1. Introduction
Osteoarthritis, characterized by progressively degen-eration or loss of articular cartilage, is the most common form of arthritis. Tissue engineering has shown great promise as a strategy to develop bio-logical substitutes to restore, replace or regenerate the defective tissue [1]. Scaffolds made of poly-meric biomaterials offer support for cell attach-ment, proliferation and differentiation [2, 3]. Encap-sulation of living cells within a semi-permeable membrane is a simple one-step procedure with char-acteristics of homogenous cell distribution and excel-lent cell viability [4, 5]. Its unique self-assembled capability makes it suitable for injectable scaffolds for in situ tissue regeneration. Recent advances in microfluid designs have brought the field of micro -fluidics to the forefront of the preparation of micro-or nano-gels for cell encapsulation [6–8].
Many naturally derived biomaterials have been used for encapsulation, such as sodium alginate [9] and agarose [10]. However, these biomaterials have limited ability to support cell attachment, growth and differentiation, resulting in low cell viability and growth [11]. Carboxymethyl cellulose (CMC) is a water-soluble, biodegradable and biocompatible derivative of cellulose. Its hydrophilic carboxylic or hydroxyl groups serve as active sites for preparing CMC gels. Physical-crosslinking CMC gels via
supermolecular [12] and ionic [13] interaction are simple to be produced, but usually questioned by their reversibility.
Chemical-crosslinking provides CMC gels a more stable three-dimensional network. For example, divinyl sulfone [14], epichlorohydrin [15], aldehy-des [16, 17], fumaric acid [18] and citric acid [19] have been used as crosslinkers to form CMC and CMC composite gels. Monomers with double bond, such as N-isopropyl acrylamide [20] and partially neutralized acrylic acid/rectorite [21], have been ini-tiated by ammonium persulfate and coupled onto CMC backbones via methylene bisacrylamide (crosslinker). These chemical crosslinkers are lim-ited for the applications in biomedical or pharmaceu-tical areas because of their toxicity or the stimula-tory reaction to the encapsulated bioactive molecules or live cells. A bio-based carbodiimide crosslinker has been used to prepare chitosan/CMC microgels [22], indicating a very low efficiency of crosslink-ing reaction. Another synthetic route is to form CMC gels via functional groups of both components with-out any crosslinker, for example, hydrazide-func-tionalized CMC/aldehyde-functionalized dextran, suggested by Kesselman et al. [23]. They have intro-duced the two reactive streams into a continuous oil solution simultaneously through two separate inlets of a microfluidics device. However, the premixing of the reactive streams before the formation of droplets often resulted in the blockage of small opening of the microfluidics.
Enzymatic reaction has been extensively studied owing to its low toxicity, mild reaction, stereo-chemistry, and high reaction velocity, high enantio-, regio- and chemo-selectivity [24]. Horseradish per-oxidise/hydrogen peroxide (HRP/H2O2) is a com-mon enzymatic system, where peroxidases (oxi-doreductases) catalyzes the oxidation of donors using H2O2, resulting in polyphenols linked at the aromatic ring by C–C and C–O coupling of phenols [25]. DeV older et al.[26] have prepared hydrogels of alginate grafted with pyrrole groups through a HRP-activated crosslinking reaction for drug release system. We designed a special microfluidic device to prepare monodisperse CMC-based microdroplets [27]. In this work, we synthesized 4-hydroxybenzy-lamine modified CMC (CMC-Ph) with different molecular weight and prepared CMC-Ph microgels through an enzymatic reaction. The properties of CMC-Ph that influenced the formation of microgels were studied. Moreover, cells were encapsulated in CMC-Ph microgels to study the biocompatibility of CMC-Ph and the microfluidic approach through the enzymatic crosslinking reaction.
2. Experimental
2.1. Materials
1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), N-hydroxysulfosuccinimide (NHS), HRP (250units/mg), lecithin, 4-hydroxyben-zylamine, 1-hydroxybenzotriazole hydrate (HOBT) and 2-(4-morpholino)ethanesulfonic acid (MES) were obtained from Qiyun Biotech (China). Aqueous H2O2(30%, w/w) and liquid paraffin were purchased from Dalu Chemical Reagent (China). All reagents were of analytical grade and used as received. CMC with M w of 1.0!105(CMC10), 2.0!105(CMC20) and 3.0!105(CMC30) were purchased from Jingchun Chemical Reagent (China). CMC-Ph was synthe-sized according to our previous study [27]: Briefly, CMC and 4-hydroxybenzylamine were dissolved in MES buffer (50mM, pH6.0) at 1.0 and 0.6%, respectively. NHS, HOBt and EDC were added at a weight ratio of 1:0.26:0.68:0.70 (CMC:NHS:HOBt: EDC). The solution was magnetic stirred for 24hours and dialyzed against deionized water using an ultrafiltration membrane (molecular weight cut-off= 3500Da) at 25°C for 4days. The resultant polymer solution was enriched by a rotary evapora-tor (100rpm) at 50°C and lyophilized.
2.2. Preparation of CMC-Ph microgels
A co-flowing microfluidic device with an inner diameter of 260μm and an outer diameter of 510μm was used for preparing CMC-Ph microparticles. The continuous liquid paraffin phase was prepared as follows: In brief, 250mL of liquid paraffin con-taining 1.25mL H2O2was magnetically stirred for 12hours at 25°C and centrifuged at 2000rpm for 10minutes. Lecithin was dissolved at 3.0% (w/v) into the upper liquid paraffin containing H2O2. CMC-Ph aqueous solution containing HRP as the dispersed phase was injected into the microfluidic device using a micro-syringe pump (Baoding Longer TS-1B/W0109-1B, China), and the continuous phase was injected into an inlet in a perpendicular direction. The particles flew along the channel and finally collected.
2.3. Preparation of cell-laden CMC-Ph
microgels
The lyophilized CMC-Ph was sterilized by expo-sure to epoxyethane vapor. CMC-Ph (~0.2g) was dissolved in 4mL of Dulbecco’s modified Eagle medium (DMEM, Hyclone, USA). HRP was then dissolved at 1mg/mL in DMEM, and the solution was kept at 37°C. The chondrocytic cell line A TDC5 (Sigma, USA) of sixth passage was trypsinized at a density of 1!107cells/mL. 1mL of cell suspension was added into the CMC-Ph solution containing HRP, which injected as the dispersed phase at a rate of 50μL/min. The continuous liquid paraffin phase was injected at a rate of 10mL/min. The resulted microgels were collected and centrifuged at 2000rpm for 5min. Phosphate buffer saline (PBS, pH= 7.4, Gibco, USA) was added to the tube, fol-lowed by centrifuging at 2000rpm for 5min twice. The collected cell-laden CMC-Ph microgels were removed into 6-well cell culture dishes (Corning, USA). Cells enclosed in microgels were incubated in DMEM supplemented with 10% (v/v) fetal bovine serum (FBS, Gibco, USA) in a humidified atmos-phere at 37°C under 5% CO2. The medium was exchanged for fresh medium every 2days, and a new cell culture dish was replaced every 4 days till cell-culturing for 40days. The morphology of the cell-laden CMC-Ph microgels was evaluated under an inverted light microscope (Nikon ECLIPSE TS100, Japan).
2.4. Characterization
A Bruker (Germany) Vertex 70 Fourier transform infrared spectrometry (FTIR) was used to obtain infrared analyses of 4-hydroxybenzylamine, CMC and CMC-Ph using KBr pellet method. The spectra comprised 64scans at a resolution of 1cm–1in 4000~400cm–1spectral range.
