CN116549432B - 用于治疗皮损伤的scm-198凝胶及scm-198凝胶制备方法 - Google Patents
用于治疗皮损伤的scm-198凝胶及scm-198凝胶制备方法 Download PDFInfo
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- Cosmetics (AREA)
Abstract
本发明涉及治疗皮损伤药物制剂领域,公开了一种用于治疗皮损伤的SCM‑198凝胶及SCM‑198凝胶制备方法,SCM‑198凝胶包括以下重量百分比的原料:SCM‑198粉末0.1%‑5%、凝胶基底0.5‑5%、酸碱度调节剂0.01%‑1%、促溶剂0.20%‑1.5%、防腐剂0.01%‑0.05%、保湿剂1%‑10%和去离子水。本申请的发明人在前期研究工作中发现SCM‑198在抑制炎症、防治缺血性中风、防治帕金森病、治疗II型糖尿。本申请还提供了三种用于治疗皮损伤的SCM‑198凝胶制备方法。本发明提供了一种促进皮肤慢性病、提高胰岛素敏感性、治疗血管性痴呆、治疗抑郁症、改善不孕症妊娠结局等方面的用途,SCM‑198用于皮肤慢性创面的治疗药物的用途创面愈合的SCM‑198凝胶剂,能够促进创面愈合,抗炎消肿,修复皮肤,预防瘢痕和促进毛发生长的作用。
Description
技术领域
本发明涉及SCM-198凝胶配方用来制作的化妆品、保健品、药物组合物对皮肤慢性创面的治疗作用。组合物可以包含促皮肤创面愈合的SCM-198等任意比例的混合物。特别涉及一种用于治疗皮损伤的SCM-198凝胶及SCM-19凝胶制备方法。
背景技术
皮肤创面的愈合过程包括三个连续的阶段:炎症、增殖和再生。烧伤后,皮肤组织的破坏导致微循环功能障碍,产生氧化应激,并在受伤部位释放促炎细胞因子。在创面愈合过程中,往往伴随纤维增生性疾病,如增生性瘢痕和疤痕疙瘩等。目前对于疤痕的预防和治疗还没有令人满意的策略或方法。现临床使用较广泛的碱性成纤维细胞生长因子凝胶,是生物蛋白类药品,成本高,制作工艺较复杂。
发明内容
有鉴于此,有必要提供一种用于治疗皮损伤的SCM-198凝胶及SCM-198凝胶制备方法。SCM-198,又称为益母草碱,中药益母草的主要提取物之一,其化学名称为4-胍基-1-丁香酸丁酯。
一种用于治疗皮损伤的SCM-198凝胶,包括以下重量百分比的原料:SCM-198粉末0.1%-5%、凝胶基底0.5-5%、酸碱度调节剂0.01%-1%、促溶剂0.20%-1.5%、防腐剂0.01%-0.05%、保湿剂1%-10%和去离子水。
优选的,重量百分比为0.5-5%的凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠0.01%-1%,或三乙醇胺0.01%-1%;防腐剂为羟苯乙酯0.01%-0.05%;保湿剂为甘油1%-10%;促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-20 0.1%-0.5%、Tween-800.1%-0.5%。
优选的,用于治疗皮损伤的SCM-198凝胶还包括以下附加成分的任意一种或任意组合或全部:水、药剂、螯合剂、防腐剂、增稠剂、含硅酮的化合物、精油、结构剂、维生素、药物成分、或抗氧化剂、或非天然存在的化合物、或这些成分的任意组合或这些成分混合物。在某些方面,组合物可以包括在前句中确定的附加成分的至少2种、3种、4种、5种、6种、7种、8种、9种、10种或全部。这些附加成分的非限制性实例在整个说明书中确定,并通过引用并入本部分。这些成分的量可以为以组合物重量或体积计的0.0001%至99.9%,或本说明书其它部分所公开的任何整数或范围内,其通过引用并入本段;
用于治疗皮损伤的SCM-198凝胶还包含一种或更多种载体或稀释剂。这些载体/稀释剂可以是佐剂、赋形剂或载剂,如防腐剂、填充剂、崩解剂、润湿剂、乳化剂、助悬剂、甜味剂、调味剂、香料、抗菌剂、抗真菌剂、润滑剂、维生素、聚合物、含硅氧烷的化合物、精油、结构剂和分散剂。每种载体在与制剂的其他成分相容并且不损害对象的意义上是可接受的。
