37 results about "Risedronic acid" patented technology

Provided is a novel method of making bisphosphonic acids, e.g. risedronic acid, including the step of combining a carboxylic acid, phoshorous acid, and a halophosphorous compound in the presence of a diluent that is an aromatic hydrocarbon or a silicone fluid. When the diluent is an aromatic hydrocarbon, a inert support or ortho-phosphoric acid codiluent is advantageously included.

Provided is a novel method of making bisphosphonic acids, e.g. risedronic acid, including the step of combining a carboxylic acid, phosphorous acid, and a halophosphorous compound in the presence of a diluent that is an aromatic hydrocarbon or a silicone fluid. When the diluent is an aromatic hydrocarbon, an inert support or ortho-phosphoric acid codiluent is advantageously included.

The invention relates to a method of determining risedronate in human plasma based on LC-MS / MS pre-derivatization. The pre-derivatization comprises steps: 150 muL of a plasma sample is taken, 5.00 muLof an internal standard working solution is added, uniform mixing is carried out, 150 muL of 10% trichloroacetic acid is added, after 3 min of oscillation, centrifugation for 5 min at 13,000 rpm is carried out, 100 muL of a supernatant is taken, 57.0 muL of methanol-25% ammonia water (50 to 7, v / v) is added, and 3 min of oscillation is carried out; and 400 muL of trimethylsilyl diazomethane is added, oscillatory derivation for 4 h at 1600 rpm is carried out, and after standing, 2.00 muL of a lower solution is taken for sampling. In comparison with the prior art, a derivative reaction is directly carried out after protein precipitation, the risedronate sample preprocessing process is greatly simplified, and the method has the advantages of short running time, good selectivity and high sensitivity.

Provided is a novel method of making bisphosphonic acids, e.g. risedronic acid, including the step of combining a carboxylic acid, phoshorous acid, and a halophosphorous compound in the presence of a diluent that is an aromatic hydrocarbon or a silicone fluid. When the diluent is an aromatic hydrocarbon, a inert support or ortho-phosphoric acid codiluent is advantageously included.

This process in general relates to the novel process for preparing polymorphic forms of 3-pyridyl-1-hydroxyethylidine-1,1-bisphosphonic acid sodium salt (Risedronate Sodium) in particular risedronate Form A and B employing a solvent system in an appropriate ratio. An improved process for preparation of risedronic acid is also disclosed in the present invention.

The present invention relates to a process for the preparation of bisphosphonic acids and salts thereof, in particular monosodium salts thereof. The invention also relates to the conversion of the bisphosphonic acids to their sodium salts using an aqueous-organic solvent system. The present invention further relates to the conversion of variable hydrate forms of risedronic acid monosodium salt into a pharmaceutically acceptable hemipentahydrate form by crystallization using an aqueous-organic solvent system.

A novel process for preparing risedronate sodium hemipentahydrate represented by the following formula 1 using 2-(3-pyridyl)-1-hydroxyethane-1,1-bisphosphonic acid (risedronic acid) and an aqueous solution of risedronate sodium is disclosed.

Disclosed are non-steroidal analgesic and analgesic anti-inflammatory agents containing carboxyl including sodium, calcium, zinc, magnesium, N-n-octylgucamine, Arginine, Lycine or Trometamol salts of Loxoprofen, Ketoprofen, Pranoprofen, Tiaprofenic acid, Butibufen, Omolofen, epoxy indene acid, Lobuprofen, Clofenamic acid, Clonixin, Fenoprofen, Benorilate, Flurbiprofen, Alminoprofen, Bucloxic acid, Sulindac, Zidometacin, Acemetacin, Ketorolac, Risedronic acid, Sulindac, Lonaprofen, aspirin, Florfenicol, tiaprofenic acid, overall evaluation shows that trometamol salts are the best choice in terms of physicochemical properties, solvability, stability, local irritation, blood vessel irritation, and bioavailability for oral administration.

The invention belongs to the technical field of medicines. Specifically, the invention relates to a risedronate zinc micro-nano adjuvant which is formed by mineralizing zinc ions and risedronate as main components and has a slow release function and application of the adjuvant in a vaccine adjuvant. The invention also relates to a preparation method of the risedronic acid micro-nano adjuvant. Theinvention also relates to a chemical composition, the vaccine adjuvant and a vaccine composition containing the risedronic acid micro-nano adjuvant. The invention also relates to application of the risedronic acid micro-nano adjuvant as the vaccine adjuvant.

