JP2786232B2 - New skin external preparation - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a novel external preparation for skin, and more particularly, to a highly safe skin which is excellent in anti-inflammatory effect and wound healing effect, effectively acts to prevent rough skin, and has high safety. It relates to an external preparation.

2. Description of the Related Art Conventionally, it has been attempted to mix an active ingredient such as an aloe extract or an extracted powder thereof with a skin external preparation such as a skin cosmetic for the purpose of anti-inflammation. However, skin cosmetics containing these active ingredients are often not sufficiently exerted by the effects of the active ingredients due to the effects of the base, surfactants, fragrances, and the like, which are simultaneously added, and cause inflammation. It is not always satisfactory as the intended skin external preparation.

Problem to be Solved by the Invention The present invention overcomes the drawbacks of such a conventional external preparation for anti-inflammatory skin, has an excellent anti-inflammatory effect and wound healing effect, and effectively acts to prevent rough skin, It is intended to provide a highly safe external preparation for skin.

Means for Solving the Problems The present inventors have intensively studied to develop a skin external preparation capable of effectively exerting an anti-inflammatory action and a wound healing promoting action without adversely affecting the skin. As a result, a skin external preparation containing an aloe extract or its extracted powder and an ellagic acid-based compound or an alkali metal salt thereof has excellent anti-inflammatory effects and wound healing effects, and effectively acts to prevent rough skin, and It has been found that there is no irritation or sensitization, and the present invention has been completed based on this finding.

That is, the present invention relates to (A) at least one selected from an aloe extract and an extract powder, and (B) a general formula (Wherein R ₁ , R ₂ , R ₃ and R ₄ are a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, a polyoxyethylene or polyoxypropylene residue or a compound represented by the formula Which may be the same or different, and R ₅ is a hydrogen atom, a hydroxyl group or an alkoxy group having 1 to 8 carbon atoms. An external preparation for skin comprising an acid compound and at least one selected from alkali metal salts thereof.

 Hereinafter, the present invention will be described in detail.

In the skin preparation for external use of the present invention, the aloe extract or the extract powder used as the component (A) may be, for example, aloe vera, soap aloe, or kidachi aloe, or a whole plant or a leaf or a jelly portion obtained by removing a leaf bark from a leaf. , Squeezing, crushing, pulverizing, and the like, and purified products and fractionated products by activated carbon treatment for removing colored components that are easily discolored can also be used.

In the skin external preparation of the present invention, the aloe extract or the extract powder may be used alone or in combination of two or more. The content thereof depends on the product form and the frequency of use. The amount is usually selected from the range of 0.005 to 10% by weight, preferably 0.01 to 5% by weight based on the total amount of the external preparation for skin.

In the skin external preparation of the present invention, as the component (B), at least one selected from the ellagic acid compounds represented by the general formula (I) and alkali metal salts thereof is used. Examples of the ellagic acid-based compound include ellagic acid in which R ₁ , R ₂ , R ₃ , R ₄ and R _{5 in the} general formula (I) are all hydrogen atoms, and R ₁ , R ₂ , R ₃ and R ₄ is preferably a hydrogen atom, a methyl group or an ethyl group, and R ₅ is preferably a hydrogen atom, a hydroxyl group or a methoxy group. Examples of the alkali metal salts of these ellagic acid compounds include, for example, sodium salts and potassium salts, and those in which some of the phenolic hydroxyl groups of ellagic acid have become sodium or potassium salts have poor solubility. It is preferable in that it is good.

The ellagic acid-based compound or an alkali metal salt thereof is used to adjust the lipophilicity or hydrophilicity of the external preparation for skin in order to adjust R ₁ , R ₂ , R ₃ and R _{4 in} the general formula (I). Some may be substituted with any group selected from long-chain alkyl groups having up to 20 carbon atoms, polyoxyethylene residues, polyoxypropylene residues and sugar residues represented by the formula (II). Alternatively, R5 may be substituted with a long-chain alkoxy group having up to 8 carbon atoms.

Specific examples of the ellagic acid-based compound and an alkali metal salt thereof include ellagic acid, 3,4-di-o-methylellagic acid,
3,3'-di-o-methylellagic acid, 3,3 ', 4-tri-o-
Methylellagic acid, 3,3 ', 4,4'-tetra-o-methyl-
5-methoxyellagic acid, 3-ethyl-4-methyl-5
Examples thereof include hydroxyellagic acid, amritoside, and alkali metal salts of these compounds.

These ellagic acid compounds are eucalyptus wood (Eucalypt
us), poisonous azalea (Koriaria japonica), radiata pine, bearberry, pomegranate, anmarok, ukyuyou, enfuyou, gaijicha, kakojuyou, miko,
Kiki, Kenjin, Kounaka, Sankyukon, Sankyuyou, Shufuboku, Senkusai, Sougenroukansou, Daihyosou, Doumouanyou, Haouben, Banseki Ryukan, Banseki Ryuh, Bossah, Moshoku, Yutaka, Kanto, Kanto, Kanto From natural products such as sokon, bansekiryuuyou, ukyubokumpi, sidokon, chinshuso, gennoshoko,
For example, it can be easily obtained by the method described in JP-B-53-14605.

The ellagic acid-based compound used in the skin external preparation of the present invention,
As described above, it is widely present in natural products, and its safety is considered to be extremely high.However, when its safety was confirmed just in case, acute toxicity, skin irritation, skin sensitization, mutagenicity In this respect, there was no practical problem, and it was confirmed that the safety was high.

In the external preparation for skin of the present invention, the ellagic acid-based compound and the alkali metal salt thereof may be used alone or in combination of two or more, and the content thereof depends on the product form and the frequency of use. Although it depends, it is usually selected in the range of 0.001 to 20% by weight, preferably 0.005 to 5% by weight based on the total amount of the external preparation for skin.

The skin external preparation of the present invention contains a basic amino acid such as arginine or a monosaccharide such as glucose in order to better disperse the ellagic acid-based compound or an alkali metal salt thereof, preferably 0.001 to 30% by weight. , More preferably 0.005
Can be added at a rate of ~ 20% by weight,
If desired, various components usually used in external preparations for skin, such as oils, water, surfactants, moisturizers, lower alcohols, thickeners, antioxidants, chelating agents, pH adjusters, preservatives Fragrances, pigments, UV absorbers, UV scattering agents, vitamins, amino acids, and the like.

Examples of the oil component include oils and fats such as olive oil, jojoba oil, cacao butter, camellia oil, palm oil, wood wax, grape seed oil, avocado oil, mink oil, egg yolk oil, and hardened oil, whale wax, beeswax, and lanolin. , Carnauba wax, candelilla wax and other waxes, liquid paraffin, ceresin, squalane, microcrystalline wax, paraffin wax, hydrocarbons such as petrolatum, stearic acid, oleic acid, lauric acid, myristic acid, isostearic acid, behenic acid, etc. Fatty acids, alcohols such as cetanol, stearyl alcohol, lanolin alcohol, octyldodecanol, hexyldecanol, myristines isopropyl, butyl stearate, isopropyl palmitate, octyldodecyl myristate, octyldode oleate Le, and the like esters such as cholesterol oleate.

Examples of the surfactant include anionic surfactants such as sodium stearate, sodium cetyl sulfate, polyoxyethylene lauryl ether phosphate, sodium lauryl phosphate, triethanol palmitate, sodium N-acylglutamate, and stearyl dimethylbenzyl chloride. Ammonium, cationic surfactants such as stearyltrimethylammonium chloride, alkylaminoethylglycine hydrochloride solution, amphoteric surfactants such as lecithin, glyceryl monostearate, sorbitan monostearate, sucrose fatty acid ester, propylene glycol monostearate, Polyoxyethylene oleyl ether, polyethylene glycol monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene coconut fatty acid Bruno ethanolamide, polyoxyethylene polyol key propylene glycol, polyoxyethylene castor oil, such as non-ionic surfactants such as polyoxyethylene lanolin.

