CN106420663A - 聚己内酯载利福喷丁微球的制备方法 - Google Patents
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 21
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- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 229960003292 rifamycin Drugs 0.000 description 1
- HJYYPODYNSCCOU-ODRIEIDWSA-N rifamycin SV Chemical compound OC1=C(C(O)=C2C)C3=C(O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O HJYYPODYNSCCOU-ODRIEIDWSA-N 0.000 description 1
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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Abstract
本发明公开了聚己内酯载利福喷丁微球的制备方法,包含以下步骤:将利福喷丁原药、聚己内酯20共溶于二氯甲烷中,超声处理,形成油相;将形成的油相滴加至2%的聚乙烯醇水溶液中,在3000rpm的转速下机械搅拌30min,密封、静置30 min后,在100rpm的转速下持续搅拌3h,形成乳液;离心处理,得到的固体用蒸馏水洗涤,再次离心分离、洗涤,最后在冷冻真空干燥机中干燥,得到聚己内酯载利福喷丁微球,放置在‑4℃下避光保存。本发明制备的聚己内酯载利福喷丁微球形态圆整,表面有微孔结构,粒径分散性好,载药量高,具有良好的缓释作用,所制备的微球可以用于骨与关节结核的长效介入治疗。
Description
技术领域
本发明属于载药微球的制备领域,具体涉及一种聚己内酯载利福喷丁微球的制备方法。
背景技术
骨与关节结核长期以来严重影响患者健康和生活质量,其治疗过程中常选择口服或静脉制剂全身用药,但都难以达到有效的药物浓度,也有在手术结束时于术区局部放置抗结核药物,但局部的药物会随血液循环和自身代谢迅速消失。局部载药系统可以调节药物释放速度,降低药物毒副作用,长时间维持有效的药物浓度,从而提高疗效。
可降解载药微球已被证实是一种高效、低毒副作用的药物缓释控制体系,近来受到研究者的广泛关注。载药微球载体与微球的形貌、降解及释药等息息相关,因此其选择至关重要。聚己内酯(PCL)是一种人工合成的聚酯类生物高分子材料,可生物降解,生物相容性好,是具有长效降解机制的疏水性聚合物,其最终降解产物将被机体吸收和排泄到体外,被广泛应用于缓释微球的控制体系。利福喷丁(RFT)是一种半合成的长效利福霉素族抗生素,其对结核杆菌的抗菌能力与利福平相比要高2~10倍,不良反应较少。但其分子量大,脂溶性强,对人体组织穿透力强,口服给药后广泛分布于全身组织及体液,以肝肾肺深度最高,主要以原型及代谢物形式自粪便排泄,生物利用度低。若将利福喷丁包裹于微球制成抗结核缓释微球,可原位缓慢释放提高生物利用度,减少对肝功能的毒副作用。
目前聚己内酯被用于负载利福喷丁构建长效微球缓释系统的研究较少,制备产品效果差、载药量少、抗菌性差。
发明内容
本发明提供一种聚己内酯载利福喷丁微球的制备方法。
本发明是通过以下技术方案实现的。
聚己内酯载利福喷丁微球的制备方法,包含以下步骤:
(1)称取利福喷丁原药10-50 mg、聚己内酯200-300mg共溶于10-15mL二氯甲烷中,超声处理,形成油相;
(2)将步骤(1)形成的油相滴加至100-150mL、质量分数为2%的聚乙烯醇水溶液中,在3000rpm的转速下机械搅拌30min,密封、静置30 min后,在100rpm的转速下持续搅拌3h,形成乳液;
(3)将步骤(2)得到的乳液离心处理,得到的固体用蒸馏水洗涤,再次离心分离、洗涤,最后在冷冻真空干燥机中干燥,得到聚己内酯载利福喷丁微球,放置在-4℃下避光保存。
优选地,步骤(1)中,超声处理的条件为:超声功率200W,超声时间30min。
优选地,步骤(1)中,将利福喷丁原药34 mg、聚己内酯235mg共溶于13mL二氯甲烷中,进行超声处理。
优选地,步骤(2)中,离心转速为1000rpm、离心时间为30min。
本发明的优点:
本发明采用O/W乳化溶剂挥发法制备了载利福喷丁聚己内酯微球,得到的微球形态圆整,表面有微孔结构,粒径分散性好,载药量高,具有良好的缓释作用,所制备的微球可以用于骨与关节结核的长效介入治疗。
具体实施方式
实施例1
聚己内酯载利福喷丁微球的制备方法,包含以下步骤:
(1)称取利福喷丁原药10-50 mg、聚己内酯200-300mg共溶于10-15mL二氯甲烷中,超声处理,形成油相;
(2)将步骤(1)形成的油相滴加至100-150mL、质量分数为2%的聚乙烯醇水溶液中,在3000rpm的转速下机械搅拌30min,密封、静置30 min后,在100rpm的转速下持续搅拌3h,形成乳液;
(3)将步骤(2)得到的乳液离心处理,得到的固体用蒸馏水洗涤,再次离心分离、洗涤,最后在冷冻真空干燥机中干燥,得到聚己内酯载利福喷丁微球,放置在-4℃下避光保存。
实施例2
聚己内酯载利福喷丁微球的制备方法,包含以下步骤:
(1)称取利福喷丁原药34mg、聚己内酯235mg共溶于13mL二氯甲烷中,超声处理,其中,超声功率200W,超声时间30min,形成油相;
(2)将步骤(1)形成的油相滴加至100-150mL、质量分数为2%的聚乙烯醇水溶液中,在3000rpm的转速下机械搅拌30min,密封、静置30 min后,在100rpm的转速下持续搅拌3h,形成乳液;
(3)将步骤(2)得到的乳液离心处理,得到的固体用蒸馏水洗涤,再次离心分离、洗涤,其中,离心转速为1000rpm、离心时间为30min,最后在冷冻真空干燥机中干燥,得到聚己内酯载利福喷丁微球,放置在-4℃下避光保存。
Claims (4)
1.聚己内酯载利福喷丁微球的制备方法,其特征在于:包含以下步骤:
(1)称取利福喷丁原药10-50 mg、聚己内酯200-300mg共溶于10-15mL二氯甲烷中,超声处理,形成油相;
(2)将步骤(1)形成的油相滴加至100-150mL、质量分数为2%的聚乙烯醇水溶液中,在3000rpm的转速下机械搅拌30min,密封、静置30 min后,在100rpm的转速下持续搅拌3h,形成乳液;
(3)将步骤(2)得到的乳液离心处理,得到的固体用蒸馏水洗涤,再次离心分离、洗涤,最后在冷冻真空干燥机中干燥,得到聚己内酯载利福喷丁微球,放置在-4℃下避光保存。
2.根据权利要求1所述的聚己内酯载利福喷丁微球的制备方法,其特征在于:步骤(1)中,超声处理的条件为:超声功率200W,超声时间30min。
3.根据权利要求1所述的聚己内酯载利福喷丁微球的制备方法,其特征在于:步骤(1)中,将利福喷丁原药34 mg、聚己内酯235mg共溶于13mL二氯甲烷中,进行超声处理。
4.根据权利要求1所述的聚己内酯载利福喷丁微球的制备方法,其特征在于:步骤(2)中,离心转速为1000rpm、离心时间为30min。
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN108559357A (zh) * | 2018-04-17 | 2018-09-21 | 北京科技大学 | 一种热响应复合自修复涂层及其制备方法 |
CN110036947A (zh) * | 2019-04-23 | 2019-07-23 | 深圳信息职业技术学院 | 一种诱导珊瑚浮浪幼虫提高附着能力的方法 |
CN113952520A (zh) * | 2021-10-18 | 2022-01-21 | 上海玮沐医疗科技有限公司 | 一种含有聚己内酯的聚乙烯醇微球及其制备方法 |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108559357A (zh) * | 2018-04-17 | 2018-09-21 | 北京科技大学 | 一种热响应复合自修复涂层及其制备方法 |
CN110036947A (zh) * | 2019-04-23 | 2019-07-23 | 深圳信息职业技术学院 | 一种诱导珊瑚浮浪幼虫提高附着能力的方法 |
CN113952520A (zh) * | 2021-10-18 | 2022-01-21 | 上海玮沐医疗科技有限公司 | 一种含有聚己内酯的聚乙烯醇微球及其制备方法 |
CN113952520B (zh) * | 2021-10-18 | 2022-09-02 | 上海玮沐医疗科技有限公司 | 一种含有聚己内酯的聚乙烯醇微球及其制备方法 |
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