62 results about "Ramipril" patented technology

A pharmaceutical composition comprising a solid unit dosage form comprising: one or more of pharmaceutically active ingredients selected from valacyclovir, olanzapine, voriconazole, topotecan, artesunate, amodiaquine, guggulosterone, ramipril, telmisartan, tibolone, atorvastatin, simvastatin, amlodipine, ezetimibe, fenofibrate, tacrolimus, valgancyclovir, valsartan, clopidrogel, estradiol, trenbolone, efavirenz, metformin, pseudoephedrine, verapamil, felodipine, valproic acid/sodium valproate, mesalamine, hydrochlorothiazide, levosulpiride, nelfinavir, cefixime and cefpodoxime proxetil in combination with a water insoluble polymer and/or a water soluble polymer. Methods for making the pharmaceutical composition are also disclosed.

A process for preparing ramipril, and stable pharmaceutical compositions containing ramipril.

A stable pharmaceutical composition comprising about 1 wt. % to about 80 wt. % of an ACE inhibitor or a pharmaceutical acceptable salt thereof, about 1 wt. % to about 70 wt. % of an alkali or alkaline earth metal carbonate, and about 1 wt. % to about 80 wt. % of hydroxypropyl cellulose, wherein the ACE inhibitor is selected from the group consisting of quinapril, enalapril, spirapril, ramipril, perindopril, indolapril, lisinopril, alacepril, trandolapril, benazapril, libenzapril, delapril, cilazapril and combinations thereof; wherein the formation of an internal cyclization product, and/or ester hydrolysis product, and/or oxidation product, has been reduced or eliminated, and the weight percents are based on the total weight of the pharmaceutical composition. The stabilized pharmaceutical compositions of the invention exhibit a number of advantages as follows: (i) the ACE inhibitor or a pharmaceutical acceptable salt thereof present in the compositions is preserved from degradation; (ii) the compositions exhibit extended shelf-life under normal storage conditions; (iii) the effect of moisture on the compositions is minimized; (iv) the compositions exhibit minimal, if any, discoloration over a significant period of time; and (v) the compositions exhibit minimal, if any, instability when employed in the presence of colorants.

A stable oral pharmaceutical formulation comprising ramipril or its pharmaceutically acceptable salt and a stabilizing amount of an ammoniomethacrylate copolymer in a pharmaceutically acceptable carrier medium is described.

The present invention relates to a stable pharmaceutical composition comprising an ACE inhibitor or a pharmaceutically acceptable salt or derivative thereof. In particular, the invention relates to a pharmaceutical composition, which comprises an ACE inhibitor, or a pharmaceutically acceptable salt or a derivative thereof, and a C₁₆-C₂₈ glyceride. ACE inhibitors useful in the present invention are susceptible to heat and/or mechanical stress-induced degradation. Preferred ACE inhibitors are ramipril, trandolapril, quinapril and pharmaceutically acceptable salts and derivatives thereof. The composition of the present invention may be for use as a medicament for the treatment or prevention of a cardiovascular disease, a coronary heart disease, a cerebrovascular disease, a peripheral vascular disease, arrhythmia, hypertension, cardiac failure, cardiovascular death, myocardial infraction, stroke or angina. The present invention further relates to a method of preparing the pharmaceutical composition of the present invention. The present invention also relates to a method of providing a stable pharmaceutical composition comprising an ACE inhibitor, or a pharmaceutically acceptable salt or derivative thereof, by incorporating a C₁₆-C₂₈ glyceride into the composition. The present invention further relates to a use of C₁₆-C₂₈ glyceride to provide a stable pharmaceutical composition comprising an ACE inhibitor or a pharmaceutically acceptable salt or derivative thereof.

A Ramipril formulation rapidly disintegrates after ingestion and exhibits substantially no food effect.

A process for preparing an enantiomerically enriched cycloalkene-substituted alanine compound having the structure:

by asymmetrically hydrogenating a dehydro amino acid compound having the structure:

in a suitable reaction media in the presence of a catalyst having a transition metal moiety complexed to a chiral phosphine ligand to prepare enantiomerically enriched cycloalkene substituted alanine compounds having the structure of Formula (IA) or (IB), which are key intermediates for the ACE inhibitors ramipril and perindolpril:

A composition for transdermal administration resulting from an admixture includes: a therapeutically effective amount of a drug that includes a parent drug and a prodrug; and a pharmaceutically acceptable carrier, wherein the parent drug and prodrug are individually present in an amount sufficient for a pharmacological effect. In a preferred embodiment, the admixture includes: a therapeutically effective amount of a pharmaceutically active agent that includes a corresponding steroid and a steroid derivative; and a carrier for the pharmaceutically active agent. The steroid and the corresponding steroid derivative are present in a weight ratio of 10:1 to 1:10 steroid:corresponding steroid derivative. In a preferred embodiment ratio is 6:1 to 1:6. In a preferred embodiment, the corresponding steroid derivative is a steroid ester. In another preferred embodiment, the carrier is a polymer that includes a pressure-sensitive adhesive. In another preferred embodiment, the parent drug is an ACE inhibitor such as ramipril and the prodrug is an ACE inhibitor prodrug such as ramipril ethyl and/or methyl ester.

The invention relates to a synthesizing method using serine to prepare a Ramipril key intermediate. The Ramipril key intermediate is 2-azabicyclo[3.3.0] octane-3-carboxylic acid hydrochloride or benzyl ester hydrochloride. The synthesizing method includes: using the serine as the initial raw material, and sequentially performing esterification, acyl chloride acylation, deacidification, Michael addition, hydrolysis and hydrogenation reduction to obtain the Ramipril key intermediate. The synthesizing method has the advantages that the key intermediate is synthesized by a five-step method, and the synthesizing method is cheap in raw material, environmentally friendly, simple in preparation process, simple to operate, mild in reaction condition, short in reaction cycle, convenient in post-treatment, low in equipment requirement, capable of avoiding heavy metal pollution and the use of expensive catalysts, few in three wastes, high in product yield and purity and suitable for industrial production.

A composition for transdermal administration resulting from an admixture includes: a therapeutically effective amount of a drug that includes a parent drug and a prodrug; and a pharmaceutically acceptable carrier, wherein the parent drug and prodrug are individually present in an amount sufficient for a pharmacological effect. In a preferred embodiment, the admixture includes: a therapeutically effective amount of a pharmaceutically active agent that includes a corresponding steroid and a steroid derivative; and a carrier for the pharmaceutically active agent. The steroid and the corresponding steroid derivative are present in a weight ratio of 10:1 to 1:10 steroid: corresponding steroid derivative. In a preferred embodiment ratio is 6:1 to 1:6. In a preferred embodiment, the corresponding steroid derivative is a steroid ester. In another preferred embodiment, the carrier is a polymer that includes a pressure-sensitive adhesive. In another preferred embodiment, the parent drug is an ACE inhibitor such as ramipril and the prodrug is an ACE inhibitor prodrug such as ramipril ethyl and/or methyl ester.

The invention relates to a kind of chemosynthesis method of N-[1(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine-N-hydroxy acid anhydride, which is the medicine midbody for synthesizing Pulitzer series medicine such as Enalapril, Ramipril, Lisinopril and so on. The invention uses couple (trichloromethyl) ester carbonate and N-[1(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine as row material, and get the product by reacting with catalyst action in organic solvent. This chemosynthesis method is a manufacturing method of N-[1(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine-N-hydroxy acid anhydride, which has acquirable raw material, low production cost, and no three wastes normally.

The present invention relates to stable tablet formulations of ramipril, optionally in combination with a diuretic.

A pharmaceutical composition comprising ramipril, another active agent, and a blending agent, wherein in the ramipril is coated by the blending agent, and wherein the blending agent is glyceryl behenate, glyceryl stearate, stearyl alcohol, macrogol stearate ether, palmitosearate, ethylene glycol, polyethylene glycol, stearic acid, cetyl alcohol, lauryl alcohol, amylopectin, poloxymer or combinations thereof.

The invention discloses a compound sustained-release preparation containing felodipine and ramipril and a preparation method of the compound sustained-release preparation, wherein the compound sustained-release preparation is prepared by mixing felodipine sustained-release pellets and ramipril immediate-release pellets according to a specific dose proportion. The felodipine sustained-release pellets can sustainably release for 12 hours, and can be taken once a day, so as to keep the antihypertensive effect for a long time, the ramipril immediate-release pellets can be quickly absorbed so as to achieve the antihypertensive effect and treat the plasma concentration, due to the combination of the two kinds of pellets, the antihypertensive effect can be greatly enhanced, the toxic and side effect of the medicine can be reduced, the administration frequency can be reduced, sustainably stable antihypertensive effect can be achieved in a human body, the patient compliance can be enhanced, the compound sustained-release preparation consists of hundreds and thousands of pellets in uniform particle sizes, so that the damage of individual pellets will not cause burst release of the whole preparation, and compared with the sustained release tablets, the compound sustained-release preparation disclosed by the invention has the advantages of higher safety, lower irritation to gastrointestinal tract, more stable plasma concentration and capability of effectively improving the clinical effect.

The invention relates to a large-scale industrialized preparation method of ramipril. The preparation method includes following steps; (1) performing a reaction directly from a compound (s,s,s)-2-azobicyclo[3,3,0]octane-3-carboxylic acid derivative and N-[1-(s)-ethoxycarbonyl-3-phenylpropyl]-L-alanine under action of a condensation reagent; and (2) performing catalytic hydrogenation deprotection and a purifying process to obtain the ramipril. In the preparation method, by means of optimization of technology conditions, generation of impurities can be reduced and a DCU residual problem can be solved. The preparation method is more than 60% in total yield and can reach a HPLC detected purity of 99.95%.

The invention discloses a synthesis method of a ramipril key intermediate. The ramipril key intermediate is 2-azabicyalo [3.3.0] octane-3-carboxylic acid hydrochloride. The 2-azabicyalo [3.3.0] octane-3-carboxylic acid hydrochloride is obtained through sequential dehydration cyclization, formaldehyde condensation, hydrolysis, removal, Michael addition, cyclization and palladium-carbon catalytic hydrogenation reduction of N-benzoyl-glycine as a raw material. According to the synthesis method of the ramipril key intermediate, the required raw material and reagent are cheap and available, the yield is relatively high, the operation is simple, the cost is low and the method is suitable for industrial production.

A method of treating pulmonary hypoplasia in infants has been developed, wherein epidermal growth factor (EGF) is administered to the pulmonary system of an infant in need of treatment thereof. The EGF is administered as an aerosol or dry powder directly to the pulmonary tree, or into the amniotic fluid before birth if a situation such as oligohydramnios is recognized pre-term. The method can also be used to treat persistent pulmonary hypertension of the newborn. A hydrophobic angiotensin I-converting enzyme (ACE) inhibitor such as ramipril can also be used for the oral treatment of persistent pulmonary hypertension of the newborn.