[go: up one dir, main page]

WO2009003965A1 - Composition à usage vétérinaire injectable dotée d'activité anti-prolactine - Google Patents

Composition à usage vétérinaire injectable dotée d'activité anti-prolactine Download PDF

Info

Publication number
WO2009003965A1
WO2009003965A1 PCT/EP2008/058324 EP2008058324W WO2009003965A1 WO 2009003965 A1 WO2009003965 A1 WO 2009003965A1 EP 2008058324 W EP2008058324 W EP 2008058324W WO 2009003965 A1 WO2009003965 A1 WO 2009003965A1
Authority
WO
WIPO (PCT)
Prior art keywords
cabergoline
composition according
mcg
prolactin
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.)
Ceased
Application number
PCT/EP2008/058324
Other languages
English (en)
Inventor
Claudio Zanichelli
Renzo Ballabio
Andrea Fiorentini
Isidoro Schachter
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.)
Ceva Vetem SpA
Original Assignee
Ceva Vetem SpA
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 Ceva Vetem SpA filed Critical Ceva Vetem SpA
Publication of WO2009003965A1 publication Critical patent/WO2009003965A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • Cabergoline ⁇ l-[-((6-allylergoline-8 ⁇ -yl)carbonyl)]-l-[-3-(dimethyl amino)propyl] -3- ethylurea ⁇ is a drug which is known both for its strong anti-prolactin activity, and for its prolonged duration of action and low toxicity.
  • Cabergoline has a wide margin of safety: the therapeutic index (DL 50 and DE 50 ratio) thereof in the rat is 13,000.
  • a veterinary drug for oral administration is commercially available, which contains cabergoline in a concentration of 50 mcg/ml in a solvent composed of medium chain triglycerides.
  • Such medicament sold under the trade name GALASTOP®, can be either administered directly into the mouth of the animal, or mixed with food.
  • GALASTOP® finds its reason for use in those conditions governed by prolactin, such as pseudopregnancy and postpartum lactation in female dogs and cats.
  • the present invention further relates to a pharmaceutical or veterinary product comprising a container or a bottle which has been specifically designated to allow storage of the cabergoline composition under stable conditions, without any degradation or oxidation, for long periods of time, even when the containers are stored upside down.
  • a pharmaceutical or veterinary product comprising a container or a bottle which has been specifically designated to allow storage of the cabergoline composition under stable conditions, without any degradation or oxidation, for long periods of time, even when the containers are stored upside down.
  • Such containers or bottles are filled with the composition as described above and are equipped with a closure rubber stopper in nitrile or chlorobutyl rubber coated with a fluoropolymeric film.
  • rubber stopper made of in nitrile or chlorobutyl rubber coated with a fluoropolymeric film have surprisingly showed no adsorption of cabergoline, allowing to store the containers in all positions for long period of time, even in the upside down position.
  • kits intended for veterinary use and for treatment of non human animals affected by disorders associated to an increase of prolactin.
  • kits may the container and the pharmaceutical compositions of cabergoline as previously described, as well as instructions on the mode of administration of the composition to a subject.
  • Step 2 in a dry solution vessel, 30 kg medium chain triglycerides is dosed; the nitrogen flow and stirring is initiated, then the cabergoline concentrated solution which has been obtained in step 1 is poured in the solution vessel; it is kept under stirring for 30 minutes, then it is brought up to the end volume of 50 L with medium chain triglycerides; then, stirring is resumed for additional 30 minutes; it is filtered under nitrogen pressure through a 0.45 ⁇ m cartridge; filtrate is collected in an storage tank already sanitized in a flow of vapour, and dried in a nitrogen stream; the obtained solution is sterilized at 121 °C for 15 minutes; then, the solution is dosed into sterilized and depyrogenated bottles equipped with rubber stoppers and aluminium caps, also washed and autoclaved.
  • the test has been divided in three STEPS.
  • the doses used were 1.5 mcg/kg p.v. for two administrations at 0 and 48 hours, or 0 and 72 hours in the STEPS I and II, or 3.0 mcg/kg p.v. in a single administration in STEP III.
  • Results showed that the injectable formulation VEGA administered subcutaneously at a dose of 1.5 mcg/kg/day at 0 hours and after 48 or 72 hours, determines a remission of the pseudopregnancy symptoms in the female dog.
  • the test showed how the remission of symptoms is produced in a lesser period of time in the subject treated with VEGA, which in a high (70-90%) percentage were completely recovered already at the sixth day after the administration, unlike 20% subjects treated with oral preparation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une composition à usage vétérinaire destinée à une administration parentérale et dotée d'une activité anti-prolactine, ayant une concentration de cabergoline faible, comprise entre 10 et 40 mcg/ml, dans un solvant huileux. Le choix du véhicule, du conditionnement primaire, et du procédé de production garantit le respect des exigences pertinentes et l'obtention de la qualité nécessaire pour l'administration parentérale et la stabilité de la formulation tant dans son conditionnement intact qu'après le premier retrait.
PCT/EP2008/058324 2007-07-02 2008-06-27 Composition à usage vétérinaire injectable dotée d'activité anti-prolactine Ceased WO2009003965A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITTO20070479 ITTO20070479A1 (it) 2007-07-02 2007-07-02 Composizione veterinaria iniettabile ad attivita' anti-prolattinica
ITTO2007A000479 2007-07-02

Publications (1)

Publication Number Publication Date
WO2009003965A1 true WO2009003965A1 (fr) 2009-01-08

