RU2793250C2 - Composition and methods for treatment of skin pathological conditions, using light and glucosamine hydrochloride - Google Patents

Abstract

FIELD: cosmetic industry.

SUBSTANCE: method for increasing the production of hyaluronic acid in human skin fibroblasts. A method for increasing the production of hyaluronic acid in human skin fibroblasts, comprising topical application of a topical composition to human skin and simultaneous exposure of this skin to red light with a peak wavelength of 633 nm and near infrared light with a peak wavelength of 830 nm, using a light supply device at a light intensity of 0.3 J/cm² or 3 J/cm², wherein the topical composition contains 0.02 weight percent glucosamine hydrochloride and has a pH of 3.0 to 5.5. A method for increasing the production of hyaluronic acid in human skin fibroblasts, comprising topical application of a topical composition to human skin and simultaneous exposure of this skin to red light with a peak wavelength of 633 nm and near infrared light with a peak wavelength of 830 nm, using a light supply device at a light intensity of 0.3 J/cm² or 3 J/cm², wherein the topical composition contains 0.2 weight percent glucosamine hydrochloride and has a pH of 3.0 to 5.5.

EFFECT: methods effectively increase the production of hyaluronic acid in human skin fibroblasts.

6 cl, 7 tbl, 5 ex

Description

Scope of the invention

Hyaluronic acid is present in all connective tissues. In the skin, it is produced by fibroblasts and keratinocytes. Hyaluronic acid can bind up to 1,000 times its own weight in water, helping the skin retain and retain water. In young skin, hyaluronic acid is located at the periphery of collagen and elastin fibers and at the points where these fibers intersect. Aging skin, which is less dense than young skin, is characterized by lower levels of hyaluronic acid. This reduced level of hyaluronic acid contributes to the binding of hyaluronic acid to collagen and elastin, and also reduces water binding. Thus, reduced levels of hyaluronic acid are implicated in the signs of skin aging, including wrinkles, altered elasticity, reduced turbidity, and reduced ability to maintain skin microcirculation. The main clinical signs of skin aging in particular include the appearance of fine lines and wrinkles that increase with age.

Various products and methods have been proposed to combat wrinkles and fine lines, and hyaluronic acid itself is used commercially as an active agent in both injectable and topical cosmetic products to increase skin hydration and elasticity. However, hyaluronic acid can remain on the surface of the skin for a limited time (as well as when injected into the skin). Hyaluronidases, enzymes present on the surface of the skin, break down hyaluronic acid and thus reduce its effect. The half-life of hyaluronic acid varies depending on the tissue, but is about one day in the dermis and epidermis. Moreover, penetration of exogenous hyaluronic acid into the skin has been found to be difficult to achieve with topical application.

Glucosamine in oral supplement form is available to support joint structure and function in humans and animals. Commonly marketed forms of glucosamine are glucosamine sulfate, glucosamine hydrochloride, and N-acetylglucosamine.

Glucosamine is used in some oral supplements to treat joint pain, but it is not widely used in skin care.

It is known that light therapy is effective in the treatment of pathological conditions of the skin, it is also known that red light with a wavelength of about 633 nm has an anti-inflammatory effect. It is believed that the mechanism of anti-inflammatory action of red light is based on the inhibition of inflammatory mediators and enzymes such as interleukin-1a and matrix metalloproteinases.

US 8,771,328 describes advanced phototherapy systems comprising a therapeutic lamp platform for emitting lamps, such as LEDs, located in a suitable device, which may be in the form of a face mask. The system emits radiant energy of various wavelengths, for example at least two of the blue, red or infrared spectrum.

NEUTROGENA Light Therapy Acne Mask, sold by Johnson & Johnson Consumer Inc., emits blue light that penetrates just below the surface of the skin to kill acne-causing bacteria and red light that penetrates deeper into the skin to reduce inflammation.

US 7,066,941 relates to the treatment of aging or damaged skin by irradiating it with some effective amount of visible light having a wavelength of about 400 nm to about 500 nm. The light source can be, for example, sunlight or artificial light, and in one embodiment, light emitting diodes are applied to selected areas of the skin. Compositions containing compounds that improve the light permeability of the stratum corneum, such as alpha hydroxy acids and/or a light filter, may be applied to the skin before or during phototherapy.

WO 2016/146778 relates to cosmetic methods of providing skin care, comprising illuminating the skin of a subject with one or more beams of light, which cause light to enter the skin having a discrete spectrum with peaks in wavelengths corresponding to green light, red light and near infrared light, along with a topical composition which may contain a wide range of ingredients including glucosamine. Such methods are believed to be useful in activating skin processes including skin cell proliferation and migration and production of extracellular matrix fibers such as collagen.

Applicants have discovered that skin production of hyaluronic acid can be unexpectedly increased by applying a topical composition containing up to about 2% by weight of glusamine hydrochloride and exposing said skin to red and near infrared light using a light delivery device, providing significant and unexpected benefits. for the skin, including improving, slowing down or delaying the appearance of at least one sign of skin aging. This combination can also enhance skin barrier function and skin hydration. Accordingly, new treatments are now available for, for example, signs of skin aging.

Statement of the Invention

The present invention provides a method of increasing the production of hyaluronic acid in the skin, comprising topically applying to such skin a topical composition containing up to about 2% by weight of glusamine hydrochloride and exposing said skin to red light with a peak wavelength of from about 600 nm to about 750 nm, near infrared light with a peak wavelength of about 750 nm to about 1000 nm, or both, using a light delivery device.

