CN110464868B - Silicate clay modified hemostatic material and preparation method thereof - Google Patents

Abstract

The invention provides a silicate clay modified hemostatic material and a preparation method thereof, wherein the hemostatic material is formed by compounding silicate clay and high polymer through electrostatic spinning; the mass ratio of the silicate clay to the high polymer is 0.5-2.5: 1; the silicate clay comprises kaolinite, halloysite, attapulgite or montmorillonite; wherein, part of silicon hydroxyl of the silicate clay is combined with the hydrogen bond of the high polymer, and the rest silicon hydroxyl plays the roles of hemostasis and hydrophily on the surface of the hemostatic material. The method comprises the following steps: firstly, carrying out pretreatment and ultrasonic crushing on silicate clay, then mixing with a high polymer ethanol solution to obtain an electrostatic spinning solution, and finally carrying out electrostatic spinning to obtain the silicate clay modified hemostatic material. The obtained hemostatic material has the advantages of high hemostatic speed, convenient use, favorable wound healing, good biocompatibility, low cost and the like.

Description

Silicate clay modified hemostatic material and preparation method thereof

Technical Field

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

Background

The research and application of novel hemostatic materials is an important topic in the global field of medicine and biomaterial science. The high-efficiency hemostatic material has important significance for saving life no matter clinical surgery or massive hemorrhage of human bodies caused by various sudden accidents. The current clinical hemostatic materials are different types such as oxidized cellulose, gelatin sponge, fibrin glue and the like. The hemostatic effects of the commonly used hemostatic materials are very different, and the application conditions are different, so that the requirements of all emergency situations cannot be completely met.

Silicate clay minerals are widely distributed and diversified in nature, and are valuable natural resources. The silicate clay mineral has fine particles, strong plasticity, good associativity, large specific surface area, electronegativity on the particles, good physical adsorption and surface chemical activity, safety, no toxicity and the like. Silicate clay mineral has been proved to have better blood coagulation function in the medical field, can selectively absorb water in blood and effectively concentrate blood coagulation active substances; the platelet is aggregated and adhered, and simultaneously, the blood coagulation factor can be excited, and the intrinsic blood coagulation path is started, thereby achieving the purpose of blood coagulation.

Chinese patent CN106039383A discloses a compound notoginseng kaolin bamboo fiber hemostatic gauze and a preparation method thereof, the hemostatic gauze comprises a base material of a primary or regenerated bamboo fiber material, a hemostatic material bonded on the base material, and a binder for binding the hemostatic material to the base material, wherein the hemostatic material comprises a kaolin or kaolinite hemostatic clay material and notoginseng hemostatic powder. The hemostatic gauze has the following problems: the amount of the hemostatic material adhering is limited and the particles adhering to the substrate are easily detached, which leads to a decrease in its hemostatic ability and difficulties in subsequent handling.

Therefore, it is necessary to provide a hemostatic material with high hemostatic speed, convenient use and low cost.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides a silicate clay modified hemostatic material and a preparation method thereof, and aims to compound silicate clay and high polymer into a hemostatic material with a stable structure by using an electrostatic spinning technology, so that the hemostatic material has the advantages of high hemostatic speed, convenience in use and low cost.

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

a silicate clay modified hemostatic material is prepared by compounding silicate clay and high polymer through electrostatic spinning; the mass ratio of the silicate clay to the high polymer is 0.5-2.5: 1; the silicate clay comprises kaolinite, halloysite, attapulgite or montmorillonite; wherein, part of silicon hydroxyl of the silicate clay is combined with the hydrogen bond of the high polymer, and the rest silicon hydroxyl plays roles of hemostasis and hydrophily on the surface of the hemostatic material; the high polymer comprises polyvinylpyrrolidone, polyethylene, levorotatory polylactic acid, polyethylacrylate or polyvinyl alcohol.

Preferably, the silicate clay is halloysite, the halloysite is dispersed halloysite nanoparticles, the hemostatic material is a 3D network structure composed of a plurality of fiber bundles, and the fiber bundles are formed by compounding nano halloysite and high polymers through electrostatic interaction.

Preferably, the silicate clay is attapulgite, the attapulgite is dispersed attapulgite nanoparticles, and the hemostatic material is formed by compounding the dispersed attapulgite nanoparticles with a high polymer through electrostatic interaction.

The invention also provides a preparation method of the silicate clay modified hemostatic material, which comprises the following steps:

(1) carrying out pretreatment and ultrasonic crushing on silicate clay;

(2) dissolving the high polymer in ethanol to prepare a high polymer ethanol solution with the concentration of 0.1-0.3 g/mL;

(3) mixing the silicate clay treated in the step (1) with the high polymer ethanol solution obtained in the step (2) to obtain an electrostatic spinning solution;

wherein the mass ratio of the silicate clay to the high polymer is 0.5-2.5: 1;

(4) performing electrostatic spinning on the electrostatic spinning solution obtained in the step (3) to obtain a silicate clay modified hemostatic material;

wherein the silicate clay comprises kaolinite, halloysite, attapulgite or montmorillonite; the high polymer comprises polyvinylpyrrolidone, polyethylene, levorotatory polylactic acid, polyethylacrylate or polyvinyl alcohol;

the parameters of electrostatic spinning are as follows: the rotating speed of the roller is 450-500 r/min; the receiving distance is 17-21 cm; the voltage of the positive electrode is 10-12 kV; the voltage of the negative electrode is 2-3 kV.

Preferably, when the silicate clay is halloysite, attapulgite or montmorillonite, the pretreatment comprises grinding, washing and centrifuging.

Preferably, when the silicate clay is kaolinite, the pretreatment includes grinding, washing, centrifuging and pillaring.

Preferably, the pillared liquid used for pillaring treatment is a dimethyl sulfoxide aqueous solution.

Preferably, the ultrasonic crushing power is 400-800W, and the time is 100-150 min.

Preferably, the silicate clay has an average particle size of less than 1 μm after ultrasonication.

Preferably, the liquid outlet speed of electrostatic spinning is 0.05 mL/min.

When the silicate clay is halloysite: the halloysite nanotube obtained by pretreatment has a large amount of silicon hydroxyl and strong agglomeration, can be combined with high polymer in a nanotube group form through hydrogen bonds, and forms a 3D reticular film woven by numerous fiber bundles through electrostatic spinning.

In the halloysite modified hemostatic material, a halloysite nano tube forms a halloysite group with a certain size, and the action of silicon hydroxyl has certain attraction to a high polymer, so that a fiber bundle formed by the high polymer becomes thin, and the pore structure of the whole film becomes more. In the hemostasis process, on one hand, the thinner fiber bundles provide more space for blood cells to enter so as to be more fully contacted with the halloysite, and on the other hand, the agglomerated halloysite shows stronger halloysite hemostasis characteristics and can activate coagulation factor XII and activate platelets to accelerate hemostasis. Meanwhile, the whole hydrophilicity of the film becomes stronger, which is more beneficial to quickly absorbing water in blood, so that the blood becomes thick, the blood cell concentration is improved, the blood flow is limited, and the purpose of stopping bleeding is finally achieved.

The high polymer has the heat shrinkage of the high polymer material, so that the high polymer can continuously shrink in a normal room temperature environment, and finally, the high polymer only keeps about 10% of the original area. And the large number of pores between the fiber bundles are reduced or eliminated due to shrinkage, so that the hemostatic performance of the film is further restricted. After the halloysite is added, the silicon hydroxyl of the halloysite is combined with the high polymer, so that the integral shrinkage of the high polymer is inhibited, and more than 70% of the area of the original film is reserved. Meanwhile, the phenomenon that polymer molecules in a small range in the film are close to the halloysite clusters is caused, so that fiber bundles formed by the polymer become thin, and the pore structure of the whole film becomes more.

When the silicate clay is attapulgite: the pretreated attapulgite nanorod can be mutually combined with a high polymer through hydrogen bonds due to the dissociation property of the rod crystal bundle and a large amount of silicon hydroxyl groups, and a 3D reticular film woven by fiber bundles is formed through electrostatic spinning; then, the 3D reticular film is developed into a film with a surface with a few attapulgite residual particles due to the heat shrinkage of the high polymer material.

