CN117064788A - 一种口腔护理组合物及其应用 - Google Patents
一种口腔护理组合物及其应用 Download PDFInfo
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- CN117064788A CN117064788A CN202311255386.6A CN202311255386A CN117064788A CN 117064788 A CN117064788 A CN 117064788A CN 202311255386 A CN202311255386 A CN 202311255386A CN 117064788 A CN117064788 A CN 117064788A
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Abstract
本发明提供一种组合物及其应用,进一步涉及口腔护理组合物。本发明的口腔护理组合物包含抗菌肽6K‑F17、重组乳铁蛋白(又称为“融合因子”)和重组胶原蛋白(重组人源I型胶原蛋白,又称为“福活因子”)。三者组合使用时具有明显的活性,抑菌、除臭效果明显,且可显著缓解牙龈炎/牙周炎。
Description
技术领域
本发明涉及组合物及其应用,具体涉及口腔护理用组合物及其应用。
背景技术
口腔疾病虽然在很大程度上可以预防,但对许多国家构成重大卫生负担,影响人的一生,造成疼痛、不适、毁容甚至死亡。据估计,口腔疾病影响了近35亿人。在全球范围内,估计超过20亿人患有龋齿、牙周炎或牙龈炎,超过5亿儿童患有乳牙龋齿、牙龈炎。随着城市化的发展和生活条件的改变,全球主要口腔疾病的患病率继续增加。根据报道,未经治疗的龋齿(蛀牙)、牙龈炎是最常见的口腔健康问题。口腔问题的治疗费用昂贵,通常不被医保覆盖。大多数低收入和中等收入国家没有足够的服务来预防和治疗口腔健康状况。口腔疾病是由许多常见的一系列可改变的风险因素引起的,包括食用糖、吸烟、饮酒和卫生状况差,以及其潜在的社会和健康问题。
牙周(牙龈)疾病会影响牙齿周围和支撑牙齿的组织。这种疾病的特点是牙龈出血或肿胀(牙龈炎),疼痛,有时有口臭。在更严重的情况下,牙龈会从牙齿和支撑骨骼上脱落,导致牙齿松动,有时甚至脱落。牙周病的主要危险因素是口腔卫生差和吸烟。
牙龈卟啉单胞菌与牙周疾病的发生与发展密切相关,并在其中发挥非常关键的作用。据报道,牙龈卟啉单胞菌感染常被认为是牙周组织破坏的首要原因。
另外,经常发生的一种情况是,牙龈卟啉单胞菌等口腔菌降解含硫氨基酸产生硫化氢和甲基硫醇而导致口臭。
大多数口腔健康状况在很大程度上是可以预防的,并且可以在早期阶段得到治疗。口腔护理膏是最常用的口腔护理产品,被认为是所有收入群体的必需品。市面上有不同口味的口腔护理膏,以迎合消费者不同的喜好。此外,市面上还有各种类型的美白牙膏可供选择。但是目前许多此类产品抑菌、除臭效果并不好,对牙龈炎的预防效果也并不理想。
因此,对口臭、牙龈炎/牙周炎有效且安全的口腔护理产品仍存在迫切的需求。
发明内容
针对现有技术的不足,本发明的目的在于提供一种组合物及其应用,尤其提供一种护理效果好的口腔护理组合物及其应用。
发明人进行了深入研究后发现,抗菌肽6K-F17、序列如SEQ ID NO:2所示的重组乳铁蛋白、序列如SEQ ID NO:3所示的重组胶原蛋白组合使用,用于口腔护理时可产生优良的效果,能够有效抑菌、减少口臭、改善口腔炎症问题,且具有非常好的安全性。
