Hemostatic powder for rapid hemostasis of traumatic bleeding, preparation method therefor and use thereof

Abstract

A hemostatic powder for rapid hemostasis of traumatic bleeding, a preparation method therefor and the use thereof. The hemostatic powder comprises: sodium alginate, CaCl2 and Ce(NO3)3•6H2O. The hemostatic powder can absorb water and undergo a cross-linking reaction to form a hydrogel in situ on wound surfaces, so as to form a hyperbranched network structure. The hemostatic powder has good water absorption capacity and mechanical properties, and thus has good clinical application and translational potentials in the aspect of prehospital rapid hemostasis.

Description

Hemostatic powder for rapid hemostasis of traumatic massive bleeding, preparation method and application thereof TECHNICAL FIELD

[0001] The present application relates to the technical field of hemostatic materials, in particular to a hemostatic powder for rapid hemostasis of traumatic massive bleeding, a preparation method and application thereof. BACKGROUND

[0002] Traumatic massive bleeding is one of the main causes of shock and death, especially in accidental accidents such as car accidents, natural disasters, etc. The total amount of human blood is relatively constant, and once it is excessively reduced, multiple complications will be rapidly caused, and in severe cases, death can be caused. Statistical data shows that in accidental accidents, the death rate of massive bleeding accounts for as high as 39%, and in the battlefield, the mortality rate caused by uncontrollable bleeding is more than 85%. Studies have shown that about 2.5% of deaths can be avoided by taking hemostatic drugs or interventional treatment at the initial stage of uncontrollable bleeding.

[0003] Rapid hemostasis can improve the survival rate of the wounded in first aid, especially pre-hospital first aid. Pre-hospital first aid is usually the first aid method of the wounded before receiving professional medical equipment diagnosis and treatment due to accidents.

[0004] At present, the commonly used hemostatic materials in clinical practice, such as Merocel, Ivalon, etc., are mainly suitable for hemostasis in daily operations, but the hemostatic effect is not ideal for the hemostasis of large artery jet-like bleeding. These materials are often expensive, and most of them depend on imports, and there is a blank in this field in the domestic market. In addition, the US military has equipped rapid hemostatic materials for arterial bleeding in the Iraq War in 2003, and further developed advanced military equipment that can rapidly hemostasis in 2007, while China is still in the initial stage of research and development of such products.

[0005] In summary, the development of rapid hemostatic materials and related products for wound hemostasis and emergency care has always been a hot spot of research at home and abroad. Hemostasis is an important technical problem for military and civilian trauma centers around the world. SUMMARY

[0006] The purpose of the present application is to develop a new, effective, and reasonably priced rapid hemostatic material to meet the needs of pre-hospital first aid and battlefield first aid. This material should be able to quickly control massive bleeding and improve the survival rate of the wounded, especially before emergency care arrives.

[0007] In order to achieve the above purpose, the present application provides a hemostatic powder for rapid hemostasis of traumatic massive bleeding, comprising: sodium alginate, CaCl2 and Ce(NO3)3·6H2O.

[0008] Optionally, the mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O is (5-20):1:(1-2).

[0009] Optionally, the mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O is 10:1:1.

[0010] Optionally, the hemostatic powder further comprises: graphene oxide.

[0011] Optionally, the mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O: graphene oxide is (5-20):1:(1-2):(0.1-0.5).

[0012] Optionally, the mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O: graphene oxide is 10:1:1:(0.1-0.5).

[0013] Optionally, the mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O: graphene oxide is 10:1:1:0.3.

[0014] The application also provides a preparation method of the hemostatic powder for rapid hemostasis of traumatic hemorrhage, comprising the following steps:

[0015] Step S1, grinding calcium chloride anhydrous particles into calcium chloride anhydrous powder, the powder particle size range is 1μm-50μm.

[0016] Step S2, uniformly mixing the calcium chloride anhydrous powder with sodium alginate and Ce(NO3)3·6H2O by ball milling, the powder particle size range is 1μm-50μm.

[0017] Optionally, the step S2 further adds graphene oxide.

[0018] The application also provides a use of the hemostatic powder for rapid hemostasis of traumatic hemorrhage, and the hemostatic powder is used for emergency pre-hospital hemostasis of traumatic massive hemorrhage.

[0019] Compared with the prior art, the technical scheme of the application has at least the following beneficial effects:

[0020] 1) The hemostatic powder prepared by the present application can concentrate platelets and preliminarily promote blood coagulation by means of the water absorption and viscosity of sodium alginate; the calcium ions released after the water absorption of calcium chloride powder can be coordinated with sodium alginate to trigger the formation of hydrogel. Further, the calcium ions released by the hemostatic powder of the present application can activate coagulation factors and promote the formation of a complex of tissue factor and coagulation factor to form fibrin, enhance platelet embolism, and promote the formation of stable blood clots.

[0021] 2) Further, based on the high coordination coefficient characteristics of cerium ions, the present application uses the coordination of cerium ions to crosslink carboxylated graphene oxide and sodium alginate to form a dense network structure, increase the viscosity and mechanical strength of the hemostatic powder after water absorption to form a gel, and more easily adhere to the surface of the wound to resist blood flow flushing.

[0022] 3) The main raw material of the hemostatic powder of the present application is derived from natural biological products, is easy to degrade, does not cause large resource waste, is environmentally friendly, and the preparation method is simple and easy to control. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 is a schematic diagram of the water absorption rate comparison results in Example 12.

[0024] Figure 2 is a schematic diagram of the water absorption comparison results of SA-CC (10:1:1) and SA-CCG (10:1:1:0.3).

[0025] Figure 3 is a schematic diagram of the stress-strain test comparison results in Example 13.

[0026] Figure 4 is a schematic diagram of the compression modulus comparison results in Example 13.

[0027] Figure 5 is a schematic diagram of the scanning electron microscope comparison of SA-CC and SA-CCG in Example 14. Wherein, A is the gel formed by SA-CC (10:1:1) magnified 2000 times, B is the gel formed by SA-CC (10:1:1) magnified 500 times, C is the gel formed by SA-CCG (10:1:1:0.3) magnified 2000 times, and D is the gel formed by SA-CCG (10:1:1:0.3) magnified 500 times.

[0028] Figure 6 is a schematic diagram of the in vitro coagulation effect comparison in Example 15.

[0029] Figure 7 is a schematic diagram of the cell survival rate comparison of fibroblasts after co-incubation with different concentrations of SA-CCG for 24 h in Example 16.

[0030] Figure 8 is a schematic diagram of the hemostatic effect of SA-CCG in a rat liver injury model in Example 17. Wherein, A is a schematic diagram of bleeding after liver injury, B is a comparison diagram of hemostatic time, C is a comparison diagram of bleeding volume, and D is a comparison diagram of coagulation at different times.

[0031] Figure 9 is a diagram of the hemostatic effect of the SA-CCG rat tail amputation model in Example 18, wherein A is a diagram of the bleeding of the tail amputation model, B is a comparison diagram of the hemostatic time, C is a comparison diagram of the bleeding amount, and D is a comparison diagram of the coagulation at different times. DETAILED DESCRIPTION

[0032] The technical solutions of the present application will be described clearly and completely below in conjunction with the drawings. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0033] The hemostatic powder uses a large amount of liquid in the bleeding environment as a trigger for the transition of the hemostatic material from a powder state to a gel state. Compared with other existing hemostatic powders, the hemostatic powder prepared in the present application uses a bimetallic ion crosslinking agent Ca 2+ , Ce 3+ and sodium alginate to form a gel, and uses the strong coordination characteristics of Ce 3+ to crosslink sodium alginate and graphene oxide to form a hyperbranched network structure, further improving the viscosity and mechanical properties of the gel, and having better clinical application and transformation potential.

