CN115192683A - 治疗/预防霉菌毒素中毒的中药组合物及其制备方法、用途 - Google Patents
治疗/预防霉菌毒素中毒的中药组合物及其制备方法、用途 Download PDFInfo
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Abstract
本发明涉及中兽药技术领域,具体涉及一种用于治疗/预防霉菌毒素中毒的中药组合物及其制备方法和用途。该中药组合物由以下重量份数的原料制成:金银花30~36份、柴胡24~31份、黄芪15~21份、茵陈蒿8~14份、郁金8~14份。本发明的中药组合物在治愈疾病的同时,可提升机体免疫功能,并改善生长状态;还能够有效治疗霉菌毒素中毒引发的各种症状,同时可提升肝脏解毒能力,促进肾脏排泄毒素,防止继发感染,增加机体的抗病能力。
Description
技术领域
本发明涉及中兽药技术领域,具体而言,涉及一种用于治疗/预防霉菌毒素中毒的中药组合物及其制备方法和用途。
背景技术
霉菌是丝状真菌的统称,在自然界分布极广,种类极多,目前有记载的约有3500~10000种,造成谷物和饲料污染破坏的常见霉菌近200种。大多数霉菌在自身滋生过程中能分泌活性很强的酶,使谷物中的淀粉、蛋白质和脂肪等有机物变成可溶状态而被摄取,分解供其生长繁殖所需,因此造成粮食、饲料的霉变,大大降低其营养价值。据相关研究统计,每年全世界的谷物约有25%受到霉菌及霉菌毒素的污染,对于人类健康、公共卫生安全及动物的生长及生产性能均造成极大的危害。霉菌毒素是指霉菌在其所污染的谷物或饲料中生长繁殖过程中所产生的一系列有毒的次级代谢产物。目前已知、常见的对人和动物危害相对严重的霉菌毒素有:黄曲霉毒素B1(AFB1)、赭曲霉毒素A(OTA)、T-2毒素、玉米赤霉烯酮(ZEA)、烟曲霉毒素毒素(FUM)、以及呕吐毒素(DON)等。霉菌毒素严重抑制动物的免疫系统功能,可通过与机体的DNA、RNA结合并抑制其合成进而影响合成蛋白质;可通过作用于机体淋巴组织引起器官萎缩及发育不良,导致淋巴细胞生成减少;可影响肝脏及巨噬细胞的功能。不同的霉菌毒素毒性作用有一定差异性,黄曲霉毒素靶器官为肝脏、赭曲霉毒素靶器官为肾脏、玉米赤霉烯酮具有类雌激素样作用以及烟曲霉毒素对呼吸系统的破坏作用等。
研究发现一共有13种真菌可以代谢产生赭曲霉毒素,其中有7种曲霉属真菌和6种青霉菌,赭曲霉毒素主要由赭曲霉菌种产生。赭曲霉毒素有多种,通常指赭曲霉毒素A、B和C,其中毒性最强最主要的是赭曲霉毒素A(OTA),且耐热性极强。赭曲霉毒素具有较强的肾毒性,可导致肾小管变性和机能损伤,造成肾小管间质纤维结构化和肾小管上皮细胞坏死,肾小球渗透以及肾小球体积扩张引发肾功能受损;在黏液囊中引起淋巴结萎缩和减少骨髓淋巴细胞团的数量,皮质和髓质的淋巴结出现空泡变性;在胸腺中会减少胸腺实质中的淋巴细胞团数量引起免疫抑制。OTA通过诱导氧化应激、抑制蛋白质合成、诱导细胞凋亡、干扰细胞信号转导、诱发线粒体损伤等因素发挥其毒理作用,具体为:损害线粒体的呼吸作用而导致ATP的耗竭;影响蛋白质合成和DNA及RNA的合成,能通过竞争抑制苯丙氨酸-TRNAL连接酶,从而降低蛋白质合成;增加细胞中的脂质过氧化物。
OTA具有显著的肾毒性、肝毒性、发育毒性、神经毒性、免疫毒性,同时具有致癌致畸致突变作用。猪、牛、禽、马等动物均对OTA敏感。畜禽长时间采食含有霉菌毒素的霉变饲料后,可直接导致动物生长受阻、生产性能下降、饲料转化率下降、繁殖性能降低,对疾病的敏感性增强,组织器官受损等临床症状,严重者出死亡。可导致家禽产蛋率、受精率下降,畸形蛋、破壳蛋比例增加等症状。
当前,尚无有效治疗霉菌毒素的药物。针对饲料中霉菌毒素脱毒的方法主要有物理法、化学法、酶解法及吸附法等。但是现有的方法存在着破坏了饲料的营养成分及适口性、脱毒效率不高、且成本较高等问题。使用吸附剂处理则存在选择性吸附和吸附营养物质的缺点、微生物降解脱毒法存在着需要经过筛选有吸附作用的菌体,工艺复杂,生产成本高的问题。霉菌毒素种类繁多,且毒素间分子结构和理化性质也差异较大,现有脱毒方法吸附营养素,稳定性一般,存在不良反应。脱霉剂只能吸附部分霉菌毒素,不能彻底清除,更不能修复霉菌毒素带来的机体损伤。
现在针对霉菌毒素的治疗方法主要是使用制霉菌素、克霉唑等进行治疗,使用维生素进行加速代谢、缓解毒性,投服硫酸镁、人工盐导泻排毒等方法,但这些方法均对于已经吸收入血的霉菌毒素给机体造成的损伤起不到修复治疗作用。在减抗限抗的背景下,抗生素的应用受到极大限制,而且抗生素只能单纯杀灭霉菌,对霉菌毒素中毒无从解决。现有技术中已有采用中药组合物来防止霉菌毒素中毒,但是,到目前为止,现有的中药组合物存在着成分复杂、处方过大、功效欠佳,不能有效防治霉菌毒素中毒引起的病理损伤的缺陷,因此,研发一种疗效确切、无副作用、无耐药性、非抗生素类、无药物残留、安全、高效、环保且能够有效预防/治疗霉菌毒素中毒的中药组合物至关重要。
发明内容
为解决现有技术的不足,本发明提供了一种用于治疗/预防霉菌毒素中毒的中药组合物及其制备方法和应用。不仅可以弥补现有治疗药物的药物残留多、毒副作用大等不足之处,同时兼有成本低廉、适宜畜禽生理结构、适宜工厂规模化生产的特点,同时具有优秀的治疗效果。
本发明的中药组合物通过各组分的协调配合作用能够有效治疗霉菌毒素中毒及其导致的各种临床症状,可促进发病畜禽的愈后,效果显著,安全性高,可有效增强机体免疫力,恢复并提升生产性能,适宜在多个领域进行临床推广应用。
本发明第一个目的是提供一种中药组合物,其由以下重量份数的原料制成:
金银花30~36份、柴胡24~31份、黄芪15~21份、茵陈蒿8~14份、郁金8~14份。
优选地,所述的中药组合物由以下重量份数的原料制成:金银花31~35份、柴胡25~29份、黄芪16~20份、茵陈蒿9~13份、郁金9~13份。
优选地,所述的中药组合物由以下重量份数的原料制成:金银花33份、柴胡27份、黄芪18份、茵陈蒿11份、郁金11份。
本发明第二个目的是提供所述中药组合物在制备治疗/预防霉菌毒素中毒的药物中的用途。
本发明第三个目的是提供所述中药组合物的制备方法,包括以下步骤:按重量份数称取金银花、柴胡、黄芪、茵陈蒿及郁金,混合后进行超声波提取,提取液依次进行浓缩、静置、离心,调节离心所得上清液的pH至6.5~7.0后过滤。
优选地,所述超声波提取前将药材粉碎至粒径为350μm~600μm,再加入相当于药材混合物4~8倍量的提取溶剂浸泡0.5h~1.5h;
所述超声波提取是以相当于药材混合物总重6~9倍量的水和/或醇为提取溶剂,在功率30kHz~40kHz、温度72℃~88℃下提取1~3次,每次0.5h~1.0h。
优选地,所述浓缩是采用真空负压浓缩,设置真空度为-0.08Mpa~-0.18Mpa,温度为70℃~85℃,将提取液浓缩至原料混合物质量的1.1~1.4倍;
所述静置是在4℃~6℃下静置10h~20h;
所述离心的转速为9000rpm~11000rpm;
所述过滤是采用孔径为0.22μm~0.45μm的微孔滤膜进行。
本发明第四个目的是提供一种用于治疗/预防霉菌毒素中毒的药物,以质量百分比计,包括如上所述的中药组合物1%~99%和辅料1%~99%。
本发明第五个目的是提供一种复合饲料,以质量百分比计,包括如上所述的中药组合物10%~90%和饲料10%~90%。
