CN115040699A - Heat-cured sodium hyaluronate coating, medical catheter and instrument - Google Patents
Heat-cured sodium hyaluronate coating, medical catheter and instrument Download PDFInfo
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- CN115040699A CN115040699A CN202110255509.0A CN202110255509A CN115040699A CN 115040699 A CN115040699 A CN 115040699A CN 202110255509 A CN202110255509 A CN 202110255509A CN 115040699 A CN115040699 A CN 115040699A
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- China
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- cross
- linking agent
- coating
- sodium hyaluronate
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- 238000000576 coating method Methods 0.000 title claims abstract description 76
- 239000011248 coating agent Substances 0.000 title claims abstract description 72
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical compound [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 title claims abstract description 31
- 229920002385 Sodium hyaluronate Polymers 0.000 title claims abstract description 30
- 229940010747 sodium hyaluronate Drugs 0.000 title claims abstract description 30
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 75
- 239000000463 material Substances 0.000 claims abstract description 27
- 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 group 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 abstract description 14
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 14
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 14
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000126 substance Substances 0.000 claims abstract description 9
- 229920001187 thermosetting polymer Polymers 0.000 claims abstract description 4
- 229920000642 polymer Polymers 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 238000004132 cross linking Methods 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- VPKDCDLSJZCGKE-UHFFFAOYSA-N carbodiimide group Chemical group N=C=N VPKDCDLSJZCGKE-UHFFFAOYSA-N 0.000 claims description 6
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims description 5
- 239000012948 isocyanate Substances 0.000 claims description 5
- 150000002513 isocyanates Chemical class 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 2
- 230000001680 brushing effect Effects 0.000 claims description 2
- 238000007598 dipping method Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229920000058 polyacrylate Polymers 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 239000004814 polyurethane Substances 0.000 claims description 2
- 229920002635 polyurethane Polymers 0.000 claims description 2
- 125000005373 siloxane group Chemical group [SiH2](O*)* 0.000 claims description 2
- 238000005507 spraying Methods 0.000 claims description 2
- 229920006158 high molecular weight polymer Polymers 0.000 claims 1
- 231100000419 toxicity Toxicity 0.000 abstract description 9
- 230000001988 toxicity Effects 0.000 abstract description 9
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 239000000839 emulsion Substances 0.000 abstract description 2
- 230000005012 migration Effects 0.000 abstract description 2
- 238000013508 migration Methods 0.000 abstract description 2
- 238000001556 precipitation Methods 0.000 abstract description 2
- 239000002861 polymer material Substances 0.000 abstract 1
- 238000007711 solidification Methods 0.000 abstract 1
- 230000008023 solidification Effects 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 66
- -1 siloxane structure Chemical group 0.000 description 27
- 230000001050 lubricating effect Effects 0.000 description 16
- 238000012360 testing method Methods 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000004971 Cross linker Substances 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 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 description 5
- 229920002614 Polyether block amide Polymers 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 125000005916 2-methylpentyl group Chemical group 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000005057 Hexamethylene diisocyanate Substances 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000008199 coating composition Substances 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate group Chemical group [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical compound [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003764 2,4-dimethylpentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004337 3-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
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- 239000006185 dispersion Substances 0.000 description 1
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- 230000000694 effects Effects 0.000 description 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 229920002521 macromolecule Polymers 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- CSJDCSCTVDEHRN-UHFFFAOYSA-N methane;molecular oxygen Chemical compound C.O=O CSJDCSCTVDEHRN-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 238000002324 minimally invasive surgery Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
-
- 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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
-
- 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
-
- 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/06—Coatings containing a mixture of two or more compounds
-
- 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/08—Coatings comprising two or more layers
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a thermosetting sodium hyaluronate coating, which comprises a top layer, a bottom layer and a cross-linking agent, wherein the main material of the top layer is hyaluronic acid or sodium hyaluronate, the main material of the bottom layer is a water-based high polymer material, the cross-linking agent is a multifunctional molecule, the cross-linking agent comprises a hydrophilic end and a hydrophobic end, and the cross-linking agent is respectively cross-linked with the top layer and the bottom layer through the hydrophilic end and the hydrophobic end. A medical catheter and apparatus are also disclosed. According to the invention, the biological toxicity generated by migration and precipitation of small molecular substances after solidification is reduced by selecting the aqueous high-molecular emulsion in the bottom layer, and the pollution of an organic solvent to the environment and operators is reduced; the cross-linking agent molecules are covalently bonded with the top layer and the bottom layer simultaneously, so that the hydrophilic coating has good firmness, lubricity and biocompatibility.
