CN110563860A - preparation method of carboxymethyl chitosan - Google Patents
preparation method of carboxymethyl chitosan Download PDFInfo
- Publication number
- CN110563860A CN110563860A CN201911020069.XA CN201911020069A CN110563860A CN 110563860 A CN110563860 A CN 110563860A CN 201911020069 A CN201911020069 A CN 201911020069A CN 110563860 A CN110563860 A CN 110563860A
- Authority
- CN
- China
- Prior art keywords
- carboxymethyl chitosan
- solution
- reaction
- ethanol
- sodium hydroxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
the invention relates to a preparation method of carboxymethyl chitosan, which comprises the steps of adding chitin into a sodium hydroxide dimethyl sulfoxide solution for deacetylation reaction, directly adding a chloroacetic acid ethanol solution into a reaction solution for carboxymethylation reaction after the reaction is finished, and washing and drying after the reaction is finished to obtain the carboxymethyl chitosan. The method provided by the invention has the advantages of short reaction time, large molecular weight and high viscosity of the prepared carboxymethyl chitosan, simple preparation process, recyclable solvent and no pollution to the environment.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to a preparation method of carboxymethyl chitosan.
background
Carboxymethyl chitosan is a medical macromolecular polysaccharide substance with good biocompatibility, biodegradability and biological activity, and has the effects of easing pain, stopping bleeding, inhibiting bacteria and promoting wound healing clinically.
the traditional carboxymethyl chitosan production process comprises chitosan preparation by chitosan deacetylation, carboxymethyl preparation of carboxymethyl chitosan after washing and drying a chitosan crude product, and has complex preparation process and long reaction time. Patent application document with publication number CN 104292365 discloses a method for combining chitosan and carboxymethyl chitosan preparation processes into one, which provides a method for directly adding chloroacetic acid to react after chitosan deacetylation is completed, and separating out carboxymethyl chitosan under low temperature condition. Because the components of the reaction solution are complex, reaction byproducts can be separated out along with the carboxymethyl chitosan under the low-temperature condition, the removal is difficult, and the purity of the obtained product is low.
Disclosure of Invention
the technical problem to be solved by the invention is to provide a novel preparation method of carboxymethyl chitosan, the provided preparation method can obviously shorten the reaction time, the prepared carboxymethyl chitosan has high purity and large molecular weight, and the used solvent can be recycled without polluting the environment.
to solve the technical problems, the technical scheme provided by the invention is as follows:
A preparation method of carboxymethyl chitosan is characterized in that: the method comprises the following steps:
(1) Preparing an alkaline solution: weighing a certain amount of sodium hydroxide, adding the sodium hydroxide into dimethyl sulfoxide, stirring for dissolving, and heating to 120-150 ℃;
(2) deacetylation and carboxymethylation reaction: adding chitin into the alkaline solution in the step (1), and stirring and reacting for 10-40 min; after the reaction is finished, cooling to 50-80 ℃, and dropwise adding chloroacetic acid ethanol solution to perform carboxymethylation reaction;
(3) And (3) post-treatment: filtering, adding 65-100% ethanol solution, adjusting pH to neutral with acid solution, filtering, washing with ethanol, drying, packaging, and sterilizing.
Further, the preparation method of carboxymethyl chitosan of the present invention comprises: the concentration of the sodium hydroxide in the alkaline solution in the step (1) is 0.05 g/ml-0.2 g/ml.
Further, the preparation method of carboxymethyl chitosan of the present invention comprises: the concentration of the sodium hydroxide in the alkaline solution in the step (1) is 0.08-0.12 g/ml.
Further, the preparation method of carboxymethyl chitosan of the present invention comprises: the mass ratio g/g of the chitin to the sodium hydroxide in the alkaline solution in the step (2) is 1: 1-3.
Further, the preparation method of carboxymethyl chitosan of the present invention comprises: in the step (2), the mass concentration of the chloroacetic acid is 40g/100 ml-60 g/100ml, the mass ratio g/g of the chitin to the chloroacetic acid is 1: 0.5-0.8, and the reaction time is 1 h-3 h.
further, the preparation method of carboxymethyl chitosan of the present invention comprises: the acidic solution in the step (3) is a hydrochloric acid solution, an acetic acid solution or a sulfuric acid solution.
Further, the preparation method of carboxymethyl chitosan of the present invention comprises: in the step (3), the ethanol is washed by 70% ethanol for 3-8 times, and the ethanol is washed by 95% ethanol for 1-4 times.
Further, the preparation method of carboxymethyl chitosan of the present invention comprises: the drying in the step (3) is vacuum drying, and the drying temperature is 50-65 ℃.
the carboxymethyl chitosan is sterilized by irradiation.
The following is a description of the process and principles of the present invention:
adding chitin into a sodium hydroxide dimethyl sulfoxide solution for deacetylation reaction, directly adding a chloroacetic acid ethanol solution into a reaction solution for carboxymethylation reaction after the reaction is finished, and washing and drying after the reaction is finished to obtain the carboxymethyl chitosan.
The applicant finds that the alkalinity of the sodium hydroxide in the dimethyl sulfoxide solution is much stronger than that in the water solution, the chitosan is subjected to deacetylation reaction in the sodium hydroxide dimethyl sulfoxide solution with strong alkalinity, the reaction can be completed within 10-40 min, and the using amount of the sodium hydroxide is obviously reduced. Because the reaction time is short, the damage to the molecular structure of the chitosan is small, the molecular weight of the obtained product is large, and the viscosity of the product is correspondingly large.
The chitosan and the carboxymethyl chitosan are not dissolved in the dimethyl sulfoxide solution, the carboxymethyl chitosan prepared by carboxymethyl reaction of the chitosan is still solid, the by-product generated by the reaction can be removed by the procedures of filtering, washing and the like, and the product purity is high.
The invention has the following beneficial effects:
(1) The chitosan deacetylation reaction time is short, and the obtained product has large molecular weight and high viscosity.
(2) the dimethyl sulfoxide used as a solvent for reaction and the ethanol used for washing can be recycled by rectification or distillation, no waste water is generated, and no pollution is caused to the environment.
(3) The technical scheme provided by the invention is simple, easy to operate and suitable for industrial scale-up production.
Detailed Description
The technical solution of the present invention is illustrated by the following specific examples, but the examples are not to be construed as limiting the scope of the present invention.
Example 1:
(1) Preparing an alkaline solution: weighing 90g of sodium hydroxide, adding the sodium hydroxide into 900mL of dimethyl sulfoxide, stirring for dissolving, and heating to 135 ℃;
(2) Deacetylation and carboxymethylation reaction: weighing 50g of chitin, adding into the alkaline solution, and stirring for reaction for 25 min; after the reaction is finished, cooling to 55 ℃, adding 65ml of chloroacetic acid ethanol solution with the concentration of 40% for 6 times in total, and carrying out carboxymethylation reaction for 3 hours;
(3) And (3) post-treatment: filtering to obtain carboxymethyl chitosan crude product, adding 5 times volume of 70% ethanol solution of the crude product, adjusting pH of reaction solution to 7.2 with 50% acetic acid solution, filtering, sequentially washing with 70% ethanol for 7 times, washing with 95% ethanol for 3 times, vacuum drying at 60 deg.C for 6h, packaging, and sterilizing.
Example 2:
(1) preparing an alkaline solution: weighing 180g of sodium hydroxide, adding the sodium hydroxide into 900mL of dimethyl sulfoxide, stirring for dissolving, and heating to 120 ℃;
(2) Deacetylation and carboxymethylation reaction: weighing 60g of chitin, adding into the alkaline solution, and stirring for reaction for 10 min; after the reaction is finished, cooling to 65 ℃, adding 90ml of chloroacetic acid ethanol solution with the concentration of 50% for 6 times in total, and carrying out carboxymethylation reaction for 1 h;
(3) And (3) post-treatment: filtering to obtain carboxymethyl chitosan crude product, adding 5 times volume of 95% ethanol solution of the crude product, adjusting pH of reaction solution to 7.1 with 50% hydrochloric acid solution, filtering, sequentially washing with 70% ethanol for 6 times, washing with 95% ethanol for 2 times, vacuum drying at 65 deg.C for 6h, packaging, and sterilizing.
Example 3:
(1) preparing an alkaline solution: weighing 45g of sodium hydroxide, adding the sodium hydroxide into 900mL of dimethyl sulfoxide, stirring for dissolving, and heating to 150 ℃;
(2) deacetylation and carboxymethylation reaction: weighing 40g of chitin, adding into the alkaline solution, and stirring for reacting for 40 min; after the reaction is finished, cooling to 80 ℃, adding 40ml of chloroacetic acid ethanol solution with the concentration of 60% for 6 times in total, and carrying out carboxymethylation reaction for 2 hours;
(3) And (3) post-treatment: filtering to obtain carboxymethyl chitosan crude product, adding 5 times volume of 95% ethanol solution of the crude product, adjusting pH of reaction solution to 7.2 with 50% acetic acid solution, filtering, sequentially washing with 70% ethanol for 8 times, washing with 95% ethanol for 2 times, vacuum drying at 55 deg.C for 8 hr, packaging, and sterilizing.
comparative example:
Preparing carboxymethyl chitosan by adopting a conventional two-step method:
(1) Preparing an alkaline solution: weighing 450g of sodium hydroxide, adding the sodium hydroxide into 900mL of purified water, stirring for dissolving, and heating to 120 ℃;
(2) Deacetylation reaction: weighing 55g of chitin, adding into the alkaline solution, and stirring for reacting for 60 min; after the reaction is finished, filtering, washing the reaction product to be neutral by purified water, and drying the reaction product;
(3) carboxymethylation reaction: taking 40g of the dried chitosan, adding 400ml of isopropanol, slowly adding 80ml of 50% sodium hydroxide solution under the stirring condition, continuously stirring for 2 hours, adding 88ml of 55% chloroacetic acid ethanol solution for 6 times in total, and carrying out carboxymethylation reaction at the reaction temperature of 65 ℃ for 3 hours;
(4) and (3) post-treatment: filtering to obtain carboxymethyl chitosan crude product, adding 5 times volume of 70% ethanol solution of the crude product, adjusting pH of reaction solution to 7.2 with 50% acetic acid solution, filtering, sequentially washing with 70% ethanol for 7 times, washing with 95% ethanol for 2 times, vacuum drying at 55 deg.C for 8 hr, packaging, and sterilizing.
the carboxymethyl chitosan samples prepared in examples 1 to 3 and comparative examples are detected, and the detection results of the key indexes are as follows:
。
The test result shows that the technical scheme provided by the invention has short reaction time, and the prepared carboxymethyl chitosan has high molecular weight and viscosity, has better anti-adhesion and lubrication effects, can be used as a lubricant in bone joints and can prevent and treat traumatic or degenerative osteoarthritis.
The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (8)
1. A preparation method of carboxymethyl chitosan is characterized in that: the method comprises the following steps:
(1) preparing an alkaline solution: weighing a certain amount of sodium hydroxide, adding the sodium hydroxide into dimethyl sulfoxide, stirring for dissolving, and heating to 120-150 ℃;
(2) Deacetylation and carboxymethylation reaction: adding chitin into the alkaline solution in the step (1), and stirring and reacting for 10-40 min; after the reaction is finished, cooling to 50-80 ℃, and dropwise adding chloroacetic acid ethanol solution to perform carboxymethylation reaction;
(3) and (3) post-treatment: filtering, adding 65-100% ethanol solution, regulating pH to neutral with acid solution, filtering, washing with ethanol, drying, packaging, and sterilizing.
2. The method for preparing carboxymethyl chitosan according to claim 1, wherein: the concentration of the sodium hydroxide in the alkaline solution in the step (1) is 0.05 g/ml-0.2 g/ml.
3. The method for preparing carboxymethyl chitosan according to claim 2, wherein: the concentration of the sodium hydroxide in the alkaline solution in the step (1) is 0.08-0.12 g/ml.
4. The method for preparing carboxymethyl chitosan according to claim 1, wherein: the mass ratio g/g of the chitin to the sodium hydroxide in the alkaline solution in the step (2) is 1: 1-3.
5. The method for preparing carboxymethyl chitosan according to claim 1, wherein: in the step (2), the mass concentration of the chloroacetic acid is 40g/100 ml-60 g/100ml, the mass ratio g/g of the chitin to the chloroacetic acid is 1: 0.5-0.8, and the reaction time is 1 h-3 h.
6. the method for preparing carboxymethyl chitosan according to claim 1, wherein: the acidic solution in the step (3) is a hydrochloric acid solution, an acetic acid solution or a sulfuric acid solution.
7. the method for preparing carboxymethyl chitosan according to claim 1, wherein: in the step (3), the ethanol is washed by 70% ethanol for 3-8 times, and the ethanol is washed by 95% ethanol for 1-4 times.
8. The method for preparing carboxymethyl chitosan according to claim 1, wherein: the drying in the step (3) is vacuum drying, and the drying temperature is 50-65 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911020069.XA CN110563860A (en) | 2019-10-25 | 2019-10-25 | preparation method of carboxymethyl chitosan |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911020069.XA CN110563860A (en) | 2019-10-25 | 2019-10-25 | preparation method of carboxymethyl chitosan |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110563860A true CN110563860A (en) | 2019-12-13 |
Family
ID=68785814
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911020069.XA Pending CN110563860A (en) | 2019-10-25 | 2019-10-25 | preparation method of carboxymethyl chitosan |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110563860A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113332236A (en) * | 2020-03-03 | 2021-09-03 | 杭州协合医疗用品有限公司 | Preparation method of carboxymethyl chitosan anti-adhesion flushing fluid for surgical operation |
| CN113583148A (en) * | 2021-08-05 | 2021-11-02 | 青岛海洋科学与技术国家实验室发展中心 | Preparation method of low-immunogenicity chitin and obtained chitin |
| CN114388776A (en) * | 2021-12-06 | 2022-04-22 | 宜宾光原锂电材料有限公司 | Method for removing impurity sodium by washing nickel-cobalt-manganese ternary precursor |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4424346A (en) * | 1981-06-04 | 1984-01-03 | Canadian Patents And Development Ltd. | Derivatives of chitins, chitosans and other polysaccharides |
| CN1629196A (en) * | 2004-10-20 | 2005-06-22 | 中国海洋大学 | A kind of method and application thereof for preparing carboxymethyl chitosan |
| CN104788584A (en) * | 2014-01-17 | 2015-07-22 | 厦门大学 | New technology for clean production of chitosan and carboxymethyl chitosan by using crustacean shell raw materials |
| CN106046200A (en) * | 2016-08-19 | 2016-10-26 | 沧州师范学院 | Preparation method of carboxymethyl chitosan |
| CN108017723A (en) * | 2016-11-03 | 2018-05-11 | 常州药物研究所有限公司 | The preparation method of high quality high molecular weight carboxymethyl chitosan |
-
2019
- 2019-10-25 CN CN201911020069.XA patent/CN110563860A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4424346A (en) * | 1981-06-04 | 1984-01-03 | Canadian Patents And Development Ltd. | Derivatives of chitins, chitosans and other polysaccharides |
| CN1629196A (en) * | 2004-10-20 | 2005-06-22 | 中国海洋大学 | A kind of method and application thereof for preparing carboxymethyl chitosan |
| CN104788584A (en) * | 2014-01-17 | 2015-07-22 | 厦门大学 | New technology for clean production of chitosan and carboxymethyl chitosan by using crustacean shell raw materials |
| CN106046200A (en) * | 2016-08-19 | 2016-10-26 | 沧州师范学院 | Preparation method of carboxymethyl chitosan |
| CN108017723A (en) * | 2016-11-03 | 2018-05-11 | 常州药物研究所有限公司 | The preparation method of high quality high molecular weight carboxymethyl chitosan |
Non-Patent Citations (8)
| Title |
|---|
| XUEQIONG YIN等: "Preparation and antibacterial activity of Schiff bases from O-carboxymethyl chitosan and para-substituted benzaldehydes", 《POLYMER BULLETIN》 * |
| 丁纯梅等: "完全脱乙酰度壳聚糖的制备及表征", 《华东理工大学学报(自然科学版)》 * |
| 冯树波等: "羧甲基壳聚糖制备中的溶剂影响及精制方法研究", 《化学研究与应用》 * |
| 刘树恒主编: "《化学实验绿色化的探索与实践》", 31 August 2012 * |
| 吴友吉等: "高取代度羧甲基壳聚糖的制备", 《合成化学》 * |
| 汪多仁主编: "《有机食品营养强化剂》", 31 August 2008 * |
| 荣国斌主编: "《大学有机化学基础 下册》", 31 August 2006, 华东理工大学出版社 * |
| 郑丝柳等: "利用废弃淡水龙虾壳制备羧甲基壳聚糖", 《化工技术与开发》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113332236A (en) * | 2020-03-03 | 2021-09-03 | 杭州协合医疗用品有限公司 | Preparation method of carboxymethyl chitosan anti-adhesion flushing fluid for surgical operation |
| CN113583148A (en) * | 2021-08-05 | 2021-11-02 | 青岛海洋科学与技术国家实验室发展中心 | Preparation method of low-immunogenicity chitin and obtained chitin |
| CN114388776A (en) * | 2021-12-06 | 2022-04-22 | 宜宾光原锂电材料有限公司 | Method for removing impurity sodium by washing nickel-cobalt-manganese ternary precursor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107383236B (en) | A novel water-soluble natural polysaccharide antibacterial material and preparation method thereof | |
| CA2313836C (en) | Chitosan and method of preparing chitosan | |
| CN110563860A (en) | preparation method of carboxymethyl chitosan | |
| CN101550199B (en) | Method for preparing sodium hyaluronate from hyaluronic acid zymotic fluid | |
| CN102276756A (en) | Preparation method of chitosan hydroxybutyl derivative | |
| Muslim et al. | Chitosan and carboxymethyl chitosan from fish scales of Labeo rohita | |
| CN103539868B (en) | A kind of method of preparing CMC | |
| Zhang et al. | Facile production of chitin from shrimp shells using a deep eutectic solvent and acetic acid | |
| CN101508741B (en) | Process for synthesis of methylation-beta-cyclodextrin with dimethyl carbonate and beta-cyclodextrin | |
| CN107915848A (en) | A kind of preparation method of chitin whisker/hydroxyl butyl chitosan temperature-sensitive hydrogel | |
| CN103554303B (en) | A kind of method of purifying cm-chitosan | |
| KR20070004159A (en) | Method for producing hyaluronic acid crosslinked product | |
| CN1944467A (en) | Chitosan guanidine salt derivative and its preparing method | |
| CN104059166A (en) | Method for preparing oligomeric hyaluronic acid by hyaluronic acid broth | |
| JP6486554B2 (en) | Method for producing heparinoid | |
| CN107915850B (en) | Selenium-containing chitosan hydrogel and preparation method, degradation method and application thereof | |
| WO2011114470A1 (en) | Hyaluronic acid purification method and production method | |
| CN105622778A (en) | Preparation method of water-soluble chitosan | |
| CN108456262A (en) | A kind of preparation process of high purity heparin sodium | |
| CN1217957C (en) | Method for preparing high-qualtiy chitosan | |
| KR20000036774A (en) | Preparing Methode for Aqueous Chitosan | |
| CN114702607B (en) | Water-soluble hydroxymethyl propyl chitosan and preparation method thereof | |
| CN113072651A (en) | Preparation method of oligomeric sodium hyaluronate solution | |
| US7345165B2 (en) | Method for preparing water-soluble free amine chitosan | |
| CN101503480B (en) | Microwave synthesizing method for disproportionated rosin-chitosan conjugate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20191213 |