Examples of the humectant include polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, sorbitol, polyethylene glycol and dipropylene glycol, amino acids, NMF components such as sodium lactate and sodium pyrrolidone carboxylate, hyaluronic acid, and collagen. , Mucopolysaccharides, water-soluble polymer substances such as chondroitin sulfate, etc., as lower alcohols,
For example, ethanol, isopropanol and the like, as a thickener, for example, sodium alginate, xanthan gum, aluminum silicate, quince seed extract, tragacanth gum, natural polymer substances such as starch, methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, soluble starch, cation Semi-synthetic polymer substances such as activated cellulose, and synthetic polymer substances such as carboxyvinyl polymer and polyvinyl alcohol.

Further, as an antioxidant, for example, dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, ascorbic acid, etc., as a chelating agent,
For example, disodium edetate, ethanehydroxydiphosphate, pyrophosphate, hexametaphosphate, citric acid, tartaric acid, gluconic acid, etc., as pH adjusters, for example, sodium hydroxide, triethanolamine, citric acid, sodium citrate , Boric acid, borax, sodium monohydrogen phosphate, and the like. Preservatives include, for example, methyl paraoxybenzoate, ethyl paraoxybenzoate, dehydroacetic acid, salicylic acid, benzoic acid, sorbic acid, benzalkonium chloride, and the like. .

Further, as the ultraviolet absorber, for example, 2-hydroxy-4-methoxybenzophenone, octyldimethylparaaminobenzoate, ethylhexyllamethoxycinnamate, and the like, and as the ultraviolet scattering agent, for example, titanium oxide, kaolin, talc, and the like can be used. For example, vitamin A, vitamin B, 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 derivatives thereof As amino acids, for example, glycine, alanine,
Examples include valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine, histidine, lysine and derivatives thereof. The optional components are not limited to these.

The skin preparation for external use of the present invention can be prepared by appropriately blending the essential components (A) and (B) with these optional components, for example, creams such as hand cream, nutrition cream, massage cream, and lotion. ,lotion,
Skin milk, milky lotion, pack, bath salt, scalp (scalp)
It can be used as various product forms such as treatments for medical use.

Specifically, as a lotion, (A)
It contains 0.01 to 2% by weight of component (B) and 0.01 to 2% by weight of component (B), and optionally contains 2 to 10% by weight of lower alcohol, 0 to 1% by weight of surfactant, 2 to 7% by weight of humectant, pH
A composition containing 0 to 0.2% by weight of a regulator, 77 to 94% by weight of purified water, and trace amounts of preservatives, pigments, and fragrances is used as a cream for skin, as an essential component, component (A) 0.01 to 2% by weight.
And (B) 0.01 to 2% by weight of an ingredient, and 20 to 70% by weight of an oil component, 1 to 7% by weight of a surfactant, 0.1 to 10% by weight of a humectant, 8 to 73% by weight of purified water, and A composition containing a trace amount of preservatives and fragrances, as a lotion,
It contains 0.01 to 2% by weight of component (A) and 0.01 to 2% by weight of component (B) as essential components, and 5 to 10% by weight of lower alcohol, 0.5 to 2% by weight of surfactant, and humectant 2 as optional components. -8% by weight, 0.01-0.05% by weight of antioxidant, 0.02-0.1% by weight of chelating agent, 0.1-1% by weight of pH adjuster, 77-94% by weight of purified water and trace amounts of preservatives, pigments and fragrances The composition contains, as skin milk, 0.01 to 2% by weight of component (A) and 0.01 to 2% by weight of component (B) as essential components, and 20 to 40% by weight of oil as an optional component. A composition containing ５5% by weight, purified water 53-78% by weight and trace amounts of preservatives and fragrances is used as an emulsion, as essential components (A) 0.01-2% by weight and (B) 0.01-2% by weight. Containing, as an optional component, an oil content of 10 to 30% by weight,
Surfactant 1-5% by weight, humectant 2-10% by weight, purified water
Compositions containing 54-86% by weight and trace amounts of preservatives and fragrances are included.

