CN110105465B - 一种膦酸海带多糖铁及其制备方法 - Google Patents
一种膦酸海带多糖铁及其制备方法 Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/16—Inorganic salts, minerals or trace elements
- A23L33/165—Complexes or chelates
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Molecular Biology (AREA)
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- Food Science & Technology (AREA)
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Abstract
本发明涉及一种膦酸海带多糖铁及其制备方法。包括以下步骤:将海带多糖与氨基亚乙基二膦酸混合,在‑7℃‑13℃温度下滴加二氯亚砜,滴加完毕后继续反应1‑3小时,然后自然升至室温10‑14小时,再于50‑70℃下旋转蒸发得到膦酸海带多糖;将膦酸海带多糖用蒸馏水溶解,在50‑60℃恒温水浴条件下加入柠檬酸铁,并滴加20%氢氧化钠溶液调节反应体系pH值至89;滴加完成后继续搅拌反应3‑5小时;离心取上清液,对其进行醇沉、离心、洗涤、干燥处理后得到膦酸海带多糖铁。本发明采用操作简便的合成方法,在较低温度下合成磷酸根含量和铁含量较高的膦酸海带多糖铁,在实际应用过程中具有独特的优势。
Description
技术领域
本发明涉及一种膦酸海带多糖铁及其制备方法,属于多糖衍生物技术领域。
背景技术
海洋蕴涵着生物种类的80%以上,是生物多样性的巨大储存库。我国海洋资源丰富,烟台地处胶东半岛,是中国重要的海带养殖生产基地。但目前,我国对海带多糖的研究还有待深入,需要为其产业化建立完善的技术平台,从而综合利用我国的海带资源,为功能性食品及新药的开发奠定基础。大量的报道表明,海带中含有丰富的多糖类物质,海带多糖在抗高血脂、抗病毒、抗菌、抗疲劳、抗辐射以及消除自由基和抗氧化方面发挥了不可忽视的作用。多糖的活性直接或间接受其分子结构的影响,采用一定的方法对多糖分子结构进行修饰可以提高或赋予多糖活性。多糖经过分子修饰后可以设计合成出多种新型结构与功能的多糖衍生物,可以为多糖类食品添加剂、功能性食品、保健品及药物的研究开发奠定基础。
文献资料中对海带多糖类衍生物的报道中,仅见有少量文献报道磷酸化海带多糖,其操过程较复杂,且含磷量较低。例如使用多聚磷酸在碱性条件下对海带褐藻多糖硫酸酯进行磷酸化反应,相关产品磷酸根含量最高能达到9.62%。现有技术中对于天然多糖的磷酸功能化方法,主要使用的是磷酰氯、磷酸酐、磷酸或磷酸盐,反应实验条件比较容易引起多糖的降解,或者会伴随着交联等副反应产生,使产物复杂化。
另外,缺铁性贫血是由于饮食中铁含量不足、身体对铁吸收不良和铁的过量损耗而产生的现代社会普遍存在的营养性疾病。据世界卫生组织调查,成年女性的缺铁性贫血发病率高于男性,尤其是以孕妇的发病率为最高,儿童也是缺铁性贫血的多发群体。缺铁性贫血患者会出现乏力、厌食、免疫力下降等症状,严重影响身体健康。口服补铁剂廉价、有效,是治疗和预防人体缺铁性贫血的最佳选择。作为目前国际上最新的第三代补铁剂,多糖铁配合物可以很好地被人体吸收,减少肠胃刺激,具有较高的稳定性和较少的副作用,是具有应用价值的治疗缺铁性贫血药物。目前制备多糖铁的方法主要是氯化铁法、改良氯化铁法、硫酸铁胺法和模拟生物矿化法,其相关实验操作比较复杂,反应温度相对较高。
发明内容
本发明针对上述现有技术的不足,提供一种膦酸海带多糖铁的制备方法。采用该方法制备操作简便,在较低温度实验条件下即可合成磷酸根含量和铁含量较高的膦酸海带多糖铁。
一种膦酸海带多糖铁的制备方法,包括以下步骤:
1)将海带多糖与氨基亚乙基二膦酸混合,在-7℃-13℃温度下滴加二氯亚砜,滴加完毕后继续反应1-3小时,然后自然升至室温10-14小时,再于50-70℃下旋转蒸发得到膦酸海带多糖;
2)将步骤1)所制备的膦酸海带多糖用蒸馏水溶解,在50-60℃恒温水浴条件下加入柠檬酸铁,并滴加20%氢氧化钠溶液调节反应体系pH值至8-9;滴加完成后继续搅拌反应3-5小时;离心取上清液,对其进行醇沉、离心、洗涤、干燥处理后得到膦酸海带多糖铁。
优选的,所述步骤1)中海带多糖和氨基亚乙基二膦酸的质量比为1:(1-3),海带多糖与二氯亚砜的质量比为1: (5-7)。
优选的,所述步骤2)中膦酸海带多糖与柠檬酸铁的质量比为1: (2-4)。
本发明还提供一种膦酸海带多糖铁,采用上述方法制备获得。
有益效果:本发明采用的是一种操作简便的合成方法,在较低温度实验条件下合成磷酸根含量和铁含量较高的膦酸海带多糖铁,操作简便易行,成本低廉,合成温度较低,可节约能源,便于工业化和技术推广,在实际应用过程中具有独特的优势。具体为,本发明先在低温条件下制得膦酸海带多糖,可有效地提高海带多糖衍生物中的磷酸根含量,从而提高其活性。继而在此基础之上成功制备得到膦酸海带多糖铁,可有效提高铁含量,用作大分子复合物补铁剂。
具体实施方式
以下对本发明的原理和特征进行描述,所举实例只用于解释本发明,并非用于限定本发明的范围。
本发明所述试剂信息如下:
海带多糖:卡迈舒生物科技有限公司、BR。
氨基亚乙基二膦酸:实验室自制。
二氯亚砜:国药集团化学试剂有限公司、分析纯AR。
柠檬酸铁:国药集团化学试剂有限公司、分析纯AR。
尿素:天津市瑞金特化学品有限公司、分析纯AR。
氯化铁:天津市瑞金特化学品有限公司、分析纯AR。
实施例1
将海带多糖与氨基亚乙基二膦酸混合,在-9℃温度下滴加二氯亚砜,滴加完毕后继续反应2小时,海带多糖和氨基亚乙基二膦酸的质量比为1:2,海带多糖与二氯亚砜的质量比为1: 6。然后自然升至室温12小时,再于60℃下旋转蒸发得到膦酸海带多糖。将其用蒸馏水溶解中,在恒温(56℃)水浴条件下加入柠檬酸铁,膦酸海带多糖与柠檬酸铁的质量比为1: 3,并滴加20%氢氧化钠溶液调节反应体系pH值至pH=9。滴加完成后继续搅拌反应4小时。离心取上清液,对其进行醇沉、离心、洗涤、干燥处理后得到膦酸海带多糖铁1。
实施例2
将海带多糖与氨基亚乙基二膦酸混合,在-13℃温度下滴加二氯亚砜,滴加完毕后继续反应3小时,海带多糖和氨基亚乙基二膦酸的质量比为1: 1,海带多糖与二氯亚砜的质量比为1: 5。然后自然升至室温10小时,再于50℃下旋转蒸发得到膦酸海带多糖。将其用蒸馏水溶解中,在恒温(50℃)水浴条件下加入柠檬酸铁,膦酸海带多糖与柠檬酸铁的质量比为1: 2,并滴加20%氢氧化钠溶液调节反应体系pH值至pH=8。滴加完成后继续搅拌反应3小时。离心取上清液,对其进行醇沉、离心、洗涤、干燥处理后得到膦酸海带多糖铁2。
实施例3
将海带多糖与氨基亚乙基二膦酸混合,在-11 ℃温度下滴加二氯亚砜,滴加完毕后继续反应2小时,海带多糖和氨基亚乙基二膦酸的质量比为1: 3,海带多糖与二氯亚砜的质量比为1: 5。然后自然升至室温14小时,再于70℃下旋转蒸发得到膦酸海带多糖。将其用蒸馏水溶解中,在恒温(54℃)水浴条件下加入柠檬酸铁,膦酸海带多糖与柠檬酸铁的质量比为1: 4,并滴加20%氢氧化钠溶液调节反应体系pH值至pH=9。滴加完成后继续搅拌反应5小时。离心取上清液,对其进行醇沉、离心、洗涤、干燥处理后得到膦酸海带多糖铁3。
实施例4
将海带多糖与氨基亚乙基二膦酸混合,在-12℃温度下滴加二氯亚砜,滴加完毕后继续反应2小时,海带多糖和氨基亚乙基二膦酸的质量比为1: 1.5,海带多糖与二氯亚砜的质量比为1: 7。然后自然升至室温12小时,再于60℃下旋转蒸发得到膦酸海带多糖。将其用蒸馏水溶解中,在恒温(52℃)水浴条件下加入柠檬酸铁,膦酸海带多糖与柠檬酸铁的质量比为1: 2,并滴加20%氢氧化钠溶液调节反应体系pH值至pH=8。滴加完成后继续搅拌反应3小时。离心取上清液,对其进行醇沉、离心、洗涤、干燥处理后得到膦酸海带多糖铁4。
对比例1:
室温下称取海带多糖与氨基亚乙基二膦酸混合,加入尿素,海带多糖、氨基亚乙基二膦酸和尿素的质量比为1:1:0.1,将三者混合均匀后加热到80℃反应6小时。之后将该混合物用蒸馏水溶解,在恒温(56℃)水浴条件下加入氯化铁,膦酸海带多糖与氯化铁的质量比为1: 3,并滴加20%氢氧化钠溶液调节反应体系pH值至pH=9。滴加完成后继续搅拌反应4小时。离心取上清液,对其进行醇沉、离心、洗涤、干燥处理后得到膦酸海带多糖铁对比样品。
通过本发明的制备方法,实现了通过操作简便的方法,在较低温度实验条件下合成制备得到磷酸根含量和铁含量较高的膦酸海带多糖铁。表1为实施例1-4及对比例1中的产品磷酸根含量和铁含量测定表。
本发明中的磷酸根的测定方法:以过硫酸铵为氧化剂,将有机磷转化为无机磷,钼钒酸盐为显色剂,采用钼蓝比色法测定磷酸根含量。
测定步骤如下:
(1)钼酸钠—硫酸溶液配制:将100mL浓硫酸慢慢地加到500mL水中,冷却至室温,得到A液;另称取10g钼酸钠溶于400mL水中,得到B液。然后将A液加到B液中,混匀。
(2)过硫酸铵—硫酸钠分解剂配制:称取0.8g过硫酸铵和4.2g无水硫酸钠混合均匀。
(3)称取适量样品并加入10mL蒸馏水于100mL锥形瓶中,加入1mL1M硫酸溶液及50mg过硫酸铵—硫酸钠分解剂,将锥形瓶放在置有石棉网的小电炉上均匀加热煮至溶液刚好干稠并刚冒浓厚白烟为止。
(4)稍冷,加入10mL水,4~40mg亚硫酸钠粉末或10滴甲醇,再在电炉上微沸30~60秒取下,将溶液小心转移到50mL比色管中,并用少量水冲洗原锥形瓶几次,洗液并入比色管中,溶液应控制在25mL左右。
(5)加入4mL钼酸钠—硫酸钠-硫酸溶液及1mL硫酸肼溶液,放入已煮沸的水浴中10分钟后取出,流水冷却,用水稀释至刻度,立即用1cm比色皿,在580nm波长处,以试剂空白作对照测定其吸光度,从标准曲线上查得相应磷酸盐的含量。
P=CV/m×100%
式中:
P------为样品中磷酸盐含量(%);
C------为580nm处所测吸光度在标准曲线上查得相应的磷酸根浓度;
V------为样品稀释的体积;
m------为样品的质量。
样品中铁含量的测定方法:以硫酸亚铁胺为标准品,采用邻菲啰啉分光光度法测定铁含量。准确称取样品10mg,加入1mol/L盐酸20mL,溶解24h后,取上述溶液1mL,依次加入10%盐酸羟胺溶液1mL,10%邻菲罗啉2.5mL,醋酸盐缓冲溶液(pH 4.5)5mL,混合均匀后定容静置30min,在510nm下测定吸光度。根据标准曲线回归方程求算出配合物中的铁含量。
配合物的铁含量%=m1/m*100
式中:m1为配合物中铁离子含量/g;m为配合物总量/g。
表1 实施例1-4及对比例中的产品磷酸根含量和铁含量测定表
产品 | 磷酸根含量 | 铁含量 |
实施例1 | 11.93% | 21.02% |
实施例2 | 10.89% | 19.24% |
实施例3 | 11.47% | 20.55% |
实施例4 | 11.08% | 19.71% |
对比例1 | 5.22% | 10.56% |
本发明在相对较低的温度条件下合成了膦酸海带多糖铁,磷酸功能基团的引入,为海带多糖构筑了一个带负电荷的亲水性表面结构,有效提高其水溶性及活性。磷酸多糖衍生物有减轻心功能不全症状、抗炎、抗氧化、抗菌免疫、抗肿瘤等功能,因此,膦酸海带多糖将会在免疫调节等生物活性及开发新型材料方面表现出潜在的应用前景。继而在膦酸海带多糖的基础之上成功制备得到膦酸海带多糖铁,并有效提高铁含量,用作大分子复合物补铁剂。由表1可看出,本发明所制备膦酸化海带多糖铁中的磷酸根含量较高,铁含量较高。在人体的肠腔内,铁离子必须与内源或外源配位体结合形成络合物,再以此形式吸收并进一步转运。考虑到配位强度需适宜的因素,本发明中修饰基团引入了氨基。体内细胞膜是由蛋白质和类脂组成,它是细胞内外环境的天然屏障。铁离子要穿过细胞膜,需要载体分子将其包被起来,形成有机层表面,才能穿过细胞膜,本发明使用功能有机膦酸修饰的海带多糖来作为其有效的载体。膦酸海带多糖铁作为补铁剂,不仅具有合适的络合配位稳定性,对肠胃无或者少刺激性,而且当其释放铁后,多糖本身具有多方面的生物活性,属于对机体有益的成分,可被吸收利用。
本发明采用的是一种操作较简便的方法,可在较低温度实验条件下合成磷酸根含量和铁含量较高的膦酸海带多糖铁,反应原料无毒、来源广、价格低,操作简便易行,合成温度较低可节约能源,便于将来的工业化和技术推广,在实际应用过程中具有独特的优势。
本发明可用其他的不违背本发明的精神或主要特征的具体形式来概述。因此,无论从哪一点来看,本发明的上述实施方案都只能认为是对本发明的说明而不能限制本发明,权利要求书指出了本发明的范围,而上述的说明并未指出本发明的范围,因此,在与本发明的权利要求书相当的含义和范围内的任何改变,都应认为是包括在本发明的权利要求书的范围内。
Claims (2)
1.一种膦酸海带多糖铁的制备方法,其特征在于,包括以下步骤:
1)将海带多糖与氨基亚乙基二膦酸混合,在-70C-130C温度下滴加二氯亚砜,滴加完毕后继续反应1-3小时,然后自然升至室温10-14小时,再于50-700C下旋转蒸发得到膦酸海带多糖;
所述海带多糖和氨基亚乙基二膦酸的质量比为1: (1~3),海带多糖与二氯亚砜的质量比为1: (5~7);
2)将步骤1)所制备的膦酸海带多糖用蒸馏水溶解,在50~600C恒温水浴条件下加入柠檬酸铁,并滴加20%氢氧化钠溶液调节反应体系pH值至8~9;滴加完成后继续搅拌反应3~5小时;离心取上清液,对其进行醇沉、离心、洗涤、干燥处理后得到膦酸海带多糖铁;
所述膦酸海带多糖与柠檬酸铁的质量比为1: (2~4)。
2.一种膦酸海带多糖铁,其特征在于,采用权利要求1所述方法制备获得。
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