30 results about "Pimobendan" patented technology

The invention relates to novel solid formulations comprising as pharmaceutically active compound pimobendan and to processes for producing such solid formulations. The invention furthermore relates to a method for manufacturing a medicament for the prevention and/or treatment of congestive heart failure, wherein the solid formulations according to the invention are used.

The present invention is directed to a composition comprising particles of pimobendan with an integral coating of a carrier matrix which serve to ensure a rapid dissolution of the active substance at each pH condition representing the gastrointestinal tract and therefore a reliable absorption, and a method of pimobendan microencapsulation using the spray congealing technology and incorporating the coated particles into oral formulations, for example into tablets.

The present invention is directed to a preserved liquid aqueous pharmaceutical composition comprising one or more etherified cyclodextrin derivatives; one or more water-soluble preservatives; preferably selected from the group consisting of sorbic acid or salts thereof, preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or salts thereof, preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabenes and salts thereof, preferably methylparabene, ethylparabene, propylparabene, butylparabene, butylparabene sodium; or combinations thereof; and at least one pharmaceutically active compound which is poorly water-soluble, very poorly water-soluble or water-insoluble. The liquid aqueous pharmaceutical composition provides an acceptable solubility of the pharmaceutically active compound, such as pimobendan, in aqueous solution whereby the water-soluble preservatives retain their effectiveness in the presence of the etherified cyclodextrin derivatives allowing the use in an oral administration form.

The invention relates to pimobendan for use in a method of reducing the heart size and/or delaying the onset of clinical symptoms in a patient suffering from asymptomatic (occult, preclinical) heart failure, preferably congestive heart failure, due to mitral valve disease (MVD), and/or delaying the onset of heart failure, preferably congestive heart failure, in a patient suffering from asymptomatic (occult, preclinical) heart failure, preferably congestive heart failure, due to mitral valve disease (MVD), wherein the patient is preferably a mammal, more preferably a human, a dog, a cat or a horse, and most preferably a dog.

The invention discloses a chemical synthesis method of Pimobendan. The method comprises steps as follows: acetanilide and 2-methyl-3-(chloroformyl)propionate react to produce 3-p-acetylaminobenzoyl methyl butyrate in a mixed organic solvent under the action of a composite catalyst, 3-p-acetylaminobenzoyl methyl butyrate reacts with a nitration reagent, 3-(4-acetamido-3-nitrobenzoyl)-methyl butyrate is produced and subjected to a reflux reaction with alkali in an alcohol solvent to produce 3-(4-amino-3-nitrobenzoyl) butyrate, 3-(4-amino-3-nitrobenzoyl) butyrate and hydrazine hydrate are subjected to a reflux reaction, 4,5-dihydro-5-methyl-6-(4-amino-3-nitrophenyl)-3(2H)-pyridazinone is produced and reduced with zinc powder in absolute methanol, 4,5-dihydro-5-methyl-6-(3,4-diaminophenyl)-3(2H)-pyridazinone is produced and subjected to a reflux reaction with p-anisaldehyde, and Pimobendan is obtained. The method comprises a few reaction steps, operation is safe and convenient, and the cost is low.

The invention discloses pimobendan sustained-release tablets for a pet and a preparation method thereof. The pimobendan sustained-release tablets disclosed by the invention are stable and safe to use and consist of a solid dispersion of pimobendan, a sustained-release material, a filling agent, an adhesive, a lubricant and a flavoring agent. The pimobendan sustained-release tablets disclosed by the invention have the characteristics of convenience in administration, lasting action and stable curative effect.

The invention discloses a preparation method of a key intermediate of Pimobendan. The method comprises steps as follows: (i) a compound I is synthesized; (ii) the compound I is subjected to nucleophilic substitution, and a compound II is produced; (iii) the compound II is subjected to a nitration reaction, and a compound III is produced; (iv) the compound III is subjected to a hydrolysis reaction, and a compound IV is produced; (v) the compound IV is subjected to a decarboxylation reaction, and a compound V is produced; (vi) the compound V and a hydrazine hydrate solution react, and a compound VI is produced; (vii) the compound VI and a hydrazine hydrate solution react, and a compound VII is produced. The invention provides the preparation method of the key intermediate of Pimobendan, namely, 4,5-dihydro-5-methyl-6-(3,4-diaminophenyl)-3(2H)pyridazinone. A few reaction steps are used, highly toxic and high-corrosivity raw materials such as liquid bromine, potassium cyanide and the like are not required to be used, and the method has low environmental pollution and facilitates industrial amplification.

The invention relates to a novel preparation process of pimobendan. The process comprises short steps, does not refer to dangerous and highly toxic reagents such as Br2, KCN and NaH which have limitation in wide industrial use, is simple in operation and mild in reaction conditions and has obvious superiorities in industrial production.

The present invention relates to the preparation method and application of chiral pimobendan, comprising the following steps: preparing chiral intermediate 1 with chiral reagent, diammonium phthalate and aluminum trichloride; using chiral intermediate 1, Prepare intermediate 2 with base, N,N-dimethylformamide and malonic acid substituted ester; prepare intermediate 3 with intermediate 2 and a catalytic hydrogenation catalyst; prepare intermediate 4 with intermediate 3, alcohol and hydrazine hydrate; Intermediate 4, N,N-dimethylformamide and 4-methoxybenzaldehyde are prepared to obtain chiral pimobendan, and the method of the present invention only needs 5 steps to obtain chiral pimobendan, and the current The steps are shortened by more than half, and the starting materials are simple and easy to obtain; and the chiral pimobendan can be used to treat mild, moderate or severe congestive heart failure in dogs caused by atrioventricular valve insufficiency or myocardial hypertrophy , hypertrophic cardiomyopathy in pets, etc.

The present invention relates to the preparation method of pimobendan, comprising the following steps: prepare the first intermediate with 2-chloropropionyl chloride, diammonium phthalate and aluminum trichloride; prepare the first intermediate with the first intermediate, alkali, N,N ‑Dimethylformamide and malonic acid substituted ester prepare the second intermediate; prepare the third intermediate with the second intermediate and a catalytic hydrogenation catalyst; prepare the fourth intermediate with the third intermediate, alcohol and hydrazine hydrate; The fourth intermediate, N,N-dimethylformamide and 4-methoxybenzaldehyde are prepared to obtain pimobendan, and the method of the present invention only needs 5 steps to obtain pimobendan, shortening the current steps more than half, and the starting materials are simple and easy to obtain.

The invention relates to a preparation technology of a pimobendan key intermediate 6-(4-amino-3-nitro phenyl)-5-methyl-4, 5-dihydrogen pyridazine-3(2H)-ketone (formula V). The preparation technology is short in synthesis route and simple in operation, thus having large industrial production prospect. The chemical reaction formula is shown in the description.

The invention discloses an impurity detection method for a pimobendan soft chewing dosage form, which is characterized in that three-phase high performance liquid chromatography is used for determination, and the chromatographic conditions comprise that a chromatographic column is C18, 4.6 mm * 250 mm, 4 [mu] m; a mobile phase A is a 2.6 g/L sodium dihydrogen phosphate solution, and the pH is adjusted to 3.0 by phosphoric acid; a mobile phase B is acetonitrile-methanol in a ratio of 80: 20; the column temperature is 45 DEG C; the detection wavelength is 290 nm; and the flow velocity is 1.0 ml/min. The pimobendan soft chewing dosage form solution is measured under the liquid chromatogram condition, and the impurity condition is judged according to the main peak and the impurity peak. In addition, under the method, a preservative in the pimobendan soft chewing dosage form can be detected. By adjusting the mobile phase system and optimizing the mobile phase gradient, the main peak of pimobendan appears at the gradient change mitigation position, the auxiliary material is completely separated from the main peak and the impurity peak, the auxiliary material does not interfere with impurity detection, the specificity is high, the sensitivity is high, and the impurity response is high.

The invention discloses a novel method for preparing pimobendan from a by-product for synthesizing the pimobendan. The method comprises the following steps that the by-product (the chemical name is (5RS)-6-[1-(4-methoxybenzyl)-2-(4-methoxyphenyl)-1H-benzimidazole-6-yl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone) obtained in the pimobendan synthesizing process is dissolved into a mixed solvent and reacts with ceric ammonium nitrate (CAN) at 20-25 DEG C for 2-3 hours so as to obtain a pimobendan crude product; and the obtained pimobendan crude product is heated and refluxed in an organic solvent, and cooling, filtering and drying are carried out so as to obtain the pimobendan. According to the method, the unwanted by-product is converted into a required pimobendan product, waste is turned intowealth, and therefore the production cost is greatly lowered.

The invention provides the application of a phosphodiesterase inhibitor or a pharmaceutical composition of the phosphodiesterase inhibitor in preparation of medicines for treating novel coronavirus pneumonia, screening of systematic biology and cellular level experiments verify that zardaverine, Pimobendan and crisaborole can inhibit proliferation of novel coronavirus to different degrees on the cellular level; wherein zardaverine has the strongest anti-new coronavirus effect, Pimobendan has the second anti-new coronavirus effect, and zardaverine, Pimobendan and crisaborole can be used for preparing medicines for treating novel coronavirus pneumonia.

The invention relates to preparation of a 6-(3,4-diamino phenyl)-5-methyl-4,5-dihydropyridazine-3(2H)-ketone key intermediate for synthesizing 2-(4-methoxyphenyl)-5(6)-(5-methyl-3-oxo-4,5-dihydro-2H-6-pyridazinyl)benzimidazole. The technology is short in synthetic route and easy to operate and has an industrialized enlarged production prospect.

The invention relates to the technical field of pharmaceutical compositions, in particular to a compound pharmaceutical composition containing benazepril and pimobendan for pets and a preparation method of the compound pharmaceutical composition. The pharmaceutical composition comprises the following active pharmaceutical ingredients in percentage by weight: 1%-8.0% of benazepril hydrochloride, 0.5%-4.0% of pimobendan, 42%-71% of diluent, 1%-5% of sustained-release skeleton, 10%-20% of coating taste masking material, 1.5%-4% of disintegrating agent, 1%-5% of adhesive, 5%-15% of solubilizer, 1%-5% of flow aid, 1%-3% of lubricant , 0.5%-2% of corrigent and a small amount of pigment. The compound composition prepared by the invention has the characteristics of convenience in administration, lasting effect and stable curative effect, can relax blood vessels and reduce blood pressure so as to reduce heart burden, and also can improve myocardial contractility and improve the survival rate of sick dogs; the medicine is high in effect taking speed and high in bioavailability; moreover, a taste masking coating process and a proper amount of meat flavor flavoring agent are added, so that it has a pleasant taste for pets and the medicine taking compliance of animals is greatly improved.

The invention relates to a novel preparation process of pimobendan. Specifically, a Suzuki coupling reaction is carried out on a compound shown as a formula I (6-(2-bromo-1H-benzo[d]imidazol-6-yl)-5-methyl-4, 5-dihydropyridazin-3(2H)-one) and a compound shown as a formula II (p-methoxyphenylboronic acid or p-methoxyphenylboronic acid pinacol ester) under the action of a Pd catalyst, so that the preparation of the pimobendan is realized.