Classifications

• • 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
• • 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
• • 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
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/35—Ketones, e.g. benzophenone
• • 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
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
  • C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/52—Stabilizers

Definitions

• the present invention relates to compounds having good capacities for absorbing ultraviolet radiation, acquiring a part of this capacity under light excitation, and whose absorption properties are photostable. It also relates to their use in cosmetic preparations as a UVA filter, and cosmetic and / or dermatological compositions containing such compounds.
• UV ultraviolet
• visible and infrared The sun emits a set of light rays that reach the earth's surface: ultraviolet, visible and infrared.
• a radiation is characterized by its wavelength and its energy, these two quantities being inversely proportional. Thus a short wavelength is associated with high energy.
• ultraviolet rays are the part of the solar spectrum concerned. These radiations, as a whole, do not exceed 5% of the total energy received on the earth's surface, but their impact on living organisms is very important. The best known of these is “sunburn” and the most sought after is “tanning”.
• Ultraviolet rays are divided into three main areas: UVA, UVB, UVC. UVCs are radiations with a wavelength between 1 90 and 290 nm.
• UVB rays with a wavelength between 290 and 320 nm, represent 2% of UV rays reaching the earth's surface. They partially penetrate the skin, and only 10 to 20% reach the dermis. They are traditionally held responsible for solar erythema but also cause greater damage, particularly at the genomic level. They are therefore attributed carcinogenic properties. UVA represents 98% of UV rays received on the surface of the
• UVA rays penetrate deeper into the skin than UVB rays. Thus 20 to 30% reach the middle dermis. They induce the formation of pigments and are responsible for tanning. In the long term, they have long been attributed a participation in accelerated skin aging, but it is only in the last ten years that we have recognized their carcinogenic potential. It should also be noted that the first generations of sunscreens did not contain UVA filters but only UVB filters. The introduction of UVA filtration has become imperative after the publication of scientific articles showing the capacity of UVA to induce skin cancers in animals (fish and mice).
• UVA photoprotection is only 100 times less effective than UVB in inducing BCC and SCC cancer in mice.
• UVA photoprotection There, for the past ten years, particular attention has been paid to UVA photoprotection.
• One of the most used is, without question, Parsol 1 789 or 4-tertiobutyl-4'- methoxydibenzoylmethane [CAS: 70356-09-1]. This molecule has a high coefficient of molar extinction in UVA with maximum absorption efficiency around 340 nm.
• his photostability is a subject of controversy.
• the first already widely used, consists in adding a molecule to the preparation, making it possible to stabilize Parsol 1,789 by various mechanisms not always explained (by way of example, various patents may be cited: FR 2,768 730 A 1, FR 2 747 038 A 1, FR 2 750 335 A1, WO 02 / 49598A2, US 6,444, 1 95 B1 ).
• the second approach much less explored, is that of the chemical modification of the molecule itself. This modification should allow the molecule to retain its UV absorption properties but to limit its propensity for photodegradation.
• the present invention thus relates to new derivatives of dibenzoylmethane, having good capacities for absorbing UV radiation, these capacities being photostable and partly photoactivable, that is to say of which the absorbing power appears in its entirety only when said dibenzoylmethane derivatives are subjected to UV exposure.
• the present invention relates to compounds derived from dibenzoylmethane of formula I,
• R R'i, R 2 ⁇ R ' 2 / R 3 , R' 3, R 4 , R ' 4, identical or different each represent: - a hydrogen atom, - or an alkyl group , linear or branched, comprising from 1 to 4 carbon atoms, - or an alkenyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an alkynyl group, linear or branched, comprising from 1 to 4 atoms of carbon, - or a C1 to C4 alkoxy group, - or a halogen atom, - or a hydroxy group, - or an amino group, - or a nitro group, - or an amido group, - or a carbonyl group of formula -CO-Y, in which Y represents the group -OH, -OR or -SR (R representing a C1 to C4 alkyl), a halogen atom.
• R 5 and R ' 5 different ⁇ each represent: - a hydrogen atom, - or an alkyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an alkenyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an alkynyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising from 5 to 20 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, functionalized at its end, comprising from 5 to 20 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising a nitrogen atom of amine or amide function and / or an oxygen atom of ether or carboxylic function. comprising from 5 to 20 carbon atoms, as well as their salts or solvates.
• R RN R 2 , R ' 2 ⁇ R 3 , R' 3, R 4 , and R ' 4 each represent a hydrogen atom.
• R 5 and R ' 5 different each represent: - a hydrogen atom, - or an alkyl group, linear or branched, comprising from 1 to 4 atoms of carbon, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising from 5 to 20 carbon atoms
• R v R ' v R 2 , R' 2 / R 3 , R ' 3 ⁇ R 4 , and R' 4 each represent a hydrogen atom.
• R 5 and R ' 5 different each represent: - a hydrogen atom - or an alkyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising from 5 to 20 carbon atoms
• R 5 and R ' 5 identical or different, each represent: - an alkyl group, linear or branched, comprising from 1 to 4 carbon atoms, or an alkenyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an alkynyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising from 5 to 20 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, functionalized at its end, comprising from 5 to 20 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising a nitrogen atom of amine or amide function and / or an ether or carboxylic oxygen atom.
• R RN R 2 , R ' 2 , R 3 .- R' 3, R and R ' 4 each represent a hydrogen atom.
• R 5 and R ' 5 identical or different , each represent: - an alkyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising from 5 to 20 carbon atoms
• R 5 and R ' 5 identical or different each represent: - an alkyl group, linear or branched, comprising from 1 to 4 carbon atoms, - or an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising from 5 to 20 carbon atoms
• these dibenzoylmethane derivatives can be obtained from a dibenzoylmethane, optionally substituted, by an alkylation reaction according to a protocol similar to those described by MARZINZIK and FELDER (Tetrahedron Letters, Vol. 37, No. 7, pp 1003-1006, 1996) and CLARK and MILLER (JCS Perkin I, pp 1743-1745, 1977).
• the alkylammonium halide used is either a fluoride, or a chloride, or a bromide, or an alkylammonium iodide, preferably tetrabutylammonium fluoride.
• This tetrabutylammonium halide is present either in aqueous solution or in solution in tetrahydrofuran (THF). Therefore, the preparation of the dibenzoylmethane / tetrabutylammonium halide complex is carried out either in an aqueous medium or in an organic medium, preferably in THF.
• the actual alkylation is carried out in an organic solvent such as tetrahydrofuran (THF), acetonitrile, chloroform, preferably THF.
• THF tetrahydrofuran
• the reaction medium is kept under stirring at room temperature or at reflux, preferably at reflux for 2 to 24 hours, preferably 8 hours.
• the alkylating agent can be an alkane halide such as a fluoroalkane, a chloroalkane, a bromoalkane, an iodoalkane, preferably bromoalkane, having from 1 to 20 carbon atoms, preferably 10.
• the starting dibenzoylmethane derivatives, optionally substituted, that is to say the compounds of formula (I), in which R5 and R'5 each represent a hydrogen can be prepared by known synthetic methods such as Claisen condensation (see Organic Reactions, volume VIII, John Wiley and Sons, 1,954), that is to say the condensation between a compound of general formula AR-X and AR'-Y, in which AR and AR 'identical or different each represent a phenyl group optionally mono or polysubstituted, and X and Y, different each represent a methoxycarbonyl group and an acetyl group.
• This condensation reaction is advantageously carried out in the presence of a strong base, in the presence of an inert solvent.
• the invention also relates also to the process for the preparation of a compound of formula (I) as defined above, characterized in that it comprises: a step of forming a complex in aqueous or organic medium, between a) a molecule of general formula (I) in which R ,, RN R 2 , R ' 2 R 3 , R' 3 R 4 , and R ' 4 each represent a group defined in any one of Claims 1 to 4, and R 5 and R ' 5 , identical each represent a hydrogen atom, and b) an alkylammonium halide, then - a step of substitution of at least one of the hydrogens represented by R 5 or R' 5 , in an organic medium with action of at least one halide of general formula R 5 X or R ' 5 X, in which R 5 and R' 5 , which are identical or different, each represent a group defined above.
• R 5 or R ' 5 is an alkylation by the action of at least one alkylating agent of general formula R 5 X or R ' 5 X, in which R 5 and R' g, which are identical or different, each represent an acyclic carbon chain, linear or branched, saturated or unsaturated, comprising from 1 to 20 carbon atoms
• the dibenzoylmethane derivatives thus obtained have a conjugate system analogous to the reference compound described above, namely Parsol 1789 or 4-tertbutyl, -4'- methoxydibenzoylmethane, they therefore exhibit absorption capacities in the ultraviolet As a 'illustration of these absorption capacities in the ultraviolet, measurements were carried out for two dibenzoylmethane derivatives according to the invention.
• Compound 010 has a strong solvochromy which brings the maximum absorption in the UVA to around 360 nm for organized solvents (for example micellar solutions of sodium dodecyl sulfate). The same is true for compound C10.
• these two compounds subjected to ultraviolet radiation, see their wavelength of maximum absorbance pass from UVB to UVA, thus causing the same effect as the organization of the system. So that the maximum displacement of the absorption bands towards UVA is obtained by placing these compounds in an organized medium under irradiation, as is the case for a sunscreen cosmetic preparation under the normal conditions of its use. The irradiation of the preparation amplifies the phenomenon induced by the medium in which the compounds are found.
• the dibenzoylmethane derivatives according to the invention can thus advantageously be used in cosmetic and or dermatological preparations as sunscreens.
• the present invention therefore also relates to a cosmetic and / or dermatological composition characterized in that it comprises as active ingredient at least, a compound of formula (I), according to claims 1 to 4 or one of its salts or solvates , as defined above. It also relates to a composition as previously defined, characterized in that it also comprises another active principle.
• composition as defined above, characterized in that the other active principle is a filter chosen from the group consisting of PARSOL 1,789, 2,4,6-tris [p- (2'-ethylhexyl -1 '-oxycarbonyl) anilino] -1, 3,5-triazine, 4- (t-butyl) -4'- methoxy-dibenzoylmethane, 2-hydroxy-4-methoxy-benzophenone, and 3- (4'-methylbenzylidene) -camphor.
• the other active principle is a filter chosen from the group consisting of PARSOL 1,789, 2,4,6-tris [p- (2'-ethylhexyl -1 '-oxycarbonyl) anilino] -1, 3,5-triazine, 4- (t-butyl) -4'- methoxy-dibenzoylmethane, 2-hydroxy-4-methoxy-benzophenone, and 3- (4'-methylbenzylidene) -
• composition according to the invention characterized in that it contains from 0.5 to 30% by weight relative to the total weight of the composition, preferably from 1 to 10%, of said active principle.
• compositions according to the invention may also contain conventional cosmetic adjuvants in particular chosen from fatty substances, organic solvents, ionic or nonionic thickeners, softeners, antioxidants, opacifiers, stabilizers, emollients, silicones, defoamers, moisturizers, vitamins, fragrances, preservatives, surfactants, fillers, inorganic or organic pigments, sequestrants, polymers, propellants, alkalizing or acidifying agents, colorants, or any other ingredient usually used in cosmetics, in particular for the manufacture of sunscreen compositions in the form of emulsions. They can also contain one or more complementary sunscreens active in UVA and / or UVB, hydrophilic or lipophilic.
• the present invention also relates to the use of a compound of formula (I) according to the invention or one of its salts or solvates, as an agent for protecting the skin or the hair against UV radiation.
• the invention also relates to a cosmetic and / or dermatological product characterized in that it comprises, as active principle, a compound of formula (I) according to the invention or one of its salts or solvates.
• Example 1 1 - (4-methoxyphenyl) -3- (4-tertbutylphenyl) -propane-1, 3-dione
• reaction medium is maintained at ambient temperature, with magnetic stirring for 26 hours.
• a viscous orange residue is obtained after filtration and evaporation of the solvent.
• a succession of open columns are then produced in order to remove the excess of reagents ( alkylating agent, C 10 H 21 Br and TBAF) and separate the three molecules present in the medium: the unreacted starting molecule, the molecule having for R 5 the acyclic carbon chain, linear saturated, comprising 10 carbon atoms and an H for HR 'R 2 , R' 2 R 3 , R ' 3 R 4 , R' 4 , R ' 5 , and the molecule having for R' 5 the acyclic carbon chain, linear saturated, comprising 10 carbon atoms and an H for R.
• reagents alkylating agent, C 10 H 21 Br and TBAF
• reaction medium is maintained at reflux, with magnetic stirring for 8 hours.
• a viscous orange residue is obtained after filtration and evaporation of the solvent.
• a succession of open columns are then produced in order to remove the excess of reagents (alkylating agent C 10 H 21 Br and TBAF) and to separate the three molecules present in the medium: the unreacted starting molecule, the molecule having for R 5 the acyclic carbon chain, linear saturated, comprising 10 carbon atoms and an H for R 1 f R ',, R 2 , R' 2 / R 3 , R ' 3, R 4 , R' 4 and R ' 5 , and the molecule having for R' 5 the acyclic carbon chain, linear saturated, comprising 10 atoms carbon and an H for R ,, RN R 2 , R ' 2 ⁇ R 3 , R' 3, R 4 , R ' 4 , and R 5.
• the open columns are made in the same way way as before. Separation in HPLC; column C1 8;
• Parsol 1 789 gives 2.59 g of compound C10 and 2.47 g of compound 010, ie respective yields of 34 and 36%.
• the NMR spectra were performed with a Bruker ARX 400 MHz device.
• the UV absorption spectra were performed on an HP 8452 A Diode Array Spectrometer.
• the infrared spectra were performed on a Perkin-Elmer 1,760 X device.
• Stability tests against UV radiation For example, changes under irradiation of a basic preparation (water in oil emulsion) containing the compounds obtained in the previous examples, namely compound C10 and compound 010, are compared to that of the same preparation containing Parsol 1,789 (% by mass equivalent for each filter).
• the preparations chosen may be composed as follows: Glycasil L 0.19%, butylparaben 0.3%, beeswax 4%, PEG-30 dipolyhydroxystearate 3%, dicapryl carbonate 10%, polyglyceryl-3- diisostearate 1 .5%, water 78.64%, xanthan gum 1%, Na 2 EDTA 0.2%, NaCl 1%; methylparaben 0.17%
• the compounds C10 or O10 or Parsol 1789 in% by mass equivalent may be composed as follows: Glycasil L 0.19%, butylparaben 0.
• the two compounds tested therefore exhibit better photostability than Parsol 1 789.
• their molar extinction coefficient is lower than that of Parsol 1 789 by about 30% (when the maximum absorption is reached by irradiation). It may thus be possible to use the dibenzoylmethane derivatives according to the invention in combination with other filters such as Parsol 1 789, the dibenzoylmethane derivatives according to the invention protecting Parsol 1 789 by screen effect. This association makes it possible to use a minimum mass of filter for a maximum filtering effect.
• a preparation similar to the previous ones containing 1% by mass of filters in total, including 32.5% of Parsol 1,789, 35% of compound C10 and 32.5% of compound O10 (molar%) was irradiated with sun under the same conditions as above and its evolution was compared to that of a preparation containing 1% by mass of Parsol 1 789.
• the mixed preparation retains its initial absorbance (or greater absorbance) in UVA for 1 h and that- this decreases by 33% after 2 hours.
• the preparation containing only Parsol 1 789 sees its absorbance decrease regularly from the start of the exposure. This decrease reaches 51% in 1 hour and 73% in 2 hours.
• a preparation similar to the previous ones containing 1% by mass of filters in total, including 10% of Parsol 1789, 30% of compound C10 and 60% of compound O 1 0 (molar%) was irradiated in the sun in the same conditions as above and its development was compared to that of a preparation containing 1% by mass of Parsol 1,789.
• the mixed preparation retains its initial absorbance (or greater absorbance) in UVA for 2 h 30 min.

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• 2003
  • 2003-07-17 FR FR0308736A patent/FR2857663B1/fr not_active Expired - Lifetime
• 2004
  • 2004-07-15 US US10/564,888 patent/US7446230B2/en not_active Expired - Fee Related
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