JP7197402B2 - anti aging agent - Google Patents

Description

The present invention relates to anti-aging agents.

The skin has a three-layer structure consisting of the epidermis, dermis, and subcutaneous tissue. In the dermis, type I collagen aggregates to form bundles, which play a role as dermal struts, and components such as elastin and hyaluronic acid are present around them. When these components decrease or decompose due to aging, ultraviolet irradiation, or the like, the skin loses its firmness and luster, and wrinkles are likely to form.

Various anti-aging agents have been investigated in order to suppress such skin aging. Patent Literature 1 discloses an anti-aging agent characterized by containing an extract from Astragalus membranaceus and/or oil tea as an active ingredient. Patent Document 2 discloses an anti-aging agent containing an extract of one or more plants selected from plants belonging to the genus Maki of the family Maki family. Patent Document 3 discloses an anti-aging agent characterized by containing an extract of Thymus vulgaris as an active ingredient. Patent Document 4 discloses a collagen production promoter, a collagenase inhibitor, and an elastase inhibitor characterized by containing an extract from carambola leaves as an active ingredient.

JP-A-2010-83786 JP 2010-70501 A JP-A-11-79971 Japanese Patent Application Laid-Open No. 2002-226323

An object of the present invention is to provide a novel anti-aging agent.

The present inventors found that the decomposed extract of bagasse has an anti-aging effect by in vitro tests.

One aspect of the present invention provides an anti-aging agent containing a bagasse decomposition extract as an active ingredient. The anti-aging agent of the present invention has an excellent anti-aging effect by containing the decomposition extract of bagasse as an active ingredient.

The decomposition extract of bagasse may be a decomposition-treated liquid obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment and explosion treatment.

The bagasse decomposition extract may be a fraction obtained by passing a decomposition-treated liquid through a column filled with a solid carrier. The fixed carrier is preferably a synthetic adsorbent or an ion exchange resin.

When the immobilizing carrier is a synthetic adsorbent, the bagasse decomposition extract extracts the components adsorbed by the synthetic adsorbent with at least one solvent selected from the group consisting of water, methanol, ethanol, and mixtures thereof. It may be a fraction obtained by allowing

The synthetic adsorbent is preferably an aromatic resin, an acrylic methacrylic resin, or an acrylonitrile aliphatic resin.

The decomposition extract of bagasse is obtained by passing the decomposition treated liquid through a column filled with a synthetic adsorbent as a fixed carrier, and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water. In this case, the synthetic adsorbent is an unsubstituted aromatic resin, the column temperature is 20 to 60 ° C., and the volume ratio of ethanol and water in the mixed solvent (ethanol /water) may be from 50/50 to 60/40.

It can also be said that the present invention provides, as another aspect, an extracellular matrix degrading enzyme inhibitor containing a bagasse decomposition extract as an active ingredient. It can also be said that the present invention provides a fibroblast activator as still another aspect.

ADVANTAGE OF THE INVENTION According to this invention, a novel anti-aging agent can be provided.

Embodiments of the present invention will be described below. However, the present invention is not limited to the following embodiments.

The anti-aging agent of the present invention has an anti-aging action. The anti-aging effect may be the effect of suppressing skin aging, and more specifically, the effect of suppressing and/or improving skin functional deterioration due to aging, ultraviolet irradiation, or the like. The anti-aging action may be an action of suppressing and/or improving skin wrinkles, sagging, hardening, and the like.

Components such as type I collagen, elastin, and hyaluronic acid contained in the dermis are also called extracellular matrix components. Extracellular matrix components are produced from fibroblasts. One cause of skin aging is the degradation or loss of extracellular matrix components.

Degradation of extracellular matrix components occurs by extracellular matrix degrading enzymes. For example, type I collagen is degraded by matrix metalloprotease (MMP-1), which is a kind of extracellular matrix degrading enzyme. The activity of MMP-1 is enhanced by increasing the amount of protein when irradiated with ultraviolet rays. The production and increased activity of MMP-1 can result in collagen loss, degeneration, loss of skin elasticity, and the formation of wrinkles or sagging skin. On the other hand, elastin is degraded by elastase, which is a type of extracellular matrix degrading enzyme. Elastin plays a role like a spring that connects collagen fibers, but the degradation of elastin by elastase can also cause the skin to lose its elasticity and cause the formation of wrinkles or sagging of the skin.

The anti-aging agent of the present invention has an action of inhibiting extracellular matrix-degrading enzymes (an action of suppressing production of extracellular matrix-degrading enzymes, an action of reducing activity of extracellular matrix-degrading enzymes). It has an action of inhibiting MMP-1, which degrades type I collagen, and/or an action of inhibiting elastase, which degrades elastin. This suppresses skin aging. That is, the anti-aging agent of the present invention can be said to be based on the inhibitory action of extracellular matrix-degrading enzymes, and more specifically, it is based on the inhibitory action of MMP-1 or elastase. You can also say. The present invention can also be said to provide extracellular matrix degrading enzyme inhibitors, and more specifically, to provide MMP-1 inhibitors or elastase inhibitors.

More specifically, the action of inhibiting MMP-1 may be an action of inhibiting production of MMP-1, or an action of inhibiting activity of MMP-1. More specifically, the action of inhibiting elastase may be the action of inhibiting the production of elastase, or the action of inhibiting the activity of elastase. That is, the anti-aging agent of the present invention may be based on at least one of MMP-1 production inhibitory action, MMP-1 activity inhibitory action, elastase production inhibitory action, and elastase activity inhibitory action. . The anti-aging agent of the present invention may be based on MMP-1 production inhibitory action and/or elastase activity inhibitory action. The present invention can also be said to provide an MMP-1 production inhibitor, an MMP-1 activity inhibitor, an elastase production inhibitor, or an elastase activity inhibitor. The present invention can also be said to provide MMP-1 production inhibitors or elastase activity inhibitors.

On the other hand, the amount of extracellular matrix components produced decreases due to deterioration of fibroblasts due to aging, ultraviolet irradiation, and the like. By activating fibroblasts, it is possible to suppress the decrease in the production of extracellular matrix components. Since the anti-aging agent of the present invention also has the effect of activating fibroblasts, skin aging is further suppressed. That is, it can be said that the anti-aging agent of the present invention is based on fibroblast activating action. The present invention can also be said to provide a fibroblast activator.

An anti-aging agent according to one embodiment contains a bagasse decomposition extract as an active ingredient. The bagasse decomposition extract preferably contains at least one selected from the group consisting of p-coumaric acid, ferulic acid, caffeic acid, phenylpropanoids such as vanillin, and lignin and its decomposition products.

"Bagasse" typically refers to bagasse discharged during the sugar manufacturing process in the raw material sugar manufacturing process. The bagasse discharged in the sugar manufacturing process at the raw sugar factory includes not only the final bagasse that has left the final press, but also the shredded sugar cane that has been bitten into the subsequent presses including the first press. A suitable bagasse is the bagasse that is discharged after pressing the juice by the pressing process in the raw sugar mill. The bagasse varies in water content, sugar content, and composition ratio thereof depending on the type of sugar cane, harvest time, etc., but any of these bagasse can be used in the present invention. Furthermore, in the present embodiment, the bagasse used as the raw material is, for example, the bagasse remaining after pressing the cane discharged at the brown sugar manufacturing plant, similarly to the raw material sugar factory, or the sugar liquid is squeezed from the sugar cane by small-scale laboratory-level implementation. Later bagasse can also be used.

The bagasse decomposition extract may, in one embodiment, be a decomposition treated liquid of bagasse (and/or its processed product). The decomposition treatment liquid can be obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment and explosion treatment. Degradation treatment of bagasse herein requires that some or all of the chemical structures of lignin, cellulose, and/or hemicellulose be destroyed. The decomposition treatment is preferably an alkali treatment or a hydrothermal treatment from the viewpoint of easily obtaining a decomposition extract of bagasse.

The alkali treatment may be a treatment of contacting the bagasse with an alkaline solution. Examples of the method of bringing the alkaline solution into contact include a method of sprinkling the bagasse with the alkaline solution, a method of immersing the bagasse in the alkaline solution, and the like. In the method of immersing the bagasse in the alkaline solution, the mixture of the bagasse and the alkaline solution may be immersed while stirring.

Alkaline solutions include sodium hydroxide aqueous solution, potassium hydroxide aqueous solution, ammonia aqueous solution and the like. Alkaline solutions may be used alone or in combination of two or more of these solutions. The alkaline solution is preferably an aqueous sodium hydroxide solution because it is inexpensive and can be easily used in the food manufacturing process.

The temperature (liquid temperature) of the alkaline solution is preferably 40° C. or higher, more preferably 100° C. or higher, and still more preferably 130° C. or higher, from the viewpoint of shortening the treatment time of the decomposition treatment. The temperature of the alkaline solution is preferably 250° C. or lower, more preferably 200° C. or lower, and still more preferably 150° C. or lower from the viewpoint of preventing the polysaccharide from remaining in the decomposition treatment liquid.

The alkali treatment may be performed under normal pressure or under pressure. When pressurized, the pressure may be 0.1 MPa or more, or 0.2 MPa or more, and may be 4.0 MPa or less, 1.6 MPa or less, or 0.5 MPa or less.

The hydrothermal treatment may be a process of contacting bagasse with hot water or steam under high pressure. More specifically, the hydrothermal treatment may be, for example, a method in which water is added so that the bagasse has a solid concentration of 0.1 to 50%, and decomposition treatment is performed under high temperature and high pressure conditions. The temperature of water or steam is preferably 130 to 250° C., and the applied pressure is preferably 0.1 to 0.5 MPa higher than the saturated steam pressure of water at each temperature.

The acid treatment may be a treatment of contacting the bagasse with an acidic solution. Dilute sulfuric acid etc. are mentioned as an acidic solution. The method of bringing the acid solution into contact with the bagasse, the temperature of the acid solution in the acid treatment, and the pressure conditions in the acid treatment may be the same as those in the alkali treatment described above.

The subcritical water treatment may be a treatment of contacting bagasse with subcritical water. The method of contacting bagasse with subcritical water may be the same as the method in the alkali treatment described above. The conditions for the subcritical water treatment are not particularly limited, but it is preferable to set the temperature of the subcritical water to 160 to 240° C. and the treatment time to 1 to 90 minutes.

In the blasting treatment, the insoluble xylan contained in the bagasse is decomposed to some extent by hydrothermal treatment, and then the bagasse is pulverized by instantly releasing it to atmospheric pressure by opening a valve provided in the pressure-resistant reaction vessel at once. It may be processing.

After the decomposition treatment described above, the decomposition treatment liquid may be subjected to a treatment for separating the solid content and the liquid content. In this case, the liquid component obtained after the separation can be used as the decomposition treatment liquid. The method of separating solids and liquids may be separation by strainer, filtration, centrifugation, decantation, and the like.

In the decomposition treatment liquid, high-molecular components such as polysaccharides may be removed by membrane separation. In this case, the liquid component after membrane separation can be used as the decomposition treatment liquid. The separation membrane is not particularly limited as long as it is an ultrafiltration membrane (UF membrane). The molecular weight cutoff of the ultrafiltration membrane is preferably 2,500-50,000, more preferably 2,500-5,000.

Ultrafiltration membrane materials include polyimide, polyethersulfone (PES), polysulfone (PS), polyacrylonitrile (PAN), polyvinylidene fluoride (PVDF), regenerated cellulose, cellulose, cellulose ester, sulfonated polysulfone, sulfonated Polyethersulfone, polyolefin, polyvinyl alcohol, polymethyl methacrylate, polytetrafluoroethylene, and the like can be used.

The filtration method of the ultrafiltration membrane may be dead-end filtration or cross-flow filtration, but cross-flow filtration is preferable from the viewpoint of suppressing membrane fouling.

As the form of the ultrafiltration membrane, an appropriate form such as a flat membrane type, a spiral type, a tubular type, or a hollow fiber type can be used. More specifically, GE Power & Water's GE series, GH series, GK series, DESAL's G-5 type, G-10 type, G-20 type, G-50 type, PW type, HWSUF type, KOCH's HFM-180, HFM-183, HFM-251, HFM-300, HFK-131, HFK-328, MPT-U20, MPS-U20P, MPS-U20S, Synder SPE1, SPE3, SPE5, SPE10, SPE30, SPV5 , SPV50, SOW30, Microza (registered trademark) UF series manufactured by Asahi Kasei Corporation having a molecular weight cut off of 3,000 to 10,000, and NTR7410 and NTR7450 manufactured by Nitto Denko Corporation.

In another embodiment, the bagasse decomposition extract may be a fraction obtained by passing the decomposition-treated liquid described above through a column filled with a solid carrier. By passing the decomposed liquid through the column, the component having anti-aging action (active ingredient) in the decomposed liquid is adsorbed on the fixed carrier, and most of the saccharides and inorganic salts flow out as they are.

The decomposition treatment liquid described above can be passed through the column directly or after being adjusted to an arbitrary concentration with water. The pH of the decomposition treatment solution may be adjusted before passing through the column. From the viewpoint of improving the adsorption rate, the decomposition treatment liquid is preferably adjusted to pH 6 or less. The pH of the decomposition treatment liquid may be more than 4.5 and 6 or less.

The fixed carrier is preferably either a synthetic adsorbent or an ion exchange resin.

The synthetic adsorbent is preferably a synthetic porous adsorbent. As the synthetic adsorbent (synthetic porous adsorbent), an organic resin is preferably used. The organic resin is preferably an aromatic resin, an acrylic methacrylic resin, or an acrylonitrile aliphatic resin.

Examples of aromatic resins include styrene-divinylbenzene resins. Examples of aromatic resins include porous resins such as aromatic resins having hydrophobic substituents, non-substituted aromatic resins, and non-substituted aromatic resins specially treated. Of these, unsubstituted aromatic resins or unsubstituted aromatic resins specially treated are preferred.

Commercially available synthetic adsorbents include Diaion (trademark) HP-10, HP-20, HP-21, HP-30, HP-40, and HP-50 (these are non-substituted aromatic resins , All are trade names, manufactured by Mitsubishi Chemical Corporation); family resins, both trade names, manufactured by Mitsubishi Chemical Corporation); SP-900 (aromatic resin, trade name, manufactured by Mitsubishi Chemical Corporation); Amberlite (trademark) XAD-2, XAD-4, XAD- 16, XAD-2000 (above, aromatic resins, all trade names, manufactured by Organo Co., Ltd.); Diaion (trademark) SP-205, SP-206, SP-207 (above, aromatics having hydrophobic substituents family resins, both trade names, manufactured by Mitsubishi Chemical Corporation); HP-2MG, EX-0021 (above, aromatic resins having hydrophobic substituents, trade names, manufactured by Mitsubishi Chemical Corporation); Amber Light (trademark) XAD-7, XAD-8 (above, acrylic acid ester resin, both trade names, manufactured by Organo Co., Ltd.); Diaion (trademark) HP1MG, HP2MG (above, acrylic acid methacrylic resin, both trade names , Mitsubishi Chemical Co., Ltd.); Sephadex (trademark) LH20, LH60 (derivatives of crosslinked dextran, both trade names, manufactured by Pharmacia Biotech Co., Ltd.), and the like. Among them, an unsubstituted aromatic resin (eg, HP-20) or an unsubstituted aromatic resin (eg, SP-850) which has undergone a special treatment is preferable.

The amount of the synthetic adsorbent to be packed in the column can be appropriately determined depending on the size of the column, the type of the synthetic adsorbent, and the like.

When a synthetic adsorbent is used as the immobilizing carrier, the flow rate of the decomposition treatment solution can be appropriately changed depending on the size of the column, the type of elution solvent, the type of synthetic adsorbent, etc., but is preferable. is SV=1 to 30 h− ¹ . Note that SV (Space Velocity) is a unit indicating how many times the resin volume of liquid is passed per hour.

The adsorbed component (active component) adsorbed by the synthetic adsorbent can be eluted with a solvent (elution solvent). From the viewpoint of recovering the adsorbed components more efficiently, it is preferable to wash away the saccharides and inorganic salts remaining in the column with water before eluting the adsorbed components. In this case, the eluted component can be a bagasse decomposition extract.

When a synthetic adsorbent is used as the immobilizing carrier, the elution solvent may be at least one selected from the group consisting of water, methanol, ethanol and mixtures thereof. The elution solvent is preferably a mixed solvent of alcohol and water, more preferably a mixed solvent of ethanol and water, and from the viewpoint that the adsorbed component can be more efficiently eluted at room temperature, the volume ratio is 50/50 to 60/40 /water), a mixed solvent of ethanol and water is more preferred.

When a synthetic adsorbent is used as the immobilizing carrier, the temperature of the column (column temperature) during elution may be room temperature. The mixing ratio can be reduced, and the adsorbed components can be eluted more efficiently. The temperature is preferably 20-60°C, more preferably 40-60°C. The inside of the column may be under normal pressure conditions or under pressurized conditions.

When a synthetic adsorbent is used as the immobilizing carrier, the elution rate can be appropriately set depending on the size of the column, the type of elution solvent, the type of synthetic adsorbent, etc., but preferably SV=0.1 to 10 hours ^-1 .

Ion exchange resins are classified into gel-type resins and porous resins such as porous, microporous, and highly porous resins based on the form of the resin, but there is no particular limitation. The ion exchange resin is preferably an anion exchange resin. As the anion exchange resin, a strongly basic anion exchange resin or a weakly basic anion exchange resin may be used. When an alkaline treatment liquid is used as a raw material, a strongly basic anion exchange resin is preferably used.

Commercially available strongly basic anion exchange resins include Diaion (trademark) PA306, PA308, PA312, PA316, PA318L, HPA25, SA10A, SA12A, SA11A, SA20A, UBA120 (manufactured by Mitsubishi Chemical Corporation), Amberlite (Trademarks) IRA400J, IRA402Bl, IRA404J, IRA900J, IRA904, IRA458RF, IRA958, IRA410J, IRA411, IRA910CT (manufactured by Organo Co., Ltd.), Dowex (trademark) Marathon A, Marathon MSA, MONOSPHERE550A, Marathon A2 (all Dow Chemical Nippon Co., Ltd.) and the like.

Commercially available weakly basic anion exchange resins include Diaion (trademark) WA10, WA20, WA21J, WA30 (manufactured by Mitsubishi Chemical Corporation), Amberlite (trademark) IRA478RF, IRA67, IRA96SB, IRA98, and XE583 (manufactured by Mitsubishi Chemical Corporation). , Organo Co., Ltd.), Dowex (trademark) Marathon WBA, 66, MONOSPHERE66, MONOSPHERE77 (manufactured by Dow Chemical Japan Co., Ltd.), and the like.

The amount of ion-exchange resin packed in the column can be appropriately determined depending on the size of the column, the type of ion-exchange resin, and the like. ~500 times wet volume is more preferred.

The conditions for passing the liquid can be appropriately set according to the type of the pretreatment liquid, the type of the ion exchange resin, and the like. Preferably, the flow rate is SV=0.3 to 30 hours ^-1 , the flow rate is 100 to 300% of the ion exchange resin, and the column temperature is 40 to 90.degree. The inside of the column may be in a normal pressure or a pressurized state.

When an ion-exchange resin is used as the immobilizing carrier, the bagasse decomposition extract is passed through a column filled with the ion-exchange resin and eluted with an eluent such as a salt, an acid, an alcohol, or a mixed aqueous solution thereof. It may be a fraction. The eluent may be degassed.

The decomposition extract of bagasse, in one embodiment, may be a concentrate obtained by concentrating the above-described decomposition treated liquid or fraction. The concentration method may be a known method, for example, solvent distillation under reduced pressure, lyophilization, or the like. When concentrating, the decomposition-treated liquid or fraction can be concentrated 15 to 30 times, and the concentrated component can be used as a decomposition extract of bagasse.

A decomposition extract of bagasse can be obtained, for example, as follows. A 1% by mass sodium hydroxide aqueous solution is added to the bagasse so that the solid concentration is 0.1 to 50%, and the mixture is boiled at 100° C. to obtain a decomposition treatment liquid (alkaline treatment liquid). The decomposition-treated liquid is subjected to ultrafiltration with a UF membrane having a molecular weight cutoff of 2500 to 5000, and the obtained filtrate is adjusted to acidity, and then a column filled with an unsubstituted aromatic resin is added to the column. Pass the liquid at a temperature of 20 to 60°C. Thereafter, the components adsorbed on the column are eluted with a mixed solvent (elution solvent) of ethanol and water having a volume ratio of 50/50 to 60/40 (ethanol/water) at a column temperature of 20 to 60° C., and ethanol A fraction eluted within 45 times the wet volume of the aromatic resin from the start of elution with a mixed solvent of water and water is collected. Collected fractions (fractions containing components having anti-aging action) are collected and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a bagasse decomposition extract. can. The bagasse decomposition extract thus obtained can be stored as a concentrated liquid or powder extract having a solid content of 30% by mass or more. Preservation of the extract is preferably carried out by refrigeration when the extract is liquid.

