CN1620257B - 包含果胶的基质形成组合物 - Google Patents
包含果胶的基质形成组合物 Download PDFInfo
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- CN1620257B CN1620257B CN028282574A CN02828257A CN1620257B CN 1620257 B CN1620257 B CN 1620257B CN 028282574 A CN028282574 A CN 028282574A CN 02828257 A CN02828257 A CN 02828257A CN 1620257 B CN1620257 B CN 1620257B
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- calcium
- oligosaccharides
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Abstract
本发明一方面涉及一种液体可食用的组合物,其pH大于6,粘度在剪切速率为100s-1和20℃时低于600mPas,以及粘度在温度为37℃和pH低于5时至少为前述粘度的125%。该组合物包含至少0.05重量%的甲氧基化程度在2到50之间的果胶和/或藻朊酸盐;每100ml至少5mg钙;以及至少0.1重量%聚合度在2和60之间的不消化寡糖。本发明的另一个方面涉及一种用于预防或治疗哺乳动物的过重或肥胖方法,所述方法包含对哺乳动物肠内给予有效量的前述组合物。
Description
技术领域
本发明涉及一种组合物,其在大约中性pH值时为液态,在低pH时形成一种粘性的基质,该组合物包含果胶、钙和寡糖。本发明的组合物特别适用于一种治疗或预防过重或肥胖方法。因此本发明也可以包含一种治疗哺乳动物过重或肥胖的方法,该方法包含通过肠道(如口服)施用有效量的前述化合物。
背景技术
肥胖是主要的健康问题,在美国大约有97,000,000人在临床上被认为过重。
已经提出各种化学治疗方法用来控制肥胖。食欲抑制剂如右旋安非他命,非安非他命类药物酚妥拉明和氟苯丙胺(Phen-Fen)的联合应用,以及单独使用右芬氟拉明(Redux),都存在着严重的副作用。不消化的物质如olestra、矿物油或新戊(烷)基酯类都被认为是食用脂肪的替代品。藤黄酸及其衍生物被认为通过干扰脂肪酸的合成来治疗肥胖症。外科手术技术,如暂时的回肠改道术,在一些极端的病例中得到应用。
然而,如上所述的治疗肥胖症的方法都有严重的缺点。控制饮食是控制肥胖最流行的技术,因此需要新的适于治疗肥胖的组合物。身体脂肪的蓄积和保持和热量的摄取直接相关。因此,控制体重战胜肥胖的最通用的方法之一就是采用低脂肪高纤维的饮食。特别是高粘性的纤维在抗肥胖饮食中被优先采纳。在摄入足够量时,高粘度的纤维可以诱发过饱的感觉。
JP2000189109描述了一种预防和治疗肥胖症的食物组合物,其在胃中有较长的滞留时间,它适用于肥胖症和/或糖尿病的治疗并在低pH时变为凝胶样物质。组合物含有酯化程度为40%或更少的可溶性纤维,该产品不包含钙和寡糖。
US4784861描述了一种包装的控制体重的粉末,可用作在吃饭前使用的食物添加剂,每个包装包含在所吃的食物上喷撒的剂量。粉末是由燕麦、小麦和玉米麸皮以及果胶、瓜尔豆树胶、车前草和角质混合组成。矿物补充剂用来代替由麸皮纤维排除的物质。该粉末在低于50%的湿度的空气中制备,并以相对小的尺寸包被在独立的防水包装中。
此外,包含果胶的制剂也可在例如用作药物中的载体,以缓慢释放生物活性物质,如抗酸剂组合物和抗肠胃气胀药组合物。
WO9633694描述了一种果胶制剂,其包含至少一种果胶及一种复合组合物,该复合组合物首先包含一种容易在水中分散果胶、水化和调节与悬浮水的硬度无关的凝胶化过程的泡腾剂组合,其次包含在酸性介质中为凝胶形成提供必须的钙离子的化合物与调整钙离子有效性动力学的镁离子的混合物。
WO9959542描述了一种果胶制剂,可以用作能够口服并在酸性介质中形成凝胶的药物载体,包含至少一种甲氧化的程度高于15%的果胶和钙离子,包含一种pH高于6的凝胶过程抑制剂。该果胶制剂不包含寡糖。
US5068109涉及一种用具有流动性的抗酸组合物,以及一种治疗或减轻上部胃肠道消化不良的病症,该抗酸组合物包含一种物质a),其在中性或碱性pH中是可溶的,但能在酸性pH时形成一种粘合性凝胶;一种能够被由物质a)在酸性pH时形成的凝胶结构中的物质以及一种或多种可捕获于由物质a)在酸性pH时形成的凝胶结构中的酸性中和剂,其中至少一种物质能够在和酸接触时使得凝胶起泡。物质a)可以是一种低甲氧基化的果胶或一种酰胺化的果胶复合物。该抗酸组合物缺乏寡糖。
发明内容
上述包含果胶的组合物对于治疗肥胖症或过重不是很适合的,主要是因为其对钙的生物利用度的不希望有的影响,和/或在胃中低pH中形成的果胶基质的粘性不足。本发明提供了一种解决上述问题的方法。
本发明提供了一种组合物,包含果胶和/或藻朊酸盐、钙和寡糖。本组合物是液态的(在中性pH左右)并在酸性pH时因为粘性基质的形成表现出粘性升高。在摄入后,本组合物将在胃中形成一种粘性基质,导致引起强烈的过饱的感觉,同时寡糖组分在胃肠道的下部提高钙的生物利用度。
刚性基质的形成需要低甲氧基化的果胶和/或藻朊酸盐。低甲氧基化的果胶和/或藻朊酸盐在和钙反应时形成一种足够刚性的基质以致产生过饱的感觉。本发明人发现在组合物中使用高水平的低甲氧基化的果胶和/或藻朊酸盐以治疗肥胖症或过重具有特殊的弊端。本发明人发现通过低甲氧基化的果胶和/或藻朊酸盐的凝胶化过程产生过饱感觉的组合物显著降低了钙的吸收和/或生物利用度。
本发现和在相关科学文献中的发现不相一致。举例来说:在近期的一篇综述性文章中,Greger等(Journal of Nutrition.1999;129:1434S-1435S)提到研究者已经发现在饮食中加入果胶不改变除镁之外的大多数矿物质的吸收。这个发现与先前由Bagheri等(1985)所发表的结果不同。Bagheri等研究了低甲氧基化的果胶对于猪中钙的吸收和滞留的影响。包含高甲氧基化的苹果果胶的饮食的钙的吸收是对照饮食的大约76%。当进食低甲氧基化的果胶时,钙的吸收降低到对照饮食组的1%。
钙在饮食中是最基本的。钙缺乏可以导致下列症状:肌肉痉挛,脆指甲,湿疹,关节痛,胆固醇水平升高,类风湿性关节炎,牙齿蛀烂,臂和/或小腿麻木。此外,它在可以用来预防或治疗过重和肥胖症的组合物中是非常重要的。有记载表明,被身体吸收时,钙有利于预防过重。因此,由于果胶和/或藻朊酸盐对于钙的生物利用度的影响,低甲氧基化果胶在用于降低体重和/或预防体重增加的组合物中使用有很多限制。
一种营养组合物的摄取,包括那些用来预防或治疗体重过重的,不应该成为一种不适当的负担。参加包含特定饮食(即拥有减少体重的欲望以及追求这种目标)的体重控制项目的人们因为不美味、不可口或饮食组分进食困难等原因经常过早的停止这个项目。发明者的经验认为所消耗的组合物应该是以液体的形式,这对参加体重控制项目的人来说比固体或半固体配方减少了负担。因此对于设计减少体重或者控制热量摄取的组合物而言,采用有限的粘度的液体形式是一个先决条件。然而,这提出了另外一个挑战,因为钙和低甲氧基化果胶在水环境中存在时形成粘性的物质。
发明者发现在液体可食用组合物中的低甲氧基化的果胶和/或藻朊酸盐对钙吸收的抑制作用能够通过与不消化的具有2到60之间聚合度的寡糖以及钙的共同服用而得到显著的降低。所述的液体可食用组合物使用了一种钙离子盐,它能够在中性pH附近提供有限量的游离钙离子,而在酸性pH时提供增加量的游离钙离子。因此本组合物是一种容易服用的、在吸收后能够产生过饱感觉的、并保证足够钙生物利用度的组合物。
不为理论所限,发明人认为本发明用的寡糖为肠内菌丛提供了一种容易代谢的基质。寡糖的摄食会导致肠道细菌数的增加,特别是双歧杆菌和/或乳酸菌和/或这些活性的提高,因而促进了果胶基质的降解。通过果胶基质在小肠和结肠上的促进性分解,钙的生物利用度将会通过果胶结合钙的加速释放而增加。而且果胶将会通过在胃和/或肠道内形成粘性基质产生期望的饱腹感诱导效应。此外,肠道细菌对于寡糖的发酵会产生乳酸盐和/或短链脂肪酸(SCFA),包括丁酸盐、丙酸盐和乙酸盐,导致结肠内pH降低,这使得矿物质溶解度升高,因而升高了离子化钙的浓度,加快了钙的被动扩散。此外,SCFA可以导致盲肠血流的增加,进而增加了矿物质的吸收。而且,寡糖能够通过盲肠壁的肥大促进肠钙的转运,因而增加了作为矿物质交换发生的场所的表面积,因此增加了钙吸收。
本组合物优选适用于一种预防和治疗肥胖症或过重的方法,特别适用于参加体重控制项目(例如,以降低体重为目的进食特定饮食)的对象,优选是人。
根据发明目的,本组合物对过重或肥胖的患者提供几种有利于健康的作用:
-饱腹感:本组合物在摄入后,提供了一种过饱的感觉,因而降低或消除了进一步摄取食物的欲望。饱腹感诱导效应至少部分是通过低甲氧基化的果胶和/或藻朊酸盐以及钙的作用导致胃中食糜的粘度升高所致。本组合物的一个重要的优点就在于所产生的饱胀感不会像许多特别是低热量食物那样很快消失。
-生物可利用的钙:过重的患者通过摄入生物可利用的钙而受益。然而,每日钙的摄取并不经常是足够的,如因为肥胖或过重的患者倾向于进食钙含量不足的食物,并改喝大量的软饮料。软饮料通常含有较高的磷酸盐,而磷酸盐能够进一步导致钙的生物利用度降低。储存在脂肪细胞中的钙(细胞内的钙)导致与肥胖症相关的代谢紊乱。低钙饮食增加了循环钙营养激素的水平,刺激了脂肪细胞钙的内流,进而导致脂肪生成的升高和脂解作用的降低。
-帮助降低或预防血液血清胆固醇水平的升高:过重或肥胖的患者通常受害于胆固醇水平升高和/或冠心病风险增加的痛苦。存在于组合物中的可溶性纤维,特别是优选的与β-葡聚糖结合的果胶,会通过结合回肠的胆酸降低血液中的血清胆固醇水平。可溶性纤维能够和胆酸相互作用,导致胆酸的粪便排泄增加,胆酸由胆固醇衍生而来,通常会被从回肠中重新吸收并被肝脏重新分泌为胆酸盐而有效地重新利用。根据胆酸盐在粪便中丢失的程度,肝脏必须使用胆固醇来代替损失的胆酸盐。此外,可溶性纤维的粘度和凝胶化性能对小肠中胆固醇的水解吸收以及胆酸的吸收具有重要的影响。
-增加大便的频率:已知寡糖能够促进肠的运动、增加大便的排出和频率。这对于受累于过重的患者非常有利,因为许多肥胖和过重的患者遭受便秘的痛苦。
-提供足够的水:发明者认为个体倾向于吃定量的食物,因为胃的膨胀引发了饱满迷走神经信号的传入。根据这一假设,进食高能量密度(ED)的食物会促使额外能量的摄入因为与能量相比的食物体积相对较小。Bell等的研究(Am J Clin Nutr 1998;67:412-20)证实能量密度影响食物的摄取。显然更多的能量是在高能量密度而不是中或低能量密度的情况下被摄入。食物中水含量的差异对于ED有很大的影响因为水含有零能量的。
-帮助控制血糖水平以及血液中胰岛素的水平,特别是饭后血液胰岛素的水平。这对于许多患者是很有利的,特别是那些受累于过重和/或II型糖尿病的患者。
具体实施方式
本发明的一个方面涉及一种液体可食用的组合物,其pH大于6,优选的pH是6-9,剪切速率为100s-1、20℃、约中性pH时,粘度低于600mPas,在37℃、pH低于5的粘度为前述粘度的125%,该组合物包含:
a.至少0.05重量%的甲氧基化的程度在2到50之间的果胶和/或藻朊酸盐;
b.每100ml至少5mg钙;以及
c.至少0.1重量%的不能消化的寡糖,其聚合度在2到60之间。
本发明的另一个方面涉及一种治疗或预防哺乳动物过重或肥胖症的方法,所述方法包含通过肠道给予哺乳动物有效量的前述组合物。本发明特别适用于治疗或预防人类的过重或肥胖症。
果胶
果胶通常是从柑橘或苹果的果肉的稀酸提取物中得到的碳水化合物。它们也存在于蔬菜和水果的细胞壁中。果胶也可以在如胡萝卜和甜菜根等的块根类农作物以及如马铃薯等块茎类农作物中发现。果胶的化学定义为聚半乳糖醛酸的部分甲基酯类,其分子量可以达到200,000。果胶是聚半乳糖醛酸的甲基酯类,在商业上可以从柑橘皮、苹果糊和糖用甜菜的废粕中提取得到。典型的果胶分子包含200到1000个以直链相接的半乳糖醛酸单元。
果胶可以分为两个主要的类别:高甲氧基化的果胶(下文中以HM果胶表示),其特征是甲氧基化程度高于50%;以及低甲氧基化果胶(下文中以LM果胶表示),其甲氧基化程度低于50%。在此所用到的“甲氧基化程度”(也称为DE或“酯化程度”),其目的是说明在聚半乳糖醛酸链中游离羧酸基团被酯化(例如被甲氧基化)的程度。
LM果胶进一步分为两个组:酰胺化的低甲氧基化和常规的低甲氧基化。这里所用的“酰胺化的程度”(DA)目的是表明聚半乳糖醛酸链中酯类基团通过与如溶液中氢氧化铵反应转化为酰胺基团的程度。
在本发明中所用到的LM果胶由低于50%的甲氧基化程度所表征,优选范围是5%到45%,进一步优选是10%到40%,更加优选是15%到35%。根据进一步优选的实施方案,LM果胶是被酰胺化的,其酰胺化程度优选为低于30%,进一步优选为低于25%,更优选为低于20%,酰胺化程度的下限优选是5%,更优选是10%。
本发明组合物中的LM果胶能够在正常人胃中pH,例如pH为3的情况下形成足够刚性的基质。因此根据本发明在每100ml(0.05重量%)包含至少0.05g LM果胶是必要的,优选为至少0.1g LM果胶,进一步优选为至少0.25g,更优选为至少0.5g,最优选为每100ml0.65g。但是LM果胶不能无限制的增加,因为在高浓度时组合物会产生不可接受的高粘性。组合物优选的LM果胶含量低于5重量%,更优选的低于1.5重量%,进一步更优选的低于1重量%。
藻朊酸盐
藻朊酸盐是包含β-(1→4)-连接D-甘露糖醛酸和α-(1→4)-连接L-半乳糖醛酸残基的线性非支链的聚合物,具有宽大的平均分子量范围(100-100000个残基)以适应其应用。藻朊酸盐的适宜来源包括海藻和细菌性藻朊酸盐。藻朊酸钠和藻朊酸钾被用作藻朊酸盐的最优选来源。
本组合物中的藻朊酸盐能够在正常人胃中pH例如pH为3的情况下形成足够刚性的基质。因此在本发明的组合物中每100ml至少包含0.05g藻朊酸盐(0.05重量%)是必要的,优选的在每100ml至少包含0.1g藻朊酸盐,更优选的是每100ml至少包含0.25g藻朊酸盐,进一步优选的是每100ml至少包含0.4g藻朊酸盐。然而,藻朊酸盐不能无限制的增加,因为组合物会产生不可接受的高粘性。本组合物优选的藻朊酸盐含量低于5重量%,更优选的低于2.5重量%,进一步更优选的低于1重量%。
钙盐
根据本发明本组合物优选含有一种钙盐,其在20℃的水中和组合物的pH下,比在37℃和pH低于5时的溶解度低很多。这种钙盐,当在组合物中存在的量超出其最大溶解范围时,将会由于在胃中pH的降低和/或温度的升高的影响下而溶解。因此组合物中钙离子的浓度会增加,进而自动刺激果胶和/或藻朊酸盐的凝胶化。
由于钙离子的凝胶化诱导效应,该离子在现有液体处方中的浓度(在接近中性pH)优选为相对较低。中性pH附近(溶解)钙离子的有限存在阻止了导致不可接受高粘度的凝胶基质的形成。因此,在一个优选的实施方案中,本组合物中钙盐的溶解度在20℃和pH为7时低于0.15,更优选为低于0.1克,进一步更优选为低于0.06克每100ml(去矿物质的)水。优选地,在pH低于5和37℃的温度时,钙盐提供了每100ml水大于0.2克的溶解钙。更优选地,在这种条件下,其提供了大于0.5g/100ml的溶解钙。这些钙盐从含有磷酸钙(例如磷酸钙、磷酸氢钙、磷酸二氢钙或三聚磷酸钙),碳酸钙,硫酸钙,氧化钙,柠檬酸钙(例如柠檬酸二氢钙或柠檬酸三钙),在pH为7的水中具有有限溶解度且在pH低于5的水中可溶的物质所包被的钙盐(下文中称作包被钙盐),及其混合物的组中优先选择。制备包被钙盐的实施例例和方法在WO0038829中给出,此处全文引用作为参考。更优选地,钙盐是从包含有包被钙盐,碳酸钙,磷酸钙及其混合物的组中选择。最优选的,主要的钙盐由碳酸钙提供。
为提供最佳的凝胶化性质,本发明组合物包含至少1.25mM钙(相当于每100ml 5mg Ca)。优选的钙浓度超过2.5mM(相当于每100ml10mg Ca),更优选的超过5mM,最优选的超过10mM。而且,组合物中钙离子浓度优选不超过1M,更优选的不超过500mM,进一步更优选的为不超过100mM。组合物中的钙浓度通过首先将钙完全溶解,其次测定钙离子的浓度而测得。当组合物在中性pH时大部分的钙将会以钙的络合物和/或不溶性钙盐的形式存在,因而不能与LM果胶形成粘性基质。在pH为1到5之间时,钙将主要以溶解形式和/或果胶钙络合物的形式存在。
为了降低含有LM果胶的组合物对肠道钙吸收的不利影响,组合物优先包含一定浓度的钙,其超过由LM果胶提供的负电荷浓度的0.5倍。
负电荷的浓度可以由下列公式计算:
MWp=果胶的分子量(g/mol)
MWp=半乳糖醛单元的分子量(g/mol)=194g/mol
MWe=侧链分子量(g/mol) =14g/mol
DE=酯化程度(%)
Cp=果胶浓度(g/l)
寡糖
本发明中所用到的词不消化的寡糖是指聚合度为超过2个单糖单元的糖类,更优选为超过3个,最优选为超过4个,它们不能或者只有部分在肠道中通过酸或人上部消化道(小肠和胃)的消化酶消化,但能被人肠道菌丛发酵。
寡糖的聚合度低于60个单糖单元,优选为低于40个,进一步优选为低于20个,最优选为低于10个。
单糖单元一词是指含有一个闭合的环结构的单元,优选的是己糖,如吡喃糖或呋喃糖形式。
寡糖优选至少含有90%,更优选含有至少95%的从含有甘露糖、阿拉伯糖、果糖、海藻糖、鼠李糖、半乳糖、β-D-吡喃半乳糖、核糖、葡萄糖、半乳糖醛酸、葡糖醛酸、木糖及其它们的衍生物的组中选出的单糖单元,以其所含单糖单元的总数目来计算。
适宜的寡糖优选由肠道菌丛发酵。本发明组合物中所用到的寡糖优选能够显著增加总盲肠和/或结肠的SCFA的含量。根据本发明优选的一个实施方案,当给予足够量时,与不含寡糖的组合物相比,寡糖能够增加至少20%总盲肠SCFA的含量,更优选为至少增加50%,进一步更优选为至少100%,最优选为至少150%。总盲肠SCFA的含量的增加可以通过由Campbell等所述的方法进行测定(The Journal ofNutrition Vol.127 No.1 January 1997,pp.130-136),此处全文引用作为参考。
优选的寡糖是从如下组中选择得到,包含:纤维二糖(4-O-β-D-吡喃葡糖基-D-葡萄糖),纤维糊精((4-O-β-D-吡喃葡萄糖)n-D-葡萄糖),B-环糊精(α-1-4-连接-D-葡萄糖的环形分子,α-环糊精-六聚物,β-环糊精-七聚物,γ-环糊精-八聚物),不消化的糊精,龙胆寡糖(gentioligosaccharides)(β-1-6连接葡萄糖残基,一些1-4连接体的混合物),葡糖寡糖(glucooligosaccharides)(α-D-葡萄糖的混合物),异麦芽糖寡糖(isomaltooligosaccharides)(线性α-1-6-连接D-葡萄糖残基和一些1-4连接体),异麦芽糖(6-O-α-D-吡喃葡糖基-D-葡萄糖),异麦芽三糖(isomaltriose)(6-O-α-D-吡喃葡糖基-(1-6)-α-D-吡喃葡糖基-D-葡萄糖),潘糖(6-O-α-D-吡喃葡糖基-(1-6)-α-D-吡喃葡糖基-(1-4)-D-葡萄糖),明串珠菌二糖(5-O-α-D-吡喃葡糖基-D-吡喃果糖苷),帕拉金糖(palatinose)或异麦芽酮糖(isomaltulose)(6-O-α-D-吡喃葡糖基-D-果糖),theanderose(O-α-D-吡喃葡糖基-(1-6)-O-α-D-吡喃葡糖基-(1-2)-β-D-吡喃果糖苷),D-琼脂糖,D-lyxo-己酮糖,乳糖蔗糖(O-