TWI392518B - Cosmetics containing diethylene glycol diol diol - Google Patents

Description

Cosmetic containing diethylene linoleate diethylene glycol oligomer

The present invention relates to a cosmetic containing dimer dilinoleate diethylene glycol oligomer ester.

In recent years, with the changes in the environment, patients with allergic diseases such as atopic dermatitis, or people with skin allergies have gradually increased. Because these people's skin is prone to allergies, redness caused by cosmetics and other items often occurs. Symptoms, such as itching, and the demand for less stimulating cosmetics, so the market needs to provide a new, excellent ingredients to alleviate such stimuli.

At present, it has been disclosed that a trehalose monomer fatty acid ester (Patent Document 1: JP-A-10-45560), a perfluoroalkyl group and a polyoxyalkylene (polyoxyalkylene) are branched as an anthracene resin (Patent Document 2: Kaiping No. 6-199629), a skin irritation suppressant such as a surfactant; a glucose derivative such as phenethyl-α-glycoside or phenethyl-β-glycoside (Patent Document 3: Japanese Patent Publication No. 8-283121, for example, as an alcohol-stimulated tempering agent; for example, a polyalkanol (Patent Document 4: JP-A-2002-212024), as a stimulating agent for a fat-soluble drug; Ethanol and water (Patent Document 5: JP-A-H05-255118) are used as a stimulator for skin external preparations. However, there is a study on the safety of an oil agent which accounts for a large proportion of the cosmetic base (Non-Patent Document 1: Sugiyama, Ota, "Skin Irritability Evaluation of Cosmetic Oily Raw Materials", Japan Skin Association Series, Japan Industrial Skin Hygiene Association, February 1999, Vol. 41, p. 136-142), but has not been studied for its stimulating effect.

In the case of a cosmetic product containing a dimer acid ester, it has been examined for its glossiness, water retention, touch, adhesion to skin and hair, and improvement in contact with the patent document 6 (JP-A-2004-277285). The persistence of the senses and the ease of finishing the hair. However, in Patent Document 6, there is no discussion on the stimulation mitigation effect.

[Patent Document 1] Japanese Laid-Open Patent Publication No. Hei No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. Japanese Patent Publication No. Hei 5-255118

[Non-Patent Document 1] Sugiyama and Ota, "Skin Irritability Evaluation of Cosmetic Oily Raw Materials", Japan Skin Association Series, Japan Industrial Skin Health Association, February 1999, Vol. 41, p.136-142

The object of the present invention is to find an oil agent which is excellent in stimulating and relaxing, and further provides a cosmetic containing the oil.

The main constitution of the present invention is as follows: (1) A cosmetic containing a diethylene linoleate diethylene glycol oligomer.

(2) The cosmetic material according to (1), wherein the ratio of the dimerized linoleic acid and the diethylene glycol in the dimerized linoleic acid diethylene glycol ester oligomer is dimerized linoleic acid: Ethylene glycol = 0.5 mole: 1.0 mole to 0.8 mole: 1.0 mole.

(3) The cosmetic material according to (1), wherein the ratio of the dimerized linoleic acid and the diethylene glycol in the dimerized linoleic acid diethylene glycol oligomer is dimerized linoleic acid: Ethylene glycol = 0.5 mole: 1.0 mole.

(4) The cosmetic material of (1), the dimerized linoleic acid diethylene glycol oligomer has a viscosity at 25 ° C of 2,500 ~ 4,500 mPa. s.

(5) The cosmetic material according to any one of (1) to (4), wherein the dimerized linoleic acid diethylene glycol ester oligomer is a skin irritation mitigating component.

(6) The cosmetic according to any one of (1) to (5), which is a moisturizing cosmetic for the face or the body.

(7) The cosmetic according to any one of (2) to (6), which contains 5 to 20% by mass of a diethylene linoleic acid diethylene glycol ester oligomer.

(8) An oil composition for a cosmetic containing diethylene linoleate oligomer, wherein the ratio of dimer linoleic acid to diethylene glycol is dimerized linoleic acid: two Glycol = 0.5 mole: 1.0 mole to 0.8 mole: 1.0 mole.

According to the present invention, the following effects can be achieved.

1. It is possible to provide an oil agent which is excellent in stimulating and relaxing effect, and a cosmetic containing the oil agent.

2. Since the cosmetic of the present invention has an excellent stimulating and relaxing effect, it is possible to suppress the segregation and destruction of the skin by the stimulating substance by using the cosmetic of the present invention. In addition, by suppressing the damage of the skin to improve the roughness of the skin and protecting the skin, it is possible to provide a cosmetic which is excellent in skin roughness and moisturizing effect.

3. By using the cosmetic of the present invention, skin aging can be maintained by an excellent moisturizing effect against the aging phenomenon caused by drying caused by skin irritation, and thus aging can be prevented.

4. Since the dimer linoleic acid diethylene glycol oligomer used in the cosmetic of the present invention has low viscosity, sticky feeling and glare, it is suitable for use in moisturizing such as lotion, cream, etc. Use a cosmetic.

Hereinafter, the present invention will be described in detail.

The dimerized linoleic acid diethylene glycol ester oligomer of the present invention is obtained by esterifying dimer linoleic acid with diethylene glycol.