[0034] The hemostatic powder prepared in the present application has innovation in the strategy of rapid gel formation to plug the bleeding site, which uses a large amount of liquid in the bleeding environment as a switch to trigger a high-viscosity, high-mechanical-strength gel to plug the blood vessel bleeding, and proposes a “three-step synergy” strategy: first, by virtue of the water absorption and viscosity of sodium alginate in the hemostatic powder components, platelets are preliminarily activated to promote coagulation, and the first “defense line” of hemostasis is constructed; second, the calcium ions released after the water absorption of calcium chloride powder in the hemostatic powder can be coordinated with sodium alginate to trigger the formation of a hydrogel, and the released calcium ions can also start the in vivo hemostatic biochemical program to induce platelet activation, thereby promoting rapid coagulation of the wound and further strengthening the “defense line”; finally, based on the “lanthanide contraction” theory and the high coordination coefficient characteristics of cerium ions, the important components of the hemostatic powder, carboxylated graphene oxide and sodium alginate, are crosslinked by coordination to form a dense network structure, thereby improving the viscosity and mechanical properties of the hemostatic gel and strengthening the “defense line” of hemostasis.

[0035] The present application provides a kind of hemostatic powder for traumatic bleeding rapid hemostasis, comprising: sodium alginate, CaCl2 And Ce (NO3) 3 ·6H2O. Optionally, sodium alginate: CaCl2 : Ce (NO3) 3 ·6H2O is (5~20) by mass ratio: 1: (1~2).

[0036] Further, the application further provides a hemostatic powder for rapid hemostasis of traumatic hemorrhage, comprising: sodium alginate, CaCl2 and Ce(NO3)3·6H2O and graphene oxide. Optionally, the mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O: graphene oxide is (5-20):1:(1-2):(0.1-0.5). Optionally, the mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O: graphene oxide is 10:1:1:(0.1-0.5).

[0037] The application provides a preparation method of an organic-inorganic hybrid rapid hemostatic powder, comprising the following steps:

[0038] (1) The anhydrous calcium chloride (CaCl2) particle is ball milled into a uniform fine powder, and the powder particle size ranges from 1 μm to 50 μm;

[0039] (2) The anhydrous calcium chloride (CaCl2) powder obtained in step (1) is uniformly mixed with sodium alginate (SA) and cerium nitrate hexahydrate (Ce(NO3)3·6H2O) by ball milling to obtain (SA-CC), and the powder particle size ranges from 1 μm to 50 μm;

[0040] (3) The anhydrous calcium chloride (CaCl2) powder obtained in step (1) is uniformly mixed with sodium alginate (SA), cerium nitrate hexahydrate (Ce(NO3)3·6H2O) and graphene oxide (GO) by ball milling to obtain (SA-CCG), and the powder particle size ranges from 1 μm to 50 μm.

[0041] In an embodiment of the application, the sodium alginate powder, the anhydrous calcium chloride particle and the cerium nitrate hexahydrate particle are weighed according to a certain proportion and placed in a ball milling tank.

[0042] In an embodiment of the application, the ball milling parameters are controlled as follows: 8 medium balls and 8 small balls at 180 rpm, and the balls are milled for 20 minutes.

[0043] In an embodiment of the application, before ball milling, the ball milling tank is protected by nitrogen for 5 minutes.

[0044] The application provides an application of the organic-inorganic hybrid rapid hemostatic powder in emergency treatment of traumatic massive hemorrhage caused by war or accidental disaster, which can realize emergency pre-hospital hemostasis.

[0045] The application will be described in detail below in combination with the drawings and specific embodiments.

[0046] In the following examples, if not specifically stated, the reagents used are all commercially available reagents; and the detection methods and means are all conventional detection methods and means in the field. Example 1

[0047] The embodiment provides a preparation method of anhydrous calcium chloride powder.

