CN111617308A - Antibacterial medical hemostatic sponge and preparation method thereof - Google Patents
Antibacterial medical hemostatic sponge and preparation method thereof Download PDFInfo
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- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L24/0015—Medicaments; Biocides
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0036—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
- A61L24/0089—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing inorganic fillers not covered by groups A61L24/0078 or A61L24/0084
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
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- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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- C08J2201/00—Foams characterised by the foaming process
- C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
- C08J2201/048—Elimination of a frozen liquid phase
- C08J2201/0482—Elimination of a frozen liquid phase the liquid phase being organic
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- C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
- C08J2201/048—Elimination of a frozen liquid phase
- C08J2201/0484—Elimination of a frozen liquid phase the liquid phase being aqueous
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- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/04—Alginic acid; Derivatives thereof
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- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
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- C08J2389/00—Characterised by the use of proteins; Derivatives thereof
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- C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
- C08J2405/04—Alginic acid; Derivatives thereof
Abstract
The invention provides an antibacterial medical hemostatic sponge, which is prepared from biomacromolecules, halloysite and an antibacterial agent; the biomacromolecule is used as a porous sponge framework, and the halloysite is loaded with an antibacterial agent. The application also provides a preparation method of the antibacterial medical hemostatic sponge. The long-acting antibacterial hemostatic material provided by the invention can realize high-efficiency hemostasis, has an effective hemostatic effect on a liver hemorrhage model, and has good long-term antibacterial property; in addition, the preparation method is simple and easy to implement, has no pollution to the environment, and is easy to realize large-scale production.
Description
Technical Field
The invention relates to the technical field of biomedical high polymer materials and long-acting antibiosis, in particular to an antibacterial medical hemostatic sponge and a preparation method thereof.
Background
Excessive blood loss is a major cause of casualties in hospital, emergency and battlefield environments. For example, uncontrolled bleeding on a battlefield can result in mortality rates of about 50%, while major bleeding in surgery and first aid is a common problem for physicians. Therefore, research on hemostatic materials is receiving attention. Typically, hemostasis is achieved through a series of coagulation cascades, including the formation of a thrombus by activated platelets, which in turn activate various coagulation factors via intrinsic and/or extrinsic enzymatic pathways, thereby further enhancing the thrombus strength of the platelets. Currently, the hemostatic materials available in the market mainly focus on absorbing the liquid in blood, increasing the concentration of blood cells near the wound, activating platelets, promoting hemostasis, and promoting hemostasis by adding substances that promote the coagulation cascade, such as kaolin and the like.
The ideal hemostatic material needs to have the advantages of safety, high efficiency, easy storage, low cost, good biocompatibility and the like. In the prior art, various excellent hemostatic materials are provided, and as reported in patent application No. 201811414167.7, a preparation method of physically cross-linked natural polysaccharide microspheres is disclosed, which uses one or more polysaccharides of hydroxyethyl cellulose, chitosan, starch, sodium alginate and hyaluronic acid to obtain microspheres with hemostatic effect by a physical cross-linking method. The patent with application number 201820674045.0 reports a gelatin hemostatic sponge, which is made of a sponge substrate and a reticular layer which is wrapped on the surface of the sponge substrate and is in a reticular structure formed by crosslinking gelatin molecules, and the hemostatic sponge generates a hemostatic effect by contacting and pressing a wound bleeding part, and part of jelly plays a role in sealing bleeding points to stop bleeding while absorbing liquid. However, these inventions neglect a critical problem, and wound infection during hemostasis can cause many sequelae, such as amputation, prolonged healing time of abscess-shaped wound, etc. Therefore, antibacterial hemostatic materials have become the focus of current research.
Disclosure of Invention
The invention aims to provide an antibacterial medical hemostatic sponge and a preparation method thereof, and the antibacterial medical hemostatic sponge provided by the application has excellent hemostatic performance, broad-spectrum antibacterial property and better antibacterial durability.
In view of the above, the application provides an antibacterial medical hemostatic sponge, which is prepared from biomacromolecules, halloysite and an antibacterial agent; the biomacromolecule is used as a sponge framework, and the halloysite is loaded with an antibacterial agent.
Preferably, the antibacterial agent is selected from one or more of ciprofloxacin hydrochloride, gentamicin and ofloxacin, and the biomacromolecule is selected from one or more of sodium alginate, gelatin, chitosan, dextran and hyaluronic acid.
Preferably, the mass ratio of the antibacterial agent to the halloysite is 1: (0.1-2), wherein the ratio of the total mass of the halloysite and the antibacterial agent to the mass of the biomacromolecule is 1: (1-8).
The application also provides a preparation method of the antibacterial medical hemostatic sponge, which comprises the following steps:
A) dissolving the antibacterial agent, mixing with halloysite, and vacuumizing the obtained mixed solution to obtain the halloysite loaded with the antibacterial agent;
B) dissolving biological macromolecules in water, mixing with the antibacterial agent-loaded halloysite, and freeze-drying to obtain the antibacterial medical hemostatic sponge.
Preferably, the solvent in which the antibacterial agent is dissolved is water, ethanol or acetic acid.
Preferably, the mass percentage concentration of the solution formed by dissolving the biological macromolecules in water is 0.4-2%.
Preferably, the vacuumizing is performed in a circulating vacuumizing mode, the time of each vacuumizing of the circulating vacuumizing is 30-40 min, and the circulating is performed for 3-4 times.
Preferably, the freeze drying time is 24-30 h.
Preferably, if the biomacromolecule is sodium alginate or a biomacromolecule containing sodium alginate, the method further comprises the following step B):
the antibacterial medical hemostatic sponge is soaked in a calcium chloride solution, wherein the mass percentage of calcium chloride in the calcium chloride solution is 2-5%, and the soaking time is 2-4 hours.
The application provides medical hemostasis sponge of antibiotic type, it is obtained by biological macromolecule, halloysite and antibacterial agent preparation, biological macromolecule is as porous sponge skeleton, just the halloysite load has the antibacterial agent. The porous structure of the antibacterial medical hemostatic sponge and the halloysite are sources for efficient hemostasis of the sponge, and the adopted hollow tubular halloysite can be combined with an antibacterial agent through capillarity, electrostatic interaction and hydrogen bonds to serve as an antibacterial source of the sponge, so that the sponge has good antibacterial durability while efficiently stopping bleeding, and further, the infection of bacteria outside and in other places to wounds in hemostasis is avoided; furthermore, the hollow tube structure of the halloysite can load the antibacterial agent inside through capillary phenomenon to achieve the effect of slowly releasing the drug, so that the halloysite loaded with the antibacterial agent is a source for providing broad-spectrum antibacterial and long-acting antibacterial.
Drawings
FIG. 1 is a low magnification SEM photograph of the antibacterial medical hemostatic sponge prepared in example 1;
fig. 2 is a high-magnification SEM photograph of the antibacterial medical hemostatic sponge prepared in example 1.
Detailed Description
For a further understanding of the invention, reference will now be made to the preferred embodiments of the invention by way of example, and it is to be understood that the description is intended to further illustrate features and advantages of the invention, and not to limit the scope of the claims.
In view of the problem that the existing hemostatic material has poor antibacterial property, the application provides an antibacterial medical hemostatic sponge which has antibacterial and hemostatic properties and good antibacterial durability. Specifically, the embodiment of the invention discloses an antibacterial medical hemostatic sponge which is prepared from biomacromolecules, halloysite and an antibacterial agent; the biological macromolecules serve as a porous sponge framework; the halloysite is loaded with an antimicrobial agent.
The application the antibiotic hemostatic sponge is a porous spongy material of biomacromolecule-medicine-carrying halloysite, which takes biomacromolecule and medicine-carrying halloysite as main components, wherein the medicine-carrying halloysite is that the halloysite is loaded with the antibacterial agent.
For the raw material, the antibacterial agent is selected from one or more of ciprofloxacin hydrochloride, gentamicin and ofloxacin. The biomacromolecule is selected from one or more of sodium alginate, gelatin, chitosan, dextran and hyaluronic acid; compared with other macromolecular materials, the biomacromolecule has good degradability and biocompatibility. The mass ratio of the antibacterial agent to the halloysite is 1: (0.1-2), wherein the ratio of the total mass of the halloysite and the antibacterial agent to the mass of the biomacromolecule is 1: (1-8).
The application also provides a preparation method of the antibacterial medical hemostatic sponge, which comprises the following steps:
A) dissolving the antibacterial agent, mixing with halloysite, and vacuumizing the obtained mixed solution to obtain the halloysite loaded with the antibacterial agent;
B) dissolving biological macromolecules in water, mixing with the antibacterial agent-loaded halloysite, and freeze-drying to obtain the antibacterial medical hemostatic sponge.
In the process of preparing the antibacterial medical hemostatic sponge, the antibacterial agent is dissolved to be in a saturated state, then the antibacterial agent is mixed with the halloysite, and the obtained mixed solution is vacuumized to obtain the halloysite loaded with the antibacterial agent; the antibacterial agent is in a saturated state and is vacuumized together with the halloysite to ensure that the hollow tube structure of the halloysite can load the antibacterial agent through capillary phenomenon, so that the slow release of the antibacterial agent in the sponge is realized. The solvent in which the antibacterial agent is dissolved is water, ethanol or acetic acid, and halloysite has better dispersibility in the solvent than other solvents. This application adopts hollow tubulose halloysite can combine with the antibacterial agent through capillarity, electrostatic interaction and hydrogen bond effect, and regard as the antibiotic source of sponge, and the slow release nature of antibacterial agent makes the sponge have better antibiotic persistence in high-efficient hemostasis, and then has avoided the infection of outside and other local bacterium to the wound in hemostasis. In order to have larger load capacity of the halloysite, the halloysite can be stored for a long time at room temperature by vacuumizing in a circulating way and performing centrifugal cleaning after vacuum circulation to obtain the halloysite carrying the antibacterial agent; in the circulation vacuum pumping mode, the time for each time of vacuum pumping is 30-40 min, and the circulation is performed for 3-4 times.
According to the invention, the biological macromolecules are dissolved in water and then mixed with the antimicrobial-loaded halloysite, and the mixture is frozen and dried to obtain the antimicrobial medical hemostatic sponge. In the process, the mass percentage concentration of the water solution formed by dissolving the biomacromolecules in water is 0.4-2%, and more preferably 2%. The biomacromolecule is used as a porous sponge framework, the concentration of the biomacromolecule has certain influence on the appearance and the mechanical property of the sponge, and when the mass percentage concentration of the biomacromolecule water solution is 0.4-2%, the sponge has a better appearance structure. The freeze-drying is a technical means well known to those skilled in the art, and the specific embodiments thereof are not particularly limited in the present application; the freeze drying time is 24-30 h.
In order to better stabilize the medical antibacterial hemostatic sponge with the sodium alginate biomacromolecules as the framework, after the medical antibacterial hemostatic sponge is obtained, the sodium alginate sponge framework is subjected to coordination crosslinking by using calcium ions, so that the stability of the sponge framework is improved; the method specifically comprises the following steps: soaking the sodium alginate antibacterial medical hemostatic sponge in a calcium chloride solution, wherein the mass percentage of calcium chloride in the calcium chloride solution is 2-5%, and the soaking time is 2-4 h.
The biological macromolecule and the halloysite loaded with the antibacterial agent are used as main raw materials, and the porous sponge material with high-efficiency hemostasis and long-acting antibiosis can be obtained by simply mixing, stirring and freeze drying. The long-acting antibacterial hemostatic material provided by the invention can realize high-efficiency hemostasis, can effectively finish in-vitro hemostasis within 20s, has an effective hemostatic effect on a liver hemorrhage model, has good long-term antibacterial property, and is simple and easy to prepare, free of environmental pollution and easy to realize large-scale production.
For further understanding of the present invention, the following examples are provided to illustrate the antibacterial medical hemostatic sponge and the preparation method thereof, and the scope of the present invention is not limited by the following examples.
Example 1
The preparation method of the high-efficiency hemostasis and long-acting antibacterial hemostasis porous sponge comprises the following steps:
dissolving ciprofloxacin hydrochloride in ultrapure water to prepare a saturated solution; adding ground halloysite with the mass ratio of 1:2 to ciprofloxacin hydrochloride, stirring for 1 hour, and performing ultrasonic treatment at room temperature for 15 minutes to improve the dispersibility of the halloysite in the aqueous solution; vacuumizing by using a circulating vacuum method, wherein the vacuum time is 30 minutes each time, and circulating for 3 times; centrifuging at 10000rpm for 10 minutes, cleaning with ultrapure water for 3 times, and drying at 60 ℃ for 5 hours to obtain halloysite loaded with ciprofloxacin hydrochloride;
dissolving sodium alginate in ultrapure water, preparing a sodium alginate solution with the mass percent of 2%, adding drug-loaded halloysite with the mass ratio of 1:2 to the sodium alginate solution, and stirring for 4 hours to uniformly mix the drug-loaded halloysite in the sodium alginate; pouring the mixed mixture of sodium alginate and drug-loaded halloysite into a template, and freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure;
soaking sponge material with porous structure in 2 wt% of CaCl2And in 4 hours, calcium ions in the calcium chloride can perform coordination reaction with carboxyl in the sodium alginate to obtain the hemostatic and antibacterial sponge with stable internal crosslinking. SEM photographs of the hemostatic and antibacterial sponge prepared according to the present application are specifically shown in fig. 1 and 2.
Example 2
The preparation method of the high-efficiency hemostasis and long-acting antibacterial hemostasis porous sponge comprises the following steps:
dissolving gentamicin in ultrapure water to prepare a saturated solution; adding the ground halloysite with the mass ratio of 1:2 to gentamicin, stirring for 1 hour, and performing ultrasonic treatment at room temperature for 15 minutes to improve the dispersibility of the halloysite in the aqueous solution; vacuumizing by using a circulating vacuum method, wherein the vacuum time is 30 minutes each time, and circulating for 3 times; centrifuging at 10000rpm for 10 minutes, cleaning with ultrapure water for 3 times, and drying at 60 ℃ for 5 hours to obtain the gentamicin-loaded halloysite;
dissolving sodium alginate and glucan in ultrapure water, preparing a sodium alginate and glucan solution with the mass percent of 2%, adding drug-loaded halloysite with the mass ratio of 1:2 to the sodium alginate and the glucan into the sodium alginate solution, and stirring for 4 hours to uniformly mix the drug-loaded halloysite in the sodium alginate; pouring the mixed mixture of sodium alginate and drug-loaded halloysite into a template, and freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure;
soaking sponge material with porous structure in 2 wt% of CaCl2And in 4 hours, calcium ions in the calcium chloride can perform coordination reaction with carboxyl in the sodium alginate to obtain the hemostatic and antibacterial sponge with stable internal crosslinking.
Example 3
The preparation method of the high-efficiency hemostasis and long-acting antibacterial hemostasis porous sponge comprises the following steps:
dissolving ciprofloxacin hydrochloride in water to prepare a saturated solution; adding ground halloysite with the mass ratio of 1:2 to ciprofloxacin hydrochloride, stirring for 1 hour, and performing ultrasonic treatment at room temperature for 15 minutes to improve the dispersibility of the halloysite in the aqueous solution; vacuumizing by using a circulating vacuum method, wherein the vacuum time is 30 minutes each time, and circulating for 3 times; centrifuging at 10000rpm for 10 minutes, cleaning with ultrapure water for 3 times, and drying at 60 ℃ for 5 hours to obtain halloysite loaded with ciprofloxacin hydrochloride;
dissolving sodium alginate and gelatin in ultrapure water, preparing a sodium alginate and gelatin solution with the mass percent of 2%, adding the drug-loaded halloysite with the mass ratio of 1:2 to the sodium alginate and the gelatin, stirring for 4 hours, and uniformly mixing the drug-loaded halloysite in the biomacromolecule solution; pouring the mixed mixture into a template, and freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure;
soaking sponge material with porous structure in 2 wt% of CaCl2And in 4 hours, calcium ions in the calcium chloride can perform coordination reaction with carboxyl in the sodium alginate to obtain the hemostatic and antibacterial sponge with stable internal crosslinking.
