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WO2010125092A1 - Composés 3-dialkylaminophényl 2-alcoxycarbonylbenzoïque - Google Patents

Composés 3-dialkylaminophényl 2-alcoxycarbonylbenzoïque Download PDF

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Publication number
WO2010125092A1
WO2010125092A1 PCT/EP2010/055697 EP2010055697W WO2010125092A1 WO 2010125092 A1 WO2010125092 A1 WO 2010125092A1 EP 2010055697 W EP2010055697 W EP 2010055697W WO 2010125092 A1 WO2010125092 A1 WO 2010125092A1
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Prior art keywords
branched
linear
compound
sunscreen
alkyl
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English (en)
Inventor
Juan Sallares Rosell
Santiago Nonell
Francisco Marquillas Olondriz
Ricardo Miralles
Adaya GALLARDO SÁNCHEZ
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Interquim SA
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Interquim SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41—Amines
    • A61K8/411—Aromatic amines, i.e. where the amino group is directly linked to the aromatic nucleus
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C219/34—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having amino groups and esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton

Definitions

  • the main object of this invention is to provide novel 3- dialkylaminophenyl 2-alkoxycarbonylbenzoic compounds. These compounds may be progressively transformed into stable sunscreens by the application of the photo-Fries transposition; in addition, their industrial scale production is feasible and inexpensive.
  • the compounds of the invention provide either a progressive sunscreen action against UV radiation or an indicative action of the amount of UVB radiation received; both of these actions depending on the duration and degree of sun exposure.
  • the present invention relates to photochemical precursors of ultraviolet absorbents, particularly 3-dialkylaminophenyl 2-alkoxycarbonylbenzoic compounds, as well as their preparation and their use as progressive sunscreens against UV radiation.
  • UV A ultraviolet A
  • UVB ultraviolet B
  • a sunscreen is any substance or material that protects the skin from UV radiation.
  • Sunscreens are available in the form of topical lotion, cream, ointment, gel, or spray that can be applied to the skin; salve or stick that can be applied to lips, nose and eyelids; moistener in towelettes that can be rubbed against the skin; sunglasses that protect the eyes; and film screen that can be affixed to the windows of car, room or office.
  • UVA may be just as dangerous as UVB, although its effects may take longer to show up.
  • UVA may play a role in causing melanoma.
  • Most sunscreen products contain ingredients that provide adequate protection only against UVB rays. Even those labeled as "broad-spectrum" sunscreens may offer only partial protection against UVA radiation. Those containing the active ingredient avobenzone (4-te/t-butyl-4'-methoxydibenzoylmethane) give the most protection against UVA rays.
  • Sunscreens should be applied between 30 minutes and 2 hours before sun exposure. In general, they should be reapplied after every 80 minutes spent in the water or when perspiring heavily or every 2 hours spent out of the water.
  • UVB 290-320 nm
  • SPDF Sun Protection Factor
  • UVR ultraviolet radiation
  • MED minimal erythema dose
  • the SPF represents the length of time that sunscreen-protected skin can be exposed to UV rays before a minimal redness (erythema) appears, compared to the length of time it takes on unprotected skin. In other words, it indicates how much longer the skin can be exposed to the sun before getting sunburned. For example, without a sunscreen, an individual might get a sunburn after 20 minutes or less in the sun. By applying a sunscreen of SPF 15, the individual might spend up to 300 minutes in the sun before getting sunburned that is 15 times longer that if no protection is used.
  • Sunscreens with an SPF higher than 15 may be effective in fair-skinned people who live at high altitudes, either work or play outdoors much of the day, or perspire heavily. swimming and perspiration reduce the actual SPF value of many sunscreens, even those that are water-resistant, so it is convenient to reapply the product often.
  • Table 1 shows some relevant widely used sunscreen compounds. Table 1
  • Dioxybenzone (2,2'-dihydroxy-4-methoxybenzophenone, US2853521 ) is mainly used as an UV absorber for polymers and coatings. It is used as a stabilizer for polyester film. It is effective against UVB light and some UVA range.
  • Oxybenzone (2-hydroxy-4-methoxybenzophenone, US2773903, US2861104, US2861105 and US3073866) absorbs well through UVA Il rays and can be considered a broad-spectrum absorber. It enhances UVB protection when used in a given formula.
  • Sulisobenzone (5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid, GB1136525) extends coverage beyond the wavelength range of UVB rays and into the wavelength range UVA rays, from which broad-spectrum sunscreen preparations are obtained.
  • Amino-substituted hydroxybenzophenones have been disclosed as photostable UV filters to be used in cosmetic and dermatological compositions (US6409995).
  • Chemical sunscreens "block" the penetration of UV radiation through the epidermis by acting as filters and absorbing and reflecting high-energy UV radiation.
  • Sunscreen molecules absorb high-energy UV photons causing the electronic structure to move to a higher energy state. This electronic energy is dissipated by conversion to vibrational and rotational energy within the molecule, ultimately being transferred to the molecule's environment as heat.
  • SPF SPF
  • SPF 25 sunscreen may be the best choice for high risk individuals, especially when sun exposure is expected to be extensive. Rubbing, sweating, and water immersion diminish the effectiveness of all sunscreens, requiring frequent re- application of the product even with supposedly waterproof or sweat proof formulations. Another factor which enhances the damaging effects of lengthy exposures is a time-dependent diminution of SPF effect not related to removal of the product from rubbing or washing.
  • SPF 25 sunscreen are frequently inadequate to prevent erythema, and that multiple applications are required to completely suppress erythema, even from a single day's sun exposure.
  • a significant multi-day exposure to sunlight e.g., all day Saturday and Sunday
  • the sunscreen functions as predicted by the rated SPF to prevent erythema on the first day of exposure
  • the heightened sensitivity on the second and subsequent days of exposure may lead to erythema development which would not have been predicted as based solely on extrapolations of the SPF.
  • a sunscreen with an SPF > 30 may provide significantly better protection from UV damage, particularly in susceptible individuals
  • SPF testing is designed to evaluate protection against erythema produced by natural sunlight, and therefore denotes principally the degree of protection against UVB, since the amount of UVA received from sunlight does not produce significant erythema.
  • the only ingredient approved by the FDA for protection against UVA radiation is avobenzone.
  • a product contains ingredients that absorb UV between 290-320 nm it can be labeled as a broad-spectrum sunscreen, meaning it will provide protection against both UVB and short wave UVA radiation.
  • Adverse reactions to sunscreens comprise skin problems, such as allergic contact reactions, photocontact reactions, and drying or tightening of the skin.
  • Other side effects are rare, but possible, namely, acne, burning, itching, or stinging of the skin, redness or swelling of the skin, rash, with or without blisters that ooze and become crusted, pain in hairy parts of body and pus in hair follicles.
  • Photostability refers to the ability of a molecule to remain intact with irradiation. Photostability is potentially a problem with all UV filters because they are deliberately selected to be UV radiation-absorbing molecules. This issue has been raised specifically with avobenzone; photolysis has been demonstrated, specially, in in vitro systems that simultaneously irradiate and measure transmittance in situ. The photostability of the molecules also depends on the solvent or the vehicle used.
  • Patent WO2006100225 discloses some benzoic esters with ultraviolet absorbing properties per se. These compounds are capable of being photochemically transformed in situ into other conventional sunscreen compounds with higher UV protection, such as dioxibenzone, oxybenzone, sulisobenzone, 4-diethylamino-2-hydroxybenzophenone and 2-hydroxy-4-(1- pyrrolidinyl)benzophenone, which allows their use in the protection of humans or animals against ultraviolet radiation. These compounds may be defined as progressive sunscreens because of their progressive transformation into more potent sunscreens depending on the amount of solar radiation received.
  • the present invention provides novel useful compounds as progressive sunscreens against UV radiation, which are transformed in situ into known stable sunscreens -such as hexyl 2-(4-diethylamino-2-hydroxybenzoyl)- benzoate- by the application of the photo-Fries transposition.
  • known stable sunscreens such as hexyl 2-(4-diethylamino-2-hydroxybenzoyl)- benzoate- by the application of the photo-Fries transposition.
  • the compound which is most structurally similar to the compounds of the present invention is
  • the new compounds provide the additional advantage that their industrial scale production is feasible and inexpensive due to their structure derived from phtalic acid.
  • FIG. 1A represents the spectral changes observed during exposure of 3-diethylaminophenyl 2-hexanoxycarbonylbenzoate (II) to increasing doses of UV-B radiation. See example 3 for details.
  • FIG. 1 B shows the kinetics of the phototransposition of 3- diethylaminophenyl 2-hexanoxycarbonylbenzoate (II) into hexyl 2-(4- diethylamino-2-hydroxybenzoyl)benzoate (Xl). See example 3 for details.
  • the present invention relates to 3-dialkylaminophenyl 2- alkoxycarbonylbenzoic compounds of formula (I)
  • R is selected from hydrogen, linear or branched (Ci-Ci 2 )alkyl and (C 5 - C 7 )cycloalkyl;
  • Ri and R2 are independently selected from hydrogen and linear or branched (CrC6)alkyl, or else RrR 2 form a (CH 2 ) n group where n is 4-6; and
  • R 3 -R 9 are independently selected from hydrogen, linear or branched (d- C 4 )alkyl and linear or branched (Ci-C 4 )alkoxy; with the proviso that when RrR ⁇ and R S -R ⁇ are each hydrogen and R 7 is methyl, R cannot simultaneously be hydrogen; or a topically acceptable salt thereof.
  • Preferred compounds are 3-dialkylaminophenyl 2- alkoxycarbonylbenzoic compounds (I) when R is linear or branched (d- Ci 2 )alkyl and (C 5 -C 7 )cycloalkyl.
  • Preferred compounds are 3-dialkylaminophenyl 2- alkoxycarbonylbenzoic compounds (I) when both Ri and R 2 are linear or branched (CrC6)alkyl, similar or not, or else RrR 2 form a (CH 2 ) n group wherein n is 4-6.
  • a particularly preferred compound is 3-diethylaminophenyl 2- hexanoxycarbonylbenzoate of formula (II)
  • topically acceptable salt used herein includes any salt formed from organic and inorganic acids, such as hydrobromic, hydrochloric, phosphoric, nitric, sulfuric, acetic, adipic, aspartic, benzenesulfonic, benzoic, citric, ethanesulfonic, formic, fumaric, glutamic, lactic, maleic, malic, malonic, mandelic, methanesulfonic, 1 ,5-naphthalendisulfonic, oxalic, pivalic, propionic, p-toluenesulfonic, succinic, tartaric acids and the like.
  • organic and inorganic acids such as hydrobromic, hydrochloric, phosphoric, nitric, sulfuric, acetic, adipic, aspartic, benzenesulfonic, benzoic, citric, ethanesulfonic, formic, fumaric, glutamic, lactic, maleic,
  • Ri, R 2 , R 7 , Rs and Rg have the same meaning as in (I), by means of a dehydrating agent selected from dicyclohexylcarbodiimide, N 1 N'- carbonylimidazole and linear or branched (Ci-C ⁇ jalkyl chloroformates, in the presence of an organic or inorganic base.
  • a dehydrating agent selected from dicyclohexylcarbodiimide, N 1 N'- carbonylimidazole and linear or branched (Ci-C ⁇ jalkyl chloroformates, in the presence of an organic or inorganic base.
  • R, R 3 , R 4 , R 5 and Re have the same meaning as in (I) and X is chlorine or bromine, is reacted with substituted 3-dialkylaminophenol of formula (IV)
  • Another object of the present invention is to provide the use of a 3- dialkylaminophenyl 2-alkoxycarbonylbenzoic compound (I')
  • R is selected from hydrogen, linear or branched (Ci-Ci 2 )alkyl and (C 5 -
  • Ri and R 2 are independently selected from hydrogen and linear or branched
  • R r R 2 form a (CH 2 ) n group where n is 4-6; and R 3 -R 9 are independently selected from hydrogen, linear or branched (d-
  • R is selected from hydrogen, linear or branched (Ci-Ci 2 )alkyl and (C 5 - C 7 )cycloalkyl; Ri and R2 are independently selected from hydrogen and linear or branched (Ci-C 6 )alkyl, or else R r R 2 form a (CH 2 ) n group where n is 4-6; and R 3 -R 9 are independently selected from hydrogen, linear or branched (d- C 4 )alkyl and linear or branched (Ci-C 4 )alkoxy; or a topically acceptable salt thereof together with one or more topical excipients or carriers.
  • the topical composition of the present invention can be applied both to pets and humans.
  • the composition is characterized in that the proportion of 3-dialkylaminophenyl 2-alcoxycarbonylbenzoic compound (I') ranges from 0.01 % to 40 % by weight. More preferably the range is from
  • the range is from 0.05% to 15%. In a more preferred embodiment, the range is from 5% to 15%.
