40%, 45%, 50% or more. In a preferred embodiment, the composition of the present invention promotes hyaluronic acid production in skin fibroblasts by 30% or more, and in a more preferred embodiment, the composition of the present invention enhances hyaluronic acid production in skin fibroblasts. Promote 45% or more.

(Beauty improvement)
The composition of the present invention not only promotes hyaluronic acid production by chondrocytes and synoviocytes but can also promote hyaluronic acid production by skin cells. The composition of the present invention promotes hyaluronic acid production by skin cells (including epidermal fibroblasts, dermal fibroblasts, etc.), thereby maintaining skin firmness and moisture, wrinkles, tarmi, stains, kusumi, dryness. An excellent effect can be provided in improving the skin or tanned skin, and preventing or improving skin aging symptoms.

(Application of the composition of the present invention)
The composition of the present invention can be a food composition, a pharmaceutical product (including quasi-drugs), an external preparation for skin (including cosmetics), and the like.

The food of the composition of the present invention (hereinafter referred to as the food composition of the present invention) is a health food (a food for specified health use, a nutritional functional food), a supplement (a dietary supplement), a food additive or a food supplement. Etc. Typically, the food composition of the present invention is a powder obtained by drying a composition containing S-adenosylmethionine, yeast producing it, phytic acid, and optionally other components (especially cyclodextrin). It is what. The powdered food composition of the present invention may be ingested as a food additive or food supplement added to other foods, or the powdered food composition of the present invention itself may be a health food or a supplement. As may be taken alone. The composition of the present invention may be processed into pellets, tablets, granules, etc. together with excipients such as dextrin, lactose, starch and the like, fragrances, pigments, etc., as necessary, and coated with gelatin or the like to be processed into capsules. May be. The composition of the present invention is particularly suitable for use as a health food or supplement. Typically, the food composition of the present invention comprises about 3 g or more S-adenosylmethionine per 100 g.

The amount of S-adenosylmethionine or phytic acid or the like in the food composition of the present invention is difficult to define uniformly depending on the type and condition of the food, but the S-adenosylmethionine content is 10 to 5000 mg / meal. 100 to 1000 mg / meal, preferably about 10 to 100% (preferably 30 to 100%, more preferably 50 to 100%, even more preferably 80 to 100%) in the case of supplements, beverages Or in the case of a general food etc., it may be about 0.01% or less.

The food composition of the present invention is blended with excipients or additives usually used in foods, and tablets, tablets, pills, granules, powders, powders, capsules, wettable powders, emulsions, liquids, It can also be prepared into a dosage form such as an extract or an elixir. Common excipients used in food include syrup, gum arabic, sucrose, lactose, powdered reduced maltose, cellulose sugar, mannitol, maltitol, dextran, starches, gelatin, sorbit, tragacanth, polyvinylpyrrolidone Agents; sucrose fatty acid esters, glycerin fatty acid esters, magnesium stearate, calcium stearate, talc, polyethylene glycol, etc .; disintegrants such as potato starch; wetting agents such as sodium lauryl sulfate. Examples of additives include fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, and the like.

The formulation of the composition of the present invention into a pharmaceutical product (hereinafter referred to as the pharmaceutical product of the present invention) can be an oral administration formulation. Examples of solid preparations include powders, granules, tablets, tablets, pills, capsules, chewable agents, and the like, and examples of liquid preparations include emulsions, solutions, syrups and the like. The medicament of the present invention contains about 3 g or more of S-adenosylmethionine per 100 g.

A solid preparation can be prepared by blending a pharmaceutically acceptable carrier or additive with S-adenosylmethionine and phytic acid of the present invention, which are the active ingredients, and yeast, cyclodextrin and the like as necessary. . For example, excipients such as sucrose, lactose, glucose, starch, mannitol; binders such as gum arabic, gelatin, crystalline cellulose, hydroxypropylcellulose, methylcellulose; disintegrants such as carmellose, starch; anhydrous citric acid Stabilizers such as sodium laurate, glycerol and the like can be formulated for the formulation of the medicament of the present invention. Furthermore, the medicament of the present invention may be coated or encapsulated with gelatin, sucrose, gum arabic, carnauba wax and the like. In addition, the liquid preparation contains, for example, the S-adenosylmethionine and phytic acid of the present invention, which are active ingredients, and, if necessary, yeast, cyclodextrin, etc. in water, ethanol, glycerin, syrup, or a mixture thereof. It can be prepared by dissolving or dispersing. Additives such as sweeteners, preservatives, demulcents, lubricants, diluents, buffers, or colorants may be further added to the medicament of the present invention.

(Skin external preparation)
A composition obtained by formulating the composition of the present invention into a skin external preparation (hereinafter referred to as the skin external preparation of the present invention) can typically be a cosmetic. The dosage form of the external preparation for skin of the present invention is not particularly limited. For cosmetics, for example, lotion, cosmetic emulsion, cosmetic cream, cosmetic gel, cosmetic liquid, pack agent, foundation, lipstick, lip balm, Examples include skin care products or makeup products such as lip gloss, facial cleansers, body soaps, hand creams, shampoos, rinses, hair styling products, and the like. The external preparation for skin of the present invention contains about 3 g or more of S-adenosylmethionine per 100 g.

In addition to the composition of the present invention, the external preparation for skin of the present invention contains components usually used in cosmetics, such as purified water, alcohols (lower alcohols, polyhydric alcohols, etc.), fats and oils, waxes, hydrocarbons. And a base, such as surfactants, thickeners, UV absorbers, UV scattering agents, stabilizers, preservatives, colorants, and fragrances, if necessary. be able to.

If it is an external preparation for skin as a medicine or quasi-drug, an ointment, gel, liniment, lotion, emulsion, powder, suspension, aerosol, liquid, etc. And dosage forms such as plasters, plasters, tapes, plasters, and the like.

A skin preparation for external use as a medicine or quasi-drug can be prepared by blending the composition of the present invention with an appropriate base. Bases include sodium alginate, gelatin, corn starch, tragacanth gum, methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, xanthan gum, carrageenan, mannan, agarose, dextrin, carboxymethyl starch, polyvinyl alcohol, sodium polyacrylate, methoxyethylene-maleic anhydride Polymers such as copolymer, polyvinyl ether, polyvinyl pyrrolidone, carboxyvinyl polymer, hydroxypropylcellulose, hydroxypropylmethylcellulose, pullulan; hydrocarbons such as white petrolatum, yellow petrolatum, paraffin, ceresin wax, microcrystalline wax; stearic acid Higher fatty acids such as cetanol, octyldodecanol, stearyl Higher alcohols such as alcohol; polyethylene glycol (eg, macrogol 4000); polyhydric alcohols such as propylene glycol, glycerin, dipropylene glycol, 1,3-butylene glycol, concentrated glycerin; monooleic acid ester, stearic acid glyceride, etc. Fatty acid esters; phosphate buffer and the like. Furthermore, additives such as dissolution aids, inorganic fillers, pH adjusters, humectants, preservatives, thickeners, antioxidants, and cooling agents may be added.

References such as scientific literature, patents, and patent applications cited in this specification are incorporated herein by reference in their entirety to the same extent as if they were specifically described.

The present invention has been described with reference to preferred embodiments for easy understanding. The present invention will now be described based on examples, but it should be understood that the above description and the following examples are provided for illustrative purposes only and are not intended to limit the invention. It is. Accordingly, the scope of the present invention is not limited to the embodiments or examples specifically described in the present specification, but is limited only by the scope of the claims.

(Example 1. Preparation of powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast)
Yeast Saccharomyces cerevisiae K-7 (Sake Yeast Association No. 7) was cultured using a 5 L jar fermenter (feeding medium volume: 3 L) at a culture temperature of 28 ° C., a stirring speed of 500 rpm, a culture time of 36-48 h, and an aeration rate of 0 .5 VVM, medium composition (w / 100 mL): cultured with 5% glucose, 0.75% yeast extract, 2.0% peptone, 0.15% methionine. The culture was centrifuged (8,000 rpm), the supernatant was removed, and the cells were collected. An appropriate amount of the supernatant liquid removed from the recovered cells was added to prepare a cell concentrate.

The concentration of S-adenosylmethionine in the concentrate was measured, and 1.5 mol of phytic acid (TSUNO phytic acid from Tsukino Food Industry Co., Ltd. (Wakayama)) per cell of S-adenosylmethionine contained In addition to the concentrated solution, 1.2 mol of γ-cyclodextrin (γ-100; Pearl Ace Co., Ltd., Tokyo) was added to 1 mol of S-adenosylmethionine contained. This was then frozen overnight at -80 ° C. Lyophilization was performed for 72 hours to prepare a powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast.

