CN116036247B - Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof - Google Patents
Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof Download PDFInfo
- Publication number
- CN116036247B CN116036247B CN202310064800.9A CN202310064800A CN116036247B CN 116036247 B CN116036247 B CN 116036247B CN 202310064800 A CN202310064800 A CN 202310064800A CN 116036247 B CN116036247 B CN 116036247B
- Authority
- CN
- China
- Prior art keywords
- wound healing
- parts
- promoting
- wound
- beta
- 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
- 230000029663 wound healing Effects 0.000 title claims abstract description 70
- 230000001737 promoting effect Effects 0.000 title claims abstract description 33
- 230000033115 angiogenesis Effects 0.000 title claims abstract description 27
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims abstract description 18
- 230000028709 inflammatory response Effects 0.000 title claims description 6
- 108010038807 Oligopeptides Proteins 0.000 claims abstract description 38
- 102000015636 Oligopeptides Human genes 0.000 claims abstract description 38
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 25
- 229920001184 polypeptide Polymers 0.000 claims abstract description 22
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 22
- 102000004506 Blood Proteins Human genes 0.000 claims abstract description 20
- 108010017384 Blood Proteins Proteins 0.000 claims abstract description 20
- 102000008186 Collagen Human genes 0.000 claims abstract description 20
- 108010035532 Collagen Proteins 0.000 claims abstract description 20
- 229920001436 collagen Polymers 0.000 claims abstract description 20
- 241000251468 Actinopterygii Species 0.000 claims abstract description 19
- 241000209140 Triticum Species 0.000 claims abstract description 19
- 235000021307 Triticum Nutrition 0.000 claims abstract description 19
- 229940119217 chamomile extract Drugs 0.000 claims abstract description 18
- 235000020221 chamomile extract Nutrition 0.000 claims abstract description 18
- 230000000694 effects Effects 0.000 claims abstract description 17
- 239000000843 powder Substances 0.000 claims description 20
- 235000017784 Mespilus germanica Nutrition 0.000 claims description 16
- 244000182216 Mimusops elengi Species 0.000 claims description 16
- 235000000560 Mimusops elengi Nutrition 0.000 claims description 16
- 235000007837 Vangueria infausta Nutrition 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 12
- 235000013325 dietary fiber Nutrition 0.000 claims description 11
- 108010001441 Phosphopeptides Proteins 0.000 claims description 9
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 9
- 239000005018 casein Substances 0.000 claims description 9
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 claims description 9
- 235000021240 caseins Nutrition 0.000 claims description 9
- 229960000306 zinc gluconate Drugs 0.000 claims description 9
- 235000011478 zinc gluconate Nutrition 0.000 claims description 9
- 239000011670 zinc gluconate Substances 0.000 claims description 9
- 230000002757 inflammatory effect Effects 0.000 claims description 7
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 229930195729 fatty acid Natural products 0.000 claims description 6
- 239000000194 fatty acid Substances 0.000 claims description 6
- 150000004665 fatty acids Chemical class 0.000 claims description 6
- WLJUMPWVUPNXMF-UHFFFAOYSA-L calcium;3-hydroxy-3-methylbutanoate Chemical compound [Ca+2].CC(C)(O)CC([O-])=O.CC(C)(O)CC([O-])=O WLJUMPWVUPNXMF-UHFFFAOYSA-L 0.000 claims description 5
- 210000002966 serum Anatomy 0.000 claims description 5
- 238000007634 remodeling Methods 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 230000021164 cell adhesion Effects 0.000 claims description 2
- 230000012292 cell migration Effects 0.000 claims description 2
- 230000004663 cell proliferation Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000013508 migration Methods 0.000 claims description 2
- 230000037314 wound repair Effects 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 abstract description 15
- 230000004054 inflammatory process Effects 0.000 abstract description 15
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- JGFBQFKZKSSODQ-UHFFFAOYSA-N Isothiocyanatocyclopropane Chemical compound S=C=NC1CC1 JGFBQFKZKSSODQ-UHFFFAOYSA-N 0.000 abstract 1
- PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 abstract 1
- 229910052791 calcium Inorganic materials 0.000 abstract 1
- 239000011575 calcium Substances 0.000 abstract 1
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 abstract 1
- 208000027418 Wounds and injury Diseases 0.000 description 40
- 206010052428 Wound Diseases 0.000 description 39
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- 239000000463 material Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000000465 moulding Methods 0.000 description 10
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 9
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 9
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 9
- 230000035876 healing Effects 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- PVXPPJIGRGXGCY-TZLCEDOOSA-N 6-O-alpha-D-glucopyranosyl-D-fructofuranose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)C(O)(CO)O1 PVXPPJIGRGXGCY-TZLCEDOOSA-N 0.000 description 8
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 description 8
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 description 8
- 239000004376 Sucralose Substances 0.000 description 8
- YZHOZVWZUXBPMD-UHFFFAOYSA-N calcium;3-hydroxy-3-methylbutanoic acid Chemical compound [Ca].CC(C)(O)CC(O)=O YZHOZVWZUXBPMD-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 8
- 235000019408 sucralose Nutrition 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 206010063560 Excessive granulation tissue Diseases 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 210000001126 granulation tissue Anatomy 0.000 description 7
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 238000010166 immunofluorescence Methods 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 229920003081 Povidone K 30 Polymers 0.000 description 4
- 239000000853 adhesive Substances 0.000 description 4
- 230000001070 adhesive effect Effects 0.000 description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 4
- 229910052782 aluminium Inorganic materials 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000000889 atomisation Methods 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000011049 filling Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010039509 Scab Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229960002146 guaifenesin Drugs 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- FYSSBMZUBSBFJL-UHFFFAOYSA-N 3-hydroxydecanoic acid Chemical compound CCCCCCCC(O)CC(O)=O FYSSBMZUBSBFJL-UHFFFAOYSA-N 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- AZJQQNWSSLCLJN-UHFFFAOYSA-N 2-ethoxyquinoline Chemical compound C1=CC=CC2=NC(OCC)=CC=C21 AZJQQNWSSLCLJN-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria 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
