Method and use of compound for treating diseases

Abstract

Provided in the present application is a method for preventing or treating acute bacterial skin and skin structure infections (ABSSSI), or alleviating ABSSSI-related conditions. The method comprises administering a therapeutic agent by intravenous infusion to a patient in need thereof for up to 7 consecutive days, wherein the therapeutic agent for each intravenous infusion comprises about 10 mg to about 500 mg of a compound as shown in formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance thereof.

Description

Methods and uses of compounds for treating diseases Technical Field

[0001] The present invention relates to the field of biomedicine, and more particularly to a method for preventing or treating a disease using a compound and its use. Background Art

[0002] Acute bacterial skin and skin structure infections (ABSSSIs) are the most commonly diagnosed skin infections worldwide and include cellulitis, wound infections, and severe skin abscesses, including Fournier's gangrene. The prevalence of ABSSSIs and the demand for treatment options are currently on the rise. On the one hand, the increasing resistance of pathogenic bacteria to antibiotics has made empirical antibiotic treatment increasingly difficult, and the diverse clinical landscape of the disease has made it difficult for physicians and treatment institutions to select the most appropriate treatment. On the other hand, extensive clinical data from practical experience demonstrate that a significant proportion of patients who receive inappropriate antibiotic treatment are significantly more likely to experience prolonged hospitalization and increased risk of morbidity and mortality. Furthermore, the high frequency of comorbidities (such as diabetes or obesity) that often accompany ABSSSIs complicate the selection of appropriate antibiotics.

[0003] Summary of the Invention

[0004] The purpose of the present invention is to provide a more effective treatment method, which can cure or alleviate ABSSSI-related disease symptoms in patients with short-term antibacterial treatment.

[0005] In one aspect, the present application provides a method for preventing or treating acute bacterial skin and skin structure infections (ABSSSI), or alleviating symptoms associated with the ABSSSI, comprising administering a therapeutic agent intravenously to a patient in need thereof for up to 7 days, wherein each intravenous infusion of the therapeutic agent comprises about 10 mg to about 500 mg of a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite, or deuterated form thereof.

[0006] In some embodiments, the method comprises administering the therapeutic agent intravenously to the patient in need thereof at intervals of about 8 hours to about 24 hours.

[0007] In some embodiments, the method comprises administering the therapeutic agent to the patient in need thereof at intervals of about 12 hours via intravenous infusion.

[0008] In some embodiments, the intravenous infusion is administered over a bolus period of about 20 minutes to about 3 hours.

[0009] In some embodiments, the intravenous infusion is administered over a single infusion time of about 60 minutes.

[0010] In some embodiments, each intravenous infusion of the therapeutic agent comprises about 100 mg to about 400 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof.

[0011] In some embodiments, each intravenous infusion of the therapeutic agent comprises about 200 mg to about 300 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof.

[0012] In some embodiments, each intravenous infusion of the therapeutic agent comprises about 300 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof.

[0013] In some embodiments, the therapeutic agent further comprises other components selected from other drugs, pharmaceutically acceptable carriers, solvents, and buffers.

[0014] In some embodiments, the other components and the compound of Formula (I) and / or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances thereof are not mixed with each other.

[0015] In some embodiments, one or more of the other components are mixed with the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product thereof.

[0016] In some embodiments, the acute bacterial skin and skin structure infection is caused by a Gram-positive bacterial infection.

[0017] In some embodiments, the acute bacterial skin and skin structure infection is caused by Staphylococcus aureus infection and / or coagulase-negative Staphylococcus infection.

[0018] In some embodiments, the Gram-positive bacteria include drug-resistant strains thereof.

[0019] In some embodiments, the Staphylococcus aureus comprises drug-resistant strains thereof, and the coagulase-negative Staphylococcus comprises drug-resistant strains thereof.

[0020] In some embodiments, the method further comprises administering to the patient in need thereof an effective amount of an additional therapeutic agent.

[0021] On the other hand, the present application provides the use of a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof in the preparation of an intravenous infusion therapeutic agent, wherein the therapeutic agent is used to prevent or treat acute bacterial skin and skin structure infections (ABSSSI) or alleviate ABSSSI-related symptoms, and a single infusion dose of the therapeutic agent comprises about 10 mg to about 500 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof, and the therapeutic agent is formulated for intravenous infusion into a patient in need thereof for up to 7 days.

[0022] In some embodiments, the therapeutic agent is formulated for intravenous infusion into the patient in need thereof at intervals of about 8 hours to about 24 hours.

[0023] In some embodiments, the therapeutic agent is formulated for intravenous infusion into the patient in need thereof at intervals of about 12 hours.

[0024] In some embodiments, the therapeutic agent is formulated for administration to the patient in need thereof by intravenous infusion over a period of about 20 minutes to about 3 hours per administration.

[0025] In some embodiments, the therapeutic agent is formulated for administration to the patient in need thereof as an intravenous infusion over a period of about 60 minutes.

[0026] In some embodiments, the therapeutic agent comprises about 100 mg to about 400 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof in a single intravenous infusion.

[0027] In some embodiments, the therapeutic agent comprises about 200 mg to about 300 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof in a single intravenous infusion.

[0028] In some embodiments, the therapeutic agent comprises about 300 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof in a single intravenous infusion.

[0029] In some embodiments, the therapeutic agent further comprises other components selected from other drugs, pharmaceutically acceptable carriers, solvents, and buffers.

[0030] In some embodiments, the other components and the compound of Formula (I) and / or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances thereof are not mixed with each other.

[0031] In some embodiments, one or more of the other components are mixed with the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product thereof.

[0032] In some embodiments, the acute bacterial skin and skin structure infection is caused by a Gram-positive bacterial infection.

[0033] In some embodiments, the Gram-positive bacteria include drug-resistant strains thereof.

[0034] In some embodiments, the acute bacterial skin and skin structure infection is caused by Staphylococcus aureus infection and / or coagulase-negative Staphylococcus infection.

[0035] In some embodiments, the Staphylococcus aureus comprises drug-resistant strains thereof, and the coagulase-negative Staphylococcus comprises drug-resistant strains thereof.

[0036] In some embodiments, the therapeutic agent is formulated for co-administration with an effective amount of another therapeutic agent to the patient in need thereof. DETAILED DESCRIPTION

[0037] The following describes the implementation of the present invention through specific embodiments. People familiar with this technology can easily understand other advantages and effects of the present invention from the contents disclosed in this specification.

[0038] Definition of terms

[0039] In this application, the term "patient in need thereof" generally includes human patients and other mammalian subjects receiving prophylactic or therapeutic treatment, including but not limited to non-human primates, experimental animals such as rabbits, dogs, rats and mice, and other animals. These "patients in need thereof" can be, for example, subjects with a confirmed specific disease, subjects receiving treatment related to a specific disease, subjects with a tendency or risk of developing a specific disease, etc.

[0040] In this application, the term "therapeutic agent" generally refers to a compound, a mixture of compounds, a composition, a biomacromolecule or an extract made from a biological material that can induce a desired therapeutic effect, prevent a certain disease, or alleviate a related disease when properly administered to a patient.

[0041] In this application, the term "pharmaceutically acceptable salt" generally refers to conventional acid- or base-addition salts that retain the biological efficacy and properties of the parent compound (e.g., the compound shown in formula (I)). By way of example only, acid-addition salts can be formed from suitable non-toxic organic or inorganic acids, sample acid-addition salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, phosphoric acid and nitric acid, and those derived from organic acids such as p-toluenesulfonic acid, naphthalenesulfonic acid, naphthalenedisulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoroacetic acid, etc.; base-addition salts include those derived from inorganic bases such as sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts and magnesium salts, and salts derived from organic bases such as primary, secondary and tertiary amines. Chemical modification of (drug) compounds into salts is a well-known technique for pharmaceutical chemists to obtain improved physical and chemical stability, hygroscopicity, fluidity and solubility of the compounds. See, e.g., Ansel, H., et al., Pharmaceutical Dosage Forms and Drug Delivery Systems, 6th ed., 1995.

[0042] In this application, the terms "solvate" and "solvate" are used interchangeably and generally refer to an association or complex of one or more solvent molecules with the salt-type compound of the present application. Examples of solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid, and ethanolamine. The term "hydrate" generally refers to a complex in which the solvent molecule is water.

[0043] In the present application, the term "prodrug" generally refers to the prodrug substance that can be metabolized to form a substance having the structure of the compound of the present application after being administered to a patient; the term "metabolite" generally refers to the substance obtained by the metabolism of the compound of the present application after being administered to a patient, and the prodrugs and metabolites contained in such derivatives are included in the scope of the invention of the present application.

[0044] In this application, the terms "deuterated compound" and "deuterated compound" are used interchangeably, and generally refer to a new compound obtained by replacing one or more hydrogen atoms in an organic compound with a deuterium atom.

