Method for preparing modified carrageenan by using slurry method and application of modified carrageenan

Abstract

The invention discloses a method for preparing modified carrageenan by using a slurry method and application of the modified carrageenan. The preparation method comprises the following steps: uniformly mixing potassium salt, deionized water, an oxidizing agent and carrageenan to obtain slurry, preparing modified carrageenan by virtue of a slurry oxidation method, and improving the stability of the modified carrageenan in an oxidative degradation reaction by virtue of electrostatic interaction of potassium ions and sulfate radicals in the carrageenan, so that the content of the sulfate radicals in the modified carrageenan is improved. The single hydrogen peroxide oxidizing agent is adopted, the preparation method is simple, efficient, low in solvent consumption and environmentally friendly, and the prepared modified carrageenan has the dual advantages of low molecular weight and high sulfate radical content and has wide application prospects in the field of anticoagulation.

Description

Technical Field

[0001] The invention relates to the technical field of polysaccharide processing, and in particular to a method for preparing modified carrageenan by a slurry method and application thereof. Background Art

[0002] Carrageenan is a linear sulfated polysaccharide extracted from red algae. Carrageenan is composed of 3-β-D-galactose and 4-linked α-D-galactopyran or 4-linked 3,6-ether-α-D-galactopyran units connected alternately. According to the number and position of sulfate groups in the constituent units and disaccharide units, carrageenan can be roughly divided into kappa (κ), iota (ι), lambda (λ), mu (μ), nu (ν), gamma (γ), alpha (α), delta (δ), theta (θ) and beta (β) carrageenan. Among them, the three most common types of commercial carrageenan are κ, ι and λ carrageenan, with 1, 2 and 3 sulfate groups in each repeating disaccharide unit, respectively.

[0003] The molecular weight of natural carrageenan is about 450,000 to 650,000 Daltons, and it is usually used as a thickener, gelling agent, suspending agent, emulsifier and stabilizer. However, the molecular weight of natural carrageenan is too high, which limits its application to a certain extent. After the natural carrageenan is degraded, low molecular weight carrageenan can be obtained. Compared with the initial carrageenan, low molecular weight carrageenan has better solubility, absorption efficiency and bioavailability. In addition, low molecular weight carrageenan also exhibits good biological activity, including antibacterial, anticoagulant, antioxidant and antiviral properties, which provides the possibility for its application in the medical field. On the other hand, carrageenan contains a large number of negatively charged sulfate groups, which can enhance the affinity of antithrombin III (AT-III) with activated coagulation factors such as thrombin, thereby producing an anticoagulant effect in vivo and in vitro. Therefore, carrageenan can potentially inhibit platelet aggregation. Literature studies have shown that the introduction of sulfate groups can enhance the biological activity of polysaccharides, including antiviral, anticoagulant, antioxidant and antitumor. Therefore, increasing the sulfate concentration can potentially enhance the biological activity and function of carrageenan, thereby expanding its application in antiviral, anticoagulant, antioxidant and antitumor effects. Therefore, it is of great significance to obtain a carrageenan with a low molecular weight and a high sulfate content.

[0004] At present, the methods for obtaining low molecular weight polysaccharides mainly include physical method, enzymatic method and chemical method. The physical method mainly refers to ultrasonic and high temperature degradation method, which has the disadvantage of poor selectivity; the enzymatic method uses biologically active enzymes to split carrageenan macromolecules, but enzyme preparations are often expensive and their activity is easily lost. The chemical method has low cost, simple process and good scalability.

[0005] The chemical method for preparing low molecular weight sulfated polysaccharides mainly includes acid hydrolysis and free radical degradation. Among the free radical degradation methods, the most commonly used one is the transition metal ion combined with H2O2 degradation. Compared with the acid hydrolysis method, the degradation of sulfated polysaccharides by transition metal ions combined with appropriate concentrations of H2O2 can not only reduce the molecular weight, but also effectively avoid the removal of sulfate. 2+ -H2O2 system is one of the most widely used degradation methods. 2+ -H2O2 system can effectively degrade fucoidan and increase its sulfate content; however, the concentration of fucoidan in this reaction system can only reach 6.67% (w / v), and the reaction efficiency is low (Study on the chemical composition and activity of kelp fucoidan sulfate, publication date: 20040610; Research progress on the preparation of low molecular weight fucoidan and fucoidan oligosaccharides by chemical degradation of fucoidan, publication date: 20240719). In addition, Cu 2+ It is toxic and poses certain safety risks.

[0006] Although reducing the molecular weight of sulfated polysaccharides plays an important role in improving biological activity, some studies have reported that the anticoagulant activity of degraded fucoidan sulfate with a molecular weight of about 2kDa is significantly lower than that of degraded fucoidan sulfate with a molecular weight of 8kDa and 200kDa (Study on the Chemical Composition and Activity of Kelp Fucoidan Sulfate, Publication Date: 20040610). For carrageenan, the results also show that the molecular weight of partially oxidized carrageenan is higher than that of fully oxidized carrageenan, but partially oxidized carrageenan exhibits better anticoagulant effect than fully oxidized carrageenan (PMID: 30925999). It can be seen that sulfated polysaccharides or carrageenan with a moderate molecular weight have a better anticoagulant effect.

[0007] Therefore, it is of great significance to develop a method that can prepare carrageenan with low molecular weight and high sulfate content while ensuring its anticoagulant activity. Summary of the invention

[0008] In order to overcome the above defects and shortcomings in the prior art, the present invention provides a method for preparing modified carrageenan by a slurry process and its application.

[0009] The first object of the present invention is to provide a method for preparing modified carrageenan at a high concentration by using a slurry process.

[0010] The second object of the present invention is to provide modified carrageenan prepared by the above method.

[0011] The third object of the present invention is to provide the use of the modified carrageenan in the preparation of anticoagulants.

[0012] Therefore, the present invention claims the following:

[0013] A method for preparing modified carrageenan by a slurry method comprises fully mixing potassium salt, water, an oxidant and carrageenan to obtain a slurry, and then reacting and purifying.

[0014] Preferably, the mass volume ratio of the carrageenan, water and potassium salt is 4 g: (0-16) mL: (4-400) mg.

[0015] More preferably, the water is deionized water.

[0016] Preferably, the potassium salt is any one of potassium sulfate, potassium nitrate or potassium dihydrogen phosphate.

[0017] Preferably, the sufficient mixing to obtain the slurry is carried out at 15-40°C.

[0018] More preferably, the sufficient mixing to obtain the slurry is carried out at 30°C.

[0019] Preferably, the reaction is carried out at 64-66° C. for 35-45 min, or at 24-26° C. for 890-910 min.

[0020] More preferably, the reaction is carried out at 65° C. for 40 min, or at 25° C. for 900 min.

[0021] Preferably, the carrageenan is iota-carrageenan, Kappa-carrageenan or Lambda-carrageenan.

[0022] Preferably, the oxidant is a hydrogen peroxide solution with a mass fraction of 28-32%.

[0023] More preferably, the oxidant is a hydrogen peroxide solution with a mass fraction of 30%.

[0024] Preferably, the mass volume ratio of the carrageenan to the hydrogen peroxide solution is 4 g: (8-26.7) mL.

[0025] Further preferably, the carrageenan is iota-carrageenan, the mass volume ratio of the iota-carrageenan, water, potassium salt and hydrogen peroxide solution is 4g: (0-16) mL: 4mg: (8-26.7) mL, the potassium salt is any one of potassium sulfate, potassium nitrate or potassium dihydrogen phosphate, and the reaction is carried out at 65°C for 40 minutes;

[0026] Or the carrageenan is iota-carrageenan, the mass volume ratio of the iota-carrageenan, water, potassium salt and hydrogen peroxide solution is 4g: (0-16) mL: 40mg: (8-26.7) mL, the potassium salt is potassium nitrate, and the reaction is carried out at 65°C for 40 minutes;

[0027] Under this preferred embodiment, compared with unmodified iota-carrageenan, the sulfate content of the prepared modified iota-carrageenan is increased by 29.7-47.1%, and the viscosity average molecular weight is reduced by 83.2-95.3%.

[0028] Further preferably, the carrageenan is Kappa-carrageenan, the mass volume ratio of the Kappa-carrageenan, water, potassium salt and hydrogen peroxide solution is 4g:8mL:4mg:16mL, the potassium salt is potassium sulfate, and the reaction is carried out at 65°C for 40min. Under this preferred embodiment, compared with the unmodified Kappa-carrageenan, the sulfate content of the prepared modified Kappa-carrageenan is increased by 27.3%, and the viscosity average molecular weight is reduced by 91.2%.

[0029] Further preferably, the carrageenan is lambda-carrageenan, the mass volume ratio of the lambda-carrageenan, water, potassium salt and hydrogen peroxide solution is 4g:8mL:4mg:16mL, the potassium salt is potassium sulfate, and the reaction is carried out at 65°C for 40min. Under this preferred embodiment, compared with the unmodified lambda-carrageenan, the sulfate content of the prepared modified lambda-carrageenan is increased by 63.0%, and the viscosity average molecular weight is reduced by 46.2%.

[0030] Preferably, the purification comprises removal of potassium ions using a chelating agent, dialysis, filtration and drying.

[0031] As an practicable manner, the chelating agent is sodium tetraphenylborate.

[0032] Preferably, the usage ratio of the sodium tetraphenylborate to the potassium salt is 0.2 mol: (4-400) g.

[0033] Compared with the commonly used homogeneous aqueous solution degradation method in the prior art (in which carrageenan usually needs to be dissolved in a high-temperature aqueous solution above 90°C), the present invention adopts a heterogeneous slurry method. In the method of the present invention:

[0034] (1) Carrageenan powder is directly mixed with a solution prepared by mixing potassium salt, deionized water and 30% by mass hydrogen peroxide solution. High temperature is not used to dissolve the carrageenan. As the oxidation reaction proceeds, the molecular weight of the carrageenan is significantly reduced and it will spontaneously dissolve during the dialysis purification process, thereby greatly saving heat energy.

[0035] (2) In the homogeneous aqueous solution degradation method, Kappa-carrageenan and iota-carrageenan will spontaneously react with the introduced potassium ions to form large cross-linked hydrogels, resulting in the inability to effectively remove the residual potassium ions and perform dialysis purification of the modified carrageenan. The slurry method of the present invention effectively solves the technical problem of the spontaneous formation of cross-linked hydrogels by the introduced potassium ions and Kappa-carrageenan and iota-carrageenan.

[0036] (3) The concentration of reactants in the slurry method is high and the amount of solvent used is small, that is, the solid-liquid ratio is high, and the reaction efficiency is significantly improved.

[0037] The modified carrageenan is prepared by any of the above methods.

[0038] Application of the modified carrageenan in the preparation of anticoagulants.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] The present invention discloses a method for preparing modified carrageenan by a slurry method and its application. The present invention mixes potassium salt, deionized water, an oxidant and carrageenan to obtain a slurry, prepares the modified carrageenan by a slurry oxidation method, and improves its stability in an oxidative degradation reaction by the electrostatic interaction between potassium ions and sulfate groups in the carrageenan, thereby increasing the sulfate content in the modified carrageenan. The present invention adopts a single hydrogen peroxide oxidation agent, the preparation method is simple and efficient, the solvent consumption is low, and it is green and environmentally friendly. The prepared modified carrageenan has the dual advantages of low molecular weight and high sulfate content, and has a wide range of application prospects in the field of anticoagulation. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is the state of the modified iota-carrageenan prepared in Comparative Example 7 after cooling.

[0042] Figure 2 This is the state of the modified iota-carrageenan prepared in Comparative Example 8 after cooling.

[0043] Figure 3 This is the state of the modified iota-carrageenan prepared in Comparative Example 9 after cooling.

[0044] Figure 4 This is the state of the modified iota-carrageenan prepared in Comparative Example 10 after cooling.

[0045] Figure 5 This is the state of the modified iota-carrageenan prepared in Comparative Example 11 after cooling.

[0046] Figure 6 This is the state of the modified Kappa-carrageenan prepared in Comparative Example 12 after cooling.

[0047] Figure 7 This is the state of the modified Kappa-carrageenan prepared in Comparative Example 13 after cooling.

[0048] Figure 8 This is the state of the modified iota-carrageenan prepared in Comparative Example 14 during the reaction.

[0049] Fig. 9 This is the state of the modified iota-carrageenan prepared in Comparative Example 14 after cooling.

[0050] Fig.10 This is the state of the modified Kappa-carrageenan prepared in Comparative Example 15 after cooling.

[0051] Fig.11 This is the state of the modified Lambda-carrageenan prepared in Comparative Example 16 during the reaction.

[0052] Fig.12 This is the state of the modified Lambda-carrageenan prepared in Comparative Example 16 after cooling.

[0053] Fig.13 The states of 8%, 9%, and 10% Lambda-carrageenan solutions (w / v) when cooled to 75°C. DETAILED DESCRIPTION

[0054] The present invention is further described below with reference to specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0055] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0056] Example 1 Preparation of modified iota-carrageenan

[0057] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.005 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0058] Example 2 Preparation of modified iota-carrageenan

[0059] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 40 mg of potassium sulfate, stir rapidly at 40°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.025 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0060] Example 3 Preparation of modified iota-carrageenan

[0061] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 400 mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.025 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0062] Example 4 Preparation of modified iota-carrageenan

[0063] Weigh 4g of iota-carrageenan powder in a beaker, then add a solution of 8mL of deionized water, 16mL of 30% hydrogen peroxide solution (w / v) and 4mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, put the beaker into a 25°C water bath, and react for 900min. After the reaction is completed, add 40mL of 0.005mol / L sodium tetraphenylborate solution and stir for 30min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0064] Example 5 Preparation of modified iota-carrageenan

[0065] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of potassium nitrate, stir rapidly at 15°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.005 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0066] Example 6 Preparation of modified iota-carrageenan

[0067] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 40 mg of potassium nitrate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.025 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0068] Example 7 Preparation of modified iota-carrageenan

[0069] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 400 mg of potassium nitrate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.025 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0070] Example 8 Preparation of modified iota-carrageenan

[0071] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of potassium nitrate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 25°C water bath, and react for 900 min. After the reaction is completed, add 40 mL of 0.005 mol / L sodium tetraphenylborate solution and stir for 30 min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0072] Example 9 Preparation of modified iota-carrageenan