抗菌肽6K-F17最早由Beaudoin等人公开(Activity of a novel antimicrobialpeptide against Pseudomonas aeruginosabiofilms.Sci Rep 8,14728(2018)),其具有一定的抗菌活性,同时对哺乳动物细胞几乎没有细胞毒性,实验显示在浓度达到500μg/mL时也不会对红细胞造成溶血。抗菌肽6K-F17为阳离子抗微生物肽,其通过插入细菌细胞膜而使其破坏,发挥抗菌作用。
发明人对牛乳铁蛋白截取N-端叶,得到截短体。然后与促穿膜域、促愈合域、促折叠域融合表达,得到具有抗菌、抗病毒活性的重组乳铁蛋白(SEQ ID NO:2),又称为融合因子。融合促穿膜域的目的在于提高蛋白在细胞膜上的穿透与锚定功能,可能有潜力促进乳铁蛋白肽段破坏细菌或者病毒的包膜,一方面物理穿孔,破坏细菌病毒膜结构,一方面乳铁蛋白肽段与膜内的细菌或病毒核酸或蛋白通过电荷吸附物理结合,诱导核酸或蛋白的空间变构,阻断其正常生物学功能,从而抑制细菌或病毒的增殖。另外尝试通过促折叠域提高蛋白正确折叠与可溶性,增强蛋白产量和溶解度。
重组人源I型胶原α1链蛋白的氨基酸序列如SEQ ID NO:3所示,又称为福活因子,其可能加速伤口愈合,降低炎症反应。
本发明的抗菌肽6K-F17、重组乳铁蛋白、重组胶原蛋白组合物存在协同作用,取得了意外的效果。
因此,本发明的第一方面提供一种组合物,其特征在于,所述组合物包含抗菌肽6K-F17、重组乳铁蛋白和重组胶原蛋白。
在本发明的一些实施方案中,所述重组乳铁蛋白的氨基酸序列如SEQ ID NO:2所示。
在本发明的一些实施方案中,所述重组胶原蛋白为重组人源I型胶原蛋白。在本发明的一些实施方案中,所述重组人源I型胶原蛋白为重组人源I型胶原α1链蛋白。在本发明的一些实施方案中,所述重组胶原蛋白为重组人源I型胶原α1链蛋白。进一步地,在本发明的一些实施方案中,所述重组胶原蛋白的氨基酸序列如SEQ ID NO:3所示。
在本发明的一些实施方案中,所述抗菌肽6K-F17与重组乳铁蛋白的重量比为0.3:1至2:1。
在本发明的一些实施方案中,所述抗菌肽6K-F17与重组胶原蛋白的重量比为0.15:1至1:1。
在本发明的一些实施方案中,所述抗菌肽6K-F17与重组乳铁蛋白的重量比为0.3:1至2:1,且所述抗菌肽6K-F17与重组胶原蛋白的重量比为0.15:1至1:1。
在一些实施方案中,所述组合物包含按重量计的抗菌肽6K-F170.3份至2份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
在一些实施方案中,所述组合物包含按重量计的抗菌肽6K-F170.3份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
在一些实施方案中,所述组合物包含按重量计的抗菌肽6K-F171份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
在一些实施方案中,所述组合物包含按重量计的抗菌肽6K-F172份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
在一些实施方案中,所述组合物为口腔护理组合物。
本发明的第二方面提供一种口腔护理产品,其特征在于,所述口腔护理产品包含如本发明任一项所述的组合物。
在一些实施方案中,所述口腔护理产品任选自口腔护理膏、口腔用凝胶、口腔喷雾剂、漱口液和口腔冲洗剂。
在一些实施方案中,所述口腔护理产品为口腔护理膏。在一些实施方案中,所述口腔护理产品为口腔护理凝胶。