The high polymer has the heat shrinkage of the high polymer material, so that the high polymer can continuously shrink in a normal room temperature environment, and finally, the high polymer only keeps about 10% of the original area. And the large number of pores between the fiber bundles are reduced or eliminated due to shrinkage, so that the hemostatic performance of the film is further restricted. The formed attapulgite has the thickness of the hemostatic film, the partially dissociated attapulgite is fused in the film to support the frame structure, stabilize the whole structure, inhibit the further shrinkage of high polymer, and can keep more than 70% of the area of the original film.

On the surface of a single fiber bundle of the film, residual attapulgite particles serve as functional particles, the hydrophilicity of the surface of the film is improved, and the silicon-oxygen tetrahedron structure has certain hemostatic capacity and can activate platelets to accelerate hemostasis. Can be attached to the wound in the hemostasis process, absorb blood plasma and condense blood cells to accelerate hemostasis.

The scheme of the invention has the following beneficial effects:

(1) according to the invention, silicate clay with a hemostatic function is combined with an electrostatic spinning technology for the first time to prepare the novel film hemostatic material, compared with hemostatic dressing powder or a hemostatic material bonded on a base material, the silicate clay modified hemostatic material is convenient to use when used for stopping bleeding of wounds, and the material can be more tightly attached to wound surfaces due to the water absorption and the bonding property of the material.

(2) Part of silicon hydroxyl of the silicate clay is combined with hydrogen bonds of high polymer in the hemostatic material to form a stable structure; the rest silicon hydroxyl plays the roles of hemostasis and hydrophilicity on the surface of the material, and the obtained hemostatic material has the advantages of stable performance, high hemostasis speed, convenience in use, contribution to wound healing, good biocompatibility and low cost.

(3) The high polymer without silicate clay is unstable in structure and is easy to generate polycondensation, so that the pore structure disappears, the specific surface area is reduced, the structural advantage brought by the electrostatic spinning process is damaged, and the hemostatic effect is poor (comparative example 1); after the silicate clay is modified, the overall shrinkage of the high polymer is inhibited, and the silicate clay provides support for the overall structure of the composite material, so that the shrinkage phenomenon is reduced, the pore structure of the composite material is increased, and the hemostatic effect is improved (examples 1 to 3).

Drawings

FIG. 1 is an SEM image of a halloysite-modified hemostatic material obtained in example 1 of the invention;

FIG. 2 is an SEM image of the attapulgite modified hemostatic material obtained in example 3 of the invention;

fig. 3 is an SEM image of the polyvinylpyrolidone electrospun film of comparative example 1 of the invention.

Detailed Description

In order to make the technical problems, technical solutions and advantages to be solved by the present invention clearer, the following detailed description is given with reference to specific embodiments.

Example 1

(1) Preparation of halloysite nanotubes:

weighing 5.0g of crude halloysite after grinding, washing and centrifuging, adding 500mL of deionized water, and ultrasonically crushing for 2h under 1500W power to obtain halloysite nanorods with the average size below 1 μm.

(2) Preparation of halloysite modified hemostatic material:

dissolving 1.0g of polyvinylpyrrolidone in 10mL of absolute ethyl alcohol, adding 1.50g of halloysite nanorods, and stirring for 36h in water bath at normal temperature; carrying out electrostatic spinning, setting the rotating speed of a roller to be 500r/min, setting the distance (receiving distance) between a needle head and the roller to be 21cm, setting the liquid outlet speed to be 0.05mL/min, setting the positive voltage to be 10kV, setting the negative voltage to be 2kV, and preparing the halloysite modified hemostatic material, wherein the SEM atlas is shown in figure 1: the halloysite groups in the halloysite modified hemostatic material are distributed in a 3D network structure formed by overlapping halloysite and polyvinylpyrrolidone composite fiber bundles, the halloysite groups are formed by mutual attraction of electrostatic interaction generated by silicon hydroxyl of halloysite crystals, the fiber bundles are formed by compounding nano halloysite with polyvinylpyrrolidone through electrostatic interaction, and the halloysite groups are compounded with polyvinylpyrrolidone through electrostatic interaction and then connected with the fiber bundles; the nano halloysite is a dispersed halloysite nanoparticle.

(3) Hemostasis test:

rats were anesthetized with 10% chloral hydrate (0.3ml/100g) by intraperitoneal injection, fixed in the supine position, sterilized, and the skin, muscle and peritoneum were cut layer by layer to expose the liver, taking the median incision of the abdomen about 5cm long. After the right lobe of the liver was fully exposed, a 1X 1cm square was drawn with a sharp knife at the center to a depth of about 0.5 cm. Removing liver tissue in the boundary by using tissue scissors, and scraping the wound surface by using tissue forceps to ensure that the liver wound surface has obvious blood seepage. The hemostatic material prepared in example 1 was placed on the wound surface, fully covered and attached to the liver tissue, and medical gauze was pressed and timed properly over the outer wound surface of the material, and the complete cessation time of bleeding was recorded as 120 seconds.

Example 2

(1) Preparation of halloysite nanotubes:

weighing 5.0g of crude halloysite after grinding, washing and centrifuging, adding 500mL of deionized water, and ultrasonically crushing for 2h under 1500W power to obtain halloysite nanorods with the average size below 1 μm.

(2) Preparation of halloysite modified hemostatic material:

dissolving 1.0g of polyvinylpyrrolidone in 10mL of absolute ethyl alcohol, adding 0.50g of halloysite nanorods, and stirring for 36h in water bath at normal temperature; and (3) carrying out electrostatic spinning, wherein the rotating speed of a roller is set to be 500r/min, the distance between a needle head and the roller is 21cm, the liquid outlet speed is 0.05mL/min, the positive voltage is 10kV, and the negative voltage is 2kV, so that the halloysite modified hemostatic material is prepared.

(3) Hemostasis test:

rats were anesthetized with 10% chloral hydrate (0.3ml/100g) by intraperitoneal injection, fixed in the supine position, sterilized, and the skin, muscle and peritoneum were cut layer by layer to expose the liver, taking the median incision of the abdomen about 5cm long. After the right lobe of the liver was fully exposed, a 1X 1cm square was drawn with a sharp knife at the center to a depth of about 0.5 cm. Removing liver tissue in the boundary by using tissue scissors, and scraping the wound surface by using tissue forceps to ensure that the liver wound surface has obvious blood seepage. The hemostatic material prepared in example 1 was placed on the wound surface, fully covered and attached to the liver tissue, and the outer side of the wound surface of the material was compressed and timed with a medical gauze, and the complete cessation time of bleeding was recorded as 125 seconds.

Example 3

(1) Preparing attapulgite nanorods:

weighing 5.0g of crude ore attapulgite subjected to grinding, washing and centrifuging, adding 500mL of deionized water, and ultrasonically crushing for 2h under 1500W power to obtain attapulgite nanorods with average length below 2 μm.

(2) The preparation of the attapulgite modified hemostatic material comprises the following steps:

dissolving 1.0g of polyvinylpyrrolidone in 10mL of absolute ethyl alcohol, adding 1.50g of attapulgite nanorods, and stirring for 36h in water bath at normal temperature; the rotating speed of a roller is set to be 500r/min, the distance between a needle head and the roller is 21cm, the liquid outlet speed is 0.05mL/min, the voltage of a positive electrode is 10kV, and the voltage of a negative electrode is 2kV in electrostatic spinning. The obtained attapulgite modified hemostatic material has SEM spectrum shown in figure 2: the hemostatic material is a film structure with a rough surface, the film takes the combination of attapulgite after partial rod crystal beam dissociation and polyvinylpyrrolidone through electrostatic action as a film main body, the attapulgite after partial rod crystal beam dissociation on the film surface is connected with the film through partial silicon hydroxyl, and the other part of the attapulgite is exposed outside to form the structure with the rough surface and play roles of hemostasis and hydrophilicity; the nano attapulgite is dispersed attapulgite nano particles; the dissociation of the attapulgite partial rod crystal beam is a phenomenon generated by ultrasonic crushing, grinding and freeze drying during pretreatment.

(3) Hemostasis test:

rats were anesthetized with 10% chloral hydrate (0.3ml/100g) by intraperitoneal injection, fixed in the supine position, sterilized, and the skin, muscle and peritoneum were cut layer by layer to expose the liver, taking the median incision of the abdomen about 5cm long. After the right lobe of the liver was fully exposed, a 1X 1cm square was drawn with a sharp knife at the center to a depth of about 0.5 cm. Removing liver tissue in the boundary by using tissue scissors, and scraping the wound surface by using tissue forceps to ensure that the liver wound surface has obvious blood seepage. The hemostatic material prepared in example 2 was placed on the wound surface, fully covered and attached to the liver tissue, and the medical gauze was pressed and timed properly over the outer side of the wound surface of the material, and the complete cessation time of bleeding was recorded as 140 seconds.

Example 4

(1) Preparing kaolinite nanosheets:

10.0g of crude ore kaolinite which is ground, washed and centrifuged is weighed, and 90mL of dimethyl sulfoxide and 10mL of deionized water are added. Stirring at 70 deg.C for 36h to obtain kaolinite pillared solution. And ultrasonically crushing the kaolinite pillared solution for 2h under 1500W power to obtain the kaolinite nanosheet, wherein the average size is below 1 mu m.

(2) Preparation of the kaolinite modified hemostatic material:

dissolving 1.0g of polyvinylpyrrolidone in 10mL of absolute ethyl alcohol, adding 2.40g of kaolinite nanosheet, and stirring for 36h in water bath at normal temperature; and (3) carrying out electrostatic spinning, wherein the rotating speed of a roller is set to be 500r/min, the distance between a needle head and the roller is 21cm, the liquid outlet speed is 0.05mL/min, the positive voltage is 10kV, and the negative voltage is 2kV, so that the kaolin modified hemostatic material is prepared.

(3) Hemostasis test:

rats were anesthetized with 10% chloral hydrate (0.3ml/100g) by intraperitoneal injection, fixed in the supine position, sterilized, and the skin, muscle and peritoneum were cut layer by layer to expose the liver, taking the median incision of the abdomen about 5cm long. After the right lobe of the liver was fully exposed, a 1X 1cm square was drawn with a sharp knife at the center to a depth of about 0.5 cm. Removing liver tissue in the boundary by using tissue scissors, and scraping the wound surface by using tissue forceps to ensure that the liver wound surface has obvious blood seepage. The prepared hemostatic material is placed on the wound surface, the liver tissue is fully covered and attached, the medical gauze is properly pressed and timed on the wound surface on the outer side of the material, and the complete stop time of the bleeding is recorded as 100 seconds.

Comparative example 1

(1) Preparing a polyvinyl pyrrolidone electrostatic spinning film:

dissolving 1.0g of polyvinylpyrrolidone in 10mL of absolute ethyl alcohol, and stirring for 36 hours at normal temperature in a water bath; the rotating speed of a roller is set to be 500r/min, the distance between a needle head and the roller is 21cm, the liquid outlet speed is 0.05mL/min, the voltage of a positive electrode is 10kV, and the voltage of a negative electrode is 2kV in electrostatic spinning. The halloysite electrospun film is prepared, and the SEM spectrum is shown in figure 3: from fig. 3, it is known that the degree of shrinkage of the PVP film is large, and the PVP filaments are heavily polycondensed, resulting in almost complete disappearance of the pores in the film.

(2) Hemostasis test:

rats were anesthetized with 10% chloral hydrate (0.3ml/100g) by intraperitoneal injection, fixed in the supine position, sterilized, and the skin, muscle and peritoneum were cut layer by layer to expose the liver, taking the median incision of the abdomen about 5cm long. After the right lobe of the liver was fully exposed, a 1X 1cm square was drawn with a sharp knife at the center to a depth of about 0.5 cm. Removing liver tissue in the boundary by using tissue scissors, and scraping the wound surface by using tissue forceps to ensure that the liver wound surface has obvious blood seepage. The halloysite electrospun film prepared in comparative example 1 was placed on the wound surface, fully covered and attached to the liver tissue, and medical gauze was pressed and timed properly over the wound surface on the outer side of the material, and the complete cessation time of bleeding was recorded as 360 seconds.

While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims.

Claims (4)

1. The silicate clay modified hemostatic material is characterized in that the hemostatic material is formed by compounding silicate clay and high polymer through electrostatic spinning; the mass ratio of the silicate clay to the high polymer is 0.5-2.5: 1; the silicate clay comprises kaolinite, halloysite, attapulgite or montmorillonite; wherein, part of silicon hydroxyl of the silicate clay is combined with the hydrogen bond of the high polymer, and the rest silicon hydroxyl plays roles of hemostasis and hydrophily on the surface of the hemostatic material; the high polymer comprises polyvinylpyrrolidone, polyethylene, levorotatory polylactic acid, polyethylacrylate or polyvinyl alcohol;

the hemostatic material is a 3D net structure consisting of a plurality of fiber bundles, and the fiber bundles are formed by compounding nano halloysite and high polymers through electrostatic interaction;

the silicate clay is attapulgite, the attapulgite is dispersed attapulgite nano particles, and the hemostatic material is formed by compounding the dispersed attapulgite nano particles with a high polymer through electrostatic interaction;

the preparation method of the hemostatic material comprises the following steps:

(1) carrying out pretreatment and ultrasonic crushing on silicate clay;

the average particle size of the silicate clay after ultrasonic crushing is less than 1 mu m;

(2) dissolving the high polymer in ethanol to prepare a high polymer ethanol solution with the concentration of 0.1-0.3 g/mL;

(3) mixing the silicate clay treated in the step (1) with the high polymer ethanol solution obtained in the step (2) to obtain an electrostatic spinning solution;

wherein the mass ratio of the silicate clay to the high polymer is 0.5-2.5: 1;

(4) performing electrostatic spinning on the electrostatic spinning solution obtained in the step (3) to obtain a silicate clay modified hemostatic material;

wherein the silicate clay comprises kaolinite, halloysite, attapulgite or montmorillonite; the high polymer comprises polyvinylpyrrolidone, polyethylene, levorotatory polylactic acid, polyethylacrylate or polyvinyl alcohol;

the parameters of electrostatic spinning are as follows: the rotating speed of the roller is 450-500 r/min; the receiving distance is 17-21 cm; the voltage of the positive electrode is 10-12 kV; the voltage of the negative electrode is 2-3 kV;

wherein when the silicate clay is halloysite, attapulgite or montmorillonite, the pretreatment comprises grinding, washing and centrifuging;

when the silicate clay is kaolinite, the pretreatment comprises grinding, washing, centrifuging and pillaring treatment;

wherein the pillared liquid used for pillared treatment is dimethyl sulfoxide aqueous solution.

2. The method for preparing the silicate clay modified hemostatic material according to claim 1, comprising the steps of:

(1) carrying out pretreatment and ultrasonic crushing on silicate clay;

the average particle size of the silicate clay after ultrasonic crushing is less than 1 mu m;

(2) dissolving the high polymer in ethanol to prepare a high polymer ethanol solution with the concentration of 0.1-0.3 g/mL;

(3) mixing the silicate clay treated in the step (1) with the high polymer ethanol solution obtained in the step (2) to obtain an electrostatic spinning solution;

wherein the mass ratio of the silicate clay to the high polymer is 0.5-2.5: 1;

(4) performing electrostatic spinning on the electrostatic spinning solution obtained in the step (3) to obtain a silicate clay modified hemostatic material;

wherein the silicate clay comprises kaolinite, halloysite, attapulgite or montmorillonite; the high polymer comprises polyvinylpyrrolidone, polyethylene, levorotatory polylactic acid, polyethylacrylate or polyvinyl alcohol;

the parameters of electrostatic spinning are as follows: the rotating speed of the roller is 450-500 r/min; the receiving distance is 17-21 cm; the voltage of the positive electrode is 10-12 kV; the voltage of the negative electrode is 2-3 kV;

wherein when the silicate clay is halloysite, attapulgite or montmorillonite, the pretreatment comprises grinding, washing and centrifuging;

when the silicate clay is kaolinite, the pretreatment comprises grinding, washing, centrifuging and pillaring treatment;

wherein the pillared liquid used for pillared treatment is dimethyl sulfoxide aqueous solution.

3. The preparation method according to claim 2, wherein the ultrasonication power is 400-800W and the time is 100-150 min.

4. The method according to claim 2, wherein the liquid discharge rate of the electrostatic spinning is 0.05 mL/min.

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