JP2012509257A - Topical whitening cosmetic composition and method of use - Google Patents

Abstract

Provided is a topical cosmetic composition that may include a phyllanthus extract, a belith extract, and a licorice (Glyciliza) extract. These compositions are used for topical cosmetic applications, in particular for skin whitening. A method of whitening the skin is also provided and may include topically administering to the skin of a subject in need thereof a therapeutically effective amount of a topical cosmetic composition comprising a philanthus extract, a belith extract, and a licorice extract.

Description

  The invention described herein relates to a topical cosmetic or dermatological composition comprising a plant extract. These compositions are used for topical cosmetic applications, particularly to treat unwanted skin pigmentation.

  Safe and effective topical whitening cosmetic compositions are in particular partly caused by hyperfunctioning melanocytes such as idiopathic melasma (gestational melasma or brown spots) occurring during pregnancy or after estrogen-progesterone contraception Hyperpigmentation, local hyperpigmentation caused by benign melanocyte hyperfunction and proliferation such as senile molasses known as melasma, accidental hyperpigmentation such as photosensitization and scarring after injury, skin irritation When age (eg, aging urine) and damaged skin cannot be recolored, whitening or depigmenting the remaining areas of normal skin to whiten the entire skin to a uniform color, such as vitiligo Desirable for the treatment of unwanted skin pigmentation, including certain forms of leukoplakia.

  Several active ingredients and formulations are currently known that whiten the skin, ie suppress skin pigmentation. These products currently in use contain hydroquinone, but such products have recently been considered unacceptable for toxicological reasons. In fact, RDC 215 has prohibited the use of hydroquinone in cosmetic products since December 2007.

  US Patent Application No. 2008/0050459 includes Phyllanthus Emblica extract, Belis Perrenis extract, Glycyrrhiza Glabra extract, and a combination of small wrinkles and crumbs A cosmetic composition and / or a skin lightening agent is described which requires at least one oligopeptide to achieve its cosmetic effect of the method. Suitable oligopeptides have been described as having a suitable molecular weight that acts as a carrier for the extract of the philanthus embrica and whose effect can penetrate the skin to the maximum extent. The only oligopeptides published to achieve cosmetic compositions are oligopeptide-4 (pro-collagen oligopeptide) and oligopeptide-5 (pro-elastin oligopeptide).

US Patent Application No. 2008/0050459

  There remains a need in the art for improved topical cosmetic compositions containing agents that whiten the skin safely and effectively.

  The present invention relates generally to topical cosmetic compositions useful for treating various skin disorders or conditions associated with undesirable skin pigmentation. Furthermore, the present invention relates to a topical cosmetic composition useful for whitening skin areas where skin deposition is suitable for the skin quality of an individual by makeup.

  In one embodiment, the present invention comprises a topical cosmetic composition comprising, consisting essentially of, or consisting of a Phyllanthus extract, a Bellis extract and a licorice extract. About. In one embodiment, the present invention relates to a topical cosmetic composition comprising, consisting essentially of, or consisting of a philanthus extract, a belith extract and a licorice extract. In one embodiment, the cosmetic composition does not include at least one oligopeptide. In another embodiment, the cosmetic composition does not comprise at least one oligopeptide that is normally absent of a philanthus extract, belis extract or licorice extract. In a further embodiment, the cosmetic composition does not comprise oligopeptide-4 (pro-collagen oligopeptide) and oligopeptide-5 (pro-elastin oligopeptide). In another embodiment, the cosmetic composition does not include an oligopeptide having an appropriate molecular weight that acts as a carrier for at least one Filanthus embrica extract and whose effect can penetrate the skin to the maximum extent.

  In one embodiment, the present invention relates to a topical cosmetic composition comprising, consisting essentially of, or consisting of a Filanthus embryonica extract, a Belis perrennis extract and a licorice extract.

  In another embodiment, the present invention comprises at least one skin lightening active ingredient comprising, consisting essentially of, or consisting of a philanthus extract, a belith extract and a licorice extract. Sunscreens as well as topical cosmetic compositions comprising, consisting essentially of, or consisting of cosmetically acceptable carriers.

  In another embodiment, the present invention comprises a skin lightening active ingredient comprising, consisting essentially of, or consisting of a philanthus embrica extract, a belith perennis extract and a licorice extract, It relates to a topical cosmetic composition comprising, consisting essentially of or consisting of at least one sunscreen, as well as a cosmetically acceptable carrier.

  In one embodiment, the present invention comprises a skin whitening active ingredient comprising, consisting essentially of, or consisting of a philanthus extract, a beris extract and a licorice extract, and at least one of It relates to topical cosmetic compositions comprising, consisting essentially of, or composed of non-skin whitening ingredients including sunscreens.

  In one embodiment, the present invention comprises a skin lightening active ingredient comprising, consisting essentially of, or consisting of a Filanthus embrica extract, a Belis perrennis extract and a licorice extract, and It relates to a topical cosmetic composition comprising, consisting essentially of, or consisting of non-skin whitening ingredients comprising at least one sunscreen.

  In another embodiment, the present invention is a method for whitening skin pigmentation in a subject, wherein a therapeutically effective amount of a topical cosmetic composition according to the present invention as described herein is applied to the skin of the subject in need thereof. It relates to a method comprising topical administration.

  In yet another embodiment, the present invention is a method of treating a skin disorder or condition in a subject, wherein the subject in need thereof has a therapeutically effective amount of a topical cosmetic composition according to the present invention as described herein. It relates to a method comprising topical administration to the skin.

FIG. 2 is a graph showing progressive whitening over time that became statistically significant after 21 days for site B treated with 2% hydroquinone. It is a figure which shows the progressive whitening which became statistically significant after 14 days about the site | part E treated with the topical cosmetic composition of this invention with time. FIG. 5 shows progressive whitening (natural degradation of synthesized melamine) with no significance during the experimental time for an untreated control site (site F). FIG. 5 shows a comparison of the average of colorimeter values between treatments 1 (site B) and 2 (site E) and control (site F) during the evaluation time. Shown are photographs of clinical data supporting colorimetric results in treatments 1 (site B) and 2 (site E) and control (site F) comparing evaluation times T0 and T21.

Definitions As used herein, terms such as “administering”, “administration” and the like are intended in a way that has a positive effect on a dermatological disorder, condition or appearance in a healthy medical or cosmetic act. Means any method of delivering the composition. The composition can be administered so as to cover the entire area to be treated. “Direct administration” means any method of delivering a composition to a subject in a healthy medical or cosmetic practice without the use of another composition, delivery agent, or device. “Indirect administration” means any method of delivering a composition to a subject using at least another composition, delivery agent, or device in sound medical or cosmetic practice.

  As used herein, “aqueous solvent” means a solvent such as water or a solvent containing water. Other dissolved components, such as salts, buffers, and other components understood by those skilled in the art as desired in aqueous solutions, may be present in small amounts.

  “Anhydrous formulation” means any formulation of the topical cosmetic composition of the present invention that does not contain water.

  “Cosmetically acceptable” means a non-toxic, inert, and / or physiologically compatible composition.

  As used herein, the phrase “effective amount” or “therapeutically effective amount” of an active agent or ingredient as defined herein means the amount of active agent sufficient to have a positive effect on the area of application. To do. Therefore, these amounts are sufficient to change the skin disorder, condition or appearance to be treated, within sound medical or dermatological judgment, but not enough to avoid serious side effects Few. A therapeutically effective amount of the active agent provides substantial relief of symptoms when applied repeatedly over time. The effective amount of the active agent will vary with factors such as the particular condition or condition being treated, the severity of the condition, the duration of treatment, the particular components of the composition used.

