JP2000319629A - Water-soluble wide-range ultraviolet absorber and ultraviolet absorbing composition and external dermatologic preparation containing same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ultraviolet absorber having a high water solubility, an excellent absorptivity over a wide ultraviolet wavelength region, no absorptions in the visible region, and having high stability and safety by using a pyrimidine derivative or its salt as the principal component. SOLUTION: This absorber consists mainly of a pyrimidine derivative of formula I or its salt. In the formula, R1 is H or a 1-3C alkyl; A is a group of any one of formulae II, III, and IV; and R2 is H, a 1-3C H or an alkyl. Although the absorber can be incorporated in various products, it is desirable to incorporate it in an external dermatologic preparation. An external dermatologic preparation containing this absorber exhibits an excellent ultraviolet intercepting effect, is excellent in product stability because of no tendency to suffer from the deposition of the constituent ultraviolet absorber even when stored at low temperatures, and exhibits its effect stably for a long time because the absorber does not decompose even upon exposure to sunlight.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an ultraviolet absorbing agent, and more particularly to an ultraviolet absorbing agent having high water solubility, having high absorption in a wide range of ultraviolet light, and having no absorption in a visible light region. The present invention relates to an ultraviolet absorbing composition, particularly a skin external preparation, containing

[0002]

2. Description of the Related Art Among ultraviolet rays contained in sunlight, 290
UV light with a wavelength below nm is absorbed by the ozone layer,
Although it does not reach the ground surface, ultraviolet rays of 290 to 400 nm reach the ground surface and have various effects. Skin chemistry is 2
It is known that medium wavelength ultraviolet rays of 90 nm to 320 nm cause erythema and blister formation, increase in melanin formation, pigmentation and the like. In addition, the long-wavelength ultraviolet light having a wavelength of 320 nm to 400 nm has an immediate blackening effect of blackening the skin immediately after irradiation, and its energy reaches the dermis, which also affects the elastic fibers in the blood vessel wall and connective tissue. It is said to exert. The action of these medium to long wavelength ultraviolet rays is believed 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 used.

[0004]

However, these UV absorbers are generally oil-soluble and could not be incorporated into aqueous-based products. Recently, ultraviolet protection is considered to be important not only for use in summer bathing and winter skiing, but also in daily life, and it is desired that ordinary skin care cosmetics have an ultraviolet protection effect.
Therefore, development of a water-soluble ultraviolet absorber which can be incorporated in a large amount into a water-based skin care cosmetic such as a lotion has been desired.
In addition, as an ultraviolet absorber, 290-4
It is desirable to be able to absorb 00 nm ultraviolet rays over a wide wavelength range. Furthermore, when blending an ultraviolet absorber into an external preparation for the skin, of course, there is no skin irritation,
It is also important that UV absorbers are not degraded by sun exposure.

To date, there are almost no water-soluble broad-range ultraviolet absorbers, and sodium 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone is currently used. However, since this substance is a sulfonic acid salt, it exhibits strong acidity and affects the pH of the compounding system. Further, although this substance is water-soluble, its solubility is only about 6% at 25 ° C., and there is a problem that if it is incorporated in a product in a high concentration, it precipitates at a low temperature. further,
Since this substance also absorbs in the visible light region, it is colored pale yellow, and has a drawback of affecting the color tone of the product.

[0006] UV absorbers are also used in fields other than pharmaceuticals and cosmetics. For example, UV absorbers are added to various materials such as paints, dyes, pigments, various resins, synthetic rubbers, latexes, films and fibers to absorb UV rays. And the product itself,
Alternatively, it is used to protect the product coated with the coating film or film from ultraviolet rays, prevent deterioration and deterioration due to ultraviolet rays, and maintain quality. However, conventional UV absorbers also have a problem in that they are sublimated and volatilized by heating at the time of baking of a coating film or molding of a resin, or are gradually volatilized with time without heating, and the effect is reduced. Was.

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned problems of the prior art. One of the objects of the present invention is to have high water-solubility, excellent absorption ability over a wide ultraviolet wavelength range, and visible light range. Is to provide an ultraviolet absorber having no absorption, high stability and high safety, and one is to provide an ultraviolet absorbent composition containing the ultraviolet absorber, especially a skin external preparation. is there.

[0008]

Means for Solving the Problems In order to achieve the above object, the present inventors have conducted intensive studies and as a result, certain pyrimidine derivatives have the above-mentioned properties, and have a water-soluble broad ultraviolet absorption. It was found that the composition was very excellent as an agent, and the present invention was completed. That is, the ultraviolet absorbent according to the present invention comprises the following pyrimidine derivative (1)
As a main component.

[0009]

Embedded image (In the general formula (1), R ¹ represents hydrogen or an alkyl group having 1 to 3 carbon atoms. A is any of the following groups (2a) to (2c).)