As another example, the decomposition extract of bagasse can also be obtained as follows. That is, water is added to bagasse so that the solid concentration is 0.1 to 50%, hydrothermal treatment is performed with water at 130 to 250 ° C. under a pressure of 0.2 to 4.0 MPa, and solid-liquid by filtration. A decomposition treatment liquid (hydrothermal treatment liquid) is obtained by separation. The resulting hydrothermal treatment solution was passed through a column filled with an aromatic resin that had been specially treated to be unsubstituted, at a temperature of 20 to 60 ° C., and then the components adsorbed in the column were measured at the column temperature. At 20 to 60 ° C., eluted with a mixed solvent (elution solvent) of ethanol and water at a volume ratio of 50/50 to 60/40 (ethanol/water), and collected from the start of elution with a mixed solvent of ethanol and water. Collect the fraction in which the amount of eluate obtained is within 5 times the wet volume of the aromatic resin. Collected fractions (fractions containing components having anti-aging action) are collected and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a bagasse decomposition extract. can. The bagasse decomposition extract thus obtained can be stored as a concentrated liquid or powder extract having a solid content of 30% by mass or more. Preservation of the extract is preferably carried out by refrigeration when the extract is liquid.

The bagasse decomposition extract in each of the above-described embodiments may be liquid or powder. The powdery bagasse decomposition extract is produced, for example, using a liquid bagasse decomposition extract by a spray drying method, a freeze-drying method, a fluid bed granulation method, or a pulverization method using an excipient. be able to.

Anti-aging agents can be used as cosmetics, food compositions, pharmaceuticals, or quasi-drugs. The food composition may be provided in the form of, for example, health food, food for specified health uses, functional food, food with nutrient function claims, supplement, and the like.

The anti-aging agent may consist only of the decomposition extract of bagasse, which is an active ingredient, or may further contain materials that can be used in cosmetics, food compositions, quasi-drugs, or pharmaceuticals. Materials that can be used in cosmetics, food compositions, quasi-drugs, or pharmaceuticals are not particularly limited, but examples include amino acids, proteins, carbohydrates, fats and oils, sweeteners, minerals, vitamins, flavors, and excipients. agents, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, suspending agents and the like.

Proteins include, for example, milk casein, whey, soybean protein, wheat protein, egg white and the like. Carbohydrates include, for example, corn starch, cellulose, pregelatinized starch, wheat starch, rice starch, potato starch and the like. Fats and oils include, for example, salad oil, corn oil, soybean oil, safflower oil, olive oil, palm oil and the like. Sweeteners include, for example, sugars such as glucose, sucrose, fructose, high-fructose corn syrup, high-fructose corn syrup, sugar alcohols such as xylitol, erythritol, and maltitol, and artificial sweeteners such as sucralose, aspartame, saccharin, and acesulfame K. sweeteners, stevia sweeteners, and the like. Minerals include, for example, calcium, potassium, phosphorus, sodium, manganese, iron, zinc, magnesium, and salts thereof. Examples of vitamins include vitamin E, vitamin C, vitamin A, vitamin D, B vitamins, biotin, niacin and the like. Excipients include, for example, dextrin, starch, lactose, crystalline cellulose and the like. Examples of binders include polyvinyl alcohol, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone and the like. Lubricants include, for example, magnesium stearate, calcium stearate, talc and the like. Examples of disintegrants include crystalline cellulose, agar, gelatin, calcium carbonate, sodium hydrogencarbonate, dextrin and the like. Examples of emulsifiers or surfactants include sucrose fatty acid esters, citric acid, lactic acid, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, and lecithin. Bases include, for example, cetostearyl alcohol, lanolin, polyethylene glycol and the like. Examples of solubilizing agents include polyethylene glycol, propylene glycol, sodium carbonate, sodium citrate and the like. Suspending agents include, for example, glyceryl monostearate, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxymethylcellulose, sodium alginate and the like. These may be used alone or in combination of two or more.

When the anti-aging agent is blended with other materials, the content of the bagasse decomposition extract, which is an active ingredient, may be appropriately set according to the form of the anti-aging agent described later, the purpose of use, etc., but the anti-aging effect From the viewpoint of more effectively exhibiting the solid content, it is preferably 0.5% by mass or more, more preferably 1% by mass or more, still more preferably 3% by mass or more, and preferably 50% by mass. % by mass or less, more preferably 40% by mass or less, and even more preferably 30% by mass or less.

The shape of the anti-aging agent is not limited, and may be solid (powder, granules, etc.), liquid (solution, suspension, etc.), paste, etc., powders, pills, granules, tablets, Any dosage form such as a capsule, troche, liquid, or suspension may be used.

When the anti-aging agent is used as a cosmetic, the cosmetic includes basic cosmetics such as lotion, milky lotion, lotion, cream, beauty essence, oil, mask, and lip balm, hair styling agents such as hair tonic and hair liquid, and hair growth and nourishment. Hair cosmetics such as hair materials, makeup cosmetics such as foundations, lipsticks, blushers, eye shadows, eyeliners, mascara, and eyebrow liners.

The anti-aging agent may be administered orally or may be administered parenterally.

When the anti-aging agent is orally administered, the dose is preferably, for example, 50 μg/kg (body weight) or more, preferably 100 μg/kg (body weight), of the bagasse decomposition extract per administration. It is more preferable to administer the drug so that it reaches 150 μg/kg (body weight) or more, and it is even more preferable to administer it so that it reaches 150 μg/kg (body weight) or more. In addition, the bagasse decomposition extract is preferably administered at a daily dose of 150 µg/kg (body weight) or more, more preferably 300 µg/kg (body weight) or more, and more preferably 450 µg/kg. (body weight) or more is more preferably administered. In addition, the bagasse decomposition extract is preferably administered at a dose of 1000 mg/kg (body weight) or less, more preferably 800 mg/kg (body weight) or less, and 600 mg/kg (body weight) or less. It is more preferable to administer so as to give kg (body weight) or less. In addition, the content of the bagasse decomposition extract is preferably 3000 mg/kg (body weight) or less per day, more preferably 2000 mg/kg (body weight) or less, and more preferably 1000 mg/kg. It is more preferable to administer so that (body weight) is as follows. Within this range, the anti-aging agent can act on the dermis at a sufficient concentration, and the anti-aging action can be better expressed.

When the anti-aging agent is applied to the skin as parenteral administration, the amount of application to the skin is preferably, for example, 5 μg/cm ² or more of the bagasse decomposition extract per application. , 10 μg/cm ² or more, more preferably 30 μg/cm ² or more. In addition, the content of the bagasse decomposition extract is preferably 10 μg/cm ² or more per day, more preferably 20 μg/cm ² or more, and more preferably 60 μg/cm ² or more. More preferably, it is applied as follows. In addition, the bagasse decomposition extract is preferably applied so as to be 500 μg/cm ² or less per application, more preferably 400 μg/cm ² or less, and 300 μg/cm ² or less. More preferably, it is applied so that In addition, the content of the bagasse decomposition extract per day is preferably 1000 μg/cm ² or less, more preferably 800 μg/cm ² or less, and more preferably 600 μg/cm ² or less. More preferably, it is applied as follows. Within this range, the anti-aging agent can act on the dermis at a sufficient concentration, and the anti-aging action can be better expressed.

Anti-aging agents can also be used as feeds and feed additives. Feeds include companion animal feeds such as dog food and cat food, livestock feeds, poultry feeds, farmed fish and shellfish feeds, and the like. "Food" includes anything orally ingested by an animal for nutritional purposes. More specifically, when classified in terms of nutrient content, it includes all of rough feed, concentrated feed, mineral feed, and special feed, and in terms of official standards, it includes all of compound feed, mixed feed, and single feed. encompasses In addition, when classified from the aspect of feeding method, it includes all feeds that are directly fed, feeds that are mixed with other feeds, and feeds that are added to drinking water to supplement nutrients.

Specific aspects of the extracellular matrix degrading enzyme inhibitor or fibroblast activator according to one embodiment may be the same as those of the anti-aging agent described above. That is, the extracellular matrix degrading enzyme inhibitor or fibroblast activator according to one embodiment is such that in the description of the anti-aging agent described above, "anti-aging agent" is replaced with "extracellular matrix degrading enzyme inhibitor" or "fibroblast activator". It may be read as "cell activator".

EXAMPLES The present invention will be described below with reference to Examples, but the present invention is not limited to these Examples. The decomposition extract of bagasse may be hereinafter simply referred to as "extract".

<Production of bagasse decomposition extract>
[Production Example 1]
15 kg of sugarcane pomace bagasse (water content: 50% by mass) and 100 L of 0.5% (w/w) sodium hydroxide aqueous solution were mixed and subjected to alkali treatment at 150°C. The mixed liquid after the alkali treatment was separated into a solid content and a liquid content to obtain about 100 L of the liquid content. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500 to obtain 80 L of filtrate. Synthetic adsorbent (HP-20, manufactured by Mitsubishi Chemical Co., Ltd.) 1 liter is filled in a resin tower (inner diameter 80 mm, height 400 mm), and the above filtrate is added to it after adjusting the pH to 6, and the flow rate is 10 liters. / hour (SV = 10.0 (hour ^{- 1} )).

Subsequently, 5 liters of purified water was passed through the resin tower at a flow rate of 10 liters/hour (SV=10.0 (time ^-1 )) to wash the resin. Next, 2 liters of a 60% aqueous ethanol solution (ethanol/water = 60/40 (volume/volume)) was passed through the resin column at a flow rate of 2 liters/hour (SV = 2.0 (time ^{- 1} )) as an elution solvent. liquid. Subsequently, 2 liters of purified water was passed through the resin column at a flow rate of 2 liters/hour (SV=2.0 (hour ⁻¹ )) to elute the components adsorbed by the synthetic adsorbent. The fraction eluted from the resin column was concentrated under reduced pressure to about 10 times the concentration using a rotary evaporator, and freeze-dried overnight to obtain 20 g of brown powder as a bagasse decomposition extract. This was designated as extract A.