The present invention also provides a method of treating skin, comprising topical application to skin in need of treatment for signs of skin aging, topical compositions containing up to about 2% by weight of glusamine hydrochloride and exposing said skin to red light with a peak wavelength of about 600 nm to about 750 nm, near infrared light with a peak wavelength of about 750 nm to about 1000 nm, or both using a light supply device.

The present invention further provides a method for treating skin, comprising topical application to skin in need of hydration, compositions for topical application containing up to about 2% by weight of glusamine hydrochloride and exposing said skin to red light with a peak wavelength from about 600 nm to about 750 nm, near infrared light with a peak wavelength from about 750 nm to about 1000 nm, or both using a light supply device.

The invention also includes a kit containing: (a) a topical composition containing up to about 2% by weight of glucosamine hydrochloride, and (b) a light delivery device that delivers red light at a peak wavelength of about 600 nm to about 750 nm, near infrared light with a peak wavelength of about 750 nm to about 1000 nm, or both.

The invention further provides a topical composition comprising about 0.1 to about 2% by weight of glusamine hydrochloride and at least one compound having a pKa of about 2.5 to about 4.5, said composition having a pH of less than about 5.5.

The invention also provides a film comprising a topical composition comprising from about 0.1 to about 2% by weight of glusamine hydrochloride and at least one compound having a pKa of from about 2.5 to about 4.5, said composition having pH less than about 5.5.

Detailed description of the invention

Unless otherwise indicated, all technical and scientific terms used herein have the common meaning understood by any person of ordinary skill in the art to which the present invention pertains. All publications, patent applications, patents and other references mentioned in this document are incorporated herein by reference.

As used herein, the term "topical application" refers to direct application or spread over the outer surface of the skin or scalp, for example by hand or with an applicator such as a tissue, roller or spray.

As used herein, the term "cosmetic" refers to an appearance-enhancing substance or preparation that maintains, restores, imparts, mimics or enhances physical attractiveness, or has an attractive or youthful effect, especially with respect to the appearance of tissue or skin.

As used herein, the term "cosmetically effective amount" means an amount of a physiologically active compound or composition sufficient to treat one or more conditions, but low enough not to cause serious side effects. The cosmetically effective amount of a compound or composition will vary depending on 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 treatment, the nature of other treatment options, the particular compound or product/composition employed, the specific cosmetically acceptable carrier used; and the like.

As used herein, the term "cosmetically acceptable" means that the ingredients that the term describes are acceptable for use in contact with tissues (e.g., skin) without undesirable toxicity, incompatibility, instability, irritation, allergic reactions, etc.

As used herein, the term "cosmetically acceptable active agent" means a composition (synthetic or natural) that has a cosmetic or therapeutic effect on the skin.

As used herein, the term "treatment or therapy" refers to reducing, alleviating, preventing, correcting, or eliminating the symptoms of a condition or disorder.

The present invention is suitable for reversing signs of skin aging. As used herein, the term "signs of skin aging" refers to the presence of folds and wrinkles, loss of elasticity, uneven skin tone, and patchiness. In a particularly preferred embodiment, a sign of aging is the presence of folds, wrinkles and/or loss of elasticity.

As used herein, the term "wrinkle" includes fine lines, fine lines, or deep lines. Examples of wrinkles include, but are not limited to, fine lines around the eyes (eg, crow's feet), wrinkles on the forehead and cheeks, frown lines, and expression lines around the mouth.

As used herein, the term "loss of elasticity" refers to loss of elasticity or integrity of a skin or tissue structure, including, without limitation, tissue sagging, laxity, and laxity. Loss of elasticity or integrity of the tissue structure may result from a number of factors, including, but not limited to, disease, aging, hormonal changes, mechanical trauma, environmental stress, or may result from the application of products such as cosmetics or pharmaceuticals to the tissue.

As used herein, the term "uneven skin tone" means a skin condition associated with diffuse or patchy pigmentation, which can be considered hyperpigmentation, such as post-inflammatory hyperpigmentation.

As used herein, the term "spotting" refers to a skin condition associated with redness or erythema.

The compositions of the invention are also used to treat skin in need of hydration. As used herein, the term “skin in need of hydration” means skin that is characterized, without limitation, by moisture deficiency, sebum deficiency, cracking, dryness, itching, flaking, xeroderma, dehydration, lack of flexibility, lack of luster, dullness, or lack of lipids. .

Unless otherwise indicated, a percentage or concentration is indicated as a percentage or concentration by weight (ie, % w/w). Unless otherwise noted, all ranges are subject to limit values, for example, the range "4 to 9" includes limits 4 and 9.

Topical composition containing glucosamine hydrochloride

The present invention uses a topical composition containing glucosamine hydrochloride.

The topical composition may contain up to about 2% by weight, preferably up to about 1.5% by weight, or more preferably up to about 1% by weight, of glucosamine hydrochloride.

Glucosamine is available in various forms, including various salts and derivatives. The inventors have found that not all forms of glucosamine provide excellent effects when combined with infrared and/or red light. Surprisingly, it has been found that the administration of glusamine hydrochloride with infrared and/or red light synergistically increases the production of hyaluronic acid. This has not been observed with glucosamine phosphate, N-acetylglucosamine, or glucosamine.

Glucosamine hydrochloride is commercially available from, for example, Sigma Aldrich.

The composition may optionally contain a wide variety of additional fat soluble materials and/or water soluble materials conventionally used in skin care compositions at concentrations known to those skilled in the art. For example, surfactants, perlescent agents or opacifiers, thickeners, softeners, conditioners, humectants, chelating agents, scrubs, and additives that enhance the appearance, feel, and aroma of the composition, such as coloring agents, fragrances, preservatives, regulators, may be included. pH, etc.

The composition may contain one or more other cosmetically acceptable active agents, including, for example, anti-aging or moisturizing agents, acne treatment agents, gloss control agents, antimicrobial agents, anti-inflammatory agents, antifungal agents, antiparasitic agents, topical analgesics. , sunscreens, photoprotectors, antioxidants, keratolytic agents, surfactants, nutrients, vitamins, energy boosting agents, antiperspirant agents, astringents, deodorants, plumping agents, anti-corn agents, skin conditioning agents and skin whitening agents.

The amount of cosmetically active agent may be in the range from about 0.001% to about 20% wt. compositions, for example from about 0.005% to about 10% wt. compositions, for example from about 0.01% to about 5% wt. compositions.

The cosmetically acceptable active agent may be selected from, for example, benzoyl peroxide, D-panthenol, carotenoids, ceramides, polyunsaturated fatty acids, essential fatty acids, enzymes such as laccase, enzyme inhibitors, minerals, hormones such as estrogens, steroids such as hydrocortisone, 2-dimethylaminoethanol, copper salts such as copper chloride, peptides such as argireline, Syn-ake and copper-containing peptides, coenzyme Q10, amino acids such as proline, vitamins, lactobionic acid, acetyl coenzyme A, niacin, riboflavin, thiamine, ribose, electron carriers such as NADH and FADH2, natural extracts such as aloe vera, feverfew, oats, dill, blackberry, paulownia tomentum, Picia anomala and chicory, resorcinols such as 4-hexylresorcinol, curcuminoids, amino sugars, such as N-acetylglucosamines, as well as their derivatives and mixtures.

Examples of vitamins include, without limitation, vitamin A, B vitamins such as vitamin B3, vitamin B5 and vitamin B12, vitamin C, vitamin K, and various forms of vitamin E such as alpha, beta, gamma, or delta tocopherols. or their mixtures, and their derivatives.

Examples of antioxidants include, without limitation, water-soluble antioxidants such as sulfhydryl compounds and their derivatives (e.g., sodium metabisulfite and N-acetylcysteine), lipoic acid and dihydrolipoic acid, resveratrol, lactoferrin, and ascorbic acid and ascorbic acid derivatives (e.g., ascorbyl palmitate). and ascorbyl polypeptide). Fat-soluble antioxidants suitable for use in the compositions of the present invention include butylated hydroxytoluene, retinoids (eg, retinol and retinyl palmitate), tocopherols (eg, tocopherol acetate), tocotrienols, and ubiquinone. Natural extracts containing antioxidants suitable for use in the compositions of the present invention include, without limitation, extracts containing flavonoids and isoflavonoids, as well as their derivatives (for example, genistein and diadzein), extracts containing resveratrol, and the like. Examples of such natural extracts include extracts of grape seed, green tea, pine bark and propolis.

In one embodiment, the topical composition contains at least about 4, or about 4 to about 20 weight percent glycerol, such as about 6 to about 10 weight percent glycerol.

In another embodiment, the topical composition contains from about 0.1 to about 2% by weight of glusamine hydrochloride and at least one compound having a pKa of from about 2.5 to about 4.5, said composition having a pH of less than about 5.5. For example, a compound having a pKa of about 2.5 to about 4.5 may be selected from the group consisting of citric acid, lactic acid, glycolic acid, succinic acid, and mixtures thereof.

In another embodiment, the topical composition further comprises sodium bisulfite.

The composition may further include a cosmetically acceptable topical carrier. The media can be from about 50% to about 99.99% wt. compositions (eg, from about 80% to about 99% by weight of the composition). In one embodiment, the cosmetically acceptable topical carrier comprises water.

The composition may be in the form of a variety of product types which include, but are not limited to, lotions, creams, gels, sticks, aerosols, ointments, pastes, foams, powders, mousses, creams, wipes, patches, hydrogels, film-forming products, face masks. and skin masks, dissolving or non-dissolving films and color cosmetics such as makeup bases. These types of products may contain a variety of cosmetically acceptable topical carriers, including, without limitation, solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, solids, films, and liposomes. The following are non-limiting examples of such carriers. Other carriers may be incorporated into the formulations by those skilled in the art.

The composition may be prepared as a solution. Solutions typically include an aqueous or organic solvent (eg, about 50% to about 99.99%, or about 90% to about 99% of a cosmetically acceptable aqueous or organic solvent). Examples of suitable organic solvents include propylene glycol, polyethylene glycol, polypropylene glycol, glycerol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol, and mixtures thereof.

The composition may be prepared as a solution containing a softener. Such compositions preferably contain from about 2% to about 50% softener(s). As used herein, the term "emollients" refers to substances used to prevent or eliminate dryness, for example by preventing transepidermal water loss from the skin. Examples of emollients include, without limitation, those listed in the International Cosmetic Ingredient Dictionary and Handbook, eds. Pepe, Wenninger and McEwen, pp. 2930-36 (The Cosmetic, Toiletry, and Fragrance Assoc., Washington, DC, 9th Edition, 2002) (hereinafter ICI Handbook). Examples of particularly suitable softeners include vegetable oils, mineral oils, fatty acid esters, and the like.

A lotion can be made from such a solution. Lotions typically contain from about 1% to about 20% (for example, from about 5% to about 10%) softener(s) and from about 50% to about 90% (for example, from about 60% to about 80 %) water.

Another type of product that can be prepared from a solution is a cream. Typically, a cream contains about 5% to about 50% (e.g., about 10% to about 20%) emollient(s) and about 45% to about 85% (e.g., about 50% to about 75% ) water.

The composition may alternatively be anhydrous or may be an ointment containing no water but containing organic and/or silicone solvents, oils, lipids and waxes. The ointment may contain a simple base of animal or vegetable oils or semi-solid hydrocarbons. The ointment may contain from about 2% to about 10% emollient(s) and from about 0.1% to about 2% thickener(s). Examples of thickeners include, without limitation, those listed in ICI Handbook pp. 2979-84.

The composition may be formulated as an emulsion. If the topical carrier is an emulsion, then about 1% to about 10% (eg, about 2% to about 5%) of the topical carrier is the emulsifier(s). Emulsifiers can be non-ionic, anionic or cationic. Examples of emulsifiers include, without limitation, those listed in ICI Handbook pp. 2962-71.

Lotions and creams can be prepared as emulsions. Typically, such lotions contain from 0.5% to about 5% emulsifier(s). Such creams typically contain about 1% to about 20% (eg, about 5% to about 10%) emollient(s); about 20% to about 80% (eg, 30% to about 70%) water; and about 1% to about 10% (eg, about 2% to about 5%) emulsifier(s).

Single phase emulsion based oil-in-water and water-in-oil skin care formulations, such as lotions and creams, are well known in the cosmetic field and can be used in the claimed invention. Compositions of the type "water-in-oil-in-water" or "oil-in-water-in-oil" based on a multi-phase emulsion are also used in the claimed invention. As such, such single or multi-phase emulsions contain water, softeners and emulsifiers as main ingredients.

The composition may also be formulated as a gel (eg, an aqueous, alcoholic, hydroalcoholic, or oily gel using a suitable gelling agent(s)). Suitable gelling agents for aqueous and/or alcoholic gels include, without limitation, natural gums, acrylic acid, and cellulose-derived acrylate polymers and copolymers (eg, hydroxymethylcellulose and hydroxypropylcellulose). Suitable gelling agents for oils (such as mineral oil) include, without limitation, hydrogenated butylene/ethylene/styrene copolymer and hydrogenated ethylene/propylene/styrene copolymer. In such gels, the content of these gelling agents, as a rule, is from about 0.1% to 5% wt.

The composition may also be prepared in solid form (eg wax stick, stick or powder).

The composition may be incorporated into a support such as a film, woven or nonwoven fabric, wipe, patch, mask, garment, and the like.

In one embodiment, the composition is contained in a film. As used herein, the term "film" means a composition that forms a thin layer or membrane on the skin of mammals, in particular human skin. Such a film may contain one layer or several layers.

In one embodiment, the film is a dissolvable film. A variety of dissolvable films are known in the art, and any of them can be used in accordance with the invention.

In one particular embodiment, the film may comprise an integral film product as described in US 2015/0182991, the disclosure of which is incorporated herein by reference. The integral film product is designed and configured to be removed from the manufacturing substrate on which it is made for use independently of the manufacturing substrate. In particular, the product can be made by placing a template on a manufacturing substrate having a releasable surface, applying a film-forming composition through the template to form a raw shape on the manufacturing substrate; deleting a template; and curing the raw form into a single film product located on a manufacturing substrate. The template has at least one hole, the shape of which corresponds to the shape of the desired integral film product. The integral film product is designed and configured to be removed from the releasable surface of the manufacturing substrate for use independently of it.

In another embodiment, the film is a multilayer shaped film product as described in US 2015/0182990, the disclosure of which is incorporated herein by reference. For example, a shaped bilayer film product may be used having a first surface containing a topical composition for delivery to the skin and a second surface facing outward. Such an article can be made using a method that includes applying liquid film-forming compositions through a template; removal of the template while maintaining the multi-layered raw form; and curing the multilayer raw form to form a multilayer shaped film product. The template has a feed surface, an opposite surface, and at least one hole, the shape of which corresponds to the desired shape of the film product. Film-forming compositions are applied through a multi-flow nozzle. The movement of the template and the supply of the first and second liquid film-forming compositions to the opening of the template is controlled so as to provide a volumetric flow rate of the first and second liquid film-forming compositions to the opening of the template, corresponding to the volume of empty space. The nozzle is in contact with the template feed surface.

In another specific embodiment, the film may be a multilayer film product as described in US 2015/0182992, the disclosure of which is incorporated herein by reference. For example, a two-layer shaped film product may be used in which the first layer has a larger surface area than the second layer located on the first layer. As a result, an “island” of the second layer is formed at the top of the first layer. One of the two layers is intended for contact with the skin and contains the composition of the invention. The other layer is facing the outside. Such an article can be made using a method that includes applying a first film-forming composition through a first template to form a first raw shape; deleting the first template; placing the second template above the first raw form; applying to the first raw form of the second film-forming composition through the second template with the formation of the second raw form; deleting the second template; and curing the first and second raw forms to obtain a shaped film product.

In an additional embodiment, a shaped film product as described in US 2015/0182993, the disclosure of which is incorporated herein by reference, may contain a composition. Such a shaped film product can be made by placing a template over a manufacturing substrate; applying the film-forming composition through a nozzle to form a raw form on the manufacturing substrate; deleting a template; and curing the film-forming composition to obtain a shaped film product placed on the manufacturing substrate. The template has an application surface and an opposite surface facing the production substrate, as well as at least one hole having a configuration corresponding to the desired shaped film product. The nozzle is placed in a sealed connection with the template application surface in relation to at least one template hole when applying the film-forming composition.

In another embodiment, you can use a multilayer film for local application, described in US 2016/0367490, the description of which is incorporated herein by reference. This film is made with the possibility of easy removal when water is applied to it. As used herein, the term "easy to remove" means that the film can dissolve or disintegrate when water is applied to it, so that the film can be removed from the skin without peeling or the like.

Such a film comprises a first top layer, the top surface of which is facing the outside of the skin, and a first bottom layer opposite the first top surface, which is facing the skin. The article also comprises a lower skin-contacting layer comprising a second upper surface facing and adhering to the first lower surface of the first upper layer, and a second lower surface that faces outward to contact and adhere the article to the skin when the article is applied to it. The lower skin-contacting layer contains a composition for topical application. In addition, each of the first top layer and the second bottom layer contains a water-soluble film former, and the product is designed to be easily removed from the skin when water is applied thereto.

This film containing the composition for topical application can be made using one of the above-described methods for the formation of multilayer shaped film products. It can also be made by casting and drying a layer of adhesive, and then casting the top layer on the bottom layer. The two layers can be attached to each other using any of the known methods of attachment (mechanical, chemical, dispersion, electrostatic, diffusion, etc.). In one embodiment, preferably both layers are water soluble such that the water in the non-adhesive outward facing layer will slightly dissolve the already dried adhesive skin contact layer, thus creating a certain diffusion adhesion at the interface of the two layers. In a second embodiment, both layers are cast in a wet-on-wet manner and mixing of the materials takes place at their interface, thus creating a bond by diffusion adhesion. The materials preferably share a common solvent and/or they are made to be mixed with each other so that they are mixed and combined with each other. It should be understood that the materials of the adhesive and non-adhesive layers (skin-contacting and outward-facing layers, respectively) may have a common solvent other than water, such as alcohol, so that the materials are bonded to each other.

For example, the skin contact layer preferably contains a hydrophilic film-forming polymer, a dissolving agent to dissolve other components in the film, a disintegration promoter, a thickener/texturing agent/texture modifier, a hygroscopic agent/wetting agent to retain skin moisture, a separation factor modifier/absorption aids. or penetration to introduce a hygroscopic agent into the skin, a plasticizer/primary adhesive agent for flexibility and softness, a solvent used for hydrocolloids, and to retain latent moisture and maintain the flexibility of the final product, as well as other auxiliary components or additives. The skin-contacting layer is preferably applied directly to the surface of the skin and has the properties to be used as the skin-contacting surface of the article. These properties include fast dissolution, stable adhesive strength, semi-occlusiveness and flexibility. The skin contact layer contains glucosamine hydrochloride and other ingredients of the topical formulation.

The outward-facing layer has properties that allow it to be used as a physical barrier, allowing it to remain free of dust, dirt, and foreign matter while the product is in place. These properties include fast dissolution, semi-occlusivity, flexibility and non-stickiness. Outward facing layer contains hydrophilic film-forming polymer, disintegration promoter, oil-in-water emulsifier, wax to limit water migration from skin-contact layer to topical layer, plasticizer for flexibility and softness, basic adhesive agent, solvent used for hydrocolloids , as well as in order to retain latent moisture and maintain the flexibility of the final product, as well as other auxiliary components or additives.

In a specific embodiment of the invention, the topical composition is contained in such a multilayer water-removable film. The film may have a thickness of, for example, up to about 2 mm. The film is placed on the skin by gluing the second bottom surface to the skin. Subsequently, the film is exposed to blue light with a peak wavelength of 400 nm to 460 nm using a light delivery device according to the invention. The film is held in place for a period of time, such as at least 15 minutes, or at least 30 minutes, or at least 3 hours, or at least 6 hours, whereby glucosamine hydrochloride can be transferred to the application site on the skin. Subsequently, the film is removed from the application site by applying water, whereby the film dissolves.

In a further embodiment of the foregoing, the lower skin-contacting layer further comprises an effective amount of an emulsifier to improve the transfer of glucosamine hydrochloride to the skin. In one embodiment, the emulsifier is a glycerol derivative. For example, the emulsifier may be selected from the group consisting of glycerides and glycerol fatty acid esters.

Light supply device

The light delivery device may comprise either a red light source or a near infrared light source, or both. In one embodiment, the light supply device supplies both red light and near infrared light.

As used herein, the term "red" light means light having a peak wavelength of about 600 to about 750 nm, preferably about 600 to about 700 nm. In one embodiment, the red light has a peak wavelength of about 633 nm.

As used herein, the term "near infrared" means light having a peak wavelength of about 750 to about 1000 nm, preferably about 800 to about 900 nm. In one embodiment, near infrared light has a peak wavelength of about 830.

The light delivery device may be of any shape or configuration, as long as it emits red light, near infrared light, or both. The light may be supplied continuously, in a pulsed manner, in a focused manner, in a diffuse manner, in multiple wavelengths, as coherent or non-coherent light within a desired range or at a desired wavelength.

In some preferred embodiments, only red, only near infrared, or only red and near infrared light is applied to the skin. That is, the light of other wavelengths is not supplied to the skin, either by filtering such other wavelengths, or in the absence of such wavelengths in the light provided by the light supply device.

In another such embodiment, only red light is supplied.

In a further embodiment, only near infrared light is supplied.

In a particularly preferred embodiment of the invention, both red light and near infrared light are supplied.

The light is preferably supplied at a low intensity. In one embodiment, the light delivery power is less than about 20 mW/cm ² . For example, light may be supplied at an intensity of from about 1 mW/cm ² to about 20 mW/cm ² . In another embodiment, the light intensity is less than about 1 mW/cm ² .

The blue light source may be, for example, one or more light emitting diodes (LEDs). The LEDs can be, for example, individual LED bulbs or strips with multiple LEDs.

The device may be in the form of a shaped mask, cover or hood for use on the face. In an alternative embodiment, the device may be in a form suitable for use on the body, in particular on the torso, such as the form of a skirt, jacket, etc. The device may be in the form of a patch having a round, oval, rectangular or other shape. Such a patch may also be irregularly shaped or shaped to fit a specific part of the face or body.

In one embodiment, the device comprises a lamp platform and a remote battery pack as described in US Pat. No. 8,771,328, the disclosure of which is incorporated herein by reference. The lamp platform for emitting lamps such as LEDs is located on a structure comprising a first wall to which the lamps are attached and a second wall closer to the skin and located at a distance from the first wall in which the lamps are recessed. The second wall includes a reflective surface facing the skin and a plurality of light holes substantially aligned with the LEDs on the first wall to propagate radiation from the lamps to the user. The lamps and their associated circuits are placed between the first and second walls so that the skin-facing reflective surface is relatively smooth and seamless. The number of lamps is kept as low as possible, as is the number of corresponding circuits, and other assembly materials are purposefully chosen to achieve a relatively low weight of the structure, resulting in increased comfort for the user during treatment sessions. The walls are plastic for flexible adjustment to the user. In particular, relative to the wearer's face, the walls have a concave configuration that can be adjusted from a neutral position to expand relative to the size of the wearer's head for a snug fit and secure fit on the wearer during use. The device is attached to the user's head by means of a frame including a frame for eyeglasses or goggles, including lenses to protect the user's eyes from lamp radiation. The adjustment capabilities of the embodiments are further enhanced in that the walls are rotatable relative to the support frame, and the frames may include retractable temples for selective adjustment to the user's head size. Thus, the device is attached to the user's head like a hands-free mask or the like. The power supply supplies power to the lamps and includes a remote battery pack, and may also include a control processor to count the number of uses of the device for the user, as well as to indicate the need to replace the device after a predetermined number of uses.

The platform is designed to be attached to the head by a variety of means: spectacle frames, straps, strings, straps, VELCRO Velcro, rotating handles or fasteners and buttons. While fixing the mask, it can be adjusted in height to cover the face from chin to forehead. It can also be adjusted in width to cover the sides of the face. In addition, once the platform has been folded/moved to cover the face area, the distance between the platform and the face can be adjusted to achieve the desired light intensity in relation to the user's skin surface. Thus, the effectiveness of light therapy can be maximized in three physical parameters.

The claimed controllability can be achieved through smart processing and sensor systems for increased flexibility/adjustability in the form of configurable power output, configurable wavelengths, priority zones, timers, and the like. The sensors of the sensor systems will allow the claimed embodiments to be able to assess the condition of the skin of the face and body of the patient using sensors to determine color, acne, damage, etc., as well as to plan "smart" treatment using more or less energy in priority areas. The claimed embodiments may be "smart" in terms of determining skin type, age, overall severity of problems, and may also be able to adjust treatment accordingly.

In another embodiment, the device comprises a therapeutic lamp platform for light emitting lamps, such as LEDs, located in a holdable dot applicator assembly as described in US 2016/0045758, the disclosure of which is incorporated herein by reference. Such a holdable point applicator assembly has a reflective surface facing the patient and a plurality of LEDs for delivering radiation from the lamps to the user. The lamps and associated circuitry are housed within an elongated structure that can be held.

In one embodiment, ultrasonic energy is also applied to the skin, in parallel or in series with the light. The ultrasonic energy can be supplied by a light source or a separate device.

In one embodiment, the light delivery device delivers both light and ultrasonic energy.

Production of hyaluronic acid

In accordance with the present invention, the combination of topical administration of glucosamine hydrochloride and exposure to red or near infrared light, or both, of the skin provides an unexpected increase in the level of hyaluronic acid produced by such skin. Such combinations have been found to provide a synergistic increase in the amount of hyaluronic acid produced by the skin compared to the amount obtained alone, either by topical administration of glusamine hydrochloride or by application of red and/or near infrared light.

In addition, combinations of red and/or near infrared light with other active ingredients, including other forms of glucosamine, do not provide a synergistic increase in skin hyaluronic acid production.

In one embodiment, the combination provides at least a 1.5 fold increase in hyaluronic acid production.

The level of production of hyaluronic acid can be measured using the following method.

Human dermal fibroblasts are maintained in a culture medium consisting of Dulbecco's Modified Eagle's Medium (DMEM), 10% fetal bovine serum, 50 units/ml penicillin, and 50 μg/ml streptomycin in a flask. Cells are seeded at 10,000 cells per well in a 96-well plate in phenol red-free Dulbecco's Modified Eagle's Medium (DMEM) plus 2% fetal bovine serum, 50 units/ml penicillin, and 50 μg/ml streptomycin for 24 hours before processing. Glucosamine HCl or other active substances were dissolved in 1x PBS to obtain a 10% solution and added to the medium at various concentrations and incubated for 48 hours. The culture medium is harvested 48 hours after treatment and HA (hyaluronic acid) secretion is measured using the Hyaluronan ELISA kit (Echelon, catalog number K-1200) according to the manufacturer's protocol. To evaluate the activity, the colorimetric change was measured at 405 nm.

The net HA recovery for each study treatment was calculated as the amount of HA recovered from each respective individual treatment minus the amount of HA recovered from the untreated sample. Then, the fold increase provided by the combination of light+activity treatments was calculated as the fold change in the level of pure HA produced by the combination of light and active treatment divided by the level of pure HA produced by light alone.

The topical composition and the light may be applied to the skin simultaneously or sequentially. When applied sequentially, composition and light can be applied in any order. When applied with ultrasonic energy, the composition, light, and ultrasonic energy can be applied simultaneously or in any order.

In one embodiment of the present invention, skin in need of treatment for signs of skin aging is treated by topical application to the skin of a composition containing up to about 2% by weight of glusamine hydrochloride and exposure of the skin to red light with a peak wavelength of about 600 nm to about 750 nm , near infrared light with a peak wavelength of about 750 nm to about 1000 nm, or both, using a light delivery device.

In another embodiment of the present invention, skin in need of hydration is treated by topical application to the skin of a composition containing up to about 2% by weight of glusamine hydrochloride and exposure of the skin to red light with a peak wavelength of about 600 nm to about 750 nm, near infrared light with a peak wavelength of about 750 nm to about 1000 nm, or both, using a light delivery device.

The following non-limiting examples further illustrate the invention.

Example 1

The activity of the following test treatments for the production of hyaluronic acid was compared using the in vitro method described above, using an untreated sample as a control: a) a combination of 633 nm red light and 830 nm infrared light (0.3 J/cm ² each), b ) combination of red light 633 nm and 830 nm infrared light (3 J/cm ² each), c) 0.02% glucosamine HCl in cell medium solution, d) 0.2% glucosamine HCl in cell medium solution, e) simultaneous application combination of red and infrared light (0.3 J/cm ² each) and 0.02% HCl glucosamine in cell medium solution and f) simultaneous application of a combination of red and infrared light (3 J/cm ² each) and 0.2% HCl glucosamine in cell medium solution.

The results are shown in Table 1.

TABLE 1 Treatment HA concentrations (ng/ml) Change in HA concentration compared to untreated sample (ng/mL) Multiplicity of change compared to treatment with light alone Without processing 551 0 - Red+near IR light (0.3 J/ ^cm2 each) 1412 +861 - Red+near IR light (3 J/ ^cm2 each) 1828 +1277 - 0.02% HCl glucosamine 543 -8 - 0.2% HCl glucosamine 999 +448 - Red+near IR light (0.3 J/ ^cm2 )+0.02% glucosamine HCl 2489 +1938 2.25 Red+near IR light (3 J/ ^cm2 )+0.02% glucosamine HCl 4379 +3828 2.99 Red+near IR light (0.3 J/ ^cm2 )+0.2% glucosamine HCl 2260 +1709 1.98 Red+near IR light (3 J/ ^cm2 )+0.2% glucosamine HCl 3873 +3322 2.60

Treatment with a combination of red and near infrared light and glucosamine HCl synergistically increased the production of hyaluronic acid in human skin fibroblasts compared to treatment with light alone.

Example 2

Using the same test method as in Example 1, the treatments presented in Table 2 were applied to human skin fibroblasts. Glucosamine phosphate was used instead of glucosamine hydrochloride.

Synergy was not observed.

table 2 Treatment HA concentrations (ng/ml) Change in HA concentration compared to untreated sample (ng/mL) Multiplicity of change compared to treatment with light alone Without processing 740 0 Red+near IR light (0.3 J/ ^cm2 each) 1572 832 0.02% glucosamine phosphate 689 -51 Red+near IR light (0.3 J/ ^cm2 )+0.02% glucosamine phosphate 1037 297 0.36

Example 3

Using the same test method as in Example 1, the treatments presented in Table 3 were applied to human skin fibroblasts. N-acetylglucosamine was used instead of glucosamine hydrochloride.

Synergy was not observed.

Table 3 Treatment HA concentrations (ng/ml) Change in HA concentration compared to untreated sample (ng/mL) Multiplicity of change compared to treatment with light alone Without processing 860 0 Red+near IR light (0.3 J/ ^cm2 each) 1784 924 0.02% N-acetylglucosamine 735 -125 Red+near IR light (0.3 J/ ^cm2 each)+0.02% N-acetylglucosamine 1878 1018 1.1

Example 4

Topical formulations containing glucosamine hydrochloride were prepared using the ingredients shown in Table 4 with pH values ranging from 4 to 5.5 by adjusting the amount of sodium hydroxide. Formulations having a pH greater than 5.5 were not physically stable on visual examination in appearance and color after 7 days at 60°C or after 30 days at 50°C.

Table 4 Name according to INCI % wt. Water 79.84 sodium hydrosulfite 0.1 Lemon acid 0.5 sodium citrate 0.13 Polyacrylate crosspolymer-6 0.8 Chlorphenesin 0.2 Cetearylolivat; Sorbitanolivat 0.5 Glycerol 8 polyisobutene; Polysorbate 20Polyacrylate-13 1.5 dimethicone; dimethicone crosspolymer; 1 Dimethicone 2.88 dimethicone; Dimethiconol 1.5 Ethylhexylglycerin; Phenoxyethanol 0.8 HCl glucosamine 1 Sodium hydroxide 0.25 Water 1 Total 100

Example 5

Two topical compositions for use in the claimed invention were prepared using the ingredients shown in Tables 5 and 6. The topical composition of Table 5 contained 0.1% by weight of sodium hydrogen sulfite. The topical composition of Table 6 did not contain sodium hydrosulfite.

When tested for physical stability using the method described in Example 4, the composition presented in Table 5 showed improved color and appearance compared to the composition from Table 6.

Table 5 Name according to INCI % wt. Water 79.97 sodium hydrosulfite 0.1 Lemon acid 0.5 Polyacrylate crosspolymer-6 0.8 Chlorphenesin 0.2 Cetearylolivat; Sorbitanolivat 0.5 Glycerol 8 polyisobutene; Polysorbate 20Polyacrylate-13 1.5 dimethicone; dimethicone crosspolymer; 1 Dimethicone 2.88 dimethicone; Dimethiconol 1.5 Ethylhexylglycerin; Phenoxyethanol 0.8 HCl glucosamine 1 Sodium hydroxide 0.25 Water 1 Total 100

Table 6 Name according to INCI % wt. Water 80.07 Lemon acid 0.5 Polyacrylate crosspolymer-6 0.8 Chlorphenesin 0.2 Cetearylolivat; Sorbitanolivat 0.5 Glycerol 8 polyisobutene; Polysorbate 20Polyacrylate-13 1.5 dimethicone; dimethicone crosspolymer; 1 Dimethicone 2.88 dimethicone; Dimethiconol 1.5 Ethylhexylglycerin; Phenoxyethanol 0.8 HCl glucosamine 1 Sodium hydroxide 0.25 Water 1 Total 100

The compositions shown in Table 7 were also prepared. Compositions A and B contained either BHT or tocopherol acetate, known antioxidants, instead of sodium hydrosulfite (Composition C). However, neither Composition A nor Composition B showed an improvement in physical stability over Composition C when tested in the manner described in Example 4.

Table 7 A B C Name according to INCI % wt. % wt. % wt. Water 80.62 80.69 80.64 Disodium salt EDTA 0.2 0.2 0.2 BGT 0.12 - - Tocopherol acetate - 0.05 - sodium hydrosulfite - - 0.1 Polyacrylate crosspolymer-6 0.8 0.8 0.8 Chlorphenesin 0.2 0.2 0.2 Cetearylolivat; Sorbitanolivat 0.5 0.5 0.5 Glycerol 8 8 8 polyisobutene; Polysorbate 20Polyacrylate-13 1.5 1.5 1.5 dimethicone; dimethicone crosspolymer; 1 1 1 Dimethicone 3.5 3.5 3.5 dimethicone; Dimethiconol 1.5 1.5 1.5 Ethylhexylglycerin; Phenoxyethanol 0.8 0.8 0.8 HCl glucosamine 1 1 1 Sodium hydroxide 0.13 0.13 0.13 Water 0.13 0.13 0.13 Total 100 100 100

Claims (6)

1. A method for increasing the production of hyaluronic acid in human skin fibroblasts, which includes topical application of a topical composition to human skin and simultaneous exposure of said skin to red light with a peak wavelength of 633 nm and near infrared light with a peak wavelength of 830 nm, using a device supply of light at a light intensity of 0.3 J/cm ² or 3 J/cm ² , characterized in that the topical composition contains 0.02 mass percent of glucosamine hydrochloride and has a pH of 3.0 to 5.5. 2. The method of claim 1 further comprising exposing said skin to ultrasonic energy. 3. Method according to claim 2, characterized in that the light supply device supplies both light and ultrasonic energy. 4. A method for increasing the production of hyaluronic acid in human skin fibroblasts, including local application of a topical composition to human skin and simultaneous exposure of said skin to red light with a peak wavelength of 633 nm and near infrared light with a peak wavelength of 830 nm, using a device supply of light at a light intensity of 0.3 J/cm ² or 3 J/cm ² , characterized in that the topical composition contains 0.2 mass percent of glucosamine hydrochloride and has a pH of 3.0 to 5.5. 5. The method of claim 4, further comprising exposing said skin to ultrasonic energy. 6. Method according to claim 5, characterized in that the light supply device supplies both light and ultrasonic energy.