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101710116034 Immunity protein Proteins 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000006427 angiogenic response Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 231100000749 chronicity Toxicity 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000001804 debridement Methods 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000009762 endothelial cell differentiation Effects 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 150000002190 fatty acyls Chemical group 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002313 glycerolipids Chemical class 0.000 description 1
- 150000002327 glycerophospholipids Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000009442 healing mechanism Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000009854 mucosal lesion Effects 0.000 description 1
- 230000031990 negative regulation of inflammatory response Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035752 proliferative phase Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940126673 western medicines Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/315—Zinc compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
- A61K36/815—Lycium (desert-thorn)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/41—Porphyrin- or corrin-ring-containing peptides
- A61K38/42—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Botany (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Alternative & Traditional Medicine (AREA)
- Dermatology (AREA)
- Marine Sciences & Fisheries (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Biomedical Technology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing and application thereof, wherein the composition comprises the following components in parts by weight: 0.1-100 parts of wheat oligopeptide, 0.1-100 parts of marine fish skin collagen oligopeptide and 0.1-100 parts of blood protein polypeptide. The composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing provided by the invention is prepared by taking marine fish skin collagen oligopeptide, wheat oligopeptide and blood protein polypeptide as main components and matching chamomile extract and beta-hydroxy-beta-calcium methylbutyrate, and achieves the effects of promoting wound healing and a plurality of links of wound healing by inhibiting inflammatory reaction and promoting angiogenesis reaction, thereby providing important practical significance for developing products for promoting wound healing.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof.
Background
The skin is the largest organ of human body, and has the key functions of protecting viscera from pathogen invasion, regulating body temperature and the like. Skin wounds caused by burns, trauma and chronicity negatively affect the quality of life and health of the patient and create significant economic and social burden. Wound healing is a complex dynamic process that can be divided into four phases: coagulation phase, inflammatory phase, proliferation phase and remodeling phase, which overlap in time and space. However, there is still a lack of complete understanding of the wound healing process and mechanism; how to promote wound healing in particular remains a significant clinical challenge. Inflammatory phases generally occur in early wound healing, especially the first three days after debridement, and usually manifest as slight redness, swelling, compression pain, etc. in the wound area. If the wound is polluted seriously, especially the bacteria with stronger pathogenicity, the wound infection is easy to cause, the pus accumulation phenomenon occurs in the wound, and the period of wound healing is greatly prolonged. As a key link of wound healing, angiogenesis provides oxygen, growth factors and immune support for healed tissues, and promoting massive generation of blood vessels in the wound healing stage can enable the tissues to obtain more oxygen and nutrition, so that the healing efficiency and quality are improved, and conversely, the healing rate is reduced by reducing angiogenesis.
The drug treatment is the most main mode of wound treatment, more traditional Chinese medicines and western medicines are used for treating wound healing in combination at present, and the clinical effect is remarkable. Currently, as a result of the clinical emergence of resistance to a variety of antibiotics, it is urgent to find new drugs that promote wound healing. The polypeptide products are small in molecule, high in action selectivity, easy to obtain and free of obvious side effects, so that the polypeptide products currently become the primary choice for treating wound healing.
The existing peptide products for promoting wound healing mainly take collagen peptide as a main raw material, and supplement protein in the wound healing process, so that sufficient protein is provided for wound healing, but the related peptide products are not designed for inflammatory reaction and angiogenesis promotion in the wound healing engineering at present in the blood stage, inflammatory stage, proliferation stage and remodelling stage of wound healing, and the wound healing needs to take a plurality of links into consideration to achieve ideal effects.
Disclosure of Invention
In view of the above, an object of the present invention is to provide a composition and application for inhibiting inflammatory reaction, promoting angiogenesis and wound healing, which can simultaneously promote inflammatory reaction and angiogenesis in the wound healing process.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a composition for inhibiting inflammatory response, promoting angiogenesis and wound healing, comprising the following components in parts by weight:
0.1-100 parts of wheat oligopeptide, 0.1-100 parts of marine fish skin collagen oligopeptide and 0.1-100 parts of blood protein polypeptide.
Optionally, the composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing further comprises the following components in parts by weight:
0.01-2 parts of chamomile extract, 0.1-20 parts of beta-hydroxy beta-methyl calcium butyrate and 0.01-3 parts of medlar powder.
The invention can be prepared into conventional oral preparations including but not limited to granules, oral liquid and the like by adopting pharmaceutically acceptable preparation processes and auxiliary materials.
The product has the characteristics of low cost, good curative effect, no toxic or side effect due to natural sources.
Optionally, the composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing further comprises the following components in parts by weight:
0.001-1 part of zinc gluconate, 0.01-5 parts of casein phosphopeptide and 1-100 parts of water-soluble dietary fiber.
Optionally, the composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing comprises the following components in parts by weight:
0.1-60 parts of wheat oligopeptide, 0.1-60 parts of marine fish skin collagen oligopeptide, 0.1-60 parts of blood protein polypeptide, 0.1-1.5 parts of chamomile extract, 0.5-10 parts of beta-hydroxy-beta-methylbutyrate calcium and 0.1-2 parts of medlar powder.
Optionally, the composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing comprises the following components in parts by weight:
1.8 parts of wheat oligopeptide, 1.8 parts of marine fish skin collagen oligopeptide, 0.4 part of blood protein polypeptide, 0.1 part of chamomile extract, 1 part of beta-hydroxy-beta-methylbutyrate calcium, 0.2 part of medlar powder and adding water to supplement 100 parts.
The invention also provides application of the composition in preparing medicines for inhibiting inflammatory reaction and promoting angiogenesis and wound healing.
The composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing and the application thereof provided by the invention are obtained by taking marine fish skin collagen oligopeptide, wheat oligopeptide and blood protein polypeptide as main components and matching chamomile extract and beta-hydroxy-beta-methyl calcium butyrate, and the effects of promoting wound healing are achieved by inhibiting inflammatory reaction and promoting angiogenesis reaction, a plurality of links of wound healing are considered, and important theoretical and practical significance is provided for developing products for promoting wound healing.
In the composition, chamomile extract has the effects of resisting inflammation and relieving pain, beta-hydroxy-beta-methylbutyric acid calcium has the effects of accelerating protein synthesis or preventing proteolysis, medlar powder can enhance immunity, and blood protein polypeptide has the effect of enriching blood. The invention can be prepared by adopting pharmaceutically acceptable preparation process and auxiliary materials, including but not limited to conventional oral preparations such as granules, oral liquid and the like, and has the characteristics of low cost, good curative effect, no toxic or side effect due to natural sources and the like.
Drawings
FIG. 1 is a model set, example 5 and implementation 7 of the wound surface shape variation;
FIG. 2 is hematoxylin and eosin staining of wound tissue in model group, example 5 and example 7;
FIG. 3 shows the distribution of VEGF in the granulation tissue at the wound site in the model group, example 5 and example 7;
FIG. 4 shows the immunofluorescence intensity of CD34 in model set, example 5 and example 7;
FIG. 5 shows the CTGF immunofluorescence intensities of the model set, example 5 and example 7;
FIG. 6 is a graph comparing D-mannitol and fatty acid content in serum for model group, example 5 and example 7.
Detailed Description
The invention will be described more fully hereinafter with reference to the accompanying examples in order to facilitate an understanding of the invention, however, the invention may be embodied in many different forms and is not limited to the examples described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
The following examples are provided to further illustrate embodiments of the invention. The embodiments of the present invention are not limited to the following specific embodiments. The modification can be appropriately performed within the scope of the main claim.
Example 1
200g of wheat oligopeptide, 200g of marine fish skin collagen oligopeptide, 50g of blood protein polypeptide, 15g of chamomile extract, 100g of beta-hydroxy-beta-methylbutyric acid calcium, 20g of medlar powder, 200g of water-soluble dietary fiber, 6g of casein phosphopeptide, 2g of zinc gluconate and 285g of sugar powder are taken, all materials are uniformly mixed and then are respectively sieved by a 100-mesh sieve, the uniformly mixed materials are boiled and granulated by using a 10% aqueous solution of povidone K30 as an adhesive, the atomization pressure is controlled to be 0.2Mpa, the material temperature is 42 ℃, the air inlet temperature is 70 ℃, the obtained particles are packaged by aluminum paper, and each bag is packaged by 20-mesh sieve.
Example 2
400g of wheat oligopeptide, 300g of marine fish skin collagen oligopeptide, 100g of blood protein polypeptide, 20g of chamomile extract, 200g of beta-hydroxy-beta-methyl calcium butyrate, 30g of medlar powder and 320g of sugar powder are taken, all materials are uniformly mixed and are respectively sieved by a 100-mesh sieve, the uniformly mixed materials are boiled and granulated by using a 10% aqueous solution of povidone K30 as an adhesive, the atomization pressure is controlled to be 0.2Mpa, the material temperature is 42 ℃, the air inlet temperature is 70 ℃, the obtained granules are granulated by using a 20-mesh sieve, and are packaged by aluminum paper, and each bag is 5g.
Example 3
Taking 300g of wheat oligopeptide, 400g of marine fish skin collagen oligopeptide, 100g of blood protein polypeptide, 20g of chamomile extract, 200g of beta-hydroxy-beta-methyl calcium butyrate, 30g of medlar powder and 320g of sugar powder, uniformly mixing all materials, sieving the materials with a 100-mesh sieve respectively, boiling and granulating the uniformly mixed materials by using a 10% aqueous solution of povidone K30 as an adhesive, controlling the atomization pressure to be 0.2Mpa, controlling the material temperature to be 42 ℃, controlling the air inlet temperature to be 70 ℃, finishing the obtained particles by using a 20-mesh sieve, packaging the particles by using aluminum paper, and packaging each bag by 5g.
Example 4
200g of wheat oligopeptide, 200g of marine fish skin collagen oligopeptide, 100g of blood protein polypeptide and 100g of sugar powder are taken, all materials are mixed uniformly and then respectively pass through a 100-mesh sieve, the uniformly mixed materials are boiled and granulated by using 10% aqueous solution of povidone K30 as an adhesive, the atomization pressure is controlled to be 0.2Mpa, the material temperature is 42 ℃, the air inlet temperature is 70 ℃, the obtained granules are granulated by using a 20-mesh sieve, and the granules are packaged by aluminum paper, wherein each bag is 6g.
Example 5
18g of wheat oligopeptide, 18g of marine fish skin collagen oligopeptide, 4g of blood protein polypeptide, 1g of chamomile extract, 10g of beta-hydroxy-beta-methylbutyric acid calcium, 2g of medlar powder, 10g of water-soluble dietary fiber, 0.4g of casein phosphopeptide, 0.06g of zinc gluconate, 0.15g of sucralose, 2.2g of citric acid and 8g of isomaltulose are taken, 500ml of purified water is added into a batching tank, and the wheat oligopeptide, the marine fish skin collagen oligopeptide, the blood protein polypeptide, the chamomile extract, the beta-hydroxy-beta-methylbutyric acid calcium, the medlar powder, the water-soluble dietary fiber and the isomaltulose are sequentially added and stirred for dissolution. Filtering with plate-frame filter to obtain filtrate. After dissolving sucralose, casein phosphopeptide, zinc gluconate and citric acid with a proper amount of purified water, adding water to 1000ml, stirring for 15 minutes, adding essence, stirring for 10 minutes, and filtering with a 0.45 μm filter element. Filling, sterilizing at 105deg.C for 30 min per bottle 100 ml.
Example 6
16g of wheat oligopeptide, 16g of marine fish skin collagen oligopeptide, 8g of blood protein polypeptide, 0.5g of chamomile extract, 20g of beta-hydroxy-beta-methylbutyric acid calcium, 2g of medlar powder, 10g of water-soluble dietary fiber, 0.4g of casein phosphopeptide, 0.06g of zinc gluconate, 0.15g of sucralose, 2.2g of citric acid and 8g of isomaltulose are taken, 500ml of purified water is added into a batching tank, and the wheat oligopeptide, the marine fish skin collagen oligopeptide, the blood protein polypeptide, the chamomile extract, the beta-hydroxy-beta-methylbutyric acid calcium, the medlar powder, the water-soluble dietary fiber and the isomaltulose are sequentially added and stirred for dissolution. Filtering with plate-frame filter to obtain filtrate. After dissolving sucralose, casein phosphopeptide, zinc gluconate and citric acid with a proper amount of purified water, adding water to 1000ml, stirring for 15 minutes, adding essence, stirring for 10 minutes, and filtering with a 0.45 μm filter element. Filling, sterilizing at 105deg.C for 30 min per bottle 100 ml.
Example 7
Taking 20g of wheat oligopeptide, 12g of marine fish skin collagen oligopeptide, 8g of blood protein polypeptide, 1g of chamomile extract, 20g of beta-hydroxy-beta-methylbutyric acid calcium, 2g of medlar powder, 10g of water-soluble dietary fiber, 0.4g of casein phosphopeptide, 0.06g of zinc gluconate, 0.15g of sucralose and 2.0g of citric acid, 8g of isomaltulose, adding 500ml of purified water into a batching tank, and sequentially adding the wheat oligopeptide, the marine fish skin collagen oligopeptide, the blood protein polypeptide, the chamomile extract, the beta-hydroxy-beta-methylbutyric acid calcium, the medlar powder, the water-soluble dietary fiber and the isomaltulose into the batching tank, and stirring to dissolve the materials. Filtering with plate-frame filter to obtain filtrate. After dissolving sucralose, casein phosphopeptide, zinc gluconate and citric acid with a proper amount of purified water, adding water to 1000ml, stirring for 15 minutes, adding essence, stirring for 10 minutes, and filtering with a 0.45 μm filter element. Filling, sterilizing at 105deg.C for 30 min per bottle 100 ml.
Example 8
12g of wheat oligopeptide, 20g of marine fish skin collagen oligopeptide, 8g of blood protein polypeptide, 2g of chamomile extract, 20g of beta-hydroxy-beta-methylbutyrate calcium, 2g of medlar powder, 10g of water-soluble dietary fiber, 0.15g of sucralose, 2.0g of citric acid and 8g of isomaltulose are taken, 500ml of purified water is added into a batching tank, and the wheat oligopeptide, the marine fish skin collagen oligopeptide, the blood protein polypeptide, the chamomile extract, the beta-hydroxy-beta-methylbutyrate calcium, the medlar powder, the water-soluble dietary fiber and the isomaltulose are sequentially added and stirred to be dissolved. Filtering with plate-frame filter to obtain filtrate. After dissolving sucralose and citric acid in a proper amount of purified water, adding the solution into the filtrate, adding water to 1000ml, stirring for 15 minutes, adding essence, stirring for 10 minutes, and filtering with a 0.45 μm filter element. Filling, sterilizing at 105deg.C for 30 min per bottle 100 ml.
In the present invention, the action mechanism of the compositions provided in example 5 and example 7 on wound healing was studied, and specifically includes the following methods:
1. inhibition of inflammatory response, promotion of angiogenesis and wound healing efficacy studies
1. Materials and methods
1.1 raw materials: examples 5 and 7 samples, positive control (yapekuai guaifenesin).
1.2 experimental animals: male Kunming mice, weighing 20-22g,6-8 weeks old, were supplied by Jiangsu Jiuyaokang biotechnology Co., ltd, and were licensed with the number SCXK (Su) 2018-0008.
1.3 experimental conditions: mice were kept in a clean environment in a river-Chinese medicine industry animal experiment center under the license number SYXK 2020-004. Laboratory temperature 24±2 ℃; relative humidity 45-65%; illumination period: 12 (day)/12 (night) hours.
1.4 experimental method:
1.4.1 rats were anesthetized with isoflurane, after which the back of the rats was shaved using a shaver to expose an area of about 3cm x 3cm to the back. Then the dehairing paste is used for dehairing, after 3 to 5 minutes, cotton is dipped with warm water to clean the back dehairing paste, and then the back moisture is wiped by dry cotton.
1.4.2 cleaning and disinfecting the rat back experimental area with iodophor, then pressing down on the rat back (basically ensuring the same position of each molding) with a skin sampler with the diameter of 10mm in a rotating way, forming a small notch, and removing the skin with an ophthalmic forceps and an ophthalmic scissors to form a circular wound with the diameter of 10 mm.
1.4.3 wound area measurement: rats were kept flat, photographed at the same height using an industrial high definition camera and subjected to primary wound measurement.
1.4.4 each group was followed daily by administration of the corresponding drug and wound area measurements were made on days 2, 3, 6, 10, 12, 14, respectively. The mice were anesthetized with isoflurane and photographed at the same height to make wound area measurements.
1.4.5 wound healing rate: wound area was photographed and measured with a camera every 2 days, and wound healing rate (wound healing rate, WHR) was calculated.
WHR=(D 0 -D n )/D 0 ×100%
Wherein: WHR is the wound healing rate WHR,%; d (D) 0 Diameter, cm, of the initial wound shape; d (D) n Is the diameter of the shape of the unhealed wound, cm.
1.4.6 sampling: after administration, 3d and 14d, the whole wound surface and normal skin tissues 5mm away from the wound edge are respectively sheared, and respectively placed in 4% paraformaldehyde for fixation and liquid nitrogen preservation.
1.4.7 pathology and immunohistochemistry: the new skin at the wound of the rat was excised, and the skin tissue was fixed in paraformaldehyde and embedded in paraffin. A 5 μm section of paraffin embedded skin was prepared for further experiments. H & E staining and Masson staining were used to examine mucosal lesions. For immunohistochemistry, the sections were incubated with anti-CD 34 protein and CTGF protein antibodies at 4 ℃. All results were observed by microscopy.
1.4.8 data analysis: data are expressed as mean.+ -. Standard deviation (mean.+ -. SEM), analyzed using One-way ANOVA, and then compared pairwise between groups using Dunnet method. The analysis results were statistically significant with P <0.05 and P <0.001 considered extremely significant differences. All data were analyzed using GraphPad Prism 8.0 statistical software package.
1.5 results
1.5.1 wound morphology Change observations
The healing of each group is shown in figure 1, and on day 2 after molding, animals of each group had crusted, no fluid exuded, and wound shrinkage was not evident, whereas on day 4 after molding, animals of the model group began crusting. On days 4, 6 and 10 after molding, the wound surface crusts of each group are continuously hardened, the surface around the wound is uneven, the skin shrinkage of the wound edge is obvious, wherein the skin shrinkage speed of the wound of each administration group is better than that of the model group. On day 12 after moulding, most of the mice in each group had fallen off the scab, and the healed sites began to grow hair, and each group was further scab. On day 14 after molding, each administration group presents flesh red new skin, the new flesh has complete tissue, and has better healing condition than the control group, and no hypertrophic scar and keloid generation.
1.5.2 healing Rate and scar reduction Rate
The wound surface area was photographed and measured with a camera every 2 days, and the measurement results were shown in table 1, according to the wound healing rate = (wound area on day 0 after molding-wound area on day of measurement)/(wound area on day 0 after molding) calculated result of 100%:
table 1: wound healing rate of mice
Note that: * Representing significance between Model and around, p <0.05, p < 0.01;
# represents significance between Model and Chuuun, # p <0.05, # p < 0.01;
significance between Model and improved Chuuun, p <0.05, p < 0.01.
As can be seen from Table 1, on day 3 of molding, the wound healing rates were close to 40% between each group, with no significant difference (P > 0.05) between the dosing group and the model group. On day 4 of modeling, the healing rate was significantly higher for each dosing group than for the model group. On day 6 of modeling, the healing rate was significantly higher for each dosing group than for the model group, with example 7 being better than for yapekuai and example 5. The healing rate was significantly higher for each of the dosing groups than for the model groups on days 8, 10 and 12 of modeling. On the 14 th day of molding, the wound healing rate of each group reaches more than 90%, the wound healing process is basically finished, and no significant difference (P is more than 0.05) exists between each group.
1.5.3H & E staining
As shown in fig. 2, several mice (n=6) were sacrificed per group on day 4 post-treatment and tissues were H & E stained. It can be seen that none of the wounds of each group healed completely, with the formation of granulation tissue starting in the full layer of dermal tissue and re-epithelialization of the wound border area. Wherein the model group granulation tissue was immature in development and strong inflammatory infiltration of lymphocytes, interstitial edema and hemorrhage were observed. Example 5, example 7 and yapekuai-guaifenesin, the whole layer of skin and subcutaneous tissue at the wound edge moves toward the center, and the wound gradually shrinks; although there was also a different degree of inflammatory cell infiltration, the granulation tissue was more mature than in the model group, indicating that each intervention group had some effect in promoting wound healing.
1.5.4VEGF grouping
VEGF (vascular endothelial growth factor) plays a vital role in the proliferative phase of wound healing, promoting endothelial cell migration, differentiation and tube formation, which are key factors in the early stages of angiogenesis. Studies have shown that new blood vessels appear at the earliest 3 days after injury. Thus, expression of VEGF in the granulation tissue area during wound healing represents the number of new blood vessels.
By detecting the distribution of VEGF in the granulation tissue of the wound part on the 4 th day after modeling through immunohistochemistry, as shown in figure 3, VEGF positive cells are brown, and the VEGF expression of the wound after the intervention of the yapekuai healin is not significantly different compared with that of a model group; whereas example 5 and example 7, in the dry prognosis, dispersed VEGF was observed in both infiltrating inflammatory cells and fibroblast-like cells in connective tissue at the wound site, and had a higher VEGF positive cell rate compared to model and yapeku-guaifenesin intervention groups. The results indicate that examples 5 and 7 are able to promote angiogenic responses during the wound healing process.
1.5.5CD34 immunofluorescence
Because wound healing requires angiogenesis, immunofluorescent staining of CD34 is used as a vascular system marker to study wound angiogenesis. As shown in FIG. 4, DAPI shows blue fluorescence and CD34 shows red fluorescence on each group of wound beds, indicating that there is a certain amount of neovascularization during wound healing, wherein the red fluorescence of example 5 and example 7 is greater than that of the model group, indicating that example 5 and example 7 both significantly increase the number of neovascularization, meaning that example 5 and example 7 promote angiogenesis and promote vascular network remodeling and wound healing. Furthermore, the yapekuai group did not show denser neovasculature at the wound site compared to the model group.
1.5.6CTGF immunofluorescence
Connective Tissue Growth Factor (CTGF) has a positive effect on the production of mature, well-organized and vascularized granulation tissue during the early wound healing phase. The distribution of CTGF in the wound on day 4 after molding was analyzed using immunofluorescence, DAPI blue fluorescence, CTGF red fluorescence, as shown in fig. 5, which is a representative image of the presence and distribution of CTGF positive cells in each group of wound healing regions, and the results indicate that example 5, example 7, and the quick healing group each showed more red fluorescence, i.e., more CTGF positive cells, than the model group. Wherein example 5 and example 7 fluoresce more red than the yapekine group, demonstrating that example 5 and example 7 interventions better promote cell adhesion, migration and proliferation than yapekine interventions at early stages of wound healing, thereby promoting the wound repair process.
1.5.7 transfer rate histology analysis- -identification of potential differential metabolites
The UPLC-TOF/MS is adopted for sample separation and data acquisition, each component can be well separated in a positive ion mode and a negative ion mode, the retention time and the peak area of each group are different, the model group, the example 5 and the example 7 are distributed in different quadrant areas, the separation degree is good, and the difference of serum metabolites of mice in each group is large. Meanwhile, mice were given potential differential metabolites common to example 5 and example 7 as shown in table 2.
TABLE 2 identification of potential differential metabolites common to example 5 and example 7
Note that: VIP variable projection importance of the substance on the set of comparison OPLS-DA models
FC: fold relationship of the substance between the comparative two experiments
P-the P-value obtained by t-test of the substance in the set of comparisons, P-value = probability that the hypothesis is correct but rejected = number of negative results/total number of results, is a probability of test on the sample data
The 9 differential metabolites selected are used as potential biomarkers in the wound healing process and mainly comprise 3-hydroxydecanoic acid, D-mannose, L-cystein, ethoxyquinoline, linolenic acid and derivatives thereof, fatty acyl, glycerolipid, glycerophospholipid and the like. Wherein D-mannose is an epimer of glucose, exists mainly in the form of an alpha-or beta-pyranose isomer, is directly utilized to synthesize glycoprotein in a human body, and has the effect of inhibiting inflammatory reaction in the wound healing process. The action of bioactive lipids occurs mainly in the inflammatory phase of the wound healing process. It has been further reported that topical use of fatty acid analogues and their receptor agonists can modulate inflammatory and immune responses during wound healing. As is clear from the results of fig. 6, the serum D-mannitol and fatty acid content in examples 5 and 7 were higher than those in the model group, the D-mannitol content in example 7 was higher, the fatty acid substance content in example 5 was higher, and examples 5 and 7 exert an effect of suppressing the inflammatory level in early wound healing by increasing the fatty acid level in serum, thereby exerting an effect of promoting wound healing.
The above embodiments represent only a few embodiments of the present invention, which are described in more detail and are not to be construed as limiting the scope of the present invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (2)
1. A composition for inhibiting inflammatory response, promoting angiogenesis and wound healing, comprising the following components in parts by weight:
0.1-100 parts of wheat oligopeptide, 0.1-100 parts of marine fish skin collagen oligopeptide, 0.1-100 parts of blood protein polypeptide, 0.01-2 parts of chamomile extract, 0.1-20 parts of beta-hydroxy-beta-methylbutyrate calcium, 0.01-3 parts of medlar powder, 0.001-1 part of zinc gluconate, 0.01-5 parts of casein phosphopeptide and 1-100 parts of water-soluble dietary fiber.
2. Use of a composition according to claim 1 for the manufacture of a medicament for promoting wound healing, for promoting angiogenesis in a wound healing process, for promoting angiogenesis and promoting vascular network remodeling and wound healing, for promoting cell adhesion, migration and proliferation at an early stage of wound healing, thereby promoting a wound repair process, and for exerting an effect of inhibiting inflammatory levels at an early stage of wound healing by increasing fatty acid levels in serum, thereby exerting an effect of promoting wound healing.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310064800.9A CN116036247B (en) | 2023-02-03 | 2023-02-03 | Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof |
PCT/CN2024/083281 WO2024160300A1 (en) | 2023-02-03 | 2024-03-22 | Composition for inhibiting inflammatory responses and promoting angiogenesis and wound healing, and use thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310064800.9A CN116036247B (en) | 2023-02-03 | 2023-02-03 | Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN116036247A CN116036247A (en) | 2023-05-02 |
CN116036247B true CN116036247B (en) | 2024-04-05 |
Family
ID=86113175
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310064800.9A Active CN116036247B (en) | 2023-02-03 | 2023-02-03 | Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN116036247B (en) |
WO (1) | WO2024160300A1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116036247B (en) * | 2023-02-03 | 2024-04-05 | 江中药业股份有限公司 | Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof |
Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101455405A (en) * | 2009-01-04 | 2009-06-17 | 江中药业股份有限公司 | Food or medicine capable of promoting wound healing after operation |
CN101461934A (en) * | 2009-01-04 | 2009-06-24 | 江中药业股份有限公司 | Application of small-molecule peptide in preparing medicament and food for promoting wound healing after operation |
CN102049037A (en) * | 2009-11-06 | 2011-05-11 | 李勇 | Application of ocean collagen peptide in process of preparing diabetes wound healing medicaments and foods |
CN103845721A (en) * | 2012-11-29 | 2014-06-11 | 江中药业股份有限公司 | Composition for control of radiation damage or chemotherapy damage and preparation method thereof |
CN103845722A (en) * | 2012-11-29 | 2014-06-11 | 江中药业股份有限公司 | Oligopeptide composition for control of radiation damage or chemotherapy damage and preparation method thereof |
CN105311061A (en) * | 2014-05-31 | 2016-02-10 | 陈光健 | Pharmaceutical composition having wound surface healing effect, preparation method and applications thereof |
CN106962923A (en) * | 2017-03-22 | 2017-07-21 | 深圳太太药业有限公司 | It is a kind of for it is physically weak, after being ill, the ocean dietary composition taken good care of of operation and preparation method thereof |
CN108339112A (en) * | 2016-12-30 | 2018-07-31 | 亚宝药业集团股份有限公司 | A kind of alimentation composition for promoting wound healing, bedsore reparation, postoperative stress ulcer healing |
CN109757734A (en) * | 2019-03-01 | 2019-05-17 | 上海傅克化学科技有限公司 | A kind of polypeptide oral liquor and preparation method thereof |
CN110585272A (en) * | 2019-10-23 | 2019-12-20 | 湖北精耕生物工程有限公司 | Bacteriostatic scar-removing liquid and preparation method thereof |
CN111436597A (en) * | 2020-04-01 | 2020-07-24 | 山东若尧特医食品有限公司 | Lipid chain peptide and production process thereof |
CN111632075A (en) * | 2020-05-27 | 2020-09-08 | 广州赛琅生物技术有限公司 | Exosome preparation for promoting skin wound healing and preparation method thereof |
CN111802646A (en) * | 2020-05-14 | 2020-10-23 | 河北康睿达脂质有限公司 | A nutritional composition for preventing muscle decay and its preparation method |
WO2022165700A1 (en) * | 2021-02-04 | 2022-08-11 | 吴达镕 | Polypeptide nutrition powder and preparation method therefor |
CN115634279A (en) * | 2022-04-14 | 2023-01-24 | 吉林农业科技学院 | Deer blood peptide hydrogel and application thereof in preparing medicine for treating diabetic skin injury |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19634959A1 (en) * | 1996-08-29 | 1998-03-05 | Karl Aulbach | Ointment for treating wounds, etc. |
FR2910815B1 (en) * | 2006-12-28 | 2010-10-29 | Expanscience Lab | COMPOSITION COMPRISING AN EXTRACT OF QUINOA SEEDS |
CN105077270A (en) * | 2015-07-16 | 2015-11-25 | 上海冬泽特医食品有限公司 | Nutrient supplemented composite powder as well as preparation method and use thereof |
JP7114458B2 (en) * | 2015-09-16 | 2022-08-08 | メタボリック・テクノロジーズ,インコーポレーテッド | Compositions and methods of use of β-hydroxy-β-methylbutyrate (HMB) to enhance recovery from soft tissue trauma |
CN116036247B (en) * | 2023-02-03 | 2024-04-05 | 江中药业股份有限公司 | Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof |
-
2023
- 2023-02-03 CN CN202310064800.9A patent/CN116036247B/en active Active
-
2024
- 2024-03-22 WO PCT/CN2024/083281 patent/WO2024160300A1/en unknown
Patent Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101461934A (en) * | 2009-01-04 | 2009-06-24 | 江中药业股份有限公司 | Application of small-molecule peptide in preparing medicament and food for promoting wound healing after operation |
CN101455405A (en) * | 2009-01-04 | 2009-06-17 | 江中药业股份有限公司 | Food or medicine capable of promoting wound healing after operation |
CN102049037A (en) * | 2009-11-06 | 2011-05-11 | 李勇 | Application of ocean collagen peptide in process of preparing diabetes wound healing medicaments and foods |
CN103845721A (en) * | 2012-11-29 | 2014-06-11 | 江中药业股份有限公司 | Composition for control of radiation damage or chemotherapy damage and preparation method thereof |
CN103845722A (en) * | 2012-11-29 | 2014-06-11 | 江中药业股份有限公司 | Oligopeptide composition for control of radiation damage or chemotherapy damage and preparation method thereof |
CN105311061A (en) * | 2014-05-31 | 2016-02-10 | 陈光健 | Pharmaceutical composition having wound surface healing effect, preparation method and applications thereof |
CN108339112A (en) * | 2016-12-30 | 2018-07-31 | 亚宝药业集团股份有限公司 | A kind of alimentation composition for promoting wound healing, bedsore reparation, postoperative stress ulcer healing |
CN106962923A (en) * | 2017-03-22 | 2017-07-21 | 深圳太太药业有限公司 | It is a kind of for it is physically weak, after being ill, the ocean dietary composition taken good care of of operation and preparation method thereof |
CN109757734A (en) * | 2019-03-01 | 2019-05-17 | 上海傅克化学科技有限公司 | A kind of polypeptide oral liquor and preparation method thereof |
CN110585272A (en) * | 2019-10-23 | 2019-12-20 | 湖北精耕生物工程有限公司 | Bacteriostatic scar-removing liquid and preparation method thereof |
CN111436597A (en) * | 2020-04-01 | 2020-07-24 | 山东若尧特医食品有限公司 | Lipid chain peptide and production process thereof |
CN111802646A (en) * | 2020-05-14 | 2020-10-23 | 河北康睿达脂质有限公司 | A nutritional composition for preventing muscle decay and its preparation method |
CN111632075A (en) * | 2020-05-27 | 2020-09-08 | 广州赛琅生物技术有限公司 | Exosome preparation for promoting skin wound healing and preparation method thereof |
WO2022165700A1 (en) * | 2021-02-04 | 2022-08-11 | 吴达镕 | Polypeptide nutrition powder and preparation method therefor |
CN115634279A (en) * | 2022-04-14 | 2023-01-24 | 吉林农业科技学院 | Deer blood peptide hydrogel and application thereof in preparing medicine for treating diabetic skin injury |
Non-Patent Citations (2)
Title |
---|
初元口服液;江中集团;百度百科;第1-3页 * |
心脑血管疾病探秘(三)血液垃圾清除剂-血肽;贝杉国际浙江省中心;微信;1-6 * |
Also Published As
Publication number | Publication date |
---|---|
CN116036247A (en) | 2023-05-02 |
WO2024160300A1 (en) | 2024-08-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Losi et al. | Fibrin-based scaffold incorporating VEGF-and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice | |
Shi et al. | Promoting Re-epithelialization in an oxidative diabetic wound microenvironment using self-assembly of a ROS-responsive polymer and P311 peptide micelles | |
CN116036247B (en) | Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof | |
WO2021103581A1 (en) | Skin topical composition having efficacy of promoting wound healing and/or scar repair | |
WO2016145237A1 (en) | Composition and methods to promote wound healing | |
EP0711171B1 (en) | A pharmaceutical or cosmetic composition comprising a colostrum fraction and its medical use | |
Liu et al. | Bioinspired Andrias davidianus-Derived wound dressings for localized drug-elution | |
WO1999044622A1 (en) | Inorganic nitrite and organic acid in combination as topical antiviral composition | |
CN113698452B (en) | Skin repair promoting peptide, preparation method and application thereof | |
Luo et al. | A synthetic leukotriene B4 receptor type 2 agonist accelerates the cutaneous wound healing process in diabetic rats by indirect stimulation of fibroblasts and direct stimulation of keratinocytes | |
EP3463395A1 (en) | Stem cell material, compositions, and methods of use | |
WO2021118292A2 (en) | Composition for wound healing, containing metal-organic framework | |
WO2008094061A1 (en) | Pharmaceutical and cosmetic compositions for accelerated healing of wounds and other surface damages | |
Chen et al. | A novel wound dressing based on a gold nanoparticle self-assembled hydrogel to promote wound healing | |
WO2016150356A1 (en) | New use of chlorogenic acid in preparation of medicine for promoting fibroblast proliferation | |
Polaka et al. | Development and biological evaluation of smart powder bandage for wound healing and dressing applications | |
CN105188731B (en) | For treating the protein s LURP-1 of eye disease | |
WO2019241985A1 (en) | Hydrogel, pharmaceutical composition comprising same, and application thereof | |
KR101820519B1 (en) | Use of sulglycotide for promoting skin-wound-healing, and composition for external application comprising the same | |
US11311484B2 (en) | Methods and compositions for treating skin afflictions | |
KR101885591B1 (en) | Pharmaceutical composition for wound healing containing Humanin or analogue thereof as an active ingredient | |
Pan et al. | Preparation of an antibacterial dressing for simultaneous delivery of polyhexamethylene biguanide and platelet-rich plasma, and evaluation of the dressing's ability to promote infected skin repair | |
Li et al. | Application of Bletilla striata polysaccharide hydrogel for wound healing among in diabetes | |
US20240207356A1 (en) | Composition and method for wound healing and repair of damaged nerves | |
LV13959B (en) | Adenylate deaminase containing hidrogel and use thereof for the treatment of dermal wounds (ulcers) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |