CN116808043A - 依克多因或其衍生物在预防和/或减轻口腔炎症中的用途及实现该用途的方法 - Google Patents
依克多因或其衍生物在预防和/或减轻口腔炎症中的用途及实现该用途的方法 Download PDFInfo
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- CN116808043A CN116808043A CN202310735807.9A CN202310735807A CN116808043A CN 116808043 A CN116808043 A CN 116808043A CN 202310735807 A CN202310735807 A CN 202310735807A CN 116808043 A CN116808043 A CN 116808043A
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
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- Communicable Diseases (AREA)
- Oncology (AREA)
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- Oral & Maxillofacial Surgery (AREA)
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Abstract
本申请公开了依克多因或其衍生物用于预防和/或减轻口腔炎症的用途以及实现该用途的方法。依克多因或其衍生物能够降低牙龈卟啉单胞菌脂多糖引起的口腔炎症,这为新型口腔护理产品的开发制备提供理论基础和依据。
Description
技术领域
本申请涉及口腔护理技术领域,尤其涉及依克多因或其衍生物在预防和/或减轻口腔炎症中的用途及实现该用途的方法。
背景技术
口腔致病菌脂多糖(LPS)诱导的口腔炎症与一些皮肤炎症的致病机理和对应的处理方式均存在较大差异。在致病性上,由于口腔粘膜与皮肤相比,存在缺少颗粒层和角质层、细胞角化不全、细胞间连接不紧密等组织学上的差异,导致口腔微生物极易损伤口腔组织甚至进入人体体液体统,诱发诸多口腔问题。而皮肤炎症可以由多种因素引起,例如过敏、遗传因素、UV、刺激性化学物质等。在处理方式上,通过抑制由口腔致病菌产生的脂多糖诱导的炎症可以有效减轻口腔炎症。而皮肤炎症与口腔致病菌产生的脂多糖无关,通过以上对口腔炎症的处理方式并不会必然减轻皮肤炎症,反之亦然。因此,口腔炎症与皮肤炎症是完全不同的炎症。
并且引起炎症的不同菌种所产生的LPS之间也存在较大的差异,例如,牙龈卟啉单胞菌LPS与大肠杆菌LPS在结构和各种生物学功能上都有所不同(Bainbridge et al.,2002;Zhang et al.,2008);又如,牙龈卟啉单胞菌LPS可以同时通过TLR2和TLR4诱导的LBP表达,而大肠杆菌LPS只能通过TLR4诱导LBP表达(Ding et al.,2012);这些差异的存在使得两种LPS对人牙髓细胞引起的炎症反应也截然不同(Mojtahedi et al.,2022),并最终导致其引发宿主反应的差异性。已有多项研究证实,牙龈卟啉单胞菌产生的脂多糖(Pg.LPS)是细菌外膜的主要致病成分。Pg.LPS可直接作用于牙周组织细胞,刺激单核细胞和巨噬细胞等效应细胞,诱发炎症反应进而引起牙周组织的破坏。因此,减轻Pg.LPS诱导产生的炎症至关重要。可见,减轻或抑制大肠杆菌LPS引起的炎症并不必然能减轻或抑制牙龈卟啉单胞菌LPS引起的炎症,反之亦然。
发明内容
本申请通过研究发现,依克多因或其衍生物能够预防和/或减轻口腔炎症,特别是由牙龈卟啉单胞菌脂多糖引起的口腔炎症,从而完成了本申请。