在一些实施方案中,所述口腔护理产品还包含选自以下的任一种或更多种:
摩擦剂、保湿剂、溶剂、增稠剂、香料、赋形剂、甜味剂、pH调节剂、表面活性剂、防腐剂、乳化剂、发泡剂、增溶剂、着色剂、抗氧化剂、螯合剂、抗菌剂和抗炎症剂。
在一些实施方案中,所述口腔护理产品由以下组成:
2%重量份的抗菌肽6K-F17-重组乳铁蛋白-重组胶原蛋白组合物、40%重量份的磷酸氢钙二水合物、6%重量份的丙二醇、1%重量份的十二烷基硫酸钠、0.3%重量份的焦磷酸钠、0.3%重量份的羧甲基纤维素钠、0.3%重量份的黄原胶、15%重量份的山梨醇、0.15%重量份的尼泊金甲酯、0.05%重量份的糖精钠、余量的纯净水;
其中所述抗菌肽6K-F17-重组乳铁蛋白-重组胶原蛋白组合物包含按重量计的抗菌肽6K-F170.3份至2份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
在本发明的一些实施方案中,所述抗菌肽6K-F17-重组乳铁蛋白-重组胶原蛋白组合物包含按重量计的抗菌肽6K-F170.3份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
在本发明的一些实施方案中,所述抗菌肽6K-F17-重组乳铁蛋白-重组胶原蛋白组合物包含按重量计的抗菌肽6K-F171份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
在本发明的一些实施方案中,所述抗菌肽6K-F17-重组乳铁蛋白-重组胶原蛋白组合物包含按重量计的抗菌肽6K-F172份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
在本发明的一些实施方案中,所述重组乳铁蛋白的氨基酸序列如SEQ ID NO:2所示。
在本发明的一些实施方案中,所述重组胶原蛋白为重组人源I型胶原α1链蛋白。进一步地,在本发明的一些实施方案中,所述重组胶原蛋白的氨基酸序列如SEQ ID NO:3所示。
本发明的第三方面提供一种本发明任一项所述的组合物在抑制牙龈卟啉单胞菌或制备口腔护理产品中的应用。
在一些实施方案中,提供本发明任一项所述的组合物在抑制牙龈卟啉单胞菌中的应用。
在一些实施方案中,提供本发明任一项所述的组合物在制备口腔护理产品中的应用。
在一些实施方案中,所述口腔护理产品任选自口腔护理膏、口腔用凝胶、口腔喷雾剂、漱口液和口腔冲洗剂。
在一些实施方案中,所述口腔护理产品为口腔护理膏。在一些实施方案中,所述口腔护理产品为口腔护理凝胶。
本发明的第四方面提供一种根据本发明任一项所述的口腔护理产品的制备方法,其特征在于,所述制备方法包括以下步骤:
将本发明任一项所述的组合物与其它原料混合均匀,得到所述口腔护理产品。
在符合本领域常识的基础上,上述各优选条件,可任意组合,即得本发明各较佳实例。
本发明的技术效果:本发明抗菌肽6K-F17、序列如SEQ ID NO:2所示的重组乳铁蛋白、序列如SEQ ID NO:3所示的重组胶原蛋白三者的组合物(三联)具有明显的活性,效果优于各成分单独使用、或者两者复配使用的效果。三联复配时抑菌、除臭效果明显,且可显著缓解牙龈炎/牙周炎。
附图说明
图1为本发明组合物用于改善牙周炎/牙龈炎的动物体内测试结果。
具体实施方式
如本文所提到的术语“摩擦剂”,是指口腔可接受的任何摩擦剂,可选择摩擦剂的类型、粒度和量使得在正常使用组合物时牙釉质不被过度地磨损。合适的摩擦剂包括但不限于二氧化硅(呈硅胶、水合二氧化硅或沉淀二氧化硅形式)、氧化铝、不溶性磷酸盐、碳酸钙、树脂摩擦剂等。所述不溶性磷酸盐可以为正磷酸盐、聚偏磷酸盐和焦磷酸盐。非限制性示例包括磷酸氢钙二水合物、磷酸氢钙无水合物。
如本文所提到的术语“保湿剂”,其包括甘油、山梨醇、聚乙二醇、丙二醇等。
如本文所提到的术语“增稠剂”,其包括三类:有机合成胶,如羧甲基纤维素钠、羟乙基纤维素、卡波树脂等;天然植物胶,如黄原胶、改性瓜尔胶、卡拉胶等;无机胶,如增稠型二氧化硅、胶性硅酸镁铝等。
如本文所提到的术语“赋形剂”,其包括蔗糖、乳糖、淀粉、葡萄糖、结晶性纤维素、甘露醇、山梨醇、木糖醇、赤藻糖醇、异麦芽糖醇、异麦芽酮糖、麦芽糖醇、海藻糖、乳糖醇、乳果糖、还原淀粉糖、还原异麦芽寡糖、偶联糖、口香糖基料、阿拉伯胶、明胶、十六烷基甲基纤维素、轻质无水硅酸、铝酸镁、偏硅酸铝酸钙、碳酸氢钠、磷酸钙等。
如本文所提到的术语“甜味剂”,其包括异麦芽糖醇、天冬酰苯丙氨酸甲酯、糖精钠、乙酰舒泛钾、甜菊苷、新橙皮基二氢査耳酮、甘草甜素、紫苏、祝马丁、天冬氨酰苯基丙氨酰基甲基酯、ρ-甲氧基肉桂醛等。
如本文所提到的术语“pH调节剂”,其包括焦磷酸钠、柠檬酸、磷酸、泛酸、苹果酸、焦磷酸、乳酸、酒石酸、甘油磷酸、乙酸、硝酸、或磷酸氢二钠等。
如本文所提到的术语“发泡剂”,其包括十二烷基硫酸钠、月桂酰肌氨酸钠、烷基磺基琥珀酸钠、椰子油脂肪酸单甘油磺酸钠、α-烯烃磺酸钠、N-酰基谷氨酸盐等的N-酰基氨基酸盐、2-烷基-N-羧甲基-N-羟基乙基咪唑鎓甜菜碱、麦芽糖醇脂肪酸酯、蔗糖脂肪酸酯、聚甘油脂肪酸酯、脂肪酸二乙醇酰胺、聚氧乙烯脱水山梨糖醇单硬脂酸酯、聚氧乙烯固化蓖麻油、聚氧乙烯脂肪酸酯等。
如本文所提到的术语“表面活性剂”,其包括十二烷基硫酸钠、α-烯烃磺酸钠、十二烷基苯磺酸钠、月桂基磺基乙酸钠、N-月桂酰肌氨酸钠、N-酰基谷氨酸盐、蔗糖脂肪酸酯、聚氧乙烯固化蓖麻油、聚氧乙烯聚氧丙烯嵌段共聚物、烷基糖苷类、脱水山梨糖醇脂肪酸酯、聚氧乙烯脱水山梨糖醇脂肪酸酯、烷基二甲基氧化胺、月桂基乙醇酰胺、椰油酰基肌氨酸钠、N-月桂酰甲基牛磺酸钠等。
如本文所提到的术语“防腐剂”,其包括苯甲酸钠、尼泊金甲酯、氯己定、西吡氯铵、三氯新、尼泊金乙酯、氟化钠、单氟磷酸钠等。
说明书中所称三联即为三者复配(三种活性成分的组合),二联即为二者复配(两种活性成分的组合)。
下面通过实施例的方式进一步说明本发明,但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法,按照常规方法和条件,或按照商品说明书选择。除非特别说明,本发明所用试剂和原料均来源于市售。溶菌酶为鸡蛋白溶菌酶(aladdin,L105521),CAS号12650-88-3。
实施例1.抗菌肽6K-F17的制备
按文献方法(Activity of a novel antimicrobial peptide againstPseudomonas aeruginosabiofilms.Sci Rep 8,14728(2018))制备得到抗菌肽6K-F17。使用含0.1%TFA的乙腈在RP-HPLC柱上纯化,纯化后在乙醇-水混合溶剂中多次重结晶,真空干燥。ESI-MS显示为抗菌肽6K-F17,HPLC纯度95.9%。将其作为原料用于以下实施例。
实施例2.重组乳铁蛋白的制备
合成得到含重组乳铁蛋白的编码序列(通过ExpOptimizer在默认参数下进行了在线的密码子优化)的DNA片段,然后与pET28a(+)载体均使用BlpI和NcoI酶切,酶切产物通过T4DNA连接酶连接。反应液转化stbl3感受态,过夜培养,挑选阳性克隆测序鉴定。测序正确的阳性克隆培养后,提取得到重组乳铁蛋白的表达载体质粒(SEQ ID NO:1)。
载体质粒转化表达菌株E.coli BL21(DE3)。在含卡那霉素的LB培养液中37℃过夜培养。加IPTG至0.4mM,16℃诱导20h。离心收集菌体,加裂解液后超声破碎,离心获得含重组乳铁蛋白的上清液。0.45um滤膜过滤后使用Ni-IDA-SepharoseCl-6B层析纯化(Ni-IDAELution-Buffer洗脱)、然后使用RP-HPLC纯化(0.1%TFA-乙腈梯度洗脱),洗脱液冷冻干燥,得到HPLC纯度95.6%的重组乳铁蛋白(SEQ ID NO:2)。其在SDS-PAGE中呈现一条带。
实施例3.组合物的制备
按照专利CN109988234A的方法制备得到重组人源I型胶原α1链蛋白固体(SEQ IDNO:3),HPLC纯度95.0%。使用前述实施例的抗菌肽6K-F17、重组乳铁蛋白。
制备例1
按以下组成及配比(按质量计):抗菌肽6K-F171份、重组乳铁蛋白1份、重组人源I型胶原α1链蛋白2份;混合均匀得到口腔护理组合物1。
制备例2
按以下组成及配比(按质量计):溶菌酶1份、重组乳铁蛋白1份、重组人源I型胶原α1链蛋白2份;混合均匀得到口腔护理组合物2。
制备例3
按以下组成及配比(按质量计):抗菌肽6K-F171份、重组乳铁蛋白1份;混合均匀得到口腔护理组合物3。
制备例4
按以下组成及配比(按质量计):抗菌肽6K-F171份、重组人源I型胶原α1链蛋白2份;混合均匀得到口腔护理组合物4。
制备例5
按以下组成及配比(按质量计):重组乳铁蛋白1份、重组人源I型胶原α1链蛋白2份;混合均匀得到口腔护理组合物5。
制备例6
按以下组成及配比(按质量计):抗菌肽6K-F172份、重组乳铁蛋白1份、重组人源I型胶原α1链蛋白2份;混合均匀得到口腔护理组合物6。
制备例7
按以下组成及配比(按质量计):抗菌肽6K-F170.3份、重组乳铁蛋白1份、重组人源I型胶原α1链蛋白2份;混合均匀得到口腔护理组合物7。
制备例8
按以下组成及配比(按质量计):抗菌肽6K-F170.1份、重组乳铁蛋白1份、重组人源I型胶原α1链蛋白2份;混合均匀得到口腔护理组合物8。
制备例9
单独的抗菌肽6K-F17、溶菌酶、重组乳铁蛋白、重组人源I型胶原α1链蛋白分别称为口腔护理物9、口腔护理物10、口腔护理物11、口腔护理物12。
实施例4.口腔护理膏的制备
设以下组成及配比(按质量计):前述制备例中的口腔护理组合物1-8或口腔护理物9-12中任一种(2%)、磷酸氢钙二水合物(40%)、丙二醇(6%)、十二烷基硫酸钠(1%)、焦磷酸钠(0.3%)、羧甲基纤维素钠(0.3%)、黄原胶(0.3%)、山梨醇(15%)、尼泊金甲酯(0.15%)、糖精钠(0.05%)、纯净水(余量)。
按配方比例准确称量好各种原料备用。
将糖精钠、焦磷酸钠、尼泊金甲酯用热纯净水溶解,加入山梨醇。将羧甲基纤维素钠、黄原胶、丙二醇混合均匀。将磷酸氢钙二水合物、十二烷基硫酸钠混合均匀。开动制膏机,将上述预混料与制备例中的口腔护理组合物1-8或口腔护理物9-12中任一种混合均匀,得到成品膏体。将膏状物灌装到软管中,用封尾机封尾即得口腔护理膏。
由口腔护理组合物1-8分别制备得到口腔护理膏1-8,由口腔护理物9-12分别制备得到口腔护理膏9-12。
实施例5.除臭效果测试
向小瓶中加入10mL PBS磷酸盐缓冲液、牙龈卟啉单胞菌(ATCC 33277)菌液(OD值0.3)4mL、前述实施例的口腔护理组合物1-8或口腔护理物9-12中任一种的浓度300μg/mL的水溶液或充分分散的水悬浮液0.5mL(阴性对照组以0.5mL水代替),以及100mM的L-蛋氨酸水溶液0.25mL,混合均匀。将其在密封状态下37℃厌氧培养3小时。然后用气相色谱测定产生的甲基硫醇量。
以阴性对照组测得的甲基硫醇量定为100%,各实验组的甲基硫醇量相比阴性对照减少的比率为除臭率,即(阴性对照组-实验组)/阴性对照组×100%。
重复5次实验,结果取平均值。如表1所示。
表1.除臭率测试结果
抗菌肽6K-F17+重组乳铁蛋白+重组人源I型胶原α1链蛋白三联配方具有明显的除臭效果,三联配方(口腔护理组合物1、6、7)效果显著优于单独使用6K-F17或重组乳铁蛋白(P<0.05),优于6K-F17+重组人源I型胶原α1链蛋白二联方案(P<0.05)、优于重组乳铁蛋白+重组人源I型胶原α1链蛋白二联方案(P<0.05),且优于溶菌酶+重组乳铁蛋白+重组人源I型胶原α1链蛋白三联复配(P<0.05)。
实施例6.抑菌测试
将15mLBHI琼脂培养基加热至完全溶解,加入实施例3中的口腔护理组合物1/6/7/8或口腔护理物9中任一种的水溶液或充分分散的水悬浮液(阳性对照组加氯霉素水溶液,阴性对照组加水)1mL,混合均匀,使得口腔护理组合物或口腔护理物浓度为512μg/mL、256μg/mL、128μg/mL、64μg/mL、32μg/mL、16μg/mL、8μg/mL、4μg/mL、2μg/mL、1μg/mL、0.5μg/mL或0.25μg/mL。倾入灭过菌的培养皿中,室温冷却使琼脂凝固。接种10e7 CFU/mL的牙龈卟啉单胞菌(ATCC 33277)菌液1μL。37℃厌氧培养(10%CO2,10%H2,80%N2)24小时,最小抑菌浓度MIC定义为肉眼观测能够抑制细菌生长的最小药物浓度。
结果显示口腔护理组合物1/6/7/8具有明显的抑菌活性,优于单独的抗菌肽6K-F17(口腔护理物9)。
表2.抑菌测试结果
分组 | MIC(μg/mL) |
阳性对照 | 1 |
阴性对照 | 菌液生长且繁殖迅速 |
口腔护理组合物1 | 2 |
口腔护理组合物6 | 1 |
口腔护理组合物7 | 2 |
口腔护理组合物8 | 16 |
口腔护理物9 | 128 |
实施例7.改善牙龈炎效果测试
取健康、体重为8-10kg的成年比格犬,以2天为间隔口腔接种5次含10e10 CFU的牙龈卟啉单胞菌(ATCC 33277)的2%羧甲基纤维素悬浮液。继续喂养5天,得到患有牙周炎/牙龈炎的模型犬。
取模型犬(雌雄各半),将其随机分组,每组10只。实验组使用实施例4中口腔护理膏进行口腔日常护理,并评估其效果。阴性对照组同样使用口腔护理膏进行口腔日常护理,该口腔护理膏制备方法与实施例4相同,只是不含前述制备例中的口腔护理组合物或口腔护理物。每次取2g护理膏,使用牙刷均匀涂覆于受试犬的所有牙齿表面和根部,10分钟后将护理膏清除干净,尽量减少受试犬咽下的护理膏量。每日口腔护理2次。第7天时,观察视诊和牙龈出血情况判定牙龈指数(gingival index,GI),即Loe1H和Silness牙龈指数。
每只犬检查事先随机确定的8颗牙,每颗牙检查周围的牙龈,确定牙龈缘在近中、远中、颊侧、舌侧4个区域的情况,如下分为0-3级标准(0-3分)。每颗牙的记分为4个区域记分的平均值。每只受试犬的记分为全部受检牙记分的平均值。
0分—正常牙龈。
1分—轻度炎症:龈色轻微改变、轻度充血、用探针探不出血。
2分—中度炎症:牙龈出血、水肿、光滑、探之出血。
3分—重度炎症:牙龈充血、水肿、溃疡、有自发出血。
观察发现所有受试犬的口腔粘膜都没有明显的进一步损伤,表明不会对口腔黏膜造成刺激或毒性作用。
