CN111567678A - 无抗畜类肠道保健剂及其制备方法 - Google Patents
无抗畜类肠道保健剂及其制备方法 Download PDFInfo
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- CN111567678A CN111567678A CN202010392300.4A CN202010392300A CN111567678A CN 111567678 A CN111567678 A CN 111567678A CN 202010392300 A CN202010392300 A CN 202010392300A CN 111567678 A CN111567678 A CN 111567678A
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Abstract
本发明的目的是提供一种无抗畜类肠道保健剂的制备方法,采用靶向载药、控释包衣、肠溶包衣和混合等技术对微生态制剂、抗菌肽制剂、黏膜促进制剂和中兽药制剂等4中原料进行联用处理,制备得到一种无抗畜类肠道保健剂,在保证上述原料的保健功能得以充分发挥的基础上,利用原料间功能的相互促进和叠加,并根据原料对机体的保健机制进行释放时序的控制,使该无抗畜类肠道保健剂的整体保健效果得以进一步提升。
Description
技术领域
本发明涉及家畜肠道疾病防护技术领域,尤其是涉及一种无抗畜类肠道保健剂及其制备方法。
背景技术
畜类肠道疾病是规模养殖场常发疾病之一,其中,肠道腹泻严重影响畜类存活率,从而造成较大的经济损失。相关研究表明,肠道在消化吸收营养物质过程中发挥着重要的作用,是机体重要的免疫屏障。处于肠道受损或发育不全状态的家畜,其被动免疫力不足,更易受有害菌攻击而产生肠道疾病,进而导致个体对营养物质吸收利用率下降、生长速率减缓,从而形成恶性循环,严重威胁个体存活。
目前,规模养殖场仍依赖于抗菌药物对腹泻个体进行治疗并对群体进行日常防疫。由于对抗菌药物的过分依赖和使用,在畜类群体中产生了残留、耐药、环境威胁、甚至“抗生素相关性腹泻”等问题。而伴随着科技的发展和生活水平的提高,人们对动物福利和食品安全有了更高的要求,动物保健和“无抗”养殖已成为行业趋势。
发明内容
本发明的目的是提供一种无抗畜类肠道保健剂的制备方法,采用靶向载药、控释包衣、肠溶包衣和混合等技术对微生态制剂、抗菌肽制剂、黏膜促进制剂和中兽药制剂等4种原料进行联用处理,制备得到一种无抗畜类肠道保健剂,在保证上述原料的保健功能得以充分发挥的基础上,利用原料间功能的相互促进和叠加,并根据原料对机体的保健机制进行释放时序的控制,使该无抗畜类肠道保健剂的整体保健效果得以进一步提升。
本发明的目的之一是提供一种无抗畜类肠道保健剂的制备方法,该制备方法包括以下步骤:
S1. 分别制备微生态粉剂、抗菌肽粉剂、黏膜促进粉剂和中兽药粉剂;
S2. 将步骤S1中制备的微生态粉剂和抗菌肽粉剂以适当比例混合后,以靶向载体装载,制备微球粉体;
S3. 对步骤S1中制备的黏膜促进粉剂进行控释包衣,制备包衣粉体;
S4. 以适当比例混合步骤S2所制备的微粒粉体和步骤S3所制备的包衣粉体,对所得混合物进行二次包衣,制备肠溶微粒粉体;
S5. 以适当比例混合步骤S4所制备的肠溶微粒粉体和步骤S1所制备的中兽药粉剂,采用适当的辅料和工艺制备不同剂型。
本发明采用微生态粉剂、抗菌肽粉剂、黏膜促进粉剂和中兽药粉剂作为原料。上述原料中,微生态制剂能够通过调节动物肠道微生态平衡改善肠道健康状况的效果;抗菌肽由动物体内诱导产生,较之抗生素具有更高的选择性免疫激活和调节功能而无副作用;黏膜促进剂具有促进肠道黏膜发育和促进营养物质吸收的效果;中兽药制剂将中医理论应用于动物体,以调代治,在发病初期具有较好的延缓、控制效果,对正常肠道环境具有良好的维护效果。本发明通过上述四种原料的联用,制备了一种无抗的、对畜类肠道具有高效、稳定保健功能的制剂。
上述四种原料保健家畜肠道的机制各不相同,因此,本发明根据其作用机理,利用包衣技术对不同的原料进行控释处理,以保证各成分效力的充分发挥,以及成分间的协同作用。
本发明的制备工艺主要包括1次载药、2次包衣、3次混合(如图1所示):
①第一次混合:将微生态剂和抗菌肽成分进行混合;
②一次载药:采用靶向载体装载第一次混合所得混合物;
③第一次包衣:对黏膜促进粉剂进行控释包衣;
④第二次混合:将第一次载药所得粉体与第一次包衣所得粉体混合;
⑤第二次包衣:对第二次混合所得混合物进行肠溶包衣;
⑥第三次混合:将第二次包衣所得粉体与中兽药粉剂进行混合;
将第三次混合所得混合物作为主料,配合适当辅料和生产工艺,加工不同剂型的无抗畜类肠道保健剂。
其中,
第一次混合中,微生态剂和抗菌肽成分均具有调节微生态环境或免疫激活等能用于治疗家畜肠道病症的功能,采用靶向载体的一次载药,使上述两种成分能够于家畜肠道病灶处富集,从而保证该病灶处具有较高的制剂浓度,利用抗菌肽在该处诱导出较高的免疫活性物质以促进病灶恢复,同时,利用微生态制剂调节该处失衡的微生态环境以避免病灶反复发作。抗菌肽和微生态剂的配合联用,有利于加快病灶恢复速度;
第一次包衣使黏膜促进剂的释放延后于其他未行控释包衣的成分,其原因在于,黏膜促进剂对肠道黏膜的保护功能是通过对肠道黏膜进行大面积覆盖以及对黏膜表面物质的吸附分离而在肠道黏膜表面形成隔离环境,从而促进该处黏膜的自我修复和再生。由于黏膜促进剂具有较强的吸附性能,若其与其他成分同时释放,则不利于其他成分保健功能的充分发挥;
第二次混合和包衣处理的是第一次混合并靶向载药的微生态剂和抗菌肽成分与控释包衣后的黏膜促进剂,通过肠溶衣包衣保护上述三种成分不被家畜胃部消化,而能够进入肠道中释放;
第三次混合是将具有肠溶衣包衣保护的三种成分与中兽药剂进行混合,从而形成无抗畜类肠道保健剂的主要成分。中兽药剂有效成分多且复杂,其在机体内的扩散、作用途径极为多样,并不依赖于肠道内的富集,因此,无须对中兽药剂进行包衣处理,使该成分通过口腔、咽、食管、胃至肠道等整个消化道传药,以保证其药效的充分发挥,且有利于简化生产工艺、降低制备成本。
综上所述,本发明利用靶向载药、混合、包衣等技术,实现了微生态剂、抗菌肽、黏膜促进剂和中兽药剂等4种成分保健功能的彼此促进、协同配合,不仅保证了各成分对畜类肠道保健效果的充分发挥,同时,还通过成分功能的叠加、释放时序的控制使该保健剂的整体保健效果得以提升。
本发明中,微生态粉剂成分包括但不限于乳酸菌、芽孢杆菌、低聚木糖的一种或多种的混合物;
抗菌肽粉体成分包括一种或多种肽结构;
黏膜促进粉剂成分包括但不限于丁酸钠、谷氨酰胺中的一种或多种的混合物;
中兽药粉剂组方包括但不限于四君子汤;
其中,微生态粉剂和抗菌肽粉剂采用自制或购置的冻干粉剂;中兽药粉剂采用自制或购置的浸膏粉体。
本发明中,通过以下步骤制备微生态剂和抗菌肽的靶向载药体:
S21. 以适当的体积份数比混合微生态粉剂和抗菌肽粉剂,水溶制备菌体浓度不低于1х106cFU/ml的混悬液,并与适当体积的浓度为5mg/ml~8mg/ml的明胶混合;
S22. 以体积比0.1:0.05:1配置靶向剂、崩解剂与步骤A1所得的混和液,并与适当体积的浓度为2mg/ml~5mg/ml司盘80油相,混匀得乳浊液;
S23. 以适当比例混合步骤A2所得乳浊液与浓度为10%~20%的戊二醛溶液,低温静置不小于24h后,抽滤得滤饼;
S24. 依次使用乙醇和水洗涤步骤A3所得滤饼至无味后,烘干,并采用分样筛分选并收集目标粒径微球粉体。
本发明中,通过以下步骤制备黏膜促进剂控释粉体:
S31. 以适当比例混合黏膜促进粉剂、浓度5mg/ml~8mg/ml的明胶溶液和浓度2mg/ml~5mg/ml的司盘80,制备乳浊液;
S32. 以适当比例混合步骤S31所得乳浊液和浓度10%~20%的戊二醛溶液,低温静置不小于5h后,抽滤得滤饼;
S33. 依次使用乙醇和水洗涤步骤S32所得滤饼至无味后,烘干,采用分样筛分选并收集目标粒径微球;
S34. 以体积份数比1:(10~15)配置步骤S33所制备的微球粉体和缓释材料EudragitL100-55,以液体石蜡为增塑剂进行干法包衣,40℃烘干,采用分样筛分选并收集目标粒径的包衣粉体。
本发明中,通过以下步骤制备肠溶衣包衣粉体:
S41. 以适当比例混合步骤S2所制备的微粒粉体和步骤S3所制备的包衣粉体,制备混合微粒粉体;
S42. 以体积份数比1:(3~5)配置步骤S41所制备的混合微粒粉体和肠溶衣材料Eudragit L100,进行二次干法包衣,40℃烘干,采用分样筛分选并收集目标粒径的肠溶微粒粉体。
在上述制备方法的基础上,通过以下步骤可制备无抗畜类肠道保健颗粒剂:
S51. 以适当比例混合步骤S42所制备的肠溶微粒粉体和步骤S1所制备或购置的中兽药粉剂,制备混合粉体;
S52. 以适当比例混合步骤S51制备的混合粉体、鱼油和辅料,制备悬浊液;
S53. 采用喷雾冷冻制粒工艺处理步骤S52所制备的悬浊液,制备无抗畜类肠道保健颗粒剂。
本发明的微生态制剂、抗菌肽制剂、黏膜促进制剂和中兽药制剂等4种原料均具有生物活性,因此,在对其进行加工处理时,应严格控制工艺温度,并尽可能地选择低温成型工艺进行终产品剂型加工。
本发明的目的之二是提供一种无抗畜类肠道保健剂,其成分不含抗生素等抗菌药物,因此,长时间的饲喂不会影响畜类个体健康,也不会在畜类群体中产生残留、耐药、环境威胁等问题,从而提高动物福利、真正实现“无抗”养殖。
本发明的无抗畜类肠道保健剂,其主料是由一种复合微粒粉体和中兽药粉体形成的混合粉料。该复合微粒粉体结构如图2所示,其具有一包衣壳10,该包衣壳10中分布有若干第一微球颗粒20和若干第二微球颗粒30。第一微球颗粒20中装载有微生态制剂1、抗菌肽制剂2和少量的崩解剂3,该颗粒表面还具有若干特异性基团4。第二微球颗粒30中装载有黏膜促进剂5,该颗粒表面也具有一包衣壳体6。
其中,
包衣壳10为一肠溶衣包衣,能够在家畜的胃部内保持稳定而在肠道内溶解,从而保护其内部颗粒粉料不被胃部消化而富集于肠道中;
第一微球颗粒20表面的特异性基团4具有靶向畜类肠道炎症病灶的功能,通过特异性基团4靶向畜类肠道中的病灶,使第一微球颗粒20在该病灶处富集,从而提高了微球颗粒所装载的微生态制剂1和抗菌肽制剂2的利用率,以便加速病灶的恢复速度;
第一微球颗粒20中还含有少量的崩解剂3,该崩解剂3用于微生态制剂1和抗菌肽制剂2的快速释放,有利于提高上述两种制剂对畜类肠道的作用效率。
第二微球颗粒30的包衣壳体6为一控释包衣,能够长时间滞留于家畜肠道中并在较长时间内保持稳定,而使第二微球颗粒30装载的黏膜促进剂5滞后于其他原料成分释放进入肠道中。
本发明通过不同成型工艺加工得到不同剂型的无抗畜类肠道保健剂,剂型形态包括散剂、颗粒剂、片剂、口服液等药用剂型,也包括糖、饮料、饲料等食品形态。
附图说明
为了更清楚地说明本发明的技术方案,下面将对本说明书描述中所需要使用的附图作简单地介绍。
图1为本发明所采用的制备工艺示意图。