Effect of the Invention The skin external preparation of the present invention contains an aloe extract or an extract powder thereof as an essential component, an ellagic acid compound or an alkali metal salt thereof, and has an anti-inflammatory effect as compared with conventional ones. It has an excellent wound healing effect, works effectively to prevent rough skin, and is also excellent in safety and stability. Therefore, for example, various cosmetic creams, lotions, lotions, serums, milky lotions, packs, powders, lip balms, lipsticks, under makeup for cracks, irritations, rough skin, skin after shaving, scalp after shampoo, etc. It is suitably used as various product forms such as up, foundation, sun care, bath salt, body shampoo, body rinse, and scalp treatment.

EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1, Comparative Examples 1 and 2 Creams having the compositions shown in Table 1 were prepared, and the effect of improving skin roughness was evaluated by the following method.

That is, cream was applied twice a day to the affected area of a cracked or broken patient (10 patients in each group) twice a day for 3 weeks, and the degree of healing was evaluated according to the following criteria. The results are summarized in Table 2.

Judgment criteria Excellent: Cracks and nicks became almost inconspicuous.

Efficient: Cracks and nicks are much shallower and smoother overall.

Moderately effective: cracks and cracks slightly shallower.

Ineffective: No change As is clear from the results in Table 2, the cream containing the aloe extract powder and ellagic acid (Example 1) contained only the aloe extract powder (Comparative Example 2) or only ellagic acid (Comparative Example 1). It can be seen that cracks and irritations are improved as compared with the cream.

During and after use of the cream, no skin irritation or allergic reaction was observed, confirming that the cream was extremely safe. It was also confirmed that the cream had no discoloration over time and had high stability.

Example 2 and Comparative Examples 3 and 4 25.0 g of commercially available ellagic acid (manufactured by Kikkoman Corporation) was added to 500 g of purified water, and dispersed with stirring.
Add and dissolve 500 g of 1.0N sodium hydroxide aqueous solution,
Further, 5.0 g of activated carbon was added, and the mixture was stirred at room temperature for 30 minutes. Then, the suspension was filtered under reduced pressure to obtain a reddish brown filtrate, to which concentrated hydrochloric acid was added dropwise to adjust the pH to 7.0,
A precipitate was deposited. After centrifugation (8000 rpm, 10 minutes), the precipitate was collected, washed with water and ethanol, and dried to obtain 24.2 g of sodium salt of ellagic acid.

Next, a cream having the composition shown in Table 3 was prepared (adjusted to a pH of 5.0 to 5.5 with citric acid) using the sodium ellanate (treatment pH 7.0) thus obtained. The anti-inflammatory effect was evaluated by the following method.

That is, 4 week old Wistar male rats (SP
F, 5 mice in each group) were inoculated subcutaneously with 0.05 ml of a 1% γ-carrageenin (Sigma) solution under the right hind footpad, and immediately gauze (2.5 × 2.5) coated with 1 g of the cream shown in Table 3 c
In m), the edema was wrapped in the hind limb and the edema degree was calculated by a volume method 2 hours later, and the edema inhibition rate was calculated by the following equation. The results are summarized in Table 3.

Vo: Volume before carrageenan inoculation V: Volume after 2 hours after carrageenan inoculation Eb: Edema rate of control group (no treatment) Et: Edema rate of test group As is clear from the results in Table 3, a cream containing the aloe extract and sodium ellagate (Example 2)
Shows that the anti-inflammatory effect is superior to that of a cream containing only the aloe extract (Comparative Example 4) or sodium ellanate (treatment pH 7.0) 3 (Comparative Example).

Example 3, Comparative Examples 5 and 6 Emulsions having the compositions shown in Table 4 were prepared, and the wound healing effect was evaluated by the following method.

That is, 5 week old Wistar male rats (SP
F, 7 rats in each group) under Nembutal anesthesia, after extensively cutting the back hair, disinfecting with alcohol, and creating a sharp linear wound of 4 cm in the center of the rat along the midline with a scalpel, It was sutured with a Michelle needle every 1 cm.

After making the wound, the above emulsion was continuously applied to the wound part twice a day in 0.3 ml portions for 8 days. On the ninth day, the rats were killed with chloroform, the wound skin was peeled off, the subcutaneous tissue was removed, and three 1-cm-wide skin pieces orthogonal to the wound line were prepared from each rat using a razor. About Model 11
The tension (g / cm; Tensile Stren) required for the wound skin piece to be separated using a universal measuring instrument (manufactured by Instron)
gth value), and the average value was used as an index of the wound healing rate.

The results are summarized in Table 4. The results are shown as relative values when the control group (untreated) is set to 100.

As is clear from the results in Table 4, the emulsion containing the aloe-extracted powder and potassium ellagate (Example 3) contained only the aloe-extracted powder (Comparative Example 6) or only potassium ellagate (treatment pH 6.0). It can be seen that the wound healing effect was superior to that of the emulsion containing (Comparative Example 5).

That is, it was found that the external preparation for skin containing the aloe extract of the present invention or the extracted powder thereof and the ellagic acid-based compound has excellent anti-inflammatory effects and wound healing effects, and effectively acts to prevent rough skin.

Example 4 Various skin external preparations of the present invention are shown below.

Essence Sodium salt of ellagic acid (treatment pH 5) 0.5wt% Aloe extract powder 0.1 Silicone KF56 1.0 POE (40) glyceryl trioleate 1.0 Glycerin 8.0 Ethanol 5.0 Hydroxyethyl cellulose 0.2 Fragrance Fine amount Purified water Balance Lotion 1 3,3 ', 4 -Tri-o-methylellagic acid 0.1wt% Aloe extract (15% solution) 1.0 Propylene glycol 5.0 Ethanol 7.0 Methylparaben 0.1 Sodium citrate 0.02 Fragrance Purified water Balance Emulsion A. Oil phase Silicon KF56 2.0wt% Isopropyl palmite Tate 3.0 POE (20) POP (2) Cetyl alcohol ether 1.0 Ethyl paraben 0.1 B. Aqueous phase ellagic acid sodium salt (treatment pH 6.5) 1.0 wt% Aloe extract powder 0.5 Glycerin 3.0 Hydroxypropyl cellulose 0.2 Ethanol 5.0 Purified water Balance C. Appropriate amount of fragrance Mix above Formulations A and B at 70 ℃ After dissolution, A was added to B and emulsified uniformly. Add more C, cool,
An emulsion was prepared.

Cosmetic cream A. Oil phase Liquid paraffin (# 70) 5.0 wt% Squalane 5.0 Cetostearyl alcohol 5.0 Reduced lanolin 3.0 Honey roe 2.0 Glycerin monostearate 1.5 POE (20) Sorbitan monolaurate 2.0 Propyl paraben 0.1 B. Water Phase part Sodium ellagate (treatment pH 6.0) 0.2 wt% Aloe extract powder (activated carbon treatment) 1.0 1,3-butylene glycol 5.0 methyl lavene 0.2 Purified water Balance C. Fragrance fine amount Formulations A and B at 70 ° C After mixing and dissolving, A was added to B and emulsified uniformly. Add more C,
Upon cooling, a cream was prepared.

All of the above compositions exhibited good anti-inflammatory effects and wound healing effects, and were also effective against rough skin.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 35/78 ADT A61K 35/78 ADT // (A61K 35/78 31:70) (A61K 35/78 31: 365) (58 ) Surveyed field (Int.Cl. ⁶ , DB name) A61K 7/00-7/50

Claims (1)

(57) [Claims] (A) at least one selected from an aloe extract and an extract powder, and (B) a general formula (Wherein R ₁ , R ₂ , R ₃ and R ₄ are a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, a polyoxyethylene or polyoxypropylene residue or a compound represented by the formula Which may be the same or different, and R5 is a hydrogen atom, a hydroxyl group or an alkoxy group having 1 to 8 carbon atoms. A novel external preparation for skin, comprising a system compound and at least one selected from alkali metal salts thereof.