CN100428964C - RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料及其制备方法 - Google Patents
RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料及其制备方法 Download PDFInfo
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Abstract
一种RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料,由β-磷酸三钙颗粒和RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)两相均匀分散混合组成,两者重量比为1∶10~1∶100。其制法为:先将聚(羟基乙酸-L-赖氨酸-L-乳酸)与GRGDY短肽(甘氨酸-精氨酸-甘氨酸-天冬氨酸-酪氨酸序列)进行聚合反应,生成RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸),再将RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)与β-磷酸三钙颗粒复合即可。该材料既具有良好的生物相容性和细胞亲和性,又具有良好的生物降解性和力学性能,还可以避免组织无菌性坏死,可作为神经导管或多孔骨支架材料,用于神经组织及骨组织缺损修复。
Description
技术领域
本发明涉及组织工程中用于神经组织及骨组织缺损修复的生物材料,具体地指一种用于制作神经导管或多孔骨支架的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料,以及该复合材料的制备方法。
背景技术
组织缺损,比如周围神经缺损,是临床上常见的损伤。传统的治疗方法主要是采用自体的神经、骨骼肌、血管、膜管等天然生物活性材料对其进行修复。但其缺点是需要二次手术,且自体生物活性材料的获取量有限,修复后如果再缺血会产生塌陷,使组织再生不良和粘连,导致吸收疤痕组织增生等。同种异体神经移植也被应用,但其缺点是容易发生免疫反应,并且手术成功率较低。采用非天然生物材料如脱钙骨管、尼龙纤维管、硅胶管、聚氨酯管等,也可以达到修复神经缺损的效果,但这些非天然生物材料不能被人体降解和吸收,需要二次手术取出,这又会对神经组织造成新的损伤。
为了解决上述难题,科研人员一直在努力寻找能有效诱导神经等组织缺损修复的生物降解材料。目前,用于制备神经导管的生物材料主要是一些可降解的天然高分子材料和合成高分子材料。天然高分子材料如胶原、纤维蛋白等,其特定的氨基酸序列使它们具有细胞识别信号,有利于细胞粘附,生物相容性和细胞亲和性好,但缺点是生物降解性能和力学性能较差。合成高分子材料如聚羟基乙酸(PGA)、聚乳酸(PLA)、羟基乙酸和乳酸的共聚物(PLGA)等,其生物降解性能和力学性能都优于天然高分子材料,但其生物相容性、细胞亲和性一般不如天然高分子材料,且其降解产物呈酸性,容易造成组织无菌性坏死。
发明内容
本发明的目的就是要提供一种既具有良好的生物相容性和细胞亲和性、又具有良好的生物降解性和力学性能、还可以有效避免组织无菌性坏死的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料及其制备方法。
为实现上述目的,本发明所提出的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料,由β-磷酸三钙颗粒和RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)两相混合组成,其中:
RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的分子量为3~30万,RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)中L-赖氨酸的摩尔含量为0.1%~5%,RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的分子结构式如下,式中X∶Y=1∶10~1∶500,
β-磷酸三钙颗粒均匀地分散在RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的基体中间,β-磷酸三钙颗粒与RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的重量比在1∶10~1∶100之间。
本发明的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料的制备方法,包括如下步骤:
1)首先将聚(羟基乙酸-L-赖氨酸-L-乳酸)与GRGDY短肽(甘氨酸-精氨酸-甘氨酸-天冬氨酸-酪氨酸序列,Gly-Arg-Gly-Asp-Tyr)进行聚合反应,使GRGDY短肽中的RGD(精氨酸-甘氨酸-天冬氨酸序列,Arg-Gly-Asp)接枝到聚(羟基乙酸-L-赖氨酸-L-乳酸)中的L-赖氨酸的侧氨基上,生成RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸);
2)然后将所生成的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于有机溶剂中,并将β-磷酸三钙颗粒加入到RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的有机溶液中,充分混合均匀;
3)再采用真空干燥的方式,使上述有机溶剂挥发掉,最后获得RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料。
上述聚(羟基乙酸-L-赖氨酸-L-乳酸)通过L-赖氨酸与α-羟基酸(羟基乙酸,L-乳酸)的共聚反应自行制备。具体地可以先将Nε-苄氧羰基-L-赖氨酸与溴乙酰溴进行反应,合成单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮;再将该单体与L-丙交酯聚合,生成聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸);最后将所得聚合物经过钯/碳催化氢解脱苄氧羰基,生成聚(羟基乙酸-L-赖氨酸-L-乳酸)。
上述步骤2)中,有机溶剂为氯仿或乙酸乙酯中的一种。
本发明充分利用了天然高分子材料和合成高分子材料本身固有的优点,将天然高分子材料与合成高分子材料有机地结合为一体,用RGD多肽进行接枝,然后将RGD多肽接枝的聚(羟基乙酸-L-赖氨酸-L-乳酸)与无机材料β-磷酸三钙微粉颗粒进行复合。由于所复合的β-磷酸三钙(β-Ca3(PO4)2,β-TCP)是一种具有良好生物相容性的生物降解陶瓷材料,可用于组织缺损的修复,将其复合到高分子降解材料中后,既可以增加所制作的神经导管的强度,又可以在降解过程中释放出钙离子(Ca2+)和磷酸根离子(PO4 3-),其产物显弱碱性,能中和高分子有机物降解产生的酸性,且钙离子还是促使神经元生长必需的重要物质。而所接枝的多肽含精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp,RGD)序列,能识别细胞,与细胞表面的受体结合,引导细胞粘连,提高细胞的粘附力。因而,本发明的复合材料既具有天然高分子良好的生物相容性和细胞亲和性,有利于细胞粘附;又具有合成高分子材料良好的生物降解性能和力学性能;同时还可以改善高分子材料生物降解产生的酸性环境,有效避免组织无菌性坏死。非常适合作为制备神经导管或多孔骨支架的材料,用于神经组织及骨组织缺损的修复。
附图说明
图1为RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料的1000倍显微结构示意图;
图2为RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料的5000倍显微结构示意图。
具体实施方式
以下结合附图和具体实施例对本发明的复合材料及其制备方法作进一步的详细描述:
实施例1
本发明的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料的制备方法,包括如下步骤:
1)单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮的制备
将50克Nε-苄氧羰基-L-赖氨酸和50毫升三乙胺(Triethylamine,(C2H5)3N)加入到500毫升二氧六环(1,4-Dioxane,C4H8O2)中,在10~25℃的温度条件下滴加30毫升溴乙酰溴(Bromoacetyl Bromide,BrCH2COBr),用薄层色谱法(Thin Layer Chromatography,TLC)跟踪反应,反应完毕后,用乙醚提取反应产物2次,合并提取液,再用水洗提取液2~3次,加入硫酸钠干燥,真空回收溶剂,残留产物用于下步反应。
将上述残留产物在50~110℃的温度条件下滴加到含39g NaHCO3的N,N-二甲基甲酰胺(N,N-Dimethylformamide,DMF)悬浮液1500ml中,用TLC跟踪反应,反应完毕后,真空回收溶剂,用乙酸乙酯提取反应产物数次,合并提取液,用水洗提取液2~3次,然后加入硫酸钠干燥,真空回收溶剂,得蜡状固体,再将蜡状固体溶于乙酸乙酯中,通过柱层析纯化,真空蒸发洗脱液乙酸乙酯,得到单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮的粗品,最后用乙酸乙酯/正己烷重结晶,获得单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮。
2)聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)的制备
按照摩尔比为1∶9分别称取单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮10g和L-丙交酯40.5g,置于干净的安培瓶中,然后注入浓度为30mg/ml的辛酸亚锡氯仿溶液5ml,抽真空使氯仿挥发,在酒精喷灯上将安培瓶熔断封口,置于温度为90~140℃的油浴中聚合12~72小时,生成聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)。
3)聚(羟基乙酸-L-赖氨酸-L-乳酸)的制备
将聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)20克溶于200ml氯仿中,经1克10%的钯/碳催化氢解脱苄氧羰基,生成聚(羟基乙酸-L-赖氨酸-L-乳酸)。
4)RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的制备
将10克聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于300毫升二氯甲烷(Methylene chloride,CH2Cl2)中,同时加入二甲亚砜(Dimethyl Sulfoxide,DMSO)450毫升,再加入0.5~1.6克GRGDY短肽(甘氨酸-精氨酸-甘氨酸-天冬氨酸-酪氨酸序列,Gly-Arg-Gly-Asp-Tyr,GRGDY)和0.5克N,N′-羰基二咪唑(N,N′-Carbonyldiimidazole,CDI),在温度为0~5℃的条件下反应3~5小时,真空回收二氯甲烷(CH2Cl2),残留液变浑浊后,再加入水,析出聚合物,经过滤和高真空干燥,得到分子量为3~15万的目标聚合物——RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸),RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)中L-赖氨酸的摩尔含量为2%~5%。RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的分子结构式如下所示,式中X∶Y=1∶10~1∶500,
5)β-磷酸三钙颗粒的合成
采用固相反应法制备β-磷酸三钙(β-TCP),即将34.4克CaHPO4·2H2O和10克CaCO3混合均匀后,直接在温度940℃左右的条件下烧成制得β-磷酸三钙粉末,然后将β-磷酸三钙粉末加水球磨8~12小时,干燥后在有机溶剂无水乙醇中分散、分级、再干燥,选择β-磷酸三钙粒径在0.05~2μm之间的颗粒备用。
6)RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)与β-磷酸三钙颗粒复合
将10克RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于有机溶剂氯仿或乙酸乙酯中,再将0.2克β-TCP颗粒加入到RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶液中,超声波分散,充分混匀,待溶剂挥发后,形成RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-TCP复合体。
将所制备的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料置于1000倍和5000倍的电子显微镜下观察,其微观结构如图1和图2所示,由图中可以看出β-磷酸三钙颗粒比较均匀地分散在RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的基体中,β-磷酸三钙颗粒的粒径在0.05~2μm之间。
实施例2
1)单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮的制备
将50克Nε-苄氧羰基-L-赖氨酸和50毫升三乙胺加入到500毫升二氧六环中,在10~25℃的温度条件下滴加30毫升溴乙酰溴,用TLC跟踪反应,反应完毕后,用乙醚提取反应产物2次,合并提取液,再用水洗提取液2~3次,加入硫酸钠干燥,真空回收溶剂,残留产物用于下步反应。
将上述残留产物在50~110℃的温度条件下滴加到含39g NaHCO3的DMF悬浮液1500ml中,用TLC跟踪反应,反应完毕后,真空回收溶剂,用乙酸乙酯提取反应产物数次,合并提取液,用水洗提取液2~3次,然后加入硫酸钠干燥,真空回收溶剂,得蜡状固体,再将蜡状固体溶于乙酸乙酯中,通过柱层析纯化,真空蒸发洗脱液乙酸乙酯,得到单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮的粗品,最后用乙酸乙酯/正己烷重结晶,获得单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮。
2)聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)的制备
按照摩尔比为1∶19分别称取单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮5g和L-丙交酯42.75g,置于干净的安培瓶中,然后注入浓度为30mg/ml的辛酸亚锡氯仿溶液5ml,抽真空使氯仿挥发,在酒精喷灯上将安培瓶熔断封口,置于温度为90~140℃的油浴中聚合12~72小时,生成聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)。
3)聚(羟基乙酸-L-赖氨酸-L-乳酸)的制备
将聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)20克溶于200ml氯仿中,经1克10%的钯/碳催化氢解脱苄氧羰基,生成聚(羟基乙酸-L-赖氨酸-L-乳酸)。
4)RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的制备
将10克聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于300毫升二氯甲烷中,同时加入450毫升DMSO,再加入0.2~0.6克GRGDY短肽和0.3克CDI,在温度为0~5℃的条件下反应3~5小时,真空回收二氯甲烷,残留液变浑浊后,再加入水,析出聚合物,经过滤和高真空干燥,得到分子量为5~25万的目标聚合物--RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸),RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)中L-赖氨酸的摩尔含量为1%~2.5%。
5)β-磷酸三钙颗粒的合成
采用固相反应法制备β-磷酸三钙(β-TCP),即将34.4克CaHPO4·2H2O和10克CaCO3混合均匀后,直接在温度940℃左右的条件下烧成制得β-磷酸三钙粉末,然后将β-磷酸三钙粉末加水球磨8~12小时,干燥后在有机溶剂无水乙醇中分散、分级、再干燥,选择β-磷酸三钙粒径在0.05~2μm之间颗粒备用。
6)RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)与β-磷酸三钙颗粒复合
将10克RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于有机溶剂氯仿或乙酸乙酯中,再将0.5克β-TCP颗粒加入到RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶液中超声波分散,充分混匀,待溶剂挥发后,形成RGD多肽接枝聚(羟基乙酸-L-赖
实施例3
1)单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮的制备
将50克Nε-苄氧羰基-L-赖氨酸和50毫升三乙胺加入到500毫升二氧六环中,在10~25℃的温度条件下滴加30毫升溴乙酰溴,用TLC跟踪反应,反应完毕后,用乙醚提取反应产物2次,合并提取液,再用水洗提取液2~3次,加入硫酸钠干燥,真空回收溶剂,残留产物用于下步反应。
将上述残留产物在50~110℃的温度条件下滴加到含39g NaHCO3的DMF悬浮液1500ml中,用TLC跟踪反应,反应完毕后,真空回收溶剂,用乙酸乙酯提取反应产物数次,合并提取液,用水洗提取液2~3次,然后加入硫酸钠干燥,真空回收溶剂,得蜡状固体,再将蜡状固体溶于乙酸乙酯中,通过柱层析纯化,真空蒸发洗脱液乙酸乙酯,得到单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮的粗品,最后用乙酸乙酯/正己烷重结晶,获得单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮。
2)聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)的制备
按照摩尔比为1∶49分别称取单体3-[4-(苄氧羰基氨基)丁基]-吗啉-2,5-二酮2g和L-丙交酯44.2g,置于干净的安培瓶中,然后注入浓度为30mg/ml的辛酸亚锡氯仿溶液5ml,抽真空使氯仿挥发,在酒精喷灯上将安培瓶熔断封口,置于温度为90~140℃的油浴中聚合12~72小时,生成聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)。
3)聚(羟基乙酸-L-赖氨酸-L-乳酸)的制备
将聚(羟基乙酸-Nε-苄氧羰基-L-赖氨酸-L-乳酸)20克溶于200ml氯仿中,经1克10%的钯/碳催化氢解脱苄氧羰基,生成聚(羟基乙酸-L-赖氨酸-L-乳酸)。
4)RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的制备
将10克聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于300毫升二氯甲烷中,同时加入450毫升DMSO,再加入0.03~0.3克GRGDY短肽和0.1克CDI,在温度为0~5℃的条件下反应3~5小时,真空回收二氯甲烷,残留液变浑浊后,再加入水,析出聚合物,经过滤和高真空干燥,得到分子量为8~30万的目标聚合物——RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸),RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)中L-赖氨酸的摩尔含量为0.1%~1%。
5)β-磷酸三钙颗粒的合成
采用固相反应法制备β-磷酸三钙(β-TCP),即将34.4克CaHPO4·2H2O和10克CaCO3混合均匀后,直接在温度940℃左右的条件下烧成制得β-磷酸三钙粉末,然后将β-磷酸三钙粉末加水球磨8~12小时,干燥后在有机溶剂无水乙醇中分散、分级、再干燥,选择β-磷酸三钙粒径在0.05~2μm之间颗粒备用。
6)RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)与β-磷酸三钙颗粒复合
将10克RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于有机溶剂氯仿或乙酸乙酯中,再将1克β-TCP颗粒加入到RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶液中超声波分散,充分混匀,待溶剂挥发后,形成RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-TCP复合体。
Claims (7)
1、一种RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料,其特征在于:该材料由β-磷酸三钙颗粒和RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)两相混合组成,其中:
RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的分子量为3~30万,RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)中L-赖氨酸的摩尔含量为0.1%~5%,RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的分子结构式如下,式中X∶Y=1∶10~1∶500,
β-磷酸三钙颗粒均匀地分散在RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的基体中间,β-磷酸三钙颗粒与RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的重量比在1∶10~1∶100之间。
2、根据权利要求1所述的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料,其特征在于:所说的β-磷酸三钙颗粒的粒径在0.05~2μm之间。
3、根据权利要求1或2所述的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料,其特征在于:所说的β-磷酸三钙颗粒与RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的重量比在1∶10~1∶50之间。
4、一种权利要求1所述的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料的制备方法,包括如下步骤:
1)首先将聚(羟基乙酸-L-赖氨酸-L-乳酸)与GRGDY短肽(甘氨酸-精氨酸-甘氨酸-天冬氨酸-酪氨酸序列,Gly-Arg-Gly-Asp-Tyr)进行聚合反应,使GRGDY短肽中的RGD(精氨酸-甘氨酸-天冬氨酸序列,Arg-Gly-Asp)接枝到聚(羟基乙酸-L-赖氨酸-L-乳酸)中的L-赖氨酸的侧氨基上,生成RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸);
2)然后将所生成的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于有机溶剂氯仿或乙酸乙酯中,并将β-磷酸三钙颗粒加入到RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)的有机溶液中,充分混合均匀;
3)再采用真空干燥的方式,使上述有机溶剂挥发掉,最后获得RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料。
5、根据权利要求4所述的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料的制备方法,其特征在于:所说的步骤1)中,将10克聚(羟基乙酸-L-赖氨酸-L-乳酸)溶于300毫升二氯甲烷中,同时加入450毫升二甲亚砜,再加入0.03~1.6克GRGDY短肽和0.1~0.5克N,N′-羰基二咪唑,在温度为0~5℃的条件下反应3~5小时,真空回收二氯甲烷,残留液变浑浊后,再加入水,析出聚合物,经过滤和高真空干燥,得到分子量为3~30万的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸),RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)中L-赖氨酸的摩尔含量为0.1%~5%。
6、根据权利要求4所述的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料的制备方法,其特征在于:所说的步骤2)中,β-磷酸三钙颗粒的粒径在0.05~2μm之间。
7、根据权利要求4所述的RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)/β-磷酸三钙复合材料的制备方法,其特征在于:所说的步骤2)中,采用超声波分散RGD多肽接枝聚(羟基乙酸-L-赖氨酸-L-乳酸)溶液中的β-磷酸三钙颗粒。
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US9452143B2 (en) | 2012-07-12 | 2016-09-27 | Novus International, Inc. | Matrix and layer compositions for protection of bioactives |
CN103007342B (zh) * | 2012-12-12 | 2014-07-02 | 广东省微生物研究所 | 生物可降解医用磷酸三钙/γ-聚谷氨酸复合材料及其制备方法 |
EP2953581B1 (en) | 2013-02-05 | 2020-09-16 | University of Utah Research Foundation | Implantable devices for bone or joint defects |
CN105688272B (zh) * | 2016-02-02 | 2019-05-24 | 武汉理工大学 | 一种聚合物prgd/聚乳酸/hap-peg的复合定向大孔支架及其制备方法 |
US10584306B2 (en) | 2017-08-11 | 2020-03-10 | Board Of Regents Of The University Of Oklahoma | Surfactant microemulsions |
CN110124101A (zh) * | 2019-06-19 | 2019-08-16 | 成都理工大学 | 一种柠檬酸钙/聚乳酸复合多孔骨组织工程支架材料及其制备方法 |
CN110201239A (zh) * | 2019-06-19 | 2019-09-06 | 成都理工大学 | 一种柠檬酸钙/聚己内酯复合骨修复材料及其应用 |
CN110201238A (zh) * | 2019-06-19 | 2019-09-06 | 成都理工大学 | 一种柠檬酸钙/聚己内酯/聚乳酸骨修复材料及其应用 |
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