TW200815042A - Cosmetic preparation containing dimer dilinoleic acid diethylene glycol oligomer ester - Google Patents

Abstract

Disclosed is a cosmetic preparation having excellent irritation reducing effects, which contains a dimer dilinoleic acid diethylene glycol oligomer ester.

Description

200815042 IX. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD The present invention relates to a cosmetic containing dimer dilinoleate diethylene giycol olig〇mer eSter. [Prior Art] In recent years, with the environment (4), patients with allergic diseases such as dermatitis, or people with skin allergies gradually increase, because these people's skin is easily allergic 'often caused by cosmetics and other items The redness, itching and other symptoms, and the demand for less stimulating makeup &, the market needs to provide a new, excellent ingredients to alleviate these stimuli.

It has been disclosed that a fatty acid ester of a staghorn sugar monomer (Patent Document 1: JP-A No. Hei. No. 45560), a pin ester having a perfluoroalkyl group and a polyoxyalkylene (10) fluorene is disclosed (Patent Document 2) (Japanese Unexamined Patent Publication No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No -Café) 'As an ethanol-stimulated tempering agent; & Fiber W Supplementary Literature 4: Tetra-flattenedic acid tri-filament, recorded (10) Mi _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Although the 'Inscription of Silk Recordings' in the fortune has been studied in silk. (Materials 1: Sugiyama, Ota, "Cosmetics, her money series, Japan «Skin Health Association, 1999 2^, Japanese skin = ― 142), but there has not been a tempering effect to enter the second 41 volumes, p about the right-to-take _ using 笊 仃 research. Face ^ cosmetics 'has been in the offer 6 (special open shaft tender shirt, Tactile, opposite

: In Li I, the persistence of the touch, and the ease of finishing the hair. A: There is no ambiguity to discuss _6+ ’. [Patent Document 1] Japanese Laid-Open Patent Publication No. Hei No. Hei. No. Hei. No. Hei. No. Hei. [Patent Document 5] JP-A-H05-255118 (Patent Document 6)

[Non-Patent Document 1] Sugiyama and Ota, "Skin Irritability Evaluation of Cosmetic Oily Raw Materials", Sakamoto Skin Association Series, Sakamoto Industrial Skin Hygiene Association, February 1999, Vol. 41, ρ·136-142 [Invention Contents 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: 200815042 (1) A cosmetic containing a poly(ethylene phthalate) oligomer. (2) In the cosmetic material of (1), the ratio of dimerized linoleic acid and diethylene glycol in the dimerized linoleic acid diethylene glycol oligomer is dimerized linoleic acid·· Diethylene glycol - 0 · 5 Mo · 1 · 〇 Mo Er ~ 〇 · 8 Mo Er: 1 · 〇 Mo Er. (3) In the cosmetic material of (1), the ratio of dimerized linoleic acid and diethylene glycol in the dimerized linoleic acid diethylene glycol oligomer is dimerized linoleic acid: diethylene Alcohol = 0.5 mole: 1.0 mole. (4) The cosmetic material of (1) has a dimerized linoleic acid diethylene glycol oligomer having a viscosity of 2,500 to 4,500 mPa·s in a °C. (5) The cosmetic material of any one of (1) to (4), wherein the dimerized linoleic acid diethylene glycol ester oligomer is a skin irritation mitigating component. 6 (6) A cosmetic according to any one of (1) to (5), which is a facial or body moisturizing cosmetic. Protection

(7) The cosmetic according to any one of (2) to (6) which contains 5 to 2% by mass of a poly-linoleic acid diethylene glycol ester oligomer. (1) - a cosmetic agent containing diethylene linoleate diethylene glycol oligomer, which comprises a ratio of dimerized linoleic acid to diethylene glycol, dimerized, / / By Ethylene Glycol = Q · 5 Mo · U Mo ~ G_ 8 Mo · 1 · G Mo. ^ - - According to the present invention, the following effects can be achieved.乂 and 3 have the oil agent. 1. It can provide a cosmetic which is excellent in stimulating the emollient effect. 7 200815042 2. Since the cosmetic absorbing effect of the present invention is superior, it is possible to suppress the isolation and wrap caused by the skin of the agonist (4) by using the cosmetic of the present invention, and to improve the skin by inhibiting the isolation and destruction. It is rough and protects the skin, so it can provide a cosmetic that has excellent skin roughness and excellent health effects. 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 dryness accompanying skin irritation, thereby preventing aging. 4. Since the dimer linoleic acid diethylene glycol oligomer used in the cosmetic of the present invention is not sticky, sticky, and glare-sensitive, it is suitable for use in lotions, creams, and the like. Use a cosmetic. [Embodiment] 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 dimeric linoleic acid with diethylene glycol. <Dimerized linoleic acid> Dimerized linoleic acid is a dibasic acid generally called a dimer acid, and two molecules of linoleic acid [(9Z, 12Z)-octadec-9 a 2-mer of linoleic acid after polymerization of an unsaturated fatty acid such as 12-dienoic acid. Among the products of the linoleic acid polymerization, in addition to the 2-mer of linoleic acid, unreacted linoleic acid and a trimer 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 the method of molecular vaporization 200815042. 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 deuterated 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. For the deuterated dimer acid, a commercially available product such as PRIP〇L1〇〇6, PRIP〇L1〇〇9, PRIPOL1025, etc. produced by UNIQEMA Corporation can be used. <Diethylene glycol> Diethylene glycol is a compound represented by the chemical formula of hydrazine (CH2CH2〇H) 2 and is marketed as a raw material for organic synthesis. The dimerized linoleic acid is polymerized with diethylene glycol to carry out an esterification reaction, and the copolymerization is carried out by the copolymerization of the dimeric yakisaki. There is no specific regulation for the method of self-determination, for example, no catalyst or use of p-benzoic acid, sulfuric acid, hydrochloric acid, methyl scutellaria, etc. as a catalyst, no solvent or use of toluene, hexapril (five), heptane ( H intane), etc. as (5) media, edited in 5Q~. The reaction can be carried out at a temperature of c. The ratio of dimerized linoleic acid to diethylene glycol of linoleic acid and diethylene glycol is 〇····················································· When dimerization / 酉夂 酉夂 乙 乙 乙 莫 莫 莫 : : : : : I I I I I I I I I I I I I I I I I I I 丝 丝 丝 丝 丝 丝 丝 丝 丝 丝 丝 丝 丝The substance is distributed as a center. When -water sub-grain--ethylene glycol is 〇8 mol: L 〇 Mo ear, an oligomer will be formed, 200815042 which is an ester combination of 4 dimerized linoleic acid and 5 diethylene glycol The latter matter is distributed as a center. In either case, t diethylene glycol is more abundant than dimerized linoleic acid. Therefore, 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 that, the degree of aggregation will be large, and the viscosity of the oil agent will increase, so it is not ideal. Further, if the dimerized linoleic acid has a large amount of molybdenum diethylene glycol, the residual functional group will become a carboxyl group, which is not preferable from the viewpoint of safety. In particular, the ratio of the dimerized linoleic acid and the diethylene glycol is composed of dimerized linoleic acid ethyl ketone · 5 mol. j. 〇 Moel, at 25. The viscosity in sputum is & just ~ 4' 50 〇 mPa · s dimerized linoleic acid diethylene glycol vinegar oligomer, it can be found that the drug has small skin permeability, and it is __, wealth It is used for evapotranspiration, so it can be determined that it has a high effect of preventing skin thickening. For this effect, there is a significant difference even when compared with a similar type of acetylene ester oligomer. However, in Patent Document 6, although it is suitable for blending various dimerized linoleic acid The cosmetic of ethylene glycol vinegar oligomers was reviewed, but no stimulating effect was discussed. In Patent Document 6, although dimerized linoleic acid diethylene glycol vinegar oligomer (dimer acid: ^ethylene glycol = 1: 〇·5) / mixed ethanol (twenty-two scale: different ten Octaol: Plant alcohol 9. 1 · 1) Cool, but the proportion of the present invention, that is, dimerized linoleic acid. Diethylene glycol = 〇 · 5 moles: I 0 Moer ~ 〇. 8 Molar :1. 〇莫耳二聚200815042 Linoleic acid diethyl -2- oligopolymer, but there is no disclosure, the polarity is different, the physical properties and usability of the two are completely different. The recording material + the dimerized linoleic acid diethylene glycol telomer of the invention has no fixed amount, but is different from the total amount of the cosmetic material.

The amount % is more suitable. When the cosmetic is a moisturizing cosmetic, the amount of the dimerized linoleic acid diethylene glycol vinegar oligomer is suitably (U~4〇f%, and more preferably 5 to 2% by mass). If the blending amount is 4% by mass, it will not be suitable as a cosmetic because the stickiness is too strong; if it exceeds 2 ()% by mass or more, the sensation will become stronger; however, if the blending amount is 5% by mass or less The stimulating effect will be weakened, and when it is less than 1% by mass, there is almost no stimulating effect. The cosmetic materials (including quasi-drugs) include lotions, lotions, creams, Hand cream, body lotion, beauty lotion, sunscreen lotion, liquid foundation, lipstick, etc. Since the cosmetic of the present invention has a remarkable stimulating effect and a skin roughness preventing effect, it is very suitable for use as a moisturizing cosmetic. The lotion, the lotion, the cream, the hand cream, the body lotion, the melamine liquid, etc. may be mentioned. The cosmetic of the present invention may be used in accordance with the purpose, purpose of use, dosage form, etc. 5 oil like vegetable oil Lipid, southern fatty acid, southern ethanol, anionic surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant, preservative, sugar, metal ion blocker, powder component, UV absorber, UV-blocking agents, such as hyaluronic acid moisturizers, perfumes, pH adjusters, etc. 11 200815042 = It can also contain vitamins, skin side, blood-staining agent, beneficial bacteria (4) 4, hypoxia, remover, Other medicinal ingredients and physiologically active ingredients such as anti-inflammatory agents, whitening agents, and gluing agents. Examples of oils and fats include pile oil, valerian oil, Hawaiian stone fruit (Macadamia nut) U, olive oil, rapeseed oil, and corn. Oil, sesame oil, jojoba oil, germ oil, wheat germ oil, tricapry glycerol and other liquid fats, cocoa butter, raisin oil, hardened coconut oil, palm oil, palm kernel oil, wood bad nuclear oil, hardened oil, Solid oil such as hardened lotus oil, candied fruit, candied fruit, cotton sacrifice, smashed, lanolin, lanolin acetate, liquid lanolin, sugar cane, mobile stone ants, lin, grade oil, micro For higher fatty acids, lauHc acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linoleic acid (1 inolenic acid), and Docosahexaenoic acid (DHA), eic〇saperrtaen〇ic add (epa), etc. Regarding higher alcohol, lauryl alcohol, hard Linear alcohols such as aliphatic alcohol, cetyl alcohol, cetostearyl alcohol, monostearyl glycerin ether, lanolin alcohol, cholesterol (phytosterol), phytosterol, a branched chain alcohol such as octyl dodecanol. Examples of the anionic surfactant include fatty acid salts such as sodium laurate and higher alkyl sulfates such as sodium lauryl sulfate, and burnt ether sulfates such as poe 12 200815042 triethanolamine. , N - acylsarcosine, sulfosuccinate, N-decylamino acid salt, and the like. The cationic surfactant may, for example, be an alkyltrimethylammonium salt such as stearyl triammonium chloride, benzalkonium chloride or benzethonium chloride. The amphoteric surfactant may, for example, be a betaine-based surfactant such as an alkyl 10betaine 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, etc. • Regarding the metal ion blocking agent, disodium edetate (sodium diamine tetraacetate) Disodium ethylenediaminetetraacetate), _ acid, sodium salt and other salts. = inhibit the mechanical sense, and increase the color, _ powder composition, can be listed as talc, kaolin, mica, baby, zeolite, polyethylene powder, polystyrene Powder, cellulose powder, inorganic white pigment, inorganic red pigment, titanium dioxide coated mica, titanium oxide coated stone, pigmented titanium dioxide coated mica and other pearlescent pigments, red 13 200815042, red 202 and other coal char pigments (tar dye About UV absorption _ 'solvable (four) ammonia f acid), phenyl saiicylate, isopropyl p-meth〇xyCinnamate> p-methoxy cinnamic acid vinegar (〇ctyl p-methoxycinnamate), 2, 4-dihydroxydiphenyl@同C 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, s〇dium ch〇ndr〇丨tin sulfate, and sodium hyaluronate (sodium). Hyaluronate), sodium lactate, pyrr〇iid〇ne carboxylic acid, cyclodextrin, and the like. Examples of the medicinal ingredient include vitamin A such as vitamin A oil and retinol, vitamin B 2 such as riboflavin, b 6 such as pyridoxine hydrochloride, pantothenic acid such as calcium pantothenate, and vitamin D2. Vitamin D, such as ch〇lecaicifer〇i, tocopherol acetate, DL-α-tocopherol nicothinate, etc. Vitamins. Other examples include skin activators such as royal jelly and beech extract, capsaicin, zingerone, cantharides tincture, and fish<i> 14 200815042 stone fat, caffeine, monoacid , 7"-[7-〇ryZan〇i) and other blood circulation promoters, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, azulene and other anti-inflammatory agents, 'sperm ammonia Amino acids such as arginine, serine, leucine, and 廿Tptophan, maltose sucrose condensate of beneficial bacteria control agent, lysozyme chloride Wait. In addition, it can also be combined with such as 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 scent extract, algae extract Various extracts such as extracts, cucumber 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. 〇 Mo ear) is shown in Example 1 method. In a reactor equipped with a stirrer, a thermometer, and a gas introduction tube, a feed of 15 200815042 dimerized linoleic acid (prip〇u〇25 manufactured by UNIQEMA Co., Ltd.) 349g (〇·6 mol) and diacetyl alcohol 127g (1.2) Moer) 'heated to 21 〇 to 22 〇 in a nitrogen atmosphere, and evaporates the generated water for 12 hours. The final reaction yields a yellowish, viscous oily dimerization. _The target (dimerized linoleic acid: diethylene glycol = 〇·5: 1·〇) (hereinafter referred to as "deg_M5") 4 runs. The physical property values of the obtained three oil agents are shown in the following table. [Table 1] Type of viscosity (25 ° C) (mPa · s) Molecular weight 氺 1) Acid value tortuosity type 1 3320 1,470 1.0 1.4733 Type 2 3328 1,500 1.0 1.4733 Type 3 3175 1,500 1.0 1.4733 *1) Measured by GPC method Number average molecular weight (Example 2) Diethylene linoleate diethylene glycol oligomer (dimer linoleic acid: diethylene glycol = 〇·8 mol: 1·〇莫耳) as an example 2, indicating its manufacturing method. In a reactor equipped with a stirrer, a thermometer, and a gas introduction tube, a dimerized linoleic acid (PRIPOL1025 manufactured by UNIQEMA Co., Ltd.) 372 g (0.64 mol) and diethylene glycol 84·8 g (〇·8 mol) were charged. , after heating to 210~220 C ' ^~ under a nitrogen stream, the generated water is evaporated while performing a 14-hour S-reaction reaction, and then the dimerized linoleic acid is added to the light-paste oil. Ethylene glycol g oligo (> 聚聚亚16 200815042 夂 一 〇 8 8 · 〇 ( ( ( () (hereinafter also referred to as "Na - Ying") 375g. The physical property values of the obtained oil agents are shown in Table 2 below. [Table 2], no

