JP4817435B2 - Topical skin preparation - Google Patents

Description

  The present invention relates to an emulsion-type external preparation for skin, which contains an amphiphilic compound and has high stability and good usability.

  Emulsion-type skin care cosmetics have been widely used since they can give appropriate oil and moisture to the skin and the like. However, an emulsion (emulsified liquid) is a thermodynamically unstable system, and eventually it is separated into two phases through processes such as creaming, aggregation and coalescence. For this reason, various stabilization techniques have been used in the production process of emulsion-type cosmetics. Among these stabilization techniques, the emulsification technique is extremely important.

  Examples of emulsification techniques used to stabilize emulsions include: phase inversion emulsification method, HLB temperature emulsification method, D phase emulsification method, etc., preparation method by surface chemistry method, coagulation method, fine emulsion preparation method, high pressure emulsifier There are a fine emulsion preparation method by SPG, an SPG membrane emulsification method, an emulsion preparation method using a surfactant-higher alcohol aggregate, a liquid crystal emulsification method, a W / O emulsification method using amino acids, etc. (Non-patent Document 1) .

Recently, emulsion-type cosmetics using water-in-oil emulsion compositions that can be expected to have a high moisturizing effect due to the blocking effect of the oil phase as a continuous phase are promising. Often applied to creams. However, water-in-oil emulsified cosmetics generally tend to have a strong stickiness. Accordingly, cosmetics have been developed in which a silicone oil having a less sticky feeling is used as an oil component, and a high internal water phase is obtained using a cross-linked polyether-modified silicone as an emulsifier (see Patent Documents 1 to 3). However, a product containing a large amount of silicone oil is certainly less sticky, but has a problem of insufficient moisturizing effect (moist feeling). In order to prepare a water-in-oil emulsified cosmetic with sufficient moisturizing effect (moist feeling) and less stickiness, an appropriate amount of hydrocarbon oil is blended as an oil component, and a large amount of water is stably emulsified. It is possible to make it. However, in the case of a water-in-oil emulsion containing an appropriate amount of hydrocarbon oil as an oil component, a stable emulsion cannot be obtained by using a silicone-based amphiphilic compound such as a crosslinked polyether-modified silicone as an emulsifier. . As an emulsifier in such a case, it is conceivable to use a lipophilic hydrocarbon-based amphiphilic compound as an emulsifier, but a hydrocarbon-based parent having a long-chain fatty acid residue or a higher alcohol residue as a lipophilic group. In general, amphiphilic compounds have a high Kraft point (T _K ; Krafft eutectic temperature), so that the resulting emulsion has poor stability, particularly low temperature stability. is doing.

  Amphiphilic compounds form various liquid crystal structures (hexagonal liquid crystals, reverse hexagonal liquid crystals, lamellar liquid crystals, cubic liquid crystals, etc.) in water at temperatures above the Kraft point. Using this liquid crystal forming ability, various amphiphilic compounds (surfactants) are blended in cosmetics to improve stability and impart moisturizing properties (see Patent Documents 4 and 5). Conventional cosmetics using these liquid crystal systems still have problems in terms of long-term stability and oil content. In addition, for example, an amphiphilic compound having a long-chain fatty acid residue or a higher alcohol residue as a lipophilic group generally has a high Kraft point, and therefore cannot form a stable liquid crystal structure at low temperatures. Often not suitable for storage. Therefore, the present inventors previously produced a glycolipid having an isoprenoid chain with a relatively low Kraft point (Patent Document 6), but has a Kraft point lower than the refrigeration temperature for use in cosmetics and the like. The use of amphiphilic compounds may be preferred.

JP 2001-2521 A JP 2001-139449 A Japanese Laid-Open Patent Publication No. 2004-307371 Japanese Patent No. 3074313 Japanese Patent No. 2946145 JP 2002-226497 A Fragrance Journal, Editorial Department, “Cosmetic Manufacturing Studies -Technology and Practice”, Fragrance Journal, 2001, p. 1-16

  An object of the present invention is to provide a skin external preparation having high stability and good usability.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that an alcohol residue or fatty acid residue having a lipophilic group represented by the following general formula (1) or (2) as an isoprenoid chain and OH Various emulsified compositions (O / W type, W / O type, O / W / O type, etc.) containing an amphiphilic compound composed of a hydrophilic group having three or more groups and an oil were prepared. The water-in-oil emulsified composition obtained by emulsifying an aqueous medium to which an amphiphilic compound and an oil are added is found to have high stability and a good feeling when used on the skin. It came to do. The production of some amphiphilic compounds that can be used particularly preferably in the external preparation for skin of the present invention is also disclosed in International Application No. PCT / JP2005 / 019639.

That is, the present invention includes the following.
[1] A skin external preparation comprising a water-in-oil emulsion composition comprising at least one amphiphilic compound represented by the following general formula (1) or (2) and an oil, The skin external preparation whose content in the said composition is 0.1-20 mass%.

(In the formula, n and n ′ represent an integer of 0 to 4, m and m ′ represent an integer of 0 to 3, and R and R ′ represent a hydrophilic group having three or more hydroxyl groups)
[2] The skin according to [1], wherein R and R ′ are residues obtained by removing one hydroxyl group from any one selected from the group consisting of erythritol, pentaerythritol, xylose, and ascorbic acid. Topical agent.
[3] The skin external preparation of [1] or [2], wherein the amphiphilic compound has a Kraft point of less than 6 ° C.
[4] The above [1] to [3], wherein the oil component is at least one selected from the group consisting of silicone oil, ester oil, hydrocarbon oil, oil and fat, and waxes, and includes at least hydrocarbon oil Topical skin preparation.
[5] The external preparation for skin according to the above [1] to [4], further comprising a physiologically active substance.

  The external preparation for skin of the present invention has high stability and can give a good feeling of use.

  Hereinafter, the present invention will be described in detail.

  The present invention relates to a skin external preparation containing at least one amphiphilic compound represented by the above general formula (1) or (2). Preferably, the external preparation for skin of the present invention is a water-in-oil emulsion composition comprising at least one amphiphilic compound represented by the above general formula (1) or (2) and an oil. The water-in-oil emulsion composition is a composition in which water or an aqueous solution is dispersed as fine particles in an oil phase, and is generally referred to as a W / O emulsion or the like.

  In the present invention, the above amphiphilic compound is blended with an oil and emulsified, so that, for example, even when a large amount of water is blended with a hydrocarbon oil as a main oil, a high internal phase ratio water-in-oil emulsion composition is obtained. Can be prepared. Further, the external preparation for skin of the present invention can maintain high stability over a long period of time even if it is prepared as a cosmetic containing a relatively large amount of oil such as a cosmetic cream or milky lotion. The feeling of use is also good, such as being less.

  The amphiphilic compound to be blended in the external preparation for skin of the present invention may be any compound represented by the above general formula (1) or (2). In this amphiphilic compound, a hydrophilic group (in the above general formula (1) or (2), represented by R or R ′ and having three or more hydroxyl groups) is erythritol, pentaerythritol, threitol, diglycerol. It is preferably a residue obtained by removing one hydroxyl group from xylose, ribose, arabinose, lyxose, ascorbic acid, glucose, galactose, mannose, fructose, altrose, gulose, idose, talose, triglycerol, etc., erythritol, penta More preferably, it is a residue obtained by removing one hydroxyl group from erythritol, xylose, or ascorbic acid. Moreover, it is more preferable that the amphiphilic compound represented by the general formula (1) or (2) to be blended in the external preparation for skin of the present invention has a Kraft point of less than 6 ° C.

  Examples of amphiphilic compounds that are particularly preferably used in the present invention include compounds represented by the following formulas (3) to (15).

  The synthesis of these compounds of formulas (3) to (15) is described in detail in the examples below. In addition, for those amphiphilic compounds of the present invention other than the compounds of formulas (3) to (15), those skilled in the art will use well-known organic chemical synthesis methods and biochemical production methods based on the examples described below. And can be easily manufactured.

  The content of the amphiphilic compound in the external preparation for skin of the present invention is usually 0.1 to 20% by mass, preferably 0.5 to the total amount of the water-in-oil emulsion composition constituting the external preparation for skin. 10% by mass. For example, an emulsion obtained by adding one or more amphiphilic compounds to an aqueous medium together with an oil in a blending amount corresponding to a final concentration of 0.1 to 20% by mass, and emulsifying it is 0.1 to 20% by weight of amphiphilic compound is included.

  The oil to be blended in the external preparation for skin of the present invention may be any oily raw material usually used in the cosmetics field, and is not limited to, for example, silicone oil, ester oil, hydrocarbon oil, oil and fat, Examples include waxes, higher fatty acids, and higher alcohols. As the oil used in the external preparation for skin of the present invention, it is particularly preferable to use one or more of silicone oil, ester oil, hydrocarbon oil, oil and fat, and waxes. Furthermore, it is preferable that the oil used in the external preparation for skin of the present invention contains at least a hydrocarbon oil. In the skin external preparation of the present invention, an oily raw material mixture containing hydrocarbon oil as a main oil can be suitably used as an oil. The skin external preparation of the present invention contains not only a moisturizing effect and a moist feeling, but also a smooth feel to the skin.

  Suitable silicone oils include, for example, linear polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, methylhydrogenpolysiloxane, decamethylpolysiloxane, dodecamethylpolysiloxane. Examples thereof include cyclic polysiloxanes such as siloxane and tetramethyltetrahydrogenpolysiloxane, silicone resins and silicone rubbers.

  Suitable ester oils include, for example, glyceryl tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, hexyl laurate, isopropyl myristate, octyldodecyl myristate, octyl palmitate, stearic acid Isocetyl, isopropyl isostearate, octyl isopalmitate, isodecyl oleate, diisopropyl adipate, diethyl sebacate, diisostearyl malate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, myristyl myristate, decyl oleate, Hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl isostearate, cholesteryl hydroxystearate, 1 -Cholesteryl hydroxy stearyl, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, tri-2-ethylhexyl acid Trimethylolpropane, trimethylolpropane triisostearate, pentane erythritol tetra-2-ethylhexylate, glycerin tri-2-ethylhexylate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, trimyristin Acid glycerin, tri-2-heptylundecanoic acid glyceride, castor oil fatty acid methyl ester, oleic acid oil, cetostearyl alcohol Cole, acetoglyceride, 2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, di-2 sebacate -Ethylhexyl, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, etc. .

  Suitable hydrocarbon oils include liquid paraffin, ozokerite, squalane, paraffin, isoparaffin, pristane, ceresin, petrolatum, microcrystalline wax and the like. More preferred hydrocarbon oil as the main oil is squalane and / or liquid paraffin.

  Suitable oils and fats include, for example, avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, southern castor oil, castor oil, linseed oil , Safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnagiri oil, Japanese kiri oil, germ oil, triglycerin, trioctanoic acid glycerin, triisopalmitic acid glycerin, etc. A liquid fat is mentioned. Alternatively, suitable fats and oils include, for example, cocoa butter, coconut oil, horse fat, hydrogenated coconut oil, palm oil, beef tallow, sheep fat, hardened beef tallow, palm kernel oil, pork fat, beef bone fat, owl kernel oil, hydrogenated oil Also, solid fats such as beef leg fat, molasses, hydrogenated castor oil are included.

  Suitable waxes include, for example, beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ibota wax, whale wax, montan wax, nuka wax, lanolin, kapok wax, lanolin acetate, liquid lanolin, sugarcane wax, lanolin fatty acid isopropyl, hexyl laurate, Examples include reduced lanolin, jojoba wax, hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, jojoba oil and the like.

  In the external preparation for skin of the present invention, higher alcohols such as behenyl alcohol, batyl alcohol and stearyl alcohol, and higher fatty acids such as stearic acid and palmitic acid can also be used as oils.

  The oil content in the skin external preparation of the present invention is generally 5 to 40% by mass, preferably 8 to 26% by mass, based on the total amount of the water-in-oil emulsion composition constituting the skin external preparation. Preferably it is 8-18 mass%. The oil in the external preparation for skin of the present invention preferably contains a hydrocarbon oil, and the content of the hydrocarbon oil in that case is generally based on the total amount of the water-in-oil emulsion composition constituting the external preparation for skin. Specifically, it is 1 to 20% by mass, preferably 2 to 16% by mass, and more preferably 3 to 8% by mass.

  The skin external preparation of the present invention may be blended with various vitamins and medicinal ingredients which are physiologically active substances often blended in cosmetics and quasi drugs. Examples of such physiologically active substances include vitamin C, vitamin C phosphate ester magnesium, vitamin C stearate ester, vitamin C palmitate ester, vitamin C dipalmitate ester, vitamin C tetraisopalmitate ester, ascorbic acid Whitening agents such as glucose, arbutin, ellagic acid, tranexamic acid, oil-soluble licorice extract, crunchy extract, toki extract, retinol, retinol acetate, retinol palmitate, retinoic acid, hyaluronic acid, astaxanthin, tocotrienol, ubiquinone, aloe, ougone, etc. Anti-aging agents, glycyrrhetinic acid, glycyrrhizic acid, amino acids, sugars, mucopolysaccharides, hydrolyzed proteins, sphingolipids, ceramides, phospholipids and other rough skin inhibitors, tocopherols Tocopherol acetate, SOD, beta-carotene, catechin, an anti-oxidant such as polyphenols, .gamma.-oryzanol, minoxidil, assembly extract, capsicum tincture, benzyl nicotinate, pantothenic acid, biotin, and the like hair growth agents such as estradiol.

  The skin external preparation of the present invention includes stabilizers used in cosmetics and quasi drugs, for example, clay minerals such as bentonite organically modified with a cationic surfactant, amino acids, amino acid salts, polyethylene glycol, sodium sulfate Further, stability may be further improved by blending distearyldimethylammonium hectorite or the like.

  In the external preparation for skin of the present invention, surfactants or emulsifiers other than the above components, diluents, humectants, thickeners, preservatives, neutralizing agents, which are generally blended in cosmetics and quasi drugs, etc. Other components such as a buffer, a dispersant, a water-soluble polyhydric alcohol, a pH adjuster, a chelating agent, an ultraviolet absorber, an ultraviolet scattering agent, a fragrance, a pigment, and a dye may be blended. Those components may be blended one by one or two or more.

  The skin external preparation of the present invention which is a water-in-oil emulsion contains water in addition to the above components. The water content in the external preparation for skin of the present invention is generally 30 to 90% by mass, preferably 40 to 85% by mass, more preferably 60 to 80% by mass, based on the total amount of the water-in-oil emulsion composition. %.

  The skin external preparation of this invention can be prepared as a water-in-oil emulsion composition by emulsifying the liquid mixture containing the said component. The mixture containing the above components may be emulsified by a conventional method using any emulsification technique known to those skilled in the art, but is more preferably emulsified using a mechanical emulsification method. Examples of the mechanical emulsification method include, but are not limited to, mechanical stirring, mechanical shearing, membrane emulsification, or ultrasonic crushing. Such mechanical emulsification includes, for example, a low speed stirrer (propeller type, anchor type, paddle type, etc.), a high speed high shear stirrer (homomixer, disper, ultra mixer, etc.), and a high pressure homogenizer (gorin homogenizer, microfluidizer, etc.). Also, it can be carried out by an emulsifier / disperser such as an ultrasonic emulsifier or a static mixer (static mixer, membrane emulsifier). When the liquid mixture containing the above components is subjected to mechanical emulsification, the liquid mixture is atomized, and as a result, the aqueous phase becomes fine particles and dispersed in the oil phase to produce an emulsified composition. Specifically, for example, an amphiphilic compound according to the present invention, an oil component, water, and other components are mixed to prepare a mixed solution, and then emulsified with an emulsifying disperser, whereby the oil according to the present invention is added. A water-type emulsion composition can be prepared. After preparing the mixed solution, it may be mixed well by stirring or the like before emulsification. Alternatively, an oil phase containing at least an amphiphilic compound and an oil component according to the present invention and an aqueous medium (water phase) composed of water to which a water-soluble component is optionally added are prepared, preferably the oil phase and the water phase. May be mixed and dispersed by stirring under high temperature conditions, and then the oil phase and the aqueous phase may be further mixed to prepare a mixed solution and emulsified. The external preparation for skin of the present invention may contain a plurality of emulsifiers or dispersants to aid emulsification, but for the purpose of reducing the types of additives, emulsifiers or dispersants other than the above amphiphilic compounds (such as surfactants and surfactants). It is preferable not to contain an amphiphilic compound.

  The external preparation for skin of the present invention can be used by being contained in any product intended to be applied to the skin, such as cosmetics, pharmaceuticals, quasi drugs, bathing agents, wiping agents, and the like. As products using the external preparation for skin of the present invention, for example, emulsions, creams, cleansing creams, medicated creams, foundations, eyeliners, mascaras, eye shadows, and the like are particularly preferable.

  The external preparation for skin of the present invention has high stability, and for example, hardly separated even after long-term storage (at least 1 month). Since the external preparation for skin of the present invention is stable without causing separation even when stored under low temperature conditions (for example, a refrigeration temperature of 6 ° C. or lower, preferably 0 ° C. to 4 ° C.), it is stored refrigerated. Suitable for The skin external preparation of the present invention also has a good feeling of use. The external preparation for skin of the present invention stably contains a relatively large amount of oil, so it has a moisturizing effect and a moist feeling, while it is a high internal water phase type that contains a large amount of moisture, and it feels refreshing and less sticky. Bring.

  Hereinafter, the present invention will be described more specifically with reference to examples. However, the technical scope of the present invention is not limited to these examples.

(Synthesis example)
The synthesis example of the amphiphilic compound which can be mix | blended with the skin external preparation of this invention is shown.
Synthesis Example 1: Synthesis of 1-O- (3,7,11-trimethyldodecyl) erythritol [Formula (3)]

  Under a nitrogen atmosphere, 22.8 g (100 mmol) of 3,7,11-trimethyldodecanol and 9.48 g (120 mmol) of pyridine were dried into methylene chloride in a solution of 20.96 g (110 mmol) of p-toluenesulfonyl chloride in 100 ml of dry methylene chloride. The solution dissolved in 200 ml was added dropwise under ice cooling (1-2 ° C.). After the dropwise addition, the mixture was stirred overnight at room temperature, and the resulting reaction solution was washed successively with 200 ml of water, 200 ml of 2N hydrochloric acid and 200 ml of saturated aqueous sodium hydrogen carbonate, and dried over anhydrous magnesium sulfate. After filtration and concentration, 41.6 g of crude 3,7,11-trimethyldodecyl tosylate was obtained.

In a nitrogen atmosphere, 16.0 g (131 mmol) of esitol was dissolved in 400 ml of dry DMF. Under ice-cooling (2-4 ° C.), a solution in which 2.62 g (65.5 mmol as 60%) of 50-70% NaH after removing the oil with hexane was suspended in about 50 ml of DMF was divided into several times. Added. After the addition, after stirring at room temperature for 1 hour, the temperature was raised to about 50 ° C., and 13.1 g (34 mmol) of the crude 3,7,11-trimethyldodecyl tosylate obtained above was dropped, and the amount attached to the dropping device was reduced. The mixture was washed with 55 ml of DMF, heated to 80 ° C., and stirred for 4 hours. The resulting reaction solution was concentrated, 300 ml of dichloromethane and 1,000 ml of saturated brine were added to the residue, and the organic layer was separated. The aqueous layer was extracted with 150 ml of dichloromethane, and 500 ml of the organic layer was washed twice with 300 ml of saturated brine and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated to obtain 7.7 g of a brown oily substance. This was subjected to column purification using 400 g of silica gel [CH ₂ Cl ₂ → CH ₂ Cl ₂ : MeOH (98: 2) → CH ₂ Cl ₂ : MeOH (95: 5)], and 1-O— (3,7 , 11-trimethyldodecyl) erythritol 0.66 g was obtained. The HPLC purity was 100.0%. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (270 MHz, CDCl ₃ , TMS) δ: 0.83-0.9 (m, 12H), 1.0-1.7 (m, 17H), 2.31 (br.s, 1H ), 2.65 (br.s, 1H), 2.77 (br.s, 1H), 3.5-3.7 (m, 4H), 3.7-3.9 (m, 4H)

Synthesis Example 2: Synthesis of 1-O- (5,9,13-trimethyltetradecyl) erythritol [Formula (4)]

  Under a nitrogen atmosphere, a solution of 22.1 g (0.12 mol) of p-toluenesulfonyl chloride in 100 ml of dry methylene chloride was charged with 27 g (0.11 mol) of 5,9,13-trimethyl-1-tetradecanol and 10 g (0. 0.1 mol) of pyridine. 13 mol) in 200 ml of dry methylene chloride was added dropwise under ice cooling. After the dropwise addition, the mixture was stirred overnight at room temperature, and the resulting reaction solution was washed successively with 200 ml of water, 200 ml of 2N hydrochloric acid and 200 ml of saturated aqueous sodium hydrogen carbonate, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 34.4 g of (5,9,13-trimethyltetradecyl) tosylate.

  Under a nitrogen stream, 25.8 g (0.21 mol) of erythritol was dissolved in 200 ml of dry DMF, and 4.2 g (0.11 mol) of 60% NaH was added in several portions while cooling with ice. After the addition, the mixture was stirred at room temperature for 1 hour, heated to 50 ° C., and 17.2 g of a half amount of (5,9,13-trimethyltetradecyl) tosylate obtained above was added dropwise and washed with 55 ml of DMF. After heating to 80 ° C. and stirring for 4 hours, the resulting reaction solution was concentrated under reduced pressure, 500 ml of ether was added to the remaining solution, and the mixture was extracted and dissolved twice, washed twice with saturated brine, and anhydrous sulfuric acid. Dried with magnesium. After filtration, the filtrate was concentrated and purified by silica gel column chromatography to obtain 2.3 g of 1-O- (5,9,13-trimethyltetradecyl) erythritol having the following physical properties. The purity of this product by HPLC analysis was 76.9% 1-O- (5,9,13-trimethyltetradecyl) erythritol, 23.1% 2-O- (5,9,13-trimethyltetradecyl) erythritol. Met. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (270 MHz, CDCl ₃ , TMS) δ: 0.845, 0.867 (d, J = 6.9 Hz, 6.6 Hz, 12H), 1.0-1.6 (m, 21H) , 3.51 (t, J = 7.5 Hz, 2H), 3.55-3.85 (m, 6H)

Synthesis Example 3: Synthesis of 1-O- (3,7,11,15-tetramethylhexadecanoyl) erythritol [1-O- (phytanoyl) erythritol; formula (5)]

  Under a nitrogen atmosphere, 1 drop of pyridine was added to 2.5 g of phytanic acid and 12.5 ml of methylene chloride, and 1.43 g of thionyl chloride was added dropwise at room temperature. After completion of the dropwise addition, the mixture was refluxed for 1 hour and concentrated under reduced pressure to obtain about 2.6 g of phytanic acid chloride.

  Under a nitrogen atmosphere, 1.33 g of erythritol, 1.15 g of pyridine, and 40 ml of dry N, N-dimethylformamide were mixed and dissolved by heating. The solution was cooled to room temperature, a solution of 2.40 g of phytanic acid chloride obtained above in 7 ml of methylene chloride was added dropwise, and the mixture was stirred at room temperature for 1 hour after the addition. 100 ml of methylene chloride was added, washed with 300 ml of saturated brine, then washed twice with 200 ml, and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, 1.4 g of transparent semi-solid 1-O- (3,7,11,15-tetramethylhexadecanoyl) erythritol was obtained by purification by silica gel column chromatography. As a result of HPLC analysis using acetonitrile: water (4: 1) as a carrier solvent and CAPCELLPAK SG-120 (5 μm) as a column, this product was 1-O- (3,7,11,15-tetramethylhexa). Decanoyl) erythritol 91.1% and 2-O- (3,7,11,15-tetramethylhexadecanoyl) erythritol 8.5%. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (270 MHz, CDCl ₃ , TMS) δ: 0.8-0.9 (m, 12H), 0.93 (d, J = 6 Hz, 3H), 1.0-1.6 (m 22H), 1.95 (br.s, 1H), 2.13 (dd, J = 14 Hz, 9 Hz, 1H), 2.37 (dd, J = 14 Hz, 6 Hz, 1H), 3.33 (br .S, 1H), 3.43 (br.s, 1H), 3.58-3.92 (m, 4H), 4.27 (d, J = 5 Hz, 1H)

Synthesis Example 4: Synthesis of mono-O- (3,7,11,15-tetramethylhexadecyl) pentaerythritol [mono-O- (phytanyl) pentaerythritol; formula (6)]

  Under a nitrogen atmosphere, 29.16 g (97.67 mmol) of phytanol and 9.27 g (117.2 mmol) of pyridine are dissolved in 220 ml of dry methylene chloride, and p-toluenesulfonyl chloride is kept under ice cooling so that the liquid temperature does not exceed 10 ° C. 20.48 g (107.4 mmol) was added in small portions. After completion of the addition, the mixture was stirred for 12 hours until phytanol disappeared, and the resulting reaction solution was washed successively with 200 ml of water, 200 ml of 2N hydrochloric acid and 200 ml of saturated aqueous sodium hydrogen carbonate, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 61.31 g of phytanyl tosylate.

  Under a nitrogen stream, 36.09 g (265.1 mmol) of pentaerythritol was dissolved in 210 ml of dry DMF, and 5.3 g (132.5 mmol) of 60% NaH was added little by little while cooling with ice. After warming to room temperature and stirring for 1 hour, 30.0 g (66.26 mmol) of phytanyl tosylate was added dropwise and washed with 55 ml of DMF. After heating to 80 ° C. and stirring for 4 hours, the resulting reaction solution was concentrated under reduced pressure, 500 ml of ether was added to the remaining solution, and the mixture was extracted and dissolved twice, washed twice with saturated brine, and anhydrous sulfuric acid. Dried with magnesium. After filtration, it is concentrated and purified by silica gel column chromatography to obtain 6.3 g of colorless transparent and slightly viscous liquid mono-O- (3,7,11,15-tetramethylhexadecyl) pentaerythritol. It was. The purity of this product by HPLC analysis was 99.5% or more. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (270 MHz, CDCl ₃ , TMS) δ: 0.8-1.7 (m, 39H), 2.68 (br.s, 3H), 3.44 (br, 4H), 3. 69 (br.s, 6H)

Synthesis Example 5: Synthesis of mono-O- (3,7,11,15-tetramethylhexadecanoyl) pentaerythritol [mono-O- (phytanoyl) pentaerythritol; formula (7)]

  Under a nitrogen atmosphere, 1 drop of pyridine was added to 2.0 g of phytanic acid and 10 ml of methylene chloride, and 1.14 g of thionyl chloride was added dropwise at room temperature. After completion of the dropwise addition, the mixture was refluxed for 1 hour and concentrated under reduced pressure to obtain about 2 g of phytanic acid chloride.

  Pentaerythritol (0.88 g), pyridine (0.69 g), and dry 1,3-dimethyl-2-imidazolidinone (25 ml) were mixed and dissolved by heating. After cooling to room temperature, a solution of 1.32 g of the phytanic acid chloride obtained above in 5 ml of methylene chloride was added dropwise, and the mixture was stirred at room temperature for 1 hour after the addition. 100 ml of methylene chloride was added to the resulting reaction solution, washed 5 times with 100 ml of saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. After removing residual dimethylimidazolidinone, the concentrated solution was purified by silica gel column chromatography to obtain transparent semi-solid mono-O- (3,7,11,15-tetramethylhexadecanoyl) pentaerythritol. .64 g was obtained. The purity of this product by HPLC analysis was 99.4%. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (270 MHz, CDCl ₃ , TMS) δ: 0.7-0.9 (m, 12H), 0.95 (d, J = 7 Hz, 3H), 1.0-1.6 (m 22H), 1.9 (br.s, 1H), 2.15 (dd, J = 14 Hz, 9 Hz), 2.38 (dd, J = 14 Hz, 7 Hz, 1H), 3.17 (br.s). , 2H), 3.62 (s, 6H), 4.16 (s, 2H)

Synthesis Example 6 Synthesis of 1-O- (5,9,13,17-tetramethyloctadecanoyl) erythritol [Formula (8)]

  Under a nitrogen atmosphere, one drop of pyridine was added to 10 g of 5,9,13,17-tetramethyloctadecanoic acid and 20 ml of methylene chloride, and 5.2 g of thionyl chloride was added dropwise at room temperature. After completion of the dropwise addition, the mixture was refluxed for 1 hour and concentrated under reduced pressure to obtain 10.5 g of 5,9,13,17-tetramethyloctadecanoic acid chloride.

  2.56 g of erythritol, 2.21 g of pyridine, and 70 ml of dry DMF were mixed and dissolved by heating. After cooling to room temperature, a solution prepared by dissolving 5 g of 5,9,13,17-tetramethyloctadecanoic acid chloride obtained above in 10 ml of methylene chloride was added dropwise, and the mixture was stirred at room temperature for 1 hour after the addition. 100 ml of methylene chloride was added to the resulting reaction solution, washed 3 times with saturated brine, and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, 2.83 g of transparent semi-solid 1-O- (5,9,13,17-tetramethyloctadecanoyl) erythritol was obtained by purification with silica gel column chromatography. The purity of the product by HPLC analysis was 1-O- (5,9,13,17-tetramethyloctadecanoyl) erythritol 91.6%, 2-O- (5,9,13,17-tetramethylocta Decanoyl) erythritol was 8.4%. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (270 MHz, CDCl ₃ , TMS) δ: 0.8-0.9 (m, 15H), 1.0-1.7 (m, 26H), 2.11 (br.s, 1H) ), 2.33 (t, J = 7.9 Hz, 2H), 2.66 (br.s, 1H), 2.75 (br.s, 1H), 3.6-3.9 (m, 4H) ), 4.29-4.36 (m, 2H)

Synthesis Example 7: Synthesis of mono-O- (5,9,13,17-tetramethyloctadecyl) pentaerythritol [formula (9)]

  Under a nitrogen atmosphere, 30 g (0.09 mol) of 5,9,13,17-tetramethyl-1-octadecanol and pyridine 8 were added to a solution of 19.3 g (0.10 mol) of p-toluenesulfonyl chloride in 100 ml of dry methylene chloride. A solution of 72 g (0.11 mol) dissolved in 200 ml of dry methylene chloride was added dropwise under ice cooling. After the dropwise addition, the mixture was stirred overnight at room temperature, and the resulting reaction solution was washed successively with 200 ml of water, 200 ml of 2N hydrochloric acid and 200 ml of saturated aqueous sodium hydrogen carbonate, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 42 g of (5,9,13,17-tetramethyloctadecyl) tosylate.

  Under a nitrogen stream, 25 g (0.18 mol) of pentaerythritol was dissolved in 200 ml of dry DMF, and 3.7 g (0.09 mol) of 60% NaH was added in several portions while cooling with ice. After the addition, the mixture was stirred at room temperature for 1 hour and then heated to 50 ° C., and 21 g of the above-obtained (5,9,13,17-tetramethyloctadecyl) tosylate was added dropwise and washed with 55 ml of DMF. After heating to 80 ° C. and stirring for 4 hours, the resulting reaction solution was concentrated under reduced pressure, 500 ml of ether was added to the remaining solution, and the mixture was extracted and dissolved twice, washed twice with saturated brine, and anhydrous sulfuric acid. Dried with magnesium. After filtration, it was concentrated and purified by silica gel column chromatography to obtain 7.3 g of transparent viscous liquid mono-O- (5,9,13,17-tetramethyloctadecyl) pentaerythritol. The purity of this product by HPLC analysis was 99.5% or more. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (270 MHz, CDCl ₃ , TMS) δ: 0.83-0.88 (m, 15H), 1.0-1.6 (m, 28H), 2.88 (br.s, 3H) ), 3.39-3.52 (m, 4H), 3.71 (d, J = 3.9 Hz, 6H)

Synthesis Example 8: Synthesis of mono-O- (5,9,13,17-tetramethyloctadecanoyl) pentaerythritol [formula (10)]

  Under a nitrogen atmosphere, one drop of pyridine was added to 10 g of 5,9,13,17-tetramethyloctadecanoic acid and 20 ml of methylene chloride, and 5.2 g of thionyl chloride was added dropwise at room temperature. After completion of the dropwise addition, the mixture was refluxed for 1 hour and concentrated under reduced pressure to obtain 10.5 g of 5,9,13,17-tetramethyloctadecanoic acid chloride.

  3.81 g of pentaerythritol, 2.21 g of pyridine, and 120 ml of dry DMF were mixed and dissolved by heating. After cooling to room temperature, a solution prepared by dissolving 5 g of 5,9,13,17-tetramethyloctadecanoic acid chloride obtained above in 5 ml of methylene chloride was added dropwise, and the mixture was stirred for 1 hour at room temperature. 100 ml of methylene chloride was added to the resulting reaction solution, washed 3 times with saturated brine, and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, 2.50 g of mono-O- (5,9,13,17-tetramethyloctadecanoyl) pentaerythritol was obtained by purification by silica gel column chromatography. The purity of this product by HPLC analysis was 99.5% or more. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (270 MHz, CDCl ₃ , TMS) δ: 0.8-0.9 (m, 15H), 1.0-1.7 (m, 26H), 2.34 (t, J = 7 .4 Hz, 2H), 3.06 (br.s, 3H), 3.63 (d, J = 4 Hz, 6H), 4.17 (s, 2H)

Synthesis Example 9 Synthesis of 1-O- (5,9,13,17-tetramethyloctadecyl) -β-D-xylopyranoside [abbreviation: β-XylC22; Formula (11)]

  1) Under an argon atmosphere, 318 mg of β-xylose tetraacetate was dissolved in 6 ml of dry methylene chloride and cooled to 0 ° C. A solution prepared by dissolving 0.12 ml of tin tetrachloride in 1 ml of methylene chloride was added dropwise thereto, stirred at room temperature for 20 minutes, and then cooled to −10 ° C. A solution prepared by dissolving 326.6 mg of 5,9,13,17-tetramethyloctadecanol in 1 ml of methylene chloride was added dropwise and stirred for 4 hours. Sodium bicarbonate water was added to the reaction mixture, and the mixture was extracted 3 times with methylene chloride. The extract was washed with water and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated and purified by column chromatography to obtain 93 mg of 1-O- (5,9,13,17-tetramethyloctadecyl) -β-D-xylopyranoside triacetate.

  2) In an argon atmosphere, 584.8 mg of 1-O- (5,9,13,17-tetramethyloctadecyl) -β-D-xylopyranoside triacetate was dissolved in 5 ml of dry methanol, and 54 mg of sodium methylate was added. , Stirred. After stirring overnight at room temperature, the mixture was cooled and 1 ml of 1N hydrochloric acid was added dropwise. The reaction solution is concentrated under reduced pressure, and the resulting residue is dissolved in chloroform to form a slurry solution, which is purified by silica gel column chromatography to give 1-O- (5, 9, 13, 17 as a waxy semi-solid. 413 mg of -tetramethyloctadecyl) -β-D-xylopyranoside was obtained. 1-O- (5,9,13,17-tetramethyloctadecyl) -β-D-xylopyranoside is dissolved in an acetic anhydride-pyridine mixed solvent, treated at 60 ° C. for 2 hours, and then purified by gas chromatography. When tested, the purity was 96%. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (300 MHz, CDCl ₃ , TMS) δ: 0.84, 0.86 (d, J = 6.4 Hz, J = 6.8 Hz, 15H), 1.0-1.7 (m, 31H), 3.2-3.7 (m, 5H), 3.82 (dd, J = 16 Hz, 7.7 Hz, 1H), 3.94 (dd, J = 11.6 Hz, 5 Hz, 1H), 4.25 (d, J = 7.1 Hz, 1H)

Synthesis Example 10 Synthesis of 1-O- (3,7,11,15-tetramethylhexadecyl) -α-D-xylopyranoside [Formula (12)]

  3,7,11,15-tetramethylhexadecanol (5.16 g, 17.3 mM) was added to molecular sieve 4A (2 g) dried under an argon atmosphere, stirred for 2 hours, and then dried under reduced pressure. 100 ml of methylene chloride was added to -O-acetyl-β-D-xyloside (5 g, 15.7 mM) under an argon atmosphere, and the mixture was stirred for 10 to 30 minutes. 15.8 ml of 1M tin chloride in methylene chloride was added dropwise and stirred at room temperature for 20 minutes. Next, after cooling the reaction system to 5 ° C., a 20 ml methylene chloride solution of 3,7,11,15-tetramethylhexadecanol (5.16 g, 17.3 mM) was added dropwise over about 30 minutes and left at room temperature. Stirring was continued for 4 hours. The solution was poured into a saturated aqueous sodium hydrogen carbonate solution, extracted three times with 100 ml of methylene chloride, and then washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. Subsequently, the mixture was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate mixed solvent).

  The resulting tetraacetate was dissolved in 5.5 ml of methanol, and 2.5 ml of 0.05 M sodium methylate was added thereto. After stirring at room temperature for 4.5 hours, an equal amount of 1N hydrochloric acid was added to neutralize. The solution was concentrated and purified by silica gel column chromatography (elution solvent: chloroform-methanol mixed solvent) and then dried under reduced pressure to obtain a colorless, transparent and viscous liquid.

  The purity of this liquid was measured. The elemental analysis results for C and H are C: 70.1% (calculated value 69.7%) H: 11.9% (calculated value 11.8%), which is in good agreement with the calculated value from the molecular structure. did. Further, as a result of NMR measurement, the α-isomer purity was at least 97%, and no β-isomer signal was observed. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (300 MHz, CDCl ₃ , TMS) δ: 4.78 (1H, d, J = 3.78 Hz, H1), 4.38 (1H, H5a), 3.83 (1H, H4), 3.09 (1H, d, J = 8.9 Hz, H3), 3.7 (2H, H′1), 3.4-3.8 (5H, H2, H5b, 3 * OH)

Synthesis Example 11 Synthesis of Mono O- (5,9,13-trimethyltetradecyl) pentaerythritol [Formula (13)]

  Under a nitrogen stream, 28.7 g (0.21 mol) of pentaerythritol was dissolved in 200 ml of dry DMF, and 4.22 g (0.11 mol) of 60% NaH was added in several portions while cooling with ice. After the addition, the mixture was stirred at room temperature for 1 hour, heated to 50 ° C., and obtained in the synthesis step of 1-O- (5,9,13-trimethyltetradecyl) erythritol [formula (3)] (5, A half amount of 17.13 g of 9,13-trimethyltetradecyl) tosylate was added dropwise and washed with 55 ml of DMF. After heating to 80 ° C. and stirring for 4 hours, the resulting reaction solution was concentrated under reduced pressure, 500 ml of ether was added to the remaining solution, and the mixture was extracted and dissolved twice, washed twice with saturated brine, and anhydrous sulfuric acid. Dried with magnesium. After filtration, the filtrate was concentrated and purified by silica gel column chromatography to obtain 5.8 g of mono-O- (5,9,13-trimethyltetradecyl) pentaerythritol having the following physical properties. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (300 MHz, CDCl ₃ , TMS) δ: 0.846, 0.867 (d, J = 6.6 Hz, 6.3 Hz, 12H), 1.0-1.6 (m, 21H) , 1.72 (br.s, 1H), 2.68 (br.s, 2H), 3.425 (t, J = 6.5 Hz, 2H), 3.47 (s, 2H), 3.72 (S, 6H)

Synthesis Example 12 Synthesis of 1-O- (3,7,11,15-tetramethylhexadecyl) -β-D-xylopyranoside [β-XP; Formula (14)]

  Under an argon atmosphere, tetra-O-acetyl-β-D-xylopyranoside (5 g, 15.7 mM) and 100 ml of methylene chloride dried under reduced pressure were added to the dried molecular sieve 4A (2 g), and the mixture was stirred for 10 to 30 minutes. . After cooling to 5-8 ° C., 16 ml of 1M tin chloride in methylene chloride was added dropwise and stirred at room temperature for 20 minutes. After cooling to −10 ° C., 16 ml of methylene chloride solution of 3,7,11,15-tetramethylhexadecanol (4.69 g, 15.7 mM) was added dropwise over about 30 minutes, and stirring was continued for 4 hours. It was. The solution was poured into a saturated aqueous sodium hydrogen carbonate solution, extracted three times with 100 ml of methylene chloride, and then washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. Subsequently, the mixture was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate mixed solvent).

  The obtained 1-O- (3,7,11,15-tetramethylhexadecyl) -β-D-xylopyranoside triacetate was dissolved in 5.5 ml of methanol, and 0.05 M sodium methylate 2 .5 ml was added. After stirring at room temperature for 4.5 hours, an equal amount of 1N hydrochloric acid was added to neutralize. The solution was concentrated, purified by silica gel column chromatography (elution solvent: chloroform-methanol mixed solvent), dried under reduced pressure, and 1-O- (3,7,11,15-tetramethylhexadecyl) -β-. D-xylopyranoside [Formula (13)] (white waxy solid) was obtained. NMR measurement showed that 1-O- (3,7,11,15-tetramethylhexadecyl) -α-D-xylopyranoside was not mixed.

Synthesis Example 13 Synthesis of 6-O- (5,9,13,17-tetramethyloctadecanoyl) -L-ascorbic acid [Formula (15)]

  Under an argon stream, 21.0 g (119 mmol) of L-ascorbic acid was dissolved in 90 ml of concentrated sulfuric acid. While stirring, 42.3 g (119 mmol) of methyl 5,9,13,17-tetramethyloctadecanoate was added and allowed to stand at 24-27 ° C. overnight. The obtained uniform solution was poured into 750 ml of ion-exchanged water, extracted with diisopropyl ether, and washed with water. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

  The concentrated solution is purified by silica gel column chromatography, treated with activated carbon in ethanol, filtered, and concentrated to give a pale yellow semi-solid 6-O- (5, 9, 13, 17 having the following NMR spectrum. -Tetramethyloctadecanoyl) Ascorbic acid 9.1g was obtained. The craft point of this product was 0 ° C. or lower. The results of NMR measurement were as follows.

¹ H-NMR spectrum (300 MHz, DMSO-d6, TMS) δ: 11.1 (br.s, 1H), 8.4 (br.s, 1H), 5.3 (br.s, 1H), 4 .67 (s, 1H), 4.06 (m, 2H), 3.97 (m, 1H), 2.3 (m, 2H), 1.6-1.0 (m, 26H),. 9-0.8 (m, 15H)

(Manufacture of creamy skin external preparation)
Each of the skin external preparations of Examples 1 to 6 and Comparative Examples 1 to 6 was mixed with the components shown in Table 1 and Table 2 below, respectively, and an emulsifying disperser (TK homomixer; manufactured by Tokushu Kika Kogyo Co., Ltd.). ) At room temperature at 7000 rpm for 5 minutes to prepare a creamy water-in-oil emulsion composition.

  In addition, the amphiphilic compound mix | blended with the skin external preparation of Examples 1-3 and Comparative Examples 1-3 is mono-O- (5,9,13,17-tetramethyloctadecanoyl obtained according to the synthesis example 8. ) Pentaerythritol [Formula (10)].

  Moreover, the amphiphilic compounds blended in the skin external preparations of Examples 4 to 6 and Comparative Examples 4 to 6 were 1-O- (3,7,11,15-tetramethylhexadeca obtained according to Synthesis Example 3. Noyl) erythritol [1-O- (phytanoyl) erythritol; formula (5)].

In the comparative example, diglyceryl distearate was used as a control amphiphilic compound.
Subsequently, stability and usability | use_condition were evaluated as follows about the prepared skin external preparation.

(Stability evaluation)
After the creamy water-in-oil emulsion composition prepared as described above was stored at 50 ° C. for 1 month, the appearance change was visually observed to evaluate the stability. On the other hand, after the creamy water-in-oil emulsion composition was packed in a resin tube and subjected to a fir test (repeated for 30 minutes with a device that holds the tube 20 times per minute), the appearance change was observed. The stability was evaluated by visual observation. The results determined by the following stability evaluation criteria are shown in Tables 1 and 2 below.
[Stability evaluation criteria]
A: Separation is not observed at all O: Almost no separation is observed Δ: Some separation is observed ×: Separation of water or oil is observed

(Usage evaluation)
Ten expert panelists applied the creamy water-in-oil emulsion composition to the back of the hand, and judged the feeling of use. The results determined according to the following usability evaluation criteria are shown in Tables 1 and 2 below.
[Usage Evaluation Criteria]
◎: Evaluated when 8-10 people out of 10 are refreshed ○: Evaluated when 5-7 people out of 10 are refreshed △: Evaluated when 3-4 people out of 10 people are refreshed x: Evaluation that 0 to 2 out of 10 people are refreshing Tables 1 and 2 show the results of the evaluation together with the blending amounts of the respective components.

  As shown in Tables 1 and 2, compared with the comparative example, the skin external preparations of the examples were much more stable and had a good usability.

(Example 7: Production of emulsion)
The emulsion of Example 7 was produced according to the following formulation according to the following preparation method.
Prescription Mass%
Oil phase Dimethylpolysiloxane (6CS) ^* 2.0
Behenyl alcohol ^* 1.0
Batyl alcohol ^* 0.5
Hardened oil ^* 3.0
Squalane [hydrocarbon oil] ^* 6.0
Tetra-2-ethylhexanoic acid pentaerythrit ^* 2.0
Polyoxyethylene glyceryl isostearate 1.0
Amphiphilic compound of formula (10) [Synthesis Example 8] 5.0
Retinol acetate 0.5
Perfume Appropriate amount of water phase Glycerin 5.0
1,3-butylene glycol 7.0
Erythritol 2.0
Sodium glutamate 2.0
Carboxyvinyl polymer 0.1
Potassium hydroxide appropriate amount Phenoxyethanol appropriate amount
Purified water residue (about 62%)
*: Oil content

(Preparation method)
The above oil phase components were mixed and dissolved at 70 ° C., and emulsified by applying a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.) while adding the water phase components mixed and dissolved at 70 ° C. to the oil phase components. After emulsification, the emulsion was cooled to room temperature with stirring to obtain an emulsion.

(Example 8: Production of emulsion-2)
The emulsion of Example 8 was produced by the following preparation method according to the following formulation.
Prescription Mass%
Oil phase Decamethylcyclopentasiloxane ^* 15.0
Trimethylsiloxysilicate 5.0
Macadamia nut oil ^* 2.0
Squalane [hydrocarbon oil] ^* 2.0
Cholesteryl hydroxystearate ^* 0.5
Cetyl 2-ethylhexanoate ^* 2.0
2-Ethylhexyl paramethoxycinnamate 7.5
Glucose ascorbate 0.3
Tocopherol acetate 0.1
Amphiphilic compound of formula (9) [Synthesis Example 7] 0.5
POE (10) methylpolysiloxane copolymer 5.0
Organically modified bentonite 5.0
Aqueous phase Glycerin 5.0
1,3-butylene glycol 5.0
Maltitol solution 2.0
Sodium chondroitin sulfate 0.01
Sodium hyaluronate 0.1
Fish collagen 0.4
Edetate trisodium 0.05
Paraben appropriate amount
Purified water residue (about 42%)
*: Oil content

(Preparation method)
The above oil phase components were mixed and dissolved at 70 ° C., and emulsified by applying a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.) while adding the water phase components mixed and dissolved at 70 ° C. to the oil phase components. After emulsification, the emulsion was cooled to room temperature with stirring to obtain an emulsion.

(Example 9: Production of cosmetic cream-1)
The cosmetic cream of Example 9 was produced by the following preparation method according to the following formulation.
Prescription Mass%
Oil phase Liquid paraffin [Hydrocarbon oil] ^* 8.0
Vaseline ^* 3.0
Dimethylpolysiloxane (6CS) ^* 2.0
Stearyl alcohol ^* 3.0
Behenyl alcohol ^* 2.0
Tetra-2-ethylhexanoic acid pentaerythrit ^* 4.0
Polyisoethylene glyceryl monoisostearate 2.0
Polyoxyethylene glycerol monostearate 1.0
Lipophilic glyceryl monostearate 2.0
Oil-soluble licorice extract 0.1
Retinol palmitate 0.25
Tocopherol acetate 0.1
Amphiphilic compound of formula (5) [Synthesis Example 3] 10.0
Perfume Appropriate amount of water phase Glycerin 5.0
Dipropylene glycol 4.0
Trehalose 1.0
Carboxyvinyl polymer 0.05
Potassium hydroxide 0.015
Appropriate amount of phenoxyethanol
Purified water residue (about 52%)
*: Oil content

(Preparation method)
The above oil phase components were mixed and dissolved at 70 ° C., and emulsified by applying a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.) while adding the water phase components mixed and dissolved at 70 ° C. to the oil phase components. After emulsification, the product was cooled to room temperature with stirring to obtain a cosmetic cream.

(Example 10: Production of cosmetic cream-2)
The cosmetic cream of Example 10 was produced by the following preparation method according to the following formulation.
Prescription Mass%
Oil phase Methylphenylpolysiloxane ^* 5.0
Stearyl alcohol ^* 2.0
Stearic acid ^* 1.5
Palmitic acid ^* 1.0
Glyceryl tri-2-ethylhexanoate ^* 4.0
Self-emulsifying glyceryl monostearate 1.0
Octyl methoxycinnamate 6.0
Petrolatum [hydrocarbon oil] ^* 2.0
Tranexamic acid 2.0
Squalane [hydrocarbon oil] ^* 3.0
Amphiphilic compound of formula (10) [Synthesis Example 8] 3.0
Aqueous phase Glycerin 5.0
Dipropylene glycol 5.0
Sorbit liquid (70%) 5.0
Potassium hydroxide 0.15
Sodium citrate 0.1
Xanthan gum 0.2
Paraben appropriate amount
Purified water residue (about 54%)
*: Oil content

(Preparation method)
The above oil phase components were mixed and dissolved at 70 ° C., and emulsified by applying a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.) while adding the water phase components mixed and dissolved at 70 ° C. to the oil phase components. After emulsification, the product was cooled to room temperature with stirring to obtain a cosmetic cream.

(Evaluation of stability and usability)
For the emulsions of Examples 7 to 8 and the cosmetic creams of Examples 9 to 10 prepared as described above, stability and usability were evaluated in the same manner as in Examples 1 to 6 and Comparative Examples 1 to 6. The results are shown in Table 3.

  It was shown that the external preparations for skin (milky lotion, cosmetic cream) of any Example have high stability and good usability.

  From the above results, it was shown that the external preparation for skin of the present invention can maintain a stable emulsified state for a long period of time, has a good feeling of use, and brings a refreshing feel.

  Since the external preparation for skin of the present invention has high stability and good usability, it can be suitably used for cosmetics, pharmaceuticals, quasi drugs, bathing agents, wiping agents, and the like.

Claims (4)

An external preparation for skin comprising a water-in-oil emulsion composition comprising at least one amphiphilic compound represented by the following general formula (1) or (2) and an oil component, the composition comprising an amphiphilic compound: The skin external preparation whose content is 0.1-20 mass%.

(In the formula, n and n ′ represent an integer of 0 to 4, m and m ′ represent an integer of 0 to 3, and R and R ′ are selected from the group consisting of erythritol, pentaerythritol, xylose, and ascorbic acid. It is a residue obtained by removing one hydroxyl group from any one of The amphiphilic compound is one having a Krafft point of less than 6 ° C., skin external preparation according to claim 1. The skin external preparation according to claim 1 or 2 , wherein the oil component is at least one selected from the group consisting of silicone oil, ester oil, hydrocarbon oil, fats and oils, and waxes. The external preparation for skin according to any one of claims 1 to 3 , further comprising a physiologically active substance.