CN102948659A - 碳水化合物组合物 - Google Patents
碳水化合物组合物 Download PDFInfo
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- CN102948659A CN102948659A CN2012103820323A CN201210382032A CN102948659A CN 102948659 A CN102948659 A CN 102948659A CN 2012103820323 A CN2012103820323 A CN 2012103820323A CN 201210382032 A CN201210382032 A CN 201210382032A CN 102948659 A CN102948659 A CN 102948659A
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- carbohydrate
- oligosaccharides
- lactose
- dehydration
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Abstract
本发明涉及碳水化合物组合物,其包含:(a)3-40wt.%的纤维组合物,所述纤维组合物包含至少30wt.%的具有3-10个脱水单糖单位的寡糖,所述脱水单糖单位大部分是脱水吡喃糖单位,所述脱水吡喃糖单位选自半乳糖、甘露糖、木糖、它们的脱氧形式、氨基形式和N-酰氨基形式;(b)3-40wt.%的核糖和/或5-40wt.%的乳糖;和(c)20-80wt.%的其他可消化的碳水化合物,所述其他可消化的碳水化合物包括葡萄糖、麦芽糖糊精、淀粉、半乳糖、甘露糖、乳糖、海藻糖、帕拉金糖和异麦芽寡聚糖中的一种或多种。
Description
本申请是2006年12月18日提交的,发明名称为“可溶性膳食纤维对抗肌萎缩的用途”的中国专利申请200680052918.4的分案申请。
技术领域
本发明涉及包含难消化的寡糖的营养组合物或药物组合物用于治疗肌萎缩或降低其发病率的用途。
发明背景
严重的体重减轻且特别是肌萎缩是在患有疾病、病症和创伤的患者中大范围发生的严重现象。慢性疾病中的肌萎缩(简称MW)被定义为在一个月内体重自然减轻超过5%。如果以更缓的速率但在更长的时间内发生瘦体重(简称LBM)减轻,则本发明人指的是慢性肌萎缩(简称CMW),特别是如果在6个月内体重减轻超过10%。通常在创伤或手术的恢复中观察到MW。通常在严重疾病如癌症、AIDS、COPD、糖尿病和心力衰竭中观察到CMW。肌萎缩的速率与升高的发病率和死亡率相关。认为由疾病引起的肌萎缩的原因是多因素的。营养不良,特别是蛋白质-能量的营养不良也可能引起肌萎缩。如EP 0721742中提出的,通过提供额外的蛋白质或能量可以治疗或预防尤其是后一类型的营养不良。
少肌症(sarcopenia,简称SP)是伴随衰老发生的瘦肌肉质量、强度和功能的自然下降。SP增加了老人的功能性容量损失的风险,这不一定涉及疾病。
膳食纤维被频繁用于引发体重减轻。膳食纤维降低血液中的餐后葡萄糖水平并具有饱足感。因此,在营养不良、体重减轻和肌萎缩的情况下,一般不推荐给予大量膳食纤维。膳食纤维还被包含在用于影响结肠菌群的临床营养剂中,且已主张特定的纤维或其混合物降低全身性感染的速率(如在WO 02/26242中),提高特异性免疫相关的参数(如在EP-B 1105002中),或者降低动物中的选定肿瘤的生长速率(如在Taper H.,J Nutr.,129(1999),1488-1491中)。
许多类型的膳食纤维已被用于制备营养品。当存在于口中时,其中几种大大增加粘度,其他的具有差的溶解度或者产生沙样感觉。因此,需要这样的营养品,它们能容易地被患有肌萎缩或慢性肌萎缩的人们所消耗,并且对抗或预防肌萎缩,而没有现有技术的产品的缺点,如液体饮料的高粘度。
