21 results about "Cinoxacine" patented technology

The invention relates to the technical field of drug analysis and detection, and provides a detection method of moxifloxacin hydrochloride related substances. The related substances of moxifloxacin hydrochloride are detected by adopting a high performance liquid chromatography method, and the detection conditions are as follows: octadecylsilane chemically bonded silica is taken as a filling agent of a chromatographic column; the wavelength of a UV detector is 296 nm; the column temperature is 35-45 DEG C; the flow velocity of the mobile phase is 1.6-1.8 ml / min; the sample injection volume is 10-50 [mu] l; the mobile phase A is phosphate buffer solution-acetonitrile-methanol; the mobile phase B is phosphate buffer solution-acetonitrile-methanol; the elution mode is gradient elution; the diluent is a mobile phase A; according to the method provided by the invention, effective separation between moxifloxacin hydrochloride and various impurities can be realized, the sensitivity is high, the accuracy is good, the reproducibility is relatively good, a good linear relation is shown in a certain range, and qualitative and quantitative determination can be carried out on various impurities in moxifloxacin hydrochloride bulk drugs.

The invention relates to the technical field of drug analysis and detection, in particular to a method for detecting related substances in moxifloxacin hydrochloride bulk drugs. According to the detection method provided by the invention, the separation efficiency of the known impurity (impurity F) can be improved, and the separation degree between the main component and the adjacent impurity can reach 1.5 or above; in addition, a solvent formula is optimized, so that a test sample is more stable, and the detection method is more accurate; the detection accuracy is improved, and the recovery rate is controlled within the range of 93-102%.

The invention discloses a high performance liquid chromatography (HPLC) detection method for enantiomers in moxifloxacin hydrochloride with high separation degree, and belongs to the technical field of medicine detection. The method aims at solving the problems that in the prior art, the leading edge of a main component peak is serious, and the detection accuracy and good peak pattern under the conditions of high separation degree and low content are difficult to meet at the same time, and the adoption of an expensive chiral chromatographic column is avoided. According to the detection method, chiral resolution is realized on a conventional high performance liquid chromatograph by adopting a reversed-phase chromatographic column (such as terminated octadecylsilane chemically bonded silica as a filler). According to the core technical scheme, the unique mobile phase composition is as follows: a water phase contains 0.54 g / L of zinc acetate and 1.17 g / L of L-valine, 1ml of diethylamine is creatively added, and the pH value is adjusted to 5.6 by using dilute sulfuric acid; and an organic phase adopts a methanol-ethanol mixed solution (15: 8) with a specific ratio. And finally, mixing the water phase and the organic phase according to the volume ratio of 77: 23. Under optimal chromatographic conditions (the column temperature is 40 DEG C and the detection wavelength is 295 nm), the method can realize efficient separation between moxifloxacin hydrochloride and enantiomers, the separation degree is greater than 4.5, and the detection accuracy of trace isomers can be realized. A methodological verification result shows that the method is high in sensitivity (the detection limit is 0.0096%, and the quantitation limit is 0.024%), and has a good linear relationship (a correlation coefficient rgt; and the accuracy is good (the recovery rate is between 80.0% and 120.0%). The method can be used for qualitative and quantitative analysis of the moxifloxacin hydrochloride bulk drug and enantiomers in the moxifloxacin hydrochloride preparation.

The invention relates to a 4-oxopyrrolidine derivative as well as a preparation method and application thereof. The structural formula of the 4-oxopyrrolidine derivative is # imgabs0 #, wherein R1 and R2 are independently selected from straight-chain or branched-chain C1-C18 alkyl groups; y is selected from a fluorine atom, a chlorine atom, a bromine atom, a methylsulfonyl group, a p-toluenesulfonyl group, a nitrobenzene methylsulfonyl group and a trifluoromethylsulfonyl group. The preparation method comprises the following steps that a compound shown in a formula (II) and a compound shown in a formula (III) react in an aprotic solvent for 20-28 h under the alkaline condition, after aftertreatment, a compound shown in a formula (I) is obtained, and the reaction route is as follows: # imgabs1 #. Compared with the prior art, the preparation method is high in yield, low in by-product proportion, low in solvent cost and suitable for industrial production. The method can be used for preparing the moxifloxacin intermediate.

1. Name of the product in this design: Packaging Box (Moxifloxacin Hydrochloride Tablets). 2. Intended use of this design: packaging pharmaceuticals. 3. The key design elements of this product are the combination of shape, pattern, and color. 4. The image or photograph that best illustrates the key design points: unfolded diagram. 5. The design for which protection is sought includes color.

