JP2016172706A - Compositions, cosmetics, and solubilizers - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide compositions in which ellagic acid can be maintained in dissolved state even in a neutral region, the composition thereby enabling the expansion of product configuration simultaneously with the improved efficacy of ellagic acid.SOLUTION: The invention provides compositions containing (A) ellagic acid based compound, (B) one or more kinds of compounds selected from borax, ammonium borate, and boric acid, and (C) water. Preferably, the composition further contains (D) one or more kinds selected from the group consisting of a chelator, amino acid, sugar, a mineral salt, a solvent, a polymer, a pyrrolidone compound, urea, amino alcohol, and an ammonium salt. More preferably, the (D) is at least one kind of a chelator containing a nitrogen atom, amino acid, a pyrrolidone compound, urea, amino alcohol, and an ammonium salt.SELECTED DRAWING: None

Description

  The present invention relates to compositions, cosmetics and solubilizers.

  Since ellagic acid, which is frequently used in cosmetics as a whitening component, is poorly water-soluble, its transdermal absorbability is improved by various methods. For example, Patent Document 1 describes a technique for improving the transdermal absorbability by increasing the solubility of an ellagic acid compound by containing an ellagic acid compound and a nitrogen-containing polymer compound. Patent Document 2 discloses that the composition containing an ellagic acid compound and an alkali metal salt thereof contains a compound selected from glycolic acid, lactic acid, malic acid, and salts thereof, thereby dispersing the water dispersibility of the ellagic acid compound. A technique for improving the transdermal absorbability is described.

JP 2002-348205 A JP-A-9-208421

  According to the technique described in Patent Document 1, the ellagic acid compound can be dissolved in a region of pH 7.5 or higher, but in the pH region lower than pH 7.5, which is optimal as a cosmetic, The compound could not be kept in solution. According to the technique described in Patent Document 2, the dispersibility of the ellagic acid-based compound in the composition can be improved, but the solubility cannot be improved.

  Due to the above circumstances, the application methods of ellagic acid compounds to products are limited, and the preparation forms containing ellagic acid compounds that have been commercialized so far are only high-viscosity preparations (creams and gels). In addition, the whitening effect was insufficient.

  An object of the present invention is to provide a composition that can keep an ellagic acid compound in a dissolved state even in a neutral region, thereby improving the effectiveness of the ellagic acid compound and expanding the product form. And

  The inventors of the present invention have made extensive studies to achieve the above object. As a result, by adding borax, ammonium borate, or boric acid to the composition containing ellagic acid compound and water, the ellagic acid compound can be kept in a dissolved state even in a neutral region. The present inventors have found that the absorbability of acid compounds can be improved. The present invention is based on such novel findings.

The present invention provides the following [1] to [7].
[1] (A) an ellagic acid compound,
(B) one or more compounds selected from borax, ammonium borate and boric acid;
(C) water and
A composition comprising
[2] The composition according to [1], further comprising (D) at least one selected from the group consisting of a chelating agent, an amino acid, a sugar, an inorganic salt, a solvent, a polymer, a pyrrolidone compound, urea, an amino alcohol, and an ammonium salt. object.
[3] The composition according to [2], wherein (D) contains at least one of a chelating agent containing a nitrogen atom, an amino acid, a pyrrolidone compound, urea, an amino alcohol, and an ammonium salt.
[4] A cosmetic comprising the composition according to any one of [1] to [3].
[5] A solubilizer comprising (B) one or more compounds selected from borax, ammonium borate and boric acid, and (C) water, solubilizing an ellagic acid compound.
[6] The control according to [5], further including (D) one or more selected from the group consisting of a chelating agent, amino acid, sugar, inorganic salt, solvent, polymer, pyrrolidone compound, urea, amino alcohol, and ammonium salt. Solubilizer.
[7] The solubilizer according to [6], wherein (D) contains at least one of a chelating agent containing a nitrogen atom, an amino acid, a pyrrolidone compound, urea, an amino alcohol, and an ammonium salt.

  According to the present invention, it is possible to provide a composition that can keep an ellagic acid compound in a dissolved state even in a neutral region, thereby improving the effectiveness of the ellagic acid compound and expanding the product form. Can do.

  The composition of the present invention comprises (A) an ellagic acid compound [(A) component], (B) one or more compounds selected from borax, ammonium borate and boric acid [(B) component], ( C) water [component (C)]. The composition of the present invention comprises (D) one or more [(D) component] selected from the group consisting of a chelating agent, amino acid, sugar, inorganic salt, solvent, polymer, pyrrolidone compound, urea, amino alcohol and ammonium salt. Further, it may be included. Hereinafter, each component will be described.

[(A) component]
The component (A) is an ellagic acid compound. A whitening action can be imparted to the composition by including the component (A). Examples of the ellagic acid compound of component (A) include compounds represented by the following formula (2) and derivatives thereof.

[In the above formula (1), R ¹ , R ² , R ³ and R ⁴ are each a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, an acyl group having 1 to 20 carbon atoms, or — (C _m H _2m — O) _n- H (where m is 2 or 3, n is an integer of 1 or more) or a sugar residue represented by the following formula (2), and they are the same May be different from each other. R ⁵ represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 8 carbon atoms. ]

R ¹ , R ² , R ³ and R ⁴ are each a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, an acyl group having 1 to 20 carbon atoms, — (C _m H _2m —O) _n —H (wherein m is 2 or 3, and n is an integer of 1 or more) or a sugar residue represented by the above formula (2). When R ¹ , R ² , R ³ and R ⁴ are alkyl groups, specific examples thereof include a methyl group, an ethyl group, a propyl group, etc. Among them, a methyl group and an ethyl group are preferable. When R ¹ , R ² , R ³ and R ⁴ are acyl groups, specific examples thereof include an acetyl group and a propionyl group. When R ¹ , R ² , R ³ and R ⁴ are — (C _m H _2m —O) _n —H, specific examples thereof include a polyoxyethylene group and a polyoxypropylene group, and n is 5 It is preferably ~ 40. R ¹ , R ² , R ³ and R ⁴ may be the same or different from each other. When R ⁵ is an alkoxy group, specific examples thereof include a methoxy group, an ethoxy group, and a propoxy group, and among these, a methoxy group is preferable.

  Examples of the derivative of the compound represented by the formula (1) include esters and salts. Among these, salts are preferable. Examples of the salt include alkali metal salts such as sodium and potassium, alkaline earth metal salts, ammonium salts, and amine salts. Among these, a part of the phenolic hydroxyl group of ellagic acid is an alkali metal salt. It is more preferable from the viewpoint of solubility and dispersibility.

As the ellagic acid compound, R ^{1 to} R ⁵ in the formula (1) are all hydrogen atoms, R ^{1 to} R ⁴ are hydrogen atoms, methyl groups or ethyl groups, and R ⁵ is a hydrogen atom. A hydroxyl group or a methoxy group is preferable. Specifically, ellagic acid, 3,4-di-o-methyl ellagic acid, 3,3′-di-o-methyl ellagic acid, 3,3 ′, 4-tri-o-methyl ellagic acid, 3,3 ′, Preference is given to 4,4′-tetra-o-methyl-5-methoxyellagic acid, 3-ethyl-4-methyl-5-hydroxyellagic acid, amritoside and salts thereof.

Ellagic acid compounds can be used singly or in appropriate combination of two or more. The amritoside is obtained by replacing R ¹ with a sugar residue represented by the above formula (2) and R ^{2 to} R ⁵ with hydrogen atoms in the above formula (1).

  Ellagic acid-based compounds include strawberry, cod (Caesalupinia Spinosa), eucalyptus (Eucalyptus), apple, poisonous eel (Koreaia japonica), radiata pine, bearberry, pomegranate, anmaroc, cucumber, enfuyo, geijicha, coconut juju, Kenjin, Kunaka, Sankyu Kyukon, Sankyu Kyu, Syufu Boku, Senkutsusai, Sugirou Kansou, Daihi Sou, Domo Anyo, Haouben, Banseki Ryukan, Bansekiyuhi, Boka, Moshokushi, Yew Seikan, Yakusei Hyukan From natural products such as bansekiryoyo, ukukubokukonpi, sidkon, chinsaw, genus shoko, for example, (See Japanese Patent Publication No. 53-14605, etc.).

  The natural product dried pulverized product containing an ellagic acid compound is digested by a normal acidic sulfite method and then immersed in an aqueous solution of sodium hydroxide or sodium carbonate (pH of about 10 to 13). After the immersion liquid is collected, an acid such as sulfuric acid or acetic acid is added to the immersion liquid to adjust the pH to about 2 to 8 to obtain a precipitate mainly composed of an ellagic acid compound. The precipitate is collected by centrifugation or the like, and further washed with water to remove impurities, whereby a highly pure ellagic acid compound can be obtained.

  Content of (A) component in a composition becomes like this. Preferably it is 11 mass% or less with respect to the whole mass of a composition, More preferably, it is 6 mass% or less. If the content of the component (A) is too large, an oriform or crystalline precipitate may be generated during storage.

  The lower limit value of the component (A) content in the composition is preferably 0.001% by mass, more preferably 0.01% by mass with respect to the total mass of the composition. If the content of the component (A) is too small, sufficient effectiveness may not be obtained.

[Component (B)]
One or more compounds selected from (B) component borax, ammonium borate, and boric acid are components that can solubilize component (A) and act as Lewis acid in aqueous solution to stabilize ellagic acid. It is presumed to have an effect of

  The amount of borax when borax is used as the component (B) is preferably 1.1 to 2.0 times, more preferably 1.3 to 1.5 times the mass of the component (A). is there. When used in combination with the component (D), the amount of borax can be reduced. In this case, the amount is preferably 0.1 to 2.0 times the mass of the component (A), More preferably, it is 0.2 to 1.5 times. If the amount of borax is too large, the borax will not dissolve in water and precipitates are likely to occur. If the amount of borax is too small, component (A) may not be sufficiently solubilized and component (A) may remain undissolved.

  The amount of ammonium borate when ammonium borate is used as the component (B) is preferably 0.2 to 2.0 times, more preferably 0.3 to 1 times the mass of the component (A). .0 times. When used in combination with the component (D), the amount of ammonium borate can be reduced, and the amount in this case is preferably 0.1 to 2.0 times the mass of the component (A). More preferably. 0.2 times to 1.0 times. If the amount of ammonium borate is too large, a large amount of acid necessary for neutralization is required. If the amount of ammonium borate is too small, the component (A) may not be sufficiently solubilized and the component (A) may remain undissolved.

  The blending amount when boric acid is used as the component (B) is preferably 0.5 times to 5.0 times, more preferably 1.0 times to 4.0 times the mass of the component (A). is there. When there is too much compounding quantity of boric acid, pH will fall significantly and it will become easy to produce a deposit. If the amount of boric acid is too small, precipitates are likely to occur when the pH is lowered.

  When boric acid is used as the component (B), it is preferable to use a base together. Examples of the base include sodium hydroxide, potassium hydroxide, monoethanolamine, monoisopropanolamine, diisopropanolamine, triisopropanolamine, trometamol and the like. Of these, monoisopropanolamine and monoethanolamine are preferred from the viewpoint that the component (A) can be dissolved with a small addition amount and a smaller pH change.

  When a base is used, it is preferably used at a ratio of 0.1 to 3 times the mass of the component (A). If the amount of the base is small, the component (A) cannot be completely dissolved. If the amount is too large, the amount of acid required for pH adjustment increases.

[Component (C)]
Component (C) is water. Examples of the component (C) include tap water, pure water, and purified water. As the component (C), purified water is preferable.

  The amount of component (C) is preferably 10 to 99.5% with respect to the total amount of the composition.

[(D) component]
The composition of the present invention and the solubilizer of the present invention may further contain a component (D). When the component (D) is contained, the stability of the dissolved state can be improved even when the concentration of the component (A) is high. Further, by including the component (D), it is possible to improve the storage stability of the composition (the effect of delaying crystal precipitation).

  The component (D) is one or more compounds selected from the group consisting of chelating agents, amino acids, sugars, inorganic salts, solvents, polymers, pyrrolidone compounds, urea, amino alcohols, and ammonium salts. As the component (D), a compound having a proton acceptor property is preferable, and a nitrogen-containing compound having nitrogen in the structure, specifically, a chelating agent containing a nitrogen atom, an amino acid, a pyrrolidone compound, urea, amino alcohol and ammonium More preferably, it contains at least one of the salts.

  Chelating agents include edetic acid, citric acid, gluconic acid, oxalic acid, tartaric acid, ascorbic acid, succinic acid, malic acid, phytic acid, etidronic acid, phosphoric acid, polyphosphoric acid, metaphosphoric acid, lactic acid, glycolic acid, and these Examples include salt. Of these, edetic acid, citric acid, oxalic acid, tartaric acid, ascorbic acid, succinic acid, and lactic acid and their salts are preferable, and sodium edetate, sodium citrate, sodium tartrate, sodium succinate and the like are more preferable. Yes (see Table 5 below), more preferably a chelating agent containing a nitrogen atom such as sodium edetate. Sodium edetate, sodium citrate, sodium tartrate, and sodium succinate are considered to have a high effect of attracting protons. Conceivable.

  Amino acids include glycine, glutamine, arginine, alanine, lysine, valine, leucine, isoleucine, phenylalanine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine, histidine, and derivatives thereof. . Among these, glycine with less steric hindrance around nitrogen and glutamine, arginine, and lysine having two or more nitrogen molecules in the molecule are particularly preferable. These amino acids are considered to be particularly effective in attracting protons compared to other amino acids.

  Examples of the sugar include disaccharides such as trehalose and sugar alcohols such as sorbitol.

  Examples of the inorganic salt include sodium phosphate, sodium dihydrogen phosphate, ammonium dihydrogen phosphate and the like.

  Examples of the solvent include polyethylene glycol (PEG) (molecular weight: 300 to 10000), propylene glycol (PG), 1,3-butylene glycol, glycerin and ethanol.

  Examples of the polymer include polysaccharides such as xanthan gum, sodium alginate, carrageenan, and chitosan, and celluloses such as hydroxypropyl methylcellulose (HPMC), hydroxyethylcellulose, and methylcellulose. Of these, xanthan gum, sodium alginate, carrageenan and the like are preferable. Polysaccharides such as xanthan gum, sodium alginate, and carrageenan are thought to delay crystal precipitation due to the thickening effect.

  Examples of the pyrrolidone compound include N-methylpyrrolidone and polyvinyl pyrrolidone (PVP). Of these, PVP is preferred.

  Examples of amino alcohol include monoisopropanolamine, diisopropanolamine, triisopropanolamine, monoethanolamine, diethanolamine, and triethanolamine. Of these, triisopropanolamine is preferred.

  Examples of the ammonium salt include ammonium acetate, ammonium carbonate, ammonium hydrogen carbonate, ammonium chloride and the like.

  (D) A component may be used individually by 1 type and may be used in combination of 2 or more type.

  The amount of component (D) is preferably 0.002 to 1 times, more preferably 0.01 to 0.5 times the mass of component (A). If the amount of component (D) is too small, the effect of delaying crystal precipitation is low, and if the amount is too large, precipitates are likely to be formed.

  In the composition of the present invention, in addition to the above components, components used in ordinary external preparations such as surfactants, oils, alcohols, humectants, thickeners, preservatives, antioxidants, A pH adjuster, a fragrance, a pigment, an ultraviolet absorber / scattering agent, vitamins, amino acids, and the like can be appropriately blended as necessary.

  Specific examples of the surfactant include lipophilic glycerol monostearate, self-emulsifying glycerol monostearate, polyglycerol stearate, sorbitan monooleate, sorbitan monostearate (sorbitan monostearate), polyethylene glycol mono Stearate (polyethylene glycol monostearate), polyoxyethylene sorbitan monooleate (polyoxyethylene sorbitan monooleate), polyoxyethylene cetyl ether, polyoxyethylenated sterol, polyoxyethylenated lanolin, polyoxyethylenated beeswax, Nonionic surfactants such as polyoxyethylene hydrogenated castor oil; sodium stearate, potassium palmitate, sodium cetyl sulfate, sodium lauryl phosphate, palmitic Anionic surfactants such as triethanolamine acid, sodium polyoxyethylene lauryl phosphate, sodium N-acyl glutamate; cationic surfactants such as stearyldimethylbenzylammonium chloride and stearyltrimethylammonium chloride; alkylaminoethylglycine hydrochloride solution, lecithin And amphoteric surfactants.

  Oils include castor oil, olive oil, cacao oil, coconut oil, palm oil, tree wax, jojoba oil, grape seed oil, avocado oil, etc .; animal oils such as mink oil, egg yolk oil; beeswax, whale wax Waxes such as lanolin, carnauba wax and candelilla wax; hydrocarbons such as liquid paraffin, squalane, microcrystalline wax, ceresin wax, paraffin wax, petrolatum; lauric acid, myristic acid, stearic acid, oleic acid, isostearic acid, Natural and synthetic fatty acids of behenic acids; natural and synthetic higher alcohols such as cetanol, stearyl alcohol, hexyl decanol, octyl decanol, lauryl alcohol; isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, olei Octyldodecyl, esters such as cholesterol oleate can be exemplified.

  Examples of humectants include polyhydric alcohols such as glycerin, propylene glycol, sorbitol, polyglycerin and dipropylene glycol; NMF components such as amino acids and sodium pyrrolidonecarboxylate; An example is a functional polymer substance.

  Thickeners include natural polymeric substances such as sodium alginate, xanthan gum, aluminum silicate, quince seed extract, tragacanth gum and starch; semi-synthetic polymeric substances such as methylcellulose, hydroxyethylcellulose, carboxymethylcellulose and soluble starch; carboxyvinyl polymer And synthetic polymer substances such as polyvinyl alcohol.

  Examples of preservatives include benzoate, sorbate, dehydroacetate, p-hydroxybenzoate, 2,4,4′-trichloro-2′-hydroxydiphenyl ether, 3,4,4′-trichlorocarbanilide, chloride Examples thereof include benzalkonium, hinokitiol, resorcin, ethanol and the like.

  As an antioxidant, dibutylhydroxytoluene, butylhydroxyanisole, ascorbic acid, etc., and as a pH adjuster, sodium hydroxide, potassium hydroxide, triethanolamine, aqueous ammonia, hydrochloric acid, potassium hydrogen phosphate, citric acid, Examples thereof include succinic acid, triisopropanolamine, diisopropanolamine, 2-amino-2-methyl-1-propanol and the like.

  Examples of the ultraviolet absorber / scattering agent include 2-hydroxy-4-methoxybenzophenone, octyldimethylparaaminobenzoate, ethylhexylparamethoxycynamate, titanium oxide, kaolin, talc and the like.

  Vitamins include vitamin A, vitamin B group, vitamin C, vitamin D, vitamin E, vitamin F, vitamin K, vitamin P, vitamin U, carnitine, ferulic acid, γ-oryzanol, α-lipoic acid, orotic acid and Examples thereof include derivatives thereof.

  Examples of amino acids include glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine, histidine, lysine and derivatives thereof. .

  Here, it is more preferable that the composition of the present invention has a pH of 6 to 7. If necessary, the pH adjuster may be used alone or in combination of two or more to make the pH range. It is desirable. If the pH is too low, the hardly soluble substance may not be sufficiently solubilized, and if it is too high, the feeling of use on the skin may be impaired.

  The composition of the present invention can be used as it is as a final product (for example, food / beverage products, pharmaceuticals, quasi drugs, cosmetics, etc.). Moreover, it can be used as an additive for food and drink, an additive for pharmaceuticals, an additive for quasi-drugs, and an additive for cosmetics.

  The dosage form of the composition of the present invention is not particularly limited. For example, oral administration (eg, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.) and the like can be mentioned.

  The composition of the present invention can be suitably used, for example, as a skin cosmetic. As skin cosmetics, it can be used for creams, milky lotions, lotions, cosmetics, packs, gels, sheets and the like.

[Solubilizer]
In the present invention, the composition containing the component (B) and the component (C) can be used as a solubilizer for solubilizing the component (A). The solubilizer includes (B) one or more compounds selected from borax, ammonium borate, and boric acid, and (C) water, solubilizing the ellagic acid-based compound, (D) One or more selected from the group consisting of chelating agents, amino acids, sugars, inorganic salts, solvents, polymers and nitrogen-containing compounds may further be included.

  The components (B), (C), and (D) in the solubilizer of the present invention are the same as the composition of the present invention, and the component (A) that the solubilizer of the present invention solubilizes is the present invention. This is the same as the component (A) contained in the composition.

[Prescription example]
When the composition of the present invention is used as a skin cosmetic, specific examples of its formulation are as follows, but are not limited thereto. In the following, “%” means “mass%” unless otherwise specified.

(Lotion, serum)
Ellagic acid compound or alkali metal salt thereof 0.01-2%, component (B) 0.001-10%, base 0-4%, chelating agent 0.001-2%, oil content 0-40%, alcohols 0-40%, surfactant 0-10%, humectant 1-30%, thickener 0-5%, antioxidant 0-1%, pH adjuster 0-5%, purified water balance, preservative A composition containing a trace amount, 0 to a trace amount of pigment, and a trace amount of fragrance (total 100%).

(cream)
Ellagic acid compound or alkali metal salt thereof 0.01-2%, component (B) 0.001-10%, base 0-4%, chelating agent 0.001-2%, oil content 1-70%, alcohols Composition containing 0 to 20%, surfactant 0 to 15%, humectant 1 to 30%, pH adjuster 0 to 3%, purified water balance, preservative trace, and fragrance trace (total 100%).

(Milky lotion)
Ellagic acid compound or alkali metal salt thereof 0.01-2%, component (B) 0.001-10%, base 0-4%, chelating agent 0.001-2%, oil 1-40%, alcohols Contains 0-20%, surfactant 0-10%, moisturizer 1-30%, thickener 0-5%, pH adjuster 0-5%, purified water balance, preservative trace, and fragrance trace. Composition (100% total).

(Formulation example 1: lotion)
Ellagic acid 0.5
Borax 0.2
Monoisopropanolamine 0.2
Beeslow 0.5
Ethanol 10
1,3-butylene glycol 5
Polyoxyethylene (30) hydrogenated castor oil 7
Methylparaben 0.2
Citric acid pH adjusting fragrance Trace purified water Balance meter 100.0%

(Formulation Example 2: Cream)
Ellagic acid 0.5
Borax 0.75
Stearic acid 14
Beeswax 2
Liquid paraffin 1
Polyoxyethylene (2) cetyl ether 5
Polyethylene glycol monostearate (25) 5
Propylene glycol 4
Methylparaben 0.2
Citric acid pH adjusting fragrance Trace purified water Balance meter 100.0%

(Formulation Example 3: Latex)
Ellagic acid 0.5
Borax 0.25
Monoisopropanolamine 0.15
Beeslow 0.5
Liquid paraffin 14.5
Jojoba oil 5
Octild decanol 7
Sorbitan monostearate 4
Polyoxyethylene (20) sorbitan monooleate 6
Propylene glycol 5
Methylparaben 0.2
Citric acid pH adjusting fragrance Trace purified water Balance meter 100.0%

EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated more concretely, this invention is not restrict | limited to the following Example at all.
The main raw materials used in Examples and Comparative Examples are as follows.
(A) Component Ellagic acid: (trade name Ellagic acid LT, manufactured by Lion Corporation)
(B) Component Boric acid: Kanto Chemical Co., Ltd., special grade Ammonium borate: (Ammonium borate octahydrate) Wako Pure Chemical Industries, Ltd., special grade Borax: (Sodium tetraborate decahydrate) Kanto Chemical Co., Inc. Company, Special Grade (C) Component Purified Water Other Monoisopropanolamine: Tokyo Chemical Industry Co., Ltd. Aluminum Chloride (III): Kanto Chemical Co., Ltd., Shikachi Class Iron Chloride (II): (Iron Chloride (II) Tetrahydrate) Kojun Pharmaceutical Co., Ltd., special grade sodium silicate: (sodium silicate aqueous solution) Kanto Chemical Co., Ltd., Shikachi grade hydrochloric acid: (1 mol / L hydrochloric acid) Tokyo Chemical Industry Co., Ltd.

(1) Examination of solubility of ellagic acid (preparation method)
Example 1 Ellagic acid, various compounds and purified water were blended in the proportions shown in Table 1, stirred at room temperature using a stirrer and a magnetic stirrer, and then adjusted to pH 6.5 by adding hydrochloric acid. The composition of 1-1 to 1-3 and the composition of Comparative Examples 1-1 to 1-3 were prepared.
(Evaluation method)
The dissolved state of ellagic acid in the composition immediately after the preparation was visually observed and evaluated according to the following evaluation criteria.
(Evaluation criteria)
○: uniformly dissolved ×: precipitation is precipitated

  From the results shown in Table 1, in the compositions of Examples 1-1 to 1-3 containing any one of borax, ammonium borate and boric acid (component (B)), ellagic acid and purified water, pH However, ellagic acid was uniformly dissolved even at 6.5. On the other hand, in the compositions of Comparative Examples 1-1 to 1-3 that did not contain the component (B), precipitation occurred in a state where the pH was 6.5. From these results, it was found that according to the present invention, a composition capable of keeping ellagic acid in a dissolved state at pH 6.5 (pH 7.0 or lower) can be provided.

(2) Evaluation of dissolution stability of ellagic acid when borax is used (preparation method)
Ellagic acid, borax, monoisopropanolamine, and purified water were blended in the proportions shown in Table 2, and stirred at room temperature using a stirrer and a magnetic stirrer. After uniformly dissolving, each composition was prepared by adjusting the pH shown in Table 2 using hydrochloric acid.
(Evaluation method)
Each composition was placed in a vial (SV-20) and stored at room temperature, −5 ° C., and 40 ° C. for 1 month, and then visually observed for the presence of precipitates and evaluated according to the following criteria.
(Evaluation criteria)
○: No precipitate is observed.
Δ: Slight crystalline precipitates are observed (the presence of the precipitates can be confirmed by tilting the vial and passing through light).
X: A crystalline precipitate is remarkably observed (a state where the precipitate is precipitated at the bottom of the vial).

  From the results shown in Table 2, in the compositions of Examples 2-2 to 2-5 containing ellagic acid, borax and purified water and having a pH of 6.0 or more and 7.0 or less, room temperature, −5 ° C., 40 Precipitates were not observed even after storage at 1 ° C. for 1 month. In the composition of Example 2-1 containing ellagic acid, borax, and purified water and having a pH of 5.8, only a small amount of precipitate was observed when stored at 40 ° C. for 1 month, but at room temperature and −5 No precipitate was observed for those stored at ℃. On the other hand, in the composition of Comparative Example 2-1 containing no borax, precipitates were remarkably observed when stored at room temperature, −5 ° C., and 40 ° C. for 1 month at pH 6.5. From these results, it was found that ellagic acid can be kept in a dissolved state even after storage for 1 month at low and high temperatures by including borax.

(3) Evaluation of dissolution stability of ellagic acid when ammonium borate is used (preparation method)
Ellagic acid, ammonium borate, monoisopropanolamine and purified water were blended in the proportions shown in Table 3, and stirred at room temperature using a stirrer and a magnetic stirrer. After dissolving uniformly, each composition adjusted to pH shown in Table 3 using hydrochloric acid was prepared.
(Evaluation method)
Each composition was placed in a vial (SV-20) and stored at room temperature, -5 ° C, and 40 ° C for 1 month, and then visually observed for the presence or absence of precipitates and evaluated according to the same criteria as in (2).

  From the results shown in Table 3, in the compositions of Examples 3-2 to 3-5 containing ellagic acid, ammonium borate and purified water and having a pH of 6.0 or more and 7.0 or less, room temperature, −5 ° C., Precipitates were not observed even after one month of storage at 40 ° C. In the composition of Example 3-1, which contained ellagic acid, ammonium borate and purified water, and had a pH of 5.7, only a small amount of precipitate was observed after being stored at 40 ° C. for 1 month. No precipitate was observed for those stored at ℃. On the other hand, in the composition of Comparative Example 3-1, which did not contain ammonium borate, precipitates were noticeably observed when stored at room temperature, -5 ° C, and 40 ° C for 1 month at pH 6.5. From these results, it was found that by including ammonium borate, ellagic acid can be kept in a dissolved state even after storage for 1 month at low and high temperatures.

(4) Evaluation of dissolution stability of ellagic acid when boric acid is used (preparation method)
Ellagic acid, boric acid, monoisopropanolamine and purified water were blended in the proportions shown in Table 4, and stirred at room temperature using a stir bar and a magnetic stirrer. After dissolving uniformly, the composition adjusted to pH shown in Table 4 using hydrochloric acid was prepared, respectively.
(Evaluation method)
Each composition was placed in a vial (SV-20) and stored at room temperature, -5 ° C, and 40 ° C for 1 month, and then visually observed for the presence or absence of precipitates and evaluated according to the same criteria as in (2).

  From the results shown in Table 4, in the compositions of Examples 4-2 to 4-4 containing ellagic acid, boric acid and purified water and having a pH of 6.0 or more and 7.0 or less, room temperature, −5 ° C., 40 Precipitates were not observed even after storage at 1 ° C. for 1 month. In the composition of Example 4-1, which contains ellagic acid, boric acid, and purified water and has a pH of 5.8, only a small amount of precipitate was observed when stored at 40 ° C. for 1 month. No precipitate was observed for those stored at ℃. On the other hand, in the composition of Comparative Example 4-1 not containing boric acid, precipitates were noticeably observed when stored at room temperature, −5 ° C., and 40 ° C. for 1 month at pH 6.5. From these results, it was found that ellagic acid can be kept in a dissolved state even after being stored for 1 month at low and high temperatures by including boric acid.

(5) Evaluation of dissolution stability of high concentration ellagic acid (preparation method)
Ellagic acid (5%), borax (7.5%), various additives (0.2%) and purified water were blended and stirred at room temperature using a stirrer and a magnetic stirrer. After uniformly dissolving, each composition was prepared by adjusting the pH to 7.0 using hydrochloric acid.
(Evaluation method)
Each composition was placed in a vial (SV-20) and stored at room temperature, −5 ° C., and 40 ° C. for 2 weeks, and then visually observed for the presence of precipitates and evaluated according to the following evaluation criteria.
(Evaluation criteria)
◎: No precipitate is observed ○: Crystalline precipitate is slightly observed (in a state where the presence of the precipitate can be confirmed by tilting the vial and passing through light)

The following were used as additives.
Sodium edetate: (Ethylenediaminetetraacetic acid disodium) Kanto Chemical Co., Ltd., Special grade Sodium citrate: (Trisodium citrate dihydrate) Kanto Chemical Co., Ltd., Special grade Sodium tartrate: (Sodium tartrate dihydrate) Kanto Chemical Special grade sodium succinate: (disodium succinate) Wako Pure Chemical Industries, Ltd. Special grade disodium hydrogen phosphate: (disodium hydrogen phosphate dodecahydrate) Kanto Chemical Co., Ltd., special grade Glycine: (L -Glycine) Tokyo Chemical Industry Co., Ltd., Special Grade Glutamine: (L-Glutamine) Tokyo Chemical Industry Co., Ltd., Special Grade Arginine Hydrochloride: (L-Arginine Hydrochloride) Tokyo Chemical Industry Co., Ltd., Deer Special Grade Lysine: (L-Lysine Hydrochloride) Shio) Wako Pure Chemical Industries, Ltd., Special Grade Urea: Kanto Chemical Co., Ltd., Special Grade Triisopropanolamine: East Kasei Kogyo Co., Ltd. PG: Propylene Glycol Wako Pure Chemical Industries, Ltd., Special Grade Glycerin: Kanto Chemical Co., Ltd., Special Grade PEG 4000: Polyethylene Glycol Junsei Chemical Co., Ltd. Special grade sodium alginate: Kanto Chemical Co., Ltd., Shikachi grade Iota carrageenan: Product name: GENUISCO JJ Sanki Co., Ltd. Xanthan gum: Product name: KELZAN Sanki Co., Ltd. HPMC: Product name 60SH-1500 Shin-Etsu Chemical Co., Ltd. PVP: Product Name: K-90 BASF

  From the results shown in Table 5, in the composition added with sodium edetate, sodium citrate, sodium tartrate, sodium succinate, glycine, glutamine, arginine hydrochloride, lysine, urea, sodium alginate, iota carrageenan, xanthan gum, polyvinylpyrrolidone High concentration of ellagic acid could be dissolved.

(6) Evaluation of transdermal absorbability The transdermal absorbability of dissolved ellagic acid obtained by the present invention was compared with that of dispersed ellagic acid (ellagic acid dispersed in an aqueous solution).
(Preparation of ellagic acid dispersion of Comparative Example 6)
An ellagic acid dispersion was prepared by the following method.
0.5% ellagic acid and 99.5% purified water were mixed, and the mixture was stirred at room temperature using a stirrer and a magnetic stirrer. The amount of ellagic acid in the dispersion of Comparative Example 6 was 0.5% by mass.
(Evaluation test)
(I) Measurement of the amount of ellagic acid permeated through the skin A lab skin (hairless mouse, HR-1, 7 laps, male) was sandwiched and fixed between the donor and receptor of the cell for the percutaneous absorption test. After adding physiological saline on the receptor side and 1 mL of the composition of Example 2-3 and the dispersion of Comparative Example 6 on the donor side, the cell was placed in a water bath and incubated at 37 ° C. for 24 hours with stirring. Thereafter, 2 mL of the receptor solution was sampled, and the amount of ellagic acid that permeated the skin was measured using HPLC (SHIMAZU SPD20A).
(Ii) Measurement of skin absorption of ellagic acid After removing donor liquid and washing lab skin 3 times with pure water (1 minute, 160 rpm) using a shaker, 3 mM EDTA2Na / 50 mM borax aqueous solution / methanol mixture ( 3 mL of 8: 1) was added, and ellagic acid was extracted from the lab skin using a vortex (5 minutes). Thereafter, the amount of ellagic acid absorbed in the lab skin was quantified using HPLC.
The quantification conditions by (i) and (ii) by HPLC are as follows.
Detector: SHIMAZU SPD20A
Column: Inertsil ODS-3
Temperature: 30 ° C
Flow rate: 0.6 ml / min
Addition amount: 100ul
Mobile phase: (3 mM EDTA2Na + 50 mM Borax) aqueous solution / methanol = 8/1
Detection: UV268nm

From the results shown in Table 6, the dissolved ellagic acid (composition of Example 2-3) has higher skin permeability than the dispersed ellagic acid (dispersion of Comparative Example 6), and the skin absorbability is also higher. it was high. From this result, it was found that the effectiveness of ellagic acid can be improved by the present invention.
According to the results of (1) to (6), according to the present invention, ellagic acid is kept in a dissolved state even at a pH of 7.0 or less, thereby improving the effectiveness of ellagic acid and enabling the expansion of the product form. It turns out that it is possible to provide things.

Claims (7)

(A) an ellagic acid compound,
(B) one or more compounds selected from borax, ammonium borate and boric acid;
(C) water and
A composition comprising   (D) The composition according to claim 1, further comprising one or more selected from the group consisting of chelating agents, amino acids, sugars, inorganic salts, solvents, polymers, pyrrolidone compounds, urea, amino alcohols and ammonium salts.   The composition according to claim 2, wherein (D) comprises at least one of a chelating agent containing a nitrogen atom, an amino acid, a pyrrolidone compound, urea, an amino alcohol, and an ammonium salt.   Cosmetics containing the composition as described in any one of Claims 1-3. (B) one or more compounds selected from borax, ammonium borate and boric acid, and (C) water,
A solubilizer that solubilizes ellagic acid compounds.   (D) The solubilizer according to claim 5, further comprising one or more selected from the group consisting of chelating agents, amino acids, sugars, inorganic salts, solvents, polymers, pyrrolidone compounds, urea, amino alcohols and ammonium salts.   The solubilizer according to claim 6, wherein (D) contains at least one of a chelating agent containing a nitrogen atom, an amino acid, a pyrrolidone compound, urea, an amino alcohol and an ammonium salt.