625 results about "Florfenicol" patented technology

The present invention is directed to a new process of preparing highly pure Florfenicol. The invention is further directed to new oxazolidine derivatives useful in making Florfenicol and processes of making these derivatives. Examples of such intermediates include (4R,5R)-3-acetyl-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine; and (4S,5R)-3-acetyl-2,2-dimethyl-4-fluoromethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine.

The present invention discloses phosphate esters of florfenicol (prodrugs) and florfenicol analogs having superior water solubility that are hydrolyzed to florfenicol or the respective florfenicol analog in vivo, upon administration to an animal.

Novel florfenicol compounds having the chemical structure:

• • or a pharmaceutically-acceptable salt thereof or a solvate thereof,or prodrug thereof, wherein R¹ is CHCl₂, CHClF, CHF₂, CHBrCl, CH₃, CH₂N₃, CH₂CN, CH(R²)NH₂ or CH X¹X²; where R² is H, CH₃ or CH₂OH, and X¹ and X² are independently selected halogens; and R³ is CH₂Cl, CH₂F, CHF₂, CHCl₂ or CH₂OH are disclosed. The compounds are useful for the treatment and/or prevention of bacterial infections in a broad range of patients such as, without limitation, birds, fish, shellfish and mammals.

The invention relates to a method for analyzing (1R, 2R)-2-amino-1-(4-(methylsulfonyl)-phenyl)-1,3-propylene glycol as an important intermediate of florfenicol, which is chloramphenicol spectrum antibiotic special for animals. The method comprises the following steps of: performing a reaction of methylsulfonyl benzaldehyde and nitro alcohol at 0-40 DEG C in the presence of a chiral catalyst to obtain (1R, 2R)-2-nitro-1-(4-(methylsulfonyl)-phenyl)-1,3-propylene glycol; and reducing the (1R, 2R)-2-nitro-1-(4-(methylsulfonyl)-phenyl)-1,3-propylene glycol through hydrogen to obtain the intermediate. In the invention, the compound (1R, 2R)-2-amino-1-(4-(methylsulfonyl)-phenyl)-1,3-propylene glycol with a high e.e. value is obtained by adopting the chiral catalyst, and the compound has the advantages of strong reaction selectivity, high productivity, simple process, low cost, easy preparation of raw materials and low price, is suitable for industrial production, avoids chiral separation frequently used in industry at present and saves the raw materials and the cost. The compound (1R, 2R)-2-amino-1-(4-(methylsulfonyl)-phenyl)-1,3-propylene glycol is used for preparing florfenicol and can reduce the preparation cost.

The invention discloses a synthesis method of synthesizing florfenicol. The synthesis method comprises the following steps: L-threo-(p-(methylsylfonyl) phenyl) serine ethyl ester which is used as raw material is processed by the protection by a protecting group, configurational transition, hydrolyzation, acetylation, re-protection, deoxidation, fluorination, and pre-hydrolyzation, so that the florfenicol is obtained, wherein, the protecting group R is one of benzoyl chloride, phthalic anhydride, cyanophenyl, and allyl compounds; the configurational transition is performed when sodium alcoholate or sodium methoxide exists. The raw material which is used in the method is a byproduct which is generated during the process of preparing thiamphenicol, is easy to get in the market, and is inexpensive; the technological operation is simple, the cost is low, the yield rate is high, and the synthesis method has industrialized value.

The invention relates to a method for producing florfenicol soluble powder. The method comprises the following technical steps of: 1, including florfenicol and 2-hydroxypropyl-beta-cyclodextrin; and 2, performing spray drying on included solution by a spray drying tower. By combining grinding inclusion and spray drying process, the production efficiency and the yield are high; the solubility of the prepared florfenicol-included powder is increased to be 263mg/ml (soluble) from original 13mg/ml (slight soluble) and enlarged by 20 times; and the product can be directly dissolved in water and diseases of animals can be treated by drinking the water.

The invention relates to a cyclodextrin-included florfenicol quick-release water-soluble powder preparation and a preparation method thereof. The preparation is prepared by stirring florfenicol, cyclodextrin and water at a uniform speed and including by using an inclusion technology. The preparation can be directly dissolved in water to be taken by livestock, and has the characteristics of high medicine dissolution rate, high dissolubility, high bioavailability, good absorption and the like; and the medicine (florfenicol) is included in a carrier material, the bitterness of the florfenicol can be masked, and the intake or drinking of animals cannot be influenced by the bitterness of the medicine.

The invention discloses a florfenicol composition with high bioavailability. The florfenicol composition is prepared from, by weight, 1-5 parts of florfenicol, 2-50 parts of beta-cyclodextrin and 5-10 parts of absorption promoter. The florfenicol composition has the advantages that the florfenicol composition with high bioavailability is obtained by screening through a large amount of experiments, the absorption promoter is added on the basis of florfenicol cyclodextrin inclusion complex, the defect that florfenicol is difficult to dissolve in water is overcome while the oral bioavailability of the florfenicol can be increased greatly. A preparation method of the florfenicol composition is reasonable in process design, high in operability and capable of achieving industrial production.

The invention discloses a method for preparing solid florfenicol dispersion, and relates to the field of animal medicine. The solid florfenicol dispersion is uniformly and sequentially prepared from the following components in parts by weight: 15 to 25 parts of florfenicol (sieved with a sieve of 80 meshes), 15 to 25 parts of poloxamer, and 50 to 70 parts of polyethylene glycol-4000. The preparation method comprises the following steps of: (1) weighing 15 to 25 parts of florfenicol (sieved with the sieve of 80 meshes), 15 to 25 parts of poloxamer and 50 to 70 parts of polyethylene glycol-4000 by weight; (2) heating and melting the poloxamer and the polyethylene glycol-4000, stirring for 3 to 5 minutes till the mixture is uniform, adding the florfenicol, and stirring uniformly; and (3) quickly cooling the mixture obtained in the (2) to the temperature of 10 DEG C below zero, crushing, and thus obtaining the solid florfenicol dispersion. The preparation process is simple, and the dissolubility of the florfenicol is remarkably improved and is about 2 times that of a common florfenicol preparation (soluble powder or oral liquid).

Disclosed is a method to prepare florfenicol sodium succinate. Florfenicol reacts with succinic anhydride in organic solvent with triethylamine as activator under 10-15 DEG C to produce florfenicol ester succinate which then reacts with sodium hydroxide in organic solvent under 10-15 DEG C, producing florfenicol sodium succinate which is soluble in water. The mol ratio of the materials of florfenicol: triethylamine:succinic anhydride is 1:2-4:1.5-3. Florfenicol sodium succinate preparation can be made into injection, aqueous solution and lyophilized powder and can be used for disease prevention and treatment on animals.

The invention provides a high-efficiency, rapid and safe compound pharmaceutical composition for curing virus diseases of animals and a preparation method thereof. The compound pharmaceutical composition comprises the following components of forsythia fruit, isatis root, bamboo leaf, scutellaria root, honeysuckle flower, isatis leaf, milkvetch root, longspur epimedium, glossy privet fruit, dried rehmannia root, red sage root, chuanxiong rhizome, dark plum, peppergrass, tendril-leaved fritillary bulb, tangerine peel, lilyturf root, liquorice and florfenicol. The pharmaceutical composition has the function of superactive antivirus, has strong antivirus and antibiosis actions, remarkable therapeutic effect, fast effect, complete treatment and no relapse, is not easy to generate drug resistance and can be effectively used for preventing and curing the virus diseases of animals. The compound pharmaceutical composition can be powder preparation formulation. The invention also provides feed containing the compound pharmaceutical composition.

A water-soluble florfenicol with high solubility (10000 PPM) and low cost is prepared from florfenicol powder and glucose powder through proportional mixing and stirring.

The present invention discloses certain novel prodrugs of florfenicol and/or of florfenicol analogs, including prodrugs of salts pharmaceutically acceptable salts of florfenicol and its analogs, including nitrogen-containing esters of the secondary alcohol group of florfenicol and of its analogs, and pharmaceutically acceptable salts thereof, compositions containing them, and methods of administering them to subjects. In particular embodiments the prodrugs are sufficiently water-soluble to serve the functions needed of a water-soluble prodrug of florfenicol or of a water-soluble prodrug of a florfenicol analog. A certain subclass of the compounds also possesses the hydrolytic stability needed to maintain the prodrug in solution in the subject's system until appropriate conditions exist when the prodrug can hydrolyze, releasing florfenicol or the florfenicol analog in question.

The invention discloses compound florfenicol injection for an animal. Every 1,000ml of the compound florfenicol injection contains 50 to 300g of florfenicol, 50 to 300g of doxycycline hydrochloride, 150 to 800g of organic solvent, 5 to 90g of complexing agent and 0.2 to 1g of antioxidant. The compound florfenicol injection has the advantages that: (1) the preparation is high in complexation degree and stable in quality, and the doxycycline hydrochloride injection is instable in property; (2) the injection is low in dosage and convenient to use, and the injection twice can be finished at one time; (3) the injection greatly saves the labor cost for veterinary medicine under an intensive feeding condition; and (4) the production of the preparation is controllable in terms of technical conditions, the injection is suitable for industrial production, various raw and auxiliary materials are needed to be accurately weighed in the production process, only the reaction temperature and the reaction time are needed to be controlled without any special technical requirement, and the production technology is easy to master and control.

A compound florfenicol injection for treating the pneumonia and bacterial lung infection of pig is prepared from florfenicol, doxycycline, dimethyl formamide, magnesium dichloride, polyvinyl pyrrolidone, trimethoprim and propanediol. Its preparing process is also disclosed.

The invention discloses a chloramphenicol universal monoclonal antibody hybridoma cell strain and application thereof, belonging to the technical field of food safety immunological detection. The preparation method comprises the following steps: by taking a thiamphenicol analogue 1-(4-aminophenyl)-2-dichlorethamin-1,3-propylene glycol as a hapten, allowing the hapten to pass through diazotization coupling bovine serum albumin (BSA), thereby obtaining a complete antigen; uniformly mixing with a Freund's adjuvant, and performing subcutaneous injection immunotherapy on BALB/c mice; synthesizing an envelope antigen to be used for screening mice serum and cell supernatant by using diazotization; and fusing splenocyte of immune mice with mouse myeloma cells through a PEG method, performing indirect ELISA and indirect competitive ELISA screening and subcloning for three times, thereby obtaining a hybridoma cell strain with mass selection property. The cell strain provided by the invention has high inhibition properties on thiamphenicol, chloramphenicol and florfenicol, and the requirements on chloramphenicol stumpy immunodetection products in the current market can be met.

The invention discloses a method for detecting thiamphenicol, florfenicol and residues of metabolite florfenicol amine in an egg simultaneously. The method comprises the following steps: extracting, purifying and concentrating egg samples; and detecting the obtained product through a fluorescent detector at a position with 225 nm excitation waves and 285 nm transmission waves by taking solution of acetonitrile-monosodium orthophosphate as a mobile phase and by using 5 micrometer C18 column of 250 mm X 4.6 mm and at a flow speed of between 1.0 and 1.2 mL/min, wherein the solution of acetonitrile-monosodium orthophosphate has a concentration of 0.01 mol/L and contains 0.005 mol/lauryl sodium sulfate and 0,1 percent triethylamine; and the volume ratio of the acetonitrile to the solution of NaH2PO4 is 30-37: 70-65. The method for detecting the thiamphenicol, the florfenicol and the residues of metabolite florfenicol amine in the egg simultaneously has the advantages of low cost and high sensitivity.

The invention discloses compound florfenicol injection and a preparation method and application thereof. The compound florfenicol injection comprises main medicaments, injection solvent and local anodyne; and the main medicaments are florfenicol and flunixin meglumine. The compound florfenicol injection is safe and convenient to use, controllable in quality, stable in preparation process, suitable for industrialized production and low in cost; and the compound florfenicol enhances the prevention and treatment effects of porcine or bovine respiratory diseases, improves the survival rate of pigs or cattle, and is suitable for popularization and application.

The invention relates to a preparation method of florfenicol intermediate, in particular to a preparation method of D-threo-2-(dichloromethyl)-4, 5-dihydro-5-(p-(methylsulfonyl) phenyl)-4-oxazole methanol, which comprises the detailed steps as follows: 100 portions of D-p-methylsulfino phenyl ethyl serinate (I) are dissolved in 500 to 700 portions of methanol; then 24 to 27 portions of potassium borohydride are added; the reaction temperature is between 30 and 50 DEG C and the reaction time is between 4 and 8 hours; 80 to 150 portions of methanol are recycled and 230 to 300 portions of glycerol are added; then acid is used for neutralizing the reaction solution to adjust the pH of the solution to be between 7 and 10; and 42 to 45 portions of dochloroacetonitril are added to generate the D-threo-2-(dichloromethyl)-4, 5-dihydro-5-(p-(methylsulfonyl) phenyl)-4-oxazole methanol (II). The preparation method has the characteristics of few technique steps, simple operation and low cost.

The invention belongs to the field of pharmaceutical formulations specially used for animals, and relates to an in-situ gel formulation for florfenicol injection and a preparation method thereof. The in-situ gel formulation is prepared from antibacterial drugs, an in-situ gel substratum and other indispensable auxiliary materials, wherein the antibacterial drugs are specially used for animals; the in-situ gel substratum is accredited in the field. The preparation method is illustrated.The in-situ gel formulation disclosed by the invention is freely flowing liquid at room temperature, forms the semisolid gel after intramuscular injection or hypodermic injection administration, realizes only one-time administration within one treatment course, has the advantages of easiness for preparation, stability in property, convenience for administration, long administration effect lasting time, definite treatment effect, high animal adaptability, no toxic or side effect or adverse reaction, and the like, achieves the broad-spectrum antibacterial effect and is suitable for preventing and treating various sensitive bacteria infection of the animals, such as pigs, sheep, dogs, cats, cattle, and the like.