Medical hemostatic gauze with anti-adhesion effect and inorganic array structure

Abstract

The invention discloses medical hemostatic gauze with an anti-adhesion effect and an inorganic array structure. The preparation method of the hemostatic gauze comprises the following steps: dissolving the soluble divalent metal salt, the soluble trivalent aluminum salt and the urea in the deionized water, adding the nanoparticles, and transferring into a hydrothermal kettle; immersing gauze into the solution for hydrothermal reaction, and cleaning and drying to obtain the medical hemostatic gauze with the inorganic array structure. And adding the gauze into a methanol solution of sulfuric acid, a methanol solution of sodium bicarbonate or a methanol solution of hydrochloric acid, and introducing nitrogen for reaction to obtain the intercalated medical hemostatic gauze with the inorganic array structure. By optimizing material combination and microstructure, the obtained gauze with the inorganic array structure can rapidly coagulate after being in contact with blood, meanwhile, by means of unique surface characteristics, excessive adhesion of the gauze and tissue around a wound is effectively blocked, the healing process is accelerated, the problem of intraoperative and postoperative bleeding control is solved, and the healing effect is improved. The tissue adhesion resistance of the gauze is obviously improved, and the injury to a patient during dressing change is reduced.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of medical hemostatic materials, and particularly relates to an inorganic array structure medical hemostatic gauze with an anti-adhesion effect. Background Art

[0002] The development process of medical hemostatic materials is an important witness to the progress of medicine. From the initial simple compression, dressing and the use of natural materials such as cotton and gauze, to the continuous emergence of modern new hemostatic materials, each innovation aims to better solve the hemostasis problem. Traditional gauze, although having the advantages of low cost, wide source and convenient use, faces the challenge of adhesion problems in clinical applications. When the gauze adheres to the wound, protein and cell components in the blood are likely to deposit and coagulate on the surface of the gauze fibers, resulting in the tight adhesion of the gauze to the wound tissue. This not only increases the pain of the patient during dressing change, but also may damage the newly formed granulation tissue, leading to complications such as bleeding and infection, seriously affecting the wound healing. According to statistics, about 30% - 40% of surgical patients suffer additional pain during the postoperative dressing change due to gauze adhesion problems. Especially in delicate surgeries such as ophthalmology and plastic and cosmetic surgeries, the harm of gauze adhesion is more significant.

[0003] To solve the adhesion problem of medical materials, global research teams are committed to the research and development of anti-adhesion technologies. On the one hand, through material modification, such as plasma treatment technology and coating with anti-adhesion coatings, the surface of traditional medical materials is modified to reduce the surface energy, reduce protein adsorption and inhibit adhesion. However, these methods have problems such as insufficient coating stability and poor durability of the modification effect, and the anti-adhesion performance gradually weakens over time or in a complex physiological environment. On the other hand, the development of new materials with inherent anti-adhesion properties, such as biodegradable polymer materials, although showing certain anti-adhesion potential, is relatively weak in the hemostatic function and is difficult to meet the dual requirements of hemostasis and anti-adhesion.

[0004] Inorganic materials have received attention in the medical field due to their unique physical and chemical properties. For example, the application of bioactive glass in the field of bone repair, and silver nanoparticles are often used in the preparation of antibacterial dressings due to their excellent antibacterial properties. In terms of hemostasis, inorganic materials such as zeolite and montmorillonite also show excellent coagulation effects, but they are also troubled by problems such as tissue compatibility and anti-adhesion. Untreated inorganic particles may cause inflammatory reactions and are prone to aggregation and caking after hemostasis, which is not conducive to maintaining the wound healing environment.

[0005] With the development of modern medicine, especially the minimally invasive and refined development of surgical operations, higher requirements are put forward for medical materials. Patients not only expect the success of the operation, but also hope for a smooth and less painful postoperative recovery process. Therefore, it is particularly urgent to develop a medical material that can not only stop bleeding efficiently but also has an excellent anti-adhesion effect. Summary of the Invention

[0006] The object of the present invention is to provide an inorganic array structure medical hemostatic gauze with an anti-adhesion effect. The hemostatic gauze is prepared by mixing gauze with a salt solution containing metal ions and urea, then adding nanoparticles and performing a hydrothermal reaction, and finally washing with water, washing with alcohol, performing an intercalation reaction, and drying to obtain a gauze with a vertically oriented inorganic array structure. By optimizing the material combination and microstructure, the obtained inorganic array structure gauze can quickly coagulate blood after contacting blood. At the same time, with its unique surface properties, it can effectively block the excessive adhesion between the gauze and the surrounding tissues of the wound, reduce the postoperative pain of patients, accelerate the healing process, solve the problem of intraoperative and postoperative bleeding control, significantly improve the anti-tissue adhesion performance of the gauze, reduce the harm to patients during dressing change, and promote wound healing.

