CN107073048B - 含有乳酸菌的组合物 - Google Patents
含有乳酸菌的组合物 Download PDFInfo
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- CN107073048B CN107073048B CN201580046006.5A CN201580046006A CN107073048B CN 107073048 B CN107073048 B CN 107073048B CN 201580046006 A CN201580046006 A CN 201580046006A CN 107073048 B CN107073048 B CN 107073048B
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- lactic acid
- bifidobacterium
- lactobacillus
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Abstract
本发明提供一种组合物，其是将乳酸菌或双岐杆菌和具有提高乳酸菌或双岐杆菌的功能的作用的成分混配而成的。本发明涉及一种组合物，其含有选自由叶黄素、鱼油、乳铁蛋白、维生素、γ‑氨基丁酸和锌组成的组中的一种以上的成分、以及乳酸菌或双岐杆菌。
Description
技术领域
本发明涉及含有乳酸菌的组合物。
背景技术
在日本，乳酸菌制剂作为安全性极其优异的肠道调节用药品被长年使用。并且，含有乳酸菌的、用于肠道调节的所谓健康食品也在大量市售。此外，一直以来作为健康食品受到青睐的含有乳酸菌的酸奶、发酵乳获得了调节肠胃状况的特定保健用食品的批准而受到关注。在欧美，含有乳酸菌的食品(益生菌，probiotics)作为不仅具有肠道调节效果而且还发挥出多种作用、对健康维持显示出效果的代表性食品而受到关注，正在大量市售。另外，还在积极地进行以益生菌的产品开发为目的的乳酸菌的研究(非专利文献1)。
已知乳酸菌具有辅助乳糖消化、抵抗肠道致病菌、抑制大肠癌发病、抑制小肠细菌过度增殖、调节免疫功能、抗过敏、降低血脂、降压、抑制尿路感染、抑制幽门螺杆菌感染、抑制肝性脑病等各种各样的功能(非专利文献2)。已表明利用了乳酸菌的牙膏对牙周病也显示出效果(非专利文献3)。由此可见，已阐明乳酸菌不仅改善肠道菌群，而且还改善包括口腔、胃在内的消化道菌群、以及阴道等泌尿生殖系统菌群的平衡，由此带来有益的保健效果。
与乳酸菌同样，双岐杆菌也作为安全性极其优异的肠道调节用药品被长年使用，含有双岐杆菌的、用于肠道调节的所谓健康食品也在大量市售。
另一方面，由于显示屏幕的使用时间的增加、由空调设备导致的空气的干燥、隐形眼镜的使用等，作为近年来具有增加趋势的疾病，可以举出干眼症。干眼症是由于各种原因而伴有泪液功能降低、角膜和结膜上皮损伤的慢性疾病，伴有眼部的不适和视功能异常，在欧美和日本有10％～20％的成人罹患干眼症。以往，为了治疗干眼症，主要采用滴眼给药人工泪液或合成化合物以补充泪液的方法、或使泪液层稳定化的方法。
现有技术文献
非专利文献
非专利文献1：Reuter G.：腸内フローラとプロバイオティクス(肠内菌群和益生菌)(光冈知足编)、17-39页、学会出版中心、1998年
非专利文献2：Sanders ME和Huis in’t Veld J：Antonie van Leeuwenhoek、76卷、293-315页、1999年
非专利文献3：今井龙弥：歯周病が3日でよくなる乳酸菌歯みがき(3天改善牙周病的乳酸菌牙膏)、Makino出版、2000年
发明内容
发明所要解决的课题
如上所述，乳酸菌或双岐杆菌在单独的情况下也具有健康维持功能，但通过与乳酸菌或双岐杆菌同时摄取其它成分，可期待提高乳酸菌或双岐杆菌的功能。但是，迄今为止，对于为了提高乳酸菌或双岐杆菌的效果而将乳酸菌或双岐杆菌与其它成分进行组合的方法尚未进行充分的研究。并且，对于乳酸菌或双岐杆菌的治疗/预防干眼症的效果尚未进行充分的研究。本发明的目的在于提供一种组合物，其含有乳酸菌或双岐杆菌和提高乳酸菌或双岐杆菌的功能的成分。
用于解决课题的手段
本发明人发现，选自由叶黄素、鱼油、乳铁蛋白、维生素、γ-氨基丁酸和锌组成的组中的一种以上的成分可提高乳酸菌或双岐杆菌的功能，从而完成了本发明。
即，本发明涉及一种组合物，其含有选自由叶黄素、鱼油、乳铁蛋白、维生素、γ-氨基丁酸和锌组成的组中的一种以上的成分、以及乳酸菌或双岐杆菌。
上述组合物优选含有叶黄素、鱼油、以及乳酸菌或双岐杆菌。
上述组合物优选进一步含有乳铁蛋白。
上述组合物优选为药物组合物。
上述组合物优选为干眼症治疗用或干眼症预防用的组合物。
