Method for reducing skin irritation caused by oil-soluble active ingredients, and method for controlling percutaneous penetration rate of oil-soluble active ingredients

Abstract

To provide a method for reducing skin irritation caused by oil-soluble active ingredients, and to provide a method for controlling percutaneous penetration rate.SOLUTION: Provided is a method for alleviating the skin irritation of an oil-soluble active ingredient (A) contained in a composition for external use on the skin by using an oil agent (B), or a method for controlling the percutaneous penetration rate of an oil-soluble active ingredient (A) by using an oil agent (B); the difference (|IOBA-IOBB|) between the IOB value (IOBA) of the oil-soluble active ingredient (A) and the IOB value (IOBB) of the oil agent (B) being set to a range of 0.00 to 0.25, and the oil agent (B) being incorporated in an amount of 10 mass% or more relative to the total amount of the composition for external use on the skin.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for reducing the skin irritation of an oil-soluble active ingredient, a method for controlling the transdermal penetration rate, and the like. [Background technology]

[0002] Various active ingredients are blended in skin external compositions to provide cosmetic effects to the skin, etc. In recent years, for example, cosmetics blended with retinol and its derivatives as ingredients having wrinkle improving effects have been attracting attention.

[0003] However, oil-soluble active ingredients such as retinol tend to easily penetrate the skin due to their affinity for the skin, etc. Therefore, for example, in a skin topical composition containing an oil-soluble active ingredient such as retinol, a predetermined amount of the oil-soluble active ingredient quickly penetrates the skin, which may result in skin irritation, etc. This is a particular concern for sensitive skin or dry skin.

[0004] Conventionally, some techniques have been proposed to mitigate skin irritation by controlling the penetration speed of oil-soluble active ingredients.For example, a method has been proposed in which a nonionic surfactant and, if desired, a polyhydric alcohol are dissolved in ion-exchanged water, heated to 85-95°C, wax is added so that the mass ratio of nonionic surfactant / wax is 1.0 or more, propeller stirring is performed for about 30 minutes to 2 hours, an oil-soluble drug is added thereto, and then ice-cooling is performed to obtain an oil-soluble drug-containing wax fine dispersion composition (see Patent Document 1).However, in the actual manufacturing process, it is difficult to appropriately control the ice-cooling process, and there are relatively large restrictions on formulation design and manufacturing method, making it unsuitable for industrialization. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2009-155326 A Summary of the Invention [Problem to be solved by the invention]

[0006] The reality is that there is still room for improvement in the methods for reducing skin irritation that have been proposed so far, and new methods that differ from the conventional methods are required.

[0007] The present invention has been made in consideration of the above circumstances, and aims to provide a new method for reducing the skin irritation of an oil-soluble active ingredient, and a new method for controlling the transdermal permeation rate of an oil-soluble active ingredient. [Means for solving the problem]

[0008] In view of the above circumstances, the present inventors, in the process of intensively studying a method for reducing the skin irritation of an oil-soluble active ingredient and / or controlling the percutaneous penetration rate, focused on the technical relationship between the percutaneous penetration rate or skin irritation of the oil-soluble active ingredient and the characteristics of the oil agent co-blended with it. As a result of further intensive research from this point of view, the present inventors unexpectedly found that the difference between the IOB value of the oil-soluble active ingredient and the IOB value of the oil agent (|IOB A -IOB B The present inventors have found that by setting the amount of the oil agent in the range of 0.1 to 1.0 μg / ml and further setting the amount of the oil agent in the range of 0.1 to 1.0 μg / ml, the skin irritation of the oil-soluble active ingredient can be alleviated and the percutaneous penetration rate can be controlled, thereby completing the present invention.

[0009] That is, the present invention provides the following [1] to [8]. [1] A method for reducing the skin irritation of an oil-soluble active ingredient (A) contained in a composition for external use on the skin by using an oil agent (B), comprising: A ) and the IOB value of the (B) oil (IOB B ) and (|IOB A -IOB B |) in the range of 0.00 to 0.25, and the (B) oil agent is blended in an amount of 10 mass% or more based on the total amount of the topical skin composition, thereby reducing the skin irritation caused by the (A) oil-soluble active ingredient. [2] A method for controlling the percutaneous penetration rate of an oil-soluble active ingredient (A) incorporated in a composition for external use on the skin by using an oil agent (B), comprising: A ) and the IOB value of the (B) oil (IOB B ) and (|IOB A -IOB B |) in the range of 0.00 to 0.25, and the (B) oil agent is blended in an amount of 10 mass% or more based on the total amount of the topical skin composition, thereby controlling the transdermal penetration rate of the (A) oil-soluble active ingredient. [3] The method according to [1] or [2], wherein the oil-soluble active ingredient (A) is one or more selected from the group consisting of retinol and its derivatives. [4] The method according to [3], wherein the amount of one or more selected from the group consisting of retinol and its derivatives is 0.03% by mass or more relative to the total amount of the topical skin composition. [5] The IOB value of the (B) oil solution (IOB B ) is 0.07 to 0.32. [6] The method according to any of [1] to [5], wherein the (B) oil agent is at least one selected from the group consisting of vegetable oils and sterol ester oils. [7] The method according to any one of [1] to [6], wherein the composition for external application to the skin is an oil-in-water type composition for external application to the skin. [8] A skin irritation mitigating agent used for mitigating the skin irritation of an (A) oil-soluble active ingredient, the skin irritation mitigating agent comprising a (B) oil agent having an IOB value that differs from the IOB value of the (A) oil-soluble active ingredient by 0.00 to 0.25. Effect of the Invention

[0010] According to the present invention, it is possible to provide a new method for reducing the skin irritation caused by an oil-soluble active ingredient, and a new method for controlling the transdermal penetration rate of an oil-soluble active ingredient. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] An embodiment of the present invention will be described in detail below, however, the present invention is not limited to the following embodiment.

[0012] The term "IOB value" in this specification is an abbreviation for Inorganic / Organic Balance, which is a value corresponding to the ratio of the inorganic value of a compound to the organic value of the compound determined by an organic conceptual diagram, and is a value indicating the degree of polarity of an organic compound (e.g., Fujita Atsushi, Prediction of Organic Compounds and Organic Conceptual Diagrams, Chemistry Region Vol. 11, No. 10 (1957) pp. 719-725).

[0013] In this specification, "oil-soluble" means water-insoluble, and specifically means that the solubility in water at 20°C is 0.1 g / 100 ml or less.

[0014] In this specification, the term "composition for external use on the skin" refers to a composition that is applied to the outer skin (including the scalp), such as a cosmetic preparation that is applied to the outer skin.

[0015] In addition, in this specification, "sensitive skin" refers to skin in a state where abnormalities occur in the stratum corneum, the structure of the stratum corneum is disturbed, and the skin reacts sensitively to physical and / or chemical stimuli (sunlight, air pollution, active oxygen, chemicals, temperature, dryness, smoking, excessive skin washing, stress, etc.) In addition, "dry skin" refers to skin in a dry state where the moisturizing function is reduced.

[0016] In this specification, "X and / or Y (X and Y are optional configurations)" means at least one of X and Y, and means the following three cases: X only, Y only, and X and Y.

[0017] The present invention relates to a method for reducing the skin irritation of an oil-soluble active ingredient (A) (hereinafter, may be referred to as "component (A)") incorporated in a composition for topical skin application by using an oil (B) (hereinafter, may be referred to as "component (B)"), and / or a method for controlling the transdermal penetration rate of component (A) incorporated in a composition for topical skin by using component (B).