[0045] In this application, the term "drug" generally refers to a molecule with the desired biological effect. The drug can be preventive or therapeutic. The drug may include, but is not limited to: protein molecules, including but not limited to peptides, polypeptides, proteins, including post-translationally modified proteins, fusion proteins, antibodies, etc.; small molecules, including inorganic or organic compounds; nucleic acid molecules, including but not limited to double-stranded or single-stranded DNA, or double-stranded or single-stranded RNA (such as antisense (molecules), RNAi, etc.), intron sequences, triple-helical nucleic acid molecules and aptamers; or vaccines (such as Lister and non-Lister vaccines). The drug can be obtained from any known organism (including but not limited to: animals, plants, bacteria, fungi and protozoa or viruses) or a synthetic molecule library.

[0046] In this application, the term "pharmaceutically acceptable carrier" generally refers to one or more non-toxic materials that do not interfere with the effectiveness of the biological activity of the active ingredient. Such preparations can conventionally contain salts, buffers, preservatives, compatible carriers and optionally other therapeutic agents. Such pharmaceutically acceptable preparations can also include compatible solid or liquid fillers, diluents or encapsulating materials suitable for administration to people. Other envisioned carriers, excipients, and / or additives that can be used in the formulations described herein may include, for example, flavorings, antimicrobials, sweeteners, antioxidants, antistatic agents, lipids, protein excipients (such as serum albumin, gelatin, casein), salt-forming counterions (such as sodium), etc. These and other known pharmaceutical carriers, excipients and / or additives suitable for use in the formulations described herein are known in the art and are listed, for example, in "Remington: The Science & Practice of Pharmacy," 21st edition, Lippincott Williams & Wilkins (2005) and "Physician's Desk Reference," 60th edition, Medical Economics, Montvale, New Jersey (2005). Suitable pharmaceutically acceptable carriers can be routinely selected for the desired or required mode of administration, solubility and / or stability.

[0047] In this application, the term "mixing" generally refers to the process of combining one or more compounds, cells, molecules, etc. in the same area. This can be done, for example, in a test tube, petri dish, or any container that allows mixing of one or more compounds, cells, or molecules.

[0048] In this application, the term "administer" generally refers to introducing the drug or a composition comprising the drug (e.g., a therapeutic agent provided herein) into the patient's body by any introduction or delivery route. Any method known to those skilled in the art for contacting cells, organs, or tissues with the drug or its composition can be used.

[0049] In this application, the term "comprising" generally refers to including the features specified but not excluding other elements. The terms "above", "below" or "within" generally refer to excluding the number in question.

[0050] In this application, the term "selected from" generally refers to the selected objects and all combinations thereof. For example, "selected from (:) A, B and C" means all combinations of A, B and C, for example, A, B, C, A+B, A+C, B+C or A+B+C.

[0051] In this application, the terms "effective amount" or "effective dose" are used interchangeably and generally refer to an amount sufficient to achieve or at least partially achieve the desired therapeutic effect. When used in a patient in need, it generally refers to an amount sufficient to cure a patient already suffering from a disease or at least partially prevent the disease and its complications. The effective amount for this use will depend on the severity of the patient's infection and the overall state of the patient's own immune system.

[0052] In this application, the term "co-administration" generally refers to the administration of a therapeutic agent described herein with another therapeutic agent or drug as a single formulation or as multiple independent formulations. Co-administration can be simultaneous or sequential in any order, for example, preferably for a period of time while two (or all) active pharmaceutical ingredients simultaneously exert their biological activities. The therapeutic agent described herein and the other therapeutic agent are not necessarily administered by the same route of administration.

[0053] In this application, the term "about" or "approximately" is generally within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" or "approximately" can mean within 1 or more than 1 standard deviation according to the practice in the art. Alternatively, "about" or "approximately" can mean a range of up to 10% or 20% (i.e., ±10% or ±20%). For example, about 3 mg can include any amount between 2.7 mg and 3.3 mg (for 10%) or between 2.4 mg and 3.6 mg (for 20%). In addition, particularly with respect to biological systems or processes, the term can mean a value of up to one order of magnitude or a value of up to 5 times. When a specific value or composition is provided in this specification and the appended claims, unless otherwise indicated, the meaning of "about" or "approximately" should be assumed to be within an acceptable error range for that specific value or composition.

[0054] Detailed Description of the Invention

[0055] In one aspect, the present application provides a method for preventing or treating acute bacterial skin and skin structure infections (ABSSSI), or alleviating a condition associated with the ABSSSI, comprising administering to a patient in need thereof an intravenous infusion of a therapeutic agent for up to 7 days, wherein each intravenous infusion comprises from about 10 mg to about 500 mg of a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite, or deuterated form thereof. For example, the method may comprise administering to the patient in need thereof an intravenous infusion of the therapeutic agent for 1 day, 2 days, 3 days, 4 days, 5 days, or 6 days. For example, the therapeutic agent may contain a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance thereof in an amount of about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, In some embodiments, the therapeutic agent may include about 100 mg to about 400 mg of the compound shown in formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance. For example, the therapeutic agent may contain about 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg or 400 mg of the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance. In some embodiments, the therapeutic agent may contain about 200 mg to about 300 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated form thereof.For example, the therapeutic agent may contain about 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, or 300 mg of the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite, or deuterated substance. Exemplarily, the therapeutic agent may contain about 300 mg of the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite, or deuterated substance.

[0056] In some embodiments, the method comprises administering the therapeutic agent to the patient in need thereof at intervals of about 8 hours to about 24 hours. For example, the method comprises administering the therapeutic agent to the patient in need thereof at intervals selected from the following: about every 8 hours, about every 9 hours, about every 10 hours, about every 11 hours, about every 12 hours, about every 13 hours, about every 14 hours, about every 15 hours, about every 16 hours, about every 17 hours, about every 18 hours, about every 19 hours, about every 20 hours, about every 21 hours, about every 22 hours, about every 23 hours, and about every 24 hours. During the period of administering the therapeutic agent to the patient in need thereof for a period of 7 days as described herein, the infusion may be maintained at the same time interval, or the time interval of the infusion may be changed according to the actual needs of the patient or in accordance with a doctor's order. For example, the method comprises administering the therapeutic agent to the patient in need thereof at intervals of about 12 hours.

[0057] In some embodiments, the single infusion time of the intravenous infusion is about 20 minutes to about 3 hours. For example, the sustainable single infusion time of the intravenous infusion can be about: 20 minutes, 30 minutes, 40 minutes, 50 minutes, 60 minutes (1 hour), 70 minutes, 80 minutes, 90 minutes, 100 minutes, 110 minutes, 120 minutes (2 hours), 130 minutes, 140 minutes, 150 minutes, 160 minutes, 170 minutes or 180 minutes (3 hours). Further, in some embodiments, the single intravenous infusion can be sustainable for 60 ± 10 minutes. For example, the intravenous infusion can have a sustained bolus infusion time of about 50 minutes, 51 minutes, 52 minutes, 53 minutes, 54 minutes, 55 minutes, 56 minutes, 57 minutes, 58 minutes, 59 minutes, 60 minutes, 61 minutes, 62 minutes, 63 minutes, 64 minutes, 65 minutes, 66 minutes, 67 minutes, 68 minutes, 69 minutes, or 70 minutes. For example, the intravenous infusion can have a sustained bolus infusion time of about 60 minutes.

[0058] In some embodiments, the therapeutic agent further comprises other components selected from other drugs, pharmaceutically acceptable carriers, solvents and buffers. For example, the other components and the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances do not mix with each other. For example, the not mixing with each other may refer to that the other components and the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances are placed in different containers and / or devices. For example, the not mixing with each other may refer to that the container or device for placing the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances in the therapeutic agent, and the container or device for placing other components are placed in different storage spaces and / or different storage conditions. For example, the term "non-mixing with each other" may refer to that the other components and the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance are separately packaged and stored in specific measurement units in their respective containers and / or devices. For example, the term "non-mixing with each other" may refer to that the other components and the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance are mixed only before using the therapeutic agent, and the mixing process may include using a mixing device included or not included in the therapeutic agent, transferring the other components and the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance to a container or device where another component is placed for mixing, and / or transferring the other components and the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance to another container or device for mixing.

[0059] In some embodiments, the therapeutic agent comprises other components selected from other drugs, pharmaceutically acceptable carriers, solvents and buffers, and one or more of the other components are mixed with the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances. For example, the mutual mixing may refer to one or more of the other components being mixed with the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances and placed in the same container or device. For example, the mutual mixing may refer to one or more of the other components being mixed with the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances and then stored in the same or different containers or devices in specific metered units. For example, the mutual mixing may refer to that after one or more of the other components are mixed with the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance, further sufficient mixing (for example, vigorous shaking is required to ensure sufficient mixing) is required before the therapeutic agent is used.

