USRE46228E1 - Pigmentation-regulating compounds - Google Patents

Pigmentation-regulating compounds Download PDF

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USRE46228E1
USRE46228E1 US14/175,312 US200814175312A USRE46228E US RE46228 E1 USRE46228 E1 US RE46228E1 US 200814175312 A US200814175312 A US 200814175312A US RE46228 E USRE46228 E US RE46228E
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agent
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Juan Cebrián Puche
Ángel Messeguer Peypoch
Antonio Vicente Ferrer Montiel
Nuria Almiñana Doménech
Cristina Carreño Serraïma
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Lipotec SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
    • C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • 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
    • A61Q19/04—Preparations for care of the skin for chemically tanning the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q3/00—Manicure or pedicure preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • 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
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists

Definitions

  • the present invention relates to 6-substituted 7-methoxy-2,2-dimethylchromanes and to cosmetic or pharmaceutical compositions containing these compounds for treating, caring for and/or cleaning skin, hair and/or nails, preferably for attenuating the degree of pigmentation of the skin and the hair or for treating spots on nails or for photoprotection of the skin, hair and nails.
  • the modification of the natural pigmentation of the skin is a desirable fact for several reasons for many people in America, Asia or Europe. Some of the reasons for modifying the natural color of the skin include the search for lighter skin as a model of beauty, and the elimination or attenuation of spots on the skin such as freckles or lentigines.
  • Dysfunctions in the melanin production mechanism due to external aggressions, exposure to UV radiation, inflammations, hormonal disturbances, pregnancy (melasma), photoageing or ageing induce hyperpigmentation and the occurrence of brown spots, particularly in the form of freckles or solar or senile lentigines.
  • melanocytes are cells of neuroectodermal origin that are bound by dendrites to the cells of the basal layer of the epidermis at a proportion of approximately one melanocyte for every ten basal cells, regardless of race.
  • the main function of the melanocyte is to synthesize the melanin through cellular and hormonal interaction.
  • Melanin is a dark pigment found in the skin, hair, eyes and certain nerve cells and protects the body from the harmful effects of ultraviolet radiation.
  • melanin pigments There are two types of melanin pigments, eumelanin and pheomelanin.
  • Eumelanin is black, while pheomelanin has a lighter color, between reddish and yellow.
  • Skin and hair tone is determined by the proportion of one or another type of pigment. These pigments accumulate in melanosomes in the melanocyte cytoplasm and are carried by the melanosomes to dendrites where they are injected in the basal cell cytoplasm. A homogenous melanin distribution in the basal layer of the epidermis thus occurs, giving uniform pigmentation of the skin [Hearing V. J.
  • hair color depends on the amount and the quality of the melanin located in the cortex of the hair stalk. Said melanin is produced by the melanocytes located at the base of the root and depends on hereditary, hormonal, nutritional factors, etc. Over the years, the amount of melanin of the hair decreases due to the reduction of melanocyte activity, justifying the whitening of hair (gray hair).
  • Melanosomes are formed by, among others, melanin and melanoprotein, which is a product of the interaction with the enzyme tyrosinase.
  • Tyrosinase is a glycoprotein located in the membrane of melanosomes and catalyzes to first steps in formation of pigment, i.e. the ortho-hydroxylation of the amino acid tyrosine which produces L-dopa and the oxidation of the latter to give dopaquinone [Hearing V. G. and Tsukamoto K. (1991) “Enzymatic control of pigmentation in mammals” FASEB J. 5:2902-2909].
  • dopaquinone reacts in a eumelanogenesis or pheomelanogenesis process. If cysteine levels are low, dopaquinone is converted into eumelanin by autoxidation processes. If cysteine levels are high, dopaquinone combines with cysteine to form cysteinyldopa, which is subsequently modified to generate pheomelanin.
  • Melanin pigmentation of the skin can be divided into several causal components: 1) cutaneous melanin generated according to genetic programs in the absence of exposure to ultraviolet rays (constitutive skin color) and 2) immediate and delayed tanning reactions induced by direct exposure of the skin to UV radiation (facultative skin color).
  • the changes in facultative color are a result of the interaction between sunlight, hormones and the tanning capacity, the latter being dependent on the genetic constitution of each individual.
  • hyperpigmentation areas Some of the causes of hyperpigmentation include hormonal alterations, melasma, lentigo, piebaldism, Addison's disease, hypersensitivity to ultraviolet radiation due to agents favoring the action of radiation (phototoxins), or hyperpigmentation resulting from an inflammatory lesion. Spots associated to acne, eczemas, scars or depilation belong to this latter type of hyperpigmentation and these spots can last even several years.
  • Irregularities in pigmentation of the skin can also be caused by exposure to environmental factors. Exposure of the skin, especially Caucasian skin, to ultraviolet radiation, particularly UVB, promotes the synthesis of endogenous tyrosinase, resulting in an increase of melanogenesis and therefore in skin tanning. However, persistent exposure to UVB radiation can result in the formation of cancerous hyperpigmented lesions or melanomas [Dooley T. P. (1994) “Recent advances in cutaneous melanoma oncogenesis research” Onco. Res. 6:1-9] as well as in non-malignant hyperpigmented spots due to photoageing.
  • melanin distribution in the epidermal cell layers it is even possible to inhibit melanin distribution in the epidermal cell layers or to cause melanin degradation by means of melanogenesis inhibitors which interact with enzyme tyrosinase or with any other enzyme involved in melanogenesis.
  • depigmenting agents which allow restoring spots or freckles to a normal skin color and therefore allow reducing the signs of ageing and of photoageing.
  • skin depigmentation or lightening was done using very strong products such as hydroquinones or derivatives thereof, particularly their ethers such as monomethyl ether and monoethyl ether. Though these compounds show certain efficacy, they have adverse effects due to their toxicity, even making them hazardous.
  • hydroquinone for example, is irritating and cytotoxic for melanocytes, causes irreversible hypopigmentation, subsequently increasing photosensitization in areas of the skin exposed to UV radiation and has shown indications of mutagenicity [Glatt H., Padykula R., Berchtold G. A., Ludewig G., Platt K. L., Klein J. and Oesch F. (1989) “Multiple activation pathways of benzene leading to products with varying genotoxic characteristics” Environ Health Perspect 82:81-89; Glatt H. R. (1990) “Endogenous mutagens derived from amino acids.” Mutat. Res.
  • Topical retinoids and corticosteroids have also been proposed as whitening agents, although they have failed to provide a favorable response.
  • Arbutin and its derivatives are also used, though they are only marginal tyrosinase inhibitors and have little bioavailability.
  • Other widely used depigmenting agents are vitamin C and its derivatives, such as ascorbyl-2-phosphate magnesium salt (MAP) or ascorbyl-2-phosphate sodium salt (NAP) for example, although they basically have the same instability drawbacks in formulations as those described for kojic acid.
  • MAP ascorbyl-2-phosphate magnesium salt
  • NAP ascorbyl-2-phosphate sodium salt
  • compositions use natural product extracts, some of which have been used as whitening agents for centuries in Asia or in Europe, such as lemon, orange, ginkgo, cucumber, geranium, bearberry, carob bean, cinnamon, marjoram, rosemary, clove, blackberry or licorice extracts.
