JP5441207B2 - New antioxidants, active oxygen scavengers, cosmetics - Google Patents

Description

  The present invention relates to a novel antioxidant having active oxygen scavenging ability, an active oxygen scavenger, and a cosmetic product containing them.

  In aged skin, lipid peroxide increases, softness and elasticity are lost, wrinkles of the skin increase, and dry and rough skin symptoms are not smooth. As one of the causative substances in which these skin symptoms appear, so-called active oxygen is considered that oxygen in the atmosphere is generated under the influence of ultraviolet rays or enzymes. This active oxygen is said to be generated not only by oxygen entering the body by breathing, but also by intense emotions such as smoking, stress, anger, anxiety and fear, violent drinking and eating.

  Active oxygen includes free radicals such as superoxide and hydroxy radicals, and non-radicals such as singlet oxygen and hydrogen peroxide. If this active oxygen is present inside and outside the body more than necessary, it also acts on normal cells, cell membranes, and DNA to destroy them. It also produces lipid peroxides because it oxidizes lipids. This also induces various diseases such as worsening atopic symptoms, cataracts, middle winds, myocardial infarction, and carcinogenesis. For the living body, it has adverse effects such as cross-linking of collagen fibers, fragmentation of hyaluronic acid, partial cleavage of DNA helix, tissue damage due to generation of chain radicals, resulting in skin wrinkles, loss of elasticity, hair loss, etc. It is said to promote aging of the living body.

  Therefore, suppressing the production of active oxygen is very important for the skin or for maintaining normal tissues in the living body in terms of improving or preventing skin aging. This is an important factor required for food and drink such as skin cosmetics and health foods. Therefore, the search of the substance which has the effect | action which erase | eliminates the active oxygen conventionally generated in the living body has been performed widely.

  Conventionally used substances having such an action include fat-soluble tocopherol (vitamin E) for natural sources, water-soluble ascorbic acid (vitamin C), and BHT (butylhydroxytoluene) for synthetic compounds. , BHA (butylhydroxyanisole) and the like. Some plant extracts have an antioxidant effect, and attempts have been made to prevent skin aging by blending with cosmetics and foods and beverages (see, for example, Patent Documents 1 to 4). .

  However, there are some plant extracts that are concerned about safety, and the active oxygen scavenging ability is not sufficient, or when blended in the base of a skin external preparation such as cosmetics, an effective effect is obtained. There are few things that can satisfy all in terms of action effects and stability, such as having to add a considerably high concentration to obtain, and adding unpleasant odor to the formulation Met.

JP 2003-128569 A Japanese Patent Laid-Open No. 2002-97151 JP 2002-205933 A JP 2003-321337 A

  In the above circumstances, there has been a demand for a novel antioxidant and active oxygen scavenger that is highly safe, has a sufficient function of scavenging active oxygen generated in the living body, and has good applicability to the skin and the like.

  Accordingly, an object of the present invention is to provide a novel antioxidant or novel active oxygen scavenger excellent in antioxidant effect or active oxygen scavenging effect, or a fragrance composition and skin cosmetic containing them. It is in.

（１）
（Ｒは炭素数１〜５のアルキル基）で表される２，６−ジヒドロキシ安息香酸エステル（以下単に「本発明の化合物」と記す場合がある）を有効成分として含有する抗酸化剤、活性酸素消去剤、香粧品であって、特に好ましくは上記一般式（１）におけるＲの炭素数が１（以下、「メチルエステル化合物」と記す場合がある；下記構造式（２））または２（以下、「エチルエステル化合物」と記す場合がある；下記構造式（３））である。

（２）

（３） Thus, as a result of intensive studies in view of the above circumstances, the present inventors have found that a compound represented by the following general formula (1) has an excellent antioxidant effect, and have completed the present invention. That is, the present invention provides the following general formula (1)

(1)
Antioxidant and activity containing 2,6-dihydroxybenzoic acid ester represented by (wherein R is an alkyl group having 1 to 5 carbon atoms) (hereinafter sometimes simply referred to as “the compound of the present invention”) as an active ingredient Oxygen scavengers and cosmetics, particularly preferably the carbon number of R in the general formula (1) is 1 (hereinafter sometimes referred to as “methyl ester compound”; the following structural formula (2)) or 2 ( Hereinafter, it may be described as “ethyl ester compound”; the following structural formula (3)).

