CN112500507A - 一种改性聚甲基丙烯酸羟乙酯凝胶和制备方法、药物赋形剂和外用凝胶剂 - Google Patents
一种改性聚甲基丙烯酸羟乙酯凝胶和制备方法、药物赋形剂和外用凝胶剂 Download PDFInfo
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- CN112500507A CN112500507A CN202011403384.3A CN202011403384A CN112500507A CN 112500507 A CN112500507 A CN 112500507A CN 202011403384 A CN202011403384 A CN 202011403384A CN 112500507 A CN112500507 A CN 112500507A
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Abstract
本发明公开了一种聚甲基丙烯酸羟乙酯的羧甲基化改性方法:取聚甲基丙烯酸羟乙酯加入有机溶剂中,充分搅拌使聚甲基丙烯酸羟乙酯呈分散状态,滴加碱水溶液,于35~40℃的恒温条件下碱化反应,反应完成后加入氯乙酸钠,升高反应体系的温度至50~60℃,在恒温搅拌的条件下醚化反应,反应完成后将反应物冷却至室温后将其pH调到6.8~7.2,将产物抽滤,洗涤滤物,干燥,即得羧甲基化改性聚甲基丙烯酸羟乙酯。还公开了改性聚甲基丙烯酸羟乙酯凝胶:包含5~15%羧甲基化改性聚甲基丙烯酸羟乙酯、0.5~0.7%引发剂、0.005~0.1%λ型卡拉胶,余量为水。还公开了含有改性聚甲基丙烯酸羟乙酯凝胶的药物赋形剂和外用凝胶剂。
Description
技术领域
本发明涉及胶体凝胶和医药技术领域,具体涉及一种改性聚甲基丙烯酸羟乙酯凝胶和制备方法、药物赋形剂和外用凝胶剂。
背景技术
聚甲基丙烯酸羟乙酯(PHEMA)是由甲基丙烯酸羟乙酯聚合而得,通常加入多官能团的交联剂,制备PHEMA水凝胶,PHEMA由O.Wichterle等在1960年首次合成,PHEMA具有亲水性,吸水后膨胀至一定体积而且有弹性、柔性、化学惰性、生物惰性,对机体的亲和性良好,并可通过交联程度的调节而改变其弹性模量。之后PHEMA水凝胶就被提出作为一种生物材料,其后被广泛用作软组织替代物和药物释放体系。
由于其具有独特的热可逆凝胶性质和抗蛋白凝结性等特点,聚甲基丙烯酸羟乙酯是凝胶材料中目前应用最为广泛的一种,但是在实际应用中胶体易收缩,具有泌水性、保水性能差的缺点,导致其应用受到限制。
发明内容
本发明的目的是针对上述问题,一方面提供一种聚甲基丙烯酸羟乙酯的羧甲基化改性方法,包括如下步骤:
称取聚甲基丙烯酸羟乙酯加入有机溶剂中,充分搅拌使聚甲基丙烯酸羟乙酯呈分散状态,滴加碱水溶液,于35~40℃的恒温条件下碱化反应,反应完成后加入氯乙酸钠,升高反应体系的温度至50~60℃,在恒温搅拌的条件下醚化反应,反应完成后将反应物冷却至室温后将其pH调到6.8~7.2,将产物抽滤,洗涤滤物,干燥,即得到羧甲基化改性聚甲基丙烯酸羟乙酯。
所述有机溶剂为乙醇水溶液,所述的碱水溶液为氢氧化钠水溶液。
优选地,聚甲基丙烯酸羟乙酯的羧甲基化改性方法,包括如下步骤:称取10~15g聚甲基丙烯酸羟乙酯加入80~100ml体积百分比浓度80%的乙醇溶液中,充分搅拌使聚甲基丙烯酸羟乙酯呈分散状态,以0.5~1ml/min的速度滴加10~15ml重量百分比浓度20%的碱水溶液,在水浴中于恒温35~40℃的条件下碱化反应1~2h;然后加入2~5g氯乙酸钠,升高反应体系的温度至50~60℃,在恒温搅拌的条件下醚化反应3~5h,将反应物冷却至室温后用醋酸将其pH调到7.0,将产物抽滤,滤物用所述的有机溶剂洗涤三次,然后在40℃的恒温鼓风干燥器中干燥即得到羧甲基化改性聚甲基丙烯酸羟乙酯。
本发明的另一方面提供一种改性聚甲基丙烯酸羟乙酯凝胶,包含如下按重量百分比计的组分:5-15%羧甲基化改性聚甲基丙烯酸羟乙酯、0.5~0.7%引发剂、0.005~0.1%λ型卡拉胶,余量为水;
