CN113018419B - 一种创面修复和抑制瘢痕的医用几丁糖纳米微球及其制备方法 - Google Patents
一种创面修复和抑制瘢痕的医用几丁糖纳米微球及其制备方法 Download PDFInfo
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Abstract
本发明涉及医药领域,具体为一种创面修复和抑制瘢痕的医用几丁糖纳米微球,还涉及一种创面修复和抑制瘢痕的医用几丁糖纳米微球的制备方法,针对现有医用几丁糖纳米微球创面修复治疗不佳、不能抑制瘢痕、载药量低、分散性差以及纳米微球颗粒的尺寸不稳定的问题,现如今提出如下方案:包括以下重量份的原料:壳聚糖3~6份、1%醋酸溶液4~8份、乙醇1~2份、人参皂苷Rg3 0.1~0.2份、多巴胺0.4~0.5份、BFGF 0.1~0.2份、乳化剂4~6份、液体石蜡20~32份、交联剂12~18份。本发明制得的医用几丁糖纳米微球增强了创面修复治疗效果且可抑制瘢痕的形成,同时,具有载药量高和分散性好的优点,医用几丁糖纳米微球颗粒的尺寸稳定。
Description
技术领域
本发明涉及医药领域,具体为一种创面修复和抑制瘢痕的医用几丁糖纳米微球,还涉及一种创面修复和抑制瘢痕的医用几丁糖纳米微球的制备方法。
背景技术
纳米微球材料具有优异的生物相容性和可调的生物降解性,可用于药物、蛋白和基因的包埋和释放,相较于频繁注射给药,采用纳米微球载药实现药物在体内的缓慢释放,达到理想的治疗效果,其中,医用几丁糖纳米微球是由蟹壳提纯的高分子化合物几丁质,经脱N-乙酰基再深加工后制得得一种聚氨基葡萄糖,具有选择性促进上皮细胞和内皮细胞生长而抑制成纤维细胞生长的生物特性,可促进组织生理性修复,是组织工程和再生医学领域常用的医用材料。
现有医用几丁糖纳米微球不能在初期促进皮肤再生和快速修复,后期抑制成纤维细胞过度增生,导致不能抑制增生性瘢痕的生成,制备得到的医用几丁糖纳米微球促进损伤皮肤组织的修复和愈合伤疤作用力度低,影响创面修复治疗效果,壳聚糖在酸性环境下发生降解,导致水相溶液的黏度降低,使得经该方法制备得到的医用几丁糖纳米微球载药量低,分散性差,医用几丁糖纳米微球颗粒的尺寸不稳定。
发明内容
(一)解决的技术问题
针对上述背景技术提出的不足,本发明提供了一种创面修复和抑制瘢痕的医用几丁糖纳米微球及其制备方法,解决了上述背景技术提出的问题。
(二)技术方案
为实现上述目的,本发明提供如下技术方案:
一种创面修复和抑制瘢痕的医用几丁糖纳米微球,包括以下重量份的原料:壳聚糖3~6份、1%醋酸溶液4~8份、乙醇1~2份、人参皂苷Rg3 0.1~0.2份、多巴胺0.4~0.5份、BFGF 0.1~0.2份、乳化剂4~6份、液体石蜡20~32份、交联剂12~18份。
优选的,包括以下重量份的原料:壳聚糖4~6份、1%醋酸溶液5~8份、乙醇1~2份、人参皂苷Rg3 0.15~0.2份、多巴胺0.4~0.5份、BFGF 0.15~0.2份、乳化剂5~6份、液体石蜡22~32份、交联剂14~18份。
优选的,包括以下重量份的原料:壳聚糖5份、1%醋酸溶液6份、乙醇1份、人参皂苷Rg3 0.15份、多巴胺0.4份、BFGF 0.15份、乳化剂4份、液体石蜡26份、交联剂14份。
优选的,所述人参皂苷Rg3和BFGF的重量份配比为1:1。
优选的,所述乳化剂选用山梨醇酐倍半油酸酯或单硬脂酸甘油酯。
优选的,所述交联剂选用京尼平或香草醛缩丙酮。
本发明还提供一种创面修复和抑制瘢痕的医用几丁糖纳米微球的制备方法,包括以下步骤:
S1油相体系的制备:量取定量液体石蜡缓慢加入圆底烧瓶中,加入定量乳化剂,搅拌圆底烧瓶中的液体直至混匀,形成油相体系,得到油相,备用;
S2水相体系的制备:量取定量壳聚糖溶于定量1%醋酸溶液中,后取定量乙醇加入,使用超声搅拌器搅拌1h,形成水相体系,得到水相,备用;
S3乳浊液的制备:使用1mL移液器吸取水相,缓慢多次的滴加到油相中,离心搅拌20~30min,离心条件为500~1000rpm,得到乳状油包水乳浊液;
S4搅拌:在乳浊液中缓慢加入定量人参皂苷Rg3、多巴胺和BFGF,用超声波搅拌器充分搅拌1~1.5h,后加入交联剂,搅拌混匀;
S5离心分离:将经步骤S4处理后的乳浊液倒入离心管中,经离心机进行离心处理25min;
S6一次洗涤:向离心管中加入15mL石油醚洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置6~8min,吸除分层后的上清液;
S7二次洗涤:向经步骤S6处理后的离心管中加入15mL丙酮洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置6~8min;
S8干燥保存:吸除经步骤S7处理分层后的上清液,冷冻干燥后得到医用几丁糖纳米微球,收集并置于干燥环境下保存。
(三)有益效果
与现有技术相比,本发明提供了一种创面修复和抑制瘢痕的医用几丁糖纳米微球及其制备方法,具备以下有益效果:
人参皂苷Rg3浸于多巴胺水溶液中,使得表面自聚一层聚多巴胺,作为桥梁,配合掺入BFGF到纤维表面,使得医用几丁糖纳米微球载有抑制增生性瘢痕的微纳米纤维支架,在初期促进皮肤再生和快速修复,后期抑制成纤维细胞过度增生而有效抑制增生性瘢痕的生成,制备得到的医用几丁糖纳米微球具有促进损伤皮肤组织的修复和愈合伤疤作用,增强创面修复治疗效果。
掺入乙醇使得水相在制备时,通过抑制壳聚糖在酸性环境下的降解以延缓水相溶液黏度的降低速率,使得经该方法制备得到的医用几丁糖纳米微球具有载药量高和分散性好的优点,配合掺入交联剂,使得医用几丁糖纳米微球颗粒的尺寸稳定。
综上,本发明掺入人参皂苷Rg3浸于多巴胺水溶液中,使得表面自聚一层聚多巴胺,作为桥梁,配合掺入BFGF到纤维表面,使得医用几丁糖纳米微球载有抑制增生性瘢痕的微纳米纤维支架,在初期促进皮肤再生和快速修复,后期抑制成纤维细胞过度增生而有效抑制增生性瘢痕的生成,制备得到的医用几丁糖纳米微球具有促进损伤皮肤组织的修复和愈合伤疤作用,增强创面修复治疗效果;掺入乙醇使得水相在制备时,通过抑制壳聚糖在酸性环境下的降解以延缓水相溶液黏度的降低速率,使得经该方法制备得到的医用几丁糖纳米微球具有载药量高和分散性好的优点,配合掺入交联剂,使得医用几丁糖纳米微球颗粒的尺寸稳定。
具体实施方式
下面将结合本发明的实施例,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,基于本发明中的实施例,本领域普通技术人员在没有做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。
实施例一:
一种创面修复和抑制瘢痕的医用几丁糖纳米微球,包括以下重量份的原料:壳聚糖3份、1%醋酸溶液4份、乙醇1份、人参皂苷Rg3 0.1份、多巴胺0.4份、BFGF 0.1份、山梨醇酐倍半油酸酯4份、液体石蜡20份、京尼平12份。
一种创面修复和抑制瘢痕的医用几丁糖纳米微球的制备方法,包括以下步骤:
S1油相体系的制备:量取20份液体石蜡缓慢加入圆底烧瓶中,加入4份山梨醇酐倍半油酸酯,搅拌圆底烧瓶中的液体直至混匀,形成油相体系,得到油相,备用;
S2水相体系的制备:量取3份壳聚糖溶于4份的1%醋酸溶液中,后取1份乙醇加入,使用超声搅拌器搅拌1h,形成水相体系,得到水相,备用;
S3乳浊液的制备:使用1mL移液器吸取水相,缓慢多次的滴加到油相中,离心搅拌20min,离心条件为1000rpm,得到乳状油包水乳浊液;
S4搅拌:在乳浊液中缓慢加入0.1份人参皂苷Rg3、0.4份多巴胺和0.1份BFGF,用超声波搅拌器充分搅拌1h,后加入12份京尼平,搅拌混匀;
S5离心分离:将经步骤S4处理后的乳浊液倒入离心管中,经离心机进行离心处理25min;
S6一次洗涤:向离心管中加入15mL石油醚洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置6min,吸除分层后的上清液;
S7二次洗涤:向经步骤S6处理后的离心管中加入15mL丙酮洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置6min;
S8干燥保存:吸除经步骤S7处理分层后的上清液,冷冻干燥后得到医用几丁糖纳米微球,收集并置于干燥环境下保存。
实施例二:
一种创面修复和抑制瘢痕的医用几丁糖纳米微球,包括以下重量份的原料:壳聚糖4份、1%醋酸溶液7份、乙醇2份、人参皂苷Rg3 0.2份、多巴胺0.4份、BFGF 0.2份、单硬脂酸甘油酯6份、液体石蜡30份、京尼平16份。
一种创面修复和抑制瘢痕的医用几丁糖纳米微球的制备方法,包括以下步骤:
S1油相体系的制备:量取30份液体石蜡缓慢加入圆底烧瓶中,加入6份单硬脂酸甘油酯,搅拌圆底烧瓶中的液体直至混匀,形成油相体系,得到油相,备用;
S2水相体系的制备:量取4份壳聚糖溶于7份的1%醋酸溶液中,后取2份乙醇加入,使用超声搅拌器搅拌1h,形成水相体系,得到水相,备用;
S3乳浊液的制备:使用1mL移液器吸取水相,缓慢多次的滴加到油相中,离心搅拌25min,离心条件为700rpm,得到乳状油包水乳浊液;
S4搅拌:在乳浊液中缓慢加入0.2份人参皂苷Rg3、0.4份多巴胺和0.2份BFGF,用超声波搅拌器充分搅拌1.2h,后加入16份京尼平,搅拌混匀;
S5离心分离:将经步骤S4处理后的乳浊液倒入离心管中,经离心机进行离心处理25min;
S6一次洗涤:向离心管中加入15mL石油醚洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置7min,吸除分层后的上清液;
S7二次洗涤:向经步骤S6处理后的离心管中加入15mL丙酮洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置6min;
S8干燥保存:吸除经步骤S7处理分层后的上清液,冷冻干燥后得到医用几丁糖纳米微球,收集并置于干燥环境下保存。
实施例一和实施例二中,通过人参皂苷Rg3浸于多巴胺水溶液中,使得表面自聚一层聚多巴胺,作为桥梁,配合掺入BFGF到纤维表面,使得医用几丁糖纳米微球载有抑制增生性瘢痕的微纳米纤维支架,在初期促进皮肤再生和快速修复,后期抑制成纤维细胞过度增生而有效抑制增生性瘢痕的生成,制备得到的医用几丁糖纳米微球具有促进损伤皮肤组织的修复和愈合伤疤作用,增强创面修复治疗效果;掺入乙醇使得水相在制备时,通过抑制壳聚糖在酸性环境下的降解以延缓水相溶液黏度的降低速率,使得经该方法制备得到的医用几丁糖纳米微球具有载药量高和分散性好的优点,配合掺入交联剂,使得医用几丁糖纳米微球颗粒的尺寸稳定。
实施例三:
一种创面修复和抑制瘢痕的医用几丁糖纳米微球,包括以下重量份的原料:壳聚糖5份、1%醋酸溶液6份、乙醇1份、人参皂苷Rg3 0.15份、多巴胺0.4份、BFGF 0.15份、山梨醇酐倍半油酸酯4份、液体石蜡26份、香草醛缩丙酮14份、可降解医用聚氨酯8份、促进伤口愈合的高分子材料4份、具有生物抗炎活性的小分子药物4份。
优选的,所述可降解医用聚氨酯优选聚酯型PU(包括以PCL、GA为软段并以赖氨酸二异氰酸酯为硬段的降解时间在7~14天的PU材料、用赖氨酸二异氰酸酯交联多聚赖氨酸的PU材料、天然高分子羧甲基纤维素或透明质酸为软段并以赖氨酸二异氰酸酯为硬段的PU材料)、聚乙交酯、聚丙交酯与聚乙交酯的共聚物、聚己内酯-乙交酯以及聚赖氨酸中的一种或两种组合。
所述高分子材料为透明质酸钠、透明质酸锌、海藻酸盐、改性海藻酸盐及其降解成氨基己糖和N-乙酰氨基葡萄糖的海藻酸盐中的一种或两种组合。
所述小分子药物为多肽类、氨基酸以及各种抗炎药物的一种或两种组合。
一种创面修复和抑制瘢痕的医用几丁糖纳米微球的制备方法,包括以下步骤:
S1油相体系的制备:量取26份液体石蜡缓慢加入圆底烧瓶中,加入4份山梨醇酐倍半油酸酯,搅拌圆底烧瓶中的液体直至混匀,形成油相体系,得到油相,备用;
S2水相体系的制备:量取5份壳聚糖溶于6份的1%醋酸溶液中,后取1份乙醇加入,使用超声搅拌器搅拌1h,形成水相体系,得到水相,备用;
S3乳浊液的制备:使用1mL移液器吸取水相,缓慢多次的滴加到油相中,离心搅拌27min,离心条件为850rpm,得到乳状油包水乳浊液;
S4搅拌:在乳浊液中缓慢加入0.15份人参皂苷Rg3、0.4份多巴胺、0.15份BFGF、8份可降解医用聚氨酯、4份促进伤口愈合的高分子材料和4份具有生物抗炎活性的小分子药物,用超声波搅拌器充分搅拌1.2h,后加入14份香草醛缩丙酮,搅拌混匀;
S5离心分离:将经步骤S4处理后的乳浊液倒入离心管中,经离心机进行离心处理25min;
S6一次洗涤:向离心管中加入15mL石油醚洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置7min,吸除分层后的上清液;
S7二次洗涤:向经步骤S6处理后的离心管中加入15mL丙酮洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置7min;
S8干燥保存:吸除经步骤S7处理分层后的上清液,冷冻干燥后得到医用几丁糖纳米微球,收集并置于干燥环境下保存。
实施例四
一种创面修复和抑制瘢痕的医用几丁糖纳米微球,包括以下重量份的原料:壳聚糖6份、1%醋酸溶液8份、乙醇2份、人参皂苷Rg3 0.2份、多巴胺0.5份、BFGF0.2份、单硬脂酸甘油酯6份、液体石蜡32份、香草醛缩丙酮18份、可降解医用聚氨酯10份、促进伤口愈合的高分子材料4份、具有生物抗炎活性的小分子药物5份。
优选的,所述可降解医用聚氨酯优选聚酯型PU(包括以PCL、GA为软段并以赖氨酸二异氰酸酯为硬段的降解时间在7~14天的PU材料、用赖氨酸二异氰酸酯交联多聚赖氨酸的PU材料、天然高分子羧甲基纤维素或透明质酸为软段并以赖氨酸二异氰酸酯为硬段的PU材料)、聚乙交酯、聚丙交酯与聚乙交酯的共聚物、聚己内酯-乙交酯以及聚赖氨酸中的一种或两种组合。
所述高分子材料为透明质酸钠、透明质酸锌、海藻酸盐、改性海藻酸盐及其降解成氨基己糖和N-乙酰氨基葡萄糖的海藻酸盐中的一种或两种组合。
所述小分子药物为多肽类、氨基酸以及各种抗炎药物的一种或两种组合。
一种创面修复和抑制瘢痕的医用几丁糖纳米微球的制备方法,包括以下步骤:
S1油相体系的制备:量取32份液体石蜡缓慢加入圆底烧瓶中,加入6份单硬脂酸甘油酯,搅拌圆底烧瓶中的液体直至混匀,形成油相体系,得到油相,备用;
S2水相体系的制备:量取6份壳聚糖溶于8份的1%醋酸溶液中,后取2份乙醇加入,使用超声搅拌器搅拌1h,形成水相体系,得到水相,备用;
S3乳浊液的制备:使用1mL移液器吸取水相,缓慢多次的滴加到油相中,离心搅拌30min,离心条件为500rpm,得到乳状油包水乳浊液;
S4搅拌:在乳浊液中缓慢加入0.2份人参皂苷Rg3、0.5份多巴胺、0.2份BFGF、10份可降解医用聚氨酯、4份促进伤口愈合的高分子材料、5份具有生物抗炎活性的小分子药物,用超声波搅拌器充分搅拌1.5h,后加入18份香草醛缩丙酮,搅拌混匀;
S5离心分离:将经步骤S4处理后的乳浊液倒入离心管中,经离心机进行离心处理25min;
S6一次洗涤:向离心管中加入15mL石油醚洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置8min,吸除分层后的上清液;
S7二次洗涤:向经步骤S6处理后的离心管中加入15mL丙酮洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置7min;
S8干燥保存:吸除经步骤S7处理分层后的上清液,冷冻干燥后得到医用几丁糖纳米微球,收集并置于干燥环境下保存。
实施例三和实施例四中,人参皂苷Rg3浸于多巴胺水溶液中,使得表面自聚一层聚多巴胺,作为桥梁,配合掺入BFGF到纤维表面,使得医用几丁糖纳米微球载有抑制增生性瘢痕的微纳米纤维支架,在初期促进皮肤再生和快速修复,后期抑制成纤维细胞过度增生而有效抑制增生性瘢痕的生成,制备得到的医用几丁糖纳米微球具有促进损伤皮肤组织的修复和愈合伤疤作用,增强创面修复治疗效果;掺入乙醇使得水相在制备时,通过抑制壳聚糖在酸性环境下的降解以延缓水相溶液黏度的降低速率,使得经该方法制备得到的医用几丁糖纳米微球具有载药量高和分散性好的优点,配合掺入交联剂,使得医用几丁糖纳米微球颗粒的尺寸稳定。
尽管已经示出和描述了本发明的实施例,对于本领域的普通技术人员而言,可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型,本发明的范围由所附权利要求及其等同物限定。
Claims (1)
1.一种创面修复和抑制瘢痕的医用几丁糖纳米微球,其特征在于,由以下重量份的原料组成:壳聚糖5份、1%醋酸溶液6份、乙醇1份、人参皂苷Rg30.15份、多巴胺0.4份、BFGF0.15份、乳化剂4份、液体石蜡26份、交联剂14份;
所述乳化剂选用山梨醇酐倍半油酸酯或单硬脂酸甘油酯;
所述交联剂选用京尼平或香草醛缩丙酮;
所述创面修复和抑制瘢痕的医用几丁糖纳米微球的制备方法为:
S1油相体系的制备:量取定量液体石蜡缓慢加入圆底烧瓶中,加入定量乳化剂,搅拌圆底烧瓶中的液体直至混匀,形成油相体系,得到油相,备用;
S2水相体系的制备:量取定量壳聚糖溶于定量1%醋酸溶液中,后取定量乙醇加入,使用超声搅拌器搅拌1h,形成水相体系,得到水相,备用;
S3乳浊液的制备:使用1mL移液器吸取水相,缓慢多次的滴加到油相中,离心搅拌20~30min,离心条件为500~1000rpm,得到乳状油包水乳浊液;
S4搅拌:在乳浊液中缓慢加入定量人参皂苷Rg3、多巴胺和BFGF,用超声波搅拌器充分搅拌1~1.5h,后加入交联剂,搅拌混匀;
S5离心分离:将经步骤S4处理后的乳浊液倒入离心管中,经离心机进行离心处理25min;
S6一次洗涤:向离心管中加入15mL石油醚洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置6~8min,吸除分层后的上清液;
S7二次洗涤:向经步骤S6处理后的离心管中加入15mL丙酮洗涤3次,置于离心机中室温离心20min,离心条件为1200rpm,静置6~8min;
S8干燥保存:吸除经步骤S7处理分层后的上清液,冷冻干燥后得到医用几丁糖纳米微球,收集并置于干燥环境下保存。
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