Rapid self-gelation modified gelatin-based styptic powder composition as well as preparation method and application thereof

Abstract

The invention relates to a rapid self-gelation modified gelatin-based styptic powder composition as well as a preparation method and application thereof. The styptic powder is composed of phenylboronic acid modified gelatin and a long-chain polymer containing a diol structure, and can be used independently or matched with thrombin or polyethylene glycol active derivative powder to prepare a composition for use. Under physiological conditions, the powder can rapidly absorb blood, settle and self-crosslink to form hydrogel, activate an endogenous hemostasis pathway and perform physical plugging, and rapid hemostasis is realized. When used together with thrombin, the medicine can maintain local high concentration and accelerate blood clot formation, and is suitable for emergency control of massive hemorrhage. When the hydrogel is combined with a polyethylene glycol active derivative, tissue adhesion and a dual-network structure can be realized, the gel strength is improved, and long-acting hemostasis is realized.

Description

Technical Field

[0001] The invention relates to the field of absorbable medical hemostatic materials, and in particular to a fast self-gelling modified gelatin-based hemostatic powder composition and a preparation method and application thereof. Background Art

[0002] In surgical operations, bleeding is an inevitable challenge, and failure to stop bleeding in time often leads to serious consequences or even death. Therefore, achieving rapid and effective hemostasis is a key link in medical treatment. At present, there are many types of hemostatic materials on the market, including hemostatic gauze, hemostatic sponges, hemostatic gels and hemostatic powders. Hemostatic gauze and hemostatic sponges mainly activate and accelerate the endogenous hemostasis process by absorbing blood and promoting blood concentration. Although these materials are easy to use, they usually require pressure to achieve hemostasis and are not suitable for wounds with complex shapes, large areas of bleeding or hidden bleeding points. Hemostatic gels block bleeding points by forming a physical barrier, but their use process is more complicated, sometimes requiring the mixing of multiple components, and most gels need to be converted from liquid to solid. In the face of wounds with continuous bleeding, the gel may be diluted by blood, thereby reducing its hemostatic effect. The working principle of hemostatic powder is similar to that of hemostatic gauze and sponges, and it also achieves hemostasis by promoting the endogenous hemostasis process. Hemostatic powder is portable and easy to use, and due to its large surface area and wide coverage, it can be applied to wounds with complex shapes, large bleeding areas, and situations with hidden bleeding points. However, existing hemostatic powder products still have some problems, such as slow liquid absorption rate, easy floating in blood, and insufficient in-situ adhesion.

[0003] Patent CN 116999607 discloses "a self-gelling rapid hemostatic powder, its preparation method and application". A new type of rapid hemostatic powder material is prepared by simply mixing chitosan derivatives and ionic crosslinking agent materials. After application, the chitosan derivatives and ionic crosslinking agents can quickly absorb the liquid components in the blood, and the chitosan derivatives and ionic crosslinking agents dissolve. The two form a stable three-dimensional hydrogel material through non-covalent interactions such as electrostatic interaction and hydrogen bonding, which forms a rapid physical blockage and hemostasis on the wound surface.

[0004] Patent CN 114767919 discloses "a kind of rapid hemostatic hydrogel powder and its preparation method and application". The main components include chitosan and polyacrylic acid. After the chitosan is dissolved, monomers, cross-linking agents, N-acryloxysuccinimide and photoinitiators are added. The polymerization reaction is carried out under ultraviolet light, and then the powder is dried and ground to obtain a rapid hemostatic hydrogel powder. After application, it can quickly absorb blood and quickly adhere to biological tissues, effectively solving the problems of poor adhesion of existing hemostatic materials and the need for pressing to assist hemostasis.

[0005] In summary, combining the advantages of hemostatic gel and hemostatic powder materials to develop a hemostatic powder material that can self-gel, absorb liquid quickly, settle quickly and adhere in situ has important research significance. Summary of the invention

[0006] The present invention aims to provide a rapid self-gelling gelatin-based hemostatic powder, comprising a complex of modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure. The present invention also provides a preparation method and an application method of a composition composed of the rapid self-gelling gelatin-based hemostatic powder and a supplementary hemostatic agent.

[0007] To achieve the above object, the technical solution adopted by the present invention is: A fast self-gelling modified gelatin-based hemostatic powder is characterized in that it is obtained by cross-linking modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure.

[0008] Furthermore, the modified gelatin is gelatin modified with phenylboronic acid, wherein the mass percentage of gelatin is 90-99% and the mass percentage of phenylboronic acid is 1-10%. Furthermore, the long-chain polymer containing 1,2-diol or 1,3-diol structure includes one or more of polyvinyl alcohol, carboxymethyl cellulose, dextran, etc., preferably, polyvinyl alcohol.

[0009] Furthermore, the mass ratio of the modified gelatin to the long-chain polymer containing 1,2-diol or 1,3-diol structure is 1:0.1-10.

[0010] A fast self-gelling gelatin-based hemostatic powder composition, characterized in that it comprises the fast self-gelling modified gelatin-based hemostatic powder according to claim 1 and a supplementary hemostatic agent, wherein the supplementary hemostatic agent includes thrombin or an active derivative of polyethylene glycol.

[0011] Furthermore, the thrombin in the composition includes one or more of human thrombin, porcine thrombin, and bovine thrombin, and is in the form of a powder, and the amount thereof ranges from 0.1 to 10 IU / mg of the composition.

[0012] Furthermore, the active derivatives of polyethylene glycol in the composition include one or more of succinimidyl carbonate-derived polyethylene glycol, succinimidyl acetate-derived polyethylene glycol, succinimidyl propionate-derived polyethylene glycol, succinimidyl succinate-derived polyethylene glycol, succinimidyl glutarate-derived polyethylene glycol, aldehyde-derived polyethylene glycol and succinimide-derived polyethylene glycol, and are in the form of powders, and the amount thereof ranges from 10 to 50% of the total mass of the composition.

[0013] The method for preparing the rapid self-gelling gelatin-based hemostatic powder composition comprises the following steps: (1) Prepare a gelatin aqueous solution with a concentration of 1-10 wt / v%, add gelatin powder to pure water containing buffer ions, stir and dissolve at 40-60°C, and maintain the pH value between 3 and 6; (2) preparing 1-20 wt / v% phenylboric acid (PBA) ethanol solution, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) ethanol solution and 1-30 wt / v% N-hydroxysuccinimide (NHS) ethanol solution; (3) Slowly drop the PBA solution prepared in step (2) into the gelatin solution prepared in step (1), stir for 10 to 90 min, then slowly drop the EDC solution and NHS solution in sequence, the mass ratio of PBA to gelatin is 1:1 to 10, the mass ratio of EDC to gelatin is 1:2 to 80, and the mass ratio of NHS to gelatin is 1:6 to 160. After all the additions are completed, adjust the pH to 5 to 6, continue to maintain the reaction at 30 to 38°C for 48 hours, and then dialyze, pre-freeze and freeze-dry to obtain phenylboronic acid modified gelatin; (4) preparing a 1-10 wt / v% aqueous solution of phenylboronic acid-modified gelatin as reaction solution A. preparing a 1-10 wt / v% aqueous solution of a long-chain polymer containing a 1,2-diol or 1,3-diol structure as reaction solution B, mixing reaction solutions A and B in a volume ratio of 1:0.1-10, and pre-freezing and freeze-drying after they are completely gelled; (5) The product obtained in step (4) is mechanically crushed and sieved to obtain particles in the target particle size range (50-300 mesh), which can be used alone or physically mixed with thrombin or polyethylene glycol active derivative powder for uniform use.

[0014] Furthermore, the phenylboronic acid in step (2) includes one or more of 3-aminophenylboronic acid, 3-carboxyphenylboronic acid and 4-carboxyphenylboronic acid, and preferably 3-aminophenylboronic acid or 3-carboxyphenylboronic acid.

[0015] Furthermore, the phenylboric acid modified gelatin aqueous solution in step (4) may be added with one or more inorganic salts including sodium chloride, potassium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, borax, etc., or may not be added.

[0016] Furthermore, the composition may be added with monosaccharides as excipients, and the monosaccharides include one or more of glucose, mannitol, sucrose, and fructose.

[0017] Furthermore, the mass range of the added monosaccharide is 0.1-10% of the total mass of the composition.

[0018] Furthermore, the composition can be physically mixed with glycosaminoglycans to improve the liquid absorption ratio and liquid absorption rate. The glycosaminoglycans include one or more of chondroitin sulfate, dermatan sulfate, and hyaluronic acid, preferably chondroitin sulfate.

[0019] Furthermore, the mass range of the added glycosaminoglycan is 1-20% of the total mass of the composition.

[0020] A fast self-gelling modified gelatin-based hemostatic powder and its application in combination, the hemostatic powder is provided in the form of dry powder, characterized in that: the particle size range is 50 to 300 mesh; the hemostatic powder is filled into a powder sprayer; the hemostatic powder is sterilized by γ irradiation, and the sterilization dose is 25 to 40 kGy; the hemostatic powder includes any of the following forms: a. A single composite powder of phenylboronic acid modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure; b. A composition of a composite powder of phenylboronic acid modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure mixed with thrombin powder; c. A composition of a composite powder of phenylboronic acid modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure mixed with a polyethylene glycol active derivative powder.

[0021] The beneficial effects of the present invention are: The phenylboronic acid modified gelatin-based composite powder of the present invention can quickly absorb blood, settle and trigger a self-crosslinking reaction under physiological conditions, and form a hydrogel in situ through the rapid reconstruction of borate bonds between the particles, and achieve rapid hemostasis by activating and accelerating the endogenous hemostatic pathway and the physical blocking of the gel. In addition, the formed hydrogel has good plasticity and a stable swelling ratio, can better adapt to the shape of the wound, and has no risk of squeezing the surrounding tissue due to excessive swelling.

[0022] The phenylboronic acid modified gelatin-based composite powder of the present invention can achieve a better hemostatic effect by synergistic use with a supplementary hemostatic agent. When used in combination with thrombin, the rapid liquid absorption and self-gelation ability of the composite powder can ensure a high local concentration of thrombin, thereby accelerating the formation of blood clots, and is particularly suitable for emergency control of massive bleeding; when used in combination with an active derivative of polyethylene glycol, the active ester bond can undergo a spontaneous amidation reaction with the amino group on the tissue surface and the gelatin molecular chain, thereby achieving stable tissue adhesion, and at the same time, a double network structure can be formed inside the gel to enhance the overall strength and achieve long-term hemostasis. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Attached Figure 1 The following are pictures of the self-gelation of the phenylboronic acid-modified gelatin-based composite powders prepared in Examples 1 and 2 after absorbing water.

[0024] Attached Figure 2This is a picture showing the self-gelation and tissue adhesion of the phenylboronic acid modified gelatin-based composition powder prepared in Example 4 after absorbing water.

[0025] Attached Figure 3 These are pictures of the in vitro coagulation test of the samples of Example 1 and Comparative Example 1. DETAILED DESCRIPTION

[0026] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. It should be understood by those skilled in the art that the following specific description is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0027] Example 1 (1) Prepare a 4 wt / v% gelatin aqueous solution and stir it continuously at 55 °C until the gelatin is completely dissolved. The solvent used is phosphate buffer with a pH of 4.5 and a concentration of 0.1 M.

[0028] (2) Prepare a 10 wt / v% ethanol solution of 3-carboxyphenylboronic acid, a 10 wt / v% ethanol solution of EDC, and a 4 wt / v% ethanol solution of NHS.

[0029] (3) Slowly drop the 3-carboxyphenylboronic acid solution prepared in step (2) into the gelatin solution prepared in step (1), stir for 20 min, then slowly drop the EDC solution and NHS solution in sequence, the mass ratio of 3-carboxyphenylboronic acid to gelatin is 1:2, the mass ratio of EDC to gelatin is 1:4, and the mass ratio of NHS to gelatin is 1:7. After all the additions are completed, adjust the pH to 5-6 with 1 M NaOH solution, keep the temperature at 30-38°C for 48 h, and then dialyze, pre-freeze and freeze-dry to obtain 3-carboxyphenylboronic acid modified gelatin.

[0030] (4) A 4 wt / v% aqueous solution of 3-carboxyphenylboronic acid-modified gelatin was prepared as reaction solution A; a 2 wt / v% aqueous solution of polyvinyl alcohol was prepared as reaction solution B. Reaction solutions A and B were mixed in a volume ratio of 1:1, and after they were completely gelled, they were pre-frozen and freeze-dried.

[0031] (5) The product obtained in step (4) is mechanically crushed and sieved to obtain particles with a target particle size range (50-300 mesh), namely, phenylboronic acid modified gelatin-based composite powder particles. Example 2

[0032] (1) Prepare a 4 wt / v% gelatin aqueous solution and stir it continuously at 55 °C until the gelatin is completely dissolved. The solvent used is phosphate buffer with a pH of 4.5 and a concentration of 0.1 M.

[0033] (2) Prepare a 10 wt / v% ethanol solution of 3-aminophenylboronic acid, a 10 wt / v% ethanol solution of EDC, and a 4 wt / v% ethanol solution of NHS.

[0034] (3) Slowly drop the 3-aminophenylboronic acid solution prepared in step (2) into the gelatin solution prepared in step (1). After stirring for 20 min, slowly drop the EDC solution and NHS solution in sequence. The mass ratio of 3-aminophenylboronic acid to gelatin is 1:2.7, the mass ratio of EDC to gelatin is 1:4, and the mass ratio of NHS to gelatin is 1:7. After all the additions are completed, add 10-fold diluted H 3 PO 4 The pH value was adjusted to 5-6, and the reaction was maintained at 30-38°C for 48 hours. After completion, the reaction was performed by dialysis, pre-freezing and freeze-drying to obtain 3-aminophenylboronic acid modified gelatin.

[0035] (4) A 5 wt / v% aqueous solution of 3-aminophenylboronic acid-modified gelatin was prepared as reaction solution A; a 2.5 wt / v% aqueous solution of polyvinyl alcohol was prepared as reaction solution B. Reaction solutions A and B were mixed in a volume ratio of 1:1, and after they were completely gelled, they were pre-frozen and freeze-dried.

[0036] (5) The product obtained in step (4) is mechanically crushed and sieved to obtain particles with a target particle size range (50-300 mesh), namely, phenylboronic acid modified gelatin-based composite powder particles.

[0037] Example 3 According to step (1) to step (3) in Example 2, 3-aminophenylboronic acid modified gelatin was prepared, and the feeding parameters of 3-aminophenylboronic acid were adjusted to investigate its effect on the grafting amount. The proportions of all groups were as follows: Group 1 Group 2 Group 3 Group 4 3-Aminophenylboronic acid: Gelatin 1:2.7 1:2 1:1.3 1:1 Group 1 is the preparation parameters of 3-aminophenylboronic acid modified gelatin in Example 2.

[0038] 3-Aminophenylboronic acid-modified gelatin was dissolved in pure water at a concentration of 3 mg / mL. The absorbance of the solution at 270 nm was measured by an ultraviolet spectrophotometer, and the phenylboronic acid content in the gelatin was calculated using the calibration curve.

[0039] For the calibration curve, 3-aminophenylboronic acid solutions were prepared with concentrations of 0.005, 0.01, 0.02, 0.05, and 0.1 mg / mL, respectively.

[0040] The test results of the standard solution are as follows 3-Aminophenylboronic acid concentration (mg / mL) Absorbance (270 nm) 0.005 0.1643 0.01 0.3254 0.02 0.6477 0.05 1.5855 0.1 2.8539 The linear relationship after fitting is Y=0.0351X - 0.0022; R 2 =0.9969 The X-axis is the absorbance at 270 nm; the Y-axis is the concentration of 3-aminophenylboronic acid.

[0041] The phenylboronic acid branch content of all groups was expressed as a percentage of the total mass of modified gelatin. The results are shown in Table 1.

