WO2019011061A1 - 一种新型水溶性天然多糖抗菌材料及其制备方法 - Google Patents

一种新型水溶性天然多糖抗菌材料及其制备方法 Download PDF

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WO2019011061A1
WO2019011061A1 PCT/CN2018/088173 CN2018088173W WO2019011061A1 WO 2019011061 A1 WO2019011061 A1 WO 2019011061A1 CN 2018088173 W CN2018088173 W CN 2018088173W WO 2019011061 A1 WO2019011061 A1 WO 2019011061A1
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chitosan
reaction
natural polysaccharide
antibacterial material
solution
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PCT/CN2018/088173
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French (fr)
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牛忠伟
蒋士冬
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中国科学院理化技术研究所
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Priority to JP2020522768A priority Critical patent/JP2020527643A/ja
Priority to US16/629,881 priority patent/US20200181292A1/en
Publication of WO2019011061A1 publication Critical patent/WO2019011061A1/zh

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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
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
    • C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
    • C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom

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  • the invention relates to the field of chitosan preparation, in particular to a novel water-soluble natural polysaccharide antibacterial material and a preparation method thereof.
  • Chitosan whose chemical name is polyglucosamine (1-4)-2-amino-BD glucose, which is obtained from the deacetylation of chitin contained in the shell of crustaceans such as shrimp and crab and the cell wall of fungi.
  • Chitosan has excellent bio-affinity and biodegradability, and is easily made into various derivatives. Due to its extremely rich source, it can be dissolved in hydrochloric acid, acetic acid and other organic acids, and has been widely used in industrial and pharmaceutical fields. Chitosan has become one of the research hotspots in the development of natural antibacterial agents in recent years due to its biodegradability, biocompatibility, biological non-toxicity and antibacterial activity.
  • chitosan due to the large amount of hydrogen bonds in the intramolecular and intermolecular molecules of chitosan, high crystallinity, poorly soluble in water, and only soluble in some dilute acid solutions, chitosan has low antibacterial activity compared to conventional antibacterial agents. Thus, the promotion and application of chitosan as an antibacterial agent are greatly limited.
  • chitosan In order to increase the water solubility of chitosan, various methods have been adopted. For example, the degree of deacetylation of chitosan is controlled to be between 50 and 60%, chitosan is prepared into various inorganic or organic acid salts, and chitosan is chemically modified to obtain water-soluble chitosan. Or a water soluble derivative. Although these methods have solved the problem of water solubility of chitosan well, the antibacterial properties have not been significantly improved.
  • the chitosan molecule contains a reactive hydroxyl group and an amino group, and can be subjected to reaction conditions such as acylation, carboxylation, etherification, NH 2 alkylation, esterification, hydrolysis, etc.
  • Sulfhydryl is the most positively charged bioactive organic base found in nature. It can be protonated under physiological pH and can form positively charged groups under neutral, acidic and basic conditions. Sulfhydryl compounds are widely found in natural products, have strong solubility, and are highly alkaline and positively charged.
  • the thiol group has anti-inflammatory, antihypertensive, hypolipidemic, antiviral, anti-tumor and other biological activities, and has strong alkalinity, strong stability, good biological activity, and easy to form hydrogen chains, thereby having good antibacterial activity. Performance, is widely used in medicine, agriculture, construction, clothing, chemical and other fields.
  • the sulfhydryl group is in a completely protonated state under normal conditions and maintains its positive polarity [Wei Changmei, Synthesis and Crystal Structure of Mercapto Compounds, PhD Thesis, 2004.].
  • the thiol group can act on the receptor and the ligand through electrostatic or hydrogen bonding, and thus can play a very good drug role.
  • the thiol compound is mainly used as an antihypertensive drug, a hypoglycemic agent and an antiviral drug.
  • the amino group on chitosan has high reactivity, so the thiolation modification of chitosan by amino group gives it similar properties to terpenoids, thereby improving the antibacterial and antibacterial properties of chitosan. Hu et al.
  • Xiao et al. used arginine as a thiolation reagent, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC ⁇ HCl) and N-hydroxysuccinyl.
  • Imine (NHS) is used as a catalyst to react arginine with chitosan in 2-(N-morpholino)ethanesulfonic acid (MES) buffer at room temperature, and thiolated chitosan is also obtained [ Xiao B., et.al., Carbohyd. Polym. 2011, 83, 144.].
  • Leucine, isoleucine, lysine and arginine are all essential amino acids.
  • the carboxyl groups contained in these three kinds of amino acids have certain chemical activities and can react with amino groups on chitosan molecules, and are suitable for functional modification of chitosan.