本发明第六个目的是提供一种饲料添加剂,以质量百分比计,包括如上所述的中药组合物10%~90%和辅料10%~90%。
与现有技术相比,本发明的有益效果为:
(1)本发明在中医、中兽医理论的基础上进行组方,选择以保肝解毒、疏肝解郁、清热利湿、健脾温肾为治则,组方中药材组方的选择及用量均经过系统的药理学与药效学研究,科学合理,对于治疗/预防畜禽霉菌毒素中毒具有显著的功效,与现有技术仅针对霉菌毒素进行物理吸附或针对中毒症状进行治疗不同,通过对证进行治疗,祛除病因,达到彻底治愈疾病。
(2)本发明的中药组合物为纯中药提取制剂,不含化药及抗生素,无毒,无药物残留,绿色环保。
(3)本发明所应用的原料均为市场上常见的药材,价廉易得,成本低,适合临床推广使用。
(4)本发明的中药组合物在治愈疾病的同时,可提升机体免疫功能,并改善生长状态;还能够有效治疗霉菌毒素中毒引发的各种症状,同时可提升肝脏解毒能力,促进肾脏排泄毒素,防止继发感染,增加机体的抗病能力。
(5)本发明的中药组合物制备方法中采用药材提前粉碎、过筛、浸泡等过程,有效去除杂质,增加药材的比表面积,显著的增加药效物质溶出度,同时采用超声提取技术进行提取,显著的增加了药物提取液的生物活性,并且工艺简便,节能、高效、省时、生产周期短,极大的降低了生产成本。
(6)本发明的中药组合物用于制备治疗/预防霉菌毒素中毒的药物、饲料或者饲料添加剂,治疗霉菌毒素中毒的效果优异。
具体实施方式
下面将结合实施例对本发明的实施方案进行详细描述,但是本领域技术人员将会理解,下列实施例仅用于说明本发明,而不应视为限制本发明的范围。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市购获得的常规产品。
根据本发明的一个方面,本发明涉及一种用于治疗/预防霉菌毒素中毒的中药组合物,主要由以下重量份数的原料制成:
金银花30~36份、柴胡24~31份、黄芪15~21份、茵陈蒿8~14份和郁金8~14份。
金银花,性寒、味甘,归肺、胃、心经。具有清热解毒之功效,主治外感风热或温病初起、暑热、外疡内痈、热毒泻痢等。主要成分为绿原酸、异绿原酸、黄酮类(木犀草素等)、忍冬苷、肌醇、皂苷及挥发油、鞣质等。具有抗病原体、广谱抗菌作用、抗炎、抑制炎性渗出及炎性增生、解热、保肝、增加胃肠蠕动、促进胃液及胆汁分泌、降血脂等作用。
柴胡,性微寒、味苦辛,归肝、胆经。具有和解退热、疏肝解郁、升举阳气之功效,主治伤寒邪在少阳证、肝郁气滞证、气虚下陷诸症。柴胡善条达肝气而疏肝解郁,用于肝气郁结;善升清阳之气而举陷,用于气虚下陷诸证。主要成分为柴胡皂苷、柴胡醇、挥发油、芸香苷及生物碱等。具有解热镇痛、镇静、抗惊厥、抗炎、保肝利胆、增强免疫功能、抗病原体、抗氧化等药理作用。
黄芪,性微温、味甘,归脾、肺经。具有补气升阳、益卫固表、托疮生肌、利水退肿之功效,主治脾气虚弱证、气不摄血证、中气下陷证、气血双亏证、气虚发热证、体虚多汗证、气虚水肿证等。主要成分为苷类、多糖、黄酮、氨基酸、微量元素等,包含黄芪皂苷甲,黄芪皂苷乙,胡萝卜甘,β-谷甾醇,黄芪皂苷I、II、IV,大豆皂苷,多糖I、II、III等。具有增强机体免疫功能、提高对霉菌毒素及内毒素的免疫作用、降低毒素对免疫系统的损伤、抗衰老、抗疲劳、抗缺氧、抗寒、强心、扩张血管、降压、促进蛋白质合成、调节血糖、保肝、护胃、保肾、利尿、抗菌、抗病毒、抗炎、镇静、镇痛等药理作用。
茵陈蒿,性微寒、味苦,归脾、胃、肝、胆经。具有清热利湿退黄之功效,主治黄疸、胆结石症、温湿病、湿疮、疥癣、风疹等。茵陈蒿清热利湿为治黄疸之要药,湿热之阳黄、寒湿之阴黄、湿热郁蒸、肝胆湿热蕴结均可使用,亦可用于湿温证湿热并重者。茵陈味淡利水,乃治脾胃二家湿热之专药。主要成分为6,7-二甲氧基香豆素,绿原酸、咖啡酸、挥发油(含α-蒎烯、β-蒎烯、茵陈二炔酮、茵陈二烯酮、茵陈烯炔、茵陈炔内酯、丁香酚、异丁香酚、茵陈素A、茵陈素B等)。具有利胆、保肝、降脂、抗菌、利尿、解热、驱杀蛔虫、减轻毒素对肝细胞损伤等药理作用。
郁金,性寒、味辛苦,归心、肝、胆经。具有活血止痛、行气解郁、清热凉血、清新开窍、利胆退黄之功效,主治胁痛、吐血、衄血、湿热黄疸等。郁金功能活血祛瘀而止痛,行气解郁而疏泄肝郁,为血分之气药。胁为肝之分野,肝郁疏泄失常,可致肝经受病,气滞胁痛,甚则血行不畅。湿热蕴结于肝胆,可致黄疸。郁金入胆经能利胆退黄,用治湿热黄疸,常与茵陈同用。主要成分为蒎烯、倍半萜烯、倍半萜烯醇、姜黄素等,具有降血脂、镇静、保肝、保护心肌、抗氧化等药理作用。
《普济方》卷二百五十二诸毒门中记述:“朽木生蕈,腐土生菌,二者皆阴湿之地气,蒸郁所生也。既非冲和所产,其必有毒。若误食之,令人吐利不已,心腹切痛,甚者身黑而死。生于树者为蕈,生于地者为菌,并是湿气蒸郁变化所生。有死,甚急速也;其不死者,尤能令人烦闷吐利,时久始醒也”。将霉菌辩证为阴湿之物,霉菌毒素更为阴中之阴,是为阴毒。霉菌毒素本性为阴,极易损伤机体五脏阳气。脾、肝、肾尤甚。脾主运化水湿,脾肾亏虚,水液代谢障碍导致湿气内停,湿气内停过久,容易引起湿郁化热,导致湿热内生。肝主藏血,主疏泄。肝脏具有解毒功能,霉菌毒素摄入至体内后,首先经过血液循环至肝脏,经肝药酶的分解代谢下转化为其他物质,经肾排泄出体外。在此代谢过程中,肝阳受损,肝失疏泄,解毒功能下降,毒素在体内蓄积。肾藏精,主生殖发育,主命门火,肾阳受损,正气受损,肾阳主一身之阳气,受损则不足以暖胞宫,导致免疫、消化、繁殖等功能严重受到影响。脾为后天之本,气血生化之源,脾阳不足则气血生化不足,脾阳虚亦可致中气下陷。因此根据中兽医学理论,霉菌毒素中毒可辩证为湿热下注肝胆。湿热郁结于肝胆,致使肝气不舒,胆汁分泌失常,脾胃运化功能减弱,脾气虚弱运化失健,气为血帅,气虚不能摄血,气虚无力运化,水湿停滞,则致浮肿尿少等症。
因此,本发明根据中医、中兽药理论进行辩证后,确定采取保肝解毒、疏肝解郁、清热利湿、健脾温肾为治则。方中:金银花为君药,清热解毒,具有保肝解毒、抗病原体、广谱抗菌等作用,可针对毒素进行解毒,标本兼治。柴胡为臣药,疏肝解郁,具有和解退热、保肝利胆、升举阳气之功效,善条达肝气而疏肝解郁,善升清阳之气而举陷,用于气虚下陷诸证。黄芪为臣药,入脾经为补益脾气之良药,既善于补气,又长于升阳,可健脾止泻。具有补气升阳、益卫固表、利水退肿之功效,主治脾气虚弱证、气不摄血证、中气下陷证、气血双亏证、气虚发热证、体虚多汗证、气虚水肿证等。茵陈蒿为佐药,具有清热利湿退黄之功效,为清热利湿为治黄疸之要药,湿热之阳黄、寒湿之阴黄、湿热郁蒸、肝胆湿热蕴结均可使用,亦可用于湿温证湿热并重者。郁金为佐药,功能活血祛瘀而止痛,行气解郁而疏泄肝郁,为血分之气药。胁为肝之分野,肝郁疏泄失常,可致肝经受病,气滞胁痛,甚则血行不畅。湿热蕴结于肝胆,可致黄疸。郁金入胆经能利胆退黄,用治湿热黄疸,常与茵陈同用。
本发明提供的用于治疗/预防霉菌毒素中毒的中药组合物或药物可进一步按照药学上或兽药学上常规的方法制备成口服液、颗粒剂、超微粉、片剂或丸剂。
