CN101057853B - 抗粘附碳水化合物 - Google Patents
抗粘附碳水化合物 Download PDFInfo
- Publication number
- CN101057853B CN101057853B CN200710100849.6A CN200710100849A CN101057853B CN 101057853 B CN101057853 B CN 101057853B CN 200710100849 A CN200710100849 A CN 200710100849A CN 101057853 B CN101057853 B CN 101057853B
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- CN
- China
- Prior art keywords
- galacturonic acid
- carbohydrate
- acid
- galactooligosacchari
- few galacturonic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
本发明提供了用于减少和/或阻断病原物质和生物粘附到真核细胞、特别是哺乳动物细胞上的药物或食物制品。所述制品含有至少一种在其一端具有糖醛酸单元的抗粘附碳水化合物。所述碳水化合物上的末端糖醛酸单元中10-100%带有双键,该双键主要位于C4和C5原子间。
Description
本申请为国际申请PCT/EP01/01753于2002年8月16日进入中国国家阶段、申请号为01805223.1、发明名称为“抗粘附碳水化合物”的分案申请。
本发明涉及用于减少和/或阻断病原物质和生物粘附到真核细胞、特别是哺乳动物细胞上的药物或食物制品,其含有至少一种在一端具有糖醛酸的抗粘附碳水化合物,本发明还涉及所述制品和其中所含碳水化合物针对所述目的的应用。
病原生物和损伤细胞的物质粘附到哺乳动物细胞表面是感染或损伤细胞的第一步,也是必不可少的前提条件。病原体与细胞间的相互作用是通过配体-受体作用形成的,因此是病原体具有毒力或毒性的重要因素。至少应该理解细菌、病毒、真菌、单细胞寄生物或多细胞寄生物是病原体。在所述配体-受体作用中,糖结构具有重要的作用。
完全阻止或至少降低所述配体-受体作用的一种可能在于阻断细胞表面或配体上的各自受体。
使用特定的试验系统,可显示不同碳水化合物混合物减少或甚至完全阻止如微生物粘附到细胞表面,参见:Kunz,C;Rudloff,S.ActaPaediatr.1993,82,903-912。由此推断活性碳水化合物与受体或配体结构有相当大的相似性。在已描述的研究中,使用了多种来自动物和植物的碳水化合物以及植物多糖水解产物。
自然界中存在的碳水化合物以及如人奶碳水化合物的组成和结构非常复杂。而植物来源的碳水化合物以及植物多糖水解产物也同样复杂。这表明在大多数情况下碳水化合物对抗病原体粘附到哺乳动物细胞的作用是由碳水化合物混合物产生的,而非由纯化单一结构产生。
由此知道,例如来自多种植物产物的水性提取物和浆汁对于由致病微生物引起的肠道和尿生殖道疾病具有抗病活性。PCT/EP94/03006(WO95/07084)描述了利用根据确定方法制备的胡萝卜汤、狸藻茶汤(bladder tea)、椰奶等,大大减少致病微生物粘附于胃肠道和尿生殖道上皮细胞。推想是植物产物中存在的果胶产生上述作用,它们基本上是1,4-α-糖苷键合的半乳糖醛酸酐链。因此推想实际有活性的半乳糖醛酸酐符合多个标准,即确定的聚合度和甲基化程度。
本发明的目的在于显示利用碳水化合物,通过其与配体和/或真核细胞、特别是哺乳动物细胞表面结构相互作用,如何能有效减少或阻止病原体粘附。
根据权利要求所教导的内容,实现了所述目的。
