JPH026729B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to water-in-oil (W/O) emulsions, and more particularly to water-in-oil emulsions containing α-monoglyceryl ether and specific cholesteryl esters, and which are particularly suitable for the protection or treatment of dry skin. Women's skin is especially susceptible to cracks, redness, and rough skin due to outdoor air conditions in winter, washing chinaware, and household chores, and is known to worsen housewife's eczema and progressive palmar keratoderma. There is. Although various creams and ointments have been developed and put on the market to improve and treat such dry skin diseases, it is difficult to find any cream or ointment that is particularly effective. It is almost an established theory that the main causes of dry skin symptoms are a decrease in skin surface lipids and a decrease in moisture within the stratum corneum. This suggests that cream bases that can suppress water evaporation from the skin surface, that is, have water-occlusive properties, are highly effective in alleviating and curing skin dryness symptoms. Vaseline for this purpose,
Lanolin and other oils are often used as oil ingredients, but although they have a high water-occluding effect, they tend not to be liked because they have a sticky feel. Results have shown that creams that are silky, spread well, blend well with the skin, and are smooth are best (Journal of the Japan Cosmetic Engineers Association, 6)
(2)21-27 (1970)). In addition, oil-in-water (O/W) creams have the disadvantage that the use of hydrophilic emulsifiers reduces the water occlusion effect, and that the therapeutic effects of cream bases are naturally lower due to poor water repellency. . The present inventors conducted intensive research to obtain a water-in-oil emulsion that has a high skin surface water evaporation suppressing effect, that is, a water occlusion effect that enhances the therapeutic effect of skin diseases accompanied by dryness symptoms, and is less sticky. The present invention was completed based on the discovery that this object could be achieved by using a specific branched fatty acid cholesteryl ester in combination with a specific branched fatty acid cholesteryl ester. That is, the present invention has the following formula: [In the formula, R is the following formula () (In the formula, m is an integer of 2 to 14, n is an integer of 3 to 11, and the sum of m and n is 9 to 21.) Monoglyceryl ether and formula (); (wherein R' is a saturated aliphatic hydrocarbon group having a total of 11 to 23 carbon atoms and having at least one alkyl substituent from the carboxyl bond position to the center of the main chain) A water-in-oil emulsion characterized by containing a branched fatty acid cholesteryl ester is provided. Monoglyceryl ether having a monomethyl branched alkyl group represented by the formula () is obtained, for example, as a by-product during dimer production of unsaturated acids such as oleic acid (for example, J.Amer.Oil Chem.Soc.
51, 522 (1974)) The carboxylic acid having the above formula is reduced to an alcohol, which can be derived from this (Japanese Patent Application No. 113,188/1988). Among the α-monoglyceryl ethers represented by formula (), those having a branched alkyl group, particularly those having a monomethyl branched alkyl group represented by formula (), are suitable for the purpose of the present invention. The branched fatty acid cholesteryl ester used in the present invention is represented by the following formula (). (In the formula, R′ is a saturated aliphatic hydrocarbon group having a total of 11 to 23 carbon atoms and having at least one alkyl substituent from the carboxyl bond position to the center of the main chain) Branches of the present invention Branched fatty acids (R′COOH) used in the production of fatty acid cholesteryl esters have 12 to 24 carbon atoms (11 to 24 carbon atoms as R′).
23) can be used, but those having 14 to 20 carbon atoms (13 to 19 carbon atoms as R') are preferable. A branched fatty acid is a saturated branched fatty acid having at least one alkyl substituent from the carboxyl group bonding position to the center of the main chain. Such saturated branched fatty acids can be easily obtained from petrochemical raw materials or oleochemical raw materials. An example of such a branched fatty acid obtained from petrochemical raw materials is a branched fatty acid having a side chain at the α position, which is represented by the following formula (). (In the formula, R ₁ and R ₂ are each a linear or branched saturated aliphatic hydrocarbon group, and the sum of the number of carbon atoms of R ₁ and R ₂ is 12 to 18.) In the above formula () The branched fatty acid having a side chain at the α-position can be obtained by, for example, aldol condensation of a linear or branched aldehyde having 7 to 10 carbon atoms.
It can be produced by forming a branched unsaturated aldehyde and then hydrogenating and oxidizing this to form a branched saturated fatty acid. The most easily available branched saturated fatty acid produced by this method is a branched aldehyde having 9 carbon atoms through the oxo reaction of an isobutylene dimer, and then a branched unsaturated aldehyde having 18 carbon atoms by aldol condensation of this aldehyde. Next, a branched fatty acid having 18 carbon atoms, 5,7,7-trimethyl-2, obtained by hydrogenation and oxidation.
-(1,3,3-trimethylbutyl)-octanoic acid (commercially available, for example, from Nissan Chemical Co., Ltd.). The branched fatty acid having a side chain at the α-position represented by the above formula can also be converted into a β-branched alcohol by Guerbet reaction of a linear or branched primary alcohol having 7 to 10 carbon atoms, and then oxidized. It can be obtained by The most readily available branched saturated fatty acids that can be produced by this method are those obtained by the Guerbet reaction of nonyl alcohol followed by an oxidation reaction.
-heptylundecanoic acid (commercially available, for example, from Mitsubishi Kasei Corporation). The branched fatty acid having a side chain at the α-position represented by the above formula () may be produced by any of the methods described above, or may be produced by any other method (for example, an olefin having 13 to 19 carbon atoms). It can be used in the present invention regardless of the method (such as a method in which an aldehyde having a side chain at the α-position is formed by an oxo reaction of Preferred specific examples of saturated branched fatty acids having a side chain at the α-position include the above-mentioned 5,7,7-trimethyl-2-(1,3,3-trimethylbutyl)-octanoic acid and 2-hebutylundecanoic acid. In addition, 2-hexyldecanoic acid, 2-octyldodecanoic acid, 2-
Examples include pentylnonanoic acid. An example of a saturated branched fatty acid obtained from oleochemical raw materials is a fatty acid having a methyl branched chain represented by the following formula (). (In the formula, the sum of m' and n' is 14, and the distribution is centered around m' = n' = 7.) Such methyl branched chain fatty acids are obtained, for example, as a by-product during the production of oleic acid dimer. (e.g., J. Amer. Oil Chem. Soc.., 51 ,
522 (1974)), herein referred to as methyl branched isostearic acid. Methyl branched isostearic acid is commercially available, for example as its isopropyl ester (eg Emery, USA). The branched fatty acid cholesteryl ester of the present invention is
It is produced by a conventional method for producing esters from the above-mentioned branched fatty acids or derivatives thereof and cholesterol. A fatty acid and cholesterol can be reacted as they are to esterify them, or either one can be converted into a more reactive derivative (for example, an acid halide) and then esterified. These branched fatty acid cholesteryl esters are new substances, and a patent application has already been filed for them (patent application filed in 1983).
139788). The water-in-oil emulsion of the present invention contains 0.1 to 10.0 wt.%, preferably 0.5 to 5.0 wt.%, of α-monoglyceryl ether represented by the formula (), and branched cholesteryl ester represented by the formula (). It is appropriate to blend 0.5 to 25.0 wt.%, preferably 2 to 15 wt.%. In preparing the water-in-oil emulsion of the present invention, in addition to the above-mentioned essential ingredients, petrolatum, lanolin, liquid paraffin, natural oils, higher fatty acid alkyl esters, higher fatty alcohols, higher fatty acids, and squalane are used as oil components. etc. can be added in an amount of 1 to 80 wt.%. Since α-monoglyceryl ether itself is an emulsifier, it does not require any other emulsifier, but lecithin, sorbitan fatty acid ester, fatty acid monoglyceride, fatty acid metal salt, magnesium sulfate, etc. may be used as an emulsifier or emulsion stabilizer.
0.5-20wt.% can be added. The remainder is mainly water. Although the water-in-oil emulsion of the present invention can be used for various purposes, it is particularly suitable for use in skin external drug bases, skin cosmetics, and the like. When used as an external skin base, 0.001 to 30 wt.% of drugs such as anti-inflammatory agents, bactericidal agents, anti-allergic agents, vitamins, and moisturizers are usually added. Further, when used as a skin cosmetic, fragrances and the like are further added. According to the present invention, by combining α-monoglyceryl ether and branched fatty acid cholesteryl ester, the water evaporation suppressing effect, that is, the water occlusion effect is enhanced, and at the same time, the stickiness is reduced without reducing this water occlusion effect. . The present invention will be explained below using examples. In addition, a method for producing a new substance used in the Examples is shown as a reference example. Reference Example 1 4770 g of isostearate isopropyl ester (Emery 2310 isopropyl isostearate, commercially available from Emery Company, USA) and 239 g of a copper chromium catalyst (manufactured by JGC) are placed in a 20-meter autoclave. Next, 150Kg/
Fill with hydrogen gas at a pressure of cm ² and then heat the reaction mixture to 275°C. 150Kg/ ^cm2 /
After hydrogenation at 275°C for about 7 hours, the reaction product was cooled and the catalyst residue was removed by filtration to obtain the crude product.
Obtained 3500g. The crude product was distilled under reduced pressure to obtain 3300 g of colorless and transparent isostearyl alcohol as a fraction of 80 to 167°C/0.6 mmHg. The obtained isostearyl alcohol (methyl branched isostearyl alcohol) had an acid value of 0.05, a saponification value of 5.5, and a hydroxyl value of 181.4. It showed absorption at 3340 and 1055 cm ^-1 in IR (liquid film) and at δ3.50 (broad triplet, -CH ₂ -OH) in NMR (CCl ₄ solvent). As for the main component of this alcohol, approximately 75% has an alkyl group with a total carbon number of 18 (the sum of m and n in the formula is 15), and the remaining components have a total carbon number of 14, It was found that all of the branched methyl groups were a mixture of those located near the center of the alkyl main chain. Reference Example 2 (i) 2444 g of isostearyl alcohol obtained in Reference Example 1 was charged into a reaction vessel with a capacity of 5 equipped with a thermometer, a reflux condenser, a dropping funnel, a nitrogen gas inlet tube, and a stirrer. While stirring, thionyl chloride was added dropwise from a dropping funnel at room temperature under nitrogen gas flow. The reaction mixture exothermed and evolved gas at the same time. The temperature of the reaction mixture rose to 31°C at the beginning of the reaction, but gradually decreased to around 18°C as the amount of thionyl chloride added increased. At this point, the reaction mixture was heated to about 40° C., and thionyl chloride was continued to be added dropwise. After gas evolution has subsided, the reaction mixture is
When the temperature was raised to 70 to 80°C, gas generation became intense again, so thionyl chloride was successively added dropwise. The dropping of thionyl chloride was stopped when no gas was observed to be generated at all. The total amount of thionyl chloride added dropwise was 2200 g. The reaction product was cooled, and stirring was continued for about 1 hour at 70-80°C. The reaction product was cooled, and the low-boiling fraction (mainly unreacted thionyl chloride) was distilled off at 40 to 50° C. under normal pressure. The residue was ice-cooled, and ice cubes were added little by little while stirring. After confirming that the intense gas generation had stopped, ether was added, then water was added, and the mixture was thoroughly stirred. The ether layer was separated, neutralized with sodium bicarbonate, the solvent was distilled off, and then distilled under reduced pressure to obtain 2217 g of isostearyl chloride from the fraction at 103-163°C/0.1-1.0 mmHg. IR (liquid film): 725, 650 cm ^-1 NMR (CCl ₄ ): δ 3.50 (triplet line - CH ₂ Cl) (ii) Capacity 5 with thermometer, stirrer, addition funnel and Dean Stark trap. 798 g of isopropylidene glycerol, 1500 ml of xylene, 340 g of 93% sodium hydroxide, and 300 g of water were placed in a reaction vessel, and heated to 130-140°C while stirring.
The mixture was heated to reflux. Water was separated from the distilled water/xylene mixture in a Dean Stark trap and removed from the reaction system, and xylene was returned to the reaction system. After heating under reflux for about 16 hours, when no more water was observed to be distilled out, about 777 g of isostearyl chloride produced in (i) was added to the dropping funnel.
It took 30 minutes to drip. After the dropwise addition was completed, the reaction mixture was further heated under reflux at 130 to 140° C. for about 9 hours to complete the reaction. After cooling, the sodium chloride precipitated in the reactor was removed by filtration, the solvent was distilled off under reduced pressure, and then 176-206℃/0.25-0.50mmHg
800g of fraction was obtained. This is 2,3-O-isopropylidene-1-O-isostearyl glyceryl ether. IR (liquid film): cm ^-1 1200-1260, 1050-1120 (C-O stretching vibration) NMR (CCl ₄ ): δ3.1-4.2 (multiplet,

[Formula]) (iii) Capacity 5 equipped with stirrer, thermometer and reflux condenser
1,103 g of isopropylidene isostearyl glyceryl ether obtained in step (ii) was placed in a reaction vessel, and 1,500 ml of ethanol and 2,000 ml of 0.1N sulfuric acid were added thereto. 80 while stirring the mixture
The mixture was heated to reflux at ~85°C, and after about 10 hours, it was observed by gas chromatography that the isopropylidene isostearyl glyceryl ether was completely hydrolyzed. After cooling, the mixture was allowed to stand still and separated into an oil layer and an aqueous layer. The aqueous layer was extracted with ether, combined with the previous oil layer, and sodium bicarbonate solution was added to neutralize the remaining acid. After separating the organic layer, the solvent was distilled off under reduced pressure,
Further, it was dried by heating at 100°C/0.1mmHg for 3 hours.
900 g of α-mono(isostearyl)glyceryl ether as a colorless transparent liquid was obtained. IR (liquid film): 3400, 1050~1140cm ^-1 NMR ( _CCl4 ): δ3.2~3.8 (multiplet,

[Formula]) Acid value: 0.08, saponification value: 0.36, hydroxyl value:
313.8, iodine value: 0.32 Reference example 3 In a reaction vessel with a capacity of 3 equipped with a thermometer, reflux condenser, dropping funnel, and stirrer, isostearic acid (a methyl branched fatty acid represented by the formula
568 g (2.0 mol) of Emery 875 isostearic acid (commercially available as Emery 875 isostearic acid) was charged. While stirring, 520 g (4.4 mol) of thionyl chloride was added dropwise from a dropping funnel at room temperature under nitrogen gas flow. As the dropwise addition of thionyl chloride progressed, the reaction mixture changed from colorless to pale yellow to black, and at the same time, gas evolution was observed. During the dropwise addition of thionyl chloride,
The temperature of the reaction mixture was kept at room temperature. After adding thionyl chloride dropwise over a period of about 3 hours, the reaction mixture was kept at 60-70°C in an oil bath for about 3 hours. After confirming that gas generation was almost no longer observed, low-boiling substances were distilled off under reduced pressure, and then 153
~170℃/1.0~3.0mmHg fraction 454g (yield 75%)
I got it. This was methyl branched isostearic acid chloride. IR spectrum (liquid film method) 2950, 2920, 2850, 1800 (C=O stretching), 1460,
1400, 1380, 950, 720, 680, 590 cm ^-1 H ¹ -NMR spectrum (CCl ₄ ): δ 0.6-1.0 (m, CH ₃ CH ₂ - and

[Formula] 1.0 to 1.5 (m, -CH ₂ -) 1.5 to 2.0 (m,

[Formula]) 2.77 (t, -C H ₂ COCl) Reference Example 4 281 g of cholesterol was placed in reaction vessel 3 equipped with a thermometer, dropping funnel, reflux condenser, and stirrer.
(0.73 mol), benzene 1500ml, pyridine 100g
(1.27 mol) were added in this order. While stirring the reaction mixture, 212 g (0.70 mol) of methyl branched isostearic acid chloride obtained in Reference Example 3 was added dropwise through a dropping funnel while maintaining the temperature at 25 to 30° C. under nitrogen gas flow. After the dropwise addition is complete, the temperature of the reaction mixture is reduced to approximately 50°C.
It was kept at 70-80°C for about 3 hours, and then kept at 70-80°C for about 8 hours. Through this heat treatment, the esterification reaction proceeded to completion, and it was confirmed by IR spectrum that no acid chloride was contained in the reaction mixture.
The white precipitate of pyridine hydrochloride in the reaction product was removed by filtration, and the resulting filtrate was subjected to solvent distillation under reduced pressure. After mixing in benzene (1000 ml) and dilute hydrochloric acid (1000 ml) and stirring vigorously, the benzene layer was collected by liquid separation. After drying the benzene layer by adding anhydrous sodium sulfate, the benzene was distilled off under reduced pressure to obtain a pale yellow viscous liquid methyl branched isostearic acid cholesteryl ester 460.
g (yield 94%) was obtained. IR spectrum (liquid film) 2950, 2920, 2850, 1730 (C=O stretching), 1460,
1370, 1160, 1000 cm ^-1 H ¹ -NMR spectrum (CCl ₄ solvent): δ 0.70 (s, 3H, steroid skeleton C-18 methyl group) 0.80 (d, 6H, steroid skeleton side chain C-26, C
-27 methyl group) 1.00 (s, 3H, steroid skeleton C-19 methyl group) 0.80 to 1.0 (m, 6H, branched fatty acid CH ₃ CH ₂ - and

[Formula]) 1.0 ~ 2.0 (m) 2.2 (t, 2H, -CH ₂ -CH ₂ -COO-) 4.4 (m, 1H,

[Formula]) 5.25 (m, 1H, steroid skeleton, C-6 olefin proton) Acid value 0.8 (calculated value 0) Saponification value 84.8 (calculated value 86.0) Hydroxyl value 0.7 (calculated value 0) Iodine value 41.4 (calculated value 39.0) Experimental example 1 In vitro water occlusion effect was measured using the cup test method (J.Soc.Cosmet,
Chem. Japan, 13(2), 14-19 (1979)). (Method) Place paper (Kiriyama Roto paper, No. 4 40 mm diameter) over the mouth of a 50 ml glass bottle and secure the paper with a cap cut out to a certain area. Soak the paper in the test cream in advance. Fill a glass bottle with a certain amount of water and leave it under certain conditions (20°C, 50% relative humidity) for 24 hours. The amount of permeated water was determined from the change in weight before and after standing, and was divided by the amount of water permeated through the untreated paper to obtain the water permeation rate (%). The amount of the test cream adhered to the paper was calculated by converting it into 100 mg. (Test cream formulation) Prescription A W/O type cream (product of the present invention) Branched fatty acid cholesteryl ester (produced in Reference Example 4) 10wt.% α-mono(methyl branched alkyl) glyceryl ether (produced in Reference Example 2) 2 Vaseline 5 Lanolin 5 Sulfuric paraffin 5 Isopropyl myristate 5 Purified water 68 Prescription B W/O cream (target) α-mono(methyl branched alkyl) glyceryl ether (in reference example 2) 2wt.% Vaseline 15 Lanolin 5 Liquid paraffin 5 Isopropyl myristate 5 Purified water 68 Prescription C O/W cream (target) Branched fatty acid cholesteryl ester (manufactured in Reference Example 4) 10wt .% Vaseline 5 Lanolin 5 Liquid paraffin 5 Isopropyl myristate 5 Stearic acid monoglyceride 2 Sorbitan monostearate 3 Polyoxyethylene sorbitan monostearate 3 Purified water 62 Commercial product A O/W cream (targeted) ) (Main ingredient only, details unknown) Solid paraffin Hexadecyl-2-ethylhexanoate Olive oil Stearic acid monoglyceride polyoxyethylene sorbitan monostearate Purified water Commercial product B W/O cream (Target) (Main ingredient only, details Unknown) Liquid paraffin Vaseline Lanolin alcohol Aluminum stearate Purified water (results)

[Table] Experimental example 2 In vivo water occlusion effect was measured using the skin-insensitive excretion measurement method, which is commonly used in humans (Journal of the Japanese Dermatological Association 86(12), 815
~823 (Sho 51)). (Method) Place a cup on a designated area on the flexor side of a woman's forearm, pour a mixture of ether (1) and acetone (1), and apply the cup twice for 30 seconds to degrease. Rest for 20 minutes in a variable environment room set at constant conditions (20°C, 50% relative humidity).
Measure the amount of insensible excretion at each site. radius 20cm
(12.56 cm ² ), apply a certain amount of the test cream, and measure the amount of insensible excretion 30 and 60 minutes after application. The occlusion rate is determined by the following formula. (Insensible metabolic rate before cream application) - (Insensible metabolic rate after cream application) / (Insensible metabolic rate before cream application) x 100 To measure the insensible metabolic rate, use an Evapori meter and apply it to the skin. The value was read 1 minute after contact. (Result)

