CN111163788A - 用于促进透明质酸生成的组合物 - Google Patents
用于促进透明质酸生成的组合物 Download PDFInfo
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- CN111163788A CN111163788A CN201880044270.9A CN201880044270A CN111163788A CN 111163788 A CN111163788 A CN 111163788A CN 201880044270 A CN201880044270 A CN 201880044270A CN 111163788 A CN111163788 A CN 111163788A
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- hyaluronic acid
- lactobacillus plantarum
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- food
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Abstract
本发明的目的在于提供一种用于促进成纤维细胞增殖的组合物和/或用于促进透明质酸合成酶基因表达的组合物。本发明提供一种含有植物乳杆菌L‑137的用于促进成纤维细胞增殖的组合物和/或用于促进透明质酸合成酶基因表达的组合物。
Description
技术领域
本发明涉及一种用于促进透明质酸生成的组合物,更详细而言,涉及一种含有植物乳杆菌L-137的用于促进透明质酸生成的组合物。
背景技术
对于植物乳杆菌L-137,已知其具有预防感冒等各种功效(专利文献1~6及非专利文献1~10),但对于植物乳杆菌L-137的促进成纤维细胞增殖的作用及促进透明质酸合成酶基因表达的作用却一无所知,甚至未曾被暗示。
现有技术文献
专利文献
专利文献1:日本特开2010-95465号公报
专利文献2:日本特开平10-167972号公报
专利文献3:WO2014/199448号册
专利文献4:WO2008/018143号册
专利文献5:WO2004/084923号册
专利文献6:WO2004/084922号册
非专利文献
非专利文献1:Iwasaki.et al,Oral Health Prev Dent.,2016;14(3):207-14.
非专利文献2:Hatano.et al,Int Immunopharmacol.,2015;Apr;25(2):321-31
非专利文献3:Hirose.et al,J Nutr Sci.,2013Dec 6;2:e39
非专利文献4:Fujiki.et al,Biosci Biotechnol Biochem.,2012;76(5):918-22.
非专利文献5:Arimori.et al,Immunopharmacol Immunotoxicol.2012Dec;34(6):937-43
非专利文献6:Hirose.et al,Microbiol Immunol.2010Mar;54(3):143-51.
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发明内容
本发明要解决的技术问题
本发明的目的在于提供一种用于促进成纤维细胞增殖的组合物和/或用于促进透明质酸合成酶基因表达的组合物。
解决技术问题的技术手段
本申请的发明人发现,含有植物乳杆菌L-137的组合物具有促进成纤维细胞增殖的作用、和/或促进透明质酸合成酶基因表达的作用,并进一步进行了研究,从而完成了本发明。
即,本发明如下所述。
[1]一种用于促进成纤维细胞增殖的组合物,其含有植物乳杆菌L-137。
[2]一种用于促进透明质酸合成酶基因表达的组合物,其含有植物乳杆菌L-137。
[3]根据所述[1]或[2]所述的组合物,其用于促进透明质酸的生成。
[4]根据所述[1]或[2]所述的组合物,其用于皮肤病或关节炎的预防、改善或治疗。
