CN114073787A - Biogel products for biological tissue adhesion and wound closure - Google Patents
Biogel products for biological tissue adhesion and wound closure Download PDFInfo
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- CN114073787A CN114073787A CN202010835087.XA CN202010835087A CN114073787A CN 114073787 A CN114073787 A CN 114073787A CN 202010835087 A CN202010835087 A CN 202010835087A CN 114073787 A CN114073787 A CN 114073787A
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- biological
- biogel
- tissue adhesion
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- 208000031737 Tissue Adhesions Diseases 0.000 title claims abstract description 53
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 17
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- FMJUDUJLTNVWCH-UHFFFAOYSA-N 2-ethoxy-3-(4-hydroxyphenyl)propanoic acid Chemical compound CCOC(C(O)=O)CC1=CC=C(O)C=C1 FMJUDUJLTNVWCH-UHFFFAOYSA-N 0.000 description 1
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- AYKYXWQEBUNJCN-UHFFFAOYSA-N 3-methylfuran-2,5-dione Chemical compound CC1=CC(=O)OC1=O AYKYXWQEBUNJCN-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- XLBDEMIFDOANPN-UHFFFAOYSA-N 9-benzyl-3h-purine-6-thione Chemical compound C1=NC=2C(=S)N=CNC=2N1CC1=CC=CC=C1 XLBDEMIFDOANPN-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
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- VJDDQSBNUHLBTD-GGWOSOGESA-N [(e)-but-2-enoyl] (e)-but-2-enoate Chemical compound C\C=C\C(=O)OC(=O)\C=C\C VJDDQSBNUHLBTD-GGWOSOGESA-N 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
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- ZZTCPWRAHWXWCH-UHFFFAOYSA-N diphenylmethanediamine Chemical compound C=1C=CC=CC=1C(N)(N)C1=CC=CC=C1 ZZTCPWRAHWXWCH-UHFFFAOYSA-N 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
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- 238000002955 isolation Methods 0.000 description 1
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- 239000012528 membrane Substances 0.000 description 1
- KQSABULTKYLFEV-UHFFFAOYSA-N naphthalene-1,5-diamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1N KQSABULTKYLFEV-UHFFFAOYSA-N 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
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- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229920001228 polyisocyanate Polymers 0.000 description 1
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- 241000894007 species Species 0.000 description 1
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- 229910052717 sulfur Inorganic materials 0.000 description 1
- KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 description 1
- VJDDQSBNUHLBTD-UHFFFAOYSA-N trans-crotonic acid-anhydride Natural products CC=CC(=O)OC(=O)C=CC VJDDQSBNUHLBTD-UHFFFAOYSA-N 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
Images
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- 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
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- A—HUMAN NECESSITIES
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- 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
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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
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
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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
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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
- A61L24/10—Polypeptides; Proteins
- A61L24/108—Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
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- A—HUMAN NECESSITIES
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- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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- C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
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Abstract
The invention aims to provide a biological adhesive product capable of quickly and conveniently realizing biological tissue adhesion and wound closure, which is characterized by comprising a biological adhesive layer, wherein the biological adhesive layer is in a solid film shape, contains biological macromolecules and is modified with biological adhesive groups on the surface, and the biological adhesive groups are formed by modifying the biological macromolecules by at least one of o-nitrobenzyl optical triggers and N-hydroxysuccinimide. When the biological glue product is used, the biological glue product can generate adhesive force only by being attached after being wetted so as to complete tissue adhesion or hemostasis, and does not need to be coated or solidified in advance, so that the operation is simple, and the tissue adhesion or hemostasis can be quickly and conveniently carried out.
Description
Technical Field
The invention belongs to the field of biological materials, relates to a biological adhesive used in medical treatment, and particularly relates to a biological adhesive product used for biological tissue adhesion and wound closure.
Background
In the current surgical operation, a means for closing a damaged tissue, a wound, or the like is to suture the damaged tissue, the wound, or the like with a surgical thread. However, suturing is done manually by a physician, and not only is the operation complicated and time consuming, but it is also difficult to achieve rapid closure in an emergency.
In order to achieve rapid closure of damaged tissue and wounds, bio-adhesive materials for tissue adhesion and wound closure have appeared in the prior art. For example, CN105131315A discloses a non-radical photochemical crosslinking hydrogel material, which comprises a component a containing an o-nitrobenzyl type photo-trigger modified polymer derivative and a component B containing a hydrazide, hydroxylamine or primary amine polymer derivative, wherein when in use, the component a and the component B are mixed and irradiated for 30 s-1 min to form a gel, thereby achieving wound repair or wound tissue isolation. For another example, CN108187130A discloses a reagent for repairing biological injury or stopping bleeding, which comprises a photoinitiator and natural biological macromolecules modified by photoresponsive crosslinking groups such as o-nitrobenzyl-based photo-trigger, and can be cured by several seconds of light when in use, thereby achieving rapid hemostasis.
The biological glue material is in a liquid state and can be solidified under the condition of illumination. However, because of the need for curing under light conditions, these bioceramic materials must be applied relatively uniformly to the injured site, and then light equipment must be used, and if the application is not uniform, the curing may be incomplete, which may affect the repairing effect. In addition, since these biological adhesive materials are in a liquid state, when the wound size is large, the applied adhesive cannot ensure the closing of the tissues on both sides of the wound, so that in this case, the closing must be performed in advance (for example, by performing simple suturing or using other fixing means to close and fix the tissues on both sides of the wound). Therefore, the prior art of this type of biomaterial is still inconvenient and not fast enough to be used in emergency situations when applied to damaged tissues and wound closure.
Disclosure of Invention
In order to solve the problems, the invention provides a biological adhesive product which can quickly, simply and conveniently realize biological tissue adhesion and wound closure, and adopts the following technical scheme:
the invention provides a biological adhesive product for biological tissue adhesion and wound closure, which is characterized by comprising the following components: the biological adhesive layer is in a solid film shape, contains biological macromolecules and is modified with biological adhesive groups on the surface, wherein the biological adhesive groups are formed by modifying the biological macromolecules by at least one of o-nitrobenzyl light triggers and active agents,
the active agent is any one or more of N-hydroxysuccinimide (NHS), 4-N, N-Dimethylpyridine (DMAP), 4-pyrrolidinylpyridine (4-PPY), 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt),
the structure of the o-nitrobenzyl plate photoscreening machine is shown as the following formula I or formula II:
in formula I and formula II:
LG (leaving group) is a halogen atom (including F, Cl, Br, I) or a group of the form O-R ', S-R ', NH-R ';
r' is selected from hydrogen, alkyl substituent, ether substituent, ketone substituent, ester substituent, amide substituent, thioester substituent or phosphonate substituent;
R1selected from hydrogen, halogen atoms, hydroxyl groups, mercapto groups, amine groups, nitro groups, cyano groups, aldehyde groups, ketone groups, ester groups, amide groups, phosphonic acid groups, phosphonate groups, sulfonic acid groups, sulfonate groups, sulfone groups, sulfoxide groups, aryl groups, heteroaryl groups, alkyl groups, alkylene groups, modified alkyl groups or modified alkylene groups;
R2、R3，R4，R5any one or more of them is selected from the group consisting of a terminal amine group, hydroxyl group, mercapto group, halogen, carboxyl or carboxylate group-modified aryl group, heteroaryl group, alkyl group, alkylene group, modified alkyl group or modified alkylene group, and may be freely selected from the group consisting of hydrogen, halogen atom, hydroxyl group, mercapto group, amine group, nitro group, cyano group, aldehyde group, ketone group, carboxyl group, ester group, amide group, phosphonate group, sulfonic acid groupA group, a sulfonate group, a sulfone group, a sulfoxide group, an aryl group, a heteroaryl group, an alkyl group, an alkylene group, a modified alkyl group, or a modified alkylene group.
