CN108840889A - 一种壳寡糖基化合物的应用及其制备方法 - Google Patents
一种壳寡糖基化合物的应用及其制备方法 Download PDFInfo
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- RQFQJYYMBWVMQG-IXDPLRRUSA-N chitotriose Chemical compound O[C@@H]1[C@@H](N)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](N)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)[C@@H](CO)O1 RQFQJYYMBWVMQG-IXDPLRRUSA-N 0.000 title claims abstract description 152
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- DOUMFZQKYFQNTF-WUTVXBCWSA-N (R)-rosmarinic acid Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-WUTVXBCWSA-N 0.000 claims abstract description 50
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims abstract description 46
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- DOUMFZQKYFQNTF-MRXNPFEDSA-N rosemarinic acid Natural products C([C@H](C(=O)O)OC(=O)C=CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-MRXNPFEDSA-N 0.000 claims abstract description 25
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- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
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Abstract
本发明涉及生物材料技术领域,具体涉及一种壳寡糖基化合物作为生物材料的应用,壳寡糖基化合物具有如式(Ⅰ)所示的结构,R为叶酸、月桂酸、迷迭香酸中的至少一种与其所含羧基相连的支链。以聚合度为1~8的壳寡糖为主链,支链接枝在壳寡糖分子的活泼氨基处,使得壳寡糖基生物材料具备其它糖基生物材料所不具备的稳定性;同时,叶酸、月桂酸、迷迭香酸的接入增大了壳寡糖分子间的位阻,使得壳寡糖分子间不易形成氢键,进一步增强其溶解性。经改性的壳寡糖可作为一种新型的生物材料使用,扩大了以壳寡糖基为主链的生物材料的适用范围,而且原料成本低,工艺简单、产率高。
Description
技术领域
本发明属于生物材料技术领域,具体涉及一种壳寡糖基化合物的应用及其制备方法。
背景技术
生物医用材料(Biomedical Materials)是用来对生物体进行诊断、治疗、修复或替换其病损组织、器官或增进其功能的材料,是研究人工器官和医疗器械的基础,已成为当代材料学科的重要分支,尤其是随着生物技术的蓬勃发展和重大突破,生物医用材料已成为各国科学家竞相进行研究和开发的热点。