本发明的主题特别是一种用于药物或食物制品,其含有至少一种在一端具有糖醛酸单元的抗粘附碳水化合物。众所周知,碳水化合物至少具有两个末端,当具有支链时,甚至可具有三个或更多末端。根据本发明,直链碳水化合物和支链碳水化合物都可使用。在这些末端中的一个上面,存在具有可酯化末端COOH基团的所述糖醛酸。优选的糖醛酸或糖醛酸单元是如下游离或酯化的酸:半乳糖醛酸、葡萄糖醛酸、古洛糖醛酸、艾杜糖醛酸、甘露糖醛酸、核糖醛酸和阿卓糖醛酸,特别优选半乳糖醛酸和葡萄糖醛酸。
本发明制品含有至少一种抗粘附碳水化合物,即一种在一端具有糖醛酸单元的确定物质。但本发明制品也可含有数种具有末端糖醛酸单元的抗粘附碳水化合物。本发明制品可适当地含有由若干该抗粘附碳水化合物组成的混合物。
应理解在本文件中,抗粘附碳水化合物具有末端糖醛酸单元,且明确地说,不依赖于该糖醛酸单元是否具有双键。换言之,术语“抗粘附碳水化合物”指具有以双键为特征的糖醛酸的碳水化合物以及具有糖醛酸单元但不带双键的碳水化合物的总和。本发明的基本思想在于使用这样的抗粘附碳水化合物,其具有最小量的带双键糖醛酸。
抗粘附碳水化合物可具有确定的聚合度,一般缩写为DP,在本文中也如此。但通常存在不同聚合度的抗粘附碳水化合物,确定聚合度的抗粘附碳水化合物可能以多种方式组成。换言之,本发明制品含至少一种在一端具有糖醛酸单元的确定抗粘附碳水化合物。这种碳水化合物当然具有确定的聚合度。此外,可存在若干具有相同聚合度的组成不同的抗粘附碳水化合物。另外,可存在具有不同聚合度的抗粘附碳水化合物,因此对于各聚合度,可存在一种或若干种抗粘附碳水化合物。
对在一端具有糖醛酸单元的上述抗粘附碳水化合物的具体定义中,不对构成这些抗粘附碳水化合物的其他糖类单元或单体单元的性质进行任何描述,除抗粘附碳水化合物只由一个单一单元(聚合度即DP为1)即一个糖醛酸单元构成之外。当抗粘附碳水化合物DP为1时它仅由该类一个糖醛酸单元构成。如果抗粘附碳水化合物DP为2或更高,则与糖醛酸单元连接的其他糖类单元可为任何合乎需要的单元。
所述碳水化合物上的糖醛酸单元中10-100%必须带有双键。因此,%数值表示存在于所述碳水化合物一端上的所有带双键糖醛酸单元的数目,其中所述糖醛酸单元指在抗粘附碳水化合物一端上的带双键糖醛酸单元和可能存在的不带双键糖醛酸单元的总和。
顺便提及,在抗粘附碳水化合物一端上的糖醛酸单元在此也称作末端糖醛酸单元。
根据本发明使用的抗粘附碳水化合物在一端具有糖醛酸单元,它们在另一端(不带支链的情况下)可能具有非还原性糖单元,也可能具有还原糖单元。带末端糖醛酸单元的抗粘附碳水化合物中优选10-100%在另一端(直链)或其他末端之一(带支链情况)具有还原糖单元。换言之,10-100%末端糖醛酸单元位于非还原端。因此,所有末端糖醛酸单元都可能存在于非还原端。
50-100%的双键优选位于末端糖醛酸单元的C4-C5原子之间。在这种情况下,%数值表示双键数目,与抗粘附碳水化合物的聚合度及形成这些抗粘附碳水化合物的糖单元无关。可在235nm下使用55001/molcm摩尔消光系数经分光光度法测定双键并由此测定带双键末端糖醛酸单元,参见TP Kravtchenko,I.Arnould,AGJ Voragen&W.PolnikCarbohydr.Polymer1992,19,237-242。
带还原端碳水化合物的测定根据如下文献的描述用碘量法进行:Analytical Chemistry of Carbohydrates,H.Scherz,G.Bonn,EditorThieme Organic Chemistry Monograph Series,Stuttgart,New York,Thieme Publishers1998,第32页。仅带非还原端的碳水化合物的测定可使用常规分析方法如渗透压测定法、质谱分析法(例如MALDI-MS,ESI-MS)、色谱法(例如GPC、HPAEC,HPLC)和毛细管电泳或者这些方法的组合。
除末端糖醛酸单元外,根据本发明使用的抗粘附碳水化合物还可具有非还原端,即,例如还原端随后转化成非还原端。这可通过例如氧化、还原或将还原端连到其他分子上来实现。所述其他分子包括例如蛋白、脂质和工业聚合物,通过它们得到(新)葡糖偶联物。随后对还原端的修饰不影响本发明使用的抗粘附碳水化合物的抗粘附作用。这些抗粘附碳水化合物由此也可通过“前”还原端固定到已知载体如常规载体上。
当10-100%的末端糖醛酸单元具有双键时,当然还意味着0-90%的末端糖醛酸单元不具有双键。抗粘附碳水化合物的末端糖醛酸单元中优选有10-50%具有这样的双键。
与先前提及的WO95/07084的教导不同,惊奇地发现即便是对于该文献中描述的可能具有抗粘附作用的碳水化合物,聚合度和甲基化程度均不产生显著抗粘附作用。而具有带双键末端糖醛酸单元的碳水化合物具有显著抗粘附作用。但是,这些抗粘附碳水化合物,尤其是那些糖醛酸单元在C4和C5原子间存在双键的抗粘附碳水化合物,不能根据WO95/07084的教导获得,这将在下文中具体讨论。
根据本发明考虑指定聚合度的抗粘附碳水化合物时,可能只涉及一种单一的抗粘附碳水化合物。但也可考虑若干不同结构的抗粘附碳水化合物,它们的共同特点其一是指定聚合度,其二是末端糖醛酸单元。
优选本发明制品不但包括一种或若干具有指定DP的抗粘附碳水化合物,也包括若干不同聚合度的抗粘附碳水化合物。所使用的抗粘附碳水化合物的聚合度优选为DP2至DP40,特别优选DP2至DP10,最高为DP100。优选使用具有不同链长的抗粘附碳水化合物的混合物。在这种情况下,可考虑仅一种单一碳水化合物或若干碳水化合物,或者任何需要的抗粘附碳水化合物组合,其中所述抗粘附碳水化合物具有确定的链长或指定的聚合度。
特别是在非还原端具有末端糖醛酸单元并具有双键的抗粘附碳水化合物具有增强的抗粘附作用。在本文件中,这些抗粘附碳水化合物也可指定为不饱和碳水化合物。
通过用酶切或化学切割酸性碳水化合物和优选含糖醛酸碳水化合物可获得本发明使用的抗粘附碳水化合物和不饱和抗粘附碳水化合物,并以此方式得到指示含量的含有双键的糖醛酸单元。如下物质可用作优选的起始碳水化合物:果胶、果胶酸盐、藻酸盐、软骨素、透明质酸、肝素、类肝素、细菌碳水化合物和其他含糖醛酸碳水化合物。在这种情况下优选的原料是植物和/或植物的部分,例如胡萝卜、柑橘类水果、甜菜和苹果,参见C.Rolin,BU Nielsen & PE Glahn,《Polysaccharides》,S.Dimitriu,Marcel Dekker编辑,New York,1998。也可使用海藻、动物组织和细菌产物。
当经化学切割制备不饱和抗粘附碳水化合物时,上述情况也同样适用,以便经β-消除来引入双键,例如在中性或弱碱性条件下裂解果胶,参见MJH Keijbets&W.Pilnik,Carbohydr.Res.1974,33,359-362。
酶切特别可通过裂解酶(例如果胶溶酶或果胶酸盐裂解酶)或含裂解酶的酶制剂进行。
对于化学切割,在中性至碱性条件下进行,以便得到所需含量的双键。通过适当选择其他参数如温度、pH和缓冲液浓度,还可影响羧基和/或羟基的酯化程度。所用起始化合物(如果胶)的酯化程度较高时,在弱酸性范围内进行切割,可类似地获得本发明使用的抗粘附碳水化合物,由此也可得到不饱和抗粘附碳水化合物。
当羧基成甲酯以及形成乙酰酯时,例如在糖醛酸C-2和/或C-3原子上形成时,也可影响不饱和抗粘附碳水化合物的抗粘附作用。这特别适用于果胶的半乳糖醛酸。甲基化或乙酰化程度优选为20-75%,特别优选20-50%。
如前所述,特别位于非还原端的糖醛酸单元的双键对于本发明优选使用的抗粘附碳水化合物混合物特别重要。与带双键或甚至无双键的所述糖醛酸单元相连的其他糖单元可仅为酸性碳水化合物单元,仅为中性碳水化合物单元,或者酸性和中性碳水化合物单元的混合物。也即中性碳水化合物单元影响不饱和抗粘附碳水化合物的抗粘附作用。因此,主要考虑鼠李糖、阿拉伯糖、半乳糖、木糖、葡萄糖、果糖和芹菜糖,它们可与feroyl残基及酚类物质相连。这特别使用于果胶。中性碳水化合物单元部分优选达到最高50%,特别优选为0-30%。
所用抗粘附碳水化合物或抗粘附碳水化合物混合物的抗粘附作用不依赖于终产物浓度,而依赖于所加的量。因此,本发明制品可仅由抗粘附碳水化合物或抗粘附碳水化合物混合物组成。为此,所述制品例如被制成片或食物增补剂。当然,对于药物制品,可使用常规可药用载体、稀释剂和/或辅药。这些抗粘附碳水化合物也可掺入任何含其他成分的目的食物或药物制品中。对于食物,可考虑脂肪、蛋白、矿物、微量元素、维生素和其他适合食品生产的材料。此外,可将本发明抗粘附碳水化合物与具有任何所需特性的其他碳水化合物一同使用。
根据优选的实施方式,所涉及的其他碳水化合物是如WO00/08948和国际申请PCT/EP99/05878所述的益生素()碳水化合物混合物,因此涉及由两种不同的基本可溶的碳水化合物组分A和B组成的益生素碳水化合物混合物,这两种碳水化合物组分在胃肠道中保持不被消化,在到达大肠时是未被吸收的,其中所述碳水化合物组分A由至少一种单糖,或至少一种寡糖(二糖至六糖),或者两种或几种这样的糖的混合物组成,所述碳水化合物组分B由一种多糖(七糖以上),或者两种或几种多糖的混合物组成,基于碳水化合物组分总和A+B(=100重量%),所述碳水化合物组分A为5-95重量%,所述碳水化合物组分B为5-95重量%,并且碳水化合物/碳水化合物组分A和B的糖类中至少80重量%具有益生素活性。但为本发明的目的,只有不为含糖醛酸抗粘附碳水化合物的碳水化合物才可构成碳水化合物组分A和碳水化合物组分B。因此,组分A和B不属于任何抗粘附碳水化合物。在下文中为简化,将这些构成碳水化合物组分A和碳水化合物组分B的碳水化合物称为益生素碳水化合物,尽管这些碳水化合物中实际上只有一部分是具有益生素活性的。
碳水化合物组分A和B总计的称为益生素的碳水化合物或糖类中至少80重量%具有益生素活性。优选在碳水化合物组分A中至少80重量%称为益生素的碳水化合物和在碳水化合物组分B中至少80重量%称为益生素的碳水化合物具有益生素活性。换言之,在各种情况下,优选在碳水化合物组分A和B中至少80重量%称为益生素的碳水化合物或糖类在到达大肠时一定未被消化(因此在小肠中不可吸收)。换言之,在碳水化合物组分A和B中的碳水化合物或糖类在胃肠道中没有被吸收和消化,在胃中没有,在小肠中也没有,并以此状态到达大肠。
应理解,室温下浓度至少1g/l时,碳水化合物组分A和B中的可溶碳水化合物(例如根据Roempps Chemie Lexikon)从物理意义上可在水中形成均相溶液。
碳水化合物组分A和B中不具有益生素活性的碳水化合物或糖类部分最高占20重量%。这些碳水化合物或糖类确实是可溶的,但可以以未消化形式排泄。因其增加排泄物体积或因其具有水结合作用,这些碳水化合物可产生生理作用。
构成碳水化合物组分A的益生素碳水化合物/糖类与构成碳水化合物组分B的益生素碳水化合物/糖类优选具有不同的结构。更优选碳水化合物组分A和B的益生素碳水化合物/糖类中至少有80重量%易受乳酸菌和/或双歧杆菌的作用。在这种情况下,碳水化合物组分A的重量百分率优选大于碳水化合物组分B的重量百分率。基于A+B=100重量%,碳水化合物组分A构成优选为95-60重量%,特别优选为约90重量%,而碳水化合物组分B构成优选为5-40重量%,特别优选为约10重量%。碳水化合物组分A和B的益生素碳水化合物/糖类尤其不具有任何以α1-4和/或α1-6键合的葡萄糖单元。在这种情况下,碳水化合物组分B的益生素碳水化合物/糖类优选由最多为100单糖单元构成。
碳水化合物组分A的益生素碳水化合物/糖类还优选有至少60重量%,特别优选有80-100重量%属于半乳寡糖,碳水化合物组分B的益生素碳水化合物/糖类优选有至少60重量%,特别优选有80-100重量%属于果聚糖。