1H nuclear magnetic resonance (NMR, Drx-400 Bruker, Germany) spectra were achieved at 400MHz using deuterated water (D2O) as solvent in the pres-ence of tetramethylsilane as an internal standard. Graft density of phenols in CMC-Ph was calculated by measuring the absorbance at 275nm of CMC-Ph solutions using a Thermo (USA) Evolution 300 UV-VIS spectrometer. The absorbance being measured was compared with a 4-hydroxybenzylamine stan-dard curve. The graft density of phenols then calcu-lated from the ratio of phenols to 100repeat units of CMC. The data was the mean of five samples.Molecular weight and polydispersity index (PDI) of CMC and CMC-Ph were determined by a Water (USA) 515–410gel permeation chromatography (GPC). Weight-average (M w) and number-average (M n) molecular weight were expressed with respect to polyethyleneglycol standards. Rheological behavior of CMC-Ph solutions with different concentrations was measured using a TA (USA) ARES/RFS rotational viscometer at 16 and 30°C, respectively. The solutions were prepared by mass using a XS105DU balance (Mettler Toledo, Switzerland) with a precision of 10–5g. The employed shear rate varied from 0.01 to 250s–1, and viscosity and stress were identified. Stereomicroscope images of the microdroplets in the liquid paraffin were obtained with a SMZ-DM200 stereomicroscope (Optec, China) with a digital CCD camera to estimate the size in number-average diam-eters and coefficients of variation (CV, defined as the ratio of standard deviation to the mean) by ana-lyzing images of 100particles in liquid paraffin phase.
3. Results and discussion
3.1. CMC-Ph
3.1.1. FTIR spectrum
In Figure1a, the absorption bands at 1450, 1501, 1561 and 1611cm–1were ascribed to the benzene skeleton vibration. The peaks at 842, 1261 and 1386cm–1were attributed to the C–H out-of-plane bending vibration of benzene ring, C–O stretching vibration and O–H in-plane bending vibration of phenol, respectively. The absorption peak at 1642cm–1was associated to N–H scissoring vibra-tion of free amine. The broad association peak at 3423cm–1would be the stretching vibration of C–H, O–H and N–H, in which a hydrogen bond formed between a hydrogen atom and O–H group or N–H group. In FTIR spectrum of CMC-Ph (Figure1b, curve(2)), the absorption bands at 1045, 1323 and 1415cm–1were attributed to the –C=O stretching vibration, in-plane bending vibration of O–H and C–H scissoring vibration of methylene of CMC, respectively (Figure1b, curve(1)). The characteris-tic absorption bands of 4-hydroxybenzylamine were traced, including the C–H out-of-plane bending vibration of benzene ring (827cm–1), C–O strong stretching vibration of phenol (1257cm–1), benzene skeleton vibration (1504 and 1456cm–1) and N–H scissoring vibration of free amine (1644cm–1). The
band with a peak at 1579cm–1 was the IR absorption of the –O–stretching vibration of CMC (1592cm–1, Figure1b, curve(1)) and the benzene skeleton vibra-tion (1561 and 1611cm–1).
3.1.2. 1H NMR spectra
Figure2 illustrates 1H NMR spectra along with schematics of their chemical structures, on which proton assignments are indicated. 4-Hydroxybenzy-lamine (Figure2a) showed chemical shifts (") at 6.60 and 7.06ppm of aromatic protons (a) and (b), respectively, and at 3.81ppm of aliphatic protons (c). The spectra of CMC (Figure2b) and CMC-Ph (Figure2c) showed " of anomeric protons at 4.15 and 4.42ppm, and sugar ring protons between 3.11 and 3.99ppm for both macromolecules [28]. The signals at 7.21 and 6.84 ppm of CMC-Ph spectrum were attributed to the aromatic protons of 4-hydrox-ybenzylamine being grafted with CMC (CMC-g-Ph, 1a and 1b). The strong inductive effect being caused by the neighboring carbonyl groups decreased the electron density of the benzene ring, so that " of aromatic protons decreased compared with those of 4-hydroxybenzylamine (Figure2a, (a) and (b)). The signals at 1.79~2.02ppm (2a), 0.96~1.19ppm (2b) and 2.75ppm (2c) were ascribed to the byproduct being formed between CMC and EDC (CMC-EDC). EDC and phenolic groups of 4-hydroxybenzylamine reacted to form CMC-g-Ph-EDC, resulting in a change in proton shift of the aromatic protons at 7.51 and 7.35ppm (3a and 3b) [29].
3.1.3. Graft density of phenols
The CMC-Ph aqueous solution showed a specific absorbance with a peak at 275nm of 4-hydroxy-benzylamine. We also tested the dialysis solution at four days, the UV absorption was not detected, so that the UV absorption of the CMC-Ph solution would be ascribed to the grafted 4-hydroxybenzy-lamine. Based on the standard curve, the amount of the grafted 4-hydroxybenzylamine per 100units of CMC (grafting density) was calculated (Table1). It fell in the range of 17~23, and increased as M w of CMC increased. Usually, the flexibility of polymer increased with the increasing molecular weight, so that CMC with higher M w or M n was favorable to collide effectively with small molecules via chang-ing conformation, leading to a higher reaction prob-ability of CMC with 4-hydroxybenzylamine.
3.1.
4. Molecular weight
The molecular weight and the polydispersity (PI) of the molecular weight were also shown in Table1. M w, M n and PI of CMC-Ph were higher than those of CMC. The difference of molecular weight between CMC and CMC-Ph increased as the molecular weight of CMC increased, perhaps owing to a slight cross -linking between hydroxyl groups of 4-hydroxyben-zylamine and carboxyl groups of CMC under EDC/ NHS reactive system.
Figure 1.FTIR spectra of 4-hydroxybenzylamine(a), CMC(b-(1)) and CMC-Ph(b-(2))
3.1.5. Viscosity
Rheological behavior of the CMC-Ph solution with the different molecular weight has been determined by analyzing the influence of shear rate on viscos-ity. Flow curve was a straight line passing through the origin, and the stress increased lineally with the shear rate at 30°C, respectively (Figure3 (a2), (b2), (c2). An increase in the molecular weight produced an increase in the viscosity (Figure3). For example, the viscosity was 5.4, 14.8 and 25.5mPa·s, respec-tively for CMC10-Ph, CMC20-Ph and CMC30-Ph at 30°C. As the molecular weight of CMC-Ph increased, the intermolecular volume decreased and thus the molecular interaction of CMC-Ph increased. The CMC-Ph with high molecular weight possessed low ability to rearrange and move past each other, so
Figure 2.1H NMR spectra of 4-hydroxybenzylamine(a), CMC(b) and CMC-Ph(c) with protons assigned
that the internal resistance to flow increased. There-fore, the viscosity increased with the increasing molecular weight of CMC-Ph.
At 16°C, the viscosity of CMC 30-Ph decreased sig-nificantly with the increasing shear rate. When the shear rate was 215s –1, the viscosity was 9.9, 19.1 and 26.6mPa·s, respectively for CMC 10-Ph, CMC 20-Ph and CMC 30-Ph. In general, an increase in tempera-ture allows quicker molecules motion and thus less energy is needed to flow CMC-Ph solution, result-ing in a decrease in the viscosity. When the shear rate was 215s –1, the difference between viscosity meas-uring at 16 and 30°C was 4.45, 4.31 and 1.08mPa·s for CMC 10-Ph, CMC 20-Ph and CMC 30-Ph, respec-tively. The less difference of CMC 30-Ph was per-haps owing to the decreasing viscosity as the shear rate increased. As the shear rate was 215s –1, the viscosity ratio of CMC 30-Ph to CMC 10-Ph at 16°C was 2.7, which reached 4.7 when temperature went up to 30°C.
3.2. CMC-Ph microgels
Prior to the microfluidic preparation of CMC-Ph microgels, we examined the gelation of the disperse fluid as the presence of H 2O 2. The CMC-Ph gels were formed after a contact time of 1min. In the microfluidic device, the viscous disperse fluid was extruded into the immiscible continuous liquid flowing in the same direction. The disperse fluid flowed and snapped off at the orifice. H 2O 2in the continuous liquid surrounded the CMC-Ph droplets containing HRP. Thereafter, diffusion of H 2O 2from the continuous fluid to the disperse phase triggered the gelation reaction to bind the phenols groups.Because H 2O 2was separated from HRP, the enzy-matic reaction cannot occur before the droplets for-mation, thus avoiding the blockage of the inner opening. The concentration of H 2O 2in the continu-ous phase (0.82mmol/L) would not bring severe harmful effect on the encapsulated contents, but it was enough for gelation of the microdroplets. The CMC-Ph microgels were intact while immersed in DMEM for 40days. This diffusion-controlled cross-linking was very important for improving the integrity and encapsulation efficiency of micropar-ticles.
We prepared the CMC-Ph microdroplets with dif-ferent molecular weight while using the 1% CMC-Ph containing HRP (1mg/mL). As the flow rate of the disperse phase (Q d ) was fixed at 10μL/min, the effect of the flow rate of the continuous phase (Q c )on the radius of microdroplets was shown in Fig-ure 4a. The increased flow rate of the continuous phase produced a stronger shear force, thus resulted in a decreasing radius of the CMC-Ph microdroplets.
Figure 3. Viscosity of 1.0% CMC-Ph solution being meas-ured at 16°C: (a 1)CMC 30-Ph; (b 1)CMC 20-Ph;(c 1)CMC 10-Ph, and at 30°C: (a 2)CMC 30-Ph;(b 2)CMC 20-Ph; (c 2)CMC 10
-Ph
Figure 4.Dependence of flow rates on the size of the microdroplets obtained by using 1.0% CMC 10-Ph (triangle), CMC 20-Ph (circle) and CMC 30-Ph (square): (a)effect of Q c on the radius of microdroplets at a constant Q d (10μL/min);(b)effect of Q d on the radius of microdroplets at a fixed Q c (10mL/min)
When using a fixed Q c(10mL/min), the radius of the CMC-Ph microdroplets increased with an increas-ing flow rate of the disperse fluid (Figure4b). In general, the CMC-Ph solution with higher molecu-lar weight produced larger microdroplets due to higher viscosity.
3.3. Cell-laden CMC-Ph microgels
The injectable microsphere scaffolds should sup-port cells adhesion, migration, and proliferation, and more important, maintain the differentiated phenotype of the cells within the scaffold. The cell-laden microgels would facilitate gas exchange, nutrient diffusion, and waste metabolism. ATDC5 is a prechondrogenic stem cell line, and reproduces the differentiation stages of chondrocytes during endochondral bone formation [30]. The ATDC5-laden microgels being cultured up to 40days were shown in Figure5. The microgels presented round morphology that was very important for mechanical stability under the compressive forces in the body. The living cells (light dots) were distributed sepa-rately in the microgels (Figure5a). Some of the cell-laden microgels broke with the damaged border. The microgel did not maintain the round morphol-ogy any more (Figure5b). Some of the cells released from the broken microgels and can stick to the cell culture dishes at 40days of culturing (Figure5c), showing high viability.
4. Conclusions
4-Hydroxybenzylamine modified CMC with differ-ent molecular weight was synthesized through EDC/ NHS coupling agents. Uniform CMC-Ph micropar-ticles were obtained in the co-flowing microfluidic devices. The radius was tuned in the range of (100~ 500)μm by changing the flow rates of the disperse phase and the continuous phase, respectively. The
cells encapsulated in CMC-Ph microgels were still living at 40days of culturing. The microfluidic approach to the preparation of the cell-laden micro-gels will provide a potential method of fabricating scaffolds for tissue engineering, especially in the defect with an irregular-shape and/or a minimally invasive approach. The CMC-Ph microgels with the different molecular weight along with the different encapsulating content may also been used to pre-pare the injectable microsphere scaffolds, having a gradient mechanical property, a gradient encapsu-lating content, and a gradient releasing property. Acknowledgements
This study was financially supported by the Basic Research Project of China (2012CB619105), the National Natural Science Foundation of China (51072056, 51173053), Guang-dong Natural Science Foundation (9451063201003024), Guangdong Provincial Program for Excellent Talents in Universities, and Key Laboratory of Biomaterials of Guang-dong Higher Education Institutes of Jinan University.
