CN1305469C - 左旋奥硝唑在制备抗寄生虫感染的药物中的应用 - Google Patents
左旋奥硝唑在制备抗寄生虫感染的药物中的应用 Download PDFInfo
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Abstract
本发明提供了左旋奥硝唑在制备抗寄生虫感染的药物中的应用。试验证明左旋奥硝唑在治疗寄生虫感染(特别是阴道毛滴虫感染和盲肠阿米巴虫感染)的治疗作用方面要优于右旋奥硝唑和消旋奥硝唑,因此将左旋奥硝唑制成抗寄生虫感染药物更具有实用性。本发明还特别涉及将左旋奥硝唑制成适合临床使用的剂型,包括口服制剂、静脉给药制剂及阴道给药制剂。
Description
技术领域
本发明涉及左旋奥硝唑在制备抗寄生虫感染的药物中的应用,特别涉及将左旋奥硝唑制成适合临床使用的剂型并用于抗寄生虫感染,特别是阴道毛滴虫感染和盲肠阿米巴虫感染,所述剂型优选包括口服制剂、静脉给药制剂及阴道给药制剂。
背景技术
左旋奥硝唑(1-(3-氯-2-S-(-)羟丙基)-2-甲基-5-硝基咪唑)为奥硝唑(Ornidazole,CAS 16773-42-5)的左旋体,奥硝唑为硝基咪唑类衍生物,是一种强力抗厌氧菌及抗原虫感染的药物,也是继甲硝唑后新研制成的疗效更高、疗程更短、耐受性更好、体内分布更广的第三代硝基咪唑类衍生物。奥硝唑的抗微生物作用是通过其分子中的硝基在无氧环境中还原成氨基,或通过自由基的形成与细胞成分相互作用,从而导致微生物的死亡。市售奥硝唑制剂均以奥硝唑消旋体为主药。中国有从奥硝唑消旋体通过酶法拆分得左、右旋奥硝唑(见CN 1400312A)的专利申请,但未对左、右旋奥硝唑及消旋奥硝唑进行药理药效比较研究,也从未公开它们的药效活性之间的区别。
发明内容
临床使用表明奥硝唑具有很好的治疗厌氧菌感染的效果,但也存在一些不良反应。本发明人通过对奥硝唑的左旋体进行药代动力学、药效学、毒理学、一般药理学等试验研究,发现左旋奥硝唑药代动力学特性优于右旋奥硝唑和消旋奥硝唑,且中枢毒性低于右旋奥硝唑和消旋奥硝唑。
急性毒理研究显示小鼠静脉注射左旋奥硝唑的LD50值为332mg/kg(95%可信限为312~362mg/kg),小鼠腹腔注射左旋奥硝唑的LD50值为1378mg/kg(95%可信限为1244~1526mg/kg),小鼠灌胃给药左旋奥硝唑的LD50值为1069mg/kg(95%可信限为935.3~1222mg/kg)。小鼠静脉注射消旋奥硝唑的LD50值为306mg/kg(95%可信限为272~346mg/kg),小鼠腹腔注射消旋奥硝唑的LD50值为1115mg/kg(95%可信限为1026~1212mg/kg),小鼠灌胃给药消旋奥硝唑的LD50值为769.4mg/kg(95%可信限为674.2~878.0mg/kg )。由此可见,左旋奥硝唑毒性作用比消旋奥硝唑更低,安全性相对要高。
将左旋奥硝唑组、右旋奥硝唑组和消旋奥硝唑组分别静脉给药2周对非啮齿类动物Beagle犬的毒性试验表明左旋奥硝唑与右旋奥硝唑及消旋奥硝唑相比中枢毒性更低,用药更加安全。
在一般药理作用试验中考察了左旋奥硝唑、右旋奥硝唑及消旋奥硝唑对小鼠中枢神经系统的影响。试验结果表明,左旋奥硝唑对中枢神经的抑制作用与右旋奥硝唑和消旋奥硝唑相比明显降低。
基于上述实验,发明人对左旋奥硝唑在治疗寄生虫感染(包括小鼠阴道毛滴虫感染和小鼠盲肠阿米巴虫感染)的治疗作用方面进行了药效学研究,发现左旋奥硝唑在治疗寄生虫感染(包括小鼠阴道毛滴虫感染和小鼠盲肠阿米巴虫感染)的治疗作用方面要优于右旋奥硝唑和消旋奥硝唑。具体实验如下:
(一)对阴道毛滴虫引起感染的药效学研究
雄性ICR小鼠,分别腹腔注射含3×106阴道毛滴虫的液体0.4ml(阴道毛滴虫取自临床患者),将小鼠随机分为19组,每组10只,其中溶媒对照组经尾静脉注射空白溶液,给药组分别于感染后2、24、48、72小时静脉注射给药。于感染5天后处死动物,冲洗内脏,冲洗液经离心后镜检有无活动虫体。进行解剖检查,观察各组内脏和腹腔是否出现脓肿,显微镜下检查肿内的活滴虫数。结果为溶媒对照组小鼠腹腔和内脏均形成多发性小脓肿,给药组小鼠脓肿被抑制,活滴虫数减少。计算50%和90%阿米巴虫被抑制的药物剂量即ED50和ED90。结果见表1。
表1.对阴道毛滴虫引起感染的药效学研究
药物 | ED50 | 95%可信限 | ED90 | 95%可信限 |
左旋奥硝唑右旋奥硝唑消旋奥硝唑 | 9.114.111.3 | 4.8~17.48.3~24.05.5~22.9 | 32.654.543.8 | 17.0~61.732.4~93.321.4~89.1 |
上述实验结果表明,左旋奥硝唑在治疗小鼠阴道毛滴虫感染的治疗作用方面要优于右旋奥硝唑和消旋奥硝唑。
(二)对盲肠阿米巴虫引起的感染的药效研究
雄性ICR小鼠,在盲肠上注射0.2ml含约20万单位的痢疾阿米巴虫液体,将小鼠随机分为19组,每组10只,其中溶媒对照组经尾静脉注射空白溶液,给药组分别于感染后24、48、72小时静脉注射给药。于感染6天后处死动物,取盲肠黏膜切片在显微镜下做阿米巴虫的阶段对比性研究。结果为溶媒对照组小鼠的盲肠上有痢疾阿米巴虫生长,而给药组小鼠可以清除阿米巴虫。计算50%和90%阿米巴虫被抑制的药物剂量,即ED50和ED90,结果见表2。
表2.对盲肠阿米巴虫引起的感染的药效学研究
药物 | ED50 | 95%可信限 | ED90 | 95%可信限 |
左旋奥硝唑右旋奥硝唑消旋奥硝唑 | 10.513.311.4 | 5.4~20.48.3~20.85.6~22.9 | 41.264.455.2 | 21.4~81.340.7~102.327.5~109.6 |
上述实验结果表明,左旋奥硝唑在治疗小鼠盲肠阿米巴虫感染的治疗作用方面略优于右旋奥硝唑和消旋奥硝唑。
通过上述实验表明左旋奥硝唑在治疗寄生虫感染(包括小鼠阴道毛滴虫感染和小鼠盲肠阿米巴虫感染)的治疗作用方面要略优于右旋奥硝唑和消旋奥硝唑,而左旋奥硝唑药代动力学特性优于右旋奥硝唑和消旋奥硝唑,且中枢毒性低于右旋奥硝唑和消旋奥硝唑,故将左旋奥硝唑制为抗寄生虫感染药物更具有实用性。
本发明还提供了含左旋奥硝唑为主药的药物制剂,优选所述制剂为口服制剂、静脉给药制剂或阴道给药制剂。所述口服制剂给药剂量优选为10~40mg/kg/天,更优选为20~30mg/kg/天。所述静脉给药制剂给药剂量优选为5~40mg/kg/天,更优选为10~20mg/kg/天。所述阴道给药制剂给药剂量优选为10~40mg/kg/天,更优选为20~30mg/kg/天
具体实施方式。
实施例1:
处方组成为:
(a)左旋奥硝唑 250mg/片
(b)预胶化淀粉 80mg/片
(c)羧甲基淀粉钠 4mg/片
(d)硬脂酸镁 3mg/片
以制成1000片左旋奥硝唑片剂为例,具体制备方法是:先将原辅料过100目筛,称取处方量的左旋奥硝唑和预胶化淀粉混合均匀,加8%淀粉浆制软材,制粒,烘干,整粒,向颗粒中加入处方量羧甲基淀粉钠和硬脂酸镁,压片,用8%的欧巴代95%乙醇溶液包衣。
实施例2:
处方组成:
(a)左旋奥硝唑 250mg/粒
(b)淀粉 45mg/粒
(c)硬脂酸镁 2mg/粒
以制备1000粒左旋奥硝唑胶囊剂为例。具体制备方法是先将原辅料过100目筛,称取处方量的左旋奥硝唑和淀粉混合均匀,加6%淀粉浆制软材,制粒,烘干,整粒,向颗粒中加入处方量硬脂酸镁混合均匀,充填胶囊。
实施例3:
处方组成:
(a)左旋奥硝唑 250mg/袋
(b)甘露醇 250mg/袋
(c)蔗糖 200mg/袋
(d)羧甲基淀粉钠 20mg/袋
以制备1000袋左旋奥硝唑颗粒剂为例。具体制备方法是先将原辅料过100目筛,称取处方量的左旋奥硝唑、甘露醇、糖粉和羧甲基淀粉钠混合均匀,加8%淀粉浆制软材,制粒,烘干,整粒,包装。
实施例4:
处方组成为:
(a)左旋奥硝唑 5mg/ml
(b)氯化钠 8.30mg/m1
(c)注射用水加至 100ml
以制成100瓶左旋奥硝唑氯化钠注射液制剂为例,具体制备方法是先称取处方量的左旋奥硝唑和氯化钠,加40℃注射用水8L,搅拌,溶解;用0.1mol/L盐酸调pH至4.0;加40℃注射用水至全量;向上述溶液中加入0.1%活性炭,搅拌,放置15min,5μm钛棒脱炭,再经筒式滤器0.45μm和0.22μm的微孔滤膜精滤;灌封于100ml玻璃输液瓶中,于100℃流动蒸汽灭菌45min。
实施例5:
处方组成:
(a):左旋奥硝唑 5mg/ml
(b):葡萄糖 50mg/ml
(c):注射用水加至 100ml
以制备100瓶左旋奥硝唑葡萄糖注射液为例。具体制备方法是称取处方量的左旋奥硝唑和葡萄糖溶于8L 45℃的注射用水中,用0.1mol/L的盐酸,调节pH至3.5。加45℃注射用水至全量。加0.15%活性炭,搅拌,放置15min,5μm钛棒脱炭,再经筒式滤器0.45μm和0.22μm的微孔滤膜精滤,灌封于100ml玻璃输液瓶中,于100℃流动蒸汽灭菌45min,即得左旋奥硝唑葡萄糖注射液。
实施例6:
处方组成:
(a)左旋奥硝唑 25mg/ml
(b)丙二醇 0.5ml/ml
(c)注射用水加至 10ml
以制备100瓶左旋奥硝唑注射液为例。具体制备方法是称取处方量的左旋奥硝唑,溶于处方量的约45℃的丙二醇中,加入100ml的45℃注射用水,搅匀;用0.1mo1/L的盐酸调pH至4.5,溶解后,加45℃注射用水至全量;加入0.1%针用活性炭,搅拌,放置15min,5μm钛棒脱炭,再经筒式滤器0.45μm和0.22μm的微孔滤膜精滤;灌封于安瓿瓶中,于100℃流动蒸汽灭菌45min,即得左旋奥硝唑注射液。
实施例7:
处方组成为:
(a)左旋奥硝唑 500mg/片
(b)碳酸氢钠 300mg/片
(c)低取代羟丙基纤维素 100mg/片
(d)十二烷基硫酸钠 3.2mg/片
(e)微晶纤维素 440mg/片
(f)酒石酸 280mg/片
(g)聚乙二醇 16mg/片
以制成100片左旋奥硝唑阴道泡腾片制品为例,具体制备方法是将处方中各原辅料分别研磨过80目筛;称取处方量左旋奥硝唑、十二烷基硫酸钠、碳酸氢钠及75%处方量微晶纤维素、80%处方量低取代羟丙基纤维素混合均匀后,用60%乙醇制软材,用14目尼龙筛制粒,将湿颗粒置于60℃烘箱中干燥,至水分<1.0%时,取出,用12目尼龙筛整粒,得颗粒A;称取处方量有机酸及剩余处方量微晶纤维素、低取代羟丙基纤维素,混合均匀后,用60%乙醇制软材,并用14目尼龙筛制粒,将湿颗粒放置于60℃烘箱中干燥,至水分≤1.5%,取出,用12目尼龙筛整粒,得颗粒B;将颗粒A和颗粒B及处方量聚乙二醇混合均匀;用异形冲头压片、包装,即得。
Claims (10)
1.左旋奥硝唑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,其特征在于将左旋奥硝唑制为适合临床使用的抗寄生虫感染的药物制剂,所述制剂包括口服制剂、静脉给药制剂及阴道给药制剂。
3.根据权利要求2所述的用途,其特征在于所述口服制剂给药剂量为10~40mg/kg/天。
4.根据权利要求3所述的用途,其特征在于所述口服制剂给药剂量为20~30mg/kg/天。
5.根据权利要求2所述的用途,其特征在于所述静脉给药制剂给药剂量为5~40mg/kg/天。
6.根据权利要求5所述的用途,其特征在于所述静脉给药制剂给药剂量为10~20mg/kg/天。
7.根据权利要求2所述的用途,其特征在于所述阴道给药制剂给药剂量为10~40mg/kg/天。
8.根据权利要求7所述的用途,其特征在于所述阴道给药制剂给药剂量为20~30mg/kg/天。
9.根据权利要求1-8任一项所述的用途,其特征在于所述寄生虫感染为阴道毛滴虫感染。
10.根据权利要求1-8任一项所述的用途,其特征在于所述寄生虫感染为盲肠阿米巴虫感染。
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CNB2005100835172A CN1305469C (zh) | 2005-07-08 | 2005-07-08 | 左旋奥硝唑在制备抗寄生虫感染的药物中的应用 |
PCT/CN2006/001204 WO2007006197A1 (fr) | 2005-07-08 | 2006-06-05 | Utilisation de lévo-ornidazole pour la préparation de médicaments contre les infections parasitaires |
EP06742090A EP1902712B1 (en) | 2005-07-08 | 2006-06-05 | Use of levo-ornidazole for preparing antiparasitic infection drug |
DE602006019250T DE602006019250D1 (de) | 2005-07-08 | 2006-06-05 | Verwendung von levo-ornidazol zur herstellung eines antiparasitären infektionswirkstoffs |
ES06742090T ES2358441T3 (es) | 2005-07-08 | 2006-06-05 | Uso de levo-omidazol para preparar fármaco anti-infecciones parasitarias. |
AT06742090T ATE493127T1 (de) | 2005-07-08 | 2006-06-05 | Verwendung von levo-ornidazol zur herstellung eines antiparasitären infektionswirkstoffs |
US11/909,623 US20080177083A1 (en) | 2005-07-08 | 2006-06-05 | Use of Levo-Ornidazole For Preparing Anti-Parasitic Infection Drug |
US13/831,706 US20130202698A1 (en) | 2005-07-08 | 2013-03-15 | L-ornidazole formulations and their applications in treatment of parasitic infections |
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CNB2005100835172A CN1305469C (zh) | 2005-07-08 | 2005-07-08 | 左旋奥硝唑在制备抗寄生虫感染的药物中的应用 |
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CN1305469C true CN1305469C (zh) | 2007-03-21 |
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US (1) | US20080177083A1 (zh) |
EP (1) | EP1902712B1 (zh) |
CN (1) | CN1305469C (zh) |
AT (1) | ATE493127T1 (zh) |
DE (1) | DE602006019250D1 (zh) |
ES (1) | ES2358441T3 (zh) |
WO (1) | WO2007006197A1 (zh) |
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CN100451023C (zh) * | 2006-01-06 | 2009-01-14 | 陕西新安医药科技有限公司 | 左旋奥硝唑磷酸酯及其制备方法和用途 |
CN1329379C (zh) * | 2006-01-06 | 2007-08-01 | 沈阳中海生物技术开发有限公司 | 抗厌氧菌化合物 |
CN100534429C (zh) * | 2006-05-12 | 2009-09-02 | 南京圣和药业有限公司 | 左旋奥硝唑阴道给药制剂及其制备方法和制药用途 |
CN100387233C (zh) * | 2006-06-09 | 2008-05-14 | 南京圣和药业有限公司 | 左旋吗啉硝唑在制备抗寄生虫感染药物中的用途 |
CN102813622B (zh) * | 2012-08-09 | 2013-06-26 | 西安万隆制药股份有限公司 | 一种奥硝唑氯化钠注射液组合物 |
WO2016100203A1 (en) * | 2014-12-20 | 2016-06-23 | Gregg John Malcolm Hall | Antimicrobial drug synthesis and therapeutic compositions |
WO2018039087A1 (en) * | 2016-08-20 | 2018-03-01 | Gregg John Malcolm Hall | Antimicrobial drug methods of use & therapeutic compositions |
CN114478392B (zh) * | 2020-10-26 | 2023-09-29 | 南京锐志生物医药有限公司 | 一种抗厌氧菌化合物的酯类前药、药物组合物及其制备方法和应用 |
CN114452315B (zh) * | 2022-03-16 | 2023-04-07 | 郑州大学第一附属医院 | 一种阴道泡腾栓及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3435049A (en) * | 1965-05-19 | 1969-03-25 | Hoffmann La Roche | Nitroimidazole derivatives |
CS18384A1 (en) * | 1984-01-09 | 1984-11-19 | Marian Ing Simko | Sposob pripravy 1 3 chlor 2 hydroxypropyl 2metyl 5 nitroimi dazolu |
WO1994015922A1 (en) * | 1992-07-31 | 1994-07-21 | Warner Lambert Company | Novel process for preparing chiral [[(2-bromoethyl)amino]methyl]-2-nitro-1h-imidazol-1-ethanol and related compounds |
CN1400312A (zh) * | 2002-08-23 | 2003-03-05 | 中国科学院上海有机化学研究所 | 外消旋奥硝唑的酶法拆分方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4289751A (en) * | 1979-06-29 | 1981-09-15 | Merck & Co., Inc. | Effervescent enteric-coated formulation of soluble form of erythromycin and therapeutic use thereof |
US6576250B1 (en) * | 1998-03-27 | 2003-06-10 | Cima Labs Inc. | Pharmaceutical compositions for rectal and vaginal administration |
CN1179951C (zh) * | 2002-07-19 | 2004-12-15 | 中国科学院上海有机化学研究所 | 噻克硝唑的光学对映体、制备方法及其用途 |
CN1332662C (zh) * | 2005-04-29 | 2007-08-22 | 南京圣和药业有限公司 | 左旋奥硝唑的静脉给药制剂及其制备方法 |
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2005
- 2005-07-08 CN CNB2005100835172A patent/CN1305469C/zh active Active
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2006
- 2006-06-05 ES ES06742090T patent/ES2358441T3/es active Active
- 2006-06-05 WO PCT/CN2006/001204 patent/WO2007006197A1/zh not_active Application Discontinuation
- 2006-06-05 AT AT06742090T patent/ATE493127T1/de not_active IP Right Cessation
- 2006-06-05 EP EP06742090A patent/EP1902712B1/en active Active
- 2006-06-05 US US11/909,623 patent/US20080177083A1/en active Pending
- 2006-06-05 DE DE602006019250T patent/DE602006019250D1/de active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3435049A (en) * | 1965-05-19 | 1969-03-25 | Hoffmann La Roche | Nitroimidazole derivatives |
CS18384A1 (en) * | 1984-01-09 | 1984-11-19 | Marian Ing Simko | Sposob pripravy 1 3 chlor 2 hydroxypropyl 2metyl 5 nitroimi dazolu |
WO1994015922A1 (en) * | 1992-07-31 | 1994-07-21 | Warner Lambert Company | Novel process for preparing chiral [[(2-bromoethyl)amino]methyl]-2-nitro-1h-imidazol-1-ethanol and related compounds |
US5342959A (en) * | 1992-07-31 | 1994-08-30 | Warner-Lambert Company | Process for preparing chiral [[(2-bromoethyl)-amino]methyl]-2-nitro-1H-imidazol-1-ethanol and related compounds |
CN1400312A (zh) * | 2002-08-23 | 2003-03-05 | 中国科学院上海有机化学研究所 | 外消旋奥硝唑的酶法拆分方法 |
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US20080177083A1 (en) | 2008-07-24 |
EP1902712B1 (en) | 2010-12-29 |
CN1709245A (zh) | 2005-12-21 |
DE602006019250D1 (de) | 2011-02-10 |
ES2358441T3 (es) | 2011-05-10 |
WO2007006197A1 (fr) | 2007-01-18 |
EP1902712A1 (en) | 2008-03-26 |
ATE493127T1 (de) | 2011-01-15 |
EP1902712A4 (en) | 2008-09-10 |
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