Composition comprising avenanthramide with improved skin penetration

Abstract

To provide a composition, or a customary preparation or formulation, comprising an avenanthramide, which exhibits enhanced skin penetration to achieve high bioavailability for the avenanthramide or an analogue avenanthramide compound.SOLUTION: The present invention provides a composition comprising: at least one avenanthramide selected from the group of avenanthramides A, B, C, D, E, F, G, H, L and mixtures of these avenanthramides; and at least one penetration enhancer, which is a straight-chain alkanediol having 3 to 12 carbon atoms.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention generally relates to certain avenanthramides and at least one amide having improved skin permeability. a composition comprising or consisting of at least one penetration enhancer; the use of such compositions as cosmetics or medicines; and methods of preparing compositions comprising said compositions. This applies to cosmetics or pharmaceuticals. [Background technology]

[0002] Avenanthramides (hereafter referred to as Avns or a single avenanthramide compound) Avn is a compound that is a mixture of anthranilic acid and hydroxycinnamic acid with an amide bond. It is a low molecular weight phenolic amide containing an acid moiety, and is found in both A. sativa and A. nud a is also a group of naturally occurring phenolic amides in oats. First identified as a phytoalexin produced by plants in response to exposure to pathogens Oats contain a unique group of approximately 40 different types of Avns, which It is present in both grains and leaves. The most abundant is Avn A(N-(4'- hydroxycinnamoyl)-5-hydroxyanthranilic acid), Avn B (N-(4' -Hydroxy-3'-methoxycinnamoyl)-5-hydroxyanthranilic acid) and Avn C (N-(3'-4'-dihydroxycinnamoyl)-5-hydroxyanthracene 5-hydroxyanthranilic acid), which are amides of 5-hydroxyanthranilic acid and p-coumarin These Avns have the structures: They are expressed genetically in the seeds and occur in almost all crushed fractions, but their highest concentrations are It occurs in the outer layer of the bran and kernel [Boz H, Czech Journal of f Food Sciences, 2015, Vol. 33(No. 5): pp. 399-404] The total content of avenanthramides (Avns) in oat grain varied with cultivar and agronomic treatment. The range was found to be approximately 2-700 mg / kg (0.0002-0.07%) depending on the Maliarova M et al., Journal of the Brazilian Ch. emical Society, 2015, Vol. 26(No. 11), pp. 2369-2378. [Ji]

[0003] The extraction of Avns from oats can be performed using various solvent compositions, e.g., pure or diluted Ethanol and methanol were used. Extraction procedures have been achieved using, for example, naked oats, 50% aqueous ethanol, etc., under high heat. [Tong L et al., Journal of Integrative Agriculture Culture, 2014, Volume 13, Page 1809].

[0004] Maliarova, M. et al., Journal of the Brazilian Chemical Society, 2015, Vol. 26(11), 2369-2378 Page, Methanol, Ethanol, and the Extraction of Avns from Naked Oat Bran The efficiency of isopropanol and ethanol was compared. The optimum conditions for the highest yield of Avns were The extraction temperature was 55°C and the extraction time was 165 min.

[0005] Avenanthramide has excellent antioxidant activity both in vitro and in vivo. and diseases associated with cellular oxidative dysfunction and oxidative stress, such as neurodegeneration and and anti-inflammatory, anti-irritant, anti-atherogenic and anti-inflammatory properties that may prevent or limit the development of cardiovascular disease. and antiproliferative activity, providing additional protection against skin irritation, aging, CHD and cancer Several studies have demonstrated that avenanthramides are useful in cosmetics and and / or in the field of therapeutic agents [Perrelli A et al., Oxidati ve Medicine and Cellular Longevity, 2018, DOI:10.1155 / 2018 / 6015351].

[0006] The antioxidant activity of Avns was similar to that of typical cereal constituents ferulic acid, gentisic acid, and p-hydroxybutyric acid. Protocatechuic acid, silyloxybenzoic acid The antioxidant activity of these compounds was found to be 10 to 30 times higher than that of vanillin, vanillic acid, and valinic acid. Avns differ in antioxidant activity, with Avn C having the highest activity, followed by Avn B and A. This is followed by vn A. Oat extracts rich in Avns showed LD Oat antioxidants lower serum cholesterol and inhibit LDL oxidation. Inhibits terol oxidation and peroxidation, potentially reducing cardiovascular risk This has been confirmed in animal studies and in human clinical trials. Consumption of these foods, not only due to their high fiber content, but also due to Avns, is associated with increased risk of colon cancer. Another study showed that Avns-rich oat extracts can reduce The compound has been shown to inhibit atherosclerosis and activation of the NF-kB transcription factor. NF-kB transcription factors are regulators of infection and inflammation [Hueseyin B oz, Phenolic Amides (Avenanthramides) in Oa ts-A Review, Czech J.Food Sci., Vol. 33, 2015(5 No., pp. 399-404.

[0007] Additionally, avenanthramides have been shown to be useful in the treatment and prevention of itch or hearing loss, or They are known to be beneficial as 5-lipoxygenase inhibitors.

[0008] Avenanthramide analogues: dihydroavenanthramide Hydroxyphenylpropamide D (CAS 697235-49-7, INCI name: Hydroxyphenylpropamide Benzoic acid; the active ingredient in SymCalmin® provided by Symrise ) inhibits mast cell degranulation and exerts anti-inflammatory effects via interaction with the neurokinin-1 receptor It is known to show utility.

[0009] These potent, beneficial biological activities make avenanthramides suitable for use in humans and animals. For oral and / or topical application to the skin, for nutritional, cosmetic and health uses. These have made them valuable and extremely interesting natural active ingredients for

[0010] On the other hand, in skin and scalp protection and skin care and scalp care and / or for use in the prevention and / or treatment of skin diseases, For the development of new substances or compositions with improved skin permeability of the composition, There is a continuing need in the medical and pharmaceutical industries.

[0011] The biological effects of the skin usually require the penetration of active compounds through the skin.

[0012] As the main permeability barrier of the skin, the stratum corneum (SC) is composed of keratinocytes embedded in extracellular lipids. It consists of cells.

[0013] To reach therapeutic drug concentrations, the drug must penetrate the stratum corneum. Due to its biochemical composition, the stratum corneum is selectively permeable. and moderately lipophilic molecules (having a molecular weight of less than 500 Da and a log P of 1-4) It is likely that these physicochemical properties are not present in the macromolecular bases that are capable of penetrating the skin. Other drugs based on glycerol are primarily hindered by the low permeability of the skin and usually lack the appropriate Penetration enhancement strategies are needed.

[0014] Skin penetration and permeation is a complex process with various barriers to crossing. First, the cosmetically or pharmaceutical active substance is dissolved in a conventional preparation or formulation. Then, the granules must be allowed to diffuse from the inside of the formulation to the SC interface. The active agent passively diffuses through the formulation and the barrier into the barely permeable SC. It is known that as gP increases, permeability increases. Diffusion through the stratum corneum is favored by most hydrophilic and amphiphilic substances, although more lipophilic substances are favored. The deeper skin layers have a higher hydrophilicity, so the active An optimal hydrophilic-lipophilic balance is essential for percutaneous penetration of

[0015] Many substances have been investigated and used for their penetration enhancing activity. The mode of action is specified as a skin penetration enhancer.

[0016] Heuschkel S et al., European Journal of Pharma Ceutics and Biopharmaceutics, Volume 72, 2009, 55 Pages 2-560 describe the use of model drug dihydrochloride in microemulsions as penetration enhancers. 1,2- for avenanthramide D (dihydroavenenthramide) The effect of the alkanediol vehicle is described.

[0017] On the one hand, the complexity of skin penetration and permeation mechanisms, and on the other hand, the chemical and The effect of skin penetration enhancers on transdermal delivery may vary depending on their physicochemical properties or type of formulation. Moreover, the use of one penetration enhancer in combination with one active substance does not allow for accurate prediction. The action of cannot simply be generalized to apply to another, different active substance.

[0018] The above-mentioned avenanthramides or preparations containing avenanthramides are hydrophilic substances, Therefore, it shows poor permeability through the SC. It is extremely difficult to achieve therapeutic concentrations or local bioavailability of ramido substances. It is difficult. Summary of the Invention [Problem to be solved by the invention]

[0019] Therefore, the active substance, i.e. avenanthramide or an analog avenanthramide compound Avenan exhibits enhanced skin penetration to achieve high bioavailability of the product It is an object of the present invention to provide a composition or conventional preparation or formulation comprising sulamide. be.

[0020] In particular, the goal of the present invention is to enhance the penetration of one or more avenanthramides into the skin. and the beneficial biological activity of the avenanthramides, compositions or conventional formulations. one or more biodegradable cosmetic or medicinal substances that do not interfere with the properties of the composition itself Compositions containing well-established, safe, easy-to-use and stable penetration enhancers The idea is to propose something. [Means for solving the problem]

[0021] Surprisingly, the penetration of avenanthramide through the skin was improved by the addition of a penetration enhancer. It has been shown that this can be significantly enhanced. The above object is achieved according to a first aspect of the present invention, (i) avenanthramides A, B, C, D, E, F, G, H and L and their avenanthramides At least one avenanthramide selected from the group consisting of a mixture of avenanthramides, And (ii) at least one penetration enhancer This is achieved by providing a composition comprising or consisting of:

[0022] In a second aspect, the present invention relates to a cosmetic product, in particular a skin protection and skin care product, a scalp care product, For skin care, scalp care, hair care, nail care, or if you have a skin condition or intolerance For sensitive skin, skin irritation, skin redness, wheals, pruritus (itching), skin aging, wrinkle formation, skin Loss of skin volume, loss of skin elasticity, pigmentation spots, pigmentation abnormalities, or dry skin, i.e. skin maintenance. The present invention relates to the use of said composition in the prevention and / or treatment of dry skin requiring moisture.

[0023] In a third aspect, the present invention relates to a method for treating a skin or keratinopathy, particularly a barrier-related disease, comprising: Contains inflammatory, immunoallergic, atherogenic, dry or hyperproliferative components Prevention and / or treatment of skin diseases associated with increased ROS generation, or prevention and / or treatment of skin diseases associated with increased ROS generation The use of said composition as a medicament for use in the prevention and / or treatment of .

[0024] In a fourth aspect, the present invention relates to a method for preparing a cosmetic or pharmaceutical preparation / formulation comprising the steps of: Concerning the use of compositions.

[0025] Finally, the present invention relates to a process for preparing the composition according to the invention.

[0026] The invention is more particularly defined in the appended claims. This, as well as preferred modifications thereof, further objects and advantages, are also to be understood in connection with the accompanying examples. This will become apparent from the detailed description below. [Brief description of the drawings]

[0027] [Figure 1] FIG. 1 is a graph showing the permeation behavior of Avn A, Avn B, and Avn L compared to dihydroavenanthramide D (DhAvn D) in the absence of a permeation enhancer. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] The first main component of the composition according to the first aspect of the present invention comprises at least one active ingredient, It is an avenanthramide of the species. An active agent is an ingredient in a composition or preparation that is biologically active.

[0029] The phrase "at least one" when used in this document means, for example, may contain any one or more avenanthramides. Further, the phrase "at least one" when applied to a list , means any one combination of the items specified in the list.

[0030] In the context of this invention, the common term "avenanthramide" (anthranilic acid amide) is used. The term refers, inter alia, to members of the group of phenolic alkaloids, i.e., mainly those from oat (A vena sativa), which is described in detail hereinafter. The eggs of the cabbage white butterfly (Pieris brassicae and P. rapa e) and fungal-infected carnation (Dianthus caryophyllus) s), or as described in more detail hereinafter. The present invention relates to non-naturally produced avenanthramide analogues, such as those described in It is believed to taste

[0031] The avenanthramides of the compositions of the present invention are found in nature and are isolated and purified from oats. The two main species of oat are Avena sativa L. and Avena nuda L. (synonyms according to Gillet and Magne Avena sativa subsp. nuda (L.) and Avena by Korn Na sativa var. nuda (L.) is one example. Avenanthramide is The highest concentrations appear to be in the canopy regions, husks, trichomes or straw. A number of distinct avenanthramides have been isolated from oat kernels [Collin s, Journal of Agricultural and Food Chemistry stry, vol. 37 (1989), pp. 60-66].

[0032] Avns can be represented by the following general formula 1: [ka]

[0033] Table 1 below shows examples of naturally occurring Avns based on general formula 1.

[0034] [Table 1]

[0035] Several studies have demonstrated that these avenanthramides have anti-inflammatory, antioxidant, anti-itch, and anti-irritant properties. and anti-atherogenic activity.

[0036] A naturally occurring single avenanthramide or an avenanthramide as described above The mixture is produced by extraction from the Avena genus of plants, particularly from any oat species, even fresh oats. Or dried or parts thereof, e.g. oats Avena sativa or A. Crushed kernels, uncrushed kernels, husks, trichomes or endothelial cells of the vena nuda species It is obtained from barley straw and isolated and / or fractionated.

[0037] The extraction solvent (extraction solvent) for advantageously extracting the avenanthramide compounds used according to the present invention is The solvent is selected from the group consisting of a mixture of water and an organic solvent, the organic solvent being preferably a food grade solvent. or a solvent suitable for cosmetic or pharmaceutical preparations. Needless to say, such solvents , food, cosmetic or pharmaceutical preparations and must be compatible with them. stomach.

[0038] In a more preferred variant, the extraction solvent comprises a mixture of water and alcohol or acetone. The alcohol is preferably methanol, ethanol, n-propanol, isopropanol. , n-butanol, isobutanol, t-butanol and mixtures thereof, i.e. The most preferred extraction solvents for the extraction step of the present invention are selected from the group consisting of The extractant is methanol, ethanol, n-propanol, isopropanol or acetone. tonnes, or any mixture of said solvents, each in admixture with water. The use of pure organic solvents is not favored by the simultaneous extraction of triglycerides.

[0039] The ratio of water to organic solvent in the extraction solvent, preferably the ratio of water to alcohol, The mixture ratio of acetone to water or the mixture ratio of acetone to water was determined based on the extraction solvent produced. , in the range of 10:90 to 90:10 (v / v), preferably 20:80 to 80:20 (v / v), and most preferably in the range of 30:70 to 70:30 (v / v). do.

[0040] Particularly preferred extraction solvents (extractants) are methanol / water (3:7), methanol / water (1 :1), methanol / water (7:3), ethanol / water (3:7), ethanol / water (1: 1), ethanol / water (1:4), ethanol / water (7:3), isopropanol / water ( 3:7), isopropanol / water (1:1), isopropanol / water (7:3), acetonitrile The mixtures used were acetone / water (3:7), acetone / water (1:1), and acetone / water (7:3).

[0041] To improve the extraction yield, the oat source is heated at 30 to 80°C, preferably 40 to 70°C. The extract is made from crushed oat kernels at a temperature in the range of 50-60°C. The extraction yield increases with increasing temperature between 40 and 70°C.

[0042] Apart from avenanthramide compounds isolated and purified from natural sources, naturally occurring The pure avenanthramides can be produced by organic synthesis. Methods of knowledge synthesis are described, for example, in U.S. Pat. No. 6,096,770 and U.S. Pat. 7,392, Japanese Patent No. J60019754A and Hungarian Patent No. HU2009 An example is given in No. 96B.

[0043] The synthetic avenanthramide substances prepared above were extracted and isolated from oats, and the corresponding It is identical to the naturally occurring avenanthramide compound found in

[0044] According to the present invention, the definition of an avenanthramide compound is an analog compound represented by the following formula 3: Dihydroavenanthramide D (DhAvn D) (2-(3-(4-hydroxyphenyl -)propanoyl-)amidobenzoic acid) is not included. [ka]

[0045] Therefore, dihydroavenanthramide D (DhAvn D) is the same as the above definition of avenanthramide. Excluded from righteousness.

[0046] The analog avenanthramide compound dihydroavenanthramide D(2-(3 -(4-hydroxyphenyl-)propanoyl-)amidobenzoic acid) is less preferred. stomach.

[0047] In addition to the naturally occurring avenanthramides listed above, N-(4'-hydroxycinnamoyl)- 3-Hydroxyanthranilic acid (YAvn I) and N-(3'-4'-dihydroxy The recombinant enzymes, including 3-hydroxyanthranilic acid (YAvn II), Novel avenanthramide analogues were formed in the mother, which were synthesized from phenolic esters. Two plant genes (4 from tobacco) encoding the major proteins involved in the synthesis Saccharomyces cerevisiae (cl-2 and artichoke-derived hct) was used It was generated by engineering a S. cerevisiae strain. In addition, YAvn I and YAvn II share structural similarities with Avn A and Avn C. Share each one.

[0048] Generally, consumers recognize the difference between naturally prepared compounds and synthetically prepared compounds. In the context of the present invention, naturally occurring avenanthramides obtained from natural sources or synthetically produced Naturally occurring avenanthramides that have been synthesized are preferred and may be used in the same manner. Developmental avenanthramides may also be important.

[0049] The term "avenanthramide" refers to the various isomers that exist, especially those that occur naturally. Intact trans-isomer as well as cis-isomer, e.g. photoisomerization induced by exposure to light cis-isomerized double bonds (formula 1 or 2 with n=1) or 1 or 2 Avenanthramides with two cis-isomeric double bonds (formula 1 or 2 with n=2) It is intended to include, among others.

[0050] In particular, within the context of the present invention, avenanthramides are represented by the general formula 1 and defined in Table 1. or any one of the avenanthramide compounds as described above. Any isomer.

[0051] In a preferred variant of the invention according to the first aspect, the composition comprises avenanthramides A, B, At least one selected from the group consisting of C, G, H, K, L, R, and mixtures thereof In another variation of the present invention, the avenanthramides include A, B, C, L and mixtures thereof. More preferred is a composition comprising at least one avenanthramide selected from the group consisting of It is preferable that at least one a selected from the group consisting of A, B, L and mixtures thereof. Compositions containing venanthramide are most preferred.

[0052] Particularly preferred are compositions containing avenanthramide A or avenanthramide B. A composition containing avenanthramide C, or a composition containing avenanthramide G. Composition, or composition containing avenanthramide H, or composition containing avenanthramide K or a composition containing avenanthramide L, or a composition containing avenanthramide R. do.

[0053] In another variation, the composition of the present invention comprises avenanthramides A, B, C, G, H, K, L ( Non-Collins abbreviation; CAS number 172549-38-1) (also called O or 2pd) and R, A combination or mixture of avenanthramides is thus Here are 1 minutes of the list of other designs for the squirrel: A / B;A / C;A / G;A / H;A / K;A / L;A / R; B / C;B / G;B / H;B / K;B / L;B / R; C / G;C / H;C / K;C / L;C / R; G / H;G / K;G / L;G / R; H / K;H / L;H / R; K / L;K / R;および L / R; A / B / C;A / B / G;A / B / H;A / B / K;A / B / L;A / B / R;A / C / G;A / C / H;A / C / K;A / C / L;A / C / R;A / G / H;A / G / K;A / G / L;A / G / R;A / H / K;A / H / L;A / H / R;A / K / L;A / K / R; A / L / R;B / C / G;B / C / H;B / C / K;B / C / L;B / C / R;C / G / H;C / G / K、C / G / L;C / G / R;G / H / K;G / H / L;G / H / R;H / K / L;H / K / R;K / L / R;A / B / C / G;A / B / C / H;A / B / C / K; A / B / C / L;A / B / C / R;A / C / G / H;A / C / G / K;A / C / G / L; A / C / G / R;A / G / H / K;A / G / H / L;A / G / H / R;A / H / K / L; A / H / K / R;A / K / L / R;B / C / G / H;B / C / G / K;B / C / G / L; B / C / G / R;C / G / H / K;C / G / H / L;C / G / H / R;G / H / K / L; G / H / K / R and H / K / L / R.

[0054] Note that the numbers of the slightly larger brackets are A / B, A / C, A / L, B / C, B / L, A / B / C, A / B / L, A / C / L, A / C / L,

[0055] In addition to the above avenanthramide compounds or combinations of avenanthramides, the composition further comprises Venanthramides A, B, C, G, H, K, L (non-Collins abbreviations; CAS number 172549 -38-1) (also called O or 2pd) and one or more avenans other than R avenanthramides, e.g. avenanthramides D, E, FU, X, Y (also called 2), AA, CC or OO or any of the remaining avenanthramide compounds identified in Table 1 It can be included in the following:

[0056] At least one avenanthramide is isolated and synthesized from a natural source, e.g., oat. and / or as a fractionated single avenanthramide compound, or as described above. The single avenanthramides A, B, C, G, H, and K were obtained by organic synthesis as described above. , L or R compound, or two of the above single avenanthramide compounds. The above mixture is added to the composition according to the first aspect of the present invention.

[0057] Alternatively, the at least one avenanthramide may be Oat extract fractions containing A, B, C, G, H, K, L or R compounds or mixtures thereof to the composition according to the first aspect of the invention in the form

[0058] As a further alternative, the at least one avenanthramide may be a single avenanthramide as described above. The avenanthramide compound includes at least one avenanthramide A, B, C, G, In combination with oat extract fractions containing H, K, L or R compounds or mixtures thereof It is added to the composition.

[0059] The concentration of avenanthramide in the composition, i.e., the concentration of the active substance or active ingredient, is The amount of the active ingredient or active substance to be treated may vary widely and may vary depending on the disease or condition being treated and the nature of the active ingredient or active substance. quality and activity, the desired action, and whether the active substance or active ingredient reaches its intended target The outcome will depend on a variety of factors, including the ability and speed to

[0060] At least one avenanthramide or an avenanthramide as described above The mixture is present in the composition at a concentration of 0.0001 to 5.0% by weight based on the total weight of the composition. In a preferred variant, the composition comprises at least one avenant. 0.0005-2% by weight of the total composition. 0.0% by weight or total amount, and even more preferably 0.001 to 1.0% by weight. Contains by degree or total amount.

[0061] The avenanthramides identified above are hydrophilic substances and therefore weakly permeable through the SC. Avn A, Avn B, and Avn L indicate permeability. <Avn B<Av n L, and has weaker permeation behavior than dehydroavenanthramide D (DhAvn D). However, Avn C was better absorbed than dehydroavenanthramide D (DhAvn D). To see through.

[0062] The second major component of the composition according to the first aspect of the invention is at least one penetration enhancer. "Penetration enhancer" refers to an agent that enhances the penetration of one or more active substances or ingredients in a composition through the skin. to the skin (dermal delivery) or through the skin to other tissues (transdermal delivery) and through the body Alter (usually increase or accelerate) the rate of transduction of the substance in the intended target. The substance used to achieve therapeutic concentrations or local bioavailability of It means.

[0063] In the context of the present invention, the term "at least one" refers to only one penetration enhancer or or more than one penetration enhancer, i.e., two, three or even more It is intended to include different penetration enhancers.

[0064] "Dermal active delivery" refers to the delivery of an active ingredient or substance to the skin (epidermis and / or dermis). ) and deliver their efficacy and benefits thereto. or refers to the administration of an active agent to the surface of an individual's skin.

[0065] "Transdermal drug delivery" or "transdermal drug administration" refers to the process by which a drug passes through the skin tissue. "Transdermal" refers to administering a drug to the surface of an individual's skin so that the drug enters the individual's bloodstream. The term refers to "transmucosal" drug administration, i.e., the drug passes through mucosal tissue and enters the bloodstream of an individual. The drug is administered to a mucosal (e.g., sublingual, buccal, vaginal or rectal) surface of an individual so as to enter the bloodstream. It is intended to include administering to

[0066] "Localized drug delivery" or "localized drug administration" is used to treat, for example, various skin disorders. This means delivering a topical drug of a pharmacologically active agent to the skin or mucosa, as in the case of the treatment of As used herein, these terms have their conventional meanings, as opposed to transdermal administration. Topical drug administration often produces a local rather than a systemic effect. Used for.

[0067] Transdermal drug delivery avoids first-pass metabolism and provides long-lasting drug release Localized drug delivery can be used to deliver a drug to the surface to be treated. This allows for direct application to the skin, which helps localize treatment and minimize side effects. However, the skin, which has evolved to block the influx of toxins into the body, The stratum corneum is responsible for this barrier, and is therefore very permeable to the passage of foreign molecules. The stratum corneum contains keratinocytes embedded in the upper layer (15 μm) of the skin. possess a unique hierarchical structure of lipid-rich matrix (Bouwstra, 1997) Overcoming this barrier safely and reversibly has great potential for transdermal or topical delivery. This remains a fundamental problem in the field of

[0068] One well-known approach is to modify the lipid profile in the stratum corneum or to induce the release of active agents within the stratum corneum. By increasing the solubility of the active ingredient or substance through the stratum corneum, By using substances or chemicals that can enhance or accelerate the passage of sexual components. be.

[0069] The ability of a substance to accelerate stratum corneum permeation through the skin barrier depends on the physicochemical properties of the active substance. The desired dermal delivery depends on the molecular properties (e.g., melting point, molecular weight, molecular shape, charge, lipophilicity, etc.). Optimal selection of penetration enhancers and / or complete compositions or formulations to achieve Research may need to be conducted on new active substances to determine this.

[0070] Sulfoxides (e.g., dimethyl sulfoxide, DMSO), azones (e.g., lauroyl Capram), pyrrolidones (e.g., 2-pyrrolidone, 2P), alcohols and alkanoates Many substances, including alcohol (ethanol, or decanol), surfactants, and terpenes, are Although they have been studied for their penetration enhancing activity, only a few have actually been used in practice A number of promising sites and modes of action have been identified for skin penetration enhancers.

[0071] Even if an entire library of chemical penetration enhancers exists, on the one hand, skin permeability and On the one hand, the complexity of the mechanisms of penetration of the active substances into the skin and on the other hand, the chemical and physicochemical properties of the active substances It is possible to make valid predictions about the effect of penetration enhancers on dermal or transdermal delivery. and the action of one penetration enhancer compound in combination with one active agent is not merely It cannot be generalized to apply to different active substances.

[0072] Surprisingly, diols, polyols, alcohols, dimethyl isosorbide (INCI name ), triethyl citrate, butylene carbonate, glycerin carbonate, dipropylene and a penetration enhancer selected from the group consisting of ethylene glycol, propylene glycol, or any mixture thereof. The combination significantly improved the skin permeability and penetration of avenanthramide. This effect is demonstrated by the following examples. Thus, by increasing the penetration and permeability of the skin, the active substance, i.e. Thus, the bioavailability of the avenanthramides may be increased in the intended target.

[0073] A diol is a chemical compound containing two hydroxyl groups. In a preferred variant, The diol is a linear 1,2-alkanediol having 3 to 12 C atoms, preferably ,2-Propanediol (propylene glycol), 1,2-butanediol, 1,2- Pentanediol (Hydrolite-5), 1,2-Hexanediol (Hydro lite-6), 1,2-heptanediol, 1,2-octanediol, 1,2-nonaphthalene 1,2-Decanediol or 1,2-Dodecanediol; 1,3-Butane Diol (butylene glycol), 1,3-propanediol, 1,4-butanediol , 1,1'-oxydi-2-propanol (dipropylene glycol) and its isomers and any mixture thereof.

[0074] A polyol is an organic compound containing multiple hydroxyl groups. In a preferred variant , Polyols are 1,2,3-propanetriol (glycerin), sorbitol, fluorine The sugar is selected from the group consisting of lactose, maltose, and trehalose.

[0075] In a preferred variant of the composition according to the invention, the penetration enhancer is a diol, preferably a 3- Linear 1,2-alkanediols with 12 C atoms, especially 1,2-propanediol (Propylene glycol), 1,2-butanediol, 1,2-pentanediol (Hy Hydrolite-5), 1,2-Hexanediol (Hydrolite-6), 1,2 -Heptanediol, 1,2-Octanediol, 1,2-Nonanediol, 1,2-De 1,2-dodecanediol, 1,3-butanediol (butylene glycol) Recall), 1,3-propanediol, 1,4-butanediol, 1,1'-oxydi -2-propanol (dipropylene glycol) and its isomers; polyols, preferably Sorbitol, fructose, maltose, trehalose; alcohol; dimethyl isopropyl Sosorbide (INCI name); Triethyl citrate; Butylene carbonate; Glycerin dipropylene glycol or any mixture thereof. It is selected.

[0076] Among the above-mentioned penetration enhancers, linear 1,2-alkanediols having 3 to 12 C atoms Among 1,2-alkanediols, 1,2-pentanediol is preferred. 1,2-hexanediol and 1,2-octanediol are demonstrated in the examples below. As mentioned above, 1,2-hexanediol is the most preferred single It is a diol.

[0077] Even though the blend of penetration enhancers was used at a lower concentration, the following examples show that As demonstrated by the mixture of 1,2-hexanediol and 1,2-octanediol, The combination is even more efficient than this.

[0078] Furthermore, as demonstrated in the examples below, 1,2-hexanediol and 1, A blend of 2-hexanediol and 1,2-octanediol showed a 1, It performed better than 2-pentanediol.

[0079] According to the present invention, the penetration enhancer does not include glycerin. Excluded from the definition of penetration enhancers.

[0080] The penetration enhancer glycerin is less preferred.

[0081] In a preferred variant, the composition according to the invention does not contain glycerin as a penetration enhancer. .

[0082] 1,2-alkanediols are known to possess skin moisturizing properties and therefore may be useful in treating itching. This is because the skin that is affected is often dry, sensitive, or damaged. The use of 1,2-alkanediol penetration enhancers such as Providing additional benefits in skin care and scalp care preparations.

[0083] A combination of the penetration enhancers 1,2-hexanediol and 1,2-octanediol was also used to Enhances the performance of preservatives in formulations, allowing compositions to have lower preservative levels This can help with itchy skin with dry, sensitive or damaged skin. This is particularly useful for

[0084] The amount of penetration enhancer present in the composition according to the present invention is from 0.01 to 0.01% by weight based on the total weight of the composition. It can be between 1 and 10.0% by weight. In a preferred variant, the composition contains a penetration enhancer. The concentration of the agent is 0.5 to 7.0% by weight based on the total weight of the composition, and more preferably More preferably, it may be between 0.1 and 5.0% by weight based on the total weight of the composition. .

[0085] In a preferred variant of the composition according to the invention, the penetration enhancer is adapted to these different penetration activities. Accordingly, the following concentration ranges: C5 as defined above, each based on the total weight of the composition diol at a concentration of 0.5-6 wt.%, or C6 diol as defined above at 0. 2-3% by weight, or 0.1-2% by weight of a C7 diol as defined above. or a C8 diol as defined above at a concentration of 0.1 to 1% by weight, or The C10 diol as defined above is used in a concentration of 0.01 to 0.5% by weight.

[0086] As demonstrated in the examples below, the addition of one of the above penetration enhancers enhances the efficacy of Avena. The permeability of the sucralamide A, B, C, G, H, K, L, or R is significantly increased. In addition, the addition of one of the above penetration enhancers may enhance the effect of avenanthramide A, B, C or More preferably, the permeability of one of the above permeation enhancers is significantly improved. Addition of seeds significantly improved the permeability of one of the avenanthramides A, B or L. The modulation of permeability to avenanthramide A was dependent on the concentration of the penetration enhancer. In some cases, the range is 15% to 170%, preferably 15% to 65%, and avenanthramide B The preferred range is 35% to 95% for avenanthramide L. is in the range of 115% to 170%.

[0087] In the compositions according to the invention, various cosmetic or pharmaceutical active substances, i.e. The differential distribution of the various avenanthramides in the stratum corneum of skin exposed to the composition In the layers, each composition requires a different composition of penetration enhancer.

[0088] A preferred variant of the composition according to the invention comprises two or even more penetration enhancers. Combinations of two or more penetration enhancers may be used. Thus, the permeability of different cosmetic or pharmaceutical active substances in the composition can be selectively controlled. The composition contains two different avenanthramides having different structures. In the case of a composition comprising one or more of the following, two different penetration enhancers may be combined in the composition: One has an improved effect against the first avenanthramide, and the other has an improved effect against the second avenanthramide. Each enhancer has improved activity against the mide and is required to achieve the desired enhancement. The concentration of the promoter may be less than that required when any of the promoters are used individually. do.

[0089] In a preferred variant, the composition according to the first aspect of the invention comprises one of the following combinations: Contains one of: Avn A and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-Butanediol, 1,1'-oxydi-2-propanol (dipropylene glycol in combination with one or more of the following: Avn B and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-Butanediol, 1,1'-oxydi-2-propanol (dipropylene glycol in combination with one or more of the following: Avn C with 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-Butanediol, 1,1'-oxydi-2-propanol (dipropylene glycol in combination with one or more of the following: Avn G, 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-Butanediol, 1,1'-oxydi-2-propanol (dipropylene glycol in combination with one or more of the following: Avn H and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-Butanediol, 1,1'-oxydi-2-propanol (dipropylene glycol in combination with one or more of the following: Avn K and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-Butanediol, 1,1'-oxydi-2-propanol (dipropylene glycol in combination with one or more of the following: Avn L, 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-Butanediol, 1,1'-oxydi-2-propanol (dipropylene glycol or glycerin; or Avn R and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-Butanediol, 1,1'-oxydi-2-propanol (dipropylene glycol or glycerin.

[0090] In a more preferred variant, the composition according to the first aspect of the invention comprises one or more of the following combinations: Contains one of: Avn A and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-butanediol, or 1,1'-oxydi-2-propanol (dipropylene glycols); Avn B and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-butanediol, or 1,1'-oxydi-2-propanol (dipropylene glycols); Avn C with 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-butanediol, or 1,1'-oxydi-2-propanol (dipropylene glycols); Avn G, 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-butanediol, or 1,1'-oxydi-2-propanol (dipropylene glycols); Avn H and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-butanediol, or 1,1'-oxydi-2-propanol (dipropylene glycols); Avn K and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-butanediol, or 1,1'-oxydi-2-propanol (dipropylene glycols); Avn L, 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-butanediol, or 1,1'-oxydi-2-propanol (dipropylene glycols); or Avn R and 1,2-propanediol (propylene glycol), 1,2-butane Diol, 1,2-pentanediol (Hydrolite-5), 1,2-hexanediol Hydrolite-6, 1,2-heptanediol, 1,2-octanediol 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol 1,3-Butanediol (butylene glycol), 1,3-Propanediol, 1 ,4-butanediol, or 1,1'-oxydi-2-propanol (dipropylene glycols).

[0091] Particularly good combinations include: Avn A and 1,2-butanediol, 1,2-pentanediol (Hydroli te-5), 1,2-hexanediol (Hydrolite-6), 1,2-heptane Diol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol 1,3-propanediol or 1,1'- Oxydi-2-propanol (dipropylene glycol) combination; Avn B and 1,2-butanediol, 1,2-pentanediol (Hydrolit e-5), 1,2-Hexanediol (Hydrolite-6), 1,2-Heptanediol 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol; 1,3-propanediol; or 1,1'-o Combination of one or more of the following: 2-propanol (dipropylene glycol) Match; Avn C and 1,2-butanediol, 1,2-pentanediol (Hydroli te-5), 1,2-hexanediol (Hydrolite-6), 1,2-heptane Diol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol 1,3-propanediol or 1,1'- Oxydi-2-propanol (dipropylene glycol) combination; Avn G and 1,2-butanediol, 1,2-pentanediol (Hydroli te-5), 1,2-hexanediol (Hydrolite-6), 1,2-heptane Diol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol 1,3-propanediol or 1,1'- Oxydi-2-propanol (dipropylene glycol) combination; Avn H and 1,2-butanediol, 1,2-pentanediol (Hydroli te-5), 1,2-hexanediol (Hydrolite-6), 1,2-heptane Diol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol 1,3-propanediol or 1,1'- Oxydi-2-propanol (dipropylene glycol) combination; Avn K and 1,2-butanediol, 1,2-pentanediol (Hydroli te-5), 1,2-hexanediol (Hydrolite-6), 1,2-heptane Diol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol 1,3-propanediol or 1,1'- Oxydi-2-propanol (dipropylene glycol) combination; Avn L and 1,2-butanediol, 1,2-pentanediol (Hydroli te-5), 1,2-hexanediol (Hydrolite-6), 1,2-heptane Diol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol 1,3-propanediol or 1,1'- Oxydi-2-propanol (dipropylene glycol) combination; or Avn R and 1,2-butanediol, 1,2-pentanediol (Hydroli te-5), 1,2-hexanediol (Hydrolite-6), 1,2-heptane Diol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol 1,3-propanediol or 1,1'- Oxydi-2-propanol (dipropylene glycol) combination.

[0092] In a particularly preferred variant, the composition according to the first aspect of the invention comprises the following combinations: Contains one of: Avn A and 1,2-pentanediol (Hydrolite-5), 1,2-hex Sandiol (Hydrolite-6), 1,2-heptanediol, 1,2-octanediol in combination with one or more of 1,2-nonanediol, 1,3-nonanediol, or 1,2-nonanediol; Avn B and 1,2-pentanediol (Hydrolite-5), 1,2-hex Sandiol (Hydrolite-6), 1,2-heptanediol, 1,2-octanediol in combination with one or more of 1,2-nonanediol, 1,3-nonanediol, or 1,2-nonanediol; Avn C and 1,2-pentanediol (Hydrolite-5), 1,2-hex Sandiol (Hydrolite-6), 1,2-heptanediol, 1,2-octanediol in combination with one or more of 1,2-nonanediol, 1,3-nonanediol, or 1,2-nonanediol; Avn G and 1,2-pentanediol (Hydrolite-5), 1,2-hex Sandiol (Hydrolite-6), 1,2-heptanediol, 1,2-octanediol in combination with one or more of 1,2-nonanediol, 1,3-nonanediol, or 1,2-nonanediol; Avn H and 1,2-pentanediol (Hydrolite-5), 1,2-hex Sandiol (Hydrolite-6), 1,2-heptanediol, 1,2-octanediol in combination with one or more of 1,2-nonanediol, 1,3-nonanediol, or 1,2-nonanediol; Avn K and 1,2-pentanediol (Hydrolite-5), 1,2-hex Sandiol (Hydrolite-6), 1,2-heptanediol, 1,2-octanediol in combination with one or more of 1,2-nonanediol, 1,3-nonanediol, or 1,2-nonanediol; Avn L and 1,2-pentanediol (Hydrolite-5), 1,2-hex Sandiol (Hydrolite-6), 1,2-heptanediol, 1,2-octanediol or 1,2-nonanediol; Or Avn R and 1,2-pentanediol (Hydrolite-5), 1,2-hex Sandiol (Hydrolite-6), 1,2-heptanediol, 1,2-octanediol or 1,2-nonanediol.

[0093] In a particularly preferred variant, the composition according to the first aspect of the invention comprises the following combinations: Contains one of: Avn A in combination with 1,2-heptanediol; Avn B in combination with 1,2-heptanediol; Avn C in combination with 1,2-heptanediol; Avn G in combination with 1,2-heptanediol; Avn H in combination with 1,2-heptanediol; Avn K in combination with 1,2-heptanediol; Avn L in combination with 1,2-heptanediol; or A combination of Avn R and 1,2-heptanediol.

[0094] Due to the synergistic effect, in the most preferred variant, the composition according to the first aspect of the invention Contains any one of the following combinations: Avn A and a blend of 1,2-hexanediol + 1,2-octanediol combination; Avn B and a blend of 1,2-hexanediol + 1,2-octanediol combination; Avn C and a blend of 1,2-hexanediol + 1,2-octanediol combination; Avn G and a blend of 1,2-hexanediol + 1,2-octanediol combination; Avn H and a blend of 1,2-hexanediol + 1,2-octanediol combination; Avn K and a blend of 1,2-hexanediol + 1,2-octanediol combination; Avn L and a blend of 1,2-hexanediol + 1,2-octanediol combination; or Avn R and a blend of 1,2-hexanediol + 1,2-octanediol combination.

[0095] In a further most preferred variant, the composition according to the first aspect of the invention comprises the following combination: Contains one of: Avn A and a blend of 1,2-pentanediol + 1,2-heptanediol combination; Avn B with a blend of 1,2-pentanediol + 1,2-heptanediol combination; Avn C with a blend of 1,2-pentanediol + 1,2-heptanediol combination; Avn G and a blend of 1,2-pentanediol + 1,2-heptanediol combination; Avn H with a blend of 1,2-pentanediol + 1,2-heptanediol combination; Avn K and a blend of 1,2-pentanediol + 1,2-heptanediol combination; Avn L and a blend of 1,2-pentanediol + 1,2-heptanediol combination; or Avn R and a blend of 1,2-pentanediol + 1,2-heptanediol combination.

[0096] In a further most preferred variant, the composition according to the first aspect of the invention comprises the following combination: Contains one of: Avn A and a blend of 1,2-hexanediol + 1,2-heptanediol combination; Avn B and a blend of 1,2-hexanediol + 1,2-heptanediol combination; Avn C and a blend of 1,2-hexanediol + 1,2-heptanediol combination; Avn G and a blend of 1,2-hexanediol + 1,2-heptanediol combination; Avn H and a blend of 1,2-hexanediol + 1,2-heptanediol combination; Avn K and a blend of 1,2-hexanediol + 1,2-heptanediol combination; Avn L and a blend of 1,2-hexanediol + 1,2-heptanediol combination; or Avn R and a blend of 1,2-hexanediol + 1,2-heptanediol combination.

[0097] In a further most preferred variant, the composition according to the first aspect of the invention comprises the following combination: Contains one of: Avn A and a blend of 1,2-octanediol + 1,2-heptanediol combination; Avn B with a blend of 1,2-octanediol + 1,2-heptanediol combination; Avn C and a blend of 1,2-octanediol + 1,2-heptanediol combination; Avn G and a blend of 1,2-octanediol + 1,2-heptanediol combination; Avn H with a blend of 1,2-octanediol + 1,2-heptanediol combination; Avn K and a blend of 1,2-octanediol + 1,2-heptanediol combination; Avn L and a blend of 1,2-octanediol + 1,2-heptanediol combination; or Avn R and a blend of 1,2-octanediol + 1,2-heptanediol combination.

[0098] Avenanthramide B + 1,2-Hexanediol and 1,2-Octanediol (Oct ancediol) or avenanthramide L + 1,2-penta Hydrolite-5 or 1,2-Hexanediol (Hydrol The combination of ite-6) is particularly advantageous.

[0099] For example, a mixture of 1,2-hexanediol and 1,2-octanediol is used at 1%. When used together, it was more effective than 1,2-hexanediol when used alone at the same dose. As demonstrated in the following examples, this leads to a high permeability of avenanthramide B. , an 87% increase compared to 62%.

[0100] Particularly preferred mixtures according to the invention are those in which the composition comprises, based on the total weight of the composition: 0.0001 to 5.0% by weight, preferably 0.0005 to 2.0% by weight, More preferably, 0.001 to 1% by weight of avenanthramide A, B, C, D, E, F, G, H and L, and mixtures of these avenanthramides. At least one avenanthramide; and -0.01 to 10.0% by weight, preferably 0.5 to 7.0% by weight, more preferably 0.5 to 7.0% by weight or 0.1 to 5.0% by weight of at least one penetration enhancer It is a mixture comprising or consisting of:

[0101] The concentration of the penetration enhancer in the composition according to the present invention is at least one avenanthramide or The best osmotic effect is obtained when the concentration of the compound is significantly higher than that of its analogue. Particularly preferred mixtures according to this embodiment have a total amount of avenanthramide relative to the total amount of penetration enhancer. The weight ratio is between 1:100 and 1:1, preferably between 1:50 and 1:1, and particularly preferably The ratio is between 1:20 and 1:1.

[0102] The compositions according to the invention, particularly those characterized as preferred compositions, have a synergistically enhancing effect. The effectiveness of the composition is surprisingly improved by the incorporation of one or more amines. It is more effective than a composition containing only venanthramide. Combined avenanthramides A, B, C, D, E, F, G, H, L or mixtures thereof The permeability effect on the sclerotinic acid in combination with a permeation enhancer is demonstrated in the following examples. Even better than dihydroavenanthramide D.

[0103] Cosmetic or pharmaceutical active substances, namely avenans as specified above. Sulamido has very interesting biological benefits, e.g. anti-inflammatory, antioxidant, anti-pruritic, anti-irritant. Although these avenanthramides exhibit anti-atherogenic and anti-atherogenic activity, they are better absorbed by the stratum corneum. They are able to penetrate and thus better reach their intended targets. Thus, the composition according to the invention is suitable for skin care and scalp care or skin and scalp protection. and in the prevention and / or treatment of skin diseases.

[0104] The compositions according to the invention are also particularly effective and are effective in preventing any toxicological or dermatologically significant The composition does not contain any secondary components. Therefore, the composition is not useful in cosmetic or pharmaceutical preparations. can be used without further concern.

[0105] Generally, the substances used in the compositions and final preparations will be selected based on their activity and the concentrations relevant for administration. In the degree range, - should be toxicologically acceptable; - should be well tolerated by the skin, - it should be stable (especially in conventional formulations), - should preferably be odorless, and - It should be cheap to produce (i.e. using standard processes and / or (starting from standard precursors) Please keep this in mind.

[0106] These properties of the avenanthramides, in combination with the above-described properties of the penetration enhancers, Due to the excellent anti-inflammatory, antioxidant, anti-pruritic, anti-irritant and anti-atherogenic activities mentioned above The composition according to the present invention is useful for skin and scalp protection as well as skin and scalp care. and thus are beneficial for the prevention and / or treatment of skin diseases.

[0107] Thus, another aspect of the present invention relates to a cosmetic composition according to the first aspect of the present invention. In particular, skin protection and skin care, scalp protection and scalp care, hair care, and nail care or skin condition, intolerant or sensitive skin, skin irritation, skin redness, wheals, scratches Pruritus (itching), skin aging, wrinkle formation, loss of skin volume, loss of skin elasticity, pigmentation spots, discoloration For the prevention and / or treatment of dry skin, i.e. dry skin that requires skin moisturization Regarding use in.

[0108] Another aspect of the invention relates to a composition according to the first aspect of the invention for use as a medicament. do.

[0109] Due to its excellent properties as described above, the composition according to the first aspect of the present invention is suitable for treating skin diseases or corneal ulcers. Interstitial diseases, especially barrier-related inflammatory, immunoallergic, atherogenic, and dry or prevention and / or treatment of skin or keratinopathy having a hyperproliferative component is particularly useful in treatment.

[0110] Examples of such skin or keratin disorders include atopic dermatitis (neurodermatitis), dry skin, and Scabies, acneiform eruptions, asteatosis, xerosis, eczema, hyper- and hyposeborrhea, dermatitis, rosacea, erythema , pruritus, inflammation, irritation, fibrosis, lichen planus, pityriasis rosea, tinea versicolor, autoimmune blistering diseases These include skin rash, urticaria, angioedema, allergic skin reactions, wound healing, and tissue regeneration. can be.

[0111] In a particularly preferred variant, at least one avenanthramide or its derivatives according to the invention are Compositions containing analogs of the formula (I) are useful for preventing and / or treating pruritus (itch). It is useful.

[0112] Chronic pruritus is a common symptom associated with a variety of skin conditions and systemic diseases and may Chronic pruritus is characterized by clinical symptoms (e.g., inflammatory / inflammation) and is therefore not associated with a known underlying condition. Combined with the presence of inflammatory or normal / non-inflammatory skin and / or secondary scratch lesions and underlying causes (e.g., dermatologic, systemic, neurological, psychosomatic, mixed or They are classified according to their origin (uncertain origin).

[0113] Due to the specific antioxidant activity of avenanthramides, the present invention also provides a novel method for preventing and treating the increased ROS production. A composition according to the first aspect of the invention for use in the prevention and / or treatment of skin diseases. and / or the skin disease associated with increased ROS production is atopic dermatitis. , neurodermatitis, psoriasis, rosacea, acneiform rash, asteatosis and xerosis. The present invention relates to a composition comprising:

[0114] The use of avenanthramide or its analogues for each of these purposes has therapeutic value. Adding an effective amount of the substance or preparation imparts the respective therapeutic activity of the substance. This corresponds to a method for

[0115] In the context of the present invention, an effective amount of a composition is defined as the amount of each active ingredient, i.e., avenin and providing a benefit, e.g., a reduction in symptoms associated with the disorder, disease, or condition being treated. When applied to a combination or preparation, as in the present invention, , this term refers to the amount of combined active substances or ingredients that provides a benefit.

[0116] Thus, the present invention provides a method for treating a skin or keratinopathy in a subject in need thereof. The present invention relates to a method for preventing and / or treating a skin or keratinopathy, the method comprising administering to a subject a at least one avenanthramide or analogue thereof in an amount sufficient to administering a therapeutically effective amount of a composition comprising or consisting of one penetration enhancer. , relates to a method.

[0117] Another aspect of the present invention is a cosmetic composition for skin care, scalp care, nail care and hair care. and / or for the prevention and treatment of said skin conditions. and / or in the treatment and / or prevention of said skin or keratinopathy and and / or the use of a composition according to the first aspect of the invention in treatment.

[0118] In a preferred variant, the cosmetic or pharmaceutical preparation according to the invention contains Preferably, the content is 0.0001 to 10.0% by weight, more preferably 0.0005 to 5% by weight, and most preferably 0.0001 to 10.0% by weight. The composition according to the present invention is preferably contained in an amount of 0.001 to 1% by weight.

[0119] The composition according to the first aspect of the invention can be easily incorporated into conventional cosmetic or pharmaceutical products. can be done.

[0120] Within this context, cosmetic and / or pharmaceutical preparations containing the composition according to the invention are It may be conventional in composition and may be used in the context of dermatological or keratinological treatment or cosmetic care. may serve to treat the skin, scalp, hair and / or nails.

[0121] Preferred cosmetic and / or pharmaceutical preparations or products, e.g. active substances or cosmetic In order to produce a pharmaceutical or pharma- ceutically acceptable excipient, the composition according to the present invention may be and optionally further combining with synergistic enhancing or auxiliary substances; and together with these.

[0122] "Active agent" means a substance or compound that confers a primary utility to a composition or formulation. Examples of such active substances are antioxidants, preservatives, (metal) chelating agents, permeating agents, Promoting, anti-inflammatory, antibacterial or antifungal, redness-relieving or itching-relieving These include substances having a specific action, pain relieving substances or moisturizing agents.

[0123] "Excipient" means a substance used to formulate cosmetics or pharmaceuticals as a result of processing or manufacturing. This refers to an inert substance used in

[0124] Skin conditions or diseases are often characterized by dry skin, scratchy skin, skin lesions or These are accompanied by inflammation, and therefore, a composition or cosmetic comprising the composition according to the present invention and / or The pharmaceutical preparations particularly advantageously contain skin moisturizing and / or moisture-retaining substances, cooling agents, ointments, Sumolites, keratolytic substances, nutritional substances, anti-inflammatory substances, antibacterial or antifungal substances and and / or substances having redness-relieving or itching-relieving effects and / or analgesic substances. Also contains moisturizers and / or humectants.

[0125] Itching occurs with particular intensity when the skin is dry. Skin moisturization and / or hydration Use of the retention substance in cosmetic and / or pharmaceutical preparations significantly relieves itching. Thus, the composition or cosmetic and / or pharmaceutical preparation according to the invention It is also particularly advantageously combined with one or more skin moisturizing and / or moisture retaining substances. Therefore, the composition or cosmetic and / or pharmaceutical composition according to the present invention can be used The preparations may also advantageously contain the following moisturizing and / or hydrating substances: Sodium lactate, urea, urea derivatives, alcohol, glycerol, diols, etc. For example, propylene glycol, hexylene glycol, 1,2-pentanediol, 1,2 -Hexanediol, 1,2-heptanediol, 1,2-octanediol, 1,2- nonanediol, 1,2-decanediol or a mixture of said diols, in particular 1,2-hexanediol A mixture of xanediol and 1,2-octanediol, collagen, elastin or Contains hyaluronic acid, diacyl adipate, petrolatum, urocanic acid, lecithin, panthenoic acid, ol, phytantriol, lycopene, (pseudo)ceramide, glycosphingolipid, Lactosterol, phytosterol, chitosan, chondroitin sulfate, lanolin, lanolin Esters, amino acids, alpha hydroxy acids (e.g., citric acid, lactic acid, malic acid) and and their derivatives, monosaccharides, disaccharides and oligosaccharides, e.g., glucose, galactose, fructose, Lactose, mannose, fructose and lactose, polysugars such as R- Glucans, especially 1,3-1,4-β-glucan from oats, alpha-hydroxy fats Fatty acids, triterpene acids such as betulinic acid or ursolic acid, and algae extracts.

[0126] Depending on the substance, the concentration of the water retention regulator used is optimal for ready-to-use cosmetic or pharmaceutical applications. It is between 0.1 and 10% (m / m) based on the total weight of the final product, preferably between 0.5 and 5% (m / m). These data are especially relevant for the diols which are advantageously used. For example, hexylene glycol, 1,2-pentanediol, 1,2-hexanediol 1,2-octanediol and 1,2-decanediol, as well as 1,2-hexanediol. This applies to a mixture of 1,2-octanediol and 1,2-octanediol.

[0127] The use of cooling agents in cosmetic and pharmaceutical preparations can relieve itching. The compositions or cosmetic and / or pharmaceutical preparations according to the invention are therefore particularly advantageous The composition may be combined with one or more cooling agents. Preferred individual cooling agents for use are listed below; those skilled in the art will recognize many others. can be added to this list; the listed cooling agents may be combined with each other. They can also be used as: l-menthol, d-menthol, racemic menthol, menthol Glycerol acetal (trade name: Frescolat(R) MGA), methyl lactate Menthyl lactate (trade name: Frescolat® ML; menthyl lactate is preferably l- Menthyl lactate, especially l-menthyl l-lactate, substituted menthyl-3-carboxylates amides (e.g., menthyl-3-carboxylic acid N-ethylamide), 2-isopropyl-N -2,3-trimethylbutanamide, substituted cyclohexanecarboxamide, 3-menthoxy Menthoxypropane-1,2-diol, 2-hydroxyethyl Menthyl carbonate, 2-hydroxypropyl menthyl carbonate, N-acetyl Glycine menthyl ester, isopulegol, hydroxycarboxylic acid menthyl ester (e.g., menthyl 3-hydroxybutyrate), monomenthyl succinate, 2-mercapto Tricyclodecanone, Menthyl 2-pyrrolidin-5-one carboxylate, 2,3-dihydro Hydroxy-p-menthane, 3,3,5-trimethylcyclohexanone glycerol ketate 3-menthyl-3,6-di- and trioxaalkanoates, 3-menthyl methoxides cyacetate and icilin.

[0128] Due to their specific synergistic effects, the preferred cooling agents are l-menthol, d-menthol, , racemic menthol, menthone glycerol acetal (trade name: Frescolat ( (registered trademark) MGA), menthyl lactate (preferably l-menthyl lactate, especially l-menthyl l -lactate (trade name: Frescolat® ML), substituted menthyl-3- Carboxamides (e.g., menthyl-3-carboxylic acid N-ethylamide), 2-isopropanol Pyr-N-2,3-trimethylbutanamide, Substituted cyclohexanecarboxamide, 3- Menthoxypropane-1,2-diol, 2-hydroxyethyl menthyl carbonate, 2-hydroxypropyl menthyl carbonate and isopulegol.

[0129] Particularly preferred cooling agents are l-menthol, racemic menthol, menthone glycerol Acetal (trade name: Frescolat® MGA), menthyl lactate (preferred or l-menthyl lactate, especially l-menthyl l-lactate (trade name: Frescolat (registered trademark) ML)), 3-menthoxypropane-1,2-diol, 2-hydroxyethyl 2-Hydroxypropylmenthyl carbonate and 2-hydroxypropylmenthyl carbonate.

[0130] Very particularly preferred cooling agents are l-menthol, menthone glycerol acetal ( Trade name: Frescolat® MGA) and menthyl lactate (preferably l- Menthyl lactate, especially l-menthyl l-lactate (trade name: Frescolat®) The mark is ML.

[0131] Depending on the substance, the concentration of the freshener used may vary depending on the composition of the ready-to-use cosmetic or pharmaceutical product. Preferably, the content is between 0.01 and 20% by weight, more preferably between 0.1 and 20% by weight, based on the total weight of the composition. 5% by weight.

[0132] The composition or cosmetic and / or pharmaceutical preparation according to the invention may also comprise one or more It can also be used with any of the osmolytes mentioned here. Examples of phosphates include sugar alcohols (myo-inositol, mannitol, sorbitol), Quaternary amines, such as taurine, choline, betaine, betaine glycine, ectoine, diamine Glycerol phosphate, phosphorylcholine or glycerophosphorylcholine, amino Acids, such as glutamine, glycine, alanine, glutamate, aspartate or protamine phosphatidylcholine, phosphatidylinositol, inorganic phosphate, and Polymers of the above compounds, such as proteins, peptides, polyamino acids and polyols, The following substances are included in the group: All osmolytes simultaneously have a skin moisturizing effect.

[0133] Preferably, keratolytic substances can also be combined with the preparations according to the invention. Solubilizing compounds include the large group of alpha hydroxy acids, e.g., salicylic acid is preferably used.

