Cosmetic composition

Abstract

Provided are: a novel transdermal penetration enhancer for a water-soluble active ingredient; and a cosmetic composition comprising the novel transdermal penetration enhancer. A cosmetic composition containing a polymer having a structure represented by formula (1) and a water-soluble active ingredient, in formula (1), R1, R2, and R3 are each independently a hydrogen atom or a C1-4 alkyl group, A is a C2-4 alkylene group, m and n are each independently 1.0-50, the number average molecular weight of the polymer is 10,000 or less, and the IOB value of the polymer is 0.4-1.8. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to a cosmetic composition. Background Art

[0002] The stratum corneum, which is located on the outermost layer of the skin, has a hydrophobic barrier function, and thus has the property that moisture and water-soluble active ingredients are not easily permeated.

[0003] So far, a large number of percutaneous penetration enhancers for effectively permeating moisture, water-soluble active ingredients, etc. into the skin or cosmetic compositions containing such percutaneous penetration enhancers have been developed.

[0004] For example, Patent Document 1 discloses a topical skin preparation containing an alkylene oxide derivative represented by the following general formula (I), and discloses that the alkylene oxide derivative has a percutaneous absorption promoting effect:

[0005] R 1 O-[(AO) m (EO) n -R 2 (I)

[0006] In addition, Patent Document 2 discloses a cosmetic composition as a cosmetic composition that improves the permeability of an active ingredient into the skin and prolongs the residence time of the active ingredient in the skin, and is a cosmetic composition suitable for topical application, which contains: i) glycerin, ii) a lipid bilayer structuring agent having a glycerol head group, iii) a penetration enhancer, and iv) a skin care active ingredient.

[0007] In addition, Patent Document 3 discloses a skin penetration enhancer for at least one hydroxy acid for the purpose of increasing the skin penetration of a hydroxy acid, which contains (b) at least one basic amino acid, (c) at least one amino acid-based surfactant selected from N-acyl aspartic acid and its derivatives, and (d) water.

[0008] Prior Art Documents

[0009] Patent Documents

[0010] Patent Document 1: Japanese Patent Application Laid-Open No. 2004-083541

[0011] Patent Document 2: Japanese Patent Application Laid-Open No. 2017-500322

[0012] Patent Document 3: Japanese Patent Application Laid-Open No. 2019-116421 Summary of the Invention

[0013] Problems to be Solved by the Invention

[0014] Although the effects of specific components on the penetration into the skin have been studied to a certain extent, there is still room for improvement regarding the penetration of water-soluble active ingredients into the skin.

[0015] The present invention aims to improve the above situation, and its object is to provide a new percutaneous penetration enhancer for water-soluble active ingredients and a cosmetic composition containing the new percutaneous penetration enhancer.

[0016] Means for solving the problem

[0017] The present invention for achieving the above object is as described below.

[0018] <Scheme 1>

[0019] A composition, which is a cosmetic composition containing a polymer having a structure represented by the following formula (1) and a water-soluble active ingredient,

[0020]

[0021] In the above formula (1), R 1 , R 2 and R 3 are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, A is an alkylene group having 2 to 4 carbon atoms, and m and n are each independently 1.0 to 50,

[0022] The number average molecular weight of the above polymer is 10,000 or less, and

[0023] The IOB value of the above polymer is 0.4 to 1.8.

[0024] <Scheme 2>

[0025] The composition according to Scheme 1, in the above formula (1), A is represented by the following formula (2),

[0026]

[0027] In the above formula (2), R 4 is an alkyl group having 1 or 2 carbon atoms.

[0028] <Scheme 3>

[0029] The composition according to Scheme 1 or 2, the above polymer is a random copolymer.

[0030] <Scheme 4>

[0031] The composition according to any one of Schemes 1 to 3, in the above formula (1), m is 2 or more, and at least a part of R 1 is methyl.

[0032] <Scheme 5>

[0033] For the composition according to any one of Schemes 1 to 4, in the above formula (1), R 2 and R 3 At least one of them is methyl.

[0034] <Scheme 6>

[0035] For the composition according to any one of Schemes 1 to 5, the above water-soluble active ingredient comprises an ionic substance or a non-ionic substance with a logP value of less than 2.0.

[0036] <Scheme 7>

[0037] For the composition according to any one of Schemes 1 to 6, the above water-soluble active ingredient comprises at least one selected from alkoxysalicylic acid or its salt, 1-piperidinepropionic acid or its salt, vitamin B group or its derivatives, and amino acid or its derivatives.

[0038] <Scheme 8>

[0039] For the composition according to any one of Schemes 1 to 7, the above polymer is a percutaneous penetration enhancer for the above water-soluble active ingredient.

[0040] <Scheme 9>

[0041] An application is an application of a polymer having a structure represented by the following formula (1) as a percutaneous penetration enhancer for a water-soluble active ingredient,

[0042]

[0043] In the above formula (1), R 1 , R 2 and R 3 Are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, A is an alkylene group having 2 to 4 carbon atoms, and m and n are each independently 1.0 to 50,

[0044] The number average molecular weight of the above polymer is 10,000 or less, and

[0045] The IOB value of the above polymer is 0.4 to 1.8.

[0046] <Scheme 10>

[0047] For the application according to Scheme 9, in the above formula (1), A is represented by the following formula (2),

[0048]

[0049] In the above formula (2), R 4 Is an alkyl group having 1 or 2 carbon atoms.

[0050] <Scheme 11>

[0051] For the application according to Scheme 9 or 10, the above polymer is a random copolymer.

[0052] <Scheme 12>

[0053] For the application according to any one of Schemes 9 to 11, in the above formula (1), m is 2 or more, and at least a part of R 1 is methyl.

[0054] <Scheme 13>

[0055] For the application according to any one of Schemes 9 to 12, in the above formula (1), at least one of R 2 and R 3 is methyl.

[0056] <Scheme 14>

[0057] For the application according to any one of Schemes 9 to 13, the above water-soluble active ingredient contains an ionic substance or a non-ionic substance with a logP value less than 2.0.

[0058] <Scheme 15>

[0059] For the application according to any one of Schemes 9 to 14, the above water-soluble active ingredient contains at least one selected from alkoxysalicylic acid or its salt, 1-piperidinepropionic acid or its salt, vitamin B group or its derivatives, and amino acid or its derivatives.

[0060] Effects of the Invention

[0061] According to the present invention, a new percutaneous penetration enhancer for a water-soluble active ingredient and a cosmetic composition containing the new percutaneous penetration enhancer can be provided. Description of the Drawings

[0062] Figure 1 It is a graph showing the results of the cumulative permeation amount of the water-soluble active ingredient in Example 1, Example 2, and Comparative Example 1.

[0063] Figure 2 It is a graph showing the results of the cumulative permeation amount of the water-soluble active ingredient in Example 3 and Comparative Example 2.

[0064] Figure 3 It is a graph showing the results of the cumulative permeation amount of the water-soluble active ingredient in Example 4, Example 5, and Comparative Example 3.

[0065] Figure 4A graph showing the results of the cumulative permeation amounts of D-glutamic acid contained in the water-soluble active ingredients of Example 6, Example 7, and Comparative Example 4.

[0066] Figure 5 A graph showing the results of the cumulative permeation amounts of DL-alanine contained in the water-soluble active ingredients of Example 6, Example 7, and Comparative Example 4.

[0067] Figure 6 A graph showing the results of the cumulative permeation amounts of DL-methionine contained in the water-soluble active ingredients of Example 6, Example 7, and Comparative Example 4. Detailed Description of the Invention

[0068] Hereinafter, embodiments of the present invention will be described in detail. It should be noted that the present invention is not limited to the following embodiments, and various modifications can be made within the scope of the intention of the invention.

[0069] "Cosmetic Composition"

[0070] The cosmetic composition of the present invention (hereinafter, also simply referred to as "the composition of the present invention") is the following composition,

[0071] which is a cosmetic composition containing a polymer having the structure represented by the following formula (1) (hereinafter, also simply referred to as "the polymer of the present invention") and a water-soluble active ingredient.

[0072]

[0073] In formula (1), R 1 , R 2 and R 3 are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, A is an alkylene group having 2 to 4 carbon atoms, and m and n are each independently 1.0 to 50.

[0074] The number average molecular weight of the polymer is 10,000 or less, and

[0075] the IOB value of the polymer is 0.4 to 1.8.

[0076] "The Polymer of the Present Invention"

[0077] The composition of the present invention contains the polymer of the present invention described below. The polymer of the present invention has the effect of enhancing the permeability of the water-soluble active ingredient into the skin. Therefore, the polymer of the present invention can also be said to be a percutaneous penetration enhancer for the water-soluble active ingredient. In other words, the polymer of the present invention can be used as a percutaneous penetration enhancer for the water-soluble active ingredient contained in the composition of the present invention.

[0078] Although not limited by theory, it is speculated that the above characteristics of the polymer of the present invention are derived from the unique structure shown in Formula (1), the number-average molecular weight within a specific range (10,000 or less), and the IOB (Inorganic Organic Balance) value within a specific range (0.4 to 1.8).

[0079] Furthermore, through in-depth research by the inventors of the present invention, it has been found that the polymer of the present invention can interact with the intercellular lipids of the stratum corneum. It is speculated that although the intercellular lipids of the stratum corneum usually hinder the penetration of substances such as water-soluble active ingredients into the skin, if the intercellular lipids interact with the polymer of the present invention, they will temporarily become unstable. At this moment, water-soluble active ingredients and the like can more easily penetrate into the skin, that is, the permeability of water-soluble active ingredients is increased.

[0080] It should be noted that in the present invention, "transdermal penetration promotion" means rapid penetration into the skin. Therefore, when using the "transdermal penetration enhancer" of the present invention, the water-soluble active ingredient can penetrate more rapidly compared to the case where it is not used.

[0081] The polymer of the present invention has the structure shown in the following Formula (1):

[0082]

[0083] In Formula (1), R 1 , R 2 and R 3 are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. It should be noted that in the present invention, examples of the alkyl group having 1 to 4 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, and tert-butyl. In addition, as long as the effects of the present invention are not impaired, these alkyl groups may further have substituents. The substituents are not particularly limited, and examples include halogenated groups.

[0084] According to an embodiment of the present invention, in Formula (1), R 1 , R 2 and R 3 can each independently be a hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, or tert-butyl.

[0085] According to an embodiment of the present invention, in Formula (1), R 1 is preferably a hydrogen atom, methyl, or ethyl. In addition, when m is 2 or more, that is, when there are multiple R 1 , each R 1 can be the same or different. In particular, it is preferred that at least a part of R 1 is methyl. When R1 When at least a part of it is methyl, for example, it is preferable from the viewpoint of improving the usability of the composition of the present invention.

[0086] According to one embodiment of the present invention, in formula (1), R 1 may also be in a state where a hydrogen atom and an alkyl group having 1 to 4 carbon atoms coexist. That is, R 1 may have a part as a hydrogen atom and another part as an alkyl group having 1 to 4 carbon atoms. Preferably, a part of R 1 is a hydrogen atom and another part is a methyl group.

[0087] According to one embodiment of the present invention, in formula (1), R 2 is preferably a hydrogen atom, a methyl group or an ethyl group, and particularly more preferably a methyl group.

[0088] According to one embodiment of the present invention, in formula (1), R 2 may also be in a state where a hydrogen atom and an alkyl group having 1 to 4 carbon atoms coexist. That is, R 2 may have a part as a hydrogen atom and another part as an alkyl group having 1 to 4 carbon atoms. Preferably, a part of R 2 is a hydrogen atom and another part is a methyl group.