糖、蛋白质和核酸是生命攸关的三大生物大分子,其中,糖是存在自然界中的最大的生物量,糖链是自然界中最大的生物信息库,在控制细胞分裂和分化、调节细胞生长和衰老以及维护有机生命体的正常代谢等方面有重要作用。同时,糖还因其具有良好的生物相容性、生物可降解性以及生物活性等而用作生物医用材料。自上个世纪80年代以来,国外形成了甲壳素(Chitin)、壳聚糖(Chitoson,CS)等多糖类生物医用材料的研究热潮,由此促生了糖生物工程的发展,糖生物工程是继基因工程、蛋白质工程之后又一引人注目的生物技术新领域。
研究发现,壳聚糖经水解可制得壳寡糖(CSO),一般由2~20个糖单元组成,分子量≤3200Da。壳寡糖具有壳聚糖无法比拟的优越性,如:它具有壳聚糖所没有的溶解性,壳聚糖只能溶于酸性溶液,而壳寡糖能溶于pH大于10的碱性水溶液;壳寡糖更容易被生物体吸收,而且表现出多重生理活性,具有提高免疫力、消除人体氧负离子自由基、活化机体细胞等功能。目前,已有文献报道将壳寡糖作为生物降解材料、药物控释载体和组织工程材料等方面的应用。但是,在壳寡糖的应用领域,仍面临一些亟待解决的技术难题,如:壳寡糖分子在高浓度及高温条件下容易发生缩合反应,在溶液状态且高于80℃时易被氧化;而且壳寡糖分子之间很容易形成氢键,导致其溶解性差,限制了其作为生物医用材料的应用。
因此,对现有壳寡糖进行改性以制备新型壳寡糖基生物材料,以改善其化学稳定性、提高其溶解性,将具有十分重要的意义。
发明内容
因此,本发明的要解决的技术问题在于克服现有技术中的壳寡糖化学稳定性差、溶解性差的问题,从而提供一种新的壳寡糖基生物材料。
为了解决上述技术问题,本发明采用的技术方案如下:
本发明提供一种壳寡糖基化合物作为生物材料的应用。
可选的,所述壳寡糖基化合物由壳寡糖与叶酸、月桂酸、迷迭香酸中的至少一种反应制得;其中,所述的壳寡糖基化合物具有如式(Ⅰ)结构:
R1、R2、R3中至少一个为叶酸、月桂酸或迷迭香酸的取代位置,其余为H;
n为壳寡糖单元重复数,1≤n≤8。
可选的,上述结构壳寡糖基生物材料,6≤n≤8。
本发明还提供上述的壳寡糖基化合物的制备方法,所述壳寡糖基化合物的制备方法包括以下步骤:
其中,上述R为叶酸、月桂酸、迷迭香酸中的至少一种与其所含羧基相连的支链,R1、R2、R3中至少一个取代位置为取代;
(1)将式(I-1)所述R-COOH加至含二氯亚砜的混合溶剂中,避光反应得到含有式(I-2)所述化合物的反应液;
(2)向步骤(1)所述的反应液中加入壳寡糖的甲基磺酸溶液,得到含有式(I)所述化合物的反应溶液;调节反应溶液pH大于9,过滤,收集滤饼,即得壳寡糖基生物材料;
其中,所述混合溶剂为二氯亚砜-乙醇-水溶液或者二氯亚砜-甲醇-水溶液。
可选的,上述的壳寡糖基化合物的制备方法,壳寡糖:R-COOH:二氯亚砜:甲基磺酸(mol:mol:ml:ml)=1:(1.0~10.0):(220~730):(200~650)。
可选的,上述的壳寡糖基化合物的制备方法,
步骤(1)中,反应温度为20~25℃,反应时间为0.5~1.0小时;
步骤(2)中,反应温度为0~5℃,反应时间为4~5小时。
可选的,上述的壳寡糖基化合物,所述混合溶剂中,二氯亚砜:乙醇:水(ml:ml:ml)=1:(13~15):(4~6);或者,二氯亚砜:甲醇:水(ml:ml:ml)=1:(9~12):(7~10)。
可选的,上述的壳寡糖基化合物的制备方法,还包括所述壳寡糖的制备方法:
将壳聚糖加至盐酸中,75~80℃加热搅拌溶解,调节溶液pH值为4.0~4.7,加入纤维素酶,反应10~15小时,4000~4100r/min离心8~10分钟,上清液以所需分子量的超滤膜分级,所得超滤液经冷冻干燥,得到聚合度为1~8的壳寡糖;
其中,壳聚糖:盐酸:纤维素酶(g:ml:g)=1:(30~50):(0.005~0.01)。
可选的,上述的壳寡糖基化合物的制备方法,所述盐酸的浓度为3~6mol/L;所述冷冻干燥的温度为-45~-20℃。
本发明还提供上述的壳寡糖基化合物在作为荧光分子载体的应用。
本发明的上述技术方案具有以下优点:
1.本发明提供的壳寡糖基化合物作为生物材料的应用,经改性的壳寡糖可作为一种新型的生物材料使用,扩大了以壳寡糖基为主链的生物材料的适用范围。
2.本发明提供的壳寡糖基化合物作为生物材料的应用,该壳寡糖基生物材料以壳寡糖为主链,在壳寡糖的氨基上引入叶酸、月桂酸、迷迭香酸中的至少一种反应制得。
叶酸、月桂酸、迷迭香酸分子本身的稳定较好,而且接枝在壳寡糖分子的活泼氨基处,所得到的壳寡糖基生物材料具备其它糖基生物材料所不具备的稳定性,如在食盐、蔗糖、强酸、重金属离子、高温等环境下,仍能保持其稳定性而不发生降解、氧化等;同时,叶酸、月桂酸、迷迭香酸的介入增大了壳寡糖分子间的位阻,使得壳寡糖分子间不易形成氢键,进一步增强其溶解性。
3.本发明提供的壳寡糖基化合物作为生物材料的应用,迷迭香酸具有较壳寡糖更好的水溶性,经引入迷迭香酸后,材料分子所含羟基比例增加,提升了壳寡糖基生物材料的水溶性。
4.本发明提供的壳寡糖基化合物的制备方法,原料成本低,工艺简单、产率高,通过该方法制备的壳寡糖基生物材料具有良好的生物相容性,而且无毒性,可以代替传统芯片作为荧光分子载体,对于生物体或者组织的检测、诊断等具有重要的意义。
附图说明
为了更清楚地说明本发明具体实施方式或现有技术中的技术方案,下面将对具体实施方式或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图是本发明的一些实施方式,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1是本发明实施例1制备的壳寡糖基化合物的高效液相图谱;
图2是本发明实施例2制备的壳寡糖基化合物的高效液相图谱;
图3是本发明实施例3制备的壳寡糖基化合物的高效液相图谱;
图4是本发明实施例4制备的壳寡糖基化合物的高效液相图谱;
图5是本发明实施例1-4制备的壳寡糖基化合物的红外波谱图。
具体实施方式
下面将结合附图对本发明的技术方案进行清楚、完整地描述,显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。此外,下面所描述的本发明不同实施方式中所涉及的技术特征只要彼此之间未构成冲突就可以相互结合。
本发明实施例所用的试剂等基础化工原料,均可在国内化工产品市场买到,或在有关中间体制备厂定做。
实施例1
本实施例提供一种作为生物材料的壳寡糖基化合物,R1、R3为H取代,R2为迷迭香酸取代,具有如式(Ⅰ)结构:
其中,1≤n≤2。
本实施例提供一种如式(Ⅰ)所示结构的壳寡糖基生物材料的合成路线,包括如下步骤:
(1)壳寡糖的制备
将市售低分子量壳聚糖(脱乙酰度DAC≥85)5.0g加至200ml 4.5mol/L盐酸中,油浴78℃加热搅拌溶解,调节溶液pH值为4.3,加入0.0375g纤维素酶,继续78℃反应13小时,4000r/min下离心9min,上清液以所需分子量的超滤膜分级,所得超滤液在-30℃冷冻干燥,即得壳寡糖。
(2)壳寡糖基生物材料的制备
将0.02mol迷迭香酸加至52.5ml二氯亚砜-乙醇-水溶液中,避光23℃搅拌反应0.7小时;再加入步骤(1)制备的壳寡糖的甲基磺酸混合溶液(0.01mol壳寡糖,2.6ml甲基磺酸),保持温度3℃搅拌反应4小时;然后调节溶液pH值为10,过滤,收集滤饼;
其中,二氯亚砜-乙醇-水溶液中,二氯亚砜2.5ml、乙醇35.0ml、水15.0ml。
(3)提纯
将步骤(2)所得的滤饼加至双蒸水溶解,透析处理,除去反应副产物,所得透析液-45℃冷冻干燥,即得到迷迭香酸接枝的壳寡糖基生物材料。
实施例2
本实施例提供一种作为生物材料的壳寡糖基化合物,R1、R2为H取代,R3为月桂酸取代,具有如式(Ⅰ)结构:
其中,3≤n≤4。
本实施例提供一种如式(Ⅰ)所示结构的壳寡糖基生物材料的合成路线,包括如下步骤:
(1)壳寡糖的制备
将市售低分子量壳聚糖(脱乙酰度DAC≥85)5.0g加至150ml 6mol/L盐酸中,油浴80℃加热搅拌溶解,调节溶液pH值为4.7,加入0.025g纤维素酶,继续80℃反应10小时,4050r/min下离心10min,上清液以所需分子量的超滤膜分级,所得超滤液在-45℃冷冻干燥,即得壳寡糖。
(2)壳寡糖基生物材料的制备
将0.01mol月桂酸加至43.8ml二氯亚砜-乙醇-水溶液中,避光20℃搅拌反应0.5小时;再加入步骤(1)制备的壳寡糖的甲基磺酸混合溶液(0.01mol壳寡糖,2.0ml甲基磺酸),保持温度0℃搅拌反应5小时;然后调节溶液pH值为11,过滤,收集滤饼;
其中,二氯亚砜-乙醇-水溶液中,二氯亚砜2.0ml、乙醇33.0ml、水8.8ml。
(3)提纯
将步骤(2)所得的滤饼加至双蒸水溶解,透析处理,除去反应副产物,所得透析液-30℃冷冻干燥,即得到月桂酸接枝的壳寡糖基生物材料。
实施例3
本实施例提供一种作为生物材料的壳寡糖基化合物,R1、R3为叶酸取代,R2为H取代,具有如式(Ⅰ)结构:
其中,5≤n≤6。
本实施例提供一种如式(Ⅰ)所示结构的壳寡糖基生物材料的合成路线,包括如下步骤:
(1)壳寡糖的制备
将市售低分子量壳聚糖(脱乙酰度DAC≥85)5.0g加至250ml 3mol/L盐酸中,油浴75℃加热搅拌溶解,调节溶液pH值为4.0,加入0.05g纤维素酶,继续75℃反应15小时,4100r/min下离心8min,上清液以所需分子量的超滤膜分级,所得超滤液在-20℃冷冻干燥,即得壳寡糖。
(2)壳寡糖基生物材料的制备
将0.02mol叶酸加至81.0ml二氯亚砜-乙醇-水溶液中,避光25℃搅拌反应1.0小时;再加入步骤(1)制备的壳寡糖的甲基磺酸溶液(0.01mol壳寡糖,4.0ml甲基磺酸),保持温度5℃搅拌反应4.5小时;然后调节溶液pH值为9.1,过滤,收集滤饼;
其中,二氯亚砜-乙醇-水溶液中,二氯亚砜4.5ml、乙醇58.5ml、水22.5ml。
(3)提纯
将步骤(2)所得的粗品加至双蒸水溶解,透析处理,除去反应副产物,所得透析液-20℃冷冻干燥,即得到叶酸接枝的壳寡糖基生物材料。
实施例4
本实施例提供一种作为生物材料的壳寡糖基化合物,R1为迷迭香酸取代,R2为H取代,R3为月桂酸取代,具有如式(Ⅰ)结构:
其中,7≤n≤8。
本实施例提供一种如式(Ⅰ)所示结构的壳寡糖基生物材料的合成路线,包括如下步骤:
(1)壳寡糖的制备
将市售低分子量壳聚糖(脱乙酰度DAC≥85)5.0g加至200ml 4mol/L盐酸中,油浴75℃加热搅拌溶解,调节溶液pH值为4.0,加入0.025g纤维素酶,继续75℃反应10小时,4000r/min下离心8min,上清液以所需分子量的超滤膜分级,所得超滤液在-45℃冷冻干燥,即得壳寡糖。
(2)壳寡糖基生物材料的制备
将0.01mol迷迭香酸、0.01mol月桂酸加至153.3ml二氯亚砜-甲醇-水溶液中,避光20℃搅拌反应1.0小时;再加入步骤(1)制备的壳寡糖的甲基磺酸混合溶液(0.01mol壳寡糖,6.5ml甲基磺酸),保持温度0℃搅拌反应5小时;然后调节溶液pH值为11,过滤,收集滤饼;
其中,二氯亚砜-甲醇-水溶液中,二氯亚砜7.3ml、甲醇73.0ml、水73.0ml。
(3)提纯
将步骤(2)所得的滤饼加至双蒸水溶解,透析处理,除去反应副产物,所得透析液-30℃冷冻干燥,即得到迷迭香酸和月桂酸接枝的壳寡糖基生物材料。
实施例5
本实施例提供如式(Ⅰ)所示结构的壳寡糖基生物材料的合成路线,与实施例4的步骤相比,其不同在于:
步骤(2)中,混合溶剂采用二氯亚砜-甲醇-水体系,146.0ml;其中,二氯亚砜7.3ml、甲醇87.6ml、水51.1ml。