图2为本发明所制备的无抗畜类肠道保健剂中部分成分的结构示意图。
附图标记:10.包衣壳,20.第一微球颗粒,30.第二微球颗粒,1.微生态制剂,2.抗菌肽制剂,3.崩解剂,4.特异性基团,5.黏膜促进剂,6.包衣壳体。
具体实施方式
下文中仅简单地描述了某些示例性实施例。正如本领域技术人员可认识到的那样,在不脱离本发明申请实施例的精神或范围的情况下,可通过各种不同方式修改所描述的实施例。因此,本描述被认为本质上是示例性的而非限制性的。
实施例1
本实施例提供了一种无抗畜类肠道保健颗粒剂的制备方法,包括以下步骤:
1.分别购买或制备活菌数不小于108的乳酸菌粉剂、抗菌肽粉剂(与目标畜类同种诱导,如养殖畜类为猪时,可使用猪源抗菌肽PR-39)、丁酸钠粉体和兽用四君子汤粉体;
2.按体积份数比(5~10):1:(1~3)用水混合分散乳酸菌粉剂和猪源抗菌肽PR-39粉剂,制备菌体浓度不低于1х106cFU/ml的混悬液;
3.按体积份数比10:(1~3)将步骤2所得混悬液与浓度为(5~8)mg/ml的明胶溶液混合;
4.按体积份数比1:0.5:10将免疫磁珠、聚山梨酯80投入步骤3所得混合液中,混匀后,搅拌滴加适量浓度为(2~5)mg/ml的司盘80制备乳浊液;
5.按体积份数比1:(1~3)将步骤4所得乳浊液与浓度为10%~20%的戊二醛溶液混合,10℃以下静置24h后抽滤的滤饼;
6.依次使用乙醇和水洗涤步骤5所得滤饼至无味后,烘干、破碎,使用180目和220目分样筛分选粒径60μm~80μm微球粉体,采用HPLC法检测该微粉球体载药量为25.3%,包封率95.3%,符合要求,备用;
7.按体积份数比(1~3):10将丁酸钠粉剂与浓度为(5~8)mg/ml的明胶溶液混合,混匀后,搅拌滴加适量浓度为(2~5)mg/ml的司盘80制备乳浊液;
8.按体积份数比1:(1~3)将步骤7所得乳浊液与浓度为10%~20%的戊二醛溶液混合,10℃以下静置5h后抽滤的滤饼;
9.依次使用乙醇和水洗涤步骤8所得滤饼至无味后,烘干、破碎,使用200目和250目分样筛分选粒径65μm~75μm微球粉体,采用HPLC法检测该微球粉体载药量为17.0%,包封率97.4%,符合要求,备用;
10.按体积份数比1:(1~2)混合步骤6和步骤9所制得的两种微球粉体,再按体积份数比1:(3~5)将混合后的两种微球粉体与肠溶衣材料Eudragit L100进行混合,以液体石蜡为增塑剂进行干法包衣,40℃烘干;
11.使用40目和60目分样筛分选收集粒径250μm~380μm的粉体颗粒,采用HPLC法检测该微粒粉体载药量为52.7%,包封率96.1%,符合要求,备用;
12. 以质量份数比2:2:2:3:3:3:3:3:4:2.5配置党参、黄芪、山楂、白术、茯苓、泽泻、神曲、麦芽、五味子、山药、木通、甘草(四君子汤加味),煎煮30min~45min后,取汤液,浓缩制浸膏后,干燥至含水率小于4%,破碎、制粉,过60目筛得中兽药粉体;
13.按体积份数比(1~5):1混合步骤11所制得的微粒粉体与步骤12所制得的中兽药粉体,即得无抗畜类肠道保健颗粒剂原料;
14.按质量份数比(10~100):10:1向步骤13所制得的原料中混入鱼油和成型辅料,制备较为粘稠的悬浊液;
15.采用喷雾冷冻制粒工艺对步骤14所制得的悬浊液进行冷冻制粒,即得无抗畜类肠道保健颗粒剂,分装后,20℃以下储存。
本实施例所制备得到的无抗畜类肠道保健剂为颗粒制剂,使用其进行日常保健时,可将本颗粒制剂溶解于畜类饮用水中进行直饮,也可被用作一种添加剂,将本颗粒添加在日常饲料中。
实施例2
本实施例提供了一种无抗畜类肠道保健糖果的制备方法,包括以下步骤:
