CN112295013B - Anti-inflammation type rapid hemostasis medical adhesive material and preparation method thereof - Google Patents

Anti-inflammation type rapid hemostasis medical adhesive material and preparation method thereof Download PDF

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CN112295013B
CN112295013B CN202011197512.3A CN202011197512A CN112295013B CN 112295013 B CN112295013 B CN 112295013B CN 202011197512 A CN202011197512 A CN 202011197512A CN 112295013 B CN112295013 B CN 112295013B
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medical adhesive
inflammatory
carboxymethyl chitosan
adhesive material
ionic liquid
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CN112295013A (en
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王威
田霞
张俊杰
张怡婷
田素
郭修峰
田野
费维滢
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Beijing Fal Technology Development Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/08Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/0005Ingredients of undetermined constitution or reaction products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001Use of materials characterised by their function or physical properties
    • A61L24/0015Medicaments; Biocides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/232Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/30Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/41Anti-inflammatory agents, e.g. NSAIDs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/418Agents promoting blood coagulation, blood-clotting agents, embolising agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/04Materials for stopping bleeding

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Abstract

The invention belongs to the technical field of biomedical materials, and particularly relates to an anti-inflammatory rapid hemostatic medical adhesive material and a preparation method thereof. The medical adhesive material takes alpha-n-butyl cyanoacrylate and alpha-n-octyl cyanoacrylate as mixed medical adhesive matrix and uses CO2The supercritical fluid carries the selected ionic liquid and the anti-inflammatory active ingredients to carry out swelling modification on the hemostatic material carboxymethyl chitosan, so that the hemostatic performance of the carboxymethyl chitosan is effectively improved, the hemostatic performance of the whole medical adhesive material is greatly improved, rapid hemostasis is realized, the medical adhesive has good antibacterial performance, and the medical adhesive is suitable for more clinical occasions.

Description

Anti-inflammation type rapid hemostatic medical adhesive material and preparation method thereof
Technical Field
The invention belongs to the technical field of biomedical materials, and particularly relates to an anti-inflammatory rapid hemostatic medical adhesive material and a preparation method thereof.
Background
The medical adhesive is a preparation, a material or a substance which can be adhered to the surface or can cause the surface to be adhered in the aspect of medical treatment, belongs to biomedical special functional adhesive, is mainly used for local adhesion and repair of organs or tissues, replaces the technical fields of traditional suturing, or combination and positioning of tissues and blood vessels for plugging and the like, and has the biomedical function besides the common adhesive bonding function and the mechanical function. Compared with the traditional methods such as suturing and nailing, the use of the medical adhesive can effectively shorten the operation time and obviously reduce the pain of patients, and is the preferred material for the current medical operation.
Currently, cyanoacrylate medical adhesives have been rapidly developed and widely used clinically in recent decades. Structure CNCH of cyanoacrylate medical glue2In CCOOR, alpha-carbon atom is combined with-CN, -COOR group, so that the carbon atom at beta position generates stronger electroabsorbability, and only a very trace amount of anions (-OH, -NH) are met2) I.e., instantaneously polymerize. Because the basic substance of the organism tissue is protein, the protein is a linear macromolecular compound consisting of amino acid, and the two ends of the macromolecule contain-NH2and-COOH group, the cyanoacrylate medical adhesive has the fastest polymerization speed on organism tissues and obvious performance advantage.
In addition, when the cyanoacrylate medical adhesive is used on biological tissues, due to the existence of trace alkalescent materials such as tissue fluid, water or blood and the like on the biological tissues, the cyanoacrylate monomer can be rapidly initiated to generate anionic polymerization at room temperature, and then the alpha-cyanoacrylate monomer is solidified into an adhesive film, the adhesive film is scanned under an electron microscope to form a polymer with a 2-3 micron fiber mesh structure, and the adhesive film is tightly embedded with the skin surface, the surgical wound surface, the medical material surface and the like, so that the adhesive can be used for bonding and closing the wound, sealing the small blood vessel mesh of the wound surface fracture to effectively seal and stop bleeding, bonding and fixing autologous tissues and medical materials, and plugging/sealing blood vessels.
However, even though the prior art has developed a cyanoacrylate medical adhesive formed by compounding different cyanoacrylate materials, the adhesive property of the cyanoacrylate medical adhesive is further improved. However, with the increasingly wide application range of medical glue, there is a clinical urgent need for medical glue materials with both hemostatic and adhesive properties to meet the needs of different medical conditions, but the hemostatic properties of pure cyanoacrylate medical glue materials are very limited, and clinical needs cannot be met.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to provide an anti-inflammatory rapid hemostatic medical adhesive material, so as to solve the problem that the pure cyanoacrylate medical adhesive material in the prior art has poor hemostatic performance;
the second technical problem to be solved by the present invention is to provide a preparation method of the anti-inflammatory rapid hemostatic medical adhesive material.
In order to solve the technical problems, the preparation method of the anti-inflammatory rapid hemostatic medical adhesive material comprises the following steps:
(1) uniformly mixing alpha-n-butyl cyanoacrylate and alpha-n-octyl cyanoacrylate to obtain a medical adhesive matrix for later use;
(2) placing carboxymethyl chitosan in a sealed container containing ionic liquid and antiinflammatory active ingredient, removing air, and charging CO into the container2Controlling the temperature and pressure in the closed container to make CO2The gas is in a supercritical state, and under the condition that the carboxymethyl chitosan is not in contact with the ionic liquid and the anti-inflammatory active ingredient, the ionic liquid and the anti-inflammatory active ingredient are carried to carry out modification treatment on the carboxymethyl chitosan, so that the carboxymethyl chitosan to be modified is obtained;
(3) slowly adding the modified carboxymethyl chitosan into the medical gel matrix, fully stirring until the system is in a gel state, and sterilizing to obtain the medical gel matrix.
Specifically, in the step (1), the mass ratio of the n-butyl alpha-cyanoacrylate to the n-octyl alpha-cyanoacrylate is 50-60 wt%: 40-50 wt%.
Specifically, in the step (2), the ionic liquid comprises 1-methylimidazole trifluoroacetate.
Specifically, in the step (2), the addition amount of the ionic liquid accounts for 5-10wt% of the mass of the carboxymethyl chitosan.
Specifically, in the step (2), the anti-inflammatory active ingredient is orostachys fimbriatus juice.
Specifically, in the step (2), the addition amount of the anti-inflammatory active ingredient accounts for 3-8wt% of the mass of the carboxymethyl chitosan.
Specifically, in the step (2), the temperature in the closed container is controlled to be 80-120 ℃ and the pressure is controlled to be 8-10 MP.
Specifically, in the step (2), the time of the modification treatment step is 5-10 min.
Specifically, in the step (3), the mass ratio of the modified carboxymethyl chitosan to the medical gum base is 3-8: 10.
the invention also discloses an anti-inflammatory rapid hemostatic medical adhesive material prepared by the method.
The invention also discloses application of the anti-inflammatory rapid hemostatic medical adhesive material in preparation of a hemostatic material.
The medical adhesive material of the invention takes alpha-n-butyl cyanoacrylate and alpha-n-octyl cyanoacrylate as mixed medical adhesive matrix and CO2The supercritical fluid carries the selected ionic liquid and the anti-inflammatory active ingredients to carry out swelling modification on the hemostatic material carboxymethyl chitosan, so that the hemostatic performance of the carboxymethyl chitosan is effectively improved, the hemostatic performance of the whole medical adhesive material is greatly improved, rapid hemostasis is realized, the medical adhesive has good antibacterial performance, and the medical adhesive is suitable for more clinical occasions.
Detailed Description
Preparation example 1 preparation of n-butyl alpha-cyanoacrylate
The preparation example is used for preparing the required alpha-n-butyl cyanoacrylate and specifically comprises the following steps:
(1) transesterification of butyl esters
CNCH2COOC2H5+C4H9OH—C2H5ONa→CNCH2COOC4H9+C2H5OH
Putting 1400ml of ethyl cyanoacetate and 1200ml of n-butanol into a 5L three-mouth beaker provided with a stirrer and a thermometer, starting stirring, condensing water, heating to 40 ℃ or above, and adding 25g of sodium ethoxide; heating to 100 deg.C, distilling off ethanol when the top temperature reaches 78-82 deg.C, stopping heating when the inner temperature reaches 110 deg.C and the top temperature reaches 98-100 deg.C, and recovering about 680ml ethanol;
cooling to about 50 ℃ of internal temperature, starting a heating and vacuum pump, changing bottles to receive n-butyl cyanoacetate when the vacuum degree is-0.1 MPa and the internal temperature is raised to about 95 ℃ and the top temperature is about 80 ℃, and receiving about 80g of n-butyl cyanoacetate when the bottles are changed; when the internal temperature reaches 130 ℃ and the top temperature reaches 100-;
(2) cracking formaldehyde
【CH2O】n-CH3OH→n CH2O+CH3OH
Putting 3000ml of methanol, 1000g of formaldehyde and 1ml of piperidine into a 5L three-mouth beaker, and cracking solid formaldehyde into monomer formaldehyde, namely methanol formaldehyde solution, under the conditions of micro-heating, reflux and stirring;
(3) synthesis of n-butyl alpha-cyanoacrylate
Figure GDA0002796361130000041
Adding 790ml of methanol formaldehyde solution and 2.1ml of piperidine into a 5L three-neck flask provided with a stirrer, a dropping funnel, a condenser and a water separator, starting to dropwise add 1000ml of n-butyl cyanoacetate when the temperature in the flask reaches 40 ℃ or above, and collecting methanol until the internal temperature reaches 110 ℃; then 400ml of petroleum ether is dripped to begin dehydration and accelerate stirring, about 32ml of water is actually collected after the ether water in the reflux water separator is layered and clarified, and about 400ml of petroleum ether is collected after the water is collected; when the internal temperature reaches 125 ℃, adding 28g of phosphorus pentoxide and 1g of hydroquinone, accelerating the uniform stirring, simultaneously removing the stirrer, the water separator and the dropping funnel, inserting the thermometer and the receiving pipe, connecting the stirrer, the water separator and the dropping funnel with the straight condenser, starting the vacuum pump, removing low-boiling-point substances, continuously adjusting the vacuum degree, changing the receiving bottle when the internal temperature is raised to 140 ℃ after the stirring is stable, and collecting the butyl ester crude monomer when the internal temperature is 160-.
(4) Rectification of n-butyl alpha-cyanoacrylate
A2L two-mouth flask (containing coarse monomer) is provided with an air pipe, a fractionating head, a direct type condenser and a receiving bottle, pressure is reduced, when the vacuum temperature reaches-0.1 MPa or below, the temperature is rapidly increased, when the internal temperature is 95-170 ℃, the rectification monomer is discharged, an air release valve is opened, pressure is increased, a product is taken down and weighed, and then sampling is carried out for chemical analysis.
This preparation was tested to yield the desired n-butyl α -cyanoacrylate.
Preparation example 2 preparation of n-octyl alpha-cyanoacrylate
The preparation example is used for preparing the required n-octyl alpha-cyanoacrylate, and specifically comprises the following steps:
(1) the same as in step (1) of preparation example 1;
(2) the same as in step (2) of preparation example 1;
(3) synthesis of n-octyl alpha-cyanoacrylate
Figure GDA0002796361130000051
380ml of methanol-formaldehyde solution and 0.95ml of piperidine are added into a 5L three-neck flask provided with a stirrer, a dropping funnel, a condenser and a water separator, 750ml of n-octyl cyanoacetate is added dropwise when the temperature in the flask reaches 40 ℃ or above, and methanol is collected until the internal temperature reaches 120 ℃; then 300ml of petroleum ether is dripped to begin dehydration and accelerate stirring, when the ether water in the reflux water separator is layered and clarified, about 16ml of water is actually collected, and about 300ml of petroleum ether is collected after the water is collected; when the internal temperature reaches 130 ℃, adding 20g of phosphorus pentoxide and 2g of hydroquinone, accelerating the uniform stirring, simultaneously removing the stirrer, the water separator and the dropping funnel, inserting the thermometer and the receiving pipe, connecting the stirrer, the water separator and the dropping funnel with the straight condenser, starting the vacuum pump, removing low-boiling-point substances, continuously adjusting the vacuum degree, changing the receiving bottle when the internal temperature is raised to 150 ℃ after the stirring is stable, and collecting octyl ester crude monomers when the internal temperature is 170-;
(4)4.8 rectification of n-octyl alpha-cyanoacrylate
In a 2L two-mouth flask (containing crude monomer), an air pipe, a fractionating head, a direct type condenser and a receiving bottle are assembled, pressure is reduced, when the vacuum degree reaches-0.1 MPa or below, the temperature is rapidly raised, when the internal temperature is 110-.
Through testing, the preparation example obtains the required n-octyl alpha-cyanoacrylate.
Example 1
The preparation method of the medical adhesive material for rapid hemostasis comprises the following steps:
(1) according to 55 wt%: taking the alpha-n-butyl cyanoacrylate and the alpha-n-octyl cyanoacrylate in a mass ratio of 45 wt%, and fully and uniformly mixing to obtain a medical adhesive matrix for later use;
(2) placing carboxymethyl chitosan in a sealed container containing 1-methylimidazole trifluoroacetate ionic liquid (8 wt% of carboxymethyl chitosan) and herba Orostachyos juice (juice obtained by directly squeezing herba Orostachyos and 5 wt% of carboxymethyl chitosan), removing air, and introducing CO2Controlling the temperature and pressure in the closed container to be 80 ℃ and 8MPa to ensure that the CO is filled2The gas is in a supercritical state, and under the condition that the carboxymethyl chitosan is not in contact with the ionic liquid and the anti-inflammatory active ingredient, the ionic liquid and the anti-inflammatory active ingredient are carried to modify the carboxymethyl chitosan for 10min, the pressure is relieved conventionally to obtain the required modified carboxymethyl chitosan, and the modified carboxymethyl chitosan is dried for standby;
(3) according to the following steps: 10, slowly adding the modified carboxymethyl chitosan into the medical gel matrix, fully stirring until the system is in a gel state, and conventionally sterilizing to obtain the medical gel.
Example 2
The preparation method of the medical adhesive material for rapid hemostasis comprises the following steps:
(1) according to 50 wt%: taking the alpha-n-butyl cyanoacrylate and the alpha-n-octyl cyanoacrylate in a mass ratio of 50wt% and fully mixing uniformly to obtain a medical adhesive matrix for later use;
(2) placing carboxymethyl chitosan in a sealed container containing 1-methylimidazole trifluoroacetate ionic liquid (5 wt% of carboxymethyl chitosan) and herba Orostachyos juice (juice obtained by directly squeezing herba Orostachyos and accounting for 3 wt% of carboxymethyl chitosan), removing air, and introducing CO into the container2Controlling the temperature and pressure in the closed container to be 80 ℃ and 8MPa to ensure that the CO is filled2Gas processingCarrying the ionic liquid and the anti-inflammatory active ingredient to modify the carboxymethyl chitosan for 10min under the condition of a supercritical state and under the condition that the carboxymethyl chitosan is not in contact with the ionic liquid and the anti-inflammatory active ingredient, and carrying out conventional pressure relief to obtain the required modified carboxymethyl chitosan, and drying for later use;
(3) according to the following steps of 3: 10, slowly adding the modified carboxymethyl chitosan into the medical gel matrix, fully stirring until the system is in a gel state, and conventionally sterilizing to obtain the medical gel.
