30 results about "Diflunisal" patented technology

The invention discloses a diflunisal solid dispersion and a preparation method thereof. The solid dispersion is composed of diflunisal as active components and high-polymer carrier materials. The high-polymer carrier materials are 40-90% of the diflunisal in total and selected from povidones, copovidones, and polyethylene glycol / vinyl caprolactam / vinyl acetate copolymer or hydroxypropyl methylcellulose. The preparation method adopts a hot-melting extrusion method. The diflunisal solid dispersion obtained is higher in solubility and quick and high in dissolving, bioavailability of indissolvable drugs is improved, drug dosage is reduced, and adverse drug reaction is reduced.

The administration to a mammal of a combination of compounds, at least one of which is an a2d calcium channel subunit (A2d) ligand and at least one of which is a non-steroidal anti-inflammatory drug (NSAID), provides a surprising and potent inhibition of the micturition reflex, superior to that obtained by treatment with an A2d ligand or NSAID alone. Combinations of A2d ligand and NSAIDs are thus useful for treatment of lower urinary tract disorders and symptoms thereof. Preferred A2d ligands are gabapentin and pregabalin. Preferred NSAIDs are celecoxib, diclofenac, diflunisal, flurbiprofen, naproxen, nimesulide or sulindac.

The invention provides a method for synthesizing a biphenylcarboxylic acid compound by using the Suzuki coupling reaction. According to the method, brominated aromatic hydrocarbon and arylboronic acidare used as raw materials, and water-soluble fullerene nanopalladium is used as a catalyst; and the equation of the Suzuki coupling reaction is as described in the specification. In the equation, R1and R2 represent substituents at different positions, may be acceptor or donor substituents, and may be monosubstitutents or polysubstitutent; and R1 and R2 may be identical or different groups. The water-soluble fullerene nanopalladium catalyst is cheap, easily available and environmentally friendly, and has high catalytic activity and stable properties. When the catalyst is used for catalysis ofthe Suzuki coupling reaction, conditions are mild, anhydrous anaerobic treatment and high-temperature treatment are not needed, and cost is low. The method can be applied to the industrial synthesisof non-steroidal anti-inflammatory drugs such as diphenylacetic acid and diflunisal.

O-medium alkyl esters of diflunisal and related compounds are disclosed having anti-platelet activity, hydroxy radical scavenging properties, enhanced hepatic clearance and low ulcerogenic potential. These compounds have general formula (I) wherein n equals 3-13.

The invention relates to a self-assembly system based on hydrophilic polymer and medicine and a preparation method thereof. The system consists of a hydrophilic polymer and a carboxyl-containing medicine, wherein the hydrophilic polymer is polymine or beta-cyclodextrin modified polymine; and the carboxyl-containing medicine is selected from ibuprofen, ketoprofen, fenoprofen, flurbiprofene, oxaprozin, naproxen, indometacin, sulindac, etodolac, diclofenac, pontal, meclofenamic acid, flufenamic acid, tolfenamic acid, lumiracoxib, licofelone, diflunisal and aspirin. The system is prepared by dissolving the hydrophilic polymer in a certain amount of water, dissolving the medicine in a water soluble solvent, slowly adding the organic solution of the medicine into the aqueous solution of the polymer under the action of ultrasound, placing the mixed solution in a dialysis bag, dialyzing in deionized water with magnetic stirring, replacing the deionized water at certain time interval, filtering dislysate after 5 to 48 hours, cooling and drying.

The invention belongs to the chemical pharmaceutical technical field and in particular relates to an eutectic medicine of 2 ',4 '- difluoro-4-hydroxyl-3-biphenyl carboxylic acid and pyridine carboxamide compounds and a preparation method thereof. The eutectic medicine prepared in the invention is obviously improved in solubility.

Disclosed is a method of quantum dot-labeled indirect competitive fluorescence immunoassay of diflucortolone, which belongs to the immunoassay method technique field. Quantum dots for labeling antibodies of the invention have the emission spectra of QD650, and the method comprises: directly covering coating antigens in micro-holes of an enzyme label plate, adding diflucortolone standard solution or a sample under test to form an antigen-antibody fluorescence immunity compound body, stimulating and detecting the fluorescence intensity of the formed antigen-antibody fluorescence immunity compound body with a fluorescence enzyme-labeling instrument, and obtaining the concentration of diflucortolone in the sample under test through comparing with the standard solution. The invention can detect the content of diflucortolone in the sample under test without adding chromogenic substance, namely, the concentration of diflucortolone in the sample under test can be detected indirectly through the fluorescence intensity of the antigen-antibody immunity compound body, and both the operation and reaction need only one step; and the quantum dots for labeling antibodies of the invention have advantages of stronger emitted fluorescence intensity and long stabilization time of fluorescence compared with the traditional fluorescence.

The invention discloses a diflunisal pharmaceutical composition and medical application thereof. The diflunisal pharmaceutical composition provided by the invention contains diflunisal and a natural product compound (I) novel in structure, when diflunisal and the compound (I) independently affect, CD4<+> cell number and immunologic function can be improved, immunologic balance can be adjusted, and therapeutical effect on Aids is realized; and when diflunisal and the compound (I) jointly act, the therapeutical effect is further improved, a medicine for treating the Aids can be developed, and prominent substantiality characteristic and obvious progress are realized compared with the prior art.

Relating to the field of organic synthesis, the invention discloses a method for one-step synthesis of non-steroidal anti-inflammatory drug diflunisal. The method includes: controlling the charging sequence, taking 2, 4-difluorophenylboronic acid and 5-bromosalicylic acid as the raw materials, taking a mixed solution of an aqueous phase and an organic solvent as the solvent, conducting ligand-freepalladium catalysis in the presence of an alkali metal salt, carrying out catalytic reaction under the ultrasonic condition of 70-80DEG C for 90-110min for one-step synthesis of a diflunisal crude product, and further conducting refining to obtain the diflunisal product with yield of 98.37% and purity of 99.89%. The method has the characteristics of green and high efficiency, mild reaction conditions, simple and safe process, and the obtained product has high yield and good purity, and has important industrial prospects.

This invention is directed to pharmaceutical combinations comprising an antioxidant agent, an anti-inflammatory agent, and optionally at least one other anti-diabetic agent useful for treating metabolic disorders. This invention also encompasses pharmaceutically acceptable compositions comprising an antioxidant agent, an anti-inflammatory agent, optionally at least one other anti-diabetic agent, and at least one pharmaceutically acceptable carrier. The combinations and compositions of this invention are useful as methods for treating metabolic disorders including diabetes, particularly Type I and Type II diabetes, as well as diseases and disorders associated with diabetes, including but not limited to atherosclerosis, cardiovascular disease, inflammatory disorders, nephropathy, neuropathy, retinopathy, β-cell dysfunction, dyslipidemia, LADA, metabolic syndrome, hyperglycemia, insulin resistance, and / or chronic obstructive pulmonary disease in a mammal, particularly a diabetic mammal, and specifically a human patient. This invention is particularly directed to pharmaceutical compositions comprising an lipoic acid, one or more anti-inflammatories selected from the group consisting of diflunisal, diclofenac, dexibuprofen, dexketoprofen, naproxen, and salicylate, and optionally one or more pharmaceutically acceptable carriers. The compositions of this invention are useful as methods for treating metabolic disorders including type II diabetes, insulin resistance, beta-cell dysfunction, and hyperglycemia in a patient, particularly a diabetic patient.

The invention discloses a diflunisal solid dispersion and a preparation method thereof. The solid dispersion is composed of diflunisal as active components and high-polymer carrier materials. The high-polymer carrier materials are 40-90% of the diflunisal in total and selected from povidones, copovidones, and polyethylene glycol / vinyl caprolactam / vinyl acetate copolymer or hydroxypropyl methylcellulose. The preparation method adopts a hot-melting extrusion method. The diflunisal solid dispersion obtained is higher in solubility and quick and high in dissolving, bioavailability of indissolvable drugs is improved, drug dosage is reduced, and adverse drug reaction is reduced.

The invention aims to provide application of diflunisal in preparation of a drug for preventing and treating diabetes. The diflunisal is used as an effective component in the drug for preventing and treating the diabetes. The concentration of the diflunisal in the drug for preventing and treating the diabetes is 40 to 80 [mu]M. The diflunisal can be well applied to the drug for preventing and treating the diabetes, particularly type II diabetes; the diflunisal can obviously improve insulin resistance and improve the absorption of hepatic cells under insulin resistance for glucose; the effect is outstanding; the aim of preventing and improving the diabetic condition is achieved.

The present invention relates to novel positively charged diflunisal, salicyl salicylic acid and prodrugs of salicylic acid shown in general formula (1) "structural formula 1" and general formula (2) "structural formula 2" design and synthesis. The compounds in the above general formula (1) "structural formula 1" and general formula (2) "structural formula 2" can be prepared by reacting diflunisal, salicyl salicylic acid or salicylic acid with appropriate alcohols, mercaptans, or amines have to. These prodrugs can be used medicinally in the treatment of any diflunisal, salicylsalicylic acid or salicylic acid treatable state in humans or animals, not only by oral administration but also by transdermal administration in the treatment, thereby avoiding the Most side effects of diflunisal, salicylsalicylic acid, or salicylic acid were eliminated. The controlled-release transdermal drug delivery system of the prodrug can stabilize the blood drug concentration of diflunisal, salicylsalicylic acid or salicylic acid at the optimal therapeutic level, thereby improving the curative effect and reducing diflunisal, salicylsalicylic acid or salicylic acid. Salicylic acid side effects.

The invention discloses a method for synthetizing diflunisal and a derivative thereof through a one-step method. The method comprises the steps: under joint catalysis of an iron salt, a ligand and titanate, 2,4-difluorophenylmagnesium halide and 5-halogenated salicylic acid or a 5-halogenated salicylic acid derivative are mixed, heated and coupled in a solvent, and the diflunisal and the derivative thereof are obtained. The method has the advantages that (1) high-priced palladium or high-toxicity nickel does not need to be adopted as catalytic metal, only low-toxicity, high-yield and inexpensive iron salts and titanate need to be used, thus the cost is low, and environmental friendliness is achieved; (2) a zinc salt does not need to be used, or step preparation of a boron reagent is not needed, a Grignard reagent is directly used, the preparation steps are few, and raw material and energy consumption is low; and (3) operation is easy and convenient, conditions are mild, amplification is easy, and the method is suitable for industrial production.

The novel positively charged pro-drugs of diflunisal, salicylsalicylic acid, and salicylic acid in the general formula(1) 'Structure 1' and general formula(2) 'Structure 2' were designed and synthesized. The compounds of the general formula(1) 'Structure 1' or general formula(2) 'Structure 2' indicated above can be prepared from functional derivatives of diflunisal, salicylsalicylic acid, or salicylic acid, (for example acid halides or mixed anhydrides), by reaction with suitable alcohols, thiols, or amines. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The results suggest that the pro-drug, diethylaminoethyl 5-(2,4-difluorophenyl) salicylate. AcOH diffuses through human skin ~150 times faster than does diflunisal itself. In plasma, more than 90% of these pro-drugs can change back to the drug in a few minutes. The prodrugs can be used medicinally in treating any diflunisal, salicylsalicylic acid, or salicylic acid-treatable conditions in humans or animals and be administered not only orally, but also transdermally for any kind of medical treatments and avoid most of the side effects of diflunisal, salicylsalicylic acid, or salicylic acid, most notably GI disturbances such as dyspepsia, gastroduodenal bleeding, gastric ulcerations, and gastritis. Controlled transdermal administration systems of the prodrug enables diflunisal, salicylsalicylic acid, or salicylic acid to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of diflunisal, salicylsalicylic acid, or salicylic acid.

The present invention provides a fluorine benzene ruthenium compound and a preparation method and application thereof. The structure of the fluorine benzene ruthenium compound is shown in formula (I). The fluorine benzene ruthenium compound is synthesized and generated by dichloridized dichloro-2-methyl-isopropyl-benzo dirhodium and phenylacetyl diflunisal and shows a relatively strong inhibition activity on a human lymph cancer cell strain and a liver cancer strain of a human body. The fluorine benzene ruthenium compound can be used for preparing medicines for treating liver cancer and lymph cancer, and can be prepared to injections, tablets, pellets, capsules, suspensions or emulsions. The fluorine benzene ruthenium compound provided by the invention can improve the lipid solubility and the permeability of medicines, enhances the dissolubility of a biological film and prompts the speed of absorption and transmission in vivo, so that the physiological action changes.

The invention discloses a method for synthetizing diflunisal and a derivative thereof through a one-step method. The method comprises the steps: under joint catalysis of an iron salt, a ligand and titanate, 2,4-difluorophenylmagnesium halide and 5-halogenated salicylic acid or a 5-halogenated salicylic acid derivative are mixed, heated and coupled in a solvent, and the diflunisal and the derivative thereof are obtained. The method has the advantages that (1) high-priced palladium or high-toxicity nickel does not need to be adopted as catalytic metal, only low-toxicity, high-yield and inexpensive iron salts and titanate need to be used, thus the cost is low, and environmental friendliness is achieved; (2) a zinc salt does not need to be used, or step preparation of a boron reagent is not needed, a Grignard reagent is directly used, the preparation steps are few, and raw material and energy consumption is low; and (3) operation is easy and convenient, conditions are mild, amplification is easy, and the method is suitable for industrial production.

The present invention relates to design and synthesis of a novel prodrug of diflunisal, salsalate, and salicylic acid, wherein the prodrug is positively charged, and has a structural formula 1 as shown in the general formula (1), and a structural formula 2 as shown in the general formula (2). The compound with the structural formula 1 as shown in the general formula (1), and the structural formula 2 as shown in the general formula (2) can be prepared by a reaction of diflunisal, salsalate and salicylic acid with appropriate alcohol, mercaptan, or amine. The prodrugs can be used in medicine for the therapy of humans or animals in a state that can be treated with diflunisal, salsalate, or salicylic acid, and in the therapy process, the prodrugs can be orally used, and can be transdermally administrated, so that the most side effects of the diflunisal, salsalate, or salicylic acid are avoided. According to a controlled release transdermal administration system of the prodrug, the concentration of the diflunisal, salsalate, or salicylic acid in blood can be kept stable in the optimal therapy proficiency, so that the efficacy is improved, and the side effects of the diflunisal, salsalate, or salicylic acid are reduced.

The invention relates to a self-assembly system based on hydrophilic polymer and medicine and a preparation method thereof. The system consists of a hydrophilic polymer and a carboxyl-containing medicine, wherein the hydrophilic polymer is polymine or beta-cyclodextrin modified polymine; and the carboxyl-containing medicine is selected from ibuprofen, ketoprofen, fenoprofen, flurbiprofene, oxaprozin, naproxen, indometacin, sulindac, etodolac, diclofenac, pontal, meclofenamic acid, flufenamic acid, tolfenamic acid, lumiracoxib, licofelone, diflunisal and aspirin. The system is prepared by dissolving the hydrophilic polymer in a certain amount of water, dissolving the medicine in a water soluble solvent, slowly adding the organic solution of the medicine into the aqueous solution of the polymer under the action of ultrasound, placing the mixed solution in a dialysis bag, dialyzing in deionized water with magnetic stirring, replacing the deionized water at certain time interval, filtering dislysate after 5 to 48 hours, cooling and drying.