CN117442610A - Application of compound 8519-0065 in preparation of medicine for promoting skin wound healing - Google Patents
Application of compound 8519-0065 in preparation of medicine for promoting skin wound healing Download PDFInfo
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- CN117442610A CN117442610A CN202311528316.3A CN202311528316A CN117442610A CN 117442610 A CN117442610 A CN 117442610A CN 202311528316 A CN202311528316 A CN 202311528316A CN 117442610 A CN117442610 A CN 117442610A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 53
- 206010072170 Skin wound Diseases 0.000 title claims abstract description 30
- 230000029663 wound healing Effects 0.000 title claims abstract description 20
- 239000003814 drug Substances 0.000 title claims abstract description 19
- 230000001737 promoting effect Effects 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims description 9
- 230000035876 healing Effects 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 150000003384 small molecules Chemical class 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 238000002347 injection Methods 0.000 claims description 11
- 239000007924 injection Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 229920002253 Tannate Polymers 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 229940077388 benzenesulfonate Drugs 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229940049920 malate Drugs 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 239000007972 injectable composition Substances 0.000 claims 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 8
- 230000005012 migration Effects 0.000 abstract description 6
- 238000013508 migration Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 206010052428 Wound Diseases 0.000 description 24
- 208000027418 Wounds and injury Diseases 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 210000003491 skin Anatomy 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000009592 kidney function test Methods 0.000 description 3
- 238000007449 liver function test Methods 0.000 description 3
- 208000032544 Cicatrix Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000002847 Surgical Wound Diseases 0.000 description 2
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 230000037387 scars Effects 0.000 description 2
- -1 small molecule compounds Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000009168 stem cell therapy Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010043275 Teratogenicity Diseases 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 230000036074 healthy skin Effects 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000029774 keratinocyte migration Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic 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)
- 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 an application of a compound 8519-0065 in preparing a medicament for promoting skin wound healing, wherein the molecular formula of the compound 8519-0065 is C 26 H 25 N 5 O 2 S, the structural formula isThe invention provides a medicine for promoting the healing of skin wound surface by using the compound 8519-0065, in particular a small molecule medicine which takes the compound 8519-0065 or pharmaceutically acceptable salt thereof as an active ingredient, achieves the effect of promoting the healing of skin wound surface by promoting the migration of epidermal keratinocytes, has high safety and stable medicine, can treat large-area skin wound surface, has low synthesis cost, provides a new way for clinically treating the skin wound surface healing, and has important clinical application value.
Description
Technical Field
The invention belongs to the field of biological medicine, and in particular relates to application of a compound 8519-0065 in preparing a medicine for promoting skin wound healing.
Background
Trauma, the first disease of global morbidity and teratogenicity, accounts for 12% of all diseases. Among the lesions caused by wounds, skin wounds are the most common, with new cases over ten million per year. When the skin defect is too large, the wound infection is serious or the basic condition of the patient is poor, the wound is difficult to heal, and the living quality of the individual patient and the national medical expense are greatly influenced. In the united states alone, refractory wounds require approximately $ 500 million healthcare costs per year, with surgical incisions and wounds resulting in refractory wounds of approximately $ 120 hundred million and burns resulting in refractory wounds of approximately $ 75. However, no ideal treatment method is available at present to effectively promote the healing of skin wound surfaces.
The current methods for promoting the healing of skin wound surfaces have various but obvious limitations, and the main methods are as follows:
1. wound surface covering wet dressing: only provides a closed wet environment for the wound surface, is beneficial to wound surface healing, but cannot directly activate the proliferation, migration and other capacities of wound surface cells to accelerate the healing process, and has limited effect.
2. Negative pressure sealing drainage: the method indirectly provides good environment for wound healing, but does not directly promote wound growth, has limited clinical curative effect and inaccurate treatment target spot.
3. Growth factors/cytokines: can promote granulation tissue proliferation to a certain extent, thereby accelerating wound healing, but the growth factors/cytokines belong to biological products, are easy to generate safety problems such as allergy and the like, have unstable activity, are easy to inactivate and limit clinical application.
4. Surgical treatment: skin grafting/skin flap grafting is carried out by cutting off the wound surface, and cutting healthy skin from other parts of the patient to cover the wound surface, so that the treatment process of the method is very painful, can cause damage to the skin supply area and leave large-area scars, and cannot be suitable for patients with large-area skin wound surfaces.
5. Cell therapy: is an emerging treatment technology, but has the risk of generating tumors and poor safety.
In conclusion, the common methods such as wet dressing and negative pressure closed drainage all indirectly promote the healing by providing good environment for the wound healing, but can not directly promote the wound growth, and the growth factors, cytokines, stem cell therapies and the like are all biological products, have poor safety and stability, have higher preparation cost and limit the clinical application of the biological products. Thus, there is currently a lack of convenient and effective methods for promoting healing of skin wounds.
Compounds 8519-0065 are small molecule compounds of the formula C from the Chemdiv library (https:// www.chemdiv.com) 26 H 25 N 5 O 2 S has a molecular weight of 471.58, a structural formula shown in figure 1, is a lipophilic molecule, has low solubility in water, and has no related research and application report on pharmacological activity of the compound 8519-0065 at present.
Disclosure of Invention
In order to solve the problems that the conventional wet dressing and negative pressure closed drainage methods at present cannot directly promote wound surface growth and biological products such as growth factors, cytokines, stem cell therapies and the like are poor in safety and stability, the invention aims to provide the application of the compounds 8519-0065 in preparing medicines for promoting skin wound surface healing, and the application of the compounds 8519-0065 in preparing medicines for promoting skin wound surface healing is characterized in that the Chemdiv compound library is subjected to high-throughput screening, so that the micromolecular compounds 8519-0065 can effectively promote the migration of epidermal keratinocytes, thereby promoting skin wound surface healing.
The above object of the present invention is achieved by the following technical solutions:
the invention provides application of a compound 8519-0065 or pharmaceutically acceptable salt thereof in preparing medicaments for promoting skin wound healing, wherein the molecular formula of the compound 8519-0065 is C 26 H 25 N 5 O 2 S has a molecular weight of 471.58 and a structural formula of
Preferably, the promotion of skin wound healing means that the formed skin wound is completely healed or the area of the skin wound is reduced.
Preferably, the pharmaceutically acceptable salt of the compound 8519-0065 is selected from one or more of hydrochloride, hydrobromide, sulfate, acetate, lactate, tartrate, tannate, citrate, trifluoroacetate, malate, maleate, succinate, p-toluenesulfonic acid or benzenesulfonate.
The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of compounds 8519-0065 and/or a pharmaceutically acceptable salt thereof, wherein compounds 8519-0065 have the formula C 26 H 25 N 5 O 2 S, the structural formula is
Preferably, the concentration of the compound 8519-0065 in the pharmaceutical composition is 1-100. Mu.M.
More preferably, the concentration of the compound 8519-0065 in the pharmaceutical composition is 5-50. Mu.M.
Preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient, and can be prepared into injection, emulsion, tablet, powder, granule, ointment, liposome or oral liquid.
The invention also provides a small molecule injection preparation, which comprises a therapeutically effective amount of the compound 8519-0065 and/or pharmaceutically acceptable salt thereof, wherein the molecular formula of the compound 8519-0065 is C 26 H 25 N 5 O 2 S, the structural formula is
Preferably, the compounds 8519-0065 and/or pharmaceutically acceptable salts thereof are used as active ingredients in a concentration of 1-100. Mu.M.
The invention provides application of a compound 8519-0065 in preparing a medicament for promoting skin wound healing, in particular a small molecule medicament taking the compound 8519-0065 as an active ingredient. Compared with the prior art, the invention has the beneficial effects that:
(1) The compounds 8519-0065 promote the migration of epidermal keratinocytes, thereby achieving the effect of promoting the healing of skin wound surfaces.
(2) Compared with stem cells, the small molecular medicine has high treatment safety and stable medicine, so that the defects of poor safety, possibility of tumor generation and the like are avoided; compared with the operation treatment, the external preparation can treat a large-area skin wound surface, and avoid the defects of small treatment range, damage to the skin supply area and leaving large-area scars; compared with the wound surface covering wet dressing and negative pressure closed drainage, the method avoids the defects of no definite treatment target point, low efficiency, poor effectiveness and the like; compared with growth factors/cytokines, the method avoids the defects of easy allergy generation, poor safety of biological products, unstable activity, easy inactivation and the like; compared with the existing medicines, the preparation method has obvious advantages in cost and low synthesis cost.
Drawings
FIG. 1 is a molecular structure of compounds 8519-0065.
FIG. 2 is a graph showing the cell migration ability of the post-scratch treatment compound 8519-0065 of the human epidermal keratinocyte line (HaCaT) in the examples.
FIG. 3 is a graph showing the wound healing results of the skin wound healing model promoted by the compounds 8519-0065 in the examples.
FIG. 4 shows the results of cytotoxicity test (MTT assay) of the compounds 8519-0065 in examples.
FIG. 5 shows the results of liver and kidney function test of mice by subcutaneous injection of the compound 8519-0065.
Detailed Description
The invention is further illustrated by the following examples:
example 1
1. Material
Molecular physicochemical Properties of Compounds 8519-0065: compounds 8519-0065 (CAS number 1010868-12-8) were purchased from Shanghai Siderurgica biological medicine Co., ltd., chemical formula C 26 H 25 N 5 O 2 S, the molecular weight is 471.58, the structural formula is shown in figure 1, and after the injection into wound surface edge tissues, the injection is not easy to be absorbed and diffused into capillary vessels to enter body circulation by hydrophilic tissues due to good fat solubility, so that the effect of local action can be achieved, and the injection can not act on tissues and organs except skin wound surface tissues.
2. Experimental method
2.1 cell migration Capacity test (cell scratch test)
Human epidermal keratinocyte cell line (HaCaT) was seeded in six-well plates and when cells were grown to full six-well plates, scratches were formed with micropipette tips. After the scratch, haCaT cells were treated with 5, 20 μm of the compound 8519-0065 or the control solvent for 24 hours, respectively, and the decrease in the distance between cells on both sides of the scratch was observed, and the distance between cells on both sides of the scratch was measured using Image J software.
2.2 establishment of wound healing model of mice
The wound healing model is described in the prior art (The mouse excisional wound splinting model, including applications for stem cell transformation. Nature protocol.2013;8 (2): 302-9.). Briefly, C57/BL6 mice of 12 weeks old were anesthetized, back skin was prepared, a full-layer excision wound surface of skin with a diameter of 8 mm was made at the back midline position, and a meat membrane was cut off, a ring of a silicone annular splint was fixed on the skin around the wound surface by sewing with 4-0 silk threads, to prevent the skin from shrinking to cause the wound surface to be closed, and the mice were photographed immediately after the operation, on days 7 and 14, and the wound surface area was counted using Image J.
2.3 injection of Compound 8519-0065
On the day when the establishment of the small wound healing model begins, the injection of the compound 8519-0065 is started and is injected subcutaneously around the wound. The mice were randomly divided into two groups, a control group (solvent group) and an experimental group (compound 8519-0065 administration group). Each group had 6 mice. The preparation method comprises injecting once every other day, injecting medicine or control solvent 10 μl at 8 points around each wound surface, and injecting with 34-gauge needle (World Precision Instruments, saraota, FL) connected with 10 μl NanoFil microinjector (World Precision Instruments) until the materials are obtained, wherein the concentration of the compound 8519-0065 in the injection is 50 μM.
3. Experimental results
3.1 Compounds 8519-0065 promote epidermal keratinocyte migration
The migration ability of the small molecule compounds 8519-0065 treated after scratching of the human epidermal keratinocyte line (HaCaT) is shown in FIG. 2, and it can be seen that the migration ability of the cells treated with the compounds 8519-0065 is significantly higher than that of the control group (P < 0.001).
3.2 Compounds 8519-0065 promote healing of skin wounds
The wound healing conditions of different groups of mice recorded by photographing on days 0, 7 and 14 after the wound healing model is established show that the wound areas of mice of the treatment group injected with the compounds 8519-0065 are obviously reduced (P < 0.001) in days 7 and 14 compared with the control group (figure 3).
Example 2
1) Drug cytotoxicity test (MTT experiment)
Human epidermal keratinocyte cell line (HaCaT) was seeded in six well plates and 10. Mu.L of MTT solution (5 mg/mL) was added to each well after incubation of cells with different concentrations (1-50. Mu.M) of 8519-0065 or control solvent, respectively, for 24 hours. Incubation was continued for 4 hours, the culture was terminated, 100. Mu.L of DMSO was added to each well, the crystals were allowed to fully dissolve, the wavelength of 490nm was selected, and the light absorption value of each well was measured on an microplate reader.
The results of the human epidermal keratinocyte cell line (HaCaT) MTT assay are shown in FIG. 4, which shows that treatment with different concentrations of 8519-0065 (1-50. Mu.M) has no significant toxicity to epidermal keratinocytes.
2) Liver and kidney function test of mice
The main indexes of liver and kidney functions are detected by using an ALT detection kit (Abcam company, cat# ab 285263), an AST detection kit (Abcam company, cat# ab 263882), a creatinine detection kit (enzyme-linked organism, cat# ml 037726) and a urea nitrogen detection kit (enzyme-linked organism, cat# ml 076478) after 14 days after the wound healing molding mice are molded (namely, 14 days after injection).
The results of liver function test (ALT, AST) and kidney function test (creatinine, urea nitrogen) of mice are shown in FIG. 5, which shows that the subcutaneous injection of 50 mu M compound 8519-0065 has no obvious effect on liver and kidney functions of mice.
The foregoing is a preferred embodiment of the present invention, but the present invention should not be limited to the disclosure of this embodiment. So that equivalents and modifications will fall within the scope of the invention, all within the spirit and scope of the invention as disclosed.
Claims (9)
1. Use of compound 8519-0065 or pharmaceutically acceptable salt thereof in preparation of medicament for promoting skin wound healing, wherein molecular formula of compound 8519-0065 is C 26 H 25 N 5 O 2 S, the structural formula is
2. The use according to claim 1, wherein the promotion of skin wound healing means complete healing of the skin wound that has been formed or reduction of the area of the skin wound.
3. The use according to claim 1, wherein the pharmaceutically acceptable salt of the compound 8519-0065 is selected from one or more of the group consisting of hydrochloride, hydrobromide, sulfate, acetate, lactate, tartrate, tannate, citrate, trifluoroacetate, malate, maleate, succinate, p-toluene sulfonic acid or benzenesulfonate.
4. A pharmaceutical composition comprising a therapeutically effective amount of compounds 8519-0065 and/or a pharmaceutically acceptable salt thereof, wherein compounds 8519-0065 have the formula C 26 H 25 N 5 O 2 S, the structural formula is
5. The pharmaceutical composition according to claim 4, wherein the concentration of the compound 8519-0065 in the pharmaceutical composition is 1-100 μm.
6. The pharmaceutical composition according to claim 5, wherein the concentration of the compound 8519-0065 in the pharmaceutical composition is 5-50 μm.
7. The pharmaceutical composition of claim 4, further comprising a pharmaceutically acceptable carrier or excipient, and wherein the pharmaceutical composition is formulated as an injection, emulsion, tablet, powder, granule, ointment, liposome, or oral liquid.
8. A small molecule injectable formulation comprising a therapeutically effective amount of compounds 8519-0065 and/or a pharmaceutically acceptable salt thereof, wherein compounds 8519-0065 have the formula C 26 H 25 N 5 O 2 S, the structural formula is
9. The small molecule injection preparation according to claim 8, wherein the compound 8519-0065 and/or a pharmaceutically acceptable salt thereof is used as an active ingredient at a concentration of 1-100 μm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311528316.3A CN117442610A (en) | 2023-11-16 | 2023-11-16 | Application of compound 8519-0065 in preparation of medicine for promoting skin wound healing |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311528316.3A CN117442610A (en) | 2023-11-16 | 2023-11-16 | Application of compound 8519-0065 in preparation of medicine for promoting skin wound healing |
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| Publication Number | Publication Date |
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| CN117442610A true CN117442610A (en) | 2024-01-26 |
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|---|---|---|---|
| CN202311528316.3A Pending CN117442610A (en) | 2023-11-16 | 2023-11-16 | Application of compound 8519-0065 in preparation of medicine for promoting skin wound healing |
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| Country | Link |
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| CN (1) | CN117442610A (en) |
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- 2023-11-16 CN CN202311528316.3A patent/CN117442610A/en active Pending
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