281 results about "Atorvastatin calcium" patented technology

The invention relates to a process for the preparation of amorphous atorvastatin calcium by recrystallization of crude atorvastatin from an organic solvent which comprises dissolving crude amorphous atorvastatin calcium in a lower alkanol containing 2-4 carbon atoms or a mixture of such alkanols under heating and isolating the amorphous atorvastatin calcium precipitated after cooling. The atorvastatin calcium obtained is a known valuable agent useful in treating hyperlipidemia and hypercholestrolemia.

The invention which relates to an atorvastatin calcium tablet for treating hyperlipidemia belongs to the technical field of western medicine preparations. In the tablet, the weight ratio of atorvastatin calcium: a filler: a disintegrant: a lubricant is 1:8-15:0.5-1.5:0.1-0.3. The tablet of the present invention has the advantages of stable quality, rapid disintegration and leaching, moderate tablet hardness, and simple preparation technology.

The invention relates to atorvastatin calcium tablets and a preparation method thereof. The tablets comprise the following components in parts by weight: 1 part of atorvastatin calcium (in terms of atorvastatin), 1 part of croscarmellose sodium, 15 parts of lactose (80M), and 0.2 part of magnesium stearate. The preparation method comprises the following steps: screening the atorvastatin calcium and the croscarmellose sodium based on the amounts of the formula through a 120-meshed sieve respectively, and mixing uniformly; uniformly mixing the mixture with the lactose based on the amount of the formula according to a uniform progressive increasing method; and uniformly mixing the magnesium stearate based on the amount of the formula, and tabletting. The tablets have the advantages of stable quality, controllable related substances, good dispersibility and high dissolution speed.

The invention provides a method for preparing amorphous atorvastatin calcium. The amorphous atorvastatin calcium is prepared by undergoing a four-step reaction. The method comprises the following steps of: continually performing acidolysis deprotection and an alkali hydrolysis reaction in the same boiler under the condition that methanol and tetrahydrofuran are taken as solvents; particularly extracting a generated calcium salt with propyl acetate or butyl acetate or ethyl acetate; adding acetone for dissolving; concentrating a part; and directly drying under reduced pressure to obtain amorphous atorvastatin calcium, wherein the total yield is more than or equal to 75 percent. Due to the adoption of the method, the reaction period is greatly shortened, the preparing period can be shortened by more than 30 hours, the production cost is lowered, environmental pollution is reduced, the product quality is improved, the process operating steps are simplified, industrial production is easy, operation is convenient, the synthesis yield is high, the raw material cost is low, the product quality is good, and the obtained atorvastatin calcium is amorphous.

The invention relates to a preparation method of an atorvastatin calcium preparation. According to the method, atorvastatin calcium is mixed with a hydrophilic diluent and an alkali diluent in an equal increment way, and then mixed with a disintegrating agent and aerosil; an adhesive is added into the mixture; ethanol solution wet granulation is carried out; and then microcrystalline cellulose is added; and tabletting and film coating are carried out to obtain the preparation. The method can well solve the problem of influence of alkaline earth metal salt on bioavailability of atorvastatin calcium preparation, so as to realize good stability, bioavailability and dissolution rate of atorvastatin calcium preparation.

The invention discloses a synthesis method for a chiral intermediate of atorvastatin calcium, and belongs to the technical field of medical intermediate synthesis. The synthesis method is characterized in that according to the process route, not only are dangerous, highly toxic and expensive chemicals such as butyl lithium, editpotassium cyanide and periodic acid in chemical synthesis prevented from being used, but also an ee value of the chiral intermediate is effectively improved due to usage of a mixed chiral catalysts of titanium iso-propylate and S-xenol. According to the synthesis method, the raw materials are low in cost and easy to obtain, the route operation is easy, the repeatability is good, the yield is very high, and the synthesis method is suitable for industrial production.

The invention relates to a preparation method of a high-stability amlodipine atorvastatin calcium tablet. The preparation method of the high-stability amlodipine atorvastatin calcium tablet is characterized in that the amount of peroxide in microcrystalline cellulose is controlled. The preparation method of the high-stability amlodipine atorvastatin calcium tablet comprises the following steps: A, granulating of atorvastatin calcium, concretely comprising the steps of firstly dissolving a surfactant in water, adding a binding agent, stirring and dissolving, secondly mixing atorvastatin calcium, calcium carbonate, other diluents and a disintegrant, thirdly, granulating, and fourthly, drying wet granules obtained in the step three, so that dry atorvastatin calcium granules are prepared; and B, preparing of finished granules, concretely comprising the steps of firstly adding amlodipine besylate, a disintegrant and a flow aid into the dry atorvastatin calcium granules, secondly, uniformly mixing powder obtained in the step one in a mixing machine, thirdly, adding a lubricating agent, and uniformly mixing, and fourthly, pressing the powder into tablets.

The invention discloses a synthetic method of an atorvastatin calcium intermediate. The synthetic method comprises the following steps: preparing [(4R, 6S)-6- brooethyl-2,2-diemthyl-1,3-dioxane-4-group] tert-butyl acetate (5) by (3S)-4-bromine-3-hydroxyl ethyl butyrate through condensation, asymmetric biological catalytic reduction and hydroxyl protection; and preparing an atorvastatin calcium intermediate [(4R, 6S)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-group] tert-butyl acetate through catalytic hydrogenation reduction of raney nickel after 5 is condensed with nitromethane under action of cuprous bromide and a nitrogen-containing compound ligand. According to the synthetic method disclosed by the invention, steps are shortened, cost is lowered, and therefore, the synthetic method is more suitable for large-scale preparation.

The invention relates to a stable pharmaceutical formulation comprising an intimate admixture or admixture of crystalline or amorphous atorvastatin calcium, and a stabilizing-effective amount of a water-insoluble alkaline excipient or a combination of one or more water-insoluble alkaline excipients thereof, a stabilizing-effective amount of an antioxidant or a combination of one or more antioxidants thereof, and at least one or more additional pharmaceutically acceptable inert excipients or carriers, and a method for the preparation of the said formulation by wet and dry granulation. The invention further relates to a stabilized intimate admixture of atorvastatin calcium, a water-insoluble alkaline excipient and an antioxidant and a method for the preparation of the said intimate admixture by co-precipitation and co-milling.

The invention relates to a determining method of an atorvastatin calcium related substance. The method comprises the following steps of 1, preparing a test solution, i.e. taking a proper amount of atorvastatin calcium, adding a solvent to dissolve and quantitatively dilute the atorvastatin calcium until about 1mg of atorvastatin calcium is contained in 1ml of solution, and taking the solution as the test solution; 2, preparing a mixed reference substance solution, i.e. weighing a proper amount of reference substances of an impurity A, an impurity B, an impurity C, an impurity D and an impurity E, and a proper amount of reference substance of the atorvastatin calcium, adding the solvent to dissolve and quantitatively dilute the reference substances until about 3 micrograms of impurity A, 2 micrograms of impurity B, 2 micrograms of impurity C, 2 micrograms of impurity D, 2 micrograms of impurity E and 10 micrograms of atorvastatin calcium solution are contained in 1ml of solution, and taking the solution as the mixed reference substance solution; 3, performing HPLC (High Performance Liquid Chromatography) analysis, i.e. taking 20 microliters of test solution and 20 microliters of mixed reference substance soulution, respectively filling the test solution and the mixed reference substance into a liquid chromatograph, recording a chromatogram until a gradient elution program is finished, and according to the peak area of the chromatogram, calculating the content of each component.

The present invention is a new stable drug composition particularly suitable for use as an antihypercholesterolaemic or antihyperlipidaemic agent. The present invention is specifically a drug composition comprising a pharmaceutical, a complexing agent and a surfactant, and a method for manufacturing same. When applied to unstable drugs with low solubility and poor bioavailability, like HMG-CoA reductase inhibitors and especially atorvastatin calcium amorphous form, the resulting drug composition is more stable and is characterized by an improved dissolution profile.

A detection method of atorvastatin calcium capsule related substances of the invention relates to a method which tests or analyzes a drug by separating the drug into various components by adsorption, and the method can detect a single component of related substances in an atorvastatin calcium capsule, and facilitates the improvement of quality standard of atorvastatin calcium capsules. According to the invention, a sample solution to be tested, a self-control solution, and a blank solution are weighed; the solutions are injected into a liquid chromatography, wherein the chromatographic conditions are as follows: a chromatographic column with octadecyl silane bonded silica as a filler is selected; acetonitrile-tetrahydrofuran is used as a mobile phase A; 0.56% ammonium biphosphate solution-mobile phase A is used as a mobile phase B; 0.56% ammonium biphosphate solution- mobile phase A-methanol is used as a mobile phase C; gradient elution is performed; the detection wavelength is 240-250 nm, and the column temperature is 20 DEG C-30 DEG C, wherein in the 0.56% ammonium biphosphate solution, 0.56% is a mass-volume ratio; and a chromatogram is recorded.