[0042] Table 1. Dopamine grafting amount in modified gelatin Group Group 1 Group 2 Group 3 Group 4 Grafting amount 1.72% 2% 2.04% 1.95% From the above results, it can be seen that increasing the dosage of phenylboric acid within a certain range can increase the grafting amount. Taking all factors into consideration, the dosage of Group 2 is the best. Example 4

[0043] Provided is a fast self-gelling modified gelatin-based hemostatic powder composition, comprising the following components: (1) the phenylboronic acid modified gelatin-based composite powder particles prepared in Example 1; (2) Four-arm succinimidyl glutarate polyethylene glycol derivative powder particles with a molecular weight of 20 kDa.

[0044] The mass ratio of component (1) to component (2) is 7:3. Example 5

[0045] Provided is a fast self-gelling modified gelatin-based hemostatic powder composition, comprising the following components: (1) phenylboronic acid modified gelatin-based composite powder particles prepared in Example 2; (2) lyophilized thrombin powder particles; (3) Chondroitin sulfate; (4) Glucose.

[0046] The mass ratio of component (1) to component (3) and component (4) is 20:3:1, and the dosage of component (2) is 1 IU / mg. Example 6

[0047] 2 g of the composition powder in Example 5 was filled into a powder sprayer and sterilized by gamma irradiation after packaging with an irradiation dose of 25 kGy to obtain a fast self-gelling modified gelatin-based hemostatic powder composition product suitable for direct injection applications.

[0048] Comparative Example 1 (1) Prepare a 4 wt / v% gelatin aqueous solution and stir continuously at 55 °C until it is completely dissolved.

[0049] (2) Prepare a 2 wt / v% polyvinyl alcohol solution and continue stirring at 80 °C until it is completely dissolved.

[0050] (3) The gelatin solution and the polyvinyl alcohol solution are mixed in a volume ratio of 1:1, followed by pre-freezing and freeze-drying.

[0051] (4) The product obtained in step (3) is mechanically crushed and sieved to obtain particles with a target particle size range (50-300 mesh). Powder self-gelation and self-healing test

[0052] The sample powders in Example 1 and Example 2 were naturally sprinkled into 0.01 M PBS (pH 7.4) at a mass-to-volume ratio of 1:10, and the time required for gelation was recorded. After the gel was taken out, it was cut open and then spliced ​​together to observe whether the gel could heal itself.

[0053] The time required for the sample powder to self-gel is shown in Table 2 and the pictures are shown in the attached Figure 1 .

[0054] Table 2. Powder self-gelation time Group Example 1 Example 2 Self-gel time 2 s 2 s From the above results, it can be seen that the phenylboronic acid modified gelatin-based composite powder particles have extremely fast liquid absorption and self-gelation rates. After the powder particles are sprinkled into the PBS solution, they absorb liquid almost instantly and form gel simultaneously through the reconstruction of the borate ester bonds. At the same time, the gel also has rapid self-healing ability, which also means that it has good plasticity and can better adapt to the shape of the wound.

[0055] In addition, the self-gelation speed and self-healing performance of the samples in Example 1 and Example 2 are similar, indicating that the modified gelatin modified with 3-aminophenylboronic acid or 3-carboxyphenylboronic acid has similar performance. Gel swelling ratio test

[0056] Use the sample test in Example 1 and weigh the powder mass, calculated as m 0 , sprinkled naturally into 0.01 M PBS (pH 7.4) at a mass-to-volume ratio of 1:10, and weighed after gelation, which was calculated as m 1 , initial swelling ratio = m 1 / m 0 Then, the gel was soaked in 0.01 M PBS (pH 7.4) and placed at 37 °C for 8 h and 24 h before being taken out and weighed respectively, which was calculated as m 2 and m 3 , if m 3 / m 0 With m 2 / m 0If the difference does not exceed 10%, it is judged that the swelling has reached equilibrium. The results are shown in Table 3.

[0057] Table 3. Changes in swelling ratio of hydrogels time 0 h 8 h 24 h Swelling ratio 9.5 6.1 6.3 From the above results, it can be seen that the initial swelling ratio of the phenylboronic acid-modified gelatin-based composite powder is about 10, and the formed hydrogel can reach swelling equilibrium within 24 hours with a swelling ratio of about 6, without the risk of continuous swelling and compression of surrounding tissues. Tissue Adhesion Test

[0058] The sample powder of the composition in Example 4 was sprinkled on the surface of bovine pericardium tissue, and 0.01 M PBS (pH 7.4) was added to dissolve the gel. Stretching, bending, twisting and other forces were applied to the bovine pericardium to observe its adhesion. The results are shown in the attached Figure 2 .

[0059] After adding PBS, the sample powder of the composition quickly absorbed liquid and gelled. At the same time, the active derivatives of polyethylene glycol can undergo spontaneous amidation reaction with the amino groups on the surface of the bovine pericardium and the amino groups on the gelatin molecular chain in the composition, thereby adhering in situ. When the bovine pericardium tissue is lifted vertically, it can be seen that the gel has completed adhesion. After applying external forces such as stretching, bending, and twisting to it, the gel still adheres. It can be seen that the combination of phenylboronic acid modified gelatin-based composite powder and active derivatives of polyethylene glycol can make it have good tissue adhesion. In vitro coagulation test

[0060] Take fresh rabbit blood into a sodium citrate blood collection tube and add 1 / 4 of the rabbit blood volume of CaCl 2 Solution (0.2 M) was added to neutralize the anticoagulant in the blood. The sample powder in Example 1 was naturally sprinkled in at a mass volume ratio of 1:6, 1:8, and 1:10, respectively, and the gelation time was recorded. The sample powder in Comparative Example 1 was naturally sprinkled in at a mass volume ratio of 1:10, and the gelation time was recorded as Group D. The results are shown in Table 4 and Figure 3 .

[0061] Table 4. Powder self-gelation time Group A B C D Self-gel time 3 s 3 s 3 s Powder not wetted after 5 min The above-mentioned Group D is a powder obtained by simply physically mixing gelatin and polyvinyl alcohol solution and then processing. After contacting with blood for 5 minutes, it still basically floats above the blood and the blood has not coagulated. This shows that the gelatin / polyvinyl alcohol powder that has not been modified or processed does not have a good blood absorption capacity. The present invention uses phenylboric acid to modify the gelatin, and after forming a gel with the polyvinyl alcohol molecules through borate bonds, the powder particles obtained by freeze-drying and grinding can quickly absorb blood, settle and form a gel, and its hemostatic performance is greatly improved.

[0062] The gels in groups A, B, and C were taken out and weighed, and then the gels were immersed in 0.01 M PBS (pH 7.4) and placed at 37°C for 8 h and 24 h, and then taken out. The swelling ratios at the three moments were calculated, respectively, as shown in Table 5.

[0063] Table 5. Changes in the swelling ratio of the gel Time Group 0 h 8 h 24 h A 6.3 8.1 6.1 B 8.1 8.5 5.9 C 8.3 8.8 6.2 From the above results, it can be seen that the initial swelling ratio of the phenylboronic acid modified gelatin-based composite powder after mixing with blood is about 8, and the formed gel can reach swelling equilibrium within 24 hours, with a swelling ratio of about 6, which is close to the performance of the gel formed by mixing with PBS, indicating that the composite powder can still stabilize its swelling ratio in practical applications.

Claims

1. A fast self-gelling modified gelatin-based hemostatic powder, characterized in that The modified gelatin is obtained by cross-linking a modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure; wherein the modified gelatin is gelatin modified with phenylboronic acid, wherein the mass percentage of gelatin is 90-99%, and the mass percentage of phenylboronic acid is 1-10%; and the long-chain polymer containing a 1,2-diol or 1,3-diol structure comprises one or more of polyvinyl alcohol, carboxymethyl cellulose and dextran.

2. The fast self-gelling modified gelatin-based hemostatic powder according to claim 1, characterized in that: The mass ratio of the modified gelatin to the long-chain polymer containing 1,2-diol or 1,3-diol structure is 1:0.1-10.

3. A fast self-gelling modified gelatin-based hemostatic powder composition, characterized in that It comprises the fast self-gelling modified gelatin-based hemostatic powder as described in claim 1 and a supplementary hemostatic agent; the supplementary hemostatic agent includes thrombin or an active derivative of polyethylene glycol; the thrombin includes one or more of human thrombin, porcine thrombin, and bovine thrombin, and is in the form of a powder, and its amount ranges from 0.1 to 10 IU / mg of the composition; the active derivative of polyethylene glycol includes one or more of succinimidyl carbonate-derived polyethylene glycol, succinimidyl acetate-derived polyethylene glycol, succinimidyl propionate-derived polyethylene glycol, succinimidyl succinate-derived polyethylene glycol, succinimidyl glutarate-derived polyethylene glycol, aldehyde-derived polyethylene glycol, and succinimide-derived polyethylene glycol, and is in the form of a powder, and its amount ranges from 10 to 50% of the total mass of the composition.

4. The method for preparing a fast self-gelling modified gelatin-based hemostatic powder composition according to claim 1, characterized in that: The following steps are involved: (1) Prepare a gelatin aqueous solution with a concentration of 1-10 wt / v%, add gelatin powder to pure water containing buffer ions, stir and dissolve at 40-60°C, and maintain the pH value between 3 and 6; (2) preparing 1-20 wt / v% phenylboric acid (PBA) ethanol solution, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) ethanol solution and 1-30 wt / v% N-hydroxysuccinimide (NHS) ethanol solution; (3) slowly dropwise adding the PBA solution prepared in step (2) to the gelatin solution prepared in step (1), stirring for 10 to 90 minutes, and then slowly dropwise adding the EDC solution and the NHS solution in sequence, wherein the mass ratio of PBA to gelatin is 1:1 to 10, the mass ratio of EDC to gelatin is 1:2 to 80, and the mass ratio of NHS to gelatin is 1:6 to 160. After all the dropwise additions are completed, the pH is adjusted to 5 to 6, and the reaction is continued at 30 to 38° C. for 48 hours. After completion, dialyzing, pre-freezing and freeze-drying are performed to obtain phenylboronic acid modified gelatin; (4) preparing a 1-10 wt / v% phenylboronic acid modified gelatin aqueous solution as reaction solution A; preparing a 1-10 wt / v% long chain polymer aqueous solution containing 1,2-diol or 1,3-diol structure as reaction solution B; mixing reaction solutions A and B in a volume ratio of 1:0.1-10, and pre-freezing and freeze-drying after they are completely gelled; (5) The product obtained in step (4) is mechanically crushed and sieved to obtain particles in the target particle size range (50-300 mesh), which can be used alone or physically mixed with thrombin or polyethylene glycol active derivative powder for uniform use.

5. The preparation method according to claim 5, characterized in that: The phenylboronic acid includes one or more of 3-aminophenylboronic acid, 3-carboxyphenylboronic acid and 4-carboxyphenylboronic acid.

6. The preparation method according to claim 5, characterized in that: The phenylboric acid modified gelatin aqueous solution may be added with one or more of sodium chloride, potassium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, and borax, or may not be added.

7. The composition according to claim 4, characterized in that Monosaccharides and / or glycosaminoglycans may be added to the composition, wherein the monosaccharides include one or more of glucose, mannitol, sucrose, and fructose, and the mass range of the added monosaccharides is 1-10% of the total mass of the composition; the glycosaminoglycans include one or more of chondroitin sulfate, dermatan sulfate, and hyaluronic acid, and the mass range of the added glycosaminoglycans is 1-20% of the total mass of the composition.

8. The use of a fast self-gelling modified gelatin-based hemostatic powder and a composition thereof according to claims 1 to 7, wherein the hemostatic powder is provided in the form of a dry powder, characterized in that: The particle size range is 50 to 300 mesh; the hemostatic powder is filled into a powder sprayer; the hemostatic powder is sterilized by γ irradiation, and the sterilization dose is 25 to 40 kGy; the hemostatic powder includes any of the following forms: a. A single complex powder of phenylboronic acid modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure; b. A composition in which the complex powder of phenylboronic acid modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure is mixed with thrombin powder; c. A composition in which the complex powder of phenylboronic acid modified gelatin and a long-chain polymer containing a 1,2-diol or 1,3-diol structure is mixed with polyethylene glycol active derivative powder.

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