Figure 5.Photographs of the cell-laden microgels up to 40days of culturing: (a)living cells distributed
separately at 40days; (b)broken cell-laden micro-
gels at 5days; (c)cells from the broken microgels
sticking to the dishes at 40days
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羧甲基纤维素钠的取代度的测定 羧甲基纤维素钠(CMC) 的分子取代度DS 是一个葡萄糖酐单元所加 入的氯乙酸钠摩尔数的平均值,所以我想你问的应该就是CMC的醚化度。 原理：将水溶性CMC酸化，变成不溶性的羧甲基纤维素，纯化后，用准确计量过的氢氧化钠将已知量的羧甲基纤维素重新转化为钠盐，再用盐酸标液滴定过量的碱。 试剂：95乙醇；80乙醇，无水甲醇；硝酸；盐酸标液(0.4mol/L)；氢氧化钠标液（0.4mol/L)；硫酸(9硫酸：2水）；二苯胺试剂（0.5g二苯胺溶于120ml 硫酸）；酚酞（1%乙醇溶液） 仪器：磁力加热搅拌器；烧杯（250ml）；锥形瓶（300ml）；玻璃过滤漏斗（40ml，孔径4.5-9um);105度烘箱。 操作：1，称4g样品于烧杯中，加75ml95%的乙醇，用吃力搅拌器充分搅拌成浆状物，在搅拌下加入5ml硝酸并继续搅拌1-2min，加热煮沸浆状物5min，停止加热，继续搅拌10-15min。 2，将上层清液倾过滤漏斗，用100-150ml的95%一乙醇转移沉淀至过滤漏斗，然后用60度的80%的乙醇洗涤沉淀至全部的酸被出去。 3，从过滤漏斗滴几滴滤液于白色点滴板上，加几滴二苯胺试剂，若蓝色，则表示有硝酸，需要进一步洗涤。 4，最后用少量的无水甲醇洗涤沉淀，继续抽滤至甲醇全除去，将烘箱加热至105度后关闭电原，然后将过滤漏斗放入烘箱，15min后打开箱门，排除甲醇蒸汽，关闭烘箱门，接通电源，在105度干燥3个小时，然后冷却0.5 小时。 计算,(方法你应该看明白了吧，计算我明天告诉你，要下班了，打字好累啊）样品中羧甲基纤维素钠的醚化度： A=(BC-DE)/F；醚化度=0.162A/(1-0.058A) 式中 A--中和1g羧甲基纤维素所消耗的氢氧化钠的豪摩尔数； B--加入的氢氧化钠标准滴定溶液的体积，ml； C--氢氧化钠标液的浓度，mol/L D--滴定过量的氢氧化钠所用的盐酸标液的滴定体积，ml； E--盐酸标液的浓度，mol/L F--用于测定酸式羧甲基纤维素的质量，g。 0.162--纤维素的失水葡萄糖单元的豪摩尔质量，g/mmol; 0.058--失水葡萄糖单元中的一个羟基被羧甲基取代后，失水葡萄糖单元的豪摩尔质量的净增值，g/mmol. 终于搞定了，不过还有几个控制要点，需要的话再告诉你！！ 重复性 两次测定结果差值不应该超0.02的醚化度单位
山东聊城阿华制药有限公司 SOP-FPS 25 00 Shandong Liaocheng Ehua Medicine CO., LTD 页码：1/2 1．目的 本程序是为羧甲基纤维素钠产品的化学及微生物检验而制定。 2． 范围 本程序规定了羧甲基纤维素钠产品的质量标准、检验操作法。 3． 引用标准 化学药品地方标准上升国家标准（第五册） 标准号 WS-10001-(HD-0486)-2002 《中国药典》2005年版二部； 4． 质量标准和检验操作法 4.1 [主要成分]：本品为羧甲基纤维素的钠盐。按干燥品计算，含钠（Na ）应为6.5%~8.5%。 4.2 [性状] 本品为白色或微黄色纤维状粉末；无臭、无味、具吸湿性。 本品在水中溶解成粘稠胶体。在乙醇、乙醚或氯仿中不溶。 4.3 [鉴别] 取本品1g ，加温水50ml,搅拌使扩散均匀，继续搅拌直至生成乳胶体溶液，冷却至室温，供以下试验用。 （1） 取上述溶液30ml ，加盐酸3ml ，即产生白色沉淀。 （2）取以上剩余溶液，加等容积氯化钡试液，即生成白色沉淀。 （3）试验（1）项下的溶液滤过，滤液应显钠盐的鉴别反应（中国药典2005年版二部附录Ⅲ）。 4.4 [检查] 4.4.1干燥失重：取本品0.5g ，精密称定，在105℃干燥，至恒重，减少重量不得过10%（中国药典2005年版二部附录Ⅷ L ）。 4.4.2酸碱度：本品的1%水溶液，依法检查（中国药典2005年版二部附录ⅥH ），pH 值应为6.5~8.0。 4.4.3黏度：精密称取本品2g （以干燥品计），渐次分批加入贮有约90ml 温水的广口瓶内，迅速搅拌至粉末湿透，冷却至室温，加入足够的水使混合物为100g ，静置、时时搅拌，直至完全扩
羧甲基纤维素钠 羧甲基纤维素钠（CMC），是纤维素的羧甲基化衍生物，又名纤维素胶，是最主要的离子型纤维素胶。CMC 于1918 年由德国首先制得，并于1921 年获得专利而见诸于世，此后便在欧洲实现商业化生产。当时只为粗产品，用作胶体和粘结剂。1936～1941 年，对CMC 工业应用的研究相当活跃，并发表了几个具有启发性的专利。第二次世界大战期间，德国将CMC 用于合成洗涤剂。CMC 的工业化生产开始于二十世纪三十年代德国IG Farbenindustrie AG。此后，生产工艺、生产效率和产品质量逐步有了明显的改进。1947 年，美国FDA根据毒物学研究证明：CMC 对生理无毒害作用，允许将其用于食品加工业中作添加剂，起增稠作用。CMC 因具有许多特殊性质，如增稠、粘结、成膜、持水、乳化、悬浮等，而得到广泛应用。近年来，不同品质的CMC 被用于工业和人们生活的不同领域中。 1 CMC 的分子结构特征 纤维素是无分支的链状分子，由D-吡喃葡萄糖通过β-(1→4)-苷键结合而成。由于存在分子内和分子间氢键作用，纤维素既不溶于冷水也不溶于热水，这使它的应用受到了限制。纤维素在碱性条件下溶胀，如果通过特殊的化学反应，用其它基团取代葡萄糖残基上C2、C3及C6位的羟基即可得到纤维素衍生物，其中有35％的纯纤维素被转化为纤维素酯（25％）和纤维素醚（10％）。 CMC 是纤维素醚的一种，通常是以短棉绒（纤维素含量高达98％）或木浆为原料，通过氢氧化钠处理后再与氯乙酸钠（ClCH2COONa）反应而成，通常有两种制备方法：水媒法和溶媒法。也有其他植物纤维被用于制备CMC，新的合成方法也不断地被提出来。 CMC 为阴离子型线性高分子。构成纤维素的葡萄糖中有 3 个能醚化的羟基，因此产品具有各种取代度，取代度在0.8 以上时耐酸性和耐盐性好。商品CMC 有食品级及工业级之分，后者带有较多的反应副产物。CMC 的实际取代度一般在0.4～1.5 之间，食品用CMC 的取代度一般为0.6～0.95，近来修改后的欧洲立法允许将DS 最大为 1.5 的CMC 用于食品中；取代度增大，溶液的透明度及稳定性也越好。 取代度（Degree of Substitution，DS）决定了CMC 的性质，而取代基的分布也会对产品性质产生影响。DS 和取代基分布的准确测定是优化反应条件、确定结构性质关系的先决条件。羧甲基可以在葡萄糖单元（AGU）的2、3、6 位上发生取代，有八种可能的结构单元（无取代；C2；C3；C6；C2、C3；C2、C6；C3、C6；C2、C3、C6）构成了高分子链。不同高分子链中重复单元的分布也可能是不同的。 1.1 DS 的测定 测定CMC 取代度的一种常用方法是滴定法，把CMC 钠盐转化为酸的形式，反之亦然。把CMC 钠盐分散在乙醇和盐酸中，用已知摩尔浓度的氢氧化钠溶液滴定。还有一种反滴定法，一般是测定CMC 取代度的标准方法：把氢氧化钠加入到未知量的CMC 酸中，反滴定过量的氢氧化钠来计算DS。电导滴定法也可以较准确地测定DS，曾晖扬等提出了红外光谱法，并可直观地大致判断出样品的纯度，以决定是否需要对样品进行提纯精制。 钠的确定比较简单，但是需要满足一些先决条件，CMC 需要完全转化为钠盐的形式，而且在合成中带来的NaCl 及氯乙酸钠需要完全除去。后一种问题一般是通过透析的方法解决，但是这样也存在一个问题，对于部分取代度高而分子量低的分子容易流失，这样会带来误差。 CMC 可以与盐离子如铜离子作用生成沉淀，反滴定过量的铜离子也可以确定CMC 的取代度。对于CMC，用硝酸铀酰溶液使之沉淀，然后将其燃烧测定得到的氧化铀，也是一种测定取代度的有效方法。 除此以外还有其他用于测定CMC 取代度的方法，如核磁、毛细管电泳等。液相核磁测
羧甲基纤维素 MSDS Carboxymethyl cellulose 羧甲基纤维素性质、用途与生产工艺 含量分析 羧甲基纤维素钠的百分含量按100减去下述氯化钠和乙醇酸钠的百分含量而得。 氯化钠含量精确称取试样约5g，移人一250m1烧杯，加水50ml和30%过氧化氢5ml，在蒸汽浴上加热20min，偶尔搅拌一下，至完全溶解。冷却，采用硫酸银和硫酸汞一硫酸钾电极，并不停搅拌，加水100ml和硝酸10ml，然后用0.05mol/L硝酸银滴定至电位终点。按下式计算试样中的氯化钠百分含量： (584．4Vc)/(100-6)ω其中，V和c分别为所耗硝酸银的体积(m1)和浓度(mol/L)；6为所测得的干燥失重；ω为试样质量(g)；584.4为氯化钠的分子量。 乙醇酸钠含量准确称取试样约500mg，移入一100ml烧杯，先经5ml冰乙酸随后用5ml 水湿润，然后用玻棒搅至溶液状(一般约需15min)。在搅拌下缓慢加入丙酮50ml，然后加氯化钠1g，搅拌数分钟使羧甲基纤维素钠全部沉淀。经一已用少量丙酮湿润过的软质粗孔滤纸过滤，将滤液收集于一100ml容量瓶中，另用30ml丙酮将滤渣移人滤纸并淋洗滤渣，然后用丙酮稀释，定容后混匀。 按下述制备标准液：准确称取室温下干燥器中过夜的乙醇酸100mg，移人一100ml容量瓶中，用水溶解，定容后混匀。该液应在30天之内使用。将该液1.0.、2.0、3.0和4.0m1分别移入四只100ml容量瓶中，分别加水至约5ml，然后加冰乙酸5ml，并用丙酮稀释、定容。 取前述试样液2.0ml和各标准液各2.0ml，分别移入五只25ml容量瓶中，另配一空白瓶，内含由冰乙酸和水各占5%的丙酮液2.0ml。将各容量瓶不加盖在沸水浴上保持 20min以除去丙酮，取下，冷却。每只瓶中各加2，7-二羟萘试液(TS-85)5.0ml，强力混合后再加15ml，再强烈混合。取小片铝薄盖口。将容量瓶垂直放入沸水浴中保持 20min，然后取出，冷却，用硫酸定容后混匀。 用一适当的分光光度计，以空白液为对比，在540nm处测定各液的吸光度，按标准液吸光度绘制标准曲线，然后根据标准曲线和试样的吸光度求出试样中乙醇酸的质量(mg)叫，然后按下式求出试样中 毒性 ADI不作特殊规定(FAO/WHO，2001)。 LD50(大鼠，经口)27g/kg。 GRAS(FDA，§182．1745，2000)。 使用限量
羧甲基纤维素钠检测方法 1.性状：本品为白或类白色的粉末，粒状或纤维状物质，无臭。 2.鉴定试验 本品0.5g溶在50mL水中搅拌，每次加少量，在60～70℃时时搅拌，同时加温20分钟，做成均匀溶液，冷却后为检液，进行下述试验。 1)在检液中加水稀释5倍，在其1滴上加铬变酸试液0.5mL，水浴加热10分钟呈现红紫 色。 2)在5mL检液中加入丙酮10mL，充分振荡混合产生白色的絮状沉淀。 3)在5mL检液中加入1mL硫酸酮试液，混合振荡产生淡蓝色的絮状沉淀。 4)把本品灰化得的残留物，呈现钠盐的常规反应。 3. 纯度试验 （1）透明度把本品2g分批每次少量加入200mL水中，边搅拌边加入。在60～70℃下，不断振荡混合并加温20分钟，制成均匀的溶液，冷却后作为检液。然后再高250mm、内径25mm、厚2mm的玻璃圆筒底部用2mm厚的优质玻璃板密封作为外管。再把高300mm、内径15mm、厚2mm的玻璃圆筒的底部用厚2mm的优质玻璃板密封作为内管，把检验液注入外管中，注意防止气泡进入，这样做成的两个密封套管，然后将两管放在一张划有宽1mm、间隔1mm的15条平行线的白纸上，上下活动内管，是外管试液流入内管的管底，从上部用肉眼观看，到内管下端的黑线不能辨识为止，测定溶液这时的高度，把这操作重复三次取的平均值，和用标准溶液进行同样的操作得的平均值比较，前者不应小于后者。 标准液（测定透明度用）在0.005mol/L硫酸5.5mL中加稀盐酸1mL醇5mL及水定容成50mL，再加氯化钡试液2Ml,充分混合震荡，放置10分钟，用时荡混均匀再用。 （2）酸碱性在纯度试验（1）中得的检液的PH值，用玻璃电极法测定6-8. （3）氯化物本品0.1g加水20ML及双氧水0.5ML，水浴加热20min后，冷却，加水成100ML，用滤纸过滤，取滤液25ML加稀硝酸6ML，作为检液，进行氯化物的常规试验，其量应在0.01MO1/L盐酸0.45ML的对比量以下。 （4）硫酸盐取在纯度试验（3）中得到的滤液20ML，加稀盐酸1ML，以此作为检液进行硫酸盐的常规试验，其量在0.005MO1/L硫酸0.4ML的对应量以下。
目录 摘要 (1) 关键词 (1) 一、生产原料纤维素的来源 (1) 二、羧甲基纤维素（CMC）性质 (2) 三、羧甲基纤维素（CMC）生产工艺 (2) 四、羧甲基纤维素用途 (4) 五、羧甲基纤维素（CMC）国内外生产及利用现状 (5) 六、羧甲基纤维素（CMC）发展方向 (5) 参考文献 (5) 羧甲基纤维素的生产与应用 摘要：羧甲基纤维素（CMC）,是以纤维素为原料合成的纤维素醚类产品，有着良好的化学和物理性能，在医药、陶瓷、食品添加剂、造纸、建材、涂料等方面也有着广泛的应用前景。本文将综述羧甲纤维素的生产原料来源、性质和国内外生产应用现状以及发展前景。，其中重点介绍羧甲基纤维素（CMC）的合成工艺和具体的应用。 关键词：羧甲基纤维素、生产工艺、应用、发展方向。 Abstract: Cellulose is composed of macromolecular polysaccharide, is a kind of important natural polymer, not only to the health of human body, but also has a broad prospect of application in medicine, ceramics, food additives, paper making, building materials, paint also. This paper will review the source of cellulose and its application, which mainly introduces CMC synthesis principle and application status at home and abroad, as well as the development foreground. Key words: Cellulose, CMC, Composition principle, Application, Development. 一、生产原料纤维素的来源 经过多年的研究和发展，目前可以用于合成羧甲基纤维素的原料有精制棉短绒、地脚棉、甘蔗渣、秸秆及稻草等。但生产工艺对纤维素原料中а纤维素含量的要求很高，虽然精制棉短绒价格相对其他材料昂贵，数量相对较少。但以上这些原材料中精制棉短绒的棉纤维含量高达90%以上，精制棉短绒生产出来的羧甲基纤维素比其他原材料所生产出来的产品性能更优越，故比其他原材料更是符合工业化生产。因而，目前世界上用于生产的羧甲基纤维素的主要原材料是精制棉短绒。
项目特高粘度高粘度中粘度 外观白色或微黄色纤维状粉末 粘度（2%水溶液，mpa·s）1200 800~1200 300~800 钠含量（Na,%） 6.5~8.5 6.5~8.5 6.5~8.5 PH值 6.0~8.5 6.0~8.5 6.0~8.5 干燥减量（%）≤10.0 10.0 10.0 氯化物（以CI计，%）≤ 1.8 1.8 1.8 重金属（以Pb计，%）≤0.002 0.002 0.002 铁（Fe,%）≤0.03 0.03 0.03 砷（As,%）≤0.0002 0.0002 0.0002
CMC可用于配制水溶性胶粘剂，粘接纸张，织物等。也可用作水溶性胶粘剂的增稠剂。贮存于阴凉、干燥的库房内，防潮、防热。 二、相关新闻： 【1】羧甲基纤维素钠黏度标准尚需完善 药用辅料是生产药物制剂的必备材料，近年我国制药工业的发展速度较快，国家对药品质量的标准与要求也在不断提高与完善，药用辅料在药品生产及剂型开发中的重要性正越来越多地被人们所认识。 目前市场上常用的药用辅料品种较多，主要包括羟丙纤维素、羟丙甲纤维素、微晶纤维素、羧甲基纤维素钠、羧甲淀粉钠、各种型号的树脂以及包衣粉等，这些药用辅料作为崩解剂、粘合剂及包衣材料被广泛地应用于药生产的各个方面。随着药品生产企业对新药品剂型开发重视度的提高，他们对药用辅料的质量要求也越来越严格。但就现有的国家药品标准来看，有关质量标准的规定还很不完善，从而极大地制约了药品质量的提高及新品种的研发。 以安徽淮南山河药用辅料有限公司生产的羧甲基纤维素钠为例，技术人员通过对该种药用辅料黏度规定的研究与分析，发现现有质量标准规定存在不完善之处，主要表现在如下三个方面。 一、黏度计的使用型号及转子转速未作规定。