[0060] In some embodiments, the acute bacterial skin and skin structure infection is caused by Gram-positive bacteria. For example, the Gram-positive bacteria may further include resistant strains thereof. In some embodiments, the acute bacterial skin and skin structure infection is caused by Staphylococcus aureus infection and / or coagulase-negative Staphylococcus infection. For example, the Staphylococcus aureus may further include resistant strains thereof, and the coagulase-negative Staphylococcus may further include resistant strains thereof. Specifically, the coagulase-negative Staphylococcus may be selected from Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus xylinus, Staphylococcus haemolyticus, Staphylococcus capitis, Staphylococcus warneri, Staphylococcus mimicus, Staphylococcus xylosus, and Staphylococcus simianus. In the present application, the resistant strain may be resistant to rifamycin (e.g., rifampicin) alone, resistant to quinolones or quinolones alone, or resistant to rifamycins and quinolones. For example, the resistant strains may also be resistant to other antibiotics, including resistance to macrolides such as clarithromycin, azithromycin, and roxithromycin; resistance to nitroimidazoles such as metronidazole, ornidazole, premanide, and delamanide; resistance to aminoglycosides such as streptomycin and amikacin; resistance to β-lactams such as methicillin, ampicillin, and amoxicillin; resistance to tetracyclines such as tetracycline, tigecycline, and minocycline; resistance to oxazolidinones such as linezolid and tedizolid; resistance to nitrofurans such as furazolidone; resistance to polypeptides such as vancomycin and polymyxins; resistance to diarylquinolines such as bedaquiline and clofazimine, etc.

[0061] In some embodiments, the method further comprises administering an effective amount of other therapeutic agents to the patient in need. For example, the method further comprises administering an effective amount of other therapeutic agents to the patient by injection (e.g., intravenous injection, intramuscular injection and / or subcutaneous injection), oral administration, intracavitary administration, enteral administration and / or transdermal absorption. For example, the other therapeutic agents may be selected from antibacterial agents, anesthetics, analgesics, sedatives, hormones, anti-inflammatory drugs, anticoagulants, platelet aggregation inhibitors, antipyretics, cell membrane permeation agents and muscle relaxants, etc.

[0062] On the other hand, the present application provides a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance thereof for use in the preparation of an intravenous infusion therapeutic agent for preventing or treating acute bacterial skin and skin structure infection (ABSSSI) or alleviating the ABSSSI-related condition, wherein a single infusion dose of the therapeutic agent comprises about 10 mg to about 500 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance thereof, and the therapeutic agent is formulated for intravenous infusion into a patient in need thereof for up to 7 days. For example, the therapeutic agent is formulated for intravenous infusion into the patient in need thereof for 1 day, 2 days, 3 days, 4 days, 5 days or 6 days. For example, the therapeutic agent may contain a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance thereof in an amount of about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, In some embodiments, the therapeutic agent may include about 100 mg to about 400 mg of the compound shown in formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance. For example, the therapeutic agent may contain about 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg or 400 mg of the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance.In some embodiments, the therapeutic agent may include about 200mg to about 300mg of the compound shown in formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance. For example, the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance included in the therapeutic agent may be about: 200mg, 210mg, 220mg, 230mg, 240mg, 250mg, 260mg, 270mg, 280mg, 290mg or 300mg. Exemplarily, the therapeutic agent may include about 300mg of the compound shown in formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance.

[0063] In some embodiments, the therapeutic agent is formulated to be suitable for intravenous infusion to the patient in need every about 8 hours to every about 24 hours. For example, the therapeutic agent is formulated to be suitable for intravenous infusion to the patient in need at an interval optionally selected from the following: about every 8 hours, about every 9 hours, about every 10 hours, about every 11 hours, about every 12 hours, about every 13 hours, about every 14 hours, about every 15 hours, about every 16 hours, about every 17 hours, about every 18 hours, about every 19 hours, about every 20 hours, about every 21 hours, about every 22 hours, about every 23 hours, and about every 24 hours. During the period when the therapeutic agent described in the present application is continuously infused intravenously to the patient in need for less than 7 days, the therapeutic agent can be formulated to be suitable for intravenous infusion at the same time interval, or a therapeutic agent suitable for different infusion time intervals can be formulated according to the actual needs of the patient or in accordance with the doctor's orders. For example, the therapeutic agent is formulated for intravenous infusion into the patient in need thereof at intervals of about 12 hours.

[0064] In some embodiments, the therapeutic agent is formulated to be suitable for being applied to the patient in need with an intravenous infusion time of about 20 minutes to about 3 hours at a time. For example, the therapeutic agent is formulated to be suitable for being applied to the patient in need with an optional single infusion time described below: about 20 minutes, about 30 minutes, about 40 minutes, about 50 minutes, about 60 minutes (1 hour), about 70 minutes, about 80 minutes, about 90 minutes, about 100 minutes, about 110 minutes, about 120 minutes (2 hours), about 130 minutes, about 140 minutes, about 150 minutes, about 160 minutes, about 170 minutes and about 180 minutes (3 hours). Further, in some embodiments, the therapeutic agent is formulated to be suitable for being applied to the patient in need with a single infusion time of 60 ± 10 minutes. For example, the therapeutic agent is formulated to be suitable for being administered to the patient in need thereof over a single infusion time optionally selected from the following: 50 minutes, 51 minutes, 52 minutes, 53 minutes, 54 minutes, 55 minutes, 56 minutes, 57 minutes, 58 minutes, 59 minutes, 60 minutes, 61 minutes, 62 minutes, 63 minutes, 64 minutes, 65 minutes, 66 minutes, 67 minutes, 68 minutes, 69 minutes, or 70 minutes. For example, the therapeutic agent is formulated to be suitable for being administered to the patient in need thereof over a single infusion time of about 60 minutes.

[0065] In some embodiments, the therapeutic agent further comprises other components selected from other drugs, pharmaceutically acceptable carriers, solvents and buffers. For example, the other components and the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances do not mix with each other. For example, the not mixing with each other may refer to that the other components and the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances are placed in different containers and / or devices. For example, the not mixing with each other may refer to that the container or device for placing the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances in the therapeutic agent, and the container or device for placing other components are placed in different storage spaces and / or different storage conditions. For example, the term "non-mixing with each other" may refer to that the other components and the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance are separately packaged and stored in specific measurement units in their respective containers and / or devices. For example, the term "non-mixing with each other" may refer to that the other components and the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance are mixed only before using the therapeutic agent, and the mixing process may include using a mixing device included or not included in the therapeutic agent, transferring the other components and the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance to a container or device where another component is placed for mixing, and / or transferring the other components and the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance to another container or device for mixing.

[0066] In some embodiments, the therapeutic agent comprises other components selected from other drugs, pharmaceutically acceptable carriers, solvents and buffers, and one or more of the other components are mixed with the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances. For example, the mutual mixing may refer to one or more of the other components being mixed with the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances and placed in the same container or device. For example, the mutual mixing may refer to one or more of the other components being mixed with the compound of formula (I) and / or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances and then stored in the same or different containers or devices in specific metered units. For example, the mutual mixing may refer to that after one or more of the other components are mixed with the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance, further sufficient mixing (for example, vigorous shaking is required to ensure sufficient mixing) is required before the therapeutic agent is used.

[0067] In some embodiments, the acute bacterial skin and skin structure infection is caused by Gram-positive bacteria. For example, the Gram-positive bacteria may further include resistant strains thereof. In some embodiments, the acute bacterial skin and skin structure infection is caused by Staphylococcus aureus infection and / or coagulase-negative Staphylococcus infection. For example, the Staphylococcus aureus may further include resistant strains thereof, and the coagulase-negative Staphylococcus may further include resistant strains thereof. Specifically, the coagulase-negative Staphylococcus may be selected from Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus xylinus, Staphylococcus haemolyticus, Staphylococcus capitis, Staphylococcus warneri, Staphylococcus mimicus, Staphylococcus xylosus, and Staphylococcus simianus. In the present application, the resistant strain may be resistant to rifamycin (e.g., rifampicin) alone, resistant to quinolones or quinolones alone, or resistant to rifamycins and quinolones. For example, the resistant strains may also be resistant to other antibiotics, including resistance to macrolides such as clarithromycin, azithromycin, and roxithromycin; resistance to nitroimidazoles such as metronidazole, ornidazole, premanide, and delamanide; resistance to aminoglycosides such as streptomycin and amikacin; resistance to β-lactams such as methicillin, ampicillin, and amoxicillin; resistance to tetracyclines such as tetracycline, tigecycline, and minocycline; resistance to oxazolidinones such as linezolid and tedizolid; resistance to nitrofurans such as furazolidone; resistance to polypeptides such as vancomycin and polymyxins; resistance to diarylquinolines such as bedaquiline and clofazimine, etc.

[0068] In some embodiments, the therapeutic agent is formulated to be suitable for co-administration with an effective amount of other therapeutic agents to the patient in need. For example, the therapeutic agent can be formulated to be suitable for co-administration with an effective amount of other therapeutic agents to the patient in need, wherein the other therapeutic agents can be administered by injection (e.g., intravenous injection, intramuscular injection and / or subcutaneous injection), oral administration, intracavitary administration, enteral administration and / or transdermal absorption to the patient. For example, the other therapeutic agents can be selected from antibacterial agents, anesthetics, analgesics, sedatives, hormones, anti-inflammatory drugs, anticoagulants, platelet aggregation inhibitors, antipyretics, cell membrane permeation agents and muscle relaxants, etc.

[0069] Without intending to be bound by any theory, the following embodiments are merely intended to illustrate the methods and uses of the present application and are not intended to limit the scope of the present invention.

[0070] Example

[0071] Example 1

[0072] Analysis of the effectiveness of the treatment method of this application

[0073] 1. Experimental Methods

[0074] In this example, eligible patients were randomly assigned to one of the following two treatment groups: (1) Group A: patients received intravenous infusions of about 60 minutes each time every 12 hours (q12h) for at least 3 days, with each infusion containing 300 mg of the compound of formula (I). After the early assessment (EA) time window of 48 to 72 hours after the first dose, the patients were clinically judged to stop treatment, continue to receive the intravenous infusion treatment (intravenous treatment for a maximum of 14 days), or switch to oral treatment with a systemic antibacterial drug active against Gram-positive microorganisms ( (2) Group B: Receive at least 3 days of intravenous infusion every 12 hours (q12h) for approximately 60 minutes each time, with each infusion of the therapeutic agent being 15 mg / kg of vancomycin, and after the early assessment (EA) time window of 48 to 72 hours after the first dose, the subject will stop treatment, continue to receive the intravenous infusion treatment (intravenous treatment shall not exceed 14 days) or switch to oral treatment with a systemic antibacterial drug active against Gram-positive microorganisms (it is necessary to determine whether the conversion criteria are met). Then, in the ITT, mITT and micro-ITT populations defined in the following table, the early clinical response (percentage) at the EA visit of the subjects who received intravenous infusion of the compound of formula (I) and the subjects who received intravenous infusion of vancomycin were compared.

[0075] 2. Experimental Results and Analysis

[0076] Table 1 Early clinical response at the early assessment visit (ITT / mITT / micro-ITT population) Note: CI = confidence interval; n = number of responders in each population; N = total number of subjects in each population. Percentages were calculated as 100 × (n / N). a: 95% CI for the response rate calculated using exact (Clopper-Pearson) confidence limits. b: The CI for the difference between the response rate to compound (I) and the response rate to vancomycin was calculated based on the Miettinen-Nurminen method.

[0077] The results in Table 1 show that in the group treated with the compound of formula (I) and the group treated with vancomycin, the ITT population response rates were 76.3% and 67.5%, respectively, the mITT population response rates were 76.9% and 67.5%, respectively, and the micro-ITT population response rates were 80.4% and 65.5%, respectively. It can be seen that the therapeutic effect of the compound of formula (I) is better than that of vancomycin.

[0078] Table 2 Early clinical response at the early assessment visit by baseline pathogen (micro-ITT population) Note: N = number of subjects in the micro-ITT population, N1 = number of subjects in the micro-ITT population with a specific baseline pathogen, n = number of responders in a specific category, percentage calculation formula is 100×(n / N1).

[0079] Enumeration Methodology: Subjects with the same pathogen in more than one specimen were counted once for that pathogen. Subjects with the same pathogen identified in blood and primary ABSSSI cultures were counted only once. Subjects with coexisting MRSA and MSSA, CRSA or CSSA, RRSA, and RSSA were counted once for the entire S. aureus line. Response was based on early clinical response at the EA visit.

[0080] The results in Table 2 show that the response rates of the subjects in the treatment group of the compound of formula (I) against common drug-resistant bacteria were higher than those in the vancomycin treatment group.

Claims

1. A method for preventing or treating acute bacterial skin and skin structure infection (ABSSSI), or alleviating symptoms associated with the ABSSSI, comprising intravenously infusing a therapeutic agent to a patient in need thereof for no more than 7 days, wherein each intravenous infusion of the therapeutic agent comprises about 10 mg to about 500 mg of a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product thereof, 2. The method of claim 1, comprising intravenously infusing the therapeutic agent to the patient in need thereof at intervals of about 8 hours to about 24 hours.

3. The method of any one of claims 1-2, comprising administering an intravenous infusion of the therapeutic agent to the patient in need thereof at intervals of about 12 hours.

4. The method according to any one of claims 1-3, wherein the single infusion time of the intravenous infusion is about 20 minutes to about 3 hours.

5. The method according to any one of claims 1-4, wherein the single infusion time of the intravenous infusion is about 60 minutes.

6. The method according to any one of claims 1 to 5, wherein each intravenous infusion of the therapeutic agent comprises about 100 mg to about 400 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product thereof.

7. The method according to any one of claims 1-6, wherein each intravenous infusion of the therapeutic agent comprises about 200 mg to about 300 mg of the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product.

8. The method according to any one of claims 1 to 7, wherein each intravenous infusion of the therapeutic agent comprises about 300 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product thereof.

9. The method according to any one of claims 1 to 8, wherein the therapeutic agent further comprises other components selected from other drugs, pharmaceutically acceptable carriers, solvents and buffers.

10. The method according to claim 9, wherein the other components and the compound of formula (I) and / or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances thereof are not mixed with each other.

11. The method according to claim 9, wherein one or more of the other components are mixed with the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product thereof.

12. The method of any one of claims 1-11, wherein the acute bacterial skin and skin structure infection is caused by a Gram-positive bacterial infection.

13. The method of any one of claims 1-12, wherein the acute bacterial skin and skin structure infection is caused by Staphylococcus aureus infection and / or coagulase-negative Staphylococcus infection. The method according to claim 12 , wherein the Gram-positive bacteria comprise drug-resistant strains thereof.

15. The method according to claim 13, wherein the Staphylococcus aureus comprises drug-resistant strains thereof, and the coagulase-negative Staphylococcus comprises drug-resistant strains thereof.

16. The method of any one of claims 1-15, further comprising administering to the patient in need thereof an effective amount of an additional therapeutic agent.

17. Use of a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance thereof in the preparation of an intravenous infusion therapeutic agent, wherein the therapeutic agent is used to prevent or treat acute bacterial skin and skin structure infection (ABSSSI) or alleviate ABSSSI-related symptoms, and a single infusion dose of the therapeutic agent comprises about 10 mg to about 500 mg of a compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated substance thereof, and the therapeutic agent is formulated for intravenous infusion into a patient in need thereof for up to 7 days.

18. The use according to claim 17, wherein the therapeutic agent is formulated for intravenous infusion into the patient in need thereof at intervals of about 8 hours to about 24 hours.

19. The use according to any one of claims 17-18, wherein the therapeutic agent is formulated for intravenous infusion into the patient in need thereof at intervals of about 12 hours.

20. The use according to any one of claims 17-19, wherein the therapeutic agent is formulated to be administered to the patient in need thereof by intravenous infusion for a period of about 20 minutes to about 3 hours each time.

21. The use according to any one of claims 17 to 20, wherein the therapeutic agent is formulated to be administered to the patient in need thereof by intravenous infusion over a period of about 60 minutes each time.

22. The use according to any one of claims 17-21, wherein the therapeutic agent comprises about 100 mg to about 400 mg of the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product in a single intravenous infusion.

23. The use according to any one of claims 17-22, wherein the therapeutic agent comprises about 200 mg to about 300 mg of the compound of formula (I) and / or its pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product in a single intravenous infusion.

24. The use according to any one of claims 17-23, wherein the therapeutic agent comprises about 300 mg of the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product thereof in a single intravenous infusion.

25. The use according to any one of claims 17 to 24, wherein the therapeutic agent further comprises other components selected from other drugs, pharmaceutically acceptable carriers, solvents and buffers.

26. The use according to claim 25, wherein the other components and the compound of formula (I) and / or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, metabolites or deuterated substances thereof are not mixed with each other.

27. The use according to claim 25, wherein one or more of the other components are mixed with the compound of formula (I) and / or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, metabolite or deuterated product thereof.

28. The use according to any one of claims 17 to 27, wherein the acute bacterial skin and skin structure infection is caused by a Gram-positive bacterial infection.

29. The use according to claim 28, wherein the Gram-positive bacteria comprises drug-resistant strains thereof.

30. The use according to any one of claims 17 to 29, wherein the acute bacterial skin and skin structure infection is caused by Staphylococcus aureus infection and / or coagulase-negative Staphylococcus infection.

31. The use according to claim 30, wherein the Staphylococcus aureus comprises drug-resistant strains thereof, and the coagulase-negative Staphylococcus comprises drug-resistant strains thereof.

32. The use according to any one of claims 17-31, wherein the therapeutic agent is formulated to be co-administered to the patient in need thereof with an effective amount of another therapeutic agent.

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