Methods and formulations for stimulating skin stem cells, reducing wrinkles and reversing the characteristics of aging

Abstract

There is a need for formulations to reduce wrinkles and sagging skin, and to improve skin quality in general. A novel formulation of kaempferol is provided which stimulates skin stem cells in humans. A topical composition is proviced for enhancing the proliferation of skin stem cells, the composition comprising kaempferol, hyaluronic acid plus optionally sodium hyaluronate, and Moringa extract.

Description

[0001] Methods and formulations for stimulating skin stem cells, reducing wrinkles and reversing the characteristics of aging

[0002] FIELD OF INVENTION

[0003] This invention relates to the use novel formulations of kaempferol to stimulate skin stem cells in humans to reduce wrinkles and sagging skin and improve skin quality.

[0004] BACKGROUND

[0005] Molecules which enhance the activity and function of stem cells such as skin-derived precursors (SKPs) are desirable as they promote their proliferation, self-renewal, and ability to produce cells to repair and regenerate tissues. SKPs are dermal stem cells that are required for the maintenance and repair of the skin (Toma et al, 2001 , Biernaskie et al, 2009) that when depleted in mice results in premature aging of the skin, ulcerations and blisters (Su et al, 2009). Molecules that stimulate SKPs proliferation accelerate skin repair in a mouse model of wound healing (Naska et al, 2016). Age-related dermal thinning is associated with an increase in wrinkles, skin fragility heightening the risk of trauma to the skin, delayed wound healing, increased risk of infection, dry skin, impaired thermal regulation, decreased vitamin D synthesis and loss of skin integrity. Molecules that stimulate SKPs may be therefore be highly advantageous for cosmetic formulations and methods (e.g., hair growth and skin regeneration) and therefore new combinations and dosage forms and formulations that allow for the efficient and effective delivery of such molecules are desirable. For additional information on SKPs see Toma, JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat. Cell Biol. 2001; 3(9):778-784; and Biernaskie J, Paris M, Morozova O, Fagan BM, Marra M et al. SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells. Cell Stem Cell 2009; 5(6):610-623. Kaempferol is a stem cell proliferation activator as discovered using drug screening for proliferation enhancers of human SKPs (Naska S, Yuzwa SA, Johnston APW, Paul S, Smith KM et al. Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair. Stem Cell Reports 2016; 6:74-84).Kaempferol is a natural flavonoid found in many edible plants that has low toxicity and wide safety margins.

[0006] US patent no. 8,748,177 entitled “Compositions for proliferation of cells and related methods” discloses methods and compounds useful for increasing the proliferation of skin-derived precursors (SKPs) and is incorporated by references in its entirety along with its related applications No.

[0007] PCT / US2009 / 058723, filed on Sep. 29, 2009; provisional application no. 61 / 101443, filed on Sep.30, 2008, provisional application no. 61 / 367,780, filed on Jul. 26, 2010, provisional application no. 61 / 426,160, filed on Dec.

[0008] 22, 2010.

[0009] Canadian patent no. 2,738,496, which claims priority to provisional application no. 61 / 101443, claims the use of SKP cell proliferation agent alprostadil for hair growth.

[0010] Preeti, et al. “Kaempferol: Topical Applications and Nanoformulations in the Treatment of Diseases” in Current Bioactive Compounds, 2023, 19, e18042321 6003. DOI: 10.2174 / 157340721966623041 8121102 reviews various studies on the uses of kaempferol.

[0011] As used herein an “effective amount” means an amount of a physiologically active compound or composition sufficient to induce a positive modification in the condition to be regulated or treated, (e.g., hair growth, wrinkle reducing or wound healing) but low enough to avoid serious side effects. A safe and effective amount of the compound or composition will vary with the particular condition being treated, the age and physical condition of the end user, the severity of the condition being treated / prevented, the duration of the treatment, the nature of other treatments, the specific compound or product / composition employed, the particular cosmetically-acceptable carrier utilized, and like factors.

[0012] In spite of the existing knowledge on kaempferol as a dietary supplement, there remains a need for effective, low dose, topical formulations and methods of use of SKPs cell proliferation enhancers such as kaempferol for cosmetics. High doses of such molecules can have unwanted effects such as skin coloration.

[0013] FIGURES

[0014] Figure 1 shows the pooled results from the experiment of Example 1.DETAILED DESCRIPTION OF THE INVENTION

[0015] In a first aspect described herein, there are provided compositions and methods for promoting skin health or even skin repair. In one embodiment the methods include administering to a subject in need thereof a composition including an effective amount of kaempferol or a pharmaceutically acceptable salt or active metabolite thereof.

[0016] In certain non-limiting embodiments, the composition can be administered one or more times a day. In some non-limiting embodiments, the composition is administered for at least seven to twenty eight days. In other non-limiting embodiments, the composition is administered for more than twenty eight days. In certain non-limiting embodiments, the composition can increase SKPs proliferation and / or SKPs activity.

[0017] Kaempferol is a flavonoid compound found in various plants, known for its potent antioxidant, anti-inflammatory, and skin-soothing properties. In the instant invention kaempferol is included in specific dosages in order to increase SKPs proliferation.

[0018] Kaempferol (Kaempferol-3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) kaempferol flavonol and tetrahydroxyflavone exists in many forms, including Kaempferol glycosides and Kaempferol derivatives. All of these various forms of kaempferol are used herein synonymously with the term “kaempferol”.

[0019] Kaempferol glycosides include astragalin (kaempferol-3-O-glucoside), populnin (kaempferol-7-O-glucoside), nicotiflorin (K-3-rh), and kaempferitrin (kaempferol-3,7-dirhamnoside).

[0020] Kaempferol derivatives include kaempferol-3-O-avruyl-diglucoside-7-O-glucoside, kaempferol-3-O-cafeyl-diglucoside-7-O-glucoside, kaempferol-3-O-coumaryl-diglucoside-7-O-glucoside, and kaempferol-3-O-p-coumaryl-diglucoside-7-O-glucoside.

[0021] Naska et al. showed that 1 uM of kaempferol was the most effective using SKPs from human foreskin. That work showed that even 100 nM was effective on SKPs cultured from 5 of 9 people. 0.5% (5mg / ml) topically applied to humans was calculated to deliver the equivalent to a 1 uM concentration on cultured human SKPs.Certain embodiments of the instant invention provide a combination of the SKP proliferation agent kaempferol with the powerful humectant (a substance that draws water into the skin, hair, or nails) and moisturizing agent hyaluronic acid together with antioxidants to repair and enhance damaged or aging skin.