优选所述羧甲基化改性聚甲基丙烯酸羟乙酯是由前述的方法制得;
优选所述引发剂为氯化钾、氯化钙、过氧化月桂酰中的至少一种。
本发明的再一方面提供一种药物赋形剂,包含如下按重量百分比计的组分:5-15%羧甲基化改性聚甲基丙烯酸羟乙酯、0.5~0.7%引发剂、0.005~0.1%λ型卡拉胶、0.01~16%皮肤外用制剂中可以接受的辅料,余量为水;优选所述羧甲基化改性聚甲基丙烯酸羟乙酯是由前述的聚甲基丙烯酸羟乙酯的羧甲基化改性方法制得。
所述药物赋形剂中,所述辅料包括保湿剂、防腐剂、渗透压调节剂和pH调节剂中的至少一种;所述保湿剂占所述凝胶总重量的5~10%,所述防腐剂占所述凝胶总重量的0.01~1%;所述渗透压调节剂占所述凝胶总重量的0.1~5%,所述pH调节剂调节pH至6~8。
优选地,所述保湿剂为乙醇、甘油、丙二醇中的至少一种;所述防腐剂为尼泊金类、三氯叔丁醇、氯甲酚、山梨酸钾、苯甲酸及其钠盐中的至少一种;所述渗透压调节剂为氯化钠、葡萄糖、甘露醇中的至少一种;所述pH调节剂为氢氧化钠、氢氧化钾乙醇胺、乙二胺、乙醇胺、碳酸氢钠中的至少一种。
本发明的再一方面提供一种外用凝胶剂,包含前面任一项所述的药物赋形剂,还包含抗病毒药物或抗生素中的至少一种;
优选所述外用凝胶剂中抗病毒药物或抗生素的质量百分数为0.1~5%。
所述抗病毒药物为干扰素、盐酸金刚烷胺、盐酸金刚乙胺、替洛隆、扎那米韦、奥司他韦、阿替洛韦、利巴韦林、替诺福韦、恩曲他滨等中的至少一种;所述抗生素为氟氯西林、克林霉素、阿奇霉素、罗红霉素、左氧氟沙星等中的至少一种。
本发明的最后一方面提供前述的药物赋形剂的制备方法,包括如下步骤:按照各组分的重量百分比称取各组分,在容器中加入羧甲基化改性聚甲基丙烯酸羟乙酯、引发剂,搅拌,使羧甲基化改性聚甲基丙烯酸羟乙酯充分溶胀,然后加入λ型卡拉胶、皮肤外用制剂中可以接受的辅料混合,加水搅匀,用pH调节剂调节pH为6~8,搅拌30~45min,即得。
本发明的有益效果是:聚甲基丙烯酸羟乙酯形成硬的脆性胶,易发生脱水收缩,改性聚甲基丙烯酸羟乙酯凝胶的糖单元结构中引入羧甲基官能团,由于分子链上的解离态羧基离子之间的静电排斥力作用,凝胶孔隙体积增大,可容纳更多水分子,降低析水率,在保证析水率足够低的同时,由于原结构未被破坏,凝胶还具备一定的凝胶强度,满足软凝胶的特性,具有更好的生物黏附性从而可以更好的粘附在肌肤;加入少量的λ型卡拉胶可以激活炎症反应,诱导自身免疫,引发THP-1单核/巨细胞免疫响应,提高使用部位局部范围的免疫,有效提高巨噬细胞分泌TNF-α,特别是其能够增强脂多糖对巨噬细胞的刺激作用。采用本发明的药物赋形剂结合药物可以应用于皮肤、鼻腔等给药。
附图说明
图1是本发明凝胶的体外累积溶蚀度曲线。
具体实施方式
下面结合实施例对本发明作进一步说明,但并不因此而限制本发明。
下述实施例中的实验方法,如无特别说明,均为常规方法。
主要试剂来源:
聚甲基丙烯酸羟乙酯:CAS号25249-16-5,购自江苏艾康生物医药研发有限公司。
其余试剂如未表明,均为本领域常规试剂,也可商购获得。
实施例1制备药物赋形剂
制备本发明的药物赋形剂,按照如下步骤进行:按照各组分的重量百分比称取各组分,在容器中加入羧甲基化改性聚甲基丙烯酸羟乙酯、引发剂,搅拌,使羧甲基化改性聚甲基丙烯酸羟乙酯充分溶胀,然后加入λ型卡拉胶、渗透压调节剂、保湿剂、防腐剂混合,加水搅匀,用pH调节剂调节pH为6~8,搅拌30~45min,即得。
按照此方法制备实验例1、2、3的药物赋形剂凝胶样品,并且按此方法制备对比例1和2,各样品的具体组分和配比如表1所示(表中各组分的含量为质量百分数,余量为水)。对比例1相对于实验例1区别在于不使用羧甲基化改性聚甲基丙烯酸羟乙酯,而是直接添加的聚甲基丙烯酸羟乙酯;对比例2相对于实验例1区别在于不含有卡拉胶。
表1
实验例1和对比例2中的羧甲基化改性聚甲基丙烯酸羟乙酯的制备方法如下:
称取10g聚甲基丙烯酸羟乙酯加入80ml 80%(v/v)的乙醇溶液中,充分搅拌使聚甲基丙烯酸羟乙酯呈分散状态,以0.5ml/min的速度滴加10ml 20%(w/w)的NaOH水溶液,在水浴中于恒温35℃的条件下碱化反应1h;然后加入2g氯乙酸钠,升高反应体系的温度至50℃,在恒温搅拌的条件下醚化反应3h,将反应物冷却至室温后用醋酸将其pH调到7.0左右,将产物抽滤,滤物用80%的乙醇溶液洗涤三次,然后在40℃的恒温鼓风干燥器中干燥即得到羧甲基化改性聚甲基丙烯酸羟乙酯。
实验例2和3中的羧甲基化改性聚甲基丙烯酸羟乙酯的制备方法如下:
称取15g聚甲基丙烯酸羟乙酯加入100ml 80%(v/v)的乙醇溶液中,充分搅拌使聚甲基丙烯酸羟乙酯呈分散状态,以1ml/min的速度滴加15ml 20%(w/w)的NaOH水溶液,在水浴中于恒温40℃的条件下碱化反应2h;然后加入5g氯乙酸钠,升高反应体系的温度至60℃,在恒温搅拌的条件下醚化反应5h,将反应物冷却至室温后用醋酸将其pH调到7.0左右,将产物抽滤,滤物用80%的乙醇溶液洗涤三次,然后在40℃的恒温鼓风干燥器中干燥即得到羧甲基化改性聚甲基丙烯酸羟乙酯。
实施例2凝胶析水率测定
分别精确称取5g实验例1-3中刚制备得到的药物赋形剂,用滤纸吸干凝胶表面水珠后再次进行精确称重。
析水率计算公式:
式中K为凝胶析水率;
m1为初始凝胶质量;
m2为除去表面水份后凝胶质量。
计算得到析水率结果如表2所示:实验例1-3所得凝胶不具有析水率,说明凝胶不会因脱水而体积缩小,凝胶具有较好的稳定性;相比之下,对比例1的吸水率过高。
表2析水率
实施例3质构性质分析
采用博勒飞CT3质构仪考察药物赋形剂的凝胶强度和胶着性。选择圆柱形P/0.5探头,设定测试为下压模式,以1mm/s的速度降低探头,触发力为5g。当探头接触样品表面后,探头以2mm/s下压至10mm,然后以10mm/s的速度回升。记录应力—时间曲线,处理图形,得到凝胶强度为正峰的最大值和胶着性为负峰的面积。
实验例1-3的凝胶强度和胶着性实验结果如表3所示:本发明的药物赋形剂凝胶,质地较软,凝胶强度和胶着力较高。对比例1凝胶的强度及胶着力相对较弱,影响凝胶质量及使用效果。
表3质构性质分析结果
实施例4粘度测定
仪器选用博勒飞DV-C数显旋转型粘度计,选择S62转子,转速设置成60r·min-1,样品置于恒温水浴并且控制样品温度保持在25℃,测定样品溶液的粘度,每个样品平行测定三次。实验例1-3的药物赋形剂凝胶粘度实验结果如表4所示:对比例1凝胶粘度较低,凝胶较稀,影响药物滞留时间。
表4粘度测定结果
实施例5溶蚀实验
将实验例1中的药物赋形剂凝胶装入西林瓶中,密封,称重,37℃凝固,精密加入预热至37℃的释放介质PBS缓冲液1ml,密封,摇床中振荡20min,小心吸出上层液体,再次称重,得失重。重复操作,直至凝胶溶蚀完全,然后以累积溶蚀重量为纵坐标,时间为横坐标制图,得体外累积溶蚀度曲线,如图1所示,表明凝胶溶蚀重量与时间成正比,表明凝胶溶蚀是控制药物释放的主要因素。
实施例6检测TNF-α的表达量
THP-1细胞(常规商购获得)用含10%胎牛血清、青霉素(100U/mL)、链霉素(100ug/ml)的RPMI-1640培养基,置于37℃、5%CO2培养箱中常规培养。将细胞接种于不同规格的培养板中,立即加入丙二醇甲醚醋酸酯(PMA,终浓度100ng/mL),诱导48h,使其完全分化为巨噬细胞。
在分化完全的THP-1巨噬细胞中分别加入实验例1-3和对比例2的凝胶样品,24h后收集上清液,4℃,1000r/min离心10min,检测上清液中TNF-α的表达量,结果如表5所示,可知加入少量的λ型卡拉胶激活炎症反应,诱导自身免疫,引发THP-1单核/巨细胞免疫响应,提高使用部位局部范围的免疫,有效提高巨噬细胞分泌TNF-α。
表5 TNF-α的表达量
最后说明的是,以上实施例仅用以说明本发明的技术方案而非限制,尽管参照较佳实施例对本发明进行了详细说明,本领域的普通技术人员应当理解,可以对本发明的技术方案进行修改或者等同替换,而不脱离本技术方案的宗旨和范围,其均应涵盖在本发明的权利要求范围当中。
Claims (10)
1.一种聚甲基丙烯酸羟乙酯的羧甲基化改性方法,其特征在于,包括如下步骤:
称取聚甲基丙烯酸羟乙酯加入有机溶剂中,充分搅拌使聚甲基丙烯酸羟乙酯呈分散状态,滴加碱水溶液,于35~40℃的恒温条件下碱化反应,反应完成后加入氯乙酸钠,升高反应体系的温度至50~60℃,在恒温搅拌的条件下醚化反应,反应完成后将反应物冷却至室温后将其pH调到6.8~7.2,将产物抽滤,洗涤滤物,干燥,即得到羧甲基化改性聚甲基丙烯酸羟乙酯。
2.如权利要求1所述的聚甲基丙烯酸羟乙酯的羧甲基化改性方法,其特征在于,所述有机溶剂为乙醇水溶液,所述的碱水溶液为氢氧化钠水溶液。
3.如权利要求1或2所述的聚甲基丙烯酸羟乙酯的羧甲基化改性方法,其特征在于,包括如下步骤:称取10~15g聚甲基丙烯酸羟乙酯加入80~100ml体积百分比浓度80%的乙醇溶液中,充分搅拌使聚甲基丙烯酸羟乙酯呈分散状态,以0.5~1ml/min的速度滴加10~15ml重量百分比浓度20%的碱水溶液,在水浴中于恒温35~40℃的条件下碱化反应1~2h;然后加入2~5g氯乙酸钠,升高反应体系的温度至50~60℃,在恒温搅拌的条件下醚化反应3~5h,将反应物冷却至室温后用醋酸将其pH调到7.0,将产物抽滤,滤物用所述的有机溶剂洗涤三次,然后在40℃的恒温鼓风干燥器中干燥即得到羧甲基化改性聚甲基丙烯酸羟乙酯。
4.一种改性聚甲基丙烯酸羟乙酯凝胶,其特征在于:包含如下按重量百分比计的组分:5-15%羧甲基化改性聚甲基丙烯酸羟乙酯、0.5~0.7%引发剂、0.005~0.1%λ型卡拉胶,余量为水;
优选所述羧甲基化改性聚甲基丙烯酸羟乙酯是由权利要求1至3任一项所述的方法制得;
优选所述引发剂为氯化钾、氯化钙、过氧化月桂酰中的至少一种。
5.一种药物赋形剂,其特征在于:包含如下按重量百分比计的组分:5-15%羧甲基化改性聚甲基丙烯酸羟乙酯、0.5~0.7%引发剂、0.005~0.1%λ型卡拉胶、0.01~16%皮肤外用制剂中可以接受的辅料,余量为水;优选所述羧甲基化改性聚甲基丙烯酸羟乙酯是由权利要求1或2的方法制得。
6.如权利要求5所述的药物赋形剂,其特征在于:所述辅料包括保湿剂、防腐剂、渗透压调节剂和pH调节剂中的至少一种;所述保湿剂占所述凝胶总重量的5~10%,所述防腐剂占所述凝胶总重量的0.01~1%;所述渗透压调节剂占所述凝胶总重量的0.1~5%,所述pH调节剂调节pH至6~8。
7.如权利要求6所述的药物赋形剂,其特征在于:所述保湿剂为乙醇、甘油、丙二醇中的至少一种;所述防腐剂为尼泊金类、三氯叔丁醇、氯甲酚、山梨酸钾、苯甲酸及其钠盐中的至少一种;所述渗透压调节剂为氯化钠、葡萄糖、甘露醇中的至少一种;所述pH调节剂为氢氧化钠、氢氧化钾乙醇胺、乙二胺、乙醇胺、碳酸氢钠中的至少一种。
8.一种外用凝胶剂,其特征在于:包含权利要求4至7中任一项所述的药物赋形剂,还包含抗病毒药物或抗生素中的至少一种;
优选所述外用凝胶剂中抗病毒药物或抗生素的质量百分数为0.1~5%。
9.如权利要求8所述的外用凝胶剂,其特征在于:所述抗病毒药物为干扰素、盐酸金刚烷胺、盐酸金刚乙胺、替洛隆、扎那米韦、奥司他韦、阿替洛韦、利巴韦林、替诺福韦、恩曲他滨等中的至少一种;所述抗生素为氟氯西林、克林霉素、阿奇霉素、罗红霉素、左氧氟沙星等中的至少一种。
10.权利要求5至7任一项所述的药物赋形剂的制备方法,其特征在于,包括如下步骤:按照各组分的重量百分比称取各组分,在容器中加入羧甲基化改性聚甲基丙烯酸羟乙酯、引发剂,搅拌,使羧甲基化改性聚甲基丙烯酸羟乙酯充分溶胀,然后加入λ型卡拉胶、皮肤外用制剂中可以接受的辅料混合,加水搅匀,用pH调节剂调节pH为6~8,搅拌30~45min,即得。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000069393A1 (en) * | 1999-05-13 | 2000-11-23 | 3M Innovative Properties Company | Fluoride releasing orthodontic adhesive |
CN101342174A (zh) * | 2008-08-26 | 2009-01-14 | 北京天川军威医药技术开发有限公司 | 一种酞丁安/达克罗宁的复方局部用制剂 |
FR2934268A1 (fr) * | 2008-07-24 | 2010-01-29 | Oreal | Polymeres a greffons polysaccharidiques, compositions cosmetiques et procede de traitement. |
CN104072677A (zh) * | 2013-03-27 | 2014-10-01 | 广州都邦材料科技有限公司 | 具有半互穿网络结构高分子水凝胶的制备方法 |
CN110204742A (zh) * | 2019-07-15 | 2019-09-06 | 吉林大学 | 一种仿眼角膜的高强度电响应润滑水凝胶及其制备方法 |
CN111437270A (zh) * | 2020-04-24 | 2020-07-24 | 瑞希(重庆)生物科技有限公司 | 一种卡拉胶鼻用即型凝胶喷雾剂及其制备方法 |
-
2020
- 2020-12-02 CN CN202011403384.3A patent/CN112500507A/zh active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000069393A1 (en) * | 1999-05-13 | 2000-11-23 | 3M Innovative Properties Company | Fluoride releasing orthodontic adhesive |
FR2934268A1 (fr) * | 2008-07-24 | 2010-01-29 | Oreal | Polymeres a greffons polysaccharidiques, compositions cosmetiques et procede de traitement. |
CN101342174A (zh) * | 2008-08-26 | 2009-01-14 | 北京天川军威医药技术开发有限公司 | 一种酞丁安/达克罗宁的复方局部用制剂 |
CN104072677A (zh) * | 2013-03-27 | 2014-10-01 | 广州都邦材料科技有限公司 | 具有半互穿网络结构高分子水凝胶的制备方法 |
CN110204742A (zh) * | 2019-07-15 | 2019-09-06 | 吉林大学 | 一种仿眼角膜的高强度电响应润滑水凝胶及其制备方法 |
CN111437270A (zh) * | 2020-04-24 | 2020-07-24 | 瑞希(重庆)生物科技有限公司 | 一种卡拉胶鼻用即型凝胶喷雾剂及其制备方法 |
Non-Patent Citations (5)
Title |
---|
QIAN GARRETT,等: "Effect of charged groups on the adsorption and penetration of proteins onto and into carboxymethylated poly(HEMA) hydrogels", 《BIOMATERIALS》 * |
Y.H.HUI,等: "《贝雷:油脂化学与工艺学 第5卷》", 30 June 2001, 中国轻工业出版社 * |
杨超超: "温敏型可注射水凝胶的结构设计及其可注射性能", 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》 * |
罗明生,等: "《药剂辅料大全 第2版》", 31 January 2006, 四川科学技术出版社 * |
许瞳: "抗生物黏附微结构水凝胶材料的研究", 《中国博士学位论文全文数据库工程科技Ⅰ辑》 * |
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