  • a first object of the present invention is to provide a novel water-soluble natural polysaccharide antibacterial material.
  • the molecular structure formula of the natural polysaccharide antibacterial material is as shown in Formula 1:
  • R 1 is:
  • R 2 is:
  • x, y, and n are natural numbers, 0 ⁇ x ⁇ 10 7 , 0 ⁇ y ⁇ 10 7 , and 10 2 ⁇ n ⁇ 10 7 .
  • novel water-soluble natural polysaccharide antibacterial material comprises amino acid and sulfhydryl group, improves the antibacterial effect and application range of chitosan derivative, and is compared with chitosan monoterpene or biguanide hydrochloride derivative. Reduces cytotoxicity and increases its biosafety.
  • Another object of the present invention is to provide a process for preparing the above novel water-soluble natural polysaccharide antibacterial material.
  • step 3 adding an amino acid activation solution to the reaction system of step 2) to carry out an amidation reaction;
  • reaction solution After filtering the reaction solution, it is dialyzed with deionized water and subjected to microwave vacuum drying treatment to obtain a novel water-soluble natural polysaccharide antibacterial material. Microwave vacuum drying technology, low energy consumption and high efficiency.
  • the chitosan has a number average molecular weight of 10 2 -10 7 and a degree of deacetylation of 50-100% in the step 1); preferably, the dilute acid is hydrochloric acid or acetic acid, and the concentration of the acid is 0- 0.5 mol/L; the concentration of the dilute aqueous acid solution of the chitosan is 0.001-0.1 g/mL.
  • the dissolution conditions in step 1) are: constant temperature stirring between 60-110 °C.
  • the molar ratio of the monocyanoamine or dicyandiamide to chitosan in step 2) is from 0.5 to 5:1; and the reaction condition is: constant stirring between 60-110 ° C for 6-48 hours.
  • the amino acid activation solution is obtained by the following method:
  • the concentration of the 2-(N-morpholino)ethanesulfonic acid buffer is 30 mmol/L, and the pH is 5.0 ⁇ 0.5;
  • the amino acid is leucine, isoleucine or lysine.
  • the molar ratio of chitosan to amino acid is from 1 to 50:1; and the amidation temperature in step 3) is from 0 to 35 °C.
  • step 5 during the deionized water dialysis process, the water is changed every 5-10 hours, and the water is changed 6-8 times.
  • the present invention by mechanically grinding the cellulose powder and the solid polymer abrasive material, a new cellulose material having a microscopic morphology which has not been previously found is obtained.
  • the sheet-like cellulose material has a function of blocking the transmission of ultraviolet rays.
  • Example 1 is an infrared spectrum of a raw material chitosan and a novel water-soluble natural polysaccharide antibacterial material prepared in Example 1 of the present invention.
  • Example 2 is a photograph showing the results of an antibacterial property test of a novel water-soluble natural polysaccharide antibacterial material prepared in Example 1 of the present invention by using a method of testing the antibacterial property of GB15979-2002 "Sanitary Standard for Disposable Sanitary Products” by the method of pouring plate for Staphylococcus aureus.
  • Example 3 is a comparison test result of toxicity of a novel water-soluble natural polysaccharide antibacterial material prepared in Example 1 of the present invention and a commercially available quaternary ammonium salt chitosan derivative antibacterial material on ME3T3-E1 cells.
  • x, y, and n are natural numbers, 0 ⁇ x ⁇ 10 7 , 0 ⁇ y ⁇ 10 7 , and 10 2 ⁇ n ⁇ 10 7 .
  • chitosan 0.5 g was added to 100 ml of dilute hydrochloric acid at a concentration of 0.1 mol/L, and mechanically stirred for 60 hours under an oil bath at 60 ° C, so that the chitosan was completely dissolved, thereby obtaining a chitosan concentration of 0.005 g/ a uniform solution of mL; heat the oil bath to 110 ° C, add 1.3 g of dicyandiamide to the chitosan solution, the molar ratio of dicyandiamide to chitosan is 5:1, and keep stirring at constant temperature for 6 hours; The reaction solution was cooled to room temperature, and then lysine, N-hydroxysuccinimide (NHS) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide were activated at room temperature for 2 hours.
  • NHS N-hydroxysuccinimide
  • Fig. 1 is a view showing the infrared spectrum of the raw material chitosan and the novel water-soluble natural polysaccharide antibacterial material prepared in Example 1 of the present invention.
  • the black chromatographic line is the raw material chitosan
  • the red line is the new water-soluble natural polysaccharide antibacterial material
  • the broad peak of the raw chitosan at 3438 cm -1 corresponds to -
  • the stretching and vibration of NH 2 and -OH are red-shifted and widened at the peak position after the modification.
  • the broadening of the peak at this position also indicates that these -NH 2 and -OH have different intramolecular and intermolecular hydrogen bonds, and the difference in peak width reflects the strength of the hydrogen bond.
  • FIG. 2 is a photograph showing the results of antibacterial performance test of the novel water-soluble natural polysaccharide antibacterial material prepared according to Example 1 of the present invention in accordance with GB15979-2002 "Sanitary Standard for Disposable Hygiene Products" in the method of pouring plate for Staphylococcus aureus, from left to right.
  • It is a new water-soluble natural polysaccharide antibacterial material (dissolved in neutral deionized water) prepared in this example at a concentration of 0.5 mg/ml, 0.25 mg/ml, 0.125 mg/ml, and a blank control group (without adding any antibacterial agent).
  • the antibacterial test results were incubated for 36 hours in a constant temperature and humidity incubator at 37 °C. The results show that the novel water-soluble natural polysaccharide antibacterial material prepared in the present embodiment has good inhibition performance against Staphylococcus aureus.
  • Example 3 is a comparison test result of toxicity of a novel water-soluble natural polysaccharide antibacterial material prepared in Example 1 of the present invention and a commercially available quaternary ammonium salt chitosan derivative antibacterial material on ME3T3-E1 cells.
  • the data test results show that the novel water-soluble natural polysaccharide antibacterial material has less cytotoxicity and better cytotoxicity than the commercially available quaternary ammonium salt chitosan derivative antibacterial material.
  • chitosan was added to 100 ml of dilute hydrochloric acid having a concentration of 0.15 mol/L, and mechanically stirred under an oil bath condition of 60 ° C for one hour to completely dissolve the chitosan, thereby obtaining a chitosan concentration of 0.02 g / a uniform solution of mL; heat the oil bath to 100 ° C, add 2.08 g of dicyandiamide to the chitosan oil bath system, the molar ratio of dicyandiamide to chitosan is 2:1, 100 ° C oil bath Stir at constant temperature for 12 hours; then the reaction solution in the oil bath was cooled to room temperature, and activated in an ice-water mixed bath for 3 hours of isoleucine, N-hydroxysuccinimide (NHS) and 1-(3-dimethyl) A mixed solution of aminopropyl)-3-ethylcarbodiimide hydrochloride (EDC ⁇ HCl) (solvent is a buffer
  • chitosan 5.0 g was added to 100 ml of dilute hydrochloric acid at a concentration of 0.15 mol/L, and mechanically stirred under an oil bath condition of 60 ° C for one hour to completely dissolve the chitosan, thereby obtaining a chitosan concentration of 0.05 g/ a uniform solution of mL; the oil bath is heated to 80 ° C, 3.91 g of monocyanamide is added to the aqueous chitosan system, the molar ratio of monocyanamide to chitosan is 3:1, and the reaction is maintained at 80 ° C for 24 hours; The reaction solution in the oil bath was cooled to room temperature, and lysine, N-hydroxysuccinimide (NHS) and 1-(3-dimethylaminopropyl)-3-ethyl carbon were activated at room temperature for 2 hours.
  • NPS N-hydroxysuccinimide
  • chitosan 7.0 g was added to 100 ml of dilute hydrochloric acid at a concentration of 0.3 mol/L, and mechanically stirred under an oil bath at 70 ° C for two hours to completely dissolve the chitosan, thereby obtaining a chitosan concentration of 0.07 g/mL.
  • a mixed solution of an acid salt (EDC ⁇ HCl) (solvent is a buffer solution of 2-(N-morpholino)ethanesulfonic acid (MES) at a concentration of 30 mmol/L, a pH of about 5.0) 20 ml is added to the above reaction solution.
  • the reaction was continuously stirred at room temperature for 24 hours, wherein the molar ratio of chitosan, leucine, NHS and EDC was 5:1:4:4; the reaction solution was filtered and placed in a dialysis bag, and the ends of the dialysis bag were tightened. It is placed in deionized water for dialysis treatment, and the water is changed every four hours. After changing the water for eight times, the dialysate is placed in a microwave vacuum dryer to obtain the new water-soluble. Natural polysaccharide antibacterial material.
  • chitosan 10 g was added to 100 ml of dilute hydrochloric acid having a concentration of 0.5 mol/L, and mechanically stirred under an oil bath condition of 60 ° C for two hours to completely dissolve the chitosan, thereby obtaining a chitosan concentration of 0.1 g/ A uniform solution of mL; 2.61 g of dicyandiamide was added to the chitosan aqueous solution at a temperature of 60 ° C in an oil bath, the molar ratio of dicyandiamide to chitosan was 0.5:1, and the reaction was maintained at 60 ° C for 48 hours.