[0022] Hyaluronic Acid is a powerful humectant and moisturizing agent used in cosmetic products for its ability to attract and retain water in the skin. This naturally occurring glycosaminoglycan is known for its exceptional ability to hold up to 1,000 times its weight in water, providing intense hydration and plumping effects to the skin. In cosmetic formulations, hyaluronic acid helps to improve skin elasticity, smoothness, and overall texture by deeply hydrating the epidermis. It also supports the skin’s natural barrier function, preventing moisture loss and maintaining a youthful, radiant complexion. In certain embodiments of the instant invention Moringa extract is included. In certain embodiments, Moringa extract is derived from the seeds of the Moringa tree, known for its high concentration of antioxidants, vitamins, and essential fatty acids. In cosmetic applications, this extract serves as an antioxidant, protecting the skin from environmental pollutants and oxidative damage. Moringa Oleifera seed extract has powerful anti-inflammatory properties, helping to calm and soothe irritated skin. Additionally, it is known for its detoxifying effects, as it can help to purify and cleanse the skin by removing toxins and impurities. This extract also nourishes the skin, supporting moisture retention and enhancing skin elasticity, making it beneficial for anti-aging, brightening, and hydration formulations. Its ability to act as a natural emollient helps to maintain smooth, soft skin and improve overall skin health.

[0023] Honokiol is a bioactive compound derived from the bark of the Magnolia tree. It functions primarily as an antioxidant in cosmetic formulations, helping to neutralize free radicals and protect the skin from oxidative stress. Magnolol, another active component found in Magnolia bark, is a potent antioxidant and anti-inflammatory agent. In cosmetic applications, Magnolol is used to protect the skin from oxidative damage, which is a major factor in skin aging. It helps in reducing the formation of free radicals and improves skin resilience. Additionally, it may contribute to reducing inflammation,thus supporting skin health and reducing the appearance of redness and irritation, while also enhancing the overall stability of cosmetic formulations. Tocopherol (Vitamin E) is a potent antioxidant commonly used to protect the skin from oxidative damage caused by free radicals. It helps to neutralize reactive oxygen species (ROS), which can contribute to premature skin aging, inflammation, and damage to skin cells. In addition to its antioxidant properties, Tocopherol also acts as a skin-conditioning agent, promoting moisture retention and enhancing the skin's natural barrier function. Tocopherol supports skin hydration and provides soothing effects, making it a valuable ingredient in anti-aging, moisturizing, and protective skincare formulations. Furthermore, it enhances the stability of formulations by preventing the degradation of other sensitive ingredients, improving the overall shelf-life of cosmetic products.

[0024] Vaccinium Macrocarpon (Cranberry) Fruit Extract is a rich source of antioxidants, particularly vitamin C and flavonoids, that is widely used in cosmetics for its astringent, anti-inflammatory, and skin-brightening properties. As an astringent, it helps to tighten and tone the skin, reducing the appearance of pores and promoting a smoother, more even complexion. Cranberry extract also has natural antimicrobial properties, which can help to prevent acne and other skin blemishes by reducing bacteria on the skin’s surface. Additionally, the high concentration of antioxidants in Cranberry Extract helps to protect the skin from oxidative stress and free radical damage, making it a valuable ingredient in antiaging and protective skincare formulations. Its soothing effects also help to reduce redness and inflammation, making it suitable for sensitive or irritated skin.

[0025] In certain embodiments of the instant invention emollients, emulsifiers, stabilizing agents, surfactants, skin conditioning agents, surfactants, solvents, smoothing agents, cleansing agents and perfuming agents are included.

[0026] In certain embodiments the emollients are selected from c12-16 alcohols, oleic / linoleic / linolenic polyglycerides, palmitic acid, glyceryl caprylate, glyceryl stearate, apricot kernel oil, polyglyceryl-6 esters, squalane, coco-caprylate / caprate, dicaprylyl carbonate, octyldodecanol, and caprylyl glycol.In certain embodiments the emulsifiers are selected from c12-16 alcohols, oleic / linoleic / linolenic polyglycerides, sodium stearoyl glutamate, palmitic acid, glyceryl caprylate, glyceryl stearate, apricot kernel oil, polyglyceryl-6 esters, polyglyceryl-6 oleate, hydrogenated lecithin, c12-20 alkyl glucoside, carbomer, xanthan gum, sorbitan palmitate, and maltodextrin.

[0027] In certain embodiments the stabilizing agents are selected from c12-24 alcohols, oleic / linoleic / linolenic polyglycerides.

[0028] In certain embodiments the surfactant are selected from oleic / linoleic / linolenic polyglycerides, apricot kernel oil polyglyceryl-6 esters, and c12-20 alkyl glucoside.

[0029] In certain embodiments the cleansing agents are selected from sodium stearoyl glutamate.

[0030] In certain embodiments the skin conditioning agents are selected from sodium stearoyl glutamate, apricot kernel oil polyglyceryl-6 esters, squalane, coco-caprylate / caprate, dicaprylyl carbonate, octyldodecanol, hydrogenated lecithin, lauroyl lysine, polyglyceryl-10 oleate, ectoin, pentylene glycol, triheptanoin, butyrospermum parkii (shea) butter, polyglutamic acid, maltodextrin, honokiol, and caprylyl glycol.

[0031] In certain embodiments perfuming or masking agents are included and are selected from glycerin and octyldodecanol.

[0032] In certain embodiments the viscosity controlling / gel forming agents are selected from c12-16 alcohols, oleic / linoleic / linolenic polyglycerides, carbomer, lauroyl lysine, xanthan gum, stearalkonium, hectorite, and propylene carbonate.

[0033] In certain embodiments the film forming agents are selected from dilinoleic acid / butanediol copolymer and castor oil / ipdi copolymer.

[0034] In certain embodiments the smoothing agent is niacinamide which also has positive benefits for the skin.

[0035] In certain embodiments the solvents are selected from water, propanediol, propylene carbonate, 1,2-hexanediol, and glycerin.Preservatives such as sodium benzoate may be included in certain embodiments of the instant invention.

[0036] Emollients are ingredients in cosmetic and skincare products that helps to soften, smooth, and moisturize the skin. Emollients work by forming a protective layer on the skin’s surface, which helps to lock in moisture and prevent water loss. This barrier also helps to restore the skin's natural hydration levels, making it feel smoother and more supple.

[0037] Emollients can be found in a variety of cosmetic formulations, including moisturizers, creams, lotions, balms, and oils. They are particularly beneficial for dry, flaky, or irritated skin, as they help to reduce roughness and enhance the skin's elasticity. Emollients are often derived from natural oils, fatty acids, or plant-based sources, but they can also be synthetic. Emollients are essential for maintaining healthy skin by providing hydration, improving texture, and protecting the skin from environmental factors that can lead to dryness and irritation.

[0038] C12-16 Alcohols are a blend of fatty alcohols derived from natural oils and fats. They function as emollients in cosmetic formulations by providing a smooth, silky texture and enhancing the skin's softness. These alcohols help to improve the spreadability of products while offering moisturizing benefits by forming a thin barrier on the skin’s surface that helps prevent moisture loss. Additionally, C12-16 Alcohols can stabilize emulsions and enhance the consistency of the final product, making them a versatile ingredient in skincare and haircare formulations.

[0039] Oleic, Linoleic, and Linolenic Polyglycerides are naturally derived fatty acid derivatives that serve as emollients in cosmetic products. These compounds are known for their ability to penetrate the skin and provide deep hydration, leaving the skin feeling soft and nourished without being greasy. Their unique structure also helps to repair the skin’s lipid barrier, improving moisture retention and preventing dehydration. These emollients are particularly beneficial for sensitive or dry skin, as they can enhance skin elasticity and provide long-lasting comfort.

[0040] Palmitic Acid is a saturated fatty acid commonly used as an emollient in cosmetic formulations. It helps to create a smooth, soft texture on the skin by forming a protective barrier that reduces water loss. This ingredient contributes to the overall stability of emulsions and improves thespreadability of creams and lotions. Additionally, Palmitic Acid helps to maintain the skin's natural moisture balance, leaving it feeling hydrated, soft, and smooth.

[0041] Glyceryl Caprylate is a natural emulsifier and emollient derived from plantbased sources, known for its mildness and skin-conditioning properties. It helps to enhance the skin’s barrier function, providing hydration while improving the texture and spreadability of formulations. Glyceryl Caprylate also exhibits antimicrobial properties, helping to stabilize formulations and prevent the growth of microorganisms, thereby extending product shelf life. Glyceryl Stearate is a fatty acid ester of glycerin and stearic acid, commonly used as an emollient, emulsifier, and stabilizer in skincare products. It acts as a skin-conditioning agent by forming a protective barrier that prevents moisture loss, leaving the skin feeling soft and smooth.

[0042] Glyceryl Stearate also helps to blend oil and water-based ingredients, stabilizing emulsions and enhancing the overall texture of creams, lotions, and other cosmetic formulations.

[0043] Apricot Kernel Oil Polyglycerol-6 Esters are plant-derived emollients that provide a light, non-greasy feel to formulations while enhancing the skin’s hydration. These esters function as emulsifiers and skin-conditioning agents, helping to improve skin elasticity and moisture retention. Their gentle nature makes them suitable for sensitive skin, and they help deliver essential fatty acids, vitamins, and antioxidants to nourish and protect the skin.

[0044] Squalane is a highly effective emollient and moisturizer derived from plant or shark sources. It mimics the skin’s natural sebum, providing deep hydration without leaving a greasy residue. Squalane helps to restore the skin’s moisture balance, enhance its elasticity, and improve the appearance of fine lines and wrinkles. As a stable and non-comedogenic ingredient, it is well-suited for all skin types, including oily and acne-prone skin.

[0045] Coco-Caprylate / Caprate is a plant-derived ester of coconut oil used as a lightweight emollient in cosmetic formulations. It provides a silky, smooth feel and enhances the spreadability of products without leaving a greasy residue. This ingredient also helps to moisturize and soften the skin,making it ideal for dry or sensitive skin types. Its non-irritating properties make it suitable for use in a variety of skincare applications.

[0046] Dicaprylyl Carbonate is a mild emollient derived from caprylic acid, offering skin-conditioning benefits without causing irritation. It helps to improve the texture of cosmetic formulations, providing a silky, non-oily feel while enhancing skin softness and hydration. This ingredient also acts as a stabilizer for emulsions, promoting the uniform distribution of oil and water phases in creams and lotions.

[0047] Octyldodecanol is a fatty alcohol used as an emollient and skinconditioning agent in cosmetic products. It is prized for its ability to enhance the spreadability and texture of formulations, leaving a smooth, non-greasy finish on the skin. Octyldodecanol also helps to create a protective barrier that retains moisture, making it particularly beneficial for dry or dehydrated skin.

[0048] Caprylyl Glycol is a multi-functional ingredient that acts as both a skinconditioning agent and a preservative booster in cosmetic formulations. It helps to maintain skin hydration by preventing water loss and improving the skin's moisture balance. Additionally, Caprylyl Glycol enhances the texture of formulations, providing a soft, smooth finish while supporting the overall stability and shelf life of the product.

[0049] Emulsifiers are ingredients used in cosmetic and personal care formulations to stabilize and blend two or more immiscible substances. These substances naturally don’t mix — for example, oil and water tend to separate when combined — but emulsifiers help to create a uniform and stable mixture, called an emulsion. Without emulsifiers, many skincare products like creams, lotions, and moisturizers would separate into layers, with the oil and water components separating over time.

[0050] Emulsifiers are critical ingredients in the creation of stable, effective, and aesthetically pleasing cosmetic products that combine both water and oil phases. They ensure that the formulation remains consistent, easy to apply, and able to deliver active ingredients effectively to the skin.

[0051] 012-16 Alcohols are fatty alcohols derived from natural sources, commonly used as emulsifiers in cosmetic formulations. They help to stabilize emulsions by reducing the surface tension between water and oil phases,enabling the creation of smooth, homogenous creams, lotions, and other emulsions. In addition to their emulsifying function, they also serve as mild emollients, improving the product's spreadability and texture on the skin. Oleic, Linoleic, and Linolenic Polyglycerides are a blend of polyunsaturated fatty acids that act as emulsifiers and skin-conditioning agents. They improve the stability and texture of emulsions by reducing surface tension between the oil and water phases. Additionally, these polyglycerides enhance skin hydration and help to restore the skin's lipid barrier, promoting healthy, smooth skin. Their ability to penetrate the skin makes them highly effective in moisturizing formulations.

[0052] Sodium Stearoyl Glutamate is a mild, plant-derived surfactant and emulsifier that helps to stabilize emulsions by promoting the uniform dispersion of oil and water phases. It also serves as a skin-conditioning agent, offering gentle hydration and improving the overall texture of cosmetic products. This ingredient is ideal for use in formulations for sensitive skin, as it is non-irritating and biodegradable.

[0053] Palmitic Acid, a saturated fatty acid, is commonly used in cosmetic formulations as an emulsifier and stabilizer. It helps to form and stabilize emulsions by reducing the interfacial tension between water and oil phases. Additionally, it contributes to the overall texture and spreadability of creams, lotions, and other emulsified products, providing a smooth, non-greasy finish while aiding in moisture retention.

[0054] Glyceryl Caprylate is a multi-functional ingredient that serves as both an emulsifier and a skin-conditioning agent. It helps to stabilize emulsions by acting as a co-emulsifier, ensuring a consistent and smooth texture.

[0055] Glyceryl Caprylate also improves skin hydration by preventing moisture loss and creating a barrier that locks in moisture, making it particularly beneficial in formulations designed for dry or sensitive skin.

[0056] Glyceryl Stearate is a widely used emulsifier in cosmetics, acting as both a stabilizer and a skin-conditioning agent. It helps to blend oil and waterbased ingredients, creating smooth, uniform emulsions. It also imparts a soft, velvety feel to the skin and helps prevent moisture loss by forming a protective barrier on the skin’s surface. Glyceryl Stearate is a versatile ingredient, often used in creams, lotions, and other emulsified products.Apricot Kernel Oil Polyglycerol-6 Esters function as emulsifiers in cosmetic formulations, helping to stabilize oil-in-water emulsions. They improve the texture and feel of products by enhancing their spreadability and providing moisturizing benefits. These esters also contribute to the overall nourishment of the skin, providing essential fatty acids and antioxidants that support skin health and hydration.

[0057] Polyglyceryl-6 Oleate is a mild emulsifier that helps stabilize emulsions, enabling smooth texture and consistency. It also enhances the skinconditioning properties of cosmetic formulations, promoting hydration and softness. Its gentle, non-irritating nature makes it suitable for sensitive skin and formulations targeting dry or compromised skin barriers.

[0058] Hydrogenated Lecithin is a phospholipid that serves as an emulsifier and skin-conditioning agent. It is widely used in cosmetic formulations for its ability to stabilize emulsions, improve skin barrier function, and promote moisture retention. This ingredient helps maintain the integrity of the skin, leaving it feeling hydrated, smooth, and protected against environmental stressors.

[0059] C12-20 Alkyl Glucoside is a mild, non-ionic surfactant and emulsifier derived from natural sources such as corn or coconut. It helps to stabilize emulsions by reducing the surface tension between oil and water, ensuring smooth, homogeneous formulations. This ingredient also provides gentle cleansing properties, making it suitable for sensitive skin and formulations that require both emulsification and mild cleansing action.

[0060] Carbomer is a synthetic polymer used in cosmetic formulations to control viscosity and stabilize emulsions. It acts as a thickening agent, allowing for the creation of smooth gels, creams, and lotions. Carbomer improves the texture of formulations, giving them a pleasant feel while also contributing to their overall stability by preventing phase separation.

[0061] Xanthan Gum is a natural polysaccharide used as a thickening agent and stabilizer in emulsions. It enhances the texture of cosmetic formulations, providing a gel-like consistency and preventing phase separation. Xanthan Gum also helps improve the spreadability and stability of creams, lotions, and other emulsified products.Sorbitan Palmitate is a fatty acid ester of sorbitol, used primarily as an emulsifier and stabilizer in cosmetic formulations. It helps to blend oil and water phases, ensuring a smooth, homogeneous texture in emulsified products. Sorbitan Palmitate also contributes to the moisturization of the skin by forming a protective layer that helps prevent moisture loss.

[0062] Maltodextrin is a carbohydrate derived from starch, used in cosmetics as a stabilizing agent and emulsifier. It helps improve the texture and consistency of formulations, contributing to a smooth and even application. Maltodextrin also acts as a humectant, attracting moisture to the skin and promoting hydration.

[0063] Oleic, Linoleic, and Linolenic Polyglycerides function as stabilizing agents in cosmetic formulations by promoting the formation of stable emulsions. These polyglycerides reduce the surface tension between oil and water phases, ensuring consistency and preventing phase separation. They also enhance the skin-conditioning properties of products by providing essential fatty acids that support the skin’s barrier function.

[0064] Oleic, Linoleic, and Linolenic Polyglycerides are a blend of polyunsaturated fatty acids used as surfactants in cosmetic formulations. These ingredients function by reducing the surface tension between oils and water, allowing for the formation of stable emulsions. As surfactants, they help to cleanse the skin by facilitating the removal of dirt, oil, and impurities. Additionally, they help improve skin hydration due to their fatty acid content, making them suitable for sensitive skin while also contributing to the overall stability and texture of emulsions.

[0065] Apricot Kernel Oil Polyglyceryl-6 Esters serve as mild, non-ionic surfactants in cosmetic products. These ingredients help emulsify oil and water phases in formulations, ensuring the smooth, uniform dispersion of ingredients. As surfactants, they aid in cleansing by gently removing oils and impurities from the skin without causing irritation. Furthermore, they provide skinconditioning benefits, helping to nourish and hydrate the skin while enhancing the sensory properties of the product.

[0066] C12-20 Alkyl Glucoside is a mild, plant-derived non-ionic surfactant used in cosmetic formulations for cleansing purposes. This ingredient works by reducing the surface tension between water and oils, allowing for effective cleansing and the formation of stable emulsions. C12-20 Alkyl Glucoside isgentle on the skin, making it suitable for sensitive skin types, and is commonly used in formulations such as shampoos, body washes, and facial cleansers. It also has mild foaming properties and helps maintain skin hydration by preventing excessive moisture loss during cleansing.

[0067] Sodium Stearoyl Glutamate is a naturally derived surfactant and cleansing agent commonly used in cosmetic formulations. It functions by helping to remove dirt, oil, and impurities from the skin without causing irritation or stripping natural oils. As a mild cleanser, it is particularly beneficial for sensitive skin, as it effectively reduces surface tension and enhances the ability of water to wash away contaminants. Additionally, Sodium Stearoyl Glutamate is an emulsifier, which allows it to blend oil and water components, further enhancing the stability of cosmetic formulations and their cleansing efficiency.

[0068] In addition to its function as a cleansing agent, Sodium Stearoyl Glutamate also acts as a skin-conditioning agent. It helps to maintain the skin’s natural moisture balance by forming a protective layer on the skin's surface, preventing excessive water loss. This mild ingredient is gentle and nonirritating, making it suitable for formulations targeting sensitive or dry skin. Its ability to enhance the texture and spreadability of products makes it an important component in moisturizing creams, lotions, and cleansers.

[0069] Apricot Kernel Oil Polyglyceryl-6 Esters also serve as effective skinconditioning agents due to the nourishing properties of apricot kernel oil. Rich in essential fatty acids and antioxidants, this ingredient helps to hydrate and soften the skin. It supports the skin’s natural barrier function, ensuring that moisture is locked in, and helps improve the overall appearance and feel of the skin. These esters are especially beneficial for dry or sensitive skin, providing long-lasting comfort and hydration without causing irritation.

[0070] Squalane is a highly effective skin-conditioning agent known for its deep moisturizing and emollient properties. It closely mimics the skin's natural sebum, providing hydration without clogging pores. Squalane enhances the skin's elasticity, helping to reduce the appearance of fine lines and wrinkles. It supports the skin's barrier function, preventing moisture loss and promoting a smooth, soft texture. Additionally, squalane has antioxidant properties, helping to protect the skin from environmentalstressors, making it suitable for all skin types, including oily and acne-prone skin.

[0071] Coco-Caprylate / Caprate is a mild, non-greasy emollient derived from coconut oil, used for its skin-conditioning properties. It helps to moisturize the skin by forming a protective layer that reduces water loss, leaving the skin feeling soft and smooth. This ingredient also enhances the spreadability of formulations, improving the texture and sensory feel of creams, lotions, and oils. Due to its mild and non-irritating nature, it is suitable for sensitive skin and often used in body care products aimed at hydrating and soothing the skin.

[0072] Dicaprylyl Carbonate is a lightweight, non-oily emollient and skinconditioning agent used in cosmetic formulations. It helps to improve the texture of products, providing a smooth, silky feel on the skin. This ingredient also enhances skin hydration by creating a barrier that locks in moisture while allowing the skin to breathe. Dicaprylyl Carbonate is often used in moisturizers, sunscreens, and anti-aging products for its ability to condition the skin and support the overall feel and performance of the formulation.

[0073] Octyldodecanol is a fatty alcohol used primarily as a skin-conditioning agent in cosmetic products. It has emollient properties that help to soften and smooth the skin, improving its texture and appearance. Octyldodecanol also acts as a solubilizer and stabilizer in formulations, enhancing the delivery and dispersion of active ingredients. Its moisturizing effects are especially beneficial for dry or dehydrated skin, and it is commonly included in creams, lotions, and serums to improve the overall sensory experience of the product.

[0074] Hydrogenated Lecithin is a phospholipid that acts as both an emulsifier and a skin-conditioning agent. It helps to improve the texture and spreadability of cosmetic formulations while maintaining the skin's natural moisture balance. Hydrogenated Lecithin also supports the skin's barrier function, enhancing its ability to retain moisture and protect against environmental aggressors. Its gentle, non-irritating nature makes it ideal for use in products designed for sensitive or dry skin.

[0075] Lauroyll Lysine is an amino acid-based ingredient used in cosmetic formulations for its skin-conditioning properties. It helps to improve theskin's moisture retention by forming a protective barrier on the skin’s surface. Additionally, Lauroyll Lysine helps to maintain the skin's natural pH balance, preventing dehydration and promoting a smooth, soft texture. It is often used in products targeting dry or damaged skin, as it helps to restore skin’s hydration levels while improving overall skin health.

[0076] Polyglyceryl-10 Oleate is a plant-derived emulsifier and skin-conditioning agent that helps to stabilize emulsions and improve the sensory properties of skincare products. This ingredient functions to hydrate and soften the skin, making it suitable for dry or sensitive skin types. Polyglyceryl-10 Oleate helps to restore the skin’s natural moisture balance, leaving it feeling smooth and nourished. It also supports the delivery of active ingredients, enhancing their penetration and efficacy.

[0077] Ectoin is a naturally occurring protective molecule that helps to condition the skin by stabilizing cell membranes and preventing dehydration. It is known for its ability to protect skin cells from environmental stressors, such as UV radiation and pollution. Ectoin enhances the skin’s moisture retention and supports its natural defense mechanisms, making it an excellent ingredient for soothing and moisturizing formulations. It is particularly beneficial for sensitive or stressed skin and helps to improve skin resilience.

[0078] Pentylene Glycol is a humectant and skin-conditioning agent used in cosmetic formulations to attract moisture to the skin and maintain hydration. It helps to improve the texture and feel of the product, providing a smooth, non-greasy finish. Pentylene Glycol also has antimicrobial properties that help to preserve the integrity of formulations, making it a multifunctional ingredient commonly used in moisturizers, serums, and cleansers.

[0079] Triheptanoin is a triglyceride derived from heptanoic acid, used as an emollient and skin-conditioning agent. It helps to smooth and hydrate the skin by forming a protective barrier that prevents moisture loss.

[0080] Triheptanoin is often used in lightweight formulations that require fast absorption without leaving a greasy residue. Its nourishing properties make it suitable for a range of skin types, including dry and sensitive skin, providing long-lasting hydration.Shea Butter is a rich, plant-derived fat known for its exceptional skinconditioning properties. It deeply moisturizes and nourishes the skin, restoring elasticity and improving skin texture. Shea Butter is rich in vitamins and fatty acids that help to soothe dry, irritated skin and promote healing. It also strengthens the skin’s natural barrier, preventing moisture loss and protecting the skin from environmental stressors. Due to its rich, emollient nature, Shea Butter is commonly used in moisturizers, balms, and creams designed for dry or aging skin.

[0081] Polyglutamic Acid is a powerful humectant that helps to condition the skin by attracting and retaining moisture. It has been shown to have superior moisture-binding properties compared to hyaluronic acid, and it supports the skin’s natural hydration levels by forming a protective film that locks in moisture. Polyglutamic Acid also helps to smooth the skin’s surface, reducing the appearance of fine lines and improving overall skin texture. Honokiol is a polyphenolic compound extracted from Magnolia bark with potent antioxidant and anti-inflammatory properties. In skincare formulations, it helps to condition the skin by reducing oxidative stress and inflammation, which can contribute to premature aging and skin damage. Honokiol also supports the skin’s natural barrier function, providing a calming and soothing effect, especially in products designed for sensitive or stressed skin.

[0082] Caprylyl Glycol is a multifunctional ingredient that acts as a skinconditioning agent, emollient, and preservative booster. It helps to hydrate the skin by attracting moisture and forming a protective layer to lock it in. Caprylyl Glycol also improves the texture and feel of formulations, leaving the skin smooth and soft. Its mild, non-irritating properties make it suitable for sensitive skin types, and it is often used in moisturizers, serums, and other hydrating skincare products.

[0083] Glycerin is a highly effective humectant and solvent used in cosmetics to attract moisture from the air and bind it to the skin. This ingredient helps to maintain the skin’s natural hydration balance by drawing water into the outer layers of the skin. Glycerin also acts as a solvent, dissolving and facilitating the delivery of other active ingredients in a formulation. Its soothing and moisturizing properties make it suitable for all skin types, particularly dry or sensitive skin.Glycerin is not only a powerful humectant and solvent but also acts as a stabilizer for fragrances in cosmetic formulations. It helps to dissolve and evenly distribute perfume compounds, ensuring the fragrance is evenly released upon application. Additionally, glycerin aids in moisturizing the skin, leaving it feeling soft and hydrated while enhancing the sensory experience of fragranced products.

[0084] Octyldodecanol is often included in perfumed cosmetic formulations for its ability to solubilize fragrances and improve the texture and spreadability of the product. As an emollient, it helps deliver a silky, non-greasy finish while enhancing the fragrance profile. Its mild and skin-conditioning properties make it ideal for use in high-end perfumed skincare and body care products.

[0085] Viscosity Controlling / Gel Forming

[0086] C12-16 Alcohols, a blend of fatty alcohols, are widely used in cosmetics for viscosity control and gel formation. They help to thicken formulations, improving the texture and stability of emulsions, gels, and creams. These alcohols also enhance the spreadability of products and contribute to a smooth, non-greasy finish, making them ideal for use in skin care, hair care, and body care formulations.

[0087] Oleic, Linoleic, and Linolenic Polyglycerides serve dual functions in cosmetics: as viscosity controllers and emulsifiers. These ingredients contribute to the smooth, stable consistency of emulsions by reducing surface tension between water and oil phases. Additionally, they help improve the texture and feel of products, enhancing their spreadability while promoting skin hydration and nourishment.

[0088] Carbomer is a synthetic polymer used in cosmetics as a viscosity enhancer and gel-forming agent. It is effective in thickening aqueous formulations, providing a gel-like texture that is smooth and easily applied. Carbomer is widely used in creams, gels, and lotions, as it helps stabilize emulsions and control product consistency. It also aids in the dispersion of active ingredients, ensuring their uniform application and absorption.

[0089] Lauroyll Lysine functions as a mild gel-forming agent and viscosity enhancer. It helps to stabilize emulsions and thickens formulations without causing irritation. Its gentle, skin-friendly nature makes it ideal for sensitive skin products. Lauroyll Lysine also supports hydration by forming a barrierthat prevents moisture loss, contributing to the overall texture and feel of the final product.

[0090] Xanthan Gum is a natural polysaccharide that is commonly used in cosmetics as a thickening and gel-forming agent. It improves the viscosity and texture of formulations, giving them a smooth, gel-like consistency. Xanthan Gum also stabilizes emulsions and enhances the spreadability of creams, lotions, and gels. Its ability to retain moisture makes it beneficial for hydrating skincare products.

[0091] Stearalkonium Hectorite is a naturally derived clay used for viscosity control in cosmetic formulations. It helps to thicken and stabilize emulsions and gels, improving the overall texture and sensory experience of the product. This ingredient also enhances the performance of other emulsifiers and stabilizers, contributing to the product's long-term stability and consistency. Propylene Carbonate is a solvent and viscosity control agent used in cosmetic formulations to enhance the texture and stability of gels and emulsions. It helps to dissolve other ingredients, allowing for a smooth and even distribution of actives. Additionally, it aids in adjusting the viscosity of the formulation, ensuring the desired texture and flow properties.

[0092] Dilinoeic Acid / Butanediol Copolymer is a film-forming agent used in cosmetics to create a flexible, protective layer on the skin. It helps to improve the longevity of cosmetic products by enhancing their adherence to the skin, reducing the need for frequent reapplication. This copolymer also contributes to the overall texture of the product, providing a smooth, non-sticky finish.

[0093] Castor Oil / IPDI Copolymer is a film-forming agent that creates a durable, flexible layer on the skin's surface. This copolymer enhances the wearability and longevity of cosmetic formulations, such as lipsticks, mascaras, and sunscreens. By improving adhesion, it ensures that the product stays in place for extended periods, providing long-lasting effects while also nourishing and conditioning the skin.

[0094] Niacinamide (Vitamin B3) is a versatile ingredient known for its ability to smooth and improve the skin’s texture. It helps to reduce the appearance of fine lines and wrinkles by promoting collagen production and improving the skin's elasticity. Niacinamide also helps to even out skin tone, reducingredness and pigmentation, making it an excellent smoothing agent for uneven or textured skin. Its anti-inflammatory properties further help to calm and soothe the skin, contributing to a more refined and smooth appearance.

[0095] Water is the most common solvent used in cosmetic formulations. It acts as a medium to dissolve and deliver other ingredients to the skin. Water helps to hydrate and condition the skin, providing moisture while allowing active ingredients to be more easily absorbed. As a solvent, water is essential in the formulation of creams, lotions, shampoos, and other cosmetic products, ensuring the proper consistency and stability of the final product.

[0096] Propandiol is a skin-friendly solvent that helps to dissolve other ingredients in cosmetic formulations. It serves as a humectant, attracting moisture to the skin and contributing to hydration. Additionally, propandiol enhances the texture of the product and improves its spreadability, providing a smooth and silky feel without being greasy.

[0097] Propylene Carbonate is a solvent used in cosmetics to dissolve and stabilize other ingredients. It helps to adjust the texture and viscosity of formulations while enhancing the delivery of active ingredients to the skin. As a mild solvent, it is often used in gels, creams, and serums, improving the overall performance of the product.

[0098] 1 ,2-Hexanediol is a solvent and humectant that aids in dissolving active ingredients and improving the texture of cosmetic formulations. It also contributes to moisture retention in the skin by attracting water from the environment. Additionally, 1,2-Hexanediol has antimicrobial properties, helping to preserve the integrity of cosmetic formulations while enhancing the delivery and absorption of other ingredients.

[0099] In certain embodiments of the invention the novel formulations of the invention increase SKPs proliferation and health which results in the reduction of sagging neck skin.

[0100] In certain embodiments of the invention the novel formulations of the invention increase SKPs proliferation and health which results in the reduction of the number and depth of crows feet wrinkles.

[0101] EXAMPLESExample 1.

[0102] Following previous work published on cultured human foreskin cells which showed a 40% increase in SKPs cell numbers at 100nM after 7 days (Naska et al) further testing of various kaempferol concentrations was conducted on cultured human SKPs from middle to aged people. 100nM was efficacious for newborns which would translate into an 0.05% optimal dose on humans if we were treating newborns and not adults.

[0103] The instant example was an adult human SKP proliferation drug study conducted on SKPs isolated from human scalp skin samples from subjects aged from 58-77 years. There were 5 female and 1 male subjects.

[0104] In this experiment, sphere number corresponds to numbers of SKPs stem cells while the sphere size corresponds to proliferation of individual stem cells. In this experiment a 1uM concentration worked in 4 of 6.

[0105] The experiments used 2-3 SKPs at a 10,000 cells / ml density. Sphere counts were based on colonies exceeding 50pm in diameter.

[0106] The results were:

[0107] 58 year old female: 1uM and 5uM increased stem cell number

[0108] 58 year old female, 1uM increased stem cell number

[0109] 64 year old female, 100nM increased stem cell number

[0110] 60 year old female, 5uM increase in stem cell proliferation

[0111] 77 year old male, 1uM increased stem cell number, and 100nM and 1uM increased stem cell proliferation

[0112] 58 year old female, 1uM increased stem cell number

[0113] The data was pooled and the results are shown in Figure 1 and In this example as shown in the pooled in vitro data 100nM was effective although 1uM was optimal.

[0114] Certain embodiments of the invention comprise methods of enhancing the proliferation of skin-derived precursors (SKPs) by administering kaempferol at a concentration of less than 1 uM.Certain embodiments of the invention comprise methods of enhancing the proliferation of skin-derived precursors (SKPs) by administering kaempferol at a concentration of less than 100nM.

[0115] Example 2.