<Dimerized linoleic acid>

Dimerized linoleic acid is a dibasic acid generally called dimer acid, and two molecules of linoleic acid [(9Z, 12Z)-octadecane-9,12-dienoic acid] are not A 2-mer of linoleic acid after polymerization of a saturated fatty acid. Among the products of the linoleic acid polymerization, in addition to the 2-mer of linoleic acid, unreacted linoleic acid and a terpolymer are contained, and even a highly polymerized linoleic acid copolymer is contained. Among them, the content of the linoleic acid dimer can be increased to 90% by mass or more by a method of molecular distillation. Further, hydrogen can be added to the unsaturated combination of the obtained linoleic acid 2 polymer to stabilize it. The addition of these linoleic acid 2 polymers to hydrogen is generally referred to as hydrogenated dimer acid. The dimerized linoleic acid diethylene glycol ester oligomer of the present invention, the dimerized linoleic acid used for the synthesis thereof, although any of the above dimer acids and hydrogenated dimer acids may be used, but if it is stabilized by oxidation From a sexual point of view, it is more appropriate to use a hydrogenated dimer acid. As the hydrogenated dimer acid, a commercially available product such as PRIPOL 1006, PRIPOL 1009, PRIPOL 1025 or the like produced by UNIQEMA Co., Ltd. can be used.

<diethylene glycol>

Diethylene glycol is a compound represented by the chemical formula of O(CH ₂ CH ₂ OH) ₂ and is marketed as an organic synthetic raw material.

The dimerized linoleic acid is polymerized with diethylene glycol to carry out an esterification reaction, and a dimerized linoleic acid diethylene glycol ester oligomer can be obtained by copolymerization. The esterification method is not specifically defined, for example, no catalyst or p-toluenesulfonic acid, sulfuric acid, hydrochloric acid, methanesulfonic acid or the like as a catalyst, no solvent or toluene, hexane, heptane. The reaction can be carried out at a temperature of 50 to 260 ° C as a solvent.

The ratio of dimerized linoleic acid to diethylene glycol constituting dimer linoleic acid and diethylene glycol is suitably 0.5 mol: 1.0 mol to 0.8 mol: 1.0 mol. When dimerized linoleic acid: diethylene glycol is 0.5 moles: 1.0 mole, an oligomer is formed, which is centered on the combination of diethylene glycol and dimeric linoleic acid at both ends. . When dimerized linoleic acid: diethylene glycol is 0.8 mol: 1.0 mol, an oligomer will be formed, which is obtained by ester bonding of 4 dimerized linoleic acid and 5 diethylene glycol. The substance is distributed as a center.

In either case, diethylene glycol is much more abundant than dimerized linoleic acid, so there is almost no remaining carboxyl group, and the functional groups remaining at the end of the oligomer are almost all hydroxyl groups. When the molar ratio of dimerized linoleic acid to diethylene glycol is close to 1, the degree of polymerization becomes large, and the viscosity of the oil agent is also enhanced, which is not preferable. Further, if the molar concentration of dimerized linoleic acid is more than that of diethylene glycol, the remaining functional group will become a carboxyl group, which is not preferable from the viewpoint of safety.

In particular, the ratio of dimerized linoleic acid and diethylene glycol is dimerized linoleic acid: diethylene glycol = 0.5 mol: 1.0 mol, and the viscosity at 25 ° C is 2,500 to 4,500 mPa‧s. The diethylene linoleic acid diethylene glycol oligomer can be found to have a small skin permeability, a stimulating effect, and a percutaneous evapotranspiration inhibition effect, thereby confirming that the effect of preventing skin roughness is high. For this effect, there is indeed a significant difference even when compared with similar dimerized linoleic acid diethylene glycol oligomers.

Further, in Patent Document 1, although a cosmetic material containing various dimerized linoleic acid diethylene glycol oligomers was examined, no stimulating effect was discussed. In Patent Document 6, a dimerized linoleic acid diethylene glycol ester oligomer (dimer acid: diethylene glycol = 1:0.5) / mixed ethanol (docosanol: isostearyl alcohol) is disclosed. : phytol = 9:1:1) ester, but with respect to the compounding ratio of the present invention, that is, dimerized linoleic acid: diethylene glycol = 0.5 mole: 1.0 mole to 0.8 mole: 1.0 mole two The poly-linoleic acid diethylene glycol oligomers have not been disclosed, and their polarities are different, and their physical properties and usability are completely different.

The amount of the dimerized linoleic acid diethylene glycol ester oligomer to be blended in the cosmetic of the present invention is not particularly limited, but is preferably 0.1 to 95% by mass based on the total amount of the cosmetic. When the cosmetic is a moisturizing cosmetic, the amount of the dimerized linoleic acid diethylene glycol oligomer is suitably from 0.1 to 40% by mass, and more preferably from 5 to 20% by mass. When the blending amount is 40% by mass or more, the stickiness is too strong and it is not suitable as a cosmetic; if it exceeds 20% by mass, the stickiness becomes strong; however, if the blending amount is 5% by mass or less, the stimulus is stimulated. The relaxation effect is weakened, and when it is 0.1% by mass or less, there is almost no irritating effect.

The cosmetic (including quasi-drug) of the present invention may, for example, be a lotion, an emulsion, a cream, a hand cream, a body lotion, a beauty lotion, a sunscreen lotion, a foundation, a lipstick, or the like. Since the cosmetic of the present invention has a remarkable stimulating effect and a skin roughness preventing effect, it is very suitable for use in a moisturizing cosmetic. Examples of the moisturizing cosmetic include lotions, lotions, creams, hand creams, body lotions, and cosmetic liquids.

