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

A technology of amlodipine and dipine hydrate, which is applied in the field of medicine, can solve the problems of limited synergistic effect, synergy, accumulation and complementary effect of levamlodipine and benazepril, and slow onset of effect of levamlodipine, etc. Achieve the effect of improving bioavailability, good disintegration performance and dissolution rate, stable and long-lasting drug effect

Active Publication Date: 2012-02-08
HAINAN JINRUI PHARMA
View PDF4 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Amlodipine crystal, medicine composition of amlodipine crystal and benazepril as well as method for preparing medicine composition
  • Amlodipine crystal, medicine composition of amlodipine crystal and benazepril as well as method for preparing medicine composition
  • Amlodipine crystal, medicine composition of amlodipine crystal and benazepril as well as method for preparing medicine composition

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0052] Example 1

[0053] Dissolve amlodipine maleate in a mixed solvent of dimethyl sulfoxide / deionized water, adjust the pH to 6 with 1mol / L HCl or 1mol / L NaOH, apply 40KHz ultrasonic waves, stir and heat up to 80°C, Incubate and stir for 2~3h, add 80℃ deionized water, a white crystalline product precipitates, cool to 0℃, filter, wash with dichloromethane, and vacuum dry for 3h to obtain amlodipine maleate hydrate crystals. The particle size range is 75~150μm, mp: 156~158℃.

[0054] Using the PE 2400 II elemental analyzer from Perkin-Elmer Company, the calculated value of elemental analysis (%): C(52.22), H(5.84), Cl(6.42), N(5.08), O(30.44); elemental analysis ( %) Measured value: C (52.25), H (5.88), Cl (6.39), N (5.06), O (30.42).

[0055] Using PE Pyris Diamond TG thermal analyzer from Perkin-Elmer, USA, the thermogravimetric analysis experiment shows (see figure 2 ): The curve of the amlodipine maleate hydrate crystals prepared in Example 1 at a temperature between 25 and 5...

Example Embodiment

[0057] Example 2

[0058] Dissolve amlodipine maleate in a mixed solvent of dimethyl sulfoxide / deionized water, adjust the pH to 6.5 with 1mol / L HCl or 1mol / L NaOH, apply 40KHz ultrasonic waves, stir and heat up to 80°C, Incubate and stir for 2 hours, add 80°C deionized water, white crystalline product precipitates, cool to 5°C, filter, wash with dichloromethane, and vacuum dry for 2 hours to obtain amlodipine maleate hydrate crystals. The crystal size The range is 75~150μm, mp: 156~158℃.

[0059] Using the PE 2400II elemental analyzer from Perkin-Elmer, USA, the calculated value of elemental analysis (%): C(52.22), H(5.84), Cl(6.42), N(5.08), O(30.44); elemental analysis (%) ) Measured value: C (52.26), H (5.83), Cl (6.39), N (5.06), O (30.46).

[0060] Using PE Pyris Diamond TG thermal analyzer from Perkin-Elmer, USA, the TG-time curve obtained is consistent with that of Example 1.

[0061] The X-ray powder diffraction pattern measured by using Cu-Kα rays is consistent with that o...

Example Embodiment

[0062] Example 3

[0063]

[0064] Are made into 1000 pieces

[0065] Preparation:

[0066] The raw and auxiliary materials were crushed through an 80-mesh sieve, the microcrystalline cellulose and amlodipine maleate hydrate crystals were mixed, and then mixed with benazepril, compressible starch, low-substituted hydroxypropyl cellulose and carboxymethyl The sodium starch is mixed uniformly, and then mixed with magnesium stearate for 5 minutes, the intermediate is tested, and the composition is obtained by direct compression.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Particle sizeaaaaaaaaaa
Mpaaaaaaaaaa
Login to view more

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...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D211/90A61K31/55A61K31/4422A61K9/28A61K47/36A61K47/38A61K47/12A61P9/00A61P9/12A61P9/10
Inventor 马鹰军王小树钟正明罗韬
Owner HAINAN JINRUI PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap