A self-gelling polysaccharide hemostatic powder and a preparation method and application thereof

Abstract

The application provides a self-gel polysaccharide hemostatic powder and a preparation method and application thereof, and belongs to the medical field. The self-gel polysaccharide hemostatic powder is prepared based on natural polysaccharides through chemical modification, and can realize rapid self-gel. The hemostatic powder has good hydrophilicity and liquid absorption capacity, can realize powder-gel transformation, and forms a stable physical barrier. The hemostatic powder has a wide application prospect in the preparation of hemostatic materials.

Description

Technical Field

[0001] This invention belongs to the field of medicine, specifically relating to a self-gelling polysaccharide hemostatic powder, its preparation method, and its application. Background Technology

[0002] Acute trauma is common in military training and daily life, and uncontrollable bleeding and wound infection following tissue damage are major causes of injury and death. Therefore, effective hemostasis in emergency care is crucial for improving patient survival rates. Powdered materials, with their large specific surface area and excellent liquid absorption capacity, can concentrate coagulation-related substances in the blood and promote clot formation, making them an ideal choice for hemostatic materials. Self-gelling hemostatic powders can transform into hydrogels after absorbing liquid, thereby sealing the bleeding site, which also solves the problem of traditional hemostatic powders being easily washed away by blood flow.

[0003] Chitosan, an FDA-approved natural polysaccharide, has attracted considerable attention due to its low cost, excellent tissue compatibility, biodegradability, and particularly its inherent hemostatic and antibacterial properties. Carboxymethyl chitosan, a carboxymethylated derivative of chitosan, significantly improves solubility while retaining the bioactivity of chitosan. Alginate, a class of polysaccharides extracted from algae, is low in cost and safe, and has been widely used in the food industry, pharmaceuticals, and tissue repair. Therefore, carboxymethyl chitosan and alginate are ideal materials for preparing tissue adhesives. Tannic acid, a polyphenol extracted from the traditional Chinese medicine gallnut, possesses unique bioactivities such as hemostasis, anti-inflammation, antibacterial, and antioxidant properties, and has received increasing attention in the biomedical field in recent years.

[0004] Therefore, this study, based on the aforementioned natural polysaccharides, prepared a polysaccharide hemostatic powder capable of rapid self-gelation through chemical modification. The hemostatic powder exhibits good hydrophilicity and liquid absorption capacity, enabling a powder-to-gel transition and the formation of a stable physical barrier. Summary of the Invention

[0005] The purpose of this invention is to provide a self-gelling polysaccharide hemostatic powder, its preparation method, and its application.

[0006] This invention provides a self-gelling polysaccharide hemostatic material, which is prepared from the following raw materials in parts by weight: 1-15 parts of borate ester graft-modified oxidized alginate and 1-15 parts of dopamine-modified polysaccharide.

[0007] Furthermore, it is prepared from the following raw materials in parts by weight: 6-10 parts of borate ester graft modified oxidized alginate and 6-10 parts of dopamine modified polysaccharide.

[0008] Furthermore, the self-gelling polysaccharide hemostatic material is a self-gelling polysaccharide hemostatic hydrogel material or a self-gelling polysaccharide hemostatic powder material.

[0009] Furthermore, the boronic acid ester graft-modified oxidized alginate is 3-aminophenylboronic acid graft-modified oxidized alginate, preferably sodium oxidized alginate; the dopamine-modified polysaccharide is a polysaccharide modified with L-DOPA, preferably carboxymethyl chitosan.

[0010] Furthermore, the method for synthesizing the borate ester bond grafted modified oxidized alginate includes the following steps:

[0011] (1) Dissolve alginate and oxidant in a solvent, and oxidize alginate after reaction;

[0012] (2) Dissolve oxidized alginate and activator in a solvent, add 3-aminophenylboronic acid solution, and after the reaction, boronic acid ester bond graft modified oxidized alginate is obtained.

[0013] Further, in step (1), the oxidant is sodium periodate; the mass ratio of alginate to oxidant is 1:0.1-0.5; the solvent for the reaction is an organic solvent; the reaction temperature is 10-40℃ and the time is 4-8 hours;

[0014] In step (2), the activator is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride; the solvent for the reaction is an inorganic solvent; the molar ratio of the oxidized alginate, the activator and 3-aminophenylboronic acid is 1:1-5:1-3; the solvent in the 3-aminophenylboronic acid solution is an organic solvent; the reaction temperature is 10-40℃ and the time is 20-30 hours.

[0015] Furthermore, the method for synthesizing the dopamine-modified polysaccharide includes the following steps:

[0016] (i) Carboxymethyl chitosan, methacrylic anhydride and base are reacted to obtain methacrylic anhydride modified carboxymethyl chitosan;

[0017] (ii) Reacting methacrylic anhydride-modified carboxymethyl chitosan, levodopa, and an activator to produce a dopamine-modified polysaccharide.

[0018] Further, in step (i), the alkali is sodium hydroxide; the mass ratio of carboxymethyl chitosan to methacrylic anhydride is 1:2-4; the reaction temperature is 0-8°C, and the time is 10-20 min;

[0019] In step (ii), the activator is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide; the molar ratio of the methacrylic anhydride-modified carboxymethyl chitosan, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide, and levodopa is 1:1-2:1-2:1-3; the reaction temperature is 10-40°C, and the time is 20-30 hours.

[0020] The present invention also provides a method for preparing the above-mentioned self-gelling polysaccharide hemostatic material, the method comprising the following steps: mixing a borate ester bond graft-modified oxidized alginate solution and a dopamine-modified polysaccharide solution, adjusting the pH to form a self-gelling polysaccharide hemostatic hydrogel material; or, the method further comprising the following steps: freeze-drying and grinding the hydrogel to obtain a self-gelling polysaccharide hemostatic powder material.

[0021] The present invention also provides the use of the above-mentioned self-gelling polysaccharide hemostatic material in the preparation of hemostatic materials.

[0022] The present invention has achieved the following beneficial effects:

[0023] This invention, based on natural polysaccharides, utilizes chemical modification to prepare a polysaccharide hemostatic powder capable of rapid self-gelation. This hemostatic powder exhibits excellent hydrophilicity and liquid absorption capacity, enabling a powder-to-gel transition and the formation of a stable physical barrier. It shows broad application prospects in the preparation of hemostatic materials.

[0024] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0025] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following embodiments. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0026] Figure 1 The preparation process of (a) modified sodium alginate and (b) modified carboxymethyl chitosan is described.

[0027] Figure 2 This refers to the self-gelation process of polysaccharide hemostatic powder. Detailed Implementation

[0028] The raw materials and equipment used in this invention are all known products, obtained by purchasing commercially available products.

[0029] The "room temperature" condition referred to in this invention is 25±5℃.

[0030] Example 1: Preparation of self-gelling polysaccharide hemostatic powder

[0031] 1. Synthesis of modified sodium alginate

[0032] Synthesis of modified sodium alginate, such as Figure 1 As shown in a:

[0033] (1) Disperse sodium alginate in anhydrous ethanol at a ratio of 2% (unit g / mL) and stir continuously. Dissolve NaIO4 in water of the same volume as anhydrous ethanol (the mass of NaIO4 is 0.25 times that of sodium alginate).

[0034] (2) Under light-protected conditions, NaIO4 solution was added dropwise to the sodium alginate / anhydrous ethanol dispersion system, and the reaction was carried out at room temperature for 6 hours. After the reaction was completed, 15 mL of ethylene glycol was added and stirred for 30 minutes to terminate the reaction.

[0035] (3) The reaction product was placed in a dialysis bag (molecular weight cutoff of 3500 Da) and dialyzed in deionized water for 3 days, changing the water 3 times a day. The aldehyde-modified sodium alginate (ADA) sample was obtained by freeze drying.

[0036] (4) Dissolve ADA completely in water at a concentration of 0.5% (g / mL), and add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and stir until completely dissolved.

[0037] (5) Dissolve 3-aminophenylboronic acid (PBA) in anhydrous ethanol and add it dropwise to ADA solution. Adjust the pH to 7 and react for 24 hours. The molar ratio of ADA, PBA and EDC is 1:2:3.

[0038] (6) After the reaction is complete, the ADA-PBA sample is obtained by dialysis and freeze-drying.

[0039] 2. Synthesis of modified carboxymethyl chitosan

[0040] Synthesis of modified carboxymethyl chitosan, such as Figure 1 As shown in b:

[0041] (1) Dissolve carboxymethyl chitosan (CMCS) in pure water at a ratio of 2% (unit g / mL) at room temperature and incubate it in a water bath at 4℃ for 15 min.

[0042] (2) Add methacrylic anhydride (MA) dropwise. The mass-volume ratio of CMCS to MA is 1:3. Adjust the pH of the system to 9 with 5% NaOH and continue the reaction at 4°C for 24 hours.

[0043] (3) After the reaction was completed, the reaction product was placed in a dialysis bag (molecular weight cutoff of 3500 Da) and dialyzed in deionized water for 3 days, changing the water 3 times a day. After dialysis, the CMCS-MA sample was obtained by freeze drying.

[0044] (4) Dissolve CMCS-MA completely in water at a concentration of 0.5% (unit g / mL), and add EDC and N-hydroxysuccinimide (NHS) under nitrogen atmosphere. The amount of EDC and NHS is 1.5 times that of CMCS-MA.

[0045] (5) Add levodopa (DOPA) solution (DOPA dissolved in 1M HCl) to the solution in step (4), and react at room temperature in the dark for 24 hours under conditions of pH=5.5. The molar ratio of CMCS-MA to DOPA is 1:2. The entire reaction is carried out in a nitrogen atmosphere.

[0046] (6) After the reaction is complete, the CMCS-MAD sample is obtained by dialysis and freeze drying.

[0047] 3. Preparation of polysaccharide hemostatic powder

[0048] (1) The lyophilized ADA-PBA was dissolved at a mass-volume ratio (g / mL) of 8% in 0.02% NaOH PBS solution containing 1% LAP (phenyl-2,4,6-trimethylbenzoyl lithium phosphinate, photoinitiator). The solution was incubated at 50°C for 15 min to ensure complete dissolution and was ready for use.

[0049] (2) Dissolve the lyophilized CMCS-MAD in PBS solution at a mass-volume ratio of 8% (g / mL). Incubate at 50°C for 15 min to ensure complete dissolution, and set aside for later use.

[0050] (3) Mix the solutions from steps (1) and (2) at a volume ratio of 1:1, adjust the pH of the system to between 7 and 8 with 2% NaOH PBS solution to form a gel. After further freeze-drying, prepare the polysaccharide hemostatic powder using a physical grinding method.

[0051] (4) After application, this hemostatic powder can absorb water and transform into a gel state. Based on this, it can be irradiated with 405nm blue light to form a gel system with better mechanical and adhesive properties. Figure 2 ).

[0052] In summary, this invention provides a self-gelling polysaccharide hemostatic powder, its preparation method, and its applications. Based on natural polysaccharides, this invention, through chemical modification, prepares a polysaccharide hemostatic powder that can rapidly achieve self-gelation. This hemostatic powder exhibits good hydrophilicity and liquid absorption capacity, enabling a powder-to-gel transition and forming a stable physical barrier. It has broad application prospects in the preparation of hemostatic materials.

Claims

1. A self-gelling polysaccharide hemostatic material, characterized in that, It is prepared from the following raw materials in parts by weight: 1-15 parts of borate ester graft modified oxidized alginate and 1-15 parts of dopamine modified polysaccharide.

2. The self-gelling polysaccharide hemostatic material according to claim 1, characterized in that, It is prepared from the following raw materials in parts by weight: 6-10 parts of borate ester graft modified oxidized alginate and 6-10 parts of dopamine modified polysaccharide.

3. The self-gelling polysaccharide hemostatic material according to claim 1, characterized in that, The self-gelling polysaccharide hemostatic material is a self-gelling polysaccharide hemostatic hydrogel material or a self-gelling polysaccharide hemostatic powder material.

4. The self-gelling polysaccharide hemostatic material according to any one of claims 1-3, characterized in that, The boronic acid ester graft-modified oxidized alginate is 3-aminophenylboronic acid graft-modified oxidized alginate, preferably sodium oxidized alginate; the dopamine-modified polysaccharide is a polysaccharide modified with L-DOPA, preferably carboxymethyl chitosan.

5. The self-gelling polysaccharide hemostatic material according to claim 4, characterized in that, The method for synthesizing the borate ester graft modified oxidized alginate includes the following steps: (1) Dissolve alginate and oxidant in a solvent, and oxidize alginate after reaction; (2) Dissolve oxidized alginate and activator in a solvent, add 3-aminophenylboronic acid solution, and after the reaction, boronic acid ester bond graft modified oxidized alginate is obtained.

6. The self-gelling polysaccharide hemostatic material according to claim 5, characterized in that, In step (1), the oxidant is sodium periodate; the mass ratio of alginate to oxidant is 1:0.1-0.5; the solvent for the reaction is an organic solvent; the reaction temperature is 10-40℃ and the reaction time is 4-8 hours. In step (2), the activator is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride; the solvent for the reaction is an inorganic solvent; the molar ratio of the oxidized alginate, the activator and 3-aminophenylboronic acid is 1:1-5:1-3; the solvent in the 3-aminophenylboronic acid solution is an organic solvent; the reaction temperature is 10-40℃ and the time is 20-30 hours.

7. The self-gelling polysaccharide hemostatic material according to claim 4, characterized in that, The method for synthesizing the dopamine-modified polysaccharide includes the following steps: (i) Carboxymethyl chitosan, methacrylic anhydride and base are reacted to obtain methacrylic anhydride modified carboxymethyl chitosan; (ii) Reacting methacrylic anhydride-modified carboxymethyl chitosan, levodopa, and an activator to produce a dopamine-modified polysaccharide.

8. The self-gelling polysaccharide hemostatic material according to claim 7, characterized in that, In step (i), the alkali is sodium hydroxide; the mass ratio of carboxymethyl chitosan to methacrylic anhydride is 1:2-4; the reaction temperature is 0-8°C and the time is 10-20 min. In step (ii), the activator is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide; the molar ratio of the methacrylic anhydride-modified carboxymethyl chitosan, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide, and levodopa is 1:1-2:1-2:1-3; the reaction temperature is 10-40°C, and the time is 20-30 hours.

9. A method for preparing the self-gelling polysaccharide hemostatic material according to any one of claims 1-8, characterized in that, The method includes the following steps: mixing a borate ester bond graft-modified oxidized alginate solution and a dopamine-modified polysaccharide solution, adjusting the pH, and forming a self-gelling polysaccharide hemostatic hydrogel material; or, the method further includes the following steps: freeze-drying and grinding the hydrogel to obtain a self-gelling polysaccharide hemostatic powder material.

10. Use of the self-gelling polysaccharide hemostatic material according to any one of claims 1-8 in the preparation of hemostatic materials.

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