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CN1921865B - 美洛昔康用于治疗猪呼吸系统疾病的用途 - Google Patents

美洛昔康用于治疗猪呼吸系统疾病的用途 Download PDF

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CN1921865B
CN1921865B CN2005800054227A CN200580005422A CN1921865B CN 1921865 B CN1921865 B CN 1921865B CN 2005800054227 A CN2005800054227 A CN 2005800054227A CN 200580005422 A CN200580005422 A CN 200580005422A CN 1921865 B CN1921865 B CN 1921865B
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英戈·U·兰
约安尼斯·帕佩特萨斯
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Abstract

本发明是关于美洛昔康或其可药用盐在制备用于治疗或预防猪呼吸系统疾病的药物组合物中的用途。

Description

美洛昔康用于治疗猪呼吸系统疾病的用途
发明背景
技术领域
本发明是关于美洛昔康或其可药用的盐在制备用于治疗或预防猪呼吸系统疾病的药物组合物中的用途。
背景技术
在猪养殖中，猪呼吸系统疾病属于最重要的健康问题。猪呼吸系统疾病主要是由传染性病原体所引起，但环境因素有很大的影响。相关病原体包括支原体(mycoplasmas)、细菌和病毒(例如Christensen，G.，Sorensen，V.，&Mousing，J.(1999).Diseases of the respiratory system.In Diseases of swine，eds.Straw，B.E.，D’Allaire，S.，Mengeling，W.L.，& Taylor，D.J.，pp.913-940.IowaState University Press，Ames，Iowa.)。
控制猪呼吸系统疾病的最重要措施是改善畜群管理、圈养条件及施行疫苗接种。然而，如猪已显现出呼吸系统疾病，就必须治疗。现行猪呼吸系统疾病的治疗方法包括使用抗生素的治疗。多种抗生素的成功使用已有记载，包括β-内酰胺、喹诺酮及四环素类(例如Lang，I.，Rose，M.，Thomas，E.，& Zschiesche，E.(2002).A field study of cefquinome for the treatment of pigswith respiratory disease.Revue Med Vet 8-9，575-580)。
已知环氧化酶-2(COX-2)在由胸膜肺炎放线杆菌(Actinobacilluspleuropneumoniae)引起的猪的胸膜肺炎的病理生理学中起相关的作用。曝露在胸膜肺炎放线杆菌后，经分离的猪肺泡巨噬细胞增加其COX-2活性(Cho，W.S.& Chae，C.(2003b).In vitro effects of Actinobacillus pleuropneumoniae oninducible nitric oxide synthase and cyclooxygenase-2 in porcine alveolarmacrophages.Am.J Vet Res.64，1514-1518)。此外，原位杂交法(Cho，W.S.&Chae，C.(2003a).Expression of cyclooxygenase-2 in swine naturally infectedwith Actinobacillus pleuropneumoniae，Vet Pathol.40，25-31)和免疫组织化学(Cho，W.S.& Chae，C.(2002).Immunohistochemical detection ofcyclooxygenase-2 in lungs of pigs naturally infected with Actinobacilluspleuropneumoniae.J Comp Pathol.127，274-279)显示在受胸膜肺炎放线杆菌自然感染的猪肺中有增加的COX-2表达。
