Compositions for treating hair, scalp, and skin

Abstract

The present invention relates to a composition containing, in addition to caffeine, dimethylglycine and / or a salt of dimethylglycine. Furthermore, the present invention relates to the use (cosmetic and / or pharmaceutical) of this composition for the treatment of hair, scalp and / or skin.

Description

[Technical Field]

[0001] The present invention relates to a composition containing caffeine, in addition to dimethylglycine and / or a salt of dimethylglycine. Furthermore, the present invention relates to the use of this composition (as a cosmetic and / or pharmaceutical) for the treatment of hair, scalp and / or skin. [Background technology]

[0002] Human hair has largely lost its importance as a protective function for the body. However, healthy hair holds great cultural significance for women and men worldwide and is often considered a symbol of wealth and health. As a result, thinning hair, for example, caused by hair loss, often negatively impacts quality of life. Hair loss caused by hormones such as androgens is known as androgenetic alopecia (male pattern baldness or AGA) and is the most common cause of hair loss, especially in women as well as men. Distinctions can be made between patterns of hair loss in men and women.

[0003] Hair growth and regrowth depend on a proper supply of nutrients to the hair follicles, provided by the blood. Therefore, reduced blood flow (microcirculation) in the scalp can promote or even cause hair loss. For example, bald individuals have significantly less blood flow to the crown of their scalp than people with normal hair growth. This significantly reduced microcirculation can therefore explain hair loss and the lack of hair regrowth (transition from resting to growth phase), for example, in androgenetic alopecia. Generally speaking, hair loss is considered one of the main clinical signs of reduced blood flow in peripheral blood vessels.

[0004] Caffeine is found in the seeds, nuts, and leaves of a variety of plants native to Africa, East Asia, and South America, with the most well-known source being the so-called coffee bean, i.e., the seed of the coffee plant. Caffeine is known for various pharmacological effects. Caffeine is known for its stimulating effect on the central nervous system. Caffeine is considered the most commonly used psychoactive substance in the world, and unlike other psychoactive substances, it is legal and virtually unregulated worldwide. For example, caffeine can be taken orally through beverages such as coffee and tea, and a succession of pieces of evidence suggest that oral caffeine intake may have positive effects on certain functional disorders.

[0005] Furthermore, its relatively easy penetration through the skin barrier makes caffeine a suitable compound for topical application. Therefore, European application EP1 396 261 A1 describes the use of caffeine as an active ingredient in skin care compositions, and the use of caffeine-containing skin care compositions in particular the care of men's skin, and methods for producing such skin care compositions. The use of caffeine assists in epidermal regeneration, particularly in men's skin. The use of caffeine in the treatment of androgenetic alopecia is discussed, among other things, in Daniels, G., Akram, S., Westgate, GE and Tamburic, S. (2019), Can plant-derived phytochemicals provide symptom relief for hair loss? A critical review. Int J Cosmet Sci, 41:332~345. doi:10.1111 / ics.12554.

[0006] To date, there have been very few approved drug treatments for hair loss, such as androgenic alopecia, and existing treatments are either not sufficiently effective or have unpleasant side effects. The situation is similarly unsatisfactory regarding treatment options for acute onset of circular hair loss caused by inflammation, also known as alopecia areata or AA, and for hair loss caused by other factors.

[0007] In addition to hair, which is essentially a skin appendage, the functionality of the skin is also crucial for a healthy appearance. Physiological effects that affect hair or hair follicles (such as inflammation) similarly affect the skin. Therefore, skin treatment is extremely important for both medical reasons, such as improved protective function and enhanced barrier properties, and purely cosmetic and aesthetic reasons, such as smoother, simpler, and more beautiful skin.

[0008] Therefore, there is still a need for improved topical treatments to combat hair loss, particularly for compositions that have no or negligible side effects. Specifically, there is a need for compositions that are originally intended for pharmaceutical use and therefore have no side effects, or compositions originally intended for cosmetic use.

[0009] There is also a need for improved skin care compositions that improve both the feel and appearance of the skin, while simultaneously strengthening the skin's protective and barrier functions. [Disclosure of the Invention]

[0010] Based on this, the object of the present invention was to provide a well-tolerated composition for the treatment of hair, scalp, and skin, particularly for the prevention and / or treatment of hair loss. Furthermore, this composition should be able to be applied topically and should overcome the shortcomings of compositions known from the prior art.

[0011] Surprisingly, this objective was achieved by the composition described in claim 1 and its use as described in claim 7. Preferred embodiments are specified in the dependent claims.

[0012] According to the present invention, this objective is achieved by providing a composition comprising (A) dimethylglycine and / or a salt of dimethylglycine and (B) caffeine.

[0013] Surprisingly, the combination of active ingredients according to the invention (caffeine and dimethylglycine and / or salts of dimethylglycine) has been shown to have improved effectiveness in the treatment of hair loss, particularly hereditary and age-related hair loss, compared to that of caffein or dimethylglycine and / or salts of dimethylglycine alone. The combination of active ingredients increases the microcirculation in the skin and scalp to an unexpected extent and significantly improves the supply of nutrients and oxygen to the skin and hair roots. Furthermore, this is very well tolerated by the skin both for medical and cosmetic use.

[0014] Dimethylglycine (N,N-dimethylglycine) is found in plants, animals and humans, but is formed only in very small amounts in humans. Dimethylglycine is formed as an intermediate in the multi-step biosynthesis of glycine from choline by aminotransfer of the amino group of betaine by betaine homocysteine methylase.

[0015] N,N-dimethylglycine is also called (dimethylamino)acetic acid and is represented by the following Chemical Formula 1.

[0016]

Chem.

[0017] The invention is not only the use of dimethylglycine, but also the use of its salts, solvates and hydrates. These are preferably pharmaceutically or cosmetically acceptable salts of dimethylglycine. The salts are particularly preferably water-soluble salts having a solubility in water of at least 10 g / l at 20 °C.