[Production Example 2]
30 kg of bagasse (water content: 50% by mass), which is sugarcane pomace, was subjected to hydrothermal treatment with 100 L of hot water at 200° C. and 1.8 MPa. The mixed liquid after the pretreatment was separated into a solid content and a liquid content to obtain about 88 L of the liquid content. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500 to obtain 70 L of filtrate. 1 L of synthetic adsorbent (manufactured by Mitsubishi Chemical Corporation, SP-850) was filled in a resin tower (inner diameter 80 mm, height 400 mm), and 25 L of the above filtrate was added thereto at a flow rate of 20 L/hour (SV=20. 0 (time ^-1 )).

Subsequently, 3.3 L of purified water was passed through the resin tower at a flow rate of 20 L/hour (SV=20.0 (time ⁻¹ )) to wash the resin. Next, 2 L of 60% ethanol aqueous solution (ethanol/water=60/40 (volume/volume)) as an elution solvent was passed through the resin column at a flow rate of 2 L/hour (SV=2.0 (time ⁻¹ )). . Subsequently, 2 L of purified water was passed through the resin column at a flow rate of 2 L/hour (SV = 2.0 (time ^-1 )) to elute the components adsorbed by the synthetic adsorbent. The fraction eluted from the resin column was concentrated under reduced pressure to about 10 times the concentration using a rotary evaporator, and freeze-dried overnight to obtain 40 g of brown powder as a bagasse decomposition extract. This was designated as extract W.

<Test Example 1: MMP-1 production inhibition test>
The inhibitory effect of extract A and extract W on MMP-1 production was investigated by evaluating the inhibitory effect of MMP-1 on normal human fibroblasts.

[Test Example 1-1]
As a medium for culturing normal human fibroblasts, 5% calf serum-containing Dulbecco's modified MEM medium (manufactured by Kurashiki Boseki Co., Ltd., hereinafter also referred to as "5% FBS-DMEM medium") was used. A medium containing 5% FBS-DMEM medium containing extract A at the concentration shown in Table 1 was prepared and used as a test sample-containing medium.

Normal human fibroblasts (manufactured by Kurashiki Boseki Co., Ltd.) were seeded together with 5% FBS-DMEM medium in a 96-well microplate at a density of 2.0×10 ⁴ cells/well. Twenty-four hours after seeding, the 5% FBS-DMEM medium in the microplates was replaced with extract A-containing test sample-containing medium. After culture for another 24 hours after medium replacement, the test sample-containing medium was replaced with Hank's buffer (containing Ca ²⁺ and Mg ²⁺ , HBS(+)). Immediately thereafter, the medium was replaced with fresh medium containing the test sample, and cultured for an additional 24 hours. After culturing, the culture supernatant was collected and subjected to ELISA.

ELISA was performed by the sandwich method, and was carried out by the following method. After adding Anti-human MMP-1 antibody to a high adsorption type ELISA plate, the plate was coated overnight at room temperature and then blocked with 1% bovine albumin (BSA) for 1 hour. After blocking, culture supernatant and MMP-1 for standard curve were added and incubated at room temperature for 2 hours, then Anti-human MMP-1 biotinylated antibody was added and incubated at room temperature for 1.5 hours. Furthermore, streptavidin-HRP was added and incubated at room temperature for 30 minutes. Then 0.3 mg/mL 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)-diammonium salt (ABTS) and 0.03% (V/V) hydrogen peroxide. Phosphate-citrate buffer solution (0.1 mol/L, pH 4.0) was added, reacted for 20 minutes, and absorbance at 405 nm was measured with a microplate reader.

The amount of MMP-1 in the culture supernatant was calculated from a calibration curve prepared using commercially available MMP-1. On the other hand, the cultured cells were lysed with 0.5% (V/V) Triton X-100 buffer, and the total protein was quantified by the BCA method. The amount of MMP-1 produced per unit amount of protein was calculated by dividing the amount of MMP-1 in the culture supernatant by the amount of total protein in the cells. Table 1 shows the results.

[Test Example 1-2]
In Test Example 1, after exchanging the test sample-containing medium with Hank's buffer solution (containing Ca ²⁺ , Mg ²⁺ , HBS(+)), after irradiating with ultraviolet A wave (UVA) at a dose of 4 J/cm ² , The amount of MMP-1 produced per unit amount of protein was calculated in the same manner as in Test Example 1, except that the medium was immediately replaced with a fresh medium containing the test sample. Table 1 shows the results.

[Test Example 1-3]
In Test Example 2, except that the extract A was changed to the extract W and the dose of ultraviolet A wave was changed to 5 J/cm ² , MMP- 1 production was calculated. Table 1 shows the results.

１）抽出物Ａ又は抽出物Ｗの濃度が０μｇ／ｍＬである試験例に対する有意差
＊：ｐ＜０．０５、有意な減少

1) Significant difference from test examples with extract A or extract W concentration of 0 μg/mL *: p<0.05, significant decrease

<Test Example 2: Elastase activity inhibition test>
The effect of extract A and extract W on inhibiting the elastase activity was examined by evaluating the effect of inhibiting the activity of normal human fibroblast-derived elastase.

[Test Example 2-1]
0.5% (V/V) Triton X-100 buffer ( ¹ mmol/L PMSF, 100 mmol/L Tris-HCl buffer, pH 8 .0) was added to lyse the cells, and this was used as a crude enzyme solution of fibroblast-derived elastase. Succinyl-L-alanyl-L-alanyl-L-alanine p-nitroanilide (Suc-Ala-Ala-Ala-pNA, 5 mmol/L, BACHEM AG) was used as a substrate for elastase. As a test solution, extract A was dissolved in Tris buffer to prepare a test solution with a predetermined concentration. EDTA at 6.25 mmol/L was used as a positive control.

50 μL of the test solution was added to each well of a 96-well microplate. Also, a 100 mmol/L Tris-HCl buffer (pH 8.0) containing 5 mmol/L Suc-Ala-Ala-Ala-pNA was prepared and added in 100 μL portions. 50 μL of the elastase crude enzyme solution was added to each well to obtain a reaction solution. The absorbance at 405 nm of the reaction solution immediately after addition of the crude elastase enzyme solution was measured as the absorbance before the reaction (blank absorbance). Then, the absorbance at 405 nm was measured for the reaction solution after standing at 37° C. for 2 hours for reaction (post-reaction absorbance). Using the value obtained by subtracting the blank absorbance from the absorbance after the reaction, the absorbance when the test solution is not added is C ', the absorbance when the test solution is added is S ', and the elastase activity inhibition rate (%) is obtained from the following formula. rice field. Table 2 shows the results. Extract A showed a significant elastase activity inhibitory effect at p<0.05.
Elastase inhibition rate (%) = (1-(S'/C')) x 100

[Test Example 2-2]
The elastase activity inhibition rate of Extract W was determined in the same manner as in Test Example 2-1, except that Extract A was changed to Extract W. 12.25 mmol/L EDTA was used as a positive control. Extract W was also found to have an inhibitory effect on elastase activity.

２）抽出物Ａの濃度が０μｇ／ｍＬである試験例に対する有意差
＊：ｐ＜０．０５、有意な減少

2) Significant difference from the test example with extract A concentration of 0 μg/mL *: p<0.05, significant decrease

<Test Example 3: Fibroblast activation test>
The activation effect of extract A on fibroblasts was examined by the MTT method.

As the medium for culturing normal human fibroblasts, the same medium as in Test Example 1 was used. Extract A was dissolved in water to prepare a medium containing 1% FBS-DMEM medium containing Extract A at the concentration shown in Table 3, and this medium was used as a test sample-containing medium. A 5% FBS-DMEM medium was used as a positive control.

Normal human fibroblasts (manufactured by Kurashiki Boseki Co., Ltd.) were seeded together with 5% FBS-DMEM medium in a 96-well microplate at a density of 2.0×10 ⁴ cells/well. Twenty-four hours after seeding, the 5% FBS-DMEM medium in the microplates was replaced with extract A-containing test sample-containing medium. After culture for an additional 48 hours after medium exchange, 1% FBS containing 0.4 mg/mL 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) - Changed to DMEM medium and cultured for 2 hours. The medium was removed and 2-propanol was added to extract the produced blue formazan. The absorbance of the extract at 550 nm was measured and used as the amount of blue formazan. The ratio (percentage) of the amount of blue formazan when using extract A to the amount of blue formazan produced when the concentration of extract A (based on the total amount of the medium containing the test sample) was 0 μg / mL (control) was calculated. was used as the cell activation rate. It can be said that the larger the value of the cell activation rate, the higher the cell activation effect. Table 3 shows the results.

３）抽出物Ａの濃度が０μｇ／ｍＬである試験例に対する有意差
＊：ｐ＜０．０５、有意な減少

3) Significant difference from test example with extract A concentration of 0 μg/mL *: p<0.05, significant decrease

Claims (9)

An anti-aging agent containing a bagasse decomposition extract as an active ingredient. 2. The decomposition extract of the bagasse according to claim 1, wherein the decomposition extract is a decomposition-treated liquid obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment and explosion treatment. anti-aging agent. 3. The anti-aging agent according to claim 2, wherein the decomposition extract of bagasse is a fraction obtained by passing the decomposition-treated liquid through a column packed with a fixed carrier. 4. The anti-aging agent according to claim 3, wherein said fixed carrier is a synthetic adsorbent or an ion exchange resin. The immobilizing carrier is a synthetic adsorbent, and the bagasse decomposition extract removes components adsorbed by the synthetic adsorbent with at least one solvent selected from the group consisting of water, methanol, ethanol, and mixtures thereof. 4. The anti-aging agent according to claim 3, which is a fraction obtained by elution. The antiaging agent according to claim 4 or 5, wherein the synthetic adsorbent is an aromatic resin, an acrylic methacrylic resin, or an acrylonitrile aliphatic resin. The bagasse decomposition extract is obtained by passing the decomposition treated liquid through a column filled with a synthetic adsorbent as a fixed carrier, and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water. is the fraction obtained by
The synthetic adsorbent is an unsubstituted aromatic resin,
The temperature of the column is 20-60° C.,
The anti-aging agent according to claim 2, wherein the mixed solvent has a volume ratio of ethanol and water (ethanol/water) of 50/50 to 60/40. 8. The anti-aging agent according to any one of claims 1 to 7, which is based on an extracellular matrix-degrading enzyme inhibitory action. The anti-aging agent according to any one of claims 1 to 7, which is based on fibroblast activation action.