[0007] The preparation method of the inorganic array structure medical hemostatic gauze with an anti-adhesion effect is as follows: Dissolve soluble divalent metal salts, soluble trivalent aluminum salts and urea in deionized water, add nanoparticles and disperse evenly, then transfer to a hydrothermal autoclave; then immerse the gauze in it and perform a hydrothermal reaction at 120 - 160 °C for 12 - 24 h; after the reaction is completed, cool to room temperature, take out the gauze, wash with deionized water and ethanol, and dry at 60 - 80 °C for 12 - 24 h to obtain the inorganic array structure medical hemostatic gauze.

[0008] The molar ratio of the soluble divalent metal salt to the soluble trivalent aluminum salt is 1 - 5:1, and the molar ratio of the soluble divalent metal salt to urea is 1:5 - 10.

[0009] The soluble divalent metal salt is selected from one or more of magnesium salts, calcium salts, divalent iron salts, and divalent manganese salts.

[0010] The nanoparticles are one or more of calcium-based nanoparticles, iron-based nanoparticles, titanium dioxide nanoparticles, chitosan nanoparticles, and zinc ion nanoparticles.

[0011] The addition amount of the nanoparticles is 0.5 - 3% of the sum of the masses of the soluble divalent metal salt and the soluble trivalent aluminum salt.

[0012] The gauze is at least one of pure cotton gauze, fully cotton bleached gauze, degreased gauze, elastic bandage gauze, wound dressing gauze, non-woven fabric gauze, and composite non-woven fabric gauze.

[0013] Perform an intercalation reaction on the obtained inorganic array structure medical hemostatic gauze: Add the obtained inorganic array structure medical hemostatic gauze to a methanol solution of sulfuric acid with a concentration of 0.02 - 0.1 mol / L, a methanol solution of sodium bicarbonate, or a methanol solution of hydrochloric acid, and react under nitrogen for 12 - 24 h; after the reaction is completed, dry the gauze to obtain the intercalated inorganic array structure medical hemostatic gauze.

[0014] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. The inorganic array structure medical hemostatic gauze with anti-adhesion effect of the present invention has good hydrophobic and anti-adhesion effects, and at the same time has good anti-fouling effect.

[0015] 2. The inorganic array structure medical hemostatic gauze with anti-adhesion effect of the present invention has good acute wound hemostasis performance and good hemostasis effect in animal experiments.

[0016] 3. The preparation process of the inorganic array structure medical hemostatic gauze with anti-adhesion effect of the present invention is simple, has the possibility of large-scale production, is expected to fill the key gaps in the current medical material field, and bring a revolutionary breakthrough to the medical cause. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 XRD diagram of ordinary degreased gauze.

[0018] Figure 2 XRD diagram of the inorganic array structure medical hemostatic gauze in Example 1.

[0019] Figure 3 Scanning electron microscope image of ordinary degreased gauze.

[0020] Figure 4 Scanning electron microscope image of the inorganic array structure medical hemostatic gauze in Example 1.

[0021] Figure 5 Diagram of the contact angle of ordinary degreased gauze.

[0022] Figure 6 Diagram of the contact angle of the inorganic array structure medical hemostatic gauze in Example 1.

[0023] Figure 7 Diagram of the anti-fouling experiment of ordinary degreased gauze.

[0024] Figure 8 Diagram of the anti-fouling experiment of the inorganic array structure medical hemostatic gauze in Example 1.

[0025] Figure 9 Diagram of the bleeding area before and after the filter paper in the liver injury model. DETAILED DESCRIPTION OF THE INVENTION

[0026] The following is a detailed description of the embodiments of the present invention. The embodiments are implemented on the premise of the technical solution of the present invention, and the detailed implementation manners and specific operation processes are given. However, the protection scope of the present invention is not limited to the following embodiments. Example 1

[0027] Dissolve 4.066 g of MgCl₂·6H₂O, 2.414 g of AlCl₃·6H₂O, and 8.409 g of CO(NH₂)₂ in 100 ml of deionized water. Then, uniformly disperse 0.162 g (particle size 10 nm) of CaO₂ nanoparticles into the above mixed solution, and transfer it to a hydrothermal autoclave. Then, immerse 2.5 g of degreased gauze into it, carry out hydrothermal reaction at 120 °C for 12 h. After the reaction is completed, cool it to room temperature, take out the gauze, ultrasonically clean it with deionized water and ethanol, and finally dry the gauze in an oven at 60 °C.

[0028] Figure 1 and Figure 2 are the XRD patterns of ordinary degreased gauze and the gauze loaded with inorganic array structure obtained in Example 1 respectively. It can be seen from the figure that characteristic diffraction peaks of crystal planes such as (003), (006), (012), (015), and (018) appear at 11.6°, 23.1°, 34.9°, 39.5°, and 47.1° on the gauze loaded with inorganic array structure, indicating the successful growth of the inorganic array structure.

[0029] Figure 3 is the SEM image of the ordinary gauze in Example 1. It can be seen that the surface of the gauze fiber is smooth and there is no load of inorganic array structure, while in Example 1, obvious hexagonal nanosheets grow vertically on the surface of the gauze with inorganic array structure ( Figure 4 ) Example 2

[0030] (1) Dissolve 4.066 g of MgCl₂·6H₂O, 2.414 g of AlCl₃·6H₂O, and 8.409 g of CO(NH₂)₂ in 100 ml of deionized water. Then, uniformly disperse 0.113 g (particle size 20 nm) of iron oxide nanoparticles into the above mixed solution, and transfer it to a hydrothermal autoclave. Then, immerse 2.5 g of degreased gauze into it, carry out hydrothermal reaction at 120 °C for 15 h. After the reaction is completed, cool it to room temperature, take out the gauze, ultrasonically clean it with deionized water and ethanol, and finally dry the gauze in an oven at 60 °C.

[0031] (2) Place the gauze obtained in step (1) into a three-necked flask, add 150 mL of a methanol solution of sulfuric acid with a concentration of 0.0241 mol / L to it, and react under nitrogen for 12 h; after the reaction is completed, dry the gauze in an oven at 60 °C. Example 3

[0032] (1) Dissolve 4.066 g of MgCl₂·6H₂O, 2.414 g of AlCl₃·6H₂O, and 8.409 g of CO(NH₂)₂ in 100 ml of deionized water. Then, uniformly disperse 0.194 g of titanium dioxide nanoparticles (with a particle size of 40 nm) into the above mixed solution, and transfer it to a hydrothermal reactor. Then, immerse 2.5 g of degreased gauze into it, and carry out a hydrothermal reaction at 140 °C for 18 h. After the reaction is completed, cool it to room temperature, take out the gauze, ultrasonically clean it with deionized water and ethanol, and finally dry the gauze in an oven at 60 °C.

[0033] (2) Place the gauze obtained in step (1) in a three-necked flask, add 150 mL of a methanol solution of sodium bicarbonate with a concentration of 0.1 mol / L to it, and react under a nitrogen atmosphere for 12 h. After the reaction is completed, dry the gauze in an oven at 60 °C. Example 4

[0034] (1) Dissolve 4.066 g of MgCl₂·6H₂O, 2.414 g of AlCl₃·6H₂O, and 8.409 g of CO(NH₂)₂ in 100 ml of deionized water. Then, uniformly disperse 0.194 g of chitosan nanoparticles into the above mixed solution, and transfer it to a hydrothermal reactor. Then, immerse 2.5 g of degreased gauze into it, and carry out a hydrothermal reaction at 160 °C for 24 h. After the reaction is completed, cool it to room temperature, take out the gauze, ultrasonically clean it with deionized water and ethanol, and finally dry the gauze in an oven at 60 °C.

[0035] (2) Place the gauze obtained in step (1) in a three-necked flask, add 150 mL of a methanol solution of hydrochloric acid with a concentration of 0.0435 mol / L to it, and react under a nitrogen atmosphere for 12 h. After the reaction is completed, dry the gauze in an oven at 60 °C.

[0036] Take out the gauze, ultrasonically clean it with deionized water 1 - 2 times first, then ultrasonically clean it with ethanol once, and finally dry the gauze in an oven at 60 °C.

[0037] Evaluate the hemostatic effect of the inorganic array structure hemostatic gauze prepared in the above examples. The experiment uses mice as the research object to conduct an in vitro 1 - minute liver injury experiment. Examples 1 - 4 are labeled T1 - T4 respectively (the ctrl group is ordinary degreased gauze). The bleeding areas before and after the filter paper are statistically analyzed.

[0038] In terms of hemostasis for a large amount of bleeding (liver defect model), the T3 group has better hemostatic ability. Through mouse experiments, it can be proved that the inorganic array structure gauzes with different interlayer anions obtained in Examples 1 - 4 all have better hemostatic effects compared with ordinary degreased gauze.

[0039] Figure 5 and Figure 6It is shown that growing an inorganic array structure on the gauze can achieve a hydrophobic effect, effectively preventing blood wetting and penetration. This means that when the hydrophobic gauze is applied to a wound, it can quickly form a barrier to resist the flow and diffusion of blood, and has a good anti-adhesion effect, being easy to peel off from the wound.

[0040] Figure 7 and Figure 8 Respectively, when ordinary gauze and the gauze loaded with the inorganic array structure in Example 1 are placed in the dye, it can be observed that the ordinary gauze is completely immersed in the dye due to its hydrophilicity, while the gauze loaded with the inorganic array structure in Example 1 floats on the dye without being contaminated by the dye due to its certain hydrophobicity, indicating a reduced chance of adhesion between the gauze and the wound tissue.

[0041] Figure 9 It is a graph of the filter paper of the liver injury model and the statistical bleeding (filter paper) area before and after the liver injury model filter paper. It is observed that the gauze loaded with the inorganic array structure has a certain degree of hemostatic effect.

Claims

1. A method for preparing an inorganic array structure medical hemostatic gauze with anti-adhesion effect, characterized in that: The specific operation of the preparation method is: dissolving soluble divalent metal salt, soluble trivalent aluminum salt and urea in deionized water, adding nanoparticles and dispersing them evenly, and then transferring them into a hydrothermal kettle; then immersing gauze in the kettle, The reaction was carried out at 120-160° C. for 12-24 hours. After the reaction was completed, the gauze was cooled to room temperature, and the gauze was taken out, washed with deionized water and ethanol, and dried at 60-80° C. for 12-24 hours to obtain the inorganic array structure medical hemostatic gauze.

2. The preparation method according to claim 1, characterized in that: The molar ratio of the soluble divalent metal salt to the soluble trivalent aluminum salt is 1-5:1, and the molar ratio of the soluble divalent metal salt to urea is 1:5-10.

3. The preparation method according to claim 1, characterized in that: The soluble divalent metal salt is selected from one or more of magnesium salt, calcium salt, divalent iron salt and divalent manganese salt.

4. The preparation method according to claim 1, characterized in that: The nanoparticles are one or more of calcium-based nanoparticles, iron-based nanoparticles, titanium dioxide nanoparticles, chitosan nanoparticles, and zinc ion nanoparticles.

5. The preparation method according to claim 1, characterized in that: The added amount of the nanoparticles is 0.5-3% of the total mass of the soluble divalent metal salt and the soluble trivalent aluminum salt.

6. The preparation method according to claim 1, characterized in that: The gauze is at least one of pure cotton gauze, pure cotton bleached gauze, degreased gauze, elastic bandage gauze, gauze for wound surface, non-woven gauze and composite non-woven gauze.

7. The preparation method according to any one of claims 1 to 6, characterized in that: The prepared inorganic array structure medical hemostatic gauze is subjected to an intercalation reaction: the inorganic array structure medical hemostatic gauze is added to a methanol solution of sulfuric acid, a methanol solution of sodium bicarbonate or a methanol solution of hydrochloric acid with a concentration of 0.02-0.1 mol / L, and nitrogen is passed through the solution to react for 12-24 hours; after the reaction is completed, the gauze is dried to obtain the intercalated inorganic array structure medical hemostatic gauze.

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