The cosmetic of the present invention may contain, for example, vegetable oils, fats and oils, higher fatty acids, higher alcohols, anionic surfactants, cationic surfactants, amphoteric surfactants, etc., depending on the use, purpose of use, dosage form, and the like. Nonionic surfactants, preservatives, sugars, metal ion blocking agents, powder components, UV absorbers, UV disinfectants, moisturizers such as hyaluronic acid, perfumes, pH adjusters, etc. In addition, it may also contain vitamins, skin activators, blood circulation promoters, beneficial bacteria control agents, active oxygen scavengers, anti-inflammatory agents, whitening agents, fungicides and other medicinal ingredients, physiologically active ingredients.

As the fats and oils, examples include pile oil, evening primrose oil, Hawaiian stone fruit (Macadamia nut), olive oil, rapeseed oil, corn oil, sesame oil, jojoba oil, germ oil, wheat germ oil, tricapry glycerol, etc. Liquid fats, cocoa butter, coconut oil, hardened coconut oil, palm oil, palm kernel oil, wood wax nuclear oil, hardened oil, hardened castor oil and other solid fats, beeswax, candied wax, cotton wax, wax, Waxes such as lanolin, acetic acid lanolin, liquid lanolin, sugar cane wax, mobile paraffin, squalene, eucalyptus oil, microcrystalline wax, and the like.

As the higher fatty acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, and docosahexaenoic acid may be mentioned. Acid (docosahexaenoic acid) (DHA), eicosapentaenoic acid (EPA), and the like.

Examples of the higher alcohol include linear alcohols such as lauryl alcohol, stearyl alcohol, cetyl alcohol, and cetostearyl alcohol; monostearyl glycerin ether, lanolin alcohol, and cholesterol. (cholesterol), phytosterol, octyl dodecanol, and the like.

Examples of the anionic surfactant include fatty acid salts such as sodium laurate, higher alkyl sulfate salts such as sodium lauryl sulfate, and alkyl ether sulfates such as POE triethanolamine. - Acylsarcosine, sulfosuccinate, N-decylamino acid salt, and the like.

The cationic surfactant may, for example, be an alkyltrimethylammonium salt such as stearyl trimethylammonium chloride, benzalkonium chloride or benzethonium chloride.

Examples of the amphoteric surfactant include a betaine-based surfactant such as an alkyl betaine or an amidobetaine.

Examples of the nonionic surfactant include sorbitan fatty acid esters such as sorbitan monooleate and hardened castor oil derivatives.

Examples of the preservative include methyl paraben, ethyl paraben, and the like.

Examples of the metal ion blocking agent include EDTA acid salts such as disodium ethylenediamine tetraacetate, EDTA acid, and EDTA sodium salt.

In order to suppress the stickiness and increase the color, examples of the powder component include talc, kaolin, mica, silicon, zeolite, polyethylene powder, polystyrene powder, cellulose powder, inorganic white pigment, inorganic red pigment, and titanium dioxide. Covering mica, titanium dioxide coated talc, pigmented titanium dioxide coated mica and other pearlescent pigments, red 201, red 202 and other tar dyes.

Examples of the ultraviolet absorber include p-aminobenzoic acid, phenyl salicylate, isopropyl p-methoxycinnamate, and p-methoxy cinnabar. Octyl p-methoxycinnamate, 2,4-dihydroxybenzophenone, and the like.

Examples of the ultraviolet ray release agent include titanium oxide, talc, carmine, bentonite, kaolin, and zinc oxide.

Examples of the humectant include xylitol, maltitol, maltose, sorbitol, glucose, fructose, sucrose, lactose, sodium chondroitin sulfate, sodium hyaluronate, and sodium lactate. , pyrrolidone carboxylic acid, cyclodextrin, and the like.

Examples of the medicinal ingredient include vitamin A, vitamin A such as retinol, vitamin B2 such as riboflavin, B6 such as pyridoxine hydrochloride, pantothenic acid such as calcium pantothenate, vitamin D2, and cholecalciferol. (cholecalciferol) and other vitamins such as vitamin D, α-tocopherol, tocopherol acetate, DL-α-tocopherol nicothinate, and the like.

Other examples include skin activators such as royal jelly and beech extract, capsaicin, zingerone, cantharides tincture, fish fat, caffeine, tannic acid, γ-oryzanol, and the like. Blood circulation promoter, glycyrrhizic acid derivative, glycyrrhetinic acid derivative, azulene anti-inflammatory agent, arginine, serine, leucine A leucine), an amino acid such as tryptophan, a maltose sucrose condensate of a beneficial bacteria controlling agent, or a lysozyme chloride.

In addition, it can also be combined with, for example, chamomile extract, parsley extract, red wine yeast extract, grapefruit extract, honeysuckle extract, rice extract, grape extract, hop extract, rice bran extract, alfalfa extract, Astragalus extract, Coix seed extract, Swertia japonica extract, Melilotus officinalis extract, bich extract, peony extract, Saponaria officinalis extract, loofah extract , red pepper extract, lemon extract, gentian extract, perilla extract, aloe extract, rosemary extract, sage extract, thyme extract, tea extract, algae extract, cucumber Various extracts such as extract, clove extract, horse chestnut extract, hamamelis extract, mulberry extract, and the like.

(Example 1)

Diethylene linoleic acid diethylene glycol ester oligomer (dimerized linoleic acid: diethylene glycol = 0.5 mole: 1.0 mole) The production method is shown in Example 1.

In a reactor equipped with a stirrer, a thermometer, and a gas introduction tube, 349 g (0.6 mol) of dimerized linoleic acid (PRIPOL1025 manufactured by UNIQEMA Co., Ltd.) and 127 g (1.2 mol) of diethylene glycol were fed in a nitrogen atmosphere. The mixture is heated to 210-220 ° C, and the esterification reaction is carried out for 12 hours while evaporating the generated water, and finally a dimerized linoleic acid diethylene glycol ester oligomer (dimerized sub-Asia) is obtained. Oleic acid: diethylene glycol = 0.5: 1.0) (hereinafter referred to as "DEG-DA5") 416g.

The physical property values of the obtained three kinds of oil agents are shown in Table 1 below.

(Example 2)

A dimerized linoleic acid diethylene glycol oligomer (dimerized linoleic acid: diethylene glycol = 0.8 mol: 1.0 mol) was used in Example 2 to show a production method thereof.

In a reactor equipped with a stirrer, a thermometer, and a gas introduction tube, 372 g (0.64 mol) of dimerized linoleic acid (PRIPOL1025 manufactured by UNIQEMA Co., Ltd.) and 84.8 g (0.8 mol) of diethylene glycol were charged. The mixture was heated to 210-220 ° C under a nitrogen stream, and the esterification reaction was carried out for 14 hours while evaporating the generated water, and finally a dimerized linoleic acid diethylene glycol ester oligomer was obtained in a pale yellow high-viscosity oil. Poly linoleic acid: diethylene glycol = 0.8: 1.0) (hereinafter also referred to as "DEG-DA8") 375 g.

The physical property values of the obtained oil agents are shown in Table 2 below.

<Drug skin penetration test>

The oil agent of Example 1 and a commercially available dimer acid ester and dimer diol ester were evaluated for their drug skin permeability.

1. Samples As shown in Table 3, in the oil agent (DEG-DA5) obtained in Example 1 and a commercially available dimer acid ester or dimer glycol ester, 1% ibuprofen was dissolved ( Sigma) samples were tested for drug skin penetration.

2. Experimental method The Yucatan Micropig back skin (5 months old, female, Japanese CHARLES RIVER) was stored frozen at -80 ° C and thawed at room temperature for 30 minutes to remove excess fat attached to the skin. Cut into squares of about 2 cm for experimentation.

The skin was sandwiched between cells at an effective area of 0.95 cm ^{2 and} 0.2 ml of the sample was applied. After 48 hours, by wiping off the sample on the skin surface, the skin was crushed with a forceps and a homogenizer in a methanol/0.1% phosphoric acid aqueous solution (70:30), and then ibuprofen was extracted (or It is ibuprofen), and the amount of ibuprofen in the skin is measured according to HPLC. The measurement results are shown in Table 3.

2.1 HPLC measurement condition detector: UV-absorbance photometer LC-10AD (manufactured by Shimadzu Corporation) Measurement wavelength: 220 nm chromatography tube: TSK-GEL ODS-80Ts 4.6 mm × 150 mm (East (share)) mobile phase : methanol: 0.1% phosphoric acid aqueous solution = 75:25 flow rate: 1 ml / min

2.2 Data processing CLASS-VP (Shimadzu Corporation (stock) system) was used to make different calibration lines according to the peak area of ibuprofen, and the concentration was determined after calculation.

3. Results The measurement results are shown in Table 3.

Ibuprofen is generally used as an indicator of transdermal absorbability. If the skin absorbs less ibuprofen, it means that it inhibits the absorption of stimulating substances.

When ibuprofen was dissolved in the oil agent (DEG-DA5) of Example 1, the amount of ibuprofen in the skin after 48 hours was 21 μg, and in this case, it was dissolved in a commercially available dimer acid. In the case of esters and dimerdiol esters, the amount of ibuprofen is from 37 μg to 70 μg. Even in the dimer acid ester or dimer diol ester, the oil agent (DEG-DA5) of Example 1 is excellent in suppressing the penetration of ibuprofen into the skin, and the absorption inhibiting effect of the stimulating substance is excellent. . Among the commercially available oils, although LUSPLAN DD-DHR: Japan's refined refining diethylene sulfoxide hydrogenated rosin copolymer (Ibuprofen 37 μg), LUSPLAN DD-DA7: Japan Refined (shares) The absorption of ibuprofen by dimerized linoleic acid dimerized linoleic alcohol (42 μg of ibuprofen) is also lower, but the viscosity of both oils is higher. It has a strong sticky feeling and a glare, so it is difficult to use it as a moisturizing cosmetic.

<Experiment of stimulation mitigation using collagen gel method>

The oil agent (DEG-DA5) prepared in Example 1 and the oil agent (DEG-DA8) prepared in Example 2 were compared with a commercially available oil agent to compare the stimulating effects.

1. Test substance The oil agent shown in Table 4 is added to the oil as it is, or lauric acid which is reported to be irritating to animal or human skin, is added to the oil at 0.5% by mass, 0.8% by mass, and 1.2% by mass. As a test substance.

2. Experimental method 2.1 Preparation of collagen gel A suspension of Type I-AC collagen (Gaoyan) aqueous solution and normal human fibroblasts (manufactured by CAMBLEX), and an appropriate amount of reconstituted solution were mixed with a stirrer. The final concentration of Type I-AC collagen (Gaoyan) was 0.1% by mass, and the final concentration of normal human fibroblasts (manufactured by CAMBLEX) was 4.0×10 ⁵ cells/mL in a 6-well culture dish (6 Well culture insert, made by FALCON) drops 1 mL. The culture medium uses DMEM + 10% FBS. The collagen is cultured for about 16 (12 hours to 24 hours) hours.

