Polysaccharide aggregate composite hemostatic gauze and preparation method thereof

Abstract

The invention discloses polysaccharide aggregate composite hemostatic gauze and a preparation method thereof, and relates to the field of biomedical materials.The polysaccharide aggregate composite hemostatic gauze is prepared by compounding polysaccharide aggregate on the surface of gauze, adding hydrophobic molecules and an activating agent into a water-soluble polysaccharide solution, and preparing the polysaccharide aggregate composite hemostatic gauze. The preparation method comprises the following steps: grafting a hydrophobic functional substance on a polysaccharide macromolecular main chain to prepare a polysaccharide assembly modified with hydrophobic molecules; adding adhesive molecules capable of mediating supramolecular acting force and an activating agent into the polysaccharide assembly solution, and modifying the adhesive molecules and the activating agent on the polysaccharide assembly to prepare a polysaccharide aggregate modified with hydrophobic and adhesive molecules; and finally, compounding the polysaccharide aggregate on the gauze in a dipping, spraying or spin-coating manner to obtain the polysaccharide aggregate composite hemostatic gauze. The sugar aggregate composite hemostatic gauze provided by the invention has good mechanical properties and proper blood absorption, can realize ultrafast hemostasis in a massive hemorrhage scene, and improves the survival rate of the wounded.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials, and in particular to a polysaccharide aggregate composite hemostatic gauze and its preparation method. Background Technology

[0002] Bleeding is one of the leading causes of death among trauma victims, with preventable deaths from massive hemorrhage accounting for 90.9%. Therefore, achieving rapid hemostasis after massive hemorrhage is of paramount importance for improving the survival rate and success rate of treatment for the injured.

[0003] Medical gauze is a commonly used hemostatic material. It activates the physiological coagulation pathway to form a blood clot, which is then used to seal the wound and achieve hemostasis. Gauze activates physiological coagulation through its excellent hydrophilicity and capillary effect, leading to rapid blood absorption. This allows for the rapid concentration of procoagulant factors such as thrombin. However, due to gauze's high blood absorption, this often results in excessive blood loss, making it unsuitable for emergency treatment of severe bleeding.

[0004] Agglomerates are products of liquid-liquid phase separation forces; they possess the good fluidity of liquids while also repelling other liquids to some extent. Currently, most agglomerates used for hemostasis are in the form of fluids or lyophilized powders. Fluid agglomerates are inconvenient to store and transport, and they lack the ability to absorb blood; lyophilized agglomerate powders are difficult to remove after hemostasis, leading to tissue adhesion. Furthermore, both types of agglomerates have relatively weak mechanical properties and are easily washed away by high-pressure blood flow in cases of massive hemorrhage.

[0005] Polysaccharides are macromolecules composed of many linked sugar units, exhibiting good biocompatibility and degradability. Furthermore, they can be easily modified based on the hydroxyl, amino, and carboxyl groups on the sugar units, allowing for the addition of specific functional molecules. This enables them to mediate various supramolecular interactions (such as electrostatics, hydrophobicity, and hydrogen bonding) to assemble into polysaccharide aggregates.

[0006] Therefore, based on the shortcomings of gauze and aggregates in hemostasis applications and the advantages of polysaccharides in aggregate preparation, we propose to composite polysaccharide aggregates onto the surface of gauze to prepare a polysaccharide aggregate composite gauze with good mechanical properties and appropriate blood absorption, so as to achieve ultra-fast hemostasis in the case of massive bleeding and improve the survival rate of the injured. Summary of the Invention

[0007] In view of the aforementioned shortcomings of the prior art, the technical problem to be solved by the present invention is that existing gauze has excessive blood absorption capacity, causing continuous blood loss, while simple aggregates have poor mechanical properties and can be washed away by high-pressure blood flow. The present invention aims to develop a polysaccharide aggregate composite gauze with good mechanical properties and appropriate blood absorption, in order to achieve ultra-rapid hemostasis in cases of massive bleeding and improve the survival rate of injured personnel.

[0008] To achieve the above objectives, the present invention provides a polysaccharide aggregate composite hemostatic gauze in which polysaccharide aggregates are compounded onto gauze.

[0009] The polysaccharide is one or more of chitosan, hydroxymethyl chitosan, carboxypropyl chitosan, chitosan oligosaccharide, sodium alginate, hyaluronic acid, aminohyaluronic acid, cellulose nanocrystals, hydroxymethyl cellulose, hydroxypropyl cellulose, carboxyglucan, or aminoglucan.

[0010] Another aspect of the present invention provides a method for preparing a polysaccharide aggregate composite hemostatic gauze, comprising the following steps: (1) Preparation of polysaccharide aggregates Step 1: Add hydrophobic molecules and activators to the water-soluble polysaccharide solution, and graft the hydrophobic functional substances onto the main chain of the polysaccharide macromolecule to obtain a polysaccharide assembly modified with hydrophobic molecules. Step 2: Add adhesive molecules and activators that can mediate supramolecular forces to the polysaccharide assembly solution prepared in Step 1, and modify them onto the polysaccharide assembly to obtain a polysaccharide aggregate modified with hydrophobic and adhesive molecules. (2) Preparation of polysaccharide aggregate composite hemostatic gauze Step 3: The polysaccharide aggregate solution obtained in Step 2 is brought into contact with gauze for a certain period of time by impregnation, spraying or spin coating, and finally the polysaccharide aggregate composite hemostatic gauze is obtained by freeze drying or air drying.

[0011] Furthermore, step 1 also includes: adding hydrophobic molecules and activators to a water-soluble polysaccharide solution, grafting the hydrophobic functional substance onto the main chain of the polysaccharide macromolecule, and obtaining a polysaccharide assembly modified with hydrophobic molecules, wherein the molar ratio of hydrophobic molecules to polysaccharides is 0.1-10:1.

[0012] Furthermore, the water-soluble polysaccharide is one or more of chitosan, hydroxymethyl chitosan, carboxypropyl chitosan, chitosan oligosaccharide, sodium alginate, hyaluronic acid, aminohyaluronic acid, cellulose nanocrystals, hydroxymethyl cellulose, hydroxypropyl cellulose, carboxyglucan, or aminoglucan, and the concentration of the water-soluble polysaccharide is 0.1-100 mg / mL.

[0013] Furthermore, the hydrophobic molecule is one or more of the following: octanoic acid, dodecanoic acid, hexadecanoic acid, octanoic anhydride, dodecanoic anhydride, hexadecanoic anhydride, octylamine, dodecylamine, hexadecylamine, and octadecylamine.

[0014] Furthermore, step 2 also includes: adding adhesive molecules and activators to the polysaccharide assembly solution prepared in step 1, modifying the polysaccharide assembly to obtain a polysaccharide aggregate modified with hydrophobic and adhesive molecules, wherein the molar ratio of adhesive molecules to polysaccharides is 0.1-10:1.

[0015] Furthermore, the adhesive molecule is one or more of 3,4-dihydroxyphenylpropionic acid, 3,4,5-trihydroxybenzoic acid, 4-carboxyphenylboronic acid, dopamine hydrochloride, and 3-aminophenylboronic acid salt.

[0016] Furthermore, the concentration of the polysaccharide aggregate solution in step 3 is 0.1-1000 mg / mL.

[0017] Furthermore, the activator in steps 1 and 2 is selected from one or more of EDC, NHS, Hobt, and DCC.

[0018] Furthermore, the pH of the water-soluble polysaccharide solution in step 1 is 2.0-6.5.

[0019] Furthermore, the molar ratio of the water-soluble polysaccharide to the added hydrophobic molecule in step 1 is 0.1-10:1.

[0020] Furthermore, the molar ratio of water-soluble polysaccharide to added activator in step 1 is 0.1-10:1.

[0021] Furthermore, the reaction time in step 1 is 1-24 hours.

[0022] Furthermore, in step 2, the molar ratio of the polysaccharide assembly to the adhesive molecule is 0.1-10:1.

[0023] Furthermore, the molar ratio of the polysaccharide assembly to the activator in step 2 is 0.1-10:1.

[0024] Preferably, the gauze in step 3 is selected from one or more of the following: cotton gauze, medical gauze, degreased gauze, chemical fiber gauze, non-woven fabric, knitted gauze, woven gauze, and blended gauze.

[0025] Preferably, the drying method in step 3 is selected from one or more of air drying, oven drying, or freeze drying.

[0026] Furthermore, the concentration of the polysaccharide aggregate solution in step 3 is 0.1-1000 mg / mL.

[0027] Furthermore, in step 3, the gauze is soaked in the polysaccharide aggregate solution for 1 second to 72 hours.

[0028] Technical effect

[0029] The polysaccharide aggregates described in this invention can inhibit the absorption of blood by gauze. After the aggregates come into contact with blood, they form a barrier to prevent the gauze from absorbing blood, thereby improving the hemostatic properties of the gauze and reducing blood loss.