实验结果如图1所示。可以看出,抗菌肽6K-F17、重组乳铁蛋白、重组人源I型胶原α1链蛋白三者复配后(护理膏1/6/7/8)具有显著活性,降低牙龈指数,即显著缓解牙龈炎。单独使用抗菌肽6K-F17、重组乳铁蛋白、重组人源I型胶原α1链蛋白或溶菌酶时,对牙龈炎的改善作用较弱,但抗菌肽6K-F17、重组乳铁蛋白、重组人源I型胶原α1链蛋白三者合用时效果显著提高(P<0.01),且护理膏1、6、7远优于溶菌酶、重组乳铁蛋白、重组人源I型胶原α1链蛋白三者复配(溶菌酶三联)的效果(P<0.01)。因此取得了预料不到的技术效果。
另外,护理膏1、6、7的效果优于护理膏8,说明抗菌肽6K-F17与重组乳铁蛋白、重组人源I型胶原α1链蛋白的比例在特定范围时可以更好地发挥作用。
显然,本发明的上述实施例仅仅是为清楚地说明本发明所作的举例,而并非是对本发明的实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明权利要求的保护范围之内。
Claims (10)
1.一种组合物,其特征在于,所述组合物包含抗菌肽6K-F17、重组乳铁蛋白和重组胶原蛋白;
所述重组乳铁蛋白的氨基酸序列如SEQ ID NO:2所示;
所述重组胶原蛋白为重组人源I型胶原α1链蛋白;可选地,所述重组胶原蛋白的氨基酸序列如SEQ ID NO:3所示。
2.如权利要求1所述的组合物,其特征在于,所述抗菌肽6K-F17与重组乳铁蛋白的重量比为0.3:1至2:1,且所述抗菌肽6K-F17与重组胶原蛋白的重量比为0.15:1至1:1。
3.如权利要求1所述的组合物,其特征在于,所述组合物包含按重量计的抗菌肽6K-F170.3份至2份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
4.一种口腔护理产品,其特征在于,所述口腔护理产品包含如权利要求1-3任一项所述的组合物。
5.如权利要求4所述的口腔护理产品,其特征在于,所述口腔护理产品任选自口腔护理膏、口腔用凝胶、口腔喷雾剂、漱口液和口腔冲洗剂。
6.如权利要求4所述的口腔护理产品,其特征在于,所述口腔护理产品还包含选自以下的任一种或更多种:
摩擦剂、保湿剂、溶剂、增稠剂、香料、赋形剂、甜味剂、pH调节剂、表面活性剂、防腐剂、乳化剂、发泡剂、增溶剂、着色剂、抗氧化剂、螯合剂、抗菌剂和抗炎症剂。
7.如权利要求4所述的口腔护理产品,其特征在于,所述口腔护理产品由以下组成:
2%重量份的抗菌肽6K-F17-重组乳铁蛋白-重组胶原蛋白组合物、40%重量份的磷酸氢钙二水合物、6%重量份的丙二醇、1%重量份的十二烷基硫酸钠、0.3%重量份的焦磷酸钠、0.3%重量份的羧甲基纤维素钠、0.3%重量份的黄原胶、15%重量份的山梨醇、0.15%重量份的尼泊金甲酯、0.05%重量份的糖精钠、余量的纯净水;
所述抗菌肽6K-F17-重组乳铁蛋白-重组胶原蛋白组合物包含按重量计的抗菌肽6K-F170.3份至2份、重组乳铁蛋白1份,以及重组胶原蛋白2份。
8.一种根据权利要求1至3任一项所述的组合物在抑制牙龈卟啉单胞菌或制备口腔护理产品中的应用。
9.如权利要求8所述的应用,所述口腔护理产品任选自口腔护理膏、口腔用凝胶、口腔喷雾剂、漱口液和口腔冲洗剂。
10.一种根据权利要求4至7任一项所述的口腔护理产品的制备方法,其特征在于,所述制备方法包括以下步骤:
将权利要求1至3任一项所述的组合物与其它原料混合均匀,得到所述口腔护理产品。
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101519449A (zh) * | 2001-08-30 | 2009-09-02 | 比奥雷克西斯药物公司 | 经修饰的运铁蛋白融合蛋白 |