另外，本发明涉及一种干眼症治疗用或干眼症预防用的组合物，其含有链球菌(Streptococcus)属、肠球菌(Enterococcus)属、乳杆菌(Lactobacillus)属或双歧杆菌(Bifidobacterium)属的微生物。
发明的效果
本发明的组合物通过含有选自由叶黄素、鱼油、乳铁蛋白、维生素、γ-氨基丁酸和锌组成的组中的一种以上的成分、以及乳酸菌或双岐杆菌，发挥出提高乳酸菌或双岐杆菌的功能的效果。
附图说明
图1是示出试验例1的结果的图。
图2是示出试验例2的结果的图。
图3是示出试验例3的结果的图。
图4是示出试验例4的结果的图。
图5是示出试验例5的结果的图。
图6是示出试验例6的结果的图。
图7是示出试验例7的结果的图。
图8是示出试验例8的结果的图。
图9是示出实施例2的泪液分泌试验(Schirmer’s test)第1法的结果的图。
图10是示出实施例2的BUT检查的结果的图。
图11是示出实施例2的基于荧光素染色的角膜上皮损伤得分的图。
图12是示出实施例2的DEQS的结果的图。
图13是示出实施例3的乳酸菌或双岐杆菌的给药结果的图。
具体实施方式
本发明涉及一种组合物，其含有选自由叶黄素、鱼油、乳铁蛋白、维生素、γ-氨基丁酸和锌组成的组中的一种以上的成分、以及乳酸菌或双岐杆菌。
作为乳酸菌，只要可得到本发明的效果就没有特别限制，可以举出肠球菌(Enterococcus)属、链球菌(Streptococcus)属、乳杆菌(Lactobacillus)属、碱杆菌(Alkalibacterium)属、奇异菌(Atopobacter)属、肉食杆菌(Carnobacterium)属、嗜果糖乳酸细菌(Fructobacillus)属、嗜盐乳杆菌(Halolactibacillus)属、棍状菌(Isobaculum)属、海生乳杆菌(Marinilactibacillus)属、欧鲁森氏菌(Olsenella)属、副乳杆菌(Paralactobacillus)属、矛形细菌(Pilibacter)属、魏斯氏菌(Weissella)属、营养缺陷菌(Abiotrophia)属、巴伐利亚菌(Bavariicoccus)属、颗粒链菌(Granulicatella)属、蜜蜂球菌(Melissococus)属、产乳酸细菌(Lacticigenium)属、乳球菌(Lactococcus)属、明串珠菌(Leuconostoc)属、酒球菌(Oenococcus)属、片球菌(Pediococcus)属、四联球菌(Tetragenococus)属、毛发球菌(Trichooccus)属、漫游球菌(Vagococcus)属等的微生物。
作为肠球菌属的微生物，只要可得到本发明的效果就没有特别限制，具体可以举出屎肠球菌(Enterococcus faecium)、粪肠球菌(Enterococcus faecalis)等，更具体地可以举出屎肠球菌WB2000株(国际保藏编号NITE BP-01913)、屎肠球菌JCM5804株(可由理化学研究所生物资源中心微生物材料开发室获得)。
作为链球菌属的微生物，只要可得到本发明的效果就没有特别限制，具体可以举出粪链球菌(Streptococcus faecalis)(有时称为屎肠球菌)、嗜热链球菌(Streptococcusthermophilus)等。
作为乳杆菌属的微生物，只要可得到本发明的效果就没有特别限制，具体可以举出唾液乳杆菌(Lactobacillus salivarius)、嗜酸乳杆菌(Lactobacillus acidophilus)、干酪乳杆菌(Lactobacillus casei)、格氏乳杆菌(Lactobacillus gasseri)、戊糖乳杆菌(Lactobacillus pentosus)、约氏乳杆菌(Lactobacillus johnsonii)、罗伊乳杆菌(Lactobacillus leuteri)、旧金山乳杆菌(Lactobacillus sanfranciscensis)、卷曲乳杆菌(Lactobacillus crispatus)、Lactobacillus como、鼠李糖乳杆菌(Lactobacillusrhamnosus)等，更具体地可以举出唾液乳杆菌WB21株(国际保藏编号FERM BP-7792)、嗜酸乳杆菌WB2001株(受理编号NITE ABP-02109)、戊糖乳杆菌TJ515株(受理编号FERM ABP-21798)。嗜酸乳杆菌WB2001株(受理编号NITE ABP-02109，国际保藏编号NITE BP-02109)基于布达佩斯条约于2015年8月28日保藏于独立行政法人日本国家技术与评价研究所专利微生物保藏中心(邮编292-0818，千叶县木更津市上总镰足2-5-8 122号室)。戊糖乳杆菌TJ515株(受理编号FERM ABP-21798，国际保藏编号FERM BP-21798)基于布达佩斯条约于2015年8月18日保藏于独立行政法人日本国家技术与评价研究所专利微生物保藏中心(邮编292-0818，千叶县木更津市上总镰足2-5-8 120号室)。
