CN105816911B - A kind of reparation gel containing growth factor and preparation method thereof - Google Patents
A kind of reparation gel containing growth factor and preparation method thereof Download PDFInfo
- Publication number
- CN105816911B CN105816911B CN201610375170.7A CN201610375170A CN105816911B CN 105816911 B CN105816911 B CN 105816911B CN 201610375170 A CN201610375170 A CN 201610375170A CN 105816911 B CN105816911 B CN 105816911B
- Authority
- CN
- China
- Prior art keywords
- growth factor
- gel
- water
- soluble polymer
- cellulose derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000003102 growth factor Substances 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 229920002678 cellulose Polymers 0.000 claims abstract description 39
- 239000001913 cellulose Substances 0.000 claims abstract description 39
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 33
- 150000004676 glycans Chemical class 0.000 claims abstract description 32
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 30
- 239000005017 polysaccharide Substances 0.000 claims abstract description 30
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 19
- 229960001631 carbomer Drugs 0.000 claims abstract description 19
- 239000008367 deionised water Substances 0.000 claims abstract description 14
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 14
- 230000000149 penetrating effect Effects 0.000 claims abstract description 14
- 229920001577 copolymer Polymers 0.000 claims abstract description 9
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 8
- 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 abstract description 6
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 6
- 230000003750 conditioning effect Effects 0.000 claims abstract description 3
- 235000010980 cellulose Nutrition 0.000 claims description 37
- 229920001661 Chitosan Polymers 0.000 claims description 21
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 18
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 10
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 10
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 10
- 241000196324 Embryophyta Species 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 239000003002 pH adjusting agent Substances 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 239000003292 glue Substances 0.000 claims description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 235000001560 Prosopis chilensis Nutrition 0.000 claims description 6
- 240000007909 Prosopis juliflora Species 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 229920002148 Gellan gum Polymers 0.000 claims description 5
- 239000000216 gellan gum Substances 0.000 claims description 5
- 235000010492 gellan gum Nutrition 0.000 claims description 5
- 230000006798 recombination Effects 0.000 claims description 5
- 238000005215 recombination Methods 0.000 claims description 5
- 229920001285 xanthan gum Polymers 0.000 claims description 5
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 claims description 4
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 4
- 229940116978 human epidermal growth factor Drugs 0.000 claims description 4
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 claims description 4
- 101001052035 Homo sapiens Fibroblast growth factor 2 Proteins 0.000 claims description 3
- 230000033228 biological regulation Effects 0.000 claims description 3
- 235000011187 glycerol Nutrition 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 229920001451 polypropylene glycol Polymers 0.000 claims description 2
- 150000005846 sugar alcohols Polymers 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000003643 water by type Substances 0.000 claims description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims 1
- 229920001046 Nanocellulose Polymers 0.000 claims 1
- 229940031098 ethanolamine Drugs 0.000 claims 1
- 229940126864 fibroblast growth factor Drugs 0.000 claims 1
- 230000008470 skin growth Effects 0.000 claims 1
- 230000001408 fungistatic effect Effects 0.000 abstract description 15
- 231100000241 scar Toxicity 0.000 abstract description 15
- 230000008439 repair process Effects 0.000 abstract description 12
- 239000003814 drug Substances 0.000 abstract description 9
- 230000035876 healing Effects 0.000 abstract description 9
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 230000002265 prevention Effects 0.000 abstract description 5
- 239000000499 gel Substances 0.000 description 75
- 208000027418 Wounds and injury Diseases 0.000 description 38
- 206010052428 Wound Diseases 0.000 description 37
- 210000003491 skin Anatomy 0.000 description 23
- 230000000052 comparative effect Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 13
- 206010053615 Thermal burn Diseases 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 11
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 11
- 239000008108 microcrystalline cellulose Substances 0.000 description 11
- 229940016286 microcrystalline cellulose Drugs 0.000 description 11
- 239000000243 solution Substances 0.000 description 9
- 238000013329 compounding Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000029663 wound healing Effects 0.000 description 6
- 230000006378 damage Effects 0.000 description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 229910052710 silicon Inorganic materials 0.000 description 4
- 239000010703 silicon Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 230000037314 wound repair Effects 0.000 description 4
- 230000003385 bacteriostatic effect Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000013081 microcrystal Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 244000247812 Amorphophallus rivieri Species 0.000 description 2
- 235000001206 Amorphophallus rivieri Nutrition 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 229920002581 Glucomannan Polymers 0.000 description 2
- 206010061217 Infestation Diseases 0.000 description 2
- 229920002752 Konjac Polymers 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 229940046240 glucomannan Drugs 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000000252 konjac Substances 0.000 description 2
- 235000010485 konjac Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 241000588626 Acinetobacter baumannii Species 0.000 description 1
- 241000206575 Chondrus crispus Species 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 1
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 1
- 241000521257 Hydrops Species 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241000406668 Loxodonta cyclotis Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 206010053692 Wound complication Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 230000009172 bursting Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000000205 computational method Methods 0.000 description 1
- 239000004064 cosurfactant Substances 0.000 description 1
- 230000001808 coupling effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001804 debridement Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000000893 fibroproliferative effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000010977 jade Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- -1 methyl Octadecyl Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- HMZGPNHSPWNGEP-UHFFFAOYSA-N octadecyl 2-methylprop-2-enoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)C(C)=C HMZGPNHSPWNGEP-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000003507 refrigerant Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0023—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to field of medicaments, specifically related to a kind of reparation gel containing growth factor and preparation method thereof, including 0.001~0.02% growth factor, 0.05~1% alkaline polysaccharide, 0.5~2% cellulose derivative water-soluble polymer, 0.05~2% natural plant polyose, the natural water-soluble copolymer of 0.01~1% exocellular polysaccharide class, 0.1~2% carbomer, 12~40% NMFs, 0.05~4%pH conditioning agents, 0.01 2% hyaluronic acid, 0.6~3% cutaneous permeable agent, 0.1~0.3% penetrating agent and balance deionized water.The present invention, which repairs gel, has an excellent fungistatic effect, good moisture pick-up properties, and it can significantly improve the cure rate of the surface of a wound and shorten the healing time of the surface of a wound, and be capable of the formation of prevention of scar.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of reparation gel containing growth factor and preparation method thereof.