In addition, among the various groups mentioned above, there may be further such features that:
modifying alkyl to be any carbon atom of alkyl by a halogen atom, -OH, -SH, -NO2-CN, -CHO, -COOH, carboxylate group, ester group, amide group, aryl group, arylene group, -CO-, -O-, -S-, -SO-, -2A group obtained by replacing at least one group of primary amino, secondary amino, tertiary amino, quaternary ammonium base, saturated or unsaturated monocyclic or bicyclic cycloalkylene and bridged lipid heterocycle, wherein the modified alkyl has 1 to 30 atoms, and the carbon-carbon single bond can be replaced by carbon-carbon double bond or carbon-carbon triple bond optionally;
the alkylene group being modified to have any carbon atom of the alkylene group being substituted by a halogen atom, -OH, -SH, -NO2-CN, -CHO, -COOH, ester group, amide group, aryl group, arylene group, -CO-, -O-, -S-, -SO-, -2A group obtained by replacing at least one group of primary amino, secondary amino, tertiary amino, quaternary ammonium base, saturated or unsaturated monocyclic or bicyclic cycloalkylene and bridged alicyclic ring, wherein the modified alkylene has 1 to 30 atoms, and a carbon-carbon single bond of the modified alkylene can be replaced by a carbon-carbon double bond or a carbon-carbon triple bond;
the alkyl substituent is selected from the following structures:
-(CH2)xCH3wherein x is not less than 0 and is an integer;
the ether substituents are selected from the following structures:
-(CH2CH2O)xCH3、-(CH2)x(CH2CH2O)yCH3or is
Wherein x and y are integers not less than 0;
the ketone substituent is selected from the following structures:
-CO(CH2)xCH3、-CO(CH2CH2O)xCH3、-CO(CH2)x(CH2CH2O)yCH3wherein x and y are integers not less than 0;
the ester substituent is selected from the following structures:
-COO(CH2)xCH3、-COO(CH2CH2O)xCH3、-COO(CH2)x(CH2CH2O)yCH3wherein x and y are integers not less than 0;
the amide substituent is selected from the following structures:
-CONH(CH2)xCH3、-CONH(CH2CH2O)xCH3、-CONH(CH2)x(CH2CH2O)yCH3wherein x and y are integers not less than 0;
the thioester substituent is selected from the following structures:
-COS(CH2)xCH3、-COS((CH2CH2O)xCH3、-COS(CH2)x(CH2CH2O)yCH3wherein x and y are integers not less than 0;
the phosphonate substituent is selected from the following structures: -PO (OH) O (CH)2)xCH3、--PO(OH)O(CH2CH2O)xCH3、--PO(OH)O(CH2)x(CH2CH2O)yCH3Wherein x and y are integers not less than 0;
the aryl group is a 5-10 membered aromatic monocyclic ring or aromatic condensed bicyclic ring structure;
the heteroaryl is a 5-10 membered aromatic monocyclic ring or aromatic condensed bicyclic ring structure containing at least one heteroatom selected from O, S, N or Si on the ring;
the halogen atoms are each independently selected from F, Cl, Br, I.
The biogel product for biological tissue adhesion and wound closure provided by the invention can also have the technical characteristics that the biological adhesion layer is formed by crosslinking and solidifying a solution of biological macromolecules and modifying biological adhesion groups, or is formed by removing and modifying the biological adhesion groups by a solvent. Further, the crosslinking curing may be photo-crosslinking or chemical crosslinking. Further, the photo-crosslinking process may be: modifying at least one photosensitive crosslinking group on a main chain macromolecule, dissolving the main chain macromolecule modified by the photosensitive crosslinking group in deionized water to form a solution with the mass fraction of 1-50%, then adding a photoinitiator with the mass of 0.5-5% of solute, stirring uniformly, pouring into a mold to form a liquid film with the thickness of 0.5-5 mm, and irradiating by using light with the wavelength of 300-450 nm for 1-1800 seconds until the curing is realized. Specifically, the photoinitiator may be one or more of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone, lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate, sodium phenyl (2,4, 6-trimethylbenzoyl) phosphate, and magnesium phenyl (2,4, 6-trimethylbenzoyl) phosphate. The cross-linking agent for forming the photosensitive cross-linking group can be one or more of o-nitrobenzyl type photo-trigger, maleic anhydride (also called maleic anhydride), citraconic anhydride, cis-3-carboxypentene dianhydride (cis-aconitic anhydride), 4-pentenoic anhydride, crotonic anhydride and methacrylic anhydride.
In addition, the process of crosslinking by the chemical crosslinking agent may be: dissolving biomacromolecules in a solvent to form a solution with the mass fraction of 0.5-40%, then adding a chemical cross-linking agent, stirring for 1-360 minutes, pouring into a mold to form a liquid film with the thickness of 0.5-5 mm, and standing until the liquid film is completely cured to form hydrogel. Wherein, when the biological macromolecule is a polycarboxyl compound, the chemical cross-linking agent can be a polyamino micromolecule cross-linking agent. Specifically, the polyamino small molecule cross-linking agent may be any one of linear aliphatic diamines with a carbon chain length of 2 to 10, such as ethylenediamine, 1, 4-butanediamine, diethylenetriamine, triethylenetetramine, piperazine, and the like, and isomers thereof, aromatic polyamino compounds, such as p-phenylenediamine, benzenetriamine, 1, 5-naphthalenediamine, naphthylethylenediamine, melamine, diaminodiphenylmethane, 3' -diaminobenzidine, 4' -diaminodiphenyl sulfide, 4' -diaminodiphenyl sulfone, and the like, and isomers thereof. When the biological macromolecule is a polyamino compound, the chemical cross-linking agent can be a polycarboxyl small molecule cross-linking agent or a polyaldehyde small molecule cross-linking agent. Specifically, the polycarboxy small molecule cross-linking agent can be any one of aliphatic polycarboxy compounds with carbon chain length between 2 and 10, such as oxalic acid, succinic acid, maleic acid, fumaric acid, citric acid and the like, isomers thereof and corresponding derivative acid anhydrides, aromatic polycarboxy compounds, such as terephthalic acid, trimesic acid, pyromellitic acid, 2, 6-naphthalenedicarboxylic acid, 1,4,5, 8-naphthalenedicarboxylic acid and the like, isomers thereof and corresponding derivative acid anhydrides. The multi-aldehyde micromolecule cross-linking agent can be any one of aliphatic multi-aldehyde compounds with the carbon chain length of 2-10, such as glyoxal, succinaldehyde, glutaraldehyde and the like and isomers thereof, and aromatic multi-carboxyl compounds, such as terephthalaldehyde, trimesic aldehyde, 2, 3-naphthaldehyde and the like and isomers thereof. When the biomacromolecule is a macromolecule with a main chain rich in amino groups, hydroxyl groups or sulfhydryl groups, the chemical crosslinking agent can be any one of glycidyl ether, divinyl sulfone, polyisocyanate or isocyanate-terminated polyurethane. Specifically, the glycidyl ether may be any one of ethylene glycol diglycidyl ether, glycerol triglycidyl ether, and 1, 4-butanediol diglycidyl ether (BDDE).
