CN105770779A - 一种防治牛传染性胸膜肺炎的药物组合物及其制备方法 - Google Patents
一种防治牛传染性胸膜肺炎的药物组合物及其制备方法 Download PDFInfo
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Abstract
本发明公开了一种防治牛传染性胸膜肺炎的药物组合物及其制备方法,其药物组合物包括以下原料药材:素馨花、红头小仙、阿利藤、柴胡、假蒟果穗、雪灵芝、地皮消、降真香、兰石草、苤蓝叶、露水草、款冬花、排骨灵、绿绒蒿、桂叶素馨、蓬莪术、佛手露、梵天花、戟叶石苇、芥子、竻慈姑和紫花景天。本发明的有益效果是:本发明的药物组合物在防治牛传染性胸膜肺炎中,具有抗菌消炎,理气健胃的作用,在一定程度上增强牛的免疫力,具有治愈率高,见效快,治疗疗程短,无毒副作用等优势。
Description
技术领域
本发明涉及兽药领域,特别涉及一种防治牛传染性胸膜肺炎的药物组合物及其制备方法。
背景技术
牛传染性胸膜肺炎(又称牛肺疫)是由支原体感染引起的一种高度接触性传染病,以渗出性纤维素性肺炎和浆液纤维素性胸膜肺炎为特征。牛传染性胸膜肺炎潜伏期2-4周。病原体为丝状支原体,过去经常用的名称为类胸膜肺炎微生物(PPLO),支原体多形,可呈球菌样、丝状、螺旋体与颗粒状。细胞的基本形状以球菌样为主,革兰氏染色阴性。本菌在加有血清的肉汤琼脂可生长成典型菌落。支原体对外界环境因素抵抗力不强。暴露在空气中,特别在直射日光下,几小时即失去毒力。干燥、高温都可使其迅速死亡,但在病肺组织冻结状态,能保持毒力1年以上,培养物冻干可保存毒力数年,对化学消毒药抵抗力不强,对青霉素和磺胺类药物、龙胆紫则有抵抗力。本病易感动物主要是牦牛、奶牛、黄牛、水牛、犏牛。各种牛对本病的易感性,依其品种、生活方式及个体抵抗力不同而有区别,发病率为60%-70%,病死率约30%-50%。主要传染源是病牛及带菌牛。病牛康复15个月甚至2-3年后还能感染健牛。病原体主要由呼吸道随飞沫排出,也可由尿及乳汁排出,在产犊时还可由子宫渗出物中排出。自然感染主要传播途径是呼吸道。当传染源进入健康牛群时,咳出的飞沫首先被邻近牛只吸人而感染,再由新传染源逐渐扩散。通过被病牛尿污染的饲料、干草,牛可经口感染。年龄、性别、季节和气候等因素对易感性无影响。饲养管理条件差、畜舍拥挤,可以促进本病的流行。牛群中流行本病时,流行过程常拖延甚久。舍饲者一般在数周后病情逐渐明显,全群患病要经过数月。带菌牛进人易感牛群,常引起本病的急性暴发,以后转为地方性流行。
临床症状:潜伏期为2-4周,短则8d,长可达4个月。症状发展缓慢者,常是在清晨冷空气或冷饮刺激或运动时,发生短干咳嗽,初始咳嗽次数不多而逐渐增多,继之食欲减退,反刍迟缓,泌乳减少,此症状易被忽视。症状发展迅速者则以体温升高0.5-1℃开始。随病程发展,症状逐渐明显。按其经过可分为急性和慢性两型。
急性型症状明显而有特征性,体温升高到40-42℃,呈稽留热,干咳,呼吸加快而有呻吟声,鼻孔扩张,前肢外展,呼吸极度困难。由于胸部疼痛不愿行动或下卧,呈腹式呼吸。咳嗽逐渐频繁,常是带有疼痛短咳,咳声弱而无力,低沉而潮湿。有时流出浆液性或脓性鼻液,可视黏膜发绀。呼吸困难加重后,叩诊胸部,患侧肩胛骨后有浊音或实音区,上界为一水平线或微凸曲线。听诊患部,可听到湿性罗音,肺泡音减弱乃至消失,代之以支气管呼吸音,无病变部分则呼吸音增强,有胸膜炎发生时,则可听到摩擦音,叩诊可引起疼痛。病后期,心脏常衰弱;脉搏细弱而快,每分钟可达80-120次,有时因胸腔积液,只能听到微弱心音或不能听到。此外还可见到胸下部及肉垂水肿,食欲丧失,泌乳停止,尿量减少而比重增加,便秘与腹泻交替出现。病畜体况迅速衰弱,眼球下陷,眼无神,呼吸更加困难,常因窒息而死。急性病程一般在症状明显后经过5-8d,约半数取死亡,有些患畜病势趋于静止,全身状态改善,体温下降、逐渐痊愈。有些患畜则转为慢性,整个急性病程约为15-60d。
慢性型多数由急性转来,也有开始即取慢性经过者。除体况消瘦,多数无明显症状。偶发干性短咳,叩诊胸部可能有实音区。消化机能扰乱,食欲反复无常,此种患畜在良好护理及妥善治疗下,可以逐渐恢复,但常成为带菌者。若病变区域广泛,则患畜日益衰弱,预后不良。
病理变化:特征性病变主要在胸腔。典型病例是大理石样肺和浆液纤维素性胸膜肺炎。肺和胸膜的变化,按发生发展过程,分为初期、中期和后期三个时期。初期病变以小叶性支气管肺炎为特征。肺炎灶充血、水肿,呈鲜红色或紫红色。中期呈浆液性纤维素性胸膜肺炎,病肺肿大、增重,灰白色,多为一侧性,以右侧较多,多发生在膈叶,也有在心叶或尖叶者。切面有奇特的图案色彩,犹如多色的大理石,这种变化是由于肺实质呈不同时期的改变所致。肺间质水肿变宽,呈灰白色,淋巴管扩张,也可见到坏死灶。胸膜增厚,表面有纤维素性附着物,多数病例的胸腔内积有淡黄透明或混浊液体,多的可达10000-20000ml,内混有纤维素凝块或凝片。胸膜常见有出血,肥厚,并与肺病部粘连,肺膜表面有纤维素附着物,心包膜也有同样变化,心包内有积液,心肌脂肪变性。肝、脾、肾无特殊变化,胆囊肿大。后期,肺部病灶坏死,被结缔组织包围,有的坏死组织崩解(液化),形成脓腔或空洞,有的病灶完全瘢痕化。本病病变还可见腹膜炎、浆液性纤维性关节炎等。
诊断:本病初期不易诊断,若引进种牛仔数周内出现高热,持续不退,同时兼有浆液性纤维素胸膜肺炎之症状