(2)

(3)

  Since the compound of the present invention has an excellent antioxidant effect and active oxygen scavenging effect, it is useful for preventing or reducing various problems in living bodies involving oxidation and active oxygen. Furthermore, in cosmetics containing the compound of the present invention, the amount of conventional antioxidants used can be greatly reduced, and the generation of unpleasant odors for cosmetics can be suppressed, preventing oxidation of various raw materials. In addition to suppressing quality deterioration, it has an excellent active oxygen scavenging effect. Therefore, when this cosmetic product is applied to the skin, it has an effect of eliminating active oxygen in the living body, such as preventing rough skin, maintaining skin gloss, elasticity, brightness, and improving wrinkles. Application to skin cosmetics having an excellent prevention effect can also be expected.

（１）
（Ｒは炭素数１〜５のアルキル基）
The compound of the present invention represented by the following general formula (1) has been conventionally available as a synthetic product, but the antioxidant action and active oxygen scavenging action intended by the present invention have not been known at all.

(1)
(R is an alkyl group having 1 to 5 carbon atoms)

  As a synthesis method, it can be easily produced by esterifying γ-resorcinic acid (2,6-dihydroxybenzoic acid), which is known as an intermediate for pharmaceuticals and agricultural chemicals, by a conventional method.

  In addition, the present inventors have found that the compound of the present invention can be isolated by separating and purifying it from extracts such as roses. It has also been found that the compounds of the present invention are present in less than 0.001% in these extracts such as roses (eg rose essential oil).

The method for extracting the compound of the present invention comprises, for example, Rosa damacena in various solvents, that is, liquefied gas (liquid carbonic acid, liquefied propane, liquefied butane, etc.), water, lower alcohols having 1 to 5 carbon atoms (methyl alcohol, ethyl alcohol). Alcohol, propyl alcohol, etc.), hydrous lower alcohols, esters of lower alcohols with 1 〜 5 carbon atoms and fatty acids with 1 〜 5 carbons (methyl acetate, ethyl acetate, butyl acetate, etc.), ketones (Acetone, methyl ethyl ketone, etc.), hydrated esters and ketones, halogenated hydrocarbons (chloroform, dichloromethane, dichloroethane, trichloroethane, etc.), ethers (methyl ether, ethyl ether, tetrahydrofuran, dioxane, etc.), hydrocarbons (Petroleum ether, hexane, etc.) The extract obtained by extraction with a mixture of acid, alkali treatment, column chromatography, distillation, can be obtained by concentration or the like.

  The compound of the present invention is a pure product containing no impurities, has no foul odor, has a faint spicy fragrance, and is easily harmonized with other fragrance materials and raw materials. In addition, unlike other synthetic antioxidants, this compound can be used safely and with peace of mind because some of these compounds are derived from natural products by the above-described extraction method and the like. Furthermore, compared with other existing synthetic antioxidants that do not exist in the natural world, it also matches the natural orientation that demands are increasing recently in the fields of cosmetics, foods and the like.

  In order to effectively use the compound of the present invention as an antioxidant and an active oxygen scavenger, it is not always necessary to purify it to a state in which no impurities are contained at all, and it may be contained as an active ingredient. From the viewpoint of making the antioxidant effect and active oxygen scavenging action more useful, the compound of the present invention is preferably contained in an amount of 0.001% by mass (hereinafter simply referred to as%). More preferably, it is 0.005% or more, More preferably, it is 0.01% or more, Most preferably, it is 0.05% or more.

