CN108159483A - Rapid surgical binds sealant - Google Patents

Rapid surgical binds sealant Download PDF

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Publication number
CN108159483A
CN108159483A CN201810115515.4A CN201810115515A CN108159483A CN 108159483 A CN108159483 A CN 108159483A CN 201810115515 A CN201810115515 A CN 201810115515A CN 108159483 A CN108159483 A CN 108159483A
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China
Prior art keywords
component
sealant
suit
solution
gelatin
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CN201810115515.4A
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CN108159483B (en
Inventor
马军
李储忠
甘少磊
王秀梅
高阳
白云昊
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Jiangxi Bo'en Ruier Biotechnology Co Ltd
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Jiangxi Bo'en Ruier Biotechnology Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0031—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/08—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/104—Gelatin

Abstract

Rapid surgical bonding sealant is a kind of bi-component in-situ hydrogel sealant for being intended to surgical site infections prevention operative site and leakage and infection occurring.It includes：In the first container（Closed pallet）In the multi-arm polyethylene glycol with double glutarate hydroxysuccinimide eaters modifications（multi‑arm PEG‑SG）Powder（First component）；In second container（The plastics sebific duct or syringe of sealing）In modified gelatin solution（Second component）；An and medical paint daubs（Medical cotton stick or polyethylene foamed）.During use, it is first turned on second container, second component solution is squeezed/injected in the first container pallet, and it is quickly stirred using paint daubs tail end, after being completely dissolved the first component powders, sealant coating will be binded to operative site by paint daubs head end, firm hydrogel sealant can be formed by hanging on.

Description

Rapid surgical binds sealant
Technical field
The present invention relates to adhesive of medical more particularly to a kind of polyethylene glycol（PEG）Hydrogel adhesive of medical.
Background technology
Compared to traditional operation stitching closed system（Such as：Suture, hemostatic gauze, styptic sponge, polysaccharide styptic powder Deng）, in-situ hydrogel sealer gradually shows one's talent when with many merits, has been to be concerned by more and more people.
First, in-situ hydrogel is sealed binder and is deposited in the form of the Liquid precursor without fixed shape before gel is formed It is being directly acted at action site by simply injecting or applying.Delivering mode is simple and fast and easily operated, and its The characteristic of unique amorphous liquid precursor also give its can more preferable contact action site ability, make itself and action site Stick more securely.Therefore, the agent of in-situ hydrogel adhesive can't be as traditional bio-medical sutures sealing material It is limited to the irregular shape in material effects site and greatly limits the use of traditional material and reduce its using effect；
Secondly, in-situ hydrogel closing binder can be in very short a period of time after action site is reached in the form of Liquid precursor （Usually in minutes）Inside quickly form the figurate hydrogel solid of tool.It will not be brought in the process for human body Major injury and product is non-toxic to humans；
Moreover, the composition of solid hydrogel that in-situ hydrogel closing binder is formed after action site is applied to is most of All it is water, and the macromolecular for forming hydrogel backbone is the good hydrophilic molecule of biocompatibility, so, the water-setting of formation Glue has the microenvironment very similar with the matrix of cell growth.Therefore the growth of cell is very suitable for, sealer is acted on The recovery and healing in site all have very positive meaning；
In addition, special construction possessed by the solid hydrogel formed by in-situ hydrogel closing binder also gives it These components can be made directly to reach action site without to body with components such as load cells, the factor, nutriment and drugs Other tissues have an impact, and will not cause to waste.Also, the special reticular structure of hydrogel can not only effectively lock water Molecule, while the small molecules such as the factor, nutriment, drug can be also lockked, so as to be also played to these micromolecular compounds Certain slow releasing function；
Moreover, a part of hydrogel closing binder materials due to its intrinsic constituent so that materials combine is certain Antibacterial ability.Such as some aquagels and a part of polypeptide hydrogel are just due to its molecular characterization so that material performance Very excellent antibacterial characteristics are gone out, so as to which the action site to hydrogel closing binder plays the role of antimicrobial antiphlogistic；
Finally, it has to be mentioned that：In-situ hydrogel closes binder after action site forms solid hydrogel, in anti-stop bit While point occurs leakage, promotes tissue repair, hydrogel restores also with the healing of site organization and gradually decomposes.And After tissue healing completely, hydrogel can decompose completely, and decomposition product is non-toxic to humans.Finally, decomposition product can It is external to be completely exhausted out, and harmful effect is not caused to body.
And for in-situ hydrogel, we can be divided into two major class by the plastic mechanism difference of its Hydrogel Component： Physics in-situ hydrogel and chemical in situ hydrogel.Both in-situ hydrogels can quickly form after action site is reached Solid hydrogel, but all because respectively have different advantages with it is insufficient due to limit its application, simply introduce lower two kinds below The characteristics of in-situ hydrogel.
Physical hydrogel in situ is to experience extraneous physics letter after hydrogel precursor reaches action site in liquid form Number（Such as：Temperature, pH value, ion etc.）Stimulation, thus rapidly closing hydrogel formed in situ（Such as：It is modified with PIN-PAM Biomolecule can form hydrogel in 37 DEG C or so of human body temperature；Some polypeptides with particular sequence are then in condition of neutral pH It is tangled by the mutual attractive force of positive and negative charge to generate down, forms in-situ hydrogel；Sodium alginate aqueous solution is encountering Ca2+Afterwards It can chelate, so as to form physics in-situ hydrogel）.These physical hydrogels can be formed within the very short time, And some high temperature can't be generated during plastic, peracid, cross the stimulations unfavorable to human body such as alkali, will not be generated pair Toxic, the harmful substance of human body.But then, physical hydrogel in situ is relatively weak as other physical hydrogels Mechanical performance and its application of relatively weak tissue energy of adhesion power limit and development.Because the molding of physical hydrogel is mainly By physical action（Such as electrostatic force, hydrophobic force, hydrogen bond）, so, aquogel system is more easily damaged, this results in its mechanicalness Can be poor, easily from tissue loss, and very easily decompose, therefore limit the development of physical hydrogel sealant in situ.
In-situ chemical hydrogel is after action site is reached in the form of Liquid precursor, and chemistry occurs at action site Reaction（Such as：The addition reaction that liquid is mixed and occurred；" click chemistry " annulation that azido group occurs with acetylene bond；And Light-initiated addition reaction）, and quickly form chemical water gel solids.Because the composition of its hydrogel is participated in by chemical reaction , thus generally have good mechanical performance, also, compared to physics in-situ hydrogel for, chemical in situ hydrogel is more Add and be not easy to be decomposed, its effectiveness can be made thoroughly to play without decomposing halfway.For but then, chemical in situ hydrogel There is also the deficiencies of itself：First, the chemical reaction occurred during plastic may be along with the play of temperature, pH value etc. Strong variation generates action site certain injury；Secondly, some catalysis toxic to human body are likely to require during plastic Agent；In addition, the chemical reaction during plastic is also possible to have some harmful by-products；Finally, due to it is most The hydrogel formed afterwards has good mechanical performance, leads to its not malleable shape after plastic.These all limit chemistry The development and application of in-situ hydrogel sealer.
It is a kind of new for being applied after surgical clinical operation it is an object of the invention to overcome the deficiencies of the prior art and provide In wound location, to reach rapid closing wound and prevent the disposable gel seal binder leaked, also, this is glutinous Mixture can be shaped to firm gel rapidly at wound, which shows extremely strong tissue Adhering capacity.Described Gel used in binder has good biological degradability, biocompatibility and security reliability.
Invention content
In order to complete above-mentioned goal of the invention, the present invention provides a kind of rapid surgical bonding sealant suit, Including：
a）The first component in the first container of closing, first component be solid powder components, the solid powder group The multi-arm polyethylene glycol with double glutarates-hydroxysuccinimide eater modification is selected from, the multi-arm polyethylene glycol is selected from Both arms polyethylene glycol, four arm polyethylene glycol or eight arm polyethylene glycol are preferably selected from four arm polyethylene glycol or eight arm polyethylene glycol,
b）The second component in the second container of closing, second component be solution component, the solute of the solution component Solvent selected from modified gelatin polysaccharide and the solution component is biological buffer solutions；
c）The component suit is also comprising dauber, for molten before the first component of mixing and the second component and smearing gel Liquid；
Wherein,
First and second components collectively form the formula of the rapid surgical bonding sealant suit, with the formula Total weight, the weight percent of the multi-arm polyethylene glycol with double glutarates-hydroxyl amber glass imide esters modification It is 5% ~ 20%, preferably 7 ~ 15%, optimal is 9%；The weight percent of the gelatin polysaccharide of the modification is 0.2% ~ 3%, preferably 0.5 ~ 2%, optimal is 1%；The weight percent of the biological buffer solutions is 77% ~ 99.8%, preferably 83% ~ 92.5%, optimal to be 90%.It, can firm sealant hydrogel rapidly coated on operative site also, after two component mixes.
Wherein, the first container is pallet and/or the second container is sebific duct or syringe.
Wherein, the biological buffer solutions are selected from phosphate or borate buffer solution.
Wherein, the pH value of the buffer solution is 4 to 12, preferably 6 ~ 8, and optimal is 7.4.
Wherein, the gelatin polysaccharide of the modification in the second component solution is selected from following 2 kinds modified gelatin polysaccharide：Band The cholesterol modifying gelatin polysaccharide of PEG chains orThe gelatin polysaccharide being modified by poloxamer.
Wherein, the weight average molecular weight before the gelatin of the modification is polysaccharide-modified for 1000 to 5000 dalton, preferably 2000 ~ 3500, optimal is 3000；Modified gelatin polysaccharideIn for modified gelatin polysaccharide PEG molecular weight for 1000 ~ 10000, In preferably 3000 ~ 6000, optimal is 5000, modified gelatin polysaccharideIn be used for modified gelatin polysaccharide poloxamer molecular weight It is 9840 ~ 8830, preferably 9600 ~ 9000, optimal is 9300.
Wherein, the single armed weight average molecular weight of the multi-arm PEG of first component be 800 to 10000 dalton, preferably 2000 ~ 8000, wherein optimal is 5000.
Wherein, the addition hemostasis class in the first component or the second component of rapid surgical bonding sealant suit Drug, antibiotic medicine, antiviral class drug or their combination.With the total weight of above-mentioned formula, the drug is added Weight percent can be 0.01% ~ 25%.
Wherein, suitable medical dyestuff should be added in into the first constituent solid powder can with increase that sealant uses Operability.
Wherein, the medical dyestuff added in the first constituent solid powder is selected from FD ＆ C Blue#1 blue dyes.
Wherein, the dauber is medical cotton stick or polyethylene foamed daubers one end for two kinds of mixing Precursor solution；The other end is responsible for uniformly mixed solution being applied to operative site, to form gel in surgical site, plays Sealing effect.
Wherein, the gelatin polysaccharide of the modification of the second componentPreparation method as shown in following scheme 1：
Specially：Take 1 equivalent cholesterol and 2 equivalent methyl benzene sulfonyl chlorides reacted at room temperature in pyridine after 12h through dichloromethane with Water extraction is evaporated to obtain white solid, and the PEG that white solid is dissolved in pyrido 1 equivalent of addition reacts at room temperature, treats anti- It should terminate to purify.Gained sample with 1.5 equivalents is dissolved in nitro phenyl chloroformate after pyridine through purification with it is a certain amount of Gelatin polysaccharide reacts the gelatin polysaccharide that purification obtains the modification of the second component in DMSO。
Wherein：TsCL:Toluene sulfonyl chloride；PNC:To nitro phenyl chloroformate；Py：Pyridine
Scheme 1
Wherein, the gelatin polysaccharide of the modification of the second componentPreparation method as shown in following scheme 2：
Specially：The poloxamer and being dissolved in nitro phenyl chloroformate under pyridine room temperature for 1.5 equivalents for taking 1 equivalent carry out instead Should, products therefrom in pyridine is heated to 90 DEG C with appropriate amounts of gelatin polysaccharide by purification and is obtained by the reactionIn the second component it is bright Glue polysaccharide.
Wherein PNC:To nitro phenyl chloroformate；Py：Pyridine
Scheme 2
Description of the drawings
Fig. 1 is that the rapid surgical of the present invention binds the schematic diagram of sealant.
Specific embodiment
As shown in Figure 1, include in rapid surgical provided by the invention bonding sealant 100：It is loaded into the first appearance The first constituent solid powder 11 in device 10, the second component solution 21 being loaded into second container 20 and one are for mixing It closes gel solution precursor and gel is applied directly to the coating stick 30 of surgical site.
Solid powder components in 10 pallet of the first container of closing（First component）11, the solid powder components are Selected from the multi-arm polyethylene glycol with double glutarates-hydroxysuccinimide eater modification（multi-arm PEG-SG）.It is described Multi-arm polyethylene glycol for both arms polyethylene glycol, four arm polyethylene glycol, eight arm polyethylene glycol（2-arm PEG-SG、4-arm PEG-SG、8-arm PEG-SG）, it is preferably four arm polyethylene glycol and eight arm polyethylene glycol.In addition, disguise can be added in end it is suitable The medical dyestuff of FD ＆ C Blue#1 blues of amount facilitates application to increase visuality；
Solution component in 20 syringe of second container or plastics sebific duct of closing（Second component）21, the solution component Solute is selected from modified gelatin polysaccharide.The solvent of solution is the phosphate or borate buffer solution of pH4 to 12.
Before bonding sealant also includes a dauber 30 for dissolving, mixing the first constituent solid and smear gel Solution.
The each component forms the formula of the gel application external member, with the total weight of the formula.The PEG classes The weight percent for closing object is 5% ~ 20%, preferably 7 ~ 15%, and optimal is 9%；The weight percent of the gelatin polysaccharide compound Than being 0.2% ~ 3%, preferably 0.5 ~ 2%, optimal is 1%.It also, can be fast coated on operative site after two component mixes Fast firm sealant hydrogel.
