228 results about "Linezolid" patented technology

The present invention relates to solid oral dosage forms of linezolid polymorphic Form III with reproducible dissolution profile and processes for their preparation. The solid dosage form includes linezolid Form III, one or more of means to reduce the gelling tendency of linezolid form III, and one or more of pharmaceutically acceptable excipients.

The invention relates to a synthetic method for linezolid, which dissolves a 3-fluoro-4- morpholinyl laniline and an N-2(R)-epoxy acetamide in an organic solvent to react for 10 to 30 hours in a temperature of 20 to 100 DEG C, and acquires an N-{2(R)-2-[(3-fluoro-4 morpholine-4-base phenyl) amino]-2-hydroxy ethyl}; then an acquired compound and a carbonylation agent are dissolved in a halohydrocarbon organic solvent and reacted for 0.5 to 5 hours in a temperature of 0-50 DEG C under the catalysis of a base catalyst, thereby acquiring the linezolid. The method of the invention uses an ordinary reagent and normal plant conditions in industry, the reaction condition is mild and the steps are simple.

The present invention provides a novel process for preparation of 5-aminomethyl substituted oxazolidinones, key intermediates for oxazolidinone antibacterials including linezolid. Thus linezolid is prepared by a) reacting 3-fluoro-4-morpholinyl aniline with R-epichlorohydrin; b) subjecting N-[3-Chloro-2-(R)-hydroxypropyl]-3-fluoro-4-morpholinyl aniline produced above to carbonylation; c) reacting (5R)-5-(chloromethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone produced above with potassium phthalinide; d) reacting (S)-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]phthalimide produced above with hydrazine hydrate; and e) reacting S-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazo-lidinyl]methyl]amine produced above with acetic anhydride to produce linezolid.

The invention relates to a preparation method of linezolid and a preparation thereof, in particular to a preparation method of a linezolid raw material and a freeze-dried powder injection thereof. The preparation method mainly comprises the following steps: (1) synthesizing 2(S)-1-amino-3-chloro-2-propanol hydrochloride; (2) synthesizing (S)-N-[2-acetoxyl-3-chloropropyl] acetamide; (3) synthesizing 3-fluoro-4-morpholinyl nitrobenzene; (4) synthesizing N-carbobenzoxy-3-fluoro-4-morpholinyl aniline; (5) synthesizing the linezolid; and (6) preparing the linezolid preparation. The freeze-dried powder injection of the linezolid for injection, which is prepared by the invention, effectively improves the stability of medicines so that the medicines have longer shelf life, can be transported more conveniently and are more favorable for clinical applications. Moreover, the method of the invention for preparing the raw material linezolid and the freeze-dried powder injection thereof is simple and effective and is suitable for large-scale industrial production.

The present invention provides compositions and methods for prevention, amelioration and treatment of gram positive bacteria, particularly Staphylococcal bacteria, with combinations of lysin, particularly Streptococcal lysin, particularly the lysin PlySs2, and one or more antibiotic, including daptomycin, vancomycin, oxacillin, linezolid, or related antibiotic(s).

The present invention provides a novel process for preparation of 5 aminomethyl substituted oxazolidinones, key intermediates for oxazolidinone antibacterials including linezolid. Thus, the key intermediate of linezolid is prepared by a) reacting N-[3-Chloro-2-(R)-hydroxypropyl]-3-fluoro-4-morpholinyl aniline with potassium phthalimide; b) subjecting N-[3-pthalimido-2-(R)-hydroxypropyl]-3-fluoro-4-(morpholinyl) aniline produced in the above step to carbonylation; and c) reacting (S)-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidiriyl]methyl]phthalimide produced in the above step with hydrazine hydrate to produce (S)-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine.

The invention relates to a preparation method for linezolid, which comprises the following steps of: carrying out condensation reaction on N-benzyloxyl hydroxyl-3-fluoro-4-morpholinyl aniline and (S)-N-[2-acetoxyl-3-chloropropyl] acetamide in a solvent and purifying to obtain linezolid, wherein a condensating agent is lithium tert-butoxide, the solvent is a mixed solvent of dimethyl formamide, methanol and dichlormethane in volume ratio of (7-9):(0.8-1.2):(75-85). The preparation method has the advantages of simple operation, shorter reaction time and high yield, and is suitable for industrial production.