[0010]

Embedded image

Embedded image (In the general formula (2b), R ² is a hydrogen atom or a group having 1 to 3 carbon atoms.
Means an alkyl group. )

Embedded image

In the present invention, R ¹ is preferably a methyl group. In the present invention, A is preferably the group (2a). In the present invention, A is preferably the group (2b), and more preferably R ² is a hydrogen atom. Also,
In the present invention, A is preferably the group (2c). An ultraviolet absorbing composition according to the present invention contains the ultraviolet absorbing agent according to any of the above. The skin external preparation according to the present invention is characterized by containing the ultraviolet absorbent described in any of the above. Further, the external preparation for skin according to the present invention is characterized by further containing an inorganic powder. Further, a skin external preparation for sunscreen according to the present invention is characterized by comprising any of the above-mentioned skin external preparations. Further, the skin care cosmetic for sunscreen according to the present invention is characterized by comprising any of the above-mentioned external preparations for skin. Further, the makeup cosmetic according to the present invention is characterized by comprising any of the above-mentioned external preparations for skin.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION In the pyrimidine derivative (1), R ¹ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, such as methyl, ethyl, n-propyl, or isopropyl. Group. In the group (2b), R ² is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and is preferably a hydrogen atom. The pyrimidine derivative (1) can be a compound (1 ′) which is a tautomer thereof under certain conditions by the following equilibrium.

[0013]

Embedded image In the present invention, only the pyrimidine derivative (1) is described for convenience, but the compound (1 ′) or a mixture thereof may be used.

The pyrimidine derivative (1) is specifically illustrated below. 2-amino-4-methyl-6- (1-piperazinyl) pyrimidine-3-oxide, 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide, 2-amino-4-methyl-6-thiomorpholino Pyrimidine-3-oxide, 2-amino-4-ethyl-6
-(1-piperazinyl) pyrimidine-3-oxide, 2-amino-4
-Ethyl-6-morpholinopyrimidine-3-oxide, 2-amino-4-ethyl-6-thiomorpholinopyrimidine-3-oxide,

2-amino-4-n-propyl-6- (1-piperazinyl) pyrimidine-3-oxide, 2-amino-4-n-propyl-6-
Morpholinopyrimidine-3-oxide, 2-amino-4-n-propyl-6-thiomorpholinopyrimidine-3-oxide, 2-amino-4-iso-propyl-6- (1-piperazinyl) pyrimidine-3-
Oxides, 2-amino-4-iso-propyl-6-morpholinopyrimidine-3-oxide, 2-amino-4-iso-propyl-6-thiomorpholinopyrimidine-3-oxide and the like.

The pyrimidine derivative (1) can be synthesized by a known method. The typical production method is shown below.

Embedded image

In the above reaction formula, A and R ¹ are as defined above, and B represents a bromine atom or a chlorine atom.
Compound (3) or compound (4) is ALDRICH
, SIGMA, Tokyo Chemical Industry Co., Ltd., etc., and can be easily obtained. Compound (3) can be converted to compound (4) by treating it with a halogenating agent such as phosphorus oxychloride, phosphorus chloride or phosphorus bromide. Compound (4) is peracetic acid, succinic acid, perpropionic acid,
Compound (5) can be obtained by treating with a peracid such as pertrifluoroacetic acid, perbenzoic acid, or m-chloroperbenzoic acid. Compound (5) is a cyclic amine corresponding to A,
That is, the pyrimidine derivative (1) can be obtained by treating with piperazine, N-lower alkylpiperazine, morpholine, or thiomorpholine.

The pyrimidine derivative (1) can be converted into an inorganic acid salt or an organic acid salt by a known method. Examples of the inorganic acid include hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and the like. Organic acids include acetic acid, lactic acid, maleic acid,
Fumaric acid, tartaric acid, citric acid, methanesulfonic acid, p-toluenesulfonic acid and the like. Of these, the hydrochloride is preferred.

JP-A-2-160710 discloses pyrimidine derivatives having a hair-growth effect as 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide and 2-amino-4.
-Methyl-6- [1- (4-methylpiperazinyl)] pyrimidine-3-
Oxides and the like are described. However, there is no description about the water solubility, ultraviolet absorption effect, light stability, and the like of the pyrimidine derivative, and there is no disclosure at all about the incorporation of the pyrimidine derivative into a skin external preparation as a water-soluble wide-area ultraviolet absorber. Also, Japanese Patent Publication No. 45-25508 discloses a method for producing a pyrimidine derivative (1).
There is no disclosure of water solubility, ultraviolet absorption effect, light stability, skin irritation, formulation into a skin external preparation, and the like.

The ultraviolet absorber containing the pyrimidine derivative (1) or a salt thereof as a main component can be blended in various products, but is preferably blended in a skin external preparation. The external preparation for skin containing the ultraviolet absorbent according to the present invention exhibits an excellent ultraviolet ray preventing effect, and does not precipitate out during storage at low temperatures, and is excellent in product stability. And
Because the UV absorber does not decompose even under sunlight exposure,
The effect is stably exhibited for a long time. Also,
No skin problems. Therefore, it is particularly useful as a skin external preparation for sunscreen.

In addition, in skin external preparations for sunscreens, it is desirable to use an inorganic powder-based ultraviolet shielding agent together with an organic compound-based ultraviolet absorbing agent in order to enhance the ultraviolet shielding effect. In addition, inorganic powders are often blended in makeup cosmetics. However,
When an organic ultraviolet absorber is used in combination with an inorganic powder, discoloration may occur. The ultraviolet absorber of the present invention does not cause discoloration even when blended in a skin external preparation together with the inorganic powder, and thus can be used in combination with the inorganic powder.

The inorganic powder is not particularly limited as long as it is usually used in cosmetics and pharmaceuticals.
For example, talc, kaolin, boron nitride, mica, sericite, sericite, biotite, phlogopite, synthetic mica,
Synthetic mica, permiculite, magnesium carbonate, calcium carbonate, silicic anhydride, aluminum silicate, aluminum oxide, barium silicate, calcium silicate, magnesium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined sulfuric acid Calcium, calcined gypsum, calcium phosphate, fluorapatite, hydroxyapatite, ceramic powder, metal soap (zinc myristate, calcium palmitate,
In addition to inorganic powders such as aluminum stearate), titanium dioxide, zinc oxide, iron oxide, iron titanate, carbon,
Low order titanium oxide, mango violet, cobalt violet, chromium oxide, chromium hydroxide, cobalt titanate, ultramarine, navy blue, titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, colored titanium oxide coated mica, oxy Examples include inorganic pigments such as bismuth chloride and fish scale foil.

The form of the external preparation for skin of the present invention is not particularly limited as long as the effect of the present invention is exhibited. For example, in addition to skin care cosmetics such as lotion, milky lotion, cream, and beauty serum, makeup cosmetics such as base makeup, foundation, lipstick, face color, eyeliner, and the like can be mentioned. In the present invention, a skin external preparation is
Does not include hair cosmetics for the scalp or hair. When the ultraviolet absorbent of the present invention is incorporated into a skin external preparation, the amount of the ultraviolet absorbent may be appropriately determined depending on the intended ultraviolet absorbing ability, but is usually 0.001 to 20% by weight, preferably 0 to 20% by weight in the composition. 0.01 to 10% by weight.

The external preparation for skin of the present invention contains, in addition to the above essential components, components that can be generally incorporated into cosmetics and pharmaceuticals, for example,
Liquid fats, solid fats, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicones, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, humectants, high water solubility Molecular compounds, thickeners, coating agents, sequestering agents, lower alcohols, polyhydric alcohols, sugars, amino acids, organic amines, pH adjusters, skin nutrition agents, vitamins, antioxidants, flavors, powders, A coloring material, water and the like can be appropriately compounded as needed. Further, an ultraviolet absorber other than the pyrimidine derivative (1) can be blended.

The ultraviolet absorbent according to the present invention is also incorporated into products other than the external preparation for the skin, for example, paints, dyes, pigments, various resins, synthetic rubbers, latexes, films, fibers and the like for protection against ultraviolet rays. It is possible. The pyrimidine derivative according to the present invention has excellent thermal stability and does not volatilize, so that its efficacy can be maintained for a long time. In this case, the amount is usually 0.001 to 20% by weight, preferably 0.01 to 10% by weight. Hereinafter, the present invention will be described specifically with reference to examples. Note that the present invention is not limited to these.

Production Example 1 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide 2-amino-4-chloro-6-methylpyrimidine (25 g, 0.174 mol
l) was dissolved in ethanol (800 ml), and m-chloroperbenzoic acid (50.5 g, purity 70%, 0.204 mol) was added under ice-cooling and stirring.
The mixture was further stirred on ice for 8 hours. The precipitated crystals are filtered,
Amino-4-chloro-6-methylpyrimidine-1-oxide (21.
(7 g, yield 79%) as white crystals.

2-amino-4-chloro-6-methylpyrimidine-1
-Oxide (10.0 g, 0.062 mol) was added to morpholine (150 ml) with stirring at room temperature, and the mixture was further stirred at room temperature for 2 hours.
The precipitated crystals were filtered to obtain white crystals of 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide (8.76 g, yield 66%). The chemical analysis values of the obtained compound are as follows.

[0028] ¹ H-NMR (DMSO-d ₆ , TMS, ppm) δ: 2.26 (s, 3H: -CH ₃ ),
3.43 (dd, 4H, J = 4.4 & 5.4Hz: -CH ₂ -N-CH _2- ), 3.64 (dd, 4H,
J = 4.4 & 5.4Hz: -CH ₂ -O-CH _2- ), 6.21 (s, 1H: pyrimidine ring C-5), 7.15 (bs, 2H: NH ₂ ).

[0029]¹³H-NMR: (D_TwoO, dioxane, ppm) δ: 18.1
(-CH_Three), 45.0 (-CH_Two-N-CH_Two-), 66.8 (-CH _Two-O-CH_Two-), 94.6
(Primic ring C-5), 153.8 (Primic ring C-2), 155.9 (Primic ring
Ring C-4), 156.9 (Primicin ring C-6). MS spectrum: MW = 210 (C₉H₁₄N_FourO_Two= 210.24)

Test Example 1 Absorbance UV absorption spectrum of 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide (Preparation Example 1) (solvent: water, concentration: 10 ppm, common path length: 1 cm) and visible light of 405 nm Absorbance (solvent: water, common path length: 1 cm) was measured with a spectrophotometer (Ubest-55, manufactured by JASCO Corporation). In addition, as a comparative compound, sodium 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone was measured in the same manner. The results are shown in FIG.

