JPH0710806A - Cinnamic ester derivative, ultraviolet light absorber and external preparation for skin using the same - Google Patents

Abstract

PURPOSE:To obtain a new cinnamic ester derivative useful for various external preparations for skin as an UV-A absorber showing high solubility in a non- polar oil, having excellent UV-A absorbing ability and no change in color in the presence of a metal ion. CONSTITUTION:A cinnamic ester of the formula (R<1> is a 1-8C alkyl; R<2> is a 1-18C alkyl or alkenyl; (n) is 2-3 with the proviso that 2,3,4-trialkoxy-substituted derivative and 3,4,5-trialkoxy-substituted derivative are excluded) such as 2,3,4- trimethoxysuccinic acid 2-ethylhexyl ester. The cinnamic ester of the formula, for example, is obtained by treating an alkoxycinnamic acid with an alkyl alkenyl alcohol in a hydrocarbon or an aromatic solvent by the use of an acid catalyst through dehydration.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cinnamic acid ester derivative and a skin external preparation using the same, and more particularly to a substance having an absorbability in the UV-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 320 nm to 400 nm.
A) Medium wavelength ultraviolet rays (UV-
B), and short wavelength ultraviolet rays (UV-C) of 290 nm or less
are categorized. Of these, UV-C is almost absorbed by the ozone layer before it reaches the surface of the earth, so most of the ultraviolet rays that reach the ground are UV-A and UV-B. Although UV-A and UV-B have various effects on human skin, the sunburn phenomenon is most prominent.

UV-B sunburn is generally a sunbu
It is called rn and causes inflammatory symptoms such as erythema and blistering on the skin, whereas sunburn due to UV-A is a browning of the skin generally called suntan, which reduces the elasticity of the skin and causes wrinkles. And bring about a rapid aging phenomenon. UV-A is also known to accelerate the initiation of the erythema reaction, but it may enhance the erythema reaction in some patients, which causes phototoxicity or photoallergic reaction. Sometimes.

In order to prevent such harmful effects caused by ultraviolet rays, it is effective to appropriately select and use an ultraviolet absorbent suitable for the purpose. Various ultraviolet absorbents have been developed so far, and external preparations for skin are used. Etc. have been compounded. However, the number of UV-A absorbers is much smaller than that of UV-B absorbers, and for example, only benzophenone derivatives, dibenzoylmethane derivatives, benzotriazole derivatives and the like are known.

On the other hand, in order to maintain the effect of the ultraviolet absorber in the skin external preparation, it is important to make the skin external preparation excellent in water resistance and not easily washed off by sweat or water bath. For this reason, in recent years, non-polar oils such as liquid paraffin, squalane, and silicone oil have been widely used as a base for cosmetics for preventing ultraviolet rays. These bases have not only a water-resistant function, but also have a great use feeling such as good spreadability, a refreshing feeling, and non-stickiness.

[0006]

However, existing UV-A absorbers have extremely low solubility in non-polar oil bases and are generally dark-colored crystals, resulting in low temperature crystallization in the product. Or, because it adheres to clothes and is colored, the amount of its use is limited in the external preparation for skin, particularly in the external preparation for skin based on nonpolar oil which has been widely used in recent years,
There has been a problem that the function of the UV-A absorber is not fully exhibited. In addition, it has a drawback that when metal ions are present, it reacts and discolors. The present invention has been made in view of the above problems of the prior art, and its purpose is to:
To provide a UV-A absorber which is easily dissolved in a non-polar oil base, has no problems such as crystallization in the product, and does not discolor by metal ions, and a skin external preparation containing the same. It is in.

[0007]

Means for Solving the Problems As a result of intensive studies to achieve the above object, the present inventors have found that certain cinnamic acid ester derivatives have excellent UV-A absorption ability,
Moreover, they have found that they are also very excellent in usability, and have completed the present invention. That is, the cinnamic acid ester derivative and the ultraviolet absorber according to the present invention are represented by the following general formula 2.