[0089] According to one embodiment of the present invention, in formula (1), R 3 is preferably a hydrogen atom, a methyl group or an ethyl group, and particularly more preferably a methyl group.

[0090] According to one embodiment of the present invention, in formula (1), preferably at least one of R 2 and R 3 is a methyl group.

[0091] In formula (1), A is an alkylene group having 2 to 4 carbon atoms. More specifically, A may be, for example, ethylene, propylene, butylene, isobutylene, etc., but is not limited to these. In particular, A is preferably represented by the following formula (2):

[0092]

[0093] In formula (2), R 4 is an alkyl group having 1 or 2 carbon atoms. More specifically, R 4 may be a methyl group or an ethyl group.

[0094] In formula (1), m and n represent the average addition molar numbers of the respective structural units. m and n are each independently from 1.0 to 50, more specifically, they can be 1.0 or more, 1.5 or more, 2.0 or more, 3.0 or more, 4.0 or more, 5.0 or more, 6.0 or more, 7.0 or more, 8.0 or more, 9.0 or more, or 10 or more. Additionally, they can be 50 or less, 45 or less, 40 or less, 35 or less, 34 or less, 32 or less, 30 or less, 28 or less, 26 or less, 25 or less, 24 or less, 22 or less, 20 or less, 18 or less, 16 or less, 15 or less, 14 or less, 12 or less, 10 or less, or 5.0 or less.

[0095] Furthermore, in formula (1), m is preferably 1.0 or more and 14 or less, more preferably 2.0 or more and 5.0 or less. Additionally, in formula (1), n is preferably 2.0 or more and 34 or less, more preferably 6.0 or more and 12 or less.

[0096] According to an embodiment of the present invention, in formula (1), m + n can be 4.0 or more, 4.5 or more, 5.0 or more, 6.0 or more, 7.0 or more, 8.0 or more, 9.0 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more. Additionally, it can be 50 or less, 45 or less, 40 or less, 35 or less, 30 or less, 25 or less, 20 or less, 15 or less, or 12 or less.

[0097] According to an embodiment of the present invention, in formula (1), m:n can be from 1:10 to 10:1.

[0098] The number-average molecular weight of the polymer of the present invention is 10,000 or less. More specifically, the number-average molecular weight of the polymer of the present invention can be, for example, 10,000 or less, 5,000 or less, 3,500 or less, 3,200 or less, 3,000 or less, 2,800 or less, 2,500 or less, 2,200 or less, 2,000 or less, 1,800 or less, 1,500 or less, 1,400 or less, 1,300 or less, 1,200 or less, 1,100 or less, 1,000 or less, 900 or less, 800 or less, 700 or less, or 600 or less. Additionally, it can be 130 or more, 150 or more, 200 or more, 250 or more, 300 or more, 350 or more, 400 or more, 450 or more, 500 or more, 550 or more, 600 or more, 650 or more, 700 or more, 750 or more, 800 or more, 850 or more, 900 or more, 950 or more, or 1,000 or more. Furthermore, the number-average molecular weight of the polymer of the present invention is preferably 300 or more and 3,500 or less, more preferably 500 or more and 1,200 or less.

[0099] The IOB value of the polymer of the present invention is 0.4 to 1.8. More specifically, the IOB value of the polymer of the present invention can be, for example, 0.4 or more, 0.5 or more, 0.6 or more, 0.7 or more, 0.8 or more, 0.9 or more, or 1.0 or more, and can also be 1.8 or less, 1.6 or less, 1.4 or less, or 1.2 or less. In addition, the IOB value of the polymer of the present invention is preferably 0.7 or more and 1.2 or less.

[0100] Here, the IOB value is an abbreviation of Inorganic / Organic Balance, and is a value representing the ratio of the inorganic value to the organic value, and is an index representing the degree of polarity of an organic compound. Specifically, the IOB value is expressed as IOB value = inorganic value / organic value. Regarding each of the "inorganic value" and "organic value", for example, the "inorganic value" and "organic value" corresponding to various atoms or functional groups are set in such a way that the "organic value" is 20 for one carbon atom in the molecule and the "inorganic value" is 100 for one hydroxyl group. By accumulating the "inorganic value" and "organic value" of all atoms and functional groups in the organic compound, the IOB value of the organic compound can be calculated (see, for example, Yoshio Koda, "Organic Concept Map - Basics and Applications -", p. 11-17, Sankyo Publishing, published in 1984). It should be noted that regarding the method for determining the IOB value, reference can be made to the method described in the examples.

[0101] The polymer of the present invention can be a block copolymer or a random copolymer, but a random copolymer is preferred.

[0102] The method for producing the polymer of the present invention is not particularly limited. For example, it is preferable to carry out polyaddition of epoxides corresponding to each structural unit. In addition, the polyaddition can be block polymerization or random polymerization, but random polymerization is preferred.

[0103] In addition, the method for producing the polymer of the present invention can further include: further reacting a haloalkane with the polymer obtained by the above polyaddition. Through the reaction with the haloalkane, the hydroxyl groups in the molecule of the resulting polymer are blocked by alkyl groups, and as a result, the overall hydrophobicity of the polymer can be adjusted as desired. In the present invention, in the molecule of the polymer, the blocking rate of the hydroxyl groups by alkyl groups can be, for example, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, or 55% or more, and can also be 60% or less, 59% or less, 58% or less, 57% or less, 56% or less, or 55% or less. It should be noted that the blocking rate of the hydroxyl groups by alkyl groups can be determined by the method described in the examples.

[0104] One of the characteristics of the polymer of the present invention is that it has both high water solubility and high fat solubility.

[0105] The solubility of the polymer of the present invention in water can be, for example, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, 45% by mass or more, or 50% by mass or more.

[0106] In addition, as an index of the fat solubility of the polymer of the present invention, the solubility in olive oil can be used, for example. The solubility of the polymer of the present invention in olive oil can be, for example, 0.01% by mass or more, 0.05% by mass or more, 0.10% by mass or more, 0.50% by mass or more, or 1.00% by mass or more. It should be noted that the upper limit of the solubility of the polymer of the present invention in olive oil is not particularly limited and can be, for example, 10% by mass or less.

[0107] In the composition of the present invention, the content of the polymer of the present invention is not particularly limited. For example, it can be 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1.0% by mass or more, 2.0% by mass or more, 3.0% by mass or more, 4.0% by mass or more, or 5.0% by mass or more. In addition, it can be 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 8.0% by mass or less, 5.0% by mass or less, 3.0% by mass or less, or 1.0% by mass or less.

[0108] In addition, when the polymer of the present invention is used as a transdermal penetration enhancer for water-soluble active ingredients, it can be, for example, 1.0 part by mass or more, 5.0 parts by mass or more, preferably 10 parts by mass or more, 50 parts by mass or more, 100 parts by mass or more, 130 parts by mass or more, 150 parts by mass or more, 200 parts by mass or more, 250 parts by mass or more, 300 parts by mass or more, 350 parts by mass or more, 400 parts by mass or more, 450 parts by mass or more, or 500 parts by mass or more, based on a total of 100 parts by mass of the water-soluble active ingredients. In addition, it can be 10,000 parts by mass or less, 5,000 parts by mass or less, or 3,000 parts by mass or less, and preferably 1,000 parts by mass or less.

[0109] 〈Water-soluble active ingredient〉

[0110] The composition of the present invention contains a water-soluble active ingredient. In the present invention, the so-called "water-soluble active ingredient" refers to an ingredient that is water-soluble and exerts its function by penetrating into the skin. Here, the function of the water-soluble active ingredient is not particularly limited, and refers to the ability to bring certain effects, particularly beneficial effects (such as moisturizing effect, firming effect, whitening effect, anti-wrinkle effect or anti-spot effect, etc.) to the skin.

[0111] In the present invention, the water-soluble active ingredient is not particularly limited, and may include, for example, ionic substances or non-ionic substances with a logP value of less than 2.0.

[0112] It should be noted that here, the "ionic substance" includes salts of metal ions that are completely ionized in water (such as potassium 4-methoxysalicylate), etc. In addition, "metal ions" include alkali metal ions and alkaline earth metal ions. More specifically, they include, for example, sodium ions, potassium ions or calcium ions, etc., but are not limited to these.

[0113] In addition, the so-called "logP value" represents the ratio of the equilibrium concentrations of a substance dissolved in the two phases of octanol and water, and is an index indicating the hydrophilic-lipophilic balance of the component (non-ionic substance). In particular, it is known that when the logP value is around 2.0, the skin permeability of the component (non-ionic substance) is extremely high, and when the logP value is less than this, the skin permeability of the component (non-ionic substance) becomes smaller (for example, "Non-formulation Parameters That Affect Penetrant-Skin-Vehicle Interactions and Percutaneous Absorption", by JE Grice et al., "Percutaneous Penetration Enhancers Drug Penetration Into / Through the Skinpp" (2017), PP. 45-75). Therefore, in the present invention, the lgoP value of the non-ionic substance as a water-soluble active ingredient can be less than 2.0, 1.9 or less, 1.8 or less, 1.7 or less, 1.6 or less, 1.5 or less, 1.4 or less, 1.3 or less, 1.2 or less, 1.1 or less, 1.0 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, 0.1 or less, 0.0 or less, -0.1 or less, -0.2 or less, -0.3 or less, -0.4 or less, -0.5 or less, -0.6 or less, -0.7 or less, -0.8 or less, -0.9 or less, -1.0 or less, -1.1 or less, -1.2 or less, -1.3 or less, -1.4 or less, -1.5 or less, -1.6 or less, -1.7 or less, -1.8 or less, -1.9 or less, or -2.0 or less. In addition, the lower limit value of the logP value is not particularly limited, and can be, for example, -8.0 or more, -7.0 or more, -5.0 or more, or -3.0 or more.

[0114] It should be noted that regarding the logP value, for example, the logP values of a large number of compounds are published in databases that can be obtained from Daylight Chemical Information Systems, Inc. (Daylight CIS) or PubChem (National Center for Biotechnology Information), etc., and can be referred to. In addition, in the case where there is no measured logP value, it can be calculated using a program such as "CLOGP" (Daylight CIS).

[0115] In the present invention, specific examples of the ionic substances used as water-soluble active ingredients are shown below, but are not limited thereto. That is, as the ionic substances, for example, salts of alkoxysalicylic acid, particularly metal ion salts of alkoxysalicylic acid (e.g., potassium 4-methoxysalicylate, etc.), thrombin acid salts, L-ascorbate, magnesium ascorbyl phosphate, dipotassium glycyrrhizinate, and ionic vitamins B such as vitamin B1 and vitamin B12, etc. can be cited.

[0116] In the present invention, specific examples of the non-ionic substances with a logP value of less than 2.0 used as water-soluble active ingredients are shown below, but are not limited thereto. That is, as the non-ionic substances with a logP value of less than 2.0, for example, it can include at least one selected from alkoxysalicylic acid with a logP value of less than 2.0, vitamin B group with a logP value of less than 2.0 or its derivatives, thrombin acid (logP value: -2.0), L-ascorbic acid (logP value: -1.6), arbutin (logP value: -0.7), L-ascorbic acid glucoside (logP value: -3.1), glycylglycine (logP value: -2.3), 1-(2-hydroxyethyl)-2-imidazolidinone (logP value: -1.4), adenosine (logP value: -1.1), DIPY (dimethylpyrazolyl dimethylpyrimidine hydrochloride; logP value: 0.8), taurine (logP value: 1.4), betaine (logP value: 0.1), pyridoxine (logP value: -0.8), sodium pyrrolidonecarboxylate (logP value: -0.8), 1PP (1-piperidinepropionic acid; logP value: -1.5), vitamin C (logP value: -2.2), vitamin C glucoside (logP value: -3.1), ethyl vitamin C (logP value: -1.5), glycerol (logP value: -1.8), 1,3-butanediol (logP value: -0.4), dipropylene glycol (logP value: -0.5), trehalose (logP value: -1.7), xylitol (logP value: -2.5), sodium lactate (logP value: -0.7), urea (logP value: -2.1) and other humectants, hyaluronic acid (logP value: -7.4), and amino acids (logP value: -1.0 to -4.0) such as glutamic acid (logP value: -3.7), alanine (logP value: -3.0), methionine (logP value: -1.9) and their derivatives (including optical isomers).

[0117] Among the above, in the present invention, the water-soluble active ingredient preferably contains at least one selected from alkoxysalicylic acid or its salt, 1-piperidinepropionic acid or its salt, vitamin B group or its derivatives, and amino acid or its derivatives.

[0118] (alkoxysalicylic acid or its salt)

[0119] The alkoxysalicylic acid that can be used in the present invention is a substance in which any one of the hydrogen atoms at the 3-position, 4-position or 5-position of salicylic acid is replaced by an alkoxy group. The alkoxy group as a substituent is preferably any one of methoxy, ethoxy, propoxy, isopropoxy, butoxy, and isobutoxy, and more preferably methoxy or ethoxy.

[0120] If specific compounds of alkoxysalicylic acid are exemplified, 3-methoxysalicylic acid (logP value: 1.9) etc. can be cited.

[0121] The salt (ionic substance) of alkoxysalicylic acid is not particularly limited. For example, in addition to alkali metal salts or alkaline earth metal salts such as sodium salt, potassium salt, and calcium salt, salts such as ammonium salt and amino acid salt can also be cited.

[0122] (1-Piperidinepropionic acid and its salts)

[0123] 1-Piperidinepropionic acid is a compound represented by the following chemical formula:

[0124]

[0125] The salt (ionic substance) of 1-piperidinepropionic acid is not particularly limited. For example, in addition to alkali metal salts or alkaline earth metal salts such as sodium salt, potassium salt, and calcium salt, salts such as ammonium salt and amino acid salt can also be cited.

[0126] (Vitamin B group and its derivatives)

[0127] In the present invention, the vitamin B group or its derivatives include, for example, one or more compounds selected from vitamin B1 (ionic substance), vitamin B2 (logP value: -1.5), vitamin B3 (also called "nicotinic acid"), vitamin B5 (logP value: -1.1), vitamin B6 (logP value: -0.8), and vitamin B12 (ionic substance), and their derivatives. Particularly preferably, it includes vitamin B3 also called "nicotinic acid" or its derivatives. It should be noted that "nicotinic acid" includes nicotinic acid and nicotinamide (also called "niacinamide"). Here, from the viewpoint that nicotinamide has both whitening effect and anti-wrinkle effect, in the present invention, the vitamin B group or its derivatives are preferably nicotinamide (logP value: -0.4).

[0128] (Amino acids and their derivatives (including optical isomers))

[0129] In the present invention, the amino acid or its derivatives (including optical isomers) are not particularly limited. More specifically, the amino acid can include, for example, at least one selected from glutamic acid (logP value: -3.7), alanine (logP value: -3.0), and methionine (logP value: -1.9).

[0130] Here, the so-called derivative of an amino acid refers to a substance that, although somewhat different in structure, has the same or similar characteristics as the amino acid. For example, it can be an optical isomer (D-form, L-form, or DL-form) of an amino acid, or an amino acid in which an amino group or a carboxyl group is modified with a protecting group or the like. However, ionic substances among the derivatives of amino acids can be classified as the above-mentioned "ionic substances".

[0131] In the composition of the present invention, the content of the water-soluble active ingredient is not particularly limited. For example, it can be 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1.0% by mass or more, 1.5% by mass or more, 2.0% by mass or more, 3.0% by mass or more, 4.0% by mass or more, or 5.0% by mass or more. In addition, it can be 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 8.0% by mass or less, 5.0% by mass or less, 3.0% by mass or less, 2.0% by mass or less, or 1.0% by mass or less.

[0132] (Other components)

[0133] In addition to the above-mentioned polymer and water-soluble active ingredient of the present invention, the composition of the present invention may further contain one or more components that are commonly used in skin external preparations such as cosmetics and pharmaceuticals as other components.

[0134] Specific examples of other components include, for example, powder components, liquid oils and fats, solid oils and fats, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicones, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, water-soluble polymers, thickeners, film-forming agents, ultraviolet absorbers, sequestering agents, lower alcohols, polyhydric alcohols, sugars, amino acids, organic amines, polymer emulsions, pH adjusters, skin nutrients, vitamins, antioxidants, antioxidant aids, fragrances, water, etc., but are not limited to these.

[0135] (Dosage form and product form of the composition)

[0136] The dosage form of the composition of the present invention is not particularly limited and can be, for example, a solution system, solubilization system, emulsion system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, gel, mist, spray, mousse, roll-on, stick, etc., or can be a preparation such as a sheet impregnated or coated with a non-woven fabric or the like.

[0137] In addition, the form of the product of the composition of the present invention is not particularly limited and may be, for example, facial cosmetics such as lotions, milks, creams, and masks; color cosmetics such as foundations, lipsticks, and eyeshadows; sunscreen cosmetics (sunscreen agents); body cosmetics; fragrance cosmetics; skin cleaning agents such as makeup removers and body shampoos; hair cosmetics such as hair liquids, hair tonics, hair conditioners, shampoos, rinses, and hair growth agents; or ointments, etc.

