JP2023020034A - External preparation for skin - Google Patents

Abstract

To provide an external preparation for skin which enhances skin permeability of cannabidiol by incorporating (a) cannabidiol and (b) an oil solution (provided that a hydrocarbon oil and a silicone oil are excluded) after finding an external preparation for skin having a percutaneous absorption promoting action of cannabidiol.SOLUTION: Permeability of cannabidiol to the skin can be enhanced by blending an oil solution (provided that a hydrocarbon oil and a silicone oil are excluded) as a percutaneous absorption enhancer of cannabidiol in an external preparation for skin which contains (a) cannabidiol and (b) an oil solution (provided that a hydrocarbon oil and a silicone oil are excluded).SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to an external preparation for skin containing cannabidiol and a specific oil. More specifically, it relates to an external preparation for skin characterized by increasing the permeation of cannabidiol into the skin, and more specifically, it contains cannabidiol and oil (excluding hydrocarbon oil and silicone oil). The present invention relates to an external preparation for skin characterized by containing an oil agent for the purpose of increasing the permeability of cannabidiol to the skin.

Cannabidiol (CBD) is attracting attention as an ingredient expected to have a new pharmacological action. Cannabidiol is one of the cannabinoids contained in hemp, and for example, therapeutic agents for epileptic seizures, therapeutic compositions for tuberous sclerosis, and the like have been developed (Patent Documents 1 and 2). It is also being developed for use as an external agent.

However, since cannabidiol is a highly lipophilic compound, it has low permeability to the skin and is difficult to be absorbed through membranes such as the skin. Therefore, there is a demand for an external preparation for skin with improved percutaneous absorption of cannabidiol.

Japanese translation of PCT publication No. 2013-523708 Japanese Patent Publication No. 2017-537064

Accordingly, an object of the present invention is to provide an external preparation for skin in which the absorption effect of cannabidiol into the skin and mucous membranes is enhanced.

The inventors of the present invention conducted studies on cannabidiol percutaneous absorption of various substances in order to find a cannabidiol-containing external skin preparation that is excellent in enhancing the percutaneous absorption of cannabidiol. rice field. As a result, the present inventors have found that oils other than hydrocarbon oils and silicone oils have an excellent percutaneous absorption-enhancing effect of cannabidiol, leading to the completion of the present invention. That is, the present invention relates to an external preparation for skin characterized by containing cannabidiol and an oil agent (excluding hydrocarbon oil and silicone oil). The present invention also provides an external preparation for skin characterized by containing cannabidiol and an oil agent (excluding hydrocarbon oil and silicone oil), which has a percutaneous absorption promoting effect of cannabidiol. (excluding hydrocarbon oils and silicone oils).

The outline of the present invention is as follows.
[1] An external skin preparation comprising (a) cannabidiol and (b) an oil (excluding hydrocarbon oil and silicone oil).
[2] The external preparation for skin according to [1], wherein the component (b) is at least one selected from ester oils and oils.
[3] Ester oil in which the component (b) consists of a fatty acid having 8 to 24 carbon atoms and an aliphatic alcohol having 3 to 24 carbon atoms, or an ester oil consisting of a polyhydric alcohol having 2 or more carbon atoms and a fatty acid having 8 to 24 carbon atoms. , and an ester oil comprising a dicarboxylic acid and an aliphatic alcohol having 3 to 18 carbon atoms.
[4] The external preparation for skin according to any one of [1] to [3], wherein component (b) is an oil having a solubility parameter (SP value) of 16.5 to 22.0.
[5] The component (b) is at least one selected from isotridecyl isononanoate, neopentyl glycol dicaprate, diisostearyl malate, isopropyl myristate, and polyglyceryl-2 diisostearate [3] and the skin external preparation according to any one of [4].
[6] The external preparation for skin according to any one of [1] to [5], further comprising (c) a polyhydric alcohol.
[7] The external preparation for skin according to any one of [1] to [6], further comprising (d) an alkylene oxide adduct of glycerin and/or diglycerin.
[8] The external preparation for skin according to any one of [1] to [7], which is an emulsion.
[9] The external preparation for skin according to [8], which is an oil-in-water emulsion.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an external preparation for skin in which the permeability of cannabidiol to the skin is enhanced. In particular, in an external skin preparation containing cannabidiol and an oil (excluding hydrocarbon oil and silicone oil), the oil (excluding hydrocarbon oil and silicone oil) is blended as a skin absorption enhancer for cannabidiol. Thereby, the permeability of cannabidiol to the skin can be enhanced. Further, according to the present invention, in the external skin preparation that is an emulsion containing cannabidiol and an oil (excluding hydrocarbon oil and silicone oil), the oil (excluding hydrocarbon oil and silicone oil) is added. By blending as a skin absorption enhancer for cannabidiol, the permeability of cannabidiol to the skin can be increased. Further, according to the present invention, the external preparation for skin, which is an oil-in-water emulsion containing cannabidiol and an oil (excluding hydrocarbon oil and silicone oil), includes: ) as a skin absorption enhancer for cannabidiol, the permeability of cannabidiol to the skin can be increased. In addition, according to the present invention, an external skin preparation containing cannabidiol and an oil (excluding hydrocarbon oil and silicone oil) and a polyhydric alcohol further includes an oil (excluding hydrocarbon oil and silicone oil). ) and a polyhydric alcohol as a skin absorption enhancer for cannabidiol, the permeability of cannabidiol to the skin can be further increased. In addition, according to the present invention, in a skin external preparation containing cannabidiol and an oil (excluding hydrocarbon oil and silicone oil) and further an alkylene oxide addition derivative of glycerin and/or diglycerin, the oil (provided that excluding hydrocarbon oils and silicone oils), and alkylene oxide adducts of glycerin and/or diglycerin as skin absorption enhancers of cannabidiol, the permeability of cannabidiol to the skin can be further increased. can.

The present invention provides an external preparation for skin characterized by containing cannabidiol and an oil (excluding hydrocarbon oil and silicone oil), wherein the oil has a skin absorption promoting effect of cannabidiol. excluding hydrocarbon oils and silicone oils).

(a) Cannabidiol The external preparation for skin of the present invention is characterized by containing cannabidiol. Cannabidiol is a kind of cannabinoid and is known to be contained in hemp. Cannabidiol is known to have different pharmacological effects from the same cannabinoid, tetrahydrocannabinol. In the present invention, cannabidiol can be extracted and purified from plants such as hemp and citrus peels, or synthesized. It is preferable to use those purified from natural products or those synthesized from the viewpoint of enhancing action and whitening action.

The content of cannabidiol in the external skin preparation of the present invention is not particularly limited, and is preferably 0.000001% by mass or more, more preferably 0.00001% by mass or more, and has high cell activating action, anti-aging action, and rough skin improvement. It is particularly preferably 0.001% by mass or more from the viewpoint of obtaining action and whitening action. In addition, it is preferably 10% by mass or less, more preferably 5% by mass or less, and particularly preferably 3% by mass or less from the viewpoint of obtaining high cell activating action, anti-aging action, rough skin improving action and whitening action.

(b) Oil agent The external preparation for skin of the present invention is characterized by containing an oil agent (excluding hydrocarbon oil and silicone oil) together with cannabidiol. The oil agent used in the present invention may be any oil agent that can be applied to the skin and used, and may be either polar or non-polar. In addition, it may be liquid or solid at room temperature (20° C.) and is not particularly limited, but from the viewpoint of obtaining cannabidiol's skin absorption promoting action, cell activating action, anti-aging action, rough skin improving action, and whitening action. Oils that are liquid at room temperature are preferred.

The oil agent used in the present invention is not particularly limited as long as it is an oil agent other than hydrocarbon oil and silicone oil. Examples of oil agents include higher fatty acids, higher alcohols, ester oils, waxes, and fats and oils, from the viewpoint of obtaining cannabidiol's skin absorption promoting action, cell activating action, anti-aging action, rough skin improving action, and whitening action. Ester oils and fats are preferred, and ester oils are particularly preferred.

When the oil agent used in the present invention is an ester oil, it is not particularly limited as long as it is an oily component synthesized using an esterification reaction. , ester oils composed of fatty acids having 8 to 24 carbon atoms and fatty alcohols having 3 to 24 carbon atoms from the viewpoint of obtaining a whitening effect, ester oils composed of polyhydric alcohols having 2 or more carbon atoms and fatty acids having 8 to 24 carbon atoms. , and ester oils composed of a dicarboxylic acid and an aliphatic alcohol having 3 to 18 carbon atoms are preferred.

