CN110917385A - Self-repairing quick-sealing medical adhesive and preparation method thereof - Google Patents
Self-repairing quick-sealing medical adhesive and preparation method thereof Download PDFInfo
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
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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
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- A61L2400/04—Materials for stopping bleeding
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Abstract
The invention discloses self-repairing quick-sealing medical adhesive and a preparation method thereof. The medical adhesive is formed by two components which are covalently crosslinked after being physically mixed by a mixing tool. Wherein the first component is composed of an esterified modified aldehyde-based polymer, and the second component is composed of an amino-modified polymer. The invention can adjust the gelling time, the breaking strength and the adhesive force to the wound of the medical adhesive by adjusting the proportion and the concentration of the esterified group, the aldehyde group and the amino group. The invention can adjust the viscosity and density of the medical gel before gelling by adjusting the concentrations of the first component and the second component, and can reduce the influence of blood. The medical adhesive has high amino content and certain bacteriostatic ability. When the medical glue is glued, a dynamic key can be formed, and the medical glue has a certain self-repairing function. Therefore, the medical adhesive has the effects of quickly and efficiently stopping bleeding, self-repairing and inhibiting bacteria.
Description
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to self-repairing quick-sealing medical adhesive and a preparation method thereof.
Background
In surgical operations, the ability to rapidly, effectively and safely stop bleeding is one of the key factors in ensuring the success of the operation. The excellent medical adhesive can control wound surface bleeding or tissue fluid, ensure clear operation visual field, improve operation efficiency and accelerate postoperative recovery of patients.
Various medical glues have been developed at home and abroad, mainly including animal-derived medical glues, semi-synthetic medical glues and synthetic medical glues, wherein the animal-derived medical glues are fibrin glues containing thrombin (such as double embroidery glue and curdlan) and collagen and gelatin (such as fluid gelatin (surgiflo)), the semi-synthetic medical glues are gelatin-resorcinol formaldehyde/glutaraldehyde (such as Gluetiss) and bovine serum albumin/glutaraldehyde (such as Bioglue), the synthetic glues include α -cyanoacrylates (such as Kangpai special medical glue and dolomitic medical glue) and polyethylene glycols (such as Duraseal and Adherus).
At present, a rapid hemostatic gel is disclosed, for example, chinese patent document CN106620825A discloses a two-component rapid hemostatic gel and its application, wherein the gel is composed of an aldehyde-based natural polysaccharide solution with a mass concentration of 1-20% and an amino-modified natural biopolymer solution with a mass concentration of 1-20% in a volume ratio of 1: 0.1-1; the invention can increase the viscosity of the gel and reduce the gel forming time by increasing the aldehyde group content in the natural polysaccharide and increasing the concentration of the aldehyde-based natural polysaccharide solution. The gelling time can be reduced by increasing the grafting amount of amino groups in the amino-modified natural biopolymer and the concentration of the amino-modified natural polymer solution. The modified natural polysaccharide and natural biological polymer are adopted, so that the biological safety is good, the use method is simple, the medical hemostatic material can be used in the field of medical hemostasis, and the gel forming hemostasis can be realized within 10-600 seconds. The hemostatic gel disclosed by the patent has a self-repairing function and also has a certain effect of preventing blood from being affected, but the transaction time of the hemostatic gel is more than 10 seconds.
Chinese patent document CN108187130A discloses an agent for biological injury or hemostasis, which comprises a natural biological macromolecule modified by a photoresponsive crosslinking group, and application of the natural biological macromolecule modified by the photoresponsive crosslinking group and a method for injury repair or hemostasis by using the natural biological macromolecule modified by the photoresponsive crosslinking group. The biological viscosity of the light-operated biological glue can be controlled by light activation. Before the excitation of illumination, the biological glue does not contain aldehyde group and can not react with amino on the tissue, so that the tissue has no viscosity. After the light is activated, aldehyde groups are generated on the molecules of the o-nitrobenzyl-type plate polishing machine and can quickly react with amino groups on tissues, so that the biological glue has better biological viscosity. The viscosity of the biological glue can be increased by increasing the concentration of natural biological macromolecules modified by the o-nitrobenzyl optical trigger. The method adopts the natural biological macromolecules modified by the photoresponse crosslinking groups and the natural biological macromolecules modified by the o-nitrobenzyl light trigger, has good biological safety, is simple to use, can be used in the fields of medical hemostasis and tissue adhesion repair, can form gel within 1-30 seconds, and realizes rapid hemostasis and tissue repair. This patent has avoided the influence of blood to hemostatic reagent to a certain extent through the light conversion principle, has increased the adhesive capacity to wet attitude tissue to can become the colloid fast, it is fast to stanch. However, the biological injury or hemostasis agent disclosed in the patent needs ultraviolet light for excitation, so that the application of the biological injury or hemostasis agent to tissues which cannot be irradiated by the ultraviolet light in a human body is limited, and the biological injury or hemostasis agent has limitations.
In conclusion, there is a clinical urgent need for a medical adhesive which has good biocompatibility, can be quickly gelled, has high adhesion to wet tissues, does not require light, and has high breaking strength.
Disclosure of Invention
The invention aims to provide the medical adhesive which is formed by in-situ crosslinking, has mild reaction conditions, can be quickly gelatinized, has high adhesion in a wet tissue, higher rupture strength and good biocompatibility and does not need illumination.
The invention also provides a preparation method of the medical adhesive, which is simple and convenient to operate and implement.
The invention is realized by the following technical scheme.
The self-repairing quick-sealing medical adhesive comprises a first component consisting of esterified and modified aldehyde-based polymers and a second component consisting of amino-modified polymers.
The amino-containing modified polymer in the self-repairing quick-sealing medical adhesive is one or more of amino-modified polysaccharide, amino-modified protein and amino-modified polyamino acid.
The molecular weight of the amino-containing modified polymer in the self-repairing quick-sealing medical adhesive is 3KDa-3000 KDa.
The molar content of amino in the amino-containing modified polymer in the self-repairing quick-sealing medical adhesive is 40-80%.
The main chain of the amino modified polysaccharide in the self-repairing quick-sealing medical gel is one or more of hyaluronic acid, sodium alginate, chitosan, glucan, agarose, carboxymethyl cellulose or chondroitin sulfate.
The amino modified protein main chain in the self-repairing quick-sealing medical adhesive is one or more of gelatin, collagen, fibroin and fibrin.
The amino modified polyamino acid main chain in the self-repairing quick-sealing medical adhesive is one or two of polyaspartic acid and polylysine.
The esterified aldehyde macromolecule esterified functional group in the self-repairing quick-sealing medical adhesive is selected from succinimide glutarate ester group (SG), succinimide sebacate ester group (-SSeb), succinimide succinate group (-SS), succinimide propionate group (-SPA), succinimide acetate group (-SCM), succinimide carbonate group (-SC) and the like.
The aldehyde group macromolecule main chain modified by esterification in the self-repairing quick-sealing medical adhesive is one or two of hyaluronic acid and sodium alginate.
The molecular weight of the esterified modified aldehyde-based polymer in the self-repairing quick-sealing medical adhesive is 3KDa-3000 KDa.
The molar content of aldehyde groups of the esterified and modified aldehyde-based macromolecules in the self-repairing quick-sealing medical adhesive is 40-80%.
The molar content of esterified groups of the esterified modified aldehyde-based polymer in the self-repairing quick-sealing medical adhesive is 40-80%.
The invention also provides a preparation method of the self-repairing quick-sealing medical adhesive, which is characterized by comprising the following steps: dissolving the first component in a buffer solution with the pH value of 4-7.4 to obtain a solution A, dissolving the second component in a buffer solution with the pH value of 7.4-10 to obtain a solution B, mixing the solution A and the solution B, and performing a crosslinking reaction on the first component and the second component to form the medical adhesive.
In the preparation method, the concentration of the macromolecules containing amino groups in the solution A is 2-20% (mass fraction), and the concentration of the aldehyde polysaccharide modified by catechol in the solution B is 2-20% (mass fraction).
In the above preparation method, the solution A and the solution B were mixed in a volume ratio of 1: 1 using a double syringe.
In the preparation method, the buffer solution is composed of one or more of phosphate, carbonate, phosphoric acid, acetic acid, hydrochloride, hydrochloric acid, sodium hydroxide and the like. The specific components of the buffer solution can be selected according to the stability of the components in the buffer solution and the physicochemical properties and biocompatibility of the formed medical gel, and the buffer solution also does not contain harmful or toxic solvents, usually water is selected as the solvent, and the osmotic pressure of the buffer solution is the same as or similar to that of the blood of organisms.
Compared with the prior art, the invention has the beneficial effects that:
1. the self-repairing quick-sealing medical adhesive can be used for in-situ adhesive forming, illumination is not needed, and damage to tissues caused by illumination is avoided.
2. The self-repairing quick-sealing medical adhesive disclosed by the invention utilizes a mode of reacting an esterified functional group, an aldehyde group and an amino group, so that the medical adhesive is high in adhesive forming speed and adhesive forming breaking strength, the adhesive can be formed in 1 second at the fastest speed, the highest breaking strength is up to 280mmHg, and quick hemostasis can be realized.
3. The self-repairing quick-sealing medical adhesive increases the viscosity and density of the medical adhesive by utilizing the esterified and modified aldehyde-based polymer and the amino-modified polymer, thereby reducing the influence of blood in the spraying process and enabling the medical adhesive to be tightly attached to a wound.
4. The self-repairing quick-sealing medical adhesive can adjust the adhesion of the medical adhesive to a wound by adjusting the content of aldehyde groups and esterified groups in the medical adhesive.
5. The self-repairing quick-sealing medical adhesive contains dynamic chemical bonds, has a self-repairing function, can be self-repaired after the medical adhesive is damaged, prolongs the service life of the material and reduces the damage of accidental damage to tissues.
Description of the drawings:
1. fig. 1 is a sample of self-healing quick-seal medical glue.
2. Fig. 2 is a schematic diagram of self-repairing quick-sealing medical adhesive.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to the following examples. The following examples are given based on the technical solutions of the present invention, further provide detailed embodiments and specific procedures of the present invention, and will help understanding of the present invention, but the scope of the present invention is not limited to the following examples. The methods used in the examples are conventional methods unless otherwise specified.
Example 1
Dissolving 1g of aminated gelatin with molecular weight of 15-25KDa and amino molar ratio of 80% in 10ml of phosphate buffer solution with pH value of 7.4, and mechanically stirring to obtain uniform solution A.
Dissolving 1.25g of esterified modified aldehyde sodium alginate with the molecular weight of 80-120KDa, the aldehyde group molar ratio of 80% and the succinimide glutarate group (SG) molar ratio of 80% in 10ml of phosphate buffer solution with the pH value of 7.4, and mechanically stirring to obtain a uniform solution, thereby obtaining a solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Example 2
0.2g of aminated hyaluronic acid with molecular weight of 2500-3000KDa and amino molar ratio of 40% is dissolved in 10ml of borate buffer solution with pH value of 10, and the solution is mechanically stirred and dissolved into uniform solution to obtain solution A.
Dissolving 0.2g of esterification modified aldehyde chitosan with 2000-3000KDa, 40 percent of aldehyde group molar ratio and 40 percent of succinimide sebacate group (-SSeb) molar ratio in 10ml of phosphoric acid solution with pH value of 4, and mechanically stirring to obtain uniform solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Example 3
Dissolving 2g of aminated polylysine with molecular weight of 3-10KDa and amino molar ratio of 60% in 10ml of carbonate buffer solution with pH value of 8.5, and mechanically stirring to obtain uniform solution A.
Dissolving 2g of esterified and modified aldehyde glucan with the molecular weight of 3-5KDa, the molar ratio of aldehyde groups of 60 percent and the molar ratio of succinimidyl succinate (-SS) of 60 percent in 10ml of acetic acid solution with the pH value of 5.5, and mechanically stirring to dissolve the mixture into uniform solution to obtain solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Example 4
Dissolving 2g of aminated modified sodium alginate with molecular weight of 80-120KDa and amino molar ratio of 80% in 10ml of physiological saline solution with pH value of 7.4, and mechanically stirring to obtain uniform solution A.
