JPS63101308A - External drug for skin - Google Patents

Abstract

PURPOSE:To provide a high-quality external drug for skin containing an ester of 4,5-dicarboxy-4-pentadecanolide or 3-hydroxy-1,3,4-tetradecanetricarboxylic acid and a polyhydroxyl compound or its salt. CONSTITUTION:The objective external drug for skin contains at least one component selected from (A) an ester of 4,5-dicarboxy-4-pentadecanolide of formula and a polyhydroxyl compound, (B) its salt, (C) an ester of 3-hydroxy-1,3,4- tetradecanetricarboxylic acid (produced by opening the lactone ring of the compound of formula) and a polyhydroxyl compound and (D) its salt. The external drug exhibits both anionic and nonionic surface activities to enable the emulsification in acidic region. Furthermore, it has excellent moisture-retaining effect and emollient effect as well as high safety. The polyhydroxyl compound is e.g. polyglycerol, sugars, glycols, etc.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to an external skin preparation related to cosmetics, pharmaceuticals, quasi-drugs, toiletry products, and the like.

[Conventional technology]

In recent years, numerous studies have been conducted on emulsification, and new emulsifiers and emulsification technology have made remarkable progress. Emulsified compositions (emulsions) with very good stability have been developed and are now widely used in various fields as external preparations for the skin. It has come.

Conventionally, the characteristics that external skin preparations should have are (1)
Highly safe with no skin irritation (2) Stable and durable for long-term storage (3) Feels good during use and provides appropriate emollient properties (4) Provides appropriate moisturizing properties to the skin. However, even if the types of raw materials including surfactants are selected and the compositions are designed in order to express such characteristics, it is not easy to achieve this purpose.

For example, ether-type nonionic surfactants such as ethylene oxide adducts of higher aliphatic alcohols and higher fatty acid soaps that exhibit weak alkalinity generally have problems such as skin irritation, and they also contain higher fatty acids and polyhydroxy compounds. Ester-type nonionic surfactants have poor emulsifying properties, and external skin preparations that use higher fatty acid soaps as emulsifiers have the disadvantage that when applied to the skin, they have a large foaming property and the whiteness does not disappear forever. are doing.

[Problem that the invention seeks to solve]

As described above, the conventional technology has the problem that it is not possible to obtain an external preparation for skin that is satisfactory in terms of safety for the skin, emulsion stability, moisturizing properties, foaming properties, and feeling of use.

[Means for solving problems]

In order to solve the above-mentioned 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-opening method of 4.5-dicarboxy-4-pentadecanolide. The present invention employs means for producing an external skin preparation containing at least one acid component of the four components of esters of 3-hydroxy-1,3,4-tetradecanetricarboxylic acid and polyhydroxy compounds and salts thereof. The details will be described below.

First, 4,5-dicarboxy-4-pentadecanolide (also known as spicrisporic acid) in this invention.

S acid (hereinafter abbreviated as S acid) is a substance that is mass-produced in high yield as a metabolite of Penicillium spicrisporum through a microbial reaction using glucose as a raw material. Price: 336.
9. It is a substance with a saponification value of 515.1 and an iodine value of 0.5 or less.

Next, the polyhydroxy compound in this invention is a polyhydric alcohol having two or more hydroxyl groups in the molecule, such as glycerin, diglycerin, triglycerin or other polyglycerin, or inositol, lactose, sucrose, glucose, fructose, xylitol, mannitol, maltitol,
Sugars such as sorbitol and pentaerythritol, or ethylene glycol, propylene glycol, 1°3-
Examples include glycols such as butylene glycol, 1,4-butylene glycol, and hexylene glycol. In order to obtain spicrispole acid ester (hereinafter abbreviated as S acid ester) from such a polyhydroxy compound and the S acid, the dehydration reaction may be carried out at any molar ratio. 1 to 2 moles of glycerin, diglycerin (hydroxyl value 1300) or ethylene glycol as a polyhydroxy compound were charged into a reactor, and the reaction temperature was 110 to 170°C, the reaction pressure was 5.
When the dehydration reaction was carried out under reduced pressure of 9 mmHg or less or under normal pressure for a reaction time of 2 to 5 hours, S acid esters as shown in Table 1 were obtained. In addition, the viscosity in Table 1 is B
A - sign means that measurement was impossible due to high viscosity; surface tension was determined using a Wilhelmi set surface tension meter at 20°C, and foaming force was determined using the Ross Miles method. The % concentration, the value at 20°C, and the numbers in parentheses indicate the measured values after 5 minutes, respectively.

Furthermore, the ester of 3-hydroxy-1,3,4-tetradecanetricarboxylic acid (hereinafter referred to as 0 acid) and a polyhydroxy compound (hereinafter referred to as 0 acid ester) of the present invention is the S acid. The ester can be obtained by opening only the lactone ring under appropriate conditions, but the O acid and polyhydroxy compound obtained by adding excess sodium hydroxide aqueous solution to the S acid and neutralizing it with heated acid. It can also be obtained by dehydration reaction.

Furthermore, the respective salts of such S acid esters and O acid esters include, for example, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, magnesium salts, and other inorganic salts.

Salts with lysine, arginine, histidine, ornithine and other basic amino acids, basic oligopeptides containing these basic amino acids, salts with monoethanolamine, jetanolamine, triethanolamine and other basic amines, etc. These salts may be produced separately in advance, or may be produced during the manufacturing process of the external skin preparation.

The four components of the S-acid ester, O-acid ester, and their salts described above have a hydrophilic-lipophilic balance (HLB ) can be adjusted arbitrarily.

The emulsification 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 this invention are both polybasic acid type surfactants and ester type nonionic surfactants, the aqueous phase components and oil phase coexisting with them are It exhibits an excellent surfactant effect on both components.

Here, the aqueous phase components used in this invention are water, m alcohols such as ethanol, furopanol, impropatol, and phtanol, ethylene glycol, propylene glycol, 1.3-butylene glycol, and 1.4
- Butylene glycol, 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 cosmetics and pharmaceuticals. These are aqueous phase components that are already widely used in the fields of non-prescription products, pharmaceuticals, toiletry products, etc., and the use of two or more of these substances in combination will not impede the present invention.

In addition, the oil phase components used in this invention are liquid or semi-solid (such as liquid paraffin, squalane, and petrolatum).
Grease)-like hydrocarbons or octyldodecyl myristate, isopropyl palmitate, cetyl-2-ethylhexanoate, glyceryl-tri-2-ethylhexanoate, vitamin E acetate, vitamin A palmitate.

Ester oils such as vitamin C stearate, waxes such as solid paraffin, microcrystalline wax, ceresin wax, beeswax, spermaceti, olive oil, soybean oil, safflower oil, rice bran oil, almond oil,
Vegetable oils and fats such as jojoba oil, animal oils and fats such as mink oil and tardle oil, higher alcohols such as cetanol, stearyl alcohol, cetostearyl alcohol, oleyl alcohol, octyldodecanol, and behenyl alcohol, lauric acid, myristic acid, and palmitic acid. , higher fatty acids such as stearic acid, oleic acid, linoleic acid, lyluic acid, and instearic acid, silicone oils such as dimethyl silicone, methylphenyl silicone, and cyclic silicone, etc. Traditionally used in the fields of cosmetics, quasi-drugs, toiletry products, etc. These substances are widely used oil phase components, and two or more of these substances can also be used in combination. Depending on the purpose of use, the skin external preparation of this invention may contain conventionally used nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, lecithin, casein, sodium caseinate, The purpose of this invention is to use various general-purpose additives such as synthetic or natural surfactants or medicinal substances such as saponins, ultraviolet absorbers, preservatives, antioxidants, flavorings, colorants, thickeners, and stabilizers. may be added as appropriate within a range that does not inhibit.

In this invention, S acid ester or its salt or 0
Acid esters or their salts can be used as emulsifiers, humectants,
It is effective as an emollient and a feel improver, and it is sufficient to contain at least one of these four components, and the amount of the compound is not particularly limited, but is usually 0.1 to 30.0. In order to produce a homogeneous dispersion by mixing the aqueous phase component, oil phase component, and oil additive, a conventionally widely used method such as mixing and stirring using a homogenizer or the like may be used.

In addition, sample 1 shown in Table 1, that is, glycerin nis-til (molar ratio 1:1) of S acid, was adjusted to pH with sodium hydroxide.
A skin irritation test was conducted on 20 healthy adult women using 0 and 5% aqueous solutions adjusted to a value of 6.0. When purified water was used as a control sample and evaluated according to Japanese standards, no skin irritation was observed, as was the case with the purified water control sample. Therefore, it can be said that this compound is extremely safe for the skin.

[Effect]

4. Esters of 5-dicarboxy-4-pentadecanolide and polyhydroxy compounds and salts thereof.

4. Ester of 3-hydroxy-1,3,4-tetradecanetricarboxylic acid with opened lactone ring of 5-dicarboxy-4-pentadecanolide and polyhydroxy compound and its salt are polybasic acid type surfactants. It is also an ester type nonionic surfactant consisting of a higher fatty acid and a polyhydroxylated metal. Polybasic acid type surfactants can also act as weakly acidic anionic surfactants when used after being moderately neutralized, so they can act as composite surfactants and separate water phase components and oil phase components. Both can be easily emulsified.

[Example] All parts of the blending ratio in Examples and Comparative Examples are parts by weight.

Example 1: 1 phase cetanol 2.0 (parts) isopropyl palmitate 3.0 squalane
7.0 ■ Glycerin varnish with phase S acid molar ratio 1:2 2.0 chill (
Sample 4) Glycerin 5.0 1.3-Butylene glycol 2.0 Sodium hydroxide (5
0% aqueous solution) 0.3 xanthan gum
0.2 (parts) Methyl paraoxybenzoate 0.2 Purified water 78.3 Heat the above oil phase component (■) phase to about 75°C to uniformly dissolve it, and
The phase was similarly heated to 75°C to uniformly dissolve it, and the solution of phase 2 was added to this while stirring with a homomixer to emulsify it, and then cooled to 30°C while stirring to obtain a milky lotion.

Observe the state of the obtained emulsion and check the pH value at 25°C,
Viscosity (cp), particle size (μm) and 7 at 45°C
The emulsion stability after several days was determined. The results are shown in Table 2. Furthermore, a sensory test was conducted by 20 adult women regarding the moisturizing properties (moist second surface feeling) and feeling of use (spreadability) of the obtained emulsion, and the results were rated as ``clearly effective'' with 2,
The evaluation scores of all participants were summed, with ``somewhat effective'' being 1 and ``not effective'' being 0, and the effectiveness was calculated using the following formula.

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

Table 3 Comparative Example 1: Instead of the S acid ester (sample 4) in Example 1,
A milky lotion was obtained in the same manner as in Example 1 except that stearic acid was used. The obtained milky lotion was subjected to the same measurements as in Example 1, and the results are also listed in Table 2.

As is clear from Table 2, the emulsion of Example 1 was weakly acidic, had a much smaller particle size than the emulsion obtained in Comparative Example 1, and had very good stability after 7 days. Furthermore, from Table 3, it is clear 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 squalane 13.0 (parts) Jojoba oil 2.0 Octyldodecyl myristate 5.0 White beeswax
2.0 behenyl alcohol
3.0 stearic acid 6.0 ■
Glycerin 4.0 ester in a 1:1 molar ratio of Phase S acids (Sample 3 above) Glycerin 15.0 Sodium hydroxide (50% aqueous solution) 0.7 (parts) C-aminocaproic acid 0.1 Purified water
48.9■ Phase water-soluble collagen 0.1 Yokuinin extract 0.1 Chamomile extract
A liquid in which the oil phase components of the 0.1 phase were heated to about 75°C and uniformly dissolved was added and mixed with stirring to a liquid in which phase ① was heated to about 75°C and uniformly dissolved, and emulsified. After that, the mixture was cooled while stirring, and the mixed solution of phase (1) was added at about 50°C, and the temperature was lowered to 40°C and stirring was stopped to obtain a skin cream. This skin cream had a pH value of 4.77, had excellent emollient properties and moisturizing properties when applied to the skin, was stable, and had an extremely good feeling on use.

Example 3: ■Size beeswax 5.0 (parts) Setanol 2.0 Vaseline
5.0 (parts) liquid paraffin ($
70) 30.0 octyl dodecyl myristate 5.0 Propyl roseoxybenzoate 0.2 ■ Glycerin varnish with phase S acid molar ratio 1:1 3.0 Til (
O-acid ester glycerin with the lactone ring of sample 1) opened 8.01.3-Butylene glycol 4.0ε-Aminocaproic acid
0.1 Sodium hydroxide (50X aqueous solution)
0.5 xanthan gum 0.1
Purified water 36.9■ Phase Chamomile extract 0.1 Yokuinin extract 0.1 A cleansing cream was obtained through the same procedure as in Example 2 except that the ingredients of the phase, ■ phase, and ■ phase were different. This cleansing cream had a pH value of 5.43, did not turn white when applied to the skin, was stable, and had an excellent feeling of use.

Example 4: 1-phase bulk methyl oxybenzoate 0.2 (parts)
Glycerin 3.0 ester in a 1:1 molar ratio of S acid (sample 2) Propylene glycol 3.0 Ethanol 15.0 Sodium hydroxide (50% aqueous solution) 0.4 ■ Phase C-Aminocaproic acid 0.2 purified water
78.2 First, phase 1 was uniformly mixed and dissolved, and phase 2, which had been uniformly dissolved in advance, was added thereto to obtain a transparent cleansing lotion. The pH value of this cleaning lotion is 5.
82, had sufficient cleaning action and moisturizing properties, was safe, and had a good feeling of use.

Example 5: 3.0 parts of diglycerin in a 1:1 molar ratio of Phase I S acid
Ester (sample 7) Ethanol 75.0 Sodium hydroxide (50% aqueous solution) 0.3 Flavor
0.21-menthol
0.2 ■ Phase pigment Appropriate amount of purified water
First, phase 1 was uniformly dissolved, and phase 2 was added thereto with stirring to obtain a uniform and transparent hair tonic.

This hair tonic provided appropriate emollient and moisturizing properties to the scalp, and was stable and comfortable to use.

Example 6: Diglycerin 5.0 ester with a 1:1 molar ratio of S acid (sample 6) White petrolatum 25.0 Stearin alcohol 20.0 Propylene glycol 12.0 (parts) Ethyl roseoxybenzoate 0. 1-propyl paraoxybenzoate
0.1 ■Phase purified water 37.8 According to the 10th revised Japanese Pharmacopoeia hydrophilic ointment manufacturing method.

First, the oil phase component of phase 1 was heated to about 75° C. to uniformly dissolve it, then the phase 2 component heated to the same temperature was added with stirring, thoroughly mixed, and then cooled to obtain a medicated hydrophilic ointment. The pH value of this ointment is 3.47, and it is made from polyoxyethylene hydrogenated castor oil, which is used as an emulsifier in the Japanese Pharmacopoeia.
When compared with No. 0, the ointment did not appear white when applied to the skin and had a good feel when used, making it a comparable ointment.

Example 7: 2.0 parts of glycerin in a 1:1 molar ratio of S acid
Ester (sample 3) Glycerin 15.0 Maltitol (75% aqueous solution) IS, O Sodium hydroxide (
50% aqueous solution) (13 (parts) ■Phase squalane 50.O jojoba oil
17.5 Natural Vitamin E Acetate 0.3 Vitamin A Palmitate
0.2 Methyl paraoxybenzoate
0.1 First, the aqueous phase components of phase 1 are uniformly dissolved at room temperature,
The oil phase component of phase (1) was added to this without stirring, and the mixture was thoroughly stirred to make it homogeneous.The stirring was then stopped to obtain a translucent oily jelly. This jelly had a pH value of 4.98, a viscosity of 8,700 Cp at 25°C, and a good feeling of use, making it suitable as a cosmetic jelly.

〔effect〕

The skin external preparation of the present invention described above includes esters of 4,5-dicarboxy-4-pentadecanolide and polyhydroxy compounds and salts thereof, and 3-hydroxy-1,3
, an ester of 4-tetradecanetricarboxylic acid and a polyhydroxy compound, and a salt thereof, and exhibits both anionic and nonionic surface activity, which conventional soap emulsifiers cannot achieve. Enables emulsification in acidic areas, providing safety and moisturizing effect.
Since the emollient effect is also extremely good, it can be said that the significance of this invention is very great.

Claims (1)

[Claims] Esters of 1,4,5-dicarboxy-4-pentadecanolide and polyhydroxy compounds and salts thereof, and 3-hydroxy-opened lactone rings of 4,5-dicarboxy-4-pentadecanolide. 1. A skin external preparation comprising at least one of four components: an ester of 1,3,4-tetradecanetricarboxylic acid and a polyhydroxy compound and a salt thereof. 2. Claim 1, wherein the polyhydroxy compound is at least one selected from glycerin, diglycerin, triglycerin, and more polyglycerin.
External skin preparations as described in section. 3. The skin according to claim 1, wherein the polyhydroxy compound is at least one type of saccharide selected from saccharides such as inositol, lactose, saccharose, glucose, fructose, xylitol, mannitol, maltitol, sorbitol, and pentaerythritol. Topical preparation. 4. The polyhydroxy compound is ethylene glycol, propylene glycol, 1,3-butylene glycol, 1,
The skin external preparation according to claim 1, which is at least one kind selected from glycols such as 4-butylene glycol and hexylene glycol.