我们都知道羧甲基纤维素钠属于天然纤维素改性，可以称它为“改性纤维素”。目前在食品、化工、石油等行业中都可以见到它，但是对于其合成的工艺大部分应该不是很了解，通过下文或许可以找到答案。 具体的生产工艺为：以纤维素为原料，采用两步法制备CMC-Na。先是纤维素的碱化过程，纤维素与氢氧化钠反应后生成碱纤维素，然后是碱纤维素与氯乙酸反应生成CMC-Na，称为醚化反应。 Cell-OH+NaOH->Ce11 O-Na++H20 之后碱纤维素与氯乙酸反应生成CMC，反应方程式如下： ClCH2COOH+NaOH->C1CH2COONa+H20 Ce11 0-Na++C1CH2C00-->Ce11-OCH2C00-Na 该反应体系必须为碱性。该过程属于Williamson醚合成法。反应机制为亲核取代。反应体系属碱性，在水的存在条件下伴随一些副反应，如羟乙酸钠、羟乙酸等副产物生成，由于副反应的存在，会增加碱和醚化剂的消耗，进而降低醚
化效率；同时，副反应中会生成羟乙酸钠、羟乙酸和更多的盐类杂质，造成产物的纯度和性能降低。想要抑制副反应，不仅要合理用碱，控制水系用量、碱的浓度和搅拌方式，以碱化充分为目的，同时还要考虑到产品对黏度和取代度的要求，综合考虑搅拌速度、温度控制等因素，提高醚化速率，抑制副反应发生。 按醚化介质的不同，CMC-Na的工业生产可分为水媒法和溶媒法两大类。以水作为反应介质的方法叫做水媒法，用于生产碱性中低档CMC-Na。以有机溶剂作为反应介质的方法，叫做溶媒法，适用于生产中高档CMC-Na。这两种反应都属于捏合法工艺，下面来详细了解一下： （一）水媒法 是一种较早的工业生产工艺，该方法是将碱纤维素与醚化剂在游离碱和水的条件下进行反应。碱化和醚化过程中，体系中没有有机介质。水媒法设备要求较为简单，投资少、成本低。缺点是缺乏大量液体介质，反应产生的热量使温度升高，加快了副反应的速度，导致醚化效率低，产品质量差等。该方法用于制备中低档CMC-Na产品，如洗涤剂、纺织上浆剂等。 （二）溶媒法
化学化工学院材料化学专业实验报告 实验名称：羧甲基纤维素的合成 年级：10级材料化学日期：2012.10.25 姓名：学号：同组人： 一、预习部分 1、羧甲基纤维素简介： 羧甲基纤维素是纤维素的羧甲基团取代产物。根据其分子量或取代程度，可以是完全溶解的或不可溶的多聚体，后者可作为弱酸型阳离子交换剂，用以分离中性或碱性蛋白质等。羧甲基纤维素可形成高粘度的胶体、溶液、有粘着、增稠、流动、乳化分散、赋形、保水、保护胶体、薄膜成型、耐酸、耐盐、悬浊等特性，且生理无害，因此在食品、医药、日化、石油、造纸、纺织、建筑等领域生产中得到广泛应用。 2、羧甲基纤维素的性质： 纤维素的羧甲基团取代产物。根据其分子量或取代程度，可以是完全溶解的或不可溶的多聚体，后者可作为弱酸型阳离子交换剂，用以分离中性或碱性蛋白质等。羧甲基纤维素又称作羧甲基纤维素钠。羧甲基纤维素钠(CMC)分子结构如下图所示： 由德国于1918年首先制得，并于1921年获准专利而见诸于世。此后便在欧洲实现商业化生产。当时只为粗产品，用作胶体和粘结剂。1936～1941年，羧甲基纤维素钠的工业应用研究相当活跃，发明了几个相当有启发性的专利。第二次世界大战期间，德国将羧甲基纤维素钠用于合成洗涤剂。Hercules公司于1943年为美国首次制成羧甲基纤维素钠，并于1946年生产精制的羧甲基纤维素钠产品，该产品被认可为安全的食品添加剂。上世纪七十年代我国开始采用，九十年代开始普遍使用。是当今世界上使用范围最广、用量最大的纤维素种类。 物理性质：羧甲基纤维素钠（CMC）属阴离子型纤维素醚类，外观为白色或微黄色絮状纤维粉末或白色粉末，无嗅无味，无毒；易溶于冷水或热水，形成具有一定粘度的透明溶液。溶液为中性或微碱性，不溶于乙醇、乙醚、异丙醇、丙酮等有机溶剂，可溶于含水60%的乙醇或丙酮溶液。有吸湿性，对光热稳定，粘度随温度升高而降低，溶液在PH值2～10稳定，PH低于2，有固体析出，遇多价金属盐也会反应出现沉淀。PH值高于10粘度降低。变色温度227℃，炭化温度252℃，2%水溶液表面张力71mn/n。 化学性质：有羧甲基取代基的纤维素衍生物，用氢氧化钠处理纤维素形成碱纤维素，再与一氯醋酸反应制得。构成纤维素的葡萄糖单位有3个可被置换的羟基，因此可获得不同置换度的产品。平均每1g干重导人1mmol羧甲基者，在水及稀酸中不溶解，但能
摘要 羧甲基纤维素钠（简称CMC）是以精制短棉为原料而合成的一种阴离子型高分子化合物。分子量6400（±1000），具有优良的水溶性与成膜性，广泛应用于石油、日化、轻工、食品、医药等工业中，被誉为“工业的味精”。1989年4月化工部曾将CMC-Na 列为“新领域精细化工‘八五’规划产品”。 CMC-Na生产发展到今天，合成方法主要有两种，一种是水煤直接法（喷碱法），另一种是采用有机溶媒体的溶媒法，由于后者具有用碱量少，醚化时间短，醚化剂利用率高等特点，因此目前已被广泛采用。然而目前国内使用的CMC-Na普遍存在着合格率较低，成本大幅度上升，新产品开发缓慢等问题。 衡量CMC-Na质量的主要指标是取代度（DS）和粘度，一般来说，DS不同，则CMC-Na 的性质也不同；取代度增大，溶液的透明度及稳定性也越好。据报道，CMC-Na取代度在0.7-1.2时透明度较好，其水溶液粘度在pH为6-9时最大，为保证其质量，除选择醚化剂外，还必须考虑影响取代度和粘度的一些因素，例如碱与醚化剂之间的用量关系、醚化时间、体系含水量、温度、pH值、溶液浓度等。 本文目的旨在降低成本，提高质量，通过从几大因素——碱化温度、醚化温度、碱化时间、醚化时间、碱的浓度、醚化剂配比分别合成，并检验各种产品的性能，进而得出合成CMC-Na的最佳工艺条件。 关键词：溶媒法；粘度；醚化剂；最佳工艺条件
Abstract Sodium carboxymethyl cellulose （CMC）is an anionic polymer compound composed by refine short cotton, whose molecular weight is 6400（±1000）, highly water-soluble and good film-forming property. It is widely used in the industries of petroleum, daily chemicals, light industry, food and pharmaceuticals, which is renowned as the “Aginomoto of Industries”. The Ministry of Chemical Industry ranked CMC-Na as the project product in fine chemical industry of the “Eighth Five-year Plan”. So far, two synthetic methods of CMC-Na have been developed, one of which is direct compounding of coal and water (Alkali Spraying) and the other is organic solvent. The lower alkali charge, shorter etherification process and high-efficient utilization of etherifying agent, the latter method is adopted widely. But lower quality, increasing production cost and slow development of new product are the common problems resided in the domestic CMC-Na. The main indexes to assess the quality of CMC-Na are degree of substitution (DS) and viscosity. Generally, DS determines the property of CMC-Na; the more the degree of substitution, the better the transparency and stability of the solution. It is said the transparency of CMC-Na is higher when the DS is in 0.7-1.2, and the viscosity is at the highest when pH is 6-9. To ensure the quality, apart from etherifying agent, the factors affecting the DS and viscosity shall also be taken into account, such as the relationship between alkali and the amount of etherifying agent, how long etherification lasts, content of water in the system, temperature, pH and concentration of solution.This thesis aims to seek ways to reduce the production cost and improve the quality of CMC-Na. The common factors, such as temperature of alkalization and etherification, time for alkalization and etherification, concentration of alkaline and ration of etherifying agent are respectively used to synthesize CMC-Na in order to find out the best processing conditions for synthesis of CMC-Na. Key word：organic solvent ；viscosity ；etherifying agent ；the best processing conditions for synthesis
主要有效成分羧甲基纤维素钠级别陶瓷级 品牌杨森化工，陶隆化学有效物质含量 95（％） 产品规格25kg/包执行标准企业标准 主要用途釉用cas 无 羧甲基纤维素钠（cmc） 前言： cmc是一种水溶性高分子纤维素，由纸浆(α-cellouse)与单氯乙酸钠经醚化后之产品。应用于陶瓷釉浆中主要作用在于调整釉浆粘度及流变性，改善坯釉结合性能，提高釉面强度及表面张力，增强釉料的保水性，防止开裂及印刷断裂，同时减少釉干燥后收缩，增加生釉强度，使之不易与坯体剥落，此外在施釉后干燥均匀，因而形成致密坚实之釉面，使烧成后之瓷砖更平整光滑。 一、产品型号、应用及特性 产品型号应用范围cmc特性 粘度 （mpa.s）取代 度 备 注 cmc-500陶瓷渗花釉分子链短，透明度高，渗透性好400~500≥0.90 cmc-1400日用瓷、卫浴釉料粘接、悬浮、保水、解凝、流变性等均极佳1000~1400≥1.20 cmc-2500陶瓷印花釉溶解性及透明度高，流动性、分散性、透网性 好，不塞网，溶液稳定性高 2500~3000≥0.95 颗 粒 状 cmc-3000陶瓷印花釉2800~3300≥0.95 cmc-1200陶瓷釉料、印花釉调节釉浆粘度,良好的流变性，提高釉面强度 及保水性，增强釉面的平滑度，避免因施釉后 坯体开裂及印刷断裂 1100~1400≥0.90 cmc-6000陶瓷釉料、印花釉5500~6500≥0.90 cmc-3500陶瓷釉料在釉浆中起粘接、悬浮、保水、解凝作用，流 变性稍差。 3300~3800≥0.85 cmc-4000陶瓷釉料流动性好，电荷密集，用量少，提高釉浆稳定 性、平滑性、黏附性，在釉浆中起粘接、悬浮、 保水、解凝作用。 3500~4000≥0.90 备注以上粘度为2%溶液在30℃时,用ndj-1粘度计测定
实验8 羧甲基纤维素的合成 一、实验目的 了解纤维素的化学改性、纤维素衍生物的种类及其应用 实验原理 天然纤维素由于分子间和分子内存在很强的氢键作用，难以溶解和熔融，加工成型性能差，限制了纤维素的使用。天然纤维素经过化学改性后，引入的基团可以破坏这些氢键作用，使得纤维素衍生物能够进行纺丝、成膜和成型等加工工艺，因此在高分子工业发展初期占据非常重要的地位。纤维素的衍生物按取代基的种类司·分为醚化纤维素(纤维素的羟基与卤代烃或环氧化物等醚化试剂反应而形成醚键)和酯化纤维素(纤维素的羟基与羧酸或无机酸反应形成酯键)。羧甲基纤维素是一种醚化纤维素，它是经氯乙酸和纤维素在碱存在下进行反应而制备的。 由于氢键作用，纤维素分子有很强的结晶能力，难以与小分子化合物发生化学反应，直接反应往往得到取代不均一的产品。通常纤维素需在低温下用Na0H溶液进行处理，破坏纤维素分子间和分子内的氢键，使之转变成反应活性较高的碱纤维素，即纤维素与碱、水形成的络合物。低温处理有利于纤维素与碱结合，并可抑制纤维素的水解，碱纤维素的组成将影响到醚化反应和醚化产物的性能。纤维素的吸碱过程并非是单纯的物理吸附过程，葡萄糖单元的羟基能与碱形成醇盐。除碱液浓度和温度外，某些添加剂也会影响到碱纤维素的形成，如低级脂肪醇的加入会增加纤维索的吸碱量。 醚化剂与碱纤维素的反应是多相反应，醚化反应取决于醚化剂在碱水溶液中的溶解和扩散渗透速度，同时还存在纤维素降解和醚化剂水解等副反应。碘代烷作为醚化剂，虽然反应活性高，但是扩散慢、溶解性能差：高级氯代烷也存在同样问题。硫酸二甲酯溶解性好，但是反应效率低，只能制备低取代的甲基纤维素。碱液浓度和碱纤维素的组成对醚化反应有很大影响，原则上碱纤维素的碱量不应超过活化纤维素羟基的必要量，尽可能降低纤维素的含水量也是必要的。 醚化反应结束后，用适量的酸中和未反应的碱以终止反应，经分离、精制和干燥后的得到所需产品。 羧甲基纤维素是一种聚电解质，能够溶于冷水和热水中，广泛应用于涂料、食品、造纸 和日化等领域。 三、化学试剂和仪器 化学试剂：95％异丙醇，甲醇，氯乙酸，氢氧化钠，微晶纤维素或纤维素粉，盐酸。 反应监测：0．1mol／L标准NaOH溶液，0．1mol／L标准盐酸溶液，酚酞指示剂，AgNO3溶液，PH试纸。 仪器设备：机械搅拌器，三口烧瓶，酸式滴定管，温度计，锥形瓶，通氮装置，研钵。四、实验步骤 纤维素的醚化：将10-20份95％异丙醇和1.64份45％NaOH水溶液加入到装有机械搅拌器的三口烧瓶中，通入氮气并开动搅拌，缓慢加入1份微晶纤维素(6g)，于30℃剧烈搅拌40 min，即可完成纤维素的碱化。将氯乙酸溶于异丙醇中，配制成75％的溶液，向三口瓶中加入1.14份该溶液。充分混合后，升温至75℃反应40 min。冷却至室温，用10％的稀盐酸中和pH 为4，用甲醇反复洗涤除去无机盐和未反应的氯乙酸。干燥，粉碎，称重，计算取代度。五、扩展部分 取代度的测定：用70％的甲醇溶液配制lmol／L的HCl／CH3OH溶液，取0.5 g醚化纤维素
微晶纤维素-羧甲基纤维素钠标准 Weijing xian wei su-suo jia ji xian wei su na Microcrystalline Cellulose and Carboxymenthylcellulose Sodium (进口药品注册标准JX20040038) 本品是由微晶纤维素和羧甲基纤维素钠组成的胶状混合物。按干燥品计算，含羧甲基纤维素钠应为标示量的75.0%~125.0%。 【性状】本品为白色或类白色或微黄色的粉末，无臭，无味。 【鉴别】（1）取本品6.0g，称定，置搅拌器中，加水300ml，搅拌5分钟（18000rpm）。应出现白色不透明的分散液，静置后不分散。 （2）取鉴别（1）的分散液，滴几滴于氯化铝溶液（1→10）中，均应形成白色不透明的小球，静置后不分散。 （3）取碘试液3ml，加入鉴别（1）的分散液中，应不产生蓝色或蓝紫色。 【检查】黏度（在室温20±1℃下测定） 取本品，以干燥品计算，按本品水性分散液的标示浓度，制备600g的分散液，以旋转式黏度计测定（中国药典2000年版二部附录ⅥG第二法）。 测定法精密称取适量的水，置圆柱形层析缸［高度x直径（180×83mm）］内，置入棒状机械搅拌器（棒状机械搅拌器为德国制造，型号：T25BS4，固定转速为18000rpm），启动搅拌器，使水旋转，停止搅拌，移出搅拌器，在水仍在旋转时小心加入精密称取的本品适量，并立即计时，再置入搅拌器，棒头距缸底约25mm，15秒钟时，立即启动搅拌器（注意，样品不能粘住搅拌棒和缸壁，可上下约10mm移动或慢慢转动层析缸，必要时可用玻棒帮助消除粘住的样品）准确计时2分钟，停止搅拌，迅速将层析缸移离搅拌器，把适当的转子（带保护框）降入分散液中并调节转子的刻度至分散液的平面（Brookfield DV-Ⅱ+黏度计和1号转子适用），停止搅拌30秒钟时，启动旋转黏度计，在20rmp的速度下，测得读数应在全刻度的10~90%之间，在旋转30秒钟时立刻读取数值。重复测定三次，计算平均黏度，每次测定值与平均值之差不得超过平均值的±3%。黏度应为表示黏度的60.0%~140.0%。 酸碱度取黏度检查项下的分散液，依法测定（中国药典2000年版二部附录ⅥH），PH值为6.0~8.0。 干燥失重取本品，在105℃干燥3小时，减失重量不得过8.0%（中国药典2000年版二部附录ⅧL）。
羧甲基纤维素钠 百科名片 羧甲基纤维素钠，（又称:羧甲基纤维素钠盐，羧甲基纤维素，CMC，Carboxymethyl ，C ellulose Sodium,Sodium salt of Caboxy Methyl Cellulose）是当今世界上使用范围最广、用量最大的纤维素种类。 [编辑本段] 诞生 羧甲基纤维素钠(CMC)分子结构 由德国于1918年首先制得，并于1921年获准专利而见诸于世。此后便在欧洲实现商业化生产。当时只为粗产品，用作胶体和粘结剂。1936～1941年，羧甲基纤维素钠的工业应用研究相当活跃，发明了几个相当有启发性的专利。第二次世界大战期间，德国将羧甲基纤维素钠用于合成洗涤剂。Hercules公司于1943年为美国首次制成羧甲基纤维素钠，并于1946年生产精制的羧甲基纤维素钠产品，该产品被认可为安全的食品添加剂。上世纪七十年代我国开始采用，九十年代开始普遍使用。是当今世界上使用范围最广、用量最大的纤维素种类。 [编辑本段] 性状 羧甲基纤维素钠(CMC)外观
本品为纤维素羧甲基醚的钠盐，属阴离子型纤维素醚，为白色或乳白色纤维状粉末或颗粒，密度0.5-0.7/c㎡，几无臭、无味，具吸湿性。易于分散在水中成澄明胶状液，在乙醇等有机溶媒中不溶。1％水溶液pH为6.5～8.5，当pH＞10或＜5时，胶浆粘度显著降低，在pH7时性能最佳。对热稳定，在20℃以下粘度迅速上升，45℃时变化较慢，80℃以上长时间加热可使其胶体变性而粘度和性能明显下降。 [编辑本段] 工艺 CMC通常是由天然纤维素与苛性碱及一氯醋酸反应后制得的一种阴离子型高分子化合物，分子量6400(±1 000)。主要副产物是氯化钠及乙醇酸钠。CMC属于天然纤维素改性。目前联合国粮农组织(FAO)和世界卫生组织(WHO) 已正式称它为“改性纤维素”。 [编辑本段] 质量 衡量CMC质量的主要指标是取代度(DS)和纯度。一般DS不同则CMC的性质也不同；取代度增大，溶解性就增强，溶液的透明度及稳定性也越好。据报道，CM C取代度在0.7～1.2时透明度较好，其水溶液粘度在pH值为6～9时最大。为保证其质量，除了选择醚化剂外，还必须考虑影响取代度和纯度的一些因素，例如碱与醚化剂之间的用量关系、醚化时间、体系含水量、温度、DH值、溶液浓度及盐类等。[编辑本段] 现状 为了解决原料（棉短绒制成的精制棉）来源之不足，近几年来我国一些科研单位与企业共同合作，综合利用稻草、地脚棉(废棉)、豆腐渣等试制生产CMC获得成功，生产成本大大下降，这样为CMC工业生产开辟了一条新的原料来源途径，实现资源的综合利用。一方面降低生产成本，另一方面CMC又往更高精细方向发展。目前，CMC的研究与开发主要着重现有生产技术的改造与制造工艺的革新，以及具有独特性能的CMC新产品，如国外研制成功并已普及应用的“溶媒-多元弱极性溶剂法”[1]工艺，生产出具有高稳定性能的新型改性CMC，由于取代度较高，取代基分布更为均匀，使其可以应用在更为广阔的工业生产领域和复杂的使用环境，满足更高的工艺要求。国际上把这种新型改性CMC又称作“聚阴离子纤维素（简称PAC，Poly anioni c cellulose）”。 (参考资料：https://www.doczj.com/doc/733124517.html,/view/2181425.htm) [编辑本段] 应用
Q/09FYT 山东一滕化工有限公司企业标准 Q/09FYT002-2004 食品添加剂羧甲基纤维素钠 Foodadditive- Sodium carboxymethyl cellulose 2007-12-01发布2008-01-01实施 山东一滕化工有限公司发布
Q/09FYT002-2007 前言 本标准由山东一滕化工有限公司首次提出。 本标准于2007年12月01日发布，2008年01月01日实施。 本标准自发布之日起有效期三年，到期复审。 本标准由山东一滕化工公司技术质检部负责起草。 本标准主要起草人：李坤赵焕玲
Q/09FYT002-2004 1范围 本标准规定了食品添加剂後甲基纤维素俐的产品分类和命名，要求，试验方法，检验规则以及标志、包装、运输和贮存。 本标准适用于以纤维素、氢氧化钠及氯乙酸或其钠盐为主要原料制得的食品添加剂羧甲基纤维素。 2、规范性引用文件 下列文件中的条款通过本标准的引用而成为本标准的条款。凡是注日期的引用文件，其随后所有 的修改单〈不包括勘误的内容〉或修订版均不适用于本标准，然而，鼓励根据本标准达成协议的各方研究是否可使用这些文件的最新版本。凡是不注日期的引用文件，其最新版本适用于本标准。 GB/TT191包装储运图示标志(GB/T191-2000，eqv ISO780;1997 GB/T601化学试剂标准滴定溶液的制备 GB/T 602化学试剂杂质测定用标准溶液的制备 (GB/T 602-2002 , ISO 6353-1: 1982 ,NEQ) GB/T 603化学试剂试验方法中所用制剂及制品的制备 (GB/T 503-2002 , lS0 5353-1: 1982 , NEQ) GB/T 5009. 75食品添加剂中铅的测定 GB/T5009.76食品添加剂中砷的测定 GB/T6678-2003化工产品采样总则 GB/T6682分析实验室用水规格和试验方法(GB/T6682-1992，neqISO3696:1987 GB/T 6582分析实验室用水规格和试验方法 CGB/T 6682一 1992， neq 150 3595:1987) GB/T 9724化学试剂 pH测定通则 GB/T9725电位滴定法通则电位滴定法通则 3、类型和命名 3.1产品分型 食品添加剂羧甲基纤维素钠按粘度范围分为四类。其型号、命名及对应粘度范围见表1 表1 食品添加剂羧甲基纤维素钠型号
1.1羧甲基纤维素（CMC） 1.1.1 羧甲基纤维素简介 羧甲基纤维素(简称CMC)是最重要的纤维素醚之一，它是以天然纤维素(浆粕)为基本原料，经过碱化、醚化反应而生成的，是天然纤维素经化学改性得到的一种具有醚结构的衍生物。 分子链上的羧基可以生成盐，即羧甲基纤维素钠（Na-CMC），习惯上将其称为CMC(Carboxymethyl Cellulose)，是一种阴离子型醚。 羧甲基纤维素钠一般为粉末状的固体，有时也呈现颗粒状或纤维状，颜色为白色或淡黄色，没有特殊的气味，是一种大分子化学物质，CMC具有很强的引湿性，能溶于水中，在水中形成透明度较高的粘稠溶液[1]。CMC不溶于一般的有机溶液，例如乙醇、乙醚、氯仿及苯等，但是可以溶于水，CMC直接溶于水中速度较为缓慢，但溶解度还是很大的，并且CMC的水溶液具有一定的粘度[2]。固体CMC在一般环境下较稳定，因为具有一定的吸水性和引湿性，在干燥的环境下，可以长期保存[2-3]。 由于CMC具有宝贵的胶体化学性质，所以近年来它被作为乳化剂、上浆剂、粘结剂、稳定剂等而被广泛应用于纺织、石油、合成洗涤剂、牙膏、医药、建筑、陶瓷等工业中。实践证明，CMC不仅可代替淀粉等物质，节约工业用粮，而且有许多独到之处。因此，它在国民经济中有一定的地位，得到了世界各国的普遍重视[4]。 1.1.2 羧甲基纤维素的制备 目前，羧甲基纤维素的生产方法可分为两大类，即水媒法和溶媒法。在反应过程中，加入水作为反应介质的方法叫水媒法，用于生产碱性低质的羧甲基纤维素产品；溶媒法则是以有机溶剂为介质的方法，由于有机溶剂在反应过程中传热迅速、传质均匀，可有效减少碱纤维素的水解逆反应，因此溶媒法副反应少，醚化剂利用率高，所得到的产品纯度高，粘度高，主要用于生产中高品质的羧甲基纤维素产品。国内生产羧甲基纤维素多采用溶媒法。 CMC的技术指标主要有聚合度、取代度、纯度、含水量及其水溶液的黏度、pH等。其中取代度是最关键的指标，决定了CMC的性质和用途。取代度（DS）