CN112999410A - 含全氟萘烷的纳米氧合水凝胶促愈合敷料及其制法和用途 - Google Patents
含全氟萘烷的纳米氧合水凝胶促愈合敷料及其制法和用途 Download PDFInfo
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Abstract
本发明提供了一种纳米氧合水凝胶促愈合敷料的制备方法，包括如下步骤：a、先将乳化剂加入到部分PBS缓冲溶液中，再加入全氟萘烷超声，制备得到纳米乳液；b、将上述纳米乳液先中压均质和高压均质循环，得到纳米粒；c、将上述纳米粒分装至西林瓶中，同时加入冻干保护剂，再将其进行冻干，制得冻干粉末；d、将透明质酸钠溶于剩余PBS缓冲溶液中，再加入步骤c得到的冻干粉末，即得含全氟萘烷的纳米氧合水凝胶促愈合敷料。本发明水凝胶敷料中含有的全氟萘烷具有强溶解氧的能力和良好的保湿透气性。涂抹于创面后，可隔绝创面和外环境，使伤口不接触环境中的病原体，有利于保持创面的持续供氧环境，加快上皮再生，安全性高。
Description
技术领域
本发明属于水凝胶技术领域，具体地涉及一种含全氟萘烷的纳米氧合水凝胶促愈合敷料及其制法和用途。
背景技术
随着人口逐渐老年化和糖尿病患者增加，慢性伤口已成为全球医疗领域面临的一个重大挑战；糖尿病是一种广泛的疾病，全世界有4亿多人患有糖尿病，到2040年，糖尿病患者人数预计将超过6.4亿。糖尿病的并发症，特别是慢性未愈合伤口对生活质量产生破坏性影响，并大幅增加社会医疗费用。严重的是，全世界截肢中约70％的截肢是由糖尿病足溃疡引起的，而近年来仍缺乏持续有效的治疗方法。糖尿病难以愈合的创面主要由创面组织氧合较低、微血管闭塞、高糖环境下细菌定植和周围神经病变引起。
其中，局部创面缺氧被认为是造成创面愈合不良的一个重要原因。氧在人体能量生产中起着不可或缺的作用，可通过需氧糖酵解产生三磷酸腺苷。在伤口愈合过程中，足够的氧合更为重要，因为胶原蛋白合成、攻击细菌和细胞增殖等修复过程可能需要充足的能量。然而，糖尿病慢性伤口由于血管损伤、血管通透性和高代谢需求，供氧严重不足。在坏死区，组织氧通常小于10mmHg(而正常组织为约40mmHg)。现有的方法无论是高压氧治疗还是局部氧治疗(TOT)都难以缓解伤口缺氧。受损的血管限制了血液中的氧在循环中的扩散，组织的紧密性限制了气体中的氧渗透到伤口中。在这些病例中，我们提出了局部溶解氧(TDO)治疗方案，旨在将部分高压氧注入湿愈合过程中，以改善氧在组织中的渗透和吸收。但该方法仍依赖于高压氧发生器，使用不便，使创面存在感染风险。
为了创造一种局部输送溶解氧的方法，研究表明，全氟萘烷是一种安全性很高的化合物，常温下为无色、无味、无毒的透明液体,密度高,表面张力低,化学性质稳定,在体内不发生代谢。尤为重要的是,全氟萘烷具有良好的气体运载能力,对氧的溶解度约为水的20倍,是全血的2～3倍,二氧化碳的溶解度是水的3倍多，100毫升的全氟萘烷能溶氧气50毫升，是红细胞载氧能力的1.5倍；全氟萘烷和氧的结合速度是14-20毫秒，比红细胞快得多；由此可见，全氟化碳是较理想的氧载体，且具有创伤修复、抗菌性、抗氧化性、消炎等作用。全氟萘烷有良好的组织相容性和生物学上的惰性，早已在生物医用领域得到应用，但是由于全氟萘烷难溶于水，稳定性差，生物利用率低等特性，使其在创面敷料上的应用具有较大的困难。
因此，目前急需一种可以主动供氧且工艺简单的水凝胶敷料，为伤口提供富氧环境，解决创面细胞因缺氧而愈合缓慢的问题。
