Topical compositions and methods to promote optimal dermal white adipose tissue formation in vivo

Abstract

To provide topical compositions to promote optimal dermal white adipose tissue formation in vivo, and methods to improve the appearance of skin in an individual.SOLUTION: The present invention provides a topical composition effective for improving the appearance of the skin, comprising at least one adipogenic agent, at least one lipolytic agent and at least one penetrant, wherein the improvement comprises an improvement in the appearance of insufficient volume.SELECTED DRAWING: None

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Application No. 62 / 751,222, filed October 26, 2018, which is expressly incorporated by reference herein in its entirety. FIELD OF THE PRESENT APPLICATION

[0002] The present invention relates generally to topical compositions and methods effective for promoting dermal white adipose tissue formation in vivo, comprising an adipogenesis-stimulating agent, a lipolytic agent, and at least one penetrating agent.

[0003] Sun exposure and a high-fat or high-carbohydrate diet can cause loss of dermal fat cells, resulting in volume loss or the appearance of hollows in certain areas of the skin. Sun exposure and a high-fat or high-carbohydrate diet can cause hypertrophy of dermal fat cells, weakening the skin and causing sagging skin. Loss and hypertrophy of dermal fat cells can occur in the same area or in adjacent areas.

[0004] Existing pharmaceutical and cosmetic approaches to promote dermal adipogenesis do not adequately address the dual concerns of adipocyte loss and hypertrophy. These approaches focus on increasing adipocyte volume and do not consider the potential for hypertrophy. In addition, agents that promote the conversion of preadipocytes to adipocytes generally promote lipid accumulation by the newly converted cells. In addition, increasing adipocyte number through adipogenic stimulation is more difficult and occurs more slowly than increasing adipocyte volume. Sustained use of agents that promote preadipocyte conversion and increase adipocyte volume may induce or exacerbate adipocyte hypertrophy.

[0005] Those who would use compositions that promote both the conversion of preadipocytes to adipocytes and the accumulation of lipids by the newly converted adipocytes face two important challenges. First, the user must carefully administer the agent only to areas of the skin that require increased volume, and not to areas that do not. Second, the user must only use adipogenic ingredients when there are insufficient numbers of dermal adipocytes, otherwise there is a risk of excessive adipocyte enlargement, which can cause adipocyte hypertrophy and weaken the skin and cause sagging.

[0006] The first requirement is particularly difficult to meet with respect to the face, where there is an overlap between areas containing volume deficits due to loss of adipocytes and areas containing hypertrophic adipocytes. This is particularly true for the periorbital area, where the loss of volume in the tear trough is accompanied by sagging skin containing hypertrophic adipocytes that manifests as eye bags, but also for other areas of the face.

[0007] Existing pharmaceutical and cosmetic approaches that attempt to improve skin appearance by delivering adipogenic components to dermal white adipose tissue have not faced the problem of overlapping areas of adipocyte loss and adipocyte hypertrophy and have not been studied in the human face.

[0008] The second requirement is also difficult for users to comply with. There are individual differences in the extent of adipocyte loss. There are also differences in the rate at which dermal white adipose tissue responds to treatment with the adipogenic component. In addition, there may be individual differences in the amount of adipogenic component used. These differences make it difficult for manufacturers to advise users as to when administration should be discontinued.

[0009] Existing pharmaceutical and cosmetic approaches that attempt to improve skin appearance by delivering adipogenic components to dermal white adipose tissue do not face the problem of inducing or exacerbating adipocyte hypertrophy, and because these approaches have not been evaluated for a sufficient period of time, the potential for hypertrophy and resulting sagging cannot be assessed.

[0010] We previously reported inventions that improve the structure, function, and health of dermal white adipose tissue exposed to UV damage by enhancing adipogenesis in vivo (see, e.g., U.S. Provisional Application No. 62 / 555,919, filed September 8, 2017, and U.S. Provisional Application No. 62 / 694,723, filed July 6, 2018). In those inventions, we identified optional ingredients that we believe can further increase adipogenesis by, for example, synergistically increasing PPARy expression to amplify PPARy signaling.

[0011] In the present invention, we have surprisingly found that an ingredient that we expected to increase the expression of PPARy and induce lipid signaling actually has the opposite effect of inducing lipolysis. Even more surprisingly, we have found that a topical composition combining this ingredient with a drug that has been shown to specifically promote adipogenesis can selectively increase adipogenesis while increasing lipolysis in areas where lipolysis is beneficial. Furthermore, this topical composition may be applied broadly to the skin without selectively targeting the areas that require adipogenesis or lipolysis.

[0012] Here, we demonstrate a method for treating skin volume defects that addresses the concerns of both insufficient adipocyte numbers and excess adipocyte volume. For the first time, we have shown that a composition containing a combination of agents capable of adipogenesis and lipolysis effectively restores volume in areas of skin that require it. Furthermore, the treatment improves the appearance of sagging skin, while showing no or a positive effect on adipocyte volume.

[0013] Our results were obtained in a study on the most relevant and challenging keratinous surface, namely human facial skin, including the most challenging sun-exposed periorbital area. The effectiveness of our method and composition was evaluated using 3D digital spectrometry, the most significant instrument for evaluating volumetric changes. Furthermore, our study has followed subjects for over 9 months, the time it is possible to detect whether the resulting lipogenesis leads to an undesirable increase in the volume of dermal adipocytes, which would manifest as sagging skin.

[0014] It has been shown for the first time that a single topical composition can selectively increase dermal fat volume in vivo in areas of the skin that require lipogenesis, while simultaneously preventing excess lipogenesis and decreasing dermal fat volume in areas where it is desired to decrease lipogenesis.Furthermore, it has been shown for the first time that a single topical composition can selectively decrease dermal fat volume in areas where it is desired to decrease lipid fat volume, while simultaneously preventing excess lipolysis and increasing dermal fat volume in areas where it is desired to increase dermal fat volume.Others have shown that the ingredients that provide lipolytic activity to topical compositions have lipolytic activity both in vitro and in vivo, and that in vitro activity is due to the promotion of lipase function. Summary of the Invention

[0015] In one embodiment of the present invention, a topical composition is provided that is effective in improving the appearance of skin, the topical composition comprising at least one adipogenic component, at least one lipolytic agent, and at least one penetrating agent, where improvement refers to an improvement in the appearance of a volume defect. In some embodiments, the improvement in the appearance of a volume defect occurs without causing an increase in the appearance of excess volume. In some embodiments, the improvement in the appearance of a volume defect occurs with an improvement in the appearance of sagging. In some embodiments, the improvement in the appearance of a facial appearance occurs. In some embodiments, the improvement in the appearance of a volume defect comprises an increase in volume in the periorbital area. In some embodiments, the improvement in the appearance of a volume defect comprises an increase in volume along the cheekbones. In some embodiments, the improvement in the appearance of a volume defect comprises an increase in volume in the upper cheek. In some embodiments, the improvement in the appearance of sagging comprises a decrease in volume in the lower cheek proximal to the nasolabial fold. In some embodiments, the improvement in the appearance of sagging comprises an increase in volume in the upper cheek below the cheekbones. In some embodiments, the improvement in the appearance of sagging comprises an increase in volume in the mid-cheek area.

[0016] In one embodiment of the present invention, a topical composition effective for improving the appearance of skin is provided, the topical composition comprising at least one adipogenic component, at least one lipolytic agent, and at least one penetrating agent, wherein the improvement comprises improving the appearance of sagging skin.

[0017] In one embodiment of the present invention, a topical composition effective for preventing skin damage due to sun exposure, weight gain, weight loss or physical exercise is provided, the topical composition comprising at least one adipogenic component, at least one lipolytic agent, and at least one penetrating agent, wherein the damage to be prevented is associated with a reduction in the number of dermal adipocytes and their hypertrophy.

