Amlodipine and candesartan pharmaceutical composition and preparation method thereof

Abstract

The invention relates to an amlodipine and candesartan pharmaceutical composition. The pharmaceutical composition comprises the following components in parts by weight: 2.5-5 parts of amlodipine hydrate crystal, 4-16 parts of candesartan, 5-50 parts of compressible starch, 10-60 parts of microcrystalline cellulose, 15-40 parts of low-substituted hydroxypropyl cellulose, 10-45 parts of cross-linked polyvinyl pyrrolidone and 1-3 parts of magnesium stearate, wherein the amlodipine is amlodipine maleate hydrate crystal with a molecular formula of C24H29ClN2O9.1.5H2O. The pharmaceutical composition has the advantages that: amlodipine maleate has rapid and stable action, and can be stably released within 24 hours; and the pharmaceutical composition has strong synergism, accumulation and complementation effects, and has high bioavailability.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a pharmaceutical composition of amlodipine and candesartan cilexetil and a preparation method thereof. Background technique [0002] Candesartan cilexetil, Chinese alias: (±)-1-[[(cyclohexyloxy)carbonyl]oxo]ethyl-2-ethoxy-1-[[2′-(1H-tetrazolium Base-5)-[1,1′-biphenyl]-4-yl]methyl]-1H-benzimidazole-7-carboxylate, English name: Candesartan cilexetil, molecular formula: C33H34N6O6, molecular weight: 610.67, The structural formula is as follows: [0003] [0004] Candesartan cilexetil is rapidly hydrolyzed into the active metabolite candesartan in the body. Candesartan is a selective angiotensin II receptor (AT1) antagonist that antagonizes vascular tension by binding to vascular smooth muscle AT1 receptors The vasoconstriction effect of factor II, thereby reducing the peripheral vascular resistance. It is also believed that candesartan can exert a certain antihype...

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. Reach the peak concentration of the blood concentration, the drug has a rapid onset of action, and the time difference between the two drugs when they reach the peak blood concentration after simultaneous administration is far away, and the synergistic, cumulative and complementary effects are very limited

For example, Chinese patent CN101371834A discloses a pharmaceutical composition containing amlodipine besylate and candesartan cilexetil, the weight ratio of amlodipine besylate and candesartan cilexetil is 1: 1-6, the The pharmaceutical composition has a certain synergistic effect in lowering blood pressure and dilating blood vessels, but the onset of amlodipine besylate is slow, and the synergistic effect of the pharmaceutical composition of amlodipine besylate and candesartan cilexetil is 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 to 12 hours, and the onset of effect is slow. The initial blood concentration is very low after administration according to the dose required by the normal human body. The synergistic, cumulative, and Complementarity is very limited

Chinese patent CN102106853A discloses a medicinal composition for treating hypertension, the active ingredients of which are amlodipine besylate and candesartan cilexetil. The composition treats hypertension with a lower dosage than the single prescription, and has a synergistic effect. However, amlodipine levobesylate has a slow onset of action, and the synergistic effect of the two 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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