CN111973798A

CN111973798A - Absorbable hemostatic microspheres capable of rapidly stopping bleeding and preparation method thereof

Info

Publication number: CN111973798A
Application number: CN202010827209.0A
Authority: CN
Inventors: 车七石; 刘少辉
Original assignee: Guangzhou Rainhome Pharm and Tech Co Ltd
Current assignee: Guangzhou Rainhome Pharm and Tech Co Ltd
Priority date: 2020-08-17
Filing date: 2020-08-17
Publication date: 2020-11-24
Anticipated expiration: 2040-08-17
Also published as: CN111973798B

Abstract

The invention relates to the field of medical materials, and provides a rapid hemostatic absorbable microsphere and a preparation method thereof aiming at the problem of slow hemostasis speed, wherein the technical scheme is as follows: the silver nanoparticle comprises chitosan, dimethyl siloxane, starch, sodium carboxymethylcellulose and nano-silver, wherein the mass ratio of the chitosan to the dimethyl siloxane to the starch to the sodium carboxymethylcellulose to the nano-silver is (2-5) to (0.5-0.9): (2 to 5), (1 to 3), (0.01 to 0.05); the hemostatic absorbable microsphere is safe, reliable, rapid in hemostasis, remarkable in bacteriostatic effect, good in biocompatibility, capable of being degraded and absorbed quickly after hemostasis, free of any harmful substance and convenient to use.

Description

Absorbable hemostatic microspheres capable of rapidly stopping bleeding and preparation method thereof

Technical Field

The invention relates to the field of medical materials, in particular to a quick hemostatic absorbable microsphere and a preparation method thereof.

Background

One of the main causes of death in the process of accidents and surgical treatment is excessive blood loss, and when emergencies occur or surgical operations are performed, the bleeding time is shortened, the bleeding amount is reduced, the infection caused by the contact of wounds and the outside is prevented, and the subsequent treatment and the wound healing of patients are facilitated. The traditional hemostasis method is mainly to attach a hemostasis material (such as a bandage, a tourniquet, a sponge, cotton yarn and the like) to a wound surface, and press the wound surface by using mechanical external force or prevent the wound surface from continuously bleeding by using the water absorption of the material, but the material has poor effect when facing a complex wound surface part and shape or when bleeding occurs in a large area. The powder hemostatic product is not affected by the size and the position of the wound surface, is convenient and quick to use and has unique advantages. Therefore, the development of a novel powdery hemostatic product is a new hot point of hemostatic products. In addition, the currently commonly used topical hemostatic materials mainly include porous sponge materials (collagen sponge), powder materials (zeolite, potato starch), fiber materials, hemostatic gauze materials, and the like.

Chinese patent CN 105126152B discloses a carboxymethyl cellulose sodium chitosan composite hemostatic powder, which is prepared by mixing a fish skin carboxymethyl cellulose sodium solution and a chitosan solution, stirring at a low temperature, then freeze-drying, carrying out superfine grinding, and then carrying out disinfection and sterilization. According to the invention, chitosan is added into the prepared fish skin sodium carboxymethyl cellulose, so that the synergistic effect among materials can be exerted, the water absorption and the adhesion of the composite material are improved, the hemostatic performance of the composite material is improved, and the chitosan antibacterial and bacteriostatic performance is achieved. The mechanical property, the hemostatic property and the wound healing capability of the composite material are improved, and the composite material becomes a hemostatic with excellent comprehensive performance. Although the composite material has good hemostatic and antibacterial properties, the hemostatic speed still cannot achieve the effect of rapidly stopping blood, and an effective protective layer cannot be formed.

At present, the existing hemostatic materials are various in types, have certain hemostatic effect, but still have slow hemostatic speed, and the protective effect of a protective layer formed by the hemostatic materials is not good enough no matter whether the hemostatic materials are degraded or not.

Disclosure of Invention

Aiming at the defects in the prior art, the first purpose of the invention is to provide a rapid hemostatic absorbable microsphere which has the advantage of rapid material hemostasis.

In order to achieve the purpose, the invention provides the following technical scheme:

the quick hemostasis absorbable microsphere comprises chitosan, dimethyl siloxane, starch, sodium carboxymethyl cellulose and nano silver, wherein the mass ratio of the chitosan to the dimethyl siloxane to the starch to the sodium carboxymethyl cellulose to the nano silver is (2-5) to (0.5-0.9): (2 to 5), (1 to 3), (0.01 to 0.05).

Furthermore, the mass ratio of the chitosan, the dimethyl siloxane, the starch, the sodium carboxymethyl cellulose and the nano silver is (3-4): (0.6-0.8): (2-4): 1-2): 0.02-0.04.

Furthermore, the mass ratio of the chitosan to the dimethyl siloxane to the starch to the sodium carboxymethyl cellulose to the nano silver is 4:0.7:2:1: 0.02.

Furthermore, the rapid hemostasis absorbable microsphere has a porous structure, and the pore diameter is 0.2-0.75 μm.

Further, the size of the rapid hemostasis absorbable microsphere is 50-100 mu m, and the specific surface area is 1.31-1.56 m²/g。

Further, the size of the rapid hemostasis absorbable microspheres is 65 mu m, and the specific surface area is 1.45m²/g。

The inventor finds that the starch is used as a hemostatic absorbable microsphere carrier, the chitosan, the sodium carboxymethylcellulose and the nano silver are mixed to form a micro-shell wrapping the microsphere carrier, the surface of the micro-shell is uneven to form a hemostatic absorbable microsphere with a porous structure, the chitosan and the dimethyl siloxane are mixed to form a layer of charged protective film on the surface of the micro-shell, so that the external bacterial infection is prevented, the micro-shell is safe and reliable, platelets, thrombin and the like in blood are gathered on the surface of the protective film under the surface charging effect of the protective film, the micro-shell promotes the generation of the platelets and accelerates the generation of fibrinogen, so that the rapid absorption of water in the blood is realized, the concentration of the blood is promoted, and the rapid hemostasis absorbable microsphere is realized, the hemostatic absorbable microsphere prepared by the method is safe and reliable, the hemostasis is rapid, the bacteriostatic effect is obvious, and the biocompatibility of the hemostatic absorbable microsphere, can be quickly degraded and absorbed after hemostasis, does not generate any harmful substance, and is convenient to use.

The wound dressing contains sodium carboxymethyl cellulose and dimethyl siloxane, wherein the dimethyl siloxane can effectively lock moisture after the sodium carboxymethyl cellulose rapidly absorbs the moisture at the wound, so that the external compression on the wound is increased, the blood coagulation is further accelerated, and the effect of protecting the wound is achieved.

According to the invention, the sodium carboxymethyl cellulose and the nano-silver are mixed to form the microsphere-wrapped micro-shell, the three components are combined to have obvious antibacterial effect, and the protective film formed on the surface of the micro-shell can effectively prevent external bacterial infection.

Aiming at the defects in the prior art, the second purpose of the invention is to provide a preparation method of the rapid hemostatic absorbable microspheres, which has the advantage of simple preparation.

A preparation method of absorbable microspheres with rapid hemostasis function comprises the following steps:

s1, mixing the following components in a mass ratio of (2-5) to (0.5-0.9): (2-5) (1-3) (0.01-0.05) weighing chitosan, dimethyl siloxane, starch, sodium carboxymethyl cellulose and nano silver, adding deionized water for dissolving, stirring until complete dissolution is achieved to obtain a solution with the concentration of 1.8-2.6mg/mL, and preparing a water phase;

s2, adding 96 parts of white oil, 2 parts of span 80 and 2 parts of Tween 80 into a stirring kettle to form a mixed solution serving as an emulsifier, mixing and preheating to 55-60 ℃ to prepare an oil phase;

s3, preheating the water phase obtained in the step S1 to 60-65 ℃, and then slowly dropwise adding the water phase into the oil phase obtained in the step S2, wherein the volume ratio of the water phase to the oil phase is 1: (2-6), uniformly spraying and mixing the mixture under high pressure, and emulsifying the mixture for 10-20 min at the rotating speed of 100-200 r/min and the water bath temperature of 45-55 ℃ to obtain uniform emulsion;

s4, after the emulsification is finished, cooling for 5-10 min, dropwise adding 1-2 mL of glutaraldehyde solution with the concentration of 20-80%, and performing crosslinking and solidification for 25-30 min to obtain a crosslinked polymer, wherein the rotation speed is kept unchanged in the process, and continuously stirring;

s5, after cross-linking, pouring 25-30 mL of acetone with the temperature of 4 ℃ into the cross-linked polymer obtained in the step S4, dehydrating and flocculating for 20-40 min, keeping the rotating speed unchanged in the process, continuously stirring, centrifuging to obtain hemostatic microspheres, respectively cleaning for 3-5 times by using petroleum ether, and freeze-drying to obtain the microspheres

