CN114533944A - Elastomer tissue sealant based on natural compound and preparation method thereof - Google Patents
Elastomer tissue sealant based on natural compound and preparation method thereof Download PDFInfo
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
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Abstract
The invention discloses an elastomer tissue sealant based on natural compounds, which consists of A, B components, wherein the A component consists of a polymer component consisting of methacryloylated protein and methacryloylated polysaccharide and a photoinitiator, and the B component consists of trivalent chromium salt and amino acid. The invention also discloses a preparation method of the tissue sealant. The elastomer tissue sealant disclosed by the invention not only has all components of natural compounds, has controllable biodegradability, good biocompatibility and low cytotoxicity and is safe to use, but also can form a more stable multi-element and multi-network polymer through a complex crosslinking reaction between trivalent chromium ions and amino acids, proteins and polysaccharide macromolecules under the initiation of a photoinitiator so as to endow the sealant with higher adhesive strength and tensile strength, so that the sealant can be widely used for anastomosis of surgical wound surfaces, connection of tissues such as blood vessels, nerves and the like, and can replace thread suturing in surgeries so as to be suitable for sealing of tissues such as wounds and the like.
Description
Technical Field
The invention belongs to the technical field of tissue sealant and preparation thereof, and particularly relates to an elastomer tissue sealant based on a natural compound and a preparation method thereof. The elastic body comprises components such as protein, polysaccharide, amino acid and the like, is formed by covalent crosslinking and coordination crosslinking of trivalent chromium, has good elasticity, high adhesive force and effective adhesiveness to a wet tissue, can replace a surgical suture or an anastomat, is used for wound surface sealing, anastomosis of tissues such as blood vessels and nerves and adhesion between an implant and the tissue in the surgical process, and is particularly suitable for minimally invasive surgery and surgical robot minimally invasive surgery.
Background
Current techniques for reattaching and sealing tissue after surgery, such as suturing, fulguration, and stapling, suffer from a number of drawbacks. Among these, the use of sutures to close wounds is not only time consuming, but can also result in leakage of body fluids and air, causing secondary tissue damage or infection. In minimally invasive surgery and robotic surgery, surgical suturing is the most important factor affecting the quality and efficiency of the surgery.
The tissue sealant is a modern surgical biomaterial which is rapidly developed in the last decade, is a novel functional material for replacing the traditional surgical suture, also brings an ideal replacement method for the closure of surgical wounds, and is popular because the implementation procedure is simple, the time is short, the pain to patients is little, and the removal is not needed.
Tissue sealants currently being researched and produced are made primarily from synthetic polymers and natural polymers, which mainly include proteins and natural polysaccharides and their complexes, such as:
(I) synthetic polymer sealants
Synthetic polymeric sealants have easily improved, generally higher mechanical strength and tissue bonding characteristics than naturally derived sealants. However, the potential cytotoxicity of the medicine is easy to generate the defects of sensitivity to wet tissues, chronic inflammation and the like, so that the medicine has safety in long-term use. Representative synthetic polymer sealants are Polyurethane (PU), polyethylene glycol (PEG), and polyvinyl alcohol and derivatives thereof.
(II) Natural protein-based sealants
Sealants based on natural proteins and derivatives thereof have been reported in a number of studies (Jackson MR. the American Journal of surgery.2001; 182: S1-S7; Duarte AP, Coelho JF, Bordado JC, Cidade MT, Gil MH. prog. Polymer. Sci.2012; 37: 1031. minus 1050; Chao H-H, Torchiana DF. Journal of Cardiac surgery.2003; 18: 500. minus 503; Ishia M, Nakanishi K, Ono K, Sato M, Kikuchi M, Saito Y, Yura H, Matsui T, Hattori H, Uenoyama M, Kurita A. biomaterials.2002; 23: 833-. Although natural proteins have the advantages of good biocompatibility, no cytotoxicity basically, and being degradable in vivo, natural protein sealants have the risks of insufficient adhesion performance, low adhesion strength, slow reaction rate, easy propagation of biological diseases, and the like, and are expensive. Representative natural protein sealants include fibrin (fibrin), Collagen or gelatin (Collagen or gelatin), serum albumin (albumin) and derivatives thereof.
