CN108159483B - Adhesive sealant for rapid surgical operation - Google Patents

Adhesive sealant for rapid surgical operation Download PDF

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CN108159483B
CN108159483B CN201810115515.4A CN201810115515A CN108159483B CN 108159483 B CN108159483 B CN 108159483B CN 201810115515 A CN201810115515 A CN 201810115515A CN 108159483 B CN108159483 B CN 108159483B
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CN108159483A (en
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甘少磊
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Jiangxi Proton Biotechnology 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
    • A61L24/046Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001Use of materials characterised by their function or physical properties
    • A61L24/0031Hydrogels or hydrocolloids
    • 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
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10Polypeptides; Proteins
    • A61L24/104Gelatin

Abstract

A rapid surgical adhesive sealant is a two-component in situ hydrogel sealant designed to prevent leakage and infection at the surgical site after surgery. It includes: multi-arm polyethylene glycol (multi-arm PEG-SG) powder with bis glutarate-hydroxysuccinimide ester modification (first component) in a first container (closed tray); a modified gelatin solution (second component) in a second container (sealed plastic tubing or syringe); and a medical applicator stick (medical cotton swab or foamed polyethylene). When the hydrogel sealant is used, the second container is firstly opened, the second component solution is extruded/injected into the tray of the first container, the tail end of the smearing rod is used for quickly stirring, after the first component powder is completely dissolved, the adhesive sealant is smeared to an operation part from the head end of the smearing rod, and the firm hydrogel sealant can be formed after waiting for a moment.

Description

Adhesive sealant for rapid surgical operation
Technical Field
The invention relates to a medical adhesive, in particular to a polyethylene glycol (PEG) hydrogel medical adhesive.
Background
Compared with the traditional surgical suture sealing system (such as suture, hemostatic gauze, hemostatic sponge, polysaccharide hemostatic powder and the like), the in-situ hydrogel sealing agent gradually stands out due to the advantages, and is more and more concerned by people.
First, the in situ hydrogel sealing adhesive exists as a liquid precursor without a fixed shape prior to forming the gel, acting directly at the site of action by simple injection or coating. The delivery is simple and quick and easy to handle, and its unique amorphous liquid precursor properties also give it the ability to better contact the site of action, making it more firmly attached to the site of action. Therefore, the in-situ hydrogel adhesive agent is not limited to the irregular shape of the action site of the material like the traditional biomedical suture sealing material, so that the use of the traditional material is greatly limited and the use effect of the traditional material is reduced;
second, in situ hydrogel blocking adhesives are capable of rapidly forming hydrogel solids with fixed shapes within a short period of time (usually within minutes) after reaching the site of action as a liquid precursor. In the process, the product does not cause serious damage to human bodies and is nontoxic and harmless to the human bodies;
in addition, most of the components of the solid hydrogel formed after the in-situ hydrogel sealing adhesive is applied to the action site are water, and macromolecules forming the hydrogel framework are hydrophilic molecules with good biocompatibility, so that the formed hydrogel has a microenvironment very similar to a matrix for cell growth. Therefore, the sealant is very suitable for the growth of cells and has very positive significance for the recovery and healing of the acting site of the sealant;
in addition, the solid hydrogel formed by the in-situ hydrogel sealing adhesive has a special structure, so that the solid hydrogel can load components such as cells, factors, nutrients, medicines and the like, and the components can directly reach the action site without influencing other tissues of the body or causing waste. In addition, the special network structure of the hydrogel can effectively lock water molecules and small molecules such as factors, nutrients, medicines and the like, so that certain slow release effect is achieved on the small molecule compounds;
furthermore, a part of the hydrogel sealing adhesive material has certain antibacterial capacity due to the inherent composition. For example, some chitosan hydrogels and a part of polypeptide hydrogels can cause the material to show excellent antibacterial property due to the molecular property thereof, thereby playing the role of antibiosis and anti-inflammation on the action site of the hydrogel blocking adhesive;
finally, it has to be mentioned: after the in-situ hydrogel sealing adhesive forms solid hydrogel at an action site, the hydrogel is gradually decomposed along with healing and recovery of site tissues while the site is prevented from leaking and tissue repair is promoted. And after the tissue is completely healed, the hydrogel can be completely decomposed, and the decomposition product is non-toxic and harmless to human bodies. Finally, the decomposition products can be completely discharged from the body without causing adverse effects on the body.
For in situ hydrogels, however, we can be divided into two broad categories by the difference in the gelling mechanism of their hydrogel components: physical in situ hydrogels and chemical in situ hydrogels. Both of these in situ hydrogels can form solid hydrogels soon after reaching the site of action, but each has different advantages and disadvantages that limit their application, and the characteristics of the next two in situ hydrogels are briefly described below.
In situ physical hydrogels are those where the hydrogel precursor reaches the site of action in liquid form and then senses external physical signals (e.g.:temperature, pH, ions, etc.) to rapidly form a closed hydrogel in situ (e.g.: the PIN-PAM modified biological molecules can form hydrogel at the temperature of about 37 ℃ of a human body; some polypeptides with specific sequences are entangled under neutral pH condition through the mutual attraction of positive and negative charges to form in-situ hydrogel; the sodium alginate aqueous solution meets Ca2+Then chelation occurs, thereby forming a physical in situ hydrogel). The physical hydrogel can be formed in a very short time, and does not generate harmful stimulation to human bodies such as high temperature, peracid, over alkali and the like in the gelling process, and does not generate toxic and harmful substances to the human bodies. On the other hand, the relatively weak mechanical properties and the relatively weak tissue adhesion ability of the in situ physical hydrogel, like other physical hydrogels, limit the application and development thereof. Because the physical hydrogel is mainly formed by physical action (such as electrostatic force, hydrophobic force, hydrogen bond and the like), the hydrogel system is easily damaged, so that the hydrogel system has poor mechanical properties, is easily shed from tissues and is easily decomposed, and the development of in-situ physical hydrogel sealants is limited.
In situ chemical hydrogels, after reaching the site of action as a liquid precursor, undergo chemical reactions at the site of action (e.g., addition reactions by mixing of liquids, "click chemistry" cyclization reactions between azide groups and acetylenic bonds, and photoinitiated addition reactions) and rapidly form a chemical hydrogel solid. The hydrogel is formed by chemical reaction, so that the hydrogel generally has good mechanical properties, and compared with the physical in-situ hydrogel, the chemical in-situ hydrogel is not easy to decompose, and the effect can be fully exerted without decomposition in the middle. On the other hand, however, the chemical in situ hydrogel has its own disadvantages: firstly, chemical reaction in the gelling process may cause certain damage to action sites along with drastic changes in temperature, pH value and the like; secondly, some catalysts which are toxic to human bodies are probably needed in the gelling process; in addition, chemical reactions in the gelling process may also have some byproducts harmful to human bodies; finally, the hydrogel formed finally has very good mechanical properties, so that the shape of the hydrogel is not easy to change after gelling. These have limited the development and application of chemical in situ hydrogel sealants.
The invention aims to overcome the defects of the prior art and provide a novel disposable gel sealing adhesive which is applied to a wound after a surgical clinical operation and is expected to rapidly close the wound and prevent leakage, and the adhesive can be rapidly formed into firm gel at the wound, and the hydrogel has extremely strong tissue adhesion capacity. The gel used by the adhesive has good biodegradability, biocompatibility and safety and reliability.
Disclosure of Invention
To accomplish the above object, the present invention provides a kit for a rapid surgical adhesive sealant assembly, comprising:
a) a first component in a closed first container, said first component being a solid powder component selected from multi-armed polyethylene glycol with bis-glutarate-hydroxysuccinimide ester modification selected from two-armed polyethylene glycol, four-armed polyethylene glycol or eight-armed polyethylene glycol, preferably selected from four-armed polyethylene glycol or eight-armed polyethylene glycol,
b) a second component in a closed second container, the second component being a solution component having a solute selected from the group consisting of modified gelatin polysaccharide and a solvent for the solution component being a biological buffer solution;
c) the kit further comprises a smearing tool for mixing the first and second components and smearing the pre-gel solution;
wherein the content of the first and second substances,
the first component and the second component jointly form a formula of the rapid surgical operation bonding sealant component set, and the weight percentage of the multi-arm polyethylene glycol modified by the bis-glutarate-hydroxyl succinimide ester is 5-20%, preferably 7-15%, and most preferably 9% based on the total weight of the formula; the weight percentage of the modified gelatin polysaccharide is 0.2-3%, preferably 0.5-2%, and optimally 1%; the weight percentage of the biological buffer solution is 77-99.8%, preferably 83-92.5%, and most preferably 90%. And, when the two components are mixed, the sealant hydrogel can be rapidly and firmly applied to a surgical site.
Wherein the first container is a tray, and/or the second container is a hose or a syringe.
Wherein the biological buffer solution is selected from phosphate or borate buffer solutions.
Wherein the pH value of the buffer solution is 4 to 12, preferably 6 to 8, and optimally 7.4.
Wherein the modified gelatin polysaccharide in the second component solution is selected from the following 2 modified gelatin polysaccharides:
Figure 916304DEST_PATH_IMAGE001
cholesterol-modified gelatin polysaccharide with PEG chain, or
Figure 140612DEST_PATH_IMAGE002
Gelatin polysaccharides modified by poloxamer.
Wherein the weight average molecular weight of the modified gelatin polysaccharide before modification is 1000 to 5000 daltons, preferably 2000 to 3500, and most preferably 3000; modified gelatin polysaccharide
Figure 139792DEST_PATH_IMAGE001
The molecular weight of PEG used for modifying the gelatin polysaccharide is 1000-10000, preferably 3000-6000, most preferably 5000, and the modified gelatin polysaccharide
Figure 424142DEST_PATH_IMAGE002
The molecular weight of the poloxamer used for modifying the gelatin polysaccharide is 9840-8830, preferably 9600-9000, and most preferably 9300.
Wherein the single arm weight average molecular weight of the multi-arm PEG of the first component is 800 to 10000 daltons, preferably 2000 to 8000, and most preferably 5000.
Wherein, hemostatic drugs, antibiotic drugs, antiviral drugs or their combination are added into the first component or the second component of the rapid surgery adhesive sealant component set. The weight percentage of the added medicine is 0.01-25% based on the total weight of the formula.
Wherein a proper amount of a medical dye should be added to the first component solid powder to increase the workability of the use of the sealant.
Wherein, the medical dye added in the first component solid powder is selected from FD & C Blue 1 Blue dye.
One end of the smearing tool is used for mixing and stirring the two precursor solutions; the other end is responsible for smearing the evenly mixed solution to the operation position so as to form gel at the operation position and achieve the sealing effect.
Wherein the modified gelatin polysaccharide of the second component
Figure 774352DEST_PATH_IMAGE001
The preparation method of (a) is shown in the following scheme 1:
the method specifically comprises the following steps: reacting 1 equivalent of cholesterol and 2 equivalents of methylbenzenesulfonyl chloride in pyridine at room temperature for 12 hours, extracting and evaporating to dryness by using dichloromethane and water to obtain a white solid, dissolving the white solid in pyridine, adding 1 equivalent of PEG, reacting at room temperature, and purifying after the reaction is finished. Dissolving the obtained sample and 1.5 equivalent of p-nitrophenyl chloroformate in pyridine, purifying, reacting with certain amount of gelatin polysaccharide in DMSO, and purifying to obtain modified gelatin polysaccharide of second component
Figure 802351DEST_PATH_IMAGE001
Figure 983934DEST_PATH_IMAGE003
Wherein: TsCL is methyl benzene sulfonyl chloride; PNC is p-nitro phenyl chloroformate; py: pyridine compound
Scheme 1
Wherein the modified gelatin polysaccharide of the second component
Figure 173607DEST_PATH_IMAGE002
The preparation method of (a) is shown in the following scheme 2:
the method specifically comprises the following steps: dissolving 1 equivalent of poloxamer and 1.5 equivalent of p-nitrophenyl chloroformate in pyridine for reaction at normal temperature, purifying, and heating the obtained product and an appropriate amount of gelatin polysaccharide in pyridine to 90 ℃ for reaction to obtain the compound
Figure 8183DEST_PATH_IMAGE002
The gelatin polysaccharide of the second component.
Figure 574294DEST_PATH_IMAGE004
Wherein PNC is p-nitro phenyl chloroformate; py: pyridine compound
Scheme 2
Drawings
Fig. 1 is a schematic view of the rapid surgical adhesive sealant of the present invention.
Detailed Description
As shown in fig. 1, in the rapid surgical adhesive sealant 100 provided by the present invention, there are included: a first component solid powder 11 loaded in a first container 10, a second component solution 21 loaded in a second container 20, and an application bar 30 for mixing gel solution precursors and applying the gel directly to a surgical site.
A solid powder component (first component) 11 selected from multi-armed polyethylene glycol (multi-arm PEG-SG) with bis glutarate-hydroxysuccinimide ester modification in a tray in a closed first container 10. The multi-arm polyethylene glycol is double-arm polyethylene glycol, four-arm polyethylene glycol or eight-arm polyethylene glycol (2-arm PEG-SG, 4-arm PEG-SG or 8-arm PEG-SG), preferably four-arm polyethylene glycol and eight-arm polyethylene glycol. In addition, a proper amount of FD & C Blue 1 Blue medical dye can be added into the powder to increase the visibility, so that the application is convenient;
a solution component (second component) 21 in a closed second container 20 syringe or plastic tubing, the solute of the solution component being selected from the group consisting of modified gelatin polysaccharides. The solvent of the solution is phosphate or borate buffered solution with pH4 to 12.
The adhesive sealant also includes a dauber 30 for dissolving, mixing the first component solids and applying the pre-gel solution.
The components constitute the formulation of the gel coating kit, based on the total weight of the formulation. The weight percentage of the PEG compound is 5-20%, preferably 7-15%, and most preferably 9%; the weight percentage of the gelatin polysaccharide compound is 0.2-3%, preferably 0.5-2%, and most preferably 1%. And, when the two components are mixed, the sealant hydrogel can be rapidly and firmly applied to a surgical site.
The gel coating kit can also be added with hemostatic drugs, antibiotic drugs, antiviral drugs and particularly compound drugs which are combined, and the weight percentage of the drugs added can be 0.01-25 percent based on the total weight of the formula.
The hemostatic medicine can be selected from tranexamic acid and thrombin; the antibiotic medicines which can be added can be selected from penicillin, chloramphenicol, tobramycin, gentamicin, amikacin and polymyxin; the antiviral drug which can be added can be selected from ribavirin, ganciclovir and acyclovir.
The specific use method is as follows:
unpacking the outer wrap of the rapid surgical adhesive sealant 100 and the first container 10 tray; extruding/injecting the second component solution 21 in the second container into the tray of the first container 10; gently stirring the liquid in 10 with the tail end of the applicator wand 30 to rapidly dissolve the first component 11 solids; dipping an appropriate amount of the mixed solution (gel precursor) from the tray of the first container 10 with the tip of the application stick 30 and applying it to the site of action gently; finally, a short time (between a few seconds and a few tens of seconds) is waited to form the hydrogel sealing adhesive with good tissue adhesion.
The following specific examples are set forth below to further illustrate the invention:
in the following examples and comparative examples, the properties of the sealant for rapid surgical adhesion were measured as follows:
the gelling time test method comprises the following steps: the surgical adhesive sealant kit was opened, the first component solid powder was fully dissolved using the second component solution and the mixed solution was added dropwise into a 37 ℃ vial until the rotating vial did not flow, and the time was recorded as gel-forming time (rotating vial method).
Degradation time test method: the surgical adhesive sealant kit was opened, the first component solid powder was dissolved thoroughly with the second component solution, and after gel formation the hydrogel was placed in a simulated physiological environment (i.e., 37 ℃ PBS solution) and the degradation time was recorded.
Bond strength test method: the surgical adhesive sealant kit was opened, the first component solid powder was thoroughly dissolved and spread onto the pigskin substrate using the second component solution, and the tissue adhesive bonding performance test method was followed as part 1 of YY/T0729.1: lap-shear tensile load strength was tested.
Cytotoxicity test methods: the surgical adhesive sealant kit was opened and the first component solid powder was thoroughly dissolved using the second component solution and placed on cell culture media and tested according to the method specified in GB/T16886.5.
The advantageous effects of the present invention will be more fully illustrated by the following examples.
Example 1 with 0.29g of p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 10g of PEG with the molecular weight of 10000 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 12 is prepared into a second component solution. And 2-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 3: 79. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 36 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 33 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate to obtain a set of sealant I, wherein the bonding strength is 87N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 2
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 1g of PEG with the molecular weight of 1000 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 4 is prepared into a second component solution. And 2-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 0.2: 79.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using the second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 30 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 37 days; taking a set of sealant firstly, fully dissolving the first component solid powder by using a second component solution, and smearing the first component solid powder on a pigskin substrate, wherein the bonding strength is 91N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 3
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 6g of PEG with the molecular weight of 6000 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 8 is prepared into a second component solution. And 2-arm SG-PEG dry powder with the single-arm molecular weight of 8000 is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 2: 83. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly kit, fully dissolving the first component solid powder by using the second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 27 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 39 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate, wherein the bonding strength is measured to be 95N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 4
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 3g of PEG with the molecular weight of 3000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 6 is prepared into a second component solution. And 2-arm SG-PEG dry powder with the single-arm molecular weight of 8000 is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 0.5: 84.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 2336 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 43 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 101N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 5
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 5g of PEG with the molecular weight of 5000 and 3g of gelatin with the molecular weight of 3000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 7.4 is prepared into a second component solution. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (5000) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 9: 1: 90. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 19 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 47 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 115N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 6
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 6g of PEG with the molecular weight of 6000 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 8 is prepared into a second component solution. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (2000) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 2: 91. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 22 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 44 days; taking a set of sealant (i) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 105N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 7
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 3g of PEG with the molecular weight of 3000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 6 is prepared into a second component solution. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (2000) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 0.5: 92.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 25 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 393 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate, wherein the bonding strength is 97N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 8
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 10g of PEG with the molecular weight of 10000 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 12 is prepared into a second component solution. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (800) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 3: 92. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 28 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 33 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 93N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 9
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 1g of PEG with the molecular weight of 1000 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 4 is prepared into a second component solution. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (800) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 0.2: 94.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 33 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 29 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate to obtain a sealant I with the bonding strength of 85N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 10
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 10g of PEG with the molecular weight of 10000 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 12 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with single-arm molecular weight (10000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 3: 79. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 35 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 34 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 96N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 11
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 1g of PEG with the molecular weight of 1000 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 4 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with single-arm molecular weight (10000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 0.2: 79.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using the second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 31 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 36 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 102N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 12
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 6g of PEG with the molecular weight of 6000 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 8 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of 8000, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 2: 83. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 28 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 40 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 107N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 13
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 3g of PEG with the molecular weight of 3000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 6 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of 8000, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 0.5: 84.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 22 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 44 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 110N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 14
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 5g of PEG with the molecular weight of 5000 and 3g of gelatin with the molecular weight of 3000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 7.4 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (5000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 9: 1: 90. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 20 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 49 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 123N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 15
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 6g of PEG with the molecular weight of 6000 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 8 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (2000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 2: 91. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 22 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 47 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 117N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 16
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 3g of PEG with the molecular weight of 3000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 6 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (2000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 0.5: 92.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly kit, fully dissolving the first component solid powder by using the second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 27 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 38 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 106N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 17
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 10g of PEG with the molecular weight of 10000 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 12 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (800), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 3: 92. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 29 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 35 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 101N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 18
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 1g of PEG with the molecular weight of 1000 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 4 is prepared into a second component solution. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (800), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 0.2: 94.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using the second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 31 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 30 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 93N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 19
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 10g of PEG with the molecular weight of 10000 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 12 is prepared into a second component solution. And 8-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 3: 79. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly kit, fully dissolving the first component solid powder by using the second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 37 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 36 days; taking a set of sealant (i) and using a second component solution to fully dissolve the first component solid powder and smearing the first component solid powder on a porcine eye cornea substrate, and measuring the bonding strength of the first component solid powder to be 105N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 20
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 1g of PEG with the molecular weight of 1000 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 4 is prepared into a second component solution. And 8-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 0.2: 79.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 33 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 39 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 111N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 21
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 6g of PEG with the molecular weight of 6000 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 8 is prepared into a second component solution. And 8-arm SG-PEG dry powder with the single-arm molecular weight of 8000 is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 2: 83. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 29 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 41 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 118N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 22
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 3g of PEG with the molecular weight of 3000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 6 is prepared into a second component solution. And 8-arm SG-PEG dry powder with the single-arm molecular weight of 8000 is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 0.5: 84.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 24 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 46 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 123N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 23
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 5g of PEG with the molecular weight of 5000 and 3g of gelatin with the molecular weight of 3000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 7.4 is prepared into a second component solution. And 8-arm SG-PEG dry powder with the single-arm molecular weight of (5000) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 9: 1: 90. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 20 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 50 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 135N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 24
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 6g of PEG with the molecular weight of 6000 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 8 is prepared into a second component solution. And preparing a first component from 8-arm SG-PEG dry powder with the single-arm molecular weight of (2000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 2: 91. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 22 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 48 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 126N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 25
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 3g of PEG with the molecular weight of 3000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 6 is prepared into a second component solution. And preparing a first component from 8-arm SG-PEG dry powder with the single-arm molecular weight of (2000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 0.5: 92.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly, sleeving the assembly, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 26 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 39 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 115N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 26
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 10g of PEG with the molecular weight of 10000 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 12 is prepared into a second component solution. And preparing a first component from 8-arm SG-PEG dry powder with the single-arm molecular weight of (800), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 3: 92. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly kit, fully dissolving the first component solid powder by using the second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 27 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 37 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate to obtain the bonding strength of 113N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 27
At 0.29g p-toluenesulfonyl chloride (TsCl); 0.2g of p-nitrophenylchloroformate (PNC); 0.39g cholesterol; 1g of PEG with the molecular weight of 1000 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the scheme one to prepare the modified gelatin polysaccharide I of the second component of the fast surgical operation adhesive sealant component set, namely the cholesterol modified gelatin polysaccharide I with the PEG chain, and Phosphate Buffer Solution (PBS) with the pH value of 4 is prepared into a second component solution. And preparing a first component from 8-arm SG-PEG dry powder with the single-arm molecular weight of (800), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 0.2: 94.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Taking a set of the quick surgical operation adhesive sealant assembly kit, fully dissolving the first component solid powder by using the second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 32 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 33 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 101N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Table one: example data sheet of sealant (1)
Practice of Example (b) Multi-arm PEG Number of arms Multi-arm PEG single arm Molecular weight Multi-arm PEG compositions containing Amount (%) Gelatin polysaccharide Molecular weight For modifying gelatin Molecular weight of PEG Gelatin polysaccharide content Amount (%) Buffer solution pH value When gelling Workshop(s) Strong adhesion Degree (N) Time of decomposition (day)
1 2 10000 20 5000 10000 3 12 36 87 33
2 2 10000 20 1000 1000 0.2 4 30 91 37
3 2 8000 15 3500 6000 2 8 27 95 39
4 2 8000 15 2000 3000 0.5 6 23 101 43
5 2 5000 9 3000 5000 1 7.4 19 115 47
6 2 2000 7 3500 6000 2 8 22 105 44
7 2 2000 7 2000 3000 0.5 6 25 97 39
8 2 800 5 5000 10000 3 12 28 93 33
9 2 800 5 1000 1000 0.2 4 33 85 29
10 4 10000 20 5000 10000 3 12 35 96 34
11 4 10000 20 1000 1000 0.2 4 31 102 36
12 4 8000 15 3500 6000 2 8 28 107 40
13 4 8000 15 2000 3000 0.5 6 22 110 44
14 4 5000 9 3000 5000 1 7.4 20 123 49
15 4 2000 7 3500 6000 2 8 22 117 47
16 4 2000 7 2000 3000 0.5 6 27 106 38
17 4 800 5 5000 10000 3 12 29 101 35
18 4 800 5 1000 1000 0.2 4 31 93 30
19 8 10000 20 5000 10000 3 12 37 105 36
20 8 10000 20 1000 1000 0.2 4 33 111 39
21 8 8000 15 3500 6000 2 8 29 118 41
22 8 8000 15 2000 3000 0.5 6 24 123 46
23 8 5000 9 3000 5000 1 7.4 20 135 50
24 8 2000 7 3500 6000 2 8 22 126 48
25 8 2000 7 2000 3000 0.5 6 26 115 39
26 8 800 5 5000 10000 3 12 27 113 37
27 8 800 5 1000 1000 0.2 4 32 101 33
Example 28
0.2g of p-nitrophenylchloroformate (PNC); 9.8g of poloxamer with the molecular weight of 9840 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 12. And 2-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 3: 79. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 28 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 27 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate to obtain the bonding strength of 77N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 29
0.2g of p-nitrophenylchloroformate (PNC); and (3) 98.8g of poloxamer with the molecular weight of 8830 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the rapid surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of the poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 4. And 2-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 0.2: 79.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 23 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 33 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 82N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 30
0.2g of p-nitrophenylchloroformate (PNC); 9.68g of poloxamer with the molecular weight of 9600 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 8. And 2-arm SG-PEG dry powder with the single-arm molecular weight of 8000 is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 2: 83. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 20 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 35 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 84N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 31
0.2g of p-nitrophenylchloroformate (PNC); 9g of poloxamer with the molecular weight of 9000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide of poloxamer is prepared into a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 6. And 2-arm SG-PEG dry powder with the single-arm molecular weight of 8000 is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 0.5: 84.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 14 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 39 days; taking a set of sealant firstly, fully dissolving the first component solid powder by using a second component solution, and smearing the first component solid powder on a pigskin substrate, wherein the bonding strength is 91N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 32
0.2g of p-nitrophenylchloroformate (PNC); 9.3g of poloxamer with the molecular weight of 9300 and 3g of gelatin with the molecular weight of 3000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 7.4. And 2-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 9: 1: 90. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 12 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 43 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on the pigskin substrate, and measuring the bonding strength of the first component solid powder to be 103N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 33
0.2g of p-nitrophenylchloroformate (PNC); 9.6g of poloxamer with the molecular weight of 9600 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 8. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (2000) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 2: 91. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 15 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 38 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate, wherein the bonding strength is 97N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 34
0.2g of p-nitrophenylchloroformate (PNC); 9g of poloxamer with the molecular weight of 9000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide of poloxamer is prepared into a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 6. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (2000) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 0.5: 92.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 18 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 34 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate to obtain the adhesive strength of 86N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 35
0.2g of p-nitrophenylchloroformate (PNC); 9.8g of poloxamer with the molecular weight of 9840 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 12. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (800) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 3: 92. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 21 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 27 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 82N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 36
0.2g of p-nitrophenylchloroformate (PNC); 8.8g of poloxamer with the molecular weight of 8830 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 4. And 2-arm SG-PEG dry powder with the single-arm molecular weight of (800) is used for preparing a first component, wherein the mass ratio of each component is that multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 0.2: 94.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 26 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 25 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate, wherein the bonding strength is measured to be 73N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 37
0.2g of p-nitrophenylchloroformate (PNC); 9.8g of poloxamer with the molecular weight of 9840 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 12. And preparing a first component from 4-arm SG-PEG dry powder with single-arm molecular weight (10000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 3: 79. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 29 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 30 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 84N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 38
0.2g of p-nitrophenylchloroformate (PNC); and (3) 98.8g of poloxamer with the molecular weight of 8830 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the rapid surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of the poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 4. And preparing a first component from 4-arm SG-PEG dry powder with single-arm molecular weight (10000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 0.2: 79.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 24 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 32 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on the pigskin substrate, and measuring the bonding strength of the first component solid powder to be 94N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 39
0.2g of p-nitrophenylchloroformate (PNC); 9.68g of poloxamer with the molecular weight of 9600 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 8. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of 8000, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 2: 83. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 20 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 36 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 98N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 40
0.2g of p-nitrophenylchloroformate (PNC); 9g of poloxamer with the molecular weight of 9000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide of poloxamer is prepared into a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 6. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of 8000, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 0.5: 84.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 15 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 40 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 102N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
EXAMPLE 41
0.2g of p-nitrophenylchloroformate (PNC); 9.3g of poloxamer with the molecular weight of 9300 and 3g of gelatin with the molecular weight of 3000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 7.4. And preparing a first component from 4-arm SG-PEG dry powder with single-arm molecular weight (10000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 9: 1: 90. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 11 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 45 days; taking a set of sealant I, fully dissolving the first component solid powder by using a second component solution, and coating the first component solid powder on a pigskin substrate to obtain the bonding strength of 113N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 42
0.2g of p-nitrophenylchloroformate (PNC); 9.6g of poloxamer with the molecular weight of 9600 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 8. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (2000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 2: 91. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 16 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 42 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 106N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 43
0.2g of p-nitrophenylchloroformate (PNC); 9g of poloxamer with the molecular weight of 9000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide of poloxamer is prepared into a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 6. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (2000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 0.5: 92.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 19 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 34 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on the pigskin substrate, and measuring the bonding strength of the first component solid powder to be 94N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 44
0.2g of p-nitrophenylchloroformate (PNC); 9.8g of poloxamer with the molecular weight of 9840 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 12. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (800), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 3: 92. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 23 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 30 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 90N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 45
0.2g of p-nitrophenylchloroformate (PNC); 8.8g of poloxamer with the molecular weight of 8830 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 4. And preparing a first component from 4-arm SG-PEG dry powder with the single-arm molecular weight of (800), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 0.2: 94.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 24 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 26 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 84N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 46
0.2g of p-nitrophenylchloroformate (PNC); 9.8g of poloxamer with the molecular weight of 9840 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 12. And 8-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 3: 79. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 30 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 32 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 93N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 47
0.2g of p-nitrophenylchloroformate (PNC); and (3) 98.8g of poloxamer with the molecular weight of 8830 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the rapid surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of the poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 4. And 8-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 20: 0.2: 79.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 25 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 33 days; taking a set of sealant firstly, fully dissolving the first component solid powder by using a second component solution, and smearing the first component solid powder on a pigskin substrate, wherein the bonding strength is 99N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 48
0.2g of p-nitrophenylchloroformate (PNC); 9.68g of poloxamer with the molecular weight of 9600 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 8. And 8-arm SG-PEG dry powder with the single-arm molecular weight of 8000 is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 2: 83. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 20 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 36 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 110N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 49
0.2g of p-nitrophenylchloroformate (PNC); 9g of poloxamer with the molecular weight of 9000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide of poloxamer is prepared into a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 6. And 8-arm SG-PEG dry powder with the single-arm molecular weight of 8000 is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 15: 0.5: 84.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 15 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 42 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 115N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 50
0.2g of p-nitrophenylchloroformate (PNC); 9.3g of poloxamer with the molecular weight of 9300 and 3g of gelatin with the molecular weight of 3000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 7.4. And 8-arm SG-PEG dry powder with single-arm molecular weight (10000) is used for preparing a first component, wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 9: 1: 90. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 13 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 45 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on the pigskin substrate, and measuring the bonding strength of the first component solid powder to be 128N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 51
0.2g of p-nitrophenylchloroformate (PNC); 9.6g of poloxamer with the molecular weight of 9600 and 3.5g of gelatin with the molecular weight of 3500 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 8. And preparing a first component from 8-arm SG-PEG dry powder with the single-arm molecular weight of (2000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 2: 91. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 14 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time to be 42 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 116N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 52
0.2g of p-nitrophenylchloroformate (PNC); 9g of poloxamer with the molecular weight of 9000 and 2g of gelatin with the molecular weight of 2000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide of poloxamer is prepared into a second component solution by Phosphate Buffered Saline (PBS) with the pH value of 6. And preparing a first component from 8-arm SG-PEG dry powder with the single-arm molecular weight of (2000), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 7: 0.5: 92.5. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 19 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 35 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 106N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 53
0.2g of p-nitrophenylchloroformate (PNC); 9.8g of poloxamer with the molecular weight of 9840 and 5g of gelatin with the molecular weight of 5000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 12. And preparing a first component from 8-arm SG-PEG dry powder with the single-arm molecular weight of (800), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 3: 92. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 22 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 33 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 101N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Example 54
0.2g of p-nitrophenylchloroformate (PNC); 8.8g of poloxamer with the molecular weight of 8830 and 1g of gelatin with the molecular weight of 1000 are synthesized by the method of the second scheme to prepare the modified gelatin polysaccharide (II) of the second component of the fast surgical adhesive sealant component set, namely the modified gelatin polysaccharide (II) of poloxamer is used for preparing a solution of the second component by Phosphate Buffered Saline (PBS) with the pH value of 4. And preparing a first component from 8-arm SG-PEG dry powder with the single-arm molecular weight of (800), wherein the mass ratio of each component is multi-arm PEG: modified gelatin polysaccharide: PBS = 5: 0.2: 94.8. thereby obtaining a rapid surgical adhesive sealant assembly kit. Sleeving a set of rapid surgical operation bonding sealant components, fully dissolving the first component solid powder by using a second component solution, dropwise adding the mixed solution into a small bottle at 37 ℃, and measuring the gelling time to be 26 s; taking a set of sealant I component, fully dissolving the first component solid powder by using a second component solution, placing hydrogel in a simulated physiological environment (namely PBS solution at 37 ℃) after the gel is formed, and measuring the degradation time of the hydrogel to be 28 days; taking a set of sealant (I) and using a second component solution to fully dissolve the first component solid powder and coating the first component solid powder on a pigskin substrate, and measuring the bonding strength of the first component solid powder to be 93N; and no cytotoxicity is found in cell tests, so that the clinical medical requirements are met.
Table two: example data sheet of sealant-
Fruit of Chinese wolfberry Applying (a) to Example (b) Multi-arm PEG arm Number of Multi-arm PEG single Arm partQuantum of Multi-arm PEG Content (%) Gelatin polypeptide Sugar molecules Measurement of For modifying gelatin Poloxamer molecular weight Gelatin polypeptide Sugar content (%) Buffer solution pH value of the liquid Gelatinizing Time (s) Bonding Strength of (N) At the time of decomposition Workshop (day)
28 2 10000 20 5000 9840 3 12 28 77 27
29 2 10000 20 1000 8830 0.2 4 23 82 33
30 2 8000 15 3500 9600 2 8 20 84 35
31 2 8000 15 2000 9000 0.5 6 14 91 39
32 2 5000 9 3000 9300 1 7.4 12 103 43
33 2 2000 7 3500 9600 2 8 15 97 38
34 2 2000 7 2000 9300 0.5 6 18 86 34
35 2 800 5 5000 9840 3 12 21 82 27
36 2 800 5 1000 8830 0.2 4 26 73 25
37 4 10000 20 5000 9840 3 12 29 84 30
38 4 10000 20 1000 8830 0.2 4 24 94 32
39 4 8000 15 3500 9600 2 8 20 98 36
40 4 8000 15 2000 3000 0.5 6 15 102 40
41 4 5000 9 3000 9300 1 7.4 11 113 45
42 4 2000 7 3500 9600 2 8 16 106 42
43 4 2000 7 2000 9000 0.5 6 19 94 34
44 4 800 5 5000 9840 3 12 23 90 30
45 4 800 5 1000 8830 0.2 4 24 84 26
46 8 10000 20 5000 9840 3 12 30 93 32
47 8 10000 20 1000 8830 0.2 4 25 99 33
48 8 8000 15 3500 9600 2 8 20 110 36
49 8 8000 15 2000 9000 0.5 6 15 115 42
50 8 5000 9 3000 9300 1 7.4 13 128 45
51 8 2000 7 3500 9600 2 8 14 116 42
52 8 2000 7 2000 9000 0.5 6 19 106 35
53 8 800 5 5000 9840 3 12 22 101 33
54 8 800 5 1000 8830 0.2 4 26 93 28
Comparative example 1
0.9g of 8-arm PEG dry powder with single-arm molecular weight of 800 is selected as a first component; a second component solution prepared from 0.02g of trilysine and a phosphate buffer solution with a pH of 7.4. The mass ratio of the PEG: a trilysine: phosphate buffer = 9: 0.2: 90.8. the performance of the sealing adhesive and clinical research show that: the sealing adhesive has the gelling time of 14s, the adhesive strength of 63N, the flexibility meeting the requirement, no cytotoxicity is found, and the sealing adhesive can be thoroughly decomposed after 2 days to meet the clinical medical requirement.
Comparative example 2
0.9g of 8-arm PEG dry powder with single-arm molecular weight of 5000 is selected as a first component; a second component solution prepared from 0.1g of trilysine and a phosphate buffer solution with a pH of 7.4. The mass ratio of the PEG: a trilysine: phosphate buffer = 9: 1: 90. the performance of the sealing adhesive and clinical research show that: the sealing adhesive has the gelling time of 8s, the adhesive strength of 77N, the flexibility meeting the requirement, no cytotoxicity is found, and the sealing adhesive can be completely decomposed after 4 days to meet the clinical medical requirement.
Comparative example 3
2g of 8-arm PEG dry powder with single-arm molecular weight of 10000 is selected as a first component; a second component solution prepared from 0.3g of trilysine and a phosphate buffer solution with a pH of 12. The mass ratio of the PEG: a trilysine: phosphate buffer = 20: 3: 77. the performance of the sealing adhesive and clinical research show that: the sealing adhesive has the gelling time of 15s, the adhesive strength of 65N, the flexibility meeting the requirement, no cytotoxicity is found, and the sealing adhesive can be completely decomposed after 3 days to meet the clinical medical requirement.
Tests show that the effect of each example is better than that of a comparative example, wherein the gelling time of the comparative example is too short, so that the sealant is not favorably mixed and used; and if the time is too long, the use effect is influenced, and the difficulty is increased for the operation. Repeatedly verifying that the gelling time is controlled within 5-50 s, wherein 10-30 s is preferred, and the optimal time is 13s, so that the first part and the second part of the sealant can be fully mixed and can be immediately applied to the operation part; in addition, the bonding strength of each embodiment is higher than that of the comparative example, so that the sealing use after operation is more facilitated; finally, the decomposition time of the embodiment is enough to support the postoperative wound healing, according to the general rule of the patient after the operation, the postoperative wound healing generally needs about 25 days, but the wound healing time of part of the patients is longer due to individual difference, for the case, the longer the decomposition time is, the better the decomposition time is, the enough to support the operation wound healing, but the comparative example is much less effective.
The above description is only a part of the embodiments of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that are not conceived by the inventive work should be included within the scope of the present invention. Therefore, the protection scope of the present invention should be determined by the protection scope defined in the claims.

Claims (14)

1. A kit of rapid surgical adhesive sealant assemblies comprising:
a) a first component in a closed first container, the first component being a solid powder component selected from multi-armed polyethylene glycol with bis-glutarate-hydroxysuccinimide ester modification selected from two-armed polyethylene glycol, four-armed polyethylene glycol, or eight-armed polyethylene glycol,
b) a second component in a closed second container, the second component being a solution component having a solute selected from the group consisting of modified gelatin polysaccharide and a solvent for the solution component being a biological buffer solution;
c) the kit further comprises an applicator for mixing the first and second components and the solution prior to application of the gel;
wherein the content of the first and second substances,
the first component and the second component jointly form a formula of the rapid surgical operation bonding sealant component set, and the weight percentage of the multi-arm polyethylene glycol modified by the bis-glutarate-hydroxysuccinimide ester is 7-15 percent based on the total weight of the formula; the weight percentage of the modified gelatin polysaccharide is 0.5-2%; the weight percentage of the biological buffer solution is 83-92.5 percent;
wherein the modified gelatin polysaccharide in the solution components is selected from the following 2 modified gelatin polysaccharides: firstly, cholesterol modified gelatin polysaccharide with PEG chain, or secondly, gelatin polysaccharide modified by poloxamer;
and wherein the weight average molecular weight of the modified gelatin polysaccharide before modification is 2000-3500.
2. The rapid surgical adhesive sealant assembly kit of claim 1, wherein the weight percent of the multi-arm polyethylene glycol with bis-glutarate-hydroxysuccinimide ester modification is 9%, the weight percent of the modified gelatin polysaccharide is 1%, the weight percent of the biological buffer solution is 90%, and the weight average molecular weight of the modified gelatin polysaccharide before modification is 3000 based on the total weight of the formulation.
3. The kit of rapid surgical adhesive sealant assemblies as recited in claim 1, wherein the first container is a tray and/or the second container is a hose or syringe.
4. The kit of rapid surgical adhesive sealant assemblies as recited in claim 1, wherein the biological buffer solution is selected from phosphate or borate buffer solutions.
5. The kit of rapid surgical adhesive sealant assemblies as recited in claim 4, wherein the buffer solution has a pH of 6 to 8.
6. The kit of rapid surgical adhesive sealant assemblies as recited in claim 5, wherein said buffer solution has a pH of 7.4.
7. The kit of rapid surgical adhesive sealant components as recited in claim 1, wherein the PEG molecular weight of the modified gelatin polysaccharide (i) is 3000 to 6000 and the poloxamer molecular weight of the modified gelatin polysaccharide (i) is 9000 to 9600.
8. The kit of rapid surgical adhesive sealant components as recited in claim 7, wherein the PEG molecular weight for the modified gelatin polysaccharide (i) is 5000 and the poloxamer molecular weight for the modified gelatin polysaccharide (ii) is 9300.
9. The rapid surgical adhesive sealant assembly kit of claim 1, wherein the single arm weight average molecular weight of the multi-arm PEG of the first component is 2000 to 8000.
10. The kit of rapid surgical adhesive sealant assemblies as recited in claim 9, wherein the single arm weight average molecular weight of the multi-arm PEG of the first component is 5000.
11. The rapid surgical adhesive sealant kit of claim 1, wherein the first or second component of the rapid surgical adhesive sealant kit further comprises a hemostatic drug, an antibiotic drug, an antiviral drug, or a combination thereof.
12. The kit of rapid surgical adhesive sealant assemblies as recited in claim 1, wherein said first component solid powder further includes a medical grade dye to increase the operability of the sealant application.
13. The kit of rapid surgical adhesive sealant components of claim 12, wherein the medical dye included in the first component solid powder is selected from FD & C Blue #1 Blue dye.
14. The rapid surgical adhesive sealant assembly set of claim 1, wherein the dauber is a medical cotton swab or foamed polyethylene, wherein one end of the dauber is used for mixing and stirring two precursor solutions; the other end is responsible for smearing the evenly mixed solution to the operation position so as to form gel at the operation position and achieve the sealing effect.
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