CN106512077B - 一种利用明胶制备的温敏型止血凝胶用促凝助剂 - Google Patents
一种利用明胶制备的温敏型止血凝胶用促凝助剂 Download PDFInfo
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Abstract
本发明公开了一种利用明胶制备的温敏型止血凝胶用促凝助剂,涉及止血凝胶技术领域,由如下重量份数的原料制成:明胶20‑25份、聚乙二醇4000 4‑8份、羟丙基甲基纤维素3‑6份、半胱氨酸2‑4份、聚丙烯酸2‑4份、鲸蜡醇1‑2份、维生素C 1‑2份、小苏打0.5‑1份、柠檬酸钙0.5‑1份、水杨酸钠0.5‑1份、熊果苷0.3‑0.5份、香草醇丁醚0.3‑0.5份、乙醇10‑15份、水40‑50份。本发明促凝助剂主要应用于协同皮胶原止血成分制备温敏型止血凝胶,以提高止血效果和缩短止血时间。
Description
技术领域:
本发明涉及止血凝胶技术领域,具体涉及一种利用明胶制备的温敏型止血凝胶用促凝助剂。
背景技术:
在外科和创伤手术中经常会伴随着创面的大量出血,从而使患者面临极大的生命危险,因此制备快速有效的止血材料一直作为医用领域的研究热点。传统的止血材料主要是四头带、止血带和绷带等,这类材料不易携带和消毒保存,且止血几乎靠机械作用,止血效果不好。近年来,人们研制出生物可吸收止血材料,其中动物皮胶原基材料作为一种生物性能良好的医用材料,与人体具有良好的组织相容性,可生物降解且无毒副作用,同时能够促进细胞的粘附、增殖和创口的复合;并且通过其特有的微孔结构和良好的粘附性,促进生物因子的生长扩散,诱导并促进成纤维细胞的生长,从而促进伤口的愈合。
目前,普遍的动物皮胶原提取制备方法为酸酶结合提取法,主要包括原料的预处理、脱脂、酶解消化、盐析、离心和纯化等步骤,但存在所得皮胶原纯度和产率低、成本高等问题,并且会因提取过程中处理不当而降低皮胶原的止血效果。针对这一问题,本公司通过添加利用明胶制备的促凝助剂的方法,来提高以皮胶原为主要止血成分的温敏型止血凝胶的止血效果,缩短止血时间。
发明内容:
本发明所要解决的技术问题在于提供一种旨在协同皮胶原止血材料提高止血效果以缩短止血时间的利用明胶制备的温敏型止血凝胶用促凝助剂。
本发明所要解决的技术问题采用以下的技术方案来实现:
一种利用明胶制备的温敏型止血凝胶用促凝助剂,由如下重量份数的原料制成:
明胶20-25份、聚乙二醇40004-8份、羟丙基甲基纤维素3-6份、半胱氨酸2-4份、聚丙烯酸2-4份、鲸蜡醇1-2份、维生素C 1-2份、小苏打0.5-1份、柠檬酸钙0.5-1份、水杨酸钠0.5-1份、熊果苷0.3-0.5份、香草醇丁醚0.3-0.5份、乙醇10-15份、水40-50份。
其制备方法包括如下步骤:
(1)将明胶加入乙醇与水的混合溶剂中,搅拌使其分散均匀,静置30min后加入聚乙二醇4000和水杨酸钠,充分混合,再利用等离子表面处理机对所得混合物处理10s,然后加入半胱氨酸和维生素C,混合均匀后再次利用等离子表面处理机处理10s,即得浆料I;
(2)向浆料I中加入羟丙基甲基纤维素、聚丙烯酸和鲸蜡醇,并加热至60-65℃保温混合10min,再迅速转入0-5℃环境中静置3h,然后加热至回流状态保温混合5min,所得浆料自然冷却至室温,即得浆料II;
(3)向浆料II中加入小苏打和柠檬酸钙,充分混合后利用微波反应器处理3min,然后在冰水浴下以10-15℃/min的速度冷却降温,待温度降至5-10℃后加入熊果苷和香草醇丁醚,混合均匀,最后将所得混合浆料送入冷冻干燥机中,充分干燥后研磨成粉末。
所述等离子表面处理机的工作频率40Hz、输出功率600W。
所述微波反应器的工作频率2450MHz、输出功率700W。
所述聚丙烯酸使用前经过化学改性,其改性方法为:将聚丙烯酸和酪氨酸加入两倍重量份乙醇中,分散均匀后加热至回流状态保温搅拌10min,再加入白藜芦醇和乙二胺四乙酸二钠,继续于回流状态下保温搅拌30min,所得混合物自然冷却至35-40℃后立即转入0-5℃环境中静置8h,然后送入喷雾干燥机中,干燥后所得固体经研磨制成粉末。
所述聚丙烯酸、酪氨酸、白藜芦醇和乙二胺四乙酸二钠的用量比为10:1:3:0.5。
本发明的有益效果是:本发明以明胶为主要原料,经过交联与聚合反应,并辅以多种助剂制得促凝助剂,该促凝助剂主要应用于协同皮胶原止血成分制备温敏型止血凝胶,以提高止血效果和缩短止血时间,经研究发现添加有该促凝助剂的止血凝胶的止血时间比原来缩短20%左右,并且具有优异的生物相容性与生物降解性,对人体的使用安全性高。
具体实施方式:
为了使本发明实现的技术手段、创作特征、达成目的与功效易于明白了解,下面结合具体实施例,进一步阐述本发明。
实施例1
(1)将20份明胶加入10份乙醇与40份水的混合溶剂中,搅拌使其分散均匀,静置30min后加入4份聚乙二醇4000和1份水杨酸钠,充分混合,再利用等离子表面处理机对所得混合物处理10s,然后加入2份半胱氨酸和1份维生素C,混合均匀后再次利用等离子表面处理机处理10s,即得浆料I;
(2)向浆料I中加入3份羟丙基甲基纤维素、2份聚丙烯酸和1份鲸蜡醇,并加热至60-65℃保温混合10min,再迅速转入0-5℃环境中静置3h,然后加热至回流状态保温混合5min,所得浆料自然冷却至室温,即得浆料II;
(3)向浆料II中加入1份小苏打和0.5份柠檬酸钙,充分混合后利用微波反应器处理3min,然后在冰水浴下以10-15℃/min的速度冷却降温,待温度降至5-10℃后加入0.5份熊果苷和0.3份香草醇丁醚,混合均匀,最后将所得混合浆料送入冷冻干燥机中,充分干燥后研磨成粉末。
其中,等离子表面处理机的工作频率40Hz、输出功率600W;微波反应器的工作频率2450MHz、输出功率700W。
聚丙烯酸的化学改性:将10份聚丙烯酸和1份酪氨酸加入两倍重量份乙醇中,分散均匀后加热至回流状态保温搅拌10min,再加入3份白藜芦醇和0.5份乙二胺四乙酸二钠,继续于回流状态下保温搅拌30min,所得混合物自然冷却至35-40℃后立即转入0-5℃环境中静置8h,然后送入喷雾干燥机中,干燥后所得固体经研磨制成粉末。
实施例2
(1)将25份明胶加入15份乙醇与45份水的混合溶剂中,搅拌使其分散均匀,静置30min后加入6份聚乙二醇4000和0.5份水杨酸钠,充分混合,再利用等离子表面处理机对所得混合物处理10s,然后加入3份半胱氨酸和1份维生素C,混合均匀后再次利用等离子表面处理机处理10s,即得浆料I;
(2)向浆料I中加入5份羟丙基甲基纤维素、3份聚丙烯酸和1份鲸蜡醇,并加热至60-65℃保温混合10min,再迅速转入0-5℃环境中静置3h,然后加热至回流状态保温混合5min,所得浆料自然冷却至室温,即得浆料II;
(3)向浆料II中加入0.5份小苏打和0.5份柠檬酸钙,充分混合后利用微波反应器处理3min,然后在冰水浴下以10-15℃/min的速度冷却降温,待温度降至5-10℃后加入0.5份熊果苷和0.3份香草醇丁醚,混合均匀,最后将所得混合浆料送入冷冻干燥机中,充分干燥后研磨成粉末。
其中,等离子表面处理机的工作频率40Hz、输出功率600W;微波反应器的工作频率2450MHz、输出功率700W。
聚丙烯酸的化学改性:将10份聚丙烯酸和1份酪氨酸加入两倍重量份乙醇中,分散均匀后加热至回流状态保温搅拌10min,再加入3份白藜芦醇和0.5份乙二胺四乙酸二钠,继续于回流状态下保温搅拌30min,所得混合物自然冷却至35-40℃后立即转入0-5℃环境中静置8h,然后送入喷雾干燥机中,干燥后所得固体经研磨制成粉末。
以上显示和描述了本发明的基本原理和主要特征和本发明的优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明精神和范围的前提下,本发明还会有各种变化和改进,这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。
Claims (4)
1.一种利用明胶制备的温敏型止血凝胶用促凝助剂,其特征在于,由如下重量份数的原料制成:
明胶20-25份、聚乙二醇4000 4-8份、羟丙基甲基纤维素3-6份、半胱氨酸2-4份、聚丙烯酸2-4份、鲸蜡醇1-2份、维生素C 1-2份、小苏打0.5-1份、柠檬酸钙0.5-1份、水杨酸钠0.5-1份、熊果苷0.3-0.5份、香草醇丁醚0.3-0.5份、乙醇10-15份、水40-50份;
其制备方法包括如下步骤:
(1)将明胶加入乙醇与水的混合溶剂中,搅拌使其分散均匀,静置30min后加入聚乙二醇4000和水杨酸钠,充分混合,再利用等离子表面处理机对所得混合物处理10s,然后加入半胱氨酸和维生素C,混合均匀后再次利用等离子表面处理机处理10s,即得浆料I;
(2)向浆料I中加入羟丙基甲基纤维素、聚丙烯酸和鲸蜡醇,并加热至60-65℃保温混合10min,再迅速转入0-5℃环境中静置3h,然后加热至回流状态保温混合5min,所得浆料自然冷却至室温,即得浆料II;
(3)向浆料II中加入小苏打和柠檬酸钙,充分混合后利用微波反应器处理3min,然后在冰水浴下以10-15℃/min的速度冷却降温,待温度降至5-10℃后加入熊果苷和香草醇丁醚,混合均匀,最后将所得混合浆料送入冷冻干燥机中,充分干燥后研磨成粉末;
所述聚丙烯酸使用前经过化学改性,其改性方法为:将聚丙烯酸和酪氨酸加入两倍重量份乙醇中,分散均匀后加热至回流状态保温搅拌10min,再加入白藜芦醇和乙二胺四乙酸二钠,继续于回流状态下保温搅拌30min,所得混合物自然冷却至35-40℃后立即转入0-5℃环境中静置8h,然后送入喷雾干燥机中,干燥后所得固体经研磨制成粉末。
2.根据权利要求1所述的利用明胶制备的温敏型止血凝胶用促凝助剂,其特征在于:所述等离子表面处理机的工作频率40Hz、输出功率600W。
3.根据权利要求1所述的利用明胶制备的温敏型止血凝胶用促凝助剂,其特征在于:所述微波反应器的工作频率2450MHz、输出功率700W。
4.根据权利要求1所述的利用明胶制备的温敏型止血凝胶用促凝助剂,其特征在于:所述聚丙烯酸、酪氨酸、白藜芦醇和乙二胺四乙酸二钠的用量比为10:1:3:0.5。
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