51 results about "Marbofloxacin" patented technology

The invention discloses a hybridoma cell strain capable of secreting monoclonal antibodies to quinolones and application of the monoclonal antibodies thereof. Ciprofloxacin (CIP) coupled with bovine serum albumin is used as an antigen to immunize BALB / c mice and cell fusion, screening and cloning are carried out so as to obtain one hybridoma cell strain 1F1 capable of stable passage and secretion of monoclonal antibodies (MAb) to quinolones, wherein, the accession number of the hybridoma cell strain 1F1 is CGMCC No. 5608. The titres of ascitic fluids of the 1F1 monoclonal antibodies are up to 10<-7>, and the type and the subclass of the monoclonal antibodies are IgG1 and kappa chain. According to indirect competitive ELISA analysis, the 1F1 monoclonal antibodies perform specific reactions to quinolones like ciprofloxacin, enrofloxacin, ofloxacin, danofloxacin, norfloxacin, enoxacin, marbofloxacin, sarafloxacin and difloxacin. An ELISA method, a kit and test paper for detecting residual of quinolones in food are developed by using the 1F1 monoclonal antibodies.

The invention mainly discloses a novel method for preparing marbofloxacin, which comprises the following steps: under the protection of inert gases, 2,3,4,5-phenyl tetrafluoride formoxyl alkyl ester forms negative ions with alkali in an inert organic solvent, is condensed with imidic salt to obtain N-dimethyl substitutive enamine derivative, and reacts with N - methyl hydrazide in organic acid to obtain N-methyl-N-acyl substitutive enamine derivative; under the reflux state, the N-methyl-N-acyl substitutive enamine derivative is catalyzed by alkali to obtain quinoline carboxylic ether; the quinoline carboxylic ether takes water as a solvent, is catalyzed with alkali at proper temperature and is neutralized to obtain quinoline carboxylic acid; under the action of an acid-binding agent, the quinoline carboxylic acid is condensed with N-methyl piperazine to obtain a condensed piperazine substance; the condensed piperazine substance is heated to proper temperature in an alkalis hydroxid water solution, is kept at the temperature and is neutralized to obtain hydrolysate; and the hydrolysate takes water as a solvent and is reacted with dialkoxy methane or methylene halide to obtain the marbofloxacin under the catalysis of the catalyzer. The invention has high yield, thereby facilitating industrialized production at large scale.

The invention discloses a preparation method of Marbofloxacin, which comprises the following steps: (1) mixing a compound disclosed as Formula (V) with phenylmethane, triethylamine and N-methylpiperazine, heating to react for 8-12 hours, cooling to room temperature, adding purified water and potassium hydroxide, reacting at 60-90 DEG C for 3-5 hours, cooling to 20-25 DEG C, separating out a waterphase, regulating the pH value of the water phase to 6.8-7.2 with hydrochloric acid, extracting with dichloromethane, and concentrating while depressurizing to obtain a compound disclosed as Formula (IV); and (2) reacting the compound disclosed as Formula (IV) with potassium hydroxide in medium water at 125-160 DEG C under the pressure of 0.1-0.4 Mpa for 5-12 hours to obtain a compound disclosed as Formula (II), dropwisely adding a formic acid water solution and a formaldehyde water solution when the temperature drops to 40-50 DEG C, carrying out cyclization reaction at 70-75 DEG C for 6-10 hours, and carrying out after-treatment on the reaction product to obtain the Marbofloxacin. The invention utilizes a new intermediate to prepare Marbofloxacin, has the advantages of short reaction time, low cost and high product purity, and is suitable for commercial production.

The invention discloses marbofloxacin freeze-dried powder for injection and a preparation method and application thereof. The marbofloxacin freeze-dried powder consists of the following components: 250g of marbofloxacin, an appropriate amount of lactic acid, 4.8g of injectable activated carbon and the balance of water for injection, wherein the solution is 5000ml in total. The preparation process disclosed by the invention comprises the following steps of: (1) preparing the water for injection; (2) sterilizing rubber plugs; (3) purifying penicillin bottles; and (4) preparing the marbofloxacin freeze-dried powder. The marbofloxacin freeze-dried powder has the advantages of no influence by quality of water in application regions, accuracy in dosage, convenience for use and the like; and the defect that marbofloxacin is water-insoluble is overcome.

The invention discloses a marbofloxacin soluble pulvis. The marbofloxacin soluble pulvis comprises, by weight, 4.0-25% of marbofloxacin, 1.0-45% of sodium carbonate, 0.1-1.0% of a perfume, and the balance of a soluble filler. The marbofloxacin soluble pulvis prepared through a method disclosed in the invention has the characteristics of simplicity in use, low cost, complete fragrance, stability in storage, convenience in transportation, and good water solubility. An aqua prepared in the invention greatly improves the curative effects of themarbofloxacin soluble pulvis, is a novel wide-spectrum and high-efficiency special pulvis for animals, and enriches the variety of antibiotics in the veterinary medicine market.

The invention belongs to the technical field of molecularly imprinted polymers, and particularly discloses a magnetic carboxylation nano-crystalline cellulose amino-functionalization surface molecularly imprinted polymer. Magnetic carboxylation nano-crystalline cellulose Fe3O4@CCNs serves as a carrier, ofloxacin OFX serves as template molecules, glycidyl methacrylate GMA serves as a functional monomer, and through a polymerization reaction, the magnetic carboxylation nano-crystalline cellulose amino-functionalization surface molecularly imprinted polymer Fe3O4@CCNs@MIPs is formed. Fluoroquinolone drugs in a water body can be selectively extracted, and include ofloxacin OFX, lomefloxacin LOM, gatifloxacin GAT, sarafloxacin SARA, marbofloxacin MARBO, orbifloxacin OBX, difloxacin DFX, ciprofloxacin CIP, enrofloxacin ENRO, sparfloxacin SPX, and moxifloxacin MFX, the recovery rate reaches 81.2%-93.7%, and the adsorption capacity reaches 33 mg / g after adsorption / elution are repeated seven times.

The invention discloses a method and special immune affinity adsorbent for extracting quinolone compound and / or sulfonamide compound. The immune affinity adsorbent consists of a solid-phase carrier and Norfloxacin monoclonal antibody and / or sulfamethoxazole monoclonal antibody coupled with the carrier, wherein the Norfloxacin monoclonal antibody and the sulfamethoxazole monoclonal antibody are obtained by taking Norfloxacin hapten, sulfamethoxazole hapten and carrier protein conjugate as immunogen; the quinolone compound is at least one of the following 13 types of compounds: Ciprofloxacin, Norfloxacin, Pefloxacin, Ofloxacin, Enoxacin, Marbofloxacin, Lomefloxacin, Danofloxacin, Enrofloxacin, Sarafloxacin, Difloxacin, Oxolinic acid and Flumequine; and the sulfonamide compound is at least one of the following 6 types of compounds: sulfapyridine, sulfathiazole, sulphapyridine, sulfamethizole, sulfamonomethoxine and sulfamethoxazole.

The invention discloses an oil injection containing antibacterial agents / solid polyethylene glycol drug-loading particles. The oil injection is prepared by consisting of the drug-loading particles through antibacterial agents and solid polyethylene glycol and suspending the drug-loading particles in an oil medium. The antibacterial agents comprise enrofloxacin, danofloxacin mesylate, Marbofloxacin, mequindox, tilmicosin, tylosin, oxytetracycline hydrochloride, ceftiofur hydrochloride, cefquinome sulfate, lincomycin hydrochloride, florfenicol, erythrocin and doxycycline hydrochloride; preferentially the polyethylene glycol with the molecular weight of more than 6000 is used for preparing the preparation; more preferentially, any one of isopropyl myristate, soybean oil for injection, corn oil and tea-seed oil is used for preparing the preparation. Hydroxypropyl methyl cellulose or high-substituted hydroxy propyl cellulose can be added into the preparation.