The invention relates to the technical field of medicine crystallization, and discloses a preparation method of moxifloxacin hydrochloride crystal form II large-particle crystals, which comprises the following steps: S1, dissolving moxifloxacin tartrate in an ethanol water solution; s2, sequentially adding concentrated hydrochloric acid and moxifloxacin hydrochloride crystal form II rod-like seed crystals, and stirring to grow the crystals; s3, concentrated hydrochloric acid is continuously added in batches, and stirring and crystal growing are performed once after each batch of concentrated hydrochloric acid is added; the temperature is maintained at 30-60 DEG C during the S2 and S3; and S4, cooling, carrying out crystal growth, and separating out a product, thereby obtaining the moxifloxacin hydrochloride crystal form II large-particle crystal. By adopting the preparation method disclosed by the invention, the obtained moxifloxacin hydrochloride crystal form II crystal has a thick rod-shaped morphology and is relatively large and uniform in size.

The invention discloses a method for detecting N-nitroso moxifloxacin in moxifloxacin hydrochloride sodium chloride injection, the detection method adopts a high performance liquid chromatography-mass spectrometry method for detection, and the method comprises the following steps: providing a moxifloxacin hydrochloride solution to be detected, the moxifloxacin hydrochloride solution to be detected comprises a test solution and a reference solution; and analyzing the moxifloxacin hydrochloride solution to be detected by adopting a high performance liquid chromatography-mass spectrometry method, and recording a chromatogram of the moxifloxacin hydrochloride solution to be detected. The detection method can effectively detect the content of N-nitroso moxifloxacin in the moxifloxacin hydrochloride sodium chloride injection, is simple to operate, good in specificity and high in sensitivity and accuracy, and can effectively control the product quality.

The application relates to the technical field of pharmaceutical analysis, and particularly discloses a method for detecting genotoxic impurities in moxifloxacin hydrochloride raw materials or preparations. The method is detected by high performance liquid chromatography-mass spectrometry, liquid chromatography conditions are as follows: a C18 chromatographic column is used, a 0.05%-0.2% formic acid aqueous solution is used as a mobile phase A, a 0%-0.2% formic acid acetonitrile solution is used as a mobile phase B, and gradient elution is carried out; the mass spectrometry adopts an ESI ion source, a positive ion detection mode, a parent ion is 431.15 m / z, a daughter ion is 401.18 m / z, and a collision voltage is 10V-25V. The method provided by the application has strong specificity and high sensitivity, the detection limit is 0.625ppm, the blank that the prior art cannot effectively detect N-nitrosomoxifloxacin impurities in moxifloxacin hydrochloride raw materials or preparations is made up, and then the safety risk of moxifloxacin hydrochloride drugs is reduced.

The invention belongs to the technical field of preparation of medical intermediates, and particularly relates to a preparation method of a monomethyl impurity of an intermediate (S, S)-2, 8-diazabicyclo [4.3. 0] nonane of a quinolone antibacterial drug moxifloxacin hydrochloride, which comprises the following steps: by taking (S, R) 8-benzyl-7, 9-dioxo-2, 8-diazabicyclo [4.3. 0] nonane as an initial raw material, reacting at the temperature of 60-80 DEG C to obtain a monomethyl impurity of the intermediate (S, S)-2, 8-diazabicyclo [4.3. 0] nonane; a crude compound is obtained through condensation, reduction and debenzylation, and the crude compound is rectified, separated and purified to obtain the high-purity moxifloxacin side chain monomethyl impurity. The method has the characteristics that the synthesis route is short, the operation is simple, and the obtained moxifloxacin side chain monomethyl impurity product is high in purity and can be applied to research of impurity reference substances.

The invention discloses a moxifloxacin nano drug delivery system as well as a preparation method and application thereof, and the moxifloxacin-loaded infected microenvironment lipase response nano drug delivery system is constructed on the basis of a comprehensive strategy of drug-assistant synergistic sensitization and antibiosis, improvement of permeability of a bacterial outer membrane, inhibition of activity of a bacterial efflux pump and removal of a biofilm. The sensitivity of moxifloxacin to multi-drug-resistant pseudomonas aeruginosa is enhanced, the pathogenicity of bacteria is reduced, and the risks of infection recurrence and drug resistance are reduced while the infection clearance rate is increased. And the antibiotic adjuvant adopts natural biodegradable epsilon-polylysine, so that the side effect of lung inhalation is reduced, and the biological safety of the nano-drug delivery system is improved.

The invention discloses gel eye drops containing bromfenac sodium and moxifloxacin hydrochloride as well as a preparation method and application of the gel eye drops, and belongs to the technical field of medicines. Comprising the following raw materials in parts by weight: 0.8-1.2 parts of bromfenac sodium, 0.8-6 parts of moxifloxacin hydrochloride, 15-30 parts of a gel matrix, 3-15 parts of sodium hyaluronate, 8-12 parts of an osmotic pressure regulator, 7.0-9.0 parts of citric acid, 0.02-0.05 part of sodium citrate and 950-1050 parts of purified water. The bromfenac sodium and the moxifloxacin hydrochloride are compounded, and the gel matrix, the sodium hyaluronate, the osmotic pressure regulator, the citric acid, the sodium citrate and the purified water are matched, so that the compound gel eye drops which are free of preservatives, low in irritation, good in stability, capable of improving the bioavailability of drugs and capable of achieving anti-inflammatory and antibacterial synergistic interaction are achieved, and eye inflammation can be effectively treated.

The invention discloses a preparation method of a moxifloxacin hydrochloride intermediate with high yield, high purity and low cost, and aims to overcome the technical defects of low resolution yield, need of additional acid addition, single solvent system, complex resolution agent recovery process and limited salifying efficiency in the prior art. According to the method, cis-8-benzyl-7, 9-dioxo-2, 8-diazabicyclo [4.3. 0] nonane (a compound as shown in a formula I) is taken as a raw material, N-acetylphenylalanine (including L-type and D-type) is taken as a resolving agent, acid does not need to be additionally added in a water-alcohol-ester ternary solvent system, efficient resolution of the enantiomer is directly realized through a salt forming reaction, and the yield of the enantiomer is increased. And the high-purity diazabicyclo compounds shown in the formulas IIIa and IIIb can be obtained without a refining step. The resolution yield can reach 90% or above, the recovery process of the resolving agent is simple and efficient, the recovery rate is larger than or equal to 95%, the resolving agent can be stably and circularly applied for five times or above, the resolution yield is still larger than or equal to 90% after the resolving agent is applied, the comprehensive production cost is reduced by 40%-60% compared with the prior art, and the method has outstanding industrial application advantages.

The application discloses a colorimetric copper ion fluorescent probe and synthesis and application thereof, which has a fluorophore and a copper ion recognition group, wherein the copper ion recognition group is one of commercial drugs of norfloxacin, levofloxacin, moxifloxacin and gatifloxacin. The copper ion fluorescent probe can be used for qualitative and colorimetric detection of copper ions, and is especially used in the fields of solution / cell / tissue / living body imaging, biological labeling or sensing.

The invention provides a preparation method of a moxifloxacin side chain key intermediate, and belongs to the technical field of medical intermediate production, and the preparation method comprises the following steps: firstly salifying a compound 1 and L-(+) tartaric acid in proportion, dissociating the precipitated solid to obtain a compound 3, concentrating the filtrate, and simply refining to obtain a compound 2 with ee value of 100%, and the single resolution yield is 39%. In addition, the compound 3 is subjected to racemization to obtain a compound 1, and then the compound 1 is split again; and the yield can reach 85% or above after repeated cyclic resolution. L-(+) tartaric acid is used for resolution, a product with a high ee value is obtained in combination with a simple refining process, the resolution yield is improved to a certain extent, and the production cost is reduced.

This invention relates to a method for preparing 6-benzyl-1,2,3,4-tetrahydro-6H-pyrrolo[3,4-B]pyridine-5,7-dione and its application. The method for preparing 6-benzyl-1,2,3,4-tetrahydro-6H-pyrrolo[3,4-B]pyridine-5,7-dione involves reacting (1R,6S)-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4,3,0]nonane in an organic solvent under blue light irradiation with the aid of a photosensitizer and an oxidizing agent to obtain 6-benzyl-1,2,3,4-tetrahydro-6H-pyrrolo[3,4-B]pyridine-5,7-dione. This preparation method not only has mild reaction conditions, short reaction time, simple operation, and environmental friendliness, but also has high product conversion rate and good selectivity. It can be used for large-scale industrial production and can be better applied to the synthesis of moxifloxacin, thereby improving the utilization rate of raw materials in the synthesis of moxifloxacin.

The invention discloses a green synthesis method of moxifloxacin hydrochloride, which comprises the following steps: under a heating condition, reacting moxifloxacin cyclization ester with moxifloxacin ((S, S)-2, 8-diazabicyclo [4, 3, 0] nonane) in a solvent, alkali and catalyst system to obtain moxifloxacin ester, and then carrying out hydrolysis one-pot method in an acidic system to obtain the moxifloxacin hydrochloride. The moxifloxacin hydrochloride is directly prepared. The invention provides a green synthesis method of moxifloxacin hydrochloride. According to the green synthesis method, moxifloxacin is obtained through direct reaction of moxixane cyclization ester and moxixane. According to the method, the moxifloxacin serving as a target product is synthesized by taking the moxixane cyclization ester as a raw material without forming a chelate compound with boric acid ester and directly reacting with the moxixane through a one-pot method, no three wastes are generated in the preparation process, and the method has the advantages of short reaction steps, mild conditions, high yield and the like.

The present application relates to the field of ophthalmic drugs, and particularly relates to an ophthalmic composition, a preparation method and application thereof, the ophthalmic composition comprising a compound as shown in formula I, an osmotic pressure regulator, a pH regulator and water for injection; the pH value of the ophthalmic composition is 4.0-6.0; the concentration of the compound as shown in formula I is 0.1-3.0% w / v, and the concentration of the osmotic pressure regulator is 0.3-10.0% w / v; the antibacterial activity against Streptococcus pneumoniae, Staphylococcus aureus and Staphylococcus epidermidis is 2-8 times that of levofloxacin and moxifloxacin hydrochloride; the antibacterial activity against Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli and Pseudomonas aeruginosa is also strong, and is equivalent to that of levofloxacin and moxifloxacin hydrochloride; the irritation is small, the light stability and high-temperature stability are good, the quality and drug safety are guaranteed, and the application value is good.

The invention provides a method for detecting the content of 6-nitroso octahydro-1H-pyrrolo [4, 3-b] pyridine (impurity 97) and 1-nitroso octahydro-1H-pyrrolo [4, 3-b] pyridine (impurity 100) in moxifloxacin hydrochloride, the method adopts an ultra-high performance liquid chromatography-tandem mass spectrometry method, the adopted mobile phase is an ammonium acetate-methanol solution, and the column temperature is 20-30 DEG C. The detection method has high sensitivity, the quantitation limits of the impurity 97 and the impurity 100 in the moxifloxacin bulk drug are respectively 0.33 ppm and 0.34 ppm, the quantitation limits of the impurity 97 and the impurity 100 in the moxifloxacin tablet are respectively 0.36 ppm and 0.37 ppm, and according to related guidance principles and methodology verification, the related requirements are met, and the detection method has good clinical application prospects. The method provided by the invention can be used for detecting the contents of the two impurities in a moxifloxacin hydrochloride raw material medicine and a moxifloxacin hydrochloride tablet.

The invention relates to the technical field of pharmaceutical analysis, and particularly discloses a method for detecting genotoxic impurities in a moxifloxacin hydrochloride raw material or a preparation thereof. According to the method, a high performance liquid chromatography and mass spectrometry combined method is adopted for detection, and liquid chromatography conditions are as follows: a C18 chromatographic column is used, a formic acid aqueous solution with the volume concentration of 0.05%-0.2% is used as a mobile phase A, an acetonitrile solution of formic acid with the volume concentration of 0%-0.2% is used as a mobile phase B, and gradient elution is performed; the mass spectrum adopts an ESI ion source and positive ion detection mode, the parent ion is 431.15 m / z, the daughter ion is 401.18 m / z, and the collision voltage is 10V-25V. The method provided by the invention is strong in specificity and high in sensitivity, the detection limit is 0.625 ppm, the blank that N-nitroso moxifloxacin impurities in a moxifloxacin hydrochloride raw material or a preparation cannot be effectively detected in the prior art is filled up, and the medication safety risk of a moxifloxacin hydrochloride medicine is further reduced.

The application provides a boron removal method of moxifloxacin hydrochloride and a preparation method of pure moxifloxacin hydrochloride, and belongs to the technical field of medicine preparation. In the application, LSC-800 resin is used for adsorbing and removing boric acid under the condition that the pH value is 8-9. The LSC-800 resin is a macroporous structure chelating resin which is crosslinked by styrene and divinylbenzene and has N-methylglucosamine groups. The polyol group part of the LSC-800 resin can generate complex anions with boric acid groups, and the amine group part of the LSC-800 resin can capture the generated complex anions as anion exchange groups, so that the boric acid ions in the boric acid-containing moxifloxacin hydrochloride can be selectively adsorbed, and the boric acid ions can be effectively removed. The results of the examples show that no boric acid is detected in the obtained moxifloxacin hydrochloride by using the boron removal method.

The invention discloses a method for detecting a moxifloxacin hydrochloride residual solvent. The method comprises the following steps: (1) respectively preparing a blank solution, a reference solution and a test solution; (2) sample injection detection; chromatographic conditions are as follows: an instrument used is a gas chromatograph with a hydrogen flame ionization detector, a chromatographic column is a capillary column taking polyethylene glycol as a stationary liquid, headspace sample injection is adopted to inject into the gas chromatograph, hydrogen is taken as a carrier gas, sample injection detection is performed respectively to obtain a chromatogram of a reference substance solution and a chromatogram of a test sample solution, and the chromatogram of the reference substance solution and the chromatogram of the test sample solution are calculated. And detecting and analyzing by adopting an external standard method to complete the determination of the moxifloxacin hydrochloride residual solvent. According to the method, a plurality of residual solvents are placed in the same system for detection, the organic solvents are completely separated, the linear relation is good in the investigated range, and the detection efficiency is greatly improved.