JPS6330882B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a radiation protective agent (hereinafter referred to as a sunscreen), and more particularly to a novel sunscreen useful for preventing sunburn on the skin.

The present invention discloses the use of benzalphthalides as a sunscreen agent, and the present invention discloses a sunscreen agent (composition) for protecting skin from ultraviolet radiation of sunlight, which comprises at least one benzalphthalide. ) and a skin protection method using the same.

Benzulfthalides, i.e. benzalphthalide and substituted benzalphthalides, obtained by reacting substituted or unsubstituted phthalic anhydride with substituted or unsubstituted phenylacetic acid, can effectively screen broad spectrum sunlight and are therefore used as sunscreen agents. It has been found that it has various uses.

Extensive research has been conducted on the ultraviolet radiation of sunlight and skylights reaching the earth's surface and its effects on the human skin. Radiation between 290 and 315 nanometers (nm) causes virtually all types of sunburn, emitting erythematous energy and a substantial portion of tanning energy; radiation between 315 and 400 nm incidentally promotes tanning. It has been proven that The different intensities of these various wavelength ranges and the erythema and tanning effects of tanning have been investigated, and methods have been established to accurately measure the effects of ultraviolet rays on normal, untanned skin.

Approximately 76% of the physiological tanning function of sunlight is
It exists in the ultraviolet rays in the wavelength range of 290 to 315 nm (so-called erythema region), and the rest of its function is in the wavelength range of 315 to 400 nm.
Ultraviolet rays in the wavelength range of m (so-called yellow-brown tanning range)
It has been found that there are Limiting the erythema of the skin necessarily limits the amount of sunburn that may occur due to UV radiation in the erythematous area, but since the tanned area does not have an erythematous effect, UV tanning in the tanned area will occur. There are no limits to the possibilities.

It is becoming increasingly clear that UV radiation on tanned skin areas has deleterious effects in terms of skin damage. There is therefore a need to develop spectral range sunscreens that have a wide range of effects.

Sunscreens for human applications are used by incorporating them into various cosmetic carriers, such as oil solutions, oil lotions or creams. In addition, artificial yellow-brown tanning, which gives a skin pigment that looks similar to natural melanin pigment,
Cosmetic vehicles can be formulated with substances such as dihydroxyacetone.

Therefore, UV (or sun) screening agents that are suitable for practically all purposes are those that (1) have a high screening effect, and (2) are readily available in various oily and alcoholic vehicles for use on human skin. can be combined,
and (3) remain safe, useful, and cosmetically acceptable under all conditions reasonably compatible with commercial use; and (3) in all cases of cosmetic application, storage, and use. It should be resistant to the oxidizing effects of air under conditions of 200 to 3000 ms and stable when exposed to both ultraviolet and visible radiation.

As a result of various studies, the present inventors have found that benzalphthalides, namely benzalphthalide and substituted benzalphthalides, are sunscreen agents that meet the above requirements and have very effective shielding properties against sunlight over a wide spectrum. They discovered this and completed the present invention.

Compounds useful in the present invention have the formula: [Wherein, X is a group selected from hydrogen, methyl, methoxy and halogen (preferably chloro),
Y represents a group selected from hydrogen and methyl.
X and Y may be the same or different. ] These are benzalphthalides represented by these, that is, benzalphthalide and substituted benzalphthalides.

The efficacy of X-substituted benzalphthalides is determined by empirical methods. For example, 4-nitrobenzulfthalide derivatives are ineffective, and 4-amino and 4-dimethylamino derivatives are unsatisfactory as cosmetic sunscreens. If the position of the substituent is shifted to one side, the preferable effect decreases, so conversely speaking, the position of the substituent is shifted to the position (4) shown in the above general formula.
(position) is particularly useful and important (however, the X substituent is not limited to this position, but may be at any substitutable position).

Y may be in any of the 3rd to 6th positions. When phthalic anhydride is reacted as an asymmetric anhydride with unsubstituted or substituted phenylacetic acid, a mixture of isomers is obtained. Although it is possible to separate one compound of these mixtures in the laboratory, in practice the mixtures do not have to be separated and can be used as a whole.

Particularly preferred compounds [] are 4-chlorobenzalphthalide, 4-methylbenzalphthalide, 3
-methoxybenzalphthalide, benzal-3-methylphthalide, 3-methoxybenzal-3-methylphthalide, and the like.

Benzulfthalides [ ] can generally be prepared from substituted or unsubstituted phthalic anhydride and the corresponding substituted or unsubstituted phenylacetic acid using sodium acetate, which is convenient as a catalyst.

Cosmetic oil carriers for use in the present invention may be those known in the trade, such as mineral oils, vegetable oils, animal oils, and isopropyl myristate.
The active benzalphthalides are preferably used in amounts sufficient to provide convenient sunscreen protection without exceeding solubility limitations in the carrier as described above. The typical range of benzalphthalides used in the carrier is about 1 to 8% by weight.
(usually about 1 to 5% by weight).

EXAMPLES Examples will be given below to clarify the method for producing the active compound of the present invention and its properties.

Example 1 Benzalphthalide: - 400 g of phthalic anhydride, 440 g of phenyl acetic acid and 5.2 g of sodium acetate (molten) were added to a water collector,
Comes with thermometer, nitrogen inlet and mechanical stirrer
Heat in a 2000ml flask. Heat for 1 hour at a temperature not exceeding 240°C, then for a further 2 hours at this temperature.
Collect 42 ml of water during heating. After cooling this to 90℃, slowly add 1000ml of ethanol and heat it again. After refluxing for 30 minutes, the solution is cooled below the reflux temperature, transferred to a 1000 ml beaker, and chilled overnight to allow crystallization.

After filtration and drying, 389 g of a yellow product was obtained. Perform the second crystallization from 1000ml of ethanol,
261 g of a very bright yellow product containing 2% carbon are obtained. Melting point 99-100℃.

Ultraviolet absorption spectrum data of benzalphthalide (isopropanol solvent): λmax=295nm, K=101.6; λmax=308nm,
K=94.2; λmax=340nm, K=94.4.

Sunscreen effect (transmittance to radiation in the wavelength range that causes erythema and yellow-brown sunburn): Concentration erythema transmittance Yellow-brown tan transmittance 1% 11.7% 19.7% 3% 0.2% 2.8% 4% 0.002% 1.6% Example 2 4-chlorobenzalphthalide: - 20.5 g (0.12 mol) of 4-chlorophenyl acetic acid,
A mixture of 14.8 g (0.1 mol) of phthalic anhydride and 0.2 g of molten sodium acetate is heated at 240° C. for 3 hours. During this time, collect 1.5 ml of water. Solution at 85℃
Cool and add to 500ml of isopropanol. After crystallization, the solid was removed and recrystallized from 300 ml of isopropanol to give a bright yellow product.
16.7g (65%) was obtained. Melting point: 138℃.

Ultraviolet absorption spectrum data of 4-chlorobenzalphthalide (chloroform solvent): λmax=298nm, K=249; λmax=311nm, K
=257; λmax=340nm, K=303.

Sunscreen effect (transmittance to radiation in the wavelength range that causes erythema and yellow-brown sunburn): Concentration Erythema transmittance Yellow-brown tan transmittance 3% 0.39% 1.13% Example 3 3-methoxybenzalphthalide: - 3-methoxy Phenyl acetic acid 20.0g (0.12mol),
14.8 g (0.1 mol) of phthalic anhydride and 0.2 g of molten sodium acetate are heated to 230-240 DEG C. and held at this temperature for 3 hours. During this time, 1.7 ml of water is collected in the collector. Cool the mixture to 90°C and add to 500 ml of isopropanol. After cooling to room temperature,
Take the crystal. Add this to 500ml of isopropanol
A very bright yellow solid product recrystallized from
17.1g (69%) was obtained. Melting point: 138℃.

Ultraviolet absorption spectrum data of 3-methoxybenzalphthalide (chloroform solvent): λmax=300nm, K=218; λmax=343nm, K
=244.

Sunscreen effect (transmittance to radiation in the wavelength range that causes erythema and yellow-brown sunburn): Concentration Erythema transmittance Yellow-brown tan transmittance 3% 0.79% 1.31% Example 4 4-Methylbenzalphthalide: -4-methylphenyl After heating 10 g (0.067 mol) of acetic acid, 12.3 g (0.083 mol) of phthalic anhydride and 0.2 g of molten sodium acetate at 240°C for 3 hours,
Collect 1.2 ml of water in the collector. Cool the mixture to 90 °C and pour into 500 ml of isopropanol. Separate the solid under reduced pressure and add this to 300 ml of hot isopropanol.
Recrystallization from 11.4 g (72%) of a yellow product was obtained. Melting point: 123℃.

Ultraviolet absorption spectrum data of 4-methylbenzalphthalide (chloroform solvent): λmax = 301 nm, K = 224; λmax = 312 nm, K
= 228; λmax = 344 nm, K = 264.

Sunscreen effect (transmittance to radiation in the wavelength range that causes erythema and yellow-brown tanning): Concentration Erythema transmittance Yellow-brown tanning transmittance 3% 0.67% 0.82% Example 5 Benzal-3-methylphthalide: - Phenyl acetic acid 16.3 g, After heating 16.2 g of 3-methylphthalic anhydride and 0.2 g of molten sodium acetate at 250°C for 2 hours under a nitrogen atmosphere, the contents were
Cool to 75-80℃ and add to 100g of isopropanol. After this is brought to a boil, the solution is filtered and cooled to room temperature. After drying a small amount of precipitated material (2.1 g), the product was obtained (compound #1) with a melting point of about 360°C. The isopropanol solution was cooled in a dry ice bath to obtain a second product (4.2 g) with a melting point of 357° C. (Compound #2). After concentrating the volume of the isopropanol solution to about 1/10, a substance (0.2 g) with a melting point of 150° C. was obtained as a product (compound #3).

Ultraviolet absorption spectrum data of benzal-3-methylphthalide (isopropanol solvent): Compound #1...34.3nm, K=83; 308nm, K
=72; 294nm, K=75.6.

Compound #2...343nm, K=89; 308nm, K
=80; 294nm, K=88.

Compound #3...343nm, K=95.4; 308nm, K
=81.4; 294nm, K=83.4.

The structures of these three compounds were not elucidated. Commercially available compounds can include these three compounds.

Example 6 3-methoxybenzal-3-methylphthalide:
- As above, 3-methylphthalic anhydride and 3-
The title compound was obtained from methoxyphenyl acetic acid. The ultraviolet absorption spectrum was determined as a mixture without separating the isomers.

Ultraviolet absorption spectrum data of 3-methoxybenzal-3-methylphthalide (isopropanol solvent): λmax = 293nm, K = 67.0: λmax = 303n
m, K=64.3; λmax=347nm, K=78.5.

The shielding effect of a sunscreen agent can be calculated by dividing the absorption amount at the maximum peak between 290 and 315 nm by the concentration (g/). This value is known as the K value of the sunscreen. The higher the K value, the greater the sunscreening ability; the lower the K value, the greater the amount of screening agent required to protect from the erythematous rays of sunlight. In other words, in the production of a cosmetically acceptable sunscreen composition,
The K value can be utilized to determine the amount of sunscreen active material required to protect from solar ultraviolet radiation.

The above examples demonstrate that the active agents of the present invention are particularly useful broad-spectrum sunlight screening agents, even in small amounts.

When considering the activity of each of the compounds of Examples 2 to 4, it is significant that the position of the substituent is important.

A mixture of the active compounds in the present invention can be used if necessary. The advantages of the present invention are obvious from a technical point of view in the field, and the sunscreen agent of the present invention can provide an improved and novel sunscreen effect that is more useful for blocking a broad spectrum of eye light. .

It should be understood that the present invention is not limited to the specific embodiments described as particularly preferred embodiments, but that various improvements and modifications may be applied without departing from the technical scope thereof. It won't happen.

As mentioned above, the present invention can provide a method of protecting human skin from sunburn. In order to further clarify such uses, preferred skin protection methods of the present invention are listed below.

(1) Formula contained in the carrier [] [In the formula, X represents hydrogen, methyl, methoxy or halogen, and Y represents hydrogen or methyl. ]
A method for protecting human skin from the radiation effects of sunlight that induces erythema and yellow-brown sunburn, the method comprising applying benzalphthalides represented by:

(2) The method according to (1) above, wherein benzalphthalides are dispersed and contained in a cosmetic oil carrier in an amount ranging from an effective amount for protection to an amount at the limit of solubility.

(3) The above, wherein the benzalphthalide is 4-chlorobenzalphthalide, 4-methylbenzalphthalide, 3-methoxybenzalphthalide, benzal-3-methylphthalide, 3-methoxybenzal-3-methylphthalide or benzalphthalide.
(1) The method described.

(4) The method described in (1) above using the active substance of any of Examples 1 to 6.

Claims (1)

[Claims] 1. As an active ingredient, the formula [] [In the formula, X represents hydrogen, methyl, methoxy or halogen, and Y represents hydrogen or methyl. ] A protective agent against radiation that causes erythema and yellowish brown sunburn, containing a compound represented by the following. 2. The protective agent according to claim 1, which contains the active ingredient dispersed in a cosmetic oil carrier in an amount ranging from an effective amount for protection to an amount at the limit of solubility. 3 The compound represented by formula [] is 4-chlorobenzalphthalide, 4-methylbenzalphthalide, 3
The protective agent according to claim 1, which is -methoxybenzalphthalide, benzal-3-methylphthalide, 3-methoxybenzal-3-methylphthalide, or benzalphthalide.