EP1059912A2 - Verwendung von calcium- oder natrium-kanal-blockern enthaltende zusammensetzung zur topische anwendung - Google Patents

Verwendung von calcium- oder natrium-kanal-blockern enthaltende zusammensetzung zur topische anwendung

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Publication number
EP1059912A2
EP1059912A2 EP99937868A EP99937868A EP1059912A2 EP 1059912 A2 EP1059912 A2 EP 1059912A2 EP 99937868 A EP99937868 A EP 99937868A EP 99937868 A EP99937868 A EP 99937868A EP 1059912 A2 EP1059912 A2 EP 1059912A2
Authority
EP
European Patent Office
Prior art keywords
composition
skin
composition according
inhibitor
activity
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP99937868A
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English (en)
French (fr)
Inventor
Isabelle Nonotte
Lionel Breton
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LOreal SA
Original Assignee
LOreal SA
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Filing date
Publication date
Application filed by LOreal SA filed Critical LOreal SA
Publication of EP1059912A2 publication Critical patent/EP1059912A2/de
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • 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
    • A61K8/37—Esters of carboxylic acids
    • 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
    • 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
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • 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
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive skin
    • 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
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/75—Anti-irritant

Definitions

  • the present invention relates to the use of at least one compound partially or totally inhibiting the activity of a sodium channel or of a calcium channel, with the exception of lanthanum and lanthanides, in a cosmetic composition and / or pharmaceutical, to increase the tolerance threshold of the skin, particularly sensitive skin or intolerant skin, and more especially to suppress itching, pruritus, tightness, tingling and / or erythema.
  • the cell membranes of each nerve fiber or of certain skin cells comprise numerous ion channels, and in particular sodium or calcium channels.
  • the role of these different channels is to allow sodium or calcium ions to pass on either side of the cell membrane.
  • the Applicant has found that the sensitive nerve fibers present in the skin as well as certain cutaneous cells such as keratinocytes and melanocytes, contain sodium or calcium channels. On the other hand, the Applicant has also found that there is a link between the activity of these channels and the threshold of excitability of the skin, particularly in sensitive skin or in intolerant skin. She therefore found that one could act on these channels to increase the tolerance threshold of a skin.
  • inhibitor compounds The substances that inhibit these channels, and which therefore decrease the entry of sodium or calcium ions into cells, are called inhibitor compounds.
  • the present invention relates to the use of at least one compound partially or totally inhibiting the activity of at least one sodium channel or of a calcium channel, with the exception of lanthanum and lanthanides, in and / or for the preparation of a composition for increasing the tolerance threshold of the skin.
  • tolerance threshold of the skin is meant the threshold of excitability of the skin beyond which the skin responds to an external aggression by signs such as dysesthetic sensations, that is to say more or less painful sensations felt in a skin area such as tingling, tingling, itching or pruritus, burning, sensations of heating, discomfort, tightness and / or redness or erythema etc.
  • irritant products such as surfactants, preservatives or perfumes, as the environment, emotions, food, wind, friction, razor, soap, surfactants, hard water with a high concentration of limestone, temperature variations or wool, etc.
  • a subject of the invention is also the use of at least one compound partially or totally inhibiting the activity of at least one sodium channel or of one calcium channel, with the exception of lanthanum and lanthanides, in and / or for the manufacture of a composition for topical use to prevent, treat, or even suppress, tingling, tingling, itching or pruritus, burns, sensations of heating, discomfort, tightness and / or redness and / or erythema.
  • the invention also relates to the use of at least one compound partially or totally inhibiting the activity of at least one sodium channel or of a calcium channel of at least one cutaneous sensory nerve fiber and / or of at least one keratinocyte and / or at least one melanocyte, with the exception of lanthanum and lanthanides, in and / or for the manufacture of a composition for topical use to increase the tolerance threshold of the skin.
  • the invention also relates to the use of at least one compound partially or totally inhibiting the activity of at least one sodium channel or of a calcium channel of at least one cutaneous sensory nerve fiber and / or of at least one keratinocyte and / or at least one melanocyte, with the exception of lanthanum and lanthanides, in and / or for the manufacture of a composition for topical use for preventing, treating, or even eliminating stinging, tingling, itching or pruritus, burning, overheating, discomfort, tightness and / or redness and / or erythema.
  • the subject of the invention is also a method of cosmetic treatment of the skin, comprising the topical application to the skin of a topical cosmetic composition containing at least one compound partially or totally inhibiting the activity of at least one sodium channel or a calcium channel, with the exception of lanthanum and lanthanides, present or not in the cutaneous tissue, to increase the tolerance threshold of the skin or to prevent, treat, or even suppress, tingling, tingling, itching or pruritus, burns, sensations of heating, discomfort, tightness and / or redness and / or erythema, whether or not the canal is associated with a sensitive skin nerve fiber and / or at least one keratinocyte and / or at least one melanocyte.
  • partially or even completely preventing the entry of sodium or calcium into the cell amounts to increasing the threshold of excitability or tolerance of sensitive skin or intolerant skin.
  • the subject of the invention is the use of at least one compound partially or totally inhibiting the activity of at least one sodium channel or of a calcium channel, with the exception of lanthanum and lanthanides, in and / or for the preparation of a composition for increasing the tolerance threshold of sensitive skin or intolerant skin or for preventing, treating, or even eliminating, tingling, tingling, itching or pruritus, burns , overheating sensations, discomfort, tightness, redness and / or erythema, whether or not the channel is a sodium or calcium channel of at least one sensitive skin nerve fiber and / or at least one keratinocyte and / or at least one melanocyte.
