Hemostatic composition, preparation method thereof and hemostatic product

Abstract

The invention provides a hemostatic composition, a preparation method thereof and a hemostatic product. The hemostatic composition is prepared from the following raw material components in parts by mass: 0.01 to 0.5 part of cannabidiol, 10 to 150 parts of tannic acid modified carboxymethyl chitosan and 5 to 250 parts of crosslinked starch. The tannic acid modified carboxymethyl chitosan is prepared from the following raw material components in parts by mass: 45 to 55 parts of carboxymethyl chitosan and 0.5 to 1.5 parts of tannic acid. The cross-linked starch is prepared from the following raw materials in parts by mass: 95 to 105 parts of carboxymethyl enzymolysis starch and 2 to 5 parts of sodium trimetaphosphate. The hemostatic composition has a good hemostatic effect, and when the hemostatic composition is used in hemostatic products, the hemostatic products can have a good hemostatic effect.

Description

Technical Field

[0001] The present invention relates to the technical field of hemostatic products, and particularly to a hemostatic composition, a preparation method thereof, and a hemostatic product. Background Art

[0002] In many medical scenarios such as surgical operations and trauma first aid, rapid and effective hemostasis is a crucial link. Traditional hemostatic materials such as gauze and bandages are widely used, but in the face of some complex bleeding situations, especially large-area bleeding or bleeding sites that are difficult to compress for hemostasis, the hemostatic effect is often unsatisfactory. In recent years, with the continuous integration of materials science and biotechnology, new hemostatic materials have become a research hotspot. However, many existing hemostatic materials still have problems such as insufficiently fast blood coagulation speed, poor biocompatibility, easy infection, or adverse effects caused by residues in the body. Therefore, there is an urgent need to develop a hemostatic product with excellent comprehensive performance. Summary of the Invention

[0003] Based on the above problems, the present invention provides a hemostatic composition. The hemostatic composition has the effect of rapid blood coagulation, and when used in hemostatic products, it can effectively promote the development of rapid hemostasis products.

[0004] To achieve the above object, the present invention adopts the following technical solutions: A hemostatic composition, the raw materials of which include the following components in parts by mass: 0.01 - 0.5 part of cannabidiol, 10 - 150 parts of tannic acid-modified carboxymethyl chitosan, and 5 - 250 parts of cross-linked starch; the raw materials of the tannic acid-modified carboxymethyl chitosan include the following components in parts by mass: 45 - 55 parts of carboxymethyl chitosan and 0.5 - 1.5 parts of tannic acid. The raw materials of the cross-linked starch include the following components in parts by mass: 95 - 105 parts of carboxymethyl enzymatically hydrolyzed starch and 2 - 5 parts of sodium trimetaphosphate.

[0005] Optionally, the raw materials of the carboxymethyl enzymatically hydrolyzed starch include the following components in parts by mass: 22 - 30 parts of enzymatically hydrolyzed starch and 15 - 20 parts of chloroacetic acid.

[0006] Optionally, the raw materials of the enzymatically hydrolyzed starch include the following components in parts by mass: 20 - 25 parts of potato starch, 0.2 - 0.5 part of glucoamylase, and 0.05 - 0.1 part of α-amylase.

[0007] Optionally, the mass ratio of the glucoamylase to the α-amylase is (2 - 5):1; The sum of the mass parts of the glucoamylase and the α-amylase is 0.25 - 0.5 part.

[0008] Optionally, the raw materials of the hemostatic composition include the following components in parts by mass: 0.05-0.2 parts of cannabidiol, 50-100 parts of tannic acid-modified carboxymethyl chitosan, and 50-150 parts of cross-linked starch; The raw materials of the tannic acid-modified carboxymethyl chitosan include the following components in parts by mass: 48-52 parts of carboxymethyl chitosan and 0.8-1.2 parts of tannic acid; The raw materials of the cross-linked starch include the following components in parts by mass: 98-102 parts of carboxymethyl hydrolyzed starch and 2.5-4 parts of sodium trimetaphosphate; The raw materials of the carboxymethyl hydrolyzed starch include the following components in parts by mass: 24-28 parts of hydrolyzed starch and 16-19 parts of chloroacetic acid; The raw materials of the hydrolyzed starch include the following components in parts by mass: 21-23 parts of potato starch, 0.3-0.4 parts of glucoamylase, and 0.06-0.09 parts of α-amylase.

[0009] Optionally, the raw materials of the hemostatic composition include the following components in parts by mass: 0.08-0.12 parts of cannabidiol, 70-80 parts of tannic acid-modified carboxymethyl chitosan, and 60-100 parts of cross-linked starch; The raw materials of the tannic acid-modified carboxymethyl chitosan include the following components in parts by mass: 50 parts of carboxymethyl chitosan and 1 part of tannic acid; The raw materials of the cross-linked starch include the following components in parts by mass: 100 parts of carboxymethyl hydrolyzed starch and 3 parts of sodium trimetaphosphate; The raw materials of the carboxymethyl hydrolyzed starch include the following components in parts by mass: 25 parts of hydrolyzed starch and 18 parts of chloroacetic acid; The raw materials of the hydrolyzed starch include the following components in parts by mass: 21 parts of potato starch, 0.32 parts of glucoamylase, and 0.08 parts of α-amylase.

[0010] Optionally, it is characterized by including the following steps: Preparation of the tannic acid-modified carboxymethyl chitosan: Dissolve the carboxymethyl chitosan in water to obtain an aqueous carboxymethyl chitosan solution, where the mass percentage of the carboxymethyl chitosan in the aqueous carboxymethyl chitosan solution is 2% - 6%; dissolve the tannic acid in water to obtain an aqueous tannic acid solution, where the mass percentage of the tannic acid in the aqueous tannic acid solution is 2% - 6%; slowly drip the aqueous tannic acid solution into the aqueous carboxymethyl chitosan solution, react at 55 - 65 °C for 2 - 4 h, maintain the pH value of the reaction solution at 7 - 9 during the reaction process, and introduce air during the reaction process. The volume ratio of the aqueous tannic acid solution to the aqueous carboxymethyl chitosan solution is (45 - 55):1; after the reaction, perform dialysis treatment on the reaction solution, and then freeze-dry to obtain the tannic acid-modified carboxymethyl chitosan; Preparation of the cross-linked starch: Dissolve the carboxymethyl enzymatically hydrolyzed starch in water to obtain a carboxymethyl enzymatically hydrolyzed starch solution, adjust the pH value of the carboxymethyl enzymatically hydrolyzed starch solution to 9.5 - 10.5, and then add the sodium trimetaphosphate to form an aqueous phase; mix the oil-phase matrix and the emulsifier, where the mass percentage of the emulsifier in the oil-phase matrix is 0.5% - 2%, to obtain an oil phase; drip the aqueous phase into the oil phase and react at 55 - 65 °C for 5 - 7 h; after the reaction, wash the reaction solution with a washing solution, where the washing solution includes at least one of acetone, petroleum ether, sodium chloride aqueous solution, and ethanol, and dry at 45 - 55 °C after washing to obtain the cross-linked starch: Preparation of the hemostatic composition: Add the tannic acid-modified carboxymethyl chitosan and the cross-linked starch into the cannabidiol solution and mix. The cannabidiol solution includes the cannabidiol, and then remove the solvent in the cannabidiol solution to obtain the hemostatic composition.

[0011] Optionally, the carboxymethyl enzymatically hydrolyzed starch is prepared by the following method: Preparation of the enzymatically hydrolyzed starch: Dissolve the potato starch in an acetic acid-sodium acetate buffer solution with a pH value of 3.5 - 4.5, and then add glucoamylase and α-amylase, and react at 45 - 55 °C for 6 - 10 h. The mass parts of the potato starch are 20 - 25 parts, the mass parts of the glucoamylase are 0.2 - 0.5 parts, and the mass parts of the α-amylase are 0.05 - 0.1 parts. The mass ratio of the glucoamylase to the α-amylase is (2 - 5):1, and the sum of the mass parts of the glucoamylase and the α-amylase is 0.25 - 0.5. After the reaction, wash and filter the product, and vacuum-dry the solid-phase product at 45 - 55 °C to obtain the enzymatically hydrolyzed starch; Dissolve sodium hydroxide in an ethanol - aqueous solution to obtain a sodium hydroxide solution. The volume percentage of ethanol in the ethanol - aqueous solution is 90% - 95%. In the sodium hydroxide solution, the mass percentage of sodium hydroxide is 2% - 4%. Add the enzymatically hydrolyzed starch to the sodium hydroxide solution, and the mass of the enzymatically hydrolyzed starch is equal to that of the sodium hydroxide. Carry out a reflux reaction at 45 - 55 °C for 25 - 35 min, then add chloroacetic acid to the reaction solution and carry out a reflux reaction at 45 - 55 °C for 2 - 4 h. The mass portion of the enzymatically hydrolyzed starch is 22 - 30 parts, and the mass portion of the chloroacetic acid is 15 - 20 parts. After the reaction, wash and filter the reaction product, and vacuum - dry the solid phase product at 45 - 55 °C to obtain carboxymethyl enzymatically hydrolyzed starch.

[0012] Optionally, the dropping rate of slowly dropping the tannic acid aqueous solution into the carboxymethyl chitosan aqueous solution is 1 - 5 mL / min; The oil - phase matrix includes liquid paraffin; the emulsifier includes Span 80.

[0013] A hemostatic product includes the hemostatic composition.

