79 results about "Flurbiprofen axetil" patented technology

The invention relates to a preparation method of flurbiprofen axetil. The method comprises the following steps of: preparing 4-bromine-2-fluoroanili from fluoroaniline under the action of 1,3- dibromo-5,5-dimethyl hydantoin; condensing 4-bromine-2-fluoroanili with benzene under the action of a catalyst and sodium nitrite to synthesize 4-bromine-2-fluorobiphenyl; carrying out grignard reaction and acidity reaction on the 4-bromine-2-fluorobiphenyl and 2-bromine sodium propionate under the action of a catalyst to generate 2-(2- fluorine-4-biphenylyl) propionic acid; condensing the 2-(2- fluorine-4-biphenylyl) propionic acid with 1-chloroacetic ethyl acetate to generate a target compound flurbiprofen axetil; and carrying out molecular distillation on the flurbiprofen axetil crude product to obtain a flurbiprofen axetil final product.

The invention discloses a method for preparing a flurbiprofen axetil compound. The method comprises the following steps: adding 1.0mol of 2-fluoro-alpha-methyl(1,1'-diphenyl)-4-acetic acid and 1L of solvent in a reaction container, stirring and heating to 70-75 DEG C, reacting for 2h, cooling to 20 DEG C, dropping 1.5-1.7mol of 1-bromoethyl acetate, reacting for 5h, and cooling; adding ethyl acetate and water, then separating out the organic phase, washing with water, washing with a saturated sodium carbonate solution, then washing with water, and finally washing with saturated salt water; and carrying out rotary evaporation on the organic phase to be dry, and vacuumizing to remove the solvent and obtain a crude product; and then dissolving the crude product with an organic solvent, adding silica gel and activated carbon, heating to reflux for 20-40min, cooling, performing suction filtering, and vacuumizing to obtain flurbiprofen axetil, wherein the solvent is N, N-dimethylformamide or potassium carbonate; and the organic solvent is a mixture of an ester solvent and an ether solvent, the volume ratio of the ester solvent to the ether solvent is 1:(5-30) and the addition amount of the organic solvent is 1-2 times that the mass of the crude product. By adopting the preparation method of the flurbiprofen axetil compound, the problems of the existing purification method can be well solved; the method has low cost, simpleness in operations and good product quality; and the quality of the product obtained through the experiment is higher than the import standard.

The invention relates to the field of pharmaceutical chemical synthesis, in particular to a preparation method of flurbiprofen and a preparation method of flurbiprofen axetil. The preparation method of the flurbiprofen comprises the steps of carrying out a Grignard reaction by using 4-bromine-2-fluorine biphenyl as a raw material, carrying out a coupling reaction, and acidizing to obtain the flurbiprofen; the yield is 90%, and the purity is 99.5%; then, the flurbiprofen axetil is prepared by using the flurbiprofen, obtained by the method, as a raw material, the yield reaches up to 90%, and thepurity reaches up to 99.5%. The preparation methods are high in quality controllability and industrial reproducibility.

The invention provides a flurbiprofen axetil microsphere preparation, a preparation method and an application thereof. The plurbiprofen axetil microsphere preparation comprises flurbiprofen axetil, an oil phase solvent and chitosan and/or derivatives thereof and an emulsifying agent. The method for preparing the flurbiprofen axetil microsphere preparation comprises the following steps of: (1) mixing oil phase mixture containing the flurbiprofen axetil, the oil phase solvent and the emulsifying agent so as to produce a uniform oil phase; (2) mixing aqueous phase mixture containing chitosan and/or the derivatives thereof and water so as to form a uniform aqueous phase; (3) adding the oil phase into the aqueous phase so as to form initial emulsion; and (4) homogenizing the initial emulsion. The invention further provides an application of the flurbiprofen axetil microsphere preparation to be used for preparing analgesic or anti-inflammatory drugs.

The invention relates to an ophthalmic flurbiprofen ester nano emulsion-in situ gel preparation and a preparation method thereof. The ophthalmic flurbiprofen ester nano-emulsion in situ gel preparation is made from oil, an emulsifier, a thickener, an osmoregulator, a bacteriostatic agent and purified water; and is characterized in that one or a plurality of safe and non-irritating lecithin, Tween60, Tween80, polyoxyethylene castor oil and polyoxyethylene hydrogenated castor oil are taken as the emulsifier; and a high molecular material with ion sensitivity characteristic is taken as the thickener. The ophthalmic flurbiprofen ester nano emulsion-in situ gel preparation is low-viscosity fluid with good fluidity in vitro, and rapidly forms hydrogel after being dropped in eyes. The ophthalmic flurbiprofen ester nano emulsion in-situ gel preparation has the advantages of increasing the residence time of the drug in eyes and increasing bioavailability, has no irritability or other toxic side effect to eyes, and has good biocompatibility and the like.

The invention provides anti-inflammatory and analgesic flurbiprofen axetil injection and a preparation method thereof. A mixture of 0.1-10 percent (w/v) of flurbiprofen axetil, 10-20 percent (w/v) of middle chain triglyceride (MCT) and 10-20 percent (w/v) of long chain triglyceride (LCT) is contained in the prescription (wherein the proportion of MCT and LCT is 4:1-1:4). The preparation method comprises the following steps: taking 1-5 percent (w/v) of lecithin as an emulsifying agent, taking 1-5 percent (w/v) of glycerol as an isotonic agent, finally adding disodium hydrogen phosphate, citric acid and water for injection and adjusting the pH value to 4-7 to prepare flurbiprofen axetil fat emulsion injection through colostrums, homogeneity and sterilization. The injection has the beneficial effects that the anti-inflammatory and analgesic effect is taken more quickly; the accumulation of fat of a human body can be reduced, and fatty tissues and liver load can be reduced; and the injection is more suitable for critically ill patients and people with poor liver functions and has lower toxic and side effects.

The invention relates to the use of (R)- flurbiprofenester in preparing medicament for analgesia and treatment of cancer and senile dementia, the invention also relates to a (R)-Flurbiprofen Axetil injection as main ingredient of the medicament, emulsifier of emulsibility constituents and solvent of soluble constituents. The invention also relates to the process for preparing the (R)-Flurbiprofen Axetil injection.

The invention provides a detection method of a related substance in flurbiprofen axetil injection. Two pairs of enantiomers and related substances thereof of the flurbiprofen axetil in the flurbiprofen axetil injection can be well separated by use of a reverse high performance liquid chromatography method after adopting gradient elution.

The invention provides a novel 2-(2-fluorine-4biphenyl)-propionic acid pharmaceutical composition. Flurbiprofen and basic amino acid arginine or lysine form a pharmaceutical composition solution. The composition can be administrated in an injection or oral administration manner and can also be further administrated in a freeze-drying manner. Compared with a flurbiprofen axetil injection, a flurbiprofen composition not only does not influence the antipyretic, anti-inflammation and analgestic effects of the flurbiprofen, but also has the advantages of simple technology, low cost, high quality, stable long shelf life and convenience in quality control, storage and transportation; moreover, compared with a conventional oral preparation, the flurbiprofen composition has the same low gastrointestinal tract adverse reaction as the flurbiprofen axetil injection.

The invention discloses application of a low-dosage esflurbiprofen axetil emulsion for injection. For the S (+) -flurbiprofen axetil emulsion for injection provided by the invention, when a certain curative effect is realized, the needed dosage of the S (+) -flurbiprofen axetil emulsion for injection is only 25%-75% of the dosage of the market flurbiprofen axetil emulsion, correspondingly, the clinic treatment dosage of the S (+) -flurbiprofen axetil emulsion for injection is 25%-75% of the market flurbiprofen axetil emulsion.

The invention discloses preparation methods of a flurbiprofen axetil compound. The methods comprise the steps: firstly dropwise adding an ester compound into a mixture of flurbiprofen, an acid catalyst and an organic solvent to form a reaction system, or directly mixing flurbiprofen, an alcohol and the acid catalyst, after a reaction is finished, thus obtaining a reaction system, then carrying out spin steaming concentration treatment under reduced pressure, adding ethyl acetate and water to fully dissolve, standing and layering to obtain an organic phase, washing the organic phase, drying, purifying by passing through a silica gel column, and thus obtaining the flurbiprofen axetil compound. The preparation methods have the advantages of simple reaction operation, low requirements on production personnel and production equipment, small pollution degree and low production cost, are safe and effective, can avoid use of high-risk and high-toxic materials, and can be used for mass production.