发明内容
本发明的目的是为了解决现有技术中存在的缺点，提供了一种具有良好的力学性能，柔韧性和弹性好，能够与皮肤形成良好粘合，可解决慢性伤口局部缺氧等问题的纳米氧合水凝胶促愈合敷料。
本发明采用的技术方案为：一种含全氟萘烷的纳米氧合水凝胶促愈合敷料，按重量份数计，包括以下组分：透明质酸钠1-3份、PBS缓冲溶液150-250份、全氟萘烷1-10份、冻干保护剂1-20份和乳化剂1-20份。
优选的，按重量份数计，包括以下组分：透明质酸钠2份、PBS缓冲溶液200份、全氟萘烷5份、冻干保护剂10份和乳化剂10份。
优选的，所述乳化剂为酪蛋白、泊洛沙姆、吐温、白蛋白、磷脂及其衍生物中的任意一种，所述冻干保护剂为葡萄糖、甘露醇或氨基酸中的任意一种。
纳米氧合水凝胶促愈合敷料的制备方法，包括如下步骤：a、先将乳化剂加入到部分PBS缓冲溶液中，再加入全氟萘烷超声，制备得到纳米乳液；
b、将上述纳米乳液先中压均质10～30个循环，再高压均质25～70个循环，均质压力110Mpa，得到纳米粒；
c、将上述纳米粒分装至西林瓶中，同时加入冻干保护剂，再将其进行冻干，制得冻干粉末；
d、将透明质酸钠溶于剩余PBS缓冲溶液中，再加入步骤c得到的冻干粉末，即得含全氟萘烷的纳米氧合水凝胶促愈合敷料。
优选的，所述步骤a中超声的功率为300-500W，超声总时间为10～16min，2min/次，共5～8次，冰浴控温，每次超声间相隔两分钟降温。
优选的，所述步骤c中冻干的具体过程为：将冻干机在-40℃条件下预冻2～4小时，再抽真空，样品冻干后将真空度恢复至大气压，然后迅速取出杨平加塞压盖，制得冻干粉末。
含全氟萘烷的纳米氧合水凝胶促愈合敷料的用途，所述敷料中的全氟萘烷可通过析氧提高伤口表面的氧气浓度和湿度，可应用于慢性伤口、外伤、烧伤、烫伤、溃疡或褥疮伤口。
优选的，所述敷料可应用于糖尿病足慢性伤口。
优选的，所述敷料适用于手肘、手腕、膝盖或脚腕的经常性活动部位的伤口。
本发明获得的有益效果为：本发明的全氟萘烷纳米氧合水凝胶敷料，白色粘稠，是一种兼具加速愈合和安全性的新型智能水凝胶创面敷料，可应用于慢性伤口、外伤、烧伤、烫伤、溃疡、褥疮等伤口，尤其是如糖尿病足式的慢性伤口效果更佳。
(1)本发明水凝胶敷料中含有的全氟萘烷具有强溶解氧的能力和良好的保湿透气性。涂抹于创面后，可隔绝创面和外环境，使伤口不接触环境中的病原体，有利于保持创面的持续供氧环境，加快上皮再生，安全性高；通过析氧可以有效提高伤口表面的氧气浓度和湿度，氧浓度的提高直接增效伤口愈合，湿度的提高有利于气体在伤口表面渗透扩散，以及通过湿性愈合的方式促进创面愈合。
(2)本发明选用的乳化剂不仅具有良好的湿润分散性，能与全氟萘烷乳化分散在水凝胶之中，并且能够给人体提供一个营养供给，增加血容量和维持一个血浆的胶体渗透压。使其能够稳定存在，克服了全氟萘烷不溶于水、稳定性差的缺点，从而在涂抹伤口时能够缓慢地释放氧气。
(3)本发明选用的冻干保护剂呈多孔状、能长时间稳定储存，并且重新复水而恢复活性。
(4)本发明采用乳化和冻干模板法制备全氟萘烷水凝胶敷料；先将乳化剂与全氟萘烷乳化，使用冻干保护剂低温冻干成粉末，最终在透明质酸钠凝胶中复溶，克服了全氟萘烷无法分散、慢性伤口局部缺氧等问题，原料来源广泛、价格便宜，成本可控，可实现工业化生产。
(5)本发明的全氟萘烷纳米氧合水凝胶敷料具有良好的力学性能，柔韧性和弹性好，能够与皮肤形成良好粘合，并且全氟萘烷分散其中可以保持稳定，不易破乳、团聚和沉降。适用于身体不同部位的创面，特别是手肘、手腕、膝盖、脚腕等经常性活动部位。
附图说明
图1为本发明纳米氧合水凝胶敷料的治疗原理图；
图2为透明质酸钠凝胶形状图；
图3为含有乳化剂的凝胶形状图；
图4为含有冻干保护剂的凝胶形状图；
图5为本发明全氟萘烷纳米氧合水凝胶形状图；
图6为本发明水凝胶样品标尺为200纳米的电镜图；
图7为慢性创面动物实验—伤口愈合进展图；
图8为慢性创面动物实验—伤口肉芽组织愈合对照实验图；
图9为慢性创面动物实验—伤口愈合时间对照实验图；
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。
实施例1：一种含有全氟萘烷的纳米氧合水凝胶促愈合敷料，按重量份数计，包括以下组分：透明质酸钠2份、PBS缓冲溶液200份、全氟萘烷2份、氨基酸5份、白蛋白3份。
水凝胶促愈合敷料的制备方法，包括如下步骤：a、先将乳化剂加入100份PBS缓冲溶液中，再加入全氟萘烷超声制备纳米乳液。功率为300w，超声总时间为12min，2min/次，共6次，乳化过程冰浴控温，每次乳化间，相隔两分钟降温。b、然后将初乳先中压均质20个循环，再高压均质50个循环，均质压力110Mpa；c、冻干过程：将纳米粒分装至3mL西林瓶中，每瓶1mL，同时加入冻干保护剂，将样品置于冻干机中在-40℃条件下预冻3小时，再抽真空，样品冻干后将真空度恢复至大气压，然后迅速取出样品加塞压盖，制得冻干粉末。d、将透明质酸钠溶于100份PBS缓冲溶液中，再加入步骤c得到的冻干粉末，即得含全氟萘烷的纳米氧合水凝胶促愈合敷料。
实施例2：一种含有全氟萘烷的纳米氧合水凝胶促愈合敷料，按重量份数计，包括以下组分：透明质酸钠3份、PBS缓冲溶液200份、全氟萘烷1份、甘露醇6份、酪蛋白5份。
水凝胶促愈合敷料的制备方法，包括如下步骤：a、先将乳化剂加入100份PBS缓冲溶液中，再加入全氟萘烷超声制备纳米乳液。功率为500w，超声总时间为12min，2min/次，共6次，乳化过程冰浴控温，每次乳化间，相隔两分钟降温。b、然后将初乳先中压均质20个循环，再高压均质50个循环，均质压力110Mpa；c、冻干过程：将纳米粒分装至3mL西林瓶中，每瓶1mL，同时加入冻干保护剂，将样品置于冻干机中在-40℃条件下预冻3小时，再抽真空，样品冻干后将真空度恢复至大气压，然后迅速取出样品加塞压盖，制得冻干粉末。d、将透明质酸钠溶于100份PBS缓冲溶液中，再加入步骤c得到的冻干粉末，即得含全氟萘烷的纳米氧合水凝胶促愈合敷料。
实施例3：一种含有全氟萘烷的纳米氧合水凝胶促愈合敷料，按重量份数计，包括以下组分：透明质酸钠2份、PBS缓冲溶液200份、全氟萘烷3份、葡萄糖溶液10份、酪蛋白4份。
水凝胶促愈合敷料的制备方法，包括如下步骤：a、先将乳化剂加入100份PBS缓冲溶液中，再加入全氟萘烷超声制备纳米乳液。功率为400w，超声总时间为12min，2min/次，共6次，乳化过程冰浴控温，每次乳化间，相隔两分钟降温。b、然后将初乳先中压均质20个循环，再高压均质50个循环，均质压力110Mpa；c、冻干过程：将纳米粒分装至3mL西林瓶中，每瓶1mL，同时加入冻干保护剂，将样品置于冻干机中在-40℃条件下预冻3小时，再抽真空，样品冻干后将真空度恢复至大气压，然后迅速取出样品加塞压盖，制得冻干粉末。d、将透明质酸钠溶于100份PBS缓冲溶液中，再加入步骤c得到的冻干粉末，即得含全氟萘烷的纳米氧合水凝胶促愈合敷料。
以实施例3为例对本发明全氟萘烷纳米氧合水凝胶敷料的性状进行测试
正常组为非糖尿病组且自然愈合；糖尿病组为患糖尿病的小鼠且自然愈合；凝胶组为患糖尿病小鼠且伤口涂覆不含全氟萘烷凝胶的敷料；全氟纳米氧合凝胶组为患糖尿病小鼠且伤口涂覆本发明实施例3含全氟萘烷凝胶的敷料。
对照水凝胶促愈合敷料的动物实验方法，包括如下步骤：a、先养老鼠适应环境7天，饲料为高脂高糖造出糖尿病小鼠模型；b、在老鼠背部剪出直径1cm左右的伤口，涂上水凝胶敷料与对照组试剂；c、每天准时换药，与空白对照、不含全氟萘烷水凝胶组进行对照，准时测量伤口长度并记录，制得伤口愈合柱状图，如图8-9所示，老鼠背部伤口愈合表面情况如图7所示。
实验表明，本发明敷料的伤口愈合速度明显优于无含全氟萘烷凝胶品及自然愈合的速度。
以上所述，仅为本发明较佳的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，根据本发明的技术方案及其发明构思加以等同替换或改变，都应涵盖在本发明的保护范围之内。
Claims (9)
1.一种含全氟萘烷的纳米氧合水凝胶促愈合敷料，其特征在于：按重量份数计，包括以下组分：透明质酸钠1-3份、PBS缓冲溶液150-250份、全氟萘烷1-10份、冻干保护剂1-20份和乳化剂1-20份。
2.根据权利要求1所述一种含全氟萘烷的纳米氧合水凝胶促愈合敷料，其特征在于：按重量份数计，包括以下组分：透明质酸钠2份、PBS缓冲溶液200份、全氟萘烷5份、冻干保护剂10份和乳化剂10份。
3.根据权利要求1或2所述一种含全氟萘烷的纳米氧合水凝胶促愈合敷料，其特征在于：所述乳化剂为酪蛋白、泊洛沙姆、吐温、白蛋白、磷脂及其衍生物中的任意一种，所述冻干保护剂为葡萄糖、甘露醇或氨基酸中的任意一种。
4.纳米氧合水凝胶促愈合敷料的制备方法，其特征在于：包括如下步骤：a、先将乳化剂加入到部分PBS缓冲溶液中，再加入全氟萘烷超声，制备得到纳米乳液；
b、将上述纳米乳液先中压均质10～30个循环，再高压均质25～70个循环，均质压力110Mpa，得到纳米粒；
c、将上述纳米粒分装至西林瓶中，同时加入冻干保护剂，再将其进行冻干，制得冻干粉末；
d、将透明质酸钠溶于剩余PBS缓冲溶液中，再加入步骤c得到的冻干粉末，即得含全氟萘烷的纳米氧合水凝胶促愈合敷料。
5.根据权利要求4上述纳米氧合水凝胶促愈合敷料的制备方法，其特征在于：所述步骤a中超声的功率为300-500W，超声总时间为10～16min，2min/次，共5～8次，冰浴控温，每次超声间相隔两分钟降温。
6.根据权利要求4上述纳米氧合水凝胶促愈合敷料的制备方法，其特征在于：所述步骤c中冻干的具体过程为：将冻干机在-40℃条件下预冻2～4小时，再抽真空，样品冻干后将真空度恢复至大气压，然后迅速取出杨平加塞压盖，制得冻干粉末。
7.含全氟萘烷的纳米氧合水凝胶促愈合敷料的用途，其特征在于：所述敷料中的全氟萘烷可通过析氧提高伤口表面的氧气浓度和湿度，可应用于慢性伤口、外伤、烧伤、烫伤、溃疡或褥疮伤口。
8.根据权利要求7所述含全氟萘烷的纳米氧合水凝胶促愈合敷料的用途，其特征在于：所述敷料可应用于糖尿病足慢性伤口。
9.根据权利要求7或8所述含全氟萘烷的纳米氧合水凝胶促愈合敷料的用途，其特征在于：所述敷料适用于手肘、手腕、膝盖或脚腕的经常性活动部位的伤口。
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