JP2009107984A - Oily composition containing dimer dilinoleic acid diethylene glycol oligomer ester - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a stable oily composition containing a dimer dilinoleic acid diethylene glycol oligomer ester having an excellent irritation-relieving effect. <P>SOLUTION: The oily composition comprises a dimer dilinoleic acid diethylene glycol oligomer ester and a divalent alcohol. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an oily composition.

In recent years, with changes in the environment, the number of people with allergic diseases such as atopic dermatitis and those who feel so-called sensitive skin has increased, and these people are sensitive to skin, so redness and itching caused by cosmetics etc. Therefore, cosmetics that are less irritating are required. Therefore, it is required to newly provide an excellent component that relieves such irritation.
As a skin irritation relieving agent such as a surfactant, trehalose monofatty acid ester (Patent Document 1: Japanese Patent Laid-Open No. 10-45560), silicone having a perfluoroalkyl group and a polyoxyalkylene group as side chains (Patent Document 2: Special) Kaihei 6-199629), as an alcohol stimulus mitigating agent, glucose derivatives such as phenylethyl-α-glucoside and phenylethyl-β-glucoside (Patent Document 3: JP-A-8-283121), fat-soluble drugs Polyalkylene glycol as a stimulus-relaxing agent (Patent Document 4: Japanese Patent Laid-Open No. 2002-212024), Trialkyl citrate, polyhydric alcohol, water as a stimulant-relaxing agent for a transdermal external preparation (Patent Document 5: Japanese Patent Laid-Open No. 5-255118) No. Gazette) is disclosed. However, oils that occupy a large blending ratio as cosmetic bases have been studied for safety (Non-patent Document 1: Sugiyama, Ota, “Evaluation of skin irritation of cosmetic oily raw materials”, JCIA Journal. , Japan Industrial Skin Hygiene Association, February 1999, Vol. 41, p.136-142), irritation mitigating action has not been studied.

  As for cosmetics containing esters of dimer acid, Patent Document 6 (Japanese Patent Application Laid-Open No. 2004-2000) has been studied on glossiness, water retention, feel, adhesion to skin and hair, sustainability of touch improvement, and hair setting properties. No. 277285). In Patent Document 6, the stimulus relaxation action is not studied.

Japanese Patent Laid-Open No. 10-45560 JP-A-6-199629 JP-A-8-283121 Japanese Patent Laid-Open No. 2002-212024 JP-A-5-255118 JP 2004-277285 A Sugiyama, Ota, “Evaluation of skin irritation of cosmetic oily raw materials”, JSHI Kyodo Journal, Japan Industrial Skin Hygiene Association, February 1999, Vol. 41, p. 136-142

  An object of the present invention is to provide a stable oil-based composition that is excellent in irritation mitigation using dimerglycol diethylene glycol oligomer ester.

The main configuration of the present invention is as follows.
(1) An oily composition containing dimer dilinoleic acid diethylene glycol oligomer ester and a dihydric alcohol.
(2) The divalent alcohol is one or more of dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, and propylene glycol. (1) The oily composition according to (1).
(3) Dimerdilinoleic acid diethylene glycol oligomer ester is composed of dimerlinoleic acid and diethylene glycol in a ratio of dimerlinoleic acid: diethylene glycol = 0.5 mol: 1.0 mol to 0.8 mol: 1.0 mol (1) or (2) oil-based composition characterized by the above-mentioned.
(4) Dimerlinoleic acid diethylene glycol oligomer ester is characterized in that the ratio of dimerlinoleic acid and diethylene glycol is dimerlinoleic acid: diethylene glycol = 0.5 mol: 1.0 mol (1) Or the oil-based composition of (2) description.
(5) Viscosity at 25 ° C. of dimer dilinoleic acid diethylene glycol oligomer ester is 2,500 to 4,500 mPa · s, (1) or (2) oily composition.
(6) The oil-based composition according to any one of (1) to (5), wherein dimer dilinoleic acid diethylene glycol oligomer ester is a skin irritation reducing component.
(7) The oily composition according to any one of (1) to (6), which is a moisturizing cosmetic for face or body or an external preparation for skin.
(8) A skin irritation alleviating cosmetic comprising the oily composition according to (7).

1. The stable oil-based composition excellent in the stimulus relaxation effect containing dimer dilinoleic acid diethylene glycol oligomer ester was able to be provided.
2. Since the oil-based composition of the present invention is excellent in the irritation mitigating effect, the use of the oil-based composition of the present invention can suppress the skin barrier destruction caused by the stimulating substance. Since the rough skin is improved and the skin is protected by suppressing the barrier destruction, it is possible to provide an oily composition excellent in the rough skin improving effect and the moisturizing effect.
3. By using the oily composition of the present invention, aging can be prevented because it maintains the health of the skin by an excellent moisturizing effect against aging caused by drying accompanying skin irritation.
4). The oil-based composition of the present invention is an ointment-like cosmetic, an ointment-like quasi-drug, an ointment-like external preparation for skin, a lip balm, or an oil-based gel-like cosmetic gelled with an oil-based thickener, an oil-based gel-like pharmacy. It can be applied to external products, oil-based gel external preparations, oil-based gel lip balm and the like. Since the oily composition of the present invention has a remarkable irritation mitigating effect and a rough skin preventing effect, it is suitable for a moisturizing cosmetic and a rough skin improving external medicine. The present invention is suitable as an irritating cosmetic.

Details of the present invention will be described below.
The present invention is based on an oily composition containing dimer dilinoleic acid diethylene glycol oligomer ester and a dihydric alcohol. A stable oily composition with excellent skin irritation mitigation.
Dimerdilinoleic acid diethylene glycol oligomer ester is preferably composed of dimerlinoleic acid and diethylene glycol in a ratio of dimerlinoleic acid: diethylene glycol = 0.5 mol: 1.0 mol to 0.8 mol: 1.0 mol, In particular, 0.5 mol: 1.0 mol is preferable.

[Dimer dilinoleic acid diethylene glycol oligomer ester]
Dimerdilinoleic acid diethylene glycol oligomer ester (hereinafter sometimes referred to as “DEG-DA”) used in the present invention is obtained by esterifying dimerlinoleic acid and diethylene glycol. The viscosity of dimerlinoleic acid diethylene glycol oligomer ester at 25 ° C. is preferably 2,500 to 4,500 mPa · s, and dimerlinoleic acid diethylene glycol oligomer ester is a skin irritation relieving component.
Although the compounding quantity of the dimer dilinoleic acid diethylene glycol oligomer ester mix | blended with the oil-based composition material of this invention is not necessarily restrict | limited, 10-80 mass% is preferable with respect to cosmetics whole quantity.

<Dimer linoleic acid>
Dimer linoleic acid is a dibasic acid generally called dimer acid, and is a linole obtained by polymerizing unsaturated fatty acids such as two molecules of linoleic acid [(9Z, 12Z) -octadeca-9,12-dienoic acid]. It is a dimer of acid. The product of the polymerization reaction of linoleic acid includes, in addition to the dimer of linoleic acid, unreacted linoleic acid and trimer, and a highly polymerized linoleic acid polymer. The content of the dimer of linoleic acid can be increased to 90% by mass or more by molecular distillation. Moreover, hydrogen can be added to the dimer unsaturated bond of the obtained linoleic acid to stabilize it. A hydrogenated dimer of these linoleic acids is generally called hydrogenated dimer acid. Any of these dimer acids and hydrogenated dimer acids can be used as the dimer linoleic acid used for the synthesis of the diethylene glycol oligomer oligomer ester of the present invention, but from the viewpoint of oxidation stability, water can be used. It is more preferable to use an additive dimer acid. As the hydrogenated dimer acid, commercially available products such as PRIKOL 1006, PRIPOL 1009, PRIPOL 1025, etc. manufactured by Unikema 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 commercially available as an organic synthesis raw material.

  Dimerlinoleic acid diethylene glycol oligomer ester can be obtained by polymerizing dimerlinoleic acid and diethylene glycol by an esterification reaction. Although the esterification method is not particularly limited, for example, paratoluenesulfonic acid, sulfuric acid, hydrochloric acid, methanesulfonic acid or the like is used as a non-catalyst or a catalyst, and toluene, hexane, heptane or the like is used as a solvent-free or solvent. What is necessary is just to react at the temperature of 260 degreeC.

The ratio of dimer linoleic acid and diethylene glycol, which is composed of dimer linoleic acid and diethylene glycol, is preferably 0.5 mol: 1.0 mol to 0.8 mol: 1.0 mol. When the ratio of dimer dilinoleic acid: diethylene glycol is 0.5 mol: 1.0 mol, the oligomer has a distribution centered on dimer diglycol bonded to both ends of dimer dilinoleic acid. When the ratio of dimer linoleic acid: diethylene glycol is 0.8 mol: 1.0 mol, an oligomer having a distribution centering on an ester bond between four dimer linoleic acids and five diethylene glycols is obtained.
In any case, since diethylene glycol is excessive as compared with dimer linoleic acid, the carboxyl group hardly remains, and the functional group remaining at the terminal of the oligomer becomes almost a hydroxyl group. When the molar ratio of dimer linoleic acid and diethylene glycol approaches 1, the degree of polymerization increases and the viscosity of the oil increases, which is not preferable. Further, if the molar concentration of dimer linoleic acid is excessive as compared with diethylene glycol, the remaining functional group becomes a carboxyl group, which is not preferable in terms of safety.

In particular, the ratio of dimer dilinoleic acid and diethylene glycol is dimer dilinoleic acid: diethylene glycol = 0.5 mol: 1.0 mol, and the viscosity at 25 ° C. is 2,500-4,500 mPa · s. Dimerdilinoleic acid diethylene glycol oligomer ester was found to have a low skin permeability of the drug, an irritation mitigating action and a transdermal moisture transpiration inhibiting action, and a high anti-rough skin effect. It was confirmed that this effect was significantly different from that of the similar dimer dilinoleic acid diethylene glycol oligomer ester.
In addition, although patent document 6 is examining the cosmetics which mix | blended various dimer acid diethylene glycol oligomer ester, the irritation | stimulation mitigation effect | action is not examined. JP-A-2004-256515 discloses dimer acid diethylene glycol oligomer ester (dimer acid: diethylene glycol = 1: 0.5) / mixed alcohol (behenyl alcohol: isostearyl alcohol: phytosterol = 9: 1: 1) ester. However, dimer linoleic acid diethylene glycol oligomer ester in which the charging ratio of the present invention is dimer dilinoleic acid: diethylene glycol = 0.5 mol: 1.0 mol to 0.8 mol: 1.0 mol is not disclosed. They have different polarities, and they are completely different in physical properties and usability.

[Divalent alcohol]
Examples of the dihydric alcohol blended in the oily composition of the present invention include dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, and propylene glycol. Etc.

[Usage]
The oily composition of the present invention includes an ointment-like cosmetic, an ointment-like quasi-drug, an ointment-like external preparation for skin, a lip balm, or an oil-based gel-like cosmetic gelled with an oil-based thickener, an oily gel-like pharmacy. External products, oily gel-like skin external preparations, oily gel-like lip balm and the like. Since the oily composition of the present invention has a remarkable irritation mitigating effect and a rough skin preventing effect, it is suitable for a moisturizing cosmetic and a rough skin improving external medicine. Suitable as an alleviating cosmetic.

[Other ingredients]
The oily composition of the present invention includes a triglyceride oil, an ester oil, a hydrocarbon oil, a silicone oil, a higher fatty acid, a higher alcohol, an anionic surfactant, and a cationic surfactant depending on the use, purpose of use, dosage form, and the like. , Amphoteric surfactants, nonionic surfactants, oil thickeners, preservatives, sugars, sequestering agents, powder components, UV absorbers, UV blockers, moisturizers such as hyaluronic acid, perfume, pH A regulator or the like can be contained. Vitamins, skin activators, blood circulation promoters, resident bacteria control agents, active oxygen scavengers, anti-inflammatory agents, whitening agents, bactericides, and other medicinal and physiologically active components can also be included.

Examples of the triglyceride oil include tri (2-ethylhexanoic acid) glyceryl, tri (caprylic acid / capric acid / myristic acid / stearic acid) glyceryl, animal and vegetable oils, and the like.
Examples of ester oils include cetyl 2-ethylhexanoate and isotridecyl isononanoate.
Examples of the hydrocarbon oil include squalane and liquid paraffin.
Examples of the silicone oil include dimethylpolysiloxane, methylphenylpolysiloxane, and cyclodimethylpolysiloxane.

  Examples of the higher alcohol include linear alcohols such as lauryl alcohol, stearyl alcohol, cetyl alcohol, and cetostearyl alcohol, and branched chain alcohols such as monostearyl glycerin ether, lanolin alcohol, cholesterol, phytosterol, and octyldodecanol.

Examples of the anionic surfactant include fatty acid salts such as sodium laurate, higher alkyl sulfates such as sodium lauryl sulfate, alkyl ether sulfates such as POE lauryl sulfate triethanolamine, N-acyl sarcosine acid, sulfosuccinate N-acyl amino acid salts and the like.
Examples of the cationic surfactant include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride, benzalkonium chloride, and benzethonium chloride.

Examples of amphoteric surfactants include betaine surfactants such as alkyl betaines and amide betaines.
Examples of nonionic surfactants include sorbitan fatty acid esters such as sorbitan monooleate, and hardened castor oil derivatives.
Examples of oil thickeners include dextrin palmitate, microcrystalline wax, (behenic acid / eicosannic acid) glyceryl, silica, silylated silica, and the like.
Examples of preservatives include methyl paraben and ethyl paraben.
Examples of the sequestering agent include edetate such as disodium ethylenediaminetetraacetate, edetic acid, and sodium edetate.
In order to suppress stickiness and color, powder components include, for example, talc, kaolin, mica, silica, zeolite, polyethylene powder, polystyrene powder, cellulose powder, inorganic white pigment, inorganic red pigment, titanium oxide coated Mention may be made of pearl pigments such as mica, titanium oxide coated talc and colored titanium oxide coated mica, and tar dyes such as red 201 and red 202.

Examples of the ultraviolet absorber include paraaminobenzoic acid, phenyl salicylate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, 2,4-dihydroxybenzophenone, and the like.
Examples of the ultraviolet blocking 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, sodium lactate, pyrrolidone carboxylic acid, cyclodextrin, glycerin and the like.
Medicinal ingredients include, for example, vitamin A oils such as vitamin A oil and retinol, vitamin B2 such as riboflavin, B6 such as pyridoxine hydrochloride, pantothenic acids such as calcium pantothenate, vitamin D2 such as vitamin D2 and cholecalciferol And vitamins such as vitamin E such as α-tocopherol, tocopherol acetate, and DL-α-tocopherol nicotinate.

In addition, skin activators such as royal jelly and beech tree extract, capsaicin, gingeron, cantalis tincture, ictamol, caffeine, tannic acid, γ-oryzanol and other blood circulation promoters, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, azulene, etc. Anti-inflammatory agents, amino acids such as arginine, serine, leucine and tryptophan, maltose sucrose condensate of resident bacteria control agent, lysozyme chloride and the like.
In addition, chamomile extract, parsley extract, wine yeast extract, grapefruit extract, honeysuckle extract, rice extract, grape extract, hop extract, rice bran extract, loquat extract, buckwheat extract, yakuinin extract, assembly extract, merilot extract, birch extract, peonies extract, savonso Extract, loofah extract, red pepper extract, lemon extract, gentian extract, perilla extract, aloe extract, rosemary extract, sage extract, thyme extract, tea extract, seaweed extract, cucumber extract, clove extract, maronier extract, hamamelis extract, mulberry extract, etc. Various extracts can be blended.

[Test on Dimerlinoleic Acid Diethylene Glycol Oligomer Ester (DEG-DA)]
Below, the manufacture example regarding the dimer linoleic acid diethylene glycol oligomer ester which is one of the main components of the emulsion composition of this invention, and confirmation tests, such as an irritation relaxation effect and safety, are described. In addition, dimer dilinoleic acid diethylene glycol oligomer ester may be described as “DEG-DA” hereinafter.

[Example 1 of dimerged linoleic acid diethylene glycol oligomer ester (DEG-DA5)]
Dimer dilinoleic acid diethylene glycol oligomer ester (dimer dilinoleic acid: diethylene glycol = 0.5 mol: 1.0 mol) is designated as Example 1 of DEG-DA and its production is shown.
Into a 1 L reactor equipped with a stirrer, a thermometer, and a gas introduction tube was charged 349 g (0.6 mol) of dimer linoleic acid (manufactured by Unikema, PRIPOL 1025) and 127 g (1.2 mol) of diethylene glycol in a nitrogen stream. It is heated to 210-220 ° C., and the esterification reaction is carried out for 12 hours while distilling off the generated water, and dimerlinoleic acid diethylene glycol oligomer ester (dimermarinoleic acid: diethylene glycol = 0.5: 1.0) (hereinafter “ 416 g) (sometimes referred to as “DEG-DA5”) as a pale yellow, highly viscous oil.
The physical properties of the obtained 3 lots of oil are shown in Table 1 below.

[Example 2 of diethylene glycol diethylene glycol oligomer ester (DEG-DA8)]
Dimer dilinoleic acid diethylene glycol oligomer ester (dimer dilinoleic acid: diethylene glycol = 0.8 mol: 1.0 mol) is designated as Example 2 of DEG-DA and its production is shown.
A 1 L reactor equipped with a stirrer, a thermometer, and a gas introduction tube was charged with 372 g (0.64 mol) of dimerlinoleic acid (manufactured by Unikema, PRIPOL 1025) and 84.8 g (0.8 mol) of diethylene glycol, and nitrogen. It is heated to 210-220 ° C. in an air stream, and the esterification reaction is carried out for 14 hours while distilling off the generated water, and dimerlinoleic acid diethylene glycol oligomer ester (dimerlinoleic acid: diethylene glycol = 0.8: 1.0) ( In the following, 375 g (sometimes referred to as “DEG-DA8”) was obtained as a pale yellow high-viscosity oil.
The physical properties of the obtained oil are shown in Table 2 below.

<Drug skin penetration test>
Drug skin permeability was evaluated using DEG-DA5, a commercially available dimer acid ester, and dimer diol ester as oil agents.
1. Sample A drug skin penetration test was conducted using a sample obtained by dissolving DEG-DA5 shown in Table 3 as an oil agent and dissolving ibuprofen (Sigma) at 1% in a commercially available dimer acid ester or dimer diol ester.

2. Test Method Yucatan Micropig dorsal skin (5-month-old female, Nippon Charles River Co., Ltd.) frozen at -80 ° C. for 30 minutes at room temperature to remove excess fat on the skin, about 2 cm square Cut and used for testing.
The skin was sandwiched between cells with an effective area of 0.95 cm ² and 0.2 ml of sample was applied. After 48 hours, the skin surface sample was removed by wiping, and the skin was crushed in a methanol / 0.1% phosphoric acid aqueous solution mixture (70:30) using an acupuncture and homogenizer to extract ibuprofen, and ibuprofen in the skin was extracted. The amount was measured by HPLC. Table 3 shows the measurement results.
2.1 HPLC measurement conditions Detector: UV absorptiometer LC-10AD (manufactured by Shimadzu Corporation)
Measurement wavelength: 220 nm
Column: TSK-GEL ODS-80Ts 4.6 mm × 150 mm (Tosoh Corporation)
Mobile phase: methanol: 0.1% aqueous phosphoric acid solution = 75:25
Flow rate: 1 ml / min 2.2 Data processing CLASS-VP (manufactured by Shimadzu Corporation) was used to create another calibration curve from the peak area of ibuprofen, and the concentration was determined by calculation.

3. Results Table 3 shows the measurement results.
Ibuprofen is generally used as an index for transdermal absorption. If absorption of ibuprofen into the skin is small, the effect of suppressing the absorption of stimulating substances is excellent.
When ibuprofen was dissolved in DEG-DA5, the amount of ibuprofen in the skin after 48 hours was 21 μg, whereas in the case of commercially available dimer acid ester and dimer diol ester, the amount of ibuprofen was 37 μg to 70 μg. Among dimer acid esters and dimer diol esters, DEG-DA5 as an oil agent is extremely excellent in the effect of suppressing ibuprofen skin permeation and is excellent in the absorption suppression effect of stimulating substances. Among commercial oils, LUSPLAN DD-DHR: Nihon Seika Co., Ltd. dimer linoleyl hydrogenated rosin condensate (ibuprofen amount 37 μg), LUSPLAN DD-DA7: Nihon Seika Co., Ltd. dimer linoleic acid dimer dilino Rail (ibuprofen amount 42 μg) also has a lower absorption of ibuprofen, but both oils are highly viscous, sticky, and glaring, making it difficult to use in moisturizing cosmetics.

< Irritation relaxation test using collagen gel method>
DEG-DA5, DEG-DA8 and the commercially available oil agent were compared in terms of the stimulating and mitigating action.
1. Test substance The oil agent shown in Table 4 is added as it is, or 0.5% by mass, 0.8% by mass and 1.2% by mass of lauric acid, which is reported to be irritating in animals and humans, are added to the oil agent. The test substance was used.

2. Test Method 2.1 Preparation of Collagen Gel Prepare a mixture of type I-AC collagen (Koken) aqueous solution, normal human fibroblasts (manufactured by CAMBLEX) in a medium, and an appropriate amount of reconstituted solution with a stirrer. The final concentration of type I-AC collagen (Koken) is 0.1% by mass, the final concentration of normal human fibroblasts (CAMBLEX) is 4.0 × 10 ⁵ cells / mL, and the 6-well culture insert (manufactured by FALCON) is used. 1 mL was added dropwise. The culture medium was DMEM + 10% FBS. The collagen gel was cultured for about 16 hours (12-24 hours).
2.2 Application of test substance to collagen gel Add 0.5g, 0.8%, 1.2% by weight of lauric acid and 1g of test substance without addition to the collagen gel prepared in 2.1 And exposed for 24 hours. After the exposure for 24 hours, the test substance was removed, and the cell viability by MTTassay was measured and calculated, and the dependence of the cell viability on the lauric acid concentration was examined.

3. Results The results are shown in Table 4.
Dimer dilinoleic acid diethylene glycol oligomer ester (dimer dilinoleic acid: diethylene glycol = 0.5: 1.0) has a cell viability of about 80% even when 1.2% by mass of lauric acid is added, which is effective in reducing the stimulation. It turned out to be very good. There is data that the cell survival rate is improved by adding 0.5% lauric acid compared with no lauric acid added, but 95% → 104% with DEG-DA5, 72% → 78% with LUSPLAN DD-IS), This is due to data variation.

<Irritation relaxation test using cells>
A cream supplemented with sodium lauryl sulfate was applied to normal human fibroblasts, and the effect of the cream on mitigating the stimulation of sodium lauryl sulfate was examined.
1. Test cream Each cream, and 10% lauryl sulfate was used for each cream, using the creams of Test Example 13, Reference Comparative Example 1 and Reference Comparative Example 2 which were creams containing DEG-DA5 having the formulation shown in Table 5. A sodium aqueous solution was added and mixed to adjust the content of sodium lauryl sulfate in the cream to 0.1%.

2. Test Method The test cream was mixed and diluted in the medium.
Normal human fibroblasts were seeded in a 96-well plate at 3.5 × 10 ³ and cultured for 5 days.
In a confluent state, the medium was changed to a mixed and diluted medium so that the concentration of the test cream was 0.156% to 20%, and the cells were exposed to the test cream.
Cell viability was determined using MTT assay after 20 hours exposure.

3. Results Fig. 1 shows the survival rate when a cream containing no sodium lauryl sulfate was exposed to cells at various concentrations, and when a cream containing sodium lauryl sulfate at a concentration of 0.1% was exposed to cells at various concentrations. The survival rate is shown in FIG.
As shown in FIG. 1, in each case, when the cream containing no sodium lauryl sulfate was exposed to cells at various concentrations, as the concentration of the cream in the medium increased from 0.156% to 20%, the survival rate was about It decreased almost similarly from 80% to about 60%.
On the other hand, as shown in FIG. 2, when the cream containing sodium lauryl sulfate at a concentration of 0.1% was exposed to cells at various concentrations, the concentration of the cream in the medium increased from 0.156% to 10%. Even in this case, the cell viability in each case decreased from about 80% to about 70% almost similarly.
However, when the concentration of the cream in the medium was 20%, the cream of Test Example 1 containing sodium lauryl sulfate at a concentration of 0.1% maintained the cell viability of 54%, but the concentration of 0.1% In the creams of Reference Comparative Examples 1 and 2 containing sodium lauryl sulfate, the cells were almost killed (cell survival rate 1%).
Therefore, the cream of Test Example 1 is particularly excellent in the effect of alleviating irritation of sodium lauryl sulfate.

< Irritation mitigation test by human patch test>
The effect of alleviating irritation of sodium lauryl sulfate on the cream containing DEG-DA5, cream containing DEG-DA5 as an oil (Test Example 1), cream containing liquid paraffin and liquid paraffin (Reference Comparative Example 1) Evaluated by testing.
1. Pre-treated test article DEG-DA5, liquid paraffin, and the cream of Test Example 1 and Reference Comparative Example 1 having the composition shown in Table 5 were applied to the skin before applying the patch test test article.
2. Patch test test article A 0.5% sodium lauryl sulfate aqueous solution and sterilized water (control) were used as patch test test articles.

3. Subjects Twelve healthy 20 to 50 generations who showed a false positive reaction or higher with a 0.1% to 0.5% aqueous solution of sodium lauryl sulfate in a past patch test and did not show skin symptoms such as itching and rash on the applied site ( 3 males and 9 females) were used.
4). Test Method A pretreated test product was applied, and then a 24-hour occlusion patch test was performed using the patch test test product as a specimen. An area of 10 mm × 30 mm was marked in advance on the inner side of the upper arm of the subject at 3 and 2 locations (5 locations on both arms), and the transdermal moisture transpiration at each location was measured using a Delfin vapometer. Next, 10 μL of 4 pretreated test products were applied one by one and allowed to blend for about 5 to 10 minutes (the remaining 1 site was not applied with the pretreated test product). After confirming that the pre-treated test product became familiar with the skin, about 20 μL of the patch test test product was dropped on the filter paper on the fin chamber for human body sticking test (diameter 11 mm, Taisho Pharmaceutical Co., Ltd.), and immediately on the 5 marking locations of the test subject. Time occlusion was applied. After removing the fin chamber, the skin reaction was visually observed according to the criteria shown in Table 6 at 2 hours (24 hours after application) and 24 hours after the next day (48 hours after application). At the same time, the amount of transdermal moisture transpiration was measured.

5). Visual determination results Table 7 shows the visual determination results.
In the case of no pretreatment test article application, the skin irritation score average value 0.750 24 hours after application of a 0.5% sodium lauryl sulfate aqueous solution, but by applying the pretreatment test article, the skin irritation score average value is To reduce. In particular, DEG-DA5 (0.208) and the cream of Test Example 1 (0.167) have a significant irritation mitigating effect, and the average value of skin irritation score is 2/10 to 3 compared to the case where the pretreated test article is not applied. / 10. The cream of Reference Comparative Example 1 (0.458) is 6/10 compared to the untreated pre-treated product, and an irritation mitigating effect is observed, but the liquid paraffin (0.667) is untreated with the pre-treated test product. 9/10 compared to the above, and the stimulus relaxation effect is hardly recognized.

In the case where the pretreatment test product was not applied, the skin irritation score average value 48 hours after application of a 0.5% sodium lauryl sulfate aqueous solution was 1.083. As for the pretreatment test product application effect, DEG-DA5 (0.333) is 3/10 compared to the pretreatment test product non-application, and a significant irritation mitigating effect is observed. The cream of Test Example 1 (0.583) is 5/10 compared to the pre-treated test article non-applied, and an irritation mitigating effect is observed. The cream of Reference Comparative Example 1 (0.792) is 7/10 compared to the pre-treated test article non-applied, and although it is weak, an irritation mitigating effect is observed. On the other hand, when liquid paraffin is applied, the average value of the skin irritation score is 1.292, which is 12/10 as compared to the case where the pretreated test article is not applied, which is a result of slightly enhancing the stimulation of sodium lauryl sulfate.
It was confirmed that DEG-DA5 and the cream of Test Example 1 containing DEG-DA5 had a significant irritation mitigating action.

6). Table 7 shows the results of measuring the amount of transdermal moisture transpiration.
In the case where the pretreatment test product was not applied, the transdermal moisture transpiration amount was 24 hours after application of the 0.5% sodium lauryl sulfate aqueous solution. The amount of transdermal moisture transpiration when sterilized water is applied is 3, which clearly indicates that the skin barrier is destroyed and the rough skin is progressing. By applying DEG-DA5 and the cream of Test Example 1 in advance, the transdermal moisture transpiration after 24 hours of application of a 0.5% sodium lauryl sulfate aqueous solution was 5 and 4, respectively, and the pretreatment test article was not applied 8 Is suppressed to about half.
Therefore, the stimulus relaxation effect and the rough skin prevention effect are exhibited. When the cream of Reference Comparative Example 1 was applied in advance, the transdermal moisture transpiration amount after 24 hours of application of a 0.5% sodium lauryl sulfate aqueous solution was 7, which was almost the same as that of the pretreated test article uncoated 8, and the stimulation was alleviated. The effect and the rough skin prevention effect are hardly recognized. When liquid paraffin was applied in advance, the transdermal moisture transpiration amount after 24 hours of application of a 0.5% sodium lauryl sulfate aqueous solution was 11, which is about 1.4 times that of the pretreatment test article 8 without application. Irritation and rough skin are enhanced.

  In the case where the pretreatment test product was not applied, the transdermal moisture transpiration amount after 48 hours of application of the 0.5% sodium lauryl sulfate aqueous solution increased to 12, and the rough skin progressed. By applying DEG-DA5 and the cream of Test Example 1 in advance, the transdermal moisture transpiration after 48 hours of application of a 0.5% sodium lauryl sulfate aqueous solution was 4, 1/3. And the difference with the amount 2 of percutaneous water transpiration | evaporation 48 hours after no pre-processing test article application | coating and sterilization water sticking is small. Accordingly, the rough skin does not proceed and is slight, and the rough skin is remarkably suppressed. When the cream of Reference Comparative Example 1 was applied in advance, the amount of transdermal moisture transpiration 48 hours after application of the 0.5% sodium lauryl sulfate aqueous solution was 8, which was 2/3 of the pretreated test article non-applied 12. Although the rough skin prevention effect is recognized, it is not so remarkable as DEG-DA5 and the cream of Test Example 1. When liquid paraffin was applied in advance, the transdermal moisture transpiration amount after 48 hours of application of 0.5% sodium lauryl sulfate aqueous solution was 15, which was about 1.3 times that of the pretreated test article 12 without application. Irritation and rough skin are enhanced.

  It was confirmed that DEG-DA5 and the cream of Test Example 1 containing DEG-DA5 had a significant irritation mitigating action and rough skin prevention effect.

<Irritation mitigation effect test by patch test of 20 men with atopic dermatitis or sebum deficiency>
DEG-DA5 (DEG-DA5), a cream containing DEG-DA5, was verified by a human patch test on the stimulating effect on subjects with atopic dermatitis or sebum deficiency.

1. Subject 1-1 Age Composition Twenty men from 19 to 45 years old had an average age of 27.9 years. There was no dropout during the test.
1-2 Subject skin disease The doctor in charge of the diagnosis made a diagnosis of the subject's symptoms in advance. There were 11 cases of atopic dermatitis and 9 cases of sebum deficiency. The subjects with atopic dermatitis had 7 mild cases, 2 mild to moderate cases, and 2 moderate cases.

2. Pre-treated test products 3 types of creams containing DEG-DA5 and DEG-DA5, 4 types of creams containing liquid paraffin and squalane generally used as cosmetic oils as reference comparative examples, and moisturizing prescribed in dermatology Vaseline was used as a pretreated test product as a representative of the agent. No treatment was the control.
1. 1. Cream of Test Example 1 containing 20% DEG-DA5 2. Cream of Test Example 2 containing 10% of DEG-DA5 3. Cream of Test Example 3 containing 5% DEG-DA5 4. Cream of Reference Comparative Example 1 containing 20% liquid paraffin 5. Cream of Reference Comparative Example 3 containing 10% liquid paraffin 6. Cream of Reference Comparative Example 2 containing 20% squalane. 7. Cream of Reference Comparative Example 4 containing 10% squalane. DEG-DA5
9. Vaseline (manufactured by Nikko Rica)
10. No treatment (control)
The cream formulations of Test Example 1 and Reference Comparative Examples 1 and 2 are shown in Table 5. Table 8 shows the formulations of the creams of Test Examples 4 and 5 and Reference Comparative Examples 3 and 4.

Pretreatment agent safety test A 24-hour closed patch test was conducted for the safety confirmation test of the pretreatment agent. Visual evaluation results of 4 test substances affixed [DEG-DA5 blended 20% cream (Test Example 1), liquid paraffin 20% blended cream (Reference Comparative Example 1), squalane 20% blended cream (Reference Comparative Example 2), petrolatum] Is shown in Table 8. In contrast to the results of all negative results for DEG-DA5 cream and liquid paraffin cream in each judgment time, one test subject showed a score of 3 for squalane cream combination, 24 hours for test subjects who showed a score of 1 for petrolatum. One person was admitted. However, the irritation response decreased on the 7th day at 48 h, and it was confirmed that it was not an allergic symptom. From the above results, it was confirmed that the 4 test substances had no apparent primary skin irritation as a result of 24 h occlusion pasting.

3. Patch Test Test Article In order to evaluate the effect of alleviating primary skin irritation, a 0.5% sodium lauryl sulfate (Kanto Chemical) aqueous solution (hereinafter referred to as SLS) was used as a skin test substance as a patch test test article. As a control, sterilized water was simultaneously attached to each application part.

4). Modified Closed Patch Test Test Method Ten regions of 10 mm × 30 mm are set on the back of the subject using a plastic frame, and a certain amount of cream of DEG-DA5, petrolatum and Test Examples 1-5 and Reference Comparative Examples 1-4. (About 15 μL) was weighed with a micro-dispensing device, and one kind of pretreated test article was applied to one place. There were nine pretreated test article application areas, and the remaining one area was untreated as a control.
Thereafter, a closed patch test was carried out for 24 hours using 0.5% sodium lauryl sulfate aqueous solution (SLS), which is a skin irritant, and sterilized control water as a patch test article. A Taisho Pharmaceutical fin chamber was used for the patch test.
The application part was selected at five locations on the left and right sides of the spine. In the application area, the doctor in charge of the examination looked at the back of the subject and applied the pretreated test article and applied the patch bond while avoiding the inflamed area such as erythema.