(III) Natural polysaccharide-based sealants
Natural glycans are a large series of biopolymers, which consist of the polymerization of monosaccharides (sugars) in different combinations. Polysaccharides, a natural polymer, have been widely used in a variety of medical, pharmaceutical and food applications. The main components include chitosan (chitosan), dextran (dextran), Chondroitin sulfate (Chondroitin sulfate), etc. However, glycans alone do not fulfill the primary function of the sealant, and their primary use is as an adjunct ingredient to protein sealants.
To date, no product has been officially used to replace clinical sutures, mainly because various sealants can not fully meet the comprehensive and extremely strict performance requirements of clinical application on the sealant. These requirements mainly include: adhesive strength, adhesive reaction speed, adhesive surface elasticity, functional reliability, biocompatibility, biosafety, biodegradability, use convenience, traceability of raw materials and the like.
Disclosure of Invention
The invention aims to provide a novel elastomer tissue sealant based on natural compounds, aiming at the current situation that the prior art does not completely meet the clinical suture sealant.
It is another object of the present invention to provide a process for the preparation of the above novel natural compound based elastomeric tissue sealants.
The invention provides an elastomer tissue sealant based on natural compounds, which is characterized in that the elastomer tissue sealant is composed of A, B components, wherein the A component consists of a polymer component composed of methacrylic acylated protein and methacrylic acylated polysaccharide and a photoinitiator, the B component consists of trivalent chromium salt and amino acid, the mass volume ratio content of the methacrylic acylated protein in the A component is 10-30%, the mass content of the methacrylic acylated polysaccharide is 1-10% of the mass ratio content of the methacrylic acylated protein, the mass content of the photoinitiator is 0.1-0.5% of the mass ratio of the methacrylic acylated protein, the mass volume ratio of the trivalent chromium salt in the B component calculated by chromium ions is 0.1-0.5%, and the mass of the amino acid is 0.5-1 time of the mass of the chromium ions, when in use, the mixing ratio of the A, B component is that the mass of the chromium ions in the B component is 0.01-0.05% of the mass of the methacrylic acylated protein in the A component.
The methacrylated protein in the elastomer tissue sealant is at least one of methacrylated collagen, methacrylated gelatin and methacrylated casein.
The methacrylated polysaccharide in the elastomer tissue sealant is at least one of methacrylated chondroitin sulfate, methacrylated hyaluronic acid and methacrylated chitosan.
The amino acid in the elastomer tissue sealant is at least one of tyrosine, hydroxyproline and hydroxylysine. Tyrosine and hydroxyproline are preferred.
The trivalent chromium salt in the elastomer tissue sealant is at least one of chromium sulfate and chromium chloride. Chromium sulfate is preferred.
The photoinitiator described in the above elastomer tissue sealant is photoinitiator 819 [ phenylbis (2,4, 6-trimethylbenzoyl) phosphine oxide ] or photoinitiator LAP [ phenyl-2, 4, 6-trimethylbenzoyl lithium phosphite ], preferably photoinitiator LAP.
The invention provides a preparation method of the novel elastomer tissue sealant based on the natural compound, which comprises the following process steps and conditions:
(1) firstly, carrying out methacrylation reaction on protein and polysaccharide respectively according to the prior method to prepare and purify methacrylated protein and methacrylated polysaccharide, then mixing the methacrylated polysaccharide with the mass being 1-10% of the mass of the obtained methacrylated protein, adding 0.01M phosphate buffer solution with the mass volume concentration of 0.1-0.5% of photoinitiator for dissolution, uniformly mixing the dissolved methacrylated protein with the mass volume concentration being 10-30% (w/v) to serve as a component A, and refrigerating the component A in a dark place for later use;
(2) firstly, the trivalent chromium salt and the amino acid are mixed according to the following chromium ion: mass of amino acid 1: (0.5-1), dissolving in 0.01M phosphate buffer solution, and preparing into component B solution with trivalent chromium ion mass volume ratio concentration of 0.1-0.5% for later use;
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in 100 parts by volume: 1-3, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of a tissue to be bonded;
(4) the adhesive side coated with the AB mixture was closed and irradiated with light of 400-410nm wavelength for 10-30 seconds.
10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in 100 parts by volume: 1-3, then uniformly coating the mixture on the surface of the tissue to be bonded, and then irradiating the surface of the tissue to be bonded for 10-30 seconds by using a light source with the wavelength of 400-410nm, preferably 405nm, thus completing the crosslinking reaction.
The methacrylated protein used in the above method is at least one of methacrylated gelatin and methacrylated casein.
The methacryloylated polysaccharide used in the above method is at least one of methacryloylated chondroitin sulfate, methacryloylated hyaluronic acid, and methacryloylated chitosan.
The amino acid used in the above method is at least one of tyrosine, hydroxyproline and hydroxylysine. Tyrosine and hydroxyproline are preferred.
The trivalent chromium salt used in the above method is at least one of chromium sulfate and chromium chloride. Chromium sulfate is preferred.
The initiator used in the above process is a photoinitiator 819 [ phenylbis (2,4, 6-trimethylbenzoyl) phosphine oxide ] or a photoinitiator LAP [ phenyl-2, 4, 6-trimethylbenzoyl lithium phosphite ], preferably a photoinitiator LAP.
The existing methods for separately performing the methacrylation reaction on the protein and the polysaccharide in the above methods are A high additive and natural derived chemicals, Alexander Assmann et al biomaterials140,2017, p 115-127.
The invention has the following positive effects:
1. the elastomer tissue sealant provided by the invention not only contains all natural compounds, but also introduces trivalent chromium ions (Cr) on the basis of containing methacryloylated protein, methacryloylated polysaccharide and amino acid+3) And the crosslinking between the polymers can be realized by the initiation of the photoinitiator, so that the tensile strength of the sealant can be improved, and the sealant is suitable for sealing tissues such as wounds and the like.
2. The elastomer tissue sealant provided by the invention is endowed with higher adhesive strength by introducing tyrosine and other hydroxy amino acids and by the complexation crosslinking reaction between trivalent chromium ions and amino acids, proteins and polysaccharide macromolecules, so that the elastomer tissue sealant can be widely used for anastomosis of surgical wound surfaces, connection of tissues such as blood vessels, nerves and the like, and can replace suture in surgeries.
3. Because the effectiveness and stability of the complexation reaction of the chromium ions, the amino acids and the proteins are superior to those of other known metal ions, the amino acids can be firmly combined with the proteins and the polysaccharides to form a more stable multi-element and multi-network polymer, and the adhesive strength and the stability of the tissue sealant are improved.
4. All the components used in the invention are natural compounds, and the chromium ions have biological safety, so the elastomer tissue sealant not only has controllable biodegradability and good biocompatibility, but also has low cytotoxicity and safe use.
Detailed Description
The following examples are given to further illustrate the invention. It should be noted that the following examples are not to be construed as limiting the scope of the present invention, and that the skilled person in this field could make modifications and variations of the present invention without departing from the spirit or scope of the present invention.
Example 1
(1) Firstly, performing methacrylation reaction and purification on gelatin and chitosan respectively according to a method disclosed by the prior document (A high adhesive and natural adhesive mineral, Alexander Assmann et al biomaterials140,2017, p115-127), then mixing 1 part by mass of methacrylated chitosan and 100 parts by mass of methacrylated gelatin, adding the mixture into 1000ml of 0.01M phosphate buffer solution containing 1 part by mass of photoinitiator LAP, stirring and dissolving at 40 ℃ to obtain a component A solution with the mass volume concentration ratio of the dissolved methacrylated gelatin of 10%, and refrigerating the solution in the dark for later use;
(2) firstly, chromium sulfate [ Cr ]2(SO4)3 12H2O)]And tyrosine according to chromium ion: tyrosine mass 2: 1 proportion, and then dissolving in 2000ml of 0.01M phosphate buffer solution to obtain a B component solution with the trivalent chromium ion content of 0.1% (w/v) for later use.
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in 100 parts by volume: 1, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of a tissue to be bonded;
(4) closing the adhesive surface coated with the AB mixed component, and irradiating for 10 seconds by using a light source with the wavelength of 400 nm.
Example 2
(1) Firstly, performing methacrylation reaction and purification on casein and chitosan respectively according to a method disclosed by the existing literature (A high adhesive and natural derivative chemical, Alexander asmann et al biomaterials140,2017, p115-127), then mixing 30 parts by mass of methacrylated chitosan and 300 parts by mass of methacrylated casein, adding the mixture into 1000ml of 0.01M phosphate buffer solution containing 5 parts by mass of photoinitiator LAP, stirring and dissolving at 40 ℃ to obtain a component A solution with the mass-volume concentration ratio of the dissolved methacrylated casein being 30%, and refrigerating the solution in a dark place for later use;
(2) chromium sulfate [ Cr ] is firstly2(SO4)3 12H2O)]And tyrosine according to chromium ion: tyrosine mass 1: 1 proportion, and then dissolving in 2000ml of 0.01M phosphate buffer solution to obtain a B component solution with the trivalent chromium ion content of 0.5% (w/v) for later use.