The biogel product for biological tissue adhesion and wound closure provided by the invention can also have the technical characteristics that the biological macromolecules are high molecular polymers, the solvent is one or a mixture of more of tetrahydrofuran, dichloromethane, trichloromethane, ethyl acetate, diethyl ether, acetone and acetonitrile, and the solvent is removed by a volatilization method.
The biogel product for biological tissue adhesion and wound closure provided by the invention can also have the technical characteristics that the biological macromolecule contains amino or hydroxyl and does not contain carboxyl, and the bioadhesive group is an o-nitrobenzyl light trigger group formed by modifying a carboxylated o-nitrobenzyl light trigger compound or an active agent o-nitrobenzyl light trigger compound.
The biogel product for biological tissue adhesion and wound closure provided by the invention can also have the technical characteristics that the biological macromolecule contains carboxyl and does not contain amino and hydroxyl, the bioadhesive group is one or a mixture of an active ester group formed by modification of an active agent and an o-nitrobenzyl light trigger group formed by modification of an aminated o-nitrobenzyl light trigger compound.
The biogel product for biological tissue adhesion and wound closure provided by the invention can also have the technical characteristics that the biological macromolecule contains carboxyl, amino and hydroxyl, the biological adhesion group is one or a mixture of more of an active ester group formed by modification of an active agent, an o-nitrobenzyl light trigger group formed by modification of an aminated o-nitrobenzyl light trigger compound and an o-nitrobenzyl light trigger group formed by modification of an active agent o-nitrobenzyl light trigger compound.
The biogel product for biological tissue adhesion and wound closure provided by the invention can also have the technical characteristics that a biological adhesive group is modified on a biological macromolecule by adopting a condensation reaction, and the condensation agent can be a carbodiimide salt condensation agent, a carbonium salt condensation agent, a chitosan derivative, a salt, a chitosan derivative, a salt, a polymer, a salt, a polymer, a salt, a polymer,
any one or more of onium salt condensing agent, organic phosphorus condensing agent, triphenylphosphine or 4- (4, 6-dimethoxytriazine-2-yl) -4-methylmorpholine hydrochloride. Specifically, the carbodiimide salt-type condensing agent may be any one of Dicyclohexylcarbodiimide (DCC), Diisopropylcarbodiimide (DIC), and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI). Carbonium salt condensing agent O- (7-azabenzotriazole-1-yl) -di (dimethylamino) carbonium Hexafluorophosphate (HATU), O- (benzotriazol-1-yl) -di (dimethylamino) carbonium Hexafluorophosphate (HBTU), O- (5-chlorobenzotriazole-1-yl) -di (dimethylamino) carbonium Hexafluorophosphate (HCTU), o- (benzotriazol-1-yl) -bis (dimethylamino) carbonium tetrafluoroborate (TBTU), O- (N-succinimidyl) -bis (dimethylamino) carbonium tetrafluoroborate (TSTU), O- (N-endo-5-norbornene-2, 3-dicarbonimide) -bis (dimethylamino) carbonium tetraborate (TNT).U).
The onium salt condensing agent may be any one of benzotriazol-1-yloxy-tris (dimethylamino) phosphonium hexafluorophosphate (BOP), benzotriazol-1-yloxy-tris (tetrahydropyrrolyl) phosphonium hexafluorophosphate (PyBOP), diphenylphosphoryl chloride (DPP-Cl), diethyl cyanophosphate (DECP), diphenyl phosphate azide (DPPA, thiodimethylphosphoryl azide (MPTA), bis (2-oxo-3-oxazolidinyl) phosphoryl chloride (BOP-Cl), the organic phosphorus condensing agent may be any one of diphenylphosphoryl chloride (DPPA-Cl), diethyl cyanophosphate (DECP), diphenyl phosphate azide (DPPA), thiodimethylphosphoryl azide (MPTA), bis (2-oxo-3-oxazolidinyl) phosphoryl chloride (BOP-Cl), preferably, the condensing agent used in the modification reaction of N-hydroxysuccinimide is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and the condensing agent used in the modification reaction of an o-nitrobenzyl photoinitiator is 4- (4, 6-dimethoxytriazin-2-yl) -4-methylmorpholine hydrochloride.
The biological adhesive product for biological tissue adhesion and wound closure provided by the invention also comprises a substrate layer attached to the biological adhesion layer. Further, the basal layer can be a membrane made of any one or more polymers of silk fibroin, collagen, hyaluronic acid, pectin, arabic gum, xanthan gum, guar gum, carrageenan, tamarind gum, seaweed gum, sesbania gum, carrageenan, agar, dextrin, sodium starch phosphate, sodium carboxymethyl starch, hydroxypropyl starch, sodium carboxymethyl cellulose, propylene glycol alginate, sodium caseinate, polyethylene glycol, polyoxyethylene polyoxypropylene block copolymer, polyvinyl alcohol, polylactic acid-glycolic acid copolymer, polycaprolactone, polyurethane and polyethyleneimine.
Action and Effect of the invention
According to the biogel product for biological tissue adhesion and wound closure, the biological adhesion layer contains biological macromolecules and is surface-modified with biological adhesion groups, the biological adhesion groups are formed by modifying the biological macromolecules by at least one of o-nitrobenzyl photo-trigger and N-hydroxysuccinimide, wherein the o-nitrobenzyl photo-trigger groups can generate free nitroso groups under the illumination condition, and the nitroso groups can be chemically bonded with sugar ring hydroxymethyl, double bonds and sulfydryl on the biological tissue so as to generate adhesion; the N-hydroxysuccinimide group can be directly chemically bonded to an amino group or a hydroxyl group on the surface of the biological tissue, thereby generating adhesion. Therefore, the surface of the biological adhesion layer can be adhered to the surface of the biological tissue through simple operations such as wetting, covering, illumination and the like, and the biological tissue closure or wound closure can be realized without smearing, namely, the tissue adhesion or hemostasis can be quickly and conveniently carried out. In addition, the biological adhesive layer is in a curing film shape, so that the biological adhesive layer has certain strength, and can close the wound while adhering to the surface of the biological tissue, so that the biological adhesive layer does not need to be closed in advance.