5). Evaluation items and evaluation time The following two items were evaluated.
1) Skin findings: Visual determination of skin changes by patch test (Test Day 2, Day 3, Day 7)
2) Physical examination: Transepidermal water transpiration with vapometer (Delfin) (Test Day 2, Day 3)

6). Evaluation method 6.1 Skin findings Visual judgment was performed by the doctor in charge of the test according to the criteria for skin irritation (Table 9). Judgment results were calculated as average values instead of scores. The effectiveness was judged by comparing the obtained values with the uncoated part and the petrolatum coated part.

6.2 Physical examination
The transepidermal moisture transpiration measurement value obtained using the vapometer was obtained by subtracting the non-applied site value from each patch adhesive applied site for analysis. The effectiveness was judged by comparing the value of each test substance application part, the non-application part, and the petrolatum application part.

7). Visual determination by dermatologist The doctor in charge of the test visually determined on the 7th day after 24 hours and 48 hours after application according to the skin irritation criteria. Table 10 shows the results of visual judgment 24 hours after application, and Table 11 shows the results of visual judgment 48 hours after application. 3 and 4 show only the skin irritation reference scores 3 and 4 out of the 20 0.5% sodium lauryl sulfate aqueous solution (SLS) skin irritation scores in each pretreatment agent, 24 hours and 48 hours later. The total number of people. None of the subjects had a skin irritation reference score greater than 4.
In the 24-hour determination, compared with the non-application site, DEG-DA5 application site, DEG-DA5 20% combination cream (Test Example 1) fewer subjects clearly showed a visual evaluation score of 3, 4 or more at the application site, DEG-DA5 10% combination cream (Test Example 2) and DEG-DA5 5% combination cream (Test Example 3). Petrolatum had fewer results when compared to 5 subjects and 12 subjects who had not applied the sample, with a visual evaluation score of 3 or 4 or higher when 0.5% sodium lauryl sulfate aqueous solution (SLS) was applied. DEG-DA5 Compared with the cream containing DEG-DA5, the number was large. When the DEG-DA5 formulation is viewed as a total score of score 1 or higher, it is recognized that the stimulation is alleviated as a whole, and further, as described above, it is recognized that the score of 3 or higher is strong.
As a result of Wilcoxon signed rank sum test, petrolatum at DEG-DA5 application site (DEG-DA5), DEG-DA5 20% combination cream (Test Example 1) application site, DEG-DA5 10% cream (Test Example 2) application site The score was significantly lower than the application site (p <0.05). In the DEG-DA5 5% combination cream (Test Example 3), although there was a tendency to suppress, there was no significant difference. In addition, DEG-DA5 20% combination cream (Test Example 1) has significantly higher stimulation score than liquid paraffin 20% combination cream (Reference Comparative Example 1) and squalane 20% combination cream (Reference Comparative Example 2)). It was suppressed. Furthermore, DEG-DA5 10% combination cream (Test Example 2) has a significantly reduced stimulation score compared to 10% liquid paraffin combination cream (Reference Comparative Example 3) and squalane 10% combination cream (Reference Comparative Example 4). It had been.

In the 48-hour judgment, compared to the non-application site, DEG-DA5 application site, DEG-DA5 5% combination cream (Test Example 3) fewer subjects clearly showed a visual evaluation score of 3, 4 or more at the application site, DEG-DA5 20% combination cream (Test Example 1) and liquid paraffin 20% combination cream (Reference Comparative Example 1). Vaseline showed fewer results when compared with 8 subjects and 15 subjects who had no application on the SLS sticking visual evaluation score of 3 or 4, but compared with DEG-DA5 and DEG-DA5 combination cream. There were many people.
As a result of Wilcoxon signed rank sum test, petrolatum at DEG-DA5 application site (DEG-DA5), DEG-DA5 20% combination cream (Test Example 1) application site, DEG-DA5 5% cream (Test Example 3) application site The score was significantly lower than the application site (p <0.05). Further, DEG-DA5 20% combination cream (Test Example 1) had a significantly suppressed irritation score as compared to squalane 20% combination cream (Reference Comparative Example 2) (p <0.05).
The 7th day determination was performed to confirm the presence or absence of allergic symptoms. As a result, only one test subject showed a score of 1 or more, which was the SLS application site in the non-application area, and there was no effect of the pretreatment agent.

8). Transepidermal moisture transpiration by instrument measurement Tables 13, 5 and 6 show the average transepidermal moisture transpiration values of each test substance. 24 hours after application, the SLS application site where the tendency to suppress TEWL value due to irritation was observed in DEG-DA5, DEG-DA5 20% combination cream (Test Example 1), and DEG-DA5 10% combination cream (Test Example) 2). DEG-DA5 20% cream (Test Example 1), DEG-DA5 10% cream (Test Example 2) was applied to the non-application site, and DEG-DA5 20% cream (Test Example 1) was applied to the petrolatum application site. Also had a significant stimulus-suppressing effect (p <0.05). 48 hours after application, the increase in TEWL due to application of SLS was significantly suppressed in all pretreatment agents compared to the uncoated area (p <0.05). In particular, DEG-DA5 (DEG-DA5) and DEG-DA5 20% combination cream (Test Example 1) were significantly suppressed (p <0.05) even when compared with the petrolatum application site.