[0018] <Methods to mitigate skin irritation caused by oil-soluble active ingredients> A method for reducing the skin irritation caused by an oil-soluble active ingredient according to one embodiment of the present invention (hereinafter, sometimes referred to as the present irritation reduction method) is a method for reducing the skin irritation caused by an oil-soluble active ingredient (A) contained in a composition for external use on the skin by using an oil agent (B), and the IOB value (IOB A ) and the IOB value of the (B) oil (IOB B ) and (|IOB A -IOB B |) is in the range of 0.00 to 0.25, and the (B) oil agent is blended in an amount of 10 mass % or more relative to the total amount (100 mass %) of the composition for external use on skin. The present invention relates to a method for reducing skin irritation, which comprises blending or allowing a specific oil (B) to coexist with an oil-soluble active ingredient (A), and is capable of reducing the skin irritation of the oil-soluble active ingredient (A). The present inventors were the first to discover that the present method can reduce and / or soothe irritation caused by the oil-soluble active ingredient, and can provide a new method for reducing skin irritation that is different from conventional methods. Although the mechanism by which the present irritation alleviation method can alleviate irritation caused by oil-soluble active ingredients on the skin is not entirely clear, the present inventors believe that the method can be used to alleviate irritation caused by oil-soluble active ingredients on the skin. A -IOB B It is believed that when | is within a specific range, the rate at which oil-soluble active ingredients migrate from the formulation to the skin can be slowed down, thereby mitigating skin irritation.

[0019] According to this method for reducing irritation, for example, it is possible to increase the degree of freedom in the formulation design of a composition for external use on the skin that contains an oil-soluble active ingredient. In this method for reducing irritation, the skin irritation of component (A) can be reduced by selecting an oil (B) having a specific IOB value from among oils commonly used in this technical field based on the IOB value of component (A), which is useful in that there are relatively few restrictions on the formulation design and manufacturing method.

[0020] For example, as mentioned above, a method proposed for reducing the skin irritation of oil-soluble drugs is to dissolve a nonionic surfactant or a polyhydric alcohol in ion-exchanged water, heat the mixture to 85 to 95°C, add wax in a nonionic surfactant / wax mass ratio of 1.0 or more, stir with a propeller for about 30 minutes to 2 hours, confirm the state of solubilization, add the oil-soluble drug, and then ice-cool to obtain an oil-soluble drug-containing wax fine dispersion composition (Patent Document 1). However, it is practically difficult to appropriately control the ice-cooling process in industrialization, and the degree of freedom in formulation design is not high.

[0021] This method for reducing irritation is highly useful because it can provide a composition for external use on the skin that exerts its efficacy while reducing the skin irritation of the oil-soluble active ingredient (A) by a method with relatively few restrictions on formulation design and manufacturing method. For example, when retinol or the like, which is one of the oil-soluble active ingredients (A) that is likely to cause skin irritation, is used in this method for reducing irritation, it can provide a composition for external use on the skin that exerts its excellent efficacy (e.g., wrinkle improvement effect) while reducing the skin irritation of retinol or the like, and is therefore particularly useful.

[0022] Furthermore, since sensitive skin and dry skin tend to be more sensitive to skin irritants such as retinol, one embodiment of this method for reducing irritation is extremely useful as a method for reducing the skin irritation of component (A) contained in a topical skin composition for sensitive skin and / or dry skin by using component (B).

[0023] In this irritation reduction method, the IOB value of component (A) (IOB A) and (B) the IOB value of the component (IOB B ) and (|IOB A -IOB B It is important that the difference (|IOB A -IOB B |) is preferably from 0.00 to 0.20, more preferably from 0.00 to 0.10, and even more preferably from 0.00 to 0.05. Specifically, for example, when retinol (IOB value: 0.32) is used as component (A), the skin irritation of retinol can be mitigated by using an oil agent (B) with an IOB value within the range of 0.07 to 0.32.

[0024] <Method for controlling the transdermal penetration rate of oil-soluble active ingredients> A method for controlling the percutaneous penetration rate of an oil-soluble active ingredient according to one embodiment of the present invention (hereinafter, sometimes referred to as the "percutaneous penetration rate control method") is a method for controlling the percutaneous penetration rate of component (A) contained in a composition for external use on skin by using component (B), the method comprising the steps of: A ) and the IOB value of the (B) component (IOB B ) and (|IOB A -IOB B |) is in the range of 0.00 to 0.25, and the component (B) is blended in an amount of 10% by mass or more relative to the total amount (100% by mass) of the composition for external use on skin. According to the present invention, the percutaneous permeation rate of the oil-soluble active ingredient (A) can be controlled by mixing or coexisting the component (B) with the component (A). The present inventors were the first to discover that the percutaneous permeation amount of the oil-soluble active ingredient within a given time period can be suppressed and / or reduced by the present invention, and a new method for controlling the percutaneous permeation rate different from conventional methods can be provided.

[0025] According to this permeation rate control method, for example, the degree of freedom in the formulation design of a skin topical composition containing an oil-soluble active ingredient can be increased. In this permeation rate control method, the percutaneous permeation rate of the (A) component can be suppressed by selecting an oil (B) having a specific IOB value from among oils commonly used in this technical field based on the IOB value of the (A) component, which is useful in that there are relatively few restrictions on the formulation design and manufacturing method. In addition, according to this permeation rate control method, for example, it is expected that the (A) component can be permeated into the skin in a sustained release manner, which is also useful in terms of increasing the durability of efficacy.

[0026] This method for controlling the permeation rate is highly useful because it can provide a composition for external use on the skin that exerts its efficacy while suppressing the percutaneous permeation rate of the (A) oil-soluble active ingredient by a method with relatively few restrictions on the formulation design and manufacturing method. In the case of using retinol or the like, which is one of the (A) oil-soluble active ingredients that is of great concern for skin irritation, this method for controlling the permeation rate can suppress the percutaneous permeation rate of retinol or the like while allowing it to penetrate in a sustained manner, thereby reducing skin irritation and providing a composition for external use on the skin that exerts its efficacy sustainably, and is particularly useful.

[0027] In this method for controlling the permeation rate, the IOB value of component (A) (IOB A ) and (B) the IOB value of the component (IOB B ) and (|IOB A -IOB B It is important that |) is in the range of 0.00 to 0.25, and from the viewpoint of effectively controlling the transdermal permeation rate of the (A) component, it is preferably 0.00 to 0.20, more preferably 0.00 to 0.10, and even more preferably 0.00 to 0.05. Specifically, for example, when retinol (IOB value: 0.32) is used as component (A), the transdermal penetration rate of retinol can be suppressed by using an oil (B) having an IOB value within the range of 0.07 to 0.32.

[0028] In addition, conventionally, oleosomes and the like may be used as a component that suppresses the percutaneous penetration rate of an oil-soluble active ingredient and exhibits sustained release properties, but the raw material price of this type of component is relatively high, which may be disadvantageous in terms of production costs. If the amount of the raw material is reduced in order to reduce production costs, it tends to be difficult to obtain a sufficient effect of suppressing the penetration rate, and in many cases, measures such as reducing the amount of the oil-soluble active ingredient must be taken in order to obtain the effect of suppressing the penetration rate even with a small amount. On the other hand, the method of the present invention can utilize a general-purpose oil agent, which is advantageous in terms of production costs, does not cause the above-mentioned problems, and has the advantage of easily setting the amount of the oil-soluble active ingredient to a desired range.

[0029] Next, the components (A) and (B) used in the present irritation reduction method and the present permeation rate control method will be described in more detail. Note that hereinafter, "the present irritation reduction method and / or the present permeation rate control method" may be referred to as "the present method".

[0030] [(A) Oil-soluble active ingredient] As component (A), various oil-soluble active ingredients used in compositions for external use on the skin can be appropriately blended depending on the desired action and effect. Component (A) can be used alone or in combination of two or more kinds.

[0031] Specific examples of (A) oil-soluble active ingredients include, but are not limited to, oil-soluble vitamins and derivatives thereof, such as retinol, retinol palmitate, DL-α-tocopherol acetate, tocopherol nicotinate, ascorbyl stearate, ascorbyl palmitate, ubiquinone, α-lipoic acid, and carnitine; anti-inflammatory agents, such as allantoin, glycyrrhetinic acid, and stearyl glycyrrhetinate; preservatives and disinfectants, such as isopropylmethylphenol and triclosan; and ultraviolet absorbers, such as 2-ethylhexyl paramethoxycinnamate.

