CN113248743A - 一种生物相容的可降解的三维纤维素凝胶及其制备方法和应用 - Google Patents

一种生物相容的可降解的三维纤维素凝胶及其制备方法和应用 Download PDF

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CN113248743A
CN113248743A CN202110681102.4A CN202110681102A CN113248743A CN 113248743 A CN113248743 A CN 113248743A CN 202110681102 A CN202110681102 A CN 202110681102A CN 113248743 A CN113248743 A CN 113248743A
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薛宏
田平
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Jiaxing Yingsheng Biology Co ltd
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Abstract

本发明涉及生物材料技术领域，具体涉及一种生物相容的可降解的三维纤维素凝胶及其制备方法和应用。本发明以完全食品级的羧甲基纤维素钠、聚乙二醇和柠檬酸作为原料，通过物理的热干蒸法，制得了一种生物兼容性好的三维纤维素凝胶，并且由于羧甲基纤维素钠和聚乙二醇杂化纳米结构的形成，制得一种以纤维素为基础的复合材料，生物相容的可降解的三维纤维素凝胶能够被广泛应用在食品添加剂、生物医疗材料、细胞基质中。

Description

一种生物相容的可降解的三维纤维素凝胶及其制备方法和 应用
技术领域
本发明涉及生物材料技术领域，具体涉及一种生物相容的可降解三维纤维素凝胶及其制备方法和应用。
背景技术
高分子凝胶是分子链经交联聚合而成的三维网络或互穿网络与溶剂(通常是水)组成的体系。高分子凝胶的制备和应用发展比较迅速，其具有很多优点，如吸水性、环境敏感性、保水性、生物相容性等使其备受关注。目前化学交联凝胶是凝胶的一个主要种类，化学交联凝胶是高分子链段间以共价键的形式交联而成的，具有结构稳定性较好，制备相对容易等优点，但是它们具有不能生物降解和生物兼容性差的缺陷，使其在生物医疗领域的应用受到了限制，因此具有生物兼容性的凝胶材料越来越受到生物医疗产业的关注。
植物纤维素是地球上最丰富的可再生资源，羧甲基纤维素是纤维素的一种衍生物，和纤维素一样同属于环境友好材料，纤维素及其衍生物因其来源丰富、可用性强等优点，可被用来制备凝胶，但传统方法制备的凝胶存在一些缺点，例如制得的凝胶机械性能差、溶胀率低等，目前使用的生物兼容性好的凝胶材料其力学性能没法达到生物材料使用的要求。
发明内容
针对上述存在的技术不足，本发明提供了一种生物相容的可降解的三维纤维素凝胶及其制备方法和应用，本发明以完全食品级的羧甲基纤维素钠、聚乙二醇和柠檬酸作为原料，通过物理的热干蒸法，制得了一种生物兼容性好的三维纤维素凝胶，并且由于羧甲基纤维素钠和聚乙二醇杂化纳米结构的形成，制得一种以纤维素为基础的复合材料，生物相容的可降解的三维纤维素凝胶能够被广泛应用在食品添加剂、生物医疗材料、细胞基质中。
为实现上述目的，本发明的技术方案如下：
一种生物相容的可降解三维纤维素凝胶的制备方法，包括以下步骤：
步骤1、搅拌条件下，将羧甲基纤维素钠溶解于蒸馏水中制得羧甲基纤维素钠溶液，向羧甲基纤维素钠溶液中加入聚乙二醇并混合均匀，继续加入柠檬酸，并搅拌1-8h，制得混合液；
其中，羧甲基纤维素钠溶液中羧甲基纤维素钠与水的质量比为2-6：100；
羧甲基纤维素钠与聚乙二醇的质量比为10-50:1；
羧甲基纤维素钠和聚乙二醇总干重与柠檬酸的质量比为1：0.01-0.1；
步骤2、将步骤1的混合液于40-50℃下干燥至水分蒸发完全，然后于80-120℃交联6-24h，制得凝胶；
步骤3、采用蒸馏水浸泡和洗涤步骤2的凝胶，制得生物相容的可降解三维纤维素凝胶。
优选的，所述羧甲基纤维素钠选自取代度为0.7-1.2的食用级或医用级的羧甲基纤维素，其分子量250kDa，粘度500-2000。
优选的，所述聚乙二醇选自分子量为1500-2000的食用级聚乙二醇或医用级聚乙二醇。
优选的，所述步骤2中或所述步骤3中还设置有定型过程；
所述步骤2中定型过程为：将步骤1的混合液倒入至模具中然后于40-50℃下干燥至水分蒸发完全；
所述步骤3中定型过程为：将洗涤后的凝胶倒入至模具中然后干燥至水分小于0.1wt％。
优选的，所述步骤3中浸泡和洗涤的方法为：将步骤2的凝胶加入至蒸馏水中，蒸馏水与凝胶的质量比为50-100:1，每次洗涤4-6h。
本发明还保护了制备方法制得的生物相容的可降解三维纤维素凝胶。
本发明还保护了生物相容的可降解三维纤维素凝胶在制备食品添加剂、生物医疗材料或药物中的应用。
优选的，所述生物相容的可降解三维纤维素凝胶用于制备饱腹感添加剂。
优选的，所述生物相容的可降解三维纤维素凝胶用于制备糖尿病足敷料或细胞基质或组织工程基质。
优选的，所述生物相容的可降解三维纤维素凝胶用于制备药物控释剂。
本发明的有益效果：
1、本发明使用物理热干蒸法，通过加热过程中原料分子间的静电作用、链缠绕、氢键等作用而形成的交联反应，本发明研究表明：聚乙二醇在杂化聚合物网络结构的形成中起着重要作用，这也是凝胶具有优异的力学性能的主要原因。
2、本发明以完全食品级的羧甲基纤维素钠(CMA)、聚乙二醇(PEG)和柠檬酸(CA)作为原料，通过物理的热干蒸法制备了一种生物兼容性好的三维纤维素凝胶，并且由于羧甲基纤维素钠和聚乙二醇杂化纳米结构的形成，提升表面纳米力学性能，制得了一种弹性模量达到1000-2000MPa的凝胶，制得了生物兼容性好、力学性能达到生物材料使用要求的凝胶材料。
3、本发明制得的凝胶对人胚胎肾细胞表现出了良好的细胞兼容性，其可广泛应用在生物医疗材料、组织工程基质中；本发明的凝胶在体外与人胚胎肾细胞共同培养24小时后，细胞依然有平均97±2.1％的细胞活性(根据ISO10993-5-2009/(R)2014，医疗器械的生物评价：体外细胞毒性试验测定)。
附图说明
图1为本发明生物相容的可降解三维纤维素凝胶的物理交联反应示意图；
图2为本发明实施例2制得的生物相容的可降解三维纤维素凝胶的实物图；
图3为本发明实施例2制得的生物相容的可降解三维纤维素凝胶与对比例1及对比例2的材料的弹性模量对照图；
图4为本发明实施例2制得的生物相容的可降解三维纤维素凝胶的医疗器械生物评价对照图。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合附图及实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
下述实验方法和检测方法，如没有特殊说明，均为常规方法；下述试剂和原料，如没有特殊说明，均为市售。
实施例1
一种生物相容的可降解三维纤维素凝胶的制备方法，包括以下步骤：
步骤1、搅拌条件下，将2g羧甲基纤维素钠溶解于100mL蒸馏水中形成羧甲基纤维素钠溶液，向羧甲基纤维素钠溶液中加入0.2g聚乙二醇并混合均匀，继续加入0.22g柠檬酸，并搅拌1h，制得混合液；
所述羧甲基纤维素钠选自取代度为0.7-1.2的食用级或医用级的羧甲基纤维素，其分子量250kDa，粘度500-2000；
所述聚乙二醇选自分子量为1500-2000的食用级聚乙二醇或医用级聚乙二醇；
步骤2、将步骤1的混合液于40℃下干燥至水分蒸发完全，蒸发掉表面液体，然后于120℃交联6h，制得凝胶；
步骤3、采用蒸馏水浸泡和洗涤步骤2的凝胶，蒸馏水与凝胶的质量比为50:1，每次洗涤6h，制得生物相容的可降解三维纤维素凝胶。
实施例2
一种生物相容的可降解三维纤维素凝胶的制备方法，包括以下步骤：
步骤1、搅拌条件下，将4g羧甲基纤维素钠溶解于100mL蒸馏水中形成羧甲基纤维素钠溶液，向羧甲基纤维素钠溶液中加入0.08g聚乙二醇并混合均匀，继续加入0.2g柠檬酸，并搅拌5h，制得混合液；
所述羧甲基纤维素钠选自取代度为0.7-1.2的食用级或医用级的羧甲基纤维素，其分子量250kDa，粘度500-2000；
所述聚乙二醇选自分子量为1500-2000的食用级聚乙二醇或医用级聚乙二醇；
步骤2、将步骤1的混合液于45℃下干燥至水分蒸发完全，蒸发掉表面液体，然后于100℃交联16h，制得凝胶；
步骤3、采用蒸馏水浸泡和洗涤步骤2的凝胶，蒸馏水与凝胶的质量比为75:1，每次洗涤5h，制得生物相容的可降解三维纤维素凝胶(CMC+8％w/wPEG+5％w/wCA)。
实施例3
一种生物相容的可降解三维纤维素凝胶的制备方法，包括以下步骤：
步骤1、搅拌条件下，将6g羧甲基纤维素钠溶解于100mL蒸馏水中形成羧甲基纤维素钠溶液，向羧甲基纤维素钠溶液中加入0.12g聚乙二醇并混合均匀，继续加入0.06g柠檬酸，并搅拌8h，制得混合液；
所述羧甲基纤维素钠选自取代度为0.7-1.2的食用级或医用级的羧甲基纤维素，其分子量250kDa，粘度500-2000；
所述聚乙二醇选自分子量为1500-2000的食用级聚乙二醇或医用级聚乙二醇；
步骤2、将步骤1的混合液于50℃下干燥至水分蒸发完全，蒸发掉表面液体，然后于80℃交联24h，制得凝胶；
步骤3、采用蒸馏水浸泡和洗涤步骤2的凝胶，蒸馏水与凝胶的质量比为100:1，每次洗涤4h，制得生物相容的可降解三维纤维素凝胶。
对比例1
与实施例2的制备步骤相同，不同之处仅在于，不添加柠檬酸。(CMC+8％w/wPEG)
对比例2
实施例1-3及对比例1使用的市售的羧甲基纤维素钠(CMC)。
下面对本发明制得的生物相容的可降解三维纤维素凝胶进行性能研究，实施例1-3制得的生物相容的可降解三维纤维素凝胶性能相近，下面以实施例2为例，具体研究结果如图1-4所示：
图1为生物相容的可降解三维纤维素凝胶的物理交联反应示意图，由示意图能够看出，在使用物理热干蒸法后，通过加热过程中原料分子间的静电作用、链缠绕、氢键等作用而形成了交联反应，制得了三维纤维素凝胶。
图2为可降解三维纤维素凝胶的实物图，图2说明了本申请制得了可降解三维纤维素凝胶。
图3中对实施例2、对比例1及对比例2的样品进行了弹性模量的对比和分析，结果表明聚乙二醇(PEG)是本发明产物刚性(弹性模量测量)重要的影响因素；且结果也表明了本申请制得的生物相容的可降解三维纤维素凝胶的弹性模量能够达到1000-2000MPa，具有优异的力学性能。
图4为依据ISO 10993-5-2009(医疗器械的生物评价：体外细胞毒性试验测定)中的MTT室验，检测了本发明的材料的细胞毒性。其基本过程为：将人胚胎肾细胞接种于96孔培养板中，培养24小时，形成至细胞单层铺满孔底，然后分别将其暴露在不同材料中，所述材料为实施例1的凝胶、对比例1的凝胶，其中阴性对照为曲拉通X-100，阳性对照为培养基；暴露24小时后，对于每个处理，计算生长抑制的百分比，其结果表明：本发明制得的生物相容的可降解三维纤维素凝胶材料良好的细胞兼容性。
以上仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。
显然，本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样，倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内，则本发明也意图包含这些改动和变型在内。

Claims (10)

1.一种生物相容的可降解三维纤维素凝胶的制备方法，其特征在于，包括以下步骤：
步骤1、搅拌条件下，将羧甲基纤维素钠溶解于蒸馏水中制得羧甲基纤维素钠溶液，向羧甲基纤维素钠溶液中加入聚乙二醇并混合均匀，继续加入柠檬酸，并搅拌1-8h，制得混合液；
其中，羧甲基纤维素钠溶液中羧甲基纤维素钠与水的质量比为2-6：100；
羧甲基纤维素钠与聚乙二醇的质量比为10-50:1；
羧甲基纤维素钠和聚乙二醇总干重与柠檬酸的质量比为1：0.01-0.1；
步骤2、将步骤1的混合液于40-50℃下干燥至水分蒸发完全，然后于80-120℃交联6-24h，制得凝胶；
步骤3、采用蒸馏水浸泡和洗涤步骤2的凝胶，制得生物相容的可降解三维纤维素凝胶。
2.根据权利要求1所述的一种生物相容的可降解三维纤维素凝胶的制备方法，其特征在于，所述羧甲基纤维素钠选自取代度为0.7-1.2的食用级或医用级的羧甲基纤维素，其分子量250kDa，粘度500-2000。
3.根据权利要求1所述的一种生物相容的可降解三维纤维素凝胶的制备方法，其特征在于，所述聚乙二醇选自分子量为1500-2000的食用级聚乙二醇或医用级聚乙二醇。
4.根据权利要求1所述的一种生物相容的可降解三维纤维素凝胶的制备方法，其特征在于，所述步骤2中或所述步骤3中还设置有定型过程；
所述步骤2中定型过程为：将步骤1的混合液倒入至模具中然后于40-50℃下干燥至水分蒸发完全；
所述步骤3中定型过程为：将洗涤后的凝胶倒入至模具中然后干燥至水分小于0.1wt％。
5.根据权利要求1所述的一种生物相容的可降解三维纤维素凝胶的制备方法，其特征在于，所述步骤3中浸泡和洗涤的方法为：将步骤2的凝胶加入至蒸馏水中，蒸馏水与凝胶的质量比为50-100:1，每次洗涤4-6h。
6.一种权利要求1-5任一项所述制备方法制得的生物相容的可降解三维纤维素凝胶。
7.一种权利要求6所述的生物相容的可降解三维纤维素凝胶在制备食品添加剂、生物医疗材料或药物中的应用。
8.根据权利要求7所述的应用，其特征在于，所述生物相容的可降解三维纤维素凝胶用于制备饱腹感添加剂。
9.根据权利要求7所述的应用，其特征在于，所述生物相容的可降解三维纤维素凝胶用于制备糖尿病足敷料或细胞基质或组织工程基质。
10.根据权利要求7所述的应用，其特征在于，所述生物相容的可降解三维纤维素凝胶用于制备药物控释剂。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114573836A (zh) * 2022-03-07 2022-06-03 北京海步医药科技有限公司 水凝胶及其生产方法
CN114702734A (zh) * 2022-04-08 2022-07-05 重庆师范大学 一种纤维素醚类凝胶及其制备方法和应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101128488A (zh) * 2004-12-29 2008-02-20 路易吉·安布罗西奥 可生物降解的超吸收性聚合物水凝胶及其制备方法
CN104327307A (zh) * 2014-10-29 2015-02-04 广州纤维产品检测研究院 一种纤维素类的可生物降解水凝胶的制备方法
US20180333428A1 (en) * 2017-04-14 2018-11-22 Gelesis Llc Compositions and methods for treating or preventing gut permeability-related disorders
US20190015564A1 (en) * 2017-07-14 2019-01-17 Soonchunhyang University Industry Academy Cooperation Foundation Adhesion prevention agent comprising injectable thermosensitive wood based-oxidized cellulose nanofiber
CN112341672A (zh) * 2020-10-22 2021-02-09 爱美客技术发展股份有限公司 一种修饰的交联羧甲基纤维素凝胶及其制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101128488A (zh) * 2004-12-29 2008-02-20 路易吉·安布罗西奥 可生物降解的超吸收性聚合物水凝胶及其制备方法
CN104327307A (zh) * 2014-10-29 2015-02-04 广州纤维产品检测研究院 一种纤维素类的可生物降解水凝胶的制备方法
US20180333428A1 (en) * 2017-04-14 2018-11-22 Gelesis Llc Compositions and methods for treating or preventing gut permeability-related disorders
US20190015564A1 (en) * 2017-07-14 2019-01-17 Soonchunhyang University Industry Academy Cooperation Foundation Adhesion prevention agent comprising injectable thermosensitive wood based-oxidized cellulose nanofiber
CN112341672A (zh) * 2020-10-22 2021-02-09 爱美客技术发展股份有限公司 一种修饰的交联羧甲基纤维素凝胶及其制备方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114573836A (zh) * 2022-03-07 2022-06-03 北京海步医药科技有限公司 水凝胶及其生产方法
CN114573836B (zh) * 2022-03-07 2024-04-12 北京海步医药科技有限公司 水凝胶及其生产方法
CN114702734A (zh) * 2022-04-08 2022-07-05 重庆师范大学 一种纤维素醚类凝胶及其制备方法和应用

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