CN116531550A - Preparation method, product and application of cationized alginic acid hemostatic material - Google Patents

Abstract

The invention discloses a preparation method of a cationized alginic acid hemostatic material, wherein alginic acid or alginate and epichlorohydrin and N, N-dimethyl x alkyl tertiary amine are reacted by a one-pot method, x=10-14, the reaction temperature is 30-70 ℃, and the reaction time is 10-60 hours; the mol ratio of the epoxy chloropropane to the N, N-dimethyl x alkyl tertiary amine is 10:11-10:13; the charging mole ratio of alginic acid or alginate to epichlorohydrin is 1:0.5-1:1.5; after the reaction is finished, the precipitate obtained by stirring and reacting with electrolyte solution with the concentration of 50-80% is used for disentangling molecular chains to obtain a foamed product, and the product is precipitated and washed by absolute ethyl alcohol to obtain the cationized alginic acid hemostatic material. The material has better procoagulant property and simultaneously keeps good blood compatibility, and can be widely applied to the field of medical hemostatic products. And can also be applied to the preparation of temperature-sensitive hemostatic gel products.

Description

Preparation method, product and application of a cationic alginic acid hemostatic material

technical field

The invention belongs to the field of hemostatic materials, and relates to a preparation method, product and application of a cationic alginic acid hemostatic material.

Background technique

Hemostatic materials and medical hemostatic products are very important in dealing with traumatic bleeding caused by traffic accidents, natural disasters, surgical operations, etc. Alginic acid and alginate, as a plant-derived polysaccharide, are green, safe, and water-retaining , cheap and easy to get and other characteristics, making it a hot material for people to study. The Chinese invention patent publication with the publication number CN201910591877.5 discloses a sodium alginate quaternary ammonium salt hemostatic antibacterial agent, which is obtained by grafting sodium alginate with an alkyl chain quaternary ammonium salt, and has a good hemostatic effect. Its characteristics try to synthesize the positively charged epoxy alkyl chain quaternary ammonium salt or halogenated alkyl quaternary ammonium salt, and then graft the quaternary ammonium salt on the negatively charged sodium alginate polysaccharide. However, this method needs to first synthesize the quaternary ammonium salt, and then graft the quaternary ammonium salt on the sodium alginate, and the steps are relatively complicated. Therefore, it is necessary to provide an alginic acid material with simple synthesis and hemostatic properties.

Contents of the invention

In view of this, the present invention provides a preparation method, product and application of a cationic alginic acid hemostatic material. The present invention specifically provides the following technical solutions:

1. A preparation method of a cationic alginic acid hemostatic material, the preparation steps are:

1) One-pot reaction of alginic acid or alginate with epichlorohydrin, N,N-dimethyl x alkyl tertiary amine, said x=10～14, the reaction of said one-pot reaction The temperature is 30-70°C, and the reaction time is 10-60 hours; the molar ratio of epichlorohydrin to N,N-dimethylxyl tertiary amine is 10:11-10:13; the The molar ratio of alginic acid or alginate to epichlorohydrin is 1:0.5～1:1.5;

2) After the reaction is over, stir the precipitate obtained by the reaction with an electrolyte solution with a concentration of 50% to 80%, untie the entanglement of molecular chains, and obtain a foamed product, precipitate and wash with absolute ethanol to obtain cationized seaweed Acid hemostatic material.

Further, the product obtained in step 1) is alginic acid grafted with long alkyl chain quaternary ammonium salt, and the grafting ratio of long alkyl chain quaternary ammonium salt is 3%-10%.

Further, the alginic acid or alginate described in step 1) needs to be made into an aqueous solution with a mass fraction of 2-10%. After adding epichlorohydrin, N,N-dimethylxalkyl tertiary amine, the React at 70°C for 10-60 hours.

Further, the precipitate described in step 2) is a sodium alginate quaternary ammonium salt product that is agglomerated together due to electrostatic interaction.

Further, the electrolyte solution described in step 2) is sodium chloride or potassium chloride solution.

2. The product prepared according to the above-mentioned preparation method of a cationized alginic acid hemostatic material.