The invention provides application of nitrogenous bisphosphonate combined glucocorticoid in prevention or treatment of viral pneumonia. In particular, the nitrogenous bisphosphonate combined glucocorticoid is used to treat or ameliorate coronavirus infections, wherein the nitrogen-containing bisphosphonate is selected from pamironate, alendronate, risedronate, ibandronate, zoledronate, minodronate and pnaphonate, and the glucocorticoid is selected from the group consisting of dexamethasone, rimesolone, prednisolone, fluorometholone, hydrocortisone, mometasone, fluticasone, beclomethasone, flunivoxone, antiphlogistic, fluticasone propionate, beclomethasone dipropionate, budesonide and mometasone furoate.

The present invention relates to a process for preparing risedronic acid comprising the step of combining a 3-pyridyl acetic acid or a salt thereof, phosphorous acid, and a halophosporous compound selected from PCl3, PClS, POCl3, PBr3, POBr3, and PBr5 in the presence of a diluent that is either a bicyclic aliphatic hydrocarbon or a substituted cyclic aliphatic hydrocarbon or a mixture thereof, in combination with a codiluent, that is orthophosphoric acid

The invention discloses a preparation method of risedronate sodium. The preparation method comprises the following steps of: (1) dissociating 3-pyridinecarboxylicacid chloride in 3-pyridinecarboxylicacid chloride hydrochloride; (2) reacting 3-pyridinecarboxylicacid chloride with diazomethane to generate a diazoketone compound represented by a formula (I); (3) generating 3-pyridylacetic acid under the common action of a catalyst and water; (4) adding hydrochloric acid, separating an organic phase from an inorganic phase, and evaporating and concentrating the inorganic phase to obtain 3-pyridylacetic acid hydrochloride; (5) converting 3-pyridylacetic acid hydrochloride into risedronic acid in the presence of phosphorus trichloride and phosphorous acid; and (6) reacting risedronic acid with sodium hydroxide solution to generate risedronate sodium. The preparation method of risedronate sodium disclosed by the invention has the advantages of being few in reaction step, short in reaction time, simple in post-treatment and higher in product yield.

The present invention pertains to the field of pharmaceutical technology. Specifically, the present invention relates to a zinc risedronate micro / nano adjuvant with sustained-release function formed by mineralization of zinc ions and risedronic acid as main components and its use as a vaccine adjuvant. The present invention also relates to a method for preparing zinc risedronate micro / nano adjuvant. The present invention also relates to a chemical composition, vaccine adjuvant and vaccine composition comprising zinc risedronate micro / nano adjuvant. The present invention also relates to a use of zinc risedronate micro / nano adjuvant as a vaccine adjuvant.

The invention provides application of nitrogen-containing bisphosphonates in prevention or treatment of viral pneumonia. In particular, the present regimen relates to new uses of nitrogen-containing bisphosphonates in the treatment or amelioration of coronavirus infection; wherein the nitrogen-containing bisphosphonate is selected from pamironate, alendronate, risedronate, ibandronate, zoledronate, minodronate and pnaphonate. The invention further discloses a preparation method of the nitrogen-containing bisphosphonate.

The invention provides a risedronic acid synthesized by a one-pot process. The risedronic acid is synthesized from 3-acetylpyridine as an initial material through Willgerodt-Kindle reaction, hydrolysis, diphosphonation and acidification employing the one-pot process. The risedronic acid has the advantages of being simple and convenient to operate, few in three wastes, mild and complete in reaction conditions, and suitable for industrial production, and has relatively high practical value; the reaction is finished in one container; the obtained product is stable in quality; and the purity can reach over 98%.

The disclosure provides a method for quantitatively determining risedronate in a urine sample by adding an internal standard to the urine sample, applying the urine sample to a polymeric water-wettable reverse-phased sorbent preconditioned with methanol, washing the sorbent with TEA in water and formic acid in methanol, eluting risedronate with a mixture of methanol and water containing EDTA under vacuum, evaporating the eluted solution and reconstituting with a mixture of methanol and NH4OH buffer and analyzing the sample with a LC-MS / MS system.