Example 4
The preparation method of the high-efficiency hemostasis and long-acting antibacterial hemostasis porous sponge comprises the following steps:
dissolving ciprofloxacin hydrochloride in water to prepare a saturated solution; adding ground halloysite with the mass ratio of 1:2 to ciprofloxacin hydrochloride, stirring for 1 hour, and performing ultrasonic treatment at room temperature for 15 minutes to improve the dispersibility of the halloysite in the aqueous solution; vacuumizing by using a circulating vacuum method, wherein the vacuum time is 30 minutes each time, and circulating for 3 times; centrifuging at 10000rpm for 10 minutes, cleaning with ultrapure water for 3 times, and drying at 60 ℃ for 5 hours to obtain halloysite loaded with ciprofloxacin hydrochloride;
dissolving chitosan in acetic acid to prepare a chitosan solution with the mass percent of 2%, adding the drug-loaded halloysite with the mass ratio of 1:2 into the chitosan solution, and stirring for 4 hours to uniformly mix the drug-loaded halloysite in the biomacromolecule solution; and pouring the mixed mixture into a template, and freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure, thereby obtaining the hemostatic and antibacterial sponge.
Experimental example 5 use of highly effective hemostatic, long-term antibacterial porous hemostatic sponge, the following experiment proves
1) Time of hemostasis in vitro
Detection of in vitro clotting time for the highly effective hemostatic, long-lasting antimicrobial porous hemostatic sponges obtained in examples 1-4
The whole blood used in the experiment is rabbit whole blood which contains 10% sodium citrate anticoagulant by mass; placing 10 mg of sponge and 1 ml of blood in a centrifuge tube, incubating for 5 minutes at 37 ℃, adding 100 microliters of 0.025mol/L calcium chloride solution, immediately starting timing, inverting the centrifuge tube, stopping timing when the blood does not flow down any more, and recording the blood coagulation time; the results are shown in tables 1 to 4;
TABLE 1 statistical data sheet for in vitro clotting time of the antibacterial hemostatic sponge prepared in example 1
| Numbering | Negative control group | Commercial gelatin | Control group | Example 1 |
| Hemostasis time(s) | 600±20 | 200±10 | 60±5 | 17±2 |
Note: the negative control group is blood with 100 microliter of 0.025mol/L calcium chloride;
the control group was a sodium alginate sponge without drug loaded halloysite: dissolving sodium alginate in ultrapure water, preparing a sodium alginate solution with the mass percent of 2%, pouring the sodium alginate solution into a template, freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure, and soaking the spongy substance with the porous structure in CaCl with the mass percent of 2%2Neutralizing for 4 hours to obtain the hemostatic sponge with stable internal crosslinking;
the commercial gelatin is a domestic kuaikang (gelatin hemostatic sponge) (trade name:
hemostatic sponges, Jiangxi Zhongqiang industry Co., Ltd.).
Through detection, the porous hemostatic sponge with high-efficiency hemostasis and long-acting antibiosis can effectively finish hemostasis within 20 s.
TABLE 2 statistical data sheet for in vitro clotting time of the antibacterial hemostatic sponge prepared in example 2
| Numbering | Negative control group | Commercial gelatin | Control group | Example 2 |
| Hemostasis time(s) | 600±20 | 200±10 | 105±5 | 19±5 |
Note: the negative control group is blood with 100 microliter of 0.025mol/L calcium chloride;
the control group was sodium alginate and dextran sponge without drug loaded halloysite: dissolving sodium alginate and glucan in ultrapure water, preparing a sodium alginate and glucan solution with the mass percent of 2%, pouring the solution into a mouldFreeze-drying the plate for 24-30 hours to obtain a spongy substance with a porous structure; soaking sponge material with porous structure in 2 wt% of CaCl2In 4 hours, calcium ions in the calcium chloride can perform coordination reaction with carboxyl in the sodium alginate to obtain the hemostatic sponge with stable internal crosslinking;
the commercial gelatin is a domestic kuaikang (gelatin hemostatic sponge) (trade name:
hemostatic sponges, Jiangxi Zhongqiang industry Co., Ltd.).
Through detection, the porous hemostatic sponge with high-efficiency hemostasis and long-acting antibiosis can effectively finish hemostasis within 20 s.