(Example 2. Promotion of hyaluronic acid production in chondrocytes)
A human chondrocyte cell line (SW1353) was cultured and maintained at 37 ° C. in Leibovitz's L-15 medium containing 10% fetal bovine serum and antibiotics. The cells were seeded in a 12-well plate at 1.5 × 10 ⁵ cells per well and pre-cultured overnight. Thereafter, the cells were cultured by the following three methods.
(1) The chondrocytes were cultured for 24 hours without adding a substance capable of promoting hyaluronic acid production (data 1 in FIG. 1).
(2) Glucosamine known to have the ability to promote hyaluronic acid production (see JP 2001-2551) was added, and the chondrocytes were cultured for 24 hours (data 2 in FIG. 1). In culture, 0.5 mM glucosamine was added to the medium.
(3) The powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast prepared in Example 1 was added, and the chondrocytes were cultured for 24 hours (data 3 in FIG. 1). In the culture, a powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast was added to the medium so that the S-adenosylmethionine concentration was 0.52 μg / ml.

Subsequently, the culture supernatants of the above three groups were collected, and the amount of hyaluronic acid contained in the culture supernatant was measured using a hyaluronic acid measurement kit sold by Seikagaku Biobusiness Co., Ltd. The amount of hyaluronic acid in each group is shown in FIG. Surprisingly, chondrocytes added with yeast containing S-adenosylmethionine, phytic acid and γ-cyclodextrin produced more hyaluronic acid than chondrocytes added with glucosamine, a so-called positive control (p = 0.003). The results shown in FIG. 1 demonstrated that the powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast promotes hyaluronic acid production by 40% or more in chondrocytes. Glucosamine promoted about 10% hyaluronic acid production in chondrocytes. This indicates that the powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast significantly promotes hyaluronic acid production compared to glucosamine, which was conventionally known to promote hyaluronic acid production. It is shown that.

(Example 3. Promotion of hyaluronic acid production in synovial cells)
A human synovial cell culture cell line (MH7A) was cultured and maintained at 37 ° C. in RPMI-1640 medium containing 10% fetal bovine serum and antibiotics under 5% CO ₂ . The cells were seeded in a 12-well plate at 1.0 × 10 ⁵ cells per well and pre-cultured overnight. Thereafter, the cells were cultured by the following three methods.
(1) The synovial cells were cultured for 24 hours without adding a substance having hyaluronic acid production promoting ability (data 1 in FIG. 2).
(2) Glucosamine known to have hyaluronic acid production promoting ability was added, and the synovial cells were cultured for 24 hours (data 2 in FIG. 2). In culture, 0.5 mM glucosamine was added to the medium.
(3) The powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast prepared in Example 1 was added, and the synoviocytes were cultured for 24 hours (data 3 in FIG. 2). . In the culture, a powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast was added to the medium so that the S-adenosylmethionine concentration was 0.52 μg / ml.

Subsequently, the culture supernatants of the above three groups were collected, and the amount of hyaluronic acid contained in the culture supernatant was measured using a hyaluronic acid measurement kit sold by Seikagaku Biobusiness Co., Ltd. The amount of hyaluronic acid in each group is shown in FIG. Surprisingly, in synovial cells to which S-adenosylmethionine, phytic acid and γ-cyclodextrin-containing yeast were added (data 3 in FIG. 2), synoviocytes to which so-called positive control glucosamine was added (FIG. 2). Higher amounts of hyaluronic acid were produced than data 2). From the results shown in FIG. 2, it was demonstrated that yeast containing S-adenosylmethionine, phytic acid and γ-cyclodextrin promotes hyaluronic acid production by 50% or more in synoviocytes. Glucosamine promoted about 10% hyaluronic acid production in synovial cells. This indicates that the powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast significantly promotes hyaluronic acid production compared to glucosamine, which was conventionally known to promote hyaluronic acid production. It is shown that.

(Example 4. Hyaluronic acid production promoting ability of various components)
From the results of Examples 2 and 3, it is clear that the powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast has a high hyaluronic acid production promoting ability in chondrocytes and synovial cells. became. In this example, it was verified in more detail which of the components contained in the powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast particularly contributes to the promotion of hyaluronic acid production. .

A human chondrocyte cell line (SW1353) was cultured and maintained at 37 ° C. in Leibovitz's L-15 medium containing 10% fetal bovine serum and antibiotics. The cells were seeded in a 12-well plate at 1.5 × 10 ⁵ cells per well and pre-cultured overnight. Thereafter, the cells were cultured by the following method.
(1) The chondrocytes were cultured for 24 hours without adding a substance capable of promoting hyaluronic acid production (data 1 in FIG. 3).
(2) Yeast containing neither S-adenosylmethionine nor phytic acid was added, and the chondrocytes were cultured for 24 hours (data 2 in FIG. 3). This yeast was prepared as follows.

Yeast Saccharomyces cerevisiae K-7 strain (Sake Yeast Association No. 7), 5 L jar fermenter (feeding medium amount: 3 L), culture temperature 28 ° C., stirring speed 500 rpm, culture time 36-48 h, aeration volume 0.5 VVM, Medium composition (w / 100 mL): cultured with 5% glucose, 0.75% yeast extract, and 2.0% peptone. This culture solution was centrifuged (8,000 rpm), and the cells were collected. A supernatant was added to the collected cells to prepare a cell concentrate. The prepared sample was frozen at −80 ° C. overnight. Lyophilization was performed for 72 hours to prepare yeast powder. In the culture, yeast was added to the medium so as to be 14.46 μg / mL.
(3) A powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast was added, and the chondrocytes were cultured for 24 hours (data 3 in FIG. 3). In the culture, a powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast was added so that the S-adenosylmethionine concentration was 0.52 μg / ml.
(4) Only S-adenosyl-L-Methionine Dissolve p-toluenesulfate, CHEmester International Inc. was added, and the chondrocytes were cultured for 24 hours (data 4 in FIG. 3). In the culture, S-adenosylmethionine was added so that the S-adenosylmethionine concentration was 0.52 μg / mL.
(5) The above chondrocytes were cultured for 24 hours with only γ-cyclodextrin added (data 5 in FIG. 3). In the culture, γ-cyclodextrin was added so that the concentration of γ-cyclodextrin was 2.6 μg / mL.
(6) Only the phytic acid was added and the chondrocytes were cultured for 24 hours (data 6 in FIG. 3). In the culture, phytic acid was added so that the phytic acid concentration was 1.3 μg / mL.
(7) Yeast and S-adenosylmethionine were added, and the chondrocytes were cultured for 24 hours (data 7 in FIG. 3). In the culture, yeast powder was added so that the yeast concentration was 14.46 μg / mL, and S-adenosylmethionine was added so that the S-adenosylmethionine concentration was 0.52 μg / mL.
(8) Phytic acid and S-adenosylmethionine were added, and the chondrocytes were cultured for 24 hours (data 8 in FIG. 3). In the culture, phytic acid was added so that the phytic acid concentration was 1.3 μg / mL, and S-adenosylmethionine was added so that the S-adenosylmethionine concentration was 0.52 μg / mL.
(9) γ-cyclodextrin and S-adenosylmethionine were added, and the chondrocytes were cultured for 24 hours (data 9 in FIG. 3). In the culture, γ-cyclodextrin was added so that the γ-cyclodextrin concentration was 2.6 μg / mL, and S-adenosylmethionine was added so that the S-adenosylmethionine concentration was 0.52 μg / mL. .

As shown in FIG. 3, the addition of only yeast, S-adenosylmethionine, γ-cyclodextrin and phytic acid components to the medium did not affect the hyaluronic acid production ability of chondrocytes ( (See

data

2, 4, 5 and 6 in FIG. 3) On the other hand, when a powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast (data 3 in FIG. 3) is added When phytic acid and S-adenosylmethionine (data 8 in FIG. 3) were added, the amount of hyaluronic acid produced by chondrocytes was significantly increased relative to the control (p = 0 for data 3). 0.027; for data 8, p = 0.002). From this result, it was demonstrated that the combination of S-adenosylmethionine and phytic acid has a hyaluronic acid production promoting effect.

(Example 5. Promotion of hyaluronic acid production in skin fibroblasts)
Normal human dermal fibroblast cell line was seeded in 96-well microplate using Dulbecco's modified MEM (DMEM) containing 0.5% calf serum (FBS) at a cell density of 2.0 × 10 ⁴ cells / well did. 24 hours after sowing, the cells were cultured for 24 hours in a DMEM medium containing 0.5% FBS containing test samples having the following concentrations (n = 5). After culturing for 24 hours, the amount of hyaluronic acid in the culture supernatant was analyzed by ELISA. For analysis by ELISA method, a commercially available measurement kit was used and quantified according to a conventional method. The ELISA method used in the measurement of hyaluronic acid is a competitive method, and the obtained colorimetric change is inversely proportional to the amount of hyaluronic acid contained in the sample. According to the kit, the colorimetric change is digitized using an enzyme-labeled antibody and a colorimetric detection reagent for the sample. This value is used for quantification by a calibration curve obtained from a standard product.
The results are shown in FIG.
(1) No additional substances are added (see data 1 in FIG. 4).
(2) 0.50 μg / mL S-adenosylmethionine and 1.25 μg / mL phytic acid (see data 2 in FIG. 4).
(3) 1.00 μg / mL S-adenosylmethionine and 2.50 μg / mL phytic acid (see data 3 in FIG. 4).
(4) 10.00 μg / mL S-adenosylmethionine and 25.00 μg / mL phytic acid (see data 4 in FIG. 4).
(5) 0.005 w / w% of a powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast prepared in Example 1 (into an amount of S-adenosylmethionine of 0.50 μg / mL) (Refer to data 5 in FIG. 4).
(6) A powder composition containing 0.010 w / w% of S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast prepared in Example 1 (into an amount of S-adenosylmethionine of 1.00 μg / mL) Equivalent) (see data 6 in FIG. 4).
(7) 0.100 w / w% of a powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin and yeast prepared in Example 1 (into an amount of S-adenosylmethionine of 10.00 μg / mL) (Refer to data 7 in FIG. 4).
(8) 0.005 w / w% yeast containing phytic acid (1.25 μg / mL) and γ-cyclodextrin (2.00 μg / mL) (see data 8 in FIG. 4).
(9) 0.010 w / w% yeast containing phytic acid (2.50 μg / mL) and γ-cyclodextrin (4.00 μg / mL) (see data 9 in FIG. 4).
(10) 0.100 w / w% phytic acid (25.00 μg / mL) and γ-cyclodextrin (40.00 μg / mL) -containing yeast (see data 10 in FIG. 4).

As is clear from the results shown in FIG. 4, the S-adenosylmethionine and phytic acid addition group (data 2 to 4 in FIG. 4) and the S-adenosylmethionine, phytic acid, γ-cyclohexane prepared in Example 1 The amount of hyaluronic acid produced in the powder composition-added group containing dextrin and yeast (data 6 to 7 in FIG. 4) was determined from the untreated human dermal fibroblast cell line culture (data 1 in FIG. 4) or phytic acid and The amount of hyaluronic acid produced in the γ-cyclodextrin-containing yeast addition group (data 8 to 10 in FIG. 4) was significantly increased.
For chondrocytes and synoviocytes, yeast containing S-adenosylmethionine, phytic acid and γ-cyclodextrin in an amount corresponding to 0.52 μg / mL of S-adenosylmethionine was added. In some cases, hyaluronic acid production was promoted, but in human dermal fibroblasts, an amount (0.50 μg / mL) of S-adenosylmethionine, phytic acid, approximately the same amount of S-adenosylmethionine, When a powder composition containing γ-cyclodextrin and yeast was added (see data 5 in FIG. 4), no significant effect was observed, with higher concentrations (1.00 μg / mL and 10.00 μg / mL). Hyaluronic acid production enhancement was observed when mL) of S-adenosylmethionine was added (see

data

6 and 7 in FIG. 4). From these results, it was suggested that the appropriate amount of the powder composition containing S-adenosylmethionine, phytic acid, γ-cyclodextrin, and yeast to promote hyaluronic acid production varies depending on the target cells.

As mentioned above, although this invention has been illustrated using preferable embodiment of this invention, this invention should not be limited and limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range based on the description of the present invention and the common general technical knowledge from the description of specific preferred embodiments of the present invention.

Claims

A composition for promoting hyaluronic acid production, comprising S-adenosylmethionine and phytic acid.
The composition of claim 1 further comprising a cyclodextrin.
The composition according to claim 2, wherein the cyclodextrin is γ-cyclodextrin.
Furthermore, the composition of Claim 3 containing yeast.
The composition according to claim 4 for the treatment of arthropathy.
The composition according to claim 4 for improving beauty.
The composition according to claim 6, which is a cosmetic.
A method for producing the hyaluronic acid production promoting composition according to claim 1,
A production method comprising a step of culturing yeast to produce S-adenosylmethionine, and a step of adding phytic acid to a culture solution of the yeast.
The production method according to claim 8, further comprising a step of adding cyclodextrin to the culture solution.
The production method according to claim 9, wherein the cyclodextrin is γ-cyclodextrin.
The manufacturing method of Claim 10 which adds the said cyclodextrin to the said culture solution after the addition of the said phytic acid.
The manufacturing method of Claim 11 whose said culture solution is a microbial cell concentrate.
The production method according to claim 8, wherein the pH of the culture solution after addition of the phytic acid is 3 or less.
The production method according to claim 8, further comprising a step of drying the culture solution.
The manufacturing method according to claim 10, wherein the composition is a composition for treatment of arthropathy, a cosmetic improvement composition, or a cosmetic.