CN112301496A - 可控降解手术缝合线的制备方法 - Google Patents
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Abstract
本发明涉及可控降解手术缝合线的制备方法，包括如下步骤：基于α‑I胶原(GENEANK NUMBER:GB_NM_000088.4)蛋白序列与蛋白酶酶切识别序列使用分子生物学技术设计一种可控降解重组胶原蛋白基因；使用生物发酵技术表达重组胶原蛋白；分离纯化重组胶原蛋白，并制备可控降解手术缝合线。通过本方法制备的手术缝合线力学性能达到了临床应用的要求，且能在伤口组织愈合的合适时期实现缝合线的迅速降解，降解的缝合线能被人体吸收，具有更好的应用前景。
Description
技术领域
本发明涉及手术缝合线技术领域，具体是可控降解手术缝合线的制备方法。
背景技术
手术缝合线是指在外科手术当中，用于伤口结扎缝合止血以及组织缝合的一种特殊用线。根据其生物降解性能可分为两类：不可吸收线和可吸收线。
其中不可吸收线具有拉力强度高、易于消毒灭菌、组织反应低的特点，但是不能在体内降解，术后拆线带来二次疼痛和感染以及留下疤痕；
而可吸收线在体内可以降解成为可溶性产物，被人体吸收并逐步排泄出体外，从而减轻了病人痛苦。
目前，医学界常用的可吸收缝合线多为纯天然胶原蛋白缝合线(如羊肠线)和化学合成线。
例如中国发明专明专利“几丁聚糖可吸收医用缝合线及其制作方法”(公开号CN1586635)公开了一种几丁聚糖手术缝合线的制备方法；哺乳动物神经纤维可吸收缝合线的制取制作方法(公开号CN1879898)公开了一种从成年脊椎哺乳类啮齿动物取尾部的神经纤维分离可吸收手术缝合线的方法。
在具体实践中发现，纯天然胶原蛋白缝合线大多存在柔韧性欠佳，组织反应大，制品规格不易控制的缺点，植入体内后在消化液或感染环境中会发生强度变化，还有发生机体免疫反应的可能。而化学合成可吸收缝合线缺点在于：降解的产物偏酸性，在使用部位产生不同程度的肿胀，产生“无菌性积液”现象，即非特性无菌性炎症现象，需要及时排出肿胀部位里的液体才可肿胀消除，增加了对病人术后护理的难度，延缓了伤口愈合的速度。
发明内容
本发明所要解决的技术问题是提供可控降解手术缝合线的制备方法，以解决现有技术中存在的缺陷。
本发明解决上述技术问题的技术方案如下：
可控降解手术缝合线的制备方法，包括以下步骤：
S1基于α-I胶原(GENEANK NUMBER:GB_NM_000088.4)蛋白序列与蛋白酶酶切识别序列使用分子生物学技术设计一种可控降解重组胶原蛋白基因；
S2使用生物发酵技术表达重组胶原蛋白；
S3分离纯化重组胶原蛋白，并制备可控降解手术缝合线。
进一步的，步骤S2中，所述胶原蛋白的分子量大于0.9×106；
进一步的，步骤S3中，可控降解手术缝合线采用湿纺工艺技术制备；
进一步的，步骤S1中制备的重组胶原蛋白的氨基酸序列为：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。
本发明的有益效果是：通过本方法制备的手术缝合线力学性能达到了临床应用的要求，且能在伤口组织愈合的合适时期实现缝合线的迅速降解，降解的缝合线能被人体吸收，具有更好的应用前景。
附图说明
图1为本发明结构示意图；
具体实施方式
以下结合附图对本发明的原理和特征进行描述，所举实例只用于解释本发明，并非用于限定本发明的范围。
如图1所示，可控降解手术缝合线的制备方法，包括以下步骤：
S1基于α-I胶原(GENEANK NUMBER:GB_NM_000088.4)蛋白序列与蛋白酶酶切识别序列使用分子生物学技术设计一种可控降解重组胶原蛋白基因；
S2使用生物发酵技术表达重组胶原蛋白；
S3分离纯化重组胶原蛋白，并制备可控降解手术缝合线。
其中步骤S1中制备的重组胶原蛋白的氨基酸序列为：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。
具体实施例1
可控降解手术缝合线的制备方法，包括以下步骤：
S1基于α-I胶原(GENEANK NUMBER:GB_NM_000088.4)蛋白序列与蛋白酶酶切识别序列使用分子生物学技术设计一种可控降解重组胶原蛋白基因；
S2使用生物发酵技术表达重组分子量大于0.9×106的胶原蛋白；
S3分离纯化重组胶原蛋白，并制备可控降解手术缝合线。
其中步骤S1中制备的重组胶原蛋白的氨基酸序列为：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。
具体实施例2
可控降解手术缝合线的制备方法，包括以下步骤：
S1基于α-I胶原(GENEANK NUMBER:GB_NM_000088.4)蛋白序列与蛋白酶酶切识别序列使用分子生物学技术设计一种可控降解重组胶原蛋白基因；
S2使用生物发酵技术表达重组胶原蛋白；
S3分离纯化重组胶原蛋白，采用湿纺工艺技术制备可控降解手术缝合线。
其中步骤S1中制备的重组胶原蛋白的氨基酸序列为：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。
具体实施例3
S1基于α-I胶原(GENEANK NUMBER:GB_NM_000088.4)蛋白序列与蛋白酶酶切识别序列使用分子生物学技术设计一种可控降解重组胶原蛋白基因；
S2使用生物发酵技术表达重组分子量大于0.9×106的胶原蛋白；
S3分离纯化重组胶原蛋白，采用湿纺工艺技术制备可控降解手术缝合线。
其中步骤S1中制备的重组胶原蛋白的氨基酸序列为：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。
本发明具有如下优点：
通过本方法制备的手术缝合线力学性能达到了临床应用的要求，且能在伤口组织愈合的合适时期实现缝合线的迅速降解，降解的缝合线能被人体吸收，具有更好的应用前景。
以上所述仅为本发明的较佳实施例，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、改进等，均应包含在本发明的保护范围之内。
Claims (4)
1.可控降解手术缝合线的制备方法，其特征在于，包括以下步骤：
S1基于α-I胶原(GENEANK NUMBER:GB_NM_000088.4)蛋白序列与蛋白酶酶切识别序列使用分子生物学技术设计一种可控降解重组胶原蛋白基因；
S2使用生物发酵技术表达重组胶原蛋白；
S3分离纯化重组胶原蛋白，并制备可控降解手术缝合线。
2.根据权利要求1所述的可控降解手术缝合线的制备方法，其特征在于：步骤S2中，所述胶原蛋白的分子量大于0.9×106。
3.根据权利要求2所述的可控降解手术缝合线的制备方法，其特征在于：步骤S3中，可控降解手术缝合线采用湿纺工艺技术制备。
4.根据权利要求1所述的可控降解手术缝合线的制备方法，其特征在于：步骤S1中制备的重组胶原蛋白的氨基酸序列为：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。
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