CN113425614A - 氨基酸或氨基酸类似物或其盐在作为提高尿囊素溶解性能的添加剂的应用 - Google Patents
氨基酸或氨基酸类似物或其盐在作为提高尿囊素溶解性能的添加剂的应用 Download PDFInfo
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Abstract
本发明提供了一种氨基酸或氨基酸类似物或其盐在作为提高尿囊素溶解性能的添加剂的应用和一种高尿囊素含量的常温稳定溶液。发明人发现将氨基酸或氨基酸类似物或其盐、尿囊素、极性溶液按配比混合后,可通过加热法、蒸发法或冷冻干燥法制备得到澄清溶液,此澄清溶液在常温下稳定,与水可以任意比例混合且尿囊素不析出。本发明所制备的澄清溶液既能解决尿囊素溶解性能差的问题,又能大大提高尿囊素的应用效率及生物利用度。
Description
技术领域
本发明涉及化学领域,具体涉及氨基酸或氨基酸类似物或其盐的一种新用途及该新用途下得到的高尿囊素含量的常温稳定溶液。
背景技术
尿囊素学名为1-脲基间二氮戊烷-2,4-二酮或5-脲基已内酰胺。由于尿囊素最早在牛的尿囊液中发现,广泛存在于哺乳动物的尿液中和动植物的胚胎内,所以俗称尿囊素,分子式为C4H6N4O3,结构式如式(Ⅰ)所示。
由于尿囊素已经广泛应用于日化领域、医学领域、农业领域等,如复方肝素钠尿囊素凝胶、维生素E尿囊素乳膏等。但其常温下在水及醇中的溶解性均很低(饱和水溶液中约为0.4质量%),尽管加热可以使尿囊素在水或醇中的溶解性能稍微增加,但是当体系中冷却至常温后,尿囊素又析出,影响体系的均一性,因此尿囊素的应用效率及生物利用度受到了限制。
由于尿囊素溶解性的限制,在现有技术中,尿囊素在混合物体系中的含量一般不超过2%,例如CN110227044A中,公开一种HA胶原蛋白原液,其实施例中尿囊素的含量均在2%以下。为了提高尿囊素的添加量,CN111773131A采用特殊的工艺处理和油包水的结构,使高浓度的尿囊素可以分散在油脂中,得到均匀无颗粒感的膏霜,且避开了水的接触避免了析出晶体的现象,该体系中,尿囊素的含量可以高达3%。
尽管如此,尿囊素的溶解性能并未得到根本性的解决。尿囊素的使用仍因为难以在极性溶剂体系中溶解/分散而受到限制。
氨基酸,是含有碱性氨基和酸性羧基的有机化合物的统称。其结构多样,因此功能丰富,在农业、日化领域中有广泛的使用。但未有关于氨基酸或其类似物改善尿囊素溶解性的报道。
发明内容
本发明的目的在于克服现有技术的不足,提供一种氨基酸或其盐或其类似物的新用途。
本发明的另一目的在于提供一种提高尿囊素在极性溶剂中的溶解性能的方法。
本发明的另一目的在于提供一种高尿囊素含量的常温稳定溶液。
本发明的另一个目的在于提供所述高尿囊素含量的常温稳定溶液的制备方法。
本发明的另一个目的在于提供所述高尿囊素含量的常温稳定溶液的应用。
本发明上述目的通过如下技术方案予以实现:
氨基酸或氨基酸类似物或其盐在作为提高尿囊素溶解性能的添加剂的应用,所述溶解性能为尿囊素在极性溶剂中的溶解性能。
尽管在一些日化产品中,会存在氨基酸与尿囊素混合的体系,但是并未有披露氨基酸或其类似物或其盐能提高尿囊素在极性溶剂中的溶解性能。发明人意外发现,氨基酸或氨基酸类似物或其盐的存在下,将尿囊素溶解在极性溶剂中能形成稳定的体系后,该体系即在常温状态下,也不会析出尿囊素,因此能够增大了尿囊素在极性溶剂中的溶解性能,得到高尿囊素含量的稳定体系。
优选地,所述极性溶剂优选为水和/或多元醇。
优选地,所述极性溶剂为水和多元醇的混合体系,或多元醇的体系。在纯水体系中,加入氨基酸或其类似物或其盐能提高尿囊素的溶解性能数倍,但在多元醇存在的体系中,这种溶解性能的增加会更明显。
优选地,所述多元醇优选为乙二醇或甘油。
优选地,所述氨基酸优选为赖氨酸或脯氨酸。
优选地,所述氨基酸的类似物优选为肉碱。
本发明中,所述其盐是指氨基酸的盐或氨基酸的类似物的盐。所述盐优选为酸式盐。
优选地,所述氨基酸的盐可以是盐酸盐、二盐酸盐、醋酸盐。
当所述氨基酸为赖氨酸时,氨基酸的盐优选为赖氨酸盐酸盐。
优选地,所述氨基酸的类似物的盐可以是盐酸盐、酒石酸盐、富马酸盐。
上述氨基酸或氨基酸类似物或其盐包括具有该结构的各种手性异构体或消旋体。
由于尿囊素在常温下存在更明显的溶解性能问题。因此,优选地,所述溶解性能为常温下的溶解性能。
优选地,所述氨基酸或氨基酸类似物或其盐的添加量为相对于每1g尿囊素,至少加入0.1g的氨基酸或氨基酸类似物或其盐。
一种高尿囊素含量的常温稳定溶液,所述溶液按重量百分数计,包括如下组分:
尿囊素 0.6~30%;
氨基酸或氨基酸类似物或其盐 0.5~50%;
极性溶剂 余量;
所述极性溶剂为多元醇和/或水。
更优选地,所述高尿囊素含量的常温稳定溶液中,尿囊素的重量百分数为1~30%。
当所述极性溶剂仅仅为水时,优选地,一种高尿囊素含量的常温稳定溶液,所述溶液按重量百分数计,包括如下组分:
尿囊素 0.6~4%;
氨基酸或氨基酸类似物或其盐 0.5~15%;
水 余量。
更优选地,当所述极性溶剂仅仅为水时,所述高尿囊素含量的常温稳定溶液中,尿囊素的重量百分数为1~30%。
上述高尿囊素含量的常温稳定溶液可以有多种方法制备:
作为可以实施的方法之一,可以是将氨基酸或氨基酸类似物或其盐、极性溶剂在常温或加热下搅拌溶解,至形成均匀透明液体,冷却即得所述常温稳定溶液。该方法中,可以是将尿囊素与氨基酸或氨基酸类似物或其盐同时加入极性溶剂中,或者是先将氨基酸或氨基酸类似物或其盐溶于极性溶剂中,再加入尿囊素。且,当所述极性溶剂为水时,优选在常温下进行搅拌溶解。当所述极性溶剂为多元醇时,优选在加热下进行搅拌溶解。
作为可以实施的方法之一,可以是将尿囊素、氨基酸或氨基酸类似物或其盐、多元醇和水混合均匀,减压蒸馏至质量恒定,即得所述常温稳定溶液。
作为可以实施的方法之一,可以是将尿囊素、氨基酸或氨基酸类似物或其盐、多元醇和水混合均匀,冷冻干燥至质量恒定,即得所述常温稳定溶液。
所述高尿囊素含量的常温稳定溶液在作为尿囊素原料中的应用。本发明所述高尿囊素含量的常温稳定溶液可以代替现有的尿囊素原料,用于日化领域、医学领域、农业领域等。并且本发明的尿囊素分散在溶液中,呈液态,更易于实现均匀分散。
一种提高尿囊素在极性溶剂中溶解性能的方法,为将氨基酸或氨基酸类似物或其盐、极性溶剂作为提高尿囊素溶解度的添加剂加入含有尿囊素的极性溶剂体系中。
与现有技术相比,本发明具有如下有益效果:
本发明公开氨基酸或氨基酸类似物或其盐在作为提高尿囊素溶解性能添加剂的应用。通过氨基酸或氨基酸类似物或其盐的加入,可以使高浓度的尿囊素在极性溶剂,尤其是水或多元醇体系中形成常温稳定溶液。这种含有高尿囊素含量的常温稳定溶液可以代替现有的尿囊素原料,用于日化领域、医学领域、农业领域等,并且由于尿囊素分散在溶液中呈液态,更易于实现均匀分散,因此能大大提高尿囊素的应用效率及生物利用度。所述含有高尿囊素含量的常温稳定溶液的制备方法步骤简单、工序耗时短,适合工业生产。
附图说明
图1为实施例1按照减压蒸馏法得到的稳定溶液示意图;
图2为实施例2按照加热法得到的稳定溶液示意图;
图3为实施例3按照加热法得到的稳定溶液示意图;
图4为实施例4按照加热法得到的稳定溶液示意图;
图5为实施例5按照加热法得到的稳定溶液示意图;
图6为实施例8按照冷冻干燥法得到的稳定溶液示意图;
图7为实施例9按照减压蒸馏法得到的稳定溶液示意图;
图8为实施例12按照加热法得到的稳定溶液示意图;
图9为实施例14按照加热法得到的稳定溶液示意图;
图10为实施例15按照加热法得到的稳定溶液示意图;
图11为实施例18制备得到的稳定溶液示意图;
图12为实施例19制备得到的稳定溶液示意图;
图13为实施例20制备得到的稳定溶液示意图;
图14为对比例1制备的溶液未加入氨基酸前的状态示意图;
图15为对比例1制备的溶液加入氨基酸后的状态示意图;
图16为实施例5按照加热法得到的稳定溶液的红外谱图;
图17为实施例8按照冷冻干燥法得到的稳定溶液的红外谱图;
图18为实施例9按照减压蒸馏法得到的稳定溶液的红外谱图;
图19为实施例14按照加热法得到的稳定溶液的红外谱图。
具体实施方式
下面结合具体实施例和对比例对本发明做进一步的详细说明,但本发明并不限于下述实施例。
实施例中,未有特别说明的原料均为常规市售商品。
实施例1~17
实施例1~17的稳定溶液配方如表1、表2、表3所示
表1
表2
表3
按照表1、表2、表3的配方,每个实施例中,采用如下3种方法分别制备常温稳定溶液:
方法一(加热法):将甘油/乙二醇、L-赖氨酸和尿囊素加入圆底烧瓶中,加热至40~110℃,搅拌至形成均匀透明液体,冷却即得所述常温稳定溶液。
方法二(蒸发法):将甘油/乙二醇、L-赖氨酸和尿囊素混合,并加入少量水(约50~100g)直至得到的混合体系呈均匀澄清状态,然后减压蒸馏除去体系中的水,将得到的澄清透明液体,澄清透明液体放入干燥器中,干燥至其重量保持不变,即得所述常温稳定溶液。
方法三(冷冻干燥法):将甘油/乙二醇、L-赖氨酸和尿囊素混合,并加入少量水(约50~100g)直至得到的混合体系呈均匀澄清状态,再转移至冷冻干燥器中进行冷冻干燥,至其重量保持不变,即得所述常温稳定溶液。
实施例1~17采用上述方法均成功制备出常温稳定溶液,溶液呈澄清透明状。如图1-10所示。
从图1-图10可以看出,制备出的稳定溶液澄清透明,说明在添加了氨基酸或氨基酸类似物或其盐后,能提高尿囊素在多元醇体系下的溶解性能。
从图1-5还可以看出,随着赖氨酸的添加量提高,体系的颜色会变得偏黄,这是由于赖氨酸本身溶于极性溶液或水中的液体颜色显黄色。
图15为对应图5所示实施例5样品的红外谱图,从该红外图可以看出,由于在稳定溶液中甘油的含量大,所以大部分情况下覆盖了L-赖氨酸和尿囊素的信号。在大约波数为1405cm-1处为L-赖氨酸的一个信号峰,在大约波数为1170cm-1处,能看到尿囊素的一个特征信号峰,确认体系中存在尿囊素。
图16为对应图6所示实施例8样品的红外谱图,从该红外图可以看出,由于在稳定溶液中乙醇的含量大,所以基本上覆盖了L-赖氨酸和尿囊素的信号。在大约波数为1404cm-1处为L-赖氨酸的一个信号峰,在大约波数为1174.60cm-1处,能看到尿囊素的一个特征信号峰,确认体系中存在尿囊素。
图17为对应图7所示实施例9样品的红外谱图,从该红外图可以看出,虽然在稳定溶液中甘油的含量大,但在2930cm-1处能看到L-脯氨酸的信号,在1727cm-1及1648cm-1处,能看到尿囊素的特征峰,确认体系中存在尿囊素。
图18为对应图9所示实施例14样品的红外谱图,从该红外图可以看出,由于在稳定溶液中甘油的含量大,所以大部分情况下覆盖了L-赖氨酸、肉碱和尿囊素的信号。尿囊素在3500-3300cm-1、1789-1670cm-1的特征峰,均被覆盖。在大约波数为1595cm-1处,能看到肉碱的一个信号峰。在大约波数为1401cm-1处为L-赖氨酸的一个信号峰。
实施例18(尿囊素质量百分比2.18%)
取3.00gL-赖氨酸于烧杯中,加入纯水至100.00g,配成质量百分比为3%的L-赖氨酸水溶液。
取2.00g尿囊素于烧杯中,逐滴加入配制好的3%L-赖氨酸水溶液,搅拌均匀,直至尿囊素白色粉末完全溶解于溶液中。当尿囊素完全溶解时,停止加入L-赖氨酸水溶液。测得加入的3%L-赖氨酸水溶液消耗体积约89.50ml,重量为89.81g,即得到尿囊素质量百分比为2.18%的常温稳定溶液。溶液呈澄清透明状。如图11所示。
需要说明的是,图1~图11的溶液为放置2个月后的溶液,颜色会有变黄的现象。
对比例1
参照实施例18取100g水于烧杯中,加入2.00g尿囊素,搅拌24h,仍呈浑浊状态,可以看到大量尿囊素未溶于水中。如图14所示。然后往其中加入浑浊的溶液中,加入2.8gL-赖氨酸,搅拌2分钟,溶液呈澄清透明状。如图15所示。可以证实,氨基酸的加入明显改善了尿囊素的溶解度。图14和图15的溶液为实验完毕后直接拍摄的溶液,基本不呈无色状。
实施例19:(尿囊素质量百分比2.95%)
取3.75g L-赖氨酸于烧杯中,加入纯水至75.00g,配成质量百分比为5%的L-赖氨酸水溶液。
取2.00g尿囊素于烧杯中,逐滴加入配制好的5%L-赖氨酸水溶液,搅拌均匀,直至尿囊素白色粉末完全溶解于溶液中。当尿囊素完全溶解时,停止加入L-赖氨酸水溶液。测得加入的5%L-赖氨酸水溶液消耗体积约65.50ml,重量为65.69g,即得到尿囊素质量百分比为2.95%的常温稳定溶液。溶液呈澄清透明状。如图12所示。
实施例20:(尿囊素质量百分比3.66%)
取4.20gL-赖氨酸于烧杯中,加入纯水至60.00g,配成质量百分比为7%的L-赖氨酸水溶液。
取2.00g尿囊素于烧杯中,逐滴加入配制好的7%L-赖氨酸水溶液,搅拌均匀,直至尿囊素白色粉末完全溶解于溶液中。当尿囊素完全溶解时,停止加入L-赖氨酸水溶液。测得加入的7%L-赖氨酸水溶液消耗体积约52.00ml,重量为52.63g,即得到尿囊素质量百分比为3.66%的澄清透明溶液。如图13所示。
从图11-图13可以看出,制备出的稳定溶液澄清透明,说明在添加了氨基酸或氨基酸类似物或其盐后,能提高尿囊素在水体系下的溶解性能。
稳定性测试
将上述图1、图5、图6、图7、图9对应的实施例1、实施例5、实施例8、实施例9、实施例14制备的澄清透明溶液,分别与水按99:1,1:99的比例混合,静置24h,观察是否有沉淀析出,结果如表4所示。
表4
从表4看出,本发明的高尿囊素含量的常温稳定溶液十分稳定,在与不同比例的水混合后,仍不会出现沉淀,有较好的应用前景。
以上所述,仅为本发明的具体实施方式,但本发明的保护范围并不局限于此,任何熟悉本技术领域的技术人员在本发明揭露的技术范围内,可轻易想到各种等效的修改或替换,这些修改或替换都应涵盖在本发明的保护范围之内。因此,本发明的保护范围应以权利要求的保护范围为准。
Claims (10)
1.氨基酸或氨基酸类似物或其盐在作为提高尿囊素溶解性能的添加剂的应用,其特征在于,所述溶解性能为尿囊素在极性溶剂中的溶解性能。
2.根据权利要求1所述应用,其特征在于,所述极性溶剂为水和/或多元醇。
3.根据权利要求1所述应用,其特征在于,所述氨基酸为赖氨酸或脯氨酸;所述氨基酸类似物为肉碱。
4.根据权利要求1所述应用,其特征在于,所述溶解性能为常温下的溶解性能。
5.根据权利要求1至4任一项所述应用,其特征在于,所述氨基酸或氨基酸类似物或其盐的添加量为相对于每1g尿囊素,至少加入0.1g的氨基酸或氨基酸类似物或其盐。
6.一种高尿囊素含量的常温稳定溶液,其特征在于,所述常温稳定溶液按重量百分数计,包括如下组分:
尿囊素 0.6~30%;
氨基酸或氨基酸类似物或其盐 0.1~50%;
极性溶剂 余量;
所述极性溶剂为多元醇和/或水。
7.权利要求6所述高尿囊素含量的常温稳定溶液的制备方法,其特征在于,将尿囊素、氨基酸或氨基酸类似物或其盐、极性溶剂在常温或加热下搅拌溶解,至形成均匀透明液体,冷却即得所述常温稳定溶液。
8.权利要求6所述高尿囊素含量的常温稳定溶液的制备方法,其特征在于,将尿囊素、氨基酸或氨基酸类似物或其盐、多元醇和水混合均匀,减压蒸馏至质量恒定,即得所述常温稳定溶液。
9.权利要求6所述高尿囊素含量的常温稳定溶液的制备方法,其特征在于,将尿囊素、氨基酸或氨基酸类似物或其盐、多元醇和水混合均匀,冷冻干燥至质量恒定,即得所述常温稳定溶液。
10.权利要求6所述高尿囊素含量的常温稳定溶液在作为尿囊素原料中的应用。
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US4038287A (en) * | 1975-04-21 | 1977-07-26 | Kawaken Fine Chemicals Co., Ltd. | Compounds of allantoin with basic amino acids |
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