Topical skin preparations

Abstract

To provide an external preparation for skin which increases the permeability of cannabidiol into the skin and has excellent solubility by incorporating (a) cannabidiol and (b) a nonionic surfactant after finding an external preparation for skin having a percutaneous absorption promoting action of cannabidiol and excellent solubility.SOLUTION: There is provided an external preparation for skin which contains (a) cannabidiol and (b) a nonionic surfactant in which the permeability of cannabidiol into the skin is increased by blending a surfactant as a percutaneous absorption enhancer of cannabidiol. In addition, the solubility of cannabidiol can be enhanced by blending a nonionic surfactant as a raw material to improve the solubility of cannabidiol.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a topical skin preparation containing cannabidiol and a nonionic surfactant. Specifically, it relates to a topical skin preparation excellent in solubility, characterized by enhancing the permeability of cannabidiol into the skin. More specifically, in a topical skin preparation characterized by containing cannabidiol and a nonionic surfactant, it relates to a topical skin preparation characterized by formulating a nonionic surfactant for the purpose of enhancing the solubility of cannabidiol and the permeability of cannabidiol into the skin.

Background Art

[0002] Cannabidiol (CBD) has attracted attention as a component with expected new pharmacological effects. Cannabidiol is one of the cannabinoids contained in hemp, and for example, therapeutic agents for epilepsy and therapeutic compositions for tuberous sclerosis have been developed (Patent Documents 1 and 2). In addition, its use as a topical preparation has also been developed.

[0003] However, since cannabidiol is a highly lipophilic compound, its permeability into the skin is low, and it is difficult to be absorbed from membranes such as the skin. Therefore, a topical skin preparation with improved transdermal absorption of cannabidiol is desired.

[0004] Conventionally, in the beauty industry and the like, topical skin preparations such as liquid, gel, jelly, powder, semi-solid, and solid forms have been manufactured. However, for liquid, gel, and jelly topical skin preparations, the solubility is poor, and raw materials may remain undissolved. Furthermore, due to poor solubility, there are drawbacks such that beauty raw materials and medicinal effect raw materials cannot be fully exerted, and when applied to the skin, it may cause a rough feeling or an unpleasant feeling of use. Also, for powder topical skin preparations, when water is blended or dissolved in water, the solubility is poor, raw materials may remain undissolved, or it may take a long time to completely dissolve. Furthermore, due to poor solubility, there is also a drawback that beauty raw materials and medicinal effect raw materials cannot be fully exerted.

[0005] Therefore, methods have been proposed to improve the solubility of topical skin preparations by combining specific raw materials or by using specific manufacturing methods. For example, a known preparation contains a powder obtained by mixing L-ascorbic acid phosphate magnesium salt, a type of vitamin C derivative, with cyclodextrin, a type of polysaccharide, and then drying the mixture (Patent Document 3).

[0006] However, many conventional topical skin preparations lack sufficient solubility. Therefore, there is a need for topical skin preparations with improved solubility. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Special Publication No. 2013-523708 [Patent Document 2] Special Publication No. 2017-537064 [Patent Document 3] Japanese Patent Publication No. 2004-315429 [Overview of the Initiative] [Problems that the invention aims to solve]

[0008] Therefore, the present invention aims to provide an excellent topical skin preparation that enhances the solubility of cannabidiol and the absorption effect of cannabidiol into the skin and mucous membranes. [Means for solving the problem]

[0009] The present inventors conducted studies on the solubility and transdermal absorption of cannabidiol in various substances in order to find a topical skin preparation containing cannabidiol that is excellent in terms of cannabidiol solubility and transdermal absorption-promoting effect. As a result, they found an improvement in cannabidiol solubility and a transdermal absorption-promoting effect, leading to the completion of the present invention. That is, the present invention relates to a topical skin preparation characterized by containing cannabidiol and a nonionic surfactant. Furthermore, the present invention relates to a topical skin preparation characterized by containing cannabidiol and a nonionic surfactant, wherein the substance that improves the solubility and promotes the transdermal absorption of cannabidiol is the nonionic surfactant.

