CN1395928A - Slow-releasing acipimox tablet - Google Patents
Slow-releasing acipimox tablet Download PDFInfo
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- CN1395928A CN1395928A CN02129444.5A CN02129444A CN1395928A CN 1395928 A CN1395928 A CN 1395928A CN 02129444 A CN02129444 A CN 02129444A CN 1395928 A CN1395928 A CN 1395928A
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Abstract
A slow-releasing acipimox tablet for regulating blood fat is prepared from acipimox, slow-releasing agent, adhesive and lubricant through proportioning, wet granulating, baking, mixing with lubricant, and tabletting. Its advantages are stable concentration of medicine in blood, durable acting and low toxic by-effect.
Description
Affiliated technical field
The invention belongs to medical technology, particularly a kind of slow-releasing acipimox tablet, it is efficient, safe blood lipid regulation medicine.
Background technology
In recent years, along with dietary habit change, living standard raising, operating pressure increase, hyperlipemia and hyperproteinemia patient are more and more, and patient group is rejuvenation more and more.Hyperlipemia and hyperproteinemia are one group of clinical common lipid metabolic disorder diseases, be called hyperlipemia (Hyperlipemia) in limited time when the concentration of blood plasma lipide surpasses the normal value height, lipoprotein surpasses the normal value height and is called hyperlipoproteinemia (Hyperlipoproteinemia) in limited time in the blood plasma.Epidemiological study shows that increasing of blood plasma low density lipoprotein, LDL (LDL) and very low density lipoprotein (VLDL) (VLDL) level is the key factor of early starting pulse atherosclerosis and coronary heart disease.Statistical analysis shows, the every reduction by 1% of serum cholesterol, and the pathogenetic risk of coronary disease will reduce by 2%.Therefore, logical diet, motion and Drug therapy are very important to hyperlipemia and hyperlipoproteinemia patient.
Blood lipid regulation medicine commonly used at present has: cholic acid chelating agent, as colestyramine, colestipol etc.; Statins is as lovastatin, simvastatin, atorvastatin etc.; The special class of shellfish is as clofibrate; The nicotinic acid class is as nicotinic acid.
Nicotinic acid has tangible blood lipid regulation effect.Main mechanism is synthetic for lipoprotein in the inhibition liver, suppresses the synthetic of VLDL and LDL, increases blood plasma HDL level.But clinical safety in utilization is relatively poor, except that feel sick, the stomachache, flushing, skin pruritus, but also affecting glucose and uric acid metabolism approach increase the weight of the state of an illness of diabetes and patient with gout.The clinical hyperlipemia that can be used for any kind except that homozygote familial hypercholesterolemia and I type hyperlipoproteinemia.
Acipimox is a nicotinic acid derivates, this medicine mainly acts on fatty tissue, discharges free fatty (FFA) by suppressing fatty tissue, reduces the synthetic of LDL and VLDL, thereby the level of VLDL and LDL in the reduction blood plasma is simultaneously by suppressing the active blood plasma HDL level that increases of hepatic lipase.This product is compared with nicotinic acid, have the following advantages (Clin.Pharmacol.Ther., Vol 28,790-795,1980; Diabetic Med., Vol 9,908-914,1992; J.Intern.Med., Vol 230,415-421,1991):
1, lipotropism is separated the strong this product lipotropism of effect and is separated 20 times that act as nicotinic acid, and the effect that reduces plasma F FA and TG is respectively 3.3 times and 6.5 times of naotin, and the FFA rebound phenomenon significantly is lower than the latter.
2, long half time is different with nicotinic acid, and this product oral administration post-absorption is rapid, complete, no first pass metabolism, and the half-life is longer than nicotinic acid, and effect for reducing blood fat can be kept the long period.
3, the scope of application is wide, and this product evident in efficacy can be used for treating II
A, II
B, III, IV and V-type hyperlipoproteinemia.According to interrelated data statistics, type 2 diabetes mellitus more than 50 years old (NIDDM) patient glucose tolerance descends, and increases the weight of the diabetics state of an illness and forbids.This product can significantly be improved patient's glucose tolerance, and does not have interaction with oral antidiabetic drug, is particularly useful for diabetics.In addition because this product does not influence blood uric acid metabolism, clinically also can be used for the hyperuricemia patient.
4, consumption is little, and the taking convenience patient takes this product 375mg at every turn, can obtain satisfied effect for reducing blood fat every day for 2 times.The consumption per day of nicotinic acid is 3g, is equivalent to 4～6 times of acipimox consumption.
5, the little clinical trial of side effect shows, acipimox is to the hyperlipidemia patient better tolerance, and the incidence rate of flushing, pruritus, gastrointestinal function imbalance significantly is lower than nicotinic acid, and patient's liver enzyme activity and blood uric acid all do not made significant difference, good patient compliance more is applicable to long-term prescription.
Acipimox is developed by Italian Farmitalia Carlo Erba company, and the patent No. is US4, and 002,750 (1977).The acipimox capsule is developed by Italian Farmitalia Carlo Erba company, in 1985 in Italy's listing, specification is 250mg, indication is IIA, IIB, III, IV and V-type hyperlipoproteinemia, consumption is a 250mg, 2～3 times on the one.
Summary of the invention
The object of the invention provides a kind of slow-releasing acipimox tablet, and it is efficient, safe blood lipid regulation medicine, slowly discharges and keeps comparatively stable blood concentration and longer action time, has toxic and side effects and reduces, takes convenient advantage.
Weight of the present invention is formed and is comprised:
100 parts of acipimoxs
1.5 parts～50 parts of slow releasing agents
30 parts～60 parts of binding agents
1 part of lubricant
Above-mentioned slow releasing agent is meant hydroxypropyl methylcellulose (HPMC)-4M, HPMC-15M, HPMC-100M, polyvinylpyrrolidone (PVP), ethyl cellulose (EC), methylcellulose (MC), hydroxyethyl-cellulose (HEC), hexadecanol, octadecanol, Rikemal B 200 (Compritol 888 ATO), stearic acid, monostearate, glyceride, Brazil wax, sodium carboxymethyl cellulose (CMC-Na), polyvinyl alcohol (PVA), one of chitin chitin or they optional two or more.
Above-mentioned binding agent is meant that concentration is PVP ethanol solution, PVP alcoholic solution, PVP aqueous solution, EC ethanol solution, EC alcoholic solution, EC acetone soln or the HPMC aqueous solution of 1%--20%.
Above-mentioned lubricant is a magnesium stearate.
Preparation technology of the present invention adds the binding agent granulation with the acipimox of recipe quantity and slow releasing agent mix homogeneously, and 40 ℃-80 ℃ are dry down, put in order dried granule, add the lubricant of recipe quantity in dried granule, mixing, and special-shaped stamping gets final product.
Slow-releasing acipimox tablet of the present invention is taken twice every day, each a slice, compare with the acipimox capsule, because the characteristics that this dosage form slowly discharges, can continue release in 8 hours, thereby keep comparatively stable blood concentration and longer action time, have toxic and side effects and reduce, take convenient advantage.Therefore, develop this product and will obtain social benefit and economic benefit widely.
Description of drawings
Fig. 1: the cumulative in vitro release profiles of prescription A; Fig. 2: the cumulative in vitro release profiles of prescription B; Fig. 3: the cumulative in vitro release profiles of prescription C; Fig. 4: the cumulative in vitro release profiles of prescription D; Fig. 5: the cumulative in vitro release profiles of prescription E; Fig. 6: the cumulative in vitro release profiles of prescription F; Fig. 7: the cumulative in vitro release profiles of prescription G; Fig. 8: the cumulative in vitro release profiles of prescription H.
The specific embodiment
Embodiment:
Select eight kinds of concrete prescriptions as follows:
Prescription A: acipimox 375g
HPMC-4M????????????????????????????15g
8%PVP ethanol solution 150g
Magnesium stearate 2g
Preparation technology: acipimox is crossed 100 mesh sieves, HPMC-4M crosses 80 mesh sieves, take by weighing the acipimox and the HPMC-4M mix homogeneously of recipe quantity, add the 8%PVP ethanol solution and granulate in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, the magnesium stearate that adds recipe quantity in the dried granule, mixing, special-shaped stamping promptly get about 850 of slice, thin piece.
Prescription B: acipimox 375g
HPMC-4M????????????????????????????80g
8%PVP ethanol solution 150g
Magnesium stearate 2g
Preparation technology is with prescription A.
Prescription C: acipimox 375g
HPMC-15M???????????????????????????15g
8%PVP ethanol solution 150g
Magnesium stearate 2g
Preparation technology is with prescription A.
Prescription D: acipimox 375g
HPMC-15M???????????????????????????80g
8%PVP ethanol solution 150g
Magnesium stearate 2g
Preparation technology is with prescription A.
Prescription E: acipimox 375g
EC?????????????????????????????????10g
5%PVP ethanol solution 120g
Magnesium stearate 2g
Preparation technology is with prescription A.
Prescription F: acipimox 375g
EC??????????????????????????????????60g
5%EC ethanol solution 120g
Magnesium stearate 2g
Preparation technology is with prescription A.
Prescription G: acipimox 375g
Compritol?888?ATO????????????????????15g
8%PVP ethanol solution 150g
Magnesium stearate 2g
Preparation technology is with prescription A.
Prescription H: acipimox 375g
Compritol?888?ATO????????????????????100g
8%PVP ethanol solution 150g
Magnesium stearate 2g
Preparation technology is with prescription A.
Slow-releasing acipimox tablet (prescription A-H), its extracorporeal releasing experiment method is as follows: get this product according to drug release determination method (two appendix XD first methods of Chinese Pharmacopoeia version in 2000), utilize dissolution determination device (two appendix XC first methods of Chinese Pharmacopoeia version in 2000), 1000ml is a solvent with hydrochloric acid solution (9 → 1000), rotating speed 50 changes, in accordance with the law operation.Got solution 10ml (and instant replenish equivalent solvent) at 1,4 and 8 hour respectively, filter, precision is measured subsequent filtrate 2ml, put in the 100ml volumetric flask, with same solvent dilution to scale, as need testing solution; Other the acipimox reference substance that is dried to constant weight of learning from else's experience 105 ℃ is an amount of, accurate claim fixed, add hydrochloric acid solution (9 → 1000) dissolving and quantitatively dilution make the solution that contains 7.5 μ g among every 1ml, product solution in contrast.Respectively according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), measure the trap of need testing solution and reference substance solution at the wavelength place of 269nm, calculate according to external standard method, draw every burst size of this product and should be respectively more than 10%～30%, 40%～70% and 75% of labelled amount at 1,4,8 hour, all should be up to specification.See table 1-8 and accompanying drawing 1-8 for details.
Animal drug disposition dynamic metabolism experimental technique of the present invention is as follows: experiment is divided into two groups, every group of 6 Canis familiaris L.s; Matched group gives oral common acipimox capsule (250mg/ grain), every day three times, each 1; Experimental group gives oral the present invention (prescription A-H, 375mg/ sheet), every day twice, each a slice; Respectively in administration after 1,2,3,4,5,6,7 days, get the blood drug level of determination of serum acipimox, the result shows: matched group and experimental group all do not have marked difference at the area under the drug-time curve (AUC) of each time point, prompting the present invention is according to twice of every day, each 1 oral administration can reach ideal blood drug level, has excellent curative.
Table 1: prescription A cumulative in vitro release
| Time (hour) | 1 | ?2 | ?3 | ?4 | ?5 | ?6 | ?7 | ?8 |
| Release (%) | 28 | ?42 | ?55 | ?68 | ?78 | ?87 | ?91 | ?98 |
Table 2: prescription B cumulative in vitro release
| Time (hour) | 1 | ?2 | ?3 | ?4 | ?5 | ?6 | ?7 | ?8 |
| Release (%) | 14 | ?25 | ?35 | ?45 | ?55 | ?65 | ?74 | ?82 |
Table 3: prescription C cumulative in vitro release
| Time (hour) | 1 | ?2 | ?3 | ?4 | ?5 | ?6 | ?7 | ?8 |
| Release (%) | 26 | ?39 | ?51 | ?63 | ?74 | ?85 | ?90 | ?98 |
Table 4: prescription D cumulative in vitro release
| Time (hour) | 1 | ?2 | ?3 | ?4 | ?5 | ?6 | ?7 | ?8 |
| Release (%) | 12 | ?21 | ?31 | ?42 | ?50 | ?62 | ?72 | ?81 |
Table 5: prescription E cumulative in vitro release
| Time (hour) | 1 | ?2 | ?3 | ?4 | ?5 | ?6 | ?7 | ?8 |
| Release (%) | 27 | ?45 | ?55 | ?66 | ?72 | ?81 | ?90 | ?97 |
Table 6: prescription F cumulative in vitro release
| Time (hour) | 1 | ?2 | ?3 | ?4 | ?5 | ?6 | ?7 | ?8 |
| Release (%) | 10 | ?23 | ?37 | ?48 | ?55 | ?64 | ?75 | ?84 |
Table 7: prescription G cumulative in vitro release
| Time (hour) | 1 | ?2 | ?3 | ?4 | ?5 | ?6 | ?7 | ?8 |
| Release (%) | 28 | ?47 | ?57 | ?66 | ?76 | ?85 | ?92 | ?98 |
Table 8: prescription H cumulative in vitro release
| Time (hour) | 1 | ?2 | ?3 | ?4 | ?5 | ?6 | ?7 | ?8 |
| Release (%) | 12 | ?24 | ?37 | ?45 | 56 | ?63 | ?70 | ?82 |
Claims (6)
1, a kind of slow-releasing acipimox tablet is characterized in that the weight composition of this slow releasing tablet comprises:
100 parts of acipimoxs
1.5～50 parts of slow releasing agents
30～60 parts of binding agents
1 part of lubricant
Described slow releasing agent is meant hydroxypropyl methylcellulose (HPMC)-4M, HPMC-15M, HPMC-100M, polyvinylpyrrolidone (PVP), ethyl cellulose (EC), methylcellulose (MC), hydroxyethyl-cellulose (HEC), hexadecanol, octadecanol, Rikemal B 200 (Compritol 888 ATO), stearic acid, monostearate, glyceride, Brazil wax, sodium carboxymethyl cellulose (CMC-Na), polyvinyl alcohol (PVA), one of chitin chitin or they optional two or more;
Described binding agent is meant that concentration is PVP ethanol solution, PVP alcoholic solution, PVP aqueous solution, EC ethanol solution, EC alcoholic solution, EC acetone soln or the HPMC aqueous solution of 1%--20%;
Described lubricant is a magnesium stearate.
2, slow-releasing acipimox tablet according to claim 1 is characterized in that described weight composition comprises:
100 parts of acipimoxs
4～21.3 parts of HPMC-4M
40 parts of 8%PVP ethanol solutions
1 part of magnesium stearate.
3, slow-releasing acipimox tablet according to claim 1 is characterized in that described weight composition comprises:
100 parts of acipimoxs
4～21.3 parts of HPMC-15M
40 parts of 8%PVP ethanol solutions
1 part of magnesium stearate.
4, slow-releasing acipimox tablet according to claim 1 is characterized in that described weight composition comprises:
100 parts of acipimoxs
2.67～16 parts of EC
32 parts of 5%PVP ethanol solutions
1 part of magnesium stearate.
5, slow-releasing acipimox tablet according to claim 1 is characterized in that described weight composition comprises:
100 parts of acipimoxs
4～26.7 parts of Rikemal B 200s
40 parts of 8%PVP ethanol solutions
1 part of magnesium stearate.
6, the preparation technology of the described slow-releasing acipimox tablet of claim 1, it is characterized in that it is through following step: the acipimox and the slow releasing agent mix homogeneously of recipe quantity are added the binding agent granulation, 40 ℃-80 ℃ dry down, whole dried granule, the lubricant that in dried granule, adds recipe quantity, mixing, special-shaped stamping gets final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN02129444.5A CN1209109C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing acipimox tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN02129444.5A CN1209109C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing acipimox tablet |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1395928A true CN1395928A (en) | 2003-02-12 |
| CN1209109C CN1209109C (en) | 2005-07-06 |
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ID=4746247
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN02129444.5A Expired - Lifetime CN1209109C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing acipimox tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1209109C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101791300A (en) * | 2010-03-23 | 2010-08-04 | 沈阳药科大学 | Acipimox push-pull osmotic pump controlled release tablet and preparation method thereof |
| CN104586810A (en) * | 2015-01-22 | 2015-05-06 | 山东新时代药业有限公司 | Acipimox sustained-release tablet and preparation method thereof |
-
2002
- 2002-08-26 CN CN02129444.5A patent/CN1209109C/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101791300A (en) * | 2010-03-23 | 2010-08-04 | 沈阳药科大学 | Acipimox push-pull osmotic pump controlled release tablet and preparation method thereof |
| CN101791300B (en) * | 2010-03-23 | 2013-05-29 | 沈阳药科大学 | Acipimox push-pull osmotic pump controlled release tablet and preparation method thereof |
| CN104586810A (en) * | 2015-01-22 | 2015-05-06 | 山东新时代药业有限公司 | Acipimox sustained-release tablet and preparation method thereof |
| CN104586810B (en) * | 2015-01-22 | 2017-06-30 | 山东新时代药业有限公司 | A kind of slow-releasing acipimox tablet and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN1209109C (en) | 2005-07-06 |
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Owner name: LUNAN PHARMACEUTICAL GROUP CO., LTD. Free format text: FORMER NAME OR ADDRESS: LUNAN PHARMACY CO. LTD. |
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Address after: 276005 No. 209 Hongqi Road, Shandong, Linyi Patentee after: LUNAN PHARMACEUTICAL Group Corp. Address before: 276003 No. 107, No. 1, Linxi, Shandong, Linyi Patentee before: Lunan Pharmaceutical Co.,Ltd. |
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Granted publication date: 20050706 |