CN111420036A - 含有i型胶原和丹参提取物的复合物及制备和应用 - Google Patents
含有i型胶原和丹参提取物的复合物及制备和应用 Download PDFInfo
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- CN111420036A CN111420036A CN202010361886.8A CN202010361886A CN111420036A CN 111420036 A CN111420036 A CN 111420036A CN 202010361886 A CN202010361886 A CN 202010361886A CN 111420036 A CN111420036 A CN 111420036A
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Abstract
本发明提供了一种含有I型胶原和丹参提取物的复合物,其特征在于,该复合物包括I型胶原、丹参提取物和平衡物质;其中,所述平衡物质包括NaH2PO4‑Na2HPO4体系、Tris‑HCl体系、Tris‑马来酸体系或HEPES体系,以及包括NaCl和/或KCl;该复合物的pH为6‑8。本发明还提供了所述复合物的制备方法及其用途,并提供了一种预防或缓解或治疗眼疾的产品。本发明提供的复合物,对于预防或治疗与视疲劳、干眼症、近视与老花等眼疾非常有效;此外,该复合物还可以用于各类型的皮肤损伤修复,还能够增加皮肤弹性,减少色素沉着、皱纹等,具有一定的美容效果。本发明提供的含有I型胶原和丹参提取物的复合物的制备方法非常简单,成本低廉,易于大规模生产。
Description
技术领域
本发明属于生物技术领域,具体涉及一种含有I型胶原和丹参提取物的复合物及其制备方法和应用。
背景技术
科技的迅猛发展改变了人们的生产和生活方式,尤其是现代信息的传播方式、通讯电子设备的使用,使得电脑、智能手机、互联网等成为日常工作和生活的必需品。在更便捷地获取信息,为生活和工作带来巨大便利的同时,给眼睛健康带来了严重的问题,这必将造成全社会的重大公共卫生危机。长时间的注视屏幕加上不正确、不卫生的用眼习惯,造成严重的视觉健康问题,使近视、视疲劳及干眼症等各种眼科疾病大幅度上升。
目前,缓解干眼与眼疲劳的产品通常为人工泪液等滴眼剂和眼膏。人工泪液等滴眼剂虽然对缓解干眼与疲劳等症状有一定功效,但作用时间短而容易流失;眼膏附着时间较长但有异物感,有不适感。
有效避免永久性视力损害、缓解视疲劳的产品开发,成为维护视觉健康、提高生活质量最迫切的需求。
胶原蛋白是细胞外基质中最主要的结构蛋白,具有许多生物活性与生物学功能,例如参与细胞增殖、迁移与分化。利用胶原的生物活性,目前,许多产品中都包含有胶原。然而,胶原的等电点在pH7.4左右,当溶液接近中性时胶原不稳定,容易析出。因此,在现有的产品中,胶原都是以偏酸性(pH4-6)的环境加入。然而,中性环境是细胞代谢最适的pH,因此,如何使胶原稳定溶解于中性环境中,从而能够在中性条件下使用胶原,是急需解决的一个问题。
发明内容
为了解决现有技术中的上述问题,本发明提供了一种含有I型胶原和丹参提取物的复合物,该复合物能够预防或治疗与视疲劳、干眼症、近视和老花等相关的眼疾。
因此,一方面,本发明提供了一种含有I型胶原和丹参提取物的复合物,其特征在于,该复合物包括I型胶原、丹参提取物和平衡物质;其中,所述平衡物质包括NaH2PO4-Na2HPO4体系、Tris-HCl体系、Tris-马来酸体系或HEPES体系,以及包括NaCl和/或KCl;该复合物的pH为6-8。
另一方面,本发明提供了上述复合物在制备用于预防或治疗眼疾的药物中的用途;或者所述复合物用于预防或缓解眼疾的化妆品。
另一方面,本发明提供了一种预防或缓解或治疗眼疾的产品,其中,该产品含有本发明提供的所述复合物。
另一方面,本发明提供了一种含有I型胶原和丹参提取物的复合物的方法,其中,该方法包括以下步骤:
a.配制平衡物质:向水中加入NaH2PO4-Na2HPO4体系的物质、Tris-HCl体系的物质、Tris-马来酸体系的物质或HEPES体系的物质,以及NaCl和/或KCl;
b.向所述平衡物质中加入I型胶原和丹参提取物,获得所述复合物,该复合物的pH为6-8。
本发明提供的含有I型胶原和丹参提取物的复合物,在生理pH值范围内,I型胶原能够稳定存在,长时间放置也不会出现沉淀;而且,在优选的实施方式中,该复合物的渗透压和张力均适于生理体系。此外,本发明提供的含有I型胶原蛋白和丹参提取物的复合物对于视疲劳、干眼症、近视与老花等眼疾非常有效;此外,该复合物还能够修复各类型的皮肤损伤,并且还能够增加皮肤弹性,减少色素沉着、皱纹,具有一定的美容效果。
本发明提供的含有I型胶原和丹参提取物的复合物的制备方法非常简单,成本低廉,易于大规模生产。
附图说明
图1A:为对照组、添加CI组、添加CI和SAC组的Col1-α1的mRNA表达的图;图1B为对照组、添加CI组、添加CI和SAC组的Col3-α1的mRNA表达的图;图1C为对照组、添加CI组、添加CI和SAC组的过氧化氢酶的mRNA表达的图;图1D为对照组、添加CI组、添加CI和SAC组的核纤层蛋白B1的mRNA表达图;图1E为对照组、添加CI组、添加CI和SAC组的LINE1的mRNA表达图;1F为对照组、添加CI组、添加CI和SAC组的Ifn1的mRNA表达的图。
具体实施方式
本发明提供了一种含有I型胶原和丹参提取物的复合物,其特征在于,该复合物包括I型胶原、丹参提取物和平衡物质;其中,所述平衡物质包括NaH2PO4-Na2HPO4体系、Tris-HCl体系、Tris-马来酸体系或HEPES体系,以及包括NaCl和/或KCl;该复合物的pH为6-8。
为了获得等渗与等张,优选地,NaCl和/或KCl的浓度为0.2-0.9重量%。
发明人发现,在本发明提供的含有I型胶原和丹参提取物的复合物,平衡物质不仅能够提供生理环境下的pH值,具有增溶与助溶作用,有助于该复合体系的稳定;同时能有效维持液体等张及渗透压,非常适于生理体系的直接应用。
我国有丰富的植物资源,传统中医药学应用已经过千百年的锤炼,在数千年临床实践中积累了丰富经验,为从天然药源中寻找新的安全有效的眼科疾病治疗药物提供了宝贵的线索。中药丹参为唇形科植物(Salvia miltiorrhiza Bge)的干燥根和根茎,味苦,性微寒,归心、肝经,首载于《神农本草经》,列为上品生药;在《本草纲目》中有“一味丹参功同四物汤”之记载,具有祛瘀止疼、活血痛经等功效。现代医学研究证实其通过改善血液流变性、血流动力及改善微循环等途径发挥活血化瘀的作用,主治胸痹心痛、癥瘕积聚、月经不调等,既可单方又可复方,从古至今发挥重要的临床治疗作用。
本申请的发明人发现I型胶原蛋白与丹参提取物协同作用,可以激活和改善眼部及环眼部细胞代谢活性,形成护眼产品。经初步试验发现:该复合物能够减缓和防止视疲劳、干眼症。近视与老花等眼疾通常在视疲劳、干眼症情况下加重,因此,减缓和防止视疲劳、干眼症将有利于改善近视与老花。
为了对视疲劳、干眼症具有更好的效果,在一种优选的实施方式中,所述丹参提取物中的活性成分(SAC)的浓度为7-100μg/ml;优选为,所述活性成分的浓度为10-50μg/ml。
为了减少所述复合物中丹参的其它成分,优选地,所述丹参提取物中活性成分的含量为50-99重量%,更优选为60-90重量%。
为了进一步保持丹参有效成分的活性以及使药物进行缓释,所述丹参提取物以微囊的形式存在于所述复合物中。微囊可以用现有技术制备,优选地,以壳聚糖、明胶、海藻酸盐及甲基纤维素等水溶性材料为囊材进行包裹制备微囊,其中囊心为丹参提取物。微囊可以克服丹参水溶性有效成份容易吸潮活性下降的问题,并起到缓释作用。
为了制备的便利,优选地,所述丹参提取物为水溶性提取物,其活性成分可以包括酚酸类活性物质。
发明人发现本发明的复合物,可以显著促进人表皮细胞(Hacat)分泌Ⅰ型和Ⅲ型胶原的基因表达;激活抗氧化系统,显著提高过氧化氢酶的基因表达,以增加氧自由基的清除能力;刺激表皮抗衰老关键基因层粘连蛋白B1高效表达,同时有效降低细胞衰老因子L1(LINE1)的表达(甚至低至检测不到),双向拮抗衰老退变;阻断炎症因子IFN-1(干扰素I)的表达,抑制炎症发生及其引起后续细胞凋亡。
为了获得更好的皮肤修复作用和美容效果,优选地,所述I型胶原的浓度为0.5-8mg/ml;更优选地,所述I型胶原的浓度为1-5mg/ml。
为了获得更好的保湿和美容效果,优选地,本发明的复合物还可以包括透明质酸;优选地,透明质酸的浓度为0.1-8mg/ml,更优选为0.5-5mg/ml。
为了提供更接近生理体系的复合物,在本发明的一个优选实施方式中,所述平衡物质包括NaH2PO4-Na2HPO4体系和NaCl;其中,NaH2PO4的浓度为0.04-0.7重量%、Na2HPO4的浓度为0.1-0.9重量%、NaCl的浓度为0.3-0.8重量%;优选地,NaH2PO4的浓度为0.08-0.64重量%、NaH2PO4的浓度为0.2-0.8重量%、NaCl的浓度为0.4-0.5重量%。
为了进一步提高本发明提供的含有I型胶原和透明质酸的复合物的稳定性,其中,所述平衡物质还含有葡萄糖、1,3丙二醇和吐温80中的一种或几种;优选地,所述葡萄糖的浓度为0.1-10重量%,所述1,3丙二醇的浓度为0.5-3mg/ml,所述吐温80的浓度为0.1-1mg/ml。
优选地,所述复合物还含有凝胶基质辅料;优选地,所述凝胶基质辅料的浓度为0.1-3重量%。所述凝胶基质包括但不限于纤维素衍生物、卡波姆、海藻酸盐、西黄蓍胶和明胶中的一种或几种。
本发明提供的复合物可以用于在制备用于预防或治疗眼疾的药物中的用途;或者所述复合物用于预防或缓解眼疾的化妆品;优选地,所述眼疾为视疲劳、干眼症、近视和老花中的一种或几种症状。
本发明提供的复合物还可以用于修复皮肤损伤。所述皮肤损伤包括:各种外界因素导致的创伤:例如,烧伤、烫伤、冻伤、晒伤、割伤等导致的皮肤损伤;压疮,例如,褥疮,防护用品压力性损伤;疤痕;皮肤过敏,例如,季节性的皮肤过敏;红肿;痤疮;潮红;激光治疗手术后的红肿与炎症。
本发明还提供一种预防或缓解或治疗眼疾的产品,其中,该产品含有本发明提供的复合物;优选地,所述眼疾为视疲劳、干眼症、近视和老花中的一种或几种症状。
