CN109535023B - 一种dtpa偏中性盐及其制备方法与应用 - Google Patents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
- C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- G—PHYSICS
- G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
- G21F—PROTECTION AGAINST X-RADIATION, GAMMA RADIATION, CORPUSCULAR RADIATION OR PARTICLE BOMBARDMENT; TREATING RADIOACTIVELY CONTAMINATED MATERIAL; DECONTAMINATION ARRANGEMENTS THEREFOR
- G21F9/00—Treating radioactively contaminated material; Decontamination arrangements therefor
- G21F9/28—Treating solids
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Abstract
本发明涉及DTPA偏中性盐合成技术领域,公开一种DTPA偏中性盐与制备方法,具有通用结构:其中R为Na、K、NH4任意一种,所述制备方法先控制温度在35℃以下,将氢氧化钠溶液滴加到氯乙酸溶液中;再滴加二乙烯三胺,完毕后,向混合液中滴加氢氧化钠溶液;将混合液温度控制在30~40℃,使用体积浓度为50%的盐酸溶液调节混合液pH值至1.5~1.7,静置过夜,抽滤、冰水洗、烘干,得到DTPA;将上述得到的DTPA与碱液或强碱弱酸盐溶液反应,控制反应温度在40~60℃;最后将混合液温度升高至80~90℃,反应1~3h,蒸发至过饱和、乙醇结晶、抽滤、乙醇洗涤、干燥,最终得到DTPA偏中性盐;该方法制备出具有高效络合能力、可溶、稳定、无刺激、高纯度的DTPA偏中性盐;并提供该DTPA偏中性盐的应用。
Description
技术领域
本发明涉及DTPA偏中性盐合成技术领域,具体涉及一种DTPA偏中性盐及其制备方法与应用。
背景技术
随着环境污染的日趋严重化,人们接触重金属(包括放射性金属核素)的概率越来越高。重金属离子接触皮肤后,有微量的离子渗入皮下,进入组织,长时间的累积会对人体造成严重影响。另外体表的重金属离子可以通过很多方式进入体内(比如:吸入、食入),损害人体健康,对人体的伤害极大,不同金属对人体各器官的影响不同。如果此重金属具有放射性,除可能会进入体内形成内照射外,其粘附在体表也会形成长时间的外照射,增加人体的患病概率,因此需要对其进行高效的洗消处理。
二乙烯三胺五乙酸(DTPA)作为一种重要的氨羧络合剂,它对金属离子,尤其对高价态显色金属离子的络合能力非常强,且络合能力、稳定性、抗氧化性均强于EDTA等络合剂,而在实际应用中其五钠盐应其具有可溶性以及很强的络合能力常被使用。但二乙烯三胺五乙酸五钠具有强碱性,pH值达到11.2~11.5,对皮肤具有极强的刺激性(因为人体皮肤表面显弱酸性),不能应用于人体体表的重金属以及放射性金属核素的洗消,因此需要制备高纯度DTPA偏中性盐,且保证具有非常强的络合能力以及溶解性。