  As used herein, “extract” means one or more components isolated from a plant material in liquid or powder form. The plant material may comprise or consist of the entire plant or one or more parts of the plant, for example, plant fruits, flowers, roots, leaves, stems and / or bark. The liquid or liquid extract can be dried, eg, spray dried or dried to form a powder. The extract can be a mixture of one or more components of the plant in liquid and / or powder form.

  “Non-skin whitening” includes any compound, substance or composition, or drug, or one or more drugs, substances and compositions that do not depigment or whiten the skin when topically applied to the skin, or The component comprised from them is meant. Such agents are described, for example, as described herein, for example, one or more active agents, such as sunscreens, anti-acne agents, antibacterial agents, anti-wrinkle agents, anti-atrophy agents, anti-inflammatory agents, and Optical brightener and / or one or more cosmetically acceptable excipients, such as thickeners, chelating agents, humectants, emollients, wetting agents, gelling agents, pH adjusting agents, Surfactants, stabilizers, vitamins, penetration enhancers, perfumes, colorants, solvents, and / or combinations thereof may be included.

  As used herein, “pharmaceutically acceptable free base, salt, ester, or solvate” has the same pharmacological activity as the target compound (s) and Means the free base, salt, ester, or solvate of the target compound (s) that is not undesirable in this respect. Salts, esters or solvates can be formed, for example, with organic or inorganic acids. Water or oil-soluble or dispersible products are thereby obtained.

  As used herein, “oligopeptide” means a peptide having an appropriate molecular weight that acts as a carrier for the extract of Filansus Emblica and can penetrate the skin. Oligopeptides that act as a carrier for the extract of Philanthus embrica and can penetrate the skin include oligopeptide-4 (pro-collagen oligopeptide) and oligopeptide-5 (pro-elastin oligopeptide). As used herein, “oligopeptide” does not mean any peptide in which a filanthus extract, beliss extract or licorice extract normally exists. It should be noted that in one embodiment of the present invention, the cosmetic composition does not contain at least one oligopeptide that is normally absent of a phyllanthus extract, beliss extract or licorice extract.

  As used herein, “serum” means a hydrophilic liquid formulation. The serum may optionally be free of one or more emollients, waxes and silicones.

  As used herein, “skin whitening agent” means any compound, substance or composition that whitens or depigments the skin when applied topically to the skin. Such skin lightening agents can include, but are not limited to, pigmentation inhibitors, tyrosinase inhibitors, and melanogenesis inhibitors of melanocytes.

  As used herein, “synergistic skin lightening system” or “synergistic skin lightening component” includes or consists of a Filanthus embrica extract, a belith perennis extract, a licorice extract, each individually The skin whitening active ingredient which shows a synergistic skin whitening effect compared with the skin whitening effect of the skin whitening active agent. In this respect, the combination of these components provides a greater effect than the additive skin whitening effect.

  As used herein, “treatment” or “treating” of a skin disease, disorder, or condition includes alleviating at least one symptom thereof, reducing their severity, or delaying, preventing their progression. Or inhibition is included. Treatment need not imply complete cure of the disease, disorder or condition. The compositions useful herein reduce the severity of a skin disease, disorder or condition, reduce the severity of symptoms associated therewith, improve the patient's quality of life, or skin disease, disorder Or only necessary to delay, prevent or inhibit the onset of the condition.

  As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. pay attention to.

  Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention described herein pertains.

  Where a range of values is provided, e.g., a concentration range, a percentage range, or a ratio range, each intervening value between the upper and lower limits of the range is the lower limit unless the context clearly dictates otherwise. It is understood that up to one-tenth of a unit and other specified values or specified intervening values within the specified range are included within the scope of the described invention. The upper and lower limits of these smaller ranges may be independently included in the smaller ranges, and such embodiments are also described according to any specifically excluded limits within the specified ranges. Included within the scope of the present invention. Where the specified range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the described invention.

  Throughout the application, the description of various embodiments uses the phrase “comprising”, but in some specific cases, embodiments may alternatively be “consisting essentially of” or One skilled in the art will appreciate that the description can be described using the phrase “consisting of”.

  In order to better understand the teachings of the present invention and not to limit the scope of the teachings in any way, all of the numbers, proportions or ratios used in the specification and claims, and others, unless otherwise stated It should be understood that in each case the number is modified by the term “about”. Accordingly, unless stated to the contrary, the numerical parameters set forth in the following specification and appended claims are approximations that can vary depending upon the desired properties sought to be obtained. At a minimum, each numeric parameter should be interpreted by applying the usual rounding method, taking into account at least the reported number of significant digits.

The present invention relates to a topical cosmetic composition comprising, consisting essentially of, or consisting of a philanthus extract, a belith extract and a licorice extract.

Main skin lightening actives According to the invention described herein, the topical cosmetic composition of the invention comprises a phyllanthus extract, ie, a philanthus embrica extract, a belith extract, ie, a belis perrennis extract. And licorice extract or may consist of them.

  “Philanthus extract” refers to, for example, Phyllantus embilica, Phyllantus niruuri L. , Phyllantus elegans Wall, Phyllantus iniruri, Phyllantus reticulatus, Phyllantus urinaria L. , Phyllantus reticulatus Poir, Phyllantus conami Sw, Phyllantus lathyroides H. et al. B. K. Means an extract obtained from a group of fruits of the genus Philanthus including Phyllanthus casticum Soy-Will and Phyllanthus medagascariensis. Filanthus extract is a safe and effective natural antioxidant.

  “Filans Emblica extract” includes, for example, a standardized extract of Philanthus Emblica, including EMBLICA® (a branch of Merck KGaA, Darmstadt, Germany and EM industries, Inc., USA, Merck KGaA). means. Philanthus Emblica, also commonly known as “Embilica officinalis Gaertn”, is a member of the family “Euphorbiaceae”. Philanthus Emblica is a very rich source of vitamin C and has an ascorbic acid content in the range of 1000-1800 mg per 100 grams of fruit. Philanthus Emblica extract is a safe and effective natural antioxidant that has no oxidation-inducing activity and can exhibit bifunctionality, ie chelation and antioxidant. Unlike most antioxidants that go from active form to inactive form, the extract of Philanthus embrica can exhibit a cascade effect that provides stable antioxidant activity that lasts for a long time. The Filansas Emblica extract is produced by extracting high quality fruit using a water based process as described in US Pat. No. 6,124,268, which is incorporated herein by reference in its entirety. Can do. Philanthus embrica extracts generally contain low molecular weight tannins, so-called embricanin A and embricanin B, together with pedunclazine and punygluconin, rutin and gallo-elagitanoid.

  “Bellis extract” includes, for example, an extract obtained from a flower of a member of the genus Beris, for example, a flower of Belis Perennis and / or a flower of Belis rotundifolia L. It means an extract obtained from a group of genus Belis. The Belis extract may contain or consist of one or more bioactive molecules including saponins (triterpene glycosides), polyphenols (phenolic acid), flavonoid glycosides, polysaccharides and inulins.

  A “Beris Perennis extract” comprises or is composed of one or more bioactive molecules including saponins (triterpene glycosides), polyphenols (phenolic acid), flavonoid glycosides, polysaccharides and inulins. It means an extract obtained from Perennis flowers. A suitable Belis Perennis extract may include BELIDES® available from CLR Chemisches Laboratorium, Berlin, Germany. Bellis perennis is also described in Bellis alpina Hegetschw. Bellis hortensis Mill. Bellis hybrida Ten. Bellis integrifolia DC. And commonly known as Bellis scaposa Gilib.

  A “licorice extract” means an extract obtained from a group of genus Glycyrrhiza, for example, from a group of roots of the genus Glycyrrhiza. The genus “Glyciliza” is a member of the “Fabaceae” family. Suitable glycyrrhisa extracts can include oil-soluble licorice extracts available from Bioland, Korea. Other suitable glycyrrhaza extracts are available from Glycyrrhiza echinata L. (Chinese licorice), Glycyrrhiza glabra L. et al. (Cultivated licorice), Glycyrrhiza lepidota L. Glycyrrhiza glutinosa, polypodium Glycyrrhiza, Glycyrrhiza brachycarpa Boiss. Glycyrrhiza germanica Tourn. Glycyrrhiza grandilifera Waldst. et Kit. Glycyrrhiza hirsuta L .; Glycyrrhiza laevis Pall. Glycyrrhiza offcinalis Lepech. Glycyrrhiza pallida Boys. Glycyrrhiza siliqosa Tour. Glycyrrhiza violacea Boys. Glycyrrhiza viscose Turcz. ex Ledeb. Glycyrrhiza vulgaris Gueldenst. It can be obtained from one or more of a group of Glycilizae, including ex Ledeb, Liquiritia officinalis Moench and Liquiritia officinalum Medik.

  In one embodiment, the topical cosmetic composition of the present invention may comprise or consist of a skin lightening active ingredient that may comprise or consist of a philanthus extract, a beris extract and a licorice extract.

  In one embodiment, the topical cosmetic composition of the present invention comprises or consists of a skin lightening active ingredient that may comprise or consist of a Filanthus embrica extract, a belith perennis extract and a licorice extract. Can be configured.

  In one embodiment, the present invention provides that the topical skin lightening active ingredient is from about 0.5% to about 43%, from about 1% to about 30%, about 1.5% by weight based on the total weight of the composition. To about 23%, about 1.5% to about 15%, about 3% to about 10%, about 6% to about 8%, or about 7.05% by weight The present invention relates to a topical cosmetic composition present in a cosmetic composition.

  In another embodiment, the present invention relates to a phyllanthus extract, for example, a philanthus embrica extract, from about 0.1% to about 8%, from about 0.25% to about 4%, based on the total weight of the composition. In a topical cosmetic composition in an amount of about 0.5%, about 0.5% to about 3%, about 0.5% to about 2%, about 1% to about 2% or about 2% by weight. The present invention relates to a topical cosmetic composition.

  In other embodiments, the present invention provides a belis extract, such as a belis perennis extract, from about 0.5% to about 30%, from about 1% to about 20% by weight, based on the total weight of the composition. Topical cosmetic composition present in an amount of about 2% to about 10%, about 3% to about 7%, about 4% to about 6% or about 0.5% by weight The present invention relates to a cosmetic composition.

  In yet another embodiment, the invention provides that the licorice extract is about 0.005% to about 5%, about 0.01% to about 2%, about 0.01%, based on the total weight of the composition. In a topical cosmetic composition in an amount of from wt% to about 1 wt%, from about 0.02 wt% to about 0.08 wt%, from about 0.03 wt% to about 0.07 wt% or about 0.05 wt% The present invention relates to a topical cosmetic composition.

  In another embodiment, the present invention provides a phyllanthus extract, such as a philanthus embrica extract, present in a topical cosmetic composition in an amount of about 0.50 wt% to about 2 wt%, A topical cosmetic wherein the perennial extract is present in the topical cosmetic composition in an amount of about 1 wt% to about 20 wt% and the licorice extract is present in the topical cosmetic composition in an amount of about 0.01 wt% to about 1 wt%. Relates to the composition.

  In yet another embodiment, the present invention relates to a licorice extract wherein the philanthus embrica extract is present in the topical cosmetic composition in an amount of about 2 wt%, the belith perennis extract is present in an amount of about 5 wt%. The topical cosmetic composition wherein the product is present in the topical cosmetic composition in an amount of about 0.05 wt%.

  In one embodiment, the present invention comprises or consists essentially of a philanthus extract, such as a philanthus embrica extract, a belis extract, such as a belis perennis extract, and a licorice extract. A topical cosmetic composition comprising, consisting essentially of, or consisting of, a skin-whitening active ingredient, or composed thereof, at least one sunscreen, and a cosmetically acceptable carrier About. A cosmetically acceptable carrier may comprise or consist of one or more cosmetically acceptable excipients.

  In another embodiment, the present invention comprises or consists essentially of a philanthus extract, such as a philanthus embrica extract, a belis extract, such as a belis perennis extract, and a licorice extract. It relates to a topical cosmetic composition comprising, consisting essentially of, or consisting of a skin whitening active ingredient and a non-skin whitening ingredient. Does the non-skin whitening component include one or more active agents, such as sunscreens, cosmetically acceptable carriers, and / or cosmetically acceptable excipients as described herein? Or may consist of them.

  In other embodiments, the present invention relates to a topical cosmetic composition according to the present invention as described herein, which may comprise one or more non-skin whitening active ingredients.

  In yet another embodiment, the topical cosmetic composition and / or the cosmetically acceptable carrier and / or the one or more cosmetically acceptable excipients are a philanthus extract, such as a filanthus extract extract, It can be free of any skin lightening agents other than Belis extract, such as Belis Perennis extract and Licorice extract. A topical cosmetic composition and / or a cosmetically acceptable carrier and / or one or more cosmetically acceptable excipients may be a phyllanthus extract, such as a philanthus embrica extract, a belis extract, such as a belis -It can be free of any plant-derived skin lightening agent other than Perennis extract and Licorice extract. The topical cosmetic composition and / or the cosmetically acceptable carrier and / or one or more cosmetically acceptable excipients can be free of any non-vegetable skin lightening agent.

  In one embodiment, the present invention provides that the composition and / or skin whitening active ingredient and / or non-skin whitening ingredient does not contain hydroquinone or a derivative thereof and / or does not contain a polyorganosiloxane-containing epsilon-polylysine compound, and It relates to a topical cosmetic composition which does not contain flavans.

Synergistic skin lightening ingredients In another embodiment, the present invention comprises or consists essentially of a philanthus extract, such as a philanthus embrica extract, a belis extract, such as a belis perennis extract, and a licorice extract. Synergistic skin lightening active ingredients comprising or consisting of them, wherein the synergistic skin whitening active ingredient is the skin whitening effect of each individual skin whitening active ingredient The present invention relates to a topical cosmetic composition that exhibits a synergistic skin whitening effect.

  In one embodiment, the present invention comprises or consists essentially of a philanthus extract, such as a philanthus embrica extract, a belis extract, such as a belis perennis extract, and a licorice extract. Or a synergistic skin lightening ingredient for use in topical cosmetic compositions composed thereof.

  In another embodiment, the present invention comprises or consists essentially of a philanthus extract, such as a philanthus embrica extract, a belis extract, such as a belis perennis extract, and a licorice extract. Or a synergistic skin lightening component for use in a topical cosmetic composition composed thereof, wherein the synergistic skin whitening component exhibits enhanced skin whitening effect. The synergistic skin lightening component can be free of hydroquinone.

  In one embodiment, the topical cosmetic composition according to the invention described herein may comprise or consist of a skin lightening active ingredient that exhibits a synergistic skin lightening effect.

  In other embodiments, the topical cosmetic composition according to the invention described herein may comprise or consist of a skin lightening active ingredient that exhibits a synergistic skin lightening effect, wherein the topical cosmetic composition comprises hydroquinone. Not included.