[0014] Beneficial effects In the hemostatic composition of the present invention, through the synergistic cooperation of each raw material, a hemostatic composition with rapid hemostasis and good biocompatibility can be obtained. Using this composition in a hemostatic product can effectively promote the development of rapid - hemostasis products. Specific embodiments

[0015] An embodiment of the present invention provides a hemostatic composition, and its raw materials include the following components in parts by mass: cannabidiol 0.01 - 0.5 parts, tannic acid - modified carboxymethyl chitosan 10 - 150 parts, and cross - linked starch 5 - 250 parts; the raw materials of the tannic acid - modified carboxymethyl chitosan include the following components in parts by mass: carboxymethyl chitosan 45 - 55 parts, tannic acid 0.5 - 1.5 parts. The raw materials of the cross - linked starch include the following components in parts by mass: carboxymethyl enzymatically hydrolyzed starch 95 - 105 parts, sodium trimetaphosphate 2 - 5 parts.

[0016] In the composition of this embodiment, each component cooperates with each other to obtain the effect of rapid blood coagulation. At the same time, this composition has good antibacterial properties and good biocompatibility.

[0017] Specifically, cannabidiol has certain anti - inflammatory and tissue - repair - promoting effects. It can regulate the body's immune response, reduce the damage of the inflammatory response to tissues, create a good environment for wound healing, thus indirectly contributing to hemostasis and wound recovery. At the same time, it has good biocompatibility itself and will not cause obvious immune rejection reactions.

[0018] Among the tannic acid-modified carboxymethyl chitosan, carboxymethyl chitosan is a water-soluble chitosan derivative with good biocompatibility, biodegradability and hemostatic properties. It can promote the adhesion and aggregation of platelets and accelerate the coagulation process by interacting with red blood cells and platelets in the blood, thereby achieving the purpose of hemostasis. At the same time, carboxymethyl chitosan can also form a protective film on the wound surface to prevent bacterial infection and promote wound healing. Tannic acid has a convergence effect, which can coagulate the protein in the wound tissue to form a protective film and reduce blood exudation. In addition, tannic acid also has certain antibacterial properties, which can prevent wound infection. When combined with carboxymethyl chitosan, it further improves the effect of hemostasis and wound healing. Moreover, the introduction of tannic acid can improve the performance of carboxymethyl chitosan and make it more compatible in the body.

[0019] Among cross-linked starches, carboxymethyl enzymatic starch can be a product of starch modified by enzymatic hydrolysis and carboxymethylation, and has good water solubility and biocompatibility. It can absorb water from the blood at the wound site to form a gel-like substance, thereby physically blocking the wound and preventing blood from flowing out. At the same time, this gel-like substance can also provide a moist environment for wound healing, which is conducive to cell migration and tissue repair. As a cross-linking agent, sodium trimetaphosphate can cause cross-linking reactions between carboxymethyl enzymatic starch molecules to form a three-dimensional network structure. This structure can increase the stability and mechanical strength of starch, so that it can better play a hemostatic and protective role at the wound site, and help maintain the stability of the local microenvironment of the wound and improve biocompatibility.

[0020] In some embodiments, the mass fraction of cannabidiol in the raw materials of the hemostatic composition can be 0.01 parts, 0.05 parts, 0.1 parts, 0.15 parts, 0.2 parts, 0.25 parts, 0.3 parts, 0.35 parts, 0.4 parts, 0.45 parts, 0.5 parts, etc. It can be understood that the mass fraction of cannabidiol can also be appropriately selected within the range of 0.01-0.5 parts.

[0021] In some embodiments, in the raw materials of the hemostatic composition, the mass fraction of tannic acid-modified carboxymethyl chitosan can be 10 parts, 20 parts, 30 parts, 40 parts, 50 parts, 60 parts, 70 parts, 80 parts, 90 parts, 100 parts, 110 parts, 120 parts, 130 parts, 140 parts, 150 parts, etc. It can be understood that the mass fraction of tannic acid-modified carboxymethyl chitosan can also be appropriately selected within the range of 10-150 parts.

[0022] In some embodiments, the mass fraction of cross-linked starch in the raw materials of the hemostatic composition can be 5 parts, 10 parts, 50 parts, 100 parts, 150 parts, 200 parts, 250 parts, etc. It is understandable that the mass fraction of cross-linked starch can also be appropriately selected within the range of 5-250 parts.

[0023] In some embodiments, the raw materials of the hemostatic composition are the following components in mass parts: 0.01-0.5 parts of cannabidiol, 10-150 parts of tannic acid modified carboxymethyl chitosan and 5-250 parts of cross-linked starch. It is understood that the mass parts of each component can be selected accordingly from the above content.

[0024] In some embodiments, the raw materials of carboxymethyl enzymatic starch include the following components in parts by weight: 22-30 parts of enzymatic starch and 15-20 parts of chloroacetic acid.