2.2 Applicability to collagen gel of test substance 0.5% by mass, 0.8% by mass, 1.2% by mass of lauric acid, and 1 g of no-addition test substance were added to the collagen gel prepared in 2.1, and exposed 24 Hours. After 24 hours of exposure, the test substance was removed, and the cell survival rate was measured by MTTassay, and the lauric acid concentration dependence of the cell survival rate was investigated.

3. The results are shown in Table 4.

Dimerized linoleic acid diethylene glycol ester oligomer (dimerized linoleic acid: diethylene glycol = 0.5: 1.0), even after the addition of 1.2% by mass of lauric acid, the cell survival rate is still about 80%. This shows that the stimulation and relaxation effect is excellent. Compared with those who did not add lauric acid, the cell viability of those who added 0.5% lauric acid increased although the data (DEG-DA5) prepared in Example 1 was 95%→104%, and LUSPLAN DD-IS was 72%→78%), but this is due to the clutter of data.

<Using cells for stimulation mitigation experiment>

A cream containing sodium lauryl sulfate was applied to normal human fibroblasts to investigate the stimulating effect of the cream on sodium lauryl sulfate.

1. The cream to be tested was a cream prescribed in Table 5, that is, the cream of Example 3, Comparative Example 1, and Comparative Example 2, and 10% of sodium lauryl sulfate was added to each cream and its cream. The aqueous solution was mixed, and the content of sodium lauryl sulfate in the cream was adjusted to 0.1%, and then used.

2. Experimental method The tested cream was mixed and diluted in the medium.

Normal human fibroblasts were seeded in a 96-well flat plate with a seeding area of 3.5×10 ³ and cultured for 5 days.

In the state in which the monolayer cells are dense, the concentration of the test cream is 0.156% to 20%, and the cells are mixed and diluted, and the cells are exposed to the test cream.

After 20 hours of exposure, cell viability was determined using MTT assay.

3. Results The cream containing sodium lauryl sulfate was observed as shown in Figure 1 when exposed to cells at various concentrations; a cream containing 0.1% sodium lauryl sulfate was exposed to cells at various concentrations. The survival rate at that time is shown in Fig. 2.

As shown in Fig. 1, all the examples are: a cream containing sodium lauryl sulfate, when exposed to cells at various concentrations, as the concentration of the cream in the medium increases from 0.156% to 20%, the survival rate It is roughly the same from 80% to 60%.

In addition, as shown in Fig. 2, when the cream containing 0.1% sodium lauryl sulfate was exposed to cells at various concentrations, even if the cream concentration in the medium was increased from 0.156% to 10%, all cases were all Yes, cell viability has decreased from approximately 80% to 70%.

However, when the cream concentration in the medium was adjusted to 20%, the cream containing 0.1% sodium lauryl sulfate in Example 3, although maintaining a cell survival rate of 54%, contained 0.1 in Comparative Examples 1 and 2. The % concentration of sodium lauryl sulfate cream, in which almost all of the cells showed a state of death (cell survival rate of 1%).

Therefore, the cream of Example 3 is particularly excellent in stimulating the stimulation of sodium lauryl sulfate.

<Stimulus mitigation experiment using skin test>

For the oil agent of Example 1, the cream of the oil of Example 1 (as Example 3), the fluid paraffin, and the mixed flow paraffin cream (Comparative Example 1), the sodium lauryl sulfate stimulation was evaluated by the skin test. The easing effect.

1. Pretreatment of the test article The oil agent of Example 1, the mobile paraffin, and the cream of Example 3 and Comparative Example 1 composed of Table 5 were applied to the skin before being used for the test of the skin test. .

2. Skin test The test article was treated with 0.5% aqueous sodium lauryl sulfate and sterilized water (control) as a skin test.

3. The subject used the previous skin test, the sodium-sodium lauryl sulfate 0.1~0.5% aqueous solution showed a pseudo-positive reaction, and the patch site did not have itching, rash and other skin symptoms, healthy 20-50 years old 12 people at the level (3 males and 9 females)

4. Experimental method The test article was treated before coating, and then a 24-hour close-attachment test using the skin test article as a sample was performed. Three places and two places (5 pieces in both hands) were marked in the hand on the inner side of the subject's upper arm in a range of 10 mm × 30 mm, and the percutaneous moisture evapotranspiration of each place was measured using a vapometer manufactured by Delfin. Next, the four pretreatment samples were coated with 10 μL each at a distance of 5 to 10 minutes (there was no coating of any pretreated sample). After confirming that the test article has penetrated into the skin, about 20 μL of the skin test article is dropped on the filter paper attached to the human body patch Finn chamber (diameter 11 mm, Taisho Pharmaceutical Co., Ltd.) and attached directly to the skin. At the subject's 5 markings for 22 hours. The patch was peeled off, and after 2 hours (after 24 hours of attachment) and 24 hours after the next day (after 48 hours of attachment), the skin reaction was visually observed according to the criteria shown in Table 6. The transepidermal water evapotranspiration was also measured.

5. Visual judgment results The visual judgment results are shown in Table 7.

In the case where the test article was not coated before application, the skin irritation evaluation value after attaching a 0.5% sodium lauryl sulfate aqueous solution for 24 hours was 0.750, and the average value of the skin irritation evaluation was lowered according to the condition of the test article before the application. In particular, the oil absorbing agent (0.208) of Example 1 and the cream (0.167) of Example 3 have a very significant stimulating effect, and the average value of the skin stimuli is reduced to 2 as compared with the case where the test article is not coated. /10~3/10. The cream of Comparative Example 2 (0.458) was 6/10 as compared with the case where the test article was not coated before the application, and there was a stimulating effect, but the fluid paraffin (0.667) was compared with the case where the sample was not coated before the test. At 9/10, there is almost no irritating effect.