  In one embodiment, the topical cosmetic composition or synergistic skin lightening system according to the present invention as described herein may comprise or consist of a skin lightening active ingredient that exhibits a synergistic skin lightening effect, and is a topical cosmetic. The composition is free of hydroquinone and / or flavan and / or polyorganosiloxane-containing epsilon-polylysine compounds.

Cosmetically acceptable carriers Any non-toxic, inert and effective topical cosmetically acceptable carrier can be used to formulate the compositions described herein. Well known carriers used to formulate other topical therapeutic compositions for administration to humans are useful for these compositions. Examples of these ingredients well known to those skilled in the art are described in The Merck Index, 13th edition, edited by Budavari et al., Merck & Co., the entire contents of which are hereby incorporated by reference. , Inc. Rahway, N .; J. et al. (2001); the CTFA (Cosmetic, Toiletry, and Fragrance Association) International Cosmetic Indigenous Dictionary and Handbook, 10th edition (2004); and “Inactive Ingredient Guide”. S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) Office of Management, January 1996. Examples of such useful cosmetically acceptable excipients, carriers and diluents include those suitable for use herein in distilled water, physiological saline, Ringer's solution, dextrose solution, Hanks solution and DMSO are included.

  These additional other inactive ingredients as well as effective formulation and administration methods are well known in the art, both of which are hereby incorporated by reference. Goodman and Gilman's: The Pharmacologic Bases of Therapeutics, 8th edition, edited by Gilman et al., Pergamon Press (1990) and Remington's Pharmaceutical Sciences, 17th edition, Mack Publishing Co. Easton, Pa. (1990).

Sunscreen In another embodiment, the present invention relates to a topical cosmetic composition that may comprise at least one sunscreen. The at least one sunscreen is in an amount of about 0.5% to about 30%, about 1% to about 20%, or about 1% to about 10% by weight based on the total weight of the composition. Can exist.

  Suitable sunscreens may include a broad spectrum sunscreen that protects against both UVA and UVB radiation or a sunscreen that protects against UVA or UVB radiation.

  In one embodiment, the topical cosmetic composition of the present invention comprises methylene bisbenzotriazolyl tetramethylphenol, diethylaminohydroxybenzoyl hexyl benzoate, coated zinc oxide, ethyl hexyl methoxycinnamate, isoamyl methoxycinnamate, homosalate salicylic acid. Sunscreens comprising or consisting of one or more of ethylhexyl, octocrylene, polysilicone-15, butylmethoxydibenzoylmethane, menthyl anthranilate and ethylhexyldimethyl PABA may be included.

  In a further embodiment, the topical cosmetic composition of the present invention comprises one or more of methylene bis-benzotriazolyl tetramethylphenol (TINOSORB M available from CIBA), diethylaminohydroxybenzoyl hexyl benzoate and coated zinc oxide. Sunscreens may be included, including in an amount of about 1% to about 20%, about 2% to about 10%, or about 5% by weight based on the total weight of the composition. For example, the topical cosmetic composition of the present invention comprises methylene bis-benzotriazolyl tetramethylphenol from about 1% to about 20%, from about 2% to about 10%, or from about 1% by weight based on the total weight of the composition. Sunscreens can be included in an amount of 5% by weight or composed thereof.

  In other embodiments, the topical cosmetic composition of the present invention comprises ethylhexyl methoxycinnamate (available from BASF), isoamyl methoxycinnamate, ethylhexyl homosalate salicylate, octocrylene, polysilicone-15, butylmethoxydibenzoylmethane, One or more of menthyl anthranilate and ethylhexyl dimethyl PABA in an amount of about 1% to about 10%, about 5% to about 9%, or about 7.5% by weight, based on the total weight of the composition. Sunscreens comprising or consisting of them may be included.

  In one embodiment, the topical cosmetic composition of the present invention comprises from about 0.5% to about 30%, from about 1% to about 20% by weight of one or more sunscreens, based on the total weight of the composition. Or about 1% to about 10% by weight.

  In one embodiment, the at least one sunscreen is a first sunscreen selected from the group consisting of methylene bisbenzotriazolyl tetramethylphenol, diethylaminohydroxybenzoyl hexyl benzoate, coated zinc oxide, and methoxy cinnamon. A second sunscreen selected from the group consisting of ethyl hexyl, isoamyl methoxycinnamate, ethyl hexyl homosalate salicylate, octocrylene, polysilicone-15, butylmethoxydibenzoylmethane, menthyl anthranilate and ethylhexyl dimethyl PABA, Or they can be composed of them. The first sunscreen is present in an amount of about 1% to about 20% by weight, and the second sunscreen is in an amount of about 1% to about 10% by weight, based on the total weight of the topical cosmetic composition. Can exist. The first sunscreen may comprise or consist of methylene bis-benzotriazolyl tetramethylphenol, and the second sunscreen may comprise or consist of ethylhexyl methoxycinnamate.

  In one embodiment, the invention provides an SPF greater than about 10, SPF greater than about 15, SPF at least about 15, SPF about 15, SPF about 10 to about 45, SPF about 15 to about 45, Or a topical cosmetic composition having an SPF of about 15 to about 25.

Aqueous Solvent The topical cosmetic composition of the present invention may further comprise an aqueous solvent. In one embodiment, the composition of the present invention comprises an aqueous solvent, such as water, from about 5% to about 95%, from about 10% to about 90%, about 25% by weight, based on the total weight of the composition. To about 80%, about 55% to about 75%, about 60% to about 70% or about 63% by weight.

Cosmetically acceptable excipients In yet another embodiment, the present invention relates to a topical cosmetic composition that may comprise water and at least one cosmetically acceptable excipient. Suitable cosmetically acceptable excipients include those commonly known to those skilled in the art to be useful in topical compositions.

In one embodiment, the at least one cosmetically acceptable excipient is an antioxidant, chelating agent, pH adjusting agent, emollient, thickener, gelling agent, free radical scavenger, preservative. , Emulsifiers, wetting agents, humectants, suspending agents, surfactants, stabilizers, vitamins, penetration enhancers, perfumes or fragrances, colorants, liquid alkyl alcohols, polysiloxanes, modified polysiloxanes and combinations thereof It can comprise or consist of one or more components selected from the group.
Topical formulations In one embodiment, the topical cosmetic composition of the present invention comprises a serum, gel cream, lotion, cream, ointment, gel, aerosol, foam, foaming liquid, solution (solubilizing system), paste, suspension. Suspension, dispersion, emulsion, skin cleanser, milk, mask, solid bar, bar (eg bar soap), encapsulated formulation, microencapsulated formulation, microparticle or nanoparticle or vesicle dispersion, or other Formulated into a cosmetically acceptable topical dosage form. In the case of a vesicle dispersion, the lipids forming the vesicles may be ionic or non-ionic or mixtures thereof. Formulations can include one or more aqueous and / or anhydrous formulations.

  In another embodiment, the inventive topical cosmetic composition according to the invention described herein may comprise or consist of an anhydrous formulation, an aqueous formulation or an emulsion.

  In yet another embodiment, the inventive topical cosmetic composition according to the invention described herein is formulated in a serum or gel cream.

Optional additional active agents The topical cosmetic compositions described herein may optionally further comprise one or more cosmetic or dermatological active agents in addition to the described skin lightening actives. Such agents include, for example, additional skin lightening actives including plant-derived and non-plant-derived skin lightening agents such as pigmentation inhibitors, tyrosinase inhibitors, and / or melanogenesis inhibitors of melanocytes. And / or non-skin whitening actives such as fluorescent whitening agents, sunscreens, anti-inflammatory agents, antibacterial agents, antifungal agents, anti-wrinkle agents, anti-atrophy agents, anti-acne agents, free radical scavengers, keratins Solubilizers, vitamins, anti-elastase and / or anti-collagenase agents, peptides, fatty acid derivatives, steroids, trace elements, algae and / or plankton extracts, enzymes and / or coenzymes, flavonoids and / or ceramides, α-hydroxy acids As well as combinations thereof.

