CN118161668B - 一种温度敏感性羊膜凝胶材料及制备方法及应用 - Google Patents
一种温度敏感性羊膜凝胶材料及制备方法及应用 Download PDFInfo
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Abstract
本发明公开了一种温度敏感性羊膜凝胶材料及制备方法及应用,属于生物医用材料技术领域,包含以下浓度的组份:羊膜冻干粉末0.1~5wt%、卡波姆0.1~5wt%、泊洛沙姆20~35wt%、正电荷特性多肽1~10wt%、负电荷特性多肽1~10wt%,其余为生理盐水。该材料能够快速形成凝胶状从而避免流动到其他非靶向区域,可以延长其在创面靶向区域的驻留时间,从而提高羊膜的促进组织再生作用效果,可在眼科、骨科或神经外科手术中具有良好的应用前景。
Description
技术领域
本发明属于生物医用材料技术领域,具体涉及一种温度敏感性羊膜凝胶材料及制备方法及应用。
背景技术
羊膜,特别是人源羊膜,作为组织再生型生物医用材料已在临床外科手中具有广泛的应用,其形态多为膜片状、悬液状、干粉状或凝胶状,具有促进上皮愈合、抑制炎性反应、减少瘢痕形成和抗菌性等作用,在眼科领域中广泛用于眼表疾病的治疗。
在羊膜凝胶医用材料的应用中,有很多领域需要其具有温度敏感性。例如,对于人体眼科、骨科等手术中,需要赋予羊膜凝胶温度敏感特性,即材料在注射时具有低粘度、良好的可注射性,但是在注射到人体创面接触后,由于人体温度一般大约在37℃,在温度的引发作用下,羊膜材料可以快速形成凝胶状从而避免流动到其他非靶向区域,可以延长其在创面靶向区域的驻留时间,提高其作用效果。因此,开发具有温度敏感性的羊膜凝胶材料具有很大的临床需求及应用价值。
温度敏感性水凝胶在低温下为液态,高温时凝聚,且这种状态的变化随温度可逆。它同时具有聚合材料的多种特征,如网络结构和高含水量,广泛的运用于医药、生命科学等多种领域,包括但不仅限于细胞3D培养、组织工程和药物传送这些。现有公开文献资料中报道的温度敏感性水凝胶材料包括:异丙基丙烯酰胺聚合物(参考文献:可视化温敏变色型实时体温监测复合水凝胶的制备与应用.当代化工研究,2023(18):43-45.),温敏性胶原(参考文献:专利:一种仿生胶原水溶液及其制备方法和使用方法,申请号:202011152941.9;论文:Rapid sol-gel reversible thermosensitive collagen for 3D cell culture.Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2024, 681,132813.),基于金刚烷-环糊精自组装作用形成的温敏性水凝胶(参考文献:专利:超分子材料、自愈合温敏性水凝胶及其制备方法,申请号:201811640303 .4),壳聚糖温敏性水凝胶(参考文献:专利:一种温敏性水凝胶的制备方法,申请号:202310999679.9),等等。但目前未见公开报道有制备温度敏感性羊膜凝胶材料的参考技术方法。
发明内容
本发明旨在弥补现有羊膜凝胶材料不具备温度敏感特性方面的空白,提出了一种温度敏感性羊膜凝胶材料,该材料以羊膜冻干粉末、卡波姆、泊洛沙姆、正电荷特性多肽、负电荷特性多肽为有效成分制得,能够快速形成凝胶状从而避免流动到其他非靶向区域,可以延长其在创面靶向区域的驻留时间,从而提高羊膜的促进组织再生作用效果。为此,本发明还提供了该温度敏感性羊膜凝胶材料的制备方法及其应用,可应用于眼科、骨科或神经外科手术中。
本发明通过下述技术方案实现:一种温度敏感性羊膜凝胶材料,包含以下浓度的组份:羊膜冻干粉末0.1~5wt%、卡波姆0.1~5wt%、泊洛沙姆20~35wt%、正电荷特性多肽1~10wt%、负电荷特性多肽1~10wt%,其余为生理盐水。
进一步的,所述正电荷特性多肽的氨基酸序列为RRHKHRR(Arg-Arg-His-Lys-His-Arg-Arg),其电荷量为5~10mV;所述负电荷特性多肽的氨基酸序列为DDDKEEE(Asp-Asp-Asp-Lys-Glu-Glu-Glu),其电荷量为-10~-5mV。
所述正电荷特性多肽的结构式如下式(1)所示:
(1)。
所述负电荷特性多肽的结构式如下式(2)所示:
(2)。
所述羊膜冻干粉末是以羊膜为原料,经清洗、晾干、冰浴粉碎获得羊膜提取物后,再经冷冻干燥而制得。
所述冰浴粉碎是将晾干后的羊膜与冰块混合形成冰水羊膜混合液后再进行粉碎的过程,其中将冰块与羊膜混合时,控制冰块与羊膜的质量比为1∶1~5∶1。
所述粉碎时,每次粉碎10~60S,停止1min,重复此过程30~90次。
如上述温度敏感性羊膜凝胶材料的制备方法,按配比,配制羊膜冻干粉末的水溶液,将卡波姆、泊洛沙姆以及正电荷特性多肽加入到羊膜冻干粉末的水溶液中,即得组分A;配制负电荷特性多肽的水溶液,即得组分B;将组分A和组分B混合后,即得。
如上述温度敏感性羊膜凝胶材料在制备医用材料中的应用,所述医用材料包括眼科、骨科或神经外科手术用羊膜水凝胶。
所述羊膜水凝胶在常温下为流体,在35~43℃下,于10s~1min内从流体转变固态。
优选地,所述的泊洛沙姆为泊洛沙姆407。
优选地,所述的卡波姆为卡波姆981。
进一步需要说明的是,本发明所述羊膜来自于人体以及其他哺乳动物,包括猪、牛、羊,其中,人源羊膜(来自人体的)是经过伦理审查和捐赠者的知情同意等程序后,从合法、正规医院取得,获取途径合法、合规。所述常温为25℃。所述流体是指具有流动性的液体。所述固态是指不具有流动性的凝胶体。
本发明与现有技术相比,具有以下优点及有益效果:
(1)本发明通过将羊膜冻干粉末、卡波姆、泊洛沙姆以及能够赋予溶液正/负电荷特性的多肽相结合,利用特定结构的多肽的选择及其正/负电荷的控制,可以赋予羊膜凝胶材料具备良好的温度敏感性,具有良好的应用前景。
(2)本发明所述材料具有良好的温度敏感性,表现在:在常温(25℃)下具有良好的流动性及可注射性;在35~43℃下能够快速(10s至1min)从流动态液体转变为不具流动性的固体凝胶,因此,可以延长羊膜凝胶材料在创面靶向区域的驻留时间,提高其作用效果。
(3)基于本发明所述材料的温度敏感性能,可实现在眼科、骨科、神经外科手术中作为羊膜水凝胶使用,并具有良好的应用前景。
具体实施方式
下面将本发明的发明目的、技术方案和有益效果作进一步详细的说明。
应该指出,以下详细说明都是示例性的,旨在对所要求的本发明提供进一步的说明,除非另有说明,本文使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解的相同含义。
