CN105246460A - 消旋卡多曲类脂组合物 - Google Patents
消旋卡多曲类脂组合物 Download PDFInfo
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- CN105246460A CN105246460A CN201480015975.XA CN201480015975A CN105246460A CN 105246460 A CN105246460 A CN 105246460A CN 201480015975 A CN201480015975 A CN 201480015975A CN 105246460 A CN105246460 A CN 105246460A
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- racecadotril
- oil
- surfactant
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- 239000004094 surface-active agent Substances 0.000 claims abstract description 31
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- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
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Abstract
本发明提供了一种包含消旋卡多曲、至少一种表面活性剂和类脂的类脂组合物。
Description
背景技术
技术领域
本发明涉及类脂/微乳液组合物。更具体地,本发明涉及包含药物活性物质成分的基于类脂/微乳液组合物以及制备所述组合物的方法。
相关的背景技术
痢疾是一种肠道疾病,其特征在于水样大便频率的增加。它可能是多种原因所引起,其包括细菌或病毒引发的痢疾。由过敏或诸如多脂或辛辣食物的食物消耗引起的食物不耐受可导致痢疾。食物中毒也可导致痢疾。在一些情况下,痢疾可为其他病症和疾病的症状。
痢疾是肠道或其他身体机能疾病的症状。可以服用各种处方和非处方药物用于减轻痢疾。然而,这些药物中的许多药物在减轻痢疾的同时具有一些副作用。
消旋卡多曲也用于治疗痢疾。它减少(i)分泌过多的水和电解液进入肠内腔,(ii)急性痢疾的发病率和持续时间和(iii)痢疾相关联的症状。
消旋卡多曲是一种具有较差溶解度和较差口服生物利用率的药物活性物质成分。目前,消旋卡多曲以固体口服剂型使用。
发明内容
本发明涉及包含消旋卡多曲、至少一种表面活性剂和类脂的微乳液组合物。
在一个实施方案中,本发明的微乳液组合物包含约0.01重量%至约24.0重量%的消旋卡多曲、共约1重量%至约95重量%的表面活性剂和约0.01重量%至约60重量%的类脂,其中每个重量%均基于100ml的组合物计。
本发明还包括用于治疗患有痢疾的受检者的方法,其包括受检者口服包含消旋卡多曲、至少一种表面活性剂和类脂的组合物的步骤。
具体实施方式
如本文所用,“微乳液”是指类脂、水和至少一种表面活性剂的液体混合物。微乳液的特征在于它的澄清、热力学稳定和各向同性的外观。
如本文所用,“稳定”是指组合物对肉眼澄清且基本上不含消旋卡多曲的化学降解、基本的颜色变化、浊度或油性小珠。在40℃下,至少约3个月在含水和/或非水的组分中不应观察到相分离。更优选地,在40℃下,至少约6个月在含水和/或非水的组分中不应观察到相分离。在一个实施方案中,当在40℃下保存3个月时,基于消旋卡多曲的总的重量百分比(重量%)计,消旋卡多曲的总化学降解产物应少于0.5重量%,例如少于0.2重量%。在另一个实施方案中,当在40℃下保存6个月时,基于消旋卡多曲的总的重量百分比(重量%)计,消旋卡多曲的总化学降解产物应少于0.5重量%,例如少于0.2重量%。
如本文所用,“自微乳化药物递送体系”(SMEDDS)为油、表面活性剂和有时潜溶剂的混合物。SMEDDS可用于制剂体系,以改善高度亲脂化合物的口服吸收。当引入到水相中时,SMEDDS自发地使用温和搅拌乳化以产生细小的水包油乳液。在SMEDDS中的药物以小液滴尺寸出现,并表现出增大的溶解和渗透性。可配制SMEDDS以供液体或固体形式使用。以固体形式使用时,固体包封在胶囊剂或片剂中。由于速度的感知、药物组合物的视觉外观和便于吞咽,液体填充的或半固体填充的胶囊剂是某些消费者优选的剂型。
本发明为包含消旋卡多曲、至少一种表面活性剂和类脂的微乳液组合物。
各种研究表明消旋卡多曲能够有效减少痢疾的症状。消旋卡多曲优于其他药物的一个益处在于消旋卡多曲被证明具有较少的副作用,诸如治疗后便秘。
消旋卡多曲具有较低的水中溶解度,在室温条件下为约10微克/毫升。在本发明的组合物中,消旋卡多曲可溶解在微乳液中。
消旋卡多曲以每100ml的乳液组合物约0.01重量%至约24.0重量%的量包含在微乳液组合物中。优选地,消旋卡多曲为每100ml的乳液组合物约0.01重量%至约18.0重量%,更优选地,约0.01重量%至约12.0重量%,并且甚至更优选地,每100ml的乳液组合物约0.01重量%至约10.0重量%。在一个实施方案中,消旋卡多曲为每100ml的乳液组合物约4.0重量%至约24.0重量%。在另一个实施方案中,消旋卡多曲为每100ml的乳液组合物约4.0重量%至约18.0重量%。在又一个实施方案中,消旋卡多曲为每100ml的乳液组合物约4.0重量%至约12.0重量%。在又一个实施方案中,消旋卡多曲为每100ml的乳液组合物约4.0重量%至约10.0重量%。
本发明的微乳液组合物包含至少一种表面活性剂。表面活性剂可为(例如)非离子表面活性剂、阳离子表面活性剂、阴离子表面活性剂或它们的混合物。
合适的表面活性剂包括(例如)具有小于12的亲水性亲脂平衡(HLB)值的水不溶性表面活性剂和具有大于12的HLB值的水可溶性表面活性剂。具有高HLB和亲水性的表面活性剂有助于油-水液滴的形成。表面活性剂实质上为两亲性的并且能够溶解或增溶相对高含量的疏水性药物化合物。
非限制性例子包括吐温、二甲基乙酰胺(DMA)、二甲基亚砜(DMSO)、乙醇、甘油、N-甲基-2-吡咯烷酮(NMP)、PEG300、PEG400、泊洛沙姆407、丙二醇、磷脂、氢化大豆磷脂酰胆碱(HSPC)、二硬脂酰磷脂酰甘油(DSPG)、L-α-二肉豆蔻酰磷脂酰胆碱(DMPC)、L-α-二肉豆寇酰磷脂酰甘油(DMPG)、聚乙二醇35蓖麻油(CREM0PH0REL,CREM0PH0RELP)、聚乙二醇40氢化蓖麻油(CremophorRH40)、聚乙二醇60氢化蓖麻油(CREMOPHORRH60)、聚山梨醇酯20(TWEEN20)、聚山梨醇酯80(TWEEN80)、d-α-生育酚聚乙二醇1000琥珀酸酯(TPGS)、SolutolHS-15、脱水山梨糖醇单油酸酯(SPAN20)、PEG300辛酸/癸酸甘油酯(S0FTIGEN767)、PEG400辛酸/癸酸甘油酯(LABRAS0L)、PEG300油酸甘油酯(LABRAFILM-1944CS)、聚乙二醇35蓖麻油(ETOCAS35)、辛酸甘油酯(甘油单酯和甘油二酯)(IMWITOR)、PEG300亚油酸甘油酯(LABRAFILM-2125CS)、聚乙二醇8硬脂酸酯(PEG400单硬脂酸酯)、聚乙二醇40硬脂酸酯(PEG1750单硬脂酸酯)、薄荷油以及它们的组合。