Treatment method
In one embodiment, the present invention relates to a method of treating a subject's skin comprising topically administering to the skin of a subject in need thereof a therapeutically effective amount of a topical cosmetic composition according to the present invention as described herein. .

  In one embodiment, the present invention whitens skin pigmentation in a subject comprising topically administering to the skin of the subject in need thereof a therapeutically effective amount of a topical cosmetic composition according to the present invention as described herein. Regarding the method.

  In another embodiment, the present invention provides a skin disorder or condition of a subject comprising topically administering to the skin of a subject in need thereof a therapeutically effective amount of a topical cosmetic composition according to the present invention as described herein. It relates to the treatment method. The skin disorder or condition can be a disorder or condition associated with undesirable skin pigmentation.

  In another embodiment, the present invention provides a therapeutically effective amount of a topical cosmetic composition according to the present invention as described herein at least once per day for at least 3 days, at least 5 days, to the skin of a subject in need thereof. Or a method of whitening skin pigmentation in a subject or treating a skin disorder or condition in a subject comprising topical administration for at least 7 days. In this regard, the skin after 3 days, 5 days, or 7 days after administration of the topical composition of the present invention to the skin is visibly changed.

  In one embodiment, the invention comprises topically administering a therapeutically effective amount of a topical cosmetic composition according to the invention as described herein to the skin of a subject in need thereof at least once per day for at least 3 weeks. The present invention relates to a method of whitening skin pigmentation of a subject or a method of treating a skin disorder or condition of a subject, wherein the skin is visibly whitened after 3 weeks.

  The topical cosmetic compositions of the present invention are effective in treating various skin disorders or conditions characterized by undesirable skin pigmentation. Non-limiting examples of such disorders and / or conditions include parts caused by hyperfunctioning melanocytes such as idiopathic melasma (gestational melasma or brown spots) occurring during pregnancy or after estrogen-progesterone contraception Hyperpigmentation, local hyperpigmentation caused by benign melanocyte hyperfunction and proliferation such as senile mole known as melasma, accidental hyperpigmentation such as photosensitization and scarring after injury, freckles Certain forms, such as vitiligo, whitening or depigmenting the remaining areas of normal skin to give a uniform color throughout the skin, when pigmentation disorders, and damaged skin cannot be recolored May include vitiligo. The skin is not desired for pigmentation, but can be treated by the methods described herein for pure cosmetic whitening of areas of the skin that are suitable for the individual's skin type, eg, large areas. In one embodiment, the skin disorder or condition treated by the methods of the present invention is undesirable skin pigmentation. Administration of the topical cosmetic compositions of the present invention to areas of skin containing undesirable pigmentation will whiten those areas. Thus, the method of the present invention whitens the area of skin to which the topical cosmetic composition of the present invention has been administered.

  Skin areas suitable for treatment and / or whitening according to the invention described herein may include, for example, thin skin areas, including areas of the face, neck and / or hand skin. The compositions and methods of the present invention described herein are suitable for use in both men and women and are suitable for use on all skin types, including dry skin types, normal skin types, and oily skin types.

  In other embodiments, the present invention is a method of treating a skin disorder or condition in a subject, or a method of whitening skin pigmentation in a subject, wherein topical administration to the skin is at least once per day or at least twice per day. A method wherein skin pigmentation is whitened, comprising administering for at least 2 weeks, at least 3 weeks or at least 4 weeks.

Methods of Manufacture Various formulations of the topical cosmetic compositions of the invention according to the invention described herein include such formulations, including, for example, creams, gels, serums, lotions or other formulations described herein. It can be easily manufactured by those skilled in the art without undue experimentation by a known method of manufacturing.

  The manufacturing process of the cream or emulsion formulation may involve preparing the aqueous phase and the oil phase separately, for example adding the oil phase to the aqueous phase while mixing and / or homogenizing (at high shear) to make an emulsion. . After the emulsion is formed, the following ingredients, one or more pH adjusters, one or more emollients, one or more skin lightening actives, one or more sunscreen actives, One or more of one or more thickeners, one or more antioxidants and one or more perfumes are optionally added to them in the following order, for example, to give the final emulsion or cream Can be manufactured. Prior to forming the emulsion, the aqueous and oil phases may be separately heated to a temperature of about 70 ° C to about 99 ° C, about 75 ° C to about 95 ° C, about 80 ° C to about 90 ° C, or about 85 ° C. After heating, the oil phase can be slowly added to the aqueous phase, for example with mixing or high shear homogenization. The resulting emulsion is then maintained at, for example, about 47 ° C to about 27 ° C, about 42 ° C to about 30 ° C, about 39 ° C to about 35 ° C, or about 37 ° C while maintaining mixing and high shear homogenization. Can be cooled to temperature. Thereafter, one or more of the optional ingredients described above can then be added to the cooled emulsion, for example, with mixing and / or high shear homogenization. The resulting emulsion or cream may have a pH of about 4.5 to about 6.5 and / or a viscosity of about 5000 cP to about 15000 cP and / or a density of about 1.01 to about 1.06. .

  Furthermore, the scope of the present invention contemplates topical cosmetic compositions made according to the foregoing process. If produced by these processes, these compositions exhibit chemical and physical stability suitable for topical administration.

  The topical cosmetic composition produced by these processes is a product contact surface comprising a material selected from the group consisting of glass, plastic, steel, stainless steel, aluminum, Teflon, polymer structure, ceramic structure, alloy and mixtures thereof. Can be placed in a suitable closed container containing These sealed containers are used to facilitate the manufacture, handling, processing, packaging, storage and administration of the topical cosmetic composition. Suitable sealed containers in this regard may be selected from the group consisting of plastic tubes, bottles, metal tubes and any combination thereof.

Route of Administration / Dosage To be effective, the route of administration of the topical cosmetic composition used in the method of the present invention must readily affect the target skin area. In most cases, effective results are achieved by applying a thin layer locally to the affected area or areas where it is desired to achieve the desired effect. Effective results can be achieved with a coating rate from once applied every two or three days to four or more times per day.

  Appropriate dosage levels of active agents contemplated in the topical cosmetic compositions and methods of the present invention are well known to those skilled in the art and are selected to maximize the treatment of the aforementioned skin conditions. Dosage levels on the scale of about 0.001 mg to about 5000 mg of skin lightening active ingredient per kilogram body weight are known to be useful in the treatment of the diseases, disorders and conditions contemplated herein. Generally, this effective amount of skin lightening active ingredient generally comprises from about 0.001 mg to about 100 mg per kilogram of patient body weight per day. In addition, it is to be understood that this dosage component can be administered in one or more dosage units to provide the desired therapeutic effect.

  If desired, other therapeutic agents can be used in combination with those listed above for the composition. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host treated, the nature of the disease, disorder or condition and the nature of the active ingredient.

  The compositions of the invention can be administered daily in single or multiple doses. In one embodiment, the topical cosmetic composition of the present invention is administered 1 to 4 times daily. If necessary, one plan is to start once or twice daily at low doses and slowly increase to higher doses. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host treated, the nature of the disease, disorder or condition and the nature of the active ingredient. In one embodiment, the topical cosmetic composition can be topically applied one or more times per day. In one embodiment, the topical cosmetic composition of the present invention is topically applied 1 to 4 times daily. For example, one plan is to start once daily and increase to more frequent application if necessary.