Background technology
Skin is made up of epidermis, corium and hypodermis, and its function is to protect in-vivo tissue to be damaged from the external world;Carry out new
Old metabolism such as absorbs, perspired, sebum secreted and row rush down waste;Skin can also adjust body temperature, impression pain, tactile, pressure, warm, cold etc.
Stimulate, and have immunization.People in life inevitably by the different wound of various weights, ask its be wound, from
Operation wound is often can hardly be avoided after right disaster and illness.When skin injury reaches to a certain degree, because fibroproliferative is anti-
Should, skin ultrastructure will be come to an end with cicatrization.Various body surface scars can all destroy original skin integrity, damage and hold
Looks, the injury of body and mind is brought to patient.It is always medical science neck that its appearance destruction caused how is treated while wound repair
One of the important subject in domain.
The development of current new pattern compress and application, dermatoplasty, gene therapy, culture cell transplantation and artificial skin grafting dermepenthesis,
The application of Porcine HGF and TCM Therapy all occur in that new technology.Traditional dressing can keep the drying of the surface of a wound well
Property, but can not effectively prevent the surface of a wound from being infected, and easily be sticked together with planing surface, may cause during removal the surface of a wound again by
Damage;New synthesis type dressing has good elasticity and gas permeability, but hygroscopicity is bad, may cause to form hydrops at the surface of a wound
And cause the breeding of bacterium.There is certain repulsion immune response applied to clinical tissue engineering product, therapeutic effect is not good enough.
Based on the defect in traditional wound dressing performance, in recent years, the modern wound dressing of polytype is developed, its
In wound dressing containing growth factor have become medical dressing field development new highlight.It not only overcomes traditional dressing performance
Single shortcoming, and the addition of growth factor also makes dressing add wound healing, improve the work(of wound healing effect
Effect.
Chinese patent application 201410438877.9 discloses a kind of wound repair gel containing hexagonal mesoporous silicon and its system
Preparation Method, the composition of the invention includes:Hexagonal mesoporous silicon, basic fibroblast growth factor FGF-21, chitosan, surface are lived
Property agent, cosurfactant, glycerin monostearate, carbomer, pH adjusting agent and deionized water.The present invention utilizes hexagonal mesoporous
Silicon carrying active substance and active ingredient, can improve its stability, and reach slow release effect;Growth factor can stimulate cell to move
The synthesis of dynamic, merisis and intercellular protein, promotes capillary of skin generation and tissue growth, is conducive to scar repairing;
Chitosan is inhibited to various bacteria, also with good film forming, is conducive to wound healing and hemostasis;This is simultaneously
Glycerin monostearate in system also acts as the effect of skin care.It is, using carbomer as thickener, to be gathered using shell in the invention
Gel is repaired in the growth factor-loaded hexagonal mesoporous silicon formation of sugar parcel, the reparation Growth in Gel factor and glycan substrate it
Between not exclusively run through, growth factor, which is difficult to ooze out, reaches that skin surface repairs skin, and repairing effect is good;Due to carbomer gel
Viscosity it is larger, it is difficult to smear, use feeling is not good.
Therefore, the technical problem existed for above-mentioned prior art, needs a kind of repairing effect of proposition badly notable, it is easy to smear
The reparation gel containing growth factor.
The content of the invention
In order to solve technical problem present in above-mentioned prior art, it is an object of the invention to provide one kind containing growth because
Reparation gel of son and preparation method thereof, the reparation gel has excellent repairing effect and fungistatic effect, good hygroscopicity
Can and it tend to smear out, it can significantly improve the cure rate of the surface of a wound and shorten the healing time of the surface of a wound, and be capable of prevention of scar
Formed.
