Amlodipine and losartan potassium medicinal composition and preparation method thereof

Abstract

The invention relates to an amlodipine and losartan potassium medicinal composition, which comprises the following components calculated according to weight part: 2.5-10 parts of amlodipine, 20-100 parts of losartan potassium, 5-20 parts of pregelatinized starch, 20-60 parts of microcrystalline cellulose, 15-40 parts of low substitution hydroxypropyl cellulose, 1-8 parts of carboxymethyl starch sodium and 1-3 parts of magnesium stearate. The amlodipine is an amlodipine maleate hydrate crystal with a molecular formula of C24H29ClN2O9.1.5H2O. The amlodipine maleate in the medicinal composition can be used for stably releasing the medicinal effect within 24 hours and stably and quickly taking effect. The medicinal composition has strong synergism, accumulation and complementary action and high bioavailability.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to amlodipine and its medicinal composition with losartan potassium and a preparation method thereof. Background technique [0002] Losartan potassium, Chinese alias: 2-butyl-4-chloro-5-(hydroxymethyl)-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl ] Potassium imidazole, English name: Losartan potassium, molecular formula: C22H22CIKN6OK, molecular weight: 461.01, structural formula is as follows: [0003] [0004] Losartan potassium is a new type of non-peptide angiotensin II receptor (AT1) antagonist, which can lower blood pressure, improve heart failure, and prevent and treat hypertension complicated by thickening of blood vessel walls and cardiac hypertrophy. It has the effect of maintaining the kidneys, increasing renal blood flow, glomerular filtration rate, increasing the excretion of urine, urinary sodium and uric acid, and reducing the secretion of adrenal ald...

AI Technical Summary

Problems solved by technology

[0010] 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 drug concentration is reached within 6-12 hours, and the overall level of blood drug concentration is low, especially the initial blood drug concentration after administration is very low. The drug concentration reaches the peak blood concentration in 1 hour and 3-4 hours respectively, and the drug effect is fast. After the two drugs are administered at the same time, the time when they reach the peak blood concentration is far away, and the synergistic, cumulative and complementary effects very limited

For example, Chinese patent CN101472587A discloses a composition for preventing or treating cardiovascular diseases, which comprises amlodipine or a pharmaceutically acceptable salt thereof and losartan or a pharmaceutically acceptable salt thereof, the invention Improved the dissolution rate and stability of amlodipine and losartan potassium, but amlodipine is still slow to act, and the synergistic effect of the two is very limited

[0011] 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 6-12 hours, and the onset of effect is slow. The initial blood concentration after administration according to the dose required by the normal human body is very low, and its synergistic, cumulative and complementary effect with losartan potassium very limited

For example, Chinese patent CN1883478 discloses a pharmaceutical composition for treating hypertensive cardiovascular disease, comprising levamlodipine and losartan, and discloses that the pharmaceutical composition can be made into tablets, granules, capsules, Injection, sustained-release preparation, the invention improves the chemical stability and solubility of the drug, but the initial blood concentration of amlodipine salt is low after administration, and the onset of effect is slow, and its synergistic effect with losartan is very limited

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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