Table 3 statistical data table of in vitro clotting time of the antibacterial hemostatic sponge prepared in example 3
| Numbering | Negative control group | Commercial gelatin | Control group | Example 3 |
| Hemostasis time(s) | 600±20 | 200±10 | 180±5 | 20±3 |
Note: the negative control group was blood supplemented with 100. mu.l of 0.025mol/L calcium chloride;
the control group was sodium alginate and gelatin sponge without drug loaded halloysite: dissolving sodium alginate and gelatin in ultrapure water, preparing a sodium alginate and gelatin solution with the mass percent of 2%, pouring the solution into a template, and freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure; soaking sponge material with porous structure in 2 wt% of CaCl2In 4 hours, calcium ions in the calcium chloride can perform coordination reaction with carboxyl in the sodium alginate to obtain the hemostatic sponge with stable internal crosslinking;
the commercial gelatin is a domestic kuaikang (gelatin hemostatic sponge) (trade name:
hemostatic sponges, Jiangxi Zhongqiang industry Co., Ltd.).
Through detection, the porous hemostatic sponge with high-efficiency hemostasis and long-acting antibiosis can effectively finish hemostasis within 20 s.
Table 4 statistical data table of in vitro clotting times for the antibacterial hemostatic sponges prepared in example 4
| Numbering | Negative control group | Commercial gelatin | Control group | Example 4 |
| Hemostasis time(s) | 600±20 | 200±10 | 110±5 | 21±4 |
Note: the negative control group is blood with 100 microliter of 0.025mol/L calcium chloride;
the control group was chitosan sponge without drug loaded halloysite: dissolving chitosan in acetic acid to prepare a chitosan solution with the mass percent of 2%, pouring the solution into a template, and freeze-drying for 24-30 hours to obtain the hemostatic sponge;
the commercial gelatin is a domestic kuaikang (gelatin hemostatic sponge) (trade name:
hemostatic sponges, Jiangxi Zhongqiang industry Co., Ltd.).
Through detection, the porous hemostatic sponge with high-efficiency hemostasis and long-acting antibiosis can effectively finish hemostasis within 20 s.
Experimental example 6
The liver injury bleeding of SD rats was used as a model:
the in vivo hemostasis function detection is carried out on the high-efficiency hemostasis and long-acting antibacterial porous hemostasis sponge obtained in the embodiment 1-4, and the specific detection method comprises the following steps:
taking the liver injury of an SD rat as a model, carrying out intraperitoneal injection anesthesia by using chloral hydrate solution, and making a 1cm wound on the left liver lobe by using a scalpel; placing a sponge with the volume of 1cm multiplied by 0.5cm at the wound part, slightly pressing, observing the hemostasis condition, and recording the bleeding time, wherein the results are shown in tables 5-8;
TABLE 5 data table of hemostatic time of rat liver for antibacterial hemostatic sponge prepared in example 1
| Numbering | Negative control group | Commercial gelatin | Control group | Example 1 |
| Hemostasis time(s) | 360±20 | 170±10 | 106±5 | 38±2 |
Note: the negative control group is an untreated SD rat liver model;
the control group was a sodium alginate sponge without drug loaded halloysite: dissolving sodium alginate in ultrapure water, preparing a sodium alginate solution with the mass percent of 2%, pouring the solution into a template, freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure, and soaking the spongy substance with the porous structure in CaCl with the mass percent of 2%2In 4 hours, calcium ions in the calcium chloride can perform coordination reaction with carboxyl in the sodium alginate to obtain the hemostatic sponge with stable internal crosslinking;
the commercial gelatin is a domestic kuaikang (gelatin hemostatic sponge) (trade name:
hemostatic sponges, Jiangxi Zhongqiang industry Co., Ltd.).
The test results in table 5 show that the highly effective hemostatic, long-acting antibacterial porous hemostatic sponge provided by the invention can stop the liver bleeding of the SD rat within 40s, and has highly effective hemostatic performance. Hemostasis can be effectively completed within 40 s.
Table 6 table of hemostatic time of rat liver for antibacterial hemostatic sponge prepared in example 2
| Numbering | Negative control group | Commercial gelatin | Control group | Example 2 |
| Hemostasis time(s) | 360±20 | 170±10 | 120±5 | 37±5 |
Note: the negative control group is an untreated SD rat liver model;
the control group was sodium alginate and dextran sponge without drug loaded halloysite: dissolving sodium alginate and glucan in ultrapure water, preparing a sodium alginate and glucan solution with the mass percent of 2%, pouring the solution into a template, and freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure; soaking sponge material with porous structure in 2 wt% of CaCl2In 4 hours, calcium ions in the calcium chloride can perform coordination reaction with carboxyl in the sodium alginate to obtain the hemostatic sponge with stable internal crosslinking;
the commercial gelatin is a domestic kuaikang (gelatin hemostatic sponge) (trade name:
hemostatic sponges, Jiangxi Zhongqiang industry Co., Ltd.).
The test results in table 6 show that the highly effective hemostatic, long-acting antibacterial porous hemostatic sponge provided by the invention can stop the liver bleeding of the SD rat within 40s, and has highly effective hemostatic performance.
Table 7 table of hemostatic time of rat liver for antibacterial hemostatic sponge prepared in example 3
| Numbering | Negative control group | Commercial gelatin | Control group | Example 3 |
| Hemostasis time(s) | 360±20 | 170±10 | 115±5 | 39±3 |
Note: the negative control group is an untreated SD rat liver model;
the control group was sodium alginate and gelatin sponge without drug loaded halloysite: dissolving sodium alginate and gelatin in ultrapure water, preparing a sodium alginate and gelatin solution with the mass percent of 2%, pouring the solution into a template, and freeze-drying for 24-30 hours to obtain the spongy substance with the porous structure. Will have a porous structureSoaking cotton-like substance in 2% CaCl2In 4 hours, calcium ions in the calcium chloride can perform coordination reaction with carboxyl in the sodium alginate to obtain the hemostatic sponge with stable internal crosslinking;
the commercial gelatin is a domestic kuaikang (gelatin hemostatic sponge) (trade name:
hemostatic sponges, Jiangxi Zhongqiang industry Co., Ltd.).
The test results in table 7 show that the highly effective hemostatic, long-acting antibacterial porous hemostatic sponge provided by the invention can stop liver bleeding of SD rats within 40s, and has highly effective hemostatic performance.
Table 8 table of hemostatic time of rat liver for antibacterial hemostatic sponge prepared in example 4
| Numbering | Negative control group | Commercial gelatin | Control group | Example 4 |
| Hemostasis time(s) | 360±20 | 170±10 | 95±5 | 41±4 |
Note: the negative control group is an untreated SD rat liver model;
the control group was chitosan sponge without drug loaded halloysite: dissolving chitosan in acetic acid to prepare a chitosan solution with the mass percent of 2%, pouring the solution into a template, and freeze-drying for 24-30 hours to obtain a spongy substance with a porous structure, thereby obtaining the hemostatic sponge;
the commercial gelatin is a domestic kuaikang (gelatin hemostatic sponge) (trade name:
hemostatic sponges, Jiangxi Zhongqiang industry Co., Ltd.).
The test results in table 8 show that the highly effective hemostatic, long-acting antibacterial porous hemostatic sponge provided by the invention can stop the liver bleeding of SD rats within 40s, and has highly effective hemostatic performance.
Experimental example 7
The porous hemostatic sponge with high-efficiency hemostasis and long-acting antibiosis obtained in the embodiment 1-4 is subjected to an antibiosis experiment, and the specific detection method comprises the following steps:
the highly effective hemostatic, long-acting antibacterial porous hemostatic sponges of examples 1-4 were made into 1cm × 1cm × 3mm sheets, and the antibacterial property of the obtained sponges was tested according to standard astm e2149-01, and the bacteria used for detection were escherichia coli and staphylococcus aureus, and the detection results were as follows:
TABLE 9 antibacterial statistical data Table for antibacterial hemostatic sponges prepared in examples 1-4
| Fungus | Example 1 | Example 2 | Example 3 | Example 4 |
| Escherichia coli | 98.8％ | 97.6％ | 98.6％ | 97.4％ |
| Staphylococcus aureus | 99.7％ | 98.6％ | 98.2％ | 98.4％ |
The test results in table 9 show that the antibacterial property of the porous hemostatic sponge with high-efficiency hemostasis and long-acting antibacterial property provided by the invention is more than 95%, and the porous hemostatic sponge shows excellent antibacterial property.
After the antibacterial sponges are soaked in water at 37 ℃ for one week, the antibacterial property of each sponge is tested according to standard ASTM E2149-01, and the test results are as follows:
TABLE 10 results of the test of antibacterial longevity of the antibacterial hemostatic sponges prepared in examples 1-4
| Fungus | Example 1 | Example 2 | Example 3 | Example 4 |
| Escherichia coli | 95.7％ | 93.4％ | 95.8％ | 95.3％ |
| Staphylococcus aureus | 96.2％ | 96.5％ | 95.9％ | 96.5％ |
The test results in table 10 show that the antibacterial property of the porous hemostatic sponge with high-efficiency hemostasis and long-acting antibacterial properties provided by the invention can still reach more than 93% after being soaked for one week, and thus, the hemostatic antibacterial sponge provided by the invention has excellent antibacterial durability.
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (9)
1. An antibacterial medical hemostatic sponge is prepared from biological macromolecule, halloysite and antibacterial agent; the biomacromolecule is used as a sponge framework, and the halloysite is loaded with an antibacterial agent.
2. The antibacterial medical hemostatic sponge according to claim 1, wherein the antibacterial agent is one or more selected from ciprofloxacin hydrochloride, gentamicin and ofloxacin, and the biomacromolecule is one or more selected from sodium alginate, gelatin, chitosan, dextran and hyaluronic acid.
3. The antibacterial medical hemostatic sponge according to claim 1, wherein the mass ratio of the antibacterial agent to the halloysite is 1: (0.1-2), wherein the ratio of the total mass of the halloysite and the antibacterial agent to the mass of the biomacromolecule is 1: (1-8).
4. A method for preparing an antibacterial medical hemostatic sponge according to any one of claims 1 to 3, comprising the steps of:
A) dissolving the antibacterial agent, mixing with halloysite, and vacuumizing the obtained mixed solution to obtain the halloysite loaded with the antibacterial agent;
B) dissolving biological macromolecules in water, mixing with the antibacterial agent-loaded halloysite, and freeze-drying to obtain the antibacterial medical hemostatic sponge.
5. The method according to claim 4, wherein the solvent in which the antibacterial agent is dissolved is water, ethanol or acetic acid.
6. The preparation method according to claim 4, wherein the mass percentage concentration of the solution formed by dissolving the biomacromolecule in water is 0.4-2%.
7. The preparation method according to claim 4, wherein the evacuation is performed in a cyclic evacuation manner, and each evacuation time of the cyclic evacuation is 30-40 min and is performed for 3-4 times.
8. The preparation method according to claim 4, wherein the freeze-drying time is 24-30 hours.
9. The method according to claim 4, wherein the biomacromolecule, if sodium alginate or a biomacromolecule containing sodium alginate, further comprises the following steps after step B):
the antibacterial medical hemostatic sponge is soaked in a calcium chloride solution, wherein the mass percentage of calcium chloride in the calcium chloride solution is 2-5%, and the soaking time is 2-4 hours.
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| CN112516375A (en) * | 2020-12-07 | 2021-03-19 | 中国科学院长春应用化学研究所 | Self-adaptive degradable hemostatic material and preparation method thereof |
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|---|---|---|---|---|
| CN102527329A (en) * | 2011-12-31 | 2012-07-04 | 郑州大学 | Alginate/halloysite nanotube composite-porous ball and preparation method therefor |
| CN103316376A (en) * | 2013-05-27 | 2013-09-25 | 暨南大学 | Endellite composite chitosan haemostasis and wound restoration sponge material, preparation and applications |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102527329A (en) * | 2011-12-31 | 2012-07-04 | 郑州大学 | Alginate/halloysite nanotube composite-porous ball and preparation method therefor |
| CN103316376A (en) * | 2013-05-27 | 2013-09-25 | 暨南大学 | Endellite composite chitosan haemostasis and wound restoration sponge material, preparation and applications |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112516375A (en) * | 2020-12-07 | 2021-03-19 | 中国科学院长春应用化学研究所 | Self-adaptive degradable hemostatic material and preparation method thereof |
| CN112516375B (en) * | 2020-12-07 | 2021-09-21 | 中国科学院长春应用化学研究所 | Self-adaptive degradable hemostatic material and preparation method thereof |
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