  • natural product extracts some of which have been used as whitening agents for centuries in Asia or in Europe, such as lemon, orange, ginkgo, cucumber, geranium, bearberry, carob bean, cinnamon, marjoram, rosemary, clove, blackberry or licorice extracts.
  • the variety of active ingredients in the extracts of these natural products and the possible allergic reactions of natural products occasionally limit the use of these natural agents.
  • Solar filters protect the skin from UVB radiation, which can cause bums, and from UVA radiation, which causes long-term damage to the skin causing accelerated ageing or photoageing.
  • Solar filters are classified into 1) chemical filters containing chemical compounds absorbing UV radiation and emitting it in the form of low-energy radiation that is not harmful for the skin, 2) physical filters containing opaque materials reflecting UV radiation or 3) biological filters preventing the formation of free radicals and enhance the cutaneous immunological system.
  • 6-substituted 7-methoxy-2,2-dimethylchromanes are capable of reducing the amount of melanin produced by the melanocytes by means of the inhibition of the enzyme tyrosinase and, in turn, to protect against damage caused by UV radiation.
  • Patent document JP 2001-002558 describes cosmetic compositions of 6,7-disubstituted 2,2-dialkylchromanes or 6,7-disubstituted 2,2-dialkylchromenes with hydroxy, methoxy or 2-trifluoroethoxy groups having a whitening effect and an effect of increasing the permeability of the epidermal barrier due to the fact that these compounds inhibit melanogenesis and sebaceous secretion in the skin.
  • Patent documents EP 1430879 A2, EP 1430933 A2 and EP 1336403 A1 describe the use of 6,7-disubstituted 2,2-dialkylchromanes or 6,7-disubstituted 2,2-dialkylchromenes with hydroxy, methoxy or 2-trifluoroethoxy groups in cosmetic deodorant or antiperspirant compositions, in compositions for treating hair loss and in compositions with anti-inflammatory activity, respectively.
  • Patent applications EP 1002533 A1 and EP 1430882 A2 describe cosmetic or dermatological compositions of 6,7-disubstituted 2,2-dimethylchromanes with hydroxy, methoxy or 2-trifluoroethoxy groups, alone or combined with other antioxidants, respectively.
  • Patent documents EP 1634576 A1 and EP 1343465 A2 describe, among others, cosmetic compositions, 6-hydroxy-7-methoxy-2,2-dimethylchromane compositions (Lipochroman-6 marketed by Lipotec S.A.) or 6-hydroxy-7-methoxy-2,2-dimethylchromene combined with DNA-repair enzymes.
  • Lipochroman-6 as an antioxidant agent inhibitor of lipid peroxidation in cosmetic or dermatological compositions is also known [Puig A. (2002) “Synthetic actives for cosmetic applications” Specialty Chemicals Magazine 2002, 22(10):16-17].
  • Lipochroman-6 also acts as an oxygen-reactive radical species scavenger [Sanvicens N., Gomez-Vicente V., Masip I., Messeguer A. and Cotter T. G. (2004) “Oxidative stress-induced apoptosis in retinal photoreceptor cells is mediated by calpains and caspases and blocked by the oxygen radical scavenger CR-6” J. Biol. Chem.
  • patent document EP 1267813 A2 describes Lipochroman-6 cosmetic compositions as an MMP-1 matrix metalloprotease inhibitor.
  • Patent documents WO 01/82888 A1, WO 02/05778 A1 and WO 02/47655 A1 describe Lipochroman-6 compositions alone or combined with other compounds, wherein Lipochroman-6 is an NO-synthase inhibitor.
  • Particularly patent document WO 01/82888 also describes the use of its compositions to inhibit melanogenesis induced by ultraviolet radiation and/or the treatment of hypermelanosis-type disorders.
  • 6-heptyloxy-7-methoxy-2,2-dimethylchromene and 6-lauroyl-7-methoxy-2,2-dimethylchromene compounds obtained from 6-hydroxy-7-methoxy-2,2-dimethylchromene are known in the state of the art.
  • the 6-heptyloxy-7-methoxy-2,2-dimethylchromane or 6-lauroyl-7-methoxy-2,2-dimethylchromane analogues are not known.
  • the present invention provides a novel solution to the existing needs and comprises the discovery of 6-substituted 7-methoxy-2,2-dimethylchromanes with an ester or thioester group with 3 to 24 carbon atoms (C 3 -C 24 ) capable of treating those conditions, disorders and/or pathologies of the skin, hair and/or nails which require regulating the degree of pigmentation in a safer and more effective manner than the whitening compounds already known in the state of the art.
  • the present invention provides a simple, effective and risk-free solution for treating, caring for and/or cleaning skin, hair and/or nails, comprising applying on the skin, hair and/or nails of a mammal a 6-substituted 7-methoxy-2,2-dimethylchromane.
  • the object of the present invention is also a cosmetic or pharmaceutical composition containing at least one 6-substituted 7-methoxy-2,2-dimethylchromane of formula (I) and a cosmetically or pharmaceutically acceptable medium.
  • a first aspect of the invention relates to a 6-substituted 7-methoxy-2,2-dimethylchromane compound according to general formula (I):
  • Preferred structures of the compounds depicted in general formula (I) are those in which R is a linear, saturated or unsaturated aliphatic group with from 2 to 23 carbon atoms (C 2 to C 23 ) or R is an alicyclic cyclic group, an aromatic cyclic group or a heterocyclic cyclic group.
  • Preferred structures of the compounds depicted in general formula (I) are those in which X is O.
  • tert-butanoyl is an aliphatic group selected from the group consisting of tert-butanoyl, 2-methylhexanoyl, hexanoyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl or linoleoyl.
  • —CO—(CH 2 ) 0-6- phenyl is an alicyclic, aromatic or heterocyclic cyclic group selected from the group consisting of —CO—(CH 2 ) 0-6- phenyl, —CO—(CH 2 ) 0-6- (1-naphthyl), —CO—(CH 2 ) 0-6- (2-naphthyl), —CO—(CH 2 ) 0-6- CH(phenyl) 2 , —CO-(2-fluorophenyl), —CO-cyclohexyl, ⁇ -lipoyl, L-prolyl, D-prolyl, biotinyl —CO-(4-imidazolyl), —CO-(2-pyridyl), —CO-(2-thienyl), —CO-(2-furyl) or —CO-(3-furyl).
  • aliphatic group relates to a linear or branched, saturated or unsaturated hydrocarbon group.
  • hydrocarbon group is used in the present invention to comprise, for example and in a non-limiting sense, alkyl, alkenyl and alkynyl groups.
  • alkyl group relates to a saturated, linear or branched hydrocarbon group, including, for example and in a non-limiting sense, methyl, ethyl, isopropyl, isobutyl, tertbutyl, heptyl, dodecyl, hexadecyl, octadecyl, amyl, 2-ethylhexyl, 2-methylhexyl, 2-methylbutyl, 5-methylhexyl and the like.
  • alkenyl group relates to an unsaturated, linear or branched hydrocarbon group with one or more carbon-carbon double bonds such as, for example and in a non-limiting sense, the vinyl, oleyl, linoleyl group and the like.
  • alkynyl group relates to an unsaturated, linear or branched hydrocarbon group with one or more carbon-carbon triple bonds.
  • cyclic group relates to a closed hydrocarbon ring which can be classified as an alicyclic, aromatic or heterocyclic group.
  • alicyclic group relates to a cyclic hydrocarbon group with properties similar to aliphatic groups, including, for example and in a non-limiting sense, cyclopropyl, cyclopentyl, cyclohexyl and the like.
  • aromatic group or the term “aryl group” relate to a mono- or polycyclic aromatic hydrocarbon group or to an aralkyl group.
  • aralkyl group relates to an alkyl group substituted with one or more aromatic groups, including, for example and in a non-limiting sense, —(CH 2 ) 1-6- phenyl, —(CH 2 ) 1-6- (1-naphthyl), —(CH 2 ) 1-6- (2-naphthyl), —(CH 2 ) 1-6- CH(phenyl) 2 and the like.
  • heterocyclic group relates to a closed hydrocarbon ring in which one or more than one of the atoms of the ring is an element other than carbon, such as nitrogen, oxygen or sulfur for example, or an heteroalkyl group.
  • heteroalkyl group relates to an alkyl group substituted with a heterocyclic group, including, for example and in a non-limiting sense, —(CH 2 ) 1-6- imidazolyl, —(CH 2 ) 1-6- thienyl, —(CH 2 ) 1-6 -furyl, —(CH 2 ) 1-6- pyrrolidinyl and the like.
  • substitution can therefore exist in the compounds of the present invention.
  • group and block will be used to differentiate between chemical species which allow substitution or which can be substituted (“group”), and those which do not allow substitution or which cannot be substituted (“block”).
  • aliphatic group will include not only aliphatic substituents, but also aliphatic substituents containing other substituents known in the state of the art, such as hydroxy, alkoxy, amino, carboxyl, halogen atoms, cyano, nitro, alkylsulfonyl, and others.
  • aliphatic group includes ether, haloalkyl, alcohol, thiol, carboxyl, amine, hydroxyalkyl, sulfoalkyl and guanidine groups and others.
  • aliphatic block is limited only to the inclusion of aliphatic substituents, such as propyl, isobutyl, octyl, decyl, lauryl, myristyl, palmityl, stearyl, oleyl, linoleyl and the like.
  • cosmetically or pharmaceutically acceptable salts of the compounds provided by this invention are within the scope of the present invention.
  • the term “cosmetically or pharmaceutically acceptable salts” include the salts normally used to form base addition salts, whether they are metallic, such as and in a non-limiting sense lithium, sodium, potassium, calcium, magnesium or aluminum among others for example, or organic, such as and in a non-limiting sense ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine or piperazine among others for example, or acid addition salts, whether they are organic, such as and in a non-limiting sense acetate, citrate, oleate, trifluoroacetate, oxalate or gluconate among others for example, or inorganic, such as and in a non-limiting sense chloride, sulfate, borate or carbonate among others for example.
  • the nature of the salt is not critical provided that it is cosmetically or pharmaceutically acceptable.
  • the cosmetically or pharmaceutically acceptable salts of the compounds of the invention can be obtained by conventional methods well-known in the state of the art [Berge S. M., Bighley L. D. and Monkhouse D. C. (1977) “Pharmaceutical Salts” J. Pharm. Sci. 66:1-19].
  • the compounds object of the present invention can be synthesized according to conventional methods known in the state of the art, such as for example by esterification or thioesterification reactions starting from 6-hydroxy-7-methoxy-2,2-dimethylchromane and the compound of general formula (II), which is the acid or thioacid of the corresponding aliphatic or cyclic group or a reactive derivative thereof.
  • a fragment of the compound of general formula (I) having a free hydroxyl group or a reactive derivative thereof is reacted with a complementary fragment of general formula (II) having a carboxyl or thiocarboxyl group or a reactive derivative thereof, with the subsequent formation of an ester or thioester bond, and in which said fragments have the functional groups that do not participate in the formation of the ester or thioester bond, if any, duly protected with temporary or permanent protecting groups.
  • protecting groups, their insertion and their elimination are described in the literature [Greene T. W. and Wuts P. G. M.
  • protecting groups also includes polymeric supports used in solid phase synthesis.
  • the compounds of the invention or their cosmetically or pharmaceutically acceptable salts can be administered for treating, caring for and/or cleaning skin, hair and/or nails by any means producing contact of the compounds with the action site thereof in the body of a mammal, preferably in a human being, in the form of a composition that contains them.
  • the invention provides cosmetic or pharmaceutical compositions comprising at least one compound of general formula (I) or its cosmetically or pharmaceutically acceptable salts together with at least one cosmetically or pharmaceutically acceptable adjuvant.
  • Said compositions can be prepared by means of conventional methods known by persons skilled in the art [Wilkinson J. B. and Moore R. J.
  • the compounds of the present invention can also be adsorbed on solid organic polymers or solid mineral supports such as, for example and in a non-limiting sense talc, bentonite, silica, starch and/or maltodextrin among others.
  • solid organic polymers or solid mineral supports such as, for example and in a non-limiting sense talc, bentonite, silica, starch and/or maltodextrin among others.
  • compositions containing the compounds of the present invention or their cosmetically or pharmaceutically acceptable salts can be used in different types of formulations for topical or transdermal application such as, for example and in a non-limiting sense, creams, oil and/or silicone in water emulsions, water in oil and/or silicone emulsions, water/oil or silicone/water type emulsions, oil or silicone/water/oil or silicone type emulsions, oils, milks, balsams, foams, lotions, hydroalcoholic solutions, gels, liniments, serums, soaps, ointments, mousses, salves, powders, bars, pencils or sprays or aerosols, including leave on and rinse-off formulations, and they can also be incorporated by means of techniques known by persons skilled in the art in different types of solid accessories such as, for example and in a non-limiting sense towelettes, hydrogels, adhesive (or non-adhesive) patches or face masks, or they can be incorporated
  • compositions containing the compounds of the present invention or their cosmetically or pharmaceutically acceptable salts can also be incorporated in products for treating, caring for and/or cleaning nails such as, for example and in a non-limiting sense polishes, nail polish removal lotions or cuticle removal lotions.
  • compositions containing the compounds of the invention or their cosmetically or pharmaceutically acceptable salts can be administered in addition to topically or transdermally, by any other type of suitable administration method, for example by oral, nasal, parenteral or rectal administration, to which end they will include the cosmetically or pharmaceutically acceptable excipients necessary for the formulation of the desired dosage form.
  • parenteral includes subcutaneous, intradermal, intravascular injections such as, for example and in a non-limiting sense intravenous, intramuscular, spinal, intracranial, intraarticular, intratecal and intraperitoneal, as well as any other similar injection or infusion technique.
  • the cosmetic compositions containing the compounds of the present invention or their cosmetically or pharmaceutically acceptable salts can be used in different types of formulations for their oral administration, particularly in the form of oral cosmetics such as, for example and in a non-limiting sense, in capsules, including gelatin capsules, tablets, including sugar-coated tablets, powders, granulated forms, chewing gums, solutions, suspensions, emulsions, syrups, jellies or gelatins, as well as in any other presentation known by a person skilled in the art.
  • the compounds of the invention can be incorporated in any form of functional food or enriched food such as, for example and in a non-limiting sense, in dietary bars or in compact or non-compact powders.
  • Said powders can be solubilized in water, soda, dairy products, soy derivatives or they can be incorporated in dietary bars.