[5]一种含透明质酸组合物的制备方法,其具有使(1)(a)植物乳杆菌L-137及(b)免疫细胞或免疫细胞产生成分与(2)成纤维细胞接触的工序。
[6]一种含透明质酸组合物,其通过所述[5]的制备方法制备而成。
[7]所述[1]~[4]及[6]中任一项所述的组合物,其为饮食品。
[8]根据所述[7]所述的组合物,其中,饮食品为食品添加物或补剂(supplement)。
[9]一种促进成纤维细胞增殖和/或透明质酸合成酶基因表达的方法,其包括对摄取者给予植物乳杆菌L-137的有效量的工序。
[9-2]根据所述[9]所述的方法,其中,植物乳杆菌L-137促进透明质酸的生成。
[9-3]根据所述[9]或[9-2]所述的方法,其中,植物乳杆菌L-137预防、改善或治疗皮肤病或关节炎。
[9-4]根据所述[9]~[9-3]中任一项所述的方法,其中,植物乳杆菌L-137包含在饮食品中。
[9-5]根据所述[9-4]所述的方法,其中,饮食品为食品添加物或补剂。
[10]一种植物乳杆菌L-137,其用于促进成纤维细胞增殖和/或透明质酸合成酶基因表达。
[10-2]根据所述[10]所述的植物乳杆菌L-137,所述植物乳杆菌L-137促进透明质酸的生成。
[10-3]根据所述[10]或[10-2]所述的植物乳杆菌L-137,所述植物乳杆菌L-137预防、改善或治疗皮肤病或关节炎。
[10-4]根据所述[10]~[10-3]中任一项所述的植物乳杆菌L-137,所述植物乳杆菌L-137包含在饮食品中。
[10-5]根据所述[10-4]所述的植物乳杆菌L-137,其中,饮食品为食品添加物或补剂。
[11]一种植物乳杆菌L-137在用于促进成纤维细胞增殖和/或透明质酸合成酶基因表达的药物的制备中的应用。
[11-2]根据所述[11]所述的应用,其中,植物乳杆菌L-137促进透明质酸的生成。
[11-3]根据所述[11]或[11-2]所述的应用,其中,植物乳杆菌L-137预防、改善或治疗皮肤病或关节炎。
[11-4]根据所述[11]~[11-3]中任一项所述的应用,其中,植物乳杆菌L-137包含在饮食品中。
[11-5]根据所述[11-4]所述的应用,其中,饮食品为食品添加物或补剂。
[12]一种植物乳杆菌L-137在促进成纤维细胞增殖和/或透明质酸合成酶基因表达中的应用。
[12-2]根据所述[12]所述的应用,其中,植物乳杆菌L-137促进透明质酸的生成。
[12-3]根据所述[12]或[12-2]所述的应用,其中,植物乳杆菌L-137预防、改善或治疗皮肤病或关节炎。
[12-4]根据所述[12]~[12-3]中任一项所述的应用,其中,植物乳杆菌L-137包含在饮食品中。
[12-5]根据所述[12-4]所述的应用,其中,饮食品为食品添加物或补剂。
发明效果
优选本发明的组合物能够起到选自下述效果中的一种以上的效果:(1)促进成纤维细胞增殖的效果;(2)促进例如HAS1或HAS2等透明质酸合成酶基因表达的效果;(3)促进透明质酸生成的效果;(4)预防、改善或治疗例如特应性皮炎、银屑病等皮肤病的效果;(5)预防、改善或治疗例如膝盖疼痛、软骨病损、变形性膝关节症、软骨缺损、软骨损伤或半月板损伤等关节炎的效果。
附图说明
图1为表示透明质酸合成酶1(HAS1)的基因表达量的图表(t检验(student’s t-test),*p<0.01vs.比较例1,平均值±标准偏差)。
图2为表示透明质酸合成酶2(HAS2)的基因表达量的图表(t检验,*p<0.01vs.比较例1,平均值±标准偏差)。
图3为表示成纤维细胞增殖活性的图表(t检验,*p<0.01vs.比较例2,平均值±标准偏差)。
图4为表示透明质酸生成量的图表(t检验,*p<0.01vs.比较例2,平均值±标准偏差)。
具体实施方式
本发明提供(1)含有植物乳杆菌L-137的用于促进成纤维细胞增殖的组合物、和/或(2)含有植物乳杆菌L-137的用于促进透明质酸合成酶基因表达的组合物(以下,也称作本发明的组合物)。
本发明的组合物含有植物乳杆菌L-137。植物乳杆菌L-137以保藏编号FERM BP-08607号(转化自1995年11月30日保藏的FERM P-15317号)保藏于独立行政法人制品评价技术基盘机构专利生物保藏中心(地址:邮政编号292-0818千叶县木更津市上总镰足2-5-8120号室)。另外,即使为植物乳杆菌L-137的突变株,具备植物乳杆菌L-137的特征的菌株也属于植物乳杆菌L-137的范畴。