根据流行病学资料、临床症状及病理变化各方面综合诊断。如有典型胸腔病变,则结合流行病学资料及临床症状常可并结合病理变化可作出初步诊断。进一步诊断可结合补体结合反应。其病理诊断要点为:1、肺呈多彩色的大理石样变;2、肺间质明显增宽、水肿,肺组织坏死;3、浆液纤维素性胸膜肺炎。牛肺疫与牛巴氏病:后者发病急、病程短,有败血症表现,组织和内脏有出血点;肺病变大理石样变及间质增宽不明显。早期牛肺疫与结核病鉴别:应通过变态反应及血清学实验等区别。
做出初步诊断。确诊有赖于血清学检查和细菌学检查。本病常用的血清学检查方法为补体结合试验。也可应用凝集反应试验,此法操作较简便,但因凝集素在病牛体内持续时间短,故其准确性不如补体结合试验。在本病疫区,也有应用间接血凝。试验、玻片凝集试验作为辅助诊断之用者。细菌学检查时,取肺组织、胸腔渗出液及淋巴结等接种于10%马血清马丁肉汤及马丁琼脂,37℃培养2~7d,如有生长,即可进行支原体的鉴定。
防治:非疫区忽从疫区引牛。老疫区宜定期用牛肺疫兔化弱毒菌苗及防注射;发现病牛应隔离、封锁,必要时宰杀淘汰;污染的牛舍、屠宰场应用3%来苏儿或20%石灰乳消毒。本病早期治疗可达到临床治愈。病牛症状消失,肺部病灶被结缔组织包裹或钙化,但长期带菌,应隔离饲养以防传染。具体措施:1、“九一四”疗法,肉牛3-4克“九一四”溶于5%葡萄糖盐水或生理盐水100-500毫升中,一次静脉注射,间隔5日一次,连用2-4次,现用现配;2、抗生素治疗,四环素或土霉素2-3克,每日一次,连用5-7日,静注;链霉素3-6克,每日一次,连用5-7日,除此之外辅以强心,健胃等对症治疗。
西医治疗牛传染性胸膜肺炎方案单一,疗程较长、临床效果不明显,甚至可能因此延误病情、扩大病牛传染范围。并且,长期应用化学合成药物毒副作用大、药物残留量较高,消费者食用此类牛肉对其机体免疫力产生。
但是,中医药不仅具有西药的优势,并且治愈率高,无污染,可抗菌、消炎,增强牛免疫力,治愈后不易复发,成本价个低廉,在牛传染性胸膜肺炎方面,具有十分重要的现实及临床意义。
发明内容
本发明所要解决的技术问题是在于提供一种防治牛传染性胸膜肺炎的药物组合物,本发明的药物组合物在防治牛传染性胸膜肺炎中,具有抗菌消炎,理气健胃的作用,在一定程度上增强牛的免疫力,具有治愈率高,见效快,治疗疗程短,无毒副作用等优势。
为了实现上述发明目的,本发明提供了一种防治牛传染性胸膜肺炎的药物组合物,所述药物组合物包括以下原料药材:素馨花、红头小仙、雪灵芝、地皮消、降真香、兰石草、苤蓝叶、露水草、款冬花、绿绒蒿、桂叶素馨、蓬莪术、佛手露、梵天花、戟叶石苇、芥子、竻慈姑和紫花景天。
所述药物组合物中各原料药材的重量份数比为:素馨花15-25重量份、红头小仙9-18重量份、雪灵芝15-35重量份、地皮消13-27重量份、降真香11-31重量份、兰石草14-26重量份、苤蓝叶15-35重量份、露水草9-18重量份、款冬花12-24重量份、绿绒蒿2-4重量份、桂叶素馨11-21重量份、蓬莪术14-36重量份、佛手露11-24重量份、梵天花10-30重量份、戟叶石苇12-22重量份、芥子15-35重量份、竻慈姑13-31重量份和紫花景天15-25重量份。
所述药物组合物中各原料药材的重量份数比为:素馨花22重量份、红头小仙14重量份、雪灵芝32重量份、地皮消24重量份、降真香30重量份、兰石草25重量份、苤蓝叶35重量份、露水草16重量份、款冬花22重量份、绿绒蒿3重量份、桂叶素馨20重量份、蓬莪术32重量份、佛手露20重量份、梵天花30重量份、戟叶石苇14重量份、芥子33重量份、竻慈姑27重量份和紫花景天21重量份。
所述药物组合物还包括:阿利藤、柴胡、假蒟果穗和排骨灵。
所述药物组合物中各原料药材的重量份数为:素馨花15-25重量份、红头小仙9-18重量份、雪灵芝15-35重量份、地皮消13-27重量份、降真香11-31重量份、兰石草14-26重量份、苤蓝叶15-35重量份、露水草9-18重量份、款冬花12-24重量份、绿绒蒿2-4重量份、桂叶素馨11-21重量份、蓬莪术14-36重量份、佛手露11-24重量份、梵天花10-30重量份、戟叶石苇12-22重量份、芥子15-35重量份、竻慈姑13-31重量份、紫花景天15-25重量份、阿利藤3-5重量份、柴胡10-30重量份、假蒟果穗15-25重量份和排骨灵10-20重量份。
所述药物组合物中各原料药材的重量份数为:素馨花22重量份、红头小仙14重量份、雪灵芝32重量份、地皮消24重量份、降真香30重量份、兰石草25重量份、苤蓝叶35重量份、露水草16重量份、款冬花22重量份、绿绒蒿3重量份、桂叶素馨20重量份、蓬莪术32重量份、佛手露20重量份、梵天花30重量份、戟叶石苇14重量份、芥子33重量份、竻慈姑27重量份、紫花景天21重量份、阿利藤3重量份、柴胡12重量份、假蒟果穗23重量份和排骨灵15重量份。
所述药物组合物的剂型为粉针剂,其制备方法包括以下步骤:
第一步,将所述原料药材按比例混合,放入超微粉碎机中粉碎成0.1~10μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第二步,在第一步获得的混合粉料中加入相对于所述混合粉料的质量3~5倍的醇浓度为85%~95%的乙醇,搅拌溶解获得乙醇溶液,将乙醇溶液在5℃~10℃的条件下静置24~36小时,采用渗漉法以每分钟1~2ml的速度缓缓渗漉,收集渗漉液,浓缩并干燥,并在此放入超微粉碎机中粉碎40~60分钟,获得0.1~10μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第三步,取第二步获得的混合粉料10g~20g,加入丙二醇30g~50g,加200ml注射用水,搅拌使其溶解,进一步加注射用水至1000ml,再加入1g~1.5g针用活性炭,充分搅拌30~50分钟;脱炭过滤;用0.22~0.24μm微孔滤膜过滤;冷冻干燥得无菌粉末,分装灌封。