本发明旨在提供一种温度敏感性羊膜凝胶材料及其制备方法和应用,该羊膜凝胶材料因具有在常温下呈流体并具有良好的可注射性,在接近人体温度下快速形成凝胶状的性能而具备本发明所述的温度敏感性,适用于眼科、骨科或神经外科手术中作为羊膜水凝胶使用,在临床应用中,通过将羊膜水凝胶注射到人体创面后,在接近人体温度引发下,能够快速形成凝胶状而避免流动到其他非靶向区域,由此可延长其在创面靶向区域的驻留时间,提高羊膜的组织再生修复作用。
本发明提供的温度敏感性羊膜凝胶材料主要由羊膜冻干粉末、卡波姆、泊洛沙姆、正电荷特性多肽、负电荷特性多肽和生理盐水组成,各组分的质量百分浓度控制在羊膜冻干粉末0.1~5wt%、卡波姆0.1~5wt%、泊洛沙姆20~35wt%、正电荷特性多肽1~10wt%、负电荷特性多肽1~10wt%,其余为生理盐水。
其中,羊膜冻干粉末是以羊膜为原料,经清洗、晾干、冰浴粉碎、离心及滤纸抽滤获得羊膜提取物后,再经冷冻干燥而制得。其制备步骤具体如下:
步骤(a):清洗:将预先冷冻(-20℃)的新鲜羊膜从冰箱取出,将其包材喷洒75%酒精进行消毒,放入车间传递窗进料口进行紫外杀菌30min。将羊膜取出进行拆袋,用镊子将羊膜取出放入304托盘或烧杯中,加入纯化水没过羊膜大于2cm。5min后初步解冻用手将羊膜分散,避免团缩。每隔30min换水一次,每次将羊膜进行翻面且进行轻轻搅拌,去除其表面残留杂质。重复此步骤至少3次,直至加入纯化水后溶液依旧保持澄清。
步骤(b):晾干:清洗干净的羊膜用手将其取出,放在筛网上晾干,底部放上托盘接住其脱离的水分。羊膜需进行铺平,如无法进行铺平将其裁剪分割,羊膜不能叠加放置。晾干时羊膜需15min进行一次翻面,共晾干1h。
步骤(c):冰浴粉碎并冷冻干燥:用准备好的烧杯放入电子天平进行归零,用烧杯将羊膜盛装好后进行称量,记录其湿重。将准备好的纯化水冰块(1cm×1cm×1cm~3cm×3cm×3cm)进行称量,与羊膜的质量比为1∶1~5∶1,随后将冰块倒入烧杯中。将冰水羊膜混合液放入实验粉碎机静置5分钟后进行粉碎(等待部分冰块融化),同时用冰袋包裹物料杯控制粉碎过程中料液温度<8℃,每次粉碎10~60S设备休息1min,重复此过程共30~90次即粉碎完成,得到羊膜提取物。
步骤(d):冷冻干燥:将羊膜提取物置于冷冻干燥机中,保持-30℃低温干燥48小时,即得。
正电荷特性多肽的氨基酸序列为RRHKHRR(Arg-Arg-His-Lys-His-Arg-Arg),其结构式如下式(1)所示;负电荷特性多肽的氨基酸序列为DDDKEEE(Asp-Asp-Asp-Lys-Glu-Glu-Glu),其结构式如下式(2)所示。
(1)
(2)
本发明中,通过控制正电荷特性多肽的电荷量为5~10mV,负电荷特性多肽的电荷量为-10~-5mV,实现所制备的羊膜凝胶材料在35~43℃下能够快速(10s至1min)从流动态液体转变为不具流动性的固体凝胶。
本发明中,通过控制正电荷特性多肽及负电荷特性多肽的用量即可控制对应溶液电荷量的大小。
此外,本发明中卡波姆的作用是调节凝胶的粘度,泊洛沙姆的作用是进一步增强材料的温敏敏感特性,优选的泊洛沙姆为泊洛沙姆407。
为制备得到本发明所述的羊膜凝胶材料,首先,取上述方法制备得到的羊膜冻干粉末,配制成0.1~5wt%的羊膜冻干粉末的水溶液,将卡波姆0.1~5wt%、泊洛沙姆407为20~35wt%以及1~10wt%的正电荷特性多肽加入到该羊膜冻干粉末的水溶液中,即得组分A。然后,配制1~10wt%的负电荷特性多肽的水溶液,即得组分B。最后,将组分A和组分B装入到双管道混合注射器中,密封后经过辐照灭菌,置于常温保存,即得温度敏感性羊膜凝胶材料。
下面结合实施例对本发明作进一步地详细说明,但本发明的实施方式不限于此。
以下实施方式中,正电荷特性多肽(氨基酸序列为RRHKHRR)及负电荷特性多肽氨基酸序列为DDDKEEE)均来自于上海强耀生物科技有限公司。卡波姆和泊洛沙姆407可通过市售渠道购买获得。
实施例1:羊膜冻干粉末
本实施例涉及羊膜冻干粉末的制备方法,包括如下步骤:
步骤(a):清洗:将预先冷冻(-20℃)的新鲜人源羊膜从冰箱取出,将其包材喷洒75%酒精进行消毒,放入车间传递窗进料口进行紫外杀菌30min。将羊膜取出进行拆袋,用镊子将羊膜取出放入304托盘或烧杯中,加入纯化水没过羊膜大于2cm。5min后初步解冻用手将羊膜分散,避免团缩。每隔30min换水一次,每次将羊膜进行翻面且进行轻轻搅拌,去除其表面残留杂质。重复此步骤至少3次,直至加入纯化水后溶液依旧保持澄清。
步骤(b):晾干:清洗干净的羊膜用手将其取出,放在筛网上晾干,底部放上托盘接住其脱离的水分。羊膜需进行铺平,如无法进行铺平将其裁剪分割,羊膜不能叠加放置。晾干时羊膜需15min进行一次翻面,共晾干1h。
步骤(c):冰浴粉碎并冷冻干燥:用准备好的烧杯放入电子天平进行归零,用烧杯将羊膜盛装好后进行称量,记录其湿重。将准备好的纯化水冰块(1cm×1cm×1cm)进行称量,与羊膜的质量比为1:1,随后将冰块倒入烧杯中。将冰水羊膜混合液放入实验粉碎机静置5分钟后进行粉碎(等待部分冰块融化),同时用冰袋包裹物料杯控制粉碎过程中料液温度<8℃,每次粉碎10S设备休息1min,重复此过程共30次即粉碎完成,得到羊膜提取物。
步骤(d):冷冻干燥:将羊膜提取物置于冷冻干燥机中,保持-30℃低温干燥48小时,即得。
实施例2:温度敏感性羊膜凝胶材料
本实施例涉及的温度敏感性羊膜凝胶材料中包含以下浓度的组份:0.1wt%的羊膜冻干粉末、0.1wt%的卡波姆981、20wt%的泊洛沙姆407、1wt%的正电荷特性多肽、1wt%的负电荷特性多肽以及生理盐水,其中,正电荷特性多肽的氨基酸序列为RRHKHRR,负电荷特性多肽的氨基酸序列为DDDKEEE。
其制备方法步骤如下:
(1)将实施例1制备的羊膜冻干粉末配制成为0.1wt%(质量百分浓度,所述浓度均为最终材料折算后的浓度)的生理盐水溶液;
(2)将0.1wt%的卡波姆981、20wt%的泊洛沙姆407、1wt%的正电荷特性多肽加入到步骤(1)的羊膜冻干粉末的生理盐水溶液中,即得组分A;
(3)配制1wt%的负电荷特性多肽水溶液,即为组分B;
(4)将组分A和组分B装入到双管道混合注射器中,密封后经过辐照灭菌,置于常温保存。
实施例3:温度敏感性羊膜凝胶材料
本实施例涉及的温度敏感性羊膜凝胶材料中包含以下浓度的组份:0.5wt%的羊膜冻干粉末、0.3wt%的卡波姆981、30wt%的泊洛沙姆407、5wt%的正电荷特性多肽、5wt%的负电荷特性多肽及生理盐水,其中,正电荷特性多肽和负电荷特性多肽以及凝胶材料的制备方法均同实施例2。
实施例4:温度敏感性羊膜凝胶材料
本实施例涉及的温度敏感性羊膜凝胶材料中包含以下浓度的组份:2wt%的羊膜冻干粉末、5wt%的卡波姆981、35wt%的泊洛沙姆407、10wt%的正电荷特性多肽、10wt%的负电荷特性多肽及生理盐水,其中,正电荷特性多肽和负电荷特性多肽以及凝胶材料的制备方法均同实施例2。
实施例5:温度敏感性羊膜凝胶材料
本实施例涉及的温度敏感性羊膜凝胶材料中包含以下浓度的组份:5wt%的羊膜冻干粉末、5wt%的卡波姆981、35wt%的泊洛沙姆407、10wt%的正电荷特性多肽、10wt%的负电荷特性多肽及生理盐水,其中,正电荷特性多肽和负电荷特性多肽以及凝胶材料的制备方法均同实施例2。
对比例1:
将实施例1制备的羊膜冻干粉末配制成为0.5wt%的生理盐水溶液。
对比例2:
将实施例1制备的羊膜冻干粉末配制成为0.5wt%的生理盐水溶液,并加入0.3wt%的卡波姆981。
对比例3:
将实施例1制备的羊膜冻干粉末配制成为0.5wt%的生理盐水溶液,并加入30wt%的泊洛沙姆407。
对比例4:
将实施例1制备的羊膜冻干粉末配制成为0.5wt%的生理盐水溶液,并加入0.3wt%的卡波姆以及30wt%的泊洛沙姆407。
对比例5:
按实施例2的相同制备方法制得,含有以下浓度的组分:0.5wt%的羊膜冻干粉末、0.3wt%的卡波姆981、30wt%的泊洛沙姆407、0.1wt%的正电荷特性多肽、0.1wt%的负电荷特性多肽及生理盐水,其中,正电荷特性多肽和负电荷特性多肽以及材料的制备方法均同实施例2。
对比例6:
按实施例2的相同制备方法制得,含有以下浓度的组分:0.5wt%的羊膜冻干粉末、0.3wt%的卡波姆981、30wt%的泊洛沙姆407、20wt%的正电荷特性多肽、20wt%的负电荷特性多肽及生理盐水。其中,正电荷特性多肽和负电荷特性多肽以及材料的制备方法均同实施例2。
测试例1:成胶固化测试
测试样品:实施例2至实施例5,对比例1至对比例6制备的材料。
测试方法:将材料置于37℃恒温箱,观察并记录平均成胶固化时间。
测试结果如下表1所示。
表1
37℃下平均成胶固化时间 | |
实施例2 | 1min |
实施例3 | 30s |
实施例4 | 10s |
实施例5 | 10s |
对比例1 | 无法成胶固化 |
对比例2 | 无法成胶固化 |
对比例3 | 8min |
对比例4 | 8min |
对比例5 | 大于10min仍未成胶固化 |
对比例6 | 小于1s瞬时成胶固化 |
从表1结果可知,实施例2至实施例5制备的羊膜凝胶材料在37℃下平均成胶固化时间为10s~1min。对比例1为仅含有羊膜冻干粉末的悬液,无法成胶固化。对比例2为含有羊膜冻干粉末的悬液中添加卡波姆的材料,无法成胶固化。对比例3为羊膜冻干粉末的悬液中添加泊洛沙姆407的材料,固化时间较长,为约8分钟。对比例4为羊膜冻干粉末的悬液中添加卡波姆以及泊洛沙姆407的材料,固化时间较长,为约8分钟。对比例5为使用过低浓度多肽制备的材料,大于10min仍未成胶固化。对比例6为使用过高浓度多肽制备的材料,小于1s瞬时成胶固化。可见,材料组成中正负电荷多肽浓度直接决定其成胶固化时间。
测试例2 :表面电位测试
测试样品:实施例2至实施例5以及对比例5、对比例6中使用的正电荷特性多肽及负电荷特性多肽水溶液。
测试方法:采用SurPass3 表面电位分析仪(Anton Paar有限公司,奥地利)进行表面电位分析。
测试结果如下表2所示。
表2
正电荷特性多肽浓度(wt%) | 表面电位数值(mV) | 负电荷特性多肽浓度(wt%) | 表面电位数值(mV) | |
实施例2 | 1 | 5.4 | 1 | -5.3 |
实施例3 | 5 | 7.4 | 5 | -7.3 |
实施例4 | 10 | 9.8 | 10 | -9.7 |
实施例5 | 10 | 9.8 | 10 | -9.7 |
对比例5 | 0.1 | 1.2 | 0.1 | -1.1 |
对比例6 | 20 | 42.5 | 20 | -41.2 |
从表2结果可知,实施例2至实施例5中使用的正电荷特性多肽中的正电荷电位为:5~10 mV,负电荷特性多肽中的负电荷电位为:-10~-5mV,且多肽水溶液的平均表面电位与其使用浓度直接相关。
测试例3:创面驻留时间测试
测试样品:实施例2至实施例5以及对比例1中制备的材料。
测试方法:首先对材料采用荧光素进行标记,步骤如下:将异硫氰酸荧光素(FITC)溶于二甲基亚砜(DMSO)中,浓度为20mg/mL。称量样品,按照(样品:FITC)=1mg:150μg的比例将FITC缓慢加入于样品中,边加边轻轻晃动使其混合均匀,避光4℃反应8h。加入5M的NH4Cl至终浓度50mM,4℃终止反应2h。将标记产物在PBS中透析4次以上,至透析液清亮。
取新西兰兔(2±0.5kg)采用戊巴比妥钠静脉注射麻醉后,眼球向上侧身固定,用剃须刀去除眼部周围绒毛和睫毛,用碘伏进行消毒处理;用奥布卡因对眼表进行局部麻醉。将实施例及对比例中制备的荧光素标记的材料施加到兔眼球表面,每两小时一次,持续三次;第二天,将新西兰兔安乐死后取出眼球,随后将兔眼球放入匀浆机中提取水溶性物质,采用酶标仪对490nm激发波长、520nm发射波长的荧光进行定量检测。
测试结果如下表3所示。
表3
荧光强度(490nm/520nm) | |
实施例2 | 2.14 |
实施例3 | 3.15 |
实施例4 | 5.23 |
实施例5 | 7.35 |
对比例1 | 0.11 |
从表3结果可知,实施例2至实施例5中羊膜凝胶相比于对比例1中的仅含有羊膜冻干粉末的悬液,FITC的荧光强度有大幅提升,即反映其创面驻留时间有效延长。
应用例:羊膜凝胶在眼科手术中的应用
建立动物模型:取50只新西兰兔(2±0.5kg)采用戊巴比妥钠静脉注射麻醉后,右眼向上侧身固定,用剃须刀去除右眼周围绒毛和睫毛,用碘伏进行消毒处理。用奥布卡因对眼表进行局部麻醉,干滤纸吸去角膜上多余水分,用浸润了浓度为1mol/L的H2SO4溶液的直径约6 mm的单层圆形滤纸,贴附于角膜中央区域表面,计时30秒除去滤纸。用干滤纸吸去角膜上多余酸液后用大量生理盐水冲洗 5 min。造模一周后观察创面愈合情况,去除烧伤较轻已自愈和过重烧伤角膜全层的模型,取中轻度烧伤。自身修复能力不能使创面愈合的40个模型用于修复实验。
手术方法:手术操作均使用无菌手术器械,严格按照临床手术要求进行。
(1)羊膜实验组
每组随机取8只烧伤模型(2±0.5kg)采用戊巴比妥钠静脉注射麻醉后,前后肢用绳子固定,手术洞巾包裹实验兔全身,用电动剃须刀将兔右眼周围绒毛去除干净,用碘伏进行消毒处理,尽量减少对手术过程和后期角膜修复的影响。手术部位为角膜酸烧伤模型创面区域,在显微镜下首先对受损部位进行清创,用宝石刀将坏死的角膜上皮、组织彻底清理干净。取实施例2至实施例5制备的羊膜凝胶,涂覆于眼表创面部位,每两小时一次,每天3次,持续3天。
(2)空白对照组
取其余8只烧伤模型,手术方法与实验组手术方法相同,不使用羊膜凝胶,其余操作及后期护理与实验组相同。
术后评价:观察并拍照记录如下评价项目:每天观察实验兔子的精神状态及活动情况、观察角膜修复情况。动物实验评价标准:整体观察角膜修复后的形态。按照下表分类对动物实验中角膜的修复情况进行评价,如下表4所示。
表4
项目 | 0级 | 1级 | 2级 | 3级 | 4级 |
角膜上皮缺损面积S(荧光素钠) | 无着色 | S≤1/4角膜 | 1/4角膜<S ≤1/2角膜 | 1/2角膜<S ≤3/4角膜 | 3/4角膜<S |
(参考全国眼外伤职业眼病学组的分度标准,以及Roper—Hall对眼部化学损伤程度的分级)
采用上述“动物实验评价标准”评价方法,于8周对空白对照组和羊膜实验组进行荧光素钠染色,观察角膜上皮缺损面积。评估生物羊膜修复眼表的安全性和有效性。
结果分析:参见术后上皮化评分结果,如下表5所示。
表5
从表5结果可知,采用实施例2至实施例5制备的羊膜凝胶实验组术后角膜上皮缺损面积较小,即上皮化明显由优于空白组。
以上所述,仅是本发明的较佳实施例,并非对本发明做任何形式上的限制,凡是依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化,均落入本发明的保护范围之内。
Claims (7)
1.一种温度敏感性羊膜凝胶材料,其特征在于:包含以下浓度的组份:羊膜冻干粉末0.1~5wt%、卡波姆0 .1~5wt%、泊洛沙姆20~35wt%、正电荷特性多肽1~10wt%、负电荷特性多肽1~10wt%,其余为生理盐水,
所述正电荷特性多肽的氨基酸序列为RRHKHRR,其电荷量为5~10mV,该正电荷特性多肽的结构式如下式(1)所示:
(1);
所述负电荷特性多肽的氨基酸序列为DDDKEEE,其电荷量为-10~-5mV,该负电荷特性多肽的结构式如下式(2)所示:
(2)。
2.根据权利要求1所述的温度敏感性羊膜凝胶材料,其特征在于:所述羊膜冻干粉末是以羊膜为原料,经清洗、晾干、冰浴粉碎获得羊膜提取物后,再经冷冻干燥而制得。
3.根据权利要求2所述的温度敏感性羊膜凝胶材料,其特征在于:所述冰浴粉碎是将晾干后的羊膜与冰块混合形成冰水羊膜混合液后再进行粉碎的过程,其中将冰块与羊膜混合时,控制冰块与羊膜的质量比为1∶1~5∶1。
4.根据权利要求3所述的温度敏感性羊膜凝胶材料,其特征在于:所述粉碎时,每次粉碎10~60S,停止1min,重复此过程30~90次。
5.如权利要求1~4任一项所述温度敏感性羊膜凝胶材料的制备方法,其特征在于:按配比,配制羊膜冻干粉末的水溶液,将卡波姆、泊洛沙姆以及正电荷特性多肽加入到羊膜冻干粉末的水溶液中,即得组分A;配制负电荷特性多肽的水溶液,即得组分B;将组分A和组分B混合后,即得。
6.如权利要求1~5任一项所述温度敏感性羊膜凝胶材料在制备医用材料中的应用,其特征在于:所述医用材料包括眼科、骨科或神经外科手术用羊膜水凝胶。
7.根据权利要求6所述的应用,其特征在于:所述羊膜水凝胶在常温下为流体,在35~43℃下,于10s~1min内从流体转变固态。
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