WO2018014373A1 - 羧甲基可得然胶水溶液或水凝胶 - Google Patents

羧甲基可得然胶水溶液或水凝胶 Download PDF

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WO2018014373A1
WO2018014373A1 PCT/CN2016/093011 CN2016093011W WO2018014373A1 WO 2018014373 A1 WO2018014373 A1 WO 2018014373A1 CN 2016093011 W CN2016093011 W CN 2016093011W WO 2018014373 A1 WO2018014373 A1 WO 2018014373A1
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hydrogel
carboxymethyl
aqueous solution
gel
derived
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赵小敏
蔡志祥
张洪斌
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上海交通大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/07—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media from polymer solutions
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075—Macromolecular gels
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/02—Dextran; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/10—General cosmetic use
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/02—Dextran; Derivatives thereof

Definitions

  • the invention belongs to the field of polymer materials, in particular to a low-concentration low-substituted carboxymethyl-derived gelatin aqueous solution or physical hydrogel, and a preparation method and application thereof.
  • Curdlan also known as keide
  • Curdlan is a D-glucan which is produced by fermentation of Alcaliges faecalis and is all linked by ⁇ -1,3 glycosidic bonds.
  • Naturally available gelatin has a molecular weight of tens of thousands to millions, and the solid is a white powder. It is non-toxic and tasteless, insoluble in water, but soluble in alkali solution and DMSO solvent.
  • FDA United States Food and Drug Administration
  • Natural macromolecular polysaccharides have excellent properties such as hydrophilicity, biocompatibility and biodegradability, and are ideal polymers capable of forming hydrophilic colloids.
  • the gel property of the gel can be obtained.
  • the aqueous suspension can form a low-intensity thermoreversible gel and a high-intensity thermal irreversible gel according to the heating temperature (Zhang, HB et al., International Journal Biological Macromolecules). , 2002, 30: 7-16).
  • the gum is insoluble in water, cannot form an aqueous solution, and can only form an unstable aqueous suspension.
  • This aqueous suspension does not have the thickening effect normally possessed by the polysaccharide solution, and the obtainable gel hydrogel formed by heating the aqueous suspension is also opaque.
  • These problems have greatly limited the widespread use of available adhesives. Since a large amount of hydroxyl groups are present in the molecule of the gel, chemical groups can introduce different groups on the repeating unit, on the one hand, the solubility can be improved, and the introduction of different substituents can also give a stronger gel. Biological activity.
  • Carboxylated methylated gels have received much attention due to their good antitumor activity and strong immunopotentiating activity (Sasaki T. et al., Cancer Research, 1978, 38(2): 379-383; Sasaki T. et al., European Journal of Cancer, 1979, 15(2): 211-215; Saito, H. et al., Carbohydrate Research, 1991, 217: 181-190), can be used as an immunization in immunotherapeutics Additives and drug sustained release carriers (Na K.
  • Polysaccharide hydrogels are generally classified into chemical gels and physical gels according to the way of cross-linking.
  • U.S. Patent No. 2,013,196, 944, issued to U.S. Pat. US005574023A describes an intramolecular crosslinking method for 1,3- ⁇ -D-glucan, in which chemistry including diamine, dihydrazide, etc. is also used.
  • Crosslinker These chemical gels are formed by covalent bond crosslinking, and the chemical cross-linking agent or organic solvent used in the preparation process is difficult to completely remove, and if it remains in the gel, it may cause potential cytotoxicity.
  • the physical hydrogel is formed by means of ion crosslinking such as electrostatic interaction, hydrogen bonding, crystallization or hydrophobic interaction, so that the disadvantages of the above chemical gel can be overcome, and toxic chemical crosslinking agents and Use of organic solvents.
  • ion crosslinking such as electrostatic interaction, hydrogen bonding, crystallization or hydrophobic interaction
  • Patent CN200910054602.4 describes a method for preparing a carboxymethyl-derived gel physical hydrogel by freezing and thawing to form a high degree of substitution (degree of substitution 0.50-1.0), which expands its application range to some extent.
  • degree of substitution 0.50-1.0
  • the gel can improve the water solubility and retain its gel properties.
  • the physical gel can be prepared by controlling the concentration and temperature.
  • the preparation method of the invention is simple, the hydrogel can be formed under normal temperature conditions, and no other chemical reagents need to be added, so the obtained hydrogel has wider application in thickener, immuno-cosmetic and drug sustained-release carrier. prospect.
