JPH0338242B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to external preparations, and more particularly, the present invention relates to external preparations that contain a specific diacylglycerin, have high skin affinity (good compatibility with the skin), and have excellent skin moisturizing effects for a long time. Related to external preparations such as skin cosmetics, hair cosmetics, and external medicines. [Conventional technology and its problems] The stratum corneum of normal skin normally contains 10 to 30% water and maintains elasticity and flexibility, but due to environmental conditions etc. % or less, a condition called so-called dry skin occurs. For example, symptoms such as cracks and chapping occur during dry winter months. Furthermore, as we age, the secretion of sebum decreases, making the skin more prone to dryness, leading to symptoms such as senile xeroderma, which causes itching and scaling. Conventional methods to solve these problems include using moisturizers to enhance skin hydration and using oils to suppress transepidermal water loss (TEWL). As examples of the former, moisturizers such as glycerin, propylene glycol, and sodium pyrrolidone carboxylate have been used, but when applied to the skin, the effects of these moisturizers are temporary and long-lasting. However, it had the disadvantage of being susceptible to external environmental conditions. On the other hand, Vaseline ointment is a well-known example of the latter, but in order to increase its effectiveness, it is necessary to apply a large amount of ointment. It has a dry and unpleasant feel, and conversely, if the amount applied is small, the number of occlusions is low and it is not sustainable. [Means for Solving the Problems] In view of these circumstances, the present inventors conducted intensive research to obtain an external preparation that has high skin affinity and excellent long-lasting skin moisturizing effects. The present invention was completed based on the discovery that by blending diacylglycerin having an acyl residue with myristic acid (tetradecanoic acid), it has good compatibility with the skin and has an excellent long-term skin moisturizing effect. That is, the present invention provides an external preparation characterized by containing diacylglycerin represented by the following general formula (). [Wherein, one of R ₁ , R ₂ , and R ₃ is () a methyl branched isostearic acid residue represented by the following formula, (In the formula, m and n are each integers of 4 to 10,
m+n=14, and has a distribution centered at m=n=7. ) () 5,7,7-trimethyl-2-(1,3,
The branched saturated fatty acid residues are selected from the group consisting of 3-trimethylbutyl)-octanoic acid residues and ()2-heptylundecanoic acid residues, one of which is a tetradecanoic acid residue and the rest of which are hydrogen. ] The diacylglycerin represented by the general formula () used in the present invention has a branched saturated fatty acid residue having 18 carbon atoms (isostearic acid residue) and a tetradecanoic acid residue in one molecule, for example, the following: It can be synthesized by the following method. (1) Direct esterification of glycerin with fatty acids. It is produced by the usual method of producing acylglycerin from a branched saturated fatty acid having 18 carbon atoms, tetradecanoic acid (myristic acid), and glycerin. For example, if the above branched saturated fatty acids, myristic acid, and glycerin are mixed in equimolar amounts, 200~
These acylglycerol mixtures are formed by heating to 230° C. and removing the water formed under reduced pressure. A diacylglycerol fraction can be obtained by distilling or column chromatographically treating this product. However, this diacylglycerin is a random mixture; that is, diacylglycerin consisting only of branched saturated fatty acid residues, diacylglycerin consisting of branched saturated fatty acid residues and myristic acid residues, and diacylglycerin consisting only of myristic acid residues. Since it is a mixture, the desired diacylglycerin of the present invention can be obtained by a recrystallization method using a solvent such as hexane by utilizing the difference in melting point. The branched saturated fatty acid having 18 carbon atoms used for producing the diacylglycerin of the present invention can be easily obtained from petrochemical raw materials or oleochemical raw materials. That is, 5,7,7-trimethyl-2-(1,
3,3-trimethylbutyl)-octanoic acid is
It can be produced by oxo-reacting an isobutylene dimer to form a branched aldehyde having 9 carbon atoms, followed by aldol condensation of this aldehyde to form a branched unsaturated aldehyde having 18 carbon atoms, followed by hydrogenation and oxidation. It is commercially available from Nissan Chemical Co., Ltd. 2-heptylundecanoic acid can be produced by subjecting nonyl alcohol to a Guerbet reaction and then oxidizing it, and is commercially available, for example, from Mitsubishi Kasei Corporation. Methyl branched isostearic acid is obtained as a by-product during the production of oleic acid dimer [for example, J.Amer.Oil Chem. Soc., 51 , 522].
(1974)] and is commercially available, for example, from Emery Co., Ltd. in the United States. (2) Reaction of reactive derivatives of fatty acids with monoglycerides. As a more advantageous production method, either branched saturated fatty acid or myristic acid can be converted into a more reactive derivative and then esterified. One of the highly reactive derivatives is an acid halide of a fatty acid, and in a preferred example of this process, first, 1 to 5 mol, preferably 1 to 5 mol per mol of the branched saturated fatty acid, is added to the raw branched saturated fatty acid. 1 to 2 mol of halogenating reagents such as thionyl chloride, thionyl bromide, phosphorus trichloride, etc.
The reaction is carried out at ~100°C, preferably 20-80°C, leading to the acid halide. Myristoylglycerin is obtained by heating 1 mole of myristic acid and 1 mole of glycerin to 200-230°C and removing the water produced under reduced pressure. Monomyristoylglycerin is obtained by molecularly distilling this product. Therefore, the above-mentioned branched saturated fatty acid halide and 0.5 to 3 mol, preferably 1 to 1.5 mol of monomyristoylglycerin are added to the acid halide, and 1 to 3 mol, preferably 1 to 1.5 mol, per mol of branched saturated fatty acid halide. Using dehydrohalogenating agents such as pyridine and quinoline, for example, benzene, toluene, xylene,
The reaction is carried out in a suitable inert solvent such as hexane (1 to 10 times the volume, preferably (3 to 5 times the volume) of the acid halide) at 50 to 100°C, preferably 60 to 80°C with stirring while heating. The desired diacylglycerin containing branched saturated fatty acid residues and myristic acid residues can be obtained by molecular distillation or column chromatography of the acylglycerin from which the hydrogen halide amine salt has been removed. ( 3) Method using lipase. A more advantageous production method is to use lipase to produce the product without going through highly reactive derivatives. First, 1 mol of branched saturated fatty acid and 1 mol of glycerin are heated at 200 to 230°C. By heating to and removing the produced water under reduced pressure, acylglycerin having branched saturated fatty acid residues is obtained, and through molecular distillation, monoacylglycerin having branched saturated fatty acid residues is obtained.This monoacylglycerin By blending equimolar amounts of and myristic acid and carrying out an esterification reaction using lipase as a catalyst, the desired diacylglycerol containing branched saturated fatty acid residues and myristic acid residues can be obtained.Depending on the degree of esterification, Depending on the situation, molecular distillation is carried out as a post-treatment.For example, if the esterification rate of myristic acid is low, it is necessary to remove the remaining myristic acid and monoacylglycerol.In addition, by-products of triacylglycerin can also be removed by molecular distillation column. Can be removed by chromatography.When lipase is used as a catalyst,
Lipases with α-position selectivity or lipases selective for partial glycerides are most effective. As shown in Table 1, the amount of diacylglycerin in the external preparation of the present invention can vary widely depending on the dosage form, but is generally in the range of 0.1 to 90% by weight, preferably 0.1 to 50% by weight. On the other hand, raw materials other than water used in the present invention include oils, surfactants, humectants containing polyhydric alcohols, various medicinal agents, preservatives, fragrances, etc. that are usually applied to external preparations. , most of the ingredients are mentioned, and are appropriately selected and blended depending on the purpose, use, dosage form, etc. For example, for oil, stearic acid, myristic acid, cetanol,
Solid fats such as stearyl alcohol, cholesterol, petrolatum, squalane, cholesteryl isostearate, jojoba oil, olive oil,
There are liquid fats such as neopentyl glycol dicaprate and liquid paraffin. On the other hand, examples of polyhydric alcohols include glycerin, 1,3-butylene glycol, propylene glycol, dipropylene glycol, and polyethylene glycol. Furthermore, regarding surfactants, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyethylene glycol fatty acid ester, alkyl glyceryl ether, fatty acid salt,
Examples include alkyl phosphates. Further, external preparations to which the present invention is applied include ointments, creams, emulsions, lotions, etc., and the amounts shown in Table 1 below are usually suitable. In addition, in Table 1, the blending ratio is in weight %.

〔Effect of the invention〕

The diacylglycerin represented by the general formula () used in the present invention is liquid at room temperature, has excellent oxidative stability, has extremely low decomposition, is mildly irritating, and has an excellent feel to the skin and hair. In other words, to simply obtain liquid diacylglycerin, it is sufficient to use an unsaturated fatty acid such as oleic acid as the fatty acid residue, or a short chain fatty acid such as octanoic acid, but if only unsaturated fatty acids are used, the oxidative stability is reduced. However, when only short chain fatty acids are used, irritation becomes a problem. On the other hand, 1
The diacylglycerin of the present invention, which has both a branched saturated fatty acid residue having 18 carbon atoms and a tetradecanoic acid residue in the molecule, does not have these problems. Since the external preparation of the present invention containing such diacylglycerin does not contain a crystalline component, it has good compatibility with the skin and has an excellent long-lasting skin moisturizing effect. [Example] The present invention will be explained in more detail by showing examples of the present invention below, but the present invention is not limited to these examples. In addition, the method for producing monoacylglycerol of branched saturated fatty acids and myristic acid and the branched saturated fatty acid halide is also used as a reference example, and the method for producing diacylglycerol having branched saturated fatty acid residues and myristic acid residues according to the present invention. is shown as a synthesis example. Reference Example 1 Isostearic acid {5,7,7-trimethyl-2-(1,3,3-trimethylbutyl)octanoic acid) was placed in a reaction vessel, container 2, equipped with a thermometer, a reflux condenser, a dropping funnel, and a stirrer. , manufactured by Nissan Chemical Co., Ltd.
568g (2.0mol) was charged. Add thionyl chloride 286 from the dropping funnel while stirring and under nitrogen gas flow.
g (2.4 mol) was added dropwise at room temperature. As the dropwise addition of thionyl chloride progressed, the reaction mixture turned colorless, pale yellow, and blackish brown, and at the same time, gas generation was observed. The temperature of the reaction mixture was kept at room temperature during the dropwise addition of thionyl chloride. After adding thionyl chloride dropwise over a period of approximately 3 hours, the reaction mixture was heated to 60°C in an oil bath.
It was kept at ~70°C for about 3 hours. After confirming that almost no gas generation was observed, low-boiling substances were distilled off under reduced pressure, and then vacuum distillation was performed. 112~120℃/
588 g (97% yield) of a fraction of 0.1 to 0.3 mmHg was obtained.
This product is 5,7,7-trimethyl-2-(1,
It was 3,3-trimethylbutyl)octanoyl chloride. IR spectrum (liquid film method) 2970, 2920, 2875, 1795 (C=0 stretching), 1480,
1390, 1370, 1260, 1210, 995, 930, 790, 710,
600 cm ^-1 H ¹ -NMR spectrum (CCl ₄ solvent): δ 0.9 (s, 24H, CH ₃ -) 1.1-2.0 (m, 10H, -CH ₂ - and

[Formula]) 2.5 (m, 1H, C H COCl) Reference Example 2 Using a reaction vessel with a capacity of 3 equipped with the same equipment as that used in Reference Example 1, isostearic acid (methyl branched fatty acid represented by the following formula) Emery 875 (isostearic acid) 568 from Emery, USA
g (2.0 mol) of thionyl chloride 520 g (4.4 mol)
was reacted in the same manner as in Reference Example 1. (In the formula, m and n are each an integer of 4 to 10, m+
n=14, and has a distribution centered at m=n=7. After the reaction, remove low-boiling substances under reduced pressure to obtain approximately 230g.
A low-boiling substance believed to be thionyl chloride was recovered.
Then, by vacuum distillation, the temperature was reduced to 153-170℃/1.0-0.3mm.
454 g of Hg fraction (yield 75%) was obtained. This was methyl branched isostearic acid chloride. IR spectrum (liquid film method) 2950, 2920, 2550, 1800 (C=0 stretching), 1460,
1400, 1380, 950, 720, 680, 590 cm ^-1 H ¹ -NMR spectrum (CCl ₄ solvent): δ 0.6-1.0 (m, -CH ₂ - and

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

[Formula]) 2.77 (t, C H ₂ COCl) Reference Example 3 In a reaction vessel with a capacity of 2 equipped with a thermometer, nitrogen capillary, reflux condenser (with water separation tube), and stirrer,
568 g (2.0 mol) of 2-heptylundecanoic acid, 184 g (2.0 mol) of purified glycerin, and 1.2 g of calcium hydroxide were charged and heated at 230 to 240°C under nitrogen gas aeration.
Esterification was performed at After about 10 hours, it was confirmed that almost no water was produced, and the distillation was switched to vacuum distillation to remove unreacted glycerin under conditions of 210-220°C/15-25 mmHg. After almost no distilled glycerin was observed, the reaction mixture was distilled using a thin-film molecular distillation device to obtain a concentration of 170 to 175
246 g of a fraction with a temperature of 0.03 to 0.05 mmHg was obtained. This product was monoacylglycerin of 2-heptylundecanoic acid. IR spectrum (liquid film method) 3440 (OH stretching), 2960, 2910, 2860, 1740 (C
= 0 stretch), 1470, 1370, 1160, 740 cm ^-1 H ¹ -NMR spectrum (CCl ₄ solvent): δ 0.9 (t, 6H, CH ₃ -) 1.1-1.6 (m, 28H, -CH ₂ - ) 2.3 (m, 1H,

[Formula]) 2.7 (s, 2H, -O- H ) 3.5-4.2 (m, 5H, -C H ₂ -O- and C H -
O-) Hydroxyl value 311.8 (calculated value 312.9) Reference example 4 458 g (2.0 mol) of myristic acid was placed in a reaction vessel with a capacity of 2 and equipped with the same equipment as used in Reference example 3.
184 g (2.0 mol) of purified glycerin and 0.9 g of calcium hydroxide were added, and heated to 230 ~
The esterification reaction was carried out at 240°C for about 8 hours. Next, switch to vacuum distillation 210-220℃/15-25mmHg
Unreacted glycerin was removed under the following conditions. After distilled glycerin was no longer observed, the reaction mixture was distilled using a thin film molecular distillation device to obtain a concentration of 195-200%.
230 g of a fraction having a temperature of 0.03 to 0.05 mmHg was obtained. This material was monomyristoylglycerin. Hydroxyl value: 370.3 (calculated value: 371.0) Synthesis Example 1 303 g (1 mol) of monomyristoylglycerin obtained in Reference Example 4 and benzene were placed in reaction vessel 3 equipped with a thermometer, dropping funnel, reflux condenser, and stirrer.
1000 ml and 87 g (1.1 mol) of pyridine were added in this order. The reaction mixture was heated to 50°C in an oil bath under nitrogen gas while stirring, and then 5,7,7-trimethyl-2- obtained in Reference Example 1 was added through the dropping funnel.
291 g (0.96 mol) of (1,3,3-trimethylbutyl)octanoyl chloride was added dropwise over a period of about 3 hours while maintaining the temperature of the reaction mixture at about 50°C. After the dropwise addition was completed, the mixture was heated to 60 to 80°C and stirred for about 5 hours. 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, followed by heating at 190 to 200°C for about 5 hours under reduced pressure of 0.5 to 0.7 mmHg. The slight remaining acid chloride was completely removed. The obtained product contains 5,7,7-trimethyl-2-(1,3,3-
It is a mixture of diacylglycerin and triacylglycerin in which one or two molecules of trimethylbutyl)octanoic acid are acylated and unreacted monomyristoylglycerin. This mixture was subjected to column chromatography (Wakogel B-
10 (manufactured by Wako Pure Chemical Industries, Ltd.) (hexane/diethyl ether = 70:30) to obtain 360 g of diacylglycerin fraction. This is a colorless and transparent liquid with 5,7,7-trimethyl-2-(1,3,
It is a diacylglycerin containing 3-trimethylbutyl)octanoic acid and myristic acid as fatty acid residues. IR spectrum (liquid film method) 3500 (OH stretching), 2960, 2930, 2850, 1740 (C
= 0 stretch), 1465, 1365, 1160, 720 cm ^-1 H ¹ -NMR spectrum (CCl ₄ solvent): δ 0.9 (s, 27H, -C H ₃ ) 1.2-1.6 (m, 22H, -C H ₂ - as well as

【formula】) 2.3 (m, 3H,

[Formula], -C H ₂ - CO-) 2.9 (s, 1H, -OH ) 4.0-4.5 (m, 4H, -C H ₂ -O-) 5.1 (m, 1H, C H -OH) Acid Value 0.1 (calculated value 0) Hydroxyl value 98.0 (calculated value 98.6) Synthesis Example 2 Into a reaction vessel with a capacity of 3 equipped with the same equipment as that used in Synthesis Example 1, 303 g of monomyristoylglycerin obtained in Reference Example 4 (1 mole), benzene 1500
ml and 100 g (1.27 mol) of pyridine were added in this order. While stirring, the mixture was heated to 50°C in an oil bath under nitrogen gas flow, and 291 g of the methyl branched isostearic acid chloride obtained in Reference Example 2 was poured into the dropping funnel.
(0.96 mol) was added dropwise. After the addition was completed, the reaction mixture was kept at 50°C for about 3 hours and then at 70-80°C for about 8 hours. As a result of this heat treatment, the esterification reaction proceeded completely, and it was confirmed by the IR spectrum that no acid chloride was contained in the reaction mixture. Diacylglycerin 372, which is treated in the same manner as in Synthesis Example 1 and has methyl branched isostearic acid and myristic acid as fatty acid residues, is a colorless and transparent liquid.
I got g. IR spectrum (liquid film method) 3480 (OH stretching), 2955, 2930, 2850, 1740 (C
= 0 stretch), 1465, 1365, 1160, 720 cm ^-1 H ¹ -NMR spectrum (CCl ₄ solvent): δ 0.9 (m, 9H, -C H ₃ ) 1.2-1.6 (m, 49H, -C H ₂ - ,

[Formula]) 2.3 (m, 4H, -C H ₂ -CO-) 2.9 (s, 1H, -OH ) 4.0~4.5 (m, 4H, -C H ₂ -O-) 5.1 (m, 1H, C H -OH) Acid value 0.1 (calculated value 0) Hydroxyl value 97.4 (calculated value 98.6) Synthesis example 3 Capacity 2 equipped with thermometer, reflux condenser, and stirrer
359 g (1 mol) of monoacylglycerin of 2-heptylundecanoic acid obtained in Reference Example 3 was placed in a reaction vessel.
274 g (1.2 mol) of myristic acid, commercially available lipase preparation Lipozyme 3A {lipase of Mucor miehei origin immobilized on anion exchange resin, manufactured by Novo Industries A.S.} 80 g
added. The mixture was heated to 50°C and stirred for 5 hours under reduced pressure of 100 to 300 mmHg to carry out an esterification reaction. After the reaction is complete, filter the lipase preparation and remove the reaction product from the filtrate.
Excess myristic acid and unreacted monoacylglycerin are removed by distillation using a thin-film molecular distillation device under conditions of 190-195°C and 0.03-0.05 mmHg, and the desired 2-heptylundecanoic acid and myristic acid are obtained. 501 g of diacylglycerin as a residue was obtained. IR spectrum (liquid film method) 3480 (OH stretching), 2960, 2930, 2850, 1740 (C
= 0 stretching), 1465, 1365, 1160, 720 cm ^-1 H ¹ -NMR spectrum (CCl ₄ solvent): δ 0.9 (m, 9H, -C H ₃ ) 1.2-1.6 (m, 50H, -C H ₂ - ) 2.3 (m, 3H, CH -CO- , -CH ₂ -CO-) 2.7 (s, 1H, -OH ) 4.0-4.5 (m, 4H, -CH 2 -O-) 5.1 ( _m , 1H, C H -OH) Acid value 0.1 (calculated value 0) Hydroxyl value 97.1 (calculated value 98.6) Example 1 (Ointment) <Oil phase component> Vaseline 40% by weight Squalane 10 The present invention obtained in Synthesis Example 2 diacylglycerin
20 POE (20) Sorbitan monostearate 3 Butylparaben 0.1 <Water phase component> Methylparaben 0.2% by weight Glycerin 10 Water Balance An ointment was prepared by the following manufacturing method using the oil phase component and water phase component of the above composition. <Preparation method> Add methylparaben and glycerin to water, heat, and keep the aqueous phase at 70°C. Meanwhile, other lipophilic components are mixed and dissolved by heating, and the oil phase is brought to 70°C. Next, this oil phase is added to the water phase and emulsified using an emulsifying machine. The ointment of the present invention was prepared by cooling the emulsion to a final temperature of 30° C. using a heat exchanger and then filling the emulsion. The obtained ointment of the present invention has high skin affinity,
It was also an external preparation with excellent long-lasting skin moisturizing effects. Example 2 (Cream) <Oil phase components> Stearic acid 2% by weight Setanol 1 Cholesterol 1 Squalane 10 Jojoba oil 10 Diacylglycerin of the present invention obtained in Synthesis Example 1
10 POE (40) Hydrogenated castor oil 0.5 Cetyl phosphate 0.5 Sorbitan monostearate 2.0 Butylparaben 0.1 <Aqueous phase components> Methylparaben 0.2% by weight Glycerin 10 1,3-butylene glycol 5 Fragrance 0.1 Potassium hydroxide 0.1 Water Balance of the above composition A cream was prepared using the oil phase component and the water phase component by the following manufacturing method. <Production method> Mix the above aqueous phase components and heat to dissolve the aqueous phase.
Keep at 70℃. The above-mentioned oil phase components are similarly heated and mixed at 70°C, and the above-mentioned oil phase is added to this aqueous phase and emulsified using an emulsifying machine. By cooling the emulsion to a final temperature of 30℃ using a heat exchanger and then filling it,
A cream of the invention was prepared. The obtained cream of the present invention was an external preparation with high skin affinity and excellent long-lasting skin moisturizing effect. Example 3 (Emulsion) <Oil phase component> Setanol 1% by weight Squalane 5 Olive oil 3 Jojoba oil 2 Diacylglycerin of the present invention obtained in Synthesis Example 3
5 POE (10) Hydrogenated castor oil 1 Sorbitan monostearate 1 Butylparaben 0.1 <Aqueous phase components> Methylparaben 0.1% by weight Glycerin 2 1,3-Butylene glycol 2 Ethanol 3 Fragrance 0.1 Water Balance Oil phase components of the above composition and water An emulsion was prepared in the same manner as in Example 2 using the phase components. The obtained emulsion of the present invention has high skin affinity,
It was also an external preparation with excellent long-lasting skin moisturizing effects. Example 4 (Lotion) <Oil phase component> Diacylglycerin of the present invention obtained in Synthesis Example 2
2% by weight POE (60) hydrogenated castor oil 1 <Aqueous phase components> Lactic acid Appropriate amount Sodium lactate Appropriate amount Glycerin 3% by weight 1,3-Butylene glycol 1.5 Polyethylene glycol 1500 0.5 Ethanol 10 Fragrance 0.1 Water Balance Oil phase components of the above composition A lotion was prepared according to the following manufacturing method using the and aqueous phase components. <Production method> Dissolve glycerin, 1,3-butylene glycol, polyethylene glycol 1500, lactic acid, sodium lactate, and ethanol in water to make it weakly acidic (PH5-6)
Make it. A lotion of the present invention was prepared by dissolving polyoxyethylene hydrogenated castor oil, the diacylglycerin of the present invention obtained in Synthesis Example 2, and a fragrance. The obtained lotion of the present invention was an external preparation with high skin affinity and excellent long-term skin moisturizing effect.

Claims (1)

[Scope of Claims] 1. An external preparation characterized by containing diacylglycerin represented by the following general formula (). [Wherein, one of R ₁ , R ₂ , and R ₃ is () a methyl branched isostearic acid residue represented by the following formula, (In the formula, m and n are each integers of 4 to 10,
m+n=14, and has a distribution centered at m=n=7. ) () 5,7,7-trimethyl-2-(1,3,
The branched saturated fatty acid residues are selected from the group consisting of 3-trimethylbutyl)-octanoic acid residues and ()2-heptylundecanoic acid residues, one of which is a tetradecanoic acid residue and the rest of which are hydrogen. ]