WO2015075003A1 - Réduction de la douleur chez les animaux mâles pendant la castration - Google Patents

Réduction de la douleur chez les animaux mâles pendant la castration Download PDF

Info

Publication number
WO2015075003A1
WO2015075003A1 PCT/EP2014/074800 EP2014074800W WO2015075003A1 WO 2015075003 A1 WO2015075003 A1 WO 2015075003A1 EP 2014074800 W EP2014074800 W EP 2014074800W WO 2015075003 A1 WO2015075003 A1 WO 2015075003A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
butorphanol
castration
meloxicam
pharmaceutically acceptable
Prior art date
Application number
PCT/EP2014/074800
Other languages
English (en)
Inventor
Ingo Lang
Original Assignee
Boehringer Ingelheim Vetmedica Gmbh
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 Boehringer Ingelheim Vetmedica Gmbh filed Critical Boehringer Ingelheim Vetmedica Gmbh
Publication of WO2015075003A1 publication Critical patent/WO2015075003A1/fr

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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the invention relates to the field of medicine, in particular to the field of veterinary medicine.
  • the invention relates to a preparation for the reduction of both intra-operative and post-operative pain caused by castration of male piglets.
  • male piglets are routinely surgically castrated when they are up to 7 days old.
  • the aim is to avoid the characteristic boar taint, which reduces the value of pore as it is unpleasant to humans.
  • the taint is caused by compounds that accumulate in the fat of sexually mature male pigs.
  • Castration causes pain in the concerned piglets. As of 2019, piglet castration will only be allowed under German animal welfare legislation if both intra-operative as well as postoperative pain is treated.
  • Metacam is licensed in the EU (Ref. 1). However, Metacam is not approved to treat pain during the intervention (intra-operative pain). To date, no method to alleviate surgical pain during castration is established in routine farming practice. To achieve complete surgical tolerance, basically two methods are established in medicine in general: local anaesthesia and general anaesthesia. However, neither of these two methods is suitable for piglet castration under farming conditions. Local anaesthesia was tested in controlled studies but showed not to be of advantage to the piglets. General anaesthesia can legally only be used by veterinary surgeons, but not by the farmers and therefore, there is an unmet need for a treatment and/or a preparation to alleviate surgical pain in male animals during castration without the use of general (or local) anaesthesia.
  • the problem underlying the present invention is to provide a medication to alleviate surgical pain during (and after) castration.
  • the solution to this problem is a treatment and /or medication combining meloxicam (e.g. as approved in the EU) and butorphanol.
  • Meloxicam will reduce postoperative pain, whereas butorphanol will reduce pain during the surgical intervention.
  • Butorphanol is currently not approved in pigs. The registered species are cats, dogs and horses (Ref. 3). In none of these species, butorphanol is approved to alleviate pain during soft tissue surgery or castration specifically. Butorphanol is a prescription only medicine, but it is not a scheduled drug.
  • An acceptable daily intake (ADI) and a withdrawal period for edible tissues from horses is established in the EU (Ref. 4).
  • the advantage of this solution compared to the use of meloxicam alone is that intraoperative pain is controlled better according to some parameters indicative for pain.
  • the advantage of the combined use of butorphanol and meloxicam in comparison to an opioid alone is that also post-operative pain, which is mainly inflammatory pain, is treated, as meloxicam has anti-inflammatory action.
  • Butorphanol has the advantage over most other opioids that in many countries, it is not a scheduled drug, making prescription, storage and documentation much easier.
  • oral bioavailability in humans is low, which is relevant for the evaluation of potential residues in edible tissues. In contrast to general anaesthesia, piglets will remain conscious and will not have a recovery time. Therefore, the male piglets will not be disadvantaged to the non-castrated female piglets for example in the competition for access to milk, social ranking etc..