Drawings
FIG. 1 is a schematic structural view of a double-sided adhesive type bio-adhesive article according to the present invention;
FIG. 2 is a schematic structural view of a single-sided adhesive type bio-adhesive article of the present invention;
FIG. 3 is a photograph of a double-sided bio-adhesive article according to a first embodiment of the present invention;
FIG. 4 is a photograph of a single-sided biogel product according to example two of the present invention;
FIG. 5 is a photograph of a double-sided bio-adhesive product according to a third embodiment of the present invention;
FIG. 6 is a photograph of a single-sided biogel product according to example four of the present invention;
FIG. 7 is a graph showing the results of measuring the adhesion of a bio-adhesive product according to various embodiments of the present invention;
FIG. 8 is a photograph showing the biocompatibility test of the biogel products of the first and third embodiments of the present invention;
FIG. 9 is a photograph showing the results of the tissue adhesion test of the double-sided type bio-adhesive tape product according to the first embodiment of the present invention;
FIG. 10 is a photograph showing the results of the tissue adhesion test of the double-sided type bio-adhesive tape preparation according to the second embodiment of the present invention;
FIG. 11 is an animal experiment photograph showing the hemostatic and tissue adhesive properties of the single-sided biogel preparation of example two of the present invention.
Detailed Description
The biogel product for biological tissue adhesion and wound closure provided by the invention comprises two forms: one in the form of an adhesive article having adhesive properties on both sides (hereinafter referred to as a double-sided adhesive type); another form is a form of a glue article having adhesive properties on one side (hereinafter referred to as a one-sided glue type).
Fig. 1 is a schematic structural view of a double-sided adhesive type bio-adhesive product of the present invention, and fig. 2 is a schematic structural view of a single-sided adhesive type bio-adhesive product of the present invention.
As shown in fig. 1 and 2, the double-sided adhesive type bio-adhesive product of the present invention comprises a bio-adhesive layer, and both surfaces of the bio-adhesive layer have bio-adhesive groups; the single-sided biogel product comprises a biogel adhesion layer and a substrate layer attached to the biogel adhesion layer, wherein the surface of the biogel adhesion layer, which is opposite to the substrate layer, is provided with a bioadhesion group.
The following describes embodiments of the present invention with reference to the drawings. The reagents used in the following examples are commercially available and the experimental procedures and experimental conditions not specified are those conventional in the art.
In the following examples, for the sake of simplicity of explanation, N-hydroxysuccinimide is replaced by its abbreviation "NHS", o-nitrobenzyl-type photo-trigger by its abbreviation "NB", lithium phenyl (2,4, 6-trimethylbenzoyl) phosphate by its abbreviation "LAP", 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride by its abbreviation "EDC", and 4- (4, 6-dimethoxytriazin-2-yl) -4-methylmorpholine hydrochloride by its abbreviation DMTMM.
< example one >
This example provides a double-sided adhesive type bioadhesive article comprised of a hydrogel type bioadhesive layer having bioadhesive groups on both surfaces.
The preparation method of the biogel product in the embodiment comprises the following steps: dissolving Hyaluronic Acid (HA) in water to prepare a 4% aqueous solution, adding 1, 4-butanediol diglycidyl ether (BDDE) with a molar ratio of 1:10, quickly stirring for 1 minute, pouring into a mold to form a liquid film with the thickness of 5mm, and standing until the liquid film is completely cured to form a hydrogel-like HA hydrogel layer. And soaking the obtained HA hydrogel layer into an aqueous solution containing excessive EDC/NHS, then adding non-excessive amination NB for reacting for half an hour, then washing with deionized water, and drying in a vacuum drying oven for 12 hours to obtain the biological glue product of the embodiment.
The biogel product obtained by the process is composed of a bioadhesive layer, wherein the main component of the bioadhesive layer is HA modified by NHS and NB.
HA is a natural biological macromolecule, which itself HAs carboxyl groups. In the above treatment process, HA is cured to form hydrogel by a chemical cross-linking agent BDDE, and after the cured HA hydrogel is put into an excessive EDC/NHS aqueous solution, NHS is reacted with carboxyl on the HA molecular main chain, so that NHS is modified on the HA molecular main chain. Since HA is reacted in EDC/NHS aqueous solution after curing, the modification reaction of NHS mainly occurs at the surface of the hydrogel, i.e., the surface of the hydrogel layer is made to have NHS groups. Then, when a non-excess amount of aminated NB is added for reaction, the aminated NB reacts with NHS partially modified on the surface of HA, so that the molecular backbone of HA is modified with NB groups. Thus, the modified HA of this example acts as a bioadhesive macromolecule with both surfaces bearing both NB and NHS groups.
Fig. 3 is a photograph of a double-sided bio-adhesive product according to a first embodiment of the present invention.
As shown in fig. 3, the mold used in this example was a circular petri dish, and thus the resulting double-sided bio-gel product was circular and had an appearance of a cured transparent hydrogel film.
< example two >
This example provides a single-sided adhesive type bio-adhesive product formed by attaching a base layer to the double-sided adhesive type bio-adhesive product of the first example.
The preparation process of the single-sided adhesive type bio-adhesive product of the embodiment is as follows:
referring to the preparation of the double-sided adhesive type bio-adhesive product of example one, the HA hydrogel layer was prepared. Then, after adding non-excessive amination NB for reaction for half an hour and cleaning, the mixture is not dried, but is placed into a container paved with a silk fibroin film, the two layers of films are arranged to be attached, and then the two layers of films are placed into a vacuum drying oven to be dried for 12 hours, so that the single-sided adhesive type biological adhesive product of the embodiment is obtained. The single-sided adhesive type biological adhesive product consists of a biological adhesive layer and a substrate layer, wherein one surface of the single-sided adhesive type biological adhesive product is a biological adhesive layer surface and is provided with NB and HNS; the other surface is the basal layer surface, and has no bioadhesive groups such as NB or NHS.
FIG. 4 is a photograph of a single-sided biogel product according to example two of the present invention.
As shown in fig. 4, the mold used in this example was the same as in the first example, and the container on which the silk fibroin film was spread was also a round petri dish, so that the obtained single-sided bio-gel product was round and had an appearance of a cured transparent hydrogel film.
< example three >
This example provides a double-sided adhesive type bioadhesive article comprised of a polymeric bioadhesive layer having bioadhesive groups on both surfaces.
