CN110408038B - Performance-controllable shell oligosaccharide-based biological adhesive and preparation method thereof - Google Patents
Performance-controllable shell oligosaccharide-based biological adhesive and preparation method thereof Download PDFInfo
- Publication number
- CN110408038B CN110408038B CN201910681976.2A CN201910681976A CN110408038B CN 110408038 B CN110408038 B CN 110408038B CN 201910681976 A CN201910681976 A CN 201910681976A CN 110408038 B CN110408038 B CN 110408038B
- Authority
- CN
- China
- Prior art keywords
- chitosan oligosaccharide
- adhesive
- acid
- dihydroxyphenylpropionic acid
- polyethylene glycol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
Abstract
The invention provides a performance-controllable shell oligosaccharide-based biological adhesive and a preparation method thereof, belonging to the technical field of high polymer materials and biological materials. The invention takes biomacromolecule chitosan oligosaccharide as a matrix material, modifies the chitosan oligosaccharide by using 3, 4-dihydroxyphenylpropionic acid to obtain chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid modified macromolecules, and then carries out cross-linking reaction with polyethylene glycol diglycidyl ether through an amino ring-opening epoxy group to prepare the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid-polyethylene glycol diglycidyl ether biological adhesive. The adhesive material prepared by the invention has good tissue adhesion performance, higher mechanical strength, proper degradation period and no cytotoxicity, can be used for surface adhesion of various materials such as glass, metal and oxides thereof, plastics and the like, and can also be used for adhesion of animal body epidermis and internal tissue organs in the field of clinical medical surgery.
Description
Technical Field
The invention relates to a performance-controllable shell oligosaccharide-based biological adhesive and a preparation method thereof, belonging to the technical field of high polymer materials and biological materials.
Background
Today with the development of medical programs, there are about 400 million surgical operations worldwide each year and growing year by year. At present, materials such as a suture line and a rivet are mostly adopted for suturing wounds by using a surgical suture fastening technology, but secondary pain and wound infection are often caused, and tissue function recovery is even interfered. Therefore, the development of the biological adhesive capable of adhering the wound has important theoretical significance and practical application value.
In order to effectively solve the regeneration problem of the repaired defective tissue, a great deal of basic research and clinical practice are carried out by vast scholars at home and abroad, great progress is made, and the biological adhesive material is powerfully expanded in the field of tissue engineering. At present, the materials used for biological adhesives mainly include chemical species (polyurethane, cyanoacrylate and the like), degradable synthetic macromolecules (polyvinyl alcohol, polycaprolactone and the like), biological macromolecular polysaccharides (chitosan, alginic acid, hyaluronic acid and the like), and biological macromolecular polypeptides (polyglutamic acid, polylysine, fibrin and the like). Of these, the former two have high strength, but are poor in biocompatibility, bondability to surrounding tissue interfaces, and degradability. The biomacromolecule polysaccharide and the polypeptide are widely used for constructing biological adhesive materials due to the advantages of good structure adjustability, biocompatibility, degradability and the like. However, the bioadhesives currently produced are generally less viscous, making their use limited. Therefore, there is an urgent market demand for the development of a bioadhesive material having strong adhesiveness.
The catechol group is considered as a main functional group which can be adhered to the surfaces of various materials by mussels, is a strong polar group, can generate the acting forces of hydrogen bonds, covalent bonds, coordination bonds, pi-pi accumulation and the like with different materials to have strong adhesion, is easy to be oxidized to form quinone, and is further crosslinked and polymerized to form a high-strength polymer with a network structure. Meanwhile, the catechol-based compound has excellent biocompatibility, can promote the adhesion and proliferation capacity of cells, and can be kept in a mild human environment relatively stably for a long time, so that the catechol-based compound is used for modifying, degrading and synthesizing macromolecules or biological macromolecules in more researches so as to improve the adhesion strength and tissue regeneration of the modified macromolecules. Besides high adhesion strength, the biological adhesive material also has a great research focus on how to increase internal stress inside the adhesive. Most of the existing researches improve the internal stress through non-covalent bond interaction such as static electricity, and the like, but few researches improve the performance through the covalent bond interaction formed by ring-opening epoxy groups. Thus, the invention is based on a catechol-based modified biopolymer, a covalently cross-linked network being formed by opening the epoxy groups in glycidyl ethers of amino groups in the biopolymer, in order to increase the adhesive strength of the bioadhesive.
Disclosure of Invention
The invention aims to provide a preparation method of a performance-controllable shell oligosaccharide-based tissue repair adhesive, which has excellent tissue adhesion performance, higher mechanical strength, proper degradation period and no cytotoxicity, and is expected to be applied to the field of clinical medical operations as an adhesive, a sealant, a hemostatic material and the like for tissue repair.
The technical scheme of the invention is as follows: modifying chitosan oligosaccharide with 3, 4-dihydroxyl phenylpropionic acid with excellent adhesion to prepare modified macromolecular chitosan oligosaccharide-3, 4-dihydroxyl phenylpropionic acid with adhesion; and then, amino on the modified chitosan oligosaccharide-3, 4-dihydroxy phenylpropionic acid is utilized to form a covalent crosslinking network on epoxy groups on the polyethylene glycol diglycidyl ether, so as to prepare the chitosan oligosaccharide-3, 4-dihydroxy phenylpropionic acid-polyethylene glycol diglycidyl ether biological adhesive.
The method comprises the following steps:
(1) reacting 3, 4-dihydroxyphenylpropionic acid with chitosan oligosaccharide in an acidic medium (pH 4.5-6.0) for 10-15 h under the action of a catalyst to obtain modified macromolecular chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid; the reaction formula is as follows:
(2) reacting the chitosan oligosaccharide-3, 4-dihydroxyl phenylpropionic acid obtained in the step (1) with polyethylene glycol diglycidyl ether through an amino ring-opening epoxy group to obtain a chitosan oligosaccharide-based adhesive, wherein the reaction formula is as follows:
wherein a, n and m are 2-20, and n>m；
Represents a chitosan oligosaccharide sugar chain.
In one embodiment of the present invention, the molecular weight of the chitosan oligosaccharide in step (1) is 2000, and the molar ratio of the amino group on the chitosan oligosaccharide to the carboxyl group in the 3, 4-dihydroxyphenylpropionic acid is amino: the carboxyl is 5: 1-1: 1, the 3, 4-dihydroxy phenylpropionic acid in the obtained chitosan oligosaccharide-3, 4-dihydroxy phenylpropionic acid is 5-26%, namely the molar ratio of the 3, 4-dihydroxy phenylpropionic acid unit to the sugar ring unit on the single chain of the chitosan oligosaccharide is 5-26%.
In one embodiment of the invention, the catalyst is a carbodiimide and an N-hydroxysuccinimide.
In one embodiment of the invention, in the step (2), the molar ratio of the amino group in the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid to the epoxy group in the polyethylene glycol diglycidyl ether is 10:3 to 10:5, and the reaction is carried out in a thermostatic water bath at 37 ℃ for 24 hours.
In one embodiment of the invention, the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid-polyethylene glycol diglycidyl ether biological adhesive can adjust the crosslinking degree of the adhesive and realize the regulation and control of the adhesion performance by changing the conditions of the adding amount, the composition, the reaction degree of amino and epoxy, temperature, time and the like.
The invention has the advantages of
The chitosan oligosaccharide-3, 4-dihydroxy phenylpropionic acid-polyethylene glycol diglycidyl ether biological adhesive with a cross-linked structure prepared by the method has the advantages of simple and mild preparation method and controllable performance. Regulating and controlling each performance of the biological adhesive material by changing the structure and the composition of the biological adhesive material; the biological adhesive of chitosan oligosaccharide-3, 4-dihydroxy benzene propionic acid-polyethylene glycol diglycidyl ether has high adhesive strength up to 157kPa, can be used for surface adhesion of various materials such as glass, metal and oxides thereof, plastics and the like, and has potential application value in the field of clinical medical surgery.
Drawings
FIG. 1 is a UV-VIS spectrum (a) and a NMR spectrum (b) of chitooligosaccharide-3, 4-dihydroxyphenylpropionic acid
FIG. 2 shear adhesion Strength between bioadhesive Material and Pigskin tissue
Detailed Description
EXAMPLE 1 preparation of modified Macro-Chitosan oligosaccharide-3, 4-Dihydroxypropionic acid
Dissolving 0.5g (3mmol) of chitosan oligosaccharide (molecular weight 2000) in 10mL of ultrapure water acidified by hydrochloric acid, wherein the pH value is 5.5, adding 10mL of 0.284g (1.5mmol) of ethanol solution of 3, 4-dihydroxyphenylpropionic acid, adding a mixed solution of 0.622g of carbodiimide, 0.076g N-hydroxysuccinimide and 10mL of morpholine sodium ethanesulfonate buffer solution, regulating the pH value of a reaction system to be 5.5 by using 0.1mol/L of dilute hydrochloric acid, reacting at 25 ℃ for 12h under a nitrogen atmosphere, dialyzing the obtained product in deionized water for 3 days, and freeze-drying to obtain the brown cotton flower-shaped modified macromolecular chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid (CSA), wherein the access amount of the 3, 4-dihydroxyphenylpropionic acid is 26%.
Under the same conditions, when the amounts of 3, 4-dihydroxyphenylpropionic acid were replaced with 0.114g (0.6mmol), 0.142g (0.75mmol), 0.189g (1mmol), and 0.237g (1.25mmol), the access amounts of CSA to be prepared were 5%, 8%, 12%, and 18%, respectively.
The structure and the access amount of the prepared modified macromolecule are proved by ultraviolet-visible spectrum and nuclear magnetic spectrum, and are shown in figure 1.
The influence of different access amounts of chitosan oligosaccharide-3, 4-dihydroxyl phenylpropionic acid on the adhesive is explored:
selecting fresh pigskin to simulate human tissue, cutting the fresh pigskin purchased from a local market into a rectangle with uniform size, wherein the size is about 5.0cm × 1.0.0 cm, removing redundant fat on the pigskin tissue, controlling the thickness to be 1-2mm, cleaning the cut pigskin by using 0.9% sodium chloride solution, soaking the pigskin overnight by using PBS (phosphate buffer solution) with the pH value of 7.4, taking out the pigskin, and wiping the solution on the surface of the pigskin by using filter paper.
0.128g of chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid with the access amount of 0%, 5%, 8%, 12%, 18% and 26% is respectively taken as a single-component adhesive, the single-component adhesive is uniformly coated on the inner surface layer of a piece of pigskin tissue, the area is about 2.5cm × 1.0.0 cm, then the other piece of pigskin is covered and the two pieces of pigskin are pressed together, then the pigskin is placed at 37 ℃ for crosslinking and curing for 24h, a tensile test is carried out by using a universal tensile testing machine with a 10kN pressure measuring element, a sample is fixed between two clamps, the tensile rate is set to be 1mm/min, the well-bonded pigskin is taken out for a tensile shear test until the two pieces of pigskin are completely pulled apart, the maximum tensile force is the adhesive force between the adhesive and the tissue, and the results are shown in Table.
TABLE 1 adhesion Strength of Chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid with different incorporation amounts
As the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid contains a catechol group which plays a role in adhesion, the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid is used as a single-component adhesive, and the adhesion effect between CSA adhesives with different 3, 4-dihydroxyphenylpropionic acid access amounts and pigskin tissues is examined. With the increase of the 3, 4-dihydroxyphenylpropionic acid access amount, the adhesive strength between the CSA adhesive and tissues can be maximally improved to 67.5kPa, which proves that the catechol group plays a leading role in the adhesive performance and can ensure that modified macromolecules of the CSA adhesive have certain adhesiveness.
EXAMPLE 2 preparation of Chitosan oligosaccharide-3, 4-Dihydroxypropionic acid-polyethylene glycol diglycidyl ether bioadhesive
Dissolving 0.064g (4mmol) of chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid (26% of 3, 4-dihydroxyphenylpropionic acid in the example 1) in 250 mul of ultrapure water to prepare a chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid solution with the concentration of 25 wt%, adding 0.12g of polyethylene glycol diglycidyl ether (the molar ratio of amino group to epoxy group is 10:3) into the aqueous solution of the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid, magnetically stirring for 5min until the mixture is uniformly mixed, and reacting in a constant-temperature water bath at 37 ℃ for 24h to obtain the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid-polyethylene glycol diglycidyl ether biological adhesive which is marked as CSA-PEG0.30. The adhesive strength of the resulting adhesive was 110 kPa.
EXAMPLE 3 preparation of Chitosan oligosaccharide-3, 4-Dihydroxyphenylpropionic acid-polyethylene glycol diglycidyl ether bioadhesive
Referring to example 2, the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid-polyethylene glycol diglycidyl ether bioadhesive was prepared by replacing the 3, 4-dihydroxyphenylpropionic acid incorporation amount of chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid with 5% and leaving the other conditions unchanged. The adhesive strength of the resulting adhesive was 40 kPa.
EXAMPLE 4 adhesive Strength of Adhesives with different degrees of crosslinking
Referring to example 2, when the amount of polyethylene glycol diglycidyl ether was changed to 0.08g and 0.10g, respectively, under the same conditions (amino group: epoxy group molar ratios of 10:5 and 10:4, respectively), chitosan-3 was prepared with different degrees of crosslinking,4-Dihydroxyphenylpropionic acid-polyethylene glycol diglycidyl ether bioadhesive, respectively designated CSA-PEG0.20、CSA-PEG0.25。
The resulting bioadhesive was subjected to an adhesion test, as in step 2 of example 1, with the results shown in Table 2. The chitosan oligosaccharide-3, 4-dihydroxyl phenylpropionic acid and the polyethylene glycol diglycidyl ether are mixed under certain conditions, and can be crosslinked and cured to form a network structure, so that the internal stress of the network structure can be greatly improved, and the bonding strength of the biological adhesive material is improved. The result shows that the best adhesive strength of the chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid-polyethylene glycol diglycidyl ether biological adhesive can reach 157 kPa.
TABLE 2 bond strengths of adhesives with different degrees of crosslinking
In addition, the adhesive strength of the common commercialized adhesive, Fibrin glue, is 8.0KPa, and the adhesive strength of the adhesive prepared by the invention is improved by 5-20 times and is far higher than that of the commercially available Fibrin glue adhesive.
Claims (9)
1. A preparation method of a chitosan oligosaccharide-based biological adhesive is characterized in that 3, 4-dihydroxyphenylpropionic acid is used for modifying chitosan oligosaccharide to form modified macromolecular chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid, and then the modified macromolecular chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid-polyethylene glycol diglycidyl ether biological adhesive is obtained by crosslinking with polyethylene glycol diglycidyl ether.
2. The method of claim 1, wherein the molar ratio of amino groups in the chitosan oligosaccharide to carboxyl groups in the 3, 4-dihydroxyphenylpropionic acid is 5:1 to 1: 1.
3. The method of claim 1, wherein the molar ratio of the 3, 4-dihydroxyphenylpropionic acid unit in the modified macromolecular chitooligosaccharide-3, 4-dihydroxyphenylpropionic acid to the glycocyclo unit on the single chain of chitooligosaccharide is 5-26%.
4. The method of claim 1, wherein the molar ratio of amino groups in the modified macromolecular chitooligosaccharide-3, 4-dihydroxyphenylpropionic acid to epoxy groups in polyethylene glycol diglycidyl ether is 10:3 to 10: 5.
5. Method according to claim 1, characterized in that it comprises the following steps:
(1) reacting 3, 4-dihydroxy phenylpropionic acid with chitosan oligosaccharide in an acidic medium for 10-15 h under the action of a catalyst to obtain modified macromolecular chitosan oligosaccharide-3, 4-dihydroxy phenylpropionic acid;
(2) and (2) reacting the modified macromolecular chitosan oligosaccharide-3, 4-dihydroxyphenylpropionic acid obtained in the step (1) with polyethylene glycol diglycidyl ether to obtain the chitosan oligosaccharide-based adhesive.
6. The method according to claim 5, wherein the pH of the acidic medium is 4.5 to 6.0.
7. A chitooligosaccharide-based binder prepared by the method of any one of claims 1-6.
8. Use of the chito-oligosaccharide-based adhesive of claim 7 in the medical field, the use comprising: as an adhesive, sealant or hemostatic material for tissue repair.
9. Use of the chitooligosaccharide-based binder according to claim 7 for surface bonding of glass, metals and their oxides, or plastic materials.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910681976.2A CN110408038B (en) | 2019-07-26 | 2019-07-26 | Performance-controllable shell oligosaccharide-based biological adhesive and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910681976.2A CN110408038B (en) | 2019-07-26 | 2019-07-26 | Performance-controllable shell oligosaccharide-based biological adhesive and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110408038A CN110408038A (en) | 2019-11-05 |
| CN110408038B true CN110408038B (en) | 2020-07-07 |
Family
ID=68363242
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910681976.2A Active CN110408038B (en) | 2019-07-26 | 2019-07-26 | Performance-controllable shell oligosaccharide-based biological adhesive and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110408038B (en) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120328557A1 (en) * | 2011-06-23 | 2012-12-27 | Excel Med, Llc | Adhesive cell tissue gels |
| CN104013990A (en) * | 2014-06-18 | 2014-09-03 | 海南建科药业有限公司 | Modified chitosan having catechol group and biomedical material prepared from modified chitosan |
| CN104474575B (en) * | 2014-12-03 | 2017-06-30 | 广州肽莱医药科技有限公司 | Shitosan hemostatic material that covalent cross-linking is formed and preparation method thereof |
| CN107625991B (en) * | 2017-08-18 | 2020-10-23 | 中国人民解放军第四军医大学 | Preparation method of mussel-imitated functionalized fracture adhesive |
| CN109381738A (en) * | 2018-07-20 | 2019-02-26 | 中国海洋大学 | A kind of chitosan-based hydrogel and its preparation method and application |
-
2019
- 2019-07-26 CN CN201910681976.2A patent/CN110408038B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110408038A (en) | 2019-11-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107496974B (en) | Two-component medical adhesive based on glucan and chitosan and preparation method thereof | |
| CN105327388B (en) | A kind of adhesive of medical and preparation method thereof | |
| CN105477678B (en) | A kind of new bio adhesive of medical and preparation method thereof | |
| CN107469135B (en) | Heart sealing gel and preparation method thereof | |
| CN108264611A (en) | A kind of preparation method from the superpower hydrogel of adherency | |
| CN106075553A (en) | A kind of bio-medical binding agent and preparation method thereof | |
| JPWO2002096978A1 (en) | Elastin crosslinked body and method for producing the same | |
| CN105770981A (en) | Biological medical oxidative sodium carboxymethylcellulose-dopamine adhesive and preparation method thereof | |
| JP2008536958A (en) | New adhesive material, its manufacture and its application | |
| CN113512133B (en) | Preparation method of biological tissue adhesive | |
| WO2013100715A1 (en) | IN SITU CROSSLINKING HYDROGEL COMPRISING γ-POLYGLUTAMIC ACID AND METHOD FOR PRODUCING THE SAME | |
| CN113633817A (en) | In-situ polymerization strongly-adhered antibacterial hemostatic hydrogel and preparation method and application thereof | |
| CN108753202A (en) | A kind of two-component hydrogel adhesive and its preparation and application | |
| KR101804501B1 (en) | γ-Polyglutamic acid having catechol group, preparation method thereof and tissue adhesives comprising the same | |
| JP2023516335A (en) | HEMOSTATIC COVERING MATERIAL AND METHOD FOR MANUFACTURING SAME | |
| CN111635480A (en) | Anti-swelling hydrogel material and preparation method thereof | |
| CN112843325A (en) | Medical hydrogel adhesive and preparation method and application thereof | |
| CN114425103B (en) | Bionic biogel and preparation method and application thereof | |
| CN112143410B (en) | Injectable biological adhesive and preparation method and application thereof | |
| CN114272433A (en) | Gelatin-based biomedical adhesive and preparation method thereof | |
| CN110408038B (en) | Performance-controllable shell oligosaccharide-based biological adhesive and preparation method thereof | |
| CN112957518B (en) | Polysaccharide-based tissue adhesive medical adhesive and application thereof | |
| CN110694099B (en) | Mytilus edulis bionic adhesive based on polymalic acid and preparation method and application thereof | |
| CN111053946B (en) | Bi-component tissue adhesive based on polysaccharide and hyperbranched polypeptide and preparation method thereof | |
| CN113388049A (en) | Macromolecular derivative, preparation method thereof and application thereof in biological tissue adhesive |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |