An mpo inhibitor, a method for preparing the same, and use thereof for preventing or treating hypertrophic scars and keloids

Abstract

The present invention provides a MPO inhibitor, a method of preparing the same and a new use in the manufacture of a medicament for preventing or treating hypertrophic scars and keloids.

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry, specifically relating to an MPO inhibitor, its preparation method, and its novel application in the preparation of drugs for the prevention or treatment of hypertrophic scars and keloids. Background Technology

[0002] Myeloperoxidase (MPO) is a heme-containing peroxidase primarily expressed and released in neutrophils. In the presence of hydrogen peroxide and halides, MPO catalyzes the production of highly oxidizing hypochlorous acid, playing a crucial role in neutrophil-mediated microbial killing. While the oxidants produced by peroxidases play a key role in microbial inactivation and virus killing, the excessive production of these active substances is associated with tissue damage. Increasing evidence suggests that the initiation and accumulation of peroxidase-mediated oxidative damage plays a significant role in the progression of various diseases.

[0003] For example, in heart disease, there is evidence that abnormal MPO synthesis not only exacerbates coronary atherosclerosis but also mediates post-ischemic ventricular remodeling and arrhythmias by increasing ventricular collagen deposition.

[0004] Secondly, studies have shown that the activity of peroxidase in the sputum of patients with cystic fibrosis is related to the severity of the disease, which supports the theory that MPO leads to progressive pulmonary dysfunction and chronic lung inflammation associated with cystic fibrosis.

[0005] Furthermore, MPO expression is increased in the brains of patients with Alzheimer's disease, Parkinson's disease, and multiple sclerosis. These data suggest that MPO may play an important role in the progression of neurodegenerative diseases.

[0006] Recent in vivo studies have shown that MPO levels and oxidative stress marker levels are elevated in colon cancer, lung cancer, and acute promyelocytic leukemia compared to normal tissues, supporting the hypothesis that MPO produced by activated neutrophils plays a role in carcinogenesis.

[0007] Although MPO has been shown to play a crucial role in various diseases, its potential therapeutic target for many diseases has not been effectively applied in clinical practice. Currently, the application of MPO inhibitors is still in the laboratory research stage and has not been widely adopted in clinical practice. Laboratory applications of MPO inhibitors mainly focus on the following aspects:

[0008] 1,2-Thiooxapurinol (AZM198): As an irreversible inhibitor of MPO, it inhibits the production of hypochlorous acid without releasing oxygen free radicals, thus suppressing oxidative stress. It has been reported to alleviate vascular inflammation and endothelial dysfunction in atherosclerotic mice, as well as liver damage in obese mice. Furthermore, AZM198 can reduce the morbidity and oxidative stress levels in mice with cystic fibrosis-like pneumonia.

[0009] 2. AZD5904: In recent years, AZD5904 has begun to be used in the laboratory to inhibit MPO activity. 1) It can improve the diastolic function defects of mast cardiomyocytes in mice. 2) It can improve sperm function. 3) It can reverse microvascular insulin resistance caused by a high-fat diet in mice.

[0010] MPO-IN-28: Although MPO-IN-28 is the first inhibitor to irreversibly inhibit MPO activity at extremely low concentrations (nanomolar) (IC50 = 44 nM), its application in the laboratory has not been reported.

[0011] Hypertrophic scars and keloids are mainly caused by excessive proliferation of fibroblasts, which secrete large amounts of collagen and extracellular matrix, accompanied by extensive angiogenesis and dilation, leading to hyperemia on the scar surface and further promoting scar tissue proliferation. Therefore, the key to scar treatment lies in inhibiting the proliferation of fibroblasts in scar tissue, reducing collagen fiber synthesis, promoting collagen fiber maturation, damaging the vascular intima, and occluding capillaries, thereby softening and shrinking the scar. In recent years, scar treatment methods have mainly included the following:

[0012] 1. After the deep burn wound has healed, pressure therapy can be used to apply pressure locally to close blood vessels, reduce the regeneration of microvessels, and inhibit the growth of fibroblasts.