这些之中，优选链球菌属的微生物，更优选粪链球菌，进一步优选为粪链球菌WB2000株。
乳酸菌可以将1种或2种以上的菌种混配使用。关于乳酸菌，可以将按照常规方法在任意的条件下进行培养、通过离心分离等集菌手段从所得到的培养物中分离出的乳酸菌用于本发明。
作为乳酸菌的形态，可以举出乳酸菌、乳酸菌含有物、乳酸菌培养滤液或乳酸菌处理物。
作为乳酸菌，可以举出活菌体、湿菌、干燥菌、死菌体等。作为乳酸菌含有物，可以举出乳酸菌悬浮液、乳酸菌培养物(包括菌体、培养上清液、培养基成分)等。作为乳酸菌培养滤液，可以举出从乳酸菌培养物中除去乳酸菌后的培养滤液。作为乳酸菌处理物，可以举出乳酸菌、乳酸菌含有物、乳酸菌培养滤液的浓缩物、糊化物、干燥物(喷雾干燥物、冷冻干燥物、真空干燥物、转鼓干燥物)、液状物、稀释物等。
乳酸菌的含量可以是任意的，通常为0.0001～90质量％、优选为0.001～20质量％、更优选为0.01～10质量％。另外，关于乳酸菌的含量，本发明的组合物的每一天的摄取量以乳酸菌数计优选为100万～1000亿个、更优选为1000万～1000亿个、进一步优选为1亿～1000亿个。
为了本发明，也可以使用双岐杆菌来代替乳酸菌。
作为双岐杆菌，只要可得到本发明的效果就没有特别限制，具体可以举出双歧杆菌属的微生物。
作为双歧杆菌属的微生物，只要可得到本发明的效果就没有特别限制，具体可以举出两歧双歧杆菌(Bifidobacterium bifidum)、长双歧杆菌(Bifidobacterium longum)、短双岐杆菌(Bifidobacterium breve)、婴儿双岐杆菌(Bifidobacterium infantis)、嗜热双歧杆菌(Bifidobacterium thermophilum)、假长双歧杆菌(Bifidobacteriumpseudolongum)、假小链双歧杆菌(Bifidobacterium pseudocatenulatum)等，更具体地可以举出长双歧杆菌WB1001株(受理编号NITE ABP-02108)。长双歧杆菌WB1001株(受理编号NITE ABP-02108，国际保藏编号NITE BP-02108)基于布达佩斯条约于2015年8月28日保藏于独立行政法人日本国家技术与评价研究所专利微生物保藏中心(邮编292-0818，千叶县木更津市上总镰足2-5-8 122号室)。
双岐杆菌可以将1种或2种以上的菌种混配使用。关于双岐杆菌，可以将按照常规方法在任意的条件下进行培养、通过离心分离等集菌手段从所得到的培养物中分离出的双岐杆菌用于本发明。
作为双岐杆菌的形态，可以举出双岐杆菌、双岐杆菌含有物、双岐杆菌培养滤液或双岐杆菌处理物。
作为双岐杆菌，可以举出活菌体、湿菌、干燥菌、死菌体等。作为双岐杆菌含有物，可以举出双岐杆菌悬浮液、双岐杆菌培养物(包括菌体、培养上清液、培养基成分)等。作为双岐杆菌培养滤液，可以举出从双岐杆菌培养物中除去双岐杆菌后的培养滤液。作为双岐杆菌处理物，可以举出双岐杆菌、双岐杆菌含有物、双岐杆菌培养滤液的浓缩物、糊化物、干燥物(喷雾干燥物、冷冻干燥物、真空干燥物、转鼓干燥物)、液状物、稀释物等。
双岐杆菌的含量可以是任意的，通常为0.0001～90质量％、优选为0.001～20质量％、更优选为0.01～10质量％。另外，关于双岐杆菌的含量，本发明的组合物的每一天的摄取量以双岐杆菌数计优选为100万～1000亿个、更优选为1000万～1000亿个、进一步优选为1亿～1000亿个。
为了提高乳酸菌或双岐杆菌的功能，组合物包含选自由叶黄素、鱼油、乳铁蛋白、维生素、γ-氨基丁酸和锌组成的组中的一种以上的成分、以及乳酸菌或双岐杆菌。组合物优选包含叶黄素、鱼油、以及乳酸菌或双岐杆菌，更优选包含叶黄素、鱼油、乳铁蛋白、以及乳酸菌或双岐杆菌。
叶黄素在组合物中的含量优选为0.0001～90质量％、更优选为0.001～70质量％、进一步优选为0.01～50质量％。作为叶黄素的形态，可以为游离叶黄素、叶黄素酯、叶黄素盐等中的任一种。作为包含叶黄素的成分，可以使用万寿菊提取物等。
鱼油在组合物中的含量优选为0.0001～90质量％、更优选为0.001～80质量％、进一步优选为0.01～70质量％。
乳铁蛋白在组合物中的含量优选为0.0001～90质量％、更优选为0.001～80质量％、进一步优选为0.01～70质量％。
作为维生素，例如可以举出维生素C、维生素E、维生素A、维生素B2等。这些之中，优选维生素C、维生素E。维生素在组合物中的含量优选为0.0001～90质量％、更优选为0.001～70质量％、进一步优选为0.01～50质量％。
γ-氨基丁酸在组合物中的含量优选为0.0001～90质量％、更优选为0.001～70质量％、进一步优选为0.01～50质量％。作为包含γ-氨基丁酸的成分，可以使用米胚芽提取物等。
锌在组合物中的含量优选为0.0001～90质量％、更优选为0.001～70质量％、进一步优选为0.01～50质量％。作为包含锌的成分，可以使用葡萄糖酸锌等。
组合物只要是人或动物能够摄取的组合物就没有特别限定，例如可以制成药物组合物。
作为组合物的给药形态，例如可以举出软胶囊剂、胶囊剂、散剂、细颗粒剂、颗粒剂、片剂、锭剂、糖浆剂、胶冻剂、栓剂、乳膏剂、凝胶、软膏、洗剂、洗涤剂、灌注液、液剂等。通过采用这些给药形态，能够安全地给药或摄取。
组合物可以加入赋形剂、粘结剂、崩解剂、包覆剂、润滑剂、分散剂、稳定剂等通常在药物组合物的制造技术领域中可使用的添加剂，按照常规方法来制造。
作为赋形剂，例如可以举出白糖、乳糖、甘露糖醇、葡萄糖等糖类；玉米淀粉、马铃薯淀粉、大米淀粉、部分α化淀粉等淀粉类等。
作为粘结剂，例如可以举出壳聚糖、糊精、海藻酸钠、卡拉胶、瓜尔胶、阿拉伯树胶、琼脂等多糖类；黄蓍胶、明胶、谷蛋白等天然高分子类；羟丙基纤维素、甲基纤维素、羟丙基甲基纤维素、乙基纤维素、羟丙基乙基纤维素、羧甲基纤维素钠等纤维素衍生物；聚乙烯基吡咯烷酮、聚乙烯醇、聚乙酸乙烯酯、聚乙二醇、聚丙烯酸、聚甲基丙烯酸、乙酸乙烯酯树脂等合成高分子等。
作为崩解剂，例如可以举出羧甲基纤维素、羧甲基纤维素钙、低取代羟丙基纤维素等纤维素衍生物；羧甲基淀粉钠、羟丙基淀粉、玉米淀粉、马铃薯淀粉、大米淀粉、部分α化淀粉等淀粉类等。
作为包覆剂，例如可以举出甲基丙烯酸二甲氨基乙酯-甲基丙烯酸共聚物、聚乙烯醇缩乙醛二乙基氨基乙酸酯、丙烯酸乙酯-甲基丙烯酸共聚物、丙烯酸乙酯-甲基丙烯酸甲酯-甲基丙烯酸三甲基氯化铵乙酯共聚物、乙基纤维素等水不溶性高分子；甲基丙烯酸-丙烯酸乙酯共聚物、羟丙基甲基纤维素邻苯二甲酸酯、醋酸羟丙基甲基纤维素琥珀酸酯等肠溶性高分子；甲基纤维素、羟丙基甲基纤维素、聚乙烯基吡咯烷酮、聚乙二醇等水溶性高分子等。
作为润滑剂，例如可以举出滑石、硬脂酸、硬脂酸钙、硬脂酸镁、胶态二氧化硅、含水二氧化硅、蜡类、氢化油等。
作为分散剂，例如可以举出卵磷脂、甘油脂肪酸酯、聚甘油脂肪酸酯等乳化剂或瓜尔胶等增粘多糖类。
作为稳定剂，例如可以举出蜂蜡、甘油脂肪酸酯、氢化油等。
组合物可以将所需量以一次给药，也可以分成多次给药。
本发明的组合物通过含有选自由叶黄素、鱼油、乳铁蛋白、维生素、γ-氨基丁酸和锌组成的组中的一种以上的成分、以及乳酸菌或双岐杆菌，能够提高乳酸菌或双岐杆菌的功能。作为本发明的组合物的功能，可以举出干眼症治疗作用、干眼症预防作用、眼的感染症预防作用、眼的稳态维持作用、应激减轻作用、抗氧化作用、抗老化作用等。
干眼症是由于泪腺中的泪液分泌量的减少、泪液中的脂质或粘蛋白质异常所致的水分量蒸发促进而使泪液量减少所引起的。由于泪液的减少，会产生角膜表面和结膜表面的慢性刺激或炎症，导致患者生活质量的下降。通过摄取本发明的组合物，能够使因干眼症而下降的泪液分泌量恢复。以往，为了治疗干眼症，主要采用滴眼给药人工泪液或合成化合物以补充泪液或使泪液层稳定化的方法，而本发明的组合物可以通过经口给药进行干眼症的治疗和预防，可以减轻给药时患者的负担。
在将组合物用于干眼症预防用途的情况下，可以通过长时间给药组合物来预防干眼症，但通过一天的给药也可以预防干眼症。
在将组合物用于干眼症治疗用途的情况下，可以通过在干眼症发病后给药1天以上来治疗干眼症。
实施例
在实施例中具体地说明本发明，但本发明不仅限定于这些实施例。
(实施例1)含有乳酸菌的组合物
制造由表1中记载的成分构成的含有乳酸菌的组合物。需要说明的是，各成分可以使用现有公知的成分。
【表1】
使用以下所示的受试动物、应激负荷处置方法、泪液分泌量测定方法、统计分析方法实施了试验例1～8。
(受试动物)
作为受试动物，使用在维持照明12小时、室温23±5℃、相对湿度60±10％的环境的饲养室中驯化了1周的7～8周龄雌性C57BL/6小鼠。
(应激负荷处置方法)
将受试动物每天一次、持续4小时约束在实施了能够呼吸/排泄的处置的聚丙烯制离心管(容量约60mL)内，约束过程中对受试动物的面部进行鼓风(风速0.5～1.0m/S)，由此进行应激负荷处置。应激负荷处置时间以外，在笼内自由摄取饲料(固态饲料、小鼠/大鼠/仓鼠用饲料MF、制造商为东方酵母工业株式会社)和饮水(自来水)。以1组5～6只来实施试验。
(泪液分泌量测定方法)
在应激负荷处置前，将棉线(ZONE-QUICK(注册商标)、昭和药品化工株式会社)分别插入到受试动物的左右外眼角15秒，以0.5mm的精度测定棉线因泪液的渗透而变为褐色的长度。将左右眼的平均值作为个体的泪液分泌量。
(统计分析方法)
数据的统计分析使用统计软件SAS(SAS Institute Inc.制造)和StatLight(Yukms株式会社制造)。实施了以对照组为对照的t检验或Dunnett检验、以及以处置前组为对照的配对t检验。显著水平都是设定为两侧5％，将P值小于0.05视为显著。另外，求出平均值和标准偏差。
[试验例1]预防效果试验1
对于在应激负荷处置前一天和应激负荷处置期间中以10mg/kg或50mg/kg的量、或者在应激负荷处置前5天和应激负荷处置期间中以10mg/kg的量每天一次经口给药实施例1的组合物的受试动物、和作为对照组的未给药实施例1的组合物的受试动物实施3天应激负荷处置。测定各天的受试动物的泪液分泌量，进行了统计分析。
将结果示于图1。未给药实施例1的组合物的受试动物通过应激负荷处置，泪液分泌量大幅下降。通过预给药实施例1的组合物，能够预防泪液分泌量的下降。可知：越是短时间内大量摄取实施例1的组合物(前一天50mg/kg)、或者虽然摄取量少但越是长时间摄取(5天10mg/kg)，越能够抑制泪液分泌量的降低，干眼症预防效果越高。
[试验例2]预防效果试验2
从应激负荷处置5天前起至应激负荷处置开始5天后，对受试动物每天10mg/kg、一天一次经口给药实施例1的组合物。对受试动物实施了7天应激负荷处置。测定各天的受试动物泪液分泌量，进行了统计分析。
将结果示于图2。未给药实施例1的组合物的受试动物通过应激负荷处置，泪液分泌量大幅下降。在给药了实施例1的组合物的受试动物的情况下，虽然给药期间中能够抑制泪液分泌量的降低，但若中止给药则泪液分泌量降低。由该结果可知，通过长时间持续摄取实施例1的组合物，能够实现特别高的干眼症预防效果。
[试验例3]预防效果试验3
从应激负荷处置5天前或14天前起至应激负荷处置结束为止，使受试动物自由摄取以0.06％的浓度混合有实施例1的组合物的饲料。对受试动物实施了5天应激负荷处置。测定各天的泪液分泌量，进行了统计分析。
将结果示于图3。摄取了不含实施例1的组合物的饲料的受试动物通过应激负荷处置，泪液分泌量大幅降低。
在摄取了混合有实施例1的组合物的饲料的受试动物的情况下，可知摄取期间越长，越能够抑制泪液分泌量的降低。由该结果可知，通过将实施例1的组合物作为饮食长时间持续摄取，能够实现特别高的干眼症预防效果。
[试验例4]治疗效果试验1
对于应激负荷处置后确认到泪液分泌量降低的受试动物，以5mg/kg、10mg/kg或50mg/kg的量每天一次经口给药9天实施例1的组合物。对于对照组的受试动物，未给药实施例1的组合物。在实施例1的组合物的给药期间中实施了应激负荷处置。测定各天的受试动物的泪液分泌量，进行了统计分析。
将结果示于图4。在未给药实施例1的组合物的受试动物的情况下，泪液分泌量完全没有恢复。在给药了实施例1的组合物的受试动物的情况下，泪液分泌量与给药量和给药期间相应地得到恢复。由该结果可知，在干眼症发病后，通过摄取实施例1的组合物，能够实现干眼症治疗效果。
[试验例5]治疗效果试验2
对于应激负荷处置后确认到泪液分泌量降低的受试动物，以50mg/kg的量每天一次经口给药9天实施例1的组合物。在给药期间中和给药结束后实施了3天应激负荷处置。测定各天的受试动物的泪液分泌量，进行了统计分析。
将结果示于图5。通过应激负荷处置而降低的受试动物的泪液分泌量在开始实施例1的组合物的经口给药时转向恢复，越是继续实施例1的组合物的经口给药越得到恢复，接近于应激负荷处置前的值。之后，若中止实施例1的组合物的经口给药，则受试动物的泪液分泌量再次降低。由该结果可知，通过持续摄取实施例1的组合物，能够实现特别高的干眼症治疗效果。
(比较例1)
为了明确乳酸菌的干眼症预防效果，作为比较例1，制造了在表1记载的成分中仅不含有乳酸菌的组合物。
[试验例6]预防效果试验4
在应激负荷处置前一天，以50mg/kg的量对受试动物单次经口给药实施例1的组合物或比较例1的组合物。对于对照组的受试动物，未在应激负荷处置前一天给药本发明的组合物。在应激负荷处置前一天、即将进行应激负荷处置前和应激负荷处置后一天，测定了受试动物的泪液分泌量。对泪液分泌量进行了统计分析。
将结果示于图6。未经口给药实施例1的组合物的受试动物通过应激负荷处置，泪液分泌量大幅降低。经口给药了比较例1的组合物的受试动物通过应激负荷处置，泪液分泌量也降低。经口给药了实施例1的组合物的受试动物几乎不存在应激负荷处置导致的泪液分泌量的降低。由该结果可知，在实施例1的组合物中含有乳酸菌对干眼症预防效果很重要。
[试验例7]治疗效果试验3
进行了长期应激负荷试验后的泪液分泌量恢复(治疗)效果试验。对受试动物实施了连续35天应激负荷处置。从应激负荷处置开始后第21天起至第28天为止，对受试动物以10mg/kg/单次经口给药比较例1的组合物。之后，从应激负荷处置开始后第29天起至第36天为止的1周，对受试动物以10mg/kg/单次经口给药实施例1的组合物。测定各天的受试动物的泪液分泌量，进行了统计分析。
将结果示于图7。从应激负荷处置开始后第21天起至第28天为止经口给药了比较例1的组合物的小鼠的泪液分泌量与对照组同样地从应激负荷处置开始后第1天至第36天保持降低的状态。另一方面，对于从应激负荷处置开始后第29天起至第36天为止给药了实施例1的组合物的受试动物来说，在应激负荷处置开始后第1天以后降低的泪液分泌量从开始实施例1的组合物的给药的、应激负荷处置开始后第29天起慢慢恢复，在应激负荷处置开始后第35天恢复至超过应激负荷处置开始前的泪液分泌量的水平。由该结果可知，实施例1的组合物中含有乳酸菌对干眼症治疗效果很重要。
[试验例8]治疗效果试验4
进行了长期应激负荷处置试验后的泪液分泌量恢复(治疗)效果试验。对受试动物实施了连续40天应激负荷处置。从应激负荷处置开始后第13天起至第21天为止，对受试动物以50mg/kg/单次经口给药实施例1的组合物。将应激负荷处置开始后第22天至第28天作为停药期间，之后，从第29天起至第40天为止，对受试动物以10mg/kg/单次经口给药实施例1的组合物。测定各天的受试动物的泪液分泌量，进行了统计分析。
将结果示于图8。未给药实施例1的组合物的受试动物从应激负荷处置开始后第1天起泪液分泌量降低，之后，泪液分泌量完全没有恢复。另一方面，在以50mg/kg/单次经口给药了实施例1的组合物的小鼠的情况下，应激负荷处置开始后第1天以后降低的泪液分泌量在应激负荷处置开始后第14天至第21天泪液分泌量慢慢恢复。停药期间中的应激负荷处置开始后第22天至第28天泪液分泌量显示出降低倾向，但以10mg/kg/单次经口给药实施例1的组合物的第29天至第40天泪液分泌量慢慢恢复。
(实施例2)含有乳酸菌的组合物对人的效果
(含有乳酸菌的组合物及其给药方法)
使存在干眼症自觉症状的20名22岁至59岁的男女每天一次、每次两粒在晚饭后摄取含有表2记载的成分的软胶囊8周。
【表2】
(检查方法)
在软胶囊的摄取前、摄取后进行共计2次的干眼症检查。对全部的眼实施3个项目(泪液分泌试验第1法、BUT检查、基于荧光素染色的角膜结膜上皮损伤得分)的眼症状检查，进而进行2种自觉症状的问卷调查(干眼症QOL问诊表(DEQS)、11个项目的关于眼的自觉症状的VAS评价)。泪液分泌试验第1法、BUT检查、基于荧光素染色的角膜结膜上皮损伤得分按照2006年干眼症诊断基准来实施检查。DEQS使用了干眼症研究会开发的问诊表。
(结果、考察)
除了存在因疼痛等而未接受检查的项目的两人以外，将18人的结果示于图9～12和表3中。在软胶囊摄取后，眼症状的检查结果在全部项目中得到了改善。另外，在自觉症状问卷调查中，软胶囊摄取后得分也得到了改善。由此暗示，本发明的组合物对干眼症症状的改善显示出效果。
【表3】
(实施例3)乳酸菌和双岐杆菌的干眼症治疗或预防效果
(受试动物)
作为受试动物，使用在维持照明12小时、室温23±5℃、相对湿度60±10％的环境的饲养室中驯化了1周的7～8周龄雌性C57BL/6小鼠。
(应激负荷处置方法)
将受试动物每天一次、持续4小时约束在实施了能够呼吸/排泄的处置的聚丙烯制离心管(容量约60mL)内，约束过程中对受试动物的面部进行鼓风(风速0.5～1.0m/S)，由此进行应激负荷处置。应激负荷处置时间以外，在笼内自由摄取饲料(固态饲料、小鼠/大鼠/仓鼠用饲料MF、制造商为东方酵母工业株式会社)和饮水(自来水)。以1组5～6只来实施试验。
(泪液分泌量测定方法)
在应激负荷处置前，将棉线(ZONE-QUICK(注册商标)、昭和药品化工株式会社制造)分别插入到受试动物的左右外眼角15秒，以0.5mm的精度测定棉线因泪液的渗透而变为褐色的长度。将左右眼的平均值作为个体的泪液分泌量。
(乳酸菌和双岐杆菌)
将粪链球菌WB2000株(细菌学上为屎肠球菌WB2000株)、屎肠球菌JCM5804株、唾液乳杆菌WB21株、嗜酸乳杆菌WB2001株、戊糖乳杆菌TJ515株或长双歧杆菌WB1001株的冷冻干燥粉末分别以包含0.34mg的方式悬浮于蒸馏水0.5mL中。对于在应激负荷处置前一天和应激负荷处置期间中按照以冷冻干燥末菌计为17mg/kg的量每天一次经口给药了上述悬浮液的受试动物、以及作为对照组的未给药上述乳酸菌和双岐杆菌的受试动物实施了4天应激负荷处置。测定了应激负荷处置前一天、应激负荷处置第2天和应激负荷处置第4天的受试动物的泪液分泌量。
(结果、考察)
将结果示于图13。对照组的受试动物通过应激负荷处置，泪液分泌量大幅降低。通过预给药上述乳酸菌或双岐杆菌，能够抑制泪液分泌量的降低，显示出干眼症预防效果。特别是粪链球菌WB2000株，与其它菌相比尤其能够抑制泪液分泌量的降低，因而可知可得到较高的干眼症预防效果。
Claims (4)
1.一种经口组合物，其含有叶黄素、鱼油、乳铁蛋白、维生素、γ-氨基丁酸和锌、以及乳酸菌或双岐杆菌，
乳酸菌为屎肠球菌(Enterococcus faecium)WB2000株，屎肠球菌(Enterococcusfaecium)JCM5804株或戊糖乳杆菌(Lactobacillus pentosus)TJ515株，
双岐杆菌为长双歧杆菌(Bifidobacterium longum)WB1001株。
2.如权利要求1所述的经口组合物，其为药物组合物。
3.如权利要求1所述的经口组合物，其用于干眼症治疗或干眼症预防。
4.屎肠球菌(Enterococcus faecium)WB2000株、屎肠球菌(Enterococcus faecium)JCM5804株、戊糖乳杆菌(Lactobacillus pentosus)TJ515株或长双歧杆菌(Bifidobacterium longum)WB1001株在制造干眼症治疗用或干眼症预防用的经口组合物中的应用。
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| WO2017049162A1 (en) | 2015-09-18 | 2017-03-23 | Virun, Inc. | Compositions for providing agents that degrade in water |
| WO2018174938A1 (en) * | 2017-03-23 | 2018-09-27 | Virun, Inc. | Stable dry powders and emulsions containing probiotics and mucoadhesive protein |
| JP7150282B2 (ja) * | 2017-09-14 | 2022-10-11 | 協同乳業株式会社 | 涙液分泌能・涙液安定性を改善するための飲食品または製剤 |
| KR102513994B1 (ko) * | 2022-10-26 | 2023-03-24 | 김태윤 | 반려동물의 눈물 착색예방용 조성물 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004006801A2 (en) * | 2002-07-17 | 2004-01-22 | Biosyntrx, Inc. | Treatment for dry eye syndrome |
| WO2006078811A2 (en) * | 2005-01-21 | 2006-07-27 | Pharmanova Inc. | Pharmaceutical formulations and methods of use |
| CN101803633A (zh) * | 2010-04-23 | 2010-08-18 | 杭州宏胜饮料集团有限公司 | 缓解视疲劳保健乳饮料及其制备方法 |
| CN103687604A (zh) * | 2011-03-01 | 2014-03-26 | 群体创新有限责任公司 | 用于治疗与致病生物膜相关之病症的材料和方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP980342A2 (en) * | 1997-06-25 | 1999-02-28 | Warner Lambert Co | Anti-inflammatory method |
| EP1718602A4 (en) * | 2004-01-30 | 2007-12-12 | Peplin Biolipids Pty Ltd | THERAPEUTIC AND CARRIER MOLECULES |
| FR2889057B1 (fr) * | 2005-08-01 | 2008-07-18 | Oreal | Composition cosmetique et/ou dermatologique pour la prevention et/ou le traitement des peaux sensibles ou seches |
| JP2007204406A (ja) * | 2006-01-31 | 2007-08-16 | Japan Tobacco Inc | 体温制御剤 |
| JP5110314B2 (ja) * | 2006-04-28 | 2012-12-26 | ライオン株式会社 | 睡眠改善用組成物及び睡眠改善剤 |
| SG182959A1 (en) * | 2007-03-30 | 2012-08-30 | Suntory Holdings Ltd | Medicinal composition, food or drink having effect of enhancing parasympathetic nervous activity |
| WO2009051670A2 (en) * | 2007-10-12 | 2009-04-23 | Resolvyx Pharmaceuticals, Inc. | Oxylipin compounds for the treatment of ophthalmic conditions |
| CN101939411A (zh) * | 2008-02-06 | 2011-01-05 | 宝洁公司 | 用于提高呼吸病症免疫应答的组合物、方法和试剂盒 |
| AU2009293475A1 (en) * | 2008-09-19 | 2010-03-25 | Nestec S.A. | Nutritional support to prevent or moderate bone marrow paralysis or neutropenia during anti-cancer treatment |
| RU2013139217A (ru) * | 2011-01-24 | 2015-03-10 | Басф Се | Композиции для улучшения гигиены полости рта |
| US20140065116A1 (en) * | 2011-03-17 | 2014-03-06 | Giovanni Mogna | Probiotic bacteria having antioxidant activity and use thereof |
| CN103637180A (zh) * | 2013-11-01 | 2014-03-19 | 胡安然 | 一种眼睛疾病患者食用的特殊膳食 |
| TWI519644B (zh) * | 2014-04-11 | 2016-02-01 | 大江生醫股份有限公司 | 生產玻尿酸之益生菌株及其用途 |
-
2015
- 2015-08-31 WO PCT/JP2015/074613 patent/WO2016032000A1/ja active Application Filing
- 2015-08-31 US US15/506,940 patent/US20170273326A1/en not_active Abandoned
- 2015-08-31 TW TW104128597A patent/TW201613625A/zh unknown
- 2015-08-31 SG SG11201701577WA patent/SG11201701577WA/en unknown
- 2015-08-31 JP JP2016545660A patent/JP6665099B2/ja active Active
- 2015-08-31 KR KR1020177006661A patent/KR20170045247A/ko unknown
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- 2017-02-28 PH PH12017500357A patent/PH12017500357A1/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004006801A2 (en) * | 2002-07-17 | 2004-01-22 | Biosyntrx, Inc. | Treatment for dry eye syndrome |
| WO2006078811A2 (en) * | 2005-01-21 | 2006-07-27 | Pharmanova Inc. | Pharmaceutical formulations and methods of use |
| CN101803633A (zh) * | 2010-04-23 | 2010-08-18 | 杭州宏胜饮料集团有限公司 | 缓解视疲劳保健乳饮料及其制备方法 |
| CN103687604A (zh) * | 2011-03-01 | 2014-03-26 | 群体创新有限责任公司 | 用于治疗与致病生物膜相关之病症的材料和方法 |
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| JP6665099B2 (ja) | 2020-03-13 |
| US20170273326A1 (en) | 2017-09-28 |
| KR20170045247A (ko) | 2017-04-26 |
| TW201613625A (en) | 2016-04-16 |
| WO2016032000A1 (ja) | 2016-03-03 |
| CN107073048A (zh) | 2017-08-18 |
| JPWO2016032000A1 (ja) | 2017-07-13 |
| PH12017500357A1 (en) | 2017-07-17 |
| SG11201701577WA (en) | 2017-04-27 |
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