当本发明提供的中药组合物制备成口服液时,以质量百分比计,包括所述中药组合物10%~90%和口服液辅料10%~90%;其中,口服液辅料包括抗氧化剂、pH调节剂、防腐剂和水。抗氧化剂选自亚硫酸钠、焦亚硫酸钠、硫代硫酸钠、EDTA-Na2中的一种或几种;pH调节剂选自盐酸、磷酸及磷酸盐类、柠檬酸及柠檬酸盐、乳酸、NaOH中的一种或几种;防腐剂选自苯甲酸、苯甲酸钠、对羟基苯甲酸酯类、山梨酸、山梨酸钾中的一种或几种,使用量为常规用量。
当本发明提供的中药组合物制备成饲料添加剂时,以质量百分比计,包括所述的中药组合物10%~90%和辅料10%~90%。其中,辅料包括稀释剂和防腐剂。辅料主要是指防腐剂:山梨酸钾、对羟基苯甲酸酯类以及用于溶解这些物质的乙醇。用量均为常规量,例如,山梨酸钾0.4%~0.6%(w/v)、尼泊金甲酯0.15%~0.25%(w/v)和尼泊金乙酯0.15%~0.25%(w/v);进一步优选为山梨酸钾0.5%(w/v)、尼泊金甲酯0.2%(w/v)和尼泊金乙酯0.2%(w/v)。
下面将结合具体的实施例和对比实施例对本发明作进一步地解释说明。
实施例1
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花33份、柴胡27份、黄芪18份、茵陈蒿11份、郁金11份。
所述中药组合物的制备方法,包括以下步骤:
将上述5味药材分别去杂,称重,粉碎制成粒径为550μm的粗粉,合并后加入5倍重量的纯化水,浸泡1h;将浸泡过后的药材及浸泡液加纯化水至药材重量的8倍,进行超声波提取,超声波提取的频率为35kHz,温度为79℃,提取3次,每次40min;合并3次的药材提取液,在80℃,-0.13Mpa真空度条件下,对药液进行浓缩,药液浓缩至原药材量的1.2倍后,将药液滤出,将药材提取液于4~6℃冷库中静置16h;取出冷库中静置16h的药材提取液,以10000rpm进行在线高速离心,离心后再次滤过药液;将离心液的pH值范围调节至7.0后,使用0.22μm微孔滤膜进行滤过,收集滤过液,加入辅料进行配制,配制后进行灌装,灭菌,即得成品。
实施例2
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花36份、柴胡24份、黄芪15份、茵陈蒿8份、郁金8份。
所述中药组合物的制备方法,包括以下步骤:
将上述5味药材分别去杂,称重,粉碎制成粒径为550μm的粗粉,合并后加入5倍重量的纯化水,浸泡1h;将浸泡过后的药材及浸泡液加纯化水至药材重量的8倍,进行超声波提取,超声波提取的频率为35kHz,温度为79℃,提取3次,每次40min;合并3次的药材提取液,在80℃,-0.13Mpa真空度条件下,对药液进行浓缩,药液浓缩至原药材量的1.2倍后,将药液滤出,将药材提取液于4~6℃冷库中静置16h;取出冷库中静置16h的药材提取液,以10000rpm进行在线高速离心,离心后再次滤过药液;将离心液的pH值范围调节至7.0后,使用0.22μm微孔滤膜进行滤过,收集滤过液,加入辅料进行配制,配制后进行灌装,灭菌,即得成品。
实施例3
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花30份、柴胡31份、黄芪15份、茵陈蒿8份、郁金8份。
制备方法同实施例2。
实施例4
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花35份、柴胡24份、黄芪15份、茵陈蒿8份、郁金10份。
制备方法同实施例2。
实施例5
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花34份、柴胡28份、黄芪19份、茵陈蒿12份、郁金10份。
制备方法同实施例2。
实施例6
