WO2023234345A1 - External skin preparation containing unsaponified concentrate of rice bran oil - Google Patents

External skin preparation containing unsaponified concentrate of rice bran oil Download PDF

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Publication number
WO2023234345A1
WO2023234345A1 PCT/JP2023/020270 JP2023020270W WO2023234345A1 WO 2023234345 A1 WO2023234345 A1 WO 2023234345A1 JP 2023020270 W JP2023020270 W JP 2023020270W WO 2023234345 A1 WO2023234345 A1 WO 2023234345A1
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WO
WIPO (PCT)
Prior art keywords
skin
rice bran
concentrate
bran oil
present
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PCT/JP2023/020270
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French (fr)
Japanese (ja)
Inventor
京秀 周
優歩 山内
紀夫 中村
卓夫 築野
Original Assignee
築野グループ株式会社
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Publication of WO2023234345A1 publication Critical patent/WO2023234345A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/31—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63—Steroids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to an external preparation for skin containing a concentrate of rice bran oil unsaponifiables.
  • melanin production inhibitors such as ascorbic acid derivatives and hydroquinone derivatives
  • melanin production inhibitors and anti-inflammatory agents must be formulated at fairly high concentrations in order to obtain sufficient effects, so there are safety issues such as permanent pigment loss and carcinogenicity. be.
  • products such as arbutin have been developed and applied as skin whitening agents with excellent stability, but the problem is that the effects are slow and it is difficult to obtain an effect unless it is used continuously for a long period of time.
  • retinols which are blended for the purpose of preventing and improving wrinkles and sagging, have poor oxidation stability and are difficult to blend into formulations.
  • the inventors of the present application have been conducting research on the use of rice bran.
  • the deodorized scum generated when extracting and producing oil from rice bran contains tocopherols, tocotrienols, sterols and their fatty acid esters, squalene, etc. By removing fatty acids, components with physiological effects are concentrated. A method is shown (Patent Document 2).
  • An object of the present invention is to provide an external skin preparation that has both the effect of preventing or improving spots and freckles and the effect of improving skin elasticity.
  • the present invention includes the following inventions in order to solve the above problems.
  • the external skin preparation according to [1] which has the effect of reducing the amount of skin melanin and increasing skin elasticity.
  • the external skin preparation according to [3] which further has the effect of improving skin transparency.
  • a cosmetic product comprising the external skin preparation according to any one of [1] to [4].
  • a pharmaceutical product comprising the external skin preparation according to any one of [1] to [4].
  • an external preparation for skin that has both the effect of preventing or improving spots and freckles and the effect of improving skin elasticity.
  • FIG. 1 is a diagram showing changes in the amount of melanin from the start of the study in the rice bran oil unsaponifiable matter concentrate (lytrienol: RTN) group (squares) and the placebo group (circles).
  • FIG. 2 is a diagram showing changes in the transparency score (A) and texture score (B) from the start of the test in the RTN group (squares) and the placebo group (circles).
  • FIG. 3 is a diagram showing the amount of change in net viscoelasticity from the start of the test in the RTN group (squares) and the placebo group (circles).
  • FIG. 4 is a diagram showing changes in elasticity scores from the start of the study in the RTN group (squares) and the placebo group (circles).
  • the present invention provides a skin external preparation.
  • the skin external preparation of the present invention may be one containing a concentrate of rice bran oil unsaponifiables.
  • the rice bran oil unsaponifiables concentrate is not particularly limited as long as it is a concentrate of unsaponifiables obtained from rice bran.
  • rice bran oil unsaponifiable concentrate is an unsaponifiable product obtained by neutralizing and removing fatty acids from rice bran deodorized distillate, which is a by-product in the deodorizing process during the process of refining rice oil from rice bran. It may also be a concentrate.
  • the rice bran oil unsaponifiables concentrate may contain vitamin E (tocopherols, tocotrienols, etc.), sterols (phytosterols, triterpene alcohols, fatty acid esters thereof, etc.), squalene, and the like.
  • Sterol refers to a compound having a hydroxyl group at the 3-position among compounds (steroids) having a cyclopentanoperhydrophenanthrene skeleton (sterane skeleton). Sterols are generally widely distributed in the animal and plant kingdom in the form of free forms, ester forms, glycosides, etc., and are also important constituents of biological membranes.
  • the ester of a plant sterol and a fatty acid and/or the ester of a triterpene alcohol and a fatty acid contained in the external skin preparation of the present invention is an ester type sterol with a fatty acid.
  • the sterol may be an unsaturated compound having 27 to 30 carbon atoms and having one double bond at the 5/6 position, 7/8 position, 8/9 position or other position, It may also be a saturated compound obtained by hydrogenation.
  • plant sterols that are abundant in plants include ⁇ -sitosterol, stigmasterol, campesterol, and the like.
  • Triterpene alcohol is a sterol with 30 carbon atoms, and is a component abundantly contained in rice bran or rice oil.
  • the plant sterols and triterpene alcohols included in the sterols include those similar to those exemplified as sterols in the esters of plant sterols and fatty acids and/or esters of triterpene alcohols and fatty acids in the present invention.
  • the total content of fatty acid esters of plant sterols and/or fatty acid esters of triterpene alcohols in the rice bran oil unsaponifiables concentrate may be 3% by mass or more, 5% by mass or more, and 70% by mass or less, 60% by mass. % or less.
  • the content of plant sterols in the rice bran oil unsaponifiable matter concentrate may be 5% by mass or more and 20% by mass or less.
  • the content of tocopherol in the rice bran oil unsaponifiable matter concentrate may be 1% by mass or more and 5% by mass or less.
  • the content of tocotrienols in the rice bran oil unsaponifiable matter concentrate may be 1% by mass or more and 5% by mass or less.
  • the content of squalene in the rice bran oil unsaponifiables concentrate may be 1% by mass or more and 10% by mass or less.
  • the rice bran oil unsaponifiables concentrate may be a concentrate of unsaponifiables obtained in the process of extracting and refining oil from rice bran using a known method, and commercially available rice bran oil unsaponifiables concentrate It may be.
  • the method for obtaining rice bran oil unsaponifiables concentrate from rice bran is not particularly limited. For example, after producing rice bran oil using a known production method, the fatty acids contained in large amounts are extracted using the deodorized scum obtained in the deodorization process. Examples include a method of producing a fat-soluble rice bran oil unsaponifiable concentrate by deoxidizing the rice bran oil with a necessary minimum amount of alkali, a method described in JP-A No.
  • rice bran oil unsaponifiable concentrates examples include Rice Trienol (trade name) manufactured by Tsukino Foods Co., Ltd., and the like.
  • composition of the rice bran oil unsaponifiables concentrate is not limited, as an example, acid value: 0.8, squalene: 5.8 g, plant sterol: 10.1 g, triterpene alcohol: 5.2 g, Examples include those containing 3.7 g of tocopherol, 3.0 g of tocotrienol, and 10.0 g of fatty acid ester of plant sterol and fatty acid ester of triterpene alcohol.
  • the external skin preparation of the present invention has the effect of reducing the amount of skin melanin.
  • the method for confirming that the skin external preparation of the present invention has the effect of reducing the amount of skin melanin is not particularly limited, and the amount of melanin in the skin may be measured and evaluated by a known method. For example, it may be confirmed by measuring the density of melanin pigment in the skin.
  • the skin to be evaluated is irradiated with light of wavelengths of 660 nm and 880 nm using a Mexameter (manufactured by Courage+Khazaka), and the amount of melanin is calculated and confirmed from the ratio of the light reflected from the skin. There are several methods.
  • the external skin preparation of the present invention has the effect of increasing skin elasticity.
  • the method for confirming that the skin external preparation of the present invention has the effect of increasing skin elasticity is not particularly limited, and the elasticity of the skin may be measured and evaluated by a known method.
  • the viscoelastic modulus of the skin may be measured and confirmed by a known method, considering the skin as an elastic body, or by a visual analogue scale (VAS) questionnaire, etc. in accordance with a conventional method. Skin elasticity may be assessed and confirmed.
  • VAS visual analogue scale
  • the external skin preparation of the present invention may further have the effect of improving skin transparency.
  • the method for confirming that the skin external preparation of the present invention has the effect of improving skin transparency is not particularly limited, and confirmation may be made by measuring skin transparency using a known method, or by conducting a VAS questionnaire according to a conventional method.
  • the skin transparency may be evaluated and confirmed by the following methods.
  • Japanese Patent Application Publication No. 2004-215991 describes a method for evaluating skin transparency.
  • the form of the external skin preparation of the present invention is not particularly limited, and examples thereof include creams, ointments, gels, liniments, lotions, emulsions, powders, suspensions, aerosols, liquids, etc. It may also be a plaster, tape, poultice, plaster, etc. that is supported on the body.
  • the external skin preparation of the present invention may contain various main ingredients, auxiliary agents, and other additives that are commonly used in the production of external skin preparations, as long as they do not impair the effects of the present invention.
  • the skin external preparation of the present invention is not limited to one in which only rice bran oil unsaponifiable matter concentrate is the main ingredient, but may contain other pharmacological ingredients as the main ingredient.
  • the skin external preparation of the present invention can be implemented as a cosmetic product.
  • the cosmetics of the present invention can be manufactured by known methods.