[0018] In one embodiment of the present invention, a topical composition effective to selectively promote an increase or decrease in subcutaneous fat volume as needed is provided, the topical composition comprising at least one adipogenic component, at least one lipolytic agent, and at least one penetrating agent.

[0019] One embodiment of the present invention is a topical composition effective to selectively promote loss or gain of dermal fat volume as needed, comprising a mixture of an adipogenic component, a lipolytic agent, and at least one penetrating agent.

[0020] In another embodiment of the present invention, there is provided a method of promoting optimal dermal white adipose tissue formation in an individual in need thereof, the method comprising topically applying to a target skin area of ​​the individual a composition comprising a mixture of an adipogenesis promoter, a lipolytic agent, and at least one penetrating agent.

[0021] In one embodiment of the present invention, a method for improving the appearance of an individual's skin is provided, the method comprising topically applying to the skin a composition containing at least one agent having lipolytic activity, at least one agent having adipogenic activity, and at least one penetrating agent. In some embodiments, a combination of agents having lipolytic and adipogenic activity is included in a single composition. In some embodiments of the present invention, the lipolytic agent having lipolytic activity is included in a composition separate from the composition containing the adipogenic component having adipogenic activity. In some embodiments of the present invention, the topical application of the two separate compositions occurs in close time proximity or as part of a combined treatment form. In other embodiments of the present invention, the composition is applied to overlapping areas of a keratin-based skin surface. In other embodiments of the present invention, the composition is applied to sun-exposed areas. In a preferred embodiment, the composition is applied to the face. In some embodiments of the present invention, after application of the composition, there is a visible reduction in the appearance of hollowing. In other embodiments of the present invention, after application of the composition, there is a visible reduction in the appearance of volume defects. In other embodiments of the present invention, after application of the composition, there is a visible reduction in the appearance of sagging or excess volume, or both. In other embodiments of the present invention, the improvement in skin appearance is partially necessitated by sun exposure, weight loss, weight gain, or physical exercise. In some embodiments of the present invention, after application of the composition to the periorbital area, cheekbone area, or upper cheek area of ​​the face, there is a visible reduction in the appearance of hollows on the face. In some embodiments of the present invention, there is a visible reduction or improvement in the appearance of sagging at the end of the cheekbone area, the periorbital area, the upper cheek, the lower cheek, or the jawline.

[0022] In one embodiment of the present invention, there is provided a method of treating or preventing the appearance of defective skin by employing a combination of an adipogenic component and a lipolytic agent, such treatment or prevention involving the use of two or more compositions separately comprising a lipolytic agent and an adipogenic component, wherein the compositions comprising the lipolytic agent and the adipogenic component can be applied to the same area of ​​skin.

[0023] In one embodiment of the present invention, a method is provided for increasing the appearance of volume in areas of the skin where an individual needs it, and for decreasing the appearance of volume in areas of the skin where the same individual needs it, the method comprising topically applying to an area of ​​the skin of the individual a composition comprising an adipogenic component, a lipolytic agent and at least one penetrating agent.

[0024] In one embodiment of the present invention, there is provided a method for increasing the appearance of volume in areas of the skin where an individual requires it, without increasing the appearance of volume in areas of the skin where the same individual does not require it, the method comprising topically applying to an area of ​​the skin of the individual a composition comprising an adipogenic component, a lipolytic agent and at least one penetrating agent.

[0025] In other embodiments of the present invention, there is provided a method for reducing the appearance of volume in areas of the skin in which an individual requires it, without reducing the appearance of volume in areas of the skin in which the same individual does not require it, the method comprising topically applying to an area of ​​the skin of the individual a composition comprising an adipogenic component, a lipolytic agent and at least one penetrating agent.

[0026] In one embodiment of the present invention, a method for increasing the volume of adipose tissue in an area of ​​the skin where an individual needs it and for decreasing the volume of adipose tissue in an area of ​​the skin where the same individual needs it comprises topically applying to the area of ​​the skin of the individual a composition comprising an adipogenic component, a lipolytic agent and at least one penetrating agent.

[0027] Other objects, advantages, and novel features of the present invention will be readily apparent to those skilled in the art. Other objects and features of the present invention will be ascertained from the following detailed description of one or more preferred embodiments, when considered in conjunction with the drawings presented. It should be recognized that one or more examples in this disclosure are non-limiting examples, and the present invention is intended to encompass variations and equivalents of these examples. This disclosure is written for those skilled in the art. This disclosure uses terms and acronyms that may not be familiar to laymen, but those skilled in the art will be familiar with the terms and acronyms used herein. [Brief description of the drawings]

[0028] The description herein will be more fully understood in view of the following drawings.

[0029] [Figure 1] FIG. 1 illustrates the different skin layers of epidermis, dermis and adipose in humans and the process for promoting optimal composition of dermal white adipose tissue.

[0030] [Diagram 2]FIG. 2 shows before (FIG. 2A) and after (FIGS. 2B, 2C, and 2D) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention.

[0031] [Diagram 3] Figure 3 shows the same before (Figure 3A) and after (Figures 3B, 3C and 3D) photographic images as Figures 2A, 2B, 2C and 2D, respectively, the only difference being that a different viewpoint has been chosen.

[0032] [Figure 4] Figure 4 shows before (Figures 4A and 4B) and after (Figures 4C and 4D) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention. Figure 4E is a bar graph showing the reduction in area of ​​skin grooves.

[0033] [Diagram 5] FIG. 5 shows before (FIG. 5A) and after (FIG. 5B) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention.

[0034] [Figure 6] Figure 6 shows before (Figures 6A, 6B, and 6C) and after (Figures 6D, 6E, and 6F) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention. Quantification of the difference between the before and after images is shown in Figure 6G (Figure 6B vs. 6E) and Figure 6H (Figure 6C vs. 6F).

[0035] [Figure 7]Figure 7 shows before (Figures 7A, 7B, 7C, 7D, and 7E) and after (Figures 7F, 7G, 7H, 7I, and 7J) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention. Quantification of the differences between the before and after images is shown in Figure 7K (Figure 7B vs. 7G), Figure 7L (Figure 7C vs. 7H), Figure 7M (Figure 7D vs. 7I), and Figure 7N (Figure 7E vs. 7J).

[0036] [Figure 8] Figure 8 shows before (Figures 8A, 8B, and 8C) and after (Figures 8D, 8E, and 8F) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention. Quantification of the difference between the before and after images is shown in Figure 8G (Figure 8B vs. 8D) and Figure 8H (Figure 8C vs. 8E).

[0037] [Figure 9] Figure 9 shows before (Figures 9A, 9B, and 9C) and after (Figures 9D, 9E, and 9F) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention. Quantification of the difference between the before and after images is shown in Figure 9G (Figure 9B vs. 9D) and Figure 9H (Figure 9C vs. 9E).

[0038] [Figure 10] Figure 10 shows before (Figures 10A, 10B, 10C, and 10D) and after (Figures 10E, 10F, 10G, and 10H) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention. Quantification of the differences between the before and after images is shown in Figure 10I (Figure 10B vs. 10F), Figure 10J (Figure 10C vs. 10G), and Figure 10K (Figure 10D vs. 10H).

[0039] [Figure 11]Figure 11 shows before (Figures 11A, 11B, and 11C) and after (Figures 11D, 11E, and 11F) photographic images taken with an Antera digital camera of an individual undergoing treatment with a topical composition according to one embodiment of the present invention. Quantification of the difference between the before and after images is shown in Figure 11G (Figure 11B vs. 11D) and Figure 11H (Figure 11C vs. 11E).

[0040] Detailed explanation

[0041] All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs, unless otherwise defined.

[0042] The term "invention" or "present invention" as used herein is a non-limiting term and is not intended to refer to a single aspect of a particular invention, but rather encompasses all possible aspects described in the present specification and claims. As used herein, the term "optimal" or "necessary" in conjunction with the term "adipogenesis" refers to the need to replenish or restore the number of adipocytes in dermal white adipose tissue exposed to ultraviolet light that causes a decrease in the number of adipocytes. As used herein, the term "excessive" in conjunction with the term adipogenesis refers to a state of dermal white adipose tissue that can reduce the volume of adipocytes contained in said dermal white adipose tissue.

[0043] The patent literature describes a number of compositions that have been shown to stimulate adipogenesis or, conversely, stimulate lipolysis in vitro.

[0044] The present invention surprisingly identifies a single composition that promotes both adipogenesis and lipolysis in dermal white adipose tissue, where the adipogenic and lipolytic effects of the composition do not cancel each other out.As used herein, the term "adipogenesis" refers to the increase in the number of adipocytes due to the conversion of cells into the adipocyte lineage and the increased differentiation of adipose-derived stem cells, and the subsequent accumulation of fat by these cells.As used herein, the expression "lipolysis" refers to the reduction in the amount of fat stored in mature adipocytes.Now, for the first time, it has been shown that a single composition can promote adipogenesis and lipolysis in a context-specific manner.Using 3D photography over time, it has been shown that adipogenesis and lipolysis are independently effective in adjacent regions of dermal white adipose tissue.

[0045] composition

[0046] In one aspect of the invention, the present disclosure relates to a topical composition effective for promoting adipogenesis and inducing lipolysis in dermal white adipose tissue in vivo, comprising an active ingredient having adipogenic activity, an active ingredient having lipolytic activity, and at least one penetrating agent.

[0047] In another aspect of the invention, the invention uses a penetrating agent to deliver components having adipogenic and lipolytic activity through the epidermis to the skin in a manner effective to achieve a safe and effective dose. As used herein, a "safe and effective dose" is intended to mean an amount of a ready-to-use composition sufficient to either: i) ameliorate one or more symptoms of a disease; or (ii) produce one or more favorable cosmetic effects. Furthermore, the ready-to-use composition, when applied topically, is painless and does not cause irritation, skin reaction, inflammation, or allergic reaction. As used herein, a "penetrating agent" refers to an agent that promotes penetration into the skin. Once the composition reaches the dermis, the adipogenic components enter resident preadipocytes and are transferred to the cell nucleus to signal via peroxisome proliferator-activated receptor gamma (PPARy) to convert the cells to the adipocyte lineage, and once in the dermis, the lipolytic components enter resident mature adipocytes to release fat. PPARy is known to regulate fatty acid storage and glucose metabolism. PPARy is also known to control adipocyte differentiation. Lipolytic compounds enter fat cells and stimulate intracellular lipases to break down stored triacylglycerol and release fatty acids. There are two types of intracellular lipases: adipose tissue triglyceride lipase and hormone-sensitive lipase. These lipases are regulated by hormones and chemicals.

[0048] Figure 1 shows the different skin layers of the human epidermis, dermis, and subcutaneous tissue. Also shown in Figure 1, the process for promoting dermal white adipose tissue (dWAT) structure and function begins with the delivery of the composition of the present invention to PPARy receptor ligands through the dermis. The dermis is composed of three main types of cells: fibroblasts, macrophages, and adipocytes. PPARy receptor ligands signal preadipocytes to convert into adipocytes. The newly converted adipocytes restore subdermal white adipose tissue lost due to sun exposure and weight gain.

[0049] In a preferred embodiment of the invention, the adipogenic component comprises an unsaturated fatty acid selected from the group consisting of C18:1, C18:2, C18:3, C18:4, C20:1, C20:3, C20:4, C20:5, C22:1, C22:4, C22:6, C24:1, and unsaturated derivatives and mixtures thereof. As defined herein, fatty acids are described by the total number of carbon atoms (subscript) followed by the total number of double bonds. For example, "C18:1 fatty acid" is intended to mean a C18 fatty acid with one double bond, such as oleic acid. "C18:2 fatty acid" is intended to mean a C18 fatty acid with two double bonds, such as linoleic acid. "Unsaturated fatty acid" means a fatty acid with one or more double bonds in the fatty acid chain, including monounsaturated and polyunsaturated fatty acids. For example, "unsaturated C18 fatty acid" may refer to one or more C18 fatty acids selected from the group consisting of oleic acid, linoleic acid, a-linolenic acid, g-linolenic acid, conjugated linoleic acid and their isomers. In another preferred embodiment of the present invention, the unsaturated C18 and C24 fatty acids may be selected from the group consisting of oleic acid, linoleic acid, a-linolenic acid, g-linolenic acid, dihomo-y-linolenic acid, arachidonic acid, stearidonic acid, eicosapentaenoic acid, docosahexaenoic acid, dihomo-y-linolenic acid, docosatetraenoic acid, vaccenic acid, paulic acid, elaidic acid, gondoic acid, erucic acid, nervonic acid, and their derivatives and mixtures. In other preferred embodiments, the topical compositions of the present invention can include naturally occurring unsaturated fatty acids, such as those selected from the group consisting of sunflower oil, grape seed oil, kukui oil, canola oil, evening primrose oil, chia oil, hemp oil, wheat germ oil, soybean oil, sesame oil, borage oil, blackcurrant oil, cottonseed oil, safflower oil, corn oil, and mixtures thereof. In other preferred embodiments, the adipogenic component can include medicinal plants, such as an extract of Krachaidam.

[0050] In a preferred embodiment of the present invention, the adipogenic component is selected from the group consisting of acreatin, ascorbic acid, black soybean extract, chlorogenic acid, cinnamon extract, cinnamon extract, cinnamon tannin B1, bitter orange extract, Lomatium suksdorfii extract, melatonin, phytol, sinensetin, scutellaria leaf extract, and citrus arbutus extract.

[0051] In a preferred embodiment of the present invention, the adipogenic component is selected from the group consisting of (2S)-7,4'-dihydroxy-8-prenylflavan, Morus yunnanensis extract, 3-butylhydroxyanisole, 4-methoxychalcone, Anemone annuus extract, Artemisia santolinifolia extract, Artemisia santolinifolia, Babakin, Sugarcane extract, Melastomataceum extract, Piper chabai fruit extract, Phloretin, Hollandaea fruit extract, Sage extract, Sakuranetin, Sarsapogenin, Tenyokenkoushi extract, Vanadium, and the like.

[0052] In a preferred embodiment of the present invention, the adipogenic component is selected from the group consisting of: 10-oxo-12(Z)-octadecenoic acid, 13-Oco-9(Z),11(E),15(Z)-octadecatrienoic acid, 15-(S)-hydroxyeicosatetraenoic acid, acrylamide, Bidens extract, Brazilian red propolis extract, butylated hydroxyanisole, chebulazinic acid, Chlorella vulgaris extract, Silybum thistle extract, cyanidin-3-glucoside, daidzein, diallyl disulfide, Echinacea purpurea root extract, emodin, flavanones, furan fatty acid 9M5, geranylgeraniol, ginsenoside 20S-protopanaxatriol, ginsenoside Rbl, ginsenoside Re, ginsenoside Rh2, glabridin, Heracleum dissectum Lebb Extract, Hydrogen Sulfide, Illicium Vulgare Extract, Obliquus Obliquus Extract, Isoimperatorin, Lactic Acid, Lecithin, Licorice Extract, Loquat Extract, Moringa Concanensis Nimmo Extract, N-Oleyl Glycine, N. Nouchali Seed Extract, Norwogonin, Notopterygium Incisum Root Extract, Palmitoyl Lactate, Pentamethylquercetin, Phenyl Lactate, Quinine, Retrofractamide A, Rheum Palmatum L Rhizome, S-Adenosylmethionine, Sangennol F, Scutellaria Baicalensis Extract, Soybean Pinitol, Spermidine, Tectochrysin, Myrobalan Fruit Extract, Tetracera Indica merr.) extract, tetramethylkaempferol, umbelliferone, wakame extract, vitamin B3 and vitamin B6.

[0053] In a preferred embodiment of the present invention, the lipolytic component comprises a medicinal plant, such as black ginger extract.

[0054] In a preferred embodiment of the invention, the lipolytic agent is selected from the group consisting of ascorbic acid, butyrate, chrysanthemum extract, chlorogenic acid, bitter orange extract, eicosapentaenoic acid, gallic acid, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, INDUS810, black ginger extract, lycopene, magnolol, magnolia bark extract, Japanese mulberry extract, pueraria lobata root extract, resveratrol, Schisandra chinensis extract, sodium butyrate, Solenostemma argel extract, Mizurembu extract, T. foenum graecum seed extract, triphenyl phosphate and tyramine.

[0055] In a preferred embodiment of the present invention, the lipolytic agent is selected from the group consisting of 3-iodothyronamine, Aelenia baicalensis leaf extract, Anoectochilus formosanus extract, arginine, Brussels sprout extract, brucein A, brucein B, brucein C, 3'-hydroxybrucein A, brusatol, bruceanthinol, Scutellaria baicalensis seed extract, Centella asiatica leaf extract, Cannabis sativa extract, Cyclopia maculata extract, fermented castanea crenata inner shell extract, forskolin, Sanshin extract, genipin, Hemerocallis fulva extract, Manchuria walnut extract, Licarin A, Lychee fruit extract, magnesium, malic acid, okadaic acid, Paecilomyces hepiali mycelium extract, palmitoleic acid, Phaseolus vulgaris extract, Posidonia oceanica (L.) delile) Extract, Salacia (S.) reticulata Extract, Sea Cucumber Saponin Echinosidoside A, Sarmientobar Bark Leaf Extract, Soy Hydrolysate, Soyasapogenol A, Soyasapogenol B, Octopamine, N-Methyltyramine, Purple Myrtles, TAT-Glycine-Lysine-Histidine Complex, Terminalia Sericea Extract, Chanqing Extract, Zanthoxylum Indicum Seed Oil.

[0056] In a preferred embodiment of the present invention, the lipolytic agent is selected from the group consisting of acetyl-keto-p-boswellic acid, aged black garlic extract, almond skin extract, andiroba extract, apigenin, apple extract, artemisia anguic extract, Astilbe chinensis Franch. et Savet. extract, birch bark, platyphylloside, berberine, bergamottin, betulinic acid, bilobalide, black bean extract, black tea extract, Brassica campestris spp.rapa root extract, caffeine, capsanthin, capsicum seed oil, capsaicin, carnitine, chitosan, chrysophanol, cinnamaldehyde, sirsimarin, korean thistle (Cirsium setidens nakai) extract, bergamot extract, satsuma mandarin extract, clove extract, coffee extract, Commiphora mukul, crocin, kabocha extract, turmeric extract, honeybush (Cyclopia intermedia), epigallocatechin gallate, euglena, eurycomanone, nagaekasa extract, fucoidan, fucoxanthin, bladderwrack (Fucus vesiculosus) extract, garcinia gummi-gutta extract, Agarwood extract, Genistein, Germinated soy protein hydrolysate, Ginkgo biloba extract, Ginsenoside Rgl, Gomisin, Grape seed extract, Grape skin extract, Green tea extract, Kanamugura, Hydroxytyrosol, Hydroxysafflor Yellow A, Isopropylnorsynephylline, Kaempferol, Korean Chungtaejeon tea extract, Lipoic acid, Lotus leaf extract, Lotus seed extract, Luteolin, Lysimachia foenum-graecum extract Moringa Seed Extract, Morusin, Banana Pulp Extract, Myricanol, Naringenin-7-O-Glucoside, New Zealand Blackcurrant Extract, Oleanolic Acid, Oleoresin Capsicum, Oleuropein, P-Synephrine, Pear Pomace Extract, Ume Extract, Buckwheat, Pterostilbene, Pycnogenol, Quercetin, Quinic Acid, Raspberry Ketone, Rubus Fruticosus Extract, Purple Sweet Potato Extract, Rutin, Scutellaria Baicalensis Extract, Sericoside, Sinensetin, Spilanthol, Stem Bromelain Extract, Ginseng Extract, Synephrine, Syringic Acid, Tanshinone IIA, Dandelion Extract, Triamcinolone Acetonide, Ursolic Acid, Vitamin D, Widrol, Xansigen, Xanthohumol.

[0057] In a preferred embodiment of the present invention, the topical compositions of the present invention comprise from about 5% (w / w) to about 40% (w / w), preferably from about 10% (w / w) to about 30% (w / w), of a source of unsaturated fatty acids whose carbon chains are predominantly (e.g., 30% or more of the total) of carbon chain length 18 or greater. As used herein, the abbreviation "(w / w)" refers to true weight percentages, i.e., the weight of the component divided by the total weight of the composition to convert to a percentage.

[0058] In some embodiments, the topical compositions of the present invention contain about 5% (w / w) to about 40% (w / w), preferably about 10% (w / w) to about 30% (w / w), of a source of unsaturated fatty acids in which the carbon chains are predominantly (e.g., 30% or more of the total) of carbon chain length 18 or greater. As used herein, the abbreviation "(w / w)" refers to true % by weight, i.e., the weight of the component divided by the total weight of the composition to convert to a percentage.

[0059] In a preferred embodiment of the invention, the penetrant is selected from the group consisting of urea, imidourea, palmitate, isopropyl palmitate, isopropyl myristate, propylene glycol, and non-ionic detergents.

[0060] In some embodiments, the topical compositions of the present invention comprise from about 5% (w / w) to 25% (w / w), preferably from about 7% (w / w) to 15% (w / w) of a penetrating agent.

[0061] In some embodiments, the topical composition of the present invention may optionally contain about 0.1% (w / w) to about 25% (w / w), preferably about 0.1% (w / w) to about 5% (w / w), of hyaluronic acid. More preferably, about 0.1% (w / w) to about 1.0% (w / w). Hyaluronic acid is a natural glycosaminoglycan that is widely distributed in human connective tissues, epithelial tissues, nervous tissues, etc. Hyaluronic acid is known to have water-binding and water-attracting properties that allow it to fill the gap between collagen and elastin, which are connective fibers, in the dermis. It has a molecular weight of 50,000 daltons or more and forms a highly viscous solution. In one embodiment of the present invention, the form of hyaluronic acid is selected from the group consisting of hyaluronic acid, including its salts, analogs, modifications, and derivatives. In one embodiment, the form of hyaluronic acid is sodium hyaluronate or potassium hyaluronate. Potassium hyaluronate and sodium hyaluronate are water-soluble salts of hyaluronic acid.

[0062] In one embodiment of the present invention, the weight percentage of the adipogenic component present in the topical composition is greater than the weight percentage of the lipolytic agent present in the topical composition.

[0063] In some embodiments of the present invention, the topical composition further comprises an agent having indirect adipogenic activity. In some embodiments of the present invention, the topical composition further comprises an agent having indirect lipolytic activity.

[0064] The topical compositions described herein may further comprise additional and other optional ingredients known to be useful in personal care formulations.

[0065] Generally, a topical composition includes a carrier.

[0066] In some embodiments, the topical composition is preferably a liquid composition that contains water as a carrier.The suitable amount of water can be about 0.1% to about 99.9% by weight of the composition.More typically, the amount of water can be about 40% to about 99.9% by weight of the composition.Preferably, the amount of water can be about 60% to about 99.9% by weight of the composition.

[0067] In other embodiments, the topical composition comprises at least one active ingredient and a hydrophobic carrier.Suitable hydrophobic carriers can be, for example, natural oils, synthetic oils, and combinations thereof.Other hydrophobic carriers will be known to those skilled in the art.

[0068] The topical composition may further comprise a skin soothing agent. As used herein, "skin soothing agent" refers to a compound that reduces or prevents skin irritation. Suitable skin soothing agents include, for example, plant extracts such as calendula, chamomile, aloe, comfrey, cornflower, etc., actives such as allantoin, bisabolol, panthenol, beta-glucan, colloidal oatmeal, and SymCalmin® (e.g., butylene glycol, pentylene glycol, hydroxyphenylpropamidobenzoic acid), available from Symrise, SEPICALM TM (including sodium palmitoyl proline, Nymphaea alba flower extract (commercially available from Seppic)).

[0069] The topical composition may further comprise a humectant. The humectant may promote hydration of the skin, particularly the epidermis and dermis. Suitable humectants may be, for example, glycerol, glycerin, lactic acid, urea, aloe vera, betaine, propanediol, propylene glycol, butylene glycol, and combinations thereof.

[0070] The topical composition may further include an emulsifier, in particular an emulsifier that forms a liquid crystal network or a liposomal network. Suitable non-limiting exemplary emulsifiers include, for example, OLIVEM® 1000 (including, for example, cetearyl-olivate and sorbitan-olivate (commercially available from HallStar Company)), Arlacel ... TM LC (including, for example, sorbitan stearate and sorbitan laurate (available from Croda)), CRYSTALCAST® MM (including, for example, beta sitosterol, sucrose stearate, sucrose distearate, cetyl alcohol, stearyl alcohol (available from MMP Inc.)), UNIOX CRISTAL (including cetearyl alcohol, polysorbate 60, cetearyl glucoside (available from Chemyunion) and the like). Other suitable emulsifiers include lecithin, hydrogenated lecithin, lysolecithin, phosphatidylcholine, phospholipids, and combinations thereof. In a preferred embodiment, the topical composition includes an emulsifier derived from cellulose, such as methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, and mixtures thereof. A suitable amount of emulsifier can be about 0.4% to about 1.75% by weight of the composition.

[0071] Additionally, topical compositions may also include triethanolamine (TEA), diethanolamine (DEA), and ethanolamine, which are commonly used to aid in the formation of emulsions.Suitable amounts of triethanolamine (TEA), diethanolamine (DEA), or ethanolamine added may range from about 0.4% to about 1.75% by weight of the composition.

[0072] The topical composition may further include a cross-linked polyacrylate polymer, which functions as an emulsion stabilizer or as a viscosity enhancer, such as Carbomer® 934, Carbomer® 940, Carbomer® 980, Carbomer® 990, and Carbomer® 996. A suitable amount of the cross-linked polyacrylate polymer may be from about 0.5% to about 5% by weight of the composition.

[0073] The topical composition may further comprise a preservative to maintain stability. The preservative may also prevent the growth of microbial organisms in the composition. Suitable preservatives are known in the art and include, for example, methylparaben, phenoxyethanol, capryl glycol, glyceryl caprylate, benzoic acid, sorbic acid, gallic acid, propylparaben, butylated hydroxytoluene (BHT), Oxyprotect, euxyl® products, and combinations thereof. Other suitable preservatives will be known to those skilled in the art. A suitable amount of preservative may be about 0% to about 7% by weight of the composition.

[0074] The topical composition may further comprise a pH adjusting agent to control / maintain the pH of the composition within the range of the skin pH.

[0075] The topical composition may further comprise fragrances, scents, dyes, surfactants, emollients, antioxidants, rheology modifiers, film formers, and other ingredients known to be useful in personal care formulations. Suitable surfactants may be, for example, Brij® 20, Brij® 28, Brij® 98, Brij® 99. A suitable amount of surfactant may be about 0.25% to about 1% by weight of the composition. Suitable emollients may be, for example, alcohol-based emollients such as isopropyl palmitate or isopropyl myristate. A suitable amount of emollients may be about 1% to about 7% by weight of the composition.

[0076] How to use

[0077] In another aspect of the invention, the disclosure is directed to a method of modulating dermal white adipose tissue structure, function, and health in an individual in need thereof, comprising the steps of: topically applying a composition comprising an adipogenic component, a lipolytic component, and at least one penetrating agent to a targeted skin area of ​​the individual. The targeted skin area is not limited to a discrete area requiring adipogenesis or, conversely, an area requiring lipolysis, but rather, the composition can be administered to a broad area of ​​skin incorporating both areas requiring adipogenesis and areas requiring lipolysis.

[0078] In another aspect of the invention, the present disclosure is directed to a method of increasing adipogenesis in a discrete area of ​​the skin of an individual in need thereof without causing a general increase in adipogenesis, comprising topically applying a composition comprising an adipogenic component, a lipolytic component and at least one penetrating agent.

[0079] In another aspect of the invention, the present disclosure is directed to a method of increasing lipolysis in a discrete area of ​​the skin of an individual in need thereof without causing a general increase in lipolysis, comprising topically applying a composition comprising an adipogenic component, a lipolytic component and at least one penetrating agent.

[0080] The topical composition can be applied to the target skin area by any suitable delivery vehicle. For example, the composition can be applied as a lotion, wash, gel, ointment, cream, solid stick, or foam. Additionally, the composition can be applied using a wipe, using a mitt or glove, using an aerosol dispenser, using a pump spray, using a trigger spray, using a squeeze bottle, or using a mask.

[0081] The composition can be applied daily, every other day, every 2-3 days, every week, every month, and every other year, as desired. The composition can be applied multiple times a day, multiple times a week, or multiple times a month. In one embodiment, the composition is applied regularly for at least 6 weeks. In another embodiment, the composition is applied at least twice a day.

[0082] In some embodiments, the composition of the present disclosure can be used together with additional skin care compositions as part of skin care regimen.For example, in face treatment and care.In the present disclosure, it should be understood that at least one of the products of the regimen comprises the topical composition of the present disclosure, thereby providing the advantage of promoting the structure and function of dermal white adipose tissue.

[0083] Although a skin care system is described herein, those skilled in the art should understand that the regimen using the compositions of the present disclosure can be used in a variety of other daily regimens that consist of steps to cleanse, treat, moisturize and protect the skin. It is understood that a skin care regimen may combine all or some of these steps, or multiple repetitions of the same steps, to achieve the desired effect on the skin.

[0084] Other objects, advantages, and novel features of the present invention will be apparent from the foregoing detailed description of one or more preferred embodiments, examples, and aspects. It should be recognized that the one or more examples in this disclosure are non-limiting examples, and that the present invention is intended to encompass modifications and equivalents of these examples. EXAMPLES

[0085] Example 1

[0086] Preparation of a topical composition according to one embodiment of the present invention.

[0087] Various components according to the amounts shown in Table 1 were uniformly dispersed and dissolved to obtain a composition, which was then stirred to obtain a lotion.

[0088] [Table 1]

[0089] Example 2

[0090] 2A, 2B, 2C and 2D show pre- and post-treatment photographic images of an individual treated with a topical composition according to the invention. The topical composition according to the invention was applied to a large area from under the right eye down the cheek to the right corner of the mouth. The treatment period was 74 days, with applications at least twice a day. The photographs were taken with an Antera digital camera system that does not rely on natural light but creates its own light source. No image manipulation was performed. The increase in lipogenesis is reflected in the resolution of a discrete depression in the upper left corner of the right cheek. This depression is reduced in appearance at 29 days of use (Fig. 2B compared to Fig. 2A). After 40 days of use, there is a further reduction in the appearance of this depression (Fig. 2C compared to Fig. 2B). The improvement in the appearance of the depression is maintained at 74 days of use (Fig. 2D compared to Fig. 2B).

[0091] Example 3

[0092] Figures 3A, 3B, 3C, and 3D are the exact same photographic images as Figures 2A, 2B, 2C, and 2D, but from different perspectives, specifically depicting the profile of the face from the side of the head, looking inwards towards the nose. The Antera 3D digital camera system allows the user to select any perspective of the captured image by rotating and tilting the image. Figure 3B shows an increase in volume in the individual depressions depicted in Figure 2B and an overall fullness of the cheek contour compared to Figure 3A. Figure 3C shows a smoother cheek contour compared to Figure 3B. Figure 3D shows a clearly different contour of the cheek compared to Figure 3C.

[0093] Example 4

[0094] Figures 4A, 4B, 4C and 4D show before and after photographic images of the individual depicted in Figures 2A, 2B, 2C and 2D. The before photographs (Figure 4A in natural mode, Figure 4B in very large dimple mode) show the periorbital area of ​​the right eye before starting treatment with a topical composition according to the invention. The topical composition was applied for 85 days. The photographs were taken with an Antera 3D camera (which generates a unique consistent light source and automatically compares the same selection across multiple images). The dimple depths were quantified and topographically represented in colors ranging from white (no dimples) to yellow, green, blue and purple (largest dimples). No image manipulation was performed. The images taken with the Antera 3D camera (Figure 4D compared to Figure 4B) show a 46% reduction in the volume (mm3) of skin sulci with a lateral size of 7 mm or less, as reported in the bar graph depicted in Figure 4E. The Antera 3D camera system classifies dimples with a lateral size of 7 mm or less as "very large". Figures 4A, 4B, 4C, and 4D show an increase in periorbital volume in the right eye (e.g., a decrease in the area of ​​the cavity), while there is a selective decrease in volume along the cheek contour depicted in Figures 3A, 3B, 3C, and 3D.

[0095] Example 5

[0096] 5A and 5B show pre- and post-treatment photographic images of an individual treated with a topical composition according to the present invention. The topical composition according to the present invention was applied to the left cheek. The treatment period was about 4 months, with applications at least twice a day. The contours of the left cheek are shown from a perspective looking up from the chin towards the left side of the head. The photographs were taken with an Antera 3D digital camera system. No image manipulation was performed. In FIG. 5B, the left cheek appears to have a much reduced volume compared to FIG. 5A, resulting in a much smoother contour.

[0097] Example 6

[0098] 6A-6C and 6D-6F show pre- and post-treatment photographic images, respectively, of an individual treated with a topical composition according to the present invention. The topical composition according to the present invention was applied to the right side of the face. The treatment period was 199 days, with applications at least once per day. FIG. 6A and FIG. 6D show pre- and post-treatment photographic images. FIG. 6B and 6E show pre- and post-treatment topographic images of the lower cheek, with the raised areas darker and the areas selected for quantification highlighted. FIG. 6G shows a graph comparing the volume in cubic millimeters of the highlighted areas of the lower cheek shown in FIG. 6B and 6E, as automatically calculated by the Antera system. It can be seen that the treatment reduced the volume of the lower cheek by 14%, significantly improving the appearance of sagging. FIG. 6C and FIG. 6F show pre- and post-treatment topographic images of the cheekbone area, with the raised areas darker and the areas selected for quantification highlighted. Figure 6H is a graph comparing the highlighted volume in cubic millimeters of the lower cheek area shown in Figures 6C and 6F, as automatically calculated by the Antera system. It can be seen that the treatment resulted in a 14% increase in highlighted volume, significantly improving the appearance of cheekbone prominence and contour.

[0099] Example 7

[0100] 7A-7E and 7F-J show pre- and post-treatment photographic images, respectively, of an individual treated with a topical composition according to the present invention. The topical composition according to the present invention was applied to the left side of the face. The treatment period was 199 days, with applications at least once a day. FIG. 7A and FIG. 7F show pre- and post-treatment photographic images. FIG. 7B and 7G show pre- and post-treatment topographic images of the cheekbone area, with the raised areas darker and the areas selected for quantification highlighted. FIG. 7K shows a comparison of the volume of the highlighted areas of the cheekbone area shown in FIG. 7B and 7G in cubic millimeters, as calculated automatically by the Antera system. It can be seen that the treatment resulted in a 10% increase in the volume of the highlighted areas of the cheekbone, significantly improving the prominence and contour of the cheekbone. FIG. 7C and FIG. 7H show pre- and post-treatment topographic images, with the raised areas darker and the areas below the cheek highlighted for quantification. Figure 7L is a graph comparing the volume of the highlighted area in cubic millimeters of the lower cheeks shown in Figures 7C and 7H, as automatically calculated by the Antera system. Treatment reduced the volume of the highlighted area by 11%, significantly improving the appearance of the sagging lower cheeks. Figures 7D and 71 show pre- and post-treatment topographic images of the cheekbones, with the sunken areas darker and the areas selected for quantification highlighted. Figure 7M is a graph comparing the volume of the highlighted area in cubic millimeters of the tear troughs shown in Figures 7D and 7I, as automatically calculated by the Antera system. Treatment increased the volume of the highlighted area by 30%, significantly improving the appearance of the volume defect or periorbital depression. Figures 7E and 7J show pre- and post-treatment topographic images, with the sunken areas darker and the mid-cheek sunken areas highlighted for quantification. Figure 7N shows a comparison of the highlighted volume in cubic millimeters in the mid-cheek hollow, as automatically calculated by the Antera system. The treatment did not change the volume of the highlighted area, indicating that filling was not applied to areas that did not require filling.

[0101] Example 8

[0102] 8A-8C and 8D-8F show pre- and post-treatment photographic images, respectively, of an individual treated with a topical composition according to the present invention. The topical composition according to the present invention was applied to the left side of the face. The treatment period was 105 days, with applications at least once a day. 8A and 8F show pre- and post-treatment photographic images. 8B and 8E show pre- and post-treatment topographic images, with the raised areas darker and the lower cheek area selected for quantification highlighted. 8G shows a graph comparing the volume in cubic millimeters of the highlighted areas of the lower cheek shown in 8B and 8E, as automatically calculated by the Antera system. It can be seen that the treatment reduced the volume of the lower cheek by 18%, significantly improving the appearance of sagging. 8C and 8F show pre- and post-treatment topographic images, with the sunken areas darker and the sunken areas of the mid-cheek highlighted for quantification. Figure 8H is a graph comparing the highlighted volume in cubic millimeters of the mid-cheek hollows shown in Figures 8C and 8F, as automatically calculated by the Antera system. It can be seen that the treatment reduced the highlighted volume by 14%, significantly improving the appearance of the jawline.

[0103] Example 9

[0104] 9A-9C and 9D-8F show pre- and post-treatment photographic images, respectively, of an individual treated with a topical composition according to the present invention. The topical composition according to the present invention was applied to the left side of the face. The treatment period was 125 days, with applications at least once a day. 9A and 9F show pre- and post-treatment photographic images. 9B and 9E show pre- and post-treatment topographic images, with the raised areas darker and the selected lower cheek highlighted for quantification. 9G shows a graph comparing the volume in cubic millimeters of the highlighted upper cheek areas shown in 9B and 9E, as automatically calculated by the Antera system. It can be seen that the treatment increased the volume of the selected upper cheek area by 18%, significantly improving the appearance of sagging and the contour of the upper cheek area. 9C and 9F show pre- and post-treatment topographic images, with the depressed areas darker and the depressed mid-cheek areas highlighted for quantification. Figure 9H is a graph comparing the highlighted volume in cubic millimeters of the mid-cheek hollow shown in Figures 9C and 9F, as automatically calculated by the Antera system. It can be seen that the treatment reduced the highlighted volume by 64%, significantly improving the appearance of the jawline.

[0105] Example 10

[0106] 10A-D and 10E-10H show pre- and post-treatment photographic images, respectively, of an individual treated with a topical composition according to the present invention. The topical composition according to the present invention was applied to the right side of the face. The treatment period was 256 days, and the application was at least once a day. FIG. 10A and FIG. 10E show pre- and post-treatment photographic images. FIG. 10B and FIG. 10F show pre- and post-treatment topographic images, with the raised areas darker and the selected cheekbones highlighted for quantification. FIG. 10I shows a comparison of the volume in cubic millimeters of the highlighted cheekbones shown in FIG. 10B and FIG. 10F, as calculated automatically by the Antera system. It can be seen that the treatment increased the selected cheekbones' volume by 12%, significantly improving the prominence and contour of the cheekbones. FIG. 10C and FIG. 10G show pre- and post-treatment topographic images, with the raised areas darker and the selected upper cheeks highlighted for quantification. FIG. 10J is a graph comparing the volume in cubic millimeters of the highlighted areas of the upper cheeks shown in FIGS. 10C and 10G, as automatically calculated by the Antera system. The treatment increased the volume of the highlighted areas of the upper cheeks by 19%, signifying a significant improvement in the appearance of upper cheek lifting and a reduction in the appearance of sagging. FIGS. 10D and 10H are topographical images of pre-treatment and post-treatment images, with the depressed areas shown darker and the mid-cheek depressed areas highlighted for quantification. FIG. 10K is a graph comparing the volume in cubic millimeters of the highlighted areas of the mid-cheek depressed areas shown in FIGS. 10D and 10H, as automatically calculated by the Antera system. The treatment increased the mid-cheek depressed area by 7% in the selected areas, signifying a significant improvement in the appearance of the jawline.

[0107] Example 11

[0108] 11A-11C and 11D-11F show pre- and post-treatment photographic images, respectively, of an individual treated with a topical composition according to the present invention. The topical composition according to the present invention was applied to the left side of the face, under the eye. The treatment period was 127 days, with applications at least once every two days. FIG. 11A and FIG. 11D show pre- and post-treatment photographic images. FIG. 11B and 11E show pre- and post-treatment topographic images, with the depressed areas shown darker and the areas of the tear trough selected for quantification highlighted. FIG. 11G shows a graph comparing the volume in cubic millimeters of the areas of the tear trough highlighted in FIG. 11B and 11E, as automatically calculated by the Antera system. It can be seen that the treatment increased the volume of the selected areas of the tear trough by 11%, resulting in a significant improvement in the periorbital depression. Figures 11C and 11F show topographical images of pre- and post-treatment images with raised areas appearing darker and highlighting the cheekbone area for quantification. Figure 11H shows a comparison of the volume in cubic millimeters of the highlighted areas of the cheekbone areas of Figures 11C and 11H, as automatically calculated by the Antera system. It can be seen that the treatment increased the volume of the selected cheekbone area by 41%, significantly improving the appearance of the cheekbone area.

Claims

1. A topical composition effective for improving the appearance of skin, comprising at least one adipogenic component, at least one lipolytic agent and at least one penetrating agent, said improvement comprising improving the appearance of volume defects.

2. A topical composition effective for improving the appearance of skin, comprising at least one adipogenic component, at least one lipolytic agent and at least one penetrating agent, said improvement comprising improving the appearance of sagging skin.

3. A topical composition effective for preventing skin damage caused by sunburn, weight gain, weight loss or physical exercise, comprising at least one adipogenic component, at least one lipolytic agent and at least one penetrating agent, wherein the damage to be prevented is associated with a reduction in the number of dermal adipocytes and their hypertrophy.

4. The topical composition of claim 1 , wherein the improvement in the appearance of volume deficiency occurs without causing an increase in the appearance of volume excess.

5. The topical composition of claim 1 , wherein the improvement in the appearance of volume defects occurs concomitantly with an improvement in the appearance of sagging.

6. The topical composition of claim 1 , wherein the improved appearance occurs on the face.

7. The topical composition of claim 1 , wherein the amelioration of the volumetric defect comprises an increase in periorbital volume.

8. The topical composition of claim 1 , wherein the improvement of the volume defect comprises an increase in volume along the cheekbones.

9. The topical composition of claim 1 , wherein the improvement of the volume defect comprises an increase in the volume of the upper cheeks.

10. The topical composition of claim 2 , wherein the improvement in the appearance of sagging skin comprises a reduction in the volume of the lower cheek adjacent the nasolabial fold.

11. The topical composition of claim 2 , wherein the improvement in the appearance of sagging skin comprises increasing the volume of the upper cheek area below the cheekbone.

12. The topical composition of claim 2 , wherein the improvement in the appearance of sagging skin comprises an increase in the volume of the mid-cheek hollow.

13. 2. The topical composition of claim 1, wherein the at least one adipogenic component is selected from the group consisting of naturally occurring unsaturated fatty acids having a carbon chain length of 18 or more.

14. 2. The topical composition of claim 1, wherein the at least one adipogenic component is selected from the group consisting of aculeatine, ascorbic acid, black soybean extract, chlorogenic acid, Cinnamomum cassia extract ...

15. 2. The topical composition of claim 1, wherein the at least one adipogenic component is selected from the group consisting of (2S)-7,4'-dihydroxy-8-prenylflavan, Morus yunnanensis extract, 3-butylhydroxyanisole, 4-methoxychalcone, Anemone annua extract, Artemisia santolinifolia extract, Artemisia oleracea, Babakin, Sugarcane extract, Melastomataceum extract, Piper chabai fruit extract, Phloretin, Hollandaea fruit extract, Sage extract, Sakuranetin, Sarsapogenin, Tenyokenkoushi extract, and Vanadium.

16. The at least one adipogenic component is selected from the group consisting of 10-oxo-12(Z)-octadecenoic acid, 13-oxo-9(Z),11(E),15(Z)-octadecatrienoic acid, 15-(S)-hydroxyeicosatetraenoic acid, acrylamide, Bidens genus extract, Brazilian red propolis extract, butylated hydroxyanisole, chebulazic acid, Chlorella vulgaris extract, Silybum membranaceum extract, cyanidin-3-glucoside, daidzein, diallyl disulfide, Echinacea purpurea root extract, emodin, flavanones, furan fatty acid 9M5, geranylgeraniol, ginsenoside 20S-protopanaxatriol, ginsenoside Rbl, ginsenoside Re, ginsenoside Rh2, glabridin, Heracleum dissectum Lebb Extract, Hydrogen Sulfide, Illicium Verum Extract, Obliquus Obliquus Extract, Isoimperatorin, Lactic Acid, Lecithin, Licorice Extract, Loquat Extract, Moringa Concanensis Nimmo Extract, N-Oleyl Glycine, N. nouchali Seed Extract, Norwogonin, Notopterygium incisum Root Extract, Palmitoyl Lactate, Pentamethylquercetin, Phenyl Lactate, Quinine, Retrofractamide A, Rheum palmatum Extract, 2. The topical composition of claim 1, wherein the active ingredient is selected from the group consisting of: Scutellaria Baicalensis L) rhizome, S-adenosylmethionine, Sangenol F, Scutellaria Baicalensis extract, soybean pinitol, spermidine, tectochrysin, myrobalan fruit extract, Tetracera indica merr. extract, tetramethylkaempferol, umbelliferone, wakame extract, vitamin B3, and vitamin B6.

17. 2. The topical composition of claim 1, wherein the at least one lipolytic component is selected from the group consisting of ascorbic acid, butyrate, chrysanthemum extract, chlorogenic acid, bitter orange extract, eicosapentaenoic acid, gallic acid, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, INDUS 810, black ginger extract, lycopene, magnolol, magnolia bark extract, Japanese mulberry extract, pueraria lobata root extract, resveratrol, Schisandra chinensis extract, sodium butyrate, Solenostemma argel extract, Mizurembu extract, T. foenum graecum seed extract, triphenyl phosphate, and tyramine.

18. 18. The topical composition of claim 17, wherein the at least one lipolytic agent is black ginger extract.

19. The at least one lipolytic component is selected from the group consisting of 3-iodothyronamine, bael tree leaf extract, Anoectochilus formosanus extract, arginine, bitter melon extract, brucein A, brucein B, brucein C, 3'-hydroxybrucein A, brusatol, bruceanthinol, scutellaria baicalensis seed extract, Centella asiatica leaf extract, cane extract, Cyclopia maculata extract, fermented castanea extract, and the like. crenata inner shell extract, forskolin, Sanshin extract, genipin, Hemerocallis fulva extract, Manchuria walnut extract, Licarin A, Lychee fruit extract, magnesium, malic acid, okadaic acid, Paecilomyces hepiali mycelium extract, palmitoleic acid, Phaseolus vulgaris extract, Posidonia oceanica (L.) delile extract, Salacia (S.) 2. The topical composition of claim 1, wherein the active ingredient is selected from the group consisting of: Acanthus reticulata Extract, Sea Cucumber Saponin Echinosid A, Sarmientobar Bark Leaf Extract, Soy Hydrolysate, Soyasapogenol A, Soyasapogenol B, Octopamine, N-Methyltyramine, Myrtle Beach, TAT-Glycine-Lysine-Histidine Complex, Terminalia Sericea Extract, Chan Chin Extract, and Zanthoxylum Indicum Seed Oil.

20. The at least one lipolytic component is selected from the group consisting of acetyl-keto-β-boswellic acid, aged black garlic extract, almond skin extract, andiroba extract, apigenin, apple extract, Artemisia anguicida extract, Astilbe chinensis Franc. et Savet. extract, white birch bark, B. Platyphylloside, berberine, bergamottin, betulinic acid, bilobalide, black bean extract, black tea extract, Brassica campestris spp. rapa root extract, caffeine, capsanthin, capsicum seed oil, capsaicin, carnitine, chitosan, chrysophanol, cinnamaldehyde, sirsimarin, Korean thistle (Cirsium setidens nakai) extract, bergamot extract, satsuma mandarin extract, clove extract, coffee extract, Commiphora mukul, crocin, Japanese pumpkin extract, turmeric extract, honeybush (Cyclopia intermedia), epigallocatechin gallate, euglena, eurycomanone, Nagaekasa extract, fucoidan, fucoxanthin, bladderwrack (Fucus vesiculosus) extract, Garcinia (Garcinia gummi-gutta) extract, Agarwood extract, genistein, germinated soy protein hydrolysate, ginkgo biloba extract, ginsenoside Rgl, gomisin, grape seed extract, grape skin extract, green tea extract, Kanamgura, hydroxytyrosol, hydroxysafflor yellow A, isopropylnorsinephylline, kaempferol, Korean Chungtaejeon tea extract, lipoic acid, lotus leaf extract, lotus seed extract, luteolin, spiritual herb (Lysimachia foenum-graecum) extract Moringa Seed Extract, Morusin, Banana Pulp Extract, Myricanol, Naringenin-7-O-Glucoside, New Zealand Blackcurrant Extract, Oleanolic Acid, Oleoresin Capsicum, 2. The topical composition of claim 1, wherein the active ingredient is selected from oleuropein, P-synephrine, pear pomace extract, plum extract, buckwheat, pterostilbene, pycnogenol, quercetin, quinic acid, raspberry ketone, rubus fruticosus extract, purple yam extract, rutin, chinese anemone extract, sericoside, sinensetin, spilanthol, stem bromelain extract, ginseng extract, synephrine, syringic acid, tanshinone IIA, dandelion extract, triamcinolone acetonide, ursolic acid, vitamin D, widrol, xansigen, and xanthohumol.

21. 10. The topical composition of claim 1, wherein the at least one penetrating agent is selected from the group consisting of urea, imidourea, palmitate, isopropyl palmitate, isopropyl myristate, propylene glycol, and non-ionic detergents.

22. 14. The topical composition of claim 13, wherein the naturally occurring unsaturated fatty acid having a carbon chain length of 18 or more is present in the composition at about 5% (w / w) to about 40% (w / w).

23. The topical composition of claim 1 , wherein the penetrating agent is present in the composition in a proportion of about 5% (w / w) to about 25% (w / w).

24. 2. The topical composition of claim 1, wherein the weight percentage of the adipogenic component present in the composition is greater than the weight percentage of the lipolytic agent present in the composition.

25. The topical composition of claim 1 further comprising an agent having indirect adipogenic activity.

26. The topical composition of claim 1 further comprising an agent having indirect lipolytic activity.

27. Optionally, a topical composition effective for increasing or decreasing subcutaneous fat volume, said composition comprising at least one adipogenic component, at least one lipolytic agent, and at least one penetrating agent.

28. A method for improving the appearance of an individual's skin, comprising topically applying to the skin a composition comprising at least one lipolytic agent having lipolytic activity, at least one adipogenic component having adipogenic activity, and at least one penetrating agent.

29. 29. The method of claim 28, wherein the composition is applied to overlapping areas of a keratin-based skin surface.

30. 30. The method of claim 28, wherein the composition is applied to parts of the body exposed to the sun.

31. The method of claim 29 , wherein the composition is applied to the face.

32. 29. The method of claim 28, wherein the lipolytic agent having lipolytic activity is included in a composition separate from a composition comprising an adipogenic component having adipogenic activity.

33. 33. The method of claim 32, wherein the topical application of the two separate compositions is performed in close temporal proximity or as part of a coordinated regimen.

34. 34. The method of claim 33, wherein after application of the composition to the periorbital, malar and upper cheek areas of the face, there is a visible reduction in the appearance of hollows.

35. 35. The method of claim 34, wherein there is a visible reduction in the appearance of sagging skin or a visible improvement in the definition of the cheekbones, periorbital areas, upper cheeks, lower cheeks, or jawline.

36. 36. The method of claim 35, wherein the improvement in skin appearance is necessitated in part by sun exposure, weight gain, weight loss, or physical exercise.

37. 29. The method of claim 28, wherein the combination of agents having lipolytic and adipogenic activity is contained in a single composition.

38. A method for treating or preventing defects in the appearance of the skin using a combination of an adipogenic component and a lipolytic agent.

39. 39. The method of claim 38, wherein such treatment or prevention involves the use of two or more compositions separately comprising a lipolytic agent and an adipogenic component, and wherein the compositions comprising the lipolytic agent and the adipogenic component may be applied to the same area of ​​skin.

40. A method for increasing the appearance of volume in areas of the skin of an individual in need thereof, and for reducing the appearance of volume in areas of the skin of the same individual in need thereof, comprising topically applying to the skin area of ​​the individual a composition comprising an adipogenic component, a lipolytic agent and at least one penetrating agent.

41. A method for increasing the appearance of volume in areas of the skin where an individual needs it, without increasing the appearance of volume in areas of the skin where the same individual does not need it, comprising topically applying to the area of ​​the skin of the individual a composition comprising an adipogenic component, a lipolytic agent and at least one penetrating agent.

42. A method for reducing the appearance of volume in areas of the skin where an individual needs it, without reducing the appearance of volume in areas of the skin where the same individual does not need it, comprising topically applying to the area of ​​the skin of the individual a composition comprising an adipogenic component, a lipolytic agent and at least one penetrating agent.

43. A method for increasing the volume of adipose tissue in an area of ​​the skin of an individual in need thereof, and for reducing the volume of adipose tissue in an area of ​​the skin of the same individual in need thereof, comprising topically applying to the area of ​​the skin of the individual a composition comprising an adipogenic component, a lipolytic agent and at least one penetrating agent.

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