[0032] Of the components (A), oil-soluble vitamins and derivatives thereof are preferred, and among these, one or more selected from the group consisting of retinol and its derivatives are preferred. Examples of retinol and its derivatives include retinol, retinol acetate, retinol propionate, retinol butyrate, retinol octylate, retinol laurate, retinol palmitate, retinol stearate, retinol myristicate, retinol oleate, retinol linoleate, retinol linoleate, retinoic acid, retinal, methyl retinoate, ethyl retinoate, retinol retinoate, tocopherol retinoate, etc. From the viewpoint of significantly exhibiting the effects of the present invention, retinol is preferred.

[0033] In the present irritation alleviation method, a skin irritant (A) component is used as the (A) component, and in the present permeation rate control method, either a skin irritant (A) component or a non-skin irritant (A) component may be used as the (A) component. The skin irritant (A) component is not limited as long as it is an oil-soluble active ingredient that irritates the skin. Whether or not a component has skin irritation can be determined based on the knowledge of a person skilled in the art, and can also be determined by a conventionally known method such as a patch test, a stinging test, or a cytotoxicity test.

[0034] In this method, the amount of component (A) to be blended can be appropriately set depending on the type of component, the types and amounts of other components, the dosage form, etc., and is not limited, but is preferably 0.03 to 1.5 mass% relative to the total amount of the topical skin composition, and may be 0.05 to 1.0 mass%, 0.07 to 0.5 mass%, etc.

[0035] For example, when component (A) is one or more selected from the group consisting of retinol and its derivatives, the blending amount thereof is, for example, preferably 0.03 mass% or more, more preferably 0.04 to 0.50 mass%, and particularly preferably 0.045 to 0.20 mass%, relative to the total amount of the topical skin composition.

[0036] Furthermore, for example, when component (A) is one or more selected from the group consisting of retinol and its derivatives, the blending amount is, for example, preferably 30,000 units / 100 g or more, more preferably 40,000 to 500,000 units / 100 g, and even more preferably 45,000 to 200,000 units / 100 g, relative to the total amount of the topical skin composition. In addition, one unit of retinol or its derivatives refers to the international unit calculated by the method described in the Vitamin A Quantitative Method in the 18th Revised Edition of the Japanese Pharmacopoeia, and is also expressed as 1 I.U.

[0037] The IOB value of the component (A) is not limited, but is, for example, 0.01 to 1.10, 0.05 to 0.7, or 0.1 to 0.35. Furthermore, from the viewpoint of achieving a remarkable effect of the present invention, the IOB value of the component (A) is preferably from 0.01 to 0.65, more preferably from 0.10 to 0.40, and most preferably from 0.30 to 0.40.

[0038] [(B) Oil] It is important to use an oil agent (B) having an IOB value whose difference from the IOB value of component (A) is within the above-mentioned specific range. Specifically, the difference from the IOB value of component (A) for which reduction in skin irritation and / or control of the percutaneous penetration rate is required (|IOB A -IOB B It is important to use an oil having an IOB value such that | is within the range of 0.00 to 0.25. The component (B) can be used alone or in combination of two or more kinds.

[0039] The IOB value of the component (B) is not particularly limited, but can be appropriately set within the range of 0.00 to 0.50, 0.05 to 0.40, 0.1 to 0.35, etc. Specifically, for example, when retinol (IOB value: 0.32) is used as the component (A), the IOB value of the oil agent (B) is 0.07 to 0.32, more preferably 0.08 to 0.32, and even more preferably 0.09 to 0.32.

[0040] The (B) component may be liquid, semi-solid, or solid at room temperature (25° C.), and examples thereof include hydrocarbon oils, ester oils, silicone oils, higher alcohols, higher fatty acids, and oils derived from animals and plants.

[0041] As the hydrocarbon oil, paraffinic hydrocarbons and olefinic hydrocarbons are used, and examples thereof include hydrogenated lanolin, squalane, ceresin, paraffin, pristane, microcrystalline wax, liquid paraffin, petrolatum, hydrogenated polyisobutene, and light liquid paraffin.

[0042] Examples of ester oils include isopropyl myristate, butyl myristate, decyl myristate, myristyl myristate, cetyl myristate, isopropyl palmitate, cetyl palmitate, ethyl stearate, butyl stearate, stearyl stearate, isocetyl stearate, hexyl laurate, ethyl oleate, ethyl linoleate, isopropyl linoleate, cetyl caprylate, decyl oleate, oleyl oleate, isodecyl oleate, cetyl octanoate, 2-octyldodecyl myristate, and dimethyl octanoate. 2-Octyldodecyl, Hexyldecyl Dimethyloctanoate, 2-Hexyldecyl Myristate, 2-Hexyldecyl Palmitate, Diisopropyl Adipate, 2-Hexyldecyl Adipate, Diethyl Sebacate, Diisopropyl Sebacate, Isocetyl Isostearate, Isostearyl Isostearate, Isononyl Isononanoate, Isotridecyl Isononanoate, Cholesteryl 12-Hydroxystearate, Cholesteryl Stearate, Cholesteryl Oleate, Cholesteryl Isostearate, Phytosteryl Isostearate, Macadamia Phytosteryl oleate, inulin stearate, ethylene glycol di-2-ethylhexylate, cetyl 2-ethylhexanoate, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, tri-2-ethylhexyl trimellitate, tritridecyl trimellitate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, tri-2-ethylhexanoic acid Glycerin, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, glyceryl tri-2-ethylhexanoate, glyceryl trimyristate, tri(caprylic / capric)glyceryl, tri(caprylic / capric / myristic / stearic)glyceryl, medium chain triglyceride, castor oil fatty acid methyl ester, di(phytosteryl / octyldodecyl) lauroyl glutamate, di(octyldodecyl / phytosteryl / behenyl) lauroyl glutamate, cetyl lactate, myristyl lactate, cyclohexane-1,Examples of suitable glyceryl triglyceride include bisethoxydiglycol 4-dicarboxylate, lanolin acetate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, dimer dilinoleate (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleyl dimer dilinoleate, dipentaerythrityl tripolyhydroxystearate, and tri(behenic acid / isostearic acid / eicosanedioic acid)glyceryl.

[0043] Examples of silicone oils include dimethylpolysiloxane (dimethicone), methylphenylpolysiloxane, methylhydrogenpolysiloxane, octamethylcyclotetrasiloxane, octamethylcyclopentasiloxane, decamethylcyclohexasiloxane, higher alkoxy-modified silicones such as stearoxysilicone, alkyl-modified silicones, and higher fatty acid ester-modified silicones.

[0044] Examples of higher alcohols include isostearyl alcohol, octyldodecanol, stearyl alcohol, cetanol, and behenyl alcohol.

[0045] Examples of higher fatty acids include isostearic acid, oxystearic acid, stearic acid, palmitic acid, behenic acid, myristic acid, and lauric acid.

[0046] Examples of animal and vegetable oils include meadowfoam oil, sunflower oil, macadamia nut oil, avocado oil, linseed oil, almond oil, olive oil, ivota wax, shea butter, cacao butter, carnauba wax, candelilla wax, wheat germ oil, sesame oil, rice germ oil, rice bran oil, safflower oil, shea butter, jojoba oil, soybean oil, camellia oil, eucalyptus oil, evening primrose oil, corn oil, rapeseed oil, rice bran wax, palm kernel oil, castor oil, and beeswax.

[0047] When the component (A) is one or more selected from the group consisting of retinol and its derivatives, the oil agent (B) is preferably one or more selected from the group consisting of vegetable oils and ester oils. Examples of such vegetable oils include meadowfoam oil, sunflower oil, olive oil, shea butter, and macadamia nut oil. Examples of the ester oil include cholesteryl stearate, phytosteryl stearate, cholesteryl isostearate, phytosteryl isostearate, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, long-chain branched fatty acid (12-31) cholesteryl, and tri(caprylic / capric)glycerin.

[0048] Among such (B) oils, more preferably, it is at least one selected from the group consisting of vegetable oils and sterol ester oils, and even more preferably, it is at least one selected from the group consisting of vegetable oils, fatty acid phytosterol ester oils, and fatty acid cholesterol ester oils. More specifically, it is particularly preferably at least one selected from the group consisting of meadowfoam oil, sunflower oil, olive oil, shea butter, macadamia nut oil, cholesteryl stearate, phytosteryl stearate, cholesteryl isostearate, phytosteryl isostearate, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, and long-chain branched fatty acid (12-31) cholesteryl.

[0049] In addition, in the present method for reducing irritation, when one or more types selected from the group consisting of retinol and its derivatives are used as component (A), from the viewpoint of effectively reducing the skin irritation, it is particularly preferable that component (B) be one or more types selected from the group consisting of sunflower oil and long-chain branched fatty acid (12-31) cholesteryl.

[0050] In addition, in the present method for controlling the permeation rate, when one or more selected from the group consisting of retinol and its derivatives are used as the component (A), from the viewpoint of effectively suppressing the percutaneous permeation rate, the component (B) may be selected from sunflower oil, olive oil, shea butter, macadamia nut oil, meadowfoam oil, cholesteryl stearate, phytosteryl stearate, cholesteryl isostearate, phytosteryl isostearate, di(phytosteryl / behenyl / 2-octyldodecyl)-N-lauroyl-L-glutamate, and the like. One or more selected from the group consisting of sunflower oil, di(phytosteryl / behenyl / 2-octyldodecyl) N-lauroyl-L-glutamate, and di(phytosteryl / 2-octyldodecyl) N-lauroyl-L-glutamate are preferred, and one or more selected from the group consisting of sunflower oil, di(phytosteryl / behenyl / 2-octyldodecyl) N-lauroyl-L-glutamate, and di(phytosteryl / 2-octyldodecyl) N-lauroyl-L-glutamate are particularly preferred, and di(phytosteryl / 2-octyldodecyl) N-lauroyl-L-glutamate is most preferred.

[0051] Incidentally, the IOB value of (B) oil agent is the value for each oil agent, and even when two or more oil agents are blended, it means the IOB value of each individual oil agent.

[0052] In this method, the blending amount of the (B) component is 10% by mass or more based on the total amount of the composition for external use on skin, from the viewpoint of achieving the effects of the present invention. Also, the blending amount of the (B) component is preferably 10 to 40% by mass, more preferably 12 to 30% by mass, and even more preferably 15 to 20% by mass, from the viewpoint of achieving the effects of the present invention significantly. When the oil-soluble active ingredient (A) is one or more selected from the group consisting of retinol and its derivatives, the amount of the ingredient (B) is 10% by mass or more, preferably 10 to 40% by mass, and more preferably 12 to 30% by mass, based on the total amount of the topical skin composition.

[0053] In this method, the blending ratio (A / B) of the component (A) to the component (B) is not particularly limited, but from the viewpoint of significantly exhibiting the effects of the present invention, it is, for example, preferably 0.00075 to 0.15, more preferably 0.001 to 0.125, and even more preferably 0.0015 to 0.1. When the oil-soluble active ingredient (A) is one or more selected from the group consisting of retinol and its derivatives, the blending ratio (A / B) of the component (A) to the component (B) is not particularly limited, but from the viewpoint of significantly exhibiting the effects of the present invention, it is, for example, preferably 0.00075 to 0.15, more preferably 0.001 to 0.125, and even more preferably 0.0015 to 0.1.

[0054] From the viewpoints of notably achieving the effects of the present invention and enhancing the ease of spreading of the topical skin composition, the melting point of component (B) is preferably −30 to 80° C., more preferably −25 to 60° C., and even more preferably −20 to 50° C. The melting point of component (B) may be −25 to 10° C. or −20 to 0° C. Furthermore, the melting point of component (B) may be 0 to 70° C. or 20 to 55° C.

[0055] In this method, it is important to use a specific amount of at least one type of (A) component having an IOB value such that the difference between the IOB value of the (A) component and that of the (B) component is within a range of 0.00 to 0.25. Therefore, even when two or more types of (A) components ((A1) component, (A2) component, etc.) are blended, it is sufficient to use a specific amount of (B) component having an IOB value such that the difference between the IOB value of at least one (A) component (e.g., (A1) component) of the two or more (A) components and that of the (A) component (e.g., (A1) component) is within a range of 0.00 to 0.25. For example, it is acceptable if the difference between the IOB value of the other (A) component (e.g., (A2) component) and that of the (B) component is outside the range of 0.00 to 0.25. Of course, as one embodiment of the present method, when two or more kinds of (A) components ((A1) component, (A2) component, etc.) are blended, the IOB values ​​(IOB A1 , I.O.B. A2...) and each difference ("|IOB A1 -IOB B |", "|IOB A2 -IOB B IOB value (IOB | B ) may be used in a specific amount of the (B) component.

[0056] [Other ingredients] In this method, any component other than the components (A) and (B) may be added as long as it does not impair the effects of the present invention. For example, but not limited to, a base, a surfactant, a thickener, an antioxidant, a chelating agent, a pH adjuster, a colorant, an ultraviolet light scattering component, a peptide or a derivative thereof, an amphipathic component, a water-soluble active component, etc. may be added. These may be used alone or in combination of two or more kinds.

[0057] (Base) Examples of the base include aqueous bases such as water (ion-exchanged water, purified water, etc.); lower alcohols such as ethanol and isopropanol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; and polyhydric alcohols such as polyethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin, isoprene glycol, diglycerin, concentrated diglycerin, dipropylene glycol, hexanediol, and pentanediol.

[0058] The amount of the base can be appropriately set depending on the types and amounts of other ingredients, the dosage form, etc., and is not limited, but from the viewpoint of significantly achieving the effects of the present invention, it is, for example, 45 to 90 mass%, 50 to 85 mass%, 55 to 80 mass%, 60 to 75 mass%, etc., relative to the total amount of the topical skin composition.

[0059] The amount of water to be added can be appropriately set depending on the types and amounts of other ingredients, the dosage form, etc., and is not limited, but from the viewpoint of significantly achieving the effects of the present invention, it is, for example, 45 to 85% by mass, 50 to 80% by mass, 55 to 75% by mass, 55 to 70% by mass, etc., relative to the total amount of the topical skin composition.

[0060] The amount of polyhydric alcohol can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but from the viewpoint of significantly achieving the effects of the present invention, it is, for example, 1 to 30 mass%, 2 to 28 mass%, 3 to 25 mass%, 4 to 20 mass%, etc., relative to the total amount of the topical skin composition.

[0061] (Surfactant) Examples of the surfactant include nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, and naturally occurring surfactants.

[0062] The amount of surfactant to be blended can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but from the viewpoint of significantly achieving the effects of the present invention, it is, for example, 0.1 to 5 mass%, 0.2 to 4 mass%, 0.3 to 3 mass%, 0.4 to 2 mass%, etc., relative to the total amount of the topical skin composition.

