Composition comprising phosphinic acid and dimethylglycine

Abstract

The present invention relates to a composition comprising phosphinic acid or a salt thereof and dimethylglycine or a salt thereof, in particular in a dosage form for oral or topical administration. Furthermore, the present invention relates to the (cosmetic and / or medical) use of this composition for improving the condition of the hair and / or skin, promoting hair and / or skin metabolism, promoting hair growth, and / or treating and / or preventing hair loss. Furthermore, the present invention relates to a dietary supplement for promoting hair and / or skin metabolism and / or promoting hair growth and / or treating and / or preventing hair loss.Furthermore, the invention relates to a kit comprising dimethylglycine and / or a salt of dimethylglycine and phosphinic acid and / or at least one salt of phosphinic acid, wherein the two compounds are present in separate administration forms.

Description

The present invention relates to a composition comprising phosphinic acid or a salt thereof and dimethyl glycine or a salt thereof, in particular in a dosage form for oral or topical administration. The present invention also relates to the (cosmetic and / or medical) use of this composition for improving the state of the hair and / or of the skin, for promoting the metabolism of the hair and / or of the skin, for promoting hair growth and / or for treating and / or preventing hair loss. The present invention further relates to a food supplement for promoting the metabolism of the hair and / or of the skin and / or for promoting hair growth and / or for treating and / or preventing hair loss.Human hair has lost its importance as a protective function for the body in the meantime to a great extent. However, healthy hair has a great cultural importance worldwide for women and men and is frequently considered to be signs of well-being and health. Consequently, bulkier hair caused by hair loss, for example, often adversely affects the quality of life.The causes of hair loss are manifold and range from age-related hair loss via genetically or hormonally caused disorders, autoimmune disorders, metabolic disorders, including malnutrition, to infections, trauma, tumors and medicaments such as cytostatic agents and anticoagulants.Hair loss caused by hormones such as androgens is referred to as androgenetic alopecia (alopecia androgenetica or also AGA) and is also considered to be the most common cause of hair loss in men, but also in women in particular. In this case, it is possible to distinguish between male and female hair loss patterns. Other common forms of non-scarring alopecia include telogues effluvium (TE), diffuse hair loss, and acutely onset inflammatory circular hair loss, also referred to as alopecia areata (AA).The influence of nutrient deficiency on the hair structure and the hair growth is quite considerable. Effects on hair growth include acute telogous effluvium (TE), a known consequence of sudden weight loss or decreased protein input, and diffuse alopecia which occurs in niacin deficiency. Studies have also reported possible relationships between nutrient deficiency and chronic TE, androgenetic alopecia (AGA), female hair loss (FPHL) and alopecia areata (AA) (Guo E. L., Kata R. Diet and hair loss: effects of nutrient deficiency and supplement use. Dermatol Pract Concept. 2017; 7(1):1).Micronutrients such as vitamins and minerals play an important, but not quite clear role for the normal development of hair follicles and the function of immune cells. Accordingly, there is evidence in numerous studies of a relationship between hair loss and micronutrient deficiency.An overview of the role of vitamins and minerals such as vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, iron, selenium and zinc in non-scarring alopecia is given by Almohanna et al. (Almohanna, Hind M et al. "The Role of Vitamins and Minerals in Hair Loss: A Review." Dermatology and therapy vol. 9.1 (2019): 51-70).Guo and Kata describe the study situation with regard to a deficiency or supplementation with iron, zinc, niacin, fatty acids, selenium, vitamin D, vitamin A, vitamin E, folic acid, biotin, amino acids and proteins as well as antioxidants.Similarly, a review by Goldberg and Lenzy deals with changes in hair due to general malnutrition and lack of micronutrients in certain groups of patients (Goldberg, L.J., Lenzy, Y. Nutrition, and hair. Clin Dermatol. 2010 Jul-Aug; 28(4):412-9).A possible role of dietary supplements such as amino acids, vitamins and trace elements, essential fatty acids, coenzymes Q and A, bioflavinonoids, inositol, methylsulfonylmethane (MSM), dimethyl glycine (DMG), silicic acid, celp, green tea extract, saw palm extract and grape seed extract in preventing hair loss is finally described in a review article by Jain et al. (Jain, Pushpendra & Joshi, Himanshu & Das, Debajyoti. (2012). Drug that Coffees Hair Loss and Promotes Hair Growth-A Review. International Journal of Research in Pharmaceutical and Biomedical Sciences. 3. 1476-82).A deficiency of such micronutrients could be a variable risk factor for the development, prevention and treatment of alopecia.While food supplements containing vitamins and minerals are relatively inexpensive and easily accessible, their use presupposes, however, which vitamins and minerals are helpful in the treatment of hair loss. However, to date, only a few studies have been conducted to examine the effect of micronutrient supplementation on hair growth in micronutrient-deficient and alopecia patients to establish a relationship between hair loss and micronutrient deficiency, and there is much less literature on the effects of supplementation in non-nutritional individuals.In addition, there are indications that an overdosage of certain micronutrients, such as vitamin A, vitamin E or selenium, can even promote hair loss (Almohanna et al.; Guo and Catta).In summary, dietary supplements can have both positive and negative effects on hair loss, and if no nutritional deficiency is detected, there is little evidence of what type of supplementation is suitable to restore hair growth or prevent further hair loss.In addition, there are few allowed pharmaceutical treatment possibilities for hair loss to date, such as androgenetic alopecia, and the already existing