The gel application external member, wherein can also add such as hemostasis class drug, antibiotic medicine, antiviral class drug And the compound medicine being especially composed, with the total weight of above-mentioned formula, the weight percent for adding the drug can be with It is 0.01% ~ 25%.
Tranexamic acid and fibrin ferment can be selected in the addible hemostasis class drug；The addible antibiotics Penicillin, chloramphenicol, tobramycin, gentamicin, amikacin and polymyxins can be selected in drug；Described is addible anti- Virazole, Ganciclovir and acyclovir can be selected in virus type drug.
Specifically used method is as follows：
Dismantle 10 pallet of outer packing and the first container of rapid surgical bonding sealant 100；By second in second container Component solution 21 squeeze/is injected into 10 pallet of the first container；First made with the liquid that is gently mixed in 10 of tail end of coating stick 30 11 solid of component quickly dissolves；With the head end of coating stick 30 suitable mixed solution is dipped from 10 pallet of the first container（Gel Precursor）And gently be coated on action site；Finally, a bit of time is waited for（Between several seconds to tens seconds）Tissue can be formed The hydrogel sealing binder of good adhesion.
Lower specific embodiment is described below so that the present invention is described in more detail：
In following embodiments and comparative example, the properties of rapid surgical bonding sealant measure specific side Method is as follows：
Gelation time test method：Surgical operation bonding sealant external member is opened, is consolidated the first component using the second component solution Body powder fully dissolves and mixed solution is added dropwise in 37 DEG C of bottle, until treating that revolving individual vials liquid does not flow, during record Between be gelation time（Revolving individual vials method）.
Degradation time test method：Surgical operation bonding sealant external member is opened, using the second component solution by first group Solid powder is divided fully to dissolve, hydrogel is placed in simulation physiological environment after gel-forming（That is 37 DEG C of PBS solutions）In, record Degradation time.
Bond strength testing method：Surgical operation bonding sealant external member is opened, using the second component solution by first group Solid powder is divided fully to dissolve and be applied on pigskin substrate, according to YY/T0729.1 tissue adhesives adhesive property test method Part 1：Overlap joint-shear tension carries intensity and is tested.
Cytotoxicity assay：Surgical operation bonding sealant external member is opened, using the second component solution by first group Solid powder is divided fully to dissolve to be placed on cell culture medium, is tested according to GB/T16886.5 prescriptive procedures.
It will more fully illustrate beneficial effects of the present invention by the following examples.
Embodiment 1 is with 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g courages Sterol；Method synthesis of the gelatin that the PEG and 5g molecular weight that 10g molecular weight is 10000 is 5000 through said program one is made 1. rapid surgical binds the gelatin polysaccharide of the modification of the second component of sealant suit, i.e. the cholesterol with PEG chains 1., by 12 phosphate buffer (PBS) of pH value modified gelatin polysaccharide is made into the second component solution.And with single armed molecular weight For（10000）2 arm SG-PEG dry powder be made the first component, wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide： PBS=20：3：79.Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise by sealant suit component Enter in 37 DEG C of bottle, measure its gelation time as 36s；A set of sealant 1. component is taken, using the second component solution by first Constituent solid powder fully dissolves, and hydrogel is placed in simulation physiological environment after gel-forming（That is 37 DEG C of PBS solutions）In, it surveys It is 33 days to obtain its degradation time；Taking a set of sealant, 1. component is fully molten by the first constituent solid powder using the second component solution It solves and is applied on pigskin substrate, measure its adhesion strength as 87N；And its cytotoxicity is had no in cell tests, reach and face The medical requirement of bed.
Embodiment 2
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；1g molecules It measures the method for being the gelatin that 1000 PEG and 1g molecular weight is 1000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（10000）2 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=20：0.2： 79.8.Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise to 37 DEG C by component suit component Bottle in, measure its gelation time as 30s；A set of sealant 1. component is taken, is consolidated the first component using the second component solution Body powder fully dissolves, and hydrogel is placed in simulation physiological environment after gel-forming（That is 37 DEG C of PBS solutions）In, measure its drop It is 37 days to solve the time；Taking a set of sealant, 1. the first constituent solid powder is fully dissolved and applied using the second component solution by component It is 91N to smear on pigskin substrate, measuring its adhesion strength；And its cytotoxicity is had no in cell tests, reach clinical medical It is required that.
Embodiment 3
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；6g molecules It measures the method for being the gelatin that 6000 PEG and 3.5g molecular weight is 3500 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 8 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（8000）2 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：2：83.By This obtains rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by component In, its gelation time is measured as 27s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 39 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 95N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 4
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；3g molecules It measures the method for being the gelatin that 3000 PEG and 2g molecular weight is 2000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 6 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（8000）2 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：0.5： 84.5.Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise to 37 DEG C by component suit component Bottle in, measure its gelation time as 2336s；A set of sealant 1. component is taken, using the second component solution by the first component Solid powder fully dissolves, and hydrogel is placed in simulation physiological environment after gel-forming（That is 37 DEG C of PBS solutions）In, measure it Degradation time is 43 days；Taking a set of sealant, 1. component is fully dissolved the first constituent solid powder simultaneously using the second component solution It is applied on pigskin substrate, measures its adhesion strength as 101N；And its cytotoxicity is had no in cell tests, reach clinical doctor With requiring.
Embodiment 5
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；5g molecules It measures the method for being the gelatin that 5000 PEG and 3g molecular weight is 3000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 7.4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（5000）2 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=9：1：90.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 19s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 47 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 115N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 6
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；6g molecules It measures the method for being the gelatin that 6000 PEG and 3.5g molecular weight is 3500 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 8 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（2000）2 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=7：2：91.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 22s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 44 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 105N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 7
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；3g molecules It measures the method for being the gelatin that 3000 PEG and 2g molecular weight is 2000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 6 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（2000）2 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=7：0.5：92.5. Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant set First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by arrangement In, its gelation time is measured as 25s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 393 days；Taking a set of sealant, 1. the first constituent solid powder is fully dissolved and is applied to using the second component solution by component On pigskin substrate, its adhesion strength is measured as 97N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 8
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；10g molecules It measures the method for being the gelatin that 10000 PEG and 5g molecular weight is 5000 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 12 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（800）2 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=5：3：92.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 28s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 33 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 93N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 9
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；1g molecules It measures the method for being the gelatin that 1000 PEG and 1g molecular weight is 1000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（800）2 arm SG- The first component is made in PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=5：0.2：94.8.By This obtains rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by component In, its gelation time is measured as 33s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 29 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 85N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 10
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；10g molecules It measures the method for being the gelatin that 10000 PEG and 5g molecular weight is 5000 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 12 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（10000）4 The first component is made in arm SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=20：3：79. Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant set First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by arrangement In, its gelation time is measured as 35s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 34 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 96N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 11
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；1g molecules It measures the method for being the gelatin that 1000 PEG and 1g molecular weight is 1000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（10000）4 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=20：0.2： 79.8.Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise to 37 DEG C by component suit component Bottle in, measure its gelation time as 31s；A set of sealant 1. component is taken, is consolidated the first component using the second component solution Body powder fully dissolves, and hydrogel is placed in simulation physiological environment after gel-forming（That is 37 DEG C of PBS solutions）In, measure its drop It is 36 days to solve the time；Taking a set of sealant, 1. the first constituent solid powder is fully dissolved and applied using the second component solution by component It is 102N to smear on pigskin substrate, measuring its adhesion strength；And its cytotoxicity is had no in cell tests, reach clinical medical It is required that.
Embodiment 12
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；6g molecules It measures the method for being the gelatin that 6000 PEG and 3.5g molecular weight is 3500 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 8 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（8000）4 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：2：83.By This obtains rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by component In, its gelation time is measured as 28s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 40 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 107N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 13
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；3g molecules It measures the method for being the gelatin that 3000 PEG and 2g molecular weight is 2000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 6 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（8000）4 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：0.5： 84.5.Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise to 37 DEG C by component suit component Bottle in, measure its gelation time as 22s；A set of sealant 1. component is taken, is consolidated the first component using the second component solution Body powder fully dissolves, and hydrogel is placed in simulation physiological environment after gel-forming（That is 37 DEG C of PBS solutions）In, measure its drop It is 44 days to solve the time；Taking a set of sealant, 1. the first constituent solid powder is fully dissolved and applied using the second component solution by component It is 110N to smear on pigskin substrate, measuring its adhesion strength；And its cytotoxicity is had no in cell tests, reach clinical medical It is required that.
Embodiment 14
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；5g molecules It measures the method for being the gelatin that 5000 PEG and 3g molecular weight is 3000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 7.4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（5000）4 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=9：1：90.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 20s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 49 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 123N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 15
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；6g molecules It measures the method for being the gelatin that 6000 PEG and 3.5g molecular weight is 3500 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 8 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（2000）4 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=7：2：91.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 22s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 47 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 117N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 16
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；3g molecules It measures the method for being the gelatin that 3000 PEG and 2g molecular weight is 2000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 6 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（2000）4 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=7：0.5：92.5. Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant set First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by arrangement In, its gelation time is measured as 27s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 38 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 106N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 17
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；10g molecules It measures the method for being the gelatin that 10000 PEG and 5g molecular weight is 5000 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 12 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（800）4 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=5：3：92.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 29s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 35 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 101N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 18
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；1g molecules It measures the method for being the gelatin that 1000 PEG and 1g molecular weight is 1000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（800）4 arm SG- The first component is made in PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=5：0.2：94.8.By This obtains rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by component In, its gelation time is measured as 31s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 30 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 93N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 19
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；10g molecules It measures the method for being the gelatin that 10000 PEG and 5g molecular weight is 5000 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 12 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（10000）8 The first component is made in arm SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=20：3：79. Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant set First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by arrangement In, its gelation time is measured as 37s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 36 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component On canthus film substrate, its adhesion strength is measured as 105N；And its cytotoxicity is had no in cell tests, reaching clinical medical will It asks.
Embodiment 20
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；1g molecules It measures the method for being the gelatin that 1000 PEG and 1g molecular weight is 1000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（10000）8 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=20：0.2： 79.8.Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise to 37 DEG C by component suit component Bottle in, measure its gelation time as 33s；A set of sealant 1. component is taken, is consolidated the first component using the second component solution Body powder fully dissolves, and hydrogel is placed in simulation physiological environment after gel-forming（That is 37 DEG C of PBS solutions）In, measure its drop It is 39 days to solve the time；Taking a set of sealant, 1. the first constituent solid powder is fully dissolved and applied using the second component solution by component It is 111N to smear on pigskin substrate, measuring its adhesion strength；And its cytotoxicity is had no in cell tests, reach clinical medical It is required that.
Embodiment 21
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；6g molecules It measures the method for being the gelatin that 6000 PEG and 3.5g molecular weight is 3500 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 8 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（8000）8 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：2：83.By This obtains rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by component In, its gelation time is measured as 29s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 41 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 118N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 22
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；3g molecules It measures the method for being the gelatin that 3000 PEG and 2g molecular weight is 2000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 6 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（8000）8 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：0.5： 84.5.Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise to 37 DEG C by component suit component Bottle in, measure its gelation time as 24s；A set of sealant 1. component is taken, is consolidated the first component using the second component solution Body powder fully dissolves, and hydrogel is placed in simulation physiological environment after gel-forming（That is 37 DEG C of PBS solutions）In, measure its drop It is 46 days to solve the time；Taking a set of sealant, 1. the first constituent solid powder is fully dissolved and applied using the second component solution by component It is 123N to smear on pigskin substrate, measuring its adhesion strength；And its cytotoxicity is had no in cell tests, reach clinical medical It is required that.
Embodiment 23
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；5g molecules It measures the method for being the gelatin that 5000 PEG and 3g molecular weight is 3000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 7.4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（5000）8 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=9：1：90.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 20s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 50 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 135N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 24
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；6g molecules It measures the method for being the gelatin that 6000 PEG and 3.5g molecular weight is 3500 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 8 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（2000）8 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=7：2：91.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 22s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 48 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 126N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 25
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；3g molecules It measures the method for being the gelatin that 3000 PEG and 2g molecular weight is 2000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 6 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（2000）8 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=7：0.5：92.5. Thus to obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant set First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by arrangement In, its gelation time is measured as 26s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 39 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 115N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 26
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；10g molecules It measures the method for being the gelatin that 10000 PEG and 5g molecular weight is 5000 through said program one synthesis and rapid surgical is made 1., i.e., the cholesterol modifying gelatin with PEG chains is more for the gelatin polysaccharide of the modification of second component of bonding sealant suit 1. sugar, the second component solution is made by 12 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（800）8 arms The first component is made in SG-PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=5：3：92.Thus Obtain rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit group First constituent solid powder using the second component solution is fully dissolved and mixed solution is added dropwise in 37 DEG C of bottle by part, Its gelation time is measured as 27s；A set of sealant 1. component is taken, it is using the second component solution that the first constituent solid powder is abundant Dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, it is 37 to measure its degradation time My god；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pigskin base by component On piece measures its adhesion strength as 113N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Embodiment 27
With 0.29g p-methyl benzene sulfonic chlorides（TsCl）；0.2g is to nitro phenyl chloroformate（PNC）；0.39g cholesterol；1g molecules It measures the method for being the gelatin that 1000 PEG and 1g molecular weight is 1000 through said program one synthesis rapid surgical is made and stick Close sealant suit the second component modification gelatin polysaccharide 1., i.e., the cholesterol modifying gelatin polysaccharide with PEG chains 1. it is made into the second component solution by 4 phosphate buffer (PBS) of pH value.And using single armed molecular weight as（800）8 arm SG- The first component is made in PEG dry powder, and wherein each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=5：0.2：94.8.By This obtains rapid surgical bonding sealant suit.Take a set of above-mentioned rapid surgical bonding sealant suit First constituent solid powder using the second component solution is fully dissolved and is added dropwise to mixed solution 37 DEG C of bottle by component In, its gelation time is measured as 32s；A set of sealant 1. component is taken, using the second component solution by the first constituent solid powder Fully dissolving, simulation physiological environment is placed in after gel-forming by hydrogel（That is 37 DEG C of PBS solutions）In, measure its degradation time It is 33 days；Taking a set of sealant, 1. the first constituent solid powder using the second component solution is fully dissolved and is applied to pig by component Scytoblastema on piece measures its adhesion strength as 101N；And its cytotoxicity is had no in cell tests, reach clinical medical requirement.