In the case where the test article was not coated before application, the skin irritation evaluation value after attaching a 0.5% sodium lauryl sulfate aqueous solution for 48 hours was 1.083. Regarding the coating effect of the pretreated sample, the oil agent (0.333) of Example 1 was 3/10 as compared with the case where the test article was not coated before the coating, and therefore it was found that the oily agent had a remarkable stimulating effect. The cream (0.583) of Example 3 was 5/10 in comparison with the case where the test article was not coated before application, and it had a stimulating effect. The cream (0.792) of Comparative Example 1 was 7/10 as compared with the case where the test article was not coated before application, and although it was weak, it still had a stimulating effect. On the other hand, the average value of the skin irritation evaluation when the paraffin was applied was 1.292, which was 12/10 as compared with the case where the test article was not coated, and the stimulation of sodium lauryl sulfate was gradually enhanced.

Therefore, it was confirmed that the oil agent of Example 1 and the cream of Example 3 in which the oil agent of Example 1 were mixed had a remarkable stimulating effect.

6. Transdermal water evapotranspiration measurement results The results of percutaneous water evapotranspiration measurement are shown in Table 7.

In the case where the test article was not treated before coating, the transdermal moisture evapotranspiration amount after attaching 0.5% sodium lauryl sulfate aqueous solution for 24 hours was 8, and the transdermal moisture evapotranspiration amount when attaching sterile water was 3, compared with Underneath it is obvious that the skin is broken and the skin is rougher. By applying the oil agent of Example 1 and the cream of Example 3 in advance, the transdermal moisture evapotranspiration after attaching 0.5% aqueous sodium lauryl sulfate solution for 24 hours was 5 and 4, respectively, and there was no pretreatment of the test article. 8, can inhibit about half of the water evapotranspiration.

Therefore, it is possible to exert a stimulating effect and a skin roughness preventing effect. When the cream of Comparative Example 1 was applied in advance, the amount of transdermal water evapotranspiration after attaching a 0.5% aqueous solution of sodium lauryl sulfate for 24 hours was 7, and the amount of the test article without pre-coating treatment was hardly changed, so It has a stimulating effect and a skin roughness prevention effect. When the paraffin wax was applied in advance, the transdermal moisture evapotranspiration after the application of the 0.5% sodium lauryl sulfate aqueous solution for 24 hours was 11, which was about 1.4 times that of the pretreated sample 8, and the skin irritation and skin roughness were More enhanced.

In the case where the test article was not treated before coating, the transdermal moisture evapotranspiration after the application of the 0.5% sodium lauryl sulfate aqueous solution for 48 hours was increased to 12, and the skin roughness continued to be severe. By applying the oil agent of Example 1 and the cream of Example 3 in advance, the transdermal moisture evapotranspiration after the application of the 0.5% sodium lauryl sulfate aqueous solution for 48 hours was 4, which was the pretreatment of the test article 12 without coating. 1/3. Moreover, the difference between the transepidermal water evapotranspiration amount 2 after 48 hours from the application of the test article without the pre-coating treatment and the attachment of the sterile water was small. Therefore, the roughness of the skin is not deteriorated, and it is obviously mild, which can effectively inhibit the roughness of the skin. When the cream of Comparative Example 1 was applied in advance, the transdermal moisture evapotranspiration amount after attaching a 0.5% sodium lauryl sulfate aqueous solution for 48 hours was 8, which was 2/3 of the test article 12 before the coating treatment. Although it has a skin roughness preventing effect, it is not as noticeable as the oil agent of Example 1 and the cream of Example 3. When the paraffin wax was applied in advance, the transdermal moisture evapotranspiration after the application of the 0.5% sodium lauryl sulfate aqueous solution for 48 hours was 15 times, which was about 1.3 times that of the pretreatment coated article 12, skin irritation and skin roughness. More enhanced.

Therefore, it was confirmed that the oil agent of Example 1 and the cream of Example 3 in which the oil agent of Example 1 were mixed had a remarkable stimulating effect and a skin roughness preventing effect.

<For 20 men with atopic dermatitis or sebum deficiency, the skin test was used to stimulate the mitigating effect experiment>

The oil agent (DEG-DA5) of Example 1 and the cream of DEG-DA5 mixed with the human skin test were used to verify the stimulating effect of the test for subjects suffering from atopic dermatitis or sebum deficiency.

1. Subject 1-1 age consists of 20 males between the ages of 19 and 45, with an average age of 27.9 years, and no one withdraws during the experiment.

1-2 The skin disease of the subject Beforehand, the doctor in charge of the experiment should diagnose the symptoms of the subject. There were 11 subjects with atopic dermatitis and 9 with sebum deficiency. Among the subjects with atopic dermatitis, 7 had mild symptoms, 2 with mild to moderate, and 2 with moderate symptoms.

2. Pretreatment of the test article The oil agent of Example 1, the three types of cream mixed with the oil agent of Example 1, and the comparative example are generally used as a cosmetic oil agent mixed with flowing paraffin and squalene. A total of 4 kinds of creams, as well as Vaseline, which is often used as a moisturizer in dermatology, as a pre-treatment test, and no treatment as a control group.

