CN117919485A - Hemostatic and antibacterial medical material and preparation method thereof - Google Patents
Hemostatic and antibacterial medical material and preparation method thereof Download PDFInfo
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- Materials For Medical Uses (AREA)
Abstract
The invention discloses a hemostatic and antibacterial medical material and a preparation method thereof, and relates to the technical field of medical materials; the hemostatic and antibacterial medical material consists of synergistic gel microspheres and a hydrogel substrate; the synergistic gel microsphere consists of sodium alginate, carboxymethyl cellulose, tamarind polysaccharide and tannic acid; the hydrogel substrate consists of hyaluronic acid, water-soluble silk fibroin and calcium chloride; the synergistic gel microspheres are embedded into the hydrogel matrix, and the formed multi-stage gel structure has high porosity and huge surface area, so that the physical barrier is tighter and more complex, bacteria are better isolated, adhered and killed, the efficient antibacterial effect is achieved, the gel system has stronger adhesiveness and adsorption effect, and the bleeding stopping effect can be better exerted.
Description
Technical Field
The invention belongs to the technical field of medical materials, and particularly relates to a hemostatic and antibacterial medical material and a preparation method thereof.
Background
The high molecular biological material is used in the field of medical appliances such as uterine cavity expanding devices and the like due to the unique chemical and physical properties such as good biocompatibility, simulation property, strong plasticity and the like, thereby being beneficial to producing better hemostasis or other medical application effects; however, the high molecular biological material has certain microbial affinity, so that microorganisms are easy to adhere to the surface of medical equipment, bacterial films are formed on the surface of the material after the microorganisms are gradually propagated, and the iatrogenic infection problem caused by pathogenic bacteria becomes one of the hidden dangers with the greatest threat to the health of patients, thereby seriously endangering the public health safety of society.
The current treatment methods commonly used in clinic are sterilization or antibiotics before the medical devices are used, which still can cause unavoidable damage to human bodies and induce bacteria to generate drug resistance; with the continuous progress of medical science and technology and the increasing attention of people on sanitation and safety, the application of the antibacterial medical material on medical instruments is paid attention to, and the antibacterial medical material is coated on the surfaces of the medical instruments, so that bacteria and other pathogenic bacteria attached to the surfaces can be effectively killed and inhibited, the infection risk caused by the medical instruments is reduced, and the treatment effect and the life quality of patients are improved.
The prior art mainly has the following problems:
The surfaces of medical instruments such as the uterine cavity expanding device are easy to be polluted by bacteria, so that the inside or the inside of the uterine cavity is infected by bacteria, and then inflammation is caused, and the medical effect is adversely affected.
Disclosure of Invention
Aiming at the situation, in order to overcome the defects of the prior art, the invention provides a hemostatic and antibacterial medical material which comprises the following components in parts by weight: 50-60 parts of synergistic gel microsphere and 20-30 parts of hydrogel substrate.
The synergistic gel microsphere comprises the following components in parts by weight: 10-20 parts of sodium alginate, 2-4 parts of carboxymethyl cellulose, 5-8 parts of tamarind polysaccharide and 2-5 parts of tannic acid.
The hydrogel substrate comprises the following components in parts by weight: 10-15 parts of hyaluronic acid, 8-10 parts of water-soluble silk fibroin and 3-5 parts of calcium chloride.
The preparation method of the synergistic gel microsphere specifically comprises the following steps:
(1) Drying tamarind seeds at 140-150 ℃ for 5-7h, removing shells, drying at high temperature to facilitate the shelling treatment, crushing the obtained tamarind seeds, putting 1-3g into 200mL of water for extraction at 80-90 ℃ for 40-50min, standing the obtained extract for 12-24h to facilitate protein precipitation, optimizing the extraction purity, separating the extract into two layers after standing, centrifuging the upper layer, centrifuging at 1000-2000rpm for 10-15min, removing impurities to obtain a supernatant, performing filter pressing on the lower layer, removing protein to obtain a filtrate, merging the colloid 1 and the colloid 2 to obtain a total colloid, adding 1-2 times of ethanol solution with the volume fraction of 75-95%, standing for 2-4h after stirring, centrifuging at 1000-2000rpm for 10-15min, collecting precipitates, obtaining high-purity, stable and gelifiable extract, drying, crushing, sieving with 100-200 meshes to obtain fine powder of polysaccharide, and obtaining fine powder of polysaccharide of 0.6-1.8 g;
(2) Dissolving sodium alginate and carboxymethyl cellulose in 2000mL of water, stirring at 100-300rpm for 6-8h, wherein the sodium alginate and the carboxymethyl cellulose can be combined under the action of electrostatic attraction and the like to obtain composite sol;
(3) Dissolving the tamarind seed polysaccharide in 80mL of water to obtain a tamarind seed polysaccharide solution for later use, wherein the tamarind seed polysaccharide solution can be used for increasing the antibacterial property and the tackiness of the microspheres prepared later, then adopting an electrospraying device to electrospray the composite sol in the step (2) into a receiving device containing the tamarind seed polysaccharide solution, and preparing the composite microspheres with the average particle size of 400-800 mu m by using the electrostatic acting force of high-voltage static on the polymer solution through an electrospraying method, stirring for 30-40min at the speed of 100-300rpm, and filtering to obtain gel microspheres;
(4) Dissolving tannic acid in 50mL of water, wherein the tannic acid is used as an effective cross-linking agent, so that the stability and the adhesiveness of the gel microspheres can be enhanced, the antibacterial and hemostatic effects of the gel microspheres can be enhanced, and the tannic acid solution can be obtained by uniformly stirring;
(5) Adding the gel microsphere in the step (3) into the tannic acid solution in the step (4), regulating the pH to 4-5, crosslinking at 45-55 ℃ for 2-3h, filtering, washing the obtained crosslinked gel microsphere to be neutral by deionized water, and drying at 50-60 ℃ for 5-6h to obtain the synergistic gel microsphere;
preferably, in the step (1), in the drying process, the drying temperature is 80-100 ℃, the drying time is 2-4 hours, the gelation of the extract is affected by the too high temperature, and the extraction efficiency is not good;
preferably, in the step (2), the mass fraction of sodium alginate and carboxymethyl cellulose in the composite sol is 1-3%;
Preferably, in the step (3), the mass fraction of tamarind seed polysaccharide in the tamarind seed polysaccharide solution is 10-20%;
Preferably, in the step (3), in the process of electronic spraying, the environment temperature is 20-30 ℃, the voltage is 8-10kV, the propulsion rate is 10-30 mu L/min, the receiving distance is 10-15cm, the stainless steel spray head is a needle head with the number of 4-6, and the process can be used for preparing high-purity microspheres simply and easily;
preferably, in the step (4), the tannic acid solution has a mass fraction of tannic acid of 5 to 15%.
The invention also provides a preparation method of the hemostatic and antibacterial medical material, which comprises the following steps:
S1, dissolving hyaluronic acid in 1000mL of water, adding water-soluble silk fibroin, stirring uniformly to form fluffy porous hydrogel, adding calcium chloride for crosslinking, and adding a crosslinking agent to increase the stability of the porous hydrogel to obtain a hydrogel substrate;
S2, adding the synergistic gel microspheres into the hydrogel substrate in the step S1, and uniformly dispersing the synergistic gel microspheres by ultrasonic waves, so that the porosity and the surface area of the hydrogel are improved, the antibacterial and hemostatic effects are effectively and stably exerted, and the hemostatic and antibacterial medical material is obtained;
Preferably, in the step S1, calcium chloride can be combined with hydroxyl or carboxyl in hyaluronic acid and water-soluble silk fibroin in the crosslinking process, the temperature is controlled to be 45-60 ℃, the stirring speed is 300-500rpm, and the stirring time is 50-60min;
Preferably, in the step S2, in the ultrasonic dispersion process, the ultrasonic power is 500-600W, and the ultrasonic time is 20-30min, so that the uniform dispersion of the embedded hydrogel substrate of the gel microsphere is facilitated.
The beneficial effects obtained by the invention are as follows:
According to the invention, the synergistic gel microspheres are embedded into the hydrogel substrate, so that the adhesiveness of medical materials is obviously improved, and the antibacterial and hemostatic effects are excellent; in the synergistic gel microsphere, sodium alginate, carboxymethyl cellulose, tamarind polysaccharide and tannic acid are crosslinked to form a porous gel microsphere, so that the porous gel microsphere has excellent adhesiveness, the bacteria can be prevented from diffusing and propagating through a formed viscous physical barrier, and can be adhered to the surface of the barrier, and the antibacterial property of the component substances can destroy the thallus structure, block nutrition absorption, generate strong antibacterial effect for killing and inhibiting, and simultaneously, the gel microsphere has a complex porous structure, can adsorb a large amount of fibrinogen, quickly form thrombus to realize hemostatic effect, and the viscous gel system can accelerate the coagulation of platelets to form a hypertonic environment, slow the speed and flow of blood flowing outwards in wounds and realize high-efficiency hemostatic effect; the tamarind polysaccharide endows the gel microsphere with spectral antibacterial property, enhances the antibacterial effect, and has stronger adhesiveness through crosslinking modification of the tamarind polysaccharide and tannic acid, the tannic acid can also interact with blood through phenolic hydroxyl groups to promote blood coagulation, the synergistic antibacterial and hemostatic effects are achieved, and the carboxymethyl cellulose contains acidic carboxyl functional groups and can be combined with Fe 3+ ions in hemoglobin, so that the end of capillary blood vessels can be closed and hemostasis is facilitated; the synergistic gel microspheres are embedded into the hydrogel matrix, and the formed multi-stage gel structure has high porosity and huge surface area, so that the physical barrier is tighter and more complex, bacteria are better isolated, adhered and killed, the efficient antibacterial effect is achieved, the gel system has stronger adhesiveness and adsorption effect, and the bleeding stopping effect can be better exerted; the medical hemostatic and antibacterial material is prepared from the synergistic gel microspheres and the hydrogel substrate, has a highly complex multi-layer gel structure with porous and surface areas, remarkably enhances the adhesiveness, and has high-efficiency antibacterial and hemostatic effects.
Drawings
FIG. 1 is a scanning electron microscope image of the synergistic gel microsphere prepared in example 1 of the present invention;
FIG. 2 is a graph showing the results of the bond strength of examples 1-4 and comparative examples 1-3 of the present invention;
FIG. 3 is a graph showing the results of the diameter of the inhibition zone of examples 1-4 and comparative examples 1-3 according to the present invention;
FIG. 4 is a graph showing the results of hemostasis time for examples 1-4 and comparative examples 1-3 of the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention; all other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the present application. The preferred methods and materials described herein are illustrative only and should not be construed as limiting the application.
The experimental methods in the following examples are all conventional methods unless otherwise specified; the test materials used in the examples described below, unless otherwise specified, were purchased from commercial sources.
The sources of reagents used in the examples are as follows:
sodium alginate CASNo 9005-38-3, brand Innochem, cat# A02570;
Carboxymethyl cellulose CASNo 9004-32-4, brand Innochem, cat# A05925;
Tannic acid CASNo 1401-55-4, brand Innochem, product number A38870;
Hyaluronic acid CASNo 9004-61-9, brand Apinno, cat# GC36971;
Water-soluble silk fibroin brand Aladin, cat# W293432-500mg;
calcium chloride CASNo 10043-52-4, brand Innochem, cat# A01289;
absolute ethyl alcohol CASNo, 64-17-5, brand Innochem, product number G00004.
Example 1
The embodiment provides a hemostatic and antibacterial medical material, which comprises the following components in parts by weight: 60 parts of synergistic gel microsphere and 30 parts of hydrogel substrate.
The synergistic gel microsphere comprises the following components in parts by weight: 20 parts of sodium alginate, 4 parts of carboxymethyl cellulose, 8 parts of tamarind polysaccharide and 5 parts of tannic acid.
The hydrogel substrate comprises the following components in parts by weight: 15 parts of hyaluronic acid, 10 parts of water-soluble silk fibroin and 5 parts of calcium chloride.
The preparation method of the synergistic gel microsphere specifically comprises the following steps:
(1) Drying tamarind seeds at 150 ℃ for 7 hours, removing shells, drying at high temperature to facilitate the shelling treatment, crushing the obtained tamarind seeds by a 60-mesh screen, placing 3g in 200mL of water for extraction at 90 ℃ for 50 minutes, standing the obtained extract for 24 hours, settling to facilitate protein precipitation, optimizing the extraction purity, separating the extract into two layers after standing, centrifuging the upper layer at 2000rpm, centrifuging for 15 minutes, removing impurities to obtain a supernatant, obtaining a glue solution 1, performing filter pressing on the lower layer, removing protein to obtain a filtrate, obtaining a glue solution 2, combining the glue solution 1 and the glue solution 2 to obtain a total glue solution, adding 2 times of ethanol solution with 95% volume fraction, standing for 4 hours after stirring, centrifuging at 2000rpm, centrifuging for 15 minutes, collecting precipitates, obtaining an extract with high purity, stability and excellent gelation property, drying, wherein in the drying process, the drying temperature is 90 ℃ for 4 hours, the gelation property of the extract is affected excessively low, the extraction efficiency is not facilitated, crushing is performed, and the glue solution is filtered, and the glue solution is obtained by 200 meshes, obtaining fine powder, namely, the tamarind polysaccharide is obtained;
(2) Dissolving sodium alginate and carboxymethyl cellulose in 2000mL of water, wherein the mass fraction of the sodium alginate and the carboxymethyl cellulose is 3%, stirring, the stirring speed is 300rpm, the stirring time is 8 hours, and the sodium alginate and the carboxymethyl cellulose can be combined under the actions of electrostatic attraction and the like to obtain composite sol;
(3) Dissolving the tamarind polysaccharide in 80mL of water to obtain a tamarind polysaccharide solution with the mass fraction of 20% for later use, wherein the tamarind polysaccharide solution can be used for increasing the antibacterial property and the tackiness of the microspheres prepared later, then adopting an electrospraying device to electrospray the composite sol in the step (2) into a receiving device containing the tamarind polysaccharide solution, wherein the environmental temperature is 30 ℃, the voltage is 10kV, the propelling speed is 30 mu L/min, the receiving distance is 15cm, a stainless steel spray head is a 10-gauge needle head, the process can be used for simply and easily preparing high-purity microspheres, the electrospraying method utilizes the electrostatic force of high-voltage static electricity on the polymer solution to prepare composite microspheres with the average particle diameter of 800 mu m, stirring at the speed of 300rpm for 40min, and filtering to obtain gel microspheres;
(4) Dissolving tannic acid in 50mL of water, wherein the mass fraction of the tannic acid is 15%, and the tannic acid is used as an effective cross-linking agent, so that the stability and the adhesiveness of the gel microspheres can be enhanced, the antibacterial and hemostatic effects of the gel microspheres can be enhanced, and the tannic acid solution can be obtained by uniformly stirring;
(5) And (3) adding the gel microspheres in the step (3) into the tannic acid solution in the step (4), regulating the pH to 5, crosslinking at 55 ℃ for 3 hours, filtering, washing the obtained crosslinked gel microspheres with deionized water to be neutral, drying at 60 ℃ for 6 hours, and obtaining the synergistic gel microspheres.
The embodiment provides a preparation method of a hemostatic and antibacterial medical material, which specifically comprises the following steps:
S1, dissolving hyaluronic acid in 1000mL of water, adding water-soluble silk fibroin, stirring uniformly to form fluffy porous hydrogel, adding calcium chloride for crosslinking, wherein in the crosslinking process, the calcium chloride can be combined with hydroxyl or carboxyl in the hyaluronic acid and the water-soluble silk fibroin, the temperature is controlled to be 60 ℃, the stirring rotation speed is 500rpm, the stirring time is 60 minutes, and the addition of the crosslinking agent increases the stability of the porous hydrogel to obtain a hydrogel substrate;
S2, adding the synergistic gel microspheres into the hydrogel substrate in the step S1, uniformly dispersing by ultrasonic, wherein in the ultrasonic dispersing process, the ultrasonic power is 600W, and the ultrasonic time is 30min, so that the uniform dispersion of the embedded hydrogel substrate of the synergistic gel microspheres is facilitated, the porosity and the surface area of the hydrogel are facilitated to be better increased, the antibacterial and hemostatic effects are conveniently and efficiently exerted, and the hemostatic and antibacterial medical material is obtained.
In this example, a scanning electron microscope was used to observe the microscopic morphology of the synergistic gel microsphere prepared in this example, and fig. 1 is an SEM image of the synergistic gel microsphere prepared in example 1, which is 5 times magnified, as shown in the figure, and the synergistic gel microsphere prepared in this example is a gel microsphere with a porous structure.
Example 2
The embodiment provides a hemostatic and antibacterial medical material, which comprises the following components in parts by weight: 50 parts of synergistic gel microsphere and 20 parts of hydrogel substrate.
The synergistic gel microsphere comprises the following components in parts by weight: 10 parts of sodium alginate, 2 parts of carboxymethyl cellulose, 5 parts of tamarind polysaccharide and 2 parts of tannic acid.
The hydrogel substrate comprises the following components in parts by weight: 10 parts of hyaluronic acid, 8 parts of water-soluble silk fibroin and 3 parts of calcium chloride.
