JP5955561B2 - 反芻動物のための獣医用抗プロラクチン組成物 - Google Patents
反芻動物のための獣医用抗プロラクチン組成物 Download PDFInfo
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- JP5955561B2 JP5955561B2 JP2011530475A JP2011530475A JP5955561B2 JP 5955561 B2 JP5955561 B2 JP 5955561B2 JP 2011530475 A JP2011530475 A JP 2011530475A JP 2011530475 A JP2011530475 A JP 2011530475A JP 5955561 B2 JP5955561 B2 JP 5955561B2
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Description
本発明は、反芻動物に投与される、ドーパミン受容体の少なくとも1つの抗プロラクチン化合物アゴニストを含む獣医用組成物に関する。本発明の獣医用組成物の抗プロラクチン化合物は、エルゴリン由来のドーパミン受容体アゴニストまたは非エルゴリン由来のドーパミン受容体アゴニストから選ばれる。
本発明は、最初の搾乳および次の搾乳の時点で、治療される動物において泌乳減少を誘発するために、単回投与される、ドーパミン受容体の少なくとも1つの抗プロラクチン化合物アゴニストを含む獣医用組成物に関する。本発明は、泌乳の実質的減少を誘発するために、単回投与において、十分な治療量で投与される獣医用組成物の使用に関する。
その化学構造は、次の通りである:
これらの一連の化合物は、以前から、妊娠していない対象に投与されている。
単回注射用用量で、獣医用組成物を投与するのが有利である。
500 μg/mlのカベルゴリンを含有する注射剤9リットルの製造
処方:
有効成分:カベルゴリン 4.53 g(滴定 100 %)
賦形剤:中鎖トリグリセリド 適量 9 L.
適切な容量の容器に4.53 gのカベルゴリンおよび1.5 kgの中鎖トリグリセリドを計り入れた、次いで、完全に溶解させるために、少なくとも60分間、磁気振とう機(500回転/分)で混合物を振とうした。
乾燥した容器に5 kgの中鎖トリグリセリドを計り入れた。窒素流および混合機を設定し、次いで、ステップ1で得られた濃溶液のカベルゴリンを容器に加えた。30分間振とうを継続し、次いで、中鎖トリグリセリドを加えることによって体積を最終体積である9リットルにした。さらに30分間振とうを継続し、次いで、0.45ミクロンの調整カートリッジを通して加圧窒素下で溶液を濾過した。蒸気によって予め殺菌した適当なフラスコに濾液を集め、窒素流で乾燥した。得られた溶液を121℃にて15分間滅菌し、次いで、滅菌、無発熱物質のフラスコに入れ、ゴム栓およびアルミニウムカプセルで閉め、洗浄し、オートクレーブを通した。
この試験は、6ヶ月間の泌乳における、プリムホルスタイン種の2回以上経産した8頭の乳牛の乳汁産生の減少を評価することを目的とした。これらの乳牛の年齢は、3〜9歳であり、試験開始時における乳汁の産生レベルは、20〜31kg/日である。試験は、クロスオーバーデザイン(2処置×2期間)にしたがって準備した。
製剤は、実施例1に記載したものであり、本試験に用いる注射剤に500 μg/mlのカベルゴリンを含有する。
カベルゴリン500 μg/mlの注射剤;体重100 kg当たり1 mlに相当する、5 μg/kgの用量の筋肉内注射1回。
注射剤の製造用水、体重100 kg当たり約1 mlの処置試験における用量と同じ量を筋肉内1回注射。
処置試験薬の注射後の最初の搾乳(12時間後)から、乳汁産生の減少は、約27%であり、個体によっては42%を達成することができた。
処置試験後の7日間の観察期間中、乳汁産生の総減少は、約15 %であり、個体によっては27%を達成することができた。
この試験は、本発明で処方される投薬計画によってカベルゴリンを主成分とする獣医用組成物を過剰投与した場合でさえも、妊娠している反芻動物におけるカベルゴリンの使用中に、流産および胎児毒性などのリスクがないことを示すことを目的とした。異なる妊娠段階にある乳牛のグループに異なる用量で処置薬を与える。
妊娠7〜8ヶ月(5頭):15 μg/kgの用量、48時間間隔で2回注射;
妊娠6.5〜7.5ヶ月(11頭):25 μg/kgの用量、48時間間隔で2回注射。
製剤は、実施例1に記載したものであり、本試験に用いる注射剤に500 μg/mlのカベルゴリンを含有する。
毎日の全般検査および流産;
苦痛および胎児生存能力を評価するための経直腸触診および超音波などの生殖管の臨床検査。
さらに、動物は一般に、この処置によく耐えた。結論として、25 μg/kgまでの用量にて48時間間隔でカベルゴリンを1回または2回投与することは、妊娠している乳牛にとって少なくとも危険ではない。
乳汁産生レベルが約18 kgの約7ヶ月間妊娠しているプリムホルスタイン種の2回以上経産した9頭の乳牛(約600 kg)を本試験に用いる。試験は、クロスオーバー(2処置×2期間)、休薬3週間として行う。
動物は、筋肉内注射製剤により、処置試験を受ける。
キナゴリド0.5 mg/mlの注射剤;体重100 kg当たり1 mlに相当する、1〜3 mg/乳牛の用量の筋肉内注射1回。