[0030] This invention utilizes gauze with good mechanical properties as a substrate to load agglomerates, enabling them to exist stably in the blood environment. The hydroxyl groups on the surface of the agglomerates and the gauze generate supramolecular interactions such as hydrogen bonds, thereby stably adhering to the gauze surface. The barrier formed by the agglomerates and blood can exist stably at the wound site, reducing blood loss. Detailed Implementation

[0031] The following describes several preferred embodiments of the present invention to make its technical content clearer and easier to understand. The present invention can be embodied in many different forms, and the scope of protection of the present invention is not limited to the embodiments mentioned herein.

[0032] Example 1

[0033] 100 g of hyaluronic acid was dissolved in 100 mL of hydrochloric acid with a pH of 6.5 to prepare an aqueous solution of hyaluronic acid with a concentration of 1000 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 30°C. Then, octanoic anhydride was added at a molar ratio of 1:10 to hyaluronic acid, and the reaction was carried out for 1 hour. The solution was then cooled to room temperature to obtain a hyaluronic acid assembly solution. Nitrogen gas was purged into a 50 mg / mL hyaluronic acid assembly solution, followed by the sequential addition of 3,4-dihydroxyphenylpropionic acid, EDC, and NHS in a 1:0.1 molar ratio to hyaluronic acid, and the reaction was allowed to proceed for 1 hour. Finally, hyaluronic acid aggregates were obtained by dialysis and lyophilization. Hyaluronic acid aggregates were dissolved in pure water to prepare a hyaluronic acid aggregate solution with a concentration of 100 mg / mL. Then, degreased cotton yarn was soaked in the chitosan aggregate solution for 72 hours. After being removed, excess solution was absorbed with absorbent paper, and the yarn was freeze-dried to obtain hyaluronic acid aggregate composite gauze.

[0034] Example 2

[0035] 0.01 g of chitosan was dissolved in 100 mL of hydrochloric acid with a pH of 2.0 to prepare a chitosan aqueous solution with a concentration of 0.1 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Then, daunoic anhydride was added at a molar ratio of 1:0.1 to chitosan, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain a chitosan assembly solution. Nitrogen gas was purged into a chitosan assembly solution with a concentration of 0.05 mg / mL. Then, 3,4,5-trihydroxybenzoic acid, EDC, and Hobt were added sequentially in a 1:10 molar ratio to chitosan, and the reaction was allowed to proceed for 24 hours. Finally, chitosan aggregates were obtained by dialysis and lyophilization. Chitosan aggregates were dissolved in pure water to prepare a chitosan aggregate solution with a concentration of 0.1 mg / mL. Medical gauze was then immersed in the solution for 1 second, removed, and excess solution was absorbed with absorbent paper. The gauze was then air-dried to obtain chitosan aggregate composite gauze.

[0036] Example 3

[0037] 0.01 g of hydroxymethyl chitosan was dissolved in 100 mL of hydrochloric acid with a pH of 2.0 to prepare an aqueous solution of hydroxymethyl chitosan with a concentration of 0.1 mg / mL. After adding an equal volume of ethanol, the solution was heated to 75 °C. Subsequently, hexadecanoic anhydride was added at a molar ratio of 1:0.1 to hydroxymethyl chitosan, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain a hydroxymethyl chitosan assembly solution. Nitrogen gas was purged into a 0.05 mg / mL hydroxymethyl chitosan assembly solution, followed by the sequential addition of 4-carboxyphenylboronic acid, EDC, and DCC in a 1:10 molar ratio to hydroxymethyl chitosan, and the reaction was allowed to proceed for 24 hours. Finally, hydroxymethyl chitosan aggregates were obtained by dialysis and lyophilization. Hydroxymethyl chitosan aggregates were dissolved in pure water to prepare a hydroxymethyl chitosan aggregate solution with a concentration of 12 mg / mL. Nonwoven fabric was then soaked in the solution for 2 hours. After removal, excess solution was absorbed with absorbent paper, and the fabric was freeze-dried to obtain hydroxymethyl chitosan aggregate composite gauze.

[0038] Example 4

[0039] 10 g of sodium alginate was dissolved in 100 mL of hydrochloric acid with a pH of 6.5 to prepare a sodium alginate aqueous solution with a concentration of 100 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 30 °C. Then, octanoic acid and EDC were added at a molar ratio of 1:10 to sodium alginate, and the reaction was carried out for 1 hour. The solution was then cooled to room temperature to obtain a hyaluronic acid assembly solution. Nitrogen gas was purged into a sodium alginate assembly solution with a concentration of 50 mg / mL. Dopamine hydrochloride, EDC, and NHS were then added sequentially in a molar ratio of 1:0.1 to sodium alginate, and the reaction was allowed to proceed for 1 hour. Finally, sodium alginate aggregates were obtained by dialysis and lyophilization. Sodium alginate aggregates were dissolved in pure water to prepare a sodium alginate aggregate solution with a concentration of 10 mg / mL. Medical gauze was then soaked in the solution for 3 hours. After removal, excess solution was absorbed with absorbent paper and air-dried to obtain sodium alginate aggregate composite gauze.

[0040] Example 5

[0041] 0.1 g of carboxypropyl chitosan was dissolved in 100 mL of hydrochloric acid with a pH of 2.0 to prepare an aqueous solution of carboxypropyl chitosan with a concentration of 1.0 mg / mL. After adding an equal volume of ethanol, the solution was heated to 75 °C. Subsequently, dodecanoic acid and EDC were added at a molar ratio of 1:0.1 to carboxypropyl chitosan, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain a carboxypropyl chitosan assembly solution. Nitrogen gas was purged into a 0.05 mg / mL carboxypropyl chitosan assembly solution, followed by the addition of 3-aminophenyl borate salt, EDC, and DCC in a 1:10 molar ratio to hydroxymethyl chitosan, and the reaction was allowed to proceed for 24 hours. Finally, carboxypropyl chitosan aggregates were obtained by dialysis and lyophilization. Carboxypropyl chitosan aggregates were dissolved in pure water to prepare a carboxypropyl chitosan aggregate solution with a concentration of 7 mg / mL. Then, degreased cotton yarn was soaked in the solution for 4 hours. After being removed, excess solution was absorbed with absorbent paper, and the yarn was freeze-dried to obtain carboxypropyl chitosan aggregate composite gauze.

[0042] Example 6

[0043] 1.0 g of chitosan oligosaccharide was dissolved in 100 mL of hydrochloric acid with a pH of 2.0 to prepare a 10 mg / mL aqueous solution of chitosan oligosaccharide. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Subsequently, n-octylamine and EDC were added at a 1:1 molar ratio with chitosan oligosaccharide, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain a chitosan oligosaccharide assembly solution. Nitrogen gas was purged into a 5 mg / mL chitosan oligosaccharide assembly solution, followed by the sequential addition of 3-aminophenyl borate salt, EDC, and DCC in a 1:1 molar ratio to chitosan oligosaccharide, and the reaction was allowed to proceed for 24 hours. Finally, chitosan oligosaccharide aggregates were obtained by dialysis and lyophilization. Chitosan oligosaccharide aggregates were dissolved in pure water to prepare a chitosan oligosaccharide aggregate solution with a concentration of 15 mg / mL. Then, nonwoven fabric was soaked in the solution for 3 hours. After taking it out, the excess solution was absorbed with absorbent paper and air-dried to obtain chitosan oligosaccharide aggregate composite gauze.

[0044] Example 7

[0045] 1.0 g of aminohyaluronic acid was dissolved in 100 mL of hydrochloric acid with a pH of 5.0 to prepare an aqueous solution of aminohyaluronic acid with a concentration of 10 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Subsequently, n-octylamine and EDC were added in a 1:1 molar ratio with aminohyaluronic acid, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain an aminohyaluronic acid assembly solution. Nitrogen gas was purged into a 5 mg / mL aminohyaluronic acid assembly solution, followed by the sequential addition of 3-aminophenylborate salt, EDC, and DCC in a 1:1 molar ratio with aminohyaluronic acid, and the reaction was allowed to proceed for 24 hours. Finally, aminohyaluronic acid aggregates were obtained by dialysis and lyophilization. A amino hyaluronic acid coagulate was dissolved in pure water to prepare an amino hyaluronic acid coagulate solution with a concentration of 9 mg / mL. Then, degreased cotton yarn was soaked in the solution for 5 hours. After removing the yarn, excess solution was absorbed with absorbent paper, and the yarn was freeze-dried to obtain amino hyaluronic acid coagulate composite gauze.

[0046] Example 8

[0047] 5.0 g of aminohyaluronic acid was dissolved in 100 mL of hydrochloric acid with a pH of 4.0 to prepare an aqueous solution of aminohyaluronic acid with a concentration of 50 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Subsequently, n-octylamine and EDC were added at a molar ratio of 1:1 with aminohyaluronic acid, and the reaction was carried out for 12 hours. The solution was then cooled to room temperature to obtain an aminohyaluronic acid assembly solution. Nitrogen gas was purged into a 25 mg / mL aminohyaluronic acid assembly solution, followed by the sequential addition of 3-aminophenylborate salt, EDC, and DCC in a 1:2 molar ratio to aminohyaluronic acid, and the reaction was allowed to proceed for 12 hours. Finally, aminohyaluronic acid aggregates were obtained by dialysis and lyophilization. An amino hyaluronic acid coagulate was dissolved in pure water to prepare an amino hyaluronic acid coagulate solution with a concentration of 12 mg / mL. The non-woven fabric was then soaked in the solution for 4 hours. After removal, the excess solution was absorbed with absorbent paper and air-dried to obtain an amino hyaluronic acid coagulate composite gauze.

[0048] Example 9

[0049] 1.0 g of carboxymethyl dextran was dissolved in 100 mL of hydrochloric acid with a pH of 2.0 to prepare a 10 mg / mL aqueous solution of carboxymethyl dextran. After adding an equal volume of ethanol, the solution was heated to 75 °C. Subsequently, dodecanoic acid and EDC were added at a 1:1 molar ratio with carboxymethyl dextran, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain a carboxymethyl dextran assembly solution. Nitrogen gas was purged into a 5 mg / mL carboxymethyl dextran assembly solution, followed by the sequential addition of 3-aminophenyl borate salt, EDC, and DCC in a 1:1 molar ratio to carboxymethyl dextran, and the reaction was allowed to proceed for 8 hours. Finally, carboxymethyl dextran aggregates were obtained by dialysis and lyophilization. A carboxymethyl dextran aggregate solution with a concentration of 9 mg / mL was prepared by dissolving carboxymethyl dextran aggregates in pure water. Medical gauze was then soaked in the solution for 2 hours. After removal, excess solution was absorbed with absorbent paper, and the gauze was freeze-dried to obtain carboxymethyl dextran aggregate composite gauze.

[0050] Example 10

[0051] 5.0 g of cellulose nanocrystals were dissolved in 100 mL of hydrochloric acid with a pH of 4.0 to prepare an aqueous solution of cellulose nanocrystals with a concentration of 50 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Subsequently, dodecylamine and EDC were added at a molar ratio of 1:0.5 to the cellulose nanocrystals, and the reaction was carried out for 12 hours. The solution was then cooled to room temperature to obtain a cellulose nanocrystal assembly solution. Nitrogen gas was purged into a 25 mg / mL solution of cellulose nanocrystal assemblies. Then, 3-aminophenylborate salt, EDC, and DCC were added sequentially in a molar ratio of 1:0.5 to the cellulose nanocrystals, and the reaction was allowed to proceed for 12 hours. Finally, cellulose nanocrystal aggregates were obtained by dialysis and lyophilization. A cellulose nanocrystal aggregate solution with a concentration of 12 mg / mL was prepared by dissolving cellulose nanocrystal aggregates in pure water. The blended gauze was then soaked in the solution for 3 hours. After removal, excess solution was absorbed with absorbent paper and air-dried to obtain cellulose nanocrystal aggregate composite gauze.

[0052] Example 11

[0053] 5.0 g of hydroxymethyl cellulose was dissolved in 100 mL of hydrochloric acid with a pH of 4.0 to prepare an aqueous solution of hydroxymethyl cellulose with a concentration of 50 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Subsequently, hexadecylamine and EDC were added at a molar ratio of 1:0.5 to hydroxymethyl cellulose, and the reaction was carried out for 12 hours. The solution was then cooled to room temperature to obtain a solution of hydroxymethyl cellulose assembly. Nitrogen gas was purged into a 25 mg / mL solution of hydroxymethyl cellulose (HMC), followed by the sequential addition of 3-aminophenyl borate, EDC, and DCC in a molar ratio of 1:0.5 to HMC, and the reaction was allowed to proceed for 12 hours. Finally, HMC aggregates were obtained by dialysis and lyophilization. A hydroxymethyl cellulose (HMC) aggregate solution with a concentration of 10 mg / mL was prepared by dissolving HMC aggregate in pure water. The nonwoven fabric was then soaked in the solution for 1.5 hours. After removal, the excess solution was absorbed with absorbent paper, and the fabric was freeze-dried to obtain HMC aggregate composite gauze.

[0054] Example 12

[0055] 1.0 g of hydroxypropyl cellulose was dissolved in 100 mL of hydrochloric acid with a pH of 2.0 to prepare an aqueous solution of hydroxypropyl cellulose with a concentration of 10 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Subsequently, n-octadecylamine and EDC were added in a 1:1 molar ratio with hydroxypropyl cellulose, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain a solution of hydroxypropyl cellulose assembly. Nitrogen gas was purged into a 5 mg / mL hydroxypropyl cellulose assembly solution, followed by the sequential addition of 3-aminophenyl borate, EDC, and DCC in a 1:1 molar ratio to hydroxypropyl cellulose, and the reaction was allowed to proceed for 24 hours. Finally, hydroxypropyl cellulose aggregates were obtained by dialysis and lyophilization. Hydroxypropyl cellulose aggregates were dissolved in pure water to prepare a hydroxypropyl cellulose aggregate solution with a concentration of 13 mg / mL. Knitted gauze was then soaked in the solution for 3 hours. After removal, excess solution was absorbed with absorbent paper and air-dried to obtain hydroxypropyl cellulose aggregate composite gauze.

[0056] Example 13

[0057] 1.0 g of glycosaminoglycan was dissolved in 100 mL of hydrochloric acid with a pH of 2.0 to prepare a glycosaminoglycan aqueous solution with a concentration of 10 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Subsequently, n-octadecylamine and EDC were added at a molar ratio of 1:1 with glycosaminoglycan, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain a glycosaminoglycan assembly solution. Nitrogen gas was purged into a 5 mg / mL glycosaminoglycan assembly solution, followed by the sequential addition of 3-aminophenyl borate, EDC, and DCC in a 1:1 molar ratio to glycosaminoglycan, and the reaction was allowed to proceed for 8 hours. Finally, glycosaminoglycan aggregates were obtained by dialysis and lyophilization. A 10 mg / mL glycosaminoglycan solution was prepared by dissolving glycosaminoglycan aggregates in pure water. Medical gauze was then placed on a spin coater and the glycosaminoglycan aggregate solution was evenly spin-coated at a speed of 3000 rpm for 5 minutes. After removal, excess solution was absorbed with absorbent paper and air-dried to obtain glycosaminoglycan aggregate composite gauze.

[0058] Example 14

[0059] 1.0 g of hydroxypropyl cellulose was dissolved in 100 mL of hydrochloric acid with a pH of 2.0 to prepare an aqueous solution of hydroxypropyl cellulose with a concentration of 10 mg / mL. After adding an equal volume of ethanol, the temperature was raised to 75 °C. Subsequently, n-octadecylamine and EDC were added in a 1:1 molar ratio with hydroxypropyl cellulose, and the reaction was carried out for 24 hours. The solution was then cooled to room temperature to obtain a solution of hydroxypropyl cellulose assembly. Nitrogen gas was purged into a 5 mg / mL hydroxypropyl cellulose assembly solution, followed by the sequential addition of 3-aminophenyl borate, EDC, and DCC in a 1:1 molar ratio to hydroxypropyl cellulose, and the reaction was allowed to proceed for 10 hours. Finally, hydroxypropyl cellulose aggregates were obtained by dialysis and lyophilization. Hydroxypropyl cellulose aggregates were dissolved in pure water to prepare a hydroxypropyl cellulose aggregate solution with a concentration of 12 mg / mL. Then, medical gauze was placed under a spraying machine and the hydroxypropyl cellulose aggregate solution was sprayed evenly. The spraying pressure was 2 bar and the spraying time was 3 minutes. After removal, the excess solution was absorbed with absorbent paper and freeze-dried to obtain chitosan aggregate composite gauze.

[0060] Example 15

[0061] The overall hemostatic performance of the hemostatic gauze was evaluated using a rat liver hemorrhage model. A 6 mm diameter, 2 mm deep lesion was created in the rat liver using a biopsy puncture device, and a hemostatic spray was immediately applied to the bleeding site. The hemostasis time and blood loss in the rat liver were recorded.

[0062] Experimental results showed that the average hemostasis time for rat livers without any hemostatic material was 530 seconds, with a blood loss of 8.34 g; the average hemostasis time for rat livers using medical cotton gauze was 305 seconds, with a blood loss of 5.13 g; while the average hemostasis time for rat livers using polysaccharide aggregate composite hemostatic gauze was 30 seconds, with a blood loss of only 0.45 g. Compared to medical cotton gauze, the polysaccharide aggregate composite hemostatic gauze exhibited shorter hemostasis time and minimal blood loss, demonstrating excellent hemostatic effect in the rat liver hemorrhage model. The polysaccharide aggregate composite hemostatic gauze of this invention possesses technological innovation and significant advantages, solving the application challenges of existing hemostatic materials in scenarios of massive bleeding and providing a more efficient and safer hemostatic solution. Its production process is simple and low-cost, and it has broad market demand, especially in emergency care, military, and disaster relief fields, showing enormous market potential. Therefore, this invention has high prospects for industrial application, significant potential for patent commercialization, and is suitable for further development and promotion.

[0063] The practicality of the technical solution of this invention is as follows: 1. Technological advantages Highly effective hemostatic properties: This hemostatic gauze combines the excellent blood absorbency and hydrophilicity of polysaccharide aggregates with the capillary effect of gauze, which can quickly activate the coagulation process and seal the wound, thereby providing rapid hemostasis in cases of massive bleeding.

[0064] Polysaccharide aggregates, through their self-assembly properties, can form high-strength structures in a short time, enhancing the mechanical strength and resistance to high-pressure blood flow of hemostatic gauze, thus avoiding the problem of traditional gauze easily failing during massive bleeding.

[0065] Biocompatibility and Degradability: Polysaccharide materials are naturally biocompatible and degradable, gradually degrading in the body after use without producing toxic side effects, reducing the risk of tissue adhesion or rejection reactions. The polysaccharide materials used in this invention, such as chitosan, not only have good biodegradability but also possess natural antibacterial properties, helping to reduce the risk of infection and meeting the high requirements of modern medicine for wound care materials.

[0066] Adjustable blood absorption and tissue adhesion: By optimizing the preparation process of polysaccharide aggregates, their blood absorption and tissue adhesion can be adjusted to ensure optimal effectiveness in different types of wounds and bleeding conditions. The combination of polysaccharide aggregates with gauze, such as impregnation, spraying, or spin coating, allows the gauze to maintain its traditional functions while enhancing hemostatic efficacy and ease of use.

[0067] 2. Performance Indicators

[0068] Hemostasis speed and effectiveness: Experimental data show that the polysaccharide aggregate composite hemostatic gauze can rapidly form a blood clot within 5 seconds after contact with blood, significantly improving the speed of hemostasis and meeting the needs of rapid hemostasis in emergency situations. Compared with traditional medical gauze, the hemostatic gauze of this invention can better seal wounds, effectively resist high-pressure blood flow, and is suitable for complex trauma scenarios such as massive bleeding and deep wounds.

[0069] Mechanical properties: The composite hemostatic gauze has significantly improved tensile and compressive strength, ensuring that it is not easily torn or punctured during use, and can maintain hemostasis for a longer period of time, especially in cases of massive bleeding.

[0070] Biodegradability and safety: In vitro and in vivo tests have shown that the composite hemostatic gauze completely degrades within one month of application without causing any negative impact on the human body, meeting biosafety standards. No subsequent removal is required, reducing the complexity of wound cleaning.

[0071] 3. Production Implementation and Industrial Application Prospects

[0072] Feasibility of the production process: The preparation method of this invention involves common chemical modification techniques and standardized production processes. Raw materials such as chitosan have low costs and are widely available, making them easy to scale up for production. The composite methods of gauze and polysaccharide aggregates, such as impregnation, spraying, or spin coating, are simple processes applicable to existing textile and medical product production lines, requiring no complex equipment investment, thus reducing production costs and technological barriers.

[0073] Market Demand: Since massive bleeding remains a leading cause of death among trauma victims, there is a widespread demand for highly effective hemostatic materials, particularly in emergency care, military operations, and disaster relief. The composite hemostatic gauze of this invention can meet these needs and has a promising market prospect.

[0074] In modern medicine, hemostatic materials are constantly being innovated and improved, and patients have a growing demand for more efficient and safer hemostatic products. In particular, the natural advantages of polysaccharide materials meet multiple medical needs, including biocompatibility, biodegradability, and efficient hemostasis, making them highly attractive in the market.

[0075] Potential application areas: First aid and battlefield medicine - can be widely used in first aid kits, military medical equipment, rescue vehicles and other scenarios; Disaster relief and field medicine - in disaster relief sites or outdoor activities, composite hemostatic gauze can provide immediate hemostasis for the wounded, greatly improving the survival rate; Hospitals and clinics - can be used as a routine wound hemostatic material in surgery, wound treatment and postoperative care.

[0076] Patent commercialization prospects: This technology has strong commercialization potential and can be used to collaborate with medical device manufacturers and emergency equipment suppliers to further promote its marketization. This invention can also facilitate cross-industry collaborations with textiles, medical materials, and biomaterials, expanding application scenarios and enhancing market competitiveness.

[0077] The preferred embodiments of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the scope of protection defined by the claims.

Claims

1. A polysaccharide aggregate composite hemostatic gauze, characterized in that, The polysaccharide aggregate composite hemostatic gauze is made by composite polysaccharide aggregates onto the surface of gauze.

2. The polysaccharide aggregate composite hemostatic gauze according to claim 1, characterized in that, The polysaccharide is one or more of chitosan, hydroxymethyl chitosan, carboxypropyl chitosan, chitosan oligosaccharide, sodium alginate, hyaluronic acid, aminohyaluronic acid, cellulose nanocrystals, hydroxymethyl cellulose, hydroxypropyl cellulose, carboxyglucan, or aminoglucan.

3. A method for preparing the polysaccharide aggregate composite hemostatic gauze according to claim 1, characterized in that, Includes the following steps: (1) Preparation of polysaccharide aggregates Step 1: Add hydrophobic molecules and activators to the water-soluble polysaccharide solution, and graft the hydrophobic functional substances onto the main chain of the polysaccharide macromolecule to obtain a polysaccharide assembly modified with hydrophobic molecules. Step 2: Add adhesive molecules and activators that can mediate supramolecular forces to the polysaccharide assembly solution prepared in Step 1, and modify them onto the polysaccharide assembly to obtain a polysaccharide aggregate modified with hydrophobic and adhesive molecules. (2) Preparation of polysaccharide aggregate composite hemostatic gauze Step 3: The polysaccharide aggregate solution obtained in Step 2 is brought into contact with gauze for a certain period of time by impregnation, spraying or spin coating, and finally the polysaccharide aggregate composite hemostatic gauze is obtained by freeze drying or air drying.

4. The method for preparing the polysaccharide aggregate composite hemostatic gauze according to claim 3, characterized in that, In step 1, the water-soluble polysaccharide is one or more of chitosan, hydroxymethyl chitosan, carboxypropyl chitosan, chitosan oligosaccharide, sodium alginate, hyaluronic acid, aminohyaluronic acid, cellulose nanocrystals, hydroxymethyl cellulose, hydroxypropyl cellulose, carboxyglucan, or aminoglucan, and the concentration of the water-soluble polysaccharide is 0.1-100 mg / mL.

5. The method for preparing the polysaccharide aggregate composite hemostatic gauze according to claim 3, characterized in that, In step 1, the hydrophobic molecule is one or more of the following: octanoic acid, dodecanoic acid, hexadecanoic acid, octanoic anhydride, dodecanoic anhydride, hexadecanoic anhydride, octylamine, dodecylamine, hexadecylamine, and octadecylamine.

6. The method for preparing the polysaccharide aggregate composite hemostatic gauze according to claim 3, characterized in that, In step 2, the adhesive molecule is one or more of the following: 3,4-dihydroxyphenylpropionic acid, 3,4,5-trihydroxybenzoic acid, 4-carboxyphenylboronic acid, dopamine hydrochloride, and 3-aminophenylboronic acid salt.

7. The method for preparing the polysaccharide aggregate composite hemostatic gauze according to claim 3, characterized in that, The activator in steps 1 and 2 is selected from one or more of EDC, NHS, Hobt and DCC.

8. The method for preparing the polysaccharide aggregate composite hemostatic gauze according to claim 3, characterized in that, In step 1, the molar ratio of hydrophobic molecules to polysaccharides is 0.1-10:1, and the molar ratio of polysaccharides to activators is 0.1-10:

1.

9. The method for preparing the polysaccharide aggregate composite hemostatic gauze according to claim 3, characterized in that, Step 2 includes: adding adhesive molecules and activators to the polysaccharide assembly solution prepared in step 1, modifying the polysaccharide assembly to obtain a polysaccharide aggregate modified with hydrophobic and adhesive molecules. The molar ratio of adhesive molecules to polysaccharides is 0.1-10:1, and the molar ratio of polysaccharides to activators is 0.1-10:

1.

10. The method for preparing the glycopolymer composite hemostatic gauze according to claim 3, characterized in that, In step 3, the concentration of the polysaccharide aggregate solution is 0.1-1000 mg / mL; the gauze is selected from one or more of the following: cotton gauze, medical gauze, degreased gauze, chemical fiber gauze, non-woven fabric, knitted gauze, woven gauze, and blended gauze.