JPH05186429A - Benzylidenehydantoin derivative and skin external preparation blended with the same - Google Patents

Abstract

PURPOSE:To obtain a new benzylidenehydantoin derivative useful as a skin external preparation having ultraviolet light absorbent compound in UV-A region. CONSTITUTION:A benzylidenehydantoin derivative of formula I (R is 16-18C branched chain alkyl) such as 5-(3,4-dimethoxybenzylidene)-3-isostearylhydantoin. The compound of formula I, especially the example compound, is obtained by reacting 3,4-dimethoxybenzaldehyde with hydantoin to give 3,4- dimethoxybenzylidenehydantoin and then reacting the resultant substance with methyl branched isostearyl chloride. The bezylidenehydantoin derivative has excellent UV-A absorbency and is not colored by reaction with a metal ion. A skin external preparation blended with the benzylidenehydantoin derivative shows excellent utility.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a benzylidene hydantoin derivative and a skin external preparation containing the same, particularly UV-A.
The present invention relates to a substance having an ultraviolet absorbing ability in a region and a skin external preparation.

[0002]

2. Description of the Related Art Ultraviolet rays contained in sunlight are dermatologically long wavelength ultraviolet rays (UV-) of 400 nm to 320 nm.
A), 320 nm to 290 nm medium wavelength ultraviolet rays (UV-
B) Classified as short wavelength ultraviolet rays (UV-C) of 290 nm or less. Of these, ultraviolet rays having a wavelength of 290 nm or less are absorbed by the ozone layer and do not reach the surface of the earth.

Ultraviolet rays reaching the surface of the earth have various effects on human skin. Of the ultraviolet rays that reach the ground, UV-
B forms erythema and blisters on the skin and also promotes melanin formation. On the other hand, UV-A induces browning of the skin, lowers the elasticity of the skin and promotes the generation of wrinkles, resulting in rapid aging. It may also accelerate the onset of the erythema reaction, or enhance this reaction for some patients, and even cause phototoxicity or even a photoallergic reaction. U like this
Various UV absorbers have been developed to protect the skin from the harmful effects of VA.

As existing UV-A range ultraviolet absorbers,
Benzophenone derivatives, dibenzoylmethane derivatives, benzotriazole derivatives and the like have been used and have been blended in external preparations for skin and the like.

[0005]

However, the existing UV absorbers in the UV-A range have a problem that they react with metal ions and are colored. In addition, since the absorbent is generally colored crystals and has a defect such as coloring of clothes, the amount of the absorbent is limited to an extremely small amount, and the UV-A absorbent does not sufficiently exhibit its function. It was The present invention has been made in view of the above problems of the prior art, and an object thereof is to provide a substance that is not colored by metal ions and that protects the skin from ultraviolet rays in the UV-A region, and a skin external preparation containing the substance. Especially.

[0006]

Means for Solving the Problems As a result of intensive investigations by the present inventors in order to achieve the above object, it was found that the novel benzylidene hydantoin derivative has excellent UV-A absorption and usability, and the present invention It came to completion. That is, the benzylidene hydantoin derivative according to claim 1 of the present application is represented by the following general formula 2.

[Chemical 2] (However, R represents a branched alkyl group having 16 to 18 carbon atoms.) The external preparation for skin according to claim 2 is characterized in that it contains one or two or more benzylidene hydantoin derivatives of the chemical formula 2.

The structure of the present invention will be described in more detail below. In the above Chemical Formula 2, R may be any of a 2-hexyldecyl group, a 2-heptylundecyl group, a methyl-branched isostearyl group, and the like. The benzylidene hydantoin derivatives according to the present invention are all 320 to 370.
It has a strong absorption in nm and can be used as a UV-A absorber.

R in the general formula 2 is 8 carbon atoms.
A benzylidene hydantoin derivative having a straight chain alkyl group of -20 is disclosed in JP-A-2-111760. However, all of these compounds have low solubility in an oily base, and it is difficult to sufficiently exert the effect as an ultraviolet absorber. On the other hand, the benzylidene hydantoin derivative of the present invention has a significantly improved solubility in an oily base due to the introduction of a branched alkyl group, and as a result, exhibits a sufficient effect as an ultraviolet absorber.
The base of the external preparation for skin according to the present invention may be any as long as it can dissolve the benzylidene hydantoin derivative.