[0063] Examples of nonionic surfactants include sorbitan fatty acid ester oils such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexyl acid, and diglycerol sorbitan tetra-2-ethylhexyl acid; glycerin fatty acid ester oils such as lipophilic glyceryl monostearate, self-emulsifying glyceryl monostearate, glyceryl monostearate malate, and glyceryl isostearate; and polyglyceryl monostearate. Polyglycerin fatty acid esters such as lyceryl, polyglyceryl monoisostearate, polyglyceryl diisostearate, polyglyceryl monolaurate, polyglyceryl monooleate, and polyglyceryl monomyristate; propylene glycol fatty acid esters such as propylene glycol monostearate; ethylene glycol distearate, ethylene glycol monostearate, triethylene glycol distearate, polyethylene glycol monostearate (2E.O.), polyethylene glycol monostearate Polyethylene glycol monostearate (4 E.O.), Polyethylene glycol monostearate (9 E.O.), Polyethylene glycol monostearate (10 E.O.), Polyethylene glycol monostearate (23 E.O.), Polyethylene glycol monostearate (25 E.O.), Polyethylene glycol monostearate (32 E.O.), Polyethylene glycol monostearate (40 E.O.), Polyethylene glycol monostearate (45 E.O.), Polyethylene glycol monostearate (55 E.O.), Monostearate ethylene glycol fatty acid esters such as polyethylene glycol monostearate (75E.O.), polyethylene glycol monostearate (140E.O.), polyethylene glycol distearate (140E.O.), and polyethylene glycol distearate (250E.O.); hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80 (HCO-80);Polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), polyoxyethylene (20) sorbitan isostearate, and other polyoxyethylene sorbitan fatty acid esters; caprylic acid N-methylethanolamide, capric acid N-methylethanolamide, lauric acid N-methylethanolamide, lauric acid N-ethylethanolamide, lauric acid N -Methylpropanolamide, Lauric acid N-ethylpropanolamide, Lauric acid N-methylisopropanolamide, Lauric acid N-ethylisopropanolamide, Myristic acid N-methylethanolamide, Palmitic acid N-methylethanolamide, Coconut oil fatty acid N-methylethanolamide, Coconut oil fatty acid N-ethylethanolamide, Coconut oil fatty acid N-methylpropanolamide, Coconut oil fatty acid N-ethylpropanolamide, Coconut oil fatty acid N-methylisopropanolamide, Coconut oil fatty acid N-ethylisopropanolamide, Fatty acid alkanolamides such as coconut oil fatty acid diethanolamide, palm kernel oil fatty acid N-methylethanolamide, palm kernel oil fatty acid N-ethylethanolamide, stearic acid N-methylethanolamide, stearic acid N-ethylethanolamide, oleic acid N-methylethanolamide, and oleic acid N-ethylethanolamide; polyoxyethylene monococoate glyceryl; glycerin alkyl ether; hexyl glucoside, capryl glucoside, nonyl glucoside, decyl glucoside, lauryl glucoside, myristyl glucoside Examples of the surfactants include alkyl glucosides such as cetostearyl glucoside, hexadecyl glucoside, octadecyl glucoside, and coconut oil alkyl glucoside; polyoxyalkylene alkyl ethers such as polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, and polyoxyethylene behenyl ether; and silicone surfactants such as lauryl PEG-9 polydimethylsiloxyethyl dimethicone and PEG-9 polydimethylsiloxyethyl dimethicone.

[0064] The amount of the nonionic surfactant can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but is, for example, 0.1 to 5 mass%, 0.2 to 4 mass%, 0.3 to 3 mass%, 0.35 to 2 mass%, 0.4 to 1.5 mass%, etc., relative to the total amount of the topical skin composition.

[0065] Examples of the anionic surfactant include higher fatty acid salts such as sodium palmitate, potassium laurate, sodium myristate, and potassium stearate; alkyl sulfate salts such as sodium lauryl sulfate, triethanolamine lauryl sulfate, sodium laureth sulfate, sodium myristyl sulfate, sodium stearyl sulfate, sodium oleyl sulfate, and sodium cetyl sulfate; polyoxyethylene alkyl ether sulfate salts such as sodium polyoxyethylene lauryl ether sulfate and sodium polyoxyethylene myristyl ether sulfate; alkyl sulfosuccinate salts such as dioctyl sodium sulfosuccinate and disodium lauryl sulfosuccinate; polyoxyethylene alkyl sulfosuccinate salts such as polyoxyethylene lauryl disodium sulfosuccinate; monoalkyl phosphate salts such as sodium lauryl phosphate, sodium cetyl phosphate, and diethanolamine cetyl phosphate; sodium polyoxyethylene lauryl ether phosphate, polyoxyethylene alkyl ether sulfate salts such as dioctyl sodium sulfosuccinate and disodium lauryl sulfosuccinate; polyoxyethylene alkyl ether phosphate salts such as sodium ethyl ether phosphate, sodium polyoxyethylene oleyl ether phosphate, sodium polyoxyethylene alkylphenyl ether phosphate, and polyoxyethylene alkylphenyl ether triethanolamine phosphate; N-acylamino acid salts such as sodium N-lauroyl aspartate, potassium N-cocoyl glutamate, sodium cocoyl glycine, and myristoyl glutamic acid; and alkyl ether glycol acetates such as sodium lauryl glycol acetate (sodium dodecane-1,2-diol acetate), potassium lauryl glycol acetate, sodium myristyl glycol acetate, potassium myristyl glycol acetate, sodium palmityl glycol acetate, potassium palmityl glycol acetate, sodium stearyl glycol acetate, potassium stearyl glycol acetate, sodium behenyl glycol acetate, and potassium behenyl glycol acetate.

[0066] The amount of the anionic surfactant can be appropriately set depending on the types and amounts of other ingredients, the dosage form, etc., and is not limited, but is, for example, 0.0001 to 0.5 mass%, 0.001 to 0.4 mass%, 0.01 to 0.3 mass%, 0.03 to 0.25 mass%, 0.05 to 0.2 mass%, etc., relative to the total amount of the topical skin composition.

[0067] Examples of amphoteric surfactants include coconut oil fatty acid amidopropyl betaine, lauryl hydroxysulfobetaine, lauric acid amidopropyl betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, N-lauroyl-N'-carboxymethyl-N'-hydroxyethyl ethylenediamine sodium, lauramidopropyl hydroxysultaine, lauric acid amidopropyl dimethylamine oxide, and hydroxyalkyl (C12-14) hydroxyethyl sarcosine.

[0068] The amount of amphoteric surfactant blended can be appropriately set depending on the types and amounts of other ingredients, the dosage form, etc., and is not limited, but is, for example, 0.0001 to 3 mass%, 0.001 to 2 mass%, 0.01 to 1 mass%, 0.05 to 0.5 mass%, 0.1 to 0.3 mass%, etc., relative to the total amount of the topical skin composition.

[0069] Examples of cationic surfactants include stearyltrimethylammonium chloride, alkyltrimethylammonium chloride, cetyltrimethylammonium chloride, behenyltrimethylammonium chloride, behenyldimethylhydroxyethylammonium chloride, stearyldimethylbenzylammonium chloride, distearyldimethylammonium chloride, dicetylmethylammonium chloride, cetyltriethylammonium methylsulfate, stearyltrimethylammonium bromide, and cetyltrimethylammonium bromide.

[0070] Examples of naturally occurring surfactants include lecithin, hydrogenated lecithin, saponin, sodium surfactin, and bile acid.

[0071] (Thickener) Examples of the thickening agent include vinyl-based thickening agents such as polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, and carboxyvinyl polymer; cellulose-based thickening agents such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and hydrophobized hydroxypropyl methyl cellulose; guar gum, sclerotium gum, tamarind gum, xanthan gum, dextran, pectin, pullulan, gelatin, locust bean gum, and calcium carbonate; Examples of such surfactants include lageenan, agar, biosaccharide gum, acrylic acid alkyl methacrylate copolymer, sodium polyacrylate, polyacrylic acid amide, bentonite, dextrin fatty acid ester, dimethyl distearyl ammonium hectorite, sodium alginate, polyethylene glycol, trimethylammonium chloride hydroxypropyl guar gum, trimethylammonio chloride hydroxypropyl hydroxyethyl cellulose, (hydroxyethyl acrylate / sodium acryloyldimethyl taurate) copolymer, (ammonium acryloyldimethyl taurate / vinyl pyrrolidone) copolymer, etc.

[0072] The amount of thickener to be blended can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but may be, for example, 0.001 to 6 mass%, 0.01 to 5 mass%, 0.05 to 4 mass%, 0.1 to 3 mass%, etc., relative to the total amount of the topical skin composition.

[0073] (Antioxidants) Examples of antioxidants include butylhydroxyanisole, sorbic acid, sodium sulfite, sodium ascorbate, dl-α-tocopherol, tocotrienol, hydrogen sulfite, sodium hyposulfite, erythorbic acid, sodium erythorbate, and L-cysteine ​​hydrochloride. The amount of the antioxidant can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but may be, for example, 0.001 to 3 mass%, preferably 0.005 to 2.5 mass%, more preferably 0.01 to 2 mass%, 0.1 to 1 mass%, etc., relative to the total amount of the topical skin composition.

[0074] (chelating agent) Examples of the chelating agent include EDTA disodium salt and EDTA calcium disodium salt. The amount of the chelating agent can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but is, for example, 0.001 to 2.5 mass%, preferably 0.005 to 2 mass%, and more preferably 0.01 to 1 mass% of the total amount of the topical skin composition.

[0075] (pH adjuster) Examples of pH adjusters include inorganic bases such as potassium hydroxide, sodium hydroxide, and sodium carbonate; organic bases such as triethanolamine, diisopropanolamine, and triisopropanolamine; inorganic acids such as hydrochloric acid and sulfuric acid; and organic acids such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, and sodium succinate. The content of the pH adjuster can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but is, for example, 0.001 to 2.5 mass%, preferably 0.005 to 2 mass%, and more preferably 0.01 to 1 mass% relative to the total amount of the topical skin composition.

[0076] (Coloring agent) Examples of colorants include inorganic pigments and natural dyes. The amount of colorant blended can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but is, for example, 0.001 to 1 mass %, preferably 0.005 to 0.1 mass %, and more preferably 0.01 to 0.05 mass % relative to the total amount of the topical skin composition.

[0077] (Ultraviolet scattering component) Examples of ultraviolet scattering components include inorganic compounds such as hydrous silicic acid, zinc silicate, cerium silicate, titanium silicate, zirconium oxide, cerium oxide, titanium oxide, iron oxide, and anhydrous silicic acid; these inorganic compounds are coated with inorganic powders such as hydrous silicic acid, aluminum hydroxide, mica, and talc; or are composited with resin powders such as polyamide, polyethylene, polyester, polystyrene, and nylon; and further treated with silicone oil, aluminum salt of a fatty acid, or the like. The content of the ultraviolet absorbing component can be appropriately set depending on the type and amount of other components, the dosage form, etc., and is not limited, but is, for example, 1 to 30 mass %, preferably 3 to 25 mass %, and more preferably 5 to 20 mass % relative to the total amount of the topical skin composition.

[0078] (Peptide or its derivative) Examples of peptides or derivatives thereof include keratin hydrolyzed peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin hydrolyzed peptides, collagen hydrolyzed peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin hydrolyzed peptides, conchiolin hydrolyzed peptides, hydrolyzed conchiolin, silk proteolytic peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soybean proteolytic peptides, hydrolyzed soybean protein, casein hydrolyzed peptides, acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.), and the like. The content of the peptide or its derivative can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but is, for example, 0.001 to 5 mass%, preferably 0.01 to 3 mass%, and more preferably 0.05 to 1 mass% relative to the total amount of the topical skin composition.

[0079] (Amphiphilic component) Examples of the amphiphilic component include 2-methacryloyloxyethyl phosphorylcholine-butyl methacrylate copolymer liquid, 2-methacryloyloxyethyl phosphorylcholine-stearyl methacrylate copolymer, and the like. The content of the amphiphilic component can be appropriately set depending on the type and amount of other components, the dosage form, etc., and is not limited, but is, for example, 0.01 to 5 mass%, preferably 0.1 to 3 mass%, and more preferably 0.5 to 2 mass% relative to the total amount of the topical skin composition.

[0080] (Water-soluble active ingredient) Examples of water-soluble active ingredients include mucopolysaccharides such as hyaluronic acid, chondroitin sulfate, heparin, heparin-like substances, their decomposition products and their salts; ascorbic acid such as 3-O-ethyl ascorbic acid, its derivatives and their salts; collagen and its decomposition products; proteoglycan and its decomposition products; plant-derived proteins and their decomposition products; nicotinic acid, its derivatives and their salts; tranexamic acid, glycyrrhizinic acid, azelaic acid, etc. The content of the water-soluble active ingredient can be appropriately set depending on the type and amount of other ingredients, the dosage form, etc., and is not limited, but is, for example, 0.01 to 5 mass%, preferably 0.1 to 3 mass%, and more preferably 0.2 to 2 mass% relative to the total amount of the topical skin composition.

[0081] In this method, when a specific (A) component and a (B) component having an IOB value whose difference from the IOB value of the (A) component is within the range of 0.00 to 0.25 are mixed together with an oil (hereinafter sometimes referred to as a (B') component) having an IOB value whose difference from the IOB value of the (A) component is outside the range of 0.00 to 0.25, the amount of the oil can be appropriately set depending on the types and amounts of other components, the dosage form, etc., and is not limited to, but is, for example, less than 10 mass%, preferably less than 5 mass%, more preferably less than 3 mass%, and even more preferably less than 2 mass% of the total amount of the topical skin composition.

[0082] In addition, in the present method, when the (B') component is blended, the blending ratio (B' / B) of the (B) component to the (B') component blended in the topical skin composition is not particularly limited, but is, for example, preferably 0.001 to 1.5, more preferably 0.005 to 1.0, and even more preferably 0.01 to 0.8.

[0083] [Preparation method] In this method, component (A), component (B), and other components are prepared in a conventional manner, for example by mixing and stirring, into an oil-in-water (O / W) or water-in-oil (W / O) skin topical composition. From the viewpoint of achieving the most pronounced effects of the present invention, an oil-in-water (O / W) skin topical composition is preferred.

[0084] [Viscosity of topical skin composition] The viscosity (25°C) of the composition for external use on skin obtained using this method can be appropriately set depending on the dosage form, etc., and is not limited, but is, for example, preferably 200 to 500,000 mPa·s, more preferably 2,000 to 400,000 mPa·s, and even more preferably 20,000 to 300,000 mPa·s.

[0085] The viscosity (25°C) is measured using a single cylindrical rotational viscometer (Brookfield viscometer) in accordance with the viscosity measurement method described in the general test method of the Japanese Pharmacopoeia, 18th Edition. Specifically, it is a value measured using a TV-10H (manufactured by Toki Sangyo Co., Ltd.), and the selection of conditions such as the rotor and rotation speed is in accordance with the instruction manual for this device, and the viscosity is measured at 25°C.

[0086] The single cylinder rotational viscometer is described below. A single cylinder rotational viscometer is a viscometer that measures the torque when a cylinder in a liquid is rotated at a constant angular velocity. The viscosity of the liquid, η, is calculated by the following formula, by determining the device constant KB experimentally in advance using a standard liquid for calibrating the viscometer. η=KB×T / ω η: Viscosity of the liquid (mPa s) KB: Equipment constant (rad / cm 3 ) ω: Angular velocity (rad / s) T: Torque acting on the cylindrical surface (10 -7 N m)

[0087] [pH of topical skin composition] The pH of the topical skin composition obtained using this method can be set appropriately depending on the dosage form, etc., and is not limited to a specific value. For example, the pH is preferably 4.0 to 9.0, more preferably 4.5 to 8.5, even more preferably 4.8 to 8.0, and particularly preferably 5.0 to 7.5. The pH is measured using a pH meter (for example, pH METER F-52 (manufactured by HORIBA) at room temperature (23° C.)).

[0088] [Percutaneous permeation inhibition rate of topical skin composition] The percutaneous permeation rate of the skin topical composition obtained by this method can be evaluated, for example, by the percutaneous permeation inhibition rate shown in the Examples below. The percutaneous permeation inhibition rate is preferably 30% or more. The percutaneous permeation inhibition rate is more preferably 45% or more, even more preferably 50% or more, particularly preferably 55% or more, particularly preferably 60% or more, and most preferably 70% or more.

[0089] [Form of formulation, etc.] The form of the skin external composition obtained by the present method is not particularly limited, and may be, for example, liquid, fluid, or semi-solid. Examples of the formulation form include liquid, suspension, emulsion, cream, milky lotion, ointment, gel, liniment, lotion, sheet in which nonwoven fabric is impregnated with cosmetics, mist, stick, foam, etc.

[0090] [Applications, parts used] The skin topical composition obtained by the present method is used in cosmetics, quasi-drugs, medicines, etc. Specific examples include basic cosmetics such as lotion, milky lotion, gel, cream, beauty essence, sunscreen cosmetics, packs, masks, hand cream, body lotion, and body cream; cleansing cosmetics such as face wash, hand soap, makeup remover, body shampoo, shampoo, rinse, and treatment; face makeup cosmetics such as foundation and makeup base; lip cosmetics, etc. The site of use is not particularly limited, and it is used, for example, on the face, body, scalp, etc. for skin care purposes.

[0091] [container] The skin topical composition obtained by the present method can be filled into a container appropriately selected according to the purpose and application, and used. Examples of the container include bottles, tubes, jars, dispensers, pouches, and cheer packs. Examples of materials constituting the container include polyethylene terephthalate, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metal (aluminum, etc.), and mixtures thereof. In addition, containers formed from these materials can be subjected to various coating treatments on the container surface, for example, in consideration of strength, flexibility, weather resistance, or stability of the components. In addition, the container can be formed by laminating films formed from the above materials.

[0092] <Skin irritation relief agent for ingredient (A)> One embodiment of the present invention is a skin irritation mitigating agent used to mitigate the skin irritation of an oil-soluble active ingredient (A) such as retinol that is blended into a composition for external use on the skin. That is, a skin irritation mitigating agent used to mitigate the skin irritation of an oil-soluble active ingredient (A) such as retinol that is blended into a composition for external use on the skin, the skin irritation mitigating agent including an oil (B) having an IOB value that differs from the IOB value of the oil-soluble active ingredient (A) by 0.00 to 0.25, and which mitigate the skin irritation of the oil-soluble active ingredient (A).

[0093] A preferred embodiment of the above-mentioned embodiment is a skin irritation mitigating agent used to mitigate skin irritation of one or more selected from the group consisting of retinol and its derivatives incorporated in a skin topical composition, the skin irritation mitigating agent including one or more selected from the group consisting of meadowfoam oil, sunflower oil, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, and long-chain branched fatty acid (12-31) cholesteryl.

[0094] Further, examples of the skin irritation mitigating agent include a skin irritation mitigating agent used to mitigate skin irritation with one or more selected from the group consisting of retinol and its derivatives, which are contained in an amount of 0.03% by mass or more relative to the total amount of the topical skin composition, and which contains one or more selected from the group consisting of meadowfoam oil, sunflower oil, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, and long-chain branched fatty acid (12-31) cholesteryl.

[0095] In addition, one embodiment of the present invention includes a skin topical composition containing a skin irritation mitigating agent. For example, a skin topical composition with reduced skin irritation may include a skin irritation mitigating agent containing one or more selected from the group consisting of retinol and its derivatives, and one or more selected from the group consisting of meadowfoam oil, sunflower oil, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, and long-chain branched fatty acid (12-31) cholesteryl, in which the amount of one or more selected from the group consisting of retinol and its derivatives is 0.03% by mass or more based on the total amount of the skin topical composition, and the amount of the skin irritation mitigating agent is 10% by mass or more based on the total amount of the skin topical composition.

[0096] <(A) Transdermal penetration rate regulator, etc.> One embodiment of the present invention is a percutaneous penetration rate control agent used to control the percutaneous penetration rate of an oil-soluble active ingredient (A) blended in a composition for external use on skin. That is, a percutaneous penetration rate control agent used to control the percutaneous penetration rate of an oil-soluble active ingredient (A) blended in a composition for external use on skin, which includes an oil (B) having an IOB value that is 0.00 to 0.25 different from the IOB value of the oil-soluble active ingredient (A), controls the percutaneous penetration rate of the oil-soluble active ingredient (A).

[0097] A preferred embodiment of the above-mentioned embodiment is a transdermal permeation rate control agent used to control the transdermal permeation rate of one or more selected from the group consisting of retinol and its derivatives incorporated in a skin topical composition, the transdermal permeation rate control agent including one or more selected from the group consisting of meadowfoam oil, sunflower oil, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, and long-chain branched fatty acid (12-31) cholesteryl.

[0098] Further, examples of the percutaneous permeation rate control agent include a percutaneous permeation rate control agent used for controlling the percutaneous permeation rate of one or more selected from the group consisting of retinol and its derivatives, which are contained in an amount of 0.03% by mass or more based on the total amount of the composition for external use on skin, and which contains one or more selected from the group consisting of meadowfoam oil, sunflower oil, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, and long-chain branched fatty acid (12-31) cholesteryl.

[0099] In addition, one embodiment of the present invention includes a skin topical composition containing a percutaneous penetration rate control agent. For example, a skin topical composition containing one or more selected from the group consisting of retinol and its derivatives, and a percutaneous penetration rate control agent containing one or more selected from the group consisting of meadowfoam oil, sunflower oil, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, and long-chain branched fatty acid (12-31) cholesteryl, in which the amount of one or more selected from the group consisting of retinol and its derivatives is 0.03% by mass or more based on the total amount of the skin topical composition, and the amount of the percutaneous penetration rate control agent is 10% by mass or more based on the total amount of the skin topical composition, and the percutaneous penetration rate control agent is suppressed.

[0100] <Design and manufacturing method of topical skin composition containing skin irritation mitigating agent, etc.> One embodiment of the present invention is a method for producing an external skin composition, comprising: a first step of designing a formulation for an external skin composition, the first step including a step of selecting an oil-soluble active ingredient (A) such as retinol, and a step of selecting one or more skin irritation mitigating agents based on the IOB value of the selected oil-soluble active ingredient (A); and a second step of preparing the external skin composition according to the formulation, wherein the step of selecting the skin irritation mitigating agent is a step of selecting an oil (B) having an IOB value that differs from the IOB value of the oil-soluble active ingredient (A) by 0.00 to 0.25.

[0101] One embodiment of the present invention is a method for producing an external skin composition, comprising a first step of designing a formulation for an external skin composition, the first step including a step of selecting an oil-soluble active ingredient (A) such as retinol, and a step of selecting one or more transdermal permeation rate control agents based on the IOB value of the selected oil-soluble active ingredient (A), and a second step of preparing the external skin composition according to the formulation, wherein the step of selecting the transdermal permeation rate control agent is a step of selecting an oil (B) having an IOB value that differs from the IOB value of the oil-soluble active ingredient (A) by 0.00 to 0.25. EXAMPLES

[0102] The present invention will be described in more detail below, but the present invention is not limited thereto. Note that the unit of the blending amount in Table 2 showing the examples and the like described later and in the formulation examples is mass %, and all values ​​are calculated as pure content. The total amount of each composition is 100 mass %.

[0103] <Examples 1 to 9> First, retinol (IOB value: 0.32) was selected as component (A) for which reduction in skin irritation and / or control of transdermal penetration rate is required.

[0104] Next, the difference with the IOB value of retinol (|IOB A -IOB B As the (B) oils having an IOB value in the range of 0.00 to 0.25, meadowfoam oil, sunflower oil, N-lauroyl-L-glutamic acid di(phytosteryl / behenyl / 2-octyldodecyl), N-lauroyl-L-glutamic acid di(phytosteryl / 2-octyldodecyl), macadamia nut oil fatty acid phytosteryl, long-chain branched fatty acid (12-31) cholesteryl, and tri(caprylic / capric)glycerin were selected. The IOB value of the (B) component and the ΔIOB value (|IOB A -IOB B |) are shown in Table 1.

[0105] [Table 1]

[0106] As described above, the (B) component was selected based on the IOB value of the (A) component, and each formulation shown in the following Table 2 was designed. Next, according to the formulation, the skin topical compositions according to Examples 1 to 9 and a control skin topical composition (hereinafter sometimes referred to as "control") were prepared by a conventional method. Each of the prepared skin topical compositions was evaluated for skin irritation, percutaneous penetration rate, and usability (ease of application and spreading). In addition, in order to clarify the excellent effects of the present invention, a control formulation was prepared that contained oleosomes (Botaneco, Hydresia SF2), a component that suppresses the transdermal penetration rate of oil-soluble active ingredients and exhibits sustained release properties.

[0107] <Skin irritation> Five expert panelists evaluated the skin irritation when each skin topical composition was applied to the skin. Specifically, 20 μl of each skin topical composition was applied to the inside of the upper arm of five expert panelists, and the irritation sensation immediately after application was evaluated on a 5-point scale from 1 to 5. The average score (1 to 5) of each expert panelist was calculated and evaluated according to the following criteria. The results are shown in Table 2. [Score] 1: It doesn't hurt. 2: Almost no pain. 3: I can't say either way. 4: I feel a little pain. 5: It hurts. [Evaluation Criteria] ◎: Average score is 1 or more and less than 2 〇…Average score is 2 or more but less than 3 △: Average score is 3 or more but less than 4 ×: Average score is 4 or more and 5 or less

[0108] <Transdermal penetration rate> The percutaneous penetration rate was evaluated based on the amount of retinol permeated percutaneously contained in each skin topical composition. Specifically, 400 μl of each skin topical composition was added to the skin surface of a three-dimensional human skin model (manufactured by LabCyte, product name LabCyte EPI-MODEL24) and left to stand for 4 hours in a CO2 incubator (product number: MCO-170AICUVH-PJ) manufactured by pHcbi. After the above treatment, the skin surface was washed with 5 to 7.5 ml of PBS, epidermal cells were collected, and then 5 ml of ethanol containing 0.1% BHT was added, and retinol in the epidermal cells was extracted by ultrasonic treatment for 5 minutes and quantified by HPLC. The results are shown in Table 2. The HPLC analysis conditions are as follows. Detector: Fluorescence detector Excitation wavelength 340nm, Fluorescence wavelength 460nm Column: Inertsil ODS-2 (4.6mm x 250mm, particle size 5μm) Column temperature: 40℃ Mobile phase: Ethanol / water mixture (volume ratio 95 / 5) ·Flow rate: 1.0mL / min ·Injection volume: 10μL Analysis cycle: 6 minutes

[0109] Using the percutaneous permeation amount of the control as a control, the percutaneous permeation inhibition rate (%) of each of the external skin compositions of Examples 1 to 9 was calculated using the following formula and evaluated according to the following criteria. The results are shown in Table 2. (Percutaneous penetration inhibition rate) Percutaneous permeation inhibition rate (%) = (percutaneous permeation amount of control - percutaneous permeation amount of topical skin composition) / percutaneous permeation amount of control x 100 (Evaluation Criteria) ◎...Transdermal penetration inhibition rate of 50% or more ○…Percutaneous penetration inhibition rate: 30% or more, less than 50% △: Percutaneous penetration inhibition rate: over 0% and under 30% ×: Percutaneous penetration inhibition rate 0% or less

[0110] <Usability (ease of application)> Five expert panelists evaluated the usability (ease of spreading) of each skin topical composition when applied to the skin. Specifically, 20 μl of each skin topical composition was applied to the inside of the upper arm of five expert panelists, and the ease of spreading during application was evaluated on a 5-point scale from 1 to 5. The average score (1 to 5) of each expert panelist was calculated and evaluated according to the following criteria. The results are shown in Table 2. [Score] 5: I feel it is easy to spread. 4: I feel it is somewhat easy to spread. 3: I can't say either way. 2: It feels a little difficult to spread. 1: It is difficult to spread. [Evaluation Criteria] ◎: Average score is 4 or more and 5 or less 〇…Average score is 3 or more but less than 4 △: Average score is 2 or more but less than 3 ×: Average score is 1 or more and less than 2

[0111] [Table 2]

[0112] As shown in Table 2, it was confirmed that the skin irritation of component (A) was alleviated in Examples 1 to 9 obtained using the present method. Specifically, it was confirmed that Examples 1 to 9 had a significantly greater effect of alleviating irritation (evaluation: ◯ or ◎) than the skin irritation of the control using oleosome (evaluation: ×), and were able to alleviate skin irritation to a high level.

[0113] It was also confirmed that Examples 1 to 9 of the present invention had a high percutaneous permeation inhibition rate of component (A) and the percutaneous permeation rate was inhibited or reduced. Specifically, the percutaneous permeation inhibition rates of Examples 1 to 9 of the present invention were at least 30% or more (specifically, within the range of 45 to 85%) based on the percutaneous permeation amount of the control using oleosome, and it was confirmed that the percutaneous permeation inhibition effect was significantly greater than that of the control using oleosome, and the percutaneous permeation rate could be inhibited at a high level.

[0114] Furthermore, as shown in Table 2, it was confirmed that Examples 1 to 9 obtained using this method were easy to spread.

[0115] From the above, it was confirmed that by using a method in which the difference between the IOB value of component (A) and the IOB value of component (B) is 0.00 to 0.25 and the amount of component (B) is 10 mass% or more relative to the total amount of the topical skin composition, it is possible to provide a method for effectively alleviating the skin irritation of component (A) and / or a method for effectively controlling the transdermal penetration rate of component (A).

[0116] Examples of formulations obtained by each method of the present invention are given below.

[0117] [Table 3]

[0118]

Table 4

Claims

1. A method for reducing the skin irritation of an oil-soluble active ingredient (A) contained in a composition for external use on the skin by using an oil agent (B), comprising: A ) and the IOB value of the (B) oil solution (IOB B ) and the difference (|IOB A -IOB B |) in the range of 0.00 to 0.25, and the oil agent (B) is blended in an amount of 10 mass% or more based on the total amount of the composition for external use on skin, thereby reducing the skin irritation caused by the oil-soluble active ingredient (A).

2. A method for controlling the percutaneous penetration rate of an oil-soluble active ingredient (A) incorporated in a composition for external use on the skin by using an oil agent (B), comprising: A ) and the IOB value of the (B) oil solution (IOB B ) and the difference (|IOB A -IOB B |) in the range of 0.00 to 0.25, and the oil agent (B) is blended in an amount of 10 mass% or more based on the total amount of the composition for external use on skin, thereby controlling the transdermal penetration rate of the oil-soluble active ingredient (A).

3. 3. The method according to claim 1 or 2, wherein the oil-soluble active ingredient (A) is one or more selected from the group consisting of retinol and its derivatives.

4. The method according to claim 3, wherein the amount of the one or more selected from the group consisting of retinol and its derivatives is 0.03% by mass or more based on the total amount of the topical skin composition.

5. The IOB value of the (B) oil solution (IOB B 5. The method of claim 4, wherein the ratio of the stoichiometric ... to the total stoichiometric ratio is 0.07 to 0.

32.

6. The method according to claim 5, wherein the oil (B) is at least one oil selected from the group consisting of vegetable oils and sterol ester oils.

7. The method according to claim 6, wherein the topical skin composition is an oil-in-water type topical skin composition.

8. A skin irritation mitigating agent used for mitigating the skin irritation of an oil-soluble active ingredient (A), comprising an oil agent (B) having an IOB value that differs from the IOB value of the oil-soluble active ingredient (A) by 0.00 to 0.25.

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