Anthelmintics and Their Application in Veterinary Medicine
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(12) United States Patent (10) Patent No.: US 8,227,427 B2 Coracci Neto Et Al
USOO8227427B2 (12) United States Patent (10) Patent No.: US 8,227,427 B2 Coracci Neto et al. (45) Date of Patent: Jul. 24, 2012 (54) VETERINARIAN COMPOSITION (52) US. Cl. ........................................ .. 514/27; 514/368 COMPRISING AN ORGANIC SALT 0F (58) Field of Classi?cation Search ................. .. 513/71; LEVAMISOLE IN COMBINATION WITH AT 548/155; 514/27, 368 LEAST ONE AVERMECTIN AND/OR See application ?le for complete search history. MILBEMYCIN (75) Inventors: Dolivar Coracci Neto, Sertaozinho (56) References Cited (BR); Nelson Henriques Fernandes Filho, Jaboticabal (BR); Ricardo da FOREIGN PATENT DOCUMENTS Silva Sercheli, Jaboticabal (BR) BR PI0505716 A 9/2007 GB 2150024 A 6/1985 (73) Assignee: NPA—Nucleo de Pesquisas Aplicadas WO 00/74489 A1 12/2000 Ltda., Jaboticabal (BR) WO 2004/009080 A1 1/2004 OTHER PUBLICATIONS ( * ) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 International Search Report. U.S.C. 154(b) by 575 days. Analytical Report Characterization of Pharmaceutical Input Aurixazol (Feb. 20, 2010). (21) App1.No.: 12/097,683 Primary Examiner * Elli Peselev (22) PCT Filed: Dec. 18, 2006 (74) Attorney, Agent, or Firm * Laurence P. Colton; Smith Risley Tempel Santos LLC (86) PCT No.: PCT/BR2006/000282 § 371 (0X1)’ (57) ABSTRACT (2), (4) Date: Nov. 3, 2008 Veterinarian composition comprising an organic salt of (87) PCT Pub. No.: WO2007/068073 levamisole in combination With at least one avermectin and/ or milbemycin. A veterinarian formulation comprising of organ PCT Pub. Date: Jun. 21, 2007 ics salts of levamisole, more speci?cally to the levamisole salt of 2,6-diiodo-4-nitrophenol and the levamisole salt of 4-hy (65) Prior Publication Data droxy-3-iodo-5-nitrobenzonitrile With avermectins and mil US 2009/0075918 A1 Mar. -
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DISEASES OF AQUATIC ORGANISMS Published July 30 Dis Aquat Org Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. 11: Gyrodactylus sp. J. L. Tojo*, M. T. Santamarina Department of Microbiology and Parasitology, Laboratory of Parasitology, Faculty of Pharmacy, Universidad de Santiago de Compostela, E-15706 Santiago de Compostela, Spain ABSTRACT: A total of 24 drugs were evaluated as regards their efficacy for oral treatment of gyro- dactylosis in rainbow trout Oncorhj~nchusmykiss. In preliminary trials, all drugs were supplied to infected fish at 40 g per kg of feed for 10 d. Twenty-two of the drugs tested (aminosidine, amprolium, benznidazole, b~thionol,chloroquine, diethylcarbamazine, flubendazole, levamisole, mebendazole, n~etronidazole,mclosamide, nitroxynil, oxibendazole, parbendazole, piperazine, praziquantel, roni- dazole, secnidazole, tetramisole, thiophanate, toltrazuril and trichlorfon) were ineffective Triclabenda- zole and nitroscanate completely eliminated the infection. Triclabendazole was effective only at the screening dosage (40 g per kg of feed for 10 d), while nitroscanate was effective at dosages as low as 0.6 g per kg of feed for 1 d. KEY WORDS: Gyrodactylosis . Rainbow trout Treatment. Drugs INTRODUCTION to the hooks of the opisthohaptor or to ulceration as a result of feeding by the parasite. The latter is the most The monogenean genus Gyrodactylus is widespread, serious. though some individual species have a restricted distri- Transmission takes place largely as a result of direct bution. Gyrodactyloses affect numerous freshwater contact between live fishes, though other pathways species including salmonids, cyprinids and ornamen- (contact between a live fish and a dead fish, or with tal fishes, as well as marine fishes including gadids, free-living parasites present in the substrate, or with pleuronectids and gobiids. -
Witola, Basis of Anthelmintic Resistance and Development Of
9/8/2016 Basis of Anthelmintic Resistance and Novel Approaches to Development of New Efficacious Anthelmintic Drugs William H. Witola, BVetMed, MSc., Ph.D. Department of Pathobiology College of Veterinary Medicine University of Illinois at Urbana-Champaign E-mail: [email protected] Current Anthelmintics 3 Classes of anthelmintic drugs registered in the USA : 1.) Benzimidazoles • Fenbendazole, Safeguard, Panacur 2.) Macrocyclic Lactones • Avermectins: Ivermectin, Ivomec, Primectin, Privermectin • Eprinomectin: Eprinex • Doramectin: Dectomax • Milbimycins: Moxidectin, Cydectin, Quest 3.) Nicotinic Agonists • Imidothiazoles: Levamisole, Prohibit • Tetrahydropyrimidines: Morantel, Rumatel, Positive Goat Pellet, Goat dewormer, Pyrantel, Strongid Spiroindoles (Not registered in US) Amino-acetonitriles (Not registered in US ) How do anthelmintic drugs kill parasites? • Benzimidazoles (Valbazen, Safeguard): Bind to a parasite protein called β-tubulin leading to collapse of parasite skeleton structure. • Avermectin/Milbemycins (Ivomec, cydectin): Bind to proteins in throat (pharynx) of parasite leading to paralysis – parasite can’t eat anymore & dies of starvation! • Imidazothiazoles/Tetrahydropyrimidine (Levamisole, Pyrantel, Morantel): bind to acetylcholine receptors causing muscle paralysis. 1 9/8/2016 Status of Anthelmintics Efficacy Drug Host First 1st Report of Approved Resistance Benzimidazoles : Thiabendazole, Albendazole Sheep, 1961 1964 goat, Horse, 1962 1965 Imidothiazoles-tetrahydropyrimidines : Levamisole, Sheep 1970 1979 Pyrantel -
Comparative Efficacies of Commercially Available Benzimidazoles Against Pseudodactylogyrus Infestations in Eels
DISEASES OF AQUATIC ORGANISMS Published October 4 Dis. aquat. Org. l Comparative efficacies of commercially available benzimidazoles against Pseudodactylogyrus infestations in eels ' Department of Fish Diseases, Royal Veterinary and Agricultural University, 13 Biilowsvej, DK-1870 Frederiksberg C, Denmark Department of Pharmacy, Royal Veterinary and Agricultural University, 13 Biilowsvej. DK-1870 Frederiksberg C,Denmark ABSTRACT: The antiparasitic efficacies of 9 benzimidazoles in commercially avalable formulations were tested (water bath treatments) on small pigmented eels Anguilla anguilla, expenmentally infected by 30 to 140 specimens of Pseudodactylogyrus spp. (Monogenea).Exposure time was 24 h and eels were examined 4 to 5 d post treatment. Mebendazole (Vermox; 1 mg 1-') eradicated all parasites, whereas luxabendazole (pure substance) and albendazole (Valbazen) were 100 % effective only at a concen- tration of 10 mg I-'. Flubendazole (Flubenol), fenbendazole (Panacur) and oxibendazole (Lodltac) (10 mg l-') caused a reduction of the infection level to a larger extent than did triclabendazole (Fasinex) and parbendazole (Helmatac).Thiabendazole (Equizole), even at a concentration as high as 100 mg l-', was without effect on Pseudodactylogyrus spp. INTRODUCTION range of commercially available benzimidazole com- pounds. If drug resistance will develop under practical The broad spectrum anthelmintic drug mebendazoIe eel-farm conditions in the future, it is likely to be was reported as an efficacious compound against infes- recognized during treatments with commercially avail- tations of the European eel Anguilla anguilla with gill able drug formulations. Therefore this type of drug parasitic monogeneans of the genus Pseudodactylo- preparations were used in the present study. gyms (Szekely & Molnar 1987, Buchmann & Bjerre- gaard 1989, 1990, Mellergaard 1989). -
Bulletin Leading the Fight Against Heartworm Disease
BULLETIN LEADING THE FIGHT AGAINST HEARTWORM DISEASE SEPTEMBER HEARTWORM 2017 Q&A VOLUME 44 No. 3 Heartworm History: In What Year Was Heartworm First INSIDE THIS ISSUE Treated? Page 4 From the President Page 8 Research Update Abstracts from the Literature Page 14 Heartworm Hotline: Role of Heat Treatment in Diagnostics Page 19 NEW! Best Practices: Minimizing Heartworm Transmission in Relocated Dogs uestions from members, prac- published in the 1998 AHS Symposium 1 titioners, technicians, and the Proceedings. Dr. Roncalli wrote, “The Page 21 Qgeneral public are often submit- first trial to assess the efficacy of a Welcome Our New AHS ted to the American Heartworm Society microfilaricide (natrium antimonyl tar- Student Liaisons (AHS) via our website. Two of our AHS trate) was conducted some 70 years Board members, Dr. John W.McCall and ago (1927) in Japan by S. Itagaki and R. Page 25 Dr. Tom Nelson, provided the resources Makino.2 Fuadin (stibophen), a trivalent In the News: Surgeons to answer this question: In What Year antimony compound, was tested, intra- Remove a Heartworm from Was Heartworm First Treated? venously, as a microfilaricide by Popescu the Femoral Artery of a Cat The first efforts to treat canine heart- in 1933 in Romania and by W.H. Wright worm disease date back to the 1920s. Dr. and P.C. Underwood in 1934 in the USA. Page 26 Nelson referenced a review article by Dr. In 1949, I.C. Mark evaluated its use Quarterly Update Raffaele Roncalli, “Tracing the History of intraperitoneally.” What’s New From AHS? Heartworms: A 400 Year Perspective,” Continues on page 7 American Heartworm Society / PO Box 8266, Wilmington, DE 19803-8266 Become an American Heartworm Society www.heartwormsociety.org / [email protected] fan on Facebook! Follow us on Twitter! OUR GENEROUS SPONSORS PLATINUM LEVEL PO Box 8266 Wilmington, DE 19803-8266 [email protected] www.heartwormsociety.org Mission Statement The mission of the American Heartworm Society is to lead the vet- erinary profession and the public in the understanding of heartworm disease. -
Skin Probiotics ACCELERATING INNOVATION
ACCELERATING INNOVATION James Madison University technologies are available for licensing through its nonprofit affiliate, James Madison Innovations, Inc. Skin Probiotics Inventors: Reid Harris and Kevin Minbiole Department: Biology and Chemistry Overview Research Funding and Source: National Science Foundation James Madison University inventors have filed a patent Years of Development: 4 years application on a helpful bacterium that could potentially be Technology Readiness: Research Development used as a therapy for human skin fungus such as athlete’s foot. Patent Status: U.S. patent pending 20110002891 The JMU inventors have developed a potential process to Contact: Mary Lou Bourne, Director of Technology Transfer deliver a helpful microbe, Janthinobacterium Lividum to the James Madison University skin using a pharmaceutically acceptable carrier. The microbe Phone: (540)568-2865 E-mail: [email protected] has been shown to suppress bacterial and fungal growth on animals and in lab demonstrations. Tech Transfer and Business Model Infections can be a problem for a wide array of hosts. For JMI is interested in identifying an existing company or example, there are a variety of infections, such as bacterial, entrepreneur interested in commercializing the technology viral and/or fungal infections, that affect a large percentage of either under an exclusive or a non-exclusive license. A the human population. Tricophyton rubrum, the fungus that small company or entrepreneur could further develop the causes athlete’s foot, is responsible for approximately 46% to technology, possibly using SBIR or STTR funding. 72% of cutaneous and nail mycoses worldwide. Onychomycosis, a common and persistent fungal infection, is Market and Competition In 2008, the U.S. -
Computational Studies of Drug Repurposing Targeting P-Glycoprotein Mediated Multidrug-Resistance Phenotypes in Agents of Neglect
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.12.147926; this version posted June 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Computational studies of drug repurposing targeting P- glycoprotein mediated multidrug-resistance phenotypes in agents of neglected tropical diseases Nivedita Jaishankar 1, Sangeetha Muthamilselvan 2, Ashok Palaniappan 1,2* 1 Department of Biotechnology, Sri Venkateswara College of Engineering, Post Bag No. 1, Pennalur, Sriperumbudur Tk 602117. India 2 Department of Bioinformatics, School of Chemical and BioTechnology, SASTRA Deemed University, Thanjavur 613401. India * Corresponding author: [email protected] ABSTRACT Mammalian ABCB1 P-glycoprotein is an ATP- dependent efflux pump with broad substrate specificity associated with cellular drug resistance. Homologous to this role in mammalian biology, the P-glycoprotein of agents of neglected tropical diseases (NTDs) mediates the emergence of multidrug- resistance phenotypes. The clinical and socioeconomic implications of NTDs are exacerbated by the lack of research interest among Big Pharma for treating such conditions. This work aims to characterise P-gp homologues in certain agents of key NTDs, namely (1) Protozoa: Leishmania major, Trypanosoma cruzi; (2) Helminths: Onchocerca volvulus, Schistosoma mansoni. PSI-BLAST searches against the genome of each of these organisms confirmed the presence of P-gp homologues. Each homologue was aligned against five P- gp sequences of known structure, to identify the most suitable template based on sequence homology, phylogenetic nearest neighbor, and query coverage. -
Chemotherapy of Gastrointestinal Helminths
Chemotherapy of Gastrointestinal Helminths Contributors J. H. Arundel • J. H. Boersema • C. F. A. Bruyning • J. H. Cross A. Davis • A. De Muynck • P. G. Janssens • W. S. Kammerer IF. Michel • M.H. Mirck • M.D. Rickard F. Rochette M. M. H. Sewell • H. Vanden Bossche Editors H. Vanden Bossche • D.Thienpont • P.G. Janssens UNIVERSITATS- BlfiUOTHElC Springer-Verlag Berlin Heidelberg New York Tokyo Contents CHAPTER 1 Introduction. A. DAVIS A. Pathogenic Mechanisms in Man 1 B. Modes of Transmission 2 C. Clinical Sequelae of Infection 3 D. Epidemiological Considerations 3 E. Chemotherapy 4 F. Conclusion 5 References 5 CHAPTER 2 Epidemiology of Gastrointestinal Helminths in Human Populations C. F. A. BRUYNING A. Introduction 7 B. Epidemiological or "Mathematical" Models and Control 8 C. Nematodes 11 I. Angiostrongylus costaricensis 11 II. Anisakis marina 12 III. Ascaris lumbricoides 14 IV. Capillaria philippinensis 21 V. Enterobius vermicularis 23 VI. Gnathostoma spinigerum 25 VII. Hookworms: Ancylostoma duodenale and Necator americanus . 26 VIII. Oesophagostoma spp 32 IX. Strongyloides stercoralis 33 X. Ternidens deminutus 34 XI. Trichinella spiralis 35 XII. Trichostrongylus spp 38 XIII. Trichuris trichiura 39 D. Trematodes 41 I. Echinostoma spp 41 II. Fasciolopsis buski 42 III. Gastrodiscoides hominis 44 IV. Heterophyes heterophyes 44 V. Metagonimus yokogawai 46 X Contents E. Cestodes 47 I. Diphyllobothrium latum 47 II. Dipylidium caninum 50 III. Hymenolepis diminuta 51 IV. Hymenolepis nana 52 V. Taenia saginata 54 VI. Taenia solium 57 VII. Cysticercosis cellulosae 58 References 60 CHAPTER 3 Epidemiology and Control of Gastrointestinal Helminths in Domestic Animals J. F. MICHEL. With 20 Figures A. Introduction 67 I. -
Veterinary Guide to Resistance & Parasites
Veterinary Guide to Resistance & Parasites How to make the Get Rotation Right deworming strategy part of your equine health wellness protocol. ||||||||||||||||||||||||||||||||||||||||| GET ROTATION RIGHT Resistant parasites – veterinary involvement is needed now. Deworming has come a long way in the past 50 years – from products that were nearly toxic and required complicated tubing to the easy-to-administer dewormers we know now. As more horse owners recognize the value of regular deworming, past troublemakers such as large strongyles have become much less of a threat. Still, deworming is nothing to take lightly. As internal parasites become more resistant, your expertise is needed Horseowners unknowingly more than ever to make sure deworming programs remain efficient contribute to resistance. and effective. Only with veterinary involvement will we control parasite • Rotating brand names, not populations, combat resistance and get rotation right. chemical classes – general confusion about when and RESISTANCE IS REAL: MULTIPLE DRUGS, MULTIPLE PARASITES. how to use different classes • No new drug class since avermectins in 1981. of dewormers. • Benzimidazole resistance in cyathostomes.1-3 • Lack of knowledge about • Pyrantel resistance in cyathostomes and ascarids.4-8,11 resistance issues. • Ivermectin and moxidectin resistance among ascarids.8,9,11 • Deworming many horses more • Early warning signs of macrocyclic-lactone-resistant cyathostomes.10 frequently than necessary. • Health-related issues caused by parasites: • Misunderstanding about the ~ Ascarids (roundworms) unique properties of larvicidal Verminous pneumonia: cough, nasal discharge, low-grade fever treatments and how to maximize Unthriftiness – rough hair coat their efficacy. Intestinal obstruction/colic • Underdosing their horses. Intestinal perforation leading to peracute death Decreased performance and reduced weight gain ~ Cyathostomes (small strongyles) Most common in young and old horses, but can afflict any horse. -
Natural Products As Potential Antiparasitic Drugs
Natural Products as potential antiparasitic drugs OLIVER KAYSER1, ALBRECHT F. KIDERLEN2, SIMON L. CROFT3 1Freie Universität Berlin Institut für Pharmazie, Pharmazeutische Biotechnologie Kelchstraße 31, 12169 Berlin, Germany 2Robert Koch-Institut Nordufer 20 13353 Berlin, Germany 3London School of Hygiene and Tropical Medicine Department of Infectious and Tropical Diseases Keppel Street London, WC1E 7HT, United Kingdom ABSTRACT: Pharmaceutical research in natural products represents a major strategy for discovering and developing new drugs. The use of medicinal plants for the treatment of parasitic diseases is well known and documented since ancient times e.g. by the use of Cinchona succiruba (Rubiaceae) as an antimalarial. This chapter provides a comprehensive review of the latest results in the field of antiparasitic drug development from biologic sources (plants, bacteria, fungi and marine organisms) focussing on the treatment of protozoal infections (Plasmodium, Leishmania, Trypanosoma spp.). The status of validated in vitro and in vivo assays is reviewed, discussing their different features, problems and limitations. Because of the high number of natural products tested against the aforesaid protozoa in the last years, we limit the discussion to lignans, phenolics, terpenoids, and alkaloids as defined natural product classes. The review also covers essential research topics of recent publications on specific natural products (e.g. licochalcone A, benzyl- and naphthylisoquinoline alkaloids, and artemisinin) and gives an outlook to semi- synthetic approaches of drugs already introduced in clinics or in clinical trial studies. 1. INTRODUCTION The fascination of natural products, mostly as used as a preparation from a plant with known medicinal properties, goes back to ancient times. The discovery of pure compounds as active principles in plants was first described at the beginning of the 19th century, and the art of exploiting natural products has become part of the molecular sciences. -
Anthelmintic Resistance of Ostertagia Ostertagi and Cooperia Oncophora to Macrocyclic Lactones in Cattle from the Western United States
Veterinary Parasitology 170 (2010) 224–229 Contents lists available at ScienceDirect Veterinary Parasitology journal homepage: www.elsevier.com/locate/vetpar Anthelmintic resistance of Ostertagia ostertagi and Cooperia oncophora to macrocyclic lactones in cattle from the western United States M.D. Edmonds, E.G. Johnson, J.D. Edmonds ∗ Johnson Research LLC, 24007 Highway 20-26, Parma, ID, 83660, USA article info abstract Article history: In June 2008, 122 yearling heifers with a history of anthelmintic resistance were obtained Received 15 October 2009 from pastures in northern California and transported to a dry lot facility in southwest- Received in revised form 28 January 2010 ern Idaho, USA. Fifty heifers with the highest fecal egg counts were selected for study Accepted 24 February 2010 enrollment. Candidates were equally randomized to treatment with either injectable iver- mectin (Ivomec®, Merial, 0.2 mg kg−1 BW), injectable moxidectin (Cydectin®, Fort Dodge, Keywords: 0.2 mg kg−1 BW), oral fenbendazole (Safe-Guard®, Intervet, 5.0 mg kg−1 BW), oral oxfenda- Anthelmintic resistance zole (Synanthic®, Fort Dodge, 4.5 mg kg−1 BW), or saline. At 14 days post-treatment, Cattle Bovine nematodes were recovered from the abomasum, small intestine, and large intestine. Par- Nematodes asitism was confirmed in the control group when 10/10 animals were infected with Efficacy adult Ostertagia ostertagi and 9/10 animals with both developing and early L4 stages of Cooperia O. ostertagi. Similarly, 9/10 animals were parasitized with adult Cooperia spp. Fenbenda- Ostertagia zole and oxfendazole efficacy verses controls were >90% against adult Cooperia spp., while moxidectin caused an 88% parasite reduction post-treatment (P < 0.05). -
Antiparasitic Properties of Cardiovascular Agents Against Human Intravascular Parasite Schistosoma Mansoni
pharmaceuticals Article Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni Raquel Porto 1, Ana C. Mengarda 1, Rayssa A. Cajas 1, Maria C. Salvadori 2 , Fernanda S. Teixeira 2 , Daniel D. R. Arcanjo 3 , Abolghasem Siyadatpanah 4, Maria de Lourdes Pereira 5 , Polrat Wilairatana 6,* and Josué de Moraes 1,* 1 Research Center for Neglected Diseases, Guarulhos University, Praça Tereza Cristina 229, São Paulo 07023-070, SP, Brazil; [email protected] (R.P.); [email protected] (A.C.M.); [email protected] (R.A.C.) 2 Institute of Physics, University of São Paulo, São Paulo 05508-060, SP, Brazil; [email protected] (M.C.S.); [email protected] (F.S.T.) 3 Department of Biophysics and Physiology, Federal University of Piaui, Teresina 64049-550, PI, Brazil; [email protected] 4 Ferdows School of Paramedical and Health, Birjand University of Medical Sciences, Birjand 9717853577, Iran; [email protected] 5 CICECO-Aveiro Institute of Materials & Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal; [email protected] 6 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand * Correspondence: [email protected] (P.W.); [email protected] (J.d.M.) Citation: Porto, R.; Mengarda, A.C.; Abstract: The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, Cajas, R.A.; Salvadori, M.C.; Teixeira, a disease of great global public health significance. Praziquantel is the only drug available to F.S.; Arcanjo, D.D.R.; Siyadatpanah, treat schistosomiasis and there is an urgent demand for new anthelmintic agents.