  • Meloxicam (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H- 1 ,2-benzothiazine-3- carboxamide- 1,1 -dioxide) is a non-steroidal-antiinflammatoriy drug NSAID of the oxicam family. These types of drugs inhibit the enzyme prostaglandine H2 synthase, also called cyclooxygenase or COX. Meloxicam has antiinflammatoric, antipyretic and analgetic properties.
  • Meloxicam and its sodium and meglumine salts are described in EP0002482.
  • the active ingredient alone has a low water solubility as shown in EP0945134 that also discloses the pH dependent solubility of meloxicam and its salts.
  • There are many different application forms of meloxicam including a solution (EP 1299107), a suspension (EP 1066029), water- soluble granules (EP1558262), tablets made of either granules containing meloxicam (EP1942902) or of directly compressed powder mixtures (EP1385483 and GB2455875).
  • butorphanol (17-cyclobutylmethyl-morphinan-3,14-diol ) is well known in the art and means a mor hinan-type synthetic opioid analgesic.
  • Butorphanol exhibits partial agonist and antagonist activity at the ⁇ opioid receptor, as well as competitive antagonist activity and partial agonist activity at the ⁇ opioid receptor. Stimulation of these receptors on central nervous system neurons causes an intracellular inhibition of adenylate cyclase, closing of influx membrane calcium channels, and opening of membrane potassium channels. This leads to hyperpolarization of the cell membrane potential and suppression of action potential transmission of ascending pain pathways.
  • the advantage of butorphanol being merely a partial agonist and antagonist is that it has less abuse potential than many other opioids and is therefore not a scheduled drug. In consequence, it is a prescription only medicine (POM).
  • POM prescription only medicine
  • butorphanol is used in the form of butorphanol tartrate, preferably in a dose range between 0.05 to 0.6 mg/kg, preferably 0.2 mg/kg or less, more preferably 0.2 mg/kg.
  • pharmaceutically acceptable excipient for use with the pharmaceutical composition(s) according to the present invention include, for example, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, buffer substances, water, salts or electrolytes and cellulose-based substances. This is not a complete list possible pharmaceutically acceptable carriers, excipients and/or adjuvants, and one of ordinary skilled in the art would know other possibilities, which are replete in the art.
  • patient or “subject” means animals and embraces mammals such as primates including humans.
  • patient or “subject” as used herein relates specifically to Suidae, especially to male pigs or male piglets, more specifically to male pigs or piglets, which are routinely castrated / subject to castration.
  • slaughter in male animals, such as mammals, preferably pigs or piglets means the following: Surgical removal of the testicles.
  • the term "pain” can be measured by behavioural or biochemical variables. In piglets these are for example defense movements during castration, quality of vocalisation, time spent at the mammary gland of the sow, activity , plasma Cortisol, catecholamine or ACTH levels.
  • intra-operative pain means the following: Pain felt during the actual incision through the tissues at castration.
  • post-operative pain means the following: Pain arising after the end of the surgical intervention, which consists of inflammatory pain.
  • the behavioural or biochemical variables may vary between "intra-operative pain” and "post-operative pain”.
  • the plasma Cortisol or ACTH levels are indicative for "postoperative pain”. Reduction of pain reduces the plasma Cortisol or ACTH levels.
  • the quality of vocalization differs between presence and absence of "intra-operative pain” also referred to herein as "pain during castration".
  • an effective amount means an amount sufficient to achieve a reduction of pain in piglets during castration.
  • the progress of the therapy can be monitored by diagnosis, for example, by clinical examination, analysis of behaviour and biochemical variables. These are for example: quality of vocalisation, time spent at the mammary gland of the sow, activity, plasma Cortisol or ACTH levels.
  • catecholamine levels are indicative for stress and pain.
  • pharmaceutically acceptable derivative thereof means but is not limited to pharmaceutically acceptable salts, derivatives, metabolites or pro-drugs of a drug.
  • Derivatives as used herein include but are not limited to, any hydrate forms, solvates, isomers, enantiomers, racemates, racemic conglomerate and the like of the compound of choice.
  • Suitable pharmaceutically acceptable salts are well known in the art and may be formed with an inorganic or organic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, glycolic acid, lactic acid, pyruvic acid, malo- nic acid, succinic acid, glutaric acid, fumaric acid, malic acid, mandelic acid, tartaric acid, citric acid, ascorbic acid, palmitic acid, maleic acid, hydroxymaleic acid, benzoic acid, hy- droxybenzoic acid, phenylacetic acid, cinnamic acid, salicylic acid, methanesulfonic acid, benzenesulfonic acid and toluenesulfonic acid.
  • an inorganic or organic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, glycolic acid, lactic acid, pyru
  • a pharmaceutical composition/ preparation / medicament according to the invention may contain, as the meloxicam salt, the meglumine, sodium, potassium or ammonium salt.
  • the solubilisers used may be, for example poly ethylenegly cols (e.g. Macrogol 300), poly- oxyethylene-polyoxypropylene copolymers (e.g.poloxamer 188), glycofurol, arginine, lysine, castor oil, propyleneglycol, solketal, polysorbate, glycerol, sorbitol, mannitol, xylitol, polyvinylpyrrolidone, lecithin, cholesterol, 12-hydroxystearic acid-PEG660-ester, propyleneglycol monostearate, polyoxy-40-hydrogenated castor oil, polyoxyl-10-oleyl-ether, polyoxyl-20-cetostearylether and polyoxyl-40-stearate or a mixture of sorbitol, manni
  • the preservatives used may be, for example, ethanol, benzoic acid and the sodium or potassium salts thereof, sorbic acid and the sodium or potassium salts thereof, chlorobutanol, benzyl alcohol, phenylethanol, methyl, ethyl, propyl or butyl-p-hydroxybenzoates, phenol, m-kresol, p-chloro-m-kresol or benzalkonium chloride.
  • the buffer system may be, for example, glycine, a mixture of glycine and HC1, a mixture of glycine and sodium hydroxide solution, and the sodium and potassium salts thereof, a mixture of potassium hydrogen phthalate and hydrochloric acid, a mixture of potassium hydrogen phthalate and sodium hydroxide solution or a mixture of glutamic acid and glu- tamate.
  • excipients are citric acid, lecithin, gluconic acid, tartaric acid, phosphoric acid and EDTA or the alkali metal salts thereof, preferably tartaric acid and EDTA or the alkali metal salts thereof, particularly disodium EDTA.
  • the concentration of the solubilisers may be in the range from 20-200 mg/ml, preferably 30-150 mg/ml, preferably 40-130 mg/ml, more preferably 50-120 mg/ml, especially 70- 100 mg/ml.
  • the concentration of the preservative ethanol may be in the range from 100-200 mg/ml, preferably 120-180 mg/ml, more preferably about 150 mg/ml.
  • the concentration of the preservatives benzoic acid and the sodium or potassium salts thereof, sorbic acid and the sodium or potassium salts thereof, chlorobutanol, benzyl alcohol, phenylethanol, phenol, m-kresol and p-chloro-m-kresol may be in the range from 0.5- 50 mg/ml, preferably 1-10 mg/ml, more preferably 3-5 mg/ml.
  • the concentration of the preservatives benzalkonium chloride, phenylmercurynitrate and methyl-, ethyl-, propyl- or butyl-p-hydroxybenozates may be in the range from 0.01-4 mg/ml, preferably 0.02-3 mg/ml, more preferably 0.1-0.5 mg/ml.
  • the concentration of the buffer substances may be between 4 and 50 mg/ml, preferably between 5 and 20 mg/ml, more preferably between 8 and 10 mg/ml.
  • the concentration of the other excipients mentioned above, i.e. EDTA, citric acid, lecithin, gluconic acid, tartaric acid and phosphoric acid or the salts thereof may be in the range from 0.2-3 mg/ml, preferably 0.3-2.5 mg/ml, preferably 0.5-2 mg/ml, most preferably 0.6- 1.5 mg/ml, and in particular 0.7-1.0 mg/ml.
  • a suitable form of "administration” is for example parenteral administration, e.g. subcutaneous, intravenious or intramuscular injection (i.m.), preferably i.m..
  • parenteral administration e.g. subcutaneous, intravenious or intramuscular injection (i.m.), preferably i.m..
  • i.m. subcutaneous, intravenious or intramuscular injection
  • a preparation containing butorphanol and meloxicam is preferably used as solution for injection, preferably i.m..
  • Preferred concentration ranges of meloxicam are 1-100 mg/ml or more preferred 1-30 mg/ml, especially 5 mg/ml.
  • a preferred concentration range of butorphanol is 1-30 mg/ml, especially 5 mg/ml.
  • a suitable dosage of the pharmaceutical composition according to the present invention is in the range of:
  • meloxicam 0.1 to 1 mg/kg, especially 0.4 mg/kg once or twice at 24 h interval, preferably once.
  • butorphanol 0.05 to 0.6 mg/kg, especially 0.2 mg/kg or 0.4 mg/kg, preferably 0.2 mg/kg, once or twice after castration, preferably once.
  • the present invention concerns a pharmaceutical composition / preparation / medicament comprising (both) meloxicam or pharmaceutically acceptable salts thereof and butorphanol or pharmaceutically acceptable salts thereof (as the main and/or the sole active ingredients) and optionally a pharmaceutically acceptable excipient (or carrier), whereby said composition is preferably a liquid formulation, most preferably a solution for injection.
  • the concentration of meloxicam ranges between 1-30 mg/ml, preferably 1-5 mg/ml, most preferred the concentration of meloxicam is 5 mg/ml.
  • the concentration of butorphanol ranges between 1-30 mg/ml, preferably 1-5 mg/ml, most preferred the concentration of butorphanol is 5 mg/ml.
  • the present invention further concerns a pharmaceutical composition / preparation / medicament according to the present invention for use as a medicament in an animal, preferably in a mammal, most preferably in a Suidae such as a pig or piglet.
  • a pharmaceutical composition / preparation / medicament according to the present invention for use as a medicament in an animal, preferably in a mammal, most preferably in a Suidae such as a pig or piglet.
  • the animal is a male animal.
  • the present invention furthermore concerns a pharmaceutical composition / preparation / medicament comprising meloxicam or a pharmaceutically acceptable salt thereof in combination with butorphanol (or a pharmaceutical composition / preparation / medicament comprising butorphanol or a pharmaceutically acceptable salt thereof) for use as a medicament in an animal, preferably in a mammal, most preferably in a Suidae such as a pig or piglet.
  • the animal is a male animal.
  • the present invention further concerns a pharmaceutical composition / preparation / medicament according to the present invention for use in a method of treating pain in a male animal during and preferably also after castration, preferably said animal is a mammal, most preferably a Suidae such as a pig or piglet.
  • the present invention further concerns a pharmaceutical composition / preparation / medicament comprising meloxicam or a pharmaceutically acceptable salt thereof in combination with butorphanol (or a pharmaceutical composition / preparation / medicament comprising butorphanol or a pharmaceutically acceptable salt thereof) for use in a method of treating pain in a male animal during and preferably also after castration, preferably said animal is a mammal, most preferably a Suidae such as a pig/ piglet, whereby said compositions are preferably liquid formulations, most preferably solutions for injection.
  • the male animal is treated at least once prior to castration, preferably 10 to 60 minutes before castration, more preferably 15 to 30 minutes before castration, most preferably 20 minutes before castration.
  • castration is performed without the use of general (or local) anaesthesia.
  • the male animal is treated to reduce the pain during and after (surgical) castration.
  • no general (or local) anaesthesia is used.
  • the dose for meloxicam ranges between 0.1 to 1 mg/kg, preferably 0.4 mg/kg, and preferably the dose for butorphanol ranges between 0.05 to 0.6 mg/kg, preferably 0.2 mg/kg or 0.4 mg/kg, more preferably 0.2 mg/kg.
  • the dose for meloxicam ranges between 0.1 to 1 mg/kg, preferably 0.4 mg/kg, and preferably the dose for butorphanol ranges between 0.05 to 0.6 mg/kg, preferably 0.2 mg/kg or less, preferably 0.2 mg/kg.
  • composition(s) / preparation(s) / medicament(s) is (are) administered once or twice, preferably once.
  • the second administration occurs after a 24 h interval.
  • butorphanol is additionally administered (alone) once or twice after castration, preferably once, preferably at a dose of 0.05 to 0.6 mg/kg, most preferably at a dose of 0.2 mg/kg or 0.4 mg/kg, more preferably 0.2 mg/kg.
  • butorphanol is additionally administered (alone) once or twice after castration, preferably once, preferably at a dose of 0.05 to 0.6 mg/kg, most preferably at a dose of 0.2 mg/kg or less, preferably 0.2 mg/kg.
  • the present invention further concerns a method of treating pain in a male animal during and preferably also after castration comprising (a) administrating a therapeutically effective amount of the pharmaceutical composition / preparation / medicament (fixed dose combination) according to the present invention or (b) administrating a pharmaceutical composition / preparation / medicament comprising meloxicam or a pharmaceutically acceptable salt thereof in combination with butorphanol (a pharmaceutical composition / preparation / medicament comprising butorphanol) to a patient in need thereof, whereby said animal is preferably a mammal, most preferably a Suidae such as a pig or piglet, whereby said animal is preferably male, whereby preferably no general (or local) anaesthesia is used, whereby meloxicam and butorphanol are preferably administered 10 to 60 minutes before castration, more preferably 15 to 30 minutes before castration, most preferably 20 minutes before castration.
  • the dose for meloxicam ranges between 0.1 to 1 mg/kg, preferably 0.4 mg/kg, and preferably the dose for butorphanol ranges between 0.05 to 0.6 mg/kg, preferably 0.2 mg/kg or less, preferably 0.2 mg/kg.
  • the present invention further concerns a kit consisting of a pharmaceutical composition / preparation / medicament according to the present invention (fixed dose combination and/ or one or both active ingredients meloxicam and butorphanol separately / in separate vials), an injection device (preferably designed to inject Suidae such as a pig or piglet) suitable for parenteral administration (subcutaneously, intraveniously or intramuscular), and optionally an instruction leaflet or information and/or direction for use.
  • Suidae such as a pig or piglet
  • the present invention further concerns a kit consisting of
  • composition comprising butorphanol or a pharmaceutically acceptable salt thereof
  • an injection device suitable for parenteral administration preferably designed to inject Suidae such as pigs or piglets, and
  • a preparation containing butorphanol and meloxicam is used as solution for injection. Such preparation is injected intramuscularly to male piglets which are up to 7 days old before castration. Both butorphanol and meloxicam are used at a dosage of 0.4 mg/kg.
  • the solution for injection contains butorphanol and meloxicam at equal concentration of 5 mg/ml. Therefore, 0.08 ml are administered per kg bodyweight of the piglet. After treatment, piglets are surgically castrated.
  • Treated piglets show less pain reactions such as vocalization during castration or defense movements during castration than untreated castrated piglets and lower levels of certain stress indicators such as plasma Cortisol and catecholamines (especially adrenalin and noradrenalin) than untreated castrated piglets.
  • a preparation containing meloxicam is administered in a dose of 0.4 mg/kg i.m. into the left neck to male piglets which are up to 7 days old.
  • a preparation containing butorphanol tartrate is administered in a dose of 0.2 mg/kg i.m. into the right neck to male piglets which are up to 7 days old.
  • Surgical castration is performed 20 minutes after drug administration.
  • Treated piglets show less pain reactions such as vocalization during castration or defense movements during castration than untreated castrated piglets and lower levels of certain stress indicators such as plasma Cortisol and catecholamines (especially adrenalin and nor- adrenalin) than untreated castrated piglets.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pain & Pain Management (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte au domaine de la médecine, et plus particulièrement au domaine de la médecine vétérinaire. L'invention concerne une préparation pour réduire à la fois la douleur intra-opératoire et la douleur post-opératoire causées par la castration de porcelets mâles.
PCT/EP2014/074800 2013-11-20 2014-11-17 Réduction de la douleur chez les animaux mâles pendant la castration WO2015075003A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP13193722 2013-11-20
EP13193722.9 2013-11-20

Publications (1)

Publication Number Publication Date
WO2015075003A1 true WO2015075003A1 (fr) 2015-05-28

Family

ID=49622705

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2014/074800 WO2015075003A1 (fr) 2013-11-20 2014-11-17 Réduction de la douleur chez les animaux mâles pendant la castration

Country Status (1)

Country Link
WO (1) WO2015075003A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3458068A4 (fr) * 2016-05-17 2020-01-22 Alberta Veterinary Laboratories Ltd Composition topique pour lutter contre la douleur chez les animaux

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BUDSBERG STEVEN C ET AL: "Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs.", AMERICAN JOURNAL OF VETERINARY RESEARCH NOV 2002, vol. 63, no. 11, November 2002 (2002-11-01), pages 1557 - 1563, XP008167878, ISSN: 0002-9645 *
G F STEGMANN: "Midazolam/ketamine induction and isoflurane maintenance of anaesthesia in a 2-month-old, hand-raised African buffalo (Syncerus caffer)", JOURNAL OF THE SOUTH AFRICAN VETERINARY MEDICAL ASSOCIATION., vol. 75, no. 1, 1 March 2004 (2004-03-01), SA, pages 43 - 44, XP055105650, ISSN: 0038-2809, DOI: 10.4102/jsava.v75i1.448 *
KAZUTO YAMASHITA ET AL: "Effects of Carprofen and Meloxicam with or without Butorphanol on the Minimum Alveolar Concentration of Sevoflurane in Dogs", J. VET. MED. SCI, 1 January 2008 (2008-01-01), pages 29 - 35, XP055105520, Retrieved from the Internet <URL:https://www.jstage.jst.go.jp/article/jvms/70/1/70_1_29/_pdf> [retrieved on 20140305] *
KO JEFF C ET AL: "Evaluation of dexmedetomidine and ketamine in combination with various opioids as injectable anesthetic combinations for castration in cats.", 1 December 2011, JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION 1 DEC 2011, VOL. 239, NR. 11, PAGE(S) 1453 - 1462, ISSN: 1943-569X, XP008167864 *
MONICA HANSSON ET AL: "Effect of local anaesthesia and/or analgesia on pain responses induced by piglet castration", ACTA VETERINARIA SCANDINAVICA, BIOMED CENTRAL LTD, LO, vol. 53, no. 1, 31 May 2011 (2011-05-31), pages 34, XP021101441, ISSN: 1751-0147, DOI: 10.1186/1751-0147-53-34 *
NUSSBAUMER I ET AL: "Ferkelkastration mittels Injektionsnarkose: Erfahrungen mit der Kombination Azaperon, Butorphanol und Ketamin [Piglet castration using injection anesthesia: experiences with a combination of azaperone, butorphanol and ketamine]", SCHWEIZER ARCHIV FUER TIERHEILKUNDE, VERLAG HANS HUBER, BERN, CH, vol. 153, no. 1, 1 January 2011 (2011-01-01), pages 33 - 35, XP008167911, ISSN: 0036-7281, [retrieved on 20130314], DOI: 10.1024/0036-7281/A000140 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3458068A4 (fr) * 2016-05-17 2020-01-22 Alberta Veterinary Laboratories Ltd Composition topique pour lutter contre la douleur chez les animaux

Similar Documents

Publication Publication Date Title
Rankin Sedatives and tranquilizers
KuKanich et al. Opioids
KR20070036146A (ko) 염증성 통증 질환 치료용 수의 약제에서의 멜록시캄의 용도
JP6336592B2 (ja) ヒスタミンｈ４受容体を介してもたらされた掻痒状態を治療するための医薬組成物
US20220354834A1 (en) Methods and materials for treating neurotoxicity
US20020068692A1 (en) Method for the treatment of neurological or neuropsychiatric disorders
Ramsey et al. Cerenia Prevents Perioperative Nausea and Vomiting and Improves Recovery in Dogs Undergoing Routine Surgery.
Lin Pain management for farm animals
Guzman Advances in avian clinical therapeutics
AU2024203213A1 (en) Therapeutic formulations and uses thereof
KR20110110091A (ko) 반추 동물용 항프롤락틴성 수의학적 조성물
US11571410B2 (en) Use of carbamate compounds for prevention, alleviation or treatment of bipolar disorder
WO2015075003A1 (fr) Réduction de la douleur chez les animaux mâles pendant la castration
CA2428511C (fr) Utilisations nouvelles d&#39;agonistes 5-ht1a et d&#39;inhibiteurs de recaptage de serotinine combines
CA2808237C (fr) Compositions de buprenorphine a dose elevee et utilisation en tant qu&#39;analgesique
AU2002215027A1 (en) Novel uses of combined 5-HT1A agonists and serotonin reuptake inhibitors
US8575211B2 (en) Synergistic combination of analgesic compounds
Azari et al. Caudal epidural analgesia using lidocaine alone and in combination with tramadol in dromedary camels
EP4233854A2 (fr) Formulations thérapeutiques et leurs utilisations
ES2703693T3 (es) Métodos de tratamiento del prurito no histamínico en mamíferos
WO2009109001A1 (fr) Procédé de prévention et/ou de traitement d’une maladie, d’une condition ou d’un état associés à une fonction réduite des neurones dopaminergiques
RU2774970C2 (ru) Применение карбаматных соединений для профилактики, облегчения или лечения биполярного расстройства
RU2283648C2 (ru) Новое применение комбинированных селективных антагонистов допаминового рецептора d2 и агонистов рецептора 5-нт 1a
WO2024102458A1 (fr) Méthodes d&#39;utilisation de trazodone pour inverser les effets d&#39;agonistes du récepteur 5-ht2a
Greenacre Treatment of Pain in Small Exotic Mammals

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14802845

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14802845

Country of ref document: EP

Kind code of ref document: A1