Pharmaceutical composition comprising oxazolidinone derivative

Abstract

A pharmaceutical composition according to one aspect of the present invention comprises: an oxazolidinone derivative represented by chemical formula 1 or a pharmaceutically acceptable salt thereof; a binder; and a disintegrant, and thus corresponds to a preparation having high stability and immediate release properties. Therefore, the pharmaceutical composition can be used as an antibiotic having low toxicity, excellent efficacy, an excellent drug release rate, and high stability.

Description

Pharmaceutical composition containing oxazolidinone derivatives

[0001] This invention relates to a pharmaceutical composition comprising an oxazolidinone derivative.

[0002]

[0003] Since the oxazolidinone antibiotic linezolid was first reported in 1984 (European Patent Publication No. 127,902), various oxazolidinone derivatives have been reported by several pharmaceutical companies. However, among the drugs currently under development, there is no drug that is less toxic and more effective than linezolid (product name: Zyvox). This problem arises because, although linezolid is receiving attention as the best alternative to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), if the recently reported linezolid-resistant strains spread further, there could be a problem where there are virtually no treatments available. For this reason, there is an urgent need to develop a drug that is superior to linezolid in terms of efficacy or toxicity and is effective against linezolid-resistant strains.

[0004] In addressing pain relief, drugs generally need to be rapidly absorbed into the circulating blood. Therefore, for oral formulations, it is of paramount importance that the drug is already completely or partially dissolved while present in gastric fluid. Consequently, if the drug is not absorbed through the gastric mucosa, it can be prepared for absorption upon entering the upper intestinal tract, such as the duodenum. While weak acids may dissolve better in intestinal fluid, drug dissolution is slow within the duodenum because the duodenum itself contains a limited amount of fluid.

[0005] Immediate-release formulations are preparations that enhance convenience by reducing the frequency of drug administration, and their dissolution patterns can be determined by the inherent characteristics of the drug. Immediate-release formulations have the advantage of increasing convenience by reducing the number of doses, while the degree of dissolution does not change significantly depending on the amount of active ingredients or changes in the manufacturing method.

[0006] Therefore, there is a need to develop new substances that provide oxazolidinone derivatives with low toxicity and excellent efficacy, while also possessing excellent drug release rates and high stability.

[0007]

[0008] One aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof;

[0009] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0010] The present invention provides a pharmaceutical composition comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose potassium, sodium starch glycolate, crospovidone, starch, and gelatinized starch:

[0011] [Chemical Formula 1]

[0012]

[0013] (In the above chemical formula 1,

[0014] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0015] The above n is an integer from 0 to 2;

[0016] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0017] ;

[0018] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0019] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0020] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0021] The above m is one integer from 1 to 6;

[0022] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0023] The above R 41 It is a (C1-C6) alkyl.

[0024] Another aspect is the step of obtaining a first mixture by mixing an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof and a disintegrant;

[0025] A step of obtaining a second mixture by mixing the first mixture and the binder above.

[0026] The method includes the step of mixing the second mixture and the disintegrant to obtain a third mixture;

[0027] The above binder is one or more selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose;

[0028] The present invention provides a method for preparing a pharmaceutical composition in which the disintegrant is one or more selected from the group consisting of sodium croscarmellose, calcium carboxymethylcellulose, sodium starch glycolate, crospovidone, starch, and pregelatinized starch:

[0029] [Chemical Formula 1]

[0030] ,

[0031] (In the above chemical formula 1,

[0032] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0033] The above n is an integer from 0 to 2;

[0034] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures:

[0035] ;

[0036] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0037] The above R 31 and R 32are independently hydrogen, (C1-C6) alkyl or -C(=O)H;

[0038] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0039] The above m is one integer from 1 to 6;

[0040] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0041] The above R 41 It is a (C1-C6) alkyl.

[0042] Another aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof;

[0043] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0044] The present invention provides an antibiotic composition comprising one or more disintegrants selected from the group consisting of sodium croscarmellose, calcium carboxymethylcellulose, sodium starch glycolate, crospovidone, starch, and pregelatinized starch:

[0045] [Chemical Formula 1]

[0046]

[0047] (In the above chemical formula 1,

[0048] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0049] The above n is an integer from 0 to 2;

[0050] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0051] ;

[0052] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0053] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0054] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0055] The above m is one integer from 1 to 6;

[0056] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0057] The above R 41 It is a (C1-C6) alkyl.

[0058] Another aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof;

[0059] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0060] The present invention provides a pharmaceutical composition for the prevention or treatment of bacterial-mediated diseases comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose potassium, sodium starch glycolate, crospovidone, starch, and gelatinized starch:

[0061] [Chemical Formula 1]

[0062]

[0063] (In the above chemical formula 1,

[0064] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0065] The above n is an integer from 0 to 2;

[0066] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0067]

[0068] ;

[0069] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0070] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0071] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0072] The above m is one integer from 1 to 6;

[0073] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0074] The above R 41 It is a (C1-C6) alkyl.

[0075] Another aspect is to provide a method for preventing or treating a bacterial-mediated disease, comprising the step of administering the above-mentioned pharmaceutical composition to an individual in need thereof.

[0076] Another aspect is to provide the use of the above pharmaceutical composition for the prevention or treatment of bacterial-mediated diseases.

[0077] Another aspect is to provide the use of the above pharmaceutical composition for the manufacture of a drug for the prevention or treatment of bacterial-mediated diseases.

[0078] Another aspect is to provide a method for preventing or treating a bacterial-mediated disease, comprising the step of administering the above-mentioned antibiotic composition to an individual in need thereof.

[0079] Another aspect is to provide the use of the above antibiotic composition for the prevention or treatment of bacterial-mediated diseases.

[0080] Another aspect is to provide the use of the above antibiotic composition for the manufacture of a drug for the prevention or treatment of bacterial-mediated diseases.

[0081]

[0082] One aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof;

[0083] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0084] A pharmaceutical composition is provided comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose potassium, sodium starch glycolate, crospovidone, starch, and gelatinized starch:

[0085] [Chemical Formula 1]

[0086]

[0087] (In the above chemical formula 1,

[0088] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0089] The above n is an integer from 0 to 2;

[0090] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0091] ;

[0092] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0093] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0094] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0095] The above m is one integer from 1 to 6;

[0096] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0097] The above R 41 It is a (C1-C6) alkyl.

[0098] In one embodiment, the above R may be hydrogen.

[0099] In one embodiment, the above Q may be -OH.

[0100] In one embodiment, the oxazolidinone derivative represented by the above chemical formula 1 is

[0101] and It may be a compound represented as one selected from the group consisting of

[0102] In one embodiment, the oxyzolidinone derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof may be a compound represented by Formula 2 below or a pharmaceutically acceptable salt thereof:

[0103] [Chemical Formula 2]

[0104] .

[0105] The oxazolidinone derivative represented by Chemical Formula 1 above may be prepared and used in the form of a prodrug, hydrate, solvate, isomer, or pharmaceutically acceptable salt to enhance in vivo absorption or increase solubility. Accordingly, the oxazolidinone derivative or its pharmaceutically acceptable salt includes its prodrug, hydrate, solvate, isomer, or pharmaceutically acceptable salt.

[0106] The oxazolidinone derivative represented by the above chemical formula 1 may exist in a solvated form, for example, a hydrated form and a nonsolved form, and the solvates of the oxazolidinone derivative represented by the above chemical formula 1 include all solvated forms having pharmaceutical activity.

[0107] The oxazolidinone derivative represented by Chemical Formula 1 above may comprise a prodrug form. The prodrug may be used to modify or improve the physical and / or pharmacokinetic profile of the parent compound and may be formed if it contains a suitable group or substituent that can induce the parent compound to form the prodrug. The prodrug comprises, for example, an in vivo hydrolyzable ester of the oxazolidinone derivative represented by Chemical Formula 1 and a pharmaceutically acceptable salt thereof.

[0108] Various forms of the above-mentioned prodrugs are known in the art, for example, a) literature [Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985) and Methods in Enzymology, Vol. 42, p.309-396, edited by K. Widder, et al. (Academic Press, 1985)]; b) literature [A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 "Design and Application of Prodrugs", by H. Bundgaard p. 113-191 (1991)]; c) literature [H. Bundgaard, Advanced Drug Delivery Reviews, 8, 1-38 (1992)]; d) literature [H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77, 285 (1988)]; and e) You may refer to the literature [N. Kakeya, et al., Chem Pharm Bull, 32, 692 (1984)], etc.

[0109] The above prodrugs may include, for example, the following compounds:

[0110] .

[0111] As shown in the example above, it can be manufactured in a form that is active in the body by attaching a phosphonate or acetyl group to a hydroxyl group, or there are methods such as attaching an amino acid or manufacturing it in the form of a carbonate. The above prodrug is mainly used when solubility or absorption is relatively low, and when modified into a prodrug, not only are solubility and absorption increased, but ADME (absorption, distribution, metabolism, excretion) and PK profile can also be improved.

[0112] The oxazolidinone derivative represented by Chemical Formula 1 above has a chiral center at the C-5 position of the oxazolidinone ring. A preferred diastereomer of the oxazolidinone derivative compound is identical to Chemical Formula 1 above and can exhibit a superior MAO profile compared to the epimer compound represented by Chemical Formula 1b below:

[0113] [Chemical Formula 1b]

[0114] .

[0115] When any mixture of epimers on the chiral center is used, the amount used can be adjusted by taking into account the ratio of diastereomers in order to obtain the same effect with pharmaceutical activity as when using the enantiomer alone.

[0116] Since the oxazolidinone derivative represented by the above chemical formula 1 can exhibit tautomerization, even if only one possible tautomer form is expressed in the chemical formula or reaction formula, it includes any tautomer form having antibacterial activity and is not limited to just the single tautomer form used in the chemical formula or reaction formula.

[0117] The oxazolidinone derivative represented by Chemical Formula 1 above may also exhibit polymorphism and includes any polymorphic compound having antibacterial activity. The oxazolidinone derivative represented by Chemical Formula 1 above can be prepared by various known methods depending on the type of substituent, for example, according to the method exemplified in Reaction Scheme 1 or 2 below. Since the preparation method presented in Reaction Scheme 1 or 2 below is merely an example and can be easily modified by those skilled in the art depending on specific substituents, the method exemplified in Reaction Scheme 1 or 2 below does not limit the method of preparing the oxazolidinone compound represented by Chemical Formula 1 below, and unless otherwise stated, the definition of the substituent in the following reaction scheme is the same as the definition in Chemical Formula 1 above. The oxazolidinone derivative represented by Chemical Formula 1 above can be synthesized by different methods depending on Q above. For example, if the above Q is -OH, it can be synthesized according to the following reaction scheme 1, and if the above Q is N-acetyl, it can be synthesized according to the following reaction scheme 2.

[0118] Specifically, in the case of Reaction Scheme 1, compound I is synthesized by reacting difluoronitrobenzene with ethanolamine, and the alcohol and amine are protected with TBS (t-butyldimethylsilyl) or BOC, respectively (compound II). Then, the nitro group is reduced to an amine using Pd / C (compound III), and a Cbz group is attached using Cbz-Cl to synthesize compound IV. Compound IV is reacted with (R)-glycidyl butyrate and BuLi to synthesize a chiral compound V. In compound V, the alcohol group is first protected with benzoyl, then the BOC and TBS protecting groups are removed with hydrochloric acid (compound VI), and mesylation is performed to synthesize compound VII. Compound VII is reacted with hydrazine and then reacted again with trimethylorthoformate to synthesize cyclic amiderazone compound VIII. From compound VIII, by removing the formyl group (compound IX) and introducing the linking part X and various R, oxazolidinone derivatives represented by the above chemical formula 1 can be obtained:

[0119] [Reaction Equation 1]

[0120] .

[0121] When Q is N-acetyl, compound V synthesized in Reaction Scheme 1 is reacted with methanesulfonyl chloride (Ms-Cl) and then reacted with sodium azide (NaN3) to synthesize compound X. Compound X is converted into an amine using Pd / C under hydrogen gas, and then a cbz group is attached using Cbz-Cl to synthesize compound XII. Compound XII is treated with hydrochloric acid to remove the protecting groups boc and tbs, and then reacted with methanesulfonyl chloride (Ms-Cl) to synthesize compound XIII. Compound XIII is reacted with hydrazine and then with trimethylorthoformate to synthesize cyclic amiderazone compound XIV. After removing the protecting group cbz from compound XIV and introducing an acetyl group (compound XV), the formyl group is removed from compound XV and various R groups are introduced to obtain the compound represented by Chemical Formula 1:

[0122] [Reaction Equation 2]

[0123] .

[0124] The above pharmaceutical composition may be in a form suitable for oral use (e.g., tablets, lozenges, hard or soft capsules, aqueous or oil suspensions, emulsions, dispersible powders or granules, syrups or elixirs).

[0125] Additionally, the pharmaceutical composition may contain one or more known drugs selected from other clinically useful antimicrobial agents (e.g., β-lactams, macrolides, quinolones, or aminoglycosides) and / or other anti-infective agents (e.g., antifungal triazoles or amphotericins) (i.e., by co-formulation) or may be co-administered with one or more of these known drugs. To enhance therapeutic efficacy, they may include carbapenems, e.g., meropenem or imipenem. The pharmaceutical composition may also be formulated with or co-administered with bactericidal / permeability-enhancing protein (BPI) products or efflux pump inhibitors to enhance activity against Gram-negative bacteria and bacteria resistant to antimicrobial agents.

[0126] The above pharmaceutical composition may be formulated with or co-administered with vitamins, for example, vitamin B, for example, vitamin B2, vitamin B6, vitamin B12, and folic acid. The compound of the present invention may be formulated with or co-administered with cyclooxygenase (COX) inhibitors, particularly COX-2 inhibitors. Additionally, the above pharmaceutical composition may be formulated and co-administered with an antimicrobial agent active against Gram-positive or Gram-negative bacteria.

[0127] The above pharmaceutical composition can be obtained by a conventional process using conventional pharmaceutical excipients widely known in the art. Accordingly, a composition intended for oral administration may contain, for example, one or more coloring agents, sweeteners, flavoring agents, and / or preservatives. A pharmaceutical composition intended for intravenous administration may advantageously contain a suitable fungicide, antioxidant, or reducing agent, or a suitable sequestrant (for example, to enhance stability).

[0128] The composition for oral administration may be in the form of a hard gelatin capsule in which the active ingredient is mixed with an inert solid diluent, e.g., calcium carbonate, calcium phosphate, or kaolin, or in the form of a soft gelatin capsule in which the active ingredient is mixed with water or oil, e.g., peanut oil, liquid paraffin, or olive oil.

[0129] Aqueous suspensions generally comprise one or more suspending agents, e.g., sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinyl-pyrrolidone, tragaccand gum, and acacia gum; It contains an active ingredient in a finely divided form, together with a dispersant or wetting agent, e.g., lecithin, or a condensation product of an alkylene oxide and a fatty acid (e.g., polyoxyethylene stearate), or a condensation product of an ethylene oxide and a long-chain aliphatic alcohol, e.g., heptadecaethyleneoxycetanol, or a condensation product of an ethylene oxide and a partial ester derived from a fatty acid and hexitol, e.g., polyoxyethylene sorbitol monooleate, or a condensation product of an ethylene oxide and a long-chain aliphatic alcohol, e.g., heptadecaethyleneoxycetanol, or a condensation product of an ethylene oxide and a partial ester derived from a fatty acid and hexitol, e.g., polyoxyethylene sorbitol monooleate, or a condensation product of an ethylene oxide and a partial ester derived from a fatty acid and hexitol anhydride, e.g., polyethylene sorbitan monooleate. Aqueous suspensions may contain one or more preservatives (e.g., ethyl or propyl p-hydroxybenzoate), antioxidants (e.g., ascorbic acid), coloring agents, flavoring agents and / or sweeteners (e.g., sucrose, saccharin, or aspartame).

[0130] Oil suspensions can be formulated by suspending the active ingredient in vegetable oil (e.g., arachnid oil, olive oil, sesame oil, or coconut oil) or mineral oil (e.g., liquid paraffin). Oil suspensions may also contain thickeners, such as beeswax, hard paraffin, or cetyl alcohol. Sweeteners and flavoring agents as mentioned above can be added to provide a palatable oral formulation. These compositions can be preserved by adding antioxidants such as ascorbic acid.

[0131] Dispersible powders and granules suitable for preparing aqueous suspensions by adding water contain an active ingredient along with a dispersant or wetting agent, a suspending agent, and one or more preservatives. Suitable dispersant or wetting agents and suspending agents are exemplified as previously mentioned. Additional excipients such as sweeteners, flavoring agents, and coloring agents may also be present.

[0132] For additional information regarding formulations, refer to the following literature [Reference: Chapter 25.2 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990].

[0133] The amount of active ingredient combined with one or more excipients to produce a single dosage form will vary depending on the host being treated and the specific route of administration. For example, a formulation intended for oral administration to humans may generally contain 50 mg to 5 g of the active ingredient compound along with a convenient and appropriate amount of excipients (which may be about 5 to about 98% of the total weight of the composition). A dosage unit form will generally contain about 200 mg to about 2 g of the active ingredient. For additional information regarding the route of administration and dosage regimen, refer to the following reference [Reference: Chapter 25.3 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990].

[0134] In one embodiment, the pharmaceutical composition may be administered intravenously, subcutaneously, or intramuscularly to each patient, for example, at a dose of 0.1 mg / kg to 20 mg / kg or 1 mg / kg to 20 mg / kg per day, and an oral dose per day that may be approximately equivalent to the parenteral dose per day may be administered to the patient, and the pharmaceutical composition may be administered 1 to 4 times per day.

[0135] The term "salt" above may be an acid addition salt formed by a free acid, an alkali metal salt (sodium salt, potassium salt, etc.), or an alkaline earth metal salt (calcium salt, magnesium salt, etc.). Inorganic acids and organic acids may be used as the free acid forming the acid addition salt. Inorganic acids may include hydrochloric acid, bromic acid, nitric acid, sulfuric acid, perchloric acid, phosphoric acid, etc., and organic acids may include citric acid, acetic acid, lactic acid, maleic acid, fumaric acid, gluconic acid, methanesulfonic acid, glyconic acid, succinic acid, tartaric acid, galacturonic acid, emvonic acid, glutamic acid, aspartic acid, oxalic acid, (D) or (L) malic acid, maleic acid, methanesulfonic acid, ethanesulfonic acid, 4-toluenesulfonic acid, salicylic acid, citric acid, benzoic acid, or malonic acid.

[0136] The above acid addition salts are, for example, acetate, aspartate, benzate, besylate, bicarbonate / carbonate, bisulfate / sulfate, borate, camsylate, citrate, edicilate, esylate, formate, fumarate, gluteptate, gluconate, glucuronate, hexafluorophosphate, hyperbenzate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, isethionate, lactate, malate, maliate, malonate, mesylate, methyl sulfate, naphthylate, 2-naphthylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, saccharate, stearate, succinate, tartrate, It may be tosylate, trifluoroacetate, aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine, or zinc salt, and specifically may be hydrochloride or trifluoroacetate.

[0137] The above acid addition salt can be prepared, for example, by dissolving an active substance in an organic solvent such as methanol, ethanol, acetone, methylene chloride, or acetonitrile and adding the organic acid or inorganic acid to produce a precipitate, which is then filtered and dried; or by vacuum distilling an organic solvent and an excess amount of acid and then drying, or by crystallizing under an organic solvent.

[0138] In addition, the above alkali metal salt or alkaline earth metal salt can be obtained, for example, by dissolving an active substance in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium, or calcium salts as the metal salts. In addition, the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0139] The above term “pharmaceutically acceptable salt” means a salt prepared using a compound according to one aspect and a relatively non-toxic acid or base. When the compound contains relatively acidic functional groups, a base addition salt may be obtained by contacting a sufficient amount of base with the neutral form of the compound in a pure solution or a suitable inert solvent. Pharmaceutically acceptable base addition salts include salts of sodium, potassium, calcium, ammonium, organic amines, or magnesium, or similar salts. When the compound contains relatively basic functional groups, an acid addition salt may be obtained by contacting a sufficient amount of acid with the neutral form of the compound in a pure solution or a suitable inert solvent. Pharmaceutically acceptable acid addition salts include salts of inorganic acids such as hydrochloric acid, hydrobromide, nitric acid, carbonic acid, bicarbonate, phosphoric acid, monohydrogen phosphate, dihydrogen phosphate, sulfuric acid, hydrogen sulfate, hydroiodic acid, or phosphoric acid, and salts of organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, souveric acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, and methanesulfonic acid, and further include salts of amino acids (e.g., arginine) and salts of organic acids such as glucuronic acid.

[0140] The above pharmaceutically acceptable salts can be synthesized by conventional chemical methods from parent compounds containing an acidic or basic portion. Generally, such salts are prepared by reacting the free acid or base form of these compounds with a stoichiometrically appropriate amount of base or acid in water, an organic solvent, or a mixture of both. Generally, the medium may be a non-aqueous medium such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile.

[0141] The oxazolidinone derivative represented by the above chemical formula 1 exhibits antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus and Enterococcus faecalis, and Gram-negative bacteria such as Haemophilus influenzae and Moraxella catarrhalis, which are resistant to existing antibiotics, at much lower concentrations than currently commercially available linezolid, and can have excellent antibacterial activity, particularly against linezolid-resistant Enterococcus faecium.

[0142] The term "binder" above refers to a substance that helps maintain a specific form by binding the components of a drug together during the drug manufacturing process, and which can improve the mechanical strength of a tablet, control the release of the drug, or regulate its fluidity or stability.

[0143] In one embodiment, the binder may be one or more selected from the group consisting of povidone, hypromellose, and hydroxypropylcellulose.

[0144] In one embodiment, the binder may be included in an amount of 4 to 45 wt%, 4 to 40 wt%, 4 to 30 wt%, 4 to 20 wt%, 4 to 15 wt%, 4 to 12 wt%, 6 to 45 wt%, 6 to 40 wt%, 6 to 30 wt%, 6 to 20 wt%, 6 to 15 wt%, 6 to 12 wt%, 8 to 45 wt%, 8 to 40 wt%, 8 to 30 wt%, 8 to 20 wt%, 8 to 15 wt%, or 8 to 12 wt% based on the total weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof. If the binder is included in an amount of less than 4% by weight relative to the weight of the oxazolidinone derivative or its pharmaceutically acceptable salt, or in an amount exceeding 45% by weight, the dissolution rate of the pharmaceutical composition within one or more times selected from the group consisting of 5, 10, 15, 30, and 45 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution may be reduced.

[0145] In one embodiment, the binder may be 2 to 8 weight%, 2 to 7 weight%, 2 to 6.5 weight%, 2.5 to 8 weight%, 2.5 to 7 weight%, 2.5 to 6.5 weight%, 3 to 8 weight%, 3 to 7 weight% to 6.5 weight%, 4 to 8 weight%, 4 to 7 weight%, or 4 to 6.5 weight% relative to the total weight of the pharmaceutical composition. If the binder is included in an amount less than 2 weight% or more than 8 weight% relative to the total weight of the pharmaceutical composition, the dissolution rate of the pharmaceutical composition within one or more times selected from the group consisting of 5, 10, 15, 30, and 45 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution may be reduced.

[0146] The term "disintegrant" above refers to a substance that plays a role in facilitating the rapid and effective release of a drug within the body; it swells or decomposes upon contact with water, blood, buffer solutions, or digestive fluids, and causes the formulation to break down into small particles or drugs.

[0147] In one embodiment, the disintegrant may be one or more selected from the group consisting of croscarmellose sodium and carboxymethylcellulose calcium.

[0148] In one embodiment, the disintegrant may be included in an amount of 5 to 45 wt%, 5 to 40 wt%, 5 to 30 wt%, 5 to 20 wt%, 5 to 15 wt%, 6 to 45 wt%, 6 to 40 wt%, 6 to 30 wt%, 6 to 20 wt%, 6 to 15 wt%, 9 to 45 wt%, 9 to 40 wt%, 9 to 30 wt%, 9 to 20 wt%, or 9 to 15 wt% based on the weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof. If the above disintegrant is included in an amount of less than 5% by weight relative to the weight of the oxazolidinone derivative or its pharmaceutically acceptable salt, or in an amount exceeding 45% by weight, the dissolution rate of the pharmaceutical composition within one or more times selected from the group consisting of 5, 10, 15, 30, and 45 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution may be reduced.

[0149] In one embodiment, the disintegrant may be included in an amount of 3 to 10 wt%, 3 to 9 wt%, 3 to 8 wt%, 3 to 7.5 wt%, 3.5 to 10 wt%, 3.5 to 9 wt%, 3.5 to 8 wt%, 3.5 to 7.5 wt%, 4 to 10 wt%, 4 to 9 wt%, 4 to 8 wt%, or 4 to 7.5 wt% relative to the total weight of the pharmaceutical composition. If the disintegrant is included in an amount of less than 3 wt% relative to the total weight of the pharmaceutical composition or in an amount exceeding 10 wt%, the dissolution rate of the pharmaceutical composition within one or more times selected from the group consisting of 5, 10, 15, 30, and 45 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution may be reduced.

[0150] In one embodiment, the binder and the disintegrant may be included in a weight ratio of 1:0.5 to 1.8, 1:0.5 to 1.5, 1:0.5 to 1.4, 1:0.6 to 1.8, 1:0.6 to 1.5, 1:0.6 to 1.4, 1:0.7 to 1.8, 1:0.7 to 1.5, or 1:0.7 to 1.4. If the binder and the disintegrant are included in a weight ratio of less than 1:0.5 or in a weight ratio exceeding 1:1.8, the dissolution rate of the pharmaceutical composition within one or more times selected from the group consisting of 5, 10, 15, 30, and 45 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution may be reduced.

[0151] In one embodiment, the pharmaceutical composition may further comprise one or more lubricants selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, tartaric acid, sodium lauryl sulfate, polyethylene glycol, and sodium stearyl fumarate; specifically, the pharmaceutical composition may further comprise one or more lubricants selected from the group consisting of magnesium stearate, calcium stearate, and tartaric acid.

[0152] The term "lubricant" above refers to a substance that reduces friction during the compression and molding processes of tablets or capsules in the drug manufacturing process, facilitates smooth mechanical processing, and enables the smooth ingestion of the formulation.

[0153] In one embodiment, the lubricant may be included in an amount of 1 to 12 weight%, 1 to 8 weight%, 1 to 4 weight%, 2 to 12 weight%, 2 to 8 weight%, 2 to 4 weight%, 2.5 to 12 weight%, 2.5 to 8 weight%, or 2.5 to 4 weight% relative to the weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof.

[0154] In one embodiment, the lubricant may be included in an amount of 1 to 3 weight%, 1 to 2.5 weight%, 1 to 2 weight%, 1.3 to 3 weight%, 1.3 to 2.5 weight%, 1.3 to 2 weight%, 1.4 to 3 weight%, 1.4 to 2.5 weight%, or 1.4 to 2 weight% relative to the total weight of the pharmaceutical composition.

[0155] In one embodiment, the pharmaceutical composition may further comprise one or more fillers selected from the group consisting of microcrystalline cellulose, lactose monohydrate, lactose, mannitol, sorbitol, glucose, sucrose, maltose, calcium phosphate, and dextrin, and specifically, the pharmaceutical composition may further comprise one or more fillers selected from the group consisting of microcrystalline cellulose, lactose monohydrate, and lactose.

[0156] The term "filler" above refers to a substance added to a drug formulation to regulate the amount of the drug or improve the physical properties of the formulation, and corresponds to a substance capable of controlling the size, mechanical properties, solubility, absorption, etc. of the formulation.

[0157] In one embodiment, the filler may be included in an amount of 45 to 500 wt%, 45 to 250 wt%, 45 to 100 wt%, 45 to 55 wt%, 48 to 500 wt%, 48 to 250 wt%, 48 to 100 wt%, 48 to 55 wt%, 50 to 500 wt%, 50 to 250 wt%, 50 to 100 wt%, or 50 to 55 wt% relative to the weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof.

[0158] In one embodiment, the filler may be included in an amount of 25 to 70 weight%, 25 to 50 weight%, 25 to 35 weight%, 26 to 70 weight%, 26 to 50 weight%, 26 to 35 weight%, 27 to 70 weight%, 27 to 50 weight%, or 27 to 35 weight% based on the total weight of the pharmaceutical composition.

[0159] In one embodiment, the pharmaceutical composition may further comprise one or more coating agents selected from the group consisting of hypromellose, polyethylene glycol, ethylene glycol, vinyl alcohol graft copolymer, talc, titanium oxide, titanium dioxide, glyceryl monocaprylocaprate Type 1, and polyvinyl alcohol.

[0160] The term "coating agent" above refers to a substance that performs a specific function by forming a thin layer on the surface of a drug formulation, particularly a tablet or capsule. The coating agent can improve not only the physical properties of the drug formulation but also drug release, stability, or the patient's experience of taking the medication.

[0161] In one embodiment, the coating agent may be included in an amount of 5 to 30 wt%, 5 to 20 wt%, 5 to 10 wt%, 5 to 8 wt%, 5.3 to 30 wt%, 5.3 to 20 wt%, 5.3 to 10 wt%, 5.3 to 8 wt%, 5.5 to 30 wt%, 5.5 to 20 wt%, 5.5 to 10 wt%, or 5.5 to 8 wt% relative to the weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof.

[0162] In one embodiment, the coating agent may be included in an amount of 2 to 5 weight%, 2 to 4.5 weight%, 2 to 4 weight%, 2.5 to 5 weight%, 2.5 to 4.5 weight%, 2.5 to 4 weight%, 3 to 5 weight%, 3 to 4.5 weight%, or 3 to 4 weight% relative to the weight of the oxyzolidinone derivative or a pharmaceutically acceptable salt thereof.

[0163] In one embodiment, the pharmaceutical composition may be an immediate-release formulation.

[0164] The term "immediate-release" above means that the dissolution pattern of the drug is determined according to the inherent characteristics of the drug. Specifically, the immediate-release formulation may include a formulation in which 10 to 50 weight% of the drug is dissolved within 5 minutes, 30 to 80 weight% within 10 minutes, 55 to 90 weight% within 15 minutes, and 80 to 99 weight% within 30 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution. The pharmaceutical composition may be used as an immediate-release formulation by comprising the oxazolidinone derivative or a pharmaceutically acceptable salt thereof, the binder, and the disintegrant.

[0165] In one embodiment, the pharmaceutical composition may be eluted within 5 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution, in an amount of 10 to 50 wt%, 10 to 45 wt%, 10 to 43 wt%, 15 to 50 wt%, 15 to 45 wt%, 15 to 43 wt%, 20 to 50 wt%, 20 to 45 wt%, or 20 to 43 wt% relative to the total weight of the pharmaceutical composition.

[0166] In one embodiment, the pharmaceutical composition may be eluted within 10 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution, in an amount of 30 to 80 wt%, 30 to 75 wt%, 30 to 70 wt%, 35 to 80 wt%, 35 to 75 wt%, 35 to 70 wt%, 40 to 80 wt%, 40 to 75 wt%, or 40 to 70 wt% relative to the total weight of the pharmaceutical composition.

[0167] In one embodiment, the pharmaceutical composition may be eluted within 15 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution, in an amount of 55 to 90 wt%, 55 to 85 wt%, 55 to 80 wt%, 60 to 90 wt%, 60 to 85 wt%, 60 to 80 wt%, 65 to 90 wt%, 65 to 85 wt%, or 65 to 80 wt% relative to the total weight of the pharmaceutical composition.

[0168] In one embodiment, the pharmaceutical composition may be eluted within 30 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution, in an amount of 80 to 99 weight%, 80 to 97 weight%, 80 to 95 weight%, 82 to 99 weight%, 82 to 97 weight%, 82 to 95 weight%, 85 to 99 weight%, 85 to 97 weight%, or 85 to 95 weight% relative to the total weight of the pharmaceutical composition.

[0169] In one embodiment, the pharmaceutical composition may be eluted within 45 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution, in an amount of 90 to 99.9 wt%, 90 to 99 wt%, 90 to 98 wt%, 91 to 99.9 wt%, 91 to 98 wt%, 92 to 99.9 wt%, 92 to 99 wt%, or 92 to 98 wt% relative to the total weight of the pharmaceutical composition.

[0170] In one embodiment, the pharmaceutical composition may be a formulation for oral or parenteral administration, specifically, the pharmaceutical composition may be a formulation for oral, transdermal, subcutaneous, intravenous, or intramuscular administration, and more specifically, the pharmaceutical composition may be a formulation for oral administration.

[0171] In one embodiment, the pharmaceutical composition may be one selected from the group consisting of tablets, pills, soft capsules, hard capsules, pills, powders, granules, lyophilized agents, lozenges, powders, solutions, syrups, suppositories, patches, sprays, inhalants, gels, and injectables. Specifically, the pharmaceutical composition may be a tablet.

[0172] In one embodiment, the pharmaceutical composition may be used for the prevention or treatment of bacterial-mediated diseases.

[0173] In one embodiment, the bacteria may be one or more selected from acid-fast bacteria, Gram-negative bacteria, and Gram-positive bacteria.

[0174] The term "acid-fast bacteria" above refers to bacteria that have a wax-like hydrophobic cell wall with a high mycholic acid content within the cell wall. Acid-fast bacteria correspond to bacteria that are difficult to classify through Gram staining because the dye does not penetrate well during Gram staining. Acid-fast bacteria may be, for example, tuberculosis bacteria or non-tuberculosis acid-fast bacteria, and more specifically, may be tuberculosis mycobacterium (Mycobacterium tuberculosis), abscessus mycobacterium (Mycobacterium abscessus), mycobacterium avium complex (MAC), or mycobacterium kansasii.

[0175] In one embodiment, the bacteria are Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium avium complex (MAC), Mycobacterium kansasii, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas It may be selected from a group consisting of *Aeruginosa*, *Klebsiella pneumoniae*, *Acinetobacter baumannii*, and *Escherichia coli*.

[0176] In one embodiment, the bacteria may be antibiotic-resistant. In one embodiment, the antibiotic-resistant bacteria may be bacteria resistant to one or more antibiotics, and the antibiotics may be calicheamicin (e.g., calicheamicin gamma I, calicheamicin omega I), enediyne antibiotics, esperamicin, aclacinomysins, actinomycin (e.g., dactinomycin, cactinomycin), anthramycin, azacerine, bleomycins, carabicin, carninomycin, carzinophilin, chromomycins, carbapenem antibiotics (e.g., doripenem, imipenem), It may be one or more selected from the group consisting of meropenem, aminoglycoside antibiotics (e.g., amikacin, gentamicin), oxazolidinone antibiotics (e.g., linezolid, sutezolid), fluoroquinolone antibiotics (e.g., levofloxacin, moxifloxacin), diarylquinoline antibiotics (e.g., bedaquiline), and glycopeptide antibiotics (e.g., vancomycin).

[0177] In one embodiment, the bacteria may be linezolid-resistant Enterococcus faecium.

[0178] In one embodiment, the bacteria may be a multidrug-resistant strain.

[0179] The term "multidrug-resistant" means having resistance to at least one drug in each of several types of antibiotics, for example, two or more different antimicrobial categories, preferably three or more antimicrobial categories. Specifically, the multidrug-resistant strain may be, for example, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium, or vancomycin-resistant Staphylococcus aureus (VRSA).

[0180] In one embodiment, the bacterial-mediated disease may be a disease involving an infection occurring in a tissue selected from the group consisting of dermis, hair follicles, muscles, joints, blood, endocardium, subcutaneous tissue, bone, and lungs, or it may be a systemic disease.

[0181] In one embodiment, the bacterial-mediated disease may be selected from the group consisting of tuberculosis, non-tuberculosis mycobacterial disease, abscess, furuncle, folliculitis, skin infection, bacteremia, sepsis, endocarditis, cellulitis, necrotizing soft tissue infections, osteomyelitis, septic arthritis, and pneumonia.

[0182] The above pharmaceutical composition can exhibit excellent therapeutic or preventive effects against the above bacteria-mediated disease based on an excellent antibacterial effect, and can have high stability and persistence by including the above binder and the above disintegrant.

[0183] The term "prevention" above may refer to any act of inhibiting the progression of a disease in an individual or delaying its onset by administering a pharmaceutical composition according to one aspect.

[0184] The term "treatment" above may refer to any act in which the symptoms of an individual's disease are improved or beneficially altered by the administration of a pharmaceutical composition according to one aspect.

[0185] A pharmaceutical composition according to one aspect comprises an oxazolidinone derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof, the binder, and the disintegrant, and corresponds to a formulation having high stability and immediate release. Accordingly, the pharmaceutical composition can be used as an antibiotic having low toxicity and excellent efficacy, as well as excellent drug release rate and high stability.

[0186]

[0187] In one embodiment, it was confirmed that the pharmaceutical composition meets the finished drug product evaluation criteria (content, purity, uniformity, dissolution rate, or stability). Specifically, it was confirmed that the composition contains the same compound by confirming in HPLC or UV spectrum analysis that the peak positions of the standard solution for testing and the composition under testing are identical and the peak area is 90 to 110% relative to the standard solution for testing. Additionally, it was confirmed in a purity test that the impurity content is less than the evaluation standard value of 2%, and in a formulation uniformity test that it is 1.3% to 3.4%, which is much lower than the standard value of less than 15.0%. Furthermore, it was confirmed in a dissolution rate test that at least 75% of the composition is dissolved within 30 minutes. Specifically, it was confirmed that at least 89.9% and an average of 91.9% are dissolved. In addition, it was confirmed that the composition has high stability by being able to be stored for 12 to 60 months or more under long-term storage conditions at 25°C and 60% relative humidity, and for 6 months or more under accelerated storage conditions at 40°C and 75% relative humidity (see Example 1).

[0188] In another example, the dissolution characteristics of the pharmaceutical composition were analyzed. Specifically, each preparation example (12 tablets per preparation example) was added to 900 mL of water, and the dissolution rate over time was checked while mixing at 50 rpm. As a result, the dissolution rates after 5, 10, 15, 30, and 45 minutes based on the input time were confirmed to be 12, 36, 62, 89, and 92% for Preparation Example 1, 42, 72, 85, 92, and 93% for Preparation Example 2, 22, 45, 69, 92, and 94% for Preparation Example 3, 20, 42, 59, 88, and 95% for Preparation Example 4, 10, 37, 55, 83, and 97% for Preparation Example 5, 24, 53, 73, 96, and 99% for Preparation Example 9, and 33, 49, 65, 91, and 99% for Preparation Example 10, respectively, confirming that all preparation examples have excellent dissolution capabilities (see Example 2).

[0189]

[0190] Another aspect is the step of obtaining a first mixture by mixing an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof and a disintegrant;

[0191] A step of obtaining a second mixture by mixing the first mixture and the binder above.

[0192] The method includes the step of mixing the second mixture and the disintegrant to obtain a third mixture;

[0193] The above binder is one or more selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose;

[0194] The present invention provides a method for preparing a pharmaceutical composition in which the disintegrant is one or more selected from the group consisting of sodium croscarmellose, calcium carboxymethylcellulose, sodium starch glycolate, crospovidone, starch, and pregelatinized starch:

[0195] [Chemical Formula 1]

[0196]

[0197] (In the above chemical formula 1,

[0198] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0199] The above n is an integer from 0 to 2;

[0200] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures:

[0201] ;

[0202] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0203] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl or -C(=O)H;

[0204] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6)alkyl;

[0205] The above m is one integer from 1 to 6;

[0206] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0207] The above R 41 It is a (C1-C6) alkyl.

[0208] The above terms "oxazolidinone derivative," "pharmaceuticalally acceptable salt," "binder," "disintegrant," etc., are within the scope described above.

[0209] In one embodiment, at the step of obtaining the first mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the disintegrant may be mixed in a weight ratio of 1:0.03 to 0.25, 1:0.03 to 0.2, 1:0.03 to 0.15, 1:0.05 to 0.25, 1:0.05 to 0.2, or 1:0.05 to 0.15.

[0210] In one embodiment, in the step of obtaining the first mixture, one or more fillers selected from the group consisting of microcrystalline cellulose, lactose monohydrate, lactose, mannitol, sorbitol, glucose, sucrose, maltose, calcium phosphate, and dextrin may be further mixed.

[0211] The above term "filler" is within the aforementioned scope.

[0212] In one embodiment, when the filler is further mixed in the step of obtaining the first mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the filler may be included in a ratio of 1:0.2 to 5, 1:0.2 to 3, 1:0.2 to 1, 1:0.4 to 5, 1:0.4 to 3, 1:0.4 to 1, 1:0.5 to 5, 1:0.5 to 3, or 1:0.5 to 1.

[0213] In one embodiment, in the step of obtaining the first mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof, the disintegrant, and the filler may be mixed in a dry state or a wet state.

[0214] In one embodiment, the manufacturing method may further include the step of sieving the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the disintegrant prior to the step of obtaining the first mixture.

[0215] In one embodiment, the manufacturing method may further include a step of sieving the filler prior to the step of obtaining the first mixture.

[0216] The above sieve can be performed using, for example, a 12 to 30 mesh, 12 to 28 mesh, 12 to 26 mesh, 14 to 30 mesh, 14 to 28 mesh, 14 to 26 mesh, 16 to 30 mesh, 16 to 28 mesh, or 16 to 26 mesh mesh.

[0217] In one embodiment, at the step of obtaining the second mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the binder may be mixed in a ratio of 1:0.04 to 0.5, 1:0.04 to 0.4, 1:0.04 to 0.2, 1:0.06 to 0.5, 1:0.6 to 0.4, 1:0.06 to 0.2, 1:0.1 to 0.5, 1:0.1 to 0.4, or 1:0.1 to 0.2.

[0218] In one embodiment, in the step of obtaining the second mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the binder may be mixed in a wet state.

[0219] Through the step of obtaining the second mixture above, a granule comprising the oxazolidinone derivative or a pharmaceutically acceptable salt thereof can be obtained.

[0220] In one embodiment, the manufacturing method may further include a step of sieving the second mixture prior to the step of obtaining the third mixture. The filtration may be performed, for example, by extruding the second mixture through a mesh of 2 to 30 mesh, 2 to 26 mesh, 2 to 22 mesh, 4 to 30 mesh, 4 to 26 mesh, 4 to 22 mesh, 8 to 30 mesh, 8 to 26 mesh, or 8 to 22 mesh.

[0221] In one embodiment, the manufacturing method may further include a step of drying the filtered second mixture prior to the step of obtaining the third mixture. The drying may be performed, for example, at 50 to 70°C. Through the step of drying the second mixture, the drying loss of the filtered second mixture may be reduced.

[0222] In one embodiment, the manufacturing method may further include a step of milling the dried second mixture prior to the step of obtaining the third mixture. The milling may be performed, for example, using a mesh of 16 to 30 mesh, 16 to 28 mesh, 16 to 26 mesh, 18 to 30 mesh, 18 to 28 mesh, 18 to 26 mesh, 15 to 30 mesh, 15 to 28 mesh, or 15 to 26 mesh.

[0223] In one embodiment, at the step of obtaining the third mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the disintegrant may be mixed in a weight ratio of 1:0.01 to 0.3, 1:0.01 to 0.2, 1:0.01 to 0.15, 1:0.012 to 0.03, 1:0.012 to 0.2, 1:0.012 to 0.15, 1:0.02 to 0.3, 1:0.02 to 0.2, or 1:0.02 to 0.15.

[0224] In one embodiment, in the step of obtaining the third mixture, one or more fillers selected from the group consisting of microcrystalline cellulose, lactose monohydrate, lactose, mannitol, sorbitol, glucose, sucrose, maltose, calcium phosphate, and dextrin may be further mixed.

[0225] In one embodiment, when one or more fillers are further mixed in the step of obtaining the third mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the filler may be mixed in a weight ratio of 1:0.05 to 0.5, 1:0.05 to 0.45, 1:0.05 to 0.4, 1:0.1 to 0.5, 1:0.1 to 0.45, or 1:0.1 to 0.4.

[0226] In one embodiment, the manufacturing method may further include the step of obtaining a fourth mixture by mixing the third mixture with one or more lubricants selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, tartaric acid, sodium lauryl sulfate, polyethylene glycol, and sodium stearyl fumarate.

[0227] In one embodiment, at the step of obtaining the fourth mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the lubricant may be mixed in a weight ratio of 1:0.01 to 0.15, 1:0.01 to 0.12, 1:0.01 to 0.05, 1:0.015 to 0.15, 1:0.015 to 0.12, 1:0.015 to 0.05, 1:0.02 to 0.15, 1:0.02 to 0.12, or 1:0.02 to 0.05.

[0228] In one embodiment, the manufacturing method may further include the step of obtaining a solid formulation by pressing the fourth mixture after the step of obtaining the fourth mixture.

[0229] The above term "solid dosage form" may be, for example, a tablet, and specifically, the solid dosage form comprises an average mass of 600 to 800 mg, 600 to 750 mg, 600 to 720 mg, 650 to 800 mg, 650 to 750 mg, 650 to 720 mg, 680 to 800 mg, 680 to 750 mg, or 680 to 720 mg, an individual mass of 600 to 800 mg, 600 to 750 mg, 600 to 720 mg, 650 to 800 mg, 650 to 750 mg, 650 to 720 mg, 680 to 800 mg, 680 to 750 mg, or 680 to 720 mg, and 5 to 25 kP, 5 to 24 It may be a tablet having an individual strength of kP, 5 to 22 kP, 8 to 25 kP, 8 to 24 kP, 8 to 22 kP, 10 to 25 kP, 10 to 24 kP, or 10 to 22 kP.

[0230] In one embodiment, the manufacturing method may further include, after the step of obtaining the solid formulation, the step of coating the solid formulation with one or more coating agents selected from the group consisting of hypromellose, polyethylene glycol, ethylene glycol, vinyl alcohol graft copolymer, talc, titanium oxide, titanium dioxide, type 1 glycerol monocaprylcaprate, and polyvinyl alcohol.

[0231] In one embodiment, the coating step may be performed under an air supply temperature of 40 to 75°C, 40 to 70°C, 40 to 65°C, 45 to 75°C, 45 to 70°C, 45 to 65°C, 50 to 75°C, 50 to 70°C, or 50 to 65°C, and an exhaust temperature of 40 to 65°C, 40 to 63°C, 40 to 60°C, 43 to 65°C, 43 to 63°C, 43 to 60°C, 45 to 65°C, 45 to 63°C, or 45 to 60°C.

[0232] In one embodiment, the manufacturing method may further include a step of polishing the coated solid formulation after the coating step. The polishing may be performed, for example, using carnauba wax.

[0233] According to a method for preparing the above pharmaceutical composition according to another aspect, by including an oxazolidinone derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof, the binder, and the disintegrant, a formulation having high stability and immediate release can be prepared. The formulation prepared therefrom can be used as an antibiotic having low toxicity and excellent efficacy, as well as excellent drug release rate and high stability.

[0234]

[0235] Another aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof;

[0236] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0237] The present invention provides an antibiotic composition comprising one or more disintegrants selected from the group consisting of sodium croscarmellose, calcium carboxymethylcellulose, sodium starch glycolate, crospovidone, starch, and pregelatinized starch:

[0238] [Chemical Formula 1]

[0239]

[0240] (In the above chemical formula 1,

[0241] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0242] The above n is an integer from 0 to 2;

[0243] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0244]

[0245] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0246] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0247] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0248] The above m is one integer from 1 to 6;

[0249] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0250] The above R 41 It is a (C1-C6) alkyl.

[0251] The above terms "oxazolidinone derivative," "pharmaceuticalally acceptable salt," "binder," "disintegrant," etc., are within the scope described above.

[0252] The term "antibiotic" above refers to a compound that exhibits the effects of inhibiting the growth, inhibiting the proliferation, and killing microorganisms such as bacteria, viruses, and fungi, and corresponds to one that can be used for the prevention or treatment of various infectious diseases.

[0253] In one embodiment, the antibiotic composition may have a growth-inhibiting, proliferation-inhibiting, or killing effect on one or more bacteria selected from the group consisting of acid-fast bacteria, Gram-positive bacteria, and Gram-negative bacteria.

[0254] The above term "acid-fast bacteria" is within the aforementioned range.

[0255] Specifically, the antibiotic composition comprises Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium avium complex (MAC), Mycobacterium kansasii, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas It may have growth inhibitory, proliferation inhibitory, or killing effects on one or more bacteria selected from the group consisting of *Aeruginosa*, *Klebsiella pneumoniae*, *Acinetobacter baumannii*, and *Escherichia coli*.

[0256] In one embodiment, the antibiotic composition may have an effect of inhibiting growth, inhibiting proliferation, or killing antibiotic-resistant bacteria. Specifically, the antibiotic composition comprises calicheamicin (e.g., calicheamicin gamma I, calicheamicin omega I), enediyne antibiotics, esperamicin, aclacinomysins, actinomycin (e.g., dactinomycin, cactinomycin), anthramycin, azacerine, bleomycins, carabicin, carninomycin, carzinophilin, chromomycins, carbapenem antibiotics (e.g., doripenem, imipenem, meropenem), aminoglycoside antibiotics (e.g., It may have growth-inhibiting, proliferation-inhibiting, or killing effects on bacteria resistant to one or more antibiotics selected from the group consisting of amikacin, gentamicin, oxazolidinone antibiotics (e.g., linezolid, sutezolid), fluoroquinolone antibiotics (e.g., levofloxacin, moxifloxacin), diarylquinoline antibiotics (e.g., bedaquiline), and glycopeptide antibiotics (e.g., vancomycin).

[0257] In one embodiment, the antibiotic composition may have a growth inhibitory, proliferation inhibitory, or killing effect on Enterococcus faecium that is resistant to linezolid.

[0258] In one embodiment, the antibiotic composition may have a growth inhibitory, proliferation inhibitory, or killing effect on multidrug-resistant strains.

[0259] The above term "multidrug resistance" is within the aforementioned scope.

[0260] An antibiotic composition according to another aspect may exhibit high antibiotic efficacy against strains by including the oxazolidinone derivative or a pharmaceutically acceptable salt thereof, and by including the binder and the excipient, it may be used as an antibiotic with low toxicity, excellent efficacy, excellent drug release rate, and high stability.

[0261]

[0262] Another aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof;

[0263] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0264] The present invention provides a pharmaceutical composition for the prevention or treatment of bacterial-mediated diseases comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose potassium, sodium starch glycolate, crospovidone, starch, and gelatinized starch:

[0265] [Chemical Formula 1]

[0266]

[0267] (In the above chemical formula 1,

[0268] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0269] The above n is an integer from 0 to 2;

[0270] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0271] ;

[0272] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0273] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0274] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0275] The above m is one integer from 1 to 6;

[0276] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0277] The above R 41 It is a (C1-C6) alkyl.

[0278] The above terms "oxazolidinone derivative," "pharmaceuticalally acceptable salt," "binder," "disintegrant," "prevention," "treatment," etc., are within the scope described above.

[0279] A pharmaceutical composition according to another aspect comprises an oxazolidinone derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof, the binder, and the disintegrant, and corresponds to a formulation having high stability and immediate release. Accordingly, the pharmaceutical composition can be used as a treatment for bacterial-mediated diseases that has low toxicity and excellent efficacy, as well as excellent drug release rate and high stability.

[0280]

[0281] Another aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof;

[0282] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0283] A method for preventing or treating a bacterial-mediated disease is provided, comprising the step of administering to an individual in need a pharmaceutical composition comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose potassium, sodium starch glycolate, crospovidone, starch, and gelatinized starch:

[0284] [Chemical Formula 1]

[0285]

[0286] (In the above chemical formula 1,

[0287] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0288] The above n is an integer from 0 to 2;

[0289] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0290] ;

[0291] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0292] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0293] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0294] The above m is one integer from 1 to 6;

[0295] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0296] The above R 41 It is a (C1-C6) alkyl.

[0297] The above terms "oxazolidinone derivative," "pharmaceuticalally acceptable salt," "binder," "disintegrant," "prevention," "treatment," etc., are within the scope described above.

[0298] According to a method of prevention or treatment according to another aspect, by including a pharmaceutical composition comprising an oxazolidinone derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof, the binder and the disintegrant, excellent effects such as increased overall cure rate, elimination of mediating bacteria, inhibition of increased severity, inhibition of adverse event occurrence, increased safety and tolerability can be exhibited, and excellent preventive or therapeutic efficacy against bacterial-mediated diseases can be exhibited.

[0299]

[0300] Another aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof;

[0301] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0302] The present invention provides a pharmaceutical composition comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose potassium, sodium starch glycolate, crospovidone, starch, and gelatinized starch for the prevention or treatment of bacterial-mediated diseases:

[0303] [Chemical Formula 1]

[0304]

[0305] (In the above chemical formula 1,

[0306] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0307] The above n is an integer from 0 to 2;

[0308] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0309] ;

[0310] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0311] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0312] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0313] The above m is one integer from 1 to 6;

[0314] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0315] The above R 41 It is a (C1-C6) alkyl.

[0316] The above terms "oxazolidinone derivative," "pharmaceuticalally acceptable salt," "binder," "disintegrant," "prevention," "treatment," etc., are within the scope described above.

[0317] According to another aspect of the use of a pharmaceutical composition, by including a pharmaceutical composition comprising an oxazolidinone derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof, the binder, and the disintegrant, excellent effects such as increased overall healing rate, elimination of mediating bacteria, inhibition of increased severity, inhibition of adverse events, increased safety, and increased tolerability can be exhibited, and excellent preventive or therapeutic efficacy against bacterial-mediated diseases can be exhibited.

[0318]

[0319] Another aspect is an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof for the manufacture of a drug for the prevention or treatment of bacterial-mediated diseases;

[0320] One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and

[0321] The present invention provides a use of a pharmaceutical composition comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose potassium, sodium starch glycolate, crospovidone, starch, and gelatinized starch:

[0322] [Chemical Formula 1]

[0323]

[0324] (In the above chemical formula 1,

[0325] The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and;

[0326] The above n is an integer from 0 to 2;

[0327] The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures;

[0328] ;

[0329] The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen;

[0330] The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H;

[0331] The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl;

[0332] The above m is one integer from 1 to 6;

[0333] The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is;

[0334] The above R 41 It is a (C1-C6) alkyl.

[0335] The above terms "oxazolidinone derivative," "pharmaceuticalally acceptable salt," "binder," "disintegrant," "prevention," "treatment," etc., are within the scope described above.

[0336] According to another aspect of the use of the pharmaceutical composition, by including a pharmaceutical composition comprising an oxazolidinone derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof, the binder and the disintegrant, excellent effects such as increased overall healing rate, elimination of mediating bacteria, inhibition of increased severity, inhibition of adverse events, increased safety and tolerability can be exhibited, and excellent preventive or therapeutic efficacy against bacterial-mediated diseases can be exhibited.

[0337]

[0338] A pharmaceutical composition according to one aspect comprises an oxazolidinone derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof, the binder, and the disintegrant, and corresponds to a formulation having high stability and immediate release. Accordingly, the pharmaceutical composition can be used as an antibiotic having low toxicity and excellent efficacy, as well as excellent drug release rate and high stability.

[0339]

[0340] Figure 1 is a figure showing the dissolution rate in water over time of a pharmaceutical composition containing an oxazolidinone derivative.

[0341] Figure 2 is a figure showing the dissolution rate in water over time of a pharmaceutical composition containing an oxazolidinone derivative.

[0342] Figure 3 is a figure showing the dissolution rate in water over time of a pharmaceutical composition containing an oxazolidinone derivative.

[0343] Figure 4 is a figure showing the dissolution rate in water over time of a pharmaceutical composition containing an oxazolidinone derivative.

[0344] Figure 5 is a figure showing the dissolution rate in water over time of a pharmaceutical composition containing an oxazolidinone derivative.

[0345]

[0346] The present invention will be explained in more detail below through examples. However, these examples are intended to illustrate the invention and the scope of the invention is not limited to these examples.

[0347]

[0348] Reference Example - Preparation of Oxazolidinone Derivatives

[0349] For types of oxazolidinone derivatives and methods for preparing the same, refer to Korean Published Patent No. 10-2011-0088737 and Korean Registered Patent No. 10-1023174.

[0350] In the following preparation examples and embodiments, an oxazolidinone derivative represented by the following chemical formula 2 (hereinafter referred to as Compound 1) was used as the oxazolidinone derivative:

[0351] [Chemical Formula 2]

[0352] .

[0353]

[0354] Preparation Example

[0355] Preparation Example 1. Preparation of a pharmaceutical composition containing an oxazolidinone derivative

[0356] Step 1. Sieving and mixing process

[0357] 400 mg of an oxazolidinone derivative represented by the above chemical formula 2 (hereinafter, compound 1), 110 mg of microcrystalline cellulose, 50 mg of lactose monohydrate, and 20 mg of carboxymethylcellulose calcium were sieved using a 24 Mesh sieve and then mixed in a dry state.

[0358]

[0359] Step 2. Wet granulation process

[0360] After completing Step 1 above, 200 mg of 20% povidone K30 binder was added to the mixture, and wet granulation was performed for 240 seconds under conditions of 90 rpm impeller and 2,900 rpm chopper.

[0361]

[0362] Step 3. Sieving and Drying Process

[0363] After completing Step 2 above, the granulated material was granulated in a wet state using a 17 Mesh screen and dried at 55°C for 6 hours so that the Loss of Drying (LOD) of the material was 0.5 to 2%.

[0364]

[0365] Step 4. Milling and Blending Process

[0366] After completing Step 3 above, the dried material was sifted using a 0.8 mm mesh (approx. 23 to 25 mesh), then 30 mg of microcrystalline cellulose, 10 mg of lactose monohydrate, 20 mg of carboxymethylcellulose calcium, and 13 mg of croscarmellose sodium that passed through a 24 mesh mesh were added, and the mixture was blended for 10 minutes at 25 rpm using a v-blender. Subsequently, 12 mg of magnesium stearate that passed through a 35 mesh mesh was added, and the mixture was blended for another 3 minutes at 25 rpm.

[0367]

[0368] Step 5. Compression Process

[0369] After completing Step 4 above, the mixture was compressed into tablets having an average mass of 705 mg ± 2%, individual masses of 705 mg ± 5%, individual thicknesses of 5.2 to 5.8 mm, individual strengths of 10 to 22 kP, and a disintegration time of less than 30 minutes in purified water.

[0370]

[0371] Step 6. Coating Process

[0372] After completing Step 5 above, the compressed tablet is coated with a solution prepared by mixing 23 mg of hypromellose, 2 mg of polyethylene glycol 6000, 2 mg of talc, 2 mg of titanium oxide, and 230 mg of purified water, then the supply air temperature is set to 75°C to 85°C, the exhaust temperature to 35°C to 45°C, the fan speed to 1 to 5 rpm, and the spray pressure to 0.7 kg / cm² 2 up to 1.0 kg / cm² 2 Coated under conditions.

[0373]

[0374] Step 7. Polishing Process

[0375] After completing Step 6 above, 0.086 mg of carnauba wax per tablet was added to a coating pan and exposed to light at 3 rpm for 5 to 20 minutes.

[0376]

[0377] The composition of Manufacturing Example 1 above is as shown in Table 1 below.

[0378] Preparation Example 1 Active ingredient compound 1400 mg Filler Microcrystalline cellulose (Step 1) 110 mg Microcrystalline cellulose (Step 4) 30 mg Lactose monohydrate (Step 1) 50 mg Lactose monohydrate (Step 4) 10 mg Disintegrant Carboxymethylcellulose calcium (Step 1) 20 mg Carboxymethylcellulose calcium (Step 4) 20 mg Crosscarmellose sodium (Step 4) 13 mg Binder Povidone 40 mg Solvent Purified water 140 mg (evaporated during manufacturing) Lubricant Magnesium stearate 12 mg Coating agent Hypromellose 23 mg Polyethylene glycol 6000 2 mg Talc 2 mg Titanium oxide 2 mg Solvent Purified water 230 mg (evaporated during manufacturing) Total weight 734 mg

[0379]

[0380] Preparation Example 2. Preparation of a pharmaceutical composition containing an oxazolidinone derivative

[0381] Step 1. Sieving and dry-mixing process

[0382] 400 mg of the above compound 1, 150 mg of microcrystalline cellulose, 60 mg of lactose monohydrate, and 20 mg of croscarmellose sodium were sieved using a 20 Mesh sieve, and then mixed in a dry state for 180 seconds under conditions of impeller 150 ± 15 rpm and chopper 3,000 ± 250 rpm.

[0383]

[0384] Step 2. Wet granulation process

[0385] After completing Step 1 above, 245 mg of 18% povidone K30 binder was further added to the mixture, and wet granulation was performed for up to 380 seconds under conditions of impeller 150 ± 50 rpm and chopper 3,000 ± 250 rpm.

[0386]

[0387] Step 3. Sieving, drying, and milling processes

[0388] After completing Step 2 above, the granulated material was granulated in a wet state at 1,500 rpm using a mesh of 6,350 μm (about 2 to 4 mesh). Subsequently, the material was dried using a fluidized bed dryer with air at 50 to 70 ℃ introduced at a flow rate of 100 to 500 CFM so that the drying loss of the material was less than 2%. Subsequently, the material was granulated in a dry state at 1,500 rpm using a mesh of 1,016 μm (about 23 to 25 mesh).

[0389]

[0390] Step 4. Blending Process

[0391] After completing Step 3 above, 5 mg of sodium croscarmellose that had passed through a 30 Mesh sieve was added to the established substance and mixed by rotating it 200 times using a v-blender. Subsequently, 10 mg of magnesium stearate that had passed through a 30 Mesh sieve was added and mixed by rotating it 60 times.

[0392]

[0393] Step 5. Compression Process

[0394] After completing Step 4 above, the mixture was compressed into a tablet form having an average weight of 690 mg ± 2%, an individual weight of 690 mg ± 5%, an individual thickness of 5.0 to 5.6 mm, an individual strength of 11 to 26 kP, and a disintegration time of less than 30 minutes in purified water.

[0395]

[0396] Step 6. Coating Process

[0397] After completing Step 5 above, 166 mg of a 15% aqueous solution of Opadry white (321A180025 QX) containing ethyleneglycol and vinyl alcohol graft copolymer, talc, titanium dioxide, glyceryl monocaprylocaprate Type 1, and polyvinyl alcohol-part hydrolyzed was added to the tablet, and the tablet was coated under conditions of an air supply temperature of 45 to 70°C, an exhaust temperature of 42 to 47°C, an air supply rate of 250 CFM to 450 CFM (average 350 CFM), and a spray rate of 50 to 60 g / min.

[0398] The composition of Manufacturing Example 2 above is as shown in Table 2 below.

[0399] Preparation Example 2 Active ingredient compound 1400 mg Filler Microcrystalline cellulose (Step 1) 150 mg Lactose monohydrate (Step 1) 60 mg Disintegrant Croscarmellose sodium (Step 1) 20 mg Croscarmellose sodium (Step 4) 5 mg Binder Povidone 45 mg Solvent Purified water (200 mg) Lubricant Magnesium stearate 10 mg Coating agent Opadry 321A18002525 mg Coating agent Opadry 03F180009- Solvent Purified water (141 mg) Total weight 715 mg

[0400]

[0401] Preparation Examples 3 to 5. Preparation of pharmaceutical compositions comprising oxazolidinone derivatives

[0402] A pharmaceutical composition was prepared using the same process as in Preparation Example 2 above, but Opadry 03F180009 containing hypromellose, talc, titanium dioxide, and polyethylene glycol 6000 was used as the coating agent, and compositions of Preparation Examples 3 to 5 were prepared by varying the concentrations of the filler, disintegrant, binder, lubricant, or coating agent added at each step.

[0403] The compositions of Manufacturing Examples 3 to 5 above are as shown in Table 3 below.

[0404] Ingredients Preparation Example 3 Preparation Example 4 Preparation Example 5 Active Ingredient Compound 1400 mg 400 mg 400 mg Filler Microcrystalline Cellulose (Step 1) 150 mg 140 mg 150 mg Lactose Monohydrate (Step 1) 60 mg 60 mg 60 mg Disintegrant Croscarmellose Sodium (Step 1) 20 mg 20 mg 20 mg Crosscarmellose Sodium (Step 4) 10 mg 33 mg 5 mg Binder Povidone 40 mg 40 mg 45 mg Solvent Purified Water (183 mg) (183 mg) (200 mg) Lubricant Magnesium Stearate 10 mg 12 mg 10 mg Coating Agent Opadry 321A180025---Coating Agent Opadry 03F180009 22 mg 22 mg 25 mg Solvent Purified Water (120 mg) (120 mg)(135 mg) Total weight 712 mg 727 mg 715 mg

[0405]

[0406] Preparation Examples 6 to 8. Preparation of pharmaceutical compositions comprising oxazolidinone derivatives

[0407] A pharmaceutical composition was prepared using the same process as in Preparation Example 2, but with the concentration of the substance added at each step changed, and in the coating process of Preparation Examples 6 and 7, the supply air temperature was changed to 40°C, and in the coating process of Preparation Example 8, the supply air temperature was 50 to 70°C and the exhaust temperature was 40 to 60°C, thereby preparing the compositions of Preparation Examples 6 to 8, respectively.

[0408] The compositions of Preparation Examples 6 to 8 are as shown in Table 4 below.

[0409] Ingredients Preparation Example 6 Preparation Example 7 Preparation Example 8 Active Ingredient Compound 150 mg 200 mg 400 mg Filler Microcrystalline cellulose (Step 1) 160 mg 55 mg 110 mg Microcrystalline cellulose (Step 4) 15 mg 15 mg 30 mg Lactose monohydrate (Step 1) 70 mg 25 mg 50 mg Lactose monohydrate (Step 4) 5 mg 5 mg 10 mg Disintegrant Carboxymethylcellulose calcium (Step 1) 10 mg 10 mg 20 mg Carboxymethylcellulose calcium (Step 4) 10 mg 10 mg 20 mg Crosscamellose sodium (Step 4) 13 mg Binder Povidone 20 mg 20 mg 40 mg Solvent Purified water 0.04 mL 0.04 mL 0.12 mL Lubricant Magnesium stearate 6 mg 6 mg 12 mg Coating agent Hypromellose 11.5 mg 11.5 mg 23 mg Polyethylene Glycol 6000 1 mg 1 mg 2 mg Talc 1 mg 1 mg 2 mg Titanium Oxide 1 mg 1 mg 2 mg Solvent Ethanol 0.09 mL 0.09 mL - Methylene Chloride 0.09 mL 0.09 mL - Purified Water 0.05 mL Color Yellow No. 5 0.0042 mg 0.0042 mg 0.0084 mg Total Weight 360.5 mg 360.5 mg 734 mg

[0410]

[0411]

[0412] Preparation Examples 9 and 10. Preparation of pharmaceutical compositions containing oxazolidinone derivatives

[0413] Step 1. Sieving and mixing process

[0414] Compound 1, 400 mg, microcrystalline cellulose, 60 mg lactose monohydrate, and 20 mg croscarmellose sodium were sieved using a 20 Mesh screen and then manually mixed in an LDPE bag for 180 seconds in a dry state.

[0415]

[0416] Step 2. Wet granulation process

[0417] After completing Step 1 above, a hypromellose or hydroxypropyl cellulose binder was further added to the mixture and wet granulated manually for 360 seconds.

[0418]

[0419] Step 3. Sieving, drying, and milling processes

[0420] After completing Step 2 above, the granules were sieved in a wet state using an 8-mesh screen. Subsequently, they were dried at 60°C until the drying loss was less than 2%. Afterward, they were sieved in a dry state using a 1,016 μm screen at 2,500 rpm.

[0421]

[0422] Step 4. Blending Process

[0423] After completing Step 3 above, 5 mg of sodium croscarmellose that had passed through a 30 Mesh sieve was added to the granulated material and mixed by rotating it 200 times with a V-blender. Subsequently, 10 mg of magnesium stearate that had passed through a 30 Mesh sieve was added and mixed by rotating it 60 times with a V-blender.

[0424]

[0425] Step 5. Compression Process

[0426] After completing step 4 above, the mixed material was compressed into a tablet form having an average mass of 670 or 662 mg ± 2%, an individual mass of 670 or 662 mg ± 5%, an individual thickness of 5.0 to 5.6 mm, an individual strength of 11 to 26 kP, and a disintegration time of less than 30 minutes in purified water.

[0427] The compositions of Manufacturing Examples 9 and 10 above are as shown in Table 5 below.

[0428] Preparation Example 9 Preparation Example 10 Active Ingredient Compound 1400 mg 400 mg Filler Microcrystalline Cellulose (Step 1) 150 mg 150 mg Lactose Monohydrate (Step 1) 60 mg 60 mg Disintegrant Croscarmellose Sodium (Step 1) 20 mg 20 mg Croscarmellose Sodium (Step 4) 5 mg 5 mg Binder Hypromellose 25 mg Hydroxypropyl Cellulose 17 mg Solvent Purified Water (200 mg) (200 mg) Lubricant Magnesium Stearate 10 mg 10 mg Total Weight 670 mg 662 mg

[0429]

[0430] Comparative Example 1. Preparation of a placebo composition

[0431] A placebo composition (Comparative Example 1) was prepared by carrying out the same process as in Preparation Example 1, except that Compound 1 was replaced with an equal amount of microcrystalline cellulose or lactose.

[0432] The composition of Comparative Example 1 is as shown in Table 6 below.

[0433] Comparative Example 1 Active Ingredient Compound 1-Filler Microcrystalline cellulose (Step 1) 192.5 mg Microcrystalline cellulose (Step 4) 15 mg Lactose monohydrate (Step 1) 87.5 mg Lactose monohydrate (Step 4) 5 mg Disintegrant Carboxymethylcellulose calcium (Step 1) 10 mg Carboxymethylcellulose calcium (Step 4) 10 mg Crosscarmellose sodium-Binder Povidone 20 mg Solvent Purified water 0.04 mL Lubricant Magnesium stearate 6 mg Coating agent Hypromellose 11.5 mg Polyethylene glycol 6000 1 mg Talc 1 mg Titanium oxide 1 mg Solvent Ethanol 0.09 mL Methylene chloride 0.09 mL Purified water- Color Sunset Yellow FCF 0.0042 mg Total weight 360.5 mg

[0434]

[0435] Comparative Example 2. Preparation of a placebo composition

[0436] Microcrystalline cellulose, lactose monohydrate, carboxymethylcellulose calcium, and povidone were placed in a mixer and mixed for 5 minutes, then compressed to have an average mass of 705 mg ± 2%, an individual mass of 705 mg ± 4%, an individual thickness of 5.6 to 6.2 mm, an individual strength of 3 to 9 kP, and a disintegration time of less than 30 minutes under purified water.

[0437] Subsequently, a placebo composition (Comparative Example 2) was prepared by coating a tablet that had undergone a compression process in a coating solution mixed with hypromellose, polyethyleneglycol 6000, talc, titanium oxide, and yellow 5 pigment.

[0438] The composition of Comparative Example 2 is as shown in Table 7 below.

[0439] Comparative Example 2 Active Ingredients Compound 1-Filler Microcrystalline cellulose (Step 1) 153 mg Lactose monohydrate (Step 1) 460 mg Disintegrant Carboxymethylcellulose calcium (Step 1) 40 mg Binder Povidone 40 mg Lubricant Magnesium stearate 12 mg Coating agent Hypromellose 23 mg Polyethylene glycol 6000 2 mg Talc 2 mg Titanium oxide 2 mg Solvent Purification Color: Orange No. 5 0.084 mg Total Weight 734 mg

[0440]

[0441] Comparative Example 3. Preparation of a placebo composition

[0442] Microcrystalline cellulose, lactose monohydrate, carboxymethylcellulose calcium, and povidone were placed in a mixer and mixed, and then compressed to have an average mass of 690 mg ± 2%, an individual mass of 690 mg ± 4%, an individual thickness of 5.0 to 5.6 mm, an individual strength of 11 to 26 kP, and a disintegration time of less than 30 minutes in purified water to prepare a placebo composition (Comparative Example 3). Subsequently, the tablets that underwent the above compression process were coated according to the coating process of Preparation Example 2.

[0443] The composition of Comparative Example 3 is as shown in Table 8 below.

[0444] Comparative Example 3 Active Ingredient Compound 1-Filler: Microcrystalline cellulose (Step 1) 150 mg Lactose monohydrate (Step 1) 460 mg Disintegrant: Croscarmellose sodium (Step 1) 30 mg Binder: Povidone 40 mg Lubricant: Magnesium stearate 10 mg Coating Agent: Opadry 321A18002525 mg Solvent: Purified water (141 mg) Total Weight: 715 mg

[0445]

[0446] Examples

[0447] Example 1. Confirmation of characteristics of a pharmaceutical composition

[0448] The above Manufacturing Examples 1 to 10 are compositions in the form of rectangular film-coated tablets, and it was confirmed that they satisfy the evaluation criteria for finished pharmaceutical products (content, purity, uniformity, dissolution rate, and stability).

[0449] Specifically, it was confirmed that the same compound is included by confirming in HPLC or UV spectrum analysis that the peak positions of the standard solution for inspection and the composition to be inspected are identical and the peak area is 90 to 110% of that of the standard solution for inspection.

[0450] In addition, the purity test confirmed that the impurity content was less than the evaluation standard of 2%, and the formulation uniformity test confirmed that it was 1.3% to 3.4%, which is much lower than the standard of less than 15.0%.

[0451] In the dissolution test, it was confirmed that at least 75% of the composition was dissolved within 30 minutes. Specifically, it was confirmed that at least 89.9% and an average of 91.9% were dissolved.

[0452] In addition, it was confirmed that the composition is a highly stable composition by confirming that it can be stored for 12 to 60 months or more under long-term storage conditions at 25°C and 60% relative humidity, and for 6 months or more under accelerated storage conditions at 40°C and 75% relative humidity.

[0453]

[0454] Example 2. Analysis of dissolution characteristics of a pharmaceutical composition

[0455] A comparative elution test was performed for each of the above Preparation Examples 1 to 5, Preparation Example 9, and Preparation Example 10.

[0456] Specifically, each preparation example (12 tablets per preparation example) was added to 900 mL of water, and the dissolution rate over time was checked while mixing at 50 rpm.

[0457] As a result, the dissolution rates after 5, 10, 15, 30, and 45 minutes based on the time of addition were confirmed to be 12, 36, 62, 89, and 92% for Preparation Example 1, respectively; 42, 72, 85, 92, and 93% for Preparation Example 2, respectively; 22, 45, 69, 92, and 94% for Preparation Example 3, respectively; 20, 42, 59, 88, and 95% for Preparation Example 4, respectively; 10, 37, 55, 83, and 97% for Preparation Example 5, respectively; 24, 53, 73, 96, and 99% for Preparation Example 9, respectively; and 33, 49, 65, 91, and 99% for Preparation Example 10, respectively.

Claims

1. An oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof; One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and A pharmaceutical composition comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose potassium, sodium starch glycolate, crospovidone, starch, and gelatinized starch: [Chemical Formula 1] (In the above chemical formula 1, The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and; The above n is an integer from 0 to 2; The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures; ; The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen; The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H; The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl; The above m is one integer from 1 to 6; The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is; The above R 41 It is a (C1-C6) alkyl.

2. A pharmaceutical composition according to claim 1, wherein R is hydrogen.

3. A pharmaceutical composition according to claim 1, wherein Q is -OH.

4. A pharmaceutical composition according to Claim 1, wherein the oxazolidinone derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof is a compound represented by Formula 2 or a pharmaceutically acceptable salt thereof: [Chemical Formula 2] .

5. A pharmaceutical composition according to claim 1, wherein the binder is one or more selected from the group consisting of povidone, hypromellose, and hydroxypropylcellulose.

6. A pharmaceutical composition according to claim 1, wherein the binder is included in an amount of 4 to 45 weight percent relative to the total weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition according to claim 1, wherein the binder is included in an amount of 2 to 8 weight percent relative to the total weight of the pharmaceutical composition.

8. A pharmaceutical composition according to claim 1, wherein the disintegrant is one or more selected from the group consisting of sodium croscarmellose and calcium carboxymethylcellulose.

9. A pharmaceutical composition according to claim 1, wherein the disintegrant is contained in an amount of 5 to 45 weight percent relative to the weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition according to claim 1, wherein the disintegrant is included in an amount of 3 to 10 weight% relative to the total weight of the pharmaceutical composition.

11. A pharmaceutical composition according to claim 1, wherein the binder and the disintegrant are included in a weight ratio of 1:0.5 to 1.

8.

12. A pharmaceutical composition according to claim 1, further comprising one or more lubricants selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, tartaric acid, sodium lauryl sulfate, polyethylene glycol, and sodium stearyl fumarate.

13. A pharmaceutical composition according to claim 12, wherein the lubricant is magnesium stearate.

14. A pharmaceutical composition according to claim 12, wherein the lubricant is contained in an amount of 2 to 12 weight percent relative to the weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition according to claim 12, wherein the lubricant is included in an amount of 1 to 3 weight percent relative to the total weight of the pharmaceutical composition.

16. A pharmaceutical composition according to claim 1, further comprising one or more fillers selected from the group consisting of microcrystalline cellulose, lactose monohydrate, lactose, mannitol, sorbitol, glucose, sucrose, maltose, calcium phosphate, and dextrin.

17. A pharmaceutical composition according to claim 16, wherein the filler is one or more selected from the group consisting of microcrystalline cellulose, lactose monohydrate, and lactose.

18. A pharmaceutical composition according to claim 16, wherein the filler is included in an amount of 45 to 500 weight% relative to the weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof.

19. A pharmaceutical composition according to claim 16, wherein the filler is included in an amount of 25 to 70 weight% relative to the total weight of the pharmaceutical composition.

20. A pharmaceutical composition according to claim 1, further comprising one or more coating agents selected from the group consisting of hypromellose, polyethylene glycol, ethylene glycol, vinyl alcohol graft copolymer, talc, titanium oxide, titanium dioxide, glyceryl monocaprylocaprate Type 1, and polyvinyl alcohol.

21. A pharmaceutical composition according to claim 20, wherein the coating agent is included in an amount of 5 to 30 weight percent based on the weight of the oxazolidinone derivative or a pharmaceutically acceptable salt thereof.

22. A pharmaceutical composition according to claim 20, wherein the coating agent is included in an amount of 3 to 5 weight percent relative to the total weight of the pharmaceutical composition.

23. The pharmaceutical composition of Claim 1, wherein the pharmaceutical composition is an immediate-release formulation.

24. A pharmaceutical composition according to claim 1, wherein 10 to 50 weight percent of the total weight of the pharmaceutical composition is dissolved within 5 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution.

25. The pharmaceutical composition of claim 1, wherein 30 to 80 weight percent of the total weight of the pharmaceutical composition is dissolved within 10 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution.

26. A pharmaceutical composition according to claim 1, wherein 55 to 90 weight percent of the total weight of the pharmaceutical composition is dissolved within 15 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution.

27. The pharmaceutical composition of claim 1, wherein 80 to 99 weight percent of the total weight of the pharmaceutical composition is dissolved within 30 minutes in a solvent selected from the group consisting of water, blood, physiological saline, and buffer solution.

28. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a formulation for oral administration.

29. A pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a tablet.

30. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is for the prevention or treatment of bacteria-mediated diseases.

31. A step of obtaining a first mixture by mixing an oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof and a disintegrant; A step of obtaining a second mixture by mixing the first mixture and the binder above. The method includes the step of mixing the second mixture and the disintegrant to obtain a third mixture; The above binder is one or more selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose; A method for preparing a pharmaceutical composition in which the above-mentioned disintegrant is one or more selected from the group consisting of sodium croscarmellose, calcium carboxymethylcellulose, sodium starch glycolate, crospovidone, starch, and pregelatinized starch: [Chemical Formula 1] (In the above chemical formula 1, The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and; The above n is an integer from 0 to 2; The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures: ; The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen; The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl or -C(=O)H; The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl; The above m is one integer from 1 to 6; The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is; The above R 41 It is a (C1-C6) alkyl.

32. A method for preparing a pharmaceutical composition according to claim 31, wherein, in the step of obtaining the first mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the disintegrant are mixed in a weight ratio of 1:0.05 to 0.

25.

33. A method for preparing a pharmaceutical composition according to claim 31, wherein, in the step of obtaining the first mixture, one or more fillers selected from the group consisting of microcrystalline cellulose, lactose monohydrate, lactose, mannitol, sorbitol, glucose, sucrose, maltose, calcium phosphate, and dextrin are further mixed.

34. A method for preparing a pharmaceutical composition according to claim 33, wherein, in the step of obtaining the first mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the filler are mixed in a weight ratio of 1:0.2 to 5.

35. A method for preparing a pharmaceutical composition according to claim 31, wherein, in the step of obtaining the second mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the binder are mixed in a weight ratio of 1:0.04 to 0.

5.

36. A method for preparing a pharmaceutical composition according to claim 31, further comprising the step of sieving the second mixture prior to the step of obtaining the third mixture.

37. A method for preparing a pharmaceutical composition according to claim 36, further comprising the step of drying the filtered second mixture prior to the step of obtaining the third mixture.

38. A method for preparing a pharmaceutical composition according to claim 37, further comprising the step of milling the dried second mixture prior to the step of obtaining the third mixture.

39. A method for preparing a pharmaceutical composition according to claim 31, wherein, in the step of obtaining the third mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the disintegrant are mixed in a weight ratio of 1:0.01 to 0.

3.

40. A method for preparing a pharmaceutical composition according to claim 31, wherein, in the step of obtaining the third mixture, one or more fillers selected from the group consisting of microcrystalline cellulose, lactose monohydrate, lactose, mannitol, sorbitol, glucose, sucrose, maltose, calcium phosphate, and dextrin are further mixed.

41. A method for preparing a pharmaceutical composition according to claim 40, wherein, in the step of obtaining the third mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the filler are mixed in a weight ratio of 1:0.05 to 0.

5.

42. A method for preparing a pharmaceutical composition according to claim 31, further comprising the step of mixing the third mixture with one or more lubricants selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, tartaric acid, sodium lauryl sulfate, polyethylene glycol, and sodium stearyl fumarate to obtain a fourth mixture.

43. A method for preparing a pharmaceutical composition according to claim 42, wherein, in the step of obtaining the fourth mixture, the oxazolidinone derivative or a pharmaceutically acceptable salt thereof and the lubricant are mixed in a weight ratio of 1:0.01 to 0.

15.

44. A method for preparing a pharmaceutical composition according to claim 42, further comprising, after the step of obtaining the fourth mixture, the step of pressing the fourth mixture to obtain a solid formulation.

45. A method for preparing a pharmaceutical composition according to claim 44, further comprising, after the step of obtaining the solid formulation, the step of coating the solid formulation with one or more coating agents selected from the group consisting of hypromellose, polyethylene glycol, ethylene glycol, vinyl alcohol graft copolymer, talc, titanium oxide, titanium dioxide, type 1 glycerol monocaprylcaprate, and polyvinyl alcohol.

46. ​​A method for preparing a pharmaceutical composition according to claim 45, wherein the coating step is performed under an air supply temperature of 40 to 75°C and an exhaust temperature of 40 to 65°C.

47. An oxazolidinone derivative represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof; One or more binders selected from the group consisting of povidone, hypromellose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, gelatin, and hydroxypropylcellulose, and Antibiotic composition comprising one or more disintegrants selected from the group consisting of croscarmellose sodium, carboxymethylcellulose calcium, starch glycolate sodium, crospovidone, starch, and pregelatinized starch: [Chemical Formula 1] (In the above chemical formula 1, The above X is a chemical bond, -(CH2)n- or -(CH2)nC(=O)- and; The above n is an integer from 0 to 2; The above R is hydrogen or a pentagonal or hexaagonal heteroaryl selected from the following structures; ; The above R1 to R 25 are independently hydrogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, -OH, -NR 31 R 32 , -C(=O)R 33 , -(CH2) m OH, -C=NOH, -CN, -NO2 or halogen; The above R 31 and R 32 are independently hydrogen, (C1-C6) alkyl, or -C(=O)H; The above R 33 It is hydrogen, -OH, -NH2, or (C1-C6) alkyl; The above m is one integer from 1 to 6; The above Q is -OH, -NHC(=O)R 41 or -NHC(=O)OR 41 is; The above R 41 It is a (C1-C6) alkyl.

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