JPH04305592A - Saccharide cinnamic acid derivative and ultraviolet light absorber - Google Patents

Abstract

PURPOSE:To obtain a new saccharide cinnamic acid derivative useful as a water-soluble ultraviolet light absorber because of water solubility and excellent absorption of ultraviolet rays of middle wavelength and excellent in chemical stability, oxidation stability, safety and moisture retention. CONSTITUTION:A compound shown by formula I (A is residue obtained after removal of n hydroxyl groups from saccharide or sugaralcohol; X is alkoxy; a is 1-3; n is integer) such as maltitol monotrimethoxycinnamic ester. The compound, for example, is obtained by dissolving a saccharide in a nonaqueous solvent such as DMF and subjecting the saccharide and a compound shown by formula II (R is lower alkyl) to transesterification in the presence of a catalyst at 50-130 deg.C under stirring. The molar ratio of the saccharide to the compound shown by formula II, for example in the case of production of a monoester as a main product, is preferably 2-3:1.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to sugar cinnamic acid derivatives and ultraviolet absorbers, and more particularly to water-soluble sugar cinnamic acid derivatives having ultraviolet absorbing properties and ultraviolet absorbers using the same.

0002

[Prior Art] The ultraviolet rays contained in sunlight are 400n
m~320nm long wavelength ultraviolet (UV-A), 320n
Medium wavelength ultraviolet light (UV-B) from m to 280nm, 280n
It is classified as short wavelength ultraviolet light (UV-C) with wavelengths below m. Among these, ultraviolet rays with a wavelength of 290 nm or less are absorbed by the ozone layer and do not reach the earth's surface.

Since ultraviolet rays that reach the earth's surface strongly induce chemical reactions, attempts have been made to incorporate ultraviolet absorbers into various paints, coatings, and the like. On the other hand, ultraviolet rays have various effects on human skin. Although UV-A causes problems such as primary darkening, the effects of UV-B are particularly severe. Accelerated formation causes problems such as pigmentation, and in the long term it accelerates skin aging and causes skin cancer.

[0004] Various types of ultraviolet absorbers have been developed to eliminate the effects of ultraviolet rays. As existing ultraviolet absorbers, PABA derivatives, cinnamic acid derivatives, salicylic acid derivatives, benzophenone derivatives, urocanic acid derivatives, camphor derivatives, heterocyclic derivatives, etc. are known.

[0005] These UV-B absorbers are incorporated into paints, coatings, cosmetics, pharmaceuticals, quasi-drugs, and other external skin preparations. For example, in the case of external skin preparations, they are A low molecular weight dimethylsiloxane base is widely used. That is, since sunscreens are most frequently used in summer, most of the UV absorbers that have been used from the viewpoint of sweat resistance, water resistance, etc. have been oil-soluble.

[0006]

[Problems to be Solved by the Invention] However, in recent years, the influence of ultraviolet rays in daily life has become a problem, and sunscreens are desired for normal skin care. For this reason, ■It is better to be able to incorporate large amounts of UV absorbers into water-based skin care products such as lotions, and ■When formulating external preparations with higher UV absorption effects, it is better to be able to incorporate large amounts of UV absorbers into the entire system. There has been a strong demand for the development of water-soluble ultraviolet absorbers from the viewpoint of the desire to incorporate ultraviolet absorbers not only in the oil phase but also in the aqueous phase.

However, as mentioned above, most conventional UV-B absorbers are oil-soluble and have low water solubility, which limits their formulation. As a water-soluble UV-B absorber, only 2
-Hydroxy-4-methoxy-5-sulfoxonium benzophenone sodium salt is only known, and since it is a salt, there is a problem that it affects the pH of the formulation system.

The present invention has been made in view of the problems of the prior art, and its purpose is to provide a sugar cinnamic acid derivative and an ultraviolet absorber that have excellent UV-B absorption properties and are water-soluble. There is a particular thing.