β-D-吡喃葡糖基-(1,4)-O-α-D-吡喃葡糖基-(1-2)-β-D-吡喃果糖苷),α-半乳糖寡糖(galactooligosaccharides)包括棉子糖,水苏糖和其他的大豆寡糖(O-α-D-吡喃半乳糖基-(1,6)-α-D-吡喃葡糖基-β-D-吡喃果糖苷),β-半乳糖寡糖或反式半乳糖(transgalacto)-寡糖(β-D-吡喃葡糖基-(1,6)-[β-D-吡喃葡糖基]n-(1-4)α-D-葡萄糖),半乳糖苷果糖(4-O-β-D-吡喃半乳糖基-D-果糖),4’-半乳糖基乳糖(galatosyllactose)(O-D-吡喃半乳糖基-(1-4)-O-β-D-吡喃葡糖基-(1-4)-D-吡喃葡萄糖),合成的半乳寡糖(新半乳二糖、异半乳二糖、galsucrose、异乳糖I、II和III),果聚糖-左聚糖-型(β-D-(2→6)-呋喃果聚糖基)n-α-吡喃葡糖苷,果聚糖-菊糖-型(β-D-(2→1)-呋喃果糖基)nα-D-吡喃葡萄糖苷),1f-β-呋喃果糖基霉菌赤藓醛糖(fructofuranosylnystose)(β-D-((2→1)-呋喃果糖基)n-B-D-呋喃果糖苷),木寡糖(xylooligosaccharides)(B-D-((1→4)-木糖)n,lafinose,乳蔗糖,阿拉伯寡糖(arabinooligosaccharides)及其它们的混合物。
根据进一步的优选的实施方案,寡糖从如下组中进行选择,包括果聚糖,果寡糖(fructooligosaccharides),不消化的糊精,半乳寡糖(包括反式半乳寡糖),木寡糖,大豆寡糖,阿拉伯寡糖,葡寡糖,甘露寡糖,海藻寡糖,及其它们的类似物。
适宜的寡糖和它们生成的办法由Laere KJM深入的描述(Laere,KJM,Degradation of structurally different non-digestibleoligosaccharides by intestinal bacteria:glycosylhydrolases of Bi.Adolescentis.Ph.D-thesis,Wageningen Agricultural University,Wageningen,The Netherlands),此处全文引用作为参考。
本文中用到的词果聚糖可以分为两类,左聚糖和菊糖。左聚糖是具有由许多种细菌产生的不同程度的β-2,1-连接侧链的β-2,6-连接果糖。另一方面,菊糖和果寡糖是一组线性的葡糖基α(1→2)(果糖基)nβ(2→1)果糖聚合物,其聚合度(DP)的范围是从2到60。果寡糖或者是由菊糖的酶水解产生,或者是由蔗糖的反式果糖基化(transfructosylation)产生。如果寡糖的DP低于9,它们就被命名为果寡糖。主要的果寡糖有1-蔗果三糖(GF1),霉菌赤藓醛糖(GF2),果糖基霉菌赤藓醛糖(GF3),(GF=glycosylfructo-oligosaccharide,葡糖基果糖-寡糖)。具有较高DP的果聚糖组分被称为菊糖。举例来说菊糖是以商标RaftilineTM进行销售的(Orafti Active Food Ingredients,Belgium),果寡糖和寡蔗糖例如是以商标RaftiloseTM(Orafti ActiveFood Ingredients,Belgium)和NutraFloraTM(Golden TechnologiesCompany)进行销售。
记载表明NutraFlora可以增加总盲肠SCFA含量约260%,Raftilose可以增加总盲肠SCFA含量约244%。(Campbell等:The Journal ofNutrition Vol.127 No.1 January 1997,pp.130-136)。水解的菊糖可以从Rhone-Poulenc,Inc,Cranbury,N.J.得到。
半乳寡糖(包括反式半乳寡糖)一词是指不消化的糖类,其结构是侧链中半乳糖非常丰富并主要以葡萄糖为末端单元。两种半乳寡糖可以区分开。半乳寡糖可以由乳糖通过β-半乳糖苷酶的反式葡糖基作用或聚合的半乳聚糖经水解产生。β-半乳糖-寡糖可以由许多通过α-1,4-键连接到终端葡萄糖残基的β-1,6-连接半乳糖单元组成。另外一种类型的半乳寡糖是从大豆中分离得到的。这些α-半乳-寡糖(半乳糖基-蔗糖寡糖)包括棉子糖、水苏糖和毛蕊花糖,并且是由以α-1,6方式连接到蔗糖的葡萄糖母核部分的半乳糖残基组成。这些寡糖的生理作用看起来和β-连接的半乳糖寡聚体类似。半乳寡糖的组成可因链长度和单体单元之间连接类型的不同而变化。
举例来说反式半乳寡糖以商标Elix’orTM在销售(Borculo DomoIngredients,Netherlands)。半乳寡糖可以从Solabia,Pantin Cedex,France得到。
不消化的糊精可以从玉米淀粉经高温热解生成,它包含如天然淀粉中所存在的α(1→4)和α(1→6)糖苷键,还包含1→2和1→3连接以及左果糖。因为其结构特性,不消化糊精包含很成熟的并且被人消化酶部分水解的支链颗粒。
众多其它不消化寡糖的商业来源是容易得到并为本领域技术人员熟知。举例来说,反式半乳寡糖可以从Yakult Honsha Co.,Tokyo,Japan得到。大豆寡糖可以从由Ajinomoto U.S.A.Inc.,Teaneck,N.J.所予以配销的Calpis Corporation得到。
本发明组合物中优选包含寡糖的量超过0.1重量%,优选为超过0.2重量%,更优选为超过0.5重量%,进一步优选为超过0.9重量%。尽管服用相当多量的寡糖一般不会引起不良的副作用,但是本组合物中寡糖的量优选为低于20重量%,更优选为低于10重量%,进一步优选为低于5重量%。
根据本发明,认识到给予患者的LM果胶的量将会决定组合物中所需的寡糖的量是非常重要的。寡糖和果胶之间优选的重量比是超过0.25,更优选为在0.5和100之间,进一步优选为在0.75到50之间,最优选为在1和5之间。
水
水对于预防体重的增加和/或减轻肥胖症是非常重要的。本组合物含水的优选量是在50到99重量%之间,更优选的是在60到95重量%之间,进一步优选的是在75到90重量%之间。
补充组分
本发明的组合物适于用来代替一天中一次或多次的正餐或快餐。本组合物优选含有附加的营养成分,其对健康的饮食有进一步的帮助。
生物活性剂
维生素更优选加入到本发明的组合物中。所添加的维生素可从如下组中进行适当选择,包含维生素A、维生素E、维生素K、维生素C、维生素D、硫胺、核黄素、烟酸、维生素B6、叶酸、维生素B12、生物素、泛酸及它们的混合物。组合物优选含有至少三种从该组中选择的特定生物活性剂。根据优选的实施方案,组合物中至少应有维生素D以进一步帮助钙的吸收。肥胖或过重的患者经常受累于维生素D缺乏。
最容易和最天然的获取维生素D的方法是接受太阳光的照射,这样使得机体制造自身的维生素D。但是试图减肥的人们自尊心往往很低,因此不愿意暴露于太阳光下,例如通过日光浴。而且,维生素D的通常来源,像牛奶等奶制品,在过重患者的饮食中经常被苏达饮料所代替。本发明组合物中的生物活性剂的含量范围是从特定生物剂每日推荐摄取(RDA)的5%到RDA的250%。RDA已经由美国食品药品监督管理局公布。
矿物质
本组合物中可以添加矿物质。所添加的矿物质可以从如下组中进行适当选择,包含铁、锌、铜、铬、碘、硒、镁、锰、钼、胆碱、钾、磷酸盐、氯化物及其混合物,优选的至少含有三种从该组选择的特定矿物质。
根据本发明组合物中适宜的矿物质的含量从特定矿物质的每日推荐摄取(RDA)的5%到250%,优选为RDA的10到50%之间。RDA已经由美国食品药品监督管理局公布。
纤维
本组合物除了LM果胶或聚合度在2到60之间的不消化寡糖之外还适当含有一或几种其他的纤维。其他的纤维可以从可溶和不溶的纤维中进行选择。这些纤维可以通过降低胃排空的速率促进LM果胶的饱胀感的作用,和/或在肠道中提供缓慢的蔗糖释放,有助于延长饱胀感。而且,纤维可以阻止或降低便秘,并且有助于本发明组合物降低血液血清胆固醇水平的作用。
当其他纤维是可溶性纤维时,本发明的可溶性纤维优选从如下组中选择,包含高甲氧基化果胶、脱乙酰壳多糖、β-葡聚糖、从车前草外皮(下文中称作车前草)得到的可溶性纤维、黄原胶、瓜儿豆胶、刺槐豆胶、阿拉伯胶、大豆纤维及其混合物。更优选的是从包含车前草、果胶、β-葡聚糖及其混合物的组中选择。β-葡聚糖优选从全燕麦获得,更优选是全燕麦可溶性纤维组分的一部分。
其他纤维在组合物中的优选含量是每100ml从0.1g到10g纤维,更优选的是在0.2到5克之间,优选每100ml包括0.05到2克β-葡聚糖。
蛋白质
蛋白质对于人体的营养是必需的。因此本发明的组合物优选包含每100ml组合物1到20克蛋白质,更优选为2到10克。
蛋白质优选从蔬菜原料得到,更优选的每100ml包含1克大豆蛋白,其中大豆蛋白优选从大豆蛋白浓缩物和分离大豆蛋白制品中选择。
可消化的糖类
本组合物可含有可消化的糖类。当该组合物设计用来代替一或多餐时,包含可消化糖类是可取的。
可消化糖类一词包括可消化的多糖和单糖,即可以被肠道酸和/或肠道酶消化和/或被肠道细胞吸收的糖类。举例来说,可消化的糖类可以是淀粉、麦芽糖糊精或单糖。优选的该组合物包含0.2到5重量%的单糖,更优选的包含1到3重量%。根据进一步优选的实施方案,单糖主要有果糖组成。
如本处方中淀粉和麦芽糖糊精那样的可消化的糖类的加入可进一步有助于饱胀的感觉。当组合物是以即饮(ready-to-drink)的形式存在时,组合物优选含有低(非麦芽糖糊精)淀粉组分因为加入可观量的淀粉将不可避免的导致在热处理过程(如灭菌)中粘度的增加。因此,组合物优选含有每100ml低于1克淀粉,更优选低于0.5克,进一步优选低于0.2克。可消化的麦芽糖糊精(DE在5到30之间,优选为20左右)适宜加入到本组合物中以提供如麦芽糖糊精的饱胀的作用,与其它淀粉和淀粉衍生物不同,其适用于热处理的液体。优选地,本组合物的制剂含有每100ml的0.5到20g麦芽糖糊精,进一步优选为每100ml2到10克麦芽糖糊精。
脂肪
当该组合物的目的是替代一顿或多顿正餐时,加入类脂或脂肪是可取的。类脂优选地是从植物资源获得,例如菜籽油或橄榄油,它们通常含有相对较高的单不饱和和/或聚不饱和脂肪酸。优选的本产品中包含至少大约10重量%的类脂为聚不饱和脂肪酸。本组合物中类脂的含量优选为0.2到10重量%,更优选为0.5到5重量%之间。
果胶的液体组分,钙,寡糖和水
对于希望减少热量摄取的患者而言,本组合物可几乎不含高热量组分。因此,以液体组分总重量计算组合物,优选含有低于5重量%的可消化的糖类和脂肪,更优选的是低于2重量%,进一步优选的是低于1重量%。在进一步的实施方案中,本发明提供了一种液体可食用组合物,其pH大于6,粘度在剪切速率为100s-1和20℃时低于600mPas,在pH低于5和37℃时为前述粘度的125%,其中组合物的至少95重量%由果胶、钙盐、寡糖和水组成。在一个优选的实施方案中,本组合物至少95重量%由至少0.05重量%的甲氧基化程度为2到50的果胶和/或藻朊酸盐;每100ml至少5mg钙;至少0.1重量%聚合度在2到60的不消化寡糖;以及水。
根据进一步优选的实施方案,上述组合物总重量的至少98重量%是由果胶、寡糖、钙盐和水组成,更优选至少99重量%。前述组合物可包含矫味剂如调味剂、低热量甜味剂、着色剂和/或稳定剂。此外组合物还包含其它的营养组分,其可以例如原料形式存在,并为组合物处方所必需,例如,许多果胶原料包含少量的蔗糖。由限定量的成分组成的上述组合物,优选含有低于大约50kcal/100ml的营养值,更优选低于大约25kcal/100ml,进一步更优选低于10kcal/100ml。
应用
通过例如往含有果胶和/或藻朊酸盐、钙和寡糖的粉末中,简单的加入预定量的水和/或牛奶,消费者可恰当地制备本液体可食用组合物。因此,本发明的一个方面是提供一种混合物来制作可复水的的形式的液体可食用的组合物,包含a)一种从包含低甲氧基化果胶、藻朊酸盐及其混合物的组中选择的多糖;b)钙;以及c)寡糖,其中一份组合物可以用预先量好的适宜的溶剂溶解以产生本液体可食用组合物。适宜的溶剂优选pH大于6,适宜从包含水、牛奶及其混合物的组中选择。优选的用于制备本液体可食用组合物的混合物是粉末的形式。
本发明也提供了用于制备本液体可食用组合物的工艺过程,所述过程包含混合前述混合物与优选的从包含水、牛奶及其混合物的组中选择的溶剂。文中用到的“可复水的形式”一词是指一种需要添加适宜溶剂(优选水)以获得本发明可食用液体组合物的制剂。优选的可复水的制剂是一种可复水的粉末。
本组合物也可以是即饮的形式,它不需要进一步加工就可以饮用,即在摄入前不需要加入水。
根据优选的实施方案,本组合物可以以一种包装好的饮品的形式供应,其含有至少25ml,更优选至少50ml,进一步优选至少100ml组合物。优选的包装饮料的含量不超过2000ml,更优选低于1000ml,进一步优选低于500ml,最优选低于400ml。当本组合物以粉末形式供应时,优选附带一本说明书以便将粉末与预定体积的水重组,例如通过摇晃或搅拌,以得到本发明的组合物。优选的该组合物在重新混匀后60分钟内被饮用。