此外，已知乙酰水杨酸(阿斯匹林)可用来治疗猪的呼吸系统疾病。然而，只有少数受控制的临床研究的信息可获得。文献综述参见Laval，A.(1992)。Utilisation des anti-inflammatoires chez le porc.Rec Méd Vét 168(8/9)，733-744.Ketoprofen，and，to a lesser extent，flunixin decrease fever induced byexperimental infection with Actinobacillus pleuropneumoniae(Swinkels，J.M.，Pijpers，A.，Vernooy，J.C.，Van Nes，A.，& Verheijden，J.H.(1994).Effects ofketoprofen and flunixin in pigs experimentally infected with Actinobacilluspleuropneumoniae.J Vet Pharmacol Ther17，299-303)。然而，并未观察到对于肺部病变的效果。酮洛芬进一步在一对照、盲点临床领域研究中进行测试(De Jong，M.F.，Sampimon，O.，Arnaud，J.P.，Theunissen，G.，Groenland，G.，&Werf，P. J.A clinical study with a non steroid antiinflammatory drug.14，659.1996.IPVS)。在该研究中，酮洛芬在临床评分、复发或治愈率上无效。
吲哚美辛可缓解实验中猪的内毒素诱发性呼吸衰竭(Olson，N.C.，Brown，T.T.，Anderson，J.R.，& Anderson，D.L.(1985).Dexamethasone andindomethacin modify endotoxin-induced respiratory failure in pigs.J.Appl.Physiol.58，274-284)。
美洛昔康是非甾体消炎化合物，其属于昔康类(oxicam class)且具有有效的消炎、抗渗出性及解热活性。美洛昔康作为辅助疗法用于治疗牛的呼吸感染的效力已被广泛证实。最近美洛昔康被核准用于治疗猪的MMA(Hirsch，A.et al.(2003).J Vet Pharmacol Therap 26，355-360)及运动失调(Friton，G.et al.(2003)Berl Münch Tierarztl Wschr 116：421-426)。
一篇文献综述文章(Lees，P.(1991).The pharmacokinetics ofdrugs used inthe treatment of respiratory diseases in cattle and pigs.67-74.Hatfield，U.K.Proc.Royal Vet.Coll.)集中在用于治疗牛和猪的呼吸系统疾病的药物动力学。该公开显示用于猪的非甾体抗炎药数据几乎完全缺乏，且仅列出包括美洛昔康用于牛的数据。
美洛昔康及抗生素共同用于牛呼吸系统疾病已被完整地证实(Schmidt，H.，Philipp，H.，Salomon，E.，& Okkinga，K.(2000).Effekte der zusatzlichenGabe von Metacam(Meloxicam)auf den Krankheitsverlauf bei Rindern mitAtemwegserkrankungen.Der praktische Tierarzt 81，240-244)且在欧盟注册。然而，在猪呼吸系统疾病中使用美洛昔康的信息，至目前为止尚未有公众可得的资料。