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in 100 parts by volume: 3, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of the tissue to be bonded;
(4) closing the adhesive surface coated with the AB mixed component, and irradiating with a light source with a wavelength of 410nm for 20 seconds.
Example 3
(1) Firstly, carrying out methacrylation reaction and purification on gelatin and chondroitin sulfate respectively according to a method disclosed by the existing literature (A high adhesive and natural adhesive derivative, Alexander Assmann et al biomaterials140,2017, p115-127), then mixing 5 parts by weight of methacrylated chondroitin sulfate with 200 parts by weight of methacrylated gelatin, adding the mixture into 1000ml of 0.01M phosphate buffer solution containing 2.5 parts by weight of photoinitiator 819, stirring and dissolving at 40 ℃ to obtain a component A solution with the dissolved methacrylated casein mass-volume concentration ratio of 20%, and refrigerating the solution in dark for later use;
(2) firstly, chromium sulfate [ Cr ]2(SO4)3 12H2O)]And tyrosine according to chromium ion: tyrosine mass 10: 6, and then dissolving the mixture in 4000ml of 0.01M phosphate buffer solution to obtain 0.25% (w/v) of B component solution calculated by trivalent chromium ions for later use.
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in parts by volume 50: 1, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of a tissue to be bonded;
(4) the adhesive side coated with the AB mixed component was closed and irradiated with a light source having a wavelength of 405nm for 20 seconds.
Example 4
(1) Firstly, performing methacrylation reaction and purification on gelatin and chitosan respectively according to a method disclosed by the prior document (A high adhesive and natural derivative chemical, Alexander asmann et al biomaterials140,2017, p115-127), then mixing 12 parts by mass of methacrylated chitosan and 150 parts by mass of methacrylated gelatin, adding the mixture into 1000ml of 0.01M phosphate buffer solution containing 4 parts by mass of photoinitiator LAP, stirring and dissolving at 40 ℃ to obtain a component A solution with the mass volume concentration ratio of the dissolved methacrylated casein being 15%, and refrigerating the solution in the dark for later use;
(2) chromium chloride (3 parts) and tyrosine + hydroxyproline are firstly mixed according to the ratio of chromium ions: tyrosine + hydroxyproline (2 parts +2 parts) mass ═ 3: 4, and then dissolving the mixture in 2000 parts of 0.01M phosphate buffer solution to obtain a B component solution accounting for 0.15% (w/v) of trivalent chromium ions for later use.
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively are mixed according to the volume part of 100: 1.5, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of a tissue to be bonded;
(4) closing the adhesive surface coated with the AB mixed component, and irradiating for 15 seconds with a light source with a wavelength of 408 nm.
Example 5
(1) Firstly, performing methacrylation reaction and purification on casein and hyaluronic acid respectively according to a method disclosed by the existing literature (A high adhesive and natural derivative chemical, Alexander asmann et al biomaterials140,2017, p115-127), then mixing 26 parts by mass of methacrylated hyaluronic acid and 250 parts by mass of methacrylated casein, adding the mixture into 1000ml of 0.01M phosphate buffer solution containing 4.5 parts by mass of photoinitiator, stirring and dissolving at 40 ℃ to obtain a component A solution with the mass volume concentration ratio of the dissolved methacrylated casein being 25%, and refrigerating the solution in a dark place for later use;
(2) chromium sulfate [ Cr ] is firstly2(SO4)3 12H2O)]+ chromium chloride (2 parts +2 parts) and hydroxyproline (5 parts) as per the chromium ion: hydroxyproline mass ═ 1: mixing at a ratio of 0.8, and dissolving in 2000ml of 0.01M phosphate buffer solution to obtain a B component solution with a trivalent chromium ion content of 0.2% (w/v) for use.
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in 100 parts by volume: 2.2, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of a tissue to be bonded;
(4) closing the adhesive surface coated with the AB mixture, and irradiating with a light source having a wavelength of 400nm for 30 seconds.