treatment possibilities are either not sufficiently effective or are associated with unpleasant side effects. Similarly, it is unpleasant to see, for example, Alopecia areata in treatment possibilities for the acutely employed inflammatory circular hair loss, and for hair loss caused by other causes.There is thus still a need for improved treatment methods, in particular a need for compositions which can be used orally and / or topically against hair loss, wherein these compositions should show no side effects or only negligible side effects. In particular, there is a need for food supplement compositions which are readily available and can be applied straightforwardly. Also, there is a need for compositions which are pharmaceutical in nature and do not exhibit side effects or which are cosmetic in nature.Proceeding from this, it was the object of the present invention to provide a well-tolerated composition for the treatment of hair and skin, in particular for the prevention and / or treatment of hair loss. Furthermore, this composition should be orally and / or topically applicable and overcome the disadvantages of the compositions known from the prior art.According to the invention, the object is achieved by providing a composition which comprises a) phosphonic acid and / or at least one salt of phosphinic acid, and b) dimethylglycine and / or a salt of dimethylglycine.Phosphinic acid, also hypophosphorous acid, is one of the acids of phosphorus and has the empirical formula H 3 PO 2. Their salts are called phosphinates or hypophosphites. Monovalent and / or divalent salts of phosphinic acid are preferred according to the invention. A preferred monovalent salt is sodium hypophosphite (also sodium phosphinate) (Na(H 2 PO 2)). Particular preference is given to divalent salts of phosphinic acid, particular preference again being given to calcium hypophosphite (Ca(H 2 PO 2)2).The composition according to the invention preferably comprises hypophosphite and in particular calcium hypophosphite in an amount of from 0.0001 to 35.0 percent by weight (wt %), preferably from 0.001 to 25.0% by weight, more preferably 0.01 to 15.0% by weight, even more preferably 0.1 to 10.0% by weight, particularly preferably 0.1 to 5.0% by weight, based in each case on the total weight of the composition.In a preferred embodiment of the invention, the composition according to the invention may comprise 0.0001% by weight, 0.001% by weight, 0.01% by weight, 0.1% by weight, 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, 20% by weight, 25% by weight or 35% by weight of phosphinic acid and / or a salt of phosphinic acid, in each case based on the total weight of the composition.It has surprisingly been found that the composition according to the invention with dimethyl glycine and / or a salt thereof and phosphonic acid and / or a salt thereof has an excellent effectiveness in the treatment of hair loss, in particular hereditary and age-related hair loss. In addition, the composition is particularly medicinally compatible.Dimethyl glycine (N,N-dimethyl glycine) occurs in plants, animals and humans, with only very small amounts of dimethyl glycine being formed in humans. In a multistage biosynthesis of glycine from choline, it is formed as intermediate by transamination of betaine with betaine-homopolycysteine methylase.N,N-dimethylglycine, also (dimethylamino)acetic acid, is represented by the following chemical formula 1: According to the present invention, it has surprisingly been found that dimethylglycine and / or a salt of dimethylglycine is not only suitable for topical application, but is also excellently suitable, in combination with phosphonic acid and / or at least one salt of phosphinic acid as an oral preparation, for improving the state of the hair and skin, in particular for treating or preventing hair loss.According to the invention, not only is the use of dimethyl glycine used, but also of its salts, solvates and hydrates. These are preferably pharmaceutically or cosmetically acceptable salts of dimethyl glycine. The salt is particularly preferably a water soluble salt having a solubility in water of at least 10 g / l at 20°C.In a preferred embodiment, the salt of dimethyl glycine is an alkali, alkaline earth or ammonium salt of dimethyl glycine.Examples are sodium, potassium, calcium, magnesium and ammonium salts. In the ammonium salts, the ammonium cation carries one to four alkyl groups each having, independently of one another, 1 to 4 carbon atoms. Preferred are the sodium and potassium salt of dimethyl glycine, especially the sodium salt of dimethyl glycine, namely sodium dimethyl glycinate (sodium N,N-dimethyl glycinate).In an alternatively preferred embodiment, the salt of dimethyl glycine may be the salt of an inorganic acid with dimethyl glycine.Examples of salts of dimethyl glycine with an inorganic acid are the hydrochloride, hydrobromide, hydroiodide, hydrogen sulfate, sulfate, hydrogen sulfite, sulfite, hydrogen carbonate, carbonate, monophosphate, diphosphate and triphosphate of dimethyl glycine, and mixtures thereof. The hydrochloride of dimethyl glycine, namely dimethyl glycine hydrochloride (N,N-dimethyl glycine hydrochloride), is particularly preferred.According to the invention, the dimethyl glycine and / or salt of dimethyl glycine is preferably selected from the group consisting of dimethyl glycine, sodium dimethyl glycinate and dimethyl glycine hydrochloride.According to the invention, the dimethyl glycine and / or salt of dimethyl glycine is preferably selected from the group consisting of dimethyl glycine, sodium dimethyl glycinate and dimethyl glycine hydrochloride.It is believed that the (head) skin is maintained and reinforces the skin barrier. Thus, according to the invention, a distinct hair root- and (head) skin-strengthening effect is achieved, in particular in the treatment of skin which has died or weakened due to the age or the age, as well as hair loss, such as the hair loss due to the hereditary and age.The composition according to the invention contains dimethyl glycine and / or a salt of dimethyl glycine preferably in a proportion of 0.0001 to 35.0 percent by weight (wt %), preferably of 0.001 to 25.0 wt %, more preferably 0.01 to 15.0 wt %, even more preferably 0.1 to 10.0 wt %, particularly preferably 0.1 to 5.0 wt %, in each case based on the total weight of the composition. In a preferred embodiment of the invention, the composition according to the invention may comprise 0.0001% by weight, 0.001% by weight, 0.01% by weight, 0.1% by weight, 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, 20% by weight, 25% by weight or 35% by weight of dimethylglycine and / or a salt of dimethylglycine, in each case based on the total weight of the composition.Preferably, the composition according to the invention contains dimethyl glycine and / or a salt of dimethyl glycine as a chemical pure substance, including the respective solvates and hydrates (e.g. the dihydrate of sodium dimethyl glycinate), since the purity of the composition can thus be increased and the occurrence of undesired side effects can be reduced.The composition according to the invention contains dimethyl glycine and / or a salt thereof and also phosphonic acid and / or a salt thereof preferably in a molar ratio of 1:10 to 10:1, preferably 1:5 to 5:1, m particularly preferably 1:2 to 2:1.In a preferred embodiment, the composition according to the invention comprises at least one further active ingredient c), wherein the at least one further active ingredient is selected from amla extract, β-carotene, biotin, carnitine, curcumin, echinacea, ectoin, iron, folic acid, pomegranate extract, green tea extract, millet extract, millet oil, pumpkin seed oil, creatine, L-cysteine, L-lysine, niacin, niacinamide, pantolactone, panthothenoic acid, piperine, procyanidin, rosemary extract, saw palm extract, horsetail extract, selenium, silicon, taurine, tocopheryl acetate, tomato extract, Ubiquinone-10, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin E, zinc and combinations thereof, in particular selected from zinc, biotin, millet extract, selenium and combinations thereof.Amla extract is an extract from Indian Stankberry (Phyllanthus emblica). Amla extract may be contained in the composition according to the invention in an amount of 0.1-50.0% by weight, preferably 1-30% by weight, more preferably 5-25% by weight, in each case based on the total weight of the composition.β-Carotene is a precursor of vitamin A and is therefore also referred to as provitamin A. In the composition according to the invention, β-carotene can be present in an amount of 0.01-1.0% by weight, preferably 0.05-0.5% by weight, in each case based on the total weight of the composition.Biotin, also referred to as vitamin B7or vitamin H, is a water soluble vitamin from the B complex. Biotin can further reduce hair loss and strengthen the skin according to the invention. Biotin may be present in the composition according to the invention in an amount of 0.001-10.0% by weight, preferably 0.005-1.0% by weight, based in each case on the total weight of the composition.Carnitine can be contained in the composition according to the invention in an amount of 0.001 wt.% to 10.0 wt.%, preferably 0.005 wt.% to 7.50 wt.%, based in each case on the total weight of the composition.Curcumin may be contained in the composition according to the invention in an amount of 0.1-20.0 wt. %, preferably 1-15 wt. %, in each case based on the total weight of the composition.Echinacea can excite the blood circulation of the scalp and thus supply the hair follicles with oxygen- and nutrient-rich blood, which has a further stabilizing effect on the hair and in particular on the hair root. Echinaceamay be present in the composition according to the invention in an amount of 0.001% by weight to 10.0% by weight, preferably 0.005% by weight to 7.50% by weight, in each case based on the total weight of the composition.Ectoin is a cyclic amino acid and, according to the invention, further stabilizes the natural structure of hair. In the composition according to the invention, ectoin can be present in an amount of from 0.001% by weight to 10.0% by weight, preferably from 0.005% by weight to 7.50% by weight, in each case based on the total weight of the composition.Iron can be contained in the composition according to the invention in an amount of 0.01-1.0% by weight, preferably 0.05-0.5% by weight, in each case based on the total weight of the composition.Folic acid can be contained in the composition according to the invention in an amount of 0.001-1.0% by weight, preferably 0.05-0.5% by weight, in each case based on the total weight of the composition.In the composition according to the invention, pomegranate extract may be contained in an amount of 0.1-20.0 wt.%, preferably 1-15 wt.%, in each case based on the total weight of the composition.In the composition according to the invention, green tea extract can be used in an amount of 0.1-10.0% by weight, preferably 1.0-5.0% by weight, in each case based on the total weight of the composition.Millet extract may be present in the composition according to the invention in an amount of 0.01-40.0 wt. %, preferably 1-35 wt. %, more preferably 5-30 wt. %, in each case based on the total weight of the composition.The composition according to the invention may comprise millet oil in an amount of 0.01-30.0% by weight, preferably 1-15% by weight, based in each case on the total weight of the composition.In the composition according to the invention, pumpkin core oil may be present in an amount of 0.1-20.0% by weight, preferably 1-15% by weight, in each case based on the total weight of the composition.In the composition according to the invention, creatine can be present in a quantity of from 0.001% by weight to 10.0% by weight, preferably from 0.005% by weight to 7.50% by weight, based in each case on the total weight of the composition.In the composition according to the invention, L-cysteine can be present in an amount of 0.01-20.0% by weight, preferably 0.1-1.0% by weight, in each case based on the total weight of the composition.In the composition according to the invention, L-lysine can be present in an amount of 0.1-20.0% by weight, preferably 1-15% by weight, in each case based on the total weight of the composition.Niacin can be present in the composition according to the invention in an amount of 0.1-10.0 wt. %, preferably 0.5-5.0 wt. %, in each case based on the total weight of the composition.Niacinamide (also nicotinamide) is the amide of nicotinic acid and is also referred to as vitamin B3. Among other properties such as a reduction in oxidative stress, niacinamide has a hair growth stimulating effect according to the present invention. Niacinamide can be present in the composition according to the invention in a quantity of 0.001% by weight to 10.0% by weight, preferably 0.005% by weight to 7.50% by weight, based in each case on the total weight of the composition.Pantolactone originates from the group of substituted lactones and, according to the invention, further stimulates the growth factors of the hair roots. Pantolactone can be present in the composition according to the invention in a quantity of from 0.001% by weight to 10.0% by weight, preferably from 0.005% by weight to 7.50% by weight, based in each case on the total weight of the composition.In the composition according to the invention, panthenol acid can be contained in an amount of 0.01-10.0 wt. %, preferably 0.1-2.0 wt. %, in each case based on the total weight of the composition.Piperine may be present in the composition according to the invention in an amount of 0.01-5.0% by weight, preferably 0.05-2.0% by weight, based in each case on the total weight of the composition.Procyanidin may be present in the composition according to the invention in an amount of 0.1-20.0% by weight, preferably 1-15% by weight, in each case based on the total weight of the composition.Rosemary extract may be present in the composition according to the invention in an amount of 0.001-20.0% by weight, preferably 0.01-5.0% by weight, based in each case on the total weight of the composition.Saw palm extract may be contained in the composition according to the invention in an amount of 0.1-20.0 wt. %, preferably 1-15 wt. %, in each case based on the total weight of the composition.In the composition according to the invention, horse-straw extract can be contained in an amount of 0.01-1.0% by weight, preferably 0.1-1.0% by weight, in each case based on the total weight of the composition.Selenium can be contained in the composition according to the invention in an amount of 0.0001-0.5 wt. %, preferably 0.001-0.01 wt. %, in each case based on the total weight of the composition.Silicon (silicas) can be present in the composition according to the invention in an amount of 0.01-10.0% by weight, preferably 0.1-5.0% by weight, based in each case on the total weight of the composition.Taurine or 2-aminoethanesulfonic acid also acts as antioxidant according to the invention in a further stabilizing manner on the skin and hair and in particular on the hair root. Taurine can be contained in the composition according to the invention in a quantity of 0.001 wt. % to 10.0 wt. %, preferably 0.005 wt. % to 7.50 wt. %, based in each case on the total weight of the composition.Tocopheryl acetate exhibits antioxidant properties and according to the invention has a further stabilizing effect on the skin and the hair and in particular on the hair root. The composition according to the invention may comprise tocopheryl acetate from 0.001% by weight to 10.0% by weight, preferably from 0.005% by weight to 7.50% by weight, based in each case on the total weight of the composition.Tomato extract can be contained in the composition according to the invention in an amount of 0.1-20.0 wt. %, preferably 1-15 wt. %, in each case based on the total weight of the composition.Ubiquinone-10 (Q10 or coenzyme Q10) is a quinone derivative. The Q10 belonging to the ubiquinone pool is considered to be an antioxidant and according to the invention has a stabilizing effect on the skin and hair and in particular on the hair root. Ubiquinone-10 can be contained in the composition according to the invention in a quantity of 0.001 wt. % to 10.0 wt. %, preferably 0.005 wt. % to 7.50 wt. %, in each case based on the total weight of the composition.Vitamin B1 (thiamine) can be present in the composition according to the invention in an amount of 0.01-5.0% by weight, preferably 0.05-1.0% by weight, in each case based on the total weight of the composition.Vitamin B2 (riboflavin) can be present in the composition according to the invention in an amount of 0.01-5.0% by weight, preferably 0.05-1.0% by weight, based in each case on the total weight of the composition.Vitamin B6 can be present in the composition according to the invention in an amount of 0.01-5.0% by weight, preferably 0.05-0.5% by weight, based in each case on the total weight of the composition.Vitamin B12may be present in the composition according to the invention in an amount of 0.00001-0.01 wt %, preferably 0.00005-0.0005 wt %, based in each case on the total weight of the composition.Vitamin C can be present in the composition according to the invention in an amount of 0.1-20.0% by weight, preferably 1-15% by weight, based in each case on the total weight of the composition.Vitamin E can be present in the composition according to the invention in an amount of 0.01-10.0% by weight, preferably 0.1-5.0% by weight, in each case based on the total weight of the composition.Zinc can be added as substance with antimicrobial action to the composition according to the invention in an amount of 0.01-30.0% by weight, preferably 0.1-5.0% by weight, in each case based on the total weight of the composition.According to the invention, the composition is applied orally and / or topically. Oral application is understood to mean internal application, in particular by tablets or capsules. "Topical" describes external, generally topical, application.In a preferred embodiment, the composition according to the present invention is a food supplement, in particular a food supplement for promoting the metabolism of the hair and / or skin and / or for promoting hair growth and / or for treating and / or preventing hair loss.Compositions according to the invention, in particular for food supplements, are preferably in the form of capsules, lozenges, tablets, pills and other similar dosage forms, powder bags, liquid vials, bottles with drip liner and similar dosage forms of liquids and powders for receiving the product.In a preferred embodiment, the composition according to the invention comprises in particular a) dimethyl glycine and b) calcium hypophosphite and optionally at least one further active ingredient c) as defined herein.In a preferred embodiment, the constituents, a) dimethylglycine and / or a salt of dimethylglycine, in particular dimethylglycine, b) phosphonic acid and / or at least one salt of phosphinic acid, in particular calcium hypophosphite, c) are optionally at least one further active compound as defined herein, and optionally comprise one or more suitable carrier(s) (d) and / or one or more filler(s) (e).Suitable carriers (d) include, but are not limited to, vegetable oils such as coconut oil, soybean oil, soybean lecithin, sunflower oil, olive oil, palm oil, rapeseed oil and linseed oil; beeswax; sugar alcohols such as sorbitol, mannitol, isomalt, maltitol, lactitol, xylitol and erythritol; monosaccharides such as dextrose (glucose), mannose, fructose; disaccharides such as maltose; and nondigestible carbohydrates such as cellulose and pectins.According to the invention, one or more vegetable oil(s) are preferably used as carrier in capsules. For tablets, one or more sugars or sugar alcohols, preferably xylitol, are preferably used.Suitable fillers (e) are known to the skilled worker. They are used in particular in the production of oral administration forms such as tablets or capsules with small amounts of active compound in order to ensure a size or mass of the tablet required for the production. Preferred fillers are starch or its constituents amylopectin and amylose and / or amylodextrin.Starch is a natural constituent of potatoes, manioc, cereals (e.g. wheat, corn, rice) and legumes (e.g. peas, lentils, white or red beans, chick peas). According to the invention, corn, potato, wheat, rice and / or millet starch is particularly preferred.Amylopectin refers to a polysaccharide from α-D-glucose monomers that can form highly branched structures. The α-D-glucose monomers are here linked to one another in α-1,4-glycosidic terms.Amylose refers to a polysaccharide of α-D-glucose monomers forming linear chains of helical structure. Amylose has a molar mass of between 100,000 and 1,000,000 g / mol, corresponding to about 1000 α-D-glucose monomers (in cereal starches) to 4500 α-D-glucose monomers (in potato starches) linked together α-1,4-glycosidically. At high molar masses, isolated α-1,6-glycosidic branches also occur.Amylodextrin is a conversion product of the starch by dilute acids. Amylodextrin (6C 6 H 10 O 5+ 2 H 2 O) is a compound isomeric to the starch. Amylodextrin can also be recovered as the final product of hydrolysis of amylopectin by β-amylase.The composition of the invention may be in any dosage form suitable for oral or topical administration. Oral forms of administration are preferred. The composition can accordingly be present in a liquid, solid or semi-solid dosage form.Liquid dosage forms include solutions, emulsions, suspensions and syrups. If the composition according to the invention is liquid or semi-solid, it preferably has a pH of between 3.0 and 9.0. The pH is preferably in the range from 4.0 to 8.0, in particular between 5.0 and 7.0.The pH can be adjusted by pH regulators. pH regulators are substances which can adjust a specific pH range, preferably a range from pH 5.5 to 8.0. Examples of pH regulators are acetic acid, acetates, lactic acid, lactates, malic acid, malates, fumaric acid, citric acid, citrates, tartaric acid, tartrates, orthophosphates, di-, tri- and polyphosphates, hydrochloric acid, chlorides, sulphuric acid, sulfates, hydroxides, oxides, adipic acid, adipates, gluconic acid, gluconates, phosphoric acid, calcium carbonate or a hydrate thereof. A preferred example of a pH regulator that can be added when a lower pH is desired is phosphoric acid (H 3 PO 4).Semi-solid dosage forms include, for example, gels, pastes, ointments and creams.Solid dosage forms include tablets, coated tablets, capsules, granules and powders for ingestion. Solid dosage forms can be produced with modified active ingredient release (for example prolonged or delayed).According to the invention, a dosage form of the composition is preferably compressed as a tablet or in a capsule, e.g. a hard gelatin capsule or soft gelatin capsule.The composition of the invention can be prepared by any of the methods known to those skilled in the art.The present invention further relates to the use of the composition according to the invention for improving the state of the hair and / or of the skin and / or for promoting the metabolism of the hair and / or of the skin and / or for promoting hair growth and / or for treating and / or preventing hair loss.The term hair loss includes alopecia areata (circular hair loss), alopecia androgenetica (hereditary hair loss) in women and men, diffuse alopecia (diffuse hair loss), age-related hair loss (senescent alopecia) and chemotherapy-related hair loss.Particular preference is given to the hair loss to be treated as a hereditary hair loss (Alopecia androgenetica).Likewise particularly preferred is the hair loss to be treated, age-related hair loss (senescent alopecia).The use is in particular a cosmetic or medical use.The use according to the invention surprisingly led not only to a reduction in daily hair loss, but also to an increase in hair density and positive effects on hair root activity compared to a control group, wherein the hair density and the hair root activity were determined by established standard methods from the dermatology sector before and after ingestion (see, inter alia, Serrano-Falcon C, Fernandez-Pugnaire MA, Serrano-Ortega S. Hair and scalp evaluation: the trichogram).A further aspect of the present invention relates to a kit comprising a) dimethyl glycine and / or a salt of dimethyl glycine, in particular dimethyl glycine, b) phosphonic acid and / or at least one salt of phosphinic acid, in particular calcium hypophosphite, wherein a) and b) are present in separate administration forms.A) and b) may be for oral and / or topical administration. Both active ingredients can be administered, for example, in the form of a tablet. However, it is also possible to administer one active ingredient as a tablet and the corresponding other active ingredient topically, for example in the form of a cream, lotion, suspension or shampoo base. The two forms of administration can be taken simultaneously or in a manner offset in time from one another. Thus, for example, it is possible to take a tablet comprising one of the active ingredients in the morning and a tablet comprising the corresponding other active ingredient in the evening. Likewise, a lotion comprising one active ingredient can be applied topically in the morning and a tablet comprising the corresponding other active ingredient can be taken in the evening.The invention is intended to be illustrated by the following compositions, but without wishing to restrict it to the specific examples.ExamplesThe following compositions were prepared by means known to those skilled in the art. The amount of the components was chosen in each case such that their proportion by weight in the premix corresponds to the stated proportions by weight.Example 1A composition in the form of a tablet containing the following components: <row><cell>Vitamin C< / cell><cell>80< / cell><cell>8,6< / cell>< / row><row><cell>Vitamin E (α-tocopherol)< / cell><cell>5< / cell><cell>0,5< / cell>< / row><row><cell>Vitamin B2< / cell><cell>1< / cell><cell>0,1< / cell>< / row><row><cell>Vitamin B12< / cell><cell>0,002< / cell><cell>0,0002< / cell>< / row><row><cell>Zinc< / cell><cell>15< / cell><cell>1,6< / cell>< / row><row><cell>Panthothenic acid< / cell><cell>10< / cell><cell>1,1< / cell>< / row><row><cell>Biotin / vitamin H< / cell><cell>0,1< / cell><cell>0,01< / cell>< / row><row><cell>Folic acid< / cell><cell>0,2< / cell><cell>0,02< / cell>< / row><row><cell>Silicon Silicon< / cell><cell>10< / cell><cell>1,1< / cell>< / row><row><cell>L-Cysteine< / cell><cell>5< / cell><cell>0,5< / cell>< / row><row><cell>Millet extract< / cell><cell>300< / cell><cell>32,4< / cell>< / row><row><cell>L-Lysine< / cell><cell>100< / cell><cell>10,8< / cell>< / row><row><cell>Na-N, N-dimethylglycinate< / cell><cell>200< / cell><cell>21,6< / cell>< / row><row><cell>Calcium hypophosphite< / cell><cell>200< / cell><cell>21,6< / cell>< / row><p xml:id="_d905260188" n="0107">The tablet may further contain conventional excipients such as sugar alcohol and / or fillers.<head xml:id="_d905260189">Example 2< / head><p xml:id="_d905260190" n="0108">A composition in the form of a tablet containing the following components:<title desc="title" / ><row><cell>Vitamin C< / cell><cell>80< / cell><cell>8,2< / cell>< / row><row><cell>Vitamin E (α-tocopherol)< / cell><cell>5< / cell><cell>0,5< / cell>< / row><row><cell>Vitamin B2< / cell><cell>1< / cell><cell>0,1< / cell>< / row><row><cell>Vitamin B12< / cell><cell>0,002< / cell><cell>0,0002< / cell>< / row><row><cell>Zinc< / cell><cell>15< / cell><cell>1,5< / cell>< / row><row><cell>Panthothenic acid< / cell><cell>10< / cell><cell>1,0< / cell>< / row><row><cell>Biotin / vitamin H< / cell><cell>0,1< / cell><cell>0,010< / cell>< / row><row><cell>Folic acid< / cell><cell>0,2< / cell><cell>0,02< / cell>< / row><row><cell>Silicon Silicon< / cell><cell>10< / cell><cell>1,0< / cell>< / row><row><cell>L-Cysteine< / cell><cell>5< / cell><cell>0,5< / cell>< / row><row><cell>Millet extract< / cell><cell>300< / cell><cell>30,7< / cell>< / row><row><cell>L-Lysine< / cell><cell>100< / cell><cell>10,2< / cell>< / row><row><cell>Na-N, N-dimethylglycinate< / cell><cell>300< / cell><cell>30,7< / cell>< / row><row><cell>Calcium hypophosphite< / cell><cell>150< / cell><cell>15,4< / cell>< / row><p xml:id="_d905260255" n="0109">The tablet may further contain conventional excipients such as sugar alcohol and / or fillers.<head xml:id="_d905260256">Example 3< / head><p xml:id="_d905260257" n="0110">A composition in the form of a capsule containing the following components:<title desc="title" / ><row><cell>Vitamin C< / cell><cell>100< / cell><cell>21,6< / cell>< / row><row><cell>Vitamin E (α-tocopherol)< / cell><cell>10< / cell><cell>2,2< / cell>< / row><row><cell>Niacin< / cell><cell>18< / cell><cell>3,9< / cell>< / row><row><cell>Zinc< / cell><cell>5< / cell><cell>1,1< / cell>< / row><row><cell>β-Carotene / provitamin A< / cell><cell>2< / cell><cell>0,4< / cell>< / row><row><cell>Vitamin B6< / cell><cell>1,8< / cell><cell>0,4< / cell>< / row><row><cell>Vitamin B2 (riboflavin)< / cell><cell>1< / cell><cell>0,2< / cell>< / row><row><cell>Vitamin B1 (thiamine)< / cell><cell>1,2< / cell><cell>0,3< / cell>< / row><row><cell>Folic acid< / cell><cell>0,3< / cell><cell>0,1< / cell>< / row><row><cell>Biotin< / cell><cell>0,12< / cell><cell>0,03< / cell>< / row><row><cell>Selenium Selenium< / cell><cell>0,03< / cell><cell>0,01< / cell>< / row><row><cell>Vitamin B12< / cell><cell>0,001< / cell><cell>0,0002< / cell>< / row><row><cell>N,N-dimethylglycine hydrochloride< / cell><cell>162< / cell><cell>35,0< / cell>< / row><row><cell>Calcium hypophosphite< / cell><cell>162< / cell><cell>35,0< / cell>< / row><p xml:id="_d905260322" n="0111">The capsule may also contain customary excipients, such as vegetable oil, and / or fillers.<head xml:id="_d905260323">Example 4< / head><p xml:id="_d905260324" n="0112">A composition in the form of a capsule containing the following components:<title desc="title" / ><row><cell>Biotin< / cell><cell>1< / cell><cell>0,03< / cell>< / row><row><cell>Vitamin C< / cell><cell>100< / cell><cell>3,0< / cell>< / row><row><cell>Vitamin E (α-tocopherol)< / cell><cell>6< / cell><cell>0,2< / cell>< / row><row><cell>Zinc< / cell><cell>15< / cell><cell>0,4< / cell>< / row><row><cell>Selenium Selenium< / cell><cell>0,2< / cell><cell>0,01< / cell>< / row><row><cell>Iron iron is iron< / cell><cell>8< / cell><cell>0,2< / cell>< / row><row><cell>Sawpalme extract< / cell><cell>400< / cell><cell>11,9< / cell>< / row><row><cell>Mockhalm extract< / cell><cell>20< / cell><cell>0,6< / cell>< / row><row><cell>Amla extract< / cell><cell>600< / cell><cell>17,8< / cell>< / row><row><cell>Pumpkin's Oil< / cell><cell>300< / cell><cell>8,9< / cell>< / row><row><cell>Procyanidinin< / cell><cell>200< / cell><cell>5,9< / cell>< / row><row><cell>Green tea extract< / cell><cell>100< / cell><cell>3,0< / cell>< / row><row><cell>Rosemary extract< / cell><cell>2< / cell><cell>0,1< / cell>< / row><row><cell>Curcumin< / cell><cell>300< / cell><cell>8,9< / cell>< / row><row><cell>Piperin< / cell><cell>5< / cell><cell>0,1< / cell>< / row><row><cell>Pomegranate extract< / cell><cell>400< / cell><cell>11,9< / cell>< / row><row><cell>Millet oil< / cell><cell>300< / cell><cell>8,9< / cell>< / row><row><cell>L-Cysteine< / cell><cell>10< / cell><cell>0,3< / cell>< / row><row><cell>L-Lysine< / cell><cell>200< / cell><cell>5,9< / cell>< / row><row><cell>N,N-dimethylglycine hydrochloride< / cell><cell>100< / cell><cell>3,0< / cell>< / row><row><cell>Calcium hypophoshite< / cell><cell>300< / cell><cell>8,9< / cell>< / row><p xml:id="_d905260417" n="0113">The capsule may also contain customary excipients, such as vegetable oil, and / or fillers.<head xml:id="_d905260418">Example 5< / head><p xml:id="_d905260419" n="0114">A composition in the form of a shampoo comprising the following components:<title desc="title" / ><row><cell>Sodium Myrethsulfate< / cell><cell>4,0 % by weight< / cell>< / row><row><cell>Sodium laureth sulfate< / cell><cell>4,0 % by weight< / cell>< / row><row><cell>Disodium laurethsulfosuccinate< / cell><cell>3,0 % by weight< / cell>< / row><row><cell>Tocopheryl acetate< / cell><cell>0,3 % by weight< / cell>< / row><row><cell>Citric acid< / cell><cell>1,0 % by weight< / cell>< / row><row><cell>Calcium hypophosphite< / cell><cell>0,5 % by weight< / cell>< / row><row><cell>Na-N, N-dimethylglycinate< / cell><cell>1,0 % by weight< / cell>< / row><row><cell>Perfume< / cell><cell>0,3 % by weight< / cell>< / row><row><cell>Potassium sorbate< / cell><cell>0,2 % by weight< / cell>< / row><row><cell>Sodium benzoate< / cell><cell>0,1 % by weight< / cell>< / row><row><cell>Water< / cell><cell>ad 100% by weight< / cell>< / row><head xml:id="_d905260460">Example 6< / head><p xml:id="_d905260461" n="0115">A composition in the form of a hair water which contains the following components:<title desc="title" / ><row><cell>Alcohol denate.< / cell><cell>30,0 % by weight< / cell>< / row><row><cell>Amodimethicone< / cell><cell>0,5 % by weight< / cell>< / row><row><cell>Panthenol< / cell><cell>0,5 % by weight< / cell>< / row><row><cell>Calcium hypophosphite< / cell><cell>0,25 % by weight< / cell>< / row><row><cell>N,N-dimethylglycine hydrochloride< / cell><cell>0,25 % by weight< / cell>< / row><row><cell>Bisabolol< / cell><cell>0,2 % by weight< / cell>< / row><row><cell>PEG-25 PABA< / cell><cell>0,5 % by weight< / cell>< / row><row><cell>PEG-16 (hydrogenated castor oil)< / cell><cell>0,5 % by weight< / cell>< / row><row><cell>Perfume< / cell><cell>0,3 % by weight< / cell>< / row><row><cell>Menthol Menthol< / cell><cell>0,3 % by weight< / cell>< / row><row><cell>Lactic acid< / cell><cell>0,1 % by weight< / cell>< / row><row><cell>Water< / cell><cell>ad 100% by weight< / cell>< / row><head xml:id="_d905260505">Example 7< / head><p xml:id="_d905260506" n="0116">A composition in the form of an emulsion comprising the following components:<title desc="title" / ><row><cell>Zinc stearate< / cell><cell>1,25 % by weight< / cell>< / row><row><cell>Magnesium sulfate< / cell><cell>0, 5 % by weight< / cell>< / row><row><cell>Sorbitan Isostearate & Polyglyceryl-3 Polyricinoleate< / cell><cell>4,5 % by weight< / cell>< / row><row><cell>Hexyldecanol & hexyldecyl laurate< / cell><cell>25,0 % by weight< / cell>< / row><row><cell>Glycerol< / cell><cell>2,0 % by weight< / cell>< / row><row><cell>Citric acid< / cell><cell>0,4 % by weight< / cell>< / row><row><cell>Calcium hypophosphite< / cell><cell>0,1 % by weight< / cell>< / row><row><cell>N,N-dimethylglycine hydrochloride< / cell><cell>0,4 % by weight< / cell>< / row><row><cell>Perfume< / cell><cell>0,2 % by weight< / cell>< / row><row><cell>Preservatives< / cell><cell>q. s.< / cell>< / row><row><cell>Water< / cell><cell>ad 100% by weight< / cell>< / row><head xml:id="_d905260547">Example 8< / head><p xml:id="_d905260548" n="0117">Compositions in the form of a kit containing the following forms of administration and components: Kit component 1: Shampoo containing the following components:<title desc="title">Kit component 1: Shampoo containing the following components:Sodium Myrethsulfate4,0 % by weightSodium laureth sulfate4,0 % by weightDisodium laurethsulfosuccinate3,0 % by weightTocopheryl acetate0,3 % by weightCitric acid1,0 % by weightNa-N, N-dimethylglycinate1,0 % by weightPerfume0,3 % by weightPotassium sorbate0,2 % by weightSodium benzoate0,1 % by weightWaterad 100% by weightKit component 2: Composition in the form of a capsule containing the following components:Kit component 2: Composition in the form of a capsule containing the following components:NutrientSingle dose [mg]% by weightVitamin C10029,5Vitamin E (α-tocopherol)102,9Niacin185,3Zinc51,5β-Carotene / provitamin A20,6Vitamin B61,80,5Vitamin B2 (riboflavin)10,3Vitamin B1 (thiamine)1,20,4Folic acid0,30,1Biotin0,120,0354Selenium Selenium0,030,0088Vitamin B120,0010,0003Calcium hypophosphite20058,9The capsule may also contain customary excipients, such as vegetable oil, and / or fillers.Example 9Compositions in the form of a kit containing the following forms of administration and components: Kit component 1: Shampoo containing the following components: Kit component 1: Shampoo containing the following components:Sodium Myrethsulfate4,0 % by weightSodium laureth sulfate4,0 % by weightDisodium laurethsulfosuccinate3,0 % by weightTocopheryl acetate0,3 % by weightCitric acid0,2 % by weightCalcium hypophosphite0,2 % by weightPerfume0,3 % by weightPotassium sorbate0,2 % by weightSodium benzoate0,1 % by weightWaterad 100% by weightKit component 2: Composition in the form of a capsule containing the following components:Kit component 2: Composition in the form of a capsule containing the following components:Vitamin C10033,2Vitamin E (α-tocopherol)103,3Niacin186,0Zinc51,7β-Carotene / provitamin A20,7Vitamin B61,80,6Vitamin B2 (riboflavin)10,3Vitamin B1 (thiamine)1,20,4Folic acid0,30,1Biotin0,120,0398Selenium Selenium0,030,0100Vitamin B120,0010,0003N,N-dimethylglycine hydrochloride16253,7The capsule may also contain customary excipients, such as vegetable oil, and / or fillers.Reference Example 1A composition in the form of a tablet (without Na dimethyl glycinate and calcium hypophoshite) containing the following components:Vitamin C8015,2Vitamin E (α-tocopherol)51,0Vitamin B210,2Vitamin B120,0020,0Zinc152,9Panthothenic acid101,9Biotin / vitamin H0,10,02Folic acid0,20,04Silicon Silicon101,9L-Cysteine51,0Millet extract30057,0L-Lysine10019,0The tablet may further contain conventional excipients such as sugar alcohol and / or fillers.Study Design and ResultsIn an in vitro investigation, the effect of calcium hypophoshite or Na dimethylglycinate and their combination in the cell culture model with human horn-forming keratinocyte cells was investigated. For this purpose, HaCaT cells were cultured for 1, 3, 5 and 7 days in DMEM medium (including 2.5% fetal calf serum and an antibiotic-antifungal mixture) and, inter alia, the viability and proliferation of the cells were determined by suitable measurement methods and the formation of the signal molecules relevant to cell growth was measured.It has been found that, in particular, the combination of calcium hypophoshite with Na-dimethylglycinate positively influences the growth relevant parameters of the HaCaT cells and the formation of growth factors (for example VEGF and intracellular calcium) has been significantly increased compared to the treatment of HaCaT cells with calcium hypophoshite or Na-dimethylglycinate alone.The composition according to the invention from Example 1 (verum composition with sodium dimethylglycinate and calcium hypophospite) and the composition from Reference Example 1 (placebo composition without sodium dimethylglycinate and calcium hypophospite) were taken for 6 months in a randomized, controlled and blinded application study on a test subject collective.The subjects were asked to subjectively evaluate the decrease in their hair loss after the administration was completed, these results being recorded with the aid of questions. Simultaneously, the hair density and the hair root activity were determined by established standard methods from the field of dermatology before and after ingestion (see, inter alia, Serrano-Falco C, Fernandez-Pugnaire MA, Serrano-Ortega S. Hair and scalp evaluation: the trichogram).During or after oral ingestion of the composition of the invention of Example 1, more subjects and subjects indicated that fewer hairs had failed compared to the control group with oral ingestion of the placebo composition. In the course of the objective measurements, it was found that, when the composition according to the invention from Example 1 was taken orally, an increase in the hair density and positive effects on hair root activity were detected in comparison with the control group.References included in the specificationThis list of documents cited by the applicant has been produced in an automated manner and is only included for the better information of the reader. The list is not part of the German patent application or utility model application. The DPMA does not take any adhesion for any faults or omissions.Cited Non-Patent LiteratureGuo E. L., Kata R. Diet and hair loss: effects of nutrient deficiency and supplement use. Dermatol Pract Concept. 2017; 7(1):1

[0005] Almohanna, Hind M et al., "The Role of Vitamins and Minerals in Hair Loss: A Review." Dermatology and therapy vol. 9.1 (2019): 51-70

[0007] Goldberg, L.J., Lenzy Y. Nutrition and hair. Clin Dermatol. 2010 Jul-Aug; 28(4):412-9

[0009] Jain, Pushpendra & Joshi, Himanshu & Das, Debajyoti. (2012). Drug that Coffees Hair Loss and Promotes Hair Growth-A Review. International Journal of Research in Pharmaceutical and Biomedical Sciences. 3. 1476-82

[0010] Almohanna et al.; Guo and Kata

[0013] Serono-Falcon C, Farandez-Pugnaire MA, Serono-Ortega S. Hair and scale evaluation: the trichogram [0101, 0126]

Claims

A composition comprising (a) phosphonic acid and / or at least one salt of phosphinic acid, and (b) dimethyl glycine and / or a salt of dimethyl glycine.Composition according to any one of the preceding claims, in which the salt of phosphinic acid (A) is bivalent.Composition according to any one of the preceding claims, in which the salt of phosphinic acid (A) is the calcium salt, i.e. calcium hypophosphite.Composition according to any one of the preceding claims, wherein the composition contains 0.0001 to 35.0 weight percent (wt.%), preferably 0.001 to 25.0 wt.%, more preferably 0.01 to 15.0 wt.%, even more preferably 0.1 to 10.0 wt.%, and particularly preferably 0.1 to 5.0 wt.% phosphinic acid and / or a salt of phosphinic acid, in particular calcium hypophosphite.Composition according to any of the preceding claims, wherein the composition contains 0.0001 to 35.0 weight percent (wt%), preferably 0.001 to 25.0 wt%, more preferably 0.01 to 15.0 wt%, even more preferably 0.1 to 10.0 wt%, and particularly preferably 0.1 to 5.0 wt% dimethyl glycine and / or a salt of dimethyl glycine.Composition according to any of the preceding claims, wherein the composition comprises dimethyl glycine and / or a salt thereof as well as phosphonic acid and / or a salt thereof in a molar ratio of 1:10 to 10:1, preferably 1:5 to 5:1 and particularly preferably 1:2 to 2:1.Composition according to any one of the preceding claims, wherein the composition further comprises at least one further active ingredient c) selected from amla extract, β-carotene, biotin, carnitine, curcumin, echinacea, ectoin, iron, folic acid, pomegranate extract, green tea extract, millet extract, millet oil, pumpkin kernel oil, creatine, L-cysteine, L-lysine, niacin, niacinamide, pantolactone, panthenol acid, piperine, procyanidin, rosemary extract, saw palm extract, horsetail extract, selenium, silicon, taurine, tocopheryl acetate, tomato extract, ubiquinone-10, Vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin E, zinc, and combinations thereof.The composition of any preceding claim, wherein the composition is configured for oral use.Use of the composition according to any of the preceding claims as a food supplement, in particular for promoting the metabolism of the hair and / or of the skin and / or for promoting hair growth and / or for treating and / or preventing hair loss.Use of the composition according to any of the preceding claims for improving the condition of the hair and / or skin and / or for promoting metabolism of the hair and / or skin and / or for promoting hair growth and / or for treating and / or preventing hair loss.Use according to claim 10, wherein the hair loss is selected from Alopecia areata (circular hair loss), Alopecia androgenetica (hereditary hair loss) in women and men, diffuse alopecia (diffuse hair loss), age-related hair loss (senescent alopecia) and chemotherapy-related hair loss.Use according to claim 10 or 11, wherein the use is a medical or cosmetic use.Kit comprising a) dimethyl glycine and / or a salt of dimethyl glycine, in particular dimethyl glycine, b) phosphonic acid and / or at least one salt of phosphinic acid, in particular calcium hypophosphite, wherein a) and b) are present in separate administration forms.