一种用于治疗皮损伤的SCM-198凝胶的制备方法,包括以下步骤:
步骤一,溶胀溶胶基底;
步骤二,将酸碱度调节剂与去离子水相溶,制备成酸度调节溶液;
步骤三,将酸度调节溶液分批次加入已溶胀好的溶胀溶胶基底当中,边加边搅拌,既得凝胶基底;
步骤四,称取SCM-198粉末于烧杯中;
步骤五,在烧杯中加入促溶剂,然后加入磁子,开启磁力搅拌;
步骤六,将步骤五中的溶液分批加入到凝胶基底中,并不断搅拌至均匀;
步骤七,在步骤六得到的凝胶中加入保湿剂,并补充去离子水至预计凝胶药剂的总克数,不断搅拌至凝胶均匀,既得SCM-198凝胶。
优选的,步骤五中的促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-20 0.1%-0.5%、Tween-80 0.1%-0.5%;在烧杯中加入羧甲基纤维素钠溶液,然后加入磁子,开启磁力搅拌,形成磁力体系;然后在磁力体系中加入Tween-20、Tween-80及防腐剂继续搅拌至溶解,然后进入步骤六中,分批加入到凝胶基底中;凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠或三乙醇胺;防腐剂为羟苯乙酯;保湿剂为甘油。
优选的,步骤一中,称取适量卡波姆940粉末放入容器中,放入磁子,加入适量去离子水,在水浴中,加热搅拌使卡波姆940粉末充分溶胀,水浴的温度为45℃以上,较佳温度为50℃;步骤二,将氢氧化钠溶于适量去离子水;步骤三,将步骤二中的氢氧化钠溶液分批次加入步骤一中已溶胀好的卡波姆溶液当中,已溶胀好的卡波姆溶液的pH=5,边加边搅拌,卡波姆溶液逐渐透明、粘稠成形,最终pH=7,既得凝胶基底;步骤四,称取适量SCM-198粉末于烧杯中。
一种用于治疗皮损伤的SCM-198凝胶的制备方法,包括以下步骤:
步骤S1,称取适量SCM-198粉末及适量凝胶基底粉末于烧杯中;
步骤S2,在烧杯中加入适量促溶剂,加入磁子,水浴加热,开启磁力搅拌直至固体溶解且凝胶基底粉末充分溶胀;
步骤S3,将酸碱度调节剂溶于适量去离子水中,形成酸碱度调节剂溶液;
步骤S4,将酸碱度调节溶液分批次加入步骤S2中已溶胀好的溶液当中,边加边搅拌,混合体系逐渐粘稠成形;
步骤S5,将适量促溶剂及防腐剂溶于适量去离子水中;
步骤S6,将步骤S5中溶于分批加入步骤S4凝胶中,并不断搅拌;
步骤S7,在步骤S6得到的凝胶中加入保湿剂,并补充去离子水至预计凝胶药剂的总克数,不断搅拌至凝胶均匀,既得SCM-198凝胶。
优选的,凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠或三乙醇胺;防腐剂为羟苯乙酯;保湿剂为甘油;
促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-20 0.1%-0.5%、Tween-800.1%-0.5%,步骤S2,在烧杯中加入适量0.5%羧甲基纤维素钠溶液,加入磁子,水浴加热,开启磁力搅拌直至固体溶解且卡波姆940粉末充分溶胀;步骤S5中,将适量Tween-20、Tween-80及羟苯乙酯溶于适量去离子水中。
一种用于治疗皮损伤的SCM-198凝胶的制备方法,包括以下步骤:
步骤A1:称取适量凝胶基底粉末放入容器中,放入磁子,加入适量去离子水,在水浴中,加热搅拌使凝胶基底粉末充分溶胀;水浴的温度高于45℃,较佳温度为50℃;
步骤A2:将酸碱度调节剂溶于适量去离子水,形成酸碱度调节溶液;
步骤A3:将酸碱度调节溶液分批次加入步骤A1中已溶胀好的溶液当中,边加边搅拌,溶液逐渐透明、粘稠成形,加入适量去离子水,继续搅拌,既得凝胶基底;
步骤A4:称量空烧杯质量,称取适量SCM-198粉末于烧杯中;
步骤A5:在步骤A4的烧杯中加入适量0.5%促溶剂溶液,加入磁子,开启磁力搅拌,形成磁力体系;
步骤A6:在步骤A5的磁力体系中加入适量促溶剂及防腐剂继续搅拌至溶解;
步骤A7:称量步骤A6中烧杯总质量,减去空烧杯质量,得到溶液总质量;
步骤A8:用预计SCM-198凝胶总质量减去溶液总质量和所需保湿剂质量,即为所需凝胶基底质量;
步骤A9:称取步骤A8中所需的凝胶基底,将步骤A6中溶液分批加入到凝胶基底中,不断搅拌,加入保湿剂,并不断搅拌至凝胶颜色均匀且不分层,既得SCM-198凝胶。
优选的,凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠或三乙醇胺;防腐剂为羟苯乙酯;保湿剂为甘油;
促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-20 0.1%-0.5%、Tween-800.1%-0.5%;步骤A5中,在步骤A4的烧杯中加入适量0.5%羧甲基纤维素钠溶液,加入磁子,开启磁力搅拌,形成磁力体系;步骤A6中,在步骤A5的磁力体系中加入适量Tween-20、Tween-80及羟苯乙酯继续搅拌至溶解。
本申请的发明人在前期研究工作中发现SCM-198在抑制炎症、防治缺血性中风、防治帕金森病、治疗II型糖尿病、提高胰岛素敏感性、治疗血管性痴呆、治疗抑郁症、改善不孕症妊娠结局等方面的用途,SCM-198用于皮肤慢性创面的治疗药物的用途。本发明提供了一种促进皮肤慢性创面愈合的SCM-198凝胶剂,能够促进创面愈合,抗炎消肿,修复皮肤,预防瘢痕和促进毛发生长的作用。
附图说明
图1是本发明中使用的有效活性成分SCM-198的化学结构式;
图2是本发明提供的实例一中各组大鼠的创面愈合效果示意图;
图3是本发明提供的实例一中各组大鼠的创面愈合率统计图;
图4是本发明提供的实例二中各组大鼠的创面愈合效果示意图;
图5是本发明提供的实例二中各组大鼠的表面创面愈合率统计图;
图6是本发明提供的实例二中各组大鼠创面H&E染色放大10倍,标尺为1mm;
图7是本发明提供的实例二中各组大鼠第23天创面组织面积和表皮厚度统计图;
图8是本发明提供的实例二中各组大鼠mRNA表达统计图;
具体实施方式
为了使本发明技术方案更容易理解,现结合附图采用具体实施例的方式,对本发明的技术方案进行清晰、完整的描述。
用于治疗皮损伤的SCM-198凝胶,包括以下重量百分比的原料:SCM-198粉末0.1%-5%、凝胶基底0.5-5%、酸碱度调节剂0.01%-1%、促溶剂0.205-1.5%、防腐剂0.01%-0.05%、保湿剂1%-10%和去离子水。重量百分比为0.5-5%的凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠0.01%-1%,或三乙醇胺0.01%-1%;防腐剂为羟苯乙酯0.01%-0.05%;保湿剂为甘油1%-10%;促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-20 0.1%-0.5%、Tween-80 0.1%-0.5%。
用于治疗皮损伤的SCM-198凝胶还包括以下附加成分的任意一种或任意组合或全部:水、药剂、螯合剂、防腐剂、增稠剂、含硅酮的化合物、精油、结构剂、维生素、药物成分、或抗氧化剂、或非天然存在的化合物、或这些成分的任意组合或这些成分混合物。在某些方面,组合物可以包括在前句中确定的附加成分的至少2种、3种、4种、5种、6种、7种、8种、9种、10种或全部。这些附加成分的非限制性实例在整个说明书中确定,并通过引用并入本部分。这些成分的量可以为以组合物重量或体积计的0.0001%至99.9%,或本说明书其它部分所公开的任何整数或范围内,其通过引用并入本段;用于治疗皮损伤的SCM-198凝胶还包含一种或更多种载体或稀释剂。这些载体/稀释剂可以是佐剂、赋形剂或载剂,如防腐剂、填充剂、崩解剂、润湿剂、乳化剂、助悬剂、甜味剂、调味剂、香料、抗菌剂、抗真菌剂、润滑剂、维生素、聚合物、含硅氧烷的化合物、精油、结构剂和分散剂。每种载体在与制剂的其他成分相容并且不损害对象的意义上是可接受的。
所述用于治疗皮损伤的SCM-198凝胶通过以下三种方法获得:
方法一:
步骤1:称取适量卡波姆940粉末放入容器中,放入磁子,加入适量去离子水,在温度为45℃以上的水浴中,较佳温度为50℃,加热搅拌使卡波姆940粉末充分溶胀;
步骤2:将氢氧化钠溶于适量去离子水;
步骤3:将步骤2中的氢氧化钠溶液分批次加入步骤1中已溶胀好的卡波姆溶液,pH=5当中,边加边搅拌,卡波姆溶液逐渐透明、粘稠成形,最终pH=7,既得凝胶基底;
步骤4:称取适量SCM-198粉末于烧杯中;
步骤5:在步骤4的烧杯中加入适量0.5%羧甲基纤维素钠溶液,加入磁子,开启磁力搅拌;
步骤6:在步骤5的体系中加入适量Tween-20、Tween-80及羟苯乙酯继续搅拌至溶解;
步骤7:将步骤6溶液分批加入到步骤3得到的基底中,并不断搅拌至均匀;
步骤8:在步骤7得到的凝胶中加入甘油等保湿剂,并补充去离子水至预计凝胶药剂的总克数,不断搅拌至凝胶均匀,既得SCM-198凝胶。
方法二:
步骤S1:称取适量SCM-198粉末及适量卡波姆940粉末于烧杯中;
步骤S2:在步骤S1的烧杯中加入适量0.5%羧甲基纤维素钠溶液,加入磁子,水浴加热,开启磁力搅拌直至固体溶解且卡波姆940粉末充分溶胀;
步骤S3:将氢氧化钠溶于适量去离子水;
步骤S4:将步骤S3中的氢氧化钠溶液分批次加入步骤2中已溶胀好的卡波姆溶液当中,边加边搅拌,混合体系逐渐粘稠成形;
步骤S5:将适量Tween-20、Tween-80及羟苯乙酯溶于适量去离子水中;
步骤S6:将步骤S5中溶于分批加入步骤4凝胶中,并不断搅拌;
步骤S7:在步骤S6得到的凝胶中加入甘油等保湿剂,并补充去离子水至预计凝胶药剂的总克数,不断搅拌至凝胶均匀,既得SCM-198凝胶。
方法三:
步骤A1:称取适量卡波姆940粉末放入容器中,放入磁子,加入适量去离子水,在温度为45℃以上水浴中,较佳温度可为50℃,加热搅拌使卡波姆940粉末充分溶胀;
步骤A2:将氢氧化钠溶于适量去离子水;
步骤A3:将步骤A2中的氢氧化钠溶液分批次加入步骤A1中已溶胀好的卡波姆溶液pH=5当中,边加边搅拌,卡波姆溶液逐渐透明、粘稠成形,最终pH=7,加入适量去离子水,继续搅拌,既得凝胶基底;
步骤A4:称量空烧杯质量。称取适量SCM-198粉末于烧杯中;
步骤A5:在步骤A4的烧杯中加入适量0.5%羧甲基纤维素钠溶液,加入磁子,开启磁力搅拌;
步骤A6:在步骤5的体系中加入适量Tween-20、Tween-80及羟苯乙酯继续搅拌至溶解;
步骤A7:称量步骤A6中烧杯总质量,减去空烧杯质量,得到溶液总质量;
步骤A8:用预计SCM-198凝胶总质量减去溶液总质量和所需保湿剂质量,即为所需凝胶基底质量;
步骤A9:称取步骤A8中所需的凝胶基底,将步骤A6中溶液分批加入到凝胶基底中,不断搅拌。加入甘油等保湿剂,并不断搅拌至凝胶颜色均匀且不分层,既得SCM-198凝胶。
本申请提供以下两种实施例:
实施例一,SCM-198凝胶剂的配制及浓度选择
1不同浓度SCM凝胶剂配制
1)称取卡波姆940(150mg)于20mL玻璃反应瓶中,加入适量的去离子水,在50℃水浴中,磁力搅拌,使卡波姆粉末充分溶胀。用广普试纸测量卡波姆溶液pH值为5。将氢氧化钠颗粒(60mg)溶于蒸馏水中,分批加入卡波姆溶液中,不断搅拌,直到pH为7,得到无色透明的凝胶基底。向基底中分批次加入0.5%羧甲基纤维素钠溶液(8mL),Tween-20(75mg),Tween-80(75mg)和750mL甘油不断搅拌至混匀。加蒸馏水至整个体系15g,搅拌至颜色均匀不分层,既得到无色透明的空白凝胶剂。
2)称取卡波姆940(150mg)于20mL玻璃反应瓶中,加入适量的去离子水,在50℃水浴中,磁力搅拌,使卡波姆粉末充分溶胀。用广普试纸测量卡波姆溶液pH值为5。将氢氧化钠颗粒(60mg)溶于蒸馏水中,分批加入卡波姆溶液中,不断搅拌,直到pH为7,得到无色透明的凝胶基底。另取小烧杯,放入SCM粉末(75mg),加入0.5%羧甲基纤维素钠溶液(8mL),Tween-20(75mg),Tween-80(75mg),水浴加热促进溶解,得淡黄色溶液。将SCM-198溶液,分批次加进已成型的凝胶基底中,并不断搅拌。在凝胶中加入750mL甘油,加蒸馏水至整个体系15g,不断搅拌至其颜色均匀不分层,既得质量浓度(w/w)为0.5% SCM-198凝胶,SCM-198的化学结构式如图1所示。
用同样的方法配制得到质量浓度(w/w)为1%及1.5% SCM-198凝胶剂。
2动物实验
5只大鼠随机分成空白对照组、SCM-198两组,空白对照组2只,SCM-198组3只。每只均进行烫伤造模,对SD大鼠进行腹腔注射2%(w/w)戊巴比妥钠溶液进行麻醉。每只大鼠都使用脱毛膏进行背部脱毛。将黄铜片在酒精灯外焰中加热1分钟后,置于大鼠已脱毛的背部10秒进行烫伤。空白对照组每只动物背部烫伤两个创面,从上到下编号依次为A、B,A涂抹无负载药物的凝胶基底,B不给药自然恢复。SCM-198组每只动物背部烫伤四个创面,从上到下编号为A、B、C和D。创面A涂抹0.5% SCM-198凝胶剂,B为涂抹1%SCM-198凝胶剂,C为1.5%SCM-198凝胶剂,D不做处理。每天给药一次并拍照,统计创面大小。
3结果
在受烫伤后的第三天,直接受热皮肤周边会有明显的创面扩张,因此愈合率出现负值。请同时参阅图2及图3,从创面愈合情况如图2和创面愈合率如表1和图3来看,高浓度对创面愈合的促进作用更加明显。在后期的治疗中,可以选择高浓度进行治疗。(Dn天愈合率=(D0天面积-Dn天面积)÷D0天面积×100%)
表1实施例一中各组大鼠在不同天数的创面愈合率统计
实施例二:SCM-198促进烫伤创面愈合的药效学研究
仪器与材料
仪器与药品,见表1:
表2药品列表
实验动物
雄性Sprague-Dawley(SD)大鼠(250-300g,6-8周),SPF(Specific pathogenFree)级别,从香港中文大学进购,饲养于澳门科技大学药学院动物房。大鼠在具有25℃恒温和湿度控制的动物设施中饲养。实验期间自由饮水进食,实验前适应性喂养14天。澳门市政局动物伦理及使用委员会批准了这里描述的所有研究(批准号:AL010/DICV/SIS/2018)。
实验部分
凝胶剂配制
1、凝胶基底(30g):将卡波姆940(304.7mg)放入50mL玻璃样品瓶,加入17mL去离子水,在50℃水浴中,磁力搅拌,使卡波姆充分溶胀,用广普试纸测pH为5。将氢氧化钠(121mg)溶于3mL去离子水,分批次加入已溶胀好的卡波姆溶液当中,并不断搅拌,至pH为7。向其中加入Tween-80(88mg)、Tween-20(60mg)、甘油(1502.1mg),不断搅拌。补充去离子水至30g,充分搅拌得到透明粘稠凝胶基底。
2、1.5%(w/w)SCM凝胶剂(40g):将卡波姆940(400.2mg)放入50mL玻璃样品瓶,加入20mL去离子水,在50℃水浴中,磁力搅拌,使卡波姆充分溶胀,用广普试纸测pH为5。将氢氧化钠(160mg)溶于1mL去离子水,分批次加入已溶胀好的卡波姆溶液当中,并边加边搅拌,卡波姆溶液逐渐透明、粘稠成形,最终pH=7,得到凝胶基底。称取SCM粉末(600.4mg)于小烧杯,放入磁子,加入0.5%羧甲基纤维素钠10mL,Tween-80(84.6mg)、Tween-20(66mg),在50℃水浴中,磁力搅拌,得SCM溶液。将SCM溶液分批加入凝胶基底中,并不断搅拌至充分混匀。再加入甘油(2005mg),补充去离子水至40g,不断搅拌至充分混匀,既得到1.5%(w/w)SCM凝胶剂。
SD大鼠烫伤造模
1、SD大鼠分组及给药方式
表3实例二中动物实验分组及给药方式
注:①重组牛碱性成纤维细胞生长因子
2、烫伤造模
将大鼠随机分成5个组,除对照组外,其他4组均进行烫伤造模。对SD大鼠进行腹腔注射2%(w/w)戊巴比妥钠溶液进行麻醉。每只大鼠都使用脱毛膏进行背部脱毛。将黄铜片在酒精灯外焰中加热1分钟后,置于大鼠已脱毛的背部10秒进行烫伤。拍照后,实验组涂抹凝胶剂进行治疗。
3、组织学检测
分别在给药第11天及最后一天(第23天)时,每组取5只老鼠进行安乐死,取背部创面所在的皮肤,泡在4%多聚甲醛中。在蜡块中包埋,制作切片,用苏木精和伊红(H&E)染色。
4、RNA提取及实时荧光定量PCR分析
将存放于-80℃冰箱中的皮肤组织取出,每个皮肤组织称取50-100g用来提取总RNA。使用北京索莱宝科技有限公司“总RNA提取试剂盒”,提取皮肤组织中总RNA。使用北京康为世纪生物科技有限公司“HiFiScript gDNA Removal cDNA Synthesis Kit”对RNA进行逆转录。使用北京全式金生物技术股份有限公司“Perfect Green qPCR SuperMix(+DyeII)”通过实时荧光定量PCR(qPCR)测量靶基因的表达。通过ViiA□7Real-Time PCR System(Applied Biosystems)进行qPCR,在95℃初始变性10分钟,然后在95℃变性30秒并在60℃退火30秒,进行55个循环,72℃30秒。以β-actin为内参基因,采用2-△△Ct法分析靶基因的相对表达。用于qPCR的基因特异性引物序列如表4:
表4实例二中qPRC所用的大鼠基因及特异性引物序列
数据处理
用ImageJ软件对创面面积进行统计,并计算创面愈合率(Dn天愈合率=(D0天面积-Dn天面积)÷D0天面积×100%)。用GraphPad Prism软件做统计图并进行单因素方差分析。所有数据表示为“平均值±标准差”,显著值P<0.05记为“*”或“#”,P<0.01记为“**”或“##”,P<0.001记为“***”或“###”,P<0.0001记为“****”或“####”。
结果
实验结果证明,SCM凝胶对皮肤烫伤有治疗效果。从图4可以看出,SCM组从第8天开始创面周边炎症减轻,红肿开始消退,而bFGF组仍有较重的炎症,如图4所示。“SCM-198”组的创面愈合率高于“不给药模型”和“空白凝胶基底”组,且具有显著性差异;与“bFGF”组愈合率无明显差异,如图5所示。病例组织学显示(如图6),在第23天时,给SCM-198和bFGF凝胶能够促进创面愈合,且“SCM-198”组出现更多毛囊等皮肤附属器,组织恢复更接近周边正常组织,胶原层厚度优于空白凝胶基底和bFGF组,表皮层完整,恢复良好。这提示,SCM-198有促进毛发生长的作用。对H&E切片中创面组织面积及表皮厚度(图6中黑色双向箭头代表表皮厚度)进行统计,如图7所示给SCM-198的组创面面积最小;表皮厚度最接近正常组小于“bFGF”组,且有显著性差异,更接近于正常组。图7A中,与“不给药模型”的对比差异用“*”表示,与“blank”的对比差异用“#”表示,与“SCM-198”的对比差异用“%”表示;图7B中,与“不给药模型”的对比差异用“*”表示,与“正常组”的对比差异用“#”表示,与“SCM-198”的对比差异用“%”表示。这些结果提示SCM-198能显著促进创面愈合。
表5实例二中各组大鼠伤口愈合率(平均值)
发明人对SCM-198的分子机理进行研究,qPCR结果显示(如图8),在愈合前期,给SCM-198凝胶能够促进血管内皮生长因子(VEGF)的表达,且与“bFGF”组无显著性差异;在愈合后期,“SCM-198”组的促炎因子IL-1β、IL-6的mRNA表达水平均低于“bFGF”组,且有显著性差异,这说明SCM-198在促进创面愈合的同时能够有效抑制炎症。另一方面,“SCM-1981.5%”组胶原蛋白I型(Col Iα1)的mRNA表达要低于“bFGF”组,但高于“不给药模型”组,胶原蛋白的表达会为细胞生长提供合适的环境,但过高表达会导致瘢痕的产生,这提示SCM-198凝胶在促进创面愈合的同时,能够改善瘢痕。bFGF凝胶是市售成熟的凝胶药物,已经广泛应用于临床上的小型创面。我们的数据说明,SCM-198在促进创面愈合方面有着不输于bFGF的效果,且具有抗炎、促毛发生长作用,功能更加丰富。
应当注意,在此所述的实施例仅为本发明的部分实施例,而非本发明的全部实现方式,所述实施例只有示例性,其作用只在于提供理解本发明内容更为直观明了的方式,而不是对本发明所述技术方案的限制。在不脱离本发明构思的前提下,所有本领域普通技术人员没有做出创造性劳动就能想到的其它实施方式,及其它对本发明技术方案的简单替换和各种变化,都属于本发明的保护范围。
Claims (9)
1.一种用于治疗皮损伤的SCM-198凝胶,其特征在于:用于治疗皮损伤的SCM-198凝胶包括以下重量百分比的原料:SCM-198粉末0.1%-5%、凝胶基底0.5-5%、酸碱度调节剂0.01%-1%、促溶剂0.20%-1.5%、防腐剂0.01%-0.05%、保湿剂1%-10%和去离子水;
SCM-198的化学结构式为:
用于治疗皮损伤的SCM-198凝胶的制备方法包括以下步骤:
步骤一,溶胀溶胶基底;
步骤二,将酸碱度调节剂与去离子水相溶,制备成酸度调节溶液;
步骤三,将酸度调节溶液分批次加入已溶胀好的溶胀溶胶基底当中,边加边搅拌,即得凝胶基底;
步骤四,称取SCM-198粉末于烧杯中;
步骤五,在烧杯中加入促溶剂,然后加入磁子,开启磁力搅拌;
步骤六,将步骤五中的溶液分批加入到凝胶基底中,并不断搅拌至均匀;
步骤七,在步骤六得到的凝胶中加入保湿剂,并补充去离子水至预计凝胶药剂的总克数,不断搅拌至凝胶均匀,即得SCM-198凝胶;
步骤五中的促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-200.1%-0.5%、Tween-800.1%-0.5%;在烧杯中加入羧甲基纤维素钠溶液,然后加入磁子,开启磁力搅拌,形成磁力体系;然后在磁力体系中加入Tween-20、Tween-80及防腐剂继续搅拌至溶解,然后进入步骤六中,分批加入到凝胶基底中;凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠或三乙醇胺;防腐剂为羟苯乙酯;保湿剂为甘油。
2.如权利要求1所述的用于治疗皮损伤的SCM-198凝胶,其特征在于:重量百分比为0.5-5%的凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠0.01%-1%,或三乙醇胺0.01%-1%;防腐剂为羟苯乙酯0.01%-0.05%;保湿剂为甘油1%-10%;促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-200.1%-0.5%、Tween-800.1%-0.5%。
3.如权利要求2所述的用于治疗皮损伤的SCM-198凝胶,其特征在于:用于治疗皮损伤的SCM-198凝胶还包括以下附加成分的任意一种或任意组合或全部:水、螯合剂、防腐剂、增稠剂、含硅酮的化合物、精油、维生素或非天然存在的化合物或这些成分的任意组合或这些成分混合物;用于治疗皮损伤的SCM-198凝胶还包含一种或更多种稀释剂。
4.一种如权利要求1所述的用于治疗皮损伤的SCM-198凝胶的制备方法,其特征在于:用于治疗皮损伤的SCM-198凝胶的制备方法包括以下步骤:
步骤一,溶胀溶胶基底;
步骤二,将酸碱度调节剂与去离子水相溶,制备成酸度调节溶液;
步骤三,将酸度调节溶液分批次加入已溶胀好的溶胀溶胶基底当中,边加边搅拌,即得凝胶基底;
步骤四,称取SCM-198粉末于烧杯中;
步骤五,在烧杯中加入促溶剂,然后加入磁子,开启磁力搅拌;
步骤六,将步骤五中的溶液分批加入到凝胶基底中,并不断搅拌至均匀;
步骤七,在步骤六得到的凝胶中加入保湿剂,并补充去离子水至预计凝胶药剂的总克数,不断搅拌至凝胶均匀,即得SCM-198凝胶;
步骤五中的促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-200.1%-0.5%、Tween-800.1%-0.5%;在烧杯中加入羧甲基纤维素钠溶液,然后加入磁子,开启磁力搅拌,形成磁力体系;然后在磁力体系中加入Tween-20、Tween-80及防腐剂继续搅拌至溶解,然后进入步骤六中,分批加入到凝胶基底中;凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠或三乙醇胺;防腐剂为羟苯乙酯;保湿剂为甘油;
SCM-198的化学结构式为:
5.如权利要求4所述的用于治疗皮损伤的SCM-198凝胶的制备方法,其特征在于:步骤一中,称取适量卡波姆940粉末放入容器中,放入磁子,加入适量去离子水,在水浴中,加热搅拌使卡波姆940粉末充分溶胀;步骤二,将氢氧化钠溶于适量去离子水;步骤三,将步骤二中的氢氧化钠溶液分批次加入步骤一中已溶胀好的卡波姆溶液当中,已溶胀好的卡波姆溶液的pH=5,边加边搅拌,卡波姆溶液逐渐透明、粘稠成形,最终pH=7,即得凝胶基底;步骤四,称取适量SCM-198粉末于烧杯中。
6.一种如权利要求1所述的用于治疗皮损伤的SCM-198凝胶的制备方法,其特征在于:用于治疗皮损伤的SCM-198凝胶的制备方法包括以下步骤:
步骤S1,称取适量SCM-198粉末及适量凝胶基底粉末于烧杯中;
步骤S2,在烧杯中加入适量促溶剂,加入磁子,水浴加热,开启磁力搅拌直至固体溶解且凝胶基底粉末充分溶胀;
步骤S3,将酸碱度调节剂溶于适量去离子水中,形成酸碱度调节剂溶液;
步骤S4,将酸碱度调节溶液分批次加入步骤S2中已溶胀好的溶液当中,边加边搅拌,混合体系逐渐粘稠成形;
步骤S5,将适量促溶剂及防腐剂溶于适量去离子水中;
步骤S6,将步骤S5中溶于分批加入步骤S4凝胶中,并不断搅拌;
步骤S7,在步骤S6得到的凝胶中加入保湿剂,并补充去离子水至预计凝胶药剂的总克数,不断搅拌至凝胶均匀,即得SCM-198凝胶;
SCM-198的化学结构式为:
7.如权利要求6所述的用于治疗皮损伤的SCM-198凝胶的制备方法,其特征在于:凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠或三乙醇胺;防腐剂为羟苯乙酯;保湿剂为甘油;
促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-200.1%-0.5%、Tween-800.1%-0.5%,步骤S2,在烧杯中加入适量0.5%羧甲基纤维素钠溶液,加入磁子,水浴加热,开启磁力搅拌直至固体溶解且卡波姆940粉末充分溶胀;步骤S5中,将适量Tween-20、Tween-80及羟苯乙酯溶于适量去离子水中。
8.一种如权利要求1所述的用于治疗皮损伤的SCM-198凝胶的制备方法,其特征在于:用于治疗皮损伤的SCM-198凝胶的制备方法包括以下步骤:
步骤A1:称取适量凝胶基底粉末放入容器中,放入磁子,加入适量去离子水,在水浴中,加热搅拌使凝胶基底粉末充分溶胀;
步骤A2:将酸碱度调节剂溶于适量去离子水,形成酸碱度调节溶液;
步骤A3:将酸碱度调节溶液分批次加入步骤A1中已溶胀好的溶液当中,边加边搅拌,溶液逐渐透明、粘稠成形,加入适量去离子水,继续搅拌,即得凝胶基底;
步骤A4:称量空烧杯质量,称取适量SCM-198粉末于烧杯中;
步骤A5:在步骤A4的烧杯中加入适量0.5%促溶剂溶液,加入磁子,开启磁力搅拌,形成磁力体系;
步骤A6:在步骤A5的磁力体系中加入适量促溶剂及防腐剂继续搅拌至溶解;
步骤A7:称量步骤A6中烧杯总质量,减去空烧杯质量,得到溶液总质量;
步骤A8:用预计SCM-198凝胶总质量减去溶液总质量和所需保湿剂质量,即为所需凝胶基底质量;
步骤A9:称取步骤A8中所需的凝胶基底,将步骤A6中溶液分批加入到凝胶基底中,不断搅拌,加入保湿剂,并不断搅拌至凝胶颜色均匀且不分层,即得SCM-198凝胶;
SCM-198的化学结构式为:
9.如权利要求8所述的用于治疗皮损伤的SCM-198凝胶的制备方法,其特征在于:凝胶基底为卡波姆940;酸碱度调节剂为氢氧化钠或三乙醇胺;防腐剂为羟苯乙酯;保湿剂为甘油;
促溶剂为:羧甲基纤维素钠0.05%-0.5%、Tween-200.1%-0.5%、Tween-800.1%-0.5%;步骤A5中,在步骤A4的烧杯中加入适量0.5%羧甲基纤维素钠溶液,加入磁子,开启磁力搅拌,形成磁力体系;步骤A6中,在步骤A5的磁力体系中加入适量Tween-20、Tween-80及羟苯乙酯继续搅拌至溶解。
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