The invention discloses a marbofloxacin-calcium chelate and a synthetic method and application thereof. The synthetic method of the marbofloxacin-calcium chelate comprises the following steps: 1, weighing marbofloxacin and calcium nitrate according to a stoichiometric ratio, then weighing triethylamine with the equal substance amount with the marbofloxacin, and dissolving in a polar solvent; 2, performing a reaction on the obtained solution under the condition of 20 to 70 DEG C; 3, when a product exists in the reaction solution mainly in a precipitate mode, filtering the obtained reaction solution and washing and drying precipitates to obtain the target product, and when the product is mainly dissolved in the reaction solution, concentrating the obtained reaction solution to remove most of solvent, adding excessive ethanol, separating out the precipitates and washing and drying the precipitates to obtain the target product. By inspecting the in-vitro antibacteral activity and the in-vivo acute toxicity of the chelate by the applicant, a result shows that the in-vitro bacteriostasis effect of the marbofloxacin-calcium chelate is equivalent to that of the marbofloxacin, but the in-vivo acute toxicity of the marbofloxacin-calcium chelate is obviously lower than that of the marbofloxacin. The structural formula of the marbofloxacin-calcium chelate is as shown in the following formula (referring to the specification).

The invention provides a Marbofloxacin suspension. Marbofloxacin is taken as main medicine in the suspension, and the Marbofloxacin suspension at least comprises the following components in parts by weight: 100 parts of Marbofloxacin, 30 to 40 parts of a suspending agent, 0.5 to 2 parts of a preservative, 10 to 20 parts of a wetting agent, 0.5 to 2 parts of a flavoring agent, 2 to 8 parts of a sweetening agent and 3000 to 4000 parts of purified water. The invention also provides a preparation method of the Marbofloxacin suspension. According to the Marbofloxacin suspension, which is high in stability, high in quality, obvious in curative effect and little in adverse reaction, prepared by taking Marbofloxacin as main medicine and the preparation method thereof provided by the invention, theMarbofloxacin suspension prepared by using the method, namely insoluble solid medicine, is dispersed in a liquid medium.

An anti-quinolone antibiotic class specific monoclonal antibody hybridoma cell strain YH6 and an application thereof belong to the technical field of immunochemistry. The monoclonal cell strain YH6 is preserved in China General Microbiological Culture Collection Center with the preservation number of CGMCC No.12024. A monoclonal antibody secreted by the YH6 is detected by indirect competitive enzyme-linked immunosorbent assay, and has cross reaction with the following 21 pyrethroids: norfloxacin, ofloxacin, enrofloxacin, ciprofloxacin, flumequine, nafloxacin, enoxacin, lomefloxacin, levofloxacin, pefloxacin, nalidixic acid, danofloxacin, pyridine acid, cinoxacin, oxolinic acid, marbofloxacin, pazufloxacin, sparfloxacin, gatifloxacin, orbifloxacin and fleroxacin, and the IC50 value of the monoclonal antibody is 0.1-50 ng / mL. The class specific monoclonal antibody can be used for developing colloidal gold immunochromatographic test strips and immunosensors, provides a raw material for the immunodetection of quinolone antibiotic residues in foods, and has practical application values.

The invention discloses a refining method of marbofloxacin. The refining method comprises the following steps of (1) dissolving a marbofloxacin crude product in a certain amount of water, stirring until no obvious particles exist, then adding a certain amount of acid, stirring for 20min to 30min, and carrying out suction filtration; (2) dissolving a filter cake in a certain amount of solvent or mixed solvent, adding alkali to adjust PH to 7.0 to 9.0, stirring for clarifying, adding activated carbon, warming at the temperature of 40 DEG C to 60 DEG C, reflowing for 20min to 40min, filtering, and collecting a filter liquor; (3) concentrating the filter liquor, after concentrating to a certain temperature, starting to cool to 20 DEG C to 30 DEG C, continuously cooling to 0 DEG C to 10 DEG C, keeping warm for 30min to 50min, carrying out suction filtration, washing and drying.

The invention discloses a new application of quinolone compounds as bactericides in prevention and treatment of bacterial diseases and citrus canker of crops. The quinolone compounds comprise floroxacin, enofloxacin, gatifloxacin, moxifloxacin hydrochloride, enrofloxacin, marbofloxacin, floxacin, mononorfloxacin mesylate, prulifloxacin, Balofloxacin, pazufloxacin mesylate, pipemidic acid, sparfloxacin, difloxacin hydrochloride, lomefloxacin hydrochloride, pefloxacin, tosufloxacin mesylate, Cinoxacin, galafloxacin, besifloxacin hydrochloride, ofloxacin, nalidixic acid, Clinafloxacin and Sitafloxacin. The quinolone compounds can be used for preventing and treating bacterial diseases caused by citrus canker pathogens, especially gatifloxacin, moxifloxacin hydrochloride, mononorfloxacin mesylate, sparfloxacin, tosufloxacin mesylate, clinafloxacin and sitafloxacin, has excellent bacteriostatic activity on citrus canker pathogens, and can be used for preventing and treating bacterial diseases of crops.

The invention discloses marbofloxacin beef flavored tablets and a preparation method thereof; each 1000 slices of the flavored tablets are prepared from 20 g of marbofloxacin, 425-465 g of D-(+)-lactose monohydrate, 75 g of cross-linked povidone, 5 g of povidone K-30, 45-85 g of a beef extract, 4.8 g of silica, 6 g of magnesium stearate and 100 g of purified water as raw materials. The preparation method comprises the following steps: 1) preparing a mixed solution containing povidone K-30 and the beef extract; 2) preparing a soft material; 3) preparing wet particles; 4) drying; 5) screening and stabilizing the size; 6) adding silica and magnesium stearate into the size-stabilized particles in the step 5), and mixing evenly; and 7) pressing the particles mixed in the step 6) into drug tablets by using a tabletting machine. The flavored tablets are good in palatability and convenient to administrate, has quality meeting requirements of the Pharmacopoeia, and has treatment effects and side effects the same as those of other marbofloxacin tablets without addition of flavoring agents in markets. The preparation method is simple, the operation is convenient, and the preparation cost is low.

The invention provides marbofloxacin flavored tablets and a preparation method therefor. The marbofloxacin flavored tablets comprise the following ingredients in parts by weight: 4-18 parts of marbofloxacin, 50-83.1 parts of filler, 5-30 parts of disintegrant, 0.1-2 parts of lubricant and 0.05-5 parts of flavoring agent. The invention further relates to the preparation method for the marbofloxacinflavored tablets. According to the method provided by the invention, the marbofloxacin is adopted as an effective pharmaceutical ingredient of the oral-administration flavored tablets, and the existing formula is optimized; and thus, the oral-administration flavored tablets prepared by the method can have the following advantages that the palatability is better, the administration is convenient,and the oral-administration flavored tablets can serve as an oral-administration drug for treating deep and shallow skin infection, respiratory tract infection and urinary tract infection of a pet.

The invention discloses novel application of a fluoroquinolone medicine and application of the fluoroquinolone medicine in preparation of a sensitizer of a pseudomonas aeruginosa (P.aeruginosa) inhibitor. The fluoroquinolone medicine is prepared from gemifloxacin, sparfloxacin, enrofloxacin, ciprofloxacin, sarafloxacin, moxifloxacin, pefloxacin, tosufloxacin, orbifloxacin, prulifloxacin, marbofloxacin, levofloxacin, flumequine or / and pazufloxacin; the pseudomonas aeruginosa is pseudomonas aeruginosa DK2 or PAO1; the pseudomonas aeruginosa inhibitor is polymyxin B or colistin.

The invention belongs to the technical field of antibacterial heterocyclic compounds or pharmaceutical preparations with specific treatment activity and relates to a marbofloxacin synthesizing method. 2,4,5-trifluoro-3-methoxy-benzoyl chloride serves as a starting material for preparing marbofloxacin by grafting, amination, cyclization, piperazine condensation, hydrolysis, re-cyclization, alkali dissolution and acid regulation. The marbofloxacin synthesizing method applied to marbofloxacin preparation has advantages of high yield, mild reaction conditions, low pollution and the like.

The invention relates to a marbofloxacin preparation method, a multi-step reaction is continuously carried out, the efficiency is high, and the preparation method has the advantages that the synthesis route is short, all the reagents are conventional and easy for commercial purchase, and the operation is simple.

The invention relates to preparation for a marbofloxacin key intermediate, and concretely relates to preparation of 6,7-difluoro-8-hydroxy(or fluoro)-1-methylamino-4-oxo-1,4-dihydroquinoline-3-carboxylate, and the key step relates to direct condensation of methylhydrazine and 6,7-difluoro-8-hydroxy(or fluoro)-4-oxo-4-hydro-benzypyran-3-carboxylate.

The invention relates to a marbofloxacin micro-capsule and a preparation method of the marbofloxacin micro-capsule. The preparation method comprises the following steps: (1) preparing a wall material solution, (2) preparing a core material solution, (3) carrying out emulsification and reduced pressure distillation: slowly dropwise adding the core material solution prepared in Step (2) into the wall material solution prepared in Step (1) under a high-speed shearing condition, carrying out the reduced pressure distillation at the same time, recovering a dichloromethane / absolute ethyl alcohol mixed solution, and continuing the reduced pressure distillation after dropwise adding, and (4) carrying out spray drying, wherein the system temperature is 10-40 DEG C; a vacuum degree is 0.01-0.07Mpa; the dropwise adding time is 0.5-2h; and the shearing speed is 5000-10000 r / min. The sensitivity of marbofloxacin to light can be reduced; the drug efficacy is prolonged; an unpleasant odor is covered; the solubility is improved; in addition, various preparations, such as powder, a tablet, a capsule and controlled-release agent can be prepared very conveniently; and animal administration is facilitated.

The invention relates to a composition for treating porcine respiratory tract infection and a preparation method of the composition. The composition is prepared from the following raw materials in percentage by weight: 1-5 % of marbofloxacin, 1-5 % of tiamulin fumarate, 5-15 % of tilmicosin phosphate, 5-15 % of lincomycin hydrochloride, 5-15 % of chlortetracycline hydrochloride, the balance of anhydrous glucose. All the components are grinded, the obtained powder is screened by adopting a No.5 sieve, the screened powder is sufficiently and uniformly mixed, and thus the composition for treating porcine respiratory tract infection is obtained. Compared with the prior art, the composition has the advantages that the plurality of medicines which can be mixed for use are comprehensively selected, the situation that some pathogenic bacteria have drug resistance to some medicines, consequently, treatment failure is caused, is avoided, the drug resistance probability of pathogens is reduced, so that the pathogenic microorganism resisting range is wide, the antibacterial effect is strong, and disease recovery is facilitated.

The medicine relates to a medicine for increasing yields and preventing and treating bacterial diseases used for silkworms and applications thereof. Raw materials of the medicine comprise marbofloxacin, sodium glutamate and water. The medicine is prepared by fully mixing the raw materials. The marbofloxacin and the sodium glutamate are mixed to prepare the medicine for increasing the yields and preventing and treating the bacterial diseases used for silkworms for the first time. The medicine has a yield increasing effect when being used for preventing and treating septicaemia caused by bacillus thuringiensis var sotto ishiwata, bacillus bombysepticus and serratia marcescens and can greatly increase the yield of silkworm cocoons.

Antiinfectious composition comprises a pyrido[3,2,1-ij]benzoxadiazine derivative (I) or its salt and a solubilizer in a carrier. Antiinfectious composition comprises a pyrido[3,2,1-ij]benzoxadiazine derivative of formula (I), or its salt, and a solubilizer in a carrier. X : H, halo or OH; R 1>1-piperazinyl (optionally 4-substituted with Me), acetyl of 4-aminobenzyl; morpholino; 1-pyrrolidinyl (optionally 3-substituted with Cl, NH 2, aminomethyl, methylaminomethyl, ethylaminomethyl or OMe); 1-imidazolyl (optionally 4-substituted with Me); or 1-piperidinyl (optionally 4-substituted with OH or OMe); R 2>1-10C alkyl. [Image] - ACTIVITY : Antibacterial; Virucide; Respiratory-Gen.; Endocrine-Gen.; Uropathic; Gastrointestinal-Gen.; Cardiovascular-Gen.; Dermatological; Muscular-Gen.; Auditory; Ophthalmological. An aqueous solution of marbofloxacin (15 g / 100 ml) and gluconolactone (8.11 g / 100 ml) was administered to pigs by intramulsular injection at a dose of 8 mg / kg. The lesion volume after 1 week was 9 cm 3>, compared with 32 cm 3> using an aqueous solution of marbofloxacin (10 g / 100 ml) and gluconolactone (8 g / 100 ml). - MECHANISM OF ACTION : None given.

The invention provides a method for preparing marbofloxacin nanoparticles. The method comprises the following steps: 1, uniformly mixing chitosan and a glacial acetic acid solution, adding a marbofloxacin raw material drug into the mixture, and performing stirring and dissolving to obtain a marbofloxacin-chitosan solution; 2, adjusting the pH value of the marbofloxacin-chitosan solution to be acidic, dropwise adding a sodium polyphosphate solution into the acidic solution under a stirring state to obtain a marbofloxacin-chitosan nanoparticle colloidal solution; and 3, performing high-speed refrigerated centrifugation on the marbofloxacin-chitosan nanoparticle colloidal solution to obtain the marbofloxacin nanoparticles. The marbofloxacin-chitosan nanoparticles have high encapsulation efficiency, high drug loading capacity and stable property, can overcome the problem that marbofloxacin is sensitive to light, can be used for improving the solubility of marbofloxacin to a certain extentto cover the undesirable odor of the drug, and has an excellent application prospect.

The invention belongs to the technical field of molecularly imprinted polymers, and particularly discloses a magnetic carboxylation nano-crystalline cellulose amino-functionalization surface molecularly imprinted polymer. Magnetic carboxylation nano-crystalline cellulose Fe3O4@CCNs serves as a carrier, ofloxacin OFX serves as template molecules, glycidyl methacrylate GMA serves as a functional monomer, and through a polymerization reaction, the magnetic carboxylation nano-crystalline cellulose amino-functionalization surface molecularly imprinted polymer Fe3O4@CCNs@MIPs is formed. Fluoroquinolone drugs in a water body can be selectively extracted, and include ofloxacin OFX, lomefloxacin LOM, gatifloxacin GAT, sarafloxacin SARA, marbofloxacin MARBO, orbifloxacin OBX, difloxacin DFX, ciprofloxacin CIP, enrofloxacin ENRO, sparfloxacin SPX, and moxifloxacin MFX, the recovery rate reaches 81.2%-93.7%, and the adsorption capacity reaches 33 mg / g after adsorption / elution are repeated seven times.

The present invention relates to a formulation and method for treating an ear infection, especially otomycosis and otitis externa, by administering a one-time only treatment comprising an antibiotic, antifungal, and an anti-inflammatory in a thick, otic carrier. In one embodiment, the formulation comprises a therapeutically effective amount of active ingredients including a marbofloxacin, terbinafine and / or clotrimazole and dexamethasone.