CN118161487A - Application of benzisoxazole derivative in preparing wound healing promoting medicine - Google Patents
Application of benzisoxazole derivative in preparing wound healing promoting medicine Download PDFInfo
- Publication number
- CN118161487A CN118161487A CN202410306648.5A CN202410306648A CN118161487A CN 118161487 A CN118161487 A CN 118161487A CN 202410306648 A CN202410306648 A CN 202410306648A CN 118161487 A CN118161487 A CN 118161487A
- Authority
- CN
- China
- Prior art keywords
- wound healing
- promoting
- benzisoxazole
- medicament
- bamb
- 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
- 230000029663 wound healing Effects 0.000 title claims abstract description 40
- 150000008316 benzisoxazoles Chemical class 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 title claims abstract description 33
- 230000001737 promoting effect Effects 0.000 title claims abstract description 25
- 206010052428 Wound Diseases 0.000 claims description 19
- 208000027418 Wounds and injury Diseases 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 201000004624 Dermatitis Diseases 0.000 claims description 3
- 206010053615 Thermal burn Diseases 0.000 claims description 3
- 208000025865 Ulcer Diseases 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 231100000397 ulcer Toxicity 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 229940040145 liniment Drugs 0.000 claims description 2
- 239000000865 liniment Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000003357 wound healing promoting agent Substances 0.000 claims 1
- 210000002950 fibroblast Anatomy 0.000 abstract description 29
- 210000004027 cell Anatomy 0.000 abstract description 22
- 210000003953 foreskin Anatomy 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 12
- 230000005012 migration Effects 0.000 abstract description 12
- 238000013508 migration Methods 0.000 abstract description 12
- 230000009545 invasion Effects 0.000 abstract description 9
- 230000001684 chronic effect Effects 0.000 abstract description 7
- 210000001161 mammalian embryo Anatomy 0.000 abstract description 6
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 abstract description 3
- 206010070863 Toxicity to various agents Diseases 0.000 abstract description 3
- -1 compound benzisoxazole derivative Chemical class 0.000 abstract description 3
- 230000033001 locomotion Effects 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- IEPCQLHHUYRTEY-UHFFFAOYSA-N n-(1,2-benzoxazol-3-yl)-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC1=NOC2=CC=CC=C12 IEPCQLHHUYRTEY-UHFFFAOYSA-N 0.000 abstract 3
- 239000007853 buffer solution Substances 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 5
- 239000008055 phosphate buffer solution Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000006285 cell suspension Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 229940000406 drug candidate Drugs 0.000 description 3
- 239000003777 experimental drug Substances 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 231100000820 toxicity test Toxicity 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000007605 air drying Methods 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 230000035606 childbirth Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 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 1
- 238000010186 staining Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000037314 wound repair Effects 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
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to application of benzisoxazole derivatives in preparing medicaments for promoting wound healing, and discovers that the benzisoxazole derivatives BAMB-4 show remarkable migration and invasion activity on human foreskin fibroblast HFF-1 after acting for 24-48 hours at a concentration lower than 2 mu M, which indicates that BAMB-4 can rapidly improve the movement capacity of cells; meanwhile, the benzisoxazole derivative BAMB-4 has no drug toxicity trend to human foreskin fibroblast HFF-1 and mouse embryo fibroblast L-929 under the concentration of 200 mu m/L, and has very high safety; therefore, the compound benzisoxazole derivative provided by the invention can realize the effect of promoting wound healing safely and without toxic or side effects in a large dosage range, and particularly has the remarkable effect of reducing chronic wound healing time for diabetics with poor wound healing capacity.
Description
Technical Field
The invention belongs to the technical field of medicines and preparations, and particularly relates to application of benzisoxazole derivatives in preparation of medicines for promoting wound healing.
Background
The skin is used as the largest organ of human body, plays a vital role in protecting human organs and tissues, preventing infection, maintaining water and electrolyte balance, regulating body temperature and the like, and also maintains the stability of the environment in the human body. The skin is quite fragile, and is inevitably wounded in daily life. Skin wounds can not only cause pain to the patient and affect the patient's health, but also affect the patient's mental and mental health. Wound healing is an extremely complex and dynamic process, and how to effectively promote wound healing and prevent infection is an important subject in the field of wound repair. Wound self-repair and tissue regeneration are complex cellular processes involving interactions between GFs, chemokines, cytokines, and other signaling molecules. The wound healing process is continuous and interdigitated and can be roughly divided into 4 phases: the proliferation stage is the most critical stage, and mainly consists of keratinocytes, vascular endothelial cells and fibroblasts, so that the angiogenesis in the stage is extremely difficult for healing of chronic wounds, such as the process of revascularization in wounds of diabetics is very slow, the surface area of blood vessels, branch connection numbers, total blood vessel length and total branch numbers in wounds are obviously reduced, angiogenesis can effectively support wound closure, and vascular lesions are one of causes of difficult healing of chronic wounds.
At present, the treatment of wounds and wound surfaces mainly comprises treatment means such as laser, treatment auxiliary materials, negative pressure treatment, skin transplantation and the like, the clinical application is limited, and the effect is not ideal especially for chronic wounds. Therefore, development of new drugs for accelerating wound healing, especially chronic wound healing for diabetics and the like, is a highly-needed problem. Based on the fact that the development difficulty of new drugs for promoting wound healing is high, the wound healing activity is still low, and cytotoxicity is difficult to control, the development of new applications by adopting known drugs is a rapid and effective drug development way.
Disclosure of Invention
Aiming at the prior art problems, the invention provides application of benzisoxazole derivatives in preparing a medicine for promoting wound healing, and the benzisoxazole derivatives can obviously improve migration and invasion capacities of cells and can be used for promoting wound healing of diabetics or non-diabetics.
In a first aspect, the invention provides application of benzisoxazole derivatives in preparing a medicine for promoting wound healing, wherein the benzisoxazole derivatives have a molecular structural general formula:
Wherein R is selected from one or more substituents of hydrogen atoms, halogen and C1-6 alkyl, and the substituent is mono-substituted or multi-substituted.
Further, the molecular structural formula of the benzisoxazole derivative comprises:
further, the molecular structural formula of the benzisoxazole derivative comprises:
preferably, the benzisoxazole derivative is benzo [ d ] isoxazol-3-yl) -4-methylbenzamide (BAMB-4), and the molecular structural formula is as follows:
further, the medicament comprises promoting wound healing of diabetics.
Further, the medicament comprises promoting wound healing in non-diabetic patients.
In a second aspect, the invention also provides a medicament for promoting wound healing, which comprises the benzisoxazole derivative, the geometric isomer thereof or the pharmaceutically acceptable salt and/or the solvate and/or the hydrate thereof.
Further, the medicament also comprises pharmaceutically acceptable auxiliary materials.
Further, the dosage forms of the medicament comprise suspension, granules, capsules, powder, tablets, emulsion, solution, dripping pills, injection, aerosol, gel, patch, drops or liniment, and other non-enumerated indications are also applicable in the scope of the above dosage forms.
Further, the medicament comprises promoting wound healing of diabetics.
The pharmaceutical indications include wounds, wounds of diabetics or wounds of non-diabetics, but are not limited to the above listed indications, and other non-listed indications within the above indicated range are equally applicable;
Further, wounds of the non-diabetic patients include burns, scalds, ulcers, dermatitis, childbirth, but are not limited to the above-listed indications, and other non-listed indications within the above-listed indications are equally applicable.
Compared with the prior art, the invention has the following beneficial effects:
the invention develops the new application of the benzisoxazole derivatives, and discovers that the benzisoxazole derivatives can promote the migration and invasion of cells, in particular to the benzisoxazole derivatives have obvious migration and invasion effects on human foreskin fibroblast HFF-1, wherein the compound BAMB-4 has obvious activity on the migration and invasion of human foreskin fibroblast HFF-1 at the concentration lower than 2 mu M, therefore, the benzisoxazole derivatives can obviously improve the migration capacity of human foreskin fibroblast HFF-1 at the extremely low concentration, and improve the migration and invasion penetration capacity of cells; meanwhile, the benzisoxazole derivative BAMB-4 has no drug toxicity trend to human foreskin fibroblast HFF-1 and mouse embryo fibroblast L-929 under the concentration of 200 mu m/L, and has very high safety; therefore, the compound benzisoxazole derivative provided by the invention can be used for rapidly improving the movement capability of cells, is safe in a large dosage range, has no toxic or side effect, realizes the effect of promoting wound healing, accelerates the wound healing, can further reduce the chronic wound healing time especially for diabetics with poor wound healing capability, and can be widely applied to promoting the wound healing of wounds, burns, scalds, ulcers, dermatitis, chronic wounds and childbirth.
Drawings
FIG. 1 is an in vitro toxicity test of benzisoxazole derivative BAMB-4 of the present invention on human foreskin fibroblast HFF-1.
FIG. 2 is an in vitro toxicity test of benzisoxazole derivative BAMB-4 of the invention on mouse embryonic fibroblast L-929.
