Amlodipine crystal, medicine composition of amlodipine crystal and benazepril as well as method for preparing medicine composition

Abstract

The invention relates to an amlodipine crystal, a medicine composition of the amlodipine crystal and benazepril as well as a method for preparing the medicine composition. The amlodipine crystal is a maleic acid amlodipine hydrate crystal, which has a molecular formula as follows: C20H25C12N2O5.C4H4O4.1.5H2O. The medicine composition comprises the following compositions in parts by weight: 2.5-10parts of amlodipine crystal, 10-20 parts of benazepril, 5-50 parts of compressible starch, 20-60 parts of microcrystalline cellulose, 15-40 parts of low-substitution hydroxypropylcellulose, 1-8 partsof sodium carboxymethyl starch, and 1-3 parts of magnesium stearate. The amlodipine in the medicine composition works fast and stably, and can release efficacy stably within 24 hours; and the medicine composition has strong synergism, accumulation and complementary actions, and high bioavailability.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an amlodipine crystal, its medicinal composition with benazepril and a preparation method. Background technique [0002] Benazepril, Chinese alias: (3s)-3-{[((1s)-1-ethoxycarbonyl)-3-phenylpropyl]amino}-2,3,4,5-tetrahydro-2 -Oxo-1H-1-benzoazepine-1-acetic acid, English name: Benazepril, molecular formula: C 24 h 28 N 2 o 5 , molecular weight: 424.49, the structural formula is as follows: [0003] [0004] Benazepril is a prodrug, and benazepril is hydrolyzed into benazeprilat in the liver, becoming a competitive angiotensin-converting enzyme inhibitor. Benazepril prevents the inactive angiotensin I from being converted into angiotensin II by inhibiting angiotensin-converting enzyme, thereby reducing the production of angiotensin II and exerting antihypertensive effect. Benazepril can also increase the level of bradykinin, increase the release of nitric oxide...

AI Technical Summary

Problems solved by technology

[0011] In the prior art, amlodipine and amlodipine salts (such as amlodipine maleate, amlodipine besylate, amlodipine mesylate, etc.) are almost insoluble in water and are slowly absorbed in the human body. The peak blood concentration is reached within 6 to 12 hours, and the overall level of blood concentration is low, especially the initial blood concentration after administration is very low. The peak concentration of the drug, the drug has a fast onset of action, and the time difference between the two drugs when they reach the peak plasma concentration after simultaneous administration is far away, and the synergistic, additive, and complementary effects are very limited

For example, Chinese patent CN101653440A discloses a composition containing amlodipine salt and pril-like drugs, and said amlodipine salt includes hydrochloride, camphorate, pyroglutamate, L-aspartate And mesylate, these amlodipine salts can improve the solubility and high temperature stability of amlodipine in the composition, but its solubility is still very small, in addition, the time for its blood drug concentration to reach the peak has not changed, the medicinal After the administration of the composition, amlodipine still takes a slow onset of action, and the synergistic effect of amlodipine and puril drugs is very limited

[0012] In addition, in order to improve the bioavailability of amlodipine salt, the prior art uses the amlodipine salt of the racemate to be split into levamlodipine salt. After the administration of levamlodipine salt, although the bioavailability is somewhat However, the time to reach the peak blood concentration is still 6 to 12 hours, and the onset of effect is slow. After administration according to the dose required by the normal human body, the initial blood concentration is very low, and its synergy, accumulation and complementarity with benazepril very limited

For example, Chinese patent CN101229161A discloses a pharmaceutical composition formed by mixing levamlodipine and benazepril or the pharmaceutical salts of these two drugs with pharmaceutically acceptable adjuvants. Amlodipine has a slow onset of action and very limited synergy between levoamlodipine and benazepril

And, amlodipine salt is split into levamlodipine salt, which increases the production process, and in the process of splitting, there is loss of dexamlodipine salt and the introduction of impurities, which greatly increases the cost of medicine

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