Preparation method and application of oxidized sodium alginate
By using sodium periodate oxidation, ethylene glycol condensation, and phosphoric acid hydrolysis, combined with hydrophilic modified filter membrane filtration, the problem of unstable oxidation degree of oxidized sodium alginate was solved, and stable oxidized sodium alginate was prepared for drug-loaded microspheres and tissue engineering applications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- QINGDAO BRIGHT MOON SEAWEED GROUP
- Filing Date
- 2025-02-14
- Publication Date
- 2026-07-07
AI Technical Summary
In existing technologies, the oxidation degree of sodium alginate is unstable, and the aldehyde group is easily affected by the environment and reagents during the purification process, resulting in the final product performance not meeting expectations.
Sodium alginate solution was oxidized with sodium periodate, and the reaction was terminated with ethylene glycol to generate a stable acetal group. Hydrolysis was then carried out by adjusting the pH with phosphoric acid. The solution was filtered multiple times using a hydrophilic modified polytetrafluoroethylene filter membrane to remove impurities and prepare stable oxidized sodium alginate.
Stable control of the oxidation degree of sodium alginate was achieved, and the aldehyde group was less affected during the purification process. The prepared sodium alginate can be used for drug-loaded microspheres, tissue engineering scaffolds and in vivo wound dressings, and the degradation rate can be controlled.
Smart Images
Figure BDA0005272608550000061 
Figure BDA0005272608550000071
Abstract
Description
Technical Field
[0001] This application relates to the field of bioengineering technology, and more specifically, to a method for preparing and using oxidized sodium alginate. Background Technology
[0002] Sodium alginate is a polysaccharide extracted from brown algae. It exhibits gelling properties. Adding divalent cations such as Ca2+ to a sodium alginate solution... 2+ Ba 2+ 、Sr 2+ These cations interact electrostatically with the carboxyl groups on the guluronic acid of alginate to form a milky white gel. Sodium alginate also has high biocompatibility and is free of in vivo degradation enzymes.
[0003] Due to its biocompatibility, low toxicity, and relatively low price, alginate is widely used in drug delivery systems and tissue engineering. However, alginate lacks degrading enzymes in the human body, and its degradation rate is very low. Compared to pristine alginate hydrogels, oxidized alginate hydrogels show a significant decrease in strength over time. In practical applications, it is necessary to select an appropriate degree of oxidation that balances degradation time and gel performance.
[0004] After sodium alginate is oxidized to obtain sodium alginate, it needs to be purified. Since the aldehyde group is relatively reactive, it may be affected by the purification operation or the environment during the purification process, causing the aldehyde group to react and affecting the final oxidation degree of sodium alginate. Because the influence of the aldehyde group is uncontrollable, it is not easy to predict the final product performance of sodium alginate, resulting in unstable oxidation degree of the obtained sodium alginate, which does not meet the initial expectations. Summary of the Invention
[0005] To make the oxidation degree of oxidized sodium alginate more stable, this application provides a method for preparing oxidized sodium alginate and its application.
[0006] In a first aspect, this application provides a method for preparing oxidized sodium alginate, employing the following technical solution:
[0007] A method for preparing oxidized sodium alginate includes the following steps:
[0008] Oxidation: Add sodium alginate to water to prepare sodium alginate solution, add sodium periodate solution to sodium alginate solution and mix well, react at 50-70℃ for 2-2.2h, and then add excess ethylene glycol to terminate the oxidation reaction.
[0009] Precipitation: Add excess acetone to the solution after the reaction, centrifuge to dehydrate, precipitate, separate, and dry to obtain powder A; Condensation: After powder A is mixed with ethylene glycol and thoroughly mixed, dry HCl gas is introduced, and the mixture is kept at 14-16℃ for 6-7 hours. Then, it is extracted with chloroform. After the extract is dried, the chloroform is distilled off to obtain powder B.
[0010] Filtration: Dissolve powder B in acetone and stir magnetically to form a homogeneous solution. Filter the homogeneous solution multiple times using a filter membrane to obtain filtrate. After static precipitation, separation, and drying, obtain powder C.
