New uses of 4-amidinobenzylamine

Abstract

The present invention relates to the use of certain 4-amidinobenzylamines as ingredients for enhancing skin firmness and elasticity by increasing the expression of type I collagen in the skin.

Description

Detailed Description of the Invention

[0001] The present invention relates to the use of certain 4-amidinobenzylamines as ingredients for enhancing skin firmness and elasticity by increasing the expression of type I collagen in the skin.

[0002] Human skin is the largest organ of the human body and a barrier that separates the body from the external environment. Human skin is composed of several layers classified as the epidermis, dermis and subcutaneous tissue. The epidermis is the outermost layer of the skin and is mainly formed by keratinocytes, which make up about 90% of the epidermis, and melanocytes, which are found at the base of the epidermis and produce melanin. The main function of the epidermis is to form an impermeable barrier against environmental challenges, such as UV radiation, heat, chemicals, pollution, and pathogens, such as bacteria, fungi, parasites and viruses. The epidermis also protects the body from uncontrolled water evaporation from the inside to the outside, maintaining the hydration balance and skin metabolism.

[0003] The dermis is the second layer of the skin. In the dermis, the most abundant cell type is the dermal fibroblast, which is responsible for generating connective tissue by producing the extracellular matrix (ECM). The ECM is a three-dimensional meshwork of extracellular polymers and minerals, such as collagen, enzymes, glycoproteins, and hydroxyapatite. The ECM provides strength and integrity to the skin.

[0004] As the major structural protein of the extracellular matrix (ECM), type I collagen is secreted by fibroblasts and forms more than 90% of the dry weight of the dermis. It is produced as procollagen and then processed into mature collagen.

[0005] During the intrinsic aging of tissues, especially dermis and epidermis, collagen expression decreases, inducing the loosening of these tissues, thus causing skin to lose its integrity and firmness.Various exogenous factors, including irritating environmental factors such as UV radiation, pollution or tobacco, also contribute to the loss of skin firmness.Other intrinsic factors, especially hormonal fluctuations and changes in skin tension (rapid weight gain and loss), can also contribute to collagen fiber disorganization and loss of firmness.

[0006] Thus, there is a continuing need for ingredients that can increase collagen production and therefore combat the loss of skin firmness and / or elasticity.

[0007] Surprisingly, it has now been discovered that certain 4-amidinobenzylamines are capable of significantly increasing the synthesis of type I collagen in human dermal fibroblasts.

[0008] Thus, in a first embodiment, the present invention provides a compound of formula (I) for increasing the firmness and / or elasticity of the skin by increasing the production (i.e. expression) of collagen I, in particular in the skin, and more particularly in human dermal fibroblasts present in the skin. [ka] [Wherein, R is C6 to C 10 is a linear or branched C1-C6 aliphatic hydrocarbon chain, optionally substituted with an aromatic group. The present invention relates to non-therapeutic uses of the compounds.

[0009] In a further aspect, the present invention relates to a method of increasing skin firmness and / or elasticity in a subject, said method comprising the step of administering a compound of formula (I) as outlined above to said subject, in particular to skin areas in need thereof, such as, for example, facial skin, hand skin and skin exposed to light.

[0010] Collagen is responsible for the strength and structure of the skin: collagen homeostasis in the deeper layers of the skin is maintained by balancing degradative and synthetic pathways; an imbalance between collagen production and degradation can result in loss of skin firmness and elasticity.

[0011] It has now been discovered that the compounds of formula (I) as outlined above are capable of increasing type I collagen in human dermal fibroblasts and thus maintaining skin homeostasis.

[0012] The present invention therefore also relates to the use of the compounds of formula (I) as outlined above for increasing the production of type I collagen in fibroblasts and, accordingly, in the skin (compared to untreated controls).

[0013] The present invention also relates to the use of the compounds of formula (I) as outlined above for increasing the expression of collagen type I in fibroblasts (compared to untreated controls).

[0014] Preferably, in all embodiments of the invention, the fibroblasts are human fibroblasts, most preferably human dermal fibroblasts.

[0015] In another aspect, the present invention relates to the use of a compound of formula (I) as outlined above for use in the prevention and / or treatment of a pathological condition involving loss of collagen-1 protein and / or gene expression, pathological loss of skin firmness and / or pathological loss of skin elasticity, comprising the step of administering an effective amount of a compound of formula (I) or a composition comprising a compound of formula (I) to a human subject in need thereof.

[0016] In a further embodiment, the present invention relates to a method for the prevention and / or treatment of a pathological condition involving loss of collagen-1 protein and / or gene expression, pathological loss of skin firmness or skin elasticity and / or pathological loss of elasticity, comprising the step of administering an effective amount of a compound of formula (I) or a composition comprising a compound of formula (I) to a human subject in need thereof.

[0017] In particular, the pathological condition is selected from the group consisting of rosacea, telangiectasia, actinic elastosis, cutis laxa and / or striae.

[0018] In all embodiments of the present invention, the compounds of formula (I) are those in which R is a C6-C 10 R is a linear or branched C1-C6 aliphatic hydrocarbon chain optionally substituted with an aromatic group, preferably R is a linear C1-C3 aliphatic hydrocarbon chain substituted with a C6-C8 aromatic group, more preferably R is a linear C1-C3 aliphatic hydrocarbon chain preferably substituted with a terminal phenyl group (especially phenylmethyl-, phenylethyl- and phenylpropyl- etc.), most preferably R is -CH2-CH2-C6H5 which means that the compound of formula (I) is benzylsulfonyl-Ser-hPhe-4-amidinobenzylamide (formula (II)). [ka]

[0019] In all embodiments of the present invention, the compounds of formula (I) and formula (II) may each be in any stereochemical configuration.

[0020] However, in all embodiments of the present invention, the compounds of formula (I) and (II) may be of formula (Ia) or (IIa) [ka] It is preferable that the compound is

[0021] Preferably, in all embodiments of the present invention, the compounds of formulae (I) and (Ia) and (II) and (IIa) are used in the form of their salts, preferably as salts with inorganic acids, preferably as hydrochlorides, or as salts with suitable organic acids, or as sulfates, for example as acetates or sulfates. Preferred organic acid salts of the compounds of formulae (I), (Ia), (II) and (IIa) are selected from acetates, formates, methylsulfonates, succinates, malates, trifluoroacetates, most preferred are the respective acetates.

[0022] Most preferred in all embodiments of the invention is the use of amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate (CAS number: 1393815-16-1), which is commercially available in the form of SYN®-UP from DSM Nutritional Products Ltd, Kaiseraugst. SYN®-UP is a mixture of amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate (0.1-1 wt.%), water (25-50 wt.%), citric acid (0.1-1 wt.%), sodium hydroxide (less than 0.1 wt.%, for pH adjustment to 2.6-3.6) and glycerin (balance up to 100%). Most preferred in all embodiments of the invention is the use of said mixture (hereinafter also referred to as SYN®-UP mixture).

[0023] For the purposes of the present invention, the terms "increasing the expression of collagen type I" or "increasing the production of collagen I" are intended to mean, respectively, an increase in the expression of collagen I in the presence of a compound of formula (I) as defined herein, preferably measured in human dermal fibroblasts as outlined in the Examples, compared to the expression of collagen detected in the absence of a compound of formula (I), of at least 4%, preferably at least 20%, even more preferably at least 40%, for example in the range of 40-100%.

[0024] The term "subject," as used herein, means an animal having skin that separates and defines the inside of the animal from the outside. Preferably, the subject is a human.

[0025] In one embodiment of the invention, the subject may be female. In another embodiment, the subject may be male. In a further embodiment, the subject may be of non-binary gender.

[0026] In a preferred embodiment, the subject is not a child. The term "child" as used herein means a human being 7 years old or less. Thus, in all embodiments of the present invention, the subject is a human being 8 years old or more, preferably, the subject is a human being 20 years old or more, preferably 30 years old or more, even more preferably 40 years old or more, for example, most preferably 50 years old or more.

[0027] In a further embodiment, increased skin firmness and / or elasticity in a subject is achieved by increasing or maintaining type I collagen production (i.e., expression) or slowing the decline in type I collagen expression in the skin, and / or by maintaining collagen metabolism or slowing the decline in collagen metabolism (expression) in the skin.

[0028] In a further embodiment, the present invention relates to the prevention, reduction or treatment of loss of skin firmness and / or elasticity caused by intrinsic and / or extrinsic factors such as, but not limited to, sunlight, sunburn, collagen damage, aging, infrared radiation, heat, hormonal reasons, nutritional deficiencies, temperature, smoking, stress, sleep deprivation, pollution, or alcohol intake.

[0029] In all embodiments of the present invention, preferably the use is non-therapeutic, ie a cosmetic use intended to beautify the skin.

[0030] In all embodiments of the present invention, the compounds of formulae (I), (Ia), (II) and (IIa), such as in particular amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate or SYN®-UP mixture, are preferably administered in the form of a cosmetic or dermatological composition.

[0031] The term "cosmetic composition", as used herein, refers to a cosmetic composition used to treat, care for or improve the appearance of the skin and / or scalp, preferably the skin, most preferably the facial skin and / or the skin of the hands.

[0032] The term "topical dermatological composition," as used herein, refers to a composition used for application to the skin.

[0033] The total amount of the compounds of formula (I), (Ia), (II) and (IIa), for example and in particular acetic acid amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide, in the composition according to the present invention is preferably selected in the range of 0.00001-0.1 wt.-%, more preferably in the range of 0.0001-0.06 wt.-%, and most preferably in the range of 0.0005-0.03 wt.-%, based on the total weight of the composition. A further suitable range is selected in the range of 0.00001-0.01 wt.-%, more preferably in the range of 0.0001-0.005 wt.-%, and most preferably in the range of 0.0005-0.002 wt.-%.

[0034] The total amount of SYN®-UP mixture in the composition according to the invention is preferably chosen in the range of 0.01 to 10 wt.-%, more preferably in the range of 0.1 to 6 wt.-%, most preferably in the range of 0.5 to 3 wt.-%, based on the total weight of the composition.

[0035] Unless otherwise specified herein, all parts and percentages given are by weight and are based on the total weight of the composition.

[0036] In a particular embodiment, the compounds of formula (I), (Ia), (II) and (IIa), for example and in particular amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate, are used in the compositions according to the invention either in the form of a SYN®-UP mixture or in a mixture with glycerin, water and / or citric acid.

[0037] In a particular embodiment, the composition according to the present invention is a cosmetic composition intended to be applied topically to mammalian keratinous tissue, for example, in particular to human skin or human scalp. Such compositions are also called topical skin compositions. Thus, preferably, in all embodiments of the present invention, the cosmetic composition is a topical cosmetic (i.e. topical skin) composition, with all the definitions and preferences described herein.

[0038] Topical cosmetic compositions according to the present invention may be leave-on or rinse-off compositions and may include any product that is applied to the human body primarily to improve appearance or overall beauty. Preferably, the cosmetic compositions of the present invention are leave-on compositions.

[0039] It will be appreciated that a cosmetic composition according to the invention intended for topical application comprises a physiologically acceptable medium, i.e. a medium compatible with keratinous materials such as the skin, mucous membranes and keratinous fibres. In particular, a physiologically acceptable medium is a cosmetically acceptable carrier. In all embodiments of the invention, the carrier preferably comprises water.

[0040] The term "cosmetically acceptable carrier" (also referred to herein as carrier) refers to all vehicles / carriers conventionally used in cosmetic compositions, i.e., suitable for topical application to keratinous tissue, having good aesthetic properties, compatible with the active ingredients present in the composition, and not raising any unreasonable safety or toxicity concerns. Such carriers are well known to those skilled in the art and may include one or more compatible liquid or solid filler diluents, excipients, additives or vehicles suitable for application to the skin.

[0041] The exact amount of carrier will depend on the actual level of the active ingredient and other optional ingredients that one of ordinary skill in the art would classify as distinct from carriers (eg, other active ingredients).

[0042] In an advantageous embodiment, the cosmetic composition according to the present invention comprises from about 50% to about 99%, preferably from about 60% to about 98%, more preferably from about 70% to about 98%, for example, in particular from about 80% to about 95%, of a carrier, based on the total weight of the cosmetic composition.

[0043] In a particularly advantageous embodiment, the carrier in the cosmetic composition according to the invention consists of at least 30 wt.-%, more preferably at least 40 wt.-% and most preferably at least 45 wt.-% water, for example in particular 50 to 90 wt.-% water.

[0044] In a particularly advantageous embodiment, the cosmetic composition according to the invention comprises glycerin in an amount of 0.005 to 10 wt.-%, preferably in the range of 0.05 to 5 wt.-%, most preferably in the range of 0.25 to 4 wt.-%, for example in the range of 0.25 to 3 wt.-%, based on the total weight of the composition.

[0045] The cosmetic composition according to the invention may be in the form of a solution, a lotion, a thickened lotion, a gel, a cream, an emulsion, an ointment, a paste, a powder, a make-up or a solid tube stick, and may optionally be packaged as an aerosol and may be provided in the form of a mousse, a spray, a stick, e.g. an aerosol mousse, a foam or a spray foam.

[0046] Preferably, the compounds of formula (I), (Ia), (II) and (IIa), for example, especially amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate, preferably in the form of SYN®-UP mixture according to the present invention, are formulated into lotions, creams, gels and tonics. These product forms can be used for multiple applications, including, but not limited to, hand and body lotions, (facial) preparations, makeup products such as foundations, sunscreens and sunless tanning agents, etc. Any additional ingredients required to formulate such products vary depending on the type of product and can be routinely selected by those skilled in the art.

[0047] When the cosmetic composition of the present invention is formulated as an aerosol and applied to the skin as a spray-on product, a propellant is added to the composition.

[0048] The cosmetic compositions according to the present invention can be prepared by conventional methods in the art, for example by mixing a compound of formula (I), (Ia), (II) and (IIa), for example in particular amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate, or a SYN®-UP mixture having all the definitions and priorities described herein, with a cosmetically acceptable carrier.

[0049] The cosmetic composition may contain further ingredients, which may form part of the carrier. Such ingredients are in particular surfactants, emulsifiers, thickeners and oils. Such suitable surfactants, emulsifiers, thickeners and oils are well known to those skilled in the art.

[0050] The cosmetic composition of the present invention (including the carrier) may comprise further conventional (cosmetic) adjuvants and additives such as preservatives / antioxidants, fatty substances / oils, water, organic solvents, silicones, thickeners, emollients, emulsifiers, antifoaming agents, aesthetic ingredients such as fragrances, surfactants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorants / colorants, abrasives, absorbents, chelating and / or sequestering agents, essential oils, skin sensates, astringents, pigments or any other ingredients normally incorporated in such compositions.

[0051] According to the present invention, the composition according to the present invention may also contain further cosmetic active ingredients conventionally used in cosmetic compositions.Exemplary active ingredients include skin whitening agents, UV filters, agents for treating hyperpigmentation, agents for preventing or reducing inflammation, firming agents, moisturizing agents, soothing agents, and / or revitalizing agents, and agents for improving elasticity and skin barrier.

[0052] Unless otherwise specified, the excipients, additives, diluents, etc. described below are suitable for the compositions according to the present invention. The required amounts of cosmetic and dermatological auxiliaries and additives can be easily determined by those skilled in the art based on the desired product.

[0053] Additional ingredients can be added either to the oil phase, the aqueous phase, or added separately, as deemed appropriate. The mode of addition can be readily adapted by one skilled in the art.

[0054] Examples of cosmetic excipients, diluents, adjuvants, additives and active ingredients commonly used in the skin care industry that are suitable for use in the cosmetic compositions of the present invention are described, for example and without limitation, in the International Cosmetic Ingredient Dictionary & Handbook by the Personal Care Product Council (http: / / www.personalcarecouncil.org / ), accessible via the online INFO BASE (http: / / online.personalcarecouncil.org / jsp / Home.jsp).

[0055] The cosmetically active ingredients useful herein can optionally provide more than one benefit or function by more than one mechanism of action.

[0056] Of course, the skilled artisan will carefully select the above-mentioned optional additional components, adjuvants, diluents and additives and / or their amounts such that the advantageous properties inherently associated with the combination according to the present invention are not adversely affected or are not substantially affected by the envisaged addition of one or more.

[0057] The cosmetic composition according to the invention is in particular a skin care formulation or a functional formulation.

[0058] Examples of skin care formulations are in particular sun protection formulations (sun care formulations), lifting formulations, body oils, body lotions, body gels, treatment creams, skin protective ointments, moisturizing formulations such as moisturizing gels or moisturizing sprays, moisturizers for the face and / or body and skin whitening formulations.

[0059] Examples of functional formulations are, but are not limited to, cosmetic compositions containing active ingredients such as hormone formulations, vitamin formulations, plant extract formulations, lifting formulations, and / or antimicrobial (antibacterial or antifungal) formulations.

[0060] The cosmetic composition according to the invention can take a wide variety of forms, including, but not limited to, simple solutions (e.g., aqueous, organic or oil-based), emulsions or microemulsions (especially of the oil-in-water (O / W) or water-in-oil (W / O) type, silicone-in-water (Si / W) or water-in-silicone (W / Si) type, PIT-emulsions, multiple emulsions (e.g., of the oil-in-water-in-oil (O / W / O) or water-in-oil-in-water (W / O / W) type) or Pickering emulsions), and solid forms (e.g., hydrogels, alcohol gels, lipogels, sticks, flowable solids or amorphous materials).

[0061] These product forms can be used in multiple applications including, but not limited to, gels, creams, ointments, lotions, serums, powders, aerosol sprays or two component dispensing systems.

[0062] In a preferred embodiment, the cosmetic composition according to the invention is an emulsion and / or a gel. Even more preferably, the cosmetic composition is an emulsion containing an oily phase and an aqueous phase, such as a multiple emulsion, in particular O / W, W / O, Si / W, W / Si, O / W / O, W / O / W, or a Pickering emulsion.

[0063] The amount of oily phase (i.e. the phase containing all fats and oils including polar oils) present in such emulsions, such as in particular O / W, W / O, Si / W, W / Si, O / W / O, W / O / W multiple emulsions or Pickering emulsions, is preferably at least 10 wt.-%, for example in the range 10 to 60 wt.-%, preferably in the range 15 to 50 wt.-% and most preferably in the range 15 to 40 wt.-%, based on the total weight of the composition.

[0064] The oil phase according to the invention is preferably composed of butylene glycol dicaprylat / -dicaprate, propylene glycol dicaprylat / -dicaprate, dicaprylyl ether, C 12~15 -Alkylbenzoat, C 18~38 - oils selected from fatty acid triglycerides, dibutyl adipate, cyclomethicone, dimethicone, 2-phenylethylbenzoat, isopropyl lauroyl sarkosinate, caprylic / capric triglyceride and mixtures thereof.

[0065] The amount of aqueous phase present in such emulsions is preferably at least 20 wt.-%, for example in the range 20 to 90 wt.-%, preferably in the range 30 to 80 wt.-%, most preferably in the range 30 to 70 wt.-%, based on the total weight of the composition.

[0066] Advantageously, in all emulsions according to the invention, the ratio of oily phase to aqueous phase is chosen in the range from 40:60 to 30:70.

[0067] In one particularly advantageous embodiment, the cosmetic composition according to the invention is in the form of an oil-in-water (O / W) emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O / W emulsifier. The preparation of such O / W emulsions is well known to those skilled in the art.

[0068] When the cosmetic composition according to the invention is an O / W emulsion, it advantageously contains at least one O / W- or Si / W-emulsifier selected from the list: glyceryl stearate citrate, glyceryl stearate SE (self-emulsifying), stearic acid, salts of stearic acid, polyglyceryl-3-methylglycose distearate. Further suitable emulsifiers are phosphoric acid esters and their salts, such as cetyl phosphate (for example as Amphisol® A from DSM Nutritional Products Ltd.), diethanolamine cetyl phosphate (for example as Amphisol® DEA from DSM Nutritional Products Ltd.), potassium cetyl phosphate (for example as Amphisol® K from DSM Nutritional Products Ltd.), sodium cetearyl sulfate, sodium glyceryl oleate phosphate, hydrogenated vegetable glyceride phosphates and mixtures thereof. Further suitable emulsifiers are sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, cetearyl glucoside, lauryl glucoside, decyl glucoside, sodium stearoyl glutamate, sucrose polystearate and hydrated polyisobutene.Furthermore, one or more synthetic polymers may be used as emulsifiers, such as PVP eicosene copolymer, (acrylates / alkyl acrylate (C10-30)) crosspolymer and mixtures thereof.

[0069] The at least one O / W emulsifier or Si / W emulsifier, respectively, is preferably used in an amount of 0.5 to 10 wt.-%, in particular in the range of 0.5 to 6 wt.-%, such as more particularly in the range of 0.5 to 5 wt.-%, such as most particularly in the range of 1 to 4 wt.-%, based on the total weight of the cosmetic composition.

[0070] Particular suitable O / W emulsifiers to be used in the cosmetic composition according to the invention include phosphate ester emulsifiers, such as, advantageously, 8-10 alkyl ethyl phosphate, C9-15 alkyl phosphate, ceteareth-2 phosphate, ceteareth-5 phosphate, ceteth-8 phosphate, ceteth-10 phosphate, cetyl phosphate, C6-10 pareth-4 phosphate, C12-15 pareth-2 phosphate, C12-15 pareth-3 phosphate, DEA-ceteareth-2 phosphate, DEA-cetyl phosphate, DEA-oleth-3 phosphate, potassium cetyl phosphate, deceth-4 phosphate, deceth-6 phosphate and trilaureth-4 phosphate.

[0071] A particularly suitable O / W emulsifier to be used in the cosmetic composition according to the invention is, for example, potassium cetyl phosphate, commercially available as Amphisol® K from DSM Nutritional Products Ltd, Kaiseraugst.

[0072] Another particularly suitable class of O / W emulsifiers are the non-ionic self-emulsifying systems derived from olive oil, known for example as (INCI name) cetearyl olivate and sorbitan olivate (chemical composition: sorbitan and cetearyl esters of olive oil fatty acids) and sold under the trade name OLIVEM 1000.

[0073] In one particular embodiment, the present invention relates to a cosmetic composition with all the definitions and preferences described herein, in the form of an O / W emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O / W emulsifier, the O / W emulsifier being potassium cetyl phosphate. The amount of oily phase in such an O / W emulsion is preferably at least 10 wt.-%, more preferably in the range of 10 to 60 wt.-%, most preferably in the range of 15 to 50 wt.-%, for example in the range of 15 to 40 wt.-%, based on the total weight of the composition.

[0074] Preferably, the cosmetic composition according to the invention further comprises at least one fatty alcohol (co-emulsifier), such as in particular cetyl alcohol, cetearyl alcohol and / or behenyl alcohol. The total amount of the fatty alcohol or alcohols in the topical composition according to the invention is preferably chosen in the range of about 0.1 to 10.0 wt.-%, in particular in the range of about 0.5 to 6.0 wt.-%, based on the total weight of the topical composition.

[0075] Preferably, the topical composition according to the invention comprises a thickener to help achieve the appropriate consistency of the product, especially when the topical composition is in the form of an emulsion. Preferred thickeners are aluminum silicate, xanthan gum, hydroxypropylmethylcellulose, hydroxyethylcellulose, polyacrylates such as Carbopol® (e.g. Carbopol 980, 981, 1382, 2984, 5984), or mixtures thereof. Further preferred thickeners are acrylate / C 10~30 These include alkyl acrylate copolymers (eg, Pemulen TR1, Pemulen TR2, Carbopol 1328, etc. by NOVEON) and Aristoflex AVC (INCI: (Ammonium Acryloyldimethyltaurate / VP) Copolymer).

[0076] The cosmetic composition according to the invention advantageously comprises a preservative, which, if present, is preferably used in an amount of 0.1 to 2 wt.-%, more preferably 0.5 to 1.5 wt.-%, based on the total weight of the composition.

[0077] Cosmetic compositions according to the present invention generally have a pH in the range of 3 to 10, preferably a pH in the range of 4 to 8, most preferably a pH in the range of 4 to 7.5, for example a pH in the range of 5 to 6.5. The pH can be readily adjusted as desired using a suitable acid, such as citric acid, or a base, such as sodium hydroxide (e.g. as an aqueous solution), triethanolamine (TEA Care), tromethamine (Trizma Base) and aminomethylpropanol (AMP-Ultra PC2000), according to standard methods in the art.

[0078] The amount of cosmetic composition to be applied to the skin is not critical and can be easily adjusted by one skilled in the art. Preferably, the amount is between 0.1 and 3 mg / cm. 2 In the area of ​​the skin, for example, preferably 0.1 to 2 mg / cm 2 In the skin area, most preferably 0.5-2 mg / cm 2 Selected according to skin area.

[0079] The following examples are provided to further illustrate the compositions and effects of the present invention. These examples are merely illustrative and are not intended to limit the scope of the present invention in any way.

[0080] [Example] [Brief Description] Amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate (ABSHA) was evaluated for its effect on collagen type 1. This was done using an in vitro dermal fibroblast collagen assay. Amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate was found to increase collagen expression.

[0081] [method] Human normal dermal fibroblasts were seeded in cell culture medium (Dulbecco's modified Eagle's medium supplemented with 10% serum and 1% antibiotics) and allowed to adhere in a humidified cell incubator while maintained at 37°C and 5% CO2. Later, the cells were starved for 16-24 hours in serum-free culture medium to synchronize the cells to their cell cycle. The starvation medium was removed and cell culture medium + SYN®-UP (at various concentrations) was added to the cells. The cells were treated for 72 hours. The cells were then fixed and immunolabeled with an antibody specific for collagen 1. These labeled cells were analyzed using flow cytometry and compared to untreated cells (medium without SYN®-UP).

[0082] [result]

[0083] [Table 1]

[0084] Table 1. Treatment of human normal dermal fibroblasts with several concentrations of amidinobenzyl benzylsulfonyl D-seryl homophenylalaninamide acetate (ABSHA) for 72 hours resulted in an increase in collagen type 1 protein. Data are normalized to the untreated control (100%) and are presented as mean ± SD (n=4).

Claims

1. 2. A composition comprising a compound of formula (I) for increasing the production of type I collagen and thereby enhancing skin firmness and / or elasticity. 【Chemistry 1】 [In the formula, R is C ６ ~C １０ Linear or branched C optionally substituted with aromatic groups １ ~C ６ aliphatic hydrocarbon chains] Non-therapeutic uses of the compounds.

2. R is C ６ ~C ８ Aromatically substituted linear C １ ~C ３ is an aliphatic hydrocarbon chain, preferably R is a linear C １ ~C ３ 2. The non-therapeutic use according to claim 1, wherein R is an aliphatic hydrocarbon chain, most preferably R is a phenylmethyl-, phenylethyl- or phenylpropyl- group.

3. R is -CH ２ -CH ２ -C ６ H ５ 3. The non-therapeutic use according to claim 1 or 2,

4. The non-therapeutic use according to any one of claims 1 to 3, wherein the compound of formula (I) is amidinobenzyl benzylsulfonyl D-serylhomophenylalaninamide acetate.

5. The non-therapeutic use according to any one of claims 1 to 4, wherein the compound of formula (I) increases the production of type I collagen in human dermal fibroblasts.

6. The non-therapeutic use according to any one of claims 1 to 5, wherein the use is in the form of a cosmetic composition or a skin topical composition comprising the compound of formula (I).

7. 7. The non-therapeutic use according to claim 6, wherein the amount of said compound of formula (I) in said composition is selected in the range of 0.00001 to 0.1 wt.-%, more preferably in the range of 0.0001 to 0.06 wt.-%, most preferably in the range of 0.0005 to 0.03 wt.-%, based on the total weight of the composition.

8. 8. The non-therapeutic use according to claim 6 or 7, wherein the composition is a leave-on composition.

9. Non-therapeutic use according to any one of claims 6 to 8, wherein the composition comprises a carrier consisting of at least 30 wt.-%, more preferably at least 40 wt.-%, most preferably at least 45 wt.-% water, for example, in particular 50 to 90 wt.-% water.

10. The non-therapeutic use according to any one of claims 6 to 9, wherein the composition is an O / W emulsion comprising an oily phase dispersed in an aqueous phase.

11. A non-therapeutic method of enhancing skin firmness and / or elasticity in a subject, preferably in a subject aged 30 years or older, preferably aged 40 years or older, most preferably aged 50 years or older, said method comprising administering to an area of ​​the skin in need thereof a compound of formula (I). 【Chemistry 2】 [In the formula, R is C ６ ~C １０ Linear or branched C optionally substituted with aromatic groups １ ~C ６ aliphatic hydrocarbon chains] A non-therapeutic method comprising the step of administering a cosmetic composition comprising a compound of formula (I).

12. R is C ６ ~C ８ Aromatically substituted linear C １ ~C ３ is an aliphatic hydrocarbon chain, preferably R is a linear C １ ~C ３ A non-therapeutic method according to claim 11, wherein R is an aliphatic hydrocarbon chain, most preferably R is a phenylmethyl-, phenylethyl- or phenylpropyl- group.

13. A non-therapeutic method according to claim 11 or 12, wherein the amount of said compound of formula (I) in said composition is selected in the range of 0.00001 to 0.1 wt.-%, more preferably in the range of 0.0001 to 0.06 wt.-%, most preferably in the range of 0.0005 to 0.03 wt.-%, based on the total weight of said composition.

14. The amount of the composition to be applied to the skin is 0.1 to 3 mg / cm ２ In the area of ​​the skin, for example, preferably 0.1 to 2 mg / cm ２ In the area of ​​skin, most preferably 0.5-2 mg / cm ２ A non-therapeutic method according to any one of claims 11 to 13, selected in the area of ​​the skin.

15. 2. The use of a compound of formula (I) for increasing the expression of type I collagen in human fibroblasts 【Chemistry 3】 [In the formula, R is C ６ ~C １０ Linear or branched C optionally substituted with aromatic groups １ ~C ６ aliphatic hydrocarbon chains] Non-therapeutic uses of the compounds.

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