CN117327171B - 一种改性重组人源化胶原蛋白及其在***敷料中的应用 - Google Patents
一种改性重组人源化胶原蛋白及其在***敷料中的应用 Download PDFInfo
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- CN117327171B CN117327171B CN202311631888.4A CN202311631888A CN117327171B CN 117327171 B CN117327171 B CN 117327171B CN 202311631888 A CN202311631888 A CN 202311631888A CN 117327171 B CN117327171 B CN 117327171B
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Abstract
本发明公开了一种改性重组人源化胶原蛋白及其在***敷料中的应用,改性重组人源化胶原蛋白是由重组人源化胶原蛋白和没食子酸酮酯通过席夫碱反应而得,所述没食子酸酮酯包括三羟基苯基、酮基、烷基,大大提高了重组人源化胶原蛋白在粘膜上的粘附性、以及消炎抗菌性。
Description
技术领域
本发明属于合成生物医学材料技术领域,具体涉及一种改性重组人源化胶原蛋白及其在***敷料中的应用。
背景技术
人源胶原蛋白是一种主要存在于人体***中的蛋白质,具有以下好处:a. 维持组织结构:胶原蛋白是构成皮肤、血管、骨骼和关节等组织的重要成分,可以提供组织的力学强度和结构支持。b. 促进伤口愈合:胶原蛋白具有促进细胞迁移和增殖的作用,可以加速创伤或手术后的伤口愈合过程。c. 保湿和滋润:胶原蛋白具有良好的保水能力,能够在皮肤或黏膜表面形成保护性的水分屏障,有助于保持皮肤或黏膜的湿润。d. 改善组织弹性:胶原蛋白在皮肤和黏膜中起到支撑和弹性的作用,能够改善组织的弹性和紧致度。目前,含有胶原蛋白的***凝胶已经引起了广泛的关注和研究,主要应用于以下方面:a. ***萎缩治疗:胶原蛋白的补充可以改善***黏膜的弹性和紧致性,对于因为衰老、分娩或激素变化等原因导致的***萎缩症状的改善和治疗具有一定效果。b. 干燥和炎症治疗:胶原蛋白具有良好的保湿和滋润性,并具有一定的抗炎作用,可以在***干燥、炎症、创伤等情况下,为***黏膜提供保护和修复功能。c. 人工排尿通道修复:在尿道瘘和尿道周围组织缺损的修复中,胶原蛋白被用作支架材料,可以改善尿道结构和功能恢复。虽然含有胶原蛋白的***凝胶具有一定的优势,但缺乏长效持续性,目前的***凝胶技术往往需要频繁的使用和补充,因为胶原蛋白在皮肤黏膜的上的粘合度有限,且降解和吸收速度较快,无法实现长效持续的治疗效果。
发明内容
本发明提供一种改性重组人源化胶原蛋白,该凝胶含有改性重组人源化胶原蛋白,所述改性重组人源化胶原蛋白由没食子酸酯与胶原蛋白反应而成。
所述改性重组人源化胶原蛋白制备方法包括以下步骤:
(1)制备没食子酸酮酯
3,4,5-三乙氧基苯甲酸与氯化亚砜在DMF中加热至50~60℃进行反应,粗产物减压旋蒸得到3,4,5-三乙氧基苯甲酰氯;3,4,5-三乙氧基苯甲酰氯溶于DMF中,加入缚酸剂,然后与醇酮化合物在40~60℃下反应,粗产物过滤后,取滤液旋蒸后得到含有三乙酰没食子酸酮酯的粗产物;将含有三乙酰没食子酸酮酯的粗产物在碳酸氢钠的无水乙醇饱和溶液中搅拌至溶液pH不再发生变化,溶液纯化后即得到没食子酸酮酯。
所述缚酸剂选自三乙胺或吡啶;所述纯化是指溶液挥干溶剂后,加入甲苯重新溶解,然后重结晶得到产物。