Specific examples of ester oils include isopropyl isostearate, isotridecyl isononanoate, cetyl-1,3-dimethylbutyl ether, butyl stearate, octyldodecyl myristate, cetyl isobutyl ether, isopropyl palmitate, myristyl myristate, dioctyl ether, isostearyl myristate, isotridecyl isononanoate, isopropyl palmitate, triisostearin, alkyl-1,3-dimethylbutyl ether, di(cholesteryl/octyldodecyl) N-lauroyl-L-glutamate, neopentyl glycol dicaprate, alkyl benzoate ( C12-C15), triethylhexanoin, trisethoxydiglycol phosphate, glyceryl monomyristate monoisostearate, octyldodecyl lactate, 2-ethylhexyl paramethoxycinnamate, diisostearyl malate, glyceryl tri-2-ethylhexanoate , isopropyl myristate, diglyceryl diisostearate, polyglyceryl-2 diisostearate, 2-ethylhexyl 4-methoxycinnamate, glyceryl monomyristate monoisostearate, 2-ethylhexyl paramethoxycinnamate, polyglyceryl-10 diisostearate, dl -α-tocopherol, monoglyceride oleate, diglyceryl monoisostearate, tri(caprylic/capric)glyceryl, isotridecyl isononanoate, neopentyl glycol dicaprate, diisostearyl malate, isopropyl myristate , polyglyceryl-2 diisostearate are preferred.

When the oil agent used in the present invention is a fat, it is not particularly limited as long as it is a substance mainly composed of triglycerides of glycerin and higher fatty acids. ℃), it may be either a liquid fatty oil or a solid fat at normal temperature, and there is no particular limitation, but cannabidiol can provide skin absorption promoting action, cell activation action, anti-aging action, rough skin improving action, and whitening action. From the point of view, vegetable oils and fats are preferred, and vegetable oils are particularly preferred. Vegetable fatty oils include, for example, Amazuna seed oil, avocado oil, almond oil, olive fruit oil, kukui nut oil, hydrogenated castor oil, sesame oil, wheat germ oil, rice bran oil, soybean oil, evening primrose oil, camellia seed oil, corn oil. , Rapeseed Oil, Apricot Kernel Oil, Palm Oil, Coix Seed Oil, Castor Oil, Sunflower Seed Oil, Grape Seed Oil, Hazelnut Oil, Jojoba Seed Oil, Macadamia Seed Oil, Meadowfoam Oil, Cottonseed Oil, Coconut Oil, Peanut Oil, Rose Canina Fruit Oil, tea seed oil, lavender oil and the like can be mentioned, and kukui nut oil, hydrogenated castor oil, jojoba seed oil and coconut oil are preferred.

The oil used in the present invention (excluding hydrocarbon oil and silicone oil) preferably has a solubility parameter (SP value) of 16.5 to 22.0 (cal/cm ³ )1/2. The SP value is the solubility parameter δ, which is a substance constant obtained from the molecular cohesive energy E and the molecular volume V of the liquid as δ=(E/V) 1/2 (J/cm ³ ). From this value it is possible to deduce the relative polarity of the substance. The SP value is determined by actual measurement or calculation by various methods, for example, according to the method of Fedors, using the parameters shown in J. BRANDR UP, "POLYMER HANDBOOK 4th" (published by JHON WILEY & SONS, INC., 1999), paragraphs VII 685-686. is required. When the external skin preparation of the present invention is a mixture of oils, the SP value of component (b) is a weighted average, that is, the sum of the products of the SP values and mass fractions of the constituent components. In addition, when the oil agent in the external preparation for skin of the present invention is a natural product, a polymer, or the like whose structural formula cannot be specified, the SP value of the component (b) is calculated according to the representative structure.

The oil with an SP value of 16.5 to 22.0 used in the present invention is not particularly limited as long as the SP value is 16.5 to 22.0, but preferably 16.7 to 21.5. 17.0 to 21.0 is particularly preferred from the viewpoint of obtaining skin absorption promoting action, cell activating action, anti-aging action, rough skin improving action and whitening action.

Examples of oils having an SP value of 16.5 to 22.0 include isopropyl isostearate (SP value 16.6), isotridecyl isononanoate (SP value 16.6), cetyl-1,3-dimethylbutyl ether (SP value 16 .6), butyl stearate (SP value 16.7), octyldodecyl myristate (SP value 16.7), cetyl isobutyl ether (SP value 16.8), isopropyl palmitate (SP value 16.8), myristine myristyl acid (SP value 16.8), dioctyl ether (SP value 16.9), isostearyl myristate (SP value 16.9), isotridecyl isononanoate (SP value 17.0), isopropyl palmitate (SP value 17 .0), dimethicone (10cs) (SP value 17.0), triisostearin (SP value 17.1), alkyl-1,3-dimethylbutyl ether (SP value 17.2), isostearic acid (SP value 17.5 ), N-lauroyl-L-glutamic acid di (cholesteryl octyldodecyl) (SP value 17.5), isopalmitic acid (SP value 17.6), oleic acid (SP value 17.6), linoleic acid (SP value 17.6), isomyristic acid (SP value 17.7), neopentyl glycol dicaprate (SP value 17.7), alkyl benzoate (C12-C15) (SP value 18.0-18.2), triethyl Hexanoin (SP value 18.1), trisethoxydiglycol phosphate (SP value 18.1), lauryl alcohol (SP value 18.2), glyceryl monomyristate monoisostearate (SP value 18.4), oleyl alcohol (SP value 18.5), octyldodecyl lactate (SP value 18.5), 2-ethylhexyl paramethoxycinnamate (SP value 18.5), diisostearyl malate (SP value 18.5), tri glyceryl 2-ethylhexanoate (SP value 18.6), isopropyl myristate (SP value 18.6), diglyceryl diisostearate (SP value 18.7), polyglyceryl-2 diisostearate (SP value 19.0), 2-ethylhexyl 4-methoxycinnamate (SP value 19.0), glyceryl monomyristate monoisostearate (SP value 19.1), 2-ethylhexyl paramethoxycinnamate (SP value 19.2), diisostearic acid Polyglyceryl-10 (SP value 19.4), dl-α-tocopherol (SP value 19.4), ricinoleic acid (SP value 19.8) , methylphenylpolysiloxane (SP value 20.0), oleic acid monoglyceride (SP value 20.6), monoisostearyl glyceryl ether (SP value 20.6), sorbitan sesquioleate (SP value 20.9), mono Diglyceryl isostearate (SP value 21.7) and the like can be mentioned. Among them, isotridecyl isononanoate, neopentylglycol dicaprate, diisostearyl malate, isopropyl myristate, polyglyceryl-2 diisostearate, triisostearin, alkyl-1,3-dimethylbutyl ether, neopentyl glycol dicaprate, trisethoxydiglycol phosphate, 2-ethylhexyl para-methoxycinnamate, 2-ethylhexyl 4-methoxycinnamate, 2-Ethylhexyl paramethoxycinnamate is preferred, isotridecyl isononanoate, neopentyl glycol dicaprate, diisostearyl malate, isopropyl myristate, polyglyceryl-2 diisostearate, 2-ethylhexyl paramethoxycinnamate, 4-methoxycinnamate More preferred are 2-ethylhexyl para-methoxycinnamate and 2-ethylhexyl para-methoxycinnamate, and particularly preferred are isotridecyl isononanoate, neopentyl glycol dicaprate, diisostearyl malate, isopropyl myristate and polyglyceryl-2 diisostearate.

(isotridecyl isononanoate)
Isotridecyl isononanoate is an ester oil of isononanoic acid, which is a medium-chain branched fatty acid having 9 carbon atoms, and isotridecyl alcohol, which is a medium-chain branched alcohol, and has an SP value of 17.0. Also known as isotridecyl isononanoate. The isotridecyl isononanoate used in the present invention may be either liquid or solid at room temperature (20° C.) without any particular limitation. Oil agents that are liquid at room temperature are preferred from the viewpoint of obtaining a whitening effect. Commercial products can be used in the present invention.

(neopentyl glycol dicaprate)
Neopentyl glycol dicaprate is a diester made by ester-bonding two capric acids, which are medium-chain fatty acids and saturated fatty acids with 10 carbon atoms, to neopentyl glycol, a type of polyhydric alcohol, and has an SP value of 17. .7. The neopentyl glycol dicaprate used in the present invention may be either liquid or solid at room temperature (20° C.) without any particular limitation, but cannabidiol's skin absorption promoting action, cell activating action, anti-aging action, and improvement of rough skin. Oil agents that are liquid at room temperature are preferred from the viewpoint of obtaining action and whitening action. Commercial products can be used in the present invention.

(diisostearyl malate)
Diisostearyl malate is a diester (α- hydroxy acid ester), has an SP value of 18.5, and is also called distearyl malate. Diisostearyl malate may be liquid or solid at normal temperature (20° C.) and is not particularly limited, but cannabidiol has skin absorption promoting action, cell activating action, anti-aging action, rough skin improving action, and whitening action. From the viewpoint of obtaining the above, an oil that is liquid at room temperature is preferable. Commercial products can be used in the present invention.

(isopropyl myristate)
Isopropyl myristate is a fatty acid ester in which the hydroxy group (hydroxyl group) of isopropanol, which is a type of lower alcohol (monohydric alcohol), is bonded to the carboxyl group of myristic acid, which is a type of higher fatty acid, and has an SP value of 18. 6, also known as isopropyl myristate. The isopropyl myristate used in the present invention may be either liquid or solid at normal temperature (20° C.) without any particular limitation. Oil agents that are liquid at room temperature are preferred from the viewpoint of obtaining a whitening effect. Commercial products can be used in the present invention.

(Polyglyceryl-2 diisostearate)
Polyglyceryl-2 diisostearate has two isostearic acids, which are synthetic saturated fatty acids with 18 carbon atoms, as hydrophobic groups (lipophilic groups), and diglycerin, which is a type of polyhydric alcohol and has four hydroxyl groups, as hydrophilic groups. It is a diester with an SP value of 19.0 and is also called polyglyceryl diisostearate. The polyglyceryl-2 diisostearate used in the present invention may be either liquid or solid at room temperature (20° C.) without any particular limitation. Oil agents that are liquid at room temperature are preferred from the viewpoint of obtaining action and whitening action. Commercial products can be used in the present invention.

Only one of these oil agents (excluding hydrocarbon oil and silicone oil) may be used in the present invention, or two or more thereof may be used.

The content of the oil agent (excluding hydrocarbon oil and silicone oil) in the external preparation for skin of the present invention is not particularly limited, and is preferably 0.000001% by mass or more, more preferably 0.0001% by mass or more, It is particularly preferably 0.001% by mass or more from the viewpoint of obtaining percutaneous absorption promoting action, cell activating action, anti-aging action, rough skin improving action and whitening action of cannabidiol. Further, it is preferably 99.99% by mass or less, more preferably 95% by mass or less, and 90% by mass from the viewpoint of obtaining percutaneous absorption promoting action, cell activating action, anti-aging action, rough skin improving action, and whitening action of cannabidiol. The following are particularly preferred. When two or more oil agents (excluding hydrocarbon oil and silicone oil) are used, the content of the oil agent (excluding hydrocarbon oil and silicone oil) is the total amount.

The content of the oil (excluding hydrocarbon oil and silicone oil) relative to cannabidiol in the external preparation for skin of the present invention is not particularly limited. is preferred, more preferably 1:1 to 1,000,000, and particularly preferably 1:7.5 from the viewpoint of obtaining cannabidiol percutaneous absorption promoting action, cell activating action, anti-aging action, rough skin improving action, and whitening action. ~10000. When two or more oil agents (excluding hydrocarbon oils and silicone oils) are used, the content of the oil agents (excluding hydrocarbon oils and silicone oils) relative to cannabidiol is the total amount.

(c) Polyhydric alcohol The external preparation for skin of the present invention is characterized by containing cannabidiol and an oil (excluding hydrocarbon oil and silicone oil), and may further contain a polyhydric alcohol. A polyhydric alcohol used in the present invention is an organic compound having two or more hydroxy groups in one molecule. The polyhydric alcohol used in the present invention is not particularly limited as long as it is a polyhydric alcohol that can be used by applying it to the skin. For example, glycerin; dihydric alcohols such as 3-butylene glycol, 1,4-butylene glycol, propylene glycol, polyethylene glycol and 1,3-propanediol; sugar alcohols such as erythritol, maltitol, mannitol, sorbitol and xylitol; Sugars etc. can be mentioned. Among them, glycerin, diglycerin, ethylene glycol, 1,3-butylene glycol, and 1,4-butylene from the viewpoint of obtaining cannabidiol's skin absorption promoting action, cell activating action, anti-aging action, rough skin improving action, and whitening action. Glycol, propylene glycol, polyethylene glycol, 1,3-propanediol are preferred, and glycerin, diglycerin, ethylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, propylene glycol, polyethylene glycol, 1,3-propane. Diols are particularly preferred.

Only one of these polyhydric alcohols may be used in the present invention, or two or more thereof may be used.

The content of the polyhydric alcohol in the external preparation for skin of the present invention is not particularly limited, and is preferably 0.001% by mass or more, more preferably 0.01% by mass or more. It is particularly preferably 0.05% by mass or more from the viewpoint of obtaining an activating effect, an anti-aging effect, a rough skin improving effect, and a whitening effect. In addition, it is preferably 40% by mass or less, more preferably 30% by mass or less, and 20% by mass or less from the viewpoint of obtaining cannabidiol's percutaneous absorption promoting action, cell activation action, anti-aging action, rough skin improving action, and whitening action. Especially preferred. In addition, when using 2 or more types of polyhydric alcohols, content of a polyhydric alcohol is the total amount.

The content of polyhydric alcohol relative to cannabidiol in the external preparation for skin of the present invention is not particularly limited, and when the content of cannabidiol is 1, it is preferably 1:0.001 to 10,000,000, more preferably 1:0. 01 to 100,000, and particularly preferably 1:0.05 to 10,000 from the viewpoint of obtaining percutaneous absorption promoting action, cell activating action, anti-aging action, rough skin improving action and whitening action of cannabidiol.

(d) Alkylene oxide adducts of glycerin and/or diglycerin The external preparation for skin of the present invention is characterized by containing cannabidiol and an oil agent (excluding hydrocarbon oil and silicone oil), and further glycerin and/or Alkylene oxide adducts of diglycerin can be included. The alkylene oxide addition derivative of glycerin and/or diglycerin used in the present invention is not particularly limited as long as it is a component that can be used by applying to the skin. 8/5/3 glycerin, polyoxybutylene polyoxyethylene polyoxypropylene glyceryl ether, and the like. Among them, PPG-9 diglyceryl, PEG/PPG/polybutylene glycol-8/5/3 glycerin from the viewpoint of obtaining cannabidiol's skin absorption promoting action, cell activation action, anti-aging action, rough skin improvement action, and whitening action. is preferred.

The alkylene oxide addition derivatives of glycerin and/or diglycerin used in the present invention may be used alone or in combination of two or more thereof.

The content of the alkylene oxide adduct of glycerin and/or diglycerin in the external preparation for skin of the present invention is not particularly limited, and is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, and cannabidiol. From the viewpoint of obtaining percutaneous absorption promoting action, cell activating action, anti-aging action, rough skin improving action and whitening action, it is particularly preferably 0.01% by mass or more. Also, it is preferably 15% by mass or less, more preferably 12.5% by mass or less, and 10% by mass from the viewpoint of obtaining cannabidiol percutaneous absorption promoting action, cell activation action, anti-aging action, rough skin improving action, and whitening action. The following are particularly preferred. When two or more alkylene oxide addition derivatives of glycerin and/or diglycerin are used, the content of the alkylene oxide addition derivatives of glycerin and/or diglycerin is the total amount.

The content of the alkylene oxide addition derivative of glycerin and/or diglycerin to cannabidiol in the external preparation for skin of the present invention is not particularly limited, and is preferably 1:0.05 to 100000000 when the content of cannabidiol is 1. , more preferably 1:0.07 to 1000000, and particularly preferably 1:0.09 from the viewpoint of obtaining percutaneous absorption promoting action, cell activating action, anti-aging action, rough skin improving action and whitening action of cannabidiol ~10000.

The dosage form of the external preparation for skin of the present invention includes water-based, oil-based, emulsified (water-in-oil, oil-in-water, etc.), solubilized, powder-based, and solvent-based forms. However, from the viewpoint of cannabidiol's skin absorption promoting action, cell activation action, anti-aging action, rough skin improvement action, whitening action, ease of application, and formulation properties, it is water-based, oil-based, emulsified, and solubilized. More preferably, it is an emulsifying system, that is, an emulsion. When the skin preparation for external use of the present invention is an emulsion, the emulsified form of the skin preparation for external use of the present invention can be appropriately changed according to the shape to be used. It can take any form of oil-in-water type, but it should be an oil-in-water emulsion from the viewpoint of cannabidiol's skin absorption promoting action, cell activating action, anti-aging action, rough skin improving action, whitening action, and ease of application. is preferred.

The external preparation for skin of the present invention is a composition that is applied to the skin and used, and is not particularly limited as long as it is applied to the skin and used as, for example, cosmetics, pharmaceuticals, and quasi-drugs. When the skin preparation for external use of the present invention is a cosmetic or quasi-drug, examples include lotions, beauty essences, beauty creams, milky lotions, all-in-one gels, packs, cleansers, soaps, and ointments. Lotions, beauty essences, creams, all-in-one gels, milky lotions, cleansers or soaps are preferred from the viewpoints of promoting action, cell activating action, anti-aging action, rough skin improving action, whitening action, and ease of use. Serums, creams, milky lotions and detergents are more preferred, and creams and milky lotions are particularly preferred.

The external preparation for skin of the present invention exhibits the effect of the present invention in addition to the above cannabidiol, oil agent (excluding hydrocarbon oil and silicone oil), polyhydric alcohol, glycerin and/or alkylene oxide adduct of diglycerin. Various active ingredients, pH adjusters, thickeners, fragrances, colorants, antioxidants, antibacterial and antifungal agents, hydrocarbon oils, silicone oils, alcohols (however, polyhydric alcohols ), inorganic salts, lubricants, solvents, and other ingredients that are usually used in external preparations for skin can be blended.

Hereinafter, the components contained in the external preparation for skin according to the present invention, which are cannabidiol, oils (excluding hydrocarbon oils and silicone oils), polyhydric alcohols, glycerin and/or diglycerin alkylene oxide adducts. A representative example other than the above will be further described.

The active ingredient used in the present invention is not particularly limited, and drugs used in cosmetics, pharmaceuticals, quasi-drugs, etc., plant extracts, etc. can be used depending on the purpose. Typical examples include glycyrrhizic acid or derivatives thereof, whitening agents such as placenta extract, and plant components such as licorice. In addition, as plant components, whole plants, leaves (leaf blades, petioles, etc.), fruits (mature, immature, etc.), seeds, flowers (petals, ovaries, etc.), stems, rhizomes, roots, tuberous roots, etc. may be dried or dried. Although it can be used in the form of powder, it is common to use an extract extracted by a conventional method using a solvent such as water, ethanol, or polyhydric alcohol.

The external preparation for skin according to the present invention is excellent in percutaneous absorbability of cannabidiol, and is a cosmetic or pharmaceutical intended for cell activation, anti-aging, improvement of rough skin, whitening, etc., by allowing cannabidiol to be absorbed into the skin. , Can be used as a quasi-drug. When the external skin preparation of the present invention is used as cosmetics, pharmaceuticals, or quasi-drugs, it can be used by putting it in a container suitable for storage and use. Examples of the container include plastic, glass, metal, and the like, and are not particularly limited. However, from the viewpoint of maintaining the stability of cannabidiol and preservability, and maintaining and improving the action and effect of cannabidiol, light-shielding properties are preferred. A container with

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the scope of the present invention is not limited to these Examples.

<Preparation of topical skin preparation>
According to the composition shown in Table 1, an external preparation for skin of the present invention was prepared.
As cannabidiol, CBD powder (CBD content of 98.0% or more) purified from natural products was used.
The ester oils include isotridecyl isononanoate, which has an SP value of 17.0 and is liquid at normal temperature (20°C), and diisostearyl malate, which has an SP value of 18.5 and is liquid at normal temperature (20°C), and has an SP value of 18.6. Isopropyl myristate, which is liquid at room temperature (20° C.), and polyglyceryl-2 diisostearate, which has an SP value of 19.0 and is liquid at room temperature (20° C.), were used.
Squalane with an SP value of 16.2 and mineral oil with an SP value of 22.5 were used as hydrocarbon oils.
As a control, DPG, which is a polyhydric alcohol and has an SP value of 27.5, was used.

<Confirmation test of percutaneous absorption promotion effect>
A bandage for a patch test with an 8 mm square hole was applied to the upper arm of the panelists (3 persons), and then 30 μL of the sample was applied. One hour after the application, the bandage was removed, and then the applied area was tape-stripped five times with cellophane tape, and the amount of cannabidiol in the stratum corneum adhering to the cellophane tape was measured. Cannabidiol was quantified by liquid chromatography of ethanol extracts from each of the five cellophane tapes. The solubility of cannabidiol and oil dissolved in ethanol was confirmed and evaluated according to the following solubility criteria. After that, the percutaneous absorbability was determined by the following formula and judged according to the percutaneous absorbability criteria below.

Criteria for determining the solubility of cannabidiol and oils in ethanol

Percutaneous absorption rate X: Amount of cannabidiol in the stratum corneum adhered to the 4th and 5th cellophane tapes (total of 3 people)
Y: Amount of cannabidiol in the stratum corneum adhered to the second and third cellophane tapes (total of 3 people)
Percutaneous absorption rate (%) = (X/Y) x 100

Criteria for determination of percutaneous absorbability ○: Cannabidiol and oil are completely dissolved, percutaneous absorption rate is 10% or more △: Cannabidiol and oil are completely dissolved, percutaneous absorption rate is 0% or more and less than 10% × : Cannot be determined because cannabidiol and oil are not completely dissolved

Table 2 shows the results. From the results in Table 2, when cannabidiol and an ester oil with an SP value of 16.5 to 22.0 were contained, cannabidiol and a hydrocarbon oil or silicone oil with an SP value of less than 17 or more than 21 were contained. The percutaneous absorption rate was higher than in the case. Therefore, it was found that the percutaneous absorption enhancer according to the present invention is excellent in the effect of promoting the absorption of cannabidiol into the skin.

As is clear from the above test results, the present invention can provide an external preparation for skin in which the permeability of cannabidiol to the skin is enhanced.

<Production Examples 1 to 8>
According to the compositions shown in Tables 3 and 4 below, external preparations for skin that are oil-in-water emulsions were produced. Specifically, at a predetermined temperature, an aqueous phase component and an oil phase component were prepared and emulsified. The external preparations for skin obtained in the following production examples have a high cannabidiol percutaneous absorption promotion effect, and are excellent in cell activating effect, anti-aging effect, rough skin ameliorating effect, whitening effect and cell activating effect.

<Production Examples 9 to 14>
Creams, which are oil-in-water emulsions, were produced according to the compositions shown in Tables 5 and 6 below. Specifically, the following cream was obtained by adding the dissolved oil phase while stirring the aqueous phase and stirring until uniform. The external preparations for skin obtained in the following production examples have a high cannabidiol percutaneous absorption promotion effect, and are excellent in cell activating effect, anti-aging effect, rough skin ameliorating effect, whitening effect and cell activating effect.

Claims (9)

An external skin preparation comprising (a) cannabidiol and (b) an oil agent (excluding hydrocarbon oil and silicone oil). 2. The external preparation for skin according to claim 1, wherein the component (b) is at least one selected from ester oils and fats and oils. The (b) component is an ester oil comprising a fatty acid having 8 to 24 carbon atoms and an aliphatic alcohol having 3 to 24 carbon atoms, an ester oil comprising a polyhydric alcohol having 2 or more carbon atoms and a fatty acid having 8 to 24 carbon atoms, and 3. The external preparation for skin according to claim 2, which is at least one kind selected from ester oils consisting of dicarboxylic acids and aliphatic alcohols having 3 to 18 carbon atoms. 4. The external preparation for skin according to any one of claims 1 to 3, wherein component (b) is an oil having a solubility parameter (SP value) of 16.5 to 22.0. (b) Component is at least one selected from isotridecyl isononanoate, neopentyl glycol dicaprate, diisostearyl malate, isopropyl myristate, and polyglyceryl-2 diisostearate. The skin external preparation according to any one of the above. 6. The external preparation for skin according to any one of claims 1 to 5, further comprising (c) a polyhydric alcohol. 7. The external preparation for skin according to any one of claims 1 to 6, further comprising (d) an alkylene oxide addition derivative of glycerin and/or diglycerin. 8. The external preparation for skin according to any one of claims 1 to 7, which is an emulsion. 9. The external preparation for skin according to claim 8, which is an oil-in-water emulsion.