所述产品可以为药物,根据实际情况需要还可以包括其它成分,例如抗生素。所述药物复合物还可以包括药学上可接受的载体。
药学上可接受的载体可以为,例如填充剂、芳香剂、调味剂、着色剂、润湿剂、赋形剂、表面活性剂。
本发明提供的产品可根据本领域已知的方法制备,制成适于人或动物使用的任何剂型。
本发明提供的含有I型胶原和丹参提取物的复合物在所述产品中的含量通常为0.1-95重量%,或可根据不同的应用由本领域技术人员进行相应调整。
本发明提供的产品可以为凝胶剂,贴敷料(例如,用无纺布、敷垫作为承托)等。
损伤产品可以为化妆品,所述化妆品可以为洗面奶,面霜,乳液,面膜(可以为含有无纺布或棉纤维面膜,或者为不含无纺布的面膜),或贴敷料等。
本发明提供的含有I型胶原和丹参提取物的复合物在所述化妆品中的含量通常为0.1-95重量%,或可根据不同的应用由本领域技术人员进行相应调整。
本发明还提供一种制备权利要求1所述的复合物的方法,其中,该方法包括以下步骤:
a.配制平衡物质:向水中加入NaH2PO4-Na2HPO4体系的物质、Tris-HCl体系的物质、Tris-马来酸体系的物质或HEPES体系的物质,以及NaCl和/或KCl;
b.向所述平衡物质中加入I型胶原和丹参提取物,获得所述复合物,该复合物的pH为6-8。
优选地,NaCl和/或KCl的浓度为0.2-0.9重量%。
在一种优选的实施方式中,所述丹参提取物中的活性成分的浓度为7-100μg/ml;优选为,所述活性成分的浓度为10-50μg/ml。
优选地,所述丹参提取物中活性成分的含量为50-99重量%,更优选为60-90重量%。
优选地,所述丹参提取物以微囊的形式添加到所述复合物中。微囊可以用现有技术制备,优选地,以壳聚糖、明胶、海藻酸盐及甲基纤维素等水溶性材料为囊材进行包裹制备微囊,其中囊心为丹参提取物。
优选地,所述I型胶原的添加浓度为0.5-8mg/ml;更优选地,所述I型胶原的添加浓度为1-5mg/ml。
在本发明的一个优选实施方式中,所述平衡物质包括NaH2PO4-Na2HPO4体系和NaCl;其中,NaH2PO4的浓度为0.04-0.7重量%、Na2HPO4的浓度为0.1-0.9重量%、NaCl的浓度为0.3-0.8重量%;优选地,NaH2PO4的浓度为0.08-0.64重量%、NaH2PO4的浓度为0.2-0.8重量%、NaCl的浓度为0.4-0.5重量%。
优选地,所述平衡物质还含有葡萄糖、1,3丙二醇和吐温80中的一种或几种;优选地,所述葡萄糖的浓度为0.1-10重量%,所述1,3丙二醇的浓度为0.5-3mg/ml,所述吐温80的浓度为0.1-1mg/ml。
优选地,向所述复合物中加入凝胶基质辅料;优选地,所述凝胶基质辅料的浓度为0.1-3重量%。所述凝胶基质包括但不限于纤维素衍生物(例如,羟甲基丙基纤维素)、卡波姆、海藻酸盐、西黄蓍胶和明胶中的一种或几种。
I型胶原和丹参提取物都可以商购获得。
实施例1:胶原蛋白的制备及物理化学性能检测
前处理:牛筋腱切碎,清洗,生理盐水洗涤后包封,经Co60消毒。余下步骤在无菌条件下进行。
制备高纯度的Ⅰ型胶原溶液:牛筋腱碎粒中加入0.5M醋酸适量,并加入胃蛋白酶(每20g牛筋腱加入1克胃蛋白酶),酶解30小时,15mmol/L EDTA终止酶解。高速离心收取上清液为Ⅰ型胶原溶液,沉淀可以重复此步骤继续提取胶原。此过程在4℃以下进行。
纯化:按体积1:1加入胶原溶液及10%NaCl盐析,静置过夜。离心获取沉淀,用0.5M醋酸溶解,去离子水中透析,得到高纯度的Ⅰ型胶原溶液(8mg/ml以上)。
标准对照产品:SigmaI型胶原产品C9301,称取0.6mg,加入0.5M乙酸120μL缓慢震荡使其溶解,配置成5mg/ml溶液。取10μL加入平衡液中备用。
Ⅰ型胶原蛋白质量检测(参照中国医药行业标准YY0954-2015附录B杂蛋白检测方法):采用Tris-甘氨酸不连续分离系统,配制6%分离胶、5%浓缩胶。取浓度为10mg/ml的Ⅰ型胶原溶液及Sigma标准对照液,各10μl,加入90μL双蒸水稀释后,按比例加入2x Loadingbuffer混匀,沸水浴10min;12000x g,5min离心取上清液15μL进行SDS-PAGE电泳。条件:60V,20min;120V,1h 25min(仪器型号:Bio-Rad,PowerPac Universal),用考马斯亮蓝R-250染色液对凝胶进行染色,扫描凝胶成像(Umax,PowerLook,2100XL-USB),得到高纯度特征性I型胶原条带。
取2μL样品,使用超微量核酸蛋白检测仪(Nanodrop 2000)扫描,波长200nm-800nm,胶原特征峰230nm读数分别为1.397,符合Ⅰ型胶原蛋白特征要求。
采用实施例1制备的I型胶原和进行后续实验。
实施例2:低浓度I型胶原液的制备(pH 6)
a.配制平衡物质(95ml):在去离子水中加入NaH2PO4 0.643g,Na2HPO4 0.189g;NaCl 0.47g,葡萄糖0.1g,1,3丙二醇0.5ml,吐温80 0.1ml。
b.量取10mg/ml I型胶原液5ml。
c.混合步骤a、b,获得含有Ⅰ型胶原的凝胶液100ml,该凝胶液的pH 6,NaH2PO4的浓度约为0.643重量%,Na2HPO4的浓度约为0.189重量%,NaCl的浓度约为0.47重量%,葡萄糖的浓度约为0.1重量%,1,3丙二醇的浓度为0.5ml/ml,吐温80的浓度为0.1ml/ml,Ⅰ型胶原的浓度为1mg/ml。
实施例3:中等浓度I型胶原液的制备(pH7)
a.配制平衡(70ml)物质:在去离子水中加入NaH2PO40.322g,Na2HPO40.566g,NaCl0.45g,葡萄糖2g,1,3丙二醇1.5ml,吐温80 0.5ml。
b.量取10mg/ml的Ⅰ型胶原液30ml。
c.混合步骤a、b,获得含有Ⅰ型胶原的凝胶液100ml,该凝胶液的pH为7,NaH2PO4的浓度约为0.322重量%;Na2HPO4的浓度约为0.566重量%,NaCl的浓度约为0.44重量%,葡萄糖的浓度约为5重量%,1,3丙二醇的浓度为1.5ml/ml,吐温80的浓度为0.5ml/ml,Ⅰ型胶原的浓度为3mg/ml。
实施例4:高浓度I型胶原液的制备(pH 8)
a.配制平衡物质(50ml):在去离子水中加入NaH2PO4的浓度为0.04g;Na2HPO40.897g;NaCl 0.42g,葡萄糖4g,1,3丙二醇3ml,吐温80 1ml。
b.量取10mg/ml的Ⅰ型胶原液50ml。
c.混合步骤a、b,获得含有Ⅰ型胶原的凝胶液100ml,该凝胶液的pH为8,NaH2PO4的浓度约为0.04重量%;Na2HPO4的浓度约为0.897重量%;NaCl的浓度约为0.42重量%,葡萄糖的浓度约为4重量%,1,3丙二醇的浓度为3ml/ml,吐温80的浓度为1ml/ml,Ⅰ型胶原的浓度为5mg/ml。
对比例1:制备低浓度的胶原混合液
用实施例1方法制备Ⅰ型胶原溶液,用PBS配制浓度为0.5mg/ml,获得Ⅰ型胶原混合液(有沉淀生成),pH 6。
对比例2:制备中等浓度的胶原混合液
用实施例1方法制备Ⅰ型胶原溶液,用PBS配制浓度为3mg/ml,获得Ⅰ型胶原混合液(有沉淀生成)pH 7。
对比例3:制备高浓度的胶原混合液
用实施例1方法制备Ⅰ型胶原溶液,用PBS配制浓度为5mg/ml,获得Ⅰ型胶原混合液(有沉淀生成),pH 8。
性能测试1:Ⅰ型胶原液稳定性实验(pH 6)
a.实施例2配制的胶原液及对比例1配制的低浓度混合液,分别于4℃,12000x g,10min离心,吸取上清液备用。分别各取2μl样品检测,使用超微量核酸蛋白检测仪(Nanodrop 2000)波长200nm-800nm连续扫描,并对Ⅰ型胶原特征峰230nm进行读数,发现混合液上清液中230nm特征峰基本消失;而本发明凝胶液离心前后特征峰无显著变化。
b.羟脯氨酸法测定胶原浓度(参照中国医药行业标准YY0954-2015附录A胶原蛋白检测方法):按照南京建成羟脯胺酸检测试剂盒(A030-2-1)说明书操作。吸取a处理的两种样品的离心上清液0.25ml,加入试剂盒中的水解液0.5ml混匀,沸水浴水解20min;调节pH至6.5,按操作步骤离心后取上清液,于波长550nm下检测吸光度,并于标准品进行比较,计算出I型胶原蛋白含量(表1)。
c.通过特征峰扫描及羟脯氨酸法测定胶原浓度,结果显示混合液组离心后与离心前比较,胶原浓度有显著下降;而平衡液组离心前后胶原浓度均无显著性差异,表明本发明平衡液(pH 6)有良好的稳定性。
表1 pH6低浓度I型胶原液稳定性实验蛋白检测分析
注:**有显著性差异
性能测试2:Ⅰ型胶原液稳定性实验(pH7)
a.实施例3配制的胶原液及对比例2配制的中浓度混合液,分别于4℃,12000xg,10min离心,吸取上清液备用。分别各取2μl样品检测,使用超微量核酸蛋白检测仪(Nanodrop 2000)波长200nm-800nm连续扫描,并对I型胶原特征峰230nm进行读数,发现混合液上清液中特征峰230nm基本消失;而本发明复合凝胶液离心前后特征峰无显著变化。
余下步骤与性能测试1中b、c相同,结果表明本发明胶原平衡液(pH7)有良好的稳定性(表2)。
表2 pH7中等浓度I型胶原液稳定性实验蛋白检测分析
注:**有显著性差异
性能测试3:Ⅰ型胶原液稳定性实验(pH8)
a.实施例4配制的胶原液及对比例3配制的高浓度混合液,分别于4℃,12000xg,10min离心,吸取上清液备用。分别各取2μl样品检测,使用超微量核酸蛋白检测仪(Nanodrop 2000)波长200nm-800nm连续扫描,并对I型胶原特征峰230nm进行读数,发现混合液上清液中特征峰230nm基本消失;而本发明复合凝胶液离心前后特征峰无显著变化。
余下步骤与性能测试1中b、c相同,结果表明本发明胶原液(pH8)有良好的稳定性及促进相溶的作用(表3)。
表3 pH8高浓度I型胶原稳定性实验蛋白检测分析
注:**有显著性差异
性能测试4:Ⅰ型胶原液长期存放稳定性检测
性能测试2步骤a的方法配制平衡物。
制备4组胶原液,配制方法、平衡物质组份同实施例3:使得其中Ⅰ型胶原的浓度分别为1mg/ml、2mg/ml、3mg/ml、4mg/ml,pH7。
制备的Ⅰ型胶原液存放在8℃冰箱中,分别在1、5、10、20周后,同样用羟脯氨酸法测定胶原的浓度,结果显示放置20周后Ⅰ型胶原的含量与pH均无明显变化,表明本发明胶原液具有良好的稳定性。