[0116] Building on the results of Example 1 and previous in vitro research and recognizing that humans have thick skin careful formulation was used to radically depart from previous research to obtain an optimal cream cosmetic formulation for commercial use that would take advantage of kaempferol’s surprising ability to increase skin stem cell numbers and size.

[0117] In the instant invention, the safety and efficacy of a kaempferol cream formulation at 0.026% (1mM) (20-fold less than the equivalent optimal concentration of kaempferol on cultured mouse SKPs and within two-fold of the equivalent lowest 100nM concentration of Example 1) was tested.

[0118] A cream containing a low dose of kaempferol as well hyaluronic acid, tocopherol, and moringa extract was tested on a panel of 42 women over a 28-day period, with applications in both the morning and evening. The cream also contained additional emollients, emulsifiers, stabilizing agents, surfactants, skin conditioning agents, solvents, smoothing agents, cleansing agents and perfuming agents as outline in Table 1.

[0119] In addition to self-reporting of results a Primos 3-dimensional instrumental measurement technique was used to objectively measure changes in crow’s feet on the outer edge of the eye.

[0120] The cream was tested on 42 female volunteers with a minimum age of 46 and a maximum age of 69. Average age was 62.9, median was 64.0 and mode was 70.0. Only 25% of the pool was 59 or younger, and only two participants were in their late 40s. This is an older age group, and the fact that the promising results described below were recorded in this population is striking and notable.Self-testing results indicated there was a significant reduction in sagging neck skin at both day 7 and day 28.

[0121] By day 28, there was a significant reduction in crow’s-feet wrinkles was observed, demonstrating the cream’s ability to deliver both a smoothing and tightening effect. This result was obtained using the objective measurement by Primos which measures the depth of wrinkles and the cream's smoothing ability.

[0122] Test subjects provided overwhelmingly positive feedback on the results they achieved with the cream in a questionnaire. Over 90% of participants (at least 38 women) provided positive feedback on their subjective experience with the kaempferol cream.

[0123] “My skin looks regenerated” 98%

[0124] “My skin looks softer and smoother” 95%

[0125] “My skin looks more nourished / moisturized” 95%

[0126] “The product improves the way my skin feels” 90%Table 1.

[0127] Ingredient Function Amount (%) KAEMPFEROL SKP activator 0.026 HYDROLYZED Skin conditioner 0.173 HYALURONIC ACID MORINGA OLEIFERA SEED Skin conditioner 0.050 EXTRACT VACCINIUM astringent 0.023 MACROCARPON

[0128] (CRANBERRY) FRUIT

[0129] EXTRACT TOCOPHEROL antioxidant 0.200 WATER solvent 62.464 NIACINAMIDE smoothing 5.000 PROPANEDIOL solvent / viscosity controlling 5.000 GLYCERIN denaturant / humectant / 4.740

[0130] perfuming / solvent OCTYLDODECANOL emollient / perfuming / 4.500

[0131] solvent

[0132] BUTYROSPERMUM PARKII skin conditioning / viscosity 4.000 (SHEA) BUTTER controlling

[0133] PENTYLENE GLYCOL skin conditioning / solvent 2.000 SQUALANE emollient / hair conditioning 2.000

[0134] / refatting

[0135] / skin conditioning

[0136] C14-22 ALCOHOLS emulsion stabilising 1.590 TRIHEPTANOIN skin conditioning / surfactantO.817

[0137] / viscosity controlling

[0138] GLYCERYL STEARATE emollient / emulsifying 0.800 GLYCERYL CAPRYLATE emollient / emulsifying 0.700 DICAPRYLYL CARBONATE emollient / skin conditioning 0.696 COCO- emollient / skin conditioning 0.525 CAPRYLATE / CAPRATE

[0139] LAUROYL LYSINE hair conditioning / skin 0.500

[0140] conditioning / viscosity

[0141] controllingTable 1. Continued

[0142] OLEIC / LINOLEIC / LINOLEN binding / emollient /

[0143] IC POLYGLYCERIDES emulsion stabilising / 0.500 surfactant / viscosity controlling

[0144] SODIUM STEAROYL cleansing / emulsifying / hair 0.500 GLUTAMATE conditioning / skin conditioning

[0145] antistatic / emollient /

[0146] C12-16 ALCOHOLS emulsion stabilising / hair 0.450 conditioning / viscosity controlling

[0147] C12-20 ALKYL GLUCOSIDE emulsifying / surfactant 0.410 CARBOMER emulsion stabilising / gel 0.400 forming / viscosity

[0148] controlling

[0149] APRICOT KERNEL OIL emollient / emulsifying / skin 0.217 conditioning / surfactant ECTOIN skin conditioning 0.200 POLYGLYCERYL-6 OLEATE emulsifying 0.199 POLYGLYCERYL- 10 skin conditioning 0.191 OLEATE DILINOLEIC film forming / plasticiser 0.150 ACID / BUTANEDIOL

[0150] COPOLYMER HYDROGENATED emulsifying / skin 0.150 LECITHIN conditioning

[0151] PALMITIC ACID emollient / emulsifying 0.150 SODIUM BENZOATE anticorrosive / masking / 0.100 preservative

[0152] XANTHAN GUM binding / emulsifying /

[0153] emulsion stabilising / gel 0.100 forming / skin conditioning / surfactant / viscosity controlling

[0154] SODIUM PHYTATE chelating / oral care 0.080 STEARALKONIUM gel forming / viscosity 0.080 HECTORITE controllingTable 1. Continued

[0155] POLYGLUTAMIC ACID skin conditioning 0.075

[0156] SORBITAN PALMITATE emulsifying 0.069

[0157] absorbent / binding /

[0158] MALTODEXTRIN emulsion stabilising / film 0.05

[0159] forming / hair conditioning /

[0160] skin conditioning

[0161] SODIUM HYDROXIDE buffering / denaturant 0.038

[0162] PROPYLENE CARBONATE solvent / viscosity controlling 0.024

[0163] HONOKIOL antioxidant / bleaching / skin 0.017

[0164] conditioning

[0165] MAGNOLOL antioxidant / bleaching 0.017

[0166] 1.2-HEXANEDIOL solvent 0.010

[0167] CAPRYLYL GLYCOL emollient / hair conditioning 0.010

[0168] / humectant / skin

[0169] conditioning

[0170] CASTOR OIL / IPDI film forming 0.008

[0171] COPOLYMER

[0172] Table 2. Primos Results

[0173]

[0174]

[0175] Example 3.

[0176] In this example the level of kaempferol was increased by a factor of 3 over Example 2 to 3mM or 0.078%. Additional ingredients included Moringa Oleifera seed extract, sodium hyaluronate, hydrolyzed hyaluronic acid, and tocopherol.

[0177] In addition, the following cosmetic ingredients were added: water (Aqua), Niacinamide, Octyldodecanol, Butyrospermum Parkii (Shea) Butter, Glyceryl Stearate, Squalane, Pentylene Glycol, Sodium Stearoyl Glutamate, Cetearyl Alcohol, Cetearyl Glucoside, Triheptanoin, Lecithin, C12-16 Alcohol, Palmitic Acid, Lauroyl Lysine, Oleic / Linoleic Polyglycerides, Tocopherol, Dilinoleic Acid / Butanediol Copolymer, Polyglutamic Acid Maltodextrin, Castor Oil / IPDI Copolymer, Ectoin, Carbomer, Sodium Phytate, Capryl hydroxamic Acid, Caprylyl Glycol, Vaccinium Macrocarpon (Cranberry) Fruit Extract, Magnolol, Honokiol, Polyglyceryl- 10 Oleate, Polyglyceryl-6 Oleate, Apricot Kernel Oil, Polyglyceryl-6 Esters, Sorbitan Palmitate, Dicetyl Phosphate.

[0178] It is noted that the foregoing has outlined some of the more pertinent nonlimiting embodiments. These non-limiting embodiments may be used for many applications. Thus, although the description is made for particular arrangements and methods, the intent and concept of these non-limiting embodiments may be suitable and applicable to other arrangements and applications. It will be clear to those skilled in the art that modifications to the disclosed non-limiting embodiments can be effected. The described non-limiting embodiments ought to be construed to be merely illustrative of some of the more prominent features and applications thereof. Other beneficial results can be realized by applying these non-limiting embodiments in a different manner or modifying them in ways known tothose familiar with the art. This includes the mixing and matching of features, elements and / or functions between various non-limiting embodiments is expressly contemplated herein, unless described otherwise, above.

[0179] All publications, patent applications, and patents mentioned in this specification are herein incorporated by reference to the same extent as if each independent publication, patent application, or patent was specifically and individually indicated to be incorporated by reference.

Claims

Claims:

1. A topical composition for enhancing the proliferation of skin stem cells comprising kaempferol, hyaluronic acid plus optionally sodium hyaluronate, and Moringa extract.

2. The composition according to claim 1 further comprising antioxidants, emollients, emulsifiers, stabilizing agents, surfactants, skin conditioning agents, surfactants, solvents, smoothing agents, cleansing agents and perfuming agents are included.

3. The composition according to claim 2 wherein the formulation comprises the ingredients in Table 1.

4. The composition according to any of the previous claims wherein the kaempferol is present in a dose of less than 3m M or 0.08%.

5. The composition according to claim 4 wherein the kaempferol is present in a dose of less than 1mM or 0.03%.

6. The composition according to any of the previous claims wherein the composition reduces wrinkles and sagging skin.

7. The composition according to claim 6 wherein the wrinkles are neck wrinkles, crows feet wrinkles forehead wrinkles, cheek wrinkles or other facial wrinkles.

8. The composition according to claim 7 wherein the wrinkles are crows feet wrinkles.

9. The composition according to claim 6 wherein the sagging skin is on the neck.

10. The composition according to claim 2 or claims 4 to 9 wherein the formulation includes water, niacinamide, octyldodecanol, butyrospermum parkii (shea) butter, glyceryl stearate, squalane, pentylene glycol, sodium stearoyl glutamate, cetearyl alcohol, cetearyl glucoside, triheptanoin, lecithin, c12-16 alcohol, palmitic acid, lauroyl lysine, oleic / linoleic polyglycerides, tocopherol, dilinoleic acid / butanediol copolymer, polyglutamic acidmaltodextrin, castor oil / ipdi copolymer, ectoin, carbomer, sodium phytate, capryl hydroxamic acid, caprylyl glycol, vaccinium macrocarpon (cranberry) fruit extract, magnolol, honokiol, polyglyceryl-10 oleate, polyglyceryl-6 oleate, apricot kernel oil, polyglyceryl-6 esters, sorbitan palmitate, and dicetyl phosphate.

11. A method of reducing crows feet wrinkles comprising administering a composition according to any of claims 1 through 10 at least twice per day for at least 28 days.

12. A method of reducing sagging skin on the neck of a subject by administering a composition according to any of claims 1 through 10 at least twice per day for at least 7 days.

13. A method of reducing sagging skin on the neck of a subject by administering a composition according to any of claims 1 through 10 at least twice per day for at least 28 days.

14. The composition according to claim 2 wherein the emollients are selected from c12-16 alcohols, oleic / linoleic / linolenic polyglycerides, palmitic acid, glyceryl caprylate, glyceryl stearate, apricot kernel oil, polyglyceryl-6 esters, squalane, dicaprylyl carbonate, octyldodecanol, and caprylyl glycol.

15. The composition according to claim 2 wherein the emulsifiers are selected from c12-16 alcohols, oleic / linoleic / linolenic polyglycerides, sodium stearoyl glutamate, palmitic acid, glyceryl caprylate, glyceryl stearate, apricot kernel oil, polyglyceryl-6 oleate, hydrogenated lecithin, c12-20 alkyl glucoside, carbomer, xanthan gum, sorbitan palmitate, and maltodextrin.

16. The composition according to claim 2 wherein the stabilizing agents are selected from c12-24 alcohols, oleic / linoleic / linolenic polyglycerides.

17. The composition according to claim 2 wherein the surfactant are selected from oleic / linoleic / linolenic polyglycerides, apricot kernel oil polyglyceryl-6 esters, and c12-20 alkyl glucoside.

18. The composition according to claim 2 wherein the cleansing agent is sodium stearoyl glutamate.

19. The composition according to claim 2 wherein the skin conditioning agents are selected from sodium stearoyl glutamate, apricot kernel oil polyglyceryl-6 esters, squalane, coco-caprylate / caprate, dicaprylyl carbonate, octyldodecanol, hydrogenated lecithin, lauroyl lysine, polyglyceryl-10 oleate, ectoin, pentylene glycol, triheptanoin, butyrospermum parkii (shea) butter, polyglutamic acid, maltodextrin, honokiol, and caprylyl glycol.

20. The composition according to claim 2 wherein perfuming agents are included and are selected from glycerin and octyldodecanol.

21. The composition according to claim 2 wherein the viscosity control I ing / gel forming agents are selected from c12-16 alcohols, oleic / linoleic / linolenic polyglycerides, carbomer, lauroyl lysine, xanthan gum, stearalkonium, hectorite, and propylene carbonate.

22. The composition according to claim 2 wherein the film forming agents are selected from dilinoleic acid / butanediol copolymer and castor oil / ipdi copolymer.

23. The composition according to claim 2 wherein the smoothing agent is niacinamide.

24. The composition according to claim 2 wherein the solvents are selected from water, propanediol, propylene carbonate, 1 ,2- hexanediol, and glycerin.

25. The composition according to claim 2 wherein preservatives such as sodium benzoate are included.

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