Further, in order to obtain a cosmetic product having the above-mentioned antioxidant action and active oxygen scavenging action, the cosmetic product contains one or more compounds of the present invention in a total of 0.0001% or more, preferably 0.0005. % Or more, more preferably 0.001% or more, and most preferably 0.005% or more.

Usually, the rose essential oil mix | blended in cosmetics is 0.001 to 10%. Therefore, it cannot be said that only the compound of the present invention contained in a conventional rose essential oil will sufficiently function as a cosmetic product having the antioxidant and active oxygen scavenging functions which are the objects of the present invention.

（２）

（３） Among the compounds of the present invention represented by the general formula (1), a methyl ester compound wherein the alkyl group represented by R in the general formula has 1 carbon atom (the following structure) Formula (2)) and an ethyl ester compound (the following structural formula (3)) in which R has 2 carbon atoms are also preferred.

(2)

(3)

  Known antioxidant raw materials and solvents can be used in the antioxidant, active oxygen scavenger, or cosmetic of the present invention as long as they do not interfere with the compound of the present invention. Examples of the perfume raw material include various hydrocarbons such as limonene, caryophyllene, and pinene; various aldehydes such as acetaldehyde, α-cinnamic aldehyde, citral; various ketones such as maltol, benzylacetone, and damasenone; butano Alcohol, benzyl alcohol, linalol, etc .; various ether oxides, such as geranyl ethyl ether, rose oxide, furfural; ethyl acetate, benzyl acetate -Esters such as linalyl acetate; Various lactones such as γ-decalactone, coumarin and sclareolide; Various hetero compounds such as indol, 2-isopropyl-4-methylthiazol and phenylacetonitrile ; Jasmine absolute, fern wood oil Oris concrete - various natural materials such as theft and the like. Examples of the solvent used include ethanol, dipropylene glycol (also referred to as DPG), benzyl benzoate, water, triacetin, and triethyl citrate.

  Further, in the cosmetics of the present invention, oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, other oily raw materials, polyhydric alcohols such as glycerin, interfaces, etc., unless they interfere with the compounds of the present invention. Commonly used components such as activators and thickeners can be used. Moreover, you may use together well-known antioxidant (vitamin C, vitamin E, etc.), an active oxygen scavenger, etc. as needed.

  The dosage form as a cosmetic product is also arbitrary and can be various. Specifically, ointments, lotions, oils, emulsions, creams, pastes, gels, powders, molding agents, granules, sprays, aerosols, Listed are sheet agents, patches or haptic agents in which a sheet-like substrate is impregnated with a composition containing the roll-on agent and the extract of the present application.

  The cosmetic product in the present invention is a generic name for quasi-drugs and cosmetics referred to in the Pharmaceutical Affairs Law. Specifically, quasi-drugs include mouth fresheners, odor control agents, tempered powders, hair nourishing agents, Hair removal agents, hair dyes, permanent wave agents, bath preparations, medicated cosmetics, medicated toothpastes, etc. can be listed as cosmetic soaps, facial cleansers (cream / paste, liquid / gel, Granules / powder, aerosols, etc.), cosmetics for cleaning such as shampoos and rinses; hair dyes, hair treatments (including creams, mists, oils, gels and other forms and split hair coats) , Hair set (hair oil, set lotion, curler lotion, pomade, tic, bottled oil, hair spray, hair mist, hair liquid, hair foam, hair gel, war -Grease) and other cosmetics for hair; general cream, emulsion (cleansing cream, cold cream, burnishing cream, hand cream, etc.), shave cream (after shaving cream, shaving cream, etc.), lotion (hand lotion, general lotion) ), Cologne, shaving lotion (after shaving lotion, shaving lotion, etc.), basic cosmetics such as cosmetic oils, packs, baby powder, etc .; Makeup cosmetics such as blusher, eyebrows, eyeshadow mascara, general incense, etc.), powder, foundation (cream, liquid, solid, etc.) Perfumes such as perfume, powdered perfume, etc .; gel type, liquid type, ceramic type fragrance, deodorant, deodorant; sunscreen / sunscreen cream, sunscreen / sunscreen lotion, sunscreen / sunscreen oil, etc. Sunscreen / sunscreen cosmetics; nail cosmetics such as nail cream, enamel and enamel remover; eyeliner cosmetics; lip cosmetics such as lipstick and lip balm; oral cosmetics such as toothpaste; bath cosmetics such as bath salt, bath oil, bubble bath Etc. can be enumerated.

  Hereinafter, although this invention is demonstrated based on a test example and an Example, this invention is not limited to these.

Test Example 1: Active oxygen scavenging effect test (DPPH method)
There are various methods for measuring the effect of scavenging active oxygen, but this time, the ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH), an organic radical, was measured. The method is as follows.

  That is, 100 μl / L of Tris buffer solution (pH 7.5, Wako Pure Chemical Industries, Ltd.) in 80 μl, 99.5% methanol (Junsei) was added to each sample solution in 20 μl, 99.5% on a 96-well microplate. After adding 100 μl of 0.5 mmol / L DPPH (Wako Pure Chemicals), whose concentration was adjusted with methanol (Pure Chemical), the mixture was stirred and incubated at room temperature for 20 minutes in the dark.

Thereafter, the absorbance at 517 nm (the absorbance is defined as A) was measured with a spectrophotometer (Multi-Spectrophotometer Vient XS / Dainippon Sumitomo Pharma). On the other hand, the same operation was carried out with no DPPH added (blank) and no sample added (control), and the obtained absorbance (blank absorbance: B, control absorbance: C) was measured. The active oxygen elimination rate (%) was obtained by the formula.
Active oxygen elimination rate (%) = {1− (A−B) / C} × 100

Similarly, each sample shown in Table 1 was tested. A graph was prepared by plotting the sample concentration on the horizontal axis and the active oxygen elimination rate on the vertical axis, and the concentration at which active oxygen was suppressed by 50% (hereinafter referred to as IC ₅₀ ) was determined from this graph.

The results are shown in Table 1.

  From the above results, the compound of the present invention is more than rosemary oil absolute, which is said to have high antioxidant properties among DL-α − tocopherols and fragrances, which are natural antioxidants that are widely used. It can be seen that it has excellent antioxidant capacity. It can also be seen that 2,6-dihydroxybenzoic acid having a similar structure does not provide much superior antioxidant ability.

Examples 1-5 and Comparative Examples 1-3 (Skin Lotion)
Skin lotions having the compositions shown in Table 2 were prepared according to the following method.

<Preparation method of skin lotion>
The aqueous phase and the alcohol phase are uniformly dissolved, and the aqueous phase and the alcohol phase are mixed, stirred and dispersed to effect solubilization, and then filled into a container. In use, the contents are uniformly shaken and dispersed.

A use test was conducted using the skin lotion prepared above and the following control (skin lotion) to examine the effect of preventing skin aging.
Control (skin lotion)
95% ethyl alcohol 20%
Polyoxyethylene (60 mol) hydrogenated castor oil 3%
Methyl paraoxybenzoate 0.05%
Glycerin 5%
Sodium citrate appropriate amount Ion exchange water Residual

<Test method>
160 female subjects are divided into 20 groups per group, and 8 groups are assigned. Eight kinds of evaluation prescriptions of Examples 1 to 5 and Comparative Examples 1 to 3 are assigned to each group. Each test subject's face is divided into left and right, and the above-mentioned control is applied to one side and the above-mentioned evaluation prescription assigned to the other is applied twice or more every day. A rating was given and evaluated based on the total score. The results are shown in Table 3.

<Criteria>
+3: Very better than control +2: Better than control +1: Slightly better than control 0: No difference -1: Slightly worse than control -2: Poor than control -3: Very worse than control

  As is apparent from Table 3, the skin lotion shown in the examples containing the compound of the present invention as an active ingredient is more effective than the control in terms of preventing rough skin, maintaining skin gloss, elasticity, brightness and improving wrinkles. The ratio (score) to be good was higher than that of the comparative example. It can be seen that the antioxidant action and active oxygen scavenging action of the compound of the present invention are effective, and it is effective for use as a cosmetic for preventing skin aging. In addition, abnormalities such as redness and drying due to the skin lotion according to the example were not recognized.

Examples 6 to 7 and Comparative Examples 4 to 5 (Baths)
Bath compositions having the compositions shown in Table 4 were prepared according to a conventional method. In addition, this bath agent is diluted about 3000 times at the time of use.

A use test was conducted using the bath preparation prepared above and the following control (bath preparation) to examine the effect of preventing skin aging.
Control (bath)
Sodium sulfate 85%
Surfactant appropriate amount Organic dye appropriate amount Dipropylene glycol 0.5%
Sodium bicarbonate appropriate amount

  First, 80 subjects were divided into 20 groups per group, and 4 groups of evaluation prescription baths of Examples 5 and 6 and Comparative Examples 4 and 5 were assigned to each group. The control bath was given to half (10 persons) of each group, the evaluation prescription bath was given to the other half (10 persons), and the bath given at the time of daily bathing for 3 weeks was used. After completion of the evaluation, the control bath and the evaluation prescription bath were given so as to be opposite to the previous evaluation, and the bath was used at the same time for 3 weeks. Then, each subject was given a score for each evaluation item based on the following criteria based on the control bath salt, and the total score was evaluated. The results are shown in Table 5.

<Criteria>
+3: Very better than control +2: Better than control +1: Slightly better than control 0: No difference -1: Slightly worse than control -2: Poor than control -3: Very worse than control

  As is apparent from Table 5, the bath containing the compound of the present invention as an active ingredient is a ratio that is better than the control in terms of preventing rough skin, maintaining skin gloss, elasticity, brightness, and improving wrinkles. The (score) was higher than that of the comparative example. Antioxidant action and active oxygen scavenging action by the compound of the present invention are acting effectively, and it is effective for use as a bathing agent for preventing skin aging. In addition, abnormalities such as redness and drying due to the bath agent according to the example were not recognized.

Formulation Example 1 (Fragrance Formulation Examples 1 and 2, Fragrance Comparison Example 1)
The compound of this invention was mix | blended and the herb system compounding fragrance | flavor of the prescription shown in following Table 6 was produced.

  Perfume Formulation Examples 1 and 2, which are the obtained perfume compositions, do not disturb the fragrance balance even when the compound antioxidant of the present invention is added. It has excellent odor characteristics as well.

Formulation Example 2 (Fragrance Formulation Examples 3 to 4, Fragrance Comparison Example 2)
The compound of this invention was mix | blended and the floral system mixing | blending fragrance | flavor of the prescription shown in following Table 7 was produced.

  Perfume Formulation Examples 3 to 4, which are the obtained perfume compositions, are excellent in the same manner as Perfume Comparative Example 2 which is a conventional floral blended perfume composition without destroying the fragrance balance even when an antioxidant is added. It has a good odor characteristic.

  The compounds of the present invention are useful as active ingredients for antioxidants and active oxygen scavengers. Therefore, it can be suitably used in all fields involving oxidation and active oxygen, for example, cosmetics such as cosmetics for preventing skin aging, foods and drinks, and health foods.

Claims (4)

The following general formula (1)

(1)
An antioxidant or active oxygen scavenger containing a compound represented by (R is an alkyl group having 1 to 5 carbon atoms) as an active ingredient. An antioxidant or active oxygen scavenger containing, as an active ingredient, a methyl ester compound represented by the following structural formula (2) and / or an ethyl ester compound represented by the following structural formula (3).

(2)

(3) Cosmetics containing 0.0001 mass% or more in total of 1 type, or 2 or more types of compounds represented by General formula (1) described in Claim 1 . A total of 0.0001 mass% or more of the methyl ester compound represented by the structural formula (2) described in claim 2 and / or the ethyl ester compound represented by the structural formula (3) described in claim 2. Cosmetics.