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花34份、柴胡28份、黄芪21份、茵陈蒿14份、郁金14份。
制备方法同实施例2。
实施例7
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花31份、柴胡25份、黄芪16份、茵陈蒿9份、郁金9份。
制备方法同实施例2。
实施例8
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花31份、柴胡29份、黄芪20份、茵陈蒿13份、郁金13份。
制备方法同实施例2。
实施例9
一种治疗/预防霉菌毒素中毒的中药组合物,与实施例2的区别在于制备方法不同,具体为:
将上述5味药材分别去杂,称重,粉碎制成粒径为350μm的粗粉,合并后加入4倍重量的纯化水,浸泡0.5h;将浸泡过后的药材及浸泡液加纯化水至药材重量的6倍,进行超声波提取,超声波提取的频率为30kHz,温度为72℃,提取30min;在70℃,-0.08Mpa真空度条件下,对药液进行浓缩,药液浓缩至原药材量的1.1倍后,将药液滤出,将药材提取液于4~6℃冷库中静置10h;取出冷库中静置10h的药材提取液,以9000rpm进行在线高速离心,离心后再次滤过药液;将离心液的pH值范围调节至6.5后,使用0.22μm微孔滤膜进行滤过,收集滤过液,加入辅料进行配制,配制后进行灌装,灭菌,即得成品。
实施例10
一种治疗/预防霉菌毒素中毒的中药组合物,与实施例2的区别在于制备方法不同,具体为:
将上述5味药材分别去杂,称重,粉碎制成粒径为600μm的粗粉,合并后加入8倍重量的纯化水,浸泡1.5h;将浸泡过后的药材及浸泡液加纯化水至药材重量的9倍,进行超声波提取,超声波提取的频率为40kHz,温度为88℃,提取3次,每次1h;在85℃,-0.18Mpa真空度条件下,对药液进行浓缩,药液浓缩至原药材量的1.4倍后,将药液滤出,将药材提取液于4~6℃冷库中静置20h;取出冷库中静置20h的药材提取液,以11000rpm进行在线高速离心,离心后再次滤过药液;将离心液的pH值范围调节至7.0后,使用0.45μm微孔滤膜进行滤过,收集滤过液,加入辅料进行配制,配制后进行灌装,灭菌,即得成品。
对比实施例1
根据2006年中国农业出版社出版的《中兽医学》中针对发霉饲料中毒的处方及使用方法,取独活100g,桑寄生160g,秦艽60g,防风60g,细辛18g,牛膝50g,川芎60g,芍药60g,干地黄50g,当归100g,党参140g,杜仲60g,甘草45g,苍术80g,防己60g,车前子100g,薏苡仁100g,莱菔子250g(500只鸡1次用量),水煎2次,混合,侯温灌服。
对比实施例2
根据2006年中国农业出版社出版的《中兽医学》中针对发霉饲料中毒的处方及使用方法,取茵陈蒿、栀子、大黄各20g,水煎取汁,加入葡萄糖30~60g,维生素C 0.1~0.5g,混匀后供100只鸡饮水服用或猪1次灌服。
对比实施例3
白头翁口服液(药典方),取白头翁300g、黄连150g、秦皮300g、黄柏225g,以上4味,加水煎煮3次,合并煎液,滤过,滤液浓缩至相对密度为1.20~1.25,加入乙醇,使含醇量达到75%,静置12h,滤取上清液,残渣加75%乙醇适量,静置12h,滤过,合并乙醇液,回收乙醇,调节pH值至5.0,冷藏72h,滤过,滤液调节pH值至5.0,加水至975ml,灌装,灭菌,即得。用量为猪30~45ml,禽2~3ml。
对比实施例4
郁金散(药典方),由郁金30g,诃子15g,黄芩30g,大黄60g,黄连30g,黄柏30g,栀子30g,白芍15g,8味药材制成,经粉碎,过筛,混匀,即得。用量为每1kg饲料,猪45~60g。
对比实施例5
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花40份、柴胡20份、黄芪25份、茵陈蒿15份、郁金15份。
制备方法同实施例2。
对比实施例6
一种治疗/预防霉菌毒素中毒的中药组合物,由金银花、黄芪、茵陈蒿和郁金制成,按其重量份计算:金银花36份、黄芪15份、茵陈蒿8份、郁金8份。
制备方法同实施例2。
对比实施例7
一种治疗/预防霉菌毒素中毒的中药组合物,由蒲公英、黄芪、茵陈蒿和郁金制成,按其重量份计算:蒲公英36份、黄芪15份、茵陈蒿8份、郁金8份。
制备方法同实施例2。
对比实施例8
一种治疗/预防霉菌毒素中毒的中药组合物,由秦皮、柴胡、黄芪、茵陈蒿和郁金制成,按其重量份计算:秦皮36份、柴胡24份、黄芪15份、茵陈蒿8份、郁金8份。
制备方法同实施例2。
临床实验1:
肉鸡霉菌毒素中毒临床治疗试验
2021年7月,山西省运城市稷山县某规模化养禽场,因阴雨潮湿天气导致饲料霉变严重,其中一栋舍的6000余只25日龄肉鸡出现霉菌毒素中毒现象,发病家禽出现呼吸困难、采食量下降、饲料转化率降低、腹泻情况严重,剖检死亡鸡只可发现肾脏严重病变。饲料经过检测霉菌毒素超标,其中OTA毒素超标严重。根据临床症状、剖检情况及实验室诊断,确诊为霉菌毒素中毒。选取3150只发病鸡,随机将发病鸡群分为将试验鸡随机分为模型组、脱霉剂(市售脱霉剂)组、制霉菌素组、实施例1~10组、对比实施例1~8组,每组150只试验鸡。另取150只同日龄的健康鸡作为正常组,具体分组及给药情况见表1,7天后对比治疗效果。
表1实验分组及给药情况
试验结果如表2所示。
表2临床试验结果
注:字母不同表示差异极显著(P<0.01);“-”表示肾脏无损伤或损伤程度极轻微;“+”表示肾脏损伤明显;“++”表示肾脏损伤程度较深。“+++”表示肾脏损伤严重。
从表2中试验结果可以得知,实施例各组相较于各对比实施例组、脱霉剂组及制霉菌素组,可明显降低因霉菌毒素中毒导致的死淘,并提高治愈率、出栏重。其中,实施例1与其他实施例及对比实施例组、脱霉剂组及制霉菌素组相比较,可显著降低因霉菌毒素中毒导致的死淘,与正常组无显著性差异。实施例1组的治愈率显著高于其他各治疗组,其效果最佳。实施例1组的出栏重显著高于其他各治疗组,与正常组无显著性差异,显著恢复并提升了生产性能、降低了料肉比、增加了日增重,显示其可有效治疗霉菌毒素中毒,同时节约了大量的治疗费用,效果最佳。
临床实验2
蛋鸡霉菌毒素中毒临床试验
2021年8月,山西省运城市永济市某蛋鸡场,因阴雨潮湿天气导致饲料霉变,其中一栋舍的8000余只29周龄蛋鸡出现霉菌毒素中毒现象,鸡群出现死亡情况,采食量下降、产蛋率下降、饲料转化率降低、腹泻情况严重,剖检死亡鸡只可发现肾脏严重病变。饲料经过检测确定霉菌毒素超标,其中OTA毒素超标严重。根据临床症状、剖检情况及实验室诊断,确诊为霉菌毒素中毒。选取800只发病鸡,随机将发病鸡群分为将试验鸡随机分为空白对照组(不给药)、脱霉剂组、实施例1组、对比例2组,每组200只试验鸡;另选取其他栋舍健康蛋鸡200只作为正常组。具体分组及给药情况见表3,第1组使用本发明实施例1所制备的口服液进行饮水给药(以0.2%(v/v)剂量使用);第2组为对比实施例2组,使用对比实施例2处方进行饮水给药(以0.25%(v/v)剂量饮水使用),第3组为空白对照组,不使用任何药物;第4组为正常组;第五组为脱霉剂组,拌料使用(以5g/kg剂量拌料使用)。7天后对比治疗效果。
表3各组临床试验结果
组别 | 产蛋率(%) | 破蛋率(%) | 日耗料量(g) | 料蛋比 |
实施例1组 | 79.2 | 0.75 | 108.28 | 2.04 |
对比实施例2组 | 65.9 | 0.94 | 91.54 | 2.27 |
空白对照组 | 52.6 | 1.18 | 87.95 | 2.45 |
正常组 | 81.1 | 0.72 | 109.81 | 1.97 |
脱霉剂组 | 69.8 | 0.91 | 92.53 | 2.29 |
如表3中试验结果所示,实施例1组可显著霉菌毒素中毒禽的产蛋率,降低霉菌毒素造成的危害,提升生产性能,提升日耗量量,并显著降低料蛋比。
最后应说明的是:以上各实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述各实施例对本发明进行了详细的说明,但本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分或者全部技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
Claims (10)
1.一种用于治疗/预防霉菌毒素中毒的中药组合物,其特征在于,所述中药组合物由以下重量份数的原料药制成:
金银花30~36份、柴胡24~31份、黄芪15~21份、茵陈蒿8~14份、郁金8~14份。
2.根据权利要求1所述的治疗/预防霉菌毒素中毒的中药组合物,其特征在于,所述中药组合物由以下重量份数的原料药制成:
金银花31~35份、柴胡25~29份、黄芪16~20份、茵陈蒿9~13份、郁金9~13份。
3.根据权利要求1所述的治疗/预防霉菌毒素中毒的中药组合物,其特征在于,所述中药组合物由以下重量份数的原料药制成:
金银花33份、柴胡27份、黄芪18份、茵陈蒿11份、郁金11份。
4.权利要求1~3任一项所述的中药组合物在制备治疗/预防霉菌毒素中毒的药物中的用途。
5.权利要求1~3任一项所述的中药组合物的制备方法,其特征在于,包括以下步骤:按重量份数称取金银花、柴胡、黄芪、茵陈蒿及郁金,混合后进行超声波提取,提取液依次进行浓缩、静置、离心,调节离心所得上清液的pH至6.5~7.0后过滤,收集滤液。
6.根据权利要求5所述的制备方法,其特征在于,
所述超声波提取前将药材粉碎至粒径为350μm~600μm,再加入相当于药材混合物4~8倍量的提取溶剂浸泡0.5h~1.5h;
所述超声波提取是以相当于药材混合物总重6~9倍量的水和/或醇为提取溶剂,在功率30kHz~40kHz、温度72℃~88℃下提取1~3次,每次0.5h~1.0h。
7.根据权利要求6所述的制备方法,其特征在于,
所述浓缩是采用真空负压浓缩,设置真空度为-0.08Mpa~-0.18Mpa,温度为70℃~85℃,将提取液浓缩至原料混合物质量的1.1~1.4倍;
所述静置是在4℃~6℃下静置10h~20h;
所述离心的转速为9000rpm~11000rpm;
所述过滤是采用孔径为0.22μm~0.45μm的微孔滤膜进行。
8.一种用于治疗/预防霉菌毒素中毒的药物,其特征在于,以质量百分比计,包括权利要求1~3任一项所述的中药组合物1%~99%和辅料1%~99%。
9.一种复合饲料,其特征在于,以质量百分比计,包括权利要求1~3任一项所述的中药组合物10%~90%和饲料10%~90%。
10.一种饲料添加剂,其特征在于,以质量百分比计,包括权利要求1~3任一项所述的中药组合物10%~90%和辅料10%~90%。
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