JPH0543505A - Styryl ketone deribvative and skin drug for external use containing the same derivative - Google Patents

Abstract

PURPOSE:To obtain a skin drug for external use, excellent in UV-A absorbing power, capable of mixing with a non-polar base material and showing excellent properties in use by blending a styryl ketone derivative. CONSTITUTION:A compound of the formula (R<1> is isopropyl, ter-butyl or isobutyl; R<2> and R<3> are 1-18C straight or branched chain, saturated or unsaturated alkyl), e.g. (3-methoxy-4-isooctyloxystyryl t-butyl ketone is blended in an amount of 0.1-20wt.%, preferably 0.5-10wt.%. If a non-polar oil, e.g. fluid paraffin, squalane or silicone oil is used as the base oil, excellent feelings in use such as excellent spreadability, refreshing feeling and unstickiness and functions such as excellent waterproofness and resistance to flow away due to perspiration or water can be obtained.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The external preparation for skin of the present invention, especially UV-
The present invention relates to improvement of a skin external preparation having an ultraviolet ray absorbing ability in the A region.

[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. The ultraviolet rays that reach the surface of the earth have various effects on human skin. Among the ultraviolet rays reaching 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. Various UV absorbers have been developed in order to protect the skin from such harmful effects of UV-A.

As existing UV-A region ultraviolet absorbers,
Benzophenone derivatives, dibenzoylmethane derivatives, benzotriazole derivatives and the like have been used as UV-A absorbers and have been blended in skin external preparations. On the other hand, non-polar oils such as liquid paraffin, squalane, silicone oil, etc., which have excellent water resistance and do not easily wash off by sweat or a water bath, are required for external preparations for skin to which ultraviolet absorbers have been added in recent years, in order to maintain their effects. Bases have become widely used. Adopting these bases, not to mention the waterproof function,
It is also largely due to the ease of use, freshness, and non-greasy usability.

[0004]

However, the existing UV absorbers in the UV-A region have a problem that their compatibility with a non-polar oil base is extremely low. In addition, since the absorbent is generally colored crystals, there are drawbacks such as crystallization at low temperature in products and coloring of clothes, so the amount used is extremely small, and the function of the UV-A absorbent is limited. There was a drawback that it was not fully exhibited. The present invention has been made in view of the above-mentioned problems of the prior art, and an object thereof is to dissolve a non-polar oil base and to protect the skin from ultraviolet rays in the UV-A region and a skin external preparation containing the same. To provide.

[0005]

Means for Solving the Problems As a result of intensive studies by the present inventors in order to achieve the above object, they found that a styryl ketone derivative has excellent UV-A absorption and usability, and completed the present invention. Came to do. That is, the styryl ketone derivative according to claim 1 of the present application is represented by the following general formula 2.

[Chemical 2] (However, R ′ represents an isopropyl group, a tert-butyl group or an isobutyl group, and R ² and R ³ represent a linear or branched, saturated or unsaturated alkyl group having 1 to 18 carbon atoms.)

The external preparation for skin according to claim 2 is characterized in that it contains one or more styryl ketone 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 ¹ is an isopropyl group, a tert-butyl group, or an isobutyl group, and any of them can be used.

R ² and R ³ are, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group,
sec-butyl group, tert-butyl group, pentyl group, neopentyl group, hexyl group, 2-ethylbutyl group, 2-ethylhexyl group, isostearyl group, allyl group, butenyl group, oleyl group, methylenedioxy group and the like. However, branched or unsaturated alkyl groups are preferred.

The styryl ketone derivative of the present invention undergoes a condensation reaction between disubstituted benzaldehyde and methyl t-butyl ketone or methyl isopropyl ketone or methyl isobutyl ketone in a solvent using an alkali catalyst or an acidic catalyst between 0 ° C. and the boiling point of the solvent. It can be obtained by doing. Examples of the solvent used in the reaction include benzene, toluene, diethyl ether, tetrahydrofuran, dioxane, hexane, methyl alcohol, ethyl alcohol,
Any of dimethylformamide, dimethylsulfoxide, pyridine, piperidine, water and the like which are stable to alkali or acid can be used, and a mixed solvent thereof may be used. Examples of the catalyst used in the reaction include organic bases such as pyridine, piperidine, pyrrolidine, and triethylamine, inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium hydride, sodium amide, hydrochloric acid, and sulfuric acid. p-Toluenesulfonic acid or the like can also be used.

The styryl ketone derivative according to the present invention is
Room temperature liquid or low melting point solid, both 330-
It has a maximum absorption at 340 nm and can be used as a UV-A absorber. The base of the skin external preparation according to the present invention is
Any one can be used as long as the styryl ketone derivative can be dissolved therein. Especially, when a nonpolar oil such as liquid paraffin, squalane, silicone oil or the like is used as a base, the spreadability, refreshing feeling, non-greasy feeling and the like can be improved. It is possible to obtain excellent functions such as high water resistance and difficulty in flowing into sweat or water.

When a silicone-based base is used in the external preparation for skin according to the present invention, the silicone-based base is not particularly limited. For example, a chain polysiloxane such as dimethylpolysiloxane, methylpolysiloxane and methylhydrogenpolysiloxane. , Cyclic polysiloxanes such as decamethylpolysiloxane, dodecamethylpolysiloxane, and tetramethylhydrogenpolysiloxane, polyethers, fatty acid-modified polysiloxanes, higher alcohol-modified polysiloxanes, amino-modified polysiloxanes, and the like. In addition, the external preparation for skin of the present invention includes other components usually used in cosmetics, such as oil, lubricating oil, antioxidant, surfactant, preservative, sequestering agent, perfume, water, alcohol, and increasing agent. A sticky agent or the like can be appropriately blended as necessary.

The dosage form of the external preparation for skin of the present invention is arbitrary and may be any of powder, cream, paste, stick, liquid, spray, foundation and the like, and may be emulsified with an emulsifier. Good. The styryl ketone derivative of the present invention exerts a sufficient effect even when used alone, but if necessary, other UV-B absorber, for example, p-aminobenzoic acid such as Escarol 507 (manufactured by Bandaik). Derivatives, p-methoxycinnamic acid derivatives such as neoheliopan (manufactured by Herman Andreimer), salicylic acid derivatives, urocanic acid or its derivatives, 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 amount of the styryl ketone derivative used in the present invention is generally 0.1 to 20% by weight, preferably 0.1 to 20% by weight, although it varies depending on the above-mentioned dosage form and the degree of UV protection required. 0.5-10% by weight
Is.

[0014]

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.

Properties of Styryl Ketone Derivatives The following compounds 1 to 5 are examples of styryl ketone derivatives used in the present invention, and 2-hydroxy-4 is a comparative compound.
The solubility of methoxybenzophenone was tested with silicone oil, Silicone KF56 (10cs manufactured by Shin-Etsu Chemical Co., Ltd.) and squalane. Compound 1: (3-Methoxy-4-isooctyloxystyryl) -t-butylketone Compound 2: (3-Methoxy-4-isobutoxystyryl) -t-butylketone Compound 3: (3-Methoxy-4-allylxystyryl) ) -t-Butylketone compound 4: (3-isooctyloxy-4-methoxystyryl) -isopropylketone compound 5: (2-isooctyloxy-3-methoxystyryl) -isopropylketone Solubility (w of each compound at room temperature (25 ° C) / w) is shown in Table 1. The ones that are completely transparent at 25 ° C. are marked with a circle.

[Table 1] ──────────────────────────────────── Properties Solubility Silicon KF56 (50%) Squalane (30%) ──────────────────────────────────── Compound 1 Fine yellow liquid ○ ○ Compound 2 Fine Yellow viscous liquid ○ Slightly cloudy Compound 3 slightly yellow liquid ○ ○ Compound 4 slightly yellow liquid ○ ○ Compound 5 slightly yellow liquid ○ ○ ────────────────────── ────────────── Comparative compound Yellow crystals Crystal precipitation Crystal precipitation ──────────────────────────── ──────── From the above results, it is understood that all the compounds according to the present invention have excellent non-polar oil solubility.

Example 1 (3-Methoxy-4-isobutoxystyryl) -t-butyr
Preparation of Luketone 3-Methoxy-4-isobutoxybenzaldehyde 6.
20 g of ethyl alcohol containing 9 g (0.033 mol) and 3.3 g (0.033 mol) of methyl-t-butyl ketone.
A solution of 1.7 g of sodium hydroxide in 10 ml of ion-exchanged water was added dropwise at room temperature while stirring.
After completion of dropping, the bath temperature was kept at 50 to 60 ° C. and stirring was continued for 4 hours, 200 ml of ion-exchanged water was added, and the mixture was extracted with ethyl ether. After evaporating the solvent under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluted with a 10 v / v% ethyl acetate-hexane mixed solution) to obtain 6.9 g of a slightly yellow viscous liquid. The yield was about 71.7%. λ _max : 336 nm (ε = 19700) Mass spectrum M ⁺ m / e 290

Example 2 (3-Isooctyloxy-4-methoxystyryl) -isopropyl
Production of ropyl ketone 3-isooctyloxy-4-methoxybenzaldehyde 2.6 g (0.01 mol), methyl isopropyl ketone 0.86 g (0.01 mol), sodium hydroxide 0.6
g and 5 ml of ion-exchanged water, the reaction was carried out in the same manner as in Example 1, and the silica gel column chromatography (6 v /
The product was separated and purified with a v% ethyl acetate-hexane mixed solution) to obtain 2.3 g of a slightly yellow liquid. The yield was about 71.9%. λ _max : 333 nm (ε = 19500) Mass spectrum M ⁺ m / e 332 Hereinafter, specific formulation examples of the external preparation for skin according to the present invention will be described.

Example 3 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) Escalol 507 3.0 (6) (3-Methoxy-4-isobutoxystyryl) -t-butylketone 2.0 <Production method> (1 )-(6) are mixed, dissolved sufficiently and then filtered to obtain a product. <Sunscreen effect> The sunscreen cosmetic according to Example 3 and (3-methoxy-4-isobutoxystyryl) -t-butyl ketone (component
The sunscreen effect was tested using a comparative example (Escalol 507 content of 5.0%) in which (6)) was entirely replaced with Escalol 507. That is, in an actual use test on the beach, two samples were applied to each half of the body of 10 panelists and divided, and a questionnaire survey on the degree of sunburn and skin troubles were conducted. The results are shown in Table 2.

[Table 2] ------------------------------------------------ Sample application part of the comparative example of Example 3 Sample application part ------------------------------------------ Panel A ○○ B ○○ C ○ × D ○ △ E ○ × F ○ △ G △ △ H △ × I △ △ J ○ △ −−−−−−−−−−−−−−−−−−−−−−−−−−−−− −−−−−− Number of skin troubles None 3 Irritations 2 itching 2 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 styrylketone derivative was observed. The external preparation is Come of ultraviolet absorber (Esca roll 507)
The UV-protective effect was higher than that of the skin external preparation containing the compound, and the safety was high with no skin trouble.

Example 4 Sunscreen cosmetics (W / O cream
Beam) (1) 10.5% octamethylcyclotetrasiloxane (2) Dimethyl polysiloxane (100 cs) 5.0 (3) dimethylpolysiloxane (2,500,000cs) 3.0 (4) Liquid paraffin 15.0 (5) Polyether-modified silicone 6.0 (6) Escalol 507 5.0 (7) (3-Methoxy-4-isobutoxystyryl) -t-butyl ketone 4.0 (8) Purified water 43.1 (9) L- Sodium glutamate 3.0 (10) 1,3-butylene glycol 5.0 (11) Preservative 0.2 (12) Perfume 0.2 <Production method> (1) to (7), (12) are mixed, Heat and melt to 70 ℃
Keep it in the oil phase. Separately, heat and dissolve (8) to (11) to 7
Keep it at 0 ° C and use it as the water phase part. 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 5 Sunscreen cosmetics (O / W cream
Beam) (1) Decamethylcyclopentasiloxane 3.0% (2) Liquid paraffin 8.0 (3) Isopropyl myristate 2.0 (4) Vaseline 4.0 (5) cetanol 4.0 (6) Stearic acid 3.0 (7) Glyceryl monoisostearate 3.0 (8) Neoheliopan AV 3.0 (9) (3-isooctyloxy-4-methoxystyryl-t-butyl ketone 1.0 (10) Preservative 0.2 ( 11) Fragrance 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 part, and (12) to (16) are heated to 70 ° C. and completely dissolved to form an aqueous phase part. And emulsify with an emulsifying machine.
The emulsion is cooled to 30 ° C. in a heat exchanger and then filled to obtain a product.

