EP1381374A1 - Compositions veterinaires comprenant des derives d'oxime avermectine et du praziquantel - Google Patents

Compositions veterinaires comprenant des derives d'oxime avermectine et du praziquantel

Info

Publication number
EP1381374A1
EP1381374A1 EP02716978A EP02716978A EP1381374A1 EP 1381374 A1 EP1381374 A1 EP 1381374A1 EP 02716978 A EP02716978 A EP 02716978A EP 02716978 A EP02716978 A EP 02716978A EP 1381374 A1 EP1381374 A1 EP 1381374A1
Authority
EP
European Patent Office
Prior art keywords
praziquantel
selamectin
monosaccharide
formulation
treatment
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP02716978A
Other languages
German (de)
English (en)
Inventor
Bernard Frank Pfizer Central R & D BISHOP
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pfizer Ltd
Pfizer Inc
Original Assignee
Pfizer Ltd
Pfizer Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pfizer Ltd, Pfizer Inc filed Critical Pfizer Ltd
Publication of EP1381374A1 publication Critical patent/EP1381374A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the invention described herein relates to the provision of a combination therapy in the field of treatment (including prophylaxis) of parasitic infestations and consequences thereof, particularly in veterinary medicine.
  • the invention relates to antiparasitic therapy using a combination of avermectin- like compounds, specifically 13-monosaccharide-5-oxime compounds, and praziquantel.
  • EP 0 717 993 describes a synergistic combination of avermectins/milbemycins with praziquantel, in particular for the treatment of cestode and nematode infestations in horses.
  • Particular species mentioned therein include Anoplocephala perfiolata, Strongylidae, Gasterophilus spp., and Parascari aquorum.
  • Particular avermectins mentioned therein include ivermectin, abamectin, moxidectin and doramectin.
  • Formulations of selamectin in di(C 2 -4 glycol) mono(C ⁇ -4 alkyl) ethers including dipropylene glycol monomethyl ether (DPGMME), and alcohols such as ethanol and isopropy alcohol (IPA) are disclosed in International Patent Application, publication no. WO00/30449, herein incorporated by reference.
  • DPGMME dipropylene glycol monomethyl ether
  • IPA isopropy alcohol
  • Selamectin is the active ingredient of the product marketed under the trade names RevolutionTM, StrongholdTM, etc. by Pfizer Inc. and associated companies, particularly for the treatment (including prophylaxis) of endo- and ecto-parasite infestations in companion animals such as cats and dogs.
  • Praziquantel is 2-(cyclohexylcarbonyl)-1 ,2,3,6,7-11b-hexahydro-4H- pyrazino[2,1-a]isoquinolin-4-one, also known as an active ingredient in EMBAY 8440TM, BiltricideTM, CesolTM, and DroncitTM. It is mentioned in the Merck Index, 11th edition, para.7714, and references therein, herein incorporated by reference.
  • Desirable attributes in particular for a topical application for administration to companion animals such as cats and dogs, and especially in relation to a treatment for the control of flea, heartworm and tapeworm infestation, include: efficacy; persistence of efficacy; low volume; cosmetically acceptable; convenient; need for small number of applications for broad spectrum parasite control; compliant treatment; safe; suitable pharmacokinetic profile; suitable transdermal flux profile; rapid rate of onset; low dose of active ingredient(s); cutaneous tolerability; and stability on storage.
  • Praziquantel has a widespread use in animals orally at higher doses than those which we have tested.
  • Dr. J.A. Shmidl in Shawnee, Kansas treated two cats orally with doses of 25 and 50 mg/kg. There were no signs of clinical toxicity or evidence of gross lesions in the gastrointestinal tract.
  • Dr. S.M. Kruckenberg reports on the oral treatment of seven cats (6 females and 1 male) with a 5 mg/kg dose during all critical periods of reproduction. Two groups of seven cats (6 females and 1 male) each were also treated subcutaneously and intramuscularly with a praziquantel injectable solution with a 5 mg/kg dose during all critical periods of reproduction. Dr. Kruckenberg further evaluated the oral use of praziquantel in one male and three female cats in a controlled study. Two groups of 4 cats (1 male and 3 females) each were also treated subcutaneously and intramuscularly with the praziquantel injectable solution. All treated cats received 3X the label rate. Four females and 1 male served as untreated controls.
  • the treated males received 7 treatments at 2-week intervals throughout the breeding season. Each treated female received a treatment prior to breeding, during the embryogenic period of pregnancy, during late pregnancy and again during lactation.
  • the study confirmed the lack of effects on fertility, conception, fetal development or pregnancy when praziquantel was administered at 3X dosage levels.
  • Dr. Shmidl further treated two kittens (4 1/2 to 7 1/2 weeks old) twice at a 14- day interval.
  • the dosage rate was 5X the label dose. Slight depression was observed in one kitten. No significant clinical toxicity signs or clinical pathology and histopathology changes were attributed to this dosage rate.
  • the safety index for the use of praziquantel tablets in cats has been derived from controlled studies using the final tablet formulation (vomiting was the only effect with dual treatments of 100 mg/kg at a 14-day interval). Vomiting at high dosage rates is the typical reaction which prevents significant clinical toxicity signs from occurring.
  • the safety factor is at least 5X the label rate when the product is administered at 14 day intervals to kittens 5 1/2 weeks of age and older.
  • CUTTER Tape-Tabs (praziquantel) Tapeworm Tablets will remove the common tapeworms, Dipylidium caninum and Taenia taeniaeformis , from cats and kittens.
  • CUTTER Tape-Tabs (praziquantel) Tapeworm Tablets for Cats and Kittens are sized for easy administration to either adult cats or kittens.
  • the tablets may be given directly in the mouth or crumbled and mixed with the food.
  • praziquantel tablets were 100% effective in the treatment of tapeworm infections of dogs and cats due to Taenia pisiformis , Taenia taeniaeformis and Dipylidium caninum. Additionally praziquantel effectively (100%) eliminated experimental T. taeniaeformis infections as young as seven (7) days from cats. Summary of Preclinical Effectiveness Data for Praziquantel Tablets in Cats
  • praziquantel has a solubility above 60 mg/g (6% w/w) even in the presence of selamectin at up to 120 mg/g (12% w/w). Above 50% IPA however, this solubility may be increased to over 90 mg/g (9% w/w) in the supersaturated state.
  • a series of IPA / DPGMME mixtures were prepared in duplicate as outlined in Table 1. To these were added a fixed amount of selamectin to provide a constant concentration of 120 mg per ml i.e. the maximum selamectin concentration found in StrongholdTM.
  • Praziquantel was analysed using an gradient HPLC method modified from that developed for selamectin. This method was validated with respect to praziquantel linearity over the range 10 to 200 mg per ml of praziquantel (in the solubility test solutions) and in the presence of 120 mg per ml of selamectin. This same method was also used to check on the selamectin content in these same solutions.
  • compositions containing selamectin and praziquantel are shown below, wherein the composition within the formulation is expressed % weight by volume:
  • An aspect of the invention is the provision of a combination therapy using a formulation comprising a 13-monosaccharide 5-oxime avermectin such as selamectin at around 6-12% w/v, and praziquantel at around 3-9% w/v (preferably around 6% w/v), in a veterinarily acceptable carrier, diluent or adjuvant.
  • a formulation comprising a 13-monosaccharide 5-oxime avermectin such as selamectin at around 6-12% w/v, and praziquantel at around 3-9% w/v (preferably around 6% w/v), in a veterinarily acceptable carrier, diluent or adjuvant.
  • the (13-monosaccharide 5-oxime avermectin such as selamectin)- containing formulation comprises a di(C 2 - 4 glycol) mono(C 1 ⁇ alkyl) ether and an optional skin-acceptable solvent.
  • the (13-monosaccharide 5-oxime avermectin such as selamectin)- containing formulation is suitable for topical, preferably spot-on, application.
  • Another aspect of the invention is the provision of an antiparasitic combination therapy whereby a 13-monosaccharide 5-oxime avermectin such as selamectin is provided at around 6-12mg/kg (re. host animal) and praziquantel is provided at up to 18mg/kg (re. host animal).
  • a 13-monosaccharide 5-oxime avermectin such as selamectin is provided at around 6-12mg/kg (re. host animal) and praziquantel is provided at up to 18mg/kg (re. host animal).
  • the selamectin is present in the formulation at about 1 % to about 16% (w/v), more preferably about 4% to about 12% w/v, and most preferably about 6% to about 12% w/v.
  • Specific preferred formulations contain selamectin at about 6% w/v and about 12% w/v.
  • the praziquantel is present in the formulation at about 0.5 to about 10% w/v, more preferably about 3 to about 9% w/v , most preferably about 6% w/v.
  • the di(C 2-4 glycol) mono(C ⁇ - alkyl) ether is diethylene glycol monomethyl ether (DEGMME) or dipropylene glycol monomethyl ether (DPGMME), more preferably DPGMME.
  • DEGMME diethylene glycol monomethyl ether
  • DPGMME dipropylene glycol monomethyl ether
  • the skin-acceptable solvent is present and is ethanol or isopropanol, more preferably isopropanol.
  • the formulation containing the avermectin 13-monosaccharide oxime has a w/v to v/v ratio of avermectin 13-monosaccharide oxime to the glycol monomethyl ether is in the range (0.5 to 2) to 1 , more preferably (0.7 to 1.4) to 1 , yet more preferably (0.9 to 1.1 ) to 1 , most preferably about 1 :1.
  • a preferred formulation according to the invention also contains antioxidant, preferably selected from propylgallate, BHA (2-t-butyl-4-methoxyphenol), and BHT (2,6-di-f-butyl-4-methylphenol), more preferably BHT.
  • antioxidant preferably selected from propylgallate, BHA (2-t-butyl-4-methoxyphenol), and BHT (2,6-di-f-butyl-4-methylphenol), more preferably BHT.
  • a preferred formulation according to the invention consists of:
  • DEGMME or DPGMME at 1 to 16% w/v, and at a w/v or v/v ratio of active compound to DEGMME/DPGMME of about 1 :1 ;
  • a more preferred formulation consists of (a) selamectin at a level of 6% to 12% w/v;
  • a pharmaceutical or veterinary composition which comprises a 13- monosaccharide 5-oxime avermectin such as selamectin and praziquantel and a pharmaceutical or veterinary carrier;
  • kits useful in the treatment of a parasitic infestation of flea and/or heartworm and tapeworm in a mammal which comprises a 13- monosaccharide 5-oxime avermectin, such as selamectin, and praziquantel and a pharmaceutical or veterinary carrier, and instructions for the treatment of a parasitic infestation of flea and/or heartworm and tapeworm in a mammal.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une polythérapie antiparasitaire faisant appel à une combinaison d'un 5-oxime avermectine monosaccharide 13, tel que de la sélamectine, et du praziquantel.
EP02716978A 2001-04-04 2002-03-28 Compositions veterinaires comprenant des derives d'oxime avermectine et du praziquantel Withdrawn EP1381374A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB0108485.4A GB0108485D0 (en) 2001-04-04 2001-04-04 Combination therapy
GB0108485 2001-04-04
PCT/IB2002/001025 WO2002094288A1 (fr) 2001-04-04 2002-03-28 Compositions veterinaires comprenant des derives d'oxime avermectine et du praziquantel

Publications (1)

Publication Number Publication Date
EP1381374A1 true EP1381374A1 (fr) 2004-01-21

Family

ID=9912257

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02716978A Withdrawn EP1381374A1 (fr) 2001-04-04 2002-03-28 Compositions veterinaires comprenant des derives d'oxime avermectine et du praziquantel

Country Status (7)

Country Link
EP (1) EP1381374A1 (fr)
JP (1) JP2004526804A (fr)
BR (1) BR0208654A (fr)
CA (1) CA2443068A1 (fr)
GB (1) GB0108485D0 (fr)
MX (1) MXPA03009023A (fr)
WO (1) WO2002094288A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2528892C2 (ru) * 2008-10-07 2014-09-20 Сева Санте Анималь Са Ветеринарная антипролактиновая композиция для жвачных

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1610613T3 (en) * 2003-04-04 2017-02-27 Merial Inc TOPICAL ANTHELMINTIC VETERINARY FORMULATIONS
DE10358525A1 (de) 2003-12-13 2005-07-07 Bayer Healthcare Ag Endoparasitizide Mittel zur topischen Applikation
EP2408771B1 (fr) 2009-03-17 2016-11-16 Concert Pharmaceuticals, Inc. Composés de pyrazinoisoquinoline
GB0905365D0 (en) 2009-03-27 2009-05-13 Norbrook Lab Ltd A topical parasiticide composition
UA108641C2 (uk) 2010-04-02 2015-05-25 Паразитицидна композиція, яка містить чотири активних агенти, та спосіб її застосування
JP5723567B2 (ja) * 2010-08-06 2015-05-27 丸石製薬株式会社 含窒素複素環式化合物の定量方法
HUE041514T2 (hu) 2012-02-06 2019-05-28 Merial Inc Szisztémásan ható hatóanyagokat tartalmazó, parazitaellenes, szájon át adagolt állatgyógyászati készítmények, eljárások és alkalmazásuk
JP6088637B2 (ja) 2012-04-04 2017-03-01 インターベット インターナショナル ベー． フェー． イソオキサゾリン化合物のための固形経口医薬組成物

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9300883D0 (en) * 1993-01-18 1993-03-10 Pfizer Ltd Antiparasitic agents
BG61064B1 (bg) * 1993-08-12 1996-10-31 Илия Илиев Лекарствено средство за обезпаразитяване на животни
AUPM969994A0 (en) * 1994-11-28 1994-12-22 Virbac S.A. Equine anthelmintic formulations
WO1998006407A1 (fr) * 1996-07-30 1998-02-19 Ashmont Holdings Limited Formulations anti-helminthes
GB9825402D0 (en) * 1998-11-19 1999-01-13 Pfizer Ltd Antiparasitic formulations

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO02094288A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2528892C2 (ru) * 2008-10-07 2014-09-20 Сева Санте Анималь Са Ветеринарная антипролактиновая композиция для жвачных

Also Published As

Publication number Publication date
JP2004526804A (ja) 2004-09-02
CA2443068A1 (fr) 2002-11-28
MXPA03009023A (es) 2004-02-12
BR0208654A (pt) 2004-03-09
GB0108485D0 (en) 2001-05-23
WO2002094288A1 (fr) 2002-11-28

Similar Documents

Publication Publication Date Title
US6797701B2 (en) Antiparasitic formulations
US20070010464A1 (en) Avermectin and praziquantel combination therapy
AU695582B2 (en) Anthelmintic formulations
JPH0623100B2 (ja) 改良された抗寄生虫活性を持つ非水性イベルメクチン処方剤
EP1478372A1 (fr) Composition anti-parasitaire longue duree contenant un compose salicylanilide, une espece polymerique et au moins un autre compose anti-parasite
RU2124290C1 (ru) Препаративная форма в виде раствора для местного применения для обработки животных (варианты), способ получения и способ обработки животных (варианты)
AU2006322120B2 (en) Benzimidazole non-aqueous compositions
EP1381374A1 (fr) Compositions veterinaires comprenant des derives d'oxime avermectine et du praziquantel
US20050245468A1 (en) Anthelmintic composition
EP2895168A2 (fr) Formulations pharmaceutiques de tétrandrine et procédé associé
AU2012273538B2 (en) Anti-parasitic composition comprising a macrocyclic lactone and levamisole and method of treatment of parasitic infestation
WO2001064222A1 (fr) Compositions veterinaires destinees au traitement de maladies parasitaires
AU2001235489A1 (en) Veterinary compositions for the treatment of parasitic diseases
CN110721152A (zh) 一种治疗动物皮肤寄生虫、真菌感染的缓释组合物
WO1998018463A1 (fr) Formulation anthelmintique
Buchmann et al. Effect of ivermectin, pyrantel and morantel on the European eel and its monogenean parasites
Paul et al. Efficacy of ivermectin against Dirofilaria immitis in cats 30 and 45 days post-infection.
US20090017089A1 (en) Multiple active agents such as anthelmintics sustained release delivery device
Ekinci et al. ANTIPARASITIC DRUGS USED THE IN TREATMENT OF DEMODICOSIS IN DOGS: 2022 LITERATURE REVIEW
CN115671040A (zh) 一种控制动物寄生虫感染的外用制剂
EP1713468B9 (fr) Composition anthelminthique
NZ537760A (en) Worming formulations comprising a macrocyclic lactone and piperonyl butoxide

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20030926

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

17Q First examination report despatched

Effective date: 20050719

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20061219