1.分别购买或制备总活菌数不小于108的乳酸菌和芽孢杆菌的混合粉剂、抗菌肽(可采用不同源物种,如天蚕素-B类抗菌肽)粉剂、谷氨酰胺粉体和兽用四君子汤粉体;
2.按体积份数比(5~10):1:(1~3)用水混合分散乳酸菌粉剂和天蚕素-B类抗菌肽粉剂,制备菌体浓度不低于1х106cFU/ml的混悬液;
3.按体积份数比10:(1~3)将步骤2所得混悬液与浓度为(5~8)mg/ml的明胶溶液混合;
4.按体积份数比1:0.5:10将免疫磁珠、聚山梨酯80投入步骤3所得混合液中,混匀后,搅拌滴加适量浓度为(2~5)mg/ml的司盘80制备乳浊液;
5.按体积份数比1:(1~3)将步骤4所得乳浊液与浓度为10%~20%的戊二醛溶液混合,10℃以下静置24h后抽滤的滤饼;
6.依次使用乙醇和水洗涤步骤5所得滤饼至无味后,烘干、破碎,使用180目和220目分样筛分选粒径60μm~80μm微球粉体,采用HPLC法检测该微粉球体载药量为30.9%,包封率95.8%,符合要求,备用;
7.按体积份数比(1~3):10将谷氨酰胺粉剂与浓度为(5~8)mg/ml的明胶溶液混合,混匀后,搅拌滴加适量浓度为(2~5)mg/ml的司盘80制备乳浊液;
8.按体积份数比1:(1~3)将步骤7所得乳浊液与浓度为10%~20%的戊二醛溶液混合,10℃以下静置5h后抽滤的滤饼;
9.依次使用乙醇和水洗涤步骤8所得滤饼至无味后,烘干、破碎,使用200目和250目分样筛分选粒径65μm~75μm微球粉体,采用HPLC法检测该微球粉体载药量为17.0%,包封率97.4%,符合要求,备用;
10.按体积份数比1:(1~2)混合步骤6和步骤9所制得的两种微球粉体,再按体积份数比1:(3~5)将混合后的两种微球粉体与肠溶衣材料Eudragit L100进行混合,以液体石蜡为增塑剂进行干法包衣,40℃烘干;
11.使用40目和60目分样筛分选收集粒径250μm~380μm的粉体颗粒,采用HPLC法检测该微粒粉体载药量为52.7%,包封率96.1%,符合要求,备用;
12. 以质量份数比2:2:2:3:3:3:3:3:4:2.5配置党参、黄芪、山楂、白术、茯苓、泽泻、神曲、麦芽、五味子、山药、木通、甘草(四君子汤加味),煎煮30min~45min后,取汤液,浓缩制浸膏后,干燥至含水率小于4%,破碎、制粉,过60目筛得中兽药粉体;
13.按体积份数比(1~5):1混合步骤11所制得的微粒粉体与步骤12所制得的中兽药粉体,即得无抗畜类肠道保健糖果主料;
14.按质量份数比1:(1~15)向步骤13所制得的主料中混入精制糖粉,以及必要量的明胶作为粘合剂,采用冷加工工艺对上述原料进行压片成型,制得压片糖果,封装后,20℃以下储存。
本实施例所制备得到的无抗畜类肠道保健剂的形式为糖果,通过在步骤14处调整主料与精制糖粉、明胶等辅料的配比,可制备得到不同保健功效的糖果产品,以进行日常保健或疾病护理。由于本糖果甜度高,猪、马等对甜味敏感的畜类更易于接收而便于饲喂。
Claims (10)
1.无抗畜类肠道保健剂的制备方法,其特征在于,包括以下步骤:
S1. 分别制备微生态粉剂、抗菌肽粉剂、黏膜促进粉剂和中兽药粉剂;
S2. 将步骤S1中制备的微生态粉剂和抗菌肽粉剂以适当比例混合后,以靶向载体装载,制备微球粉体;
S3. 对步骤S1中制备的黏膜促进粉剂进行控释包衣,制备包衣粉体;
S4. 以适当比例混合步骤S2所制备的微粒粉体和步骤S3所制备的包衣粉体,对所得混合物进行二次包衣,制备肠溶微粒粉体;
S5. 以适当比例混合步骤S4所制备的肠溶微粒粉体和步骤S1所制备的中兽药粉剂,采用适当的辅料和工艺制备不同剂型。
2.根据权利要求1所述的制备方法,其特征在于,步骤S2具体包括:
S21. 以适当的体积份数比混合微生态粉剂和抗菌肽粉剂,水溶制备菌体浓度不低于1х106cFU/ml的混悬液,并与适当体积的浓度为5mg/ml~8mg/ml的明胶混合;
S22. 以体积比0.1:0.05:1配置靶向剂、崩解剂与步骤A1所得的混和液,并与适当体积的浓度为2mg/ml~5mg/ml司盘80油相,混匀得乳浊液;
S23. 以适当比例混合步骤A2所得乳浊液与浓度为10%~20%的戊二醛溶液,低温静置不小于24h后,抽滤得滤饼;
S24. 依次使用乙醇和水洗涤步骤A3所得滤饼至无味后,烘干,并采用分样筛分选并收集目标粒径微球粉体。
3.根据权利要求2所述的制备方法,其特征在于,步骤S24所制备的微球粉体中微球对微生态成分和抗菌肽成分的载药量均不小于10%、包封率不小于95%。
4.根据权利要求1所述的制备方法,其特征在于,步骤S3具体包括:
S31. 以适当比例混合黏膜促进粉剂、浓度5mg/ml~8mg/ml的明胶溶液和浓度2mg/ml~5mg/ml的司盘80,制备乳浊液;
S32. 以适当比例混合步骤S31所得乳浊液和浓度10%~20%的戊二醛溶液,低温静置不小于5h后,抽滤得滤饼;
S33. 依次使用乙醇和水洗涤步骤S32所得滤饼至无味后,烘干,采用分样筛分选并收集目标粒径微球;
S34. 以体积份数比1:(10~15)配置步骤S33所制备的微球粉体和缓释材料EudragitL100-55,以液体石蜡为增塑剂进行干法包衣,40℃烘干,采用分样筛分选并收集目标粒径的包衣粉体。
5.根据权利要求4所述的制备方法,其特征在于,步骤S33所制备的微球的载药量不小于10%、包封率不小于95%。
6.根据权利要求1所述的制备方法,其特征在于,步骤S4具体包括:
S41. 以适当比例混合步骤S2所制备的微粒粉体和步骤S3所制备的包衣粉体,制备混合微粒粉体;
S42. 以体积份数比1:(3~5)配置步骤S41所制备的混合微粒粉体和肠溶衣材料Eudragit L100,进行二次干法包衣,40℃烘干,采用分样筛分选并收集目标粒径的肠溶微粒粉体。
7.根据权利要求1所述的制备方法,其特征在于,步骤S5具体包括:
S51. 以适当比例混合步骤S4所制备的肠溶微粒粉体和步骤S1所制备的中兽药粉剂,制备混合粉体;
S52. 以适当比例混合步骤S51制备的混合粉体、鱼油和辅料,制备悬浊液;
S53. 采用喷雾冷冻制粒工艺处理步骤S52所制备的悬浊液,制备无抗畜类肠道保健颗粒剂。
8.根据权利要求1~7中任意一项所述的制备方法,其特征在于,
微生态粉剂成分包括但不限于乳酸菌、芽孢杆菌、低聚木糖的一种或多种的混合物;
抗菌肽粉体成分包括一种或多种肽结构;
黏膜促进粉剂成分包括但不限于丁酸钠、谷氨酰胺中的一种或多种的混合物;
中兽药粉剂组方包括但不限于四君子汤;
其中,
微生态粉剂和抗菌肽粉剂采用自制或购置的冻干粉剂;
中兽药粉剂采用自制或购置的浸膏粉体。
9.无抗畜类肠道保健剂,其特征在于,由权利要求1~8中任意一项的制备方法制备而成。
10.根据权利要求9所述的保健剂,其特征在于,该保健剂的形态包括药用剂型和食品形态。
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1554328A (zh) * | 2003-12-25 | 2004-12-15 | 浙江大学 | 肠定向释药的微球制剂及其制备方法 |
US20140056980A1 (en) * | 2012-04-30 | 2014-02-27 | Tillotts Pharma Ag | Delayed release drug formulation |
CN104546907A (zh) * | 2014-12-24 | 2015-04-29 | 浙江惠嘉生物科技有限公司 | 一种肠溶纳米氧化锌制剂及其制备方法 |
CN105410338A (zh) * | 2015-12-17 | 2016-03-23 | 百洋产业投资集团股份有限公司 | 无抗仔猪日粮及其制备方法 |
CN105963688A (zh) * | 2016-06-23 | 2016-09-28 | 四川英格瑞生物科技有限公司 | 一种治疗仔猪肠道疾病与提高免疫力的粉剂及其制备方法 |
CN109984276A (zh) * | 2019-04-26 | 2019-07-09 | 山东祥维斯生物科技股份有限公司 | 一种调理肠道应激反应的无抗饲料添加剂及其制备方法 |
CN110897048A (zh) * | 2019-12-30 | 2020-03-24 | 广州格雷特生物科技有限公司 | 一种肠溶丁酸钠微囊及其制备方法和应用 |
CN110923170A (zh) * | 2019-12-18 | 2020-03-27 | 福建大用投资有限公司 | 一种用于生猪无抗养殖立体防疫的复合微生态制剂及其制备方法和应用 |
-
2020
- 2020-05-11 CN CN202010392300.4A patent/CN111567678A/zh active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1554328A (zh) * | 2003-12-25 | 2004-12-15 | 浙江大学 | 肠定向释药的微球制剂及其制备方法 |
US20140056980A1 (en) * | 2012-04-30 | 2014-02-27 | Tillotts Pharma Ag | Delayed release drug formulation |
CN104546907A (zh) * | 2014-12-24 | 2015-04-29 | 浙江惠嘉生物科技有限公司 | 一种肠溶纳米氧化锌制剂及其制备方法 |
CN105410338A (zh) * | 2015-12-17 | 2016-03-23 | 百洋产业投资集团股份有限公司 | 无抗仔猪日粮及其制备方法 |
CN105963688A (zh) * | 2016-06-23 | 2016-09-28 | 四川英格瑞生物科技有限公司 | 一种治疗仔猪肠道疾病与提高免疫力的粉剂及其制备方法 |
CN109984276A (zh) * | 2019-04-26 | 2019-07-09 | 山东祥维斯生物科技股份有限公司 | 一种调理肠道应激反应的无抗饲料添加剂及其制备方法 |
CN110923170A (zh) * | 2019-12-18 | 2020-03-27 | 福建大用投资有限公司 | 一种用于生猪无抗养殖立体防疫的复合微生态制剂及其制备方法和应用 |
CN110897048A (zh) * | 2019-12-30 | 2020-03-24 | 广州格雷特生物科技有限公司 | 一种肠溶丁酸钠微囊及其制备方法和应用 |
Non-Patent Citations (2)
Title |
---|
梁建友;王元有;: "金雀异黄素靶向明胶微球的制备与表征" * |
苏诗娜;吕竹芬;梁超峰;卢克伟;黄韵然;陈燕忠;: "新辅料和新技术在结肠定位制剂中的应用" * |
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