表4 pH7 I型胶原液长期存放稳定性实验
性能测试5:本发明复合物对表皮细胞表型的影响
I型胶原包被培养板:将实施例3制备的I型胶原液(pH 7)加入24孔培养板中,每孔0.3ml,于37℃培养箱中干燥2天成膜。临用前添加DMEM-F12培养基1ml平衡备用。
表皮细胞(人角质形成细胞,Hacat细胞株)表型调控实验:
实验组分为:不加药的对照组、I型胶原(CI)处理组,和I型胶原(CI)+SAC处理组,共三组。Hacat细胞接种于24孔板中,其中,I型胶原(CI)处理组,和I型胶原(CI)+SAC处理组的细胞接种于上述I型胶原包被的24孔板中;细胞接种密度每孔为3万,加入含有10%血清和1%双抗的MEM培养基,丹参提取物用PBS溶解,按照丹酚酸B有效浓度为20μg/ml的量添加;三种样品于37℃,5%CO2条件下培养24小时。
荧光定量qPCR检测,分析测试5种基因分别为Col1-α1、Col3-α1、过氧化氢酶、层粘连蛋白B1、LINE1与INF-1:同时以GAPDH检测作为内参基因进行表达量差异分析(图示)。结果显示:①促进细胞增殖分化的正向表型基因Col1-α1的表达:与对照组相比,I型胶原(CI)组和I型胶原(CI)+SAC组的Col1-α1的表达均有显著上调,差异有显著性;其中I型胶原(CI)+SAC组显示最佳效果(图1A)。②为皮肤提供弹性与韧性、缓解皮肤老化的基因Col3的表达:与对照组相比,I型胶原(CI)组和I型胶原(CI)+SAC组的Col3的表达均有显著上调,差异极显著;其中I型胶原(CI)+SAC组显示最佳效果(图1B)。③活化能增加氧自由基的清除能力的关键因子过氧化氢酶的基因表达的表达:在加入生长调控因素后随着代谢活性的增加而呈现显著上调趋势,与对照组相比,I型胶原(CI)组和I型胶原(CI)+SAC组的过氧化氢酶的表达均有显著上调,差异极显著;其中I型胶原(CI)+SAC组显示最佳效果(图1C);④活化表皮细胞抗衰老的关键基因层粘连蛋白B1,在加入生长调控因素后随着代谢活性的增加而呈现高效表达,与对照组相比,I型胶原(CI)组和I型胶原(CI)+SAC组的层粘连蛋白B1的表达均有显著上调,差异极显著;其中I型胶原(CI)+SAC组显示最佳效果(图1D);⑤有效降低表皮细胞衰老的关键因子LINE1表达,与对照组相比,I型胶原(CI)组和I型胶原(CI)+SAC组的LINE1的表达均有显著下调,差异极显著;其中两个加药组LINE1的表达低至几乎检测不到(图1E);⑥阻断炎症因子IFN-1(干扰素I)的表达,与对照组相比,I型胶原(CI)组和I型胶原(CI)+SAC组的IFN-1的表达均有显著下调,差异极显著;其中两个加药组IFN-1的表达低至几乎检测不到(图1F)。上述结果表明本发明提供的复合物具有改善人表皮细胞生长微环境,显著上调抗衰老关键基因、强烈抑制衰老的关键因子LINE1基因达到双向拮抗表皮细胞的衰老退变、保护细胞代谢平衡等多重调节作用。
以下实验将检测本发明提供的含有I型胶原和SAC的复合物在改善视觉疲劳和眼干等方面的效果。
以下实验采用的复合物通过以下方法制备:在实施例3制备的I型胶原液中加入丹参提取物(用PBS溶解),按照丹酚酸B有效浓度为20μg/ml的量添加,混合均匀后,将99重量%的该混合物与1重量%的羟甲基丙基纤维素混合均匀。
入选观察对象情况及分组(40名志愿者):包括长时间使用电脑的人员(每天6小时或以上),手术医生,长时间使用手机者(每天6小时或以上);随机分为实验与对照两组;实验组使用上述复合物,对照组使用珍珠明目滴眼液滴眼。
使用方法:临睡前用常规办法流水清洁脸部皮肤,擦干。实验组用上述复合物均匀涂抹环眼部皮肤;对照组使用珍珠明目滴眼液滴眼(天龙制药有限公司)。
评判方法:按照眼睛眼干、涩、痒、肿胀、视力模糊等症状情况评分,5分最严重,0为消失。
结果:第二天,实验组所有志愿者眼睛眼干、涩、痒、肿胀、视力模糊等症状明显消失,全天感觉明显改善;对照组上述症状清晨有所减退,但午后又重新出现,如下表:
胶原/SAC护眼凝胶疗效对照表
Claims (10)
1.一种含有I型胶原和丹参提取物的复合物,其特征在于,该复合物包括I型胶原、丹参提取物和平衡物质;其中,所述平衡物质包括NaH2PO4-Na2HPO4体系、Tris-HCl体系、Tris-马来酸体系或HEPES体系;该复合物的pH为6-8,以及包括NaCl和/或KCl;该复合物的pH为6-8;优选地,NaCl和/或KCl的浓度为0.2-0.9重量%。
2.根据权利要求1所述的复合物,其中,所述丹参提取物中活性成分的浓度为7-100μg/ml,优选地,所述活性成分的浓度为10-50μg/ml。
3.根据权利要求1所述的复合物,其中,所述丹参提取物中活性成分的含量为50-99重量%,优选为60-90重量%;优选地,所述丹参提取物以微胶囊的形式存在于所述复合物中。
4.根据权利要求3所述的复合物,其中,所述I型胶原的浓度为0.5-8mg/ml;优选地,所述I型胶原的浓度为1-5mg/ml。
5.根据权利要求1所述的复合物,其中,所述平衡物质包括NaH2PO4-Na2HPO4体系和NaCl;其中,NaH2PO4的浓度为0.04-0.7重量%、Na2HPO4的浓度为0.1-0.9重量%、NaCl的浓度为0.3-0.8重量%;优选地,NaH2PO4的浓度为0.08-0.64重量%、NaH2PO4的浓度为0.2-0.8重量%、NaCl的浓度为0.4-0.5重量%。
6.根据权利要求1所述的复合物,其中,所述平衡物质还含有葡萄糖、1,3丙二醇,和吐温80中的一种或几种;优选地,所述平衡物质含有葡萄糖、1,3丙二醇和吐温;优选地,所述葡萄糖的浓度为0.1-10重量%,所述1,3丙二醇的浓度为0.5-3mg/ml,所述吐温80的浓度为0.1-1mg/ml。
7.根据权利要求1-6所述的复合物,其中,该复合物还含有凝胶基质辅料;优选地,所述凝胶基质辅料的浓度0.1-3重量%。
8.根据权利要求1-7中任意一项所述的复合物在制备用于预防或治疗眼疾的药物中的用途;或者所述复合物用于预防或缓解眼疾的化妆品;优选地,所述眼疾为视疲劳、干眼症、近视和老花中的一种或几种症状。
9.一种预防或缓解或治疗眼疾的产品,其中,该产品含有权利要求1-7中任意一项所述的复合物;优选地,所述眼疾为视疲劳、干眼症、近视和老花中的一种或几种症状。
10.一种制备权利要求1所述的复合物的方法,其中,该方法包括以下步骤:
a.配制平衡物质:向水中加入NaH2PO4-Na2HPO4体系的物质、Tris-HCl体系的物质、Tris-马来酸体系的物质或HEPES体系的物质,以及NaCl和/或KCl;
b.向所述平衡物质中加入I型胶原和丹参提取物,获得所述复合物,该复合物的pH为6-8。
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