37 results about "Lercanidipine Hydrochloride" patented technology

The invention is a lercandipine hydrochloride crystal (form (HX) crystal) and the preparation method. The crystal has no crystalline water and virgule or crystalline solvent, and is a novel high-purity stable crystalline form, which is more suitable for the large-scale industrial production. The invention is characterized in the simple and easy operation; thus the invention is conducive to the preparation of the drug combination and the clinical use. The crystal uses the Cu-K alpha radiation; the X-ray powder diffraction spectra show expressed in the 2-theta angle has the following characteristics (see the above formula).

Disclosed herein is an improved, commercially viable and industrially advantageous process for the preparation of substantially pure Lercanidipine intermediate, 1,1,N- trimethyl-N-(3,3-diphenylpropyl)-2-aminoethyl acetoacetate. The intermediate is useful for preparing Lercanidipine, or a pharmaceutically acceptable salt thereof, in high yield and purity. The present invention further provides a novel crystalline form of Lercanidipine hydrochloride and a process for its preparation. The present invention also provides a process for the preparation of amorphous form of Lercanidipine hydrochloride.

The invention relates to the field of medicines, and in particular discloses a lercanidipine hydrochloride and losartan potassium compound preparation. Particularly, the invention also provides a compound preparation which takes lercanidipine hydrochloride and losartan potassium as basic remedy, takes lactose monohydrate, microcrystalline cellulose, A-type sodium starch glycollate, povidone K30, magnesium stearate, pregelatinized starch and colloidal silicon dioxide as excipients, and takes white Opadry as a coating to prepare a tablet. Clinical tests prove that compared with the single-component preparation, the lercanidipine hydrochloride and losartan potassium compound preparation provided by the invention is remarkably increased in effective rate in light and moderate blood pressures, is remarkably reduced in occurrence rate of adverse effects, and has better clinical application prospect because patients have good tolerance.

The invention relates to a preparation method of lercanidipine. The preparation method comprises the following steps of dissolving 2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridyl-3-carboxylic acid in waterless dichloromethane and waterless dimethylformamide, dropwisely adding thionyl chloride into the solution under control of a temperature in a range of -4 to 1 DEG C, then carrying out stirring for 1h, dropwisely adding an anhydrous methylene chloride solution of 2,N-dimethyl-N-(3,3-dibenzylpropyl)-1-amino-2-ol into the mixed solution at a temperature of -10 to 0 DEG C, then carrying out stirring at a temperature of 0 DEG C for 3h, standing the mixture at a room temperature for 18-20h, carrying out washing orderly by saturated salt water, a sodium carbonate solution with a concentration of 10%, saturated salt water, hydrochloric acid with content of 1mol / L and saturated salt water, adding lercanidipine hydrochloride seed crystals into the washed product, carrying out standing at a temperature of 0-5 DEG C for 1d, carrying out filtration and carrying out anhydrous ethanol re-crystallization to obtain lercanidipine hydrochloride. The preparation method of lercanidipine has the advantages of simple preparation processes, high yield and low cost.

The invention describes novel lercanidipine crude Forms (A) and (B), novel lercanidipine hydrochloride crystalline Forms (I) and (II) obtained from said crude Forms, pharmaceutical, antihypertensive compositions containing as active agent at least one of the lercanidipine hydrochloride crystalline Forms (I) and (II) and methods of use thereof

The invention provides a novel process for the preparation of lercanidipine or a pharmaceutical acceptable salt using novel intermediates. Thus, 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol is reacted with trimethylsilyl chloride in presence of triethyl amine in methylene chloride to give 2,N-dimethyl-2-(trimethylsilyloxy)-N-(3,3-diphenylpropyl)-1-propanamine, which is then reacted with 2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl chloride for 2 hours and crystallized to obtain lercanidipine hydrochloride.

The invention relates to a pharmaceutical composition containing lercanidipine hydrochloride and valsartan as active components and a preparation method thereof. The pharmaceutical composition comprising lercanidipine hydrochloride and valsartan of the present invention has excellent effects on preventing and treating cardiovascular diseases and their concurrent diseases, and reduces the side effects of each component. Furthermore, the composition of the present invention comprises lercanidipine hydrochloride and valsartan in isolated form to increase the dissolution rate of both components and reduce side effects.

The invention provides amorphous lercanidipine hydrochloride and a preparation method thereof. Lercanidipine hydrochloride is a third-generation dihydropyridine calcium antagonist and is mainly used for hypertension and angina in clinic. The invention provides amorphous lercanidipine hydrochloride with the purity being at least 98.5%, particularly at least 99.5% and more particularly at least 99.7%. The invention also provides a preparation method of high-purity amorphous lercanidipine hydrochloride.

The invention provides a pharmaceutical composition for treating hypertension. The invention relates to a pharmaceutical composition comprising therapeutic doses of lercanidipine hydrochloride and enalapril maleate, and a proper amount of oil, a surfactant and an assisted surfactant. Preparative dosage forms particularly hard capsules and soft capsules are provided. The pharmaceutical composition increases solubility of a poorly soluble drug of lercanidipine hydrochloride and stability of enalapril maleate, and is suitable for the treatment of hypertension.

The invention provides a novel process for the preparation of lercanidipine or a pharmaceutical acceptable salt using novel intermediates. Thus, 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol is reacted with trimethylsilyl chloride in presence of triethyl amine in methylene chloride to give 2,N-dimethyl-2-(trimethylsilyloxy)-N-(3,3-diphenylpropyl)-1-propanamine, which is then reacted with 2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl chloride for 2 hours and crystallized to obtain lercanidipine hydrochloride.

Processes for the purification of lercanidipine hydrochloride are provided which uses a binary system of an alcohol-containing solvent such as methanol and an aliphatic ester-containing solvent such as isopropyl acetate. Processes for the preparation of substantially amorphous lercanidipine hydrochloride are also provided. Also provided is lercanidipine hydrochloride substantially in polymorph form V.

The invention provides a novel crystal form of lercanidipine hydrochloride, which has peaks at 5.38 DEG, 10.74 DEG, 11.54 DEG, 11.88 DEG, 15.14 DEG, 17.26 DEG, 17.92 DEG, 19.82 DEG, 20.22 DEG, 20.70 DEG, 21.44 DEG, 21.98 DEG and 22.56 DEG expressed by a 2theta angle in an X ray diffraction pattern. The novel crystal form has high purity (over 99.5 percent) and high stability, has low rigidity and is easy to crush after being dried, and facilitates preparing and using a medicinal composition. The invention also provides a preparation method for the crystal form and a crystal form-containing medicinal composition. Compared with the prior art, the preparation method has the advantages of simple process, mild preparation conditions and high yield.

The invention is a lercandipine hydrochloride crystal (form (HX) crystal) and a preparation method. The crystal has no crystalline water and virgule or crystalline solvent, and is a novel high-purity stable crystalline form, which is more suitable for the large-scale industrial production. The invention has advantages of simple and easy operation, and facilities to prepare the drug combination and provides the clinical use. The crystal uses the Cu-K alpha radiation. The X-ray powder diffraction spectra show expressed in the 2-theta angle has the following characteristics: an angle (2 theta), D(A), a peak relative intensity (%): 7.4, 11.9, 47; 9.6, 9.2, 64; 12.6, 7.0, 32; 13.2, 6.7, 36; 15.7, 5.6, 38; 15.9, 5.6, 63; 17.0, 5.2, 64; 21.4, 4.1, 100; 23.6, 3.8, 87; 5, 3.6, 58.

The present invention relates to a pharmaceutical composition comprising lercanidipine hydrochloride and valsartan as active components and a method for the preparation thereof. The pharmaceutical composition comprising lercanidipine hydrochloride and valsartan according to the present invention has a superior effect on the prevention and treatment of cardiovascular diseases and their complex diseases, and reduces the adverse effects of each component. In addition, the present composition comprises lercanidipine hydrochloride and valsartan in a separated form so as to increase the dissolution rates of both components and reduce the adverse effects.

The invention provides a substantially pure amorphous lercanidipine hydrochloride having a purity of at least 95% pure, preferably at least about 97% pure, more preferably at least about 99% pure, and still more preferably at least about 99.5% pure. The invention further relates to methods of preparing substantially pure amorphous lercanidipine, as well as methods of providing rapid relief from hypertension by administering the substantially pure amorphous lercanidipine hydrochloride of the present invention to a patient in need of such treatment.

Lercanidipine hydrochloride is the third generation of dihydrophridine calcium antagonist and mainly used for treating hypertension and angina clinically. The amorphous lercanidipine hydrochloride is easy to smash, and the purity of the amorphous lercanidipine hydrochloride is at least 98.5%, higher purity is at least 99.5%, and the highest purity is at least 99.7%. The invention further provides a preparation method for the high purity amorphous lercanidipine hydrochloride.

A synthesis process for high-purity lercanidipine hydrochloride is disclosed. The synthesis process comprises the following three steps of: (1) esterifying diketene and 3-hydroxypropionitrile in the presence of an alkali to generate propionitrile acetoacetate; (2) performing condensation and cyclization as well as one-pot hydrolytic acidification on the propionitrile acetoacetate, 3-nitrobenzaldehyde and 3-amido-methyl crotonate to obtain a lercanidipine parent nucleus; and (3) esterifying under the catalysis of thionyl chloride and DMF (dimethyl formamide), and crystallizing to obtain the high-purity lercanidipine hydrochloride. The process disclosed by the invention has the advantages of being simple in steps, moderate and controllable in reaction conditions, high in yield etc.

The present invention describes new lercanidipine hydrochloride crude forms (A) and (B), new lercanidipine hydrochloride crystal forms (I) and (II) obtained from said crude forms, containing at least one lercanidipine hydrochloride crystal form ( I) and (II) antihypertensive pharmaceutical compositions as active agents and methods of use thereof.