CN1850086A - 左旋吗啉硝唑在制备抗寄生虫感染药物中的用途 - Google Patents
左旋吗啉硝唑在制备抗寄生虫感染药物中的用途 Download PDFInfo
- Publication number
- CN1850086A CN1850086A CN 200610083198 CN200610083198A CN1850086A CN 1850086 A CN1850086 A CN 1850086A CN 200610083198 CN200610083198 CN 200610083198 CN 200610083198 A CN200610083198 A CN 200610083198A CN 1850086 A CN1850086 A CN 1850086A
- Authority
- CN
- China
- Prior art keywords
- levo
- nitre azoles
- morpholine nitre
- dosage form
- morpholine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 208000015181 infectious disease Diseases 0.000 title claims abstract description 27
- 239000003814 drug Substances 0.000 title claims abstract description 16
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- 230000002141 anti-parasite Effects 0.000 title description 3
- 239000003096 antiparasitic agent Substances 0.000 title description 3
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 title 1
- 229960000282 metronidazole Drugs 0.000 title 1
- 238000002360 preparation method Methods 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 40
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Abstract
本发明提供左旋吗啉硝唑〔R－(－)－1－(2－甲基－5－硝基咪唑－1－基)－3－吗啉基丙烷－2－醇〕或其药用盐在制备抗寄生虫感染药物方面的用途，尤其是在制备抗阿米巴虫感染和抗阴道毛滴虫感染药物方面的用途。
Description
技术领域
本发明涉及左旋吗啉硝唑〔R-(-)-1-(2-甲基-5-硝基咪唑-1-基)-3-吗啉基丙烷-2-醇〕或其药用盐的新的用途，即在制备抗寄生虫感染药物中的用途。
背景技术
左旋吗啉硝唑为R-(-)-1-(2-甲基-5-硝基咪唑-1-基)-3-吗啉基丙烷-2-醇。2-甲基-5-硝唑咪唑类衍生物具有很好的抗厌氧菌活性，且制备方法已多有公开。公开号为CN1605586A的中国专利申请公开了α-取代的2-甲基-5-硝基咪唑-1-乙醇衍生物及其制备方法和用途，但对于α-取代的2-甲基-5-硝基咪唑-1-乙醇衍生物的光学活性未有说明。左旋吗啉硝唑目前未见有其相关报导。
发明内容
本发明的目的是提供左旋吗啉硝唑〔R-(-)-1-(2-甲基-5-硝基咪唑-1-基)-3-吗啉基丙烷-2-醇〕或其药用盐的新的用途。
本发明提供了左旋吗啉硝唑〔R-(-)-1-(2-甲基-5-硝基咪唑-1-基)-3-吗啉基丙烷-2-醇〕或其药用盐在制备抗寄生虫感染的药物中的用途。
按照本发明，左旋吗啉硝唑〔R-(-)-1-(2-甲基-5-硝基咪唑-1-基)-3-吗啉基丙烷-2-醇〕或其药用盐尤其用于制备抗阿米巴虫感染和抗阴道毛滴虫感染的药物。
按照本发明，所述抗寄生虫感染的药物可以为口服给药、静脉给药或阴道给药剂型。
按照本发明的一个实施方案，本发明的所述抗寄生虫感染的药物是口服给药剂型。优选地，所述口服给药剂型为片剂、胶囊剂或颗粒剂。所述口服给药剂型的给药剂量为10～40mg/kg/天，优选为20～30mg/kg/天。
按照本发明的另一个实施方案，本发明的所述抗寄生虫感染的药物是静脉给药剂型。优选地，所述静脉给药剂型为大容量输注制剂、小容量输注制剂或注射用冻干粉针剂。所述静脉给药剂型的给药剂量为5～40mg/kg/天，优选为10～20mg/kg/天。
按照本发明的另一个实施方案，本发明的所述抗寄生虫感染的药物是阴道给药剂型。优选地，所述阴道给药剂型为阴道栓剂、阴道凝胶剂或阴道泡腾片剂。所述阴道给药剂型的给药剂量为10～40mg/kg/天，优选为20～30mg/kg/天。
如实验所证实，左旋吗啉硝唑相较于右旋吗啉硝唑及消旋吗啉硝唑在体外具有明显更好的抗毛滴虫和溶组织阿米巴的作用，即左旋吗啉硝唑在抗寄生虫感染方面有明显更好的效果。左旋吗啉硝唑或其药用盐可以用于制备抗寄生虫感染的药物，特别是抗阿米巴虫感染和抗阴道毛滴虫感染的药物。
在本申请中，左旋吗啉硝唑的药用盐指的是左旋吗啉硝唑与无机或有机酸的盐，所述无机酸如盐酸、磷酸等，有机酸如酒石酸、甲磺酸等，其对活生物体是非毒性的。
在本发明中，抗寄生虫感染的口服给药制剂包含主药左旋吗啉硝唑〔R-(-)-1-(2-甲基-5-硝基咪唑-1-基)-3-吗啉基丙烷-2-醇〕或其药用盐和辅料，辅料选自崩解剂、粘合剂、润滑剂、填充剂中的一种或几种混合。
根据本发明口服给药制剂的辅料可为崩解剂、粘合剂、润滑剂、填充剂中任意组合。其中填充剂可以为预胶化淀粉、淀粉、糊精、蔗糖、乳糖、葡萄糖、甘露醇、微晶纤维素、硫酸钙、碳酸钙、轻质氧化镁中的一种或几种混合，优选淀粉；润滑剂为硬脂酸、硬脂酸钙、硬脂酸镁、滑石粉、氢化植物油、聚乙二醇4000或6000或8000、十二烷基硫酸钠、十二烷基硫酸镁中一种或几种混合，优选硬脂酸镁；崩解剂为交联羧甲基纤维素钠、交联聚维酮、淀粉、羧甲基淀粉钠、羟丙基淀粉、低取代羟丙基纤维素、聚山梨酯80、十二烷基硫酸钠中一种或几种混合，优选交联羧甲基纤维素钠；粘合剂优选为羟丙基纤维素、聚维酮、淀粉浆、糊精、蔗糖、糖浆、10-20％的明胶溶液、10％-25％的阿拉伯胶溶液、纤维素及其衍生物的一种或几种混合，优选聚维酮。
主药左旋吗啉硝唑或其药用盐的用量优选为20-100％，更优选为25-50％。崩解剂用量优选为0.01％-20％。润滑剂用量优选为0.1％-5.0％，余量为填充剂，粘合剂用量视具体生产中颗粒的流动性以及崩解情况而定。
具体制备方法如下：
将主药和辅料混合均匀后可直接压片或充填胶囊；或将主药用粘合剂制软材，制粒，干燥，整粒，直接包装成颗粒剂；或将主药用粘合剂制软材，制粒，干燥，整粒，或加入崩解剂、润滑剂混匀后，压制成片或充填入胶囊。其中片剂可包衣或不包衣，包衣材料可以为胃溶型包衣材料，也可以是肠溶型包衣材料。其中崩解剂可外加、内加或内外加。
在本发明中，抗寄生虫感染的静脉给药制剂含有左旋吗啉硝唑〔R-(-)-1-(2-甲基-5-硝基咪唑-1-基)-3-吗啉基丙烷-2-醇〕或其药用盐作为主药，加入不同的辅料可制为不同剂型的静脉给药制剂。
1.左旋吗啉硝唑或其药用盐大容量注射剂。加入辅料为渗透压调节剂时可制为输液制剂，优选渗透压调节剂为氯化钠、葡萄糖、葡萄糖酸钾、葡萄糖酸钠、葡萄糖酸钙、葡萄糖酸亚铁、葡萄糖酸镁、羧乙基淀粉、低分子右旋糖酐、甘油、碳酸氢钠、磷酸氢钾、硫酸镁、氯化钙、氯化钾、乳酸钠、木糖醇、山梨酸、麦芽糖、果糖的一种或几种的任意配比组合，更优选为氯化钠、葡萄糖的一种或几种的任意配比组合。其中所述等渗调节剂的浓度可根据稀溶液的依数性原理计算得到，也可以通过冰点降低数据法获得，并可根据人体的耐受程度将其用量范围扩大到0.5～3个等渗度，但优选与血浆等渗的浓度。
2.左旋吗啉硝唑或其药用盐小容量注射剂。由于左旋吗啉硝唑或其药用盐调节适宜的pH值就可以溶解于注射用水中，因此可不加辅料直接溶解左旋吗啉硝唑或其药用盐制为制剂或可以加有机溶媒为辅料来增加制剂的稳定性。可供选择的有机溶媒有丙二醇、甘油、乙醇、聚乙二醇200、聚乙二醇300、聚乙二醇400或聚乙二醇600，优选为丙二醇，有机溶媒浓度为1％-50％(ml/ml)。左旋吗啉硝唑或其药用盐用量与注射剂重量体积比为1-25(mg/ml)。
3.左旋吗啉硝唑或其药用盐注射用冻干粉针剂。左旋吗啉硝唑或其药用盐的注射用无菌粉针制剂包括注射用无菌粉末和注射用冻干粉针剂，其中左旋吗啉硝唑或其药用盐注射用无菌粉末采用溶媒结晶法制得或冷冻干燥粉碎后制得，故不需加辅料；左旋吗啉硝唑或其药用盐注射用冻干粉针剂中所加辅料为赋形剂，赋形剂可以为为甘露醇、山梨醇、右旋糖酐、乳糖、氯化钠、聚维酮中的一种或几种的混合物，优选甘露醇。左旋吗啉硝唑或其药用盐用量占总重的5％-50％，优选10％-30％，更优选20％；赋形剂用量占总重的50％-95％，优选为70％-90％，更优选为80％。
具体制备方法：
a.称取左旋吗啉硝唑或其药用盐和辅料(根据静脉给药剂型加入所需辅料)，加入部分注射用水，搅拌溶解或混悬；
b.采用溶媒结晶或冷冻干燥粉碎后制得左旋吗啉硝唑或其药用盐无菌粉末。或用可供静脉输注的酸调pH至3.0～8.0，优选为4.0～7.0，加注射用水至所需量，加入针用活性炭搅匀，钛棒脱炭，再经微孔滤精滤至澄明；经无菌过滤后冷冻干燥，得左旋吗啉硝唑或其药用盐的冻干粉针剂；或直接灌封于安瓿瓶或输液瓶或软袋中，湿热灭菌，即得左旋吗啉硝唑或其药用盐的小容量或大容量注射剂。
其中可供静脉输注的酸可以为盐酸、乳酸、甲磺酸、硫酸、醋酸、酒石酸、氨基酸、磷酸或其药用盐、枸橼酸或其药用盐，优选盐酸和乳酸。
按照本发明的另一个实施方案，本发明的所述抗寄生虫感染的药物是阴道给药剂型。优选地，所述阴道给药剂型为阴道栓剂、阴道凝胶剂或阴道泡腾片剂。
(1)左旋吗啉硝唑或其药用盐阴道泡腾片剂：
成份：主药左旋吗啉硝唑或其药用盐和药用辅料，所述药用辅料主要包括赋形剂、酸或酸式盐组成的酸系统、碳酸盐组成的碱系统、粘合剂、润滑剂、助流剂，根据需要还可加入崩解剂、起泡剂。
制备方法：采用粉末直接压片工艺或湿法制粒工艺。粉末直接压片工艺主要包括以下步骤：将原辅料分别粉碎过筛后，混合均匀，压制成每片主药量含为10％-80％的圆形片或异形片。湿法制粒工艺主要包括以下步骤：原辅料分别粉碎过筛后，全部或部分主药、全部或部分赋形剂、酸或酸式盐组成的酸系统，用适量的粘合剂制成颗粒A，全部或部分主药、全部或部分赋形剂、碳酸盐组成的碱系统，用适量的粘合剂制成颗粒B，将颗粒A和颗粒B分别干燥后，再加入润滑剂或助流剂混合均匀，压制成每片含主药量为10％-80％的圆形片或异形片。
上述左旋吗啉硝唑或其药用盐优选为30％-70％，更优选50％。
其中赋形剂选自淀粉、预胶化淀粉、乳糖、微晶纤维素、糊精、葡萄糖、甘露醇中的一种或几种，优选淀粉、预胶化淀粉、微晶纤维素，更优选淀粉，用量占片重的5％-75％，优选10％-40％，更优选20～30％。
上述酸系统中的酸包括枸橼酸、酒石酸、琥珀酸、富马酸、己二酸、苹果酸、水溶性氨基酸，酸式盐包括酒石酸氢钾、酒石酸氢钠、枸橼酸二氢钾、枸橼酸二氢钠、富马酸钠、或矿酸，如硼酸中的一种或几种，优选酒石酸；碱系统中碳酸盐包括碳酸氢钠、碳酸钠、碳酸氢钾、碳酸钾、碳酸氢钙或碳酸钙中一种或几种，优选碳酸氢钠；酸、碱系统的用量分别占片重的5％-60％，优选10％-30％，更优选为15％～25％。
粘合剂可以为淀粉浆、聚乙烯吡咯烷酮溶液、羟丙甲纤维素溶液、糊精浆、糖浆、胶浆、纤维素及其衍生物中的一种或几种，优选5～20％聚乙烯吡咯烷酮无水乙醇溶液，用量视实际操作定。
润滑剂或助流剂可以为硬脂酸、硬脂酸镁、硬脂酸钙、滑石粉、氢化植物油、聚乙二醇4000及6000、十二烷基硫酸镁、十二烷基硫酸钠、微粉硅胶中的一种或几种，优选硬脂酸镁。用量占片重的0.01％-3％。
崩解剂可以为交联羧甲基纤维素钠、交联聚维酮、淀粉及其衍生物、低取代羟丙基纤维素、表面活性剂中的一种或几种，优选羧甲基纤维素钠。用量占片重的0.01％-10％。
起泡剂为为十二烷基硫酸钠、聚山梨酯20-80等具有较强的亲水性和较高的HLB值的表面活性剂中的一种或几种，优选十二烷基硫酸钠。用量占片重的0.01％-2％。
(2)左旋吗啉硝唑或其药用盐阴道栓剂：
成分：主药左旋吗啉硝唑或其药用盐及辅料栓剂基质。
制备方法：将主药过筛，栓剂基质加热融化，加入主药并搅拌均匀，保温灌模。
其中主药左旋吗啉硝唑或其药用盐含量为10％-50％，更优选为30％。
其中辅料栓剂基质选自可可豆脂、半合成或全合成脂肪酸甘油酯、甘油明胶、聚乙二醇类、聚氧乙烯(40)单硬脂酸类、泊洛沙姆，优选半合成脂肪酸甘油酯；用量占每剂重量的50％-90％，更优选为70％。
(3)左旋吗啉硝唑或其药用盐阴道凝胶剂：
成分：主药左旋吗啉硝唑或其药用盐及辅料凝胶基质，凝胶基质可以为水性凝胶基质或油性凝胶基质，并加入透皮促进剂、防腐剂、pH调节剂。
制备方法：将主药直接加入或用药用溶媒溶解后加入到凝胶基质中，搅拌均匀即得。
其中药用溶媒为乙醇、丙二醇、甘油、聚乙二醇或水，优选丙二醇。
其中主药左旋吗啉硝唑或其药用盐含量为0.25％-10％。
水溶性凝胶基质用量为70％-99.7％，为增稠剂加水溶胀而成，其中增稠剂可以选白西黄耆胶、卡波普、明胶、淀粉及纤维素衍生物、聚羧乙烯、海藻酸钠中的一种或几种，优选卡波普，用量占基质总重0.1％-20％。
油性凝胶基质可以选自液体石蜡与聚氧乙烯或脂肪油与胶体硅或铝皂、锌皂，用量为80％-99.7％。
透皮促进剂选白月桂氮卓酮、油酸、薄荷油、丙二醇中的一种或几种，优选月桂氮卓酮，用量为0.1％-20％。
防腐剂选自尼泊金类、苯甲酸与苯甲酸钠、山梨酸或其药用盐类、苯扎溴铵、醋酸氯乙定、邻苯基苯酚、苯甲醇、三氯叔丁醇中的一种或几种，优选苯扎溴铵，用量为0.001％-5％。
pH调节剂选自氢氧化钠、氢氧化钾、氢氧化铝、三乙醇胺、盐酸、枸橼酸、冰醋酸中的一种或几种，优选氢氧化钠，调节基质pH值至5-9。
具体实施方式
实施例1.制备左旋吗啉硝唑片剂
处方组成：
左旋吗啉硝唑 100mg/片
预胶化淀粉 100mg/片
微晶纤维素 40mg/片
淀粉 50mg/片
羧甲基淀粉钠 5mg/片
硬脂酸镁 5mg/片
聚维酮水溶液(6％) 适量
制备工艺：以制成1000片左旋吗啉硝唑片剂为例，具体制备方法是先将主药和辅料分别过100目筛，称取处方量的左旋吗啉硝唑、预胶化淀粉、微晶纤维素、淀粉、羧甲基淀粉钠混合均匀，用6％聚维酮水溶液制软材，20目筛制湿颗粒，于40℃烘干，用18目筛整粒，向颗粒中加入处方量的硬脂酸镁，混合均匀，压片，或用8％的欧巴代95％乙醇溶液包衣至片芯增重2～3％，即得本品的薄膜衣片。
实施例2.制备左旋吗啉硝唑胶囊制剂
处方组成：
左旋吗啉硝唑盐酸盐 300mg/片
淀粉 45mg/片
硬脂酸镁 5mg/片
6％的淀粉浆 适量
制备工艺：将原辅料分别过100目筛。称取处方量的左旋吗啉硝唑盐酸盐，淀粉，混合均匀，用6％淀粉浆制软材，22目筛制粒，于40℃烘干，用20目整粒。加入处方量的硬脂酸镁，混合均匀后，将颗粒充填于1号胶囊中，每粒约350mg。
实施例3.制备左旋吗啉硝唑颗粒制剂
处方组成：
左旋吗啉硝唑 300mg/袋
蔗糖 400mg/袋
微晶纤维素 150mg/袋
淀粉 150mg/袋
6％的淀粉浆 适量
制备工艺：将原辅料分别过100目筛。称取处方量的左旋吗啉硝唑、蔗糖、微晶纤维素、淀粉，混合均匀，用6％淀粉浆制软材，16目筛制粒，于40℃烘干，用14目整粒。用40目筛筛去细粉，按每袋1g分装。
实施例4.制备左旋吗啉硝唑阴道泡腾片剂
处方组成：
左旋吗啉硝唑 100g
碳酸氢钠 145g
十二烷基硫酸钠 1.6g
微晶纤维素 180g
低取代羟丙基纤维素 45g
酒石酸 140g
硬脂酸镁 10g
制备工艺：将左旋吗啉硝唑过100目筛，其余各辅料分别过80目筛，称取处方量的左旋吗啉硝唑，碳酸氢钠，十二烷基硫酸钠，微晶纤维素，低取代羟丙基纤维素，酒石酸硬脂酸镁，混合均匀，压片。片重620mg/片。
实施例5.制备左旋吗啉硝唑阴道栓剂
处方组成：
左旋吗啉硝唑 100g
聚乙二醇-4000 1200g
制备工艺：称取处方量的聚乙二醇-4000于60℃的水浴中加热溶解后，加入处方量的左旋吗啉硝唑，搅拌均匀，趁热灌装于栓剂模具中，放冷，待基质凝固后，取出，即得所要栓剂。
实施例6.制备左旋吗啉硝唑输液制剂
处方组成：
左旋吗啉硝唑 300g
氯化钠 900g
注射用水加至 100L
制备工艺：称取处方量的左旋吗啉硝唑，渗透压调节剂加到80％约40℃的注射用水中，搅拌使溶解，用1mol/LNaOH调节pH至6.0左右，补加注射用水至全量，加入0.05％(w/v)的针用活性炭，搅拌20min，溶液用钛棒循环脱碳，测定中间体含量及pH值，合格后，药液经0.22um微孔滤膜后灌封于100ml的输液瓶中，然后在115℃热压灭菌30min，冷却即得成品。
实施例7.制备左旋吗啉硝唑冻干制剂
处方组成：
左旋吗啉硝唑 300g
甘露醇 100g
注射用水加至 2L
制备工艺：称取处方量的左旋吗啉硝唑，甘露醇加到80％约40℃的注射用水中，搅拌使溶解，用1mol/LNaOH调节pH至6.0左右，补加注射用水至全量，加入0.05％(w/v)的针用活性炭，搅拌20min，溶液用钛棒循环脱碳，测定中间体含量及pH值，合格后，药液经0.22um微孔滤膜后灌封于2ml的西林瓶，冷冻干燥至水分小于2.0％，压盖，包装即得成品。
实施例8.制备左旋吗啉硝唑注射液制剂
处方组成：
左旋吗啉硝唑 300g
注射用水加至 2L
制备工艺：称取处方量的左旋吗啉硝唑加到80％约40℃的注射用水中，搅拌使溶解，用1mol/LNaOH调节pH至6.0左右，补加注射用水至全量，加入0.05％(w/v)的针用活性炭，搅拌20min，溶液用钛棒循环脱碳，测定中间体含量及pH值，合格后，药液经0.22um微孔滤膜后灌封于2ml的安瓿瓶中，然后在115℃热压灭菌30min，冷却即得成品。
实施例9.制备左旋吗啉硝唑凝胶剂
处方组成：
左旋吗啉硝唑 100g
卡波普 100g
氢氧化钠 40g
蒸馏水 10000g
制备工艺：称取处方量的卡波普浸泡于3000g的蒸馏水中，使其完全溶胀。将处方量的NaOH溶解于2000g的蒸馏水中，并将其倒入溶胀后的卡波普中，搅拌均匀。将左旋吗啉硝唑溶解于5000g的蒸馏水中，并将此溶液与上述溶液混合，完全搅拌均匀后，将其灌入铝管中，每支约10g。
实施例10.左旋吗啉硝唑抗毛滴虫感染和抗溶组织阿米巴虫感染的药效
对左旋吗啉硝唑、右旋吗啉硝唑及消旋吗啉硝唑进行抗毛滴虫感染及抗溶组织阿米巴虫感染体外药效比较。取左旋吗啉硝唑、右旋吗啉硝唑及消旋吗啉硝唑用培养液稀释到4、40、400ug/ml三种浓度，分别加入至培养管内，向管内加入虫体，当含药或对照培养管内的虫于36±0.5℃培养48小时后，从培养管近底部吸取培养液滴于载玻片上，复上盖玻片镜检，发现虫体者为阳性，并做相对性定量比较，未发现虫体者为阴性。为避免漏检，将阴性培养物再作不加药的正常传代培养，48小时后再观察，做出结果判断。
结果见下表。
| 药物 | 浓度(ug/ml) | 溶组织阿米巴 | 阴道毛滴虫 | ||
| 培养 | 转接种培养 | 培养 | 转接种培养 | ||
| 左旋吗啉硝唑 | 4 | + | * | + | * |
| 40 | - | - | - | - | |
| 400 | - | - | - | - | |
| 右旋吗啉硝唑 | 4 | ++ | * | ++ | * |
| 40 | + | * | - | - | |
| 400 | - | - | |||
| 消旋吗啉硝唑 | 4 | ++ | * | ++ | * |
| 40 | - | - | - | - | |
| 400 | - | - | |||
| 空白对 | - | ++++ | * | ++++ | * |
注：+示每高倍镜滴虫数为1-20个；++为21-50个；+++为51-100个；+++为＞100个。
*未作转接种培养
临床分离的人毛滴虫在4ug/ml的左旋吗啉硝唑中经48小时，即呈现一定的抑制。与空白对照组相比，虫数减少，活动较慢，部分虫体变圆，并含大量颗粒或结构模糊，不活动。40ug/ml时未见活动的虫体，个别视野内可见数个圆形、结构模糊或呈颗粒变性的虫体，经转种培养48小时也未见有活动的虫体，说明此浓度下全部虫体均被左旋吗啉硝唑杀死。空白对照组的虫体生长增殖良好，虫体呈梨形，活动正常。
溶组织阿米巴虫在4ug/ml浓度的左旋吗啉硝唑溶液中培养48小时后，虫数均明显减少，有些虫体变小，缩为圆形，伪足运动不明显，个别虫体呈现混浊濒临死亡。在40ug/ml浓度培样48小时，未见活动虫体，个别视野内见有2-3个缩成圆形且较小的虫体，结构模糊或呈颗粒变性，初步判定为死亡，转接种48小时后也未见活动的或死亡的虫体，表明虫体全部死亡。400ug/ml浓度的左旋吗啉硝唑培养液中培养48小时，虫体也全部死亡。
本实验重复两次，结果相同，显示左旋吗啉硝唑相较于右旋吗啉硝唑及消旋吗啉硝唑在体外具有明显更好的抗毛滴虫和溶组织阿米巴的作用，即左旋吗啉硝唑在抗寄生虫感染方面有明显更好的效果。
Claims (9)
1.左旋吗啉硝唑〔R-(-)-1-(2-甲基-5-硝基咪唑-1-基)-3-吗啉基丙烷-2-醇〕或其药用盐在制备抗寄生虫感染的药物中的用途。
2.根据权利要求1所述的用途，其中所述抗寄生虫感染为抗阿米巴虫感染和抗阴道毛滴虫感染。
3.根据权利要求1所述的用途，其中所述药物为口服给药、静脉给药或阴道给药剂型。
4.根据权利要求3所述的用途，其中所述口服给药剂型为片剂、胶囊剂或颗粒剂。
5.根据权利要求4所述的用途，其中所述口服给药剂型的给药剂量为10～40mg/kg/天，优选为20～30mg/kg/天。
6.根据权利要求3所述的用途，其中所述静脉给药剂型为大容量输注制剂、小容量输注制剂或注射用冻干粉针剂。
7.根据权利要求6所述的用途，其中所述静脉给药剂型的给药剂量为5～40mg/kg/天，优选为10～20mg/kg/天。
8.根据权利要求3所述的用途，其中所述阴道给药剂型为阴道栓剂、阴道凝胶剂或阴道泡腾片剂。
9.根据权利要求8所述的用途，其中所述阴道给药剂型的给药剂量为10～40mg/kg/天，优选为20～30mg/kg/天。
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007079653A1 (en) * | 2006-01-06 | 2007-07-19 | Jiangsu Hansen Pharmaceutical Co., Ltd. | OPTICALLY PURE α-SUBSTITUTED 2-METHYL-5-NITROIMIDAZOLE-1-ETHANOL DERIVATIVES |
| CN106674124A (zh) * | 2015-11-09 | 2017-05-17 | 陕西合成药业股份有限公司 | 一种盐酸左旋吗啉硝唑晶型及其制备方法和用途 |
| CN111973569A (zh) * | 2019-05-21 | 2020-11-24 | 江苏豪森药业集团有限公司 | 含有硝基咪唑类衍生物的药物组合物及其制备方法 |
| CN112137955A (zh) * | 2020-11-05 | 2020-12-29 | 江苏豪森药业集团有限公司 | 一种吗啉硝唑注射液及其制备方法 |
| CN114907250A (zh) * | 2021-02-06 | 2022-08-16 | 华创合成制药股份有限公司 | 一种氘代吗啉硝唑及其用途 |
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| JP3538370B2 (ja) * | 1999-07-21 | 2004-06-14 | 株式会社昭栄 | 皮膚の色素異常症、瘢痕等の治療用又は予防用外用剤 |
| CN100344626C (zh) * | 2003-10-08 | 2007-10-24 | 连云港恒邦医药科技有限公司 | α－(吗啉－1－基)甲基－2－甲基－5－硝基咪唑－1－乙醇用于制备抗厌氧菌药物的用途 |
| CN1305469C (zh) * | 2005-07-08 | 2007-03-21 | 南京圣和药业有限公司 | 左旋奥硝唑在制备抗寄生虫感染的药物中的应用 |
| CN1789250A (zh) * | 2005-12-16 | 2006-06-21 | 西安新安医药科技有限公司 | 一组硝基咪唑类衍生物的光学对映体、制备方法及其用途 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007079653A1 (en) * | 2006-01-06 | 2007-07-19 | Jiangsu Hansen Pharmaceutical Co., Ltd. | OPTICALLY PURE α-SUBSTITUTED 2-METHYL-5-NITROIMIDAZOLE-1-ETHANOL DERIVATIVES |
| CN106674124A (zh) * | 2015-11-09 | 2017-05-17 | 陕西合成药业股份有限公司 | 一种盐酸左旋吗啉硝唑晶型及其制备方法和用途 |
| CN111973569A (zh) * | 2019-05-21 | 2020-11-24 | 江苏豪森药业集团有限公司 | 含有硝基咪唑类衍生物的药物组合物及其制备方法 |
| CN112137955A (zh) * | 2020-11-05 | 2020-12-29 | 江苏豪森药业集团有限公司 | 一种吗啉硝唑注射液及其制备方法 |
| CN114907250A (zh) * | 2021-02-06 | 2022-08-16 | 华创合成制药股份有限公司 | 一种氘代吗啉硝唑及其用途 |
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