Disclosed in the present invention are a radiolabeled compound of a risedronic acid derivative, and a precursor compound thereof, and a preparation method therefor and the use, which belong to the technical field of nuclear medicine. Provided in the present invention are a precursor compound of a radiolabeled compound of a risedronic acid derivative as shown in formula (I) or a pharmaceutically acceptable salt thereof, and a radiolabeled compound of a risedronic acid derivative as shown in formula (II) or a pharmaceutically acceptable salt thereof. In the present invention, risedronic acid is creatively combined with a chelating agent to obtain NOTA-risedronic acid and DOTA-risedronic acid, and then a radionuclide is used for labelling. The radiolabeled product of the present invention has a relatively high water solubility, good in-vitro stability at room temperature, and a high plasma protein binding rate, and exhibits a relatively high and prolonged bone uptake in terms of imaging and in vivo distribution in mice; and compared to 68Ga-DOTA-ibandronic acid, the uptake of the compound of the present invention at the lesion site is twice as high.

An object of the present invention is to provide a preventive drug and a therapeutic drug for diseases caused by abnormal bone metabolism, especially osteoporosis, which is more effective than conventional drugs. Combined use of N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)phenoxy]pentoxy}-benzamidine, or a salt thereof; and at least one compound selected from the group consisting of etidronic acid, clodronic acid, pamidronic acid, tiludronic acid, risedronic acid, minodronic acid, ibandronic acid, zoledronic acid, and salts thereof can exert higher bone resorption inhibitory effect and provide a preventive effect and a therapeutic effect for diseases caused by abnormal bone metabolism, especially osteoporosis as compared with administration of the respective agents respectively.

The present invention provides a pharmaceutical composition for preventing or treating osteoporosis, comprising risedronic acid or a salt thereof and vitamin D. Further, the present invention provides an oral tablet obtained by tableting a mixture of risedronic acid or a salt thereof and granular vitamin D; and an oral capsule obtained by uniformly distributing risedronic acid or a salt thereof and vitamin D among the mixed solvent of soybean oil and hydrogenated coconut palm oil and filling a capsule with the resultant material.

It is intended to provide a preventive agent or a therapeutic agent for a disease caused by abnormal bone metabolism, particularly for osteoporosis, which is more effective than ever before. By combined application of N-hydroxy-4-{5-[4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenoxy]pentoxy}-benzamidine or a salt thereof and one or more compounds selected from the group consisting of etidronic acid, clodronic acid, pamidronic acid, tiludronic acid, risedronic acid, minodronic acid, ibandronic acid, zoledronic acid, and salts thereof, a higher bone resorption inhibitory action compared with the administration of a single compound is exhibited, and an excellent preventive effect and therapeutic effect for a disease caused by abnormal bone metabolism, particularly for osteoporosis can be obtained.

The invention provides a risedronic acid synthesized by a one-pot process. The risedronic acid is synthesized from 3-acetylpyridine as an initial material through Willgerodt-Kindle reaction, hydrolysis, diphosphonation and acidification employing the one-pot process. The risedronic acid has the advantages of being simple and convenient to operate, few in three wastes, mild and complete in reaction conditions, and suitable for industrial production, and has relatively high practical value; the reaction is finished in one container; the obtained product is stable in quality; and the purity can reach over 98%.

The invention discloses a radioactive marker of a dithiophosphoric acid derivative, a precursor compound of the radioactive marker, a preparation method of the radioactive marker and application of the radioactive marker, and belongs to the technical field of nuclear medicine. The invention provides a precursor compound of a radiomarker of a dithiophosphoric acid derivative as shown in a structural formula (I) or a pharmaceutically acceptable salt of the precursor compound, and a radiomarker of a dithiophosphoric acid derivative as shown in a formula (II) or a pharmaceutically acceptable salt of the radiomarker. According to the invention, risedronic acid is creatively combined with a chelating agent to obtain NOTA-risedronic acid and DOTA-risedronic acid, and then radionuclides are used for labeling. The radiolabeled product disclosed by the invention is relatively high in water solubility, relatively good in-vitro stability at room temperature and high in plasma protein binding rate, and relatively high and relatively long-lasting skeleton uptake is shown in imaging and in-vivo distribution in mice; and compared with the 68Ga-DOTA-ibandronic acid, the intake of the compound disclosed by the invention at the focus part is twice of that of the 68Ga-DOTA-ibandronic acid.

The invention discloses a risedronate calcium complex and a preparation method thereof, the chemical formula of the risedronate calcium complex is Ca (Ris) (H2O), Ca represents calcium, Ris represents risedronate, H2O represents water, the crystal system is an orthorhombic system, the space group is P212121, and the lattice constant z is 4. The preparation method comprises the following steps: by taking calcium salt and risedronate or risedronate sodium as raw materials and deionized water as a solvent, adjusting the pH value to 3-7 by using a sodium hydroxide solution, standing at 20-200 DEG C for 12-72 hours, filtering, washing and drying to obtain a strip-shaped transparent crystal, namely the risedronate calcium complex. The preparation method disclosed by the invention is extremely simple, moderate in crystal growth speed, small in stress, good in uniformity and very complete in appearance, and has important potential application prospects in the fields of drug sustained release, targeted delivery, bone tissue repair and the like.

The invention relates to an adjuvant containing zinc aluminum risedronate, an immunogenic composition containing the adjuvant and an immunogen, and application of the adjuvant and the immunogenic composition.

The invention discloses a preparation method of risedronate sodium. The preparation method comprises the following steps of: (1) dissociating 3-pyridinecarboxylicacid chloride in 3-pyridinecarboxylicacid chloride hydrochloride; (2) reacting 3-pyridinecarboxylicacid chloride with diazomethane to generate a diazoketone compound represented by a formula (I); (3) generating 3-pyridylacetic acid under the common action of a catalyst and water; (4) adding hydrochloric acid, separating an organic phase from an inorganic phase, and evaporating and concentrating the inorganic phase to obtain 3-pyridylacetic acid hydrochloride; (5) converting 3-pyridylacetic acid hydrochloride into risedronic acid in the presence of phosphorus trichloride and phosphorous acid; and (6) reacting risedronic acid with sodium hydroxide solution to generate risedronate sodium. The preparation method of risedronate sodium disclosed by the invention has the advantages of being few in reaction step, short in reaction time, simple in post-treatment and higher in product yield.

The invention discloses a preparation method and application of an RS-HAP composite material, the RS-HAP composite material is risedronate nano-functionalized hydroxyapatite, and the risedronate nano-functionalized hydroxyapatite is prepared by adopting risedronate sodium, diammonium hydrogen phosphate and calcium chloride as raw materials. The risedronate and the hydroxyapatite are tightly combined through a coprecipitation method by utilizing the excellent chelation effect of the risedronate on cations, so that the problem of loose reactant combination in traditional physical mixing or modification is effectively avoided. Meanwhile, the adsorption performance of RS-HAP on heavy metal ions such as Pb < 2 + > and Co < 2 + > is greatly improved through the strong chelating capacity of oxygen atoms of a risedronate phosphonite group on cations, and the breakthrough improvement of the adsorption performance of traditional HAP is achieved; the adsorbent has the advantages of large adsorption capacity, high adsorption efficiency, simple and controllable preparation process, stable material structure, wide application scene, excellent regeneration performance and the like.

The invention discloses an application of masitinib, C22H17N3 and risedronic acid in preparation of a medicine for treating enterovirus infection. The invention discloses masitinib, C22H17N3, risedronic acid or derivatives thereof or pharmaceutically acceptable salts thereof or prodrugs thereof, or any one of the following applications of substances taking masitinib, C22H17N3, risedronic acid or derivatives thereof or pharmaceutically acceptable salts thereof as active ingredients in preparation of drugs for inhibiting enteroviruses; a2) a medicine for preventing and / or treating diseases caused by enterovirus infection; and A3) a medicine for improving symptoms caused by enterovirus infection. On the basis of an enterovirus type 71 and / or coxsackie virus drug screening model, an active drug masitinib capable of resisting enterovirus type 71, coxsackie virus group A type 9 and / or coxsackie virus group B type 3 is screened from listed drugs, and effect verification is carried out on a type 1 poliovirus model and / or an echovirus type 11 model.