Description
Technical Field
The invention belongs to the field of medical biological coatings, and particularly relates to a cross-linking agent for a hydrophilic coating of a catheter, a thermosetting sodium hyaluronate coating and a medical appliance comprising the same.
Background
With the continuous development of science and technology, new and effective treatment means are continuously presented in the medical field, minimally invasive surgery is a more clinical treatment mode, and correspondingly, minimally invasive surgical instruments for intervention or natural cavities and canals are also greatly developed, such as catheters, catheters for cardiovascular and cerebrovascular diseases, prosthesis conveyors, artificial lens conveyors, various calculus minimally invasive surgical instruments and the like. When in operation, because of the factors such as roughness or edges and corners of the surface of the surgical instruments, and the like, and the surgical instruments enter the human body and are in contact with blood vessels, tissues or organs, the body is damaged; in practice, in order to reduce the trauma to the human body caused by the surgical instruments introduced into the human body and to improve the manipulability of the surgeon, it is generally necessary to coat the surfaces of the surgical instruments with a lubricant. The traditional method is to coat a layer of lubricating substance, such as silicone oil, glycerin and the like, on the surface of a surgical instrument before operation, but the coating is easy to fall off and cannot keep the lubricity of the surgical instrument in the whole process of entering, operating, removing and the like.
At present, available lubricating coatings on the market have good lubricating property, but the lubricating coatings have poor firmness, are easy to fall off from base materials such as instruments and the like, and are difficult to maintain continuous lubricating property. WO2006056482A1 uses PVP as a lubricating component, the grafting reaction of active sites of an active substance is initiated by UV photons, the coating can only be applied to surfaces irradiated by UV, such as the outer wall of a pipeline, the inner wall cannot be cured due to the non-irradiation of the UV, the water absorbability of the PVP is not good as that of sodium hyaluronate, so the lubricity of the coated instrument is not good as that of the sodium hyaluronate when in use, the coating formula of WO9938545A1 contains a large amount of small molecule components and organic solvents in the bottom layer and the top layer, a part of the crosslinked small molecules are easy to migrate to the surface of the coating after curing to be separated out, toxicity is caused to human bodies, the organic solvents are harmful to operators and the environment due to volatilization in the coating process, the crosslinking agent of WO9938545A1 contains double bonds and isocyanate functional groups, the double bonds UV or ebeam are needed to initiate polymerization crosslinking, the isocyanate has high activity and can be cured and crosslinked at normal temperature or under heating but has high toxicity, easily causes more side reactions and easily causes yellowing of the coating.
Disclosure of Invention
The first purpose of the invention is to provide a heat-cured sodium hyaluronate coating, wherein a cross-linking agent is of an amphiphilic structure, and a bottom layer substance physically adsorbed or chemically bonded on a substrate and hyaluronic acid (sodium) on a top layer are connected in a covalent bond grafting mode of the cross-linking agent to form a hydrophilic lubricating coating, so that the lubricity of the coating is maintained, and the firmness of the coating is improved.
The second objective of the present invention is to provide a medical catheter coated with the above coating, wherein the coating is formed by linking the bottom substance physically adsorbed or chemically bonded to the base material and the hyaluronic acid (sodium) on the top layer by covalent bond grafting with a cross-linking agent, so as to form a hydrophilic lubricating coating, and the coating has the advantages of good firmness, lubricity and biocompatibility.
The third objective of the present invention is to provide a medical device, wherein a crosslinking agent is used to covalently graft the bottom layer material physically adsorbed or chemically bonded to the substrate and the top layer hyaluronic acid (sodium) to form a hydrophilic lubricating coating, which has the advantages of good firmness, lubricity and biocompatibility.
The technical scheme of the invention is as follows:
the utility model provides a thermosetting sodium hyaluronate coating, includes top layer, bottom and cross-linking agent, the subject material of top layer is hyaluronic acid or sodium hyaluronate, the subject material of bottom is aqueous macromolecular material, the cross-linking agent is many functional group molecule, the cross-linking agent contains hydrophilic end and hydrophobic end, the cross-linking agent respectively through hydrophilic end, hydrophobic end with the top layer reaches the bottom crosslinking.
The biological toxicity generated by the migration and precipitation of the cured small molecular substances is reduced by selecting the aqueous high molecular emulsion in the bottom layer, and the pollution of an organic solvent to the environment and operators is reduced; the cross-linking agent molecules are covalently bonded with the top layer and the bottom layer simultaneously, so that the hydrophilic coating has good firmness, lubricity and biocompatibility.
In some embodiments, the cross-linking agent is terminated with the aqueous high molecular polymer and the siloxane, and has a molecular structure comprising a carbodiimide group, a hydrazide group, or an isocyanate covalently bonded to the top layer; or the cross-linking agent takes siloxane group, hydrazide group, isocyanate and carbodiimide group as end groups, and the molecular structure of the cross-linking agent contains the aqueous high molecular polymer.
In some embodiments, the crosslinker has the general formula (I):
wherein R is 5 Selected from: -R 21 C(O)NHR 22 -、-R 21 C(O)OR 22 -or-R 21 OC(O)R 22 -，R 4 Selected from: -SiOC 1-5 Alkyl, -C (O) NH-, -NCO or-NCN (carbodiimide group); l is an aqueous high molecular polymer, R 6 Is C 1-5 Alkyl, substituted or unsubstituted aryl; r 21 And R 22 Each independently selected from: c 1-10 Alkyl radical, C 1-10 Alkoxy, substituted or unsubstituted aryl, C 1-5 alkyl-NR d -C 1-5 Alkyl radical, R d Selected from hydrogen or C 1-5 An alkyl group.
The cross-linking agent is formed by coupling three parts, namely a water-based high-molecular polymer base, a hydrophobic end bonded with the bottom layer and a hydrophilic end bonded with the top layer, the hydrophobic end is compatible with the bottom layer by the water-based high-molecular polymer base, the cross-linking agent forms an amphiphilic structure, and hyaluronic acid (sodium) physically adsorbed or chemically bonded on the bottom layer and the top layer of the base material can be connected in a covalent bond grafting mode, so that the cross-linking of the top layer and the bottom layer is firmer, the toxicity is lower, and the biocompatibility is good.
In some embodiments, the aqueous high molecular polymer is selected from: at least one of PEG, PEO, TWEEN, PVA, or PVP. The aqueous high molecular polymer makes the hydrophobic end of the molecular structure of the cross-linking agent compatible with the bottom resin.
In some embodiments, the crosslinking agent is located in the bottom layer, the bottom layer comprises the aqueous polymeric material and the crosslinking agent, the top layer comprises hyaluronic acid or sodium hyaluronate, and the top layer is free of the crosslinking agent, which reduces the toxicity of the coating. In some embodiments, the cross-linking agent is located on the top layer, i.e., the top layer comprises hyaluronic acid or sodium hyaluronate and the cross-linking agent, and the bottom layer comprises an aqueous polymeric material. In some embodiments, the top layer and the bottom layer each comprise the cross-linking agent, i.e., the top layer comprises hyaluronic acid or sodium hyaluronate and the cross-linking agent, and the bottom layer comprises an aqueous polymeric material and the cross-linking agent. Wherein, the cross-linking agent molecule is covalently bonded with the bottom layer through the hydrophobic end and is covalently bonded with the top layer through the hydrophilic end, so that the top layer and the bottom layer are firmly cross-linked.
In some embodiments, the amount of the cross-linking material in the bottom layer is 30 to 100 parts by weight, and the amount of the cross-linking agent is 0.1 to 20.0 parts by weight.
In some embodiments, the weight part of hyaluronic acid or sodium hyaluronate in the top layer is 0.1-5.0, and the weight part of the crosslinking agent is 0.01-10.0.
In some embodiments, the molecular weight of the cross-linking agent is in the range of 200-.
In some embodiments, the underlayer host material is selected from: acrylate, water-based polyurethane, polyacrylate and their mixture in any proportion.
The invention also provides a medical catheter coated with the coating.
In the medical catheter, the coating is coated by brushing, dipping or spraying, and then is heated to be cured, wherein the heating temperature is 30-100 ℃, and the heating time is 0.5-3 h.
The invention also provides a device coated with a coating as described in any of the above, or comprising a catheter as described above.
The coating curing mechanism of the invention is as follows:
the siloxane structure of the hydrophobic end of the cross-linking agent and the hydroxyl of the bottom material are subjected to hydrolytic condensation reaction to form a covalent bond structure of-O-Si-O-; the hydrazide, siloxane, carbodiimide structure at the hydrophilic end of the crosslinker condenses with the hydroxyl or carboxyl groups in the sodium hyaluronate structure in the top layer, thereby grafting sodium hyaluronate to the surface of the bottom layer. The aqueous high molecular polymer in the cross-linking agent molecule plays a role in promoting the dissolution and uniform dispersion of the hydrophobic end, and the top layer are solidified as shown in figure 1.
Compared with the prior art, the invention has the following beneficial effects:
according to the heat-cured sodium hyaluronate coating, the medical catheter and the instrument, hyaluronic acid (sodium) at the bottom layer and the top layer are connected in a covalent bond grafting mode through the cross-linking agent to form the hydrophilic lubricating coating, so that the lubricity of the coating is maintained, the firmness of the coating is improved, and the coating has good biocompatibility, is non-toxic and harmless to a human body and has no cytotoxicity; when the cross-linking agent is positioned on the bottom layer, the top layer can also play a role in connecting the top layer and the bottom layer without grafting the cross-linking agent, so that the toxicity is reduced.
Of course, it is not necessary for any product in which the invention is practiced to achieve all of the above-described advantages at the same time.
Drawings
FIG. 1 is a schematic view of the cured structure of the bottom and top layers of the coating of the present invention;
FIG. 2 is an IR spectrum of a crosslinking agent A of example 1 of the present invention;
FIG. 3 is a schematic partial view of a nuclear magnetic spectrum of a crosslinking agent A of example 1 of the present invention;
FIG. 4 is a diagram illustrating the push test results of embodiment 2 of the present invention;
fig. 5 is a schematic diagram of push test results in embodiment 3 of the present invention.
Detailed Description
The invention provides a cross-linking agent for a hydrophilic coating, which is an amphiphilic structure and reacts with residual hydroxyl in a bottom-layer macromolecule through hydrolysis condensation reaction of silicon methoxyl to form cross-linking, and the structure of the cross-linking agent is shown as (I-I), (I-II) or (I-III):
wherein R is 1 、R 2 Is a coupling group of which-R 2 -R 1 -is selected from: -R 21 OR 22 -、-R 21 C(O)NR 22 -、-R 21 NC(O)R 22 、-R 21 C(O)OR 22 -or-R 21 OC(O)R 22 -, in which R 21 、R 22 Selected from: c 1-10 Alkyl radical, C 1-10 Alkoxy, aryl, C 1-5 alkyl-NR d -C 1-5 Alkyl radical, R d Selected from hydrogen or C 1-5 An alkyl group; r is 3 Selected from the group consisting of: c 1-5 Alkyl radical, C 1-5 Alkoxy or aryl.
In this context, it is to be noted that THF, i.e.tetrahydrofuran, and TEA, i.e.triethylamine, are used.
In this context, it is to be noted that "C" is 1-10 Alkyl "refers to straight and branched chain saturated aliphatic hydrocarbon groups containing 1 to 10 carbon atoms, similarly defined below; more preferably C 1-8 Alkyl groups, non-limiting examples include: methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, sec-butyl group, n-pentyl group, 1-dimethylpropyl group, 1, 2-dimethylpropyl group, 2-dimethylpropyl group, 1-ethylpropyl group, 2-methylbutyl group, 3-methylbutyl group, n-hexyl group, 1-ethyl-2-methylpropyl group, 1, 2-trimethylpropyl group, 1-dimethylbutyl group, 1, 2-dimethylbutyl group, 2-dimethylbutyl group, 1, 3-dimethylbutyl group, 2-ethylbutyl group, 2-methylpentyl group, 3-methylpentyl group, 4-methylpentyl group, 2, 3-dimethylbutyl group, n-heptyl group, 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 2-methylpentyl group, 3-methylhexyl group, 4-methylhexyl group, 2-dimethylpropyl group, 2-pentyl group, 2-methylpropyl group, 2-methyl-pentyl group, 3-pentyl group, 2-methyl-pentyl group, 2-pentyl group, and 3-pentyl group, 5-methylhexyl, 2, 3-dimethylpentyl, 2, 4-dimethylpentyl, 2-dimethylpentyl, 3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2, 3-dimethylhexyl, 2, 4-dimethylhexyl, 2, 5-dimethylhexyl, 2-dimethylhexyl, 3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2-diethylpentyl, n-decyl, 3-diethylhexyl, 2-diethylhexyl, various branched isomers thereof, and the like.
As used herein, "C" is 1-10 Alkoxy means-O- (C) 1-10 Alkyl) wherein alkyl is as defined above. Preferably C 1-8 An alkoxy group.
Aryl is phenyl or pyridyl.
The aryl, alkyl and alkoxy can be substituted by any 1, 2 or 3 substituents selected from the following group: halogen (F, Cl, Br or I), hydroxy, carboxy, amino, C 1-5 Alkyl radical, C 1-5 Alkoxy, mercapto, aryl, C 3-8 Cycloalkyl, C 3-8 A heterocycloalkyl group.
In this context, it should be noted that the coating is also referred to as a hydrophilic lubricating coating and also referred to as a hydrophilic coating, i.e., the heat-curable sodium hyaluronate coating according to the present invention.
In this context, it is to be noted that a plurality of R's are present in one formula 3 Substituent, a plurality of R 3 The substituents may be the same or different from each other.
In this context, a range of values from one value to another is a general expression avoiding any recitation of all values in the range in the specification. Thus, recitation of a specific range of values herein includes any number within the range and any smaller range of values within the range, as if the range and smaller range were explicitly recited in the specification.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are only for illustrating the present invention and are not intended to limit the scope of the present invention. In practice, the invention will be understood to cover all modifications and variations of the invention as may be practiced by those skilled in the art.
Example 1
1.1 Synthesis of crosslinker A:
weighing 1g of amino silane (KBM-603,226g/mol, a national reagent) and 10g of HO-PEG-COOH (a national reagent, PEG molecular weight is 2000g/mol) in 50ml of dichloromethane, dropwise adding 5ml of thionyl chloride for 0.5h under ice bath, heating to 30 ℃ for reaction for 2h, rotationally evaporating to remove the solvent and thionyl chloride, reacting with 0.48g of chloroacetic acid in THF, using TEA as an alkali, heating for reflux reaction for 8h, rotationally evaporating THF, adding 100ml of ethyl acetate and saturated NaCl water (volume ratio 1:1) for extraction, taking an organic layer to rotationally evaporate ethyl acetate, mixing with 0.2g of hydrazine hydrate (a national reagent) by using 30ml of dichloromethane as a solvent, slowly dropwise adding 5ml of thionyl chloride under ice bath, heating to 30 ℃ after dropwise adding, reacting for 1h to generate a cross-linking agent A, rotationally evaporating the solvent, adding saturated ice water, and depositing NaCl in a lower layer, the lower oily substance was extracted as a crosslinking agent A (6g) by separating with a separating funnel and was used. Wherein, the structure of the cross-linking agent A is as follows: NH (NH) 2 NHCOCH 2 O(C 2 H 4 O) n CON(CH 2 ) 2 NH(CH 2 ) 3 Si(OCH 3 ) 3 The molecular weight is 2356 g/mol.
Cross-linker A was analyzed by PE specrum 100 FTIR as shown in FIG. 2, 3436.92cm -1 Is the NH peak of the hydrazide, 1724.46cm -1 Is the carbonyl peak of the acyl group, 1114.76cm -1 Is the carbon oxygen peak in PEG. And (3) detecting by Brucker AV-300 type HNMR, analyzing the crosslinking agent A, dissolving the crosslinking agent A5mg in deuterated chloroform for testing, mainly analyzing the nuclear magnetism peak of silicon methoxyl, wherein the spectrum is shown in figure 3, and the peak delta-3.5 ppm is the peak of hydrogen in methoxyl connected with Si.
Different PEG structures, different siloxane structures, and different carboxylic acids are selected, and different cross-linkers II-I can be synthesized: NH (NH) 2 NHC(O)R a O(C 2 H 4 O) n C(O)NR b Si(OR c ) 3 Wherein R is a 、R b Is an alkyl carbon chain, R a Carbon chain of 1-5 carbons, R b Carbon chain of 5-10 carbons, R c Is C 1-5 Preferably C 1-3 . Furthermore, the aqueous high molecular polymer can also be selected from PEO and TWEENPVA or PVP can also be coupled to siloxane, carboxylic acid, hydrazine to form a cross-linking agent comprising a waterborne polymer, siloxane and amide groups within the molecule to cross-link the top and bottom layers.
Wherein, it is to be noted that the crosslinking agent A is only a non-limiting example, and R is a 、R b Does not affect the crosslinking function of the crosslinking agent and can be prepared by selecting proper raw materials according to actual requirements.
1.2 Synthesis of crosslinker B:
weighing 1g of aminosilane (KH-540,179.3g/mol, Chinese medicine reagent) and 10g of HO-PEG-COOH (Chinese medicine reagent, PEG molecular weight is 2000g/mol) in 50ml of dichloromethane, dropwise adding 5ml of thionyl chloride for 0.5h under ice bath, heating to 30 ℃ for reaction for 2h, drying the solvent and thionyl chloride by rotary evaporation, adding 1g of Hexamethylene Diisocyanate (HDI) (168.2g/mol, Chinese medicine reagent) and 3-methyl-1-phenyl-2-phosphole-1-oxide (MPPO) as catalysts, and adding N-methyl-1-phenyl-2-phosphole-1-oxide (MPPO) as a catalyst 2 Protection, mechanical stirring, anhydrous and anaerobic reaction at 120 ℃ for 2h, and infrared monitoring of the reduction of the absorption peak of the isocyanate group, which indicates the completion of the reaction. Then petroleum ether is extracted, and 10.6g of cross-linking agent B is obtained by taking the lower layer, wherein the structure of the cross-linking agent B is shown as follows:
example 2
This example 2 provides a hydrophilic lubricating coating for a minimally invasive cardiovascular stent pusher, where the stent pusher is formed by extruding pebax and nylon materials and then welding the extruded materials. In order to reduce the resistance of the stent during the delivery, the surface of the delivery catheter needs to be lubricated, and a hydrophilic coating is usually formed on the surface of a delivery device. The hydrophilic lubricating coating on the market at present is a PVP coating, although in a non-curve area, the friction force is small, and the pushing force is small. However, since PVP has low water absorption, it deforms and squeezes when the conveyer passes through a curve, water on the surface of PVP is easily squeezed off, and the friction force increases, so that the pushing force increases when the conveyer passes through a curve, which affects the operability of a doctor and brings a risk to an operation.
In the sodium hyaluronate coating formula of the embodiment, the synthetic cross-linking agent A is added into the bottom layer, and the cross-linking agent is not needed to be added into the top layer, so that the use of the cross-linking agent can be reduced, the cross-linking agent in the top layer can be prevented from generating toxicity to a human body after the top layer is detached, and the coating cytotoxicity of the coating can be reduced. Of course, in some alternative embodiments, a cross-linking agent may also be added to the top layer.
The preparation method of the hydrophilic lubricating coating of the embodiment includes the specific preparation conditions shown in table one, including the specific material types and weight parts of each component in the top layer and the bottom layer, and the curing temperature and time, and includes the following specific operation steps:
(1) respectively taking the components in parts by weight of the top layer and the bottom layer in the table I into different containers, respectively stirring for 1-2 hours by magnetic force until the solutions are uniformly mixed, and then respectively filtering to obtain a top layer solution and a bottom layer solution;
(2) taking the Pebax substrate, firstly cleaning the Pebax substrate by ethanol, removing grease on the surface of the substrate to obtain a clean Pebax substrate, then coating the bottom layer solution, coating the top layer solution after curing, finally curing to obtain the substrate coated with the hydrophilic lubricating coating, sealing and packaging to prevent moisture absorption.
2.1 Pushing Performance testing
Soaking the base material coated with the hydrophilic lubricating coating in pure water or normal saline for 1min, taking out, and testing the pushing force by using pushing equipment; while the PVP coated substrate was used as a control.
Pushing test conditions: pushing distance: 140mm, push speed: 10mm/s, mold material push: PTFE. The smaller the pushing force is, the easier the doctor operates, and the stent delivery is facilitated.
The results are shown in fig. 4, where the catheter of this example, after application of the coating, showed a significant reduction in the push force in the second and third bends, and the coating reduced the push force better than the PVP coating.
2.2 chemical Property testing
The chemistry was tested according to the GB/T14233.1-2008 standard, the standard requirement was that it could not be greater than 2ml, and the test value for the coating prepared in this example 2 was 1.2ml, as shown in Table two. Therefore, the chemical properties of the coating prepared in the embodiment 2 meet the requirements of GB/T14233.1-2008.
Watch two
2.3 cytotoxicity assays
Cytotoxicity was tested according to ISO10993-5:2009 standard with standard requirements of greater than 70%, and the test results for the coating prepared in this example 1 were 85.7%, as shown in table three. Thus, the cytotoxicity of the coating prepared in this example 2 meets the requirements of ISO10993-5: 2009.
Watch III
| Blank space | Hyaluronic |
|
| 100 |
100% | |
| Parallel sample | ||
| 1 | 0.782 | 0.71 |
| Parallel sample 2 | 0.786 | 0.706 |
| Parallel sample 3 | 0.817 | 0.667 |
| Parallel sample 4 | 0.806 | 0.682 |
| |
0.769 | 0.704 |
| Mean value | 0.792 | 0.6938 |
| Toxicity ratio | 87.50％ |
Example 3
The stent pusher catheter was prepared with a hydrophilic coating using a method similar to that of example 2, and the pusher force was tested using crosslinker B as the bottom crosslinker.
The result is shown in FIG. 5, where the pushing force is the second and third bends at 70g and 90g, respectively. If the catheter is uncoated, the catheter cannot pass through a curve because the frictional force is too great, indicating better lubricity.
Comparative example 1
A certain commercially available water-based cross-linking agent Bayhydur 305 is adopted as a cross-linking agent, the formula is shown in Table four, pebax is used as a base material, and the cytotoxicity is tested by using ISO10993-5:2009 after coating, and the test result is 38.78% (Table five).
Watch four
Watch five
| Blank space | Bayhydur 305 |
|
| 100 |
100% | |
| Parallel sample | ||
| 1 | 0.864 | 0.328 |
| Parallel sample 2 | 0.857 | 0.311 |
| Parallel sample 3 | 0.864 | 0.321 |
| Parallel sample 4 | 0.858 | 0.36 |
| |
0.874 | 0.354 |
| Mean value | 0.8634 | 0.3348 |
| Toxicity ratio | 38.78％ |
While the foregoing is directed to the preferred embodiment of the present invention, it is not intended to detail all of the same, and it is to be understood that such embodiment is merely illustrative of the present invention and is not to be considered as limiting the scope of the invention, which is limited only by the claims and their full scope and equivalents.
The embodiments were chosen and described in order to best explain the principles of the invention and the practical application, to thereby enable others skilled in the art to best utilize the invention. In light of the above teachings, those skilled in the art will readily appreciate that the materials and their equivalents, the processes and their equivalents, as listed or exemplified herein, are capable of performing the invention in any of its several forms, and that the upper and lower limits of the parameters of the materials and processes, and the ranges of values between these limits are not specifically enumerated herein.
Claims (13)
1. The utility model provides a thermosetting sodium hyaluronate coating, includes top layer, bottom and cross-linking agent, the host material of top layer is hyaluronic acid or sodium hyaluronate, the host material of bottom is water-based macromolecular material, its characterized in that, the cross-linking agent is the polyfunctional group molecule, the cross-linking agent contains hydrophilic end and hydrophobic end, the cross-linking agent respectively through hydrophilic end, hydrophobic end with the top layer reaches the bottom crosslinking.
2. The heat-cured sodium hyaluronate coating according to claim 1, wherein the cross-linking agent is terminated by a water-based high molecular polymer and siloxane, and the molecular structure of the cross-linking agent comprises carbodiimide groups, hydrazide groups or isocyanate;
or the cross-linking agent takes siloxane group, hydrazide group, isocyanate and carbodiimide group as end groups, and the molecular structure of the cross-linking agent comprises aqueous high molecular polymer.
3. The thermally cured sodium hyaluronate coating of claim 2, wherein the cross-linking agent has the general formula of formula (I):
wherein R is 5 Selected from: -R 21 C(O)NHR 22 -、-R 21 C(O)OR 22 -or-R 21 OC(O)R 22 -，R 4 Selected from: -SiOC 1-5 Alkyl, -C (O) NHNH 2 -NCO or-NCN; l is an aqueous high molecular polymer, R 6 Is C 1-5 Alkyl, aryl; r 21 And R 22 Each independently selected from: c 1-10 Alkyl radical, C 1-10 Alkoxy, aryl, C 1-5 alkyl-NR d -C 1-5 Alkyl radical, R d Selected from hydrogen or C 1-5 An alkyl group.
4. The thermally cured sodium hyaluronate coating according to claim 2 or 3, wherein said aqueous high molecular weight polymer is selected from the group consisting of: at least one of PEG, PEO, TWEEN, PVA, or PVP.
5. The thermally cured sodium hyaluronate coating according to claim 1, wherein the cross-linking agent is located in the top layer or the cross-linking agent is located in the bottom layer.
6. The thermally cured sodium hyaluronate coating of claim 1, wherein the top layer and the bottom layer each comprise the cross-linking agent.
7. The heat-cured sodium hyaluronate coating according to claim 5 or 6, wherein the crosslinking reaction substance in the bottom layer is 30-100 parts by weight, and the crosslinking agent is 0.1-20.0 parts by weight.
8. The heat-cured sodium hyaluronate coating according to claim 5 or 6, wherein the weight part of hyaluronic acid or sodium hyaluronate in the top layer is 0.1-5.0, and the weight part of the crosslinking agent is 0.01-10.0.
9. The coating of sodium hyaluronate according to claim 1, wherein the cross-linking agent has a molecular weight in the range of 200-.
10. The thermally cured sodium hyaluronate coating of claim 1, wherein the primer host material is selected from the group consisting of: acrylate, water-based polyurethane, polyacrylate and their mixture in any proportion.
11. Medical catheter, characterized in that it is coated with a coating according to any one of claims 1 to 10.
12. The medical catheter of claim 11, wherein the coating is applied by brushing, dipping or spraying and then cured by heating at a temperature of 30-100 ℃ for 0.5-3 h.
13. A device coated with a coating as claimed in any one of claims 1 to 10 or comprising a medical catheter as claimed in claim 11 or 12.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060115513A1 (en) * | 2004-11-29 | 2006-06-01 | Hossainy Syed F A | Derivatized poly(ester amide) as a biobeneficial coating |
| JP2007128864A (en) * | 2005-10-07 | 2007-05-24 | Ishihara Sangyo Kaisha Ltd | Fluid composition, and electrode, wiring pattern, as well as coating film formed by using it, and decoration goods forming the coating film |
| CN103119084A (en) * | 2010-07-28 | 2013-05-22 | 斯塔尔国际有限公司 | Process for the preparation of multifunctional polycarbodiimides which are used as crosslinking agents |
| CN106334219A (en) * | 2016-08-25 | 2017-01-18 | 百诺奥医学科技（苏州）有限公司 | Hyaluronic acid modified hydrophilic lubricating coating, preparation method and applications thereof |
| CN109563199A (en) * | 2016-06-13 | 2019-04-02 | 麻省理工学院 | For reducing the biocompatibility amphoteric ion polymer coating and hydrogel of foreign body reaction and fibrosis |
| US20200239601A1 (en) * | 2019-01-30 | 2020-07-30 | Bausch & Lomb Incorporated | Crosslinked polymeric network and use thereof |
-
2021
- 2021-03-09 CN CN202110255509.0A patent/CN115040699A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060115513A1 (en) * | 2004-11-29 | 2006-06-01 | Hossainy Syed F A | Derivatized poly(ester amide) as a biobeneficial coating |
| JP2007128864A (en) * | 2005-10-07 | 2007-05-24 | Ishihara Sangyo Kaisha Ltd | Fluid composition, and electrode, wiring pattern, as well as coating film formed by using it, and decoration goods forming the coating film |
| CN103119084A (en) * | 2010-07-28 | 2013-05-22 | 斯塔尔国际有限公司 | Process for the preparation of multifunctional polycarbodiimides which are used as crosslinking agents |
| CN109563199A (en) * | 2016-06-13 | 2019-04-02 | 麻省理工学院 | For reducing the biocompatibility amphoteric ion polymer coating and hydrogel of foreign body reaction and fibrosis |
| CN106334219A (en) * | 2016-08-25 | 2017-01-18 | 百诺奥医学科技（苏州）有限公司 | Hyaluronic acid modified hydrophilic lubricating coating, preparation method and applications thereof |
| US20200239601A1 (en) * | 2019-01-30 | 2020-07-30 | Bausch & Lomb Incorporated | Crosslinked polymeric network and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 兰永强等: "《分离生物乙醇用渗透汽化复合膜》", vol. 1, 厦门大学出版社, pages: 58 - 61 * |
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