  • the compounds of the present invention or their cosmetically or pharmaceutically acceptable salts can be formulated with the usual excipients and adjuvants for oral compositions or food supplements such as, for example and in a non-limiting sense, fatty components, aqueous components, wetting agents, preservatives, texturizing agents, flavors, aromas, antioxidants and/or colorants common in the food sector.
  • the compounds of the invention or their cosmetically or pharmaceutically acceptable salts can also previously be incorporated in cosmetic or pharmaceutical sustained release systems and/or carriers such as liposomes, milliparticles, microparticles and nanoparticles, as well as in sponges, vesicles, micelles, millispheres, microspheres and nanospheres, lipospheres, millicapsules, microcapsules and nanocapsules, as well as in microemulsions and nanoemulsions, for the purpose of obtaining greater penetration of the active ingredient and/or improving the pharmacokinetic and pharmacodynamic properties thereof.
  • cosmetic or pharmaceutical sustained release systems and/or carriers such as liposomes, milliparticles, microparticles and nanoparticles, as well as in sponges, vesicles, micelles, millispheres, microspheres and nanospheres, lipospheres, millicapsules, microcapsules and nanocapsules, as well as in microemulsions and nanoemulsions, for the purpose
  • the controlled release formulations can be prepared by means of methods known in the state of the art and can be administered, for example, by topical administration, including adhesive patches, or by oral, parenteral, rectal administration or subcutaneous implantation or by direct implantation in a specific part of the body, and they must preferably release a relatively constant amount of the compounds of the invention.
  • the amount of compound contained in the controlled release formulation will depend on, for example, the administration site, the kinetics and the duration of the release of the compound of the invention.
  • the compounds of general formula (I) or their cosmetically or pharmaceutically acceptable salts are used in the cosmetic or pharmaceutical compositions of the present invention at cosmetically or pharmaceutically effective concentrations to obtain the desired effect; preferably between 0.00000001% (by weight) and 20% (by weight); preferably between 0.00001% (by weight) and 10% (by weight) and more preferably between 0.0001% (by weight) and 5% (by weight).
  • the cosmetically or pharmaceutically effective amount of the compounds according to the invention or of their cosmetically or pharmaceutically acceptable salts which must be administered to regulate the amount of melanin, as well as their dosage, will depend on a number of factors, including age, degree of pigmentation, administration method and frequency and particularly on the nature of the compounds that are used.
  • the cosmetically or pharmaceutically acceptable adjuvants contained in the cosmetic or pharmaceutical compositions described in the present invention include the additional ingredients commonly used in compositions for treating, caring for and/or cleaning skin, hair and/or nails such as, for example and in a non-limiting sense, other agents inhibiting melanin synthesis, other whitening or depigmenting agents, anti-ageing agents, agents inhibiting NO-synthase, antioxidants, anti-atmospheric pollution and/or free radical trapping agents, anti-glycation agents, emulsifying agents, emollients, organic solvents, liquid propellants, skin conditioners such as for example wetting agents, moisture retaining substances, alpha hydroxy acids, moisturizers, vitamins, pigments or colorants, dyes, gelling polymers, thickeners, surfactants, softeners, anti-wrinkle agents, agents capable of reducing or eliminating bags under the eyes, exfoliating agents, antimicrobial agents, antifungal agents, bactericides, agents stimulating dermal or epidermal
  • additional ingredients must not unacceptably alter the benefits of the compounds of the present invention.
  • Said additional ingredients may be of a synthetic or natural origin, such as for example plant extracts, or they can be derived from a biofermentation process. Additional examples are described in CTFA Cosmetic Ingredient Handbook, Eleventh Edition (2006).
  • the compounds of the present invention can be used in combination with solar filters (UVA or UVB radiation blockers) to prevent repigmentation, to protect the skin from exposure to the sun or from tanning induced by exposure to the sun, or to increase their capacity to reduce the amount of melanin in the skin and its depigmenting action.
  • solar filters UVA or UVB radiation blockers
  • solar filters include, for example and in a non-limiting sense, p-aminobenzoic acid derivatives, benzylidene camphor derivatives, cinnamic acid derivatives, benzothiazole derivatives, benzimidazole derivatives, benzophenone derivatives, triazine derivatives, salicylic acid derivatives, dibenzoylmethane derivatives, ⁇ , ⁇ -diphenylacrylate derivatives, as well as nanopigments such as, for example and in a non-limiting sense, titanium oxide nanopigments, iron oxide nanopigments, zinc oxide nanopigments, zirconium oxide nanopigments or cerium oxide nanopigments, among others.
  • the compounds of the present invention can also be used in combination with desquamating agents capable of promoting exfoliation of the skin for the purpose of obtaining greater efficacy in the depigmenting treatment.
  • desquamating agents include the use of alpha hydroxy acids such as, for example and in a non-limiting sense, glycolic acid, lactic acid, citric acid, tartaric acid, malic acid and/or mandelic acid among others, beta hydroxy acids such as, for example and in a non-limiting sense salicylic acid and derivatives thereof; as well as the use of urea and derivatives thereof, resveratrol, N-acetylglucosamine, jasmonic acid and derivatives thereof, cinnamic acid, gentisic acid, oligofucoses, Saphora japonica extract, detergents and/or enzymes such as, for example and in a non-limiting sense, sutilains, papaya extract, bromelain, pineapple extract, pumpkin extract and/or sweet potato extract, among
  • the compounds object of the present invention have variable solubility in water, depending on the nature of the R and X groups in general formula (I). Those compounds that are not soluble in water can be solubilized in cosmetically or pharmaceutically acceptable conventional solvents such as, for example and in a non-limiting sense, ethanol, propanol or isopropanol, propyleneglycol, glycerin, butylene glycol or polyethylene glycol, or in any combination thereof or combination thereof with water.
  • cosmetically or pharmaceutically acceptable conventional solvents such as, for example and in a non-limiting sense, ethanol, propanol or isopropanol, propyleneglycol, glycerin, butylene glycol or polyethylene glycol, or in any combination thereof or combination thereof with water.
  • compositions containing the compounds of the invention or their cosmetically or pharmaceutically acceptable salts can be administered orally or topically or transdermally and they can be presented in any dosage form, for example, solid, liquid or semisolid, to which end they will include the pharmaceutically acceptable excipients necessary for the formulation of the desired dosage form [Faul ⁇ i Trill° C. (1993) in “Tratado de Farmacia Galénica”, Luzán 5, S.A. Ediations, Madrid].
  • the cosmetic or pharmaceutical compositions of the invention can include agents which increase percutaneous absorption of the compounds of the present invention such as, for example and in a non-limiting sense, dimethylsulfoxide, dimethylacetamide, dimethylformamide, surfactants, azone, alcohol, acetone, propyleneglycol or polyethylene glycol, among others.
  • the cosmetic or pharmaceutical compositions object of the present invention can be applied in the local areas to be treated by means of iontophoresis, sonophoresis, electroporation, steam wrap, microinjections or needleless injections by means of pressure such as, for example and in a non-limiting sense, oxygen pressure injections, for the purpose of obtaining greater penetration of the active ingredient.
  • the compounds of the invention or their cosmetically or pharmaceutically acceptable salts can also be incorporated into fabrics for making garments that are in direct contact with the skin of the body, such that they release the compounds of the invention either by biodegradation of the system for anchoring them to the fabric or by the friction of the garments against the body, due to body moisture, the pH of the skin or the body temperature.
  • fabrics and means for immobilizing the compounds in the fabrics, including microencapsulation are described in the literature and are known in the state of the art [Schaab C. K. (1986) “Impregnating Fabrics With Microcapsules” HAPPI May 1986; Nelson G. (2002) “Application of microencapsulation in textiles” Int. J. Pharm. 242:55-62].
  • the preferred garments of the present invention are bandages, gauzes, pantyhose, socks, gloves or sleeves for the arms and forearms.
  • An additional aspect of the present invention relates to a cosmetic or pharmaceutical composition containing a cosmetically or pharmaceutically effective amount of at least one compound of the invention or its cosmetically or pharmaceutically acceptable salts, and furthermore a cosmetically or pharmaceutically effective amount of at least one extract with depigmenting activity such as, for example and in a non-limiting sense, Achillea millefolium, Aloe vera, Azadirachta indica, Osmunda japonica, Artocarpus incisus, Bidens pilosa, Broussonetia papyrifera, Chlorella vulgaris, Cimicifuga racemosa, Emblica officinalis, Glycyrrhiza glabra, Glycyrrhiza uralensis, Ilex purpurea, Ligusticum lucidum, Ligusticum wallichii, Mitracarpus scaber, Morinda citrifolia, Morus alba, Morus bombycis, Naringi crenul
  • Another aspect of the present invention relates to a cosuretic or pharmaceutical method to treat those conditions of mammals, preferably humans, requiring pigmentation regulation, comprising the administration of an effective amount of at least one compound of general formula (I) or its cosmetically or pharmaceutically acceptable salts, preferably in the form of a cosmetic or pharmaceutical composition which contains them.
  • the present invention further provides a cosmetic or pharmaceutical method to whiten or lighten the skin, preferably the skin of the face and/or the hands.
  • the present invention provides a cosmetic or pharmaceutical method to treat those conditions, disorders and/or pathologies of the skin relating to regulation of pigmentation, preferably freckles, lentigo, melasma, piebaldism, Addison's disease, vitiligo, spots due to exposure to UV radiation, spots due to ageing or to photoageing, spots of an inflammatory origin and especially post-laser treatment or post-aesthetic surgery inflammations, spots due to acne, to eczemas, to ochronosis, to scars and/or to hormonal disorders such as chloasmas for example, which comprises applying on the skin a cosmetic or pharmaceutical composition containing at least one compound of the invention or its cosmetically or pharmaceutically acceptable salts.
  • the present invention further provides a cosmetic or pharmaceutical method to depigment facial and/or body hair as well as to lighten the color of the hair which comprises applying on the scalp or on those areas of the human body with hair, a cosmetic or pharmaceutical composition containing at least one compound of the invention or its cosmetically or pharmaceutically acceptable salts.
  • a cosmetic or pharmaceutical method to qualify skin pigmentation irregularities preferably the areas of the skin adjacent to the areas affected by vitiligo, reducing the contrast between both areas, which comprises applying on the skin a cosmetic or pharmaceutical composition containing at least one compound of the invention or its cosmetically or pharmaceutically acceptable salts.
  • the present invention further provides a cosmetic or pharmaceutical method to photoprotect skin, hair and nails which comprises applying on the skin, hair and/or nails a cosmetic or pharmaceutical composition containing at least one compound of the invention or its cosmetically or pharmaceutically acceptable salts.
  • the present invention further provides a cosmetic or pharmaceutical method to treat spots on nails which comprises applying on the nails a cosmetic or pharmaceutical composition containing at least one compound of the invention or its cosmetically or pharmaceutically acceptable salts.
  • the application frequency of the cosmetic or pharmaceutical composition comprising at least one compound of the invention or its cosmetically or pharmaceutically acceptable salts may significantly vary, depending on the needs of each subject, an application range from once a month up to 10 times a day being suggested, preferably from once a week up to 4 times a day, more preferably from three times a week up to three times a day, even more preferably one or two times a day.
  • An additional aspect of the present invention relates to the use of at least one of the compounds of general formula (I) or its cosmetically or pharmaceutically acceptable salts in preparing a cosmetic or pharmaceutical composition for treating, caring for and/or cleaning skin, hair and/or nails preferably the skin of the face, neck, neck-line, hands, axillae, groin, elbows and/or knees and more preferably local areas of the face, neck and/or hands.
  • the present invention relates to the use of at least one of the compounds of general formula (I) or its cosmetically or pharmaceutically acceptable salts in preparing a cosmetic or pharmaceutical composition for lightening or evening out pigmentation of the skin.
  • the present invention relates to the use of at least one of the compounds of general formula (I) or its cosmetically or pharmaceutically acceptable salts in preparing a cosmetic or pharmaceutical composition for treating spots on the skin.
  • the present invention relates to the use of at least one of the compounds of general formula (I) or its cosmetically or pharmaceutically acceptable salts in preparing a cosmetic or pharmaceutical composition for treating or preventing ageing or photoageing of the skin.
  • Another additional aspect of the present invention relates to the use of at least one of the compounds of general formula (I) or its cosmetically or pharmaceutically acceptable salts in preparing a cosmetic or pharmaceutical composition for photoprotecting the skin, hair and/or nails.
  • Another additional aspect of the present invention relates to the use of at least one of the compounds of general formula (I) or its cosmetically or pharmaceutically acceptable salts in preparing a cosmetic or pharmaceutical composition for lightening or depigmenting facial and/or body hair.
  • Another additional aspect of the present invention relates to the use of at least one of the compounds of general formula (I) or its cosmetically or pharmaceutically acceptable salts in preparing a cosmetic or pharmaceutical composition for treating spots on nails.
  • the present invention provides a cosmetic or pharmaceutical depigmenting or whitening method, comprising the administration of an effective amount of at least one of the compounds of general formula (I) or its cosmetically or pharmaceutically acceptable salts, and preferably in the form of a cosmetic or pharmaceutical composition which contains it.
  • DNA deoxyribonucleic acid
  • QSF quantity sufficient for; DCC, N,N-dicyclohexylcarbodiimide; DMAP, dimethylaminopyridine; DMSO, dimethylsulfoxide; DMEM, Dulbecco's modified Eagle's medium; DPPC, dipalmitoylphosphatidylcholine; equiv., equivalents; ESI-MS, electrospray ionization mass spectrometry; FBS, fetal bovine serum; HEPES, N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid; HPLC, high performance liquid chromatography; MAP, ascorbyl-2-phosphate magnesium salt; MLU, multilaminar vesicles; MW, molecular weight; PMA, 1-methoxy-2-propyl acetate; ULV, unilaminar vesicles; UV ultraviolet; UVA, ultraviolet radiation type A; UVB, ultraviolet radiation type
  • 6-hydroxy-7-methoxy-2,2-dimethylchromane (5.0 g; 24.0 mmol, 1 equiv.) was reacted with 1 equiv. of the corresponding carboxylic or thiocarboxylic acid in the presence of DMAP (2.0 mmol, 0.083 equiv.) and DCC (24.0 mmol, 1 equiv.) in dichloromethane at room temperature, performing controls by thin layer chromatography. When it was observed that the reaction stopped progressing the formed dicyclohexylurea was filtered and evaporated to dryness.
  • Phase A The components of Phase A were are weighed in a large enough reactor and the mixture is heated to 70° C. to melt the waxes.
  • the components of Phase B are weighed in a suitable container for the entire content.
  • the components of Phase C are added to Phase B and heated to 70° C. under intense stirring.