The present invention provides a novel process for preparation of 5 aminomethyl substituted oxazolidinones, key intermediates for oxazolidinone antibacterials including linezolid. Thus, the key intermediate of linezolid is prepared by a) reacting N-[3-Chloro-2-(R)-hydroxypropyl]-3-fluoro-4-morpholinyl aniline with potassium phthalimide; b) subjecting N-[3-pthalimido-2-(R)-hydroxypropyl]-3-fluoro-4-(morpholinyl) aniline produced in the above step to carbonylation; and c) reacting (S)-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidiriyl]methyl]phthalimide produced in the above step with hydrazine hydrate to produce (S)-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine.

The present invention provides a novel process for preparation of 5-aminomethyl substituted oxazolidinones, key intermediates for oxazolidinone antibacterials including linezolid. Thus linezolid is prepared by a) reacting 3-fluoro-4-morpholinyl aniline with R-epichlorohydrin; b) subjecting N-[3-Chloro-2-(R)-hydroxypropyl]-3-fluoro-4-morpholinyl aniline produced above to carbonylation; c) reacting (5R)-5-(chloromethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone produced above with potassium phthalinide; d) reacting (S)-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]phthalimide produced above with hydrazine hydrate; and e) reacting S-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazo-lidinyl]methyl]amine produced above with acetic anhydride to produce linezolid.

The invention discloses a preparation method of IV crystal linezolid tablets having high drug loading capacity and capable of quickly dissolving. The preparation method comprises the following steps of preprocessing, premixing, mixing, granulating, drying, arranging granulates, centrally controlling, tabletting and coating. According to the preparation method, corn starch and silica are matched with each other, therefore, the tablets with hardness more than 30kg can be quickly cracked, and the in-vitro dissolution similarity ranging from 50 to 100 with respect to a referred product, as well as high drug loading capacity, can be realized.

The invention discloses an evaporation crystallization process for linezolid with crystal form I. The method comprises the steps of: dissolving 1 weight part of linezolid in 3 to 5 weight parts of alcohol solvents, evaporating 60 to 70 weight percent of alcohol solvents at the temperature of between 70 and 100 DEG C, inducing crystal nuclei of the linezolid with crystal form I in a boiling state,reducing the temperature by 10 to 20 DEG C, adding the evaporated alcohol solvents again, precipitating crystals, filtering, washing a filter cake by using n-heptane, and performing vacuum-drying at the temperature of between 40 and 50 DEG C and under the pressure of -0.08 to -0.09 MPa to obtain the linezolid with crystal form I. In the evaporation process, the using amount of the solvents is small, the evaporation speed is high, evaporated liquor does not contain crystals, and the evaporated liquor can be directly recycled; and the linezolid is not decomposed and deteriorated, yield is high and the quality is good.

The invention provides ophthalmic bacterial-infection resisting medicine for external use. Linezolid is adopted as medicative raw materials to prepare eye drops, ophthalmic gel and eye ointments. The content of the linezolid in every 100 parts by weight of a medicament is within 0.1 to 1.0 parts by weight. The medicine is for external use at partial positions of eyes, and has good intraocular penetrability and mild toxic as well as side effects; moreover, the medicine is suitable for treating as well as preventing bacterial infection at partial positions of the eyes, including diseases of conjunctivitis, keratitis, keratohelcosis, iritis, ocular traumas, chemical injuries, ophthalmic postoperative infections and the like.

The present invention provides improved methods of converting R-N-(4-morpholiyl-3-fluorophenyl)-2-oxo-5-oxazolidinyl-methyl azide (III) to the intermediate S-N-(4-morpholinyl-3-fluorophenyl)-2-oxo-5-oxazolidinyl-methyl amine (II) that involve the production of fewer by-products than previous methods. The amine (II) may then be converted into linezolid (I) of high chemical purity with respect to the inactive R-enantiomer and bis-linezolid (IV), and is in high yield, without the need for tedious, complicated purification steps, such as chromatography.

The invention provides a method for preparing Linezolid. The preparation method has the advantages of few total reaction steps of the synthetic route, high yield, mild reaction of each step of the synthesis, no need of special reagent and device, and simple operation, and is suitable for large scale industrial production. High-purity of Linezolid can be prepared by the method, and medicinal requirements can be satisfied.

The invention provides a new crystal form V of an oxazolidinone antibacterial, namely (S)-N-[[3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methyl]acetamide (linezolid). Characteristic absorption peaks appear on the crystal X-ray powder diffraction pattern of the crystal at the following reflection angle 2 theta: 7.40 degrees, 13.45 degrees, 14.64 degrees, 17.92 degrees, 19.80 degrees, 21.07 degrees, 22.10 degrees, 25.42 degrees, 27.65 degrees, 28.35 degrees and 29.65+ / -0.2 degrees. The invention also provides a preparation method and application of the material in the new crystal form and a pharmaceutical composite containing the material in the crystal form. The material in the crystal form has the advantages of better stability, simple preparation process and lower preparation cost, and the industrial production of the material in the crystal form can be realized.

The present invention provides compositions and methods for prevention, amelioration and treatment of gram positive bacteria, particularly Staphylococcal bacteria, with combinations of lysin, particularly Streptococcal lysin, particularly the lysin PlySs2, and one or more antibiotic, including daptomycin, vancomycin, oxacillin, linezolid, or related antibiotic(s).

The invention relates to a tablet containing a linezolid crystal form III. The tablet contains 67.0-75.0wt% of linezolid, 2.0-4.8wt% of lactose, 9.0-18.0wt% of microcrystalline cellulose as well as disintegrating agent, binding agent, lubricant and other medicinal excipients, wherein preferably, the tablet contains 67.0-75.0wt% of linezolid, 2.0-4.8wt% of lactose, 9.0-18.0wt% of microcrystalline cellulose, 2.0-10.0wt% of disintegrating agent, 1.2-4.0wt% of binding agent and 0.3-2.0wt% of lubricant. The tablet containing the linezolid crystal form III of the prescription, in an extremely limited additive adding range, guarantees characteristics of good compressibility, excellent formability and rapid dissolution.

The invention provides a use of an oxazolidinone compound shown in the formula I in preparation of a drug, a disinfectant or a daily chemical article for preventing or inhibiting bacterial biomembrane formation or removing a bacterial biofilm. The oxazolidinone compound can effectively prevent or inhibit bacterial biofilm formation or removing a bacterial biofilm, can effectively reduce biomass and viable count of a biofilm, has biofilm resistance activity obviously superior to that of a classical drug linezolid, and provides a better choice for treatment or prevention of biofilm-caused infection.

The invention provides a preparation method of linezolid which is an antimicrobial medicament with a brand-new structure and has an obvious effect in the aspects of treating drug-resistant gram-positive bacteria and Mycobacterium tuberculosis infections. The invention relates to a synthesis method of linezolid. The method comprises the following steps: carrying out a reaction on S-epichlorohydrinand sodium azide to obtain 1-azido-3-chloro-2-propanol; cyclizing 1-azido-3-chloro-2-propanol with N-(3-fluoro-4-morpholinophenyl) urethane; and finally, reducing and acetylizing to obtain the linezolid. The method provided by the invention has the advantages of cheap-price and available raw materials, simple technology process and high product yield, provides a new way for industrial production of linezolid.

The invention discloses a preparation method of linezolid. The method comprises reacting 3,4-difluoronitrobenzene to generate 3-fluoro-4-morpholine nitrobenzene, and then adding a small amount of catalyst Pd / C, In the case of hydrogen, 3-fluoro-4-morpholine aniline is obtained, which does not undergo separation and purification on a silica gel column, and reacts to generate N-Cbz-3-fluoro-4-morpholine aniline, and then reacts with the intermediate 3-chloro- 2-Acetoxyacetylpropylamide reacts to form linezolid. The preparation method of the invention not only reduces numerous purification steps in the reaction, but also reduces the amount of catalyst used, thereby making the preparation of linezolid more effective and more environmentally friendly.

Linezolid salts, useful as such and as intermediates in a process for the preparation of novel and known crystalline linezolid forms, in particular known as Form III.

The present invention relates to novel crystalline forms of the linezolid intermediate S—N-(4-morpholinyl-3-fluorophenyl)-2-oxo-5-oxazolidinyl-methyl amine referred to herein as Form A, Form B, and Form C.

The invention discloses a linezolid-containing anti-infection pharmaceutical composition and a preparation method thereof. The pharmaceutical composition contains 1.0-5.0% (g / ml) of linezolid and is composed of an ethosome drug-loading system and a hydrogel system; and the pharmaceutical composition can be prepared into a linezolid-ethosome gel spray, and can be externally applied to anti-infection treatment.

The invention discloses a suspension crystallization method for preparing a crystal form I of linezolid. The method comprises the following steps of: mixing 1 to 10 weight part of water and 1 weight part of linezolid, heating to the temperature of between 95 and 105DEG C to obtain suspension, crystallizing at the temperature of between 70 and 100DEG C, filtering at the temperature of between 0 and 90DEG C, and performing vacuum drying on a filter cake at the temperature of between 30 and 90DEG C to obtain the crystal form I of the linezolid. The method has the advantages that: water is taken as a suspension solvent, organic solvents are not used at all, the method is green, safe, environment-friendly and pollution-free, the product yield is high, the filter cake is not required to be washed, the filtered mother solution can be repeatedly used, the volume of the mother solution cannot be increased due to reuse, the energy consumption in the production process is obviously reduced, and clean production can be realized.

The invention relates to a method for preparing linezolid. The method comprises the following steps of: reacting 3-fluorine-4-morpholinyl bromobenzene used as a raw material, with a chiral oxazolidinone compound in the presence of a catalyst, so as to directly obtain the linezolid, or to obtain the linezolid after conversion. Compared with the existing method for synthesizing linezolid, the method disclosed by the invention is simple in route, convenient to operate, slight in pollution and stable in yield.

The invention relates to a method for preparing linezolid. The method is characterized by reacting 3-fluoro-4-morpholinyl bromobenzene as raw material with a chiral oxazolidinone compound under the action of a catalyst to obtain linezolid. Compared with the prior art, the inventive method has the advantages of simple synthesis path, simple operation, less pollution and stable yield.

The invention discloses a Porphyromonas gingivalis culture medium for tartar specimens and a preparation method thereof. The invention is characterized in that every 1000ml of culture medium contains malt extract, egg white, hemin solution, vitamin K1 ethanol solution, magnesium citrate, agar, synercid, telithromycin, linezolid, asparagine and the balance of distilled water. The preparation method of the optimal formula comprises the following steps: dissolving the malt extract, egg white, hemin, agar, magnesium citrate, calcium citrate tetrahydrate, synercid, garlic press juice and L-cysteine in a rhizoma polygonati boiling solution, evenly mixing, adding water to the constant volume, sterilizing and packaging. Compared with the prior art, the culture medium has the characteristics of high detection reliability and high Porphyromonas gingivalis separation rate.

The present invention relates to novel phenyl oxazolidinone compounds of formula I, their pharmaceutically acceptable analogs, tautomeric forms, stereoisomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also relates to the processes for the synthesis of novel compounds of formula I or their pharmaceutically acceptable analogs, tautomeric forms, stereoisomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The present invention also provides pharmaceutical compositions comprising novel compounds of formula I and methods of using them. The compounds of the present invention are useful as antimicrobial agents, effective against a number of aerobic and / or anaerobic Gram positive and / or Gram negative pathogens such as multi drug resistant species of Staphylococcus, Streptococcus, Enterococcus, Bacterioides, Clostridia, H. influenza, Moraxella, acid-fast organisms such as Mycobacterium tuberculosis as well as Linezolid resistant species of Staphylococcus and Enterococcus.

The invention belongs to the field of pharmaceutic preparation, and specifically a linezolid oral suspension and a preparation method thereof. The linezolid oral suspension comprises the following components by weight: 0.5-2.0 parts of linezolid, 0.5-5.0 parts of sodium carboxymethyl cellulose, 0.05-0.5 part of polysorbate 80, 0.15-0.20 part of sodium citrate, 0.08-0.10 part of citric acid, 0.22-0.28 part of a preservative, 22-28 parts of sweetener, 1.2-1.8 parts of a correctant and an aqueous medium. The present invention fills the market blank of only containing tablet or injection, and provides a novel dosage form choice. The linezolid oral suspension product has good quality, can be accurately divided into the dosage based on body weight, and is easy to swallow. The preparation process is simple, feasible and reproducible, and can consistently produce linezolid oral suspension with quality meeting the requirements.