JP2780091B2 - Long wavelength UV absorber - Google Patents

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a long-wavelength ultraviolet absorber (hereinafter referred to as a UV-A absorber) 2. Description of the Related Art Ultraviolet rays cause various changes to the skin. Dermatologically, the working wavelength is divided into 400-320 nm long wavelength ultraviolet light, 320-290 nm medium wavelength ultraviolet light and 290 nm or less short wavelength ultraviolet light, and they are UV-A, UT-B and UV, respectively. Normally, most of the UV light source to which humans are exposed is sunlight, but the UV light that reaches the ground is UV-A and UV-B,
UV-C is absorbed in the ozone layer and hardly reaches the ground. Among the ultraviolet rays reaching the ground, UV-B forms erythema and blisters when the skin is irradiated with a certain amount of light or more, and also increases the melanin formation, causing changes such as pigmentation to the skin . In contrast, conventionally, UV-A
Was not expected to cause too much change in the skin. However, it has recently been clarified that the skin is also affected by UV-A irradiation by electron microscopy or histochemical techniques. In particular, unlike UV-B, the energy of UV-A reaches the dermis, causing microchronic changes in the elastic fibers in the blood vessel wall and connective tissue, and these changes are thought to lead to accelerated skin aging. Have been. Also, UV-A is known to have an action of blackening the skin immediately after irradiation (immediate blackening) and to enhance the denaturing action of UV-B on the skin. It is thought to be a factor in occurrence and hatred. It is clear from these that not only UV-B but also UV
Protecting the skin from -A is also important in preventing the promotion of aging of the skin and in preventing the occurrence of spots and freckles and hatred. [Problems to be Solved by the Invention] However, studies on the effect of UV-A on the skin have a short history, and when applied to the skin, UV-A can be effectively used.
In fact, little is known about the substance that absorbs. At present, only a few dibenzoylmethane derivatives and cinnamic acid derivatives are known as such substances, and further considering their compatibility with other components, these are not sufficiently satisfactory. (West German Patent Publication Nos. 2728241 and 2728243, JP-A-51-6164)
Nos. 1, 52-46056, 57-197209, and JP-A-57-59840). Accordingly, when these UV-A absorbers are added to and blended with cosmetics, the properties of the base of the cosmetics are restricted, and the development of more versatile UV-A absorbers has been desired. Such a UV-A absorber must satisfy the following conditions. It has a maximum absorption wavelength around 350 nm. At the above wavelength, the molar extinction coefficient (ε) is sufficiently large. Since coloring as a cosmetic composition is not desirable, absorption in the visible region is small, that is, ε ≒ 0 at 400 nm or more.
That. Be stable against heat and light. No toxicity, irritation or other adverse effects on the skin. Excellent compatibility with cosmetic base. When applied to the skin, it is not easily absorbed percutaneously and is not easily removed by perspiration. Therefore, the effect must last effectively. Inexpensive. [Means for Solving the Problems] The present inventor has conducted intensive studies in view of such circumstances, and as a result, a dibenzoylmethane derivative having a specific substituent has been obtained.
The inventors have found that all the above conditions are satisfied, and have completed the present invention. That is, the present invention provides a compound represented by the general formula (I): Wherein R ₁ and R ₂ are the same or different and have 1 to 1 carbon atoms.
Represents 24 linear or branched aliphatic hydrocarbon groups, and n
Y and m Zs are the same or different and are each 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 number 2 or 3) an oxide group, m and n
Each represents an integer of 0 to 3]. A long-wavelength ultraviolet absorber containing a dibenzoylmethane derivative represented by the following formula: The dibenzoylmethane derivative represented by the general formula (I) is substituted with a monoester (III) of a substituted phthalic acid (which may be an ortho-form, a meta-form, a para-form or any isomer) according to the following reaction formula. It is preferable to produce the compound by condensing acetophenone (III) in the presence of a far-group catalyst. (Wherein, R represents a methyl group or an ethyl group, and R ₁ , R ₂ ,
Y, Z, m and n are the same as those described above.) Also, among the compounds represented by the formula (I), When the group is substituted at the ortho position, according to the following reaction formula,
The dibenzoylmethanecarboxylic acid derivative (IV) is reacted with a halogenating reagent in a solvent inert to the reaction to form the phenacylidenephthalide derivative (V), and then the compound (V) is dissolved in a solvent inert to the reaction. To react with a secondary amine. (Wherein, R ₁ , R ₂ , Y, Z, m and n are the same as described above) Among the dibenzoylmethane derivatives thus obtained, Compounds in which the group is substituted in the ortho position are preferred and can be further subdivided into the following classes of compounds. The following general formula (VI) (Wherein R ₁ and R ₂ are the same as above). The following general formula (VII) Wherein, R ₃ is (preferably an alkyl or alkylene group of a straight-chain or branched-chain having 1 to 4 carbon atoms) hydrocarbon group having 1 to 18 hydrogen atoms or carbon atoms indicates, R _1, R ₂ is the 4'-alkoxydibenzoylmethane derivative represented by the following formula: The following general formula (VIII) (Wherein R ₁ , R ₂ , and R ₃ are the same as described above). The following general formula (IX) (Wherein R ₁ and R ₂ are the same as above, and b and c each represent an integer of 1 to 6, preferably 1 to 3) 3 ′, 4′-bis (polyoxyethyleneoxy)- Dibenzoylmethane derivative. The following general formula (X) (In the formula, R ₁ and R ₂ are the same as above. A represents an integer of 1 to 10, preferably 1 to 6.) 4'-polyoxyethyleneoxydibenzoylmethane derivative represented by the following formula: The following general formula (XI) (Wherein R ₁ , R ₂ , R ₃ and a are as defined above). 4′-Alkoxy-3′-polyoxyethyleneoxydibenzoylmethane derivative represented by the formula: The following general formula (XII) (Wherein R ₁ , R ₂ and R ₃ are the same as described above). The following general formula (XIII) (Wherein R ₁ , R ₂ and a are the same as above). 3 ′, 4′-Bis (polyoxypropyleneoxy) dibenzoylmethane derivative The following general formula (XIV) (Wherein, R ₁ , R ₂ and R ₃ are the same as above. R ₄ has 1 to 2 carbon atoms.
4, preferably 1 to 18 linear or branched alkyl or alkenyl groups) The following general formula (XV) (Wherein, R ₅ represents a linear or branched aliphatic hydrocarbon group having 1 to 24 carbon atoms, and R ₁ and R ₂ are the same as described above). Of these, 4'-alkoxydibenzoylmethane derivatives (general formula (VII)) and dialkoxydibenzoylmethane derivatives (general formula (XII) or (XIV)) are preferred. The UV-A absorber of the present invention is produced by adding a dibenzoylmethane derivative (I) to a carrier and mixing.
The carrier only needs to be inert to the dibenzoylmethane derivative (I), and may be any of a solid, liquid, emulsion, foam, gel and the like. Typical examples thereof include water, alcohols, fats (eg, hydrocarbon oils, fatty acid esters, long-chain alcohols, silicone oils), fine powders of starch or talc, low-boiling hydrocarbons used as aerosol propellants, and the like. Halogen hydrocarbon and the like. The UV-A absorber of the present invention further contains other components such as a preservative, a fragrance, a coloring agent, and a surfactant as long as the UV-A absorption of the dibenzoylmethane derivative is not impaired. be able to. Further, the dibenzoylmethane derivative (I) of the present invention
Substituent By changing the R ₁ and R ₂ of the above, it is possible to impart an affinity to the cosmetic base without impairing the UV-A absorption effect. Can be added and blended. That is, the hydrophilic / lipophilic balance (HLB balance) can be adjusted by adjusting the length of the hydrocarbon chain of R ₁ and R ₂ , and it can be used in various cosmetics in a state having an optimum affinity with the cosmetic base. Further, the HLB balance can be changed by appropriately changing Y and Z in the general formula (I). For example, water solubility can be increased by introducing a hydroxyl group or a polyethylene oxide group, and fat solubility can be increased by introducing an alkoxy group or a polypropylene oxide group. The cosmetic containing the dibenzoylmethane derivative (I) (hereinafter referred to as the present cosmetic) is a dibenzoylmethane derivative (I) having an affinity for the cosmetic base.
Is appropriately selected, and this is blended with a known cosmetic base by a conventional method, and creams, solutions, oils, sprays, stakes,
It is prepared in the form of emulsions, foundations, ointments and the like. That is, by selectively using the dibenzoylmethane derivative (I) in accordance with the cosmetic base, an oil-based cosmetic oil, an oily cream or oily emulsion containing a large amount of oil, or a weak oil containing a large amount of water Creams and weak oily emulsions,
From cosmetics such as water-based lotions to make-up cosmetics such as foundations and lipsticks based on oils, cosmetics of all forms having UV-A absorption can be produced. Suitable bases and solvents include hydrocarbons such as solid or liquid paraffin, crystal oil, ceresin, ozokerite or montan wax; vegetable oils such as olive, ground wax, carnauba wax, lanolin or whale wax or animal-based Fatty oils and waxes; fatty acids such as stearic acid, palmitic acid, oleic acid, glycerin monostearate, glycerin distearate, glycerin monooleate, isopropyl myristate, isopropyl stearate or butyl stearate, and the like; Esters: alcohols such as ethyl alcohol, isopropyl alcohol, cetyl alcohol, stearyl alcohol, palmityl alcohol and hexyl decyl alcohol; Further, polyhydric alcohols having a moisturizing action such as glycol, glycerin or sorbitol can also be used. The blending amount of the dibenzoylmethane derivative in the cosmetic of the present invention is not particularly limited because it can vary depending on the use form, and may be present in an effective amount, but generally 0.1 to 20% by weight, preferably 0.5 to 20% by weight in the composition. It is good to mix so that it may be ~ 10% by weight. The cosmetic of the present invention may contain only a dibenzoylmethane derivative, but is more preferably used as a normal sunscreen cosmetic in combination with another UV-B absorber. As such a UV-B absorber, for example, p-
Methylbenzylidene-D, L-camphor or sodium sulfonic acid salt; 2-phenylbenzimidazole-
5-sulfonic acid sodium salt, 3,4-dimethylphenylglyoxylic acid sodium salt, 4-phenylbenzophenone, 4-phenylbenzophenone-2'-carboxylic acid isooctyl ester, p-methoxycinnamic acid ester ,
2-phenyl-5-methylbenzoxazole or p-
And dimethylaminobenzoic acid esters. In addition to the above components, various additives can be added to the cosmetic of the present invention. Suitable additives include, for example, W /
O-type and O / W-type emulsifiers are included. As the emulsifier, a commercially available emulsifier can be used. Thickeners such as methylcellulose, ethylcellulose or carboxymethylcellulose, polyacrylic acid, tragacanth, agar or gelatin can also be added as additives. Furthermore,
If necessary, flavors, preservatives, humectants, emulsion stabilizers, medicinal ingredients and / or physiologically acceptable coloring agents may be added. [Functions and Effects of the Invention] The dibenzoylmethane derivatives used in the present invention are odorless, slightly yellow crystals or oily substances, and effectively absorb ultraviolet rays in the UV-A region causing harmful effects as described above. Protects the skin from the adverse effects of this. It is stable to light and heat over time, hardly hydrolyzes in cosmetics, and has excellent solubility in solvents commonly used for cosmetics. It is extremely useful as a UV absorber for foods. [Examples] Next, reference examples and examples will be described. Reference Example (i) Synthesis of 3- (4'-methoxyphenacylidene) phthalide: 4'-methoxy-2-carboxydibenzoylmethane (100 g, 0.34 mol) was added to methylene chloride (400 ml), and this suspension was added. Then, thionyl chloride (60.94 g, 0.51 ml) is added at once, and the mixture is stirred at 30 ° C. for 1 hour and further at reflux temperature for 3 hours to complete the reaction. When the solvent and excess thionyl chloride are distilled off under reduced pressure, the desired 3- (4'-methoxyphenacylidene) phthalide (mixture of Z-form and E-form) is almost quantitatively obtained from the reaction mixture solution. The ratio between the Z-isomer and the E-isomer was 30:70 as determined from the integral ratio of olefin hydrogen in NMR, and the E-isomer produced more. Both Z-form and E-form are in the next stage (ii)
Can be used for the reaction of By washing the mixture with hot acetone, almost pure E-form can be separated as yellow needles (yield: about 65%). mp 163-164 ° C IR ν _max (KBr) cm ^-1 : 1975,1660,1605,1510,1470,1420,1395,1310,1255,1180,1065,975 A compound dissolved in heated acetone is applied to a silica gel column. After purification by chromatography, pure Z form was obtained as yellow needles. mp 172 to 173 ° C IR ν _max (KBr) cm ^-1 1795,1670,1615,1590,1510,1470,1365,1330,1300,1260,1220,1165,1080,1005,965 (ii) 4'-methoxy Synthesis of 2- (N, N-diethylcarbamoyl) dibenzoylmethane: 3- (4'-methoxyphenacylidene) phthalide (10 g, 35.7 mmol) and diethylamine (10.3 g, 140.8 mmol) were added to toluene (60 ml). In addition, stirring is continued for 6 hours while heating under reflux. The reaction mixture is cooled to room temperature, diluted with ether, and washed twice with a 12% aqueous hydrochloric acid solution, then once with a saturated aqueous sodium hydrogen carbonate solution and once with a saturated saline solution. After drying using sodium sulfate, the solvent is distilled off under reduced pressure to obtain a brown oil. This was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 20).
0/1 to 3/1) and purified as a pale yellow solid.
The desired 4'-methoxy-2- (N, N-diethylcarbamoyl) dibenzoylmethane (9.69 g) was obtained (yield: 77).
%). _{mp 77~78.8 ℃ NMR (CDCl 3)} δppm: 0.97 (3H, t, J = 7Hz, -CH 3) 1.14 (3H, t, J = 7Hz, -CH 3) 2.86~3.73 (4H, m, -CH ₂ CH ₃ × 2) 3.80 (3H, s, -OCH ₃ ) 6.67 (1H, s, olefin hydrogen) 6.76 to 7.10 (2H, m, benzene hydrogen) 7.14 to 8.10 (6H, m, benzene hydrogen) 16.58 (1H, bs, enol _{hydrogen) IR ν max (KBr) cm} -1: 2970,2950,2890,1730,1600,1510, 1465,1290,1260,1230,1175,1115, 1090,1060,1035 UV λ max (EtOH) nm: 353 nm, log ε λ _max = 4.38 Example 1 A cream having the following composition containing the dibenzoylmethane derivative (I) according to the present invention was prepared by a conventional method, and this cream was UV-A The effect of protecting the skin from irradiation was examined by the following test method. The results are shown in FIG. [Composition] Dibenzoylmethane derivative (I) ^* 2.0 (% by weight) Polyoxyethylene (20) 2.0 Sorbitan monooleate Sorbitan monooleate 2.0 Isopropyl myristate 18.0 Squalane 7.0 2-Ethylhexanoic acid triglyceride 12.0 Antioxidant Appropriate amount Purification Water 51.0 Propylene glycol 5.0 Preservatives Appropriate amount Fragrance 〃 * Product 1 of the present invention 4'-methoxy-2- (N, N-diethylcarbamoyl) dibenzoylmethane Product 2 of the present invention 3 ', 4'-dimethoxy-2- ( N, N-Dibutylcarbamoyl) dibenzoylmethane Product of the present invention 34'-Ethoxy-2- (N, N-dimethylcarbamoyl) dibenzoylmethane [Test method] Method such as Gschnait [Archive
Archives of Derm
atological Research) 263 , 181-188 (1978)]. That is, the back hair of the guinea pig was first shaved to expose the skin, and the sensitivity to UV-A was increased by intraperitoneal administration of 8-methoxypsoralen in advance. Next, the products 1 to 3 of the present invention previously shown on the back shaved skin
Was applied in an amount of ² mg / cm ² , and 15 minutes later, UV-A irradiation was performed. At 24 hours after the irradiation, the appearance of erythema on the skin was observed, and the minimum UV-A irradiation time for producing erythema on the skin was determined. This time is compared with the minimum UV-A irradiation time that causes erythema on the unapplied skin, and the sun protection factor (hereinafter abbreviated as SPF) is calculated from the following equation.
And the skin protective effect of each compound was examined. In addition, as a comparative product, a cream base only (comparative product 1) in which the dibenzoylmethane derivative was replaced with water in the above composition (comparative product 1) and petrolatum (comparative product 2) were used. From the results of this test, the cream base alone and vaseline application cannot protect the ultraviolet rays, but the cream containing 2% of the dibenzoylmethane derivative according to the present invention shows an SPF value of around 6 to 8, It can be seen that UV-A rays are effectively protected. Example 2 Lotion: The following composition was blended according to a conventional method to prepare a lotion. [Composition] 4'-methoxy-2- (N, N-diethylcarbamoyl) dibenzoylmethane 2.0 (% by weight) Glycerin 2.0 Propylene glycol 5.0 Ethanol 10.0 Polyoxyethylene (20) 1.0 Hexadecyl ether Purified water 79.0 Preservative Appropriate amount Fragrance 〃 Chromium fine amount Example 3 Emulsion: An emulsion was prepared by blending the following compositions according to a conventional method. [Composition] 3 ', 4'-Dimethoxy-2- (N, N-dibutylcarbamoyl) dibenzoylmethane 5.0 (% by weight) Stearic acid 1.5 Cetanol 1.0 Oleic acid monoglyceride 0.5 Vaseline 2.0 Liquid paraffin 6.0 Squalane 6.0 Purified water 69.0 Triethanol Amine 0.8 Dipropylene glycol 5.0 Glycerin 2.0 Carboxyvinyl polymer 0.2 Preservative Appropriate amount Fragrance 実 施 Example 4 Emulsion: The following composition was blended according to a conventional method to prepare an emulsion. [Composition] 4'-ethoxy-2- (N, N-dimethylcarbamoyl) dibenzoylmethane 1.5 (wt%) stearyl alcohol 0.5 stearic acid 2.4 cetanol 1.0 isopropyl myristate 10.0 liquid paraffin 5.0 petrolatum 2.0 purified water 71.0 triethanolamine 1.0 Glycerin 5.0 Preservative Appropriate amount Fragrance 〃 Example 5 Oily foundation: The following composition was blended according to a conventional method to prepare an oily foundation. [Composition] 2 ', 4'-Dimethoxy-2- (N, N-dihexylcarbamoyl) dibenzoylmethane 5.0 (% by weight) 2-ethylhexyl p-methoxycinnamate 5.0
Liquid paraffin 15.0 Isopropyl palmitate 16.0 Lanolin alcohol 3.0 Microcrystalline wax 7.0 Ozokerite 8.0 Candeira wax 0.5 Preservatives Appropriate amount Antioxidant 〃 Flavor チ タ ン Titanium oxide 15.0 Kaolin 15.0 Talc 6.0 Bengala 1.5 Yellow iron oxide 2.0 Black iron oxide 0.5 Example 6 Lipstick: The following composition was blended according to a conventional method to prepare a lipstick. [Composition] 4'-methoxy-2- (N, N-dimethylcarbamoyl) dibenzoylmethane 2.0 (% by weight) p-dimethylaminobenzoic acid 2.0 Castor oil 40.3 Hexadecyl alcohol 25.0 Lanolin 4.0 Beeswax 5.0 Candelilla wax 7.0 Carnauba wax 6.0 Antioxidation Preservative チ タ ン Titanium oxide 2.0 Red 202 No. 0.5 〃 204 No. 2.5 〃 227 Al Lake 2.5 Orange No. 201 0.2 Perfume

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing SPF values of inventive products 1 to 3 and comparative products 1 and 2.

────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Genji Imokawa 1022-89, Himurocho, Utsunomiya City (72) Inventor Naotake Takaishi 1022-24, Himurocho, Utsunomiya City (58) Fields surveyed (Int.Cl. ⁶ , DB Name) C09K 3/00 A61K 7/44 CA (STN)

Claims (1)

(57) [Claims] General formula (I) Wherein R ₁ and R ₂ are the same or different and have 1 to 1 carbon atoms.
Represents 24 linear or branched aliphatic hydrocarbon groups, and n
Y and m Zs are the same or different and are each 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 number 2 or 3) an oxide group, m and n
Each represents an integer of 0 to 3]. A long-wavelength ultraviolet absorber containing a dibenzoylmethane derivative represented by the following formula: 2. The long-wavelength ultraviolet absorber according to claim 1, which is a cosmetic.