The invention provides a quickly-dissolved atorvastatin calcium tablet and a preparation method thereof. The atorvastatin calcium tablet provided by the invention does not contain surface active agents and alkaline materials, is simple in process, and can be quickly dissolved in the stomach, thereby enhancing the compliance and treatment effect of the administration of patients.

The invention relates to a tablet composition containing ezetimibe and atorvastatin calcium and a preparation method of the composition. According to the method, the stability of atorvastatin calcium in a pharmaceutical composition can be effectively improved, and the in-vivo bioavailability of the medicine is improved. Moreover, the method has the advantages that the process is simple and feasible to operate, the requirement on preparation equipment is low, and the production cost is reduced. The solid oral preparation is used for treating or preventing cardiovascular and cerebrovascular diseases.

The invention relates to a method for preparing high-purity (4R, 6R)-6-{2-[5-isopropyl-3-phenyl-2(4-fluorophenyl)-4-(phenylcarbamoyl)-yrrol-1-yl]- ethyl}-2, 2-dimethyl-[1, 3]-dioxane-4-yl-tert-butyl acetate, which comprises the following steps: step one, [5-methyl-4-isopropyl-2-phenyl-1(4-fluorophenyl)-3-(phenylcarbamoy1)-1,4-hexanedione](II) and [(4R,6R)-2,2-dimethyl-6-(2-aminoethyl)-[1,3]-dioxane-4-yl-tert-butyl acetate](III) with a mol ratio of between 0.71 and 1.12 to 1 are weighed, an acid catalyst which is 1.05 to 1.15 times of mol number of the formula (II) is weighed, the mixture is dissolved in a non-hydroxy solvent which is 3.0 to 4.2 times of the weight of the formula (II) under the protection of nitrogen and the stirring, and heating reflux and azeotropic water entrainment are performed until an HPLC shows that the reaction is finished; and second two, the solvent is removed under vacuum, then a water-isopropanol mixed solvent with a volume ratio of 2 to 5 is used to recrystallize the mixture, and a key intermediate of synthetic atorvastatin calcium which has an HPLC purity not less than 99.0 percent and is expressed by the formula (I) is obtained after the pump filtration and drying. The method has the advantages of simple process, low equipment requirement, low cost, convenient and quick recovery of the solvent, less environmental pollution, and high product purity.

The invention provides a preparation process of atorvastatin calcium, which is characterized by being divided into two steps when preparing a condensation compound (4R-cis)-1,1-dimethyl ethyl-6-[2-[2-(4-fluorophenyl)-5-(1-methyl ethyl)-3-phenyl-4-[(phenyl amino)-carbonyl]-1H-pyrrole-1-yl]ethyl]-2,2-dimethyl-1,3-dioxane-4-acetate: 1), adding (4R-cis)-6-aminoethyl-2,2-dimethyl-1,3-dioxane-4-tertbutyl acetate (called ATS-9 for short) into a mixed solvent of n-heptane, tetrahydrofuran and toluene to react with pivalic acid; and 2), adding 4-fluorine-alpha-[2-methyl-1-oxygen-propyl]-gamma-oxo-N,beta-diphenyl phenyl butyramide (called M-4 for short) and rising the temperature for reaction. The invention has the advantage of capability of greatly improving the yield of the intermediate condensation compound and is more in favor of industrialized production.

The invention relates to an atorvastatin calcium dried suspension and a preparation method thereof. The atorvastatin calcium dried suspension comprises the following components in portion by weight: 1to 10 portions of atorvastatin calcium, 10 to 95 portions of filling agent, 1 to 30 portions of suspension and/or suspending agent, 2 to 40 portions of flavoring agent, and 0.2 to 2.0 portions of lubricating agent. The atorvastatin calcium dried suspension has the advantages of high dispersity, even distribution, quick absorption, high bioavailability, good adaptability, good mouthfeel, stabilityand the like. The atorvastatin calcium dried suspension can be applied to regulation of blood fat.

The invention discloses an ezetimibe and atorvastatin calcium tablet and a preparation method thereof. The tablet is prepared from ezetimibe particles and atorvastatin calcium particles through double-layer tabletting, wherein the ezetimibe particles comprise the following components: ezetimibe, a binder, a surfactant, a water-soluble filling agent, a water-insoluble filling agent, a disintegrating agent and a lubricant; during pelletizing of the ezetimibe particles, the ezetimibe and the surfactant are dissolved or dispersed into a binder solution; the water-soluble filling agent is added to uniformly mix; and other auxiliary materials are added for pelletizing. During the preparation of the ezetimibe layer, the auxiliary materials are added in specific sequence, so that the in-vitro release problem of the ezetimibe is effectively solved.