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WO2015011311A1 - Combinaison pour réduire l'hyperpigmentation de la peau - Google Patents

Combinaison pour réduire l'hyperpigmentation de la peau Download PDF

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Publication number
WO2015011311A1
WO2015011311A1 PCT/ES2014/070362 ES2014070362W WO2015011311A1 WO 2015011311 A1 WO2015011311 A1 WO 2015011311A1 ES 2014070362 W ES2014070362 W ES 2014070362W WO 2015011311 A1 WO2015011311 A1 WO 2015011311A1
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WO
WIPO (PCT)
Prior art keywords
composition
topical
oral
skin
combination
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Ceased
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PCT/ES2014/070362
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English (en)
Spanish (es)
Inventor
Carles Trullàs Cabanas
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Isdin SA
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Isdin SA
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Classifications

    • 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
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/13—Coniferophyta (gymnosperms)
    • A61K36/15—Pinaceae (Pine family), e.g. pine or cedar
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
    • 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
    • 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
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9755—Gymnosperms [Coniferophyta]
    • A61K8/9767—Pinaceae [Pine family], e.g. pine or cedar
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • 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
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/88—Two- or multipart kits
    • A61K2800/884—Sequential application
    • 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
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/92—Oral administration

Definitions

  • This invention relates to the field of skin care compositions. More specifically, it refers to a method to reduce skin hyperpigmentation.
  • the invention relates to the combined use of an oral composition and a topical composition for said use.
  • Melanin in humans is primarily responsible for skin color.
  • Melanin is produced by the melanocytes of the epidermis in response to environmental factors, such as sun exposure. Different environmental or physiological causes can cause disorders in the production of melanin.
  • Non-homogeneous pigmentation of the skin is a cause of concern for its unwanted aesthetic effects, which causes cosmetics to be sought in order to mitigate these effects.
  • UV radiation is the main cause of pigment spots due to the sun.
  • hyperpigmentation of the skin such as melasma
  • Melasma has a strong impact on the quality of life of affected individuals since injuries occur mainly on the face. These spots are easier to appear in certain situations, such as skins that have already had pigmentary disorders, pregnant women, people who are under the use of photosensitizing medications such as some contraceptives and compromised skin after a dermatological procedure.
  • the main actions in melasma therapy are to provide protection against ultraviolet light, retard the proliferation of melanocytes, inhibit the formation of melanin and melanosomes and promote the degradation of melanin in melanosomes.
  • topical formulations with color is an important part of the Treatment in subjects with hyperpigmentation of the skin.
  • antioxidants play an important role in the treatment of hyperpigmentation as well as in the protection of the skin from the sun.
  • Proanthocyanidins, and in particular Pycnogenol® often give topical formulations a difficult color to mask, whose application on the skin is an additional aesthetic problem for the population suffering from skin hyperpigmentation.
  • a topical formulation that included all the active ingredients of interest, including proanthocyanidins would not allow the color of the formulation to be customized according to the needs of each skin phototype and, therefore, would not cover this aspect of the treatment of the subjects.
  • the present invention provides a combination of compositions and an application method to decrease skin hyperpigmentation that provides a much greater effect than currently known formulations.
  • the inventors have surprisingly found that a hyperpigmentation decrease effect, such as in melasma, can be achieved by combining oral administration of a composition comprising pine bark extract and grape seed extract with administration topically of a composition comprising phenylethylresorcinol, niacinamide and tetrapeptide-30.
  • Said combination allows to increase the selectivity of action without producing a depigmenting effect in non-lesional or perilesional areas, so that a homogeneous effect of skin tone modulation occurs.
  • one aspect of the present invention relates to the use of a combination comprising pine bark extract and grape seed extract for the preparation of an oral composition A to decrease the hyperpigmentation of the skin in a human, where said composition is administered sequentially or separately in combination with a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30 together with one or more pharmaceutically acceptable excipients and / or carriers for topical use.
  • a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30 together with one or more pharmaceutically acceptable excipients and / or carriers for topical use.
  • This aspect can be formulated as an oral composition A that comprises pine bark extract and grape seed extract together with one or more components acceptable for oral use to decrease hyperpigmentation of the skin in a human, where said composition is administered sequentially or separately in combination with a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30.
  • a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30.
  • This aspect can also be formulated as a method to decrease the hyperpigmentation of the skin in a subject, where the method comprises a) the administration to said subject of a safe and effective amount of an oral composition A comprising pine bark extract and extract of grape seed together with one or more components acceptable for oral use, in combination with b) administration in the hyperpigmented skin area of a safe and effective amount of a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30 together with one or more acceptable components for topical use.
  • an oral composition A comprising pine bark extract and extract of grape seed together with one or more components acceptable for oral use
  • a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30 together with one or more acceptable components for topical use.
  • compositions of the invention are intended for use in reducing hyperpigmentation of certain areas of the skin, especially the skin of the face, in order to obtain a homogeneous hue of the skin and in accordance with the coloring of the areas of the skin that has not undergone hyperpigmentation and thus improve the appearance of the skin.
  • the combination of the active ingredients of the pine bark extract and the grape seed extract included in the oral administration composition allows a wider range of proanthocyanidins to be applied, which provides greater antioxidant protection.
  • the concomitant use of the aforementioned oral administration composition and the topical administration composition allows treating hyperpigmentation subjects with a combination of active ingredients that act directly on the skin spots, while protecting the skin from direct effects of sun exposure that worsen or cause skin hyperpigmentation.
  • Oral intake of antioxidants allows improve the level of antioxidant activity of the cells, making them less susceptible to the action of the sun's rays.
  • said specific combination of active ingredients produces an unexpected effect in the hyperpigmented areas of the skin due to the synergistic effect produced by the joint action through two different routes of administration.
  • the combined use of the two products allows a more constant treatment and a more uniform effect than in their separate application not combined. In this way the final action of the joint treatment is more effective than the non-combined application of the oral and topical products separately.
  • the components of the combination of the invention must be in a safe and effective amount to produce the effect of diminishing the hyperpigmentation of the skin and homogenize its hue.
  • compositions can be prescribed to be used in conjunction with the other composition to decrease skin hyperpigmentation.
  • one aspect of the invention provides the use of a combination comprising pine bark extract and grape seed extract for the preparation of an oral composition A to decrease the hyperpigmentation of the skin in a human, where said composition is to be administered in combination with a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30 together with one or more components acceptable for topical use.
  • a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30 together with one or more components acceptable for topical use.
  • composition A which comprises a safe and effective amount of pine bark extract and grape seed extract together with one or more components acceptable for oral use to decrease skin hyperpigmentation in a human, where said composition is for be administered in combination with a composition B comprising a safe and effective amount of phenylethylresorcinol, niacinamide and tetrapeptide-30 together with one or more components acceptable for topical use.
  • the invention provides the use of a combination comprising phenylethylresorcinol, niacinamide and tetrapeptide-30 for the preparation of a topical composition B to decrease hyperpigmentation of the skin in a human, wherein said composition is to be administered in combination with an oral composition A comprising pine bark extract and grape seed extract together with one or more components acceptable for oral use.
  • composition B comprising a safe and effective amount of phenylethylresorcinol, niacinamide and tetrapeptide-30 together with one or more acceptable components for topical use to decrease skin hyperpigmentation in a human, where said composition is for be administered in combination with a composition A comprising a safe and effective amount of pine bark extract and grape seed extract together with one or more components acceptable for oral use.
  • composition A comprising a safe and effective amount of pine bark extract and grape seed extract together with one or more components acceptable for oral use.
  • composition comprising:
  • kits to decrease skin hyperpigmentation comprising:
  • percentage by weight also referred to as% by weight, as used herein refers to the percentage of each ingredient of the composition in relation to the total weight.
  • relationship as used herein is understood in the usual sense of the magnitude of relative amounts to each other. Specifically, the ratio of two quantities indicates how many times the first quantity (X) is contained in the second quantity (Y) and is expressed as X: Y.
  • pharmaceutically acceptable refers to excipients or carriers suitable for use in pharmaceutical technology for the preparation of compositions for medical use.
  • acceptable components for oral use refers either to pharmaceutically acceptable excipients and / or carriers or to components acceptable for intake.
  • accepted for intake refers to compounds that are, within the scope of medical judgment, suitable for oral administration without giving rise to toxicity or unwanted side effects.
  • components acceptable for topical use refers either to pharmaceutically acceptable excipients and / or carriers or to components acceptable to be applied to the skin. More specifically, it refers to excipients and / or carriers that are, within the scope of medical judgment, suitable for use in contact with human skin without giving rise to toxicity, incompatibility, instability or an allergic response, among other possibilities. Each excipient, and / or carrier "acceptable for topical use” must also be “acceptable” in the sense of being compatible with the other ingredients in the topical formulation.
  • safe and effective amount refers to the amount of active ingredients in each of the topical and oral compositions that is high enough to produce the desired effect after application, but low enough to avoid side effects at a ratio. reasonable benefit / risk.
  • subject refers to a human, particularly a woman.
  • the present invention relates to the use of a combination comprising pine bark extract and grape seed extract for the preparation of an oral composition A to decrease the hyperpigmentation of the skin in a human, where said composition is administered sequentially or separately. in combination with a topical composition B comprising phenylethylresorcinol, niacinamide and tetrapeptide-30, together with one or more components acceptable for topical use.
  • each of the pharmaceutical compositions comprises one or more pharmaceutically acceptable excipients and / or carriers.
  • Tetrapeptide-30 is a peptide with the amino acid sequence PKEK (proline-lysine-glutamic acid-lysine) that decreases post-inflammatory hyperpigmentation contributing to a homogeneous skin tone. All components of the combination of the invention are commercially available.
  • the combined use of an oral composition A and a topical composition B as defined above provides an improved effect on the depigmentation of the hyperpigmented areas of the skin due to the synergistic action exerted by both compositions.
  • the pine bark extract is French marine pine bark extract (Pinus pinaster, Aitón, Atlantic Villar subsp. ), marketed under the name Pycnogenol® and manufactured by Horphag Research, Geneva, Switzerland. Pycnogenol is standardized to contain 65-75% of proanthocyanidins.
  • the extraction procedure is carried out on the freshly crushed crust and uses ethanol and water in a patented equipment that allows a continuous and automated procedure (Rohdewald P. "A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology "Int J Clin Pharmacol Ther. 2002; 40 (4): 158-168; EP313441).
  • the purified aqueous extract is spray dried to give a fine water soluble brown powder.
  • proanthocyanidins consists mainly of procyanidins (biopolymers of catechin and epicatechin subunits) and phenolic acids (p-hydroxybenzoic acid, protocatechic acid, gallic acid, vanillic acid, caffeic acid, ferulic acid, and p-cumaric acid).
  • Grapeseed extract (Vitis vinifera L.) is also a commercial product that contains 80-90% proanthocyanidins.
  • the extract can be obtained, for example, by the procedure described in Yamaguchi F et al. "Free radical scavenging activity of grape seed extract and antioxidants by electron spin resonance spectrometry in an H 2 02 / NaOH / DMSO system", J. Agrie Food. Chem. Vol. 47, pp. 2544-2548, or that described in Koga T, et al. "Increase of antioxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds” 1999, J. Agrie.
  • the combination of the present invention is effective not only when both oral and topical compositions are administered sequentially, but also when administered separately.
  • oral composition A is administered sequentially with topical composition B.
  • oral composition A is administered separately and in any order with topical composition B.
  • the oral composition of the combination of the invention comprises a safe and effective amount of the active components, pine bark extract and grape seed extract, together with one or more excipients and / or carriers acceptable for intake. Both extracts inhibit melanogenesis or even the proliferation of melanocytes only in the area where the hyperpigmentation problem manifests. Therefore, in a preferred embodiment the decrease in skin hyperpigmentation is achieved by inhibiting melanogenesis or melanocyte proliferation in the area where hyperpigmentation manifests.
  • the topical composition of the combination of the invention comprises a safe and effective amount of the active components phenylethylresorcinol, niacinamide and tetrapeptide-30, together with one or more excipients and / or carriers acceptable for topical use, such as creams, emulsions, fluids, lotions, sprays, and gels, among others.
  • the oral composition of the invention can be formulated in solid and liquid forms.
  • the topical or oral compositions of the present invention can be prepared according to methods known in the state of the art.
  • the oral composition is a solid form, more preferably contained in a gelatin capsule.
  • Solid forms may be prepared by conventional means with pharmaceutically acceptable excipients and / or carriers or components suitable for intake such as emulsifiers, thickeners or viscosity modifiers, anti-caking agents or anti-disintegrants, coating agents and humectants.
  • oral dosage forms suitable for the present invention include forms such as tablets, powders and capsules, among others.
  • Suitable excipients and / or carriers for use in the oral formulations described herein include, but are not limited to the same, diluents such as fillers, binders, lubricants, disintegrants, enhancers of the solubility, colorant, sweeteners and other components commonly used in oral formulations.
  • the excipients used are well tolerated, stable, and used in an appropriate amount to provide the desired consistency and ease of administration.
  • the oral composition A comprises from 3% to 30% by weight of pine bark extract, with respect to the total weight of the oral composition, and from 3 to 30% by weight of extract of grape seed, with respect to the total weight of the oral composition, together with one or more components acceptable for oral use.
  • the combined amount of pine bark extract and grape seed extract in the oral composition of the invention is from 10% to 20% by weight with respect to the total weight of the oral composition, and preferably is of 17.6% by weight with respect to the total weight of the oral composition, the sum of components of the topical composition being 100%.
  • the specific ratio of pine bark extract to grape seed extract in the oral composition is between 10: 1 and 1: 10. In another particular embodiment, the ratio of pine bark extract to grape seed extract is between 3: 1 and 1: 3.
  • Non-limiting examples of appropriate ratios of both components in the oral composition are 2: 1, 1: 1, 1: 2, 1: 3, 1: 4, 1: 5, 1: 10, 3: 4, 3: 5, 4: 5, and 4: 10.
  • the ratio of pine bark extract to grape seed extract in the oral composition is 1: 1.
  • the ratio of both components in the oral composition is 2: 1. Relationships are expressed as weight relationships.
  • the forms of the topical composition for application on the skin can be prepared by conventional means with excipients and / or carriers acceptable for topical use such as emulsifiers, emollients, thickeners or viscosity modifiers, stabilizers, humectants, pH regulators, suspending agents, antioxidants, solubilizers, colorants, perfumes and preservatives.
  • excipients and / or carriers acceptable for topical use such as emulsifiers, emollients, thickeners or viscosity modifiers, stabilizers, humectants, pH regulators, suspending agents, antioxidants, solubilizers, colorants, perfumes and preservatives.
  • topical dosage forms suitable for the present invention include solutions, aerosols, sprays, creams, lotions, gels, ointments, and emulsions, among others.
  • the excipients and / or carriers used are well tolerated, stable, and are used in an appropriate amount
  • the topical composition is a facial fluid.
  • the amount of phenylethylresorcinol in the topical composition of the invention is 0.1 to 4% by weight, and preferably 0.5% by weight, based on the total weight of the topical composition.
  • the amount of niacinamide in the topical composition of the combination of the invention can be comprised between 0.1 -6% by weight, and preferably is 5% by weight, based on the total weight of the topical composition.
  • the amount of tetrapeptide-30 in the topical composition of the combination of the invention is 0.5 to 70 ppm and preferably is 40 ppm.
  • the oral composition of the present invention may further comprise other active ingredients commonly used in compositions for oral use, including, but not limited to, vitamins, such as vitamins C, E and B3 (niacinamide), and selenium, or one of its salts acceptable for intake, such as sodium selenite. Therefore, in a particular embodiment, optionally in combination with one or more characteristics of the various particular or preferred embodiments previously or subsequently defined, the oral composition further comprises vitamin C and vitamin E, preferably vitamin C and vitamin E and niacinamide (vitamin B3 ).
  • composition of the invention further comprises vitamin C, vitamin E and L-cysteine or a precursor thereof, such as N-Acetylcysteine
  • the oral composition further comprises sodium selenite.
  • the oral composition of the combination of the invention comprises or consists of the following components:
  • the oral composition of the combination of the invention comprises or consists of the following components:
  • the topical composition of the present invention may also further comprise other active ingredients commonly used in topical compositions, including, but not limited to, at least one sunscreen agent; N-acetylglucosamine; at least one antioxidant such as vitamin C, derivatives of vitamin C, vitamin E, derivatives of vitamin E, coenzyme Q10 and lipoic acid; at least one retinoid, such as retinol (vitamin A), retinol palmitate, retinol aldehyde, retinol retinoate, tretinoin, isotretinoin, alitretinoin, alpha-14-hydroxy-retro-retinol, fenretinide, polyrenoic acid, etretinate, acitretin, isoacitretin, motretinide , poloprenoic acid, arotinoid ethyl ester, arotinoid carboxylic acid, arotinoid ethyl sulfone
  • adapalene, tazarotene, bexarotene, tamibarotene and mafarotene an alpha-hydroxy acid, such as glycolic acid, lactic acid, malic acid, citric acid, tartaric acid, mandelic acid and benzyl acid, a beta-hydroxy acid, such as salicylic acid, a polyhydroxy acid such as 2-hydroxyoctanoic acid, gluconolactone and glucoheptonolactone, a bionic polyhydroxy acid, such as lactobionic acid and maltobionic acid, and combinations thereof.
  • an alpha-hydroxy acid such as glycolic acid, lactic acid, malic acid, citric acid, tartaric acid, mandelic acid and benzyl acid
  • a beta-hydroxy acid such as salicylic acid
  • a polyhydroxy acid such as 2-hydroxyoctanoic acid, gluconolactone and glucoheptonolactone
  • a bionic polyhydroxy acid such as lactobionic acid and mal
  • the topical composition of the combination of the invention comprises or consists of the following components:
  • one or more components acceptable for topical use preferably at least one emulsifier, an emollient, a humectant and a preservative.
  • the topical composition of the combination of the invention comprises or consists of the following components:
  • one or more components acceptable for topical use preferably at least one emulsifier, an emollient, a humectant and a preservative.
  • the topical composition of the combination of the invention comprises or consists of the following components:
  • the topical composition of the combination of the invention comprises or consists of the following components:
  • one or more components acceptable for topical use preferably at least one emulsifier, an emollient, a humectant and a preservative
  • the amount of phenylethylresorcinol is from 0.1% to 2% by weight with respect to the total weight of the topical composition
  • the amount of niacinamide is 0.5% to 6% by weight with respect to the total weight of the topical composition
  • the amount of tetrapeptide-30 is 0.5 to 50 ppm, the sum of components of the topical composition being 100%.
  • the invention also provides a kit to decrease skin hyperpigmentation.
  • the amount of pine bark extract is from 1% to 30% by weight with respect to the total weight of the oral composition;
  • the amount of grape seed extract is 1% to 30% by weight with with respect to the total weight of the oral composition;
  • the amount of phenylethylresorcinol is 0.1 to 2% by weight with respect to the total weight of the topical composition;
  • the amount of niacinamide is 0.5 to 6% by weight with respect to the total weight of the topical composition;
  • the amount of tetrapeptide-30 is 0.5 to 50 ppm.
  • the different aspects of the invention defined as uses for the preparation of oral or topical compositions to decrease skin hyperpigmentation can also be formulated analogously as therapeutic treatment methods to decrease skin hyperpigmentation in a subject, where The method comprises administering to said subject a safe and effective amount of said oral or topical compositions.
  • the combination of compositions of the invention has an improved effect of decreasing skin hyperpigmentation against known formulations.
  • Hyperpigmentation disorders include melasma (chloasma), post-inflammatory hyperpigmentation, sun lentigo, freckles, age spots (senile lentigo) or, in general, pigmentation spots that appear on the skin after sun exposure often in combination with drugs, such as contraceptives or other hormonal medication, or perfumes, or during pregnancy.
  • the combination of the invention is useful for decreasing skin hyperpigmentation when it manifests as melasma.
  • the oral and topical compositions are administered daily.
  • the oral composition is administered once a day and the topical composition once or several times a day.
  • the topical composition is administered twice daily.
  • both compositions are administered daily for a period of between 3 and 12 months, more preferably for 6 months, more preferably even for 3 months.
  • the combination of the invention comprising a topical composition and an oral composition, as defined above, allows a shorter duration of the combined treatment than would be expected. Therefore, the combined administration of the two compositions provides greater efficacy than the currently available compositions for decreasing skin hyperpigmentation.
  • Example 1 Oral formulation The following composition was prepared in a gelatin capsule (1): Quantity
  • Grape Extract (Vitis vinifera L.) 37.50
  • Vitamin C (Ascorbic Acid) 30
  • Vitamin E 50% (D-alpha tocopherol) 10
  • Vitamin B3 (Nicotinamide) 8
  • the preparation was carried out, first, by mixing and homogenization of the active components (Pycnogenol®, grape extract, vitamin C, 50% vitamin E, vitamin B3, sodium selenite, magnesium stearate and microchstalin cellulose) and later encapsulated in gelatin capsules.
  • active components Pigmentol®, grape extract, vitamin C, 50% vitamin E, vitamin B3, sodium selenite, magnesium stearate and microchstalin cellulose
  • composition of the topical formulation :
  • a fluid emulsion was prepared with the following components:
  • dibutyl adipate cyclopentasiloxane, cyclohexanesiloxane, dimethiconol
  • octocrylene titanium dioxide
  • butylmethoxy dibenzoylmethane bis-ethylhexyloxyphenol methoxyphenyl triazine
  • Phase (00) was heated to 70-80 ° C in the main reactor. Next, the components of Phase (01) on Phase (00) were added one by one and with stirring. Once well dispersed, the components of Phase (02) were added one by one and with stirring. They were stirred until fully incorporated and then the components of Phase (03) were added. Once Phase (03) was well dispersed, Phase (04) was added.
  • Phase (05) The components of Phase (05) were added one by one and with stirring until completely dissolved.
  • Phase (05) On the phases already incorporated in the reactor, the components of Phase (05) were added and the emulsion proceeded. Once the emulsion was obtained, Phase (06) was incorporated with stirring below 40 ° C. Then, below 30 ° C, Phase (07) was added with stirring of blades.
  • the melanin index was measured in the hyperpigmented area and in the area adjacent to it;
  • the MASI Mellasma Area and Severity Index
  • the number of spots and the area of involvement were determined with a visualization system, for example VISIA-CA®, which allowed to calculate the total surface area of the selected hyperpigmented area and, additionally, was performed a visual assessment of the degree of improvement by both the dermatologist and the treated subject.
  • the efficacy test was performed on a population sample of 30 people between 18 and 50 years of age, of all skin types and phototypes, with mild or moderate hyperpigmentation, considered adequate to check acceptability and evaluate the effectiveness of the product. The treatment was maintained for 3 months.
  • composition of example 1 was administered, in another of the groups the composition of example 2 was administered and in the third group both compositions were administered.
  • the oral composition was administered at a dose of two capsules with breakfast with a glass of water.
  • the topical composition was administered twice a day, in the morning and at noon, all over the face by a gentle digital massage until completely absorbed before sun exposure. .
  • the results obtained showed that the combination of the depigmenting oral composition of Example 1 co-administered with the topical composition of example 2 showed that surprisingly the depigmenting effect was visible in more than 80% of people in a shorter period of time than would be expected for such combination.
  • the combination showed a statistically significant depigmenting effect, reducing the number of spots and the area of the spots. A significant decrease in the area of melasma was also observed in a shorter period of time than would be expected for said combination.
  • Yamaguchi F et al. Free radical scavenging activity of grape seed extract and antioxidants by electron spin resonance spectrometry in an

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Abstract

L'invention concerne l'utilisation d'une combinaison comprenant un extrait d'écorce de pin et un extrait de pépin de raisin pour la préparation d'une composition orale destinée à réduire l'hyperpigmentation de la peau, ladite composition étant administrée de manière séquentielle ou séparée en combinaison avec une composition topique qui comprend du phényléthyl-résorcinol, de la niacinamide et du tétrapeptide-30, conjointement avec un ou plusieurs excipients et/ou supports acceptables pour un usage topique. L'invention concerne également une trousse comprenant une composition orale et une composition topique renfermant lesdits constituants.
PCT/ES2014/070362 2013-07-26 2014-04-24 Combinaison pour réduire l'hyperpigmentation de la peau Ceased WO2015011311A1 (fr)

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ESP201331146 2013-07-26
ES201331146A ES2530140B1 (es) 2013-07-26 2013-07-26 Combinación para disminuir la hiperpigmentación de la piel

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CN113827699A (zh) * 2020-06-23 2021-12-24 C·扎维拉 亮肤配方
US12527730B1 (en) * 2025-01-29 2026-01-20 The Procter & Gamble Company Skin care compositions and methods of using the same

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018001485A1 (fr) * 2016-06-30 2018-01-04 Symrise Ag Médicament et composition cosmétique comprenant des dérivés de résorcinol
KR20190025627A (ko) * 2016-06-30 2019-03-11 시므라이즈 아게 레조르시놀 유도체를 포함하는 약제 및 화장품 조성물
JP2019519577A (ja) * 2016-06-30 2019-07-11 シムライズ アーゲー レゾルシノール誘導体を含む医薬及び化粧組成物
US11071701B2 (en) 2016-06-30 2021-07-27 Symrise Ag Medicament and cosmetic composition comprising resorcinol derivatives
JP2021120373A (ja) * 2016-06-30 2021-08-19 シムライズ アーゲー レゾルシノール誘導体を含む医薬及び化粧組成物
JP7177706B2 (ja) 2016-06-30 2022-11-24 シムライズ アーゲー レゾルシノール誘導体を含む医薬及び化粧組成物
KR102667506B1 (ko) 2016-06-30 2024-05-20 시므라이즈 아게 레조르시놀 유도체를 포함하는 약제 및 화장품 조성물
CN113827699A (zh) * 2020-06-23 2021-12-24 C·扎维拉 亮肤配方
US12527730B1 (en) * 2025-01-29 2026-01-20 The Procter & Gamble Company Skin care compositions and methods of using the same

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