35 results about "Trandolapril" patented technology

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.

The invention relates to a method for preparing a trandolapril intermediate in the field of biomedicines, i.e. a method for synthesizing (2S, 3aR, 7aS)-octahydroindole-2-carboxyl benzyl ester. Firstly, cyclohexene and chloramine T are taken as initial raw materials to react so that cyclohexane ethylene imine is obtained; cyclohexane ethylene imine and allylmagnesium bromide are reacted with each other to obtain trans-N-(p-toluene sulphonyl)-2-(2-allyl)-cyclohexylamine which is peroxidized so as to obtain racemic N-protecting octahydroindole-2-carboxylic acid under the action of an oxidizing agent; after a protecting group on nitrogen is removed, racemic octahydroindole-2-carboxyl benzyl ester is obtained through esterification reaction; and the racemic octahydroindole-2-carboxyl benzyl ester is recrystallized and separated to obtain the trandolapril key intermediate (2S, 3aR, 7aS)-octahydroindole-2-carboxyl benzyl ester. According to the method, raw materials are low in cost and easy to obtain, the preparation process is environmental-friendly, the operation and post-treatment are simple, separation and purification are easy and the like.

A process for the synthesis of trandolapril which comprises condensing N-[I-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride with trans octahydro-1H-indole-2-carboxylic acid in a first organic solvent comprising a water immiscible inert organic solvent and in the presence of a base, and isolating trandolapril from a second organic solvent. N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride may also be condensed with (2S,3aR,7aS) octahydro-1H-indole-2-carboxylic acid in a first organic solvent and in the presence of a base, and trandolapril isolated. There is also provided a process for the resolution of racemic trans octahydro-1H-indole-2-carboxylc acid.

The invention which belongs to the technical field of medicines relates to a trandolapril capsule and a preparation process thereof. The trandolapril capsule comprises trandolapril and lactose according to a weight ratio of 1:60-1:180, wherein lactose is used as a diluent. The preparation process adopts partial wet granulation, main medicine addition, and capsule filling. The invention aims to provide the trandolapril capsule with the characteristics of stable and reliable quality, and simple and feasible process.

The invention discloses a preparation method of trandolapril midbody (2S, 3aR, 7aS)-octahydro-1H-indole-2-carboxylic acid, and the preparation method comprises the following steps of: preparing 3-chlorine-2-amino-propionic acid methyl ester hydrochloride by using phosphorous pentachloride and dichloromethane; preparing 3-chlorine-2-acetyl amino-propionic acid methyl ester hydrochloride by using the 3-chlorine-2-amino-propionic acid methyl ester hydrochloride, methylbenzene and acetyl chloride; preparing 2,3,4,5,6,7-hexahydro-1H-indole-2-carboxylic acid by using the 3-chlorine-2-acetyl amino-propionic acid methyl ester hydrochloride, DMF (Dimethyl Formamide) and 1-pyrrole cyclohexene; preparing (2S)-octahydro-1H-indole-2-methyl carboxylat by using the 2,3,4,5,6,7-hexahydro-1H-indole-2-carboxylic acid, methanol and palladium on carbon; preparing the (2S, 3aR, 7aS)-octahydro-1H-indole-2-carboxylic acid by using the (2S)-octahydro-1H-indole-2-methyl carboxylat and the methanol. Compared with the prior art, the preparation method of the trandolapril midbody (2S, 3aR, 7aS)-octahydro-1H-indole-2-carboxylic acid, which is disclosed by the invention, has the advantages of easiness and convenience for process, easiness for control, safety, reliability and low cost.

The invention provides a mass spectrometry method for identifying personalized medication of trandolapril through product detection. The method includes the steps: designing multiple-amplification primers and extension primers separately according to multiple to-be-detected target SNP sites, preparing a multiple amplification primer reaction system and an extension primer reaction system, performing amplification and single-base extension reactions at the target SNP sites simultaneously through multiple sets of primers in the reaction systems, performing time-of-flight mass spectrometry analysis of products obtained after the single-base extension reactions so as to identify the genotypes of SNP related to metabolism of different drugs, and guiding personalized medication of the antihypertensive drug trandolapril. Five SNP sites related to metabolism of the trandolapril drugs can be detected simultaneously, and the method has the advantages of low cost, no needs for synthetic probes, short time consumption, simple and convenient result analysis and extremely wide application fields, and can be applied to auxiliary diagnosis and treatment of hypertensive patients who need to take trandolapril clinically.