S6, crushing the microspheres obtained in the step S5, sieving, and performing aseptic treatment to obtain the microsphere.

Further, the freeze-drying in the step S5 is to freeze-dry for 7-9h at-35 ℃ to-45 ℃ and under the vacuum degree of 8-10 Pa.

Further, the screening size of step S6 is 150-300 meshes.

In addition, the application of the rapid hemostatic absorbable microspheres in preparing hemostatic materials is also provided.

In conclusion, the invention has the following beneficial effects:

1. the rapid hemostatic absorbable microsphere provided by the invention is safe, reliable, rapid in hemostasis, remarkable in bacteriostatic effect, good in biocompatibility, capable of being degraded and absorbed rapidly after hemostasis, free of any harmful substance and convenient to use.

2. The starch as a hemostatic absorbable microsphere carrier is mixed with the sodium carboxymethylcellulose and the nano-silver to form a micro-shell wrapping the microsphere carrier, and the chitosan and the dimethyl siloxane are mixed to form a layer of charged protective film on the surface of the micro-shell, so that the moisture in blood is quickly absorbed, the concentration of the blood is promoted, and the quick hemostasis is realized.

3. According to the invention, chitosan, sodium carboxymethylcellulose and nano-silver are mixed to form the microsphere-coated micro-shell, the combination of the chitosan, the sodium carboxymethylcellulose and the nano-silver has an obvious antibacterial effect, and the protective film formed on the surface of the micro-shell can effectively prevent external bacterial infection.

Detailed Description

The present invention will be described in further detail with reference to examples.

In the following examples, chitosan sold by Saibei Hirsch science and technology, Inc. was used as the chitosan with CAS number 9012-76-4.

In the following examples, the starch used was a starch sold by Shanghai-derived leaf Biotech Co., Ltd, CAS number 9005-25-8.

In the following examples, nano silver sold by Nannochemical technology, Guangzhou under CAS number 7440-22-4 is used.

In the following examples, dimethylsiloxane sold by Aladdin under CAS number 63148-62-9 was used.

In the following examples, sodium carboxymethylcellulose sold by Shijia Shunyi chemical Co., Ltd is used as the sodium carboxymethylcellulose, and the CAS number is 9004-32-4.

Example 1

s1, weighing chitosan, starch, nano-silver, dimethyl siloxane and sodium carboxymethyl cellulose according to a mass ratio of 2:0.5:2:1:0.01, adding deionized water to dissolve, stirring until the solution is completely dissolved to obtain a solution with a concentration of 1.8mg/mL, and preparing a water phase;

s2, adding 96 parts of white oil, 2 parts of span 80 and 2 parts of Tween 80 into a stirring kettle to form a mixed solution serving as an emulsifier, mixing and preheating to 55 ℃ to prepare an oil phase;

s3, preheating the water phase obtained in the step S1 to 60 ℃, and slowly dripping the water phase into the oil phase obtained in the step S2, wherein the volume ratio of the water phase to the oil phase is 1: 2, spraying and mixing uniformly under high pressure, and emulsifying for 10min under the conditions of the rotating speed of 100r/min and the water bath temperature of 45 ℃ to obtain uniform emulsion;

s4, after the emulsification is finished, cooling for 5min, dropwise adding 1mL of 20% glutaraldehyde solution, carrying out crosslinking and solidification for 25min to obtain a crosslinked polymer, and continuously stirring while keeping the rotating speed unchanged in the process;

s5, after crosslinking, pouring 25mL of acetone with the temperature of 4 ℃ into the crosslinked polymer obtained in the step S4, dehydrating and flocculating for 20min, keeping the rotating speed unchanged in the process, continuously stirring and centrifuging to obtain microspheres, respectively washing the microspheres for 3 times by using petroleum ether, and freeze-drying the microspheres for 7h at the temperature of-35 to-45 ℃ under the vacuum condition to obtain the microspheres;

s6, crushing the microspheres obtained in the step S5, sieving the crushed microspheres with a 150-mesh sieve, and performing ultraviolet sterile treatment to obtain the absorbable microspheres with rapid hemostasis.