[0138] <Use of the Polymer of the Present Invention>

[0139] The present invention also provides the use of the polymer of the present invention as a percutaneous penetration enhancer for water-soluble active ingredients.

[0140] Here, for the details of the water-soluble active ingredients and the mixing amount thereof when using the polymer of the present invention as a percutaneous penetration enhancer for water-soluble active ingredients, reference may be appropriately made to the item of "the composition of the present invention" above.

[0141] Examples

[0142] Examples are given below to further illustrate the present invention in detail, but the present invention is not limited to these.

[0143] <Synthesis Examples 1 and 2>

[0144] In the following, Synthesis Examples 1 and 2 respectively synthesized polymers having the structure shown in the following formula (3):

[0145]

[0146] It should be noted that in formula (3), the content within [] is a random copolymer.

[0147] <Synthesis Example 1>

[0148] Synthesis Example 1: R 1 = H, R 2 = H, R 3 = CH3, R 4 = CH3, m = 2.0 and n = 6.0 of Polymer 1

[0149] It was synthesized by the following method to obtain Polymer 1.

[0150] 128 g of methanol and 6.4 g of potassium hydroxide as a catalyst were added to an autoclave. After replacing the air in the autoclave with dry nitrogen, the catalyst was completely dissolved at 80 °C with stirring. Next, a mixture of 592 g of glycidol and 1392 g of propylene oxide was added dropwise at 95 °C over 20 hours through a dropping device, and then stirred for 5 hours. The reaction composition was taken out from the autoclave, neutralized with hydrochloric acid to a pH of 6 - 7, and treated at -0.095 MPa (50 mmHg) and 100 °C for 1 hour to remove the contained water. Further, filtration was carried out to remove the salt formed after the treatment, and 2000 g of the polymer 1 of Synthesis Example 1 was obtained.

[0151] Hereinafter, various physical property values were determined for the obtained polymer 1.

[0152] (Number average molecular weight)

[0153] The number average molecular weight of the obtained polymer 1 was calculated by measurement with gel permeation chromatography (GPC). The system was a SHODEX (registered trademark) GPC101 GPC dedicated system, the differential refractive index meter was a SHODEX RI-71s, the guard column was a SHODEX KF-G, the columns were three HODEX KF804L columns installed continuously, the column temperature was 40 °C, tetrahydrofuran as an eluent was flowed at a flow rate of 1 ml / minute, 0.1 ml of a 0.1 wt% tetrahydrofuran solution of the obtained reaction product was injected, and a chromatogram represented by refractive index intensity and elution time was obtained using a BORWIN GPC calculation program. The number average molecular weight was determined with polyethylene glycol as a standard from this chromatogram, and the result was approximately 530.

[0154] (Weight average molecular weight)

[0155] The weight average molecular weight of the obtained polymer 1 was determined by GPC calculation in the same manner as above, and was approximately 859.

[0156] (Polydispersity)

[0157] Based on the results of the number average molecular weight and weight average molecular weight determined above, the polydispersity Mw / Mn of polymer 1 was 1.62.

[0158] (IOB value)

[0159] The IOB value of the obtained polymer 1 was determined as follows, and the result was 1.1.

[0160] More specifically, in polymer 1, as the organic value, carbon was set to 20 and iso-branches were set to -10 for calculation. In addition, regarding the inorganic value, hydroxyl groups were set to 100 and ether bonds were set to 20 for calculation.

[0161] · Methanol moiety: (number of carbon atoms 1, number of hydroxyl groups 1) × 1

[0162] Organic value: 20

[0163] Inorganic value: 100

[0164] · Glycidol moiety: (number of carbon atoms 3, number of iso - branched chains 1, number of hydroxyl groups 1, number of ether bonds 1) × 2

[0165] Organic value: (60 - 10) × 2 = 100

[0166] Inorganic value: (100 + 20) × 2 = 240

[0167] · Propylene oxide moiety: (number of carbon atoms 3, number of iso - branched chains 1, number of ether bonds 1) × 6

[0168] Organic value: (60 - 10) × 6 = 300

[0169] Inorganic value: 20 × 6 = 120

[0170] Above, since the total organic value is 420 and the total inorganic value is 460, the IOB value is 1.09.

[0171] (Cloud point)

[0172] For the obtained Polymer 1, a 5 wt% aqueous solution was prepared, heated to 85 °C, and then cooled. The temperature at which it became a transparent solution was 74 °C. Therefore, it can be known that the cloud point of Polymer 1 is 74 °C.

[0173] (Hydroxyl value)

[0174] The hydroxyl value of the obtained Polymer 1 was measured according to the measurement method of JIS K - 1557 - 1, and the result was 294.

[0175] (Solubility in water)

[0176] The solubility of the obtained Polymer 1 in water was determined in the same manner as the method of "compatibility evaluation" described later, and the result was 50 mass% or more.

[0177] (Solubility in olive oil)

[0178] The solubility of the obtained Polymer 1 in olive oil was determined as follows. That is, Polymer 1 was mixed with olive oil so that the concentration became 1.0 wt%, and the appearance was confirmed. If it was uniform, it was set as "〇". In this case, the solubility of Polymer 1 in olive oil was 1.0 mass%.

[0179] The various physical property values of Polymer 1 measured above are shown in Table 1 below.

[0180] 〈Synthesis Example 2〉

[0181] Synthesis Example 2: R 1 = H and CH3, R 2 = H and CH3, R 3 = CH3, R 4 = CH3, m = 2.0 and n = 6.0 of Polymer 2

[0182] Polymer 2 was synthesized by the following method.

[0183] 128 g of methanol and 6.4 g of potassium hydroxide as a catalyst were added to an autoclave. After displacing the air in the autoclave with dry nitrogen, the catalyst was completely dissolved at 80 °C with stirring. Next, a mixture of 592 g of glycidol and 1392 g of propylene oxide was added dropwise through a dropping device at 95 °C over 20 hours, and then stirred for 2 hours. Next, 244 g of potassium hydroxide was added, and the system was displaced with dry nitrogen. After displacing the system with dry nitrogen, 200 g of chloromethane was pressed in at a temperature of 80 - 130 °C and reacted for 5 hours. Then, the reaction composition was taken out from the autoclave, neutralized with hydrochloric acid to a pH of 6 - 7, and treated at -0.095 MPa (50 mmHg) and 100 °C for 1 hour to remove the contained moisture. Further, filtration was carried out to remove the salt generated after the treatment, and 1820 g of Polymer 2 was obtained. Sampling was carried out before the reaction of chloromethane, and the hydroxyl value after purification was 125. Therefore, it was known that the ratio of methyl to hydrogen atom (CH3 / H) in R 2 and R 3 was 0.57. That is, the hydroxyl group blocking rate of Polymer 2 was 57%.

[0184] Similar to the case of the above Polymer 1, various physical property values of the obtained Polymer 2 were determined, and the respective results are shown in Table 1 below.

[0185] [Table 1]

[0186] (Table 1 Synthesis Example 1 and Synthesis Example 2)

[0187]

[0188] ※1 Regarding the synthesized compound, it was mixed with olive oil so that the concentration became 1.0 mass%, and the appearance was confirmed. If it was uniform, it was designated as "○".

[0189] 〈Compatibility Evaluation〉

[0190] The synthesized polymers 1 and 2 were mixed with water and various oils at a certain concentration, stirred, and then left standing for 1 day. After that, their respective compatibilities were investigated by visual observation. The results are shown in Table 1-2 below. It should be noted that in Table 1-2, "〇" indicates "compatible" and "×" indicates "insoluble".

[0191] [Table 1-2]

[0192] (Table 1-2)

[0193]

[0194] 《Examples 1 and 2, and Comparative Example 1》

[0195] Based on the formulations in Table 2, the respective cosmetic compositions of the examples and comparative examples were prepared. The "cumulative permeation test" of each water-soluble active ingredient into the skin was conducted on the prepared compositions. It should be noted that the values in Table 2, Table 3, and Table 4 described later, and the values in Table 5 other than the pH value refer to the blending amounts of the respective components, with the unit of mass%.

[0196] [Table 2]

[0197] (Table 2)

[0198]

[0199] 〈Cumulative Permeation Test〉

[0200] Regarding the permeability of the prepared compositions, sampling over time was possible. Using a vertical Franz diffusion cell (hereinafter referred to as "Franz cell") also described in the Japanese Pharmacopoeia, the evaluation of the permeation through a simulated skin membrane of various water-soluble pharmaceutical compositions was carried out.

[0201] More specifically, as the Franz cell, one with 1.77 cm was used 2Franz cell with an effective permeation area. As the simulated skin membrane serving as the permeation membrane disposed in the Franz cell, a Strat-M (trademark) film (manufactured by Merck Millipore) cut out with a punching device according to the outer diameter of the supply cell constituting the Franz cell was used. The simulated skin membrane was immersed in physiological phosphate buffer (PBS) before being placed in the Franz cell to be fully hydrated. The water bath and the receiving cell jacket were connected to the Franz cell with a hose. After assembling a series of constant temperature device systems, PBS was filled in the receiving cell. Using the cell clamp, the simulated skin membrane was firmly fixed between the receiving cell and the supply cell in a way that no air entered. The surface temperature of the simulated skin membrane was maintained at about 32 °C equivalent to the surface temperature of the skin using a temperature regulator, and while stirring the PBS in the receiving cell with a stir bar, it was balanced for more than 1 hour. The application of each composition to the simulated skin membrane was carried out by assuming the limited open application in actual use. Each composition was evenly applied to the simulated skin membrane for 30 seconds. After a specified time had passed after application (0, 1, 2, 4, 8, and 24 hours after application), the extract was collected from the receiving cell. Using an HPLC system equipped with an LC-MS detector, the dosage of the drug in the collected extract was quantified to calculate the cumulative permeation amount.

[0202] Figure 1 Results showing the cumulative permeation amounts of the water-soluble active ingredient (niacinamide) in Example 1, Example 2, and Comparative Example 1 are presented.

[0203] From Figure 1 the results, it is clearly known that in both Example 1 containing Polymer 1 and Example 2 containing Polymer 2, compared with the case of Comparative Example 1 that does not contain Polymer 1 and Polymer 2, niacinamide was permeated more rapidly, and its cumulative permeation amount increased significantly.

[0204] 《Example 3 and Comparative Example 2》

[0205] Based on the formulations in Table 3, the cosmetic compositions of Example 3 and Comparative Example 2 were each prepared. The "cumulative permeation test" of each water-soluble active ingredient into the skin was carried out on the prepared compositions.

[0206] [Table 3]

[0207] (Table 3)

[0208]

[0209] Figure 2 Results showing the cumulative permeation amounts of the water-soluble active ingredient (potassium 4-methoxysalicylate) in Example 3 and Comparative Example 2 are presented.

[0210] From Figure 2The results clearly show that in Example 3 containing Polymer 2, potassium 4-methoxysalicylate was permeated more rapidly and its cumulative permeation amount increased significantly compared with that in Comparative Example 2 without Polymer 2.

[0211] 《Examples 4 and 5, and Comparative Example 3》

[0212] Based on the formulations in Table 4, the cosmetic compositions of Examples 4 and 5 and Comparative Example 3 were each prepared. The "cumulative permeation test" of each water-soluble active ingredient into the skin was carried out on the prepared compositions.

[0213] [Table 4]

[0214] (Table 4)

[0215]

[0216] Figure 3 The results showing the cumulative permeation amounts of the water-soluble active ingredient (1-piperidinepropionic acid) in Examples 4 and 5 and Comparative Example 3 are presented.

