CN116531369A - Application of compound in medicine for promoting wound healing - Google Patents
Application of compound in medicine for promoting wound healing Download PDFInfo
- Publication number
- CN116531369A CN116531369A CN202310162691.4A CN202310162691A CN116531369A CN 116531369 A CN116531369 A CN 116531369A CN 202310162691 A CN202310162691 A CN 202310162691A CN 116531369 A CN116531369 A CN 116531369A
- Authority
- CN
- China
- Prior art keywords
- aminophenyl
- hydrochloride
- methyl
- compound
- medicament
- 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.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 50
- 230000029663 wound healing Effects 0.000 title claims abstract description 30
- 230000001737 promoting effect Effects 0.000 title claims abstract description 22
- 150000001875 compounds Chemical class 0.000 title claims abstract description 16
- -1 compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride Chemical class 0.000 claims abstract description 22
- 208000028990 Skin injury Diseases 0.000 claims abstract description 10
- 208000027418 Wounds and injury Diseases 0.000 claims description 30
- SPLSMCHCBCQKEV-UHFFFAOYSA-N [3-(3-methyl-5-oxo-4h-pyrazol-1-yl)phenyl]azanium;chloride Chemical compound Cl.O=C1CC(C)=NN1C1=CC=CC(N)=C1 SPLSMCHCBCQKEV-UHFFFAOYSA-N 0.000 claims description 27
- 206010052428 Wound Diseases 0.000 claims description 26
- 239000000499 gel Substances 0.000 claims description 15
- 239000000017 hydrogel Substances 0.000 claims description 7
- 239000011159 matrix material Substances 0.000 claims description 7
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 230000006378 damage Effects 0.000 claims description 5
- 239000002674 ointment Substances 0.000 claims description 5
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 3
- 102000008186 Collagen Human genes 0.000 claims description 3
- 108010035532 Collagen Proteins 0.000 claims description 3
- 229930182555 Penicillin Natural products 0.000 claims description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 3
- 239000000783 alginic acid Substances 0.000 claims description 3
- 229920000615 alginic acid Polymers 0.000 claims description 3
- 229960001126 alginic acid Drugs 0.000 claims description 3
- 235000010443 alginic acid Nutrition 0.000 claims description 3
- 150000004781 alginic acids Chemical class 0.000 claims description 3
- 229960004099 azithromycin Drugs 0.000 claims description 3
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 229920001436 collagen Polymers 0.000 claims description 3
- 229960005188 collagen Drugs 0.000 claims description 3
- 239000006071 cream Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 229960003276 erythromycin Drugs 0.000 claims description 3
- 229920002674 hyaluronan Polymers 0.000 claims description 3
- 229960003160 hyaluronic acid Drugs 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 229940049954 penicillin Drugs 0.000 claims description 3
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 230000000844 anti-bacterial effect Effects 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 21
- 230000035876 healing Effects 0.000 abstract description 8
- 230000033115 angiogenesis Effects 0.000 abstract description 4
- 210000004207 dermis Anatomy 0.000 abstract description 3
- 210000002615 epidermis Anatomy 0.000 abstract description 3
- 210000000651 myofibroblast Anatomy 0.000 abstract description 3
- 230000017423 tissue regeneration Effects 0.000 abstract description 3
- 230000010388 wound contraction Effects 0.000 abstract description 3
- 241000700159 Rattus Species 0.000 description 19
- 238000002474 experimental method Methods 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 210000003491 skin Anatomy 0.000 description 10
- 230000035755 proliferation Effects 0.000 description 7
- 229940099259 vaseline Drugs 0.000 description 7
- 239000007850 fluorescent dye Substances 0.000 description 6
- 230000005012 migration Effects 0.000 description 6
- 238000013508 migration Methods 0.000 description 6
- 230000010412 perfusion Effects 0.000 description 6
- 230000002980 postoperative effect Effects 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 5
- 230000008439 repair process Effects 0.000 description 5
- 208000014674 injury Diseases 0.000 description 4
- 208000002847 Surgical Wound Diseases 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 210000001339 epidermal cell Anatomy 0.000 description 3
- 208000018380 Chemical injury Diseases 0.000 description 2
- 208000034656 Contusions Diseases 0.000 description 2
- 208000001034 Frostbite Diseases 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- 206010072170 Skin wound Diseases 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 230000009519 contusion Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 231100000444 skin lesion Toxicity 0.000 description 2
- 206010040882 skin lesion Diseases 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 1
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N Aminophenazone Chemical compound O=C1C(N(C)C)=C(C)N(C)N1C1=CC=CC=C1 RMMXTBMQSGEXHJ-UHFFFAOYSA-N 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- DAYLJWODMCOQEW-TURQNECASA-O NMN(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(O)=O)O2)O)=C1 DAYLJWODMCOQEW-TURQNECASA-O 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102100040990 Platelet-derived growth factor subunit B Human genes 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229960000212 aminophenazone Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000002555 anti-neurodegenerative effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229960004787 becaplermin Drugs 0.000 description 1
- HYNPZTKLUNHGPM-KKERQHFVSA-N becaplermin Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc2cnc[nH]2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]5CCCN5C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]6CCCN6C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]7CCCN7C(=O)[C@H](Cc8c[nH]c9c8cccc9)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)N HYNPZTKLUNHGPM-KKERQHFVSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008081 blood perfusion Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- DJGAAPFSPWAYTJ-UHFFFAOYSA-M metamizole sodium Chemical compound [Na+].O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 DJGAAPFSPWAYTJ-UHFFFAOYSA-M 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 229960005222 phenazone Drugs 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000028016 temperature homeostasis Effects 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
-
- 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
-
- 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)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of a compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride in a medicament for promoting wound healing. The invention discovers that the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride can promote epithelialization, angiogenesis and myofibroblast-induced wound contraction to accelerate healing of epidermis and dermis and promote tissue repair. The compound has the effect of promoting wound healing, and can be used for preparing medicine for treating skin injury.
Description
Technical Field
The invention relates to the technical field of pharmacy, in particular to application of a compound in a medicament for promoting wound healing.
Background
The skin is not only an effective barrier against all external factors including microorganisms, but also has other important physiological functions including thermoregulation, humoral regulation, sensory detection and vitamin synthesis. Therefore, when the skin is wounded, rapid repair is required so that the skin can recover its important functions as soon as possible. At present, the treatment of acute wounds and surgical wounds is mainly carried out by systemic antibiotics and dressing treatment. However, these methods generally have limited benefits on healing results and, therefore, non-healing or wound recurrence is still common. The current medicines for skin healing have limited treatment means, and only(Becaplermin) is the only FDA (U.S. food and drug administration) approved drug for the treatment of chronic skin wounds. But the clinical application of the medicine also has obvious safetyIntegrity problems. Thus, there remains a great need in the clinic for new and useful drugs that can rapidly promote healing of skin wounds.
The 2-hydro-pyran and 4-hydro-pyran ring heterocyclic backbones are structural parent cores found in natural compounds with a wide range of significant biological activities, such as anti-neurodegenerative, anti-cancer, cytotoxic, anti-HIV, anti-malarial, antibacterial, anti-hyperglycemic and anti-dyslipidemia, such as Alzheimer's, parkinson's and Huntington's disease. Wherein the 1-phenyl-3-methyl-5-pyrazolone is used for synthesizing pyrazolone antipyretic analgesic such as analgin, antipyrine and aminopyrine. However, no report or application of the 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride in the medicine for wound healing is available.
Disclosure of Invention
The invention provides a new application of a compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride as a medicament for promoting wound healing for the first time, and test results show that the compound has obvious effect of promoting skin repair as the medicament for promoting wound healing.
The technical scheme of the invention is as follows: use of a compound in a medicament for promoting wound healing, wherein the compound is 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride, and the compound has the following structure:
further, the wound refers to physical injury such as incised wound, contusion, burn, frostbite, burn, mechanical injury, suture wound after operation and/or chemical injury of skin.
A medicament for the treatment of skin lesions, said medicament comprising the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride.
Further, the medicament further comprises a pharmaceutically acceptable carrier or excipient.
Further, the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride has a concentration of 50nM in the carrier.
Further, the medicine is an external application product, and the external application product comprises one of ointment, cream, emulsion, patch, powder or film.
Further, when the medicine is a paste, the preparation method is that the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride is uniformly mixed with Vaseline to obtain the ointment for treating skin injury, wherein the concentration of the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride in carrier Vaseline is 50nM.
A pharmaceutical composition for promoting wound healing is prepared from 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride and available pharmaceutical excipients.
Further, the pharmaceutical composition is a liquid, paste, gel, dressing or spray.
Further, the gel is selected from cellulose, hyaluronic acid, alginic acid, collagen or a medically available hydrogel as a matrix.
When the hydrogel is used as a matrix, the hydrogel matrix is boiled and sterilized for 30min, then gel with the mass concentration of 2 percent of compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride being more than 2 percent and less than or equal to 6 percent of compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride is prepared under the condition of 20 ℃.
Further, the gel is a mixed gel formed by adding 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride as a compound to azithromycin, erythromycin, penicillin or a pharmaceutically acceptable antibacterial agent.
Compared with the prior art, the invention provides a new application of the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride as a medicament for promoting wound healing for the first time. The invention discovers that the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride can promote epithelialization, angiogenesis and myofibroblast-induced wound contraction to accelerate healing of epidermis and dermis and promote tissue repair. In vitro experiments of HaCats human immortalized epidermal cell cells and animal results of SD rat skin injury model show that the medicine has obvious effect of promoting skin repair as a medicine for promoting wound healing. Therefore, the compound has the effect of promoting wound healing, and can be used for preparing medicines for treating skin injury. The invention provides a medicine capable of rapidly treating skin injury wound surface repair, which has strong pertinence and remarkable curative effect, can rapidly heal wounds, and provides a new medicine for treating skin injury.
Drawings
FIG. 1 is the effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on Hacath cell proliferation, and A in FIG. 1 is a CCK proliferation toxicity effect experiment; b in fig. 1 is a graph of Edu fluorescent staining results; c in fig. 1 is a Edu fluorescent staining statistical plot; d in fig. 1 is a scratch test result.
FIG. 2 is a graph showing the effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on HUVEC cell migration proliferation. A in fig. 2 is a Transwell migration experiment and statistics of results thereof; b in FIG. 2 is a statistical graph of Edu fluorescent staining results and results thereof.
Fig. 3 is a graph of wound healing experiments and statistics of rats.
Fig. 4 is a laser doppler scan image of a rat wound and a statistical graph thereof.
Fig. 5 is a statistical plot of the wound area of rats.
Figure 6 is a doppler perfusion imaging statistical plot.
FIG. 7 is a graph showing the effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on wound healing after surgery in rats. A in fig. 7 is a 7-day postoperative wound healing condition of a rat, B in fig. 7 is a statistical graph of the postoperative survival skin of the rat, C in fig. 7 is a postoperative blood flow perfusion amount of the rat, and D in fig. 7 is a statistical graph of doppler perfusion imaging.
Detailed Description
The invention is further illustrated by the following figures and examples, which are not intended to be limiting.
Example 1: use of a compound in a medicament for promoting wound healing, wherein the compound is 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride, and the compound has the following structure:
further, the wound refers to physical injury such as incised wound, contusion, burn, frostbite, burn, mechanical injury, suture wound after operation and/or chemical injury of skin.
Example 2: a medicament for the treatment of skin lesions, said medicament comprising the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride.
Further, the medicament further comprises a pharmaceutically acceptable carrier or excipient.
Further, the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride has a concentration of 50nM in the carrier.
Further, the medicine is an external application product, and the external application product comprises one of ointment, cream, emulsion, patch, powder or film.
Further, when the medicine is a paste, the preparation method is that the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride is uniformly mixed with Vaseline to obtain the ointment for treating skin injury, wherein the concentration of the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride in carrier Vaseline is 50nM.
Example 3: a pharmaceutical composition for promoting wound healing is prepared from 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride and available pharmaceutical excipients.
Further, the pharmaceutical composition is a liquid, paste, gel, dressing or spray.
Further, the gel is selected from cellulose, hyaluronic acid, alginic acid, collagen or a medically available hydrogel as a matrix.
When the hydrogel is used as a matrix, the hydrogel matrix is boiled and sterilized for 30min, then gel with the mass concentration of 2% of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride is prepared under the condition of 20 ℃, and nicotinamide mononucleotide is added to prepare gel with the mass concentration of 5% of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride.
Further, the gel is a mixed gel formed by adding 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride as a compound to azithromycin, erythromycin, penicillin or a pharmaceutically acceptable antibacterial agent. Example 4:2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on hacabas cells.
HaCaTs cells are human immortalized epidermal cells, are non-tumor-derived human normal skin immortalized keratinocyte cell lines, have similar differentiation characteristics to normal human keratinocyte cells and have no tumor characteristics. In vitro experiments were performed using hacabas human immortalized epidermal cells to verify the effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on hacabas cells. FIG. 1 is the effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on Hacath cell proliferation, and A in FIG. 1 is a CCK proliferation toxicity effect experiment; b in fig. 1 is a graph of Edu fluorescent staining results; c in fig. 1 is a Edu fluorescent staining statistical plot; d in fig. 1 is a scratch test result.
A in FIG. 1 is a CCK-8 experiment to verify whether 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride has cytotoxicity to HaCaTs cells, CCK-8 activity is measured after drug administration with gradient concentration of 0-1000 ng/mL for 24h, and the experiment result shows that 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride has no obvious cytotoxicity to HaCaTs cells. In addition, whether the medicine can promote the proliferation of HaCaTs cells is detected by using Edu staining and scratch experiments, and the result shows that compared with a control group, the cell proliferation of a 50ng/mL administration group has a remarkable promotion effect, and scratches basically disappear after 48 hours.
Example 5: effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on migration of HUVEC cells.
HUVEC cells refer to human umbilical vein endothelial cells in human body, and whether the medicine can promote the migration and proliferation of HUVEC cells is detected by using a Transwell migration experiment and an edu experiment, the result is shown in figure 2, and the figure 2 shows the influence of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on the migration and proliferation of HUVEC cells. A in fig. 2 is a Transwell migration experiment and statistics of results thereof; b in FIG. 2 is a statistical graph of Edu fluorescent staining results and results thereof. The results in FIG. 2 show that the 50ng/mL administration group has significant cell migration promoting effect and proliferation effect compared with the control group, and the in vitro level can promote wound angiogenesis.
Example 6: effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on wound healing in vivo.
After shaving and sterilizing SD rats, two full-thickness wounds of 20mm diameter were made on both sides of the back, and the control group was treated by covering the wounds with sterile, transparent dressing for the first three days. The vaseline group is treated by covering with sterile transparent application for the first three days after covering with vaseline, and applying once every two days. The treatment mode of the drug group is that after the wound is covered by Vaseline containing 100nmol/g of drug, the wound is covered by sterile transparent application in the first three days, and the wound is applied every two days, and wound healing condition in 21 days is observed and recorded. FIG. 3 is a graph of the wound healing experiments and statistics of rats;
FIG. 4 laser Doppler scanning imaging of rat wounds and a statistical graph thereof; FIG. 5 is a statistical chart of the rat wound area experiment; figure 6 is a doppler perfusion imaging statistical plot. The results of the experiments in fig. 3-6 were observed and indicated that the drug group showed significant wound reduction at day 7, and that the combination with the doppler scanner showed substantial wound healing after 21 days of the drug group. The results show that the external application of the 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride has the effect of obviously promoting the wound healing of rats.
Example 7: effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on healing of surgical wounds in vivo.
After shaving and sterilizing SD rats, a full-thickness wound of 25 x 110mm was closed on the back, physiological saline was injected every other day in a control treatment mode, 50nmol/g of physiological saline was injected every other day in a drug group treatment mode, and wound healing was observed and recorded within 21 days. FIG. 7 is a graph showing the effect of 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on wound healing after surgery in rats. A in fig. 7 is a 7-day postoperative wound healing condition of a rat, B in fig. 7 is a statistical graph of the postoperative survival skin of the rat, C in fig. 7 is a postoperative blood flow perfusion amount of the rat, and D in fig. 7 is a statistical graph of doppler perfusion imaging.
The results of fig. 7 were observed to show that the drug-applied group was significantly better than the control group in terms of surgical wound necrosis at day 7, and that the results of the combination with the doppler scanner showed that the effect of blood perfusion at the wound was significantly better than the control group after day 7. The results show that the injection of the 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride has the effect of obviously promoting the wound healing of rats.
In view of the above, the invention provides a new application of the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride as a medicament for promoting wound healing for the first time. The invention discovers that the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride can promote epithelialization, angiogenesis and myofibroblast-induced wound contraction to accelerate healing of epidermis and dermis and promote tissue repair. The invention provides a medicine capable of rapidly treating skin injury wound surface repair, which has strong pertinence and remarkable curative effect, can rapidly heal wounds, and provides a new medicine for treating skin injury.
Claims (10)
1. Use of a compound in a medicament for promoting wound healing, characterized in that: the compound is 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride.
2. The use according to claim 1, characterized in that: the wound refers to physical, mechanical and/or chemical damage to the skin.
3. A medicament for treating skin injury, characterized in that: the medicament comprises the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride.
4. A medicament according to claim 3, characterized in that: the medicament further comprises a pharmaceutically acceptable carrier or excipient.
5. A medicament according to claim 4, characterized in that: the concentration of the compound 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride on the carrier is 50nM.
6. A medicament according to claim 4, characterized in that: the medicine is an external application product, and the external application product comprises one of ointment, cream, emulsion, patch, powder or film.
7. A pharmaceutical combination for promoting wound healing, characterized in that: the pharmaceutical composition is prepared from 2- (3-aminophenyl) -5-methyl-2, 4-dihydropyrazol-3-one hydrochloride and available pharmaceutical excipients.
8. The pharmaceutical combination according to claim 7, wherein: the pharmaceutical composition is a liquid, a paste, a gel, a dressing or a spray.
9. The pharmaceutical combination according to claim 8, wherein: the gel is prepared from cellulose, hyaluronic acid, alginic acid, collagen or medical hydrogel as matrix.
10. The pharmaceutical combination according to claim 8, wherein: the gel is a mixed gel formed by adding 2- (3-aminophenyl) -5-methyl-2, 4-dihydro-pyrazol-3-one hydrochloride into azithromycin, erythromycin, penicillin or a pharmaceutically acceptable antibacterial medicament.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310162691.4A CN116531369A (en) | 2023-02-24 | 2023-02-24 | Application of compound in medicine for promoting wound healing |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310162691.4A CN116531369A (en) | 2023-02-24 | 2023-02-24 | Application of compound in medicine for promoting wound healing |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116531369A true CN116531369A (en) | 2023-08-04 |
Family
ID=87449443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310162691.4A Pending CN116531369A (en) | 2023-02-24 | 2023-02-24 | Application of compound in medicine for promoting wound healing |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116531369A (en) |
-
2023
- 2023-02-24 CN CN202310162691.4A patent/CN116531369A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2641614B1 (en) | Pharmaceutical preparation integrated with microneedles for skin treatment | |
| CN106620653B (en) | It is a kind of to be used to treat composition of skin wound and preparation method thereof | |
| JPH07505378A (en) | Wound treatment treatment for fibrotic disorders | |
| DE202008018583U1 (en) | Drug delivery system for local analgesia, local anesthesia or nerve block | |
| CN101491498A (en) | aFGF liposome, preparation method and use thereof | |
| US20230218712A1 (en) | Topical application of polypeptide in the treatment of skin damage | |
| CN110974781A (en) | Gel for repairing skin wound | |
| CN101152568A (en) | Polypeptide combination preparations having functions of accelerating angiogenesis, organ reactivation and wound healing | |
| KR20150128481A (en) | Composition for application of skin comprising of extracellular matrix and thermo sensitive macromolecule | |
| CN108685892B (en) | Application of chlorogenic acid and composition thereof in preparing medicine for treating squamous cell carcinoma | |
| KR102158969B1 (en) | Composition for treating intractable ulcer comprising substance P | |
| CN116531369A (en) | Application of compound in medicine for promoting wound healing | |
| KR20210093748A (en) | Neurotoxin for use in minimizing scarring | |
| CN114129714A (en) | Medicinal preparation and preparation method and application thereof | |
| RU2209074C2 (en) | Method for treating burns | |
| JP7364839B2 (en) | Use of cannaflavin A in the manufacture of pharmaceutical products promoting wound healing | |
| CN114948852B (en) | Microneedle system for brain disease diagnosis and treatment and preparation method thereof | |
| WO2023102847A1 (en) | Ws635 uses thereof in medicine | |
| CN112190687B (en) | Medicine for reducing skin wound scar and application thereof | |
| RU2809091C1 (en) | Subcutaneous biodegradable implant for delayed hemostimulation of cancer patients | |
| CN111773277A (en) | Preparation method and application of pawpaw total triterpene hydrogel | |
| TW202415401A (en) | Use of bletilla formosana (hayata) schltr. extract for the manufacture of a pharmaceutical composition for promoting chronic wound healing | |
| CN117343130A (en) | Polypeptide LX with chronic refractory skin wound repair promoting activity and application thereof | |
| CN117860843A (en) | Use of bletilla striata extract for preparing pharmaceutical composition for promoting chronic wound healing | |
| JP2023552515A (en) | Compositions and methods for treating wounds |
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 |