The preparation method of the synergistic gel microsphere specifically comprises the following steps:
(1) Drying tamarind seeds at 140 ℃ for 5 hours, removing shells, drying at high temperature to facilitate the shelling treatment, crushing the obtained tamarind seeds by a 40-mesh screen, placing 1g in 200mL of water for extraction at 80 ℃ for 40 minutes, standing the obtained extract for 12 hours, settling to facilitate protein precipitation, optimizing the extraction purity, separating the extract into two layers after standing, centrifuging the upper layer at 1000rpm, centrifuging for 10 minutes, removing impurities to obtain a supernatant, obtaining a glue solution 1, performing filter pressing on the lower layer, removing protein to obtain a filtrate, obtaining a glue solution 2, combining the glue solution 1 and the glue solution 2 to obtain a total glue solution, adding 1 time of ethanol solution with the volume fraction of 75%, standing for 2 hours after stirring, centrifuging at 1000rpm, centrifuging for 10 minutes, collecting precipitates, obtaining an extract with high purity, stability and excellent gelation property, drying, wherein the drying temperature is 80 ℃ in the drying process, the gelation property of the extract is influenced by the too high temperature, the extraction efficiency is not influenced, the fine powder is crushed, and the fine powder is obtained by 100 meshes of the screen;
(2) Dissolving sodium alginate and carboxymethyl cellulose in 2000mL of water, wherein the mass fraction of the sodium alginate and the carboxymethyl cellulose is 1%, stirring at 100rpm for 6 hours, and combining the sodium alginate and the carboxymethyl cellulose under the action of electrostatic attraction to obtain composite sol;
(3) Dissolving the tamarind polysaccharide in 80mL of water to obtain a tamarind polysaccharide solution with the mass fraction of 10% for later use, wherein the tamarind polysaccharide solution can be used for increasing the antibacterial property and the tackiness of the microspheres prepared later, then adopting an electrospraying device to electrospray the composite sol in the step (2) into a receiving device containing the tamarind polysaccharide solution, wherein the environmental temperature is 20 ℃, the voltage is 8kV, the propelling speed is 10 mu L/min, the receiving distance is 10cm, a stainless steel spray head is a needle with the size of 4, the process can be used for simply and easily preparing high-purity microspheres, the electrospraying method utilizes the electrostatic force of high-voltage static electricity on the polymer solution to prepare composite microspheres with the average particle size of 400 mu m, stirring at the speed of 100rpm for 30min, and filtering to obtain gel microspheres;
(4) Dissolving tannic acid in 50mL of water, wherein the mass fraction of the tannic acid is 5%, and the tannic acid is used as an effective cross-linking agent, so that the stability and the adhesiveness of the gel microspheres can be enhanced, the antibacterial and hemostatic effects of the gel microspheres can be enhanced, and the tannic acid solution can be obtained by uniformly stirring;
(5) Adding the gel microsphere in the step (3) into the tannic acid solution in the step (4), regulating the pH to 4, crosslinking at 45 ℃ for 2 hours, filtering, washing the obtained crosslinked gel microsphere with deionized water to be neutral, drying at 50 ℃ for 5 hours, and obtaining the synergistic gel microsphere.
The embodiment provides a preparation method of a hemostatic and antibacterial medical material, which specifically comprises the following steps:
s1, dissolving hyaluronic acid in 1000mL of water, adding water-soluble silk fibroin, stirring uniformly to form fluffy porous hydrogel, adding calcium chloride for crosslinking, wherein in the crosslinking process, the calcium chloride can be combined with hydroxyl or carboxyl in the hyaluronic acid and the water-soluble silk fibroin, the temperature is controlled to be 45 ℃, the stirring rotation speed is 300rpm, the stirring time is 50min, and the addition of the crosslinking agent increases the stability of the porous hydrogel to obtain a hydrogel substrate;
S2, adding the synergistic gel microspheres into the hydrogel substrate in the step S1, and uniformly dispersing by ultrasonic, wherein in the ultrasonic dispersing process, the ultrasonic power is 500W, and the ultrasonic time is 20min, so that the uniform dispersion of the embedded hydrogel substrate of the synergistic gel microspheres is facilitated, the porosity and the surface area of the hydrogel are increased better, the antibacterial and hemostatic effects are conveniently and efficiently exerted, and the hemostatic and antibacterial medical material is obtained.
Example 3
The embodiment provides a hemostatic and antibacterial medical material, which comprises the following components in parts by weight: 55 parts of synergistic gel microsphere and 25 parts of hydrogel substrate.
The synergistic gel microsphere comprises the following components in parts by weight: 15 parts of sodium alginate, 3 parts of carboxymethyl cellulose, 6.5 parts of tamarind polysaccharide and 3.5 parts of tannic acid.
The hydrogel substrate comprises the following components in parts by weight: 12.5 parts of hyaluronic acid, 9 parts of water-soluble silk fibroin and 4 parts of calcium chloride.
The preparation method of the synergistic gel microsphere specifically comprises the following steps:
(1) Drying tamarind seeds at 145 ℃ for 6 hours, removing shells, drying at high temperature to facilitate the shelling treatment, crushing the obtained tamarind seeds by a 50-mesh screen, placing 2g in 200mL of water for extraction at 85 ℃ for 45 minutes, standing the obtained extract for 18 hours, settling to facilitate protein precipitation, optimizing the extraction purity, separating the extract into two layers after standing, centrifuging the upper layer, centrifuging at 1500rpm for 12.5 minutes, removing impurities to obtain a supernatant, obtaining a glue solution 1, performing filter pressing on the lower layer, removing protein to obtain a filtrate, obtaining a glue solution 2, combining the glue solution 1 and the glue solution 2 to obtain a total glue solution, adding 1.5 times of an ethanol solution with a volume fraction of 85%, standing for 3 hours after stirring, centrifuging at 1500rpm for 12.5 minutes, collecting precipitate, drying, and obtaining an extract with high purity, stability and gelation property, wherein the drying temperature is 85 ℃ for 3 hours, the gelation property of the extract is influenced by the too high temperature, the too low gelation property is not beneficial to the extraction efficiency, crushing, and passing through 150 meshes, obtaining fine powder, and obtaining tamarind polysaccharide by 1.2 g;
(2) Dissolving sodium alginate and carboxymethyl cellulose in 2000mL of water, wherein the mass fraction of the sodium alginate and the carboxymethyl cellulose is 2%, stirring, the stirring speed is 200rpm, the stirring time is 7h, and the sodium alginate and the carboxymethyl cellulose can be combined under the actions of electrostatic attraction and the like to obtain composite sol;
(3) Dissolving the tamarind polysaccharide in 80mL of water to obtain a tamarind polysaccharide solution with the mass fraction of 15% for later use, wherein the tamarind polysaccharide solution can be used for increasing the antibacterial property and the tackiness of the microspheres prepared later, then adopting an electrospraying device to electrospray the composite sol in the step (2) into a receiving device containing the tamarind polysaccharide solution, wherein the environmental temperature is 25 ℃, the voltage is 9kV, the propelling speed is 20 mu L/min, the receiving distance is 12.5cm, a stainless steel nozzle is a 7-gauge needle, the process can be used for simply and easily preparing high-purity microspheres, the electrospraying method utilizes the electrostatic force of high-voltage static electricity on the polymer solution to prepare composite microspheres with the average particle diameter of 600 mu m, stirring for 35min at the speed of 200rpm, and filtering to obtain gel microspheres;
(4) Dissolving tannic acid in 50mL of water, wherein the mass fraction of the tannic acid is 10%, and the tannic acid is used as an effective cross-linking agent, so that the stability and the adhesiveness of the gel microspheres can be enhanced, the antibacterial and hemostatic effects of the gel microspheres can be enhanced, and the tannic acid solution can be obtained by uniformly stirring;
(5) Adding the gel microsphere in the step (3) into the tannic acid solution in the step (4), regulating the pH to 4.5, crosslinking at 50 ℃ for 2.5 hours, filtering, washing the obtained crosslinked gel microsphere with deionized water to be neutral, and drying at 55 ℃ for 5.5 hours to obtain the synergistic gel microsphere.
The embodiment provides a preparation method of a hemostatic and antibacterial medical material, which specifically comprises the following steps:
s1, dissolving hyaluronic acid in 1000mL of water, adding water-soluble silk fibroin, stirring uniformly to form fluffy porous hydrogel, adding calcium chloride for crosslinking, wherein in the crosslinking process, the calcium chloride can be combined with hydroxyl or carboxyl in the hyaluronic acid and the water-soluble silk fibroin, the temperature is controlled to be 52.5 ℃, the stirring rotation speed is 400rpm, the stirring time is 55min, and the addition of the crosslinking agent increases the stability of the porous hydrogel to obtain a hydrogel substrate;
S2, adding the synergistic gel microspheres into the hydrogel substrate in the step S1, and uniformly dispersing by ultrasonic, wherein in the ultrasonic dispersing process, the ultrasonic power is 550W, and the ultrasonic time is 25min, so that the uniform dispersion of the embedded hydrogel substrate of the synergistic gel microspheres is facilitated, the porosity and the surface area of the hydrogel are increased better, the antibacterial and hemostatic effects are conveniently and efficiently exerted, and the hemostatic and antibacterial medical material is obtained.
Example 4
The embodiment provides a hemostatic and antibacterial medical material, which comprises the following components in parts by weight: 60 parts of synergistic gel microspheres and 20 parts of hydrogel substrate.
The synergistic gel microsphere comprises the following components in parts by weight: 10 parts of sodium alginate, 2 parts of carboxymethyl cellulose, 5 parts of tamarind polysaccharide and 2 parts of tannic acid.
The hydrogel substrate comprises the following components in parts by weight: 10 parts of hyaluronic acid, 8 parts of water-soluble silk fibroin and 3 parts of calcium chloride.
The preparation method of the synergistic gel microsphere specifically comprises the following steps:
(1) Drying tamarind seeds at 150 ℃ for 5 hours, removing shells, drying at high temperature to facilitate the shelling treatment, crushing the obtained tamarind seeds by a 60-mesh screen, placing 3g in 200mL of water for extraction at 90 ℃ for 40 minutes, standing the obtained extract for 12 hours, settling to facilitate protein precipitation, optimizing the extraction purity, separating the extract into two layers after standing, centrifuging the upper layer at 2000rpm, centrifuging for 10 minutes, removing impurities to obtain a supernatant, obtaining a colloid solution 1, performing filter pressing on the lower layer, removing protein to obtain a filtrate, obtaining a colloid solution 2, combining the colloid solution 1 and the colloid solution 2 to obtain a total colloid solution, adding 2 times of ethanol solution with 95% volume fraction, standing for 2 hours after stirring, centrifuging at 2000rpm, centrifuging for 10 minutes, collecting precipitates, obtaining an extract with high purity, stability and excellent gelation property, drying, wherein in the drying process, the drying temperature is 90 ℃ for 2 hours, the gelation property of the extract is affected excessively low, the extraction efficiency is not facilitated, crushing is performed, and the colloid solution is obtained by sieving with 200 meshes, and obtaining fine powder, namely 1.8g tamarind polysaccharide;
(2) Dissolving sodium alginate and carboxymethyl cellulose in 2000mL of water, wherein the mass fraction of the sodium alginate and the carboxymethyl cellulose is 3%, stirring at 300rpm for 6 hours, and combining the sodium alginate and the carboxymethyl cellulose under the action of electrostatic attraction to obtain composite sol;
(3) Dissolving the tamarind polysaccharide in 80mL of water to obtain a tamarind polysaccharide solution with the mass fraction of 18% for later use, wherein the tamarind polysaccharide solution can be used for increasing the antibacterial property and the tackiness of the microspheres prepared later, then adopting an electrospraying device to electrospray the composite sol in the step (2) into a receiving device containing the tamarind polysaccharide solution, wherein the environmental temperature is 30 ℃, the voltage is 10kV, the propelling speed is 30 mu L/min, the receiving distance is 15cm, a stainless steel spray head is a 10-gauge needle head, the process can be used for simply and easily preparing high-purity microspheres, the electrospraying method utilizes the electrostatic force of high-voltage static electricity on the polymer solution to prepare composite microspheres with the average particle diameter of 800 mu m, stirring at the speed of 300rpm for 30min, and filtering to obtain gel microspheres;
(4) Dissolving tannic acid in 50mL of water, wherein the mass fraction of the tannic acid is 15%, and the tannic acid is used as an effective cross-linking agent, so that the stability and the adhesiveness of the gel microspheres can be enhanced, the antibacterial and hemostatic effects of the gel microspheres can be enhanced, and the tannic acid solution can be obtained by uniformly stirring;
(5) And (3) adding the gel microspheres in the step (3) into the tannic acid solution in the step (4), regulating the pH to 5, crosslinking at 55 ℃ for 2 hours, filtering, washing the obtained crosslinked gel microspheres with deionized water to be neutral, drying at 60 ℃ for 5 hours, and obtaining the synergistic gel microspheres.
The embodiment provides a preparation method of a hemostatic and antibacterial medical material, which specifically comprises the following steps:
S1, dissolving hyaluronic acid in 1000mL of water, adding water-soluble silk fibroin, stirring uniformly to form fluffy porous hydrogel, adding calcium chloride for crosslinking, wherein in the crosslinking process, the calcium chloride can be combined with hydroxyl or carboxyl in the hyaluronic acid and the water-soluble silk fibroin, the temperature is controlled to be 60 ℃, the stirring rotation speed is 500rpm, the stirring time is 50min, and the addition of the crosslinking agent increases the stability of the porous hydrogel to obtain a hydrogel substrate;
S2, adding the synergistic gel microspheres into the hydrogel substrate in the step S1, uniformly dispersing by ultrasonic, wherein in the ultrasonic dispersing process, the ultrasonic power is 600W, and the ultrasonic time is 20min, so that the uniform dispersion of the embedded hydrogel substrate of the synergistic gel microspheres is facilitated, the porosity and the surface area of the hydrogel are facilitated to be better increased, the antibacterial and hemostatic effects are conveniently and efficiently exerted, and the hemostatic and antibacterial medical material is obtained.
Comparative example 1
This comparative example provides a hemostatic and antibacterial medical material, which is different from example 1 in that synergistic gel microspheres are not contained in the hemostatic and antibacterial medical material; the preparation method of the hemostatic and antibacterial medical material is the same as that of the example 1.
Comparative example 2
This comparative example provides a hemostatic and antibacterial medical material which is different from example 1 in that the synergistic gel microspheres do not contain tamarind polysaccharide; the preparation method of the synergistic gel microsphere does not comprise the step (1); the preparation method of the hemostatic and antibacterial medical material is the same as that of the example 1.
Comparative example 3
This comparative example provides a hemostatic and antibacterial medical material, which is different from example 1 in that a hydrogel substrate is not included in the hemostatic and antibacterial medical material; the preparation method of the synergistic gel microsphere is the same as that of the example 1; the preparation method of the hemostatic and antibacterial medical material does not comprise the step S1.
Experimental example 1
Adhesion experiments:
Test sample: hemostatic and antibacterial medical materials prepared in examples 1 to 4 and comparative examples 1 to 3.
The testing method comprises the following steps: the adhesion performance of the test specimens was tested using lap shear with pigskin as a substrate, fresh pigskin was cut into rectangles (50 mm. Times.10 mm) for use, the test specimens were transferred to the pigskin and adhered uniformly, the adhesion area was 4cm 2, pressed with a weight of 500g for 24 hours, and then the adhesive strength (KPa) was measured with a universal tester at a tensile rate of 5 mm/min.
FIG. 2 is a graph showing the results of the bond strengths of examples 1-4 and comparative examples 1-3; as shown in the figure, the adhesive strength of examples 1-4 is 78-90KPa, indicating that the adhesion is relatively strong; the adhesive strength of comparative examples 1-3 was 55-68KPa, indicating weaker adhesion; the hemostatic and antibacterial medical material of comparative example 1 does not contain synergistic gel microspheres, and cannot be embedded into a hydrogel substrate to form a multi-stage gel structure, so that the adhesiveness is weaker; the synergistic gel microsphere of comparative example 2 does not contain tamarind polysaccharide, cannot interact with hydroxyl groups or other functional groups of other substances, cannot form a more compact network structure, and cannot enhance the intermolecular adhesion, so that the adhesion is weaker; the hemostatic and antibacterial medical material of comparative example 3 does not contain a hydrogel substrate, which weakens the adhesiveness of the gel system, and thus results in weaker adhesiveness.
Experimental example 2
Antibacterial experiments:
Test sample: hemostatic and antibacterial medical materials prepared in examples 1 to 4 and comparative examples 1 to 3.
The testing method comprises the following steps: bacteria causing intrauterine infection are of various types, and common staphylococcus aureus and escherichia coli are selected as experimental bacteria for an antibacterial experiment in the experiment; preparing a test sample into a flat cylinder with the diameter of 12mm and the thickness of 2mm, placing the flat cylinder on an agar medium coated with 10 6 cfu/mL of bacteria liquid after ultraviolet sterilization, reversely buckling a culture dish, placing the culture dish in a constant-temperature incubator at 37 ℃ for culturing for 24 hours, taking out and observing the growth condition of a bacteriostasis ring, wherein the larger the diameter (mm) of the bacteriostasis ring is, the stronger the inhibition effect on experimental bacteria is.
FIG. 3 is a graph showing the results of the diameter of the inhibition zone for examples 1-4 and comparative examples 1-3; as shown in the figure, the diameters of the staphylococcus aureus and the escherichia coli inhibition zones of examples 1-4 are 40-50mm and 38-46mm respectively, and are all equal to or larger than 38, which shows that the antibacterial property is better; the diameters of the staphylococcus aureus and escherichia coli inhibition zones of comparative examples 1-3 are 17-28mm and 15-23mm respectively, which are less than or equal to 28, which indicates that the antibacterial property is general; the hemostatic and antibacterial medical material of the comparative example 1 does not contain synergistic gel microspheres, does not contain antibacterial sodium alginate, carboxymethyl cellulose, tamarind polysaccharide and tannic acid, cannot form a tighter and more complex physical barrier with a hydrogel substrate, weakens the antibacterial effect, and has smaller diameter of a bacteriostasis zone and general antibacterial property; the synergistic gel microsphere of the comparative example 2 does not contain tamarind polysaccharide, which has adverse effects on the spectrum antibacterial property and the adhesiveness of the gel microsphere, so that the antibacterial effect is weakened, and the diameter of a bacteriostasis ring is smaller, so that the antibacterial property is general; the medical material for hemostasis and antibiosis of the comparative example 3 does not contain a hydrogel substrate, weakens the tightness and the adhesiveness of a physical barrier of a gel system, cannot exert synergistic antibiosis effect with the synergistic gel microspheres, further weakens antibiosis effect, and leads to smaller diameter of a bacteriostasis ring and general antibiosis.
Experimental example 3
Hemostatic effect experiment:
Test sample: hemostatic and antibacterial medical materials prepared in examples 1 to 4 and comparative examples 1 to 3.
The testing method comprises the following steps: selecting 35 rabbits (weight 3-3.5 kg), randomly dividing into 7 groups of 5 rabbits each; and cutting off one quarter of the femoral artery of the left hind limb by each rabbit, completely smearing the test article to cover the bleeding part after 10s and 10s, and observing whether blood flows out or not after the simulated uterine cavity expansion device is attached to the test sample and pressed for 3-5s until the blood is completely coagulated, recording the hemostasis time(s), wherein the hemostasis time does not comprise the pressing time.
FIG. 4 is a graph showing the results of hemostasis time for examples 1-4 and comparative examples 1-3; as shown in the figure, the wound healing time of examples 1-4 is 10-17s, and the hemostatic time is shorter, which indicates that the hemostatic effect is better; the wound healing time of comparative examples 1-3 is 26-46s, the hemostatic time is longer, it is general to demonstrate hemostatic effect; the medical material for hemostasis and antibiosis of the comparative example 1 does not contain synergistic gel microspheres, does not have complex surface area and porous structure, can not adsorb a large amount of fibrinogen to rapidly stop bleeding, also weakens the viscosity of a gel system, further influences the hemostasis effect of a bleeding part, leads to longer hemostasis time, and indicates that the hemostasis effect is general; the synergistic gel microsphere of the comparative example 2 does not contain tamarind polysaccharide, so that the adhesiveness of the synergistic gel microsphere is weakened, the outward flow of blood in a wound is not facilitated to be slowed down, the hemostasis time is longer, and the general hemostasis effect is indicated; the medical material of the comparative example 3 does not contain a hydrogel substrate and does not contain a multi-stage gel structure, so that the adhesiveness and adsorption of a gel system are weakened, the hemostasis time is longer, and the general hemostasis effect is indicated.
The experimental results show that the adhesiveness, the antibacterial property and the hemostatic effect of the invention are obviously better than those of the samples of the comparative examples 1-3, wherein the adhesiveness of the example 1 using the synergistic gel microsphere is stronger, the antibacterial property is better, the hemostatic effect is better, the synergistic gel microsphere has a porous structure, a large amount of fibrinogen can be adsorbed, thrombus is rapidly formed, and the viscous gel system can accelerate the coagulation of platelets to form a hypertonic environment, slow down the outward flowing speed and flow of blood in wounds, and realize the efficient hemostatic effect; the synergistic gel microspheres are embedded into the hydrogel matrix, and the formed multi-stage gel structure has high porosity and huge surface area, so that the physical barrier is tighter and more complex, bacteria are better isolated, adhered and killed, the efficient antibacterial effect is achieved, the gel system has stronger adhesiveness and adsorption effect, and the bleeding stopping effect can be better exerted.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made hereto without departing from the spirit and principles of the present invention.
The invention and its embodiments have been described above with no limitation, and the invention is illustrated in the figures of the accompanying drawings as one of its embodiments, without limitation in practice. In summary, those skilled in the art, having benefit of this disclosure, will appreciate that the invention can be practiced without the specific details disclosed herein.
Claims (8)
1. A hemostatic and antibacterial medical material, which is characterized in that: the hemostatic and antibacterial medical material comprises the following components in parts by weight: 50-60 parts of synergistic gel microspheres and 20-30 parts of hydrogel substrate; the synergistic gel microsphere comprises the following components in parts by weight: 10-20 parts of sodium alginate, 2-4 parts of carboxymethyl cellulose, 5-8 parts of tamarind polysaccharide and 2-5 parts of tannic acid; the hydrogel substrate comprises the following components in parts by weight: 10-15 parts of hyaluronic acid, 8-10 parts of water-soluble silk fibroin and 3-5 parts of calcium chloride;
The preparation method of the synergistic gel microsphere specifically comprises the following steps:
(1) Drying tamarind seeds at 140-150 ℃ for 5-7h, removing shells, crushing the obtained tamarind seeds by a 40-60 mesh screen, placing 1-3g in 200mL of water for extraction at 80-90 ℃ for 40-50min, standing the obtained extract for 12-24h, separating the extract into two layers after standing, centrifuging the upper layer at 1000-2000rpm for 10-15min, removing impurities, taking supernatant to obtain a glue solution 1, performing filter pressing on the lower layer, removing proteins, taking filtrate to obtain a glue solution 2, combining the glue solution 1 and the glue solution 2 to obtain a total glue solution, adding 1-2 times of ethanol solution with the volume fraction of 75-95%, standing for 2-4h after stirring, centrifuging at 1000-2000rpm for 10-15min, collecting precipitate, drying, crushing, and screening with a 100-200 mesh screen to obtain fine powder of 0.6-1.8g to obtain tamarind polysaccharide;
(2) Dissolving sodium alginate and carboxymethyl cellulose in 2000mL of water, stirring at 100-300rpm for 6-8h to obtain composite sol;
(3) Dissolving the tamarind polysaccharide in 80mL of water to obtain a tamarind polysaccharide solution for later use, adopting an electrospray device to electrospray the composite sol in the step (2) into a receiving device containing the tamarind polysaccharide solution, preparing composite microspheres with average particle size of 400-800 mu m, stirring at a speed of 100-300rpm for 30-40min, and filtering to obtain gel microspheres;
(4) Dissolving tannic acid in 50mL of water, and uniformly stirring to obtain a tannic acid solution;
(5) Adding the gel microsphere in the step (3) into the tannic acid solution in the step (4), regulating the pH to 4-5, crosslinking at 45-55 ℃ for 2-3h, filtering, washing the obtained crosslinked gel microsphere to be neutral by deionized water, and drying at 50-60 ℃ for 5-6h to obtain the synergistic gel microsphere.
2. The hemostatic and antibacterial medical material according to claim 1 wherein: in the step (1), in the drying process, the drying temperature is 80-100 ℃ and the drying time is 2-4h.
3. The hemostatic and antibacterial medical material according to claim 2 wherein: in the step (2), the mass fraction of sodium alginate and carboxymethyl cellulose in the composite sol is 1-3%.
4. A hemostatic and antibacterial medical material according to claim 3 wherein: in the step (3), the mass fraction of tamarind polysaccharide in the tamarind polysaccharide solution is 10-20%; in the process of electric spraying, the ambient temperature is 20-30 ℃, the voltage is 8-10kV, the propelling speed is 10-30 mu L/min, the receiving distance is 10-15cm, and the stainless steel spray head is a needle head with a number of 4-10.
5. The hemostatic and antibacterial medical material according to claim 4 wherein: in the step (4), the mass fraction of tannic acid in the tannic acid solution is 5-15%.
6. A method for preparing a hemostatic and antibacterial medical material according to any one of claims 1-5, characterized in that: the method specifically comprises the following steps:
S1, dissolving hyaluronic acid in 1000mL of water, adding water-soluble silk fibroin, uniformly stirring, and then adding calcium chloride for crosslinking to obtain a hydrogel substrate;
S2, adding the synergistic gel microspheres into the hydrogel substrate in the step S1, and uniformly dispersing the synergistic gel microspheres by ultrasonic waves to obtain the hemostatic and antibacterial medical material.
7. The method for preparing the hemostatic and antibacterial medical material according to claim 6, wherein the method comprises the following steps: in the step S1, the temperature is controlled to be 45-60 ℃ and the stirring speed is 300-500rpm and the stirring time is 50-60min in the crosslinking process.
8. The method for preparing the hemostatic and antibacterial medical material according to claim 7, wherein the method comprises the steps of: in the step S2, in the ultrasonic dispersion process, the ultrasonic power is 500-600W, and the ultrasonic time is 20-30min.
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| CN110694101A (en) * | 2019-11-25 | 2020-01-17 | 高敏楠 | Medical wound tissue hemostasis and repair cell glue and adhesive tape combination and method |
| CN112294877A (en) * | 2019-12-10 | 2021-02-02 | 乐清市辰卓电气有限公司 | Medical gel with antibacterial and anti-inflammatory effects |
| WO2023157150A1 (en) * | 2022-02-16 | 2023-08-24 | 持田製薬株式会社 | Use of polysaccharide derivative |
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2024
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| CN1552215A (en) * | 2003-06-06 | 2004-12-08 | 上海高科联合生物技术研发有限公司 | Sterilizing gel, preparing method and application thereof |
| CN106730017A (en) * | 2016-12-14 | 2017-05-31 | 广东省微生物研究所（广东省微生物分析检测中心） | A kind of sustained-release antibacterial composite membrane of bootable bone tissue regeneration and preparation method thereof |
| CN108686257A (en) * | 2018-06-21 | 2018-10-23 | 浙江派菲特新材料科技有限公司 | A kind of high anti-microbial property adhesive of medical |
| CN109568643A (en) * | 2018-10-21 | 2019-04-05 | 浙江理工大学 | A kind of preparation method and applications of the antibacterial anti hemorrhagic microballoon containing jamaicin |
| CN110052228A (en) * | 2019-04-25 | 2019-07-26 | 泉州师范学院 | It is a kind of with light stress hydrophobe transition response function cellulose aerogels microballoon and preparation method thereof |
| CN110665053A (en) * | 2019-10-31 | 2020-01-10 | 河南亚都实业有限公司 | Medical composite collagen sponge dressing |
| CN110694101A (en) * | 2019-11-25 | 2020-01-17 | 高敏楠 | Medical wound tissue hemostasis and repair cell glue and adhesive tape combination and method |
| CN112294877A (en) * | 2019-12-10 | 2021-02-02 | 乐清市辰卓电气有限公司 | Medical gel with antibacterial and anti-inflammatory effects |
| WO2023157150A1 (en) * | 2022-02-16 | 2023-08-24 | 持田製薬株式会社 | Use of polysaccharide derivative |
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