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Agent for Expelling Parasites in Humans, Animals Or Birds

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Agent for Expelling Parasites in Humans, Animals Or Birds (19) TZZ Z_T (11) EP 2 496 089 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A01N 65/00 (2009.01) A01N 65/10 (2009.01) 22.02.2017 Bulletin 2017/08 A61K 36/23 (2006.01) A01P 5/00 (2006.01) (21) Application number: 10803029.7 (86) International application number: PCT/BE2010/000077 (22) Date of filing: 05.11.2010 (87) International publication number: WO 2011/054066 (12.05.2011 Gazette 2011/19) (54) AGENT FOR EXPELLING PARASITES IN HUMANS, ANIMALS OR BIRDS MITTEL ZUR ABWEISUNG VON PARASITEN BEI MENSCHEN, TIEREN ODER VÖGELN AGENT POUR EXPULSER DES PARASITES CHEZ DES HUMAINS, DES ANIMAUX OU DES OISEAUX (84) Designated Contracting States: (56) References cited: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB • RAMADAN NASHWA I ET AL: "The in vitro effect GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO of assafoetida on Trichomonas vaginalis", PL PT RO RS SE SI SK SM TR JOURNAL OF THE EGYPTIAN SOCIETY OF PARASITOLOGY, EGYPTIAN SOCIETY OF (30) Priority: 06.11.2009 BE 200900689 PARAS1TOLOGY, CAIRO, EG, vol. 33, no. 2, 1 August 2003 (2003-08-01) , pages 615-630, (43) Date of publication of application: XP009136264, ISSN: 1110-0583 12.09.2012 Bulletin 2012/37 • DATABASE MEDLINE [Online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, (73) Proprietors: US; December 2004 (2004-12), RAMADAN • MEIJS, Maria Wilhelmina NASHWA I ET AL: "Effect of Ferula assafoetida 4852 Hombourg (BE) on experimental murine Schistosoma mansoni • VAESSEN, Jan Jozef infection.", XP002592455, Database accession 4852 Hombourg (BE) no. NLM15658063 & JOURNAL OF THE EGYPTIAN SOCIETY OF PARASITOLOGY DEC (72) Inventors: 2004 LNKD- PUBMED:15658063, vol. 34, no. 3 • MEIJS, Maria Wilhelmina Suppl, December 2004 (2004-12), pages 4852 Hombourg (BE) 1077-1094, ISSN: 0253-5890 • VAESSEN, Jan Jozef • NAGAICH SHALINI ET AL: "Anthelmintic efficacy 4852 Hombourg (BE) of the aqueous extract of Ferula asafoetida (Vern. Heing) against common poultry worms Ascaridia (74) Representative: Habets, Winand galli and Heterakis gallinae", JOURNAL OF Life Science Patents PARASITOLOGY AND APPLIED ANIMAL PO Box 5096 BIOLOGY, IN, vol. 10, no. 1-2, 1 January 2001 6130 PB Sittard (NL) (2001-01-01), pages 83-88, XP009136275, ISSN: 0971-2208 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 496 089 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 496 089 B1 • FAROOQ Z ET AL: "Ethnoveterinary practices for • BLANCOU J ET AL: "Historical and anecdotal the treatment of parasitic diseases in livestock in activity regarding ancient plant therapy of Cholistan desert (Pakistan)", JOURNAL OF infectious and parasitic animal diseases", ETHNOPHARMACOLOGY, ELSEVIER PHYTOTHÉRAPIE ; DE LA RECHERCHE À LA SCIENTIFIC PUBLISHERS LTD, IE LNKD- PRATIQUE, SPRINGER-VERLAG, PA LNKD- DOI:10.1016/J.JEP.2008.03.015, vol. 118, no. 2, 23 DOI:10.1007/S10298-006-0155-9, vol. 4, no. 2, 1 July 2008 (2008-07-23) , pages 213-219, June 2006 (2006-06-01), pages 74-82, XP022758508, ISSN: 0378-8741 [retrieved on XP019388186, ISSN: 1765-2847 2008-03-29] • KUMAR P ET AL: "Molluscicidal activity of Ferula • JABBAR A ET AL: "An inventory of the asafoetida, Syzygium aromaticum and Carum ethnobotanicals used as anthelmintics in the carvi and their active components against the southern Punjab (Pakistan)", JOURNAL OF snail Lymnaea acuminata", CHEMOSPHERE, ETHNOPHARMACOLOGY, ELSEVIER PERGAMON PRESS, OXFORD, GB LNKD- SCIENTIFIC PUBLISHERS LTD, IE LNKD- DOI:10.1016/J.CHEMOSPHERE.2005.08.071, vol. DOI:10.1016/J.JEP.2006.04.015, vol. 108, no. 1, 3 63, no. 9, 1 June 2006 (2006-06-01), pages November 2006 (2006-11-03), pages 152-154, 1568-1574, XP025041818, ISSN: 0045-6535 XP025085984, ISSN: 0378-8741 [retrieved on [retrieved on 2006-06-01] 2006-11-03] • MRADU GUPTA 1 ET AL: "Therapeutic utilization Remarks: of secretory products of some", INDIAN Thefile contains technical information submitted after JOURNAL OF TRADITIONAL KNOWLEDGE, the application was filed and not included in this RESOURCES, NEW DELHI, NEW DELHI - INDIA, specification vol. 5, no. 4, 1 October 2006 (2006-10-01) , pages 569-575, XP018021472, ISSN: 0972-5938 2 EP 2 496 089 B1 Description [0001] The present description relates to a substance which can be used for expelling and preventing the occurrence of parasites, from humans, mammals or birds. 5 [0002] Parasites are life-forms which sustain themselves and reproduce at the expense of another organism, the host. They compriseendoparasites and ectoparasites. Parasitic wormsor helminthswhich live inside their host feed themselves via the living host and in this way gain protection while the food absorption of the host is impaired, whereby it becomes weak and ill. The consequences of parasite infections are generally known. They cause gastroenteritis, diarrhoea, serious weight loss, colic and other disorders, sometimes resulting in death. 10 [0003] The endoparasites comprise parasites living inside the gastrointestinal, or in other organs, such as liver, and lungs. Ectoparasites live on the surface of the host. They occur in humans as well as animals. Parasitic worms include the platyhelminths or flatworms, to which the cestodes or the tapeworms and the trematodes, such as liver fluke, belong, and the nematodes or the roundworms. Cestodes are segmented flatworms, trematodes are unsegmented flatworms and nematodes are cylindrical worms. 15 [0004] Other types of parasites that live inside the gastrointestinal tract are parasitic arthropods such as larvae of flies and mites, and protozoa. A large number of anthelmintics are already commercially available. However, the helminths develop an increasing resistance to most of the known anthelmintics. Resistance is highly disadvantageous since it results in the reduction of reproduction in livestock, other mammals and birds, and additionally results in a threat to the success of present treatment. 20 [0005] There are various causes for the occurrence of t resistances. Resistance can inter alia occur due to changes in genes or in gene expressions, whereby the medicine can react or be modified, resulting in the loss of the activity and the survival of the helminths. [0006] Resistance mechanisms can also occur due to the involvement of transport proteins which remove the medicines such that the medicine can no longer reach their target. 25 [0007] There are several reasons which lead to these resistance mechanisms. This can be due to a treatment frequency which is too high, repetitive use of the same medication regimes, or under dosing the anthelmintics. Public health authorities rely increasingly on mass medication administration programs to control parasites in both humans and animals such as livestock. They are however aware that resistance to medication can always increase and are searching for other options. In the Netherlands for instance a chemical anthelminthic for horses is still available only on veterinary 30 prescription. The purpose here is to avoid excessive use and to avoid the occurrence of faster increasing resistance. In addition, the amount of antiparasitic medicines on the market is limited, and only a small number of new medicines are being developed. [0008] For each chemical class of anthelmintics (imidothiazole, benzimidazole, macrocyclic lactones and others) it is the case that a resistance to one type of medicine generally brings about resistance to other types. It is possible, and 35 is also an increasingly frequent occurrence, that there are multiple resistances wherein parasites develop sequential resistance, this irrespective of determined classes of anthelmintics. Furthermore, once a parasite is resistant to a de- termined population of medicines, it has never yet been the case that this population loses its resistance. When an anthelmintic class is first administered, there are only a few resistance alleles. This indicates that, if there is no treatmen t, resistance alleles carry with them neutral or negative reproduction fitness. Resistance is moreover an inevitable conse- 40 quence of the use of medicines and the selection for resistance would depend on the relative reproduction rate assigned to the susceptibility of resistance alleles to a determined level of use of medicines. [0009] For specific parasites and in specific situations of medicine use it may be that resistance never develops. When resistance to a medicine occurs, there are three stages linked to the accumulation of resistance alleles: 45 1. Resistance is generally a random event influenced by the population size and diversity; mutation rate of the genes; and the relative condition of those individuals having the mutation compared to the wild-type gene. The frequency of the resistance allele is in general fairly low. 2. The development of the resistance occurs as a response to a selective agent which kills susceptible worms but which allows those which are resistant to survive and reproduce. Treatment with the medicines is therefore a very 50 potent means for selecting resistance alleles. If continuous selection takes place, the frequency of the resistance alleles then increases and these are spread through the population. 3. Resistance develops as soon as the selection increases progressively and increasing numbers of R-alleles occur. From this moment the parasite is found to have become resistant. 55 [0010] The presence of resistant genotypes always occurs much faster than clinical resistance can be observed. Since the medicines are very often used in a dosage which is much higher than the minimum required to kill most of the worms, the selection can produce a high frequency of R-alleles before clinical resistance is observed.
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