[0018] In a preferred embodiment, the salt of dimethylglycine is an alkali, alkaline earth or ammonium salt of dimethylglycine.

[0019] Examples include sodium, potassium, calcium, magnesium, and ammonium salts. In ammonium salts, each ammonium cation independently holds 1 to 4 alkyl groups, each having 1 to 4 carbon atoms. Preferred are the sodium and potassium salts of dimethylglycine, particularly the sodium salt of dimethylglycine, i.e., N,N-dimethylglycine sodium.

[0020] In alternatively preferred embodiments, the salt of dimethylglycine may be a salt of an inorganic and / or organic acid with dimethylglycine.

[0021] Examples of dimethylglycine salts with inorganic acids include dimethylglycine hydrochloride, hydrobromide, hydroiodide, bisulfate, sulfate, bisulfite, sulfite, bicarbonate, carbonate, monophosphate, diphosphate, and triphosphate, and mixtures thereof. Particularly preferred is dimethylglycine hydrochloride.

[0022] Examples of dimethylglycine salts with organic acids include dimethylglycine acetate, lactate, citrate, succinate, fumarate, maleate, and benzoate, and mixtures thereof.

[0023] It is assumed that dimethylglycine and / or salts of dimethylglycine according to the present invention improve oxygen turnover and cellular activity in keratinocytes, and therefore also promote cellular activity in skin and hair follicles. Furthermore, the skin barrier is strengthened, wound healing is supported, and the skin becomes smoother. According to the present invention, dimethylglycine and / or salts of dimethylglycine according to the present invention achieve remarkable hair root and skin strengthening effects, particularly in the treatment of daily or age-related, stressed or weakened skin and hair loss, such as hereditary and age-related hair loss, and remarkably clearly support the effects of caffeine according to the present invention.

[0024] The IUPAC name for caffeine is 1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione. Alternatively, caffeine is also called 1,3,7-trimethylxanthine. Caffeine is represented by the following chemical formula 2.

[0025] [ka]

[0026] Caffeine is a methylxanthine alkaloid belonging to the methylxanthine class. Caffeine is a bitter crystalline substance, sometimes considered a purine derivative, and is chemically related to the adenine and guanine bases of deoxyribonucleic acid and ribonucleic acid.

[0027] The composition according to the present invention contains dimethylglycine and / or a salt of dimethylglycine in a proportion of preferably 0.001% to 10.0% by weight, based on the total weight of the composition. In a preferred embodiment, the composition according to the present invention contains dimethylglycine and / or a salt of dimethylglycine in a proportion of 0.01% to 8.0% by weight, more preferably 0.1% to 6.0% by weight, more preferably 0.3% to 5.0% by weight, and particularly 0.5% to 3.0% by weight, based on the total weight of the composition in each case. In preferred embodiments of the present invention, the compositions according to the present invention may contain 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1.0% by weight, 1.1% by weight, 1.2% by weight, 1.3% by weight, 1.4% by weight, 1.5% by weight, 2.0% by weight, or 2.5% by weight of dimethylglycine and / or salts of dimethylglycine, based on the total weight of the composition in each case. Preferably, the compositions according to the present invention contain dimethylglycine and / or salts of dimethylglycine as pure chemical substances, including each solvate and hydrate (e.g., dihydrate of sodium dimethylglycine), in order to increase the purity of the composition and reduce the incidence of undesirable side effects.

[0028] In a preferred embodiment, the composition according to the present invention contains caffeine in a proportion of 0.001% to 3.0% by weight, more preferably 0.005% to 2.50% by weight, more preferably 0.01% to 2.0% by weight, and particularly 0.1% to 1.5% by weight, based on the total weight of the composition in each case. In a preferred embodiment of the present invention, the composition according to the present invention may contain caffeine in a proportion of 0.01% by weight, 0.05% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1.0% by weight, 1.1% by weight, 1.2% by weight, 1.3% by weight, 1.4% by weight, or 1.5% by weight, based on the total weight of the composition in each case.

[0029] The weight ratio of dimethylglycine and / or a salt of dimethylglycine to caffeine is preferably in the range of 10:1 to 1:10, preferably 6:1 to 1:6, more preferably 4:1 to 1:4, and particularly preferably 2:1 to 1:2. In a preferred embodiment of the present invention, the weight ratio of dimethylglycine and / or a salt of dimethylglycine to caffeine is 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0.

[0030] In a preferred embodiment, the composition according to the present invention may contain at least one other active ingredient, the at least one other active ingredient being selected from menthol, biotin, PCA zinc, niacinamide, panthenol, ectoin, ubiquinone-10, taurine, pantolactone, echinacea, carnitine, tocopherol acetate, and combinations thereof.

[0031] Menthol is a monocyclic monoterpene alcohol and may be added to the composition according to the present invention as an active ingredient that stimulates blood flow. Furthermore, menthol can induce a refreshing sensation on the scalp.

[0032] Biotin, also known as vitamin B7 or vitamin H, is a water-soluble vitamin derived from the B group. According to this invention, biotin can further reduce hair loss and strengthen the skin.

[0033] PCA zinc is a zinc salt of L-pyrrolidone carboxylic acid and may be added to the composition according to the present invention as a substance having antibacterial effects.

[0034] Niacinamide (also known as nicotinamide) is an amide of nicotinic acid and is also known as vitamin B3. In addition to other properties such as reducing oxidative stress, the niacinamide according to the present invention has a hair growth stimulating effect.

[0035] Panthenol is a provitamin that is converted in the body to pantothenic acid (vitamin B5). The latter is part of coenzyme A and is therefore important for skin metabolism. According to the present invention, skin elasticity and moisture are further improved by the action of panthenol. Furthermore, itching and inflammation are alleviated and wound healing is promoted.

[0036] Ectoin is a cyclic amino acid that exists in aqueous solutions as a resonance-stabilized zwitterion. Ectoin has moisturizing effects and, according to this invention, further stabilizes the natural structure of hair. It has also been shown that ectoin protects against UV irradiation and may be useful in the treatment of inflammatory diseases.

[0037] Ubiquinone-10 (Q10 or coenzyme Q) 10 Q10, belonging to the ubiquinone pool, is considered an antioxidant and, according to the present invention, has a stabilizing effect on hair and especially on hair follicles.

[0038] According to the present invention, taurine, or 2-aminoethanesulfonic acid, as an antioxidant also has a further stabilizing effect on the skin and hair, and especially on the hair follicles.

[0039] Pantolactone is derived from a group of substituted lactones, and according to the present invention, it further stimulates hair follicle growth factors.

[0040] According to the present invention, echinacea has a soothing effect on the skin and scalp, relieving itching and tension. Furthermore, echinacea can stimulate blood circulation in the scalp, thus supplying oxygen and nutrient-rich blood to the hair follicles, resulting in a further stabilizing effect on the hair and especially the hair roots.

[0041] Carnitine likely inhibits the formation of hair growth inhibiting factors, and thus, according to the present invention, it also acts against hair loss.

[0042] Tocopherol acetate exhibits antioxidant properties, and according to the present invention, it has an additional stabilizing effect on the skin, hair, and especially hair follicles.

[0043] In a preferred embodiment of the present invention, the composition according to the present invention contains at least one other active ingredient selected from menthol, biotin, PCA zinc, niacinamide, panthenol, ectoin, ubiquinone, taurine, pantolactone, echinacea, carnitine, tocopherol acetate, and combinations thereof, each in a proportion of 0.001% to 10.0% by weight, more preferably 0.005% to 7.50% by weight, even more preferably 0.01% to 5.0% by weight, and particularly 0.1% to 3.0% by weight, based on the total weight of the composition.

[0044] Furthermore, the composition according to the present invention is preferably water-based. This means that the composition preferably contains 45.0% to 85.0% by weight of water.

[0045] The composition preferably has a viscosity of 800-6000 mPa·s, particularly preferably 1000-5700 mPa·s, and very preferably 2500-5500 mPa·s, when measured in a plate-plate configuration (rotating body PP60 Ti) at 20°C and a shear rate of 10 / s using a rheometer Haake RheoStress1 (ThermoFisher Scientific) according to DIN53019-1:2008-09, especially for application to the skin / skin treatment.

[0046] In one embodiment, the composition comprises a surfactant. The surfactant may be anionic, nonionic, cationic, or zwitterionic. The surfactant is preferably anionic or nonionic, particularly anionic or nonionic surfactant that is as mild as possible (i.e., particularly gentle on the skin). According to the present invention, nonionic surfactants are used particularly for their very good emulsifying properties and excellent skin care properties. Anionic surfactants are preferred because they have particularly high cleansing performance. Therefore, anionic surfactants are particularly useful in cleansing compositions such as shampoos. Cationic surfactants have excellent hair care properties and, according to the present invention, are used particularly in hair care compositions such as conditioners, shampoos, and treatments.

[0047] The compositions according to the present invention contain, in each case, a surfactant in an amount of preferably 2% to 40% by weight, particularly 5% to 30% by weight, preferably 7% to 20% by weight, and especially preferably 10% to 17% by weight, based on the total weight of the composition. Suitable amounts of surfactant are, in each case, based on the total weight of the composition, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 21% by weight, 22% by weight, 23% by weight, 24% by weight, and 25% by weight. The topical compositions of the present invention particularly contain, in each case, an amount of 0.1% to 20% by weight, preferably 1% to 17% by weight, and especially preferably 5% to 15% by weight, based on the total weight of the composition, one or more anionic surfactants. The preferred amounts of anionic surfactant are 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, and 20% by weight, based on the total weight of the composition in each case. At these amounts, the surfactant has particularly high cleaning performance and is very well tolerated by the skin, scalp, and hair.

[0048] The surfactants of the present invention are described, in particular, in the book "Surfactants and Interfacial Phenomena" by Milton Rosen and Joy Kunjappu, published by John Wiley & Sons, Inc., 2012, 4th edition.

[0049] In preferred embodiments, the surfactant is an anionic surfactant selected from alkyl sulfonates, alkyl sulfates, alkyl ether sulfates, alkyl phosphates, alkyl sarcosine salts, alkyl taurate salts, amino acid surfactants, and mixtures thereof. More preferably, the surfactant is selected from alkyl sulfates, alkyl sarcosine salts, alkyl taurate salts, alkyl glutamates such as sodium cocoyl glutamate / disodium cocoyl glutamate, alkyl glycine salts, alkyl alanine salts such as sodium cocoyl alanine, and mixtures thereof. Also preferred for their cleaning performance are fatty alcohol polyglycerol ether sulfates, monoglyceryl sulfates, mono and / or dialkyl sulfosuccinates, fatty acid isethionates, and α-olefin sulfonates.

[0050] Alkyl sulfates have the general formula ROSO3M, alkyl sarcosine salts have the general formula RC(O)N(CH3)CH2CO2M, and alkyl taurine salts have the general formula RC(O)N(CH3)CH2CH2SO3M, where each R is C4~C 26 Alkyl or C4-C 26 It is an alkenyl, where M is a water-soluble cation such as ammonium, sodium, or potassium. Preferably, M is a sodium cation. Preferably, R is C 12 ~C 16 Alkyl or C 12 ~C 18 It is alkyl.

[0051] In one embodiment, the surfactant is a nonionic surfactant. Non-limiting examples of nonionic surfactants include glycerol fatty acid esters, polyoxyethylene ethers of one or more fatty alcohols, alkoxylated fatty acid alkyl esters, polyglycerol ethers of fatty alcohols, polyglycerol esters of fatty acids, polyethylene glycol and / or polypropylene glycol ethers, fatty acid amides, alkylphenol polyglycol ethers, amine oxides, and alkyl polyglucosides.

[0052] In one embodiment, the surfactant is selected from the group consisting of glycerol fatty acid esters, polyoxyethylene ethers of one or more fatty alcohols, polyglycerol ethers of fatty alcohols, polyglycerol esters of fatty acids, and mixtures thereof.

[0053] In the present invention, the term "glycerol fatty acid ester" refers to glycerol mono- or glycerol di-fatty acid esters. Glycerol di-fatty acid esters have the formula R 3 -COO-(CH2CH(OH)CH2)-OOR 4 or R 3 -COO-(CH2CH(OOR 4 )CH2)-OH. Glycerol mono-fatty acid esters have the formula R 3 -COO-(CH2CH(OH)CH2)-OH or HO-(CH2CH(OOR 3 )CH2)-OH. Here, R 3 and R 4 are independently selected from C6-C 28 alkyl and C6-C 28 alkenyl. Glycerol mono-fatty acid esters contain a glycerol group bonded to one fatty acid via an ester bond. Examples are glycerol monostearate, glycerol monobehenate, glycerol monocaprylate, glycerol monocaprate, and glycerol monolaurate.

[0054] The polyoxyethylene ether is a compound of the formula R 5 (OC2H3) n OH, wherein R 5 is C6-C 28 alkyl, C6-C 28The group is selected from alkenyl, substituted, and unsubstituted phenoxy groups, where n is an integer greater than 1. The polyoxyethylene ether of one or more fatty alcohols is preferably selected from the group consisting of steareth-2, steareth-21, macrogol cetostearyl ether-12, ceteareth-25, macrogol cetostearyl ether-20, and mixtures of the above compounds. More preferably, the polyoxyethylene ether is a compound selected from the group consisting of ceteareth-25, macrogol cetostearyl ether-20, and mixtures of the above.

[0055] The term "polyglycerol ether of fatty alcohol" is expressed by formula R 6 O-(C3H6O2) n -H refers to a compound, in which R 6 It is branched or linear C6~C 28 Alkyl or C6-C 28 The component is an alkenyl, where n is an integer greater than 1, preferably an integer between 2 and 10. The composition preferably contains 0.01 to 15.0% by weight, 0.1 to 10.0% by weight, or 1 to 5.0% by weight of polyglycerol ether.

[0056] The term "polyglycerol ester of fatty acid" refers to a polyglycerol moiety and at least one C6-C6 compound. 26 Alkyl or C6-C 26 This refers to compounds containing both the alkenylcarboxylic acid moiety and the alkenylcarboxylic acid moiety. These compounds are given by formula R 7 -R 8 -(C3H6O2) n -H may be present, in the formula, R 7 is C6~C 26 Alkanic acid or C6-C 26 It is an alkenoic acid group, R 8 This is a suitable linking molecule or direct bond. Therefore, the polyglycerol moiety and C6~C 26 Alkyl or C6-C 26The alkenylcarboxylic acid portion may be directly bonded via an ester bond, or it may contain a bonding site that connects these two portions. Non-limiting examples of this group include polyglyceryl 3-methyl glucose distearate, polyglycerol polyclinoleate, polyglyceryl dimerate isostearate, polyglyceryl 2 laurate, polyglyceryl 2 sesquiisostearate, polyglyceryl 3 distearate (Cremophor GS 32), polyglyceryl 3 oleate, polyglyceryl 3-methyl glucose distearate, polyglyceryl 4 caprate (polyglycerol T2010190), polyglyceryl 4 (diisostearate / polyhydroxystearate / sebacate) (Isolan GPS), and polyglyceryl 4 isostearate.

[0057] In one embodiment, the surfactant includes cationic surfactants such as quaternary surfactants. Quaternary surfactants contain at least one N atom covalently bonded to four alkyl or aryl groups. Regardless of the pH value, this leads to a positive charge. Alkyl betaines, alkylamidopropyl betaines, and alkylamidopropyl hydroxysulfine are advantageous. Cationic surfactants used in the present invention may also be selected from the group of quaternary ammonium compounds, particularly benzyltrialkylammonium chloride or bromide such as benzyldimethylstearylammonium chloride, as well as alkyltrialkylammonium salts, e.g., cetyltrimethylammonium chloride or bromide, alkyldimethylhydroxyethylammonium chloride or bromide, dialkyldimethylammonium chloride or bromide, alkylamidoethyltrimethylammonium ether sulfate, alkylpyridinium salts, e.g., lauryl or cetylpyrimidinium chloride, imidazoline derivatives, and cationic compounds such as amine oxides, e.g., alkyldimethylamine oxide or alkylaminoethyldimethylamine oxide. The use of cetyltrimethylammonium salts is particularly advantageous.

[0058] In further embodiments, the compositions according to the present invention contain at least one additive. Preferred additives are those commonly used in shampoos, conditioners, and emulsions for treating skin, scalp, and hair. The at least one additive may be present in an amount of 0.01% to 12.0% by weight, more preferably 0.25% to 10.0% by weight, and particularly 1.0% to 7.0% by weight.

[0059] At least one additive may be selected from the group consisting of hair conditioners, lipid replenishers, preservatives, stabilizers, fragrances, antioxidants, rheology modifiers, thickeners, conditioning agents, pigments, pearlescent agents, whitening agents, solvents, pH adjusters (including buffer systems), and combinations thereof.

[0060] Hair conditioners can reduce static charge in hair by neutralizing the charge on the hair surface. An example of a hair conditioning agent is a quaternary ammonium compound.

[0061] Lipid supplements, also known as lipid replacement agents or superlipids, are lipophilic substances that can prevent disruption of the epidermal barrier function. Examples of lipid supplements include lanolin, squalene, liquid paraffin, vegetable oils, silicones, and cetyl palmitate.

[0062] A preservative is a substance used to preserve a composition by stopping and / or inhibiting the growth of microorganisms that degrade the composition. Preferably, the preservative may be selected from the group consisting of benzoic acid, benzoic acid derivatives, sorbic acid, sorbic acid derivatives, salicylic acid, salicylic acid derivatives, phenoxyethanol, parabens, and combinations thereof. In a preferred embodiment, sodium benzoate and / or potassium sorbate are used as preservatives in the composition according to the present invention. Sodium benzoate releases benzoic acid, and potassium sorbate releases sorbic acid, in a slightly acidic environment. The antimicrobial effect is due to both acids.

[0063] The stabilizer can protect the photosensitive component from irradiation and is preferably a UV absorber such as a benzophenone derivative.

[0064] The addition of fragrances can give a composition a pleasant scent. Examples include fragrances known to those skilled in the art.

[0065] An antioxidant is a compound that inhibits or completely suppresses the oxidation of other components in the composition of the present invention. Possible examples of antioxidants include citric acid, ascorbic acid, and butylhydroxyanisole.

[0066] Rheology modifiers and thickeners can help improve the coating properties of the compositions of the present invention. The addition of table salt (sodium chloride) is considered a rheology modifier and thickener. The fluidity of the compositions according to the present invention may be affected within certain limits and may be adjusted to a desired level by adding sodium chloride. Cellulose derivatives or polyacrylates may also be used as thickeners.

[0067] In the context of topical application, care products should be understood to mean substances that care for the hair and / or (scalp) skin. Hydrolyzed wheat protein and allantoin nourish the scalp and hair. Hydrolyzed wheat protein primarily possesses moisturizing properties.

[0068] Dyes are optionally used to give the compositions of the present invention a characteristic color so that they can be easily distinguished from other products. However, within the scope of the present invention, dyes can also be used to dye human hair.

[0069] Solvents or solvent mixtures that are customary to those skilled in the art can be used as solvents. Preferred solvents are ethanol or butylene glycol, particularly 1,4-butylene glycol, propylene glycol, and isopropyl alcohol. Ethanol is preferred. These solvents may preferably be contained in the composition according to the present invention in an amount of 0.1% to 70% by weight. The solvent may preferably be contained in a composition that remains on the head when used (leave-on formulation). Their use may lead to a refreshing feeling and have very little effect on the hairstyle due to quick drying. Furthermore, the solvent helps the penetration of the active ingredients, and thus increases their effectiveness.

[0070] Suitable pH adjusters may be acids, bases, and / or buffer systems for stabilizing or influencing the pH of the composition. Typical pH adjusters according to the present invention include adipic acid, citric acid, malic acid, succinic acid, tartaric acid, ascorbic acid, phosphoric acid, lactic acid, and fumaric acid and their corresponding salts, as well as sodium alginate, polyacrylic acid, sodium carbonate, and sodium bicarbonate. In the context of pH adjusters, the term salt refers to alkali metal salts or alkaline earth metal salts unless otherwise specified.

[0071] The pH of the composition is preferably 3.0 to 5.9, preferably 3.5 to 5.4, and particularly preferably 4.0 to 5.0 (measured at 21°C using a pH meter, Mettler-Toledo SevenCompact S220). Within this range, the compositions used in the present invention are not only particularly stable chemically, physically, and microbiologically, but are also highly suitable for the scalp and hair for medical and cosmetic purposes. Particularly preferred pH values ​​for the compositions used in the present invention are 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, and 5.4.

[0072] According to the present invention, the compositions are applied topically. Topical application means external application, particularly topical external application. The compositions according to the present invention are preferably skin, scalp, and hair care products (i.e., treatments such as shampoos, conditioners, treatments, emulsions, lotions, shower gels, day creams, facial creams, facial liquids, and / or tonics), and not (pure) hair styling products. In other words, the topical compositions of the present invention do not have the primary purpose of hair styling, as their effect acts on the keratinized hair itself and not on the scalp (i.e., metabolically active hair follicles). Rather, the focus is on the medicinal / pharmaceutical or cosmetic treatment of the skin, scalp, and hair.

[0073] In preferred embodiments, the components, particularly the active ingredient dimethylglycine or a salt of dimethylglycine and caffeine, are uniformly dispersed in the aqueous phase in the composition according to the present invention. The term “aqueous phase” includes the possibility of the presence of an organic solvent (e.g., alcohol) that is miscible with water. This means, in particular, that the composition according to the present invention preferably does not have a carrier material. The composition according to the present invention preferably does not contain layered structures (particularly vesicles and / or layered bilayer structures and / or liposomes). The composition according to the present invention also preferably does not contain any material that forms layered structures (particularly vesicles and / or layered bilayer structures).

[0074] In a preferred embodiment, the composition according to the present invention may be in the form of a leave-on formulation or a rinse-off formulation.

[0075] Leave-on formulations are characterized by remaining in contact with the treated (scalp) skin and / or treated hair after application. This creates a kind of active ingredient reservoir that can exhibit its effectiveness over a longer period of time. Leave-on formulations may be formulated, for example, as a hydrogel or emulsion, or as an aqueous solution or water-alcohol solution (tonic). Leave-on formulations are preferably in the form of a slightly viscous formulation, which as a result remains concentrated on the scalp and / or hair and does not spread easily to the hair shaft. However, since these leave-on formulations can leave a somewhat disordered impression, it is important to ensure that the hair is not stressed by the substances that give the formulation its viscosity.

[0076] Rinse-off formulations are characterized in that the components of the composition according to the present invention, to be applied, are washed off again after use. In this way, excessive stress on the scalp and / or hair can be avoided. Rinse-off formulations may preferably exist in the form of shampoos, conditioners, or skin, scalp, and / or hair treatments. In a preferred embodiment, an exposure time of about 2 to 5 minutes should be given to the composition according to the present invention applied as a rinse-off formulation. In this way, the necessary penetration of the active ingredients into the scalp and / or hair follicles is possible.

[0077] The present invention further relates to the use of the compositions of the present invention for treating hair, scalp, and skin.

[0078] In preferred embodiments, treatments of hair and scalp relate to the treatment and / or prevention of hair loss. The term hair loss includes alopecia areata (circular hair loss), male pattern baldness (hereditary hair loss) in women and men, diffuse alopecia (diffuse hair loss), age-related hair loss (hair loss due to aging), and hair loss caused by chemotherapy.

[0079] The type of hair loss treated is preferably hereditary hair loss (androgenetic alopecia).

[0080] The hair loss treated is preferably age-related hair loss (alopecia due to aging).

[0081] In preferred embodiments, the skin treatment relates purely to visual and aesthetic improvements, such as creating smoother and simply more beautiful skin. However, beyond this, cosmetic / medical effects, such as improved protective function and enhanced barrier properties, are also achieved by the present invention. Furthermore, wound healing is improved.

[0082] In other words, the use of the present invention leads to a significant improvement in epidermal barrier function and integrity, improved skin appearance, and increased skin water content. This is related to increased adhesion of the stratum corneum and improved skin barrier homeostasis, ultimately resulting in improved protection against infections (microbial diseases).

[0083] When used in medical applications, the present invention encompasses both therapeutic and preventive treatments for skin diseases. The disorders are preferably susceptibility to microbial skin infections, dermatitis, rough skin, dry skin, skin irritation, itching, pruritus, allergies, psoriasis, psoriatic arthritis, eczema, scleroderma, atopic dermatitis, contact dermatitis, systemic lupus erythematosus, acne, and contact allergies.

[0084] Non-therapeutic (i.e., purely cosmetic) use includes the treatment of cosmetic indications of the skin, particularly selected from rough skin, dry skin, skin irritation, itching, and itching, as well as the prevention of skin infections and the reduction of susceptibility to contact allergies.

[0085] The present invention is illustrated by the following compositions, but is not intended to limit itself to any particular example. Experimental Section

[0086] The following compositions were prepared by homogenization procedures known to those skilled in the art. In each case, the amounts of the components were selected such that their weight proportions in the finished composition corresponded to the weight proportions indicated.

[0087] Example 1 A composition in the form of shampoo (pH 4.8) containing the following ingredients: Millet Sodium Sulfate 4.0% by weight Sodium laureth sulfate 4.0% by weight Sodium laureth disodium sulfosuccinate 3.0% by weight Tocopherol acetate 0.3% by weight Citric acid 0.2% by weight Caffeine 1.0% by weight Sodium dimethylglycine 1.0% by weight Fragrance 0.3% by weight Potassium sorbate 0.2% by weight Sodium benzoate 0.1% by weight Water up to 100% by weight

[0088] Example 2 A composition in the form of a conditioner (pH 4.4) containing the following ingredients: Sodium laureth-11 carboxylate 1.0% by weight (Polyquaternium-4 / Hydroxypropyl Starch) Copolymer 2.0% by weight Steerless-8 5.0% weight Cetyl alcohol 2.0% by weight Fragrance 0.5% by weight Caffeine 0.4% by weight Dimethylglycine Na 0.4% by weight Hydrolyzed creatine 0.5% by weight Citric acid 0.2% by weight Sodium benzoate 0.05% by weight Potassium sorbate 0.15% by weight Water up to 100% by weight

[0089] Example 3 A composition in the form of a hair tonic containing the following ingredients: Denatured alcohol 30.0% by weight Amodimethicone 0.5% by weight Panthenol 0.5% by weight Caffeine 0.5% by weight Dimethylglycine Na 0.5% by weight Bisabolol 0.2% by weight PEG-25 PABA 0.5% by weight PEG-16 (Hydrogenated Castor Oil) 0.5% by weight Fragrance 0.3% by weight Menthol 0.3% by weight Lactic acid 0.1% by weight Water up to 100% by weight

[0090] Example 4 A composition in emulsion form containing the following ingredients: PEG-40 (Hydrogenated Castor Oil) 6.0% by weight Cetearyl alcohol 0.3% by weight Beeswax 0.7% by weight Myristyl myristate 1.0% by weight Hexyldecanol 5.0% by weight Dicapryl ether 4.0% by weight Dioctylcyclohexane 3.0% by weight Tocopherol acetate 1.0% by weight Octyl methoxycinnamate 2.0% by weight 4-Isobutyl-dibenzoylmethane 1.0% by weight Ascorbyl palmitate 0.2% by weight Retinyl palmitate 0.05% by weight 1,4-Butylene glycol 4.0% by weight Carbomer 0.3% by weight Hexyldecanol and hexyldecyl laurate 1.0% by weight Sufficient citric acid (pH 5.5) Caffeine 0.5% by weight Dimethylglycine Na 0.4% by weight Fragrance 0.2% by weight Water up to 100% by weight

[0091] Example 5 A composition in the form of an oil-in-water emulsion containing the following ingredients: Glycerol monostearate 2% by weight Cetyl alcohol 3% by weight Cetyl phosphate 0.4% by weight Paraffin oil, subliquidum 15% by weight Vaseline 3% by weight Triglyceryl caprylate 4% by weight Octyldodecanol 2% by weight Hydrogenated coconut fat 2% by weight Glycerol 3% by weight Glycolic acid (pH 4.0) Caffeine 0.5% by weight Dimethylglycine Na 0.4% by weight Scented oil Sufficient preservatives Water up to 100% by weight

[0092] Example 6 A composition in the form of an oil-in-water emulsion containing the following ingredients: PEG-7 Hydrogenated Castor Oil 4% by weight Wool Fat Alcohol 1.5% by weight Beeswax 3% by weight Triglycerides, liquid, 5% by weight Petrolatum 9% by weight Stearyl alcohol 4% by weight Paraffin oil, Subliquidam 4% by weight Glycerol 2% by weight Magnesium sulfate 7H2O 0.7% by weight Caffeine 0.5% by weight Dimethylglycine Na 0.4% by weight Sufficient lactic acid (pH 5.9) Scented oil Sufficient preservatives Water up to 100% by weight

[0093] Reference Example 1a A shampoo-type composition containing the following ingredients (containing no sodium dimethylglycine or caffeine): Millet Sodium Sulfate 4.0% by weight Sodium laureth sulfate 4.0% by weight Sodium laureth disodium sulfosuccinate 3.0% by weight Tocopherol acetate 0.3% by weight Citric acid 0.2% by weight Fragrance 0.3% by weight Potassium sorbate 0.2% by weight Sodium benzoate 0.1% by weight Water up to 100% by weight

[0094] Reference Example 1b A shampoo-type composition containing the following ingredients (without sodium dimethylglycine) Yes) : Millet Sodium Sulfate 4.0% by weight Sodium laureth sulfate 4.0% by weight Sodium laureth disodium sulfosuccinate 3.0% by weight Tocopherol acetate 0.3% by weight Citric acid 0.2% by weight Caffeine 1.0% by weight Fragrance 0.3% by weight Potassium sorbate 0.2% by weight Sodium benzoate 0.1% by weight Water up to 100% by weight

[0095] Reference Example 1c A shampoo-type composition containing the following ingredients (mosquito (Phenoic acid-free): Millet Sodium Sulfate 4.0% by weight Sodium laureth sulfate 4.0% by weight Sodium laureth disodium sulfosuccinate 3.0% by weight Tocopherol acetate 0.3% by weight Citric acid 0.2% by weight Sodium dimethylglycine 1.0% by weight Fragrance 0.3% by weight Potassium sorbate 0.2% by weight Sodium benzoate 0.1% by weight Water up to 100% by weight

[0096] Study design and results 1. As part of an in vitro study, the effects of caffeine, sodium dimethylglycine, and combinations thereof were investigated in a cell culture model of human keratinizing keratinocyte cells. For this purpose, HaCaT cells were cultured in DMEM medium (containing fetal bovine serum and an antimicrobial-antifungal mixture) for 1, 3, 5, and 7 days. Cell viability, proliferation, and migration were determined, among other things, using suitable measurement methods, and the expression of growth factors related to cell growth was measured.

[0097] Proof of survival This measurement used the so-called MTT assay to determine the metabolic activity of cells as an indicator of cell viability and cytotoxicity. This colorimetric assay is based on the fact that the yellow tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, or MTT) is reduced by metabolically active cells to purple formazan crystals.

[0098] Human epidermal keratinocyte cells (HaCaT) were seeded at a cell density of 5,000 cells / well in 96-well plates and cultured in medium (DMEM containing 10% FBS, 1% penicillin-streptomycin, and 0.5% fungizone). The cell culture medium was diluted with dimethylglycine sodium (DMG) and caffeine (c) at concentrations of the active ingredients at 37°C and 5 vol. % CO2 the day after incubation, and again 24 hours later, as well as 48 and 72 hours later. aff) or without any combination thereof (control), or treated with these. Measurements were performed as in the study previously published in BI Toth, N. Dobrosi, A. Dajnoki, G. Czifra, A. Olah, AG Szollosi, I. Juhasz, K. Sugawara, R. Paus, T. Biro, J Invest Dermatol 2011, 131, 1095-1104.

[0099] Figure 1 shows cell viability at 24, 48, and 72 hours after culture, with an increase observed at 72 hours with the addition of a combination of DMG and caffeine. Cell viability was determined using the MTT assay. Absorption was measured in four consecutive samples and normalized to the control at 24 hours. Mean values ​​are shown along with the standard deviation.

[0100] Evidence of proliferation To measure cell proliferation, a so-called CyQUANT assay was performed. In this fluorescence-based assay, the fluorescent dye used binds to DNA (deoxyribonucleic acid), and the amount of cellular DNA present is a direct measure of the number of cells in the sample.

[0101] Human epidermal keratinocyte cells (HaCaT) were seeded at a cell density of 5,000 cells / well in 96-well plates and cultured in medium (DMEM containing 10% FBS, 1% penicillin-streptomycin, and 0.5% fungizone). Dimethylglycine sodium (DMG) and caffeine (c) were added at concentrations already present after culture at 37°C and 5 vol. % CO2, the following day, 24 hours later, 48 hours later, and 72 hours later. aCell culture media containing ff), or a combination thereof (control), or those containing these were replaced. Measurements were performed as in the study previously published in A. Olah, BI Toth, I. Borbiro, K. Sugawara, AG Szollosi, G. Czifra, B. Pal, L. Ambrus, J. Kloepper, E. Camera, The Journal of Clinical Investigation 2014, 124, 3713-3724.

[0102] Figure 2 shows cell proliferation at 24, 48, and 72 hours after culture, with a clearly disproportionate increase observed at 72 hours with the addition of a combination of DMG and caffeine. Cell proliferation was assessed using the CyQUANT assay. Fluorescence was measured in triplicate and normalized to the control at 24 hours. Mean values ​​are given along with standard deviation.

[0103] Evidence of movement Based on a previously published study by T. Kawabata, T. Otsuka, K. Fujita, G. Sakai, R. Matsushima-Nishiwaki, O. Kozawa, and H. Tokuda in *International Journal of Molecular Medicine* 2018, 42, 3149-3156, a so-called wound healing assay was performed to measure cell migration. The principle is based on measuring the migration of cells to a culture surface that has not yet colonized over time. For this purpose, 20,000 cells were seeded for 48 hours at 37°C and 5 vol. %CO2 in culture medium (5% FBS, 1% penicillin-streptomycin, 0.5% fungizone-containing DMEM) in two adjacent wells or cavities separated by a silicone insert (with a normalized width). The plastic insert was then removed ("creation of a wound"), and cell migration was recorded by determining the culture surface that had not yet colonized by cells over time using images. Simultaneously, in each case, cell culture media containing or without the existing active substance concentrations of DMG and caffeine (control), as well as the combination of DMG and caffeine, were replaced immediately after removal of the plastic insert (0h) and again 24h later. Image evaluation and identification of culture surfaces where cells had not colonized were performed using software (ImageJ).

[0104] Figure 3 shows migration over time and with various concentrations of DMG and caffeine. Migration or wound closure occurred disproportionately faster with the DMG and caffeine combination compared to the control and individual doses of DMG or caffeine. Wounds were created at 0h, and images were taken at 16h, 20h, and 24h from culture. Based on the images, the culture surface that had not colonized by cells was identified using ImageJ software. Measurements were normalized to 0h (maximum wound size) and given as percentages.

[0105] Detection of VEGF gene expression VEGF (vascular endothelial growth factor) promotes the growth and formation of new blood vessels and lymphatic vessels. Gene expression was measured using a standard method known as quantitative real-time PCR (qRT-PCR).

[0106] Human epidermal keratinocyte cells (HaCaT) were seeded at a cell density of 140,000 cells / well in 6-well plates and cultured in medium (DMEM containing 10% FBS, 1% penicillin-streptomycin, and 0.5% fungizone) at 37°C and 5 vol. % CO2. The following day, in each case, the cell culture medium was replaced with one containing or without the already present concentrations of active substances (control), and cells were collected after 24 hours. Gene expression was measured using qRT-PCR, based on a previously published study in BV Diaz, M.-C. Lenoir, A. Ladoux, C. Frelin, M. Demarchez, S. Michel, Journal of Biological Chemistry 2000, 275, 642-650.

[0107] Figure 4 shows the gene expression of VEGF 24 hours after culturing, revealing a significant increase in gene expression upon the addition of DMG combined with caffeine. Relative gene expression determined by VEGF qRT-PCR (determined using triplicate assays, normalized for constitutively expressed genes and the gene expression of GAPDH-glyceraldehyde-3-phosphate dehydrogenase) is shown. The mean value is given along with the standard deviation.

[0108] In summary, surprisingly, the combination of caffeine with DMG had a positive effect on growth-related HaCaT cell parameters, and the expression of the growth factor VEGF was significantly increased compared to HaCaT cell treatment with caffeine or DMG alone.

[0109] 2. As part of a double-blind study using a randomized, placebo-controlled study design, the shampoo according to the present invention of Example 1, as well as the shampoos of Reference Examples 1a, 1b, and 1c, were used for 6 months by men and women with hereditary hair loss. Dermatologically controlled measurements of hair loss rates were performed at baseline and after 6 months, and participants were asked to subjectively assess the reduction in hair loss at the end of application. These results were recorded using questionnaires.

[0110] In Example 1, the subjects who used the shampoo according to the present invention were found to have the most significant reduction in hair loss. This is consistent with the results showing a significantly increased reduction in hair loss rate in the same group of subjects compared to subjects who used one of the three reference shampoos. [Brief explanation of the drawing]

[0111] [Figure 1] Cell viability is shown 24h, 48h, and 72h after culturing. [Figure 2] Cell proliferation after 24, 48, and 72 hours of culture is shown. [Figure 3] This shows the movement over time and using various concentrations of DMG and caffeine. [Figure 4] This shows the gene expression of VEGF 24 hours after culturing.

Claims

1. (A) Dimethylglycine and / or salts of dimethylglycine, (B) Caffeine A topical composition containing the following:

2. The composition according to claim 1, wherein the composition contains 0.001% to 10.0% by weight of dimethylglycine and / or a salt of dimethylglycine.

3. The composition according to claim 1 or 2, wherein the composition contains 0.001% to 3.0% by weight of caffeine.

4. The composition according to any one of claims 1 to 3, wherein the composition contains at least one other active ingredient selected from menthol, biotin, PCA zinc, niacinamide, panthenol, ectoin, ubiquinone-10, taurine, pantolactone, echinacea, carnitine, tocopherol acetate, and combinations thereof.

5. The composition according to any one of claims 1 to 4, wherein the composition contains at least one additive selected from hair conditioning agents, lipid replenishers, preservatives, stabilizers, fragrances, antioxidants, rheology modifiers, thickeners, conditioning agents, pigments, pearlescent agents, whitening agents, solvents, pH adjusters, and combinations thereof.

6. The composition according to any one of claims 1 to 5, wherein the composition is a care composition.

7. The composition according to any one of claims 1 to 6, wherein the composition promotes the metabolism of skin and hair.

8. A composition according to any one of claims 1 to 7 for the treatment of hair, scalp and / or skin.

9. The composition according to claim 8, wherein the treatment for hair and scalp is for the treatment and / or prevention of hair loss, and the treatment for skin is for improving epidermal barrier function and integrity, improving the appearance of the skin, increasing the water content of the skin, and improving wound healing.

10. The composition according to claim 8 or 9, wherein the hair loss is selected from alopecia areata (circular hair loss), male pattern baldness in women and men (hereditary hair loss), diffuse alopecia (diffuse hair loss), age-related hair loss (hair loss due to aging), and hair loss caused by chemotherapy.

11. A composition according to any one of claims 8 to 10, for use as a cosmetic or as a pharmaceutical.

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