処置コントロール(プラセボ):
注射剤の製造用水、体重100 kg当たり約1 mlの処置試験における用量と同じ量を筋肉内1回注射。
処置日の前後の7日間、各期間に対して、乳汁産生の追跡を行い、全試験期間を通して、実施例3と同様の流産の調査を行う。
乳汁産生レベルが約18 kgの約7ヶ月間妊娠しているプリムホルスタイン種の2回以上経産した9頭の乳牛(約600 kg)を本試験に用いる。試験は、クロスオーバー(2処置×2期間)、休薬3週間として行う。
動物は、筋肉内注射製剤により、処置試験を受ける。
ブロモクリプチン10 mg/mlの注射剤;体重100〜50 kg当たり1 mlに相当する、100〜200 μg/kgの用量の筋肉内注射1回。
処置コントロール(プラセボ):
注射剤の製造用水、体重100 kg当たり約1 mlの処置試験における用量と同じ量を筋肉内1回注射。
処置日の前後の7日間、各期間に対して、乳汁産生の追跡を行い、全試験期間を通して、実施例3と同様の流産の調査を行う。
Claims (10)
- 妊娠している雌ウシにおいて、有害または流産を起こしうる作用を引き起こすことなく治療有効量で投与される、妊娠している雌ウシの泌乳を減少させるための獣医用組成物の製造のための、カベルゴリンの使用。
- 組成物が、5〜60%、20〜50%または25〜35%の泌乳減少を誘発するための治療有効量で投与される、請求項1に記載の使用。
- 泌乳減少が、組成物の処置後7日間まで得られる、請求項1または2に記載の使用。
- 泌乳減少が、処置後の最初の搾乳および次の搾乳中に起こる、請求項1〜3のいずれか1つに記載の使用。
- 獣医用組成物が、非経口、皮膚または経口経路により投与される、請求項1〜4のいずれか1つに記載の使用。
- 獣医用組成物が、注射により投与される、請求項1〜5のいずれか1つに記載の使用。
- 組成物が、筋肉内注射または皮膚注射による単回投与として投与される、請求項6に記載の使用。
- 獣医用組成物が、雌ウシ当たり、および処置当たりの単回治療有効量で投与される、請求項1〜7のいずれか1つに記載の使用。
- 妊娠している雌ウシの泌乳を減少させるための治療有効量の請求項1〜8のいずれか1つに記載の獣医用組成物を含む獣医用キット。
- 獣医用組成物の運用方法および投与方法に関する指示書をさらに含む請求項9に記載のキット。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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FR0805544A FR2936710B1 (fr) | 2008-10-07 | 2008-10-07 | Composition veterinaire antiprolactinique destinee aux ruminants |
FR0805544 | 2008-10-07 | ||
PCT/EP2009/063004 WO2010040765A1 (fr) | 2008-10-07 | 2009-10-07 | Composition veterinaire antiprolactinique destinee aux ruminants |
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JP2012505178A JP2012505178A (ja) | 2012-03-01 |
JP2012505178A5 JP2012505178A5 (ja) | 2012-06-07 |
JP5955561B2 true JP5955561B2 (ja) | 2016-07-20 |
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EP (1) | EP2349272B1 (ja) |
JP (1) | JP5955561B2 (ja) |
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CN (1) | CN102215843B (ja) |
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CA (1) | CA2738875C (ja) |
DK (1) | DK2349272T3 (ja) |
ES (1) | ES2719844T3 (ja) |
FR (1) | FR2936710B1 (ja) |
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HU (2) | HUE043239T2 (ja) |
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RU (1) | RU2528892C2 (ja) |
SI (1) | SI2349272T1 (ja) |
UA (1) | UA103779C2 (ja) |
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FR2971423B1 (fr) * | 2011-02-15 | 2014-01-10 | Ceva Sante Animale | Composition veterinaire antiprolactinique destinee aux ruminants |
EP2995297A1 (fr) * | 2014-09-09 | 2016-03-16 | Ceva Sante Animale | Compositions parentérales et leurs utilisations |
GB2571696B (en) | 2017-10-09 | 2020-05-27 | Compass Pathways Ltd | Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced |
KR20220008824A (ko) | 2019-04-17 | 2022-01-21 | 컴퍼스 패쓰파인더 리미티드 | 실로시빈으로 불안 장애, 두통 장애 및 섭식 장애를 치료하는 방법 |
US11759474B2 (en) | 2019-11-28 | 2023-09-19 | Boehringer Ingelheim Vetmedica Gmbh | Use of SGLT-2 inhibitors in the drying-off of non-human mammals |
UY39022A (es) | 2020-01-27 | 2021-07-30 | Ceva Sante Animale | Composición veterinaria de anti-prolactina para rumiantes utilizada mediante administración intramamaria |
UY39019A (es) * | 2020-01-27 | 2021-07-30 | Ceva Sante Animale | Composición veterinaria para rumiantes lecheros para el tratamiento de la fiebre de la leche |
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US4839171A (en) * | 1984-11-30 | 1989-06-13 | Techmix, Inc. | Composition for treating impaired lactation |
US4939259A (en) * | 1989-07-24 | 1990-07-03 | Eli Lilly And Company | 2-oxo-pyrido[2,3-g]quinoline derivatives |
AU2635599A (en) * | 1999-03-17 | 2000-10-04 | Eugen Eigenmann | Use of prolactin inhibitors for the treatment of fertility problems in animal species |
GB0108485D0 (en) * | 2001-04-04 | 2001-05-23 | Pfizer Ltd | Combination therapy |
NZ515178A (en) * | 2001-11-23 | 2004-09-24 | Agres Ltd | Modulating prolactin receptors to affect a physiological response |
GB0313892D0 (en) * | 2003-06-16 | 2003-07-23 | Hannah Res Inst | Control of lactation |
GB0314469D0 (en) | 2003-06-20 | 2003-07-23 | Phico Therapeutics Ltd | Antimicrobial compositions and uses thereof |
CN1762495B (zh) * | 2004-09-21 | 2011-04-06 | 山东绿叶制药有限公司 | 含有多巴胺受体激动剂类药物的长效缓释制剂及其制备工艺 |
WO2006032202A1 (en) * | 2004-09-21 | 2006-03-30 | Shandong Luye Pharmaceutical Co., Ltd. | Long acting sustained-release formulation containing dopamine receptor agonist and the preparation method thereof |
EP1952813A1 (en) * | 2007-02-01 | 2008-08-06 | Ferring International Center S.A. | Medicament for the treatment of endometriosis |
ITTO20070479A1 (it) * | 2007-07-02 | 2009-01-03 | Ceva Vetem S P A | Composizione veterinaria iniettabile ad attivita' anti-prolattinica |
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