JP3534938B2 - Hydantoin derivatives, ultraviolet absorbers and skin external preparations - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel hydantoin derivative, an ultraviolet absorbent and an external preparation for skin, in particular a water-soluble hydantoin derivative having an ultraviolet absorption property, an ultraviolet absorbent using the same and an external skin preparation containing the same. Regarding agents.

[0002]

BACKGROUND OF THE INVENTION Ultraviolet light is known to cause various changes to the skin. Dermatological classification of ultraviolet rays is divided into long-wavelength ultraviolet rays of 400 to 320 nm called UV-A, medium wavelength ultraviolet rays of 320 to 290 nm called UV-B, and short wavelength ultraviolet rays of 290 nm or shorter called UV-C. Usually, most of the ultraviolet rays that humans are exposed to are sunlight, but the ultraviolet rays that reach the ground are UV-
In A and UV-B, UV-C is absorbed in the ozone layer and hardly reaches the ground. In the ultraviolet rays that reach the ground, UV-B causes erythema and blisters on the skin, and UV-A
Has been found to promote skin aging when it results in blackening of the skin and over time.

Although many UV-B absorbers have been developed in the past, UV-A has received much attention because it has been accepted as ultraviolet rays that make the skin a healthy wheat color at the seaside in summer. There wasn't. However, in recent years, UV-A absorbers have been attracting attention in view of increasing consumer demand for white skin throughout the four seasons and preventing skin aging.

As existing UV-A absorbers, benzophenone derivatives, dibenzoylmethane derivatives, benzotriazole derivatives and the like are known, and they have been used by being blended with external preparations such as cosmetics and quasi drugs.

However, the benzophenone derivative is U
UV-A cannot be sufficiently protected due to its low VA absorption ability, and benzotriazole derivatives have not been used in the cosmetics field from the viewpoint of safety. Further, the dibenzoylmethane derivative has a problem that it forms a chelate with a metal and is colored.

Furthermore, most of the existing UV-A absorbers are oil-soluble, and it is difficult to mix them with water-based products such as lotion, and the amount used is very small, and the UV-A absorber is very small. There was a drawback that the function of the agent was not fully exerted.

Therefore, like the oil-soluble UV-A absorber that protects the skin from UV rays in the UV-A region, water-soluble UV is used.
The development of -A absorbers has also become strongly desired.

As a result of intensive studies in view of such circumstances, the present inventors have found that a hydantoin derivative having a trehalose skeleton is a compound capable of satisfying the above-mentioned properties, and completed the present invention. .

[0009]

That is, the object of the present invention is to provide a substance which absorbs ultraviolet rays in the UV-A region and a skin external preparation containing the same, particularly a water-soluble substance which absorbs ultraviolet rays in the UV-A region. To provide an ultraviolet absorber using the same and a skin external preparation containing the same.

[0010]

This object is characterized by containing a hydantoin derivative represented by the following general formula (1), an ultraviolet absorber comprising the hydantoin derivative and the hydantoin derivative. It is achieved by a skin external preparation, in particular, a water-soluble hydantoin derivative having an ultraviolet absorbing property, an ultraviolet absorbent using the same, and a skin external preparation containing the same.

[0011]

[Chemical 2]

(Wherein A is a residue obtained by removing one hydroxyl group from trehalose, X is a hydrogen atom, a methylene oxide group, a hydroxyl group, an alkyl group having 1 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, a Represents an integer of 1 to 5, and n represents an integer of 1 to 4.)

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below.

A defined in the formula of the hydantoin derivative of the present invention is a residue obtained by removing n hydroxyl groups from trehalose, and n represents an integer of 1 to 4.

Examples of X are hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-hexyl, n-octyl, 2-
Ethylhexyl, n-decyl, n-undecyl, n-tridecyl, n-tetradecyl, n-hexadecyl, 2-
Octyldecyl, eicosanyl, methoxy, ethoxy,
Isopropoxy, n-butoxy, t-butoxy, n-hexyloxy, n-octyloxy, 2-ethylhexyloxy, n-decyloxy, n-undecyloxy, n-tridecyloxy, n-tetradecyloxy, n-hexadecyloxy, 2-octyl Examples thereof include dodecyloxy and eicosanyloxy groups. a represents the number of substitutions of X and is an integer of 1 to 5.

The hydantoin derivative of the present invention can be produced, for example, by the following method.

[0017]

[Chemical 3]

That is, a hydantoin derivative [the above general formula (2), R is an alkyl group] and trehalose [the above general formula (3)] obtained according to the method described in Japanese Patent Publication No. 7-98808 are treated with sodium hydroxide, Potassium hydroxide,
In the presence of a base such as sodium carbonate or potassium carbonate, N, N
-Reaction (transesterification reaction) is performed in a solvent such as dimethylformamide (DMF) and dimethylsulfoxide (DMSO) at room temperature to 200 ° C for 30 minutes to 50 hours. After cooling, acetone was added to the reaction solution to remove the precipitated unreacted trehalose, the organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography, recrystallization, etc. The hydantoin derivative of the present invention can be obtained.

The hydantoin derivative thus obtained is crystalline and is water-soluble when n is 1 and oil-soluble when n is 2-4.

As the hydantoin derivative obtained as described above, when n is 1, the main component is a compound in which the hydroxyl group at the 6-position of trehalose is esterified, and then the ester at the 2-position is many. can get. In addition, although the amount thereof is small, a product in which the positions other than these are esterified is also obtained. When n is 2, most of those obtained by esterifying the 6 and 6'positions are obtained, and various other components (eg 6,2'-diester, 6,3'-diester, 2,2 ') are obtained. -Diesters) are also obtained. Also, when n is 3 or 4, many various isomers are similarly obtained.

The ultraviolet absorbent according to the present invention contains at least one hydantoin derivative represented by the general formula (1), and the external skin preparation according to the present invention has the general formula (1).
It is characterized by containing at least one hydantoin derivative represented by.

The external preparation for skin of the present invention contains other ingredients usually used for external preparations for skin such as cosmetics and quasi drugs.
For example, oil, lubricating oil, ultraviolet absorbers other than the present invention, antioxidants, surfactants, preservatives, sequestering agents, perfumes,
Water, alcohol, a thickener and the like can be appropriately blended as necessary. The external preparation for skin of the present invention is not particularly limited in its field of application, and may be used in cosmetics, quasi drugs, etc. depending on the characteristics and purpose of the hydantoin derivative used in the present invention.

Here, the dosage form of the external preparation for skin of the present invention is arbitrary, and may be any dosage form such as powder, cream, paste, stick, liquid, emulsion or jelly. Further, it may be emulsified into W / O type and O / W type using an emulsifier. Although the blending amount varies depending on the above-mentioned dosage form, as a result of studying the range to achieve the object of the present invention, 0.1 to 30% by weight is preferable, and 0.2 to 20% by weight is more preferable. .

[0024]

EXAMPLES Next, the present invention will be described in detail with reference to examples. The present invention is not limited to these.

Example 1 α, α-trehalose (10 g) was added to 200 ml of N, N-.
It was dissolved in dimethylformamide (DMF). 4- (3,4-dimethoxybenzylidene) -2,5-
After adding methyl dioxo-1-imidazolidinepropionate (5.0 g) and potassium carbonate (200 mg),
The mixture was stirred at 100 ° C for 10 hours. After cooling the reaction solution, it was concentrated under reduced pressure until the liquid volume became about 50 ml. Acetone was added to this solution to precipitate unreacted trehalose, which was removed by filtration. The trehalose collected by filtration was washed with acetone, the washings were combined with the filtrate, and the solution was concentrated under reduced pressure to obtain a pale yellow viscous substance. By purifying this viscous substance by silica gel column chromatography (chloroform: methanol = 4: 1), T
Rf value of 0.1 to 0.15 in LC (silica gel) analysis (developing solvent chloroform: methanol = 6: 1)
Each component corresponding to (Component A) and 0.37 (Component B) was obtained as pale yellow crystals. The yield is 1.
5 g, and component B was 0.3 g.

The structures of the components A and B were confirmed by ¹³ C-NMR spectrum and infrared absorption spectrum. ¹³ C-NM
R spectrum is JNM LA400 F manufactured by JEOL Ltd.
It was measured using T-NMR using deuterated methanol as a solvent (internal standard: tetramethylsilane). The infrared absorption spectrum was measured by a potassium bromide tablet method using a Shimadzu FTIR-8100 Fourier transform infrared spectrophotometer.

As a result, the structures of the component A and the component B are n = 1 and n of the hydantoin derivative represented by Chemical formula 4, respectively.
It was confirmed to correspond to = 2. When n = 1,
^{From the 13} C-NMR spectrum, trehalose was esterified at the 6-position as the main component, followed by esterification at the 2-position in many cases. When n = 2, 6, 6 '
The main component was esterified.

[0028]

[Chemical 4]

Component A [compound represented by Chemical formula 4 (n = 1)] and component B [compound represented by Chemical formula 4 (n = 1)]
The ¹³ C-NMR spectrum of is shown in FIGS. 1 and 2, and the infrared absorption spectrum is shown in FIGS.

Example 2 4- (3,4-dimethoxybenzylidene) -of Example 1
Methyl 2,5-dioxo-1-imidazolidinepropionate was converted into 4- (4-methoxybenzylidene) -2,5-
The reaction was carried out in the same manner as in Example 1 except that ethyl dioxo-1-imidazolidinepropionate was used to obtain the hydantoin derivative (n = 1 to 4) represented by Chemical formula 5. The structure was confirmed by ¹³ C-NMR spectrum and infrared absorption spectrum.

[0031]

[Chemical 5]

Example 3 4- (3,4-dimethoxybenzylidene) -of Example 1
Example 1 except that the methyl 2,5-dioxo-1-imidazolidinepropionate was changed to methyl 4- (4-butoxy-3-methoxybenzylidene) -2,5-dioxo-1-imidazolidinepropionate. Perform the reaction according to
The hydantoin derivative represented by Chemical formula 6 (n = 1 to 4) was obtained. The structure was confirmed by ¹³ C-NMR spectrum and infrared absorption spectrum.

[0033]

[Chemical 6]

With respect to the compounds obtained in Examples 1 to 3, UV absorption spectra were measured with an ethanol solvent using a UV-2200 type spectrophotometer manufactured by Shimadzu Corporation, and all showed maximum absorption in the UV-A region. From this, it can be said that the hydantoin derivative of the present invention is an excellent UV-A absorber. As a typical example, FIG. 5 shows an ultraviolet absorption spectrum of the compound represented by Chemical formula 4 (n = 1) obtained in Example 1.

Examples and comparative examples of compositions containing the hydantoin derivative according to the present invention are shown below.

Example 4 (cream) A cream was prepared by a conventional method according to the formulation shown in Table 1.

[0037]

[Table 1]

Example 5 (cream) Creams were prepared by a conventional method according to the formulation shown in Table 2.

[0039]

[Table 2]

Example 6 (Lotion) A lotion having a formulation shown in Table 3 was prepared by a conventional method.

[0041]

[Table 3]

Comparative Example 1 (Cream) In the formulation of Example 4, a hydantoin derivative [Chemical Formula 4 (n =
A compound was obtained in the same formulation as in Example 4, except that the compound represented by 1) was excluded.

Comparative Example 2 (Cream) In the formulation of Example 5, a hydantoin derivative [Chemical Formula 5 (n =
A compound was obtained in the same formulation as in Example 5, except that the compound represented by 1) was excluded.

Comparative Example 3 (Lotion) In the formulation of Example 6, a hydantoin derivative [Chemical Formula 6 (n = 1
And a compound represented by 2)], except that the product was obtained in the same formulation as in Example 6.

With respect to Examples 4 to 6 and Comparative Examples 1 to 3 obtained as described above, the ultraviolet ray preventing effect was measured. As the measuring method, the above-mentioned cosmetic containing the product of the present invention was applied to the back of a human in an amount of ² mg / cm ² , and after 15 minutes, UV-A irradiation was performed. UV-A irradiation is 365n with BLB lamp
Ultraviolet rays having an energy amount of m and 9 J / cm ² were irradiated, and the minimum blackening amount (MMD) was obtained using the following formula.

[0046]

[Equation 1]

Table 4 shows the measurement results of the minimum blackening amount.

[0048]

[Table 4]

As can be seen from Table 4, the MMD value of each of the examples is higher than that of the comparative example. That is,
It can be seen that by incorporating the hydantoin derivative of the present invention, an excellent effect of preventing ultraviolet rays can be obtained.

[0050]

INDUSTRIAL APPLICABILITY The hydantoin derivative of the present invention is UV-
It is an excellent ultraviolet absorber having maximum absorption in the A region.

[Brief description of drawings]

FIG. 1 is a diagram showing a ¹³ C-NMR spectrum of hydantoin derivatization 4 (n = 1) obtained in Example 1 of the present invention.

FIG. 2 is a diagram showing a ¹³ C-NMR spectrum of hydantoin derivatization 4 (n = 2) obtained in Example 1 of the present invention.

FIG. 3 is a diagram showing an infrared absorption spectrum of hydantoin derivatization 4 (n = 1) obtained in Example 1 of the present invention.

FIG. 4 is a diagram showing an infrared absorption spectrum of hydantoin derivatization 4 (n = 2) obtained in Example 1 of the present invention.

FIG. 5 is a diagram showing an ultraviolet absorption spectrum of hydantoin derivatization 4 (n = 1) obtained in Example 1 of the present invention.

─────────────────────────────────────────────────── ─── Continuation of the front page (58) Fields surveyed (Int.Cl. ⁷ , DB name) C07H 13/04 A61K 7/00 A61K 7/42 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] 1. A compound represented by the general formula (1): (In the formula, A is a residue obtained by removing n hydroxyl groups from trehalose, X is a hydrogen atom, a methylene oxide group, and having 1 to 2 carbon atoms.
An alkyl group of 0, an alkoxy group having 1 to 20 carbon atoms, a represents an integer of 1 to 5, and n represents an integer of 1 to 4. ) The hydantoin derivative characterized by being represented by these. 2. An ultraviolet absorber comprising the hydantoin derivative according to claim 1. 3. A skin external preparation containing the hydantoin derivative according to claim 1.