Viscosity (25 ° C) (mPa · s) 40000 Category 1

Acid value tortuosity rate ";------ 1.7 -1.4753 i drug skin permeation ^1 The oil of Example 1 and commercially available dimer acid vinegar, dimer diol _, for its drug skin Permeability is evaluated. 1. Samples As shown in Table 3, in the oil agent (DEG-Μ5) obtained in Example 1 and a commercially available mono- or di-glycol ester, 1% ibuprofen was dissolved ( Sigma) samples were tested for drug skin penetration. 2. The method of continuous preservation is to store the cold linger on the back skin of -8 (TC of Yucatan Micropig (5 months old, female, CHARLES RIVER, Japan), and thaw at room temperature for 3 minutes, remove the skin. After excess fat, cut into squares of about 2 cm for experiment. The skin was sandwiched between cells at an effective area of 0.95 cm 2 and coated with 0.2 ml of the sample. After 48 hours, the sample on the skin surface was removed by wiping, in methanol / 0·1% aqueous acid solution mixture (70: 30), using the recording and homogenizer 17 < η > 200815042 (homogemzer) to break the skin and then extract ibuprofen (or isobutyl phenylacetate) (ibuprofen)), the amount of ibuprofen in the skin was measured by HPLC. The measurement results are shown in Table 3. 2.1 HPLC measurement condition detector: UV spectrophotometer LC-10AD ((share) Shimadzu Manufacturing Co., Ltd.) Measurement wavelength: 220nm Chromatography: TSK-GEL ODS-80Ts 4.6mmxl50mm (East (share)) Mobile phase: decyl alcohol: 0·1% squaric acid aqueous solution = 75 : 25 Flow rate: lml / min 2.2 data processing Use CLASS-VP (Shimadzu Corporation (stock) system), in accordance with ibuprofen The peak area is made into different calibration lines, and the concentration is calculated after calculation. 3. The results of the measurement are shown in Table 3. Ibuprofen is generally used as an indicator of transdermal absorption. The absorption of styrene-butanoic acid is small, which means that the effect of inhibiting the absorption of the stimulating substance is good. When ibuprofen is dissolved in the oil agent of Example 1 (DEG-DA5), the skin is different after 48 hours. The amount of styrene-butanoic acid was 21, and in this case, the amount of the commercially available dimer acid i曰, 'mono-alcohol S 曰 寸', and the amount of the isobutyric acid was 37//g/^^70/zg. Even in the dimer acid ester or dimer diol ester, the oil agent (DEG-DA5) of Example 1 has an excellent effect of inhibiting the penetration of the isobutyric acid into the skin, and the absorption of the stimulating substance is also inhibited. Very good. In the market oil agent, although LUSPLAN DD-DHR: Japan Elaboration (shares)

Dimerized linoleyl hydrogenated rosin copolymer (Ibuprofen amount 37#g), LUSpLAN DD-DA7: Diuretic linoleic acid dimerized linoleic alcohol (Ibuprofen) manufactured by Nippon Seika Co., Ltd. The amount of ibuprofen absorbed by 42//g) is also low, but the viscosity of both oils is partial, sticky and glare, so it is difficult to use for moisturizing cosmetics. . [Table 3] Table 3 The amount of ibuprofen in the skin after 48 hours of dissolving 1% ibuprofen (#g) The oil of Example 1 (DEG-DA5) 21 LUSPLAN DD- DHR 37 LUSPLAN DD-DA7 42 LUSPLAN PI-DA 53

LUSPLAN DD-IS 70 LUSPLAN DD-DHR: Japan's refined (5) tripoly linoleyl hydrogenated rosin copolymer LUSPLAOD-DA7: Japan's refined (share) dimerized linoleic acid dimerized linoleic alcohol LUSPLAN PI-DA:曰本精化(股)制制聚聚酸酸(synthetic vinegar/plant LUSPLAN DD一IS ··Japan Refined (Monthium stearate dimerization] using collagen gel method for symmetry experiment > will be implemented The oil agent (10) prepared in Example 1 and the oil agent (DEG-DA8) prepared in Example 2 were compared with commercially available oil agents to compare the effects of stimulation and relaxation. It is indicated that the silk is scented, or the lauric acid which is reported to be irritating to the animal or human skin, is 5 mass%, 〇8 denier 0 U shell!% 19 200815042 is added to the oil as a test substance. Experimental Method 2·1 Preparation of Collagen Gel A suspension of Type I-AC collagen (Gaoyan) aqueous solution and normal human fibroblasts (manufactured by CAMBEX), and an appropriate amount of reconstituted solution were mixed with a stirrer. Modulation, the final concentration of Type i-AC collagen (Gaoyan) is 〇. i mass%, normal human fibroblasts CAMBLEX Ltd.) to a final concentration of 4 〇x

10 cells/mL, 1 mL was dropped in a 6-well culture dish (6 weu cuiture insert, manufactured by FALC® N). The culture medium uses DMEM+1〇%FBS. Collagen is cultured for approximately 16 (12 hours to 24 hours) hours. 2.2 Applicability to the collagen gel of the test substance: 5% mass%, 〇8 mass%, 1.2 mass% of lauric acid were added to the collagen gel prepared in 2.1, and ig was added. Check the substance and expose % of the small defects. 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. Results The results are shown in Table 4. Dimerized linoleic acid diethylene glycol ester oligomer (dimerized linoleic acid · diethylene glycol = 〇. 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 its stimulating effect is excellent. Compared with the case of no lauric acid added, the cell viability of the person who added 0.5% lauric acid increased although the data was improved (Example 20 200815042 1 The oil agent (DEG-DA5) was 95%-104%, LUSPLAN DD -IS is 72% - 78%) 'But this is the result of data clutter. [Table 4] Cell viability test results (%) Table 4 Oil agent lauric acid added concentration (%) 0 0.5 0.8 1.2 The oil agent prepared in Example 1 (DEG-DA5) 95 104 91 77 The preparation of Example 2 Oil (DEG-DA8 ) 107 80 42 16 LUSPLAN DD-IS 72 78 23 6 LUSPLAN PI-DA 62 51 49 18 Soybean Oil 93 49 4 4 Macadamia Seed Oil 84 16 3 1 3 Sesame Oil 74 74 "37 9 Sunflower Oil 87 71 14 2 Flowing stone fiber 86 3 4 ---- 3 Olive squalene------^ 96 3 3 2 Isopropyl palmitate 68 29 ---— 2 — 2 octyl palmitate 73 56 1 - ---~:— 2 octanoic acid silk 38 14 2 2 neopentanoic acid synthetic ester 80 35 '——. 11 —---- 3 LUSPLAN PI-Μ : Japan's refined (share) system of distearic acid II Polyarylene alcohol dimerized linoleic acid (synthetic ester/phytol) <Using cells for stimulation 縘>

21 200815042 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 creams 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 〇·1%, and then used. _ [Table 5] Table 5 Example 3 Comparative Example 1 Comparative Example 2 Oil agent Oil agent of Example 1 (DEG-DA5) 20.0 Flowed paraffin 20.0 Squalene 20.0 Ingredients other than oil The behenol 3.0 3.0 3.0 Glycerol 30.0 30.0 30.0 1,3-butanediol 4.0 4.0 4.0 Maltitol 0.4 0.4 0.4 Astaxanthin 0.1 0.1 0.1 Carboxyvinyl polymer 0.5 0.5 0.5 Sanxian gum 0.1 0.1 0.1 Stearic acid monoglyceride 1.0 L0 1.0 Arginine 0.5 0.5 0· 5 Residual residue of water residue 22 200815042 2. Experimental method The tested cream is mixed and diluted in the medium. The normal human fibroblasts were sown in a 96-well plate with a seeding area of 3.5×1〇3 ′ for 5 days. The cells were exposed to the test cream in a state in which the monolayer cells were adhered to each other so that the concentration of the test cream became 0·156% 20%'. After 20 hours of exposure, cell viability was determined using MTT assay. _ 3. The result will be a cream containing sodium lauryl sulfate, the survival rate when exposed to cells at various concentrations is shown in Figure 1; a cream containing 〇·1% concentration of sodium lauryl sulfate at various concentrations The survival rate when exposed to cells is shown in Figure 2. As shown in Figure 1, the creams containing sodium lauryl sulfate are exposed to cells at various concentrations, and the concentration of the cream in the medium increases from 〇·156% to 20%. The survival rate was approximately reduced from 8〇% to 6〇%. In addition, as shown in Fig. 2, when the cream containing sodium sulphate concentration of sodium lauryl sulfate was exposed to cells at various concentrations, even if the concentration of the cream in the medium was increased from 〇156% to 10%, each case All of them, the cell survival rate was roughly reduced from 8〇% to 70%. However, when the cream concentration in the medium was adjusted to 2% by weight, the cream containing 〇·1% sodium lauryl sulfate in Example 3, although maintaining a cell survival rate of 54%, Comparative Examples 1 and 2 The cream containing 〇·1% concentration of sodium lauryl sulfate, in which the cells 23 200815042 almost all 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.

For the oil agent of Example 1, the cream of the oil of Example 丨 (as Example 3), the liquid sarcophagus, and the cream of mixed mixed sarcophagus (Comparative Example), the skin test was used to evaluate the lauryl Sodium sulphate stimulating effect. 1. Pretreatment of the test article The oil agent of Example 1, the flow stone butterfly, 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. on. 2. Skin test test The 〇· 5% sodium lauryl sulfate aqueous solution and sterile water (sterilized) (as known) are used as skin-care products. 3. The subject, ... used in the previous skin test, for the sodium laurate sulfate 〇 〇 〇 水 水 水 壬 壬 壬 壬 壬 壬 壬 壬 壬 壬 壬 , , , , , , , , , , , , , , , , , , , , , , , , , 2〇~5〇 years old person's name ^ (3 males and 9 females) 4·Experimental method Pre-treatment of the test article, followed by the skin test test for the sample 24 i read (4) read. Before the subject's upper arm is closed, (7) with the application of the X-handler's no more than 3 places and 2 places (both hands add up to 5 pieces), use (4) such as 24 200815042 system vapometer to measure the percutaneous water everywhere The amount of evapotranspiration. Next, the four kinds of pretreated samples were coated with 1 〇/zL at each position, and allowed to permeate for about 5 to 1 minute (the remaining portion was not coated with any pretreated article). After confirming that the test article has penetrated into the skin, 'drop about 20//L of the skin test article on the filter paper attached to the human body patch Finn chamber (diameter π face, Taisho Pharmaceutical), directly close Attached to 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 10 criteria shown in Table β. The transepidermal water evapotranspiration was also measured. [Table 6] Table 6 National benchmark response evaluation Skin irritation evaluation mean 2 general evaluation points and / number of subjects - no response 0 soil a little erythema 0.5 + obvious erythema 1 + + erythema + edema, papules 2 + + + erythema + edema , Qiu treatment + small blisters 3 + + + + large blisters 4 5. Visual judgment results The visual judgment results are shown in Table 7. In the absence of pre-treatment of the test article, the average value of skin irritation after 5% sodium lauryl sulfate solution for 24 hours is 〇. 75G, according to the pre-coating treatment 25 200815042, the skin irritation The average rating will decrease. In particular, the oil-suppressing agent (0.208) of Example ^ and the cream (〇167) of Example 3 have a very significant effect of stimulating the mitigation of the test article, and the average value of the skin (4) stimuli is reduced to 2/1G~3/1G. The cream α 458) of Comparative Example 2 has a stimulating effect of 6/1Q as compared with the case where the pretreated sample is not coated, but the flow stone butterfly (0.667) is different from the case where the pretreatment sample is not coated. The ratio is 9/1{), and 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 〇.5% of sodium lauryl sulfate aqueous solution for 48 hours was 1〇83. 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 sample was not coated before the coating, and therefore it was found to have a remarkable stimulating effect. The cream (〇·583) 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 of Comparative Example 1 (〇.792) was 7/1 相比 as compared with the case where the pretreated sample was not coated, and although it was weak, it still had a stimulating effect. On the other hand, the average value of skin irritation when applying paraffin wax was 1292, which was 12/10 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. 26 200815042 [Table 7] Table 7 National standard skin irritation evaluation average percutaneous water evapotranspiration g/(m2 · hr) Pretreatment sample Skin test The test article is attached for 24 hours and attached for 48 hours. After 24 hours, after attaching for 48 hours, attach 24 hours and attach 48 hours after the oil of Example 1 (DEG-DA5). Sterile water ± 1 +1 + 1 0.125 0. 042 2 1 0.5% lauryl Sodium sulphate aqueous solution ± 5 ± 6 +1 + 0.208 0. 333 5 4 Example 3 Cream sterile water ± 1 +1 0 0 0.125 0. 000 1 0.4 0. 5% sodium lauryl sulfate aqueous solution ± 4 Name ± 6 + 4 0.167 0. 583 4 4 Flowing paraffin sterile water ± 3 0 0 0.125 0.000 2 2 0.5% sodium lauryl sulfate solution ± 6 + 3 ± 1 + 11 0.667 1.292 11 15 Compare Example 2 Cream sterile water ± 3 0 0 0.15 0. 000 2 2 0 · 5% aqueous solution of sodium lauryl sulfate ± 5 + 2 ± 5 1 + 6 0.485 0. 792 7 8 No coated sterile water ± 2 + 2 + 2 0. 250 0.083 3 2 〇 · 5% aqueous solution of sodium lauryl sulfate ± 6 + 5 soil 2 + 9 0. 750 1.083 8 12 6 · Transdermal moisture evapotranspiration measurement results Skin water evaporation measurement results are shown in Table 7. 27 200815042 In the case where the test article is not treated before coating, the transdermal moisture evapotranspiration after attaching 〇·5% sodium lauryl sulfate aqueous solution for 24 hours is 8 and the transdermal moisture evapotranspiration when the sterile water is attached is 3, in contrast, it can be clearly seen that the skin isolation is destroyed 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 the 5% 5% sodium lauryl sulfate aqueous solution for 24 hours was 5 and 4, respectively. At the inspection of 8, it can suppress about half of the water evapotranspiration. Therefore, it is possible to exert a stimulating effect and a skin roughness preventing effect. In the case where the cream of Comparative Example 1 was applied in advance, the percutaneous moisture strip I of the 0.5% sodium lauryl sulfate aqueous solution was attached for 24 hours, and the peeling I of the test article was almost 7; It is full, so it does not have a stimulating effect and a skin thick chain preventing effect. When the paraffin wax was applied in advance, the transdermal moisture evapotranspiration after attaching the 0.5% sodium lauryl sulfate aqueous solution for 24 hours was 11 times, which was about L 4 times that of the pretreatment coated product δ, skin irritation and rough skin. The degree is even stronger. In the case where the test article was not treated before coating, the transdermal moisture evapotranspiration after the 〇·5% sodium lauryl sulfate aqueous solution was applied for 48 hours was increased to 12, and the skin roughness was 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 〇·5 % sodium lauryl sulfate aqueous solution was applied for 48 hours was 4, which was the pretreatment without the coating. 1/3 of 12. 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 obvious that it can effectively inhibit the roughness of the skin. 28 200815042 When the cream of Comparative Example 1 was applied in advance, the transdermal moisture evapotranspiration after the 〇·5% sodium lauryl sulfate aqueous solution was applied for 48 hours was 8, which was 2/ of the pretreatment sample 12 without coating. 3. Although it had a skin roughness preventing effect, it was 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 newly treated test article 12, skin irritation and skin. The roughness is more enhanced. Therefore, it was confirmed that the oil of Example 1 and the cream of Example 3 in which the oil of Example 1 were mixed all had significant irritation and relaxation effects and skin thick chain prevention effect.

Line stimulation mitigation effect experiment> Validation of the example using the human skin test! The oil agent (DEG-Μ5), a courtesy of DEG M5, has a stimulating and stimulating effect on a subject suffering from atopic dermatitis or sebum deficiency. 1. Subjects 1 - 1 age composition Males between the ages of 19 and 45 are 2, the average age is 27.9 years old, and no one withdraws during the experiment. 1 to 2 skin diseases of the subject Beforehand, please consult a doctor who is responsible for the diagnosis of the symptoms of the face. There were 11 subjects with different dermatitis 2008, and 9 with sebum deficiency. Among the subjects with atopic dermatitis, 7 had mild symptoms, mild to moderate with 2, 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 a flowing stone butterfly and a shark. A total of 4 kinds of enamel creams, and 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% shark (8) Oil of Example 1 (DEG-DA5) (9) Glycerin (manufactured by Daisei Chemical Co., Ltd.) (10) No treatment (control) Example 3 The cream prescription of the example 2 is shown in Table 5; the cream prescriptions of Examples 4 and 5 and Comparative Examples 3 and 4 are shown in Table 8. Full-scale experiment In order to carry out the pre-treatment _ safety reliance experiment, a 24-hour secret 200815042 skin test must be implemented. 4 kinds of test substances to be attached [cream mixed with 2% DEG-DA5 (Example 3), cream mixed with 20% mobile paraffin (Comparative Example 1), milk mixed with 2% squalene The visual evaluation results of the cream (Comparative Example 2) and Vaseline] are shown in Table μ. The cream mixed with deg-DA5 and the cream mixed with the mobile sarcophagus were all negative at each determination time. Compared with the squalene cream, there was one subject at 24h. The number of points presented is 3'. When Vaseline is mixed, one subject presents a point of 1 at the time of judgment at 24h. However, the stimulatory response was reduced after 48 h and the 7th day, and it was confirmed that there was no _ allergy symptom. From the above results, it was confirmed that the results of the attachment of the four test substances to the closed cells for 24 hours were not significantly irritating to the skin.

31 200815042 [Table 8] Table 8 Example 4 Example 5 Comparative Example 3 Comparative Example 4 Oil agent Oil agent of Example 1 (DEG-DA5) 10.0 5.0 Flowing paraffin 10.0 Squalene 10.0 In addition to the oil agent, behenyl alcohol 3.0 3.0 3.0 3.0 Glycerin 30.0 30· 0 30.0 30.0 1,3-Butanediol 4.0 4.0 4.0 4.0 Maltitol 0.4 0.4 0.4 0.4 Alizarin 0.1 0.1 0.1 0.1 Carboxyvinyl polymer 0.5 0.5 0.5 0.5 Sanxianjiao 0.1 0.1 0.1 0.1 Decaglyceryl monostearate 1.0 1.0 1.0 1.0 arginine 0.5 0.5 0.5 0.5 Residual residue of water residue 3. Skin test The test article is used to evaluate the irritating effect of skin irritation, 0.5% laurel of skin irritant A sodium sulfate (Kanto Chemical) aqueous solution (hereinafter referred to as SLS) is used as a skin test test. Sterile water was simultaneously attached to each of the coated sites as a control. 4·Modification and close-fitting test method The test method is to use a plastic frame on the back of the subject to set 10 areas of 10 mm×30 mm, and compare the oil agent (DEG-DA5) of Example 1 with glycerin and Examples 3 to 5. Example 1~ 32 3 200815042 4 cream 'fine micro-dispenser split to take a fixed amount (about π), 1 place to apply a type of reading test, pre-treatment of the test article has a total of 9 areas The remaining 1 is the untreated area as a control group. After that, the skin irritant substance, 5% sodium lauryl sulfate (SLS) and the sterile water of the group, were used as a skin test, and a 24-hour close-fitting test was carried out; It is the Finn patch of Taisho Pharmaceuticals. The β-coated part 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 area such as erythema, and pre-treating the coated article and attaching the medicated cloth. 5. Evaluation items and evaluation time The following two items were evaluated. οWhat the skin sees: visual judgment of skin changes caused by skin test (experimental day 2, day 3, day 7) 2) Physical examination: measurement of transepidermal water evapotranspiration using vaqingter〇)elfin) (Establishment Day 2, Day 3) 6. Evaluation Method 6.1 The visual judgment of the skin was based on the skin irritation criterion (Table 9), and was performed by the doctor in charge of the experiment. The judgment result was averaged by the evaluation point, and the obtained value was compared with the non-coating section and the Vaseline coating section, and the validity was judged. 33 200815042 [Table 9] Table 9 Skin sputum determines a quasi-reported skin reaction 0 No erythema reaction 1 Only a little erythema 2 Red spot is more pronounced than 1 and erythema area is 5〇% 3 Obvious erythema 4 erythema + pimples • Puffy 5 Erythema + small blisters 6 large blisters • necrosis

6. 2 Physical examination The measured value of the transepidermal water evapotranspiration obtained by the vapometer is analyzed by the difference between the patch attachment portion and the non-attachment portion, and the coated portion of each test substance is applied. The value is compared with the non-coating section and the Vaseline coating section 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 among the 20 subjects of each pretreatment agent 〇. 5% sodium lauryl sulfate aqueous solution (SLS) skin irritation, only the skin irritation reference points were 3, 4, The total number of people after 24 hours and 48 hours. Among them, there is no skin thorn of the subject 34 200815042 The number of benchmark points exceeds 4. In the judgment of 24 hours after the sputum, the application of the cream (Example 1) and the cream containing 20% DEG-DA5 (Example 3) was applied to da5 in comparison with the uncoated portion. The subjects who visually evaluated the number of points 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-Μ5 (Examples) 5) The number of visual evaluation points of Vaseline after 5% 5% sodium lauryl sulfate aqueous solution (SLS) is 5 or more, compared with 12 people without coating. Although the result is small, compared with DEG-DA5 and the cream mixed with DEG-DA5, the number is still too large. If the number of points mixed with DEG Μ5 is more than 1 point, It can be concluded that all the mitigating stimuli can be determined. In addition, it can be concluded that the number of people who have strong stimuli as described above and the number of points is 3 or more is also small. According to the result of the Wilcoxon symbol summation test, the job M5 coating site (Example 1) 20% 0£0~〇8 5 cream (Example 3) coated part, 10% DEG-DA5 cream (Example 4) coated part, and Vaseline Compared with the 10 parts coated, the number of points is lower (Ρ < 〇 · 05). The cream mixed with 5% DEG-DA5 (Example 5) # does not show a significant inhibition tendency. Also, mixed 2% The cream of DEG-DA5 (Example 3) was significantly better than the cream mixed with 20% of paraffin wax (Comparative Example 1) and the cream mixed with 2% squalene (Comparative Example 2). The number of stimulating points can be suppressed. In addition, a cream containing 10% DEG-DA5 (Example 4), a milk mixed with 1% of mobile sarcophagus (Comparative Example 3), and milk mixed with 10% squalene In comparison with the cream (Comparative Example 4), the number of stimulation points was also significantly suppressed. 35 200815042 In the judgment after 48 hours, the deg-M5 coating site was mixed with 5% DEG compared with the uncoated portion. -DA5 cream (Example 5) Applicable site, visual inspection [The number of subjects with 3 or more bene points is obviously a minority, followed by a cream mixed with 2% deg - M5 (Example 3) Cream with 20% mobile stone sign (Comparative Example 1). The number of visual evaluation points of Vaseline after SLS attachment is 3 or more, and 8 persons are compared with 15 people without coating. Below, the results are small, but with DEG_ Compared with the cream with DEG-DA5, the number of M5 is still too large. According to the results of the Wilcoxon symbol summation test, the DEG-M5 coating site (Example 1), a cream mixed with 20% DEG-DA5 (Example 3) The application site of the cream (Example 5) coated with 5% DEG-DA5 was coated, and the number of dots was lower than that of the Vaseline coated portion (p < G. 〇 5). , mixed with 2Q% deg-room cream (Example 3) 'With a cream mixed with 20% f-ene (Comparative Example 2), she was significantly more able to suppress the number of stimulation points (Ρ <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. 36 200815042 [Table 10] Table 1G 24h visual judgment (person) no· pre-treatment sample patch point sample 0 1 2 3 4 5 6 1 DEG-DA5 20% cream (Example 3) SLS 13 5 1 1 0 0 0 2 DEG-DA5 20% cream (Example 3) Water 18 2 0 0 0 0 0 3 Squalene 20% cream (Comparative Example 2) SLS 7 3 3 5 2 0 0 4 Squalene 20% cream ( Comparative Example 2) Water 17 3 0 0 0 0 0 5 DEG-DA5 10% cream (Example 4) SLS 11 5 1 2 1 0 0 6 DEG-DA5 10% cream (Example 4) Water 19 1 0 0 0 0 0 7 DEG-DA5 100% (Example 1) SLS 16 3 0 0 1 0 0 8 DEG-DA5 100% (Example 1) Water 18 2 0 0 0 0 0 9 DEG-DA5 5% cream (Example 5) SLS 10 4 2 2 2 0 0 10 DEG-DA5 5% cream (Example 5) Water 19 1 0 0 0 0 0 11 Flowing paraffin 20% cream (Comparative Example 1) SLS 8 4 4 2 2 0 0 12 Flowing paraffin 20% cream (Comparative Example 1) Water 19 0 1 0 0 0 0 13 Squalene 10% cream (Comparative Example 4) SLS 6 4 1 8 1 0 0 14 Squalene 10% milk Cream (Comparative Example 4) Water 19 1 0 0 0 0 0 15 Flowing paraffin 10% cream (Comparative Example 3) SLS 5 5 2 6 2 0 0 16 Flowing paraffin 10% cream (Comparative Example 3) Water 19 0 1 0 0 0 0 17 Vaseline SLS 4 5 6 4 1 0 0 18 Vaseline Water 20 0 0 0 0 0 0 19 No coating SLS 1 4 3 9 3 0 0 20 No coating water 15 3 1 0 1 0 0 37 200815042 [Table 11] Table 11 48h visual judgment (person) no . Pretreatment Sample Patch Sample Points 0 1 2 3 4 5 6 1 DEG-DA5 20% Cream (Example 3) SLS 10 5 1 3 1 0 0 2 DEG-DA5 20% Cream (Example 3) Water 19 1 0 0 0 0 0 3 Squalene 20% cream (Comparative Example 2) SLS 2 5 7 6 0 0 0 4 Squalene 20% cream (Comparative Example 2) Water 18 2 0 0 0 0 0 5 DEG -DA5 10% cream (Example 4) SLS 4 8 2 6 0 0 0 6 DEG-DA5 10% cream (Example 4) Water 20 0 0 0 0 0 0 7 DEG-DA5 1M% (Example 1 SLS 14 4 0 2 0 0 0 8 DEG-DA5 100% (Example 1) Water 19 0 1 0 0 0 0 9 DEG-DA5 5% cream (Example 5) SLS 3 10 4 3 0 0 0 10 DEG-DA5 5% cream (Example 5) Water 19 0 1 0 0 0 0 11 Flowing paraffin 20% cream (Comparative Example 1) SLS 3 5 8 4 0 0 0 12 Flowing paraffin 20% cream (Comparative example) 1) Water 18 2 0 0 0 0 0 13 Squalene 10% cream (Comparative Example 4) SLS 2 5 4 9 0 0 0 14 Squalene 10% cream (Comparative Example 4) Water 19 1 0 0 0 0 0 15 mobile paraffin 10% cream (Comparative Example 3) SLS 4 1 4 11 0 0 0 16 Flowing paraffin 10% cream (Comparative Example 3) Water 18 1 1 0 0 0 0 17 Vaseline SLS 1 6 5 6 2 0 0 18 Vaseline water 19 1 0 0 0 0 0 19 None Coating SLS 0 2 3 13 2 0 0 20 No coating water 17 2 1 0 0 0 0 38 200815042 [Table 12] Safety confirmation test results of pretreatment agent

Measurement of transepidermal water evapotranspiration by machine Table 13, 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 mixed with 2〇% deg_da5 at the SLS attachment site (Example 3), mixed with 〇% DEG-DA5 cream (Example 4). The cream mixed with 20% DEG-DA5 (Example 3), the cream mixed with 1% deG-DA5 (Example 4) for the uncoated part, or the cream mixed with 20% DEG-DA5 (Example 3) It was confirmed that the Vaseline coated portion had a stimulus inhibiting effect 〇 5). After 48 hours of attachment, the increase in TEWL value due to SLS attachment was effectively suppressed in all pretreatment agents compared to the uncoated portion (ρ < 〇 · 05). In particular, DEG-DA5 (Example 1), a cream mixed with 20% DEG_M5 (Example 3) was more effectively inhibited (p<〇5) than the V. sinensis coated site. 39 200815042 [Table 13] Table 13 Transdermal moisture evapotranspiration values of each test substance no· Pretreatment sample patch sample 24h Average 24h stdev 48h Average 48h stdev 1 DEG-DA5 20% cream (Example 3) SLS 5.8 5.2 4.0 3.5 2 DEG-DA5 20°/Γ cream (Example 3) Water 2.4 4.7 LI 3.2 3 Squalene 20% cream (Comparative Example 2) SLS 9.1 8.3 9.8 7.4 4 Squalene 20% cream ( Comparative Example 2) Water 1.3 4.2 0.4 3.7 5 DEG-DA5 10% cream (Example 4) SLS 6.7 7.1 7.1 6.5 6 DEG-DA5 10% cream (Example 4) Water 1.0 2.3 0.8 3.2 7 DEG-DA5 100 % (Example 1) SLS 6.3 14.2 4.9 7.8 8 DEG-Μ5 100% (Example 1) Water 2.4 5.4 1.3 4.3 9 DEG-DA5 5% cream (Example 5) SLS 8.3 10.5 7.5 8.2 10 DEG-Μ5 5 % cream (Example 5) Water 2.3 4.3 1.6 4.2 11 Flowing paraffin 20% cream (Comparative Example 1) SLS 8.9 10.0 6.9 5.1 12 Flowing paraffin 20% cream (Comparative Example 1) Water 0.6 2.9 0.2 3.5 13 Squalene 10% cream (Comparative Example 4) SLS 9.1 7.7 9.5 6.9 14 Squalene 10% cream (Comparative Example 4) Water 1.8 4.4 0.7 3.4 15 Flow paraffin 10% cream (Comparative Example 3) SLS 8.0 7.2 8.3 5.9 16 Flow paraffin 10% cream (Comparative Example 3) Water 1.3 3.6 0.1 1.8 17 Vaseline SLS 9.4 8.1 10.2 5.9 18 Vaseline water 1.4 3.9 1.3 3.1 19 No coating SLS 11.8 8.2 15.8 7.8 20 No coating water 0.4 3.6 0.9 3.5 200815042 13. Summary of the experiment In the case of the osmotic stress-inhibiting effect of the DEG-DA5 and the DEG-DA5-containing cream, 20 subjects with atopic dermatitis and sebum deficiency were examined. As a result, it was found that DEG-DA5 and DEG-containing cream 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. _ _ According to the 24-hour close-fitting test, it is possible to confirm the safety of DEG-DA5 and patients with dermatitis and DE Lin-M5 Weishuang. _ The above results can be transferred to the recorded material mixed with DEG-DA5, which is very suitable for patients with heterozygous skin and patients with poor isolation. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 shows the survival rate of a cream that does not contain lauryl sulphate and is exposed to cells at various concentrations. Figure 2 is a graph showing the survival rate of a cream containing 0.1% sodium lauryl sulfate at various concentrations when exposed to cells. Fig. 3 is the sum of the subjects whose scores indicate 3, 4 after the judgment of 24 hours. Figure 4 is the sum of the subjects whose scores indicate 3, 4 after 48 hours of judgment. Fig. 5 is the average value of the transepidermal water evapotranspiration after 24 hours of attachment (average s D.). Figure 6 is the average value of the transepidermal water evapotranspiration after 48 h of attachment (average health.d.). 41 200815042 [Description of main component symbols]

Claims (1)

200815042 X. Patent application scope: 1. A cosmetic containing dimerized linoleic acid diethyl acrylate. 2. As stated in the claim 1 of the scope=Scope, the ratio of the dimerized linoleic acid and diethylene glycol in the high oleic acid di-di- keel: dimerization- Linoleic acid: diethylene glycol = 〇. 5 moles: h 〇 Mo Er ~ 〇. 8 Mo Er: U Moer. 3. The proportion of the dimerized linoleic acid and diethylene glycol formed in the dimeric linoleic acid diethylene glycol vinegar oligomer as described in claim 1 of the patent application scope is Poly φ linoleic acid: diethylene glycol = 0.5 m molar: 1 · 〇 Mo Er. 4. The cosmetic material described in the above-mentioned article is characterized in that the viscosity of the dimerized linoleic acid diacetate oligomer at 25 ° C is 2,500 to 4,500 mPa · s. The cosmetic according to any one of claims 1 to 4, wherein the dimerized linoleic acid diethylene glycol ester oligomer is a skin irritation mitigating component. The cosmetic according to any one of claims 1 to 5, which is characterized in that it is a moisturizing cosmetic for face or body. The cosmetic according to any one of claims 2 to 6, which is characterized in that it contains 5 to 20% by mass of a dimerized linoleic acid diethylene glycol ester oligomer. 8 A wide range of cosmetic oils containing diethylene linoleate diethylene glycol oligomers. The ratio of dimerized linoleic acid and diethylene glycol is dimerized linoleic acid · · · Glycol = 〇 · 5 Moule: 1.0 Mo Er ~ 〇 · 8 Mo Er: 1 · 〇 Mo Er. 43