实施例6
本实施例提供如式(Ⅰ)所示结构的壳寡糖基生物材料的合成路线,与实施例1的步骤相比,其不同在于:
步骤(2)中,混合溶剂采用二氯亚砜-甲醇-水体系,131.5ml;其中,二氯亚砜7.3ml、甲醇65.7ml、水58.5ml。
测试例1
本发明采用纤维素酶水解壳聚糖制备壳寡糖,然后接枝叶酸、月桂酸、迷迭香酸中的至少一种,得到新型壳寡糖基生物材料,对所制备的壳寡糖基生物材料依次进行高效液相色谱(HPLC)分析、质谱分析、红外光谱进行。
1.检测条件
1.1高效液相色谱(HPLC)分析
高效液相色谱分析条件:色谱柱Shodex NH2P 50 4E(4.6mm×250nm);流动相:A相为水、B相为乙腈;洗脱条件:0~5min 75%B,5~40min 75%B~50%B,40~50min50%B,50~60min 50%B~75%B;检测器:蒸发光散射检测器,检测器温度50℃;柱温:35℃;流速:0.5ml/min;样品浓度:5mg/ml;进样量:20μl。
1.2红外光谱测定
将粉末样品通过KBr压片法制成薄片,采用红外光谱仪测定,分辨率4cm-1,扫描32次。
2.检测结果
实施例1-4制备的壳寡糖基生物材料的高效液相图谱分别如图1-图4所示,通过该制备得到的壳寡糖基生物材料纯度较高。
实施例1-4制备的壳寡糖基生物材料的红外波谱如图5所示,结果显示,在4000~400cm-1红外波数范围内,壳寡糖基生物材料的红外波谱相似,都具有糖类物质所具有的典型红外特征吸收峰。在3300cm-1左右的强吸收为糖环中O-H及N-H的伸缩振动吸收峰;2800cm-1左右为糖环中C-H的伸缩振动吸收峰;1600cm-1左右为N-H的弯曲振动峰;1380cm-1左右为糖环中C-H的弯曲振动峰;1150cm-1左右为环内醚C-O-C的伸缩振动峰;1070cm-1和1030cm-1左右,分别为二级醇羟基和一级醇羟基中C-O的伸缩振动峰;890cm-1左右为糖环的伸缩振动峰。
测试例2
本发明采用纤维素酶水解壳聚糖制备壳寡糖,然后接枝叶酸、月桂酸、迷迭香酸中的至少一种,得到新型壳寡糖基生物材料,对所制备的壳寡糖基生物材料从溶解度、温度、pH等方面验证其化学稳定性。
1.壳寡糖基生物材料的溶解性
1.1壳寡糖、实施例1-4制备的壳寡糖基生物材料溶解性比较
将市售低分子量壳寡糖(脱乙酰度DAC≥85)以及由实施例1-4制备的壳寡糖基生物材料分别加至100ml去离子水、100ml盐酸(pH=3)、100ml NaOH溶液(pH=13)中,观察它们不同加入量在85℃的溶解情况,详见表1。
表1壳寡糖、实施例1-4制备的壳寡糖基生物材料水溶性比较
由表1得知,由实施例1-4提供的方法制备的壳寡糖基生物材料比壳寡糖具有更好的溶解性,这说明了在壳寡糖分子上接枝叶酸、月桂酸、迷迭香酸中的至少一种,能够改善壳寡糖的溶解性;而且,经叶酸、月桂酸、迷迭香酸中的至少一种接枝后,壳寡糖基生物材料在酸液、碱液中的溶解性也大大提高,扩展了壳寡糖基生物材料的适用范围。
1.2壳寡糖基生物材料的化学稳定性
1.2.1壳寡糖基生物材料高温稳定性
将市售低分子量壳聚糖(脱乙酰度DAC≥85,HPLC纯度≥99.95%)以及由实施例1-4制备的壳寡糖基生物材料(HPLC纯度≥99.95%)分别加至100ml去离子水中,分别加热至37℃、65℃、90℃,在不同时间段检测其液相纯度,详见表2。
表2壳聚糖、实施例1-4制备的壳寡糖基生物材料高温稳定性比较
由表1得知,由实施例1-4提供的方法制备的壳寡糖基生物材料比壳寡糖具有更好的稳定性,在高温下基本不会发生缩合、氧化等化学反应,这说明了在壳寡糖分子上接枝叶酸、月桂酸、迷迭香酸中的至少一种后,其稳定性均得到提高,适合作为生物材料使用。
1.2.2壳寡糖基生物材料酸碱稳定性
