Use of caprylic and capric triglycerides for treating diseases or conditions mediated by filaggrin or collagen deficiency

Abstract

The present invention relates to the use of caprylic and capric triglycerides, a combination of caprylic and capric triglycerides with melatonin or a derivative thereof, or a composition containing caprylic and capric triglycerides alone or in combination with melatonin or a derivative thereof, for treating diseases or conditions mediated by filaggrin or collagen deficiency.

Description

[0001] Related Applications

[0002] This application claims the benefit of European patent application EP19382169.1 filed on March 6, 2019. Technical Field

[0003] The present invention relates to the use of caprylic and capric triglycerides, a combination of caprylic and capric triglycerides and melatonin or a derivative thereof, or a composition containing them for treating diseases or conditions mediated by a deficiency of filaggrin or collagen. Background Art

[0004] Disorders of the matrix components of fibroblasts and keratinocytes have been identified as one of the main causes of common skin disorders as well as some connective tissue disorders. Deficiencies in the amount of filaggrin and / or collagen may be caused by abnormal production of these proteins or by increased degradation of these proteins.

[0005] On the one hand, filaggrin is a silk-related protein that binds to keratin fibers in epithelial cells that play a key role in the barrier function of the epidermis. The protein is also a major component of the protein-lipid cornified envelope of the epidermis, which is important for water permeability and blocking the entry of microorganisms and allergens. Therefore, filaggrin is crucial for the regulation of epidermal homeostasis.

[0006] Individuals with a deficiency in the amount of filaggrin are strongly prone to skin diseases such as dry skin, ichthyosis vulgaris and / or eczema. These skin diseases are characterized by excessive lines, keratosis pilaris, itchy, scaly and often inflamed skin. Unfortunately, there is no cure for filaggrin deficiency or taking filaggrin supplements. Only some measures attempt to restore the amount of filaggrin in the skin. Some of these measures involve avoiding soaps, detergents, shampoos and scrubs and / or increasing the use of emollients.

[0007] On the other hand, collagen is a protein found in the skin that gives the skin a plump and smooth appearance. In addition, it also maintains internal organs, muscles, tendons, cartilage, and is also present in teeth. Collagen accounts for 25% of the total amount of protein in the body. There are about 20 different types of collagen in the body. Each group of collagen plays an important role in many functions of the body, such as forming and maintaining internal organs. In particular, type III collagen is a fibrous collagen that consists of only one collagen α chain and is secreted by fibroblasts and other mesenchymal cell types. In particular, type III collagen is a major player in various inflammatory-related conditions, such as lung injury, viral and non-viral liver disease, renal fibrosis, hernia and vascular disorders. In addition, type III collagen is the main component of the interstitial matrix together with type I collagen.

[0008] Collagen is essential for having healthy and smooth skin. The skin layer responsible for wrinkles is the dermis, which is composed of blood vessels, sebaceous glands and hair follicles. Collagen is necessary for the support and elasticity of the dermis. Collagen production naturally decreases with age, causing the appearance of wrinkles, scarring and sagging skin in the skin. When the deficiency of collagen is in the muscles, muscle pain and soreness are experienced; while if the collagen deficiency is in the cartilage, it causes joint pain. In addition, diseases or conditions mediated by collagen degeneration also affect the skin, muscles and / or cartilage. This collagen degeneration can be caused by environmental factors (such as sun exposure) or by some connective tissue diseases (such as rheumatic fever, rheumatoid arthritis and lupus, etc.).

[0009] When collagen deficiency is affecting the skin, it can be treated with collagen injections. Collagen injection treatment involves injecting purified animal / cadaver-derived collagen under the skin of the affected area. Meanwhile, when collagen deficiency affects organs, then the treatment involves taking collagen supplements (available in liquid and pill form). In addition, collagen supplements can also prevent collagen deficiency from developing them. However, prescription drugs used for collagen supplements may have side effects derived from their origin (animal or cadaver-derived collagen), such as allergic reactions.

[0010] Therefore, based on what is known in the prior art, there remains a need to develop new compounds for treating diseases or conditions mediated by filaggrin or collagen deficiency. Summary of the invention

[0011] The inventors have discovered that caprylic and capric triglycerides result in increased expression of the matrix proteins filaggrin and collagen and that, therefore, topical administration of specific amounts of caprylic and capric triglycerides is useful as an active ingredient for treating diseases or conditions mediated by filaggrin or collagen deficiency.

[0012] Furthermore, the inventors have also found that combinations of caprylic and capric triglycerides with other active ingredients such as melatonin or its derivatives are also useful as active ingredients for treating diseases or conditions mediated by filaggrin or collagen deficiency.

[0013] Thus, a first aspect of the present invention relates to caprylic and capric triglycerides for use in treating a disease or condition mediated by filaggrin or collagen deficiency, wherein the treatment comprises topical application of a therapeutically effective amount of caprylic and capric triglycerides.