US20150290278A1 (en) * | 2014-04-15 | 2015-10-15 | The Hospital For Sick Children | Cationic antimicrobial peptides |
CN110964099A (zh) * | 2019-02-20 | 2020-04-07 | 江苏悦智生物医药有限公司 | 酵母重组人源I型胶原α1链蛋白、合成方法及其应用 |
US20220031575A1 (en) * | 2019-11-05 | 2022-02-03 | Zhejiang University | Tooth mineralization solution and mineralization method thereof |
CN114437238A (zh) * | 2022-01-26 | 2022-05-06 | 浙江工业大学 | 胶原蛋白肽-牛乳铁蛋白肽融合蛋白、基因及其表达方法 |
CN115232193A (zh) * | 2021-04-23 | 2022-10-25 | 中国科学院理化技术研究所 | 一种抗菌多肽修饰的蛋白衍生物及其制备方法和应用 |
CN115337218A (zh) * | 2022-06-02 | 2022-11-15 | 贝乐科(上海)生物科技有限公司 | 一种口腔护理组合物、其应用以及含有其的牙膏、漱口水、口腔凝胶 |
-
2023
- 2023-09-25 CN CN202311255386.6A patent/CN117064788B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101519449A (zh) * | 2001-08-30 | 2009-09-02 | 比奥雷克西斯药物公司 | 经修饰的运铁蛋白融合蛋白 |
US20150290278A1 (en) * | 2014-04-15 | 2015-10-15 | The Hospital For Sick Children | Cationic antimicrobial peptides |
CN110964099A (zh) * | 2019-02-20 | 2020-04-07 | 江苏悦智生物医药有限公司 | 酵母重组人源I型胶原α1链蛋白、合成方法及其应用 |
US20220031575A1 (en) * | 2019-11-05 | 2022-02-03 | Zhejiang University | Tooth mineralization solution and mineralization method thereof |
CN115232193A (zh) * | 2021-04-23 | 2022-10-25 | 中国科学院理化技术研究所 | 一种抗菌多肽修饰的蛋白衍生物及其制备方法和应用 |
CN114437238A (zh) * | 2022-01-26 | 2022-05-06 | 浙江工业大学 | 胶原蛋白肽-牛乳铁蛋白肽融合蛋白、基因及其表达方法 |
CN115337218A (zh) * | 2022-06-02 | 2022-11-15 | 贝乐科(上海)生物科技有限公司 | 一种口腔护理组合物、其应用以及含有其的牙膏、漱口水、口腔凝胶 |
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