CN106957424A - A kind of adhesive of medical of the polymer containing catechol and preparation method thereof - Google Patents
A kind of adhesive of medical of the polymer containing catechol and preparation method thereof Download PDFInfo
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- CN106957424A CN106957424A CN201710103136.9A CN201710103136A CN106957424A CN 106957424 A CN106957424 A CN 106957424A CN 201710103136 A CN201710103136 A CN 201710103136A CN 106957424 A CN106957424 A CN 106957424A
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- Prior art keywords
- adhesive
- medical
- catechol
- polymer containing
- polymer
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- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 title claims abstract description 80
- 229920000642 polymer Polymers 0.000 title claims abstract description 63
- 230000001070 adhesive effect Effects 0.000 title claims abstract description 56
- 239000000853 adhesive Substances 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000002245 particle Substances 0.000 claims abstract description 24
- 229910004298 SiO 2 Inorganic materials 0.000 claims abstract description 17
- 239000007800 oxidant agent Substances 0.000 claims abstract description 12
- 230000001590 oxidative effect Effects 0.000 claims abstract description 8
- 125000001302 tertiary amino group Chemical group 0.000 claims abstract description 8
- 230000003993 interaction Effects 0.000 claims abstract description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- 239000000178 monomer Substances 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 11
- 230000009977 dual effect Effects 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 8
- -1 chloropropyl alcohol Chemical compound 0.000 claims description 8
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 7
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003999 initiator Substances 0.000 claims description 4
- 239000000377 silicon dioxide Substances 0.000 claims description 4
- 229940099500 cystamine Drugs 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000012535 impurity Substances 0.000 claims description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 3
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical class CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 claims description 2
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 claims description 2
- 102000008946 Fibrinogen Human genes 0.000 claims description 2
- 108010049003 Fibrinogen Proteins 0.000 claims description 2
- 229920006322 acrylamide copolymer Polymers 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 150000004292 cyclic ethers Chemical class 0.000 claims description 2
- 229940012952 fibrinogen Drugs 0.000 claims description 2
- 230000008014 freezing Effects 0.000 claims description 2
- 238000007710 freezing Methods 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 150000003553 thiiranes Chemical class 0.000 claims description 2
- 238000002604 ultrasonography Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000011630 iodine Substances 0.000 claims 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 abstract description 7
- 238000006731 degradation reaction Methods 0.000 abstract description 7
- 238000007142 ring opening reaction Methods 0.000 abstract description 4
- 230000029663 wound healing Effects 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000012567 medical material Substances 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 230000035484 reaction time Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000004132 cross linking Methods 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- FSSPGSAQUIYDCN-UHFFFAOYSA-N 1,3-Propane sultone Chemical compound O=S1(=O)CCCO1 FSSPGSAQUIYDCN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 description 2
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 2
- AWMVMTVKBNGEAK-UHFFFAOYSA-N Styrene oxide Chemical compound C1OC1C1=CC=CC=C1 AWMVMTVKBNGEAK-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- HNNQYHFROJDYHQ-UHFFFAOYSA-N 3-(4-ethylcyclohexyl)propanoic acid 3-(3-ethylcyclopentyl)propanoic acid Chemical compound CCC1CCC(CCC(O)=O)C1.CCC1CCC(CCC(O)=O)CC1 HNNQYHFROJDYHQ-UHFFFAOYSA-N 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
- VYFYYTLLBUKUHU-UHFFFAOYSA-N Dopamine Natural products NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- 229910003978 SiClx Inorganic materials 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 206010048031 Wound dehiscence Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical class CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000005543 nano-size silicon particle Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000003106 tissue adhesive Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
Classifications
-
- 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
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
-
- 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
- A61L24/0042—Materials resorbable by the body
-
- 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
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J11/00—Features of adhesives not provided for in group C09J9/00, e.g. additives
- C09J11/02—Non-macromolecular additives
- C09J11/04—Non-macromolecular additives inorganic
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J179/00—Adhesives based on macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing nitrogen, with or without oxygen, or carbon only, not provided for in groups C09J161/00 - C09J177/00
- C09J179/02—Polyamines
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/34—Silicon-containing compounds
- C08K3/36—Silica
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Inorganic Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Adhesives Or Adhesive Processes (AREA)
Abstract
The invention belongs to biology medical material technical field, a kind of adhesive of medical of polymer containing catechol is disclosed.The present invention carry out ring-opening reaction on the catechol polymer of tertiary amine group by having on main chain, so that different structure, the side chain of different grafting rates are grafted on main polymer chain prepares improved polymer containing catechol, then the polymer and the interaction of nano SiO 2 particle and oxidant are prepared into adhesive of medical.Preferably, adhesion strength and degradation property are adjustable, and bio-toxicity is low, can effectively facilitate wound healing for the adhesive of medical adhesive property that the present invention is prepared；And synthesis and preparation process is simple, with good application prospect.
Description
Technical field
The invention belongs to biology medical material technical field, in particular it relates to which a kind of polymer containing catechol is medical
Adhesive and preparation method thereof.
Background technology
" adhesive of medical " represents to include the medical supplies of adhesive plaster, styptic and surgical adhesive in a broad sense, narrow
Represent to be directly used in justice to include the adhesive of dermatology, gastroenterology, vascular surgery and orthopedic medical field.Doctor
Have the advantages that not causing secondary injury, leakage that is simple and efficient to handle, can effectively preventing gas or body fluid with adhesive, it faces
It is more and more extensive that bed application becomes.Because adhesive of medical directly contacts skin, it may be that bio-compatible, adhesive and its drop
Solving product should not be poisonous or harmful to body, i.e., with biocompatibility.In addition, even in the environment of it there is moisture its
Preferable adhesive effect should be shown, and the healing of body should not be hindered.
The adhesive of medical of current Clinical practice is mainly α-cyanoacrylatealkyl and Fibrin Glue.The former has
The advantage that adhesion strength is high, crosslinking time is short, but its catabolite has tissue toxicity.Although Fibrin Glue is from human body
Or animal body extraction, with preferable biocompatibility, but extraction cost is high, adhesion strength is low, at present can not be in clinic
Large-scale use.
The patent of the present inventor's early stage application（Application number：CN201510403167.7）Disclose a kind of poly- containing catechol
Compound, with good tissue adhesion performance, can be used to prepare medical adhesive.But the polymer exist degradation rate it is slow,
The problems such as viscosity is difficult to regulation, it is impossible to meet the requirement of adhesive of medical, be unfavorable for the healing of wound.
The content of the invention
The technical problems to be solved by the invention are the defect and deficiency for overcoming adhesive of medical in the prior art, to early stage
Synthesis be improved containing catechol polymer, then prepare a kind of adhesion organization's effect preferably, adhesion strength can adjust,
Bio-toxicity is low, degradation rate is preferable, can effectively facilitate the adhesive of medical of wound healing.
It is an object of the invention to provide a kind of adhesive of medical of polymer containing catechol.
It is a further object of the present invention to provide the preparation method of above-mentioned adhesive of medical.
The above-mentioned purpose of the present invention is that used following technical scheme gives realization：
A kind of improved polymer containing catechol, it is characterised in that its general structure such as formula（）Or formula（）It is shown：
；
；
Wherein, R is the carbochain or-CH of the length of C1~62CH2S-SCH2CH2-, R ' and R " they are hydrogen or hydroxyl, and R ' ' ' is the third naphthenic acid
Base, 1- phenylethanols base or chloropropyl alcohol base；M represents the number of repeat unit of graft side chain, and n-m represents the repetition without graft side chain
Unit number.
A kind of adhesive of medical of polymer containing catechol, is by above-mentioned improved polymer containing catechol, dioxy
What SiClx nano particle and oxidant interaction were prepared.
The present invention carries out ring-opening reaction by there is the catechol polymer of tertiary amine group on main chain.It is anti-by open loop
Should, different structure, the side chain of different grafting rates are grafted on main polymer chain, so as to control the water solubility of polymer and prepare viscous
The crosslink density of polymer during mixture.If polymer hydrophilicity is stronger, the adhesive of medical of preparation can be adsorbed in use
Substantial amounts of moisture, although degradation rate is improved, but its adhesion strength can reduce；If polymer hydrophilicity is weaker, though bond
Intensity is improved, and is but unfavorable for the biodegradation of polymer, and the adhesive of medical of preparation may hinder wound normally to heal again.
Preferably, the structural formula of the improved polymer containing catechol such as formula（）, formula（）Or formula（）It is shown：
；
Or
。
The preparation method of above-mentioned adhesive of medical, it is characterised in that comprise the following steps：
S1. the polymer containing catechol, cyclic monomer and initiator that have tertiary amine group on main chain are dissolved in organic solvent, surpassed
Sound extremely dissolves complete, 40~50 DEG C of 5~70h of reaction, and reaction product is concentrated, removed after impurity again through dialysing, freezing, is changed
The polymer containing catechol entered；
S2. improved polymer containing catechol is dissolved in organic solvent, adds ultrasound after nano SiO 2 particle and mix, system
Obtain component A；
S3. component A and B component are mixed, prepares adhesive of medical；The B component is aqueous oxidizing agent solution；
Wherein, the polymer containing catechol for having tertiary amine group described in step S1 on main chain is dopamine-N, N'- di-2-ethylhexylphosphine oxide third
Acrylamide copolymer, 6- hydroxyl dopamines -1,6 hexanediol diacrylate copolymer or 1- (3,4- dihydroxyphenyls) -2- amino
Double (propylene acyl) the cystamine copolymers of ethanol-N, N'-（Its preparation method is with reference to the present inventor's early stage patent application：
CN201510403167.7）.There is tertiary amine in the main polymer chain, without introducing tertiary amine group by side chain, can directly exist
Ring-opening reaction is carried out on main chain.
Cyclic monomer described in step S1 is cyclic ethers, cyclosiloxane or episulfide.
Preferably, cyclic monomer described in step S1 is propane sultone, styrene oxide or epoxychloropropane.
In order to control grafting rate of the cyclic monomer on main polymer chain, the throwing of polymer and cyclic monomer can be accordingly controlled
Material mole when reaction time, generally, within the specific limits, the cyclic monomer molar fraction of addition is bigger, reaction when
Between it is longer, grafting rate is higher.
Preferably, polymer and cyclic monomer described in step S1, according to catechol repeat unit：Cyclic monomer=1：0.5
~5 mol ratio is reacted, and reaction temperature is 45 DEG C, and the reaction time is 10~40h.
Preferably, initiator described in step S1 is sodium bromide, lithium bromide, hydrochloric acid, sodium methoxide, alchlor or potassium hydroxide
In one or more.
Preferably, organic solvent described in step S1 be dimethyl sulfoxide (DMSO), DMF, ethanol, pure water or N,
One or more in N- dimethylacetylamides.
Preferably, the method that impurity is removed described in step S1 is the precipitation method.
It is highly preferred that the precipitating reagent that uses of the precipitation method is tetrahydrofuran, pure water, ethanol, one kind or many in methanol
Kind.
Preferably, improved polymer containing catechol described in step S2 is dissolved in after organic solvent, resulting polymers solution
Concentration be 300~1000 mg/mL.
The nano SiO 2 particle that the present invention is used as reversible crosslink point, can improve the adhesive property of adhesive.It is excellent
Selection of land, nano SiO 2 particle particle diameter described in step S2 is 15~1000 nm, and silica quality fraction is 0~10 %.
It is highly preferred that the nano SiO 2 particle particle diameter is 30~500 nm, silica quality fraction is 1~6
%。
Preferably, ultrasonic time described in step S2 is 10~30 min, and resulting polymers solution concentration is 300~1000
mg/mL。
Preferably, ultrasonic time described in S3 is 3~10 min.
Preferably, oxidant described in step S3 is one kind in ferric trichloride, sodium metaperiodate, hydrogen peroxide, fibrinogen.
Preferably, the concentration of aqueous oxidizing agent solution described in step S3 is 8~80 mg/mL.
To a certain extent, the crosslinking points between polymer increase, polymer cohesive force increase, so as to improve adhesion strength.
When the degree of cross linking is smaller, the bonding maximum, force of adhesive is insufficiently resistant to the localised tension of wound, is easily caused wound dehiscence.Hand over
When connection spends big, the radical amount that can be acted on polymer with skin surface is strongly reduced, and adhesive hardness increases, and equally leads
The decline of adhesion strength is caused, and is unfavorable for wound healing.
Preferably, in the adhesive of medical system that control is finally mixed, the mol ratio of catechol group and oxidant is
10：1~5, to realize the ideal degree of cross linking.
Preferably, mix to be mixed A, B component by the way of dual barrel syringe is extruded in equal volume described in step S3
Close, the component of subject adhesives two can be better achieved and is well mixed.
Compared with prior art, the invention has the advantages that：
（1）Preferably, adhesion strength is good, and bio-toxicity is low for the adhesive of medical adhesion organization effect that the present invention is prepared, degraded
Speed is moderate, can effectively facilitate wound healing.
（2）The present invention carries out ring-opening reaction using the tertiary amine on main polymer chain, without introducing side chain reaction site, synthesis
And preparation technology is simple.
（3）The present invention utilizes the preferable adhesive property of catechol group and the good degradability of polymer chain and biofacies
Capacitive, the degree of cross linking is adjusted by nano SiO 2 particle, and polymer grafting rate regulation degradation rate obtains adhesion strength adjustable
Section, the good adhesive of medical of bio-compatible.
Brief description of the drawings
Fig. 1 is the degradation curve figure of the different made adhesive of medical of polymer of grafting rate.
Influences of the Fig. 2 for different-grain diameter and the nano SiO 2 particle of content to adhesion strength.
Embodiment
The present invention is made with reference to Figure of description and specific embodiment and further being elaborated, the embodiment
It is served only for explaining the present invention, is not intended to limit the scope of the present invention.Test method used in following embodiments is such as without spy
Different explanation, is conventional method；Used material, reagent etc., are the reagent commercially obtained unless otherwise specified
And material.
Embodiment 1
1st, prepare：
（1）1.0 g dopamines-N, N'- methylene-bisacrylamides are weighed, 1.2 g propane sultones, 0.2 g sodium bromides are dissolved in
10 mL N,N-dimethylformamides（The mol ratio of catechol repeat unit and cyclic monomer is 1：3）, ultrasonic 20 min obtains
To settled solution, in reacting 20 h at 45 DEG C.After the completion of reaction, gained mixed system is concentrated by vacuum distillation, so
Precipitated 2 times in tetrahydrofuran afterwards and remove unreacted propane sultone, with transfer after DMF dissolving precipitation
Dialysed 2 days for 4 DEG C into bag filter, freeze, obtain improved polymer containing catechol, its structural formula is as follows：
（2）Weigh improved polymer containing catechol obtained by 17 mg（Catechol unit concentration is 2.6 mol/L）It is dissolved in 20
μ L dimethyl sulfoxide (DMSO)s, ultrasonic 20 min adds the 500 nm silica dioxide granules that mass fraction is 1%, and ultrasonic 10 min makes system
It is well mixed, in the A cylinders for sucking dual barrel syringe.Prepare 83.3 mg/mL FeCl3The aqueous solution（Catechol group and oxidation
The mol ratio of agent is 10：2）, 20 μ L are drawn into the B cylinders of dual barrel syringe.A, B liquid in isometric extrusion dual barrel syringe,
Adhesive of medical 1 is made.
2nd, mtt assay measurement result is shown, the cell survival rate of adhesive of medical 1 is 100%.
Shown according to international ASTM standard F2255-05 measurement results, the adhesion strength of adhesive of medical 1 is 5.7kPa.
Prepare a kind of adhesive of medical without nano SiO 2 particle again by the same terms simultaneously, measure its bonding
Intensity is 3.6kPa.
Embodiment 2
1st, prepare
（1）Weigh 1.0 g 6- hydroxyl dopamine -1,6- hexanediyl ester copolymers, 0.6 g styrene oxides, 0.1
G lithium bromides are dissolved in 10 mL DMAC N,N' dimethyl acetamides（The mol ratio of catechol repeat unit and cyclic monomer is 1：2）, surpass
The min of sound 20 obtains settled solution, in reacting 35 h at 45 DEG C.After the completion of reaction, gained mixed system is passed through into vacuum distillation
Concentrated, then precipitate 2 times in ethanol and remove unreacted lithium bromide, with after DMA dissolving precipitation turns
Move on in bag filter 4 DEG C to dialyse 2 days, freeze, obtain improved polymer containing catechol, its structural formula is as follows：
（2）Weigh improved polymer containing catechol obtained by 21mg（Catechol unit concentration is 2.6 mol/L）It is dissolved in 20
μ L DMAs, ultrasonic 20 min adds the 30 nm silica dioxide granules that mass fraction is 2%, ultrasonic 10 min
It is well mixed system, in the A cylinders for sucking dual barrel syringe.Prepare the 167 mg/mL sodium metaperiodate aqueous solution（Catechol base
Group is 10 with the mol ratio of oxidant：3）, 20 μ L are drawn into the B cylinders of dual barrel syringe.In isometric extrusion dual barrel syringe
A, B liquid, be made adhesive of medical 2.
2nd, mtt assay measurement result is shown, the cell survival rate of adhesive of medical 2 is 100%.
Shown according to international ASTM standard F2255-05 measurement results, the adhesion strength of adhesive of medical 2 is 6.2kPa.
Prepare a kind of adhesive of medical without nano SiO 2 particle again by the same terms simultaneously, measure its bonding
Intensity is 4.3kPa.
Embodiment 3
1st, prepare
（1）Weigh double (propylene acyl) the cystamine copolymers of 1.0 g 1- (3,4- dihydroxyphenyl) -2- ethylaminoethanols-N, N'-, 0.2 g
Epoxychloropropane, 0.5 mL hydrochloric acid is dissolved in 10 mL DMFs/water 1：1 mixed solvent（Catechol repeats single
Member is 1 with the mol ratio of cyclic monomer：1）, ultrasonic 20 min obtains settled solution, in reacting 15 h at 45 DEG C.Reaction is completed
Afterwards, gained mixed system is concentrated by vacuum distillation, dialysis is transferred to after being precipitated with DMF dissolving
Dialysed 2 days for 4 DEG C in bag, freeze, obtain improved polymer containing catechol, its structural formula is as follows：
（2）Weigh improved polymer containing catechol obtained by 23mg（Catechol unit concentration is 2.6 mol/L）It is dissolved in 20
μ L dimethyl sulfoxide (DMSO)s, ultrasonic 20 min adds the 300 nm silica dioxide granules that mass fraction is 4%, and ultrasonic 10 min makes system
It is well mixed, in the A cylinders for sucking dual barrel syringe.Prepare the 55.6 mg/mL sodium metaperiodate aqueous solution（Catechol group and oxygen
The mol ratio of agent is 10：1）, 20 μ L are drawn into the B cylinders of dual barrel syringe.A, B in isometric extrusion dual barrel syringe
Liquid, is made adhesive of medical 3.
2nd, mtt assay measurement result is shown, the cell survival rate of adhesive of medical 3 is 100%.
Shown according to international ASTM standard F2255-05 measurement results, the adhesion strength of adhesive of medical 3 is 5.8kPa.
Prepare a kind of adhesive of medical without nano SiO 2 particle again by the same terms simultaneously, measure its bonding
Intensity is 5.4kPa.
Influence of the reaction time of embodiment 4 to polymer open loop efficiency
1st, the present embodiment is substantially same as Example 1, and the mol ratio of catechol repeat unit and cyclic monomer is 1：1, DOPA
Amine-N, N'- methylene-bisacrylamide, propane sultone, the reaction time of sodium bromide are arranged to 10h, 20h, 30h, 40h, grind
Study carefully influence of the reaction time to polymer grafting rate.
2nd, as shown in table 1, within the specific limits, with the growth in reaction time, the grafting rate of polymer constantly increases result
It is high.
Influence of the reaction time of table 1 to DCP-SB open loop efficiency
| Sequence number | Reaction time（h） | Grafting rate（%） |
| 1 | 10 | 11 |
| 2 | 20 | 15 |
| 3 | 30 | 18 |
| 4 | 40 | 21 |
The depolymerization performance of embodiment 5 is tested
1st, 4 kinds of polymer of different grafting rates and non-grafted dopamine-N, N'- methylene-bisacrylamide in Example 4,
200mg polymer is taken respectively in the centrifuge tube weighed, and adds 5mL PBS cushioning liquid（PH=7.4,37 DEG C of temperature）, wait to gather
Compound is not swum in after the water surface, and centrifuge tube is immersed into the PBS cushioning liquid of 37 DEG C of temperature control.After a period of time, take out from
Heart pipe outwells cushioning liquid, and polymer is rinsed repeatedly with deionized water, lyophilized to weigh, and calculates weight difference before and after degraded, Mei Geju
Compound parallel determination 3 times.
2nd, result is as shown in Figure 1：Compared with non-grafted dopamine-N, N'- methylene-bisacrylamide, with grafting
The raising of rate, the degradation rate of polymer gradually increases.
Influence of the nano SiO 2 particle of embodiment 6 to adhesives intensity
1st, the present embodiment is substantially same as Example 1, and it is 15nm, 30nm, 300nm, 500nm and 2 μm of titanium dioxide to choose particle diameter
Nano silicon particles are added in polymer by 1%, 2%, 4%, 6% content, the silica nanometer of research different-grain diameter and content
Influence of the particle to adhesive of medical adhesion strength.
2nd, result is as shown in Fig. 2 the influence difference of different-grain diameter and the nano SiO 2 particle of content to adhesion strength
Significantly, when the content of nano SiO 2 particle is 2%, in addition to 2 μm of particle diameters, the adhesion strength of other particle diameters all reaches
It is maximum.It can be seen that, in certain limit, with the increase of nano SiO 2 particle addition, the adhesion strength of adhesive of medical
In increase.
Claims (10)
1. a kind of improved polymer containing catechol, it is characterised in that its general structure such as formula（）Or formula（）It is shown：
Wherein, R is selected from the carbochain or-CH of the length of C1 ~ 62CH2S-SCH2CH2-, R ' is selected from hydrogen atom or hydroxyl, and R " is selected from hydrogen atom
Or hydroxyl, R ' ' ' is propane sulfonic acid base, 1- phenylethanols base or chloropropyl alcohol base, and m represents the number of repeat unit of graft side chain, n-m tables
Show the number of repeat unit without graft side chain.
2. the adhesive of medical of a kind of polymer containing catechol, it is characterised in that be as improved containing neighbour described in claim 1
What benzenediol polymer, nano SiO 2 particle and oxidant interaction were prepared.
3. adhesive of medical according to claim 2, it is characterised in that the knot of the improved polymer containing catechol
Structure formula such as formula（）, formula（）Or formula（）It is shown：
4. the preparation method of the adhesive of medical described in Claims 2 or 3, it is characterised in that comprise the following steps：
S1. the polymer containing catechol, cyclic monomer and initiator that have tertiary amine group on main chain are dissolved in organic solvent, surpassed
Sound extremely dissolves complete, 40~50 DEG C of 5~70h of reaction, and reaction product is concentrated, removed after impurity again through dialysing, freezing, is changed
The polymer containing catechol entered；
S2. improved polymer containing catechol is dissolved in organic solvent, adds ultrasound after nano SiO 2 particle and mix, system
Obtain component A；
S3. component A and B component are mixed, prepares adhesive of medical；The B component is aqueous oxidizing agent solution；
Wherein, the polymer containing catechol for having tertiary amine group described in step S1 on main chain is dopamine-N, N'- di-2-ethylhexylphosphine oxide third
Acrylamide copolymer, 6- hydroxyl dopamines -1,6 hexanediol diacrylate copolymer or 1- (3,4- dihydroxyphenyls) -2- amino
Double (propylene acyl) the cystamine copolymers of ethanol-N, N'-；
Cyclic monomer described in step S1 is cyclic ethers, cyclosiloxane or episulfide.
5. preparation method according to claim 4, it is characterised in that polymer and cyclic monomer described in step S1, according to
Catechol repeat unit：Cyclic monomer=1：0.5~5 mol ratio is reacted.
6. preparation method according to claim 4, it is characterised in that initiator described in step S1 be sodium bromide, lithium bromide,
One or more in hydrochloric acid, sodium methoxide, alchlor or potassium hydroxide.
7. preparation method according to claim 4, it is characterised in that nano SiO 2 particle particle diameter is described in step S2
15~1000 nm, silica quality fraction is 0.1~10 %.
8. preparation method according to claim 4, it is characterised in that oxidant described in step S3 is ferric trichloride, high iodine
One kind in sour sodium, hydrogen peroxide, fibrinogen, the concentration of aqueous oxidizing agent solution is 8~80 mg/mL.
9. preparation method according to claim 4, it is characterised in that in the adhesive of medical system that control finally gives,
The mol ratio of catechol group and oxidant is 10：1~5.
10. preparation method according to claim 4, it is characterised in that mix to use dual barrel syringe described in step S3
The mode extruded in equal volume is mixed A, B component.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112310403A (en) * | 2021-01-04 | 2021-02-02 | 清陶（昆山）能源发展有限公司 | Silicon-based negative electrode of lithium ion battery and preparation method and application thereof |
| CN115337470A (en) * | 2022-07-20 | 2022-11-15 | 淮阴工学院 | Preparation method of endothelial cell-friendly intimal hyperplasia resistant coating layer |
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| US5606012A (en) * | 1992-04-21 | 1997-02-25 | Societa' Consortile Ricerche Angelini S.P.A. | Polyetheramidoamine hydrogels as heparinizable materials |
| CN104623725A (en) * | 2014-12-31 | 2015-05-20 | 深圳清华大学研究院 | Bioadhesive and preparation method thereof |
| CN105017528A (en) * | 2015-07-10 | 2015-11-04 | 中山大学 | Preparation method and application of catechol-containing polymer |
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Patent Citations (4)
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| US3853804A (en) * | 1970-08-14 | 1974-12-10 | California Inst Of Techn | Ionic block elastomeric polymers |
| US5606012A (en) * | 1992-04-21 | 1997-02-25 | Societa' Consortile Ricerche Angelini S.P.A. | Polyetheramidoamine hydrogels as heparinizable materials |
| CN104623725A (en) * | 2014-12-31 | 2015-05-20 | 深圳清华大学研究院 | Bioadhesive and preparation method thereof |
| CN105017528A (en) * | 2015-07-10 | 2015-11-04 | 中山大学 | Preparation method and application of catechol-containing polymer |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112310403A (en) * | 2021-01-04 | 2021-02-02 | 清陶（昆山）能源发展有限公司 | Silicon-based negative electrode of lithium ion battery and preparation method and application thereof |
| CN112310403B (en) * | 2021-01-04 | 2021-04-06 | 清陶（昆山）能源发展有限公司 | Silicon-based negative electrode of lithium ion battery and preparation method and application thereof |
| CN115337470A (en) * | 2022-07-20 | 2022-11-15 | 淮阴工学院 | Preparation method of endothelial cell-friendly intimal hyperplasia resistant coating layer |
| CN115337470B (en) * | 2022-07-20 | 2023-06-30 | 淮阴工学院 | Preparation method of endothelial cell friendly type intimal hyperplasia resistant coating layer |
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