  • the preparation method of the low-concentration low-substituted carboxymethyl-derived gel physical hydrogel of the present invention prepares an aqueous solution of carboxymethyl-derived gelatin by adjusting the degree of substitution and concentration, and forms a gel by standing naturally.
  • the viscosity of the solution and the strength of the gel can be adjusted by adjusting the concentration and degree of substitution of the carboxymethyl-derived gel.
  • the present invention prepares a carboxymethyl-derived gel physical hydrogel by controlling the degree of substitution and concentration, and the method is simpler and more convenient, and does not introduce any toxic or side effects to the organism during gel formation.
  • the low-concentration low-substituted carboxymethyl-derived gel used in the present invention has a degree of substitution (DS) ranging from 0.01 to 0.5, and its molecular formula is:
  • R is CH 2 COONa or H
  • the degree of substitution of CH 2 COONa is 0.01 to 0.5
  • the degree of polymerization n is in the range of 300 to 6000.
  • the preparation method of the low-concentration low-substituted carboxymethyl-derived gel physical hydrogel of the invention comprises the following steps Step:
  • the aqueous solution of the low-substituted carboxymethyl-derived gelatin obtained in the step (1) is controlled at room temperature, and a low-concentration low-substituted carboxymethyl group can be obtained by natural standing to form a physical hydrogel.
  • the water is preferably ultrapure water or deionized water
  • the room temperature refers to a general room temperature, for example 5 to 40 ° C, preferably 20 to 25 ° C, without precise control.
  • the hydrogel obtained by the invention has a low content of carboxymethyl keide gum, the mass percentage is only 0.01% to 2%, and the balance is water.
  • the thickener is characterized by excellent thickening and gelling effects at low concentrations, and is particularly useful in aqueous dispersions, providing desirable rheological properties, clarity, and aesthetic properties. Therefore, as a thickener, it has a high water solubility, a high thickening action, and a high shear thinning property, and has the ability to gel at a low concentration, and the formed aqueous solution and hydrogel have high transparency.
  • the new thickener has wide application value in many fields such as food, cosmetics, biomedical materials, detergents, detergents, oil extraction, paints and the like.
  • carboxymethyl-derived gel has certain immunological activity and anti-tumor activity
  • the thickener has potential application value especially in immuno-cosmetic, drug-releasing carrier, etc., and its excellent biological activity has more hydrophilic activity than other hydrophilic colloids. A bigger advantage.
  • Figure 1 is a graph showing the dependence of the elastic modulus G' and the viscous modulus G" of a different concentration of carboxymethyl-derived gel at 25 °C on the frequency ⁇ under the same degree of substitution in a preferred embodiment of the present invention.
  • Figure 2 is a graph showing the dependence of the complex viscosity ⁇ * and frequency ⁇ at 25 ° C for different concentrations of carboxymethyl-derived gel hydrogels under the same degree of substitution in a preferred embodiment of the present invention
  • Figure 3 is a graph showing the dependence of the complex viscosity ⁇ * on the frequency ⁇ at 25 ° C for aqueous solutions or hydrogels of different degrees of substitution with different degrees of substitution in a comparative example of the present invention.
  • the preparation method of the carboxymethyl-derived gel physical hydrogel of Example 2 was substantially the same as that of Example 1, except that the mass concentration of the aqueous solution of the carboxymethyl-derived gelatin compound disposed in the step (1) was 0.5%.
  • the preparation method of the carboxymethyl-derived gel physical hydrogel of Example 3 was substantially the same as that of Example 1, except that the mass concentration of the aqueous solution of the carboxymethyl-derived gelatin compound disposed in the step (1) was 0.4%.
  • the system of Example 3 has a low frequency G' ⁇ G" and a high frequency G'>G" and both show a frequency dependence; as can be seen from Fig. 2, the complex viscosity linearly decreases with frequency. It exhibits high thickening and shear thinning properties.
  • the preparation method of the carboxymethyl-derived gel physical hydrogel of Example 4 was substantially the same as that of Example 1, except that the mass concentration of the aqueous solution of the carboxymethyl-derived gelatin compound disposed in the step (1) was 0.3%.
  • the system G' of the embodiment 4 is smaller than G" and has a higher frequency dependence over the entire test frequency range; as can be seen from Fig. 2, the complex viscosity linearly decreases with frequency. High thickening and shear thinning characteristics.
  • the strength of the gel obtained in Example 5 was greater than that of the gel obtained in Example 1.
  • the strength of the gel obtained in Example 6 was less than that of the gel obtained in Example 1.
  • the temperature of the uncarboxymethylated modified gelatin suspension prepared in the step (1) is controlled at room temperature, and after standing naturally, neither an aqueous solution nor a hydrogel can be formed.
  • the temperature of the aqueous solution of the high-substituted carboxymethyl group which is prepared in the step (1) is controlled at room temperature, and is still an aqueous solution after standing still, and a hydrogel cannot be formed.
  • carboxymethyl can be 0.05g, 0.10g dissolved in ultrapure water, respectively prepared to a mass concentration of 0.5%, 1% An aqueous solution of carboxymethyl can be obtained;
  • the temperature of the aqueous solution of the carboxymethyl-derived gelatin prepared in the step (1) is controlled at room temperature, and the aqueous solution of the carboxymethyl-formable gel or hydrogel is formed by standing naturally.
  • the ⁇ * value of the low-substituted carboxymethyl-derived gel is about 70 times that of the high-substituted carboxymethyl-derived ⁇ * value;
  • the ⁇ * value of the low-substituted carboxymethyl-derived gel is about 500 times that of the high-substituted carboxymethyl-derived ⁇ * value, and it can be seen that the low-substituted carboxymethyl group can be obtained. Shows an extremely significant thickening effect.

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Abstract

一种低浓度低取代度羧甲基可得然胶水溶液或水凝胶及其制备方法和应用。制备方法简单，常温条件下即可形成高粘度的水溶液或水凝胶，且水凝胶的制备无需加入任何其它有机溶剂或化学交联剂，无需调节pH值、也无需引入其它金属离子。其作为增稠剂应用时具有优异的低浓度下的增稠和胶凝效果，特别适用于水性分散体系，能提供期望的流变特性、清澈性以及美观性。该增稠剂具有高水溶性、高增稠作用和高剪切变稀特性，具有低浓度下凝胶化的能力，所形成的溶液和水凝胶具有高透明性，因此所得到的水凝胶在增稠剂、免疫化妆品及药物缓释载体等方面具有广阔的应用前景。

Description

[根据细则37.2由ISA制定的发明名称]　羧甲基可得然胶水溶液或水凝胶 技术领域
本发明属于高分子材料领域，特别涉及一种低浓度低取代度羧甲基可得然胶水溶液或物理水凝胶及其制备方法和应用。
背景技术
可得然胶(Curdlan，又名可德胶)是由粪产碱杆菌(Alcaliges faecalis)发酵产生的一种全部由β-1,3糖苷键连接而成的D-葡聚糖。天然可得然胶分子量在数万至上百万之间，固体为白色粉末，无毒无味，不溶于水，但可溶于碱溶液和DMSO溶剂。可得然胶于1996年获美国食品和药物管理局(FDA)认证，可在食品中用作添加剂。我国于2006年5月批准可得然胶用作食品添加剂(张洪斌，多糖及其改性材料，pp90-116，化学工业出版社，2014)。天然大分子多糖具有亲水性、生物相容性和可生物降解性等优良特性，是比较理想的能形成亲水胶体的高分子。可得然胶具有的凝胶特性，其水悬浮液根据加热温度的高低，既能形成低强度热可逆凝胶，亦能形成高强度热不可逆凝胶(Zhang,H.B.等人,International Journal Biological Macromolecules,2002,30:7-16)。
然而可得然胶不溶于水，不能形成水溶液，只能形成不稳定的水悬浮液。这种水悬浮液不具有多糖溶液通常具有的增稠效果，并且通过加热水悬浮液形成的可得然胶水凝胶也不透明。这些问题大大限制了可得然胶的广泛应用。由于可得然胶分子中存在大量羟基，通过化学改性可在重复单元上引入不同的基团，一方面可以改善其溶解性，同时不同取代基的引入还可赋予可得然胶更强的生物活性。如羧甲基化的可得然胶由于具有良好的抗肿瘤活性和较强的免疫提高活性较早就得到关注(Sasaki T.等人,Cancer Research,1978,38(2):379-383；Sasaki T.等人,European Journal of Cancer,1979,15(2):211-215；Saito,H.等人,Carbohydrate Research,1991,217:181-190)，可被用作免疫化妆品中的免疫添加剂以及药物缓释载体(Na K.等人,Journal of Controlled Release,2000,69(2):225-236；Rafigh S.M.等人,International Journal of Biological Macromolecules,2016,87:603-610；Li L.等人,Nanotechnology,2010,21(26):265601)。
多糖水凝胶按交联方式的不同一般分为化学凝胶和物理凝胶两类。美国专利US20130196944A1描述了化学交联β-D-葡聚糖作为新型组织填充材料的应用，其中使用了1,4-丁二醇二缩水甘油醚、二甲基亚砜等交联剂；美国专利US005574023A描述了1,3-β-D-葡聚糖的分子内交联方法，其中也使用了包括二胺、二酰肼等化学 交联剂。这些化学凝胶是通过共价键交联的方法形成的，制备过程中使用的化学交联剂或有机溶剂难以完全去除，如果在凝胶中有残留则会造成潜在的细胞毒性。迄今的一些研究表明，化学交联产物的安全性、副作用和应用风险尚有很大的不确定性(Reichenbach S.等人,Arthritis Care & Research,2007,57(8):1410-1418)。
物理水凝胶是通过诸如静电作用的离子交联、氢键作用、结晶或疏水作用所导致的分子交联等方式形成，因此可以克服上述化学凝胶的弊端，避免了毒性化学交联剂和有机溶剂的使用。可得然胶经羧甲基改性后，尽管水溶性明显提高，但如果取代度过高则会丧失原有的在加热条件下形成凝胶的特性(Jin Y.等人,Carbohydrate Research,2006,341(1):90-99)。专利CN200910054602.4介绍了一种通过冷冻解冻来形成高取代度(取代度为0.50～1.0)的羧甲基可得然胶物理水凝胶的制备方法，一定程度上拓展了其应用范围。但较高的取代度使得可得然胶通常只能通过冷冻解冻法形成水凝胶。
经对现有技术文献及专利的检索发现，目前尚未有对低取代度羧甲基可得然胶的增稠作用和凝胶性质进行探究的公开报道。
发明内容
有鉴于现有技术的上述缺陷，本发明的目的在于提供一种低浓度低取代度羧甲基可得然胶水溶液或物理水凝胶及其制备方法和应用。可得然胶经过较低程度的羧甲基化后，既可提高水溶性，又能保留其凝胶特性，仅通过控制浓度和温度的方法即可制备得到可得然胶物理水凝胶。本发明的制备方法简单，常温条件下即可形成水凝胶，且无需加入任何其它化学试剂，因此所得到的水凝胶在增稠剂、免疫化妆品及药物缓释载体方面更具有广阔的应用前景。
本发明的低浓度低取代度羧甲基可得然胶物理水凝胶的制备方法通过调节取代度和浓度配制羧甲基可得然胶水溶液，并通过自然静置形成凝胶。溶液的粘度和凝胶的强度可以通过调节羧甲基可得然胶的浓度和取代度进行调节。与现有技术相比，本发明通过控制取代度和浓度制备羧甲基可得然胶物理水凝胶，方法更为简单方便，且形成凝胶过程中，不引入任何对生物体有毒副作用的有机溶剂或化学交联剂，无需调节pH值、也无需引入其他金属离子。
本发明采用的低浓度低取代度羧甲基可得然胶的取代度(DS)范围为0.01～0.5，其分子式为：
Figure PCTCN2016093011-appb-000001
其中，R为CH2COONa或H，CH2COONa的取代度为0.01～0.5，聚合度n的取值范围为300～6000。
本发明的低浓度低取代度羧甲基可得然胶物理水凝胶的制备方法，包括以下步 骤：
(1)将低取代度羧甲基可得然胶溶于水中，在室温～90℃下搅拌使其完全溶解，配成羧甲基可得然胶水溶液，其中所述羧甲基可得然胶的质量百分比浓度为0.01％～2％；
(2)将步骤(1)中获得的低取代度羧甲基可得然胶水溶液控制在室温，通过自然静置形成低浓度低取代度羧甲基可得然胶物理水凝胶。
所述水优选为超纯水或去离子水，所述室温指一般性的室内温度，例如5～40℃，优选为20～25℃，无需精确控制。
本发明得到的水凝胶中羧甲基可德胶的含量低，质量百分比仅为0.01％～2％，余量为水。该增稠剂的特点在于优异的低浓度条件下的增稠和胶凝效果，特别适用于水性分散体系，能提供期望的流变特性、清澈性以及美观性质。因此，作为增稠剂使用具有高水溶性、高增稠作用和高剪切变稀特性，具有低浓度下凝胶化的能力，所形成的水溶液和水凝胶具有高透明性。该新型增稠剂在食品、化妆品、生物医药材料、洗涤剂、清洁剂、采油、涂料等诸多领域有广泛的应用价值。由于羧甲基可得然胶还具有一定的免疫活性和抗肿瘤活性，该增稠剂特别在免疫化妆品、药物缓释载体等方面有着潜在应用价值，其优良的生物活性较其它亲水胶体具有更大的优势。
附图说明
图1是本发明一个较佳实施例中，相同取代度条件下不同浓度羧甲基可得然胶水凝胶在25℃下的弹性模量G’和粘性模量G”与频率ω的依赖关系图；
图2是本发明一个较佳实施例中，相同取代度条件下不同浓度羧甲基可得然胶水凝胶在25℃下的复数粘度η*与频率ω的依赖关系图；
图3是本发明一个对比例中，不同浓度不同取代度羧甲基可得然胶水溶液或水凝胶在25℃下的复数粘度η*与频率ω的依赖关系图。
具体实施方式
下面给出本发明的具体实施例作详细说明。本实施例在以本发明技术方案为前提下进行实施，给出了详细的实施方式和具体的操作过程，但本发明的保护范围不限于下述的实施例。
实施例1：
实施例1的羧甲基可得然胶物理水凝胶的制备方法如下：
(1)准确称取DS＝0.1、n＝3000的羧甲基可得然胶0.10g溶于超纯水中，配制质量浓度为1％的羧甲基可得然胶水溶液；
(2)将步骤(1)中配制的羧甲基可得然胶水溶液温度控制在室温，通过自然 静置形成羧甲基可得然胶水凝胶。
利用TA AR G2型旋转流变仪测试实施例1得到的羧甲基可得然胶水凝胶的弹性模量G’、粘性模量G”和复数粘度η*随频率ω的变化，结果分别示于图1和图2。从图1可以看到，实施例1的体系G’>G”且几乎不随频率变化；从图2可以看到，其复数粘度随频率线性快速下降，表现出高增稠作用和高剪切变稀特性。
实施例2：
实施例2的羧甲基可得然胶物理水凝胶的制备方法与实施例1基本相同，区别仅在于步骤(1)中配置的羧甲基可得然胶水溶液的质量浓度为0.5％。
从图1可以看到，实施例2的体系G’>G”且随频率增加略有增大；从图2可以看到，其复数粘度随频率线性下降，表现出高增稠作用和高剪切变稀特性。
实施例3：
实施例3的羧甲基可得然胶物理水凝胶的制备方法与实施例1基本相同，区别仅在于步骤(1)中配置的羧甲基可得然胶水溶液的质量浓度为0.4％。
从图1可以看到，实施例3的体系低频时G’<G”而高频时G’>G”且均显示频率依赖性；从图2可以看到，其复数粘度随频率线性下降，表现出高增稠作用和剪切变稀特性。
实施例4：
实施例4的羧甲基可得然胶物理水凝胶的制备方法与实施例1基本相同，区别仅在于步骤(1)中配置的羧甲基可得然胶水溶液的质量浓度为0.3％。
从图1可以看到，在整个测试频率范围内，实施例4的体系G’均小于G”并有较高的频率依赖性；从图2可以看到，其复数粘度随频率线性下降，表现出高增稠作用和剪切变稀特性。
实施例5：
实施例5的羧甲基可得然胶物理水凝胶的制备方法与实施例1基本相同，区别仅在于步骤(1)中采用的羧甲基可得然胶的取代度DS＝0.02。实施例5所得凝胶的强度大于实施例1所得凝胶的强度。
实施例6：
实施例6的羧甲基可得然胶物理水凝胶的制备方法与实施例1基本相同，区别仅在于步骤(1)中采用的羧甲基可得然胶的取代度DS＝0.45。实施例6所得凝胶的强度小于实施例1所得凝胶的强度。
对比例1：
(1)分别准确称取DS＝0、n＝3000的未羧甲基化改性的可得然胶0.001g、0.01g、0.10g和0.20g溶于超纯水中，配制质量浓度分别为0.01％、0.1％、1％和2％的未羧甲基化改性的可得然胶水悬浊液；
(2)将步骤(1)中配制的未羧甲基化改性的可得然胶水悬浮液温度控制在室温，自然静置后既不能形成水溶液，也不能形成水凝胶。
对比例2：
(1)准确称取n＝3000而取代度分别为DS＝0.6、0.7、0.8、0.9的羧甲基可得然胶各0.20g分别溶于超纯水中，分别配制成质量浓度为2％的羧甲基可得然胶水溶液；
(2)将步骤(1)中配制的高取代羧甲基可得然胶水溶液温度控制在室温，自然静置后仍为水溶液，不能形成水凝胶。
对比例3：
(1)准确称取n＝3000而取代度分别为DS＝0.1、0.8的羧甲基可得然胶0.05g、0.10g溶于超纯水中，分别配制成质量浓度为0.5％、1％的羧甲基可得然胶水溶液；
(2)将步骤(1)中配制的羧甲基可得然胶水溶液温度控制在室温，通过自然静置形成羧甲基可得然胶水溶液或水凝胶。
利用TA AR G2型旋转流变仪测试对比例3得到的羧甲基可得然胶水溶液或水凝胶的复数粘度η*随频率ω的变化，结果示于图3。从图3可以看到，在相同浓度下，低取代度羧甲基可得然胶(DS＝0.1)的复数粘度η*均远大于高取代度羧甲基可得然胶(DS＝0.8)的复数粘度η*。以频率ω＝1rad/s为例，浓度为0.5％时，低取代度羧甲基可得然胶的η*值约为高取代度羧甲基可得然胶η*值的70倍；而浓度为1％时，低取代度羧甲基可得然胶的η*值约为高取代度羧甲基可得然胶η*值的500倍，可见低取代度羧甲基可得然胶表现出了极其显著的增稠作用。
以上详细描述了本发明的较佳具体实施例。应当理解，本领域的普通技术无需创造性劳动就可以根据本发明的构思做出诸多修改和变化。因此，凡本技术领域中技术人员依本发明的构思在现有技术的基础上通过逻辑分析、推理或者有限的试验可以得到的技术方案，皆应在由权利要求书所确定的保护范围内。

Claims (10)

  1. 一种羧甲基可得然胶水溶液或水凝胶，其特征在于，所述羧甲基可得然胶的分子式为：
    Figure PCTCN2016093011-appb-100001
    其中，R为CH2COONa或H，CH2COONa的取代度为0.01～0.5，n为300～6000，所述水溶液可形成所述水凝胶。
  2. 如权利要求1所述的羧甲基可得然胶水溶液或水凝胶，其特征在于，所述水溶液中所述羧甲基可得然胶的质量百分比浓度为0.01％～2％。
  3. 如权利要求2所述的羧甲基可得然胶水溶液或水凝胶，其特征在于，所述水溶液的制备方法包括以下步骤：
    (1)将所述羧甲基可得然胶溶于水中，在室温～90℃下搅拌使其完全溶解，形成所述水溶液。
  4. 如权利要求2所述的羧甲基可得然胶水溶液或水凝胶，其特征在于，所述水凝胶的制备方法包括以下步骤：
    (1)将所述羧甲基可得然胶溶于水中，在室温～90℃下搅拌使其完全溶解，形成所述水溶液；
    (2)将步骤(1)中获得的所述水溶液控制在室温，通过自然静置形成所述水凝胶。
  5. 如权利要求3或4所述的羧甲基可得然胶水溶液或水凝胶，其特征在于，所述水为超纯水或去离子水。
  6. 如权利要求3或4所述的羧甲基可得然胶水溶液或水凝胶，其特征在于，所述室温为5～40℃。
  7. 如权利要求1-4中任一项所述的羧甲基可得然胶水溶液或水凝胶作为增稠剂的应用。
  8. 如权利要求7所述的羧甲基可得然胶水溶液或水凝胶作为增稠剂的应用，其特征在于，所述增稠剂添加在食品、化妆品、生物医药材料、洗涤剂、清洁剂、采油、涂料中。
  9. 如权利要求8所述的羧甲基可得然胶水溶液或水凝胶作为增稠剂的应用，其特征在于，所述化妆品为免疫化妆品。
  10. 如权利要求8所述的羧甲基可得然胶水溶液或水凝胶作为增稠剂的应用，其特征在于，所述生物医药材料为药物缓释载体。
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