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 R 2 COOR 3 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 C O2 H N H1s-1S-1NO 40 63 O H O 55 N HO 45 C O2 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.