该液体组合物在饮用之前优选经过热处理,优选通过巴氏消毒法、灭菌或超级巴氏消毒法。而且本组合物优选含有一种或多种调味品和/或着色剂。本组合物优选用于替代一次或多次正餐,优选的一次或多次选自早餐、中餐或正餐中的一餐。本组合物优选每天饮用多于一次。
本文中用到剂量一词时,是指在一个相当短的时间范围内本组合物的总的饮用量。当提到服用特定量时,所述的量优选在一个小时内服用,更优选为30分钟内,进一步优选为10分钟内。
粘度
本液体组合物的剪切速率为100s-1及20℃时,粘度低于600mPas,在pH低于5和37℃时为前述粘度的125%。
液体可食用的组合物优选具有限定的粘度。因此,根据一个优选的实施方案本组合物的粘度在当剪切速率为100s-1和20℃时,低于250mPas,更优选低于100mPas,最优选低于50mPas。
优选地,在pH为3和37℃时,组合物的粘度在中性pH时至少是前述粘度的150%,更优选大于200%,进一步更优选大于400%。优选地,在pH为3和37℃时,组合物的粘度超过250mPas,更优选超过300mPas,最优选超过400mPas。
本文中当用到粘度一词时,是指用如下方法测定的物理常数:
粘度可以用Carri-Med CSL流变仪来测定。使用的转子形状是圆锥形(6cm 2deg丙烯酸圆锥体),在板和转子的间距被设定为55μm。使用的线性的持续上升的剪切速率是在20秒内从0到150s-1。流变仪的自动调温器设定在适当的温度(例如20℃或37℃)。
为了测定酸性pH(pH 3)的条件下的粘度,首先在本组合物中均匀的混入(逐滴加入并轻轻搅拌大约20秒以防止凝胶的破坏)足够量的1M HCL以调节组合物的pH到pH 3。其后组合物在20℃放置大约10分钟,然后所得的组合物根据上述方法用来测定在pH 3时的粘度。
为降低本组合物的粘度(在接近中性pH),可适当加入从多元醇,如山梨糖醇、麦芽糖醇或赤藓醇中选择的成分。这些成分具有的优点是在低pH时它们几乎不能影响本组合物的粘度。优选的这些降低粘度的成分加入的量是0.5到50重量%。本组合物中多元醇应用的适当例子在WO0038829中给出,在此全文引用作为参考。
根据本发明的另一个实施方案本组合物还可以包含一种阴离子,它可以在pH 7时和钙形成络合物或不溶性的盐。代表性的及优选的,该阴离子由pH 7时可溶性的盐提供。该盐可以是柠檬酸或磷酸的钾或钠盐。这种盐优选的使用量是在0.2到10重量%之间。
含有果胶和钙饮料的一个问题是这种产品的有限的贮藏寿命。随着时间的延长,含有果胶的产品粘度会增加,导致形成一种几乎不能饮用的剂型,或者甚至更坏,组合物变成固体或如凝胶般坚固。因此先前本领域一般不把钙盐和LM果胶在一个在市场上以液体形式出售的组合物内组合。
本组合物特定的成分组合保证了良好的贮藏寿命,本组合物优选以这种方式配方,液体可食用的组合物的粘度在贮存60天(20℃)后低于开始粘度的300%,更优选低于200%,进一步优选低于150%。开始粘度在组合物制造后2天时测定。
治疗方法
本组合物优选用来治疗或预防一种疾病(disease)或病症(disorder)。在一个优选的实施方案中,本组合物用于预防或治疗哺乳动物的过重的方法。本发明所用的过重一词是指在期望的体重和/或期望的肥胖组织质量之上的体重和/或脂肪组织质量。本方法可适用于减少脂肪组织质量或预防脂肪组织质量的增加,作为一种方法用来增加瘦的身体质量与脂肪组织质量的比例和/或肌肉质量与脂肪组织质量之间的比例。
本方法可以用作在医学意义上的治疗或预防过重和/或美容治疗或预防过重。优选地本方法用于治疗或预防人体的过重。
进一步发现本组合物适于用来诱导饱胀感。因此本组合物可以优先的用作一种激发饱胀感的方法,特别是哺乳动物餐后的饱胀感。本组合物可以用来为那些因为食物消耗受到限制而缺乏饱胀感的病人提供饱胀的感觉。例如那些食用固体食物有困难或被要求进食液体食物的病人,特别是住院的病人和老人。特别的,对于那些被动地(通过口部管饲)获取大部分或全部每日的所需营养以保持蛋白合成及避免营养不良的病人可以优先使用本组合物。因此本组合物包含口部管饲本组合物的方法。
进一步发现本组合物可以用来控制血液的胰岛素水平。因此,本组合物可以便利的用于一种降低血液的胰岛素水平方法,特别是餐后的胰岛素水平。此外本组合物可以用来降低(餐后)胰岛素峰或(餐后)胰岛素的分泌。本发明组合物可优先用于维持健康的胰岛素水平。本组合物因此便利的用作一种方法来治疗和/或预防II型糖尿病,所述方法包含给予患者有效剂量的本组合物。
在上述方法中,本组合物优选用于至少部分代替一顿或多顿正餐。
实施例
实施例1
制备一种包含如下成分的组合物:
●0.55克31%甲氧基化的,17%酰胺化的苹果果胶
●154mg碳酸钙
●0.4g柠檬酸三钾
●1克Fibersol 2TM(Matsutani Chemical industry Co.,Japan)
●加水至100ml(用10%KOH溶液调pH至7)
在pH 7、20℃、剪切速率为100s-1时,组合物的粘度是32mPas。在pH 3、37℃时、形成刚性凝胶(粘度>>1000mPas)。
实施例2
制备一种包含如下成分的组合物:
●0.62克31%甲氧基化的,17%酰胺化的苹果果胶
●154mg碳酸钙
●0.42g柠檬酸三钾
●1克Fibersol 2TM(Matsutani Chemical industry Co.,Japan)
●4.55克分离大豆蛋白制品
●0.86克燕麦麸皮
●3.18克麦芽糖糊精19DE
●1.54克果糖
●0.31克菜籽油
●0.31克橄榄油
●80mg维生素混合物
●60mg矿物质和微量元素混合物
●加水至100ml(用10%KOH溶液调pH至7)
该组合物均质化并灭菌。在pH 7、20℃、剪切速率为100s-1时,组合物的粘度是27mPas。在pH 3、37℃、剪切速率为100s-1时,组合物的粘度是150mPas。
实施例3
一种包含如下成分的组合物:
●0.1克31%甲氧基化的,17%酰胺化的苹果果胶
●50mg碳酸钙
●0.4g柠檬酸三钾
●1克Fibersol 2TM(Matsutani Chemical industry Co.,Japan)
●0.5克蔗糖
●5克全脂奶粉
●11克燕麦麸皮
●加水至100ml(用10%KOH溶液调pH至7)
在pH 7、剪切速率为100s-1时,组合物的粘度是48mPas。在pH3,形成刚性凝胶(粘度>>1000mPas)。
实施例4
一个使用安慰剂作为对照的,双盲的,随机交叉的研究用来评价摄入该组合物对餐后血糖和胰岛素以及食欲感觉的影响。
研究群体
在Wageningen和周围地区招募的志愿者。在大学和学生公寓的几个地方张贴海报并且在当地的报纸上登载广告。参加研究的加入标准是:身体质量系数(BMI)18.5-27kg/m2,空腹时葡萄糖水平<6.0mmol/L,不吸烟,年龄18-55岁。排除标准是:影响胃肠道的药物的使用(如抗生素,泻药),医师确定的I或II型糖尿病,上一年体重变化>10%,不正常的饮食习惯(如特定饮食,严格的素食主义者),怀孕或想要怀孕的,哺乳期的,胃或肠手术的,精神病患者。
在筛选空腹期间葡萄糖水平时,测定了体重和身高。体重测定至最近似的0.1kg,测定对象不穿鞋,并穿着轻便衣服。身高测定的是cm且测试对象不穿鞋。BMI由体重和身高进行计算:体重(kg)/(身高(m))2。根据这些结果可以确定测定对象可否参与研究。
招募了33个健康的不吸烟的对象(7男21女),年龄在25±9年,BMI 21.9±2.4kg/m2,空腹葡萄糖水平是4.4±0.5mmol/l。研究由研究员解释。所有的对象在参与研究之前,都签署了知情同意的表格。
研究设计
参加者随机分为两组,每组以不同的顺序接受CarboMix和ControlMix(CarboMix和ControlMix的成分在下面列出,参见试验产品)。餐后血糖反应和食欲在两种情况下进行测量,一个是在摄入CarboMix后,另一个是在摄入ControlMix后。测量至少间隔4天。在每个研究日前的晚上,测定对象食用一餐标准的意大利面。不允许做任何体育运动。
在每个测试日,经过12小时的整夜禁食,一个特氟纶的导管插入受试者胳膊前臂静脉取得禁食血样。保持导管以便反复取样。同时,受试者被要求评定他们的食欲感觉。随后,受试者在10分钟内进食CarboMix或ControlMix。餐后的血液样品在第一次吞咽下混合物后的10、20、20、40、50、60、75、90、120、150和180分钟取得以测定血糖和胰岛素的水平。在每个血液样品后,1ml肝素(=200单位)加入到特氟纶导管中以阻止导管中血液的凝结。因此开始时先取大约2-3ml以除去管中的肝素,然后取两个4.5ml的血液样品。这样导致每天测定的总血样为大约132-144ml。在取每个血样时,受试者被要求填写调查表以评定他们的食欲感觉。至少4天后,使用另一混合物,该程序重复进行。错过两次测量(CarboMix或ControlMix)之一的受试者将被排除在研究之外。
测试的产品
CarboMix:糖混合物由50克合用的糖类和14.3克纤维(混合物A溶解在281ml的水中)组成。ControlMix:糖混合物由合用的糖类组成,没有纤维(混合物B溶解在292ml的水中)。两种糖混合物最终的体积为325ml。混合物A和B的成分如表1所示:
表1
*1由41.5克Glucidex 19(Roquette)提供
*2由41.5克Glucidex 39(Roquette)提供
**由4.45克Snow White Oat Fibre 500(Canadian Harvest)提供
***由4.54克Genu-pectin LM-104 AS(Orffa-Hercules)提供
******Orange 610582H(Givaudan)
*******Sunset yellow(Eurocert)
生化测定
测定了血浆葡萄糖和胰岛素的含量。对葡萄糖的分析,样品收集在含草酸钾的试管中。离心后,血浆样品储存在-20℃,葡萄糖根据标准的实验室方法进行测定。对于胰岛素分析,样品收集在凝固管中并在凝固后进行离心,血浆样品储存在-20℃,胰岛素根据放射免疫法进行。
食欲调查表
食欲的分值以视觉模拟尺度法(VAS评分法)通过在每条线上间隔100mm刻线的方式。“一点也不”一词放置在左边,“非常想”一词放置在右边,以对每个标记进行打分。标记放置在线上面。标记“吃饭的食欲”是指吃一整顿饭的食欲,不管是热餐还是三明治餐。“饱胀感(饱)”是指饱或吃得太多的感觉。标记“无力,因饥饿虚弱”是指有明显身体表征的想吃饭的迫切要求(de Graaf C et al,Short-term effects of different amounts of protein,fats,and carbohydrateson satiety.Am J Clin Nutr 1992;55:33-8)。
统计分析
对于治疗效果,遗留物的影响得到测定。对于没有遗留影响的变量,应用统计学试验测定治疗效果。所有的分析都用到了非参数检验。对于葡萄糖、胰岛素和来自食欲调查表的VAS分数中的曲线下增加的面积,峰高和达峰时间,使用了双样品Mann-Whitney U检验。当p<0.05时,假定有统计学差异。
结果
结果的表示是平均值±SEM
血糖
血糖曲线在摄入CarboMix后比摄入ControlMix要低。90分钟后血糖曲线下增加的面积,CarboMix要低于ControlMix(表2)。
表290分钟后血糖曲线下增加的面积(mmol*分钟/l)
胰岛素
胰岛素曲线在摄入CarboMix后比摄入ControlMix要低。90分钟后胰岛素曲线下增加的面积,CarboMix要显著低于ControlMix(表3)。CarboMix比ControlMix,其胰岛素的峰值更低(表4),达峰时间显著短(表5)。
表3 90分钟后胰岛素曲线下增加的面积(mU*分钟/l)
表4 胰岛素的峰值(mU*分钟/l)
表5 胰岛素达峰时间(分钟)
食欲
在饮用完饮料后从10到75分钟,对于问题“渴望进食”的分值,CarboMix低于ControlMix。在20和30分钟后,这些值有显著性的差异(表6)。
表6 20和30分钟后对于问题“渴望进食”的分值
在喝第一口饮料后从10到80分钟,对于问题“饱胀感觉”的分值,CarboMix高于ControlMix。这些值在50分钟后有显著性的差异(表7)。
表7 50分钟后对于问题“饱胀感觉”的分值
在引用完饮料后的从10到70分钟,对于问题“因饥饿而虚弱”的分值,CarboMix高于ControlMix。在20和30分钟后,这些值有显著性的差异(表8)。
表8 20和30分钟后对于问题“因饥饿而虚弱”的分值
实施例5:在发酵过程中钙的利用度
MacFarlane培养基的制备
蛋白胨的水缓冲液 3.0g/l
酵母提取物 2.5g/l
胰蛋白胨 3.0g/l
L-半胱氨酸-HCL 0.4g/l
胆盐 0.05g/l
K2HPO4·3H2O 2.6g/l
NaHCO3 0.2g/l
NaCl 4.5g/l
MgSO4·7H2O 0.5g/l
CaCl2 0.228g/l
FeSO4·7H2O 0.005g/l
用2M HCl调整pH至6.3±0.1,然后培养基进行灭菌。
粪便的悬浮液的制备
在无氧条件下,人的粪便悬浮在MacFarlane培养基中,其重量比是粪便:MacFarlane培养基为1∶5。悬浮液随后过筛以除去固体组分。
发酵
15ml的粪便悬浮液与干的包含有果胶或钙;或果胶、钙和寡糖(见表9)的混合物混合,在37℃,无氧条件下温育24小时。温育后,固体经离心从悬浮物中去除,pH和钙的浓度用钙电极(型号720A,ThermoOrion,Beverly,USA)测定。结果如表9所示:
表9
*Fibersol-(Matsutani)
**RaftiloseTM(Orafti Active Food Ingredients)
***Genu-pectin LM-104 AS(Orffa-Hercules)
Claims (31)
1.一种液态可食用的组合物,其pH大于6,粘度在剪切速率为100s-1和20℃时低于600mPas,以及粘度在温度为37℃和pH低于5时至少为前述粘度的125%,该组合物包含:
a.至少0.05重量%的含有甲氧基化程度在2%到50%之间的果胶和/或藻朊酸盐;
b.每100ml至少5mg钙;以及
c.至少0.1重量%的聚合度在2和60之间的不消化寡糖。
2.如权利要求1所述的组合物,其包含在0.4到5重量%之间的甲氧基化程度在5%到45%之间的果胶。
3.如权利要求1或2的组合物,其中钙由在pH 7和20℃时溶解度低于每100ml去矿物质水0.10克的钙盐或氧化钙提供。
4.如权利要求1或2的组合物,其包含0.1到10重量%的聚合度在2到40之间的不消化寡糖。
5.如权利要求1或2的组合物,其每100ml包含从0.1到10克的钙。
6.如权利要求1或2的组合物,其中不消化寡糖选自以下组中:果聚糖、不消化糊精、半乳寡糖、木寡糖、大豆寡糖、阿拉伯寡糖及其混合物。
7.如权利要求6的组合物,其中所述果聚糖是果寡糖。
8.如权利要求3的组合物,其中钙盐选自以下组中:磷酸钙、碳酸钙、硫酸钙、柠檬酸钙、在pH为7的水中具有有限溶解度且在pH低于5的水中可溶的物质所包被的钙盐及其混合物。
9.如权利要求1或2的组合物,其包含50到98重量%的水。
10.如权利要求1或2的组合物,其每100ml包含1到25克蛋白质。
11.如权利要求1或2的组合物,其包含0.2到10重量%的脂肪。
12.一种包装的饮品,包含50到100ml的如权利要求1-11任一项的组合物。
13.权利要求1到11之一所述的组合物在制造用于预防或治疗哺乳动物过重的组合物中的应用。
14.权利要求1到11之一所述的组合物在制造用于预防或治疗哺乳动物的II型糖尿病的组合物中的应用。
15.权利要求1到11之一所述的组合物在制造用于激发哺乳动物的饱胀感的组合物中的应用。
16.权利要求15的应用,其中所述组合物用于激发哺乳动物的餐后的饱胀感。
17.权利要求1到11之一所述的组合物在制造用于降低或预防血液血清胆固醇的升高的组合物中的应用。
18.权利要求1到11之一所述的组合物在制造用于降低血液胰岛素水平、降低胰岛素的峰值和/或降低胰岛素的分泌的组合物中的应用。
19.如权利要求13-18之一的所述应用,其中所述组合物包含的不消化寡糖选自以下组中:果聚糖、不消化糊精、半乳寡糖、木寡糖、大豆寡糖、阿拉伯寡糖及其混合物。
20.如权利要求13-18之一的应用,其中所述组合物包含的不消化寡糖是一种合成的半乳寡糖。
21.如权利要求13-18之一所述的应用,其中的组合物包含的不消化寡糖选自1-蔗果三糖、霉菌赤藓醛糖和1f-β-呋喃果糖基霉菌赤藓醛糖。
22.如权利要求13-18之一所述的应用,其中的组合物包含的不消化寡糖是菊糖。
23.如权利要求1到11之一所述的组合物在制备在降低餐后血糖水平的方法中使用的组合物中的应用,其中所述用于降低餐后血糖水平的方法的组合物包含的不消化寡糖选自以下组中:果聚糖、不消化糊精、半乳寡糖、木寡糖、大豆寡糖、阿拉伯寡糖及其混合物。
24.如权利要求23的应用,其中所述组合物包含的不消化寡糖是一种合成的半乳寡糖。
25.如权利要求23的应用,其中的组合物包含的不消化寡糖选自1-蔗果三糖、霉菌赤藓醛糖和1f-β-呋喃果糖基霉菌赤藓醛糖。
26.如权利要求23的应用,其中的组合物包含的不消化寡糖是菊糖。
27.如权利要求17所述的应用,其中所述组合物配制为用于对哺乳动物进行肠内给予的形式。
28.如权利要求18所述的应用,其中所述组合物配制为用于对哺乳动物进行肠内给予的形式。
29.如权利要求19所述的应用,其中所述组合物配制为用于对哺乳动物进行肠内给予的形式。
30.如权利要求20所述的应用,其中所述组合物配制为用于对哺乳动物进行肠内给予的形式。
31.一种用来制作液态可食用的组合物的混合物,其可复水的形式包含
a.一种选自甲氧基化低于50%的果胶、藻朊酸盐及其混合物中的多糖;
b.钙;以及
c.聚合度为2-60的不消化寡糖,其中所述混合物为能够用选自包含水、牛奶及其混合物的组中预先量好的适宜的溶剂溶解以生成一种液态可食用的如权利要求1-11之一所述的组合物的形式的混合物。
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US10/022,372 US6884445B2 (en) | 2001-12-20 | 2001-12-20 | Matrix-forming composition containing pectin |
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EP20020079289 EP1410722A1 (en) | 2002-10-16 | 2002-10-16 | Weight loss kit and method for losing weight |
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US10/279,968 US6989166B2 (en) | 2001-12-20 | 2002-10-25 | Soft drink replacer |
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PCT/NL2002/000856 WO2003053165A1 (en) | 2001-12-20 | 2002-12-20 | Matrix-forming composition containing pectin |
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