[Table] Experimental Example 3 Evaluation of stickiness of cream by tube function evaluation (method) A certain amount of the test cream was applied to the backs of the hands of 20 female panelists, and the stickiness was evaluated. (Result)

[Table] From the results of Experimental Examples 1 and 2, W/O of formulation A according to the present invention containing α-monoglyceryl ether and branched fatty acid cholesteryl ester
It can be seen that the W/O type cream of Formulation B, which contains Vaseline in place of the branched fatty acid cholesteryl ester, has an excellent water occlusion effect (that is, an effect of suppressing water evaporation from the skin surface). On the other hand, from the results of Experimental Example 3, it was found that the W/O type cream of Prescription A was different from the W/O type cream of Prescription B.
It can be seen that it is less sticky than O type cream. Examples of the W/O type cream of the present invention are shown below. Branched fatty acid cholesteryl ester used,
α-Monoglyceryl ether was produced in Reference Example. Example 1 [1] Branched fatty acid cholesteryl ester 10.0wt.% [2] Vaseline 5.0 [3] Lanolin 5.0 [4] Liquid paraffin 5.0 [5] α-monoglyceryl ether 2.0 [6] Ste. Aluminum phosphate 0.05 [7] Sodium benzoate 0.3 [8] Purified water The remainder [1] to [6] were mixed and heated to 60°C. 60℃
While adding the heated mixture of [7] and [8], the mixture was stirred and emulsified. The emulsion was cooled to room temperature to obtain a W/O type cream. Example 2 W/O type cream containing anti-inflammatory agent Branched fatty acid cholesteryl ester 5.0% Vaseline 5.0 Squalane 5.0 Liquid paraffin 5.0 2-ethylhexyl adipate 5.0 Propyl parahydroxybenzoate 0.1 Lecithin 0.5 Sorbitan sesquioleate 2.0 Aluminum monostearate 0.05 α-mono Glyceryl ether 2.0% Allantoin 1.5 Methyl para-hydroxybenzoate 0.1 Magnesium sulfate 0.5 Purified water Remaining amount example 3 W/O type cream containing bactericide Branched fatty acid cholesteryl ester 10.0% Vaseline 5.0 Lanolin 5.0 Liquid paraffin 5.0 Isopropyl myristate 5.0 Para-hydroxybenzoin Propyl acid 0.1 Aluminum monostearate 0.05 α-monoglyceryl ether 2.0 Methyl para-hydroxybenzoate 0.1 Chlorhexidine gluconate (20%) 0.5 Purified water Remaining amount example 4 W/O type cream containing vitamins Branched fatty acid cholesteryl ester 5.0% Salad Beeswax 3.0 Squalane 2.0 Liquid paraffin 5.0 2-ethylhexyl adipate 5.0 Propyl para-hydroxybenzoate 0.1 Aluminum monostearate 0.05 α-monoglyceryl ether 2.0 dl-α-tocopherol acetate 0.2 Methyl para-hydroxybenzoate 0.1 Purified water Remaining amount example 5 Moisturizing agent-containing W/O type cream Branched fatty acid cholesteryl ester 10.0% Vaseline 5.0 Squalane 5.0 Liquid paraffin 5.0 2-ethylhexyl adipate 5.0 Aluminum monostearate 0.05 α-monoglyceryl ether 2.0% Propyl para-hydroxybenzoate 0.1 Methyl para-hydroxybenzoate 0.1 Magnesium sulfate 0.5 Urea 5.0 Purified water remaining amount

Claims (1)

[Claims] 1 Formula (); [In the formula, R is the following formula () (In the formula, m is an integer of 2 to 14, n is an integer of 3 to 11, and the sum of m and n is 9 to 21.) Monoglyceryl ether and formula (); (wherein R' is a saturated aliphatic hydrocarbon group having a total of 11 to 23 carbon atoms and having at least one alkyl substituent from the carboxyl bond position to the center of the main chain) A water-in-oil emulsion characterized by containing branched fatty acid cholesteryl ester.