Example 3
The preparation method of the medical adhesive material for rapid hemostasis comprises the following steps:
(1) according to 60 wt%: taking the alpha-n-butyl cyanoacrylate and the alpha-n-octyl cyanoacrylate in a mass ratio of 40 wt% and fully mixing uniformly to obtain a medical adhesive matrix for later use;
(2) placing carboxymethyl chitosan in a sealed container containing 1-methylimidazole trifluoroacetate ionic liquid (10 wt% of carboxymethyl chitosan) and herba Orostachyos juice (juice obtained by directly squeezing herba Orostachyos and accounting for 8wt% of carboxymethyl chitosan), removing air, and introducing CO into the container2Controlling the temperature and pressure in the closed container to be 80 ℃ and 8MPa to ensure that the CO is filled2The gas is in a supercritical state, and carries the ionic liquid and the anti-inflammatory active ingredient to modify the carboxymethyl chitosan for 10min under the condition that the carboxymethyl chitosan is not in contact with the ionic liquid and the anti-inflammatory active ingredient, the pressure is conventionally relieved, the required modified carboxymethyl chitosan is obtained, and the modified carboxymethyl chitosan is dried for standby;
(3) according to the following steps of 8: 10, slowly adding the modified carboxymethyl chitosan into the medical gel matrix, fully stirring until the system is in a gel state, and conventionally sterilizing to obtain the medical gel.
Comparative example 1
The preparation method of the medical gel material according to the present comparative example is the same as that of example 1, except that the carboxymethyl chitosan is not modified in the step (2).
Comparative example 2
Comparative example a medical gel material was prepared as in example 1, except that the carboxymethyl chitosan was not modified in the step (2), and in the step (3), the ionic liquid and the anti-inflammatory active ingredient were added in equal amounts.
Comparative example 3
Comparative example a medical gel material was prepared as in example 1, except that the carboxymethyl chitosan was not modified in the step (2) and an equal amount of the ionic liquid was added in the step (3).
Comparative example 4
The medical adhesive material of the comparative example is only alpha-n-butyl cyanoacrylate and alpha-n-octyl cyanoacrylate, and the compounding ratio and the preparation method of the medical adhesive material are the same as those of example 1.
Examples of the experiments
1. Polymerization Properties
The polymerization performance of the medical adhesive materials prepared in the above examples 1 to 3 and comparative examples 1 to 4 was tested, and the polymerization time of the medical adhesive material was tested, and whether the viscosity performance of the material meets the medical standard was tested, and the test results are shown in table 1 below.
TABLE 1 polymerization Properties of the medical adhesive materials
Numbering Polymerization time/s Viscosity of polymerization
Example 1 1-2 Qualified
Example 2 1-2 Qualified
Example 3 1-2 Qualified
Comparative example 1 1-3 Qualified
Comparative example 2 2-4 Qualified
Comparative example 3 1-3 Qualified
Comparative example 4 1-2 Qualified
2. Blood volume adsorption experiment
10mL of blood was placed in each of the culture dishes, and the range of spreading of the blood was adjusted to be as concentrated as possible in the middle of the culture dish.
Respectively taking 2g of the medical adhesive material prepared in the embodiment 1 and the comparative examples 1-4, spraying and covering the medical adhesive on the surface of the blood ring through a spraying operation, wherein the medical adhesive can be polymerized by itself for 1-3 seconds to form an adhesive film, observing and recording the time (not including the time of film forming and bonding) required by the medical adhesive for adsorbing all blood, and recording the final time when the medical adhesive cannot be adsorbed and does not absorb blood any more, wherein the experimental result is shown in the following table 2.
TABLE 2 blood volume adsorption test results
Numbering Whether all are adsorbed (Total/maximum) adsorption time
Example 1 Is that 4s
Comparative example 1 Is that 10s
Comparative example 2 Is that 9s
Comparative example 3 Is that 12s
Comparative example 4 Whether or not 9s
The above data show that the medical adhesive material can realize the hemostatic effect while being bonded by adding the carboxymethyl chitosan with the hemostatic function, and further modify the performance of the carboxymethyl chitosan by selecting the ionic liquid modification mode, so that the hemostatic speed is further improved, the rapid hemostatic effect is realized, and the hemostatic performance of the material is basically not influenced by adding the ionic liquid. However, the addition of the orostachys sieboldii juice, which is an anti-inflammatory active ingredient, not only imparts anti-inflammatory properties to the medical adhesive material, but also helps to improve the hemostatic properties of the medical adhesive material.
3. Animal hemostasis test
25 rabbits having similar weights were selected and randomly divided into 5 groups of 5 rabbits, each rabbit was cut off the left ear marginal vein, the right ear marginal artery and two thirds of the left hind limb femoral artery, freely bleeded for 10s, and after 10s, each rabbit was sprayed with the medical adhesive material prepared in experimental example 1 and comparative examples 1 to 4, and was self-filmed after being pressed for 1 to 2s, and the hemostatic time (including no time for film-forming adhesion) in each experimental group was observed and recorded in the following table 3.
TABLE 3 fast hemostasis time results for each experimental group
Figure GDA0002796361130000101
Therefore, the medical adhesive material can realize rapid hemostasis.
4. Anti-inflammatory Properties
The medical adhesive material prepared in the above example 1 was sprayed on the inflamed wound surface, and after self-adhesion to form a film, the inflamed condition of the wound surface was observed. Observation proves that the medical adhesive material has certain anti-inflammatory effect due to the addition of the orostachys fimbriatus juice with anti-inflammatory effect.
The above embodiments of the present invention are described in detail, and the principle and the implementation of the present invention are explained by applying specific embodiments, and the above description of the embodiments is only used to help understanding the method of the present invention and the core idea thereof; meanwhile, for a person skilled in the art, according to the idea of the present invention, there may be variations in the specific embodiments and the application scope, and in summary, the content of the present specification should not be construed as a limitation to the present invention.

Claims (8)

1. The preparation method of the anti-inflammatory rapid hemostatic medical adhesive material is characterized by comprising the following steps:
(1) get
Figure 856487DEST_PATH_IMAGE001
N-butyl cyanoacrylate and
Figure 367103DEST_PATH_IMAGE001
uniformly mixing n-octyl cyanoacrylate to obtain a medical adhesive matrix for later use;
(2) placing carboxymethyl chitosan in a sealed container containing ionic liquid and antiinflammatory active component, removing air, and introducing CO into the container2Controlling the temperature and pressure in the closed container to make CO2The gas is in a supercritical state, and under the condition that the carboxymethyl chitosan is not in contact with the ionic liquid and the anti-inflammatory active ingredient, the ionic liquid and the anti-inflammatory active ingredient are carried to carry out modification treatment on the carboxymethyl chitosan, so that the carboxymethyl chitosan to be modified is obtained;
(3) slowly adding the modified carboxymethyl chitosan into the medical gel matrix, fully stirring until the system is in a gel state, and sterilizing to obtain the medical gel matrix;
wherein in the step (2), the addition amount of the ionic liquid accounts for 5-10wt% of the mass of the carboxymethyl chitosan;
in the step (2), the ionic liquid comprises 1-methylimidazole trifluoroacetate.
2. The method for preparing an anti-inflammatory rapid hemostatic medical adhesive material according to claim 1, wherein in the step (1), the material is prepared by
Figure 881261DEST_PATH_IMAGE001
N-butyl cyanoacrylate and
Figure 10891DEST_PATH_IMAGE001
the mass ratio of the n-octyl cyanoacrylate is 50-60 wt%: 40-50 wt%.
3. The method for preparing an anti-inflammatory rapid hemostatic medical adhesive material according to claim 1, wherein in the step (2), the anti-inflammatory active ingredient is herba orostachyos juice.
4. The method for preparing an anti-inflammatory rapid hemostatic medical adhesive material according to claim 3, wherein in the step (2), the anti-inflammatory active ingredient is added in an amount of 3-8wt% based on the mass of the carboxymethyl chitosan.
5. The method for preparing an anti-inflammatory rapid hemostatic medical adhesive material according to claim 1, wherein in the step (2), the temperature in the closed container is controlled to be 80-120 ℃ and the pressure is controlled to be 8-10 MP.
6. The preparation method of the anti-inflammatory rapid hemostatic medical adhesive material according to claim 1, wherein in the step (3), the mass ratio of the modified carboxymethyl chitosan to the medical adhesive matrix is 3-8: 10.
7. an anti-inflammatory rapid hemostatic medical adhesive material prepared by the method of any one of claims 1-6.
8. Use of the anti-inflammatory rapid hemostatic medical gel material of claim 7 for the preparation of a hemostatic material.
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