  • the subject of the invention is a method of cosmetic treatment of sensitive skin or intolerant skin comprising the topical application to said skin of a cosmetic topical composition containing at least one compound partially or totally inhibiting the activity of at least one sodium channel or one calcium channel, with the exception of lanthanum and lanthanides, for increasing the tolerance threshold of sensitive skin or for intolerant skin or for preventing, treating, or even eliminating , tingling, tingling, itching or itching, burning, overheating, discomfort, tightness and / or redness and / or erythema, whether or not the sodium channel or a calcium channel of at least one cutaneous sensory nerve fiber and / or at least one keratinocyte and / or at least one melanocyte.
  • an inhibitor which is both an inhibitor of at least one calcium channel and at least one sodium channel or also to use the calcium and sodium channel inhibitors alone or mixed.
  • sodium or calcium channels mention may be made of the calcium voltage dependent channels of type L, T, N, P, Q and R as described in the journal “Pharmacological Review”, (1992, vol. 44, 3, 363-375 ) as well as the sodium channels described in the review “International Revue of Cytology”, (1993, vol. 137c, 55-103) or in the review “Annu. Rev. Biophys. Chem.”, (1991, tome 20, 65 -78) or in the review "J. Gen. Physiol.”, (1993, vol.101, 153-182).
  • one of the sodium channels can be the ASIC (Acid-Sensing lonic Chanel) channel described by M. Lazdunski et al. in Nature, vol. 386, pp. 173-177, March 1997.
  • ASIC Acid-Sensing lonic Chanel
  • the invention can be used as cation channel inhibitors: Nicardipine, Nitrendipine, Nifedipine, Nimodipine, Niguldipine, Amiloride, Pimozide, Quinidine, Quinidine sulfate, Rouge de Ruthenium, Verapamil, N-acetylprocainamide, Apamine, Cyproheptadine, Diltiazem, Loperamide.
  • Verapamil and / or Amiloride are used.
  • the amount of inhibitor of at least one sodium channel or at least one calcium channel used according to the invention is of course a function of the desired effect and can therefore vary to a large extent.
  • the inhibitor can be in an amount representing from 0.0001% to 10% of the total weight of the composition and preferably in an amount representing from 0.001% to 5% of the total weight of the composition.
  • At least one inhibitor of at least one sodium channel or at least one calcium channel can be combined with products having an irritant effect commonly used in the cosmetic or pharmaceutical field, products which are sometimes cosmetic or pharmaceutical active ingredients.
  • products having an irritant effect commonly used in the cosmetic or pharmaceutical field products which are sometimes cosmetic or pharmaceutical active ingredients.
  • the presence of an inhibitor of a sodium channel or a calcium channel in such a composition, whether cosmetic or pharmaceutical, comprising a product having an irritant effect makes it possible to greatly attenuate, or even to eliminate this irritant effect.
  • the invention relates more particularly to a cosmetic or pharmaceutical composition, characterized in that it comprises, in a medium cosmetically or pharmaceutically acceptable, at least one inhibitor of at least one sodium channel or at least one calcium channel and at least one product with an irritant effect.
  • surfactants ionic or non-ionic
  • preservatives organic solvents or active agents such as ⁇ -hydroxy acids (citric, malic, glycolic, tartaric, mandelic, lactic acid).
  • ⁇ -hydroxy acids salicylic acid and its derivatives
  • ⁇ -keto acids ⁇ -keto acids
  • retinoids retinol, retinal, retinoic acid
  • anthralins dioxyanthranol
  • anthranoids peroxides (especially benzoyl)
  • minoxidil lithium salts, antimetabolites, vitamin D and its derivatives, hair dyes or dyes (paraphenylenediamine and its derivatives, aminophenols)
  • perfume alcoholic solutions perfumes, toilet waters, after shaving, deodorants
  • antiperspirants certain aluminum salts
  • depilatory or perming active ingredients thiols
  • depigmenting active ingredients hydroquinone
  • the inhibitor of a sodium channel or of a calcium channel is an inhibitor as described previously in the text.
  • the whole mechanism is also under the control of the sensitive nerve endings which release neuropeptides, in particular substance P and CGRP.
  • the subject of the present invention is a cosmetic or pharmaceutical composition, characterized in that it comprises, in a cosmetically or pharmaceutically acceptable medium, at least one inhibitor of a sodium channel or of a calcium channel and at least one compound which decreases the synthesis, release and / or activity of at least one inflammation mediator.
  • cosmetically acceptable medium means a medium compatible with the skin, the mucous membranes, the nails and the hair.
  • the composition according to the invention comprises at least one compound decreasing the synthesis, the release and / or the activity of at least one mediator of cutaneous inflammation in association with an inhibitor of a sodium channel or of a calcium channel.
  • the inhibitor of a sodium channel or of a calcium channel is an inhibitor as described previously in the text.
  • the compound which decreases the synthesis, release and / or activity of at least one inflammation mediator is preferably chosen from steroidal or non-steroidal anti-inflammatory drugs, substance P and / or CGRP antagonists, inhibitors of NO synthase, bradykinin antagonists, cytokine antagonists, histamine antagonists, tumor necrosis factor ⁇ type (TNF ⁇ ) antagonists.