所述药物组合物的剂型为散剂,其制备方法包括以下步骤:
第一步,将地皮消、降真香、兰石草、苤蓝叶和露水草按所述比例混合,用相对于获得的混合物质量的3~5倍的醇浓度为85%~95%的乙醇溶解,加热回流2~4小时后提取,过滤,得第一过滤液;将滤渣再次用相对于获得的混合物质量的1~2倍的醇浓度85%~95%的乙醇溶解,加热回流1~2小时后提取,过滤,得第二过滤液;合并第一过滤液和第二过滤液,减压回收乙醇并浓缩至药液浓度为0.7~0.9g生药/mL,经体积为5L的大孔吸附树脂柱洗脱,先用5倍树脂柱体积的去离子水或蒸馏水洗脱,再用3倍树脂柱体积的醇浓度为90%~95%乙醇洗脱,收集乙醇洗脱液,减压浓缩除去乙醇,干燥并粉碎成粉末;
第二步,将梵天花、戟叶石苇、芥子、竻慈姑和紫花景天按所述比例混合,加相对于获得的混合物质量的2~4倍的醇浓度85%~95%的乙醇,加热回流提取1~2次,提取液合并,用管式离心机离心除杂,将除杂后的提取液于60℃~70℃的条件下减压浓缩至60℃时相对密度为1.20~1.23的膏体,将浓缩后的膏体用喷雾干燥器干燥成粉末;
第三步,将剩余原料药材按所述比例混合,加相对于获得的混合物质量的2~4倍的水溶解,加热煎煮2~4小时,过滤;将滤渣再次用相对于获得的混合物质量的1~2倍的水溶解,再次加热煎煮1~2小时,过滤;合并两次的过滤液,减压浓缩除去水分,干燥并粉碎成粉末;
第四步,将第一步、第二步和第三步获得的粉末混合,随后过筛成80~120目的细粉,将获得的细粉投入混合搅拌机中搅拌,即获得散剂。
本发明的有益效果是:本发明的药物组合物在防治牛传染性胸膜肺炎中,具有抗菌消炎,理气健胃的作用,在一定程度上增强牛的免疫力,具有治愈率高,见效快,治疗疗程短,无毒副作用等优势。
具体实施方式
本发明提供了一种防治牛传染性胸膜肺炎的药物组合物,包括以下原料药材:素馨花、红头小仙、阿利藤、柴胡、假蒟果穗、雪灵芝、地皮消、降真香、兰石草、苤蓝叶、露水草、款冬花、排骨灵、绿绒蒿、桂叶素馨、蓬莪术、佛手露、梵天花、戟叶石苇、芥子、竻慈姑和紫花景天。
上述各原料药材的药理特性如下:
紫花景天:别名:石蝴蝶、蟑螂头、丁字草、丁拔、尖叶脚疔草、活血丹。来源:景天科紫花景天SedummingjinianumFu,以全草入药。性味:苦,凉。主治:活血生肌,止血解毒。主治挫伤,小儿惊风,胸膜炎,吐血,毒蛇咬伤,腰肌劳损,烫伤,带状疱疹。
芥子:别名:白芥子、黄芥子、芥菜子、青菜子。来源:本品为十字花科植物白芥SinapisalbaL.或芥Brassicajuncea(L.)Czern.etCoss.的干燥成熟种子。前者习称“白芥子”,后者习称“黄芥子”。夏末秋初果实成熟时采割植株,晒干,打下种子,除去杂质。性味:辛,温。归经:归肺经。主治:温肺豁痰利气,散结通络止痛。用于寒痰喘咳,胸胁胀痛,痰滞经络,关节麻木、疼痛,痰湿流注,阴疽肿毒。
雪灵芝:出处:《民间常用草药汇编》。来源:为石竹科植物甘肃蚤缀的全草。夏季采全草,晒干。性味:《高原中草药治疗手册》:"微甘,凉。"归经:《高原中草药治疗手册》:"入肝、胆、脾经。"主:治流感,肺炎,黄疸,筋骨疼痛,淋病。①《民间常用草药汇编》:"治淋、浊症,止咳。"②《高原中草药治疗手册》:"清热解毒,利胆除黄。治流感,肺炎,筋骨疼痛。"
绿绒蒿:出处:《高原中草药治疗手册》。别名:阿拍色鲁(藏名)。来源:为罂粟科植物全缘绿绒蒿的花、果实或全草。7~8月采收花、果实或全草(除去毛刺),洗净,晒干。性味:①《西藏常用中草药》:"甘涩,寒,有小毒。"②《高原中草药治疗手册》:"苦涩,微寒,有小毒。"归经:《高原中草药治疗手册》:"入肝、肾、大肠经。"主治:清热利湿,镇咳平喘。治肺炎咳嗽,肝炎,胆绞痛,胃肠炎,湿热水肿,白带,痛经。①《西藏常用中草药》:"清热泄肺,除湿利水。治咳嗽,肺炎,肝炎,湿热水肿。"②《高原中草药治疗手册》:"镇静止痛,镇咳平喘,制痢止血。治胃肠发炎,肝炎,胆痛,白带,痛经。"
柴胡:来源:本品为伞形科植物柴胡BupleurumchinenseDC.或狭叶柴胡BupleurumscorzonerifoliumWilld.的干燥根。按性状不同,分别习称“北柴胡”及“南柴胡”。春、秋二季采挖,除去茎叶及泥沙,干燥。性味:苦,微寒。归经:归肝、胆经。主治:和解表里,疏肝,升阳。用于感冒发热,寒热往来,胸胁胀痛,月经不调,子官脱垂,脱肛。
红头小仙:出处:《昆明民间常用草药》。别名:毛干药、甲冬仗、那猪草(《广西药枝名录》),紫背倒提壶(《昆明民间常用草药》)。来源:为菊科植物毛艾纳香的全草。春季采收,洗净,鲜用或晒干研粉备用。性味:《昆明民间常用草药》:"微苦,平。"主治:清热,化痰止咳。治风热咳喘,头痛,鼻渊,胸膜炎,乳腺炎。①《广西药植名录》:"止咳,消痰。治头痛,鼻渊,皮肤干燥。"②《昆明民间常用草药》:"消炎,退烧。治春温风热,肺炎,喘咳,胸膜炎,乳腺炎。"
露水草:别名:珍珠露水草、换肺散、鸡冠参、蓝耳草、蛛毛蓝耳草、蛛丝毛蓝耳草。来源:鸭跖草科蓝耳草属植物露水草CyanotisarachnoidesC.B.Clarke,以根入药。夏秋采集,洗净,鲜用或晒干。性味:甘,平。主治:祛风活络,利湿消肿,退虚弱。用于风湿性关节炎,腰腿痛,肾炎水肿,虚热不退;外用治湿疹,脚癣,刀伤。梵天花:出处:《福建民间草药》。别名:三角枫、三合枫(《植物名实图考》),藕头婆(《广州植物志》),犬跤迹、犬跤爪,野茄、破布勒、假肉花、虱麻头(《福建民间草药》),五龙会、粘花衣、假棉花(《闽东本草》),野棉花、野棉桃(《江西民间草药验方》),地棉花、八大锤、七姐妹(《江西草药》),山棉花、棉花肾、狗脚迹、红野棉花、野木棉(《浙江民间常用草药》),乌云盖雪(《广西中草药》)。来源:为锦葵科植物梵天花的全草。夏、秋采,去根,晒干。性味:①《福建民间草药》:"甘,温。"②《广西实用中草药新选》:"味淡微甘,性凉。"主治:祛风解毒。治痢疾,疮疡,风毒流注,毒蛇咬伤。《广西实用中草药新选》:"消炎消肿,凉血解毒。主治痢疾,腹泻,疖肿,狂犬病,毒蛇咬伤。"
佛手露:出处:《纲目拾遗》。来源:为芸香种植物佛手的果实的蒸馏液。性味:《纲目拾遗》:"味淡。"主治:①《金氏药帖》:"专治气膈,解郁,大能宽胸。"②《中国医学大辞典》:"悦脾,舒肝,宽胸,解郁,疏气,开胃进食。治气膈,烦热骨蒸。"
兰石草:来源:玄参科兰石草属植物兰石草LanceatibeticaHook.f.etThoms.的全草,其果实亦入药。7~9月采集全草,洗净晒干。9~10月采摘果实,晒干。性味:甘、苦,寒。主治:清肺祛痰、解毒。全草:用于肺热咳嗽,肺脓疡;果实:月经不调,下腹疼痛,便秘。
地皮消:出处:《云南中草药选》。别名:地皮胶、刀口药、蛆药(《云南中草药》)。来源:为爵床科植物喜栎小苞爵床的全草。夏、秋采集,切碎,晒干。性味:《云南中草药》:"甘淡,平。"主治:清热解毒,散瘀消肿。治肺炎,扁桃体炎,腮腺炎,瘰疬,脓肿疮毒,骨折,创伤感染。①《云南中草药》:"清热解毒,消肿止痛。治骨折,淋巴结结核,腮腺炎,外伤出血。"②《云南中草药选》:"消炎拔毒,生肌,散瘀生新,杀虫。治急性化脓性扁桃体炎,肺炎,疮毒脓肿,伤口感染生蛆。"③《贵州药植目录》:"治劳伤,发表。"
款冬花:别名:冬花。来源:本品为菊科植物款冬TussilagofarfaraL.的干燥花蕾。12月或地冻前当花尚未出土时采挖,除去花梗及泥沙,阴干。性味:辛、微苦,温。归经:归肺经。主治:润肺下气,止咳化痰。用于新久咳嗽,喘咳痰多,劳嗽咳血。
竻慈姑:出处:《岭南采药录》。来源:为天南星科植物刺芋的根茎。夏、秋采收,洗净,晒干或切片晒干。性味:①《陆川本草》:"性凉,味淡。"②《南宁市药物志》:"甘,平。"主治:清热,利尿,解毒。治热病口渴,肺热咳嗽,小便黄赤,皮肤热毒。《陆川本草》:"消炎,解毒,利尿。治身热、口渴,头痛,小便黄赤,一般热性病。"《南宁市药物志》:"清热利尿,消肿散瘀。治肺热咳嗽,肠胃热毒,小便亦热,营养性浮肿。"
阿利藤:出处:《福建民间草药》。别名:念珠藤(《广州植物志》),瓜子藤、瓜子英、山红木、过山香、春根藤、过骨边(《福建民间草药》),瓜子金(《浙江中药资源名录》),七里香(《福建中草药》)。来源:为夹竹桃科植物链珠藤的全草及根。性味:苦辛,温,有小毒。①《福建民间草药》:"苦,平,有毒。"②《闽东本草)):"性温,味微苦辛,有小毒。"归经:《闽东本草》:"入肺、肝、脾三经。"主治:《福建民间草药》:"解热镇痛,消痈解毒。"《闽东本草》:"醒脾理气,舒筋通络.祛风活血。治胸膈胀闷,骨节酸痛,腹中冷痛泄泻,周身浮肿及妇人经闭。"
桂叶素馨:出处:《云南思茅中草药选》。别名:岭南茉莉(《中国树木分类学》),大黑骨头(《云南思茅中草药选》),鸭色盖(傣名)。来源:为木犀科植物桂叶素馨的全草。全年可采,晒干。性味:苦,寒。主治:清热解毒,消炎利尿,消肿散瘀。
降真香:出处:《证类本草》。别名:紫藤香(《卫济宝书》),降真(《真腊风土记》),降香(《纲目》)。来源:为豆科植物降香檀的根部心材。全年皆产,将根部挖出后,削去外皮,锯成长约50厘米的段,晒干。性味:辛,温。①《海药本草》:"温平,无毒。"归经:入肝、脾经。主治:理气,止血,行瘀,定痛。治吐血,咯血,金疮出血,跌打损伤,痈疽疮肿,风湿腰腿痛,心胃气痛。
假蒟果穗:出处:广州部队《常用中草药手册》。别名:假蒟子(广州部队《常用中草药手册》)。来源:为胡椒科植物假蒟的果穗。性味:广州部队《常用中草药手册》:"微辛,温。"主治:①广州部队《常用中草药手册》:"温中暖胃,驱风行气。治腹胀腹痛,肠炎腹泻,食欲不振,肾炎水肿,风湿痛。"②《广东中草药》:"化湿消肿,行气通窍,消滞化痰。治水肿,风湿性关节炎,疝气痛,风寒咳嗽。"
戟叶石苇:出处:《西藏常用中草药》。别名:渣贝筝瓦(藏名)。来源:为水龙骨科植物戟叶石苇的全草。孢子囊群成熟时采收。割取地上部分,刷去黄毛,切段,晒干。性味:性平,味苦甘。主治:利水通淋,清泄肺热。治肾炎水肿,泌尿系感染,尿道结石,肺热咳嗽,咯血,支气管哮喘,咽喉炎等症。
排骨灵:出处:《云南中草药选》。别名:广香藤(《植物名实图考》),满山香(《云南中草药选》)。来源:为番荔枝科植物多苞瓜馥木的根皮。全年可采。切段、晒干。性味:《云南中草药选》:"辛涩,温。"主治:①《植物名实图考》:"解毒,养血,清热。"②《云南中草药选》:"舒筋,活血,消炎,止血。治外伤出血,骨折,跌打损伤。"
蓬莪术:出处:侯宁极《药谱》。性味:苦辛,温。①《开宝本草》:"味苦辛;温,无毒。"②《医学启源》:"味苦,平。"归经:入肝、脾经。①《雷公炮制药性解》:"入肺、脾二经。"②《本草汇言》:"入足厥阴肝经。"③《本草再新》:"入心、肾二经。"主治:行气,破血,消积,止痛。治心腹胀痛,症瘕,积聚,宿食不消,妇女血瘀经闭,跌打损伤作痛。《会约医镜》:"治气滞膨胀,气肿,水肿。"