The preparation method of the biogel product in the embodiment comprises the following steps: dissolving poly-L-lactic acid (PLLA) in chloroform to form a solution with the mass fraction of 10%, pouring the solution into a mould to form a liquid film with the thickness of 0.5mm, putting the mould into a vacuum drying oven to volatilize and remove the chloroform, and obtaining the PLLA polymer layer. The resulting PLLA polymer layer was soaked in an aqueous solution containing an excess of DMTMM and an excess of aminated NB was added for 1 hour. And then, washing with deionized water, and drying in a vacuum drying oven for 2 hours to obtain the biological glue product of the embodiment.
The biological adhesive product obtained by the process is composed of a biological adhesive layer, wherein the main component of the biological adhesive layer is PLLA modified by NB. PLLA is a polymer macromolecule, having a carboxyl group, capable of reacting with aminated NB to modify the carboxyl group with NB.
Because the added amination NB is excessive, the main chain of PLLA at the surface of the adhesive layer is fully modified with NB which is taken as a bioadhesive macromolecule and contains NB groups; accordingly, both surfaces of the double-sided bio-adhesive product of the present embodiment have NB.
Fig. 5 is a photograph of a double-sided bio-adhesive product according to a third embodiment of the present invention.
As shown in fig. 5, the mold used in this example is a circular petri dish, and thus the obtained double-sided bio-adhesive product is circular and has an appearance of a cured transparent adhesive film.
< example four >
This example provides a single-sided adhesive type bio-adhesive product, which is formed by attaching a base layer to the double-sided adhesive type bio-adhesive product of the third example.
The preparation process of the single-sided adhesive type bio-adhesive product of the embodiment is as follows:
referring to example three, a PLLA polymer layer was first prepared. Then, after adding excessive aminated NB for reaction for half an hour and washing, the mixture is not dried, but placed in a container paved with a polyethylene glycol film, the two layers of films are arranged to be attached, and then the mixture is placed in a vacuum drying oven to be dried for 2 hours, so that the single-sided adhesive type biological adhesive product of the embodiment is obtained. The single-sided adhesive type biological adhesive product consists of a biological adhesive layer and a substrate layer, wherein one surface of the single-sided adhesive type biological adhesive product is the surface of the biological adhesive layer and is provided with an NB group; the other surface is the base layer surface and has no NB.
FIG. 6 is a photograph of a single-sided biogel product according to example four of the present invention.
As shown in fig. 6, the mold and the container used in this example were circular petri dishes, and thus the obtained single-sided bio-gel product was circular and had an appearance of a cured transparent adhesive film.
< example five >
This example provides a double-sided adhesive type bioadhesive article comprised of a hydrogel type bioadhesive layer having bioadhesive groups on both surfaces.
The preparation method of the biogel product in the embodiment comprises the following steps: dissolving methacrylic anhydride modified hyaluronic acid (HAMA) and LAP in water to obtain water solution with HAMA mass fraction of 4% and LAP mass fraction of 0.08%, stirring for 10 min, pouring into a mold to form a liquid film with thickness of 2mm, and processing with a wavelength of 365nm and light intensity of 60mW/cm2The resulting solution was irradiated with light for 60 seconds to obtain a photocrosslinked HAMA hydrogel layer. And soaking the HAMA hydrogel layer into an aqueous solution containing excessive EDC/NHS for reaction for half an hour, washing with deionized water, and drying in a vacuum drying oven for 6 hours to obtain the biological glue product of the embodiment.
The biogel product obtained by the process is composed of a bioadhesive layer, wherein the main components of the bioadhesive layer are HAMA with NHS modification: the methacrylic anhydride groups contained in HAMA are capable of crosslinking under the conditions of light and the presence of an initiator to cure the HAMA to a gel, forming a photocrosslinked HAMA hydrogel layer. Then, in the EDC/NHS solution, NHS reacts with carboxyl in HAMA in the presence of EDC, so that NHS groups are modified on HAMA.
Thus, HAMA with NHS modification of this example, as a bioadhesive macromolecule, contains NHS groups; accordingly, both surfaces of the double-sided bio-adhesive article of the present embodiment have NHS. The appearance of the double-sided bio-gel product obtained in this example was similar to that of the example, and was in the form of a cured transparent hydrogel film.
< example six >
This example provides a single-sided adhesive type bio-adhesive product formed by attaching a base layer to the double-sided adhesive type bio-adhesive product of the fifth example.
The preparation process of the single-sided adhesive type bio-adhesive product of the embodiment is as follows:
referring to the preparation of the double-sided adhesive type bio-adhesive product of the fifth embodiment, the photo-crosslinked HAMA hydrogel layer is prepared, then the HAMA hydrogel layer is soaked in the aqueous solution containing excessive EDC/NHS to react for half an hour, and after being washed by deionized water, the mixture is not dried, but placed in a container paved with a silk fibroin film, and the two layers of films are arranged to be attached, and then the mixture is placed in a vacuum drying oven to be dried for 12 hours, so that the single-sided adhesive type bio-adhesive product of the present embodiment is obtained. The single-sided adhesive type biological adhesive product consists of a biological adhesive layer and a substrate layer, wherein one surface of the single-sided adhesive type biological adhesive product is a biological adhesive layer surface and is provided with biological adhesive groups such as NHS; the other surface is the basal layer surface and has no NHS. The appearance of the single-sided bio-gel product obtained in this example was in the form of a cured transparent hydrogel film, similar to that of example two.
< example seven >
This example uses the Burstpressure method to test the wet surface adhesion of the biogel articles prepared in each of the above examples. During testing, the biogel products of the examples were subjected to three treatments, namely: wetting with water, irradiating, wetting with an aqueous solution containing initiator LAP, irradiating, and testing the wet surface adhesion, wherein the test process comprises the following steps:
(1) the double-coated adhesive type bio-adhesive article of example one was wetted with deionized water and tested for wet surface adhesion, resulting in 330mmHg, which was recorded as dHA-NB-NHS group.
(2) The double-sided adhesive type bio-adhesive product of example one was wetted with deionized water and applied with a wavelength of 395nm and a light intensity of 60mW/cm2After 5 seconds of light irradiation, the wet surface adhesion was tested at 450mmHg and reported as dHA-NB-NHS + UV group.
(3) The double-sided adhesive type biogel product of example one was wetted with a deionized water solution containing initiator LAP and treated with 395nm wavelength and 60mW/cm light intensity2After 5 seconds of light irradiation, the wet surface adhesion was measured to be 650mmHg and is reported as dHA-NB-NHS + UV/LAP.
(4) The single-sided adhesive type bio-gel product of example two was wetted with deionized water and tested for wet surface adhesion of 330mmHg, which was assigned as sHA-NB-NHS group.