(1) Cream of Example 3 mixed with 20% DEG-DA5 (2) Cream of Example 4 mixed with 10% DEG-DA5 (3) Milk of Example 5 mixed with 5% DEG-DA5 Cream (4) Cream of Comparative Example 1 mixed with 20% of flowing paraffin (5) Cream of Comparative Example 3 mixed with 10% of flowing paraffin (6) Cream of Comparative Example 2 mixed with 20% of squalene ( 7) Cream of Comparative Example 4 mixed with 10% squalene (8) Oil agent of Example 1 (DEG-DA5) (9) Glycerin (manufactured by Nikko Chemical Co., Ltd.) (10) No treatment (control)

The cream formulations of Example 3 and Comparative Examples 1 and 2 are shown in Table 5; the cream formulations of Examples 4 and 5 and Comparative Examples 3 and 4 are shown in Table 8.

Pretreatment agent safety experiment

In order to carry out the safety confirmation test of the pretreatment agent, it is necessary to carry out a 24-hour close-fitting test. 4 kinds of test substances attached [cream mixed with 20% DEG-DA5 (Example 3), cream mixed with 20% mobile paraffin (Comparative Example 1), cream mixed with 20% squalene ( The visual evaluation results of Comparative Example 2) and Vaseline are shown in Table 12. The cream mixed with DEG-DA5 and the cream mixed with paraffin wax were all negative at each determination time. Compared with the cream containing squalene, one subject showed a point at 24h. The number 3, mixed with Vaseline, was judged by a subject at 24h. However, the stimulatory response was reduced after 48 h and the 7th day, and no allergy symptoms were confirmed. From the above results, it was confirmed that the four test substances were occluded and attached for 24 hours, and it was apparent that the skin was not irritated once.

3. Skin test The test article was used to evaluate the skin irritation mitigation effect, and a 0.5% sodium lauryl sulfate (Kanto Chemical) aqueous solution (hereinafter referred to as SLS) of the skin irritant was used as a skin test test. Sterile water was simultaneously attached to each of the coated sites as a control.

4. The modified adhesion test method was applied to the back of the subject using a plastic frame at an area of 10 mm × 30 mm, and the oil agent (DEG-DA5) of Example 1 and glycerin and Examples 3 to 5 were used. In the creams of Comparative Examples 1 to 4, a fixed amount (about 15 μL) was taken by a micro-dispenser, and one pre-treated test article was applied at one place, and a total of nine coated areas of the pre-treated test article were applied. The remaining one was the untreated area as a control group.

Thereafter, 0.5% sodium lauryl sulfate (SLS) of the skin irritant and sterile water of the control group were used as a skin test, and a 24-hour close-fitting test was performed. The Skinn test's Finn chamber patch was used in the skin test.

The coating site can be selected from the left and right sides of the back bone, and the doctor in charge of the experiment inspects the back of the subject, avoiding the inflamed site such as erythema, and pre-treating the coated article and attaching the medicated cloth.

5. Evaluation items and evaluation time The following two items are evaluated.

1) Skin findings: visual determination of skin changes caused by skin testing (days 2, 3, 7) 2) Physical examination: measurement of transepidermal water evapotranspiration using a vapometer (Delfin) (experiment) Day 2, Day 3)

6. Evaluation method 6.1 The visual judgment of the skin is based on the skin irritation determination standard (Table 9), and is performed by the doctor in charge of the experiment. The judgment result is averaged by the evaluation point, and the obtained value is compared with the non-coating part and the Vaseline coating part, and the validity is judged.

6.2 Physical examination The measured value of transepidermal water evapotranspiration obtained by vapometer is analyzed by the difference between the attached and non-attached parts of each patch, and the values of the coated parts of each test substance are compared with The coating unit and the Vaseline coating unit were compared to determine the effectiveness.

7. Visually judged by the dermatologist 24 hours after, 48 hours, and 7 days after the attachment, the visual judgment was judged by the responsible physician based on the skin irritation standard, and the visual judgment results after 24 hours of attachment were as shown in Table 10. The results of the visual judgment after 48 hours of attachment are shown in Table 11. Fig. 3 and Fig. 4 show that in the skin irritation of 0.5% sodium lauryl sulfate aqueous solution (SLS) of 20 subjects of each pretreatment agent, only the skin irritation reference points were 3, 4, after passing through The total number of people after 24 hours and 48 hours. Among them, no subject's skin irritation reference points exceeded 4.

In the determination after 24 hours, the application site of the DEG-DA5 coated site (Example 1) and the cream containing 20% DEG-DA5 (Example 3) was visually evaluated as compared with the uncoated portion. Subjects with a number of 3 or more were significantly fewer, followed by a cream mixed with 10% DEG-DA5 (Example 4) and a cream mixed with 5% DEG-DA5 (Example 5). The number of visual evaluation points of Vaseline after being attached to 0.5% sodium lauryl sulfate aqueous solution (SLS) was 5 or more, and the number of subjects was 5, compared with 12 people without coating, the results were small. However, compared with DEG-DA5 and the cream mixed with DEG-DA5, the number is still too large. When the number of points in which the DEG-DA5 is mixed is equal to or greater than the number of points, it is possible to determine that the entire stimulus can be alleviated, and it is also possible to conclude that the number of people who have a strong stimulus and the number of points or more is less than the above. .

The DEG-DA5 coated site (Example 1), the cream mixed with 20% DEG-DA5 (Example 3), the application site, and the cream mixed with 10% DEG-DA5 according to the results of the Wilcoxon symbol summation test (implementation) Example 4) The application site was lower in comparison with the Vaseline coated site (p < 0.05). The cream mixed with 5% DEG-DA5 (Example 5) showed no significant inhibition tendency. Further, a cream containing 20% DEG-DA5 (Example 3) was compared with a cream containing 20% of flowing paraffin (Comparative Example 1) and a cream containing 20% of squalene (Comparative Example 2). Underneath, it is obviously more effective to suppress the number of stimulation points. In addition, a cream mixed with 10% DEG-DA5 (Example 4) was compared with a cream mixed with 10% of paraffin wax (Comparative Example 3) and a cream mixed with 10% squalene (Comparative Example 4). Underneath, it is also significantly more able to suppress the number of stimulation points.