[0013] 2. Topical silicones, Centella asiatica cream, and compound heparin sodium allantoin gel can inhibit fibroblast growth; topical corticosteroids can reduce inflammatory reactions within scars.

[0014] 3. It is recommended to wear various braces at an early stage to prevent scar adhesions and contracture deformities of the fingers, toes, face, neck, perineum, and joints.

[0015] 4. Early combined use of fractional carbon dioxide laser and pulsed dye laser can relieve scar congestion and reduce scar thickness.

[0016] 5. For particularly difficult-to-treat hypertrophic scars or keloids, radiation therapy may be considered.

[0017] 6. For contracture scars that affect function, especially deformities in important parts of a child's body, surgical methods should be considered first to restore normal function and ensure that normal growth and development are not affected, and then other treatment methods should be used in conjunction.

[0018] Although various methods exist for treating scars in clinical practice, the results remain limited. The drawbacks are:

[0019] 1. Combining multiple methods makes the treatment process cumbersome;

[0020] 2. The treatment cycle is long, and patient compliance is poor;

[0021] 3. The treatment is slow, making it difficult for patients to adhere to the regimen;

[0022] 4. High treatment costs;

[0023] 5. Lack of targeted treatment for scars, resulting in insufficient precision in treatment.

[0024] Targeted therapy involves designing drugs to specifically bind to a identified pathogenic protein molecule or gene fragment to exert a therapeutic effect. Its effectiveness and precision have been demonstrated in cancer treatment. Scar formation also involves alterations in various genes and protein molecules; whether targeted therapy can be implemented is worth exploring. Scar formation involves many signaling molecules between cells and extracellular mechanisms. Intervention targeting cytokines and genes may achieve the goal of preventing and treating scars. TGF-β1 is currently the cytokine most closely related to scar formation. It can regulate wound healing and scar formation through the TGF-β1 / Smad signaling pathway. While topical application of recombinant human TGF-β3 (proposed brand name Juvista) showed good results in phase I and II clinical trials, it was ineffective in phase III clinical trials.

[0025] Therefore, there is an urgent need to find new targets for scar treatment. Summary of the Invention

[0026] The problem the invention aims to solve:

[0027] The purpose of this invention is to provide an MPO inhibitor, its preparation method, and its novel application in the preparation of medicaments for the prevention or treatment of hypertrophic scars and keloids.

[0028] Solution methods:

[0029] To address the aforementioned technical problems, in a first aspect, the present invention provides an MPO inhibitor or a pharmaceutically acceptable salt thereof conforming to the following chemical structural formula Ia:

[0030]

[0031] in,

[0032] R1 is selected from H, C1-C4 alkyl, C3-C8 cycloalkyl, or C3-C8 heterocycloalkyl;

[0033] R2 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, or C3-C8 heterocycloalkyl.

[0034] Preferably, R1 is methyl and R2 is methoxy.

[0035] Preferably, the MPO inhibitor or a pharmaceutically acceptable salt thereof is a compound with the following chemical structural formula I:

[0036]

[0037] Secondly, the present invention also provides a method for preparing the MPO inhibitor as described above or a pharmaceutically acceptable salt thereof, the synthesis method being as follows:

[0038]

[0039] Thirdly, the present invention also provides the use of the MPO inhibitor as described above or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the prevention or treatment of hypertrophic scars and keloids.

[0040] Preferably, this includes administering a therapeutically effective amount of an MPO inhibitor to the patient.

[0041] Fourthly, the present invention also provides a pharmaceutical composition for the prevention or treatment of hypertrophic scars and keloids, comprising an MPO inhibitor as described above or a pharmaceutically acceptable salt thereof.

[0042] The pharmaceutical composition is administered to patients with hypertrophic scars via oral, parenteral, transdermal, topical, rectal, or nasal routes, and is expected to deliver an effective dose to patients with hypertrophic scars.

[0043] Fifthly, the present invention also provides a pharmaceutical kit for the prevention or treatment of hypertrophic scars and keloids, comprising an MPO inhibitor as described above or a pharmaceutically acceptable salt thereof. Attached Figure Description

[0044] Figure 1 The expression levels of the MPO inhibitor or GAPDH internal control antibody of the present invention in scar fibroblasts (HSF) and normal tissue fibroblasts (HFB) were detected by Western blot.

[0045] Figure 2 The collagen secretion status was observed 24 hours after treatment with scar fibroblasts (HSF) using the MPO inhibitor, GAPDH internal reference antibody, or two other collagens of the present invention.

[0046] Figure 3 Photos of rabbit ear hypertrophic scars before and after injection of the MPO-IN-28 of this invention. Detailed Implementation

[0047] The present invention will be further described below with reference to the accompanying drawings and the following embodiments. It should be understood that the drawings and the following embodiments are for illustrative purposes only and are not intended to limit the present invention. The same or corresponding reference numerals in the drawings denote the same parts, and repeated descriptions are omitted.

[0048] This invention provides an MPO inhibitor of general chemical formula Ia or a pharmaceutically acceptable salt thereof:

[0049]

[0050] in,

[0051] R1 is selected from H, C1-C4 alkyl, C3-C8 cycloalkyl, or C3-C8 heterocycloalkyl;

[0052] R2 is selected from H, C1-C4 alkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, or C3-C8 heterocycloalkyl.

[0053] Preferably, R1 is methyl and R2 is methoxy.

[0054] Preferably, the MPO inhibitor or a pharmaceutically acceptable salt thereof is a compound with the following chemical structural formula I:

[0055]

[0056] This invention uses a compound of chemical structural formula I as an example of an MPO inhibitor, and refers to it as the MPO-IN-28 inhibitor.

[0057] In a preferred embodiment of the present invention, the compound of general chemical formula I provided by the present invention can be synthesized by the following synthetic scheme:

[0058]

[0059] Unless otherwise stated, the groups and terms used in the above synthetic schemes have the same meanings as those used in compounds of general formula I.

[0060] The above synthesis schemes only illustrate some of the preparation methods of the compounds in this invention. Based on the above synthesis schemes, those skilled in the art can use similar methods to synthesize the compounds of this invention, referring to commonly used techniques and existing technologies in the field.

[0061] Previously, it was believed that MPO could only exert its effects through release into tissues via neutrophils. However, the inventors of this invention discovered that MPO is highly expressed in fibroblasts of hypertrophic scar tissue compared to normal skin tissue. Furthermore, the application of MPO inhibitors significantly reduced the expression of type 1 and 3 collagen and α-SMA in fibroblasts. This finding suggests that high MPO expression in fibroblasts may promote fibroblast proliferation and differentiation, stimulate collagen secretion, and promote hypertrophic scars and keloids. MPO may become a key target for the clinical treatment of hypertrophic scars, providing a new target for precision scar treatment. Therefore, MPO inhibitors can be used to prevent or treat hypertrophic scars and keloids, and can be prepared as pharmaceutical compositions or kits for administration to patients with hypertrophic scars and keloids. In cell experiments, MPO-IN-28 induced apoptosis in half of the fibroblasts at 17 μmol / L. In animal experiments, 2.52 mol / kg MPO-IN-28 caused acute poisoning in half of the mice. Since it has not yet been tested and applied in clinical practice, the safe and effective concentrations for patients are still unknown.

[0062] MPO inhibitor compounds of formula Ia, or pharmaceutically acceptable salts thereof, can be administered to patients with hypertrophic scars and keloids in effective doses. The compounds can be administered to patients with hypertrophic scars and keloids via an oral, parenteral, transdermal, topical, rectal, or nasal route through a pharmaceutical composition. It should be understood that appropriate carriers and excipients can be selected according to the route of administration of the pharmaceutical composition.

[0063] The "compounds" described in this invention include all stereoisomers, geometric isomers, tautomers, and isotopes.

[0064] The "compound" described in this invention may be asymmetric, for example, having one or more stereoisomers. Unless otherwise stated, all stereoisomers include, for example, enantiomers and diastereomers. Compounds containing asymmetric carbon atoms in this invention may be isolated in optically active pure form or in racemic form; the optically active pure form may be resolved from racemic mixtures or synthesized using chiral starting materials or chiral reagents.

[0065] The "compound" described in this invention also includes a tautomer form; the tautomer form is derived from the exchange of a single bond with an adjacent double bond and the migration of a proton.

[0066] This invention also includes atoms of all isotopes, whether in intermediates or the final compound; isotopic atoms include those having the same number of atoms but different mass numbers, for example, hydrogen isotopes include deuterium and tritium. Furthermore, if desired, for example for specific therapeutic or diagnostic purposes, the compounds of this invention may incorporate isotopes or radioactive isotopes known in the art, such as… 3 H, 15 O、 13 C or 13 Nitrogen isotopes.

[0067] "Pharmaceutically acceptable salts" refer to salts that are pharmaceutically acceptable and possess the pharmacological activity of their parent compounds. These salts include:

[0068] (1) When an acidic proton is sought in the parent compound, it may be replaced by a suitable metal ion, such as an alkali metal ion; or it may be combined with ammonia or an organic base, such as a natural or non-natural amino acid, L-lysine, L-arginine, L-serine, L-glutamic acid, ethanolamine, diethanolamine, triethanolamine, tromethamine, an amino sugar, N-methylglucosamine (glucosamine), or an analogue to form a salt. This salt formation may require a monobasic salt, such as a salt with a single acidic group, or it may require a dibasic salt, such as a salt with two acidic groups. This salt may contain a certain amount exceeding the required quantity of an inorganic or organic base calculated according to the number of acidic groups contained in the compound of the present invention, for example, to adjust the pH of the solution or to enhance the storage stability of the salt; or

[0069] (2) Acid addition salts that form with inorganic acids including hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or similar acids; and with organic acids including acetic acid, propionic acid, hexanoic acid, cyclopentylpropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, mandelic acid, methanesulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, salicylic acid, stearic acid, mucoconic acid, or similar substances.

[0070] The compounds according to the present invention can also exist in their solvated forms, such as hydrates (hemihydrates, monohydrates, dihydrates, trihydrates, etc.).

[0071] In this invention, unless otherwise specified, the terms used have the following meanings.

[0072] The term "alkyl" refers to a straight-chain or branched saturated aliphatic hydrocarbon group consisting of carbon and hydrogen atoms, and is a straight-chain or branched alkyl group containing 1 to 20 carbon atoms (C1-C2). 20Alkyl groups, preferably C1-C8 alkyl groups, more preferably C1-C6 alkyl groups, and even more preferably C1-C4 haloalkyl groups, such as methyl, ethyl, propyl (including n-propyl and isopropyl), butyl (including n-butyl, isobutyl, sec-butyl or tert-butyl), pentyl (including n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl), and hexyl (n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl). The alkyl group may be unsubstituted or substituted with one or more substituents, including but not limited to alkyl groups and halogens, such as 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, etc.; the alkyl group may be unsubstituted or substituted with one or more substituents, the substituents including but not limited to alkyl groups and halogens, for example forming haloalkyl groups, preferably C1-C8 haloalkyl groups, more preferably C1-C6 haloalkyl groups, and even more preferably C1-C4 haloalkyl groups.

[0073] The term "cycloalkyl" refers to a cyclic hydrocarbon substituent of a saturated or partially unsaturated monocyclic or polycyclic (fused, spiro, or bridged) ring containing 3 to 8 carbon atoms, preferably 3 to 6 carbon atoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, spiro[3.4]octyl, bicyclo[3.1.1]hexyl, etc. The cycloalkyl group may be unsubstituted or substituted with one or more substituents, including but not limited to alkyl, halogen, sulfonyl, sulfinyl, for example, forming a halocycloalkyl group, preferably a C3-C8 halocycloalkyl group, more preferably a C3-C6 halocycloalkyl group.

[0074] The term "heterocyclic alkyl" refers to a monocyclic or polycyclic (fused, spiro, or bridged) cyclic hydrocarbon substituent that is saturated or partially unsaturated and contains one or more heteroatoms of N, O, or S. Heterocyclic alkyl groups contain 3 to 8 ring atoms, of which 1 to 3 are heteroatoms; preferably, they contain 3 to 6 ring atoms, of which 1 to 2 are heteroatoms. Typically, they are 3- to 6-membered heterocyclic groups containing one or more heteroatoms of N, O, or S, such as azirropropane-1-yl, oxacyclobutane-3-yl, azirrobutane-3-yl, azirrobutane-1-yl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazineyl, tetrahydropyranyl, tetrahydrothiopyranyl, dioxotetrahydrothiopyranyl, morpholinyl, and their derivatives. The heterocyclic alkyl group may be unsubstituted or substituted with one or more substituents, including but not limited to alkyl, halogen, sulfonyl, sulfinyl, and oxo groups, for example forming a haloheterocyclic alkyl group, preferably a haloheterocyclic alkyl group containing 3-8 ring atoms.

[0075] Administration and pharmaceutical compositions

[0076] The term "pharmaceutical composition" as used in this invention refers to a formulation comprising one or more compounds of the invention or salts thereof, and a carrier commonly accepted in the art for delivering a bioactive compound to an organism (e.g., a human). The purpose of the pharmaceutical composition is to facilitate drug delivery to the organism.

[0077] The term "pharmaceutically acceptable carrier" refers to a substance that is co-administered with the active ingredient and facilitates the administration of the active ingredient. This includes, but is not limited to, any flow aids, sweeteners, diluents, preservatives, dyes / colorants, flavor enhancers, surfactants, wetting agents, dispersants, disintegrants, suspending agents, stabilizers, isotonic agents, solvents, or emulsifiers that are permitted by the State Food and Drug Administration for use in humans or animals (e.g., livestock). Examples include, but are not limited to, calcium carbonate, calcium phosphate, various sugars and starches, cellulose derivatives, gelatin, vegetable oils, and polyethylene glycol.

[0078] The pharmaceutical compositions described in this invention can be formulated into solid, semi-solid, liquid, or gaseous preparations, such as tablets, pills, capsules, powders, granules, ointments, emulsions, suspensions, solutions, suppositories, injections, inhalers, gels, microspheres, and aerosols, etc.

[0079] The pharmaceutical composition described in this invention can be manufactured using methods well known in the art, such as conventional mixing, dissolving, granulation, sugar-coated pill making, grinding, emulsification, freeze drying, etc.

[0080] The routes of administration for the compounds or pharmaceutically acceptable salts thereof or pharmaceutical compositions described in this invention include, but are not limited to, oral, rectal, transmucosal, enteral administration, or local, transdermal, inhalation, parenteral, sublingual, intravaginal, intranasal, intraocular, intraperitoneal, intramuscular, subcutaneous, and intravenous administration. Transdermal administration is a preferred route of administration.

[0081] For oral administration, the pharmaceutical composition can be formulated by mixing the active compound with a pharmaceutically acceptable carrier well known in the art. These carriers enable the compounds of the present invention to be formulated into tablets, pills, lozenges, sugar-coated tablets, capsules, liquids, gels, pastes, suspensions, etc., for oral administration to patients. For example, a pharmaceutical composition for oral administration can be obtained as a tablet by combining the active ingredient with one or more solid carriers, granulating the resulting mixture if necessary, and adding a small amount of excipients to process it into a mixture or granules to form a tablet or tablet core. The tablet core can be combined with a coating material optionally suitable for enteric coating to process it into a coated formulation more favorable for absorption by the organism (e.g., human).

[0082] “Treatment” means any treatment of disease in a mammal, including: (1) preventing disease, i.e. causing the symptoms of clinical disease to not develop; (2) suppressing disease, i.e. preventing the development of clinical symptoms; and (3) alleviating disease, i.e. causing the clinical symptoms to subside.

[0083] The present invention will be further described in detail below with reference to specific embodiments. It should also be understood that the following embodiments are only for further illustration of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above description of the present invention are within the scope of protection of the present invention. The specific process parameters, etc., in the following examples are merely examples within a suitable range; that is, those skilled in the art can make appropriate selections within the appropriate range based on the description herein, and are not intended to be limited to the specific values ​​in the examples below.

[0084] Specific embodiments of the invention are described in detail in the following examples. These are illustrative of the invention and not intended to limit its scope. Common abbreviations familiar to those skilled in the art are used. All reagents were commercially available or prepared using conventional methods described in existing literature.

[0085] Example:

[0086] Cellular experiments:

[0087] 1. Extraction of fibroblasts from scar tissue and normal skin tissue:

[0088] Primary fibroblasts were extracted from scar tissue and normal skin tissue of clinical patients in the proliferative phase using the tissue block culture method. Tissue obtained during surgery was cut into 1cm pieces, and an appropriate amount of complete culture medium was added to each piece, just enough to submerge it. The frequency of moving the culture flask was minimized to avoid excessive shaking that could cause the tissue blocks to detach from the culture vessel. To facilitate cell adhesion, the medium was not changed for the first 3 days. Once the cell density reached 80%, the cells were digested with 0.25% trypsin and passaged. After three passages of purification, the cells were used for subsequent experiments.

[0089] 2. Differential expression of MPO in fibroblasts (HSF) in scar tissue and fibroblasts (HFB) in normal tissue:

[0090] Figure 1 The expression levels of the MPO inhibitor or GAPDH internal control antibody of the present invention in scar fibroblasts (HSF) and normal tissue fibroblasts (HFB) were detected by Western blot.

[0091] from Figure 1 It can be seen that, according to the MPO expression levels in HSF and HFB detected by Western blot, the MPO expression in HSF is significantly increased.

[0092] 3. Effects of MPO inhibitor (MPO-IN-28) on HSF:

[0093] Figure 2 The collagen secretion status was observed 24 hours after treatment with scar fibroblasts (HSF) using the MPO inhibitor, GAPDH internal reference antibody, or two other collagens of the present invention.

[0094] from Figure 2 It can be seen that after treating HSF with the MPO inhibitor MPO-IN-28 (2 μmol / l) for 24 hours, collagen secretion decreased significantly.

[0095] Animal experiments:

[0096] 1. Establishing a rabbit ear hypertrophic scar model: After intravenous anesthesia of the rabbit ear margin, a 1cm diameter circular wound was made on the ventral side of the rabbit ear using a trephine. The perichondrium was removed, the cartilage was dissected, and major blood vessels were avoided. Four wounds were made on each ear. After achieving adequate hemostasis, the wounds were covered with sterile dressings. Photos were taken every two days for record-keeping.

[0097] 2. MPO-IN-28 injection: 25 days after surgery, when the wound was completely epithelialized, the four wounds of each rabbit ear were divided into an experimental group and a control group. The experimental group was injected with 200ul of 20mmol / l MPO-IN-28 along the base of the scar, while the control group was injected with the same dose of PBS.

[0098] 3. 45 days post-surgery, photographs were taken to record the differences in rabbit ear scars, and scar specimens were taken for histological examination.

[0099] Figure 3 Photos of rabbit ear hypertrophic scars before and after injection of the MPO-IN-28 of this invention. From Figure 3 It can be seen that MPO-IN-28 significantly improves proliferative scarring in rabbit ears.

[0100] The above experimental results demonstrate that MPO-IN-28 can significantly inhibit the function of fibroblasts in scars and improve scar hyperplasia in rabbit ears, which may provide a new direction for clinical scar treatment.

[0101] The above detailed embodiments further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above are merely one specific embodiment of the present invention and are not limited to the scope of protection of the present invention. The present invention can be embodied in various forms without departing from its essential characteristics. Therefore, the embodiments described herein are for illustrative purposes only and not for limitation. Since the scope of the present invention is defined by the claims rather than the specification, all changes falling within the scope defined by the claims, or their equivalents, should be understood to be included in the claims. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. Use of an MPO inhibitor or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the prevention or treatment of hypertrophic scars and keloids, said MPO inhibitor conforming to the following chemical structural formula Ia: ， in, R1 is methyl, and R2 is methoxy.

2. The application according to claim 1, characterized in that, This includes administering a therapeutically effective dose of an MPO inhibitor to the patient.

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