JPS6410491B2 - - Google Patents

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a long-wavelength ultraviolet absorber, and more specifically, a long-wavelength ultraviolet absorber containing a dibenzoylmethane derivative polyvalent metal salt, and the long-wavelength ultraviolet absorber. Concerning cosmetics containing the following. [Prior Art] It is known that ultraviolet rays cause various changes in the skin. Dermatologically, the wavelength of action is
UV-A, UV-B, and UV-C are divided into long-wavelength ultraviolet rays from 400 to 320 nm, medium-wavelength ultraviolet rays from 320 to 290 nm, and short-wavelength ultraviolet rays below 290 nm, respectively.
It is called. Normally, most of the sources of ultraviolet radiation to which humans are exposed are sunlight, but the ultraviolet rays that reach the ground are UV-A and UV-B, while UV-C is absorbed in the ozone layer and almost never reaches the ground. Among the ultraviolet rays that reach the ground, UV-B forms erythema and water spots when the skin is irradiated with more than a certain amount of light.
In addition, melanin formation is enhanced, causing changes in the skin such as pigmentation. On the other hand, conventionally,
It was thought that UV-A did not cause much change in the skin. However, it has recently been revealed through electron microscopy and histochemical techniques that the skin undergoes changes even when exposed to UV-A irradiation. In particular, unlike UV-B, UV-A's energy reaches the dermis, causing micro-chronic changes in the elastic fibers in blood vessel walls and connective tissues, and these changes are thought to lead to accelerated skin aging. It is being In addition, UV-A has the effect of blackening the skin immediately after irradiation (immediate blackening), and UV-B
It is known that UV-A enhances the degenerative effect on the skin, and UV-A is thought to be a factor in the occurrence and aggravation of age spots and freckles. As is clear from these facts, it is important to protect the skin not only from UV-B but also from UV-A in order to prevent accelerated aging of the skin and to prevent the occurrence and aggravation of age spots and freckles. However, research on the effects of UV-A on the skin has a short history, and when applied to the skin,
The reality is that not much is known about substances that effectively absorb UV-A. A few dibenzoylmethane derivatives and cinnamic acid derivatives have been known in the past, but most of them are fat-soluble (West German Patent Publication No. 2728241, West German Patent Publication No. 2728243, Japanese Patent Application Laid-Open No. 1983-61641). Publication No. 52-46056, No. 57
-107209), and there were few water-soluble ones (Japanese Patent Application Laid-Open No. 57-29840). The present inventors have found that the material is water-soluble and meets the following requirements for a long-wavelength ultraviolet absorber: It has a maximum absorption wavelength around 350 nm. The molar extinction coefficient (ε) is sufficiently large at the above wavelength. Since coloring is undesirable in cosmetic compositions, the absorption in the visible region is low, i.e.
ε≒0 at 400 nm or more. Must be stable against heat and light. No toxicity, irritation, or other harmful effects on the skin. Excellent compatibility with cosmetic bases. When applied to the skin, it is difficult to absorb through the skin,
Difficult to remove due to sweating, etc. Therefore, the effect must be effectively connected. It must be cheap. As a compound that satisfies the following formula (), [wherein, n Y's and m Z's are each the same or different and each represents a hydroxyl group, a linear or branched aliphatic hydrocarbon group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, or a polyoxyalkylene (carbon We discovered a dibenzoylmethane derivative represented by the formula (2 or 3) oxide group, and m and n each represent an integer of 0 to 3, and filed a patent application (Japanese Patent Laid-Open No. 190708/1983). [Problem to be solved by the invention] However, including the compound of the above formula (),
Conventional UV absorbers include water, organic solvents, oily substances,
Because it dissolves in sebum, etc., is absorbed transdermally, and diffuses on the skin, it poses problems in terms of safety for the human body and sustainability of its effects. Therefore, it has been desired to provide a compound that is insoluble in water, organic solvents, oily substances, sebum, etc., and that efficiently absorbs UV-A. [Means for solving the problem] The present inventors have solved the above-mentioned compound of formula ().
As a result of various studies, it was discovered that by converting the compound into a polyvalent metal salt, it becomes insoluble in water, organic solvents, etc. without affecting UV-A absorption, and the present invention was completed. Therefore, the present invention provides the following formula (), [In the formula, M is an aluminum atom, a zinc atom, a calcium atom, a magnesium atom, a barium atom,
Strontium atom or zirconium atom, m
represents the valence of M, n Y's and l Z's are each the same or different, a hydroxyl group, a carbon number of 1 to 24
represents a linear or branched aliphatic hydrocarbon group, an alkoxy group having 1 to 24 carbon atoms, or a polyoxyalkylene (2 or 3 carbon atoms) oxide group, and l and n each represent an integer of 0 to 3.] The present invention provides a long-wavelength ultraviolet absorber containing a polyvalent metal salt of a dibenzoylmethane derivative represented by the following formula, and a cosmetic containing the long-wavelength ultraviolet absorber. Japanese Patent Application No. 60-57026 and U.S. Patent No. 4,381,360 have conventionally used dibenzoylmethanes after making them insolubilized. It is a composite with a hydrous oxide, and is also known as
No. 4381360 is a stabilizer against heat and light for polyvinyl halide resin, which is made of dibenzoylmethane as an enolate salt with a metal ion, and is a stabilizer for polyvinyl halide resin against heat and light. This is different from a wavelength ultraviolet absorber. The dibenzoylmethane derivative polyvalent metal salt () used in the present invention can be prepared by adding a water-soluble polyvalent metal salt () to the dibenzoylmethane derivative (') according to the following formula, for example.
It is prepared by reacting with an aqueous solution of (In the formula, X' represents a hydrogen atom, a monovalent metal cation, or an organic cation, and L represents a halogen atom, nitrate, sulfate, or alkyl carboxylate. M, Y, Z, l, m, and n have the meanings described above. All of the dibenzoylmethane derivatives represented by formula (') are water-soluble, and the compounds can be prepared by known methods such as Ann. Chim. (Rone), 48 , 762.
(1958), J.Chem.Soc., 2063 (1952), Pestic.
4, 473 (1973) and US Pat. No. 4,381,360. The easiest manufacturing method is according to the reaction formula below,
Substituted acetophenone () is condensed with monoester () of substituted phthalic acid (ortho, meta, para, or any isomer) in the presence of a base catalyst to obtain compound (a), and then further processed by a conventional method. This method is used to obtain the desired salt. (In the formula, R represents a methyl group or an ethyl group, Y,
(Z, m and n are the same as above) In addition, when phthalic acid is ortho form, the following general formula () is used instead of the above monoester (), (In the formula, Z and m are the same as above.) An acid anhydride represented by the following can also be used. The dibenzoylmethane derivative represented by the general formula (a) can be further subdivided into the following compound groups. The following general formula (), (In the formula, X' represents a hydrogen atom, a monovalent metal cation, or an organic cation, and the substitution position of -COOX' represents the ortho, meta, or para position.) Dibenzoylmethanecarboxylic acid (salt) represented by: The following general formula (), [In the formula, R ₁ represents a hydrogen atom or a hydrocarbon group having 1 to 18 carbon atoms (preferably a linear or branched alkyl group or alkylene group having 1 to 4 carbon atoms), and the substitution position of -COOX' and X' is the same as above] 4'-Alkoxydibenzoylmethanecarboxylic acid (salt) represented by: The following general formula (), 3'-hydroxy-4'-alkoxydibenzoylmethanecarboxylic acid (salt) represented by the formula (in the formula, the substitution position of -COOX', X' and _R1 are the same as above). The following general formula (), 2,3'-dihydroxy-4'-alkoxydibenzoylmethanecarboxylic acid (salt) represented by the formula (in the formula, the substitution position of -COOX', X' and _R1 are the same as above). The following general formula (XI), (In the formula, the substitution position of -COOX', X' and R ₁ are the same as above. a represents an integer of 1 to 10, preferably 1 to 6) Oxydibenzoylmethanecarboxylic acid (salt). The following general formula (XII), (In the formula, the substitution position of -COOX' and X' are the same as above. b and c each represent an integer of 1 to 6, preferably 1 to 3.) Ethyleneoxy)-dibenzoylmethanecarboxylic acid (salt). The following general formula (), (In the formula, the substitution position of -COOX', X' and a are the same as above.) 4'-Polyoxyethyleneoxydibenzoylmethanecarboxylic acid (salt). The following general formula (), (In the formula, the substitution position of -COOX', X', R ₁ and a
is the same as above) 4'-alkoxy-3'-polyoxyethyleneoxydibenzoylmethanecarboxylic acid (salt) represented by: Among these compounds ('), more preferable examples include dibenzoylmethane-2-
Carboxylic acid triethanolamine salt, sodium dibenzoylmethane-3-carboxylate, sodium 4'-methoxybenzoylmethane-2-carboxylate, sodium 4'-methoxydibenzoylmethane-3-carboxylate, 3'-hydroxy-4 '-Methoxydibenzoylmethane-2-carboxylic acid, 2,
Sodium 3'-dihydroxy-4'-methoxybenzoylmethane-5-carboxylate, 4'-methoxy-
Potassium 2-polyoxyethyleneoxydibenzoylmethane-5-carboxylate, sodium 3',4'-bis(polyoxyethyleneoxy)-dibenzoylmethane-3-carboxylate, 4'-methoxydibenzoylmethane-4- Potassium carboxylate, 4′-
Polyoxyethyleneoxydibenzoylmethane
Sodium 4-carboxylate, 4'-methoxy-3'-
Examples include potassium polyoxyethylenedibenzoylmethane-4-carboxylate, among which, especially
Monovalent metal and organic salts of 4'-methoxydibenzoylmethane-2-carboxylic acid are preferred. In addition, water-soluble polyvalent metal salts of formula () include, for example, aluminum chloride, calcium acetate, magnesium sulfate, zinc nitrate, barium chloride, zirconium sulfate, strontium chloride, magnesium chloride, zinc acetate, aluminum nitrate, aluminum sulfate,
Examples include zinc nitrate, calcium sulfate, barium sulfate, and strontium sulfate. The polyvalent metal salt () aqueous solution is added gradually while stirring the system. In the reaction, it is preferable to use an alkaline aqueous solution and add the polyvalent metal salt () aqueous solution while adjusting the pH of the system to 8.0 to 9.0. By doing so, the compound of the present invention ()
can be obtained as a precipitate. In the reaction, the polyvalent metal salt () reacts with the compound (),
It is preferable to add it in an amount of 1.2 to 3 equivalents. The ultraviolet absorber of the present invention is a dibenzoylmethane derivative polyvalent metal salt () obtained as described above.
It is manufactured by adding and mixing with a carrier.
The carrier may be inert to the dibenzoylmethane derivative polyvalent metal salt (), and may be solid,
It may be a liquid, emulsion, foam, gel, etc. Typical examples include water, alcohol, fats and oils (e.g. hydrocarbon oils, fatty acid esters, long chain alcohols, silicone oils), fine powders of starch or talc, low-boiling hydrocarbons used as aerosol propellants, Examples include halogenated hydrocarbons. The long wavelength ultraviolet absorber of the present invention further includes UV-A of dibenzoylmethane derivatives.
Other ingredients such as preservatives, fragrances, colorants, surfactants, etc. may be added as long as they do not impair the absorption effect. The long wavelength ultraviolet absorber of the present invention can be used in various applications requiring absorption of ultraviolet rays, but
In particular, it can be suitably added to cosmetics, medical agents, and the like. The amount of the ultraviolet absorber of the present invention in these cosmetics and medical agents varies depending on the use and dosage form, etc.
For example, in the case of cosmetics, the content of dibenzoylmethane derivatives () is generally 0.1
It may be blended in an amount of up to 20% by weight, preferably 0.5 to 10% by weight. When preparing cosmetics, a long-wavelength ultraviolet absorber that has an affinity for cosmetic bases is appropriately selected, and this is blended with a known cosmetic base using a conventional method to form creams, solutions, and oils. , sprays, sticks, emulsions, foundations, ointments, etc. In other words, by selectively using long-wavelength UV absorbers in accordance with the cosmetic base, oil-based cosmetic oils, oil-based creams and emulsions that contain large amounts of oil, and weakly oil-based creams and emulsions that contain large amounts of water can be produced. From basic cosmetics such as weak oil-based emulsions and water-based lotions to make-up cosmetics such as oil-based foundations and lipsticks, SV
- It is possible to produce cosmetics in all forms that have an A-absorbing effect. Suitable bases and solvents include solid or liquid paraffin, crystal oil, hydrocarbons such as ceresin, ozokerite or montan wax; olive, earth wax,
Vegetable oils or animal fats or waxes such as carnauba wax, lanolin or spermaceti; also stearic acid, palmitic acid, oleic acid, glycerin monostearate, glycerin distearate, glycerin monooleate, isopropyl myristate, isopropyl Fatty acids and their esters such as stearate or butyl stearate;
Examples include alcohols such as ethyl alcohol, isopropyl alcohol, cetyl alcohol, stearyl alcohol, palmityl alcohol, and hexyldodecyl alcohol. Further, polyhydric alcohols having a moisturizing effect such as glycol, glycerin or sorbitol can also be used. The cosmetics of the present invention are sufficiently effective just by blending a UV absorber containing a dibenzoylmethane derivative polyvalent metal salt () as an active ingredient, but if desired, a known UV-B absorber may be further blended in combination. You can also do it. Such UV-B absorbers include, for example, p-methylbenzylidene-D, L-sulfonate or its sulfonic acid sodium salt;
Phenylbenzimidazole-5-sulfonic acid sodium salt, 3,4-dimethylphenylglyoxylic acid sodium salt, 4-phenylbenzophenone, 4-phenylbenzophenone-2'-carboxylic acid isooctyl ester, p Examples include -methoxycinnamic acid ester, 2-phenyl-5-methylbenzoxazole, and p-dimethylaminobenzoic acid ester. In addition to the above-mentioned components, various additives can be added to the cosmetic composition of the present invention. Suitable additives include, for example, W/O and O/W emulsifiers. As the emulsifier, commercially available emulsifiers can be used. Thickeners such as methylcellulose, ethylcellulose or carboxymethylcellulose, polyacrylic acid, tragacanth, agar or gelatin can also be added as additives. Furthermore, fragrances, preservatives, humectants, emulsion stabilizers, medicinal ingredients, and/or physiologically acceptable colorants may be added as necessary. [Action and Effect of the Invention] As described above, the long wavelength ultraviolet absorber of the present invention has the following properties:
It effectively blocks harmful UV-A rays, protects the skin layer, and is stable against light and heat over time. Also, water, organic solvents, oily substances,
Because it does not dissolve in sebum, etc., it is difficult to be absorbed through the skin, and water,
Since it is difficult to be removed by sweat, etc., its effects are long-lasting. Therefore, the ultraviolet absorber of the present invention is useful as an ultraviolet inhibitor, a cosmetic base, etc. in the fields of cosmetics and pharmaceuticals. [Example] Next, the present invention will be explained in detail with reference to Examples and Test Examples. Example 1 Synthesis of magnesium 4'-methoxydibenzoylmethane-2-carboxylate: 6 g of 4'-methoxydibenzoylmethane-2-carboxylic acid and 100 g of water with sodium hydroxide (95%)
dissolve in The pH at this time is 8.0. To this, gradually add an aqueous solution of 3.4 g of magnesium chloride dissolved in 50 g of water. However, at this time, adjust the pH of the reaction system by adding 1N sodium hydroxide little by little so that the pH of the reaction system does not fall below 8. Separate the precipitate after adding aqueous magnesium chloride solution,
The mixture was washed with a 0.01N aqueous sodium hydroxide solution, water, and methanol in this order to obtain 5.1 g of the title compound as a white powder. Example 2 Synthesis of zinc 4'-methoxydibenzoylmethane-2-carboxylate: Proceed as in Example 1 except that 7.0 g of zinc acetate dihydrate was used instead of magnesium chloride in Example 1. , pale yellow powder of the title compound
6.04g was obtained. Example 3 Synthesis of aluminum 4'-methoxydibenzoylmethane-2-carboxylate The following procedure was carried out in the same manner as in Example 1, except that 11.0 g of aluminum nitrate nonahydrate was used instead of magnesium chloride in Example 1. 3.73 g of pale yellow powder of the compound was obtained. Example 4 Synthesis of calcium 4'-methoxydibenzoylmethane-2-carboxylate: Except for using 5.3 g of calcium acetate monohydrate in place of magnesium chloride in Example 1,
Yellowish white powder of the title compound was prepared in the same manner as in Example 1.
6.18g was obtained. Example 5 Synthesis of barium 4'-methoxydibenzoylmethane-2-carboxylate: The same procedure as in Example 1 was carried out except that 7.3 g of barium chloride dihydrate was used in place of magnesium chloride in Example 1. Yellow-white powder of compound 7.37
I got g. Example 6 Synthesis of zirconium 4'-methoxydibenzoylmethane-2-carboxylate: Same procedure as in Example 1 except that 5.0 g of zirconium sulfate tetrahydrate was used instead of magnesium chloride in Example 1. 5.1 g of a pale yellow powder of the title compound was obtained. Test Example 1 5 mg of the various metal salts shown in Table 1 were weighed out, and after ultrasonication in 50 ml of hexane for 5 minutes, the absorbance was measured using a Shimadzu MPS-2000 self-recording spectrophotometer using a 10 mm quartz cell. The results are shown in Table 1. [Table] Example 7 Suspension type lotion: (Composition) (%) Ethanol 10 Glycerin 4 Strontium 4'-methoxydibenzoylmethane-2-carboxylate 5.5 Camphor 0.15 Fragrance Trace amount Purified water Remaining amount (manufacturing method) Ingredients Add the mixed suspension to the dissolved ingredients and stir well to obtain a product. Example 8 W/O cream: (Composition) (%) Dibenzoylmethane derivative polyvalent metal salt of Example 1 8 Vaseline 6 Cholesterol 0.6 Cetol 0.5 Sorbitan sesquiolate 2 Liquid lanolin 4 Isopropyl palmitate 8 Squalane 10 Solid paraffin 4 Glycerin 3 Preservative Appropriate amount Fragrance Trace amount Purified water Remaining amount (manufacturing method) Stir and mix the ingredients ~ at 80℃. Other ingredients are mixed, heated and dissolved at 80°C, and added to the oil phase to pre-emulsify. After uniformly emulsifying with a homomixer, the product is obtained by cooling to 30°C. Example 9 O/W type cream: (Composition) (%) Beeswax 5.5 Setanol 4.5 Hydrogenated lanolin 7 Squalane 33 Fatty acid glycerin 3.5 Lipophilic glycerin monostearate 2 Polyoxyethylene sorbitan monolaurate (20E.O.) 2 Polyvalent metal salt of dibenzoylmethane derivative of Example 2 8 Fragrance Trace amount Preservative Appropriate amount Antioxidant Appropriate amount Propylene glycol 4.5 Purified water Appropriate amount (Production method) Mix the ingredients with stirring and keep at 80°C. Mix other ingredients and heat to dissolve at 80°C. The aforementioned aqueous phase is added to this oil phase to pre-emulsify it, homogeneously emulsified using a homomixer, and then cooled to 30°C to obtain a product. Example 10 Foundation status: (Composition) (%) Dibenzoylmethane derivative polyvalent metal salt of Example 3 10 Titanium chloride (hydrophobized) 10 Kaolin 15 Talc 10 Liquid paraffin 18 Liquid lanolin 4.5 Isopropyl myristate 15 Micro Crystalline wax 4.5 Ceresin 10 Carnauba wax 2 Sorbitan sesquiolate 1 (Manufacturing method) After heating, stirring and mixing the ingredients at 80°C, pour this into a mold, cool and mold to obtain a product. Example 11 Powder foundation: (Composition) (%) Mica Remaining amount Dibenzoylmethane derivative polyvalent metal salt of Example 4 10 Talc 20 Titanium oxide 10 Red iron oxide 0.8 Yellow iron oxide 2.5 Black iron oxide 0.1 Liquid paraffin 8 Beeswax 2 Preservative: Appropriate amount Flavor: Trace amount (manufacturing method) Mix and grind the ingredients. Transfer this to a high-speed blender, add the ingredients mixed and dissolved at 80°C, and mix uniformly. After adding the ingredients to this mixture and mixing, it is ground again and passed through a sieve. This is compression molded into a metal plate. Example 12 Cream foundation: (Composition) (%) Stearic acid 5 Hydrophilic glyceryl monostearate 2.5 Cetostearyl alcohol 1 Propyl glycol monolaurate 3 Squalane 7 Olive oil 8 Purified water Remaining amount Preservative appropriate amount Triethanolamine 1.2 Sorbit 3 Titanium oxide 10 Talc 5 Color pigment Appropriate amount Dibenzoylmethane derivative polyvalent metal salt of Example 5 8 Perfume Trace amount (manufacturing method) Components ~ are mixed and pulverized. Separately, prepare a solution by mixing the aqueous phase components ~, add and disperse the pulverized pigment, and then heat to 75°C. The oil phase components ~ are heated and dissolved at 80°C and added to the previously prepared aqueous phase with stirring to emulsify. Cool this while stirring, add the ingredients at 50°C, and cool while stirring.

Claims (1)

[Claims] 1st-order equation () (In the formula, M is an aluminum atom, a zinc atom, a calcium atom, a magnesium atom, a barium atom,
Strontium atom or zirconium atom, m
represents the valence of M, and n Y and l Z are each the same or different, and represent a hydroxyl group, a carbon number of 1 to 24
represents a linear or branched aliphatic hydrocarbon group, an alkoxy group having 1 to 24 carbon atoms, or a polyoxyalkylene (2 or 3 carbon atoms) oxide group, l and n each represent an integer of 0 to 3) A long wavelength ultraviolet absorber containing a dibenzoylmethane derivative polyvalent metal salt represented by: 2nd order formula () (In the formula, M is an aluminum atom, a zinc atom, a calcium atom, a magnesium atom, a barium atom,
Strontium atom or zirconium atom, m
represents the valence of M, and n Y and l Z are each the same or different, and represent a hydroxyl group, a carbon number of 1 to 24
represents a linear or branched aliphatic hydrocarbon group, an alkoxy group having 1 to 24 carbon atoms, or a polyoxyalkylene (2 or 3 carbon atoms) oxide group, where l and n each represent an integer of 0 to 3) A cosmetic containing a long wavelength ultraviolet absorber containing a polyvalent metal salt of a dibenzoylmethane derivative represented by: