CN102088981B - 帮助唾液分泌的唾液酸 - Google Patents
帮助唾液分泌的唾液酸 Download PDFInfo
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- CN102088981B CN102088981B CN2009801262812A CN200980126281A CN102088981B CN 102088981 B CN102088981 B CN 102088981B CN 2009801262812 A CN2009801262812 A CN 2009801262812A CN 200980126281 A CN200980126281 A CN 200980126281A CN 102088981 B CN102088981 B CN 102088981B
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- neuraminate
- acetyl
- salivation
- threonine
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Abstract
本发明大体上涉及唾液分泌受损相关疾病的领域和可用于治疗或预防这些疾病的组合物。本发明的一个实施方案涉及含有唾液酸的组合物,用于治疗和/或预防唾液分泌受损相关疾病。
Description
本发明大体上涉及唾液分泌受损相关疾病的领域和可用于治疗或预防这些疾病的组合物。本发明的一个实施方案涉及含有唾液酸的组合物,用于治疗和/或预防唾液分泌受损相关的疾病。
很多人在良好的健康状态下活到老年。但是在衰老过程中身体发生很多功能和结构变化,并非所有人可轻松应对这些变化。个体间差异的原因是多方面的,包括基因型、营养和行为。
衰老与神经元的功能性变化以及中枢和周围神经***的进行性神经元损失相关。
经常伴随衰老的典型病症是与唾液分泌不足相关的口干感。
这样的口干感可能与吞咽困难相关,这将进一步降低人食用足够量的维持良好健康的普通食物产品的意愿。
因此在本领域需要可用于治疗或预防唾液分泌受损相关问题的组合物。
本发明者已论述了此需要。
因此,本发明的目的是为本领域提供以下组合物,所述组合物可应用于所有人,可施用而不具有害副作用,不昂贵,可用于改善唾液分泌,特别是在老年人中。
此目的通过独立权利要求的主题达到。从属权利要求进一步发展本发明。
唾液酸(SiAc)是神经氨酸(NeuAc)衍生的带电荷的9碳单糖家族。NeuAc是通常在人中形成的唯一唾液酸。在其他脊椎动物也存在例如N-乙醇酰神经氨酸(N-glycolylneuraminic acid,NeuGc)。
目前,唾液酸经常用于婴儿营养领域。例如,Wang概述了SiAc可能涉及婴儿的认知发育(Wang,B.和Brand-Miller,J.(2003)Eur.J.Clin.Nutr.Nov;57(11):1351-69)。简言之,比较母乳喂养和配方奶喂养婴儿的研究证明,与普通婴儿配方奶相比母乳中较高的NeuAc含量与婴儿唾液和大脑中增加的NeuAc有相关性。然而,无法观察到在人中补充NeuAc的行为效应。尽管如此,人们猜测在牛奶中补充NeuAc可以为牛奶提供人奶品质,这可能对儿童的大脑发育有影响。
富含SiAc例如NeuAc的天然来源为,例如,人奶、象奶、印度水牛奶、肉、蛋和鱼。
本发明者将唾液酸施用于老年大鼠。与年轻动物相比,老年动物显示了较少的唾液分泌。令人吃惊的,喂食唾液酸导致了与在年轻动物中发现的唾液分泌相当的、提高的受刺激唾液分泌。
因此,本发明的一个实施方案为包含唾液酸的组合物,用于治疗和/或预防唾液分泌受损的相关疾病。
唾液分泌受损相关疾病可选自吞咽困难、口腔干燥和其组合。
吞咽困难是一种吞咽疾病,其特征在于吞咽的口腔准备困难,或物质从口到胃的移动困难。这还包括食物在口中的定位问题。吞咽困难的原因是神经或肌肉控制的问题。例如,在中风和头/颈的癌症治疗之后颇为常见。吞咽困难危害营养和水化(hydration),可能导致吸入性肺炎和脱水。
口腔干燥是由于降低的唾液分泌功能导致的口干感的医学术语。慢性口干可为不适的,并可导致严重的健康问题。口干可导致尝味困难、咀嚼困难、吞咽困难和说话困难。如果不予治疗,严重的口干可导致蛀牙加剧和口腔感染例如念珠菌感染。
唾液酸的优选形式是N-乙酰神经氨酸。
N-乙酰神经氨酸具有以下同义词和缩写:o-唾液酸;5-Acetamido-3,5-dideoxy-D-glycero-D-galacto-2-nonulosonic acid;5-Acetamido-3,5-dideoxy-D-glycero-D-galactonulosonic acid;醋纽拉酸;N-乙酰-神经氨酸(N-acetyl-neuraminate);N-乙酰神经氨酸(N-Acetylneuraminic acid);NANA和Neu5Ac。
如果组分和/或组合物富含唾液酸则是优选的。
本发明的一个实施方案为用于治疗或预防唾液分泌受损相关疾病的组合物,所述组合物包含蛋白质部分,所述蛋白质部分包含结合在富含苏氨酸的肽/蛋白质骨架上的N-乙酰神经氨酸。
富含苏氨酸的意思是苏氨酸含量高于人蛋白质质量的平均苏氨酸丰度。例如,苏氨酸含量与人蛋白质质量的平均苏氨酸丰度的相比提高至少10%。
因此苏氨酸在蛋白质部分的氨基酸中至少占6.3摩尔-%。
例如,苏氨酸可在氨基酸总数中占约8到22%之间的量。
蛋白质部分可进一步包含以质量计约7至25%的N-乙酰神经氨酸。
N-乙酰神经氨酸可以结合多糖的形式提供。例如N-乙酰神经氨酸可以结合糖蛋白和/或蛋白聚糖的形式提供。
根据本发明特别优选的实施方案,蛋白质部分包含N-乙酰神经氨酸(NeuAc),其特征在于富含苏氨酸的肽/蛋白质骨架(在氨基酸总数中约8到22%之间)和7至25%以质量计的NeuAc含量。
N-乙酰神经氨酸可以寡糖组分的形式提供,例如,其包含糖基化的氨基酸和具有通式RnSacm的肽,其中R为氨基酸残基,Sac为选自N-乙酰神经氨酸、N-乙酰半乳糖胺和半乳糖的单糖,n为1和10之间的值,附带条件是如果n的值为1,则R为苏氨酸残基或丝氨酸残基,如果n的值在2和10之间,则肽包含至少1个苏氨酸或丝氨酸残基,m的值在2和4之间则至少15摩尔%的组分为N-乙酰神经氨酸。
优选的n的值在1和3之间,m的值为3或4。
组分包含至少15摩尔%的唾液酸作为连接在苏氨酸或丝氨酸羟基上的糖链部分。唾液酸可组成链的一部分或其本身作为链中的单糖单元的取代基。
优选的,寡糖组分包含以下单糖:-
化合物 | 摩尔% |
N-乙酰半乳糖胺(GalNAc) | 20-25 |
半乳糖(Gal) | 20-25 |
N-乙酰神经氨酸(NeuAc) | 40-17.5 |
寡糖组分可包含20至25摩尔%的丝氨酸和苏氨酸混合物。
寡糖组分可包含以下糖基化氨基酸或肽:-
NeuAc-α-2,3-Gal-β-1,3-(NeuAc-α-2,6-)-GalNAc-Rn
NeuAc-α-2,3-Gal-β-1,3-GalNAc-Rn
Gal-β-1,3-(NeuAc-α-2,6-)-GalNAc-Rn
Gal-β-1,3-GalNAc-Rn
本发明的寡糖组分可通过CGMP水解制备,同时或相继使用外切蛋白酶和内切蛋白酶以得到游离氨基酸和链长在2和10之间的肽的混合物,将水解混合物经纳米过滤以保留分子量在1000和2000道尔顿之间的部分。
CGMP本身是制造奶酪的副产品,其中全脂奶通过凝乳酶处理以析出酪蛋白。在此过程中,CGMP从κ酪蛋白上切除并和乳清蛋白保留在溶液中。此产品被称为甜乳清。可使用任意本领域已知方法将CGMP从乳清蛋白中分离。合适的方法描述于欧洲专利号986312中。
不受理论限制,基于以下原因,发明者认为包含与富含苏氨酸的肽/蛋白质骨架结合的N-乙酰神经氨酸(例如结合多糖的N-乙酰神经氨酸)的蛋白质部分比游离的N-乙酰神经氨酸有优势。游离N-乙酰神经氨酸导致非常快的“急性”摄取,N-乙酰神经氨酸的***增加通过更高的尿***触发循环N-乙酰神经氨酸水平的重建。包含与富含苏氨酸的肽/蛋白质骨架结合的N-乙酰神经氨酸的蛋白质部分能够避免这一现象。例如,结合多糖的N-乙酰神经氨酸可到达所有的肠部分,在包括小肠下部和结肠的整个肠内导致缓慢的“慢性”N-乙酰神经氨酸摄取。
组合物可对老年人施用。
如果个体已经超过其原籍国平均预期寿命的前1/2,优选的,如果个体已经超过其原籍国平均预期寿命的前2/3,更优选的,如果个体已经超过其原籍国平均预期寿命的前3/4,最优选的,如果个体已经超过其原籍国平均预期寿命的前4/5,则认为个体是“老年人”。
组合物可对人或动物施用,特别是宠物、伴侣动物和/或家畜。
本发明的组合物可为营养组合物、营养食品、饮料、食物添加剂或药物。食物添加剂或药物可为例如片剂、胶囊、锭剂或液体形式。食物添加剂或药物优选的以持续释放制剂提供,以得到延长时间的持续SiAc供给。
组合物优选的选自基于奶粉的产品、方便饮料、可立即饮用的制剂、营养粉、营养液、基于奶的产品特别是酸奶或冰激凌、谷物产品、饮料、水、咖啡、热牛奶咖啡、麦芽饮料、巧克力口味饮料、烹饪产品、汤、外用霜、栓剂、片剂、糖浆和经皮给药的制剂。
奶可为任意可从动物或植物来源得到的奶,优选的为牛奶、人奶、绵羊奶、山羊奶、马奶、骆驼奶、米乳(rice milk)或豆奶。
除了奶以外,可使用来源于奶的蛋白质部分或初乳。
组合物可进一步包含保护性水状胶质(例如树胶、蛋白质、变性淀粉)、粘合物、成膜剂、成胶囊剂/材料、囊/外壳材料、基质化合物、涂料、乳化剂、表面活性剂、加溶剂(油、脂肪、蜡、卵磷脂等等)、吸附剂、载体、填料、共化合物(co-compound)、分散剂、湿润剂、加工助剂(溶剂)、流动剂、掩味剂、增重剂、胶凝剂(jellifying agents)、胶凝剂(gel formingagents)、抗氧化剂和抗菌剂。其还可包含传统药物添加剂和佐剂、赋形剂和稀释剂,包括但不局限于水、任意来源的明胶、植物胶、木素磺酸盐、滑石、糖、淀粉、***树胶、植物油、聚亚烷基二醇、调味剂、防腐剂、稳定剂、乳化剂、缓冲液、润滑剂、着色剂、湿润剂、填料,等等。此外,其可包含适于口或肠施用的有机或无机载体材料及维生素、微量矿物质元素和符合政府机关推荐的例如美国推荐的日摄食量(uSRDA)的其他微量营养素。
例如,组合物可包含每日1次或多次剂量在给定范围内的下述微营养素:-300至500mg钙、50至100mg镁、150至250mg磷、5至20mg铁、1至7mg锌、0.1至0.3mg铜、50至200μg碘、5至15μg硒、1000至3000μg β-胡萝卜素、10至80mg维生素C、1至2mg维生素B1、0.5至1.5mg维生素B6、0.5至2mg维生素B2、5至18mg烟酸、0.5至2.0μg维生素B12、100至800μg叶酸、30至70μg生物素、1至5μg维生素D、3至10μg维生素E。
本发明的组合物可包含蛋白质来源、碳水化合物来源和/或脂来源。
可使用任意合适的膳食蛋白质,例如动物性蛋白质(例如奶蛋白、肉蛋白和卵蛋白);植物性蛋白质(例如大豆蛋白、小麦蛋白、大米蛋白和豌豆蛋白);游离氨基酸的混合物;或其组合。奶蛋白例如酪蛋白和乳清和大豆蛋白是特别优选的。当蛋白质部分包含的苏氨酸为蛋白质部分氨基酸总数的约8和22%之间的量时,可以得到本发明目的的非常阳性的结果。
如果组合物包括脂肪来源,则脂肪来源更优选提供配方5%至40%的能量;例如20%至30%的能量。可添加DHA。可使用芥籽(canola)油、玉米油和高油酸向日葵油混合物得到合适的脂肪谱。
碳水化合物来源可更优选的提供组合物的40%至80%能量。可使用任意合适的碳水化合物,例如蔗糖、乳糖、葡萄糖、果糖、固体玉米糖浆、麦芽糊精和其混合物。
根据本发明特别优选的实施方案,蛋白质部分包含N-乙酰神经氨酸(NeuAc),其特征在于富含苏氨酸的肽/蛋白质骨架(在氨基酸总数的8和22%之间)和7至25%以质量计的NeuAc含量。
组合物还可包含益生菌微生物和/或益生素例如寡聚果糖、寡聚半乳糖(galactosyloligosaccharides)、果胶和/或其水解产物。
如果组合物包含益生菌,由于益生菌和益生素的存在产生协同效应,益生素是特别优选的。
“益生菌”是指对宿主健康或身心健康具有益作用的微生物细胞制备物或微生物细胞组分。(Salminen S,Ouwehand A.Benno Y.等人“Probiotics:how should they be defined”Trends Food Sci.Technol.1999:10 107-10)。
根据本发明可使用所有益生菌微生物。优选的,它们可选自双歧杆菌属(Bifidobacterium)、乳杆菌属(Lactobacillus)、链球菌属(Streptococcus)和酵母属(Saccharomyces)或其混合物,特别选自长双歧杆菌(Bifidobacterium longum)、乳双歧杆菌(Bifidobacteriumlactis)、嗜酸乳杆菌(Lactobacillus acidophilus)、鼠李糖乳杆菌(Lactobacillus rhamnosus)、副干酪乳杆菌(Lactobacillus paracasei)、约氏乳杆菌(Lactobacillus johnsonii)、胚芽乳杆菌(Lactobacillusplantarum)、唾液乳杆菌(Lactobacillus salivarius)、屎肠球菌(Enterococcus faecium)、布拉酵母(Saccharomyces boulardii)和罗伊乳杆菌(Lactobacillus reuteri)或其混合物,优选的选自约氏乳杆菌(NCC533;CNCM I-1225)、长双歧杆菌(NCC490;CNCM I-2170)、长双歧杆菌(NCC2705;CNCM I-2618)、乳双歧杆菌(2818;CNCM I-3446)、副干酪乳杆菌(NCC2461;CNCM I-2116)、鼠李糖乳杆菌GG(ATCC53103)、鼠李糖乳杆菌(NCC4007;CGMCC 1.3724)、屎肠球菌SF 68(NCIMB101415),和其混合物。
“益生素”的意思是在肠中促进益生菌生长的食物成分。它们不在消化其的人胃和/或肠上部被分解或在肠胃道被吸收,但被胃肠微生物群和/或益生菌发酵。在例如Glenn R.Gibson和Marcel B.Roberfroid,DietaryModulation of the Human Colonic Microbiota:Introducing the Conceptof Prebiotics,J.Nutr.1995125:1401-1412中定义了益生素。
根据本发明可使用的益生素没有特别限制,包括所有在肠中促进益生菌生长的食物成分。优选的,它们可选自寡糖,任选的包含果糖、半乳糖、甘露糖;膳食纤维,特别是可溶纤维、大豆纤维;菊粉;或其混合物。优选的益生素为寡聚果糖、寡聚半乳糖(galacto-oligosaccharides)、寡聚异麦芽糖、寡聚木糖、大豆寡糖、糖基蔗糖、乳蔗糖、乳果糖、寡聚异麦芽酮糖、寡聚麦芽糖、树胶和/或其水解产物、果胶和/或其水解产物。
发现本发明组合物中唾液酸的效果基本上是剂量依赖性的。小剂量将产生较小的效果,大剂量可能过大以致身体无法利用所有提供的SiAc。需要提供的SiAc的确切量将取决于例如待治疗者及其病症。
尽管一般来说SiAc的每种剂量都会产生有益的效果,发现如果唾液酸以每克组合物干质量1mg-250mg的量存在于组合物中时是特别优选的。
唾液酸可以1mg-2g/kg待治疗者体重的每日量施用,优选的0.025g至0.8g/kg体重。
本领域技术人员应当理解,在不背离公开的发明范围内,他们可以自由组合此处描述的本发明的所有特征。特别的,可将用于描述本发明用途的特征应用于本发明的组合物,反之亦然。
通过以下实施例和图,本发明的其他优势和特征是显而易见的。
图:
图1证明通过测量每次受刺激的唾液产生,与年轻成年大鼠相比,老年大鼠显示了较低的胆碱能神经元活性,但在用富含唾液酸的饮食喂养后显示了显著提高的神经元活性。显示了平均值和平均值的标准误差。N=9-10;*表示用t-检验比较喂养对照饮食的3个月和24个月大鼠,在p=0.0035水平上差异显著,和比较喂养对照和Sia饮食的24个月大鼠,在p=0.0024水平上差异显著。
图2再次显示在喂养对照饮食(空心棒)或富含NeuAc的饮食(实心棒)3周的年轻成年大鼠(3个月)和老年大鼠(24个月)中用匹鲁卡品(Pilocarpine)刺激的唾液分泌。显示了平均值和标准差(SD)。双因素方差分析(2-way ANOVA)显示了显著的年龄(p=0.0364)和治疗效应(p=0.0037),和接近显著的相互作用(p=0.0550)效应。值得注意的是,喂养NeuAc在老年大鼠中提高受刺激的唾液分泌比在年轻成年大鼠中明显更有效。
实施例
用以浓度为0.15g/100g饮食包含唾液酸的半合成饮食(对照)或另外添加唾液酸至终浓度0.9g/100g饮食的半合成饮食(Sia)喂养年轻成年大鼠(3个月)和老年大鼠(24个月)。
喂养试验饮食3周后,评估胆碱能神经元的神经元活性。为此,用匹鲁卡品(IP,1.5mg/kg体重用于24个月大鼠和2mg/kg体重用于3个月大鼠)注射大鼠。匹鲁卡品是作用于胆碱能神经元的蕈毒碱激动剂,其导致唾液分泌。以此方式用精密计时器对受刺激的唾液收集计时。约7分钟后终止收集。
如在图1和2中所看见的,与年轻动物相比,老年动物显示了较少的受刺激唾液分泌。在用唾液酸喂养后,老年动物达到了和年轻动物类似的受刺激唾液分泌。这表示喂养唾液酸帮助随年龄降低的胆碱能神经元功能的功能性恢复。
此处观察到的现象显示,通过营养途径提供唾液酸在老年动物中重建了适当的唾液分泌。
Claims (23)
1.唾液酸的组合物,用于治疗或预防唾液分泌受损的相关疾病,其中所述组合物包含蛋白质部分,其中蛋白质部分包含约7至25%以质量计的N-乙酰神经氨酸和占氨基酸总数约8至22%之间量的苏氨酸,其中N-乙酰神经氨酸与富含苏氨酸的肽/蛋白质骨架结合。
2.根据权利要求1的组合物,其中N-乙酰神经氨酸作为寡糖组分被提供,所述寡糖组分包含糖基化的氨基酸和通式为RnSacm的肽,其中R为氨基酸残基,Sac为选自N-乙酰神经氨酸、N-乙酰半乳糖胺和半乳糖的单糖,n为1至10之间的值,附带条件是如果n的值为1,则R为苏氨酸残基或丝氨酸残基,如果n的值在2和10之间,则肽包含至少1个苏氨酸或丝氨酸残基,m的值在2和4之间且至少15mol%的组分为N-乙酰神经氨酸。
3.根据权利要求1的组合物,其中唾液分泌受损的相关疾病选自吞咽困难、口腔干燥和其组合。
4.根据权利要求1的组合物,其中组合物为药物组合物、食物产品、或食物添加剂。
5.根据权利要求1的组合物,其中组合物为营养食品。
6.根据权利要求1的组合物,其中组合物还包含神经元保护剂;和/或益生菌微生物和/或益生素。
7.权利要求6的组合物,其中所述神经元保护剂为抗氧化植物提取物、维生素或微营养素。
8.权利要求6的组合物,其中所述益生素为寡聚果糖、寡聚半乳糖、果胶和/或其水解产物。
9.根据权利要求1的组合物,其中N-乙酰神经氨酸以每克组合物干质量1mg-250mg的量存在于组合物中。
10.根据权利要求1的组合物,其中N-乙酰神经氨酸以1mg-2g/kg体重的每日量施用给受试者。
11.根据权利要求1的组合物,其中组合物选自酸奶、冰激凌、饼干、谷物棒、水、热牛奶咖啡、茶、果汁、麦芽饮料、巧克力口味饮料、汤、巧克力、外用霜、栓剂、片剂、和糖浆。
12.根据权利要求1的组合物,其中组合物为基于奶粉的产品。
13.根据权利要求1的组合物,其中组合物为方便饮料。
14.根据权利要求1的组合物,其中组合物为可立即饮用的制剂。
15.根据权利要求1的组合物,其中组合物为营养粉。
16.根据权利要求1的组合物,其中组合物为营养液。
17.根据权利要求1的组合物,其中组合物为基于奶的产品。
18.根据权利要求1的组合物,其中组合物为谷物产品。
19.根据权利要求1的组合物,其中组合物为饮料。
20.根据权利要求1的组合物,其中组合物为咖啡。
21.根据权利要求1的组合物,其中组合物为烹饪产品。
22.根据权利要求1的组合物,其中组合物为糖食产品。
23.根据权利要求1的组合物,其中组合物为经皮应用的制剂。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP08155853A EP2116139A1 (en) | 2008-05-08 | 2008-05-08 | Sialic acid to support brain health in the elderly |
EP08155853.8 | 2008-05-08 | ||
PCT/EP2009/055461 WO2009135867A1 (en) | 2008-05-08 | 2009-05-06 | Sialic acid to support salivation |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102088981A CN102088981A (zh) | 2011-06-08 |
CN102088981B true CN102088981B (zh) | 2013-01-02 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN2009801262812A Expired - Fee Related CN102088981B (zh) | 2008-05-08 | 2009-05-06 | 帮助唾液分泌的唾液酸 |
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Country | Link |
---|---|
US (1) | US20110124579A1 (zh) |
EP (2) | EP2116139A1 (zh) |
JP (1) | JP2011519896A (zh) |
CN (1) | CN102088981B (zh) |
AU (1) | AU2009245798A1 (zh) |
BR (1) | BRPI0912227A2 (zh) |
CA (1) | CA2723744A1 (zh) |
MX (1) | MX2010012253A (zh) |
RU (1) | RU2495668C2 (zh) |
WO (1) | WO2009135867A1 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2116140A1 (en) * | 2008-05-08 | 2009-11-11 | Nestec S.A. | Sialic acid to support the immune system in the elderly |
BR112012023004A2 (pt) * | 2010-03-12 | 2015-09-15 | Dsm Ip Assets Bv | suplementação maternal de ácido siálico. |
WO2012117065A1 (en) | 2011-03-01 | 2012-09-07 | Nestec S.A. | Extensional viscosity to promote safe swallowing of food boluses |
WO2014031837A1 (en) * | 2012-08-22 | 2014-02-27 | The Regents Of The University Of California | Compositions and methods for enhancing sialic acid levels in tissue |
US20150305385A1 (en) * | 2014-04-25 | 2015-10-29 | Mead Johnson Nutrition Company | Pediatric nutritional composition with human milk oligosaccahrides, prebiotics and probiotics |
JP6422107B2 (ja) * | 2016-01-26 | 2018-11-14 | 公益財団法人ヒューマンサイエンス振興財団 | 容器詰飲料 |
AU2018327184A1 (en) * | 2017-08-31 | 2020-03-05 | Megmilk Snow Brand Co., Ltd. | Intestinal environment improvement composition and method for manufacturing same |
Citations (1)
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WO2003090703A1 (de) * | 2002-04-25 | 2003-11-06 | Gaba International Ag | Mundpflegemittel enthaltend ovomucin |
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JPH03123445A (ja) * | 1989-10-07 | 1991-05-27 | Taiyo Kagaku Co Ltd | シアル酸徐放性食品 |
JPH07258093A (ja) * | 1994-03-23 | 1995-10-09 | Morinaga Milk Ind Co Ltd | 神経成長因子様剤 |
US5763438A (en) * | 1994-06-10 | 1998-06-09 | Seikagaku Corporation | 2-acylaminopropanol compound and medical composition |
JPH08266255A (ja) * | 1995-03-30 | 1996-10-15 | Taiyo Kagaku Co Ltd | 学習能力向上組成物 |
JP3703199B2 (ja) * | 1996-03-01 | 2005-10-05 | タカラバイオ株式会社 | モノシアロガングリオシドgm1の製造方法 |
JP4044630B2 (ja) * | 1996-05-16 | 2008-02-06 | 雪印乳業株式会社 | 脳機能改善剤 |