除了植物乳杆菌L-137以外,本发明的组合物也可含有除此以外的成分。即,本发明的组合物可通过对植物乳杆菌L-137及根据需要而所需的其他成分进行混合、搅拌等而制备。
只要不失去本发明的效果,则除植物乳杆菌L-137以外的成分没有特别限定,例如可使用在医药、药学或食品等领域中已知的任意成分。作为除植物乳杆菌L-137以外的成分,具体而言,可列举出免疫细胞、免疫细胞产生成分或公知的添加剂等。通过使本发明的组合物含有免疫细胞和/或免疫细胞产生成分,能够具有更优异的促进成纤维细胞增殖的活性和/或促进透明质酸生成的活性。
在本发明中,作为免疫细胞,可列举出B细胞或T细胞等淋巴细胞或巨噬细胞等。这些细胞可通过公知的方法从哺乳类或鸟类等的血液或脾脏等中得到,此外也可购买市售品而得到。免疫细胞产生成分只要是免疫细胞所产生的成分则没有特别限定,优选在免疫细胞中的产生因植物乳杆菌L-137与免疫细胞的接触而得到了促进的物质。作为免疫细胞所产生的物质(成分),例如可列举出IL-12、IFN-γ、TNF-α等细胞因子或各种生长因子。
只要发挥本发明的效果,则本发明的组合物中的植物乳杆菌L-137的含量没有特别限定,在100质量%的组合物中,例如可以约为0.001质量%~100质量%的范围,也可以为1~50质量%的范围。
只要发挥本发明的效果,则本发明的组合物中的免疫细胞的数量没有特别限定,可以为1~1×107个细胞/mL。
(植物乳杆菌L-137的获取方法)
植物乳杆菌L-137的培养可根据公知方法、自身公知的方法或以这些方法为基准的方法进行。植物乳杆菌L-137例如可通过在天然培养基、合成培养基或半合成培养基等培养基中进行培养而得到。作为培养基,优选使用含有氮源和/或碳源的培养基。作为所述氮源,例如可列举出肉提取物、蛋白胨、麦谷蛋白(gluten)、酪蛋白、酵母抽提物、氨基酸等。作为所述碳源,例如可列举出葡萄糖、木糖、果糖、肌醇、麦芽糖、水饴、曲汁、淀粉、甘蔗渣、麦麸、糖蜜、丙三醇等。这些氮源和/或碳源可使用一种或组合使用两种以上。
除了所述氮源和/或碳源以外,例如可在所述培养基中进一步添加作为无机质的硫酸铵、磷酸钾、氯化镁、食盐、铁、锰、钼或各种维生素类等中的一种或组合添加两种以上。
在本发明的一个方式中,所述植物乳杆菌L-137的培养温度例如通常约为25~40℃左右,优选约为27~35℃左右。
在本发明的一个方式中,所述植物乳杆菌L-137的培养时间约为12~48小时左右,可进行通气振荡。此外,在本发明的一个方式中,植物乳杆菌L-137的培养可通过通气振荡来进行实施。此外,培养基的pH没有特别限定,通常pH约为3~6,优选pH约为4~6。
植物乳杆菌L-137的菌体可以为活菌体,也可以为死菌体,但从稳定性及操作的容易性等角度出发,优选使用死菌体。
可以在培养结束后,采集菌体后制备加热死菌体,或者也可以不将菌体从培养液中暂时分离,而是将培养液中的菌体制成加热死菌体,然后采集该加热死菌体。作为采集菌体的方法,例如有如下方法:在培养液中加入蒸馏水,通过离心分离等手段去除上清,根据需要重复该操作,通过离心分离或过滤等采集菌体。
植物乳杆菌L-137的加热死菌体可通过以下方式得到:对采集的活菌或含有活菌的培养液整体进行加热处理而使其灭活,并使用喷雾干燥、冻结干燥等适当手段进行干燥。加热温度通常约为60~100℃,优选约为70~90℃,作为加热手段,可以为使用加热器的公知手段。在达到所需温度后,加热时间通常约为5~40分钟,优选约为10~30分钟。
通过上述方式得到的所述死菌体可进一步进行研磨、破碎或冻结干燥处理等,从而制成死菌体处理物。在本发明中,所述死菌体处理物也可适宜地用作死菌体。
(使用方法)
本发明的组合物的给予途径没有特别限定,例如可通过口服或非口服中的任意一种途径对哺乳动物等进行给予。口服给予本发明的组合物时,其与生物体内的免疫细胞接触并发挥效果,非口服给予时,其与常驻在皮肤等中的免疫细胞接触并发挥效果。
口服或注射给予时,植物乳杆菌L-137的剂量或摄取量能够依据摄取者的年龄及体重、症状、给予时间、剂型、给予方法、药剂的组合等而确定。例如,以干燥死菌体计,优选设为成人每人(约60kg)每天摄取约0.5~200mg的植物乳杆菌L-137,更优选设为摄取约1~100mg的植物乳杆菌L-137,进一步优选设为摄取约2~50mg的植物乳杆菌L-137。或者,以活菌换算计,优选设为成人每人(约60kg)每天摄取约(5×108)~(2×1011)cfu(Colonyforming unit;菌落形成单位)的植物乳杆菌L-137,更优选设为摄取约(1×109)~(1×1011)cfu的植物乳杆菌L-137。摄取次数可以为每天一次或分为多次进行。
或者进行外用涂布时,可根据适用的皮肤面积而适当地选择植物乳杆菌L-137的涂布量,通常相对于约10cm2的适用部位的面积,该涂布量优选为每天约0.01~2.5mg,更优选为每天约0.02~1mg。可每天一次或分多次给予乃至适用所述的剂量。
口服给予本发明的组合物时,可以为散剂、颗粒剂、丸剂、片剂、胶囊剂等固体制剂,也可以为糖浆剂等液体制剂。制备这些制剂时,可根据其制剂形态使用载体或添加剂。作为载体或添加剂,例如可列举出赋形剂(聚丙烯酸钠、聚丙烯酸钙、羧甲基纤维素、乳糖、糊精、玉米淀粉、结晶纤维素、白糖、氯化钠、葡萄糖、尿素、淀粉、碳酸钙、高岭土、硅酸、磷酸钾等)、润滑剂(硬脂酸镁、蔗糖脂肪酸酯、甘油脂肪酸酯、精制滑石粉、聚乙二醇等)、崩解剂(羧甲基纤维素钙、无水磷酸氢钙、羧甲基纤维素钠、低取代度羟丙基纤维素、干燥淀粉、海藻酸钠、琼脂粉末、碳酸氢钠、碳酸钙等)、粘合剂(羟丙基纤维素、阿拉伯胶溶液、水、乙醇、丙醇、单糖浆、葡萄糖液、淀粉液、明胶溶液、羧甲基纤维素、甲基纤维素、聚乙烯吡咯烷酮等)、助溶剂(阿拉伯胶、聚山梨酯80等)、吸收促进剂(月桂基硫酸钠等)、缓冲剂(磷酸缓冲液、乙酸缓冲液、硼酸缓冲液、碳酸缓冲液、柠檬酸缓冲液、Tris缓冲液等)、防腐剂(对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯、氯丁醇、苄醇、苯扎氯铵、脱氢乙酸钠、乙二胺四乙酸四钠等)、增稠剂(丙二醇、甘油、羟乙基纤维素、羟丙基纤维素、聚乙烯醇、聚乙二醇等)、稳定剂(亚硫酸氢钠、硫代硫酸钠、乙二胺四乙酸四钠、柠檬酸钠、抗坏血酸、二丁基羟基甲苯等)或pH调节剂(盐酸、氢氧化钠、磷酸、乙酸等)。根据需要,可使用包衣剂(白糖、明胶、羟丙基纤维素、羟丙基甲基纤维素苯二甲酸酯等)进行包覆,也可使用两个以上的层进行包覆。
本发明的组合物没有特别限定,例如可以为饮食品、饲料、药物、准药品(quasidrug)或化妆品等,优选为饮食品等。
含有本发明的组合物的饮食品中可添加通常用于饮食品的食品添加剂,例如甜味剂、着色剂、防腐剂、增稠稳定剂、抗氧化剂、显色剂、漂白剂、防霉剂、胶基、苦味剂、酶、光亮剂、酸味剂、调味剂、乳化剂、强化剂、制造用剂、香料、香辛料提取物等。另外,饮食品中包含功能性表示食品、特定保健用食品、健康食品、患者用食品。
适合于本发明的饮食品没有特别限定。具体而言,例如可列举出作为食品添加物或所谓的营养辅助食品(补剂)的片剂、颗粒剂、散剂、健康饮品等。除此之外,例如可列举出茶饮料、清凉饮料、碳酸饮料、营养饮料、果实饮料、乳酸饮料等饮料;荞麦面、乌冬面、中华面、方便面等面类;糖、糖果、口香糖、巧克力、零食点心、饼干、果冻、果酱、奶油、烘制点心、面包等点心及面包类;鱼糕、火腿、香肠等水产〃畜产加工食品;加工乳、发酵乳等乳制品;色拉油、天妇罗油、人造黄油、蛋黄酱、起酥油、打发鲜奶油、酱汁等油脂及油脂加工食品;沙司、调料汁等调味料;咖喱、炖菜、盖饭、粥、菜粥等蒸煮袋食品;冰激凌、冰糕(sherbet)、刨冰等冰制食品等。
作为含有本发明的组合物的饲料,例如可列举出牛、马、猪等家畜用的饲料、鸡等家禽用的饲料、鱼类等的养殖用饲料、狗、猫等宠物用的饲料等。除了在饲料中添加本发明的组合物以外,本发明的饲料可使用通常的饲料的制备方法来进行加工制备。
此外,本发明的组合物也可掺合在药物中使用。药物可通过掺合植物乳杆菌L-137与公知的药物添加剂等而进行制备。
此外,本发明的组合物也可掺合在准药品或化妆品中使用。作为化妆品,例如可列举出沐浴液、洗手液、洁面剂等清洁剂类;或化妆水、乳液、霜等基础化妆品;粉底(foundation)、妆前乳(under make up)、香粉等化妆品等的化妆品剂型等。
将本发明的组合物制备成饮食品、饲料、药物、准药品或化妆品的形态时,可鉴于本发明的组合物的作用,在该饮食品、饲料、药物、准药品或化妆品、其附属说明书或其包装盒等上标记选自下述主旨中的一种以上:(1)促进成纤维细胞增殖的主旨;(2)促进例如HAS1或HAS2等透明质酸合成酶基因表达的主旨;(3)促进透明质酸生成的主旨;(4)具有预防、改善或治疗例如特应性皮炎、银屑病等皮肤病的效果的主旨;(5)具有预防、改善或治疗例如膝盖疼痛、软骨病损、变形性膝关节症、软骨缺损、软骨损伤或半月板损伤等关节炎的效果的主旨。
通过分别促进成纤维细胞的增殖和/或促进透明质酸合成酶基因的表达,能够预防、改善或治疗皮肤病及关节炎。
优选本发明的组合物可起到选自以下效果中的一种以上的效果:(1)促进成纤维细胞增殖的效果;(2)促进例如HAS1或HAS2等透明质酸合成酶基因表达的效果;(3)促进透明质酸生成的效果;(4)预防、改善或治疗例如特应性皮炎、银屑病等皮肤病的效果;(5)预防、改善或治疗例如膝盖疼痛、软骨病损、变形性膝关节症、软骨缺损、软骨损伤或半月板损伤等关节炎的效果。
针对有无促进成纤维细胞增殖的效果,例如在超过未添加试样的对照的成纤维细胞增殖能力时,能够判断为该试样具有促进成纤维细胞增殖的效果。
针对有无促进透明质酸合成酶基因表达的效果,例如在超过未添加试样的对照的透明质酸合成酶基因表达能力时,能够判断为该试样具有促进透明质酸合成酶基因表达的效果。
针对有无促进透明质酸生成的效果,例如在超过未添加试样的对照的透明质酸生成能力时,能够判断为该试样具有促进透明质酸生成的效果。
针对有无皮肤病的改善或治疗效果,例如在试样给予前与给予后,在问卷调查结果的检查项目“痒”等中确认到显著差异时,能够判断为该试样具有皮肤病的改善或治疗效果。
针对有无关节炎的改善或治疗效果,例如在试样给予前与给予后,在WOMAC(Western Ontario and McMaster Universities Osteoarthritis Index)评价、SF-36(MOS 36-Item Short-Form Health Survey)、JKOM(Japanese Knee OsteoarthiritisMeasure)评价等中确认到显著差异时,能够判断为该试样具有关节炎的改善或治疗效果。
本发明提供一种含透明质酸组合物的制备方法,其具有使(1)(a)植物乳杆菌L-137及(b)免疫细胞或免疫细胞产生成分与(2)成纤维细胞接触的工序。
成纤维细胞可以为存在于包括人类在内的哺乳类等的体内的成纤维细胞,也可以为存在于体外的成纤维细胞,但优选为存在于体内的成纤维细胞。上述成分(1)与(2)的接触可通过成分(1)的口服摄取或在皮肤上的涂布而产生,也可通过在成分(2)的培养培养基中添加成分(1)而产生。
本发明提供一种通过上述制备方法制备的含透明质酸组合物(以下,也称作本发明的含透明质酸组合物)。
本发明的含透明质酸组合物可含有上述成分(1)、上述成分(2)或在医药、药学或食品等领域中已知的任意成分。
优选本发明的含透明质酸组合物能够起到选自下述效果中的一种以上的效果:预防、改善或治疗例如特应性皮炎、银屑病等皮肤病的效果;预防、改善或治疗例如膝盖疼痛、软骨病损、变形性膝关节症、软骨缺损、软骨损伤或半月板损伤等关节炎的效果。
本发明的含透明质酸组合物可以为饮食品、化妆品或准药品等,优选为饮食品。当本发明的含透明质酸组合物为饮食品时,具体而言,例如可列举出作为食品添加物或所谓的营养辅助食品(补剂)的片剂、颗粒剂、散剂、健康饮品等。
实施例
以下,列举出实施例及试验例来对本发明进行进一步具体的说明,但本发明并不限定于此。
1.促进HAS1及HAS2基因表达的效果的评价
(a)试样的制备(1)
(实施例1)
在含有500ng/ml的植物乳杆菌L-137加热死菌体(HK L-137)的含10质量%FBS(GEHealthcare HyClone制造)的RPMI1640培养基(Life Technologies Japan Ltd.制造)中,将2.5×106个细胞/ml的作为免疫细胞的BALB/c小鼠脾细胞在37℃下培养48小时,回收培养后的培养基,得到脾细胞培养上清。在含有25质量%的该脾细胞培养上清的含2质量%FBS(GE Healthcare HyClone制造)的D-MEM培养基(Sigma-Aldrich Co.LLC制造)中,将小鼠成纤维细胞(BALB/3T3 clone A31)在37℃下培养3小时。
(比较例1)
除了将“含有500ng/ml的HK L-137的含10质量%FBS(GE Healthcare HyClone制造)的RPMI1640培养基(Life Technologies Japan Ltd.制造)”替换为“未添加HK L-137的培养基”以外,通过与上述实施例相同的工序,得到脾细胞培养上清。在含有25质量%的该脾细胞培养上清的含2质量%FBS(GE Healthcare HyClone制造)的D-MEM培养基(Sigma-Aldrich Co.LLC制造)中,将小鼠成纤维细胞(BALB/3T3 clone A31)在37℃下培养3小时。
(阴性对照1)
在含2质量%FBS(GE Healthcare HyClone制造)的D-MEM培养基(Sigma-AldrichCo.LLC制造)中,将小鼠成纤维细胞(BALB/3T3 clone A31)在37℃下培养3小时。
(阳性对照1)
在含有10ng/ml的表皮生长因子(EGF;Epidermal Growth Factor)的含2质量%FBS(GE Healthcare HyClone制造)的D-MEM培养基(Sigma-Aldrich Co.LLC制造)中,将小鼠成纤维细胞(BALB/3T3 clone A31)在37℃下培养3小时。
(b)试验
使用试剂盒(RNeasy Mini Kit,QIAGEN K.K.Japan),提取培养后的细胞中的RNA。通过RT-PCR法,进行总RNA中的HAS1及HAS2基因的mRNA表达量的相对定量。求出HAS1及HAS2的mRNA表达量相对于作为内部标准的GAPDH的mRNA表达量的比例。在测定中使用的引物序列如表1所示。
[表1]
基因 | 方向 | 引物序列 | 序列号 |
HAS1 | 正向 | 5’-CTATGCTACCAAGTATACCTCG-3’ | 1 |
HAS1 | 反向 | 5’-TCTCGGAAGTAAGATTTGGAC-3’ | 2 |
HAS2 | 正向 | 5’-CGGTCGTCTCAAATTCATCTG-3’ | 3 |
HAS2 | 反向 | 5’-ACAATGCATCTTGTTCAGCTC-3’ | 4 |
GAPDH | 正向 | 5’-AATGTGTCCGTCGTGGATCTGA-3’ | 5 |
GAPDH | 反向 | 5’-AGTGTAGCCCAAGATGCCCTTC-3’ | 6 |
(HAS1)
将结果示于图1。将阴性对照1的基因表达量设为100%时,比较例1中的表达量为77%,实施例1中的表达量为193%。与比较例1相比,实施例1中的HAS 1基因表达量为显著高的值。
(HAS2)
将结果示于图2。将阴性对照1的基因表达量设为100%时,比较例1中的表达量为132%,实施例1中的表达量为242%。与比较例1相比,实施例1中的HAS2基因表达量为显著高的值。
2.成纤维细胞活化作用的评价
(a)试样的制备(2)
除了将小鼠成纤维细胞(BALB/3T3 clone A31)的培养时间由“3小时”变更为“72小时”以外,通过与上述试样的制备(1)相同的工序,得到实施例2、比较例2、阴性对照2及阳性对照2。
(b)试验
通过WST-1法测定细胞增殖(代谢)活性。具体而言,以使含500μM WST-1(WakoPure Chemical Industries,Ltd.制造)及20μM 1-Methoxy PMS(Wako Pure ChemicalIndustries,Ltd.制造)的溶液成为5质量%的方式将其添加至(a)的培养液中。测定刚添加后及在37℃下培养2小时后的培养基的450nm处的吸光度,将吸光度的增加量作为细胞增殖活性。
将结果示于图3。将阴性对照的成纤维细胞增殖活性设为100%时,比较例2中为110%,实施例2中为180%。与比较例2相比,实施例2中的成纤维细胞增殖活性为显著高的值。
3.促进透明质酸合成的作用的评价
(a)试样
使用上述实施例2、比较例2、阴性对照2及阳性对照2。
(b)试验
使用ELISA试剂盒(BTP-96200,Biotech Trading Partners),测定回收的培养基中的透明质酸量。
将结果示于图4。将阴性对照的透明质酸生成量设为100%时,比较例2中的透明质酸生成量为133%,实施例2中的透明质酸生成量为244%。与比较例2相比,实施例2中的透明质酸生成量为显著高的值。
这些结果表示,植物乳杆菌L-137促进单位成纤维细胞的透明质酸合成酶基因表达和/或成纤维细胞增殖,促进透明质酸生成。
工业实用性
本发明的组合物作为以促进透明质酸生成为目的的饮食品、药物、准药品、化妆品、饲料等是有用的。
序列表
<110> 好侍健康食品株式会社
<120> 用于促进透明质酸生成的组合物
<130> KHP192117743.5
<150> JP 2017-168930
<151> 2017-09-01
<160> 6
<170> PatentIn version 3.1
<210> 1
<211> 22
<212> DNA
<213> 引物
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ctatgctacc aagtatacct cg 22
<210> 2
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<212> DNA
<213> 引物
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tctcggaagt aagatttgga c 21
<210> 3
<211> 21
<212> DNA
<213> 引物
<400> 3
cggtcgtctc aaattcatct g 21
<210> 4
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<212> DNA
<213> 引物
<400> 4
acaatgcatc ttgttcagct c 21
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aatgtgtccg tcgtggatct ga 22
<210> 6
<211> 22
<212> DNA
<213> 引物
<400> 6
agtgtagccc aagatgccct tc 22
Claims (12)
1.一种用于促进成纤维细胞增殖的组合物,其含有植物乳杆菌L-137。
2.一种用于促进透明质酸合成酶基因表达的组合物,其含有植物乳杆菌L-137。
3.根据权利要求1或2所述的组合物,其用于促进透明质酸的生成。
4.根据权利要求1或2所述的组合物,其用于皮肤病或关节炎的预防、改善或治疗。
5.一种含透明质酸组合物的制备方法,其具有使(1)(a)植物乳杆菌L-137及(b)免疫细胞或免疫细胞产生成分与(2)成纤维细胞接触的工序。
6.一种含透明质酸组合物,其通过权利要求5所述的制备方法制备而成。
7.根据权利要求1~4及6中任一项所述的组合物,其为饮食品。
8.根据权利要求7所述的组合物,其中,饮食品为食品添加物或补剂。
9.一种促进成纤维细胞增殖和/或透明质酸合成酶基因表达的方法,其包括对摄取者给予植物乳杆菌L-137的有效量的工序。
10.一种植物乳杆菌L-137,其用于促进成纤维细胞增殖和/或透明质酸合成酶基因表达。
11.一种植物乳杆菌L-137在用于促进成纤维细胞增殖和/或透明质酸合成酶基因表达的药物的制备中的应用。
12.一种植物乳杆菌L-137在促进成纤维细胞增殖和/或透明质酸合成酶基因表达中的应用。
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CN117338823A (zh) * | 2023-12-06 | 2024-01-05 | 山东百德生物科技有限公司 | 一种动物酵素发酵液及其制备方法与应用 |
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