The invention discloses a flurbiprofen axetil micro-emulsion gel preparation and a preparation method thereof. The flurbiprofen axetil micro-emulsion gel preparation is characterized in that the preparation is composed of a gel substrate and a therapeutically effective amount of medicine-containing micro-emulsion loaded on the substrate. The preparation method provided by the invention has the advantages of simple process and easy operation. The prepared micro-emulsion gel preparation can be prepared into patches, such that a novel administration mode of flurbiprofen axetil is provided, and flurbiprofen axetil efficacy and application efficiency are improved.

The invention relates to the technical field of a medicine preparation, in particular to flurbiprofen axetil structure fat emulsion injection liquid and a preparation method thereof. The flurbiprofenaxetil structure fat emulsion injection liquid is prepared from flurbiprofen axetil, structure triglyceride, emulsifiers, lecithin, disodium hydrogen phosphate, glycerol, citric acid and injection water. The flurbiprofen axetil structure fat emulsion injection liquid provided by the invention has the advantages that the medicine effect is obvious; the toxic and side effects are lower; the stability is high.

The invention discloses a method for preparing S-(+)-flurbiprofen axetil high in optical purity.The method comprises the steps of 1, making S-(+)-flurbiprofen axetil react with 1-substituted ethyl acetate in the presence of alkali and organic solvent for 3-15 h at the temperature of 0-25 DEG C; 2, extracting and washing a reaction product, and separating out grease; 3, conducting column chromatographic purification on the grease; 4, removing organic solution residues with the solvent coevaporation method, and then conducting vacuum drying to obtain the target product.Inorganic base is not used, organic base highly intersoluble with organic solvent is adopted, a proper solvent ratio is selected to guarantee the proceeding of reaction, and racemization and product breakdown which occur often are avoided during preparation.The total yield of the prepared S-(+)-flurbiprofen axetil can be 80% or more, and optical purity is higher than 99%.

The invention relates to flurbiprofen axetil injection and a preparation method thereof and belongs to the technical field of pharmaceutic preparations. The flurbiprofen axetil injection contains flurbiprofen axetil and a cosolvent in a mole ratio of 1:(1-1.8), has the advantages of good solubility, stable quality and the like, can be used for avoiding drug-induced risks, probably caused by other products, of patients suffering from heart disease, hypertension and kidney disease and avoiding adverse effects such as nausea and stomachache.

The invention discloses a method for detecting related substances in a flurbiprofen axetil drug. A high performance liquid chromatography is adopted, and the mobile phase is a mixed solution of acetonitrile and water. According to the detection method provided by the invention, two pairs of enantiomers of flurbiprofen axetil and two pairs of enantiomers of defluorinated flurbiprofen axetil can beseparated synchronously.

The invention relates to an application of a flurbiprofen axetil pharmaceutical composition in preparing antipyretics. The flurbiprofen axetil pharmaceutical composition consists of flurbiprofen axetil, oil, egg yolk lecithin, glycerol, disodium hydrogen phosphate, citric acid and injection water, wherein the concentration of the flurbiprofen axetil is 0.1-10mg/ml, the concentration of the oil is 100mg/ml and the concentration of the egg yolk lecithin is 12mg/ml. The flurbiprofen axetil pharmaceutical composition disclosed by the invention can be used for relieving fever of a rat caused by dried yeast.

The invention provides a stable flurbiprofen axetil medicine composition which comprises flurbiprofen axetil with the weight/volume percent of 0.1-1% w/v, phosphatidyl choline with the weight/volume percent of 0.4-1.6% w/v, phosphatidyl ethanolamine with the weight/volume percent of smaller than or equal to 0.18% w/v, injection oil with the weight/volume percent of 10-30% w/v and injection water. The composition has good stability, the content of hydrolyzed impurity flurbiprofen is relatively low, and the shelf life of the composition is prolonged from 18 months to 24 months as compared with that of products sold in the market.