US 2008.0050398A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0050398 A1 Bockmuehl et al. (43) Pub. Date: Feb. 28, 2008 (54) COMPOSITION COMPRISING (30) Foreign Application Priority Data BETA-DEFENSIN 2 Mar. 29, 2005 (DE).......................... 10 2005 O14 687.2 (76) Inventors: Dirk Bockmuehl, Wuppertal (DE); Publication Classification He-Marie Hoehne, Duesseldorf (51) Int. Cl. (DE) A6IR 39/02 (2006.01) AOIN 25/00 (2006.01) Correspondence Address: 52) U.S. Cl. ......................................... 424/1901: 424/405 WOODCOCKWASHIBURN LLP (52) s CIRA CENTRE, 12TH FLOOR (57) ABSTRACT 2929 ARCH STREET PHILADELPHIA, PA 19104-2891 (US) The invention relates to compositions comprising at least 9 one peptide with a structure or structural pattern of B-de (21) Appl. No.: 11/864,386 fensin 2 and/or its derivatives, especially human B-defensin 2. The compositions are selected in particular from cosmetic (22) Filed: Sep. 28, 2007 and/or pharmaceutical compositions, cleaning and/or wash ing agents, water-treatment agents and cooling lubricants. Related U.S. Application Data The invention also relates to the use of peptides with a structure or structural pattern of B-defensin 2 and/or its (63) Continuation of application No. PCT/EP2006/ derivatives, especially human f-defensin 2, as an antimi 002760, filed on Mar. 25, 2006. crobial active ingredient in the aforementioned agents. US 2008/0050398 A1 Feb. 28, 2008 COMPOSITION COMPRISING BETA-DEFENSIN 2 0011. There is a need for new antimicrobial agents or compositions containing them, which do not damage the CROSS-REFERENCE TO RELATED skin microflora as comprehensively, to be made available. APPLICATIONS 0012. There is a particular need for making available 0001) This application is a continuation of PCT/EP2006/ antimicrobial agents that are more effective against body 002760 filed Mar. 25, 2006, which claims the benefit of DE odor than the agents known so far and that are selectively 10 2005 014 687.2, filed Mar. 29, 2005, the complete active against the odor-forming microorganisms. disclosures of which are hereby incorporated by reference in their entirety. SUMMARY OF THE INVENTION 0013 The invention features compositions comprising at FIELD OF THE INVENTION least one B-defensin 2 polypeptide. In some aspects, the polypeptide has SEQ ID NO:1, or a derivative thereof, 0002 The object of the present invention is compositions wherein X of SEQ ID NO:1 is selected independently from comprising at least one peptide having a structure or a the group of the essential and non-essential amino acids. X structural pattern of B-defensin 2 and/or its derivatives, can be Cys, Gly, Thr, or Lys. X can be independently Thr or especially human B-defensin 2. In particular, the composi Gly at position 29, Cys at position 8, 15, 20, 30, 37, or 38, tions are selected from cosmetic and/or pharmaceutical or Lys at position 39 or 40. preparations, washing and/or cleaning agents, water-treat ment agents and cooling lubricants. A further object of the 0014. In some aspects, the compositions comprise at least invention is the use of at least one peptide with a structure one B-defensin 2 polypeptide having SEQ ID NO:2, or a or a structural pattern of B-defensin 2 and/or its derivatives, derivative thereof. In some aspects, the compositions com especially human B-defensin 2, as an antimicrobial agent in prise at least one f-defensin 2 polypeptide having SEQ ID the means listed. NO:3, or a derivative thereof. 0015. In the inventive compositions, the B-defensin 2 BACKGROUND OF THE INVENTION polypeptide or derivative thereof can be present at a con 0003. The disclosures of each patent, patent application, centration of 10 ng/ml to 100 ug/ml. The B-defensin 2 and publication cited or described in this document are polypeptide or derivative thereof can be present at a con hereby incorporated herein by reference, in their entireties. centration of 0.00001 to 50% by weight. 0016. The invention also features compositions compris 0004 Use of antimicrobial substances in compositions ing at least one B-defensin 3 polypeptide having SEQ ID Such as cosmetics, pharmaceutical products, washing and/or NO:4 or 5, or a derivative thereof. In some aspects, the cleaning agents, as well as water-treatment agents and B-defensin 3 polypeptide or derivative thereof is present at cooling lubricants, is known at the state of the art. a concentration of 0.00001 to 50% by weight. 0005 If these antimicrobial substances come into contact 0017. The inventive compositions can further comprise at with human skin in particular, that is usually linked with least one deodorizing agent or antiperspirant, at least one poor tolerance by the skin or undesired skin reactions. Such sebum regulator, at least one anti-inflammatory agent, and/ as irritations, reddenings, and sensitization reactions. or at least one prebiotic agent. 0006 Body odor, for instance, arises from the degrada 0018. Also featured are methods for reducing or prevent tion of constituents of perspiration by bacteria of the skin ing microbial contamination of washing agents, cleaning flora. It is also known that many antibacterial agents have agents, cosmetics, pharmaceuticals, filter media, construc poor action against body odor. tion materials, or water treatment agents. The methods 0007 Microbial activity is the cause, or a significant generally comprise admixing an effective amount of any one factor in, development of bad skin or pimples as well as or combination of the inventive compositions described and dandruff. exemplified herein with the washing agents, cleaning agents, cosmetics, pharmaceuticals, filter media, construction mate 0008 Use of antimicrobial agents in cosmetic and/or rials, or water treatment agents. In some aspects, the cos pharmaceutical preparations can, among other things, metics are deodorants, dental care agents, or oral care reduce dandruff, reduce body odor, improve the status of bad agents. In some aspects, the water treatment agents are used skin, and protect from, or treat, infections, particularly of to treat water in closed-loop circulation, or to treat water that sensitive and/or irritated skin. is used as a cooling lubricant. 0009 If the antimicrobial agents are used in cosmetic preparations, they usually act unselectively on the organisms 0019. Also featured are methods for reducing growth of microbes on the skin, which microbes are harmful to the in the skin flora and inhibit not only the harmful microor skin. The methods generally comprise administering to the ganisms on the skin, but also the useful ones (especially in skin an effective amount of the inventive compositions in the face, on the head skin, and under the armpits). combination with at least one prebiotically active agent. In 0010 This destruction of the skin flora often results in a Some aspects, the prebiotically active agent is a plant extract, possible short-term improvement of the corresponding sta glycerol monoalkyl ether, or ester of an organic acid. In tus of the skin followed, after terminating the treatment, by Some aspects, the microbes are coagulase-positive Staphy a reestablishment of the equilibrium of the various skin lococcus spp., Propionibacterium acnes, Candida albicans, microorganisms, which can sometimes be shifted toward Malassezia furfur, Corynebacterium spp. or Peptostrepto increased occurrence of pathogenic/harmful microorgan coccus spp. The Staphylococcus spp. can be Staphylococcus 1SS. Ca,S. US 2008/0050398 A1 Feb. 28, 2008 0020. The invention also features methods for reducing 0032. Furthermore, circulating water systems, for water the growth of microbes that are harmful to the mouth, treatment, or cooling lubricant systems, are often affected by comprising exposing the mouth or a dental prosthesis to an bacterial contaminants (frequently by bacteria of the genus effective amount of the inventive compositions in combina Pseudomonas and/or other aqueous microorganisms) which tion with at least one prebiotically active agent as described should be attacked by adding antimicrobial agents to the and exemplified herein. cooling lubricant or water-treatment agent in question. 0033. Therefore it is a further objective of the present DETAILED DESCRIPTION OF ILLUSTRATIVE invention to provide new antimicrobially active cooling EMBODIMENTS lubricants and/or water-treatment agents that comprise 0021. By use of molecular biology methods, the follow intentionally effective antimicrobial agents. ing characteristics were found according to the invention to 0034. These objectives are attained by compositions con be typical of persons with strong body odor: taining at least one peptide having a structure or structural 0022) a) reduced proportion of Staphylococcus epidermi pattern of B-defensin 2 according to SEQ ID NO: 1 and/or dis its derivatives, in which X is selected independently from the group of the essential and nonessential amino acids, 0023 b) increased proportion of Staphylococcus hominis especially human B-defensin 2. 0024 c) slightly increased proportion of Anaerococcus 0035. The defensins are antimicrobial peptides with short Octavius chain length (10 to 50 amino acids) which have been found in, among other places, epithelial tissue of both humans and 0.025 d) slightly increased proportion of Corynebacte animals. rium species. 0036). In humans, the B-defensins occur primarily in the 0026. Thus there is a need for substances that shift the mucous membranes and epithelial cells, especially in or on microflora profile of strong-smelling Subjects or of Subjects the skin. Human B-defensin 1 (hBD1) is found predomi with unpleasant body odor toward the microflora profile of nantly in the kidneys, saliva, lungs and skin, while human weakly-smelling Subjects, especially odor-neutral Staphylo B-defensin 2 (hbd2) is expressed primarily in the skin, the cocci, promote S. epidermidis in particular, and simulta trachea and the lungs if there is a bacterial stimulus. neously prevent growth of odor-forming Staphylocci, espe 0037 According to the invention "peptides having a cially of S.