JP2997419B2 (ja) * | 1996-05-31 | 2000-01-11 | 雪印乳業株式会社 | 脳ガングリオシド含量減少抑制剤 |
IE970541A1 (en) * | 1997-07-25 | 1999-01-27 | Michael Anthony Folan | Maternal immune secretions and their use in the treatment and/or prophylaxis of the buccal cavity |
US6444649B1 (en) * | 1998-04-10 | 2002-09-03 | Mitsubishi Chemical Corporation | Solid dispersion containing sialic acid derivative |
AUPQ275799A0 (en) * | 1999-09-10 | 1999-10-07 | Luminis Pty Limited | Recombinant bacterium expressing an oligosaccharide receptor mimic |
JP4717175B2 (ja) * | 2000-01-27 | 2011-07-06 | 雪印乳業株式会社 | シアロムチンの分泌促進剤 |
US7112668B2 (en) * | 2001-01-23 | 2006-09-26 | Curagen Corporation | Polypeptides and nucleic acids encoded thereby |
EP1421208A4 (en) * | 2001-04-11 | 2004-10-06 | Bristol Myers Squibb Co | FOR TWO NEW HUMAN G-PROTEIN-COUPLED RECEPTORS, HGPRBMY28 AND HGPRBMY29, CODING POLYNUCLEOTIDES AND SPONGE VARIANTS THEREOF |
US6482396B1 (en) * | 2001-05-15 | 2002-11-19 | Campina Melkunie B.V. | Methods for treating or preventing diseases of the oral cavity |
FR2833268B1 (fr) * | 2001-12-12 | 2005-07-08 | Fabre Pierre Dermo Cosmetique | Nouvelle association contenant un poloxamer et de l'acide chondroitine sulfurique et/ou une glycoproteine et son utilisation |
US7951410B2 (en) * | 2003-04-14 | 2011-05-31 | Mead Johnson Nutrition Company | Enteral compositions containing caseinoglycomacropeptide having an enhanced concentration of sialic acid |
CN1248603C (zh) * | 2003-05-14 | 2006-04-05 | 韩孝大 | 一种抗病毒感染多功能饮料 |
US20050096263A1 (en) * | 2003-10-30 | 2005-05-05 | Keay Susan K. | Novel antiproliferative factor and methods of use |
JP2006265210A (ja) * | 2005-03-25 | 2006-10-05 | Marukin Bio Inc | 血管平滑筋細胞の増殖抑制剤 |
US20060247153A1 (en) * | 2005-04-29 | 2006-11-02 | Mcmahon Robert J | Method of improving learning and memory in mammals |
CN1701789A (zh) * | 2005-05-13 | 2005-11-30 | 韩孝清 | 含有唾液酸及其衍生物的营养补充剂 |