当这类益生素碳水化合物混合物存在于本发明制品中时,抗粘附碳水化合物与益生素碳水化合物混合物的重量比优选为1:99至99:1,特别优选为1:10至10:1,更优选为约1:1。
此外,除了抗粘附碳水化合物和可能存在的益生素碳水化合物混合物,在本发明制品中还可存在任何所需种类的其他常规碳水化合物。在这种情况下可考虑不溶性碳水化合物、可溶并可消化的碳水化合物、主要用作营养目的的常规碳水化合物(例如淀粉、麦芽糖糊精、乳糖和蔗糖)或者一种或几种所述这些碳水化合物的混合物。这些情况下使用的抗粘附碳水化合物构成优选为0.1-30重量%,特别优选1-10重量%。
使用抗粘附寡糖,导致病原物质不与哺乳动物细胞结合,或者使已结合的病原体脱附。加入益生素寡糖,可消除通常由病原体引起的肠道菌群功能障碍。此外,已均衡的肠道菌群经全身性作用可抵抗在胃肠道以外其他地方的病原体,例如在尿生殖道、呼吸道、血液系统和皮肤中的病原体。
由于病原体粘附是其感染或毒害哺乳类生物所有细胞的必要前提,因此本发明使用的抗粘附碳水化合物不仅可用于预防或减轻胃肠道中的感染或损害,更可用于所有细胞中。
因此,本发明的主题也是将本发明制品和其中所含抗粘附碳水化合物用于防止或减少病原体粘附到真核细胞、特别是哺乳动物细胞。这些碳水化合物优选用于治疗胃肠道、血液系统、呼吸道、尿生殖道、鼻咽管感染,并用于治疗毒素或重金属阳离子对胃肠道、血液系统、呼吸道、尿生殖道、鼻咽管细胞的损害。因此,本发明的主旨也是将抗粘附碳水化合物用于制备上述治疗用途的食物或药物制品。
顺便提及,所述应用并不限于经肠道给药的食物或药物制品。相反,本发明使用的抗粘附碳水化合物还可作为活性成分用在经非肠道给药的药物制品中。因此,对于本发明制品,可考虑使用这样的经非肠道给药的药物产品。
本发明使用的抗粘附碳水化合物量,包括具有不带双键末端糖醛酸单元的碳水化合物及具有带双键末端糖醛酸单元的碳水化合物(不饱和碳水化合物)总计用量是至少8mg/kg体重·天,优选8-20mg/kg体重·天,特别优选约10mg/kg体重·天,其中所述具有带双键末端糖醛酸单元的碳水化合物中10-100%末端糖醛酸单元具有双键。这一数据特别是针对仅优选不饱和抗粘附碳水化合物的情况。
对于本文件中使用的范围,例如%范围或mg范围,所有中间值即位于端点值之间的所有值,以及由这些范围所覆盖的所有较窄范围也都已被公开并要求保护这些数值范围。因此,所表示的8-20mg/kg覆盖了所有的中间值,特别是整数值,例如9、10、11、12、13、14、15、16、17、18、19mg/kg。因此,所表示的范围10-100%只是缩写,表示所有可想象的中间值,特别是整数值11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98和99%。此用于例如带双键糖醛酸单元百分率的%表示法。该表示法还类似地覆盖并公开了所有可想象的较窄范围。所有涉及重量%、DP或其他单位的范围表示法同样适用。
在如下实施例中,描述了优选的本发明制品。实施例1-7涉及含有至少10%带双键糖醛酸单元的抗粘附碳水化合物的制备。在这种情况下得到的产物是仅由抗粘附碳水化合物组成的制品。实施例8-13描述了不同重量比的抗粘附碳水化合物和益生素碳水化合物混合物的混合物。
实施例1(酶切)
10g GENU果胶USP/100(Hercules Co.,Copenhagen,DK)溶于1升50mM NaOAc缓冲液(pH5.0)中。向该溶液中加入10ml果胶溶酶液(Sigma,Deisenhofen)。在40℃转化24小时。加热至100℃保持10分钟,使反应终止。用50kDa滤膜滤除酶和未转化的果胶。然后将滤液冻干。
实施例2(化学切割)
10g GENU果胶USP/100(Hercules Co.,Copenhagen,DK)溶于1升0.2M的碳酸铵缓冲液(pH6.8)中80℃加热8小时。得到的寡半乳糖醛酸酐以金属盐形式(例如钡盐)沉淀,过滤,洗涤,干燥,利用DOWEX-50H+离子交换剂转化为游离酸,并冻干。
实施例3(酶切)
10g Laboron果胶X-77A(C.C.A.Klimmeck,Bad Zwischenahn)溶于1升50mM NaOAc缓冲液(pH4.5)中。用1ml果胶溶酶液(Gist-Brocades Co.,Seclin,France)在45℃消化24小时。加热至95℃保持5分钟,使反应终止。用BioGel P2或TosoHaas HW40S凝胶过滤去除酶和未转化的果胶。然后将寡糖级分冻干。
实施例4(酶切)
10g Gruenband果胶(Obipektin,Bischofszell,Switzerland)溶于1升50mM NaOAc缓冲液(pH4.5)中。加入2ml Pentinex3XL(NovoNordisk Co.,Dittingen,Switzerland)。反应液加热至50℃保持24小时。随后加热至95℃保持5分钟,使反应终止。生成的寡半乳糖醛酸酐用乙醇沉淀,洗涤并干燥。
实施例5(化学切割)
10g Gruenband果胶(Obipektin,Bischofszell,Switzerland)溶于1升0.1M的磷酸钠缓冲液(pH6.8)中加热至90℃保持1小时。生成的寡半乳糖醛酸酐用乙醇沉淀,洗涤并干燥。
实施例6(化学切割)
10g GENU果胶USP/100(Hercules Co.,Copenhagen,DK)溶于1升0.1M的磷酸钠缓冲液(pH6.8)中加热至95℃保持1小时。长链聚合物用pH2的盐酸沉淀,离心后取出。含寡半乳糖醛酸酐的上清液冻干。
实施例7(酶切)
10g藻酸盐溶于1升50mM NaOAc缓冲液(pH4.6)中。向该溶液中加入10ml藻酸盐裂解酶液。在40℃切割24小时。加热至100℃保持10分钟,使反应终止。用50kDa滤膜滤除酶和未转化的果胶。然后将滤液冻干。
实施例8-13
为制备除抗粘附碳水化合物外还含有益生素碳水化合物的制品,进行如下步骤:
根据实施例1、3、4和/或7中任一例酶切制得或者根据实施例2、5和/或6中任一例化学切割制得的10g寡半乳糖醛酸酐,在进行干燥前,按照下表中列出的重量比掺和到10g益生素碳水化合物混合物中并与之混合,所述混合物的组成为9份半乳寡糖(例如,Elixor,BorculoCo.,和Oligomate,Yakult Co.)和1份高分子菊粉(例如,Raftiline HP,Orafti Co.或Frutafit TEX或EXL.,Sensus Co.或Fibruline LC HAT,Cosucra Co.)。
除上述半乳寡糖和菊粉的益生素碳水化合物混合物外,还可使用由如下组分组成的碳水化合物混合物:
α-半乳寡糖和菊粉,β-半乳寡糖和半乳甘露聚糖,果寡糖和半乳甘露聚糖,果寡糖和阿拉伯半乳聚糖,β-半乳寡糖和阿拉伯半乳聚糖,以及木寡糖和半乳甘露聚糖。
Claims (27)
1.一种药物制品,其含有在其一个末端上具有末端糖醛酸单元的寡半乳糖醛酸,
其中所述寡半乳糖醛酸的聚合度最大为DP 100,
所述寡半乳糖醛酸上存在的末端糖醛酸单元中有10-100%带有双键,并且
50-100%的所述双键位于末端糖醛酸单元的C4和C5原子之间,
其中所述寡半乳糖醛酸与甲醇酯化的程度为20-50%,
并且另外含有半乳寡糖和果聚糖。
2.权利要求1的药物制品,其中所述寡半乳糖醛酸中有10-100%包含还原端,并在另一端包含末端糖醛酸单元。
3.权利要求1的药物制品,其中所述寡半乳糖醛酸的末端糖醛酸单元中有10-50%具有双键。
4.权利要求1的药物制品,其中所述半乳寡糖由二糖至六糖组成以及所述果聚糖由七糖以上组成。
5.权利要求1的药物制品,其中所述寡半乳糖醛酸的聚合度为DP 2至DP 40。
6.权利要求5的药物制品,其中所述寡半乳糖醛酸的聚合度为DP 2至DP 10。
7.权利要求1的药物制品,其中所述寡半乳糖醛酸的含量以中性糖单元计最大为50%。
8.权利要求7的药物制品,其中所述寡半乳糖醛酸的含量以中性糖单元计为0-30%。
9.权利要求1的药物制品,其中基于半乳寡糖和果聚糖的总和,所述半乳寡糖为5-95重量%以及所述果聚糖为5-95重量%。
10.权利要求9的药物制品,其中所述寡半乳糖醛酸与半乳寡糖和果聚糖的重量比为1∶99至99∶1。
11.权利要求10的药物制品,其中所述寡半乳糖醛酸与半乳寡糖和果聚糖的重量比为1∶10至10∶1。
12.权利要求11的药物制品,其中所述寡半乳糖醛酸与半乳寡糖和果聚糖的重量比为1∶1。
13.权利要求1的药物制品,其中其含有常规可药用载体、稀释剂和/或其他辅药。
14.一种食物制品,其含有在其一个末端上具有末端糖醛酸单元的寡半乳糖醛酸,
其中所述寡半乳糖醛酸的聚合度最大为DP 100,并且
所述寡半乳糖醛酸上存在的末端糖醛酸单元中有10-100%带有双键,
50-100%的所述双键位于末端糖醛酸单元的C4和C5原子之间,
其中所述寡半乳糖醛酸与甲醇酯化的程度为20-50%,
并且另外含有半乳寡糖和果聚糖。
15.权利要求14的食物制品,其中所述寡半乳糖醛酸中有10-100%包含还原端,并在另一端包含末端糖醛酸单元。
16.权利要求14的食物制品,其中所述寡半乳糖醛酸的末端糖醛酸单元中有10-50%具有双键。
17.权利要求14的食物制品,其中所述半乳寡糖由二糖至六糖组成以及所述果聚糖由七糖以上组成。
18.权利要求14的食物制品,其中所述寡半乳糖醛酸的聚合度为DP 2至DP 40。
19.权利要求18的食物制品,其中所述寡半乳糖醛酸的聚合度为DP 2至DP 10。
20.权利要求14的食物制品,其中所述寡半乳糖醛酸的含量以中性糖单元计最大为50%。
21.权利要求20的食物制品,其中所述寡半乳糖醛酸的含量以中性糖单元计为0-30%。
22.权利要求14的食物制品,其中基于半乳寡糖和果聚糖的总和,所述半乳寡糖为5-95重量%以及所述果聚糖为5-95重量%。
23.权利要求22的食物制品,其中所述寡半乳糖醛酸与半乳寡糖和果聚糖的重量比为1∶99至99∶1。
24.权利要求23的食物制品,其中所述寡半乳糖醛酸与半乳寡糖和果聚糖的重量比为1∶10至10∶1。
25.权利要求24的食物制品,其中所述寡半乳糖醛酸与半乳寡糖和果聚糖的重量比为1∶1。
26.权利要求14的食物制品,其中其含有常规食物成分。
27.权利要求26的食物制品,其中所述常规食物成分选自维生素和微量元素。
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DE10006989.4 | 2000-02-16 | ||
DE10006989A DE10006989A1 (de) | 2000-02-16 | 2000-02-16 | Antiadhäsive Kohlenhydratmischung |
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US (4) | US20030022863A1 (zh) |
EP (3) | EP1267891B1 (zh) |
JP (1) | JP4965043B2 (zh) |
CN (2) | CN101057853B (zh) |
AT (1) | ATE517628T1 (zh) |
AU (2) | AU2001246441B2 (zh) |
BR (1) | BR0108354B1 (zh) |
CA (2) | CA2400244C (zh) |
CY (1) | CY1111968T1 (zh) |
CZ (1) | CZ20022702A3 (zh) |
DE (1) | DE10006989A1 (zh) |
DK (1) | DK1267891T3 (zh) |
ES (1) | ES2370478T3 (zh) |
