CN103442595A - 含有二胺氧化酶的功能性食品及其用途 - Google Patents
含有二胺氧化酶的功能性食品及其用途 Download PDFInfo
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Abstract
本发明涉及含DAO的功能性食品及其用于预防或治疗与血液中高水平的组胺相关的疾病或病理状况的用途,特别用于治疗或预防偏头痛、慢性疲劳、纤维肌痛、脊椎炎和由肌肉挛缩引起的疼痛的用途。
Description
发明领域
本发明涉及含有二胺氧化酶(DAO)的功能性食品,所述功能性食品用于治疗或预防与血液中高组胺水平相关的疾病或病理状况,特别用于治疗或预防偏头痛、慢性疲劳、纤维肌痛、脊椎炎和由肌肉挛缩引起的疼痛。
背景技术
组胺[2(4-咪唑基)-乙胺]为一种在很多生物学过程——包括发炎、胃酸分泌、神经调节和免疫功能调节——中的重要介质。由于其有效的药理学活性,因此甚至在极低浓度下,也需要仔细地调节组胺的合成、转运、存储、释放和降解,从而防止不需要的反应。循环系统中高浓度的游离组胺引发不希望的效应,例如头痛、鼻塞或流涕、呼吸道阻塞、心跳过速、胃肠功能紊乱、眼睑肿胀、皮疹、低血压、支气管痉挛等。
组胺由人体产生,并且以非活性形式存储在肥大细胞和嗜碱性粒细胞的异染颗粒中,组胺可在其中立即释放。最高浓度的组胺在肺中测得。释放后,组胺——还常常通过与细胞因子相互作用——变成大量生理学和病理学过程的非常有效的介质。
组胺也可以从体外进入体内,由于其通过在食品加工过程中的微生物作用而产生,因此,组胺在许多食品类和发酵饮料(例如奶酪、葡萄酒、罐头鱼和酸菜)中大量存在。
组胺在由组氨酸脱羧酶(HDC)催化的反应中通过L-组氨酸氨基酸的脱羧作用形成。在哺乳动物中组胺失活的主要路径是由组胺-N-甲基转移酶(NMT)催化的咪唑环的甲基化以获得N-甲基组胺,以及由二胺氧化酶(DAO)催化的伯氨基基团的氧化脱氨基作用以获得咪唑乙醛。
两种降解方式对有机体是必不可少的:DAO消除通过肠道内食品吸收的组胺,且NMT控制神经系统内组胺能信号的传递。
DAO的主要功能是防止通过食品摄取的组胺从肠到达血液循环。
除了组胺,DAO也可降解其他生物胺,例如腐胺、亚精胺和尸胺(cadaverine)。DAO的分子量为约182kDa并且其碳水化合物比例为11%。DAO属于含铜的胺氧化酶类,其催化伯胺的氧化脱氨基作用以获得醛、氨和过氧化氢。DAO利用分子氧以将组胺氧化脱氨基成咪唑乙醛、氨和过氧化氢。
DAO主要发现于小肠、肝、肾和血液白细胞中。妊娠妇女血液中的DAO水平比非妊娠妇女高约500至1000倍,这是因为DAO还在胎盘中形成。组胺在人体内连续产生,并且经肠分泌,随着其通过肠黏膜时通过存在于此的DAO而降解。
DAO是可由多种物质(例如其他生物胺、醇及其乙醛降解产物)以及由多种药物抑制的敏感性酶。
DAO缺乏已被关联为一种可能的偏头痛诱发因素——妇女中盛行的病况。由于缺乏DAO,身体中过量的组胺增加了偏头痛的风险。
EP132674公开了一种利用胺氧化酶——特别是DAO(由黑曲霉(Aspergillus niger)生物体获得)——在分子氧的存在下将具有高含量游离胺的食品(例如巧克力、奶酪——特别是成熟奶酪(maturedcheese)——香肠、葡萄酒和酵母提取物)中的游离胺酶法分离的方法。在某些食品中这些游离胺的存在被认为引发偏头痛。
美国专利4725540公开了一种以下的方法:由产生DAO的微生物(例如克鲁斯假丝酵母(Candida crusei))或产生乳酸的细菌在营养培养基中制备DAO,从而使制得的DAO能够将组胺降解为中性至约4的pH。
在60年代引进了具有健康益处的新型食品的可用性。从那时起,市场上便出现了设计用于无麸质、低钠、低卡路里膳食等的新型食品。该食品还被称为“功能性食品”,包括任何天然或加工形式的食品,该食品除了其营养组分外还包括促进人体健康、体能以及精神状态的其他组分。其作为功能性的描述涉及“功能特性”的食品学概念,即,已经显现出对一个或多个特定身体机能具有有利效果并与其营养价值无关的某种食品的特性。因此,该类食品与健康和幸福相关,并且有助于降低给定疾病的风险。
美国是更坚定确立意欲用于预防人群中疾病的功能性食品的国家之一,所述功能性食品为例如意欲用于中年妇女补钙以预防骨质疏松症的谷物棒、或用于降低乳腺癌风险的大豆蛋白、或用于使心脏更加健康的叶酸、或含有蛋白质、锌和抗氧化剂的能量饼干。
在欧洲,各种具有不同治疗目的的功能性食品也是已知的,例如:
·富含ω-3必需脂肪酸的蛋,其有助于降低心脏病的风险。
·用益生菌培养发酵以帮助消化的乳和酸奶。
·含叶酸的谷物,用于帮助降低患有先天性脊柱裂的儿童的数量。
·含植物甾醇的人造黄油,其降低胆固醇并降低心脏病的风险。
专利申请EP865737公开了富含可溶性和不可溶性钙盐的平衡混合物的乳制品基食品。
专利申请WO9631130公开了含有钙和维生素D源的饮料浓缩物。
专利申请WO9207475公开了油乳形式的含钙源的沙拉酱产品。
美国申请4851243公开了稳定悬浮液形式的富含钙的乳制品。
然而,用于帮助预防或治疗与血液中高组胺水平相关的疾病和状况的含DAO的功能性食品尚不被知晓。
定义
“功能性食品”(在文献中常常缩写为FF)是不仅用于其营养特性还用于实现特定功能例如改善健康并且降低疾病风险而制备的食品。为此,加入生物活性组分,例如矿物质、维生素、脂肪酸、膳食纤维和抗氧化剂等。这种加入外源性营养素的操作还被称为营养强化(fortification)。该类食品是在食品研究中是具有充足可能性的食品科学的新兴领域。在科学文献以及食品营销中列出的一些成果是改善胃肠功、贡献氧化还原和抗氧化体系,以及大量营养素代谢的改变。该类食品涵盖了可以从仅谷物及其衍生物至所有种类乳制品延伸的宽谱的可能性。
“非植物来源”意指不是从植物中得到而且从动物有机体或其他非植物有机体中得到的所有DAO。因此,该定义涵盖了所有从活的生物体分离的DAO。
“植物来源”意指所有从植物有机体获得的DAO。
“生物技术来源”意指所有在细胞培养中或在任何类别的用于DAO的DNA分离的非植物有机体中重组制备的DAO。
在本发明中,“预防”意指防止与血液中高水平的组胺相关且以疼痛增加(包括偏头痛、慢性疲劳、纤维肌痛、脊椎炎和肌肉挛缩)为特征的疾病或病理状况的发作。
在本发明中,“治疗”意指在临床病理过程中进行的试图改变个体自然演化的临床干预。治疗的希望效果包括预防疾病复发、症状缓解、减少疾病的任何直接或间接的病理性后果、降低疾病的发展速率、改善或部分治疗病理状况,以及缓解或改善预后。
发明内容
本发明要解决的问题含有DAO的功能性食品的缺乏,所述功能性食品可预防或治疗与血液中高组胺水平相关的疾病或病理状况。具体地,这些疾病是偏头痛、慢性疲劳、纤维肌痛,脊椎炎和由肌肉挛缩引起的疼痛。
该食品可以是任何类型的乳制品。所述乳制品可以是酸奶、乳状饮料、糖果类产品、冰淇淋或其他任何饮料例如果汁。还可以是任何乳制品替代物,如豆乳、燕麦乳、杏仁乳或米浆等。
该食品还可以是任何类型的谷物、麦片(muesli)等。DAO还可以加入到植物油、动物和植物脂肪、黄油、人造黄油等中。
DAO可以游离形式、以粉末、冻干粉末、微粒、微胶囊、纳米胶囊或脂质体的形式加入食品中。
上述形式的DAO还可以加入营养补充剂中,例如含有ω-3脂肪酸、维生素、矿物质、氨基酸等的胶囊。
具体实施方式
本发明涉及一种含DAO的功能性食品。
本发明的一个实施方案是一种含游离形式、粉末、冻干粉末、微粒、微胶囊、纳米胶囊或脂质体形式的DAO的乳制品类功能性食品。
所述功能性食品的另一个实施方案是含游离形式、粉末、冻干粉末、微粒、微胶囊、纳米胶囊或脂质体形式的DAO的乳制品替代物,例如豆乳、燕麦乳、杏仁乳或米浆等。
包含含游离形式、粉末、冻干粉末、微粒、微胶囊、纳米胶囊或脂质体形式的DAO的谷物和类似物的功能性食品也构成了本发明的另一个实施方案。
将DAO以游离形式、以粉末、冻干粉末、微粒、微胶囊、纳米胶囊或脂质体形式纳入食品和维生素补充剂中也被视为本发明的另一个目的。
这些食品中的DAO浓度相对于食品总重量计为0.01至5重量%的DAO,优选0.5至1重量%的DAO。
本发明中使用的DAO可以为生物技术来源或植物提取物或动物提取物。
本发明中使用的DAO可具有胃肠道保护作用以防止其在胃中降解。
覆盖微粒的肠溶包衣层在中性或碱性介质中快速崩解或溶解。
微粒芯可用DAO施加其上的糖或类似基质使之成惰性,或所述芯可已经包含与其他赋形剂混合的DAO。所述赋形剂可为单独或混合形式的粘合剂、表面活性剂、填充剂、崩解剂、碱性添加剂或其他可药用成分。所述粘合剂可为纤维素类,例如羟丙基甲基纤维素、羟丙基纤维素和羧甲基纤维素钠、聚乙烯吡咯烷酮、糖类、淀粉和其他基于粘着性能的可药用物质。合适的表面活性剂见于可接受的非离子型或离子型表面活性剂类,例如十二烷基硫酸钠。
或者,DAO可与碱性化合物混合,并且可与待配制到芯物质中的合适成分进一步混合。所述芯物质可通过使用不同加工设备挤出/滚圆或压缩来制备。
DAO还可以与药学上可接受的碱混合,所述碱为例如磷酸盐、钠盐、钾盐、钙盐、镁盐和铝盐、碳酸、柠檬酸或其他合适的弱有机酸或无机酸;氢氧化铝/碳酸氢钠的共沉淀物;通常用于抗酸制剂中的物质,例如氢氧化铝、氢氧化钙和氢氧化镁、氧化镁或复合物质,例如Al2O3.6MgO.CO2.12H2O、(Mg6Al2(OH)16CO3.4H2O、MgO.Al2O3.2SiO2.nH2O或类似化合物;pH缓冲物质,例如三羟甲基氨基甲烷、碱性氨基酸及它们的盐或其他可药用pH缓冲物质。
所述肠溶包衣层可包含可药用增塑剂以获得所需的柔韧性和硬度的机械性质。这些增塑剂可以为,例如,三乙酸甘油酯、柠檬酸酯、邻苯二甲酸酯、鲸蜡醇、聚乙二醇、聚山梨醇酯或其他增塑剂。
将所述微粒仅通过混合加入固体功能性食品中,以及将微粒通过使它们共同振荡而加入到液体食品中,由此使它们保持在悬浮液中。
本发明还涉及本发明的含DAO的功能性食品用于预防或治疗与血液中高组胺水平相关的疾病或病理状况。
本发明还涉及本发明的含DAO的功能性食品用于预防或治疗偏头痛的用途。
本发明还涉及本发明的含DAO的功能性食品用于预防或治疗慢性疲劳、纤维肌痛、脊椎炎和由肌肉挛缩引起的疼痛。
此外,本发明还涉及用于预防或治疗与血液中高组胺水平相关的疾病或病理状况的含DAO的功能性食品。本发明还涉及用于预防或治疗偏头痛的含DAO的功能性食品。本发明还涉及用于预防或治疗慢性疲劳、纤维肌痛、脊椎炎和由肌肉挛缩引起的疼痛的含DAO的功能性食品。
本发明还涉及DAO用于制备用于预防或治疗与血液中高组胺水平相关的疾病或病理状况的本发明任一实施方案的功能性食品的用途。具体地,所述疾病或病理状况为偏头痛、慢性疲劳、纤维肌痛、脊椎炎和由肌肉挛缩引起的疼痛。
实施例
以下实施例进一步对本发明进行说明。
实施例1
根据以下配方制备含4%DAO的微粒:
DAO | 4mg |
甘露醇 | 40mg |
微晶纤维素 | 25mg |
羟丙基纤维素 | 10mg |
玉米淀粉 | 10mg |
柠檬酸 | 6mg |
所述微粒用羟丙基甲基纤维素进行包衣。
实施例2
制备以下含DAO的脱脂乳悬浮液:
A.10g含10%DAO的微粒
B.2.5g阿拉伯树胶在100g水中且完全水合的分散液
C.830g用脱脂乳粉末制备的脱脂乳
D.0.15gκ角叉胶(carrageenan)
将最终产物的pH调整到6.6至7.0,进行UHT灭菌并均质化。该乳在2℃至高达室温的贮存过程中是稳定的,未呈现出沉降(sedimentation)。
实施例3
制备以下含DAO的杏仁乳悬浮液:
A.15g含10%DAO的微粒
B.2.5g阿拉伯树胶在100g水中且完全水合的分散液
C.830g由杏仁乳粉末制备的杏仁乳
D.0.15gκ角叉胶
将最终产物的pH调整到6.6至7.0,进行UHT灭菌并均质化。该乳在2℃至高达室温的贮存过程中是稳定的,未呈现出沉降。
实施例4
制备胶囊形式的混有实施例1的DAO微粒的食品补充剂。对于350mg胶囊而言:
A.25mg含10%DAO的微粒
B.125mg含20%ω-3脂肪酸的鱼油粉末
C.1.25mg维生素PP(烟酸)
D.5mg硬脂酸镁
E.93.75mg
实施例5
用以下组分制备含DAO微粒的蔬菜饮料:
A.1.5g含10%DAO的微粒
B.1g稳定剂(1:1:1的果胶、瓜尔胶和角豆粉(carob seed flour)的混合物)
C.70g来自蔬菜(主要为番茄)的纤维状物质
D.100g用番茄和胡萝卜制成的蔬菜泥
E.50g蔬菜汁浓缩物(番茄、辣椒、芹菜和甜菜根)
F.90g果糖糖浆
G.20g经乳酸发酵的浓缩物
H.2g天然蔬菜和香料调味剂
将所有成分用水加至600g并搅拌。随后在搅拌下均质化、脱气并装入瓶中。
实施例7
将含有DAO的功能性食品——其为本发明的一个目的——给予总共48名受试者(20名男性和28名女性,其年龄在23至65岁之间),给药予方案为每日一次,共4周。对这些患者另外给予富含高组胺含量的食品的膳食(奶酪、巧克力、罐头鱼等)。在一组30名接受相同膳食(基于不具有任何DAO含量的食品)的受试者中,平行测量血液中的组胺水平。
为了证明含有DAO的食品对血液中组胺水平的影响,对摄入食品前和摄入食品后4周期间的组胺水平进行分析。血液中组胺值在每分升血液2至20微克组胺之间时被认为是正常的。血液中组胺值在每分升血液超过20微克组胺时被认为是较高的。
Claims (10)
1.一种含DAO的功能性食品。
2.根据权利要求1的含DAO的功能性食品,其特征在于,DAO可以游离形式、以粉末、冻干粉末、微粒、微胶囊、纳米胶囊或脂质体的形式加入食品中。
3.根据权利要求1或2的功能性食品,其特征在于,DAO为生物技术来源以及来自植物或动物提取物。
4.根据权利要求1或3任一项的功能性食品,其特征在于,DAO包括胃肠道保护。
5.根据权利要求1或4任一项的功能性食品,其特征在于,所述食品为乳制品基产品,例如酸奶、乳状饮料、糖果类产品、冰淇淋或其他饮料例如果汁;非乳制品基产品,例如豆乳、燕麦乳、杏仁乳或米浆;谷物等。
6.根据权利要求1或4任一项的功能性食品,其特征在于,所述食品为营养补充剂或维生素补充剂。
7.根据权利要求1或6任一项的功能性食品,其特征在于,DAO存在的百分比相对于食品总重量计为0.01至5重量%的DAO。
8.根据权利要求1或7任一项的功能性食品,其用于预防或治疗与血液中高组胺水平相关的疾病或病理状况。
9.根据权利要求1或7任一项的功能性食品,其用于预防或治疗偏头痛。
10.根据权利要求1或7任一项的功能性食品,其用于预防或治疗慢性疲劳、纤维肌痛、脊椎炎和由肌肉挛缩引起的疼痛。
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PCT/IB2012/051253 WO2012127382A1 (en) | 2011-03-18 | 2012-03-15 | Functional foods comprising diamine oxidase and uses thereof |
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CN107177642B (zh) * | 2017-06-12 | 2019-10-29 | 浙江大学宁波理工学院 | 一种咪唑-4-乙酸的生物合成方法 |
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CO6801744A2 (es) | 2013-11-29 |
US20170224784A1 (en) | 2017-08-10 |
ES2388166A1 (es) | 2012-10-09 |
US20130344137A1 (en) | 2013-12-26 |
WO2012127382A1 (en) | 2012-09-27 |
EP2685841A1 (en) | 2014-01-22 |
RU2634969C2 (ru) | 2017-11-08 |
BR112013023699A2 (pt) | 2016-08-09 |
RU2013144968A (ru) | 2015-04-27 |
US20220143151A1 (en) | 2022-05-12 |
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