阅读说明：本技术 一种止血复合材料及其制备方法 (Hemostatic composite material and preparation method thereof ) 是由 张理火 周平 于 2021-09-29 设计创作，主要内容包括：本发明公开一种止血复合材料及其制备方法：包括(1)将介孔硅和纳米氧化锌分散于含凝血因子XIII和纤维蛋白原的溶液中,搅拌,抽滤,干燥,制得组分A；(2)将介孔硅和纳米氧化锌分散于含凝血酶和氯化钙的溶液中,搅拌,抽滤,干燥,制得组分B；(3)将组分A与组分B混合,得到止血复合材料。本发明以介孔硅和纳米氧化锌作为原料,介孔硅通过快速吸收水分,加速负载组分的快速溶解,启动反应,促发纤维蛋白胶形成,实现快速止血；介孔硅作为载体,可以显著提高止血复合材料的流动性,更易精准给药,进一步提高止血效果。纳米氧化锌具备的抗菌和加速创面愈合功能,可以进一步提高治疗效果。本发明方法制得的止血复合材料具有显著的临床优势。(The invention discloses a hemostatic composite material and a preparation method thereof: dispersing mesoporous silicon and nano zinc oxide in a solution containing blood coagulation factor XIII and fibrinogen, stirring, filtering, and drying to obtain a component A; (2) dispersing mesoporous silicon and nano zinc oxide in a solution containing thrombin and calcium chloride, stirring, carrying out suction filtration, and drying to obtain a component B; (3) and mixing the component A and the component B to obtain the hemostatic composite material. According to the invention, mesoporous silicon and nano zinc oxide are used as raw materials, and the mesoporous silicon can accelerate the rapid dissolution of a load component by rapidly absorbing water, start a reaction, promote the formation of fibrin glue and realize rapid hemostasis; the mesoporous silicon is used as a carrier, so that the fluidity of the hemostatic composite material can be obviously improved, the precise administration is easier, and the hemostatic effect is further improved. The nano zinc oxide has the functions of resisting bacteria and accelerating wound healing, and can further improve the treatment effect. The hemostatic composite material prepared by the method has obvious clinical advantages.)

1. A method for preparing a hemostatic composite material, comprising the steps of:

(1) preparation of component A: dispersing mesoporous silicon and nano zinc oxide in a solution containing blood coagulation factor XIII and fibrinogen, stirring, carrying out suction filtration, and drying to obtain a component A;

(2) preparation of component B: dispersing mesoporous silicon and nano zinc oxide in a solution containing thrombin and calcium chloride, stirring, carrying out suction filtration, and drying to obtain a component B;

(3) preparing a hemostatic composite material: and mixing the component A and the component B to obtain the hemostatic composite material.

2. The method for preparing a hemostatic composite material according to claim 1, wherein the stirring in step (1) and step (2) is room temperature stirring, and the stirring time is 20-40 minutes; the drying is vacuum drying, the drying temperature is 35-40 ℃, and the drying time is 180 minutes.

3. The method for preparing a hemostatic composite material according to claim 1, wherein the mesoporous silicon in step (1) and step (2) has a pore size of 20-30 nm; the particle size of the nano zinc oxide is 10-60 nm.

4. The preparation method of the hemostatic composite material according to claim 1, wherein the mesoporous silicon and the nano zinc oxide are ultrasonically dispersed in the solution containing the blood coagulation factor XIII and the fibrinogen in the step (1), and the content of the mesoporous silicon is 10-30mg/ml and the content of the nano zinc oxide is 0.2-0.6 mg/ml.

5. The method for preparing a hemostatic composite material according to claim 1, wherein the content of blood coagulation factor XIII in the solution containing blood coagulation factor XIII and fibrinogen is 10-20IU/ml, and the content of fibrinogen is 25-35 mg/ml.

6. The preparation method of a hemostatic composite material according to claim 1, wherein the mesoporous silicon and the nano zinc oxide are ultrasonically dispersed in the solution containing thrombin and calcium chloride in the step (2), and the content of the mesoporous silicon is 10-30mg/ml and the content of the nano zinc oxide is 0.2-0.6 mg/ml.

7. The method for preparing a hemostatic composite material according to claim 1, wherein the thrombin content in the solution containing thrombin and calcium chloride in step (2) is 2-8mg/ml, and the calcium chloride content is 5-15 mg/ml.

8. The method for preparing a hemostatic composite material according to claim 1, wherein the step (3) of preparing a hemostatic composite material comprises: mixing the component A and the component B in a three-dimensional mixer to obtain a hemostatic composite material; the mass ratio of the component A to the component B is 1: 1.

9. the method for preparing a hemostatic composite material according to claim 8, wherein the mixing speed of the three-dimensional mixer is 50-100rpm, and the mixing time is 45-90 minutes.

10. A hemostatic composite material, prepared by the method of any one of claims 1-9.

Technical Field

The invention relates to the technical field of biomedical materials, in particular to a hemostatic composite material and a preparation method thereof.

Background

The problems of difficult suturing of clinical wound bleeding, postoperative suturing and bleeding and the like often bring troubles to the completion of operations and postoperative recovery of patients, and the problems can be effectively solved by selecting a proper medical adhesive. The fibrin adhesive is a local hemostatic, is used for assisting in treating the bleeding of burn wounds, abdominal incisions of general surgery, liver operation wounds and vascular surgery wounds, and has the effects of tissue sealing, wound healing promotion and the like. The fibrin adhesive consists of fibrinogen freeze-dried powder and a diluent thereof, thrombin freeze-dried powder and a diluent thereof, the whole preparation process is long and tedious, the clinical use and operation are complex, and the preparation time is long; and the product needs low-temperature storage and cold-chain transportation, which causes higher cost and limits the wide application of the product.

Therefore, the fibrinogen and thrombin composite powder (CN201010200864.X, CN201480012686.4 and CN202110322473.3) is inoculated, four components are changed into single component, the product is simpler, the preparation period is short, the product can be stored at room temperature, and the fibrinogen and thrombin composite powder can be used in clinical application. However, in the actual preparation process, the prepared composite powder is poor in fluidity and easy to aggregate, the hemostatic effect is influenced, and in addition, the prepared composite powder has no antibacterial effect.

In recent years, the importance of metal or metal oxide nanoparticles in medicine and industry has been more and more emphasized. Among them, the zinc oxide nanoparticles have photocatalytic ability and can generate active oxygen, and compared with other metal nanomaterials, the zinc oxide nanomaterials have better biocompatibility and biodegradability, and are proved to have the effects of antibiosis and wound healing acceleration, and the like, and have passed the advantages of FDA certification and the like, thereby attracting the attention of many researchers.

Disclosure of Invention

The invention provides a hemostatic composite material and a preparation method thereof, aiming at the problems of complex preparation process, high cost, complex clinical use and operation and the like of the existing fibrin adhesive in the background technology and the problems of poor fluidity, easy aggregation, no antibacterial effect and the like of fibrin composite powder.

The invention is realized by the following technical scheme:

a method for preparing a hemostatic composite material, comprising the steps of:

(1) preparation of component A: dispersing mesoporous silicon and nano zinc oxide in a solution containing blood coagulation factor XIII and fibrinogen, stirring, carrying out suction filtration, and drying to obtain a component A;

(2) preparation of component B: dispersing mesoporous silicon and nano zinc oxide in a solution containing thrombin and calcium chloride, stirring, carrying out suction filtration, and drying to obtain a component B;

(3) preparing a hemostatic composite material: and mixing the component A and the component B to obtain the hemostatic composite material.

Specifically, in the preparation process of the hemostatic composite material, the mesoporous silicon can quickly absorb moisture, accelerate the quick dissolution of the load component, start the reaction and promote the formation of fibrin glue, thereby realizing quick hemostasis. Preferably, the nano zinc oxide selected by the invention has excellent antibacterial property, can accelerate the healing function of the wound surface, and can further improve the treatment effect. The hemostatic composite material prepared by the method has obvious clinical advantages and wider clinical application and market prospect.

Further, the preparation method of the hemostatic composite material comprises the following steps: stirring in the step (1) and the step (2) is room-temperature stirring, and the stirring time is 20-40 minutes; the drying is vacuum drying, the drying temperature is 35-40 ℃, and the drying time is 180 minutes.

Further, the preparation method of the hemostatic composite material comprises the following steps: the aperture of the mesoporous silicon in the step (1) and the step (2) is 20-30 nm; the particle size of the nano zinc oxide is 10-60 nm.

Further, the preparation method of the hemostatic composite material comprises the following steps: ultrasonically dispersing the mesoporous silicon and the nano zinc oxide into a solution containing blood coagulation factor XIII and fibrinogen, wherein the content of the mesoporous silicon is 10-30mg/ml, and the content of the nano zinc oxide is 0.2-0.6 mg/ml.

Further, the preparation method of the hemostatic composite material comprises the following steps: in the step (1), in a solution containing blood coagulation factor XIII and fibrinogen, the content of the blood coagulation factor XIII is 10-20IU/ml, and the content of the fibrinogen is 25-35 mg/ml.

Further, the preparation method of the hemostatic composite material comprises the following steps: and (2) ultrasonically dispersing the mesoporous silicon and the nano zinc oxide into a solution containing thrombin and calcium chloride, wherein the content of the mesoporous silicon is 10-30mg/ml, and the content of the nano zinc oxide is 0.2-0.6 mg/ml.

Further, the preparation method of the hemostatic composite material comprises the following steps: in the solution containing thrombin and calcium chloride, the content of thrombin is 2-8mg/ml, and the content of calcium chloride is 5-15 mg/ml.

Further, the preparation method of the hemostatic composite material comprises the following steps: step (3), preparation of the hemostatic composite material: mixing the component A and the component B in a three-dimensional mixer to obtain a hemostatic composite material; the mass ratio of the component A to the component B is 1: 1.

further, the preparation method of the hemostatic composite material comprises the following steps: the mixing speed of the three-dimensional mixer is 50-100rpm, and the mixing time is 45-90 minutes.

The hemostatic composite material is characterized by being prepared by the preparation method. The hemostatic composite material prepared by the method has the advantages of high hemostatic speed, antibacterial function, simple preparation process, short period, obvious clinical advantage and wide market prospect.

The invention has the beneficial effects that:

(1) the preparation method of the hemostatic composite material solves the problems of complex process, high preparation cost and the like in the existing production process of the fibrin adhesive, the hemostatic composite material prepared by the method solves the problem of inconvenient clinical use of the fibrin adhesive, and the scheme of the invention also solves the problems of poor fluidity, easy aggregation, no antibacterial action and the like of fibrin composite powder.

(2) The preparation method of the hemostatic composite material provided by the invention takes the mesoporous silicon and the nano zinc oxide as raw materials, and the mesoporous silicon can accelerate the rapid dissolution of the load component by rapidly absorbing water, start the reaction and promote the formation of fibrin glue, thereby realizing rapid hemostasis. The mesoporous silicon is used as a carrier, so that the fluidity of the hemostatic composite material can be obviously improved, the precise administration is easier, and the hemostatic effect can be further improved. Wound infection can delay wound recovery and endanger life safety, and the nano zinc oxide has the functions of resisting bacteria and accelerating wound healing, so that the treatment effect can be further improved. The hemostatic composite material prepared by the method has obvious clinical advantages and wider clinical application and market prospect.

(3) The hemostatic composite material prepared by the method has the advantages of high hemostatic speed, antibacterial property and the like, and the preparation method of the hemostatic composite material is simple and short in period.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.

FIG. 1 is a graph of the hemostatic effect of the hemostatic composite material prepared in examples 1-3 and a commercially available fibrin adhesive;

FIG. 2 is a graph showing the bacteriostatic effects of the hemostatic composite material prepared in examples 1-3 on Staphylococcus aureus.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

A preparation method of a hemostatic composite material comprises the following steps:

(1) preparation of component A: ultrasonically dispersing mesoporous silicon with the pore diameter of 25nm and nano zinc oxide with the particle diameter of 30nm in a solution containing blood coagulation factor XIII and fibrinogen to ensure that the content of the mesoporous silicon is 10mg/ml and the content of the nano zinc oxide is 0.2 mg/ml; then stirring for 30 minutes at room temperature, then carrying out suction filtration, and then carrying out vacuum drying for 150 minutes at 37 ℃ to obtain a component A; in a solution containing blood coagulation factor XIII and fibrinogen, the content of the blood coagulation factor XIII is 10IU/ml, and the content of the fibrinogen is 25 mg/ml;

(2) preparation of component B: ultrasonically dispersing mesoporous silicon with the pore diameter of 25nm and nano zinc oxide with the particle diameter of 30nm in a solution containing thrombin and calcium chloride, wherein the content of the mesoporous silicon is 10mg/ml, and the content of the nano zinc oxide is 0.2 mg/ml; then stirring for 30 minutes at room temperature, then carrying out suction filtration, and then carrying out vacuum drying for 150 minutes at 37 ℃ to obtain a component B; in a solution containing thrombin and calcium chloride, the content of the thrombin is 2mg/ml, and the content of the calcium chloride is 5 mg/ml;

(3) preparing a hemostatic composite material: mixing the component A and the component B according to a mass ratio of 1: 1, mixing and placing in a three-dimensional mixer for mixing (the mixing speed of the three-dimensional mixer is 50rpm, and the mixing time is 45 minutes), thus obtaining the hemostatic composite material.

Example 2

A preparation method of a hemostatic composite material comprises the following steps:

(1) preparation of component A: ultrasonically dispersing mesoporous silicon with the pore diameter of 30nm and nano zinc oxide with the particle diameter of 20nm in a solution containing blood coagulation factor XIII and fibrinogen to ensure that the content of the mesoporous silicon is 20mg/ml and the content of the nano zinc oxide is 0.4 mg/ml; then stirring for 35 minutes at room temperature, then carrying out suction filtration, and then carrying out vacuum drying for 130 minutes at 40 ℃ to obtain a component A; in a solution containing blood coagulation factor XIII and fibrinogen, the content of the blood coagulation factor XIII is 15IU/ml, and the content of the fibrinogen is 30 mg/ml;

(2) preparation of component B: ultrasonically dispersing mesoporous silicon with the pore diameter of 20nm and nano zinc oxide with the particle diameter of 60nm in a solution containing thrombin and calcium chloride, wherein the content of the mesoporous silicon is 20mg/ml, and the content of the nano zinc oxide is 0.4 mg/ml; then stirring for 25 minutes at room temperature, then carrying out suction filtration, and then carrying out vacuum drying for 160 minutes at 35 ℃ to obtain a component B; in a solution containing thrombin and calcium chloride, the content of the thrombin is 5mg/ml, and the content of the calcium chloride is 10 mg/ml;

(3) preparing a hemostatic composite material: mixing the component A and the component B according to a mass ratio of 1: 1, mixing and placing in a three-dimensional mixer for mixing (the mixing speed of the three-dimensional mixer is 75rpm, and the mixing time is 90 minutes), thus obtaining the hemostatic composite material.

Example 3

A preparation method of a hemostatic composite material comprises the following steps:

(1) preparation of component A: ultrasonically dispersing mesoporous silicon with the pore diameter of 20nm and nano zinc oxide with the particle diameter of 50nm in a solution containing blood coagulation factor XIII and fibrinogen to ensure that the content of the mesoporous silicon is 30mg/ml and the content of the nano zinc oxide is 0.6 mg/ml; then stirring for 40 minutes at room temperature, then carrying out suction filtration, and then carrying out vacuum drying for 150 minutes at 35 ℃ to obtain a component A; in a solution containing blood coagulation factor XIII and fibrinogen, the content of the blood coagulation factor XIII is 20IU/ml, and the content of the fibrinogen is 35 mg/ml;

(2) preparation of component B: ultrasonically dispersing mesoporous silicon with the aperture of 30nm and nano zinc oxide with the particle size of 40nm in a solution containing thrombin and calcium chloride, wherein the content of the mesoporous silicon is 30mg/ml, and the content of the nano zinc oxide is 0.6 mg/ml; then stirring for 35 minutes at room temperature, then carrying out suction filtration, and then carrying out vacuum drying for 140 minutes at 37 ℃ to obtain a component B; in a solution containing thrombin and calcium chloride, the content of the thrombin is 8mg/ml, and the content of the calcium chloride is 15 mg/ml;

(3) preparing a hemostatic composite material: mixing the component A and the component B according to a mass ratio of 1: 1, mixing and placing in a three-dimensional mixer for mixing (the mixing speed of the three-dimensional mixer is 100rpm, and the mixing time is 70 minutes), thus obtaining the hemostatic composite material.

Test example 1

Testing the hemostatic effect: the hemostatic composite materials prepared in the above examples 1 to 3 were tested for hemostatic effect by the following procedure: constructing a rat liver bleeding model, anesthetizing the rat, shaving the abdomen, and taking a middle incision of the abdomen; the abdomen is opened layer by layer, the liver is exposed, a small part of the left outer lobe is cut off quickly at a position 0.8cm above the lower edge of the left outer lobe of the liver of the rat to cause bleeding, the length of the cut is about 20mm, the width of the cut is about 5mm, the hemostatic composite materials prepared in the above examples 1-3 are rapidly administered after the cut, a blank control group (a blank test without any hemostatic material) and a commercially available fibrin adhesive are set for comparison, the bleeding time of the liver wound surface is recorded, and the hemostatic effect of the hemostatic materials prepared in the examples on the liver bleeding wound surface is examined, and the result is shown in fig. 1; as can be seen from fig. 1, the hemostatic composite materials prepared in examples 1-3 of the present invention have significant hemostatic effects compared to the blank control group; the hemostatic composites prepared in examples 1-3 of the present invention all bleed less time than commercially available fibrin adhesives.

Test example 2

And (3) testing the antibacterial effect: the hemostatic composites prepared in examples 1-3 above were tested for antimicrobial efficacy: staphylococcus aureus is used as a test object, the hemostatic composite materials prepared in the embodiments 1-3 are respectively subjected to bacteriostatic performance tests according to the requirements of GB 15979 appendix C of 2002, the test results are shown in figure 2, and as can be seen from figure 2, the hemostatic materials prepared in the embodiments 1-3 of the present invention have an obvious inhibiting effect on Staphylococcus aureus.

The above-mentioned preferred embodiments of the present invention are provided for illustration only and not for the purpose of limiting the invention. Obvious variations or modifications of the present invention are within the scope of the present invention.