Family

ID=39768760

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/058324 Ceased WO2009003965A1 (fr) 2007-07-02 2008-06-27 Composition à usage vétérinaire injectable dotée d'activité anti-prolactine

Country Status (2)

Country Link
IT (1) ITTO20070479A1 (fr)
WO (1) WO2009003965A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110245261A1 (en) * 2008-10-07 2011-10-06 Ceva Sante Animale Sa Antiprolactinic veterinary composition for ruminants
US20200375980A1 (en) * 2018-01-30 2020-12-03 Ceva Sante Animale Veterinary antiprolactinic composition
IT201900009777A1 (it) 2019-06-21 2020-12-21 Procos Spa Processo per la sintesi di lofexidina

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006117608A1 (fr) * 2005-04-29 2006-11-09 Ferring International Center S.A. Traitement ou prevention du syndrome d'hyperstimulation ovarienne (ohss) au moyen d'un agoniste de la dopamine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006117608A1 (fr) * 2005-04-29 2006-11-09 Ferring International Center S.A. Traitement ou prevention du syndrome d'hyperstimulation ovarienne (ohss) au moyen d'un agoniste de la dopamine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ARBEITER K ET AL: "TREATMENT OF PSEUDOPREGNANCY IN THE BITCH WITH CABERGOLINE AN ERGOLINE DERIVATIVE", JOURNAL OF SMALL ANIMAL PRACTICE, vol. 29, no. 12, 1988, pages 781 - 788, XP002497977, ISSN: 0022-4510 *
ONCLIN K ET AL: "Termination of unwanted pregnancy in dogs with the dopamine agonist, cabergoline, in combination with a synthetic analog of PGF2-alpha, either cloprostenol or alphaprostol", THERIOGENOLOGY, vol. 43, no. 4, 1995, pages 813 - 822, XP002497976, ISSN: 0093-691X *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110245261A1 (en) * 2008-10-07 2011-10-06 Ceva Sante Animale Sa Antiprolactinic veterinary composition for ruminants
US9730923B2 (en) 2008-10-07 2017-08-15 Ceva Sante Animale Antiprolactinic veterinary composition for ruminants
US9744158B2 (en) 2008-10-07 2017-08-29 Ceva Sante Animale Veterinary antiprolactinic composition for ruminants
US20200375980A1 (en) * 2018-01-30 2020-12-03 Ceva Sante Animale Veterinary antiprolactinic composition
EP3746074A1 (fr) * 2018-01-30 2020-12-09 Ceva Sante Animale Composition antiprolactinique vétérinaire
IT201900009777A1 (it) 2019-06-21 2020-12-21 Procos Spa Processo per la sintesi di lofexidina
WO2020254580A1 (fr) 2019-06-21 2020-12-24 Procos S.P.A. Procédé de synthèse de lofexidine
EP4071139A1 (fr) 2019-06-21 2022-10-12 Procos S.p.A. Hydrochloride crystalline de lofexidine

Also Published As

Publication number Publication date
ITTO20070479A1 (it) 2009-01-03

Similar Documents

Publication Publication Date Title
US7834056B2 (en) Pharmaceutical composition for gout
JP3723857B2 (ja) ヒト成長ホルモン含有水性医薬組成物
CZ25793A3 (en) Pharmaceutical mixtures of phlorphenicol
HK1050317A1 (zh) 防腐的药物制剂
CN101953841B (zh) 一种抗猪附红细胞体病的复方长效土霉素注射液及其制备方法
KR20050109561A (ko) 허용가능한 혈청 테스토스테론 수준의 신뢰성 있는 달성을위한 방법 및 제약 조성물
EP2349272B1 (fr) Composition veterinaire antiprolactinique destinee aux ruminants
JP6502507B2 (ja) スルホンアミド系医薬組成物の調製方法
WO2009003965A1 (fr) Composition à usage vétérinaire injectable dotée d'activité anti-prolactine
CA2865555C (fr) Compositions a liberation controlee et leurs procedes d'utilisation
WO2011034464A1 (fr) Forme pharmaceutique injectable pour le traitement de l'ictus ischémique aigu et du traumatisme crânien, son procédé de fabrication et d'utilisation
JPH08507774A (ja) 手術後の悪心および嘔吐の治療のためのグラニセトロンの使用
CN114469971B (zh) 白头翁皂苷b5在制备治疗阳痿药物中的应用
CN108404121A (zh) 一种重组人生长激素注射液及其制备方法
CN105640956B (zh) 不含防腐剂的复方磷酸可待因组合口服液及其制备方法
RU2442573C1 (ru) Способ лечения дизентерии свиней
WO2011095801A2 (fr) Composition pharmaceutique
CN102258507A (zh) 含有布洛芬的药物组合物及其制备方法和应用
RU2074727C1 (ru) Способ лечения и профилактики желудочно-кишечных заболеваний телят и поросят
CN105935443A (zh) 一种治疗糖尿病性白内障的药物组合物
CN109364067B (zh) 一种化合物在制备提高血脑屏障通透性药物中的用途
CN112076310A (zh) 一种治疗多发性硬化的药物组合物及其制备
RU2813546C1 (ru) Средство для лечения и профилактики послеродовых заболеваний у коров
RU2238086C2 (ru) Новая лекарственная форма n-(4-нитро-2-феноксифенил) метансульфонамида, способ ее получения и применения
CN103285013B (zh) 一种防治牛猪肺炎疾病的药物组合物及其制备方法

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: 08774483

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: 08774483

Country of ref document: EP

Kind code of ref document: A1