[0134] For example, for the topical cosmetic or pharmaceutical treatment of dry and / or itchy skin; In cosmetic and / or pharmaceutical preparations containing the composition according to the invention, the proportion is particularly high. Nutrients such as glyceryl phosphate are also particularly effective in reducing transepidermal water loss due to lipophilic components. In a preferred embodiment, the cosmetic and / or pharmaceutical preparation comprises one or Multi-nutritional animal and / or vegetable fats and oils, e.g. olive oil, corn oil, Hemp oil, refined soybean oil, palm oil, sesame oil, rapeseed oil, almond oil, borage oil , evening primrose oil, coconut oil, shea butter, jojoba oil, sperm whale oil, tallow, cow's foot oil and lard, and optionally other nutritious components, e.g., 8 to 30 C As used herein, fatty alcohols include those having a saturated or unsaturated and either linear or branched. Nutrients that can be particularly preferably combined with the mixture also include, in particular, ceramides. Ceramides are N-acylsulfans that significantly improve the water retention capacity of the stratum corneum. gosine (a fatty acid amide of sphingosine) or synthetic analogues of such lipids (so-called pseudoceramides); phospholipids, such as soybean lecithin, egg lecithin and cephalin; and vaseline, paraffin oil and silicone oil, Among others, the authors have described dialkyl- and alkylaryl siloxanes, e.g., dimethylpolysiloxanes. and methylphenylpolysiloxanes and their alkoxylated and quaternary Includes substituted derivatives.

[0135] The composition or cosmetic and / or pharmaceutical preparation according to the invention may also comprise one or more Contains multiple anti-inflammatory and / or redness-relieving and / or itching-relieving substances It may contain other substances, in this context, which relieve redness and itching, and are cosmetic and and / or any anti-inflammatory agent suitable and / or conventionally used for use in skin diseases. Steroidal anti-inflammatory substances of the corticosteroid class. , e.g., hydrocortisone, hydrocortisone derivatives, e.g., hydrocortisone 17 -butyrate, dexamethasone, dexamethasone phosphate, methylprednisolone or Cortisone is an anti-inflammatory compound or a compound that relieves redness and / or itching. Other steroidal anti-inflammatory agents may be added to this list. It is also possible to use non-steroidal anti-inflammatory drugs. Examples that can be mentioned here are oxicams, such as piroxicam or tenoxicam; salicylates, such as Aspirin, Disalcid®, Solprin® or Phenol dosal; acetic acid derivatives such as diclofenac, fenclofenac, indomethacin, Sulindac, tolmetin or clindanac; fenamic acids, such as mefenamic acid, mefenamic acid lofenamic acid, flufenamic acid or niflumic acid; propionic acid derivatives, such as ibuprap or pyrazoles, e.g. phenoxaprofen, naproxen or benoxaprofen; Examples include nilbutazone, oxyphenylbutazone, febuxozone, and azapropazone. Possible alternatives include natural anti-inflammatory substances or substances that relieve redness and / or itching. The key is to use plant extracts, special highly active plant extract fractions, and even plant extracts. High purity active substances isolated from chamomile, aloe vera, and other herbs are particularly preferred. Loe vera, Commiphora species, Rubia species, willow, willow grass, oats, moss Rendula, Arnica, St. John's Wort, Honeysuckle, Rosemary, Pa ssiflora incarnata, witch hazel, ginger or echinacea Extracts, fractions and active substances derived therefrom, as well as pure substances, such as, inter alia, (alpha-) Bisabolol, Apigenin, Apigenin-7-glucoside, Boswellic Acid, Phytosterol glycyrrhizin, glabridin, gingerol, e.g., [6]-gingerol, Paradols, e.g., [6]-paradol and licochalcone A. These preparations are It is also possible to contain a mixture of two or more anti-inflammatory active compounds.

[0136] Depending on the substance, the concentration of anti-inflammatory compounds that can be used varies from ready-to-use cosmetic products to or between 0.005 and 2% (m / m) based on the total weight of the final pharmaceutical product, preferably These data are specifically for bisabolol. Applies.

[0137] Other antibacterial or antifungal active substances may also be used in the compositions or cosmetic products according to the invention and / or They can be used particularly advantageously in cosmetic and / or pharmaceutical preparations. Any antibacterial or antifungal active substance suitable or customary for use on the In addition to the large group of conventional antibiotics, other products which are advantageous here include, for example, in particular Triclosan, Climbazole, Octoxyglycerin, Octirox (registered trademark) )(1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H )-Pyridone 2-aminoethanol salt), chitosan, farnesol, monolauric acid glycerin glycerol or a combination of said substances, which are particularly effective in treating underarm odor, foot odor, Or used against dandruff.

[0138] The composition or cosmetic and / or pharmaceutical preparation according to the invention may also comprise one or more It may contain a number of analgesic substances and is suitable or suitable for cosmetic and / or pharmaceutical use. Any conventional analgesic substance, such as alpha-bisabolol, azulene, guaiazum 18-β-glycyrrhetinic acid, laureth-9, trideceth-9, 4-t-butyl silyl Cyclohexanol can be used.

[0139] The composition or cosmetic and / or pharmaceutical preparation according to the invention may also comprise one or more A number of cosmetically or pharma- ceutically acceptable excipients, e.g., those conventionally used in such preparations, may be used. used in the past, e.g. antioxidants, preservatives, (metal) chelating agents, surfactants Fatty acids, emulsifiers, perfume oils, defoamers, colorants, pigments with coloring action, thickeners, plasticizers, fats, oils , waxes or other conventional components of cosmetic formulations, such as alcohols, polyols, It can be combined with polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives. Suitable or traditionally used in cosmetic and / or pharmaceutical applications. Any conceivable antioxidants, preservatives, (metal) chelating agents, surfactants, emulsifiers, Perfume oils, defoamers, colorants, pigments with coloring action, thickeners, plasticizers, fats, oils, waxes, or other conventional components of cosmetic or pharmaceutical formulations, e.g. alcohols, polyols , polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives according to the invention It can be used.

[0140] The composition or cosmetic and / or pharmaceutical preparation according to the invention is also particularly advantageously It may contain one or more antioxidants and is suitable for cosmetic and / or pharmaceutical applications. Any antioxidant suitable or conventionally used in the art may be used. In the 1990s, antioxidants were found in the amino acids (e.g., glycine, histidine, tyrosine, tryptophan, etc.) ) and derivatives thereof, imidazoles (e.g. urocanic acid) and derivatives thereof, Peptides, such as D,L-carnosine, D-carnosine, L-carnosine and the like Derivatives of carotenoids (e.g. anserine), carotenoids, carotenes (e.g. α-carotene, β-carotene) lycopene, lycopene) and their derivatives, lipoic acid and its derivatives (e.g. dihydrolipid thioglucose, propylthiouracil and other thiols (e.g., thiol Doxin, glutathione, cysteine, cystine, cystamine and their glycosyl , N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl yl, oleyl, gamma-linoleyl, cholesteryl and glyceryl esters) and Salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionate Pionic acids and their derivatives (esters, ethers, peptides, lipids, nucleotides, Nucleosides and salts) and sulfoximine compounds (e.g. buthionine sulfoximine Homocysteine ​​sulfoximine, buthionine sulfone, penta-, hexa-, hepta -Thionine sulfoximine) (these are tolerated at very low doses), and also (metals) Chelating agents, such as alpha-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin , α-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acids, bile extract substances, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fats acids and their derivatives (e.g., gamma-linolenic acid, linoleic acid, oleic acid), folic acid and and their derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and Its derivatives (e.g., ascorbyl palmitate, magnesium ascorbyl phosphate, scorbyl acetate), tocopherols and their derivatives (e.g., vitamin E acetate, acetate), vitamin A and its derivatives (e.g., vitamin A palmitate), and Coniferyl benzoate of benzoin resin, rutinic acid and its derivatives, ferulic acid (f errulic acid) and its derivatives, butylhydroxytoluene, butyl hyd Nordihydroguaiacinic acid, Nordihydroguaiaretic acid, Tri Hydroxybutyrophenone, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (e.g., ZnO, ZnSO4), selenium and its derivatives (e.g., Se methionine), stilbene and their derivatives (e.g., stilbene oxide, t trans-stilbene oxide), as well as derivatives of the active compounds (e.g., salts, estilbene oxides, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids), e.g. It is selected from the group consisting of those which are suitable according to the invention.

[0141] The composition or cosmetic and / or pharmaceutical preparation according to the invention is also particularly advantageously It may contain one or more substances for preservation purposes and may be cosmetic and / or pharmaceutical Suitable or customary for pharmaceutical use, advantageously, for example, benzoic acid, its esters, among others. and its salts;Propionic acid and its salts;Salicylic acid and its salts;2,4-Hexanoic acid (Sorbic acid) and its salts; Formaldehyde and paraformaldehyde; 2-Hydroformaldehyde Roxybiphenyl ether and its salts; 2-Zinc sulfidopyridine N-oxide; Organic sulfites and bisulfites; Sodium iodate; Chlorobutanol; 4-hydroxybutanol Benzoic acid and its salts and esters; Dehydroacetic acid; Formic acid; 1,6-bis(4-amino (2-bromophenoxy)-n-hexane and its salts;Ethylmercury-(II)-thio Sodium salts of salicylic acid; Phenylmercury and its salts; 10-Undecylenic acid and Its salts; 5-amino-1,3-bis(2-ethylhexyl)-5-methylhexahydropi 5-Bromo-5-nitro-1,3-dioxane;2-Bromo-2-nitro-1,3-dioxane ,3-Propanediol;2,4-Dichlorobenzyl alcohol;N-(4-chlorophen 4-Chloro-m-cresol;2-(4-chlorophenyl)urea; ,4,4'-Trichloro-2'-hydroxy-diphenyl ether;4-Chloro-3,5 -Dimethylphenol;1,1'-methylene-bis(3-(1-hydroxymethyl-2, 4-dioxyimidazolidin-5-yl)urea; poly(hexamethylene biguanide) ) hydrochloride;2-phenoxyethanol;Hexamethylenetetramine;1-(3-chloroa 1-(4-Chloro)-3,5,7-triaza-1-azoniaadamantane chloride; -phenoxy)-1(1H-imidazol-1-yl)-3,3-dimethyl-2-butano 1,3-Bis(hydroxymethyl)-5,5-dimethyl-2,4-imidazolidinediamine benzyl alcohol; Octopirox®; 1,2-dibromo-2, 4-Dicyanobutane; 2,2'-methylene-bis(6-bromo-4-chloro-phenol) );Bromochlorophene;5-chloro-2-methyl-3(2H)-isothiazolinone and and 2-methyl-3(2H)isothiazolinone with magnesium chloride and magnesium nitrate. 2-Benzyl-4-chlorophenol;2-Chloroacetamide;Chlorohe xidine; chlorhexidine acetate; chlorhexidine gluconate; chlorhexidine hydrochloride ;1-Phenoxy-propan-2-ol;N-Alkyl(C12-C22)trimethyl Ammonium bromide and N-alkyl (C12-C22) trimethylammonium chloride 4,4-Dimethyl-1,3-oxazolidine;N-Hydroxymethyl-N-(1 ,3-Di(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl)-N'- Hydroxymethylurea; 1,6-bis(4-amidinophenoxy)-n-hexane and and its salts;Glutaraldehyde 5-ethyl-1-aza-3,7-dioxabicyclo(3. 3.0) Octane; 3-(4-chlorophenoxy)-1,2-propanediol; High amine;alkyl(C8-C18)dimethylbenzylammonium chloride;alkyl(C 8~C18) dimethylbenzylammonium bromide; alkyl(C8~C18) dimethyl Benzylammonium saccharinate; Benzylhemiformal; 3-iodo-2-propane or sodium ((hydroxymethyl)amino)acetate Any preservative selected from the group consisting of preservatives such as acetaminophen, ...

[0142] The composition or cosmetic and / or pharmaceutical preparation according to the invention is also particularly advantageously It may contain one or more (metal) chelating agents and may be used in cosmetic and / or pharmaceutical applications. Any metal chelating agent suitable or conventional for the intended application may be used. As metal chelating agents, α-hydroxy fatty acids, phytic acid, lactoferrin, α - hydroxy acids, such as, inter alia, citric acid, lactic acid and malic acid, as well as humic acid, bile acid bile extract, bilirubin, biliverdin or EDTA, EGTA and Derivatives are also included.

[0143] The composition or cosmetic and / or pharmaceutical preparation may also be, in particular, crystalline or microcrystalline If solids, such as inorganic micropigments, are incorporated into the preparation, it is particularly advantageous to use one or more containing anionic, cationic, nonionic and / or amphoteric surfactants of Surfactants are amphiphilic substances that can solubilize organic, non-polar substances in water. The hydrophilic portion of a surfactant molecule usually contains a polar functional group, e.g., -COO - , -OSO 3 - or -SO3 - whereas the hydrophobic moiety is usually a non-polar hydrocarbon group. Surfactants are generally classified according to the type and charge of the hydrophilic portion of the molecule. Three groups: anionic surfactants, cationic surfactants; amphoteric surfactants; and nonionic surfactants. It can be divided into carboxylic acid surfactants.

[0144] Anionic surfactants usually contain carboxylate, sulfate or sulfonate groups. In aqueous solution, they form organic imines that are negatively charged in acidic or neutral media. Cationic surfactants are essentially exclusively composed of quaternary ammonium groups. In aqueous solution, they are characterized by the presence of positively charged organic They form ions. Amphoteric surfactants contain both anionic and cationic groups, and Thus, depending on the pH value, they behave like anionic or cationic surfactants in aqueous solution. They carry a positive charge in a strongly acidic medium and a negative charge in an alkaline medium. In the neutral pH range, by contrast, they are zwitterions. A typical example of a surfactant is a nonionic surfactant, which does not form ions in aqueous media.

[0145] Anionic surfactants which can be used advantageously include: acyla amino acids (and their salts), e.g., acyl glutamates, e.g., acyl glutamic acid Sodium, Di-TEA-Palmitoyl Aspartate and Caprylic / Capric Glycol sodium glutamate; acyl peptides, e.g. palmitoyl hydrolyzed milk protein, co Sodium Cocoyl Hydrolyzed Soy Protein and Sodium Cocoyl Hydrolyzed Collagen Calcium / potassium; Sarcosinates, e.g., myristoyl sarcosine, lauroyl sarcosine TEA, sodium lauroyl sarcosinate and sodium cocoyl sarcosinate; taurates, such as sodium lauroyl taurate and sodium methyl cocoyl taurate acyl lactylate, for example lauroyl lactylate and caproyl lactylate; Laninates; carboxylic acids and derivatives, e.g., lauric acid, aluminum stearate , magnesium alkanolates and zinc undecylates; ester carboxylic acids, e.g. Calcium Stearoyl Lactylate, Laureth-6 Citrate and PEG-4 Laureth Sodium myrocarboxylate; ether carboxylic acids, such as sodium laureth-13 carboxylate sodium and sodium PEG-6 cocamide carboxylate; phosphate esters and salts, e.g. For example, DEA-oleth-10 phosphate and dilaureth-4 phosphate; sulfonic acids and Salts, e.g., acyl isethionates, e.g., sodium / ammonium cocoyl isethionate alkyl aryl sulfonates; alkyl sulfonates, e.g., coco monoglycerides Sodium sulfonate, Sodium olefin (C12-14) sulfonate, Lauryl sulfonate Sodium fumarate and PEG-3 cocamide magnesium sulfate; sulfosuccinates, e.g. For example, dioctyl sodium sulfosuccinate, disodium laureth sulfosuccinate, Disodium Lauryl Sulfosuccinate and Undecylenamide MEA-2 sodium; and sulfates, e.g., alkyl ether sulfates, e.g., laureth sulfate. Sodium Laureth Sulfate, Ammonium Laureth Sulfate, Magnesium Laureth Sulfate, M Laureth Sulfate IPA, TIPA Laureth Sulfate, Sodium Myreth Sulfate and C12-13 Sodium Pareth Sulfate and alkyl sulfates, such as sodium lauryl sulfate, ammonium lauryl sulfate, Sodium and TEA Lauryl Sulfate.

[0146] Cationic surfactants which can be advantageously used include alkylamines, alkyl Imidazole, Ethoxylated Amine and Quaternary Surfactants: RNH2CH2CH2COO - (at pH 7); RNHCH2CH2COO - B + (at pH 12) (wherein B + is any cation, For example, Na + is); Esterquats are examples.

[0147] Quaternary surfactants are surfactants that contain at least one alkyl group covalently bonded to four alkyl or aryl groups. Contains N atoms, which results in a positive charge regardless of the pH value. Alkyl betaines, Alkylamidopropyl betaine and alkylamidopropyl hydroxysulfane ( The cationic surfactant used is preferably Also preferred are the group of quaternary ammonium compounds, in particular benzyltrialkylammonium chlorides. ammonium or benzyltrialkylammonium bromide, for example benzyldimethylsulfonium chloride Tearyl ammonium, as well as alkyl trialkyl ammonium salts, such as cetearyl chloride. Cetyltrimethylammonium bromide or cetyltrimethylammonium bromide, alkyldichloride Methyl hydroxyethyl ammonium or alkyl dimethyl hydroxyethyl ammonium bromide ammonium, dialkyldimethylammonium chloride or dialkyldimethylammonium bromide ammonium, alkylamidoethyltrimethylammonium ether sulfate, alkylpi pyridinium salts, such as laurylpyridinium chloride or cetylpyridinium chloride, imidazolium chloride, Zoline derivatives and compounds of cationic nature, such as amine oxides, e.g. alkyl Selected from alkyl dimethylamine oxide or alkylaminoethyl dimethylamine oxide Cetyltrimethylammonium salts can be used with particular advantage. .

[0148] Amphoteric surfactants which can be advantageously used include acyl / dialkylethylene diamines. amines, such as sodium acylamphoacetate, disodium acylamphodipropionate, Disodium alkylamphodiacetate, sodium amphohydroxypropyl acylsulfonate um, disodium acylamphodiacetate and sodium acylamphopropionate;N -Alkylamino acids, e.g. aminopropyl alkylglutamides, alkylaminopropyl ionic acid, sodium alkylimidodipropionate and lauroamphocarboxyglyceryl Nate is one example.

[0149] Nonionic surfactants which can be advantageously used are: alcohols; alkanols Amides, e.g. cocamide MEA / DEA / MIPA, amine oxides, e.g. cocoa amidopropylamine oxide; ethylene oxide of carboxylic acids, glycerol, sorbitan or or other alcohols; ethers, e.g. Ethoxylated / propoxylated alcohols, ethoxylated / propoxylated esters, ethoxylated / propoxylated propoxylated glycerol esters, ethoxylated / propoxylated cholesterol, ethoxy Ethoxylated / Propoxylated Triglyceride Esters, Ethoxylated / Propoxylated Lanolin, Ethoxylated Siliconized / propoxylated polysiloxane, propoxylated polyoxyethylene (POE) ether alkyl and alkyl polyglycosides, such as lauryl glucoside, decyl glucoside and and coconut glycosides; sucrose esters and ethers; polyglycerol esters, diglycerol Glycerol esters, monoglycerol esters; methyl glucose esters, hydro Examples of the esters include esters of hydroxy acids.

[0150] Anionic and / or amphoteric surfactants and one or more nonionic surfactants The use of a combination with is also advantageous.

[0151] The surfactant may be present in the composition or in the cosmetic and / or pharmaceutical preparation according to the invention. , can be present in a concentration between 1 and 98% (m / m) relative to the total weight of the formulation.

[0152] The composition or cosmetic and / or pharmaceutical preparation is also particularly advantageously a cosmetic or The present invention includes one or more emulsifiers commonly used in the art for preparing pharmaceutical formulations. The oil-in-water (O / W) emulsifier can be, for example, a polyethoxylated or Polypropoxylated or polyethoxylated and polypropoxylated products, e.g., fats Fatty alcohol ethoxylate, ethoxylated wool wax alcohol, general formula RO- (-CH2-CH2-O-) n -R' polyethylene glycol ether, general formula RC OO-(-CH2-CH2-O-) n -H fatty acid ethoxylates of the general formula R-COO- (-CH2-CH2-O-) n -R' etherified fatty acid ethoxylates of general formula RC OO-(-CH2-CH2-O-) n -C(O)-R' esterified fatty acid ethoxylate Polyethylene glycol glycerol fatty acid ester, ethoxylated sorbitan ester Cholesterol ethoxylate, ethoxylated triglyceride, general formula R-COO-( -CH2-CH2-O-) n -OOH (wherein n is a number from 5 to 30) Terephthalic acid, polyoxyethylene sorbitol fatty acid ester, general formula RO-(- CH2-CH2-O-) n Alkyl ether sulfates of the formula RO-(-SO3-H CH2-CH(CH3)-O-) n -H, aliphatic alcohol propoxylates of the general formula R -O-(-CH2-CH(CH3)-O-) n -R' Polypropylene glycol ether , Propoxylated Wool Wax Alcohol, Etherified Fatty Acid Propoxylate RC OO-(-CH2-CH(CH3)-O-) n -R', general formula R-COO-(-CH2- CH(CH3)-O-) n -C(O)-R' esterified fatty acid propoxylates, generally Formula R-COO-(-CH2-CH(CH3)-O-)n -H fatty acid propoxylates, Polypropylene glycol glycerol fatty acid ester, propoxylated sorbitan ester Cholesterol propoxylate, propoxylated triglyceride, general formula RO-( -CH2-CH(CH3)-O-) n -CH2-COOH alkyl ether carboxylic acid , general formula RO-(-CH2-CH(CH3)-O-) n -SO3-H alkyl ether sulfates (and acids based on these sulfates), with the general formula ROX n -Y m - H fatty alcohol ethoxylates / propoxylates, general formula ROX n -Y n - R' is a polypropylene glycol ether of the general formula R-COO-X n -Y n -R'A Ternated fatty acid propoxylates, and the general formula R-COO-X n -Y m -H fatty acid ethoxylate The alkoxylates / propoxylates can advantageously be selected from the group comprising:

[0153] According to the invention, the polyethoxylated or polypropoxylated or polyethoxylated The propoxylated and polypropoxylated O / W emulsifiers are those in which the O / W emulsifier contains the saturated groups R and R' If it contains, it has an HLB value of 11 to 18, more particularly preferably 14.5 to 15.5. It is particularly advantageous to select from the group consisting of substances in which the O / W emulsifier comprises unsaturated radicals R and / or R' When the isoalkyl derivative is present, the preferred emulsifier is The HLB value may also be lower or higher. Ethoxylated stearyl alcohol, cetyl alcohol and cetylstearyl alcohol Advantageously, the copolymer is selected from the group comprising cetearyl alcohol (cetearyl alcohol).

[0154] The following emulsifiers are particularly preferred: polyethylene glycol (13) stearyl ether ( Steareth-13), Polyethylene Glycol (14) Stearyl Ether (Steareth -14), polyethylene glycol (15) stearyl ether (steareth-15), Polyethylene glycol (16) stearyl ether (steareth-16), polyethylene Glycol (17) Stearyl Ether (Steareth-17), Polyethylene Glycol (18) Stearyl ether (steareth-18), polyethylene glycol (19) Stearyl ether (steareth-19), polyethylene glycol (20) stearyl Ether (steareth-20), polyethylene glycol (12) isostearyl ether (Isostearyl ether) Polyethylene glycol (13) isostearyl ether (Isostearyl ether-13), polyethylene glycol (14) isostearyl ether ( Isostearate-14), Polyethylene glycol (15) Isostearyl ether (I Sosteareth-15), Polyethylene Glycol (16) Isostearyl Ether (Iso Steareth-16), Polyethylene Glycol (17) Isostearyl Ether (Isostearyl Ether) Teareth-17), polyethylene glycol (18) isostearyl ether (isostearyl Areth-18), polyethylene glycol (19) isostearyl ether (isostearyl RES-19), Polyethylene Glycol (20) Isostearyl Ether (Isostearyl (ceteth-20), polyethylene glycol (13) cetyl ether (ceteth-13), polyethylene Ethylene glycol (14) Cetyl ether (ceteth-14), polyethylene glycol ( 15) Cetyl ether (ceteth-15), polyethylene glycol (16) Cetyl ether Cetyl ether (ceteth-16), polyethylene glycol (17), cetyl ether (ceteth-17) , Polyethylene glycol (18) cetyl ether (ceteth-18), polyethylene glycol Cole (19) Cetyl Ether (Ceteth-19), Polyethylene Glycol (20) Cetyl Cetyl ether (Ceteth-20), polyethylene glycol (13) isocetyl ether (Iso Isoceteth-13), Polyethylene Glycol (14) Isocetyl Ether (Isoceteth- 14), polyethylene glycol (15) isocetyl ether (isoceteth-15), Triethylene glycol (16) isocetyl ether (isoceteth-16), polyethylene Glycol (17) Isocetyl ether (Isoceteth-17), polyethylene glycol (18) Isocetyl ether (Isoceteth-18), polyethylene glycol (19) Isocetyl Ether (Isoceteth-19), Polyethylene Glycol (20) Isocetyl Ether (Isoceteth-20), Polyethylene Glycol (12) Oleyl Ether (Oleyl (12), polyethylene glycol (13) oleyl ether (oleth-13), poly Ethylene glycol (14) oleyl ether (oleth-14), polyethylene glycol (15) Oleyl ether (oleth-15), polyethylene glycol (12) lauryl Laureth-12, Polyethylene Glycol (12) Isolauryl Ether (Isolaureth-12), Polyethylene Glycol (13) Cetyl Stearyl Ether ( Ceteareth-13, Polyethylene glycol (14) Cetyl stearyl ether (cete Areth-14), polyethylene glycol (15) cetyl stearyl ether (cetearyl -15), polyethylene glycol (16) cetyl stearyl ether (ceteareth- 16), polyethylene glycol (17) cetyl stearyl ether (ceteareth-17 ), polyethylene glycol (18) cetyl stearyl ether (ceteareth-18), Polyethylene glycol (19) cetyl stearyl ether (ceteareth-19) and Polyethylene glycol (20) cetyl stearyl ether (ceteareth-20).

[0155] The fatty acid ethoxylates are also advantageously selected from the following group: polyethylene glycols (20) Stearates, polyethylene glycol (21) Stearates, polyethylene glycol Recall (22) Stearates, polyethylene glycol (23) Stearates, polyethylene Polyethylene glycol (24) stearate, polyethylene glycol (25) stearate , Polyethylene glycol (12) Isostearate, Polyethylene glycol (13) Isostearate, polyethylene glycol (14) Isostearate, polyethylene glycol Recall (15) Isostearate, Polyethylene Glycol (16) Isostearate , Polyethylene glycol (17) Isostearate, Polyethylene glycol (18) Isostearate, polyethylene glycol (19) Isostearate, polyethylene glycol Recall (20) Isostearate, Polyethylene Glycol (21) Isostearate , Polyethylene glycol (22) Isostearate, Polyethylene glycol (23) Isostearate, Polyethylene Glycol (24) Isostearate, Polyethylene Glycol Recall (25) Isostearate, Polyethylene Glycol (12) Oleate, Poly Ethylene glycol (13) oleate, polyethylene glycol (14) oleate, Polyethylene glycol (15) oleate, polyethylene glycol (16) oleate oleate, polyethylene glycol (17) oleate, polyethylene glycol (18) oleate oleate, polyethylene glycol (19) oleate and polyethylene glycol (2 0) Ore Art.

[0156] Sodium laureth-11 carboxylate is used as an ethoxylated alkyl ether carboxylic acid or can be advantageously used as its salt. Sodium laureth-14 sulfate is an alkyl It can be advantageously used as the ether sulfate. Lesteryl ether can be advantageously used as an ethoxylated cholesterol derivative. Polyethylene glycol (25) soy sterols have also proven useful.

[0157] Polyethylene glycol (60) evening primrose glyceride is an ethoxylated triglyceride. It can be advantageously used as

[0158] Polyethylene glycol glycerol fatty acid esters are also polyethylene glycol (20) Glyceryl laurate, polyethylene glycol (21) Glyceryl laurate , Polyethylene glycol (22) Glyceryl laurate, Polyethylene glycol (2 3) Glyceryl laurate, polyethylene glycol (6) (caprylic acid / capric acid) Glyceryl, Polyethylene Glycol (20) Glyceryl Oleate, Polyethylene Glycol Cole (20) Glyceryl Isostearate and Polyethylene Glycol (18) (O Advantageously, the fatty acids are selected from the group comprising glyceryl oleate / cocoate.

[0159] Sorbitan esters are also available as polyethylene glycol (20) sorbitan monolaurate. Sorbitan monostearate, polyethylene glycol (20) Cholesterol (20) sorbitan monoisostearate, polyethylene glycol (20) mono Sorbitan palmitate and polyethylene glycol (20) sorbitan monooleate Advantageously, it is selected from the group comprising:

[0160] As advantageous W / O emulsifiers the following can be used: aliphatic alcohols; saturated and Monoglycerol esters of unsaturated, branched and / or unbranched alkane carboxylic acids ter; saturated and / or unsaturated with a chain length of 8 to 24, especially 12 to 18, C atoms , diglycerol esters of branched and / or unbranched alkane carboxylic acids; 8 to 24 In particular saturated and / or unsaturated, branched and / or unsaturated alkyl chains with a chain length of 12 to 18 C atoms. Monoglycerol ethers of branched or unbranched alcohols; 8-24, especially 12-18 C of saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of Diglycerol ethers; saturated and unsaturated diglycerol ethers with a chain length of 8 to 24, especially 12 to 18, carbon atoms. and / or propylene glycol of unsaturated, branched and / or unbranched alkane carboxylic acids and saturated and unsaturated aryl esters with a chain length of 8 to 24, in particular 12 to 18, C atoms. Sorbitan esters of unsaturated, branched and / or unbranched alkane carboxylic acids .

[0161] Particularly advantageous W / O emulsifiers include glyceryl monostearate, monoisostearate, Glyceryl, Glyceryl Monomyristate, Glyceryl Monooleate, Monostearin Diglyceryl Monostearate, Diglyceryl Monoisostearate, Propylene Glycol Monostearate Cole, propylene glycol monoisostearate, propylene glycol monocaprylate , Propylene Glycol Monolaurate, Sorbitan Monoisostearate, Monolaurate Sorbitan monocaprylate, sorbitan monoisooleate, disodium Sucrose tearic acid, cetyl alcohol, stearyl alcohol, arachidyl alcohol Alcohol, behenyl alcohol, isobehenyl alcohol, selachyl alcohol, thymyl alcohol Polyethylene glycol (2) stearyl ether (steareth-2), monolaurate Glyceryl phosphate, glyceryl monocaprate and glyceryl monocaprylate. can be.

[0162] The compositions according to the invention also constitute perfume compositions for hair care and scalp care products. They can be used for minutes or as an additional itch relief, especially as they have a particular effectiveness. In particular, the composition may impart antiallergic properties to perfumed final products. A preferred perfume composition comprises: (a) a perceptually effective amount of perfume; and (b) an itch-modulating, anti-allergic agent. A synergistically effective combination of anthranilic acid amide and an antidandruff agent in an activating and / or desensitizing amount. and (c) optionally, one or more excipients and / or additives. At least one avenanthramide or its analogue, or at least one avenanthramide The composition containing the preparation containing venanthramide or its analogues has a characteristic weak odor. It has proven to be particularly advantageous that these are only odourless or even completely odourless. It is this property, among others, that has led to their use in aqueous compositions.

[0163] Other cosmetic and pharmaceutical agents which are particularly preferred for combination with the formulations according to the invention Regarding the excipients, carriers and auxiliaries which are acceptable for use in the preparation of pharmaceutical compositions, the relevant disclosures are incorporated herein by reference. In WO2007 / 062957 and WO2003 / 069994 Please refer to the detailed description.

[0164] The composition according to the present invention for delivering the active substance, i.e., avenanthramide, is a pharmaceutical composition comprising: Cosmetics or dermatological or keratin preparations, such as pump sprays, aerosol sprays, among others. sprays, creams, shampoos, ointments, tinctures, lotions, nail polish Easily absorbs care products (e.g. nail polish, nail polish remover, nail balsam) In this context, at least one avenanthramide or its derivatives can be incorporated. or preparations containing at least one avenanthramide or analog thereof. The cosmetic and / or dermatological or keratinogenic composition may contain, in the composition, an ingredient that is otherwise conventionally present. and may be present for cosmetic care or for dermatological or keratin treatment. In context it can be used to treat the skin, hair and / or nails.

[0165] If the cosmetic or pharmaceutical preparation is a solution or lotion, it can be used Solvents that can be used include: water or aqueous solutions; fatty oils, fats, waxes and other natural Natural and synthetic fatty acids, preferably esters of fatty acids with alcohols having low carbon numbers; For example, isopropanol, propylene glycol or glycerol, or aliphatic alcohols. Esters of alcohols with alkanoic acids having low carbon numbers or with fatty acids; Alcohols, diols or polyols having a high C number and their ethers are preferred. or ethanol, isopropanol, propylene glycol, glycerol, ethylene Glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol Cholesterol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl Monoethyl or monoethyl ether and similar products. Mixtures of the abovementioned solvents are particularly used. In the case of alcoholic solvents, water can be an additional constituent.

[0166] The cosmetic or pharmaceutical preparations may also be in a form suitable for topical application, for example, lotions, aqueous or as an aqueous-alcoholic gel, a vesicle dispersion, or a simple or complex emulsion. (O / W, W / O, O / W / O or W / O / W) liquid, semi-liquid or solid, e.g. For example, milk, cream, gel, cream-gel, paste or stick and optionally packaged as an aerosol; It may also take the form of a mousse or spray. Such preparations may be applied in the usual manner. It is prepared.

[0167] To prepare an emulsion, the oily phase can be advantageously selected from the following group of substances: Oils, mineral waxes; fatty oils, fats, waxes and other natural and synthetic fatty bodies, preferably Preferably, fatty acids and alcohols having low carbon numbers, such as isopropanol, propylene Esters with glycols or glycerol, or with fatty alcohols and low carbon numbers esters of alkanoic or fatty acids having the formula: alkyl benzoates; silicone oils; For example, dimethylpolysiloxane, diethylpolysiloxane, diphenylpolysiloxane and mixed forms thereof.

[0168] Advantageously, saturated and / or unsaturated, branched and / or unsaturated alkyl groups with a chain length of 3 to 30 C atoms. / or linear alkane carboxylic acids with a chain length of 3 to 30 C atoms, saturated and / or esters with unsaturated, branched and / or linear alcohols, aromatic carboxylic acids, Saturated and / or unsaturated, branched and / or straight, with a chain length of 3 to 30 C atoms Those from the group of esters with chain alcohols can be used. Preferred ester oils As isopropyl myristate, isopropyl palmitate, isopropyl stearate Pill, isopropyl oleate, n-butyl stearate, n-hexyl laurate, oleic acid n-Decyl leate, isooctyl stearate, isononyl stearate, isononyl Isononyl phosphate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-Hexyldecyl tearic acid, 2-octyldodecyl palmitate, oleic acid oleyl erucate, oleyl oleate, erucyl erucate and such esters and synthetic, semi-synthetic and natural mixtures of ethers, such as jojoba oil.

[0169] In addition, the oil phase may be any of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyds, and the like. The group may advantageously be selected from the group comprising saturated or unsaturated, branched or unbranched ethers. or unbranched alcohols, and also fatty acid triglycerides, specifically those with 8 to 24, and especially those with 12 Saturated and / or unsaturated, branched and / or unbranched with a chain length of ~18 C atoms Contains triglycerol esters of alkane carboxylic acids. Fatty acid triglycerides are synthetic , semi-synthetic and natural oils, such as olive oil, sunflower oil, soybean oil, peanut oil, natto oil, Advantageously selected from the group consisting of seed oil, almond oil, palm oil, coconut oil, palm kernel oil, etc. Any mixture of such oil and wax components may also be used to advantage. In some cases, a wax, e.g., pulp, may be used as the only lipid component of the oil phase. It is also advantageous to use cetyl methacrylate. Advantageously, the oil phase is 2-ethylhexyl Sostearate, Octyldodecanol, Isotridecyl Isononanoate, Isoeico San, 2-ethylhexyl coconut oil fatty acid, C12-15 alkyl benzoate, caprylic acid Selected from the group including capric triglyceride and dicaprylyl ether. ~15 Mixture of alkyl benzoate and 2-ethylhexyl isostearate, C12~15 Mixtures of alkyl benzoates and isotridecyl isononanoate and C12-15 benzoates Alkyl acetate, 2-ethylhexyl isostearate and isotridecyl isononanoate Particularly advantageous are mixtures of paraffin oil, squalane and squalene. The oil phase can also advantageously be used as a cyclic or linear silicone oil. It may contain or consist entirely of such oils, but may also contain other An oil phase component is preferably used in addition to silicone oil. Cyclomethicone (e.g., Decamethylcyclopentasiloxane can be advantageously used as a silicone oil. However, other silicone oils can also be used to advantage, including, for example, unsilicon oils. Decamethylcyclotrisiloxane, polydimethylsiloxane and poly(methylphenyl Siloxane) Cyclomethicone and isotridecyl isononanoate and cyclomethicone Mixtures of lomethicone and 2-ethylhexyl isostearate are also particularly advantageous.

[0170] The composition or cosmetic and / or pharmaceutical preparation according to the invention in the form of an emulsion The aqueous phase advantageously contains alcohols, diols or polyols having a low C number, as well as These ethers, preferably ethanol, isopropanol, propylene glycol, glycol Glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether propylene glycol monomethyl, monoethyl or monobutyl ether, diethyl Diethylene glycol monomethyl or monoethyl ether and similar products, with lower C Alcohols with a number of alcohols, such as ethanol, isopropanol, 1,2-propanediol, and glycerol, and in particular one or more thickening agents, The agents are advantageously in particular silicon dioxide, aluminum silicate, polysaccharides and their derivatives, e.g. For example, from the group containing hyaluronic acid, xanthan gum, and hydroxypropyl methylcellulose Of these, particularly advantageously, from the group comprising polyacrylates, preferably polyacrylates, i.e. Carbopol, e.g. types 980, 981, 1382, 2984 and 5984 One or more thickening agents, which may be advantageously selected from the group including carbopol, Each may be included by itself or in combination.

[0171] High concentrations of treatment substances are usually incorporated into cosmetic or pharmaceutical preparations for topical treatment of the skin. According to a preferred variant, the preparation comprises one or more animals and / or or vegetable processed fats and oils, e.g., olive oil, sunflower oil, refined soybean oil, parsley oil, oil, sesame oil, rapeseed oil, almond oil, borage oil, evening primrose oil, coconut oil, shea oil Butter, jojoba oil, sperm whale oil, beef tallow, beef foot oil and lard, and optionally others The treatment components include, for example, C8 to C30 fatty alcohols. The fatty alcohols may be saturated or unsaturated and straight-chain or branched. Examples include decanol, decenol, octanol, octenol, dodecanol, and dodecanol. Decadienol, octadienol, decadienol, dodecadienol, oleyl alcohol Alcohol, ricinoleyl alcohol, erucic alcohol, stearyl alcohol, isostearyl Alcohol, cetyl alcohol, lauryl alcohol, myristyl alcohol, arachidonic acid Diethyl alcohol, Caprylic alcohol, Capric alcohol, Linoleyl alcohol, Linolenyl alcohol and behenyl alcohol, as well as these Guerbet alcohols This list may be expanded, if desired, to include other compounds that are structurally and chemically related. The fatty alcohol may be expanded to include ethanol. The fatty alcohol is preferably a naturally occurring fatty acid. They arise from fatty acids and are usually prepared by reduction from the corresponding esters of fatty acids. and fatty alcohol fractions formed by reduction from fatty oils, e.g. beef tallow, peanut Oil, rapeseed oil, cottonseed oil, soybean oil, sunflower oil, palm kernel oil, linseed oil, corn oil Castor oil, rapeseed oil, sesame oil, cocoa butter and cocoa fat can also be used. Cut.

[0172] Treatment substances which can be preferably combined with the cosmetic or pharmaceutical preparations according to the invention Examples of glycerols that may be used include: ceramides, N-acylsphingosines, These lipids are either known to be fatty acids (fatty acid amides of sphingosine) or synthetic analogues of such lipids (e.g. so-called pseudo-ceramides), which significantly improve the water-retaining capacity of the stratum corneum; phospholipids , such as soy lecithin, egg lecithin and cephalin; Vaseline, paraffin and silicone oils, the latter being, inter alia, dialkyl- and alkylaryl-siloxanes, For example, dimethylpolysiloxane and methylphenylpolysiloxane, Includes alkoxylated and quaternized derivatives of.

[0173] Hydrolyzed animal and / or vegetable proteins may also be included in the composition according to the invention. These can be advantageously added to cosmetic or pharmaceutical preparations in which they are used. Advantageous examples in this connection are: Especially elastin, collagen, keratin, milk protein, soy protein, oenocyte protein Proteins, pea proteins, almond proteins and wheat protein fractions or corresponding Hydrolyzed proteins that are capable of producing fatty acids, as well as their condensation products with fatty acids, and further quaternized hydrolyzed proteins. Examples of suitable proteins include vegetable proteins, and the use of hydrolyzed vegetable proteins is preferred.

[0174] The cosmetic or pharmaceutical preparation may also comprise a cosmetically or pharma- ceutical acceptable carrier, e.g. Examples include, but are not limited to, one of the following commonly used in the art: (not specified): lactose, glucose, sucrose, sorbitol, mannitol, denaturant Pu, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, Microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, Magnesium tearate, mineral oil, etc. Cosmetics or pharmaceutical preparations may also contain additives in addition to the above components. In addition, the composition may contain lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharma- ceutically acceptable carriers and formulations can be found in Remington's Pharmaceuticals, Inc. The results are described in detail in Aceutical Sciences (19th ed., 1995). .

[0175] For use, compositions or cosmetic or pharmaceutical preparations, i.e. dermatological or keratinological preparations is applied in a sufficient amount and in a manner customary in cosmetics or pharmaceuticals to the skin, scalp, Applied to hair and / or nails.

[0176] Finally, the present invention relates to a method for preparing a composition according to the invention, comprising the steps of: - providing at least one avenanthramide or analog thereof; and To - adding at least one penetration enhancer to said avenanthramide or analogue thereof; and mixing The present invention relates to a method comprising the steps of:

[0177] The composition thus obtained can be added to a final, i.e. conventional, preparation or formulation. Cut.

[0178] Alternatively, the individual components of the composition according to the invention can be added separately to the final formulation. Cut.

[0179] Although the present invention has been specifically shown and described with reference to preferred embodiments, and various changes in form and detail may be made without departing from the scope of the present invention. Moreover, the present invention is intended to cover all possible variations thereof. Unless specifically indicated otherwise, any combination of the above-described elements may be used. Includes.

[0180] In addition, while features or aspects of the invention are described in terms of Markush groups, those of skill in the art will appreciate that The present invention also relates to any individual member or subgroup of members of the Markush group. I am aware of what is stated here in this regard.

[0181] The present invention will now be described in detail with reference to the following examples, which are merely illustrative of the present invention. The invention is not limited by or to the following examples, which are merely illustrative of the invention. This is not to be the case. EXAMPLES

[0182] The avenanthramide (Avn) used in the examples can be synthesized by known processes, e.g. It was synthesized according to known processes detailed in O2004 / 047833.

[0183] For more accurate quantitative analysis only, the concentrations of avenanthramide used in the following examples are From the concentration of avenathramide in the composition according to the present invention, expensive.

[0184] Example 1: Investigation of the permeation behavior of Avn A

[0185] Using the Skin PAMPA™ (Parallel Artificial Membrane Permeability Assay) model, From the commercial formulation, the permeability of Avn A across an artificial membrane mimicking the stratum corneum was evaluated.

[0186] As the main permeability barrier of the skin, the stratum corneum (SC) is composed of keratinocytes embedded in extracellular lipids. The lipid mixture of the Skin PAMPA™ membrane is composed of a similar amount of vesicles as the SC. Certramide (a synthetic ceramide analogue), stearic acid and co Skin PAMPA™ sandwiches consist of two 96 well sandwiches. One plate contains a filter impregnated with porous lipids. The wells of the lower plate are filled with the formulation. The wells of the upper plate were filled with receptor solution. The plates were then stacked and Semi-solid formulations were evaluated using the Skin PAMPA™ model. and was found to correlate well with ex vivo permeability tests. It has also been found that the (trademark) system is advantageously compatible with emulsions containing non-ionic surfactants. It has been proven. [Table 2]

[0187] Generation method: Heat phases A and B separately to 70°C; Disperse phase C in phase B; Disperse phase BC into phase A. Add and emulsify using an ULTRA TURRAX® stir bar (2 minutes); Allow to cool using a bladed stir bar; add Phase D for neutralization. Formulations are prepared in bulk. The active substances were pre-dissolved in the corresponding excipients and added to the formulation (15 min with a bladed stir bar). Stir for a while.

[0188] Alternatively, the corresponding avenanthramides were dissolved in glycerin or ethanol or a mixture of these. It is also possible to predissolve the diol in the aqueous phase of the emulsion and add the corresponding diol to the aqueous phase of the emulsion. This leads to the same result as the previous embedding method.

[0189] Receptor solution: Dissolve 180 ml of buffer in 20 ml ethanol (buffer: 20 mmol / l citric acid, pH 5.5) mixed with; 0.84 g of anhydrous citric acid was dissolved in approximately 180 g of water; The pH was adjusted to 5.5 using 30% sodium hydroxide solution; Following pH adjustment, the solution was filled to 200 g with water.

[0190] Sample preparation: After 240 minutes, approximately 180 μl of each Skin PAMPA™ sample was analyzed by HPLC. Transferred to a small vial.

[0191] Conditions for HPLC analysis: Instrument: Agilent HP1100, connected to Waters Empower3SR3 Column: Waters XBridge® C18, 3.5 μm, 3.0×50 mm Column temperature: 30℃ Mobile phase A: Water + 0.1% formic acid Mobile phase B: Methanol Flow rate: 1.02ml / min Injection volume: 25μl Wavelength: 304nm Gradient table: Time [min] % of A % of B Default 65.0 35.0 6.00 50.0 50.0 6.05 65.0 35.0 8.00 65.0 35.0

[0192] The results are summarized in the table below.

[0193] [Table 3]

[0194] The results clearly show that the addition of 1,2-diols strongly increases the permeability of Avn A. Modulation by Hydrolite-5 (1,2-pentanediol) The increase was concentration-dependent, with a 19% increase at the 3% dose and a 59% increase at the 5% dose. Hydrolite-6 (1,2-hexanediol) was used to increase the permeability of Avn A. was enhanced by 46% at the 2% dose, which was comparable to the 19% enhancement achieved by Hydrolite-5 at the 3% dose. Compared to the improvements, it was even more efficient than Hydrolite-5.

[0195] 1,2-alkanediols possess skin moisturizing properties, and itchy skin is often dry. The goal is to reduce itching, as it involves dry, sensitive, or damaged skin. This provides additional benefit to skin and scalp care formulations.

[0196] They also impart a light and sophisticated skin feel to the formulation, which It will be much more acceptable to users.

[0197] Example 2: Investigation of the permeation behavior of Avn L

[0198] Using the Skin PAMPA™ (Parallel Artificial Membrane Permeability Assay) model, The permeability of Avn L across an artificial membrane mimicking the stratum corneum was evaluated from the commercial preparations described above. It was evaluated as follows.

[0199] [Table 4]

[0200] The results are summarized in the table below.

[0201] [Table 5]

[0202] The results clearly showed that the addition of 1,2-diols strongly increased the permeability of Avn L. Hydrolite-5 (1,2-pentanediol) at a 3% dose Modulation by Hydrolite at a 1% dose resulted in a 125% increase. 6 (1,2-hexanediol) enhanced Avn L permeability by 160%, so 3% It was more effective than Hydrolite-5 at doses.

[0203] Example 3: Investigation of the permeation behavior of Avn B

[0204] Using the Skin PAMPA™ (Parallel Artificial Membrane Permeability Assay) model, The permeability of Avn B across an artificial membrane mimicking the stratum corneum was evaluated from a commercial preparation as described above. It was evaluated as follows.

[0205] Unlike Examples 1 and 2, this time, the HPL of each Skin PAMPA™ sample was Receptor solution samples for C analysis were taken exactly 120 min later.

[0206] [Table 6]

[0207] The results are summarized in the table below.

[0208] [Table 7]

[0209] The results clearly show that the addition of 1,2-diols strongly increases Avn B permeability. Modulation by Hydrolite-6 (1,2-hexanediol) The increase was concentration-dependent, with a 62% increase at the 1% dose and a 76% increase at the 2% dose. It was.

[0210] SymDiol68, 1,2-Hexanediol (Hydrolite-6) and 1,2 A 1:1 mixture of 1:1 octanediol (Hydrolite-8) and 1:1 octanediol (Hydrolite-8) reduced the permeability of Avn B. Hydrolite-6 alone at the same dose enhanced the inflammatory response by 87% compared with 62%. It was more effective at a 1% dose than

[0211] SymDiol 68 also enhances preservatives in formulations, allowing formulations to contain lower levels of preservatives. Itching is associated with dry, sensitive, or damaged skin. This is especially true for the itching that is often soothed by applying Avn. Beneficial for firm skin.

[0212] Example 4: Dihydroavenanthramide in the absence of penetration enhancers Avn A, Avn B, Av compared to antramide)D(DhAvn D) Comparison of permeation behavior of Avn L and Avn C over time (per ml of receptor liquid) (μg) of Avns or DhAvnD

[0213] Using the Skin PAMPA™ (Parallel Artificial Membrane Permeability Assay) model, From the product formulation, Avn A, Avn B, Avn C and Avn D crossed the artificial membrane mimicking the stratum corneum. The skin permeability of Avn and Avn L was compared with that of dihydroavenanthramide D (DhAvnD). and evaluated as described above. [Table 8]

[0214] Generation method: Heat phases A and B separately to 70°C; Disperse phase C in phase B; Disperse phase BC into phase A. Add and emulsify using an ULTRA TURRAX® stir bar (2 minutes); Allow to cool using a bladed stir bar; add Phase D for neutralization. Formulations are prepared in bulk. The active substance was pre-dissolved in glycerin or water or a mixture of these and added to the formulation. The mixture was stirred with a bladed stirring rod for 15 minutes.

[0215] Sample preparation: After 60, 120 and 240 minutes, approximately 180 μl of each Skin PAMPA™ The samples were transferred to HPLC micro-vials and analyzed by HPLC.

[0216] The results are summarized in Table 9 below.

[0217] [Table 9]

[0218] The results are summarized in Figure 1. As is apparent from Figure 1, Avn A, Avn B, A vn L has a penetration behavior of Avn A < Avn B < Avn L and is weaker than DhAvn D. However, Avn C penetrates better than DhAvn D.

[0219] Example 5: Modulation of the penetration behavior of Avn L compared to dihydroavenanthramide D (DhAvn D) (3% by weight) in the presence of 1,2 - pentanediol (Hydrolite5) The permeability of Avn L across an artificial membrane mimicking the stratum corneum from a cosmetic formulation in the presence of 3% 1,2 - pentanediol was evaluated as described above, compared to dihydroavenanthramide D (DhAvn D).

[0220] Using the Skin PAMPA (trademark) (Parallel Artificial Membrane Permeability Assay) model, in the presence of 3% 1,2 - pentanediol, the permeability of Avn L across an artificial membrane mimicking the stratum corneum from a cosmetic formulation was compared to dihydroavenanthramide D (DhAvn D) and evaluated as described above. As described above.

[0221]

Table 10

[0222] The results are summarized in Table 11 below.

[0223]

Table 11

[0224] The addition of 1,2 - pentanediol (Hydrolite 5) to dihydroavenanthramide D results in a 57% enhancement of permeability after 240 minutes. The addition of 1,2 - pentanediol (Hydrolite 5) to avenanthramide L results in a 12 5% enhancement of permeability.

[0225] Example 6: Formulation examples

[0226] [Table 12-1] [Table 12-2]

[0227] [Table 13]

[0228] [Table 14]

[0229] [Table 15]

[0230] [Table 16]

[0231] The perfume oils PO1, PO2, PO3, PO4, or PO5 are prepared separately in each case. The preparation presented below was obtained.

[0232] Cosmetic preparations / formulations (amounts in % by weight of total preparations / formulations)

[0233] [Table 17]

[0234] [Table 18]

[0235]

Table 19-1

Table 19-2

[0236]

Table 20-1

Table 20-2

[0237]

Table 21

[0238]

Table 22

[0239]

Table 23

[0240]

Table 24-1

Table 24-2

[0241]

Table 25-1

Table 25-2

[0242]

Table 26-1

Table 26-2

[0243]

Table 27-1

Table 27-2

[0244]

Table 28-1

Table 28-2

[0245]

Table 29-1

Table 29-2

[0246]

Table 30

[0247]

Table 31

[0248]

Table 32

[0249]

Table 33

[0250]

Table 34

[0251]

Table 35

[0252]

Table 36

[0253]

Table 37

[0254]

Table 38

[0255]

Table 39

[0256]

Table 40

[0257]

Table 41

[0258]

Table 42

[0259]

Table 43

[0260]

Table 44

[0261]

Table 45

[0262]

Table 46

[0263]

Table 47

[0264]

Table 48

[0265]

Table 49

[0266]

Table 50

[0267]

Table 51

[0268]

Table 52

[0269]

Table 53

[0270]

Table 54

[0271]

Table 55-1

Table 55-2

[0272]

Table 56-1

Table 56-2

[0273]

Table 57

[0274]

Table 58

[0275]

Table 59

[0276]

Table 60

[0277]

Table 61

[0278]

Table 62

[0279]

Table 63

[0280]

Table 64

[0281]

Table 65

[0282]

Table 66

[0283]

Table 67

[0284]

Table 68-1

Table 68-2

Table 68-3

Table 68-4

Table 68-5

Table 68-6

Claims

1. at least one avenanthramide selected from the group consisting of avenanthramides A, B, C, D, E, F, G, H, L and mixtures of these avenanthramides, at least one penetration enhancer which is a linear alkanediol having 3 to 12 C atoms; A composition comprising or consisting of:

2. 2. The composition of claim 1, wherein the at least one avenanthramide is obtained from an oat source of the oat species Avena sativa or Avena nuda.

3. 3. The composition of claim 1 or 2, wherein the penetration enhancer is selected from the group consisting of 1,2-propanediol, 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol, 1,2-nonanediol, 1,2-decanediol or 1,2-dodecanediol, 1,3-butanediol (butylene glycol), 1,3-propanediol, 1,4-butanediol, and any mixture thereof.

4. Based on the total weight of the composition, - 0.0001 to 5.0% by weight of at least one avenanthramide; and - 0.01 to 10.0% by weight of at least one penetration enhancer The composition of any one of claims 1 to 3, comprising:

5. 5. Non-therapeutic and cosmetic uses of a composition according to any one of claims 1 to 4 in skin protection and skin care, scalp protection and care, hair care, nail care or in the prevention and / or treatment of skin conditions, intolerant or sensitive skin, skin irritation, skin redness, wheals, pruritus (itching), skin aging, wrinkle formation, loss of skin volume, loss of skin elasticity, pigment spots, pigmentation disorders, dry skin and dry skin for skin moisturisation.

6. A composition according to any one of claims 1 to 4 for use as a medicament.

7. 7. The composition according to claim 6 for use in the prevention and / or treatment of skin or keratinous diseases having a barrier-related, inflammatory, immunoallergic, atherogenic or hyperproliferative component, and / or in the prevention and / or treatment of skin diseases associated with increased ROS production.

8. 8. The use according to claim 7, wherein the skin or keratinous disease is selected from the group consisting of atopic dermatitis (neurodermatitis), psoriasis, acneiform eruptions, asteatosis, xerosis, eczema, hyper- and hyposeborrhea, dermatitis, rosacea, erythema, pruritus, inflammation, irritation, fibrosis, lichen planus, pityriasis rosea, tinea versicolor, autoimmune blistering diseases, urticaria, angioedema, allergic skin reactions, wound healing, and tissue regeneration.

9. 5. Use of a composition according to any one of claims 1 to 4 for preparing a cosmetic or pharmaceutical preparation, a dermatological or keratinological preparation.

10. A cosmetic or pharmaceutical preparation comprising a composition according to any one of claims 1 to 4.

11. 11. The cosmetic or pharmaceutical preparation according to claim 10, further comprising one or more active substances selected from the group consisting of skin moisturising and / or water retaining substances, cooling agents, osmolytes, keratinising substances, nutritional substances, anti-inflammatory, antibacterial or antifungal substances, substances with redness relieving or itching relieving action, analgesic substances, and any mixtures thereof; and / or cosmetically or pharma- ceutically acceptable excipients selected from the group consisting of antioxidants, preservatives, (metal) chelating agents, surface active substances, emulsifiers, perfume oils, defoamers, colouring agents, pigments with colouring action, thickeners, plasticisers, fats, oils, waxes or other conventional constituents of cosmetic formulations, alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives, and any mixtures thereof.

12. 12. A cosmetic or pharmaceutical preparation according to claim 10 or 11, provided as a solution, tincture, lotion, gel, cream, ointment, spray or shampoo.

13. A method for preparing a composition according to any one of claims 1 to 4, comprising the steps of: - providing at least one avenanthramide selected from the group consisting of avenanthramides A, B, C, D, E, F, G, H, L and mixtures of these avenanthramides; and - adding and mixing at least one penetration enhancer, which is a linear alkanediol having 3 to 12 C atoms, with said avenanthramide. A method comprising:

Images