The obtained rapidly hemostatic absorbable microsphere has size of about 100 μm and specific surface area of 1.31m²The pore diameter of the microspheres is 0.2 mu m.

Example 2

s1, weighing chitosan, starch, nano-silver, dimethyl siloxane and sodium carboxymethyl cellulose according to a mass ratio of 3:0.6:2:1:0.02, adding deionized water to dissolve, stirring until the solution is completely dissolved to obtain a solution with a concentration of 2.2mg/mL, and preparing a water phase;

s2, adding 96 parts of white oil, 2 parts of span 80 and 2 parts of Tween 80 into a stirring kettle to form a mixed solution serving as an emulsifier, mixing and preheating to 60 ℃ to prepare an oil phase;

s3, preheating the water phase obtained in the step S1 to 65 ℃, slowly dropwise adding the water phase into the oil phase obtained in the step S2, wherein the volume ratio of the water phase to the oil phase is 1:4, uniformly spraying and mixing the water phase and the oil phase at high pressure, and emulsifying the mixture for 15min at the conditions of the rotating speed of 150r/min and the water bath temperature of 50 ℃ to obtain uniform emulsion;

s4, cooling for 10min after emulsification is finished, dropwise adding 2mL of 50% glutaraldehyde solution, and crosslinking and curing for 30min to obtain a crosslinked polymer, wherein the rotation speed is kept unchanged in the process, and stirring is continuously carried out;

s5, after crosslinking, pouring 30mL of acetone with the temperature of 4 ℃ into the crosslinked polymer obtained in the step S4, dehydrating and flocculating for 30min, keeping the rotating speed unchanged in the process, continuously stirring, centrifuging to obtain microspheres, respectively washing the microspheres for 4 times by using petroleum ether, and freeze-drying for 8h at the temperature of-35 to-45 ℃ under the vacuum condition to obtain the microspheres;

s6, crushing the microspheres obtained in the step S5, sieving the crushed microspheres with a 200-mesh sieve, and performing ultraviolet sterile treatment to obtain the absorbable rapid hemostasis microspheres.

The obtained rapid hemostatic absorbable microspheres have a size of about 74 μm and a specific surface area of 1.48m²The microspheres have a pore size of 0.5 μm/g.

Example 3

s1, weighing chitosan, starch, nano-silver, dimethyl siloxane and sodium carboxymethyl cellulose according to a mass ratio of 5:0.9:5:3:0.05, adding deionized water to dissolve, stirring until the solution is completely dissolved to obtain a solution with a concentration of 2.5mg/mL, and preparing a water phase;

s3, preheating the water phase obtained in the step S1 to 65 ℃, slowly dropwise adding the water phase into the oil phase obtained in the step S2, wherein the volume ratio of the water phase to the oil phase is 1:6, uniformly spraying and mixing the water phase and the oil phase at high pressure, and emulsifying the mixture for 20min at the conditions of the rotating speed of 200r/min and the water bath temperature of 55 ℃ to obtain uniform emulsion;

s5, after crosslinking, pouring 30mL of acetone with the temperature of 4 ℃ into the crosslinked polymer obtained in the step S4, dehydrating and flocculating for 40min, keeping the rotating speed unchanged in the process, continuously stirring, centrifuging to obtain microspheres, respectively washing the microspheres for 5 times by using petroleum ether, and freeze-drying for 9h at the temperature of minus 35 ℃ to minus 45 ℃ under the vacuum condition to obtain the microspheres;

s6, crushing the microspheres obtained in the step S5, sieving the crushed microspheres with a 250-mesh sieve, and performing ultraviolet sterile treatment to obtain the absorbable rapid hemostasis microspheres.

The obtained rapid hemostatic absorbable microspheres have a size of about 55 μm and a specific surface area of 1.56m²The microspheres have a pore size of 0.75 μm/g.