[0048] 1g of CaCl2 is weighed and placed in a ball mill tank, and ball milling parameters are 180 rpm, 8 medium balls and 8 small balls, and 20 minutes. Example 2

[0049] The embodiment provides a preparation method of SA-C (10:1).

[0050] Sodium alginate powder and anhydrous calcium chloride particles are weighed according to a certain mass ratio and placed in a ball mill tank. Ball milling parameters are controlled to be 180 rpm, 8 medium balls and 8 small balls, and 20 minutes, so that SA-C hemostatic powder uniformly mixed is obtained.

[0051] The raw material of the application is used in an amount of: 100 mg of sodium alginate, 20 mg of anhydrous calcium chloride powder. Example 3

[0052] The embodiment provides a preparation method of SA-CC (5:1:1).

[0053] Sodium alginate powder, anhydrous calcium chloride particles and cerium nitrate hexahydrate particles are weighed according to a certain mass ratio and placed in a ball mill tank. Ball milling parameters are controlled to be 180 rpm, 8 medium balls and 8 small balls, and 20 minutes, so that SA-CC hemostatic powder uniformly mixed is obtained.

[0054] The raw material of the application is used in an amount of: 100 mg of sodium alginate, 20 mg of anhydrous calcium chloride powder and 26.2 mg of cerium nitrate hexahydrate. Example 4

[0055] The embodiment provides a preparation method of SA-CC (10:1:1).

[0056] Sodium alginate powder, anhydrous calcium chloride particles and cerium nitrate hexahydrate particles are weighed according to a certain mass ratio and placed in a ball mill tank. Ball milling parameters are controlled to be 180 rpm, 8 medium balls and 8 small balls, and 20 minutes, so that SA-CC hemostatic powder uniformly mixed is obtained.

[0057] The raw material of the application is used in an amount of: 100 mg of sodium alginate, 10 mg of anhydrous calcium chloride powder and 13.1 mg of cerium nitrate hexahydrate. Example 5

[0058] The embodiment provides a preparation method of SA-CC (15:1:1).

[0059] Sodium alginate powder, calcium chloride anhydrous particles and cerium nitrate hexahydrate particles were weighed according to a certain mass ratio and placed in a ball mill jar. The ball milling parameters were controlled as 180 rpm, 8 medium balls and 8 small balls, and 20 minutes. Thus, the SA-CC hemostatic powder uniformly mixed was obtained.

[0060] The raw material usage of the present application is: sodium alginate 150 mg, calcium chloride anhydrous powder 10 mg, and cerium nitrate hexahydrate 13.1 mg. Example 6

[0061] The present embodiment provides a preparation method of SA-CC (20:1:1).

[0062] Sodium alginate powder, calcium chloride anhydrous particles and cerium nitrate hexahydrate particles were weighed according to a certain mass ratio and placed in a ball mill jar. The ball milling parameters were controlled as 180 rpm, 8 medium balls and 8 small balls, and 20 minutes. Thus, the SA-CC hemostatic powder uniformly mixed was obtained.

[0063] The raw material usage of the present application is: sodium alginate 200 mg, calcium chloride anhydrous powder 10 mg, and cerium nitrate hexahydrate 13.1 mg. Example 7

[0064] The present embodiment provides a preparation method of SA-CC (15:1:2).

[0065] Sodium alginate powder, calcium chloride anhydrous particles and cerium nitrate hexahydrate particles were weighed according to a certain mass ratio and placed in a ball mill jar. The ball milling parameters were controlled as 180 rpm, 8 medium balls and 8 small balls, and 20 minutes. Thus, the SA-CC hemostatic powder uniformly mixed was obtained.

[0066] The raw material usage of the present application is: sodium alginate 150 mg, calcium chloride anhydrous powder 10 mg, and cerium nitrate hexahydrate 26.2 mg. Example 8

[0067] The present embodiment provides a preparation method of SA-CC (10:1:2).