  In one embodiment, the topical cosmetic composition of the present invention is topically applied 1 to 4 times daily, for example, in the morning, noon, afternoon, and / or night.

  In one embodiment, the topical cosmetic compositions described herein can be administered one or more times per day, at least 1 week, at least 2 weeks, at least 4 weeks, or at least 8 weeks. The topical cosmetic composition can be administered one or more times per day, up to 1 year, up to 6 months, up to 3 months or up to 2 months.

  However, the specific dose level for any specific patient is the activity of the specific active agent, the patient's age, weight, general health, sex and diet, administration time, excretion rate, possible concomitant medications It will be appreciated that it will vary depending on a variety of factors, including the severity of the particular condition being treated and the mode of administration. One skilled in the art will understand the variety of such factors and will be able to establish a particular dose level using only routine experimentation.

  Pharmacological parameters such as bioavailability, absorption rate constant, apparent distribution, unbound fraction, total clearance, fraction excreted unchanged, first-pass metabolism, elimination rate constant, halved The period and average residence time are well known in the art.

  The optimal cosmetic formulation can be determined by one skilled in the art depending on considerations such as the particular ingredients and the desired dosage. For example, Remington's Pharmaceutical Sciences, 18th edition (1990, Mack Publishing Co., Easton, PA 18042) 1435-1712 and “Harry's Cosmeticology, the entire disclosures of which are hereby incorporated by reference. ", 8th edition (2000, Chemical Publishing Co., Inc., New York, NY 10016). Such formulations can affect the general condition, stability, release rate in vivo and clearance rate in vivo.

  In one embodiment, the topical cosmetic composition of the invention according to the invention described herein is for example a gel cream encapsulated in a tube or a serum encapsulated in a non-aerosol non-foaming pump container or bottle, for example. The amount of the composition contained in the container can be in the range of about 10 gm to about 60 gm, between about 20 gm and about 50 gm, or about 30 gm, or about 40 gm.

  Single dose kits and packages containing a single dose of composition per day can be prepared. Single doses, unit doses and once daily disposable containers of the compositions of the invention are contemplated as within the scope of the invention.

  The topical cosmetic compositions of the invention according to the invention described herein can be formulated for storage in a substantially non-reactive laminated package in order to increase the stability of the package. This storage method exhibits enhanced packaging stability compared to other paper-based packaging.

  The amount of composition per single package can be between about 0.1 ml to about 20.0 ml, between about 0.5 ml and about 5.0 ml, or between about 1 ml and about 3 ml.

  In particular, the ability to formulate compositions that can be pre-mixed prior to application or stored for long periods without the need for compounding is also contemplated. Specifically, the compositions of the present invention can be between about 3 months and about 3 years, between about 3 months and about 2.5 years, between about 3 months and about 2 years, about 3 months and about 20 months. Maintains unexpected stability during storage for a period of between, or any period between about 6 and about 18 months.

  In one embodiment, the topical cosmetic formulations described herein according to the invention described herein remain stable for at least 3 years at a temperature of less than 30 ° C. In one embodiment, the topical cosmetic formulations described herein remain stable for at least 2 years at a temperature of 30 ° C. or lower. In one embodiment, the topical cosmetic formulations described herein remain stable for at least 2 years at a temperature of 25 ° C. or lower.

  The following examples illustrate the topical cosmetic compositions of the present invention and are not meant to be limiting thereto. Any polymer molecular weight is an average of the average molecular weight. Unless otherwise noted, all percentages are based on the weight percent of the final delivery system or prepared formulation, and the total is all equal to 100% by weight.

Example 1
The following examples illustrate the apparent effectiveness of the topical cosmetic compositions of the present invention compared to a 2% hydroquinone composition as measured by the colorimetric instrument method.

  In a single-center, double-blind, comparative clinical trial over a 6 week period, the apparent effectiveness of each of the two topical products was evaluated on the already pigmented skin of 10 volunteers. Dermatological evaluation was performed at the start and end of the study. Skin color was measured by a colorimeter with photographic records at T0, T07, T14 and T21. UVB pigmentation was induced in the volunteer's already pigmented skin using a solar simulator equipped with a light source, ie, a xenon arc lamp 601 / 300W manufactured by Solar Light CO.

Skin coloration was measured using a Minolta color difference meter CR400 (The Commission International de I'Eclairage) with standard color system CIE. The color is represented by a three-dimensional coordinate system in which the L ^* axis corresponds to skin lightness, the a ^* axis corresponds to green and red, and the b ^* axis corresponds to blue and yellow.

  A solar simulator equipped with a xenon arc lamp 601 / 300W manufactured by Solar Light CO was used as the light source. This device provides continuous light emission in the UVB and UVA spectra in the range of 290 and 400 nm. The device includes a series of lenses and a filter that absorbs or disperses radiation below 320 nm or above 400 nm. Irradiation is performed from six branched optical fibers called “ports” that are set to apply pre-established individual doses. Irradiation monitoring was performed using a dose control system (DCS) including a UVB irradiation detector and an electronic monitor. In this test, only three “ports” were used at each application site of the test composition.

Evaluation sample

Formulation production method Disperse methylene bis-benzotriazolyl tetramethylphenol in a small amount of purified water in a suitable container. Mix until uniform.
2. In a suitable container, blend until the cyclopentasiloxane PEG / PPG-18 / 18 dimethicone and cyclopentasiloxane dimethicone crosspolymer are uniform.
3. Place polyethylene glycol in a suitable container. Add licorice extract and disperse. Mix until uniform.
4). Disperse the fruit extract of Filanthus embrica in a small amount of purified water in a suitable container. Mix until uniform.
5). Disperse triethanolamine in a small amount of purified water in a suitable container. Mix until uniform.
6). Disperse sodium metabisulfite in a small amount of purified water in a suitable container. Mix until uniform.
7). Add the remaining purified water while mixing to the main production vessel and disperse the sodium edetate. Heat the contents to about 85 ° C.
8). To a suitable container, add cetyl alcohol, C _14-22 alcohol and C _12-20 alkyl glycoside, cetyl alcohol, ethylhexyl methoxycinnamate and butylated hydroxytoluene. Heat to about 85 ° C. and mix until uniform.
9. Add the Step 8 mixture to the Step 7 mixture with stirring. Mix until uniform.
10. Cool the batch to about 37 ° C. while mixing.
11. Add the mixture of step 4 and step 5 while mixing. Mix until uniform.
12 Add phenoxyethanol and methylisothiazolinone with mixing.
13. While mixing, add the mixture of step 2 and then the mixture of step 3. Mix until uniform.
14 Add Belis Perennis flower extract and mix until uniform.
15. While mixing, add the mixture from step 1 and mix until uniform.
16. Add hydroxyethyl acrylate, sodium acryloyldimethyltaurate copolymer, squalene and polysorbate 60. Mix until uniform.
17. Add the mixture from step 6 while mixing. Mix until uniform.
18. Add perfume while mixing. Mix until uniform.
19. This formulation has a viscosity in the range of 5,000 to 15,000 cP and a density in the range of 1.01 to 1.06.

Alternative Method of Manufacturing Another Composition This alternative method achieved a change in formulation pH from a pH in the range of 4.0-6.5 to a pH in the range of 5.0-6.5. Licorice extract, Belis Perennis extract and Emblica were generally kept exposed to yellow light and / or protected from exposure to white light. In one embodiment, the entire process, including packaging, preferably occurs under yellow light. In another embodiment, the resulting formulation is stored without exposure to white light and air.

Premix 1. Premix A: In an additional appropriate container, Tinosorb M® (methylenebis-benzotriazolyltetramethylphenol (and) decylglucoside (and) xanthan gum (and) propylene glycol (and) water and second purification Water). Stir until dispersed throughout. Hold.
2. Premix B: Add DC9040® (dimethicone crosspolymer (and) cyclomethicone) and DC5225C® (cyclopentasiloxane / PEG / PPG-18 / 18 dimethicone) to an additional suitable container. Stir until dispersed throughout. Hold.
3. Premix C: Add propylene glycol and licorice extract to an additional appropriate container. Stir until dispersed throughout. Hold.
4). Premix D: Add Emblica and third purified water to an additional appropriate container. Stir until dispersed throughout. Hold.
5). Premix E: Add triethanolamine 99W and 4th purified water to an additional appropriate container. Stir until dispersed throughout. Hold.
6). Premix F: Add sodium metabisulfite and fifth purified water to an additional appropriate container. Stir until dispersed throughout. Hold.

6. Preparation of oil phase In a suitable container, an oil phase is prepared by adding cetyl alcohol, Montanov L® (C14 / C22 alcohol C12 / C20 alkyl glucoside), ethylhexyl methoxycinnamate and butylated hydroxytoluene. Heat to 75 ° C. ± 2 ° C. with stirring.

Preparation of aqueous phase Add first purified water and disodium EDTA to the main reactor. Heat to 75 ° C. ± 2 ° C. with stirring and homogenization.

Emulsion 9. When both phases reach 75 ° C. ± 2 ° C., pour the oil phase into the aqueous phase with vigorous stirring and homogenization. After 15 minutes of homogenization, check if the emulsion formed is uniform. Stir and homogenize for a longer time if necessary.
Cool to 10.37 ° C. ± 2 ° C.
11. Add premix D and stir until fully homogenized.
12 Add premix E and stir and homogenize well for at least 15 minutes.
13. Add Premix A with vigorous stirring.
14 Add Neolone PE® (phenoxyethanol (and) methylisothiazolinone), Premix B, Premix C, and Belides® (Bellis Perennis extract). Stir and homogenize until smooth.
15. Simuel NS® (hydroxyethyl acrylate (and) sodium acryloyldimethyltaurate copolymer (and) squalane (and) polysorbate 60) was added to the main reactor with vigorous homogenization and all material was in the tank. In some cases, agitation is incorporated. Stir and homogenize well for at least 15 minutes.
16. Add perfume FAV 22000® and homogenize.
17. Add premix F and stir and homogenize well for at least 15 minutes.
18. Samples are collected from the top and bottom and the pH is measured (range 5.0-6.5). The resulting change in pH between samples should not be any pH unit greater than 0.3, indicating homogeneity. If necessary, continue to stir until the aforementioned parameters are achieved.

Screening for volunteers Collective sampling:
Ten volunteers aged 18 to 60 were screened for study implementation. Participating subjects were given the first four letters of their names and the first letters of their last names, individual identification numbers (created by the electronic system) and protocol numbers.

2. Selection criteria Age level: 18 to 60 years old Phototype II and III according to Fitzpatrick classification
-Whole skin of the test site-Consent to visit the clinic on the date and time specified for evaluation according to the test method-Signature of informed consent form

3. Exclusion criteria • Pregnancy or breastfeeding • Use of anti-inflammatory or immunosuppressive agents • Personal history of atopy • Use of local or systemic photosensitization therapy • History of phototoxic or photoallergic reactions • Sensitization or irritation to local products・ History of light-induced lesions such as urticaria, lupus erythematosus, light-induced rash, herpes simplex ・ Presence of active inflammatory skin disease at the test site ・ Presence of neurological lesions at the test site ・ Active skin lesions・ History of sensitization or irritation to topical products ・ Frequent exposure to sun or tanning beds ・ Use of newly developed drugs within the last 6 months

Method 1. Operating procedure:
Following the initial procedure, the minimum amount of erythema required to induce pigmentation in each volunteer was determined as described below.

a. Calculation of minimum erythema amount To evaluate the minimum erythema amount (MED), a preliminary test was performed on each volunteer. Six exposures were applied to each volunteer's unprotected skin, and each exposure was 12% higher than the previous exposure in a geometric progression. The median dose has already been determined by Fizpatrick Phototype and is shown in Table 1 below.

  After irradiation, the volunteer was withdrawn and instructed to return after 24 hours. Exposure data was recorded for each volunteer.

b. Read After irradiation, each volunteer is released and instructed to return within 24 hours, so that each volunteer's exposure site is kept constant for each volunteer from a predetermined distance in a vertical position. Read by illumination. The MED then decided for each candidate.

  Individual minimum erythema dose (iMED) was defined as the minimum ultraviolet (UV) irradiation necessary to produce a clearly defined contoured erythema at the exposed site and was used as a reference during the testing phase.

  Therefore, sub-sites that do not show erythema are a necessary criterion for test evaluation. If this does not occur, a new application must be performed to determine iMED.

c. Induction of pigmentation After iMED determination, each test site located beside the back rib centerline between the back pelvis and shoulder ribs was marked with a marker on the lying volunteers. The three ranges designated for application of the product were defined, that is, site B, site E, and site F. Each site was 35 cm ² (07 × 05 cm). Irradiation equivalent to 1.5 times the minimum erythema amount already calculated for each volunteer was applied to each of the defined areas. This application was repeated twice, so that each site was irradiated three times in total.

d. Product Application After irradiation, the volunteers were withdrawn and instructed to return 72 hours later for photographic review and colorimetric evaluation. The subject was tested in triplicate for each of sites B, E, and F corresponding to three different irradiated regions to provide a total of three test sites and nine pointing regions per subject. After the evaluation, 2 mg of each test substance was applied to the irradiation region indicated by the test site of each subject once a day according to the following sequence.
Site B: Hydroquinone 2%
Site E: topical cosmetic composition of the present invention Site F: negative control: site where product is not applied

  In order to optimize product penetration and avoid product movement, hand contact or UV exposure, the product application site was shielded with filter paper and held with translucent adhesive tape. Volunteers returned to the clinic for application, reading and evaluation according to Table II below.

e. Colorimetric evaluation Colorimetric evaluation was performed using a color difference meter. All measurements were performed in triplicate and the L ^* a ^* b ^* parameter average for each volunteer was recorded. The L ^* parameter was separately statistically analyzed as its value decreased.

f. Statistics The parameter L ^* was compared to see if there were statistically significant differences between the treatment and control sites and between experimental time points. This comparison was performed by Student's t test on the paired data.

Results Treatment was assessed clinically and colorimetrically on the days of T7, T14 and T21. Site B containing a positive control (hydroquinone 2%) showed a colorimetric average for each experimental time as shown in FIG. FIG. 1 illustrates progressive whitening over time that became statistically significant after 21 days. Table III below shows the results of the L ^* comparative test between the T0 average of region 1 (site B) and other experimental times. Table IV shows raw data of individual results for each volunteer's region 1 (site B) by L ^* , a ^* and b ^* for each of T0, T07, T14 and T21.

FIG. 2 illustrates the results obtained at site E, i.e., the application position of the evaluated topical cosmetic composition of the present invention. FIG. 2 is a diagram illustrating progressive whitening over time that becomes statistically significant after 14 days. Table V below illustrates the results of a comparative test of L ^* between the T0 average of region 2 (site E) and other experimental times. Table VI shows raw data of individual results for each volunteer's region 2 (site E) by L ^* , a ^* and b ^* for each of T0, T07, T14 and T21.

FIG. 3 exemplifies progressive whitening (natural degradation of synthesized melanin) without any significant difference during the experimental time for control position site F, ie where nothing has been treated for irradiation. Yes. Table VII below shows the results of a comparative test of L ^* between the T0 mean of the control area (site F) and other experimental times. Table VIII shows the raw data of the individual results of each volunteer's control area (site F) by L ^* , a ^* and b ^* for each of T0, T07, T14 and T21.

  FIG. 4 illustrates a comparison between the mean of the colorimetric values in treatments 1 and 2 and the control during the evaluation time. Table IX illustrates that only the topical cosmetic compositions of the present invention show a statistical reduction in pigmentation compared to the temporary reduction in pigmentation observed in the control group.

Discussion In experimental models where there is UV-induced pigmentation (melanogenesis) but pre-existing pigmentary dysfunction, clinical pigmentation in the treatment area will gradually decrease over time. All sites including untreated controls were evaluated using a colorimeter and showed a significant reduction in pigmentation by T21.

  This experiment was therefore conducted to relatively evaluate that the treatment was the quickest and caused the most significant depigmentation. Since all treatments were applied to each volunteer at the same time, the variation in melanogenesis ability was considerably reduced. Thus, depigmentation would have occurred at the same rate in all of each volunteer's test sites.

  From this premise, the whitening effect was clinically observed over time for each site, which already considered visual evaluation and comparative analysis.

  To improve the accuracy of these observations and enable objective, consistent and reproducible evaluations, colorimeters can be used as an auxiliary instrument evaluation to detect differences that cannot be detected by the human eye did.

In a colorimeter, the L ^* parameter produced by the colorimetric measurement is an index directly related to skin lightness. The higher the value of L ^*, the brighter the evaluated area.

Since it deals with experimental melanogenesis, progression of depigmentation was predicted when treatment was assessed clinically and by a colorimeter. In control sites that were irradiated but not treated, hydroquinone showed a significant colorimetric improvement from T21 to L ^* , nonetheless, the whitening level was statistical when compared to hydroquinone T07 and T14. Scientifically low.

  Further examination of the data over time gave different results as follows. Hydroquinone: significantly improved from T21. The topical cosmetic composition of the present invention: significantly improved from T14, showing a statistically significantly higher whitening level when compared to the control. Thus, the topical cosmetic composition of the present invention provided a quicker and more significant whitening effect (higher whitening index) compared to hydroquinone.

  FIG. 5 shows a photograph of clinical data supporting the colorimetric results, where a greater average whitening effect was obtained in the position with the new formulation. Hydroquinone treatment and the new formulation were similar to the end of the study, but the new formulation is faster and provides a more marked whitening indication.

Example 2
The following examples illustrate the preparation of a cream according to the invention as described herein.

  The composition is prepared as in Example 1. More specifically, after Premix E is added to the emulsion, Neolone PE (phenoxyethanol and methylisothiazolinone) and cyclomethicone are added under high shear homogenization and mixed for about 15 minutes. A thickener containing xanthan gum is added to the oil phase.

Example 3
The following examples illustrate the preparation of a cream according to the invention as described herein.

  This composition was prepared as in Example 1.

Example 4
The following examples illustrate generally applyable methods for administering the compositions according to the invention described herein.

  The topical cosmetic composition is administered topically to the skin of the subject treated by conventional means. This is preferably done by use of a serum or cream gel formulation. Thus, the topical formulation can be applied to the desired skin surface area using, for example, a fingertip.

  For topical administration of the cosmetic composition, subjects should first be instructed to gently clean the affected area and tap to dry. The topical cosmetic composition may then be applied directly to the affected area, or dispensed into the palm or appropriate container and the substance removed therefrom and applied to the skin area to be manually treated.

Example 5
The subject has undesirable skin pigmentation. The topical cosmetic compositions described herein are administered topically to undesirable pigmented areas of the subject's skin. It is expected that undesired pigmented areas of the subject's skin will be whitened.

Example 6
The subject has vitiligo. The topical cosmetic compositions described herein are administered topically to the remaining areas of the subject's normal skin. It is expected that the remaining area of the subject's normal skin will be whitened to make the entire skin uniform.

Example 7
The subject has a stain due to age. The topical cosmetic compositions described herein are administered topically to the affected skin area of a subject. It is predicted that the spots due to age will be whitened.

  All publications cited herein are indicative of the level of skill of those skilled in the art to which the invention described herein pertains. All of these publications are incorporated herein by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.

  Thus, while the invention has been described, it will be apparent that it can be altered or varied in many ways. Such changes and modifications are not to be regarded as a departure from the spirit and scope of the invention, and all such changes and modifications are intended to be included within the scope of the following claims.

Claims (13)

Philanthus extract,
A topical cosmetic composition comprising Belis extract and licorice extract.   The topical cosmetic composition according to claim 1, wherein the phyllanthus extract comprises a philanthus embrica extract.   The topical cosmetic according to claim 2, wherein the extract of Philanthus embrica comprises a fruit extract of Philanthus embrica, the extract of beris perennis comprises a flower extract of belith perennis, and the licorice extract comprises a root extract of licorice. Composition.   Based on the total weight of the composition, the Philanthus Emblica extract is present in an amount of about 0.5 wt% to about 2 wt%, the Beris Perennis extract is present in an amount of about 1 wt% to about 20 wt%, and the licorice extract The topical cosmetic composition of claim 2, wherein the product is present in an amount of about 0.01 wt% to about 1 wt%.   The topical cosmetic composition of claim 2, further comprising at least one sunscreen.   The topical cosmetic composition of claim 5, wherein the at least one sunscreen is present in an amount of about 0.5 wt% to 30 wt%, based on the total weight of the topical cosmetic composition. At least one sunscreen
A first sunscreen selected from the group consisting of methylenebis-benzotriazolyltetramethylphenol, diethylaminohydroxybenzoylhexylbenzoate, coated zinc oxide and combinations thereof, and ethylhexyl methoxycinnamate, isoamyl methoxycinnamate, homo 6. A topical composition according to claim 5, comprising a second sunscreen selected from the group consisting of ethylhexyl salate salicylate, octocrylene, polysilicone-15, butylmethoxydibenzoylmethane, menthyl anthranilate, ethylhexyldimethyl PABA, and combinations thereof. Cosmetic composition.   8. The first sunscreen is present in an amount from about 1 wt% to 20 wt% and the second sunscreen is present in an amount from about 1 wt% to about 10 wt%, based on the total weight of the topical cosmetic composition. The topical cosmetic composition described.   The topical cosmetic composition of claim 7, wherein the first sunscreen is methylene bis-benzotriazolyl tetramethylphenol and the second sunscreen is ethylhexyl methoxycinnamate.   The topical cosmetic composition of claim 2, further comprising water and at least one cosmetically acceptable excipient.   The topical cosmetic composition of claim 10, wherein water is present in an amount of about 3 wt% to about 95 wt%, based on the total weight of the composition.   At least one cosmetically acceptable excipient is an antioxidant, chelating agent, pH adjuster, emollient, thickener, preservative, emulsifier, wetting agent, humectant, suspending agent, fluorescent The topical cosmetic composition of claim 10, comprising one or more components selected from the group consisting of whitening agents, stabilizers, penetration enhancers, fragrances, colorants and combinations thereof.   A method of whitening skin pigmentation in a subject comprising topically administering a therapeutically effective amount of the topical cosmetic composition of claim 1 to the skin of the subject in need thereof.

Images