[0014] In addition, a second aspect of the present invention refers to a topical composition for use in treating diseases or conditions mediated by filaggrin or collagen deficiency, wherein the treatment comprises topical application of the composition, which comprises an effective amount of caprylic and capric triglycerides ranging from 0.1 wt % to 70 wt % of the total weight of the composition, and one or more suitable topically acceptable excipients or carriers.

[0015] Also part of the invention is a combination of caprylic and capric triglycerides and melatonin or a derivative thereof, or a composition containing them, for use in treating a disease or condition mediated by filaggrin or collagen deficiency. DETAILED DESCRIPTION

[0016] Unless otherwise stated, all terms used herein in this application should be understood with their common meanings known in the art. Other more specific definitions of certain terms as used in this application are described below, and are intended to be uniformly applied throughout the specification and claims unless otherwise expressly stated definitions provide broader definitions.

[0017] For the purpose of the present invention, any range given includes both the lower and upper endpoints of the range. Unless otherwise specified, given ranges (such as temperature, time, etc.) should be considered approximate.

[0018] The terms "weight percent (%)" or "wt%" are used interchangeably and they refer to the percentage of each ingredient relative to the total weight of the composition.

[0019] As mentioned above, the first aspect of the present invention is directed to the use of a therapeutically effective amount of caprylic and capric triglycerides for treating a disease or condition mediated by filaggrin or collagen deficiency.

[0020] As used herein, the term "therapeutically effective amount" refers to an amount of active ingredient (e.g., caprylic and capric triglycerides) that, when administered, is sufficient to prevent the development of the disease to be addressed or to alleviate to some extent one or more symptoms of the disease. The specific dose of active ingredient administered according to the present invention will be determined by the particular circumstances surrounding the case, including the compound administered, the route of administration, the specific condition being treated, and similar considerations.

[0021] For the purposes of the present invention, the terms "caprylic and capric triglycerides", "caprylic / capric triglycerides" and the abbreviation "CCT" have the same meaning and they are used interchangeably. In particular, CCT is an oily liquid made from mixed esters (composed of caprylic and capric fatty acids) obtained by esterification of glycerol (vegetable sugar) with a mixture of caprylic (C:8) and capric (C:10) fatty acids from coconut oil or palm kernel oil. Caprylic / capric triglycerides are commercially available under the trademark Miglyol 812, among others.

[0022] In one embodiment, the caprylic and capric triglycerides used according to the invention are caprylic and capric triglycerides, wherein the disease or disorder is mediated by filaggrin deficiency, in particular selected from the group consisting of psoriasis, atopic dermatitis and ichthyosis vulgaris.

[0023] In one embodiment, the caprylic and capric triglycerides used according to the invention are caprylic and capric triglycerides, wherein the disease or disorder is mediated by collagen deficiency, in particular selected from the group consisting of skin aging and skin photoaging.

[0024] As shown in the examples of the present invention, caprylic acid and capric triglycerides promote the expression (production) of filaggrin and collagen, and therefore, they can be used to treat diseases or conditions mediated by filaggrin or collagen deficiency. Therefore, this aspect can also be clearly expressed as the use of caprylic acid and capric triglycerides as defined above for the preparation of a medicament for treating a disease or condition mediated by filaggrin or collagen deficiency, wherein the treatment comprises topical application of a therapeutically effective amount of caprylic acid and capric triglycerides. Also related is a method for treating a mammal suffering from or susceptible to a disease or condition mediated by filaggrin or collagen deficiency, wherein the method comprises administering to the mammal a therapeutically effective amount of caprylic acid and capric triglycerides, and one or more pharmaceutically acceptable excipients or carriers.

[0025] In one embodiment, the caprylic and capric triglycerides used according to the present invention are such caprylic and capric triglycerides, wherein the treatment comprises topical application of caprylic and capric triglycerides in combination with melatonin or a derivative thereof. In one embodiment, the caprylic and capric triglycerides used according to the present invention are such caprylic and capric triglycerides, wherein the treatment comprises topical application of caprylic and capric triglycerides in combination with a therapeutically effective amount of melatonin or a derivative thereof.

[0026] For the purposes of the present invention, the term "melatonin" is the nonproprietary name for "N-acetyl-5-methoxytryptamine" having the following formula, having CAS Registry Number 73-31-4:

[0027]

[0028] The term "melatonin and its derivatives" refers to compounds having the following formula:

[0029]

[0030] wherein each of R1 and R2 is independently selected from the group consisting of H and halogen. The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0031] As described above, the second aspect of the present invention refers to a topical composition for use in the treatment of diseases or conditions mediated by filaggrin or collagen deficiency, wherein: the treatment comprises topical application of the composition, which comprises an effective amount of caprylic and capric triglycerides ranging from 0.1 wt % to 70 wt % of the total weight of the composition, and one or more suitable topically acceptable excipients or carriers.

[0032] In one embodiment, the composition for use in treating a disease or condition mediated by filaggrin or collagen deficiency is a composition wherein the therapeutically effective amount of caprylic and capric triglycerides is such that the therapeutically effective amount of caprylic and capric triglycerides is 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 0%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69 and 70%.

[0033] In one embodiment, the composition for use in the treatment of a disease or condition mediated by filaggrin or collagen deficiency is a composition wherein the treatment comprises topical application of the composition comprising: 0.1% to 70% by weight of caprylic and capric triglycerides and a therapeutically effective amount of melatonin or a derivative thereof as defined above, in particular 0.004% to 12% by weight of melatonin or a derivative thereof; and one or more acceptable excipients or carriers.

[0034] The term "topical composition" refers to a composition suitable for "topical application" thereof. The term "topical application" refers to application to the skin, hair, ears, mucous membranes, rectal application and nasal application, as well as application to the teeth or gums in the oral cavity.

[0035] All embodiments disclosed above in relation to diseases or conditions mediated by filaggrin or collagen deficiency in relation to the first aspect of the invention also apply to the composition of the second aspect of the invention.

[0036] The term "suitable topically acceptable" refers to excipients or carriers that are suitable for preparing a composition suitable for topical application.

[0037] The topical compositions of the present invention may be formulated in a number of forms including, but not limited to, solutions, aerosol and non-aerosol sprays, shaving creams, powders, mousses, lotions, gels, sticks, ointments, pastes, creams, shampoos, shower gels, body washes, or face washes.

[0038] The topical compositions of the present invention can be prepared according to methods well known in the art. Suitable excipients and / or carriers and their amounts can be readily determined by those skilled in the art depending on the type of formulation being prepared.

[0039] In one embodiment, the topical composition for use of the present invention is a topical composition wherein a suitable topical excipient or carrier is selected from the group consisting of a skin barrier restoration agent, a water absorbent, an emollient, an emulsifier, a surfactant, a thickener, a humectant, a pH adjuster, an antioxidant, a preservative, a vehicle, a chelating agent, an absorbent, and a mixture thereof.

[0040] As used herein, the terms "moisturizer" or "moisturizing agent" or "moisturizing agent" are used interchangeably to refer to materials that increase the moisture content of the skin and help keep it soft and smooth. Examples of suitable topical water absorbents include, but are not limited to, dimethiconol, glycine, hyaluronic acid, sodium hyaluronate crosspolymer, betaine, dimethylsilanol hyaluronate, magnesium stearate, maltitol, maltose, pyrrolidone carboxylic acid (PCA), manganese PCA, sodium PCA, mannitol, trehalose, trilactin, glucose, glutamic acid, hydrolyzed caesalpinia spinosa gum, caesalpinia spinosa gum, prunus persica extract, prunus serotina extract, echinacea angustifolia extract, echinacea purpurea extract, methyl gluceth, hydrolyzed wheat protein, erythritol, aluminum stearoyl glutamate, copper acetylmethionate, or ditridecyl dimmer dilinoleate. The amount of water absorbent in the composition of the present invention may range from 0,01% to 20%.

[0041] The term "skin barrier restoration agent" refers to a material whose composition and / or structure is similar to the skin barrier so as to repair its defects. Examples of suitable topical skin barrier restoration agents include, but are not limited to, ceramides, cholesterol, fatty acids, and precursors of these lipids (including cerebrosides, sphingoid bases (such as phytosphingosine or sphingosine)), or phospholipids (including phosphatidylcholine) and agents that promote the synthesis of epidermal lipids (such as niacinamide, urea, dexpanthenol, and α-hydroxy acids including lactic acid), etc. The amount of the skin barrier restoration agent in the composition of the present invention may be 0.1% to 20%.

[0042] The term "emollient" refers to softening and smoothing the skin to correct dry skin and desquamation, thereby lubricating the skin surface, promoting skin moisture retention and changing the material of the product texture. The term "emollient" includes hydrophilic emollients and lipophilic emollients. The term "hydrophilic emollient" refers to an emollient soluble in water, such as glycerol, sorbitol and propylene glycol. The term "lipophilic emollient" includes water-insoluble. The example of suitable topical emollients includes but is not limited to octyl hydroxystearate, lanolin, caprylic / capric triglyceride, palmitic acid cetyl ester, octyldodecanol, cetyl alcohol, isostearic acid isopropyl ester, glyceryl dilaurate, isopropyl myristate, palmityl alcohol, dimethicone, squalane, plukenetia volubilis seed oil, shea butter (butyrospermum parkii) butter, sucrose cocoate or its mixture. Amounts of emollients in the compositions of the present invention may range from 0.1% to 35%.

[0043] The term "humectant" refers to a hygroscopic material that attracts water molecules from the surrounding environment by absorption or adsorption, thereby preventing the skin from losing moisture. Examples of suitable topical humectants include, but are not limited to, glycerol, diglycerol, ethylhexylglycerol, glucose, honey, lactic acid, polyethylene glycol, propylene glycol, sorbitol, sucrose or threalose. The amount of humectant in the composition of the present invention may be 0.1% to 10%.

[0044] As used herein, the terms "thickening agent" or "thickener" or "viscosity agent" interchangeably refer to a material that increases its viscosity without substantially changing its other properties. Examples of suitable topical thickeners include, but are not limited to, cellulose or its derivatives, such as hydroxypropyl methylcellulose, polyethylene glycol, microcrystalline cellulose, cetearyl alcohol, alginates, branched polysaccharides, fumed silica, xanthan gum, carbomers, and polyacrylates. The amount of thickener in the composition of the present invention may be from 0.1% to 3%.

[0045] As used herein, the terms "emulsifying agent" or "emulsifier" interchangeably refer to a material that reduces surface tension, thereby facilitating the formation of a homogenous mixture of immiscible liquids by altering the interfacial tension. Emulsifiers stabilize emulsions by increasing the kinetic stability of the emulsion.

[0046] The term "surfactant" refers to a material that reduces the surface tension of a liquid and the interfacial tension between two liquids, making it easier to spread. Surfactants have a hydrophilic head that attracts water molecules and a hydrophobic tail that repels water and simultaneously attaches itself to the grease in the dirt. These opposing forces release the dirt and suspend it in water, thus having the ability to remove it from surfaces such as human skin, textiles, and other solids when the surfactant is dissolved in water.

[0047] The topical composition used is preferably formulated as an emulsion. An emulsion is a dispersed system comprising at least two immiscible phases, one phase being dispersed as droplets in the other phase. The above-mentioned emulsifiers are included to improve stability. When water is the dispersed phase and oil is the dispersion medium, the emulsion is referred to as a water-in-oil emulsion (w / o). When oil is dispersed as droplets in the aqueous phase, the emulsion is referred to as an oil-in-water emulsion (o / w). Other types of emulsions known in the art are multiple emulsions, such as water-in-oil-in-water emulsions (w / o / w); GELTRAP emulsions, in which the inner aqueous phase is gelled and it is covered by an oil phase; and SWOP emulsions, also known as inverse emulsions. The emulsion used is preferably an oil-in-water emulsion. Preferably, the emulsion used for use in the sense of the present invention is compatible with creams and lotions.

[0048] Another topical composition for use is preferably formulated as a "surfactant base". A surfactant base is a blend of at least two surfactants. Surfactants are commonly used in cleaning products to break down colorants and to hold soils in aqueous solution to prevent them from redepositing on surfaces. Surfactants disperse soils that are normally insoluble in water, thereby making them dispersible in water and removable with the wash water. The above-mentioned surfactants are included in order to reduce surface tension. Preferably, the surfactant base for use in the sense of the present invention is compatible with shampoos, shower gels and body or facial washes.

[0049] The term "antioxidant" refers to a material that slows down or prevents oxidation of other molecules. Antioxidants include free radical scavengers and reducing agents. Examples of suitable antioxidants include, but are not limited to, free radical scavengers or reducing agents, such as acetylcysteine, ascorbic acid, ascorbyl palmitate, butylated hydroxytoluene, green tea extract, caffeic acid, cysteine, tocopherol, ubiquinone, carnosine, propyl gallate, butylated hydroxytoluene (BHT) and mixtures thereof. The amount of the antioxidant in the composition of the present invention can be 0.1% to 20%.

[0050] The term "pH adjusting" agent refers to an acid or base that can be used to adjust the pH of the finished product to a desired level without affecting the stability of the solution. Examples of suitable topical pH adjusting agents include, but are not limited to, acetic acid, lactic acid, citric acid, ethanolamine, formic acid, oxalic acid, potassium hydroxide, sodium hydroxide, triethanolamine, or mixtures thereof. The amount of pH adjusting agent in the composition of the present invention may be 0.01% to 3%.

[0051] The term "preservative" refers to a material that prevents or reduces or slows the growth of microorganisms, provided that the stability of the solution is not affected. Examples of suitable preservatives include, but are not limited to, benzoic acid, butyl paraben, ethyl paraben, propyl paraben, methyl paraben, sorbic acid, potassium sorbate, sodium benzoate, phenoxyethanol, triclosan, or a mixture thereof. The amount of preservative in the composition of the present invention may be 0.01% to 1.5%.

[0052] The term "chelating agent" refers to a material capable of coordinating or binding metal ions such as calcium, magnesium, iron and manganese metal ions. The amount of chelating agent in the composition of the present invention may range from 0.001% to 0.1%.

[0053] The term "absorbent" refers to a material that is capable of interacting with and retaining a compound that has an affinity for the absorbent. The term absorbent may also be any material that can absorb moisture from the surrounding atmosphere or otherwise remove moisture, or any material that can absorb or otherwise remove other compounds from the atmosphere, such as but not limited to oxygen, carbon dioxide, carbon monoxide, and amine complexes. In this article, the term absorbent may be used interchangeably with the term dehydrating agent, desiccant, or adsorbent. Non-limiting examples of absorbents include silica gel, desiccant clay, molecular sieves, zeolites, or combinations thereof. The amount of absorbent in the composition of the present invention may be 0.1% to 5%.

[0054] The above composition also includes a vehicle. Examples of vehicles include, but are not limited to, water, propylene glycol, butylene glycol, ethanol, isopropanol or silicone. Preferably, the vehicle is water.

[0055] Additionally, the compositions of the present invention may contain other ingredients such as fragrances, flavors, colorants, and other components known in the art for use in topical formulations.

[0056] In one embodiment, the topical composition for use of the second aspect of the invention is a topical composition wherein the composition comprises one or more additional active ingredients; in particular one or more additional active ingredients selected from the group consisting of cannabinoids, bakuchiol, vitamins or derivatives thereof, peptides, alpha hydroxy acids, alpha amino acids, sunscreen actives and mixtures thereof.

[0057] In one embodiment, the topical composition further comprises as additional active ingredients one or more cannabinoids; in particular selected from the group consisting of palmitoylethanolamide and analogs and derivatives thereof.

[0058] In one embodiment, the topical composition further comprises as additional pharmaceutically active ingredients one or more vitamins or derivatives thereof; in particular, they are selected from the group consisting of vitamin C and its esters, B group vitamins and their derivatives such as vitamin B3 (niacinamide). In one embodiment, the topical composition further comprises as additional pharmaceutically active ingredients one or more vitamins or derivatives thereof in an amount of 0.5% to 30% by weight of the composition.

[0059] In one embodiment, the topical composition further comprises one or more vitamin C esters selected from the group consisting of ascorbyl tetraisopalmitate, ascorbyl palmitate, ascorbyl stearate, ascorbyl linoleate and mixtures thereof; in particular ascorbyl tetraisopalmitate. In one embodiment, the topical composition further comprises one or more vitamin C esters as defined above in an amount of 1% to 20% by weight of the composition.

[0060] In one embodiment, the topical composition further comprises a B group vitamin. In one embodiment, the topical composition further comprises niacinamide. In one embodiment, the topical composition further comprises niacinamide in an amount of 0.5% to 6% by weight of the composition. For the purposes of the present invention, the terms "niacinamide", "nicotinamide", "nicotinic acid amide", "pyridine-3-carboxylic acid amide", "vitamin B3" and "vitamin PP" have the same meaning and are used interchangeably. They refer to the non-proprietary names of compounds having CAS registration number 98-92-0 and the following formula:

[0061]

[0062] In one embodiment, the topical composition further comprises bakuchiol; in particular, in an amount of 0.1% to 1% by weight of the composition. For the purposes of the present invention, the term "bakuchiol" is a nonproprietary name for a natural meroterpene isolated from Psoralea corylifolia, having CAS Registry Number 10309-37-2 and having the following formula:

[0063]

[0064] In one embodiment, the topical composition further comprises one or more peptides as additional active ingredients; in particular, selected from the group consisting of carnosine, palmitoyl oligopeptide, palmitoyl tetrapeptide-7, tetradecylaminobutyryl valylaminobutyric acid uron trifluoroacetate and other signal peptides, carrier peptides and neurotransmitter peptides. In one embodiment, the topical composition further comprises one or more peptides as additional pharmaceutically active ingredients in an amount of 1% to 11% by weight of the composition.

[0065] For the purposes of the present invention, the terms "carnosine" and "L-carnosine" have the same meaning, and they are used interchangeably. These terms are nonproprietary names for β-alanyl-L-histidine having the following formula, having CAS Registry Number 305-84-0:

[0066]

[0067] In one embodiment, the topical composition further comprises carnosine; particularly in an amount of 0.01% to 5% by weight of the composition.

[0068] In one embodiment, the topical composition further comprises as additional active ingredients one or more alpha hydroxy acids; in particular chosen from the group consisting of glycolic acid, lactic acid and citric acid.

[0069] In one embodiment, the topical composition further comprises as additional active ingredients one or more alpha amino acids; in particular selected from the group consisting of: betaine, 1% and 5% by weight of the composition; in particular betaine. For the purposes of the present invention, the term betaine is the nonproprietary name for 2-trimethylammonioacetate having CAS registration number 107-43-7 and having the following formula:

[0070]

[0071] In one embodiment, the topical composition further comprises one or more sunscreen active agents as additional pharmaceutical active ingredients. The term "sunscreen active agent" as used herein refers to such single or combined materials that are considered as acceptable materials as active sunscreen ingredients based on their ability to absorb, scatter or reflect ultraviolet (UV) radiation. Such compounds are generally described as UVA, UVB or UVA / UVB active agents. In particular, "sunscreen organic active agents" refer to such single or combined organic compounds that are considered as acceptable materials as active sunscreen ingredients based on their ability to primarily absorb ultraviolet (UV) radiation. Such compounds are generally described as UVA, UVB or UVA / UVB active agents.

[0072] In one embodiment, the topical composition for use of the second aspect of the invention is a topical composition comprising:

[0073] 55 to 70% by weight caprylic and capric triglycerides;

[0074] 0.004 wt % to 1 wt % of melatonin or a derivative thereof as defined in claim 3;

[0075] 0.1 wt % to 1 wt % bakuchiol; and

[0076] 1 to 20% by weight of vitamin C or its derivatives;

[0077] The sum of the ingredients is 100% by weight.

[0078] In one embodiment, the topical composition for use of the second aspect of the invention is a topical composition comprising:

[0079] 55 to 70% by weight caprylic and capric triglycerides;

[0080] 0.004 wt % to 1 wt % of melatonin or a derivative thereof as defined in the present invention;

[0081] 0.1 wt % to 1 wt % bakuchiol;

[0082] 1 to 11 wt % of vitamin C or its derivatives; and

[0083] 20 to 30 wt. % emollient;

[0084] The sum of the ingredients is 100% by weight.

[0085] In one embodiment, the topical composition for use of the second aspect of the invention is a topical composition wherein the emollient is selected from the group consisting of isodecyl neopentanoate, dimethicone, hydrogenated polyisobutene, octyldodecanol and mixtures thereof.

[0086] As mentioned above, the second aspect of the present invention refers to a pharmaceutical topical composition for use in the treatment of diseases or conditions mediated by a deficiency of filaggrin or collagen, wherein: the treatment comprises topical application of a pharmaceutical composition comprising 0.1% to 70% by weight of a therapeutically effective amount of caprylic and capric triglycerides, and one or more pharmaceutically acceptable excipients or carriers. The composition comprising caprylic and capric triglycerides of the second aspect of the present invention promotes the expression (production) of filaggrin and collagen. This aspect can also be explicitly expressed as the use of a topical pharmaceutical composition as defined above for the preparation of a medicament for the prevention and / or treatment of a disease or condition mediated by a deficiency of filaggrin or collagen, wherein the treatment comprises topical application of a pharmaceutical composition of the present invention comprising 0.1% to 70% by weight of a therapeutically effective amount of caprylic and capric triglycerides. It also relates to a method for treating a mammal suffering from or susceptible to a disease or condition mediated by a deficiency of filaggrin or collagen, wherein the method comprises administering to the mammal a therapeutically effective amount of a topical pharmaceutical composition of the present invention.

[0087] Throughout the specification and claims, the word "comprising" and variations of the word are not intended to exclude other technical features, additives, components or steps. In addition, the word "comprising" covers the situation of "consisting of..." Other objects, advantages and features of the present invention will become apparent to those skilled in the art after examining the specification, or can be learned through the practice of the present invention. The following examples are provided by way of illustration, and they are not intended to limit the present invention. In addition, the present invention covers all possible combinations of specific and preferred embodiments described herein.

[0088] Example

[0089] 1. Composition of the present invention

[0090] 1.1. Example 1 - Nighttime Emulsion

[0091] A. Composition

[0092] The emulsion composition is as follows

[0093]

[0094]

[0095]

[0096] In the above composition, the amount of caprylic and capric triglycerides was 2 wt%, the amount of carnosine was 0.5 wt%, the amount of niacinamide was 3 wt%, the amount of melatonin was 0.05 wt% and the amount of betaine was 1 wt%.

[0097] B. Preparation process

[0098] A night cream having the composition indicated in the following table was prepared according to a process comprising the following steps:

[0099] B.1. Phase preparation

[0100] Water phase (%) (1) : Add the components from phase (1) successively in the main container under stirring until you have a homogeneous solution.

[0101] Oil phase (2): In a secondary vessel, add the components from phase (2) and dissolve them.

[0102] Phase (3): In an auxiliary vessel, add the components from phase (3) one after the other while stirring until a homogeneous mixture exists.

[0103] B.2. Process for making emulsions:

[0104] Step 1: adding phase (2) to phase (1) and then mixing the resulting mixture until having an emulsion; and

[0105] Step 2: Phase (3) is added to the resulting emulsion obtained in step 1 to obtain the final emulsion.

[0106] 1.2. Example 2

[0107] A. Composition

[0108]

[0109]

[0110] In the above composition, the amount of caprylic and capric triglycerides is 55 wt %, the amount of melatonin is 0.05 wt %, the amount of bakuchiol is 0.3 wt %, and the amount of the vitamin C derivative is 8 wt %.

[0111] B. Preparation process

[0112] Components 0 to 10 were added one by one with stirring until a homogeneous mixture was obtained.

[0113] 2. Determination of Matrix Protein

[0114] 2.1. Sample

[0115] -Normal human dermal fibroblast growth supplement was purchased from PAN Biotech.

[0116] - Cell culture medium including Dulbecco's modified Eagle's medium (DMEM, fetal bovine serum (FBS) and penicillin-streptomycin) was obtained from Gibco BRL.

[0117] -Normal human keratinocyte growth supplement was purchased from CELLnTech.

[0118] For the determination of collagen III in fibroblast cultures:

[0119] - Fibroblasts treated with 500 μl of caprylic / capric triglyceride at concentrations of 0.1%, 0.2%, 1% and 2% (expressed in g / 100 mL).

[0120] - Blank: fibroblasts P8-9

[0121] For determination of filaggrin in keratinocyte cultures:

[0122] - Keratinocytes treated with 500 μl of caprylic / capric triglyceride at concentrations of 0.1%, 0.2%, 1% and 2% (expressed in g / 100 mL).

[0123] -Blank: Keratinocytes

[0124] The amount of active ingredient (e.g. caprylic and capric triglycerides) used in the in vitro assays for measuring collagen III in fibroblast cultures and filaggrin in keratinocyte cultures is equivalent to the amount of active ingredient that reaches fibroblasts and keratinocytes after topical application of the composition of the invention to the skin.

[0125] 2.2. Equipment

[0126] Nikon Ti-S microscope (metamorph).

[0127] Incucyte (ESSEN BioScience).

[0128] Antibodies

[0129] -Purified freeze-dried antibody against human type III collagen; Ref: 20311 (novotec)

[0130] - Anti-filagrin antibody; Reference: PAJ103hu01 (cloud-cloud)

[0131] 2.4. Methods

[0132] -Normal human dermal fibroblast growth supplement was purchased from PAN Biotech.

[0133] - Cell culture medium including Dulbecco's Modified Eagle's Medium (DMEM, fetal bovine serum (FBS) and penicillin-streptomycin) was obtained from Gibco BRL.

[0134] -Normal human keratinocyte growth supplement was purchased from CELLnTech.

[0135] Cell culture

[0136] Fibroblasts

[0137] - Culture: Primary human dermal facial fibroblasts (HDFs) were isolated from human dermal facial tissue removed at the time of cosmetic surgery in a woman (45 years old) and used at passages 2 to 15. HDFs were maintained in DMEM containing 10% FBS and 1% penicillin-streptomycin.

[0138] - Human fibroblasts: Facial epidermal fibroblasts from a 40-year-old patient.

[0139] Keratinocytes

[0140] - Culture: Primary human epidermal adult keratinocytes (HEK) isolated from human epidermal tissue were purchased from CELLnTecadvanced cell systems. HEK were maintained in CnT-basal medium supplemented with Cnt-57-S (CELLnTEC). Cells were maintained in a humidified chamber at 5% CO2 and 37°C. The culture medium was changed every 4 days.

[0141] - Human keratinocytes: epidermal keratinocyte progenitor cells, pooled: (HPEKp; CellnTec).

[0142] Immunostaining

[0143] For immunostaining, the culture cells in the wells were washed with PBS and fixed with 4% paraformaldehyde for 10 min. After washing with PBS, the fixed cells were permeabilized with 0.2% Triton-X100 in PBS for 10 min. After washing twice with PBS, the cells were blocked with 1% BSA+0.1% Tween 20 in PBS for 60 min at 37°C. The cells were incubated with the primary antibody overnight at 37°C in blocking buffer. After washing, the following secondary antibodies were applied: Alexa Fluor 488 goat anti-mouse immunoglobulin G (IgG) (Molecular Probes) and Alexa Fluor 488 goat anti-rabbit IgG (Molecular Probes). The cells were incubated with the secondary antibodies at room temperature in blocking buffer for 2 hours. After washing with PBS, the cells were incubated with DAPI at room temperature for 10 min. Fluorescence images were obtained using a Nikon Ti-S microscope with a band filter (DAPI / GFP).

[0144] 2.7. Determination of collagen III in fibroblast culture

[0145] The following table shows that the production of collagen III in fibroblasts was increased by using CCT. The amount of collagen III expressed increased by 1.1, 1.8, 2.3 and 2.5 times with increasing concentrations of CCT as described in the following table, where the amount of CCT is expressed as CCT grams / 100 mL:

[0146] CCT(%) Expression of collagen III in fibroblasts 0 (blank) 57558,6 0.1 62627,1 0.20 102986,8 1 130587,6 2 141063,6

[0147] As shown in the above results, CCT increases the production of collagen, particularly collagen III, in fibroblasts. This is advantageous because CCT can be used to improve or treat diseases or conditions mediated by collagen deficiency caused by a decrease in collagen production or by an increase in collagen degeneration.

[0148] 2.8. Determination of filaggrin in keratinocyte cultures

[0149] The following table shows that the production of filaggrin in fibroblasts was increased by using CCT. The amount of filaggrin expressed increased by 1.7 and 2.8 fold with increasing concentrations of CCT as described in the following table, and the amount of CCT is expressed as CCT grams / 100 mL:

[0150] CCT(%) Expression of filaggrin in keratinocytes 0 (blank) 38795,3 1.00 65175,8 10 108008,1

[0151] As shown in the above results, CCT increases the production of filaggrin in fibroblasts. This is advantageous because, since filaggrin plays a key role in maintaining an effective skin barrier against environmental conditions, CCT can be used as a skin restorative for enhancing / restoring the function and health of the skin. In particular, CCT can be used to improve or treat diseases or conditions mediated by filaggrin deficiency caused by a decrease in filaggrin production or by an increase in filaggrin denaturation.

Claims

1. Use of caprylic acid and capric acid triglycerides as active ingredients in the preparation of a medicament for treating diseases mediated by filaggrin deficiency, wherein the treatment comprises topical application of a therapeutically effective amount of caprylic acid and capric acid triglycerides, wherein the disease mediated by filaggrin deficiency is selected from the group consisting of psoriasis, atopic dermatitis and ichthyosis vulgaris.

2. Use of caprylic acid and capric triglycerides as active ingredients in the preparation of a medicament for treating conditions mediated by collagen deficiency, wherein the treatment comprises topical application of a therapeutically effective amount of caprylic acid and capric triglycerides, wherein the condition mediated by collagen deficiency is skin aging.

3. The use according to claim 1 or 2, wherein the treatment comprises topical application of a combination of caprylic and capric triglycerides and melatonin or a derivative thereof having the formula: wherein each of R1 and R2 is independently selected from the group consisting of H and halogen.

4. Use of a topical composition in the preparation of a medicament for preventing and / or treating a disease mediated by filaggrin deficiency, wherein the treatment comprises topical application of the composition comprising as active ingredients an effective amount of caprylic and capric triglycerides in an amount of 0.1 wt % to 70 wt % of the total weight of the composition, and one or more topically acceptable excipients or carriers, wherein the disease mediated by filaggrin deficiency is selected from the group consisting of psoriasis, atopic dermatitis and ichthyosis vulgaris.

5. Use of a topical composition in the preparation of a medicament for preventing and / or treating a condition mediated by collagen deficiency, wherein the treatment comprises topical application of the composition comprising as active ingredients an effective amount of caprylic and capric triglycerides in an amount of 0.1% to 70% by weight, based on the total weight of the composition, and one or more topically acceptable excipients or carriers, wherein the condition mediated by collagen deficiency is skin aging.

6. The use according to claim 4 or 5, wherein the topical composition is a pharmaceutical topical composition and the treatment comprises topically applying the pharmaceutical topical composition comprising: 0.1% to 70% by weight of a therapeutically effective amount of caprylic and capric triglycerides and 0.004% to 12% by weight of a therapeutically effective amount of melatonin or a derivative thereof as defined in claim 3; and one or more acceptable excipients or carriers.

7. The use according to claim 4 or 5, wherein the topically acceptable excipient or carrier is selected from the group consisting of: water absorbents, emollients, surfactants, thickeners, humectants, pH adjusters, antioxidants, preservatives, vehicles, chelating agents, absorbents and mixtures thereof.

8. The use according to claim 7, wherein the surfactant comprises an emulsifier.

9. Use according to claim 4 or 5, wherein the composition comprises one or more additional active ingredients.

10. The use according to claim 9, wherein the additional active ingredient is selected from the group consisting of cannabinoids, bakuchiol, vitamins or derivatives thereof, peptides, alpha hydroxy acids, alpha amino acids, sunscreen actives and mixtures thereof.

11. The use according to claim 4 or 5, wherein the treatment comprises topical application of the composition comprising an effective amount of caprylic and capric triglycerides in an amount of 55% to 70% by weight, based on the total weight of the composition, and one or more topically acceptable excipients or carriers.

12. The use according to claim 11, wherein the composition comprises: 55 to 70% by weight caprylic and capric triglycerides; 0.004 wt % to 1 wt % of melatonin or a derivative thereof as defined in claim 3; 0.1 wt % to 1 wt % bakuchiol; and 1 to 20% by weight of vitamin C or its derivatives; The sum of the ingredients is 100% by weight.

13. The use according to claim 12, wherein the composition further comprises 20% to 30% by weight of an emollient.

14. The use according to claim 12, wherein the derivative of vitamin C is ascorbyl tetraisopalmitate.

15. The use according to claim 4 or 5, wherein the treatment comprises topical application of the composition comprising an effective amount of caprylic and capric triglycerides in an amount of 1% to 10% by weight, based on the total weight of the composition, and one or more topically acceptable excipients or carriers.

16. The use according to claim 15, wherein the composition comprises: 1 to 10 wt. % caprylic and capric triglycerides; 0.004 wt % to 1 wt % of melatonin or a derivative thereof as defined in claim 3; 0.05 to 1% by weight of carnosine; 0.5 to 6 wt % niacinamide; 0.5 to 5 wt. % betaine; and The sum of the ingredients is 100% by weight.

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