WO 2004/026294公开了游离的必需氨基酸(包括亮氨酸)的混合物用于改善肿瘤诱导的体重减轻的效果的用途。所述混合物可与其他成分如完整蛋白质、ω-3脂肪酸和可溶性纤维如水解的瓜尔胶混合。
US 6,387,883教导通过给药ω-3脂肪酸、支链氨基酸和可能包括膳食纤维的其他成分来治疗恶病质和厌食症。
US 2005/153019涉及通过提供包含乳清蛋白、ω-3脂肪酸、碳水化合物、维生素等的组合物来刺激机体的蛋白质合成。所述组合物还可以包含益生的纤维(例如果糖寡聚糖)用于促进双歧杆菌的生长,但这样的组合物未被进一步说明。
US 5,444,054教导在溃疡性结肠炎或绞痛炎症(colic inflammation)的情况下,使用ω-3脂肪酸EPA和DHA与难消化的碳水化合物(如***胶和果糖寡聚糖和木糖寡聚糖)的组合来改善营养状况的方法。
发明内容
令人惊讶地发现,包含至少30wt.%的难消化的寡糖的膳食纤维和包含这样的纤维的营养品或药品满足这种需要。这不同于现有技术中频繁使用纤维引发体重减轻。本发明所用的难消化的可溶性寡糖具有3-10个脱水单糖单位的链长。
在优选实施方案中,所述难消化的寡糖的脱水单糖单位大部分是脱水吡喃糖单位。这些脱水吡喃糖单位具有六元环结构,并包括醛糖的脱水形式如半乳糖、甘露糖、木糖以及它们的脱氧形式(例如岩藻糖和鼠李糖)、它们的酸形式如半乳糖醛酸酯和葡糖醛酸酯、它们的氨基形式和N-酰氨基形式(如半乳糖胺)、以及它们的更高级的同系物(例如神经氨酸和其他唾液酸)。它们还可以包括脱水葡萄糖单位及其衍生物,只要所述寡糖本质上仍是难消化的。因此,所述寡糖不含超过两个或优选少于两个α-1,4-连接的脱水葡萄糖单位。而且,所述寡糖中可存在少量其他脱水单糖单位,例如脱水***糖单位(无论是以吡喃糖苷形式还是呋喃糖苷形式)。通过在一个脱水单糖的第一(异头)碳原子与相邻脱水单糖部分的第2、3、4个(或在己糖的情况下为第6个)碳原子之间藉由氧原子的α-或β-连接可将所述脱水单糖单位彼此连接,正如已在本领域中对于许多难消化的碳水化合物中进行描述。
此实施方案的优选寡糖是半乳寡聚糖、甘露寡聚糖和/或木糖寡聚糖。它们可以是均聚寡糖,或者是包含半乳糖、甘露糖和/或木糖单位的异聚寡糖,所述异聚寡糖还可包含10-35%的脱水葡萄糖和/或脱水***糖单位、脱水岩藻糖、脱水葡萄糖胺和/或N-乙酰基-脱水葡萄糖胺单位,它们优选地在末端位置。尽管异聚体是有效的,但从成本有效的角度看,有时优选包括吡喃寡聚糖的同系物变体。在上下文中,仅在其末端位置具有单个不同单糖单位的寡糖(例如半乳寡聚糖中的葡萄糖单位)仍被认为是均低聚物(homo-oligomer)。
在另一实施方案中,所述难消化的寡糖的脱水单糖单位大部分是脱水呋喃糖单位。这些脱水呋喃糖单位具有五元环结构,并包括醛糖或酮糖的脱水形式如果糖或***糖、以及它们的脱氧形式、它们的氨基形式和N-酰氨基形式、以及它们的更高级的同系物。它们还可以包括脱水葡萄糖单位及其衍生物,只要所述寡糖本质上仍是难消化的。因此,这些寡糖不含超过两个或优选少于两个α-1,4-连接的脱水葡萄糖单位。而且,在这些寡糖中可存在少量其他脱水单糖单位,无论是以吡喃糖苷形式还是呋喃糖苷形式。
在本发明的另一优选实施方案中,所述寡糖由两类组成,一类大部分是脱水吡喃糖单位,另一类大部分是脱水呋喃糖单位,它们各自如上文所定义。在该实施方案中,所述膳食纤维包含至少40wt.%,优选至少50wt.%、更优选至少60wt.%的完全难消化的寡糖,所述完全难消化的寡糖包含30-98wt.%,优选50-96wt.%的第一类(吡喃糖系)寡糖和2-50wt.%,优选4-30wt.%的第二类(呋喃糖系)寡糖。这些重量百分数基于所述纤维组合物的重量。第一类和第二类之间的重量比优选为98:2至2:98,更优选97:3至10:90,最优选96:4至50:50。