The invention provides a kind of reparation gel containing growth factor, include the component of following mass percent:0.001~
0.02% growth factor, the growth factor is selected from recombinant human epidermal growth factor and/or recombination human basic fibroblast cell is given birth to
The long factor;
0.05~1% alkaline polysaccharide, the alkaline polysaccharide is selected from chitosan and/or chitosan derivatives;
0.5~2% cellulose derivative water-soluble polymer, the cellulose derivative water-soluble polymer, which is selected from, to be modified
One or more in nano micro crystal cellulose, sodium carboxymethylcellulose and hydroxyethyl cellulose;
0.05~2% natural plant polyose, the natural plant polyose is in konjac glucomannan, carragheen and algaroba glue
It is one or more of;
The natural water-soluble copolymer of 0.01~1% exocellular polysaccharide class, the water-soluble polymerization of the exocellular polysaccharide class
Thing is selected from xanthans or gellan gum;
0.1~2% carbomer;
12~40% NMFs, the NMF is selected from polyalcohols;
0.05~6%pH conditioning agents, the one kind or several of the pH adjusting agent in triethanolamine, citric acid and tartaric acid
Kind;
0.6~6% cutaneous permeable agent, the cutaneous permeable agent is selected from Tween 80 and/or azone;
0.1~0.3% penetrating agent, the one kind or several of the penetrating agent in polyethylene glycol, polypropylene glycol and polyglycereol
Kind;
0.01-2% hyaluronic acids;
40~70% deionized waters.
Preferably, the growth factor is by recombinant human epidermal growth factor and recombination human basic fibroblast growth factor
By 1:0.5~1 weight is than composition.
Preferably, the growth factor is by recombinant human epidermal growth factor and recombination human basic fibroblast growth factor
By 1:1 weight is than composition.
Preferably, the NMF is selected from glycerine.
Preferably, the cellulose derivative water-soluble polymer is by modified Nano microcrystalline cellulose and carboxymethyl cellulose
Sodium presses 1:0.2~0.5 weight is than composition.
Preferably, the cellulose derivative water-soluble polymer is by modified Nano microcrystalline cellulose and carboxymethyl cellulose
Sodium presses 1:0.5 weight is than composition.
Preferably, the natural water-soluble copolymer of the exocellular polysaccharide class presses 1 by xanthans and gellan gum:1~3 weight
Than composition.
Preferably, the natural water-soluble copolymer of the exocellular polysaccharide class presses 1 by xanthans and gellan gum:1.5 weight
Than composition.
Preferably, the pH adjusting agent is selected from triethanolamine.
Preferably, the alkaline polysaccharide is selected from carboxymethyl chitosan, the molecular weight of the carboxymethyl chitosan for 2~4 ×
103, substitution value is 80~90%.
Preferably, the natural plant polyose is selected from algaroba glue.
Preferably, the cutaneous permeable agent is selected from Tween 80.
Preferably, the penetrating agent is selected from polyethylene glycol.
Correspondingly, present invention also offers the preparation method of the above-mentioned reparation gel containing growth factor, it includes following step
Suddenly:
A) take 0.05~1% alkaline polysaccharide to be added in deionized water, be mixed evenly, obtain 0.5~1wt% alkalescence
Polysaccharide solution, takes 0.5~2% cellulose derivative water-soluble polymer to be added in deionized water, is mixed evenly, obtains
0.1~1wt% cellulose derivative water-soluble polymer solution;Above two solution is well mixed, is swelled, alkalescence is obtained
Polysaccharide/cellulose derivative water-soluble polymer support;
B 0.1~2% carbomer) is taken, is added to while stirring in deionized water, 12~24h is swelled, above-mentioned alkalescence is added
Polysaccharide/cellulose derivative water-soluble polymer support, stirs 10~15min, continuously adds 0.05~2% natural plants many
Sugar, the natural water-soluble copolymer of 0.01~1% exocellular polysaccharide class, 12~40% NMFs, 0.6~6% cutaneous permeable agent,
0.01-2% hyaluronic acids and 0.1~0.3% penetrating agent, stir 20~35min, add pH adjusting agent regulation pH be 6.0~
7.0, obtain plural gel;
C) take 0.001~0.02% growth factor to be dissolved in deionized water and be configured to growth factor solution, growth factor is molten
Liquid is added to above-mentioned steps B) gained plural gel in, be well mixed, be stored at room temperature 2~5h, produce.
Alkaline polysaccharide is 2~4 × 10 from molecular weight3, substitution value is 80~90% carboxymethyl chitosan, and it is water-soluble
Height, with preferable antibiotic property, moisture absorbability and moisture retentivity, film forming and biocompatibility, but its antibiotic property and mechanical strength are still
So fail to reach requirement.
Inventor has found to add cellulose derivative water-soluble polymer, is preferably added to modified Nano microcrystalline cellulose and is formed
Carboxymethyl chitosan/cellulose derivative water-soluble polymer support, can be obviously improved carboxymethyl chitosan antibacterial ability and
Mechanical strength.Trace it to its cause and may is that addition cellulose derivative water-soluble polymer can strengthen carboxymethyl chitosan gel
With the interface compatibility of other matrix, and growth factor and carboxymethyl chitosan gel is set to form connect altogether anti-completely through getting up
Bacterium gel, keeps wound to dry.The huge specific surface area of cellulose derivative water-soluble polymer can improve gel and wound
Contact area so that antibacterial effect can be played preferably, and addition cellulose derivative water-soluble polymer can make water-setting
The structure of glue formation is more fluffy, prevents hydrogel in the larger ice crystal of follow-up (- 15 DEG C) generations of freezing by bursting by freezing.
But because the addition of cellulose derivative water-soluble polymer causes the viscosity of gel rapidly to rise, spreading property
Difference, adds carbomer, can neutralize the acidity of carboxymethyl chitosan, stretches its strand disperse and is formed in great swelling state
Gel so that the hydrogel formed is homogeneous, it is easy to smear, no greasy feeling is good with skin and mucosa coupling effect.Three assists
Same synergy, assigns the excellent anti-microbial property of gel, good spreading property.The addition of sodium carboxymethylcellulose causes gel in guarantor
There is preferable hygroscopicity, it can adsorb the surface of a wound and suppurate while holding above-mentioned characteristic, it cooperates with cellulose derivative water-soluble poly
Compound can stablize the drying for keeping the surface of a wound, improve repairing effect.
Hydrogel can further be improved by adding the natural water-soluble copolymer of natural plant polyose and exocellular polysaccharide class
Sense of touch.Because the addition of above-mentioned high molecular polymer makes carbomer-carboxymethyl chitosan-cellulose derivative water-soluble polymer
The viscosity increase of gel, causes moisture holding capacity to rise, the nutritional ingredient inside gel fails to be exuded to up to skin surface, therefore add
Enter penetrating agent penetrating agent, be preferably added to polyethylene glycol, the growth factor of inside can be promoted successfully to be exuded to up to surface of a wound surface hair
The effect of waving, so as to improve the healing time of the surface of a wound.And hyaluronic acid can promote absorption of the skin to growth factor, accelerate to repair
The surface of a wound damages
NMF is added, the healing of wound face can be promoted, the formation of prevention of scar mitigates wound pain.Each component is mutual
Synergistic, forming one has excellent wound repairing ability, an antibacterial ability, the reparation gel of good moisture pick-up properties, and its is easy
In smearing, with control trauma surface infestation, accelerate the effect that wound healing, prevention of scar are formed.
Compared with prior art, reparation gel of the invention has the advantage that:
1) present invention can improve the cure rate of the surface of a wound by repairing gel made from the rational proportion of component, shorten the surface of a wound
Healing time, while avoiding the drawback such as drug resistance, suprainfection, allergic reaction triggered using antibiotic.
2) good hygroscopicity of the present invention, can absorb the diffusate of the surface of a wound, it is allowed to which free gas permeates, while metabolite can lead to
Gel discharge is crossed, and then improves the microenvironment of lesion, promotes the reparation of wound and the surface of a wound.
3) present invention has excellent biocidal property, with control trauma surface infestation, accelerates wound healing, prevention of scar shape
Into effect.
Embodiment:
Below by way of the description of embodiment, the invention will be further described, but this is not the limit to the present invention
System, those skilled in the art are according to the basic thought of the present invention, and various modifications may be made or improves, but without departing from this
The basic thought of invention, within the scope of the present invention.
The embodiment of the present invention 1~7 of table 1 repairs gel component and its consumption (being calculated in mass percent)
Modified Nano microcrystalline cellulose of the present invention is made by following steps:
S1:In the nitration mixture aqueous solution that cellulosic material is added to organic acid and inorganic acid, cellulosic material is in mixed acid liquid
In solid content be 0.05g/mL, in 60 DEG C react 12h, obtain nano micro crystal cellulose suspension;
S2:Above-mentioned suspension is moved into reactor, 5mol ammonium persulfates are added at 90 DEG C, 20min is stirred, weighs methyl
Octadecyl acrylate is soluble in water, is instilled with the drop rate of per second 2 drops in reactor, reacts 6h at 60 DEG C, obtain methyl
The crude product of octadecyl acrylate-nano micro crystal cellulose polymer, wherein octadecyl methacrylate and nanometer
The mol ratio of microcrystalline cellulose is 1:2;
S3:At room temperature toward adding ethyl acetate in above-mentioned crude product, extractive reaction 36h, then rotary evaporation at 50 DEG C
Instrument extracting 80min removes ethyl acetate, obtains modified Nano microcrystalline cellulose.
The embodiment of the present invention 1~7 repairs the preparation method of gel:
A) take alkaline polysaccharide to be added in deionized water, be mixed evenly, obtain alkaline polysaccharide solution, take cellulose to derive
Thing water-soluble polymer is added in deionized water, is mixed evenly, and obtains cellulose derivative water-soluble polymer solution;Will
Above two solution is well mixed, and is swelled, is obtained alkaline polysaccharide/cellulose derivative water-soluble polymer support;
B carbomer) is taken, is added to while stirring in deionized water, 24h is swelled, above-mentioned alkaline polysaccharide/cellulose is added and spreads out
Biological water dissolubility polymer support, stirs 15min, continuously adds natural plant polyose, the water-soluble of exocellular polysaccharide class and gathers
Compound, NMF, cutaneous permeable agent, hyaluronic acid and penetrating agent, stir 30min, and it is 7.0 to add pH adjusting agent regulation pH,
Obtain plural gel;
C) take growth factor to be dissolved in deionized water and be configured to growth factor solution, growth factor solution is added to above-mentioned step
Rapid B) in gained plural gel, it is well mixed, is stored at room temperature 3h, produces.
Comparative example 1, a kind of reparation gel containing growth factor
This comparative example 1 provide a kind of wound repair gel containing growth factor, its by following mass percent component
Composition:0.01% growth factor, 1% carboxymethyl chitosan, 1% modified Nano microcrystalline cellulose, 1% sodium carboxymethylcellulose,
0.05% algaroba glue, 0.05% xanthans, 0.05% gellan gum, 1.5% carbomer, 10% glycerine, 2% triethanolamine, 1%
Hyaluronic acid, 3% Tween 80,0.2% polyethylene glycol and excess water.
