CN116983392A - 一种含有硫酸黏菌素的可溶性颗粒及其制备方法 - Google Patents
一种含有硫酸黏菌素的可溶性颗粒及其制备方法 Download PDFInfo
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- CN116983392A CN116983392A CN202310866967.7A CN202310866967A CN116983392A CN 116983392 A CN116983392 A CN 116983392A CN 202310866967 A CN202310866967 A CN 202310866967A CN 116983392 A CN116983392 A CN 116983392A
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- colistin sulfate
- water
- lysozyme
- colistin
- soluble
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Abstract
本发明属于药物制剂技术领域,涉及一种含有硫酸黏菌素的可溶性颗粒及其制备方法。该制剂的配方包括以下成分(按重量百分比计):硫酸黏菌素10%,莽草酸3‑5%,溶菌酶3‑5%,聚氧乙烯(40)氢化蓖麻油0.5‑1%,AEO‑9 1‑2%,水溶性淀粉3%,聚维酮K30 0.5%,异麦芽酮糖醇73.5‑79%。本发明所制备的硫酸黏菌素可溶性颗粒比市面上的硫酸黏菌素可溶性粉效果更佳,对仔猪腹泻具有高效的防治效果。本发明的颗粒剂具有高溶水性,加入水中能快速分散溶解,特别是在冬季较低的温度,饮水给药使用方便且质量稳定、易于储运,不易结块;本发明的辅料易得,采用沸腾制粒机生产,制备工艺简单,操作简单,适合工业化生产和市场推广。
Description
技术领域
本发明涉及药物制剂技术领域,具体涉及一种含硫酸黏菌素的可溶性颗粒及其制备方法。
背景技术
仔猪腹泻已经成为影响仔猪成活率的一个重要因素,在我国,30kg以下的仔猪腹泻发病率约为50%。死亡率可达15%以上,每年仔猪腹泻造成的经济损失达上亿元。严重影响我国养猪业的经济效益。
引起仔猪腹泻的病原很多,其中包括传染性胃肠炎病毒、轮状病毒、球虫和大肠杆菌,但由大肠杆菌引起的腹泻是主要的。据Bergland(1980)报道,新生仔猪腹泻由大肠杆菌引起的占45%以上,高于其它病原。随着大型集约化畜禽养殖业的发展,病原性大肠杆菌对畜牧业所造成的损失已日趋明显。仔猪腹泻引起猪只生长缓慢,饲料报酬降低,生产性能下降,延长出栏时间,甚至引起猪只出现死亡,给养猪业造成巨大的经济损失。
硫酸黏菌素为一种碱性阳离子表面活性剂,具有杀菌作用,其能与细菌细胞膜内的磷脂相互作用而渗入膜内,破坏膜结构,进而使膜通透性发生变化,导致细菌死亡。硫酸黏菌素对需氧菌以及如大肠杆菌、肺炎杆菌、绿脓杆菌、嗜血杆菌、沙门氏菌和志贺氏菌等革兰氏阴性菌有较强的抗菌作用。对黏菌素敏感的细菌很少产生耐药性。
硫酸黏菌素临床运用广泛,通常为饮水给药,采用浓配的方式溶解后,再通过加压泵至供水系统稀释到临床用量。一般而言,溶解度高、溶解速度快的饮水药物更易受养殖用户青睐。水溶性差将直接导致产品在使用过程中生物利用度大打折扣。硫酸黏菌素由于自身的特性,加入水中药物会聚合漂浮在水上,溶解过程中气泡较多,需要较长时间搅拌才能溶解;拌料使用时也易结团,导致混合不匀,而且由于硫酸黏菌素的引湿性,产品在高温高湿条件下也易结块,这些给养殖户或养殖企业带来了诸多不便,增加了能耗。为解决以上困扰,产品制剂工艺方面,将其加工为颗粒,由于原料熔点较低、粘度大,普通的制粒易结块,流化床造粒易粘塔或板结,产品收率低,损失大。因此,在这些问题上,广大制剂工作者仍然面对着巨大的挑战。
莽草酸又称3,4,5-三羟基-1-环己烯-1-甲酸,分子式:C7H10O5,主要存在于木兰科植物八角茴香的干燥果实中,也存在于其他高等植物、微生物中,如巴山冷杉、马尾松等。性状为白色精细粉末,易溶于水。莽草酸具有抗炎、镇痛作用,还可作为抗病毒和抗癌药物中间体,在体内莽草酸可转化为多种对病毒、细菌和癌细胞有抑杀作用的物质。作为抗病毒性药物,它主要用于防治禽流行性感冒、传染性支气管炎、传染性喉气管炎、新城疫、传染性法氏囊等病毒性疾病。
溶菌酶,即N-乙酰胞壁质酶,抗菌机理为作用于细菌细胞壁N-乙酰胞壁酸(NAM)与N-乙酰葡萄糖胺之间的β-1,4-糖甘键,使细胞壁不溶性多糖分解成可溶性糖肽,细菌内容物逸出而使细菌溶解。它可与各种诱发炎症的酸性物质结合,使其失活,并能增强其它药物的疗效,改善组织基质的粘多糖代谢,从而达到消炎、修复组织的目的;此外,它可以阻止流感和腺病毒繁殖,同带负电荷的病毒蛋白直接作用,与DNA、RNA、脱辅基蛋白形成复盐,使病毒失活。同时,它还可以增强免疫,其作为机体非特异性免疫因子之一,参与机体多种免疫反应,在机体正常防御功能和非特异免疫中,具有保持机体生理平衡的重要作用。
目前对于仔猪腹泻主要采用抗生素进行预防和治疗,但由于长期使用或滥用抗生素,耐药性问题、安全问题、残留问题越来越成为人们关注的焦点。另外,利巴韦林、金刚烷胺等各种抗病毒药物已被农业部明令严禁使用。综上所述,当前急需一种使用方便、高效、稳定的药物预防和治疗仔猪腹泻。
发明内容
针对现有技术中存在的问题,本发明提供了一种含有硫酸黏菌素的可溶性颗粒及其制备方法,不仅改善了硫酸黏菌素的溶水性能,而且解决了存放中易结块的问题。该颗粒剂,活性成分由硫酸黏菌素、莽草酸、溶菌酶组成,具有抗菌、抗病毒、抗炎和增强免疫力的功效,各原料协同作用,对仔猪腹泻具有高效防治效果,并且几乎不呈现毒副作用,且可提高饲料转化率,促进仔猪生长。
为解决上述技术问题,本发明的技术方案是:
一种含有硫酸黏菌素的可溶性颗粒,按重量百分比,其配方组分为硫酸黏菌素10%、莽草酸3-5%、溶菌酶3-5%、聚氧乙烯(40)氢化蓖麻油0.5-1%、AEO-91-2%、水溶性淀粉3%、聚维酮K30 0.5%、异麦芽酮糖醇73.5-79%,上述八种组分重量百分比之和为100%。其中,水溶性淀粉在常温(25℃)状态下,在水中的溶解度大于60g/100ml;溶菌酶的酶活力不低于5000u/mg。
一种含有硫酸黏菌素的颗粒剂的制备方法,包括以下步骤:
(1)将异麦芽酮糖醇、溶菌酶、莽草酸、硫酸黏菌素分别粉碎至80-100目,过80目筛,上述各成分按配方分别称取备用;
(2)将配方量的水溶性淀粉、聚维酮K30加入到适量的纯化水中,搅拌溶解,然后加入聚氧乙烯(40)氢化蓖麻油、AEO-9,搅拌均匀,得到含15%(W/W)水溶性淀粉的粘合剂溶液A;
(3)将粉碎过筛后的异麦芽酮糖醇、溶菌酶、莽草酸、硫酸黏菌素吸入沸腾制粒机,混合10-15分钟,然后将混合物料加热至40-50℃;
(4)向沸腾制粒机中喷入步骤(2)制备的粘合剂溶液A,造粒,沸腾制粒机工艺参数为进风温度80-90℃、出风温度40-45℃、喷射速度100-150r/min,雾化程度:压缩空气耗量30-45m3/h;
(5)粘合剂溶液A喷完后,缓慢升温烘干颗粒,但不得超过60℃,烘20-30分钟,以水分干燥失重率不过3%为标准,停止烘干,取出包装即得所述含有硫酸黏菌素的颗粒剂。
由于采用了上述技术方案,本发明的有益效果是:
1、本发明制备的一种含硫酸黏菌素的颗粒剂,以聚氧乙烯(40)氢化蓖麻油、莽草酸为助溶剂,AEO-9为分散剂、消泡剂,异麦芽酮糖醇为载体,水溶性淀粉、聚维酮K30为粘合剂,制备的颗粒溶水时快速分散溶解,泡沫少,不结团,不粘壁,颗粒具有非常好的水溶性且溶解度可长期稳定在20000ppm以上,使用方便,完全满足市场需求,高于市售硫酸黏菌素可溶性粉。
2、本发明中水溶性淀粉、聚维酮K30具备成膜性,能隔绝水分,可很好地防止产品在储运中结块。
3、本发明的可溶颗粒主要由硫酸黏菌素、莽草酸和溶菌酶三种有效成分组成,三者间相互协同,不仅抗细菌和抗病毒作用强,而且具有消炎、增强机体免疫力作用,对仔猪腹泻具有高效防治效果。
4、本发明制备的一种含硫酸黏菌素的颗粒剂,采用沸腾制粒机制备颗粒,不板结,不粘锅,收率可达90%以上。工艺可行,可操作性强,质量稳定,颗粒剂的流动性好,与可溶性粉相比在饲料混合过程中更易混匀,工业化生产、市场前景广阔。
附图说明
图1为实施例1、2、3的颗粒剂在粘菌素浓度为20000ppm时,在15min时的溶解情况;
图2为对比例1、4、5的制剂在粘菌素浓度为20000ppm时,在20min时的溶解情况;
图3为实施例3的颗粒剂在粘菌素浓度为20000ppm时,在5min时的溶解情况;
图4为对比例5的可溶性粉在粘菌素浓度为20000ppm时,在5min时的溶解情况。
具体实施方式
为使本申请的发明目的、发明内容呈现得更加清楚,下面申请人结合实施例对本发明作进一步描述,但本发明的保护范围并不限于这些实施例。本领域技术人员应理解,对本发明的技术特征所作的等同替换,或相应的改进,仍属于本发明的保护范围之内。
下述各实施例和对比例中所使用的实验方法如无特殊说明,均为常规方法;所使用的材料、试剂等,如无特殊说明,均可从商业途径得到。
下述各实施例和对比例中所使用的溶菌酶为购自上海中华药业有限公司的鸡蛋清溶菌酶,酶活力为5000u/mg。
实施例1:
一种含硫酸黏菌素的颗粒剂,其原辅料包括:硫酸黏菌素100g、莽草酸30g、溶菌酶30g、聚氧乙烯(40)氢化蓖麻油5g、AEO-9 10g、水溶性淀粉30g、聚维酮K30 5g、异麦芽酮糖醇790g;
本实施例的含硫酸黏菌素的颗粒剂的制备方法,包括以下工艺步骤:
(1)将异麦芽酮糖醇、溶菌酶、莽草酸、硫酸黏菌素分别粉碎至80-100目,过80目筛,上述各成分按配方分别称取,备用;
(2)将30g水溶性淀粉、5g聚维酮K30加入到150g纯化水中,搅拌溶解,再加入5g聚氧乙烯(40)氢化蓖麻油、10g AEO-9,搅拌均匀后,得到粘合剂溶液A。
(3)将粉碎过筛后的硫酸黏菌素100g、莽草酸30g、溶菌酶30g、异麦芽酮糖醇790g吸入沸腾制粒机,混合10分钟,然后将混合物料加热至40-42℃;
(4)向沸腾制粒机中喷入步骤(2)制备的粘合剂溶液A,造粒,沸腾制粒机工艺参数为进风温度80℃、出风温度40℃、喷射速度100r/min,雾化程度:压缩空气耗量30m3/h;
(5)粘合剂溶液A喷完后,缓慢升温烘干颗粒,不超过60℃,烘20分钟,以水分干燥失重率不过3%为标准,停止烘干,取出包装即可。
经测定:颗粒剂中硫酸黏菌素的含量为9.83%(以粘菌素计),颗粒剂的收率为93.2%,其中,收率=步骤(5)所得颗粒剂的质量(g)/1000*100%,下同,不再赘述。
实施例2:
一种含硫酸黏菌素的颗粒剂,其原辅料包括:硫酸黏菌素100g、莽草酸40g、溶菌酶40g、聚氧乙烯(40)氢化蓖麻油5g、AEO-9 15g、水溶性淀粉30g、聚维酮K30 5g、异麦芽酮糖醇765g;
本实施例的含硫酸黏菌素的颗粒剂的制备方法,包括以下工艺步骤:
(1)将异麦芽酮糖醇、溶菌酶、莽草酸、硫酸黏菌素分别粉碎至80-100目,过80目筛,上述各成分按配方分别称取,备用;
(2)将30g水溶性淀粉、5g聚维酮K30加入到145g纯化水中,搅拌溶解,再加入5g聚氧乙烯(40)氢化蓖麻油、15g AEO-9,搅拌均匀后,得到粘合剂溶液A。
(3)将粉碎过筛后的硫酸黏菌素100g、莽草酸40g、溶菌酶40g、异麦芽酮糖醇765g吸入沸腾制粒机,混合12分钟,然后将混合物料加热至44-46℃;
(4)向沸腾制粒机中喷入步骤(2)制备的粘合剂溶液A,造粒,沸腾制粒机工艺参数为进风温度85℃、出风温度45℃、喷射速度130r/min,雾化程度:压缩空气耗量35m3/h;
(5)粘合剂溶液A喷完后,缓慢升温烘干颗粒,不超过60℃,烘25min,以水分干燥失重率不过3%为标准,停止烘干,取出包装即可。
经测定:颗粒剂中硫酸黏菌素的含量为9.78%(以粘菌素计),颗粒剂的收率为91.45%。
实施例3:
一种含硫酸黏菌素的可溶性颗粒,其原辅料包括:硫酸黏菌素100g、莽草酸50g、溶菌酶50g、聚氧乙烯(40)氢化蓖麻油10g、AEO-9 20g、水溶性淀粉30g、聚维酮K30 5g、异麦芽酮糖醇735g;
本实施例的含硫酸黏菌素的可溶性颗粒的制备方法,包括以下工艺步骤:
(1)将异麦芽酮糖醇、溶菌酶、莽草酸、硫酸黏菌素分别粉碎至80-100目,过80目筛,上述各成分按配方分别称取,备用;
(2)将30g水溶性淀粉、5g聚维酮K30加入到135g纯化水中,搅拌溶解,再加入10g聚氧乙烯(40)氢化蓖麻油、20g AEO-9,搅拌均匀后,得到粘合剂溶液A。
(3)将粉碎过筛后的硫酸黏菌素100g、莽草酸50g、溶菌酶50g、异麦芽酮糖醇735g吸入沸腾制粒机,混合15分钟,然后将混合物料加热至48-50℃;
(4)向沸腾制粒机中喷入步骤(2)制备的粘合剂溶液A,造粒,沸腾制粒机工艺参数为进风温度90℃、出风温度45℃、喷射速度150r/min,雾化程度:压缩空气耗量40m3/h;
(5)粘合剂溶液A喷完后,缓慢升温烘干颗粒,不超过60℃,烘30min,以水分干燥失重率不过3%为标准,停止烘干,取出包装即可。
经测定:颗粒剂中硫酸黏菌素的含量为9.82%(以粘菌素计),颗粒剂的收率为90.95%。
对比例1
一种含硫酸黏菌素的可溶性颗粒,其原辅料包括:硫酸黏菌素100g、溶菌酶30g、水溶性淀粉30g、聚维酮K30 5g、异麦芽酮糖醇835g;
本对比例的含硫酸黏菌素的颗粒剂的制备方法,包括以下工艺步骤:
(1)将异麦芽酮糖醇、溶菌酶、硫酸黏菌素分别粉碎至80-100目,过80目筛,上述各成分按配方分别称取,备用;
(2)将水溶性淀粉30g、聚维酮K30 5g加入到165g纯化水中,搅拌溶解,得到粘合剂溶液A。
(3)将粉碎过筛后的硫酸黏菌素100g、溶菌酶30g、异麦芽酮糖醇835g吸入沸腾制粒机,混合10分钟,然后将混合物料加热至40-42℃;
(4)向沸腾制粒机中喷入步骤(2)制备的粘合剂溶液A,造粒,沸腾制粒机工艺参数为进风温度80℃、出风温度40℃、喷射速度100r/min,雾化程度:压缩空气耗量30m3/h;
(5)粘合剂溶液A喷完后,缓慢升温烘干颗粒,不超过60℃,烘20分钟,以水分干燥失重率不过3%为标准,停止烘干,取出包装即可。
经测定:颗粒剂中硫酸黏菌素的含量为9.74%(以粘菌素计),颗粒剂的收率为93.57%。
对比例2
按实施例3的方法制备,不同之处在于本颗粒中不含硫酸黏菌素,其原辅料包括:莽草酸50g、溶菌酶50g、聚氧乙烯(40)氢化蓖麻油10g、AEO-9 20g、水溶性淀粉30g、聚维酮K30 5g、异麦芽酮糖醇835g;
经测定:颗粒剂的收率为96.17%。
对比例3
按实施例3的方法制备,不同之处在于本颗粒中不含异麦芽酮糖醇及水溶性淀粉,替代成载体葡萄糖,其原辅料包括:硫酸黏菌素100g、莽草酸50g、溶菌酶50g、聚氧乙烯(40)氢化蓖麻油10g、AEO-9 20g、聚维酮K30 15g、葡萄糖755g;
经测定:颗粒剂中硫酸黏菌素的含量为8.18%(以粘菌素计),颗粒剂的收率为68.27%。
分析:该对比例在试验过程中出现黏结、粘锅现象,导致颗粒剂中硫酸黏菌素的含量偏低,收率不足。分析原因主要为更换载体及粘合剂导致,说明载体和粘合剂选择不当,将影响实现产业化生产。
对比例4
称取硫酸黏菌素10g,加葡萄糖90g,混合均匀即可。
对比例5
市售10%硫酸黏菌素可溶性粉,广东科润生物制药有限公司生产,批号为20220310。
实施例4溶解性试验
按照《中国兽药典》2020年版中可溶性粉剂的溶解性标准:取实施例1、2、3及对比例1、4、5共6个样品各适量(约0.4g),置纳氏比色管中,分别加水制成100ml的溶液(以黏菌素计,浓度为猪临床使用高剂量浓度的2倍),在23-27℃上下翻转10次,供试品应全部溶解,静置30分钟,不得有浑浊或沉淀生成。
室温下(10-30℃),称取实施例1、2、3及对比例1、4、5共6个样品,各20g,分别加水制成100ml的溶液,搅拌30分钟,搅拌过程中检查对比溶液的溶解情况,结果见下表1及附图。
表1:各试验样品在粘菌素浓度为20000ppm时的溶解情况
试验结论:样品按药典方法检验溶解性时,均合格。按猪临床使用时高剂量浓度的100倍溶解样品时,实施例组和对比例组存在明显差异。实施例组均在15分钟内溶解澄清,无泡沫,见附图1;随着莽草酸的增加,溶解性更好。实施例3在5分钟内溶解完全,表面有少量泡沫,8分钟内泡沫完全消失。以黏菌素计,药物浓度达到20000ppm。对比例在20min内均不能溶解完全且有泡沫,见附图2。说明以聚氧乙烯(40)氢化蓖麻油、莽草酸为助溶剂,AEO-9为分散剂、消泡剂,制备的颗粒能快速分散溶解,泡沫少,且溶水性能明显提高。另外,对比例1与4、5相比,颗粒剂优于可溶性粉,其未溶物和泡沫均少于可溶性粉。另外颗粒样品与粉末样的溶解过程也存在差异,颗粒样溶解过程不黏玻璃棒,以实施例3为例,搅拌情况见附图3,粉末样以对比例5为例,在搅拌过程中黏玻璃棒,见附图4。
本发明的硫酸黏菌素可溶颗粒在临床推荐用量的100倍浓度范围内可迅速、完全溶解澄清,能有效地满足用户饮水给药时,先浓配后稀释的用法需求。
实施例5稳定性试验
取实施例1-3的颗粒及对比例1、4、5的产品分别进行高温稳定性试验和加速试验,考察本发明颗粒剂的稳定性,确认是否有变色、结块、潮解、变性等不稳定现象出现,并按《中国兽药典》(2020年版)中“可溶性粉剂”通则中“溶解性”的标准检验制剂的水溶性是否合格。
5.1、高温稳定性试验
取样品敞口置于60℃下保存10d,然后恢复至室温观察。结果表明,实施例1-3及对比例1的颗粒剂,外观性状未发生明显变化,无变色、结块、潮解、变性等情况发生,水溶性检验合格,说明实施例1-3的颗粒及对比例1的颗粒在高温下稳定性良好。对比例4、5在高温条件下外观变黄,有结团现象。说明制备成颗粒是有利于其高温稳定性的。
5.2、常温留样观察试验
取样品敞口置于常温(25±2℃)下,分别在制备后第0d、30d、60d、120d和180d进行观察。结果表明,实施例1-3及对比例1的颗粒,外观性状未发生明显变化,无变色、结块、潮解、变性等情况发生,水溶性检验合格,说明样品在室温稳定性良好。对比例4、5的样品分别在第30d、120d出现潮解,结团,颜色轻微变黄现象。
5.3、加速试验
样品采用铝箔袋包装,置于温度40℃、相对湿度75%的加速箱中贮存90d,每隔30d取样观察。结果表明,实施例1-3及对比例1的颗粒热贮后,外观性状未发生明显变化,无变色、结块、潮解、变性等情况发生,水溶性检验合格,说明热贮稳定性良好。对比例4、5的样品均在90d出现潮解,结团,颜色变黄现象。
实施例6安全性试验
选取42日龄健康仔猪30头,取用本发明实施例3所制得的颗粒,每1L水中添加200mg剂量(以黏菌素计),5倍灌服,即每头猪每天的灌服量为1000ppm(以黏菌素计),灌服10天。用药期间,健康猪没有任何不良或异常表现,采食和饮水均正常,体重增加与空白对照组(未给药健康仔猪)无明显差异。说明本发明制得的颗粒安全无毒副作用,对仔猪生长无不良影响。
实施例7临床疗效试验
对仔猪大肠杆菌病的疗效观察
病例:某猪场有1000头42日龄左右的仔猪,有173头仔猪出现腹泻,排出灰白色粥状或糊状粪便,且有腥臭味,有时粪便中混有气泡。仔猪出现食欲减退、精神沉郁、行走不稳、消瘦的症状,喜卧垫料或挤压成堆。根据流行病学、临床症状、剖检变化及致病性大肠杆菌(EPEC)核酸检测试剂盒确定仔猪群发生了仔猪白痢,由致病性大肠杆菌引起。
方法:在相同饲养条件下随机将病猪分成空白对照组、阳性对照组、试验组;空白对照组,每日正常饲喂饲料,饲喂5d;阳性对照组,每日正常饲喂饲料,每1L水中添加50mg剂量(以黏菌素计)的对比例4、5的样品,进行口服服用,连用5d,对比例2的添加量同对比例4、5;试验组,每日正常饲喂饲料,每1L水中添加50mg剂量(以黏菌素计)的实施例1-3的颗粒剂,进行口服服用,连用5d。
疗效判定标准
治愈:基本无呕吐、腹泻、脱水等症状,肠道消化正常,精神状态良好。
显效:呕吐、腹泻次数减少,脱水症状减轻,精神状态好转。
无效:临床症状加重,甚至死亡。
有效:为治愈与显效的总和。
治疗结果
用药5天后,对患病仔猪进行临床检查,结果见表1。
表1不同药物对仔猪白痢的疗效考察结果
注:有效率(%)=有效数*100%/病例数,治愈率(%)=治愈数*100%/病例数。
结果表明,连续用药5d后,对比例组和实施例组的有效率与治愈率,都高于仔猪自愈空白组的有效率与治愈率;未添加硫酸黏菌素的对比例2组的有效率与治愈率仅优于空白对照组,低于对比例4-5组,远低于实施例组,说明单独使用莽草酸和溶菌酶不能起到很好的防治效果;但添加了莽草酸和溶菌酶的实施例组的有效率与治愈率又高于对比例4-5组,说明莽草酸和溶菌酶的添加对实施例组起到了增效的目的。
Claims (6)
1.一种含有硫酸黏菌素的可溶性颗粒,其特征在于,以重量百分比计,其配方包括如下比例的组分:
硫酸黏菌素 10%
莽草酸 3-5%
溶菌酶 3-5%
聚氧乙烯(40)氢化蓖麻油 0.5-1%
AEO-9 1-2%
水溶性淀粉 3%
聚维酮K30 0.5%
异麦芽酮糖醇 73.5-79%。
2.根据权利要求1所述的含有硫酸黏菌素的可溶性颗粒,其特征在于:所述水溶性淀粉在常温25℃状态下,在水中的溶解度大于60g/100ml。
3.根据权利要求1所述的含有硫酸黏菌素的可溶性颗粒,其特征在于:所述溶菌酶的酶活力不低于5000u/mg。
4.一种权利要求1-3中任一所述含有硫酸黏菌素的可溶性颗粒的制备方法,其特征在于,包括以下步骤:
(1)将异麦芽酮糖醇、溶菌酶、莽草酸、硫酸黏菌素分别粉碎过筛后,按配方分别称取备用;
(2)将配方量的水溶性淀粉、聚维酮K30加入到纯化水中,搅拌溶解,然后加入聚氧乙烯(40)氢化蓖麻油、AEO-9 ,搅拌均匀,得到粘合剂溶液A;
(3)将粉碎过筛后的异麦芽酮糖醇、溶菌酶、莽草酸、硫酸黏菌素吸入沸腾制粒机,混合10-15分钟,然后将混合物料加热至40-50℃;
(4)向沸腾制粒机中喷入步骤(2)制备的粘合剂溶液A,造粒,沸腾制粒机工艺参数为进风温度80-90℃、出风温度40-45℃、喷射速度100-150r/min,雾化程度:压缩空气耗量30-45m3/h;
(5)粘合剂溶液A喷完后,缓慢升温烘干颗粒,但不得超过60℃,烘20-30分钟,以水分干燥失重率不过3%为标准,停止烘干,取出包装即可。
5.根据权利要求4所述的制备方法,其特征在于,步骤(1)中将异麦芽酮糖醇、溶菌酶、莽草酸、硫酸黏菌素分别粉碎至80-100目,过80目筛。
6.根据权利要求4所述的制备方法,其特征在于,步骤(2)的粘合剂溶液A中,水溶性淀粉的质量百分比为15%。
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