CN107987105B - A kind of H can be used for dressing for skin2S donor compound, sponge dressing and preparation method - Google Patents
A kind of H can be used for dressing for skin2S donor compound, sponge dressing and preparation method Download PDFInfo
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- CN107987105B CN107987105B CN201711192470.2A CN201711192470A CN107987105B CN 107987105 B CN107987105 B CN 107987105B CN 201711192470 A CN201711192470 A CN 201711192470A CN 107987105 B CN107987105 B CN 107987105B
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- dressing
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000000648 calcium alginate Substances 0.000 claims abstract description 17
- 235000010410 calcium alginate Nutrition 0.000 claims abstract description 17
- 229960002681 calcium alginate Drugs 0.000 claims abstract description 17
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=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](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 claims abstract description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 74
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 54
- 239000000243 solution Substances 0.000 claims description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 28
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 18
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 18
- 239000000661 sodium alginate Substances 0.000 claims description 18
- 235000010413 sodium alginate Nutrition 0.000 claims description 18
- 229940005550 sodium alginate Drugs 0.000 claims description 18
- 239000007789 gas Substances 0.000 claims description 14
- 238000004132 cross linking Methods 0.000 claims description 11
- 239000013067 intermediate product Substances 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 9
- 238000004108 freeze drying Methods 0.000 claims description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 8
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 239000012043 crude product Substances 0.000 claims description 7
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 claims description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 6
- 235000010443 alginic acid Nutrition 0.000 claims description 5
- 229920000615 alginic acid Polymers 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 239000004809 Teflon Substances 0.000 claims description 4
- 229920006362 Teflon® Polymers 0.000 claims description 4
- 229910052786 argon Inorganic materials 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 4
- 238000005374 membrane filtration Methods 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 150000004702 methyl esters Chemical class 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 229960001126 alginic acid Drugs 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 claims description 2
- 150000004781 alginic acids Chemical class 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims 2
- FMHXHMLHGIPODY-UHFFFAOYSA-N 2,2-dichloropropanenitrile Chemical compound CC(Cl)(Cl)C#N FMHXHMLHGIPODY-UHFFFAOYSA-N 0.000 claims 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 239000011575 calcium Substances 0.000 claims 1
- 229910052791 calcium Inorganic materials 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 abstract description 22
- 239000006227 byproduct Substances 0.000 abstract description 12
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 11
- 206010072170 Skin wound Diseases 0.000 abstract description 2
- 230000002500 effect on skin Effects 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract description 2
- 238000011287 therapeutic dose Methods 0.000 abstract description 2
- 206010052428 Wound Diseases 0.000 description 20
- 210000003491 skin Anatomy 0.000 description 10
- 230000029663 wound healing Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 6
- 230000035876 healing Effects 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000007599 discharging Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229940072056 alginate Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000009036 growth inhibition Effects 0.000 description 3
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 3
- KPNBUPJZFJCCIQ-LURJTMIESA-N methyl L-lysinate Chemical class COC(=O)[C@@H](N)CCCCN KPNBUPJZFJCCIQ-LURJTMIESA-N 0.000 description 3
- 230000035790 physiological processes and functions Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000004043 responsiveness Effects 0.000 description 3
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical group NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YZMHNNLDUWRZFW-UHFFFAOYSA-N (4-methoxyphenyl)-morpholin-4-yl-sulfanyl-sulfanylidene-$l^{5}-phosphane;morpholine Chemical compound C1COCC[NH2+]1.C1=CC(OC)=CC=C1P([S-])(=S)N1CCOCC1 YZMHNNLDUWRZFW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- YDYLLKOOCYPMPN-UHFFFAOYSA-N N#CC(CCl)(O)Cl Chemical compound N#CC(CCl)(O)Cl YDYLLKOOCYPMPN-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 210000001126 granulation tissue Anatomy 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 230000005588 protonation Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000002341 toxic gas Substances 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 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 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229960001413 acetanilide Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 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
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 230000031990 negative regulation of inflammatory response Effects 0.000 description 1
- 230000031972 neutrophil apoptotic process Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 150000004763 sulfides Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/44—Amides thereof
- C07F9/4461—Amides thereof the amide moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4465—Amides thereof the amide moiety containing a substituent or a structure which is considered as characteristic of aliphatic amines
-
- 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
- A61L24/0015—Medicaments; Biocides
-
- 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
- A61L24/0036—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Surgery (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Materials For Medical Uses (AREA)
Abstract
A kind of H can be used for dressing for skin2S donor compound, sponge dressing and preparation method, are related to H2S donor compound, sponge dressing and preparation method.The first purpose of the invention is to provide a kind of H that can be used for dressing for skin2S donor compound CW-1, the compound can be specifically to dermal delivery H2S gas molecule, by-product have antibacterial action simultaneously.A second object of the present invention is to provide the dressing suitable for skin, it be include H2The sponge dressing of the calcium alginate of S donor compound CW-1.The dressing can be contacted with skin wound, can effectively deliver the H with therapeutic dose long-term and stably to wound location skin2S gas molecule, while playing antibacterial action.
Description
Technical field
The present invention relates to a kind of H2S donor compound, sponge dressing and preparation method.
Background technique
H2S is a kind of colourless gas molecule with rotten egg smell, for a long time by it is believed that being that one kind will cause
The toxic gas of environmental pollution.However, recent study finds toxic gas molecule H2The same nitric oxide of S (NO) and carbon monoxide
(CO) equally, it is a kind of important endogenous gas signaling molecule, participates in a variety of pathological processes.In the mammalian body
H can be synthesized2S is mainly catalyzed cysteine generation by cystathionie-γ-lyases (CSE) and cystathionie-beta-synthetase (CBS)
Xie Erlai.The H in cardiovascular system2S is mainly catalyzed and synthesized by CSE, and H in nervous system2S is mainly catalyzed and synthesized by CBS.It is raw
H under the conditions of reason2The concentration of S is 1-160 μM, and 50-160 μM is reached in midbrain, reaches 10-160 μM in blood.Endogenous H2S has
Multiple biological function, can regulate and control maincenter and peripheral neverous system, regulating cell metabolism, to adjust immune/inflammation anti-
The function of answering, adjust cardiovascular system, inflammation, septicemia, shock, in terms of effect caused the wide of people
General concern.
H2The physiological function of S mainly reduces inflammation by following several approach, and protective tissue organ escapes injury.H2S
Inhibit leukocyte in the blood vessels skin, inhibit leucocyte overflow and oedema formation.H2S can replace oxygen nebulization line grain
Body breathing, to weaken tissue damage caused by oxidation is pressed.H2S is able to suppress the activity of phosphodiesterase (PDEs) to diastole
Vascular smooth muscle increases blood flow.H2S drives M2 type of the macrophage to anti-inflammatory by starting neutrophil apoptosis
Differentiation is to reduce inflammatory reaction.H2S can inhibit the activity of transcription factor NF-kB, thus during reducing proinflammatory
The generation of cell factor.H2S increases in the yield of wound site, and then passes through the healing of stimulation vascularization acceleration of wound.
Existing result of study shows H2S's promotes the function of angiogenesis and anti-inflammatory response to have wound healing
There is apparent facilitation.Therefore, endogenous H is improved2The synthesis of S or the exogenous H for delivering debita spissitudo2S, which becomes, clinically to be added
Effective treatment means of fast wound healing.Moreover, H2S can not need the carrier of any specificity just as gaseous signal molecule
Intracellular biological targets can be reached quickly through cell membrane, to play a series of biological effect.But H2S with NO and
CO is the same, and physiological function has dose dependent, and when low concentration can play physiological function and cytoprotection, and highly concentrated
Then there is certain cytotoxicity when spending.Therefore, H that is lasting by carrier appropriate, controllably discharging debita spissitudo2S, can be with
Make H2S becomes a kind of effective therapeutic reagent.In general, H2S carrier is in release H2After S gas molecule, it will generate useless
By-product.But if a kind of bioactive molecule is connected to H simultaneously2On S carrier, H is discharged2By-product generated after S gas molecule
Object will be provided with the function of bioactive molecule, achieve the effect that turn waste into wealth.
NaS and NaHS is the H being commonly used at present2S donor compound, these sulphide salts can be spontaneous in aqueous solution
The H of ground quick release high concentration2S, but this delivery mode is difficult to control H2The concentration of S in aqueous solution, and H2S is in water
Concentration in solution can due to gas volatilization and quickly reduce.These properties significantly limit H2The use of S clinically.
Therefore, novel H is developed2S donor compound is to overcome the shortcomings of that existing donor compound has received vast concern.To current
Until, it has been reported that several novel H2S donor compound, H2The release of S can be hydrolyzed, photodissociation, the active control of cellular thiols
System.Wherein GYY4137 is a kind of most common donor compound, can hydrolyze in water and slowly discharge H2S, but it is this
Delivery mode is excessively slow, needs the help ability fast hydrolyzing of the organic solvents such as acetone or chloroform, and complete hydrolysis then needs
71 days.The nuclear structure or thiophosphate of GYY4137 is considered as design H2Effective template of S donor compound, still
There is still a need for develop new activation mechanism.Meanwhile studying H2The releasing mechanism of S and the property of by-product can preferably utilize H2S
Donor compound.
Summary of the invention
The first purpose of the invention is to provide a kind of H that can be used for dressing for skin2S donor compound CW-1, the chemical combination
Object can be specifically to dermal delivery H2S gas molecule, by-product have antibacterial action simultaneously.Second mesh of the invention
Be to provide a kind of dressing suitable for skin, it be include H2The sponge dressing of the calcium alginate of S donor compound CW-1.It should
Dressing can be contacted with skin wound, can effectively be delivered long-term and stably to wound location skin with therapeutic dose
H2S gas molecule, while playing antibacterial action.
A kind of H can be used for dressing for skin of the invention2S donor compound, its chemical structural formula are as follows:
A kind of H can be used for dressing for skin of the invention2The preparation method of S donor compound, it is according to the following steps
It carries out:
One, under the conditions of argon gas protection, 0 DEG C, 3- is added into the anhydrous methylene chloride solution of phenyl phosphinylidyne dichloro
Hydroxypropionitrile and triethylamine obtain reaction solution after mixing；Wherein, 3- hydroxypropionitrile, triethylamine, phenyl phosphinylidyne dichloro with
The molar ratio of methylene chloride is 1:1:1:18~19；
Two, reaction solution continues after 0 DEG C of reaction 15min in room temperature reaction 3h；
Three, 6- (to acetamido benzsulfamide)-L-lysine is added in the reaction system obtained after reacting to step 2
The mixed solution of methyl esters, triethylamine and anhydrous methylene chloride, the reaction was continued 3h；Wherein, 6- (to acetamido benzsulfamide)-
The molar ratio of L-lysine methyl esters, triethylamine and anhydrous methylene chloride is 1.1:3:18~19；
Four, methylene chloride is added in the solution after step 3 reaction, and successively uses 2M H2SO4Washing, MgSO4It is dry,
It is finally concentrated under reduced pressure, obtains crude product；Wherein, the volume ratio of the solution after methylene chloride is reacted with step 3 is 1:1；
Five, crude product is obtained into yellow oily intermediate product by chromatography, into the methanol solution of intermediate product
The LiOH solution newly prepared is added, is concentrated after stirring 12h at room temperature；The volume ratio of the methanol solution of LiOH solution and intermediate product
For 1:1；
Six, the solid after step 5 being concentrated, is resuspended in anhydrous methanol, through 0.2 μm of Teflon membrane filtration, then
It is concentrated freeze-dried, obtain H2S donor compound CW-1, the as H that can be used for dressing for skin2S donor compound.
A kind of sponge dressing of the invention, it be include H2The sponge dressing of the calcium alginate of S donor compound CW-1.
A kind of preparation method of sponge dressing of the invention, it is followed the steps below:
Firstly, the sodium alginate aqueous solution that mass percentage is 1~2% is added in mold, made by freeze-drying
For at sodium alginate sponge；
Then, sodium alginate sponge is crosslinked using the calcium chloride solution that concentration is 0.2~1.0M, by washing,
Freeze-drying obtains the calcium alginate sponge of crosslinking again；
Finally, H prepared by the claim 2 that concentration is 50mM is added dropwise into the calcium alginate sponge of crosslinking2S donor chemical combination
Object CW-1 solution, is freeze-dried again, obtains CA/CW-1 sponge dressing.
The H prepared by the present invention that can be used for dressing for skin2S donor compound CW-1 (lower abbreviation CW-1), can neutral and
H is discharged under the conditions of faintly acid pH2S, while its by-product has antibacterial ability.The property can make it be used for dressing for skin, hurt
H is specifically discharged under the subacidity pH environment of oral area position2S gaseous signal molecule promotes epithelialization and vascularization, improves simultaneously
Wound infection situation, the process of accelerating wound healing.CA/CW-1 sponge dressing prepared by the present invention has high-hygroscopicity, height thoroughly
Gas can largely absorb wound exudate, provide Moist healing environment for wound, and as the absorption of sepage is discharged to wound
H2S.H of the present invention2S donor compound and the dressing for skin of the molecule is loaded to chronic Hard agglut wound and infected wound
With unique therapeutic effect, rehabilitation can be brought to wish for patient, while prepare industry for dressing and bringing huge commercial opportunities, had very
Good Social benefit and economic benefit.
CW-1 of the invention occurs protonation under the conditions of neutral or subacidity pH and forms mercaptan, and then is attacked by nucleophilic carboxyl
Raw intramolecular cyclization is fired to form five-membered ring by-product while discharging H2S.H is discharged by CW-1 under detection condition of different pH2S's
Situation discovery, the structure can under the conditions of faintly acid pH (pH 5 and pH 6) a large amount of H of quick release2S, H within 5 minutes2S's releases
High-volume up to 90%, with the extension of time, the H of high concentration2S gas can be escaped from liquid, after 90 min H2S concentration is only remaining
50%.Under the conditions of neutral pH (pH 7.4), CW-1 slowly can constantly discharge H2S, after 90 min H2The burst size of S reaches
50%.And under the conditions of alkalescent pH (pH 8), CW-1 only discharges the H of trace2S.This H regulated and controled by pH of CW-12The release side S
Formula makes it in physiological conditions being capable of controlled release H2S bioactive molecule, therefore there are specific biological applications.
The present invention is crosslinked by bivalent cation (such as calcium ion) makes sodium alginate aqueous solution become alginate.It should
Gel has unique pH sensibility and coagulating effectiveness, and the differentiation and growth of energy sertoli cell.It is added in alginate dressing
H2S donor compound CW-1, it is high in conjunction with alginate dressing porosity, hygroscopicity is strong, at many advantages such as colloidality is good, it can effectively inhale
It receives a large amount of diffusates and forms hydrogel, provide good Moist healing environment for wound healing.It is sustainable with the absorption of sepage
Discharge H2S gaseous signal molecule, thus promote the proliferation of cell, creep and angiogenesis, accelerating wound healing process, release
H2Generated by-product has antibacterial action after S, will have unique curative effect for infected wound.
The present invention includes H2The sponge dressing of the calcium alginate of S donor compound CW-1 (apply by lower abbreviation CA/CW-1 sponge
Material) in H2The release of S has good pH responsiveness, under the conditions of 5.0,6.0,7.4,8.0 pH, with the reduction of pH value, applies
H is discharged in material2The ability of S gradually increases.Compared with free CW-1 molecule, the CW-1 that loads in CA/CW-1 sponge dressing can be with
Extend H2The release time of S simultaneously increases H2The burst size of S plays long-time controllable delivery H2The purpose of S.Due to wound location
PH value is acidity, therefore the CA/CW-1 dressing with pH responsiveness can be as the absorption of sepage be gradually to wound location specificity
Ground discharges H2S, while good Moist healing environment and antibacterial action are provided for wound.
Detailed description of the invention
Fig. 1 is H2The synthetic route schematic diagram of S donor compound CW-1；
Fig. 2 is that CW-1 discharges H2The schematic diagram of S；
Fig. 3 is H of the CW-1 under condition of different pH2S burst size result figure；Wherein, A is the burst size under pH 6.0, and B is
Burst size under pH 5.0, C are the burst size under pH 7.4, and D is the burst size under pH 8.0；
Fig. 4 is growth inhibition effect result figure of the CW-1 to E.coli；Wherein, wherein A is to test at pH 7.1, B
To be tested at pH 6.0；
Fig. 5 is growth inhibition effect result figure of the CW-1 to S.aureus；Wherein, A be at pH 7.1 test, B for
PH 6.0 is lower to be tested；
Fig. 6 is cytotoxicity test figure of the CW-1 to L929；Wherein, A is to test at pH 7.4, and B is at pH 6.0
Test；
Fig. 7 is the mouse wound healing process for applying CA/CW-1 sponge dressing.
Specific embodiment
Specific embodiment 1: a kind of H that can be used for dressing for skin of present embodiment2S donor compound, its chemistry
Structural formula are as follows:
Specific embodiment 2: a kind of H that can be used for dressing for skin of present embodiment2The preparation method of S donor compound,
It is followed the steps below:
One, under the conditions of argon gas protection, 0 DEG C, 3- is added into the anhydrous methylene chloride solution of phenyl phosphinylidyne dichloro
Hydroxypropionitrile and triethylamine obtain reaction solution after mixing；Wherein, 3- hydroxypropionitrile, triethylamine, phenyl phosphinylidyne dichloro with
The molar ratio of methylene chloride is 1:1:1:18~19；
Two, reaction solution continues after 0 DEG C of reaction 15min in room temperature reaction 3h；
Three, 6- (to acetamido benzsulfamide)-L-lysine is added in the reaction system obtained after reacting to step 2
The mixed solution of methyl esters, triethylamine and anhydrous methylene chloride, the reaction was continued 3h；Wherein, 6- (to acetamido benzsulfamide)-
The molar ratio of L-lysine methyl esters, triethylamine and anhydrous methylene chloride is 1.1:3:18~19；
Four, methylene chloride is added in the solution after step 3 reaction, and successively uses 2M H2SO4Washing, MgSO4It is dry,
It is finally concentrated under reduced pressure, obtains crude product；Wherein, the volume ratio of the solution after methylene chloride is reacted with step 3 is 1:1；
Five, crude product is obtained into yellow oily intermediate product by chromatography, into the methanol solution of intermediate product
The LiOH solution newly prepared is added, is concentrated after stirring 12h at room temperature；The volume ratio of the methanol solution of LiOH solution and intermediate product
For 1:1；
Six, the solid after step 5 being concentrated, is resuspended in anhydrous methanol, through 0.2 μm of Teflon membrane filtration, then
It is concentrated freeze-dried, obtain H2S donor compound CW-1, the as H that can be used for dressing for skin2S donor compound.
Specific embodiment 3: present embodiment is unlike specific embodiment two: phenyl phosphinylidyne dichloro
The concentration of anhydrous methylene chloride solution is 0.76M.It is other to be identical with embodiment two.
Specific embodiment 4: present embodiment is unlike specific embodiment two: the concentration of LiOH solution is 1M.
It is other to be identical with embodiment two.
Specific embodiment 5: present embodiment is unlike specific embodiment two: 3- hydroxypropionitrile, triethylamine,
The molar ratio of phenyl phosphinylidyne dichloro and methylene chloride is 1:1:1:18.2.It is other to be identical with embodiment two.
Specific embodiment 6: present embodiment is from 6- unlike specific embodiment two (to acetamido benzene sulfonyl
Amine)-L-lysine methyl esters, triethylamine and anhydrous methylene chloride molar ratio be 1.1:3:18.2.Other and specific embodiment
Two is identical.
Specific embodiment 7: a kind of sponge dressing of present embodiment, it be include H2The sea of S donor compound CW-1
The sponge dressing of calcium alginate.
Specific embodiment 8: a kind of preparation method of sponge dressing of present embodiment, it is characterised in that it be according to
What following steps carried out:
Firstly, the sodium alginate aqueous solution that mass percentage is 1~2% is added in mold, made by freeze-drying
For at sodium alginate sponge；
Then, sodium alginate sponge is crosslinked using the calcium chloride solution that concentration is 0.2~1.0M, by washing,
Freeze-drying obtains the calcium alginate sponge of crosslinking again；
Finally, H prepared by the claim 2 that concentration is 50mM is added dropwise into the calcium alginate sponge of crosslinking2S donor chemical combination
Object CW-1 solution, is freeze-dried again, obtains CA/CW-1 sponge dressing.
Specific embodiment 9: present embodiment is unlike specific embodiment eight: to the calcium alginate sea of crosslinking
The H of 1/5~1/4 times of sodium alginate soln volume in silk floss2S donor compound CW-1 solution.Other and specific embodiment eight
It is identical.
Specific embodiment 10: present embodiment is unlike specific embodiment eight: to the calcium alginate sea of crosslinking
The H of 1/5 times of sodium alginate soln volume in silk floss2S donor compound CW-1 solution.It is other identical as specific embodiment eight.
The content of present invention is not limited only to the content of the respective embodiments described above, the group of one of them or several specific embodiments
The purpose of invention also may be implemented in contract sample.
Beneficial effects of the present invention are verified by following embodiment:
Embodiment 1
Sulfa drugs with P-aminobenzene-sulfonamide structure is the artificial synthesized antimicrobial of the first kind, for clinical existing
More than 80 years.Sulfanilamide structure is connected to H2One end of S donor compound, can be in release H2Generating after S gas molecule has antibacterial
Active by-product.
The present embodiment devises the H based on intramolecular cyclization2S donor compound, the structure adjust molecule inner ring by pH
Change the efficiency of activation, to generate the H of efficient pH control2S release.
A kind of H can be used for dressing for skin of the present embodiment2The preparation method of S donor compound, it is according to following step
Suddenly it carries out:
Under the conditions of argon gas protection, 0 DEG C, to the anhydrous methylene chloride of phenyl phosphinylidyne dichloro (0.45mL, 3mmol)
(CH2Cl2, 3.5mL) and 3- hydroxypropionitrile (0.2mL, 3mmol) and triethylamine (0.45mL, 3mmol) are added in solution；Reaction solution exists
Continue after 0 DEG C of reaction 15min in room temperature reaction 3h；Then, 6- (to acetamido benzsulfamide)-L- is added into reaction system
Lysine methyl ester (1.178g, 3.3mmol), triethylamine (1.25mL, 9mmol) and the anhydrous CH of 3.5mL2Cl2Mixed solution, after
Continuous reaction 3h；After the reaction was completed, the CH of 10mL is added thereto2Cl2, and with the 2M H of 10mL2SO4Washing, MgSO4It is dry, most
After be concentrated under reduced pressure；Gained crude product obtains yellow oily intermediate product by chromatography；Later, to the methanol of intermediate product
The LiOH solution newly prepared is added in solution, is concentrated after stirring 12h at room temperature；Obtained solid is resuspended in anhydrous methanol, through 0.2
μm Teflon membrane filtration, then concentrated freeze-dried target product (white solid, H2S donor compound CW-1).
The H of the present embodiment2S donor compound CW-1 synthetic route chart is as shown in Figure 1.
The CW-1 of the present embodiment occurs protonation under the conditions of neutral or subacidity pH and forms mercaptan, and then by nucleophilic carboxyl
Attack occurs intramolecular cyclization and forms five-membered ring by-product while discharging H2S (release H2The schematic diagram of S is as shown in Figure 2).Pass through inspection
It surveys CW-1 under condition of different pH and discharges H2The case where S, finds (as shown in Figure 3), which can be in faintly acid pH (pH 5 and pH
6) a large amount of H of quick release under the conditions of2S, H within 5 minutes2The burst size of S is up to 90%, with the extension of time, the H of high concentration2S
Gas can be escaped from liquid, after 90 min H2S concentration only Yus 50%.Under the conditions of neutral pH (pH 7.4), CW-1 can delay
Slowly H is constantly discharged2S, after 90 min H2The burst size of S is up to 50%.And under the conditions of alkalescent pH (pH 8), CW-1 is only released
Put the H of trace2S.This H regulated and controled by pH of CW-12S delivery mode makes it in physiological conditions being capable of controlled release H2S activity
Molecule, therefore there are specific biological applications.
To the H of the present embodiment2The antibacterial characteristics and biocompatibility of S donor compound CW-1 are tested, specific as follows:
Select staphylococcus aureus (S.aureus) and Escherichia coli (E.coli) respectively as gram-positive bacteria with
The representative of Gram-negative bacteria, to detect CW-1 release H2Antibiotic property (testing result such as Fig. 4 and Fig. 5 institute of by-product after S
Show).
The growth inhibition ratio of S.aureus and E.coli is sent out by the CW-1 that micropore gradient dilution method detects various concentration
Existing, after culture 18 hours, the CW-1 of 8mM can inhibit 80% E.coli bacterial growth respectively and 60% S.aureus bacterium is raw
It is long.It is worth noting that, CW-1 is essentially identical to the inhibiting rate of bacterium under the conditions of pH 6.0 and pH 7.4.Although 6.0 He of pH
H under the conditions of pH 7.42The release characteristics of S are different, but pass through culture in 18 hours, the H of the two2S burst size tends to be close, institute
The amount of by-products of generation is close, therefore does not have significant difference to the inhibition efficiency of bacterium.Result explanation, CW-1 discharge H2S's
By-product has certain antibacterial action due to sulfanilamide structure.
L929 l cell is selected to study the biocompatibility of CW-1 as model cell.It co-cultures 24 hours
After find, CW-1 concentration does not have any cytotoxicity (as shown in Figure 6) to L929 in 1mM or less, this show CW-1 have it is good
Good biocompatibility.
Embodiment 2
A kind of sponge dressing of the present embodiment, follows the steps below:
Firstly, the sodium alginate aqueous solution that mass concentration is 1%, 1.5% and 2% is separately added into mold appropriate,
Sodium alginate sponge is prepared by freeze-drying；Then distinguished using the calcium chloride solution that concentration is 0.2M, 0.5M and 1.0M
Usage ratio to select optimal sodium alginate and calcium chloride, (optimal alginic acid are crosslinked to sodium alginate sponge
Sodium water solution mass concentration is 1.5%, calcium chloride solution concentration 0.2M), by washing, freeze-drying obtains crosslinking again
Calcium alginate sponge (CA sponge).H is added dropwise into CA sponge2S donor compound CW-1 solution (50 mM), is freeze-dried again
Obtain CA/CW-1 sponge dressing.
The present invention includes H2H in the sponge dressing of the calcium alginate of S donor compound CW-12The release of S has good
PH responsiveness, with the reduction of pH value, discharges H in dressing under the conditions of 5.0,6.0,7.4,8.0 pH2The ability of S gradually increases
Add.Compared with free CW-1 molecule, the CW-1 loaded in CA/CW-1 sponge dressing can extend H2Release time of S and increase
H2The burst size of S plays long-time controllable delivery H2The purpose of S.Since the pH value of wound location is acidity, there is pH to ring
The CA/CW-1 dressing of answering property gradually can specifically discharge H to wound location with the absorption of sepage2S, while being provided for wound
Good Moist healing environment and antibacterial action.
Using the wound healing promoting ability of mouse full thickness skin damage model detection CA/CW-1 sponge dressing (such as Fig. 7 institute
Show): from the point of view of the wound healing situation after detection, compared with simple CA dressing, releasable H2The CA/CW-1 dressing of S can be obvious
Accelerate the speed of wound healing.It is found by Histological section, the wound location of CA/CW-1 dressing group forms thicker granulation group
Knit, more keratin positive cell and higher collagen expression quantity, newly-generated corium are completely embedded with tissue,
It is filled with sufficient hair follicle, and along with a large amount of Collagen fiber deposition.And CA dressing group then formed relatively thin granulation tissue layer,
Less keratoprotein positive cell and less collagenous fibres.In addition, CA/CW-1 dressing group shows higher CD31
Expression illustrates H2S can promote the formation and maturation of vascularization.The above result shows that compared with CA dressing, CA/CW-1
Dressing is by discharging H in wound location2S promote the formation of wound granulation tissue, wound epithelialization, collagen deposition and
Vascularization, the final healing rate for accelerating wound.
Claims (10)
1. a kind of H that can be used for dressing for skin2S donor compound, it is characterised in that its chemical structural formula are as follows:
2. preparing a kind of H that can be used for dressing for skin as described in claim 12The method of S donor compound, it is characterised in that
It is followed the steps below:
One, under the conditions of argon gas protection, 0 DEG C, 3- hydroxyl is added into the anhydrous methylene chloride solution of phenyl phosphinylidyne dichloro
Propionitrile and triethylamine obtain reaction solution after mixing；Wherein, 3- hydroxypropionitrile, triethylamine, phenyl phosphinylidyne dichloro and dichloro
The molar ratio of methane is 1:1:1:18~19；
Two, reaction solution continues after 0 DEG C of reaction 15min in room temperature reaction 3h；
Three, be added into obtained reaction system after step 2 reaction 6- (to acetamido benzsulfamide)-L-lysine methyl esters,
The mixed solution of triethylamine and anhydrous methylene chloride, the reaction was continued 3h；Wherein, 6- (to acetamido benzsulfamide)-L- relies ammonia
The molar ratio of sour methyl esters, triethylamine and anhydrous methylene chloride is 1.1:3:18~19；
Four, methylene chloride is added in the solution after step 3 reaction, and successively uses 2M H2SO4Washing, MgSO4It is dry, finally
It is concentrated under reduced pressure, obtains crude product；Wherein, the volume ratio of the solution after methylene chloride is reacted with step 3 is 1:1；
Five, crude product is obtained into yellow oily intermediate product by chromatography, is added into the methanol solution of intermediate product
The LiOH solution newly prepared is concentrated after stirring 12h at room temperature；The volume ratio of the methanol solution of LiOH solution and intermediate product is 1:
1；
Six, the solid after step 5 being concentrated, is resuspended in anhydrous methanol, through 0.2 μm of Teflon membrane filtration, is then concentrated
Freeze-drying, obtains H2S donor compound CW-1, the as H that can be used for dressing for skin2S donor compound.
3. a kind of H that can be used for dressing for skin according to claim 22The preparation method of S donor compound, feature exist
In phenyl phosphinylidyne dichloro anhydrous methylene chloride solution concentration be 0.76M.
4. a kind of H that can be used for dressing for skin according to claim 22The preparation method of S donor compound, feature exist
In LiOH solution concentration be 1M.
5. a kind of H that can be used for dressing for skin according to claim 22The preparation method of S donor compound, feature exist
In 3- hydroxypropionitrile, triethylamine, phenyl phosphinylidyne dichloro and methylene chloride molar ratio be 1:1:1:18.2.
6. a kind of H that can be used for dressing for skin according to claim 22The preparation method of S donor compound, feature exist
In 6- (to acetamido benzsulfamide)-L-lysine methyl esters, triethylamine and anhydrous methylene chloride molar ratio be 1.1:3:
18.2。
7. a kind of sponge dressing, it is characterised in that it is the H for including claim 2 preparation2The alginic acid of S donor compound CW-1
The sponge dressing of calcium.
8. a kind of preparation method of sponge dressing, it is characterised in that it is followed the steps below:
Firstly, the sodium alginate aqueous solution that mass percentage is 1~2% is added in mold, it is prepared by freeze-drying
Sodium alginate sponge；
Then, sodium alginate sponge is crosslinked using the calcium chloride solution that concentration is 0.2~1.0M, by washing, again
Freeze-drying obtains the calcium alginate sponge of crosslinking；
Finally, H prepared by the claim 2 that concentration is 50mM is added dropwise into the calcium alginate sponge of crosslinking2S donor compound CW-
1 solution, is freeze-dried again, obtains CA/CW-1 sponge dressing.
9. a kind of preparation method of sponge dressing according to claim 8, it is characterised in that the calcium alginate sea of crosslinking
The H of 1/5~1/4 times of sodium alginate soln volume in silk floss2S donor compound CW-1 solution.
10. a kind of preparation method of sponge dressing according to claim 8, it is characterised in that the calcium alginate sea of crosslinking
The H of 1/5 times of sodium alginate soln volume in silk floss2S donor compound CW-1 solution.
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| US8541396B2 (en) * | 2009-04-24 | 2013-09-24 | National University Of Singapore | Morpholin-4-ium 4 methoxyphenyl (morpholino) phosphinodithioate (GYY4137) as a novel vasodilator agent |
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