In the judgment after 48 hours, the application site of the DEG-DA5 coated site and the cream containing 5% DEG-DA5 (Example 5) was compared with the uncoated portion, and the number of visual evaluation points was 3 or more. The subjects were clearly a minority, followed by a cream mixed with 20% DEG-DA5 (Example 3) and a cream mixed with 20% mobile paraffin (Comparative Example 1). Vaseline's visual evaluation points after SLS attachment showed 8 persons with 3 or more subjects, compared with 15 people without coating parts. Although the results were small, they were mixed with DEG-DA5 and DEG. -DA5's cream is still relatively large.

The DEG-DA5 coated site (Example 1), the cream mixed with 20% DEG-DA5 (Example 3), the application site, and the cream mixed with 5% DEG-DA5 according to the results of the Wilcoxon symbol-based summation test (implementation) Example 5) The application site was lower in comparison with the Vaseline coated site (p < 0.05). In addition, the cream mixed with 20% DEG-DA5 (Example 3) was significantly more resistant to stimulation than the cream mixed with 20% squalene (Comparative Example 2) (p<0.05). .

The judgment on the 7th day was carried out in order to confirm the presence or absence of allergy symptoms. As a result, there was only one subject having one or more points, and the SLS attachment site was not applied, and the pretreatment agent had no effect.

8. Measuring the transepidermal water evapotranspiration scale 13 by means of a machine, and Fig. 5 and Fig. 6 show the average value of the transepidermal water evapotranspiration amount of each test substance. After the attachment for 24 hours, it was confirmed that the part having the TEWL value inhibition tendency for the irritant was DEG-DA5 (Example 1) and the cream containing 20% DEG-DA5 (Example 3) at the SLS attachment site. A cream mixed with 10% DEG-DA5 (Example 4). The cream mixed with 20% DEG-DA5 (Example 3) and the cream mixed with 10% DEG-DA5 (Example 4) were used for the uncoated part or the cream mixed with 20% DEG-DA5 ( Example 3) It was confirmed that the Vaseline coated site had a stimulation inhibitory effect (p<0.05). After 48 hours of attachment, the TEWL value caused by SLS attachment was effectively suppressed (p<0.05) in all pretreatment agents compared with the uncoated portion. In particular, DEG-DA5 (Example 1), a cream mixed with 20% DEG-DA5 (Example 3) was more effectively inhibited (p < 0.05) than the Vaseline coated site.

13. Summary In this experiment, the osmotic inhibitory effect of the stimulating component of the DEG-DA5 and the DEG-DA5-containing cream was verified by using 20 patients with atopic dermatitis and sebum deficiency. As a result, it was found that DEG-DA5 and a cream containing DEG-DA5 have a tendency to suppress SLS stimulation depending on the concentration, and show the concentration at which the effect can be exerted when used in humans.

Moreover, according to the 24-hour close-fitting test, the safety of DEG-DA5 and DEG-DA5-containing cream for patients with atopic dermatitis and sebum deficiency can be confirmed.

From the above results, it is possible to know that the cosmetic material mixed with DEG-DA5 is very suitable for use in patients with atopic dermatitis and sebum deficiency in which the isolation function is low.

Figure 1 shows the survival rate of a cream containing no sodium lauryl sulfate when exposed to cells at various concentrations.

Figure 2 is a graph showing the survival rate of a cream containing 0.1% sodium lauryl sulfate exposed to cells at various concentrations.

Figure 3 is the sum of the subjects whose scores are indicated at 3, 4 after a 24-hour determination.

Figure 4 is the sum of subjects with scores of 3, 4 after 48 hours of judgment.

Fig. 5 is the average value of the transepidermal water evapotranspiration after 24 hours of attachment (mean ± S. D.).

Figure 6 is the average value of the transepidermal water evapotranspiration after 48 h of attachment (mean ± S. D.).

Claims (7)

A cosmetic containing diethylene linoleic acid diethylene glycol oligomer. The cosmetic material according to claim 1, wherein the ratio of the dimerized linoleic acid and the diethylene glycol is dimerized in the dimerized linoleic acid diethylene glycol oligomer. Oleic acid: diethylene glycol = 0.5 mole: 1.0 mole to 0.8 mole: 1.0 mole. The cosmetic material according to claim 1, wherein the ratio of the dimerized linoleic acid and the diethylene glycol is dimerized in the dimerized linoleic acid diethylene glycol oligomer. Oleic acid: diethylene glycol = 0.5 mole: 1.0 mole. The cosmetic according to any one of claims 1 to 3, wherein the dimerized linoleic acid diethylene glycol ester oligomer is a skin irritation absorbing component. The cosmetic according to any one of claims 1 to 3, which is characterized in that it is a moisturizing cosmetic for the face or the body. The cosmetic according to claim 2 or 3, which is characterized in that it contains 5 to 20% by mass of a dimerized linoleic acid diethylene glycol ester oligomer. An oil composition for a cosmetic containing diethylene linoleate diethylene glycol oligomer, which comprises a ratio of dimerized linoleic acid and diethylene glycol, dimerized linoleic acid: diethylene glycol = 0.5 mole: 1.0 mole to 0.8 mole: 1.0 mole.