Example 6 Sunblock Lotion (1) Dimethylpolysiloxane (5cs) 10.0% (2) Methylphenylpolysiloxane (20cs) 7.0 (3) Stearic acid 1.0 (4) Escalol 5075 0.0 (5) (3-Methoxy-4-isooctyloxystyryl) -t-butyl ketone 10.0 (6) Preservative 0.2 (7) Perfume 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. to form an oil phase portion. (8) to (11) are heated and dissolved at 70 ° C. to form an aqueous phase portion. The oil phase part is added to the water phase part and emulsified by an emulsifying machine. After cooling the emulsion to 30 ° C. in a heat exchanger, it is filled in a container,
Get sunblock lotion.

Example 7 Sunblock 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) (2-Isooctyloxy-3-methoxystyryl-isopropylol Ketone 0.5 (10) Sorbitan trioleate 1.0 (11) Preservative 0.5 (12) Vitamin E 0.05 (13) Perfume 0.5 <Production method> (1) to (5) with a Henschel mixer After mixing, a mixture of (6) to (13) heated and dissolved and mixed was added and mixed, and then crushed, and this was molded into a medium dish to obtain a sunscreen foundation.

Example 8 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) Escalol 507 5.0 (14) (3-Methoxy-4-isobutoxystyryl) -t- Butyl ketone 3.0 (15) Perfume 0.5 (16) Antioxidant 0.1 (17) Sorbitan sesquioleate 1.0 <Production method> (1) to (6) are mixed with a Henschel mixer, and (7)
~ (9), (13), (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 9 Sunscreen Makeup Base (1) Squalane 19.0% (2) Glyceryl Triisostearate 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) Pulsol MCX (manufactured by GIVAUDAN) 1. 0 (10) (3-isooctyloxy-4-methoxystyryl) -isopropylketone 1.0 (11) Preservative proper amount (12) Antioxidant proper amount (13) Perfume proper amount <Production method> (1) to (5) ), (9), (10), (12), and (13) were dissolved by stirring at 70 ° C., and then dissolved by heating at 70 ° C. in advance.
(6) to (8) and (11) were added, emulsified and dispersed, and then cooled to obtain a desired sunscreen makeup base.

As explained above, the external preparation for skin according to the present invention absorbs ultraviolet rays in the UV-A region and has excellent water resistance, and the base and other components can be freely selected. Further, it has an advantage that it is excellent in stability as a sunscreen cosmetic even when it is left under severe conditions such as under hot weather. Further, it has the advantages that it spreads well, has a refreshing feeling and is not sticky, and has extremely excellent usability, and that it is hard to flow into sweat or water and the effect of UV-A absorption is long-lasting.

[0026]

As described above, the styryl ketone derivative according to the present invention has excellent UV-A absorption ability and nonpolar oil compatibility. Further, the external preparation for skin containing it can be compounded with a non-polar base material and can exhibit excellent usability.

[Brief description of drawings]

FIG. 1 shows an example of the present invention (3-methoxy-4)
FIG. 3 is an ultraviolet absorption spectrum diagram of -isobutoxystyryl) -t-butyl ketone.

FIG. 2 shows (3-methoxy-4) according to one embodiment of the present invention.
FIG. 3 is an ultraviolet absorption spectrum diagram of -isobutoxystyryl) -t-butyl ketone.

Claims (2)

[Claims] 1. A styryl ketone derivative represented by the following general formula 1. [Chemical 1] (However, R ′ represents an isopropyl group, a tert-butyl group or an isobutyl group, and R ² and R ³ represent a linear or branched, saturated or unsaturated alkyl group having 1 to 18 carbon atoms.) 2. A skin external preparation containing one or more styryl ketone derivatives according to claim 1.