将市售低分子量壳聚糖(脱乙酰度DAC≥85,HPLC纯度≥99.95%)以及由实施例1-4制备的壳寡糖基生物材料(HPLC纯度≥99.95%)分别加至盐酸(pH=3)、NaOH溶液(pH=11)中,分别加在65℃下加热0.5小时,检测其液相纯度,详见表3。
表3壳寡糖、实施例1-4制备的壳寡糖基生物材料酸碱稳定性比较
由表1得知,由实施例1-4提供的方法制备的壳寡糖基生物材料在强酸和强碱环境下比壳寡糖具有更好的稳定性,这说明了在壳寡糖分子上接枝叶酸、月桂酸、迷迭香酸中的至少一种后,其酸碱稳定性均得到提高,适合作为生物材料使用。
测试例3
对实施例1-4制备的壳寡糖基生物材料进行细胞毒性检测,如表4所示:
表4实施例1-4制备的壳寡糖基生物材料细胞毒性测试
由表1得知,由实施例1-4提供的方法制备的壳寡糖基生物材料无毒、无刺激、生物相容性好且满足临床使用。
显然,上述实施例仅仅是为清楚地说明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (10)
1.一种壳寡糖基化合物作为生物材料的应用。
2.根据权利要求1所述的壳寡糖基化合物作为生物材料的应用,其特征在于,所述壳寡糖基化合物由壳寡糖与叶酸、月桂酸、迷迭香酸中的至少一种反应制得;其中,所述的壳寡糖基化合物具有如式(Ⅰ)结构:
R1、R2、R3中至少一个为叶酸、月桂酸或迷迭香酸的取代位置,其余为H;
n为壳寡糖单元重复数,1≤n≤8。
3.根据权利要求2所述的壳寡糖基化合物作为生物材料的应用,其特征在于,7≤n≤8。
4.一种如权利要求1-3任一所述的壳寡糖基化合物的制备方法,其特征在于,所述壳寡糖化合物的合成路线包括以下步骤:
其中,上述R为叶酸、月桂酸、迷迭香酸中的至少一种与其所含羧基相连的支链,R1、R2、R3中至少一个取代位置为取代;
(1)将式(I-1)所述R-COOH加至含二氯亚砜的混合溶剂中,避光反应得到含有式(I-2)所述化合物的反应液;
(2)向步骤(1)所述的反应液中加入壳寡糖的甲基磺酸溶液,得到含有式(I)所述化合物的反应溶液;调节反应溶液pH大于9,过滤,收集滤饼,即得壳寡糖基生物材料;
其中,所述混合溶剂为二氯亚砜-乙醇-水溶液或者二氯亚砜-甲醇-水溶液。
5.根据权利要求4所述的壳寡糖基化合物的制备方法,其特征在于,壳寡糖:R-COOH:二氯亚砜:甲基磺酸(mol:mol:ml:ml)=1:(1.0~10.0):(220~730):(200~650)。
6.根据权利要求4或5所述的壳寡糖基化合物的制备方法,其特征在于,步骤(1)中,反应温度为20~25℃,反应时间为0.5~1.0小时;
步骤(2)中,反应温度为0~5℃,反应时间为4~5小时。
7.根据权利要求4-6任一所述的壳寡糖基化合物的制备方法,其特征在于,所述混合溶剂中,二氯亚砜:乙醇:水(ml:ml:ml)=1:(13~15):(4~6);或者,二氯亚砜:甲醇:水(ml:ml:ml)=1:(9~12):(7~10)。
8.根据权利要求4-7任一所述的壳寡糖基化合物的制备方法,还包括所述壳寡糖的制备方法:
将壳聚糖加至盐酸中,75~80℃加热搅拌溶解,调节溶液pH值为4.0~4.7,加入纤维素酶,反应10~15小时,4000~4100r/min离心8~10分钟,上清液以所需分子量的超滤膜分级,所得超滤液经冷冻干燥,得到聚合度为1~8的壳寡糖;
其中,壳聚糖:盐酸:纤维素酶(g:ml:g)=1:(30~50):(0.005~0.01)。
9.根据权利要求8所述的壳寡糖基化合物的制备方法,其特征在于,所述盐酸的浓度为3~6mol/L;所述冷冻干燥的温度为-45~-20℃。
10.一种如权利要求1-3任一所述的壳寡糖基化合物在作为荧光分子载体的应用。
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