Preparation method refers to the preparation method of the embodiment of the present invention 4.
The difference of comparative example 1 and embodiment 4 is:Change modified Nano microcrystalline cellulose and sodium carboxymethylcellulose
Proportioning, specially adds the consumption of sodium carboxymethylcellulose.
Stability test
Example 1~7 and the reparation gel of comparative example 1 are filling in undercoating sealing aluminum pipe, and sealing is placed in 2 DEG C~8
Tested at DEG C, gel is detected respectively at 0th month, 1 month, 3 months, 6 months, 9 months, 12 months, 18 the end of month
Outward appearance, loading amount, pH value, biological activity (%) and total number of bacteria.Testing result is as follows:Embodiment 1~7 and the sample of comparative example 1
Outward appearance, pH, loading amount, total number of bacteria and the biological activity (%) of product meet the requirements within each sealed stage.
Bacteriostatic test
Subjects:The embodiment of the present invention 1~7 and the gained of comparative example 1 repair gel.
Test method:Gel is determined to bacteria to be tested (Escherichia coli, gold using AGP test paper disk method and colony counting method
Staphylococcus aureus, Acinetobacter baumannii, pseudomonas aeruginosa, coagulase-negative staphylococci) fungistatic effect.Prepare
Containing 108The bacteria suspension of/mL bacteria to be tested, is spread evenly across the nutrient agar planar surface of solidification, each μ of flat board 100
L;Gel is aseptically uniformly applied to a diameter of 0.3cm, on the filter paper that sterilizing, drying is crossed, the gel prepared is filtered
The scraps of paper (using sterilizing filter paper piece as blank control) are affixed on the flat board of coated test strain, and scraps of paper repeat number is on each flat board
4, in 37 DEG C of incubated 24h, take contact surface culture to make gradient dilution, take the above-mentioned dilution bacteria suspensions of 1mL in flat board, use fine jade
Fat pour plate, is mixed, it is to be solidified after be inverted in 37 DEG C of incubated 24h, calculate total plate count, the computational methods of total plate count
With reference to GB 47892-2010, fungistatic effect is shown in Table 2.
Bacteriostasis rate (%)=(blank control total plate count-gel total plate count)/blank control total plate count * 100
The bacteriostatic test result of table 2
As seen from Table 2, the embodiment of the present invention 1~7 repair gel to the bacteriostasis rate of the normal infectious bacteria of the surface of a wound 90% with
On, each group is optimal to the fungistatic effect of Escherichia coli and staphylococcus aureus;Above-mentioned 8 groups of fungistatic effect sorts from high to low
For:The > comparative examples 1 of 7 > embodiments of embodiment 4 > embodiments, 6 > embodiments, 5 > embodiments, 2 > embodiments, 3 > embodiments 1, it is real
4 groups of bacteriostasis rate highests to bacteria to be tested of example are applied, its fungistatic effect is best.Comparative example 1 is fine due to changing modified Nano crystallite
The proportioning of dimension element and sodium carboxymethylcellulose, the fungistatic effect that its gained repairs gel has compared with embodiment 4 significantly will be low, and contrast
The fungistatic effect of embodiment 2 and embodiment 4 can be seen that, when modified Nano microcrystalline cellulose is pressed with sodium carboxymethylcellulose in formula
1:The fungistatic effect of gel can be significantly improved when 0.5 weight is than compounding, this is probably because the proportioning can farthest increase
The contact area of big gel and the surface of a wound, so as to improve the fungistatic effect of gel;Comparative example 1 and embodiment 2 understand that modification is received
Rice microcrystalline cellulose and sodium carboxymethylcellulose compounding and modified Nano microcrystalline cellulose, sodium carboxymethylcellulose and ethoxy are fine
The plain three's compounding of dimension is compared, and the former can more improve the fungistatic effect of gel;Comparative example 2 is understood with embodiment 3, is used alone
Algaroba glue is compared with by konjac glucomannan, algaroba glue compounding use, and the gelling performance formed is more preferable;Comparative example 4 and reality
Apply example 7 to understand, polyethylene glycol is used alone as penetrating agent compared with by polyethylene glycol and polyglycereol compounding use, the former can carry
The bacteriostasis of high gel, polyethylene glycol, which is used alone, as penetrating agent in this explanation can make nutritional ingredient inside gel more
It hurry up, more effectively ooze out, play a role.
Summary experiment can show that the embodiment of the present invention 4 repairs gel prominent in terms of stability and fungistatic effect
The performance gone out, therefore embodiment 4 is preferred embodiment.
Different carboxymethyl chitosans, cellulose derivative water-soluble polymer and carbomer are with comparison wound repair gel
The influence of performance
This test example is control group with embodiment 4, there is provided 9 kinds of different carboxymethyl chitosans, cellulose derivatives are water-soluble
Property polymer and carbomer proportioning reparation gel, be respectively labeled as 1. -9. group, investigate its stability to plural gel,
The influence of sense organ and bacteriostasis property, with such as table 3.
The different carboxymethyl chitosans of table 3, cellulose derivative water-soluble polymer and carbomer proportioning
Note:Stability test, antibacterial test reference stability test and bacteriostatic test method of testing.
Stability, organoleptic properties and bacteriostasis property according to the reparation gel obtained by said ratio is detected, it is right
As a result it is analyzed as follows:
Organoleptic properties analysis shows, each proportioning gained all transparent semi-solid of gel outward appearance, homogeneous exquisiteness has light
Pool, is coated with refrigerant sense;The denseness of gel is reduced afterwards as the rise of carbomer addition first increases, and is added with carboxymethyl chitosan
The increase of dosage and decrease, the change of cellulose derivative water-soluble polymer addition on the denseness influence of gel not
Greatly, and denseness height is unfavorable for painting exhibition, compare each group, finally show that 1% carboxymethyl chitosan, 1% cellulose derivative are water-soluble
Polymer and 1.5% carbomer compounding gained repair gel and have more preferable sensory effects;
Stability analysis shows that each proportioning gained gel is after hermetically storing 18 months, no layering and syneresis phenomenon,
But mildew situation is shown, as the addition of carboxymethyl chitosan, carbomer and cellulose derivative water-soluble polymer is higher,
Gel is less susceptible to mildew, and storage-stable is better.
Bacteriostasis property analysis shows, the fungistatic effect of gel is with cellulose derivative water-soluble polymer and carboxymethyl shell
The increase of glycan addition and improve, the addition of carbomer influences little to the fungistatic effect of gel.
Therefore, comprehensive three indexs, draw with 1% cellulose derivative water-soluble polymer, 1.5% cellulose derivative
Water-soluble polymer and 1.5% carbomer compounding gained, which repair gel, has more excellent bacteriostasis property, organoleptic properties and steady
It is qualitative.
Clinical test
1st, data and method
1.1 general information:Jingzhou City of Hubei Province in May, 2009 is in May, 2012 burned patient 150, man 80, female
70,7~70 years old age, average age 35 ± 2 years old;It is divided into according to burn and scald reason:Boiling water burn 68, fire wound 82;
It is divided into according to burn and scald degree:Deep II degree of burn and scald 90, III degree of burn and scald 60.
1.2 packets and medication
Packet:Above-mentioned II degree of depth burn and scald 90 patient is randomly divided into 5 groups, every group of 18 people, each group medication is as follows:
4 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 4 on the skin;
5 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 5 on the skin;
6 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 6 on the skin;
7 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 7 on the skin;
1 group of comparative example:Put reparation gel prepared by comparative example 1 of the present invention on the skin outside;
Above-mentioned III degree of burn and scald, 60 patients are divided into 5 groups, every group of 12 people, each group medication is as follows:
4 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 4 on the skin;
5 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 5 on the skin;
6 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 6 on the skin;
7 groups of embodiment:The outer reparation gel for putting the preparation of the embodiment of the present invention 7 on the skin;
1 group of comparative example:Put reparation gel prepared by comparative example 1 of the present invention on the skin outside;
Medication:Under sterile working, by the surface of a wound routine disinfection of boiling hot burn, first with the Iodophor and physiology salt of low concentration
Water simply cleans the surface of a wound, removes attachment and the elephant skin that come off, the high blister tap of tension force, residual epithelium is kept as far as possible, is cut
Except coming off or downright bad epidermis, the thorough debridement of infective wound surface row applies to outside the surface of a wound or sprays corresponding decoction, every 3~4 hours of daytime
1 time, daily coating 3~4 times.After medication fully exposure the surface of a wound, can not cover, prevent that, into water, winter notes warming, each group according to
Burn and scald area determines dosage, by can whole flap coverages be defined.
1.3 recovery from illness criterions of therapeutical effect:Swelling disappears after medication, and pain disappears, and the surface of a wound has epidermis without infection, subcrustal healing
Growth, the surface of a wound is repaired or all repaired substantially.Recovery from illness number in 7d, 14d, 21d is recorded after medication, 14d cure rates, 14d is calculated
Recovery from illness number/case total number of persons × 100% in cure rate=14d;When time needed for defining the complete epithelialization of the surface of a wound is healing
Between, the healing time of each patient is recorded, and t inspections are carried out to healing time and is compared;Record the surface of a wound scar of burned patient
Situation, records patient's number of cases of scar, calculates scar rate, patient's number of cases/case total number of persons of scar rate=scar
× 100%;Applied statistics software is analyzed, with p<0.05 has significant difference, and result of the test is shown in Table 4.
1.4 result of the test.
The result of the test of table 4
As shown in Table 4, in deep II degree for the treatment of and III degree of burn and scald, the embodiment of the present invention 1~3 is repaired gel and achieved
Excellent effect, particularly has significant progress in terms of improving 14d cure rates and shortening healing time;From present invention implementation
Example 1~3 is repaired from the point of view of the scar rate of gel for treating burn and scald, with the exacerbation of burn and scald degree, deep II degree of present invention treatment with
III degree of burn and scald scar rate is extremely low, it is clear that the present invention repairs gel staying after treatment burn and scald and expectation is achieved in scar problem
Less than technique effect;And summary indices, it is found that the therapeutic effect of the embodiment of the present invention 4 is optimal.
Claims (6)
1. a kind of reparation gel containing growth factor, it is characterised in that be made up of the component of following mass percent:
0.001~0.02% growth factor, the growth factor be selected from recombinant human epidermal growth factor and/or recombination human basic into
Fibroblast growth factor;
0.05~1% alkaline polysaccharide, the alkaline polysaccharide is selected from carboxymethyl chitosan, and the molecular weight of the carboxymethyl chitosan is
2~4 × 103, substitution value is 80~90%;
0.5~2% cellulose derivative water-soluble polymer, the cellulose derivative water-soluble polymer is micro- by modified Nano
Crystalline cellulose and sodium carboxymethylcellulose press 1:0.2~0.5 weight is than composition;
0.05~2% natural plant polyose, the natural plant polyose is selected from algaroba glue;
The natural water-soluble copolymer of 0.01~1% exocellular polysaccharide class, the natural water-soluble copolymer of the exocellular polysaccharide class by
Xanthans and gellan gum press 1:1~3 weight is than composition;
0.1~2% carbomer;
12~40% NMFs, the NMF is selected from polyalcohols;
0.05~6%pH conditioning agents, one or more of the pH adjusting agent in triethanolamine, citric acid and tartaric acid;
0.6~6% cutaneous permeable agent, the cutaneous permeable agent is selected from Tween 80 and/or azone;
0.1~0.3% penetrating agent, one or more of the penetrating agent in polyethylene glycol, polypropylene glycol and polyglycereol;
0.01~2% hyaluronic acid;
40~70% deionized waters.
2. the reparation gel as claimed in claim 1 containing growth factor, it is characterised in that the growth factor is by recombined human table
Skin growth factor and recombination human basic fibroblast growth factor press 1:0.5~1 weight is than composition.
3. the reparation gel as claimed in claim 1 containing growth factor, it is characterised in that the NMF is selected from glycerine.
4. the reparation gel as claimed in claim 1 containing growth factor, it is characterised in that the pH adjusting agent is selected from three ethanol
Amine.
5. the reparation gel as claimed in claim 1 containing growth factor, it is characterised in that the penetrating agent is selected from poly- second two
Alcohol.
6. a kind of preparation method of the reparation gel containing growth factor, it is characterised in that comprise the following steps:
A) take 0.05~1% alkaline polysaccharide to be added in deionized water, be mixed evenly, obtain 0.5~1wt% alkaline polysaccharide
Solution, takes 0.5~2% cellulose derivative water-soluble polymer to be added in deionized water, is mixed evenly, obtain 0.1~
1wt% cellulose derivative water-soluble polymer solution;Above two solution is well mixed, is swelled, obtain alkaline polysaccharide/
Cellulose derivative water-soluble polymer support;
B) take 0.1~2% carbomer, be added to while stirring in deionized water, be swelled 12~24h, add above-mentioned alkaline polysaccharide/
Cellulose derivative water-soluble polymer support, stirs 10~15min, continuously adds 0.05~2% natural plant polyose, 0.01
Natural water-soluble copolymer, 12~40% NMFs, 0.6~6% cutaneous permeable agent, the 0.01-2% of~1% exocellular polysaccharide class
Hyaluronic acid and 0.1~0.3% penetrating agent, stir 20~35min, and it is 6.0~7.0 to add pH adjusting agent regulation pH, must be answered
Close gel;
C) take 0.001~0.02% growth factor to be dissolved in deionized water and be configured to growth factor solution, by growth factor solution plus
Enter to above-mentioned steps B) gained plural gel in, be well mixed, be stored at room temperature 2~5h, produce.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610375170.7A CN105816911B (en) | 2016-05-31 | 2016-05-31 | A kind of reparation gel containing growth factor and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610375170.7A CN105816911B (en) | 2016-05-31 | 2016-05-31 | A kind of reparation gel containing growth factor and preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105816911A CN105816911A (en) | 2016-08-03 |
CN105816911B true CN105816911B (en) | 2017-07-28 |
Family
ID=56531605
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610375170.7A Active CN105816911B (en) | 2016-05-31 | 2016-05-31 | A kind of reparation gel containing growth factor and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105816911B (en) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107185031B (en) * | 2017-05-23 | 2019-03-26 | 广州润虹医药科技股份有限公司 | A kind of biologically active medical dressing and preparation method thereof |
CN109568644A (en) * | 2017-09-29 | 2019-04-05 | 温州医科大学 | A kind of composite growth factor antibacterial promotees to repair gel and the preparation method and application thereof |
CN109568645B (en) * | 2017-09-29 | 2021-11-02 | 温州医科大学 | A kind of composite growth factor-promoting repair gel and preparation method and application thereof |
CN108210887A (en) * | 2017-11-27 | 2018-06-29 | 南京天纵易康生物科技股份有限公司 | A kind of Medical cold application and preparation method thereof |
CN108434512A (en) * | 2018-03-30 | 2018-08-24 | 东莞御治医疗器械有限公司 | Medical cold compress gel for postoperative treatment and preparation method thereof |
CN108635622A (en) * | 2018-05-15 | 2018-10-12 | 杭州易敏生物医药科技有限公司 | New liquid gauze and its preparation method and application |
CN110623870A (en) * | 2018-06-21 | 2019-12-31 | 刘方圆 | Moisturizing gel mask and preparation method thereof |
CN109078171A (en) * | 2018-09-10 | 2018-12-25 | 因之彩生物科技(武汉)有限公司 | A kind of topical composition and its application and remedy for external use |
CN111777707B (en) * | 2020-07-02 | 2022-12-16 | 南京紫鸿生物科技有限公司 | High-concentration alcohol gel and carbomer for high-concentration alcohol gel |
CN111973801B (en) * | 2020-08-18 | 2022-01-14 | 稳健医疗用品股份有限公司 | Hydrogel for anti-inflammatory repair and preparation method thereof |
CN112089883B (en) * | 2020-09-14 | 2022-01-04 | 海南希睿达生物技术有限公司 | Medical cold compress dressing and preparation method thereof |
CN112957519A (en) * | 2021-01-27 | 2021-06-15 | 徐州辉朗医疗科技有限公司 | Composition for preparing hydrogel for promoting wound healing, hydrogel and preparation method thereof |
CN113069533A (en) * | 2021-03-08 | 2021-07-06 | 温州医科大学 | Long-acting fibroblast growth factor gel |
CN115177782B (en) * | 2021-04-02 | 2023-07-18 | 诺一迈尔(山东)医学科技有限公司 | Liquid band-aid with high air permeability and healing promotion function and preparation method thereof |
CN114129710B (en) * | 2021-12-09 | 2024-04-26 | 温州医科大学附属第二医院(温州医科大学附属育英儿童医院) | Fibroblast growth factor hydrogel and preparation method thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102949709A (en) * | 2011-08-18 | 2013-03-06 | 中国科学院大连化学物理研究所 | External gel used for treating diabetic foot, and preparation method and application thereof |
CN103083713A (en) * | 2012-12-10 | 2013-05-08 | 江苏华亿细胞组织工程有限公司 | Sterile polymerized covering dressing for wound surface |
-
2016
- 2016-05-31 CN CN201610375170.7A patent/CN105816911B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102949709A (en) * | 2011-08-18 | 2013-03-06 | 中国科学院大连化学物理研究所 | External gel used for treating diabetic foot, and preparation method and application thereof |
CN103083713A (en) * | 2012-12-10 | 2013-05-08 | 江苏华亿细胞组织工程有限公司 | Sterile polymerized covering dressing for wound surface |
Also Published As
Publication number | Publication date |
---|---|
CN105816911A (en) | 2016-08-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105816911B (en) | A kind of reparation gel containing growth factor and preparation method thereof | |
CN103083713B (en) | A kind of aseptic polymerization wound-surface cover dressing | |
DE69032125T2 (en) | GEL Wound Dressing Compositions And Method For Using Them | |
DE69914928T2 (en) | POLYMER COMPLEXES OF GLUCURONOGLUCANS | |
CN106822988B (en) | Alginate fiber functional dressing and application thereof, and alginate fiber functional dressing patch | |
JP6069394B2 (en) | Pharmaceutical composition | |
US20100316739A1 (en) | Chitosan gel for dermatological use, production method therefor and use of same | |
CN104257639B (en) | A kind of liniment for Wound treating and preparation method thereof | |
BRPI0717734B1 (en) | METHOD FOR PREPARING A DRY POWDER FROM POLYMERIC NANOParticles, DRY POWDER AND USE | |
RU2422133C1 (en) | Hydrophylic gel, method of its obtaining (versions), wound covering and based on it bandage means | |
CN108066814A (en) | A kind of preparation method of bacteria cellulose antiseptic dressing | |
CN104258456B (en) | A kind of wound repair gel containing hexagonal mesoporous silicon and preparation method thereof | |
CN114984301A (en) | Antibacterial dressing for promoting wound surface to heal without scars and preparation method thereof | |
CN104623718A (en) | Chitosan petrolatum gauze and preparation method thereof | |
Parwani et al. | Gum acacia-PVA hydrogel blends for wound healing | |
CN106421868A (en) | Chitosan quaternary ammonium salt porcine acellular dermal matrix dressing material and preparation method thereof | |
Barman et al. | Cellulose-based hydrogels for pharmaceutical and biomedical applications | |
CN104740141B (en) | A kind of antimicrobial spray and preparation method thereof | |
CN104069535B (en) | A kind of Preparation method and use of biological activity composite membrane bleeding-stopping dressing | |
CN111973801B (en) | Hydrogel for anti-inflammatory repair and preparation method thereof | |
US11058712B2 (en) | Film for topical application in the treatment of skin lesions and method of obtaining and applying same | |
CN106581699A (en) | Bactericidal aseptic solid medical ultrasonic coupling patch and preparation method thereof | |
Rani et al. | An overview on hydrophilic three dimensional networks: Hydrogels | |
CN112023110B (en) | Active antibacterial dressing based on bamboo fungus egg extract | |
RU2649790C1 (en) | Antiseptic composition containing unithiol and dimethylsulfoxide, application of such a composition and method of wound treatment with the use of it |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CP03 | Change of name, title or address |
Address after: 442000 No. 698 Bingbing Road, Yunyang Economic Development Zone, Shiyan City, Hubei Province Patentee after: Hubei Bingbing Pharmaceutical Industry (Group) Co., Ltd. Address before: Longyang Road 430056 Hubei city of Wuhan province Kangda street Hanyang District No. 5 Patentee before: Bingbing Pharmaceutical Co., Ltd., Wuhan |
|
CP03 | Change of name, title or address |