US00891. 1795B2

(12) United States Patent (10) Patent No.: US 8,911,795 B2 Schmaus et al. (45) Date of Patent: *Dec. 16, 2014

(54) COMPOSITIONS COMPRISING (52) U.S. Cl. DHYDROAVENANTHRAMIDED AND CPC ...... A61O5/006 (2013.01); A61 K 2800/75 CLIMBAZOLEAS COSMETIC AND (2013.01); A61 K31/196 (2013.01); A61 K PHARMACEUTICAL COMPOSITIONS FOR 8/445 (2013.01); A61O 19/00 (2013.01) ALLEVIATING ITCHING USPC ...... 424/640; 514/188: 514/345; 514/563 (58) Field of Classification Search (75) Inventors: Gerhard Schmaus, Höxter (DE); None Joachim Röding, Badenweiler (DE) See application file for complete search history. (73) Assignee: Symrise AG, Holzminden (DE) (56) References Cited U.S. PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 4,070,484 A 1/1978 Harita et al. 8,409,552 B2 * 4/2013 Schmaus et al...... 424,61 U.S.C. 154(b) by 1390 days. 2003/0161802 A1* 8, 2003 Flammer et al...... 424.70.1 This patent is Subject to a terminal dis 2003/0228272 Al 12/2003 Amjad et al. claimer. 2006/0089413 A1* 4/2006 Schmaus et al...... 514,563 (21) Appl. No.: 12/095,453 FOREIGN PATENT DOCUMENTS JP 2005187398 7/2005 (22) PCT Filed: Nov. 3, 2006 WO WO-2004O35O15 4/2004 WO WO 2004/047833 * 6, 2004 ...... A61K 31,196 (86). PCT No.: PCT/EP2006/068077 WO WO-2004O47833 6, 2004 WO WO-2006134013 12/2006 S371 (c)(1), WO WO-2006134120 12/2006 (2), (4) Date: Apr. 23, 2009 OTHER PUBLICATIONS (87) PCT Pub. No.: WO2007/062957 Wilbrand, G., “Dealing with Dandruff.” Soap Perfumery and Cos PCT Pub. Date: Jun. 7, 2007 metics, United Trade Press Ltd. London, GB, vol. 72, No. 4, 1999, pp. 79-83, XP009082627, ISSN: 0037-749X, Abstract. (65) Prior Publication Data Wilbrand G., “Vergleichsstudie Ichthyol Pale Versus Zink Pyrithion (Bei Kopfschuppen, Juckreiz, Fettigem Haar). Kosmetische US 2009/0226,537 A1 Sep. 10, 2009 Medizin, Grosse Verlag GMBH, Berlin, DE, vol. 20, No. 5, Nov. 1999, pp. 252-253, XP009082589, ISSN: 1430-4031, Abstract. Related U.S. Application Data * cited by examiner (60) Provisional application No. 60/740,690, filed on Nov. Primary Examiner — Carlos Azpuru 30, 2005. Assistant Examiner — David Browe (74) Attorney, Agent, or Firm — Dilworth & Barrese, LLP (51) Int. Cl. (57) ABSTRACT AOIN 59/6 (2006.01) Compositions comprising dihydroavenanthramide D and A6 IK33/32 (2006.01) climbazole; and, cosmetics or pharmaceutical end products A61O5/00 (2006.01) comprising the compositions, useful for treating skin and/or A6 IK3I/96 (2006.01) hair. A6 IK 8/44 (2006.01) A61O 19/00 (2006.01) 13 Claims, No Drawings US 8,911,795 B2 1. 2 COMPOSITIONS COMPRISING This object is achieved according to the invention by the DHYDROAVENANTHRAMIDED AND provision of a mixture comprising or consisting of CLIMBAZOLE AS COSMETIC AND (a) one or more compounds of Formula 1: PHARMACEUTICAL COMPOSITIONS FOR ALLEVIATING ITCHING Yp CROSS REFERENCE TO RELATED RI O 21 A. APPLICATIONS 10 N N N X.-- H The application claims the benefit of PCT/EP2006/068077 in 2 R2 COOR3 filed on Nov. 3, 2006, and of U.S. Provisional Patent Appli cation 60/740,690 filed on Nov.30, 2005, the disclosures of which are hereby incorporated by reference. where the symbols in the compound or each compound of 15 Formula 1 are defined as follows: m=0, 1, 2 or 3, BACKGROUND OF THE INVENTION p=0, 1 or 2. n=0, 1 or 2, The present invention relates to mixtures of anthranilic where, when n=1 or 2, R' and R in pairs are each H or acid amides and antidandruff agents which can be used espe together are another chemical bond (e.g. in cinnamic acid cially as cosmetic and pharmaceutical compositions for alle derivatives), where, when m=1, 2 or 3, each X independently of the others viating itching. is OH, Oalkyl or Oacyl, WO 2004/047833, on which the present invention is based, and where, when p=1 or 2, each Y independently of the others discloses that certain anthranilic acid amides (of Formula 1) 25 is OH, Oalkyl or Oacyl, and inhibit the substance P-induced release of histamines from R=H or alkyl (especially CHs, linear or branched alkyl mast cells and thus are suitable as cosmetic and pharmaceu chains having 2 to 30 C atoms), R=H also representing the tical compositions for alleviating itching. The compounds of corresponding cosmetically or pharmaceutically acceptable Formula 1 indicated in WO 2004/047833 are also particularly 30 salts and Solvates; preferred for use within the framework of the present inven and tion. (b) one or more antidandruff agents. WO 2004/047833 discloses that the use concentration of a DETAILED DESCRIPTION OF THE INVENTION particular compound of Formula 1 is up to 10 percent by weight, based on the total weight of a ready-to-use cosmetic 35 Formula 1 above thus coversall the compounds of Formula or pharmaceutical end product. In some cases, however, Such 1 from WO 2004/047833 as well as some compounds not high use concentrations seem to be problematic for cosmetic covered by the disclosure of WO 2004/047833. and/or pharmaceutical reasons relating e.g. to formulation Although it is already known from WO 2004/047833 that a technology. cosmetic preparation can contain, in addition to a compound 40 of Formula 1 (with the somewhat narrower definition accord ing to WO 2004/047833), other active compounds for allevi BRIEF SUMMARY OF THE INVENTION ating reddening and itching, WO 2004/047833 does not dis close that the addition of antidandruff agents leads to a synergistic intensification of the action of a compound of The object of the present invention was therefore to provide 45 Formula 1 (with the somewhat broader definition according mixtures active in the alleviation of itching and/or the reduc to the present invention). tion of skin reddening which contain, in addition to one or Although it is known that certain antidandruff agents can more compounds of Formula 1: reduce susceptibility to itching and thereby exert an alleviat ing effect (G. Wilbrand, Kosmetische Medizin Vol.20(5), pp 50 252-253, 1999), there are no disclosures relating to the com 1 bination of antidandruff agents with compounds of Formula Yp 1. Likewise, there are no disclosures relating to the synergis tic interaction of antidandruff agents with compounds of For RI O 1 mula 1. N N N 55 Particularly preferred compounds of Formula 1 for use in X.-- H the mixture according to the invention are those in which: in 21 R2 COOR3 n=1 or 2 and the sum p+m-0 and/or p+m-0 and X or Y is selected at least once from the group 60 comprising OH and Oacyl. It is particularly preferable to use a compound of Formula (see below for definitions of substituents and variables), 1 in which: another compound which interacts synergistically with the n=1 compound(s) of Formula 1 so that even low use concentra and tions of the compound(s) of Formula 1 and the other com 65 p+m22. pound are sufficient to produce a good effect in the alleviation with the proviso that X and Y together are selected at least of itching or the reduction of reddening. twice from the group comprising OH and Oacyl. US 8,911,795 B2 3 4 It is also preferable to use a compound of Formula 1 in -continued which: n=1, and also: m=1, 2 or 3, with the proviso that X is selected at least once from the group comprising OH and Oacyl, and/or 10 p=1 or 2, with the proviso that Y is selected at least once from the group MeO comprising OH and Oacyl. If n has the value 1, R' and R are each preferably H, 15 although it is also possible for R' and R together to be another chemical bond. 10 The compound of Formula 1 is preferably selected from the group comprising:

11 HO 25 OH

-CCO2H HO OH 30 OCO2H

12 HO OH

OCO2H 35 HO N OH

13 MeO 40 OH

CO2H MeO H

OH 45 MeO

30 CO2H OH HO 50

OH N CO2H 55

CO2H 31 HO

OH 60

MeO

-OCO2H 65 CO2H HO MeO

US 8,911,795 B2 7 8 -continued -continued OH O H

N HO O1nS1an C 2 H 51 OH 10 a- 59 OO YO1OYnS)ann)an Y O H

NN 15 HO CC 22 HH N OYYXaYa Ya 52 HHOO OO C H HHS O H 2 60 2O

HO OH1s-1S-1N 25 OH1s-1S-1N 53 61 O H O OYYOYYSYNYYY1Ye Y

30 N Y YX a Ya Y Y,O Oalax a N H CC HH 22 62 O H HO O H O 54 35 N HO CO 2 H N H1s-1S-1NO 40 63 O H O 55 N HO 45 CO 2 N OYXa H 64 O H

50 O 56 OH N HO S.CO 55 N 65 O H

57 60 OH Y YX Y. Y. Y. Y.O N OYYSYYa Y C 2 H HO OH N 65 The above illustrations relate essentially to compounds of OOOOO22222 Formula 1 in which n=1. US 8,911,795 B2 9 10 However, the use of compounds of Formula 1 in which n=0 -continued is also frequently preferred, in which case the following defi 27 nition preferably applies: m+p22. with the proviso that at least two of the substituents X and Y are selected from the group comprising OH and Oacyl. It is particularly preferable to use compounds of Formula 1 (where n=0) selected from the group comprising: 28 10 O

HO N H CO2H 15 HO 29 N O CO2H HO N 21 H OH CO2H OH 34 OH

25 CO2H O HO 22 N H HO 30 CO2H HO OH N H 35 CO2H OH HO O OH 35 23 N H O CO2H OH N 40 66 H |C OH CO2H MeO O 24 HO O N 45 H CO2H HO

OH HO 67 50 OH 25 c O MeO HO N 55 H CO2H H CO2H HO

OH 26 68 60 OH O

HO N H CO2H 65 CO2H HO OH HO US 8,911,795 B2 11 -continued -continued 69 77 OH OH

O O

HO HO N N H H CO2H CO2H HO 10 78 70 OH OH O

N N 15 H O H O CO2H OH HO O OH CO2H 79 71 OH OH O

N H N HO H O CO2H CO2H 8O MeO 25 OH 72 OH O

30 N HO H N H C. CO2H CO2H MeO 73 35 In the compounds described as particularly preferred and OH indicated by their structural formulae, R is always H. In place of these preferred compounds, it is also preferable MeO in each case to use the corresponding compounds in which N H R=CH or linear or branched alkyl having 2 to 30 Catoms. CO2H 40 Preferred individual antidandruff agents for use within the HO framework of the present invention are listed below. 74 Preferred antidandruff agents are climbazole and other OH azoles, e.g. benzimidazole, benzothiazole, bifonazole, buta conazole nitrate, clotrimazole, croconazole, eberconazole, 45 econazole, elubiol, fenticonazole, fluconazole, flutimazole, isoconazole, ketoconazole, lanoconazole, metronidazole, MeO N miconazole, neticonazole, omoconazole, oxiconazole nitrate, H Sertaconazole, Sulconazole nitrate, thioconazole, diazoles CO2H and triazoles, e.g. terconazole and itraconazole, and any HO 50 desired combinations of Saidazoles. 75 Other antidandruffagents which can be used are pyrithione OH salts, especially 1-hydroxy-2-pyrithione salts, preferred pyrithione salts being those of the metal cations of Sodium, Zinc, tin, calcium, magnesium, aluminum and Zirconium. The 55 Zinc salt of 1-hydroxy-2-pyrithione (known as "Zinc N pyrithione” or “ZPT) is particularly preferred. H Otherantidandruff agents include coal tar, Sulfur, selenium CO2H sulfides, aluminum chloride, octopirox (INCI: Piroctone Ola HO mine), cyclopiroXolamines, undecylenic acid and its metal 76 60 salts, potassium permanganate, Sodium thiosulfate, propy OH lene glycol, other branched and unbranched aliphatic diols O and polyols (e.g. 1,2-diols having 5-18 carbon atoms), urea HO preparations, griseofulvin, 8-hydroxyquinoline, ciloquinol, N H thiobendazole, thiocarbamates, triclosan, haloprogin, poly 65 enes, hydroxypyridone, morpholine, benzylamine, ally CO2H lamines (e.g. terbinafine), tea tree oil, clove oil, coriander oil, palmarosa oil, thyme oil and cinnamon oil, as well as ethereal US 8,911,795 B2 13 14 oil of bitter orange, cinnamaldehyde, citronellic acid, farne especially climbazole and otherazoles, pyrithione salts, par sol, berberine, hinokitiol, tropolone, birch tar oils, ichthyol ticularly Zinc pyrithione, ichthyol and octopirox, ranges from (sulfonated shale oil), Sensiva SC-50 (ethylhexyl glycerol), 1:100 to 2:1, preferably from 1:50 to 1:1 and particularly polyglycerol esters, e.g. polyglycerol-3 caprylate, arylalkyl preferably from 1:10 to 1:2. alcohols, e.g. phenylethyl alcohol, 3-phenyl-1-propanol, 5 The mixtures according to the invention can be combined vetikol (4-methyl-4-phenyl-2-pentanol), muguet alcohol with a large number of other components to give preferred (2,2-dimethyl-3-phenylpropanol), Elestab HP-100, azelaic cosmetic and/or pharmaceutical mixtures or products. acid, lyticase, isothiazalinones, e.g. octylisothiazalinone, Combination with Skin Moisture Regulators: iodopropynyl butyl carbamate (IPBC) and combinations of Itching occurs with particular intensity especially when the these active compounds. 10 skin is dry. The use of skin moisture regulators in cosmetic Those skilled in the art can extend the following list with and pharmaceutical products can significantly alleviate itch many otherantidandruff agents; the antidandruff agents listed ing. The synergistically effective combinations according to can also be used in combination with one another: the invention of compounds of Formula 1 (anthranilic acid Antidandruff agents which are preferred on the basis of amides) and antidandruff agents can therefore also be com their particular synergistic effect are climbazole, Zinc 15 bined particularly advantageously with skin moisture regula pyrithione, ichthyol and octopirox (INCI: Piroctone Ola tors. Cosmetic preparations containing a mixture according mine). to the invention can therefore advantageously also contain the A very particularly preferred antidandruff agent is climba following moisture retention regulators: sodium lactate, urea, Zole (trade name: Crinipan). urea derivatives, alcohols, glycerol, diols such as propylene The mixtures according to the invention, especially those glycol, hexylene glycol, 1.2-pentanediol. 1.2-hexanediol. characterized as preferred, possess a synergistically intensi 1.2-heptanediol. 1.2-octanediol. 1.2-nonanediol. 1.2-de fied efficacy againstitching. The efficacy of mixtures accord canediol or mixtures of said diols, especially mixtures of ing to the invention is Surprisingly Superior to that of products 1.2-hexanediol and 1.2-octanediol, collagen, elastin or hyalu exclusively comprising one or more compounds of Formula 1 ronic acid, diacyl adipates, petrolatum, urocanic acid, leci (as indicated above) or exclusively comprising one antidan 25 thin, panthenol, phytantriol, lycopene, (pseudo-)ceramides, druff agent. glycosphingolipids, cholesterol, phytosterols, chitosan, The mixtures according to the invention are particularly chondroitin Sulfate, lanolin, lanolin esters, amino acids, effective and furthermore are free of any toxicologically or alpha-hydroxy acids (e.g. citric acid, lactic acid, malic acid) dermatologically critical secondary components; they can and derivatives thereof, mono-, di- and oligosaccharides Such therefore be used without problems in pharmaceutical or 30 as glucose, galactose, fructose, mannose, fructose and lac cosmetic products. In general, it is pointed out that, in the tose, poly Sugars such as B-glucans, especially 1,3-1,4-3-glu concentration range relevant to efficacy, the substances to be can from oats, alpha-hydroxy fatty acids, triterpene acids used in cosmetic and/or pharmaceutical products Such as betulinic acid or ursolic acid, and algae extracts. should be toxicologically safe, Depending on the Substance, the use concentration of the should have a good skin tolerability, 35 moisture retention regulators ranges from 0.1 to 10% (m/m) should be stable (especially in the conventional cosmetic and preferably from 0.5 to 5% (m/m), based on the total and/or pharmaceutical formulations), weight of a ready-to-use cosmetic or pharmaceutical end should preferably be odorless and product. These data apply especially to diols that are advan should be inexpensive to prepare (i.e. by using standard tageously to be used, such as hexylene glycol. 1.2-pen processes and/or by starting from standard precursors). 40 tanediol. 1.2-hexanediol. 1.2-octanediol and 1,2-decanediol. These requirements are met by the mixtures according to as well as mixtures of 1.2-hexanediol and 1.2-octanediol. the invention. Combination with Cooling Agents: Although the use concentration of the compounds of For The use of cooling agents in cosmetic and pharmaceutical mula 1 to be used according to the invention can range from products can alleviate itching. The synergistically effective 0.0001 to 10 percent by weight—depending on the sub 45 combinations according to the invention of compounds of stance—as is already the case according to WO 2004/047833, Formula 1 (anthranilic acid amides) and antidandruff agents it is preferable to use a low concentration of the compound(s) can therefore additionally be combined particularly advanta of Formula 1. A concentration range of 0.001 to 1 percent by geously with cooling agents. Preferred individual cooling weight is particularly preferred and a range of 0.01 to 0.2 agents for use within the framework of the present invention percent by weight is very particularly preferred, based in each 50 are listed below. Those skilled in the art can add a large case on the total weight of a ready-to-use cosmetic or phar number of other cooling agents to this list; the cooling agents maceutical end product. listed can also be used in combination with one another: Depending on the Substance, the use concentration of the 1-menthol, d-menthol, racemic menthol, menthone glycerol antidandruff agents to be used according to the invention acetal (trade name: Frescolater MGA), menthyl lactate (trade ranges preferably from 0.01 to 20 percent by weight and 55 name: FrescolatR ML; menthyl lactate is preferably 1-men particularly preferably from 0.1 to 5 percent by weight, based thyl lactate, especially 1-menthyll-lactate), Substituted men on the total weight of a ready-to-use cosmetic or pharmaceu thyl-3-carboxamides (e.g. menthyl-3-carboxylic acid tical end product. N-ethylamide), 2-isopropyl-N-2,3-trimethylbutanamide, Particularly preferred mixtures according to the invention Substituted cyclohexanecarboxamides, 3-menthoxypropane are those in which the weight ratio of the total amount of 60 1,2-diol, 2-hydroxyethyl menthyl carbonate, 2-hydroxypro compounds of Formula 1 to the total amount of antidandruff pyl menthyl carbonate, N-acetylglycine menthyl ester, isop agents ranges from 1:100 to 2:1, preferably from 1:50 to 1:1 ulegol, hydroxycarboxylic acid menthyl esters (e.g. menthyl and particularly preferably from 1:10 to 1:2. Thus the propor 3-hydroxybutyrate), monomenthyl Succinate, 2-mercaptocy tion by weight of antidandruff agents is preferably predomi clodecanone, menthyl 2-pyrrolidin-5-onecarboxylate, 2.3- nant compared with that of the compounds of Formula 1. 65 dihydroxy-p-menthane, 3,3,5-trimethylcyclohexanone glyc Particularly preferably, the weight ratio of the com erol ketal, 3-menthyl-3,6-di- and trioxaalkanoates, 3-menthyl pound(s) of Formula 1 to the preferred antidandruff agents, methoxyacetate and icilin. US 8,911,795 B2 15 16 Cooling agents that are preferred on the basis of their Nurturing substances which can particularly preferably be particular synergistic effect are 1-menthol, d-menthol, race combined with the mixtures according to the invention also mic menthol, menthone glycerol acetal (trade name: Fresco include especially lat(R) MGA), menthyl lactate (preferably 1-menthyl lactate, ceramides, which are understood as meaning N-acylsph especially 1-menthyll-lactate (trade name: Frescolat(R) ML)). 5 ingosines (fatty acid amides of sphingosine) or synthetic Substituted menthyl-3-carboxamides (e.g. menthyl-3-car analogues of Such lipids (so-called pseudo-ceramides) boxylic acid N-ethylamide), 2-isopropyl-N-2,3-trimethylbu that markedly improve the water retention capacity of tanamide, Substituted cyclohexanecarboxamides, 3-men the stratum corneum; thoxypropane-1,2-diol, 2-hydroxyethyl menthyl carbonate, phospholipids, e.g. soya lecithin, egg lecithin and cepha 2-hydroxypropyl menthyl carbonate and isopulegol. 10 lins; and petrolatum, paraffin oils and silicone oils, the latter includ Particularly preferred cooling agents are 1-menthol, race ing, inter alia, dialkyl- and alkylarylsiloxanes such as mic menthol, menthone glycerol acetal (trade name: Fresco dimethylpolysiloxane and methyl-phenylpolysiloxane, lat(R) MGA), menthyl lactate (preferably 1-menthyl lactate, and their alkoxylated and quaternized derivatives. especially 1-menthyll-lactate (trade name: Frescolat(R) ML)). 