WO2008041525A1 - Composé de furylméthylènemalonamide et sel de celui-ci, absorbeur des rayons ultraviolets et préparation externe pour la peau - Google Patents

Composé de furylméthylènemalonamide et sel de celui-ci, absorbeur des rayons ultraviolets et préparation externe pour la peau Download PDF

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Publication number
WO2008041525A1
WO2008041525A1 PCT/JP2007/068434 JP2007068434W WO2008041525A1 WO 2008041525 A1 WO2008041525 A1 WO 2008041525A1 JP 2007068434 W JP2007068434 W JP 2007068434W WO 2008041525 A1 WO2008041525 A1 WO 2008041525A1
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Prior art keywords
compound
phase
malonamide
bis
salt
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PCT/JP2007/068434
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English (en)
Japanese (ja)
Inventor
Takuya Hiruma
Masaru Suetsugu
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Shiseido Company Ltd.
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Publication of WO2008041525A1 publication Critical patent/WO2008041525A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • the present invention relates to a furylmethylenemalonamide compound and a salt thereof, in particular, an ultraviolet absorber comprising the compound, an ultraviolet absorbing composition containing this as an active ingredient, and a skin external preparation containing the same.
  • 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.
  • medium-wavelength ultraviolet rays of 290 nm to 320 nm cause erythema and blister formation, increased melanogenesis, and pigmentation.
  • 320-400 nm long-wavelength ultraviolet rays have an immediate blackening effect that darkens the skin immediately after irradiation, and because the energy reaches the dermis, it also affects elastic fibers in the blood vessel wall and connective tissue. It is said to have an effect.
  • These medium to long wavelength ultraviolet rays promote skin aging and are thought to contribute to the formation of spots, freckles, wrinkles and the like.
  • ultraviolet absorbers such as benzotriazole derivatives, benzophenone derivatives, salicylic acid derivatives, paraaminobenzoic acid derivatives, cinnamic acid derivatives, urocanic acid derivatives and the like have been conventionally used. .
  • 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 ski resorts, but also in everyday life, and even 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 added to a sufficient amount of water-based skin care cosmetics such as lotion. [0006] So far, few water-soluble UV absorbers are currently used, and 2-hydroxy-4-methoxy-5-sulfononium benzophenone sodium is known.
  • the substance is a sulfonate, it has an effect on the pH of the blending system, and the ultraviolet absorption region varies depending on the pH of the blending system.
  • 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.
  • the substance has absorption even in the visible light region, it has a disadvantage that it is colored pale yellow and affects the color tone of the product.
  • 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.
  • solubility of these substances in water is low and not fully satisfactory.
  • ultraviolet absorbers are also used in fields other than pharmaceuticals and cosmetics. For example, they are added to various materials such as paints, dyes, pigments, various resins, synthetic rubbers, latexes, films and fibers. Used to maintain the quality by imparting UV-absorbing ability, protecting the product itself, or the product covered with its coating film or film from UV rays, preventing deterioration and alteration due to UV rays, etc. Yes.
  • conventional UV absorbers have the problem that they sublimate and volatilize by heating during baking of the coating film or resin molding, or gradually evaporate over time without heating. It was.
  • Patent Document 1 JP-A-10-120698
  • Patent Document 2 JP 2002-363195 A
  • the present invention has been made in view of the above-mentioned circumstances, and its problem is that it has a high water-solubility, a wide range, and an excellent ultraviolet-absorbing ability over the ultraviolet wavelength region, and its absorption in the visible region.
  • a compound having excellent yield and stability, an ultraviolet absorber comprising the compound, and having the compound An object of the present invention is to provide an ultraviolet-absorbing composition containing as an active ingredient and a skin external preparation containing the compound.
  • the first subject of the present invention is to provide a furylmethylenemalonamide compound represented by the following general formula (1) and a salt thereof.
  • R, R and R are each independently a hydrogen atom or carbon number;! To 4 linear or branched
  • R and R each represent ⁇ (CH 2) - ⁇ -R, and R represents a hydrogen atom or
  • a linear or branched alkyl group having 1 to 4 carbon atoms represents an alkyl group.
  • m is an integer from 2 to 4, n is from! to 5.
  • R and R 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 general formula (1) and / or a salt thereof.
  • the 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.
  • the skin external preparation further contains an inorganic powder.
  • the furylmethylenemalonamide compound and its salt of the present invention have high UV absorption ability over a wide ultraviolet wavelength region, and the structure of the compound itself has excellent stability, It can be effectively used as an ultraviolet absorber having excellent stability. Further, since the compound is excellent in water solubility, it can be blended into an aqueous base product. Therefore, by blending the compound, it is possible to obtain an ultraviolet ray absorbing composition and an external preparation for skin which are excellent in ultraviolet ray preventing effect and stability.
  • the furylmethylenemalonamide compound and salts thereof of the present invention do not absorb in the visible region, there is a change in appearance over time that is not colored when the compound is added to a product. I can't.
  • R, R and R are each independently a hydrogen atom or carbon number;! To 4 linear or branched
  • R and R each represent ⁇ (CH 2) - ⁇ -R, and R represents a hydrogen atom or
  • Carbon number represents a linear or branched alkyl group having from 4 to 4 carbon atoms.
  • m is an integer from 2 to 4, and n is an integer from 1 to 5.
  • R and R may be the same or different.
  • R, R, and R are each independently a hydrogen atom or a carbon number;!
  • R and R each represent ⁇ (CH) — ⁇ — R, and R represents a hydrogen atom Also
  • Examples of the straight chain or branched alkyl group having carbon atoms of! To 4 include methyl, ethyl, propyl, n-butyl, isopropyl group and the like.
  • R is preferably a hydrogen atom. Also,
  • R and R may be the same or different.
  • n is an integer of 1 to 5. In the present invention, it is preferable that m force is 3 and n is 2.
  • R and R are each ⁇ (CH 2) 10 ⁇ 1 H.
  • R, R, and R in the formula are the same as described above.
  • the furylmethylenemalonamide compound represented by the general formula (1) which is suitable for the present invention, can be produced using a known synthetic reaction.
  • the following is a representative force S for illustrating the production method S, and the present invention is not limited to this.
  • R, R, R, R, and R are the same as above.
  • the said manufacturing method 1 is demonstrated. As a first step, it has a substituent represented by the above general formula (7)! /, May! /, 2-furaldehyde (furfural), and represented by the above general formula (8).
  • malonic acid esters eg, jetyl malonate when R is an ethyl group
  • the compound represented by the above formula (9) can be synthesized. It is preferred to use about 1 equivalent of the compound of formula (8) in molar ratio to the compound of formula (7)! /.
  • 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.
  • 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 such an amount as to give a concentration in a usual synthesis reaction.
  • the mass ratio of the compound (7) is;
  • the amount of the reaction catalyst to be used may be in accordance with the amount of the catalyst for the normal reaction, for example, an amount of 0.01 to 0.9 in terms of 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).
  • Namide compounds can be synthesized.
  • the reaction temperature at this time is preferably 50 to 200 ° C.
  • R and R are the same for the compound of formula (9),
  • the compound of formula (9) is hydrolyzed to obtain a dicarboxylic acid of formula (10), and then amine NH.
  • R and / or NH-R can be easily synthesized by a known amide bond formation method.
  • a noremethylenemalonamide compound can be synthesized.
  • a furylmethylenmalonamide compound of the formula (1) can also be synthesized by adding a coupling reagent to the 2 4 2 5 solution for coupling.
  • a coupling reagent N, N′-dicyclohexylcarpositimide (DCC), N-hydroxysuccinimide and DCC, 1-hydroxybenzotriazole and DCC, etc. can be used.
  • malonic acid and amine NH 2 -R and / or NH 2 -R can be formed by known amide bond formation methods
  • R and R are different, first, react one of them in a molar ratio of about 1 equivalent.
  • the diamide compound of formula (11) and a 2-phenyl which may have a substituent may be used.
  • Lualdehyde furfural
  • the 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.
  • the reaction catalyst for example, piperidine, acetic acid, ammonium acetate and the like can be used alone or in combination.
  • the reaction solvent in an amount that provides a concentration in a normal synthesis reaction, for example, a mass ratio of 1 to 50 with respect to the compound (7).
  • the amount of the reaction catalyst to be used may be in accordance with the amount of the catalyst for the normal reaction, for example, an amount of 0.01 ⁇ 0.9 to 9 in molar ratio with respect to the compound of the formula (7).
  • the compounds of the formula (7) and (11) and the reaction catalyst are mixed in a reaction solvent and then refluxed to obtain the compound of the formula (1).
  • 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.), and jetyl malonate (manufactured by Wako Pure Chemical Industries Ltd.) ), 2- (2-aminoethoxy) ethanol (manufactured by Tokyo Chemical Industry Co., Ltd.) and the like 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, but examples of the inorganic salt include hydrochloride, sulfate, phosphate, hydrobromide, sodium salt, potassium salt, magnesium salt, calcium salt, ammonium salt, and the like. It is done.
  • Organic salts include acetate, lactate, maleate, fumarate, tartrate, kenate, methanesulfonate, P-toluenesulfonate, triethanolamine salt, diethanolamine salt, amino acid salt, etc. Can be mentioned.
  • the furyl methylene malonamide compound and / or salt thereof of the present invention is useful as an ultraviolet absorber.
  • a UV-absorbing composition can be prepared by blending a furylmethylenemalonamide compound and / or a salt thereof as an effective component and mixing with other various substances.
  • the ultraviolet absorber and the ultraviolet absorbing composition can be blended in various products that exhibit an ultraviolet absorbing effect.
  • the external preparation for skin containing the furylmethylenemalonamide compound and / or salt thereof of the present invention exhibits an excellent ultraviolet ray preventing effect and absorbs ultraviolet rays even under sun exposure. Since the agent does not decompose, the effect is stably exhibited over a long period of time. In addition, since it does not absorb the visible region, there is no change in appearance over time, which does not cause coloring of the product. Such a feature can be said to be an advantageous effect because changes in appearance over time tend to lead to a negative image of the effect that users sometimes expect. Furthermore, skin troubles occur, and it is extremely useful as an external preparation for skin especially for sunscreens.
  • an inorganic powder ultraviolet shielding agent in order to enhance the ultraviolet shielding effect, it is desirable to use an inorganic powder ultraviolet shielding agent together with an organic compound ultraviolet absorber.
  • makeup powders often contain inorganic powders.
  • an organic UV absorber when 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 with an external skin 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.
  • talc kaolin, boron nitride, mica, sericite (sericite), muscovite, biotite, phlogopite, synthetic mica, synthetic myth, permequilite, magnesium carbonate, calcium carbonate, anhydrous calcium, key Aluminum oxide, aluminum oxide, sodium silicate, calcium silicate, magnesium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate, calcined calcium, calcium phosphate, fluorapatite,
  • inorganic powders such as hydroxyapatite, ceramic powder, metal sarcophagus (zinc myristate, calcium palmitate, aluminum stearate, etc.), titanium dioxide, zinc oxide, iron oxide, iron titanate, carbon, low-order titanium oxide, Mango violet, cobalt violet
  • fine particle titanium oxide and fine particle zinc oxide are preferably added to sunscreen skin preparations such as sunscreen cosmetics.
  • the blending amount may be appropriately determined according to the desired ultraviolet absorbing ability. It is not limited to. Usually, it is preferably 0.00 to 20% by mass, more preferably 0.01 to 10% by mass with respect to the total amount of the external preparation for skin.
  • the blending amount of the inorganic powder is not limited. Appropriately determined according to the product for external preparation for skin, and usually about 0.;! To 99.5% by mass based on the total amount of external preparation for skin. For example, when preparing a skin external preparation for sunscreen, it is preferable that the inorganic powder is 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.
  • skin care cosmetics such as lotion, milky lotion, cream, beauty liquid, self-tanning agent, base cosmetics, makeup, lipstick, face color, eyeliner makeup cosmetics, hair spray, hair tonic
  • base cosmetics such as lotion, milky lotion, cream, beauty liquid, self-tanning agent, base cosmetics, makeup, lipstick, face color, eyeliner makeup cosmetics, hair spray, hair tonic
  • hair liquids and other cosmetics for hair and scalp examples include hair liquids and other cosmetics for hair and scalp.
  • the external preparation for skin of the present invention in addition to components that can be usually added to cosmetics and pharmaceuticals, for example, liquid oils, solid oils, waxes, hydrocarbons, higher fatty acids, higher alcohols. , Esters, silicones, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, humectants, water-soluble polymer compounds, thickeners, coating agents, sequestering agents, Lower alcohol, polyhydric alcohol, sugars, amino acids, organic amines, pH adjusters, skin nutrients, vitamins, antioxidants, fragrances, powders, coloring materials, water, etc. should be added as necessary. Can do.
  • the furylmethylenemalonamide compound and / or salt thereof of the present invention is incorporated into products other than skin external preparations, for example, paints, dyes, pigments, various resins, synthetic rubbers, latexes, finalenes, fibers and the like. Thus, it is possible to protect against ultraviolet rays.
  • the furylmethylene malonamide compound of the present invention and its salt or UV absorber are blended in various products,
  • an ultraviolet-absorbing composition by mixing with other raw material compounds or preparing an aqueous solution and blending it.
  • the amount of furylmethylenemalonamide compound and / or its salt in various products and UV-absorbing compositions is generally Normally 0 - 00;! ⁇ 20 mass 0/0, preferably 0. 01; 10 mass 0/0.
  • Example 1-1 2- (2-Furylmethylene) ⁇ 1. ⁇ ⁇ — Bis “2- (2-hydroxyethoxy) ethyl ⁇ Synthesis of malonamide
  • Jetyl malonate (3 ⁇ 59 mL, 23.78 mmol) and 2- (2 aminoethoxy) ethanol (5.00 g, 4.56 mmol) were stirred at 130 ° C. for 6 hours.
  • 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.
  • TMS Tetramethylsilane
  • Example 1 2 Synthesis of N N--bis “2- (2 hydroxyethoxy) ethyl ⁇ 2-” (5 methyl —2-furyl) methylene ⁇ malonamide
  • N 1 , N 3 bis [2- (2 hydroxyethoxy) ethinole] malonamide (0.70 g, 2.52 mm ⁇ 1) ⁇ ⁇ (6 mL), funolefuranol (0.25 mL, 2.52 mmol), piperidine ( 0.04 mL, 0.50 mmol) and acetic acid (0.09 mL, 1.51 mmol) were added. The reaction was refluxed for 3 hours, then allowed to cool and concentrated.
  • 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.
  • Evaluation 1 Measurement of absorbance in the ultraviolet wavelength region
  • the ultraviolet absorption spectrum (solvent: water, concentration lOppm, optical path length lcm) of the furylmethylenemalonamide compound of the present invention was measured with a spectrophotometer (V-560 manufactured by JASCO Corporation). 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).
  • the absorbance (solvent: water, optical path length 1 cm) of visible light at 405 nm of the furylmethylenemalonamide compound of the present invention was measured with a spectrophotometer (V-560 manufactured by JASCO Corporation). Further, as a comparative example, a conventional water-soluble ultraviolet absorber, 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone sodium, was also measured in the same manner. The results are shown in Table 2 below.
  • the furylmethylenemalonamide compound of the present invention does not absorb in the visible region longer than 400 ⁇ m. Therefore, the crystals were white and the aqueous solution was colorless and transparent.
  • the comparative compound since the comparative compound has absorption in the visible region, the crystals are colored light yellow and the aqueous solution is colored yellow. I can't expect.
  • the furylmethylenemalonamide compound of the present invention is excellent in solubility in water and can be blended at a high concentration.
  • 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 l— ZiN 1 , N 3 —Bis [2— (2-hydroxyethoxy) ethyl] 2 — [(5 Methyl-2-furyl) methylene] malonamide) and 2- hydroxy- 4- methoxysulfoxoni, a water-soluble UV absorber as a comparative example Umbenzo Sodium phenone was used.
  • An aqueous phase and an alcohol phase were prepared and mixed.
  • Propylene glycol and an ultraviolet absorber were added to ion-exchanged water and dissolved, and heated to 70 ° C (water phase).
  • the other ingredients were mixed, heated and melted and kept at 70 ° C (oil phase).
  • the oil phase was added to the water phase, pre-emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C while stirring well.
  • A More than 80% of subjects are effective or effective.
  • N 1 , N 3 Bis [2— (2-Hydroxy, colorless, transparent ethoxy) Eth / Le] —2 — [(5-Methinole, colorless, transparent — 2-furyl) methylene] malonamide, colorless, transparent
  • the external preparation for skin containing the furylmethylenemalonamide compound of the present invention has an excellent anti-ultraviolet effect compared to the case where a conventional water-soluble ultraviolet absorber is added. Had. Moreover, no precipitation of the UV absorber was observed even at low temperature storage.
  • the furylmethylenemalonamide compound of the present invention has excellent absorbability in the ultraviolet wavelength region where water solubility is extremely high.
  • the furylmethylenemalonamide compound of the present invention is used as a water-soluble ultraviolet absorber. It is a very useful compound.
  • 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 an external preparation for skin. Went.
  • a 24-hour occlusion patch test was performed 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.
  • the average score obtained by dividing the total score of the 20 people by the number of people was determined and judged according to the following criteria.
  • the average score is 1 or more and less than 2.
  • the average score is 2 or more.
  • N 1 , N 3 Bis [2— (2-Hydroxy Lotion A Ethoxy) Ethyl] —2 — [(5 Methyl Cream A
  • N 1 , N 3 Bis [2— (2-Hydroxy A Colorless Transparent A Ethoxy) Ethinole] _2 _ [(5-Methinore
  • the furylmethylenemalonamide compound of the present invention is not decomposed even by exposure to direct sunlight for a long time as compared with the conventional water-soluble ultraviolet absorber, and has a very high residual rate. Indicated.
  • Evaluation 7 Stability test when combined with inorganic powder external shielding agent
  • the conventional water-soluble ultraviolet absorbers have the ability of yellowing when the inorganic powder is used together, and the skin external preparation containing the furylmethylenemalonamide compound of the present invention is inorganic. No discoloration was observed even when the powder was used in combination.
  • the furylmethylenemalonamide compound of the present invention is excellent in light stability with no skin irritation and does not cause discoloration when used in combination with inorganic powder.
  • the ultraviolet absorbent according to the present invention is very useful as an ultraviolet absorbent that can be blended in an external preparation for skin.
  • the water phase component was added to ion-exchanged water to dissolve it, and it was heated and kept at 70 ° C (water 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 term.
  • aqueous phase component was added to ion-exchanged water to dissolve it, and heated to 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 water 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 term.
  • Propylene glycol and N 1 , N 3 -bis [2- (2-hydroxyethoxy) ethyl] -2-2-[(5 methyl-2-furyl) methylene] malonamide are dissolved in ion-exchanged water, heated to 70 ° C maintained (aqueous phase).
  • the other ingredients 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.
  • Carboxybule polymer was dissolved in a small amount of ion-exchanged water (A phase).
  • a phase ion-exchanged water
  • the aqueous phase component was added to the remainder of the ion exchange water, dissolved by heating and kept at 70 ° C (aqueous phase).
  • the other ingredients 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.
  • Carboxybule polymer was dissolved in a small amount of ion-exchanged water (A phase).
  • a phase ion-exchanged water
  • the aqueous phase component was added and dissolved by heating and kept at 70 ° C (aqueous phase).
  • the other ingredients 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.
  • Carboxybule 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 intended jewel.
  • Carboxybule polymer was uniformly dissolved in ion-exchanged water (A phase). 95% ethanol POE (50) oleyl ether was dissolved in the solution and added to Phase A. After adding components other than sodium hydroxide, sodium hydroxide was added to neutralize and thicken to obtain the intended jewel.
  • phase and C phase were uniformly dissolved, and solubilized by adding A phase to C phase.
  • Phase B was added and mixed to obtain the desired serum.
  • phase and C phase were uniformly dissolved, and solubilized by adding A phase to C phase. Then phase B And mixed to obtain the desired serum.
  • a phase, B phase, and C phase were uniformly dissolved, and B phase was added to A phase to solubilize. This was then added to Phase C and mixed to obtain the desired pack.
  • phase, B phase, and C phase were uniformly dissolved, and B phase was added to A phase to solubilize. This is then added to Phase C and mixed to obtain the desired
  • 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.
  • the components (1) to (8) were mixed and ground. To this, a mixture of the components (9) to (; 15) was added and stirred and mixed. This was molded into a container to obtain the desired solid:
  • the components (1) to (8) were mixed and ground. This is a mixture of the components (9) to (; 15) Were mixed with stirring. This was molded into a container to obtain the desired fixation.
  • the components (11) to (21) were uniformly mixed and dissolved. To this, mixed and crushed (1) to (7) In addition, it was 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.
  • the components (1) to (6) were mixed and ground. To this, a mixture of components (7) to (; 13) was added and mixed by stirring to obtain the desired white powder.
  • the components (1) to (6) were mixed and ground. To this, a mixture of components (7) to (; 13) was added and mixed with stirring to obtain the desired eye shadow.
  • Formulation example 27 hair foam
  • 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 into the can, and after filling the valve, gas was filled.
  • N 1 , N 3 Bis [2- (2-hydroxyethoxy) ethinole]

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Abstract

L'invention concerne un composé de furylméthylènemalonamide, lequel est hautement soluble dans l'eau, présente une excellente absorption dans la région des longueurs d'ondes des rayons ultraviolets mais pas d'absorption dans la région du visible et a une excellente stabilité. L'invention concerne précisément un composé de furylméthylènemalonamide représenté par la formule générale (1) ou un sel de celui-ci. (1) [Dans la formule, R1, R2 et R3 représentent chacun indépendamment un atome d'hydrogène ou un groupe alkyle linéaire ou ramifié ayant 1 à 4 atomes de carbone ; R4 et R5 représentent chacun indépendamment un groupe [(CH2)m-O]n-R6 où R6 représente un atome d'hydrogène ou un groupe alkyle linéaire ou ramifié ayant 1 à 4 atomes de carbone ; m représente un nombre entier de 2 à 4 ; et n représente un nombre entier de 1 à 5, à condition que R4 et R5 puissent être identiques ou différents.]
PCT/JP2007/068434 2006-10-04 2007-09-21 Composé de furylméthylènemalonamide et sel de celui-ci, absorbeur des rayons ultraviolets et préparation externe pour la peau WO2008041525A1 (fr)

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JP2006-272614 2006-10-04
JP2006272614A JP5022659B2 (ja) 2006-10-04 2006-10-04 フリルメチレンマロンアミド化合物及びその塩、紫外線吸収剤、皮膚外用剤

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022254168A1 (fr) * 2021-06-04 2022-12-08 Institut Des Sciences Et Industries Du Vivant Et De L'environnement - Agroparistech Nouvelles molecules derivees de furanacrylates et 5-hydroxymethyl furanacrylates presentant des proprietes filtre uv-b

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5262560B2 (ja) * 2008-10-17 2013-08-14 株式会社Ｉｈｉ 化粧料及び化粧料の製造方法
JP5546140B2 (ja) * 2009-02-16 2014-07-09 株式会社 資生堂 水中油型乳化組成物

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0100651A1 (fr) * 1982-08-03 1984-02-15 VAN DYK & COMPANY, INC. Malonates de dialkyle en tant qu'adjuvants organiques pour écrans solaires
WO2005037196A2 (fr) * 2003-10-06 2005-04-28 Cytovia, Inc. Malonamides 2-arylmethylene-n-aryl-n'-aryl substitues et leurs analogues utiles comme activateurs des caspases et inducteurs de l'apoptose
WO2005118676A1 (fr) * 2004-05-27 2005-12-15 Eastman Chemical Company Absorbeurs de rayons ultraviolets au furyl-2-methylidene et compositions renfermant lesdits absorbeurs de rayons ultraviolets

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0100651A1 (fr) * 1982-08-03 1984-02-15 VAN DYK & COMPANY, INC. Malonates de dialkyle en tant qu'adjuvants organiques pour écrans solaires
WO2005037196A2 (fr) * 2003-10-06 2005-04-28 Cytovia, Inc. Malonamides 2-arylmethylene-n-aryl-n'-aryl substitues et leurs analogues utiles comme activateurs des caspases et inducteurs de l'apoptose
WO2005118676A1 (fr) * 2004-05-27 2005-12-15 Eastman Chemical Company Absorbeurs de rayons ultraviolets au furyl-2-methylidene et compositions renfermant lesdits absorbeurs de rayons ultraviolets

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022254168A1 (fr) * 2021-06-04 2022-12-08 Institut Des Sciences Et Industries Du Vivant Et De L'environnement - Agroparistech Nouvelles molecules derivees de furanacrylates et 5-hydroxymethyl furanacrylates presentant des proprietes filtre uv-b
FR3123564A1 (fr) * 2021-06-04 2022-12-09 Institut Des Sciences Et Industries Du Vivant Et De L'environnement - Agroparistech Nouvelles molecules derivees de furanacrylates et 5-hydroxymethyl furanacrylates presentant des proprietes filtre uv-b et/ou antimicrobiennes

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