目前DTPA工业生产方法有以下两种:第一种方法是氯乙酸法,例如中国发明专利申请文件公告号为CN101607921A一种二乙三胺五醋酸的制备方法、二乙烯三胺五乙酸五钠合成工艺的研究(《化学工业与工程技术》(2008.29.(1).18-19))、DTPA螯合剂及其制造(《纸和造纸》(2005.3.63-64))、DTPA合成工艺的研究(《造纸化学品》(1997.9(4).7-10))、造纸化学品DTPA的合成研究(《中国造纸》(1997.5.68-69))等文献都介绍了该方法,该方法采用氯乙酸、二乙烯三胺和氢氧化钠或碳酸钠等原料合成,其工艺较简单,但在生产过程中会产生大量的副产物氯化钠,需要对得到的DTPA粗品进行脱盐提纯,此外,生产过程中氯乙酸易于水解,严重影响DTPA收率。
第二种方法是氰化钠法,例如DTPA合成方法的研究(《皮革化工》(2002.19.(5).26-28))、二乙三胺五乙酸的合成(《化学工业与工程技术》(2006.27.(6).24-25))等文献介绍了该方法,采用氰化钠与甲醛及二乙烯三胺等原料合成,该方法的优点是操作简便,成本较低,产品质量好,不产生副产物氯化钠,但是该方法使用了剧毒的氰化物作为原料,使得生产管理不易控制。
目前国内生产DTPA大多采用氯乙酸法,但是普遍收率较低,文献报道的收率大都在80%以下,另外杂质含量高、盐分多、精制工艺落后,在市场上无法与国外同类产品竞争。并且,市场上暂无高效络合性、可溶性的高纯度DTPA偏中性盐的相关产品,且无相关的文献报道,因此一种DTPA偏中性盐及其制备方法具有重要的现实意义。
发明内容
本发明的目的在于提供一种DTPA偏中性盐与制备方法,该方法制备出具有高效络合能力、可溶、稳定、无刺激、高纯度的DTPA偏中性盐;并提供该DTPA偏中性盐的应用。
为了实现上述发明目的,本发明采用的技术方案如下:
1)控制温度在35℃以下,将氢氧化钠溶液滴加到氯乙酸溶液中,保持反应体系温度持续在35℃以下;
2)在步骤1)的反应体系中滴加二乙烯三胺,滴加完毕后,向混合液中滴加氢氧化钠溶液,pH值达到11.2~11.5时结束滴定,升高温度至55~65℃,反应7~9h,重新测定pH值,使稳定pH处于11.2~11.5范围;
3)将步骤2)混合液温度降至30~40℃,使用体积浓度为50%的盐酸溶液调节所述混合液pH值至1.5~1.7,静置过夜,抽滤、冰水洗、烘干,得到DTPA;
4)将步骤3)得到的DTPA与碱液或强碱弱酸盐溶液反应,控制反应体系温度在40~60℃;
5)将步骤4)的混合体系温度升高至80~90℃,反应1~3h,蒸发至过饱和、乙醇结晶、抽滤、乙醇洗涤、干燥,最终得到DTPA偏中性盐。
在本发明中,进一步的,所述步骤1)中的氢氧化钠与氯乙酸的摩尔比为0.43~0.57:1;所述氢氧化钠溶液的摩尔浓度为8~10mol/L;所述氯乙酸溶液的摩尔浓度为10~15mol/L。
在本发明中,进一步的,所述步骤1)中温度控制在-20~35℃。
在本发明中,进一步的,所述步骤2)中二乙烯三胺与氯乙酸的摩尔比为1:5~5.1。
在本发明中,进一步的,所述氢氧化钠溶液的浓度为24%~26%。
在本发明中,进一步的,所述步骤4)中碱液或强碱弱酸盐溶液为氢氧化钠、碳酸钠、碳酸氢钠、氢氧化钾、碳酸钾、碳酸氢钾、氨水中一种。
在本发明中,进一步的,所述步骤5)中得到DTPA偏中性盐可洗消体表的重金属和放射性金属核素有铯离子、镁离子、钙离子、锶离子、钡离子、镭离子、锡离子、铅离子、镓离子、铟离子、铊离子、锑离子、钋离子、铋离子、钴离子、钍离子、铀离子以及过渡金属离子。
在本发明中,进一步的,所述DTPA偏中性盐适用于体表重金属洗消。
