120 results about "Pitavastatin calcium" patented technology

The present invention relates to novel anhydrous amorphous forms of bis[(E)[4-(4-fluorophenyl)isopropyl[methyl(methylsulfonyl)amino]pyrimidinyl](3R,5S)-3,5-dihydroxyhept enoic acid]calcium salt (rosuvastatin calcium), (±)7-(3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl)3,5-dihydroxy heptenoic acid monosodium salt (fluvastatin sodium) and bis[(E)-3,5-dihydroxy-7-[4′-(4″-fluorophenyl)-2′-cyclopropyl-quinolin-3′-hept-6-enoic acid]calcium salt (pitavastatin calcium), to processes for their preparation, to pharmaceutical compositions containing them and to methods of treatment using the same. The rosuvastatin calcium, pitavastatin calcium and fluvastatin sodium obtained are known valuable agents useful in treating hyperlipidemia and hypercholestrolemia.

The invention discloses a drug composition and making method of stable calcium Bimvastatin, which comprises the following parts: 0.01-10% calcium Bimvastatin, 10- 93% filler, 1-30% disintegration agent, 0.01-5% lubricant and 0.1-80% alkali findings.

The invention relates to a medicinal composition, in particular to a pitavastatin calcium composition stabilized by using an alkaline reagent and a preparation method thereof. The pitavastatin calcium composition is characterized in that: the alkaline reagent is magnesium oxide, the pH of the aqueous solution or the suspension of the magnesium oxide is more than 9 and less than 12, and the alkaline reagent can remarkably improve the stability of the pitavastatin calcium composition. The pitavastatin calcium composition is suitable for long-term storage and has good clinical effect. The preparation method for the pitavastatin calcium composition is simple, convenient to operate and suitable for industrialized production.

Provided is a method for treating hyperlipidemia or hypercholesterolemia, which comprises administering effective doses of ezetimibe and pitavastatin or a salt or lactone derivative thereof.

The invention discloses a segregation detection method of drapery tartan calcium and optical isomer (impurity), which is characterized by the following: adapting high effective gas-chromatography or high effective gas-chromatography mass spectrography to detect the optical isomer of drapery tartan calcium; segregating the drapery tartan calcium and optical isomer of drapery tartan calcium.

The invention provides a pitavastatin calcium enteric sustained-release micropill preparation and a preparation method thereof, which can solve the problems that: (1) pitavastatin calcium is easily subjected to inversion of configuration under the condition that gastric juice has a low pH value, and has low stability, and (2) common tablets are released too quickly, so that active ingredients cannot fully achieve the effect of reducing cholesterol in the prior art. The technical scheme is that: the pitavastatin calcium enteric sustained-release micropill preparation comprises a medicine-containing pill core, an isolation layer, a sustained-release layer and an enteric layer from inside to outside, wherein the medicine-containing pill core comprises pitavastatin calcium and pharmaceutical excipients. The invention also provides a preparation method for the micropill preparation. The prepared micropill is not released in the gastric juice, and medicines are prevented from being exposed in the acid environment; by adopting microporous film coating technology, the medicines can be slowly released from the pill core, the blood concentration is kept balanced, the medicine taking frequency is reduced and the compliance of the patient is improved.

Processes for preparing pravastatin, intermediates and pharmaceutically acceptable salts thereof are provided Crystalline forms of pravastatin, intermediates and pharmaceutically acceptable salts thereof are also disclosed.

The invention relates to a preparation method of pitavastatin calcium for treating hyperlipidemia. The preparation method comprises the following steps: performing cyclization on 2-amino-4'-fluorobenzophenone (III) and ethyl 3-cyclopropyl-3-oxo-propanoate (II), and then reducing with LiAlH4 to obtain 2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline methanol (V); bromizing the V to obtain 2-cyclopropyl-3-bromomethyl-4-(4-fluorophenyl) quinoline (VI); reacting the VI with triphenylphosphine to obtain (2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-yl) methyltriphenylphosphonium bromide (VII), performing alkali treatment on a phosphonium salt, then forming phosphonium ylide, performing condensation with (3R, 5S)-6-oxo-3, 5-isopropylidene-dioxo-6-heptenoic acid tert-butyl ester (VIII) to obtain a compound IX; and acidifying the compound IX with hydrochloric acid, performing hydrolysis deprotection with sodium hydroxide, performing salt formation and purification with chiral amine and forming a calcium slat to obtain a final product. The whole route has reasonable design, the process flow is simple, starting raw materials and reagents used by the preparation method can be purchased from the market, the reagents with severe toxicity and serious pollution are not used in a reaction process, the post-treatment of an intermediate is simple, and the preparation method has the advantages of high yield and is easy to purify.

The invention relates to a preparation method of a cholesterol reduction drug, particularly relates to a preparation method of pitavastatin calcium as a crude drug of the cholesterol reduction drug, and aims at the problems that the pitavastatin calcium synthetic technology in the prior art is long in steps and complicated in operation, and uses strongly corrosive reagents which is environmentally unfriendly, causes serious corrosion to equipment, and may not facilitate industrial production. The invention provides the new preparation method of the pitavastatin calcium, the new preparation method is as follows: 3-bromomethyl-2-cyclopropyl-4-(4-fluorophenyl)quinoline is prepared from 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehyde by a one step reaction, and then reacts with an organophosphorus reagent to obtain pitavastatin calcium intermediate phosphorus ylide, on the basis of improving of the yield to 80%, the reaction steps are reduced, and the reaction difficulty is reduced, and hydroxylamine hydrochloride is selected as a deprotection reagent, so that the new preparation method is mild in reaction conditions, environmentally friendly, high in yield, and beneficial to industrial production.

The invention discloses a tablet composition containing pitavastatin calcium and a preparation method of the tablet composition. The tablet composition contains main medicine-pitavastatin calcium, porous filler, a disintegrating agent, a lubricating agent and opadry film premix. A direct powder compression method is adopted; the stability of a product is remarkably improved.

The invention relates to a preparation method of a pitavastatin calcium intermediate compound which has a chemical name of 2-cyclopropyl-3-hydroxymethyl-4-(4-fluorophenyl)-quinoline and is shown in Formula (I). The pitavastatin calcium intermediate compound is prepared by hydrolyzing and reducing an ester compound shown in Formula (II) under specific conditions.

The invention relates to the technical field of medicine, particularly a preparation method of pitavastatin calcium by recrystallization. The method is implemented in a way that: pitavastatin calcium is dissolved in a tetrahydrofuran/water mixed solvent, wherein the solubility is high; and after gradually removing the tetrahydrofuran by volatilization, since the solubility of the pitavastatin calcium in water is very low, the pitavastatin calcium gradually crystallizes and precipitates, thereby obtaining the pitavastatin calcium solid with favorable crystal form and also refining and purifying the pitavastatin calcium.

The invention discloses a method for preparing pitavastatin calcium. The method comprises the following step: performing seven-step synthesis on 3-cyclopropyl-oxopropionate (comprising methyl ester and ethyl ester), (2-aminophenyl)(4-fluorophenyl) ketone and (4R-cis)-6-[(acetoxy)methyl]2,2-dimethyl-1,3-dioxane-4-tert-butyl acetate which are used as initial raw materials so as to obtain the product. The reaction in each step is a conventional reaction and is suitable for large-scale production. The process is stable, the reaction conditions are mild, the after-treatment operation is simple, the intermediate is easy to separate, and the technical bottleneck in the existing pitavastatin calcium synthesis is solved.

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 discloses a stable pitavastatin calcium pharmaceutical composition, at least one of zinc oxide, aluminium oxide and ferric oxide is taken as a stabilizing agent, and the obtained pitavastatin calcium pharmaceutical composition and a further-prepared preparation product both have good stability, and the dissolving-out property of the preparation accords with the medicinal standard.

The invention discloses a preparation method of pitavastatin calcium. The preparation method comprises the following steps: (1) preparing an intermediate I; (2) preparing an intermediate II; (3) preparing an intermediate III; (4) preparing an intermediate IV; and (5) preparing pitavastatin calcium. The preparation method disclosed by the invention has the beneficial effects that the synthetic route disclosed by the invention is simple and feasible and reasonable in cost and suitable for mass production.

The invention provides a pitavastatin calcium preparation, which employs a direct powder tabletting technology. The weight ratio of a medicine to the auxiliary materials is 1:90-150, the pharmaceutic auxiliary materials comprise the following components by weight: 20-35% of filler, 20-40% of disintegrating agent, 20-30% of adhesive, 0.3-20% of lubricant and 2-5% of coating powder. The auxiliary materials are common pharmaceutic auxiliary materials, the medicine stability is good, the biological availability is high, the powder fluidity is good in tabletting, the compressibility is strong, and the requirements of coating and production can be satisfied.

The invention relates to the technical field of medicine, particularly a preparation method of a pitavastatin calcium intermediate, which comprises the following steps: in the process of synthesizing the pitavastatin calcium intermediate (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl)-5-hydroxy-3-oxo-6-ethylheptenoate, reacting ethyl acetoacetate with s-sulfinyl amine to generate chiral imine, reacting with butyl lithium to generate chiral imido-enolate, and carrying out condensation reaction with (E)-3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl-2-acraldehyde to obtain the intermediate s-(E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-5-hydroxy-3-oxo-6-ethylheptenoate with optical activity. The ee value is higher than 95%, the subsequent preparation of pitavastatin calcium does not need to remove inactive components by resolution, and the yield relative to the raw material is higher.

The invention relates to the preparation field of compounds and particularly relates to a novel crystal form of (-)-(3R,5S)-7-[2- cyclopropyl-4-(4- fluorobenzene group) quinoline-2-group]-3,5- dyhydroxyl-6(E)- heptylate and a preparation method of the novel form. By virtue of solvent crystallization, the method can obtain the crystal form of the (-)-(3R,5S)-7-[2- cyclopropyl-4-(4- fluorobenzene group) quinoline-2-group]-3,5- dyhydroxyl-6(E)- heptylate with enantiotopic impurity less than 0.50% and diastereomeric impurity less than 0.30%.