另外,合适的表面活性剂包括(例如)脱水山梨糖醇单月桂酸酯的聚氧乙烯衍生物,诸如聚山梨醇酯、辛酸癸酸聚乙二醇甘油酯、聚乙二醇化甘油酯等。
在一个实施方案中,表面活性剂为聚乙二醇35蓖麻油和辛酸甘油酯(甘油单酯和甘油二酯)NF的组合。
在本发明的组合物中,表面活性剂的总重量百分比为每100ml的微乳液组合物约1重量%至约95重量%。优选地,表面活性剂为每100ml的微乳液组合物约25重量%至约95重量%,并且更优选地,约30重量%至约90重量%。在一个实施方案中,表面活性剂为每100ml的微乳液组合物约45重量%至约95重量%。
类脂为本发明组合物的另一种基本组分。类脂有助于增溶消旋卡多曲,并且还促进自乳化过程。合适的类脂包括(例如)植物油(改性的和/或水解的)、具有不同饱和度的长链甘油三酯和中链甘油三酯,并且可使用它们的组合。
另外,亲脂且不溶于水的甘油单酯、甘油二酯和/或甘油三酯乳化剂(脂肪和油)(购自Abitec公司,以商品名出售)可用作类脂。例如,蜂蜡、油酸、大豆脂肪酸、d-α-生育酚(维生素E)、玉米油单-二-三甘油二酯、中链(C8/C10)甘油单酯和甘油二酯、长链甘油三酯、蓖麻油、玉米油、棉籽油、橄榄油、花生油、薄荷油、红花油、芝蔴油、大豆油、氢化大豆油、氢化植物油、中链甘油三酯、来源于椰子油的辛酸/癸酸甘油三酯、棕榈种子油以及它们的组合。
类脂以每100ml的乳液组合物约0.01重量%至约60重量%的量包含在组合物中。优选地,类脂为约0.01重量%至约50重量%。在另一个实施方案中,类脂为每100ml的乳液组合物约1重量%至约20重量%,更优选地,每100ml的乳液组合物约1重量%至约15重量%,并且甚至更优选地,每100ml的乳液组合物约1重量%至约10重量%。在一个具体实施方案中,类脂为每100ml的乳液组合物约1重量%至约2重量%。
希望使组合物中的含水量最小化。组合物中的含水量将主要地由包含在组合物中的每种组分的含水量决定。在一个实施方案中,基于组合物的总重量%计,组合物的含水量小于约3.5重量%。在另一个实施方案中,基于组合物的总重量%计,组合物的含水量小于约2.5重量%。在又一个实施方案中,基于组合物的总重量%计,组合物的含水量小于约0.5重量%。在又一个实施方案中,基于组合物的总重量%计,组合物的含水量小于约0.2重量%。
任选地,本发明的乳液组合物中可包含多种成分。
适用于食品或药学产品的任何着色剂均可在本发明中使用。典型的着色剂包括(例如)偶氮染料、喹啉酮(quinopthalone)染料、三苯甲烧染料、咕吨类染料、靛青类染料、氧化铁、氢氧化铁、二氧化钛、天然染料以及它们的混合物。更具体地讲,合适的着色剂包括但不限于专利蓝V、酸性亮绿BS、红2G、偶氮玉红、丽春红4R、苋菜红、D&C红33、D&C红22、D&C红26、D&C红28、D&C黄10、FD&C黄5、FD&C黄6、FD&C红3、FD&C红40、FD&C蓝1、FD&C蓝2、FD&C绿3、亮黑BN、炭黑、氧化铁黑、氧化铁红、氧化铁黄、二氧化钛、核黄素、胡萝卜烯类、花青素类、姜黄、胭脂虫提取物、叶绿酸、角黄素、焦糖、甜菜红苷以及它们的混合物。