In the external preparation for skin of the present invention, other components usually used in cosmetics, such as oil, lubricating oil, antioxidant, surfactant, preservative, sequestering agent, fragrance, water, alcohol, A thickener and the like can be appropriately blended as necessary. The external preparation for skin of the present invention may have any dosage form, such as powder, cream, paste, stick, liquid, spray and foundation, and may be emulsified with an emulsifier.

The benzylidene hydantoin derivative of the present invention is sufficiently effective when used alone, but if necessary, other UV-B absorbers such as p-dimethylaminobenzoate such as 2-ethylhexyl p-dimethylaminobenzoate can be used. -Aminobenzoic acid derivative, p-methoxycinnamic acid derivative such as p-methoxykecinic acid 2-ethylhexyl ester, salicylic acid derivative, urocanic acid or its derivative, or inorganic pigments such as titanium dioxide and zinc oxide, and UV- It is also possible to use it together with the A absorbent. The blending amount of the benzylidene hydantoin derivative in the present invention is generally 0.1 to 20% by weight, preferably 0.5 although it varies depending on the above-mentioned dosage form and the degree of UV protection. 10 to 10% by weight.

[0011]

EXAMPLES The present invention will be described in more detail with reference to examples. The present invention is not limited to these examples. Further, the compounding amount is shown by weight% unless otherwise specified.

[0012]Example 1 5- (3,4-dimethoxybenene
Dilidene) -3-isostearylhydantoin 83 g of 3,4-dimethoxybenzaldehyde, hydanto
In 50 g, 2-aminoethanol 1.1 g, sodium hydroxide
Thorium 1.0 g, ion-exchanged water 250 ml mixture 9
After heating and stirring at 0 ° C for 5 hours, the precipitated solid was taken
It was Rinse well with water, wash with methanol and dry.
4-dimethoxybenzylidene hydantoin was obtained (yellow
Solid, mp; 274.5 ° C). The obtained 3,4-dimeth
Xybenzylidene hydantoin 4.4 g, methyl branch a
Sostearyl chloride 5.8g, anhydrous potassium carbonate
1 mixture of 2.8 g and 70 ml of dimethylformamide
After heating and stirring at 10 ° to 120 ° C for 5 hours, insoluble matter is removed.
I made a kiss. Dimethylformamide was distilled off under reduced pressure, and the residue was
Silica gel column chromatography (25% ethyl acetate
Eluate with a mixed solution of ru-hexane) to obtain a colorless solid.
8 g was obtained. The mass spectrum of this compound,¹H-NM
From the R spectrum, the desired 5- (3,4-dimethoxyben
Dilidene) -3-isostearyl hydantoin
And confirmed. Property mp: 64-65 ° C Mass spectrum M⁺500, λ_max(Ethanol) 344
nm (ε = 26500) ¹ 1 H-NMR (400M) (CDCl₃) Characteristic signal
Only shown. δ3.60t, 2H, δ3.92s, 3H, δ3.94
s, 3H, δ6.69s, 1H, δ6.91d, 1H
(J = 8.30), δ6.94s, 1H, δ7.06
d, 1H (J = 8.30), δ8.50bs, 1H

Example 2 5- (3,4-dimethoxybenene
Dilydene) -3- (2-hexyldecyl) hydantoin 3,4-dimethoxybenzylidene hydantoin 4.4
A mixture of g, 5.7 g of 2-hexyldecyl chloride, 2.8 g of anhydrous potassium carbonate and 90 ml of dimethylformamide was heated and stirred at 125 to 135 ° C for 5 hours and then cooled to room temperature. The insoluble material was separated by distillation, dimethylformamide was distilled off under reduced pressure, and the residue was separated and purified by silica gel column chromatography (eluted with 25% ethyl acetate-hexane mixed solution) to obtain 2.8 g of a colorless solid.

This compound has a mass spectrum of ¹ H--N
From the MR spectrum, it was confirmed to be the target 5- (3,4-dimethoxybenzylidene) -3- (2-hexyldecyl) hydantoin. Properties mp: 96-97 ° C. λ mass spectrum M ⁺ 472, λ _max (ethanol) 34
4 mm (ε = 27400) ¹ H-NMR (400 M) (CDCl ₃ ) Only the characteristic signal is shown. δ3.50d, 2H (J = 7.33), δ3.92s,
3H, δ3.94s, 3H, δ6.69s, 1H, δ
6.91d, 1H (J = 8.30), δ6.93s, 1
H, δ7.09d, 1H (J = 7.81), δ8.59
bS, 1H

UV absorption effect Example 2 (5- (3,4-dimethoxybenzylidene) -3- (2-hexyldecyl) hydantoin) of the present invention and Example 3 (5-3,4-dimethoxybenzylidene)
-3- (2-heptylundecyl) hydantoin: 2-hexyldecyl chloride was added to 2-
It was prepared by using heptyl undecyl chloride) and Comparative Compound 1 (2-hydroxy-4-methoxybenzophenone; UV-A absorber), and the ultraviolet absorption effect was measured by absorbance according to the following measuring method. (Measurement method) 10 ppm ethanol (99.5%, reagent grade) solutions of Example Compounds 2 and 3 and Comparative Compound 1 were prepared and analyzed by JASCO (using a quartz cell (1 cm × 1 cm)). It was measured with a UVIDEC-610 type spectrophotometer manufactured by Co., Ltd.

The results are shown in Table 1.

[Table 1] ──────────────────────────────────── Wavelength (nm) Example 2 Example 3 Comparative compound 1 ──────────────────────────────────── 300 0.16 0.15 0.39 310 0.27 0.26 0.35 320 0.38 0.33 0.40 330 330 0.48 0.42 0.42 340 0.55 0.52 0.34 350 0.57 0.50 0.20 360 0.48 0.40 0.11 370 0.31 0.31 0.03 380 0.10 0.12 0.00 ─────────────────────── ─────────────── These results show that the compound of the Example is in the UV-A region and is more sensitive than the comparative compound 2-hydroxy-4-methoxybenzophenone. It has a strong UV absorption effect and a high sun protection effect.

Properties of Benzylidene Hydantoin Derivatives The above-mentioned benzylidene hydantoin derivatives 2 and 3 according to the present invention, and 2-hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methylphenylbenzotriazol trivalent iron as comparative compounds. The reaction with ions was tested. (Method) 0.1 g of each of the compounds 2 and 3 of the present invention and the comparative compound was added to 99.5% ethyl alcohol (special grade reagent).
After dissolving in 10 ml and adding 2 ml of 99.5% ethyl alcohol (special grade reagent) containing 0.02% ferric chloride (FeCl ₃ ) and stirring well, a change in color tone of the solution was observed.

The results are shown in Table 2 below.

[Table 2] ──────────────────────────────────── Before the addition of the compound FeCl _{3 After the} addition of FeCl ₃ ─ ─────────────────────────────────── Inventive Compound 2 No slight yellow change Inventive Compound 3 slight yellow change None 2-Humanoxy-4-methoxybenzophenone Colored in pale yellow brown (Comparative compound) 2-Humanoxy-4-methylphenylbenzene triazol Colored in pale yellow (Comparative compound) ─────────── ────────────────────────── From the above results, it is understood that none of the compounds according to the present invention reacts with metal ions. Hereinafter, specific formulation examples of the external preparation for skin according to the present invention will be described.

Example 4 Sunscreen Cosmetic (Oil Type) (1) Decamethylcyclopentasiloxane 47.0% (2) Dimethylpolysiloxane (10cs / 25 ° C) 20.0 (3) Methylphenylpolysiloxane (20cs) / 25 ° C) 18.0 (4) Silicone resin 10.0 (5) P-Dimethylaminobenzoic acid 2-ethylhexyl ester 3.0 (6) 5- (3,4-Dimethoxybenzylidene) -3- (2- Hexyldecyl) Hindantin 2.0 <Production Method> (1) to (6) are mixed, sufficiently dissolved and then filtered to obtain a product. <Sunscreen effect> The sunscreen cosmetic according to Example 4 and 5- (3,4-dimethoxybenzylidene) -3.
The sunscreen effect was tested using a comparative example in which the total amount of-(2-hexyldecyl) hydantoin (component (6)) was replaced with P-dimethylaminobenzoic acid 2-ethylhexyl ester.

That is, in an actual use test at the beach, two samples were applied separately to each half of the body of 10 panelists, and a sunburn condition questionnaire survey and skin trouble survey were conducted. The results are shown in Table 3.

[Table 3] ──────────────────────────────────── Sample application part of the comparative example of Example 4 Sample application part ──────────────────────────────────── Panel A ○ ○ B △ △ C ○ × D ○ × E ○ × F ○ △ G ○ △ H △ × I ○ △ J ○ △ ─────────────────────────────── ────── Number of skin troubles N / A 2 cases Itching 2 cases Rash 1 case ─────────────────────────────── ────── Evaluation criteria for degree of sunburn Strong sunburn symptoms were observed. × Sunburn symptoms were observed. △ Sunburn symptoms were hardly observed. ○ From these results, skin containing benzylidene hydantoin derivative was observed. Use agent, conventional ultraviolet absorber (P- dimethylaminobenzoic acid 2-ethylhexyl ester) high ultraviolet protection effects than external skin preparation containing a combination of, were those high safety without skin troubles.

Example 5 Sunscreen Cosmetic (W / O Cream) (1) Octamethylcyclotetrasiloxane 10.5% (2) Dimethylpolysiloxane (100cs) 5.0 (3) Dimethylpolysiloxane (2,500,000cs) 3.0 (4) Liquid paraffin 15.0 (5) Polyether-modified silicone 6.0 (6) P-Dimethylaminobenzoic acid 2-ethylhexyl ester 5.0 (7) 5- (3.4-Dimethoxybenzylidene) -3 -Isostearyl hydantoin 4.0 (8) Purified water 43.1 (9) Sodium L-glutamate 3.0 (10) 1,3-butylene glycol 5.0 (11) Preservative 0.2 (12) Perfume 0 .2 <Production Method> (1) to (7) and (12) are mixed, dissolved by heating and maintained at 70 ° C. to form an oil phase part. Separately, (8) to (11) are dissolved by heating and kept at 70 ° C to form an aqueous phase. The water phase part is added to this oil phase part, and it is sufficiently emulsified by an emulsifying machine. After emulsification, cool while stirring, and when the temperature becomes 35 ° C or lower, pour into a container and allow to cool to solidify.

Example 6 Sunscreen Cosmetic (O / W Cream) (1) Decamethylcyclopentasiloxane 3.0% (2) Liquid Paraffin 8.0 (3) Isopropyl myristate 2.0 (4) Vaseline 4 0.0 (5) Cetanol 4.0 (6) Stearic acid 3.0 (7) Glyceryl monoisostearate 3.0 (8) P-methoxycinnamic acid 2-ethylhexyl ester 3.0 (9) 5- ( 3,4-Dimethoxybenzylidene) -3- (2-hexyldecyl) hydantoin 1.0 (10) Preservative 0.2 (11) Perfume 0.2 (12) Glycerin 10.0 (13) Propylene glycol 5.0 (14) Hyaluronic acid 0.01 (15) Potassium hydroxide 0.2 (16) Purified water 53.39 <Production method> (1) to (11) are heated and stirred at 70 ° C to form an oil phase portion. (12)
(16) is heated to 70 ° C. to completely dissolve it, and then used as an aqueous phase part.
The oil phase part is added to the water phase part and emulsified by an emulsifying machine. The emulsion is cooled to 30 ° C. in a heat exchanger and then filled to obtain a product.

Example 7 Sunblock Lotion (1) Dimethylpolysiloxane (5cs) 3.0% (2) Methylphenylpolysiloxane (20cs) 17.0 (3) Stearic acid 1.0 (4) P-Dimethylamino Benzoic acid 2-ethylhexyl ester 5.0 (5) 5- (3,4-dimethoxybenzylidene) -3- (2-heptyl undecyl) hydantoin 7.0 (6) Preservative 0.2 (7) Perfume 0.0. 2 (8) Glycerin 5.0 (9) Montmorillonite 0.5 (10) Potassium hydroxide 0.2 (11) Purified water 60.9 <Production method> (1) to (7) are heated and stirred at 70 ° C. The oil phase is used. (8) ~
(11) is heated to 70 ° C. and dissolved to form an aqueous phase. The oil phase part is added to the water phase part and emulsified by an emulsifying machine. The emulsion is cooled to 30 ° C. in a heat exchanger and then filled in a container to obtain a sunscreen lotion.

Example 8 Sunscreen Foundation (1) Silicone treated titanium oxide 9.5% (2) Silicone treated mica 40.0 (3) Silicone treated talc 20.45 (4) Silicone treated iron oxide 7.5 ( 5) Spherical nylon powder 10.0 (6) Trimethylolpropane triisostearate 5.0 (7) Squalane 3.0 (8) Beeswax 2.0 (9) 5- (3,4-Dimethoxybenzidine)- 3- (2-Hexyldecyl) hydantoin 0.5 (10) Sorbitan trioleate 1.0 (11) Preservative 0.5 (12) Vitamin E 0.05 (13) Perfume 0.5 <Production method> (1) ~ (5) is mixed with a Henschel mixer, and (6) ~
(13) was heated and dissolved and mixed, and then pulverized after adding and mixing,
This was molded into an inner dish to obtain a sunscreen foundation.

Example 9 Sunscreen Stick Cosmetic (1) Titanium oxide 10.0% (2) Zinc oxide 7.0 (3) Mica 16.0 (4) Red iron oxide 1.5 (5) Yellow iron oxide 1.5 (6) Black iron oxide 1.0 (7) Dimethylpolysiloxane (20cs) 29.4 (8) Trimethylolpropane-tri-2-ethylhexanoate 8.0 (9) Liquid paraffin 7.0 (10) Microcrystalline wax 2.0 (11) Ceresin 1.0 (12) Solid paraffin 6.0 (13) P-Dimethylaminobenzoic acid 2-ethylhexyl ester 5.0 (14) 5- (3.4-dimethoxybenzylidene) ) -3-Isostearyl hydantoin 3.0 (15) Perfume 0.5 (16) Antioxidant 0.1 (17) Sorbitan sesquioleate 1.0 <Production method> Mix (1) to (6) with a Henschel mixer. , (7) to (9), (1
3), (14), (16), and (17) are added to and mixed by heating and stirring and mixing. Next, a solution obtained by dissolving (10) to (12) and (15) is added to the above mixture, mixed sufficiently, and then molded into a stick shape.

Example 10 Sunscreen Makeup Base (1) Squalane 19.0% (2) Glyceryltriisostearate 10.0 (3) Isopar G 5.0 (4) Sorbitan Sesquioleate 1.0 (5) Poly Siloxane Ethylene-modified organopolysiloxane 3.0 (6) Purified water 45.0 (7) 1,3-butylene glycol 5.0 (8) Fine particle titanium oxide 10.0 (9) P-methoxycinnamic acid 2-ethylhexyl Ester 1.0 (10) 5- (3.4-Dimethoxybenzylidene) -3- (2-hexyldecyl) hydantoin 1.0 (11) Preservative proper amount (12) Antioxidant proper amount (13) Perfume proper amount < Manufacturing method> (1) to (5), (9), (10), (12), and (13) were dissolved by stirring at 70 ° C., and heated and dissolved at 70 ° C. in advance (6) to (8),
(11) was added, emulsified and dispersed, and then cooled to obtain a desired sunscreen makeup base.

As described above, the external preparation for skin according to the present invention absorbs ultraviolet rays in the UV-A region, and coloring by metal ions is not recognized. Further, it has an advantage that it is excellent in stability even when left as a sunscreen cosmetic under severe conditions such as under hot weather.

[0028]

As described above, according to the benzylidene hydantoin derivative of the present invention, excellent UV-A can be obtained.
Along with its absorption capacity, it does not react with metal ions and become colored. Further, an external preparation for skin containing the same can exhibit excellent usability.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Keiichi Uehara 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Prefecture Shiseido Research Institute Co., Ltd.

Claims (2)

[Claims] 1. A benzylidene hydantoin derivative represented by the following general formula 1. [Chemical 1] (However, R represents a branched alkyl group having 16 to 18 carbon atoms) 2. A skin external preparation containing one or more benzylidene hydattoin derivatives according to claim 1.