CN101669948A - Sustained release tablets of nicotinic acid and lovatatin and preparation method thereof - Google Patents
Sustained release tablets of nicotinic acid and lovatatin and preparation method thereof Download PDFInfo
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- CN101669948A CN101669948A CN200810119826A CN200810119826A CN101669948A CN 101669948 A CN101669948 A CN 101669948A CN 200810119826 A CN200810119826 A CN 200810119826A CN 200810119826 A CN200810119826 A CN 200810119826A CN 101669948 A CN101669948 A CN 101669948A
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Abstract
The invention relates to a compound sustained release preparation taking nicotinic acid and lovatatin as active components, which comprises a release system and is characterized in that: the release system consists of a tablet core capable of making medicaments released slowly and a coating, wherein partial active components exist in the tablet core; and residual active components exist in the coating. The compound sustained release preparation has the characteristics of convenient administration, durable effect, stable treatment effect, small toxic and side effect and the like.
Description
Technical field
It is the compound slow release preparation of active component with nicotinic acid, lovastatin that the present invention relates to a kind of, it comprises a kind of delivery system, it is characterized in that: described delivery system is made up of label and coating that drug slow is discharged, a described active component part is present in the label, and the residual activity composition is present in the coating.Belong to field of medicaments
Background technology
Nicotinic acid is vitamin B group, mainly influences cholesterol and triglyceride metabolism, and oral more heavy dose of nicotinic acid can reduce VLDL and triglyceride levels (TG) in the blood, and long-term prescription also can reduce LDL and cholesterol levels; Lovastatin is the inhibitor of isolating a kind of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase from the aspergillus terreus fermentation liquid, medicine for the novel therapeutic hypercholesterolemia, it is a kind of nonactive prodrug, after the oral absorption, being hydrolyzed to activated product β-hydroxy acid and suppressing the HMG-CoA reductase liver, is 3-hydroxyl-3-first glutaryl coenzyme A (HMG-CoA) reductase inhibitor.
Nicotinic acid can reduce plasma triglyceride and VLDL, rising blood plasma HDL
2Apolipoprotein and HDL
2/ HDL
1Ratio.Confirm that recently nicotinic acid is for being lipoprotein LP reduction medicine.Nicotinic acid can reduce VLDL synthesizing in liver, reduces LDL then and generates.The reduction of VLDL may to reduce in the fatty tissue cAMP content relevant with nicotinic acid.CAMP reduces reduces the triglyceride enzymatic activity that relies on cAMP, and fatty tissue is decomposed minimizing, and the free fatty that is released in the blood reduces, and the synthetic triglyceride of liver reduces then; Nicotinic acid also can promote cholesterol through bile excretion, and hinders the esterification of cholesterol.Nicotinic acid can appropriateness improve the HDL level, thereby the effect of atherosclerosis and coronary heart disease is arranged.The effect of its rising HDL may with apo-A
ISynthetic relevant.
Lovastatin is the specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and this enzyme catalysis HMG-CoA is transformed into mevalonic acid.The HMG-CoA reductase is a rate-limiting enzyme in the cholesterol biosynthetic process.Lovastatin plays a role through being hydrolyzed into active β hydroxy acid form as nonactive prodrug.The mechanism of action that lovastatin reduces LDL may be because can competitive combine with HMG-CoA, and the activity of inhibitory enzyme makes synthetic minimizing of the interior CH of hepatocyte, thereby inducing hepatocyte film ldl receptor increases, then by the ldl receptor regulatory pathway, quicken the removing of LDL, blood plasma LDL-C level is descended
[4]
At present, nicotinic acid and lovastatin are clinical antiatherosclerotic commonly used, and the two drug combination has complementary action, can enlarge the crowd's of being suitable for scope.
Because T-CHOL (TC) is synthetic in the human body, is daily rhythmicity, synthetic the most vigorous between midnight to early morning, in order to ensure enough blood drug level is arranged in the human body between midnight to early morning, development day clothes slow release formulation once is very necessary.Therefore developing Lovastatin nicotinic acid slow-release tablets has obvious social and economic benefit.
Beneficial effect
1, nicotinic acid is different with the lovastatin mechanism of action, when the blood fat reducing level characteristics is arranged respectively, has stronger complementarity, and blood lipid level is improved comprehensively.
2, make slow releasing preparation, increase curative effect of medication and reduce medicine the gastrointestinal side effect.
3, pharmaceutical release time is obviously prolonged, therefore reduced medicining times, improve patient compliance, abirritate and untoward reaction.
Summary of the invention
The present invention relates to a kind of is the compound slow release preparation of active component with nicotinic acid, lovastatin, it comprises a kind of delivery system, it is characterized in that: described delivery system is made up of label and coating that drug slow is discharged, a described active component part is present in the label, and the residual activity composition is present in the coating.
Compound slow release preparation of the present invention is characterized in that: nicotinic acid, lovastatin all are slow release and discharge.
Compound slow release preparation of the present invention is characterized in that: the effective dose 100-3000mg of nicotinic acid, 500-2000mg; The effective dose of lovastatin is 10-100mg, preferred 20-50mg.
Compound slow release preparation of the present invention, it is characterized in that: described label is made up of in principal agent, slow-release material, filler, adhesive, lubricant, emulsifying agent, the wetting agent one or more, and described coating is made up of in principal agent, slow-release material, filler, emulsifying agent, wetting agent, the coating material one or more.
Compound slow release preparation of the present invention is characterized in that described slow-release material can select for use in hydroxypropyl methylcellulose, Sulisi aqueous dispersion, ethyl cellulose, methylcellulose, cellulose acetate-phthalate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, glyceryl monostearate, the hydroxy methocel one or more to make.
Compound slow release preparation of the present invention is characterized in that described filler can be selected from one or more in microcrystalline Cellulose, mannitol, low-substituted hydroxypropyl cellulose, polyvinyl alcohol, poly-phthalic acid vinyl acetate, Polyethylene Glycol, sodium alginate, chitosan, sucrose, lactose, starch, dextrin, Icing Sugar, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, the titanium dioxide.
Compound slow release preparation of the present invention is characterized in that described binding agent can be selected from one or more in water, ethanol, dehydrated alcohol, starch slurry, polyvidone, copolyvidone, crospolyvinylpyrrolidone, hydroxypropyl methylcellulose and/or other cellulose families.
Compound slow release preparation of the present invention is characterized in that described lubricant can select magnesium stearate, micropowder silica gel, Pulvis Talci, stearic acid, hydrogenated vegetable oil, polyethylene glycols for use, month hang in the pure magnesium sulfate one or more.
Compound slow release preparation of the present invention is characterized in that described emulsifying agent is selected from heal in acid glyceride, the fatty acid cane sugar ester one or more of polyoxyethylene sorbitan ester, glyceryl monostearate, poloxamer, mountain.
Compound slow release preparation of the present invention is characterized in that in the optional water of described wetting agent, ethanol, dehydrated alcohol, chloroform, acetone, the benzene one or more.
Compound slow release preparation of the present invention is characterized in that described coating material can be selected from one or more in hydroxypropyl methylcellulose, ethyl cellulose, starch, methylcellulose, cellulose acetate, cellulose diacetate, Triafol T, acrylic resin, Opadry, the Sulisi.
Slow releasing preparation of the present invention is characterized in that counting by weight percentage, and it consists of:
Label and/or ball core:
Principal agent 20～80%
Slow-release material 0～40%
Binding agent 0～10%
Lubricant 0～10%
Wetting agent 0～30%
Coating:
Principal agent 0～20%
Slow-release material 0～30%
Filler 0～2%
Emulsifying agent 0～2%
Wetting agent 20～80%
Coating material 0～10%
Compound slow release preparation of the present invention is characterized in that described compound slow release preparation comprises to be prepared as follows step:
(1) label preparation:
(1.1) take by weighing recipe quantity nicotinic acid and pulverized 80 mesh sieves, with principal agent and slow-release material mixing, standby;
(1.2) binding agent that takes by weighing recipe quantity is mixed with mixed solution with the wetting agent of recipe quantity, carries out wet granulation with mixed solution, and wet granular is crossed 20 mesh sieves and carried out granulate, and with 50 ℃ of oven dry, dried granule is crossed 16 mesh sieve granulate, and is standby;
(1.3) in (1.2) preparation granule, add lubricant according to the prescription ratio, mixing, tabletting promptly gets label.
(2) coating:
(2.1) lovastatin medicinal liquid coating:
(2.1.1) under stirring, with in the slow-release material of recipe quantity, the wetting agent that filler joins recipe quantity, to wait to be uniformly dispersed successively, placement is spent the night;
(2.1.2) the recipe quantity emulsifying agent is dissolved in the wetting agent of recipe quantity, standby;
(2.1.3) lovastatin with recipe quantity grinds well with the solution that (2.1.2) makes, and in the dispersion liquid that adding (2.1.2) makes under stirring, is uniformly dispersed, and (1.3) is made label carry out coating, promptly.
(2.2) to wetting agent, the coating tablets that (2.1.3) made promptly with the coating material homodisperse of recipe quantity for film coating.
Slow releasing preparation of the present invention is characterized in that, described slow releasing preparation nicotinic acid release characteristic is 1 hour: 5%～25%, 3 hours: 25%～45%, 6 hours: 45%～70%, 12 hours: more than 75%; The stripping of described slow releasing preparation lovastatin is characterized as 45 minutes: more than 75%.
Specific embodiment
Embodiment 1
The label prescription:
Nicotinic acid 500g
Hydroxypropyl emthylcellulose (HPMC K15M CR) 200g
Stearic acid 25g
Pulvis Talci 4g
Magnesium stearate 4g
PVP
K-30 20g
Water 100g
Ethanol 100g
Make 100
Lovastatin coating prescription:
Lovastatin 20g
Hydroxypropyl emthylcellulose (HPMC E5) 200g
PEG4000 5g
Poloxamer 2g
Water 250g
Ethanol 250g
Make 1000
The film coating prescription:
Opadry (03B6II94) 36g
Water 300g
Ethanol 300g
Make film coating liquid
Preparation method
(1) label preparation:
(1.1) take by weighing recipe quantity nicotinic acid and pulverized 80 mesh sieves, with nicotinic acid and hydroxypropyl emthylcellulose (HPMC K15M CR) mixing, standby;
(1.2) take by weighing the PVP of recipe quantity
K-30Pure water with recipe quantity is mixed with mixed solution, carries out wet granulation with mixed solution, and wet granular is crossed 20 mesh sieves and carried out granulate, and with 50 ℃ of oven dry, dried granule is crossed 16 mesh sieve granulate, and is standby;
(1.3) in (1.2) preparation granule, add stearic acid, Pulvis Talci, magnesium stearate according to the prescription ratio, mixing, tabletting promptly gets label.
(2) coating:
(2.1) lovastatin medicinal liquid coating:
(2.1.1) under stirring, hydroxypropyl emthylcellulose (HPMC E5), the PEG4000 with recipe quantity joins in the water of recipe quantity successively, waits to be uniformly dispersed, and placement is spent the night;
(2.1.2) the recipe quantity poloxamer is dissolved in the ethanol of recipe quantity, standby;
(2.1.3) lovastatin with recipe quantity grinds well with the molten alcoholic solution of poloxamer that (2.1.2) makes, and in the dispersion liquid that adding (2.1.2) makes under stirring, is uniformly dispersed, and (1.3) is made label carry out coating, promptly.
(2.2) to alcohol-water solution, the coating tablets that (2.1.3) made promptly with Opadry (03B6II94) homodisperse of recipe quantity for film coating.
Embodiment 2
The label prescription:
Nicotinic acid 750g
Hydroxypropyl emthylcellulose (HPMC K15M CR) 210g
Stearic acid 50g
Pulvis Talci 10g
Magnesium stearate 5g
PVP
K-30 29g
Water 145g
Ethanol 145g
Make 1000
Lovastatin coating prescription:
Lovastatin 20g
Hydroxypropyl emthylcellulose (HPMC E5) 200g
PEG4000 5g
Poloxamer 2g
Water 250g
Ethanol 250g
Make 1000
The film coating prescription:
Opadry (03B6II94) 36g
Water 300g
Ethanol 300g
Make film coating liquid
Preparation method is with embodiment 1.
Embodiment 3
The label prescription:
Nicotinic acid 1000g
Hydroxypropyl emthylcellulose (HPMC K15M CR) 195g
Stearic acid 40g
Pulvis Talci 6g
Magnesium stearate 6g
PVP
K-30 35g
Water 175g
Ethanol 175g
Make 1000
Lovastatin coating prescription:
Lovastatin 20g
Hydroxypropyl emthylcellulose (HPMC E5) 200g
PEG4000 5g
Poloxamer 2g
Water 250g
Ethanol 250g
Make 1000
The film coating prescription:
Opadry (03B6II94) 36g
Water 300g
Ethanol 300g
Make film coating liquid
Preparation method is with embodiment 1.
The slow releasing preparation of three embodiment preparations, nicotinic acid release characteristic and lovastatin stripping feature are as follows, and be all up to specification.
Nicotinic acid drug release determination result
Lovastatin dissolution determination result
Claims (8)
1, a kind of is the compound slow release preparation of active component with nicotinic acid, lovastatin, it comprises a kind of delivery system, it is characterized in that: described delivery system is made up of label and coating that drug slow is discharged, a described active component part be present in label and in, the residual activity composition is present in the coating.
2, compound slow release preparation according to claim 1 is characterized in that: nicotinic acid, lovastatin all are slow release and discharge.
3, compound slow release preparation according to claim 1 is characterized in that: the effective dose 100-3000mg of nicotinic acid, 500-2000mg; The effective dose of lovastatin is 10-100mg, preferred 20-50mg.
4, compound slow release preparation according to claim 1, it is characterized in that: described label and/or ball core are made up of in principal agent, slow-release material, filler, adhesive, lubricant, emulsifying agent, the wetting agent one or more, and described coating is made up of in principal agent, slow-release material, filler, emulsifying agent, wetting agent, the coating material one or more.
5, compound slow release preparation according to claim 4 is characterized in that:
Described slow-release material can select for use in hydroxypropyl methylcellulose, Sulisi aqueous dispersion, ethyl cellulose, methylcellulose, cellulose acetate-phthalate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, glyceryl monostearate, the hydroxy methocel one or more to make.
Described filler can be selected from one or more in microcrystalline Cellulose, mannitol, low-substituted hydroxypropyl cellulose, polyvinyl alcohol, poly-phthalic acid vinyl acetate, Polyethylene Glycol, sodium alginate, chitosan, sucrose, lactose, starch, dextrin, Icing Sugar, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, the titanium dioxide.
Described binding agent can be selected from one or more in water, ethanol, dehydrated alcohol, starch slurry, polyvidone, copolyvidone, crospolyvinylpyrrolidone, hydroxypropyl methylcellulose and/or other cellulose families.
Described lubricant can be selected one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, stearic acid, hydrogenated vegetable oil, polyethylene glycols, month pure magnesium sulfate of extension for use.
Described emulsifying agent is selected from heal in acid glyceride, the fatty acid cane sugar ester one or more of polyoxyethylene sorbitan ester, glyceryl monostearate, poloxamer, mountain.
In the optional water of described wetting agent, ethanol, dehydrated alcohol, chloroform, acetone, the benzene one or more.
Described coating material can be selected from one or more in hydroxypropyl methylcellulose, ethyl cellulose, starch, methylcellulose, cellulose acetate, cellulose diacetate, Triafol T, acrylic resin, Opadry, the Sulisi.
6, aforesaid right requires the slow releasing preparation described in the 1-5, it is characterized in that counting by weight percentage, and it consists of:
Label and/or ball core:
Principal agent 20～80%
Slow-release material 0～40%
Binding agent 0～10%
Lubricant 0～10%
Wetting agent 0～30%
Coating:
Principal agent 0～20%
Slow-release material 0～30%
Filler 0～2%
Emulsifying agent 0～2%
Wetting agent 20～80%
Coating material 0～10%
7,, it is characterized in that described compound slow release preparation comprises to be prepared as follows step according to the described compound slow release preparation of claim 1-6:
(1) label preparation:
(1.1) take by weighing recipe quantity nicotinic acid and pulverized 80 mesh sieves, with principal agent and slow-release material mixing, standby;
(1.2) binding agent that takes by weighing recipe quantity is mixed with mixed solution with the wetting agent of recipe quantity, carries out wet granulation with mixed solution, and wet granular is crossed 20 mesh sieves and carried out granulate, and with 50 ℃ of oven dry, dried granule is crossed 16 mesh sieve granulate, and is standby;
(1.3) in (1.2) preparation granule, add lubricant according to the prescription ratio, mixing, tabletting promptly gets label.
(2) coating:
(2.1) lovastatin medicinal liquid coating:
(2.1.1) under stirring, with in the slow-release material of recipe quantity, the wetting agent that filler joins recipe quantity, to wait to be uniformly dispersed successively, placement is spent the night;
(2.1.2) the recipe quantity emulsifying agent is dissolved in the wetting agent of recipe quantity, standby;
(2.1.3) lovastatin with recipe quantity grinds well with the solution that (2.1.2) makes, and in the dispersion liquid that adding (2.1.2) makes under stirring, is uniformly dispersed, and (1.3) is made label carry out coating, promptly.
(2.2) to wetting agent, the coating tablets that (2.1.3) made promptly with the coating material homodisperse of recipe quantity for film coating.
8, the described slow releasing preparation of claim 1-7 is characterized in that:
Described slow releasing preparation nicotinic acid release characteristic is 1 hour: 5%～25%, 3 hours: 25%～45%, 6 hours: 45%～70%, 12 hours: more than 75%.
The stripping of described slow releasing preparation lovastatin is characterized as 45 minutes: more than 75%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810119826A CN101669948A (en) | 2008-09-11 | 2008-09-11 | Sustained release tablets of nicotinic acid and lovatatin and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810119826A CN101669948A (en) | 2008-09-11 | 2008-09-11 | Sustained release tablets of nicotinic acid and lovatatin and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101669948A true CN101669948A (en) | 2010-03-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810119826A Pending CN101669948A (en) | 2008-09-11 | 2008-09-11 | Sustained release tablets of nicotinic acid and lovatatin and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675621A (en) * | 2012-05-30 | 2012-09-19 | 西北大学 | Poloxamer-niacin prodrug and preparation method thereof |
| CN103230368A (en) * | 2012-12-24 | 2013-08-07 | 山东新华制药股份有限公司 | Statin medicine preparation method |
| CN111971030A (en) * | 2018-02-16 | 2020-11-20 | 艾斯柏伦治疗公司 | Sustained release preparation of bipeda acid |
-
2008
- 2008-09-11 CN CN200810119826A patent/CN101669948A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675621A (en) * | 2012-05-30 | 2012-09-19 | 西北大学 | Poloxamer-niacin prodrug and preparation method thereof |
| CN102675621B (en) * | 2012-05-30 | 2014-03-26 | 西北大学 | Poloxamer-niacin prodrug and preparation method thereof |
| CN103230368A (en) * | 2012-12-24 | 2013-08-07 | 山东新华制药股份有限公司 | Statin medicine preparation method |
| CN111971030A (en) * | 2018-02-16 | 2020-11-20 | 艾斯柏伦治疗公司 | Sustained release preparation of bipeda acid |
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Open date: 20100317 |