CN101152187A - Eplerenone pharmaceutical composition - Google Patents
Eplerenone pharmaceutical composition Download PDFInfo
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- CN101152187A CN101152187A CNA2006101134672A CN200610113467A CN101152187A CN 101152187 A CN101152187 A CN 101152187A CN A2006101134672 A CNA2006101134672 A CN A2006101134672A CN 200610113467 A CN200610113467 A CN 200610113467A CN 101152187 A CN101152187 A CN 101152187A
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- China
- Prior art keywords
- eplerenone
- poloxamer
- pharmaceutical composition
- magnesium stearate
- microcrystalline cellulose
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Abstract
The invention discloses a drug combination containing eplerenone. The combination also contains nonionic surface active agent, has high bioavailability, and is used to treat cardiovascular diseases including hypertension.
Description
Technical field
The present invention relates to a kind of antihypertensive pharmaceutical composition, particularly a kind of pharmaceutical composition that contains eplerenone.
Background technology
Eplerenone is a kind of selectivity aldosterone inhibitor (SAB), the function of inhibitory hormone aldosterone specifically.Aldosterone is a kind of important composition in the renin angiotensin aldosterone system (RAAS), is bringing into play important effect when regulating the cardiovascular system of human body function, and its chemical structural formula is as follows:
Eplerenone can effectively be controlled hypertension, alleviates the infringement of target organs such as the heart, brain and kidney, improve type 2 diabetes mellitus patient Microalbuminuria, and its side effect incidence rate is similar to placebo, well-tolerated.Control hypertension, cardiovascular disease that prevention is relevant with target organ damage, improve hyperpietic's sides such as prognosis for the hyperpietic with all significant.
CN99814110 and US20030215518 disclose the micronization eplerenone pharmaceutical composition.EP1527782 public use micronization eplerenone is made tablet and capsule.Micronized pharmaceutical composition is though improved bioavailability in its external stripping and the body, this method complicated process of preparation, production cost height to a certain extent.
US2003236236 discloses by adding surfactant, comprise that Polysorbate, polyoxyethylene fatty acid ester, fatty acid Pyrusussuriensis are smooth, increase the method for insoluble drug, but openly be not to be used for eplerenone surfactant and consumption thereof specifically, also not openly when active component is eplerenone, the degree that its dissolution and bioavailability are improved.
Summary of the invention
The poorly water-soluble of eplerenone, oral bioavailability is low, and the present invention improves bioavailability of medicament by adding nonionic hydrophilic surfactant poloxamer, thereby improves the drug effect of eplerenone.
Pharmaceutical composition of the present invention contains the nonionic hydrophilic surfactant, can be selected from ethylene oxide/propylene oxide copolymer (poloxamer, poloxamers), comprise poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407.
Compositions of the present invention contains (weight) 5～30% eplerenones, 5～15% poloxamers, and in 55～90% the disintegrating agent, filler, binding agent, lubricant one or more.
For combination of oral medication, the dissolution rate of poorly water soluble drugs is the key factor that influences drug absorption.The present invention rationally selects disintegrating agent for use, accelerates disintegration rate, promotes the stripping of medicine, increases the absorption of medicine.
The available disintegrating agent of the present invention comprises one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, the microcrystalline Cellulose.
The available binding agent of the present invention comprises one or more in polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, sodium alginate, the aluminium-magnesium silicate.
The available filler of the present invention comprises one or more in lactose, sucrose, sorbitol, mannitol, pregelatinized Starch, the starch.
The available lubricant of the present invention comprises one or more in magnesium stearate, calcium stearate, stearic acid, Pulvis Talci, silicon dioxide, micropowder silica gel, Polyethylene Glycol, the Stepanol MG.
The invention provides a kind of eplerenone pharmaceutical composition, its disintegrate is rapid, by adding the nonionic hydrophilic surfactant, improves bioavailability height and blood drug level, improve the curative effect of eplerenone, and preparation method is simple, is fit to large-scale production.
