30 results about "Bromfenac sodium" patented technology

The invention relates to a bromfenac sodium preparation method. The preparation method comprises specific steps as follows: indole reacts under the action of DMSO (dimethylsulfoxide) to produce 3-bromoindole; 3-bromoindole is added to 2-methoxyethanol, acid is added for hydrolysis, and 2-indolinone is obtained; boron trichloride is added to methylbenzene, a methylbenzene mixed solution of p-bromobenzonitrile and 2-indolinone is added dropwise, aluminum chloride is then added, acid is added, a reaction is performed, and 7-(4-bromobenzoyl)-1,3-dihydro-indol-2-one is obtained; hydrolysis is performed with an alkaline solution, acid is added for neutralization, and bromfenac is obtained; ethanol is added to bromfenac, bromfenac and a sodium hydroxide solution form salt, the salt is cooled and subjected to recrystallization, and bromfenac sodium is obtained. Compared with the prior art, the synthetic route is short, high-purity bromfenac sodium can be prepared, the quality meets the latest standards of pharmacopoeia, industrial production is facilitated, and the method can provide powerful guarantee for industrial production of bromfenac sodium and intermediates of bromfenac sodium.

The invention provides a preparation and refining method of bromfenac sodium. The method has the advantages that the reaction conditions are mild, the operation is simple, and the obtained product is high in purity, high in yield and low in cost and can be industrially produced easily.

The invention relates to an ophthalmic gel containing the active ingredient of bromfenac sodium hydrate and a preparation method thereof; the bromfenac sodium hydrate ophthalmic gel contains the active ingredient of bromfenac sodium hydrate, macromolecular hydrogel substrate, osmotic pressure regulator, bacteriostat, antioxidant, metal ion chelating agent, pH regulator and water for injection; the ophthalmic gel has convenient application and quick effect; particularly, the gel possesses certain viscosity and can stay in the eyes for a long time, thus overcoming the defect that eye drops can only stay in the eyes for a short time after being diluted by tears and achieving more effective therapeutic effect.

The invention discloses bromfenac sodium hydrate thermosensitive in-situ gel eye drops which comprise, by weight, 0.05%-0.15% of active component bromfenac sodium hydrates, 1%-30% of themosensitive gel materials and auxiliary materials acceptable in pharmacy; the pH value of the eye drops is regulated to 6.5-9.0, and the osmotic pressure is set at 286-310 mOsmol/k. The invention further provides a preparation method of the bromfenac sodium hydrate thermosensitive in-situ gel eye drops. Compared with the prior art, the bromfenac sodium hydrate thermosensitive in-situ gel eye drops and the preparation method thereof have the advantages that the problems that traditional eye drops are short in stay time in the eyes and low in bioavailability are solved, the defects that the viscosity of traditional eye gel is high and transfer in the producing and using process is difficult are overcome, and the compliance of a patient is improved.

The invention discloses a method for synthesizing bromfenac sodium. The method comprises the steps of (1) carrying out acetylation reaction on 2-amino-4'-bromo benzophenone as a raw material to obtain a formula III: N-(2-(4'-bromo benzoyl)phenyl)acetamide; (2) reacting the N-(2-(4'-bromo benzoyl)phenyl)acetamide in a formula IV with a halogen acetylation reagent to obtain a formula V: N-acetyl-N-(2-(4'-bromo benzoyl)phenyl)-2-haloacetamide; (3) carrying out friedel-crafts reaction on the N-acetyl-N-(2-(4'-bromo benzoyl)phenyl)-2-haloacetamide to obtain a formula IV: 1-acetyl-7-(4-bromo-benzoyl chloride) indoline-2-ketone; and (4) finally hydrolyzing the 1-acetyl-7-(4-bromo-benzoyl chloride) indoline-2-ketone to obtain a target product. The method is low in cost, reaction is easy to control, post-treatment is simple, the overall yield is high, the method is economical and environmentally friendly, and a novel method for synthesizing the bromfenac sodium is provided.

Belonging to the technical field of drug detection, the invention in particular relates to a determination method for related substances of Bromfenac sodium eye drops. The determination method includes the specific steps of: adopting an octadecyl silane bonded silica gel column or Lycopodine N-oxide M bonded silica gel column, and taking a phosphate buffer solution-acetonitrile as the mobile phase to conduct gradient elution, and setting the detection wavelength at 250-280nm, the column temperature at 10-30DEG C, the flow rate at 0.8-3ml/min, and a sample size of 20-70 microliter. Compared with the prior art, the determination method for related substances of Bromfenac sodium eye drops provided by the invention realizes separation and analysis of Bromfenac sodium and its related substances, and has the characteristics of good separation degree, strong specificity and high sensitivity, and can quantitate the three known impurities by self-control method without correction factor. The determination method has important practical significance for the quality control of Bromfenac sodium eye drops.

Different polymorphs of bromfenac sodium may be prepared and interconverted using crystallization/recrystallization, drying and/or hydration techniques.

The invention belongs to the technical field of medicine, and provides a preparation method of a bromfenac sodium dimer impurity, which comprises the following steps: hydrolyzing 7-(4-bromobenzoyl)-1,3-dihydro-indolyl-2-one to obtain bromfenac, adding bromfenac into an alkali metal hydroxide solution, crystallizing to obtain a bromfenac sodium dimer impurity crude product, and adding the bromfenac sodium dimer impurity crude product into ethyl acetate to obtain the bromfenac sodium dimer impurity. The method can precipitate the impurity in the bromfenac sodium dimer impurity crude product by salification, simply and efficiently implements refinement and purification of the bromfenac sodium dimer impurity, enhances the purity to 99% above, is simple and convenient, and has the advantages of favorable environmental benefit and high yield.

The invention aims at providing a preparation method of bromfenac sodium sesquihydrate. The preparation method comprises the following steps: (1) adding bromfenac sodium and an antioxidant into a mixed solvent of water and an organic alcohol, heating, dissolving and adding a pH adjustor to adjust the pH to 7.0-10.5; (2) adding an anti-solvent into a solution obtained in the step (1), cooling the solution to 30 DEG C to 35 DEG C, adding bromfenac sodium monohydrate, bromfenac sodium sesquihydrate or a mixture thereof as a seed crystal, and stirring; and (3) cooling, crystallizing, collecting crystals and drying to obtain the bromfenac sodium sesquihydrate. The preparation method avoids use of ether agents and is mild in reaction condition and good in environmental benefit. The prepared bromfenac sodium sesquihydrate is high in purity.

The invention relates to an ophthalmic pharmaceutical preparation for treating conjunctivitis, scleritis and eye postoperative inflammations, in particular to a sustained-release bromfenac sodium ophthalmic preparation. The sustained-release bromfenac sodium ophthalmic preparation provided by the invention is prepared from bromfenac sodium, carthamin yellow, sodium hyaluronate and a pharmacologically acceptable carrier. The sustained-release bromfenac sodium ophthalmic preparation provided by the invention has the advantages of good intraocular penetrability, high intraocular bioavailability,high penetration, high targeting effect, small toxic and side effects and the like, and is suitable for treating inflammatory eye diseases and used for treating conjunctivitis, scleritis and eye postoperative infection.

The invention discloses a preparation method of bromfenac sodium. O-ethylaniline and p-bromobenzoyl chloride are used as initiators and a series of reactions of Fourier reaction, substitution and oxidation salification are carried out, so that bromfenac sodium is obtained. The method has the advantages that the process is simple, post-treatment is simple and convenient, dangerous catalytic hydrogenation is avoided, the use of a strong corrosive reagent of phosphoric acid is avoided, the reaction condition is mild, the reaction yield is high, the product quality is high, the process cost is low, and the method is green and energy-saving.

The invention discloses a synthesis method of a bromfenac sodium impurity standard substance 2-amino-3-(4-bromo benzoyl) benzoic acid. 7-(4-Bromobenzoyl)indoline-2,3-dione is taken as a material, the operations of decarboxylation and refining are carried out to prepare a pure product of 2-amino-3-(4-bromo benzoyl) benzoic acid, and the content of the pure product is calibrated through a conventional analysis means. The impurity preparation method provided by the invention is simple and convenient in process and short in preparation period, and calibration shows that the product content is higher than 99.0%. The bromfenac sodium impurity provided by the invention can serve as the impurity standard substance, and is applied to qualitative and quantitative researches and detection of the bromfenac sodium material and the preparation impurity.

The invention discloses a synthesis method of bromfenac sodium. The preparation method comprises the following steps: firstly, by taking o-aminobenzoic acid as a raw material, adding a solvent, alkali and a fluorenylmethoxycarbonyl chloride isopropyl ether solution to react, and treating after the reaction to obtain 2-(9-fluorenylmethoxycarbonyl amino) benzoic acid; adding a solvent and strongly acidic cationic resin into the obtained product for reaction, and treating after the reaction to obtain 2-(9-fluorenylmethoxycarbonyl amino) ethyl benzoate; then a solvent, 4-bromobenzoyl chloride and a catalyst are added for a reaction, and 3-(4-bromo-benzoyl)-2-(9-fluorenylmethoxycarbonyl amino)-ethyl benzoate is obtained through treatment after the reaction; adding a solvent and a sodium hydroxide aqueous solution into the obtained product for reaction and treatment to obtain a bromfenac sodium crude product; and finally, refining the obtained bromfenac sodium crude product to obtain a bromfenac sodium product. The preparation method has the advantages of easily available raw materials, mild reaction conditions and high purity of the prepared finished product, and is suitable for industrial production.

The invention provides a pharmaceutical composition of bromfenac sodium, which comprises the following components in percentage by weight: 0.01-0.5% of bromfenac sodium sesquihydrate and pharmacologically acceptable salt thereof; 0.01%-1% by weight of a viscosity modifier dextran; 0.01%-1% by weight of a surfactant; and 0.01%-0.5% by weight of an antioxidant; and optional other auxiliary materialsacceptable in pharmacology. The bromfenac sodium eye drops have the beneficial effects that when the bromfenac sodium eye drops contain dextran 40 or dextran 70, impurities U-II can be effectively prevented from being generated, and the condition that the addition of dextran can also ensure the antibacterial effect of benzalkonium chloride, prolong the intraocular residence time and improve the drug effect can be accidentally found.

The invention discloses a method for preparing bromfenac sodium and relates to the technical field of medicinal chemical industry. The method comprises the following steps: adding 7-(4-bromobenzoyl)-1,3-dihydro-2H-indolyl-2-one and sodium hydroxide into a monoalcohol-deionized water system, carrying out a closed stirred reaction for 3 to 5 hours at the temperature of 90 DEG C to 110 DEG C, carrying out cooling, dropwise adding hydrochloric acid to adjust pH, adding a decolorant, carrying out refluxing-stirring decolorization under atmospheric pressure, carrying out filtering while the solutionis hot, and carrying out crystallization and drying, thereby obtaining bromfenac sodium. According to the method, the monoalcohol-deionized water system serves as a reaction solvent and replaces mixed solvents of water-soluble organic solvents/water-insoluble organic solvents in the prior art such as toluene/ethanol and dichloromethane/ethanol; through changing a solvent system of a bromfenac sodium synthesis reaction, process operations are simplified, and the product yield is increased; a decolorization process is integrated into a reaction aftertreatment process, so that the product purityis improved while decolorization is carried out, the production cost is reduced, and the product purity can reach 100% through HPLC measurement; and the reaction solvent can be recycled, and the harmless treatment cost of the solvent is low.