From these, the pyrimidine derivative of Production Example 1 has broad and strong absorption in the ultraviolet region of 290 to 360 nm, and shows no absorption 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 also has an absorption in the visible region, the crystals are colored pale yellow and the aqueous solution is colored yellow, and the use is limited in terms of coloring the product.

[0032]

[Table 1] UV absorber concentration (wt%) Absorbance  Production Example 1 400 0 100.10  Comparative compound 6 1.99 1 0.320.1 0.06

Test Example 2 Water solubility The solubility of Production Example 1 and the comparative compound in water at 25 ° C. was examined. As a result, the solubility of the pyrimidine derivative of Production Example 1 was 41% by weight, and the solubility of the comparative compound was 6% by weight.
Met. Therefore, the pyrimidine derivative according to the present invention has a very high water solubility and can be blended at a high concentration. Further, since the compound is stably dissolved even at a low temperature, the problem of precipitation of the ultraviolet absorber at a low temperature does not occur even when it is 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, and if it is blended at a high concentration, it may precipitate during low-temperature storage. Therefore, its use is also restricted in terms of product stability.

Test Example 3 UV Prevention Effect (i) Test Method A practical use test was conducted at the seaside in summer. An equal amount of the sample was applied to each of the left and right halves of the back of the panel. The degree of sunburn after exposure to direct sunlight was evaluated according to the following criteria. The test was performed by 20 people in one group.

(Evaluation criteria) Significant effect: No or almost no sunburn symptoms were observed. Effective: Mild sunburn symptoms were observed. Ineffective: Severe tanning was observed. (Judgment) ：: Excellent or effective subjects were 80% or more. Good: 50% or more and less than 80% of the subjects were extremely effective or effective. Δ: Excellent or effective subjects were 30% or more and less than 50%. X: Less than 30% of the subjects were extremely effective or effective.

(Ii) Preparation of sample (a) lotion (alcohol phase) 95% ethanol 25.0% by weight POE (25) hydrogenated castor oil 2.0 preservatives appropriate amount perfume appropriate amount (aqueous phase) Table 2) 0-10 Glycerin 5.0 Sodium hexametaphosphate Appropriate amount Ion-exchanged water Residue (Preparation method) The aqueous phase and the alcohol phase were prepared and mixed.

(B) Cream stearyl alcohol 7.0% by weight stearic acid 2.0 hydrogenated lanolin 2.0 squalane 5.0 2-octyldodecyl alcohol 6.0 POE (25) cetyl ether 3.0 glycerin monostearic acid Ester 2.0 Propylene glycol 5.0 Ultraviolet absorber (described in Table 3) 0-10 Perfume Appropriate amount Sodium bisulfite 0.03 Ethyl paraben 0.3 Ion-exchanged water Residue The absorbent was added and dissolved, and heated to 70 ° C. (aqueous phase). The other components were mixed, melted by heating and kept at 70 ° C. (oil phase). Add the oil phase to the water phase, pre-emulsify, homogenize with a homomixer, and stir well at 30 ° C.
Cooled down.

(Iii) Result

[Table 2](a) Lotion UV absorber content UV protection effect Appearance  2-amino-4-methyl-6-10 ◎ colorless and transparent Morpholino-Primidin-3-oxyto 5 ◎ colorless and transparent1 ◎ colorless and transparent  2-Amino-4-methyl-6-10 ◎ colorless and transparent thiomorpholino-perimidicin-3-oxyto 5 ◎ colorless and transparent1 ◎ colorless and transparent  2-Amino-4-methyl-6- (1-diperacidinyl) 10 ◎ Colorless and transparent Polyimidin-3-oxyto 5 ◎ Colorless and transparent1 ◎ colorless and transparent  2-human peroxy-4-methoxy-5-sulfoxonium 10-* not dissolved benzosophenone sodium 5 △ yellow transparent **1 △ transparent yellow No blending-× colorless and transparent  * Not measured because the UV absorber did not dissolve. ** Crystals precipitate at low temperature storage.

[0039]

[Table 3](b) Cream UV absorber content UV protection effect Appearance  2-amino-4-methyl-6-10 ◎ white morpholino-perimidicin-3-oxyto 5 ◎ white1 ◎ White  2-Amino-4-methyl-6-10 ◎ white thiomorpholino-perimidicin-3-oxyto 5 ◎ white1 ◎ White  2-Amino-4-methyl-6- (1-diperazinyl) 10 ◎ white perimidin-3-oxyto 5 ◎ white1 ◎ White  2-human peroxy-4-methoxy-5-sulfoxonium 10- * Not dissolved Benzodiphenone sodium 5 △ White **1 △ White No blending-× White  * Not measured because the UV absorber did not dissolve. ** Crystals precipitate at low temperature storage.

As is clear from Tables 2 and 3, the external preparation for skin containing the ultraviolet absorbent according to the present invention had a superior ultraviolet ray preventing effect as compared with the case where the conventional water-soluble ultraviolet absorbent was blended. . Also, no precipitation of the ultraviolet absorber was observed at all during storage at low temperature.

As described above, the pyrimidine derivative according to the present invention has extremely high water solubility and has excellent absorption ability over a wide range of ultraviolet rays. Further, since visible light having a wavelength of 400 nm or more is not absorbed at all, it is white, and its aqueous solution is colorless and transparent, so that there is no problem of coloring the product. Further, since it has a very high water solubility, it can be incorporated in a large amount in a product, and in this case, there is no problem of precipitation with time. Also, it does not affect the pH of the compounding system. Therefore, it is very excellent as a water-soluble wide-area ultraviolet absorber. Therefore, in order to examine whether or not the pyrimidine derivative of the present invention can be blended into an external preparation for skin as an ultraviolet absorber, the skin irritation, light stability, and the influence of inorganic powder were further examined.

Test Example 4 Skin irritation test Same sample as in Test Example 3 (the blending amount of the ultraviolet absorber was 10%)
This was performed using (I) Continuous use test A continuous use test by healthy subjects was performed by 20 persons per group. An appropriate amount of each sample was applied to the face twice a day for 4 weeks, and evaluated according to the following criteria.

[0043]

(Judgment) An average score was determined and judged according to the following criteria. A: Average score is 0. ：: Average score is greater than 0 and less than 1. Δ: Average score is 1 or more and less than 2. X: The average score is 2 or more.

(Result)

[Table 4] UV absorber dosage form judgment  2-amino-4-methyl-6- lotion ◎Morpholino-3-imidoxy-3-oxyto cream ◎  2-amino-4-methyl-6- lotion ◎Thiomorpholino-Primicin-3-oxyto cream ◎  2-Amino-4-methyl-6- (1-diperazinyl) lotion ◎Hirimishin-3-oxyto cream ◎  No blending lotion ◎Cream ◎

(Ii) Patch Test A healthy male and female volunteer was subjected to a 24-hour occlusion patch test using a fin chamber on the flexion side of the forearm of 20 volunteers per group, and the results were determined according to the following criteria.

[0047]

(Judgment) The average score was determined and judged according to the following criteria. A: Average score is 0. ：: Average score is greater than 0 and less than 1. Δ: Average score is 1 or more and less than 2. X: The average score is 2 or more.

(Result)

[Table 5] UV absorber dosage form judgment  2-amino-4-methyl-6- lotion ◎Morpholino-3-imidoxy-3-oxyto cream ◎  2-amino-4-methyl-6- lotion ◎Thiomorpholino-Primicin-3-oxyto cream ◎  2-Amino-4-methyl-6- (1-diperazinyl) lotion ◎Hirimishin-3-oxyto cream ◎  No blending lotion ◎Cream ◎

As is clear from Tables 4 and 5, it was confirmed that the skin external preparation containing the ultraviolet absorbent of the present invention had no skin irritation in continuous use tests and patch tests, and was extremely excellent in safety. Was done.

Test Example 5 Light Stability Test After exposing an aqueous solution of the pyrimidine derivative of the present invention to sunlight for 2 weeks (exposure to solar radiation of 80 MJ / m ² ), the residual ratio and changes in appearance were examined, and the ultraviolet absorption spectrum (solvent: water) was examined. ,
A concentration of 10 ppm and an optical path length of 1 cm) were measured with a spectrophotometer, and the area value was determined by integrating the range of 290 to 400 nm of the ultraviolet absorption spectrum, and was compared with that before sunlight exposure.

(Judgment) The residual ratio and the change in the area value of the ultraviolet absorption spectrum were judged according to the following criteria. ：: 95% or more before exposure to sunlight. ：: 90% or more and less than 95% before sun exposure. Δ: 70% or more and less than 90% before sun exposure. X: Less than 70% before sun exposure.

(Result)

[Table 6]  UV absorber Residual rate Appearance UV absorption spectrumOf area value of  2-Amino-4-methyl-6- ◎ colorless and transparent ◎Morpholino phosphoric acid-3-oxytoxin  2-Amino-4-methyl-6- ◎ colorless and transparent ◎Thiomorpholino phosphoric acid 3-oxytoxin  2-Amino-4-methyl-6- (1-diperazinyl) ◎ colorless and transparent ◎Perimisin-3-oxytoxin  2-human peroxy-4-methoxy-5-sulfoxonium ○ transparent yellow ○Hensophenone sodium 

As shown in Table 6, the pyrimidine derivative of the present invention was not decomposed by prolonged exposure to direct sunlight, and showed a very high residual ratio. In addition, there was no change in the shape or area value of the ultraviolet absorption spectrum, and no coloring or precipitation was observed in the appearance.

Test Example 7 Stability test when used in combination with an inorganic powder type ultraviolet ray shielding agent A sunscreen cream was prepared according to the following formulation, and these were stored at 50 ° C. for 2 months, and the discoloration was visually observed. The stability when used in combination with an inorganic powder-based ultraviolet shielding agent was studied.

(Prescription) Sunscreen cream (1) 1.0% by weight of ethyl cellulose (2) Ethanol 5.0 (3) 2-Ethylhexyl succinate 24.0 (4) Titanium dioxide 1.0 (5) Porous anhydrous 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) Siliconized mica 1.0 (11) Carboxymethylcellulose 1.0 (12) UV absorber (described in Table 7) 10.0 (13) Ion-exchanged water residue (14) Preservative appropriate amount (15) Perfume appropriate amount

(Production method) After adding (2) to (1) and sufficiently swelling, (3) to
(10) was 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 a solution in which (11) to (15) were mixed, the mixture was cooled to 30 ° C. with good stirring to obtain a sunscreen cream.

(Result)

[Table 7] UV absorber discoloration  2-amino-4-methyl-6- NoneMorpholino phosphoric acid-3-oxytoxin  2-amino-4-methyl-6- NoneThiomorpholino phosphoric acid 3-oxytoxin  2-Amino-4-methyl-6- (1-hydroxyperazine) NonePerimisin-3-oxytoxin  2-human peroxy-4-methoxy-5-sulfoxonium discolored to deep yellowHensophenone sodium 

As shown in Table 7, 2-hydroxy-4-methoxy-
In the case of sodium 5-sulfoxonium benzophenone, the yellow color changed deeply when inorganic powder was used in combination, but no color change was observed in the case of the pyrimidine derivative of the present invention. As described above, the pyrimidine derivative according to the present invention has no skin irritation, is excellent in light stability, and does not cause discoloration when used in combination with inorganic powder. Therefore, the pyrimidine derivative of the present invention is very useful as an ultraviolet absorber that can be blended in an external preparation for skin.

[0060]

The following are examples of the external preparation for skin according to the present invention, but the present invention is not limited to these examples.
In addition, all compounding amounts are shown by weight%. 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 proper amount Perfume proper amount (aqueous phase) 1 , 3-Butylene glycol 6.0 Glycerin 4.0 2-Amino-4-methyl-6-morpholinopyrimidine-3-oxide 20.0 Ion-exchanged water Residue (Preparation method) Mix water after preparing aqueous phase and alcohol phase, respectively. did.

Example 2 Lotion (Alcohol Phase) Ethanol 10.0 POE (20) Oleyl Ether 0.5 Preservatives Appropriate Amount Perfume Appropriate (Aqueous Phase) Dipropylene Glycol 6.0 Sorbit 4.0 PEG 1500 5.0 2-Amino-4-methyl-6-morpholinopyrimidine-3-oxide 0.001 Methylcellulose 0.2 Quinsseed 0.1 Ion-exchanged water Residue (Preparation method) After stirring, a viscous liquid was prepared. The remaining portion of the ion-exchanged water and other aqueous phase components were mixed and dissolved, and the above-mentioned viscous liquid was added thereto to obtain a uniform aqueous phase. After preparation of the alcohol phase, it was added to the aqueous phase and mixed.

Example 3 Cream Stearic Acid 5.0 Stearyl Alcohol 4.0 Isopropyl Myristate 18.0 Glycerin Monostearate 3.0 Propylene Glycol 10.0 2-Amino-4-methyl-6-morpholinopyrimidine-3 -Oxide 20.0 Potassium hydroxide 0.2 Sodium bisulfite 0.01 Preservatives Appropriate amount Perfume Appropriate amount Ion-exchange water residue (Production method) Propylene glycol, 2-amino-4-methyl-6-morpholino in ion-exchange water Pyrimidine-3-oxide and potassium hydroxide were added to dissolve and heated to 70 ° C. (aqueous phase). The other components were mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase was gradually added to the water phase for pre-emulsification, and after uniform emulsification with a homomixer, the mixture was cooled to 30 ° C. with good stirring.

Example 4 Cream Stearic Acid 6.0 Sorbitan Monostearate 2.0 POE (20) Sorbitan Monostearate 1.5 Propylene Glycol 10.0 2-Amino-4-methyl-6-morpholinopyrimidine- 3-Oxide 1.0 Glycerin trioctanoate 10.0 Squalene 5.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchange water residue (Production method) Propylene glycol and 2-amino acid in ion-exchange water -4-Methyl-6-morpholinopyrimidine-3-oxide was added and dissolved, heated and maintained at 70 ° C. (aqueous phase). The other components were mixed, melted by heating and kept at 70 ° C. (oil phase).
The oil phase was gradually added to the water phase, pre-emulsified, uniformly emulsified with a homomixer, and then cooled to 30 ° C. with good stirring.

Example 5 Emulsion Stearic acid 2.5 Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 POE (10) monooleate 2.0 PEG 1500 3.0 Triethanolamine 1.0 2-amino -4-Methyl-6-morpholinopyrimidine-3-oxide 10.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Carboxyvinyl polymer 0.05 Perfume Appropriate amount Ion-exchange water residue (Preparation method) To a small amount of ion-exchange water The carboxyvinyl polymer was dissolved (phase A). PEG1 in the rest of the ion exchange water
500, 2-amino-4-methyl-6-morpholinopyrimidine-3
-Oxide and triethanolamine were added, and the mixture was dissolved by heating and kept at 70 ° C (aqueous phase). The other components were mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase was added to the water phase to carry out preliminary emulsification, the phase A was added, and the mixture was uniformly emulsified with a homomixer.

Example 6 Gel 95% Ethanol 10.0 Dipropylene Glycol 15.0 POE (50) Oleyl Ether 2.0 Carboxyvinyl Polymer 1.0 Sodium Hydroxide 0.15 2-Amino-4-methyl-6- Morpholinopyrimidine-3-oxide 2.0 Methylparaben 0.2 Perfume Appropriate amount Ion-exchange water residue (Preparation method) A carboxyvinyl polymer was uniformly dissolved in ion-exchange water (A phase). 2-amino-4 in 95% ethanol
-Methyl-6-morpholinopyrimidine-3-oxide and POE (5
0) Oleyl ether was dissolved and added to phase A. After adding components other than sodium hydroxide, sodium hydroxide was added to neutralize and thicken.

Example 7 Essence (phase A) 95% ethanol 10.0 POE (20) octyldodecanol 1.0 methyl paraben 0.15 pantothenyl ethyl ether 0.1 2-amino-4-methyl-6-morpholino Pyrimidine-3-oxide 0.2 (B phase) Potassium hydroxide 0.1 (C phase) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 Ion exchange water Residue ( Production method) Dissolve A phase and C phase uniformly, and add A to C phase
The phases were added and solubilized. Then phase B was added and mixed.

Example 8 Pack (Phase A) Dipropylene Glycol 5.0 POE (60) Hardened Castor Oil 5.0 (Phase B) Olive Oil 5.0 Tocopherol Acetate 0.2 Ethyl Paraben 0.2 Perfume 0.2 ( C-phase) 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide 3.0 sodium bisulfite 0.03 polyvinyl alcohol (degree of saponification, degree of polymerization 2000) 13.0 ethanol 7.0 ion-exchanged water Residue (Preparation method) A phase, B phase, and C phase are each dissolved homogeneously.
Phase B was added to solubilize. This was then added to phase C and mixed.

Each of the above Examples 1 to 7 had an excellent ultraviolet ray preventing effect. In Examples 1 to 8, no skin trouble or solid precipitation due to low-temperature storage was observed at all. In addition, as an ultraviolet absorber, 2-amino-4-methyl-6-
2-amino- in place of morpholinopyrimidine-3-oxide
4-methyl-6-thiomorpholinopyrimidine-3-oxide or 2-amino-4-methyl-6- (1-piperazinyl) pyrimidine-3
The same effect was obtained when -oxide was used.

Example 9 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 Glycerin Monooleate 2.0 POE (60 ) Hardening castor 2.0 Tocopherol acetate 0.05 Ethyl paraben 0.2 Butyl paraben 0.1 Perfume Appropriate amount (aqueous phase) 2-Amino-4-methyl-6-morpholinopyrimidine-3-oxide 1.0 2- Amino-4-methyl-6- (1-piperazinyl) pyrimidine-3-oxide 1.0 Sodium bisulfite 0.01 Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.2 Ion Exchange water residue (Preparation method) Dissolve the oil phase and the aqueous phase at 70 ° C., mix the oil phase with the aqueous phase, emulsify with an emulsifier, Cooled to ° C.

The emulsion of Example 9 also had an excellent ultraviolet ray preventing effect, and no skin troubles or solid deposition due to low-temperature storage were observed.

Example 10 Solid Powder Foundation (1) Talc 15.0 (2) Sericite 10.0 (3) Spherical Nylon Powder 10.0 (4) Porous Silicic Anhydride 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-Amino-4-methyl-6-morpholinopyrimidine-3-oxide 5.0 (10) Liquid paraffin residue (11) Glycerin triisooctanoate 15.0 (12) Sorbitan sesquioleate 1.5 (13) Preservatives qs (14) Flavor qs (production method) (1)- To the place where each component of (8) was mixed and pulverized,
A mixture of the components (9) to (14) was added, mixed with stirring, and molded into a container to obtain a solid foundation.

Example 11 Water-in-oil Emulsion Foundation (1) Spherical Nylon 10.0 (2) Porous Silicic Anhydride Powder 8.0 (3) Titanium Mica 2.0 (4) Silicone Treated Sericite 2 0.0 (5) Siliconized mica 12.0 (6) Siliconized titanium dioxide 5.0 (7) Siliconized iron oxide 2.0 (8) Ion exchange water residue (9) 2-Amino-4-methyl- 6-morpholinopyrimidine-3-oxide 5.0 (10) decamethylcyclopentanesiloxane 18.0 (11) dimethylpolysiloxane 5.0 (12) squalane 1.0 (13) polyoxyethylene-modified dimethylpolysiloxane 0 (14) Appropriate amount of preservative (15) Appropriate amount of perfume (Production method) Add and disperse (1) to (7) into a mixture obtained by uniformly mixing and dissolving the components (10) to (15). Let Was.
To this dispersion was added (8) in which (9) was dissolved, and the mixture was emulsified and filled in a container to obtain a water-in-oil emulsion foundation.

Example 12 White Powder (1) Talc Residue (2) Sericite 10.0 (3) Spherical Nylon Powder 10.0 (4) Boron Nitride 5.0 (5) Iron Oxide 3.0 (6) Carbonic Acid Magnesium 5.0 (7) Squalane 3.0 (8) Glycerin triisooctanoate 2.0 (9) Sorbitan sesquioleate 2.0 (10) 2-Amino-4-methyl-6-morpholinopyrimidine-3-oxide 3.0 (11) Appropriate amount of preservative (12) Appropriate amount of fragrance (Production method)
A mixture of each of the components (7) to (12) was added and mixed with stirring to obtain a white powder.

Example 13 Eyeshadow (1) Talc Residue (2) Mica 15.0 (3) Spherical Nylon Powder 10.0 (4) Boron Nitride 5.0 (5) Iron Oxide 3.0 (6) Oxidation Titanium-coated mica 5.0 (7) Squalane 3.0 (8) Glycerin triisooctanoate 2.0 (9) Sorbitan sesquioleate 2.0 (10) 2-Amino-4-methyl-6-morpholinopyrimidine-3 -Oxide 2.0 (11) Preservative appropriate amount (12) Flavor appropriate amount (Production method) When the components (1) to (6) are mixed and ground,
A mixture of the components (7) to (12) was added, and the mixture was stirred and mixed to obtain an eye shadow.

Example 14 Lipstick (1) Carnauba wax 0.5 (2) Candelilla wax 5.0 (3) Celesin 10.0 (4) Squalane residue (5) Glycerin triisostearate 10.0 (6) Diisostearin Glycerin acid 20.0 (7) Macadamia nut oil fatty acid cholesteryl 4.0 (8) Synthetic sodium-magnesium 0.5 (9) Hydrophobic silica 0.5 (10) 2-Amino-4-methyl-6-morpholino Pyrimidine-3-oxide 1.0 (11) Ion-exchanged water 2.0 (12) Suitable amount of colorant (13) Suitable amount of preservative (14) Suitable amount of fragrance (Production method) 8) and (9) were dispersed, and (10) and (11), which were uniformly dissolved therein, were added thereto and sufficiently stirred. Separately heated and dissolved (1) ~
This was added to (6), and the mixture was sufficiently stirred.
(14) was added, and the mixture was dispersed and stirred, and then molded to obtain a lipstick.

Each of the makeup cosmetics of Examples 10 to 14 had an excellent ultraviolet ray preventing effect, and no skin trouble, precipitation of the ultraviolet absorbent due to low-temperature storage, discoloration with time, and the like were not observed. In addition, as an ultraviolet absorber,
Instead of 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide, 2-amino-4-methyl-6-thiomorpholinopyrimidine-3-oxide, or 2-amino-4-methyl-6- (1 Similar effects were obtained when (piperazinyl) pyrimidine-3-oxide was used.

[0077]

As described above, the pyrimidine derivative of the present invention has very excellent ultraviolet absorbing ability and water solubility as a water-soluble wide-area ultraviolet absorber, and has high safety and stability. Therefore, by blending this, a skin external preparation having a high ultraviolet ray preventing effect, good stability and safety can be obtained. Further, since the pyrimidine derivative has no absorption in the visible region, there is no problem of coloring of the product.

[Brief description of the drawings]

FIG. 1 shows 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide according to one embodiment of the ultraviolet absorbent of the present invention, and a comparative compound, 2-hydroxy-4-methoxy-5-sulfo. It is a figure which shows the ultraviolet-ray absorption spectrum of sodium xonium benzophenone.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 7/42 A61K 7/42 31/00 617 31/00 617J 31/505 601 31/505 601 F term ( Reference) 4C083 AA082 AA122 AB032 AB152 AB232 AB242 AB282 AB352 AB432 AC012 AC022 AC072 AC092 AC102 AC122 AC132 AC182 AC242 AC372 AC392 AC402 AC432 AC482 AC642 AC851 AC852 AC861 AC862 AD042 AD072 AD092 AD262 AD272 AD332 AD352 CC492 CC1212 DD23 DD31 DD33 DD41 EE17 4C086 AA01 AA02 BC42 BC50 BC73 BC88 GA07 GA09 GA10 GA12 MA01 MA02 MA04 MA05 MA63 NA14 ZA89

Claims (12)

[Claims] 1. An ultraviolet absorber comprising the following pyrimidine derivative (1) or a salt thereof as a main component. Embedded image (In the general formula (1), R ¹ represents hydrogen or an alkyl group having 1 to 3 carbon atoms. A is any of the following groups (2a) to (2c).) Embedded image (In the general formula (2b), R ² is a hydrogen atom or a group having 1 to 3 carbon atoms.
Means an alkyl group. ) 2. The ultraviolet absorbent according to claim 1, wherein
An ultraviolet absorber, wherein R ¹ is a methyl group. 3. The ultraviolet absorbent according to claim 1, wherein A is the group (2a). 4. The ultraviolet absorbent according to claim 1, wherein A is the group (2b). 5. The ultraviolet absorbent according to claim 4, wherein
An ultraviolet absorber, wherein R ² is a hydrogen atom. 6. The ultraviolet absorbent according to claim 1, wherein A is the group (2c). 7. An ultraviolet absorbing composition comprising the ultraviolet absorbent according to claim 1. Description: 8. An external preparation for skin, comprising the ultraviolet absorbent according to claim 1. Description: 9. The external preparation for skin according to claim 8, further comprising an inorganic powder. 10. An external preparation for sunscreen comprising the external preparation for skin according to claim 8 or 9. 11. A sunscreen skin care cosmetic comprising the skin external preparation according to claim 8 or 9. 12. A makeup cosmetic comprising the external preparation for skin according to claim 8 or 9.