Example 4

s1, weighing chitosan, starch, nano-silver, dimethyl siloxane and sodium carboxymethyl cellulose according to a mass ratio of 4:0.8:4:2:0.04, adding deionized water to dissolve, stirring until the solution is completely dissolved to obtain a solution with a concentration of 2.6mg/mL, and preparing a water phase;

s4, cooling for 10min after emulsification is finished, dropwise adding 2mL of 80% glutaraldehyde solution, and crosslinking and curing for 30min to obtain a crosslinked polymer, wherein the rotation speed is kept unchanged in the process, and stirring is continuously carried out;

Example 5

s1, weighing chitosan, starch, nano-silver, dimethyl siloxane and sodium carboxymethyl cellulose according to a mass ratio of 4:0.7:2:1:0.02, adding deionized water to dissolve, stirring until the solution is completely dissolved to obtain a solution with a concentration of 2.6mg/mL, and preparing a water phase;

The obtained rapid hemostatic absorbable microspheres have a size of about 74 μm and a specific surface area of 1.45m²The microspheres have a pore size of 0.5 μm/g.

Comparative example 1

In comparison with example 5, the step of S1 in comparative example 1 does not add dimethylsiloxane component, and the remaining components and steps are the same as in example 5.

Comparative example 2

Compared with example 5, the mass ratio of chitosan, sodium carboxymethyl cellulose and nano silver in the step of S1 in comparative example 2 is 1:1:1, and the rest of the components and steps are the same as those in example 5.

Comparative example 3

In comparison with example 5, in comparative example 3, no sodium carboxymethylcellulose was added in step S1, and the remaining ingredients and steps were the same as in example 5.

Comparative example 4

In comparison with example 5, in comparative example 3, the step of S1 is not added with nano silver, and the remaining components and steps are the same as those of example 5.

Test example 1 biocompatibility test of absorbable hemostatic microspheres

Test materials: the quick hemostasis absorbable microspheres prepared in example 1, example 2, example 3, example 4, example 5, comparative example 1, comparative example 2, comparative example 3 and comparative example 4 were prepared in a blank group, and the blank group was not treated.

1. The test method comprises the following steps:

(1) 0.1mg of each of the rapid hemostatic absorbable microspheres prepared in example 1, example 2, example 3, example 4, example 5, comparative example 1, comparative example 2, comparative example 3 and comparative example 4 was placed in a 24-well cell culture plate.

(2) Preparing DMEM cell culture medium containing 10% fetal calf serum, digesting human skin keratinocyte from cell culture bottle, centrifuging, and diluting with culture medium to 1 × 10⁴Cell suspension per mL.

(3) The cell suspension was then added to a well plate containing rapidly hemostatic absorbable microspheres at 1.5mL per well, and after incubation in a 37 ℃ incubator for 1 and 3 days, 20. mu.l of MTT solution (5mg/mL in PBS) was added per well. And continuing to incubate for 4 hours, terminating the culture, carefully absorbing and removing culture supernatant in the holes, adding 150 mu l of DMSO into each hole, oscillating for 10 minutes, detecting the absorbance of the cells by using an enzyme-labeling instrument, adding the same cell suspension into the blank group, performing the same treatment with the hole plate containing the rapid hemostatic absorbable microspheres, and finally obtaining a cell activity result. And (3) test results: the test results are shown in table 1.

TABLE 1 statistical results of cell Activity

Item	Day one	The third day	The seventh day
				Example 1	0.328±0.006	0.548±0.013	0.875±0.016
Example 2	0.338±0.013	0.536±0.012	0.842±0.023
				Example 3	0.337±0.006	0.534±0.012	0.857±0.026
Example 4	0.326±0.012	0.534±0.016	0.804±0.010
				Example 5	0.345±0.015	0.535±0.013	0.876±0.006
Comparative example 1	0.327±0.006	0.518±0.013	0.854±0.012
				Comparative example 2	0.338±0.07	0.516±0.08	0.865±0.004
Comparative example 3	0.334±0.004	0.507±0.008	0.824±0.003
				Comparative example 4	0.324±0.005	0.538±0.004	0.834±0.005
Blank group	0.338±0.015	0.543±0.009	0.855±0.008

As can be seen from the experimental results in Table 1, the activity of human skin keratinocytes in each example group is similar to that of the blank group on the first day, the third day and the seventh day, which indicates that the cells can grow normally in the presence of the rapid hemostatic absorbable microspheres, so that the rapid hemostatic absorbable microspheres prepared by the present invention have good biocompatibility.

Test example 2 blood coagulation Performance test of rapidly hemostatic absorbable microspheres

1. Test materials: examples 1, 2, 3, 4, 5, 1, 2, 3 and 4, and comparative example 4.

2. The test method comprises the following steps:

(1) randomly dividing 40 rats with the mass of 250-300g into a blank control group and 4 rats in each group, namely, the blank control group, the example 1, the example 2, the example 3, the example 4, the example 5, the comparative example 1, the comparative example 2, the comparative example 3 and the comparative example 4;

(2) pentobarbital is injected into abdomen for anesthesia, and the back is unhaired and sterilized, and then the size of the product is 1cm²The skin of (1) has model success that the blood of the wound surface is quickly exosmosed and the bleeding is active;

(3) immediately spraying 0.40g of corresponding rapid hemostatic absorbable microspheres on the wound surfaces of the groups of example 1, example 2, example 3, example 4, example 5, comparative example 1, comparative example 2, comparative example 3 and comparative example 4, covering sterile gauze and starting timing; the blank group is directly covered with sterile gauze, and then the bleeding of the wound surface is observed every 10s until the bleeding stops, and the bleeding is stopped by removing the gauze. The time of hemostasis was recorded and the adhesion of the hemostatic material to the wound surface was observed.

3. And (3) test results: the test results are shown in table 2.

Item	Hemostasis time(s)
		Example 1	40±20
Example 2	40±10
		Example 3	40±20
Example 4	40±30
		Example 5	30±20
Comparative example 1	80±30
		Comparative example 2	90±20
Comparative example 3	100±30
		Comparative example 4	80±20
Blank group	300±40

From the table 2, it can be seen that, compared with the blank group, each group of the rapid hemostasis absorbable microspheres has a certain hemostasis effect, but compared with each example group, each control group can see that the example group has a better hemostasis effect, and the hemostasis time is very short, which indicates that each example group can rapidly stanch, the addition of dimethyl siloxane can increase the hemostasis effect, and the carboxymethyl cellulose sodium and chitosan can improve the blood coagulation effect, and the comprehensive test result shows that the interaction system of each component in the invention enables the rapid hemostasis absorbable microspheres to increase the hemostasis effect, and the hemostasis time of the example 5 is the shortest, 30 ± 20s, and the example 5 is the best example.

Test example 3 testing of bacteriostatic Properties of rapidly hemostatic absorbable microspheres

1. Test materials: the quick hemostasis absorbable microspheres prepared by the method of example 1, example 2, example 3, example 4 and example 5.

2. The test method comprises the following steps: dissolving the 5 groups of rapid hemostatic absorbable microspheres in 0.2mg and 0.3mL of water on a culture dish, respectively, and inoculating with 0.3mL of physiological saline solution at a concentration of 7.0 × 10⁴0.1mL of Pseudomonas aeruginosa in CFU/mL, and the number of Pseudomonas aeruginosa was measured after 30 min.

3. And (3) test results: the results are shown in Table 3.

TABLE 3 results of the bacteriostatic properties of the rapidly hemostatic absorbable microspheres

Item	Pseudomonas aeruginosa (CFU/mL)
		Example 1	5.46×10³
Example 2	5.52×10³
		Example 3	5.61×10³
Example 4	5.68×10³
		Example 5	4.57×10³
Comparative example 1	5.97×10³
		Comparative example 2	5.83×10³
Comparative example 3	7.96×10³
		Comparative example 4	9.12×10³
Physiological saline group	12.23×10⁴

As can be seen from table 3, compared with the normal saline group, the number of pseudomonas aeruginosa in each example group is significantly reduced, which indicates that the rapid hemostasis absorbable microspheres prepared by the invention have a good bacteriostatic effect, and meanwhile, as can be seen from the comparative example results, the bacteriostatic effects of comparative examples 1 and 2 are insufficient in the effects of examples 1 to 5, and sodium carboxymethyl cellulose and nano silver are not added in comparative example 3 and comparative example 4, respectively, so that the obtained bacteriostatic effect is inferior to that of examples 1 to 5, which indicates that the addition of sodium carboxymethyl cellulose and nano silver can significantly improve the bacteriostatic effect of the rapid hemostasis absorbable microspheres, and the bacteriostatic effect of example 5 is the best.