15 Combination with Preservatives, Antiperspirants or Chela 3-menthoxypropane-1,2-diol, 2-hydroxyethyl menthyl car tOrS: bonate and 2-hydroxypropyl menthyl carbonate. Cosmetic preparations containing mixtures according to Very particularly preferred cooling agents are 1-menthol, the invention can also contain active compounds for preserv menthone glycerol acetal (trade name: Frescolater MGA) and ing cosmetic products, antiperspirants and (metal) chelators. menthyl lactate (preferably 1-menthyl lactate, especially Combination with Animal and/or Vegetable Protein Hydro 1-menthyll-lactate (trade name: Frescolater ML)). lyZates: Depending on the Substance, the use concentration of the Animal and/or vegetable protein hydrolyzates can also cooling agents to be used ranges preferably from 0.01 to 20 advantageously be added to the mixtures according to the percent by weight and particularly preferably from 0.1 to 5 invention. The following are particularly advantageous in this percent by weight, based on the total of a ready-to-use cos 25 context: fractions of elastin, collagen, keratin, lactalbumin, metic or pharmaceutical end product. Soya protein, oat protein, pea protein, almond protein and Particularly preferred mixtures according to the invention wheat protein, or corresponding protein hydrolyzates, and are those in which the weight ratio of the total amount of also their condensation products with fatty acids, as well as compounds of Formula 1 to the total amount of cooling agents quaternized protein hydrolyzates, the use of vegetable protein 30 hydrolyzates being preferred. ranges from 1:100 to 1:2, preferably from 1:50 to 1:5 and Combination with Solvents: particularly preferably from 1:30 to 1:10. Thus the proportion If a cosmetic or dermatological preparation containing by weight of cooling agents is preferably predominant com synergistically effective combinations of anthranilic acid pared with that of the compounds of Formula 1. amides and antidandruff agents is a solution or lotion, the Combination with Osmolytes: 35 following solvents can be used: The mixtures according to the invention can also be used water or aqueous solutions; together with osmolytes. Examples of osmolytes which may fatty oils, fats, waxes and other natural and synthetic fatty be mentioned are Substances from the group comprising substances, preferably esters offatty acids with alcohols Sugar alcohols (myoinositol, mannitol, Sorbitol), quaternary of low C number, e.g. with isopropanol, propylene gly amines such as taurine, choline, betaine, betaine glycine, 40 color glycerol, or esters of fatty alcohols with alkanoic ectoin, diglycerol phosphate, phosphorylcholine or glycero acids of low C number or with fatty acids: phosphorylcholines, amino acids such as glutamine, glycine, alcohols, diols or polyols of low C number and their ethers, alanine, glutamate, aspartate or proline, phosphatidyl-cho preferably ethanol, isopropanol, propylene glycol, glyc line, phosphatidylinositol, inorganic phosphates, and poly erol, ethylene glycol, ethylene glycol monoethyl or mers of said compounds, such as proteins, peptides, 45 monobutyl ether, propylene glycol monomethyl, mono polyamino acids and polyols. All osmolytes have a skin mois ethyl or monobutyl ether, diethylene glycol monomethyl turizing action at the same time. or monoethyl ether and analogous products. Combination with Keratolytic Substances: Mixtures of the abovementioned solvents are used in par Preferably, keratolytic substances can also be combined ticular. Water can be an additional component of alcoholic with the mixtures according to the invention. Keratolytic 50 Solvents. compounds include the large group of alpha-hydroxy acids. It Combination with Other Active Compounds: is preferable to use salicylic acid, for example. Cosmetic preparations containing a mixture according to Combination with Nurturing Substances: the invention can also particularly advantageously contain In formulations containing mixtures according to the anti-inflammatory compounds and/or compounds that allevi invention for the topical cosmetic or pharmaceutical treat 55 ate reddening and/or other compounds that alleviate itching, ment of e.g. dry, itchy skin, a high proportion especially of it being possible to use any anti-inflammatory compounds nurturing Substances is also of particular advantage because and/or compounds that alleviate reddening and/or itching of the reduced transepidermal water loss due to lipophilic which are suitable or conventionally used for cosmetic and/or components. In one preferred embodiment the compositions dermatological applications. Steroidal anti-inflammatory contain one or more nurturing animal and/or vegetable fats 60 Substances of the corticosteroid type, e.g. hydrocortisone, and oils such as olive oil, Sunflower oil, refined soya oil, palm hydrocortisone derivatives such as hydrocortisone 17-bu oil, sesame oil, rapeseed oil, almond oil, borage oil, evening tyrate, dexamethasone, dexamethasone phosphate, methyl primrose oil, coconut oil, shea butter, jojoba oil, sperm oil, prednisolone or cortisone, are advantageously used as anti tallow, neatsfoot oil and lard, and optionally other nurturing inflammatory compounds or compounds that alleviate components such as fatty alcohols having 8-30 C atoms. The 65 reddening and/or itching; other steroidal anti-inflammatories fatty alcohols used here can be saturated or unsaturated and can be added to the list. It is also possible to use non-steroidal linear or branched. anti-inflammatories. Examples which should be mentioned US 8,911,795 B2 17 18 here are oxicams such as piroXicam or tenoxicam, salicylates skin and hair, it also being possible for the latter to be used in Such as aspirin, disalcid, Solprin or fendosal; acetic acid the form of a plant extract, e.g. bearberry extract, rice extract, derivatives such as diclofenac, fenclofenac, indomethacin, liquorice root extract or components obtained therefrom by Sulindac, tolmetin or clindanac; fenamates such as mefe enrichment, such as glabridin or licochalcone A, Artocarpus namic, meclofenamic, flufenamic or niflumic; propionic acid extract, extracts of Rumex and Ramulus species, extracts of derivatives such as ibuprofen, naproxen or benoxaprofen; or pine species (Pinus) and extracts of Vitis species, or stilbene pyrazoles such as phenylbutaZone, oxyphenylbutaZone, derivatives obtained therefrom by enrichment, and Saxifraga, febraZone or azapropaZone. A possible alternative is to use mulberry, Scutelleria and/or grape extracts. natural anti-inflammatory Substances or Substances that alle Combination with Skin Tanning Agents: viate reddening and/or itching. Plant extracts, special high 10 Cosmetic preparations containing a mixture according to activity plant extract fractions and high-purity active Sub the invention can also contain compounds with a skin tanning stances isolated from plant extracts can be used. Particular action, it being possible in this context to use any skin tanning preference is afforded to extracts, fractions and active sub compounds which are suitable or conventionally used for stances from camomile, Aloe vera, Commiphora species, cosmetic and/or dermatological applications. An example Rubia species, willow, willow-herb, oats, calendula, arnica, 15 which may be mentioned here is dihydroxyacetone (DHA; St John's wort, honeysuckle, rosemary, Passiflora incarnata, 1,3-dihydroxy-2-propanone). DHA can exist in both mono witch hazel, ginger or Echinacea, and pure Substances Such meric and dimeric form, the proportion of dimer being pre as, interalia, (alpha-)bisabolol, apigenin, apigenin-7-gluco dominant in the crystalline form. side, boswellic acid, phytosterols, glycyrrhizin, glabridin and Combination with Saccharides: licochalcone A. The synergistically effective combinations of Cosmetic preparations containing a mixture according to anthranilic acid amides and antidandruff agents can also con the invention can also contain mono-, di- and oligosaccha tain mixtures of two or more anti-inflammatory compounds. rides, e.g. glucose, galactose, fructose, mannose, fructose and Depending on the Substance, the use concentration of the lactose. anti-inflammatory compounds which can be used ranges Combination with Plant Extracts: from 0.005 to 2% (m/m) and preferably from 0.05 to 0.5% 25 Cosmetic preparations containing a mixture according to (m/m), based on the total weight of a ready-to-use cosmetic or the invention can also contain plant extracts, which are con pharmaceutical end product. These data apply especially to ventionally prepared by extraction of the whole plant or, in bisabolol. specific cases, exclusively from the blossom and/or leaves, Combination with Antioxidants: wood, bark or roots of the plant. Cosmetic preparations containing a mixture according to 30 Combination with Surfactants: the invention can also contain antioxidants, it being possible Cosmetic preparations containing a mixture according to to use any antioxidants which are suitable or conventionally the invention can also contain anionic, cationic, non-ionic used for cosmetic and/or dermatological applications. and/or amphoteric Surfactants, especially when crystalline or Combination with Vitamins: microcrystalline solids, e.g. inorganic micropigments, are to Cosmetic preparations containing a mixture according to 35 be incorporated into the preparations. Surfactants are the invention can also contain vitamins and vitamin precur amphiphilic Substances capable of solubilising organic, non sors, it being possible to use any vitamins or vitamin precur polar Substances in water. The hydrophilic parts of a Surfac sors which are suitable or conventionally used for cosmetic tant molecule are usually polar functional groups, e.g. and/or dermatological applications. - COO, OSO or -SO, while the hydrophobic parts Combination with Skin Lighteners: 40 are normally non-polar hydrocarbon radicals. Surfactants are In numerous cases the formulations according to the inven generally classified according to the type and charge of the tion can advantageously be used in combination with skin hydrophilic part of the molecule. They can be divided into lightening compounds, it being possible according to the four groups: invention to use any skin lightening compounds which are anionic Surfactants, Suitable or conventionally used for cosmetic and/or dermato 45 cationic Surfactants, logical applications. Advantageous skin lightening com amphoteric Surfactants and pounds in this context are kojic acid (5-hydroxy-2-hy non-ionic Surfactants. droxymethyl-4-pyranone), kojic acid derivatives, e.g. kojic Anionic Surfactants normally contain carboxylate, Sulfate acid dipalmitate, arbutin, ascorbic acid, ascorbic acid deriva or Sulfonate groups as functional groups. In aqueous solution tives, hydroquinone, hydroquinone derivatives, resorcinol, 50 they form negatively charged organic ions in an acidic or Sulfur-containing molecules, e.g. glutathione or cysteine, neutral medium. Cationic Surfactants are characterized virtu alpha-hydroxy acids (e.g. citric acid, lactic acid, malic acid) ally exclusively by the presence of a quaternary ammonium and derivatives thereof, N-acetyltyrosine and derivatives, group. In aqueous solution they form positively charged undecenoyl-phenylalanine, gluconic acid, 4-alkylresorci organic ions in an acidic or neutral medium. Amphoteric nols, chromone derivatives such as aloesin, flavonoids, thy 55 Surfactants contain both anionic and cationic groups and mol derivatives, 1-aminoethylphosphinic acid, thiourea accordingly behave like anionic or cationic Surfactants in derivatives, elagic acid, nicotinamide, Zinc salts, e.g. Zinc aqueous Solution, depending on the pH. They have a positive chloride or gluconate, thujaplicin and derivatives, triterpenes charge in a strongly acidic medium and a negative charge in Such as maslinic acid, sterols such as ergosterol, benzofura an alkaline medium. In the neutral pH range, on the other nones such as Senkyunolide, vinyl- and ethylguaiacol, inhibi 60 hand, they are Zwitterionic. Polyether chains are typical of tors of nitrogen oxide synthesis, e.g. L-nitroarginine and non-ionic Surfactants. Non-ionic Surfactants do not form ions derivatives thereof, 2,7-dinitroindazole or thiocitrullin, metal in an aqueous medium. chelators (e.g. C-hydroxy fatty acids, palmitic acid, phytic A. Anionic Surfactants acid, lactoferrin, humic acid, gallic acid, bile extracts, biliru Anionic Surfactants that can advantageously be used are bin, biliverdin, EDTA, EGTA and derivatives thereof), retin 65 acylamino acids (and salts thereof) Such as oids, soy milk, serine protease inhibitors or lipoic acid, or acylglutamates, e.g. sodium acylglutamate, di-TEA palmi other synthetic or natural active compounds for lightening the toylaspartate and sodium caprylic/capric glutamate, US 8,911,795 B2 19 20 acylpeptides, e.g. palmitoyl-hydrolyzed lactoprotein, dimethylamine oxides. Cetyltrimethylammonium salts can Sodium cocoyl-hydrolyzed Soya protein and Sodium/po be used particularly advantageously. tassium cocoyl-hydrolyzed collagen, C. Amphoteric Surfactants sarcosinates, e.g. myristoyl sarcosine, TEA lauroylsarco Amphoteric Surfactants that can advantageously be used sinate, sodium lauroylsarcosinate and Sodium cocoyl 5 a sarcosinate, acyl-fcialkylethylenediamine, e.g. sodium acylamphoac taurates, e.g. sodium lauroyltaurate and Sodium methylco etate, disodium acyl-amphodipropionate, disodium coyltaurate, alkylamphodiacetate, sodium acylampho-hydroxypro acyllactylates, lauroyllactylate, caproylactylate and pylsulfonate, disodium acylamphodiacetate and sodium Stearoylactylate, 10 acyl-amphopropionate, alaninates; N-alkylamino acids, e.g. aminopropylalkylglutamide, carboxylic acids and derivatives, such as alkylaminopropionic acid, Sodium alkylimidodipropi lauric acid, aluminum Stearate, magnesium alkanolate and onate and lauroamphocarboxyglycinate. Zinc undecylenate, D. Non-Ionic Surfactants ester-carboxylic acids, e.g. calcium Stearoylactylate, lau 15 Non-ionic Surfactants that can advantageously be used are reth-6 citrate and sodium PEG-4 lauramidocarboxylate, alcohols, ether-carboxylic acids, e.g. sodium laureth-13 carboxylate alkanolamides such as cocamides MEA/DEA/MIPA, and sodium PEG-6 cocamidocarboxylate: amine oxides such as cocamidopropylamine oxide, phosphoric acid esters and salts, such as DEA oleth-10 phos esters formed by the esterification of carboxylic acids with phate and dilaureth-4 phosphate; ethylene oxide, glycerol, Sorbitan or other alcohols, Sulfonic acids and salts, such as ethers, e.g. ethoxylated/propoxylated alcohols, ethoxy acylisethionates, e.g. sodium/ammonium cocoylisethion lated/propoxylated esters, ethoxylated/propoxylated ate, glycerol esters, ethoxylated/propoxylated cholesterols, alkylarylsulfonates, ethoxylated/propoxylated triglyceride esters, ethoxy alkylsulfonates, e.g. sodium coco monoglyceride Sulfate, 25 