CN107266610A - The application of guanidinated chitosan derivative and nanoparticle - Google Patents
The application of guanidinated chitosan derivative and nanoparticle Download PDFInfo
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- CN107266610A CN107266610A CN201710622821.2A CN201710622821A CN107266610A CN 107266610 A CN107266610 A CN 107266610A CN 201710622821 A CN201710622821 A CN 201710622821A CN 107266610 A CN107266610 A CN 107266610A
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- chitosan
- guanidine radicals
- guanidinated
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- 229920001661 Chitosan Polymers 0.000 title claims abstract description 80
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 27
- 239000003181 biological factor Substances 0.000 claims abstract description 12
- 230000035876 healing Effects 0.000 claims abstract description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 47
- 238000006243 chemical reaction Methods 0.000 claims description 46
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 45
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 45
- 229960004198 guanidine Drugs 0.000 claims description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000003368 amide group Chemical group 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 8
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 238000010792 warming Methods 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 5
- 239000003495 polar organic solvent Substances 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 5
- 102000004877 Insulin Human genes 0.000 claims description 4
- 108090001061 Insulin Proteins 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 229930003316 Vitamin D Natural products 0.000 claims description 4
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 4
- 229960000789 guanidine hydrochloride Drugs 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229940125396 insulin Drugs 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims description 4
- 235000019166 vitamin D Nutrition 0.000 claims description 4
- 239000011710 vitamin D Substances 0.000 claims description 4
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 4
- 229940046008 vitamin d Drugs 0.000 claims description 4
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- 238000000502 dialysis Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000019832 sodium triphosphate Nutrition 0.000 claims description 2
- 238000006277 sulfonation reaction Methods 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 206010052428 Wound Diseases 0.000 abstract description 24
- 208000027418 Wounds and injury Diseases 0.000 abstract description 24
- 230000000694 effects Effects 0.000 abstract description 8
- 230000029663 wound healing Effects 0.000 abstract description 6
- 230000001408 fungistatic effect Effects 0.000 abstract description 4
- 230000000717 retained effect Effects 0.000 abstract description 4
- 230000037311 normal skin Effects 0.000 abstract description 3
- 239000012620 biological material Substances 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 14
- 241000700159 Rattus Species 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 8
- 229910001868 water Inorganic materials 0.000 description 8
- 150000002357 guanidines Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 229910021642 ultra pure water Inorganic materials 0.000 description 6
- 239000012498 ultrapure water Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- -1 kanamycins compound Chemical class 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000003385 bacteriostatic effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000460 chlorine Chemical group 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 229930003427 Vitamin E Natural products 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 239000012901 Milli-Q water Substances 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005374 membrane filtration Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- VITPICOSHHCBFU-UHFFFAOYSA-N 1-sulfonylguanidine Chemical compound NC(=N)N=S(=O)=O VITPICOSHHCBFU-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Chemical group 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- 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
-
- 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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/624—Nanocapsules
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Materials For Medical Uses (AREA)
Abstract
The present invention relates to the application of a kind of guanidinated chitosan derivative and nanoparticle, it is related to technical field of biological material.The present invention proposes guanidinated chitosan derivative as the application of bio-carrier, and bioactivity is high, and fungistatic effect is good, and rate of release of the control biotic factor in wound can be realized when transporting the biotic factor with bioactivity as carrier.Application of the nanoparticle of the guanidinated chitosan wrapping biological factor in terms of healing of wound, nanoparticle includes above-mentioned guanidinated chitosan derivative, and biotic factor, the guanidinated chitosan derivative wrapping biological factor, the bioactivity and stability for the biotic factor that can be effectively retained, with good promotion Wound healing activity and wound bacteriostasis, wound healed completely at 23 days, the skin color that wound is newly formed at 27 days is close to normal skin tone, using safety, side effect will not be carried out to skin tape.
Description
Technical field
The present invention relates to technical field of biological material, and more particularly to a kind of guanidinated chitosan derivative and nanoparticle should
With.
Background technology
Chitosan is that the chitin being widely present in nature is obtained through deacetylation, with non-toxic, bio-compatible
Many excellent biological natures such as property and biodegradability.It has now been found that chitosan is carried in antibacterial, pharmaceutical carrier, gene
The fields such as body have boundless prospect.
The multiple compounds of guanidine radicals modification are found to have the amino quilt in good bacteriostatic activity, kanamycins compound
After guanidine radicals modification, bacteriostatic activity there occurs obvious enhancing.Chitosan is coupled after guanidine radicals by a variety of connection arms, antibacterial
Activity has obtained different degrees of lifting.
The content of the invention
It is an object of the invention to provide a kind of application of guanidinated chitosan derivative as bio-carrier, its biology is living
Property it is high, fungistatic effect is good, can realize control biotic factor in wound when transporting the biotic factor with bioactivity as carrier
Rate of release.
Another object of the present invention is to provide a kind of nanoparticle of the guanidinated chitosan wrapping biological factor in healing to hinder
Application in terms of mouthful, the bioactivity and stability of the biotic factor that can be effectively retained, with good promotion wound healing
Activity and wound bacteriostasis, using safety, will not carry out side effect to skin tape.
The present invention is solved its technical problem and realized using following technical scheme.
The present invention proposes guanidinated chitosan derivative as the application of bio-carrier, wherein, guanidinated chitosan derives
The chemical structural formula of thing is as follows：
Wherein, R is selected from any of hydrogen or halogen.
M and n is any non-zero natural number.
The present invention proposes a kind of application of nanoparticle of the guanidinated chitosan wrapping biological factor in terms of healing of wound, its
Including above-mentioned guanidinated chitosan derivative, and biotic factor, the guanidinated chitosan derivative wrapping biological factor.
The beneficial effect of the application of the guanidinated chitosan derivative and nanoparticle of the embodiment of the present invention is：
Guanidinated chitosan derivative, its activity is high, and fungistatic effect is good, and can be transported as carrier with bioactivity
Biotic factor, while realizing the speed of control release biotic factor.And the less stable of biotic factor, but the nanoparticle
The bioactivity and stability for the biotic factor that can be effectively retained, while showing good biocidal property and promoting wound to be cured
Close, wound is average to heal completely at 23 days, and the skin color that wound is newly formed at 27 days uses peace close to normal skin tone
Entirely, side effect will not be carried out to skin tape.
Brief description of the drawings
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be attached to what is used required in embodiment
Figure is briefly described, it will be appreciated that the following drawings illustrate only certain embodiments of the present invention, therefore is not construed as pair
The restriction of scope, for those of ordinary skill in the art, on the premise of not paying creative work, can also be according to this
A little accompanying drawings obtain other related accompanying drawings.
The structural representation of the nanoparticle for the guanidinated chitosan wrapping biological factor that Fig. 1 provides for the present invention；
Fig. 2 is the N that the embodiment of the present invention 1 and 2 is provided ,-Boc the guanidines of N '-two1HNMR spectrograms and molecular formula；
Fig. 3 is the N ,-Boc-N of N '-two that the embodiment of the present invention 1 and 2 is provided "-trimethyl fluoride sulfonyl guanidine1HNMR spectrograms and
Molecular formula；
Fig. 4 is the FTIR spectrograms of N- (N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyls dimethyl-silicon-chitosan and divided
Minor；
Fig. 5 is the FTIR spectrograms and molecular formula of N- guanidine radicals chitosans；
Fig. 6 is CG, CGNP1 and CGNP2 scanning electron microscope diagram piece.
Embodiment
, below will be in the embodiment of the present invention to make the purpose, technical scheme and advantage of the embodiment of the present invention clearer
Technical scheme be clearly and completely described.Unreceipted actual conditions person, builds according to normal condition or manufacturer in embodiment
The condition of view is carried out.Agents useful for same or the unreceipted production firm person of instrument, are the conventional production that can be obtained by commercially available purchase
Product.
The application to the guanidinated chitosan derivative and nanoparticle of the embodiment of the present invention is specifically described below.
The present invention provides guanidinated chitosan derivative as the application of bio-carrier, the guanidinated chitosan derivative
Chemical structural formula is as follows：
Wherein, R is selected from any of hydrogen or halogen；For example, R is hydrogen, fluorine, chlorine, bromine or iodine, do not limit herein.
Wherein, m and n is any non-zero natural number, such as m/n=0.01,0.05,0.1,0.5,1,2,5,50 or 100,
Wherein m is different from n ratio, ultimately results in bacteriostatic activity difference, and this area staff can be had according to actual situation
The m and n of body ratio selection.
The guanidinated chitosan derivative is as carrier, and its activity is high, and fungistatic effect is good, and can transport tool as carrier
There is the biotic factor of bioactivity, while the speed of control release biotic factor can also be realized, make drug effect optimal.
In the present invention, guanidinated chitosan derivative is prepared by following methods：
Guanidine hydrochloride is mixed with inorganic base in organic reagent, adds after amido protecting group and reacts, obtain the first guanidine radicals sample
Product；N1 and N2 in wherein the first sample are protected by amino protecting group.
Preferably, after inorganic base mixing, 2~10min is stirred at room temperature, guanidine hydrochloride is sufficiently mixed with inorganic base, carries
High reaction efficiency.
Preferably, 30-60 DEG C of reaction is warming up to after adding amido protecting group, it is highly preferred that being warming up to 30~50 DEG C instead
Should, such as 30 DEG C, 35 DEG C, 40 DEG C, 45 DEG C or 50 DEG C effectively facilitate reaction efficiency.
Preferably, 48~72h is stirred, it is highly preferred that 50~60h of stirring, accelerates reaction rate, effectively save the time.
Preferably, organic reagent is DMF, dimethyl sulfoxide (DMSO) or dichloromethane, and solubility is high, and not
Reacted with other reagents.
Preferably, inorganic base is NaOH, KOH, K2CO3、Na2CO3Or NaHCO3Deng, it is alkaline moderate, it is easy to reaction.
It is highly preferred that amino protecting group is phthalyl, tertiary butyl oxycarbonyl (Boc), tablet held before the breast by officials methoxycarbonyl group (Fmoc),
On the one hand it is easy to early stage to protect amino, is on the other hand easy to the later stage to remove.
Meanwhile, using thin-layer chromatography (TLC) detection reaction until reaction is complete, the achievements conversion rate of reaction is effectively improved,
Make full use of each raw material.Preferably, the N1 obtained completely and the protected first guanidine radicals samples of N2 crude product will be reacted through separation
Purifying obtains the protected first guanidine radicals samples of N1 and N2, and its purity is high, is easy to post-production.
First guanidine radicals sample is dissolved in after polar organic solvent and activated by organic base, precooling adds sulphonic acid anhydride sulfonation anti-
Should, the second guanidine radicals sample is obtained, wherein the N1 and N2 in the second guanidine radicals sample are protected.
Wherein, organic base is triethylamine or pyridine, and activation efficiency is high.
Because sulphonic acid anhydride is acid very strong, murther is reacted under normal temperature, it is therefore necessary to be added dropwise after cooling, it is preferable that pre-
It is cooled to -40~-80 DEG C, such as -40 DEG C, -45 DEG C, -50 DEG C, 60 DEG C or -80 DEG C.It is highly preferred that being cooled to -65~-80 DEG C, example in advance
Such as -65 DEG C, -70 DEG C, -75 DEG C or -80 DEG C.
Because temperature is too low, sulfonating reaction is very slow, can hardly carry out, therefore need to carry out heating up before sulfonating reaction, preferably
Ground, be warming up under normal temperature condition react, it is highly preferred that 2~10h of sulfonating reaction, such as 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h or
10h etc., it is highly preferred that 3~6h of sulfonating reaction, it is preferable that TLC trace points plate detection reaction, until reaction completely, is effectively improved
The achievements conversion rate of reaction, makes full use of each raw material.Preferably, the N1, N2 and the N3 that are obtained after the completion of sulfonating reaction are protected
The guanidine derivative crude product of shield obtains N1 through isolating and purifying, N2 and the protected guanidine derivatives of N3, and its purity is high, after being easy to
Phase processes, and effectively improves the quality of final products.
The chitosan of hydroxyl protection is dissolved with polar organic solvent, and is activated after the amido of chitosan, the second guanidine radicals is added
Sample, is preferable over reaction under conditions of room temperature, obtains guanidinated chitosan sample.
Wherein, the amido of chitosan is activated by alkali, alkali is pyridine, triethylamine, NaHCO3Or Na2CO3, effective activation shell
The amido of glycan, improves the reaction efficiency of chitosan and the second guanidine radicals sample.
Finally, the protection group in the protection group and chitosan on removing guanidine radicals, dialysis is lyophilized, produces.Wherein, using acid or
Alkali removes the protection group on guanidine radicals and chitosan skeleton, this area staff can be selected according to actual conditions suitable acid or
Alkali, then this does not do specific restriction.
Preferably, the product that guanidine radicals sample sulfonating reaction is obtained carries out halogen aminating reaction, introduces a halogen into, obtains the second guanidine radicals
Sample.
It is highly preferred that the product that guanidine radicals sample sulfonating reaction is obtained and NaClO solution, such as the NaClO solution of pH=7
Halogen aminating reaction.
Wherein, pH=7 NaClO solution has following methods preparation：The NaClO aqueous solution is adjusted to pH=using sulfuric acid
7, add after the second guanidine radicals sample, the second guanidine radicals sample is completely dissolved and is produced more bubble, then in the bar of room temperature
Magnetic agitation reacts at least 1h under part, and system is diluted with water after completing in reaction, then dialysis 2 days, lyophilized to obtain the 3rd guanidine radicals
Sample.
The present invention also provides a kind of application of nanoparticle of the guanidinated chitosan wrapping biological factor in terms of healing of wound,
Wherein, the structural representation of the nanoparticle of the guanidinated chitosan wrapping biological factor is as shown in figure 1, wherein, what big spheroid was represented
It is nanoparticle prepared by guanidinated chitosan, what the different spherula of multiple color was represented in ball is various variety classeses and not
With the biotic factor of content.
The nanoparticle of the guanidinated chitosan wrapping biological factor includes above-mentioned guanidinated chitosan derivative, and biological
The factor, wherein the guanidinated chitosan derivative wrapping biological factor.Wherein, above-mentioned guanidinated chitosan can live biotic factor
Property it is high, while retaining guanidine radicals chitosan derivatives good activity, protect the bioactivity of load biotic factor.
Preferably, biotic factor includes at least one of vitamin C, vitamin D, vitamin E or insulin, for example, give birth to
The thing factor includes vitamin C, or vitamin D, or biotic factor include vitamin E and insulin, or biotic factor includes dimension
Raw element C, vitamin D, vitamin E and insulin etc..
Above-mentioned guanidinated chitosan wrapping biological factor nanoparticle is prepared by following methods：Guanidinated chitosan is derived
Thing, biotic factor are in reaction under the catalytic action of sodium tripolyphosphate.Although the less stable of biotic factor, passes through this method
The bioactivity and stability for the biotic factor that can be effectively retained, while shortening preparation time.
Preferably, the catalytic reaction is carried out under conditions of 0~30 DEG C, preferably stirs 30min~3h.Effectively improve reaction
Efficiency.The feature and performance to the present invention are described in further detail with reference to embodiments.
Embodiment 1
1. N, the preparation of-Boc guanidines of N '-two
Clean three-necked flask is taken, 200mg KOH and 265mg Na is weighed2CO3Be put into flask, plus 50mL DMSO,
Stir at room temperature.Weigh 239mg guanidine hydrochlorides and add flask, stirring 5min is completely dissolved.Weigh 1.528g (Boc)2O is added
In flask, 40 DEG C, stirring reaction 60h are warming up to.After reaction is finished, with 500mL H2O disperses, and produces substantial amounts of white solid
Body, collected by suction solid.Silica gel column chromatography obtains N ,-Boc guanidine the sterlings of N '-two, its1HNMR spectrograms and molecular formula are as shown in Figure 2.
2. the preparation of the N ,-Boc-N of N '-two "-trimethyl fluoride sulfonyl guanidines
Weigh 0.3g the N ,-Boc guanidines of N '-two, with 25mL CH2Cl2Dissolving, plus 168 μ L triethylamine, be placed on single port burning
In bottle, -78 DEG C are pre-chilled to.203 μ L trifluoromethyl sulfonic acid anhydride is measured, with 25mL CH2Cl2Dissolving, is used under the conditions of -78 DEG C
The low liquid funnel of constant pressure is added drop-wise in single-necked flask, and used time about 1h, system becomes pale red.Take out, stir at room temperature after dripping off
4h is reacted, after reaction is finished, stops stirring, with 2mol/L NaHSO4The aqueous solution washs CH2Cl2Mutually twice, each 20mL,
Again with milli-Q water twice, each 20mL.The CH of system after washing2Cl2Solution anhydrous Na2SO4It is dried overnight, takes out
Filter is obtained containing the N ,-Boc-N of N '-two " system of-trifluoromethane sulfonic acid guanidine, silica gel column chromatography obtains sterling, its1HNMR spectrograms and
Molecular formula is as shown in Figure 3.
3. the preparation of N- (N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyls dimethyl-silicon-chitosan
3, the 6-O- di-t-butyls dimethyl-silicon-chitosan for weighing 1g is added in single-necked flask, then adds 50mL CH2Cl2
As solvent, in the triethylamine addition system for measuring 2.15mL, stir and evenly mix.Weigh 1.02g the N ,-Boc-N of N '-two "-trifluoro
Sulfonyloxy methyl guanidine is added in beaker, is stirred at room temperature, and 48h is stirred at room temperature.After reaction is finished, dialysed with ultra-pure water,
Then freeze and obtain light yellow solid, its FTIR spectrogram and molecular formula are as shown in Figure 4.
4. the preparation of N- guanidine radicals chitosan (CG)
N- (N, the N-Boc of '-two guanidine radicals) -3, the 6-O- di-t-butyls dimethyl-silicon-chitosan for weighing 0.5g is put into single port
In flask, plus 100mL methanol is stirred and evenly mixed, and is pre-chilled to 0 DEG C.13.4mL HCl is measured, single port is added drop-wise to constant pressure funnel
In flask, used time 30min.After completion of dropping, ice-water bath is removed, room temperature reaction 48h is returned to.After having reacted, 1mol/ is used
The L NaOH aqueous solution adjusts pH value to 6, is then dialysed and is freezed with ultra-pure water, obtains white solid product, its FTIR spectrogram
And molecular formula is as shown in Figure 5.
5. the preparation of CG wrapping biological actives factor nanoparticle (CGNP).
The CG for weighing 0.1g is dissolved with 100mL water, adds bioactie agent.A small amount of TPP is weighed, is dissolved to water
10mg/mL, is then added dropwise 13.3mL TPP into system, stirring reaction 1h at room temperature with constant pressure funnel.With 0.22 μm
Aqueous phase membrane filtration, freezes after being dialysed with ultra-pure water and obtains CGNP.Specifically, the bioactie agent added by control
Amount is different, prepares CGNP1 and CGNP2.CG, CGNP1 and CGNP2 scanning electron microscope diagram piece are as shown in Figure 6.According to Fig. 6,
It will be evident that CGNP1 and CGNP2 is because being loaded with bioactie agent, particle becomes big, and compatibility is good.
Embodiment 2
1. N, the preparation of-Boc guanidines of N '-two
Clean three-necked flask is taken, 200mg KOH and 265mg Na is weighed2CO3Be put into flask, plus 50mL DMSO,
Stir at room temperature.The guanidine hydrochloride for weighing 239mg adds flask, and stirring 5min is completely dissolved.Weigh 1.528g (Boc)2O
Add in flask, be warming up to 40 DEG C, stirring reaction 60h.After reaction is finished, with 500mL H2O disperses, and produces substantial amounts of white
Color solid, collected by suction solid.Silica gel column chromatography obtains N ,-Boc guanidine the sterlings of N '-two, its1HNMR spectrograms and molecular formula such as Fig. 1
It is shown.
2. the preparation of the N ,-Boc-N of N '-two "-trimethyl fluoride sulfonyl guanidines
Weigh 0.3g the N ,-Boc guanidines of N '-two, with 25mL CH2Cl2Dissolving, plus 168 μ L triethylamine, be placed on single port burning
In bottle, -78 DEG C are pre-chilled to.203 μ L trifluoromethyl sulfonic acid anhydride is measured, with 25mL CH2Cl2Dissolving, is used under the conditions of -78 DEG C
The low liquid funnel of constant pressure is added drop-wise in single-necked flask, and used time about 1h, system becomes pale red.Take out, stir at room temperature after dripping off
4h is reacted, after reaction is finished, stops stirring, with 2mol/L NaHSO4The aqueous solution washs CH2Cl2Mutually twice, each 20mL,
Again with milli-Q water twice, each 20mL.The CH of system after washing2Cl2Solution anhydrous Na2SO4It is dried overnight, takes out
Filter is obtained containing the N ,-Boc-N of N '-two " system of-trifluoromethane sulfonic acid guanidine, silica gel column chromatography obtains sterling, its 1HNMR spectrogram and
Molecular formula is as shown in Figure 2.
3. the preparation of N- (N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyls dimethyl-silicon-chitosan
3, the 6-O- di-t-butyls dimethyl-silicon-chitosan for weighing 1g is added in single-necked flask, then adds 50mLCH2Cl2Make
For solvent, in the mL triethylamine addition systems for measuring 2.15, stir and evenly mix.Weigh 1.02g the N ,-Boc-N of N '-two "-fluoroform
Base sulphonyl guanidine is added in beaker, is stirred at room temperature, and 48h is stirred at room temperature.After reaction is finished, dialysed with ultra-pure water, so
Freeze afterwards and obtain light yellow solid, its FTIR spectrogram and molecular formula are as shown in Figure 3.
4. the preparation of N- halogen amine-N '-(N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyls dimethyl-silicon-chitosan
Clean single-necked flask is taken, 0.5g N- (N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyl dimethyl is added
Silicon-chitosan；Configure the NaClO aqueous solution, and using and using 1N sulfuric acid solution adjust NaClO aqueous solution pH as 7；30mL is taken to prepare
The good NaClO aqueous solution is poured into flask, N- (N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyls dimethyl-silicon-chitosan
It is completely dissolved and produces more bubble, magnetic agitation reacts 1h under conditions of room temperature, body is diluted with water after having reacted
System, the mass concentration for making N- (N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyls dimethyl-silicon-chitosan is 5%.Then thoroughly
Analysis 2 days, it is lyophilized to obtain the 3rd guanidine radicals sample, i.e. N- halogen amine-N '-(N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyl diformazans
Base silicon-chitosan.
5. the preparation of N- halogen amine guanidinated chitosan derivative
Weigh 0.5g N- halogen amine-N '-(N, the N-Boc of '-two guanidine radicals) -3,6-O- di-t-butyls dimethyl-silicon-chitosan
It is put into single-necked flask, plus 100mL methanol is stirred and evenly mixed, and is pre-chilled to 0 DEG C.13.4mL HCl is measured, is dripped with constant pressure funnel
It is added in single-necked flask, used time 30min.After completion of dropping, ice-water bath is removed, room temperature reaction 48h is returned to.It is reacted
Afterwards, pH value is adjusted to 6 with the 1mol/L NaOH aqueous solution, then dialysed and freezed with ultra-pure water, obtain N- halogen amine guanidinated
Chitosan derivatives.
6. the preparation of N- halogen amine guanidinated chitosan derivative wrapping biological active factor nanoparticle.
The N- halogen amine guanidinated chitosan derivative for weighing 0.1g is dissolved with 100mL water, adds suitable bioactivity
The factor.A small amount of TPP is weighed, 10mg/mL is dissolved to water, 13.3mLTPP then is added dropwise into system with constant pressure funnel,
Stirring reaction 1h at room temperature.With 0.22 μm of aqueous phase membrane filtration, freezed after being dialysed with ultra-pure water and obtain nanoparticle.
Embodiment 3
A kind of dressing of promotion wound healing, it includes guanidinated chitosan bag made from embodiment 1 and/or embodiment 2
Wrap up in the nanoparticle of biotic factor.
Test example
Wistar rat wound healing assays
On the day of operation, first with free from worries and Su Mian Xin anesthetized rat, treat that rat goes into a coma completely, will by back with shaver
The hair at the position performed the operation all is shaved off, and is placed on operating table, and the exposed skin in back is wiped with Iodophor.Apart from rat ridge
Left and right sets 2 wounds respectively at post 1cm, and wound size is respectively 1cm × 1cm, and wound depth reaches skin corium.Rats with left
Wound is not added with any medicine, as a control group, Right Wound sample-adding product, is used as experimental group.By rat numbering 1-6.Wherein, No. 1
It is chitosan group with No. 2, No. 3 and No. 4 are CGNP1 groups, and No. 5 and No. 6 are CGNP2 groups.In order to prevent rat from being baited to wound,
Wound is wrapped up with hospital gauze, and is regularly replaced.Gauze is periodically removed after surgery, and the wound of rat is taken pictures, and surveys
Measure the size of wound.Every rat is placed in a cage during experiment, keeps the temperature of Animal House at 25 ± 2 DEG C.
3rd, 4,5, the wound of No. 6 rats is average healed completely at 23 days, the skin color that wound is newly formed at 27 days
Close to normal skin tone, healing rate is significantly higher than chitosan group.
Treatment of wounds is carried out using the nanoparticle provided including embodiment 2, effective rush is similarly obtained compared to chitosan group
Enter the result of the test of wound healing, therefore, the auxiliary material of the offer of release embodiment 3 that can be undoubtedly is same compared to chitosan group
Obtain effectively facilitating wound healing.
To sum up, the guanidinated chitosan derivative of the embodiment of the present invention, nanoparticle and preparation method thereof, prepared by the present invention
Guanidinated chitosan is simple in construction, and reaction time is short, and bacteriostatic activity is preferably, the supported active after being prepared by nanoparticle
The factor, with good bioactivity.
Embodiments described above is a part of embodiment of the invention, rather than whole embodiments.The reality of the present invention
The detailed description for applying example is not intended to limit the scope of claimed invention, but is merely representative of the selected implementation of the present invention
Example.Based on the embodiment in the present invention, what those of ordinary skill in the art were obtained under the premise of creative work is not made
Every other embodiment, belongs to the scope of protection of the invention.
Claims (10)
1. a kind of guanidinated chitosan derivative is used as the application of bio-carrier, it is characterised in that the guanidinated chitosan spreads out
Biological chemical structural formula is as follows：
Wherein, R is selected from any of hydrogen or halogen；
M and n is any non-zero natural number.
2. application according to claim 1, it is characterised in that the guanidinated chitosan derivative is by following methods system
It is standby：
Guanidine hydrochloride is mixed with inorganic base in organic reagent, adds after amido protecting group and reacts, obtain the first guanidine radicals sample；
The first guanidine radicals sample is dissolved in after polar organic solvent and activated by organic base, precooling adds sulphonic acid anhydride sulfonation anti-
Should, obtain the second guanidine radicals sample；
The chitosan of hydroxyl protection is dissolved with polar organic solvent, and is activated after the amido of the chitosan, the second guanidine radicals is added
Example reaction, obtains guanidinated chitosan sample；
The protection group of guanidinated chitosan sample is removed, dialysis is lyophilized, produces；
Preferably, the product that the guanidine radicals sample sulfonating reaction is obtained carries out halogen aminating reaction, obtains the second guanidine radicals sample；
Preferably, the product carries out halogen aminating reaction with NaClO solution and the second guanidine radicals sample is made.
3. application according to claim 2, it is characterised in that the organic reagent is selected from DMF, two
One or more in methyl sulfoxide or dichloromethane；
Preferably, the inorganic base is selected from NaOH, KOH, K2CO3、Na2CO3Or NaHCO3In one or more,
Preferably, add and the obtained first guanidine radicals sample of 30-60 DEG C of reaction is warming up to after amino protecting group.
4. application according to claim 2, it is characterised in that the amino protecting group is phthalyl, the tert-butyl group
Oxygen carbonyl or tablet held before the breast by officials methoxycarbonyl group.
5. application according to claim 2, it is characterised in that the polar organic solvent be chloroform, dichloromethane,
DMF or dimethyl sulfoxide (DMSO)；
Preferably, the organic base is triethylamine or pyridine；
Preferably, after the first guanidine radicals sample is activated through the organic base, -65~-80 DEG C are cooled in advance；
Preferably, adding the sulphonic acid anhydride sulfonating reaction includes：15-35 DEG C is warming up to, 3~6h is reacted.
6. application according to claim 2, it is characterised in that the amido of the chitosan, the alkali choosing are activated by alkali
From pyridine, triethylamine, NaHCO3Or Na2CO3In one or more.
7. a kind of application of nanoparticle of the guanidinated chitosan wrapping biological factor in terms of healing of wound, it is characterised in that institute
Stating nanoparticle includes guanidinated chitosan derivative as claimed in claim 1, and biotic factor, the guanidinated chitosan
Derivative wraps up the biotic factor.
8. application according to claim 7, it is characterised in that the biotic factor includes vitamin C, vitamin D, dimension life
At least one of plain E or insulin.
9. application according to claim 7, it is characterised in that the nanoparticle is prepared by following methods：By the guanidine radicals
Change chitosan derivatives, the biotic factor in reaction under the catalytic action of sodium tripolyphosphate.
10. application according to claim 9, it is characterised in that carried out under conditions of reacting on 0~30 DEG C.
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| CN108682530A (en) * | 2018-04-27 | 2018-10-19 | 熊振 | A kind of water-base magnetic liquid and preparation method thereof |
| CN109925515A (en) * | 2019-03-05 | 2019-06-25 | 上海珑欣生物医学科技有限公司 | For treating microRNA nano-complex and its preparation and the application of colon cancer |
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Application publication date: 20171020 |