(5) The single-sided adhesive type bio-adhesive product of example two was wetted with deionized water and applied with a wavelength of 395nm and a light intensity of 60mW/cm2After 5 seconds of light irradiation, the wet surface adhesion was tested at 450mmHg and is assigned as sHA-NB-NHS + UV group.
(6) The single-sided adhesive type biogel product of example two was wetted with a deionized water solution containing initiator LAP and treated with 395nm wavelength and 60mW/cm light intensity2After 5 seconds of light irradiation, the wet surface adhesion was measured to be 650mmHg and is assigned as sHA-NB-NHS + UV/LAP group.
(7) The double-sided adhesive type bio-gel product of example three was wetted with deionized water and tested for wet surface adhesion and found to be 0mmHg, which was recorded as the dPLLA-NB group.
(8) The double-sided adhesive type bio-adhesive product of example III was wetted with deionized water and applied with a wavelength of 395nm and a light intensity of 60mW/cm2After 5 seconds of light irradiation, the wet surface adhesion was tested at 280mmHg and reported as dPLLA-NB + UV.
(9) The double-sided adhesive type biogel product of example III was wetted with a deionized water solution containing initiator LAP and treated with 395nm wavelength and 60mW/cm light intensity2After 5 seconds of light irradiation, the wet surface adhesion was tested at 370mmHg and reported as dPLLA-NB + LAP/UV.
(10) The single-sided adhesive type bio-adhesive article of example four was wetted with deionized water and tested for wet surface adhesion of 0mmHg and assigned as sPLLA-NB.
(11) The single-sided adhesive type bio-adhesive product of example four was wetted with deionized water and applied with a wavelength of 395nm and a light intensity of 60mW/cm2After 5 seconds of light irradiation, the wet surface adhesion was tested at 280mmHg and is reported as sPLLA-NB + UV.
(12) The single-sided adhesive type biogel product of example four was wetted with a deionized water solution containing initiator LAP and treated with 395nm wavelength and 60mW/cm light intensity2After 5 seconds of light irradiation, the wet surface adhesion was tested at 370mmHg and is reported as sPLLA-NB + UV/LAP.
(13) The double-sided adhesive type bio-gel product of example five was wetted with deionized water and tested for wet surface adhesion, resulting in 330mmHg, which was assigned to the dHA-NHS group.
(14) The two-sided adhesive type bio-adhesive product of example V was wetted with deionized water and applied with a wavelength of 395nm and a light intensity of 60mW/cm2After 5 seconds of light irradiation, the wet surface adhesion was tested at 330mmHg and reported as dHA-NHS + UV group.
(15) The double-sided adhesive type biogel preparation of example five was wetted with a deionized water solution containing initiator LAP and treated with 395nm wavelength and 60mW/cm light intensity2After 5 seconds of light irradiation, the wet surface adhesion was measured to be 330mmHg and is reported as dHA-NHS + UV/LAP.
(16) The single-sided adhesive type bio-gel product of example six was wetted with deionized water and tested for wet surface adhesion of 330mmHg, which was assigned as sHA-NHS group.
(17) The single-sided adhesive type bio-adhesive product of example six was wetted with deionized water and applied with a wavelength of 395nm and a light intensity of 60mW/cm2After 5 seconds of light irradiation, the wet surface adhesion was tested at 330mmHg and reported as sHA-NHS + UV group.
(18) The single-sided adhesive type biogel product of example six was wetted with a deionized water solution containing initiator LAP and treated with 395nm wavelength and 60mW/cm light intensity2After 5 seconds of light irradiation, the wet surface adhesion was measured to be 330mmHg and is assigned as sHA-NHS + UV/LAP group.
FIG. 7 is a graph showing the results of measuring the adhesion of the biogel product according to the embodiments of the present invention.
As shown in fig. 7, the biogel products of the first and second examples show wet tissue adhesion after being wetted with deionized water, and the wet tissue adhesion is sequentially enhanced after being wetted with deionized water and illuminated, and wetted with LAP solution and illuminated; the biogel products of the third and fourth examples do not exhibit wet tissue adhesion after being wetted with deionized water, exhibit wet tissue adhesion after being wetted with deionized water and illuminated, and further enhance wet tissue adhesion after being wetted with LAP solution and illuminated; the biogel products of the fifth and the sixth examples show wet-side tissue adhesion in three different treatment modes of deionized water wetting, deionized water wetting and illumination and LAP solution wetting and illumination, but the wet-side tissue adhesion in the three cases is not different.
By analysis, the principle is as follows: the surface of the biogel product of the first and second examples contains two kinds of bioadhesive groups, namely NB and NHS. The NHS can be directly chemically bonded with amino or hydroxyl on the surface of the biological tissue to generate adhesion, so that deionized water is adopted for wetting, and certain wet-surface tissue adhesion is achieved; NB can generate aldehyde group under the condition of illumination and can be chemically bonded with amino on the surface of biological tissue so as to generate adhesion; in the presence of an initiator, nitroso generated by NB illumination can be chemically bonded with sugar ring hydroxymethyl, double bond, sulfydryl and the like on biological tissues under the action of free radicals, so that the adhesion is further enhanced.
The surface of the biogel product in the third and fourth embodiments contains a bioadhesive group NB, wherein the NB can generate aldehyde groups under the illumination condition and can be chemically bonded with amino groups on the surface of biological tissues so as to generate adhesion; in the presence of an initiator, nitroso generated by NB illumination can be chemically bonded with sugar ring hydroxymethyl, double bond, sulfydryl and the like on biological tissues under the action of free radicals, so that the adhesion is enhanced.
In the fifth and sixth examples, the surface of the biogel product contains a bioadhesive group, NHS, which can be directly chemically bonded with the amino group on the surface of the biological tissue to generate adhesion, and the chemical bonding reaction is not affected by light or an initiator, so that the same wet-side tissue adhesion is shown in all three different treatment modes.
< example eight >
This example is a biocompatibility test of the biogel product of the present invention. In this example, the biocompatibility of the bio-gel product of the first and third examples was verified by cell experiments.
The specific operation is as follows:
(1) culturing the human mesenchymal stem cells on the surface of the single-sided biological glue product in the first example for 5 days, and observing the growth condition of the cells, wherein the cells are well spread in the first day of planting;
(2) l929 cells were cultured on the surface of the single-sided type biogel preparation of example III for 7 days, and the cell growth effect was examined by the method of CCK-8.
Fig. 8 is a photograph showing the biocompatibility test of the bio-gel product according to the first and third embodiments of the present invention. Fig. 8(a) is a photograph showing an experiment of the bio-gel product according to the first embodiment, and fig. 8(b) is a photograph showing an experiment of the bio-gel product according to the third embodiment.
As shown in fig. 8(a), the human mesenchymal stem cells were cultured on the surface of the single-sided type bio-gel product of the first example for 5 days, and the cells were significantly proliferated in the 5 days, which indicates that the bio-gel product of the first example has good biocompatibility.
As shown in fig. 8(b), the L929 cell species were cultured on the surface of the single-sided type bio-gel product of example three for 7 days, and the number of cells was significantly increased in the 7 days, indicating that the cells can proliferate, and the bio-gel product of example three had good biocompatibility.
< example nine >
This example is an animal experiment showing the hemostatic and tissue adhesive properties of the biogel product of the present invention. In this example, the hemostasis performance and tissue adhesion performance of the biogel products of each example were verified through experiments, specifically as follows.
(1) Single-sided biogel preparation of example one
The double-sided bio-adhesive product of example one was wetted with deionized water, and then directly attached between two pieces of meat, and the adhesion effect was observed.
Fig. 9 is a photograph showing the tissue adhesion performance test of the double-sided bio-adhesive product according to the first embodiment of the present invention.
As shown in fig. 9, after being attached between two pieces of meat, the double-sided bio-adhesive product of example one can firmly adhere the two pieces of meat together, and even if one piece of meat is sandwiched, the other piece of meat can remain adhered without falling off, indicating that the double-sided bio-adhesive product has good tissue adhesion performance.
(2) Single-sided biogel preparation of example two
The single-sided biogel product of example two was wetted with a deionized water solution containing initiator LAP, pressed onto the surface of a piece of meat and illuminated with 395nm light at 60mW/cm2Was irradiated for 5 seconds, and adhesion was observed.
Fig. 10 is a photograph showing the tissue adhesion performance test of the double-sided bio-adhesive tape product according to the second embodiment of the present invention.
As shown in fig. 10, the single-sided bio-gel product of the second example was attached to the meat piece and irradiated with light, and then the meat was firmly adhered to the gel surface, and the meat piece was not dropped even if only the gel portion was sandwiched, indicating that the single-sided bio-gel product had good tissue adhesion properties. In addition, even if only the part of the colloid is clamped, other colloids are not broken or torn, which shows that the single-sided biological glue product also has good mechanical strength and is not easy to break or tear in the using process to influence the tissue adhesion effect.
A heart is manufactured by a needle with the diameter of 2mm in the left ventricle of the rabbit to make ventricular penetrating injury, and the ejection of blood columns is observed; immediately thereafter, the single-sided biogel preparation of example two, which was wetted with a solution containing a LAP initiator, was pressed to the lesion and irradiated for 5 seconds.
FIG. 11 is an animal experiment photograph showing the hemostatic and tissue adhesive properties of the single-sided biogel preparation of example two of the present invention. Wherein, the left side photo is before the biological glue product is used, and the right side photo is after the biological glue product is used.
As shown in FIG. 11, the single-sided bio-gel product of example two was firmly adhered to the surface of the heart without any blood flow, demonstrating good tissue adhesion and hemostatic properties of the single-sided gel.
(3) EXAMPLE four Single-sided Bioglue preparation
A heart is manufactured by a needle with the diameter of 2mm in the left ventricle of the rabbit to make ventricular penetrating injury, and the ejection of blood columns is observed; immediately thereafter, the single-sided bio-gel product of example four was pressed to the lesion and irradiated with light for 30 seconds. After the single-sided bio-gel product of example six was used, it was firmly adhered to the surface of the heart without bleeding, demonstrating good tissue adhesion and hemostatic properties of the single-sided gel.
(4) EXAMPLE six Single-sided Bioglue preparation
A heart is manufactured by a needle with the diameter of 2mm in the left ventricle of the rabbit to make ventricular penetrating injury, and the ejection of blood columns is observed; immediately thereafter, the one-sided type bio-gel product of example six was pressed to the lesion and kept for 10 seconds. After the single-sided bio-gel product of example six was used, it was firmly adhered to the surface of the heart without bleeding, demonstrating good tissue adhesion and hemostatic properties of the single-sided gel.
In addition, the present example also performed the tissue adhesion performance and hemostasis performance tests on the single-sided bio-adhesive products or double-sided bio-adhesive products of several other examples of the present invention, which all showed similar results to the above bio-adhesive products, and the adhesion performance was substantially identical to the wet-side tissue adhesion shown in fig. 9.
That is, for the biogel product with the surface modified by NHS, the biogel product can be attached to the tissue needing to be repaired and stanched only by being wetted by deionized water, and tissue adhesion or hemostasis can be realized after pressing; for the biogel product with the NB modification on the surface, the biogel product is used by being wetted by a solution containing a photoinitiator, and then pressed onto the surface of a tissue and illuminated. In addition, for the bio-gel product with both NB and NHS modification, the attachment can be performed and tissue adhesion or hemostasis can be achieved only after being wetted with deionized water, but the adhesion can be stronger if being wetted with a solution containing a photoinitiator and being irradiated with light.
The foregoing detailed description of the preferred embodiments of the invention has been presented. It should be understood that numerous modifications and variations could be devised by those skilled in the art in light of the present teachings without departing from the inventive concepts. Therefore, the technical solutions available to those skilled in the art through logic analysis, reasoning and limited experiments based on the prior art according to the concept of the present invention should be within the scope of protection defined by the claims.
Claims (10)
1. A biogel article for biological tissue adhesion and wound closure, comprising:
the biological adhesive layer is in a solidified film shape, contains biological macromolecules, and is modified with biological adhesive groups on the surface,
wherein the bioadhesive group is formed by modifying the biopolymer with at least one of an ortho-nitrobenzyl-based photoinitiator and an active agent,
the active agent is any one or more of N-hydroxysuccinimide, 4-N, N-lutidine, 4-pyrrolidinyl pyridine, 1-hydroxybenzotriazole and 1-hydroxy-7-azabenzotriazole,
the structure of the o-nitrobenzyl plate photoscreening machine is shown as the following formula I or formula II:
in formula I and formula II:
LG is a halogen atom or a group of the form O-R ', S-R ', NH-R ';
r' is selected from hydrogen, alkyl substituent, ether substituent, ketone substituent, ester substituent, amide substituent, thioester substituent or phosphonate substituent;
R1selected from hydrogen, halogen atoms, hydroxyl groups, mercapto groups, amine groups, nitro groups, cyano groups, aldehyde groups, ketone groups, ester groups, amide groups, phosphonic acid groups, phosphonate groups, sulfonic acid groups, sulfonate groups, sulfone groups, sulfoxide groups, aryl groups, heteroaryl groups, alkyl groups, alkylene groups, modified alkyl groups or modified alkylene groups;
R2、R3，R4，R5any one or more of them is selected from a terminal amine group, hydroxyl group, mercapto group, halogen, carboxyl or carboxylate group-modified aryl group, heteroaryl group, alkyl group, alkylene group, modified alkyl group or modified alkylene group, and may be freely selected from hydrogen, halogen atom, hydroxyl group, mercapto group, amine group, nitro group, cyano group, aldehyde group, ketone group, carboxyl group, ester group, amide group, phosphonate group, sulfonic acid group, sulfonate group, sulfone group, sulfoxide group, aryl group, heteroaryl group, alkyl group, alkylene group, modified alkyl group or modified alkylene group.
2. The biogel article for biological tissue adhesion and wound closure according to claim 1, wherein:
wherein the bioadhesive layer is formed from a solution of the biomacromolecule cross-linked to cure and modify the bioadhesive group, or from a solution of the biomacromolecule solvent removed and modified the bioadhesive group.
3. The biogel article for biological tissue adhesion and wound closure according to claim 2, wherein:
wherein the crosslinking curing comprises photocrosslinking and chemical crosslinking.
4. The biogel article for biological tissue adhesion and wound closure according to claim 2, wherein:
wherein the biological macromolecule is a high molecular polymer,
the solvent is one or a mixture of more of tetrahydrofuran, dichloromethane, trichloromethane, ethyl acetate, diethyl ether, acetone and acetonitrile, and the solvent is removed by a volatilization method.
5. The biogel article for biological tissue adhesion and wound closure according to claim 1, wherein:
wherein the biological macromolecule contains amino or hydroxyl,
the bioadhesion group is an o-nitrobenzyl light trigger group formed by modifying a carboxylated o-nitrobenzyl light trigger compound or an active agent o-nitrobenzyl light trigger compound.
6. The biogel article for biological tissue adhesion and wound closure according to claim 1, wherein:
wherein the biological macromolecule contains carboxyl,
the bioadhesive group is one or the mixture of an active ester group formed by modifying an active agent and an ortho-nitrobenzyl light trigger group formed by modifying an aminated ortho-nitrobenzyl light trigger compound.
7. The biogel article for biological tissue adhesion and wound closure according to claim 1, wherein:
wherein the biological macromolecule contains carboxyl, amino and hydroxyl,
the bioadhesion group is one or a mixture of more of an active ester group formed by modifying an active agent, an o-nitrobenzyl light trigger group formed by modifying an aminated o-nitrobenzyl light trigger compound and an o-nitrobenzyl light trigger group formed by modifying an active agent o-nitrobenzyl light trigger compound.
8. The biogel article for biological tissue adhesion and wound closure according to any one of claims 1 to 7, wherein:
wherein the bioadhesive group is modified to the biopolymer using a condensation reaction,
the condensing agent used in the modification reaction of the active agent is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride,
the condensing agent used in the modification reaction of the o-nitrobenzyl light trigger is 4- (4, 6-dimethoxytriazin-2-yl) -4-methylmorpholine hydrochloride.
9. The biogel article for biological tissue adhesion and wound closure according to any one of claims 1 to 7, further comprising:
a base layer attached to the bioadhesive layer.
10. The biogel article for biological tissue adhesion and wound closure according to claim 9, wherein:
the basal layer is a film made of any one or more polymers of silk fibroin, collagen, hyaluronic acid, pectin, Arabic gum, xanthan gum, guar gum, carrageenan, tamarind gum, seaweed gum, sesbania gum, carrageenan, agar, dextrin, sodium starch phosphate, sodium carboxymethyl starch, hydroxypropyl starch, sodium carboxymethyl cellulose, propylene glycol alginate, sodium caseinate, polyethylene glycol, polyoxyethylene polyoxypropylene block copolymer, polyvinyl alcohol, polylactic acid-glycolic acid copolymer, polycaprolactone, polyurethane and polyethyleneimine.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115177779A (en) * | 2022-06-14 | 2022-10-14 | 深圳凡旻生物科技有限公司 | Biological glue and preparation method and application thereof |
| CN115192779A (en) * | 2022-08-26 | 2022-10-18 | 南京工业大学 | Preparation method of Pluronic F127/hyaluronic acid composite hydrogel biological ink |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5853744A (en) * | 1996-08-20 | 1998-12-29 | Regents Of The University Of Minnesota | Solid-phase method for attaching a biomolecule to a substrate surface with a photoreactive crosslinking agent |
| US20030035786A1 (en) * | 1999-11-04 | 2003-02-20 | Medtronic, Inc. | Biological tissue adhesives, articles, and methods |
| US20040121939A1 (en) * | 2002-12-19 | 2004-06-24 | Zanini Diana | Biomedical devices with peptide containing coatings |
| US20090081797A1 (en) * | 2007-08-31 | 2009-03-26 | Andrei G Fadeev | Reactive surface on a polymeric substrate |
| CN105131315A (en) * | 2014-11-27 | 2015-12-09 | 华东理工大学 | Non-radical photochemical crosslinked hydrogel material preparation method, product and application |
| CN108187130A (en) * | 2017-09-15 | 2018-06-22 | 浙江大学 | A kind of reagent and its application for being used for biological damage reparation or hemostasis |
| US20200171200A1 (en) * | 2016-02-08 | 2020-06-04 | The Johns Hopkins University | Dendrimer-bioadhesive polymer hydrogel nanoglue and use thereof |
-
2020
- 2020-08-19 CN CN202010835087.XA patent/CN114073787A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5853744A (en) * | 1996-08-20 | 1998-12-29 | Regents Of The University Of Minnesota | Solid-phase method for attaching a biomolecule to a substrate surface with a photoreactive crosslinking agent |
| US20030035786A1 (en) * | 1999-11-04 | 2003-02-20 | Medtronic, Inc. | Biological tissue adhesives, articles, and methods |
| US20040121939A1 (en) * | 2002-12-19 | 2004-06-24 | Zanini Diana | Biomedical devices with peptide containing coatings |
| US20090081797A1 (en) * | 2007-08-31 | 2009-03-26 | Andrei G Fadeev | Reactive surface on a polymeric substrate |
| CN105131315A (en) * | 2014-11-27 | 2015-12-09 | 华东理工大学 | Non-radical photochemical crosslinked hydrogel material preparation method, product and application |
| US20200171200A1 (en) * | 2016-02-08 | 2020-06-04 | The Johns Hopkins University | Dendrimer-bioadhesive polymer hydrogel nanoglue and use thereof |
| CN108187130A (en) * | 2017-09-15 | 2018-06-22 | 浙江大学 | A kind of reagent and its application for being used for biological damage reparation or hemostasis |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115177779A (en) * | 2022-06-14 | 2022-10-14 | 深圳凡旻生物科技有限公司 | Biological glue and preparation method and application thereof |
| CN115177779B (en) * | 2022-06-14 | 2023-12-05 | 深圳凡旻生物科技有限公司 | Biological glue and preparation method and application thereof |
| CN115192779A (en) * | 2022-08-26 | 2022-10-18 | 南京工业大学 | Preparation method of Pluronic F127/hyaluronic acid composite hydrogel biological ink |
| CN115192779B (en) * | 2022-08-26 | 2023-09-15 | 南京工业大学 | Preparation method of Pluronic F127/hyaluronic acid composite hydrogel bio-ink |
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