Table one：The embodiment tables of data of sealant 1.
It is real It applies Example Multi-arm PEG arms Number Multi-arm PEG is mono- Arm molecular weight Multi-arm PEG Content（%） Gelatin is more Glycan molecule Amount For modified gelatin PEG molecular weight Gelatin polysaccharide Content（%） It buffers molten Liquid pH value During plastic Between（s） Bonding is strong Degree（N） During decomposition Between（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
Embodiment 28
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 5g molecular weight that 9.8g molecular weight is 9840 are 5000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 12 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（10000）2 arm SG-PEG dry powder the first component, wherein each group sub-prime is made Amount is than being multi-arm PEG：Modified gelatin polysaccharide：PBS=20：3：79.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 28s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 27 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 77N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 29
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 1g molecular weight that 98.8g molecular weight is 8830 are 1000 Method synthesis of the gelatin through said program two the second component of rapid surgical bonding sealant suit be made change Property gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 4 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（10000）2 arm SG-PEG dry powder the first component, wherein each component is made Mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=20：0.2：79.8.Sealant group is binded thus to obtain rapid surgical Part is set with.A set of rapid surgical bonding sealant suit is taken, using the second component solution by the first constituent solid powder It is last fully to dissolve and mixed solution is added dropwise in 37 DEG C of bottle, its gelation time is measured as 23s；Take a set of sealant 1. group Part is fully dissolved the first constituent solid powder using the second component solution, and hydrogel is placed in simulation life after gel-forming Manage environment（That is 37 DEG C of PBS solutions）In, it is 33 days to measure its degradation time；Taking a set of sealant, 1. component is molten using the second component First constituent solid powder is fully dissolved and is applied on pigskin substrate by liquid, measures its adhesion strength as 82N；And it is surveyed in cell Its cytotoxicity is had no in examination, reaches clinical medical requirement.
Embodiment 30
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3.5g molecular weight that 9.68g molecular weight is 9600 be The second component of rapid surgical bonding sealant suit is made in method synthesis of 3500 gelatin through said program two Modification gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., using pH value as 8 phosphate buffer (PBS) it is made into the second component solution.And using single armed molecular weight as（8000）2 arm SG-PEG dry powder the first component is made, wherein Each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：2：83.Sealant is binded thus to obtain rapid surgical Component is set with.A set of rapid surgical bonding sealant suit is taken, using the second component solution by the first constituent solid Powder fully dissolves and mixed solution is added dropwise in 37 DEG C of bottle, measures its gelation time as 20s；Take a set of sealant 1. First constituent solid powder using the second component solution is fully dissolved, hydrogel is placed in simulation after gel-forming by component Physiological environment（That is 37 DEG C of PBS solutions）In, it is 35 days to measure its degradation time；Taking a set of sealant, 1. component uses the second component First constituent solid powder is fully dissolved and is applied on pigskin substrate by solution, measures its adhesion strength as 84N；And in cell Its cytotoxicity is had no in test, reaches clinical medical requirement.
Embodiment 31
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 2g molecular weight that 9g molecular weight is 9000 be 2000 it is bright The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the glue through said program two 2. 2., i.e., gelatin polysaccharide that gelatin polysaccharide is modified by poloxamer, the is made by 6 phosphate buffer (PBS) of pH value Two component solutions.And using single armed molecular weight as（8000）2 arm SG-PEG dry powder the first component, wherein each component mass ratio is made For multi-arm PEG：Modified gelatin polysaccharide：PBS=15：0.5：84.5.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 14s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 39 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 91N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 32
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3g molecular weight that 9.3g molecular weight is 9300 are 3000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 7.4 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（10000）2 arm SG-PEG dry powder the first component, wherein each component is made Mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=9：1：90.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 12s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 43 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 103N；And in cell tests In have no its cytotoxicity, reach clinical medical requirement.
Embodiment 33
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3.5g molecular weight that 9.6g molecular weight is 9600 are 3500 Method synthesis of the gelatin through said program two the second component of rapid surgical bonding sealant suit be made change Property gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 8 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（2000）2 arm SG-PEG dry powder the first component, wherein each group sub-prime is made Amount is than being multi-arm PEG：Modified gelatin polysaccharide：PBS=7：2：91.Thus to obtain rapid surgical bonding sealant suit. A set of rapid surgical bonding sealant suit is taken, it is using the second component solution that the first constituent solid powder is fully molten It solves and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 15s；A set of sealant 1. component is taken, is used Second component solution fully dissolves the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming （That is 37 DEG C of PBS solutions）In, it is 38 days to measure its degradation time；Take a set of sealant 1. component using the second component solution by the One constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 97N；And in cell tests not See its cytotoxicity, reach clinical medical requirement.
Embodiment 34
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 2g molecular weight that 9g molecular weight is 9000 be 2000 it is bright The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the glue through said program two 2. 2., i.e., gelatin polysaccharide that gelatin polysaccharide is modified by poloxamer, the is made by 6 phosphate buffer (PBS) of pH value Two component solutions.And using single armed molecular weight as（2000）2 arm SG-PEG dry powder the first component, wherein each component mass ratio is made For multi-arm PEG：Modified gelatin polysaccharide：PBS=7：0.5：92.5.Thus to obtain rapid surgical bonding sealant suit. A set of rapid surgical bonding sealant suit is taken, it is using the second component solution that the first constituent solid powder is fully molten It solves and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 18s；A set of sealant 1. component is taken, is used Second component solution fully dissolves the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming （That is 37 DEG C of PBS solutions）In, it is 34 days to measure its degradation time；Take a set of sealant 1. component using the second component solution by the One constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 86N；And in cell tests not See its cytotoxicity, reach clinical medical requirement.
Embodiment 35
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 5g molecular weight that 9.8g molecular weight is 9840 are 5000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 12 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（800）2 arm SG-PEG dry powder the first component, wherein each component quality is made Than for multi-arm PEG：Modified gelatin polysaccharide：PBS=5：3：92.Thus to obtain rapid surgical bonding sealant suit.It takes A set of rapid surgical bonding sealant suit, is fully dissolved the first constituent solid powder using the second component solution And be added dropwise to mixed solution in 37 DEG C of bottle, its gelation time is measured as 21s；A set of sealant 1. component is taken, uses Two component solutions fully dissolve the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming（I.e. 37 DEG C of PBS solutions）In, it is 27 days to measure its degradation time；Taking a set of sealant, 1. component uses the second component solution by first Constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 82N；And it is had no in cell tests Its cytotoxicity reaches clinical medical requirement.