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Abstract

本发明公开了一种新型水溶性天然多糖抗菌材料。所述新型水溶性天然多糖抗菌材料，其分子上既带有胍基又带有氨基酸基团，在提高壳聚糖抗菌性能的同时，兼顾了其生物安全性，细胞毒性小，是一种绿色抗菌产品。本发明还公开了一种制备上述材料的方法，包括以下步骤：1)将壳聚糖溶解到稀酸溶液中，得到壳聚糖的稀酸水溶液；2)向步骤1)所得壳聚糖的稀酸水溶液中加入单氰胺或双氰胺，进行反应；3)将氨基酸活化溶液加入步骤2)的反应体系中，进行酰胺化；4)加入盐酸羟胺终止反应；5)反应液过滤后用去离子水透析，进行微波真空干燥处理，即得新型水溶性天然多糖抗菌材料。该方法可在反应釜内一次反应制得，所用主要原料为来源丰富价格便宜，适合工业化生产。

Description

一种新型水溶性天然多糖抗菌材料及其制备方法 技术领域
本发明涉及壳聚糖制备领域，具体涉及一种新型水溶性天然多糖抗菌材料及其制备方法。
背景技术
壳聚糖，其化学名称为聚葡萄糖胺(1-4)-2-氨基-B-D葡萄糖，它是虾和蟹等甲壳类动物的壳及真菌细胞壁所含的甲壳素的脱乙酰后得到的一种天然碱性多糖。壳聚糖具有优良的生物亲和性和生物可降解性，容易制成各种衍生物。因其来源极其丰富，能溶解在盐酸、醋酸和其它有机酸中，已被广泛应用于工业和医药领域。壳聚糖由于具有生物可降解性、生物相容性、生物无毒性和抗菌活性等特点，使其成为近年来天然抗菌剂开发的研究热点之一。但是，由于壳聚糖分子内和分子间存在大量的氢键、结晶度高、难溶于水、只能溶解于某些稀酸溶液，导致壳聚糖与传统的抗菌剂相比抗菌活性低，从而极大地限制了壳聚糖作为抗菌剂的推广和应用。
为了提高壳聚糖的水溶性，人们采取了多种方法。比如，控制壳聚糖的脱乙酰度在50-60％之间、将壳聚糖制备成各种无机酸或有机酸盐、对壳聚糖进行化学改性，均可以得到水溶性壳聚糖或水溶性衍生物。这些方法虽然很好地解决了壳聚糖水溶性问题，但抗菌性能却未有明显提高。壳聚糖分子上含有可反应的羟基和氨基，可通过控制与羟基或氨基的反应条件，进行如酰基化、羧基化、醚化、NH 2烷基化、酯化、水解等反应[J.Adv.Drug.Deliv.Rev.，2001，50，591.]，引入其他基团制成系列水溶性壳聚糖衍生物，从而改变其物理化学性能，赋予壳聚糖更多的特定功能，以适应更多领域的需要，进一步拓宽壳聚糖的适用范围。
胍基是目前自然界发现的正电性最强的生物活性有机碱，其在生理pH介质下能够质子化，在中性、酸性和碱性条件下均能形成带正电的基团。胍基化合物广泛存在于天然产物中，溶解性强，有很强的碱性和正电性。胍基基团具有抗炎症、降压降血脂、抗病毒、抗肿瘤等生物活性，同时具有强碱性、强稳定性、较好的生物活性，且易于形成氢链，从而具有很好的抗菌性能，被广泛应用于医药、农业、建筑、服装、化工等领域。胍基在一般条件下都处于完全质子化状态，保持正电性[韦长梅，胍基化合物的合成与晶体结 构研究，博士学位论文，2004.]。胍基能通过静电或氢键作用于受体和配体，因而可以起到很好的药物作用，胍基化合物用作药物主要有抗高血压药物、降血糖药和抗病毒药三种。而壳聚糖上的氨基具有较高的反应活性，因此通过氨基对壳聚糖进行胍基化改性赋予其与胍类化合物类似的性能，进而提高壳聚糖的抑菌抗菌性能。Hu等将三氧化硫脲与壳聚糖反应得到胍基壳聚糖亚硫酸氢盐[Hu Y.，et.al.，Carbohyd.Polym.，2007，67，66.]。Sun等以三聚磷酸钠为交联剂，聚六亚甲基胍磷酸盐为胍化试剂合成胍基化壳聚糖[Bioresour.Technol.，2010，101，5693.]。Zhai等人以单腈氨为胍基化试剂跟壳聚糖反应，得到了单胍壳聚糖[Zhai X.，et.al.，J.Appl.Polym.Sci.，2011，121，3569.]。
另外，Xiao等人以精氨酸为胍基化试剂，以1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC·HCl)与N-羟基琥珀酰亚胺(NHS)作为催化剂，让精氨酸与壳聚糖在2-(N-吗啉代)乙烷磺酸(MES)缓冲液中常温下反应，同样得到了胍基化壳聚糖[Xiao B.，et.al.，Carbohyd.Polym.2011，83，144.]。亮氨酸、异亮氨酸、赖氨酸与精氨酸类似，均是人体必需氨基酸。这三类氨基酸所含羧基均具有一定的化学活性，能与壳聚糖分子上的氨基反应，适合用于壳聚糖的功能化改性。
发明内容
本发明的第一个目的在于提供一种新型水溶性天然多糖抗菌材料。
所述天然多糖抗菌材料的分子结构式如式1所示：
Figure PCTCN2018088173-appb-000001
式1
R 1为：
Figure PCTCN2018088173-appb-000002
R 2为：
Figure PCTCN2018088173-appb-000003
Figure PCTCN2018088173-appb-000004
其中，x、y、n为自然数，0＜x≤10 7，0＜y≤10 7，10 2≤n≤10 7。
本发明所提供的新型水溶性天然多糖抗菌材料，同时包含氨基酸和胍基，提高了壳聚糖衍生物抑菌效果和应用范围的同时，相对于壳聚糖单胍或双胍盐酸盐衍生物降低了细胞毒性，提高了其生物安全性。
本发明的另一个目的在于提供一种制备上述新型水溶性天然多糖抗菌材料的方法。
为达到以上目的，本发明采用以下技术方案：
包括如下步骤：
1)将壳聚糖溶解到稀酸溶液中，得到壳聚糖的稀酸水溶液；
2)向步骤1)所得壳聚糖的稀酸水溶液中加入单氰胺或双氰胺，进行反应；
3)将氨基酸活化溶液加入步骤2)的反应体系中，进行酰胺化反应；
4)加入盐酸羟胺终止反应；
5)反应液过滤后用去离子水透析，进行微波真空干燥处理，即得新型水溶性天然多糖抗菌材料。采用微波真空干燥技术，能耗低，效率高。
优选地，步骤1)中所述壳聚糖数均分子量为10 2-10 7，脱乙酰度为50-100％；优选地，所述的稀酸为盐酸或醋酸，酸的浓度为0-0.5mol/L；所述壳聚糖的稀酸水溶液的浓度为0.001-0.1g/mL。
优选地，步骤1)中所述溶解条件为：60-110℃之间恒温搅拌。
优选地，步骤2)中所述单氰胺或双氰胺与壳聚糖的摩尔比为0.5-5∶1；反应条件为：60-110℃之间恒温搅拌6-48小时。
优选地，步骤3)中，所述氨基酸活化溶液通过以下方法得到：
氨基酸、N-羟基琥珀酰亚胺和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐溶解于2-(N-吗啉代)乙烷磺酸缓冲液中，在0-35℃之间恒温搅拌活化0.5-3小时；
所述2-(N-吗啉代)乙烷磺酸缓冲液的浓度为30mmol/L，pH值为5.0±0.5；
其中，1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐与氨基酸的摩尔比为0.5-5∶1，N-羟基琥珀酰亚胺与1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐的摩尔比为1∶1。
优选地，所述氨基酸为亮氨酸、异亮氨酸或赖氨酸。
优选地，壳聚糖与氨基酸的摩尔比为1-50∶1；步骤3)中酰胺化反应温度为0-35℃。
优选地，步骤5)中，去离子水透析过程中，每5-10小时换水一次，换水6-8次。
本发明的有益效果如下：
本发明通过将纤维素粉末和固态高分子研磨材料经过机械研磨，得到了以前没有发现的微观形貌为片状的纤维素新材料。所述片状纤维素材料具有阻断紫外线透过的功能。
附图说明
下面结合附图对本发明的具体实施方式作进一步详细的说明。
图1为原料壳聚糖和本发明实施例1制备的新型水溶性天然多糖抗菌材料的红外谱图。
图2为本发明实施例1制备的新型水溶性天然多糖抗菌材料采用GB15979-2002《一次性卫生用品卫生标准》浇板法检测抗菌性能的方法对金色葡萄球菌进行抗菌性能测试的结果照片。
图3为本发明实施例1制备的新型水溶性天然多糖抗菌材料和市售季铵盐壳聚糖衍生物抗菌材料对ME3T3-E1细胞的毒性对比测试结果。
具体实施方式
下面通过实施例对本发明进行具体描述，有必要在此指出的是本实施例只用于对本发明进行进一步说明，不能理解为对本发明保护范围的限制，该领域的技术熟练人员可以根据以上发明的内容做出一些非本质的改进和调整。
本发明所述的反应如下所示：
Figure PCTCN2018088173-appb-000005
其中R 1为
Figure PCTCN2018088173-appb-000006
R 2为
Figure PCTCN2018088173-appb-000007
Figure PCTCN2018088173-appb-000008
其中，x、y、n为自然数，0＜x≤10 7，0＜y≤10 7，10 2≤n≤10 7。
实施例1：
将0.5克壳聚糖加入到100毫升浓度为0.1mol/L的稀盐酸中，60℃油浴条件下，机械搅拌半小时，以便壳聚糖溶解完全，从而得到壳聚糖浓度为0.005g/mL的均匀溶液；将油浴升温至110℃，向壳聚糖溶液中一次性加入1.3克双氰胺，双氰胺与壳聚糖的摩尔比为5∶1，保持恒温搅拌6小时；将反应液降温至室温，然后将在室温下活化2小时的赖氨酸、N-羟基琥珀酰亚胺(NHS)和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC·HCl)的混合溶液(溶剂为浓度30mmol/L的2-(N-吗啉代)乙烷磺酸(MES)的缓冲溶液，pH值为5.0左右)20mL加入上述反应液中，于室温下持续搅拌反应24小时，其中壳聚糖、赖氨酸、NHS、EDC的摩尔比为5∶1∶2∶2；反应液过滤后装入透析袋，将透析袋两端扎紧放入去离子水中透析处理，每隔四小时换水一次，换水八次后将透析液放入微波真空干燥机处理，即可得所述新型水溶性抗菌材料。
图1所示为原料壳聚糖和本发明实施例1制备的新型水溶性天然多糖抗菌材料的红外谱图。通过对比两条谱线可以看出(黑色谱线为原料壳聚糖的， 红色谱线为新型水溶性天然多糖抗菌材料的)，原料壳聚糖在3438cm -1处出现的宽峰对应着-NH 2和-OH的伸缩振动，而改性后该处峰位置发生红移且变宽。这个位置的峰变宽还说明，这些-NH 2和-OH存在着强弱不同的分子内和分子间氢键，峰宽的差异，又反映了氢键的强弱。而改性壳聚糖谱图上峰位发生红移且变宽，意味着氢键消失，说明壳聚糖发生了衍生化反应；同时原本在原料壳聚糖1597cm -1处出现的-NH2-弯曲振动消失了，而改性壳聚糖谱图上在1659cm -1和1553cm -1处出现在的峰分别归属于C＝N的伸缩振动峰和N-H的弯曲振动峰。二者谱图上的这些变化充分说明改性功能基团通过氨基成功的接枝到了壳聚糖的分子链上。
图2为本发明实施例1制备的新型水溶性天然多糖抗菌材料按照GB15979-2002《一次性卫生用品卫生标准》中浇板法对金色葡萄球菌进行抗菌性能测试的结果照片，从左到右依次是采用浓度为0.5mg/ml、0.25mg/ml、0.125mg/ml本实施例制备的新型水溶性天然多糖抗菌材料(溶解在中性的去离子水中)以及空白对照组(不添加任何抗菌剂)的培养基涂菌后，在37℃的恒温恒湿培养箱中培养36小时后的抗菌测试结果。该结果表明：本实施例制备的新型水溶性天然多糖抗菌材料对金色葡萄球菌具有良好抑制性能。
对本实施例制备的产品采用浇板法对金色葡萄球菌抑菌率的数据统计结果如下表：
表1 新型水溶性天然多糖抗菌材料对金色葡萄球菌抑菌性能测试结果
Figure PCTCN2018088173-appb-000009
图3为本发明实施例1制备的新型水溶性天然多糖抗菌材料和市售季铵盐壳聚糖衍生物抗菌材料对ME3T3-E1细胞的毒性对比测试结果。该数据测试结果说明：新型水溶性天然多糖抗菌材料细胞毒性较小，细胞毒性明显优于市售季铵盐壳聚糖衍生物抗菌材料。
以上各数据结果说明：新型水溶性天然多糖抗菌材料不但具有良好的抗菌性能，而且在有效抑菌浓度下细胞正常生长，具有良好的生物安全性。
实施例2：
将1.0克壳聚糖加入到100毫升浓度为0.1mol/L的稀盐酸中，60℃的油浴条件下机械搅拌一小时，以便壳聚糖溶解完全，从而得到壳聚糖浓度为0.01g/mL的均匀溶液；将油浴升温至105℃，向壳聚糖溶液体系中一次加入1.05克单氰胺，单氰胺与壳聚糖的摩尔比4∶1，恒温保持搅拌6小时；然后油浴内的反应液降温至室温，将在冰水混合浴中活化3小时的亮氨酸、N-羟基琥珀酰亚胺(NHS)和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC·HCl)的混合溶液(溶剂为30mmol/L的2-(N-吗啉代)乙烷磺酸(MES)的缓冲溶液)20ml加入上述反应液中，于室温下持续搅拌反应10小时，其中壳聚糖、亮氨酸、NHS、EDC的摩尔比为50∶1∶5∶5；反应液过滤后装入透析袋，将透析袋两端扎紧放入去离子水中透析处理，每隔四小时换水一次，换水八次后将透析液放入微波真空干燥机处理，即可得所述新型水溶性天然多糖抗菌材料。
实施例3：
将2.0克壳聚糖加入到100毫升浓度为0.15mol/L的稀盐酸中，60℃的油浴条件下机械搅拌一小时，以便壳聚糖溶解完全，从而得到壳聚糖浓度为0.02g/mL的均匀溶液；将油浴升温至100℃，向壳聚糖油浴液体系中一次加入2.08克双氰胺，双氰胺与壳聚糖的摩尔比2∶1，100℃油浴条件下恒温搅拌12小时；然后油浴内的反应液降温至室温，将在冰水混合浴中活化3小时的异亮氨酸、N-羟基琥珀酰亚胺(NHS)和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC·HCl)的混合溶液(溶剂为浓度30mmol/L的2-(N-吗啉代)乙烷磺酸(MES)的缓冲溶液，pH值为5.0左右)20ml加入上述反应液中，于室温下持续搅拌反应24小时，其中壳聚糖、异亮氨酸、NHS、EDC的摩尔比为20∶1∶4∶4；反应液过滤后装入透析袋，将透析袋两端扎紧放入去离子水中透析处理，每隔四小时换水一次，换水八次后将透析液放入微波真空干燥机处理，即可得所述新型水溶性天然多糖抗菌材料。
实施例4：
将5.0克壳聚糖加入到100毫升浓度为0.15mol/L的稀盐酸中，60℃的油浴条件下机械搅拌一小时，以便壳聚糖溶解完全，从而得到壳聚糖浓度为0.05g/mL的均匀溶液；油浴升温至80℃，向壳聚糖水溶液体系一次加入单氰胺3.91克，单氰胺与壳聚糖的摩尔比3∶1，80℃条件下反应保持24小时；然后油浴内的反应液降温至室温，将在室温下活化2小时的赖氨酸、N-羟基琥珀酰亚胺(NHS)和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC·HCl)的混合溶液(溶剂为浓度30mmol/L的2-(N-吗啉代)乙烷磺酸(MES)的缓冲溶液，PH值为5.0左右)20ml加入上述反应液中，于室温下持续搅拌反应24 小时，其中壳聚糖、赖氨酸、NHS、EDC的摩尔比为5∶1∶2∶2；反应液过滤后装入透析袋，将透析袋两端扎紧放入去离子水中透析处理，每隔五小时换水一次，换水八次后将透析液放入微波真空干燥机处理，即可得所述新型水溶性天然多糖抗菌材料。
实施例5：
将7.0克壳聚糖加入100毫升浓度为0.3mol/L的稀盐酸中，70℃的油浴条件下机械搅拌二小时，以便壳聚糖溶解完全，从而得到壳聚糖浓度为0.07g/mL的均匀溶液；70℃的油浴条件下，向壳聚糖水溶液体系中一次加入单氰胺1.83克，单氰胺与壳聚糖的摩尔比1∶1，恒温保持36小时；然后油浴内的反应液降温至室温，将在室温下2小时的亮氨酸、N-羟基琥珀酰亚胺(NHS)和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC·HCl)的混合溶液(溶剂为浓度30mmol/L的2-(N-吗啉代)乙烷磺酸(MES)的缓冲溶液，PH值为5.0左右)20ml加入上述反应液中，于室温下持续搅拌反应24小时，其中壳聚糖、亮氨酸、NHS、EDC的摩尔比为5∶1∶4∶4；反应液过滤后装入透析袋，将透析袋两端扎紧放入去离子水中透析处理，每隔四小时换水一次，换水八次后将透析液放入微波真空干燥机处理，即可得所述新型水溶性天然多糖抗菌材料。
实施例6：
将10克壳聚糖加入到100毫升浓度为0.5mol/L的稀盐酸中，60℃的油浴条件下机械搅拌两小时，以便壳聚糖溶解完全，从而得到壳聚糖浓度为0.1g/mL的均匀溶液；60℃的油浴条件下，向壳聚糖水溶液体系中一次加入双氰胺2.61克，双氰胺与壳聚糖的摩尔比0.5∶1，60℃条件下反应保持48小时；然后油浴内的反应液降温至室温，将在室温下2小时的异亮氨酸、N-羟基琥珀酰亚胺(NHS)和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC·HCl)的混合溶液(溶剂为浓度30mmol/L的2-(N-吗啉代)乙烷磺酸(MES)的缓冲溶液，PH值为5.0左右)30ml加入上述反应液中，于35℃水浴中持续搅拌反应24小时，其中壳聚糖、异亮氨酸、NHS、EDC的摩尔比为4∶1∶3∶3；反应液过滤后装入透析袋，将透析袋两端扎紧放入去离子水中透析处理，每隔四小时换水一次，换水八次后将透析液放入微波真空干燥机处理，即可得所述新型水溶性天然多糖抗菌材料。
显然，本发明的上述实施例仅仅是为清楚地说明本发明所作的举例，而并非是对本发明的实施方式的限定，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，这里无法对所有 的实施方式予以穷举，凡是属于本发明的技术方案所引伸出的显而易见的变化或变动仍处于本发明的保护范围之列。

Claims (10)

  1. 一种新型水溶性天然多糖抗菌材料，其特征在于，所述天然多糖抗菌材料的分子结构式如式1所示：
    Figure PCTCN2018088173-appb-100001
    R 1为：
    Figure PCTCN2018088173-appb-100002
    R 2为：
    Figure PCTCN2018088173-appb-100003
    其中，x、y、n为自然数，0＜x≦10 7，0＜y≦10 7，10 2≦n≦10 7。
  2. 一种制备如权利要求1所述新型水溶性天然多糖抗菌材料的方法，其特征在于，包括如下步骤：
    1)将壳聚糖溶解到稀酸溶液中，得到壳聚糖的稀酸水溶液；
    2)向步骤1)所得壳聚糖的稀酸水溶液中加入单氰胺或双氰胺，进行反应；
    3)将氨基酸活化溶液加入步骤2)的反应体系中，进行酰胺化反应；
    4)加入盐酸羟胺终止反应；
    5)反应液过滤后用去离子水透析，进行微波真空干燥处理，即得新型水溶性天然多糖抗菌材料。
  3. 根据权利要求2所述的方法，其特征在于，步骤1)中所述壳聚糖数均分子量为10 2-10 7，脱乙酰度为50-100％；
    所述的稀酸为盐酸或醋酸，酸的浓度为0-0.5mol/L；
    所述壳聚糖的稀酸水溶液的浓度为0.001-0.1g/mL。
  4. 根据权利要求2所述的方法，其特征在于，步骤1)中所述溶解条件为：60-110℃之间恒温搅拌。
  5. 根据权利要求2所述的方法，其特征在于，步骤2)中所述单氰胺或双氰胺与壳聚糖的摩尔比为0.5-5:1；
    反应条件为：60-110℃之间恒温搅拌6-48小时。
  6. 根据权利要求2所述的方法，其特征在于，步骤3)中，所述氨基酸活化溶液通过以下方法得到：
    氨基酸、N-羟基琥珀酰亚胺和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐溶解于2-(N-吗啉代)乙烷磺酸缓冲液中，在0-35℃之间恒温搅拌活化0.5-3小时；
    所述2-(N-吗啉代)乙烷磺酸缓冲液的浓度为30mmol/L，pH值为5.0±0.5。
  7. 根据权利要求6所述的方法，其特征在于，所述1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐与氨基酸的摩尔比为0.5-5:1，N-羟基琥珀酰亚胺与1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐的摩尔比为1:1。
  8. 根据权利要求2-7任一所述的方法，其特征在于，所述氨基酸为亮氨酸、异亮氨酸或赖氨酸。
  9. 根据权利要求2所述的方法，其特征在于，所述壳聚糖与氨基酸的摩尔比为1-50:1；
    步骤3)中酰胺化反应温度为0-35℃。
  10. 根据权利要求2所述的方法，其特征在于，步骤5)中，去离子水透析过程中，每5-10小时换水一次，换水6-8次。
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