[0010] The outline of the present invention is as follows: [1] A topical skin preparation characterized by containing (a) cannabidiol and (b) a nonionic surfactant. [2](b) The topical skin preparation according to [1], characterized in that component (b) is a nonionic surfactant with an HLB value greater than 9.7. [3](b) The topical skin preparation according to either [1] or [2], characterized in that component (b) is a nonionic surfactant with an HLB value greater than 10.5. [4](b) A topical skin preparation according to any one of [1] to [3], characterized in that component (b) is a nonionic surfactant with an HLB value of 13.0 or higher. [5](b) A topical skin preparation according to any one of [1] to [4], characterized in that component (b) is a nonionic surfactant with an HLB value of 13.0 or more and less than 17.5. [6](b) A topical skin preparation according to any one of [1] to [5], characterized in that the component is soluble in water. [7](b) The topical skin preparation according to any one of [1] to [6], characterized in that component is at least one selected from fatty acid polyoxyethylene glyceryl, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, fatty acid polyoxyethylene sorbitan, and polyoxyethylene fatty acid ester. [8](b) A topical skin preparation according to any one of [1] to [7], characterized in that the component is at least one selected from PEG-20 glyceryl isostearate, PEG-60 hydrogenated castor oil, laureth-9, polysorbate 60, and PEG-40 stearate. [9](b) A topical skin preparation according to any one of [1] to [8], characterized in that the component is at least one selected from PEG-20 glyceryl isostearate, PEG-60 hydrogenated castor oil, laureth-9, and polysorbate 60.

[10] A topical skin preparation according to any one of [1] to [9], characterized in that the topical skin preparation is at least one selected from lotion, serum, cream, emulsion, all-in-one gel, pack, cleanser and soap.

[11] Furthermore, the topical skin preparation according to any one of [1] to

[10] , characterized in that it contains (c) an oil. [Effects of the Invention]

[0011] According to the present invention, it is possible to provide a topical skin preparation that has excellent solubility of cannabidiol and enhanced skin permeability. In particular, in a topical skin preparation containing cannabidiol and a nonionic surfactant, the solubility and skin permeability of cannabidiol can be enhanced by incorporating the nonionic surfactant to improve the solubility of cannabidiol and as a skin absorption enhancer. Furthermore, according to the present invention, in a topical skin preparation selected from lotions, serums, creams, emulsions, all-in-one gels, packs, cleansers, and soaps containing cannabidiol and a nonionic surfactant, the solubility and skin permeability of cannabidiol can be enhanced by incorporating the nonionic surfactant to improve the solubility of cannabidiol and as a skin absorption enhancer. [Brief explanation of the drawing]

[0012] [Figure 1] This figure shows the transdermal absorption rate of the topical skin preparation of the present invention (containing cannabidiol and a nonionic surfactant). [Modes for carrying out the invention]

[0013] The present invention relates to a topical skin preparation characterized by containing cannabidiol and a nonionic surfactant, wherein the surfactant has the effect of improving the solubility of cannabidiol and promoting skin absorption.

[0014] (a) Cannabidiol The topical skin preparation of the present invention is characterized by containing cannabidiol. Cannabidiol is a type of cannabinoid and is known to be found in hemp. Cannabidiol is known to have different pharmacological effects from tetrahydrocannabinol, which is also a type of cannabinoid. In the present invention, cannabidiol can be extracted and purified from plants such as hemp or citrus peels, or synthesized, but it is preferable to use cannabidiol that has been purified from natural products or synthesized from natural products in order to enhance safety and the high cell-activating, anti-aging, skin-improving, and whitening effects of cannabidiol.

[0015] The cannabidiol content in the topical skin preparation of the present invention is not particularly limited, but is preferably 0.000001% by mass or more, more preferably 0.00001% by mass or more, and particularly preferably 0.001% by mass or more from the viewpoint of obtaining high cell activation, anti-aging, skin roughness improvement, and whitening effects. Furthermore, 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 activation, anti-aging, skin roughness improvement, and whitening effects.

[0016] (b) Nonionic surfactants The external preparation for skin of the present invention is characterized by containing a nonionic surfactant together with cannabidiol. The nonionic surfactant used in the present invention may be any surfactant that can be applied to the skin, and it may be a liquid or a solid such as powder, fine granule, granule, flake, solid form, etc., without particular limitation. From the viewpoints of improving solubility, storage stability, ease of handling, and promoting the skin absorption of cannabidiol, those that can be uniformly dissolved in water at room temperature (20°C) are preferable.

[0017] The HLB value of the nonionic surfactant used in the present invention is not particularly limited. From the viewpoints of promoting the skin absorption of cannabidiol, cell activation effect, anti-aging effect, improving rough skin, whitening effect, improving solubility, storage stability, and ease of handling, it is preferably greater than 9.7, more preferably greater than 10.5, still more preferably 13.0 or more, and particularly preferably 13.0 or more and less than 17.5. The HLB value is an index indicating the hydrophilic-lipophilic balance (Hydrophilic-Lypophilic Balance), and indicates the molecular weight of the hydrophilic group portion in the total molecular weight of the surfactant, and is obtained, for example, by Griffin's formula.

[0018] Examples of nonionic surfactants having an HLB value greater than 9.7 include glyceryl PEG-20 isostearate, PEG-60 hydrogenated castor oil, laureth-9, polysorbate 60, PEG-40 stearate, polyoxyethylene (12) lauryl ether, polyoxyethylene (14) lauryl ether, and polyoxyethylene tridecyl ether. Among these, from the viewpoints of promoting the skin absorption of cannabidiol, cell activation effect, anti-aging effect, improving rough skin, whitening effect, and improving solubility, glyceryl PEG-20 isostearate, PEG-60 hydrogenated castor oil, laureth-9, polysorbate 60, and PEG-40 stearate are preferable, and glyceryl PEG-20 isostearate, PEG-60 hydrogenated castor oil, laureth-9, and polysorbate 60 having an HLB value of 13.0 to less than 17.5 are particularly preferable.

[0019] When two or more nonionic surfactants are used in the present invention, the HLB value is the weighted average of the HLB values of each nonionic surfactant based on its blending ratio. Therefore, even if the HLB value of an individual nonionic surfactant is 9.7 or less, or greater than 17.5, as long as the mixed HLB value is greater than 9.7 and 17.5 or less, it is a nonionic surfactant with an HLB value greater than 9.7 and 17.5 or less in the present invention.

[0020] As the nonionic surfactant, any nonionic surfactant such as ester type, ether type, ester-ether type, polyethylene glycol type, alkyl polyglycoside, etc. may be used without particular limitation. From the viewpoints of solubility, storage stability, ease of handling, and the effect of promoting the skin absorption of cannabidiol, ester type, ether type, and ester-ether type are preferred, and ether type and ester-ether type are particularly preferred. Incidentally, ether type and ester-ether type nonionic surfactants are also collectively called polyethylene glycol type when these two are combined.

[0021] Examples of ether-type nonionic surfactants, which are a type of polyethylene glycol surfactant, include polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, polyoxyethylene polyhydric alcohol fatty acid esters, and polyoxyethylene sorbitan fatty acid esters. Among these, PEG-20 glyceryl isostearate, laureth-9, polysorbate 60, PEG-40 stearate, polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, polyoxyethylene oleyl ether, polyoxyethylene behenyl ether, polyoxyethylene polyoxypropylene cetyl ether, and polyoxyethylene polyoxypropylene decyltetradecyl ether are preferred, and PEG-20 glyceryl isostearate, laureth-9, polysorbate 60, and PEG-40 stearate are particularly preferred from the viewpoint of improving solubility, storage stability, ease of handling, and promoting skin absorption of cannabidiol.

[0022] Examples of ester-ether type nonionic surfactants, which are a type of polyethylene glycol, include PEG-60 hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene oleate ester, polyoxyethylene distearate ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene coconut oil fatty acid sorbitan, polyoxyethylene glyceryl oleate, and polyoxyethylene glyceryl isostearate. Among these, polyoxyethylene oleate ester, polyoxyethylene hydrogenated castor oil, and polyoxyethylene coconut oil fatty acid sorbitan are particularly preferred in terms of dispersibility in water, and PEG-60 hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, and polyoxyethylene coconut oil fatty acid sorbitan are preferred in terms of solubility improvement, storage stability, ease of handling, and cannabidiol skin absorption promotion, with PEG-60 hydrogenated castor oil being particularly preferred.

[0023] • Fatty acid polyoxyethylene glyceryl Fatty acid polyoxyethylene glyceryl is a nonionic surfactant obtained from fatty acids, glycerin (a type of polyhydric alcohol), and ethylene oxide, and is classified as an ethylene oxide condensation type polyoxyethylene polyhydric alcohol fatty acid ester.

[0024] (PEG-20 glyceryl isostearate) PEG-20 glyceryl isostearate is a type of fatty acid polyoxyethylene glyceryl, obtained from isostearic acid, a branched saturated fatty acid with 18 carbon atoms, glycerin, a type of polyhydric alcohol, and ethylene oxide (totaling about 20 moles). It is a nonionic surfactant classified as an ethylene oxide condensation type polyoxyethylene polyhydric alcohol fatty acid ester. PEG-20 glyceryl isostearate is solid, liquid, or paste-like at room temperature (20°C), has an HLB value of 13.0, and is also called polyoxyethylene glyceryl isostearate. The PEG-20 glyceryl isostearate used in this invention may be solid, liquid, or paste-like at room temperature (20°C) and is not particularly limited. However, from the viewpoint of improving solubility, storage stability, ease of handling, and promoting skin absorption of cannabidiol, it is preferable that it dissolves uniformly in water at room temperature (20°C). Commercially available PEG-20 glyceryl isostearate can be used in this invention.

[0025] (PEG-60 Hydrogenated Castor Oil) PEG-60 hydrogenated castor oil is a type of fatty acid polyoxyethylene glyceryl, and is a mixture of ethers and esters obtained by addition polymerization of ethylene oxide (about 60 moles) to fatty acids and triglycerides obtained from hydrogenated castor oil. It is a nonionic surfactant classified as ethylene oxide condensation type polyoxyethylene hydrogenated castor oil. PEG-60 hydrogenated castor oil is solid, liquid, or paste-like at room temperature (20°C), has an HLB value of 14.0, and is also called polyoxyethylene hydrogenated castor oil. PEG-60 hydrogenated castor oil may be solid, liquid, or paste-like at room temperature (20°C) and is not particularly limited in its state. However, from the viewpoint of improving solubility, storage stability, ease of handling, and promoting skin absorption of cannabidiol, it is preferable that it dissolves uniformly in water at room temperature (20°C). Commercially available PEG-60 hydrogenated castor oil can be used in this invention.

[0026] • Polyoxyethylene alkyl ether Polyoxyethylene alkyl ethers are ethers obtained by etherically bonding ethylene oxide to a higher alcohol, and are nonionic surfactants classified as ethylene oxide condensation type polyoxyethylene alkyl ethers.

[0027] (Laures-9) Laureth-9 is a type of polyoxyethylene alkyl ether, obtained by etherically bonding ethylene oxide (approximately 9 moles) to lauryl alcohol, a higher alcohol with 12 carbon atoms. It is a nonionic surfactant classified as an ethylene oxide condensation type polyoxyethylene alkyl ether. Laureth-9 is solid, liquid, or paste-like at room temperature (20°C), has an HLB value of 14.5, and is also called polyoxyethylene lauryl ether. Laureth-9 can be solid, liquid, or paste-like at room temperature (20°C) and is not particularly limited, but it is preferable that it dissolves uniformly in water at room temperature (20°C) from the viewpoint of improving solubility, storage stability, ease of handling, and promoting skin absorption of cannabidiol. Commercially available laureth-9 can be used in this invention.

[0028] • Fatty acid polyoxyethylene sorbitan Fatty acid polyoxyethylene sorbitan is a nonionic surfactant classified as an ethylene oxide condensation type polyoxyethylene sorbitan fatty acid ester, obtained by addition polymerization of ethylene oxide to sorbitan fatty acid ester.

[0029] (Polysorbate 60) Polysorbate 60 is a type of fatty acid polyoxyethylene sorbitan, and is a nonionic surfactant classified as an ethylene oxide condensation type polyoxyethylene sorbitan fatty acid ester, obtained by addition polymerization of ethylene oxide (about 20 moles) to sorbitan stearate, which is a type of sorbitan fatty acid ester. At room temperature (20°C), polysorbate 60 is solid, liquid, or paste-like, has an HLB value of 14.9, and is also called polyoxyethylene sorbitan monostearate. Polysorbate 60 may be solid, liquid, or paste-like at room temperature (20°C) and is not particularly limited in its state, but it is preferable that it dissolves uniformly in water at room temperature (20°C) from the viewpoint of improving solubility, storage stability, ease of handling, and promoting skin absorption of cannabidiol. Commercially available polysorbate 60 can be used in this invention.

[0030] • Polyoxyethylene fatty acid esters Polyoxyethylene fatty acid esters are monoesters obtained by esterifying ethylene oxide to higher fatty acids, and are nonionic surfactants classified as ethylene oxide condensation type polyoxyethylene fatty acid esters.

[0031] (PEG-40 stearate) PEG-40 stearate is a type of polyoxyethylene fatty acid ester, a monoester obtained by esterifying ethylene oxide (approximately 40 moles) with stearic acid, a higher fatty acid with 18 carbon atoms. It is a nonionic surfactant classified as an ethylene oxide condensation type polyoxyethylene fatty acid ester. PEG-40 stearate is solid, liquid, or paste-like at room temperature (20°C), has an HLB value of 17.5, and is also called polyethylene glycol monostearate or polyethylene glycol monostearate (40E.0). PEG-40 stearate can be solid, liquid, or paste-like at room temperature (20°C) and is not particularly limited in its state. However, from the viewpoint of improving solubility, storage stability, ease of handling, and promoting skin absorption of cannabidiol, it is preferable that it dissolves uniformly in water at room temperature (20°C). Commercially available PEG-40 stearate can be used in this invention.

[0032] In this invention, only one of these nonionic surfactants may be used, or two or more may be used.

[0033] The content of the nonionic surfactant in the topical skin preparation of the present invention is not particularly limited, but is preferably 0.000005% by mass or more, more preferably 0.0001% by mass or more, and is particularly preferred at 0.00005% by mass or more from the viewpoint of obtaining solubility-enhancing effects, transdermal absorption-promoting effects of cannabidiol, cell-activating effects, anti-aging effects, skin roughness-improving effects, and whitening effects. Furthermore, is preferably 60% by mass or less, more preferably 50% by mass or less, and is particularly preferred at 40% by mass or less from the viewpoint of obtaining solubility-enhancing effects, transdermal absorption-promoting effects of cannabidiol, cell-activating effects, anti-aging effects, skin roughness-improving effects, and whitening effects. When two or more surfactants are used, the surfactant content is the total amount.

[0034] The content of nonionic surfactant relative to cannabidiol in the topical skin preparation of the present invention is not particularly limited. When the cannabidiol content is set to 1, a ratio of 1:0.005 to 1,000,000 is preferred, and more preferably 1:0.01 to 500,000. From the viewpoint of obtaining solubility-enhancing effects, transdermal absorption-promoting effects of cannabidiol, cell-activating effects, anti-aging effects, skin roughness-improving effects, and whitening effects, a ratio of 1:0.02 to 1,000,000 is particularly preferred. When two or more nonionic surfactants are used, the content of the surfactants relative to cannabidiol is the total amount.

[0035] The topical skin preparation of the present invention may contain surfactants other than nonionic surfactants in addition to nonionic surfactants. Examples of surfactants other than nonionic surfactants include anionic surfactants, cationic surfactants, and amphoteric surfactants.

[0036] (c) Oils The topical skin preparation of the present invention is characterized by containing cannabidiol and a nonionic surfactant, and may further contain an oil. The oil used in the present invention may be any oil that can be applied to the skin, and can be either polar or nonpolar. Furthermore, it may be solid or liquid at room temperature (20°C) and is not particularly limited, but a liquid oil at room temperature (20°C) is preferred from the viewpoint of obtaining solubility-enhancing effects, effects of promoting skin absorption of cannabidiol, cell activation effects, anti-aging effects, skin roughness improvement effects, and whitening effects.

[0037] Examples of oils used in the present invention include hydrocarbons, higher fatty acids, higher alcohols, waxes, fats and oils, ester oils, and silicones. Examples of hydrocarbon oils include petrolatum. Examples of higher fatty acid oils include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and linoleic acid. Examples of higher alcohol oils include stearyl alcohol, behenyl alcohol, and cetanol. Examples of waxes include jojoba seed oil, and animal-derived beeswax and lanolin. Examples of fats and oils include olive fruit oil, coconut oil, shea butter, and horse oil. Examples of ester oils include cetyl ethylhexanoate and triethylhexanoin. Examples of silicone oils include dimethicone, cyclopentasiloxane, and methylphenylsiloxane. Among these, hydrocarbons, higher fatty acids, higher alcohols, oils and fats, ester oils and silicones are preferred from the viewpoint of obtaining solubility-enhancing effects, cannabidiol-promoting skin absorption effects, cell-activating effects, anti-aging effects, skin roughness-improving effects and whitening effects, with higher fatty acids, higher alcohols, oils and fats and ester oils being particularly preferred.

[0038] The oil agents used in this invention may be of one type only, or two or more types may be used.

