CN105999358A - Method for preparing slow-release antibacterial dressing - Google Patents
Method for preparing slow-release antibacterial dressing Download PDFInfo
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- CN105999358A CN105999358A CN201610568961.1A CN201610568961A CN105999358A CN 105999358 A CN105999358 A CN 105999358A CN 201610568961 A CN201610568961 A CN 201610568961A CN 105999358 A CN105999358 A CN 105999358A
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- preparation
- bacterial cellulose
- sustained
- release antibacterial
- mixed liquor
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- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 68
- 238000000034 method Methods 0.000 title claims abstract description 20
- 229920002749 Bacterial cellulose Polymers 0.000 claims abstract description 92
- 239000005016 bacterial cellulose Substances 0.000 claims abstract description 92
- 229920001661 Chitosan Polymers 0.000 claims abstract description 63
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 59
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 87
- 150000003839 salts Chemical group 0.000 claims description 72
- 238000002360 preparation method Methods 0.000 claims description 63
- 239000007788 liquid Substances 0.000 claims description 58
- 238000003756 stirring Methods 0.000 claims description 53
- 239000012153 distilled water Substances 0.000 claims description 52
- 238000013268 sustained release Methods 0.000 claims description 51
- 239000012730 sustained-release form Substances 0.000 claims description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 43
- 239000000243 solution Substances 0.000 claims description 39
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 29
- 229920002674 hyaluronan Polymers 0.000 claims description 29
- 229960003160 hyaluronic acid Drugs 0.000 claims description 29
- 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 28
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
- 239000000661 sodium alginate Substances 0.000 claims description 28
- 235000010413 sodium alginate Nutrition 0.000 claims description 28
- 229940005550 sodium alginate Drugs 0.000 claims description 28
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 20
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 20
- 229940126864 fibroblast growth factor Drugs 0.000 claims description 20
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 19
- 102000013275 Somatomedins Human genes 0.000 claims description 19
- 239000001110 calcium chloride Substances 0.000 claims description 19
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 19
- 230000010261 cell growth Effects 0.000 claims description 19
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 18
- 239000003102 growth factor Substances 0.000 claims description 17
- 230000001954 sterilising effect Effects 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 15
- 238000004108 freeze drying Methods 0.000 claims description 14
- 238000007710 freezing Methods 0.000 claims description 14
- 230000008014 freezing Effects 0.000 claims description 14
- 239000004568 cement Substances 0.000 claims description 11
- 239000002131 composite material Substances 0.000 claims description 11
- LXFDOQZJJZHUSM-UHFFFAOYSA-M benzyl-(2-dodecylphenyl)-diphenylphosphanium chloride Chemical compound [Cl-].C(CCCCCCCCCCC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC1=CC=CC=C1 LXFDOQZJJZHUSM-UHFFFAOYSA-M 0.000 claims description 8
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 6
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 6
- 210000005167 vascular cell Anatomy 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 239000012266 salt solution Substances 0.000 claims description 4
- NBHIUODBAZGNRC-UHFFFAOYSA-M [Cl-].C(CCCCCCCCCCCCC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC1=CC=CC=C1 Chemical compound [Cl-].C(CCCCCCCCCCCCC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC1=CC=CC=C1 NBHIUODBAZGNRC-UHFFFAOYSA-M 0.000 claims description 3
- DCUNPGMILKYBPR-UHFFFAOYSA-M [Cl-].C(CCCCCCCCCCCCCCC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC1=CC=CC=C1 Chemical compound [Cl-].C(CCCCCCCCCCCCCCC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC1=CC=CC=C1 DCUNPGMILKYBPR-UHFFFAOYSA-M 0.000 claims description 3
- NSIFOGPAKNSGNW-UHFFFAOYSA-M dodecyl(triphenyl)phosphonium bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCCCCCCC)C1=CC=CC=C1 NSIFOGPAKNSGNW-UHFFFAOYSA-M 0.000 claims description 3
- UXMZNEHSMYESLH-UHFFFAOYSA-M hexadecyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCCCCCCCCCCC)C1=CC=CC=C1 UXMZNEHSMYESLH-UHFFFAOYSA-M 0.000 claims description 3
- FUMBGFNGBMYHGH-UHFFFAOYSA-M triphenyl(tetradecyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCCCCCCCCC)C1=CC=CC=C1 FUMBGFNGBMYHGH-UHFFFAOYSA-M 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 16
- 239000000463 material Substances 0.000 abstract description 9
- 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 abstract description 8
- 229940072056 alginate Drugs 0.000 abstract description 8
- 235000010443 alginic acid Nutrition 0.000 abstract description 8
- 229920000615 alginic acid Polymers 0.000 abstract description 8
- 206010052428 Wound Diseases 0.000 abstract description 7
- 208000027418 Wounds and injury Diseases 0.000 abstract description 7
- 238000004132 cross linking Methods 0.000 abstract description 7
- 230000029663 wound healing Effects 0.000 abstract description 7
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 241000894006 Bacteria Species 0.000 abstract description 2
- 238000011068 loading method Methods 0.000 abstract description 2
- 150000004714 phosphonium salts Chemical class 0.000 abstract 2
- 230000009977 dual effect Effects 0.000 abstract 1
- 230000023597 hemostasis Effects 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 238000004321 preservation Methods 0.000 abstract 1
- 238000009423 ventilation Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- 238000005406 washing Methods 0.000 description 20
- 239000003814 drug Substances 0.000 description 13
- 230000003578 releasing effect Effects 0.000 description 6
- 230000003115 biocidal effect Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000025 haemostatic effect Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 241000191967 Staphylococcus aureus Species 0.000 description 4
- 229940030225 antihemorrhagics Drugs 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 239000004599 antimicrobial Substances 0.000 description 3
- 210000000416 exudates and transudate Anatomy 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 230000003020 moisturizing effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010068052 Mosaicism Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002364 anti-haemorrhagic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920003086 cellulose ether Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000000589 cicatrix Anatomy 0.000 description 1
- -1 compound calcium chloride Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000008104 plant cellulose Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 210000003765 sex chromosome Anatomy 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L15/18—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
-
- 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
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
- A61L2300/208—Quaternary ammonium compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of medical dressings, and discloses a method for preparing a slow-release antibacterial dressing. The method comprises the following steps: loading a phosphonium salt on bacterial cellulose, and wrapping the bacterial cellulose loaded with the phosphonium salt, and functional assistant materials by quaternary ammonium salt chitosan and alginate after multi-crosslinking. The slow-release antibacterial dressing has a dual slow-release antibacterial function, is capable of killing and inhibiting bacteria for a long time, and has multiple effects of moisture preservation, ventilation, wound percolate absorption, rapid hemostasis, wound healing promotion and the like.
Description
Technical field
The present invention relates to medical dressing field, be specifically related to the preparation method of a kind of sustained-release antibacterial dressing.
Background technology
Traditional dressing operational efficiency is relatively low, need to frequently change, and has certain zest to skin.The slow-release material superior function in drug release application aspect is demonstrated in a large number in recent years about medicament slow release basic research and clinical treatment.In order to improve therapeutic effect, reduce untoward reaction and change number of times, meeting the requirements such as efficient, long-acting, toxic and side effects is low, slow release dressing can be used.Slow release dressing be pharmaceutically active molecule is combined with macromolecule carrier (or compound, encapsulation) after, throwing passes through the control modes such as diffusion, infiltration in being applied to biological activity body, pharmaceutically active molecule discharges with suitable concentration and persistent period again, thus reaches to give full play to the purpose of curative effect of medication.The feature of slow release dressing is by the effective control to drug medical dosage, it is possible to reduces the toxic and side effects of medicine, reduces Drug resistance, improves stability and the effective rate of utilization of medicine.The targeted of medicine can also be realized, subtract replacing number of times, alleviate the misery of patient, and human and material resources and financial resources etc. can be saved.
The natural macromolecular material being usually used in excipient substance field at present has starch, gelatin, chitosan, cellulose ether etc., and their mechanism of action and using method are not quite similar, and releasing effect also has difference.Starch extensively apply with in tablet medicine, play a part adhesive, disintegrating agent and filler, in drug release process, combine moisture and strengthen the stability of medicine, and in slow releasing preparation, play the effect of Drug controlled release speed, but owing to its moisture absorption is reunited, the shortcomings such as poor fluidity so that it is application has limitation.Gelatin forms slow release layer by cross-linking reaction, can better control over the release behavior of medicine thus be widely used, but it is poor as sustained release performance during small-molecule drug carrier.Chitosan is present in a kind of natural macromolecular material in the cell wall of Crustaceans, fungus and plant, has good biocompatibility, but the most unsatisfactory as excipient substance effect in terms of medicine controlled releasing by chitosan.Therefore, development function is various, and the slow release dressing of superior performance is a big focus of current medical dressing research field.
Bacterial cellulose is similar to plant cellulose structure, is all the macromolecular compound being formed by connecting with β-Isosorbide-5-Nitrae glycosidic bond by glucose, is a kind of natural organic high-molecular.Bacterial cellulose has porous superfine nanometer three-dimensional net structure, has higher biocompatibility and biodegradability, and water absorption, specific retention and tensile strength are high.The nanoscale of Bacterial cellulose is mesoporous can be used as " template ", this template has high biocompatibility and good biodegradability, and performance and the Modulatory character of structure during templated synthesis, other macromolecule, organic or inorganic molecule are combined for matrix with this template, the new function material with excellent properties can be obtained.
Quaternary Ammonium Salt of Chitosan is the product of chitosan quaternary ammonium, and electropositive is stronger than chitosan, and anti-microbial property is higher than chitosan.But in the face of the most serious infection, general Quaternary Ammonium Salt of Chitosan curative effect owes ideal, and quaternary ammonium salt antibacterial is faced with increasing bacterial resistance sex chromosome mosaicism simultaneously.Therefore, it is necessary to add other types antibacterial to strengthen Quaternary Ammonium Salt of Chitosan entirety antibacterial effect to tackle the most serious infection.
Quaternary salt is that a class is similar to quaternary ammonium salt structure, and antibacterial effect more preferably antibacterial.Quaternary salt has efficiently, wide spectrum, bactericidal action, but quaternary salt is as a kind of organic molecule antibacterial, and deficiency maximum in application process is that the antibacterial persistent period is short.The present invention uses Bacterial cellulose as the matrix material of slow release dressing, little for quaternary salt molecule antibacterial is loaded on Bacterial cellulose by the mode first with chemical load, utilizing the three-dimensional manometer network structure of Bacterial cellulose, slow releasing function is played in the release to quaternary salt；Simultaneously, cross-linking with alginate in conjunction with Quaternary Ammonium Salt of Chitosan, embedded by the Bacterial cellulose of load quaternary salt, the slow release for quaternary salt provides dual-sustained-release carrier, the sustained-release antibacterial dressing prepared has dual-sustained-release antibacterial action, overcomes the defect that the antibacterial timeliness of pure quaternary salt is short.The sustained-release antibacterial dressing of preparation not only has the multi-efficiencies such as slow delivery of antimicrobials, sterilization, moisturizing, ventilative, absorbing wound exudate, also has quick-acting haemostatic powder, promotes the effects such as wound healing.
Summary of the invention
It is an object of the invention to solve defect of the prior art, it is provided that the preparation method of a kind of sustained-release antibacterial dressing.Preparation process of the present invention is simple, easy to operate, utilizes the mode of chemical load to load on Bacterial cellulose by little for quaternary salt molecule antibacterial, utilizes the three-dimensional manometer network structure of Bacterial cellulose, and slow releasing function is played in the release to quaternary salt；Simultaneously, cross-linking with alginate in conjunction with Quaternary Ammonium Salt of Chitosan, embedded by the Bacterial cellulose of load quaternary salt, the slow release for quaternary salt provides dual-sustained-release carrier, the sustained-release antibacterial dressing prepared has dual-sustained-release antibacterial action, overcomes the defect that the antibacterial timeliness of pure quaternary salt is short.The sustained-release antibacterial dressing of preparation has slow delivery of antimicrobials simultaneously, has persistently sterilization, a biocidal property, moisturizing, ventilative, absorbing wound exudate, quick-acting haemostatic powder, promotion wound healing etc. multi-efficiency.
For achieving the above object, technical scheme is as follows:
The preparation method of a kind of sustained-release antibacterial dressing, described preparation method specifically comprises the following steps that
(1) preparation of quaternary salt/Bacterial cellulose: Bacterial cellulose first carries out Low Temperature Plasma Treating, and treated Bacterial cellulose is dissolved in aqueous isopropanol, adds quaternary salt solution, stirring, cools down, washs, dries, obtain quaternary salt/Bacterial cellulose；
(2) preparation of mixed liquor A: Quaternary Ammonium Salt of Chitosan is dissolved in distilled water, stir, it is configured to Quaternary Ammonium Salt of Chitosan solution, add calcium chloride, it is subsequently adding quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) preparation of mixed liquid B: sodium alginate, glycerol, somatomedin, hyaluronic acid are added in distilled water and stir, forms mixed liquid B；
(4) preparation of mixed liquor C: mixed liquor A prepared by step (2) joined in mixed liquid B prepared by step (3), and stir, then carries out ice-bath ultrasonic process, and ultrasonic time is 2～4h, obtains mixed liquor C；
(5) preparation of sustained-release antibacterial dressing: mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, then proceeds in freezer dryer, lyophilization 48h, take out cut, pack, sterilizing, obtain sustained-release antibacterial dressing.
Further, the concretely comprising the following steps of Low Temperature Plasma Treating in described step (1): carrying out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, and vacuum is 150Pa, the time that processes under room temperature is 1min-2min.
Further, in described step (1), the percentage by weight of aqueous isopropanol is 60wt%～80wt%, and the percentage by weight of quaternary salt solution is 5.0wt%～8.0wt%, and whipping temp is 40～50 DEG C, and mixing time is 8～12h, and drying temperature is 70 DEG C.
Preferably, in described step (1), Bacterial cellulose is 4:1 with the mass ratio of quaternary salt.
Preferably, in described step (2), the percentage by weight of Quaternary Ammonium Salt of Chitosan solution is 2.0wt%～4.0wt%, and Quaternary Ammonium Salt of Chitosan is 10:1 with the mass ratio of calcium chloride, and Quaternary Ammonium Salt of Chitosan is 4:1～6:1 with the mass ratio of quaternary salt/Bacterial cellulose.
Further, mixed liquid B prepared by described step (3) by parts by weight based on, by constituting as follows:
Sodium alginate
2～4 parts,
Glycerol
1～2 part,
Somatomedin
0.05～0.1 part,
Hyaluronic acid
0.05～0.1 part,
Distilled water
20～40 parts.
Preferably, described somatomedin is made up of at least one in epithelical cell growth factor, the vascular cell growth factor, fibroblast growth factor (FGF) and platelet-derived growth factor.
Preferably, in described step (4), mixed liquor A is that 1:1 mixes with mixed liquid B according to volume ratio.
Preferably, in described step (5), the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, and the cryogenic temperature of freezer dryer is-80 DEG C.
Preferably, described quaternary salt is the one in dodecyl benzyltriphenylphosphonium chloride, dodecyl triphenyl phosphonium bromide, myristyl benzyltriphenylphosphonium chloride, myristyl triphenyl phosphonium bromide, cetyl benzyltriphenylphosphonium chloride, cetyl triphenyl phosphonium bromide.
The invention have the benefit that
(1) present invention uses Low Temperature Plasma Treating Bacterial cellulose, the surface of reactivated bacteria cellulose, improves its reactivity.In low-temperature plasma bulk electric field, Bacterial cellulose surface produces active group and aoxidizes in atmosphere, generates-CO-,-OH2The groups such as O-, and then cause quaternary salt and Bacterial cellulose to carry out chemical graft reaction.Lower temperature plasma technology is simple to operate, is not required to use initiator, and does not affect the performance of Bacterial cellulose body.
(2) little for the quaternary salt of Long carbon chain molecule antibacterial is loaded on Bacterial cellulose by the present invention, makes full use of the three-dimensional manometer network structure of Bacterial cellulose, and the quaternary salt loaded on Bacterial cellulose plays the effect of slowly release；Simultaneously, cross-link with alginate in conjunction with Quaternary Ammonium Salt of Chitosan, the Bacterial cellulose of load quaternary salt is embedded, slow release for quaternary salt provides dual-sustained-release carrier, the dressing prepared has dual-sustained-release antibacterial action, overcome the defect that the antibacterial timeliness of pure quaternary salt is short so that quaternary salt is slowly released, there is durable antibiotic, biocidal efficacies.
(3) present invention is in preparation sustained-release antibacterial application procedures, Quaternary Ammonium Salt of Chitosan crosslinks with alginate, the functional auxiliary material such as glycerol, somatomedin, hyaluronic acid have been embedded simultaneously, these functional auxiliary material and quaternary salt antibacterial synergism, can promote wound healing, makes wound keep moistening, gnotobasis, accelerate wound bonding, promote that granulation is formed, shorten wound-healing cycle, and effectively reduce the generation of cicatrix.
(4) the sustained-release antibacterial dressing that prepared by the present invention, possibly together with anti-hemorrhagic compound calcium chloride, condensable wound blood, reaches the effect of quick-acting haemostatic powder.Meanwhile, the emulsifying environment that calcium chloride is formed when utilizing mixing in preparation method, strengthen the effect of Quaternary Ammonium Salt of Chitosan and alginate cross-linking reaction, promote to crosslink reaction, reach to embed the effect of quaternary salt/Bacterial cellulose and other functional auxiliary material simultaneously.
Accompanying drawing explanation
Fig. 1 is that in embodiment 8, the bacteriostasis rate of staphylococcus aureus is detected figure in different times of contact by experimental group and matched group 1 ~ 5.
Detailed description of the invention
Below in conjunction with embodiment, technical scheme is described further.
Embodiment
1
The preparation method of a kind of sustained-release antibacterial dressing, described preparation method specifically comprises the following steps that
(1) Bacterial cellulose first carrying out Low Temperature Plasma Treating, carry out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 1min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 60wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the dodecyl benzyltriphenylphosphonium chloride solution that 10g percentage by weight is 5.0wt%, 40 DEG C of stirring 12h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；
(2) 2g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.2g calcium chloride, stir, it is subsequently adding 0.5g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 2 parts, glycerol 1 part, epithelical cell growth factor 0.05 part, hyaluronic acid 0.05 part, distilled water 20 parts composition；
(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 2h, obtains mixed liquor C；
(5) mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, taking-up is cut, is packed, sterilizing, obtains sustained-release antibacterial dressing.
Embodiment
2
The preparation method of a kind of sustained-release antibacterial dressing, described preparation method specifically comprises the following steps that
(1) Bacterial cellulose first carrying out Low Temperature Plasma Treating, carry out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 1min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 60wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the dodecyl benzyltriphenylphosphonium chloride solution that 10g percentage by weight is 5.0wt%, 40 DEG C of stirring 12h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；
(2) 2g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.2g calcium chloride, stir, it is subsequently adding 0.5g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 2 parts, glycerol 1 part, epithelical cell growth factor 0.05 part, fibroblast growth factor (FGF) 0.05 part, hyaluronic acid 0.05 part, distilled water 20 parts composition；
(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 2h, obtains mixed liquor C；
(5) mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, taking-up is cut, is packed, sterilizing, obtains sustained-release antibacterial dressing.
Embodiment
3
The preparation method of a kind of sustained-release antibacterial dressing, described preparation method specifically comprises the following steps that
(1) Bacterial cellulose first carrying out Low Temperature Plasma Treating, carry out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 1min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 65wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the myristyl benzyltriphenylphosphonium chloride solution that 8.3g percentage by weight is 6.0wt%, 40 DEG C of stirring 12h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；
(2) 2g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.2g calcium chloride, stir, it is subsequently adding 0.5g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 3 parts, glycerol 1.5 parts, epithelical cell growth factor 0.05 part, the vascular cell growth factor 0.05 part, hyaluronic acid 0.05 part, distilled water 20 parts composition；
(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 2h, obtains mixed liquor C；
(5) mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, taking-up is cut, is packed, sterilizing, obtains sustained-release antibacterial dressing.
Embodiment
4
The preparation method of a kind of sustained-release antibacterial dressing, described preparation method specifically comprises the following steps that
(1) Bacterial cellulose first carrying out Low Temperature Plasma Treating, carry out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 1.5min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 70wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the cetyl benzyltriphenylphosphonium chloride solution that 7.1g percentage by weight is 7.0wt%, 45 DEG C of stirring 11h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；
(2) 3g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.3g calcium chloride, stir, it is subsequently adding 0.6g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 3 parts, glycerol 1 part, epithelical cell growth factor 0.05 part, platelet-derived growth factor 0.05 part, hyaluronic acid 0.05 part, distilled water 30 parts composition；
(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 3h, obtains mixed liquor C；
(5) mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, taking-up is cut, is packed, sterilizing, obtains sustained-release antibacterial dressing.
Embodiment
5
The preparation method of a kind of sustained-release antibacterial dressing, described preparation method specifically comprises the following steps that
(1) Bacterial cellulose first carrying out Low Temperature Plasma Treating, carry out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 1.5min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 75wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the dodecyl triphenyl phosphonium bromide solution that 7.1g percentage by weight is 7.0wt%, 45 DEG C of stirring 10h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；
(2) 3g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.3g calcium chloride, stir, it is subsequently adding 0.5g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 2 parts, glycerol 1.5 parts, epithelical cell growth factor 0.05 part, platelet-derived growth factor 0.05 part, hyaluronic acid 0.1 part, distilled water 30 parts composition；
(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 3h, obtains mixed liquor C；
(5) mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, taking-up is cut, is packed, sterilizing, obtains sustained-release antibacterial dressing.
Embodiment
6
The preparation method of a kind of sustained-release antibacterial dressing, described preparation method specifically comprises the following steps that
(1) Bacterial cellulose first carrying out Low Temperature Plasma Treating, carry out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 2min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 80wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the myristyl triphenyl phosphonium bromide solution that 6.3g percentage by weight is 8.0wt%, 50 DEG C of stirring 9h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；
(2) 4g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.4g calcium chloride, stir, it is subsequently adding 0.8g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by sodium alginate 4 parts, glycerol 2 parts, epithelical cell growth factor 0.025 part by weight, the vascular cell growth factor 0.025 part, fibroblast growth factor (FGF) 0.025 part, platelet-derived growth factor 0.025 part, hyaluronic acid 0.08 part, distilled water 40 parts composition；
(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 4h, obtains mixed liquor C；
(5) mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, taking-up is cut, is packed, sterilizing, obtains sustained-release antibacterial dressing.
Embodiment
7
The preparation method of a kind of sustained-release antibacterial dressing, described preparation method specifically comprises the following steps that
(1) Bacterial cellulose first carrying out Low Temperature Plasma Treating, carry out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 2min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 80wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the cetyl triphenyl phosphonium bromide solution that 6.3g percentage by weight is 8.0wt%, 50 DEG C of stirring 8h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；
(2) 4g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.4g calcium chloride, stir, it is subsequently adding 1.0g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by sodium alginate 4 parts, glycerol 1.8 parts, epithelical cell growth factor 0.025 part by weight, the vascular cell growth factor 0.025 part, fibroblast growth factor (FGF) 0.025 part, platelet-derived growth factor 0.025 part, hyaluronic acid 0.1 part, distilled water 40 parts composition；
(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 4h, obtains mixed liquor C；
(5) mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, taking-up is cut, is packed, sterilizing, obtains sustained-release antibacterial dressing.
The sustained-release antibacterial dressing obtaining embodiment 1 ~ 7 carries out antibacterial tests and animal experiment analysis, and result is as shown in the table:
As can be seen from the above table, sustained-release antibacterial dressing prepared by the present invention has good antibacterial effect, has good haemostatic effect, energy wound healing simultaneously, shortens healing time.
Embodiment
8
Experimental group: using embodiment 2 as experimental group.
Matched group 1
Preparation method specifically comprises the following steps that (1) weighs 2g Bacterial cellulose and is dissolved in the aqueous isopropanol that 100mL percentage by weight is 60wt%, add the dodecyl benzyltriphenylphosphonium chloride solution that 10g percentage by weight is 5.0wt%, 40 DEG C of stirring 12h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；(2) 2g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.2g calcium chloride, stir, it is subsequently adding 0.5g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 2 parts, glycerol 1 part, epithelical cell growth factor 0.05 part, fibroblast growth factor (FGF) 0.05 part, hyaluronic acid 0.05 part, distilled water 20 parts composition；(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 2h, obtains mixed liquor C；(5) mixed liquor C prepared by step (4) being placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator be-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, and taking-up is cut, packed, sterilizing, obtains dressing a.
Matched group 2
Preparation method specifically comprises the following steps that (1) weighs 2g Quaternary Ammonium Salt of Chitosan, it is dissolved in 100mL distilled water, it is configured to Quaternary Ammonium Salt of Chitosan solution, add 0.2g calcium chloride, stir, it is subsequently adding the dodecyl benzyltriphenylphosphonium chloride solution that 10g percentage by weight is 5.0wt%, and is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；(2) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 2 parts, glycerol 1 part, epithelical cell growth factor 0.05 part, fibroblast growth factor (FGF) 0.05 part, hyaluronic acid 0.05 part, distilled water 20 parts composition；(3) mixed liquor A prepared by step (1) being joined in mixed liquid B prepared by step (2), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 2h, obtains mixed liquor C；(4) mixed liquor C prepared by step (3) being placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator be-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, and taking-up is cut, packed, sterilizing, obtains dressing b.
Matched group 3
Preparation method specifically comprises the following steps that (1) weighs 2g Quaternary Ammonium Salt of Chitosan, is dissolved in 100mL distilled water, is configured to Quaternary Ammonium Salt of Chitosan solution, adds 0.2g calcium chloride, stirs, and forms mixed liquor A；(2) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 2 parts, glycerol 1 part, epithelical cell growth factor 0.05 part, fibroblast growth factor (FGF) 0.05 part, hyaluronic acid 0.05 part, distilled water 20 parts composition；(3) mixed liquor A prepared by step (1) being joined in mixed liquid B prepared by step (2), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 2h, obtains mixed liquor C；(4) mixed liquor C prepared by step (3) being placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator be-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, and taking-up is cut, packed, sterilizing, obtains dressing c.
Matched group 4
Preparation method specifically comprises the following steps that Bacterial cellulose is first carried out Low Temperature Plasma Treating by (1), carries out Cement Composite Treated by Plasma in air atmosphere, and the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 1min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 60wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the dodecyl benzyltriphenylphosphonium chloride solution that 10g percentage by weight is 5.0wt%, 40 DEG C of stirring 12h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；(2) measure 100mL distilled water, add 0.2g calcium chloride, stir, be subsequently adding 0.5g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in solution, form mixed liquor A；(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 2 parts, glycerol 1 part, epithelical cell growth factor 0.05 part, fibroblast growth factor (FGF) 0.05 part, hyaluronic acid 0.05 part, distilled water 20 parts composition；(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 2h, obtains mixed liquor C；(5) mixed liquor C prepared by step (4) being placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator be-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, and taking-up is cut, packed, sterilizing, obtains dressing d.
Matched group 5
Preparation method specifically comprises the following steps that Bacterial cellulose is first carried out Low Temperature Plasma Treating by (1), carries out Cement Composite Treated by Plasma in air atmosphere, and the voltage of plasma is 140V, and vacuum is 150Pa, and the time that processes under room temperature is 1min；Weigh 2g and be dissolved in the aqueous isopropanol that 100mL percentage by weight is 60wt% through the Bacterial cellulose of Low Temperature Plasma Treating, add the dodecyl benzyltriphenylphosphonium chloride solution that 10g percentage by weight is 5.0wt%, 40 DEG C of stirring 12h, then cool down, first with washing with acetone, finally use distilled water cyclic washing, dry under the conditions of 70 DEG C, obtain quaternary salt/Bacterial cellulose；(2) 2g Quaternary Ammonium Salt of Chitosan is weighed, it is dissolved in 100mL distilled water, is configured to Quaternary Ammonium Salt of Chitosan solution, be subsequently adding 0.5g quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；(3) sodium alginate, glycerol, somatomedin, hyaluronic acid added in distilled water and stir, forming mixed liquid B；The mixed liquid B of preparation is counted by weight by sodium alginate 2 parts, glycerol 1 part, epithelical cell growth factor 0.05 part, fibroblast growth factor (FGF) 0.05 part, hyaluronic acid 0.05 part, distilled water 20 parts composition；(4) mixed liquor A prepared by step (2) being joined in mixed liquid B prepared by step (3), mix with volume ratio 1:1 of mixed liquid B according to mixed liquor A, and stir, then carry out ice-bath ultrasonic, ultrasonic time is 2h, obtains mixed liquor C；(5) mixed liquor C prepared by step (4) being placed in refrigerator freezing 24h, the cryogenic temperature of refrigerator be-15 ~ 0 DEG C, then proceeds to freezer dryer lyophilization 48h, and the cryogenic temperature of freezer dryer is-80 DEG C, and taking-up is cut, packed, sterilizing, obtains dressing e.
The dressing obtaining the experimental group in the present embodiment and matched group 1 ~ 5 carries out sustained-release antibacterial agent detection, and different times of contact are as shown in the table to the bacteriostasis rate testing result of staphylococcus aureus:
| 0h | 4h | 8h | 18h | 24h | 36h | 48h | 72h | |
| Experimental group | 92.2% | 94.2% | 96.3% | 99.0% | 99.2% | 99.5% | 99.7% | 99.8% |
| Matched group 1 | 72.2% | 73.8% | 75.1% | 78.4% | 78.8% | 78.8% | 78.2% | 77.8% |
| Matched group 2 | 93.6% | 96.8% | 98.4% | 96.2% | 94.2% | 90.3% | 86.7% | 79.5% |
| Matched group 3 | 70.9% | 71.5% | 72.8% | 72.1% | 72.2% | 72.1% | 71.9% | 70.6% |
| Matched group 4 | 90.5% | 92.2% | 94.0% | 95.8% | 95.6% | 93.7% | 91.0% | 87.7% |
| Matched group 5 | 92.7% | 95.4% | 97.5% | 97.9% | 98.2% | 98.2% | 96.2% | 94.0% |
As seen from the above table, matched group 1 because of Bacterial cellulose not through Low Temperature Plasma Treating so that it is only having loaded a small amount of quaternary salt, its anti-microbial property of prepared dressing is substantially reduced.Matched group 2 is not because loading to quaternary salt on Bacterial cellulose, therefore quaternary salt is released at short notice, and in 8h, the bacteriostasis rate to staphylococcus aureus is rapidly reached 98.4%, and after 8h, its bacteriostasis rate reduces, and reduces rapidly after 24h；Experimental group has, because of Bacterial cellulose, the effect slowly discharged to quaternary salt, and the bacteriostasis rate of staphylococcus aureus is gradually increased by it, and when 72h, bacteriostasis rate still can reach 99.8%, shows long-acting antibiotic property；Therefore due to the slow releasing function of Bacterial cellulose, dressing shows lasting antibacterial activity.Matched group 3, because not adding quaternary salt/Bacterial cellulose in dressing, is mainly shown relatively low anti-microbial property by Quaternary Ammonium Salt of Chitosan.Matched group 4, because not adding Quaternary Ammonium Salt of Chitosan, occurs being gradually lowered during the bacteriostasis rate 24h of dressing, but the amplitude of reduction is little, the crosslinking embedding effect not having Quaternary Ammonium Salt of Chitosan and alginate be described, it is impossible to collaborative Bacterial cellulose realizes dual-sustained-release effect.Matched group 5 is not because adding calcium chloride, and dressing bacteriostasis rate occurs being gradually lowered when 48h, but the amplitude of reduction is less, illustrates that calcium chloride can strengthen the effect of Quaternary Ammonium Salt of Chitosan and alginate crosslinking when mixing.
As fully visible, sustained-release antibacterial dressing prepared by the present invention has dual-sustained-release antibacterial action, overcomes the defect that the antibacterial timeliness of pure quaternary salt is short.There is slow delivery of antimicrobials simultaneously, there is persistently sterilization, biocidal property, moisturizing, ventilative, absorbing wound exudate, quick-acting haemostatic powder, promotion wound healing etc. multi-efficiency.
Obviously, the above embodiment of the present invention is only for clearly demonstrating example of the present invention, and is not the restriction to embodiments of the present invention；For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description, here without also cannot all of embodiment be given exhaustive；All any amendment, equivalent and improvement etc. made within the spirit and principles in the present invention, within should be included in the protection domain of the claims in the present invention.
Claims (10)
1. the preparation method of a sustained-release antibacterial dressing, it is characterised in that described preparation method specifically comprises the following steps that
(1) preparation of quaternary salt/Bacterial cellulose: Bacterial cellulose first carries out Low Temperature Plasma Treating, and treated Bacterial cellulose is dissolved in aqueous isopropanol, adds quaternary salt solution, stirring, cools down, washs, dries, obtain quaternary salt/Bacterial cellulose；
(2) preparation of mixed liquor A: Quaternary Ammonium Salt of Chitosan is dissolved in distilled water, stir, it is configured to Quaternary Ammonium Salt of Chitosan solution, add calcium chloride, it is subsequently adding quaternary salt/Bacterial cellulose prepared by step (1), and quaternary salt/Bacterial cellulose is evenly spread in Quaternary Ammonium Salt of Chitosan solution, form mixed liquor A；
(3) preparation of mixed liquid B: sodium alginate, glycerol, somatomedin, hyaluronic acid are added in distilled water and stir, forms mixed liquid B；
(4) preparation of mixed liquor C: mixed liquor A prepared by step (2) joined in mixed liquid B prepared by step (3), and stir, then carries out ice-bath ultrasonic process, and ultrasonic time is 2～4h, obtains mixed liquor C；
(5) preparation of sustained-release antibacterial dressing: mixed liquor C prepared by step (4) is placed in refrigerator freezing 24h, then proceeds in freezer dryer, lyophilization 48h, take out cut, pack, sterilizing, obtain sustained-release antibacterial dressing.
The preparation method of a kind of sustained-release antibacterial dressing the most according to claim 1, it is characterized in that, the concretely comprising the following steps of Low Temperature Plasma Treating in described step (1): carry out Cement Composite Treated by Plasma in air atmosphere, the voltage of plasma is 140V, vacuum is 150Pa, and the time that processes under room temperature is 1min-2min.
The preparation method of a kind of sustained-release antibacterial dressing the most according to claim 1, it is characterized in that, in described step (1), the percentage by weight of aqueous isopropanol is 60wt%～80wt%, the percentage by weight of quaternary salt solution is 5.0wt%～8.0wt%, whipping temp is 40～50 DEG C, mixing time is 8～12h, and drying temperature is 70 DEG C.
The preparation method of a kind of sustained-release antibacterial dressing the most according to claim 1, it is characterised in that in described step (1), Bacterial cellulose is 4:1 with the mass ratio of quaternary salt.
The preparation method of a kind of sustained-release antibacterial dressing the most according to claim 1, it is characterized in that, in described step (2), the percentage by weight of Quaternary Ammonium Salt of Chitosan solution is 2.0wt%～4.0wt%, Quaternary Ammonium Salt of Chitosan is 10:1 with the mass ratio of calcium chloride, and Quaternary Ammonium Salt of Chitosan is 4:1～6:1 with the mass ratio of quaternary salt/Bacterial cellulose.
The preparation method of a kind of sustained-release antibacterial dressing the most according to claim 1, it is characterised in that mixed liquid B prepared by described step (3) by parts by weight based on, by constituting as follows:
Sodium alginate
2～4 parts,
Glycerol
1～2 part,
Somatomedin
0.05～0.1 part,
Hyaluronic acid
0.05～0.1 part,
Distilled water
20～40 parts.
The preparation method of a kind of sustained-release antibacterial dressing the most according to claim 6, it is characterized in that, described somatomedin is made up of at least one in epithelical cell growth factor, the vascular cell growth factor, fibroblast growth factor (FGF) and platelet-derived growth factor.
The preparation method of a kind of sustained-release antibacterial dressing the most according to claim 1, it is characterised in that in described step (4), mixed liquor A is that 1:1 mixes with mixed liquid B according to volume ratio.
The preparation method of a kind of sustained-release antibacterial dressing the most according to claim 1, it is characterised in that in described step (5), the cryogenic temperature of refrigerator is-15 ~ 0 DEG C, and the cryogenic temperature of freezer dryer is-80 DEG C.
10. according to the preparation method of a kind of sustained-release antibacterial dressing described in any one of claim 1-9, it is characterized in that, described quaternary salt is the one in dodecyl benzyltriphenylphosphonium chloride, dodecyl triphenyl phosphonium bromide, myristyl benzyltriphenylphosphonium chloride, myristyl triphenyl phosphonium bromide, cetyl benzyltriphenylphosphonium chloride, cetyl triphenyl phosphonium bromide.
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