  • the composition is characterized in that the dosage form is selected from cream, ointment, milk, suspension, powder, oil, lotion, gel, stick, foam, emulsion, dispersing agent, spray, aerosol, lip stick, base cream, make-up, disperse or compact powder, rouge, eyeshadow, mask, nail-varnish, nail-polish and non-permanent hair dye.
  • the dosage form is selected from cream, ointment, milk, suspension, powder, oil, lotion, gel, stick, foam, emulsion, dispersing agent, spray, aerosol, lip stick, base cream, make-up, disperse or compact powder, rouge, eyeshadow, mask, nail-varnish, nail-polish and non-permanent hair dye.
  • compositions are characterized in that they additionally comprise a second sunscreen compound.
  • the second sunscreen compound is selected from the group consisting of avobenzone, 2-ethylhexyl-p- methoxycinnamate, oxybenzone, octyldimethyl p-aminobenzoic acid, dioxybenzone, ethyl-4-[bis(hydroxypropyl)]aminobenzoate, 2-ethylhexyl-2- cyano-3,3-diphenylacrylate, 2-ethylhexylsalicylate, glycerol p-aminobenzoate, 3,3,5-trimethylcyclohexylsalicylate, methylantranilate, p-dimethylaminobenzoic acid, 2-ethylhexyl p-dimethylaminobenzoate, 2-phenylbenzimidazole-5- sulfonic acid, 2-p-dimethylaminophenyl-5-sulfoniobenzoxazoic acid,
  • the proportion of the second sunscreen compound ranges from 0.01 % to 40 % by weight. More preferably, the range is from 0.05% to 25 %, and even more preferably the range is from 0.05% to 15%.
  • 3-dialkylaminophenyl 2- alkoxycarbonylbenzoic compounds (I') are interesting properties that they can photostabilize several ingredients of the compositions against solar radiation. This aspect is especially significant in those compounds comprising a second sunscreen compound, whose photochemical degradation is thus prevented or diminished.
  • the composition is characterized in that the dosage form is selected from cream, ointment, milk, suspension, powder, oil, lotion, gel, stick, foam, emulsion, dispersing agent, spray, aerosol, and lip stick.
  • compositions of the present invention may contain one or more additional organic sunscreen agents for filtering UVB or UVA rays or they may additionally contain one or more metal oxide sunscreen agents such as titanium dioxide or zinc oxide.
  • the composition may also contain a carrier and at least one component selected from the group consisting of dispersing agents, preservatives, anti-foams, perfumes, fragrances, oils, waxes, propellants, dyes, pigments, emulsifiers, surfactants, thickeners, humectants, exfoliants and emollients.
  • These sunscreen compositions may be in the form of a cosmetic composition with a cosmetically acceptable carrier and one or more cosmetic adjuvants.
  • the sunscreen composition can optionally include conventional antioxidants or other stabilizers without UV absorbing characteristics.
  • ingredients and other ingredients described more particularly below are generally used in an amount from about 0.1 % to about 10% by weight of the sunscreen composition, together with cosmetically or pharmaceutically acceptable carriers.
  • Suitable dispersing agents for the sunscreen compositions include those useful for dispersing organic or inorganic sunscreen agents in water phase, oil phase, or part of an emulsion, including, for example, chitosan.
  • Emulsifiers may be used in the sunscreen compositions to disperse one or more of the compounds of formula (I) or other components of the sunscreen composition.
  • Suitable emulsifiers include conventional agents such as, for example, glycerol stearate, stearyl alcohol, cetyl alcohol, dimethicone copolyol phosphate, hexadecyl-D-glucoside, octadecyl-D-glucoside, etc
  • Thickening agents may be used to increase the viscosity of the sunscreen compositions.
  • Suitable thickening agents include carbomers, acrylate/acrylonitrile copolymers, xanthan gum and combinations thereof.
  • the carbomer thickeners include the crosslinked acrylic polymers.
  • the amount of thickener within the sunscreen formulation, on a solid basis without water may range from about 0.001 to about 5%, preferably from 0.01 to about 1 % and optimally from about 0.1 to about 0.5% by weight.
  • sunscreen compositions to be applied to skin or hair may include preservatives, waterproofing agents, fragrances, anti-foam agents, plant extracts (aloe vera, witch hazel, cucumber, etc) opacifiers, skin conditioning agents and colorants, each in effective amounts to accomplish their respective functions.
  • the sunscreen compositions may optionally contain an ingredient which enhances the waterproof properties such as compounds that form a polymeric film, such as dimethicone copolyol phosphate, diisostearoyl trimethylolpropane siloxysilicate and dilauroyl trimethylolpropane siloxysilicate, chitosan, dimethicone, polyethylene, polyvinylpyrrolidone (PVP), PVP/vinylacetate, PVP/eiconsene copolymer, adipic acids/diethylene glycol/glycerine crosspolymer and the like.
  • Waterproofing agents may be present at levels of from about 0.01 to about 10% by weight.
  • the sunscreen compositions may also optionally contain one or more skin conditioning agents. These include humectants, exfoliants and emollients.
  • Humectants are polyhydric alcohols intended for moisturizing, reducing scaling and stimulating the removal of built scale from the skin.
  • polyhydric alcohols include polyalkylene glycols and more preferably alkylene polyols and their derivatives.
  • Illustrative are propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, 2-pyrrolidone-5- carboxylate, hydroxypropyl sorbitol, hexylene glycol, ethoxydiglycol 1 ,3- butylene glycol, 1 ,2,6-hexanetriol, glycerin, ethoxylated glycerin, propoxylated glycerin and mixtures thereof.
  • the humectant is glycerin.
  • Amounts of humectant can range anywhere from 1 to 30%, preferably from 2 to 20% and optimally from about 5 to 10% by weight of the sunscreen composition.
  • Suitable exfoliants for use in the present invention may be selected from alpha-hydroxy carboxylic acids, beta hydroxycarboxylic acids and salts of these acids. Most preferred are glycolic, lactic and salicylic acids and their alkali, metal or ammonium salts.
  • Suitable emollients include those agents known for softening the skin or hair which may be selected from hydrocarbons, fatty acids, fatty alcohols and esters.
  • Petrolatum is a common hydrocarbon type of emollient conditioning agent.
  • Other hydrocarbons that may be employed include alkyl benzoates, mineral oils, polyolefins such as polydecene, and paraffin, such as isohexadecane.
  • Fatty acids and alcohols typically have from about 10 to 30 carbon atoms. Illustrative are myristic, isostearic, hydroxystearic, oleic, linoleic, ricinoleic, behenic and eruicic acids and alcohols.
  • Oily ester emollients may be those selected from one or more of the following triglyceride esters, acetoglyceride esters, ethoxylated glycerides, alkyl esters of fatty acids, ether esters, polyhydric alcohol esters and wax esters.
  • Additional emollients or hydrophobic agents include C12 to C15 alkyl benzoates, dioctyladipate, octyl stearate, octyldodecanol, hexyl laurate, octyldodecyl neopentanoate, cyclomethicone, dicapryl ether, dimethicone, phenyl trimethicone, isopropyl myhstate, caprylic/caphc glycerides, propylene glycol dicaprylate/dicaprate and decyl oleate.
  • the sunscreen compositions may optionally contain one or more inorganic sunscreen agents as discussed above including micro fine surface treated titanium dioxide and micro fine untreated and surface treated zinc oxide.
  • Titanium dioxide in the sunscreen compositions preferably has a mean primary particle size of between 5 and 150 nm and preferably from 10 to 100 nm.
  • the zinc oxide in the sunscreen compositions preferably has a mean primary particle size of between 5 nm and 150 nm, preferably between 10 nm and 100 nm.
  • the sunscreen compositions may also contain one or more additional monomeric organic chromophohc compounds. These can either be UVA, UVB or broad band filters.
  • suitable UVA sunscreens include benzophenone derivatives, menthyl anthranilate, butyl methoxydibenzoyl methane and benzylidene-dioxoimidazoline derivatives. Examples of suitable
  • UVB sunscreens include cinnamate derivatives, salicylate derivatives, p- aminobenzoic acid derivatives, camphor derivatives, phenylbenzimidazole derivatives and diphenylacrylate derivatives.
  • suitable broad-band sunscreen include benzotriazole derivatives and thazine derivatives such as anisotriazone. Others include ethylhexyltriazone and diethylhexylbutamidotriazone.
  • organic sunscreen agents that can be introduced are avobenzone, 2-ethylhexyl p-methoxycinnamate, oxybenzone, octyldimethyl p-aminobenzoic acid, dioxybenzone, ethyl-4- [bis(hydroxypropyl)]aminobenzoate, 2-ethylhexyl-2-cyano-3,3- diphenylacrylate, 2-ethylhexylsalicylate, glycerol p-aminobenzoate, 3,3,5- trimethylcyclohexylsalicylate, methylanthranilate, p-dimethylaminobenzoic acid, 2-ethylhexyl p-dimethylaminobenzoate, 2-phenylbenzimidazole-5- sulfonic acid, 2-p-dimethylaminophenyl-5-sulfoniobenzoxazoic acid, sulisobenzone,
  • Examples of useful commercially available organic sunscreen agents that can be introduced include 2-phenylbenzimidazole-5- sulphonic acid, 2-(4-methylbenzylidene)-camphor and 4- isopropyldibenzoylmethane.
  • the sunscreen formulation may contain an additional antioxidant.
  • suitable antioxidants which provide stability include p-hydroxybenzoic acid and its esters, salicylates, cumarin derivatives, flavones, hydroxy or methoxy substituted benzophenones, uric or tannic acid and its derivatives, hydroquinone, and benzophenones.
  • the total sum of the percentages in weight of each one of the ingredients selected to manufacture the topical composition will be of 100%.
  • pigments are being sought which are capable of imparting to these various types of products a varied palette of colorations which are reproducible over time and are insoluble in most of the cosmetic media used such as water and cosmetically acceptable solvents. These pigments should, moreover, be stable at the pHs usually used or encountered in the cosmetics field.
  • Cosmetic or pharmaceutical products such as skin lotions, collagen creams, sunscreen, facial make-up, etc.
  • synthetic materials such as antifoams, antioxidants, antiperspirants, colorants, dyes, emollients, emulsifiers, exfoliants, humectants, lipids, moisturizers, perfumes, fragrances, pigments, preservatives, propellants, skin conditioners, solvents, surfactants, thickeners, water proofing agents, etc.; as well as natural products such as collagen, proteins, mink oil, olive oil, coconut oil, carnauba wax, beeswax, lanolin, cocoa butter, xanthan gum, aloe, etc.
  • the cosmetic, pharmaceutical and personal care compositions can be in the form of creams, ointments, milks, suspensions, powders, oils, lotions, gels, sticks, foams, emulsions, dispersions, sprays and aerosols, and the like. More specific forms include lipsticks, foundations, makeup, disperse or compact powders, eye blushes, eye shadows, mascaras, nail varnishes, nail lacquers and non permanent hair dye, and the like.
  • the resulting mixture was heated to 100 0 C for 2 hours, and a transparent and homogeneous solution was obtained; total transformation of phtalic anhydride was observed by thin-layer chromatography (Cl 3 CH:AcOEt; 80:20).
  • the obtained solution was cooled to 10-15 0 C and 975 ml_ of an aqueous solution of 6N hydrochloric acid was slowly added.
  • the resulting two phases were separated by decantation. To the higher organic phase were added 1200 ml_ of water and basified with about 500 ml_ of an aqueous solution of 20% sodium carbonate until pH 8-9.
  • the lower aqueous phase which contained the sodium salt of product (VII) was decanted, diluted with 450 ml_ of toluene, and acidified with about 200 ml_ of an aqueous solution of 6N hydrochloric acid until pH 4-5.
  • the resulting two phases were separated by decantation, and the higher organic phase with acid (VII) was concentrated under reduced pressure to dryness. 360 g (yield 96%) of 2- hexanoxycarbonylbenzoic compound (VII) were obtained as yellowish oil. Purity was higher than 99%, which is high enough to be used in the following step.
  • Phototransformation of 3-diethylaminophenyl 2-hexanoxycarbonylbenzoate (II) was achieved by exposing 3 ml_ of a 0.018 mg/mL solution of this compound in methanol to UV-B radiation in a Luzchem LZC-4 photoreactor equipped with 20 16 broad band UV-B lamps (LES-UVB-01 ) at 35 0 C.
  • the solution was contained in a 1 x 1 cm standard quarz fluorescence cuvette (Hellma) during the experiments.
  • the absorbance spectrum of the sample was recorded using a Varian Cary-4E UV-Vis spectrophotometer.
  • the irradiance of the UVB source was 70 W/m2.
  • FIG. 1A shows the spectral changes observed upon phototransposition of 3-diethylaminophenyl 2- hexanoxycarbonylbenzoate (II) into hexyl 2-(4-diethylamino-2- hydroxybenzoyl)benzoate (Xl).
  • FIG. 1 B shows the kinetics of the process as absorbance changes at 260 nm and 355 nm.
  • the in vitro sunscreen activity of 3-diethylaminophenyl 2- hexanoxycarbonylbenzoate (II) was determined at 3% in polydimethylsyloxane.
  • Compound (II) formed a cream with sun protection factor (SPF) 1.0, which is classified as moderate and without protection against UVA.
  • SPDF sun protection factor
  • the SPF value increases up to 1.6 and achieves maximum UVA protection according to Boots star rating system.
  • the compound referred as "active ingredient” or “active ingredient 1 " is the compound of Example 2 of the present invention (3-diethylaminophenyl 2-hexanoxycarbonylbenzoate); the compound referred as “active compound 2” is avobenzone; and the compound referred as “active compound 3 " is dioxibenzone.
  • Phase B The ingredients of Phase B were combined, and the mixture was stirred and heated to 70-75 0 C.
  • the ingredients of Phase A were combined, and the mixture was heated to 70-75 0 C under stirring.
  • Phase B was added to Phase A under stirring.
  • Preservative was added. The mixture was stirred and left to cool at room temperature.
  • Composition Example 2 Sunscreen spray lotion (oil/water)
  • A-1 ingredients were combined, and the mixture was stirred and heated to 6O 0 C until dissolution of all solids.
  • A-2 ingredients were dispersed in A-1 ingredients under stirring.
  • B-1 ingredients were combined; the mixture was stirred and heated to 6O 0 C.
  • B-2 ingredients were dispersed in B-1 ingredients under stirring.
  • A was added to B while vigorously stirring.
  • the mixture was softly homogenized and left to cool to 4O 0 C.
  • C was added to A/B; the mixture was softly homogenized until it becomes uniform.
  • the mixture was stirred with another mixer and left to reach 25 0 C before packaging. Dosage was conveniently performed by means of a high-safety spray pump device.
  • composition Example 3 Sunscreen cream
  • Phase B 2 Finsolv® TN (Finetex)
  • Phase A The ingredients of Phase A were mixed in a large container under jet stirring. The mixture was heated to 75-8O 0 C. The ingredients of Phase B were combined; the suspension was mixed and heated to 85 0 C. Phase B was slowly added to the preparation and mixed for 15 minutes at 85 0 C. The mixture was removed from heat, transferred to a mixer and cooled at room temperature.
  • Composition Example 4 Broad-spectrum sunscreen lotion (water/oil)
  • Active ingredient 2 5.00%
  • composition Example 5 UVA/UVB sunscreen cream with Avobenzone
  • Phase A-1 The ingredients of Phase A-1 were combined; the mixture was heated to 5O 0 C under stirring until dissolution of methylparaben.
  • Phase A-2 was incorporated into Phase A-1 using a sieve.
  • the resulting mixture A was heated to 65 0 C.
  • the ingredients of Phase B were combined; the mixture was heated to 65- 7O 0 C under stirring until dissolution of solids.
  • Phase B was added to Phase A.
  • the mixture was homogenized and added to Phase C at 55-6O 0 C.
  • the homogenized mixture was left to cool to 40-45 0 C.
  • Phase D was added, the mixture was stirred in a propeller mixer until uniform. pH was adjusted to 6.5- 7.0 using triethanolamine.
  • Composition Example 6 Sunscreen lotion (oil/water)
  • Phase B was prepared by dispersing Carbopol in water. The dispersion was heated to 70-75 0 C. The ingredients of Phase A were combined. The mixture was stirred and heated to 70-75 0 C. Phase B was added to Phase A under stirring. Phase C was added. The mixture was homogenized until it was cooled at 45-4O 0 C. Phase D was added. The mixture was stirred and left to cool to room temperature.
  • Composition Example 7 Sunscreen lotion (oil/water) with Avobenzone
  • Phase B was prepared by dispersing Carbopol in water. The dispersion was heated to 70-75 0 C. The ingredients of Phase A were combined. The mixture was stirred and heated to 70-75 0 C. Phase B was added to Phase A under stirring. Phase C was added. The mixture was homogenized until it was cooled at 45-4O 0 C. Phase D was added. The mixture was stirred and left to cool to room temperature.
  • composition Example 8 Sunscreen lipstick
  • Active ingredient 1 8.00%
  • Active ingredient 2 6.00%
  • composition Example 10 Sunscreen cream
  • Active ingredient 1 7.00%
  • Active ingredient 2 7.00%
  • composition Example 11 Water-resistance sunscreen cream
  • Active ingredient 1 8.00%
  • Active ingredient 2 7.00%
  • Active ingredient 1 4.50%
  • Composition Example 13 Sunscreen makeup powder
  • composition Example 14 Sunscreen nail-varnish

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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Abstract

Cette invention concerne des composés 3-dialkylaminophényl 2-alcoxycarbonylbenzoïque de formule (I), R étant choisi parmi l'hydrogène, alkyle en (C1-C12) linéaire ou ramifié et cycloalkyle en (C5- C7) ; R1 et R2 sont indépendamment choisis parmi hydrogène et alkyle en (C1-C6) linéaire ou ramifié, ou R1-R2 forment un groupe (CH2)n où n vaut entre 4 et 6 ; et R3-R9 sont indépendamment choisis parmi hydrogène, alkyle en (C1- C4) linéaire ou ramifié et alcoxy en (C1-C4) linéaire ou ramifié ; à condition que lorsque R1-R6 et R8-R9 sont chacun hydrogène et R7 est méthyle, R ne peut pas simultanément être hydrogène ; ou leur sel topiquement acceptable. Les composés peuvent être utilisés comme écrans solaires progressifs.
PCT/EP2010/055697 2009-04-28 2010-04-28 Composés 3-dialkylaminophényl 2-alcoxycarbonylbenzoïque Ceased WO2010125092A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP200901109 2009-04-28
ES200901109 2009-04-28

Publications (1)

Publication Number Publication Date
WO2010125092A1 true WO2010125092A1 (fr) 2010-11-04

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WO (1) WO2010125092A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111499529A (zh) * 2020-06-08 2020-08-07 湖北师范大学 一种紫外线吸收剂UVA Plus的合成方法
CN115010615A (zh) * 2022-07-14 2022-09-06 四川沃肯精细化工有限公司 一种二乙氨基羟苯甲酰基苯甲酸正己酯的制备方法
KR102633630B1 (ko) * 2023-05-22 2024-02-05 주식회사 디제이씨 n-헥실-2-(4-N,N-디에틸아미노-2-하이드록시벤조일)벤조에이트의 제조 방법
KR20250129996A (ko) 2024-02-23 2025-09-01 주식회사 젠퓨어 신규한 중간체로부터의 디에칠아미노하이드록시벤조일헥실벤조에이트 제조 방법

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1046391A2 (fr) * 1999-04-20 2000-10-25 Basf Aktiengesellschaft Usage d'hydroxybenzophénones aminosubstituées comme filtres UV photostables dans des préparations cosmétiques et pharmaceutiques

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
EP1046391A2 (fr) * 1999-04-20 2000-10-25 Basf Aktiengesellschaft Usage d'hydroxybenzophénones aminosubstituées comme filtres UV photostables dans des préparations cosmétiques et pharmaceutiques

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"The Final Over-the-Counter Drug Products Monograph on Sunscreens", FEDERAL REGISTER, vol. 64, 1999, pages 27666 - 27963
WEBER I R ET AL: "Diarylsulfonamides as selective, non-peptidic thrombin inhibitors", 7 July 1998, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, ELSEVIER SCIENCE, GB LNKD- DOI:10.1016/S0960-894X(98)00269-8, PAGE(S) 1613 - 1618, ISSN: 0960-894X, XP004137094 *
WEBER, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 8, no. 13, 1998, pages 1613 - 1618

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111499529A (zh) * 2020-06-08 2020-08-07 湖北师范大学 一种紫外线吸收剂UVA Plus的合成方法
CN115010615A (zh) * 2022-07-14 2022-09-06 四川沃肯精细化工有限公司 一种二乙氨基羟苯甲酰基苯甲酸正己酯的制备方法
CN115010615B (zh) * 2022-07-14 2023-12-08 四川沃肯精细化工有限公司 一种二乙氨基羟苯甲酰基苯甲酸正己酯的制备方法
KR102633630B1 (ko) * 2023-05-22 2024-02-05 주식회사 디제이씨 n-헥실-2-(4-N,N-디에틸아미노-2-하이드록시벤조일)벤조에이트의 제조 방법
KR20250129996A (ko) 2024-02-23 2025-09-01 주식회사 젠퓨어 신규한 중간체로부터의 디에칠아미노하이드록시벤조일헥실벤조에이트 제조 방법

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