[0073] Weigh 4g of iota-carrageenan powder in a beaker, then add a solution of 8mL of deionized water, 16mL of 30% hydrogen peroxide solution (w / v) and 4mg of potassium dihydrogen phosphate, stir rapidly at 30°C to obtain a slurry mixture, put the beaker into a 65°C water bath and react for 40min. After the reaction is completed, add 40mL of 0.005mol / L sodium tetraphenylborate solution and stir for 30min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0074] Example 10 Preparation of modified iota-carrageenan

[0075] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 40 mg of potassium dihydrogen phosphate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.025 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0076] Example 11 Preparation of modified iota-carrageenan

[0077] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 400 mg of potassium dihydrogen phosphate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.025 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0078] Example 12 Preparation of modified iota-carrageenan

[0079] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of potassium dihydrogen phosphate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 25°C water bath, and react for 900 min. After the reaction is completed, add 40 mL of 0.005 mol / L sodium tetraphenylborate solution and stir for 30 min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0080] Example 13 Preparation of Modified Kappa-Carrageenan

[0081] Weigh 4g of Kappa-carrageenan powder in a beaker, then add a solution of 8mL of deionized water, 16mL of 30% hydrogen peroxide solution (w / v) and 4mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, put the beaker into a 65°C water bath, and react for 40min. After the reaction is completed, add 40mL of 0.005mol / L sodium tetraphenylborate solution and stir for 30min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is replaced three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified Kappa-carrageenan.

[0082] Example 14 Preparation of modified Kappa-carrageenan

[0083] Weigh 4g of Kappa-carrageenan powder in a beaker, then add a solution of 8mL of deionized water, 16mL of 30% hydrogen peroxide solution (w / v) and 4mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, put the beaker into a 25°C water bath, and react for 900min. After the reaction is completed, add 40mL of 0.005mol / L sodium tetraphenylborate solution and stir for 30min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is replaced three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified Kappa-carrageenan.

[0084] Example 15 Preparation of modified Lambda-carrageenan

[0085] Weigh 4g Lambda-carrageenan powder in a beaker, then add a solution of 8mL deionized water, 16mL 30% hydrogen peroxide solution (w / v) and 4mg potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, put the beaker into a 65°C water bath, and react for 40min. After the reaction is completed, add 40mL 0.005mol / L sodium tetraphenylborate solution and stir for 30min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is replaced three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified Lambda-carrageenan.

[0086] Example 16 Preparation of modified Lambda-carrageenan

[0087] Weigh 4g Lambda-carrageenan powder in a beaker, then add a solution of 8mL deionized water, 16mL 30% hydrogen peroxide solution (w / v) and 4mg potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, put the beaker into a 25°C water bath, and react for 900min. After the reaction is completed, add 40mL 0.005mol / L sodium tetraphenylborate solution and stir for 30min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is replaced three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified Lambda-carrageenan.

[0088] Example 17 Preparation of modified iota-carrageenan

[0089] Weigh 4g of iota-carrageenan powder in a beaker, then add a solution of 16mL of deionized water, 8mL of 30% hydrogen peroxide solution (w / v) and 4mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, put the beaker into a 65°C water bath and react for 40min. After the reaction is completed, add 40mL of 0.005mol / L sodium tetraphenylborate solution and stir for 30min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0090] Example 18 Preparation of modified iota-carrageenan

[0091] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 24 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, and place the beaker in a 65°C water bath for 40 minutes. After the reaction is completed, add 40 mL of 0.005 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0092] Example 19 Preparation of modified iota-carrageenan

[0093] Weigh 4g of iota-carrageenan powder in a beaker, then add a solution of 6.7mL of deionized water, 13.3mL of 30% hydrogen peroxide solution (w / v) and 4mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, put the beaker into a 65°C water bath, and react for 40min. After the reaction is completed, add 40mL of 0.005mol / L sodium tetraphenylborate solution and stir for 30min to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0094] Example 20 Preparation of modified iota-carrageenan

[0095] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 13.3 mL of deionized water, 26.7 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of potassium sulfate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.005 mol / L sodium tetraphenylborate solution and stir for 30 minutes to obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is changed three times a day. After dialysis, it is filtered to remove the solid particles of potassium tetraphenylborate, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0096] Comparative Example 1

[0097] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of copper acetate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.05 mol / L NaOH solution and stir for 30 minutes, adjust the pH to neutral with acetic acid, and obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is replaced three times a day. After dialysis, it is filtered to remove copper hydroxide solid particles, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0098] Comparative Example 2

[0099] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 40 mg of copper acetate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, and react for 40 minutes. After the reaction is completed, add 40 mL of 0.1 mol / L NaOH solution and stir for 30 minutes, adjust the pH to neutral with acetic acid, and obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is replaced three times a day. After dialysis, it is filtered to remove copper hydroxide solid particles, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0100] Comparative Example 3

[0101] Weigh 4 g of iota-carrageenan powder in a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of copper acetate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 25°C water bath, and react for 900 min. After the reaction is completed, add 40 mL of 0.05 mol / L NaOH solution and stir for 30 min, adjust the pH to neutral with acetic acid, and obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, and the external deionized water is replaced three times a day. After dialysis, it is filtered to remove copper hydroxide solid particles, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0102] Comparative Example 4

[0103] Weigh 4 g of iota-carrageenan powder into a beaker, then add a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 4 mg of sodium sulfate, stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, react for 40 minutes, and obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, the external deionized water is replaced three times a day, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0104] Comparative Example 5

[0105] 4 g of iota-carrageenan powder was weighed into a beaker, and then a solution of 8 mL of deionized water, 16 mL of 30% hydrogen peroxide solution (w / v) and 40 mg of sodium sulfate was added, and the mixture was rapidly stirred at 30°C to obtain a slurry mixture. The beaker was placed in a water bath at 25°C and reacted for 900 min to obtain a mixed slurry. The obtained mixed slurry was dialyzed with deionized water for three days, and the external deionized water was replaced three times a day, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0106] Comparative Example 6

[0107] Weigh 4 g of iota-carrageenan powder in a beaker, then add 8 mL of deionized water and 16 mL of 30% hydrogen peroxide solution (w / v), stir rapidly at 30°C to obtain a slurry mixture, place the beaker in a 65°C water bath, react for 40 minutes, and obtain a mixed slurry. The obtained mixed slurry is dialyzed with deionized water for three days, the external deionized water is replaced three times a day, and then freeze-dried for two days to obtain modified iota-carrageenan.

[0108] Performance Test 1

[0109] 1. Experimental Methods

[0110] Standard solution: prepare 0μg / mL, 20μg / mL, 40μg / mL, 60μg / mL, and 80μg / mL Na2SO4 standard solutions;

[0111] Agarose-BaCl2 reagent: Prepare a 0.01% agarose solution (w / v), add 0.5 g BaCl2 to 100 mL agarose solution, and store in a 4°C refrigerator overnight.

[0112] Prepare 1mg / mL sample solution (solvent is 0.1M HCl solution) and hydrolyze at 90℃ for 6h. Take 1.1mL of the hydrolyzed sample solution, add 1.2mL 8% trichloroacetic acid solution (w / v) and 0.6mL agarose-BaCl2 reagent, mix well and let stand for 35min, use water as a control, and measure the absorbance at a wavelength of 500nm. Shake the sample solution before testing.

[0113] Test the prepared standard solution according to the above test method, record the absorbance, draw the standard curve, and obtain the regression equation. Substitute the absorbance value of the sample into the regression equation to obtain the sulfate content.

[0114] Each sample was measured three times and the average value was taken as the final result. The blank samples were unmodified iota-carrageenan, Kappa-carrageenan and Lambda-carrageenan.

[0115] 2. Experimental Results

[0116] The results are shown in Table 1. As can be seen from Table 1, the sulfate content of the modified carrageenan prepared in Examples 1 to 20 is higher than that of the unmodified carrageenan, and different types of potassium salts have different degrees of influence on the improvement of sulfate content. Compared with the unmodified iota-carrageenan, the modified iota-carrageenan prepared by modifying carrageenan with potassium sulfate and hydrogen peroxide has the most obvious improvement effect, and the sulfate content is increased by up to 47.1% compared with the unmodified iota-carrageenan. The sulfate content of the modified iota-carrageenan prepared by modifying iota-carrageenan with copper ions and hydrogen peroxide is not much different from that of the unmodified iota-carrageenan.

[0117] In addition to potassium sulfate, potassium nitrate and potassium dihydrogen phosphate can also increase the sulfate content in modified iota-carrageenan. The best improvement effect is achieved when the mass volume ratio of carrageenan powder, deionized water, potassium salt and hydrogen peroxide solution is 1g:2mL:1mg:4mL.

[0118] Potassium ions also play a positive role in increasing the sulfate content in modified Kappa-carrageenan and modified Lambda-carrageenan. Kappa-carrageenan and Lambda-carrageenan were modified using potassium sulfate and hydrogen peroxide, respectively. When the mass volume ratio of carrageenan powder, deionized water, potassium salt and hydrogen peroxide solution was 1g:2mL:1mg:4mL, the sulfate content of modified Kappa-carrageenan and modified Lambda-carrageenan increased by 27.3% and 63.0% compared with unmodified Kappa-carrageenan and unmodified Lambda-carrageenan.

[0119] The above results show that the sulfate content in the modified carrageenan can be greatly increased by modifying carrageenan with potassium salt and hydrogen peroxide.

[0120] Table 1 Sulfate content of modified carrageenan prepared in Examples 1 to 20 and Comparative Examples 1 to 6

[0121] Group Sulfate content / w% Group Sulfate content / w% Example 1 38.84±0.02 Example 16 33.14±0.04 Example 2 27.93±0.10 Embodiment 17 36.59±0.14 Example 3 27.69±0.04 Embodiment 18 34.23±0.11 Example 4 30.12±0.05 Embodiment 19 36.74±0.09 Example 5 37.16±0.11 Embodiment 20 36.42±0.06 Example 6 36.79±0.08 Comparative Example 1 24.95±0.13 Example 7 28.63±0.10 Comparative Example 2 22.49±0.29 Example 8 30.41±0.08 Comparative Example 3 19.97±0.16 Example 9 38.30±0.16 Comparative Example 4 24.22±0.17 Example 10 30.62±0.19 Comparative Example 5 25.39±0.22 Embodiment 11 27.43±0.21 Comparative Example 6 25.01±0.09 Example 12 28.32±0.18 Unmodified iota-carrageenan 26.40±0.05 Embodiment 13 26.45±0.14 Unmodified Kappa-Carrageenan 20.78±0.07 Embodiment 14 22.78±0.02 Unmodified Lambda-Carrageenan 24.62±0.05 Embodiment 15 40.12±0.05

[0122] Performance Test 2

[0123] 1. Experimental Methods

[0124] The viscosity average molecular weight (Mη) of modified carrageenan was measured using the viscosity method in 0.7% Na2SO4 aqueous solution (w / v) at 35±0.1°C. Under certain temperature and solvent conditions, the relationship between the intrinsic viscosity [η] and the polymer molar mass M is the Mark-Houwink empirical equation:

[0125]

[0126] The viscosity average molecular weight of the modified carrageenan was measured using an Ubbelohde viscometer. The carrageenan was dissolved in a 0.7% Na2SO4 aqueous solution (w / v) as a solvent with a concentration of 0.1 to 0.2% (w / v) and the temperature was maintained at 35±0.1°C.

[0127] According to experiments, in a sufficiently dilute polymer solution, there is the following empirical formula:

[0128]

[0129] Where κ and β are called Huggins and Kramer constants, respectively.

[0130] Because the measurement is usually carried out in a dilute solution, the density of the solution is approximately equal to the density of the solvent, so η r Written as:

[0131]

[0132] t is the time it takes for the liquid surface to flow from scale a to scale b when measuring the viscosity of the solution; t0 is the time it takes for the pure solvent to flow through; so by measuring the outflow time of the solvent and solution in the capillary, η is obtained from the above formula r , and then calculate [η] by extrapolation.

[0133] The blank samples were unmodified iota-carrageenan, Kappa-carrageenan and Lambda-carrageenan.

[0134] 2. Experimental Results

[0135] The results are shown in Table 2. The original Mη of unmodified iota-carrageenan, Kappa-carrageenan and Lambda-carrageenan were 558.271±0.970 kDa, 610.194±0.617 kDa and 1133.247±6.098 kDa, respectively. Compared with unmodified carrageenan, the molecular weight of the modified carrageenan prepared by modifying carrageenan with potassium salt and hydrogen peroxide was significantly reduced.

[0136] Although the molecular weight of the modified iota-carrageenan prepared by modifying iota-carrageenan with copper ions and hydrogen peroxide can be reduced to less than 10 kDa, the modified carrageenan within this molecular weight range has poor stability due to its small molecular weight. It easily absorbs moisture and turns brown when left for a long time, and browning may be a deterioration phenomenon of carrageenan.

[0137] Further, according to the prior art disclosure (Study on the Chemical Composition and Activity of Kelp Fucoidan Sulfate, Publication Date: 20040610; PMID: 30925999, Publication Date: 20190319), a too small molecular weight of carrageenan will also affect its anticoagulant activity. Therefore, the small molecular weight modified iota-carrageenan prepared by using copper ions and hydrogen peroxide not only has deterioration, but also may affect its anticoagulant performance, while the modified carrageenan prepared by Examples 1 to 20 of the present invention not only has a high sulfate content, but also has a moderate molecular weight, does not have the above-mentioned disadvantages, and has a good application prospect in the preparation of anticoagulants.

[0138] Table 2 Molecular weight of modified carrageenan prepared in Examples 1 to 20 and Comparative Examples 1 to 6

[0139] Group Mη(KDa) Group Mη(KDa) Example 1 73.593±0.204 Example 16 594.170±3.063 Example 2 17.293±0.028 Embodiment 17 48.461±0.938 Example 3 21.490±0.026 Embodiment 18 53.668±0.250 Example 4 77.839±0.060 Embodiment 19 48.355±0.138 Example 5 65.024±0.018 Embodiment 20 26.257±0.189 Example 6 93.523±0.488 Comparative Example 1 2.148±0.144 Example 7 110.292±0.292 Comparative Example 2 2.321±0.132 Example 8 69.362±0.101 Comparative Example 3 3.602±0.030 Example 9 50.683±0.336 Comparative Example 4 80.049±0.504 Example 10 155.715±0.377 Comparative Example 5 95.704±1.298 Embodiment 11 60.141±0.166 Comparative Example 6 156.746±0.158 Example 12 75.867±0.059 Unmodified iota-carrageenan 558.271±0.970 Embodiment 13 53.438±0.509 Unmodified Kappa-Carrageenan 610.194±0.617 Embodiment 14 153.892±0.560 Unmodified Lambda-Carrageenan 1133.247±6.098 Embodiment 15 609.608±2.045

[0140] Comparative Example 7

[0141] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified iota-carrageenan:

[0142] Weigh 1.00g iota-carrageenan powder and dissolve it in 50.00mL deionized water to obtain a 2% carrageenan solution (w / v). Then add a solution of 2mL deionized water, 4mL 30% hydrogen peroxide solution (w / v) and 1mg potassium sulfate. Place the beaker in a 65℃ water bath and react for 40min. After the reaction is completed, cool to room temperature and find that the system is in a soft gel state with strong fluidity ( Figure 1 ).

[0143] Comparative Example 8

[0144] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified iota-carrageenan:

[0145] Weigh 1.00g iota-carrageenan powder and dissolve it in 50.00mL deionized water to obtain a 2% carrageenan solution (w / v). Then add a solution of 2mL deionized water, 4mL 30% hydrogen peroxide solution (w / v) and 10mg potassium sulfate. Place the beaker in a 65℃ water bath and react for 40min. After the reaction is completed and cooled to room temperature, the system is found to be in a soft gel state with average fluidity ( Figure 2 ).

[0146] Comparative Example 9

[0147] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified iota-carrageenan:

[0148] Weigh 1.00g iota-carrageenan powder and dissolve it in 50.00mL deionized water to obtain a 2% carrageenan solution (w / v). Then add a solution mixed with 2mL deionized water, 4mL 30% hydrogen peroxide solution (w / v) and 100mg potassium sulfate. Place the beaker in a 65℃ water bath and react for 40min. After the reaction is completed and cooled to room temperature, the system is found to be in a soft gel state with weak fluidity ( Figure 3 ).

[0149] Comparative Example 10

[0150] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified iota-carrageenan:

[0151] Weigh 2.50g iota-carrageenan powder and dissolve it in 50.00mL deionized water to obtain a 5% carrageenan solution (w / v). Then add a solution of 5mL deionized water, 10mL 30% hydrogen peroxide solution (w / v) and 25mg potassium sulfate. Place the beaker in a 65℃ water bath and react for 40min. After the reaction is completed and cooled to room temperature, the system is found to be a block-like soft gel, but without fluidity ( Figure 4 ).

[0152] Comparative Example 11

[0153] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified iota-carrageenan:

[0154] Weigh 5.00g of iota-carrageenan powder and dissolve it in 50.00mL of deionized water to obtain a 10% carrageenan solution (w / v), then add a solution mixed with 10mL of deionized water, 20mL of 30% hydrogen peroxide solution (w / v) and 50mg of potassium sulfate, put the beaker into a 65°C water bath, and react for 40 minutes. After the reaction is completed and cooled to room temperature, it is found that the system is a block-shaped soft gel with no fluidity. Since the concentration of homogeneously dissolved carrageenan is high (reaching 10%, w / v), it can only be completely dissolved under high temperature conditions, and the partial gelation of the solution occurs quickly after the heating is stopped. The addition of hydrogen peroxide-potassium sulfate solution exacerbates the gelation phenomenon, making it difficult to achieve a complete homogeneous reaction ( Figure 5 ).

[0155] Comparative Example 12

[0156] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified Kappa-carrageenan:

[0157] Weigh 1.00g of Kappa-carrageenan powder and dissolve it in 50.00mL of deionized water to obtain a 2% carrageenan solution (w / v). Then add a solution of 2mL of deionized water, 4mL of 30% hydrogen peroxide solution (w / v) and 1mg of potassium sulfate. Place the beaker in a 65℃ water bath and react for 40min. After the reaction is completed, cool to room temperature. The system is a block-like hard gel with no fluidity ( Figure 6 ).

[0158] Comparative Example 13

[0159] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified Kappa-carrageenan:

[0160] Weigh 1.00g of Kappa-carrageenan powder and dissolve it in 50.00mL of deionized water to obtain a 2% carrageenan solution (w / v). Then add a solution of 2mL of deionized water, 4mL of 30% hydrogen peroxide solution (w / v) and 10mg of potassium sulfate. Place the beaker in a 65℃ water bath and react for 40min. After the reaction is completed, cool to room temperature. The system is a block-like hard gel with no fluidity ( Figure 7 ).

[0161] Comparative Example 14

[0162] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified iota-carrageenan:

[0163] Weigh 2.50g iota-carrageenan powder and dissolve it in 50.00mL deionized water to obtain a 5% carrageenan solution (w / v). Then add a solution of 5mL deionized water, 10mL 30% hydrogen peroxide solution (w / v) and 25mg potassium sulfate. Place the beaker in a 70℃ water bath and react for 40min. After the reaction is completed and cooled to room temperature, the system is a block-like flexible gel with no fluidity ( Figure 8 and Fig. 9 ).

[0164] Comparative Example 15

[0165] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified Kappa-carrageenan:

[0166] Weigh 2.50g Kappa-carrageenan powder and dissolve it in 50.00mL deionized water to obtain a 5% carrageenan solution (w / v). Then add a solution of 2mL deionized water, 4mL 30% hydrogen peroxide solution (w / v) and 25mg potassium sulfate. Place the beaker in a 75℃ water bath and react for 40min. After the reaction is completed, cool to room temperature. The system is a block-like hard gel with no fluidity ( Fig.10 ).

[0167] Comparative Example 16

[0168] Different from the slurry method used in Examples 1 to 20, this comparative example uses a homogeneous aqueous solution degradation method to prepare modified Lambda-carrageenan:

[0169] Weigh 2.50g Lambda-carrageenan powder and dissolve it in 50.00mL deionized water to obtain a 5% carrageenan solution (w / v). Then add a solution of 5mL deionized water, 10mL 30% hydrogen peroxide solution (w / v) and 25mg potassium sulfate. Place the beaker in a 75℃ water bath and react for 40min. After the reaction is completed, cool to room temperature and the system is in a solution state ( Fig.11 and Fig.12 ).

[0170] The homogeneous aqueous solution degradation method in Comparative Examples 7 to 16 requires a long period of high temperature of 90° C. to completely dissolve iota-carrageenan, Kappa-carrageenan and Lambda-carrageenan, and this process consumes a lot of energy.

[0171] Comparative Examples 7 to 15 show that when the concentration of iota-carrageenan and Kappa-carrageenan solution is increased to 5% (w / v), and when the temperature is reduced to 65-75°C, iota-carrageenan and Kappa-carrageenan will form large macroscopic gels, which cannot be effectively mixed with hydrogen peroxide-potassium salt solution. Moreover, the large gel after the reaction cannot be directly dialyzed and purified due to its large volume. It needs to be divided into small pieces before purification, which is not conducive to large-scale preparation. When the concentration of iota-carrageenan and Kappa-carrageenan solution is further increased to 10% (w / v), the gelation process is further aggravated, and it takes a long time to completely dissolve under the dissolution condition of 90°C. After stopping heating, the solution is rapidly gelled, the system is uneven, and the addition of hydrogen peroxide-potassium sulfate solution aggravates the gelation phenomenon. After cooling, a non-fluid gel state is formed, which makes it difficult to achieve complete homogeneous reaction and subsequent purification.

[0172] Comparative Example 16 shows that although 5% Lambda-carrageenan (w / v) is in a solution state after the reaction, Lambda-carrageenan has a large viscosity and exhibits poor fluidity during the reaction. However, 8%, 9%, and 10% Lambda-carrageenan solutions (w / v) have no fluidity at 75°C ( Fig.13 ), cannot be mixed evenly, and cannot effectively mix and react.

[0173] However, under the same conditions, in the slurry process, the concentration of iota-carrageenan, Kappa-carrageenan and Lambda-carrageenan in the hydrogen peroxide-potassium salt solution is usually 10% to 20% (w / v).

[0174] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for preparing modified carrageenan by slurry method, characterized in that: The potassium salt, water, oxidant and carrageenan are thoroughly mixed to obtain a slurry, which is then reacted and purified.

2. The method according to claim 1, characterized in that The oxidant is a hydrogen peroxide solution with a mass fraction of 28-32%.

3. The method according to claim 1, characterized in that The mass volume ratio of the carrageenan, water and potassium salt is 4g: (0-16)mL: (4-400)mg.

4. The method according to claim 2, characterized in that: The mass volume ratio of the carrageenan and the hydrogen peroxide solution is 4 g: (8-26.7) mL.

5. The method according to claim 1, characterized in that The potassium salt is any one of potassium sulfate, potassium nitrate or potassium dihydrogen phosphate.

6. The method according to claim 1, characterized in that The sufficient mixing to obtain the slurry is carried out at 15-40°C.

7. The method according to claim 1, characterized in that The reaction is carried out at 64-66° C. for 35-45 minutes, or at 24-26° C. for 890-910 minutes.

8. The method according to claim 1, characterized in that The carrageenan is iota-carrageenan, Kappa-carrageenan or Lambda-carrageenan.

9. The modified carrageenan prepared by the method according to any one of claims 1 to 8.

10. Use of the modified carrageenan according to claim 9 in the preparation of an anticoagulant.

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