The specific embodiment
Come eplerenone pharmaceutical composition of the present invention done further specifying by the following examples, but do not represent the embodiment limitation of the present invention.
Embodiment 1:
| Eplerenone | 10％ |
| Lactose | 22.5％ |
| Microcrystalline Cellulose | 25％ |
| Pregelatinized Starch | 15％ |
| Poloxamer 407 | 7％ |
| Carboxymethyl starch sodium | 20％ |
| Magnesium stearate | 0.5％ |
Preparation method: lactose, microcrystalline Cellulose, pregelatinized Starch, carboxymethyl starch sodium, magnesium stearate, the poloxamer 407 of getting recipe quantity are crossed 60 mesh sieves, mix homogeneously, get adjuvant with eplerenone equivalent, the method mix homogeneously that progressively increases with equivalent, direct powder compression promptly gets the eplerenone sheet.
Embodiment 2:
| Eplerenone | 15％ |
| Lactose | 29.5％ |
| Microcrystalline Cellulose | 25％ |
| Pregelatinized Starch | 20％ |
| Poloxamer 188 | 10％ |
| Water (or ethanol water) | In right amount |
| Magnesium stearate | 0.5％ |
Preparation method: earlier above-mentioned adjuvant pulverize separately is crossed 100 mesh sieves, with eplerenone, lactose, microcrystalline Cellulose, poloxamer 188, the abundant mix homogeneously of pregelatinized Starch, add suitable quantity of water (or ethanol water) and make soft material, oven dry after 30 mesh sieves are granulated, 24 mesh sieve granulate, add the magnesium stearate mix homogeneously, the control tablet weight, tabletting promptly gets the eplerenone sheet.
Embodiment 3:
| Eplerenone | 20％ |
| Mannitol | 29％ |
| Microcrystalline Cellulose | 30％ |
| Poloxamer 338 | 10％ |
| Low-substituted hydroxypropyl cellulose | 7％ |
| The polyvinylpyrrolidone aqueous solution | In right amount |
| Crospolyvinylpyrrolidone | 3％ |
| Magnesium stearate | 1％ |
Preparation method: earlier above-mentioned adjuvant pulverize separately is crossed 100 mesh sieves, with eplerenone, mannitol, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, poloxamer 338 abundant mix homogeneously, add an amount of polyvinylpyrrolidone aqueous solution and make soft material, oven dry after 20 mesh sieves are granulated, 20 mesh sieve granulate, add crospolyvinylpyrrolidone and magnesium stearate mixing, the control tablet weight, tabletting promptly gets the eplerenone sheet.This example is for adding in the disintegrating agent and add use in conjunction, in be microcrystalline Cellulose and low-substituted hydroxypropyl methylcellulose with disintegrating agent, adding disintegrating agent is crospolyvinylpyrrolidone.
Embodiment 4:
| Eplerenone | 40％ |
| Lactose | 27％ |
| Microcrystalline Cellulose | 20％ |
| Low-substituted hydroxypropyl cellulose | 7％ |
| Poloxamer 237 | 5％ |
| Water | In right amount |
| Magnesium stearate | 1％ |
Preparation method: earlier above-mentioned adjuvant pulverize separately is crossed 100 mesh sieves, with eplerenone, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, poloxamer 237, abundant mix homogeneously, add suitable quantity of water solution and make soft material, oven dry after 20 mesh sieves are granulated, 20 mesh sieve granulate, add the magnesium stearate mixing, the control tablet weight, tabletting promptly gets the eplerenone sheet.
Embodiment 5:
| Eplerenone | 10％ |
| Lactose | 29.5％ |
| Microcrystalline Cellulose | 25％ |
| Pregelatinized Starch | 15％ |
| Carboxymethyl starch sodium | 20％ |
| Magnesium stearate | 0.5％ |
Preparation method: the eplerenone of getting recipe quantity, cross 100 mesh sieves, other gets lactose, microcrystalline Cellulose, pregelatinized Starch, carboxymethyl starch sodium, the magnesium stearate of recipe quantity and crosses 60 mesh sieves, mix homogeneously, get adjuvant with eplerenone equivalent, cross 60 mesh sieve mix homogeneously with the method that equivalent is progressively increased, direct powder compression promptly gets the eplerenone sheet.
Embodiment 6: pharmacokinetics contrast experiment
Divide two groups at random to 10 human volunteers, first group of 5 volunteer takes the tablet that contains 7% poloxamer 407 of embodiment 1 preparation, and second group of 5 volunteer takes the tablet that does not contain poloxamer 407 of embodiment 5 (comparative example) preparation.
Taking back 0,1,2,3,4,6,8,10,12,16 and 20 hour difference blood sampling, and eplerenone is being detected the maximum plasma concentration (C of record medicine
Max, ng/ml) and blood drug level to the area under curve of time (AUC, ng.h/ml).
The C of embodiment 1 and embodiment 5 (comparative example)
MaxWith AUC value contrast table
| Take embodiment 1 | Take embodiment 5 (comparative example) | |
| C maxRatio | 9.1 | 1 |
| The ratio of AUC | 7.8 | 1 |
Last table result shows, adds non-ionic surface active agent poloxamer 407 in tablet, can significantly improve eplerenone in the intravital bioavailability of people.
Claims (8)
1. a pharmaceutical composition that contains eplerenone is characterized in that containing nonionic surfactant and other pharmaceutic adjuvant acceptable.
2. according to the Pharmaceutical composition of claim 2, it is characterized in that containing 5～30% (weight) eplerenone, the nonionic surfactant of 5-15% and pharmaceutic adjuvant acceptable of 55-90%.
3. according to the Pharmaceutical composition of claim 1 or 2, it is characterized in that described nonionic surfactant is a poloxamer.
4. according to the Pharmaceutical composition of claim 3, it is characterized in that described nonionic surfactant is selected from poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407.
5. according to the Pharmaceutical composition of claim 4, have following composition:
。
6. according to the Pharmaceutical composition of claim 4, have following composition:
。
7. according to the Pharmaceutical composition of claim 4, have following composition:
。
8. according to the Pharmaceutical composition of claim 4, have following composition:
。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101134672A CN101152187A (en) | 2006-09-29 | 2006-09-29 | Eplerenone pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101134672A CN101152187A (en) | 2006-09-29 | 2006-09-29 | Eplerenone pharmaceutical composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101152187A true CN101152187A (en) | 2008-04-02 |
Family
ID=39254207
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006101134672A Pending CN101152187A (en) | 2006-09-29 | 2006-09-29 | Eplerenone pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101152187A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105362242A (en) * | 2015-12-10 | 2016-03-02 | 合肥久诺医药科技有限公司 | Eplerenone dispersible tablet |
| CN107456445A (en) * | 2016-06-06 | 2017-12-12 | 南京卡文迪许生物工程技术有限公司 | Eplerenone oral solid formulation and preparation method thereof |
| CN113197941A (en) * | 2021-04-16 | 2021-08-03 | 一力制药股份有限公司 | Eplerenone pharmaceutical composition, and preparation method and application thereof |
-
2006
- 2006-09-29 CN CNA2006101134672A patent/CN101152187A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105362242A (en) * | 2015-12-10 | 2016-03-02 | 合肥久诺医药科技有限公司 | Eplerenone dispersible tablet |
| CN105362242B (en) * | 2015-12-10 | 2019-04-26 | 合肥久诺医药科技有限公司 | A kind of eplerenone dispersible tablet |
| CN107456445A (en) * | 2016-06-06 | 2017-12-12 | 南京卡文迪许生物工程技术有限公司 | Eplerenone oral solid formulation and preparation method thereof |
| CN113197941A (en) * | 2021-04-16 | 2021-08-03 | 一力制药股份有限公司 | Eplerenone pharmaceutical composition, and preparation method and application thereof |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20080402 |