苤蓝叶:【出处】《滇南本草》。【来源】为十字花科植物球茎甘蓝的叶。【功能主治】治食积,痰积,恶疮。①《滇南本草》:"敷恶疮。"②《农政全书》:"叶及子:消食积,解面毒。"苤蓝叶素馨花:出处:《纲目》。别名:耶悉茗花(《南方草木状》),野悉蜜(《酉阳杂俎》),玉芙蓉(《花镜》),素馨针(《广东中药》)。来源:为木犀科植物素馨花的干燥花蕾。夏、秋采收,在清晨太阳未出时采摘花蕾,隔水蒸约20分钟,然后取出晒干。性味:《广东中药》Ⅱ:"性平,无毒。"《常用中草药手册》:"治肝炎、肝硬化的肝区痛。胸肋不舒,心胃气痛,下痢腹痛。"
所述药物组合物中各原料药材的重量份数比为:素馨花15-25重量份、红头小仙9-18重量份、雪灵芝15-35重量份、地皮消13-27重量份、降真香11-31重量份、兰石草14-26重量份、苤蓝叶15-35重量份、露水草9-18重量份、款冬花12-24重量份、绿绒蒿2-4重量份、桂叶素馨11-21重量份、蓬莪术14-36重量份、佛手露11-24重量份、梵天花10-30重量份、戟叶石苇12-22重量份、芥子15-35重量份、竻慈姑13-31重量份和紫花景天15-25重量份。
所述药物组合物中各原料药材的重量份数比为:素馨花22重量份、红头小仙14重量份、雪灵芝32重量份、地皮消24重量份、降真香30重量份、兰石草25重量份、苤蓝叶35重量份、露水草16重量份、款冬花22重量份、绿绒蒿3重量份、桂叶素馨20重量份、蓬莪术32重量份、佛手露20重量份、梵天花30重量份、戟叶石苇14重量份、芥子33重量份、竻慈姑27重量份和紫花景天21重量份。
所述药物组合物中各原料药材的重量份数为:素馨花15-25重量份、红头小仙9-18重量份、雪灵芝15-35重量份、地皮消13-27重量份、降真香11-31重量份、兰石草14-26重量份、苤蓝叶15-35重量份、露水草9-18重量份、款冬花12-24重量份、绿绒蒿2-4重量份、桂叶素馨11-21重量份、蓬莪术14-36重量份、佛手露11-24重量份、梵天花10-30重量份、戟叶石苇12-22重量份、芥子15-35重量份、竻慈姑13-31重量份、紫花景天15-25重量份、阿利藤3-5重量份、柴胡10-30重量份、假蒟果穗15-25重量份和排骨灵10-20重量份。
所述药物组合物中各原料药材的重量份数为:素馨花22重量份、红头小仙14重量份、雪灵芝32重量份、地皮消24重量份、降真香30重量份、兰石草25重量份、苤蓝叶35重量份、露水草16重量份、款冬花22重量份、绿绒蒿3重量份、桂叶素馨20重量份、蓬莪术32重量份、佛手露20重量份、梵天花30重量份、戟叶石苇14重量份、芥子33重量份、竻慈姑27重量份、紫花景天21重量份、阿利藤3重量份、柴胡12重量份、假蒟果穗23重量份和排骨灵15重量份。
所述药物组合物的剂型为粉针剂,其制备方法包括以下步骤:
第一步,将所述原料药材按比例混合,放入超微粉碎机中粉碎成0.1~10μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第二步,在第一步获得的混合粉料中加入相对于所述混合粉料的质量3~5倍的醇浓度为85%~95%的乙醇,搅拌溶解获得乙醇溶液,将乙醇溶液在5℃~10℃的条件下静置24~36小时,采用渗漉法以每分钟1~2ml的速度缓缓渗漉,收集渗漉液,浓缩并干燥,并在此放入超微粉碎机中粉碎40~60分钟,获得0.1~10μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第三步,取第二步获得的混合粉料10g~20g,加入丙二醇30g~50g,加200ml注射用水,搅拌使其溶解,进一步加注射用水至1000ml,再加入1g~1.5g针用活性炭,充分搅拌30~50分钟;脱炭过滤;用0.22~0.24μm微孔滤膜过滤;冷冻干燥得无菌粉末,分装灌封。
所述药物组合物的剂型为散剂,其制备方法包括以下步骤:
第一步,将地皮消、降真香、兰石草、苤蓝叶和露水草按所述比例混合,用相对于获得的混合物质量的3~5倍的醇浓度为85%~95%的乙醇溶解,加热回流2~4小时后提取,过滤,得第一过滤液;将滤渣再次用相对于获得的混合物质量的1~2倍的醇浓度85%~95%的乙醇溶解,加热回流1~2小时后提取,过滤,得第二过滤液;合并第一过滤液和第二过滤液,减压回收乙醇并浓缩至药液浓度为0.7~0.9g生药/mL,经体积为5L的大孔吸附树脂柱洗脱,先用5倍树脂柱体积的去离子水或蒸馏水洗脱,再用3倍树脂柱体积的醇浓度为90%~95%乙醇洗脱,收集乙醇洗脱液,减压浓缩除去乙醇,干燥并粉碎成粉末;
第二步,将梵天花、戟叶石苇、芥子、竻慈姑和紫花景天按所述比例混合,加相对于获得的混合物质量的2~4倍的醇浓度85%~95%的乙醇,加热回流提取1~2次,提取液合并,用管式离心机离心除杂,将除杂后的提取液于60℃~70℃的条件下减压浓缩至60℃时相对密度为1.20~1.23的膏体,将浓缩后的膏体用喷雾干燥器干燥成粉末;
第三步,将剩余原料药材按所述比例混合,加相对于获得的混合物质量的2~4倍的水溶解,加热煎煮2~4小时,过滤;将滤渣再次用相对于获得的混合物质量的1~2倍的水溶解,再次加热煎煮1~2小时,过滤;合并两次的过滤液,减压浓缩除去水分,干燥并粉碎成粉末;
第四步,将第一步、第二步和第三步获得的粉末混合,随后过筛成80~120目的细粉,将获得的细粉投入混合搅拌机中搅拌,即获得散剂。
以下采用实施例来详细说明本发明的实施方式,借此对本发明如何应用技术手段来解决技术问题,并达成技术效果的实现过程能充分理解并据以实施。
实施例1药物组合物1
本发明实施例提供了一种防治牛传染性胸膜肺炎的药物组合物,由以下重量份数的原料药材制成:素馨花22重量份、红头小仙14重量份、雪灵芝32重量份、地皮消24重量份、降真香30重量份、兰石草25重量份、苤蓝叶35重量份、露水草16重量份、款冬花22重量份、绿绒蒿3重量份、桂叶素馨20重量份、蓬莪术32重量份、佛手露20重量份、梵天花30重量份、戟叶石苇14重量份、芥子33重量份、竻慈姑27重量份和紫花景天21重量份。
第一步,将所述原料药材按比例混合,放入超微粉碎机中粉碎成3μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第二步,在第一步获得的混合粉料中加入相对于所述混合粉料的质量4倍的醇浓度为90%的乙醇,搅拌溶解获得乙醇溶液,将乙醇溶液在9℃的条件下静置30小时,采用渗漉法以每分钟2ml的速度缓缓渗漉,收集渗漉液,浓缩并干燥,并在此放入超微粉碎机中粉碎50分钟,获得4μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第三步,取第二步获得的混合粉料15g,加入丙二醇40g,加200ml注射用水,搅拌使其溶解,进一步加注射用水至1000ml,再加入1.5g针用活性炭,充分搅拌40分钟;脱炭过滤;用0.23μm微孔滤膜过滤;冷冻干燥得无菌粉末,分装灌封。
实施例2药物组合物2
本发明实施例提供了一种防治牛传染性胸膜肺炎的药物组合物,由以下重量份数的原料药材制成:素馨花22重量份、红头小仙14重量份、雪灵芝32重量份、地皮消24重量份、降真香30重量份、兰石草25重量份、苤蓝叶35重量份、露水草16重量份、款冬花22重量份、绿绒蒿3重量份、桂叶素馨20重量份、蓬莪术32重量份、佛手露20重量份、梵天花30重量份、戟叶石苇14重量份、芥子33重量份、竻慈姑27重量份、紫花景天21重量份、阿利藤3重量份、柴胡12重量份、假蒟果穗23重量份和排骨灵15重量份。
第一步,将地皮消、降真香、兰石草、苤蓝叶和露水草按所述比例混合,用相对于获得的混合物质量的4倍的醇浓度为90%的乙醇溶解,加热回流3小时后提取,过滤,得第一过滤液;将滤渣再次用相对于获得的混合物质量的2倍的醇浓度90%的乙醇溶解,加热回流2小时后提取,过滤,得第二过滤液;合并第一过滤液和第二过滤液,减压回收乙醇并浓缩至药液浓度为0.8g生药/mL,经体积为5L的大孔吸附树脂柱洗脱,先用5倍树脂柱体积的去离子水或蒸馏水洗脱,再用3倍树脂柱体积的醇浓度为90%乙醇洗脱,收集乙醇洗脱液,减压浓缩除去乙醇,干燥并粉碎成粉末;
第二步,将梵天花、戟叶石苇、芥子、竻慈姑和紫花景天按所述比例混合,加相对于获得的混合物质量的3倍的醇浓度90%的乙醇,加热回流提取2次,提取液合并,用管式离心机离心除杂,将除杂后的提取液于65℃的条件下减压浓缩至60℃时相对密度为1.22的膏体,将浓缩后的膏体用喷雾干燥器干燥成粉末;
第三步,将剩余原料药材按所述比例混合,加相对于获得的混合物质量的3倍的水溶解,加热煎煮3小时,过滤;将滤渣再次用相对于获得的混合物质量的1.5倍的水溶解,再次加热煎煮1.5小时,过滤;合并两次的过滤液,减压浓缩除去水分,干燥并粉碎成粉末;
第四步,将第一步、第二步和第三步获得的粉末混合,随后过筛成100目的细粉,将获得的细粉投入混合搅拌机中搅拌,即获得散剂。
药物组合物的毒性试验:
1、试验药物
选取素馨花22g、红头小仙14g、雪灵芝32g、地皮消24g、降真香30g、兰石草25g、苤蓝叶35g、露水草16g、款冬花22g、绿绒蒿30g、桂叶素馨20g、蓬莪术32g、佛手露20g、梵天花30g、戟叶石苇14g、芥子33g、竻慈姑27g和紫花景天21g混合,粉碎成粉末;将获得粉末加入1400g冷水中浸泡25小时,以文火煎煮,煎煮时间为1.5小时,将煎煮液过滤,获得第一滤液,收集滤渣;将过滤获得的滤渣再次加入1400g冷水中,以文火煎煮3次,每次煎煮1小时,过滤并合并过滤液,获得第二滤液;合并两次滤液,减压浓缩除去部分水,获得汤剂,汤剂的生药浓度为3g/ml。
2、试验方法:选用SD大鼠,给予不同浓度(18.0、6.0、2.0g生药/kg)的本发明的中药添加剂的汤剂,每天灌胃一次,连续90天,末次给药后24小时各组活杀1/2动物(雌雄各半),其余1/2动物继续观察2周后活杀。试验期间观察动物的外观、一般行为、摄食量、体重变化,给药后90天和停药2周进行血液学(RBC、HB、网织红细胞、PLT、CT、WBC及分类)和血液生化(AST、ALT、ALP、Glu、BUN、Crca、TP、T.BIL、ALB、CHOL)、尿液生化、脏器系数、病理组织学等指标检查。试验结果表明:本发明的中药添加剂在高、中、低剂量组动物一般状态良好,外观体征、行为活动、进食量和体重增长均无异常变化;三个剂量组及对照组血液学检查、血液生化学、尿液生化检查均在正常范围,组间无显著差异;各组主要脏器组织病理学检查未见明显异常。上述指标停药2周后也未见改变。本试验用药剂量分别为临床用药剂量的180、60、20倍,根据试验结果本发明的药物组合物在高、中、低三个剂量(18.0、6.0、2.0g生药/kg)连续90天给药对大鼠无明显影响,无明确的毒性靶器官和敏感指标,恢复期观察也未见延迟性毒性反应,提示本发明的药物组合物临床应用的剂量安全性较高。
临床试验
(1)材料准备
实验鸡及场地选取:
选择内蒙八拜牛养殖场的17个牛场为实验基地,随机选取300头平均年龄1.5岁的牛,作为治疗对比试验对象。另随机选取该17个鸡场健康300头平均年龄1.5岁的牛作为预防对比试验对象。
(2)菌株提取:
对内蒙八拜牛养殖场的17个养牛场的20只传染性胸膜肺炎死牛进行剖检,无菌采取病牛的胸腺、肺部、骨髓、脾脏等组织,将采集的病料用灭菌PBS研磨,终浓度1000μ/ml的双抗37℃下作用30min,反复冻融3-4次,离心,上清液加入血清的肉汤琼脂作用15min,期间不停振摇,70℃处理5min,离心,上清液经0.22μm滤膜过滤,置低温冰箱冻存,备用。
(3)预防对比实验:
从上述300头健康牛选取180头随机分成3组(实施例1组、实施例2组和对照组),其中,对实施例1组、实施例2组和对照组分别使用本发明实施例1的粉针剂、实施例2的散剂和传统药物进行预防;其中,粉针剂采用皮下注射,每次60mg/kg,每天两次,连续注射6天;散剂的使用方法是将散剂按照7g:500g的重量比例传统饲料中,连续饲喂6天;对照组:使用传统牛饲料饲喂牛,6天后,对对实施例1组、实施例2组和对照组进行人工感染用备用的培养物的5倍稀释液,腹腔注射0.3mL/只,观察记录各组鸡的发病率及死亡率,结果如表1所示。
表1预防效果对照表
组别 | 总数 | 人工感染数 | 发病率 | 死亡数 | 死亡率 | 保护率 |
实施例1组 | 60 | 60 | 0 | 0 | 0 | 100% |
实施例2组 | 60 | 60 | 0 | 0 | 0 | 100% |
对照组2 | 60 | 0 | 24% | 0 | 40% | 60% |
从表1的数据可知:本发明的药组物组合物对牛传染性胸膜肺炎有明显的预防效果。
(4)治疗对比试验:
用过滤的上清液腹腔注射的180头平均年龄1.5岁的病牛,随机分成3组(实施例治疗组、西药治疗组、空白对照组),出现临床症状后服用不同药,其中,实施例治疗组选用实施例1的药物组合物1,药量为每只每日0.5g,治疗5天;西药治疗组选用“九一四”溶于5%葡萄糖盐水,进行颈部注射,治疗5天;空白对照组不喂任何药物。观察记录各组牛的发病率、治愈率和死亡率,结果如表2所示。
表2治疗效果对照表
组别 | 发病数 | 发病率 | 死亡数 | 死亡率 | 治愈数 | 治愈率 |
实施例治疗组 | 60 | 100% | 3 | 5% | 57 | 95% |
西药治疗组 | 60 | 100% | 12 | 20% | 48 | 80% |
空白对照组 | 60 | 100% | 30 | 50% | - | - |
从表2的数据可知:本发明药物组合物对牛传染性胸膜炎治疗效果明显优于西药治疗组,降低死亡率,提高治愈率。
以上所述仅为本发明的较佳实施例,并不用以限制本发明,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.一种防治牛传染性胸膜肺炎的药物组合物,其特征在于,所述药物组合物包括以下原料药材:素馨花、红头小仙、雪灵芝、地皮消、降真香、兰石草、苤蓝叶、露水草、款冬花、绿绒蒿、桂叶素馨、蓬莪术、佛手露、梵天花、戟叶石苇、芥子、竻慈姑和紫花景天。
2.根据权利要求1所述的防治牛传染性胸膜肺炎的药物组合物,其特征在于,所述药物组合物中各原料药材的重量份数比为:素馨花15-25重量份、红头小仙9-18重量份、雪灵芝15-35重量份、地皮消13-27重量份、降真香11-31重量份、兰石草14-26重量份、苤蓝叶15-35重量份、露水草9-18重量份、款冬花12-24重量份、绿绒蒿2-4重量份、桂叶素馨11-21重量份、蓬莪术14-36重量份、佛手露11-24重量份、梵天花10-30重量份、戟叶石苇12-22重量份、芥子15-35重量份、竻慈姑13-31重量份和紫花景天15-25重量份。
3.根据权利要求1或2所述的防治牛传染性胸膜肺炎的药物组合物,其特征在于,所述药物组合物中各原料药材的重量份数比为:素馨花22重量份、红头小仙14重量份、雪灵芝32重量份、地皮消24重量份、降真香30重量份、兰石草25重量份、苤蓝叶35重量份、露水草16重量份、款冬花22重量份、绿绒蒿3重量份、桂叶素馨20重量份、蓬莪术32重量份、佛手露20重量份、梵天花30重量份、戟叶石苇14重量份、芥子33重量份、竻慈姑27重量份和紫花景天21重量份。
4.根据权利要求1-3任一项所述的防治牛传染性胸膜肺炎的药物组合物,其特征在于,所述药物组合物还包括:阿利藤、柴胡、假蒟果穗和排骨灵。
5.根据权利要求1-4任一项所述的防治牛传染性胸膜肺炎的药物组合物,其特征在于,所述药物组合物中各原料药材的重量份数为:素馨花15-25重量份、红头小仙9-18重量份、雪灵芝15-35重量份、地皮消13-27重量份、降真香11-31重量份、兰石草14-26重量份、苤蓝叶15-35重量份、露水草9-18重量份、款冬花12-24重量份、绿绒蒿2-4重量份、桂叶素馨11-21重量份、蓬莪术14-36重量份、佛手露11-24重量份、梵天花10-30重量份、戟叶石苇12-22重量份、芥子15-35重量份、竻慈姑13-31重量份、紫花景天15-25重量份、阿利藤3-5重量份、柴胡10-30重量份、假蒟果穗15-25重量份和排骨灵10-20重量份。
6.根据权利要求1-5任一项所述的防治牛传染性胸膜肺炎的药物组合物,其特征在于,所述药物组合物中各原料药材的重量份数为:素馨花22重量份、红头小仙14重量份、雪灵芝32重量份、地皮消24重量份、降真香30重量份、兰石草25重量份、苤蓝叶35重量份、露水草16重量份、款冬花22重量份、绿绒蒿3重量份、桂叶素馨20重量份、蓬莪术32重量份、佛手露20重量份、梵天花30重量份、戟叶石苇14重量份、芥子33重量份、竻慈姑27重量份、紫花景天21重量份、阿利藤3重量份、柴胡12重量份、假蒟果穗23重量份和排骨灵15重量份。
7.根据权利要求1-6任一项所述的防治牛传染性胸膜肺炎的药物组合物,其特征在于,所述药物组合物的剂型为粉针剂,其制备方法包括以下步骤:
第一步,将所述原料药材按比例混合,放入超微粉碎机中粉碎成0.1~10μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第二步,在第一步获得的混合粉料中加入相对于所述混合粉料的质量3~5倍的醇浓度为85%~95%的乙醇,搅拌溶解获得乙醇溶液,将乙醇溶液在5℃~10℃的条件下静置24~36小时,采用渗漉法以每分钟1~2ml的速度缓缓渗漉,收集渗漉液,浓缩并干燥,并在此放入超微粉碎机中粉碎40~60分钟,获得0.1~10μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第三步,取第二步获得的混合粉料10g~20g,加入丙二醇30g~50g,加200ml注射用水,搅拌使其溶解,进一步加注射用水至1000ml,再加入1g~1.5g针用活性炭,充分搅拌30~50分钟;脱炭过滤;用0.22~0.24μm微孔滤膜过滤;冷冻干燥得无菌粉末,分装灌封。
8.根据权利要求1-6任一项所述的防治牛传染性胸膜肺炎的药物组合物,其特征在于,所述药物组合物的剂型为散剂,其制备方法包括以下步骤:
第一步,将地皮消、降真香、兰石草、苤蓝叶和露水草按所述比例混合,用相对于获得的混合物质量的3~5倍的醇浓度为85%~95%的乙醇溶解,加热回流2~4小时后提取,过滤,得第一过滤液;将滤渣再次用相对于获得的混合物质量的1~2倍的醇浓度85%~95%的乙醇溶解,加热回流1~2小时后提取,过滤,得第二过滤液;合并第一过滤液和第二过滤液,减压回收乙醇并浓缩至药液浓度为0.7~0.9g生药/mL,经体积为5L的大孔吸附树脂柱洗脱,先用5倍树脂柱体积的去离子水或蒸馏水洗脱,再用3倍树脂柱体积的醇浓度为90%~95%乙醇洗脱,收集乙醇洗脱液,减压浓缩除去乙醇,干燥并粉碎成粉末;
第二步,将梵天花、戟叶石苇、芥子、竻慈姑和紫花景天按所述比例混合,加相对于获得的混合物质量的2~4倍的醇浓度85%~95%的乙醇,加热回流提取1~2次,提取液合并,用管式离心机离心除杂,将除杂后的提取液于60℃~70℃的条件下减压浓缩至60℃时相对密度为1.20~1.23的膏体,将浓缩后的膏体用喷雾干燥器干燥成粉末;
第三步,将剩余原料药材按所述比例混合,加相对于获得的混合物质量的2~4倍的水溶解,加热煎煮2~4小时,过滤;将滤渣再次用相对于获得的混合物质量的1~2倍的水溶解,再次加热煎煮1~2小时,过滤;合并两次的过滤液,减压浓缩除去水分,干燥并粉碎成粉末;
第四步,将第一步、第二步和第三步获得的粉末混合,随后过筛成80~120目的细粉,将获得的细粉投入混合搅拌机中搅拌,即获得散剂。
9.一种如权利要求1-6任一项所述的防治牛传染性胸膜肺炎的药物组合物的制备方法,其特征在于,所述药物组合物的剂型为粉针剂,其制备方法包括以下步骤:
第一步,将所述原料药材按比例混合,放入超微粉碎机中粉碎成0.1~10μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第二步,在第一步获得的混合粉料中加入相对于所述混合粉料的质量3~5倍的醇浓度为85%~95%的乙醇,搅拌溶解获得乙醇溶液,将乙醇溶液在5℃~10℃的条件下静置24~36小时,采用渗漉法以每分钟1~2ml的速度缓缓渗漉,收集渗漉液,浓缩并干燥,并在此放入超微粉碎机中粉碎40~60分钟,获得0.1~10μm体积平均粒径的微米级颗粒和粒径小于0.1μm体积平均粒径的纳米级颗粒组成的混合粉料,所述混合粉料的得粉率至少为95%;
第三步,取第二步获得的混合粉料10g~20g,加入丙二醇30g~50g,加200ml注射用水,搅拌使其溶解,进一步加注射用水至1000ml,再加入1g~1.5g针用活性炭,充分搅拌30~50分钟;脱炭过滤;用0.22~0.24μm微孔滤膜过滤;冷冻干燥得无菌粉末,分装灌封。
10.一种如权利要求1-6任一项所述的防治牛传染性胸膜肺炎的药物组合物的制备方法,其特征在于,所述药物组合物的剂型为散剂,其制备方法包括以下步骤:
第一步,将地皮消、降真香、兰石草、苤蓝叶和露水草按所述比例混合,用相对于获得的混合物质量的3~5倍的醇浓度为85%~95%的乙醇溶解,加热回流2~4小时后提取,过滤,得第一过滤液;将滤渣再次用相对于获得的混合物质量的1~2倍的醇浓度85%~95%的乙醇溶解,加热回流1~2小时后提取,过滤,得第二过滤液;合并第一过滤液和第二过滤液,减压回收乙醇并浓缩至药液浓度为0.7~0.9g生药/mL,经体积为5L的大孔吸附树脂柱洗脱,先用5倍树脂柱体积的去离子水或蒸馏水洗脱,再用3倍树脂柱体积的醇浓度为90%~95%乙醇洗脱,收集乙醇洗脱液,减压浓缩除去乙醇,干燥并粉碎成粉末;
第二步,将梵天花、戟叶石苇、芥子、竻慈姑和紫花景天按所述比例混合,加相对于获得的混合物质量的2~4倍的醇浓度85%~95%的乙醇,加热回流提取1~2次,提取液合并,用管式离心机离心除杂,将除杂后的提取液于60℃~70℃的条件下减压浓缩至60℃时相对密度为1.20~1.23的膏体,将浓缩后的膏体用喷雾干燥器干燥成粉末;
第三步,将剩余原料药材按所述比例混合,加相对于获得的混合物质量的2~4倍的水溶解,加热煎煮2~4小时,过滤;将滤渣再次用相对于获得的混合物质量的1~2倍的水溶解,再次加热煎煮1~2小时,过滤;合并两次的过滤液,减压浓缩除去水分,干燥并粉碎成粉末;
第四步,将第一步、第二步和第三步获得的粉末混合,随后过筛成80~120目的细粉,将获得的细粉投入混合搅拌机中搅拌,即获得散剂。
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