[0025] Chloroacetic acid is used to modify enzymatic starch by carboxylmethylation. The introduction of carboxylmethyl groups gives starch molecules a negative charge. This charge helps to electrostatically attract positively charged components in the blood (such as platelets, coagulation factors, etc.), thereby accelerating platelet aggregation and coagulation factor activation, promoting blood coagulation, and achieving rapid hemostasis. At the same time, carboxylmethylation can also improve the water solubility and stability of starch, so that it can play a better role in wounds. In the process of carboxylmethylation of enzymatic starch by chloroacetic acid, the reaction conditions are relatively mild, and the modified carboxymethyl enzymatic starch has better hydrophilicity and biological activity, and is closer to the biological molecular structure of the human body itself. This structural similarity enables it to better interact with human tissues and cells, reduce foreign body reactions, and thus show good biocompatibility.

[0026] Optionally, in the raw material of carboxymethyl enzymatic starch, the mass parts of enzymatic starch can be 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, etc. It is understandable that the enzymatic starch can also be appropriately selected within 22-30 parts.

[0027] Optionally, in the raw material of carboxymethyl enzymolyzed starch, the mass parts of chloroacetic acid can be 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, etc. It is understandable that chloroacetic acid can also be appropriately selected within 15-20 parts.

[0028] In some embodiments, the raw materials for enzymatic starch hydrolysis include the following components in parts by weight: 20-25 parts of potato starch, 0.2-0.5 parts of saccharifying enzyme, and 0.05-0.1 parts of α-amylase.

[0029] Potato starch is a natural polysaccharide with a wide range of sources. During the hemostasis process, it can serve as a physical barrier, quickly covering the wound surface and initially preventing blood from flowing out. At the same time, its granular structure helps to adsorb platelets and coagulation factors in the blood, promoting platelet aggregation and initiating the coagulation process. Meanwhile, as a natural biological macromolecule, potato starch itself has good biocompatibility. It is a substance that the human body can metabolize and utilize, and will not cause immune reactions or other adverse reactions.

[0030] Two enzymes, glucoamylase and α-amylase, are used for enzymatic hydrolysis of potato starch. Glucoamylase acts on the non-reducing end of starch, gradually hydrolyzing it into sugars such as glucose; α-amylase randomly acts on the α-1,4-glycosidic bonds inside the starch, breaking the long starch chains and generating dextrins and oligosaccharides with smaller molecules. Through the synergistic action of these two enzymes, the structure of potato starch is changed, making it more easily absorbed and metabolized by the human body. At the same time, the products after enzymatic hydrolysis may have better hydrophilicity and biological activity, being able to interact better with the components in the blood and accelerating the coagulation process. Moreover, their enzymatic hydrolysis process of potato starch is a mild biochemical reaction, which will not introduce substances harmful to the human body, and the enzymatic hydrolysis products are more easily absorbed and utilized by the human body, further improving the biocompatibility of the material.

[0031] In some embodiments, in the raw materials for enzymatically hydrolyzed starch, the mass parts of potato starch can be 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, etc. It can be understood that other suitable selections can also be made for the mass parts of potato starch within the range of 20 - 25 parts.

[0032] In some embodiments, in the raw materials for enzymatically hydrolyzed starch, the mass parts of glucoamylase can be 0.2 parts, 0.3 parts, 0.4 parts, 0.5 parts, etc. It can be understood that other suitable selections can also be made for the mass parts of glucoamylase within the range of 0.2 - 0.5 parts.

[0033] In some embodiments, in the raw materials for enzymatically hydrolyzed starch, the mass parts of α-amylase can be 0.05 parts, 0.06 parts, 0.07 parts, 0.08 parts, 0.09 parts, 0.1 parts, etc. It can be understood that other suitable selections can also be made for the mass parts of α-amylase within the range of 0.05 - 0.1 parts.

[0034] Furthermore, the mass ratio of glucoamylase to α-amylase is (2 - 5) : 1. For example, the mass ratio of glucoamylase to α-amylase can be 2 : 1, 2.5 : 1, 3 : 1, 3.5 : 1, 4 : 1, 4.5 : 1, 5 : 1, etc. It can be understood that other suitable selections can also be made for the mass ratio of glucoamylase to α-amylase within the range of (2 - 5) : 1.

[0035] Furthermore, the sum of the mass parts of glucoamylase and α-amylase is 0.25 - 0.5 parts. For example, the sum of the mass parts of glucoamylase and α-amylase can be 0.25 parts, 0.3 parts, 0.35 parts, 0.4 parts, 0.45 parts, 0.5 parts, etc. It can be understood that other suitable selections can also be made within the range of 0.25 - 0.5 parts for the sum of the mass parts of glucoamylase and α-amylase.

[0036] In some embodiments, the raw materials of the hemostatic composition include the following components in parts by mass: cannabidiol 0.05 - 0.2 parts, tannic acid-modified carboxymethyl chitosan 50 - 100 parts, crosslinked starch 50 - 150 parts. The raw materials of tannic acid-modified carboxymethyl chitosan include the following components in parts by mass: carboxymethyl chitosan 48 - 52 parts, tannic acid 0.8 - 1.2 parts. The raw materials of crosslinked starch include the following components in parts by mass: carboxymethyl enzymatically hydrolyzed starch 98 - 102 parts, sodium trimetaphosphate 2.5 - 4 parts. The raw materials of carboxymethyl enzymatically hydrolyzed starch include the following components in parts by mass: enzymatically hydrolyzed starch 24 - 28 parts, chloroacetic acid 16 - 19 parts. The raw materials of enzymatically hydrolyzed starch include the following components in parts by mass: potato starch 21 - 23 parts, glucoamylase 0.3 - 0.4 parts, and α-amylase 0.06 - 0.09 parts.

[0037] Furthermore, the raw materials of the hemostatic composition include the following components in parts by mass: cannabidiol 0.08 - 0.12 parts, tannic acid-modified carboxymethyl chitosan 70 - 80 parts, crosslinked starch 60 - 100 parts. The raw materials of tannic acid-modified carboxymethyl chitosan include the following components in parts by mass: carboxymethyl chitosan 50 parts, tannic acid 1 part. The raw materials of crosslinked starch include the following components in parts by mass: carboxymethyl enzymatically hydrolyzed starch 100 parts, sodium trimetaphosphate 3 parts. The raw materials of carboxymethyl enzymatically hydrolyzed starch include the following components in parts by mass: enzymatically hydrolyzed starch 25 parts, chloroacetic acid 18 parts. The raw materials of enzymatically hydrolyzed starch include the following components in parts by mass: potato starch 21 parts, glucoamylase 0.32 parts, and α-amylase 0.08 parts.

[0038] Another embodiment of the present invention provides a method for preparing the above-mentioned hemostatic composition, comprising the following steps: S101: Preparation of tannic acid-modified carboxymethyl chitosan: Dissolve carboxymethyl chitosan in water to obtain an aqueous carboxymethyl chitosan solution, where the mass percentage of carboxymethyl chitosan in the aqueous carboxymethyl chitosan solution is 2% - 6%; dissolve tannic acid in water to obtain an aqueous tannic acid solution, where the mass percentage of tannic acid in the aqueous tannic acid solution is 2% - 6%; slowly drip the aqueous tannic acid solution into the aqueous carboxymethyl chitosan solution, react at 55 - 65 °C for 2 - 4 h, maintain the pH value of the reaction solution at 7 - 9 during the reaction process, and introduce air during the reaction process. The volume ratio of the aqueous tannic acid solution to the aqueous carboxymethyl chitosan solution is (45 - 55):1; after the reaction, dialyze the reaction solution and then freeze-dry to obtain tannic acid-modified carboxymethyl chitosan. Optionally, the dialysis treatment may include: Dialyze the reaction solution in deionized water for five days using a dialysis bag with a molecular weight cut-off of 1000 Da.

[0039] S102: Preparation of crosslinked starch: Dissolve carboxymethyl enzymatically hydrolyzed starch in water to obtain a carboxymethyl enzymatically hydrolyzed starch solution, adjust the pH value of the carboxymethyl enzymatically hydrolyzed starch solution to 9.5 - 10.5, and then add sodium trimetaphosphate to form an aqueous phase; mix an oil phase matrix and an emulsifier, where the mass percentage of the emulsifier in the oil phase matrix is 0.5% - 2%, to obtain an oil phase; drip the aqueous phase into the oil phase and react at 55 - 65 °C for 5 - 7 h; after the reaction, wash the reaction solution with a washing solution, where the washing solution includes at least one of acetone, petroleum ether, aqueous sodium chloride solution, and ethanol, and dry at 45 - 55 °C after washing to obtain crosslinked starch.

[0040] S103: Preparation of a hemostatic composition: Add tannic acid-modified carboxymethyl chitosan and crosslinked starch to a cannabidiol solution and mix. The cannabidiol solution contains cannabidiol, and then remove the solvent from the cannabidiol solution to obtain a hemostatic composition.

[0041] It can be understood that there is no special limitation on the order of S101 and S102. S101 can be carried out first and then S102, or S102 can be carried out first and then S101, or S101 and S102 can be carried out simultaneously.

[0042] Optionally, carboxymethyl enzymatically hydrolyzed starch can be prepared by the following method: S201: Preparation of enzymatically hydrolyzed starch: Dissolve potato starch in an acetic acid - sodium acetate buffer solution with a pH value of 3.5 - 4.5, then add glucoamylase and α - amylase, and react at 45 - 55 °C for 6 - 10 h. Among them, the mass parts of potato starch are 20 - 25 parts, the mass parts of glucoamylase are 0.2 - 0.5 parts, and the mass parts of α - amylase are 0.05 - 0.1 parts. The mass ratio of glucoamylase to α - amylase is (2 - 5):1, and the sum of the mass parts of glucoamylase and α - amylase is 0.25 - 0.5. After the reaction, wash the product (for example, it can be washed with ultrapure water), filter, and vacuum - dry the solid product at 45 - 55 °C to obtain enzymatically hydrolyzed starch; S202: Dissolve sodium hydroxide in an ethanol - aqueous solution to obtain a sodium hydroxide solution. The volume percentage of ethanol in the ethanol - aqueous solution is 90% - 95%, and the mass percentage of sodium hydroxide in the sodium hydroxide solution is 2% - 4%. Add enzymatically hydrolyzed starch to the sodium hydroxide solution, and the mass of enzymatically hydrolyzed starch is equal to that of sodium hydroxide. Reflux and react at 45 - 55 °C for 25 - 35 min, then add chloroacetic acid to the reaction solution and reflux and react at 45 - 55 °C for 2 - 4 h. The mass parts of enzymatically hydrolyzed starch are 22 - 30 parts, and the mass parts of chloroacetic acid are 15 - 20 parts. After the reaction, wash the reaction product (for example, it can be washed with absolute ethanol), filter, and vacuum - dry the solid product at 45 - 55 °C to obtain carboxymethylated enzymatically hydrolyzed starch.

[0043] Optionally, the dropping rate of the tannic acid aqueous solution slowly dropped into the carboxymethyl chitosan aqueous solution is 1 - 5 mL / min. For example, the dropping rate can be 1 mL / min, 2 mL / min, 3 mL / min, 4 mL / min, 5 mL / min, etc.

[0044] In some embodiments, the oil - phase matrix includes liquid paraffin; the emulsifier includes Span 80.

[0045] This application also provides a hemostatic product in one embodiment. The hemostatic product includes the above - mentioned hemostatic composition. The hemostatic product has a good rapid hemostasis effect and good biocompatibility.

[0046] Optionally, the hemostatic product includes a hemostatic dressing.

[0047] Examples 1 - 5, Comparative Examples 1 - 5 The compositions of the hemostatic compositions in the examples and comparative examples are shown in Tables 1 - 5. Specifically, the mass parts of the raw material components of the hemostatic composition are shown in Table 1. The mass parts of the raw material components of the tannic acid - modified carboxymethyl chitosan are shown in Table 2. The mass parts of the raw material components of the cross - linked starch are shown in Table 3. The mass parts of the raw material components of the carboxymethylated enzymatically hydrolyzed starch are shown in Table 4. The mass parts of the raw material components of the enzymatically hydrolyzed starch are shown in Table 5.

[0048] Table 1

[0049] Table 2

[0050] Table 3

[0051] Table 4

[0052] Table 5

[0053] Test Example (1)Hemostatic composition whole blood coagulation index (BCI) test: Add 10 mg of the composition powder sample to be tested to 200 μL of recalcified blood (10 μL of 0.2 mol / L calcium chloride per 100 μL of blood). After incubation with shaking (100 rpm) at 37 °C for 5 min, add 10 mL of deionized water to dissolve the uncoagulated blood clots. Measure the hemoglobin content of the supernatant at 540 nm using a microplate reader (Tecan, Switzerland). Calculation of the coagulation index (BCI): BCI (%) = (Is - I0) / (Ic - I0) × 100%, where Is represents the absorbance value of the sample, Ic represents the absorbance value of the positive control group (10 mL of deionized water directly dropped into 200 μL of recalcified blood), and I0 represents the absorbance value of the blank well plate. The test results are shown in Table 6.

[0054] (2)In vitro coagulation time test of the hemostatic composition: Add 5 mg of the composition powder sample to be tested to a centrifuge tube containing 100 μL of recalcified whole blood. Add 400 μL of PBS at a preset time and observe the diffusion behavior of the blood. The time when no blood diffuses into the PBS is defined as the coagulation time. The test results are shown in Table 6.

[0055] (3)Antibacterial performance test of the hemostatic composition: Select Escherichia coli (ATCC8739, Gram-negative bacteria) as the test strain to evaluate the antibacterial performance of the composition powder sample to be tested. Add 100 μL of a solution with a concentration of 107 CFU mL -1The Escherichia coli solution was dropped into the test composition powder gel and incubated at 37 °C for 2 h. 900 μL of PBS was added and thoroughly mixed. Subsequently, 10 μL of the solution was taken out, evenly spread on the pre-prepared agar plate, and incubated at 37 °C for 12 h. Finally, the number of bacterial colonies growing on the agar plate was observed and recorded. Similarly, 100 μL of the Escherichia coli solution with a concentration of 107 CFU mL -1 was incubated with the sample at 37 °C for 2 h, then 900 μL of Luria-Bertani (LB) broth was added to submerge the sample, and further incubated for 12 h. Finally, 200 μL of the bacterial suspension in each sample tube was transferred to a 96-well plate, and the absorbance value at 600 nm was measured using a microplate reader. Each group of experiments was repeated 3 times. The bactericidal rate was expressed as (ODc - ODs) / ODc × 100%, where ODs was the absorbance of the sample and ODc was the absorbance of the blank control without the sample. The test results are shown in Table 6.

[0056] (4) Characterization of the cytocompatibility of the hemostatic composition Each test composition powder was sterilized by ultraviolet light irradiation for 24 h before the experiment. PBS was dropped onto the test powder (the mass ratio of the sample powder to PBS was 1:3) to gel it, and a cylinder (with a diameter of 10 mm and a height of 2 mm) was prepared. After disinfecting with alcohol for 24 h, it was further soaked in the culture medium for 24 h to wash away the excess alcohol. L929 cells were inoculated at a density of 20,000 cells per well and cultured for 24 h and 48 h respectively. The live / dead staining method was used to evaluate cell viability, and observation and counting were carried out through an inverted fluorescence microscope (DMi1, Leica, Germany). The test results are shown in Table 6.

[0057] Table 6

[0058] As can be seen from Table 6, when cannabidiol, tannic acid-modified carboxymethyl chitosan, and cross-linked starch in the hemostatic composition are combined in a suitable mass ratio, the composition can have good hemostatic and antibacterial effects and good biocompatibility.

[0059] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

[0060] For those of ordinary skill in the art, according to the idea of the present invention, there will be changes in the specific implementation manners and application scopes. In summary, the content of this specification should not be construed as a limitation to the present invention.

Claims

1. A hemostatic composition, characterized in that, Its raw materials include the following components in parts by mass: 0.01 - 0.5 part of cannabidiol, 10 - 150 parts of tannic acid-modified carboxymethyl chitosan, and 5 - 250 parts of cross-linked starch; the raw materials of the tannic acid-modified carboxymethyl chitosan include the following components in parts by mass: 45 - 55 parts of carboxymethyl chitosan and 0.5 - 1.5 parts of tannic acid. The raw materials of the cross-linked starch include the following components in parts by mass: 95 - 105 parts of carboxymethyl hydrolyzed starch and 2 - 5 parts of sodium trimetaphosphate.

2. The hemostatic composition according to claim 1, wherein The raw materials of the carboxymethyl hydrolyzed starch include the following components in parts by mass: 22 - 30 parts of hydrolyzed starch and 15 - 20 parts of chloroacetic acid.

3. The hemostatic composition according to claim 2, wherein The raw materials of the hydrolyzed starch include the following components in parts by mass: 20 - 25 parts of potato starch, 0.2 - 0.5 part of glucoamylase, and 0.05 - 0.1 part of α-amylase.

4. The hemostatic composition according to claim 3, wherein, The mass ratio of the glucoamylase to the α-amylase is (2 - 5):1; the sum of the mass parts of the glucoamylase and the α-amylase is 0.25 - 0.5 part.

5. The hemostatic composition according to any one of claims 1-4, characterized in that, The raw materials of the hemostatic composition include the following components in parts by mass: 0.05 - 0.2 part of the cannabidiol, 50 - 100 parts of the tannic acid-modified carboxymethyl chitosan, and 50 - 150 parts of the cross-linked starch; the raw materials of the tannic acid-modified carboxymethyl chitosan include the following components in parts by mass: 48 - 52 parts of the carboxymethyl chitosan and 0.8 - 1.2 parts of the tannic acid; the raw materials of the cross-linked starch include the following components in parts by mass: 98 - 102 parts of carboxymethyl hydrolyzed starch and 2.5 - 4 parts of sodium trimetaphosphate; the raw materials of the carboxymethyl hydrolyzed starch include the following components in parts by mass: 24 - 28 parts of the hydrolyzed starch and 16 - 19 parts of chloroacetic acid; the raw materials of the hydrolyzed starch include the following components in parts by mass: 21 - 23 parts of the potato starch, 0.3 - 0.4 part of glucoamylase, and 0.06 - 0.09 part of α-amylase.

6. The hemostatic composition according to any one of claims 1-4, characterized in that, The raw materials of the hemostatic composition include the following components in parts by mass: 0.08 - 0.12 part of the cannabidiol, 70 - 80 parts of the tannic acid-modified carboxymethyl chitosan, and 60 - 100 parts of the cross-linked starch; the raw materials of the tannic acid-modified carboxymethyl chitosan include the following components in parts by mass: 50 parts of the carboxymethyl chitosan and 1 part of the tannic acid; the raw materials of the cross-linked starch include the following components in parts by mass: 100 parts of carboxymethyl hydrolyzed starch and 3 parts of sodium trimetaphosphate; the raw materials of the carboxymethyl hydrolyzed starch include the following components in parts by mass: 25 parts of the hydrolyzed starch and 18 parts of chloroacetic acid; the raw materials of the hydrolyzed starch include the following components in parts by mass: 21 parts of the potato starch, 0.32 part of glucoamylase, and 0.08 part of α-amylase.

7. A method for preparing the hemostatic composition according to any one of claims 1-6, characterized in that, It includes the following steps: preparing the tannic acid-modified carboxymethyl chitosan: dissolving the carboxymethyl chitosan in water to obtain an aqueous carboxymethyl chitosan solution, wherein the mass percentage of the carboxymethyl chitosan in the aqueous carboxymethyl chitosan solution is 2%-6%; dissolving the tannic acid in water to obtain an aqueous tannic acid solution, wherein the mass percentage of the tannic acid in the aqueous tannic acid solution is 2%-6%; slowly dropping the aqueous tannic acid solution into the aqueous carboxymethyl chitosan solution, reacting at 55-65°C for 2-4 h, maintaining the pH value of the reaction solution at 7-9 during the reaction process, introducing air during the reaction process, and the volume ratio of the aqueous tannic acid solution to the aqueous carboxymethyl chitosan solution is (45-55):1; after the reaction, subjecting the reaction solution to dialysis treatment and then freeze-drying to obtain the tannic acid-modified carboxymethyl chitosan; preparing the cross-linked starch: dissolving the carboxymethyl enzymatically hydrolyzed starch in water to obtain a carboxymethyl enzymatically hydrolyzed starch solution, adjusting the pH value of the carboxymethyl enzymatically hydrolyzed starch solution to 9.5-10.5, and then adding the sodium trimetaphosphate to form an aqueous phase; mixing the oil phase matrix and the emulsifier, wherein the mass percentage of the emulsifier in the oil phase matrix is 0.5%-2% to obtain an oil phase; dropping the aqueous phase into the oil phase and reacting at 55-65°C for 5-7 h; after the reaction, washing the reaction solution with a washing solution, the washing solution includes at least one of acetone, petroleum ether, aqueous sodium chloride solution and ethanol, and drying at 45-55°C after washing to obtain the cross-linked starch: preparing the hemostatic composition: adding the tannic acid-modified carboxymethyl chitosan and the cross-linked starch into the cannabidiol solution for mixing, the cannabidiol solution includes the cannabidiol, and then removing the solvent in the cannabidiol solution to obtain the hemostatic composition.

8. The preparation method of the hemostatic composition according to claim 7, wherein, The carboxymethyl enzymatic starch is prepared by the following method: Preparation of enzymatic starch: Dissolve potato starch in an acetic acid-sodium acetate buffer solution with a pH value of 3.5 - 4.5, then add glucoamylase and α-amylase, and react at 45 - 55 °C for 6 - 10 h. Among them, the mass parts of potato starch are 20 - 25 parts, the mass parts of glucoamylase are 0.2 - 0.5 parts, and the mass parts of α-amylase are 0.05 - 0.1 parts. The mass ratio of the glucoamylase to the α-amylase is (2 - 5):1, and the sum of the mass parts of the glucoamylase and the α-amylase is 0.25 - 0.

5. After the reaction, wash and filter the product, and vacuum-dry the solid-phase product at 45 - 55 °C to obtain enzymatic starch; Dissolve sodium hydroxide in an ethanol-aqueous solution to obtain a sodium hydroxide solution. The volume percentage of ethanol in the ethanol-aqueous solution is 90% - 95%, and in the sodium hydroxide solution, the mass percentage of sodium hydroxide is 2% - 4%; Add the enzymatic starch to the sodium hydroxide solution, and the mass of the enzymatic starch is equal to that of the sodium hydroxide; Carry out a reflux reaction at 45 - 55 °C for 25 - 35 min, then add chloroacetic acid to the reaction solution, and carry out a reflux reaction at 45 - 55 °C for 2 - 4 h. The mass parts of the enzymatic starch are 22 - 30 parts, and the mass parts of the chloroacetic acid are 15 - 20 parts; After the reaction, wash and filter the reaction product, and vacuum-dry the solid-phase product at 45 - 55 °C to obtain carboxymethyl enzymatic starch.

9. The preparation method of the hemostatic composition according to any one of claims 7-8, characterized in that, The dropping rate of slowly dropping the tannic acid aqueous solution into the carboxymethyl chitosan aqueous solution is 1 - 5 mL / min; The oil-phase matrix includes liquid paraffin; The emulsifier includes Span 80.

10. A hemostatic product, characterized in that, It includes the hemostatic composition according to any one of claims 1 - 6.

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