[0068] Sodium alginate powder, calcium chloride anhydrous particles and cerium nitrate hexahydrate particles were weighed according to a certain mass ratio and placed in a ball mill jar. The ball milling parameters were controlled as 180 rpm, 8 medium balls and 8 small balls, and 20 minutes. Thus, the SA-CC hemostatic powder uniformly mixed was obtained.

[0069] The raw material usage of the present application is: sodium alginate 100 mg, calcium chloride anhydrous powder 10 mg, and cerium nitrate hexahydrate 26.2 mg. Example 9

[0070] The embodiment provides a preparation method of SA-CCG (10:1:1:0.1).

[0071] The SA-CC powder and the graphene oxide are weighed according to a certain mass ratio and placed in a ball mill tank. Ball milling parameters are controlled as 180 rpm, 8 medium balls and 8 small balls, and 20 minutes. Thus, the SA-CCG hemostatic powder with uniform mixing is obtained.

[0072] The raw material usage of the application is: 100 mg of sodium alginate, 10 mg of anhydrous calcium chloride powder, 13.1 mg of cerium nitrate hexahydrate and 1 mg of graphene oxide. Example 10

[0073] The embodiment provides a preparation method of SA-CCG (10:1:1:0.3).

[0074] The SA-CC powder and the graphene oxide are weighed according to a certain mass ratio and placed in a ball mill tank. Ball milling parameters are controlled as 180 rpm, 8 medium balls and 8 small balls, and 20 minutes. Thus, the SA-CCG hemostatic powder with uniform mixing is obtained.

[0075] The raw material usage of the application is: 100 mg of sodium alginate, 10 mg of anhydrous calcium chloride powder, 13.1 mg of cerium nitrate hexahydrate and 3 mg of graphene oxide. Example 11

[0076] The embodiment provides a preparation method of SA-CCG (10:1:1:0.5).

[0077] The SA-CC powder and the graphene oxide are weighed according to a certain mass ratio and placed in a ball mill tank. Ball milling parameters are controlled as 180 rpm, 8 medium balls and 8 small balls, and 20 minutes. Thus, the SA-CCG hemostatic powder with uniform mixing is obtained.

[0078] The raw material usage of the application is: 100 mg of sodium alginate, 10 mg of anhydrous calcium chloride powder, 13.1 mg of cerium nitrate hexahydrate and 5 mg of graphene oxide. Example 12

[0079] The embodiment provides a water absorption determination comparison of SA-CC and SA-CCG.

[0080] 0.1 g (m0) of the SA-CC hemostatic powder prepared in the examples 3-8 is weighed, 10 mL of deionized water is added, 10 min of swelling is performed, 4000 rpm centrifugation is performed for 5 min, the supernatant is discarded, and the mass (m1) is weighed. All tests are performed in triplicate.

[0081] Water absorption rate W (%) = (m1-m0) / m0x100%, wherein m0 is the mass before water absorption, and m1 is the mass after water absorption.

[0082] Figure 1 is a water absorption comparison result of the present embodiment, wherein powder 1 is a raw material powder sample prepared by the method of Example 3, powder 2 is a raw material powder sample prepared by the method of Example 4, powder 3 is a raw material powder sample prepared by the method of Example 5, powder 4 is a raw material powder sample prepared by the method of Example 6, powder 5 is a raw material powder sample prepared by the method of Example 7, and powder 6 is a raw material powder sample prepared by the method of Example 8.

[0083] The results show that the water absorption rate of SA-CC (10:1:1) prepared by Example 4, i.e., sodium alginate, calcium chloride, and cerium nitrate in a mass ratio of 10:1:1, is the largest.

[0084] Figure 2 is a water absorption comparison result of SA-CC (10:1:1) and SA-CCG (10:1:1:0.3), and the results show that the water absorption of SA-CCG is slightly improved compared with that of SA-CC. Example 13

[0085] The present embodiment provides a mechanical property determination comparison of SA-CCG.

[0086] A 5 mL centrifuge tube is cut off the cover and the bottom and placed in a 24-well plate. 25 mg of SA-CCG hemostatic powder prepared by Examples 9-11 is weighed and placed in the centrifuge tube, respectively, 1 mL of water is added to form a cylindrical-shaped gel, which is taken out and placed on a universal testing machine to test the compression performance. The diameter of the gel is 12 mm, the bottom area is 1809.6 mm 2 , and the height is accurately measured by using a vernier caliper. The gel parameters are input on the universal testing machine, and the compression test is started. After the test is completed, the stress-strain curve and compression modulus of the gel are obtained. Each group of samples is determined in triplicate.

[0087] Figures 3 and 4 are mechanical property comparison results of the present embodiment, wherein powder 1 is a raw material powder sample prepared by the method of Example 2 (SA-C), powder 2 is a raw material powder sample prepared by the method of Example 3 (SA-CC), powder 3 is a raw material powder sample SA-CCG (10:1:1:0.1) prepared by the method of Example 9, powder 4 is a raw material powder sample SA-CCG (10:1:1:0.3) prepared by the method of Example 10, and powder 5 is a raw material powder sample SA-CCG (10:1:1:0.5) prepared by the method of Example 11.

[0088] The results show that the SA-CCG (10:1:1:0.3) prepared in Example 10, i.e., the mechanical properties of the gel formed by sodium alginate, calcium chloride, cerium nitrate and graphene oxide in a mass ratio of 10:1:1:0.3 are the best.

[0089] Example 14

[0090] This example provides a morphology characterization of the SA-CC and SA-CCG.

[0091] 20 mg of the hemostatic powder prepared in Example 4 and Example 10, respectively, were weighed and placed in 5 mL centrifuge tubes, and 1 mL of water was added to form a gel. The formed gel samples were placed in a -80°C refrigerator for pre-freezing for 12 hours. Then, the lid of the centrifuge tube was cut off, and a sealing film was wrapped thereon and several small holes were punched on the sealing film. After the refrigeration of the freeze-drying machine, vacuum was drawn, and the samples were placed for freeze-drying. The freeze-dried samples were taken out and cut open for taking scanning electron microscope section pictures.

[0092] Figure 5 is the scanning electron microscope results of this example. A (2000 times magnification) and B (500 times magnification) are the gel formed by the hemostatic powder formula of sodium alginate, calcium chloride and cerium nitrate in a mass ratio of 10:1:1, and the porous network structure thereof indicates that the hemostatic powder has the ability of quickly absorbing liquid and converting into a gel. C (2000 times magnification) and D (500 times magnification) are the formula with graphene oxide incorporated, wherein the mass ratio of sodium alginate, calcium chloride, cerium nitrate and graphene oxide is 10:1:1:0.3. The cross-linking degree of the gel with graphene oxide incorporated is increased, and the mechanical properties of the gel are improved. Example 15

[0093] This example provides a comparison of the in-vitro blood clotting performance of the SA-CC and SA-CCG.

[0094] The blood sample for the experiment was configured. The taken blood was placed in an anticoagulant tube and stored in a -24°C refrigerator. Then, 1200 μL of the anticoagulated blood was mixed with 800 μL of a 0.1 mol / L calcium chloride solution (calcium ion was supplemented to simulate the actual environment of the whole blood), to obtain a whole blood sample. 50 μL of the obtained whole blood sample was placed in a 96-well plate. Then, 10 mg of the hemostatic powder of different formulas was placed in the above 96-well plate, and the timing was started. The timing was stopped at 0.5, 1, 1.5, 2, 2.5, 3, 3.5 and 4 minutes, respectively, and PBS was added to the well plate to wash away the uncoagulated blood components. When the blood in the well plate was completely changed into a clot and the PBS could not be washed away, it was the blood clotting time. The hemostatic powder of sodium alginate and calcium chloride in a mass ratio of 10:1 was used as a positive control. The whole blood sample was used as a negative control.

[0095] Figure 6 is a comparison result of blood coagulation in vitro of the present embodiment. The result shows that the blood alone as a control group cannot coagulate by itself within 4 minutes. The sodium alginate powder (SA) alone cannot crosslink with calcium ions in the blood sample to form a gel, which cannot effectively coagulate the blood. The reason is that the solubility of sodium alginate in water is poor (the sodium alginate powder is slowly dissolved in water, and needs to be stirred for several hours to completely dissolve to form a viscous liquid), and a small amount of dissolved sodium alginate forms a gel with calcium ions in the blood, which forms a barrier between the undissolved sodium alginate and the liquid component, hindering the further dissolution and crosslinking of the sodium alginate powder. However, the mixed powder of sodium alginate and calcium chloride (SA-C) can quickly absorb the liquid component in the blood to form a gel, coagulate the blood, and the coagulation time is less than 1 minute (shown by the white dotted line circle). The double crosslinking agent mixed hemostatic powder (SA-CC) prepared from sodium alginate, calcium chloride and cerium nitrate also has good coagulation effect, and can crosslink the blood to form a gel within 1 minute (shown by the white dotted line circle), thereby achieving the effect of coagulation. The hemostatic powder (SA-CCG) prepared by mixing sodium alginate, calcium chloride, cerium nitrate and graphene oxide has the best hemostatic effect, and can crosslink the blood to form a gel within half a minute (shown by the white dotted line circle), proving the excellent in vitro coagulation performance of SA-CCG.

[0096] Example 16

[0097] The present embodiment provides a cytotoxicity test of SA-CCG.

[0098] The SA-CCG prepared in Example 10 was soaked in the cell culture medium for 24 h, and then co-incubated with vascular endothelial cells L929 for 24 h. The CCK8 method was used to determine the cell survival rate.

[0099] Figure 7 is a cytotoxicity determination result of the present embodiment. The result shows that the high concentration of SA-CCG hemostatic powder does not produce obvious toxicity to normal cells, indicating that it has good cell compatibility, and explaining the safety of SA-CCG.

[0100] Example 17

[0101] The present embodiment provides a liver injury model in rats in vivo of SA-CCG.

[0102] After the rats were anesthetized and fixed in a supine position, the left liver lobe was exposed, and a 5 mm long and 3 mm deep incision was made on the liver lobe with a surgical knife. The SA-CCG prepared in Example 10 was sprinkled on the incision site, and the bleeding state was observed. The time difference from the start of the wound bleeding to the stop of the blood seeping from the wound was recorded as the hemostatic time; at the same time, the mass difference of the filter and the hemostatic powder before and after the experiment was recorded as the blood loss.

[0103] Figure 8 is a hemostatic effect of a liver injury model of the present embodiment. Figure 8A is a schematic diagram of the liver injury model bleeding. The results show that the untreated control group has a long bleeding time and a large amount of bleeding, the hemostatic time reaches 266s (Figure 8B), and the amount of bleeding is 283mg (Figure 8C); when the SA-CCG is applied to the wound, the powder immediately becomes gelatinous, producing a tight barrier to inhibit wound bleeding (Figure 8D), the coagulation time is only 97s (Figure 8B), and the amount of bleeding is reduced to 179mg (Figure 8C), proving that the SA-CCG has excellent hemostatic ability. Embodiment 18

[0104] The present embodiment provides a SA-CCG rat tail amputation model in vivo.

[0105] After the rats were anesthetized, they were fixed on their backs, 50% of the length of the tail was cut off, and SA-CCG prepared in Embodiment 10 was sprinkled on the incision site, and the bleeding state was observed. The difference between the time when the wound started to bleed and the time when the blood stopped seeping from the wound was recorded as the hemostatic time; at the same time, the mass difference between the filter before and after the experiment and the hemostatic powder was recorded as the amount of blood loss.

[0106] Figure 9 is a hemostatic effect of a tail amputation model of the present embodiment. Figure 9A is a schematic diagram of the tail amputation model bleeding. The results show that the control group has a long bleeding time and a large amount of bleeding, and the material group (SA-CCG) shows obvious differences. The hemostatic time of the control group is about 732s (Figure 9B), and the amount of bleeding is as high as 1486mg (Figure 9C); in contrast, the SA-CCG group, when the powder is deposited at the bleeding site, the powder quickly absorbs blood and forms a gel thrombus, and as time goes on, the gel tightly adheres to the surface of the wound, and no blood flows out, indicating that the bleeding is effectively controlled (Figure 9D), and the coagulation time is 311s (Figure 9B), and the amount of blood loss is significantly reduced to 352mg (Figure 9C), further proving that it has excellent hemostatic ability.

[0107] In summary, the present application starts from the development of a low-cost, convenient-to-use rapid hemostatic material, uses a large amount of liquid in the bleeding environment as a switch to activate the transformation of the hemostatic powder to hemostatic hydrogel, and then uses coordination chemical crosslinking to improve the viscosity and mechanical strength of the hydrogel, and finally realizes the purpose of rapid hemostasis through component regulation and proportion optimization. The present application can be applied to pre-hospital rapid hemostasis, and provides a new idea for the development of rapid hemostatic materials for field or accidental disaster trauma first aid.

[0108] Although the content of the present application has been described in detail through the above preferred embodiments, it should be recognized that the above description should not be considered as limiting the present application. After reading the above content, various modifications and alternatives of the present application will be apparent to those skilled in the art. Therefore, the scope of protection of the present application should be defined by the appended claims.

Claims

1. A hemostatic powder for rapid hemostasis of traumatic hemorrhage, characterized by, The hemostatic powder comprises sodium alginate, CaCl2 and Ce(NO3)3·6H2O.

2. The hemostatic powder for rapid hemostasis of traumatic hemorrhage according to claim 1, wherein The mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O is (5-20):1:(1-2).

3. The hemostatic powder for rapid hemostasis of traumatic hemorrhage according to claim 2, wherein The mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O is 10:1:

1.

4. The hemostatic powder for rapid hemostasis of traumatic hemorrhage according to claim 1, wherein The hemostatic powder further comprises graphene oxide.

5. The hemostatic powder for use in rapid hemostasis of traumatic hemorrhage according to claim 4, wherein The mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O: graphene oxide is (5-20):1:(1-2):(0.1-0.5).

6. The hemostatic powder for rapid hemostasis of traumatic hemorrhage according to claim 5, wherein The mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O: graphene oxide is 10:1:1:(0.1-0.5).

7. The hemostatic powder for use in rapid hemostasis of traumatic hemorrhage according to claim 6, wherein, The mass ratio of sodium alginate: CaCl2: Ce(NO3)3·6H2O: graphene oxide is 10:1:1:0.

3.

8. A process for the preparation of the haemostatic powder for rapid haemostasis of traumatic bleeding according to any one of claims 1-7, characterized in that, The hemostatic powder comprises the following steps: S1. Grinding calcium chloride anhydrous particles into calcium chloride anhydrous powder, the powder particle size range is 1μm-50μm; S2. Ball-milling the calcium chloride anhydrous powder with sodium alginate and Ce(NO3)3·6H2O to uniformly mix, the powder particle size range is 1μm-50μm.

9. The process for preparation of haemostatic powder for rapid haemostasis of traumatic hemorrhage as claimed in claim 8, wherein, In the step S2, graphene oxide is further added.

10. Use of the haemostatic powder for rapid haemostasis of traumatic bleeding according to any one of claims 1 to 7, characterized in that, The hemostatic powder is used for emergency pre-hospital hemostasis of traumatic massive hemorrhage.

Images