Embodiment 36
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 1g molecular weight that 8.8g molecular weight is 8830 are 1000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 4 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（800）2 arm SG-PEG dry powder the first component, wherein each component quality is made Than for multi-arm PEG：Modified gelatin polysaccharide：PBS=5：0.2：94.8.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 26s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 25 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 73N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 37
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 5g molecular weight that 9.8g molecular weight is 9840 are 5000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 12 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（10000）4 arm SG-PEG dry powder the first component, wherein each group sub-prime is made Amount is than being multi-arm PEG：Modified gelatin polysaccharide：PBS=20：3：79.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 29s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 30 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 84N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 38
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 1g molecular weight that 98.8g molecular weight is 8830 are 1000 Method synthesis of the gelatin through said program two the second component of rapid surgical bonding sealant suit be made change Property gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 4 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（10000）4 arm SG-PEG dry powder the first component, wherein each component is made Mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=20：0.2：79.8.Sealant group is binded thus to obtain rapid surgical Part is set with.A set of rapid surgical bonding sealant suit is taken, using the second component solution by the first constituent solid powder It is last fully to dissolve and mixed solution is added dropwise in 37 DEG C of bottle, its gelation time is measured as 24s；Take a set of sealant 1. group Part is fully dissolved the first constituent solid powder using the second component solution, and hydrogel is placed in simulation life after gel-forming Manage environment（That is 37 DEG C of PBS solutions）In, it is 32 days to measure its degradation time；Taking a set of sealant, 1. component is molten using the second component First constituent solid powder is fully dissolved and is applied on pigskin substrate by liquid, measures its adhesion strength as 94N；And it is surveyed in cell Its cytotoxicity is had no in examination, reaches clinical medical requirement.
Embodiment 39
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3.5g molecular weight that 9.68g molecular weight is 9600 be The second component of rapid surgical bonding sealant suit is made in method synthesis of 3500 gelatin through said program two Modification gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., using pH value as 8 phosphate buffer (PBS) it is made into the second component solution.And using single armed molecular weight as（8000）4 arm SG-PEG dry powder the first component is made, wherein Each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：2：83.Sealant is binded thus to obtain rapid surgical Component is set with.A set of rapid surgical bonding sealant suit is taken, using the second component solution by the first constituent solid Powder fully dissolves and mixed solution is added dropwise in 37 DEG C of bottle, measures its gelation time as 20s；Take a set of sealant 1. First constituent solid powder using the second component solution is fully dissolved, hydrogel is placed in simulation after gel-forming by component Physiological environment（That is 37 DEG C of PBS solutions）In, it is 36 days to measure its degradation time；Taking a set of sealant, 1. component uses the second component First constituent solid powder is fully dissolved and is applied on pigskin substrate by solution, measures its adhesion strength as 98N；And in cell Its cytotoxicity is had no in test, reaches clinical medical requirement.
Embodiment 40
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 2g molecular weight that 9g molecular weight is 9000 be 2000 it is bright The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the glue through said program two 2. 2., i.e., gelatin polysaccharide that gelatin polysaccharide is modified by poloxamer, the is made by 6 phosphate buffer (PBS) of pH value Two component solutions.And using single armed molecular weight as（8000）4 arm SG-PEG dry powder the first component, wherein each component mass ratio is made For multi-arm PEG：Modified gelatin polysaccharide：PBS=15：0.5：84.5.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 15s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 40 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 102N；And in cell tests In have no its cytotoxicity, reach clinical medical requirement.
Embodiment 41
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3g molecular weight that 9.3g molecular weight is 9300 are 3000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 7.4 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（10000）4 arm SG-PEG dry powder the first component, wherein each component is made Mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=9：1：90.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 11s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 45 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 113N；And in cell tests In have no its cytotoxicity, reach clinical medical requirement.
Embodiment 42
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3.5g molecular weight that 9.6g molecular weight is 9600 are 3500 Method synthesis of the gelatin through said program two the second component of rapid surgical bonding sealant suit be made change Property gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 8 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（2000）4 arm SG-PEG dry powder the first component, wherein each group sub-prime is made Amount is than being multi-arm PEG：Modified gelatin polysaccharide：PBS=7：2：91.Thus to obtain rapid surgical bonding sealant suit. A set of rapid surgical bonding sealant suit is taken, it is using the second component solution that the first constituent solid powder is fully molten It solves and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 16s；A set of sealant 1. component is taken, is used Second component solution fully dissolves the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming （That is 37 DEG C of PBS solutions）In, it is 42 days to measure its degradation time；Take a set of sealant 1. component using the second component solution by the One constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 106N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 43
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 2g molecular weight that 9g molecular weight is 9000 be 2000 it is bright The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the glue through said program two 2. 2., i.e., gelatin polysaccharide that gelatin polysaccharide is modified by poloxamer, the is made by 6 phosphate buffer (PBS) of pH value Two component solutions.And using single armed molecular weight as（2000）4 arm SG-PEG dry powder the first component, wherein each component mass ratio is made For multi-arm PEG：Modified gelatin polysaccharide：PBS=7：0.5：92.5.Thus to obtain rapid surgical bonding sealant suit. A set of rapid surgical bonding sealant suit is taken, it is using the second component solution that the first constituent solid powder is fully molten It solves and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 19s；A set of sealant 1. component is taken, is used Second component solution fully dissolves the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming （That is 37 DEG C of PBS solutions）In, it is 34 days to measure its degradation time；Take a set of sealant 1. component using the second component solution by the One constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 94N；And in cell tests not See its cytotoxicity, reach clinical medical requirement.
Embodiment 44
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 5g molecular weight that 9.8g molecular weight is 9840 are 5000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 12 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（800）4 arm SG-PEG dry powder the first component, wherein each component quality is made Than for multi-arm PEG：Modified gelatin polysaccharide：PBS=5：3：92.Thus to obtain rapid surgical bonding sealant suit.It takes A set of rapid surgical bonding sealant suit, is fully dissolved the first constituent solid powder using the second component solution And be added dropwise to mixed solution in 37 DEG C of bottle, its gelation time is measured as 23s；A set of sealant 1. component is taken, uses Two component solutions fully dissolve the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming（I.e. 37 DEG C of PBS solutions）In, it is 30 days to measure its degradation time；Taking a set of sealant, 1. component uses the second component solution by first Constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 90N；And it is had no in cell tests Its cytotoxicity reaches clinical medical requirement.
Embodiment 45
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 1g molecular weight that 8.8g molecular weight is 8830 are 1000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 4 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（800）4 arm SG-PEG dry powder the first component, wherein each component quality is made Than for multi-arm PEG：Modified gelatin polysaccharide：PBS=5：0.2：94.8.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 24s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 26 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 84N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 46
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 5g molecular weight that 9.8g molecular weight is 9840 are 5000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 12 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（10000）8 arm SG-PEG dry powder the first component, wherein each group sub-prime is made Amount is than being multi-arm PEG：Modified gelatin polysaccharide：PBS=20：3：79.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 30s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 32 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 93N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 47
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 1g molecular weight that 98.8g molecular weight is 8830 are 1000 Method synthesis of the gelatin through said program two the second component of rapid surgical bonding sealant suit be made change Property gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 4 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（10000）8 arm SG-PEG dry powder the first component, wherein each component is made Mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=20：0.2：79.8.Sealant group is binded thus to obtain rapid surgical Part is set with.A set of rapid surgical bonding sealant suit is taken, using the second component solution by the first constituent solid powder It is last fully to dissolve and mixed solution is added dropwise in 37 DEG C of bottle, its gelation time is measured as 25s；Take a set of sealant 1. group Part is fully dissolved the first constituent solid powder using the second component solution, and hydrogel is placed in simulation life after gel-forming Manage environment（That is 37 DEG C of PBS solutions）In, it is 33 days to measure its degradation time；Taking a set of sealant, 1. component is molten using the second component First constituent solid powder is fully dissolved and is applied on pigskin substrate by liquid, measures its adhesion strength as 99N；And it is surveyed in cell Its cytotoxicity is had no in examination, reaches clinical medical requirement.
Embodiment 48
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3.5g molecular weight that 9.68g molecular weight is 9600 be The second component of rapid surgical bonding sealant suit is made in method synthesis of 3500 gelatin through said program two Modification gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., using pH value as 8 phosphate buffer (PBS) it is made into the second component solution.And using single armed molecular weight as（8000）8 arm SG-PEG dry powder the first component is made, wherein Each component mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=15：2：83.Sealant is binded thus to obtain rapid surgical Component is set with.A set of rapid surgical bonding sealant suit is taken, using the second component solution by the first constituent solid Powder fully dissolves and mixed solution is added dropwise in 37 DEG C of bottle, measures its gelation time as 20s；Take a set of sealant 1. First constituent solid powder using the second component solution is fully dissolved, hydrogel is placed in simulation after gel-forming by component Physiological environment（That is 37 DEG C of PBS solutions）In, it is 36 days to measure its degradation time；Taking a set of sealant, 1. component uses the second component First constituent solid powder is fully dissolved and is applied on pigskin substrate by solution, measures its adhesion strength as 110N；And thin Its cytotoxicity is had no in born of the same parents' test, reaches clinical medical requirement.
Embodiment 49
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 2g molecular weight that 9g molecular weight is 9000 be 2000 it is bright The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the glue through said program two 2. 2., i.e., gelatin polysaccharide that gelatin polysaccharide is modified by poloxamer, the is made by 6 phosphate buffer (PBS) of pH value Two component solutions.And using single armed molecular weight as（8000）8 arm SG-PEG dry powder the first component, wherein each component mass ratio is made For multi-arm PEG：Modified gelatin polysaccharide：PBS=15：0.5：84.5.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 15s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 42 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 115N；And in cell tests In have no its cytotoxicity, reach clinical medical requirement.
Embodiment 50
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3g molecular weight that 9.3g molecular weight is 9300 are 3000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 7.4 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（10000）8 arm SG-PEG dry powder the first component, wherein each component is made Mass ratio is multi-arm PEG：Modified gelatin polysaccharide：PBS=9：1：90.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 13s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 45 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 128N；And in cell tests In have no its cytotoxicity, reach clinical medical requirement.
Embodiment 51
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 3.5g molecular weight that 9.6g molecular weight is 9600 are 3500 Method synthesis of the gelatin through said program two the second component of rapid surgical bonding sealant suit be made change Property gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., match by 8 phosphate buffer (PBS) of pH value Into the second component solution.And using single armed molecular weight as（2000）8 arm SG-PEG dry powder the first component, wherein each group sub-prime is made Amount is than being multi-arm PEG：Modified gelatin polysaccharide：PBS=7：2：91.Thus to obtain rapid surgical bonding sealant suit. A set of rapid surgical bonding sealant suit is taken, it is using the second component solution that the first constituent solid powder is fully molten It solves and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 14s；A set of sealant 1. component is taken, is used Second component solution fully dissolves the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming （That is 37 DEG C of PBS solutions）In, it is 42 days to measure its degradation time；Take a set of sealant 1. component using the second component solution by the One constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 116N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 52
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 2g molecular weight that 9g molecular weight is 9000 be 2000 it is bright The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the glue through said program two 2. 2., i.e., gelatin polysaccharide that gelatin polysaccharide is modified by poloxamer, the is made by 6 phosphate buffer (PBS) of pH value Two component solutions.And using single armed molecular weight as（2000）8 arm SG-PEG dry powder the first component, wherein each component mass ratio is made For multi-arm PEG：Modified gelatin polysaccharide：PBS=7：0.5：92.5.Thus to obtain rapid surgical bonding sealant suit. A set of rapid surgical bonding sealant suit is taken, it is using the second component solution that the first constituent solid powder is fully molten It solves and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 19s；A set of sealant 1. component is taken, is used Second component solution fully dissolves the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming （That is 37 DEG C of PBS solutions）In, it is 35 days to measure its degradation time；Take a set of sealant 1. component using the second component solution by the One constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 106N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Embodiment 53
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 5g molecular weight that 9.8g molecular weight is 9840 are 5000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 12 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（800）8 arm SG-PEG dry powder the first component, wherein each component quality is made Than for multi-arm PEG：Modified gelatin polysaccharide：PBS=5：3：92.Thus to obtain rapid surgical bonding sealant suit.It takes A set of rapid surgical bonding sealant suit, is fully dissolved the first constituent solid powder using the second component solution And be added dropwise to mixed solution in 37 DEG C of bottle, its gelation time is measured as 22s；A set of sealant 1. component is taken, uses Two component solutions fully dissolve the first constituent solid powder, and hydrogel is placed in simulation physiological environment after gel-forming（I.e. 37 DEG C of PBS solutions）In, it is 33 days to measure its degradation time；Taking a set of sealant, 1. component uses the second component solution by first Constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 101N；And in cell tests not See its cytotoxicity, reach clinical medical requirement.
Embodiment 54
0.2g is to nitro phenyl chloroformate（PNC）；The poloxamer and 1g molecular weight that 8.8g molecular weight is 8830 are 1000 The modification of the second component of rapid surgical bonding sealant suit is made in method synthesis of the gelatin through said program two Gelatin polysaccharide 2., i.e., by poloxamer be modified gelatin polysaccharide 2., be made by 4 phosphate buffer (PBS) of pH value Second component solution.And using single armed molecular weight as（800）8 arm SG-PEG dry powder the first component, wherein each component quality is made Than for multi-arm PEG：Modified gelatin polysaccharide：PBS=5：0.2：94.8.Sealant set is binded thus to obtain rapid surgical Dress.A set of rapid surgical bonding sealant suit is taken, is filled the first constituent solid powder using the second component solution Divide and dissolve and mixed solution is added dropwise in 37 DEG C of bottle, measure its gelation time as 26s；A set of sealant 1. component is taken, The first constituent solid powder is fully dissolved using the second component solution, hydrogel is placed in simulation physiologic ring after gel-forming Border（That is 37 DEG C of PBS solutions）In, it is 28 days to measure its degradation time；Taking a set of sealant, 1. component will using the second component solution First constituent solid powder is fully dissolved and is applied on pigskin substrate, measures its adhesion strength as 93N；And in cell tests It has no its cytotoxicity, reaches clinical medical requirement.
Table two：The embodiment tables of data of sealant 2.
It is real It applies Example Multi-arm PEG arms Number Multi-arm PEG is mono- Arm molecular weight Multi-arm PEG Content（%） Gelatin is more Glycan molecule Amount For modified gelatin Poloxamer molecular weight Gelatin polysaccharide Content（%） It buffers molten Liquid pH value Plastic Time （s） Bonding Intensity （N） Resolving time （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
The 8 arm PEG dry powder that the single armed molecular weight for selecting 0.9g is 800 are as the first component；Using tri- lysines of 0.02g and pH as The second component solution that 7.4 phosphate buffer solution is made into.Its mass ratio is PEG：Three lysines：Phosphate buffer=9： 0.2：90.8.Sealing binder performance and clinical research show：Binder gelation time is sealed as 14s, adhesive strength 63N, Flexility reaches requirement, does not find cytotoxicity, and can thoroughly decompose after 2 days, reaches clinical medical requirement.
Comparative example 2
The 8 arm PEG dry powder that the single armed molecular weight for selecting 0.9g is 5000 are as the first component；Using tri- lysines of 0.1g and pH as The second component solution that 7.4 phosphate buffer solution is made into.Its mass ratio is PEG：Three lysines：Phosphate buffer=9： 1：90.Sealing binder performance and clinical research show：Binder gelation time is sealed as 8s, adhesive strength 77N, flexibility Requirement can be reached, cytotoxicity is not found, and can thoroughly decompose after 4 days, reach clinical medical requirement.
Comparative example 3
The 8 arm PEG dry powder that the single armed molecular weight for selecting 2g is 10000 are as the first component；Using tri- lysines of 0.3g and pH as 12 The second component solution for being made into of phosphate buffer solution.Its mass ratio is PEG：Three lysines：Phosphate buffer=20：3： 77.Sealing binder performance and clinical research show：Binder gelation time is sealed as 15s, adhesive strength 65N, flexibility Requirement can be reached, cytotoxicity is not found, and can thoroughly decompose after 3 days, reach clinical medical requirement.
Find that each embodiment effect is better than comparative example effect after tested, wherein comparative example gelation time is too short, is unfavorable for Sealant is mixed and is used；And if overlong time, using effect can be influenced, increases difficulty for operation.Through verifying into repeatedly The glue time should be controlled within 5 ~ 50s, wherein it is preferred that 10 ~ 30s, and optimal time is 13s, can not only make sealing in this time Agent first part and second part are sufficiently mixed, and can be implemented on operative site at once；In addition, the bonding of each embodiment is strong Degree is above comparative example, and more conducively postoperative sealing uses；Finally, the resolving time of embodiment supports postoperative wound to be cured enough It closes, according to the postoperative universal law of patient, general postoperative wound healing needs 25 days or so, but because of individual difference, part sufferer wound Mouth healing time is longer, and for such case, then the resolving time, the longer the better, to be enough buttressing operation wound healing, and it is right Ratio effect is very different.
The above, only part specific embodiment of the invention, but protection scope of the present invention is not limited thereto, Any change or replacement expected without creative work, should be covered by the protection scope of the present invention.Therefore, it is of the invention Protection domain should be subject to the protection domain that is limited of claims.

Claims (11)

1. a kind of rapid surgical bonding sealant suit, including：
a）The first component in the first container of closing, first component be solid powder components, the solid powder group The multi-arm polyethylene glycol with double glutarates-hydroxysuccinimide eater modification is selected from, the multi-arm polyethylene glycol is selected from Both arms polyethylene glycol, four arm polyethylene glycol or eight arm polyethylene glycol are preferably selected from four arm polyethylene glycol or eight arm polyethylene glycol,
b）The second component in the second container of closing, second component be solution component, the solute of the solution component Solvent selected from modified gelatin polysaccharide and the solution component is biological buffer solutions；
c）The component suit is also comprising dauber, before the first component of mixing and the second component and smearing gel Solution；
Wherein,
First and second component collectively forms the formula of the rapid surgical bonding sealant suit, is matched with described The total weight of side, the weight percent of multi-arm polyethylene glycol that there are double glutarates-hydroxyl amber glass imide esters to modify Than being 5% ~ 20%, preferably 7 ~ 15%, optimal is 9%；The weight percent of the gelatin polysaccharide of the modification is 0.2% ~ 3%, preferably It is 0.5 ~ 2%, optimal is 1%；The weight percent of the biological buffer solutions is 77% ~ 94.8%, preferably 83% ~ 92.5%, optimal It is 90%.
2. rapid surgical bonding sealant suit as described in claim 1, wherein the first container is support Disk and/or the second container are sebific duct or syringe.
3. rapid surgical bonding sealant suit as described in claim 1, wherein, the biological buffer solutions Selected from phosphate or borate buffer solution.
4. rapid surgical bonding sealant suit as described in claim 3, wherein, the buffer solution PH value is 4 to 12, preferably 6 ~ 8, and optimal is 7.4.
5. rapid surgical bonding sealant suit as described in claim 1, wherein, in the solution component The modification gelatin polysaccharide be selected from following 2 kinds modified gelatin polysaccharide：Cholesterol modifying gelatin with PEG chains is more Sugar orThe gelatin polysaccharide being modified by poloxamer.
6. rapid surgical bonding sealant suit as described in claim 5, wherein the gelatin of the modification is more Sugar weight average molecular weight before modified is 1000 to 5000 dalton, preferably 2000 ~ 3500, optimal is 3000；Modified gelatin is more SugarIn for modified gelatin polysaccharide PEG molecular weight for 1000 ~ 10000, wherein it is preferred that 3000 ~ 6000, optimal is 5000, is changed The gelatin polysaccharide of propertyIn for modified gelatin polysaccharide poloxamer molecular weight for 8840 ~ 9840, preferably 9000 ~ 9600, most Excellent is 9300.
7. rapid surgical as described in claim 1 bonding sealant suit, wherein, first component it is more The single armed weight average molecular weight of arm PEG be 800 to 10000 dalton, preferably 2000 ~ 8000, wherein optimal is 5000.
8. rapid surgical bonding sealant suit as described in claim 1, wherein rapid surgical bind Hemostasis class drug, antibiotic medicine, antiviral class drug are further included in the first component or the second component of sealant suit Or their combination.
9. rapid surgical bonding sealant suit as described in claim 1, wherein, first constituent solid Medical dyestuff is further included in powder to increase the operability that sealant uses.
10. rapid surgical bonding sealant suit as described in claim 1, wherein, first component is consolidated The medical dyestuff that body powder includes is selected from FD ＆ C Blue#1 blue dyes.
11. rapid surgical bonding sealant suit as described in claim 1, wherein, the dauber is Medical cotton stick or polyethylene foamed, wherein dauber one end are for two kinds of precursor solutions of mixing；The other end is responsible for will be mixed It closes uniform solution and is applied to operative site, to form gel in surgical site, play sealing effect.
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