CN113773269A - 氟雷拉纳的晶型及其制备方法 - Google Patents
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- QNFBKOHHLAWWTC-UHFFFAOYSA-N Fraxidin Chemical compound C1=CC(=O)OC2=C1C=C(OC)C(OC)=C2O QNFBKOHHLAWWTC-UHFFFAOYSA-N 0.000 description 10
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Abstract
本发明公开了式I氟雷拉纳的新晶型及其制备方法，还公开了含有这些晶型的药物组合物和用途。
Description
技术领域
本发明涉及氟雷拉纳的晶型、其制备方法和含有这些晶型的药物组合物。
背景技术
氟雷拉纳是一种新型广谱兽药，属于异唑啉类动物杀虫剂，通过干预γ-氨基丁酸(GABA)门控氯离子通道发挥其作用，与苯基吡唑类，环戊二烯类和大环内酯类等动物杀虫剂相比较而言，氟雷拉纳在分子结构、作用位点、选择性以及交互抗性等方面均有者显著的差异，具有对哺乳动物安全、杀虫活性较高等特性。
氟雷拉钠由英特威公司申请上市，于2014年5月25日获得美国食品药品监督管理局(FDA)批准上市。
氟雷拉纳的分子式为C22H17Cl2F6N3O3，分子量为556.29，其结构式I如下所示：
迄今为止，尚未有专利保护氟雷拉纳的晶型及制备方法，更未提及有关晶型的光谱特性。
发明内容
本发明公开了一种氟雷拉纳的晶型A。所述晶型A的X射线粉末衍射图的特征峰以2θ(±0.2°2θ)表示位于4.36°、8.72°、21.17°、21.89°、24.96°、26.34°；优选地，特征峰位于4.36°、8.72°、18.79°、21.17°、21.89°、23.84°、24.96°、26.34°；更优选地，所述晶型A的X射线粉末衍射图的特征峰如图1所示。该晶型DSC数据表明在峰值170℃显示吸热如图2所示。
本发明的又一目的在于，提供制备氟雷拉纳晶型A的方法，晶型A的制备包括将氟雷拉纳溶解在有机溶剂中，然后升温溶解，室温析晶。
优选地，氟雷拉纳溶解在异丙醇或者乙酸乙酯和正庚烷的混合溶剂中，溶解温度为回流温度。
更优选地，乙酸乙酯和正庚烷的比例为1:2。
本发明还公开了含有氟雷拉纳晶型A的药物组合，其含有有效量的氟雷拉纳晶型A和药学上可接受的辅料。其剂型可以是片剂(如肠溶片、包衣片、薄膜衣片、糖衣片、浸膏片、分散片、划痕片等)、硬胶囊、软胶囊(胶丸)、肠溶胶囊、缓释控释剂型、缓释片、缓释包衣、注射剂及其他任何可适合临床给药的剂型。该药物组合适用于治疗犬跳蚤、蜱虫感染。
附图说明
图1是氟雷拉纳晶型A的X射线衍射图；
图2是氟雷拉纳晶型A的DSC图谱。
具体实施方式
通过下面的实施例可以更具体的理解本发明，但其是举例说明而不是限制本发明的范围。
实施例
1.制备氟雷拉纳晶型A
氟雷拉纳(10g)溶于异丙醇(25ml)，然后升温至回流溶解，完毕后室温搅拌析晶，得到固体8g。
2.制备氟雷拉纳晶型A
氟雷拉纳(10g)溶于乙酸乙酯/正庚烷(30ml，V/V＝1:2)，然后升温至回流溶解，完毕后室温搅拌析晶，得到固体7.5g。
结合图1和图2可以发现本发明的晶型是氟雷拉纳晶型A。
Claims (5)
1.式I所示氟雷拉纳的晶型结构，
2.如权利要求1所述的晶型结构A，所述晶型A的X射线粉末衍射图的特征峰以2θ(±0.2°2θ)表示位于4.36°、8.72°、21.17°、21.89°、24.96°、26.34°；优选地，特征峰位于4.36°、8.72°、18.79°、21.17°、21.89°、23.84°、24.96°、26.34°；更优选地，所述晶型A的X射线粉末衍射图的特征峰如图1所示。
3.如权利要求2所述的晶型结构，其特征在于，DSC数据表明在峰值170℃显示吸热，如图2所示。
4.一种药物组合，它含有权利要求1中所示的式I化合物的A晶型和药学上可接受的辅料。
5.如权利要求4的药物组合物，其特征在于：所述药物组合物的剂型可以是片剂(如肠溶片、包衣片、薄膜衣片、糖衣片、浸膏片、分散片、划痕片等)、硬胶囊、软胶囊(胶丸)、肠溶胶囊、缓释控释剂型、缓释片、缓释包衣、注射剂及其他任何可适合临床给药的剂型。
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1930136A (zh) * | 2004-03-05 | 2007-03-14 | 日产化学工业株式会社 | 异噁唑啉取代苯甲酰胺化合物及有害生物防除剂 |
| CN102149695A (zh) * | 2008-07-09 | 2011-08-10 | 日产化学工业株式会社 | 异*唑啉取代的苯甲酰胺化合物的制造方法 |
| CN107501199A (zh) * | 2017-08-16 | 2017-12-22 | 南京农业大学 | 氟雷拉纳单体化合物的提取和纯化方法 |
| CN109879826A (zh) * | 2019-03-18 | 2019-06-14 | 丽珠集团新北江制药股份有限公司 | 一种异噁唑啉类杀虫剂的制备方法 |
| CN110596268A (zh) * | 2019-09-20 | 2019-12-20 | 天津市中升挑战生物科技有限公司 | 一种氟雷拉纳消旋体中异构体的分离检测方法 |
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2020
- 2020-06-09 CN CN202010516669.1A patent/CN113773269A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1930136A (zh) * | 2004-03-05 | 2007-03-14 | 日产化学工业株式会社 | 异噁唑啉取代苯甲酰胺化合物及有害生物防除剂 |
| CN101768129A (zh) * | 2004-03-05 | 2010-07-07 | 日产化学工业株式会社 | 异*唑啉取代苯甲酰胺化合物的制备中间体 |
| CN102149695A (zh) * | 2008-07-09 | 2011-08-10 | 日产化学工业株式会社 | 异*唑啉取代的苯甲酰胺化合物的制造方法 |
| CN107501199A (zh) * | 2017-08-16 | 2017-12-22 | 南京农业大学 | 氟雷拉纳单体化合物的提取和纯化方法 |
| CN109879826A (zh) * | 2019-03-18 | 2019-06-14 | 丽珠集团新北江制药股份有限公司 | 一种异噁唑啉类杀虫剂的制备方法 |
| CN110596268A (zh) * | 2019-09-20 | 2019-12-20 | 天津市中升挑战生物科技有限公司 | 一种氟雷拉纳消旋体中异构体的分离检测方法 |
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