Example 6
(1) Firstly, performing methacrylation reaction on gelatin, casein, chitosan and chondroitin sulfate and purifying by using a method disclosed by the existing literature (A high adhesive and natural derivative chemical, Alexander Assmann et al biomaterials140,2017, p115-127), then mixing 5 parts by mass of methacrylated chitosan, 5 parts by mass of methacrylated chondroitin sulfate, 160 parts by mass of methacrylated gelatin and 120 parts by mass of methacrylated chondroitin sulfate, adding the mixture into 1000ml of 0.01M phosphate buffer solution containing 3 parts by mass of photoinitiator LAP, stirring and dissolving at 40 ℃ to obtain a component A solution with the mass-volume concentration ratio of the dissolved methacrylated gelatin to the methacrylated casein being 28%, and refrigerating the solution for standby;
(2) chromium sulfate [ Cr ] is firstly2(SO4)3 12H2O)]And hydroxylysine according to chromium ion: mass of hydroxylysine 2: 2, and then dissolving the mixture in 1600ml of 0.01M phosphate buffer solution to obtain a B component solution accounting for 0.13% (w/v) of trivalent chromium ions for later use.
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in 100 parts by volume: 2.8, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of a tissue to be bonded;
(4) closing the adhesive surface coated with the AB mixed component, and irradiating with a light source with a wavelength of 410nm for 25 seconds.
Example 7
(1) Firstly, performing methacrylation reaction and purification on gelatin and hyaluronic acid respectively according to a method disclosed by the prior document (A high adhesive and natural derivative chemical, Alexander asmann et al biomaterials140,2017, p115-127), then mixing 10 parts by mass of methacrylated hyaluronic acid and 220 parts by mass of methacrylated gelatin, adding the mixture into 1000ml of 0.01M phosphate buffer solution containing 4.8 parts by mass of photoinitiator LAP, stirring and dissolving at 40 ℃ to obtain a component A solution with the mass-volume concentration ratio of the dissolved methacrylated gelatin being 22%, and refrigerating the solution in the dark for later use;
(2) chromium sulfate [ Cr ] is firstly2(SO4)3 12H2O)]+ chromium chloride (5 parts +5 parts) and hydroxyproline as per the chromium ion: hydroxyproline mass ═ 3: 2, and then dissolving the mixture in 800ml of 0.01M phosphate buffer solution to obtain a B component solution accounting for 0.38 percent (w/v) of trivalent chromium ions for later use.
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively are mixed according to the volume part of 100: 3, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of the tissue to be bonded;
(4) the adhesive side coated with the AB mixed component was closed and irradiated with a light source having a wavelength of 405nm for 18 seconds.
Example 8
(1) Firstly, performing methacrylation reaction on gelatin, casein, hyaluronic acid and chondroitin sulfate and purifying by using a method disclosed by the existing literature (A high adhesive and natural derivative chemicals, Alexander asmann et al biomaterials140,2017, p115-127), mixing 3 parts by mass of methacrylated hyaluronic acid, 2 parts by mass of methacrylated chondroitin sulfate, 60 parts by mass of methacrylated gelatin and 60 parts by mass of methacrylated casein, adding the mixture into 1000ml of 0.01M phosphate buffer solution containing 2 parts by mass of photoinitiator LAP, stirring and dissolving at 40 ℃ to obtain a component A solution with the mass-volume concentration ratio of the dissolved methacrylated gelatin to the methacrylated casein being 12%, and refrigerating the solution for standby;
(2) chromium sulfate [ Cr ] is firstly2(SO4)3 12H2O)]+ chromium chloride (5 parts +5 parts) and tyrosine + hydroxylysine (4 parts +5 parts) as per chromium ion: mass of hydroxylysine 1: mixing at a ratio of 0.9, and dissolvingDissolving in 2100ml of 0.01M phosphate buffer solution to obtain 0.48% (w/v) of B component solution calculated by trivalent chromium ions for later use.
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in 100 parts by volume: 2, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of a tissue to be bonded;
(4) the adhesive side coated with the AB mixed component was closed and irradiated with a light source having a wavelength of 410nm for 28 seconds.
The mass volume ratio content of the methacrylated protein in the component A is 10-30%, the mass volume ratio content of the methacrylated polysaccharide is 1-10% of the mass volume ratio content of the methacrylated protein, the mass ratio content of the photoinitiator is 0.1-0.5% of the methacrylated protein, the mass volume ratio of the trivalent chromium salt in the component B calculated by chromium ions is 0.1-0.5%, the mass of the amino acid is 0.5-1 time of the chromium ions, and the mixing proportion of the A, B component is that the mass of the chromium ions in the component B is 0.01-0.05% of the mass of the methacrylated protein in the component A.
Claims (10)
1. An elastomeric tissue sealant based on natural compounds, characterized in that the elastomeric tissue sealant is comprised of A, B components, wherein the component A comprises a polymer component consisting of methacrylated protein and methacrylated polysaccharide and a photoinitiator, the component B comprises trivalent chromium salt and amino acid, the mass volume ratio content of the methacrylated protein in the component A is 10-30%, the mass volume ratio content of the methacrylated polysaccharide is 1-10% of the mass ratio content of the methacrylated protein, the mass ratio content of the photoinitiator is 0.1-0.5% of the methacrylated protein, the mass volume ratio of the trivalent chromium salt in the component B calculated by chromium ions is 0.1-0.5%, the mass of the amino acid is 0.5-1 times of the chromium ions, and the mixing ratio of the component A, B is that the mass of the chromium ions in the component B is 0.01-0.05% of the mass of the methacrylated protein in the component A.
2. The natural compound based elastomeric tissue sealant according to claim 1 wherein said methacrylated protein in the elastomeric tissue sealant is at least one of methacrylated gelatin and methacrylated casein; the methacryloylated polysaccharide is at least one of methacryloylated chondroitin sulfate, methacryloylated hyaluronic acid and methacryloylated chitosan.
3. The natural compound based elastomeric tissue sealant according to claims 1 or 2 characterized in that said amino acids in the elastomeric tissue sealant are at least one of tyrosine, hydroxyproline and hydroxylysine; the trivalent chromium salt is at least one of chromium sulfate and chromium chloride.
4. The natural compound based elastomeric tissue sealant according to claim 1 or 2 wherein the photoinitiator in the elastomeric tissue sealant is photoinitiator 819 or photoinitiator LAP.
5. The natural compound based elastomeric tissue sealant according to claim 3 wherein said photoinitiator in the elastomeric tissue sealant is photoinitiator 819 or photoinitiator LAP.
6. A process for preparing the natural compound based elastomeric tissue sealant of claim 1, the process steps and conditions of the process are as follows:
(1) firstly, carrying out methacrylation reaction on protein and polysaccharide respectively according to the prior method to prepare and purify methacrylated protein and methacrylated polysaccharide, then mixing the methacrylated polysaccharide with the mass being 1-10% of the mass of the obtained methacrylated protein, adding 0.01M phosphate buffer solution with the mass volume concentration of 0.1-0.5% of photoinitiator for dissolution, uniformly mixing the dissolved methacrylated protein with the mass volume concentration being 10-30% (w/v) to serve as a component A, and refrigerating the component A in a dark place for later use;
(2) firstly, the trivalent chromium salt and the amino acid are mixed according to the following chromium ion: mass of amino acid 1: (0.5-1), dissolving in 0.01M phosphate buffer solution, and preparing into component B solution with trivalent chromium ion mass volume ratio concentration of 0.1-0.5% for later use;
(3) 10 minutes before use, A, B components preheated to 40 ℃ respectively were mixed in 100 parts by volume: 1-3, mixing and rapidly and uniformly stirring to form an AB mixed component, and coating the AB mixed component on the surface of a tissue to be bonded;
(4) the adhesive side coated with the AB mixture was closed and irradiated with light of 400-410nm wavelength for 10-30 seconds.
7. The method of claim 6 wherein the methacrylated protein is at least one of methacrylated gelatin and methacrylated casein; the methacryloylated polysaccharide is at least one of methacryloylated chondroitin sulfate, methacryloylated hyaluronic acid and methacryloylated chitosan.
8. The method of preparing a natural compound based elastomeric tissue sealant according to claims 6 or 7 wherein the amino acid used is at least one of tyrosine, hydroxyproline, and hydroxylysine. Preferably tyrosine and hydroxyproline; the trivalent chromium salt is at least one of chromium sulfate and chromium chloride.
9. The process for the preparation of a natural compound based elastomeric tissue sealant according to claims 6 or 7, wherein the initiator used in the process is the photoinitiator 819 or the photoinitiator LAP.
10. The process for the preparation of a natural compound based elastomeric tissue sealant according to claim 8, wherein the initiator used is photoinitiator 819 or photoinitiator LAP.
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