HK (1) | HK1053986A1 (zh) |
HU (1) | HUP0300409A3 (zh) |
IL (1) | IL151274A (zh) |
MX (1) | MXPA02007970A (zh) |
NO (2) | NO331735B1 (zh) |
NZ (1) | NZ520642A (zh) |
PL (1) | PL204585B1 (zh) |
PT (1) | PT1267891E (zh) |
RU (1) | RU2267324C2 (zh) |
SK (1) | SK288087B6 (zh) |
TR (1) | TR200202008T2 (zh) |
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EP1723951A1 (en) * | 2005-04-21 | 2006-11-22 | N.V. Nutricia | Nutritional supplement with oligosaccharides for a category of HIV patients |
CA2570208A1 (en) * | 2004-06-22 | 2005-12-29 | N.V. Nutricia | Improvement of barrier integrity in hiv patients |
EP1721611A1 (en) * | 2005-04-21 | 2006-11-15 | N.V. Nutricia | Nutritional supplement with oligosaccharides for a category of HIV patients |
EP1634599A1 (en) | 2004-08-20 | 2006-03-15 | N.V. Nutricia | Iimmune stimulatory infant nutrition |
DE602004006258T3 (de) | 2004-08-24 | 2013-08-29 | Nutricia N.V. | Nahrungszusammensetzung die unverdauliche Transgalaktooligosaccharide sowie verdauliche Galaktose-Saccharide enthält |
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BRPI1011248A2 (pt) | 2009-06-03 | 2016-03-22 | Algipharma As | métodos in vitro ou ex vivo de superação de resitência a pelo menos um antibiótico, para combate de contaminação de um sítio e melhora da eficácia de um antibiótico de macrolídeo para inibir o crescimento de bactéria mdr gram negativa, uso de um oligômero de alginato e produto |
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2000
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- 2001-02-16 EP EP01919291A patent/EP1267891B1/de not_active Expired - Lifetime
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