PT1965787E (pt) * | 2005-11-30 | 2013-07-05 | Endo Pharmaceuticals Inc | Tratamento de xerostomia com um antioxidante que contém enxofre |
FR2905268B1 (fr) * | 2006-09-01 | 2009-01-23 | Unither Dev Soc Par Actions Si | Substitut salivaire |
JP4005115B1 (ja) * | 2007-02-08 | 2007-11-07 | 日本臓器製薬株式会社 | 疼痛疾患治療剤 |
-
2008
- 2008-05-08 EP EP08155853A patent/EP2116139A1/en not_active Withdrawn
-
2009
- 2009-05-06 JP JP2011507909A patent/JP2011519896A/ja active Pending
- 2009-05-06 AU AU2009245798A patent/AU2009245798A1/en not_active Abandoned
- 2009-05-06 WO PCT/EP2009/055461 patent/WO2009135867A1/en active Application Filing
- 2009-05-06 EP EP09742085A patent/EP2293799A1/en not_active Withdrawn
- 2009-05-06 MX MX2010012253A patent/MX2010012253A/es unknown
- 2009-05-06 BR BRPI0912227A patent/BRPI0912227A2/pt not_active IP Right Cessation
- 2009-05-06 CN CN2009801262812A patent/CN102088981B/zh not_active Expired - Fee Related
- 2009-05-06 RU RU2010150148/15A patent/RU2495668C2/ru not_active IP Right Cessation
- 2009-05-06 CA CA2723744A patent/CA2723744A1/en not_active Abandoned
- 2009-05-06 US US12/991,585 patent/US20110124579A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003090703A1 (de) * | 2002-04-25 | 2003-11-06 | Gaba International Ag | Mundpflegemittel enthaltend ovomucin |
Also Published As
Publication number | Publication date |
---|---|
BRPI0912227A2 (pt) | 2015-10-06 |
CA2723744A1 (en) | 2009-11-12 |
MX2010012253A (es) | 2010-12-17 |
CN102088981A (zh) | 2011-06-08 |
RU2010150148A (ru) | 2012-06-20 |
WO2009135867A1 (en) | 2009-11-12 |
AU2009245798A1 (en) | 2009-11-12 |
RU2495668C2 (ru) | 2013-10-20 |
US20110124579A1 (en) | 2011-05-26 |
EP2293799A1 (en) | 2011-03-16 |
EP2116139A1 (en) | 2009-11-11 |
JP2011519896A (ja) | 2011-07-14 |
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Facts | Probiotics and Prebiotics |
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