  • Phase A is slowly added to the preceding mixture under stirring and the mixture is maintained under stirring for 30 minutes at 70° C. It is left to cool under gentle stirring and when the mixture is at room temperature, xanthan gum and fragrance are added, the mixture is homogenized and the pH is corrected with triethanolamine if needed.
  • the cream that is obtained has a pH between 5.5 and 6.
  • Dipalmitoylphosphatidylcholine (DPPC), cholesterol and 7-methoxy-6-palmitoyl-2,2-dimethylchromane are weighed and dissolved in chloroform.
  • the solvent is evaporated under vacuum until obtaining a thin phospholipid layer, and this is hydrated by treating at 55° C. with an aqueous solution containing Phenonip®, obtaining the MLV liposomes.
  • the ULV liposomes are obtained by submerging the MLV liposomes in an ultrasound bath at 55° C. for 8 2-minute cycles at 5 minute intervals. To reduce the size even more, it can be passed through an extrusion system under high pressure.
  • INGREDIENT (INCI Nomenclature) % BY WEIGHT DIPALMITOYLPHOSPHATIDYLCHOLINE 8.0 7-methoxy-6-palmitoyl-2,2-dimethylchromane 1.0 CHOLESTEROL 3.0 PHENOXYETHANOL, METHYLPARABEN, 0.5 ETHYLPARABEN, BUTYLPARABEN, PROPYLPARABEN, ISOBUTYLPARABEN AQUA (WATER) 87.5
  • the liposomes of example 3 are dispersed in water with preservatives (EDTA, imidazolidinyl urea and Phenonip®) under gentle stirring. Hispagel® 200 [INCI Aqua, Glycerin and Glyceryl polyacrylate] is added and it is gently stirred until a homogenous mixture is obtained.
  • preservatives EDTA, imidazolidinyl urea and Phenonip®
  • INGREDIENT (INCI Nomenclature) % BY WEIGHT LIPOSOMES CONTAINING 10.00 7-methoxy-6-palmitoyl-2,2-dimethylchromane (1%) DISODIUM EDTA 0.15 IMIDAZOLIDINYL UREA 0.10 AQUA (WATER), GLYCERIN, 60.00 GLYCERYL POLYACRYLATE AQUA (WATER) 29.25 PHENOXYETHANOL, METHYLPARABEN, 0.50 ETHYLPARABEN, BUTYLPARABEN, PROPYLPARABEN, ISOBUTYLPARABEN
  • INGREDIENT (INCI Nomenclature) % BY WEIGHT PHASE A MINERAL OIL 10.00 PETROLATUM 1.00 BEESWAX (CERA ALBA) 2.00 7-methoxy-6-palmitoyl-2,2-dimethylchromane 0.50 CETEARETH-25 2.00 DIMETHICONE 0.20 C24-28 ALKYL METHICONE 0.10 CETEARYL ALCOHOL 2.00 PHASE B DISODIUM EDTA 0.15 AQUA (WATER) QSF 100 PHENOXYETHANOL, METHYLPARABEN, 0.50 ETHYLPARABEN, BUTYLPARABEN, PROPYLPARABEN, ISOBUTYLPARABEN IMDDAZOLEDINYL UREA 0.10 CARBOMER 0.35 GLYCERINE 3.00 PHASE C PARFUME (FRAGRANCE) 0.10 PHASE F TRIETHANOLAMINE QSF
  • the assay is performed in 96 well plates and the samples are performed in triplicate.
  • the control sample contains 80 ⁇ L of buffer (150 mM HEPES), 10 ⁇ L of mushroom tyrosinase of 10 ⁇ g/ ⁇ L and 10 ⁇ L of 10 mM L-Dopa substrate.
  • the positive control further contains kojic acid at a concentration of 0.1 mM.
  • the samples of 7-methoxy-6-palmitoyl-2,2-dimethylchromane and 6-hydroxy-7-methoxy-2,2-dimethylchromane (Lipochroman-6) contain instead of kojic acid, the compounds at a concentration of 1 mM.
  • the samples thus prepared are incubated at 37° C. for 10 minutes. Then the plate containing the samples is cooled for 5 minutes on ice to stop the enzymatic reaction. To quantify the melanin produced it is measured in the plate reader at a length of 492 nm.
  • Table 1 measures the percentage of melanin formed normalized in relation to the control sample for the comparative sample with kojic acid and for the sample with 7-methoxy-6-palmitoyl-2,2-dimethylchromane and for the Lipochroman-6 sample.
  • the human melanocytes are cultured in DMEM medium supplemented with 10% FBS, 1% penicillin/streptomycin and 100 nM PMA.
  • the compound 7-methoxy-6-palmitoyl-2,2-dimethylchromane is dissolved in 1:1 DMSO:sterile water at a final concentration of 10 mM.
  • the endogenous tyrosine of the human melanocytes seeded at a confluence of 95% is extracted.
  • the assay is performed after extracting and quantifying the enzymatic content.
  • Such assay consists of incubating the tyrosinase enzyme for 30 minutes with Lipochroman-6 (1 mM), 7-methoxy-6-palmitoyl-2,2-dimethylchromane (1 mM) or with kojic acid (0.1 mM) as a comparative agent.
  • the synthetic L-Dopa (10 mM) substrate is added, measuring absorbance at a wavelength of 475 nm one hour after having added L-Dopa. This measurement allows evaluating the melanin content produced.
  • Table 2 measures the percentage of melanogenesis in relation to a control sample, one hour after having added L-Dopa, for the comparative sample with kojic acid and for the samples with 7-methoxy-6-palmitoyl-2,2-dimethylchromane and with Lipochroman-6.
  • the human melanocytes seeded in confluence are cultured for 5 days adding fresh medium daily containing 0.1 mM of kojic acid or of 7-methoxy-6-palmitoyl-2,2-dimethylchromane.
  • the melanin content was is seen directly by means of microscopy using a 40 magnification lens.
  • the depigmenting efficacy was is determined by counting the number of cells containing melanin and the total number of cells, and the obtained results were are normalized in relation to the whitening efficacy of a control sample.
  • the human keratinocytes were maintained in culture for 24 hours in 96 well plates to form monolayers and the cells were pre-incubated in the dark with 150 ⁇ g/mL of 7-methoxy-6-palmitoyl-2,2-dimethylchromane or saline phosphate buffer (control) for one hour at 37° C. and humidified air with 5% CO 2 .
  • the cells were then irradiated with a solar simulation lamp with an energy of 37 J/cm 2 at room temperature for 150 minutes.
  • a control plate was maintained in the dark for the same time at room temperature.
  • the medium of the cells was replaced after the irradiation period with fresh medium and the cells were incubated for 24 additional hours.
  • the cell viability was determined by means of the Neutral Red dye, measuring the optical density at 540 nm in a spectrophotometer.
  • the photoprotecting efficacy was determined by comparing the viability obtained in the cells treated with 7-methoxy-6-palmitoyl-2,2-dimethylchromane in relation to the response of the irradiated and non-irradiated control cells.

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Families Citing this family (24)

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EP2316416B1 (de) 2009-10-28 2015-12-23 PM-International AG Hautaufhellende kosmetische Zusammensetzung
KR101688815B1 (ko) * 2010-08-13 2016-12-23 (주)아모레퍼시픽 프로판노이드 유도체를 함유하는 백모 방지용 및 백반증 치료용 조성물
JP6005397B2 (ja) * 2012-05-18 2016-10-12 株式会社コーセー 皮膚外用剤
CN102670480B (zh) * 2012-06-08 2013-05-22 钟春燕 一种控油保湿修复体膜及制备方法
CN102697702B (zh) * 2012-06-08 2013-04-17 钟春燕 一种美白保湿修复体膜及制备方法
DE102012222970A1 (de) * 2012-12-12 2014-06-12 Henkel Ag & Co. Kgaa Wirkstoffkombination zur Hautaufhellung I
EP2789369B1 (en) * 2013-04-14 2018-06-06 Symrise AG A composition for lightening skin and hair
US9226890B1 (en) 2013-12-10 2016-01-05 Englewood Lab, Llc Polysilicone base for scar treatment
DE102014211185A1 (de) * 2014-06-11 2015-12-17 Henkel Ag & Co. Kgaa Kosmetische Zusammensetzungen zur Hautaufhellung
WO2016014529A1 (en) * 2014-07-21 2016-01-28 Wisys Technology Foundation, Inc. Skin lightening compounds
CN106999372A (zh) * 2014-09-29 2017-08-01 Elc 管理有限责任公司 用于刺激角质形成细胞的分化以美白色素沉着过度的皮肤的活性物
EP3212688B1 (en) * 2014-10-31 2022-04-13 Lubrizol Advanced Materials, Inc. Thermoplastic polyurethane film for delivery of active agents to skin surfaces
JP6594661B2 (ja) * 2015-05-25 2019-10-23 月桂冠株式会社 新規染色剤原料の製造方法
FR3036617B1 (fr) * 2015-05-27 2018-08-31 L'oreal Derives (1-phenyl-2-phenyl) ethylene polyhydroxyles a titre d'agent anti-age et photoprotecteur
US20180311358A1 (en) 2015-11-05 2018-11-01 Lubrizol Advanced Materials, Inc. Thermoformable dual network hydrogel compositions
US10493020B2 (en) 2016-04-14 2019-12-03 The Procter & Gamble Company Method of improving the appearance of periorbital dyschromia
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Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS52147433A (en) * 1976-06-02 1977-12-07 Fuji Photo Film Co Ltd Color photographic light sensitive material
EP0655239A1 (en) 1993-11-25 1995-05-31 Lipotec, S.A. Liposomes encapsulating doxorubicine
EP1002533A1 (en) 1998-09-16 2000-05-24 Lipotec, S.A. Use of chromanes and/or chromenes derivatives to prevent oxidative reactions induced by free radicals
JP2001002558A (ja) 1999-04-19 2001-01-09 Kanebo Ltd 美白化粧料
WO2001074320A2 (de) 2000-03-31 2001-10-11 Henkel Kommanditgesellschaft Auf Aktien Verwendung von protease-inhibitoren in der kosmetik und pharmazie
WO2001082888A1 (fr) 2000-04-28 2001-11-08 L'oreal Lipochroman-6 comme inhibiteur de no-synthase et utilisations
WO2002005778A1 (fr) 2000-07-13 2002-01-24 L'oreal Composition, notamment cosmetique, comprenant la dhea et/ou un precurseur ou derive de celle-ci, en association avec au moins un inhibiteur de no-synthase
WO2002047655A1 (fr) 2000-12-15 2002-06-20 L'oreal Composition, notamment cosmetique, comprenant la 7-hydroxy dhea et/ou la 7-ceto dhea et au moins un inhibiteur de no-synthase
WO2002049593A2 (de) 2000-12-20 2002-06-27 Henkel Kommanditgesellschaft Auf Aktien Verwendung von dna-reparatur-enzymen als mmp-1-inhibitoren
EP1260509A1 (fr) * 2001-05-25 2002-11-27 Derma Developpement S.A.R.L. Utilisations d'esters de tocophérol
US6569906B1 (en) * 1998-03-10 2003-05-27 Pierre Fabre Dermo-Cosmetique Composition containing a precursor capable of being hydrolysed by glucocerebrosidase
EP1336403A1 (de) 2002-02-15 2003-08-20 Henkel Kommanditgesellschaft auf Aktien 6,7-disubstituierte 2,2-Dialkylchromane oder -chromene als Entzündungshemmer
EP1430933A2 (de) 2002-12-20 2004-06-23 Henkel Kommanditgesellschaft auf Aktien Kosmetische und pharmazeutische Zusammensetzungen enthaltend Steroidsulfatase-Inhibitoren und deren Verwendung zur Verminderung von Haarausfall
EP1430882A2 (de) 2002-12-16 2004-06-23 Henkel Kommanditgesellschaft auf Aktien Antioxidans-Kombinationen mit 6,7-disubstituierten 2,2-Dialkylchromanen oder -chromenen
EP1430879A2 (de) 2002-12-20 2004-06-23 Henkel Kommanditgesellschaft auf Aktien Arylsulfatase-Inhibitoren in Deodorantien und Antitranspiratien
EP1634576A1 (de) 2004-08-13 2006-03-15 Henkel Kommanditgesellschaft auf Aktien Kosmetische und dermatologische Zusammensetzungen mit DNA-Reparaturenzymen und Oligopeptiden

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4162326A (en) * 1978-09-27 1979-07-24 Stauffer Chemical Company Insect control agents

Patent Citations (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS52147433A (en) * 1976-06-02 1977-12-07 Fuji Photo Film Co Ltd Color photographic light sensitive material
EP0655239A1 (en) 1993-11-25 1995-05-31 Lipotec, S.A. Liposomes encapsulating doxorubicine
US5605703A (en) * 1993-11-25 1997-02-25 Lipotec, S.A. Liposomes encapsulating doxorubicin
US6569906B1 (en) * 1998-03-10 2003-05-27 Pierre Fabre Dermo-Cosmetique Composition containing a precursor capable of being hydrolysed by glucocerebrosidase
EP1002533A1 (en) 1998-09-16 2000-05-24 Lipotec, S.A. Use of chromanes and/or chromenes derivatives to prevent oxidative reactions induced by free radicals
JP2001002558A (ja) 1999-04-19 2001-01-09 Kanebo Ltd 美白化粧料
EP1267813A2 (de) 2000-03-31 2003-01-02 Henkel Kommanditgesellschaft auf Aktien Verwendung von protease-inhibitoren in der kosmetik und pharmazie
WO2001074320A2 (de) 2000-03-31 2001-10-11 Henkel Kommanditgesellschaft Auf Aktien Verwendung von protease-inhibitoren in der kosmetik und pharmazie
WO2001082888A1 (fr) 2000-04-28 2001-11-08 L'oreal Lipochroman-6 comme inhibiteur de no-synthase et utilisations
US7008630B2 (en) * 2000-04-28 2006-03-07 L' Oreal Lipochroman-6 as NO-synthase inhibitor and uses
US20050238613A1 (en) 2000-07-13 2005-10-27 L'oreal Composition, in particular cosmetic, comprising DHEA and/or a precursor or derivative thereof, combined with at least a no-synthase inhibitor
WO2002005778A1 (fr) 2000-07-13 2002-01-24 L'oreal Composition, notamment cosmetique, comprenant la dhea et/ou un precurseur ou derive de celle-ci, en association avec au moins un inhibiteur de no-synthase
WO2002047655A1 (fr) 2000-12-15 2002-06-20 L'oreal Composition, notamment cosmetique, comprenant la 7-hydroxy dhea et/ou la 7-ceto dhea et au moins un inhibiteur de no-synthase
US20030223982A1 (en) 2000-12-20 2003-12-04 Kordula Schlotmann Use of DNA repair enzymes as MMP 1 inhibitors
EP1343465A2 (de) 2000-12-20 2003-09-17 Henkel Kommanditgesellschaft auf Aktien Verwendung von dna-reparatur-enzymen als mmp-1-inhibitoren
WO2002049593A2 (de) 2000-12-20 2002-06-27 Henkel Kommanditgesellschaft Auf Aktien Verwendung von dna-reparatur-enzymen als mmp-1-inhibitoren
EP1260509A1 (fr) * 2001-05-25 2002-11-27 Derma Developpement S.A.R.L. Utilisations d'esters de tocophérol
EP1336403A1 (de) 2002-02-15 2003-08-20 Henkel Kommanditgesellschaft auf Aktien 6,7-disubstituierte 2,2-Dialkylchromane oder -chromene als Entzündungshemmer
EP1430882A2 (de) 2002-12-16 2004-06-23 Henkel Kommanditgesellschaft auf Aktien Antioxidans-Kombinationen mit 6,7-disubstituierten 2,2-Dialkylchromanen oder -chromenen
EP1430933A2 (de) 2002-12-20 2004-06-23 Henkel Kommanditgesellschaft auf Aktien Kosmetische und pharmazeutische Zusammensetzungen enthaltend Steroidsulfatase-Inhibitoren und deren Verwendung zur Verminderung von Haarausfall
EP1430879A2 (de) 2002-12-20 2004-06-23 Henkel Kommanditgesellschaft auf Aktien Arylsulfatase-Inhibitoren in Deodorantien und Antitranspiratien
EP1634576A1 (de) 2004-08-13 2006-03-15 Henkel Kommanditgesellschaft auf Aktien Kosmetische und dermatologische Zusammensetzungen mit DNA-Reparaturenzymen und Oligopeptiden

Non-Patent Citations (31)

* Cited by examiner, † Cited by third party
Title
Atherton, E., et al., "Solid Phase Peptide Synthesis: A practical approach," IRL Press Oxford University, UK, pp. 1-61 (1984).
Benmaman, O., et al., "Treatment and camouflaging of pigmentary disorders," Clin. Dermatol, pp. 50-61 (1988).
Berge, S. M., et al., "Pharmaceutical Salts," J. Pharm. Sci. 66, pp. 1-19 (1977).
Boehnlein et al. Characterization of esterase and alcohol dehydrogenase activity in skin. Metabolism of retinyl palmitate to rentinol (vitamin A) during percutaneous absorption. Pharmaceutical Research, 1994, 11(8):1155-1159. *
Cebrián, J., et al., "New anti-RNS and -RCS products for cosmetic treatment," Int. J. Cosm. Science 27(5), pp. 271-278 (2005).
Dooley, T. P., "Is there room for a moderate level of regularity oversight?" in "Drug Discovery Approaches for Developing Cosmeceuticals: Advanced Skin Care and Cosmetic Products," Ed. Hori W, Chapter 1.4, International Business Communications, pp. 1.4.1-1.4.16(1997).
Dooley, T. P., "Recent advances in cutaneous melanoma oncogenesis research," Onco. Res. 6: pp. 1-9 (1994).
Dooley, T. P., "Topical skin depigmentation agents: Current products and discovery of novel inhibitors of melanogenesis," J. Dermatol. Treat. 8, pp. 275-279 (1997).
Fleisher, et al., "Improved oral drug delivery: solubility limitations overcome by the use of prodrugs," Advanced Drug Delivery Reviews, vol. 19, pp. 115-130 (1996).
Glatt, H. R., "Endogenous mutagens derived from amino acids," Mutat. Res. 238, pp. 235-243 (1990).
Glatt, H., et al., "Multiple activation pathways of benzene leading to products with varying genotoxic characteristics," Environ. Health Perspect. 82, pp. 81-89 (1989).
Greene, T. W., et al., in "Protective groups in organic synthesis", John Wiley & Sons, pp. 308-405 (1981).
Hearing, V.J., "Biochemical control of melanogenesis and melanosomal organization," J. Invest. Dermatol. Symp. Proc. 4, pp. 24-28 (1999).
Hearing, V.J., et al., "Enzymatic control of pigmentation in mammals," FASEB J. 5, pp. 2902-2909 (1991).
International Search Report for PCT/ES2008/000230, dated Dec. 2, 2008.
Kuwabara, Y., et al., "Topical Application of gamma-Tocopherol Derivative Prevents UV-Induced Skin Pigmentation," Biol. Pharm. Bull, vol. 29(6), pp. 1175-1179 (2006).
Kuwabara, Y., et al., "Topical Application of γ-Tocopherol Derivative Prevents UV-Induced Skin Pigmentation," Biol. Pharm. Bull, vol. 29(6), pp. 1175-1179 (2006).
Lipochroman-6. CODE:ES290. Skin cell damage prevention by RNS scavenging. Lipotec S.A. Feb. 2005. *
Meredith, P., et al., "Radiative Relaxation Quantum Yields for Synthetic Eumelanin," Photochem. Photobiol. 79, pp. 211-216 (2004).
Nakagawa, M., et al., "Contact allergy to kojic acid in skin care products," Contact Dermatitis 42, pp. 9-13 (1995).
Nelson, G., "Application of microencapsulation in textiles," Int. J. Pharm. 242, pp. 55-62 (2002).
Piérard, G. E., et al., "Pigmentary changes in skin senescence," J. Appl. Cosmetol. 9, pp. 57-63 (1991).
Puig A. Synthetic actives for cosmetic applications. Specialty Chemicals Magazine, 2002, 22(107):16-17. *
Puig, A. "Synthetic actives for cosmetic applications," Specialty Chemicals Magazine 2002, 22(10), pp. 16-17 (2002).
Sanvicens, N., et al., "Oxidative stress-induced apoptosis in retinal photoreceptor cells is mediated by calpains and caspases and blocked by the oxygen radical scavenger CR-6," J. Biol. Chem. 279(38), pp. 39268-39278 (2004).
Schaab, C.K., "Impregnating Fabrics With Microcapsules" HAPPI, pp. 84-86 (May 1986.
Schallreuter, K. U., "Epidermal adrenergic signal transduction as part of the neuronal network in the human epidermis," J. Invest. Dermatol. 2, pp. 37-40 (1997).
Silverman RB. The Organic Chemistry of Drug Design and Drug Action. Academic Press, Inc. 1992, pp. 352-356. *
Stefanaki, C., et al., "Topical retinoids in the treatment of photoaging," J. Cosmet. Dermatol. 4, pp. 130-134 (2005).
Wilkinson, J.B., et al., "Harry's Cosmetology," Longman Scientific & Technical, London, UK pp. 50-73, and 757-799 (1982).
Yenes, S., et al. "A Study of the Reaction of Difference Phenol Substrates with Nitric Oxide and Peroxynitrite," Tetrahedon, vol. 55, pp. 14111-14122 (1999).

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11779532B2 (en) 2020-06-12 2023-10-10 Mary Kay Inc. Topical compositions and methods

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