By combining the experimental results, the rapid hemostatic absorbable microspheres prepared by the invention have good hemostatic and bacteriostatic properties and good biocompatibility, and example 5 is the best example of the invention.

The embodiments of the present invention are preferred embodiments of the present invention, and the scope of the present invention is not limited by these embodiments, so: all equivalent changes made according to the structure, shape and principle of the invention are covered by the protection scope of the invention.

Claims

1. A rapid hemostasis absorbable microsphere is characterized in that: the silver nanoparticle comprises chitosan, dimethyl siloxane, starch, sodium carboxymethylcellulose and nano-silver, wherein the mass ratio of the chitosan to the dimethyl siloxane to the starch to the sodium carboxymethylcellulose to the nano-silver is (2-5) to (0.5-0.9): (2 to 5), (1 to 3), (0.01 to 0.05).

2. The rapid hemostatic absorbable microsphere of claim 1, wherein: the mass ratio of the chitosan, the dimethyl siloxane, the starch, the sodium carboxymethylcellulose and the nano silver is (3-4): (0.6-0.8): 2-4): 1-2): 0.02-0.04.

3. The rapid hemostatic absorbable microsphere of claim 1, wherein: the mass ratio of the chitosan to the dimethyl siloxane to the starch to the sodium carboxymethyl cellulose to the nano silver is 4:0.7:2:1: 0.02.

4. The rapidly hemostatic absorbable microsphere of any one of claims 1 to 3, wherein: the rapid hemostasis absorbable microsphere has a porous structure, and the aperture is 0.2-0.75 mu m.

5. The rapidly hemostatic absorbable microsphere of any one of claims 1 to 3, wherein: the rapid hemostasis canThe size of the absorption microspheres is 50-100 mu m, and the specific surface area is 1.31-1.56 m²/g。

6. The rapidly hemostatic absorbable microsphere of any one of claims 1 to 3, wherein: the size of the rapid hemostasis absorbable microsphere is 65 mu m, and the specific surface area is 1.45m²/g。

7. The method for preparing an absorbable hemostatic microsphere, according to claim 1, wherein the method comprises the following steps: the method comprises the following steps:

s1, mixing the following components in a mass ratio of (2-5) to (0.5-0.9): (2-5) (1-3) (0.01-0.05) weighing chitosan, dimethyl siloxane, starch, sodium carboxymethylcellulose and nano silver, adding deionized water for dissolving, stirring until the solution is completely dissolved to obtain a solution with the concentration of 1.8-2.6mg/mL, and preparing into a water phase;

s4, after the emulsification is finished, cooling for 5-10 min, dropwise adding 1-2 mL of glutaraldehyde solution with the concentration of 20-80%, and performing crosslinking and solidification for 25-30 min to obtain a crosslinked polymer, wherein the rotation speed is kept unchanged in the process, and stirring is continuously performed;

s5, after crosslinking, pouring 25-30 mL of acetone with the temperature of 4 ℃ into the crosslinked polymer obtained in the step S4, dehydrating and flocculating for 20-40 min, keeping the rotating speed unchanged in the process, continuously stirring, centrifuging to obtain microspheres, respectively washing the microspheres for 3-5 times by using petroleum ether, and freeze-drying to obtain the microspheres;

8. The method for preparing an absorbable hemostatic microsphere, according to claim 7, wherein the method comprises the following steps: the step S5 is to freeze-dry the mixture for 7 to 9 hours at the temperature of between 35 ℃ below zero and 45 ℃ below zero in vacuum.

9. The method for preparing an absorbable hemostatic microsphere, according to claim 7, wherein the method comprises the following steps: the screening size of step S6 is 150-300 mesh.

10. Use of a rapid hemostatic absorbable microsphere according to any one of claims 1 to 6 in the preparation of a hemostatic material.