CN101401942B - Azelnidipine composition - Google Patents
Azelnidipine composition Download PDFInfo
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- CN101401942B CN101401942B CN2008101597669A CN200810159766A CN101401942B CN 101401942 B CN101401942 B CN 101401942B CN 2008101597669 A CN2008101597669 A CN 2008101597669A CN 200810159766 A CN200810159766 A CN 200810159766A CN 101401942 B CN101401942 B CN 101401942B
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- azelnidipine
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- ethyl acetate
- schardinger dextrin
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Abstract
The invention discloses an Azelnidipine composition, which consist of Azelnidipine and beta-cyclodextrin, wherein the dosage by weight of the beta-cyclodextrin is 3 to 15 times of that of the Azelnidipine, and the Azelnidipine is enveloped in a hydrophobic cavity of the cyclodextrin. The bioavailability of the Azelnidipine composition is obviously improved compared with a common preparation of the Azelnidipine, which lays a foundation for further development of a new oral preparation of the Azelnidipine.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition of dihydropyridine calcium ion antagonist, relate in particular to a kind of azelnidipine composition and method of making the same and preparation purposes.
Background technology
Sickness rate, the case fatality rate of China's heart brain and kidney blood vessel diseases rise year by year, and the trend of rejuvenation is gradually arranged.Azelnidipine is a dihydropyridine calcium ion antagonist, can suppress vascular smooth muscle cell transmembrane potential dependency L type calcium channel by specificity, flow in the cell from the extracellular by suppressing calcium ion, cause the vascular smooth muscle diastole and produce the blood vessel dilating effect, thereby cause hypotensive activity.Controlling blood pressure increases cardiac output reposefully, and is very little to the influence of heart rate, do not cause reflex tachycardia.Thereby azelnidipine is specially adapted to the hyperpietic's of potential heart ischemia long-term treatment.
Azelnidipine
Yet, find that in the research of the oral formulations of azelnidipine with in using its bioavailability is lower, ordinary preparation need add surfactant such as tween-80 could improve bioavailability.Because tween is an oiliness compound, this brings difficulty for the production of azelnidipine solid preparation.
Summary of the invention
At the deficiency that existing azelnidipine oral formulations exists, the problem to be solved in the present invention provides a kind of oral azelnidipine compositions that is suitable for of the bioavailability that can improve azelnidipine significantly.
Azelnidipine compositions of the present invention is characterized in that: described compositions is made up of azelnidipine and beta-schardinger dextrin-, and wherein the consumption of beta-schardinger dextrin-is 3～15 times of azelnidipine in weight ratio.
Further optimal way is: described compositions is made up of azelnidipine and beta-schardinger dextrin-, and wherein the consumption of beta-schardinger dextrin-is 5～10 times of azelnidipine in weight ratio.
Most preferred embodiment is: described compositions is made up of azelnidipine and beta-schardinger dextrin-, and wherein the consumption of beta-schardinger dextrin-is 5～7 times of azelnidipine in weight ratio.
Wherein:
Above-mentioned azelnidipine forms compositions with the form and the beta-schardinger dextrin-of envelope in the beta-schardinger dextrin-hydrophobic internal cavities.
The character of above-mentioned beta-schardinger dextrin-: white crystals or crystalline powder, odorless, it is little sweet to distinguish the flavor of; Differentiate: be positive reaction; Clarity of solution and color: clarification, colourless; Feature optical activity :+159----+164.
7 D of beta-schardinger dextrin-(+)-glucopyranose is with α-1, and the 4-glycosidic bond joins end to end and forms.All hydroxyls of its molecule come the molecule outside, form the tubular hydrophobic environment of hollow, small-molecule drug easily envelope in the beta-schardinger dextrin-inner chamber, thereby provide platform for improving bioavailability of medicament.
The molecular structural formula of azelnidipine compositions of the present invention is as follows:
Azelnidipine preparation of compositions method of the present invention is characterized in that: with azelnidipine ethyl acetate stirring and dissolving, add beta-schardinger dextrin-then and be stirred to pasty state, remove ethyl acetate and obtain the azelnidipine compositions under 50 ± 1Pa.
A kind of oral formulations of azelnidipine wherein contains the azelnidipine compositions of the present invention and the pharmaceutically acceptable carrier that is used to prepare oral formulations for the treatment of effective dose.
Wherein: described oral formulations is one of tablet, capsule, electuary; Described carrier preferred starch, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, calcium hydrogen phosphate and/or the lactose that is used to prepare oral formulations.
Further preferred embodiment is: oral formulations of the present invention is a tablet, and wherein the prescription of tablet is as follows in the weight portion proportioning:
Azelnidipine compositions 48
Microcrystalline Cellulose 30
Starch 20
Low-substituted hydroxypropyl cellulose 10
Magnesium stearate 1.1.
Experimental results show that: azelnidipine compositions of the present invention can improve the bioavailability of azelnidipine significantly.
Through the rat pharmacokinetics relatively; the bioavailability of azelnidipine compositions of the present invention is 42.2%; and the bioavailability of commercially available azelnidipine only is 22.1%; the bioavailability that azelnidipine compositions of the present invention is described is obviously improved than the ordinary preparation of azelnidipine; for the oral formulations of further development of new azelnidipine is laid a good foundation, while azelnidipine preparation of compositions pattern of the present invention also is that the large-scale production of the oral formulations of azelnidipine has alleviated difficulty.
The specific embodiment
Embodiment 1
The azelnidipine preparation of compositions
Azelnidipine 8g, ethyl acetate 50ml after the stirring and dissolving, adds beta-schardinger dextrin-40g, is stirred to pasty state, removes ethyl acetate and obtain the azelnidipine compositions under 50Pa.
Embodiment 2
The azelnidipine preparation of compositions
Azelnidipine 8g, ethyl acetate 65ml after the stirring and dissolving, adds beta-schardinger dextrin-56g, is stirred to pasty state, removes ethyl acetate and obtain the azelnidipine compositions under 50Pa.
Embodiment 3
The azelnidipine preparation of compositions
Azelnidipine 8g, ethyl acetate 100ml after the stirring and dissolving, adds beta-schardinger dextrin-120g, is stirred to pasty state, removes ethyl acetate and obtain the azelnidipine compositions under 50Pa.
Embodiment 4
Azelnidipine compositions 48g
Microcrystalline Cellulose 30g
Starch 20g
Low-substituted hydroxypropyl cellulose 10g
Magnesium stearate 1.1g
Get the recipe quantity azelnidipine, mix with pharmaceutic adjuvants such as microcrystalline Cellulose, starch, cross 100 mesh sieves repeatedly, make mix homogeneously, to contain 8% polyvinylpyrrolidone ethanol liquid in right amount is binding agent system soft material, and 24 mesh sieves are granulated excessively, and wet granular is dry back with 24 mesh sieve granulate in about 60 ℃, add the magnesium stearate mixing of 1% amount, tabletting obtains the azelnidipine tablet.
Embodiment 5
Azelnidipine compositions 48g
Microcrystalline Cellulose 30g
Starch 20g
Low-substituted hydroxypropyl cellulose 10g
Get the recipe quantity azelnidipine, mix with pharmaceutic adjuvants such as microcrystalline Cellulose, starch, cross 100 mesh sieves repeatedly, make mix homogeneously, to contain 8% polyvinylpyrrolidone ethanol liquid in right amount is binding agent system soft material, cross 24 mesh sieves and granulate, wet granular in about 60 ℃ dry back with sieving granulate in 24 months, fill gets the azelnidipine capsule in capsule.
Rat pharmacokinetics comparative experiments example
Get the SD male rat of body weight 150-180g, intravenous injection azelnidipine 1mg/kg (uses the 0.1mol/L dissolving with hydrochloric acid respectively, the sodium chloride injection dilution), irritate stomach azelnidipine 1mg/kg (5%CMCNa suspendible) and azelnidipine compositions 1mg/kg (in azelnidipine, the 5%CMCNa suspendible), measure blood plasma azelnidipine concentration.The result shows that the bioavailability of azelnidipine compositions is 42.2%, compares with the bioavailability 22.1% of azelnidipine, and the azelnidipine compositions can significantly improve the bioavailability of azelnidipine.
Table 1: rat pharmacokinetic parameter (in azelnidipine vein or oral 1mg/kg)
Conventional azelnidipine sheet prepares reference example
Azelnidipine 8g
Mannitol 30g
Microcrystalline Cellulose 40g
Starch 20g
Low-substituted hydroxypropyl cellulose 10g
Tween 80 0.5g
Magnesium stearate 1.1g
Get the recipe quantity azelnidipine, mix with pharmaceutic adjuvants such as mannitol, microcrystalline Cellulose, starch, cross 100 mesh sieves repeatedly, make mix homogeneously, to contain 8% polyvinylpyrrolidone ethanol liquid in right amount is binding agent system soft material, and 24 mesh sieves are granulated excessively, and wet granular is dry back with 24 mesh sieve granulate in about 60 ℃, add the magnesium stearate mixing of 1% amount, tabletting obtains the azelnidipine tablet.
Claims (3)
1. azelnidipine compositions, it is characterized in that: described azelnidipine compositions makes with following method: azelnidipine 8g, ethyl acetate 50ml, after the stirring and dissolving, add beta-schardinger dextrin-40g, be stirred to pasty state, under 50Pa, remove ethyl acetate and obtain the azelnidipine compositions.
2. azelnidipine compositions, it is characterized in that: described azelnidipine compositions makes with following method: azelnidipine 8g, ethyl acetate 65ml, after the stirring and dissolving, add beta-schardinger dextrin-56g, be stirred to pasty state, under 50Pa, remove ethyl acetate and obtain the azelnidipine compositions.
3. azelnidipine compositions, it is characterized in that: described azelnidipine compositions makes with following method: azelnidipine 8g, ethyl acetate 100ml, after the stirring and dissolving, add beta-schardinger dextrin-120g, be stirred to pasty state, under 50Pa, remove ethyl acetate and obtain the azelnidipine compositions.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101597669A CN101401942B (en) | 2008-11-13 | 2008-11-13 | Azelnidipine composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101597669A CN101401942B (en) | 2008-11-13 | 2008-11-13 | Azelnidipine composition |
Publications (2)
| Publication Number | Publication Date |
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| CN101401942A CN101401942A (en) | 2009-04-08 |
| CN101401942B true CN101401942B (en) | 2011-03-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2008101597669A Active CN101401942B (en) | 2008-11-13 | 2008-11-13 | Azelnidipine composition |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101829067A (en) * | 2010-03-30 | 2010-09-15 | 北京华禧联合科技发展有限公司 | Azelnidipine osmotic pump controlled-release tablet and preparation method thereof |
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