可以通过本领域熟知的方法获得用于本发明的寡糖。根据第一种方法,可通过化学(酸)水解或优选酶法水解,将合适的多糖选择性地或随机水解。例如可以在pH 3-6,用β-甘露聚糖酶和/或α-半乳糖苷酶对瓜尔胶、刺槐豆胶、角豆树胶或他拉半乳甘露聚糖进行处理,以产生低粘度的产物,尤其是在通过α-半乳糖苷酶的作用从聚合物中除去部分或全部半乳糖时。作为另一实例,通过合适的(内-β-1,3-)半乳聚糖,任选地与***糖苷酶组合以除去***糖侧链,可将半乳聚糖和***半乳聚糖水解,并且使用(β-)木聚糖酶,任选地与***糖苷酶和/或半乳糖醛酸糖苷酶(galacturonidase)组合,可将木聚糖和***木聚糖(arabinoxylan)水解。通过选择适当的水解条件,可以获得具有需要链长的低粘度寡糖。通常,通过内型糖酵解水解,可以获得异聚寡糖如半乳糖基-低聚甘露聚糖、***糖基-低聚半乳聚糖和***糖基-低聚木聚糖,其中没有除去侧链,并且可以通过酶法除去侧链来获得大量均聚寡糖。在半乳甘露聚糖如瓜尔胶的水解产物的情况下,甘露二糖、甘露三糖和低聚半乳甘露糖的量优选超过所述寡糖的20%,优选为40-100%。作为进一步的实例,可以原样使用菊粉或者在化学水解或酶法水解后使用之;这样的水解得到具有末端葡萄糖单位的果糖寡聚糖和纯的果糖寡聚糖。
根据第二种通用方法,通过用一种或多种合适的酶或具有这些酶的一种或多种微生物或酵母将合适的底物酶法转糖基,可以制备(异聚)寡糖。合适的底物的实例为单己糖或二己糖、乳糖或纤维或它们的部分水解产物(如瓜尔胶的水解产物)的溶液。
特别地,半乳寡聚糖(GOS)非常适于制备有效的营养组合物或药物组合物。合适的半乳寡聚糖是可商购的,包括从乳糖通过与β-半乳糖苷酶反应制备的寡糖。优选地,这些半乳寡聚糖包含至少67wt.%,尤其是至少80wt.%的具有3至5个单位的链长的寡糖,无论是单糖还是二糖如乳糖。
对于体重80kg的人,所述可溶性膳食纤维组合物的有效剂量为0.1-20、优选0.6-10、更优选0.8-5克/剂。对于具有不同体重的人(包括婴儿),按比例降低所述剂量。关于每千克体重的剂量,优选的每日剂量为1.2-250mg/kg/天,优选7.5-130mg/kg/天,更优选10-65mg/kg/天。
所述可溶性纤维部分的其他成分可以包括非寡糖,如可溶的和可发酵的以及不可发酵的纤维,包括来自呋喃糖型的多糖。实例为菊粉、其他果糖多糖(果聚糖)、适度水解的果胶和其他树胶,如葡甘露聚糖(如Konjac)、半乳甘露聚糖(如瓜尔胶)、黄原胶和***胶。这些多糖(具有超过10个单位的链长(DP))可以占所述可溶性纤维组合物的高达70wt.%。然而,优选所述纤维组合物包含至少50%,更优选至少70%,高达例如95%或甚至98%或100%寡糖,尤其是上文定义的半乳寡聚糖、甘露寡聚糖、木糖寡聚糖。剩余部分可以由一种或多种可溶性多糖纤维(尤其是果聚糖型)组成。除了可溶性纤维部分,可以将不溶性纤维如抗性淀粉和不溶性可发酵的以及不可发酵的纤维如纤维素引入纤维掺混物中。优选的是,所述不溶性纤维占所述可溶性纤维部分的低于50wt.%,尤其在其5-25wt.%之间。
在具体实施方案中,所述可溶性纤维组合物可以包含2-50wt.%,特别是5-30wt.%的果聚糖(DP≥3)和/或2-35wt.%,特别是5-25wt.%的其他可溶性多糖,如水解的半乳甘露聚糖(具有超过10个脱水单糖单位)。
可被有益地包含在所述组合物中的其他成分是特异性蛋白质、脂质、碳水化合物和微量成分。
所述组合物可以是液体、半固体或固体。在液体溶液中,本发明的寡糖的引入得到非粘性的产品,当包含有效量时,在100sec-1剪切速率和20℃,具有低于70,优选1-40,更优选2-30MPa.s的粘度,这使得所述溶液适合用作管饲。在液体中,每个包装会包含有效剂量。对于管饲,假定为2000ml/天,每天分两部分给予。当所述液体产品用作补充剂时,例如以每份200ml,可相应计算浓度。通常,有效寡糖的浓度会大大低于15,例如0.05-10,优选0.5-9,更优选1-8%重量/体积。当所述产品为半固体形式如布丁或固体形式如棒时,所述产品会被用作补充剂,每个包装为25-200ml。因此所述浓度会为每25-200g产品0.1-20g。按能量计,所述可溶性纤维组合物的含量优选为每419KJ(100kal)0.5-10g,更优选每419KJ(100kcal)1-4g。
液体组合物的能量含量通常会为2.5-16.8,优选5.0-16.8,更优选5.4-8.4且最优选6.3-8.0KJ/ml(0.6-4.0,优选1.2-4.0,更优选1.3-2.0且最优选1.5-1.9kcal/ml)。
优选的是,本发明的营养组合物包含至少一种蛋白质部分。纤维部分与蛋白质部分之间的重量比优选为5:95至75:25,更优选为10:90至50:50。
基于总的氨基酸,蛋白质部分应优选包含超过45wt%,优选48-70wt%,更优选52-65wt%的必需氨基酸。必需氨基酸是甲硫氨酸、亮氨酸、异亮氨酸、缬氨酸、苯丙氨酸、色氨酸、组氨酸、赖氨酸和苏氨酸。液体产品中必需氨基酸的量通常会超过每100ml 4.75g,优选4.9-9.0g,更优选5.1-7g。
特别地,基于氨基酸的总和,优选亮氨酸+异亮氨酸的量超过18.0wt%,且更优选18.5-25wt%。亮氨酸的量优选超过11.0wt%,更优选超过11.4wt%,最优选为12.2-20wt.%。支链氨基酸的量通常会超过每100ml液体产品2.9g,优选3.0-4.0g,更优选3.0-3.4g。
蛋白质部分的能量贡献优选地为所述营养组合物的25-75en%,更优选26-60en%,最优选26-50en%。完整蛋白质部分的能量贡献优选地为所述营养组合物的17-40en%,更优选19-30en%,最优选20-29en%。所述蛋白质部分应该优选包含超过10%,更优选20-60%的完整乳清蛋白或其肽片段。
所述脂质部分应包含ω-3型长链脂肪酸。长链表示至少18个碳原子。特别优选的是具有20-26个碳原子并具有4个或更多个不饱和键的脂肪酸。长链多不饱和脂肪酸的总量应超过所有脂肪酸总和的10wt.%,优选15-50wt.%,更优选17-42wt.%,特别是18-42wt.%。ω-3长链多不饱和脂肪酸(LCP’s)(如:α-亚油酸、十八碳四烯酸、二十碳五烯酸(EPA)、二十二碳五烯酸(DPA)、二十二碳六烯酸(DHA)和二十四碳六烯酸(THA))与可溶性纤维之间的重量比优选为90:10至5:95,更优选80:20至15:85。长链多不饱和脂肪酸与可溶性纤维以及任选的其他成分的组合可被适当地用作食品补充剂。优选的是,所述可溶性纤维包含半乳寡聚糖、甘露寡聚糖和/或木糖寡聚糖,尤其是水平为例如可溶性纤维的至少50%w/w的半乳寡聚糖。所述脂质部分的能量贡献优选为营养组合物的15-45en%、更优选20-35en%。
所述碳水化合物部分可以包含葡萄糖、麦芽糖糊精、淀粉和/或其他糖。在优选实施方案中,所述碳水化合物部分包含5-50wt%的核糖、尤其是8-25wt.%的核糖以预防肌萎缩。基于所述可溶性纤维组合物,核糖优选以9:1至1:9,更优选4:1至1:4的重量比存在。该组合可以用作食品补充剂。优选的是,这样的补充剂还包含每份核糖1-19份的量的其他可消化的碳水化合物。在还包含脂质和/或蛋白质的营养组合物中,可消化的碳水化合物部分的能量贡献优选为组合物的15-55en%,更优选25-50en%。
还优选的是,所述碳水化合物部分包含乳糖。如果存在,那么乳糖的量超过所述可消化的碳水化合物部分的2wt.%,更优选3-40wt.%,最优选10-30wt%。有用的碳水化合物组合物可以包含3-40wt.%、优选5-30wt.%的如上文所述的可溶性纤维组合物和3-40wt.%,优选5-30wt.%的核糖和/或5-40wt.%,优选8-30wt.%的乳糖,以及优选20-80wt.%,更优选35-70wt.%的其他可消化的碳水化合物。
与现有技术的知识相反,为了实现降低肌萎缩速率或甚至增加体重,包含具有低升糖指数的可用碳水化合物部分是重要的。将可用碳水化合物部分定义为具有低升糖指数(GI),其值低于葡萄糖值的70%。所述碳水化合物部分应优选地包含超过20wt.%,更优选40-80wt.%的这些碳水化合物。低GI糖包括乳糖、海藻糖、异麦芽寡聚糖(大部分为α-1,6葡萄糖单位的寡糖)。
还优选包含少量甜糖以提高患者的食物消耗。甜度小于蔗糖甜度的70%的糖的量应超过可用碳水化合物部分的20wt.%。特别地,该量为25-60wt.%。低甜度的糖包括帕拉金糖(异麦芽酮糖)、麦芽糖糊精DE 2-47、半乳糖、甘露糖、乳糖和海藻糖。可选地,选自半乳糖、甘露糖、其他含有葡萄糖的二糖的低GI和/或低甜度糖比蔗糖和麦芽糖(包括乳糖、海藻糖和帕拉金糖)和异麦芽寡聚糖的总比例因此优选为20-80wt.%,更优选25-60wt.%。
通常包含人类适当进食所需的所有矿物质和微量成分。通常每日剂量包含推荐的每日量的0.5-1.5倍,除了以推荐的每日量的1-4倍包含叶酸类(尤其是300-1200μg/天或50-1000μg、尤其是60-600μg/g可溶性纤维)。
实施例1
材料和方法
使用雄性CD2F1小鼠(BALB/c x DBA/2,Harlan,荷兰),并用C-26腺癌细胞诱导荷瘤组(TB)的恶病质,而对照小鼠(C)接受假注射(shaminjection)。在试验1中,食物由51%半乳寡聚糖(GOS)和果糖多糖(9:1)、19%麦芽糖糊精、16%乳糖和14%葡萄糖组成。在试验2中,用另外的GOS代替FOS。反式半乳寡聚糖的GOS喷雾干燥粉末的聚合度(dp)为3-8(VivinalGOS,Borculo Domo,Zwolle,荷兰)且FOS具有高聚合度(Raftiline HP,Orafti,Wijchen,荷兰;平均dp>23)。在接种肿瘤细胞后,切除肿瘤块和骨骼肌(趾长伸肌(EDL)和比目鱼肌)并称重。
试验1
-对照小鼠 =C
-荷瘤小鼠 =TB
-荷瘤+GOS/FOS =TB-Gos Fos
试验2
-对照小鼠 =C
-荷瘤小鼠 =TB
-荷瘤+GOS =TB-Gos
结果
下表代表试验1和2的肌肉质量(mg,+相对于C的损失%)。
从本发明的数据中推断,半乳寡聚糖使得肿瘤恶病质中的肌肉损失变弱。星号(*)表示TB组的统计学差异(P<0.025)。
实施例2:
制备液体配方用于患有慢性肌萎缩的患者。其每100ml含有:
能量 658kJ(157kcal)
蛋白质[8.2g酪蛋白和乳清,1.8g Leu] 10.0g
脂质[海洋生物油(marine oil),植物性] 5.3g
a.EPA 0.56g
b.DHA 0.27g
碳水化合物 17.4g
a.蔗糖 4.21g
b.麦芽糖糊精 8.42g
c.海藻糖 4.21g
d.乳糖 0.59g
纤维 2.05g
a.菊粉DP>20 0.1g
b.水解的菊粉DP<20 0.08g
c.GOS 1.53g
d.抗性淀粉 0.05g
e.纤维素 0.31g
实施例3:
制备液体配方用于患有慢性肌萎缩的患者。该配方每100ml含有:
实施例4:
制备液体配方用于患有慢性肌萎缩的患者。该配方每100ml含有:
实施例5:
每100ml用于患有慢性肌萎缩的患者的液体配方含有:
Claims (10)
1.碳水化合物组合物,其包含
(a)3-40wt.%的纤维组合物,所述纤维组合物包含至少30wt.%的具有3-10个脱水单糖单位的寡糖,所述脱水单糖单位大部分是脱水吡喃糖单位,所述脱水吡喃糖单位选自半乳糖、甘露糖、木糖、它们的脱氧形式、氨基形式和N-酰氨基形式;
(b)3-40wt.%的核糖和/或5-40wt.%的乳糖;和
