JP2008088126A - Furylmethylene malonamide compound and salt thereof, ultraviolet light absorber and external preparation for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new compound having high water solubility, excellent absorbency in an ultraviolet wavelength region without absorption in a visible region and excellent stability. <P>SOLUTION: The ultraviolet light absorber is composed of a furylmethylene malonamide compound represented by the general formula (1) [wherein, R<SB>1</SB>, R<SB>2</SB>and R<SB>3</SB>represent each independently a hydrogen atom or a 1-4C straight chain or a 1-4C branched alkyl group; R<SB>4</SB>and R<SB>5</SB>represent each ä(CH<SB>2</SB>)<SB>m</SB>-O}<SB>n</SB>-R<SB>6</SB>; and R<SB>6</SB>represents a hydrogen atom or a 1-4C straight chain or a 1-4C branched alkyl group; m is an integer of 2-4: and n is an integer of 1-5] and/or a salt thereof. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a furylmethylenemalonamide compound and a salt thereof, particularly an ultraviolet absorber comprising the compound, an ultraviolet absorbing composition containing the compound as an active ingredient, and a skin external preparation containing the compound.

  Among ultraviolet rays contained in sunlight, ultraviolet rays having a wavelength of 290 nm or less are absorbed by the ozone layer and do not reach the ground surface, but ultraviolet rays of 290 nm to 400 nm reach the ground surface and have various effects. Dermatologically, it is known that medium wavelength ultraviolet rays of 290 nm to 320 nm cause erythema and blister formation, melanogenesis enhancement, pigmentation and the like. In addition, the long wavelength ultraviolet rays of 320 nm to 400 nm have an immediate blackening effect that darkens the skin immediately after irradiation, and the energy reaches the dermis, which also affects the elastic fibers in the blood vessel wall and connective tissue. It is said to affect. These effects of medium to long wavelength ultraviolet rays are considered to promote skin aging and contribute to the formation of spots, freckles, wrinkles and the like.

  In order to protect the skin from such ultraviolet rays, ultraviolet absorbers such as benzotriazole derivatives, benzophenone derivatives, salicylic acid derivatives, paraaminobenzoic acid derivatives, cinnamic acid derivatives, and urocanic acid derivatives have been conventionally used.

  However, these UV absorbers are generally oil soluble and could not be incorporated into aqueous based products. Recently, UV protection is considered important not only in summer bathing and winter skiing, but also in everyday life, and ordinary skin care cosmetics are desired to have UV protection effects. Therefore, it is desired to develop a water-soluble ultraviolet absorber that can be blended in a sufficient amount into a water-based skin care cosmetic such as skin lotion.

  There are few water-soluble ultraviolet absorbers so far, and among those currently used, sodium 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone is known. However, since the substance is a sulfonate, there is a problem in that the pH of the blending system is affected, and the ultraviolet absorption region changes depending on the pH of the blending system. Further, although the substance is water-soluble, its solubility is only about 6% at 25 ° C., and there is a problem that it precipitates at a low temperature when blended in a high concentration in the product. Furthermore, since the substance has absorption even in the visible light region, it is colored pale yellow, which has a drawback of affecting the color tone of the product.

  Furthermore, as a water-soluble ultraviolet absorber, Patent Document 1 discloses a p-aminobenzoic acid amide derivative having a 2-deoxyhexose residue. Patent Document 2 discloses a cinnamic acid amide having a 2-deoxyhexose residue. However, the solubility of these substances in water was low and not fully satisfactory.

On the other hand, UV absorbers are also used in fields other than pharmaceuticals and cosmetics. For example, UV absorbers can be added to various materials such as paints, dyes, pigments, various resins, synthetic rubbers, latexes, films, and fibers. Is used to protect the product itself or a product coated with the coating film or film from ultraviolet rays, to prevent deterioration and alteration due to ultraviolet rays, and to maintain the quality. However, conventional ultraviolet absorbers also have the problem that they sublimate and volatilize by heating during coating film baking or resin molding, or gradually volatilize over time without heating. It was.
In addition, when an ultraviolet absorber is blended with an external preparation for skin, the stability that the compound itself is not decomposed by exposure to sunlight is also important.
JP-A-10-120698 JP 2002-363195 A

  The present invention has been made in view of the above-mentioned circumstances, and its problem is that it is highly water-soluble, has an excellent ultraviolet absorption ability over a wide ultraviolet wavelength region, has no absorption in the visible region, and is stable. An object of the present invention is to provide an excellent compound, an ultraviolet absorber comprising the compound, an ultraviolet absorbing composition containing the compound as an active ingredient, and a skin external preparation containing the compound.

  As a result of intensive studies conducted by the present inventors in order to achieve the above-mentioned problems, a furylmethylenemalonamide compound represented by the following general formula (1) and a salt thereof were synthesized and investigated for properties thereof. The present inventors have found that the compound has excellent ultraviolet absorbing ability over a wide ultraviolet wavelength region, does not absorb in the visible region, and has excellent water solubility and stability, and has completed the present invention.

（式中、Ｒ_１、Ｒ_２、Ｒ_３は各々独立して、水素原子又は炭素数１〜４の直鎖または分岐のアルキル基を表し、Ｒ_４、Ｒ_５は各々｛(ＣＨ_２)_ｍ−Ｏ｝_ｎ−Ｒ_６を表し、Ｒ_６は水素原子または炭素数１〜４の直鎖または分岐のアルキル基アルキル基を表す。ｍは２〜４、ｎは１〜５の整数である。Ｒ_４、Ｒ_５は同一であっても又は異なってもよい。） That is, the first subject of the present invention is to provide a furylmethylenemalonamide compound represented by the following general formula (1) and a salt thereof.

(Wherein R ₁ , R ₂ and R ₃ each independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms, and R ₄ and R ₅ each represent {(CH ₂ ) _{m. -O}} represents n -R _{6, R 6} is .m representing a linear or branched alkyl group the alkyl group having 1 to 4 carbon hydrogen atom or carbon 2 to 4, n is an integer of 1 to 5. R ₄ and R ₅ may be the same or different.)

The second subject of the present invention is to provide an ultraviolet absorber comprising the furylmethylenemalonamide compound of the above general formula (1) and / or a salt thereof.
Furthermore, a third subject of the present invention is to provide an ultraviolet absorbing composition containing the furylmethylenemalonamide compound of the above general formula (1) and / or a salt thereof as an active ingredient.

The fourth subject of the present invention is to provide a skin external preparation having the furylmethylenemalonamide compound of the above general formula (1) and / or a salt thereof.
It is preferable that the skin external preparation further contains an inorganic powder.

The furylmethylenemalonamide compound and salts thereof of the present invention have high ultraviolet absorption ability over a wide ultraviolet wavelength region, and the structure of the compound itself is also excellent in stability, so that it is effective as an ultraviolet absorber having excellent stability. Can be used. Moreover, since this compound is excellent in water solubility, it can be mix | blended with a water-based product. Therefore, by blending the compound, it is possible to obtain a UV-absorbing composition and a skin external preparation excellent in UV-protecting effect and stability.
Further, since the furylmethylenemalonamide compound and its salt of the present invention have no absorption in the visible part, when the compound is blended into a product, it is not colored and changes in appearance over time are observed. Absent.

（式中、Ｒ_１、Ｒ_２、Ｒ_３は各々独立して、水素原子又は炭素数１〜４の直鎖または分岐のアルキル基を表し、Ｒ_４、Ｒ_５は各々｛(ＣＨ_２)_ｍ−Ｏ｝_ｎ−Ｒ_６を表し、Ｒ_６は水素原子または炭素数１〜４の直鎖または分岐のアルキル基を表す。ｍは２〜４、ｎは１〜５の整数である。Ｒ_４、Ｒ_５は同一であっても又は異なってもよい。） The furylmethylenemalonamide compound and its salt of the present invention are represented by the following general formula (1).

(Wherein R ₁ , R ₂ and R ₃ each independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms, and R ₄ and R ₅ each represent {(CH ₂ ) _{m. -O}} represents n -R _{6, R 6} is .m representing a linear or branched alkyl group having 1 to 4 carbon hydrogen atom or carbon 2 to 4, n is an integer of 1 to 5 .R ₄ , R ₅ may be the same or different.)

In the furylmethylenemalonamide compound represented by the general formula (1) and a salt thereof, R ₁ , R ₂ and R ₃ each independently represent a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. To express. Specific examples include methyl, ethyl, propyl, n-butyl, isopropyl group and the like. Among these, R ₁ , R ₂ , and R ₃ are preferably each independently selected from any of a hydrogen atom, a methyl group, and an ethyl group.

In the furylmethylenemalonamide compound represented by the above general formula (1) and a salt thereof according to the present invention, R ₄ and R ₅ each represent {(CH ₂ ) _m —O} _n —R ₆ , R ₆ represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. Examples of the linear or branched alkyl group having 1 to 4 carbon atoms include methyl, ethyl, propyl, n-butyl, isopropyl group and the like. In the present invention, R ₆ is preferably a hydrogen atom. R ₄ and R ₅ may be the same or different.
m is an integer of 2 to 4, and n is an integer of 1 to 5. In the present invention, m is preferably 2, and n is preferably 2.

上記一般式（２）で表される化合物において、式中のＲ_１、Ｒ_２、Ｒ_３は前述と同様の特徴を有する物であり、この範囲においていずれのものであってもよい。 In the present invention, it is particularly preferred that R ₄ and R ₅ are each {(CH ₂ ) ₂ —O} ₂ —H, that is, those represented by the following general formula (2).

In the compound represented by the general formula (2), R ₁ , R ₂ and R ₃ in the formula have the same characteristics as described above, and any of them may be used within this range.

The chemical names of the furylmethylenemalonamide compound represented by the above general formula (1) and the salt thereof according to the present invention vary depending on R ₁ , R ₂ , R ₃ , and R ₄ , but for example, 2- (2- ^{furyl-methylene)} -N 1, ^{N 3} - bis [2- (2-hydroxyethoxy) ethyl] ^{malonamide, N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl] -2 - [(5-methyl 2-furyl) methylene] malonamide, 2-[(5-ethyl-2-furyl) methylene] -N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide, 2-[(4 5-dimethyl-2-furyl) methylene] -N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide and the like. The structures of these compounds correspond to the following compounds (3) to (6) in order. Examples of the compound represented by the general formula (2) include the following compounds (3) to (6).

The furylmethylenemalonamide compound represented by the general formula (1) according to the present invention can be produced using a known synthesis reaction.
Representative examples of the production method are shown below, but the present invention is not limited thereto. Unless otherwise specified in the following production methods, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are as defined in the general formula (1).

<Production method 1>

First, the said manufacturing method 1 is demonstrated. As a first step, 2-furaldehyde (furfural) optionally having a substituent represented by the general formula (7) and a malonic acid ester represented by the general formula (8) (for example, R _{When 7} is an ethyl group, the compound represented by the above formula (9) can be synthesized by a known condensation reaction with diethyl malonate. It is preferable to use about 1 equivalent of the compound of formula (8) in molar ratio to the compound of formula (7).
As a reaction solvent used in this condensation reaction, for example, toluene, benzene, pyridine and the like can be used alone or a mixed solvent thereof can be appropriately selected and used. As the reaction catalyst, for example, piperidine, acetic acid, ammonium acetate and the like can be used alone or in combination. The reaction solvent is preferably used in an amount that provides a concentration in a normal synthesis reaction, and is, for example, a mass ratio of 1 to 50 with respect to the compound (7). Moreover, the addition amount of the reaction catalyst used should just be based on the catalyst amount of a normal reaction, for example, is the quantity of 0.01-0.9 by molar ratio with respect to the compound of Formula (7). The compounds of the formulas (7) and (8) and the reaction catalyst are mixed in a reaction solvent and then refluxed to obtain the compound of the formula (9).

Subsequently, as a second step, the compound of formula (9) is reacted with amine NH ₂ —R ₄ and / or NH ₂ —R ₅ under heating conditions to obtain the target of formula (1). A furylmethylenemalonamide compound can be synthesized. The reaction temperature at this time is preferably 50 to 200 ° C. When R ₄ and R ₅ are the same with respect to the compound of formula (9), it is preferable to use about 2 equivalents of either amine NH ₂ —R ₄ or NH ₂ —R ₅ in molar ratio. When R ₄ and R ₅ are different, it is preferable to first react one of them in a molar ratio of about 1 equivalent and then react the other in a molar ratio of about 1 equivalent.

In addition, the compound of formula (9) is hydrolyzed to obtain a dicarboxylic acid of formula (10), and then amine NH ₂ —R ₄ and / or NH ₂ —R ₅ and a known amide bond formation method can be easily used. It can also be synthesized. That is, the furylmethylenemalonamide compound of the formula (1) is activated by reacting amines NH ₂ -R ₄ and / or NH ₂ -R ₅ with the activated form by activating the carboxyl group. Can be synthesized.
As a method for activating the carboxyl group, the following methods (i) to (iii) can be used.
(I) An active ester method using p-nitrophenyl ester, N-hydroxysuccinimide ester or the like.
(Ii) A mixed acid anhydride method using a mixed acid anhydride with a carbonic acid monoalkyl ester using isobutyloxycarbonyl chloride, ethyloxycarbonyl chloride or the like.
(Iii) Acid chloride method using an acid chloride obtained by reacting with phosphorus trichloride, phosphorus pentachloride, thionyl chloride or the like.

Further, by adding a coupling reagent to a mixed solution of the dicarboxylic acid of the formula (10) and the amine NH ₂ -R ₄ and / or NH ₂ -R ₅ for coupling, furylmethylenemalon of the formula (1) Amide compounds can also be synthesized. As the coupling reagent, N, N′-dicyclohexylcarbodiimide (DCC), N-hydroxysuccinimide and DCC, 1-hydroxybenzotriazole and DCC, or the like can be used.

Moreover, it is also possible to manufacture by the manufacturing method 2 shown below.
<Production method 2>

That is, as the 1 ′ stage, the malonic acid ester represented by the formula (8) is reacted with the amine NH ₂ —R ₄ and / or NH ₂ —R ₅ to synthesize the diamide compound represented by the formula (11). To do. It is also possible to synthesize a diamide compound of formula (11) from malonic acid and amines NH ₂ —R ₄ and / or NH ₂ —R ₅ by a known amide bond formation method. The specific method for producing the amide bond is as described above. When R ₄ and R ₅ are the same with respect to the compound of formula (8), it is preferable to use about 2 equivalents of either amine NH ₂ —R ₄ or NH ₂ —R ₅ in molar ratio. When R ₄ and R ₅ are different, it is preferable to first react one of them in a molar ratio of about 1 equivalent and then react the other in a molar ratio of about 1 equivalent.
Furthermore, as a 2 ′ stage, the diamide compound of formula (11) and 2-furaldehyde (furfural) which may have a substituent are subjected to a known condensation reaction, and the furylmethylenemalonamide compound of formula (1) is converted to It is possible to synthesize. As a reaction solvent used in this condensation reaction, for example, toluene, benzene, pyridine and the like can be used alone or a mixed solvent thereof can be appropriately selected and used. As the reaction catalyst, for example, piperidine, acetic acid, ammonium acetate and the like can be used alone or in combination. The reaction solvent is preferably used in an amount that provides a concentration in a normal synthesis reaction, and is, for example, a mass ratio of 1 to 50 with respect to the compound (7). Moreover, the addition amount of the reaction catalyst used should just be based on the catalyst amount of a normal reaction, for example, is the quantity of 0.01-0.9 by molar ratio with respect to the compound of Formula (7). The compounds of formula (1) are obtained by mixing the compounds of formulas (7) and (11) and the reaction catalyst in a reaction solvent and then refluxing.

  The compounds necessary for the above production method are furfural (manufactured by Tokyo Chemical Industry Co., Ltd.), 5-methyl-2-furaldehyde (manufactured by Tokyo Chemical Industry Co., Ltd.), diethyl malonate (manufactured by Wako Pure Chemical Industries, Ltd.), 2 Commercial products such as-(2-aminoethoxy) ethanol (manufactured by Tokyo Chemical Industry Co., Ltd.) can be used.

  The furylmethylenemalonamide compound of the present invention can be converted into an inorganic salt or an organic salt according to a conventional method. The salt is not particularly limited, and examples of the inorganic salt include hydrochloride, sulfate, phosphate, hydrobromide, sodium salt, potassium salt, magnesium salt, calcium salt, ammonium salt and the like. Organic salts include acetate, lactate, maleate, fumarate, tartrate, citrate, methanesulfonate, p-toluenesulfonate, triethanolamine salt, diethanolamine salt, amino acid salt, etc. Can be mentioned.

The furylmethylenemalonamide compound and / or salt thereof of the present invention is useful as an ultraviolet absorber. Further, a furylmethylenemalonamide compound and / or a salt thereof can be blended as an active ingredient and mixed with other various substances to constitute an ultraviolet absorbing composition.
Moreover, the said ultraviolet absorber and ultraviolet-absorbing composition can be mix | blended with the various products which exhibit an ultraviolet-absorption effect. In particular, it is preferable to blend in an external preparation for skin.
The external preparation for skin containing the furylmethylenemalonamide compound and / or salt thereof of the present invention exhibits an excellent ultraviolet prevention effect, and the ultraviolet absorbent does not decompose even under exposure to sunlight, so that the effect is long-lasting. Stable over. Further, since it does not absorb the visible region, there is no coloring of the product and no change in appearance over time. Such a feature can be said to be an advantageous effect because a change in appearance over time tends to lead to a negative image of the effect that the user sometimes expects. Furthermore, skin trouble does not occur, and it is extremely useful as an external preparation for sunscreen.

In the skin external preparation for sunscreen, in order to enhance the ultraviolet shielding effect, it is desired to use an inorganic powder ultraviolet shielding agent together with an organic compound ultraviolet absorber. Also, makeup powders often contain inorganic powders. However, when an organic ultraviolet absorber is used in combination with inorganic powder, discoloration may occur.
The furylmethylenemalonamide compound and / or salt thereof of the present invention does not cause discoloration even when blended in a skin external preparation together with the inorganic powder, and can be used in combination with the inorganic powder.

The inorganic powder used in the present invention is not particularly limited as long as it is usually blended in cosmetics and pharmaceuticals. For example, talc, kaolin, boron nitride, mica, sericite, muscovite, biotite, phlogopite, synthetic mica, synthetic mica, permiculite, magnesium carbonate, calcium carbonate, anhydrous silicic acid, aluminum silicate, oxidation Aluminum, barium silicate, calcium silicate, magnesium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate, calcined gypsum, calcium phosphate, fluorapatite, hydroxyapatite, ceramic powder, metal soap (myristin In addition to inorganic powders such as zinc oxide, calcium palmitate, and aluminum stearate), titanium dioxide, zinc oxide, iron oxide, iron titanate, carbon, low-order titanium oxide, mango violet, cobalt violet, black oxide , Chromium hydroxide, cobalt titanate, ultramarine, Prussian blue, titanium oxide-coated mica, titanium oxide-coated bismuth oxychloride, titanium oxide-coated talc, colored titanium oxide-coated mica, bismuth oxychloride, and inorganic pigments such as fish scale flake.
In particular, fine particle titanium oxide and fine particle zinc oxide are preferably blended in sunscreen skin preparations such as sunscreen cosmetics.

When the furylmethylenemalonamide compound and / or salt thereof of the present invention is blended with the external preparation for skin, the blending amount may be appropriately determined according to the desired ultraviolet absorbing ability, and is not particularly limited. Usually, it is preferable that it is 0.001-20 mass% with respect to the skin external preparation whole quantity, More preferably, it is 0.01-10 mass%.
Moreover, the compounding quantity of inorganic powder is not limited. It is determined appropriately according to the product of the external preparation for skin, and usually about 0.1 to 99.5 mass% is blended with respect to the total amount of the external preparation for skin. For example, when preparing a skin external preparation for sunscreen, the inorganic powder is preferably blended in an amount of about 0.1 to 30% by mass based on the total amount.

  The product form of the external preparation for skin of the present invention is not particularly limited. For example, skin care cosmetics such as lotion, milky lotion, cream, beauty liquid, self-tanning agent, foundation cosmetics, makeup cosmetics such as foundation, lipstick, face color, eyeliner, hair spray, hair tonic, hair liquid And other cosmetics for scalp and the like.

  In addition to the above essential components, the external preparation for skin according to the present invention can be usually incorporated into cosmetics and pharmaceuticals, for example, liquid oils, solid oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicones. , Anionic surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant, moisturizer, water-soluble polymer compound, thickener, coating agent, sequestering agent, lower alcohol, polyhydric alcohol , Sugars, amino acids, organic amines, pH adjusters, skin nutrients, vitamins, antioxidants, fragrances, powders, coloring materials, water, and the like can be appropriately blended as necessary. In addition, it is also possible to mix | blend ultraviolet absorbers other than a furyl methylene malonamide compound and its salt with the skin external preparation of this invention.

Further, the furylmethylenemalonamide compound and / or salt thereof of the present invention is blended in products other than the skin external preparation, for example, paints, dyes, pigments, various resins, synthetic rubbers, latexes, films, fibers, etc. It is possible to defend. When the furylmethylenemalonamide compound of the present invention and a salt thereof or an ultraviolet absorber are blended in various products, an ultraviolet absorbing composition is prepared by mixing with other raw material compounds or preparing an aqueous solution, It is also possible to mix this.
Since the furylmethylenemalonamide compound and its salt of the present invention are excellent in thermal stability and do not volatilize, the efficacy can be maintained for a long time. The amount of the furylmethylenemalonamide compound and / or salt thereof in various products and ultraviolet absorbing compositions is usually 0.001 to 20% by mass, preferably 0.01 to 10% by mass.

Hereinafter, the present invention will be specifically described with reference to examples. The present invention is not limited to these.
Example 1-1 Synthesis of 2- (2-furylmethylene) -N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide

(1) Synthesis of N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide Diethyl malonate (3.59 mL, 23.78 mmol) and 2- (2-aminoethoxy) ethanol (5.00 g) 4.56 mmol) at 130 ° C. for 6 hours. The mixture was allowed to cool and then concentrated, and the residue was purified by silica gel column chromatography (chloroform / methanol = 20/1) to obtain N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide (6 .58 g, 99% yield).
The obtained compound was identified by ¹ H-NMR (ECP400, manufactured by JEOL). Tetramethylsilane (TMS) was used as an internal standard. Chemical analysis values are as follows.
¹ H-NMR (DMSO-d ₆ , TMS, ppm)
δ: 7.98 (t, J = 4.8 Hz, 2H), 4.49 (t, J = 5.3 Hz, 2H), 3.52-3.48 (m, 4H), 3.44-3 .41 (m, 8H), 3.25-3.17 (m, 4H), 3.05 (s, 2H).

(2) Synthesis of 2- (2-furylmethylene) -N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl ] Toluron (6 mL), furfural (0.15 mL, 1.80 mmol) and piperidine (0.09 mL, 0.90 mmol) were added to malonamide (0.50 g, 1.80 mmol). The reaction was refluxed for 7 hours, allowed to cool and concentrated. The obtained residue was purified by silica gel column chromatography (chloroform / methanol = 25/1) to give 2- (2-furylmethylene) -N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl]. Malonamide was obtained (0.51 g, yield 80%).
The obtained compound was identified by ¹ H-NMR (ECP400, manufactured by JEOL). Tetramethylsilane (TMS) was used as an internal standard. Chemical analysis values are as follows.
¹ H-NMR (DMSO-d ₆ , TMS, ppm)
δ: 8.42 (t, J = 5.8 Hz, 1H), 7.77 (d, J = 1.9 Hz, 1H), 7.53 (t, J = 5.8 Hz, 1H), 7.18 (S, 1H), 6.86 (d, J = 3.4 Hz, 1H), 6.58 (dd, J = 1.9 Hz, J = 3.4 Hz, 1H), 4.50-4.47 ( m, 2H), 3.55-3.31 (m, 16H).

Example 1-2: N ¹ , N ³ Synthesis of bis [2- (2-hydroxyethoxy) ethyl] -2-[(5-methyl-2-furyl) methylene] malonamide

N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide (0.70 g, 2.52 mmol) to toluene (6 mL), furfural (0.25 mL, 2.52 mmol), piperidine (0.04 mL) 0.50 mmol), acetic acid (0.09 mL, 1.51 mmol) was added. The reaction was refluxed for 3 hours, allowed to cool and concentrated. The obtained residue was purified by silica gel column chromatography (chloroform / methanol = 25/1), and N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] -2-[(5-methyl- 2-Furyl) methylene] malonamide was obtained (0.18 g, 19% yield).
The obtained compound was identified by ¹ H-NMR (ECP400, manufactured by JEOL). Tetramethylsilane (TMS) was used as an internal standard. Chemical analysis values are as follows.
¹ H-NMR (DMSO-d ₆ , TMS, ppm)
δ: 8.37 (t, J = 5.8 Hz, 1H), 7.49 (t, J = 5.8 Hz, 1H), 7.13 (s, 1H), 6.77 (d, J = 2) .9 Hz, 1H), 6.22 (d, J = 2.9 Hz, 1H), 4.50-4.48 (m, 2H), 3.56-3.41 (m, 12H), 3.39. -3.30 (m, 4H), 2.29 (s, 3H).

Evaluation 1: Measurement of absorbance in the ultraviolet wavelength region The ultraviolet absorption spectrum (solvent: water, concentration 10 ppm, optical path length 1 cm) of the furylmethylenemalonamide compound of the present invention was measured with a spectrophotometer (V-560 manufactured by JASCO Corporation). It was measured. The results are shown in Table 1 below. As is clear from Table 1, it was confirmed that the furylmethylenemalonamide compound of the present invention has an excellent absorption ability in the ultraviolet wavelength region (290 to 400 nm).

Evaluation 2: Measurement of absorbance in the visible light region Absorbance of 405 nm visible light (solvent: water, optical path length 1 cm) of the furylmethylenemalonamide compound of the present invention was measured with a spectrophotometer (V-560 manufactured by JASCO Corporation). It was measured. Further, as a comparative example, 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone sodium, which is a conventional water-soluble ultraviolet absorber, was also measured in the same manner. The results are shown in Table 2 below.

As is clear from Table 2 above, the furylmethylenemalonamide compound of the present invention does not absorb in the visible region longer than 400 nm. Therefore, the crystals were white and the aqueous solution was colorless and transparent.
On the other hand, since the comparative compound has absorption in the visible region, the crystals are colored light yellow and the aqueous solution is colored yellow, respectively, and the blending amount is limited to avoid coloring the product, and as a result, a sufficient ultraviolet absorption effect is obtained. I can't expect.

Evaluation 3: Solubility in water The solubility of the furylmethylenemalonamide compound of the present invention in water was measured. Moreover, it measured similarly about 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone sodium as a comparative example. The results are shown in Table 3.

  As is apparent from Table 3 above, the furylmethylenemalonamide compound of the present invention is excellent in solubility in water and can be blended at a high concentration. On the other hand, the comparative compound has low water solubility and is difficult to be blended at a high concentration. If blended at a high concentration, it tends to be deposited at low temperature storage. If the blending amount is limited to avoid this, a sufficient ultraviolet absorption effect cannot be expected.

Evaluation 4: Ultraviolet ray prevention effect Using the furylmethylenemalonamide compound of the present invention, a sample was prepared as follows, and an actual test was conducted. The results of the samples are also shown in Table 4 and Table 5 below.
<Preparation of sample>
The following formula (a) lotion and (b) cream were prepared. Examples of the ultraviolet absorber include Example 1-1 of the present invention; 2- (2-furylmethylene) -N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide, and Example 1-2. N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] -2-[(5-methyl-2-furyl) methylene] malonamide) and, as a comparative example, 2-hydroxy, a water-soluble UV absorber Sodium -4-methoxy-5-sulfoxonium benzophenone was used.

(A) Lotion (alcohol phase)
95% ethanol 25.0 mass%
POE (25) hydrogenated castor oil 2.0
Preservative appropriate amount Fragrance appropriate amount (aqueous phase)
UV absorber 1-10
Glycerin 5.0
Sodium hexametaphosphate Appropriate amount Ion exchange water Residue (Production method)
An aqueous phase and an alcohol phase were prepared and mixed.

(B) Cream stearyl alcohol 7.0% by mass
Stearic acid 2.0
Hydrogenated Lanolin 2.0
Squalane 5.0
2-Octyldodecyl alcohol 6.0
POE (25) cetyl ether 3.0
Glycerin monostearate ester 2.0
Propylene glycol 5.0
UV absorber 1-10
Perfume Appropriate amount Sodium bisulfite Appropriate amount Ethylparaben 0.3
Residual ion exchange water
Propylene glycol and an ultraviolet absorber were added to ion-exchanged water and dissolved, and heated to 70 ° C. (water phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C. while stirring well.

<Test method>
An actual use test was conducted at the beach in summer. An equal amount of each sample was applied to the back of the panel. The degree of sunburn after exposure to direct sunlight was evaluated according to the following criteria. In addition, it carried out by 1 group 10 people.
(Criteria)
Remarkable: No or almost no sunburn symptoms were observed.
Effective: Mild sunburn was observed.
Invalid: Severe sunburn was observed.
(Judgment)
A: More than 80% of the subjects are effective or effective.
B: 50% or more and less than 80% of effective or effective subjects.
C: 30% or more and less than 50% of subjects who are highly effective or effective.
D: Remarkable or effective subjects are less than 30%.

  As is apparent from Tables 4 and 5 above, the external preparation for skin containing the furylmethylenemalonamide compound of the present invention has an ultraviolet ray prevention effect superior to that obtained when a conventional water-soluble ultraviolet absorber is added. It was. In addition, no precipitation of the UV absorber was observed even at low temperature storage.

As described above, the furylmethylenemalonamide compound of the present invention is extremely water-soluble and has an excellent absorption ability in the ultraviolet wavelength region.
Moreover, since visible light of 400 nm or more is not absorbed at all, it is white, and since the aqueous solution is colorless and transparent, there is no problem of coloring the product.
Furthermore, since the water solubility is very high, it can be blended in a large amount in the product, and in this case, the problem of precipitation over time does not occur. In addition, the pH of the blending system is not affected. Therefore, the furyl methylene malonamide compound of the present invention is a very useful compound as a water-soluble ultraviolet absorber.
Therefore, the present inventors further examined the effects of skin irritation, photostability, and inorganic powder in order to investigate suitable conditions when the furylmethylenemalonamide compound of the present invention is blended in a skin external preparation. Went.

Evaluation 5: Skin irritation test Using the same sample as the evaluation 4 (the blending amount of the UV absorber is 10% by mass), the test was performed as follows. The results are shown in Table 6 below.
<Test method>
A 24-hour occlusion patch test was conducted with 20 people per group using fin chambers on the forearm flexion side of healthy male and female volunteers, and judged according to the following criteria.
(Criteria)
Degree of skin reaction No score reaction (negative) 0
Mild erythema (false negative) 1
Erythema (weak positive) 2
Erythema + edema (moderate positive) 3
Erythema + Edema + Papules (strongly positive) 4
Large water bubbles (strongest positive) 5
(Judgment)
The average score obtained by dividing the total score of the 20 people by the number of people was determined and determined according to the following criteria.
A: The average score is 0.
B: The average score is greater than 0 and less than 1.
C: The average score is 1 or more and less than 2.
D: The average score is 2 or more.

  As apparent from Table 6 above, it was confirmed that the external preparation for skin containing the furylmethylenemalonamide compound of the present invention had no skin irritation in the patch test and was extremely excellent in safety.

Evaluation 6: Photostability test After exposing the aqueous solution of the furylmethylenemalonamide compound of the present invention to sunlight for 2 weeks (irradiation amount 80 MJ / m ² ), the residual rate and appearance change were examined, and an ultraviolet absorption spectrum (solvent: water) , Concentration of 10 ppm, optical path length of 1 cm) was measured with a spectrophotometer, and an area value was obtained by integrating the range of 290 nm to 400 nm of the ultraviolet absorption spectrum, and compared with that before exposure to sunlight. The results are shown in Table 7 below.
(Judgment)
Changes in the residual ratio and the area value of the ultraviolet absorption spectrum were determined according to the following criteria.
A: 95% or more before sun exposure.
B: 90% or more and less than 95% before sun exposure.
C: 70% or more and less than 90% before sun exposure.
D: Less than 70% before sun exposure.

As is clear from Table 7 above, the furylmethylenemalonamide compound of the present invention was not decomposed by exposure to direct sunlight for a long time as compared with the conventional water-soluble ultraviolet absorber, and showed a very high residual rate.
Further, there was no change in the shape or area of the ultraviolet absorption spectrum, and no coloring or precipitation was observed in the appearance.

Evaluation 7: Stability test when used in combination with an inorganic powder-based UV shielding agent Sunscreen creams were produced according to the following formulation, stored at 50 ° C. for 2 months, and visually observed for discoloration. We examined the stability when combined with systemic UV screening agents. The results are shown in Table 8 below.
"Sunscreen cream"
(1) Ethylcellulose 1.0% by mass
(2) Ethanol 5.0
(3) 2-ethylhexyl succinate 24.0
(4) Titanium dioxide 1.0
(5) Porous silicic acid powder 1.0
(6) Spherical nylon powder 1.0
(7) Talc 1.0
(8) Sericite 1.0
(9) Boron nitride 1.0
(10) Silicone-treated mica 1.0
(11) UV absorber 10.0
(12) Carboxymethylcellulose 1.0
(13) Ion-exchanged water residue (14) Preservative appropriate amount (15) Fragrance appropriate amount <Production method>
After (2) was added to (1) and sufficiently swollen, (3) to (10) were added and mixed by heating to sufficiently disperse and dissolve. This dispersion was kept at 70 ° C., and after uniformly emulsifying with a homomixer while gradually adding the solution prepared by mixing (11) to (15), the mixture was cooled to 30 ° C. while stirring well to obtain a sunscreen cream.

As is clear from Table 8 above, the conventional water-soluble UV absorbers discolored deeply when combined with inorganic powder, but the skin external preparation containing the furylmethylenemalonamide compound of the present invention also used inorganic powder. However, no discoloration was observed.
As described above, the furylmethylenemalonamide compound of the present invention has no skin irritation, is excellent in light stability, and does not cause discoloration even when used in combination with inorganic powder.
Therefore, the ultraviolet absorbent according to the present invention is very useful as an ultraviolet absorbent that can be blended into an external preparation for skin.

Examples of the external preparation for skin of the present invention will be described below, but the present invention is not limited to these examples. In addition, all compounding quantities are shown by the mass%.
Formulation Example 1: Lotion (alcohol phase)
Ethanol 10.0
Oleyl alcohol 0.1
POE (20) sorbitan monolaurate 0.5
POE (15) lauryl ether 0.5
Preservative appropriate amount Fragrance appropriate amount (aqueous phase)
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 10.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Sodium hydroxide 0.4
1,3-butylene glycol 6.0
Glycerin 4.0
4,5-Dimorpholino-3-hydroxypyridazine 0.3
Residual ion exchange water
An aqueous phase and an alcohol phase were prepared and then mixed to obtain the desired lotion.

Formulation example 2: lotion (alcohol phase)
Ethanol 10.0
Oleyl alcohol 0.1
POE (20) sorbitan monolaurate 0.5
POE (15) lauryl ether 0.5
Preservative appropriate amount Fragrance appropriate amount (aqueous phase)
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 5.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Sodium hydroxide 0.4
1,3-butylene glycol 6.0
Glycerin 4.0
Terephthalylidene dicamphulsulfonic acid 1.0
4,5-Dimorpholino-3-hydroxypyridazine 0.3
Residual ion exchange water
An aqueous phase and an alcohol phase were prepared and then mixed to obtain the desired lotion.

Formulation Example 3: Lotion (alcohol phase)
Ethanol 10.0
Paramethoxycinnamic acid 2-ethylhexyl ester 0.5
2-Hydroxy-4-methoxybenzophenone 0.5
4-tert-butyl-4'-methoxydibenzoylmethane 0.5
2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 0.5
POE (20) oleyl ether 0.5
Preservative appropriate amount Fragrance appropriate amount (aqueous phase)
Dipropylene glycol 6.0
Sorbit 4.0
PEG 1500 5.0
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 20.0
Terephthalylidene dicamphulsulfonic acid 1.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Triethanolamine 1.8
Methylcellulose 0.2
Quince Seed 0.1
Residual ion exchange water
Methyl cellulose and quince seeds are mixed and stirred in a portion of ion-exchanged water to prepare a viscous liquid. The remainder of the ion exchange water and other aqueous phase components were mixed and dissolved, and the viscous liquid was added thereto to obtain a uniform aqueous phase. After preparing the alcohol phase, it was added to the aqueous phase to obtain the desired lotion.

Formulation Example 4: Lotion (alcohol phase)
Ethanol 10.0
Paramethoxycinnamic acid 2-ethylhexyl ester 0.5
4-tert-butyl-4'-methoxydibenzoylmethane 0.5
2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 0.5
POE (20) oleyl ether 0.5
Preservative appropriate amount Fragrance appropriate amount (aqueous phase)
Dipropylene glycol 6.0
Sorbit 4.0
PEG 1500 5.0
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 7.0
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 7.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Triethanolamine 1.8
Methylcellulose 0.2
Quince Seed 0.1
Residual ion exchange water
Methyl cellulose and quince seeds are mixed and stirred in a portion of ion-exchanged water to prepare a viscous liquid. The remainder of the ion exchange water and other aqueous phase components were mixed and dissolved, and the viscous liquid was added thereto to obtain a uniform aqueous phase. After preparing the alcohol phase, it was added to the aqueous phase to obtain the desired lotion.

Formulation Example 5: Cream stearic acid 5.0
Stearyl alcohol 4.0
Isopropyl myristate 18.0
Glycerol monostearate 3.0
Paramethoxycinnamic acid 2-ethylhexyl ester 10.0
2-Hydroxy-4-methoxybenzophenone 5.0
4-tert-Butyl-4'-methoxydibenzoylmethane 3.0
2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 5.0
Propylene glycol 10.0
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 5.0
Terephthalylidene dicamphulsulfonic acid 0.5
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Triethanolamine 1.8
4,5-Dimorpholino-3-hydroxypyridazine 0.2
Potassium hydroxide 0.2
Sodium bisulfite 0.01
Preservative Appropriate amount Perfume Appropriate amount Ion-exchanged water Residue
An aqueous phase component was added to ion-exchanged water to dissolve it, and the mixture was heated and maintained at 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase to pre-emulsify it, and the mixture was uniformly emulsified with a homomixer and then cooled to 30 ° C. with stirring to obtain the desired cream.

Formulation Example 6: Cream stearic acid 5.0
Stearyl alcohol 4.0
Isopropyl myristate 18.0
Glycerol monostearate 3.0
Paramethoxycinnamic acid 2-ethylhexyl ester 10.0
2-Hydroxy-4-methoxybenzophenone 5.0
4-tert-Butyl-4'-methoxydibenzoylmethane 3.0
2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 10.0
Propylene glycol 10.0
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 3.0
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 3.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Sodium hydroxide 0.4
Terephthalylidene dicamphulsulfonic acid 0.5
4,5-Dimorpholino-3-hydroxypyridazine 0.2
Potassium hydroxide 0.2
Sodium bisulfite 0.01
Preservative Appropriate amount Perfume Appropriate amount Ion-exchanged water Residue
An aqueous phase component was added to ion-exchanged water to dissolve it, and the mixture was heated and maintained at 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase to pre-emulsify it, and the mixture was uniformly emulsified with a homomixer and then cooled to 30 ° C. with stirring to obtain the desired cream.

Formulation Example 7: Cream stearic acid 6.0
Sorbitan monostearate ester 2.0
POE (20) sorbitan monostearate ester 1.5
Propylene glycol 10.0
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 10.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Sodium hydroxide 0.4
Glycerin trioctanoate 10.0
Squalene 5.0
Sodium bisulfite 0.01
Ethylparaben 0.3
Perfume appropriate amount Ion exchange water Residue
Propylene glycol and 2- (2-furylmethylene) -N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] malonamide, 2-phenylbenzimidazole-5-sulfonic acid, sodium hydroxide in ion-exchanged water And dissolved, heated and kept at 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C. with stirring to obtain the desired cream.

Formulation Example 8: Cream stearic acid 6.0
Sorbitan monostearate ester 2.0
POE (20) sorbitan monostearate ester 1.5
Propylene glycol 10.0
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2- (5-Methyl-2-furyl) methylene] malonamide 5.0
Glycerin trioctanoate 10.0
Squalene 5.0
Sodium bisulfite 0.01
Ethylparaben 0.3
Perfume appropriate amount Ion exchange water Residue
Propylene glycol and N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl] -2-[(5-methyl-2-furyl) methylene] malonamide are added to ion-exchanged water, dissolved, and heated. Maintained at 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C. with stirring to obtain the desired cream.

Formulation Example 9: Latex Stearic Acid 2.5
Cetyl alcohol 1.5
Vaseline 5.0
Liquid paraffin 10.0
POE (10) monooleate 2.0
Paramethoxycinnamic acid 2-ethylhexyl ester 3.0
2-Hydroxy-4-methoxybenzophenone 2.0
4-tert-butyl-4'-methoxydibenzoylmethane 2.0
2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 5.0
PEG 1500 3.0
Triethanolamine 1.0
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 5.0
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 5.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Sodium hydroxide 0.4
Terephthalylidene dicamphulsulfonic acid 0.5
4,5-Dimorpholino-3-hydroxypyridazine 0.1
Sodium bisulfite 0.01
Ethylparaben 0.3
Carboxyvinyl polymer 0.05
Perfume appropriate amount Ion exchange water Residue
Carboxyvinyl polymer was dissolved in a small amount of ion-exchanged water (A phase). The aqueous phase component was added to the remainder of the ion exchange water, dissolved by heating and maintained at 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase for preliminary emulsification, and the A phase was added and uniformly emulsified with a homomixer, and then cooled to 30 ° C. with stirring to obtain the desired emulsion.

Formulation Example 10: Latex Stearic Acid 2.5
Cetyl alcohol 1.5
Vaseline 5.0
Liquid paraffin 10.0
POE (10) monooleate 2.0
Paramethoxycinnamic acid 2-ethylhexyl ester 3.0
2-Hydroxy-4-methoxybenzophenone 2.0
4-tert-butyl-4'-methoxydibenzoylmethane 2.0
2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 5.0
PEG 1500 3.0
Triethanolamine 1.0
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 3.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Triethanolamine 1.8
Terephthalylidene dicamphulsulfonic acid 0.5
4,5-Dimorpholino-3-hydroxypyridazine 0.1
Sodium bisulfite 0.01
Ethylparaben 0.3
Carboxyvinyl polymer 0.05
Perfume appropriate amount Ion exchange water Residue
Carboxyvinyl polymer was dissolved in a small amount of ion-exchanged water (A phase). The aqueous phase component was added, dissolved by heating and kept at 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase for preliminary emulsification, and the A phase was added and uniformly emulsified with a homomixer, and then cooled to 30 ° C. with stirring to obtain the desired emulsion.

Formulation Example 11: Gel 95% ethanol 10.0
Dipropylene glycol 15.0
POE (50) oleyl ether 2.0
Carboxyvinyl polymer 1.0
Sodium hydroxide 0.55
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 1.0
2-Phenylbenzimidazole-5-sulfonic acid 1.0
Methylparaben 0.1
Perfume appropriate amount Ion exchange water Residue
The carboxyvinyl polymer was uniformly dissolved in ion-exchanged water (A phase). POE (50) oleyl ether was dissolved in 95% ethanol and added to Phase A. After adding components other than sodium hydroxide, sodium hydroxide was added to neutralize and thicken to obtain the desired gel.

Formulation Example 12: Gel 95% ethanol 10.0
Dipropylene glycol 15.0
POE (50) oleyl ether 2.0
Carboxyvinyl polymer 1.0
Sodium hydroxide 0.55
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 5.0
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 5.0
2-Phenylbenzimidazole-5-sulfonic acid 1.0
Methylparaben 0.2
Perfume appropriate amount Ion exchange water Residue
The carboxyvinyl polymer was uniformly dissolved in ion-exchanged water (A phase). POE (50) oleyl ether was dissolved in 95% ethanol and added to Phase A. After adding components other than sodium hydroxide, sodium hydroxide was added to neutralize and thicken to obtain the desired gel.

Formulation Example 13: Cosmetic liquid (A phase)
95% ethanol 10.0
Paramethoxycinnamic acid 2-ethylhexyl ester 1.0
2-Hydroxy-4-methoxybenzophenone 0.5
4-tert-butyl-4'-methoxydibenzoylmethane 0.5
2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 0.5
POE (20) Octyldodecanol 1.0
Methylparaben 0.15
Pantothenyl ethyl ether 0.1
(Phase B)
Potassium hydroxide 0.1
(Phase C)
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 10.0
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 10.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Sodium hydroxide 0.4
Glycerin 5.0
Dipropylene glycol 10.0
Terephthalylidene dican full sulfonic acid 2.0
Sodium bisulfite 0.03
Carboxyvinyl polymer 0.2
Residual ion exchange water
A phase and C phase were uniformly dissolved, and A phase was added to C phase to solubilize. Subsequently, the B phase was added and mixed to obtain the desired cosmetic liquid.

Formulation Example 14: Cosmetic liquid (A phase)
95% ethanol 10.0
Paramethoxycinnamic acid 2-ethylhexyl ester 1.0
4-tert-butyl-4'-methoxydibenzoylmethane 0.5
2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 0.5
POE (20) Octyldodecanol 1.0
Methylparaben 0.15
Pantothenyl ethyl ether 0.1
(Phase B)
Potassium hydroxide 0.1
(Phase C)
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 5.0
2-Phenylbenzimidazole-5-sulfonic acid 3.0
Triethanolamine 1.8
Glycerin 5.0
Dipropylene glycol 10.0
Terephthalylidene dicamphorsulfonic acid 3.0
Sodium bisulfite 0.03
Carboxyvinyl polymer 0.2
Residual ion exchange water
A phase and C phase were uniformly dissolved, and A phase was added to C phase to solubilize. Subsequently, the B phase was added and mixed to obtain the desired cosmetic liquid.

Formulation Example 15: Self-tanning emulsion (Part 1)
2-Ethylhexyl 2-cyano-3,3-diphenyl acrylate 5.0
PEG-5 glyceryl stearate 1.0
PEG-60 glycerin stearate 2.0
Cyclomethicone 5.0
Diisopropyl sebacate 5.0
Behenyl alcohol 2.0
Stearyl alcohol 1.0
Hydrogenated palm oil 2.0
Perfume proper amount (part 2)
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 5.0
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 5.0
Dihydroxyacetone 5.0
Dipotassium glycyrrhizinate 0.01
Ethanol 5.0
1,3-butylene glycol 5.0
EDTA-3Na 0.1
Sodium pyrosulfite 0.1
Paraben Appropriate amount Ion exchange water Residue (Production method)
The part 1 uniformly dissolved at 70 ° C. was added to the part 2 uniformly dissolved at 60 ° C. to carry out an emulsification treatment. Then, it cooled and obtained the target self-tanning emulsion.

Formulation Example 16: Pack (Phase A)
Dipropylene glycol 5.0
POE (60) hydrogenated castor oil 5.0
(Phase B)
Olive oil 5.0
Tocopherol acetate 0.2
Ethylparaben 0.2
Fragrance 0.2
(Phase C)
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 0.1
Sodium bisulfite 0.03
Polyvinyl alcohol (saponification degree 90, polymerization degree 2000) 13.0
Ethanol 7.0
Residual ion exchange water
A phase, B phase, and C phase were each dissolved uniformly, and B phase was added to A phase to solubilize. This was then added to Phase C and mixed to obtain the desired pack.

Formulation Example 17: Pack (Phase A)
Dipropylene glycol 5.0
POE (60) hydrogenated castor oil 5.0
(Phase B)
Olive oil 5.0
Tocopherol acetate 0.2
Ethylparaben 0.2
Fragrance 0.2
(Phase C)
2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 0.1
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 0.1
2-Phenylbenzimidazole-5-sulfonic acid 0.3
Triethanolamine 0.18
Sodium bisulfite 0.03
Polyvinyl alcohol (saponification degree 90, polymerization degree 2000) 13.0
Ethanol 7.0
Residual ion exchange water
A phase, B phase, and C phase were each dissolved uniformly, and B phase was added to A phase to solubilize. This was then added to Phase C and mixed to obtain the desired pack.

Formulation Example 18: Emulsion (oil phase)
Stearyl alcohol 1.5
Squalene 2.0
Vaseline 2.5
Deodorized liquid lanolin 1.5
Evening primrose oil 2.0
Isopropyl myristate 5.0
Glycerol monooleate 2.0
2-Ethylhexyl 2-cyano-3,3-diphenyl acrylate 5.0
POE (60) hardened castor reason 2.0
Tocopherol acetate 0.05
Ethylparaben 0.2
Butylparaben 0.1
Perfume appropriate amount (water phase)
^{N 1,} N ³ - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 5.0
4,5-Dimorpholino-3-hydroxypyridazine 0.05
Sodium bisulfite 0.01
Glycerin 5.0
Sodium hyaluronate 0.01
Carboxyvinyl polymer 0.2
Potassium hydroxide 0.2
Residual ion exchange water
The oil phase and the aqueous phase were each dissolved at 70 ° C. The oil phase was added to the aqueous phase, emulsified with an emulsifier, and then cooled to 30 ° C. with a heat exchanger to obtain the desired emulsion.

Formulation Example 19: Solid powdery foundation (1) Talc 15.0
(2) Sericite 10.0
(3) Spherical nylon powder 10.0
(4) Porous silicic acid powder 15.0
(5) Boron nitride 5.0
(6) Titanium dioxide 5.0
(7) Iron oxide 3.0
(8) Zinc stearate 5.0
(9) 2- (2-Furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 1.0
(10) Liquid paraffin residue (11) 2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 1.0
(12) Triisooctanoic acid glycerin 15.0
(13) Sorbitan sesquioleate 1.5
(14) Preservative appropriate amount (15) Fragrance appropriate amount (Manufacturing method)
The components (1) to (8) were mixed and ground. What mixed each component of (9)-(15) was added to this, and was stirred and mixed. This was molded into a container to obtain the desired solid powdery foundation.

Formulation Example 20: Solid powdery foundation (1) Talc 15.0
(2) Sericite 10.0
(3) Spherical nylon powder 10.0
(4) Porous silicic acid powder 15.0
(5) Boron nitride 5.0
(6) Titanium dioxide 5.0
(7) Iron oxide 3.0
(8) Zinc stearate 5.0
(9) N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 1.0
(10) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 1.0
(11) Liquid paraffin residue (12) glycerin triisooctanoate 15.0
(13) Sorbitan sesquioleate 1.5
(14) Preservative appropriate amount (15) Fragrance appropriate amount (Manufacturing method)
The components (1) to (8) were mixed and ground. What mixed each component of (9)-(15) was added to this, and was stirred and mixed. This was molded into a container to obtain the desired solid powdery foundation.

Formulation Example 21: Water-in-oil emulsion foundation (1) Spherical nylon 10.0
(2) Porous silicic acid powder 8.0
(3) Mica titanium 2.0
(4) Silicone-treated sericite 2.0
(5) Silicone-treated mica 12.0
(6) Silicone-treated titanium dioxide 5.0
(7) Silicone-treated iron oxide 2.0
(8) Ion-exchanged water residue (9) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 5.0
(10) Decamethylcyclopentanesiloxane 18.0
(11) Dimethylpolysiloxane 5.0
(12) Squalane 1.0
(13) Polyoxyethylene-modified dimethylpolysiloxane 2.0
(14) Paramethoxycinnamic acid 2-ethylhexyl ester 3.0
(15) 2-hydroxy-4-methoxybenzophenone 1.0
(16) 4-tert-butyl-4′-methoxydibenzoylmethane 0.5
(17) Terephthalylidene dicamphorsulfonic acid 0.5
(18) 2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 0.5
(19) Preservative appropriate amount (20) Fragrance appropriate amount (Manufacturing method)
The components (10) to (20) were uniformly mixed and dissolved. To this, mixed and ground (1) to (7) were added and dispersed. To this dispersion, (9) dissolved in (8) was added and emulsified. This is filled in a container to obtain the desired water-in-oil type emulsion foundation.

Formulation Example 22: Water-in-oil emulsion foundation (1) Spherical nylon 10.0
(2) Porous silicic acid powder 8.0
(3) Mica titanium 2.0
(4) Silicone-treated sericite 2.0
(5) Silicone-treated mica 12.0
(6) Silicone-treated titanium dioxide 5.0
(7) Silicone-treated iron oxide 2.0
(8) Ion-exchanged water residue (9) N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 3.0
(10) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 3.0
(11) Decamethylcyclopentanesiloxane 18.0
(12) Dimethylpolysiloxane 5.0
(13) Squalane 1.0
(14) Polyoxyethylene-modified dimethylpolysiloxane 2.0
(15) Paramethoxycinnamic acid 2-ethylhexyl ester 3.0
(16) 2-hydroxy-4-methoxybenzophenone 1.0
(17) 4-tert-butyl-4′-methoxydibenzoylmethane 0.5
(18) Terephthalylidene dicamphorsulfonic acid 0.5
(19) 2-Ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 0.5
(20) Preservative appropriate amount (21) Fragrance appropriate amount (production method)
The components (11) to (21) were uniformly mixed and dissolved. To this, mixed and ground (1) to (7) were added and dispersed. To this dispersion, (9) and (10) dissolved in (8) were added and emulsified. This was filled in a container to obtain the desired water-in-oil type emulsion foundation.

Formulation example 23: white powder (1) talc remainder (2) sericite 10.0
(3) Spherical nylon powder 10.0
(4) Boron nitride 5.0
(5) Iron oxide 3.0
(6) Magnesium carbonate 5.0
(7) Squalane 3.0
(8) Glycerin triisooctanoate 2.0
(9) Sorbitan sesquioleate 2.0
(10) 2-Ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 0.5
(11) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 0.5
(12) Preservative appropriate amount (13) Fragrance appropriate amount (Manufacturing method)
The components (1) to (6) were mixed and ground. What mixed each component of (7)-(13) was added to this, and was stirred and mixed, and the target white powder was obtained.

Formulation Example 24: Eye Shadow (1) Talc Residue (2) Mica 15.0
(3) Spherical nylon powder 10.0
(4) Boron nitride 5.0
(5) Iron oxide 3.0
(6) Titanium oxide coated mica 5.0
(7) Squalane 3.0
(8) Glycerin triisooctanoate 2.0
(9) Sorbitan sesquioleate 2.0
(10) 2-Ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 1.0
(11) N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 0.3
(12) Preservative appropriate amount (13) Fragrance appropriate amount (Manufacturing method)
The components (1) to (6) were mixed and ground. To this, a mixture of the components (7) to (13) was added and stirred and mixed to obtain the desired eye shadow.

Formulation Example 25: Lipstick (1) Carnauba 0.5
(2) Candelilla wax 5.0
(3) Ceresin 10.0
(4) Squalane residue (5) Glycerol triisostearate 10.0
(6) Glycerin diisostearate 20.0
(7) Terephthalylidene dicamphorsulfonic acid 0.5
(8) Paramethoxycinnamic acid 2-ethylhexyl ester 3.0
(9) 2-Ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 5.0
(10) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 3.0
(11) Macadamia nut oil fatty acid cholesteryl 4.0
(12) Synthetic sodium silicate-magnesium 0.5
(13) Hydrophobic silica 0.5
(14) Ion exchange water 2.0
(15) Colorant appropriate amount (16) Preservative appropriate amount (17) Fragrance appropriate amount
_{(Manufacturing method)}
(12) and (13) were dispersed in (11) heated to 60 ° C., and (10) and (14) were added thereto and stirred sufficiently. This was added to (1) to (9), which had been dissolved by heating separately, and stirred sufficiently. Further, (15) to (17) were added, dispersed and stirred, and then molded to obtain the desired lipstick.

Formulation Example 26: Lipstick (1) Carnauba 0.5
(2) Candelilla wax 5.0
(3) Ceresin 10.0
(4) Squalane residue (5) Glycerol triisostearate 10.0
(6) Glycerin diisostearate 20.0
(7) Terephthalylidene dicamphorsulfonic acid 0.5
(8) Paramethoxycinnamic acid 2-ethylhexyl ester 3.0
(9) 2-Ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 5.0
(10) N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 2.0
(11) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 3.0
(12) 2-Phenylbenzimidazole-5-sulfonic acid 3.0
(13) Sodium hydroxide 0.4
(14) Macadamia nut oil fatty acid phytosteryl 4.0
(15) Synthetic sodium silicate-magnesium 0.5
(16) Hydrophobic silica 0.5
(17) Ion exchange water 2.0
(18) Colorant appropriate amount (19) Preservative appropriate amount (20) Fragrance appropriate amount (Manufacturing method)
(15) and (16) were dispersed in (14) heated to 60 ° C., and (10), (11), (12), (13), and (17) were added thereto and stirred sufficiently. This was added to (1) to (9), which had been separately dissolved by heating, and sufficiently stirred. Further, (18) to (20) were added, dispersed and stirred, and then molded to obtain the desired lipstick.

Formulation Example 27: Hair foam (stock solution formulation)
(1) Acrylic resin alkanolamine liquid (50%) 8.0
(2) Polyoxyethylene hydrogenated castor oil appropriate amount (3) Liquid paraffin 5.0
(4) Glycerin 3.0
(5) Perfume appropriate amount (6) Preservative appropriate amount (7) Ethanol 15.0
(8) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 7.0
(9) Ion exchange water residue (filling formula)
(1) Stock solution 90.0
(2) Liquefied petroleum gas 10.0
(Manufacturing method)
Liquid paraffin was added to a dissolved mixture of glycerin and polyoxyethylene hydrogenated castor oil and uniformly emulsified with a homomixer. This was added to the solution of the other ingredients. For filling, the stock solution was filled in the can, and after the valve was mounted, the gas was filled.

Formulation Example 28: Hair foam (stock solution formulation)
(1) Acrylic resin alkanolamine liquid (50%) 8.0
(2) Polyoxyethylene hydrogenated castor oil appropriate amount (3) Liquid paraffin 5.0
(4) Glycerin 3.0
(5) Perfume appropriate amount (6) Preservative appropriate amount (7) Ethanol 15.0
^{(8) N 1, N 3} - bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 3.0
(9) Ion exchange water residue (filling formula)
(1) Stock solution 90.0
(2) Liquefied petroleum gas 10.0
(Manufacturing method)
Liquid paraffin was added to a dissolved mixture of glycerin and polyoxyethylene hydrogenated castor oil and uniformly emulsified with a homomixer. This was added to the solution of the other ingredients. For filling, the stock solution was filled in the can, and after the valve was mounted, the gas was filled.

Formulation Example 29: Hair Liquid (1) Polyoxypropylene (40) Butyl Ether 20.0
(2) Polyoxyethylene hydrogenated castor oil 1.0
(3) Ethanol 50.0
(4) Perfume appropriate amount (5) Preservative appropriate amount (6) Paramethoxycinnamic acid 2-ethylhexyl ester 2.0
(7) 2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 5.0
(8) Dye appropriate amount (9) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 2.0
(10) Residual ion exchange water (Production method)
(1), (2), (4) to (7) were dissolved in (3) (ethanol phase). (8) and (9) were dissolved in (10) (aqueous phase). The aqueous phase was added to the ethanol phase and filtered through a filter paper to obtain the desired hair liquid.

Formulation Example 30: Hair spray (stock solution formulation)
(1) Acrylic resin alkanolamine liquid (50%) 7.0
(2) Cetyl alcohol 0.1
(3) Silicone oil 0.3
(4) Ethanol residue (5) Perfume appropriate amount (6) N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 1.0
(7) Ion exchange water 3.0
(Filling prescription)
(1) Stock solution 50.0
(2) Liquefied petroleum gas 50.0
(Manufacturing method)
Other components were added to ethanol, dissolved, and filtered. For filling, the stock solution was filled in the can, and after the valve was mounted, the gas was filled.

Formulation Example 31: Hair tonic (1) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 3.0
(2) Hardened castor oil ethylene oxide (40 mol) adduct 2.0
(3) Paramethoxycinnamic acid 2-ethylhexyl ester 3.0
(4) 2-hydroxy-4-methoxybenzophenone 3.0
(5) 4-tert-butyl-4′-methoxydibenzoylmethane 3.0
(6) Terephthalylidene dicamphorsulfonic acid 1.0
(7) 2-ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 5.0
(8) 2-Phenylbenzimidazole-5-sulfonic acid 3.0
(9) Triethanolamine 1.8
(10) Ethanol 60.0
(11) Fragrance appropriate amount (12) Residue of ion-exchanged water (Production method)
(2) to (7) were dissolved in (10) (ethanol phase). (1), (8) and (9) were dissolved in (12) (aqueous phase). The ethanol phase and aqueous phase were mixed and (11) was added to obtain the desired hair tonic.

Formulation Example 32: Hair tonic (1) N ¹ , N ³ -bis [2- (2-hydroxyethoxy) ethyl]
-2-[(5-Methyl-2-furyl) methylene] malonamide 2.0
(2) 2- (2-furylmethylene) -N ¹ , N ³ -bis [2-
(2-Hydroxyethoxy) ethyl] malonamide 2.0
(3) 2-Phenylbenzimidazole-5-sulfonic acid 3.0
(4) Sodium hydroxide 0.4
(5) Hardened castor oil ethylene oxide (40 mol) adduct 2.0
(6) 2-methoxyhexyl ester of paramethoxycinnamic acid 3.0
(7) 2-hydroxy-4-methoxybenzophenone 3.0
(8) 4-tert-butyl-4'-methoxydibenzoylmethane 3.0
(9) 2-Ethylhexyl 2-cyano-3,3-
Diphenyl acrylate 5.0
(10) Ethanol 60.0
(11) Fragrance appropriate amount (12) Residue of ion-exchanged water (Production method)
(5) to (9) were dissolved in (10) (ethanol phase). (1) to (4) were dissolved in (12) (aqueous phase). The ethanol phase and aqueous phase were mixed and (11) was added to obtain the desired hair tonic.

Claims (6)

A furylmethylenemalonamide compound represented by the following general formula (1) and a salt thereof.

(Wherein R ₁ , R ₂ and R ₃ each independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms, and R ₄ and R ₅ each represent {(CH ₂ ) _{m. -O}} represents n -R _{6, R 6} is .m representing a linear or branched alkyl group having 1 to 4 carbon hydrogen atom or carbon 2 to 4, n is an integer of 1 to 5 .R ₄ , R ₅ may be the same or different.) In furyl malonic amide compound and a salt thereof according to claim _1, R 4, _{R 5} are each _{{(CH 2) 2 -O}} 2 -H, furyl methylene represented by the following general formula (2) Malonamide compounds and salts thereof.

(In the formula, R ₁ , R ₂ and R ₃ each independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms.)   An ultraviolet absorber comprising the furylmethylenemalonamide compound according to claim 1 or 2 and / or a salt thereof.   A UV-absorbing composition comprising the furylmethylenemalonamide compound according to claim 1 or 2 and / or a salt thereof as an active ingredient.   A skin external preparation comprising the furylmethylenemalonamide compound and / or a salt thereof according to claim 1 or 2. The skin external preparation according to claim 5, further comprising an inorganic powder.