[0039] When the topical skin preparation of the present invention contains an oil, the oil content is not particularly limited, but is preferably 0.000009% by mass or more, more preferably 0.00001% by mass or more, and is particularly preferred at 0.00009% by mass or more from the viewpoint of obtaining solubility-enhancing effects, transdermal absorption-promoting effects of cannabidiol, cell-activating effects, anti-aging effects, skin roughness-improving effects, and whitening effects. Furthermore, is preferably 99.999% by mass or less, more preferably 99.99% by mass or less, and is particularly preferred at 99.9% by mass or less from the viewpoint of obtaining solubility-enhancing effects, transdermal absorption-promoting effects of cannabidiol, cell-activating effects, anti-aging effects, skin roughness-improving effects, and whitening effects. When two or more types of oils are used, the oil content is the total amount of those oils.

[0040] The oil content relative to cannabidiol in the topical skin preparation of the present invention is not particularly limited. When the cannabidiol content is set to 1, a ratio of 1:1 to 1:999999 is preferred, more preferably 1:5 to 1:99999, and particularly preferred from the viewpoint of obtaining solubility-enhancing effects, transdermal absorption-promoting effects of cannabidiol, cell-activating effects, anti-aging effects, skin roughness-improving effects, and whitening effects.

[0041] The dosage form of the topical skin preparation of the present invention can be water-based, oil-based, emulsion-based (water-in-oil, oil-in-water, etc.), solubilized, powder-based, solvent-based, etc., and is not particularly limited. However, from the viewpoint of promoting skin absorption of cannabidiol, cell activation, anti-aging, skin roughness improvement, whitening, solubility improvement, ease of application, and formulation properties, water-based, oil-based, emulsion-based, and solubilized systems are preferred. When the topical skin preparation of the present invention is an emulsion, i.e., an emulsion, the emulsion form of the topical skin preparation of the present invention can be appropriately changed according to the form used, and can take any of the following forms: oil-in-water, water-in-oil, water-in-oil-in-water, or oil-in-water. However, from the viewpoint of promoting skin absorption of cannabidiol, cell activation, anti-aging, skin roughness improvement, whitening, solubility improvement, and ease of application, oil-in-water emulsions are preferred.

[0042] The topical skin preparation of the present invention is a composition used by applying it to the skin, and there are no particular limitations as long as it is a topical preparation used by applying it to the skin, for example, it can be used as a cosmetic, pharmaceutical, or quasi-drug. When the topical skin preparation of the present invention is a cosmetic or quasi-drug, examples include lotions, serums, creams, emulsions, all-in-one gels, packs, cleansers, soaps, and ointments, but from the viewpoint of promoting skin absorption of cannabidiol, cell activation, anti-aging, skin roughness improvement, whitening, solubility improvement, and ease of use, it is preferable to be a lotion, serum, cream, emulsion, all-in-one gel, pack, cleanser, or soap, and it is particularly preferable to be a lotion, serum, cream, emulsion, or all-in-one gel.

[0043] In addition to cannabidiol, nonionic surfactants, and oils, the topical skin preparation of the present invention may contain various active ingredients, pH adjusters, thickeners, lubricants, antioxidants, preservatives, antibacterial and antifungal agents, fragrances, colorants, alcohols, inorganic salts, solvents, surfactants other than nonionic surfactants, and other ingredients commonly used in topical skin preparations, as long as they do not impair the effects of the present invention.

[0044] The active ingredients used in this invention are not particularly limited, and drugs and plant extracts used in cosmetics, pharmaceuticals, quasi-drugs, etc., can be used as appropriate. Typical examples include whitening agents such as arbutin, kojic acid, and vitamin C derivatives, and plant components such as licorice and saxifrage. As for plant components, the whole plant, leaves (leaf blade, petiole, etc.), fruits (mature, immature, etc.), seeds, flowers (petals, ovary, etc.), stems, rhizomes, roots, tubers, etc. can be used after drying or powdering, but it is common to use extracts obtained by conventional methods using solvents such as water, ethanol, and polyhydric alcohols.

[0045] The topical skin preparation according to the present invention exhibits excellent transdermal absorption of cannabidiol, and by allowing cannabidiol to be absorbed into the skin, it can be used as a cosmetic, pharmaceutical, or quasi-drug for purposes such as cell activation, anti-aging, improvement of rough skin, and whitening. When using the topical skin preparation of the present invention as a cosmetic, pharmaceutical, or quasi-drug, it can be used in a container suitable for storage and use. Examples of containers include plastic, glass, and metal, and are not particularly limited, but a light-shielding container is preferred from the viewpoint of maintaining the stability and shelf life of cannabidiol, and maintaining and improving the action and effects of cannabidiol. [Examples]

[0046] 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.

[0047] [Test 1: Solubility Test] The topical skin preparation of the present invention was prepared according to the composition shown in Table 1. For the cannabidiol, we used synthetically obtained CBD powder (CBD content of 98.0% or higher). As nonionic surfactants, PEG-20 glyceryl isostearate (HLB value 13.0, liquid), PEG-60 hydrogenated castor oil (HLB value 14.0, liquid), laureth-9 (HLB value 14.5, liquid), polysorbate 60 (HLB value 14.9, liquid), and PEG-40 stearate (HLB value 17.5, solid) were used. As controls, the anionic surfactants TEA cocoyl glutamate (liquid), potassium cocoyl glycinate (liquid), and sodium lauroyl methylalanine (liquid), and the amphoteric surfactants cocamidopropyl betaine (liquid), lauramidopropyl hydroxysultaine (liquid), and sodium lauroamphoacetate (liquid) were used. Note that the shape of each component is as it is at room temperature (20°C).

[0048] [Table 1]

[0049] Ten g of the obtained test substance was subjected to sonication, and its solubility was confirmed according to the following criteria.

[0050] • Criteria for evaluating solubility Completely dissolves in less than 1 hour: Good Completely dissolves in 1 to 3 hours: Fairly good After 3 hours, some has dissolved, but some remains undissolved: Slightly poor quality. After 3 hours, it has not dissolved at all: defective.

[0051] [Table 2]

[0052] The results are shown in Table 2. As shown in Table 2, when the cannabidiol and nonionic surfactant according to Examples 1 to 5 were included, the solubility was superior to that of Comparative Examples 1 to 8. Furthermore, as shown in Table 2, when the cannabidiol and nonionic surfactant according to Examples 1 to 4 were included, the solubility was even superior to that of Example 5. From these results, it can be concluded that the present invention is extremely effective in improving the solubility of formulations containing cannabidiol.

[0053] [Test 2: Transdermal absorption enhancement effect test] The topical skin preparation of the present invention was prepared according to the composition shown in Table 3. For cannabidiol, we used CBD powder refined from natural sources (CBD content of 98.0% or higher). As nonionic surfactants, PEG-20 glyceryl isostearate (HLB value 13.0, liquid), PEG-60 hydrogenated castor oil (HLB value 14.0, liquid), laureth-9 (HLB value 14.5, liquid), polysorbate 60 (HLB value 14.9, liquid), and PEG-40 stearate (HLB value 17.5, solid) were used. Note that the shape of each component is as it is at room temperature (20°C).

[0054] [Table 3]

[0055] 1. Preparation of buffer A buffer was prepared by mixing polyethylene glycol 400 with PBS to a concentration of 40% (v / v). 2. Cell culture and addition of test substance (1) A human 3D cultured epidermal model ("Labcyte Epi-Model 24" from Japan Tissue Engineering Co., Ltd.) was transferred to a 24-well plate containing assay medium and acclimatized in a 37°C, 5% CO2 incubator for more than 1 hour. (2) After washing the outside of the culture cup twice with 600 μL of PBS, the contents were transferred to an empty 24-well plate. The lid was opened and the plate was placed in a clean bench for 30 minutes to allow the surface of the epidermal tissue to dry. (3) 500 μL of buffer was added to a new 24-well plate. (4) As a sample at hour 0, 200 μL of buffer (permeate) was collected from the 24-well plate before the addition of the test substance. An equal volume of buffer was added to each well. (5) 400 μL of the test substance was added to a human 3D cultured epidermal model ("LabSight Epi-Model 24" from Japan Tissue Engineering Co., Ltd.). The samples were transferred to each well of (4) above and cultured in a 37°C, 5% CO2 incubator. (6) 0.5 hours after the addition of the test substance, 200 μL of the buffer (permeate) on the outside of the culture cup was collected, and an equal volume of buffer was added to the well. Similarly, 200 μL of the buffer (permeate) on the outside of the culture cup was collected at 1 hour, 2 hours, and 3 hours after the addition of the test substance, and an equal volume of buffer was added to the well. (7) Six hours after the addition of the test substance, 200 μL of the buffer (permeate) on the outside of the culture cup was collected. 3. Measurement of cannabidiol concentration (1) The permeates collected in (4), (6), and (7) of 2 above were concentrated and redissolved in acetonitrile, and the concentration of cannabidiol in the permeate was measured by liquid chromatography (HPLC). (2) The amount of cannabidiol that permeated the cells was evaluated from the concentration of cannabidiol in the permeate at each time point. The relative value was calculated with the cannabidiol permeability of Test Example 1 set to 100%.