The invention provides a medication method and reagent kit of a hypertension reducing medicine namely trandolapril. The medication method comprises the steps of according to multiple objective SNP sites to be detected, respectively designing a multiplex amplification primer and an extension primer; compounding a multiplex amplification primer reaction system and an extension primer reaction system; in the reaction systems, performing amplification and a single-base extension reaction on the objective SNP sites at the same time with multiple sets of primers; and performing flight time mass spectrometric analysis on products after being subjected to the single-base extension reaction, identifying the genotypes of different drug metabolism relevant SNPs according to products of different molecular weight extension primers represented by mass spectrum peaks, and guiding the medication of the hypertension reducing medicine namely the trandolapril. Besides, the invention provides a detectionreagent kit using the method. According to the medication method disclosed by the invention, 5 trandolapril drug metabolism pertinent SNP sites can be detected at the same time, and the medication method has the advantages of being low in cost, free from synthetized probes, short in time consumption, simple and convenient in result analysis, and extremely broad in application field.

The invention provides a method for carrying out mass-spectrography distinguishing on trandolapril individualized medicine application through a primer composition. The method comprises the followingsteps of: according to a plurality of objective SNP sites to be detected, independently designing a multiplex amplification primer and an extension primer; preparing a multiplex amplification primer reaction system and an extension primer reaction system; in the reaction systems, adopting multiple sets of primers to simultaneously independently carry out amplification and single-base extension reaction on the plurality of objective SNP (single nucleotide polymorphism) sites; and carrying out flight time mass spectrometry on a product subjected to the single-base extension reaction, identifyingthe genotypes of different medicine metabolism related SNPs, and guiding the individualized medicine application of a hypertension lowering medicine, i.e., the trandolapril. The method disclosed by the invention can simultaneously detect five trandolapril medicine metabolism related SNP sites, has the advantages of low cost, short time consumption, simple and convenient result analysis and wide application ranges, does not need to carry out probe synthesis, and can be used for the auxiliary diagnosis and treatment of a hypertension patient who clinically needs to take the trandolapril.

The invention provides a primer composition for distinguishing an individualized medication type of an antihypertensive drug trandolapril. A preparation method of the primer composition comprises thefollowing steps: multiple amplification primers and extension primers for multiple to-be-detected target SNP loci respectively; a multiple amplification primer reaction system and an extension primerreaction system are prepared; in the reaction systems, amplification and single-base extension reaction is conducted simultaneously and respectively for the multiple target SNP loci by using multipleprimers; and products obtained after the single-base extension reaction are subjected to time-of-flight mass spectrometry (TOF MS) analysis to identify genotypes of different SNPs related to drug metabolism and guide individualized medication of the antihypertensive drug trandolapril. The primer composition can detect five SNP loci related to trandolapril drug metabolism simultaneously, has the advantages of low cost, no synthesis probe, short time, simple and convenient result analysis and very wide application fields, and can be applied to auxiliary diagnosis and therapy of hypertension patients needing to take trandolapril clinically.

The invention discloses a preparation method of an isomer of a trandolapril intermediate, and in particular discloses a preparation method of the isomer of the trandolapril intermediate which is shown in a formula C and is acquired by using (R,S,S)-octahydroindole-2-carboxylic acid (shown in a formula A) as an initial raw material with the content of more than 90 percent, performing configuration turning and upper benzyl protection to obtain isomer mixtures C and D of the corresponding trandolapril intermediate and performing separation again. According to the technical scheme, the formula A is subjected to configuration turning, and the content of a compound of the formula B is obviously increased, so that the isomers of the subsequent other intermediates are greatly prepared, and the compound is used for preparing medicines for resisting cardiovascular disease and controlling the quality of the medicines.

The invention relates to a pharmaceutical composition containing a trandolapril taste masking composition. The pharmaceutical composition is prepared from, by weight, 60-80 parts of the trandolapril taste masking composition, 10-20 parts of filler, 5-9 parts of adhesive, 6-8 parts of disintegrant and 4-6 parts of lubricant, wherein the trandolapril taste masking composition is formed by mixing mannitol, gelatin, disodium glycyrrhizunate and trandolapril by the ratio of 20:20:0.1:1, and the disintegrant is a mixture of croscarmellose and polyvinylpolypyrrolidone by the mass ratio of (1.3-1.7):1. The pharmaceutical composition has the advantages of being capable of greatly improving the mouthfeel, and the disintegration speed of the pharmaceutical composition is increased.

The invention relates to a trandolapril-containing pharmaceutical composition. The composition is prepared from, by weight, 1-2 parts of trandolapril, 10-60 parts of a filling agent, 5-45 parts of adhesives, 4-36 parts of a disintegrating agent, 2-10 parts of a flow aid and 4-6 parts of a lubricating agent, wherein the lubricating agent is a mixture of cinnamyl magnesium sulfate and magnesium stearate in a weight ratio of 1:1.7-2.1. The trandolapril-containing pharmaceutical composition has advantages that by synergistic effects and strict control of ratios of components, efficacies of the pharmaceutical composition is greatly improved; in addition, stability and controllability in quality and safety and effectiveness in clinical application are realized, and the pharmaceutical composition can be completely disintegrated in water within 2min and is convenient to store, transport and carry.

A process for the preparation of (2S,3aR,7aS)-octahydro-1H-indole-20carboxylic acid hydrochloride.