所述醇酮化合物选自1-羟基-3-癸酮、1-羟基-6-十四酮、1-羟基-4-十二酮、1-羟基-3-壬酮、7-羟基-2,4-庚二酮、6-羟基-2,4-己二酮中的一组或组合。
(2)制备改性重组人源化胶原蛋白
配制备重组人源化胶原蛋白溶液和没食子酸酮酯溶液,然后加碱调节溶液pH为7~10,于30~50℃下反应2~4h,得到改性重组人源化胶原蛋白。
所述溶液是指将重组人源化胶原蛋白或没食子酸酮酯溶于水、乙醇、丙酮、DMSO中的一种或组合;所述碱为NaOH或KOH或Na2CO3。
所述重组人源化胶原蛋白包括不限于I型、II型、III型蛋白,重组人源化III型胶原蛋白作为优选。
所述重组人源化胶原蛋白和没食子酸酮酯的投料质量比例为(10~30):1,其中重组人源化胶原蛋白以干基计算。
本发明提供一种改性重组人源化胶原蛋白,所述改性胶原蛋白医用***敷料包括改性重组人源化胶原蛋白、凝胶基质、增稠剂、防腐剂、保湿剂、pH调节剂。
所述凝胶基质选自卡波姆、黄原胶、海藻酸盐、壳聚糖、透明质酸、泊洛沙姆中的一种或多种。
所述增稠剂剂选自甲基纤维素、羧甲基纤维素钠、乙基纤维素、羟乙基纤维素、氰乙基纤维素、羟丙基纤维素和羟丙基甲基纤维素中的一种或多种。
所述防腐剂选自为尼泊金酯、苯甲酸钠、苯氧乙醇中的一种或多种。
所述保湿剂选自氨基酸、透明质酸、甘油、丙二醇中的一种或多种。
所述pH调节剂为乳酸。
所述改性胶原蛋白医用***敷料的pH值为3.5~4.2。
进一步的本发明提供一种改性重组人源化胶原蛋白,按质量百分比计算,包括以下组分:改性重组人源化胶原蛋白1~3%、凝胶基质5~15%、增稠剂1~3%、防腐剂0.01~0.2%、保湿剂0~10%、pH调节剂0~1%,余量为水。
有益效果
本发明提供的改性重组人源化胶原蛋白在皮肤黏膜具有良好的粘附性,且改性后胶原蛋白的消炎抑菌性能大大提高;试验证明,添加改性重组人源化胶原蛋白的***凝胶对小鼠真菌性***炎具有良好的治疗效果。
附图说明
图1为试验例4关于改性重组人源化胶原蛋白在细胞表面的粘附性结果。
图2为试验例4关于细胞在改性重组人源化胶原蛋白处理后的玻片上的细胞迁移实验。
具体实施方式
下面结合具体实施例对本发明做进一步详细说明,但实施例并不对本发明做任何形式的限定。除非特别说明,本发明采用的试剂、方法和设备为本技术领域常规试剂、方法和设备。
实施例1
制备1-(没食子酰氧基)癸烷-3-酮。
按投料比称取3,4,5-三乙氧基苯甲酸溶于DMF中,并加入氯化亚砜搅拌均匀后,升温至55℃搅拌反应5h,反应产物旋蒸除溶和过量的氯化亚砜,得到3,4,5-三乙氧基苯甲酰氯;所述3,4,5-三乙氧基苯甲酸与氯化亚砜的投料摩尔比为1:3;
称取3,4,5-三乙氧基苯甲酰氯重新溶于DMF中,加入三乙胺和1-羟基-3-癸酮,搅拌均匀后升温至60℃,随着反应的进行,三乙胺盐酸盐析出,反应至沉淀不再明显增加(大约10h),停止加热,反应液过滤后,取滤液减压蒸馏,得到粗产物;将粗产物在碳酸氢钠的无水乙醇饱和溶液中常温下搅拌至溶液pH不再发生变化(大约3h),旋蒸除溶后,以甲苯重结晶,干燥后即得到1-(没食子酰氧基)癸烷-3-酮。
1-(没食子酰氧基)癸烷-3-酮结构式如下:
1H-NMR(CDCl3ppm):0.75 ( t , CH3) , 1.22~1.25 ( m , CH2CH2CH2CH2) ,1.48 ( m , CH2) , 1.95 ( t , COCH2) , 2.84 ( t , COCH2) , 4.22 ( t , COOCH2) ,7.15 ( s , ArH ) , 8.26 ( s, ArOH ) , 8.89 ( s, ArOH )。
实施例2
制备1-(没食子酰氧基)壬烷-3-酮,反应步骤与实施例1相同。
1H-NMR(CDCl3ppm):0.74 ( t , CH3) , 1.24~1.26 ( m , CH2CH2CH2) , 1.52( m , CH2) , 1.97 ( t , COCH2) , 3.12 ( t , COCH2) , 4.26 ( t , COOCH2) , 7.13( s , ArH ) , 8.24 ( s, ArOH ) , 8.96 ( s, ArOH )。
实施例3
制备1-(没食子酰氧基)十二烷-4-酮,反应步骤与实施例1相同。
1H-NMR(CDCl3ppm):0.78 ( t , CH3) , 1.25~1.29 ( m , CH2CH2CH2CH2CH2) ,1.52 ( m , CH2) , 2.08 ( m , CH2) , 2.45( t , CH2COCH2) , 4.25 ( t , COOCH2) ,7.02 ( s , ArH ) , 8.55 ( s, ArOH ) , 9.11 ( s, ArOH )。
实施例4
制备1-(没食子酰氧基)十四烷6-酮,反应步骤与实施例1相同。
1H-NMR(CDCl3ppm):0.85 ( t , CH3) , 1.26~1.33 ( m , CH2CH2CH2CH2CH2CH2), 1.24 ( m , CH2) , 1.52 ( m , CH2 , 4) , 1.75 ( m , CH2 ) , 2.35 ( t ,CH2COCH2) , 4.27 ( t , COOCH2) , 7.02 ( s , ArH ) , 8.55 ( s, ArOH ) , 9.11 (s, ArOH )。
实施例5
制备6-(没食子酰氧基)己烷-2,4-二酮,反应步骤与实施例1相同。
1H-NMR(CDCl3ppm):2.17 ( s, COCH3) , 3.28 ( t , COCH2) , 3.55 ( s ,COCH2CO ) , 4.42 ( t , COOCH2) , 7.14 ( s , ArH ) , 8.74 ( s, ArOH ) , 8.98 (s, ArOH )。
实施例6
制备7-(没食子酰氧基)庚烷-2,4-二酮,反应步骤与实施例1相同。
1H-NMR(CDCl3ppm):2.05 ( m , CH2 ) , 2.20 ( s, COCH3) , 2.35 ( t ,COCH2) , 3.63 ( s , COCH2CO ) , 4.42 ( t , COOCH2) , 7.13 ( s , ArH ) , 8.68( s, ArOH ) , 8.87 ( s, ArOH )。
实施例7
制备改性重组人源化胶原蛋白1。
分别配制一下溶液:
溶液①:15wt%重组人源化III型胶原蛋白水溶液;
溶液②:10wt% 1-(没食子酰氧基)壬烷-3-酮的乙醇溶液;
①和②溶液的投加体积比例为134:10。
将溶液①和溶液②混合后,用1M的Na2CO3的水溶液调节pH值至7.8,升温至50℃反应3h后,继续加入溶液③,保温反应2h,产物浓缩后在离子水中透析3d(6h换水一次),干燥后即得到改性重组人源化胶原蛋白1。
实施例8
制备改性重组人源化胶原蛋白2。
分别配制一下溶液:
溶液①:15wt%重组人源化III型胶原蛋白水溶液;
溶液②:10wt% 1-(没食子酰氧基)壬烷-3-酮的乙醇溶液;
溶液③:5wt% 7-(没食子酰氧基)庚烷-2,4-二酮的乙醇溶液。
①、②、③溶液的投加体积比例为134:7:6。
将溶液①和溶液②混合后,用1M的NaOH的水溶液调节pH值至8.2,升温至50℃反应2h后,继续加入溶液③,保温反应2h,产物浓缩后在离子水中透析3d(6h换水一次),干燥后即得到改性重组人源化胶原蛋白2。
实施例9
制备改性重组人源化胶原蛋白3。
分别配制一下溶液:
溶液①:15wt%重组人源化III型胶原蛋白乙醇溶液;
溶液②:10wt% 1-(没食子酰氧基)壬烷-3-酮的乙醇溶液;
溶液③:5wt% 7-(没食子酰氧基)庚烷-2,4-二酮的乙醇溶液。
①、②、③溶液的投加体积比例为134:5:10。
将溶液①和溶液②混合后,用1M的NaOH的水溶液调节pH值至8.1,升温至50℃反应2h后,继续加入溶液③,保温反应2h,产物浓缩后在离子水中透析3d(6h换水一次),干燥后即得到改性重组人源化胶原蛋白3。
实施例10
制备改性重组人源化胶原蛋白4。
分别配制一下溶液:
溶液①:15wt%重组人源化III型胶原蛋白DMSO溶液;
溶液②:10wt% 1-(没食子酰氧基)1-(没食子酰氧基)十二烷-4-酮的DMSO溶液;
溶液③:5wt% 6-(没食子酰氧基)己烷-2,4-二酮的DMSO溶液。
①、②、③溶液的投加体积比例为134:7:6。
将溶液①和溶液②混合后,用1M的NaOH的水溶液调节pH值至8.1,升温至50℃反应2h后,继续加入溶液③,保温反应2h,产物浓缩后在离子水中透析3d(6h换水一次),干燥后即得到改性重组人源化胶原蛋白4。
对比例1
制备没食子酸改性重组人源化胶原蛋白,方法如下:
配制2wt%的没食子酸水溶液,然后加入碳二亚胺,常温条件下反应20min使羧基活化,然后加入15wt%的重组人源化III型胶原蛋白水溶液,以醋酸溶液调节pH值至4.5,常温下搅拌反应5h,反应液浓缩后在离子水中透析3d(6h换水一次),干燥后即得到食子酸改性重组人源化胶原蛋白。所述没食子酸、碳二亚胺、重组人源化III型胶原蛋白的投料质量比为0.8:1:20。
对比例2
制备邻苯二酚改性重组人源化胶原蛋白,方法如下:
采用3,4-二乙氧基苯甲酸代替实施例2的3,4,5-三乙氧基苯甲酸,采用相同的方法制备得到1-(原儿茶酰氧基)壬烷-3-酮,具有如下结构:
1H-NMR(CDCl3ppm):0.73 ( t , CH3) , 1.24~1.26 ( m , CH2CH2CH2) , 1.52( m , CH2) , 2.12 ( t , COCH2) , 3.16 ( t , COCH2) , 4.36 ( t , COOCH2) , 7.15~7.23 ( m , ArH ) , 9.14 ( s, ArOH ) , 9.17 ( s, ArOH )。
采用实施例7相同的方法制备1-(原儿茶酰氧基)壬烷-3-酮改性重组人源化III型胶原蛋白。
试验例1 细胞毒性
将改性重组人源化胶原蛋白配制成不同浓度的培养基溶液,将VK2/E6E7细胞(人源***上皮细胞,购于ATCC)在96孔培养板上以1.0×105细胞/mL的密度用DMEM F12培养基进行培养,培养过夜后,以含有改性重组人源化胶原蛋白的培养基替换原来培养基,继续将在37℃、CO2浓度为5 %的培养箱中培养过夜。细胞培养24h后,向孔中加入5.0 mg/mL浓度的MTT(PBS溶液),再在37℃下培养4 h。随后去除培养基,加入150μLDMSO,然后剧烈震动以溶解形成的紫色甲瓒晶体。用Wellscan Mk 3酶标仪在570 nm的波长下测量吸光度,并计算细胞存活率,结果列于表2。
由实验结果可知,改性胶原蛋白的浓度在30mg/mL以内使用时具有安全性的,改性后的胶原蛋白由于带有醛基,以及反应过程中不可避免的杂质残留,使得改性胶原蛋白的毒性相较于纯的胶原蛋白与对比例1的没食子酸改性胶原蛋白更高,但在安全的使用浓度范围内是毒性较少的。
试验例2 抑菌活性
以大肠杆菌、白色念珠菌、加德纳菌作为测试菌种,使用抑菌圈法测定凝胶的抑菌性。具体如下:菌液为用PBS缓冲溶液分别稀释到1×107CFU/mL,均匀涂布在无菌的LB固体琼脂培养基上,向每个圆孔中加入30μL改性重组人源化胶原蛋白溶液(浓度为7.5mg/mL)。将需氧菌于电热恒温培养箱内37℃培养24h,厌氧菌先放入厌氧罐后置于同一培养箱内37℃培养48h,待培养好后,用Scan-1200微生物技术仪拍照并测量抑菌圈直径。
大肠杆菌(25922)、白色念珠菌(10231)和加德纳菌(14018)购于ATCC。
各改性重组人源化胶原蛋白的抑菌圈直径列于表3。
抑菌活性实验结果表明,实施例与对比例的抑菌活性要高于纯胶原蛋白,因为酚类物质具有天然的抗菌药性,胶原蛋白中酚基越多,改性胶原蛋白的抑菌活性越高。对比例1为没食子酸改性胶原蛋白,由于相同质量投料比的情况下,酚基的含量更高,因此获得更好的抗菌性;对比例2的改性剂为1-(原儿茶酰氧基)壬烷-3-酮,相比于实施例,酚羟基含量较低,因此抑菌活性相对较低。
试验例3 消炎效果
以10ng/mL的IL-1刺激VK2/E6E7细胞模型,利用ELISA测试IL-6和IL-8的含量,评价改性重组人源化胶原蛋白的消炎效果,具体如下:
将细胞接种至6孔板中,采用DMEM F12培养基进行培养,至细胞铺板率达到40~60%时,加入10ng/mL的IL-1诱导工作液进行诱导,同时试验组加入改性重组人源化胶原蛋白溶液(终浓度为7.5mg/mL),阳性对照组加入***(终浓度为0.8ng/mL),然后置于37℃,5%CO2的培养箱中孵育24h,然后收集培养液于离心管中,采用ELISA试剂盒进行检测,IL-6和IL-8的平均浓度列于表4。
由试验例3结果可知,实施例相比于重组人源化III型胶原蛋白具有更高的抗炎性,其抗炎效果虽然不及***,但***是一种糖皮质激素,长期使用会产生依赖性且有副作用,而本发明提供改性胶原蛋白作为抗炎活性物质安全性更高。另外,与对比例1和2相比,实施例的抗炎效果更优。
试验例4 粘膜粘附性
将采用两种方式评价改性重组人源化胶原蛋白的粘膜粘附性,分别为紫外光谱法和细胞迁移实验。
紫外光谱法:将VK2/E6E7细胞移植至6孔板中,采用DMEM F12培养基进行培养,至细胞铺板率达到80%时,用含有改性重组人源化胶原蛋白的培养基(浓度为30mg/mL)替换原来的培养基,继续培养若干时间后取样进行紫外光谱测试,观察210~220nm吸收峰强度(没食子酸酯/原儿茶酸酯的苯环吸收),通过吸光度大小判断改性重组人源化胶原蛋白在细胞表面的粘附性,吸收峰强度的剩余比例结果列于附图1。
细胞迁移实验:以改性重组人源化胶原蛋白对盖玻片进行处理,然后将盖玻片放置于上述细胞铺板率达到80%的六孔板中央,继续培养24h后观察盖玻片表面的细胞迁移情况。结果参阅附图2。
改性重组人源化胶原蛋白对盖玻片进行处理是指:把盖玻片置于在4wt%的3-氨基丙基三甲氧基硅烷溶液中浸泡15min,然后用去离子水清洗干净,再用0.5wt%的戊二醛溶液处理30min,最后将盖玻片用去离子水彻底清洗,干燥后加入至含有30mg/mL改性重组人源化胶原蛋白和6mM冰醋酸的混合溶液中,常温下孵化12h后用去离子水冲洗表面,得到改性重组人源化胶原蛋白处理的盖玻片。
从附图1和2的结果显示,实施例与对比例相比,没食子酸酮酯改性胶原蛋白对细胞的粘附性更强,这是由于酚羟基与醛基是细胞粘附性的来源,酚羟基能够与细胞表面形成氢键,从而产生较高的粘附性;而醛基能够与细胞表面的氨基反应形成可逆键从而粘附在细胞表面。另外,对比实施例7~10,没食子酸酮酯的烷基链越长,对细胞粘附性越高,这是由于疏水长脂肪链有利于提高胶原蛋白在水下的长期稳定性。由于没食子酸具有很高的水溶性,改性后会使得胶原蛋白的水溶性更高,与细胞粘合时较难排除细胞表面的水膜,导致粘附性降低,但加入疏水分子链后,利用疏水链段排除界面水膜,能够大大提高蛋白的粘附性。
综上所述,本发明的改性胶原蛋白具有优异的综合性能,在安全使用浓度范围内,具有良好的抑菌活性、抗炎性及细胞粘附性,能够在皮肤黏膜上持久的发挥药性,延长药物使用寿命,从而提高药效。
实施例11
制备一种改性重组人源化胶原蛋白,配方如下:
改性重组人源化胶原蛋白4(实施例10):1%;透明质酸:0.5%;泊洛沙姆407:10%;泊洛沙姆188:0 .5%;羧甲基纤维素钠:1%;苯氧乙醇:0.1%;甘油:3%,余量为水。
先将凝胶基质、保湿剂、增稠剂溶解到纯水中,搅拌均匀,然后加入用0.22μm的膜过滤过的改性重组人源化胶原蛋白,继续搅拌,得到均匀体系,再加入防腐剂,然后用纯水将余量补足,搅拌均匀,然后加入乳酸调节pH值至3.8,即得成品。
实施例12
制备一种改性重组人源化胶原蛋白,配方如下:
改性重组人源化胶原蛋白4(实施例10):2%;透明质酸:0.5%;泊洛沙姆407:10%;泊洛沙姆188:0 .5%;羧甲基纤维素钠:1%;苯氧乙醇:0.1%;甘油:3%,余量为水。
先将凝胶基质、保湿剂、增稠剂溶解到纯水中,搅拌均匀,然后加入用0.22μm的膜过滤过的改性重组人源化胶原蛋白,继续搅拌,得到均匀体系,再加入防腐剂,然后用纯水将余量补足,搅拌均匀,然后加入乳酸调节pH值至3.8,即得成品。
实施例13
制备一种改性重组人源化胶原蛋白,配方如下:
改性重组人源化胶原蛋白4(实施例10):3%;透明质酸:0.5%;泊洛沙姆407:10%;泊洛沙姆188:0 .5%;羧甲基纤维素钠:1%;苯氧乙醇:0.1%;甘油:3%,余量为水。
先将凝胶基质、保湿剂、增稠剂溶解到纯水中,搅拌均匀,然后加入用0.22μm的膜过滤过的改性重组人源化胶原蛋白,继续搅拌,得到均匀体系,再加入防腐剂,然后用纯水将余量补足,搅拌均匀,然后加入乳酸调节pH值至3.8,即得成品。
实施例14
制备一种改性重组人源化胶原蛋白,配方如下:
改性重组人源化胶原蛋白5:3%;卡波姆U20:10%;透明质酸:1%;羧甲基纤维素钠:2%;苯氧乙醇:0.1%;丙二醇:2%,余量为水。
所述改性重组人源化胶原蛋白5系由重组人源化II型胶原蛋白、1-(没食子酰氧基)癸烷-3-酮、7-(没食子酰氧基)庚烷-2,5-二酮制备而成,三者的质量比例为30:0.7:0.3,制备方法同实施例8。
先将凝胶基质、保湿剂、增稠剂溶解到纯水中,搅拌均匀,然后加入用0.22μm的膜过滤过的改性重组人源化胶原蛋白,继续搅拌,得到均匀体系,再加入防腐剂,然后用纯水将余量补足,搅拌均匀,然后加入乳酸调节pH值至4,即得成品。
实施例15
制备一种改性重组人源化胶原蛋白,配方如下:
改性重组人源化胶原蛋白6:1%;泊洛沙姆407:12%;泊洛沙姆188:1%;黄原胶:0.2%;透明质酸:1%;羧甲基纤维素钠:1%;尼泊金乙酯:0.1%;甘油:2%,余量为水。
所述改性重组人源化胶原蛋白6系由重组人源化I型胶原蛋白、1-(没食子酰氧基)十二烷-4-酮、7-(没食子酰氧基)庚烷-2,5-二酮制备而成,三者的质量比例为10:0.7:0.3,制备方法同实施例8。
先将凝胶基质、保湿剂、增稠剂溶解到纯水中,搅拌均匀,然后加入用0.22μm的膜过滤过的改性重组人源化胶原蛋白,继续搅拌,得到均匀体系,再加入防腐剂,然后用纯水将余量补足,搅拌均匀,然后加入乳酸调节pH值至3.6,即得成品。
对比例3
制备一种改性重组人源化胶原蛋白,配方如下:
重组人源化III型胶原蛋白:2%;透明质酸:0.5%;泊洛沙姆407:10%;泊洛沙姆188:0 .5%;羧甲基纤维素钠:1%;苯氧乙醇:0.1%;甘油:3%,余量为水。
先将凝胶基质、保湿剂、增稠剂溶解到纯水中,搅拌均匀,然后加入用0.22μm的膜过滤过的重组人源化胶原蛋白,继续搅拌,得到均匀体系,再加入防腐剂,然后用纯水将余量补足,搅拌均匀,然后加入乳酸调节pH值至3.8,即得成品。
试验例5 大鼠***炎模型试验
将大鼠固定后,镊起其***口,用灌胃针头注入庆大霉素和青霉素的混合液,连续脱污染5天后,取***分泌物培养病原体,检查为阴性。皮下注射***建立假动情期,皮下注射氢化可的松诱导免疫抑制。处于假动情期的大鼠,用针头在距***口1cm处对黏膜作环形创伤,注入白色念珠菌(3×108CFU/ml),注入剂量为0.6ml/kg,用凝胶海绵堵住***外口。隔日再注射1次。接种后的第7天,取***分泌物做镜检及真菌培养,镜检及菌株鉴定均为阳性者即为感染成功。
取感染成功的大鼠随机分为6组:实施例11-15和对比例1的抑***凝胶,每组动物5只。另取5只感染大鼠不予治疗,设为空白组。于接种第7天后,连续给药5天。停药后第1、3天取大鼠***分泌物进行检查,确定是否转阴。实验结果见表5。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (10)
1.一种改性重组人源化胶原蛋白的制备方法,其特征在于,包括如下步骤:
(1)制备没食子酸酮酯
3,4,5-三乙氧基苯甲酸与氯化亚砜在DMF中加热至50~60℃进行反应,粗产物减压旋蒸得到3,4,5-三乙氧基苯甲酰氯;3,4,5-三乙氧基苯甲酰氯溶于DMF中,加入缚酸剂,然后与醇酮化合物在40~60℃下反应,粗产物过滤后,取滤液旋蒸后得到含有三乙酰没食子酸酮酯的粗产物;将含有三乙酰没食子酸酮酯的粗产物在碳酸氢钠的无水乙醇饱和溶液中搅拌至溶液pH不再发生变化,溶液纯化后即得到没食子酸酮酯;
(2)制备改性重组人源化胶原蛋白
配制重组人源化胶原蛋白溶液和没食子酸酮酯溶液,然后加碱调节溶液pH为7~10,于30~50℃下反应2~4h,得到改性重组人源化胶原蛋白;所述没食子酸酮酯为由以下醇酮化合物制备得到:1-羟基-3-癸酮、1-羟基-6-十四酮、1-羟基-4-十二酮、1-羟基-3-壬酮、7-羟基-2,4-庚二酮或6-羟基-2,4-己二酮;所述重组人源化胶原蛋白和没食子酸酮酯的投料质量比例为(10~30):1,其中重组人源化胶原蛋白以干基计算。
2.根据权利要求1所述的一种改性重组人源化胶原蛋白的制备方法,其特征在于,所述重组人源化胶原蛋白选自I型、II型、III型蛋白中的一种或组合。
3.一种改性重组人源化胶原蛋白,其特征在于,所述改性重组人源化胶原蛋白是根据权利要求1或权利要求2所述的制备方法制备得到。
4.根据权利要求3所述的一种改性重组人源化胶原蛋白在制备***敷料中的应用。
5.根据权利要求4所述的一种改性重组人源化胶原蛋白在制备***敷料中的应用,其特征在于,所述***敷料按质量分数计算,包括以下组分:改性重组人源化胶原蛋白、凝胶基质、增稠剂、防腐剂、保湿剂、pH调节剂和水。
6.根据权利要求5所述的一种改性重组人源化胶原蛋白在制备***敷料中的应用,其特征在于,所述***敷料制备步骤如下:先将凝胶基质、保湿剂和增稠剂溶解到纯水中,搅拌均匀,然后加入用0.22μm的膜过滤过的改性重组人源化胶原蛋白,继续搅拌,得到均匀体系,再加入防腐剂,然后用纯水将余量补足,搅拌均匀,然后加入pH调节剂调节pH值至3.5~4.2,即得成品。
7.根据权利要求5或6所述的一种改性重组人源化胶原蛋白在制备***敷料中的应用,其特征在于,所述凝胶基质选自卡波姆、黄原胶、海藻酸盐、透明质酸、泊洛沙姆中的一种或多种。
8.根据权利要求5或6所述的一种改性重组人源化胶原蛋白在制备***敷料中的应用,其特征在于,所述增稠剂剂选自羧甲基纤维素钠、羟乙基纤维素、羟丙基纤维素中的一种或多种。
9.根据权利要求5或6所述的一种改性重组人源化胶原蛋白在制备***敷料中的应用,其特征在于,所述防腐剂选自为尼泊金乙酯、苯氧乙醇中的一种或多种。
10.根据权利要求5或6所述的一种改性重组人源化胶原蛋白在制备***敷料中的应用,其特征在于,所述保湿剂选自透明质酸、甘油、丙二醇中的一种或多种。
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014129289A (ja) * | 2012-12-28 | 2014-07-10 | Uha Mikakuto Co Ltd | ガレート型カテキン含有化粧料 |
CN109567213A (zh) * | 2018-12-29 | 2019-04-05 | 安徽草珊瑚生物科技有限公司 | 一种复合胶原蛋白肽粉 |
CN110885467A (zh) * | 2019-11-25 | 2020-03-17 | 江苏大学 | 一种没食子酸和超声辅助金枪鱼皮蛋白-糖膜的制备方法 |
JP2021166494A (ja) * | 2020-04-10 | 2021-10-21 | 株式会社ファンケル | コラーゲン受容体産生促進用組成物 |
CN113559323A (zh) * | 2021-07-31 | 2021-10-29 | 福建省博特生物科技有限公司 | 一种负载没食子酸胶原蛋白可注射水凝胶的制备方法及水凝胶的应用 |
CN115068594A (zh) * | 2022-06-20 | 2022-09-20 | 四川大学 | 一种基于重组人源化胶原蛋白的可注射心衰治疗水凝胶及其制备方法 |
CN116391022A (zh) * | 2020-10-21 | 2023-07-04 | 弗门尼舍有限公司 | 改善的赋予新鲜度的组合物 |
-
2023
- 2023-12-01 CN CN202311631888.4A patent/CN117327171B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014129289A (ja) * | 2012-12-28 | 2014-07-10 | Uha Mikakuto Co Ltd | ガレート型カテキン含有化粧料 |
CN109567213A (zh) * | 2018-12-29 | 2019-04-05 | 安徽草珊瑚生物科技有限公司 | 一种复合胶原蛋白肽粉 |
CN110885467A (zh) * | 2019-11-25 | 2020-03-17 | 江苏大学 | 一种没食子酸和超声辅助金枪鱼皮蛋白-糖膜的制备方法 |
JP2021166494A (ja) * | 2020-04-10 | 2021-10-21 | 株式会社ファンケル | コラーゲン受容体産生促進用組成物 |
CN116391022A (zh) * | 2020-10-21 | 2023-07-04 | 弗门尼舍有限公司 | 改善的赋予新鲜度的组合物 |
CN113559323A (zh) * | 2021-07-31 | 2021-10-29 | 福建省博特生物科技有限公司 | 一种负载没食子酸胶原蛋白可注射水凝胶的制备方法及水凝胶的应用 |
CN115068594A (zh) * | 2022-06-20 | 2022-09-20 | 四川大学 | 一种基于重组人源化胶原蛋白的可注射心衰治疗水凝胶及其制备方法 |
Non-Patent Citations (1)
Title |
---|
没食子酸对胶原蛋白膜的改性研究;胡可欣;李国英;;皮革科学与工程(第04期);1-6 * |
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