[0009]

[Means for Solving the Problems] In order to achieve the above object, the present inventors have made intensive studies and found that a sugar cinnamic acid derivative in which sugar is bonded to cinnamic acid has excellent UV-B absorption and water solubility. They discovered something and completed the present invention.

That is, the sugar cinnamic acid derivative according to claim 1 of the present application is characterized by being represented by the following general formula 2.

[Chemical formula 2] (In the formula, A is a residue obtained by removing n hydroxyl groups from a sugar or sugar alcohol, X is an alkoxy group, a is an integer from 1 to 3, and n is an integer)

[0011] Furthermore, the ultraviolet absorbent according to claim 2 of the present application is characterized by being represented by the above general formula 2.

The configuration of the present invention will be explained in more detail below. In general formula 2, specific examples of sugar A include glucose, galactose, xylose, fructose,
altrose, talose, mannose, arabinose,
Monosaccharides such as idose, lyxose, ribose, allose and mixtures thereof, or maltose, isomalsose,
Lactose, xylobiose, kenchibiose, cordiobiose, cellobiose, sophorose, nigerose,
Examples include disaccharides and mixtures thereof such as sucrose, melibiose, laminaribiose, and rutinose, and sugar alcohols and mixtures thereof such as maltitol, sorbitol, mannitol, galactitol, glucitol, and inositol. You can also do it. Further, a mixture of monosaccharides, disaccharides, sugar alcohols, and higher polysaccharides may be used.

Examples of X include methoxy, ethoxy, and isopropyl groups. Although there is no significant difference in water solubility and UV-B absorption wavelength, a methoxy group is particularly preferred from the viewpoint of industrial efficiency.

The sugar cinnamic acid derivative of the present invention can be prepared by transesterification (hot melt method, Schnell method, Nebraska-Schnell method, Zimmer method, Nebraska-DKS method, US Pat.
, 999,858 (1961), U.S. Patent No. 2,948
, No. 717 (1960), U.S. Patent No. 3,021,324
No. (1962), German Patent No. 1,098,501 (
1961), Japanese Patent No. 404,285 (1962), etc.), reaction with cinnamic acid anhydride, reaction with cinnamic acid chloride, etc., and can be synthesized by reactions generally used for esterification. For example, it can be synthesized by the Nebraska-Schnell method.

That is, sugar can be converted into dimethylformamide, dimethylsulfoxide, dioxane, dimethylacetamide,
N-methylpyrrolidone, N-acetylmorpholine, N-
Dissolved in a non-aqueous solvent such as methylsuccinimide, and added to the general formula 3:

[Formula 3] (wherein R is a lower alkyl group such as a methyl group or ethyl group, and X and a are the same as in Formula 2 above) is added, and in the presence of a catalyst, , 50-130
It is obtained by stirring and transesterifying at °C. At this time, the reaction is carried out under reduced pressure, and the compounds represented by the general formula 2 may be used alone or in combination of two or more.

The above catalysts include mineral acids such as sulfuric acid, alkalis such as lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium carbonate and sodium carbonate, sodium alcoholates such as sodium methylate and sodium ethylate, Examples include amines such as N-methylbenzylamine.

The molar ratio of the sugar used in this reaction to the compound represented by the general formula 3 is, for example, 1 to 3:1, more preferably 2 to 3:1, when monoester is to be obtained as the main product. It is 1. If there is too much sugar, a large amount of sugar will remain and interfere with subsequent purification.

When all the compounds represented by the general formula 3 are consumed, acids such as acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, lithium hydroxide, sodium hydroxide, hydroxide etc. are added for the purpose of neutralizing the catalyst in the reaction system. An alkali such as potassium is added, and the reaction solvent is distilled off under reduced pressure.

The reaction product thus obtained includes:
In addition to the sugar cinnamic acid derivative represented by the general formula 2, salts, sugars, etc. during neutralization coexist. Therefore, for example, when removing sugar and salt, extraction is performed with a solvent that does not dissolve sugar, such as methyl alcohol, ethyl alcohol, butyl alcohol, or isopropyl alcohol, or partitioning with water containing a large amount of salt and methyl ethyl ketone or n-butanol. Purification can be achieved by separating the organic solvent layer.

In addition, when removing sugars and salts and separating compounds according to the number of bonded ester groups, the reaction product is suspended in water or a mixture of water and alcohol, and a hyperporous polymer (for example, Mitsubishi Chemical Corporation) First, water is passed through a reversed-phase distribution column such as octadecyl silica (high porous resin manufactured by the company), and then a mixture of water and an alcohol such as methanol or ethanol or a polar organic solvent such as acetonitrile is passed through the column. Separation and purification can be achieved by fractionating this liquid. Others include the method of Snell et al.
1-6852, Japanese Patent Publication No. 40-26250, etc., or extraction and purification with acetone.

The sugar cinnamic acid derivative synthesized as described above is
It may be used after distilling off the extraction solvent or purifying with a column, or it may be used as it is.

The sugar cinnamic acid thus obtained is solid, has excellent chemical stability, oxidative stability, and safety, and is water-soluble.
In addition, it has absorption in the UV-B region and has excellent moisturizing properties.

The above sugar cinnamic acid derivatives can be used in paints, inks,
It can be blended into chemical products such as plastics, coating agents, and chemical fibers, and can also be blended as an ingredient in pharmaceuticals, quasi-drugs, cosmetics, and cleaning products. In addition to the sugar cinnamic acid derivative according to the present invention, other commonly used paints, coatings, cosmetics, and pharmaceutical ingredients can be appropriately blended.

For example, various hydrocarbons and fats and oils such as liquid paraffin, squalane, petrolatum, cetyl alcohol, isostearyl alcohol, cetyl 2-ethylhexanoate, 2-octyldodecyl alcohol, glyceryl triisostearate, macadamian nut oil, and lanolin. kind,
Oily components such as waxes, silicones, surfactants, thickeners, neutralizing agents, preservatives, bactericidal agents, antioxidants, powder components,
Pigments, fragrances, other UV absorbers, medicinal agents, sequestering agents,
Examples include pH adjusters.

[0025]

Effects of the Invention The sugar cinnamic acid derivative and ultraviolet absorber according to the present invention have excellent chemical stability and water solubility, and
Ultraviolet rays in the V-B region can be efficiently absorbed.

[0026]

[Examples] Next, the present invention will be explained in more detail with reference to test examples and examples. Note that the present invention is not limited to this. First, the method for producing sugar cinnamic acid according to the present invention will be explained.

Example 1 (Maltitol trimethoxine cinnamic acid ester) 15 g of trimethoxycinnamic acid was dissolved in HCl-
The solution was dissolved in 150 ml of MeOH solution, heated under reflux for 1 hour, and then concentrated under reduced pressure. Extract with 300ml of ethyl acetate,
After washing 5 times with 200 ml of purified water, the organic layer was dried over anhydrous magnesium sulfate, the crystals were filtered off, and then concentrated under reduced pressure. The obtained product was recrystallized from methanol to give trimethoxycinnamic acid methyl ester with a recrystallization yield of 97%.
5g was obtained.

[0028] 1.28 g of maltitol was dissolved in 5 ml of dimethyl sulfoxide that had been dried in advance, and 3 g of the synthesized trimethoxycinnamic acid methyl ester was added thereto. Then, 1.6 g of potassium carbonate was added under stirring, and then the mixture was dissolved under reduced pressure. 100
The mixture was heated and stirred at ℃ for 2 hours. After air-cooling the reaction system to room temperature, it was neutralized with hydrochloric acid.

The reaction solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography using hyperporous polymer (high porous resin manufactured by Mitsubishi Chemical Industries, Ltd.) using first purified water and then ethyl alcohol as the developing solvent. Purified water =
When fractionation was performed using a 7:3 ratio, potassium chloride, maltitol, and dimethyl sulfoxide were found in the purified water eluate, and the ethyl alcohol:purified water 7:3 eluate was concentrated.

The yield of maltitol monotrimethoxycinnamate ester was 2.01 g (yield 30.0%). Moreover, the obtained maltitol trimethoxy cinnamic acid ester was analyzed by the following methods (1) to (4). The thus obtained maltitol monotrimethoxycinnamic acid ester was designated as Sample 1.

(1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement device manufactured by JASCO Corporation, measurement was performed using the neat method, and the result was 3400 cm.
Absorption due to the stretching vibration of the hydroxyl group at −1, the stretching motion of the methoxy group at around 2900 cm −1 , and the stretching motion of the carbonyl group at 1690 cm −1 was observed. The results are shown in Figure 1.

(2) 13C-NMR measurement method CD3OD was measured using JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using as a solvent, it was 169-10
A signal originating from the trimethoxycinnamic acid moiety was observed at 2 ppm, and a signal originating from the carbon of the maltitol moiety was observed at 62 to 100 ppm. The results are shown in Figure 2.

(3) 1H-NMR measurement method When measured at room temperature using CD3OD as a solvent using JOEL GX-400 manufactured by JEOL Ltd., the result was 7.7 to 6.4.
A signal originating from the trimethoxycinnamic acid moiety was observed at ppm, and a signal originating from the hydrogen of the maltitol moiety was observed at 3.0 to 5.0 ppm. The results are shown in Figure 3.
Shown below.

(4) Ultraviolet Absorption Spectrum Measuring Method When measured using a UVIDEC 61OC ultraviolet absorption spectrometer manufactured by JASCO Corporation and using methanol as a solvent, maximum absorption was observed at around 230 nm and at 310 nm. The results are shown in Figure 4.

Example 2 (Sorbitol trimethoxycinnamate ester) 6.49 g of sorbitol was dissolved in 26 ml of previously dried dimethyl sulfoxide, and 3.0 g of the synthesized methyl ester trimethoxycinnamate was added, followed by stirring. 1.64 g of potassium carbonate was added to the bottom, and the mixture was heated and stirred under reduced pressure for 2 hours. After the reaction, the mixture was air cooled to room temperature and neutralized with hydrochloric acid.

[0036] Thereafter, the solvent was distilled off under reduced pressure, and the resulting residue was subjected to a column chromatograph method using hyperporous polymer (high porous resin manufactured by Mitsubishi Chemical Industries, Ltd.) using first purified water and then purified water as a developing solvent. When fractionation was performed using ethyl alcohol:purified water=1:1, potassium chloride, sorbitol, and dimethyl sulfoxide were found in the eluate of purified water, and the eluate of ethyl alcohol:purified water=1:1 was concentrated.

The yield of sorbitol monotrimethoxycinnamate ester was 8.6 g (yield 30.47%). The sorbitol monotrimethoxycinnamate ester thus obtained was analyzed by methods (1) to (4).

(1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement device manufactured by JASCO Corporation, measurement was performed using the neat method, and the result was 3400 cm.
Absorption due to the stretching vibration of the hydroxyl group at −1, the stretching motion of the methoxy group at around 2900 cm −1 , and the stretching motion of the carbonyl group at 1690 cm −1 was observed. The results are shown in Figure 5.

(2) 13C-NMR measurement method CD3OD was measured using JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using as a solvent, it was 169-10
A signal originating from the trimethoxycinnamic acid moiety was observed at 6 ppm, and a signal originating from the carbon of the maltitol moiety was observed at 62 to 100 ppm. The results are shown in FIG.

(3) 1H-NMR measurement method When measured at room temperature using CD3OD as a solvent using JOEL GX-400 manufactured by JEOL Ltd., 7.7 to 6.4p was measured.
The signal derived from the trimethoxycinnamic acid moiety in pm is
Further, signals derived from hydrogen in the maltitol moiety were observed at 3.0 to 5.0 ppm. The results are shown in FIG.

(4) Ultraviolet Absorption Spectrum Measuring Method When measured using a UVIDEC 61OC ultraviolet absorption spectrometer manufactured by JASCO Corporation and using methanol as a solvent, maximum absorption was observed at around 230 nm and around 310 nm. The results are shown in FIG.

The solubility of the sugar cinnamic acids in Examples 1 and 2 in water was 20% by weight or more.

Furthermore, the compounds obtained in Examples 1 and 2 were white solids. Due to high moisture absorption, it was not possible to measure the melting point.

Next, a skin preparation for external use containing the glycocinnamic acid derivative obtained as described above will be explained. first,
A test was conducted on the sunscreen effect of the skin external preparation according to the present invention.

Test Example Production of a serum containing a sugar cinnamic acid derivative and, as a control, a serum containing 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone in the formulation shown in Table 1 below. I did it.

[0046]

[Table 1] −−−−−−−−−−−−−−−−−−−−−
−−−−−−−−−−− Ingredients
Formulation example 1 Control example 1
−−−−−−−−−−−−−−−−−−−−−−−−−
--A. (Alcohol phase) Ethanol
5.0% 5.0
%POE oleyl alcohol ether 2.
0 2.0 fragrance

0.05 0.05B. (Aqueous phase) 1,3-butylene glycol
5.0 5.0 Maltitol trimethoxy cinnamic acid ester
7.0 -2-Hydroxy-4-methoxy-5-sulfoxonium phenone -
7.0 Triethanolamine
0.1 0.1
carboxyvinyl polymer
0.15 0.15 Purified water

Residual Residual -
−−−−−−−−−−−−−−−−−−−−−−−−−
−−−−−−−−−−

<Production method> The alcohol phase of A was added to the aqueous phase of B to solubilize the perfume to obtain a beauty serum. (2) Appearance Condition In Formulation Example 1, a colorless, transparent, and viscous beauty serum was obtained, whereas in the control example, the serum had a strong yellowish tinge and no viscosity. ■Sunscreen effect In an actual use test at the beach, two samples were applied to each half of a panel of 10 people, and a questionnaire survey on the degree of sunburn and a survey on skin problems were conducted. The results are shown in Table 2.

[0048]

[Table 2] −−−−−−−−−−−−−−−−−−−−−−−−
−−−−−−−−−−−
Formulation example 1 Control example 1
Sample application section Sample application section------
−−−−−−−−−−−−−−−−−−−−−−−−−
-------- Panel A
○ △
B ○
△
C △
×
D ○
×E
△
△F
△
× G
○
×H
○
△ I
○
△J
○
△−−−−−−−−−−−−−−−−−−−
−−−−−−−−−−−−−−−−−Number of skin problems None
2 cases of irritation

Itching 5 cases

3 cases of rash----------------------
−−−−−−−−−−−−−−−−−−−−Evaluation criteria for degree of sunburn Strong erythema was observed … × Slight erythema was observed … △ Erythema was not observed There wasn’t… ○

[0049] From these results, it was concluded that external skin preparations containing glycocinnamic acid derivatives have a higher UV protection effect than conventional skin preparations containing water-soluble ultraviolet absorbers, and are highly safe with no skin troubles. Ta.

Examples of formulations of compositions containing sugar cinnamic acid derivatives according to the present invention will be explained below. In addition, each of the skin external preparations showed excellent UV protection effects.

Formulation Example 2 Cream A. Oil phase stearic acid
10.0% stearyl alcohol
4.0 Stearic acid monoglycerol ester 8.
0 Vitamin E acetate
0.5 fragrance

0.4 Ethylparaben
0.1 Butylparaben
0.1 Propylparaben

0.1B. Aqueous phase Propylene glycol
8.0 Glycerin
2.0 Maltitol trimethoxy cinnamic acid ester 5.0
potassium hydroxide
0.4 Trisodium edetate
0.05 Purified water

Remains <Production method> The oil phase part of A and the aqueous phase part of B are heated to 70°C and completely dissolved. Add phase A to phase B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain cream.

Formulation Example 3 Cream A. Oil phase Setanol
4.0
Vaseline
7.0 Isopropyl myristate
8.0 Squalane

12.0 Dimethylpolysiloxane
3
．． 0 Stearic acid monoglycerin ester
2.2 POE (20) Sorbitan Monostearate
2.8 Glycyrrhetinic acid stearate BHT
0.02 Ethylparaben

0.1 Butylparaben

0.1B. Water phase 1.3 butylene glycol
7.0 Edetate disodium
0.07 Phenoxyethanol

0.2 L-ascorbic acid phosphate ester magnesium salt 3.0 Polyacrylic acid alkyl ester 1.0 Sorbitol trimethoxy cinnamate ester
7.0 Purified water

Residue <Production method> A cream was obtained according to Formulation Example 2.

Formulation Example 4 Emulsion A. Oil phase squalane
5.0
oleyl oleate
3.0 Vaseline

2.0 Sorbitan sesquioleate ester
0.8 Polyoxyethylene oleyl ether (20
E. O. ) 1.2 2-ethylhexyl-p-methoxycinnamate 3.0 Methylparaben
0.15 fragrance

0.12B. Aqueous phase dipropylene glycol
5.0 Ethanol

3.0 Carboxyvinyl polymer
0.17 Sodium hyaluronate
0.1
Maltitol trimethoxy cinnamic acid ester
4.0 Potassium hydroxide

0.08 Sodium hexametaphosphate
0.05 Purified water
Residue <Manufacturing method> A milky lotion was obtained according to Formulation Example 2.

Formulation Example 5 Cream A. Oil phase behenyl alcohol
0.5% 12-
Hydroxystearic acid cholestanol ester 2.
0 squalane
7.0
jojoba oil
5.0 Self-emulsifying glyceryl monostearate
2.5 Polyoxyethylene sorbitan monostearate (20EO)
1.5 2-hydroxy-4-methoxybenzophenone 3.0
ethylparaben
0.2 Butylparaben
0.1 Fragrance

0.1B. Aqueous phase Propylene glycol
5.0 Glycerin
5.0 Veegum (montmorillonite)
3.0 Potassium hydroxide
0.
3 Maltitol trimethoxy cinnamate ester
6.0 Trisodium edetate

0.08 <Production method> A cream was obtained according to Formulation Example 2.

Formulation Example 6 Powdered lotion A. Oil phase ethanol
8.0
POE (60) glyceryl monoisostearate
2.0 L-menthol
0.1
camphor
0.1
Methylparaben
0.1 Fragrance

0.03B. Aqueous phase glycerin
3.5
Sorbitol trimethoxy cinnamate ester
4.0 Zinc

1.5 Kaolin

0.5 bentonite

0.3 Sodium hexametaphosphate
0.03 Purified water
Residue <Production method>
A powdered lotion was obtained using a manufacturing method similar to Formulation Example 1.

[Brief explanation of the drawing]

FIG. 1 is an infrared absorption spectrum diagram of maltitol trimethoxy cinnamic acid ester according to the present invention.

FIG. 2 is a 13C-NMR diagram of maltitol trimethoxy cinnamic acid ester according to the present invention.

FIG. 3 is a 1H-NMR diagram of maltitol trimethoxy cinnamic acid ester according to the present invention.

FIG. 4 is an ultraviolet absorption spectrum diagram of maltitol trimethoxy cinnamic acid ester according to the present invention.

FIG. 5 is an infrared absorption spectrum diagram of sorbitol trimethoxycinnamate according to the present invention.

FIG. 6 is a 13C-NMR diagram of rubitol trimethoxy cinnamic acid ester according to the present invention.

FIG. 7: 1H-NMR diagram of sorbitol trimethoxy cinnamic acid ester according to the present invention,

FIG. 8 is an ultraviolet absorption spectrum diagram of sorbitol trimethoxycinnamate according to the present invention.

Claims (2)

[Claims] [Claim 1] A sugar cinnamic acid derivative represented by the following general formula 1. [Chemical formula 1] (In the formula, A is a residue obtained by removing n hydroxyl groups from a sugar or sugar alcohol, X is an alkoxy group, a is an integer from 1 to 3, and n is an integer) 2. A UV absorber comprising the sugar cinnamic acid derivative according to claim 1.