(c)20-80wt.%的其他可消化的碳水化合物,所述其他可消化的碳水化合物包括葡萄糖、麦芽糖糊精、淀粉、半乳糖、甘露糖、乳糖、海藻糖、帕拉金糖和异麦芽寡聚糖中的一种或多种。
2.权利要求1的碳水化合物组合物,其包含10-30wt%的所述可溶性纤维组合物(a)。
3.权利要求1的碳水化合物组合物,其包含40-80wt.%的低升糖指数糖,所述低升糖指数糖选自乳糖、海藻糖、异麦芽寡聚糖及其混合物。
4.权利要求1的碳水化合物组合物,其包含25-60wt.%的至少一种低甜度的糖,所述低甜度的糖选自帕拉金糖、麦芽糖糊精DE 2-47、半乳糖、甘露糖、乳糖和海藻糖。
5.权利要求1-4中任一项的碳水化合物组合物,其中所述纤维组合物(a)包含30-96wt.%的其中所述脱水单糖单位大部分是所述脱水吡喃糖单位的寡糖和4-50wt.%的其中所述脱水单糖单位大部分是脱水呋喃糖单位的寡糖和/或多糖,所述脱水呋喃糖单位选自果糖和***糖。
6.权利要求1-4中任一项的碳水化合物组合物,其包含(b)5-30wt.%的核糖和/或8-30wt.%的乳糖。
7.碳水化合物组合物,其包含10-90wt.%的如权利要求1所定义的纤维组合物(a)以及90-10wt.%的核糖。
8.食品补充剂,其包含权利要求1-7中任一项的碳水化合物组合物。
9.权利要求8的食品补充剂,其还包含一种或多种具有20-26个碳原子并具有4个或更多个不饱和键的ω-3脂肪酸,所述ω-3脂肪酸与所述可溶性纤维组合物之间的重量比为5-90:10-95。
10.食品组合物,其包含权利要求1-7中任一项的碳水化合物组合物和蛋白质部分。
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EP1965669B1 (en) | 2009-09-02 |
US9555059B2 (en) | 2017-01-31 |
ZA200805905B (en) | 2009-10-28 |
NZ569169A (en) | 2012-01-12 |
BRPI0619947B1 (pt) | 2023-10-10 |
CN101374426B (zh) | 2012-11-28 |
IL192219A (en) | 2011-08-31 |
RU2008129102A (ru) | 2010-01-27 |
AU2006325591B2 (en) | 2012-07-12 |
US20090203573A1 (en) | 2009-08-13 |
CA2633292C (en) | 2015-04-28 |
US20120165243A1 (en) | 2012-06-28 |
US8143235B2 (en) | 2012-03-27 |
IL192219A0 (en) | 2008-12-29 |
RU2450815C2 (ru) | 2012-05-20 |
ES2332149T3 (es) | 2010-01-27 |
CN102948659B (zh) | 2014-04-23 |
EP1965669A1 (en) | 2008-09-10 |
DE602006008985D1 (de) | 2009-10-15 |
ATE441333T1 (de) | 2009-09-15 |
AU2006325591A1 (en) | 2007-06-21 |
CN101374426A (zh) | 2009-02-25 |
CA2633292A1 (en) | 2007-06-21 |
JP2009519328A (ja) | 2009-05-14 |
WO2007069900A1 (en) | 2007-06-21 |
DK1965669T3 (da) | 2009-10-05 |
PL1965669T3 (pl) | 2010-02-26 |
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