Dissolving 2g of esterified and modified aldehyde hyaluronic acid with the molecular weight of 1000-2000KDa, the molar ratio of aldehyde groups of 80 percent and the molar ratio of succinimidyl propionate groups (-SPA) of 80 percent in 10ml of physiological saline solution with the pH value of 7.4, and mechanically stirring to dissolve the mixture into uniform solution to obtain solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Example 5
0.5g of chitosan subjected to amination modification and having the molecular weight of 1000-2000KDa and the amino molar ratio of 80 percent and 0.5g of dextran subjected to amination modification and having the molecular weight of 5-7.5KDa and the amino molar ratio of 40 percent are dissolved in 10ml of phosphate buffer solution with the pH value of 7.4, and the solution A is obtained by mechanically stirring and dissolving the solution into uniform solution.
0.5g of urethane modified aldehyde agarose with the molecular weight of 100-200KDa, the molar ratio of aldehyde groups of 80 percent and the molar ratio of succinimide acetate groups (-SCM) of 60 percent is added, 0.5g of esterification modified aldehyde carboxymethyl cellulose with the molecular weight of 6.4-17KDa, the molar ratio of aldehyde groups of 40 percent and the molar ratio of succinimide carbonate groups (-SC) of 60 percent is added, and finally 0.25g of esterification modified aldehyde chondroitin sulfate with the molecular weight of 20-50KDa, the molar ratio of aldehyde groups of 60 percent and the molar ratio of succinimide succinate groups (-SS) of 60 percent is added and dissolved in 10ml of phosphate buffer solution with the pH value of 7.4, and the solution B is obtained by mechanical stirring and dissolving into uniform solution.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Example 6
0.1g of amination-modified collagen with the molecular weight of 100-300KDa and the amino molar ratio of 40 percent, 0.05g of amination-modified polyaspartic acid with the molecular weight of 3-10KDa and the amino molar ratio of 60 percent, and 0.05g of amination-modified agarose with the molecular weight of 30-50KDa and the amino molar ratio of 80 percent are dissolved in 10ml of sodium hydroxide solution with the pH value of 10, and the solution is mechanically stirred and dissolved into uniform solution to obtain solution A.
0.1g of esterified modified aldehyde group hyaluronic acid with the molecular weight of 1000-2000KDa, the molar ratio of aldehyde groups of 60 percent and the molar ratio of succinimide glutarate ester groups (SG) of 40 percent and 0.1g of esterified modified aldehyde group chondroitin sulfate with the molecular weight of 2000-3000KDa, the molar ratio of aldehyde groups of 40 percent and the molar ratio of succinimide sebacate ester groups (-SSeb) of 80 percent are dissolved in 10ml of hydrochloric acid solution with the pH value of 4, and the solution is mechanically stirred and dissolved into uniform solution to obtain solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Example 7
Dissolving 1g of amination modified fibroin with molecular weight of 10-30KDa and amino molar ratio of 40 percent and 1g of amination modified fibrin with molecular weight of 100-200KDa and amino molar ratio of 60 percent in 10ml of carbonate buffer solution with pH value of 8.5, and mechanically stirring to dissolve into uniform solution to obtain solution A.
Dissolving 0.5g of esterified modified aldehyde sodium alginate with the molecular weight of 50-80KDa, the molar ratio of aldehyde groups of 40 percent and the molar ratio of succinimide succinate (-SS) of 60 percent and 1.5g of esterified modified aldehyde carboxymethyl chitosan with the molecular weight of 10-20KDa, the molar ratio of aldehyde groups of 60 percent and the molar ratio of succinimide propionate (-SPA) of 40 percent in 10ml of acetic acid solution with the pH value of 5.5, and mechanically stirring to dissolve the mixture into uniform solution to obtain solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Example 8
0.2g of amino-modified carboxymethyl cellulose with molecular weight of 3-10KDa and amino molar ratio of 60%, 0.5g of amino-modified chondroitin sulfate with molecular weight of 2000-3000KDa and amino molar ratio of 80%, and 0.3g of amino-modified polylysine with molecular weight of 200-300KDa and amino molar ratio of 40% are dissolved in 10ml of physiological saline solution with pH value of 7.4, and the solution is mechanically stirred and dissolved into uniform solution to obtain solution A.
0.3g of esterified chitosan with molecular weight of 1000-2000KDa, molar ratio of aldehyde groups of 40 percent and molar ratio of succinimide acetate groups (-SCM) of 80 percent, 0.3g of esterified dextran with molecular weight of 3-5KDa, molar ratio of aldehyde groups of 60 percent and molar ratio of succinimide carbonate groups (-SC) of 40 percent, and 0.4g of esterified agarose with molecular weight of 100-200KDa, molar ratio of aldehyde groups of 80 percent and molar ratio of succinimide glutarate groups (SG) of 60 percent are dissolved in 10ml of physiological saline solution with pH value of 7.4 and dissolved into uniform solution by mechanical stirring to obtain solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Comparative example 1
Dissolving 0.05g of aminated gelatin with molecular weight of 15-25KDa and amino molar ratio of 80% in 10ml of phosphate buffer solution with pH value of 7.4, and mechanically stirring to obtain uniform solution A.
Dissolving 2.5g of esterified modified aldehyde sodium alginate with the molecular weight of 80-120KDa, the aldehyde group molar ratio of 80% and the succinimide glutarate group (SG) molar ratio of 80% in 10ml of phosphate buffer solution with the pH value of 7.4, and mechanically stirring to obtain a uniform solution, thereby obtaining a solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Comparative example 2
Dissolving 1g of aminated gelatin with molecular weight of 1-2KDa and amino molar ratio of 80% in 10ml of phosphate buffer solution with pH value of 7.4, and mechanically stirring to obtain uniform solution A.
Dissolving 1.25g of esterified modified aldehyde sodium alginate with the molecular weight of 1-2KDa, the aldehyde group molar ratio of 80 percent and the succinimide glutarate group (SG) molar ratio of 80 percent in 10ml of phosphate buffer solution with the pH value of 7.4, and mechanically stirring to dissolve the mixture into uniform solution to obtain solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Comparative example 3
1g of aminated gelatin with molecular weight of 4000-4500KDa and amino molar ratio of 80% is dissolved in 10ml of phosphate buffer solution with pH value of 7.4, and the solution is mechanically stirred and dissolved into uniform solution to obtain solution A.
Dissolving 1.25g of esterification modified aldehyde sodium alginate with the molecular weight of 4500-5000KDa, the aldehyde group molar ratio of 80 percent and the succinimide glutarate group (SG) molar ratio of 80 percent in 10ml of phosphate buffer solution with the pH value of 7.4, and mechanically stirring to obtain uniform solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
Comparative example 4
Dissolving 1g of aminated gelatin with molecular weight of 15-25KDa and amino molar ratio of 20% in 10ml of phosphate buffer solution with pH value of 7.4, and mechanically stirring to obtain uniform solution A.
Dissolving 1.25g of esterified modified aldehyde sodium alginate with the molecular weight of 80-120KDa, the aldehyde group molar ratio of 30% and the succinimide glutarate group (SG) molar ratio of 30% in 10ml of phosphate buffer solution with the pH value of 7.4, and mechanically stirring to obtain a uniform solution, thereby obtaining a solution B.
And respectively filling the solution A and the solution B into two syringes of the duplex syringes, and mixing and atomizing the two syringes to form the medical adhesive.
In order to test the medical glue of the invention, the following performance test experiments were performed.
And (3) detection of gelling time:
1.1 the preparation method of the medical glue comprises the following steps:
dissolving the first component in a buffer solution with the pH value of 7.4-10 to obtain a solution A, dissolving the second component in a buffer solution with the pH value of 4-7.4 to obtain a solution B, filling the solution A and the solution B into a two-component liquid mixer, atomizing and spraying the solution A and the solution B, and carrying out a crosslinking reaction on the first component and the second component to form the medical adhesive.
1.2 a gelling time detection method:
and (3) uniformly pushing the duplex syringe, mixing the solution A and the solution B by a two-component liquid mixer, spraying the mixture onto a watch glass with certain anticoagulation pig blood, starting timing at the same time until gel is completely formed (no flowing liquid), and recording the time, namely the gelling time.
And (3) detecting the fracture strength: besides the gelling time, the breaking strength of the medical adhesive is an important index of the material, and reflects the mechanical property of the medical adhesive in the use process. The detection method comprises the following steps:
(1) a hole with the diameter of about 0.16cm +/-0.02 cm is formed in a fresh pig casing for later use.
(2) And (3) installing the solution A and the solution B on a two-component liquid mixer according to a preparation method of a sample to be detected in the gelling time detection.
(3) Pushing the two-component liquid mixer to form medical glue with a specified thickness on the holes of the casing, uniformly pressurizing the lower part of the casing after complete gel is formed until the gel is damaged or peeled off, and recording the maximum pressure number.
And (3) detecting the bonding strength: pigskin was selected as a model for studying the adhesiveness of medical glues. The fat layer of the pigskin was first scraped off until the dermis layer was exposed, and the pigskin was cut into small pieces 1cm wide and 3 cm long. The small pieces were first soaked in anticoagulated pig blood for 5s, solution A was applied to a 1cm by 1cm area of one pig skin, solution B was applied to a 1cm by 1cm area of the other pig skin, and the applied areas of the two pig skins were staggered and applied with a weight of 50g for 1 hour (to ensure complete adhesion). Then, 1cm of the two ends of the sample were fixed on a material testing machine to conduct a tensile test at a tensile speed of 10 mm/min.
Test results
The gel time, breaking strength and adhesive strength of the medical glues of the examples and comparative examples are shown in table 1 below.
Conclusion
1. The medical glue has the glue forming time within 5s under the condition of blood influence, is faster than that of comparative examples 1, 3 and 4, can quickly play a role in hemostasis and avoids excessive blood loss.
2. The medical adhesive has the adhesive strength of more than 180mmHg, is higher than that of comparative examples 1, 2, 3 and 4, is higher than the arterial pressure of a human body (less than 140 mmHg), can resist blood impact after wound sealing, and plays a role in effectively protecting the wound.
3. When anticoagulated pig blood is present in the medical adhesive during the experiment, the wet bonding strength is more than 14kPa, is higher than that of comparative examples 1, 2, 3 and 4, and is also higher than that of the commercially available fibrin adhesive by 13.54 kPa, so that the medical adhesive can have a strong bonding effect on wet wounds, and the influence of blood on the medical adhesive is avoided.
Further, in order that the medical adhesive can be applied to the human body, the following safety test was performed.
Cytotoxicity test:
the solution A and the solution B are installed on a two-component liquid mixer according to a preparation method of a sample to be detected in gelling time detection, the solution A and the solution B are injected into a watch glass to form gel, besides swelling absorption capacity, the solution A and the solution B are extracted according to the proportion of 0.1g and 1.0ml of extraction medium, the extraction medium is serum-containing MEM culture medium, the extraction temperature is 37 +/-1 ℃, the extraction time is 24 +/-2 hours, the extraction liquid is taken as test liquid, the test method specified in GB/T16886.5-2017 is carried out, and the grading is carried out according to United states pharmacopoeia.
Intradermal reaction test:
according to the preparation method of the sample to be detected in the gelling time detection, the solution A and the solution B are installed on a two-component liquid mixer and injected into a watch glass to form gel, besides swelling absorption capacity, leaching is carried out according to the proportion of 0.1g and 1.0ml of leaching medium, the leaching medium is physiological saline and cottonseed oil, the leaching temperature is 37 +/-1 ℃, the leaching time is 72 +/-2 hours, and the leaching liquid is taken as a test solution. The test solution was collected and subjected to the test method defined in GB/T16886.10-2017.
Acute systemic toxicity test:
the solution A and the solution B are installed on a two-component liquid mixer according to a preparation method of a sample to be detected in gelling time detection, the two-component liquid mixer is injected into a watch glass to form gel, besides swelling absorption capacity, the two-component liquid mixer is extracted according to the proportion of 0.1g and 1.0ml of extraction medium, the extraction medium is physiological saline and cottonseed oil, the extraction temperature is 37 +/-1 ℃, the extraction time is 72 +/-2 hours, and the extraction liquid is taken according to an intraperitoneal injection test method specified in GB/T16886.11-2011.
The results of cytotoxicity test, intradermal reaction test and acute systemic toxicity test are shown in Table 2, and the test results show that the invention is applicable to the treatment of various tumors
The medical adhesive has no cytotoxicity, toxicity and irritation, and has high safety.
Finally, it should be noted that the above disclosure is only for a few specific embodiments of the present invention, but the present invention is not limited thereto, and any variations that can be made by those skilled in the art are intended to fall within the scope of the present invention.
Claims (9)
1. The self-repairing quick-sealing medical adhesive comprises a first component consisting of esterified and modified aldehyde-based polymers and a second component consisting of amino-modified polymers.
2. The self-repairing quick-sealing medical adhesive of claim 1, which is characterized in that: the amino-containing modified polymer is one or more of amino-modified polysaccharide, amino-modified protein and amino-modified polyamino acids.
3. The self-repairing quick-sealing medical adhesive of claim 1, which is characterized in that: the molecular weight of the amino-containing modified polymer is 3KDa-3000KDa, and the molar content of amino is 40-80%.
4. The self-repairing quick-sealing medical adhesive as claimed in claim 2, wherein: the main chain of the amino modified polysaccharide is one or more of hyaluronic acid, sodium alginate, chitosan, glucan, agarose, carboxymethyl cellulose or chondroitin sulfate; the amino modified protein main chain is one or more of gelatin, collagen, fibroin and fibrin; the main chain of the amino modified polyamino acid is one or two of polyaspartic acid and polylysine.
5. The self-repairing quick-sealing medical adhesive of claim 1, which is characterized in that: the esterified functional group of the aldehyde macromolecule is selected from succinimide glutarate group (SG), succinimide sebacate group (-SSeb), succinimide succinate group (-SS), succinimide propionate group (-SPA), succinimide acetate group (-SCM), succinimide carbonate group (-SC) and the like.
6. The self-repairing quick-sealing medical adhesive of claim 1, which is characterized in that: the esterified and modified aldehyde group polymer main chain is one or two of hyaluronic acid and sodium alginate, the molecular weight of the esterified and modified aldehyde group polymer main chain is 3KDa-3000KDa, wherein the molar content of the aldehyde group is 40-80%, and the molar content of the esterified group is 40-80%.
7. A method for preparing the self-repairing quick-sealing medical adhesive as claimed in any one of claims 1 to 6, wherein the method comprises the following steps: dissolving the first component in a buffer solution with the pH value of 4-7.4 to obtain a solution A, dissolving the second component in a buffer solution with the pH value of 7.4-10 to obtain a solution B, mixing the solution A and the solution B, and performing a crosslinking reaction on the first component and the second component to form the medical adhesive.
8. The method according to claim 7, wherein the concentration of the amino group-containing polymer in the solution A is 2 to 20% (mass fraction), and the concentration of the catechol-modified aldehyde polysaccharide in the solution B is 2 to 20% (mass fraction).
9. The method of claim 8, wherein: the buffer solution is composed of one or more of phosphate, carbonate, phosphoric acid, acetic acid, hydrochloride, hydrochloric acid, sodium hydroxide and the like, the specific components of the buffer solution can be selected according to the stability of the components in the buffer solution, the physicochemical property and the biocompatibility of the formed medical adhesive, and the buffer solution also does not contain harmful or toxic solvents, water is usually selected as the solvent, and the osmotic pressure of the buffer solution is the same as or similar to the osmotic pressure of the blood of organisms.
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