  • the cosmetics of the present invention can be suitably used, for example, as whitening cosmetics.
  • the cosmetics of the present invention can be used to prevent and/or improve skin pigmentation such as age spots, freckles, dullness, and melasma, whiten the skin, and whiten the skin.
  • the form of the cosmetic product is not particularly limited.
  • skin care products such as lotion, cosmetic emulsion, cosmetic oil, serum, cream, cold cream, face wash, pack agent, sunscreen agent, aftershave lotion, shaving soap, body lotion, hand cream, leg cream;
  • Makeup supplies such as makeup base, foundation, concealer, face powder, water powder, face powder, Doran, eye shadow base, eye shadow, nose shadow, lip pencil, lipstick, lip balm, lip gloss, cheek blush; medicated cosmetics, soap , medicated soaps, body shampoos, cleaning products, bath salts, etc.
  • the cosmetics of the present invention may contain ingredients commonly used in cosmetics.
  • ingredients commonly used in cosmetics include, for example, purified water, alcohols (lower alcohols, polyhydric alcohols, etc.), oils and fats, waxes, bases such as hydrocarbons; surfactants, thickeners, viscosity Additives such as preparation agents, ultraviolet absorbers, ultraviolet scattering agents, ultraviolet shielding agents, stabilizers, pH adjusters, preservatives, colorants, fragrances, oily ingredients, silicones, fluorine oils, various skin nutrients; blood Examples include, but are not limited to, glidant agents, bactericidal agents, anti-inflammatory agents, cell activators, vitamins, amino acids, humectants, keratolytic agents, polymer compounds, and the like.
  • the cosmetics of the present invention may further contain other active ingredients within a range that does not impair the effects of the present invention.
  • active ingredients include antioxidant ingredients, anti-aging ingredients, anti-inflammatory ingredients, anti-sagging ingredients, whitening ingredients, cell activation ingredients, blood circulation promoting ingredients, moisturizing ingredients, and DNA damage prevention and/or repair effects.
  • anti-glycation components, peptides or derivatives thereof, amino acids or derivatives thereof, etc. are not limited to these.
  • the skin external preparation of the present invention can be implemented as a pharmaceutical product.
  • the pharmaceutical product of the present invention can be manufactured by a known method.
  • the form of the drug is not particularly limited. For example, solutions, emulsions, suspensions, creams, ointments, gels, liniments, lotions, aerosols, powders, plasters with a base supported on a support, tapes, poultices, and plasters. agents, etc.
  • the pharmaceutical product of the present invention may contain a pharmaceutically acceptable carrier or additive in addition to the skin external preparation of the present invention.
  • the blending ratio of carriers or additives may be appropriately set based on the range normally employed in the pharmaceutical field.
  • the carriers or additives that can be incorporated are not particularly limited, and include various carriers such as water, physiological saline, other aqueous solvents, aqueous or oily bases, excipients, binders, pH adjusters, disintegrants, and absorbents. Examples include, but are not limited to, various additives such as accelerators, lubricants, colorants, and fragrances.
  • the pharmaceutical product of the present invention may further contain other active ingredients to the extent that the effects of the present invention are not impaired.
  • active ingredients include antioxidant ingredients, anti-aging ingredients, anti-inflammatory ingredients, anti-sagging ingredients, whitening ingredients, cell activation ingredients, blood circulation promoting ingredients, moisturizing ingredients, and DNA damage prevention and/or repair effects. , anti-glycation components, peptides or derivatives thereof, amino acids or derivatives thereof, etc., but are not limited to these.
  • the skin external preparation of the present invention can be referred to as an agent for reducing the amount of skin melanin.
  • the skin external preparation of the present invention can be referred to as a skin elasticity improving agent.
  • the skin external preparation of the present invention can be referred to as an agent for improving skin transparency.
  • the content of the rice bran oil unsaponifiables concentrate contained in the skin external preparation of the present invention is set to such an extent that upon application, the effects of reducing the amount of skin melanin, increasing skin elasticity, and/or improving skin transparency can be obtained.
  • it may be 0.01% by mass or more, 0.1% by mass or more, 1% by mass or more, or 10% by mass or more with respect to the entire skin external preparation of the present invention.
  • the upper limit of the content of rice bran oil unsaponifiables concentrate contained in the skin external preparation of the present invention is not particularly limited, and for example, 100% by mass or less, 95% by mass or less, 90% by mass or less, 80% by mass or less , 70% by mass or less.
  • the rice bran oil unsaponifiables concentrate used in the present invention contains ⁇ -oryzanol, ferulic acid, wax, glucoside ceramide, etc., which are components contained in common rice bran oil. Therefore, the skin external preparation of the present invention reduces the amount of skin melanin and/or improves skin elasticity due to the synergistic effect of the ingredients contained in the rice bran oil unsaponifiables concentrate and other ingredients contained in the rice bran oil. It is thought that this has an excellent effect of increasing skin transparency and/or improving skin transparency.
  • the animal to which the skin external preparation of the present invention is applied is not particularly limited, and may be, for example, a human or a non-human animal.
  • the parts of animals on which the external skin preparation of the present invention is effective are not particularly limited, and include, for example, the skin of the face (forehead, cheeks, etc.), arms, legs, etc.
  • the frequency of use of the skin external preparation of the present invention is not particularly limited, and includes, for example, once or more a day, 1 to 3 times a day, etc.
  • the period of use of the skin external preparation of the present invention is not particularly limited, and may be, for example, one week or more, two weeks or more, or four weeks or more.
  • the daily usage amount of the skin external preparation of the present invention is not particularly limited, and may be, for example, 1 mg or more, 10 mg or more, 100 mg or more in terms of rice bran oil unsaponifiables concentrate.
  • the upper limit of the recommended daily usage amount is not particularly limited, and may be, for example, 1000 mg in terms of rice bran oil unsaponifiables concentrate.
  • Creams of Example 1 and Comparative Example 1 were prepared by mixing the reagents shown in Table 1 below.
  • rice bran oil unsaponifiables concentrate (trade name: Rice Trienol, manufactured by Tsukino Foods Co., Ltd.) or the same amount of purified water was used.
  • Table 1 shows the composition per 100 g of each test cream.
  • Example 1 Preparation of test creams
  • Each cream of Example 1 and Comparative Example 1 was prepared according to the following procedure.
  • (1) Glycerin was added to purified water and dissolved by heating in an 80°C water bath (TBM204AA, manufactured by Advantech Co., Ltd.).
  • Second Methylparaben was added to BG and dissolved by heating in a water bath at 80°C.
  • the reagents used in the above test cream are as follows. ⁇ Purified water (manufacturer: Organo Co., Ltd.) ⁇ BG (Product name: 1,3-butylene glycol, Manufacturer: Daicel Corporation) ⁇ Methylparaben (Product name: NIPAGIN M, Manufacturer: Clariant Japan Co., Ltd.) ⁇ Glycerin (Product name: Concentrated glycerin for cosmetics, Manufacturer: Kao Corporation) ⁇ Rice bran oil unsaponifiables concentrate (Product name: Rice Trienol (RTN), Manufacturer: Tsukino Foods Co., Ltd.) ⁇ Triethylhexanoin (Product name: FineNeo-IOTG, Manufacturer: Nippon Fine Chemical Co., Ltd.) ⁇ Dimethicone (Product name: DOWSIL SH 200 C Fluid 6cs, Manufacturer: Dow Chemical Japan Co., Ltd.) ⁇ Glyceryl stearate (Product name: NIKK
  • Test method 3.1 Test overview The test was conducted under the following conditions. Test method: Placebo-controlled, single-blind test Participants: Females in their 20s to 50s Number of subjects: 22 (one of them dropped out after 8 weeks) Sample: 1% RTN combination cream (RTN 1g/100g) (see Example 1, Table 1) or placebo cream (purified water 1g/100g) (Comparative Example 1, see Table 1) How to use: Apply approximately 0.4 g/time of 1% RTN cream to the right half of the face twice a day, and at the same time apply the same amount of placebo cream to the left half of the face Test period: 3 months Number of tests: 4 times (before the start of the test (0th week), during the test (4th week, 8th week, 12th week))
  • VAS Visual Analogue Scale
  • the viscoelastic probe (Cutometer CT 580 MP, probe diameter 6 mm, manufactured by Courage + Khazaka) of the skin viscoelasticity measuring device (Cutometer Dual MPA 580, manufactured by Courage + Khazaka) was brought into contact with the skin of the cheekbone, and The net viscoelasticity was measured by applying pressure (450 mbar, suction time 3 seconds, relaxation time 3 seconds). Each subject was measured three times on each side, and the average value was taken as the value for each subject. Student's t-test was used for statistical processing.
  • the subjects waited in a constant temperature and humidity room for 20 minutes, and while their skin was acclimatizing, they filled out the VAS questionnaire.
  • the test subjects were shown a 10 cm long line (the left end being ⁇ very poor'' and the right end being ⁇ very good''), and asked to indicate on the line how much they felt about their skin's elasticity at the time of the test. The average distance from "very poor" for each test date was calculated. Dunnet's test and Student's t-test were used for statistical processing.
  • FIG. 1 is a diagram showing the amount of change in the amount of melanin when the amount of melanin before the start of the test is set to 0. Immediately after the start of the study, a decrease in the amount of melanin was observed in both the RTN group (squares) and the placebo group (circles). In the placebo group, the change in melanin amount started to increase from week 8 to week 12, whereas in the RTN group, it continued to significantly decrease from the start of the study until week 12. A significant difference between groups was observed at week 12 (p ⁇ 0.01).
  • FIG. 2 is a diagram showing the amount of change when the degree of transparency (FIG. 2A) and texture (FIG. 2B) before the start of the test is set to 0.
  • FIG. 2A degree of transparency
  • FIG. 2B texture
  • FIG. 2A degree of transparency
  • FIG. 2B texture
  • FIG. 3 is a diagram showing the amount of change in net viscoelasticity when the net viscoelasticity (R5) before the start of the test is set to 0.
  • RTN group squares
  • the net viscoelasticity increased from the start of the test to the 4th week, and then maintained a gradual increase until the 12th week.
  • FIG. 4 is a diagram showing the amount of change when the level of elasticity sensation before the start of the test is set to 0.
  • RTN group squares
  • a significant improvement was observed in the perceived elasticity compared to before the start of the study, and a significant improvement was observed compared to the placebo group. Furthermore, the improved condition was maintained until the 12th week.

Abstract

The present invention provides an external skin preparation which contains an unsaponified concentrate of rice bran oil and has both the effect of preventing or ameliorating blemishes and freckles and the effect of ameliorating skin elasticity.

Description

米糠油不ケン化物濃縮物を含む皮膚外用剤External skin preparation containing rice bran oil unsaponifiables concentrate
　本発明は、米糠油不ケン化物濃縮物を含む皮膚外用剤に関する。 The present invention relates to an external preparation for skin containing a concentrate of rice bran oil unsaponifiables.
　皮膚の色素沈着であるシミやソバカスは、紫外線等の刺激や、ホルモン分泌の異常、メラニン代謝の異常等の原因により表皮の基底膜に局在するメラノサイトが異常活性化して過剰なメラニン色素を合成し、そのメラニン色素が皮膚内に異常沈着することにより生じるものと考えられている（特許文献１）。日焼けのように一時的に作られるメラニンは消えていくが、シミやソバカスは継続的にメラニンが過剰に作られている状態である。また、紫外線による影響は、色素沈着や炎症だけでなく乾燥や落屑を起こし、長期的にはいわゆる光老化と呼ばれるしわやたるみの発生につながる。 Spots and freckles, which are skin pigmentations, occur when melanocytes localized in the basement membrane of the epidermis become abnormally activated and synthesize excessive melanin due to stimulation such as ultraviolet rays, abnormal hormone secretion, abnormal melanin metabolism, etc. However, it is thought that the melanin pigment is abnormally deposited within the skin (Patent Document 1). Melanin that is produced temporarily, like when you get a sunburn, disappears, but age spots and freckles are a state where melanin is continuously produced in excess. In addition, the effects of ultraviolet rays cause not only pigmentation and inflammation, but also dryness and scaling, which in the long term leads to the appearance of wrinkles and sagging, a condition known as photoaging.
　皮膚の色素沈着、特にシミやソバカスの予防や症状改善を目的として、アスコルビン酸誘導体や、ハイドロキノン誘導体など種々のメラニン生成抑制剤が提案され、それらを配合した皮膚外用剤が市販されている。しかしながら、上記のメラニン生成抑制剤や抗炎症剤は、十分な効果を得るためにはかなりの高濃度を配合しなければならないため、永久的な色素脱出や発がん性といった安全性の面で問題がある。近年では安定性に優れた皮膚美白用剤としてアルブチンなどが開発応用されているが効果が緩徐で、長期間連用しないと効果が得られにくいという課題がある。また、しわやたるみの予防および改善等の目的で配合されるレチノール類については、酸化安定性が悪く、製剤中に配合することが難しいことが知られている。 A variety of melanin production inhibitors, such as ascorbic acid derivatives and hydroquinone derivatives, have been proposed for the purpose of preventing skin pigmentation, especially spots and freckles, and improving symptoms, and external skin preparations containing these are commercially available. However, the above-mentioned melanin production inhibitors and anti-inflammatory agents must be formulated at fairly high concentrations in order to obtain sufficient effects, so there are safety issues such as permanent pigment loss and carcinogenicity. be. In recent years, products such as arbutin have been developed and applied as skin whitening agents with excellent stability, but the problem is that the effects are slow and it is difficult to obtain an effect unless it is used continuously for a long period of time. Furthermore, it is known that retinols, which are blended for the purpose of preventing and improving wrinkles and sagging, have poor oxidation stability and are difficult to blend into formulations.
　本願発明者らは米糠の利用について研究を行ってきた。米糠から油を抽出・生成するうえで発生する脱臭スカムには、トコフェロールやトコトリエノール、ステロール及びその脂肪酸エステル体、スクワレン等が含まれており、脂肪酸を除去することで生理作用を有する成分を濃縮する方法が示されている（特許文献２）。 The inventors of the present application have been conducting research on the use of rice bran. The deodorized scum generated when extracting and producing oil from rice bran contains tocopherols, tocotrienols, sterols and their fatty acid esters, squalene, etc. By removing fatty acids, components with physiological effects are concentrated. A method is shown (Patent Document 2).
特開２０２１－１１６２７９号公報JP 2021-116279 Publication 特開２００５－２５５７４６号公報Japanese Patent Application Publication No. 2005-255746
　本発明は、シミやソバカスを予防または改善する作用と、皮膚弾力を改善する作用の両方を有する皮膚外用剤を提供することを課題とする。 An object of the present invention is to provide an external skin preparation that has both the effect of preventing or improving spots and freckles and the effect of improving skin elasticity.
　本発明は、上記の課題を解決するために、以下の各発明を包含する。
［１］米糠油不ケン化物濃縮物を含有する皮膚外用剤。
［２］米糠油不ケン化物濃縮物が、植物ステロール、トコフェロール、トコトリエノールおよびスクワレンを含む、［１］に記載の皮膚外用剤。
［３］皮膚メラニン量の減少および皮膚弾力の増加の作用を有する、［１］に記載の皮膚外用剤。
［４］さらに皮膚透明感の改善の作用を有する、［３］に記載の皮膚外用剤。
［５］［１］～［４］のいずれか一項に記載の皮膚外用剤を含むことを特徴とする化粧品。
［６］［１］～［４］のいずれか一項に記載の皮膚外用剤を含むことを特徴とする医薬品。
［７］米糠油不ケン化物濃縮物を含有する皮膚メラニン量の減少剤。
［８］米糠油不ケン化物濃縮物を含有する皮膚弾力の改善剤。
［９］米糠油不ケン化物濃縮物を含有する皮膚透明感の改善剤。 The present invention includes the following inventions in order to solve the above problems.
[1] A skin external preparation containing a concentrate of rice bran oil unsaponifiables.
[2] The skin external preparation according to [1], wherein the rice bran oil unsaponifiables concentrate contains plant sterols, tocopherols, tocotrienols, and squalene.
[3] The external skin preparation according to [1], which has the effect of reducing the amount of skin melanin and increasing skin elasticity.
[4] The external skin preparation according to [3], which further has the effect of improving skin transparency.
[5] A cosmetic product comprising the external skin preparation according to any one of [1] to [4].
[6] A pharmaceutical product comprising the external skin preparation according to any one of [1] to [4].
[7] A skin melanin amount reducing agent containing a concentrate of rice bran oil unsaponifiables.
[8] A skin elasticity improving agent containing a concentrate of rice bran oil unsaponifiables.
[9] A skin transparency improving agent containing a concentrate of rice bran oil unsaponifiables.
　本発明により、シミやソバカスを予防または改善する作用と、皮膚弾力を改善する作用の両方を有する皮膚外用剤を提供することができる。 According to the present invention, it is possible to provide an external preparation for skin that has both the effect of preventing or improving spots and freckles and the effect of improving skin elasticity.
図１は、米糠油不ケン化物濃縮物（ライストリエノール：ＲＴＮ）群（四角）およびプラセボ群（丸）における試験開始時からのメラニン量の変化を示す図である。FIG. 1 is a diagram showing changes in the amount of melanin from the start of the study in the rice bran oil unsaponifiable matter concentrate (lytrienol: RTN) group (squares) and the placebo group (circles). 図２は、ＲＴＮ群（四角）およびプラセボ群（丸）における試験開始時からの透明感スコア（Ａ）およびキメスコア（Ｂ）の変化を示す図である。FIG. 2 is a diagram showing changes in the transparency score (A) and texture score (B) from the start of the test in the RTN group (squares) and the placebo group (circles). 図３は、ＲＴＮ群（四角）およびプラセボ群（丸）における試験開始時からの正味粘弾性の変化量を示す図である。FIG. 3 is a diagram showing the amount of change in net viscoelasticity from the start of the test in the RTN group (squares) and the placebo group (circles). 図４は、ＲＴＮ群（四角）およびプラセボ群（丸）における試験開始時からの弾力スコアの変化を示す図である。FIG. 4 is a diagram showing changes in elasticity scores from the start of the study in the RTN group (squares) and the placebo group (circles).
〔皮膚外用剤〕
　本発明は、皮膚外用剤を提供する。本発明の皮膚外用剤は、米糠油不ケン化物濃縮物を含有するものであればよい。 [Skin external preparation]
The present invention provides a skin external preparation. The skin external preparation of the present invention may be one containing a concentrate of rice bran oil unsaponifiables.
　米糠油不ケン化物濃縮物は、米糠から得られる不ケン化物を濃縮したものであればよく、特に限定されない。本発明において、米糠油不ケン化物濃縮物は、米糠から米油を精製する過程での脱臭工程において副生する米油脱臭留出物から脂肪酸を中和し除去することで得られる不ケン化物の濃縮物であってもよい。米糠油不ケン化物濃縮物には、ビタミンＥ類（トコフェロール、トコトリエノール等）、ステロール類（植物ステロール、トリテルペンアルコール、それらの脂肪酸エステル等）、スクワレン等が含まれていてもよい。 The rice bran oil unsaponifiables concentrate is not particularly limited as long as it is a concentrate of unsaponifiables obtained from rice bran. In the present invention, rice bran oil unsaponifiable concentrate is an unsaponifiable product obtained by neutralizing and removing fatty acids from rice bran deodorized distillate, which is a by-product in the deodorizing process during the process of refining rice oil from rice bran. It may also be a concentrate. The rice bran oil unsaponifiables concentrate may contain vitamin E (tocopherols, tocotrienols, etc.), sterols (phytosterols, triterpene alcohols, fatty acid esters thereof, etc.), squalene, and the like.
　ステロールとは、シクロペンタノペルヒドロフェナントレン骨格（ステラン骨格）を有する化合物（ステロイド）のうち、３位に水酸基を有する化合物をいう。ステロールは、通常、遊離状、エステル型、配糖体等の形で、動植物界に幅広く分布しており、生体膜の重要な構成成分でもある。本発明の皮膚外用剤に含有される植物ステロールと脂肪酸とのエステルおよび／またはトリテルペンアルコールと脂肪酸とのエステルは、脂肪酸とのエステル型のステロールである。 Sterol refers to a compound having a hydroxyl group at the 3-position among compounds (steroids) having a cyclopentanoperhydrophenanthrene skeleton (sterane skeleton). Sterols are generally widely distributed in the animal and plant kingdom in the form of free forms, ester forms, glycosides, etc., and are also important constituents of biological membranes. The ester of a plant sterol and a fatty acid and/or the ester of a triterpene alcohol and a fatty acid contained in the external skin preparation of the present invention is an ester type sterol with a fatty acid.
　ステロールは、炭素数２７～３０であり、１個の二重結合を５／６位、７／８位、８／９位またはその他の位置に有している不飽和化合物であってもよく、水素化により得られる飽和化合物であってもよい。ステロールのうち植物に多く存在する植物ステロールとしては、β－シトステロール、スチグマステロール、カンペステロール等が挙げられる。トリテルペンアルコールは、炭素数３０のステロールであり、米糠または米油中に多く含まれる成分である。 The sterol may be an unsaturated compound having 27 to 30 carbon atoms and having one double bond at the 5/6 position, 7/8 position, 8/9 position or other position, It may also be a saturated compound obtained by hydrogenation. Among sterols, plant sterols that are abundant in plants include β-sitosterol, stigmasterol, campesterol, and the like. Triterpene alcohol is a sterol with 30 carbon atoms, and is a component abundantly contained in rice bran or rice oil.
　ステロール類に含まれる植物ステロールおよびトリテルペンアルコールとしては、本発明における植物ステロールと脂肪酸とのエステルおよび／またはトリテルペンアルコールと脂肪酸とのエステルにおいて、ステロールとして例示したものと同様のものが挙げられる。 The plant sterols and triterpene alcohols included in the sterols include those similar to those exemplified as sterols in the esters of plant sterols and fatty acids and/or esters of triterpene alcohols and fatty acids in the present invention.
　米糠油不ケン化物濃縮物中の植物ステロールの脂肪酸エステルおよび／またはトリテルペンアルコールの脂肪酸エステルの合計含有量は、３質量％以上、５質量％以上であってもよく、７０質量％以下、６０質量％以下であってもよい。米糠油不ケン化物濃縮物中の植物ステロールの含有量は、５質量％以上であってもよく、２０質量％以下であってもよい。米糠油不ケン化物濃縮物中のトコフェロールの含有量は、１質量％以上であってもよく、５質量％以下であってもよい。米糠油不ケン化物濃縮物中のトコトリエノールの含有量は、１質量％以上であってもよく、５質量％以下であってもよい。米糠油不ケン化物濃縮物中のスクワレンの含有量は、１質量％以上であってもよく、１０質量％以下であってもよい。 The total content of fatty acid esters of plant sterols and/or fatty acid esters of triterpene alcohols in the rice bran oil unsaponifiables concentrate may be 3% by mass or more, 5% by mass or more, and 70% by mass or less, 60% by mass. % or less. The content of plant sterols in the rice bran oil unsaponifiable matter concentrate may be 5% by mass or more and 20% by mass or less. The content of tocopherol in the rice bran oil unsaponifiable matter concentrate may be 1% by mass or more and 5% by mass or less. The content of tocotrienols in the rice bran oil unsaponifiable matter concentrate may be 1% by mass or more and 5% by mass or less. The content of squalene in the rice bran oil unsaponifiables concentrate may be 1% by mass or more and 10% by mass or less.
　米糠油不ケン化物濃縮物は、米糠から公知の方法を用いて油を抽出・精製する過程で得られた不ケン化物を濃縮したものであってもよく、市販の米糠油不ケン化物濃縮物であってもよい。米糠から米糠油不ケン化物濃縮物を得る方法は、特に限定されず、例えば、公知の製造方法を用いて米糠油を製造した後、脱臭工程で得られる脱臭スカムを用いて多量に含まれる脂肪酸を必要最小限のアルカリによって脱酸することで脂溶性の米糠油不ケン化物濃縮物を製造する方法、特開２００５－２５５７４６号公報に記載の方法などが挙げられる。市販の米糠油不ケン化物濃縮物としては、例えば築野食品工業株式会社製のライストリエノール（商品名）等が挙げられる。米糠油不ケン化物濃縮物の組成を限定するものではないが、一例としては、酸価：０．８であり、スクワレン：５．８ｇ、植物ステロール：１０．１ｇ、トリテルペンアルコール：５．２ｇ、トコフェロール：３．７ｇ、トコトリエノール：３．０ｇ、植物ステロールの脂肪酸エステルおよびトリテルペンアルコールの脂肪酸エステル：１０．０ｇを含有するものが挙げられる。 The rice bran oil unsaponifiables concentrate may be a concentrate of unsaponifiables obtained in the process of extracting and refining oil from rice bran using a known method, and commercially available rice bran oil unsaponifiables concentrate It may be. The method for obtaining rice bran oil unsaponifiables concentrate from rice bran is not particularly limited. For example, after producing rice bran oil using a known production method, the fatty acids contained in large amounts are extracted using the deodorized scum obtained in the deodorization process. Examples include a method of producing a fat-soluble rice bran oil unsaponifiable concentrate by deoxidizing the rice bran oil with a necessary minimum amount of alkali, a method described in JP-A No. 2005-255746, and the like. Examples of commercially available rice bran oil unsaponifiable concentrates include Rice Trienol (trade name) manufactured by Tsukino Foods Co., Ltd., and the like. Although the composition of the rice bran oil unsaponifiables concentrate is not limited, as an example, acid value: 0.8, squalene: 5.8 g, plant sterol: 10.1 g, triterpene alcohol: 5.2 g, Examples include those containing 3.7 g of tocopherol, 3.0 g of tocotrienol, and 10.0 g of fatty acid ester of plant sterol and fatty acid ester of triterpene alcohol.
　本発明の皮膚外用剤は、皮膚メラニン量の減少の作用を有する。本発明の皮膚外用剤が皮膚メラニン量の減少の作用を有することを確認する方法は特に限定されず、公知の手法により皮膚のメラニン量を測定し評価すればよい。例えば、皮膚のメラニン色素の濃さを測定して確認してもよい。具体例としては、メキサメータ（Ｍｅｘａｍｅｔｅｒ、Ｃｏｕｒａｇｅ＋Ｋｈａｚａｋａ社製）を用いて評価対象である皮膚において６６０ｎｍおよび８８０ｎｍの波長の光を照射し、皮膚から反射された光の比からメラニン量を算出して確認する方法が挙げられる。 The external skin preparation of the present invention has the effect of reducing the amount of skin melanin. The method for confirming that the skin external preparation of the present invention has the effect of reducing the amount of skin melanin is not particularly limited, and the amount of melanin in the skin may be measured and evaluated by a known method. For example, it may be confirmed by measuring the density of melanin pigment in the skin. As a specific example, the skin to be evaluated is irradiated with light of wavelengths of 660 nm and 880 nm using a Mexameter (manufactured by Courage+Khazaka), and the amount of melanin is calculated and confirmed from the ratio of the light reflected from the skin. There are several methods.
　本発明の皮膚外用剤は、皮膚弾力の増加の作用を有する。本発明の皮膚外用剤が皮膚弾力の増加の作用を有することを確認する方法は特に限定されず、公知の手法により皮膚の弾力性を測定し評価すればよい。例えば、皮膚を一つの弾性体であるとみなして、公知の手法により皮膚の粘弾性率を測定して確認してもよく、常法に従って視覚的アナログスケール（ＶＡＳ、Ｖｉｓｕａｌ　Ａｎａｌｏｇｕｅ　Ｓｃａｌｅ）アンケート等により皮膚弾力を評価し確認してもよい。具体例としては、キュートメータ（Ｃｕｔｏｍｅｔｅｒ、Ｃｏｕｒａｇｅ＋Ｋｈａｚａｋａ社製）を用いて、評価対象である皮膚において陰圧により皮膚を一定時間吸引し、その後陰圧解除して皮膚の変形する程度および該変形が元に戻る程度を数値化し、皮膚の粘弾性を測定して確認する方法が挙げられる。 The external skin preparation of the present invention has the effect of increasing skin elasticity. The method for confirming that the skin external preparation of the present invention has the effect of increasing skin elasticity is not particularly limited, and the elasticity of the skin may be measured and evaluated by a known method. For example, the viscoelastic modulus of the skin may be measured and confirmed by a known method, considering the skin as an elastic body, or by a visual analogue scale (VAS) questionnaire, etc. in accordance with a conventional method. Skin elasticity may be assessed and confirmed. As a specific example, using a Cutometer (manufactured by Courage+Khazaka), negative pressure is applied to the skin to be evaluated for a certain period of time, and then the negative pressure is released to determine the degree of deformation of the skin and the origin of the deformation. One way to confirm this is by quantifying the extent to which the skin returns to normal and measuring the viscoelasticity of the skin.
　本発明の皮膚外用剤は、皮膚透明感の改善の作用をさらに有していてもよい。本発明の皮膚外用剤が皮膚透明感の改善の作用を有することを確認する方法は特に限定されず、公知の手法により皮膚の透明感を測定して確認してもよく、常法に従ってＶＡＳアンケート等により皮膚透明感を評価し確認してもよい。例えば、特開２００４－２１５９９１号公報には、皮膚の透明感評価方法について記載されている。 The external skin preparation of the present invention may further have the effect of improving skin transparency. The method for confirming that the skin external preparation of the present invention has the effect of improving skin transparency is not particularly limited, and confirmation may be made by measuring skin transparency using a known method, or by conducting a VAS questionnaire according to a conventional method. The skin transparency may be evaluated and confirmed by the following methods. For example, Japanese Patent Application Publication No. 2004-215991 describes a method for evaluating skin transparency.
　本発明の皮膚外用剤の形態は特に限定されず、例えば、クリーム剤、軟膏剤、ゲル剤、リニメント剤、ローション剤、乳剤、粉剤、懸濁剤、エアゾール剤、液剤等や、基剤を支持体上に支持させた硬膏剤、テープ剤、パップ剤、プラスター剤等であってもよい。 The form of the external skin preparation of the present invention is not particularly limited, and examples thereof include creams, ointments, gels, liniments, lotions, emulsions, powders, suspensions, aerosols, liquids, etc. It may also be a plaster, tape, poultice, plaster, etc. that is supported on the body.
　本発明の皮膚外用剤は、本発明の効果を損なわない限り、皮膚外用剤の製造に通常使用される各種主剤、助剤およびその他添加剤等を含んでいてもよい。本発明の皮膚外用剤は、米糠油不ケン化物濃縮物のみが主剤となるものに限られず、他の薬理成分が主剤として含まれていてもよい。 The external skin preparation of the present invention may contain various main ingredients, auxiliary agents, and other additives that are commonly used in the production of external skin preparations, as long as they do not impair the effects of the present invention. The skin external preparation of the present invention is not limited to one in which only rice bran oil unsaponifiable matter concentrate is the main ingredient, but may contain other pharmacological ingredients as the main ingredient.
　本発明の皮膚外用剤は、化粧品として実施することができる。本発明の化粧品は、公知の手法により製造することができる。本発明の化粧品は、例えば美白用化粧品として好適に用いることができる。本発明の化粧品は、シミ、ソバカス、クスミ、肝斑等の皮膚の色素沈着の予防および／または改善、皮膚の美白、ホワイトニング等に用いることができる。 The skin external preparation of the present invention can be implemented as a cosmetic product. The cosmetics of the present invention can be manufactured by known methods. The cosmetics of the present invention can be suitably used, for example, as whitening cosmetics. The cosmetics of the present invention can be used to prevent and/or improve skin pigmentation such as age spots, freckles, dullness, and melasma, whiten the skin, and whiten the skin.
　本発明において、化粧品の形態は特に限定されない。例えば、化粧水、化粧用乳液、化粧用オイル、美容液、クリーム、コールドクリーム、洗顔料、パック剤、サンスクリーン剤、アフターシェーブローション、シェービングソープ、ボディローション、ハンドクリーム、レッグクリーム等のスキンケア用品；化粧下地、ファウンデーション、コンシーラー、フェイスパウダー、水おしろい、おしろい、ドーラン、アイシャドーベース、アイシャドー、ノーズシャドー、リップペンシル、口紅、リップクリーム、リップグロス、頬紅等のメイクアップ用品；薬用化粧料、石鹸、薬用石鹸、ボディシャンプー、洗浄料、入浴剤等が挙げられる。 In the present invention, the form of the cosmetic product is not particularly limited. For example, skin care products such as lotion, cosmetic emulsion, cosmetic oil, serum, cream, cold cream, face wash, pack agent, sunscreen agent, aftershave lotion, shaving soap, body lotion, hand cream, leg cream; Makeup supplies such as makeup base, foundation, concealer, face powder, water powder, face powder, Doran, eye shadow base, eye shadow, nose shadow, lip pencil, lipstick, lip balm, lip gloss, cheek blush; medicated cosmetics, soap , medicated soaps, body shampoos, cleaning products, bath salts, etc.
　本発明の化粧品は、本発明の皮膚外用剤に加えて、通常化粧品に用いられる成分を含有していてもよい。そのような成分の具体例として、例えば、精製水、アルコール類（低級アルコール、多価アルコール等）、油脂類、ロウ類、炭化水素類のような基剤；界面活性剤、増粘剤、粘度調製剤、紫外線吸収剤、紫外線散乱剤、紫外線遮蔽剤、安定剤、ｐＨ調整剤、防腐剤、着色剤、香料、油性成分、シリコーン類、フッ素系油剤、各種皮膚栄養剤等の添加剤；血流促進剤、殺菌剤、消炎剤、細胞賦活剤、ビタミン類、アミノ酸、保湿剤、角質溶解剤、高分子化合物等が挙げられるがこれらに限定されない。 In addition to the skin external preparation of the present invention, the cosmetics of the present invention may contain ingredients commonly used in cosmetics. Specific examples of such components include, for example, purified water, alcohols (lower alcohols, polyhydric alcohols, etc.), oils and fats, waxes, bases such as hydrocarbons; surfactants, thickeners, viscosity Additives such as preparation agents, ultraviolet absorbers, ultraviolet scattering agents, ultraviolet shielding agents, stabilizers, pH adjusters, preservatives, colorants, fragrances, oily ingredients, silicones, fluorine oils, various skin nutrients; blood Examples include, but are not limited to, glidant agents, bactericidal agents, anti-inflammatory agents, cell activators, vitamins, amino acids, humectants, keratolytic agents, polymer compounds, and the like.
　本発明の化粧品は、本発明の効果を損なわない範囲で、その他の有効成分をさらに含んでいてもよい。有効成分の具体例として、例えば、抗酸化成分、老化防止成分、抗炎症成分、抗たるみ成分、美白成分、細胞賦活化成分、血行促進成分、保湿成分、ＤＮＡの損傷の予防および／または修復作用を有する成分、抗糖化成分、ペプチドまたはその誘導体、アミノ酸またはその誘導体等が挙げられるがこれらに限定されない。 The cosmetics of the present invention may further contain other active ingredients within a range that does not impair the effects of the present invention. Specific examples of active ingredients include antioxidant ingredients, anti-aging ingredients, anti-inflammatory ingredients, anti-sagging ingredients, whitening ingredients, cell activation ingredients, blood circulation promoting ingredients, moisturizing ingredients, and DNA damage prevention and/or repair effects. , anti-glycation components, peptides or derivatives thereof, amino acids or derivatives thereof, etc., but are not limited to these.
　本発明の皮膚外用剤は、医薬品として実施することができる。本発明の医薬品は、公知の手法により製造することができる。本発明において、医薬品の形態は特に限定されない。例えば、液剤、乳剤、懸濁剤、クリーム剤、軟膏剤、ゲル剤、リニメント剤、ローション剤、エアゾール剤、粉剤、基剤を支持体上に支持させた硬膏剤、テープ剤、パップ剤、プラスター剤等が挙げられる。 The skin external preparation of the present invention can be implemented as a pharmaceutical product. The pharmaceutical product of the present invention can be manufactured by a known method. In the present invention, the form of the drug is not particularly limited. For example, solutions, emulsions, suspensions, creams, ointments, gels, liniments, lotions, aerosols, powders, plasters with a base supported on a support, tapes, poultices, and plasters. agents, etc.
　本発明の医薬品は、本発明の皮膚外用剤に加えて、薬学的に許容される担体又は添加剤を含有していてもよい。本発明の医薬品において、担体又は添加剤の配合割合は、医薬品分野において通常採用されている範囲に基づいて適宜設定すればよい。配合できる担体又は添加剤は特に制限されず、例えば、水、生理食塩水、その他の水性溶媒、水性又は油性基剤等の各種担体、賦形剤、結合剤、ｐＨ調整剤、崩壊剤、吸収促進剤、滑沢剤、着色剤、香料等の各種添加剤等が挙げられるがこれらに限定されない。 The pharmaceutical product of the present invention may contain a pharmaceutically acceptable carrier or additive in addition to the skin external preparation of the present invention. In the pharmaceutical of the present invention, the blending ratio of carriers or additives may be appropriately set based on the range normally employed in the pharmaceutical field. The carriers or additives that can be incorporated are not particularly limited, and include various carriers such as water, physiological saline, other aqueous solvents, aqueous or oily bases, excipients, binders, pH adjusters, disintegrants, and absorbents. Examples include, but are not limited to, various additives such as accelerators, lubricants, colorants, and fragrances.
　本発明の医薬品は、本発明の効果を損なわない範囲で、その他の有効成分をさらに含んでいてもよい。有効成分の具体例として、例えば、抗酸化成分、老化防止成分、抗炎症成分、抗たるみ成分、美白成分、細胞賦活化成分、血行促進成分、保湿成分、ＤＮＡの損傷の予防および／または修復作用を有する成分、抗糖化成分、ペプチドまたはその誘導体、アミノ酸またはその誘導体等が挙げられるがこれらに限定されない。 The pharmaceutical product of the present invention may further contain other active ingredients to the extent that the effects of the present invention are not impaired. Specific examples of active ingredients include antioxidant ingredients, anti-aging ingredients, anti-inflammatory ingredients, anti-sagging ingredients, whitening ingredients, cell activation ingredients, blood circulation promoting ingredients, moisturizing ingredients, and DNA damage prevention and/or repair effects. , anti-glycation components, peptides or derivatives thereof, amino acids or derivatives thereof, etc., but are not limited to these.
　出願人は、本発明の皮膚外用剤を塗布することにより、塗布部位において皮膚メラニン量の減少効果が得られることを確認している。したがって、本発明の皮膚外用剤は皮膚メラニン量の減少剤と称することができる。 The applicant has confirmed that by applying the skin external preparation of the present invention, the effect of reducing the amount of skin melanin can be obtained at the application site. Therefore, the skin external preparation of the present invention can be referred to as an agent for reducing the amount of skin melanin.
　出願人は、本発明の皮膚外用剤を塗布することにより、塗布部位において皮膚弾力の改善作用が得られることを確認している。したがって、本発明の皮膚外用剤は皮膚弾力の改善剤と称することができる。 The applicant has confirmed that by applying the external skin preparation of the present invention, an effect of improving skin elasticity can be obtained at the application site. Therefore, the skin external preparation of the present invention can be referred to as a skin elasticity improving agent.
　出願人は、本発明の皮膚外用剤を塗布することにより、塗布部位において皮膚透明感の改善作用が得られることを確認している。したがって、本発明の皮膚外用剤は皮膚透明感の改善剤と称することができる。 The applicant has confirmed that by applying the external skin preparation of the present invention, an effect of improving skin transparency can be obtained at the application site. Therefore, the skin external preparation of the present invention can be referred to as an agent for improving skin transparency.
　本発明の皮膚外用剤に含まれる米糠油不ケン化物濃縮物の含有量は、塗布により皮膚メラニン量の減少および／または皮膚弾力の増加および／または皮膚透明感の改善の作用が得られる程度に含まれていればよく、特に限定されない。例えば、本発明の皮膚外用剤全体に対して、０．０１質量％以上、０．１質量％以上、１質量％以上、１０質量％以上であってもよい。本発明の皮膚外用剤に含まれる米糠油不ケン化物濃縮物の含有量の上限としては、特に限定されず、例えば、１００質量％以下、９５質量％以下、９０質量％以下、８０質量％以下、７０質量％以下であってもよい。 The content of the rice bran oil unsaponifiables concentrate contained in the skin external preparation of the present invention is set to such an extent that upon application, the effects of reducing the amount of skin melanin, increasing skin elasticity, and/or improving skin transparency can be obtained. There is no particular limitation as long as it is included. For example, it may be 0.01% by mass or more, 0.1% by mass or more, 1% by mass or more, or 10% by mass or more with respect to the entire skin external preparation of the present invention. The upper limit of the content of rice bran oil unsaponifiables concentrate contained in the skin external preparation of the present invention is not particularly limited, and for example, 100% by mass or less, 95% by mass or less, 90% by mass or less, 80% by mass or less , 70% by mass or less.
　本発明で用いる米糠油不ケン化物濃縮物は、一般的な米油に含有される成分である、γ－オリザノール、フェルラ酸、ワックス、グルコシドセラミド等を含有している。したがって、本発明の皮膚外用剤は、米糠油不ケン化物濃縮物に含有される成分と、米油に含有される他の成分との相乗効果により、皮膚メラニン量の減少および／または皮膚弾力の増加および／または皮膚透明感の改善という優れた効果を奏していると考えられる。 The rice bran oil unsaponifiables concentrate used in the present invention contains γ-oryzanol, ferulic acid, wax, glucoside ceramide, etc., which are components contained in common rice bran oil. Therefore, the skin external preparation of the present invention reduces the amount of skin melanin and/or improves skin elasticity due to the synergistic effect of the ingredients contained in the rice bran oil unsaponifiables concentrate and other ingredients contained in the rice bran oil. It is thought that this has an excellent effect of increasing skin transparency and/or improving skin transparency.
　本発明の皮膚外用剤が適用される動物は、特に限定されず、例えばヒトまたはヒト以外の動物等であってもよい。本発明の皮膚外用剤が効果を発揮する動物の部位としては、特に限定されず、例えば、顔（額、頬等）、腕、足等の肌等が挙げられる。 The animal to which the skin external preparation of the present invention is applied is not particularly limited, and may be, for example, a human or a non-human animal. The parts of animals on which the external skin preparation of the present invention is effective are not particularly limited, and include, for example, the skin of the face (forehead, cheeks, etc.), arms, legs, etc.
　本発明の皮膚外用剤の使用頻度としては、特に限定されず、例えば、１日１回以上、１日１～３回の範囲内等が挙げられる。 The frequency of use of the skin external preparation of the present invention is not particularly limited, and includes, for example, once or more a day, 1 to 3 times a day, etc.
　本発明の皮膚外用剤の使用期間としては、特に限定されず、例えば、１週間以上、２週間以上、４週間以上であってもよい。 The period of use of the skin external preparation of the present invention is not particularly limited, and may be, for example, one week or more, two weeks or more, or four weeks or more.
　本発明の皮膚外用剤の１日の使用量としては、特に限定されず、例えば、米糠油不ケン化物濃縮物換算量で１ｍｇ以上、１０ｍｇ以上、１００ｍｇ以上等であってもよい。１日の使用目安量の上限としては、特に限定されず、例えば、米糠油不ケン化物濃縮物換算量で１０００ｍｇであってもよい。 The daily usage amount of the skin external preparation of the present invention is not particularly limited, and may be, for example, 1 mg or more, 10 mg or more, 100 mg or more in terms of rice bran oil unsaponifiables concentrate. The upper limit of the recommended daily usage amount is not particularly limited, and may be, for example, 1000 mg in terms of rice bran oil unsaponifiables concentrate.
　以下、実施例により本発明を詳細に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited thereto.
〔試験例１：半顔塗布による皮膚の改善効果〕
　下記表１に示す試薬を混合し、実施例１および比較例１のクリームを調製した。実施例及び比較例においては、米糠油不ケン化物濃縮物（商品名：ライストリエノール、築野食品工業株式会社製）または同量の精製水を用いた。 [Test Example 1: Skin improvement effect by applying on half the face]
Creams of Example 1 and Comparative Example 1 were prepared by mixing the reagents shown in Table 1 below. In the Examples and Comparative Examples, rice bran oil unsaponifiables concentrate (trade name: Rice Trienol, manufactured by Tsukino Foods Co., Ltd.) or the same amount of purified water was used.
　表１に各試験用クリーム１００ｇあたりの組成を示す。
Table 1 shows the composition per 100 g of each test cream.
１．　試験用クリームの調製
　実施例１および比較例１の各クリームは、以下の手順に従って調製した。
（１）精製水にグリセリンを添加し、８０℃のウォーターバス（TBM204AA、株式会社アドバンテック社製）で加温して溶解した。
（２）ＢＧにメチルパラベンを添加し、８０℃のウォーターバスで加温して溶解した。
（３）（２）を（１）に添加し、均一になるまで撹拌した（Ａ）。
（４）コメヌカエキス（米糠油不ケン化物濃縮物）、トリエチルヘキサノイン、ジメチコン、ステアリン酸グリセリル、ステアリン酸グリセリル（ＳＥ）、ポリソルベート２０、セテアリルアルコール、ベヘニルアルコールをそれぞれ計量の後、添加して均一になるまで撹拌した（Ｂ）。
（５）Ａのビーカーをウォーターバスに移し、ホモジナイザー（商品名：T.K.ロボミックス、プライミクス株式会社製）で攪拌しながらＢを加えて乳化した（約３５００ｒｐｍ、５分）。
（６）攪拌後、速やかに冷やしながら混ぜて３０℃以下まで冷まし、１０％クエン酸水溶液でｐＨを５．５付近に調整した。
（７）クリームに混入した空気を除去するために、真空ポンプ（GLD-040、アルバック機工株式会社製）を用いて脱気した。 1. Preparation of test creams Each cream of Example 1 and Comparative Example 1 was prepared according to the following procedure.
(1) Glycerin was added to purified water and dissolved by heating in an 80°C water bath (TBM204AA, manufactured by Advantech Co., Ltd.).
(2) Methylparaben was added to BG and dissolved by heating in a water bath at 80°C.
(3) (2) was added to (1) and stirred until homogeneous (A).
(4) After weighing rice bran extract (rice bran oil unsaponifiables concentrate), triethylhexanoin, dimethicone, glyceryl stearate, glyceryl stearate (SE), polysorbate 20, cetearyl alcohol, and behenyl alcohol, add them uniformly. (B).
(5) The beaker of A was transferred to a water bath, and while stirring with a homogenizer (trade name: TK Robomix, manufactured by Primix Co., Ltd.), B was added and emulsified (approximately 3500 rpm, 5 minutes).
(6) After stirring, the mixture was quickly cooled to below 30° C., and the pH was adjusted to around 5.5 with a 10% aqueous citric acid solution.
(7) In order to remove air mixed in the cream, it was degassed using a vacuum pump (GLD-040, manufactured by ULVAC Kiko Co., Ltd.).
２．　材料
　上記試験用クリームに用いた試薬は以下の通りである。
・精製水（製造元：オルガノ株式会社）
・ＢＧ（商品名：1,3－ブチレングリコール、製造元：株式会社ダイセル）
・メチルパラベン（商品名：NIPAGIN M、製造元：クラリアントジャパン株式会社）
・グリセリン（商品名：化粧品用濃グリセリン、製造元：花王株式会社）
・米糠油不ケン化物濃縮物（商品名：ライストリエノール（ＲＴＮ）、製造元：築野食品工業株式会社）
・トリエチルヘキサノイン（商品名：FineNeo-IOTG、製造元：日本精化株式会社）
・ジメチコン（商品名：DOWSIL SH 200 C Fluid 6cs、製造元：ダウ・ケミカル日本株式会社）
・ステアリン酸グリセリル（商品名：NIKKOL MGS-AV、製造元：日光ケミカルズ株式会社）
・ステアリン酸グリセリル（SE）（商品名：NIKKOL MGS-BSEV、製造元：日光ケミカルズ株式会社）
・ポリソルベート20（商品名：レオドールスーパーTW-L120、製造元：花王株式会社）
・セテアリルアルコール（商品名：Lanette O、製造元：BASFジャパン株式会社）
・ベヘニルアルコール（商品名：Lanette 22NF、製造元：BASFジャパン株式会社）
・クエン酸（製造元：富士フィルム和光純薬株式会社） 2. Materials The reagents used in the above test cream are as follows.
・Purified water (manufacturer: Organo Co., Ltd.)
・BG (Product name: 1,3-butylene glycol, Manufacturer: Daicel Corporation)
・Methylparaben (Product name: NIPAGIN M, Manufacturer: Clariant Japan Co., Ltd.)
・Glycerin (Product name: Concentrated glycerin for cosmetics, Manufacturer: Kao Corporation)
・Rice bran oil unsaponifiables concentrate (Product name: Rice Trienol (RTN), Manufacturer: Tsukino Foods Co., Ltd.)
・Triethylhexanoin (Product name: FineNeo-IOTG, Manufacturer: Nippon Fine Chemical Co., Ltd.)
・Dimethicone (Product name: DOWSIL SH 200 C Fluid 6cs, Manufacturer: Dow Chemical Japan Co., Ltd.)
・Glyceryl stearate (Product name: NIKKOL MGS-AV, Manufacturer: Nikko Chemicals Co., Ltd.)
・Glyceryl stearate (SE) (Product name: NIKKOL MGS-BSEV, Manufacturer: Nikko Chemicals Co., Ltd.)
・Polysorbate 20 (Product name: Rheodor Super TW-L120, Manufacturer: Kao Corporation)
・Cetearyl alcohol (product name: Lanette O, manufacturer: BASF Japan Ltd.)
・Behenyl alcohol (product name: Lanette 22NF, manufacturer: BASF Japan Co., Ltd.)
・Citric acid (manufacturer: Fuji Film Wako Pure Chemical Industries, Ltd.)
３．　試験方法
３．１　試験概要
　以下の条件で試験を実施した。
試験方法　：プラセボ対照単盲検試験
試験参加者：女性２０代～５０代
被検者数　：２２人（うち１人は８週目以降に脱落）
試料　　　：１％ＲＴＮ配合クリーム（ＲＴＮ　１ｇ／１００ｇ）（実施例１、表１参照）またはプラセボクリーム（精製水　１ｇ／１００ｇ）（比較例１、表１参照）
使用方法　：１日２回、約０．４ｇ／回の１％ＲＴＮ配合クリームを右半顔に塗布し、同時に同量のプラセボクリームを左半顔に塗布する
試験期間　：３ヶ月
検査回数　：４回（試験開始前（０週目）、試験中（４週目、８週目、１２週目）） 3. Test method 3.1 Test overview The test was conducted under the following conditions.
Test method: Placebo-controlled, single-blind test Participants: Females in their 20s to 50s Number of subjects: 22 (one of them dropped out after 8 weeks)
Sample: 1% RTN combination cream (RTN 1g/100g) (see Example 1, Table 1) or placebo cream (purified water 1g/100g) (Comparative Example 1, see Table 1)
How to use: Apply approximately 0.4 g/time of 1% RTN cream to the right half of the face twice a day, and at the same time apply the same amount of placebo cream to the left half of the face Test period: 3 months Number of tests: 4 times (before the start of the test (0th week), during the test (4th week, 8th week, 12th week))
３．２　評価方法
　皮膚データの取得を以下の方法で実施した。 3.2 Evaluation method Skin data was acquired using the following method.
３．２．１　肌の順化
　被検者は、クレンジングオイル（商品名：カウブランド無添加メイク落としオイル、牛乳石鹸共進社製）でメイクを落とし、洗顔料（商品名：カウブランド無添加泡の洗顔料、牛乳石鹸共進社製）で皮膚上の皮脂や汚れを落としたうえで、乾いたタオルで水分を拭き取り、恒温恒湿室（温度２２℃、湿度５０％）に入室した。入室後２０分間待機し、肌を順化した。 3.2.1 Skin acclimatization Subjects removed their makeup with cleansing oil (product name: Cow Brand Additive-free Makeup Remover Oil, manufactured by Milk Soap Kyoshinsha), and then applied face wash (product name: Cow Brand Additive-free Foam). After removing sebum and dirt from the skin with a facial cleanser (Milk Soap (manufactured by Kyoshinsha)), the participants wiped off moisture with a dry towel and entered a constant temperature and humidity room (temperature 22°C, humidity 50%). After entering the room, I waited for 20 minutes to allow my skin to acclimatize.
３．２．２　メラニン量
　マルチ皮膚測定器（Courage＋Khazaka社製）に接続したメラニン・紅斑ヘモグロビン測定プローブ（Mexameter MX18、Courage＋Khazaka社製）を頬骨の皮膚に接触させ、メラニン量を測定した。被検者一人につき左右各３回測定し、平均値を被検者ごとの値とした。統計処理には、Dunnet's testおよびStudent's t－testを使用した。 3.2.2 Amount of Melanin A melanin/erythema hemoglobin measurement probe (Mexameter MX18, manufactured by Courage + Khazaka) connected to a multi-dermatometer (manufactured by Courage + Khazaka) was brought into contact with the skin of the cheekbone, and the amount of melanin was measured. Each subject was measured three times on each side, and the average value was taken as the value for each subject. Dunnet's test and Student's t-test were used for statistical processing.
３．２．３　透明感およびキメの体感
　被検者が恒温恒湿室で２０分間待機し、肌を順化している間に視覚的アナログスケール（VAS、Visual Analogue Scale）アンケートの記入を実施した。長さ１０ｃｍの線（左端が「非常に悪い」、右端が「非常に良い」）を被験者に見せ、検査時の顔の透明感およびキメの体感がどの程度かを線上に図示してもらった。各検査日での「非常に悪い」からの距離の平均を算出した。統計処理にはDunnet's testおよびStudent's t－testを使用した。 3.2.3 Transparency and Texture Experience Subjects waited in a constant temperature and humidity room for 20 minutes, and while their skin was acclimating, they filled out a Visual Analogue Scale (VAS) questionnaire. . A 10 cm long line (the left end was "very bad" and the right end was "very good") was shown to the subjects, and they were asked to indicate on the line how much they felt about the clarity and texture of their face during the test. . The average distance from "very poor" for each test date was calculated. Dunnet's test and Student's t-test were used for statistical processing.
３．２．４　正味粘弾性
　皮膚粘弾性測定装置（Cutometer Dual MPA 580、Courage＋Khazaka社製）の粘弾性プローブ（Cutometer CT 580 MP、プローブ径６ｍｍ、Courage＋Khazaka社製）を頬骨の皮膚に接触させ、陰圧（450mbar、吸引時間３秒、弛緩時間３秒）をかけて正味粘弾性を測定した。被検者一人につき左右各３回測定し、平均値を被検者ごとの値とした。統計処理にはStudent's t－testを使用した。 3.2.4 Net viscoelasticity The viscoelastic probe (Cutometer CT 580 MP, probe diameter 6 mm, manufactured by Courage + Khazaka) of the skin viscoelasticity measuring device (Cutometer Dual MPA 580, manufactured by Courage + Khazaka) was brought into contact with the skin of the cheekbone, and The net viscoelasticity was measured by applying pressure (450 mbar, suction time 3 seconds, relaxation time 3 seconds). Each subject was measured three times on each side, and the average value was taken as the value for each subject. Student's t-test was used for statistical processing.
３．２．５　弾力の体感
　被検者が恒温恒湿室で２０分間待機し、肌を順化している間にVASアンケートの記入を実施した。長さ１０ｃｍの線（左端が「非常に悪い」、右端が「非常に良い」）を被験者に見せ、検査時の肌の弾力の体感がどの程度かを線上に図示してもらった。各検査日での「非常に悪い」からの距離の平均を算出した。統計処理にはDunnet's testおよびStudent's t－testを使用した。 3.2.5 Feeling of elasticity The subjects waited in a constant temperature and humidity room for 20 minutes, and while their skin was acclimatizing, they filled out the VAS questionnaire. The test subjects were shown a 10 cm long line (the left end being ``very poor'' and the right end being ``very good''), and asked to indicate on the line how much they felt about their skin's elasticity at the time of the test. The average distance from "very poor" for each test date was calculated. Dunnet's test and Student's t-test were used for statistical processing.
４．結果
４．１　メラニン量
　図１は、試験開始前のメラニン量を０とした場合のメラニン量の変化量を示した図である。試験開始直後、ＲＴＮ群（四角）およびプラセボ群（丸）ともにメラニン量の減少が認められた。プラセボ群では８週目から１２週目にかけてメラニン量の変化が増加に転じたのに対し、ＲＴＮ群では試験開始から１２週目まで継続して有意に減少していた。群間での有意差は１２週目において認められた（ｐ＜０．０１）。 4. Results 4.1 Amount of Melanin FIG. 1 is a diagram showing the amount of change in the amount of melanin when the amount of melanin before the start of the test is set to 0. Immediately after the start of the study, a decrease in the amount of melanin was observed in both the RTN group (squares) and the placebo group (circles). In the placebo group, the change in melanin amount started to increase from week 8 to week 12, whereas in the RTN group, it continued to significantly decrease from the start of the study until week 12. A significant difference between groups was observed at week 12 (p<0.01).
４．２　透明感およびキメの体感
　図２は、試験開始前の透明感（図２Ａ）およびキメ（図２Ｂ）の体感の程度を０とした場合の変化量を示した図である。ＲＴＮ群（四角）では４週目から８週目にかけて、試験開始前と比べて体感される透明感に有意な改善が認められた。キメについても、ＲＴＮ群では試験開始から４週目にかけて試験開始前と比べた体感に大幅な改善が認められ、改善された状態は１２週目まで維持されていた。一方、プラセボ群（丸）ではこのような体感の改善は確認されなかった。 4.2 Transparency and texture sensation FIG. 2 is a diagram showing the amount of change when the degree of transparency (FIG. 2A) and texture (FIG. 2B) before the start of the test is set to 0. In the RTN group (squares), from the 4th week to the 8th week, a significant improvement in perceived clarity was observed compared to before the start of the test. Regarding texture, in the RTN group, there was a significant improvement in physical sensation compared to before the start of the test during the fourth week after the start of the test, and the improved state was maintained until the 12th week. On the other hand, no such improvement in physical sensation was observed in the placebo group (circle).
４．３　正味粘弾性
　図３は、試験開始前の正味粘弾性（Ｒ５）を０とした場合の正味粘弾性の変化量を示した図である。ＲＴＮ群（四角）では試験開始から４週目にかけて正味粘弾性が増加し、その後１２週目にかけて緩やかな増加の維持が認められた。 4.3 Net Viscoelasticity FIG. 3 is a diagram showing the amount of change in net viscoelasticity when the net viscoelasticity (R5) before the start of the test is set to 0. In the RTN group (squares), the net viscoelasticity increased from the start of the test to the 4th week, and then maintained a gradual increase until the 12th week.
４．４　弾力の体感
　図４は、試験開始前の弾力の体感の程度を０とした場合の変化量を示した図である。ＲＴＮ群（四角）では試験開始から４週目にかけて、試験開始前と比べて体感される弾力に大幅な改善が認められプラセボ群と比べて有意な改善が認められた。さらに、改善された状態は１２週目まで維持されていた。 4.4 Physical sensation of elasticity FIG. 4 is a diagram showing the amount of change when the level of elasticity sensation before the start of the test is set to 0. In the RTN group (squares), from the start of the study to the fourth week, a significant improvement was observed in the perceived elasticity compared to before the start of the study, and a significant improvement was observed compared to the placebo group. Furthermore, the improved condition was maintained until the 12th week.
　なお本発明は上述した各実施形態および実施例に限定されるものではなく、請求項に示した範囲で種々の変更が可能であり、異なる実施形態にそれぞれ開示された技術的手段を適宜組み合わせて得られる実施形態についても本発明の技術的範囲に含まれる。また、本明細書中に記載された学術文献および特許文献の全てが、本明細書中において参考として援用される。 It should be noted that the present invention is not limited to the embodiments and examples described above, and various changes can be made within the scope of the claims, and technical means disclosed in different embodiments can be combined as appropriate. The resulting embodiments also fall within the technical scope of the present invention. Additionally, all academic and patent documents mentioned herein are incorporated by reference herein.

Claims (9)

  1. 　米糠油不ケン化物濃縮物を含有する皮膚外用剤。 A topical skin preparation containing rice bran oil unsaponifiables concentrate.
  2. 　米糠油不ケン化物濃縮物が、植物ステロール、トコフェロール、トコトリエノールおよびスクワレンを含む、請求項１に記載の皮膚外用剤。 The skin external preparation according to claim 1, wherein the rice bran oil unsaponifiables concentrate contains plant sterols, tocopherols, tocotrienols, and squalene.
  3. 　皮膚メラニン量の減少および皮膚弾力の増加の作用を有する、請求項１に記載の皮膚外用剤。 The skin external preparation according to claim 1, which has the effect of reducing the amount of skin melanin and increasing skin elasticity.
  4. 　さらに皮膚透明感の改善の作用を有する、請求項３に記載の皮膚外用剤。 The skin external preparation according to claim 3, which further has the effect of improving skin transparency.
  5. 　請求項１～４のいずれか一項に記載の皮膚外用剤を含むことを特徴とする化粧品。 A cosmetic product comprising the skin external preparation according to any one of claims 1 to 4.
  6. 　請求項１～４のいずれか一項に記載の皮膚外用剤を含むことを特徴とする医薬品。 A pharmaceutical product comprising the skin external preparation according to any one of claims 1 to 4.
  7. 　米糠油不ケン化物濃縮物を含有する皮膚メラニン量の減少剤。 A skin melanin amount reducing agent containing rice bran oil unsaponifiables concentrate.
  8. 　米糠油不ケン化物濃縮物を含有する皮膚弾力の改善剤。 A skin elasticity improving agent containing rice bran oil unsaponifiables concentrate.
  9. 　米糠油不ケン化物濃縮物を含有する皮膚透明感の改善剤。 A skin transparency improver containing rice bran oil unsaponifiables concentrate.
PCT/JP2023/020270 2022-06-01 2023-05-31 External skin preparation containing unsaponified concentrate of rice bran oil WO2023234345A1 (en)

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Citations (6)

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Publication number Priority date Publication date Assignee Title
JPH11269024A (en) * 1998-03-18 1999-10-05 Pola Chem Ind Inc P-related gene expression inhibitor and cosmetic containing the same
JP2002255784A (en) * 2001-03-02 2002-09-11 Oriza Yuka Kk Composition for beautiful skin
JP2005255746A (en) * 2004-03-10 2005-09-22 Chikuno Shokuhin Kogyo Kk Method for producing concentrate of rice bran oil deodorized scum unsaponifiables
JP2013060418A (en) * 2011-08-24 2013-04-04 Niigata Univ Tyrosinase activity inhibitory agent
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Publication number Priority date Publication date Assignee Title
JPH11269024A (en) * 1998-03-18 1999-10-05 Pola Chem Ind Inc P-related gene expression inhibitor and cosmetic containing the same
JP2002255784A (en) * 2001-03-02 2002-09-11 Oriza Yuka Kk Composition for beautiful skin
JP2005255746A (en) * 2004-03-10 2005-09-22 Chikuno Shokuhin Kogyo Kk Method for producing concentrate of rice bran oil deodorized scum unsaponifiables
JP2013060418A (en) * 2011-08-24 2013-04-04 Niigata Univ Tyrosinase activity inhibitory agent
JP2020180072A (en) * 2019-04-25 2020-11-05 サンスター株式会社 Anti-skin photoaging composition for external use
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