3. The application of the above-mentioned cationic alginic acid hemostatic material in the preparation of temperature-sensitive hemostatic gel products, the application method is as follows: the temperature-sensitive polymer is prepared into a solution with a concentration of 150-300 mg/mL, and then added with a concentration of A solution of 0.5-2 mg/mL cationized alginic acid hemostatic material forms a thermosensitive gel.

Further, the thermosensitive polymer is poloxamer, a mixture of poloxamer and hydroxypropyl methylcellulose, a mixture of poloxamer and hydroxypropyl cellulose, or a mixture of poloxamer and hydroxypropylmethylcellulose. A mixture of propylmethylcellulose and hydroxypropylcellulose.

Further, the solvent of the temperature-sensitive polymer solution is water, physiological saline, phosphate buffer saline or glucose solution, and the solvent of the solution of the cationized alginic acid hemostatic material is consistent with the solvent of the temperature-sensitive polymer solution.

The beneficial effects of the present invention are: the present invention provides a preparation method of cationic alginic acid hemostatic material, in the molar ratio of epichlorohydrin to N,N-dimethyl x alkyl tertiary amine (x=10～14) One-pot reaction with alginic acid or alginate in aqueous solution under the condition of 10:11～10:13, the following process will occur:

1) Between epichlorohydrin and N,N-dimethyl x alkyl tertiary amine (x = 10 ~ 14), the substitution reaction of haloalkane to tertiary amine is easy to generate a long alkyl quaternary ammonium salt with epoxy group ;

2) In the above two reaction systems, N,N-dimethyl x alkyl tertiary amines with a molar excess of 0.1-0.3 times can capture hydrogen ions in water to form ligands through tertiary amines, which will make the aqueous solution weakly alkaline, Then catalyze the reaction of hydroxyl and carboxyl groups in alginic acid or alginate with epoxy groups, and realize the grafting of long alkyl quaternary ammonium salts with epoxy groups onto alginic acid;

3) Thereafter, electrostatic assembly of the two will It leads to the formation of water-insoluble precipitates in the system. The two-step reaction between the precipitates and the aforementioned 1) and 2) can still be carried out, and may even be accelerated due to high local concentrations (of course, there are also negative effects of increased steric hindrance) , and more importantly, the appearance of this precipitate also realizes the rapid separation of the cationized alginic acid product from the aqueous solution, which greatly reduces the use of precipitating agents. In the subsequent post-treatment process of the product, use electrolytes such as sodium chloride to post-treat the obtained precipitates and disassemble the electrostatic assembly, which can further accelerate the removal of unreacted raw materials, reduce the use of precipitants, and increase productivity.

For the application of hemostasis, this preparation method is by limiting epichlorohydrin (the feeding molar ratio of alginic acid or alginate to epichlorohydrin is 1:0.5～1:1.5) and N,N-dimethyl x alkyl tertiary The feeding range of amine (the molar ratio of epichlorohydrin to N,N-dimethyl x alkyl tertiary amine is 10:11~10:13) has less grafting on sodium alginate High rate of long alkyl chain quaternary ammonium salts, so that the prepared cationized alginic acid material maintains good blood compatibility while having good procoagulant properties, (the procoagulant properties come from the promotion of blood by a small amount of long alkyl quaternary The components are aggregated, and the existence of a large number of carboxyl groups avoids the interference of the overly positive charge on the coagulation factor), which will be more widely used in the field of medical hemostatic products. Finally, the preparation and application of a temperature-sensitive hemostatic gel was demonstrated by mixing the temperature-sensitive polymer solution with cationized alginic acid. polymer solution).

Description of drawings

In order to make the purpose, technical scheme and beneficial effect of the present invention clearer, the present invention provides the following drawings:

Fig. 1 The photo of a large amount of foam produced by the precipitate obtained after the stirring reaction of 50% sodium chloride solution

Figure 2 The product after fully foaming is precipitated with absolute ethanol to obtain a photo of a fine granular product that is easy to wash

Figure 3 is the photo of granular cationized alginic acid obtained after washing

Figure 4 The photo of the foam produced by the precipitate obtained after the stirring reaction of 10% sodium chloride solution

Detailed ways

Preferred embodiments of the present invention are described in detail below.

Example 1

1) Take 4g of sodium alginate (viscosity of 1000mPa·s), add it to 80mL of deionized water, then add 1mL of epichlorohydrin, 3.2mL of N,N-dimethyldecylamine, in the atmosphere of _N2 , and reacted at 40°C for 24h.

2) the precipitate obtained by the reaction is stirred with 50% sodium chloride solution after the reaction, and after a large amount of foam (this process is called foaming) is produced in the system because of stirring (Fig. 1), it is washed three times with dehydrated alcohol (including Precipitation, stirring and centrifugation (as shown in Fig. 2 and Fig. 3 ), each time for 2 hours, were vacuum-dried to obtain cationized alginic acid X1 with a grafting rate of 4%.

In this example, the molar ratio SA (sodium alginate):EP (epichlorohydrin):NH ₂ (tertiary amine on N,N-dimethyldecylamine)=1:0.619:0.681, N,N-di The number of carbon atoms on methyldecylamine is 10.

As can be seen from Fig. 1, stirring in 50% sodium chloride solution, the precipitate obtained after the completion of the reaction can produce a large amount of fine and dense foam.

It can be seen from Figure 2 that using absolute ethanol for precipitation, the product obtained after foaming can be evenly dispersed in the ethanol solution, which facilitates the removal of unreacted raw materials during the washing process.

It can be seen from Figure 3 that the product obtained after washing is in a relatively dispersed state, which proves that it has been fully washed.

Example 2

1) Take 4g of sodium alginate (with a viscosity of 1000mPa·s), add it to 80mL of deionized water, then add 1mL of epichlorohydrin, 3.2g of N,N-dimethyldodecylamine, and add it under N ₂ The atmosphere was reacted at 40°C for 24h.

2) After the reaction is completed, stir the precipitate obtained by stirring the reaction with 50% sodium chloride solution. After a large amount of foam is generated in the system due to stirring, wash with absolute ethanol precipitation three times, each time for 2 hours, and then vacuum-dry to obtain the graft 5% cationic alginic acid X2.

In this example, the molar ratio SA (sodium alginate): EP (epichlorohydrin): NH ₂ (tertiary amine on N,N-dimethyldodecylamine)=1:0.619:0.681, N, The number of carbon atoms in N-dimethyldodecylamine is 12.

Example 3

Poloxamer (F127) was formulated into a solution with a concentration of 200 mg/mL with physiological saline, and the cationized alginic acid X1 in Example 1 was added so that its concentration in the solution was 1 mg/mL to obtain a poloxamer with hemostatic properties Gel X3.

Example 4

Poloxamer (F127) was formulated into a solution with a concentration of 240 mg/mL with physiological saline, and the cationized alginic acid X2 in Example 2 was added so that its concentration in the solution was 1 mg/mL to obtain a poloxamer with hemostatic properties Gel X4.

Comparative example 1

1) Take 4g of sodium alginate (viscosity of 1000mPa s), add it to 80mL of deionized water, then add 1mL of epichlorohydrin, 3.2mL of N,N-dimethylbutylamine, in the atmosphere of _N2 , and reacted at 40°C for 24h.

2) After the reaction is completed, the reaction system is a homogeneous system, no precipitate can be obtained, and the cationized alginic acid cannot be separated efficiently.

In this scheme, there are only 4 carbons in the carbon chain of N,N-dimethylbutylamine, and its hydrophobicity is lower than that of tertiary amines with 10 carbons, and because of its shorter carbon chain, there is less entanglement with alginate , so the electrostatic assembly between the positively charged tertiary amine and the negatively charged cationic alginic acid is greatly weakened, so that no precipitate can be formed in the system, and the product cannot be obtained.

Comparative example 2

1) Take 4g of sodium alginate (viscosity of 1000mPa s), add it to 80mL of deionized water, then add 4mL of epichlorohydrin, 12.8mL of N,N-dimethyldecylamine, and add it in the atmosphere of _N2 , and reacted at 40°C for 24h.

2) Stir the precipitate obtained with 50% sodium chloride solution at the end of the reaction to untie the entanglement of molecular chains. After vigorous foaming, wash with absolute ethanol precipitation three times, each time for 2 hours, and then vacuum-dry to obtain the graft Cationic alginic acid Y2 in an amount of 15%.

In this scheme, the feeding molar ratio of alginic acid or alginate and epichlorohydrin is 1: 2.5, outside the scope of 1: 0.5～1: 1.5 claimed in claim 1, the product obtained hemolysis (hemolysis rate up to 30.2%, see Table 1).

Comparative example 3

1) Take 4g of sodium alginate (with a viscosity of 1000mPa·s), add it to 80mL of deionized water, then add 0.5mL _of epichlorohydrin, 1.6mL of N,N-dimethyldecylamine, In the reaction at 40°C for 24h.

2) After the reaction, although there were certain precipitates, the yield of isolated cationized alginic acid was extremely low, about 2%, which could not support subsequent experiments.

In this scheme, the molar ratio of alginic acid to epichlorohydrin is 1:0.31 (outside the range of 1:0.5～1:1.5 claimed in claim 1), epichlorohydrin and N,N-dimethyl The molar ratio of decylamine is maintained at 10:11, so, compared with epichlorohydrin, although a slight excess of N,N-dimethyldecylamine provides a weakly alkaline environment to allow the reaction to proceed, but due to the overall system Among them, the amount of epichlorohydrin and N,N-dimethyldecylamine is too low compared to alginic acid, resulting in a low degree of reaction, very little precipitate, and very low yield, which has no application value .

Comparative example 4

1) Take 4g of sodium alginate (viscosity of 1000mPa·s), add it to 80mL of deionized water, then add 1mL of epichlorohydrin, 3.2mL of N,N-dimethyldecylamine, in the atmosphere of _N2 , and reacted at 40°C for 24h.

2) After the reaction, wash the precipitated product directly with absolute ethanol, wash with absolute ethanol for three times, each time for 2 hours, and then vacuum-dry to obtain cationized alginic acid Y4.

In this scheme, the product was obtained by washing directly with absolute ethanol without stirring and foaming with sodium chloride solution, and the obtained product was hemolyzed (the hemolysis rate was as high as 33.5%, see Table 1).

Comparative example 5

1) Take 4g of sodium alginate (with a viscosity of 1000mPa·s), add it to 80mL of deionized water, then add 1mL of epichlorohydrin and 3.2mL of N,N-dimethyldecylamine, and in an atmosphere of N2, React at 40°C for 24h.

2) The precipitate obtained by stirring with 10% sodium chloride solution at the end of the reaction has a small amount of foam in the system, which is precipitated and washed three times with absolute ethanol, each time for 2 hours, and then vacuum-dried to obtain a grafted amount of 4%. Cationized alginic acid Y5.

In this scheme, the product is stirred with a low-concentration sodium chloride solution, and the molecular chain entanglement is not completely untied, which is not conducive to the removal of residual quaternary ammonium salts, and the obtained product is hemolyzed (the hemolysis rate is as high as 25.3%, see Table 1).

As can be seen from Fig. 4, 10% sodium chloride solution stirs and obtains a small amount of foam, and this is because the concentration of sodium chloride solution is low, cannot obtain the product of sufficient foaming, is unfavorable for the washing of product.

Comparative example 6

1) Take 4g of sodium alginate (viscosity of 1000mPa s), add it to 80mL of deionized water, then add 1mL of epichlorohydrin, 1.4mL of N,N-dimethyldecylamine, in the atmosphere of _N2 , and reacted at 40°C for 24h.

2) After the reaction, very few precipitates were obtained, and the yield of isolated cationized alginic acid was extremely low, which could not support subsequent experiments.

In this scheme, the molar ratio of epichlorohydrin to N,N-dimethyldecylamine is 10:5, which is less than the 10:11～10:13 claimed in claim 1, N,N-dimethyldecylamine The amount is too small to provide a weak alkaline environment, which is not conducive to catalyzing the reaction of hydroxyl and carboxyl groups in alginic acid or alginate with epoxy groups, resulting in a reduction in the reaction efficiency of long alkyl quaternary ammonium salts grafted to alginic acid. The yield is extremely low and does not have application value.

Comparative example 7

Poloxamer (F127) was prepared into a solution with a concentration of 200 mg/mL with physiological saline, and sodium alginate (viscosity of 1000 mPa·s) was added to make its concentration in the solution 1.5 mg/mL to obtain gel Y7.

In this protocol, only ordinary sodium alginate (not modified with cationization) was added.

Comparative example 8

Poloxamer (F127) was formulated into a solution with a concentration of 200 mg/mL with physiological saline, and the cationized alginic acid X1 in Example 1 was added so that its concentration in the solution was 0.1 mg/mL to obtain gel Y8 .

In this scheme, the concentration of cationized alginic acid X1 is less than the range of 0.5-2 mg/mL.

Comparative example 9

Poloxamer (F127) was formulated into a solution with a concentration of 200 mg/mL with physiological saline, and the cationized alginic acid X1 in Example 1 was added to make its concentration in the solution 5 mg/mL to obtain gel Y9.

In this solution, the concentration of cationized alginic acid X1 is greater than 0.5-2 mg/mL.

Comparative example 10

Poloxamer (F127) was formulated into a solution with a concentration of 200 mg/mL with physiological saline to obtain gel Y10.

The program only has poloxamer, without adding any other modified materials.

Test Example 1 Blood Compatibility Test

Test conditions: Examples 1, 2, 3, 4, Comparative Examples 2, 4 and sodium alginate raw material (viscosity 1000mPa·s) were tested for blood compatibility. Detection method: hemolysis rate test, the blood used for detection is fresh SD rat sodium citrate anticoagulant blood, and the test material is prepared as a 1 mg/mL solution with physiological saline. Whole blood was centrifuged (3000 rpm, 10 min), and blood cells were collected, washed twice with normal saline, and then prepared into a 4% solution with normal saline. Equal volumes of the test material solution and the blood cell solution were mixed (each 250 uL), the final concentration was 2% of blood cells, and the test material was 1 mg/mL. And set positive and negative control group, negative control group is the normal saline solution (250uL) of equal volume with blood cell solution, positive control group is the 4% triton solution (250uL) of equal volume with blood cell solution. Incubate at 37°C for 3 hours, centrifuge (3000rpm, 3min), take 100uL of the supernatant and add it to a 96-well plate, and read the absorbance Abs of each well at 545nm with a microplate reader. Finally, the hemolysis rate was calculated by the following formula.

Hemolysis rate=(Abs material-Abs negative)/(Abs positive-Abs negative)×100%...................Formula

In the formula: Abs material is the absorbance of the material group at 545nm; Abs positive is the absorbance of the positive group at 545nm; Abs negative is the absorbance of the negative group at 545nm. The hemolysis rate of embodiment and comparative example is as follows:

Table 1 Hemolysis rate test

Table 1 Hemolysis rate test

sample X1 X2 X3 X4 Y2 Y4 Y5 sodium alginate Hemolysis rate (%) 1.5 1.2 0.9 1.2 30.2 33.5 25.3 0.6

The hemolysis rate is used to characterize the erythrocyte compatibility of blood-contact materials. Hemolysis means that after the blood contacts with the material, the erythrocytes are broken in large quantities and a large amount of hemoglobin is released. Generally speaking, when the hemolysis rate is less than 5%, it means that the blood compatibility of the material is better; when the hemolysis rate is greater than 5%, it means that the material has certain toxicity, causing more red blood cells to rupture, which will damage the composition and composition of blood. Function, should not be used as blood contact material (the country stipulates that the hemolysis rate of any blood contact material should not exceed 5%), which limits its application in the field of hemostasis.

It can be seen from Table 1 that the hemolysis rates of X1, X2, X3 and sodium alginate are all lower than 5%. The cationized alginic acid (X1, X2) of quaternary ammonium salts and the gels (X3, X4) prepared on this basis can also continue to maintain good blood compatibility. And in the process of preparing X1 and X2 systems, the use of electrolyte solution during post-treatment weakens the positive and negative attraction between the negatively charged carboxyl groups of sodium alginate and tertiary amines and quaternary ammonium salts, so that in the process of washing, the ungrafted /Residual quaternary ammonium salt and tertiary amine impurities can be removed to the greatest extent, which is beneficial to the removal of quaternary ammonium salt, with low hemolysis rate and good blood compatibility.

The hemolysis rate of the comparative example Y2 is as high as 30.2%, indicating that the material is very toxic, because the reaction system for preparing the anti-material uses excess epichlorohydrin and excess N,N-dimethyldecylamine, resulting in the final There are too many quaternary ammonium salts grafted on the cationized alginic acid. Due to the toxicity of excessive quaternary ammonium salts, the cell membrane of red blood cells will be ruptured, resulting in increased hemolysis rate and poor blood compatibility.

The hemolysis rate of the comparative example Y4 is as high as 33.55%, indicating that the material is very toxic. The reason is that no sodium chloride was added during the post-treatment of the reaction, and the precipitate was washed directly. The positive and negative attraction of quaternary ammonium salts makes it difficult to effectively remove ungrafted/residual quaternary ammonium salts and tertiary amine impurities, which is not conducive to the removal of quaternary ammonium salt residues, resulting in increased hemolysis rate and poor blood compatibility.

The hemolysis rate of comparative example Y5 is also higher and is 25.3%, illustrates that the biotoxicity of material is very big, and reason is although adding sodium chloride solution dissociation during the aftertreatment of reaction, but the concentration of added sodium chloride solution is too low, The dissociation of the precipitated matter is not complete, so that the molecular chain entanglement is not completely opened, which is not conducive to the subsequent washing, so that the ungrafted/residual quaternary ammonium salt and tertiary amine impurities in the system are not completely removed, resulting in an increase in the hemolysis rate. Blood compatibility is not good.

Test example 2 Comparison of coagulation effect in vitro

Testing conditions: Example 1, 2, 4 and comparative examples 7, 8, 9, 10 and sodium alginate raw material (viscosity 1000mPa·s) were tested for coagulation effect in vitro. Test method: Put test samples (50 μL for gel, 5 mg for powder) into 2 mL plastic centrifuge tubes, and incubate in a constant temperature water bath at 37 °C for 5 minutes; then take 100 μL of fresh anticoagulated blood and 10 μL of calcium chloride solution (CaCl ₂ ; 0.2M) and mix well to form about 100 μL of recoagulated blood; add the recoagulated blood to the surface of the sample and incubate in a constant temperature water bath at 37°C for 1 minute. Finally, add 10 mL of deionized water to fully lyse the excess blood that has not formed a blood clot, and continue to incubate for 3 minutes to release hemoglobin (HGB); absorb 2 mL of the lysed liquid and centrifuge (2500rmp, 3 minutes), and take 100 μL The centrifuged supernatant was added to a 96-well plate, and the absorbance at 545 nm was measured by an enzyme-linked immunosorbent assay instrument to calculate the hemoglobin content. In the blank group, 100 μL of fresh anticoagulated blood was directly added to 10 mL of deionized water, incubated in a constant temperature water bath at 37°C for 3 minutes, and 100 μL was drawn to test the absorbance Abs at 545 nm. Finally, the coagulation index (BCI) was calculated by the following formula.

Coagulation index % (BCI) = (Abs material / Abs blank) × 100% ................... Formula

In the formula: Abs material is the absorbance of the material group at 545nm; Abs blank is the absorbance of the blank group at 545nm. The BCI index of embodiment and comparative example is as follows:

Table 2 In vitro blood coagulation effect test

BCI (Blood clotting index, coagulation index) can characterize the coagulation effect of the material, and generally the smaller the value of BCI, the better the coagulation effect of the material. It can be seen from Table 2:

The BCI indexes of the hemostatic materials X1-X4 obtained in Examples 1, 2, 3, and 4 of the present invention are significantly lower than those of Comparative Examples 7, 8, 9, and 10 and sodium alginate. It can be seen that after the sodium alginate is modified by the preparation method of the present invention, a small amount of quaternary ammonium salt is grafted in a certain proportion. Glue (a certain concentration of cationized sodium alginate is added to the temperature-sensitive polymer solution, namely X3, X4), can obtain a hemostatic material with excellent hemostatic performance.

The hemostatic performance of sodium alginate powder is also lower than that of the corresponding examples X1 and X2; Y7 is a gel added with unmodified alginic acid, and its hemostatic performance is lower than that of the corresponding examples X3 and X4; this difference in performance effectively illustrates the Chemical modification improves the hemostatic effect of alginic acid. In addition, the in vitro blood coagulation performance of comparative examples Y8, Y9, and Y10 is not good, because the gel preparation method is not suitable, specifically:

1) The reason for the poor coagulation performance of Y8 in vitro is that the concentration of cationic sodium alginate with hemostatic properties in the gel system is too low, only 0.1 mg/mL, which does not effectively improve the coagulation effect of the gel.

2) The reason for the poor coagulation performance of Y9 in vitro is that the concentration of cationized sodium alginate with hemostatic properties in the gel system is too high, which is 5 mg/mL, and the excessively high content of cationized sodium alginate will cause blood coagulation when it contacts with blood. Inhibiting the activity of coagulation-related factors is also not conducive to the coagulation effect.

3) Y10 is a gel prepared by using poloxamer (F127) alone without adding any modified materials. The BCI results show that the hemostatic performance of the gel is not as good as that after adding cationized alginic acid. Therefore, cationized sodium alginate can improve the hemostatic performance of the gel.

Finally, it should be noted that the above preferred embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail through the above preferred embodiments, those skilled in the art should understand that it can be described in terms of form and Various changes may be made in the details without departing from the scope of the invention defined by the claims.

Claims (9)

1. A preparation method for a cationic alginic acid hemostatic material, characterized in that the preparation steps are: 1) One-pot reaction of alginic acid or alginate with epichlorohydrin, N,N-dimethyl x alkyl tertiary amine, said x=10～14, the reaction of said one-pot reaction The temperature is 30-70°C, and the reaction time is 10-60 hours; the molar ratio of epichlorohydrin to N,N-dimethylxyl tertiary amine is 10:11-10:13; the The molar ratio of alginic acid or alginate to epichlorohydrin is 1:0.5～1:1.5; 2) After the reaction is over, stir the precipitate obtained by the reaction with an electrolyte solution with a concentration of 50% to 80%, untie the entanglement of molecular chains, and obtain a foamed product, precipitate and wash with absolute ethanol to obtain cationized seaweed Acid hemostatic material. 2. the preparation method of a kind of cationic alginic acid hemostatic material according to claim 1, is characterized in that, the product obtained in step 1) is alginic acid grafted long alkyl chain quaternary ammonium salt, long alkyl chain quaternary ammonium salt The grafting rate of salt is 3%-10%. 3. A method for preparing a cationized alginic acid hemostatic material according to claim 1, characterized in that the alginic acid or alginate in step 1) needs to be made into an aqueous solution with a mass fraction of 2-10%, After adding epichlorohydrin and N,N-dimethyl x alkyl tertiary amine, react at 30-70°C for 10-60 hours. 4. The preparation method of a cationic alginic acid hemostatic material according to claim 1, characterized in that, the precipitate described in step 2) is a sodium alginate quaternary ammonium salt product that is agglomerated together due to electrostatic interaction. 5. The preparation method of a cationic alginic acid hemostatic material according to claim 1, characterized in that the electrolyte solution in step 2) is sodium chloride or potassium chloride solution. 6. The product prepared according to the preparation method of a cationic alginic acid hemostatic material according to any one of claims 1-5. 7. The application of a cationized alginic acid hemostatic material according to claim 6 in the preparation of temperature-sensitive hemostatic gel products, characterized in that the application method is as follows: the temperature-sensitive polymer is configured to a concentration of 150-300 mg /mL solution, and then add a solution of cationized alginic acid hemostatic material with a concentration of 0.5-2 mg/mL to form a thermosensitive gel. 8. The application of a cationized alginic acid hemostatic material according to claim 7 in the preparation of temperature-sensitive hemostatic gel products, characterized in that, the temperature-sensitive polymer is poloxamer, poloxamer A mixture of shamers and hydroxypropylmethylcellulose, a mixture of poloxamers and hydroxypropylcellulose, or a mixture of poloxamers with hydroxypropylmethylcellulose and hydroxypropylcellulose. 9. The application of a cationized alginic acid hemostatic material according to claim 7 in the preparation of temperature-sensitive hemostatic gel products, wherein the solvent of the temperature-sensitive polymer solution is water, normal saline, Phosphate buffer saline or glucose solution, the solvent of the solution of the cationized alginic acid hemostatic material is consistent with the solvent of the thermosensitive polymer solution.