由于猪和牛对美洛昔康的药物动力学实质上不同(牛的血浆半衰期为26小时，而猪的为2.5小时)，因此无法预期成功用于牛身上的美洛昔康亦应会对猪有益。
此外，牛和猪呼吸系统疾病的病原体实质上不同。
本发明的基本问题是提供治疗或预防猪呼吸系统疾病(猪养殖中最重要的健康问题之一)的药物。
发明的简要说明
意外地发现美洛昔康可用于治疗或预防猪呼吸系统疾病。
因此，本发明是关于美洛昔康或其可药用的可药用盐在制备用于治疗或预防猪呼吸系统疾病的药物组合物中的用途。
此外，本发明是关于一种治疗或预防猪呼吸系统疾病的方法，该方法包括给药有效量的美洛昔康至需要该治疗的猪。
再者，本发明是关于一种兽药制剂，其包含美洛昔康及至少一种选自β-内酰胺类、喹诺酮类，四环素类、磺酰胺类、氯霉素类(fenicoles)和大环内酯类的抗生素。
本发明另一方面是为治疗或预防猪呼吸系统疾病的即用双组分系统，其中
(a)一种组分，含有美洛昔康和种可药用的载体；和
(b)另一种组分，含有至少一种选自β-内酰胺类、喹诺酮类、四环素类、磺酰胺类、氯霉素类和大环内酯类的抗生素及可药用载体。
又本发明另一方面是一种制品，包括其中含有由美洛昔康和可药用载体组成的组合物的已包装的物质，以及说明所述组合物可用于治疗或预防猪呼吸系统疾病的标签。
附图简单说明
图1以百分比表示首次治疗后发热发生率(直肠温≥40.56℃)，一组猪以土霉素和美洛昔康(◆)治疗，一组单独以土霉素治疗(○)及一组未治疗的对照(△)。
图2表示在研究期第7天和第14天时，饮用水中美洛昔康减轻由实验性猪流感病毒(SIV)感染引起的肺病变的效果。
发明的详细说明
优选地，本发明是关于美洛昔康或其可药用盐在制备用于治疗或预防猪呼吸系统疾病的适合全身或口服给药形式的药物组合物的用途。
下式的美洛昔康(4-羟基-2-甲基-N-(5-甲基-2-噻唑基)-2H-1，2-苯并噻嗪-3-氨甲酰-1，1-二氧化物)
Figure G2005800054227D00041
是一种属于NSAID(非甾体抗炎药物)类的活性物质。美洛昔康及其钠盐和葡甲胺盐(N-甲基-D-葡萄糖胺盐)描述于EP-A-0002482中。
根据本发明，美洛昔康可以生理上可接受的酸加成盐形式使用。根据本发明，生理上可接受的酸加成盐是指葡甲胺盐、钠盐、钾盐或铵盐，优选地为美洛昔康葡甲胺盐。
在另一优选实施方案中，该药物组合物是以符合美洛昔康每日剂量范围0.01mg/kg至5.0mg/kg来给药，优选为0.1mg/kg至3.5mg/kg，特别是0.2至2.0mg/kg。
该药物组合物优选是以适合注射的形式给药，特别是肌肉内注射，或以水溶性颗粒剂形式经由饮用水或作为饲料追肥(top dressing)来给药。
合适的注射制剂公开于例如EP-A-0 002 482的实施例25，其在此引入作为参考。
再者，此种注射溶液可另包含选自柠檬酸、卵磷脂、葡萄糖酸、酒石酸、磷酸及EDTA或其盐类的赋形剂，如公开于国际专利申请WO 01/97813的实施例1至5，在此引入作为参考。
此外，用于无针注射(needleless injection)的美洛昔康注射溶液，公开于国际专利申请WO 03/049733，在此引入作为参考。
用于以经由饮水给药或作为饲料追肥的水溶性颗粒，例如公开于国际专利申请PCT/EP03/11802，在此引入作为参考。
在本发明优选实施方案中，该美洛昔康颗粒剂包含一种粘合剂，其可选自羟丙基-甲基纤维素、聚乙烯吡咯烷酮、明胶、淀粉和聚乙二醇醚，优选为羟丙基-甲基纤维素、聚乙烯吡咯烷酮和聚乙二醇醚，最优选为羟丙基-甲基纤维素和聚乙烯吡咯烷酮。
在本发明的另一优选实施方案中，该美洛昔康颗粒剂包含甜味剂，其可选自糖精钠、阿司帕坦及
Figure G2005800054227D00051
，优选为糖精钠和阿司帕坦。
尤其优选地，根据本发明的美洛昔康颗粒剂包含调味剂，其可选自香草、蜂蜜调味料(honey flavouring)、苹果调味料和contramarum，优选为蜂蜜调味料和苹果调味料。
又尤其优选地，本发明的美洛昔康颗粒剂，其载体是选自乳糖、葡萄糖、甘露醇、木糖醇、蔗糖和山梨糖醇，优选为葡萄糖、乳糖或山梨糖醇，更优选为葡萄糖或乳糖，最优选为葡萄糖。
最优选的是下列的美洛昔康颗粒剂：
实施例A
0.6％美洛昔康颗粒
配方：
                      g/100g
美洛昔康              0.6
葡甲胺                0.42
羟丙基甲基纤维素      3.00
聚乙烯吡咯酮          2.00
单水合葡萄糖          93.98
实施例B
1.2％美洛昔康颗粒
美洛昔康                1.2
葡甲胺                  0.84
羟丙基甲基纤维素        3.00
Collidone 25            2.00
单水合葡萄糖            92.96
实施例C
0.6％美洛昔康颗粒
美洛昔康                0.6
葡甲胺                  0.42
Pharmacoat 606          4.0
聚乙二醇6000            1.0
乙酰舒泛K               0.3
乳糖                    93.68
实施例D
0.6％美洛昔康颗粒剂
美洛昔康                0.6
葡甲胺                  0.42
Pharmacoat 606          4.75
聚乙二醇6000            0.25
乙酰舒泛K               0.3
液体香草调味料          0.05
乳糖                    93.63
尤其优选地，美洛昔康颗粒剂中的美洛昔康含量是介于0.05％和4％之间，优选是介于0.1和2％之间、优选是介于0.3％和1.8％之间，更优选是介于0.4％和1.5％之间，最优选是1.2％。又尤其优选地，美洛昔康颗粒剂含有葡甲胺与美洛昔康的摩尔比为约9∶8至12∶8，优选为10∶8。
根据本发明美洛昔康可用于治疗任何品种猪的呼吸系统疾病。优选地，猪选自美国长白猪(American Landrace)、美国约克郡猪(American Yorkshire)、安吉恩山多贝猪(Angeln Saddleback)、啊帕瓦岛猪(Arapawa Island)、巴川猪(Ba Xuyen)、班图猪(Bantu)、巴兹那猪(Bazna)、北京黑猪(Beijing Black)、白俄罗斯黑杂色猪(Belarus Black Pied)、比利时长白猪(Belgian Landrace)、贝恩特海姆黑杂色猪(Bentheim Balck Pied)、伯克郡猪(Berkshire)、黑斯洛文尼亚猪(Black Slavonian)、英国长白猪(British Landrace)、英国垂耳猪(British Lop)、保加利亚白猪(Bulgarian White)、广东猪(Cantonese)、赤斯特白猪(Chester White)、捷克改良白猪(Czech Improved White)、丹麦长白猪(Danish Landrace)、杂色猪(Dermantsi Pied)、杜洛克猪(Duroc)、荷兰长白猪(Dutch Landrace)、风泾猪(Fengjing)、芬兰长白猪(Finnish Landrace)、法国长白猪(French Landrace)、德国长白猪(German Landrace)、格洛斯特郡老区猪(Gloucestershire Old Spots)、几内亚阉猪(Guinea Hog)、汉普郡猪(Hampshire)、赫里福德猪(Hereford)、黑左猪(Hezuo)、伊布里安猪(Iberian)、意大利长白猪(Italian Landrace)、金华猪(Jinhua)、卡拉猪(Kele)、克斯烤普捷猪(Krskopolie)、库内昆猪(Kunekune)、拉孔布猪(Lacombe)、大型黑猪(Large Black)、大型黑白猪(Large Black-white)、大型白猪(Large White)、立陶宛土猪(Lithuanian Native)、曼格丽萨猪(Mangalitsa)、眉山猪(Meishan)、中型白猪(Middle White)、民主镇猪(Minzhu)、芒街猪(Mong Cai)、木克塔猪(Mukota)、莫拉罗曼哥拉猪(Mora Romagnola)、蒙雷猪(Moura)、并蹄猪(Mulefoot)、内江猪(Neijiang)、宁乡猪(Ningxiang)、挪威长白猪(Norwegian Landrace)、奥萨堡岛猪(Ossabaw Island)、牛津沙猪和黑猪(Oxford Sandy and Black)、菲律宾土猪(Philippine Native)、皮特兰猪(Pietrain)、波兰中国猪(Poland China)、红金合欢猪(Red Wattle)、山多贝猪(Saddleback)、斯波兹猪(Spots)、斯瓦比亚庄园猪(Swabian-Hall)、瑞典长白猪(Swedish Landrace)、塔姆沃思猪(Tanworth)、尺饶猪(Thuoc Nhieu)、西藏猪(Tibetan)、图鲁普捷猪(Turopolje)，越南大肚猪(Vietnamese Potbelly)，威尔士猪(Welsh)和五指山猪(Wuzhishan)的猪种，特别是，美国长白猪、比利时长白猪、英国长白猪、丹麦长白猪、荷兰长白猪、芬兰长白猪、法国长白猪、德国长白猪、意大利长白猪和皮特兰猪可用根据本发明的美洛昔康治疗。
更优选地，美洛昔康是与抗生素共同给药，优选的抗生素选自β-内酰胺类、喹诺酮类，四环素类、磺酰胺类、氯霉素类和大环内酯类。
最优选的是阿莫西林、土霉素、氟砜尼可(florfenicol)、泰洛星(tylosin)、替米考星(tilmicosin)及磺胺二甲嘧啶。
抗生素的剂量本身并不限制，且强烈地依据所使用抗生素的不同效力而定。通常至多150.0mg/kg，优选是自0.1mg/kg至120mg/kg，特别是自10mg/kg至110mg/kg的抗生素与美洛昔康共同给药。
下列剂量范围是最优选的：
阿莫西林：5至30mg/kg，特别是约10mg/kg，
土霉素：  20至70mg/kg，特别是约30mg/kg，
氟砜尼可：10至20mg/kg，特别是约15mg/kg，
泰洛星：  10至25mg/kg，特别是约16mg/kg，
替米考星：5至30mg/kg，特别是10至20mg/kg，
磺胺二甲嘧啶：80至150mg/kg，特别是约100mg/kg。
术语“共同给药”(或“与...共同给药”)，在美洛昔康和抗生素限制使用中，指包含以顺序用药方式给药各药剂的，其可提供有益效果，特别是药物组合对已患病的猪呼的吸道疾病的症状的减轻。该术语还包含以基本上同时方式的这些药物共同给药，例如以含有固定比例的这些活性药剂的单一胶囊或注射溶液，或以每种药剂的多个、单独的胶囊。
因此，美洛昔康和抗生素可以组合形式，或单独地或单独且顺序地共同给药，其中该顺序给药优选是时间上接近。
优选地，根据本发明的药物是用于预防或治疗成长或养肥中猪的呼吸系统疾病征(Porcine Respiratory Disease Complex)；或
用于预防或治疗由支原体引起的猪的呼吸系统疾病，所述的细菌特别是猪肺炎支原体(Mycoplasma hyopneumoniaw)、猪鼻支原体(Mycoplasmahyorhinis)；
用于预防或治疗由细菌引起的猪呼吸系统疾病，特别是放线杆菌属(Actinobacillus spp.)，特别是胸膜肺炎放线杆菌(Actinobacilluspleuropneumoniae)、支气管炎博德特氏菌(Bordetella bronchiseptica)、多杀巴斯德氏菌(Pasteurella multocida)、化脓隐秘杆菌(Arcanobacterium pyogenes)、链球菌属(Streptococcus spp.)，及葡萄球菌属(Staphylococcus spp.)；或
用于预防或治疗由病毒引起的猪呼吸系统疾病，所述病毒特别是猪流感病毒(Swine Influenza Virus)、阿兹克(Aujetzky’s)病毒、猪生殖与呼吸综合征病毒(Porcine Reproductive and Respiratory Syndrome)、猪环病毒(Porcinecircovirus)、及传染性肠胃炎(Transmissible Gastroenteritis)和猪呼吸系统冠状病毒。
最优选地，根据本发明的药物是用于预防或治疗由肺炎支原体、胸膜肺炎放线杆菌、多杀巴斯德氏菌、猪链球菌、猪流感病毒、猪生殖与综合征病毒所引起的猪呼吸系统疾病。
下列实施例用于阐述根据本发明的美洛昔康的用途。仅欲以实施例的形式描述可能的技术，而非限制本发明的内容。
实施例1
美洛昔康对实验性胸膜肺炎放线杆菌感染的猪的效力
该研究是在平行组设计实验条件下的对照的、随机的、盲的探察研究。
约10周龄的杂交猪用胸膜肺炎放线杆菌的单一鼻内接种进行激发。下一天，如猪满足下列包括的标准，则纳入于本研究中并予以治疗：肛温≥40℃且出现急性或亚急性感染性呼吸系统疾病的临床症状。
二十四头猪(12头阉割公猪和12头母猪)被纳入且随机分配在三个治疗组中，每组8头。该治疗组是：
  组   治疗
  1   未治疗
  2   土霉素
  3   土霉素和美洛昔康
美洛昔康以0.5％溶液给药，连续三日每日0.5mg/kg，土霉素以20％长效溶液(200)以20mg/kg单剂量注射。
效力评估的相关标准为发热发生率、呼吸系统疾病的临床参数、死亡及首次治疗10天后或自然死亡后尸检出现肺损伤。受损伤肺部组织的百分比是以肺叶计算并以整个肺部平均。
用胸膜肺炎放线杆菌激发，在12小时内产生重症胸膜肺炎。
首次治疗后的发热发生率(肛温≥40.56℃)中，第3组(◆)低于第1组(△)和第2组(○)(参见图1)。
临床参数中最佳治疗反应在第3组中观察到。
首次治疗后3日间猪死亡数量如下所示：
  组(n＝8每组)   死亡
  1   7
  2   1
  3   0
第3组中平均肺损伤的范围较其他组别不严重(见下)。
  组   肺损伤(％)
  1   60
  2   35
  3   14
除抗生素治疗外，美洛昔康有效地减缓了在实验性胸膜肺炎放线杆菌感染猪的发热、呼吸系统疾病临床症状、死亡及肺部病变范围。
实施例2
饮水中的美洛昔康对以实验性猪流感病毒感染的猪的效力
本研究的目的是测试溶于饮水中的美洛昔康颗粒对实验性感染猪流感病毒(SIV)的猪的效力。
本研究是开放的、阴性对照随机的实验室研究，其根据GPC在单点进行。
每克含6mg美洛昔康的美洛昔康颗粒是在连续7日内，随意地经由浓度为每升饮水1克颗粒的饮水给药治疗组(A+B)中的猪。其导致实际的美洛昔康摄取为每日每kg体重0.8mg。在对照组(C)中的猪是随意饮用自来水。
在第0研究日，30头猪感染SIV。10头猪分配在三组A、B和C的各组中。同一日，A组和B组的治疗在SIV激发后开始。
该研究动物在第0至7和第14研究日每日进行临床检查。这些动物在第7和14研究日称重。A组的所有动物及C组的5只动物在第7研究日施以安乐死及解剖，其余的研究动物-B组和C组5只研究动物-在第14研究日施以安乐死及解剖。
本研究的主要发现是美洛昔康颗粒以体重计大约每日剂量为0.8mg/kg连续投予于饮水中，可显著地减缓在激发后第一周内由SIV实验性感染引起的肺损伤的发展。图2显示了第7和14研究日时以肺叶计算的肺损伤数量。
在第7研究日，美洛昔康组A的由SIV相关损伤影响的肺组织百分比(平均值)为8.9％，对照组(C组的5只研究动物)为23.8％。
此外，相较于未治疗对照组，用美洛昔康治疗的猪在感染后两周内体重显著增加。在间隔研究日(interval study day)第0到第7日，美洛昔康组A的平均每日体重增加是557克，对照组(C组中5只动物)为257克。在间隔研究日第0至14日的间隔研究中，美洛昔康B组的平均每日体重增加是629克，对照组(C组中5只动物)为486克。在临床指数分数(CIS)曲线下的区域，是相关临床参数的总和，在研究日第0至7日，A组和B组显著小于C组。
因此，用美洛昔康颗粒连续7日以每日剂量为每千克体重0.8mg的美洛昔康口服治疗是SIV感染的有效治疗。
实施例3
关于美洛昔康对成长/养肥中猪的呼吸系统疾病综合症(PRDC)效果的现场试验
材料和方法
选择一个中等规模(560只猪)、有PRDC复发史的农场。选择162只平均龄期为90日、有PRDC发作临床征兆的成长中动物进行双盲随机研究。将动物根据相同的性别比率、相同圈舍和饲养条件及遗传背景随机分配到8个圈且分成两个治疗组。第1组(PC)从第0天(d0)(试验开始，n＝82)开始于饲料中连续8日接受800ppm金霉素，外加安慰剂的单独IM注射(等张生理盐水)。第2组(M)从第0天开始于饲料中连续8日接受800ppm金霉素，外加0.4mg/kg体重美洛昔康(2％美他康
Figure G2005800054227D00111
)，Boehringer IngelheimGmbH)的单独IM注射。临床参数以在连续8日中利用3分评分法(0＝没有征兆，至3＝腹式呼吸和紊乱的一般情况)的每日呼吸分数(RS)，及额外所需的可注射药物(AIM)的总数来评定。每组生长的特性数据包括下列试验期间的平均每日增长(Average Daily Gain)(ADG)：龄期为第90至第117天、第117至第170天(宰杀)及第90至第170天。亦计算这些期间的死亡率。每组的屠宰记录，包括每个肺部表面(LS)被慢性和急性呼吸系统损伤影响的百分比。
Student’s t-Test及Pearson’s Chi-Square Test用于试验组之间的平均值和频率的结果比较。
结果和讨论
与对照组相比，美洛昔康组中的RS和AIM显著低(p＜0.05)。
由急性损伤影响的LS的结果相同(P＜0.01)，而慢性病例中的LS没有观察到差异(表1)。
该生长特性数据的分析在各组之间在第90至第117天(p＜0.05，表2)显示出显著的差异。
表1 RS，LS：平均(SD)；AIM数(％)
Figure G2005800054227D00121
a，b每行中有不同上标的值显著地不同
表2 ADG：平均(SD)
表3 死亡率：动物数目/组(％)
Figure G2005800054227D00123
a，b每列中有不同上标的值显著地不同(p＜0.05；表2和3)
在本研究的条件下，呼吸系统症状流行率的降低及所需注射抗生素药剂的总数的减少，表示美洛昔康的有效抗炎活性。后者可为一种有用的辅助方法，特别当呼吸系统窘迫与饲料摄取量显著减少有关联时。生长特性和死亡率的初始差异，可解释为，当美洛昔康和适当的抗生素治疗组合时，可使受影响的动物自呼吸系统炎症更快痊愈和失调的生长率更快恢复。还需要评估饲料摄取量及将美洛昔康用于PRDC复发状况的进一步研究。

Claims (11)

1.美洛昔康或其可药用盐在制备用于治疗或预防由猪呼吸系统疾病综合征、猪流感病毒和胸膜肺炎放线杆菌引起的猪呼吸系统疾病的药物组合物中的用途。
2.根据权利要求1的用途，其特征在于该药物组合物是适用于全身或口服给药的形式。
3.根据权利要求1或2的用途，其特征在于该药物组合物是以0.01mg/kg到5.0mg/kg的每日剂量给药。
4.根据权利要求1至3任一项的用途，其特征在于该药物组合物是适用于注射的形式或为经由饮水或作为饲料追肥给药的可溶性颗粒剂形式。
5.根据权利要求1至4任一项的用途，其特征在于该美洛昔康与四环素类共同给药。
6.根据权利要求1至5任一项的用途，其特征在于该美洛昔康与土霉素和金霉素共同给药。
7.根据权利要求1至6任一项的用途，其特征在于该药剂用于预防或治疗成长中或养肥猪的猪呼吸系统疾病综合征。
8.根据权利要求1至7任一项的用途，其特征在于该药剂用于预防或治疗由胸膜肺炎放线杆菌、猪流感病毒和猪呼吸系统疾病综合征引起的猪呼吸系统疾病。
9.治疗猪呼吸系统疾病的即用双组分系统，其中，
(a)一种组分，含有美洛昔康和可药用的载体；和
(b)另一种组分，含有至少一种选自四环素类的抗生素及可药用的载体。
10.一种制品，包括其中含有由美洛昔康和可药用的载体所组成的组合物的已包装的物质，以及说明所述组合物可用于治疗或预防由猪呼吸系统疾病综合征、猪流感病毒和胸膜肺炎放线杆菌引起的猪呼吸系统疾病的标签。
11.即用双组分系统在制备用于治疗猪呼吸系统疾病的药物组合物中的用途，其中，
(a)一种组分，含有美洛昔康和可药用的载体；和
(b)另一种组分，含有至少一种选自四环素类的抗生素及可药用的载体。
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