JPH0733323B2 - External skin preparation - Google Patents

Description

TECHNICAL FIELD The present invention relates to a skin external preparation related to cosmetics, pharmaceuticals, quasi-drugs, toiletry products and the like.

[Conventional technology]

In recent years, a lot of researches on emulsification have been carried out, new emulsifiers and emulsification technology have made remarkable progress, and an emulsion composition (emulsion) having very good stability has been developed and widely used in various fields as an external preparation for skin. I came here.

Conventionally, the external skin preparations should have the following characteristics: (1) No skin irritation and high safety (2) Good stability and long-term storage (3) Good feel during use, and appropriate emollient property (4) It can be mentioned that the skin has an appropriate amount of moisturizing properties, but in order to develop such properties, the types of raw materials including surfactants are selected and the composition is designed. However, achieving that goal is not easy. For example, ether-type nonionic surfactants such as ethylene oxide adducts of higher aliphatic alcohols and higher fatty acid soaps exhibiting weak alkalinity generally cause problems such as skin irritation. Ester type nonionic surfactants are poor in emulsifying properties, and external preparations for skin using higher fatty acid soap as an emulsifier have drawbacks such as large foaming property when applied to the skin and whiteness does not disappear forever. ing.

[Problems to be solved]

As described above, the conventional techniques have a problem in that a skin external preparation that is satisfactory in various aspects such as safety for skin, stability of emulsion, moisturizing property, foaming property, and feeling of use cannot be obtained.

[Means for solving problems]

In order to solve the above problems, the present invention provides an ester of 4,5-dicarboxy-4-pentadecanolide and a polyhydroxy compound and a salt thereof and a lactone ring of 4,5-dicarboxy-4-pentadecanolide. Done 3-
A means for external application to the skin is adopted which comprises at least one of the four components of an ester of hydroxy-1,3,4-tetradecanetricarboxylic acid and a polyhydroxy compound and a salt thereof. The details will be described below.

First, 4,5-dicarboxy-4-pentadecanolide (also known as spiculisporic acid, hereinafter abbreviated as S acid) in the present invention has a high yield as a metabolite of penicillium spiculisporum by a microbial reaction using glucose as a raw material. Is a substance mass-produced at a rate The substance has a melting point of 143 to 146 ° C., an acid value of 336.9, a saponification value of 515.1, and an iodine value of 0.5 or less.

Next, the polyhydroxy compound in the present invention is a polyhydric alcohol having two or more hydroxyl groups in the molecule, for example, glycerin, diglycerin, triglycerin or other polyglycerin, or inositol, lactose, saccharose, Glucose, fructose, xylitol, mannitol, maltitol,
Examples thereof include sugars such as sorbitol and pentaerythritol, and glycols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol and hexylene glycol. Then, such a polyhydroxy compound and the S
In order to obtain spiculisporic acid ester (hereinafter abbreviated as S acid ester) from an acid, dehydration reaction may be carried out at an arbitrary molar ratio. 130
0) or 1 to 2 mol of ethylene glycol is charged into a reactor, and the dehydration reaction is carried out at a reaction temperature of 110 to 170 ° C. and a reaction pressure of 50 mmHg or less under reduced pressure or normal pressure for a reaction time of 2 to 5 hours. Such an S-ester was obtained. The viscosities in Table 1 were measured with a B-type viscometer, and the-mark means that the viscosity was too high to measure. The surface tension was 20 ° C measured by a Wilhelmy surface tensiometer.
The foaming power is the 1% concentration by the loss-miles method, the value at 20 ° C., and the values in parentheses are the measured values after 5 minutes.

The ester of 3-hydroxy-1,3,4-tetradecanetricarboxylic acid (hereinafter abbreviated as O acid) and the polyhydroxy compound (hereinafter abbreviated as O acid ester) of the present invention is the S acid. The ester can be obtained by opening only the lactone ring under appropriate conditions. It can be obtained by adding excess sodium hydroxide aqueous solution to S acid, heating and then neutralizing with acid. It can also be obtained by dehydrating the O acid and polyhydroxy compound.

Further, the respective salts of such S acid ester and O acid ester include, for example, sodium salt, potassium salt, lithium salt, ammonium salt, calcium salt, magnesium salt and other inorganic salts, lysine, arginine, histidine, ornithine and the like. Examples thereof include salts with basic amino acids, basic oligopeptides containing these basic amino acids as constituents, salts with monoethanolamine, diethanolamine, triethanolamine and other basic amines. The salt may be separately generated in advance, or may be generated in the process of manufacturing the external preparation for skin.

The four components of the S acid ester, the O acid ester and salts thereof described above have a hydrophilic / lipophilic balance depending on the presence or absence of salt formation and the degree thereof, the type of salt, the type of polyhydroxy compound, the degree of ester substitution and the like. (HLB) can be adjusted arbitrarily, and the emulsified area can be expanded over a wide range. That is, since the S acid ester and its salt and the O acid ester and its salt of the present invention are both a polybasic acid type surfactant and an ester type nonionic surfactant, an aqueous phase component coexisting with them and It exhibits an excellent surface-active effect on both components of the oil phase.

The aqueous phase component used in the present invention is water, monohydric alcohols such as ethanol, propanol, isopropanol, butanol, ethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, and hexylene. Glycol, glycerin,
Diglycerin, triglycerin or glucose, maltose, maltitol, sucrose, sorbitol and other polyhydric alcohols having two or more hydroxyl groups in the molecule, and other conventional fields such as cosmetics, quasi-drugs, pharmaceuticals and toiletry products In the aqueous phase component which has already been used in general, even if two or more of these substances are used in combination, this invention is not hindered. The oil phase component used in the present invention is liquid paraffin, squalane, liquid or semi-solid (grease) hydrocarbons such as petrolatum or octyldodecyl myristate, isopropyl palmitate, cetyl-2-ethylhexanoate, Ester oils such as glyceryl-tri-2-ethylhexanoate, vitamin E acetate, vitamin A palmitate, vitamin C stearate, solid paraffin, microcrystalline wax, ceresin wax, beeswax,
Wax such as whale wax, vegetable oil such as olive oil, soybean oil, safflower oil, rice bran oil, almond oil, jojoba oil, animal oil such as mink oil and turtle oil, cetanol, stearyl alcohol, cetostearyl alcohol Higher alcohols such as oleyl alcohol, octyldodecanol and behenyl alcohol, higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linoleic acid and isostearic acid, dimethyl silicone, methylphenyl silicone , Silicone oils such as cyclic silicone, etc. are oil phase components that have been widely used in the fields of cosmetics, quasi drugs, toiletry products, etc., and two or more kinds of these substances can be used in combination. The external preparation for skin of the present invention includes a nonionic surfactant, an anionic surfactant, a cationic surfactant, which are conventionally used depending on the purpose of use.
Amphoteric surfactant, lecithin, casein, sodium caseinate, synthetic or natural surfactant such as saponin or medicinal substance, ultraviolet absorber, antiseptic bactericide, antioxidant,
Various general-purpose additives such as a flavoring agent, a coloring agent, a thickener, and a stabilizer may be appropriately added within a range not impairing the object of the present invention.

In the present invention, S acid ester or its salt or O
Acid esters or salts thereof are emulsifiers, moisturizers,
It is effective as an emollient and a feeling-of-use improver, and may contain at least one of these four components. The amount thereof is not particularly limited, but usually 0.1 to 30.0% by weight may be used. Further, in order to mix with the water phase component, the oil phase component and other additives to produce a uniform dispersion, mixing and stirring may be carried out by a conventionally widely used method such as a homogenizer.

Sample 1 shown in Table 1, that is, glycerin ester of S acid (molar ratio 1: 1) was adjusted to pH value 6.0 with sodium hydroxide.
A skin irritation test was conducted on 20 healthy female adults using the 0.5% aqueous solution prepared above. When purified water was used as a control sample at this time and judged in accordance with Japanese standards, no skin irritation was observed as with the purified water of the control sample. Therefore, it can be said that this compound has extremely high skin safety.

[Action]

Esters of 4,5-dicapoxy-4-pentadecanolide and polyhydroxy compounds and salts thereof, and lactone ring of 4,5-dicarboxy-4-pentadecanolide opened at 3
-Hydroxy-1,3,4-tetradecanetricarboxylic acid ester of polyhydroxy compound and its salt are polybasic acid type surfactants, and ester type nonionic surfactant composed of higher fatty acid and polyhydroxy compound But also. The polybasic acid type surfactant, when used after being appropriately neutralized, also acts as a weakly acidic anionic surfactant, and as a result, it acts as a complex surfactant and becomes an aqueous phase component and an oil phase component. Any of these can be easily emulsified.

〔Example〕

In the examples and comparative examples, all parts by weight are parts by weight.

Example 1: Phase I cetanol 2.0 (part) Isopropyl palmitate 3.0 Squalane 7.0 Phase II Glycerin S 2.0 ter with a molar ratio of S acid 1: 2 (Sample 4) Glycerin 5.0 1,3-butylene glycol 2.0 Sodium hydroxide ( 50% aqueous solution) 0.3 Xanthan gum 0.2 (part) Methyl paraoxybenzoate 0.2 Purified water 78.3 Phase I, which is the oil phase component above, is heated to about 75 ° C to dissolve it uniformly, and Phase II is also heated to about 75 ° C. And dissolve evenly,
The solution of phase I was added to this while stirring with a homomixer to emulsify, and then cooled to 30 ° C. with stirring to obtain an emulsion. Observe the state of the obtained emulsion, pH at 25 ℃
Value, viscosity (cp), particle size (μm) and 7 at 45 ° C
The emulsion stability after day was determined. The results are shown in Table 2. Furthermore, the moisturizing properties of the obtained emulsion (shitsuto Sensitivity test) and usability (spreadability) were conducted by 20 adult females, and a “clear effect” was given.
The "slightly effective" was set to 1 and the "no effect" was set to 0, and the evaluation scores of all were summed, and the effectiveness% was calculated from the following formula.

Effectiveness (%) = (total score / 40) × 100 The results of this sensory test are summarized in Table 3. In the table, the numbers in parentheses indicate total evaluation points, and the numbers in parentheses indicate effectiveness.

Comparative Example 1: Instead of the S acid ester (Sample 4) in Example 1,
An emulsion was obtained in the same manner as in Example 1 except that steannic acid was used. The obtained emulsion was measured in the same manner as in Example 1, and the results are also shown in Table 2.

As is clear from Table 2, the emulsion of Example 1 was weakly acidic, the particle size was much smaller than that of the emulsion obtained in Comparative Example 1, and the stability after 7 days was also very good. It is also apparent from Table 3 that the emulsion of Example 1 is superior to the emulsion of Comparative Example 1 in both moisturizing properties and feeling of use.

Example 2: Phase I Squalane 13.0 (parts) Jojoba oil 2.0 Octyldodecyl myristate 5.0 Salix beeswax 2.0 Behenyl alcohol 3.0 Stearic acid 6.0 Phase II Glycerin 4.0 ester with a 1: 1 molar ratio of S acid (Sample 3) Glycerin 15.0 Hydroxylated Sodium (50% aqueous solution) 0.7 (parts) ε-aminocaproic acid 0.1 Purified water 48.9 Phase III aqueous solution Collagen 0.1 Yokuinin extract 0.1 Chamomile extract 0.1 Phase I oil phase component heated to approximately 75 ° C and uniformly dissolved Is heated by heating the phase II to about 75 ℃, mixed and stirred in a liquid that is homogeneously dissolved to emulsify and then cooled while stirring, and the mixed solution of the phase III is added at about 50 ℃, The temperature was lowered to ℃ and the stirring was stopped to obtain a skin cream. This skin cream had a pH value of 4.77 and had excellent emollient properties and moisturizing properties when applied to the skin, was stable, and had an extremely good feeling in use.

Example 3: Phase I Salix beeswax 5.0 (part) Cetanol 2.0 Vaseline 5.0 (part) Liquid paraffin (# 70) 30.0 Octyldodecyl myristate 5.0 Propyl paraoxybenzoate 0.2 Phase II Glycerin es 3.0 with a 1: 1 molar ratio of S acid. O-ester Glycerin 8.0 1,3-butylene glycol 4.0 ε-aminocaproic acid 0.1 Sodium hydroxide (50% aqueous solution) 0.5 Xanthan gum 0.1 Purified water 36.9 Phase III chamomile extract 0.1 Yokuinin extract 0.1 A cleansing olme was obtained by the same procedure as in Example 2 except that the ingredients of Phase I, Phase II and Phase III were different.
The cleansing cream had a pH value of 5.43 and did not turn white when applied to the skin, was stable and had an excellent feeling of use.

Example 4: Phase I Methyl paraoxybenzoate 0.2 (part) Glycerin 3.0 ester with a 1: 1 molar ratio of S acid (Sample 2 above) Propylene glycol 3.0 Ethanol 15.0 Sodium hydroxide (50% aqueous solution) 0.4 Phase II Epsilon-aminocapron Acid 0.2 Purified water 78.2 First, phase I was uniformly mixed and dissolved, and phase II, which had been uniformly dissolved in advance, was added thereto to obtain a transparent lotion for cleaning. The lotion for cleaning had a pH value of 5.82, which had a sufficient cleaning action and a moisturizing property, and was safe and had a good feeling in use.

Example 5: Phase I Diglycerin 3.0 (part) having a 1: 1 molar ratio of S acid Ester (Sample 7) Ethanol 75.0 Sodium hydroxide (50% aqueous solution) 0.3 Perfume 0.2 l-Menthol 0.2 Phase II Dye Qualified water Remaining total amount First, phase I was uniformly dissolved, and phase II was added thereto with stirring to obtain a uniform transparent hair nick. This hair nick imparted moderate emollient and moisturizing properties to the scalp, and was stable and had a good feeling in use.

Example 6: Phase I Diglycerin 5.0 ester with 1: 1 molar ratio of S acid (Sample 6 above) White petrolatum 25.0 Stearyl alcohol 20.0 Propylene glycol 12.0 (parts) Ethyl paraoxybenzoate 0.1 Propyl paraoxybenzoate 0.1 Phase II Purified water 37.8 In accordance with the eleventh revised Japanese Pharmacopoeia manufacturing method of hydrophilic ointment, first I
After the oil phase component of the phase was heated to about 75 ° C. to dissolve it uniformly, the Phase II component heated to the same temperature was added with stirring, mixed well and cooled to obtain a medicinal hydrophilic ointment. The pH value of this ointment is
Compared with polyoxyethylene hydrogenated castor oil 60, which is 3.47 and is used as an emulsifier in the Japanese Pharmacopoeia, there is no whiteness when applied to the skin, and the ointment is not inferior or superior in feeling when used. It was.

Example 7: Phase I Glycerin 2.0 (part) ester (molar ratio 1: 1) of S acid (Sample 3) Glycerin 15.0 Maltitol (75% aqueous solution) 15.0 Sodium hydroxide (50% aqueous solution) 0.3 (part) Phase II Squalane 50.0 Jojoba oil 17.5 Natural vitamin E acetate 0.3 Vitamin A palmitate 0.2 Methyl paraoxybenzoate 0.1 First, dissolve the phase I water phase component uniformly at room temperature, and add the phase II oil phase component while stirring to add sufficient After stirring to make the mixture uniform, the stirring was stopped to obtain a translucent oily jelly. The pH value of this jelly was 4.98, the viscosity at 25 ° C was 8700 cp, and the usability was good, and it was suitable as a beauty jelly.

〔effect〕

The external preparation for skin of the present invention described above is an ester of 4,5-dicarboxy-4-pentadecanolide and a polyhydroxy compound and a salt thereof, and 3-hydroxy-1,3,4-
An acidic region in which at least one of four components of an ester of tetradecanetricarboxylic acid and a polyhydroxy compound and a salt thereof is included, which exhibits both anionic and nonionic surface activity and which conventional soap emulsifiers cannot achieve. It is possible to say that the significance of the present invention is extremely great, because it enables emulsification in the present invention, and has a very excellent moisturizing effect and emollient effect as well as safety.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 9/107 B 47/14 H (56) References JP 62-30546 (JP, A)

Claims (4)

[Claims] 1. An ester of 4,5-dicarboxy-4-pentadecanolide and a polyhydroxy compound and a salt thereof, and 3-hydroxy-1,3 in which the lactone ring of 4,5-dicarboxy-4-pentadecanolide is opened. An external preparation for skin, comprising at least one component out of four components of an ester of 4,4-tetradecanetricarboxylic acid and a polyhydroxy compound and a salt thereof. 2. The external preparation for skin according to claim 1, wherein the polyhydroxy compound is at least one selected from glycerin, diglycerin, triglycerin and polyglycerin thereof. 3. A polyhydroxy compound is inositol, lactose, sucrose, glucose, fructose,
The external preparation for skin according to claim 1, which is at least one selected from sugars such as xylitol, mannitol, maltitol, sorbitol and pentaerythritol. 4. The polyhydroxy compound is ethylene glycol, propylene glycol, 1,3-butylene glycol,
The external preparation for skin according to claim 1, which is at least one selected from glycols such as 1,4-butylene glycol and hexylene glycol.