[0217] It is clearly understood from Figure 3 the results that in both Example 4 containing Polymer 1 and Example 5 containing Polymer 2, 1-piperidinepropionic acid was permeated more rapidly and its cumulative permeation amount increased significantly compared with that in Comparative Example 3 without Polymer 1 and Polymer 2.

[0218] 《Examples 6 to 7 and Comparative Example 4》

[0219] Based on the formulations in Table 5, the cosmetic compositions of Examples 6 to 7 and Comparative Example 4 were each prepared. The "cumulative permeation test" of each water-soluble active ingredient (amino acid or its derivative) into the skin was carried out on the prepared compositions.

[0220] [Table 5]

[0221] (Table 5)

[0222]

[0223] *1: The molecular formula of "D-glutamic acid" is C5H9NO4 and its molecular weight is 147.13.

[0224] *2: The molecular formula of "DL-alanine" is C3H7NO2 and its molecular weight is 89.09.

[0225] *3: The molecular formula of "DL-methionine" is C5H 11 NO2S and its molecular weight is 149.21.

[0226] Figure 4A graph showing the results of the cumulative permeation amounts of D-glutamic acid contained in the water-soluble active ingredients of Example 6, Example 7, and Comparative Example 4.

[0227] From Figure 4 the results, it is clearly understood that in both Example 6 containing Polymer 1 and Example 7 containing Polymer 2, compared with the case of Comparative Example 4 not containing Polymer 1 and Polymer 2, D-glutamic acid was permeated more rapidly, and its cumulative permeation amount increased significantly. In particular, it is understood that in the case of Example 6, the permeation promoting effect of D-glutamic acid was significant.

[0228] Figure 5 A graph showing the results of the cumulative permeation amounts of DL-alanine contained in the water-soluble active ingredients of Example 6, Example 7, and Comparative Example 4.

[0229] From Figure 5 the results, it is clearly understood that in both Example 6 containing Polymer 1 and Example 7 containing Polymer 2, compared with the case of Comparative Example 4 not containing Polymer 1 and Polymer 2, DL-alanine was permeated more rapidly, and its cumulative permeation amount increased significantly. In particular, it is understood that in the case of Example 6, the permeation promoting effect of DL-alanine was significant.

[0230] Figure 6 A graph showing the results of the cumulative permeation amounts of DL-methionine contained in the water-soluble active ingredients of Example 6, Example 7, and Comparative Example 4.

[0231] From Figure 6 the results, it is clearly understood that in both Example 6 containing Polymer 1 and Example 7 containing Polymer 2, compared with the case of Comparative Example 4 not containing Polymer 1 and Polymer 2, DL-methionine was permeated more rapidly, and its cumulative permeation amount increased significantly. In particular, it is understood that in the case of Example 6, the permeation promoting effect of DL-methionine was significant.

[0232] It should be noted that glutamic acid, alanine, and methionine that can be used as water-soluble active ingredients all have the property of having a low logP value and being generally difficult to permeate through the skin (for example, refer to Figures 4 to 6 the results of Comparative Example 4). Therefore, it is clarified that although the permeation promoting effect of these water-soluble active ingredients in Example 7 is slightly worse than that in the case of Example 6, it shows a favorable effect compared with the case of Comparative Example 4.

Claims

1. A cosmetic composition, which is a cosmetic composition comprising a polymer having a structure represented by the following formula (1) and a water-soluble active ingredient, In the formula (1), R 1 , R 2 and R 3 are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, A is an alkylene group having 2 to 4 carbon atoms, and m and n are each independently 1.0 to 50, The number average molecular weight of the polymer is 10,000 or less, and The IOB value of the polymer is 0.4 to 1.

8.

2. The composition according to claim 1, in formula (1), A is represented by the following formula (2), In the formula (2), R 4 is an alkyl group having 1 or 2 carbon atoms.

3. The composition according to claim 1 or 2, wherein the polymer is a random copolymer.

4. The composition according to claim 1 or 2, wherein in formula (1), m is 2 or more, and at least a part of R 1 is methyl.

5. The composition according to claim 1 or 2, wherein in the formula (1), R 2 and R 3 at least one of them is methyl.

6. The composition according to claim 1 or 2, wherein the water-soluble active ingredient comprises an ionic substance or a non-ionic substance with a logP value of less than 2.

0.

7. The composition according to claim 1 or 2, wherein the water-soluble active ingredient comprises at least one selected from alkoxysalicylic acid or its salt, 1-piperidinepropionic acid or its salt, vitamin B group or its derivatives, and amino acid or its derivatives.

8. The composition according to claim 1 or 2, wherein the polymer is a percutaneous penetration enhancer for the water-soluble active ingredient.

9. An application, which is an application of a polymer having a structure represented by the following formula (1) as a percutaneous penetration enhancer for a water-soluble active ingredient, In the formula (1), R 1 , R 2 and R 3 are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, A is an alkylene group having 2 to 4 carbon atoms, and m and n are each independently 1.0 to 50, The number average molecular weight of the polymer is 10,000 or less, and The IOB value of the polymer is 0.4 to 1.

8.

10. The application according to claim 9, in formula (1), A is represented by the following formula (2), In the formula (2), R 4 is an alkyl group having 1 or 2 carbon atoms.

11. The application according to claim 9 or 10, wherein the polymer is a random copolymer.

12. The application according to claim 9 or 10, wherein in the formula (1), m is 2 or more, and at least a part of R 1 is methyl.

13. The application according to claim 9 or 10, in the formula (1), R 2 and R 3 at least one of them is methyl.

14. The application according to claim 9 or 10, wherein the water-soluble active ingredient comprises an ionic substance or a non-ionic substance with a logP value of less than 2.

0.

15. The application according to claim 9 or 10, wherein the water-soluble active ingredient comprises at least one selected from alkoxysalicylic acid or its salt, 1-piperidinepropionic acid or its salt, vitamin B group or its derivatives, and amino acid or its derivatives.

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