  • an antagonist when used, it is a receptive antagonist.
  • steroidal anti-inflammatory agents examples include hydrocortisone, betamethasone valerate or clobetasol propionate.
  • non-steroidal anti-inflammatory agents is meant here the anti-inflammatory agents as described by Schorderet and Dayer in Pharmacology, "From fundamental concepts to therapeutic applications", 1992, chapter 37, pages 541-561, 2nd edition, Frison-Roche / Slatkine editors.
  • arylcarboxylic acids such as salicylic acid derivatives or anthranilic acid derivatives
  • arylalkanoic acids such as acids arylacetic and hetero-arylacetic or arylpropionic acids
  • enolic acids such as pyrazolone derivatives or oxicams
  • non-acidic derivatives such as, for example, bufexamac (Merck Index, 11th edition (MI) 1462), benzydamine ( Ml 1136), epirizole (Ml 3572), fiuproquazone (Ml 4120) or tiaramide (Ml 9356).
  • the substance P antagonist is chosen from the substances ensuring a reduction in the extravasation of the plasma through the vascular wall induced by capsaicin or by antidromic nerve stimulation and the substances causing an inhibition of the contraction of the smooth muscles induced by administration of substance P.
  • the substance P antagonist is chosen from peptides, non-peptide compounds such as those comprising at least one heterocycle, nitrogen compounds comprising at least one benzene ring, monovalent, divalent and trivalent cation salts, thermal waters, extracts plants or microorganisms, and mixtures thereof.
  • the sendide corresponds to the formula:
  • Tyr represents tyrosine
  • D-Phe represents D-phenylalanine
  • Phe represents phenylalanine
  • D-His represents D-histidine
  • Leu represents leucine
  • Met represents methionine.
  • Spantide II corresponds to the formula:
  • D-NicLys represents D-lysine nicotinate
  • Pro represents praline
  • 3-Pal represents 3-pyridyl-alanine
  • D-Cl2Phe represents D-dichlorophenylalanine
  • D-Trp represents D-tryptophan
  • Phe represents phenylalanine
  • Leu represents leucine
  • substance P antagonist peptide As substance P antagonist peptide, the peptides described in documents US-A-4472305, US-A-4839465, EP-A-101929, EP-A-333174, EP-A- 336230, EP-A-394989,
  • EP-A-443132 EP-A-498069, EP-A-515681, EP-A-517589, WO-A-92/22569 and
  • non-peptide substance P antagonists which can be used in the invention are in particular compounds comprising a heteroatom linked directly or indirectly to a benzene ring or contained in a heterocycle.
  • this heteroatom is an oxygen, nitrogen or sulfur atom.
  • heterocyclic compound it is possible in particular to use in the invention those described in the following documents: EP-A-360390, EP-A-429366, EP-A-430771, EP-A-499313, EP-A-514273, EP -A-514274, EP-A-514275, EP-A- 514276, EP-A-520555, EP-A-528495, EP-A-532456, EP-A-545478, EP-A-558156, WO-A -90/05525, WO-A-90/05729, WO-A-91/18878, WO-A-91/18899, WO-A-92/12151, WO-A-92/15585, WO-A-92 / 17449, WO-A-92/20676, WO-A-93/00330, WO-A-93/00331, WO-A-93/01159, WO-A-93/01169, WO-A-93/01170
  • the compound comprising at least one nitrogen heterocycle is a 2-tricyclyl-2-amino-ethane derivative, a spirolactam derivative, a quinuclidine derivative, an azacyclic derivative, an aminopyrrolidine derivative, a piperidine derivative, an aminoazaheterocycle or an isoindole derivative.
  • heterocyclic compounds such as furan derivatives, benzofuran derivatives, thiophene derivatives and benzothiophene derivatives, optionally comprising nitrogen substituents, such as the heterocyclic compounds described in documents US-A-4931459, US- A-4910317 and EP-A-299457, and more especially the alkoxy- and or aryloxy-tetrazolyl-benzofuran-carboxamides or the alkoxy- and / or aryloxy-tetrazolyl-benzothiophene-carboxamides.
  • oxygenated or sulfur-containing heterocyclic compounds such as furan derivatives, benzofuran derivatives, thiophene derivatives and benzothiophene derivatives, optionally comprising nitrogen substituents, such as the heterocyclic compounds described in documents US-A-4931459, US- A-4910317 and EP-A-299457, and more especially the alkoxy- and or aryloxy-tetrazolyl-benzofur
  • the cation salts which can be used. in the invention are in particular the salts of strontium, magnesium, lanthanides with atomic number ranging from 57 to 71, cobalt, nickel, manganese, barium, yttrium, copper, tin, rubidium , lithium and zinc.
  • salts can be for example carbonates, salicylates, bicarbonates, sulfates, glycerophosphates, borates, chlorides, nitrates, acetates, hydroxides, persulfates as well as ⁇ -hydroxyacid salts (citrates, tartrates, lactates, malates) or fruit acids, or even amino acid salts (aspartate, arginate, glycocholate, fumarate) or fatty acid salts (palmitate, oleate, caseinate, behenate).
  • the salt is chosen from strontium, manganese, yttrium or magnesium nitrate, strontium, manganese, yttrium or magnesium borate, strontium, manganese or magnesium chloride, magnesium, manganese or strontium sulfate. Even more preferably, these salts are strontium chloride or nitrate.
  • water from the Lucas spring is used.
  • substance P antagonist an extract prepared from plant material such as for example an extract of Iridaceae.
  • Iridaceae extract can be any extract prepared from plant material from the Iridaceae family.
  • Iridacea extract can be obtained from plant material from plants whole grown in vivo or from in vitro culture.
  • the extract may be an organ extract or even organ cells of at least one Iridaceae (roots, stem, leaf) or else an extract of undifferentiated cells of at least one Iridaceae. .
  • an extract obtained from undifferentiated cells obtained by culture in vivo or in vitro is used.
  • in vitro culture means all of the techniques known to those skilled in the art which artificially make it possible to obtain a plant or part of a plant.
  • an extract obtained from plant material cultivated in vitro is used and even more preferably an extract obtained from undifferentiated cells cultivated in vitro.
  • undifferentiated plant cells any plant cell having none of the characteristics of a particular specialization and capable of living by itself and not in dependence on other cells. These undifferentiated plant cells are possibly capable, under the effect of an induction, of any differentiation in accordance with their genome. According to the chosen culture method, and in particular according to the chosen culture medium, it is possible to obtain, from the same explant, undifferentiated plant cells having different characters.
  • the Iridaceae (or Iridae) family has around 750 species. Plants of the Iridaceae family are mainly used for their aromatic and ornamental properties. Among the genera of Iridacees which can be used according to the invention, mention may be made, by way of example, of the genera Romulea, Crocus, Iris, Gladiolus, Sisyrinchium or even Hermodactylus. As plant material which can be used, mention may be made of that originating from Iris germanica, Iris florentina, Iris pallida, Crocus versicolor, Romulea bulbucodium or even Gladiolus communis.
  • plant material from the genus Iris is used and preferably plant material from Iris pallida.
  • Any extraction method known to those skilled in the art can be used to prepare the extract contained in the composition according to the invention. Mention may, in particular, be made of alcoholic extracts, especially ethanolic or even hydroalcoholic.
  • a first step the plant material is ground in a cold aqueous solution
  • the particles in suspension are removed from the aqueous solution obtained from the first step
  • a third step the aqueous solution obtained from the second step.
  • This aqueous solution corresponds to the extract.
  • the first step can advantageously be replaced by a simple freezing operation of the plant tissues (for example at -20 ° C.), followed by an aqueous extraction repeating the second and third steps described above.
  • the substance P antagonists can be used alone or as a mixture.
  • CGRP antagonist any compound capable of partially or even completely inhibiting the biological effect of CGRP.
  • a substance to be recognized as a CGRP antagonist it must induce a coherent pharmacological response (including or not its attachment to the CGRP receptor) in particular in one of the following tests
  • the antagonist substance must decrease the vasodilation induced by capsaicin and / or by antidromic electrical stimulation (applied to an afferent nerve) and / or
  • the antagonist substance must cause an inhibition of the release CGRP by sensitive nerve fibers and / or
  • the antagonist substance must cause an inhibition of the contraction of the smooth muscle of the vas deferens induced by CGRP.
  • CGRP 8-37 amino acid sequence 8 to 37 of the N-terminal part of CGRP
  • anti-CGRP antibodies antibodies
  • non-photosynthetic filamentous bacteria extract is understood to mean both the culture supernatant of said bacteria, the biomass obtained after culture of said bacteria or else the extracts of biomass obtained by treatment of this biomass.
  • the extracts of bacteria according to the invention are prepared from non-photosynthetic filamentous bacteria as defined according to the classification of Bergey's Manual of Systematic Bacteriology (vol. 3, sections 22 and 23, 9th edition, 1989), among which one can cite the bacteria belonging to the Beggiatoales order, and more particularly the bacteria belonging to the genera Beggiatoa, Vitreoscilla, Flexithrix or Leucothrix.
  • the bacteria which have just been defined and several of which have already been described generally have an aquatic habitat and can be found in particular in marine waters or in thermal waters.
  • the bacteria that can be used there may be mentioned for example:
  • Vitreoscilla filiformis (ATCC 15551) Vitreoscilla beggiato ⁇ des (ATCC 43181)
  • a strain of Vitreoscilla filiformis is used according to the invention.
  • said bacteria can be cultivated according to methods known to those skilled in the art, then separated from the biomass obtained, for example by filtration, centrifugation, coagulation and / or lyophilization.
  • the bacteria are concentrated by centrifugation.
  • the biomass obtained is autoclaved.
  • This biomass can be lyophilized to constitute what is called the lyophilized extract. Any lyophilization method known to those skilled in the art can be used to prepare this extract.
  • the supernatant fraction of this biomass can also be filtered in a sterile container to remove suspended particles. The extract thus called elsewhere in the aqueous extract text is thus obtained.
  • the CGRP antagonists can be used alone or as a mixture.
  • the term NO-synthase in fact covers a family of enzymes which, in a specific manner, ensure the enzymatic catalysis of L-arginine into citrulline, catalysis during which a gas mediator with multiple functions is produced, nitric oxide or NO.
  • Nitric oxide has, by its structure, an additional electron making it extremely chemically reactive. It is well known that such compounds are harmful and we seek to limit their production as much as possible. Thus, in the case of nitric oxide, the NO-synthase inhibitors have been widely studied.
  • the NO-synthase inhibitors are products which make it possible, in situ on humans, to partially or even completely inhibit the synthesis of nitrogen monoxide (NO).
  • the NO synthase inhibitor can be chosen from peptides, synthetic or natural, optionally modified, chemical, synthetic or natural molecules, antisense nucleic acids, ribozymes, anti-NO synthase antibodies.
  • N G -monomethyl-L-arginine L-NMMA
  • N G -nitro-L-arginine the methyl ester of N G -nitro-L -arginine, diphenyleneiodonium chloride, 7-nitroindazole
  • N (5) - (1-iminoethyl) -L-omithine N G , N G -dimethyl-L-arginine, N G , N G -dimethyl - arginine, 2- (4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide, aminoguanidine
  • canavanine ebselen and the hormone stimulating melanocytes type ⁇ .
  • NO synthase inhibitors use is preferably made of N G -monomethyl-L-arginine and the hormone stimulating melanocytes of the ⁇ type. NO synthase inhibitors can be used alone or as a mixture.
  • Bradykinin is a peptide of plasma origin released from a kininogenic precursor by a plasma protease called Kallikreine (EC 3.4.21.24). This nanopeptide is one of the key mediators of inflammation and has mitogenic properties.
  • the receptors for this kinin fall into two main subtypes, B1 and B2. Bradykinin acts in particular on the B2 receptor and causes the stimulation of numerous production systems of second messengers including the hydrolysis of inositol-phosphates, the metabolism of arachidonic acid, the phosphorylation of tyrosine residues as well as depolarization or hyperpolarization of the cell membrane.
  • bradykinin antagonist means any compound capable of partially or even completely inhibiting the biological effect of bradykinin.
  • bradykinin antagonist for a substance to be recognized as a bradykinin antagonist, it must induce a coherent pharmacological response including or not its attachment to the bradykinin receptor.
  • this compound includes any compound which may interfere with the effects of bradykinin by its attachment to the receptor thereof (B1 or B2) and / or any compound which independently of the binding to the receptor (s) induced by any mechanism an effect contrary to that known to bradykinin (for example interfering with the synthesis of bradykinin).
  • bradykinin antagonists it is preferred to use compounds which inhibit the synthesis and / or accelerate the catabolism of bradykinin, compounds which neutralize bradykinin, compounds which block bradykinin receptors such as those which interfere with the effects of bradykinin by their attachment to the receptor thereof (B1 or B2), compounds inhibiting the synthesis of bradykinin receptors or compounds intervening by reducing the signal transduced by bradykinin.
  • These compounds can be of natural or synthetic origin.
  • bradykinin antagonists mention may be made more particularly of peptides, synthetic or natural, optionally modified, such as D-Arg, [Hyp3, D-Phe7] -bradykinin (NPC567), [Thi 5, 8, D- Phe7] -bradykinin, D-Arg, [Hyp3, Thi5.8, D-Phe7] -bradykinin, N- ⁇ -adamantaneacetyl-D-Arg, [Hyp3, Thi5.8, D-Phe7] -bradykinin des-Arg9, [Leu8] -bradykinin (all sold by the company Sigma) or the compounds cited in patents WO 95/08566, WO 95/07294, EP 0623350, EP 0622361, WO 94/11021, EP 0596406, WO 94/06453, WO 94/09001, EP 0578521, EP 0564972, EP 0552106, WO 93/
  • Bradykinin Antagonists development and applications (Stewart JM, Biopolymers, 1995, 37, 143-155), or chemical, synthetic or natural molecules, such as those described in Salvino et al. J. Med. Chem., 1993, 36, 2583-2584.
  • antisense nucleic acids or ribozymes whose purpose is to selectively inhibit the synthesis of bradykinin.
  • antisense nucleic acids are known to those skilled in the art. They can act in different ways on the DNA or on the messenger RNA coding for bradykinin, in particular by blocking the binding or the progression of ribosomes along the messenger RNA, by cleavage of the messenger RNA by the RNase H, or by preventing the transport of messenger RNA from the nucleus to the cytoplasm or by preventing the processing of messenger RNA.
  • Antibodies to bradykinin or soluble bradykinin receptors, antibodies to bradykinin receptors or bradykinin receptor antagonists can also be used according to the invention.
  • a compound which interferes with the effects of bradykinin by its attachment to the receptor for the latter (B1 or B2), preferably to the B2 receptor.
  • a bradykinin antagonist is chosen according to the invention chosen from: D-Arg, [Hyp3, D-Phe7] -bradykinin (NPC567), [Thi 5, 8, D-Phe7] -bradykinin, D-Arg, [Hyp3, Thi5.8, D-Phe7] -bradykinin, N- ⁇ -adamantaneacetyl-D-Arg, [Hyp3, Thi5.8, D-Phe7] -bradykinin, la des-Arg9, [ Leu8] -bradykinin, P-guanidobenzoyl, [Hyp3, Thi5, D-Tic7, Oic8] -bradyklnin (S 16118), D-Arg, [Hyp3, Thi5, D-Tic7, Oic8] -bradykinin (HOE 140) , D-Arg, [Hyp3, D-Hype (trans-propyl) 7, Goose 8
  • bradykinin antagonists can be used alone or as a mixture.
  • the term “histamine, cytokine and / or TNF- ⁇ antagonists” is intended to mean any substance capable of inhibiting the release and / or the synthesis and / or the receptor fixation, respectively, of histamine, cytokines and / or TNF- ⁇ .
  • Antagonists inhibiting receptor binding of histamine are specific agents of the histamine type 1 receptor (H1).
  • cytokines For a substance to be recognized as a receptor antagonist histamine, cytokines or TNF- ⁇ , it must meet one of the following characteristics:
  • + for histamine receptor antagonists an inhibition of the contraction of smooth muscles induced by the administration of histamine
  • cytokine receptor antagonists inhibition of macrophage adhesion induced by cytokines on endothelial cells or inhibition of release of superoxide anions induced by cytokines on neutrophils;
  • TNF- ⁇ receptor antagonists inhibition of macrophage adhesion induced by TNF- ⁇ on endothelial cells or inhibition of TNF- ⁇ -induced release of superoxide anions on neutrophils or inhibition of mitogenic activity TNF- ⁇ on fibroblasts of the dermis.
  • the histamine H1 receptor antagonists which can be used in the invention are those conventionally used in the treatment of allergic and anaphylactic conditions as well as those for combating motion sickness. These compounds can be, for example, derivatives of diethylene diamine such as Cinnarizine, eyelizine; aminopropane derivatives such as dexchloro-pheniramine, triprolidine; phenothiazine derivatives such as promethazine, alimemazine; as well as the compounds cited on pages 116 to 118 of the book Joseph R. Prous, The Year's Drug News, Therapeutic Targets, 1994 edition, Prous Science Publishers such as cetirizine HCI, ebastine, loratadine, setastine HCI.
  • Histamine release inhibitors include compounds oxygenated or sulfur heterocyclic compounds such as furan derivatives, benzofuran derivatives, thiophene derivatives and benzothiophene derivatives, optionally comprising nitrogen substituents, such as those described in documents US-A-4931459, US-A-4910317 and EP-A-299457, and more especially the alkoxy- and / or aryloxy-tetrazol-yl-benzofuran-carboxamides or the alkoxy- and / or aryloxy-tetrazol-yl-benzothiophene-carboxamides.
  • an interleukin-1 release antagonist which can be used in the invention which may be auranofine or SKF-105809 or else an interleukin-1 antagonist which may be lactoferrin, or even peptides or peptide derivatives, natural or synthetic, such as for example melanotropin type ⁇ or these derivatives such as for example the tripeptide Lys-Pro-Val.
  • TNF- ⁇ receptor antagonists and the TNF- ⁇ release and / or synthesis inhibitors which can be used in the invention are in particular lisophyline, I ⁇ 802715, sulfasalazine.
  • Histamine, cytokine and TNF-a antagonists can be synthesized or extracted from natural products (plants or animals).
  • histamine, cytokine and TNF- ⁇ antagonists can be used, separately or in combination, alone or in the form of a mixture.
  • the compounds reducing the synthesis, the release and / or the activity of at least one inflammation mediator can be used, separately or in combination, alone or in the form of a mixture.
  • the amount of compound decreasing the synthesis, the release and / or the activity of at least one mediator of the inflammation contained in the composition of the invention is of course a function of the desired effect and can therefore vary to a large extent.
  • the composition of the invention may contain a compound which decreases the synthesis, the release and / or the activity of at least one inflammation mediator in an amount representing from 0.001% to 5% of the total weight of the composition and preferably in an amount representing from 0.01% to 2% of the total weight of the composition.
  • the amount of inhibitor of a sodium channel or of a calcium channel contained in the composition is of course a function of the desired effect and can therefore vary to a large extent.
  • the inhibitor of a sodium channel or of a calcium channel is in an amount representing from 0.0001% to 10% of the total weight of the composition and preferably in an amount representing from 0.001% to 5% of the total weight of the composition.
  • compositions according to the invention can be presented in all the galenical forms normally used, particularly for topical application.
  • composition according to the invention can be applied to the skin (on any cutaneous zone of the body), the scalp, the nails or the mucous membranes (buccal, jugale, gingival, genital, conjunctiva). Depending on the mode of administration, the composition according to the invention can be in all the dosage forms normally used.
  • the composition may take the form in particular of an aqueous or oily solution or of a dispersion of the lotion or serum type, of emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersion of a phase fatty in an aqueous phase (O / W) or vice versa (W / O), or of suspensions or emulsions of soft consistency of the aqueous or anhydrous cream or gel type, or of microcapsules or microparticles, or of vesicular dispersions of the ionic type and /or not ionic.
  • These compositions are prepared according to the usual methods.
  • They can also be used for the scalp in the form of aqueous, alcoholic or hydroalcoholic solutions, or in the form of creams, gels, emulsions, foams or also in the form of aerosol compositions also comprising a propellant under pressure.
  • compositions according to the invention are those conventionally used in the fields considered.
  • compositions constitute in particular cleansing, protective, treatment or care creams for the face, for the hands, for the feet, for large anatomical folds or for the body (for example day creams, night creams, make-up remover creams, foundation creams, sunscreen creams), fluid foundations, make-up removal milks, body protection or care milks, anti-sun milks, lotions, gels or foams for care of the skin, such as cleansing lotions, sunscreen lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, aftershave gels or lotions, depilatory creams, compositions against insect bites, pain relieving compositions, compositions for treating certain skin diseases such as eczema, rosacea, psoriasis, lichens, severe pruritus.
  • compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars.
  • compositions can also be packaged in the form of an aerosol composition also comprising a propellant under pressure.
  • the composition according to the invention can also be a composition for hair care, and in particular a shampoo, a styling lotion, a treating lotion, a styling cream or gel, a composition of dyes (in particular oxidation dyes) in the form of coloring shampoos, restructuring hair lotions, a perm composition (in particular a composition for the first time of a perm), a fall prevention lotion or gel, an antiparasitic shampoo, etc.
  • the composition can also be for oral use, for example a toothpaste.
  • the composition may contain adjuvants and additives customary for compositions for oral use and in particular surfactants, thickening agents, humectants, polishing agents such as silica, various active ingredients such as fluorides, in particular particularly sodium fluoride, and optionally sweetening agents such as sodium saccharinate.
  • the proportion of the fatty phase can range from 5% to 80% by weight, and preferably from 5% to 50% by weight relative to the total weight of the composition.
  • the oils, waxes, emulsifiers and coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the cosmetic field.
  • the emulsifier and the coemulsifier are present in the composition in a proportion ranging from 0.3% to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.
  • the emulsion may, in addition, contain lipid vesicles.
  • the fatty phase can represent more than 90% of the total weight of the composition.
  • the cosmetic composition may also contain adjuvants customary in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters, odor absorbers and coloring matters.
  • adjuvants customary in the cosmetic field such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters, odor absorbers and coloring matters.
  • the amounts of these various adjuvants are those conventionally used in the cosmetic field, and for example from 0.01% to 10% of the total weight of the composition.
  • These adjuvants depending on their nature, can be introduced into the fatty phase, into the aqueous phase and / or into the lipid spherules.
  • emulsifiers which can be used in the invention, mention may, for example, be made of glycerol stearate, polysorbate 60 and the mixture of PEG-6 / PEG-32 / Glycol Stearate sold under the name Tefose® 63 by the company Gattefosse.
  • solvents which can be used in the invention mention may be made of lower alcohols, in particular ethanol and isopropanol, propylene glycol.
  • hydrophilic gelling agents which can be used in the invention, mention may be made of carboxyvinyl polymers (carbomers), acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, ethylcellulose, polyethylene.
  • carboxyvinyl polymers carboxyvinyl polymers
  • acrylic copolymers such as acrylate / alkyl acrylate copolymers
  • polyacrylamides polysaccharides
  • polysaccharides such as hydroxypropylcellulose
  • natural gums and clays and, as lipophilic gelling agents
  • modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica
  • composition may contain other hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids.
  • hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids.
  • retinol and its derivatives
  • tocopherol vitamin E
  • essential fatty acids ceramides
  • essential oils ceramides
  • the composition may combine at least one inhibitor of a sodium channel or of a calcium channel with other active agents intended in particular for the prevention and / or treatment of skin conditions.
  • active agents there may be mentioned by way of example:
  • agents modulating differentiation and / or proliferation and / or skin pigmentation such as retinoic acid and its isomers, retinol and its esters, vitamin D and its derivatives, estrogens such as estradiol, kojic acid or hydroquinone; - antibacterials such as clindamycin phosphate, erythromycin or antibiotics of the tetracycline class;
  • - antiparasitics in particular metronidazole, crotamiton or pyrethroids
  • - antifungals in particular compounds belonging to the class of imidazoles such as econazole, ketoconazoie or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allylamine family, such as terbinafine, or octopirox;
  • - antiviral agents such as acyclovir
  • - steroidal anti-inflammatory agents such as hydrocortisone, betamethasone valerate or clobetasol propionate, or non-steroidal anti-inflammatory agents such as ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid , acetaminophen or glycyrrhetinic acid
  • non-steroidal anti-inflammatory agents such as ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid , acetaminophen or glycyrrhetinic acid
  • - anesthetic agents such as lidocaine hydrochloride and its derivatives
  • - antipruritic agents such as thenaldine, trimeprazine or cyproheptadine;
  • - keratolytic agents such as alpha- and beta-hydroxycarboxylic or beta-ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, salicylic acid, citric acid and generally fruit acids, and n-octanoyl-5-salicylic acid;
  • - anti-free radical agents such as alpha-tocopherol or its esters, superoxide dismutases, certain metal chelators or ascorbic acid and its esters;
  • anti-dandruff agents such as octopirox or zinc pyrithione
  • - anti-acne drugs such as retinoic acid or benzoyl peroxide.
  • the invention relates to a composition containing at least one inhibitor of a sodium channel or of a calcium channel and at least one agent chosen from antibacterial, antiparasitic, antifungal, antiviral, anti-inflammatory agents, antipruritic, anesthetics, keratolytics, anti-free radicals, anti-seborrheic, anti-dandruff, anti-acne and / or agents modulating differentiation and / or proliferation and / or skin pigmentation.
  • the inhibitor of a sodium channel or of a calcium channel can be used in the preparation of cosmetic and / or pharmaceutical compositions, particularly dermatological.
  • a subject of the invention is also a method of cosmetic treatment of the skin, comprising the topical application to the skin of a topical cosmetic composition in accordance with the invention, to increase the tolerance threshold of the skin or to prevent, treat , or even remove, tingling, tingling, itching or pruritus, burning, feelings of heating, discomfort, tightness and / or redness and / or erythema.
  • the process of the invention applies particularly well to sensitive skin or to intolerant skin.
  • the cosmetic treatment methods of the invention can be implemented in particular by applying the hygienic or cosmetic compositions as defined above, according to the usual technique for using these compositions. For example: application of creams, gels, serums, lotions, cleansing milks or anti-sun compositions on the skin or on dry hair, application of a hair lotion on wet hair, shampoos, or further application of toothpaste on the gums.
  • compositions illustrate the invention without limiting it in any way.
  • proportions indicated unless otherwise indicated are percentages by weight
  • An in vivo functional test is carried out to measure the effectiveness of an agent inhibiting cationic ionic conductance on an inflammation of neurogenic origin induced by electrical stimulation which causes a phenomenon comparable to cellular hyperexcitability.
  • the in vivo experiments are carried out according to the method described by Xu XJ and collaborators (Neurosciences, 1991, 42, 731-737).
  • the test consists of causing neurogenic inflammation by antidromic stimulation of the saphenous nerve in the anesthetized animal. This nerve innervates the skin areas of the hind legs.
  • Neurogenic inflammation is quantified by measuring tissue permeability with Evans blue, a marker for tissue extravasation of plasma albumin that occurs during inflammation.
  • a calcium channel blocker verapamil
  • Spantide II (0.03 ⁇ moles), is used in the test as a positive reference
  • Control sterile water p: significance test according to the Newman Keuls method.
  • Verapamil causes a statistically significant decrease of 66% in neurogenic inflammation.
  • Example 2 Examples of compositions according to the invention. These compositions are obtained by the usual techniques commonly used in cosmetics or in pharmacy.
  • Composition 1 Body care cream
  • Polysorbate 60 (Tween 60 sold by the company HERE) 1.00
  • Composition 2 Face care cream (oil in water emulsion)
  • Polysorbate 60 (Tween 60 sold by the company HERE) 1.00
  • Composition 3 Face care cream (oil in water emulsion)
  • Polysorbate 60 (Tween 60 sold by the company HERE) 1.00
  • Composition 4 Facial care cream for sensitive skin (oil in water emulsion) Amiloride 0.30
  • Polysorbate 60 (Tween 60 sold by the company HERE) 1.00 U
  • Composition 5 Face care cream for sensitive skin (oil in water emulsion)
  • Polysorbate 60 (Tween 60 sold by the company ICI) 1.00 Stearic acid 1.40

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP99937868A 1998-03-06 1999-02-25 Verwendung von calcium- oder natrium-kanal-blockern enthaltende zusammensetzung zur topische anwendung Withdrawn EP1059912A2 (de)

Applications Claiming Priority (3)

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FR9802783A FR2775594B1 (fr) 1998-03-06 1998-03-06 Utilisation d'un compose inhibant l'activite d'un canal sodium ou d'un canal calcium dans une composition a usage topique
FR9802783 1998-03-06
PCT/FR1999/000430 WO1999044579A2 (fr) 1998-03-06 1999-02-25 Utilisation d'un compose inhibant l'activite d'un canal sodium ou d'un canal calcium dans une composition a usage topique

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US6610683B2 (en) * 1996-09-12 2003-08-26 Idun Pharmaceuticals, Inc. Treatment of infectious disease using interleukin-1β-converting enzyme (ICE)/CED-3 family inhibitors
RU2161480C1 (ru) * 1999-11-04 2001-01-10 Щеткина Наталья Иосифовна Способ приготовления состава для талассотерапии
FR2815539B1 (fr) * 2000-10-23 2003-02-14 Silab Sa Principe actif riche en isoflavones, son procede d'extraction et ses applications cosmetiques
FR2823669B1 (fr) 2001-04-23 2004-03-26 Oreal Procede pour augmenter le seuil de tolerance d'une peau sensible ou intolerante
EP1749528A1 (de) * 2005-08-05 2007-02-07 Pharma C S.A. Pharmazeutische Kombinationen, welche mu-opioid Agonisten und Inhibitoren der Stickstoffmonoxidherstellung enthalten
GB0619176D0 (en) * 2006-09-29 2006-11-08 Lectus Therapeutics Ltd Ion channel modulators & uses thereof
WO2010110428A1 (ja) * 2009-03-27 2010-09-30 協和発酵キリン株式会社 掻痒の予防及び／または治療剤
KR101099550B1 (ko) * 2009-04-02 2011-12-28 대한민국 봉독을 유효성분으로 하는 상처 또는 화상 치료용 조성물
JP5562716B2 (ja) 2010-05-12 2014-07-30 花王株式会社 電位依存性カチオンチャネル抑制剤
EP2638908A1 (de) * 2012-03-16 2013-09-18 Phytotox SpA Paralytische Schalentiervergiftung
CN105233286B (zh) * 2015-09-10 2018-10-30 上海交通大学医学院 含酸敏感离子通道调控剂的制剂及其在治疗瘙痒中的用途

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JP2529571B2 (ja) * 1987-05-12 1996-08-28 株式会社ヤクルト本社 皮膚刺激感抑制剤及びこれを配合してなる化粧料
JPH01238509A (ja) * 1988-03-16 1989-09-22 Shiseido Co Ltd 皮膚外用剤
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JP2002505268A (ja) 2002-02-19
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