Europäisches Patentamt *EP001212093B1* (19) European Patent Office Office européen des brevets (11) EP 1 212 093 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: A61K 47/44, A61K 35/74, of the grant of the patent: A61P 31/02, A61P 17/00 07.07.2004 Bulletin 2004/28 (86) International application number: (21) Application number: 00964921.1 PCT/US2000/023448 (22) Date of filing: 25.08.2000 (87) International publication number: WO 2001/013956 (01.03.2001 Gazette 2001/09) (54) USE OF EMU OIL AS A CARRIER FOR ANTIFUNGAL, ANTIBACTERIAL AND ANTIVIRAL MEDICATIONS VERWENDUNG VON EMU-ÖL ALS TRÄGER FÜR FUNGIZIDE, ANTIBAKTERIELLE UND ANTIVIRALE ARZNEIEN UTILISATION D’HUILE D’EMEU ET DE SES DIVERSES FRACTIONS COMME EXCIPIENT POUR DES MEDICAMENTS ET DES PREPARATIONS ANTIFONGIQUES, ANTIBACTERIENNES ET ANTIVIRALES (84) Designated Contracting States: (56) References cited: AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU WO-A-98/47374 US-A- 5 472 713 MC NL PT SE US-A- 5 744 128 US-A- 5 849 334 US-A- 6 103 246 (30) Priority: 26.08.1999 US 384043 • ZEMTSOV A ET AL: "Moisturizing and cosmetic (43) Date of publication of application: properties of emu oil: Apilot double blind study" 12.06.2002 Bulletin 2002/24 AUSTRALASIAN JOURNAL OF DERMATOLOGY, vol. 37, no. 3, 1996, pages (73) Proprietor: Ganeden Biotech, Inc. 159-162, XP000982121 San Diego, CA 92121 (US) • WHITEHOUSE M W ET AL: "Emu Oil(s): A source of non-toxic transdermal anti-inflammatory (72) Inventor: FARMER, Sean agents in aboriginal medicine" San Diego, CA 92115 (US) INFLAMMOPHARCOLOGY, vol. 6, 1998, page 1-8 XP000982183 (74) Representative: Jump, Timothy John Simon et al • HODGES C F ET AL: "Potential biocontrol of Venner Shipley & Co. Sclerotina homeocarpa and Bipolaris 20 Little Britain sorokiniana on the phylloplane of Poa pratensis London EC1A 7DH (GB) with strains of Pseudomonas sp." PLANT PATHOLOGY, vol. 43, no. 3, 1994, pages 500-506, XP000982028 Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 212 093 B1 Printed by Jouve, 75001 PARIS (FR) EP 1 212 093 B1 Description FIELD OF THE INVENTION 5 [0001] The present invention relates to compositions and methods of use for the treatment of bacterial, fungal, and viral infections of the dermis and cuticle. More specifically, the present invention relates to compositions and methods of use of Emu Oil, and it various associated fractions, in combination with the appropriate medicaments, in the treatment of bacterial, fungal, and viral infections of the dermis and cuticle. More specifically, the present invention relates to the utilization of therapeutic compositions comprised of Emu Oil in combination with one or more of the following: a lactic 10 acid-producing vegetative bacteria or spores thereof, an extracellular product derived from said lactic acid-producing bacterial strain, and an anti-microbial agent, as a topical composition for the prevention and/or control of infections caused by bacterium, fungi, yeast, and virus, and combinations thereof. BACKGROUND OF THE INVENTION 15 1. Emu Oil [0002] Emu Oil, is an animal-derived lipid composition, extracted from the Emu (Dromais Novae-Hollandiae), a flight- less bird part of a group called ratites (which also includes the ostrich and the kiwi), indigenous to Australia and New 20 Zealand. [0003] Emu Oil is extracted from a thick fat-pad on the back of the bird which putatively functions to protect the animal from the extreme temperatures in its Australian homeland. The fat is carefully extracted to prevent the formation of trans-fatty acids, wherein approximately 100 pounds of fat produces approximately 50 to 90 pounds of unrefined, pale yellow oil. The chemical composition and characteristics of Emu Oil has been quantitatively ascertained and is set forth 25 below in Table I. Table I Fatty Acid Composition: 30 C-14:0 (Myristic): 0.4% C-16:0 (Palmitic): 21.5% C-16:1 (Palmitoleic): 3.7% C-18:0 (Stearic): 10.6% C-18:1 (Oleic): 51.4% 35 C-18:2 (Linoleic): 12.7% C-18:3 (Linolenic): 0.9% Calculated Iodine Value: 69.7 Free Fatty Acid: 0.33% 40 Acid Value: 0.66% Peroxide Value: 1.53% Moisture: 0.03% Refractive Index @ 40°C: 1.4606% 45 [0004] As illustrated in Table I, when correctly extracted and processed, Emu Oil is comprised of approximately 50% to 70% monounsaturated fatty acids, with the rest being both saturated and polyunsaturated fatty acids (see, e.g., American Emu Association News, March 1995). Emu Oil is almost purely triglyceride in nature, which makes it an almost completely neutral lipid. In addition, the monounsaturated fatty acid, oleic acid, is the largest single fatty acid component of Emu Oil. Traditional beliefs of geographically widely-separated Australian Aboriginal communities agree 50 on the beneficial properties of Emu Oil as a natural remedy. The oral history of the Australian Aborigines indicates their use of Emu Oil for over forty thousand years to reduce pain and stiffness in sore muscles and joints, to help expedite wound healing, as a dermal protectorate from the effects of wind and sun, and in the treatment of bruised subcutaneous tissue, bums and dry skin problems. Methods of administration are quire varied. For example, Aborigines have revealed methods of treatment which included hanging an Emu skin on a tree to collect the oil, and wrapping the affected area 55 on the individual in a freshly- killed Emu skin. However, it is believed that in both of the aforementioned scenarios, the catalyst of the suns' heat was used to liquefy the Emu fat and enhance its absorption qualities. [0005] Documented records of the utilization of Emu Oil may be antedated well over 100 years (see, e.g., Whitehouse, 2 EP 1 212 093 B1 et al., 1996. Concerning Emu Oil and its anti-arthritic activity. Fifth Queensland Poultry Science Symposium, Gatton College). The use of Emu Oil was among many natural remedies adopted by settlers from the original inhabitants of Australia. The first report known was published in the Australian Post regarding experiments by Dr. Peter Gosh (Ray- mond Purves Bone and Joint Research Laboratories, University of Sydney at the Royal North Shore Hospital) and Dr. 5 Michael Whitehouse (Department of Pathology, University of Adelaide), wherein the Emu Oil was required to be mas- saged vigorously onto the sore muscle or joint and the process repeated as often as required, hence pressure, heat and duration of rubbing were all deemed to be relevant factors. [0006] This, although Emu Oil has been previously described, the majority of its uses or properties/characteristics is anecdotal in nature. These uses and properties include (see, e.g., DuBois, 1999. Explore Issue 8:1-10): (i) its ability 10 to act as a dermal penetrant and medicament carrier; (ii) its anti-inflammatory properties; (iii) its ability to act as an emollient/emulsifier; (iv) its bacteriostatic properties; (v) its low potential for irritation of the skin; (vi) its non-comedogenic properties (i.e., it does not clog up pores); and (vii) its moisturizing, wound-healing, general "anti-aging" properties. However, the quan- titative information currently available almost exclusively relates to the benefits of Emu Oil as an anti-inflammatory 15 agent for arthritis, its uses for cardiovascular health when ingested, which is similar to the use of Omega-3 fish oils to improve high-density lipoprotein (HDL) cholesterol, and its moisturizing and general "anti-aging" properties. [0007] There is much anecdotal material available on the anti-inflammatory abilities of Emu Oil. It has been shown to reduce pain, swelling and stiffness in joints, to reduce recent bruising and muscle pain, and ease sports related muscle strains as well. Studies have shown that different Emu Oils (i.e., oils which were extracted by different meth- 20 odologies, from different sources, and the like) possessed different levels of anti-inflammatory ability. The ability of Emu Oil to penetrate the stratum corneum dermal barrier and concomitantly act as a carrier, makes it highly valuable for use in therapeutic compounds in the prevention and/or treatment of a variety of conditions. This ability is believed to be primarily due to both its extremely high content of oleic acid and a total lack of indigenous phospholipids. Ac- cordingly, Emu Oil could be combined with various medicinals or cosmetic materials to facilitate their ability to penetrate 25 this layer of keritinized tissue in a more efficacious and cost-effective manner than the currently-utilized liposome- and iontophorisis-based technologies. For example, the ability of Emu Oil to act as a trans-dermal penetrant with respect to Ketoprofen, a well known non-steroidal, anti-inflammatory drug (NSAID) found in Actron™ and like products, was examined in a recent study performed at Auburn University. Ketoprofen is one of the proprionic acid derivative drugs, which have been utilized in numerous European countries for more than 15 years as an effective treatment for rheu- 30 matoid arthritis and osteoarthritis. Although it is available in more than 80 countries throughout the world, it did not receive approval for over-the-counter (OTC) use in the United States until 1996. Although Ketoprofen is readily ab- sorbed, it frequently produces a number of adverse side-effects in the gastrointestinal tract when taken orally.