13. Summary of Subject-Evaluation Tests on DEG-DA In this test, the stimulant component penetration inhibitory effect of the cream containing DEG-DA5 and DEG-DA5 was verified for 20 patients with atopic dermatitis and sebum deficiency. . As a result, the tendency for DEG-DA5 and DEG-DA5 combination cream to suppress the stimulation of SLS in a concentration-dependent manner was recognized, suggesting an approximate concentration that exerts an effect when used in humans.
In addition, safety of DEG-DA5 and DEG-DA5 combination cream was confirmed by a 24-hour closed patch test for patients with atopic dermatitis and those with sebum deficiency.
From the above results, the cosmetics containing DEG-DA5 are suitable for use by people with atopic dermatitis and those with sebum deficiency with reduced barrier function.

[Examples concerning oil-based composition]
Examples and comparative examples relating to oil-based compositions containing dimerlinoleic acid diethylene glycol oligomer ester (DEG-DA) and dihydric alcohol are described below.

<Preparation and Stability Evaluation Test of Oil-Based Composition Containing Dimerlinoleic Acid Diethylene Glycol Oligomer Ester>

Preparation of Oily Composition The oily compositions of Examples 1 to 5 and Comparative Examples 1 to 5 were prepared by heating and dissolving the components 1 to 9 in the formulation of Table 14 and cooling them with stirring.

Evaluation of Stability of Oily Composition A glass bottle was filled with the oily composition, placed in a constant temperature bath at 40 ° C., and the stability (appearance) after one month was evaluated according to the following criteria.

○: No change ×: Liquid oil separated

Examples 1 to 5 in which dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, and 1,2-octanediol, which are divalent alcohols, were blended at 40 ° C. for one month It was stable with no change.
Comparative Example 2 in which dihydric alcohol was not blended In Comparative Examples 2 to 5 in which ethanol, glycerin, polyethylene glycol, glucose, and raffinose were blended instead of dihydric alcohol, liquid oil separated at 40 ° C. for one month.

<Irritation relaxation test of oil-based composition of Example 1 using collagen gel method>

Comparative Example 5
The oily composition of Comparative Example 6 was stabilized by replacing the oil agent of Example 1 (DEG-DA5) with squalane and blending oily thickener dextrin instead of dipropylene glycol. Ingredients 1 to 5 were dissolved by heating and cooled while stirring.

<Irritation relaxation test using collagen gel method>
The irritation mitigating action of the oil compositions of Example 1 and Comparative Example 6 was compared.
1. Test substance The oil compositions of Example 1 and Comparative Example 6 were used as they were or 0.5% by mass and 0.8% by mass of lauric acid reported to be irritating in animals and humans were added to the oil compositions. This was used as a test substance.

2. Test Method 2.1 Preparation of Collagen Gel Prepare a mixture of type I-AC collagen (Koken) aqueous solution, normal human fibroblasts (manufactured by CAMBLEX) in a medium, and an appropriate amount of reconstituted solution with a stirrer. The final concentration of type I-AC collagen (Koken) is 0.1% by mass, the final concentration of normal human fibroblasts (CAMBLEX) is 4.0 × 10 ⁵ cells / mL, and the 6-well culture insert (manufactured by FALCON) is used. 1 mL was added dropwise. The culture medium was DMEM + 10% FBS. The collagen gel was cultured for about 16 hours (12-24 hours).
2.2 Application of test substance to collagen gel On the collagen gel prepared in 2.1, 1 g of 0.5% by mass, 0.8% by mass of lauric acid added and no test substance was added and allowed to be exposed for 24 hours. It was. After exposure for 24 hours, the test substance was removed, and the cell viability by MTTassay was measured and calculated, and the dependence of the cell viability on the sodium lauryl sulfate concentration was examined.

3. Results The results are shown in FIG.

  Even when 0.5% by mass of lauric acid was mixed with the oily composition of Example 1, the cell viability was 62.1%, but the oil agent (DEG-DA5) formulated in Example 1 was replaced with squalane. In addition, when 0.5% by mass of lauric acid was mixed in Comparative Example 6, the cell viability decreased to 7.9%. The remarkable irritation mitigating action of the oily composition of the present invention was confirmed.

Regarding DEG-DA, the survival rate when creams containing no sodium lauryl sulfate were exposed to cells at various concentrations Regarding DEG-DA, the survival rate when cream containing sodium lauryl sulfate at a concentration of 0.1% was exposed to cells at various concentrations For DEG-DA, the sum of subjects who scored 3 and 4 in the 24-hour evaluation For DEG-DA, the total number of subjects who showed a score of 3 or 4 in the 48-hour judgment For DEG-DA, average transepidermal water transpiration after 24 h (average ± S.D.) About DEG-DA, transepidermal moisture transpiration average after 48 hours after application (average ± S.D.) Cell viability test results for Example 1

Claims (8)

  Oily composition containing dimer dilinoleic acid diethylene glycol oligomer ester and dihydric alcohol.   The divalent alcohol is one or more of dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, and propylene glycol. The oily composition according to claim 1.   Dimerlinoleic acid diethylene glycol oligomer ester is composed of dimerlinoleic acid and diethylene glycol in a ratio of dimerlinoleic acid: diethylene glycol = 0.5 mol: 1.0 mol to 0.8 mol: 1.0 mol. The oil-based composition of Claim 1 or 2 characterized by these.   The dimerdilinoleic acid diethylene glycol oligomer ester has a ratio of dimerdilinoleic acid and diethylene glycol constituting dimerlinoleic acid: diethylene glycol = 0.5 mol: 1.0 mol, according to claim 1 or 2. Oily composition.   The oily composition according to claim 1 or 2, wherein the dimerimlinoleic acid diethylene glycol oligomer ester has a viscosity at 25 ° C of 2,500 to 4,500 mPa · s.   The oil-based composition according to any one of claims 1 to 5, wherein dimer dilinoleic acid diethylene glycol oligomer ester is a skin irritation reducing component.   The oily composition according to any one of claims 1 to 6, which is a facial or body moisturizing cosmetic or a skin external preparation. A skin irritation alleviating cosmetic comprising the oily composition according to claim 7.

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