相似地,乳液组合物中可包含风味剂。添加到组合物中的风味剂的量依赖于期望的口感特征。
组合物可包含其他成分或组分,诸如芳香剂;甜味剂,诸如三氯蔗糖、山梨醇、高果糖玉米糖浆、糖等等;粘度调节剂,诸如黄原胶;防腐剂,诸如苯甲酸钠NF,缓冲剂,诸如柠檬酸和/或氯化钠;或它们的混合物。
本发明的乳液组合物可通过本领域技术人员已知的任何方法制备,只要得到期望的组合物即可。
合适的方法包括(例如)在混合壶中混合每个成分,其中这些成分可相继地或以任何方式添加,只要实现预期的结果即可。此外,混合作用应足以将每个成分掺入组合物中。
评价乳液稳定性的主要方法基于分析的降解分析。通过测定乳化速率、液滴尺寸分布和浊度测量可估测自乳化的效率。
另外,可通过测量乳液的浊度来评估稳定性。该评估有助于确定乳液是否快速地并在可再现的时间内达到平衡。
还通过检查过饱和(沉淀)来评估稳定性。通过将1ml的制剂置于具有250ml0.1NHCL的烧杯中进行测试。如果形成沉淀,那么体系是过饱和的。
在本发明的一个实施方案中,微乳液组合物作为用于直接口服消耗的包封乳液施用。在另一个实施方案中,微乳液组合物以包含微乳液组合物的口服软明胶胶囊施用。在又一个实施方案中,微乳液组合物以包含微乳液组合物的多个微凝胶珠施用。在又一个实施方案中,微乳液组合物以包含微乳液组合物的硬明胶胶囊施用。当微乳液组合物包含在硬明胶胶囊中时,硬明胶胶囊可为带状的。在又一个实施方案中,微乳液组合物以包含微乳液组合物的栓剂或灌肠剂施用。
任选地,本发明的微乳液组合物包含第二活性成分。在一个实施方案中,第二活性成分为助消化***健康的活性成分。非限制性例子包括(例如)泻药、抗酸剂、质子泵抑制剂、抗气剂、止吐药、H2阻滞剂或第二止泻药剂。
在一个实施方案中,第二活性成分掺入到微乳液基质中。在另一个实施方案中,第二活性成分存在于与微乳液组合物分开的剂型组合物的另一部分中。在又一个实施方案中,第二活性成分被装入微囊。
合适的抗气剂包括但不限于二甲基硅油。
合适的另外的止泻药剂包括但不限于洛派丁胺。
在一个实施方案中,本发明的微乳液组合物包含约8.0重量%至约10.0重量%的消旋卡多曲、共约88重量%至约91重量%的表面活性剂、约1重量%至约2重量%的类脂,其中每个重量%均基于100ml的组合物计。
在另一个实施方案中,本发明的微乳液组合物包含约0.01重量%至约24.0重量%的消旋卡多曲、共约1重量%至约95重量%的表面活性剂、约0.01重量%至约60重量%的类脂,其中每个重量%均基于100ml的组合物计。
在又一个实施方案中,本发明的微乳液组合物包含约3.0重量%至约7.0重量%的消旋卡多曲、共约40重量%至约53重量%的表面活性剂、约40重量%至约53重量%的类脂,其中每个重量%均基于100ml的组合物计。
本发明的微乳液组合物可在任何合适的递送体系中递送。例如,在一个实施方案中,微乳液组合物经口服递送。在另一个实施方案中,微乳液组合物以软外壳剂型递送。在又一个实施方案中,微乳液组合物以硬外壳剂型递送。在又一个实施方案中,片剂剂型用于递送微乳液组合物。
本发明还包括用于治疗患有痢疾的受检者的方法,其包括受检者口服包含消旋卡多曲、至少一种表面活性剂和类脂的组合物的步骤。
以下提供的实例进一步说明了本发明的组合物和方法。应当理解,本发明不限于所述的实例。
实例1
浓缩的消旋卡多曲类脂组合物:用于液体填充的明胶胶囊中
表1:基于消旋卡多曲类脂的组合物占组合物的百分比:甘油三酯型1
1.可以35USP/NF、EP、JP从CRODAHealthcare商购获得