lated/propoxylated lanolin, ethoxylated/propoxylated sodium C-a-olefinsulfonate, sodium laurylsulfoac polysiloxanes, propoxylated POE ethers, and alkyl etate and magnesium PEG-3 cocamidosulfate, polyglycosides such as lauryl glucoside, decylglycoside SulfoSuccinates, e.g. sodium dioctylsulfo Succinate, diso and coco glycoside, dium laureth Sulfo Succinate, disodium laurylsulfoSucci Sucrose esters and ethers, nate and disodium MEA undecylenamidosulfosucci 30 polyglycerol esters, diglycerol esters and monoglycerol nate; esters, and methylglucose esters and esters of hydroxy acids. Sulfuric acid esters such as The use of a combination of anionic and/or amphoteric alkyl ether sulfate, e.g. sodium, ammonium, magnesium, Surfactants with one or more non-ionic Surfactants is also MIPA and TIPA laureth sulfate, sodium myreth sulfate 35 advantageous. and sodium C12-13 pareth sulfate, The Surface-active Substance can be present in a concen alkylsulfates, e.g. sodium, ammonium and TEA laurylsul tration of between 1 and 98% (m/m) in the preparations fate. containing Synergistically effective combinations of anthra B. Cationic Surfactants nilic acid amides and antidandruff agents, based on the total Cationic Surfactants that can advantageously be used are 40 weight of the preparations. alkylamines, Emulsions Comprising a Mixture According to the Invention: alkylimidazoles, Cosmetic or dermatological preparations containing syn ethoxylated amines and ergistically effective combinations according to the invention quaternary Surfactants: of anthranilic acid amides and antidandruff agents can also 45 take the form of emulsions. RNHCH-CHCOO (at pH 7) The oily phase can advantageously be selected from the following group of Substances: mineral oils and mineral waxes; RNHCH-CHCOOB" (at pH 12), fatty oils, fats, waxes and other natural and synthetic fatty B'-arbitrary cation, e.g. Na' 50 substances, preferably esters offatty acids with alcohols esterquats of low C number, e.g. with isopropanol, propylene gly Quaternary Surfactants contain at least one Natom that is color glycerol, or esters of fatty alcohols with alkanoic covalently bonded to 4 alkyl or aryl groups. This produces a acids of low C number or with fatty acids: positive charge, irrespective of the pH. Alkylbetaine, alkyla alkylbenzoates; midopropylbetaine and alkylamidopropylhydroxysulfaine 55 silicone oils such as dimethylpolysiloxanes, diethylpolysi are advantageous. The cationic Surfactants used can also pref loxanes, diphenyl-polysiloxanes and mixed forms erably be selected from the group comprising quaternary thereof. ammonium compounds, in particular benzyltrialkylammo (a) Esters of Saturated and/or unsaturated, branched and/or nium chlorides or bromides, e.g. benzyldimethylstearylam unbranched alkanecarboxylic acids having a chain length of 3 monium chloride, and also alkyltrialkylammonium salts, e.g. 60 to 30 C atoms and saturated and/or unsaturated, branched cetyltrimethylammonium chloride or bromide, alkyldimeth and/or unbranched alcohols having a chain length of 3 to 30C ylhydroxyethylammonium chlorides or bromides, dialky atoms, and (b) esters of aromatic carboxylic acids and Satu ldimethylammonium chlorides or bromides, alkylamidoet rated and/or unsaturated, branched and/or unbranched alco hyl-trimethylammonium ether Sulfates, alkylpyridinium hols having a chain length of 3 to 30 C atoms, can advanta salts, e.g. lauryl- or cetyl-pyrimidinium chloride, imidazoline 65 geously be used. Preferred ester oils are isopropyl myristate, derivatives and compounds of acationic nature, Such as amine isopropyl palmitate, isopropyl Stearate, isopropyl oleate, oxides, e.g. alkyldimethylamine oxides or alkylaminoethyl n-butyl Stearate, n-hexyl laurate, n-decyl oleate, isooctyl US 8,911,795 B2 21 22 Stearate, isononyl Stearate, isononyl isononanoate, 3.5.5-tri advantageously be selected from the group comprising poly methylhexyl 3.5.5-trimethylhexanoate, 2-ethylhexyl ethoxylated or polypropoxylated or polyethoxylated and isononanoate, 2-ethylhexyl 3.5.5-trimethylhexanoate, 2-eth polypropoxylated products, e.g.: ylhexyl 2-ethylhexanoate, 2-ethylhexyl palmitate, 2-ethyl fatty alcohol ethoxylates, hexyl laurate, 2-hexyldecyl Stearate, 2-octyldodecyl palmi 5 ethoxylated wool wax alcohols, tate, oleyl oleate, oleylerucate, erucyl oleate, erucyl erucate polyethylene glycol ethers of the general formula and synthetic, semisynthetic and natural mixtures of Such esters, e.g. jojoba oil. R—O—(—CH2—CH2—O—), R, Furthermore, the oily phase can advantageously be fatty acid ethoxylates of the general formula selected from the group comprising branched and 10 unbranched hydrocarbons and waxes, silicone oils, dialkyl R—COO—(—CH2—CH2—O—), H, ethers, the group comprising saturated or unsaturated, etherified fatty acid ethoxylates of the general formula branched or unbranched alcohols, and also fatty acid triglyc erides, specifically the triglycerol esters of Saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic 15 esterified fatty acid ethoxylates of the general formula acids having a chain length of 8 to 24 and especially 12 to 18 C atoms. The fatty acid triglycerides can advantageously be selected from the group comprising synthetic, semisynthetic polyethylene glycol glycerol fatty acid esters, and natural oils, e.g. olive oil, Sunflower oil, Soya oil, ground ethoxylated sorbitan esters, nut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm cholesterol ethoxylates, kernel oil and the like. Arbitrary mixtures of such oil and wax ethoxylated triglycerides, components can also advantageously be used. In some cases alkyl ether carboxylic acids of the general formula it is also advantageous to use waxes, e.g. cetyl palmitate, as the Sole lipid component of the oily phase; advantageously, where n is a number from 5 to 30, the oily phase is selected from the group comprising 2-ethyl 25 hexyl isostearate, octyldodecanol, isotridecyl isononanoate, polyoxyethylene sorbitol fatty acid esters, isoeicosane, 2-ethylhexyl cocoate, C-s-alkyl benzoate, alkyl ether sulfates of the general formula caprylic/capric triglyceride and dicaprylyl ether. Mixtures of R-O-(—CH2—CH2—O ), SO. H., Cis-alkylbenzoate and 2-ethylhexyl isostearate, mixtures fatty alcohol propoxylates of the general formula of C-s-alkyl benzoate and isotridecyl isononanoate and 30 mixtures of C-s-alkyl benzoate, 2-ethylhexyl isostearate R—O—(—CH2—CH(CH3)—O—)—H, and isotridecyl isononanoate are particularly advantageous. polypropylene glycol ethers of the general formula The hydrocarbons paraffin oil, squalane and squalene can also advantageously be used. Advantageously, the oily phase can further contain cyclic or linear silicone oils or consist 35 propoxylated wool wax alcohols, entirely of such oils, although it is preferable to use other oily etherified fatty acid propoxylates phase components in addition to the silicone oil(s). Cyclom ethicone (e.g. decamethylcyclopentasiloxane) can advanta R—COO—(—CH2—CH(CH3)—O—)—R', geously be used as a silicone oil. However, other silicone oils esterified fatty acid propoxylates of the general formula can also advantageously be used, examples being undecam 40 ethylcyclotrisiloxane, poly-dimethylsiloxane and poly(meth ylphenylsiloxane). Furthermore, mixtures of cyclomethicone fatty acid propoxylates of the general formula and isotridecyl isononanoate and of cyclomethicone and 2-ethylhexyl isostearate are particularly advantageous. R—COO—(—CH2—CH(CH3)—O—)—H, The aqueous phase of preparations that contain synergis 45 polypropylene glycol glycerol fatty acid esters, tically effective combinations of anthranilic acid amides and propoxylated Sorbitan esters, antidandruff agents and take the form of an emulsion can cholesterol propoxylates, advantageously comprise alcohols, diols or polyols of low C propoxylated triglycerides, number, as well as ethers thereof, preferably ethanol, isopro alkyl ether carboxylic acids of the general formula panol, propylene glycol, glycerol, ethylene glycol, ethylene 50 glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene gly alkyl ether sulfates and the acids on which these sulfates col monomethyl or monoethyl ether and analogous products, are based of the general formula and also alcohols of low C number, e.g. ethanol, isopropanol, 1.2-propanediol and glycerol, and in particular one or more 55 thickeners, which can advantageously be selected from the fatty alcohol ethoxylates/propoxylates of the general for group comprising silicon dioxide, aluminum silicates, mula polysaccharides and derivatives thereof, e.g. hyaluronic acid, R—O—X, Y, H., Xanthan gum, hydroxypropyl methyl cellulose, and particu larly advantageously from the group comprising polyacry 60 polypropylene glycol ethers of the general formula lates, preferably a polyacrylate from the group comprising the R-O X, Y R', so-called carbopols, e.g. carbopols of types 980, 981, 1382, 2984 and 5984, in each case on their own or in combination. etherified fatty acid propoxylates of the general formula Preparations that contain synergistically effective combi R—COO X, Y R', nations of anthranilic acid amides and antidandruff agents 65 and take the form of an emulsion advantageously comprise fatty acid ethoxylates/propoxylates of the general formula one or more emulsifiers. O/W emulsifiers can, for example, R—COO X, Y, H. US 8,911,795 B2 23 24 According to the invention, the polyethoxylated or ene glycol (19) isostearate, polyethylene glycol (20) isostear polypropoxylated or polyethoxylated and polypropoxylated ate, polyethylene glycol (21) isostearate, polyethylene glycol O/W emulsifiers used are particularly advantageously (22) isostearate, polyethylene glycol (23) isoStearate, poly selected from the group comprising Substances having HLB ethylene glycol (24) isostearate, polyethylene glycol (25) values of 11-18, very particularly advantageously having isostearate, polyethylene glycol (12) oleate, polyethylene HLB values of 14.5-15.5, if the O/W emulsifiers contain glycol (13) oleate, polyethylene glycol (14) oleate, polyeth saturated radicals R and R. If the O/W emulsifiers contain ylene glycol (15) oleate, polyethylene glycol (16) oleate, unsaturated radicals R and/or R', or if isoalkyl derivatives are polyethylene glycol (17) oleate, polyethylene glycol (18) ole present, the preferred HLB value of such emulsifiers can also ate, polyethylene glycol (19) oleate and polyethylene glycol be lower or higher. It is advantageous to select the fatty 10 (20) oleate. alcohol ethoxylates from the group comprising ethoxylated Sodium laureth-11 carboxylate can advantageously be Stearyl alcohols, cetyl alcohols and cetylstearyl alcohols (cet used as an ethoxylated alkyl ether carboxylic acid or a salt earyl alcohols). The following are particularly preferred: thereof. Sodium laureth 1-4 sulfate can advantageously be polyethylene glycol (13) stearyl ether (steareth-13), poly used as an alkyl ether sulfate. Polyethylene glycol (30) cho ethylene glycol (14) stearyl ether (steareth-14), polyethylene 15 lesteryl ether can advantageously be used as an ethoxylated glycol (15) stearyl ether (steareth-15), polyethylene glycol cholesterol derivative. Polyethylene glycol (25) soyasterol (16) stearyl ether (steareth-16), polyethylene glycol (17) has also proved useful. stearyl ether (steareth-17), polyethylene glycol (18) stearyl Polyethylene glycol (60) evening primrose glycerides can ether (steareth-18), polyethylene glycol (19) stearyl ether advantageously be used as ethoxylated triglycerides. (steareth-19), polyethylene glycol (20) stearyl ether (ste It is also advantageous to select the polyethylene glycol areth-20), polyethylene glycol (12) isostearyl ether (isoste glycerol fatty acid esters from the group comprising polyeth areth-12), polyethylene glycol (13) isostearyl ether (isoste ylene glycol (20) glyceryl laurate, polyethylene glycol (21) areth-13), polyethylene glycol (14) isostearyl ether glyceryl laurate, polyethylene glycol (22) glyceryl laurate, (isosteareth-14), polyethylene glycol (15) isostearyl ether polyethylene glycol (23) glyceryl laurate, polyethylene gly (isosteareth-15), polyethylene glycol (16) isostearyl ether 25 col (6) glyceryl caprylate/caprate, polyethylene glycol (20) (isosteareth-16), polyethylene glycol (17) isostearyl ether glyceryl oleate, polyethylene glycol (20) glyceryl isostearate (isosteareth-17), polyethylene glycol (18) isostearyl ether and polyethylene glycol (18)glyceryl oleate/cocoate. (isosteareth-18), polyethylene glycol (19) isostearyl ether It is likewise favorable to select the sorbitan esters from the (isosteareth-19), polyethylene glycol (20) isostearyl ether group comprising polyethylene glycol (20) Sorbitan mono (isosteareth-20), polyethylene glycol (13) cetyl ether (ceteth 30 laurate, polyethylene glycol (20) Sorbitan monostearate, 13), polyethylene glycol (14) cetyl ether (ceteth-14), polyeth polyethylene glycol (20) Sorbitan monoisoStearate, polyeth ylene glycol (15) cetyl ether (ceteth-15), polyethylene glycol ylene glycol (20) sorbitan monopalmitate and polyethylene (16) cetyl ether (ceteth-16), polyethylene glycol (17) cetyl glycol (20) Sorbitan monooleate. ether (ceteth-17), polyethylene glycol (18) cetyl ether (cet The following can be used as advantageous W/O emulsi eth-18), polyethylene glycol (19) cetyl ether (ceteth-19), 35 fiers: fatty alcohols having 8 to 30 carbon atoms, monoglyc polyethylene glycol (20) cetyl ether (ceteth-20), polyethylene erol esters of Saturated and/or unsaturated, branched and/or glycol (13) isocetyl ether (isoceteth-13), polyethylene glycol unbranched alkanecarboxylic acids having a chain length of 8 (14) isocetyl ether (isoceteth-14), polyethylene glycol (15) to 24, in particular 12 to 18 C atoms, diglycerol esters of isocetyl ether (isoceteth-15), polyethylene glycol (16) iso saturated and/or unsaturated, branched and/or unbranched cetyl ether (isoceteth-16), polyethylene glycol (17) isocetyl 40 alkanecarboxylic acids having a chain length of 8 to 24, in ether (isoceteth-17), polyethylene glycol (18) isocetyl ether particular 12 to 18 C atoms, monoglycerol ethers of saturated (isoceteth-18), polyethylene glycol (19) isocetyl ether (iso and/or unsaturated, branched and/or unbranched alcohols ceteth-19), polyethylene glycol (20) isocetyl ether (isoceteth having a chain length of 8 to 24, in particular 12 to 18 C atoms, 20), polyethylene glycol (12) oleyl ether (oleth-12), polyeth diglycerol ethers of Saturated and/or unsaturated, branched ylene glycol (13) oleyl ether (oleth-13), polyethylene glycol 45 and/or unbranched alcohols having a chain length of 8 to 24, (14) oleyl ether (oleth-14), polyethylene glycol (15) oleyl in particular 12 to 18 C atoms, propylene glycol esters of ether (oleth-15), polyethylene glycol (12) lauryl ether (lau saturated and/or unsaturated, branched and/or unbranched reth-12), polyethylene glycol (12) isolauryl ether (isolaureth alkanecarboxylic acids having a chain length of 8 to 24, in 12), polyethylene glycol (13) cetylstearyl ether (ceteareth particular 12 to 18 C atoms, and sorbitan esters of saturated 13), polyethylene glycol (14) cetylstearyl ether (ceteareth 50 and/or unsaturated, branched and/or unbranched alkanecar 14), polyethylene glycol (15) cetylstearyl ether (ceteareth boxylic acids having a chain length of 8 to 24, in particular 12 15), polyethylene glycol (16) cetylstearyl ether (ceteareth to 18 C atoms. 16), polyethylene glycol (17) cetylstearyl ether (ceteareth Particularly advantageous W/O emulsifiers are glyceryl 17), polyethylene glycol (18) cetylstearyl ether (ceteareth monostearate, glyceryl monoisoStearate, glyceryl mono 18), polyethylene glycol (19) cetylstearyl ether (ceteareth 55 myristate, glyceryl monooleate, diglyceryl monostearate, 19) and polyethylene glycol (20) cetylstearyl ether diglyceryl monoisoStearate, propylene glycol monostearate, (ceteareth-20). propylene glycol monoisoStearate, propylene glycol mono It is also advantageous to select the fatty acid ethoxylates caprylate, propylene glycol monolaurate, Sorbitan monoisos from the following group: tearate, Sorbitan monolaurate, Sorbitan monocaprylate, Sorbi polyethylene glycol (20) Stearate, polyethylene glycol (21) 60 tan monoisooleate, Sucrose distearate, cetyl alcohol, Stearyl Stearate, polyethylene glycol (22) Stearate, polyethylene gly alcohol, arachidyl alcohol, behenyl alcohol, isobelhenyl alco col (23) Stearate, polyethylene glycol (24) Stearate, polyeth hol, Selachyl alcohol, chimyl alcohol, polyethylene glycol (2) ylene glycol (25) Stearate, polyethylene glycol (12) isostear Stearyl ether (Steareth-2), glyceryl monolaurate, glyceryl ate, polyethylene glycol (13) isostearate, polyethylene glycol monocaprate and glyceryl monocaprylate. (14) isostearate, polyethylene glycol (15) isostearate, poly 65 Preferred Formulations: ethylene glycol (16) isostearate, polyethylene glycol (17) The mixtures according to the invention can be incorpo isostearate, polyethylene glycol (18) isostearate, polyethyl rated without difficulty into conventional cosmetic or derma US 8,911,795 B2 25 26 tological/keratological formulations such as, interalia, pump e.g. to a perfumed finished product. Particularly preferred sprays, aerosol sprays, creams, shampoos, ointments, tinc perfume compositions comprise (a) a sensorially effective tures, lotions, nail care products (e.g. nail varnishes, nail amount of a perfume, (b) an itch-regulating, antiallergic and/ varnish removers, nail balsams) and the like. In this context it or hyposensitizing amount of a synergistically effective mix is also possible, and in some cases advantageous, to combine 5 ture of anthranilic acid amides and antidandruff agents, and the synergistically effective combinations of anthranilic acid (c) optionally one or more excipients and/or additives. Since amides and antidandruff agents with other active compounds. the proportion of perfume in a cosmetic finished product is In this context the cosmetic and/or dermatological/kerato frequently in the region of approx. 1% (m/m), a perfume logical formulations containing synergistically effective containing a compound of Formula 1 according to the inven combinations of anthranilic acid amides and antidandruff 10 tion will preferably contain about 0.1-10% (m/m) of one or agents can otherwise be of conventional composition and be more compounds of Formula 1. It has proved particularly used for treatment of the skin and/or hair in the sense of a advantageous that the Synergistically effective combinations dermatological/keratological treatment or a treatment in the sense of care cosmetics. However, the synergistically effec of anthranilic acid amides and antidandruff agents have only tive combinations of anthranilic acid amides and antidandruff 15 a weak inherent odor or are even completely odorless, since agents can also be used in make-up products in decorative this property predestines them in particular for use in a per cosmetics. fume composition. Combination with Sunscreens: Preferred embodiments of the mixtures according to the For use, the cosmetic and/or dermatological/keratological invention and of the processes and uses according to the formulations containing a mixture according to the invention invention can be seen from the following examples and cor are applied to the skin and/or hair in an adequate amount in responding tables: the manner conventionally used for cosmetics and dermato logical products. In this context cosmetic and dermatological preparations that contain a mixture according to the invention EXAMPLES and additionally act as a Sunscreen also offer particular 25 advantages. Advantageously, these preparations contain at The intensification of the itch-alleviating efficacy of the least one UVA filter and/or at least one UVB filter and/or at active compound combinations according to the invention is least one inorganic pigment. In this case the preparations can apparent from the human in vivo studies described below. take various forms such as those conventionally employed for Unless indicated otherwise, all the amounts are given in 96 by preparations of this type. Thus they can be e.g. a solution, an 30 weight. emulsion of the water-in-oil (W/O) type or of the oil-in-water (O/W) type or a multiple emulsion, e.g. of the water-in-oil in-water (W/O/W) type, a gel, a hydrodispersion, a solid stick Example 1 or else an aerosol. Combination with Cosmetic Auxiliaries: 35 Detection of the intensified efficacy of a shampoo formu In cosmetic preparations, the mixtures according to the lation consisting of an itch-alleviating compound (dihydroav invention can advantageously also be combined with cos enanthramide D; CARN: 697235-49-7: 2-3-(4-hydrox metic auxiliaries Such as those conventionally used in Such yphenyl)-1-oxopropylaminobenzoic acid (9Cl)) and an preparations, e.g. antioxidants, perfume oils, antifoams, colo antidandruff agent (climbazole; Symrise trade name: Crin rants, pigments with a coloring action, thickeners, Surface 40 ipan) compared with a shampoo formulation containing only active Substances, emulsifiers, plasticizers, other moisturiz an antidandruff agent (climbazole; Symrise trade name: Crin ing and/or moisture-retaining Substances, fats, oils, waxes or ipan) other conventional components of a cosmetic formulation, Such as alcohols, polyols, polymers, foam stabilizers, elec 45 trolytes, organic solvents or silicone derivatives. According to the invention, any conceivable antioxidants, perfume oils, antifoams, colorants, pigments with a coloring action, thick eners, Surface-active Substances, emulsifiers, plasticizers, N moisturizing and/or moisture-retaining Substances, fats, oils, 50 CO2H waxes, alcohols, polyols, polymers, foam stabilizers, electro HO lytes, organic solvents or silicone derivatives that are Suitable structural formula: dihydroavenanthramide D (= compound 8) or conventionally used for cosmetic and/or dermatological applications can be used here. 55 As regards other cosmetic and pharmaceutical active com Description of the Test Method: pounds, bases and auxiliaries which can particularly prefer ably be combined with the synergistically effective combina The tests were carried out on 24 subjects. tions according to the invention of anthranilic acid amides Samples: and antidandruff agents, reference may be made to the 60 1. Shampoo formulation 1 containing 0.2% by weight of the detailed descriptions in WO 2004/047833 and WO O3FO69994. antidandruff compound climbazole (sample reference: Combination with Perfumes: GS05053SL-A) The mixtures according to the invention can also be used as 2. Shampoo formulation 2 containing 0.2% by weight of the a component of perfume compositions for hair and Scalp care 65 antidandruff compound climbazole and 0.05% of the itch products and, especially because of their specific efficacy, can alleviating compound dihydroavenanthramide D (sample ref impart an additional itch-alleviating or antiallergic property erence: GS05053SL-C) US 8,911,795 B2 28 Formulations TABLE 1 Detection of the intensified efficacy of a shampoo formulation consisting % by weight of an itch-alleviating compound (dihydroaven-anthramide D) and an antidandruff agent (climbazole; Symrise trade name: Crinipan) compared 5 GSOSOS3SLC with a shampoo formulation containing only an antidandruff agent 0.2% of climbazole Start after 21 days after 42 days GSO5053SLA and 0.05% of 0.2% of dihydroaven GSOSOS3SL-A 4 3.7 3.5 GSOSOS3SL-C 4.1 3.3 2.4 Raw materials: INCI name climbazole anthramide D 10 A. Crinipan AD Climbazole O.2 O.2 Itching scale: Butylene glycol Butylene Glycol O.S 1 (no itching); Hydrolite-5 Pentylene Glycol O.S 2 (slight); Dragocid liquid Phenoxyethanol O.S O.S 3 (moderate); Methyl-, Ethyl-, 4 (intense); Butyl-, Propyl-, 15 5 (very intense); Isobutylparaben 6 (extremely intense) B. Water, Water (Aqua) Ad 100 Ad 100 demineralized C. Result: Sodium Sodium Chloride O.8 O.8 1. Product GS05053SL-A shows only a low efficacy in the chloride reduction of itching. Plantacare Sodium Laureth 2O.O 2O.O 2O Product GS05053SL-C shows a significantly better effi PS 10 Sulfate (and) Lauryl Glycoside cacy than product GS05053SL-A in the reduction of itching Dihydroaven- Dihydro- O.OS (Table 1). The intensity of itching could be reduced to a value anthramide D avenanthramide D of 2.4 after 42 days with product GS05053SL-C. Dehyton K Cocoamidopropyl 8.0 8.0 Example 2 Betaine 25 C. Citric acid, Citric Acid 1.O 1.O Detection of the synergistically intensified efficacy of a 10% solution shampoo formulation consisting of an itch-alleviating com Total 1OO.O 1OOO pound (dihydroavenanthramide D) and an antidandruff agent pH: 6.0 6.O (climbazole; Symrise trade name: Crinipan) compared with a 30 shampoo formulation containing only an antidandruff agent (climbazole; Symrise trade name: Crinipan) and compared Experimental Procedure with a shampoo formulation containing only an itch-alleviat ing compound (dihydroavenanthramide D) A. Preconditioning Description of the Test Method: The subjects were preconditioned over a period of 14 days, is The tests were carried out on 36 subjects. during which they used a standard shampoo not containing Samples: active compounds. The application of other cosmetic agents 1. Shampoo formulation A containing 0.4% by weight of the to the scalp was not permitted during this period. antidandruff compound climbazole (sample reference: GS05053SL-A) B. Test Period 2. Shampoo formulation B containing 0.1% by weight of the 12 subjects used shampoo GS05053SL-A and 12 used 40 itch-alleviating compound dihydroavenanthramide D shampoo GS05053SL-C over a total test period of 42 days. (sample reference: GS05053SL-B) 3. Shampoo formulation C containing 0.2% by weight of the The hair and scalp were treated once every other day with the antidandruff compound climbazole and 0.05% of the itch appropriate product. alleviating compound dihydroavenanthramide D (sample ref Test parameter: reduction of itching (Subjective feeling of 45 erence: GS05053SL-C) the subjects) Formulations

% by weight

GSOSO98SLC 0.2% of GSOSO98SLB climbazole GSOSO98SLA 0.10% of O.05% of 0.4% of dihydroaven- dihydroaven Raw materials: INCI name climbazole anthramide D anthramide D

A. Crinipan AD Climbazole 0.4 O.2 Butylene glycol Butylene Glycol O.S Hydrolite-5 Pentylene Glycol O.S Dragocid liquid Phenoxyethanol O.S O.S O.S Methyl-, Ethyl-, Butyl-, Propyl-, Isobutylparaben B. Water, demineralized Water (Aqua) Ad 100 Ad 100 Ad 100 Sodium chloride Sodium Chloride O.8 O.8 O.8 Plantacare PS 10 Sodium Laureth 2O.O 2O.O 2O.O Sulfate (and) Lauryl Glycoside US 8,911,795 B2

-continued % by weight

GSOSO98SLC 0.2% of GSOSO98SLB climbazole GSOSO98SLA 0.10% of O.05% of 0.4% of dihydroaven- dihydroaven Raw materials: INCI name climbazole anthramide D anthramide D Dihydroavenanthramide D Dihydro- O.1 O.OS (compound 8) avenanthramide D Dehyton K Cocoamidopropyl 8.0 8.0 8.O Betaine C. Citric acid, 10% solution Citric Acid 1.O 1.O 1.O

Total 1OO.O 1OO.O 1OO.O pH: 6.0 6.0 6.O

Experimental Procedure TABLE 2-continued A. Preconditioning 2O Detection of the synergistically intensified efficacy of a shampoo formulation The subjects were preconditioned over a period of 14 days, consisting of an itch-alleviating compound (dihydroavenanthramide D) during which they used a standard shampoo not containing and an antidandruff agent(climbazole; Symrise trade name: Crinipan) active compounds. The application of other cosmetic agents compared with a shampoo formulation containing only an antidandruff to the scalp was not permitted during this period. agent and compared with a formulation containing only an B. Test Period 25 itch-alleviating compound 12 subjects used shampoo GS05098SL-A, 12 used sham Start after 21 days after 42 days poo GS05098SL-B and 12 used shampoo GS05098SL-C over a total test period of 42 days. The hair and scalp were GSOSO98SL-C 4.2 3.2 2.4 treated once every other day with the appropriate product. Itching scale: Test parameter: reduction of itching (subjective feeling of 30 1 (no itching); the subjects) 2 (slight); 3 (moderate); 4 (intense); TABLE 2 5 (very intense); 6 (extremely intense) Detection of the synergistically intensified efficacy of a shampoo formulation 35 consisting of an itch-alleviating compound (dihydroavenanthramide D) C. Result: and an antidandruff agent(climbazole; Symrise trade name: Crinipan) compared with a shampoo formulation containing only an antidandruff Products GSO5098SL-A and GS05098SL-B show a sig agent and compared with a formulation containing only an nificantly lower efficacy than product GS05098SL-C in the itch-alleviating compound reduction of itching. A synergistically intensified efficacy is 40 proven below using the itching reduction factor after 42 days Start after 21 days after 42 days as an example. The calculated synergy index (SI, cf. Table 3) GSOSO98SL-A 4.1 3.8 3.4 of 0.77 clearly shows that the mixture containing 0.05% of GSOSO98SL-B 4.0 3.4 2.9 dihydroavenanthramide D and 0.2% of climbazole represents a synergistic combination of active compounds. TABLE 3 Calculation of the synergy index (SI) after 42 days of a dihydroaven-anthramide D climbazole mixture (product C) consisting of the comparative anti-dandruff compound (A) and the comparative itch-alleviating compound dihydro-avenanthramide D (product B

C B GSOSO98SL-C A. GSO5098SL-B Climbazole (0.2% GSO5098SL-A Dihydroaven by weight) and Climbazole anthramide D Dihydroaven (0.4% by (0.1% by anthramide D Alleviation of itching after 42 days weight) weight) (0.05% by weight) Alleviation of itching 3.4 2.9 2.4 (intensity Scale: 1-6) 6 = extremely intense 1 = no itching Kull's equation: SI = Cx D/A + C x E/B Alleviation of itching: product A 3.4 Alleviation of itching: product B 2.9 Alleviation of itching: product C 2.4 D: proportion of A in C O.S E: proportion of B in C O.S SI: Synergy index O.76 US 8,911,795 B2 31 32 Literature: Synergy Index: Formulations: D. C. Steinberg; Cosmetics & Toiletries 115(11); pp 59-62 (2000) 1-antidandruff shampoo F. C. Kullet al.; Applied Microbiology 9: pp 538-541 (1961) 2–2-in-1 shampoo Example 3 5 3-hair conditioner, leave on Formulations 4=hair conditioner, rinse off 5-hair setting gel Cosmetic formulations containing combinations accord 6-hair care spray, odor absorbing ing to the invention of antidandruffagents and itch-alleviating 10 agents for the improved alleviation of itching are listed by 7=hair oil way of example in Table 4. 8-hair straightening cream TABLE 4 NAME OF RAWMATERIAL FORMULATION 90 BY WEIGHT (Supplier) INCI 1 2 3 4 5 Allantoin Allantoin Merck Aloe veragel Water (Aqua), 1.O concentrate 101 Aloe (Symrise) Barbadensis Leaf Juice AMP-95 (Angus) Aminomethyl 0.7 propanol Antil 141 liquid Propylene 1.O (Degussa-Goldschmidt) Glycol, PEG-55 Propylene Glycol Distearate Antil 200 PEG-2OO 1.5 (Degussa-Goldschmidt) Hydrogenated Glyceryl Palmitate, PEG-7 Glyceryl Cocoate Bisabolol, linka alpha Bisabolol (Symrise) Carbopol ETD 2001 Carbomer 0.7 (Noveon) Cetiol OE Dicaprylyl Ether 7.2 (Cognis) Dracorin GMS Glyceryl (Symrise) Stearate Cetiol S Diethylhexyl 7.0 (Cognis) cyclohexane Cremogen Alpha Pulp Water (Aqua), 1.O (Symrise) Butylene Glycol, Malic Acid, Prints Amygdalus Dulcis (Sweet Almond) Seed Extract, Actinidia Chinensis (Kiwi) Fruit Juice, Citrus Atiraniitin Dulcis (Orange) Juice, Citrus Paradisi (Grapefruit) Juice, Pyrus Maius (Apple) Juice, PEG-40 Hydrogenated Castor Oil Criniipan AD Climbazole O.S O.1 O.3 Dehyguart ACA Cetrimonium 4.0 (Cognis) Chloride Dehyton K (Cognis) Cocoamido- 6.O 8.0 propyl Betaine Dihydroavenanthramide D Dihydroaven- O.OS O.OS O.OS O.OS O.OS O.OS O.OS (Symrise) anthramide D D-Panthenol 7SL Panthenol 1.O 1.O (DSM Nutritional) US 8,911,795 B2 33 34 TABLE 4-continued

NAME OF RAWMATERIAL FORMULATION 9/o BY WEIGHT

(Supplier) INCI 1 2 3 4 5 6 7 8 Dracorin CE Glyceryl O.3 Stearate Citrate Dracorin GOC Glyceryl Oleate O.S (Symrise) Citrate Dracorin 100 s.e. P PEG-100 1.O 6.O (Symrise) Stearate, Glyceryl Stearate Drago-Beta-Glucan Water, Butylene O.3 O.3 (Symrise) Glycol, Glycerin, Avena Saiiva (Oat) Kernel Extract Dragocare W PEG-40 O.S 1.O (Symrise) Butyloctanol Wheat Germ Esters, Water (Aqua), Lactic Acid, Tocopherol Dragocid liquid Phenoxy- O.8 O.8 O.8 O.8 O.S (Symrise) ethanol, Methyl-, Ethyl-, Butyl-, Propyl-, Isobutylparaben Dragoderm Glycerin, O.3 1.O 2.O (Symrise) Triticum Vulgare (Wheat) Gluten, Water (Aqua) Dragoxat 89 Ethylhexyl 1.O S.O (Symrise) SOIlonanoate Emulsiphos Potassium Cetyl 2.0 (Symrise) Phosphate, Hydrogenated Palm Glycerides Ethanol.96% Ethanol 3O.O 3O.O O.3 Eumulgin B1 Ceteareth-12 3.5 (Cognis) Euperlan PK 4000 Glycol 1.O 2.5 (Cognis) Distearate, Laureth-4, Cocoamido propyl Betaine Extrapon champagne Water (Aqua), 2.0 GW Glycerin, Wine (Symrise) Extract, Alcohol Extrapone passion Water (Aqua), O.S flower Propylene (Symrise) Glycol, Passiflora Incarnata Extract, Glucose Farnesol Farnesol O.3 O.1 (Symrise) Frescolat ML Menthyl Lactate O.S O.3 O.S (Symrise) Genapol LRO liquid Sodium Laureth 3S.O (Clariant) Sulfate Glycerol, 99.5% Glycerin 1O.O Hair conditioner base Cetyl Alcohol, 3.0 (Symrise) Behentrimonium Chloride, Triticum Vulgare (Wheat) Bran Extract, Linoleic Acid Hydrolite-5 Pentylene O.S O.S 1.O (Symrise) Glycol Isoadipate Diisopropyl O.S O.3 (Symrise) Adipate Isodragol Trisononanoin 1.O 3.0 (Symrise) US 8,911,795 B2 35 36 TABLE 4-continued

NAME OF RAWMATERIAL FORMULATION 9/o BY WEIGHT

(Supplier) NCI 1 2 3 4 5 6 7 8 PCL liquid 100 Cetearyl O.2 2.0 (Symrise) Octanoate Luviskol K30 powder PVP 3.0 (BASF AG) Luwiskol VA 37 E PVPVA 3.0 (BASF AG) Copolymer Merquat 550 (Ondeo) Polyguaternium-7 O.S 1.O Mineral oil Mineral Oil 88.8 3.0 Mulsifan RT203.80 C12-15 Pareth- 4.0 (Z&S) 2 Neo Heliopan AV Ethylhexyl O.S (Symrise) Methoxy cinnamate Neo Heliopan BB Benzophenone-3 O.1 O.1 O.2 (Symrise) Neo Heliopan Hydro Phenyl- O.2 (Symrise) benzimidazole Sulfonic Acid Neo-PCL water soluble Trideceth-9, 1.O N (Symrise) PEG-5 Ethylhexanoate, Water (Aqua) Neutral TE (BASF) Tetrahydroxy- 1.O propyl Ethylene diamine Polyguart H-81 PEG-15 3.0 (Cognis) Cocopolyamine PCL liquid 100 Cetearyl O.S (Symrise) Octanoate Propylene glycol Propylene S.O Glycol Rose CL forte Water (Aqua), O.S (Symrise) Glycerin, PEG-40 Hydrogenated Castor Oil, Rosa Damascena Flower Oil Sodium chloride Sodium O.8 O.S Chloride Sodium hydroxide, 20% Sodium O.2 O.1 O.2 8.0 Sol. Hydroxide Solubilizer PEG-40 2.0 (Symrise) Hydrogenated Castor Oil, Trideceth-9, Propylene Glycol, Water (Aqua) Symdiol 68 2 Hexanediol, 1.O (Symrise) Caprylylglycol Symrise fragrance Fragrance O.3 O.3 O.3 O.2 0.4 O.2 O.S Texapon N 70 (Cognis) Sodium Laureth 1O.O Sulfate Water, demineralized Water (Aqua) Ad 100 Ad 100 Ad 100 Ad 100 Ad 100 Ad 100 Ad 100 Ad 100

Particularly preferred areas of application for the mixtures Specific Embodiments according to the invention are cosmetic products for treating itchy, dry skin, in particular an itchy, dry scalp, including In specific embodiment one, the invention is a mixture especially antidandruff shampoos and other hair and scalp 55 comprising or consisting of: care products, such as all conceivable types of shampoo (in (a) one or more compounds of Formula 1: cluding shampoos for normal hair, greasy hair and dry, coarse (damaged) hair, 2-in-1 shampoo, baby shampoo, shampoo for dry scalp, shampoo concentrate), conditioners, hair treat Yp ments, hair lotions, hair rinses, hair creams, pomades, perm 60 ing and setting agents, hair Smoothing agents (straightening RI O 21 A. agents, relaxers), hairsprays, styling aids (e.g. gels or waxes): bleaching agents, hair colorants, e.g. temporary, direct hair N pi N S colorants, semipermanent hair colorants, permanent hair X, it H colorants; perming preparations and perming-setting agents: 65 2 R2 COOR3 and pharmaceutical agents for combating diseases/scalp damage associated with itching. US 8,911,795 B2 37 38 where the symbols in the compound or each compound of -continued Formula 1 are defined as follows: m=0, 1, 2 or 3, OH p=0, 1 or 2, n=0, 1 or 2, HO N 1s 1s 1n where, when n=1 or 2, R' and R in pairs are each H or N together are another chemical bond; OCO2H where, when m=1, 2 or 3, each X independently of the others HO is OH, Oalkyl or Oacyl, 10 and where, when p=1 or 2, each Y independently of the others OH is OH, Oalkyl or Oacyl, and R=H or alkyl, R=H also representing the corresponding MeO cosmetically or pharmaceutically acceptable salts and Sol N 15 OCO2H Vates, HO and (b) one or more antidandruff agents. OH In specific embodiment two the invention is a mixture as in specific embodiment one, wherein the antidandruff agent(s) c is (are) present in an amount that synergistically intensifies OYYXY.Y Ya Y the itch-alleviating action of the substance(s) of Formula 1. N In specific embodiment three, the invention is a mixture as C 2 H in specific embodiments 1 or 2 wherein the following defini HO tions apply to the compound of Formula 1: 25 O H n=1 or 2 and the sum p+m-0 and/or p+m-0 and X or Y is selected at least once from the group comprising OH and Oacyl. In specific embodiment four, the invention is a mixture as 30 in specific embodiment three wherein the following defini tions apply to the compound of Formula 1: HO and OH 35 with the proviso that X and Y together are selected at least twice from the group comprising OH and Oacyl. In specific embodiment five, the invention is a mixture as in specific embodiments one or two wherein the following defi NN nitions apply to the compound of Formula 1: 40 HO and also: m=1, 2 or 3, with the proviso that X is selected at least once from the group comprising OH and Oacyl, and/or 45 N p=1 or 2, with the proviso that Y is selected at least once from the group HO comprising OH and Oacyl. In specific embodiment six the invention is a mixture as in one of the preceding specific embodiments wherein the fol 50 lowing definitions apply to the compound of Formula 1: and MeO R" and Rare each Hortogether are another chemical bond. N In specific embodiment seven, the invention is a mixture as 55 in specific embodiment three wherein the compound of For mula 1 is selected from the group comprising: HO sCOO2 2HH

