cosmetic, non-therapeutic method to decrease dermatological signs of aging in human skin and skin ca

专利摘要:
METHODS FOR THE TREATMENT OF SKIN. These are methods of treating the skin with at least two alternating treatment modalities to improve health and/or reduce signs of aging. Some methods according to the present invention may comprise topically applying at least two separate compositions, in a sequential, rotational or alternating manner to overcome adaptation, tolerance or sensitization phenomena.
公开号:BR112017019054B1
申请号:R112017019054-0
申请日:2016-03-04
公开日:2021-05-11
发明作者:Uma Santhanam；Jolanta Idkowiak-Baldys；Daniel Thorn Leeson；Anthony David Gonzalez；Pradeep H. Yadav；Olga Maria Martinez-Avila；Lauren POLICELLI；Glen Thomas Anderson；Russell J. Wyborski；Simon Dutton；Jeanine SCHOEN；Dana VON BARGEN
申请人:Avon Products, Inc；
IPC主号:

专利说明:

CROSS REFERENCE TO RELATED ORDERS
[001] This application claims priority under Title 35 of USC § 119(e) of provisional patent application serial number US 62/128647, filed March 5, 2015, the contents of which are incorporated herein by way of reference in its entirety. FIELD OF THE INVENTION
[002] The invention relates generally to methods for reducing signs of aging and/or improving the health of human skin. More particularly, the invention relates to the rotational, serial or alternating use of two or more different treatments to improve the appearance of the skin, including remediating the signs of aging. The two or more different treatment modalities may comprise, without limitation, the topical application of compositions containing active principles for skin care, use of devices, for example, to impart electromagnetic or mechanical energy to the skin, application of masks (which can be eluted with active ingredient), subcutaneous injection, oral administration of active ingredients and chemical peels (scaling). Treatment modalities can be performed at least once a day for a treatment period that can range from 1 to 31 days, and then treatment modalities are alternated or rotated in series. BACKGROUND
[003] Numerous skin care products have been developed to improve the appearance of human skin. Many of the most effective methods employ topically applied compositions that contain one or more active ingredients known to beneficially affect the skin. For example, compositions that contain retinoids, particularly retinol, have been shown to be effective in combating fine lines, wrinkles and other indications of skin aging, such as sagging. Topically applied retinoids promote the formation of collagen and elastin in the skin. Compositions containing retinoids can be used to treat a multitude of unwanted skin conditions such as acne and wrinkles. However, the benefits of retinol therapy are known to stagnate with prolonged use in some individuals.
[004] Phytol is another active agent that is known to promote skin health and remedy or lessen signs of skin aging. A composition for optimizing skin appearance comprising both phytol and retinol is described in U.S. publication number 2003/0198657 to Menon, the description of which is incorporated herein by reference.
[005] It has been recognized that the skin may become accustomed to cosmetic products, and the observable skin benefits may begin to decline after an initial treatment period. It has also been observed by dermatologists in clinical trials that the skin may develop tolerance to retinoids, and the use of higher concentrations of retinoid-containing compositions over time might be necessary to maintain the desired efficacy in some individuals. This phenomenon is analogous to adaptation, which is well described in biological systems. For example, at a cellular level, stimulation of receptors leads to desensitization and a diminished response. A period of resensitization or "rest" is required before the same level of response can be seen again.
[006] Therefore, it is an object of the present invention to provide skin treatment methods that overcome the problem of tolerance and/or provide optimized efficacy and/or improve the health and/or appearance of human skin. It is another object of the present invention to provide treatments for human skin that involve the rotational, serial and/or alternate use of at least two distinct treatment modalities. It is another object of the present invention to provide methods for improving the health and/or appearance of human skin which involve the rotational, serial and/or alternating topical application of at least two skin care compositions.
[007] The foregoing discussion is presented only to provide a better understanding of the nature of the problems confronting the technique and should in no way be construed as an admission with regard to the prior art or citation of any reference in the this document is to be construed as an admission that such reference constitutes the "prior art" to the present application. SUMMARY OF THE INVENTION
[008] In accordance with the aforementioned and other objectives, the present invention provides methods for the improvement of one or more signs of dermatological aging of human skin and/or improvement of human skin health, the methods comprising alternating /take turns between a plurality of (eg two, three, four, five, six, seven or more) different treatment modalities. Each treatment modality is administered over a period of time (eg, at least once a day for 1 to 31 days), which may be the same or different from the treatment time period for each of the other treatment modalities. Treatment modalities may include application of topical compositions to the skin, application of electromagnetic or mechanical energy (eg, ultrasound, vibration, light (visible, infrared, etc.)) to the skin, mechanical or chemical peeling (eg, microdermabrasion , chemical peeling, etc.), application of skin masks (which may optionally elute skin care active principles on the skin), oral administration of active principles, etc. The treatment modality may include allowing the skin to "rest" by not treating it in any particular way other than routine hydration and/or washing. In some implantations, at least one of the plurality of treatment modalities entails the topical application of an active skin care ingredient to an area of the skin (eg, the face) at least once a day for a period of 1 to 31 days. In some implantations, at least two of the plurality of treatment modalities entail the topical application of an active skin care ingredient to an area of the skin (eg, the face) at least once a day for a period of 1 to 31 days, in which the active skin care principles and treatment periods may differ from one another. In some implantations, at least one of the plurality of treatment modalities entails the application of mechanical or electromagnetic energy to an area of the skin (eg, the face) at least once a day for a period of 1 to 31 days . In some implantations, at least one of the plurality of treatment modalities entails exfoliation (eg, chemical or mechanical) of an area of skin (eg, the face) at least once a day for a period of 1 to 31 days , for example, with the use of a chemical peel (e.g., phenol), microdermabrasion, or with a topical composition comprising an effective amount of a peeling agent. In some implantations, the method comprises the use of at least two treatment modalities, in which a first composition is applied topically to an area of the skin (eg, the face) one or more times a day for a first period of time ( for example, 1 to 31 days), followed by topical application to the same area of skin of a second composition one or more times a day for a second period of time (for example, 1 to 31 days).
[009] Without wishing to be bound by any particular theory, it is believed that the rotational treatment regimen overcomes, at least in part, the adaptation and/or tolerance phenomena through which the effect of certain active principles or treatments diminishes or stagnates over time. It is also theorized that rotational treatments can act in a cooperative and/or synergistic way, whereby one treatment modality optimizes the effectiveness of the other. For example, a desquamation treatment is contemplated to improve the penetration of a subsequently applied active ingredient, or an anti-inflammatory treatment is contemplated to reduce erythema associated with retinol use and hence allow for higher levels or later application of retinoids .
[010] In one aspect of the invention, methods are provided for treating the skin to improve the health and/or appearance thereof which comprise administering a first treatment modality (e.g., topically applying a first composition comprising an active agent ) to an area of skin that requires such treatment at least once a day for a first period of time (for example, a predetermined period of time), typically from 1 to 31 days, from 2 to 31 days, from 3 to 31 days, from 4 to 31 days, from 5 to 31 days, from 6 to 31 days, from 7 to 31 days, from 1 to 7 days, from from 2 to 7 days, from 3 to 7 days, from 4 to 7 days, from 5 to 7 days or 7 days, etc. The period of time can be "predetermined", which means that, before starting the regimen, the user determines or is instructed (for example, by written instruction that accompanies the product or obtained electronically from a computer) to use the mode of treatment (for example, topically applying a skin care composition) daily for a fixed number of consecutive days. Alternatively, the time period can be determined by the user's reaction and/or response to daily use of the first treatment modality (eg, topical application of the first composition). For example, the first time period may start on the first day of administration/application and end upon the appearance of irritation and/or redness, or may end when there are observable improvements and/or reductions in a sign of skin aging, or it can end at the beginning of a stagnation of effectiveness, etc. In some implantations, the first treatment modality (eg, topical application of a skin care composition) is used on the same area of skin for at least two, three, four, five, six, seven or more days I achieved you. In other implantations, the first treatment modality (eg, topical application of a skin care composition) is used for only one day. In other implantations, the first treatment modality (eg, topical application of a skin care composition) is used daily for seven days.
[011] The first time period may be followed by a second time period in which the first treatment modality is discontinued and/or the use of a second treatment modality is initiated. For example, the first mode of treatment may comprise topically applying a first composition (which comprises a first active agent) for a first period of time, and thereafter: (i) the first composition is not topically applied to the same area of skin daily for a second period of time, (ii) the first composition continues to be applied to the same area of skin daily, but in changed amounts (eg dose (mg/cm2) is increased or decreased with respect to the first time period) or changed frequency (e.g., applied more or less times per day with respect to the first time period) during a second time period and/or (iii) a second composition is applied -daily (eg at least once a day) to the same area of skin for a second period of time. In one modality, the first treatment modality is discontinued during the second time period.
[012] The second time period is typically from 1 to 31 days, from 2 to 31 days, from 3 to 31 days, from 4 to 31 days, from 5 to 31 days, from 6 to 31 days, from 7 to 31 days, from 10 to 31 days, from 14 to 31 days, from 5 to 31 days, from 6 to 31 days, from from 7 to 31 days, from 1 to 7 days, from 2 to 7 days, from 3 to 7 days, from 4 to 7 days, from 5 to 7 days or from 7 days days, etc. In some implantations, a second treatment modality (eg, topical application of a skin care composition) is administered to the same area of skin for at least one, two, three, four, five, six, seven or more consecutive days. In some modalities, the second time period is shorter, equal to or longer than the first time period. In some modalities, the second time period is one day. In some arrangements, the second time period is seven days. The second period of time can be predetermined (eg according to written instructions) or can be determined by the user's reaction and/or response to the daily use/application of the second treatment modality. The second time period typically starts on the day after the last day of the first time period, although it is contemplated that the end of the first time period and the beginning of the second time period may be separated by one, two, three, four, five, six or seven days or more, which may be a predetermined period of time, for the skin to "rest" without treatment with the first or second treatment modality. This could entail treating the skin only with a composition that has no active skin ingredients (for example, with just a moisturizer treatment) or applying absolutely nothing during this time. It is also contemplated that the second time period may partially (but not completely) overlap the first time period, so that the first and second modalities are administered to the same area of skin daily during a nude. mere days (eg one day, two days, three days, etc.). The second time period may therefore overlap, be integrated by or consecutive to the first time period, or it may follow the first time period after an interval of one day or more. The second treatment modality may comprise the topical application of a second skin care composition that is different from the first skin care composition. For example, if the first skin care composition comprises an effective amount of a retinoid (eg, retinol), then the second skin care composition may, in some embodiments, comprise a different retinoid, a different amount of the same retinoid or may be free of retinoids (eg, retinol). In some implants, the second treatment regimen may lead to no treatment, which means that no composition is applied topically to the skin. To illustrate, a treatment regimen in accordance with the invention may comprise alternating between a first modality which comprises topically applying a retinol formulation, followed by a second modality comprising topically applying a second formulation which does not comprise retinol (or any retinoid) and subsequently repeat those steps one or more additional times.
[013] Upon completion of the second treatment modality, the regimen may continue with re-administration of the first treatment modality to the same area of skin during said first time period. The first time period can start on the day after the last day of the second time period. Alternatively, the second time period may be followed by a "rest" period (as described above) before starting the first treatment modality. In another embodiment, the second treatment modality may be followed (on the following day or after any "rest" period) by a third treatment modality for a third period of time.
[014] The regimen can continue in this way with the use of any number of treatment modalities. For example, in one embodiment of the invention, seven different treatment modalities are administered to the subject for seven time periods in sequence. Time periods under this mode can be in the range from 1 to 31 days, more typically from 1 to 7 days or from 1 to 3 days, or 1 day. In one modality, the treatment regimen comprises seven different treatment modalities, each of which is administered for at least one day (or for just one day) over a period of seven consecutive days, provided that any two days do not have the identical treatment regimen.
[015] In several modalities, in which two treatment modalities are employed, the modalities can be indicated as "A" and "B", respectively, where "A", "B" can each represent a topical composition , identify a treatment and/or administration material or materials, duration, intensity of treatment modality, etc., repeated at different intervals (per application; per day; per week; etc.). In some modalities, the treatment regimen can be represented as (AB)n, where modalities A and B are employed sequentially and then the process is repeated n-1 times (where n is typically greater than 2, greater than 3, greater than 4, greater than 8 or greater than 12, etc.). For example, in the case where n=4, this can be represented as ABABABAB. Additional treatment modalities may also be included. For example, in the case where a third treatment modality "C" is included, the regimen can be represented as (ABC)n, where modalities A, B and C are employed sequentially and then the process is repeated n-1 times. For example, in the case where n=4, this can be represented as ABCABCABCABC. Additional treatment modalities can also be included. In another embodiment, treatment modalities may be interspersed with rest periods in which no active ingredients or non-active skin care formulations are used.
[016] In some embodiments, at least one of the plurality of treatment modalities comprises the topical application of a composition comprising an effective amount of at least one active skin care ingredient. The active ingredient is normally dissolved or dispersed in a physiologically compatible carrier (eg an emulsion, oil, gel, serum, etc.). The effective amount of active ingredient can comprise, for example, from about 0.0001% to about 25% (by weight) based on the weight of the entire composition, more typically from about 0.001% to about 5% by weight (from about 0.01 to 1% or 0.1 to 0.5% by weight). The composition can include additional adjuvants and excipients such as film formers, oils, resins, elastomers, waxes, thickeners and rheology modifiers, gelling agents, stabilizers, emollients, conditioning agents, humectants, chelating agents, pH adjusters, preservatives, fragrances, fillers and powders, colorants and optical modifiers, sunscreens, etc. The vehicle can comprise water or can be anhydrous or substantially anhydrous. The vehicle can comprise one or more oils, including ester oils, vegetable oils, fatty alcohols, hydrocarbon oils, mineral oils, polyolefin oils, silicone oils and the like.
[017] In one embodiment, at least one of the plurality of treatment modalities comprises the topical application of a composition comprising an effective amount (e.g., from about 0.05% to about 5% ( by weight)) of retinoid (e.g., retinol, retinaldehyde, retinyl palmitate, etc.) at least once a day (or once a day, etc.) for a first period of time from 1 day to 31 days, more typically from 2 to 31 days, from 3 to 14 days, from 5 to 10 days, or for 7 days. In an implant, the first composition comprises an effective amount of a retinoid (eg, retinol). In another implantation, the second composition comprises an effective amount of a retinoid (eg, retinol). In an implant, the first composition comprises an effective amount of a retinoid (for example, retinol) and the second composition does not comprise an effective amount (for example, from about 0.05% to about 5% (by weight) )) of retinoid (eg, retinol). In another implantation, the second composition comprises an effective amount of a retinoid (for example, retinol) and the first composition does not comprise an effective amount (for example, from about 0.05% to about 5% (by weight) ) of retinoid (eg, retinol).
[018] In some implantations, at least one of the plurality of treatment modalities entails the topical application of an effective amount of a retinoid (eg, retinol) at least once a day (or once a day) for a first time period from 1 day to 31 days, from 2 to 31 days, from 3 to 14 days, from 5 to 10 days, from 1 to 7 days, from 1 to 5 days, from 1 to 3 days or for one day. In an implantation, at least one of the plurality of treatment modalities entails the topical application of an effective amount of a retinoid (eg, retinol) at least once a day (or once a day, for example, in the evening ) for seven consecutive days.
[019] In an implantation, the first treatment modality (for example, the topical application of a first composition comprising a skin care active ingredient) is administered daily for five consecutive days (eg, second Friday) and the second treatment modality (for example, the topical application of a second composition comprising a different skin care active ingredient), which is different from the first treatment modality, is administered daily during the next two days (eg Saturday to Sunday). In another implantation, the first treatment modality (for example, the topical application of a first composition comprising a skin care active ingredient) is administered daily for seven consecutive days (for example, Monday to Sunday ) and the second treatment modality (for example, the topical application of a second composition comprising a different skin care active ingredient), which is different from the first treatment modality, is administered daily during the sessions. te following days (eg Monday to Sunday). The regimen may be repeated a plurality of times, including at least one, two, three, four or more additional times, and typically until an improvement in skin health and/or appearance is noted. The first treatment modality may involve the topical application of a composition which comprises an effective amount (for example 0.05% to 5% by weight) of a retinoid such as retinol or retinyl palmitate. The second modality of treatment may involve the topical application of a second composition which comprises, for example, an effective amount of a skin care active in addition to a retinoid. In an implant, the second composition comprises an effective amount of alpha-hydroxy acid. In an implant, the second composition comprises an effective amount of an antioxidant. In an implant, the second composition comprises an effective amount of a botanical extract (eg Tiliacora triandra extract, including hydroponically developed variants). In another embodiment, the second composition comprises moisturizers, emollients and/or humectants and can comprise additional active ingredients or can be free of additional active ingredients (for example, phytol, glycolic acid and/or niacinamide). In another embodiment, the second composition does not comprise an effective amount of retinoids (eg, retinol) or is free of retinoids (eg, retinol).
[020] In some modalities, the first topical cosmetic composition may comprise at least one active skin principle that has the effect of improving the appearance and/or health of the skin, including, without limitation, decreasing the appearance of signs of aging (eg, chronological, hormonal, environmental and/or photo-aging). In some embodiments, the first active agent can be a substance (eg, small molecule, amino acid, protein, peptide, nucleic acid, extract, etc.) that increases the production of collagen, procollagen, elastin, glycosamino glycan (GAG) and/or hyaluronic acid in the skin and/or reduces pigmentation in the skin and/or modulates (increases or decreases) lipolysis or lipogenesis in adipocytes. The active agent may be, without limitation, an agent that improves skin tightness (eg, reduces sagging), decreases the appearance of wrinkles and/or expression lines (eg, crow's feet, wrinkles, etc.), thickens the skin thinning, improves (eg evens out) skin tone, reduces the appearance of localized areas of pigmentation (eg sun spots, freckles, dark brown spots, age spots, etc.) , reduces the appearance of dark circles under the eyes and/or reduces the appearance of cellulite, etc. In some embodiments, the first composition may comprise one or more of the following: collagenase inhibitors, elastase inhibitors, upregulators/collagen stimulators, upregulators/procollagen stimulators, upregulators/elastase stimulators, regulators hyaluronic acid ascendants/stimulators, tyrosinase inhibitors, melanosome transferase inhibitors, melanogenesis inhibitors.
[021] In some embodiments, active agents may comprise one or more of the following: retinoids (eg, retinol and C2-20 esters thereof, such as retinol palmitate, retinol acetate and retinol propionate, retinal-aldehyde, acid 9-cis retinoic acid, 13-cis retinoic acid, all trans retinoic acid, phytanic acid, Vitamin A, and esters and salts of any thereof, etc.), a-hydroxy acids (eg, glycolic acid, lactic acid, citric acid, etc.), β-hydroxy acids (eg salicylic acid), salicylates, 5-α-reductase inhibitors (linolenic acid, linoleic acid, finasteride, etc.), vitamins (eg vitamins A, B , C, E, etc., and C2-20 esters thereof), PPAR-Y inhibitors, anti-inflammatories (eg TNF-α inhibitors), antioxidants (eg ascorbic acid, astaxanthin, beta -carotene, catechins, curcumin, ellagic acid and gallic acid derivatives (eg propyl gallate), ferulic acid derivatives (by and example, ethyl ferulate, sodium ferulate), glutathione (GSH), green tea extract, hexylresorcinol, idebenone, α-lipoic acid, lycopene, phytol, phytanic acid, TDPA and esters (eg, dilauryl) thereof , thioglycolic acid, reductic acid; rosmarinic acid; tannic acid; tetrahydrocurcumin; tocopherol and its derivatives, ubiquinone, uric acid and C2-20 esters of any thereof), phytochemicals (eg flavonoids and carotenoids), phytoalexins, stilbenoids (eg resveratrol), botanicals, product inhibitors/inverters Advanced Glycation End Product (AGE) (eg TDPA), purines; estrogen synthetase stimulating compounds (eg xanthine and caffeine and derivatives), amino acids (eg L-arginine, L-aspartic acid, L-glutamine, L-glycine, L-lysine, L-histidine, L-alanine , L-threonine, L-glutamic acid, L-taurine, L-proline, L-serine, etc., or C2-20 amides or esters and derivatives thereof, including enantiomers) and derivatives thereof (for example, carnitine, N-Acetyl Tyrosinamide, etc.), dipeptides (eg carnosine) and oligopeptides and C2-20 esters (eg palmitoyl) or amides thereof (eg palmitoyl oligopeptides), peeling agents ( for example, glycolic acid, salicylic acid, imidopercarboxylic acids, jasmonic acid, gentisic acid, 3,6,9-trioxaundecanedioic acid, etc., and derivatives of any of these), keratolytics (eg, allantoin, lactic acid, urea, etc.), astringents (eg witch hazel), antipruritic agents (eg camphor, menthol, etc.), anti-acne agents ( eg salicylic acid, sulfur, benzoyl peroxide, triclosan, etc.), steroids including corticosteroids (eg hydrocortisone) and sterols (eg β-sitosterols, phytosterols such as soy glycine sterols, pomegranate sterols , Brassica campestris sterols, canola sterols, etc.), soy isoflavone glycosides (eg genistin, daidzin and glycitin) and aglycones (eg genistein, daidzein and glycitein), depigmenting agents (eg hydroquinone , liquorice extract, kojic acid, niacinamide, etc.), pigmenting agents (eg, dihydroxyacetone), barrier function enhancing agents (eg, ceramides, such as ceramide-2, glycerides, cholesterol and their esters, alpha and omega-hydroxy fatty acids and esters thereof, etc.), serine protease inhibitors (eg soy proteins), and combinations thereof.
[022] In various non-limiting modalities, the active agent can be a substance that modulates (eg, up-regulates, down-regulates, stimulates, inhibits, etc.) the expression or activity of one or more of the following : retinoic acid receptor (RAR), retinoid X receptor (RXR), Carnitine palmitoyl transferase I (CPT-1), PLOD-2, Thymosin-β4, tenascin-X, WIPI-1, Nesprin-2, MAGP-1, tyrosinase, desmogleins 1 and 3, fibroblast growth factors (FGFs), paxillin, collagen 1, C-reactive protein (CRP), calcitonin gene-related peptide (CGRP), sirtuins (SIRT1 protein ), fibrillin-1, PPAR (eg a, Y, etc.) receptors, stearoyl CoA desaturase (SCD1), adiponectin, enzyme cyclooxygenase-2 (COX-2), metallothioneins, Lysyl oxidase similar to 1 (LOXL1 ), β-1-integrin, cytokines (eg I-CAM, IFN--, IL1-β, IL12, IL6, IL8, IL2, IP10, TNF-α, TNFr2, etc.) histamine (eg H1 , H2, etc.), adipose septa (eg re asporin, biglycan, decorin, dermatopontin, fibromodulin, fibronectin, galectin-1, laminin beta 2, lumican, MAGP-4, mimecan (osteoglycin), nidogen-1, nidogen-2 or prolargine, DICKKOPF-1, paxillin receptor , fibroblast growth factor receptor 1 (FGFR1), alpha-2-adrenergic receptor, beta-adrenergic receptor, phosphodiesterase, adenylate cyclase activator, serine proteinase (eg, trypsin inhibitor, neutrophil elastase, etc.) , matrix metalloproteinase (eg gelatinase B), fructosamine-3-kinase (FN3K or FN3K RP), matriptase MT/SP1, Monoamine Oxidase B (MAOB), growth factors (eg bFGF, PDGF, VEGF, etc. .), human tissue kallikreins (KLKs, e.g. KLK-5), calcineurin, etc.
[023] In some embodiments, the first or second composition comprises a C20-C25 terpene alcohol (eg, phytol) or a metabolite thereof (eg, phytanic acid). In some embodiments, the first or second composition comprises a retinoid (for example, retinol or retinol palmitate). In some embodiments, the first or second composition comprises a C20-C25 terpene alcohol (e.g., phytol) or a metabolite thereof (e.g., phytanic acid) and the other composition comprises a retinoid (e.g., retinol ).
[024] In some implantations, the first or second composition comprises a C20-C25 terpene alcohol (eg phytol) or a metabolite thereof (eg phytanic acid) and the other composition comprises a retinoid (eg retinol). The first and second compositions are applied in a series, sequential, rotary and/or staggered mode. Typically, alternate treatments are performed without a break in between, so that one starts the day after the other. Typically, the first time period will be from about a day to about a month (or from 3 to 20 days or from 5 to 10 days) and the second time period will be from about a day to about of a month (or from 3 to 20 days or from 5 to 10 days). The compositions can be applied in any order (for example, phytol treatment period followed by retinol treatment period or retinol treatment period followed by phytol treatment period), and the method may be repeated any number of times (eg once, twice, three times, etc.), to obtain any number of alternate treatments with said first and second compositions, and ideally for sufficient time to obtain a visible improvement in health and /or skin appearance (eg a reduction in the number and/or depth of wrinkles or fine lines). In some implantations, treatment is continued for at least 4 weeks, at least 8 weeks, at least 12 weeks or longer.
[025] In one aspect, a method is provided for decreasing the appearance of dermatological signs of aging (for example, fine lines and/or wrinkles and/or thinning of the skin and/or reduction of unwanted pigmentation and hyperpigmentation and /or sagging skin, etc.) and/or improved human skin health (eg improved barrier function, etc.), the method comprising the steps of: (1) applying topically to an area of the skin in need of such treatment, an effective amount (for example, from about 0.001 to 5% by weight) of a composition containing C20-C25 terpene alcohol (for example, phytol) or metabolite thereof (for example, phytanic acid) for a first period of time (eg 1 to 31 days, 3 to 20 days, 5 to 10 days or 7 days, etc.); and thereafter (2) topically applying, to the same area of skin, an effective amount (for example, from about 0.001 to 5% by weight) of a composition containing retinoide (for example, retinol) for one second time period (eg 1 to 31 days, 3 to 20 days, 5 to 10 days or 7 days, etc.). Steps can be performed in any order. Typically, the two time periods end and begin on consecutive days, so there is no intervening day without treatment. In some deployments, however, there may be a predetermined number of intervening days (eg, one, two, three, etc.) between the two treatment periods. The method may further comprise steps (1) and (2) by one, two, three, four or more additional times, ideally until an improvement in skin health and/or a reduction in dermatological signs of aging is noted. The method can be performed chronically or indefinitely for continuous treatment and/or prophylaxis. In some implantations, the method is for reducing the appearance of wrinkles and/or fine lines, including reducing the number of such wrinkles and/or fine lines, reducing the depth of such wrinkles and/or fine lines or prevent the development or progression of such wrinkles and expression lines. In some implants, the method is for reducing unwanted pigmentation in the skin, including, without limitation, reducing age spots, freckles, sun spots and the like, or for reducing the mottled appearance of the skin and/or smoothing the tone of the skin. skin.
[026] In another aspect, a method is provided to decrease the appearance of dermatological signs of aging (for example, treatment of wrinkles and/or expression lines and/or treatment of sagging skin/elastic improvement - city and/or uniformity of skin tone and/or reduction of unwanted pigmentation), which comprises the steps of: (1) topically applying, to an area of skin in need thereof, an effective amount (for example, from about 0.001 to 5% by weight) of a phytol-containing composition for a first period of time (e.g., 1 to 31 days, 3 to 20 days, 5 to 10 days or 7 days, etc.); and topically applying, to the same area of skin, an effective amount (for example, from about 0.001 to 5% by weight) of a composition containing retinol for a second period of time (for example, 1 to 31 days, 3 to 20 days, 5 to 10 days or 7 days, etc.), and (3) repeat steps (1) and (2) for at least one (eg two, three, four or more) additional time ( or repeat until improvement is noted). Steps (1) and (2) can be performed initially in any order and repeated in that order in step (3). The two time periods may end and begin on consecutive days so that there is no intervening day without treatment, or there may be a predetermined number of intervening days (eg, one, two, three, etc.) between the two treatment periods. The method can be performed for at least one, two, four, eight or twelve weeks or more, until a benefit is observed, including chronic or indefinite treatment for maintenance and/or prophylaxis.
[027] In one aspect of the invention, a method for decreasing dermatological signs of aging is provided which comprises, in any order, the steps of (1) applying topically to an area of skin in need thereof (e.g., skin of the face, neck, chest, hands, etc.), at least once a day (eg once a day in the evening or in the morning), a first skin treatment composition comprising, in a vehicle physiologically compatible (e.g., an oil-in-water emulsion comprising from 0.01 to 10% by weight of an emulsifier), an effective amount (e.g., 0.01% to about 1% by weight) of a retinoid (eg, retinol) for a first period of time ranging from 1 to 31 days (eg, 2 to 15 days, or for seven days); (2) implement a second treatment modality for a second period of time ranging from 1 to 31 days (eg, 2 to 15 days or for seven days); and (3) repeat steps (1) and (2) for a number of times (eg, four or more) sufficient to decrease said dermatological signs of skin aging (eg, treat wrinkles and/or lines expression and/or decrease the appearance of unwanted pigmentation). In an implantation, the second treatment modality comprises topically applying to said same area of skin at least once a day (e.g., once a day in the evening or in the morning) a second skin treatment composition. which is different from said first skin treatment composition (e.g., does not comprise an effective amount of a retinoid, such as retinol), and which may comprise, in a physiologically compatible vehicle (e.g., an emulsion of oil in water comprising from 0.01 to 10% by weight of an emulsifier), one or more skin active agents, including, without limitation, α-hydroxy acids (e.g. glycolic acid, lactic acid, citric acid , etc.) and/or antioxidants (eg ascorbic acid, beta-carotene, hexylresorcinol, tocopherol and their derivatives, including acetate, phytol, phthalic acid and thiodipropionic acid esters and their di-alkyl esters, including di-lauryl esters ), such as from about 0.01% to about 10% by weight of phytol, from about 0.01% to about 10% by weight of glycolic acid and/or from about 0.01% to about 10% by weight of acid thiodipropionic or esters (eg, di-lauryl esters) thereof. Typically, in the practice of the method according to this modality, the first and second time periods are consecutive so that one starts on the day after the last day of the other, and in a particular implantation, both the first and the second time period is seven days.
[028] Typically, the method is repeated for a period of time sufficient to improve skin health and/or obtain a desired benefit of decreasing signs of aging in the skin (eg, reduction in number or severity of wrinkles and /or expression lines, reduced sagging/improved elasticity, thinned skin thickening and/or more even skin tone and/or reduction of unwanted pigmentation, etc.). This can entail topical application at least once a day for at least a week, at least two weeks, at least four weeks, or at least eight weeks or more. In some embodiments, the compositions are applied directly to a specific location on the skin (ie, directly over a wrinkle, aimed at a hyperpigmented spot, under the eyes, etc.). In some embodiments, the first and/or second compositions will be applied to the skin in an amount from about 0.001 to about 100 mg/cm2, more typically from about 0.01 to about 20 mg/ cm2 or from about 0.1 to about 10 mg/cm2.
[029] In yet another aspect of the invention, a kit is provided which comprises: (i) a first composition comprising a topically acceptable vehicle (e.g., emulsion, gel or serum) and an effective amount (e.g. , from about 0.001 to 5% by weight) of a retinoid (for example, retinol or its esters, such as acetate, propionate, palmitate, etc., retinaldehyde, retinoic acid, etc.); and (ii) a second composition comprising a topically acceptable vehicle (e.g., emulsion, gel or serum) and an effective amount (e.g., from about 0.001 to 5% by weight) of a skin active ingredient, as an antioxidant, alpha-hydroxy acid, botanical product, etc., including, for example, phytol and/or TDPA (or their di-alkyl esters) and/or glycolic acid and (iii) written instructions for topically applying said first and second compositions, in any order, in alternating mode, so that the first composition is applied at least once a day for a first time period and said second composition is applied at least once a day for a second time period . Instructions may also indicate that alternate treatments are performed without an interval between them, so that one starts the day after the other, or they may provide a predetermined interval (for example, one day, one week, etc. .), between the end of one treatment period and the beginning of the next. Instructions may indicate that the first time period will be from about a day to about a month (or from 3 to 20 days, from 5 to 10 days or 7 days) and the second time period will be from about a day to about a month (or from 3 to 20 days, from 5 to 10 days or 7 days). Instructions may also indicate that the compositions may be applied in any order (for example, first treatment period followed by second treatment period or, alternatively, second treatment period followed by first treatment period). Instructions may indicate that treatments can be repeated. Instructions can specify any number of alternating treatments (for example, one, two, three, four or more) with said first and second compositions. Instructions may indicate that treatment should be carried out long enough to achieve a visible improvement in the health and/or appearance of the skin (eg, a reduction in the number and/or depth of wrinkles or fine lines, reduction in unwanted pigmentation, etc.). In some implantations, instructions indicate that treatment is continued for at least 4 weeks, at least 8 weeks, at least 12 weeks or longer. Written instructions may be included on the container, associated packaging, or on a website. In the case where the instructions stay on a website, the container or package will comprise written instructions for accessing the website (including, for example, a QR code, etc.). The first and second compositions may be physically separated from each other, for example, in separate containers, or within separate reservoirs within the same container. The first and second compositions can each be supplied in amounts corresponding to the same predetermined number of treatments (eg, equivalent number of doses). The first and second compositions can each be contained in a plurality of containers that correspond to an individual dose. The first and second compositions may each be contained in containers that contain written instructions for the period of use of each composition. The first and/or second compositions can also include a sunscreen.
[030] In yet another aspect of the invention, there is provided a skin care product comprising a container comprising a first reservoir containing a first skin treatment composition and a second reservoir containing a second skin treatment composition, different from said first skin treatment composition, a first pump in fluid communication with the first reservoir for dispensing said first skin treatment composition, and a second pump in fluid communication with the second reservoir for dispensing said second skin treatment composition, wherein each pump is optionally covered with a removable cap. The container may be in the form of an elongated cylinder having the first pump and the second pump disposed on opposite ends thereof. The first and second reservoirs may or may not be separable from each other. The container may comprise (for example, on a visible surface thereof or on a label affixed thereto) visible identifiers to distinguish the first and second reservoirs. In one embodiment, the identifiers may comprise alphanumeric symbols (e.g., a number or letter identifying one reservoir/composition and a different number or letter identifying the other reservoir/composition). In another embodiment, the identifiers may comprise a visual identifier, such as colors, patterns, illustrations, different images, etc. (for example, a color that identifies a reservoir/composition and a different color that identifies the other reservoir/composition). Alphanumeric combinations or identifiers and other visual identifiers can also be used. In another embodiment, identifiers comprise a symbol in addition to an alphanumeric symbol. The product will typically include, on the label, packaging, associated website, etc., written instructions for topically applying, to an area of the skin in need of such treatment, an amount of said first skin treatment composition (e.g. , at least once a day) during a first period of time comprising from 1 to 31 days, from 2 to 15 days or 7 days, followed by topically applying, to said area of skin, said second composition of skin treatment (for example, at least once a day) for a second period of time comprising from 1 to 31 days, from 2 to 15 days or 7 days. In some implantations, the first composition may comprise a topically acceptable vehicle (for example, an oil-in-water emulsion with 0.01 to 10% by weight of an emulsifier) and an effective amount (for example, from about 0.001 5% or 0.05 to 1% by weight) of a retinoid (for example, retinol or its esters such as acetate, propionate, palmitate, etc., retinaldehyde, retinoic acid, etc.), typically retinol; and (ii) a second composition comprising a topically acceptable vehicle (for example, an oil-in-water emulsion with 0.01 to 10% by weight of an emulsifier) and an effective amount (for example, from about 0.001 5% or 0.05 to 1% by weight) of an active ingredient for skin, such as an antioxidant, alpha-hydroxy acid, botanical product, etc., including, for example, phytol and/or TDPA (or its di-alkyl esters) and/or glycolic acid. The first and second skin care compositions may, for example, each have a viscosity between about 10,000 cps and 250,000 cps (for example, between 25,000 cps and 150,000 cps, or between 50,000 and 100,000 cps, when measured at a shear rate of 10 s-1 at 25 °C, and may have a similar or distinct attribute selected from tactile sensation, aroma, color or other visual attribute and/or the perception of cooling or heating. implantations, the viscosity of said second composition is within ±50%, ±40%, ±30%, ±20%, ±10% or ±5% of the viscosity of said first composition. In some embodiments, the product will include identifiers visible that indicate each day of the week, for example, printed on a label affixed to the container. For example, the product may have a label adhered to the container and the label may have the letters, such as "STQQSSD (MTW TH F SA SU, in English)", printed on it to identify each day of the week. A sticker for the user to place over the appropriate day of the week on the label on which the treatment regimen began, to serve as a reminder to alternate between the first and second treatment compositions each week on that particular day. In a related aspect, a system is provided comprising: the packaged skin care product and a server for sending notifications, over a network (for example, a cell phone, wireless, cable, internet, satellite, etc.). ), which instructs a user of the packaged product as to which of said first and second skin care compositions to apply topically to said skin. Notifications can be sent daily or can be sent at least one day during said first time period, and at least one day during said second time period, for example, before the start of the next treatment modality. The server can also be configured to receive a start date for the treatment regimen from the user's computer. The system may further comprise a user's computer (eg smart phone, etc.) away from the server to send a start date to the server in a network and receive notifications from the server in the network.
[031] These and other aspects of the present invention will be better understood by reference to the following detailed description and appended embodiments. BRIEF DESCRIPTION OF THE DRAWINGS
[032] Figure 1 is a plot of the amount of pro-collagen I as a function of treatment time in skin cells treated with (i) phytol alone (■) or (ii) retinol alone (▲) for 16 days. It is evident from Figure 1 that both retinol and phytol stagnate in effectiveness over time.
[033] Figure 2 is a plot of procollagen I production in cells treated with (i) phytol alone for 16 days, (ii) retinol alone for 16 days, (iii) retinol alone for 6 days followed by phytol alone for 10 days, (iv) phytol alone for 6 days followed by retinol alone for 10 days, as well as (v) untreated control cells.
[034] Figure 3 is a sample calendar of an embodiment of the invention that shows a possible rotational regime.
[035] Figures 4 and 5 are examples of packaging modalities of the present invention.
[036] Figure 6 is a flowchart of a method and system for notifying a user of a product according to the invention, which of the two treatment compositions should be used on a particular day.
[037] Figures 7 and 8 are examples of another packaging modality of the invention that has two reservoirs in a single container that are not separable from each other and which are each loaded with a composition for skin care different skin.
[038] Figures 9 to 11 are cross-sectional views of a packaging modality of the invention illustrating the operation of each pump to dispense a first cosmetic composition from the first reservoir using the first pump (Figure 10) and dispense a second cosmetic composition from a second reservoir using the second pump (Figure 11).
[039] Figures 12A and 12B illustrate embodiments of the invention in which two compositions are contained in separate reservoirs in a single container, in which the container is marked with an alphanumeric symbol that identifies each reservoir (in this case, "1" and "2 "). Figure 12A also has an identifier that indicates each day of the week visible on the outside of the container. Figure 12B illustrates a variant of the embodiment of Figure 12A in which a circular patch was placed on the day of the week the treatment regimen began (in this case, Monday or "S"). The packaging or label on the outside of the container may have different colors or patterns or other visible images to identify the reservoir 14 and 16, as indicated in Figures 12A and 12B by the different hatch marks.
[040] Figure 13 is a plot of the percentage change from a control in the amount of hyaluronic acid produced in human dermal fibroblasts when exposed to (A) a ten-day treatment of Tiliacora triandra hydroponic extract, (B ) a ten day treatment of niacinamide, (A+B) a ten day treatment of Tiliacora triandra and niacinamide, (B/A) a five day treatment of Tiliacora triandra followed by a five day treatment of niacinamide and (B/A) A five day treatment of niacinamide followed by a five day treatment of Tiliacora triandra. Columns marked with an "*" indicate statistical significance.
[041] Figure 14 is a plot of the percentage change from a control in the amount of hyaluronic acid produced in human dermal fibroblasts when exposed to (1) a ten-day treatment of retinol ("A"), (2) a ten day treatment of coleus ("B"), (3) a ten day treatment of retinol and coleus ("A+B"), (4) a five day treatment of retinol followed by a treatment of five days of coleus ("A/B") and (5) a five day treatment of coleus followed by a five day treatment of retinol ("B/A"). Columns marked with an "*" indicate statistical significance.
[042] Figure 15 is a plot of the percentage change from a control in the amount of hyaluronic acid produced in human dermal fibroblasts when exposed to (1) a ten-day treatment of niacinamide ("A"), (2) a ten day treatment of glycolic acid ("B"), (3) a ten day treatment of niacinamide and glycolic acid ("A+B"), (4) a five day treatment of niacinamide followed by a a five-day glycolic acid ("A/B") treatment and (5) a five-day glycolic acid treatment followed by a five-day niacinamide ("B/A") treatment. Columns marked with an "*" indicate statistical significance.
[043] Figure 16 is a plot of the percentage change from a control in the amount of hyaluronic acid produced in human dermal fibroblasts when exposed to (1) a ten-day KTFK ("A") treatment, (2) a ten-day treatment of Tiliacora triandra hydroponic ("B") extract, (3) a ten-day treatment of KTFK and Tiliacora triandra ("A+B"), (4) a five-day treatment of KTFK followed by a five day treatment of Tiliacora triandra ("A/B") and (5) a five day treatment of Tiliacora triandra followed by a five day treatment of KTFK ("B/A").
[044] Figure 17 is a plot of the percentage change from a control in the amount of hyaluronic acid produced in human dermal fibroblasts when exposed to (1) a ten-day treatment of glycolic acid ("A"), (2 ) a ten-day treatment of Tiliacora triandra hydroponic ("B") extract, (3) a ten-day treatment of glycolic acid and Tiliacora triandra ("A+B"), (4) a five-day treatment of Tiliacora triandra followed by a five day treatment of glycolic acid ("A/B") and (5) a five day treatment of glycolic acid followed by a five day treatment of Tiliacora triandra ("B/A"). Columns marked with an "*" indicate statistical significance.
[045] Figure 18 is a plot of the percentage change from a control in the amount of hyaluronic acid produced in full-thickness 3D models when exposed to (1) a ten-day treatment of glycolic acid ("A" ), (2) a ten-day treatment of Tiliacora triandra hydroponic ("B") extract, (3) a ten-day treatment of glycolic acid and Tiliacora triandra ("A+B"), (4) a treatment of five days of glycolic acid followed by a five day treatment of Tiliacora triandra ("A/B") and (5) a five day treatment of glycolic acid followed by a five day treatment of Tiliacora triandra ("B/A" ). Columns marked with an "*" indicate statistical significance.
[046] Figure 19 is a plot of the percentage change from a control in the amount of type I procollagen produced in human dermal fibroblasts when exposed to (1) a ten-day retinol ("A" treatment ), (2) a ten-day treatment of Coleus forskohlii ("B"), (3) a ten-day treatment of retinol and Coleus forskohlii ("A+B"), and (4) a five-day treatment of Coleus forskohlii followed by a five-day retinol ("B/A") treatment. Column marked with an "*" indicates statistical significance.
[047] Figure 20 is a plot of the percentage change from a control in the amount of type I procollagen produced in human dermal fibroblasts when exposed to (1) a ten-day phytol ("A" treatment ), (2) a ten day treatment of retinol ("B"), (3) a ten day treatment of phytol followed by a five day treatment of retinol ("A/B) and (4) a treatment of five days of retinol followed by a five day phytol treatment ("B/A"). Columns marked with an "*" indicate statistical significance. DETAILED DESCRIPTION OF THE INVENTION
[048] The detailed embodiments of the present invention are disclosed herein; however, it should be understood that the disclosed embodiments are merely illustrative of the invention which may be incorporated in various ways. Furthermore, each of the examples given in conjunction with the various embodiments of the invention is intended to be illustrative rather than restrictive. Therefore, the specific functional and structural details disclosed herein are not to be construed as limiting, but only as a representative basis for instructing a person skilled in the art to variously apply the present invention.
[049] All percentages given herein refer to the percentages by weight of a particular component in relation to the entire composition, including the vehicle, except where otherwise indicated. It will be understood that the sum of all % by weight of individual components within a composition will not exceed 100%. Except where otherwise indicated, any ingredient (including active and inactive ingredients) may be included in a composition in an amount from about 0.0001 to 50%, from 0.001 to 20%, from 0.01 to 10% or from 0.1 to 5% by weight of the composition.
[050] All terms in this document are intended to have their common meaning, except where provided otherwise. The phrase "physiologically acceptable" or "physiologically compatible" is used interchangeably with "cosmetically acceptable", "topically acceptable" and "dermatologically acceptable" and is intended to mean that a particular component is generally considered safe and non-toxic for application to a human integument (eg skin) at the levels used.
[051] The term "prevent", for use herein, includes delaying or slowing the onset of progression of a particular skin aging sign.
[052] The phrase "individual in need" refers to a human being who could benefit from improved dermal health or appearance, including male or female individuals. In some modalities, the individual who needs it is a female individual.
[053] The term "skin" includes, without limitation, the lips, facial skin, hands, arms, neck, scalp and chest. For use in the present invention, the term "consists essentially of" is intended to limit the invention to specified materials or steps and those that do not substantially affect the basic and innovative characteristics of the claimed invention, as understood from reading this descriptive report .
[054] The identification of a particular active agent as having a certain activity is not limiting, except where indicated otherwise, and does not prevent the same agent from having additional activities. For example, TDPA is listed herein as an "antioxidant", but it must also be a potent skin lightening agent. Similarly, hexylresorcinol is also identified herein as an "antioxidant", but is also known to have antimicrobial, antiseptic and anesthetic activity and is contemplated to be a skin lightening agent.
[055] Reference to "C2-20 esters" of active agents will be understood to include esters formed by C2-20 hydrocarbon alcohols with carboxylic acid groups in the present active agents or esters formed by C2-20 hydrocarbon carboxylic acids with alcohol groups in the present active agents. Similarly, "C2-20 amides" of active agents will be understood to include amides formed by C2-20 hydrocarbon amines with carboxylic acid groups in the present active agents or amides formed by C2-20 hydrocarbon carboxylic acids with groups amine in the present active agents. The C2-20 esters and amides include, without limitation, C2-6 esters and amides, C7-11 esters and amides, and C12-20 esters and amides. Hydrocarbons can be aliphatic, aromatic or partially aromatic and aliphatic. Hydrocarbons can be saturated or contain one or more unsaturated (eg, olefinic) bonds. In some embodiments, the C2-20 esters or amides can be acetyl, propyl, lauryl, palmitate, palmitoyl, etc. In some embodiments, the "C2-20 esters or amides" comprise a straight-chain aliphatic C16 hydrocarbon. The present invention encompasses the use of all C2-20 esters of all active agents described herein that have derivable carboxylic acid or hydroxyl functionalities. The invention also encompasses the use of all C2-20 amides of all active agents described herein that have derivable (i.e., reactive) carboxylic acid or starch functionalities.
[056] The invention also encompasses physiologically acceptable salts (eg acid addition salts, carboxylate salts, etc.) of any of the active ingredients identified herein. The salts of the compounds which can be used according to the invention can be chosen from alkali metal or alkaline earth salts or from strontium, zinc or magnesium salts, salts of an organic amine or quaternary ammonium salts. The salts of the compounds according to the invention can be chosen from salts of a mineral or organic acid, in particular hydrochlorides, hydrobromides or citrates.
[057] In some embodiments of the present invention, at least two separate compositions are provided, each differing in terms of identity or amount of at least one active ingredient. The active agent ("skin care active ingredient") will typically be dispersed or dissolved in a physiologically acceptable carrier (diluent or vehicle). In various embodiments, any of the topical compositions of the invention (including the first and/or second, etc.) can comprise an effective amount of one of the following:
[058] Retinoids, including Retinol and its C2-36 esters (eg, acetate, palmitate);
[059] Ascorbic acid and its salts and C2-36 esters (eg palmitate, tetrahexyldecyl, etc.)
[060] Tocopherol and its C2-36 esters (eg tocopherol acetate);
[061] Glycolic acid and its salts (eg ammonium or sodium glycolate) or C2-36 esters;
[062] Lactic acid and its salts (ammonium or sodium lactate) or C2-36 esters (eg myristyl);
[063] Hexylrescorcinol;
[064] Niacinamide;
[065] Thiopropionic acid and its salts and C2-36 esters (eg, mono and di-lauryl);
[066] Fitol and its C2-36 esters;
[067] Peptides (eg hydrolyzed wheat gluten, hydrolyzed rice protein, tetrapeptide-4, etc.)
[068] Palmitoyl oligopeptides (eg palmitoyl tetrapeptides, palmitoyl pentapeptides, etc.)
[069] Palmitoyl lysyl aminovaleroyl lysine (KavaK);
[070] Ceramides (for example ceramide-2);
[071] L-4-thiazolylalanine;
[072] Cys-6-nonenol;
[073] N-Acetyl amino acids (eg, N-Acetyl Tyrosinamide);
[074] Mesyloxybenzyl isobutylbenzene sulfonamide;
[075] Cinnamido benzylpiperidinyl ethoxypropylbenzamide;
[076] Caffeine;
[077] Hyaluronic acid and salts (eg, sodium hyaluronate) and
[078] Salicylic acid and derivatives (eg C2-36 esters) thereof.
[079] In some embodiments, any of the compositions of the invention (for example, the first, second, etc.) may comprise one or more of: Acetyl Hexapeptide-3, Acetyl Trifluoromethylphenyl Valyl-Glycine, Acetyl Tyrosinamide, Adenosine, Allantoin, All-Trans Retinoic Acid, Alpha Lipoic Acid, Alpha-Isomethyl Io-None, Amino Acids (Arginine, Glutamate, Glycine, Lysine, Etc.), Ammonium Glycolate, Apigenin, Arabinogalactan, Ascorbic Acid, Ascorbyl Glycoside, Ascorbyl Palmitate , Aspartic Acid, Astaxanthin, Atelocollagen, Azulene, Beta-Glucans, Bio-Flavonoids, Biosaccharide Gum 1, Biotin, Butylphenyl Methylpropional, Caffeine, Calcium Pantetheine Sulphonate, Calcium Pantothenate, Carnitine, Carnosine, Ceramide-2, Chlorphenesine , Cinamido Benzylpiperidinyl Ethoxypropylbenzamide, Cis-6-Nenol, Citral, Citronellol, Colloidal Platinum, Copper Peptides, Coumarin, Daidzein, DHT (Dihydrotestosterone or 5α-Dihydrotestosterone), Dilauryl Thiodipropionate, Dimeti lethanolamine (DMEA), Disodium Stearoyl Glutamate, Dithiolane-3-Pentanic Acid, Ellagic Acid, Eugenol, Farnesyl Acetate, Ferrulic Acid and Derivatives (Ethyl Ferrulate, Sodium Ferrulate, etc.), Finasteride, Galactoarabinan, Acid Gamma-Amino Butyric (GABA), Genistein, Geraniol, Glycosamine, Glutamine, Glutathione, Soy Glycine Oil, Glycolic Acid, Hexamidine, Hexapeptide-2, Hexylrescorcinol, HGH Releasers, Hyaluronic Acid (HA) and Salts, Protein Hydrolyzed Rice, Hydrolyzed Soy Protein, Hydrolyzed Wheat Gluten, Hydrolyzed Wheat Protein, Hydroquinone, Hydroxyethylpiperazine Ethane Sulphonic Acid, Hydroxy-isohexyl 3-Cyclohexene Carboxaldehyde, 6-Hydroxy-2.5 Acid ,7, Tetramethylchroman-2-carboxylic, Idebenone, Isoeugenol, Latanoprost, Limonene, Linalool, Lysine Carboxymethyl Cysteinate, Tetrapeptides (eg, Lys-Thr-Phe-Lys), Lysyl Aminovaleroyl Lysine, Ascorbyl (magnesium phosphate, Malachite antioxidant extract), Mesiloxybenzyl Isobutylbenzene Sulfonamide, Minoxidil, N-Hydroxysuccinimide, Niacinamide, Nonenol, Oryzanol, Oxothiazolidinecarboxylic Acid, Palmitoyl Lysyl Aminovaleroyl Lysine (Kavak), Palmitoyl Oligopeptide, Palmitoyl Pentapeptide (Matrixyl), Tetrapeptide, Pentapeptide-3 of Palmitoyl, Palmitoyl Tetrapeptide-7, Palmitoyl Tetrapeptide-10, Panthenol, Pantethine Triacetate, Pentaerythryl tetra-di-t-Butyl Hydroxyhydrocinnamate, Phloretin, Phytol, Phytosterols, Pichia peptone filtrate, Polyphenol antioxidants, Propolis, Picnogenol, Pyridoxine Hydrochloride, Quercetin, Resveratrol, Retinaldehyde, Retinoic Acid, Retinol, Retinyl Palmitate, Royal Jelly, Rutin, Saccharide Isomerate, Salicylic Acid, Salicyloyl Phytosphingosine, Sodium Chondroitin Sulfate, Sodium Hyaluronate, , Sphingolipids, Sphingosine, Sugar Amines, Superoxide Dismutase, Tetrahexidecyl Ascorbate, Tetrapeptide-4, Thiazolylala Nin, Thiodipropionic Acid, Tocopherol, Tocopheryl Acetate, Tretinoin, Trioxaundecanedioic Acid, Ubiquinone (Co Q10), Vitamin A, Vitamin B3, Vitamin E (Tocopherol), Ximeninic Acid, Zinc and Zinc Pyrithione.
[080] In some embodiments, a composition comprises a C20-C25 terpene alcohol (eg phytol) or a metabolite thereof formed in human tissues (eg phytanic acid). In some embodiments, a composition comprises a retinoid (e.g., vitamin A, retinol, retinyl acetate, retinyl, propionate, retinyl palmitate, rentin-A, retinoic acid, retinaldehyde, etc.).
[081] In some embodiments, the first and second compositions will differ in relation to the presence or amount of at least one active component. In some embodiments, however, the first and second compositions may comprise the same amount of an active agent, other differences between them (eg, differences in identity or amount of another active agent) are provided.
[082] In some embodiments, at least one composition (eg, the first composition) may comprise retinol (or an ester), and the second composition may be free or essentially free of retinol (or an ester), which means that it comprises less than an effective amount, or comprises an amount of retinol (or an ester) that is greater or less than the amount contained in the first composition.
[083] The two different compositions form the basis of two different treatment modalities, each of which is carried out for a limited period of time, typically a predetermined period of time, after which the other treatment is carried out for a period of time. time-limited, typically predetermined. This process can be repeated any number of times to improve the health and appearance of human skin, while ideally overcoming or lessening the impact of the sensitization or tolerance phenomenon that develops with the active ingredient of skin care, including retinoid treatment. and/or phytol. The process can also be implemented with three, four, five, six or seven (or more) different compositions in a similar way.
[084] Without wishing to be bound by any theory, methods according to some embodiments of the present invention are believed to provide multiple skin care benefits through activation of retinoid X receptors (RXRs), receptor activated by peroxisome proliferator (PPAR) and/or retinoic acid receptors RARs. Activation of these receptors and responsive genes stimulate cell functions in multiple skin components, such as the epidermis, dermis, sebaceous glands, melanocytes, Langerhan cells and hair follicles, while alternate application allows for resensitization. In some embodiments, active agents, including a retinoid (eg, retinol) and a C20-C25 terpene alcohol (eg, phytol) or a metabolite thereof formed in human tissues (eg, phytanic acid), share by minus one common mechanism of action, including, without limitation, activity on RXRs, PPARs and/or RARs.
[085] Phytol and its derivatives (for example, ethers and C1-20 esters) belong to the class of compounds that can be called C20-C25 terpene alcohols. The phytol derivatives of the invention may conform to the structural formulas given in the document under No. WO 2001/066080 and U.S. Patent No. 7.960,437, the disclosures of which are incorporated herein by reference. Phytanic acid is also contemplated as a useful phytol derivative. Suitable phytol derivatives include, without limitation, C1-20 hydrocarbon esters from the esterification of phytol with a C1-20 carboxylic acid, or C1-20 hydrocarbon esters from the esterification of phytanic acid with an alcohol of C1-20 hydrocarbon. The invention encompasses the use of phytol, as well as phytol derivatives (esters, ethers, etc.), phytol precursors and phytol metabolites (including phytanic acid). Phytol metabolic precursors are compounds from which phytol can be formed through the action of enzymes present in human tissues, particularly skin. Phytol metabolites are compounds formed through the action of enzymes present in human tissues, particularly skin, on phytol.
[086] In some embodiments, a composition of the present invention will comprise phytol, for example, in an amount of from about 0.001 percent by weight (% by weight) to about 10% by weight based on the total weight of the composition. Typically, phytol may be present in an amount of from about 0.01% by weight to about 5% by weight, and more typically about 0.1% by weight to about 1% by weight, based on the total weight. of makeup.
[087] The term "retinoid" includes: (1) retinol; (2) retinol esters with carboxylic acids of 1 to 24 carbon atoms, such as retinyl acetate, retinyl propionate, retinyl butyrate, retinyl octanoate, retinyl laurate, retinyl palmitate, retinyl oleate, retinyl linoleate retinyl and the like; (3) retinol esters which have an alpha-hydroxy carboxylic acid; (4) retinol ether derivatives, including C 1-24 alkyl ether, ethers derived from glycolic acid, as well as amide and glycolate ester such as retinyl glycolyl ether; (5) retinaldehyde; (6) retinoic acid; (7) retinoic acid esters with alcohols of 1 to 24 carbon atoms; (8) isotretinoin, as well as synthetic retinoid imitations, and derivatives of those mentioned above, as well as others that bind to RAR receptors; (9) cis- and trans-isomers of the retinoids mentioned above; (10) salts of the aforementioned retinoids; and (11) mixtures of any of the aforementioned compounds. A preferred retinoid for use in a composition in accordance with the present invention is retinol, including the cis- or trans-isomer of retinol, typically the trans-isomer.
[088] In some embodiments, a composition of the invention may comprise a retinoid (eg, retinol) in an amount from about 0.001% by weight to about 10% by weight based on the total weight of the composition. Typically, the retinoid (e.g., retinol) is present in an amount of from about 0.01% by weight to about 5% by weight, or about 0.1% by weight to about 2.5% by weight , based on the total weight of the composition. The amount of retinoid can be adjusted, based on the potency of the retinoid, without departing from the present invention.
[089] The invention provides methods that improve and/or sustain skin health and/or improve the appearance of one or more signs of dermatological aging when topically applied to human integuments (skin, lips, nails, hair, etc. ), particularly skin such as facial skin. In some embodiments, at least two separate compositions, wherein one composition has an antioxidant, such as a C20-C25 terpene alcohol (eg, phytol), and the other composition has a different skin care active ingredient, as a retinoid (eg, retinol), are applied topically to the same area of skin in a sequential, rotary, or alternating fashion.
[090] The two or more treatment modalities will typically comprise: (1) topical application (typically at least once daily) of a first composition comprising a first active ingredient during a first period of time, and (2) topically (typically, at least once daily) applying a second composition comprising a second active ingredient for a second period of time, and (3) optionally repeating steps (1) and (2) one or more times. The first and second compositions may comprise at least one active ingredient that is different from the other, or is present in a different amount. In some embodiments, the first composition comprises phytol. In some embodiments, the second composition comprises phytol. In some embodiments, the first composition comprises retinol. In some modalities, the second composition comprises retinol. In some embodiments, the first composition comprises phytol and the second composition does not comprise phytol or comprises phytol in an amount less than the first composition. In some embodiments, the first composition comprises retinol and the second composition does not comprise retinol or comprises retinol in an amount less than the first composition. In some embodiments, the second composition comprises phytol and the first composition does not comprise phytol or comprises phytol in an amount less than the second composition. In some embodiments, the second composition comprises retinol and the first composition does not comprise retinol or comprises retinol in an amount less than the second composition.
[091] In some embodiments, the first composition is applied topically to the skin at least once a day (eg, once, twice or three times a day, etc.) for a time period of about 1 to 31 days (or from 1 to 5 days), from about 3 to 20 days, or from about 5 to 10 days, or for about a week. In some embodiments, the second composition is topically applied to the same area of skin at least once a day (e.g., once, twice or three times a day, etc.) for a time period of about 1 to 31 days (or from 1 to 5 days), from about 3 to 20 days, from about 5 to 10 days, or for about a week. In some embodiments, treatment with the second composition will begin after a predetermined time after the end of the first period of time, including, on the following day, or after two, three or more days (e.g., after five days or one week) , during such time the individual may optionally receive no treatment or may receive different treatment from the first and second compositions. In some embodiments, treatment with the first composition will begin after a predetermined time after the end of the second period of time, including, on the following day, or after two, three or more days (e.g., after one week), during such time the subject may optionally receive no treatment or may receive different treatment from the first and second compositions. In some embodiments, treatment with the second composition will begin the day after the end of the first time period. In some embodiments, treatment with the first composition will begin the day after the end of the second time period. In several modalities, the treatment protocol will comprise the following: AB, ABA, ABAB, ABABA or ABABAB, etc. In several modalities, the treatment protocol will comprise the following: BA, BAB, BABA, BABAB, BABABA, etc., where "A" represents the first treatment period with the first composition and "B" represents the second treatment period with the second composition. Treatments can be continued until a skin benefit is observed or longer. The treatment protocol can be represented as (AB)n+1 or (BA)n+1, where "n" is an integer indicating the number of times the method is repeated. For example, "n" can be 1, 2, 3 and so on, up to 100 or more. Referring now to Figure 3, a schedule for a first possible treatment period "A" and a second possible treatment period "B" is shown. In this modality, the treatment period "A" is 7 days in duration and the treatment period "B" is 7 days in duration. In another embodiment, treatment period "A" is 5 days in duration and treatment period "B" is 2 days in duration.
[092] In some embodiments of the invention, a third treatment modality, such as the topical application of a composition comprising an active agent different from said first and second compositions, can also be employed in sequence with the first and the second treatment modalities. The third composition can be applied at least once a day for a third period of time according to the criteria described above. In several modalities, the treatment protocol will comprise the following: ABC, ABCA, ABCAB, ABCABC, etc. and all permutations thereof, where "A" represents the first treatment period with the first treatment modality, "B" represents the second treatment period with the second treatment modality, and "C" represents the third protocol of treatment with the third treatment modality. There is essentially no limit to the number of treatment modalities that can be employed, or the combination/permutation of orders in which these treatment modalities are employed. For example, the treatment may comprise two, three, four, five, six, seven or more different treatments, each typically being employed at least once a day for a period from 1 to 31 days.
[093] In some embodiments, any of the compositions of the invention may comprise any active ingredient for the treatment of human skin. In some embodiments, any composition of the invention may be free of any active ingredient for the treatment of human skin that is present in another of the compositions of the invention. In some embodiments, any of the compositions may include (or may be free of) an active ingredient selected from glycolic acid (and salts thereof), thiodipropionic acid (TDPA) or esters thereof (eg, mono alcohol esters). and di-lauryl), hexylrecorcinol, niacinamide, or a botanical extract from a plant of the genus Eclipta (eg, Eclipta prostrata), Portulaca (eg, Portulaca grandiflora), Tiliacora (eg, Tiliacora triandra ) or Melicope (eg Melicope hayesii and/or Melicope ellyarana), etc. In some embodiments, the active ingredient will activate retinoid X receptors (RXRs), peroxisome proliferator activated receptor (PPAR) and/or retinoic acid receptors RARs. In some modalities, the active ingredient will not activate retinoid X receptors (RXRs), peroxisome proliferator activated receptor (PPAR) and/or retinoic acid receptors RARs.
[094] In some embodiments, the compositions of the invention (for example, the first and/or the second compositions, etc.) will comprise a biological extract. The extract can be an extract from a plant, yeast, fungus, etc. The extract can be from the roots and/or aerial portions of a plant, including, without limitation, the stems, twigs, bark, leaves, flowers, seeds, roots, fruit, rhizomes, vines, etc. Other biological materials, such as honey, can also be useful. Extracts include crushed or pulverized plant materials, as well as yeasts, lysates and isolates. Without limiting the invention, extracts from the following are contemplated as useful:
[095] Abies pindrow, Abrus fruticulosus, Abutilon indicum, Açaí, Acacia ca-techu, Acacia dealbata, Acacia melanoxylon, Acer Saccharinum, Acer Saccharum (Acer), acidopholus, aesculus, Aesculus hippocastanum seed , agaricus, agave, agrimonia, algae, Alisma orientale, Allamanda cathartica, almond, aloe, Aloe barbadensis leaf juice, Alpinia galanga leaf, Amomum melegueta, Amorphophallus campanulatus (rhizome/root), Ananas sativus (pineapple) fruit Anogeissus latifolia, Anthemis nobilis (flower), Anti-desma bunis, apple extract, apricot kernel, Aradirachta indica, Archidendron clypearia, Arctostaphylos viscida, Argania spinosa, Argania spinosa kernel, Aribodopsis Thaliana, Arnica flower, Ascophyllum Nodosum , Asmunda japonica, Asparagopsis, Atriplex portulacoides, Averrhoa carambola, Azadirachta indica (Neem), Basella alba, Bearberry, Bearberry extract, Berchemia lineata (leaf), Beta vulgaris, yeast lysate Bifida, birch bark extract, bitter orange blossom, St. Kitt's wort (Cimicifuga racemosa), black honey, black tea yeast, Boswellia serrata, brassica, Brassica Napus, Breynia fruticosa, Bupleurum falcatum root , Butea frondosa, Butea monosperma, Butyrospermum Parkii butter, Caesalpinia sappan Linn, Calatropis gigantean, Calendula officinalis, Callistephus chinensis, Calotropis gigantea, Camelina sativa, Camellia oleifera leaf, Camellia sinorasina leaf, Olesidora- munica, Cananga olesi- of Capsicum frutescens, Carica papaya fruit (papaya), carrot, cashew, Castanea sativa, Cayratia japonica, cedar, Cedrelopsis strikei, Cedrus deodara, Celosia argenta, Centella asiatica, Ceratonia siliqua (carob), Cereus grandiflorus flower (cactus), Chalara microspora, chamomile, Chamomilla recutita flower (matricaria), chestnut seed, Chlorella vulgaris, Chondrus crispus, Cimicifuga racemosa root, cinnamon, Cistanche tubulosa, Cistus ladanifer us L., Citronella, Citrus aurantium, Citrus aurantium dulcis fruit (orange), Citrus aurantium dulcis bark, Citrus Limon fruit (lemon), Citrus Medica Limonum, Citrus Reticulata bark, Clerodendron fragrans, Clerodendron lindleyi, Clerodendrum floribundum, Clinacanthus nutans, Clintonia borealis, Clitoria ternatea Linn extract, clove flower, Coccinia grandis, Cocculus glaucescens, Cocos nucifera (coconut) fruit juice, Coffea arabica seed (coffee), cola, Cola nitida seed, comfrey, Coleus forskohlii', Commersonia bartramia, Commiphom, Copernicia cerifera cera, Corallina officinalis, Crata-egus monogyna fruit, Crithmum maritimum, saffron flower, cucumber, Cucumis sativus fruit (cucumber), Curcuma longa, Curcuma cymbogonthorrh Cymbopogon nardus, Daucus carota sativa root (carrot), Dendranthema indicum, Derris scandens, Desmanthus illinoensis, Dianella ensifolia, Dodonaea petiolaris, Dodonaea viscosa, Duboisa myoporoides, Eclipta prostrata, Edelweiss, Ehretia acuminate, Emblica officinalis, English lavender, Eperua falcata bark, Equisetum arvense, Equisetum Arvense (horsetail), Eremophila mitchelli, Erthrina flabelliformis, Erythina indica, Erythrina flabelliformis, Erythrina flabelliformis, Erythrina flabelliformis, Erythrina groffenia, Erythrina indica Evening primrose oil, Evernia furfuracea, Evernia prunastri, Eypassordtia polistachya wood (Palo Azul), Fagus sylvatica, fenugreek seed, Fibraretinum resica Pierre, Ficus benghalensis, Ficus coronata, fir needle (Abies al-ba ), fruit of Foeniculum vulgare (fennel), forskohlii, Fructus Mume, geranium, Ginkgo biloba, Glochidium wallichianum, Glycine soybean (soybean), Glycyrrhiza glabra, Gomphrena globosa Linn, Goodenia ovata, Gracilaria textorii, green tea, Gryfollnos frondosa, Gymtaphyllnos frondosa , Gynandropsis gynandra, Haberlea rhodopensis, Hamamelis viginiana, Hawthorn, Hedyotis hedyotidea, Helianthus Annuus, Helianthus annuus seed (sunflower), Helichrysum gymnoce phalum, Helichrysum odoratissimum, Heliotropium indicum, hibiscus flower, Hibiscus sabdriffa, holly (Ilex), honey, Hordeum vulgare, Hoya carnosa, Humulus japonicus, Humulus lupulus, Humulus scandens, Hibiscus esculentus hidrolysado, Ulva lactum Hypericum performatum, Ilex paraguariensis leaf, Ilex purpurea Hassk, Innula racemosa, Ixora chinensis, Japanese bamboo (Fallopia japonica), Jasminum offi-cinale, Jasminum sambac extract, Jojoba seed, Jugans regia, Juniperus oxycedrus, Justzea ventricosa, , blue carolina (Thunbergia laurifloria), Lavandina, Lavandula angustifolia (lavender), Lavandula hybrida, Lavatera ple-beian, lavender, Lens esculenta seed, Lentinus edodes, Leptospermum lanigerum, licorice, Ligusticum chiangxiongum, Ligusticum chiangxiong, Ligusticum capassa, Loropetalum chinense, Lycium barbarium (goji), Macrocycstis pyrifera, Maesa japonica, Mallotus philippinensis, Malus domest fruit cell culture ica, Mammea siamensis, Manuka honey, marjoram (leaf), Matricaria (flower), Medemia nobilis, Medicago sativa (alfalfa), Melaleuca quinquernervia, Melicope hayesii, Melicpoe ellyarana, Melissa officinalis, Melissa officinalis (leaf), Menyanthes trifoliata, Mi-mosa tenuiflora husk, Mimusops elengi, Morinda citrifolia, Moringa oleifera, Moringa pterygosperma, Morus Nigra, mucor miehei mushroom, black corn biomass MycoFusions Coriolus, barley biomass without waxy husk MycoFusions Mai- tarzetta, Narcissus crenulata, Nerium indicum, Nigella sativa (seed), Norwegian spruce, Oenothera biennis oil, Olea europaea (olive) (leaf), Olisma orientale extract, olive, Omolanthes populifolius, Operculina turpethum, Ophiopogon Thunb. PE, orange peel, Origanum heracleoticum flower, Origanum majo-rana (leaf), Orthosiphon grandiflorus, Oryza (rice) sativa, Ozothamnus obcordatus, Padina pavonica, palm nut, Palmaria palmata, Panax ginseng root, Pancra-tium maritimum , Passiflora edulis (seed), Passiflora incarnata flower, Pecan, Pelargonium graveolens flower, Pelvetia canaliculata, Perilla, Perilla ocymoides oil (seed), Phaeodactylum tricornutum, Phyllanthus acidus, Phyllanthus emblica fruit, Phronyllarthus , pine needles, Piper betel, Pi-per nigrum, Pisum sativum (pea), plankton, Plumbago indica, Plumeria acuminata, Polyanthes tuberosa, Polygonum Cuspidatum, pomegranate, Populus nigra, Portulaca oleracea, Portulaca sativa, Pouzolzia pentandra from Prunus amygdalus dulcis (sweet almond), Prunus armeniaca (stone), Psoralea corylifolia, Pteris semipinnata, Pueraria lobata symbiosome, Punica granatum fruit, Pygeum (Prunus) africanum, Pyrus malus, Pyrus malus root (apple), Radix platycodonis, Raphia farinifera, Rhinacanthus nasutus, Rhizophora mangle bark, rice bran oil, Roman chamomile, Rosa canina fruit, rose flower, rosemary (flower), Rosmarinus offi- cinalis, royal jelly, Rubies, Rubus ideas (raspberry extract), Rumex crispus, Saccharomyces cerevisiae, Saccharum officinarum (sugar cane), Salix nigra, Salvia officinalis, Salvia Sclarea, Sambucus chinensis, Sapindus rarek (fruit), Sargassum muticum, Sativa bran oil, Saxifraga sarmentosa, Scenedesmus, Scoparis dulcis, Scutellaria baicalensis root, sea buckthorn, Sedum sarmentosum bunge, seaweed, Selaginella tamariscina, Serrisa japonica, Sesbania aculeata, Sesbania grandiegeia (flower) of silver birch bark, Silybum marianum (fruit), Simmondsia chinensis, Sophora tomentosa, spruce needles, Stellaria medica (L.) cry., Stenoloma chusana, Stephania rotunda, Stephania solid, giraffe seed ssol, Symphytum officinale, Tagetes erecta Linn, Terminalia bellerica, Tetracera asiatica, Theobroma cacao, Thermus thermophillus yeast, Thermus thermophilus, Thuja, Thunbergia laurifolia, Tilia cordata wood, Tilia platyphyllos, Tiliacora triandra tomato, glycolipid , Triticum vulgare germ (wheat), turmeric root, Uncaria gambir, Vaccinium macrocarpon (cranberry), Vaccinium myrtillus fruit/leaf, Vernonia cinerea, Vigna aconitifolia, Vitis vinifera fruit (grape), Voandzeia subterranea, walnut, water lily, willow (bark), Withania somniferia, yohimbine, Zanthoxylum nitidium, Zea mays seed (corn) and Zingiber cassumunar Roxb.
[096] In the above list of botanical/biological extracts, the part of the plant indicated in parentheses or otherwise represents a non-limiting modality. It will be understood that the invention encompasses extracts from any portion of the aforementioned plants and organisms. Furthermore, the particular species indicated are also merely representative of certain modalities, and in each case, the invention encompasses extracts from any species within the genus. In other words, the revelation of Melicope hayesii, for example, will be understood to include extracts from the species Melicope hayesii, as well as extracts from any species within the genus Melicope.
[097] Extracts can be prepared by solvent extraction, steam distillation or any other method known in the art. In some embodiments, at least one of the topical compositions of the invention comprises an extract, obtained by steam distillation, of any of the aforementioned biological materials and plants (each being considered a distinct embodiment). In some embodiments, at least one of the topical compositions of the invention comprises an extract, obtained by extracting with water (e.g., basic, neutral or acidic), from any of the aforementioned biological materials and plants (each being one considered a distinct modality). The extraction water may also include a water miscible co-solvent including lower alcohols (eg C1-6) such as methanol, ethanol, isopropanol, propanol, butanol, etc. (typically, ethanol). In some embodiments, at least one of the topical compositions of the invention comprises an extract, obtained by extraction with a solvent system comprising from about 5 to 95% (v/v), 10 to 90% (v/v), 20 to 80% (v/v), 40 to 60% (v/v) water (eg, basic, neutral or acidic) and about 5 to 95% (v/v), 10 to 90% (v /v), 20 to 80% (v/v) or 40 to 60% (v/v) of ethanol, of any of the aforementioned biological materials and plants (each considered a distinct modality). In some embodiments, at least one of the topical compositions of the invention comprises an extract, obtained by extraction with an organic solvent (for example, non-polar, polar aprotic or polar protic), from any of the biological materials and plants mentioned above (each considered a distinct modality). Suitable solvents include hexane and other C1-12 or C5-8 hydrocarbons, lower alcohols, C2-16 ethers (for example diethyl ether), C3-12 esters (for example ethyl acetate), C2-12 (for example , acetone, butanone, etc.), carbon dioxide (liquid or supercritical), etc. Biological extracts can be dried in vacuum or atmospheric pressure to remove water and extraction solvents. Biological extracts can be dried using lyophilization. Biological extracts can be passed over charcoal or activated charcoal and/or passed through filters and/or microfilters to remove bacteria and other biological materials.
[098] Typically, the treatment regimen of the invention is repeated for a period of time sufficient to improve skin health and/or obtain a desired benefit of decreasing signs of aging in the skin (e.g., reduction in number or severity of wrinkles and/or expression lines, or improved elasticity and/or decreased sagging, etc.). This may entail treatment (eg topical application of compositions) at least once a day for at least one week, at least two weeks, at least four weeks, or at least eight weeks or more. In some embodiments, compositions are applied directly to a specific location on the skin (ie, directly over a wrinkle and/or expression line, under the eyes, on a blemish, etc.). In some embodiments, the first and/or second and/or third compositions will be applied to the skin in an amount from about 0.001 to about 100 mg/cm2, more typically from about 0.01 to about 20 mg/cm2 or from about 0.1 to about 10 mg/cm2.
[099] Although the compositions and methods of the invention are contemplated as useful for the treatment (i.e., reduction, mitigation, amelioration, relief, impediment, deceleration, correction and/or elimination) of aging (chronological) dermatological effects , hormonal or photoaging) and/or environmental stress are also suitable for use in the treatment of other dermatological skin conditions, including, without limitation, unwanted or excessive pigmentation. Numerous areas of the body can be treated, including, without limitation, the face, forehead, lips, scalp, neck, arms, hands, legs, knees, feet, chest, back, groin, buttocks, thighs and the like. In some embodiments, the compositions are applied to the face, lips, chest, arms and/or hands, particularly the face.
[0100] The cosmetically acceptable carrier or vehicle may be in the form of an emulsion. Non-limiting examples of suitable emulsions include water-in-oil emulsions, oil-in-water emulsions, silicone-in-water emulsions, water-in-silicone emulsions, wax-in-water emulsions, triple water-oil emulsions -water or similar that have the appearance of a cream, gel or microemulsions. For use herein, the term "oil" includes silicone oils, except where otherwise noted. The emulsion may include an emulsifier, such as a nonionic, anionic or amphoteric surfactant, or a gelling agent, typically in an amount of from about 0.001% to about 5% by weight.
[0101]The cosmetically acceptable vehicle may include water; vegetable oils; mineral oils; ester oils such as octal palmitate, isopropyl myristate, isopropyl palmitate; ethers such as dicapryl ether and dimethyl isosorbide; alcohols such as ethanol and isopropanol; fatty alcohols such as cetyl alcohol, cetearyl alcohol, stearyl alcohol and behenyl alcohol; isoparaffins such as isooctane, isododecane (IDD) and isohexadecane; silicone oils such as cyclomethicone, dimethicone, dimethicone cross polymer, polysiloxanes and their derivatives, preferably organomodified derivatives including PDMS, dimethicone copolyol, dimethiconols and amodimethiconols; hydrocarbon oils such as mineral oil, petrolatum, isoeicosane and polyolefins, for example polyisobutene (hydrogenated); polyols such as propylene glycol, glycerin, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol; waxes such as beeswax, carnauba, ozokerite, microcrystalline wax, polyethylene wax and botanical waxes; or any combinations or mixtures of those mentioned above. Aqueous vehicles, including serums, can include one or more water miscible solvents, including lower alcohols such as ethanol, isopropanol and the like. The vehicle can comprise from about 25% to about 99.9% by weight of the composition.
[0102] In one embodiment of the invention, any of the compositions may include additional skin actives, including, but not limited to, retinoids, botanicals, keratolytic agents, desquamation agents, keratinocyte proliferation enhancers , collagenase inhibitors, elastase inhibitors, 5-alpha reductase inhibitors, depigmenting agents, anti-inflammatory agents, steroids, anti-acne agents, antioxidants, and advanced glycosylation end product (AGE) inhibitors, to name a few. The amounts of these various ingredients are those conventionally used in the cosmetic field to achieve their intended purpose, and range individually or collectively typically from about 0.001% by weight to about 20% by weight of the composition. The nature of these ingredients and their amounts need to be compatible with the function of the developing compositions.
[0103]Exemplary antiaging components include, without limitation, botanicals (eg Butea frondosa extract, Tiliacora triandra extract, Portulaca oleracea, Melicope elyarana, etc.); hydroxy acids (including alpha-hydroxy acids and beta-hydroxy acids), salicylic acid and alkyl salicylates; exfoliating agents (eg glycolic acid, 3,6,9-trioxaundecanedioic acid, etc.), estrogen synthetase stimulating compounds (eg caffeine and derivatives); compounds with the ability to inhibit 5-alpha-reductase activity (eg, linolenic acid, linoleic acid, finasteride and mixtures thereof); and barrier function enhancing agents (eg, ceramides, glycerides, cholesterol and its esters, alpha-hydroxy and omega-hydroxy fatty acids and esters thereof, etc.), to name a few.
[0104]Exemplary retinoids include, without limitation, retinoic acid (eg, all trans, 9-cis, or 13-cis), and derivatives thereof, retinalaldehyde, retinol (Vitamin A) and esters thereof such as palmitate of retinyl, retinyl acetate and retinyl propionate and salts thereof. Particular mention can be made of retinol. When present, retinoids will typically be included in amounts of from about 0.0001% to about 5% by weight, more typically from about 0.01% to about 2.5% by weight, or from about 0.1% to about 1.0% by weight. Compositions in accordance with this embodiment will typically include an antioxidant such as ascorbic acid and/or BHT and/or a chelating agent such as EDTA or a salt thereof (e.g., disodium EDTA).
[0105] In another embodiment, the topical compositions of the present invention may also include one or more of the following: a skin penetration enhancer; an emollient such as isopropyl myristate, petrolatum, volatile or non-volatile silicone oils (eg, methicone, dimethicone), ester oils, mineral oils, and fatty acid esters; a humectant such as glycerin, hexylene glycol or caprylyl glycol; a skin toner such as palmitoyl oligopeptide, collagen, collagen enhancing agents, and/or glycosamino glycan (GAG); a sunscreen such as avobenzone or octyl methoxycinnamate; an exfoliating agent; and an antioxidant.
[0106] Suitable tyrosinase inhibitors include thiodipropionic acid; hydroquinone; kojic acid; and others listed elsewhere in this application. Some depigmentation agents or skin lighteners act as inhibitors of tyrosinase, an enzyme that has its catalytically active domain within the organ- els known as melanosomes. Tyrosinase converts phenols, including tyrosine, into ortho-quinones which are subsequently converted to melanin within melanosomes.
Suitable melanin inhibitors include niacinamide serine protease inhibitors; and others listed elsewhere in this application. These can act by interrupting the transfer of melanosomes from melanocytes to keratinocytes.
[0108] Suitable glycosamino glycan (GAG) enhancing agents include, for example, phytol; terpene alcohols; peptides; PPAR modulators; and/or botanical products; and/or others listed elsewhere in this application. Glycosamino glycans (GAGs) are produced by the body to maintain structural integrity in tissues and to maintain fluid balance. GAGs serve as a natural moisturizer and lubricant between epidermal cells to inhibit the production of matrix metalloproteinases (MMPs) - enzymes activated by UV exposure or inflammation that contribute to collagen breakdown while inhibiting the formation of new collagen . Topical GAG stimulants, GAG supplements and/or MMP inhibitors can help provide temporary restoration of enzyme balance to slow down or prevent matrix disruption and consequent onset of wrinkle formation.
[0109] Suitable collagen enhancing agents include retinoids; peptides; botanical products; and others listed elsewhere in this application. Collagen and elastin are the main components of the dermis-epidermal junction (DEJ), that is, a specialized structure that mediates close contact between the lamina dense (the basement membrane zone between the epidermis and dermis of the skin) and the underlying connective tissue of the dermis. The dermis-epidermal junction (DEJ) includes interlocking finger-like projections called epidermal ridges. Epidermal cells receive their nutrients and oxygen from blood vessels in the dermis due to the fact that the epidermis does not have its own blood vessels. The epidermal ridges in DEJ increase the surface area of the epidermis that is exposed to the dermis so that absorption of necessary nutrients/oxygen is more effective, and the two layers of skin can bond more tightly and resist mechanical stress. DEJ narrows with aging, so the skin is more fragile and more prone to shear. This process also decreases the amount of nutrients/oxygen available to the epidermis by decreasing the surface area of the epidermis in contact with the dermis, thus interfering with the skin's normal repair process. As a result, the skin shows signs of aging such as fragility, fine lines and wrinkles, sagging, dullness, discoloration and uneven tone, rough texture and the like. The main structural component of the dermis is also collagen. Bundles of collagen molecules pack together throughout the dermis, accounting for three-quarters of the skin's dry weight. Pro-collagen is the collagen precursor molecule, synthesized in fibroblasts, osteoblasts, etc., and cleaved to form collagen extracellularly. Collagen has great resistance to traction, and together with soft keratin, it is responsible for the skin's elasticity and strength. As aging occurs, collagen production is reduced, while degradation is accelerated due to an overproduction of collagenase, that is, a protease that breaks down collagen. Collagen deficiency can lead to a reduction in skin resistance and elasticity, which, in turn, can lead to wrinkles, sagging and fragility of aging skin. For more detailed fundamentals about collagen, see Lodish, et al. Molecular Cell Biology, WH FREEMAN, New York, NY 4th edition, 2000. Thus, it is anticipated that retention or stimulation of collagen and/or procollagen production and/or reduction in collagenase production would provide a healthier and stronger skin, thus reducing wrinkles, sagging and fragile aging skin.
[0110] Suitable barrier enhancing agents include phytol, and ceramides such as ceramide-2, glycerides, cholesterol and its esters, alpha and omega-hydroxy fatty acids and esters thereof, etc.; and others listed elsewhere in this application.
[0111] Such suitable anti-inflammatory agents include thiodipropionic acid; and others listed elsewhere in this application.
[0112] Suitable anti-cellulite agents (in one embodiment, intracellular triglyceride inhibitors) include Coleus forskohlii; CPT-1 modulators; star fruit extract; caffeine; and others listed elsewhere in this application. Cellulite is the lumpy, lumpy type of subcutaneous fat that tends to accumulate on the buttocks, thighs, and limbs of many women. It is considered unpleasant in appearance because it gives the tissues underlying the skin an "orange peel" or "cottage cheese" appearance. Compression of the skin, when sitting or crossing the legs, produces a "mattress appearance" with bulges and holes in the grease layer. Fat nodules may appear to be trapped within hardened connective tissue. Histology of skin affected with cellulite indicates that cellulite results from a combination of enlarged fatty tissue and weak dermal structure and connective tissue septa. Excess fat accumulation increases the volume of adipocytes, which grow in a weakened dermis to create the characteristic irregularities in the appearance of the epidermal surface. Several factors can cause cellulitis including, for example, hereditary, intestinal, circulatory, lymphatic, hormonal and lifestyle factors. Diet to decrease fat intake, exercise to increase fat metabolism and prevent cellulite from developing, and massage and hydrotherapy to stimulate lymphatic drainage can help reduce the appearance of cellulite. However, these means of combating cellulite or subcutaneous fat are limited and the need for additional approaches remains. The bulge of enlarged fatty tissue in the dermis is one of the main factors that contribute to the appearance of cellulite. One of the approaches to improving cellulite is to stimulate fat breakdown and reduce the amount of fat and/or lipids in adipocytes or fat cells.
[0113] Suitable hydroxylic acids and derivatives thereof include sodium glycolate; oxa diacids; alpha-hydroxy acid; and others listed elsewhere in this application.