本申请具体的技术方案如下:
1.依克多因或其衍生物用于预防和/或减轻口腔炎症的用途。
2.根据项1所述的用途,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的口腔炎症。
3.根据项1或2所述的用途,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的牙龈炎。
4.根据项1-3中任一项所述的用途,所述依克多因衍生物包括羟基依克多因、依克多因钠盐或依克多因钾盐。
5.一种预防和/或减轻口腔炎症的方法,所述方法包括在口腔中施用依克多因和/或其衍生物。
6.根据权利要求5所述的方法,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的口腔炎症。
7.根据权利要求5或6所述的方法,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的牙龈炎。
8.根据权利要求5-7任一项所述的方法,所述依克多因衍生物包括羟基依克多因、依克多因钠盐或依克多因钾盐。
发明效果
依克多因或其衍生物能够预防和/或减轻口腔炎症,特别是由牙龈卟啉单胞菌脂多糖引起的口腔炎症,这为新型口腔护理产品的开发制备提供理论基础和依据。
附图说明
附图用于更好地理解本申请,不构成对本申请的不当限定。其中:
图1为各组中炎症因子IL-6的浓度。
具体实施方式
以下对本申请的示范性实施例做出说明,其中包括本申请实施例的各种细节以助于理解,应当将它们认为仅仅是示范性的。因此,本领域普通技术人员应当认识到,可以对这里描述的实施例做出各种改变和修改,而不会背离本申请的范围和精神。同样,为了清楚和简明,以下的描述中省略了对公知功能和结构的描述。
本申请提供了一种提供了依克多因或其衍生物新的用途,以及实现该用途的方法。
一方面,本申请提供了依克多因或其衍生物用于预防和/或减轻口腔炎症的用途。
所述依克多因指Ectoine,化学名为2-甲基-1,4,5,6,-四氢嘧啶-4-羧酸,是一种存在于微生物中的氨基酸衍生物,属于环状氨基酸。近年来许多研究表明,依克多因具有延缓皮肤衰老、防紫外线、抗氧化、保湿等功效,同时可应用于镇静和舒缓受刺激,并显著增加皮肤的再生过程。基于上述功效,依克多因常用于具有保湿、抗衰等作用的护肤品中。
本申请通过研究发现,依克多因或其衍生物能够有效预防和/或减轻口腔炎症,从而可以将其应用于个人护理品中,用于预防和/或减轻口腔炎症,所述个人护理品可以是口服制剂,也可以是外用制剂。
本申请还提供了依克多因或其衍生物在制备预防和/或减轻口腔炎症的个人护理品中的用途。进一步地,本申请提供了依克多因或其衍生物作为唯一活性成分在制备预防和/或减轻口腔炎症的个人护理品中的用途。对于具体的制剂类型,本申请不做限制,本领域技术人员可以根据使用需要自行在现有技术中进行选择,例如,所述口服制剂可以是粉剂、颗粒剂、胶囊、液体制剂、混悬液等,所述外用制剂可以是敷贴、喷剂、膏霜、液体涂抹制剂等。一种具体的实施方式中,所述个人护理品为外用制剂。
在一些实施方式中,所述个人护理品包括漱口水、牙膏、散剂、含片或口腔贴膜。对于漱口水、牙膏、散剂、含片或口腔贴膜的制备方法,本申请不作任何限制,其均可以通过本领域常规的制备方法制备得到。
在一些实施方式中,所述个人护理品还包括抗菌剂、抗龋剂、抗敏剂、抗结石剂、抗炎剂、美白剂、保湿剂中的一种或两种以上。
例如,所述依克多因或其衍生物可以与包括抗菌剂、抗龋剂、抗敏剂、抗结石剂、抗炎剂、美白剂、保湿剂中的任一种或者任两种或者任三种或者任四种或者与上述所述的全部成分同时用于上述个人护理品中。
在本申请中,对于抗菌剂,本申请不作任何限制,其可以是本领域常规的抗菌剂,例如,所述抗菌剂可以为氯化亚锡、四氢姜黄素、三氯生等。
在本申请中,对于抗龋剂,本申请不作任何限制,其可以是本领域常用的抗龋剂,例如,所述抗龋剂可以为磷酸钙、三偏磷酸钠、甘油磷酸镁、乳磷酸钙等。
在本申请中,对于抗敏剂,本申请不作任何限制,其可以是本领域常用的抗敏剂,例如,所述抗敏剂可以为甘草酸二钾、氟化钾、氯化钾等。
在本申请中,对于抗结石剂,本申请不作任何限制,其可以是本领域常用的抗结石剂,例如,所述抗结石剂可以为焦磷酸盐、三聚磷酸盐、柠檬酸盐等。
在本申请中,对于抗炎剂,本申请不作任何限制,其可以是本领域常用的抗炎剂,例如,所述抗炎剂可以为甲硝唑、替硝唑、奥硝唑等。
在本申请中,对于美白剂,本申请不作任何限制,其可以是本领域常用的美白剂,例如,所述美白剂可以为过氧化物漂白剂、木瓜蛋白酶、葡萄糖氧化酶等。
在本申请中,对于保湿剂,本申请不作任何限制,其可以是本领域常用的保湿剂,例如,所述保湿剂可以为甘油、丙二醇、山梨醇、木糖醇、玻尿酸等。
在一些实施方式中,所述个人护理品还包括pH调节剂、增稠剂、渗透压调节剂中的一种或两种以上。
所述pH调节剂可以为本领域可用的酸、碱、无机盐等;所述增稠剂可以为羟乙基纤维素、羧甲基纤维素及其盐、黄原胶等;所述渗透压调节剂可以是本领域可用的无机盐等。
所述个人护理品中依克多因或其衍生物的量不受限制,只要能起到预防和/或减轻口腔炎症的作用即可,一种具体的实施方式中,所述个人护理品中依克多因或其衍生物的量为0.001wt%~0.1wt%,例如可以为0.002wt%、0.003wt%、0.004wt%、0.005wt%、0.006wt%、0.007wt%、0.008wt%、0.009wt%、0.01wt%、0.015wt%、0.02wt%、0.025wt%、0.03wt%、0.035wt%、0.04wt%、0.045wt%、0.046wt%、0.047wt%、0.048wt%、0.049wt%、0.05wt%、0.06wt%、0.07wt%、0.08wt%、0.09wt%、0.1wt%,一种优选的实施方式中,依克多因或其衍生物的量为0.001wt%~0.05wt%。
本申请还提供了依克多因或其衍生物用于预防和/或减轻口腔炎症的用途。
进一步的,本申请提供了依克多因或其衍生物用于预防和/或减轻口腔炎症的非治疗目的的用途。
所述非治疗目的即不以疾病的诊断或治疗为目的,可以是以预防为目的、以改善为目的、以缓解为目的、以减轻、减缓为目的等等。进一步的,本申请提供了依克多因或其衍生物作为唯一活性成分用于预防和/或减轻口腔炎症的非治疗目的的用途。
进一步的,本申请提供了预防和/或减轻口腔炎症的非治疗目的的方法,所述方法包括在口腔中施用依克多因或其衍生物。所述施用方式可以是本领域内任何一种施用方式,包括但不限于涂抹、含化、雾化、口服、注射等等。
本申请中的依克多因衍生物不受限制,可以是本领域内任何种类的依克多因的衍生物,只要能够预防和/或减轻口腔炎症,包括但不限于经过化学基团修饰的依克多因或依克多因的盐等,一种具体的实施方式中,所述依克多因的衍生物为羟基依克多因、依克多因钠盐或依克多因钾盐。
一种具体的实施方式中,如上所述任何一种依克多因或其衍生物的用途或实现该用途的方法中,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的口腔炎症。
一种具体的实施方式中,如上所述任何一种依克多因或其衍生物的用途或实现该用途的方法中,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的牙龈炎。
本申请提供的依克多因或其衍生物的新用途以及实现该用途的方法,可以改善口腔健康状况,缓解口腔炎症,特别是由牙龈卟啉单胞菌脂多糖引起的口腔炎症,保护口腔,具有广阔的应用前景。
实施例
本申请对试验中所用到的材料以及试验方法进行一般性和/或具体的描述,所用试剂或仪器未注明生产厂商者,均为可以通过市购获得的常规试剂产品。
实施例1
实验材料:牙龈卟啉单胞菌脂多糖(Pg.LPS)(购自sigma)、依克多因(Ectoine)(来自华熙生物科技股份有限公司)、DMEM培养基。
实验样品溶液:将依克多因和牙龈卟啉单胞菌脂多糖分别用DMEM培养基进行稀释,制成含有0.001wt%Ectoine+1μg/ml Pg.LPS终浓度的实验样品溶液。
将CA9-22细胞置于24孔板中培养,待完全贴壁后加入如上实验样品处理24h,之后收集细胞培养液上清。通过酶联免疫检测法(ELISA)检测其在430nm及570nm处的吸光值,根据吸光值计算炎症因子IL-6的浓度。
实施例2
按照实施例1的方法制备含有0.01wt%Ectoine+1μg/ml Pg.LPS终浓度的实验样品溶液,计算炎症因子IL-6的浓度,其他未提及实验过程均与实施例1相同。
实施例3
按照实施例1的方法制备含有0.05wt%Ectoine+1μg/ml Pg.LPS终浓度的实验样品溶液,计算炎症因子IL-6的浓度,其他未提及实验过程均与实施例1相同。
对比例1
按照实施例1的方法制备含有1μg/ml Pg.LPS终浓度的实验样品溶液,计算炎症因子IL-6的浓度,其他未提及实验过程均与实施例1相同。
空白对照组
以空白DMEM培养基作为样品溶液,其中不含有Ectoine和牙龈卟啉单胞菌脂多糖,计算炎症因子IL-6的浓度,其他未提及实验过程均与实施例1相同。
表1各组样品溶液浓度
组别 | 样品溶液浓度 |
空白对照组 | / |
对比例1 | 1μg/ml Pg.LPS |
实施例1 | 0.001wt%Ectoine+1μg/ml Pg.LPS |
实施例2 | 0.01wt%Ectoine+1μg/ml Pg.LPS |
实施例3 | 0.05wt%Ectoine+1μg/ml Pg.LPS |
具体结果如图1所示,从图中可以看到,对比例1单独用1μg/ml的Pg.LPS处理可以引起CA9-22细胞中IL-6浓度显著上调。而与单独Pg.LPS处理组相比,实施例1、2和3中分别加入0.001wt%、0.01wt%、0.05wt%的Ectoine可以显著降低Pg.LPS引起的IL-6浓度,结果表明Ectoine可以减轻牙龈卟啉单胞菌脂多糖引起的炎症。
统计分析:各组与Pg.LPS单独处理组比较采用t-test统计分析,*为p<0.05被认为有统计学差异。**为p<0.01被认为具有显著统计学差异,***为p<0.001被认为有极显著统计学差异。
尽管以上结合对本申请的实施方案进行了描述,但本申请并不局限于上述的具体实施方案和应用领域,上述的具体实施方案仅仅是示意性的、指导性的,而不是限制性的。本领域的普通技术人员在本说明书的启示下和在不脱离本申请权利要求所保护的范围的情况下,还可以做出很多种的形式,这些均属于本申请保护之列。
Claims (8)
1.依克多因或其衍生物用于预防和/或减轻口腔炎症的用途。
2.根据权利要求1所述的用途,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的口腔炎症。
3.根据权利要求1或2所述的用途,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的牙龈炎。
4.根据权利要求1-3中任一项所述的用途,所述依克多因衍生物包括羟基依克多因、依克多因钠盐或依克多因钾盐。
5.一种预防和/或减轻口腔炎症的方法,所述方法包括在口腔中施用依克多因和/或其衍生物。
6.根据权利要求5所述的方法,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的口腔炎症。
7.根据权利要求5或6所述的方法,所述口腔炎症为由牙龈卟啉单胞菌脂多糖引起的牙龈炎。
8.根据权利要求5-7任一项所述的方法,所述依克多因衍生物包括羟基依克多因、依克多因钠盐或依克多因钾盐。
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