[0056] The results are shown in Table 4 and Figure 1. From the results in Figure 1, it can be seen that in Test Examples 1 to 4, when cannabidiol and a liquid nonionic surfactant with an HLB value of 13.0 or higher and less than 17.5 were included, the transdermal absorption rate was higher compared to when cannabidiol and a solid nonionic surfactant with an HLB value of 17.5 were included. Therefore, it was found that the transdermal absorption enhancer according to the present invention is excellent in promoting the absorption of cannabidiol into the skin.

[0057] [Table 4]

[0058] As is clear from the above test results, the present invention provides a topical skin preparation in which the permeability of cannabidiol into the skin is enhanced and which has excellent solubility.

[0059] [Manufacturing Examples 1-6] A topical skin preparation, in the form of a lotion, was manufactured according to the composition described in Table 5 below. Specifically, the aqueous phase component and the oil phase component were prepared and emulsified at a predetermined temperature. The topical skin preparation obtained in the manufacturing example below exhibits a high transdermal absorption-promoting effect of cannabidiol and is excellent in cell activation, anti-aging, skin roughness improvement, and whitening effects.

[0060] [Table 5]

[0061] [Manufacturing Examples 7-12] A beauty serum was prepared according to the composition shown in Table 6 below. Specifically, the following beauty serum was obtained by adding the dissolved oil phase while stirring the aqueous phase and stirring until uniform. The topical skin preparation obtained in the following manufacturing example has a high transdermal absorption-promoting effect of cannabidiol and is excellent in cell activation, anti-aging, skin roughness improvement, whitening and cell activation effects.

[0062] [Table 6]

[0063] [Manufacturing Examples 13-18] An emulsion was prepared according to the composition shown in Table 7 below. Specifically, the emulsion was obtained by adding the dissolved oil phase while stirring the aqueous phase and stirring until homogeneous. The topical skin preparation obtained in the following manufacturing example has a high transdermal absorption-promoting effect of cannabidiol and is excellent in cell activation, anti-aging, skin roughness improvement, whitening and cell activation effects.

[0064] [Table 7]

[0065] [Manufacturing Examples 19-24] A cream, which is an oil-in-water emulsion, was prepared according to the composition shown in Table 8 below. Specifically, the following cream was obtained by adding the dissolved oil phase while stirring the aqueous phase and stirring until homogeneous. The topical skin preparation obtained in the following manufacturing example has a high transdermal absorption-promoting effect of cannabidiol and is excellent in cell activation, anti-aging, skin roughness improvement, whitening and cell activation effects.

[0066] [Table 8] [Industrial applicability]

[0067] According to the present invention, it is possible to provide a topical skin preparation that has excellent solubility of cannabidiol and enhanced skin permeability. In particular, by incorporating a nonionic surfactant to improve the solubility of cannabidiol and as a skin absorption enhancer, the solubility and skin permeability of cannabidiol can be enhanced. Furthermore, according to the present invention, in a topical skin preparation selected from lotions, serums, creams, emulsions, all-in-one gels, packs, cleansers, and soaps containing cannabidiol and a nonionic surfactant, by incorporating a nonionic surfactant with an HLB value greater than 9.7 to improve the solubility of cannabidiol and as a skin absorption enhancer, the solubility and skin permeability of cannabidiol can be further enhanced.

Claims

1. A topical skin preparation characterized by containing (a) cannabidiol and (b) a nonionic surfactant, wherein component (b) is at least one selected from fatty acid polyoxyethylene glyceryl, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, and PEG-40 stearate.

2. (b) The topical skin preparation according to claim 1, characterized in that the component is a nonionic surfactant with an HLB value greater than 9.

7.

3. (b) The topical skin preparation according to claim 1 or 2, characterized in that the component is a nonionic surfactant with an HLB value of 13 or higher.

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