FIG. 3 is a graph showing migration of benzisoxazole derivative BAMB-4 of the present invention to human foreskin fibroblast HFF-1.
FIG. 4 is a graph showing the statistical results of the migration of benzisoxazole derivative BAMB-4 of the present invention to human foreskin fibroblast HFF-1.
FIG. 5 is a graph showing the invasion of benzisoxazole derivative BAMB-4 of the present invention on human foreskin fibroblast HFF-1.
FIG. 6 is a graph showing statistical results of invasion of human foreskin fibroblast HFF-1 by benzisoxazole derivative BAMB-4 according to the present invention.
Detailed Description
The experimental methods of the present invention, in which specific conditions are not specified in the following examples, are generally conducted under conventional conditions or under conditions recommended by the manufacturer. The various chemicals commonly used in the examples are commercially available.
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 in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The terms "comprising" and "having" and any variations thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, apparatus, article, or device that comprises a list of steps is not limited to the elements or modules listed but may alternatively include additional steps not listed or inherent to such process, method, article, or device.
The present invention will be further described in detail with reference to the following embodiments, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the description is only illustrative and is not intended to limit the scope of the invention. In addition, in the following description, descriptions of well-known structures and techniques are omitted so as not to unnecessarily obscure the present invention.
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.
The specific examples of the present invention were carried out using benzo [ d ] isoxazol-3-yl) -4-methylbenzamide (BAMB-4) having the following molecular structural formula:
example 1CCK8 cytotoxicity assay
(1) The experimental object: human foreskin fibroblast HFF-1, mouse embryo fibroblast L-929;
(2) Experimental drugs: BAMB-4, solvent DMSO (dimethyl sulfoxide);
(3) The experimental method comprises the following steps:
the first pm plating: collecting logarithmic phase cells, regulating cell suspension concentration, adding 90uL,5000 human foreskin fibroblast HFF-1 and 8000 mouse embryo fibroblast L-929 into each hole;
Dosing the next morning: adding 10 mu L of medicine with concentration gradient into each hole, arranging 3 compound holes for each medicine concentration, placing into 5% CO 2, and incubating in a 37 ℃ incubator;
plate collection after 48h of dosing: firstly, carrying out visual observation under an inverted microscope, then adding 10uLCCK solution into each hole, and after incubation for 1h at 37 ℃, stopping the reaction;
OD value detection: detecting the light absorption value of each hole at the wavelength of 450nm of the enzyme label instrument, and calculating the relative survival rate or the drug inhibition rate of the cells according to formulas (1) and (2);
drug inhibition%1-relative survival%
The experiment uses a cell-free culture medium as a blank control group, a DMSO solution with the same dilution ratio as that of the compound BAMB-4 is added into each hole as a negative control group, and the compound BAMB-4 is used as a compound experiment group.
The effect of compound BAMB-4 on the growth activities of human foreskin fibroblast HFF-1 and mouse embryo fibroblast L-929 was tested according to the above-described experimental method (CCK 8 toxicity test, 48 h), and the calculated results are shown in FIG. 1 and FIG. 2, and the compound BAMB-4 has no drug toxicity trend to human foreskin fibroblast HFF-1 and mouse embryo fibroblast L-929 under the concentration of 200 μm/L, and IC 50 can not be detected.
Example 2 cell migration Capacity experiment (cell scratch experiment)
(1) The experimental object: human foreskin fibroblast HFF-1;
(2) Experimental drugs: BAMB-4, solvent DMSO (dimethyl sulfoxide);
(3) The experimental method comprises the following steps:
Before plating, a marker pen thin head is used for uniformly drawing a transverse line behind a 6-hole plate, a straight ruler is used for comparison, a hole is traversed approximately every 0.5-1 cm, three lines are generally drawn, the line is sequentially named as a line, b and c, the line is traversed to the center, two other lines are drawn at equal intervals on two sides of the line b, six-hole plates are plated, 2mL of complete culture medium containing 10% FBS (fetal bovine serum) is added into each hole, 2X 10 6 cells are respectively arranged in 2 multiple holes, the culture is carried out for about 24 hours, the cell number is preferably equal to or more than 90% after overnight, the cover of the hole plate is properly adjusted, the old culture medium is sucked off the next day, a straight ruler vertical b line frame is arranged on the hole plate, a 200uL gun head is used for tightly clinging to the straight ruler, cell scratch lines are manufactured, similarly, two parallel lines are respectively drawn on two sides of the line at equal intervals, line 2 and line 3 are respectively named as line 1, cell buffer solution containing 10% FBS (fetal bovine serum) is diluted to 1X 1 time, cell buffer solution is used for 3 times, cell buffer solution containing 5% of buffer solution is added into PBS (fetal serum is diluted to be removed), the buffer solution is completely filled into the buffer solution, and the buffer solution is added into the buffer solution for complete culture medium for 5-containing 10% of FBS (buffer solution) and the buffer solution is completely cultured for 5 mu 0M, and then the buffer solution is added for 5 mu 0M solution is completely after the buffer solution is added for 5M and is added into the buffer solution for 5 until the buffer solution is completely and 5 solution after 5 solution is completely and 5M and 5 buffer solution is completely buffer until 5 buffer solution is completely buffer solution is added 4 and 5 is prepared.
The migration ability test was performed according to the above test method, and the obtained results are shown in fig. 3 and fig. 4, where the test results indicate that, compared with Control (DMSO solution), low concentration (1 μm, 2 μm) of compound BAMB-4 can significantly improve the movement and migration ability of human fibroblast HFF-1 after 24 hours of action, and promote healing of scratch wound, and P <0.001 indicates that there is a significant difference between the Control and dosing groups (concentrations 1 μm/L and 2 μm/L) without dosing.
Example 3 cell migration Capacity experiment (cell invasion Transwell experiment)
(1) The experimental object: human foreskin fibroblast HFF-1;
(2) Experimental drugs: BAMB-4, solvent DMSO (dimethyl sulfoxide);
(3) The experimental method comprises the following steps:
Preparing a cell suspension: digesting cells, centrifuging after stopping digestion, discarding culture solution, washing with PBS (phosphate buffer solution) for 1 time, re-suspending in serum-free culture medium, and adjusting cell density to proper concentration (the plate density of human foreskin fibroblast HFF-1 is 1×10 5/200 μL);
inoculating cells: each cell is provided with a negative Control group Control (DMSO with the same dilution ratio as that of the compound BAMB-4 is added), a dosing group (working concentration of the compound BAMB-4 of human foreskin fibroblast HFF-1 is 0.1 mu M and 0.2 mu M), 3 compound holes are respectively formed in each group, a proper amount of cell suspension is taken according to cell density, a proper amount of 10% BSA is added to make the final percentage of the cell suspension be 0.1%, then the compound BAMB-4 is added, and finally DMEM is used for supplementing, so that the total volume of each hole is 200 mu L, after uniform mixing, the mixture is gently and uniformly added into a Transwell upper chamber, 800 mu L of culture medium containing 20% FBS is generally added into a 24-hole plate lower chamber immediately, and plates are harvested after 48 hours of dosing;
Cell staining: taking out Transwell chamber, discarding culture solution in the well, gently wiping off non-migrated cells in the upper chamber with cotton bud, placing into clean 24-well plate, washing 1 time with 1 XPBS, fixing with methanol for 30min, sucking methanol, air drying the chamber in fume hood, dyeing for 20min with 0.1% crystal violet, sucking off recovered crystal violet, washing 1 time with PBS, sucking PBS, and air drying in fume hood.
And (3) result statistics: the cells were observed under 5X microscope, photographed, counted and statistically plotted, and the results are shown in fig. 5 and 6, wherein compound BAMB-4 can significantly promote migration and invasion capacity of human foreskin fibroblasts HFF-1 at 0.1 μm and 0.2 μm, P <0.001 is shown, indicating that there is a significant difference between the control group without drug addition and the drug addition group (concentration 0.1 μm/L and 0.2 μm/L), indicating that compound BAMB-4 can promote wound healing, enhance wound healing capacity, and accelerate wound healing rate.
It should be noted that, in the present specification, specific features, structures, materials, or characteristics may be arbitrarily combined, and in order to simplify the description, all possible combinations of the features in the foregoing embodiments are not described, and those skilled in the art may combine and combine the features of the different embodiments and the different embodiments described in the present specification without contradiction.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the 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 (10)
1. The application of the benzisoxazole derivative in preparing the medicine for promoting wound healing is characterized in that the benzisoxazole derivative has a molecular structural general formula:
Wherein R is selected from one or more substituents of hydrogen atoms, halogen and C1-6 alkyl, and the substituent is mono-substituted or multi-substituted.
2. The use of benzisoxazole derivatives according to claim 1 in the preparation of a wound healing promoting medicament, wherein the benzisoxazole derivatives have a molecular structural formula comprising:
3. the use of benzisoxazole derivatives according to claim 1 in the preparation of a wound healing promoting medicament, wherein the benzisoxazole derivatives have a molecular structural formula comprising:
4. The use of benzisoxazole derivatives according to claim 1 in the preparation of a medicament for promoting wound healing, wherein the medicament comprises promoting wound healing in diabetics.
5. The use of benzisoxazole derivatives in the preparation of a medicament for promoting wound healing according to claim 1, wherein the medicament comprises the promotion of wound healing in non-diabetic patients.
6. A medicament for promoting wound healing, characterized in that the medicament comprises a benzisoxazole derivative according to any one of claims 1 to 5 and its geometrical isomer or a pharmaceutically acceptable salt and/or a solvate and/or a hydrate thereof.
7. The wound healing promoting drug according to claim 6, wherein the drug further comprises pharmaceutically acceptable excipients.
8. The wound-healing-promoting agent according to claim 6, wherein the dosage form of the agent comprises a suspension, a granule, a capsule, a powder, a tablet, an emulsion, a solution, a drop pill, an injection, an aerosol, a gel, a patch, a drop, or a liniment.
9. The wound healing promoting medicament of claim 6, wherein the pharmaceutical indication comprises a diabetic wound or a non-diabetic wound.
10. The wound healing promoting medicament of claim 9, wherein the non-diabetic patient's wound comprises a burn, a scald, an ulcer, a dermatitis, a labor.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410306648.5A CN118161487A (en) | 2024-03-18 | 2024-03-18 | Application of benzisoxazole derivative in preparing wound healing promoting medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410306648.5A CN118161487A (en) | 2024-03-18 | 2024-03-18 | Application of benzisoxazole derivative in preparing wound healing promoting medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118161487A true CN118161487A (en) | 2024-06-11 |
Family
ID=91360150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410306648.5A Pending CN118161487A (en) | 2024-03-18 | 2024-03-18 | Application of benzisoxazole derivative in preparing wound healing promoting medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118161487A (en) |
-
2024
- 2024-03-18 CN CN202410306648.5A patent/CN118161487A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108586575B (en) | Polypeptide and application of polypeptide in skin repair function | |
| KR19990082523A (en) | Angiogenesis inhibitors | |
| CN108619086A (en) | A kind of Cellular gels preparation for treating tissue damage and application thereof and the active gel solution of holding freeze-stored cell used | |
| EP2145623A1 (en) | Pharmaceutical and cosmetic compositions for accelerated healing of wounds and other surface damages | |
| CN117357521A (en) | Application of azaindole compounds in preparation of wound healing promoting drugs | |
| CN117257808B (en) | Application of rutaecarpine in preparation of product for promoting wound healing | |
| CN117899072A (en) | Application of sodium ion channel inhibitor in preparation of medicine for promoting wound healing | |
| CN107158008B (en) | A kind of pharmaceutical composition for treating myocardial infarction | |
| EP0974352A1 (en) | Drugs inhibiting progress of pterygium and postoperative recurrence of the same | |
| CN118161487A (en) | Application of benzisoxazole derivative in preparing wound healing promoting medicine | |
| CN118161495A (en) | Application of quinoxaline derivative in preparing wound healing promoting medicine | |
| CN118161516A (en) | Application of oroxylin A-7 glucoside in preparation of wound healing promoting medicines | |
| CN118121578B (en) | Compound EH-P008V and application thereof in preparation of wound healing promoting drugs | |
| CN118161503A (en) | Application of small molecular compound BTZ043 in preparation of wound healing promoting medicine | |
| CN118161474A (en) | Application of N-benzamide compound in preparation of wound healing promoting medicine | |
| CN109010350B (en) | Application of pedunculoside in preparing medicine for treating diabetes skin ulcer | |
| CN118178418A (en) | Application of GPR119 agonist in preparation of wound healing promoting drugs | |
| CN118178407A (en) | Application of pan DUB enzyme inhibitor in preparation of wound healing promoting medicine | |
| CN118121595B (en) | Application of compound EH-P005J in preparation of wound healing promoting drugs | |
| CN118121594B (en) | Application of EH-P006N in preparation of medicine for promoting wound healing | |
| CN109134694B (en) | Sulfated derivative of dendrobium nobile polysaccharide and preparation method and application thereof | |
| CN118340765B (en) | Application of benzamide compound in preparation of wound healing promoting medicine | |
| CN111568937A (en) | Application of pien Tze Huang and preparation thereof in preparation of medicine for promoting healing of refractory wound | |
| CN118271276B (en) | Naphthalenone derivative for promoting wound healing as well as preparation method and application thereof | |
| CN118416058A (en) | Application of benzimidazole compound |
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 |