2.可以988USP/NF、EP、JP从CREMER商购获得
3.可以810N(辛酸/癸酸甘油三酯;70:30/C8:C10)USP/NF、EP、JP从CRHMER商购获得
表2:基于消旋卡多曲类脂的组合物占组合物的百分比:甘油三酯型2
1.可以35USP/NF、EP、JP从CRODAHealthcare商购获得
2.可以988USP/NF、EP、JP从CREMER商购获得
3.可以812N(辛酸/癸酸甘油三酯;60:40/C8:C10)USP/NF、EP、JP从CRHMER商购获得
利用表1和表2中的材料,采取下列混合步骤以形成微乳液。共制备了6个包括3个比率的混合物,其中每个用MIGLYOL810N(表1)和MIGLYOL812N(表2)制备。
步骤1:在合适的容器中,以下列重量比率用三个独立的混合物制备聚乙二醇35蓖麻油(35)、辛酸甘油酯(988)和中链甘油三酯(810N&812N)的混合物:88:10:2(比率1)、58:40:2(比率2)和30:68:2(比率3)。
步骤2:利用涡旋搅拌器混合来自步骤1的混合物。
步骤3:利用涡旋搅拌器将消旋卡多曲缓慢地加入到来自步骤2的混合物中并且混合5分钟。
步骤4:将来自步骤3的混合物放置在实验室摇动器中并且混合36小时直至形成澄清溶液。
消旋卡多曲类脂制剂的稳定性
当在40℃下密封的瓶中保存3个月时,针对消旋卡多曲降解,检测实例1中制备的制剂的化学稳定性,并示于表3中。
*:制剂:
1.88%超精制35、10%Imwitor988、2%Miglyol810N(比率1)
2.88%超精制35、10%Imwitor988、2%Miglyol812N(比率1)
3.58%超精制35、40%Imwitor988、2%Miglyol810N(比率2)
4.58%超精制35、40%Imwitor988、2%Miglyol812N(比率2)
5.30%超精制35、68%Imwitor988、2%Miglyol810N(比率3)
6.30%超精制35、68%Imwitor988、2%Miglyol812N(比率3)
ND–未检出
成分:
A.超精制Etocas35(NF,EP,JP):
由CRODAHealthCare制造
聚乙二醇35蓖麻油
HLB值14
B.Imwitor988:中链偏甘油酯
由CREMER制造
辛酸甘油酯(甘油单酯和甘油二酯)
熔点约25℃
HLB值4
C.Imwitor742:中链偏甘油酯
由CREMER制造
辛酸/癸酸甘油酯
熔点约25℃
HLB值3-4
D.Miglyol:中链甘油三酯(MCT油,分级椰子油)
由CREMER制造
辛酸(C8)/癸酸(ClO)甘油三酯
810N-70:30C8/C10共混物
812N-60:40C8/C10共混物
基于各种制剂的密度的转化率:
制剂1/制剂2:1.042g/ml
制剂3/制剂4:1.028g/ml
制剂5/制剂6:1.016g/ml
含水量(%重量/重量):
制剂 | 含水量(%重量/重量) |
1 | 0.02 |
2 | 0.02 |
3 | 0.08 |
4 | 0.08 |
5 | 0.13 |
6 | 0.13 |
7 | 0.09 |
8 | 0.09 |
9 | 0.10 |
10 | 0.10 |
实例2
浓缩的消旋卡多曲类脂组合物:用于液体填充的明胶胶囊中
表4:
成分 | 制剂7(%w/w) a | 制剂8(%w/w) |
消旋卡多曲 | 4.61 | 4.25 |
辛酸甘油酯(甘油单酯和甘油二酯)NF1 | 47.95 | 48.00 |
中链甘油三酯2 | 47.44 | - |
中链甘油三酯3 | - | 47.75 |
总计 | 100 | 100 |
消旋卡多曲测定(mg/mL) | 46.11 | 42.49 |
1.可以USP/NF、EP、JP从CREMER商购获得
2.可以810N(辛酸/癸酸甘油三酯;70:30/C8:C10)USP/NF、EP、JP从CRHMER商购获得
3.可以812N(辛酸/癸酸甘油三酯;60:40/C8:C10)USP/NF、EP、JP从CRHMER商购获得
表5:
成分 | 制剂9(51.5:48.5) a | 制剂10(51.4:48.6) |
消旋卡多曲 | 5.28 | 5.59 |
辛酸甘油酯(甘油单酯和甘油二酯)NF1 | 48.83 | 48.54 |
中链甘油三酯2 | 45.90 | - |
中链甘油三酯3 | - | 45.87 |
总计 | 100 | 100 |
消旋卡多曲测定(mg/mL) | 52.78 | 55.93 |
1.可以USP/NF、EP、JP从CREMER商购获得
2.可以810N(辛酸/癸酸甘油三酯;70:30/C8:C10)USP/NF、EP、JP从CRHMER商购获得
3.可以812N(辛酸/癸酸甘油三酯;60:40/C8:C10)USP/NF、EP、JP从CRHMER商购获得
测试方法:
样品制备:(在乙腈中)
1.移取1ml消旋卡多曲类脂溶液至100ml容量瓶(V.F.)中
2.用乙腈稀释至刻度。如有必要,加入约20ml二甲基乙酰胺。
3.如有必要,用乙腈将样品溶液进一步稀释至约0.1mg/mL。
样品分析
在类似于下文建议的条件下,将参比标样(0.1mg/mL消旋卡多曲的乙腈溶液)和样品进样至合适的HPLC***中。可修改参数以优化色谱。
通过比较检测得到的样品溶液中消旋卡多曲的峰面积与标准溶液中消旋卡多曲的峰面积,来测定消旋卡多曲。通过相对于消旋卡多曲色谱峰的%峰面积来测定降解产物含量。
色谱条件(欧洲药典消旋卡多曲方法):
梯度表:
时间(min) | 流速 | %A | %B |
初始 | 1.0 | 60 | 40 |
5 | 1.0 | 60 | 40 |
25 | 1.0 | 20 | 80 |
35 | 1.0 | 20 | 80 |
36 | 1.0 | 60 | 40 |
45 | 1.0 | 60 | 40 |
流动相A:磷酸盐缓冲液,pH2.5(缓冲液制备:将1g磷酸二氢钾溶解于水中,用磷酸将pH调节至2.5,用水稀释至1000ml)
流动相B:100%乙腈
虽然上面已经参照本发明的具体实施方案描述了本发明,但是应意识到,可作出的不偏离本文公开的创造性概念的很多改变、修改形式和变形形式是显而易见的。因此,旨在包括落在所附权利要求的精神和宽范围内的所有这样的改变、修改形式和变形形式。本文引用的所有专利申请、专利及其他出版物全文以引用方式并入本文。
Claims (18)
1.一种微乳液组合物,包含:
消旋卡多曲、至少一种表面活性剂和类脂。
2.根据权利要求1所述的组合物,其中所述组合物为自乳化体系。
3.根据权利要求1所述的组合物,其中所述组合物在40℃下稳定约3个月。
4.根据权利要求1所述的组合物,其中所述表面活性剂选自:非离子的、阳离子的、阴离子的、以及它们的混合物。
5.根据权利要求1所述的组合物,其中所述表面活性剂选自:吐温、二甲基乙酰胺(DMA)、二甲基亚砜(DMSO)、乙醇、甘油、N-甲基-2-吡咯烷酮(NMP)、PEG300、PEG400、泊洛沙姆407、丙二醇、磷脂、氢化大豆磷脂酰胆碱(HSPC)、二硬脂酰磷脂酰甘油(DSPG)、L-α-二肉豆蔻酰磷脂酰胆碱(DMPC)、L-α-二肉豆寇酰磷脂酰甘油(DMPG)、聚乙二醇35蓖麻油(CREMOPHOREL,CREMOPHORELF)、聚乙二醇40氢化蓖麻油(CremophorRH40)、聚乙二醇60氢化蓖麻油(CREMOPHORRH60)、聚山梨醇酯20(TWEEN20)、聚山梨酸酯80(TWEEN80)、d-α-生育酚聚乙二醇1000琥珀酸酯(TPGS)、SolutolHS-15、脱水山梨糖醇单油酸酯(SPAN20)、PEG300辛酸/癸酸甘油酯(SOFTIGEN767)、PEG400辛酸/癸酸甘油酯(LABRASOL)、PEG300油酸甘油酯(LABRAFILM-1944CS)、PEG300亚油酸甘油酯(LABRAFILM-2125CS)、聚乙二醇35蓖麻油(ETOCAS35)、辛酸甘油酯(甘油单酯和甘油二酯)(IMWITOR)、聚乙二醇8硬脂酸酯(PEG400单硬脂酸酯)、聚乙二醇40硬脂酸酯(PEG1750单硬脂酸酯)、脱水山梨糖醇单月桂酸酯的聚氧乙烯衍生物诸如聚山梨醇酯、辛酸癸酸聚乙二醇甘油酯、聚乙二醇化甘油酯、以及它们的混合物。
6.根据权利要求1所述的组合物,其中所述至少一种表面活性剂以每100ml的所述乳液组合物总共约1重量%至约95重量%的量存在。
7.根据权利要求1所述的组合物,其中所述类脂选自:植物油(改性的和/或水解的)、具有不同饱和度的长链甘油三酯和中链甘油三酯、亲脂且不溶于水的甘油单酯、甘油二酯和/或甘油三酯乳化剂(脂肪和油)、蜂蜡、油酸、大豆脂肪酸、d-α-生育酚(维生素E)、玉米油单-二-三甘油二酯、中链(C8/C10)甘油单酯和甘油二酯、长链甘油三酯、蓖麻油、玉米油、棉籽油、橄榄油、花生油、薄荷油、红花油、芝麻油、大豆油、氢化大豆油、氢化植物油、中链甘油三酯、来源于椰子油的辛酸/癸酸甘油三酯、棕榈种子油、以及它们的混合物。
8.根据权利要求1所述的组合物,其中所述类脂以每100ml的所述乳液组合物约0.01重量%至约20重量%的量存在。
9.根据权利要求1所述的组合物,还包含选自缓冲剂、防腐剂、甜味剂、粘度调节剂、着色剂、芳香剂、风味剂以及它们的混合物的任选成分。
10.根据权利要求1所述的组合物,还包含选自黄原胶、柠檬酸、苯甲酸钠、三氯蔗糖、风味剂以及它们的混合物的任选成分。
11.一种微乳液组合物,包含:
约0.10重量%至约24.0重量%的消旋卡多曲;
总共约1重量%至约95重量%的表面活性剂;和
约0.01重量%至约20重量%的类脂;
其中每个重量%基于100ml的所述组合物计。
12.根据权利要求1所述的组合物,其中所述组合物具有基于所述组合物总重量计小于约3.5重量%的总含水量。
13.一种包含根据权利要求1所述的组合物的软外壳剂型。
14.一种包含根据权利要求1所述的组合物的硬外壳剂型。
15.一种包含根据权利要求1所述的组合物的片剂剂型。
16.根据权利要求11所述的组合物,其中所述组合物在40℃下稳定约3个月。
17.一种微乳液组合物,包含:
约3.0重量%至约7.0重量%的消旋卡多曲;
总共约40重量%至约53重量%的表面活性剂;和
约40重量%至约53重量%的类脂;
其中每个重量%基于100ml的所述组合物计。
18.一种用于治疗患有痢疾的受检者的方法,包括受检者口服包含消旋卡多曲、至少一种表面活性剂和类脂的组合物的步骤。
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