[0114] Suitable retinoids and derivatives thereof include retinol; and others listed elsewhere in this application.
[0115]Suitable antioxidants include thiodipropionic acid; and others listed elsewhere in this application.
[0116] Suitable vitamins include niacinamide; and others listed elsewhere in this application.
[0117] Suitable terpene alcohols include phytol; and others listed elsewhere in this application.
[0118] Suitable peptides include K-ava-K; KTFK; n-acetyl tyrosinamide; and others listed elsewhere in this application.
[0119] Suitable PPAR modulators include phytol and others listed elsewhere in this application.
[0120] Suitable botanicals include Portulaca oleracea; Tiliacora triandara; Berchemia lineata; and others listed elsewhere in this application.
[0121] Suitable exfoliating agents include, for example, alpha-hydroxy acids, beta-hydroxy acids, oxa-acids, oxadiacids, and their derivatives such as esters, anhydrides and salts thereof. Suitable hydroxy acids include, for example, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, 2-hydroxyalkanoic acid, mandelic acid, salicylic acid and derivatives thereof. An exemplary exfoliating agent is glycolic acid. When present, the exfoliating agent can comprise from about 0.001% to about 20% by weight of the composition.
[0122] Examples of antioxidants that can be used in the present compositions include compounds that have phenolic hydroxy functions, such as ascorbic acid and its derivatives/esters; beta-carotene; catechins; curcumin; ferulic acid derivatives (eg ethyl ferulate, sodium ferulate); gallic acid derivatives (eg propyl gallate); lycopene; reductic acid; rosmarinic acid; tannic acid; tetrahydrocurcumin; tocopherol and its derivatives, including tocopheryl acetate; uric acid; or any mixtures thereof. Other suitable antioxidants are those which have one or more thiol (-SH) functions, in reduced or unreduced form, such as glutathione, lipoic acid, thioglycolic acid and other sulfhydryl compounds. The antioxidant can be inorganic, such as bisulfites, metabisulfites, sulfites or other inorganic salts and acids that contain sulfur. Antioxidants can comprise, individually or collectively, from about 0.001% to about 10% (by weight) or from about 0.01% to about 5% (by weight) of the total weight of the composition.
[0123]Other additives include: vitamins such as tocopherol and ascorbic acid; vitamin derivatives such as ascorbyl monopalmitate, tocopheryl acetate, and vitamin E palmitate; thickeners such as hydroxyalkyl cellulose, carboxymethylcellulose, carbomers, and vegetable gums such as xanthan gum; gelling agents such as ester-terminated polyester amides; structuring agents; metal chelating agents such as EDTA or salts thereof; pigments; colorants; and pH adjusters (citric acid, ethanolamine, sodium hydroxide, etc.). The composition may optionally comprise other components known to those of skill in the art including, but not limited to, film formers, moisturizers, minerals, rheology and/or viscosity modifiers, anti-acne agents, insect repellants, water freshener compounds. skin, skin protectors, lubricants, fragrances, preservatives, stabilizers and mixtures thereof. In addition to the aforementioned, the cosmetic compositions of the invention may contain any other compound for the treatment of skin disorders.
[0124] In addition, the compositions contemplated by this disclosure may include one or more cosmetically acceptable and compatible adjuvants commonly used and known to the skilled practitioner, such as colorants, pearls, chromates, micas, pigments, dyes, fragrances, emollients, humectants , preservatives, vitamins, chelators, thickeners, anesthetics, antiallergens, antifungals, antimicrobials, other anti-inflammatory agents, antioxidants, antiseptics, depigmentation agents, film formers, insect repellants, pharmaceutical agents, photo-stabilizing agents, protectants sunscreens, stabilizers, surfactants, thickeners, viscosity modifiers and botanicals. The topical compositions of the present disclosure can also include a skin penetration enhancer, a surface softener, a skin toner, an optical diffuser, an exfoliation enhancer and an antioxidant. Details regarding these and other suitable cosmetic ingredients can be found in the "Inter-national Cosmetic Ingredient Dictionary and Handbook", 10th edition (2004), published by the Cosmetic, Toiletry, and Fragrance Association (CTFA), at pages 2177 to 2299, which is incorporated herein by reference in its entirety. The amounts of these various substances are those that are conventionally used in the cosmetic or pharmaceutical fields, for example, may constitute from about 0.01% to about 20% of the total weight of the composition.
[0125]A sunscreen may be included to protect the skin from damage from ultraviolet rays. In an illustrative embodiment of the present disclosure, the sunscreen provides both UVA and UVB protection with the use of a single sunscreen or a combination of sunscreens. Among the sunscreens that can be used in the present compositions are avobenzone, cinnamic acid derivatives (such as octylmethoxy cinnamate), octyl salicylate, oxybenzone, octocrilene, titanium dioxide, zinc oxide or any mixtures thereof. The sunscreen may be present from about 1% by weight to about 30% by weight of the total weight of the composition.
[0126] In one embodiment, topical compositions will have a pH that is in the range from 1 to 13, with a pH in the range from 2 to 12 being typical. In some embodiments, the composition will have a pH in the range from 3.5 to 7 or from 7 to 10.5. In some embodiments, the pH will range from 3 to 4, 4 to 5, 5 to 6, 6 to 7, 7 to 8, 8 to 9, 9 to 10, 10 to 11 or 11 to 12. Suitable pH's such as sodium hydroxide, citric acid and triethanolamine can be added to bring the pH within the desired range.
[0127] It will be understood that the optional inactive active ingredient (or ingredients) mentioned above may be included in one or all of the compositions according to the inventions (for example, in both the first and second compositions).
[0128] Another embodiment of the present disclosure is directed to the delivery of the compositions described through the use of targeted delivery systems, for example, liposomes, injection, microspheres, (see, for example, patent no. US 5,770,222 to Unger et al.) and the like, so that the active components and/or constituents can more readily reach and affect the subcutaneous layer of the area of application, eg, face or neck, or other area of skin.
[0129] Compositions can be formulated in a variety of product forms, such as, for example, a lotion, cream, serum, spray, aerosol, cake, ointment, essence, gel, paste, plaster, pencil, handkerchief, mask, stick, foam, elixir, concentrate and the like, particularly for topical administration. Compositions are typically formulated as a lotion, cream, ointment or gel. The first and second compositions can also take different shapes from each other.
[0130] In certain embodiments of the invention, the compositions are applied topically to improve the appearance and/or health of human skin. The improvement in the appearance and/or health of human skin may be an improvement of any attribute or characteristic of the skin, including, without limitation: (a) treating, reducing and/or preventing fine lines or wrinkles; (b) skin pore size reduction; (c) improvement in skin thickness, plump appearance and/or tightness; (d) improvement in smoothness, elasticity and/or smoothness of the skin; (e) improvement in skin tone, radiance and/or clarity; (f) improvement in pro-collagen and/or collagen production; (g) improvement in elastin maintenance and remodeling; (h) improvement in skin texture and/or promotion of retexturization; (i) improvement in skin barrier function and/or repair; (j) improvement in the appearance of skin contours; (k) restoration of skin shine and/or luminosity; (l) replacement of essential nutrients and/or skin constituents; (m) improvement in skin appearance diminished by aging and/or menopause; (n) improvement in skin hydration; (o) increase in skin elasticity and/or resilience; (p) treatment, reduction and/or prevention of sagging skin; (q) improvement in skin firmness; and (r) reduction of pigmented spots and/or mottled skin; and (s) improvement of the skin's optical properties through light reflection or diffraction.
[0131] In some embodiments, the compositions are intended to treat wrinkles and/or fine lines on the skin, including forehead wrinkles, "crow's feet" and wrinkles at the corners of the eyes or mouth. In some embodiments, compositions are applied directly to a wrinkle and/or fine line. Treatment can reduce the severity (eg depth) of wrinkles and fine lines and/or can reduce the number of wrinkles and/or fine lines in a particular area of skin. In some embodiments, the compositions are intended to treat sagging skin that can result from a loss of dermal elasticity. In this modality, the compositions can be applied to the skin of the cheeks, jowls, etc.
[0132] It is also contemplated that the methods of the invention will be useful for the treatment of thin skin by topically applying the composition to the thin skin of an individual in need of such treatment. "Thin skin" is intended to include skin that is thinned due to chronological aging, menopause or photon, and skin that is prematurely thinning. In some modalities, the treatment is for thin skin in men, while other modalities treat thin skin in women, pre-menopausal or post-menopausal, as the skin is believed to thin differently with age at men and women, and, in particular, in women at different stages of life.
[0133] The methods of the invention can be employed prophylactically to prevent aging, including in individuals who have not manifested signs of skin aging, most commonly in individuals over 25 years of age. The methods can also reverse or treat signs of aging once manifested, as is common in individuals over 25 years of age, or slow the progression of dermatological aging in such individuals.
[0134] In certain embodiments, the cosmetic compositions described herein can be used to treat and/or prevent hyperpigmentation of the skin and/or hair, for example, to lighten the skin or hair. In some embodiments, the compositions are applied topically to the skin or hair, for example, to a hyperpigmented area of skin or hair. Hyperpigmentation includes any coloration of an individual's hair or skin that is darker than the individual desires and that is caused by melanocytes. Such unwanted pigmentation can also be called discoloration. Hyperpigmented areas of the skin include areas of mild or mottled hyperpigmentation. Areas of slight hyperpigmentation may be distinct uniform areas of darker color and may appear as brown spots or freckles on the skin, including marks commonly called pigmented spots or "age spots". Areas of mottled hyperpigmentation of the skin can be dark patches that are larger and more irregular in size and shape than the area of mild pigmentation. Areas of hyperpigmentation also include areas of tanned skin, for example, tanned skin due to UV exposure. Hyperpigmented hair includes any hair shade that is darker than desired.
[0135]The treatment of hyperpigmentation or hyperpigmented skin/hair refers to the eradication, reduction, mitigation, or reversal of one or more of the unwanted features associated with hyperpigmentation, such as producing a noticeable lightening of the skin or hair in the affected area. Lightening of hyperpigmented areas of the skin may be desirable, in one way, to reduce age spots; lightening a tan; smoothing or optimizing skin tones, for example, in areas of mottled hyperpigmentation; in the treatment of melasma and chloasma spots, freckles, scars after burns and post-injury hyperpigmentation. The prevention of hyperpigmentation or hyperpigmented skin refers to providing the skin, not yet affected by hyperpigmentation, with a benefit that serves to prevent, delay, prevent or minimize one or more unwanted characteristics associated with hyperpigmentation of the skin, such as reduced skin darkness or size of hyperpigmented areas that eventually develop.
[0136] In one embodiment, the compositions of the invention are applied to human skin to reduce sebum production or improve the appearance of skin affected by cellulite and/or reduce unwanted lipogenesis or increase lipolysis. In this embodiment, terpene alcohols and/or retinoids can be formulated into cosmetically acceptable vehicles (as described herein) and can include one or more additional agents such as anti-acne ingredients (e.g., salicylic acid, benzoyl peroxide, and others peroxides, sulfur, retinoids, etc.) in the case of a facial makeup, or, in the case of a cellulite treatment, the formulation may comprise any ingredients suitable for the treatment of cellulite, including, without limitation, Coleus forskohlii, oil from perilla and other unsaturated fatty oils and omega-3 fatty acids such as alpha-linolenic acid; Conjugated linoleic acid (CLA); caffeine; theophylline; xanthines; retinoids (for example, retinol); epigalosequine gallate; and the like. A cellulite treatment composition according to the invention may comprise effective amounts of a lipolysis stimulator, lipogenesis inhibitor or an adipogenesis inhibitor. Cellulite treatment may comprise a PPAR ligand, which may be an inhibitor of the up-regulation of any of the PPAR isoforms, such as PPAR-α and/or PPAR-Y. Cellulite treatment can comprise CPT-1 inhibitor, for example, and star fruit extract. A cellulite treatment in accordance with the invention will typically be applied topically to skin suffering from cellulite, including the skin of the buttocks and thighs, for a period of time sufficient to improve the appearance thereof, including, for example, daily treatment during hair. at least four weeks, at least eight weeks, at least twelve weeks or longer. In one modality, the compositions are applied topically to treat acne.
[0137] In one embodiment, the compositions are intended for use as a non-therapeutic treatment. In another embodiment, compositions are articles intended to be rubbed, poured, dusted or sprinkled on, introduced into or otherwise applied to the human body for cleaning, beautifying, promoting attractiveness or altering appearance, in accordance with the US FD&C Act, §201(i).
[0138] In another embodiment, a kit and/or a treatment method for periodic or rotating skin care is contemplated. The kit may comprise: (i) one of a plurality of topical compositions comprising a physiologically acceptable carrier; (ii) a second of a plurality of topical compositions comprising a physiologically acceptable carrier, said first topical composition being physically separate from said second topical composition, and (iii) optionally, written instructions for topically applying said first and second topical compositions in alternating mode, in any order, so that the first composition is applied at least once a day for a first time period from 1 to 31 days and said second composition is applied at least once per day for a second period of time from 1 to 31 days.
[0139] In one embodiment, the plurality of compositions are each contained in a separate container as a single ingredient, in which multiple single-formula containers (eg, jars and dispensers) are sold and/or packaged together .
[0140] In another modality, the plurality of compositions exists as different physical layers within the same container (for example, separated by density and/or layer miscibility), which can be packaged in pots, dispensers and/or others types of container.
[0141] In another modality, the plurality of compositions is contained in different sachets that can themselves be packaged and/or sold together, and that can be arranged linearly; in an array; and/or radially.
[0142] In another modality, the plurality of compositions is contained in different blister packs that can themselves be packed and sold together, and that can be arranged linearly; in an array; and/or radially.
[0143] In another embodiment, the plurality of compositions is contained in different reservoirs within the same package.
[0144] In another modality, the plurality of reservoirs each comprises a single dose of said first and second topical compositions, respectively.
[0145] In another modality, the plurality of reservoirs is not separable from one another.
[0146] In another embodiment, the plurality of reservoirs is marked with a plurality of different identifiers (for example, color, symbol, light, display, QR code, etc.), respectively.
[0147] In another modality, an identifier (eg color, symbol, light, display, QR code, etc.) is used to indicate to the user to switch the use of a first composition to a second composition and/or which composition to use at a given treatment opportunity. In another modality, the package contains an indicator light that indicates whether the user must apply the first composition or the second composition. In another embodiment, the first and/or second containers contain an electronic display that indicates whether the user should apply the first composition or the second composition.
[0148] In another modality, the written instructions indicate to the user which modality of treatment to use on a particular day by referring to the plurality of identifiers.
[0149]In another modality, the order of treatment modalities to use is stochastic or randomly generated.
[0150] In another embodiment, the method or kit additionally includes a calendar, the calendar identifying a first time period ranging from 1 to 31 days, said first time period being marked with said first identifier, and a second time period ranging from 1 to 31 days, said second time period being marked with said second identifier. In another embodiment, the method or kit additionally includes written instructions (eg, a QR code) for accessing a calendar on the Internet, wherein said calendar instructs the user to apply the first or second composition depending on the day. In one modality, the calendar will have, each day, an indicator or symbol that uniquely identifies one of the compositions, which can, for example, be packaged in containers or reservoirs also identified by the same indicators or symbols.
[0151] In another embodiment, the method or kit additionally includes written instructions for accessing data on the Internet (eg a QR code), in which the data (eg in the form of an algorithm or application or under the form of a text message or other data communication) provides the user with instruction as to which modality of treatment to apply; and where data can be accessible through a smart phone application, website, etc.
[0152] In other embodiments, a system is provided comprising a skin care product and a server and optionally a computer away from the server. The skin care product can be as described herein and can have, for example, separate in different reservoirs within the same package or container, two different skin care compositions that can be independently dispensed from said packaging or container; and an indicator for distinguishing between said skin treatment compositions. The server is typically configured to receive, on a computer network, from a user of said skin care product, a date on which a skin treatment regimen is initiated, and configured to send, over a network of computers, to said user a plurality of notifications on a plurality of different days that instruct the user as to which of said first and second skin treatment compositions to apply topically to said skin. The skin care product may further comprise an identifier (e.g. alphanumeric code, barcode, QR code, etc.) which is capable of identifying said skin treatment compositions, and the server may be configured to receive said identifier from the user in addition to a start date. Based on the identifier, the server can use information regarding the first and second compositions in the particular product and said start date to calculate the treatment regimen for said first and second compositions. For example, the server can be instructed to use a private value for the first time period and a private value for the second time period based on the identifier. The server can be configured to send, over a computer network, to said user a plurality of notifications on a plurality of different days that instruct the user as to which of said first and second skin treatment compositions to apply topically to the said skin, based on user input of a start date and a predetermined duration of the first and second period of time. The system may further comprise a remote server computer (e.g. mobile phone, telephone, smart phone, tablet computer, body worn device, watch, pager, computer, laptop computer, etc.), under the control of the user, to send the start date to said server and to receive the plurality of notifications.
[0153]Now referring to Figure 6, a flowchart illustrates the process and system where a user, for example, through a computer (eg smart phone, laptop computer, desktop computer, etc.), sends a start date and said server receives said start date in step 100. Sending and receiving can take place over a network, such as the Internet, a wireless network, land lines, satellite, etc. Based on the start date, the server determines a schedule for the first treatment modality using the first predetermined time period (typically from 1 to 31 days, 2 to 15 days, or 7 days) at step 200. This may entail adding the first time period to the start date. The user would apply a first composition of the product during that first period of time. The server may notify (eg, by text message, email, social media post, phone, etc.) the user one or more times (eg, daily) during the first treatment moment to apply the first composition in that day. Alternatively, the server can notify the user only when it is time to change the treatment to the second composition, for example, before the end or end of the first treatment period in step 300. The server can use the start date to determine an end date for the first treatment regimen, based on predetermined or user-supplied input of a first treatment time period. For example, the first treatment period can be seven days, which can be a predetermined instruction on said server or can be entered or selected by the user. Before the end date of the first treatment modality, the server can calculate the start and end date of a second treatment modality, again based on the predetermined input or based on the input supplied by the user for the desired duration of the second treatment regimen at step 400. This may entail adding the first time period and second time period to the start date, or adding the second time period to the value determined in step 200 (ie, the end of the first time schedule of treatment). The server may notify the user before the end or at the end of the second treatment regimen to start the first treatment regimen on a certain date in step 500. The server may repeat steps 200 to 500 for any number of iterations, typically more than four. The number of iterations based on predetermined input or based on user-supplied input. On the second or any larger iteration, the server can repeat steps 200 to 500 based on the start date, the length of the first and second time periods, and the iteration number. Alternatively, the server may send notifications of any first or second treatment modality during any prior first or second period of time.
[0154] In another modality, the user can scan or image his treated inte-gument, for example, with the use of a smart phone camera, and send the scan or image to the server. The server can be configured to generate personalized instructions on further treatment from application or Internet data, and send those instructions to the user's computer over the network.
[0155] In another embodiment, the first and second compositions are contained in separate reservoirs within a single container, wherein the container has a first pump in fluid communication with the reservoir that contains the first composition for dispensing of said first composition and a second pump in fluid communication with the reservoir containing the second composition for dispensing said second composition, each pump optionally being disposed on the opposite side of said container, and each pump optionally being covered by a removable cap so that the user removes the cap from one end while retaining the cap covering the other end.
[0156] Referring now to Figures 7 and 8, there is illustrated a skin care product 10 comprising a container 12 comprising a first reservoir 14 containing a first skin treatment composition 60 and a second reservoir 16 containing a second skin treatment composition 62 different from said first skin treatment composition, a first pump 26 in fluid communication with first reservoir 14 for dispensing said first skin treatment composition, and a second pump 22 in fluid communication with second reservoir 16 for dispensing said second skin treatment composition. The first and second bombs can be the same or different. Any suitable pump used in cosmetic or personal care techniques is contemplated as suitable. Figure 7 shows a view illustrating the internal contents of reservoirs 14 and 16 distinguished as a first composition 60 and a second composition 62. Referring to Figures 9 to 11, cross-sectional views of the product 10 are shown. pumping mechanisms 20 and 22, in this modality, comprise tubes 21 and 23 for transporting liquid compositions from each reservoir and dispensing them through orifices 26 and 28. Springs 25 and 27 actuate the pump according to well-known designs. A barrier 40 separates the first reservoir from the second reservoir. Barrier 40 may be integral with container 12 so that the two reservoirs cannot be separated from one another. Removable caps 30 and 32 are affixed to each respective end of the container and cover pumps 20 and 22 when seated on the container. With reference to Figures 12A and 12B, an embodiment of the skin care product is shown, wherein the exterior of the container or its label affixed thereto contains alphanumeric indicators "1" and "2" that distinguish the first and the second reservoirs. The product according to this embodiment may include visible identifiers 50 indicating each day of the week, for example, printed on a label affixed to the container. In Figure 12B, the product has a user-placed circular sticker 55 on the appropriate day of the week on which the treatment regimen began (eg, Monday or "S"), to serve as a reminder to switch between first and second. -first and second treatment compositions each week on that particular day.
[0157] In another embodiment, a plurality of compositions may be contained in a plurality of separate reservoirs within a single container, wherein the container contains a pump in fluid communication with the reservoir containing the first composition for dispensing said first composition and a pump in fluid communication with the reservoir containing the second composition for dispensing said second composition, wherein the pumps form a multi-sided toggle mechanism (e.g., toggle pump) so that the actuation of the alternation mechanism to deliver a first composition will prepare the actuation mechanism to optionally deliver a second composition while preventing the actuation of the alternation mechanism to deliver the first or any other composition until the prepared alternation mechanism is actuated to deliver the second composition.
[0158] In another embodiment, a plurality of optionally refillable single-use capsules can be used, each capsule comprising a reservoir containing a unit dose of a topical composition and a dispenser for dispensing said composition, wherein at least one of said capsules contains a first topical composition and at least one of said capsules contains a second topical composition; wherein the plurality of capsules is releasably attached directly or indirectly to one another, and may be individually separated from the plurality before dispensing the topical composition contained therein.
[0159] In another embodiment, the capsules containing said first topical composition are visually distinct from the capsules containing said second topical composition.
[0160] In another embodiment, the dispenser comprises a breakable plug configured to expose a hole in said capsule when ruptured.
[0161] In another embodiment, the first and second compositions are contained in separate reservoirs within a single container, wherein at least one of the compositions is in the form of a transparent gel, and at least a portion of the wall of said The container is transparent or translucent, such that the first and/or second composition is visible through said portion of said container wall, and wherein the container has an indicator to illuminate said transparent gel composition to indicate when that composition must be applied.
[0162] In another embodiment, a plurality of compositions is contained in separate reservoirs within a single container, and wherein a rotary dispenser is configured to dispense the first composition or second composition through a common opening depending on the degree rotation of the swivel dispenser.
[0163] In another embodiment, a kit or method is used which comprises: (i) one or more compositions comprising a physiologically acceptable vehicle and an effective amount of a skin care active ingredient; (ii) at least one device for imparting mechanical or electromagnetic energy to the skin, and (iii) written instructions for topically applying said first topical compositions for a first period of time and using said device on the same area of skin during a second period of time, in any order, and repeat one or more times. The device can give light; radiate; deliver a radio frequency; deliver heat; deliver an electrical current; deliver cold; to polish; exfoliate; check suction; oxygenate; or otherwise apply a phenomenon to the skin. EXAMPLES
[0164]The following example illustrates a specific aspect of this description. The example should not be interpreted as limiting, as the example simply provides a specific and practical understanding of the modalities and their various aspects. In each of the following examples using an extract of the Tiliacora triandra plant, the extract was prepared from hydropically grown Tiliacora triandra and extracted with an 80/20 (v/v) ethanol/water solvent. EXAMPLE 1
[0165] Human dermal fibroblast cells were cultured in a 6-well plate in DMEM medium (available from Corning, NY) supplemented with 10% fetal bovine serum (FBS) and L-glutamine (1.5x105 cells/plate ) overnight. After reaching about 75% confluence, cells were transferred to DMEM medium without FBS and incubated for 4 to 6 hours. Then, cells were treated with 0.0001% phytol or 1 μM retinol. Treatment with phytol alone or retinol alone was carried out in DMEM medium without FBS for 16 days. For sequential treatments, cells were treated with 0.0001% phytol for 6 days followed by 1 μM retinol for 10 days, or with 1 μM retinol for 6 days, followed by 0.0001% phytol for 10 days. On alternate days, media were collected and cells were again treated with phytol or retinol in the same manner. After treatment, the amount of collagen secreted into the culture medium was determined using the HTRF human procollagen I kit (available from CISBIO, Inc).
[0166]The results are shown in Figures 1 to 2. Figure 1 represents levels of procollagen in cells treated with phytol or retinol alone. Procollagen production declines for both phytol and retinol treated cells after day 13 despite continued treatment. Figure 2 shows collagen production for untreated ("control") cells, cells treated with phytol, cells treated with retinol, as well as cells treated first with retinol followed by phytol, and cells treated first with phytol followed by of retinol. It is evident that cells treated sequentially show increased collagen production compared to cells treated with a single active principle. EXAMPLE 2
[0167]The clinical efficacy of a rotating regimen has been demonstrated as set out below.
[0168] Subjects (age range: 24 to 59) who have mild to moderate expression lines and wrinkles were recruited into the study. Subjects were allocated to two groups: Cell 1 received a treatment regimen comprising topical application of an α-hydroxy acid (AHA) formulation once daily for one week, followed by topical application of a retinol formulation once daily to the same area of skin on the face for one week. These treatments were continued in a rotational fashion for a total of 12 weeks. Subjects in Cell 2 received only topical retinol treatment once daily for the entire 12 weeks. All subjects underwent a two-week preconditioning during which they did not receive AHA or retinol therapy. All subjects applied a sunscreen on their face daily during the conditioning period and throughout the 12-week test.
[0169] The a-hydroxy acid (AHA) formulations, eg, glycolic acid, and Retinol that were used in this study are provided below in Table 1.Table 1.

[0170]The area of application was assessed and scored by a dermatologist at baseline and after 4, 8, and 12 weeks.
[0171]The results are summarized below in Table 2. Table 2.

*Statistically significant (p < 0.05) improvement over retinol treatment (Cell 2).
[0172]As shown in Table 2, improvements from baseline were seen within four weeks of the start of the study, with marked improvements in skin tone, clarity, and reduction in mild pigmentation. At twelve weeks, a statistically significant reduction in the appearance of expression lines was found for the rotating treatment group (Cell 2) compared to the retinol treatment group (Cell 1). This result was surprising due to the fact that the rotating group (Cell 1) received half the total dose of retinol that the retinol group received, and AHA therapy is not generally considered capable of achieving the magnitude of reduction in wrinkles/expression lines such as retinol. EXAMPLES
3 to 10
[0173]Evaluation of hyaluronic acid (HA) in human dermal fibroblasts
[0174] A series of experiments was conducted to evaluate the effects of active ingredient treatment regimens on the production of hyaluronic acid (HA) in human dermal fibroblast (HDF) cells. The following five treatment regimens were evaluated: (1) active ingredient A alone; (2) active ingredient B alone; (3) the combination of active ingredients A + B; (4) active ingredient A alone, followed by active ingredient B alone ("A/B"); and (5) active ingredient B alone, followed by active ingredient A alone ("B/A"). For treatment regimens (1), (2) and (3), active ingredients were administered to the cells for 10 consecutive days. For treatment regimens (4) and (5) (sequential regimens), cells were treated with active ingredient A or active ingredient B for 5 days, followed by active ingredient B or active ingredient A for 5 days, respectively.
[0175]Human dermal fibroblast cells were cultured in a 96-well plate in DMEM medium (available from CORNING, NY) supplemented with 10% FBS and L-glutamine. After reaching about 75% confluency, cells were transferred to DMEM medium without FBS and incubated for 4 to 6 hours. Different wells were assigned to one of the treatment regimens (1) to (5) as described above, with six wells allocated to each treatment regimen (ie, n=6). All active ingredients were prepared as emulsions and applied directly to HDF cells. The specific active ingredients used in each of the five treatment regimens are provided below in Table 3. After treatment, cells were collected and the amount of hyaluronic acid (HA) secreted from the cells was measured using a commercially available HA assay (available from CORGENIX Inc., CO).

[0176]The results are summarized below in Table 4 and plotted in Figures 13 to 17 as a percentage change from the control (ie, cells treated with the same emulsion but in the absence of active ingredients).


[0177]As shown in Table 4 and Figures 13 to 17, the sequential treatment of certain active ingredients is effective in stimulating the production of HA. Sequential treatment resulted in a more than additive improvement in Examples 3 to 6 and 10. Examples 3 to 5 and 10 each showed statistically significant higher HA production compared to when those active ingredients are used alone or simultaneously. For example, Example 3 (see Figure 11) demonstrates that sequential treatment of niacinamide followed by Tiliacora triandra extract results in higher levels of HA produced than with treatment with Tiliacora triandra alone, niacinamide alone, or simultaneous application of Tiliacora triandra and niacinamide. EXAMPLE 11
[0178]HA measurement in full thickness 3D skin models for rotary treatment regimens.
[0179] A series of experiments was conducted to evaluate the effects of glycolic acid and Tiliacora triandra treatment regimens on hyaluronic acid (HA) production in full thickness 3D skin cultures. Five different treatment regimens were evaluated: (1) 4% glycolic acid alone; (2) Tiliacora triandra 0.2%, alone; (3) the combination of 4% glycolic acid + 0.2% Tiliacora triandra; (4) 4% glycolic acid alone, followed by 0.2% Tiliacora triandra alone; and (5) Tiliacora triandra 0.2% alone, followed by 4% glycolic acid alone. Glycolic acid was administered topically to the 3D tissue and Tiliacora triandra was administered through the growth medium. For treatment regimens (1), (2) and (3), the active ingredient or ingredients were applied to the cells for 4 consecutive days. For treatment regimens (4) and (5) (sequential regimens), cells were treated with glycolic acid or Tiliacora triandra for 2 days, followed by Tiliacora triandra or glycolic acid for 2 days, respectively.
[0180]EFT400FT 3D human skin tissues (MatTek, MA) were cultured following the manufacturer's instructions. Each treatment regimen was applied to twelve 3D skin samples. Different 3D skin samples were assigned to one of the treatment regimens (1) to (5) as described above, with twelve skin tissue models allocated to each treatment regimen (ie, n=12). After treatment, cells were collected and the amount of hyaluronic acid secreted from the cells was measured using a commercially available HA assay (available from CORGENIX Inc., CO).