在本发明中,进一步的,所述DTPA偏中性盐适用于体表放射性金属核素洗消。
由于采用了上述技术方案,本发明的有益效果是:
(1)本发明制备方法制备的DTPA盐,弱酸性、偏中性,与人体体表酸碱环境相一致或接近,无刺激;本发明制备方法先在氯乙酸溶液中先加入氢氧化钠溶液进行中和,使得氯乙酸钠不易发生水解,减少了由于氯乙酸钠的水解副反应而需控制反应物二乙烯三胺的量,同时使得二乙烯三胺与氯乙酸的反应速度较水解反应快,对合成目标产物DTPA偏中性盐起到一定的促进作用;另外,本方法的过程严格控制各步骤的温度与pH值,产品质量好,副产物少,目标产物DTPA偏中性盐的纯度高达99.9%;
(2)本发明首次针对体表重金属和放射性金属核素洗消提出一种高纯度的DTPA偏中性盐及其制备方法,通过此方法可制备出具有极好可溶性、稳定性、络合能力,对表皮无刺激性的DTPA偏中性盐,且能够高效洗消粘附在体表的重金属离子和放射性金属核素。
附图说明
图1为本发明DTPA 3Na的制备流程图。
图2为本发明DTPA 3Na的1H-NMR谱图。
图3为本发明DTPA 3Na的13C-NMR谱图。
图4为本发明DTPA 3Na的质谱图。
图5为本发明DTPA 3Na的X射线光电子谱图,经测试符合产物元素要求。
图6为本发明DTPA 3Na的电感耦合等离子体原子发射光谱图,经测试Na含量约为15.0%。
具体实施方式
为了使本发明实现的技术手段、创作特征、达成目的与功效易于明白了解,下面结合实施例,进一步阐述本发明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。
本发明所用的原料均可从市面上购买。
实施例一
一种DTPA偏中性盐的制备方法:称取氯乙酸94.5g,溶于74.5g蒸馏水,40.0g氢氧化钠溶于120g蒸馏水,搅拌下并控制温度在35℃以下,向氯乙酸溶液逐滴加入80g氢氧化钠溶液,滴加过程保持反应体系温度在35℃以下,向混合液中滴加20.634g二乙烯三胺,之后向溶液中滴加剩余氢氧化钠溶液,当pH值达到11.2~11.5时结束滴定,升高温度至55℃,反应9h,降低温度至35℃,使用体积浓度为50%的盐酸溶液调节pH值至1.5~1.7,静置过夜,抽滤、蒸馏水洗涤3次、120℃烘干,得到DTPA,纯度为99.82%;称取12g氢氧化钠溶于480g蒸馏水,39.34g DTPA分散于196.7g蒸馏水,在剧烈搅拌条件下将氢氧化钠溶液逐滴加入到DTPA分散液中,控制反应体系温度在40~60℃,滴加完毕温度升高至80℃,反应1h,蒸发至溶液剩余总体积的1/5后冷却、向溶液中加入无水乙醇200mL、抽滤、乙醇洗涤3次、140℃干燥、粉碎,得到主要产物,经滴定测试纯度为99.92%,通过结构分析,确定此化合物为DTPA3Na。对模仿体表放射性铯离子污染的洗消效果良好,一次清洗去除率达到99.2%。
实施例二
一种DTPA偏中性盐的制备方法:称取氯乙酸94.5g,溶于74.5g蒸馏水,40.0g氢氧化钠溶于120g蒸馏水,搅拌下并控制温度在35℃以下,向氯乙酸溶液逐滴加入70g氢氧化钠溶液,滴加过程保持反应体系温度在35℃以下,向混合液中滴加20.634g二乙烯三胺,之后向溶液中滴加剩余氢氧化钠溶液,当pH值达到11.2~11.5时结束滴定,升高温度至60℃,反应8h,降低温度至35℃,使用体积浓度为50%的盐酸溶液调节pH值至1.5~1.7,静置过夜,抽滤、蒸馏水洗涤3次、120℃烘干,得到DTPA,纯度为99.90%;称取15.9g碳酸钠溶于160g蒸馏水,39.34g DTPA分散于196.7g蒸馏水,在剧烈搅拌条件下将碳酸钠溶液逐滴加入到DTPA分散液中,控制反应体系温度在40~60℃,滴加完毕温度升高至80℃,反应2h,蒸发至溶液剩余总体积的1/5后冷却、向溶液中加入无水乙醇200mL、抽滤、乙醇洗涤3次、140℃干燥、粉碎,得到主要产物,经滴定测试纯度为99.96%,通过结构分析,确定此化合物为DTPA 3Na。对模仿体表放射性铯离子污染的洗消效果良好,一次清洗去除率达到99.7%。
实施例三
一种DTPA偏中性盐的制备方法:称取氯乙酸94.5g,溶于74.5g蒸馏水,40.0g氢氧化钠溶于120g蒸馏水,搅拌下并控制温度在35℃以下,向氯乙酸溶液逐滴加入90g氢氧化钠溶液,滴加过程保持反应体系温度在35℃以下,向混合液中滴加20.634g二乙烯三胺,之后向溶液中滴加剩余氢氧化钠溶液,当pH值达到11.2~11.5时结束滴定,升高温度至65℃,反应7h,降低温度至35℃,使用体积浓度为50%的盐酸溶液调节pH值至1.5~1.7,静置过夜,抽滤、蒸馏水洗涤3次、120℃烘干,得到DTPA,纯度为99.88%;称取25.2g碳酸氢钠溶于400g蒸馏水,39.34g DTPA分散于196.7g蒸馏水,在剧烈搅拌条件下将碳酸氢钠溶液逐滴加入到DTPA分散液中,控制反应体系温度在40~60℃,滴加完毕温度升高至80℃,反应2h,蒸发至溶液剩余总体积的1/5后冷却、向溶液中加入无水乙醇200mL、抽滤、乙醇洗涤3次、140℃干燥、粉碎,得到主要产物,经滴定测试纯度为99.94%,通过结构分析,确定此化合物为DTPA3Na。对模仿体表放射性铯离子污染的洗消效果良好,一次清洗去除率达到99.5%。
对合成的化合物进行测定:1H-NMR谱图中(如图2所示)δ3.83(s,8H)单峰归属于a位置氢的化学位移值,δ3.39(t,J=6.6Hz,4H)三重峰归属于b位置氢的化学位移值,δ3.28(s,2H)单峰归属于c位置氢的化学位移值,δ3.05(t,J=6.6Hz,4H)三重峰归属于d位置氢的化学位移值。13C-NMR谱图中(如图3所示)δ178.34归属于a位置碳的化学位移值,δ170.55归属于b位置碳的化学位移值,δ56.95归属于c位置碳的化学位移值,δ56.15归属于d位置碳的化学位移值,δ52.88归属于e位置碳的化学位移值,δ49.10归属于f位置碳的化学位移值,对应6种碳的位移值。质谱图中(如图4所示)分子离子峰有m/z 436.1、m/z 206.5,分别为[M-Na]-和[M-2Na]2-。同时,发生Na+和H+交换为含5个羧基的多元酸:C14H23N3O10(精确分子量为393.1378)。质谱图中分子离子峰m/z 392.1、m/z195.5,分别为[M-H]-和[M-2H]2-。核磁与质谱的检测结果符合化合物的结构要求。X射线光电子谱图中(如图5所示)可以得出化合物存在C、N、O、Na元素,经电感耦合等离子体原子发射光谱准确测定Na元素百分含量(如图6所示),其值约为15.0%,符合DTPA 3Na中Na元素含量的要求。结合以上分析,确定此化合物为DTPA 3Na。
下面通过具体实验进一步验证本发明的DTPA偏中性盐作用:
1、将本实施例一-三制备的DTPA偏中性盐溶于水,得到不同浓度的DTPA溶液,于25℃的条件下,采用同一pH计依次测定其pH值(本实验中pH计生产厂家为梅特勒-托利多),具体数据如表1所示:
表1
注:①上述数据为测试5次的平均值。
由表1可知,采用本发明实施例1-3的DTPA盐,弱酸性、偏中性。
2、将本实施例一-三制备的DTPA偏中性盐制备成肥皂,制备方法:在搅拌容器中加入常用的肥皂原料1000g,所述肥皂原料包括脂肪酸钠皂、硬脂酸、三乙醇胺、甘油和丙二醇,在搅拌下完全反应,静止0.5h;然后加入30g(添加量为肥皂原料的3.0%)本实施例一-三制备的DTPA偏中性盐;混合均匀、注模、快速冷却20min,切条、晾干、洗磨、打印;最后,包装后得到实施例1-3肥皂成品。
对比例1:一种壳聚糖肥皂,其专利公开号为CN100419055C,该壳聚糖肥皂来洗脸、洗手或者洗澡,保湿效果理想,洗后无紧绷感,且可络合人体表面的重金属,具有抗辐射和抗皱等功效;其制备方法:在搅拌容器中加入常用的肥皂原料1000g,所述肥皂原料包括脂肪酸钠皂、硬脂酸、三乙醇胺、甘油和丙二醇,在搅拌下完全反应,静止0.5h;然后加入30g壳聚糖和0.5g磺化壳聚糖;注模、快速冷却20min,切条、晾干、洗磨、打印;最后,包装后得到对比例1肥皂成品。
将上述实施例1-3和对比例1的肥皂成品,依次进行模仿体表放射性铯离子污染的洗消试验,具体数据如表2所示:
表2
注:①上述数据为测试5次的平均值。
由表1可知,采用本发明实施例1-3肥皂成品与对比例1肥皂成品进行模仿洗消体表放射性铯离子污染,洗消效果好,一次清洗去除率均高达到99.2%,比对比例1高出分别高出16.9%、17.4%和17.2%,说明本发明制备DTPA偏中性盐的可溶性好、络合能力强,且能够高效洗消粘附在体表的重金属离子和放射性金属核素。
本发明并不局限于前述的具体实施方式。本发明扩展到任何在本说明书中披露的新特征或任何新的组合,以及披露的任一新的方法或过程的步骤或任何新的组合。
Claims (7)
2.根据权利要求1所述的一种DTPA偏中性盐的应用,其特征在于,所述DTPA偏中性盐的制备方法包括以下步骤:
1)控制温度在35℃以下,将氢氧化钠溶液滴加到氯乙酸溶液中,保持反应体系温度持续在35℃以下;
2)在步骤1)的反应体系中滴加二乙烯三胺,滴加完毕后,向混合液中滴加氢氧化钠溶液,pH值达到11.2~11.5时结束滴定,升高温度至55~65℃,反应7~9 h,重新测定pH值,使稳定pH处于11.2~11.5范围;
3)将步骤2)混合液温度降至30~40℃,使用体积浓度为50%的盐酸溶液调节所述混合液pH值至1.5~1.7,静置过夜,抽滤、冰水洗、烘干,得到DTPA;
4)将步骤3)得到的DTPA与碱液或强碱弱酸盐溶液反应,控制反应体系温度在40~60℃;
5)将步骤4)的混合体系温度升高至80~90℃,反应1~3 h,蒸发至过饱和、乙醇结晶、抽滤、乙醇洗涤、干燥,最终得到DTPA偏中性盐。
3.根据权利要求2所述的一种DTPA偏中性盐的应用,其特征在于:所述步骤1)中的氢氧化钠与氯乙酸的摩尔比为0.43~0.57:1;所述氢氧化钠溶液的摩尔浓度为8~10 mol/L;所述氯乙酸溶液的摩尔浓度为10~15 mol/L。
4.根据权利要求2所述的一种DTPA偏中性盐的应用,其特征在于:所述步骤1)中温度控制在-20~35℃。
5.根据权利要求2所述的一种DTPA偏中性盐的应用,其特征在于:所述步骤2)中二乙烯三胺与氯乙酸的摩尔比为1:5~5.1。
6.根据权利要求2所述的一种DTPA偏中性盐的应用,其特征在于:所述氢氧化钠溶液的浓度为24%~26%。
7.根据权利要求2所述的一种DTPA偏中性盐的应用,其特征在于:所述步骤4)中碱液或强碱弱酸盐溶液为氢氧化钠、碳酸钠、碳酸氢钠中一种。
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