66 results about "Pitavastatine" patented technology

The invention relates to the field of medicinal preparations, and in particular relates to a novel pitavastatin calcium oral disintegrating tablet composition and a preparation method thereof. The composition is mainly formed by combining soluble auxiliary materials and insoluble auxiliary materials in a certain proportion. The pitavastatin calcium composition has the characteristic of being rapidly disintegrated in the oral cavity to release medicines so as to promote effects of absorption and utilization.

The invention discloses a synthesis method of pitavastatin tert-butyl ester, which comprises the following steps: carrying out a reaction on (4R-Cis)-6-chloromethyl-2,2-dimethyl-1,3-dioxolane-4-tert-butyl acetate with a substance A under the action of a first base catalyst to obtain a substance B; oxidizing the substance B with an oxidizing agent to obtain a substance C; carrying out a reaction with 2-Cyclopropyl-4-(4-fluorophenyl)-quinoline-3-formaldehyde under the action of a second base catalyst to obtain a substance D; and finally, performing acid deprotection to obtain the pitavastatin tert-butyl ester. The method has the advantages of mild and controllable reaction conditions, wherein the reaction conditions of Julia olefination are free of requirement of ultralow-temperature reaction, so that the synthesis method has advantages of convenience and simplicity in operation, good stereoselectivity and high yield, and the synthesized pitavastatin tert-butyl ester is completely free of cis-isomer and high in purity.

The invention relates to the field of medicine quality detection, in particular to a method for detecting potential mutagenic impurities in pitavastatin calcium tablets. The method comprises the following steps: dissolving a to-be-detected sample by adopting a solvent, and detecting by adopting a high performance liquid chromatography under the chromatographic conditions that a mobile phase comprises an organic acid salt buffer solution and acetonitrile; the flow rate is 1.0 mL / min; the column temperature is 25-40 DEG C; a chromatographic column: octadecylsilane chemically bonded silica is used as a filler; the sample injection volume is 50 [mu] L; the detection wavelength ranges from 270 nm to 280 nm; an elution mode is gradient elution; the potential mutagenic impurities are an impurity1 and an impurity 2. According to the method disclosed by the invention, the pitavastatin calcium, the impurity 1 and the impurity 2 can be effectively separated; meanwhile, interference of other related impurities of pitavastatin calcium on detection of the impurity 1 and the impurity 2 is avoided, the content of potential mutagenic impurities 1 and 2 of the pitavastatin calcium tablets can be accurately detected, the quality of the pitavastatin calcium tablets is effectively monitored, and the medication safety is improved.

The invention relates to a method for preparing high-optical purity pitavastatin calcium. The method comprises the following steps of: deprotecting (3R,5S)-dyhydroxyl-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dyhydroxyl-3,5-Oisopropylidene-6-tert-butyl heptenoate (I) serving as an initial raw material by using acid, and removing impurities under a certain pH value; adding excessive D-(+)benzyl methylamine, and crystallizing to extract heptenoic acid amine salt (IV); and adding calcium chloride to obtain the pitavastatin calcium. The method has the advantages that the reaction condition is mild, the purity of the product is high, the optical purity is more than or equal to 99.5 percent, the yield is more than or equal to 50 percent, the problems of high difficulty of separation and purification and low yield in the conventional method for synthesizing the pitavastatin calcium, and the method is suitable for industrialization.

The invention discloses a pitavastatin calcium lipid solid preparation and a preparation method thereof. The preparation method comprises the following steps: preparing pitavastatin calcium lipid with excellent quality from pitavastatin calcium, DPPC (dipalmitoyl phosphatidylcholine), stearamide, octadecylamine and Tween 80 in a specific weight proportion; and preparing the pitavastatin calcium lipid into a solid preparation by a conventional preparation method. Compared with the existing preparation, the preparation disclosed by the invention has the advantages of greatly improved stability and bioavailability, enhanced quality, reduced toxic and side effects, smooth and stable drug release, and remarkable curative effect.

The present invention provides a therapeutic agent for hyperlipidemia having an excellent effect of lowering the cholesterol and triglyceride level in blood plasma.The present invention relates to a prophylactic and / or therapeutic agent for hyperlipidemia, a prophylactic and / or therapeutic agent for obesity or diabetes mellitus, and a prophylactic and / or therapeutic agent for metabolic syndrome, each agent including a compound represented by the formula (1), or a salt thereof, and a statin, particularly pitavastatin, in combination.

The invention relates to a preparation method of a pitavastatin calcium intermediate, which comprises the following steps: (1) under the protection of nitrogen, carrying out chemical reaction on compounds N7 and NBS and a solvent at 30-80 DEG C to prepare an intermediate product compound N8.1, and (2) adding triphenylphosphine into the reaction solution obtained in the step (1), heating to 60-120DEG C for reaction, cooling to 0-20 DEG C for stirring crystallization after the reaction is finished, and filtering to obtain a compound N8.2, wherein the specific synthetic route is as follows. Thepreparation method has the advantages of mild reaction conditions, no generation of a large amount of bromine-containing and phosphorus-containing wastewater in the reaction process, no influences ofacids and bases on the intermediate product compound N8.1, and difficult decomposition, so the yield of the target product is high and reaches 90% or above, the purity is high and reaches 99% or above, and the product has the advantages of simple post-treatment, greenness and environmental protection, and suitableness for industrial production.

The invention relates to a pharmaceutical composition containing rosuvastatin or pitavastatin compounds and B vitamins; wherein the content of rosuvastatin or pitavastatin compounds is 1-40 mg, and the content of B vitamins is 0.1-50 mg . The invention also provides the application of the pharmaceutical composition in the preparation of medicines for preventing, treating and delaying atherosclerosis and related cardiovascular and cerebrovascular diseases. The invention has the advantages that the curative effect of the statin lipid-lowering drugs can be improved, the vascular endothelial protection and anti-atherosclerosis aspects are superior to the statin lipid-lowering drugs, the side effects of the statin lipid-lowering drugs are reduced, and the toxicity is not increased, In addition, it can make it convenient for patients to take medicines and reduce medical expenses.

Production of pitavastatin calcium safely on an industrial scale with a high yield and high selectivity at low cost. A method of producing pitavastatin calcium including step (i) for acetalizing a compound represented by the formula (1) to give a compound represented by the formula (3), step (ii) for reacting a compound represented by the formula (3) with an acid to give a compound represented by the formula (4), and step (iii) for hydrolyzing a compound represented by the formula (4) and reacting same with a calcium compound.

The present invention relates to a kind of preparation method of pitavastatin calcium intermediate [[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl] methyl] triphenylphosphine bromide, comprising the following Said steps: make 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol and triphenylphosphine hydrobromide react in an organic solvent to obtain the target compound. The preparation method of the invention has easy-to-obtain raw materials, simple operation and high yield, effectively reduces phosphorus-containing waste water and phosphorus-containing waste residue, reduces production costs, and is beneficial to large-scale production.

The present invention provides a pharmaceutical product which includes a solid preparation comprising pitavastatin or a salt thereof, in which production of a lactone form thereof is suppressed.The pharmaceutical product is characterized by including a solid preparation comprising the following ingredients (A) and (B): (A) pitavastatin or a salt thereof; and (B) at least one member selected from the group consisting of carmellose and a salt thereof, crospovidone, and microcrystalline cellulose, and the solid preparation having a water content of 2.9 mass % or less, wherein the solid preparation is stored in a tight package.

The invention discloses a refining method of pitavastatin tert-butyl ester, which comprises the following steps: cooling and crystallizing a mixed solvent in which pitavastatin tert-butyl ester raw materials are dissolved, filtering, and drying; wherein, the mixed solvent It is a mixture of methyl tert-butyl ether and non-polar organic solvent; the non-polar organic solvent is n-hexane, n-heptane, cyclohexane, n-pentane, cyclopentane, octane or isooctane. According to the refining method of the present invention, the isomer content in the obtained pitavastatin tert-butyl ester is low, and the refining effect is good. Epimer impurity 1, epimer impurity 2 and enantiomer impurity The contents are all below 0.05%. Moreover, the refining method of the present invention has high yield, low uncontrollability, simple operation, is suitable for large-scale industrial production, and can prepare high-purity pitavastatin calcium.

A solid oral pharmaceutical composition is disclosed, which comprises: a first active ingredient, which is pitavastatin or a pharmaceutically acceptable salt thereof; a second active ingredient, which is ezetimibe or a pharmaceutically acceptable salt thereof; and at least one excipient, including a diluent, a stabilizing agent, a disintegrant, a binding agent, a sweetener, a lubricant, a glidant, a flavor, a coloring agent or a combination thereof.

The invention discloses miazine compounds as shown in a formula A which is disclosed in the specification and reaction intermediate compounds as shown in formulas B, C and D, wherein X is O or S, R is H,F,C1-C3 alkyl or C1-C3 alkoxy. The invention also discloses preparation methods of the intermediates and miazine compounds and an application of the miazine compounds in preparing medicaments for inhibiting HMG-CoA reductase and / or treating hyperlipidemia diseases. Compared with the pitavastatin, osuvastatin and atorvastatin in the prior art, the 6-isopropyl-2-(N-methyl-N-sulfonyl) amino-4-substituted phenoxy (or thiphenyl) miazine compounds have better or at least comparative activity for inhibiting the HMG-CoA reductase, and can be used for treating the hyperlipidemia diseases.

The invention relates to a pitavastatin calcium tablet pharmaceutical composition and a dry or wet preparation method thereof. Specifically, one aspect of the invention relates to a pitavastatin calcium tablet which comprises a tablet core and a coating layer, wherein the tablet core comprises 1 part of pitavastatin calcium, 40-120 parts of a filling agent, 4-20 parts of a disintegrating agent, 0.5-5 parts of an adhesive, 0.5-5 parts of a stabilizer and 0.3-3 parts of a lubricating agent. The tablet core can be made from lactose, microcrystalline cellulose, tricalcium phosphate, low substituted hydroxypropy cellulose, crospovidone, sodium carboxymethyl starch, aluminum-magnesium silicate, aluminum-magnesium metasilicate, hydroxypropyl methylcellulose, magnesium stearate and other excipients and combinations thereof. The tablet core can be prepared through a dry granulation tabletting process or a wet granulation tabletting process. The invention further relates to a preparation method of pitavastatin calcium tablets and application thereof in preparation of drugs for treating and / or preventing hypercholesteremia or familial hypercholesterolemia. The tablet pharmaceutical composition disclosed by the invention has excellent properties shown in the specification.