[0181]The results are shown in Table 5 and plotted in Figure 18 as a percentage change from the control (ie, models treated with the same emulsion but in the absence of active ingredients). Sequential treatment with glycolic acid followed by Tiliacora triandra extract is effective in stimulating HA production. Example 11 (see Figure 16) demonstrates that a sequential treatment of glycolic acid followed by Tiliacora triandra results in statistically significant higher produced HA levels than with treatment with either active ingredient alone. EXAMPLES
12 to 13
[0182]Evaluation of type I procollagen in human dermal fibroblasts
[0183] A series of experiments was conducted to evaluate the effects of the active ingredient treatment regimens shown in Table 6 on the production of type I procollagen in human dermal fibroblast (HDF) cells. Five different treatment regimens were evaluated: (1) active ingredient A alone; (2) active ingredient B alone; (3) the combination of active ingredients A + B; (4) active ingredient A alone, followed by active ingredient B alone; and (5) active ingredient B alone, followed by active ingredient A alone. For treatment regimens (1), (2) and (3), active ingredients were applied to cells for 10 consecutive days. For treatment regimens (4) and (5) (sequential regimens), cells were treated with active ingredient A or B for 5 days, followed by treatment with the other active ingredient B or A for 5 days, respectively.
[0184]Human dermal fibroblast cells were cultured in a 96-well plate in DMEM medium (available from CORNING, NY) supplemented with 10% FBS and L-glutamine. After reaching about 75% confluency, cells were transferred to DMEM medium without FBS and incubated for 4 to 6 hours. Different wells were assigned to one of the treatment regimens (1) to (5) as described above, with six wells allocated to each treatment regimen. All active ingredients were prepared as emulsions and applied directly to HDF cells. The specific active ingredients used in each of the five treatment regimens are provided below in Table 6. After treatment, measurements on the amount of procollagen produced from the cells were performed using a linked immunosorbent assay kit to commercially available type I procollagen enzyme (ELISA) (available from TAKARA Inc., KR).


[0185]The results are shown in Table 7 and plotted in Figure 19 to 20 as a percentage change from the control (ie, cells treated with the same emulsion but in the absence of active ingredients).

[0186] As shown in Table 7, sequential treatment of Coleus forskohlii extract followed by retinol in human dermal fibroblast cells results in statistically significant improvement in type I procollagen production compared to treatment using retinol alone , Coleus forskohlii alone or simultaneous application of retinol and Coleus forskohlii'. Similarly, it is evident that sequential treatments of phytol/retinol (A/B) and retinol/phytol (B/A) in HDF cells produce statistically significant more type I procollagen than treatments of cells with any principle active. Sequential retinol/phytol treatment resulted in a more than additive improvement in Example 13. EXAMPLES
14 to 16
[0187]Melanin in 3D skin models
[0188]A series of experiments were conducted to evaluate the effects of the active ingredient treatment regimens shown in Table 8 on melanin production in 3D models. Four different treatment regimens were evaluated: (1) active ingredient A alone; (2) active ingredient B alone; (3) the combination of active ingredients A + B; and (4) active ingredient A alone, followed by active ingredient B alone, as detailed in Table 8. For treatment regimens (1), (2) and (3), the active ingredients were applied to cells for 14 consecutive days. For treatment regimen (4) (sequential regimen), cells were treated with active ingredient A for 7 days, followed by treatment with the other active ingredient B for 7 days.

[0189] 3D MelanoDerm MEL-B human skin tissues (available from MatTek, MA) were cultured following the manufacturer's instructions. Different skin tissue models were assigned to one of the treatment regimens (1) to (4) as described above, with six models allocated to each treatment regimen (ie, n=6). All active ingredients were prepared as emulsions and applied directly to skin models. The specific active ingredients used in each of the four treatment regimens are provided in Table 8. After treatment, skin tissue models were collected and the amount of melanin produced from the cells was measured using a SOLVABLE melanin. The treated skin tissues were prepared using a saline solution of phosphate buffer and sodium bicarbonate. Each skin tissue is added to 500 µl of 0.5 M SOLVABLE solubilizer (available from Packard BioScience) and incubated at 95° overnight. The absorbance of each skin tissue sample is measured at 490 nm and the absorbance is compared to a standard curve to indicate the amount of melanin produced and pigmentation in each skin tissue model.

[0190] Results for treatments that measure the content of melanin produced are shown in Table 9 as a percentage change from the control (ie, untreated samples or samples treated with the same emulsion but in the absence of active ingredients ). EXAMPLE 17
[0191]Evaluation of hyaluronic in human dermal fibroblasts in response to pulsed treatment regimens
[0192]A series of experiments were conducted to evaluate the effects of different treatment regimens of active ingredients shown in Table 9 on the production of hyaluronic acid (HA) in human dermal fibroblast (HDF) cells. Two different treatment regimens were evaluated: (1) active ingredient A applied to cells for 12 consecutive days; and (2) active ingredient applied to the cells for 2 consecutive days followed by application of media that does not contain active ingredient for two consecutive days repeatedly, until the treatment has been applied for 12 consecutive days.
[0193] Human dermal fibroblast cells were cultured in a 96-well plate in DMEM medium (available from CORNING, NY) supplemented with 10% FBS and L-glutamine. After reaching about 75% confluency, cells were transferred to DMEM medium without FBS and incubated for 4 to 6 hours. Different wells were assigned to one of the treatment regimens (1) to (2) as described above, with six wells allocated to each treatment regimen. All active ingredients were prepared as emulsions and applied directly to HDF cells. The specific active ingredients used in each of the two treatment regimens are given below in Table 10. After treatment, cells were collected and the amount of hyaluronic acid (HA) secreted from the cells was measured with use of a commercially available HA assay (available from CORGENIX Inc., CO).

[0194]Results are summarized in Table 10 as a percent change from control (ie, cells treated with the same emulsion but in the absence of active ingredients). As shown in Table 10, the pulsed phytol and retinol treatment resulted in significantly more production of hyaluronic acid than daily treatment regimens from active ingredients to HDF cells. Additionally, pulsed treatment with Tiliacora triandra or glycolic acid was only slightly less effective than daily treatment, despite the fact that over the entire duration of the treatment, almost half of the active ingredient was used in pulsed treatment compared to the daily treatment.
[0195] As various changes may be made to the subject matter described above without departing from the spirit and scope of the present invention, it is intended that all subject matter contained in the above description, or defined in the appended claims, be construed as descriptive and illustrative of the present invention. Many modifications and variations of the present invention are possible in light of the above instructions. Accordingly, the present description is intended to cover all such alternatives, modifications and variations included within the scope of the appended claims.

权利要求:
Claims (12)
[0001]
1. Non-therapeutic cosmetic method to reduce dermatological signs of aging in human skin, CHARACTERIZED by the fact that it comprises, in any order, the steps of (1) applying topically to an area of skin that needs it, at least once per day, a first skin treatment composition comprising, in a physiologically compatible vehicle, an effective amount of a retinoid, for a first period of time comprising from 2 to 15 days; (2) topically applying to said skin, at least once a day, a second skin treatment composition that is different from said first skin treatment composition for a second period of time comprising from 2 to 15 days in which the said second skin treatment composition comprising a moisturizer; and (3) repeat steps (1) and (2) a sufficient number of times to lessen said dermatological signs of skin aging.
[0002]
2. Method according to claim 1, CHARACTERIZED by the fact that said retinoid comprises retinol.
[0003]
3. Method according to claim 1, CHARACTERIZED by the fact that said second skin treatment composition comprises a biological extract.
[0004]
4. Method according to claim 3, CHARACTERIZED by the fact that said biological extract comprises an extract of a plant, yeast or fungus.
[0005]
5. Method according to claim 4, CHARACTERIZED by the fact that said extract of a plant, yeast or fungus comprises an extract of CO-LEUS FORSKOHLII.
[0006]
6. Method according to claim 1, CHARACTERIZED by the fact that said second skin treatment composition comprises phytol.
[0007]
7. Method according to claim 1, CHARACTERIZED by the fact that said second skin treatment composition comprises an alpha-hydroxy acid or salt thereof.
[0008]
8. Method according to claim 7, CHARACTERIZED by the fact that said alpha-hydroxy acid or salt thereof comprises glycolic acid or a salt thereof.
[0009]
9. Method, according to claim 1, CHARACTERIZED by the fact that said decrease in dermatological signs of aging is selected from the group consisting of: (a) treatment, reduction and/or prevention of expression lines and/or wrinkles; (b) skin pore size reduction; (c) improvement in skin thickness, plump appearance and/or tightness; (d) improvement in smoothness, elasticity and/or smoothness of the skin; (e) improvement in skin tone, radiance and/or clarity; (f) improvement in pro-collagen and/or collagen production; (g) improvement in elastin maintenance and remodeling; (h) improvement in skin texture and/or promotion of retexturization; (i) improvement in skin barrier function and/or repair; (j) improvement in the appearance of skin contours; (k) restoration of skin shine and/or luminosity; (l) replacement of essential nutrients and/or skin constituents; (m) improvement in skin appearance diminished by aging and/or menopause; (n) improvement in skin hydration; (o) increase in skin resilience and/or elasticity; (p) treatment, reduction and/or prevention of sagging skin; (q) improvement in skin firmness; (r) reduction of pigmented spots and/or mottled skin; and (s) improving the skin's optical properties by light reflection or diffraction.
[0010]
10. Method according to claim 1, CHARACTERIZED by the fact that said first time period is 7 days, and said second time period is 7 days.
[0011]
11. Method according to claim 1, CHARACTERIZED by the fact that said first and second periods of time are consecutive so that one starts on the day following the last day of the other.
[0012]
12. The method of claim 1, CHARACTERIZED by the fact that said second skin treatment composition does not comprise an effective amount of a retinoid.

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CN111743802B|2020-07-28|2022-02-25|广州鹰远生物科技有限公司|Composition for increasing skin elasticity and application thereof|

法律状态:
2019-10-15| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2021-03-16| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2021-05-11| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 04/03/2016, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US201562128647P| true| 2015-03-05|2015-03-05|

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US62/128,647|2015-03-05|

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PCT/US2016/020953|WO2016141315A1|2015-03-05|2016-03-04|Methods for treating skin|BR122019004464-3A| BR122019004464B1|2015-03-05|2016-03-04|method for decreasing dermatological signs of aging in human skin|