[0008]

[Chemical 2] (In the formula, R ¹ is a C ₁ -C ₈ alkyl group, and R ² is C ₁ -C ₁₈
Is an alkyl group or an alkenyl group, and n is an integer of 2 to 3. However, the 2,3,4-trialkoxy substitution product and the 3,4,5-trialkoxy substitution product are excluded. The external preparation for skin according to the present invention is characterized by containing one or more of the cinnamic acid ester derivatives.

The structure of the present invention will be described in detail below. In the cinnamic acid ester derivative represented by the general formula 2, R ¹ is an alkyl group having 1 to 8 carbon atoms, which may be linear or branched. Examples of the alkyl group include a methyl group, an ethyl group, a propyl group,
A linear alkyl group such as butyl group, pentyl group, hexyl group, heptyl group, octyl group, or isopropyl group, isobutyl group, t-butyl group, neopentyl group, 2
Examples thereof include branched alkyl groups such as an ethylbutyl group and a 2-ethylhexyl group. R ² has 1 to 1 carbon atoms
8 is an alkyl group or an alkenyl group such as R
^In addition to the alkyl groups exemplified as ¹ , 2-hexyldecyl group, 2-heptylundecyl group, branched alkyl groups such as methyl-branched isostearyl group, dodecyl group, tetradecyl group, hexadecyl group, octadecyl group, oleyl group A linear alkyl group or alkenyl group such as

In the general formula 2, n is 2
It is an integer of 3 and represents the number of substituents of R ¹ in the aromatic ring. (However, since the 2,3,4-trialkoxy-substituted product and the 3,4,5-trialkoxy-substituted product have weak absorption in the UV-A region, they are excluded.) Cinnamic acid according to the present invention The ester derivative can be easily produced by a general esterification reaction. For example, alkoxycinnamic acid and an alkyl or alkenyl alcohol are dehydrated in a hydrocarbon solvent or an aromatic solvent using an acid catalyst such as an organic acid or an inorganic acid, or a base catalyst such as an organic base or an inorganic base. There are a treatment method, a method of reacting an alkoxycinnamic acid halogenide and an alkyl or alkenyl alcohol in the absence of a solvent or in a nonaqueous solvent in the presence of the above base. By any of these methods, the desired cinnamic acid ester derivative can be obtained in high yield.

Each of the cinnamic acid ester derivatives of the present invention has the following features. That is, it has a strong absorptivity in the UV-A region of 320 nm or more. High solubility in non-polar oils. Does not discolor even in the presence of metal ions. Due to these characteristics, the cinnamic acid ester derivative of the present invention is extremely useful without causing problems in use such as solubility, stability and discoloration that the above-mentioned existing UV-A absorber has. It is a UV-A absorber and can be suitably applied to various skin external preparations.

The base used in the external preparation for skin of the present invention may be any one as long as it can dissolve the cinnamic acid ester derivative, but liquid paraffin, squalane,
By using a non-polar oil such as a silicone-based oil agent, it is possible to obtain excellent feeling of use such as good spreadability, refreshing feeling, and non-greasiness, and water resistance that is hard to be washed away by water or sweat. The silicone oil used as the base is not particularly limited, but for example, dimethylpolysiloxane,
Chain polysiloxanes such as methylpolysiloxane and methylhydrogenpolysiloxane, cyclic polysiloxanes such as decamethylcyclopolysiloxane, dodecamethylcyclopolysiloxane, and tetramethylhydrogencyclopolysiloxane, polyethers, fatty acid-modified polysiloxanes, Examples thereof include higher alcohol-modified polysiloxane and amino acid-modified polysiloxane.

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 an emulsifier is used. It may be an emulsion. The amount of the cinnamic acid ester derivative in the external preparation for skin of the present invention is not particularly limited and varies depending on how much ultraviolet absorption effect is required. 20% by weight, preferably 0.5-
It is 10% by weight.

The cinnamic acid ester derivative of the present invention exerts its effect sufficiently even if used alone, but it may be used in combination with other UV-A absorber or UV-B absorber, if necessary. Is also possible. In fact, in sunscreen cosmetics and the like, UV-B absorbers are often added together with UV-A absorbers. Examples of UV-B absorbers include p-aminobenzoic acid derivatives such as p-dimethylaminobenzoic acid 2-ethylhexyl ester and p-methoxycinnamic acid derivatives such as p-methoxycinnamic acid 2-ethylhexyl ester. , Salicylic acid derivatives, urocanic acid or its derivatives,
Alternatively, inorganic pigments such as titanium dioxide and zinc oxide may be used.

In addition to the above-mentioned components, the external preparation for skin of the present invention is a component usually used in medicines, cosmetics and the like, for example,
Oils, lubricating oils, antioxidants, surfactants, preservatives, sequestering agents, fragrances, water, alcohols, thickeners, agents and the like can be appropriately added within a range that does not impair the effects of the present invention.

[0016]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited thereto. In addition, in the following description, compounds 1 to 5 represent the following compounds, and unless otherwise specified, all compounding amounts are% by weight. Compound 1: 2,4,5-Trimethoxycinnamic acid 2-ethylhexyl ester Compound 2: 2,5-Dimethoxycinnamic acid 2-ethylhexyl ester Compound 3: 3,4-Dimethoxycinnamic acid isostearyl ester Compound 4: 2,4-Dimethoxycinnamic acid isopropyl ester Compound 5: 2,4,5-trimethoxycinnamic acid oleyl ester

[Production of Cinnamic Acid Ester Derivative] Production Example 1 (Production of Compound 1) A mixed solution of 5.0 g of 2,4,5-trimethoxycinnamic acid, 5 g of thionyl chloride and 30 ml of benzene was refluxed for 2 hours. ,
It was dried under reduced pressure. To this, 30 ml of toluene was added and dissolved, 2.7 g of 2-ethylhexanol and 10 ml of pyridine.
The mixed solution of was added dropwise at room temperature and reacted at 70 to 80 ° C. for 2 hours. After completion of the reaction, the reaction solution was poured into 200 ml of ice water, washed with 2N-hydrochloric acid, thoroughly washed with water, and dried. The solvent was evaporated under reduced pressure, and the residue was separated and purified by silica gel column chromatography (eluted with 20% ethyl acetate-hexane mixed solution) to obtain 5.8 g of the desired product as a pale yellow oil. still,
The maximum absorption wavelength (λmax) and mass spectrum data of the obtained target substance were as follows. λmax (ethanol) 350 nm (ε = 16,1
00) Mass spectrum M ⁺ m / e 350

Production Example 2 (Production of Compound 2) The reaction was carried out in the same manner as in Example 1 using 5.0 g of 2,5-dimethoxycinnamic acid, 5 g of thionyl chloride and 30 ml of benzene to obtain cinnamic acid chloride. It was This is dissolved in 30 ml of toluene, and a mixed solution of 3.2 g of 2-ethylhexanol and 10 ml of pyridine is added dropwise at room temperature to 60 to 70.
The reaction was carried out at 0 ° C for 2 hours. After the completion of the reaction, the same treatment as in Production Example 1 was carried out to obtain 5.4 g of a target product as a pale yellow liquid. The maximum absorption wavelength (λmax) and mass spectrum data of the obtained target substance were as follows. λmax (ethanol) 352 nm (ε = 7,30
0) Mass spectrum M ⁺ m / e 320

Production Example 3 (Production of Compound 3) 3,4-dimethoxycinnamic acid 5.0 g, isostearyl alcohol 6.5 g, and thionyl chloride 5.0 g were used in the same manner as in Production Example 1 or Production Example 2. The reaction and treatment were carried out to obtain 7.6 g of the desired product as a colorless oil. The maximum absorption wavelength (λmax) and mass spectrum data of the obtained target substance were as follows. λmax (ethanol) 324 nm (ε = 20,3
00) Mass spectrum M ⁺ m / e 460

[Solubility in Non-Polar Oil] Using the compounds 1 to 5 as the cinnamic acid ester derivative of the present invention and 2-hydroxy-4-methoxybenzophenone (comparative compound a) as a comparative example, room temperature (25 The solubility in silicone oil and squalane at (° C.) Was examined. still,
Silicone-based oil agents include silicone KF56 (10c
s, manufactured by Shin-Etsu Chemical Co., Ltd.). As a result, as shown in Table 1, all of the compounds 1 to 5 which are the cinnamic acid ester derivative of the present invention are liquid at room temperature, and the silicone KF
In comparison with 56 and squalane, 10% or more is dissolved in 2-hydroxy-4-methoxybenzophenone of Comparative Compound a, which is a solid at room temperature and has low solubility in silicone oil and squalane, and in any case, crystallized. Was deposited.

From the above, the cinnamic acid ester derivative according to the present invention has excellent solubility in non-polar oils and causes problems such as crystal precipitation which has been a problem with conventional UV absorbers. It became clear that it is not a UV absorber.

[Table 1] ──────────────────────────────────── Sample Properties Solubility * Silicon KF56 Squalane ──────────────────────────────────── Compound 1 Light yellow liquid ○ ○ Compound 2 Light yellow liquid ○ ○ Compound 3 colorless liquid ○ ○ Compound 4 colorless liquid ○ ○ Compound 5 pale yellow liquid ○ ○ ──────────────────────────────── ───── Comparative compound a Yellow crystal × × ──────────────────────────────────── ※ Each Appearance when each sample was dissolved in non-polar oil at 10 w / w%: ○: Complete dissolution, ×: No dissolution (crystal precipitation)

[Discoloration by Metal Ions] Samples 1 to 5 as the cinnamic acid ester derivative of the present invention, and Comparative compounds a and 2-hydroxy-5-methylphenylbenzotriazole (Comparative compound b) as comparative examples The discoloration caused by metal ions was investigated by the following method. That is, 0.1 g of each sample was dissolved in 10 ml of ethanol, and 2 ml of an ethanol solution containing ferric chloride (FeCl ₃ ) 0.02% was added and well stirred, and then the color tone change of the solution was observed. All the ethanol used in this test had a purity of 99.5% (special grade reagent).

As a result, as shown in Table 2, compounds 1 to
No change in color tone of the test liquid was observed in any of the cinnamic acid ester derivatives of No. 5, but in the test liquids of Comparative Compound a and Comparative Compound b, addition of Fe ^{3+ changed} the color to light yellow → brown and light yellow → blue, respectively. Discolored. As described above, the cinnamic acid ester derivative of the present invention does not react with metal ions, and is an excellent UV-A that does not discolor even in the presence of metal ions.
It was revealed to be an absorbent.

[0024]

[Table 2] ──────────────────────────────────── Color of the test solution FeCl ₃ before addition After addition of FeCl ₃ ──────────────────────────────────── Compound 1 Slight yellow No change Compound 2 Slight yellow No change Compound 3 No change No change Compound 4 No change No change Compound 5 Light yellow No change ───────────────────────────────── ──── Comparative compound a pale yellow brown Comparative compound b pale yellow blue ────────────────────────────────── ──

[UV Protection Effect Test] Formulation Example 1 (Sunscreen Oil) The UV protection effect of the cinnamic acid ester derivative of the present invention was actually examined using a human body panel as follows. <Preparation of sunscreen oil> As a sample, the compound 1
2,4,5-trimethoxycinnamic acid 2-ethylhexyl ester was sufficiently dissolved in the following formulation according to the following formulation, and then filtered to prepare a sunscreen oil (Formulation Example 1). Further, as a comparative example, a sunscreen oil containing p-dimethylaminobenzoic acid 2-ethylhexyl ester in place of Compound 1 (total blending amount with respect to cosmetics is 5.0% by weight) was similarly prepared.

Decamethylcyclopentasiloxane 47.0 wt% Dimethylpolysiloxane (10cs / 25 ° C) 20.0 Methylphenylpolysiloxane (20cs / 25 ° C) 18.0 Silicone resin 10.0 p-Dimethylaminobenzoic acid 2- Ethylhexyl ester 3.0 2,4,5-Trimethoxycinnamic acid 2-Ethylhexyl ester 2.0

<Test Method> The sunscreen oils of Formulation Example 1 and Comparative Example were applied to the left and right half of each body of 10 panelists, and the degree of sunburn on the beach was evaluated according to the following criteria. ○: Almost no sunburn was observed △: Mild sunburn was observed ×: Strong sunburn was observed <Results> When oil was applied, 70% of the panelists said that they had almost no sunburn, and the remaining 30% of the panelists had only mild sunburn symptoms, and some panelists had severe sunburn symptoms. There wasn't. On the other hand, in the oil of Comparative Example, 80% of panelists complained of severe or mild sunburn symptoms, and 50% of the panelists had severe sunburn symptoms.

Further, no skin trouble was observed in the sunscreen oil-applied part of Formulation Example 1, but problems such as skin tightness, itchiness and rash occurred in the application part of the comparative example. From the above, it has been clarified that the external preparation for skin containing the cinnamic acid ester derivative of the present invention has an excellent effect of protecting ultraviolet rays and prevents sunburn and skin troubles caused by ultraviolet rays.

[0029]

[Table 3] ─────────────────────────────── Panel Sunburn Evaluation Formulation Example 1 Comparative Example ─────── ───────────────────────── A ○ ○ B ○ × C △ × D ○ △ E △ △ F ○ × G ○ ○ H ○ △ I △ △ J ○ × ──────────────────────────────── No skin trouble 2 cases 2 cases itch 3 cases rash 1 case ────────────────────────────────

The skin external preparations of the following formulation examples 2 to 7 were prepared and tested for UV protection in the same manner as in formulation example 1. All had excellent effects and prevented sunburn and skin troubles due to UV radiation. It was something to do. Formulation Example 2 (W / O cream) A W / O cream was prepared according to the following formulation. As for the preparation method, the oil phase part and the water phase part were each melted by heating and kept at 70 ° C., the water phase part was added to the oil phase part, and the mixture was sufficiently emulsified by an emulsifying machine. After emulsification, the mixture was cooled to 35 ° C. or lower with stirring, poured into a container, allowed to cool and solidified to obtain a W / O cream. <Oil phase part> Octamethylcyclotetrasiloxane 10.5 wt% Dimethylpolysiloxane (100cs) 5.0 Dimethylpolysiloxane (2,500,000cs) 3.0 Liquid paraffin 15.0 Polyether-modified silicone 6.0 p-methoxy cinnamon Acid 2-ethylhexyl ester 5.0 2,4,5-Trimethoxycinnamic acid 2-ethylhexyl ester 4.0 Perfume 0.2 <Water phase part> Purified water 43.1 L-Glutamate sodium 3.0 1,3 -Butylene glycol 5.0 Preservative 0.2

Formulation Example 3 (O / W cream) An O / W cream was prepared according to the following formulation. The preparation method is such that the oil phase part and the water phase part are each heated and dissolved at 70 ° C.,
The oil phase part was added to the water phase part and sufficiently emulsified by an emulsifying machine. The emulsion was cooled to 30 ° C. with a heat exchanger and then filled in a container to obtain an O / W cream. <Oil phase part> Decamethylcyclopentasiloxane 3.0 wt% Liquid paraffin 8.0 Isopropyl myristate 2.0 Vaseline 4.0 Cetanol 4.0 Stearic acid 3.0 Glyceryl monoisostearate 3.0 p-Dimethylamino Benzoic acid 2-ethylhexyl ester 3.0 2,5-dimethoxypropylcinnamic acid 2-ethylhexyl ester 1.0 Preservative 0.2 Perfume 0.2 <Water phase part> Glycerin 10.0 Propylene glycol 5.0 Hyaluronic acid 0.01 potassium hydroxide 0.2 purified water 53.39

Formulation Example 4 (Lotion) A lotion was prepared according to the following formulation in the same manner as in Formulation Example 3 above. <Oil phase part> Dimethylpolysiloxane (5cs) 10.0wt% Methylphenylpolysiloxane (20cs) 7.0 Stearic acid 1.0 p-Methoxycinnamic acid 2-ethylhexyl ester 5.0 3,4-Dimethoxycinnamate Isostearyl acid 10.0 Preservative 0.2 Perfume 0.2 <Water phase part> Glycerin 5.0 Montmorillonite 0.5 Potassium hydroxide 0.2 Purified water 60.9

Formulation Example 5 (dual use foundation) A dual use foundation was prepared according to the following formulation. The preparation method is to mix Part A with a Henschel mixer,
What was heated and melt | dissolved in this part B was added and mixed, it grind | pulverized, and this was shape | molded to the inside plate, and the dual-use foundation was obtained. <Part A> Silicone treated titanium oxide 9.5 wt% Silicone treated mica 40.0 Silicone treated talc 20.45 Silicone treated iron oxide 7.5 Spherical nylon powder 10.0 <Part B> Trimethylolpropane triisostearate 5. 0 Squalane 3.0 Bee wax 2.0 2,4-Dimethoxycinnamic acid isopropyl ester 0.5 Sorbitan trioleate 1.0 Vitamin E 0.05 Preservative 0.5 Perfume 0.5

Formulation 6 (stick cosmetic) A sunscreen stick cosmetic was prepared according to the following formulation. The preparation method is as follows: Part A is mixed with a Henschel mixer, to which part B is heated and dissolved is added and further mixed and ground. Next, what melt | dissolved C part was added and mixed sufficiently, and it shape | molded in stick shape. <Part A> Titanium oxide 10.0 wt% Zinc oxide 7.0 Mica 16.0 Red iron oxide 1.5 Yellow iron oxide 1.5 Black iron oxide 1.0 <Part B> Dimethylpolysiloxane (20cs) 29.4 Trimethylolpropane-tri-2-ethylhexanoate 8.0 Liquid paraffin 7.0 p-Dimethylaminobenzoic acid 2-ethylhexyl ester 5.0 2,4,5-Trimethoxycinnamic acid oleyl ester 3.0 Sorbitan Sesquioleate 1.0 Antioxidant 0.1 <part C> Microcrystalline wax 2.0 Ceresin 1.0 Solid paraffin 6.0 Perfume 0.5

Formulation Example 7 (makeup base cream) A makeup base cream was prepared according to the following formulation. The preparation method is such that the oil phase part and the water phase part are each heated and dissolved at 70 ° C., the water phase part is added to the oil phase part to emulsify and disperse, and then cooled,
A makeup base cream was obtained. <Oil phase part> Squalane 19.0 wt% Glyceryl triisostearate 10.0 Isopar G 5.0 Sorbitan sesquioleate 1.0 Polysiloxane Ethylene-modified organopolysiloxane 3.0 p-Methoxycinnamic acid 2-ethylhexyl ester 1.0 2,4,5-Trimethoxycinnamic acid 2-ethylhexyl ester 1.0 Antioxidant Appropriate amount Fragrance Appropriate amount <Water phase part> 1,3-Butylene glycol 5.0 Fine particle titanium oxide 10.0 Antiseptic Agent Appropriate amount Purified water Residual

[0036]

INDUSTRIAL APPLICABILITY The cinnamic acid ester derivative according to the present invention has high solubility in non-polar oils, excellent UV-A absorption ability, and discolors in the presence of metal ions. Never. Therefore, the cinnamic acid ester derivative is used as a UV-A absorber for various skin external preparations, particularly,
It can be blended with a non-polar oil-based external preparation for skin, and it is possible to obtain an external preparation for skin which is excellent in ultraviolet protection effect, water resistance, feeling of use and product stability.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI technical display location C09K 3/00 104 Z

Claims (3)

[Claims] 1. A cinnamic acid ester derivative represented by the following general formula 1. [Chemical 1] (In the formula, R ¹ is a C ₁ -C ₈ alkyl group, and R ² is C ₁ -C ₁₈
Is an alkyl group or an alkenyl group, and n is an integer of 2 to 3. However, the 2,3,4-trialkoxy substitution product and the 3,4,5-trialkoxy substitution product are excluded. ) 2. An ultraviolet absorber comprising one or more of the cinnamic acid ester derivative according to claim 1. 3. A skin external preparation containing one or more kinds of the cinnamic acid ester derivative according to claim 1.