60 10

HO S. c N N 65 CO2H O 2 H HO HO Crs

US 8,911,795 B2

-continued -continued 61 21 OH O

N N O H |C H CO2H Cr-OH CO2H HO 62 22 OH 10 O O

N N HO N H H

CO2H 15 CO2H OH HO 63 OH OH 23 O N O H O HO N Cr-OH CO2H H 64 CO2H OH MeO 25 24

O O

N N N H H 30 CO2H CO2H OH HO 65 25 OH O

35 MeO N H Y YX Y. Y. Y. Ya.O CO2H N OYWSYYY Y HO 26 C 2 H OH 40 O

N In specific embodiment eight, the invention is a mixture as H in specific embodiment one or two wherein the following CO2H definition applies to the compound of Formula 1: 45 HO OH n=0. 27 In specific embodiment nine, the invention is a mixture as O in specific embodiment eight wherein the following defini 50 N tion applies to the compound of Formula 1: H m+p 2. CO2H with the proviso that at least two of the substituents X and Y are selected from the group comprising OH and Oacyl. 28 O In specific embodiment ten, the invention is a mixture as in 55 specific embodiments eight or nine wherein the compound of HO N Formula 1 is selected from the group comprising: H CO2H 60 29 O

N N H CO2H 65 CO2H OH

US 8,911,795 B2 48 -continued In specific embodiment fourteen, the invention is mixtures 79 OH as in one of the preceding specific embodiments wherein the O weight ratio of the total amount of compounds of Formula 1 to the total amount of antidandruff agents ranges from 1:100 to 2:1. N H In specific embodiment fifteen, the invention is mixtures as CO2H in one of the preceding specific embodiments wherein the 80 antidandruff agent(s) is (are) selected from the group com OH prising climbazole and other azoles, pyrithione salts, espe 10 cially Zinc pyrithione, ichthyol and octopiroX, and mixtures O of these Substances. In specific embodiment sixteen, the invention is mixtures as in one of the preceding specific embodiments which also N H 15 include a cooling agent from the group comprising 1-menthol, CO2H d-menthol, racemic menthol, menthone glycerol acetal, men thyl lactate (especially 1-menthyl lactate and 1-menthyll-lac tate), substituted menthyl-3-carboxamides, 2-isopropyl-N-2, In specific embodiment eleven, the invention is a mixture 3-trimethylbutanamide, substituted as in specific embodiment one or two wherein the following cyclohexanecarboxamides, 3-menthoxypropane-1,2-diol. definition applies: 2-hydroxyethyl menthyl carbonate, 2-hydroxypropyl men R=CH, or linear or branched alkyl having 2 to 30 C atoms. thyl carbonate, N-acetylglycine menthyl ester, isopulegol, In specific embodiment twelve, the invention is a mixture hydroxycarboxylic acid menthyl esters (e.g. menthyl 3-hy as claimed in one of the preceding specific embodiments droxybutyrate), monomenthyl Succinate, 2-mercaptocyclo wherein the antidandruff agent(s) is (are) selected from the 25 decanone, menthyl 2-pyrrolidin-5-onecarboxylate, 2,3-dihy group comprising: droxy-p-menthane, 3,3,5-trimethylcyclohexanone glycerol one or more azoles, including climbazole, benzimidazole, ketal, 3-menthyl-3,6-di- and trioxaalkanoates, 3-menthyl benzothiazole, bifonazole, butaconazole nitrate, clotri methoxyacetate and icilin, and mixtures of these Substances. mazole, croconazole, eberconazole, econazole, elubiol, In specific embodiment seventeen, the invention is use of a fenticonazole, fluconazole, flutimazole, isoconazole, 30 mixture as in one of the preceding specific embodiments as a ketoconazole, lanoconazole, metronidazole, micona cosmetic composition for the treatment or prevention of itch Zole, neticonazole, omoconazole, oxiconazole nitrate, ing (pruritus) and/or for the reduction of skin reddening O Sertaconazole, Sulconazole nitrate, thioconazole, diaz for the preparation of a drug for the treatment or prevention of oles and triazoles, e.g. terconazole and itraconazole, 35 itching (pruritus) and/or for the reduction of skin reddening. one or more pyrithione salts, including the Sodium, zinc, In specific embodiment eighteen, the invention is a method tin, calcium, magnesium, aluminum and Zirconium salts of alleviating itching and/or reducing skin reddening, com of 1-hydroxy-2-pyrithione, prising the following step: coal tar, Sulfur, selenium sulfides, aluminum chloride, application to the skin of a mixture as in one of specific octopirox (INCI: Piroctone Olamine), cyclopiroxola 40 embodiments one to sixteen in an amount that alleviates mines, undecylenic acid and its metal salts, potassium itching and/or reduces skin reddening. permanganate, Sodium thiosulfate, propylene glycol, In specific embodiment nineteen, the invention is use of an other branched and unbranched aliphatic diols and poly antidandruff agent for the synergistic intensification of the ols (especially 1,2-diols having 5-18 carbon atoms), action of a compound of Formula 1: urea preparations, griseofulvin, 8-hydroxyquinoline, 45 ciloquinol, thiobendazole, thiocarbamates, triclosan, haloprogin, polyenes, hydroxypyridone, morpholine, benzylamine, allylamines (especially terbinafine), tea Yp tree oil, clove oil, coriander oil, palmarosa oil, thyme oil RI O 21 A. and cinnamon oil, as well as ethereal oil of bitter orange, 50 cinnamaldehyde, citronellic acid, farnesol, berberine, N pi N N hinokitiol, tropolone, birch tar oils, ichthyol (sulfonated X, it H shale oil), Sensiva SC-50 (ethylhexyl glycerol), polyg 2 R2 COOR3 lycerol esters, e.g. polyglycerol-3 caprylate, arylalkyl alcohols, e.g. phenylethyl alcohol, 3-phenyl-1-pro 55 panol, Vetikol (4-methyl-4-phenyl-2-pentanol), muguet in the alleviation of itching or the reduction of skin reddening, alcohol (2,2-dimethyl-3-phenylpropanol), Elestab wherein the following definitions apply to the compound of HP-100, azelaic acid, lyticase, isothiazalinones, espe Formula 1: cially octylisothiazalinone, and iodopropynylbutyl car m=0, 1, 2 or 3, bamate (IPBC). 60 p=0, 1 or 2. In specific embodiment thirteen, the invention is a mixture n=0, 1 or 2, as in one of the preceding specific embodiments wherein the where, when n=1 or 2, R' and R in pairs are each H or amount of compound(s) of Formula 1 and/or the amount of together are another chemical bond, antidandruffagent(s), each taken by itself, has no action in the where, when m=1, 2 or 3, each X independently of the others alleviation of itching or the reduction of skin reddening, but 65 is OH, Oalkyl or Oacyl, the total amount of compound(s) of Formula 1 and antidan and where, when p=1 or 2, each Y independently of the others druff agent(s) does have such an action. is OH, Oalkyl or Oacyl, US 8,911,795 B2 49 50 and 4. A method for treating itching (puritus) comprising R—H or alkyl, R=H also representing the corresponding applying a composition as claimed in claim 1 to skin and/or cosmetically or pharmaceutically acceptable salts and sol hair. Vates. 5. A method for reducing skin reddening, comprising What is claimed is: applying a composition as claimed in claim 1 to skin. 1. A composition comprising: 6. A cosmetic orpharmaceutical end product, comprising a (a) dihydroavenanthramide D composition as claimed in claim 1 and at least one carrier or and excipient. (b) climbazole, 7. The composition of claim 1, wherein dihydroavenan wherein the climbazole is present in the amount of 0.01 to 10 thramide D is present in the amount of 0.001 to 0.2 wt.%, 20 wt %, and based on the total weight of the composition. wherein dihydroavenanthramide D is present in the amount 8. The composition of claim 2, wherein the weight ratio of of 0.001 to 1 wt.%, based on the total weight of the the total amount of the dihydroavenanthramide D to the composition. amount of climbazole ranges from 1:10 to 1:2. 2. The composition as claimed in claim 1, wherein the 15 9. The composition of claim3, wherein the cooling agent is weight ratio of the total amount of the dihydroavenanthra present in the amount of 0.01 to 20 wt.%, based on the total mide D to the amount of climbazole ranges from 1:100 to 2:1. weight of the composition. 3. The composition as claimed in claim 1, further compris 10. The composition of claim 3, wherein the cooling agent ing a cooling agent selected from the group consisting of is present in the amount of 0.1 to 5 wt.%, based on the total 1-menthol, d-menthol, racemic menthol, menthone glycerol weight of the composition. acetal, menthyl lactate, 1-menthyl lactate, 1-menthyll-lactate, 11. The composition of claim 1, further comprising one or substituted menthyl-3-carboxamides, 2-isopropyl-N-2,3-tri more other components selected from the group consisting of methylbutanamide, substituted cyclohexanecarboxamides, skin moisture regulators, osmolytes, keratolytic substances, 3-menthoxypropane-1,2-diol, 2-hydroxyethyl menthyl car preservatives, antiperspirants, solvents anti-inflammatory bonate, 2-hydroxypropyl menthyl carbonate, N-acetylgly 25 compounds, antioxidants, vitamins, skin tighteners, skin tan cine menthyl ester, isopulegol, hydroxycarboxylic acid men ning agents, plant extracts, and surfactants. thyl esters, menthyl 3-hydroxybutyrate, monomenthyl 12. The position of claim 1, wherein the composition is in Succinate, 2-mercaptocyclodecanone, menthyl 2-pyrrolidin the form of an emulsion. 5-onecarboxylate, 2,3-dihydroxy-p-menthane, 3,3,5-trim 13. The composition of claim 11 wherein the one or more ethylcyclohexanone glycerol ketal, 3-menthyl-3,6-di- and 30 other components are selected from the group consisting of tioxaalkanoates, 3-menthyl methoxyacetate and icilin, and chelators and animal and/or vegetable hydrolyzates. mixtures thereof. ck k *k k k