[0011] Hydrolysis: After dissolving powder C in water, phosphoric acid is added to adjust the pH. After reacting for 1-1.2 hours, excess acetone is added, and the mixture is allowed to stand to precipitate, separated, and dried. The process of adding acetone, precipitating, separating, and drying is repeated multiple times to finally obtain sodium alginate oxidized powder.
[0012] By adopting the above technical solution, sodium alginate undergoes oxidation by breaking the carbon-carbon bond in the cis-diol structure under the action of sodium periodate, forming two aldehyde groups. This process yields oxidized sodium alginate. Excess ethylene glycol is used to terminate the oxidation reaction, controlling the degree of oxidation of oxidized sodium alginate within the required range. Acetone is then used for crude extraction, causing oxidized sodium alginate and impurities such as proteins to precipitate out.
[0013] The aldehyde group of oxidized sodium alginate reacts with ethylene glycol to form acetal. Acetal is chemically stable and does not easily denature or react during repeated precipitation, centrifugation and filtration. Through multiple filtrations, the content of impurities in the filtrate can be effectively reduced.
[0014] After adjusting the pH with phosphoric acid, the hydrolysis reaction of the acetal was promoted, the protection of the aldehyde group was removed, and acetone was used for precipitation. The ethylene glycol produced by the hydrolysis reaction and the phosphoric acid, which acted as a catalyst, dissolved in acetone, while sodium oxidized alginate, which has low solubility in acetone, precipitated out. This process yielded sodium oxidized alginate with high purity. At the same time, the aldehyde group in the sodium oxidized alginate was protected during the purification process, making the oxidation degree of the finished sodium oxidized alginate relatively stable and able to meet the requirements of a specific oxidation degree.
[0015] Preferably, the sodium alginate solution has a sodium alginate concentration of 8-10 wt% and a sodium alginate to sodium periodate molar ratio of 1:0.03-0.04.
[0016] By adopting the above technical solution and controlling the molar ratio between sodium alginate and sodium periodate, the degree of oxidation of sodium alginate by sodium periodate can be effectively controlled, thereby controlling the degree of oxidation of sodium alginate.
[0017] Preferably, the molar ratio of powder A to ethylene glycol is 1:0.01-0.02.
[0018] By adopting the above technical solution and controlling the molar ratio between powder A and ethylene glycol, the aldehyde groups in the oxidized sodium alginate in powder A undergo a condensation reaction with ethylene glycol, thereby ensuring that the aldehyde groups are fully protected.
[0019] Preferably, in the hydrolysis step, phosphoric acid is added to adjust the pH to 3.5-4.
[0020] By adopting the above technical solution and adjusting the pH of the solution, the acetal can be hydrolyzed in an acidic environment to generate aldehydes and alcohols, thereby removing the protection of sodium alginate oxide by ethylene glycol. Too high a pH will easily reduce the hydrolysis rate of the acetal, while too low a pH will easily cause sodium alginate oxide to precipitate.
[0021] Preferably, the filter membrane is a hydrophilic modified polytetrafluoroethylene filter membrane.
[0022] By adopting the above technical solution, the polytetrafluoroethylene filter membrane has good resistance to organic solvents and can be used for acetone filtration. The hydrophilically modified polytetrafluoroethylene filter membrane has good hydrophilicity and antifouling properties. The microporous structure of the filter membrane can effectively filter out impurities with large molecular weights, such as impurities and proteins contained in powder B. The molecular weight of sodium alginate oxidized after oxidation is reduced and passes through the polytetrafluoroethylene filter membrane along with the acetone.
[0023] Preferably, the method for preparing the hydrophilic modified polytetrafluoroethylene filter membrane includes the following steps: mixing polytetrafluoroethylene filter membrane, sodium p-styrene sulfonate, sodium bisulfite and water, purging with nitrogen and heating to 55-60°C, slowly and continuously adding acrylic acid and ammonium persulfate, reacting for 5-5.5 hours, removing the polytetrafluoroethylene filter membrane, washing and drying to obtain the hydrophilic modified polytetrafluoroethylene filter membrane.
[0024] By adopting the above technical solution, sulfonic acid groups are introduced into the surface of polytetrafluoroethylene (PTFE) filter membrane by copolymerizing sodium styrene sulfonate and acrylic acid, which gives the PTFE filter membrane good hydrophilicity. Most of the impurities in sodium alginate are hydrophilic proteins. After modification with PTFE, the adsorption effect on hydrophilic proteins is increased. At the same time, a large amount of hydrophilic copolymer is deposited on the surface of the modified PTFE filter membrane, making it difficult for the PTFE filter membrane to adsorb proteins. The hydrophilic modified PTFE filter membrane has good antifouling performance during use.
[0025] Preferably, the mass ratio of sodium p-styrene sulfonate to acrylic acid is 6:(6.8-7.1), and the concentration of sodium p-styrene sulfonate is 11-12 wt%.
[0026] By adopting the above technical solution, and by controlling the mass ratio and concentration of sodium styrene sulfonate and acrylic acid, the deposition amount of hydrophilic copolymer on the surface of polytetrafluoroethylene filter membrane can be regulated, thereby improving hydrophilicity and giving the polytetrafluoroethylene filter membrane good antifouling performance.
[0027] Secondly, this application provides an application of oxidized sodium alginate, employing the following technical solution:
[0028] An application of oxidized sodium alginate, used alone or in combination with sodium alginate, for drug-loaded microspheres, tissue engineering scaffolds, and in vivo wound dressings.
[0029] By adopting the above technical solution, the oxidation degree of sodium alginate prepared by the method of this application is relatively stable. The aldehyde group in sodium alginate is less affected by the environment and reagents during the purification process. The oxidation degree of the prepared sodium alginate meets the initial expectation and can relatively stably control the oxidation degree of sodium alginate, thereby controlling the degradation rate of drug-loaded microspheres, tissue engineering scaffolds and in vivo wound dressings in the human body.
[0030] In summary, this application has the following beneficial effects:
[0031] 1. Since this application uses ethylene glycol to react with the aldehyde group in sodium alginate oxide to generate acetal, the acetal is relatively stable. When performing purification operations such as precipitation, centrifugation and filtration on sodium alginate oxide, the acetal is not easily affected by the environment and reagents, effectively protecting the aldehyde group in sodium alginate oxide.
[0032] 2. In this application, phosphoric acid is preferably used to adjust the pH and catalyze the hydrolysis reaction of acetal to restore the aldehyde group of sodium alginate. Phosphoric acid and the generated ethylene glycol are soluble in acetone. Sodium alginate has low solubility in acetone and precipitates out. After static precipitation, sodium alginate powder is obtained.
[0033] 3. The oxidized sodium alginate in this application can be used in drug-loaded microspheres, tissue engineering scaffolds, and in vivo wound dressings. The oxidized sodium alginate prepared by the method of this application has a relatively stable degree of oxidation. The oxidized sodium alginate, used alone or in combination with sodium alginate, can effectively control the degradation rate of drug-loaded microspheres, tissue engineering scaffolds, and in vivo wound dressings in the human body. Detailed Implementation
[0034] The present application will be further described in detail below with reference to the embodiments.
[0035] Preparation Examples of Hydrophilic Modified Polytetrafluoroethylene Filter Membranes 1-4
[0036] Preparation Example 1
[0037] 5g of polytetrafluoroethylene (PTFE) filter membrane, sodium p-styrene sulfonate, sodium bisulfite, and water were mixed, and then heated to 60°C after purging with nitrogen. Acrylic acid and ammonium persulfate were slowly and continuously added dropwise. After reacting for 5 hours, the PTFE filter membrane was removed, washed, and dried to obtain a hydrophilic modified PTFE filter membrane. The concentration of sodium p-styrene sulfonate was 11wt%, the mass ratio of sodium p-styrene sulfonate to acrylic acid was 6:7.1, the concentration of ammonium persulfate was 1.5wt%, and the concentration of sodium bisulfite was 1wt%.
[0038] Preparation Example 2
[0039] 5g of polytetrafluoroethylene (PTFE) filter membrane, sodium p-styrene sulfonate, sodium bisulfite, and water were mixed, and then heated to 55°C after purging with nitrogen. Acrylic acid and ammonium persulfate were slowly and continuously added dropwise. After reacting for 5.5 hours, the PTFE filter membrane was removed, washed, and dried to obtain a hydrophilic modified PTFE filter membrane. The concentration of sodium p-styrene sulfonate was 12wt%, the mass ratio of sodium p-styrene sulfonate to acrylic acid was 6:6.8, the concentration of ammonium persulfate was 1.7wt%, and the concentration of sodium bisulfite was 1.2wt%.
[0040] Preparation Example 3
[0041] The difference between Preparation Example 3 and Preparation Example 1 is that the mass ratio of sodium p-styrene sulfonate to acrylic acid in Preparation Example 3 is 6:5.
[0042] Preparation Example 4
[0043] The difference between Preparation Example 4 and Preparation Example 1 is that the mass ratio of sodium p-styrene sulfonate to acrylic acid in Preparation Example 4 is 6:8.
[0044] Example
[0045] Example 1
[0046] A method for preparing oxidized sodium alginate includes the following steps:
[0047] Oxidation: Sodium alginate was added to water to prepare an 8wt% sodium alginate solution. Sodium periodate solution was added to the sodium alginate solution and mixed evenly. The molar ratio of sodium alginate to sodium periodate was 1:0.03. After reacting at 70℃ for 2 hours, excess ethylene glycol was added to terminate the oxidation reaction.
[0048] Precipitation: Add excess acetone to the solution after the reaction, centrifuge to dehydrate, precipitate, separate, and dry to obtain powder A;
[0049] Condensation: Powder A with a molar ratio of 1:0.01 is mixed with ethylene glycol and then dry HCl gas is introduced. After being kept at 14°C for 7 hours, it is extracted with chloroform. After the extract is dried, the chloroform is distilled off to obtain powder B.
[0050] Filtration: Powder B was dissolved in acetone and magnetically stirred to form a homogeneous solution. The homogeneous solution was filtered four times using a filter membrane to obtain filtrate. After static precipitation, separation, and drying, powder C was obtained. In this embodiment, the filter membrane used was the hydrophilic modified polytetrafluoroethylene filter membrane prepared in Preparation Example 1.
[0051] Hydrolysis: After dissolving powder C in water, phosphoric acid was added to adjust the pH of the solution to 3.5. After reacting for 1 hour, excess acetone was added, and the mixture was allowed to stand to precipitate, separated, and dried. The process of adding acetone, precipitating, separating, and drying was repeated multiple times to finally obtain sodium alginate oxidized powder.
[0052] Example 2
[0053] A method for preparing oxidized sodium alginate includes the following steps:
[0054] Oxidation: Sodium alginate was added to water to prepare a 10wt% sodium alginate solution. Sodium periodate solution was added to the sodium alginate solution and mixed evenly. The molar ratio of sodium alginate to sodium periodate was 1:0.04. After reacting at 50℃ for 2.2h, excess ethylene glycol was added to terminate the oxidation reaction.
[0055] Precipitation: Add excess acetone to the solution after the reaction, centrifuge to dehydrate, precipitate, separate, and dry to obtain powder A;
[0056] Condensation: Powder A with a molar ratio of 1:0.02 is mixed with ethylene glycol and then dry HCl gas is introduced. After being kept at 16°C for 6 hours, it is extracted with chloroform. After the extract is dried, the chloroform is distilled off to obtain powder B.
[0057] Filtration: Powder B was dissolved in acetone and magnetically stirred to form a homogeneous solution. The homogeneous solution was filtered four times using a filter membrane to obtain filtrate. After static precipitation, separation, and drying, powder C was obtained. In this embodiment, the filter membrane used was the hydrophilic modified polytetrafluoroethylene filter membrane prepared in Preparation Example 2.
[0058] Hydrolysis: After dissolving powder C in water, phosphoric acid was added to adjust the pH of the solution to 4. After reacting for 1.2 hours, excess acetone was added, and the mixture was allowed to stand to precipitate, separated, and dried. The process of adding acetone, precipitating, separating, and drying was repeated multiple times to finally obtain sodium alginate oxidized powder.
[0059] Example 3
[0060] The difference between Example 3 and Example 1 is that in Example 3, the filter membrane used is the hydrophilic modified polytetrafluoroethylene filter membrane prepared in Preparation Example 3.
[0061] Example 4
[0062] The difference between Example 4 and Example 1 is that in Example 4, the filter membrane used is the hydrophilic modified polytetrafluoroethylene filter membrane prepared in Preparation Example 4.
[0063] Example 5
[0064] The difference between Example 5 and Example 1 is that in Example 5, the molar ratio of sodium alginate to sodium periodate is 1:0.001.
[0065] Example 6
[0066] The difference between Example 6 and Example 1 is that in Example 6, the molar ratio of sodium alginate to sodium periodate is 1:0.05.
[0067] Example 7
[0068] The difference between Example 7 and Example 1 is that in Example 7, the molar ratio of powder A to ethylene glycol is 1:0.001.
[0069] Example 8
[0070] The difference between Example 8 and Example 1 is that in Example 8, the molar ratio of powder A to ethylene glycol is 1:0.05.
[0071] Example 9
[0072] The difference between Example 9 and Example 1 is that in Example 9, phosphoric acid is added to adjust the pH to 3 during the hydrolysis step.
[0073] Example 10
[0074] The difference between Example 10 and Example 1 is that in Example 10, phosphoric acid is added to adjust the pH to 5 during the hydrolysis step.
[0075] Example 11
[0076] The difference between Example 11 and Example 1 is that in Example 11, the filter membrane is a polytetrafluoroethylene filter membrane.
[0077] Comparative Example
[0078] A method for preparing oxidized sodium alginate includes the following steps:
[0079] Oxidation: Sodium alginate was added to water to prepare an 8wt% sodium alginate solution. Sodium periodate solution was added to the sodium alginate solution and mixed evenly. The molar ratio of sodium alginate to sodium periodate was 1:0.03. After reacting at 70℃ for 2 hours, excess ethylene glycol was added to terminate the oxidation reaction.
[0080] Precipitation: Add excess acetone to the solution after the reaction, centrifuge to dehydrate, precipitate, separate and dry to obtain powder A; Filtration: Dissolve powder A in acetone, stir magnetically to form a homogeneous solution, filter the homogeneous solution four times using a filter membrane to obtain filtrate, and after static precipitation, separation and drying, obtain sodium alginate powder. In this embodiment, the filter membrane is the hydrophilic modified polytetrafluoroethylene filter membrane prepared in Preparation Example 1.
[0081] Detection methods
[0082] I. Performance Testing of Oxidized Sodium Alginate
[0083] Sodium oxidized alginate was prepared according to the preparation methods of Examples 1-11. Three groups of sodium oxidized alginate were prepared according to the preparation methods of the comparative examples, and were designated as Comparative Example ①, Comparative Example ②, and Comparative Example ③. The degree of oxidation of powder A and sodium oxidized alginate powder was detected by iodometric titration. At the same time, the protein content in sodium oxidized alginate powder was detected by BCA method and recorded in Table 1.
[0084] Table 1 Test Result Record Sheet
[0085]
[0086]
[0087] Compared with Comparative Examples ①-③, in Examples 1-2, the oxidation degree of powder A was similar to that of sodium alginate oxide. However, in Comparative Examples ①-③, the oxidation degree of sodium alginate oxide increased in Comparative Examples ① and ③ compared to the corresponding oxidation degree of powder A, while it decreased in Comparative Example ②. Furthermore, the difference between the oxidation degree of sodium alginate oxide and that of powder A was relatively large. This indicates that during the subsequent purification and precipitation process of powder A in Comparative Examples ①-③, the oxidation degree of sodium alginate oxide in powder A was affected by environmental factors, resulting in a significant deviation between the oxidation degree of sodium alginate oxide and the initial expectation. Moreover, the change in oxidation degree was random and could not be predicted.
[0088] In Examples 1-2, the oxidation degree of sodium alginate is similar to that of powder A, with little difference. In Examples 1-2, ethylene glycol is used to protect the aldehyde group of sodium alginate. The resulting acetal is stable and not easily denatured or reacted. After hydrolysis of the acetal, the aldehyde group is regenerated, making the oxidation degree of sodium alginate relatively stable and less affected by various factors during purification and precipitation. This results in the oxidation degree of the finished sodium alginate being similar to that of powder A. The oxidation degree of powder A can be controlled by adjusting the molar ratio of sodium alginate to sodium periodate, thereby obtaining sodium alginate with high purity and controllable oxidation degree.
[0089] Compared with Example 1, Examples 3-4 show an increased protein content. In Examples 3-4, the mass ratio of sodium styrene sulfonate to acrylic acid was changed during hydrophilic modification, indicating that this ratio affects the modification effect of the polytetrafluoroethylene (PTFE) filter membrane. Sodium styrene sulfonate and acrylic acid copolymerize to form a hydrophilic copolymer that deposits on the PTFE filter membrane surface. The introduction of sulfonic acid groups on the PTFE filter membrane surface increases its hydrophilicity, thereby improving the adsorption and filtration effect of the hydrophilic modified PTFE filter membrane on proteins. However, changing the mass ratio of sodium styrene sulfonate to acrylic acid alters the amount of copolymer deposition, thus changing the hydrophilic modification effect on the PTFE filter membrane. Consequently, in Examples 3-4, the filtration effect of the filter membrane on proteins deteriorates, and the protein content increases.
[0090] Compared with Example 1, the oxidation degree of Example 5 was reduced and that of Example 6 was increased. In Examples 5-6, the oxidation degree of oxidized sodium alginate and that of powder A showed little difference compared with Example 1. Examples 5-6 changed the molar ratio of sodium alginate to sodium periodate, indicating that the amount of sodium periodate added directly affected the oxidation degree of oxidized sodium alginate. The oxidation degree of oxidized sodium alginate can be changed by adjusting the molar ratio of sodium alginate to sodium periodate.
[0091] Compared with Example 1, in Examples 5 and 6, the oxidation degree of sodium alginate was significantly higher in Example 7 than that of powder A, while the variation in Example 8 was similar to that in Example 1, showing no significant change. This indicates that the molar ratio of powder A to ethylene glycol affects the protective effect of ethylene glycol on the aldehyde groups in sodium alginate. When the amount of ethylene glycol added is low, not all aldehyde groups in sodium alginate are protected, resulting in some aldehyde groups remaining unprotected and affecting subsequent filtration and precipitation processes, thus impacting the oxidation degree of sodium alginate. Conversely, when the amount of ethylene glycol added is high, the selected molar ratio of powder A to ethylene glycol in this application results in an excess of ethylene glycol. Further increasing the amount of ethylene glycol added does not significantly enhance the protective effect on the aldehyde groups.
[0092] Compared with Example 1, the oxidation degree of Example 9 changed less, while in Example 10, the oxidation degree of sodium alginate was lower than that of powder A, indicating that the pH of the solution affects the hydrolysis of acetal. Acetal hydrolyzes to produce aldehydes and alcohols under acidic conditions, and the hydrolysis rate is related to the pH of the solution. As the pH decreases, the hydrolysis rate increases. In Example 10, the increased pH resulted in a lower hydrolysis rate. In the same amount of time, the acetal was not completely hydrolyzed, and some aldehyde groups were not deprotected, thus reducing the oxidation degree of Example 10.
[0093] Compared with Example 1, Example 11 has a higher protein content. The filter membrane in Example 11 is a polytetrafluoroethylene (PTFE) filter membrane. When filtering proteins, the unmodified PTFE filter membrane has high hydrophobicity, which weakens the adsorption and filtration effect of proteins and reduces the antifouling performance. When using this filter membrane for multiple filtrations, the PTFE filter membrane is blocked by impurities, and the filtration effect deteriorates, thus resulting in a higher protein content in Example 11.
[0094] II. Application Testing of Sodium Oxygenated Alginate
[0095] Following the preparation methods of Examples 1-2, oxidized sodium alginate with oxidation degrees of 3% and 5% were prepared, respectively. Using PBS solution at pH 7.4 as a simulated body fluid, and simulating physiological conditions at 37°C, the degradation rates of oxidized sodium alginate with an oxidation degree of 5%, oxidized sodium alginate with an oxidation degree of 3%, and a mixture of oxidized sodium alginate with an oxidation degree of 5% and sodium alginate at a ratio of 1:1-3 were measured. The results are as follows:
[0096] Oxidized sodium alginate with an oxidation degree of 5% degrades in simulated body fluid in one week;
[0097] Oxidized sodium alginate with an oxidation degree of 3% degrades in simulated body fluids over 2.5 weeks;
[0098] A 1:1 mixture of oxidized sodium alginate with 5% oxidation degree and sodium alginate degrades in simulated body fluid in one month.
[0099] Oxidized sodium alginate with an oxidation degree of 5% was mixed with sodium alginate in a 1:3 ratio and degraded in simulated body fluid over 3 months.
[0100] The above results demonstrate that oxidized sodium alginate degrades faster in vivo, making it more suitable for use in the human body as a drug-loaded microsphere, tissue engineering scaffold, and in vivo wound dressing. The degradation rate can be controlled by adjusting the degree of oxidation of the oxidized sodium alginate and the ratio of oxidized sodium alginate to sodium alginate, ensuring that the prepared drug-loaded microspheres, tissue engineering scaffolds, and in vivo wound dressings maintain their required mechanical strength during their action and can naturally degrade within the body after exertion, without affecting human recovery. The oxidized sodium alginate prepared by the method provided in this application meets the specific oxidation degree requirements for oxidized sodium alginate in this application.
[0101] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.
Claims
1. A method for preparing oxidized sodium alginate, characterized in that: Includes the following steps: Oxidation: Add sodium alginate to water to prepare sodium alginate solution, add sodium periodate solution to sodium alginate solution and mix well, react at 50-70℃ for 2-2.2h, and then add excess ethylene glycol to terminate the oxidation reaction. Precipitation: Add excess acetone to the solution after the reaction, centrifuge to dehydrate, precipitate, separate, and dry to obtain powder A; Condensation: After powder A is mixed evenly with ethylene glycol, dry HCl gas is introduced and kept at 14-16℃ for 6-7 hours. Then, chloroform is used for extraction. After the extract is dried, the chloroform is distilled off to obtain powder B. The molar ratio of powder A to ethylene glycol is 1:0.01-0.
02. Filtration: Dissolve powder B in acetone and stir magnetically to form a homogeneous solution. Filter the homogeneous solution multiple times using a filter membrane to obtain filtrate. After static precipitation, separation, and drying, obtain powder C. Hydrolysis: After dissolving powder C in water, phosphoric acid is added to adjust the pH to 3.5-4. After reacting for 1-1.2 hours, excess acetone is added, and the mixture is allowed to stand to precipitate, separated, and dried. The process of adding acetone, precipitating, separating, and drying is repeated multiple times to finally obtain sodium alginate oxidized powder.
2. The method for preparing sodium alginate according to claim 1, characterized in that: The sodium alginate solution contains sodium alginate at a concentration of 8-10 wt%, and the molar ratio of sodium alginate to sodium periodate is 1:0.03-0.
04.
3. The method for preparing sodium alginate according to claim 1, characterized in that: The filter membrane is a hydrophilic modified polytetrafluoroethylene filter membrane.
4. The method for preparing sodium alginate oxide according to claim 3, characterized in that: The method for preparing the hydrophilic modified polytetrafluoroethylene filter membrane includes the following steps: mixing polytetrafluoroethylene filter membrane, sodium styrene sulfonate, sodium bisulfite and water, purging with nitrogen and heating to 55-60°C, slowly and continuously adding acrylic acid and 1.5wt% ammonium persulfate, reacting for 5-5.5 hours, removing the polytetrafluoroethylene filter membrane, washing and drying to obtain the hydrophilic modified polytetrafluoroethylene filter membrane.
5. The method for preparing sodium alginate oxide according to claim 4, characterized in that: The mass ratio of sodium p-styrene sulfonate to acrylic acid is 6:(6.8-7.1), and the concentration of sodium p-styrene sulfonate is 11-12 wt%.
6. The application of sodium alginate oxidized by the method described in any one of claims 1-5, characterized in that: Sodium oxidized alginate, used alone or in combination with sodium alginate, is used to prepare drug-loaded microspheres, tissue engineering scaffolds, and in vivo wound dressings.