CN1395927A - Slow-releasing acipimox capsule - Google Patents
Slow-releasing acipimox capsule Download PDFInfo
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- CN1395927A CN1395927A CN 02129443 CN02129443A CN1395927A CN 1395927 A CN1395927 A CN 1395927A CN 02129443 CN02129443 CN 02129443 CN 02129443 A CN02129443 A CN 02129443A CN 1395927 A CN1395927 A CN 1395927A
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Abstract
A slow-releasing acipimox capsule for regualting blood fat is prepared from acipimox, empty core, slow-releasing agent, plasticizer and antisticking agent through preparing medicine core, drying, then coating slow-releasing layer, drying by blowing and loading in capsule. 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 capsule, 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, the lipotropism effect of separating is strong, and this product lipotropism 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, different with nicotinic acid, this product oral administration post-absorption is rapid, complete, no first pass metabolism, 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 is evident in efficacy, and this product 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, taking convenience, and the 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, side effect is little, and clinical trial shows that acipimox is to the hyperlipidemia patient better tolerance, the incidence rate of flushing, pruritus, gastrointestinal function imbalance significantly is lower than nicotinic acid, and liver enzyme activity and blood uric acid to the patient all do not make significant difference, and 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 II
A, II
B, III, IV and V-type hyperlipoproteinemia, consumption is a 250mg, 2～3 times on the one.
Summary of the invention
The invention provides a kind of slow-releasing acipimox capsule, it is improvements over the prior art, can be used as efficient, safe blood lipid regulation medicine, slowly discharge and keep comparatively stable blood concentration and longer action time, have toxic and side effects and reduce, take convenient advantage.
Weight of the present invention is formed and is comprised:
100 parts of acipimoxs
158 parts of celphere
0.5～3.7 part of plasticizer
2.6～95 parts of slow-release materials
0～13 part of antiplastering aid
Above-mentioned slow releasing agent be meant ethyl cellulose (EC), stearic acid, cellulose acetate, Eudragit (acrylic resin) RS 100, Eudragit RL 100, Surelease (Aquacoat), Eudragit RS 30D, Eudragit RL 30D, one of Eudragit RS 30D, Eudragit NE 30D or they optional two or more.
The preparation of slow-releasing acipimox capsule divided for two steps, and the first step is that the raw material fine powder is adhered on the celphere by suitable adhesive, made to contain pill core, and second step was to containing pill core bag extended release coatings film, controlling principal agent and discharge.
Above-mentioned plasticizer is meant Polyethylene Glycol-6000, diethyl phthalate or triethyl citrate.
Above-mentioned antiplastering aid is meant Pulvis Talci.
Slow-releasing acipimox capsule of the present invention is taken twice every day, each one, 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: prescription A cumulative in vitro release profiles; Fig. 2: prescription B cumulative in vitro release profiles; Fig. 3: prescription C cumulative in vitro release profiles; Fig. 4: prescription D cumulative in vitro release profiles; Fig. 5: prescription E cumulative in vitro release profiles; Fig. 6: prescription F cumulative in vitro release profiles; Fig. 7: prescription G cumulative in vitro release profiles; Fig. 8: prescription H cumulative in vitro release profiles.
The specific embodiment
Embodiment:
(1) contains the preparation of pill core
Acipimox 190g
Celphere 300g
7%PVP solution (solvent is 90% ethanol) 200g preparation technology:
Acipimox is crossed 160 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, CYL 3bar, CAP1 0.8bar pours celphere into, pelletize.Blanking velocity 4rpm, the pump 12% of wriggling, rotary speed 145rpm, spray 7%PVP solution (solvent is 90% ethanol), 50 ℃ of oven dry.Pelletize finishes, discharging 500g.
(2) eight kinds of concrete prescriptions are as follows: (determining slow releasing agent kind and quantity) prescription A:
Contain pill core 500g
Ethyl cellulose 5g
Stearic acid 30g
Polyethylene Glycol-6000 1g
Pulvis Talci 4g
95% ethanol 400g preparation technology: recipe quantity takes by weighing and contains pill core, pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.6bar, CYL (inlet air air door pressure) 3bar, CAP1 (atomizing pressure) 0.9bar, rotary speed 170rpm, the pump 8% of wriggling sprays into ethyl cellulose and stearic 95% ethanol, 50 ℃ of oven dry.Coating finishes, discharging 530g.Prescription B:
Contain pill core 500g
Ethyl cellulose 40g
Stearic acid 120g
Polyethylene Glycol-6000 6g
Pulvis Talci 24g
95% ethanol 2400g preparation technology is with prescription A.Prescription C:
Contain pill core 500g
Ethyl cellulose 5g
Eudragit?RS?100???????????????????????????10g
Polyethylene Glycol-6000 2g
Pulvis Talci 1.5g
95% ethanol 150g preparation technology: recipe quantity takes by weighing and contains pill core, pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, CYL 3bar, CAP1 0.9bar, 30 ℃ of inlet air temperature, rotary speed 180rpm, the pump 7% of wriggling sprays into 95% alcoholic solution of ethyl cellulose and Eudragit RS 100.Coating finishes, discharging 510g.Prescription D:
Contain pill core 500g
Ethyl cellulose 40g
Eudragit?RS?100???????????????????????????70g
Polyethylene Glycol-6000 7g
Pulvis Talci 18g
95% ethanol 1800g preparation technology is with prescription C.Prescription E:
Contain pill core 500g
Eudragit?RS?100???????????????????????????10g
Eudragit?RL?100??????????????????????????????10g
Polyethylene Glycol-6000 2g
Pulvis Talci 3g
95% ethanol 300g preparation technology: recipe quantity takes by weighing and contains pill core, pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, CYL 3bar, CAP1 0.9bar, 30 ℃ of inlet air temperature, rotary speed 180rpm, the pump 7% of wriggling sprays into 95% alcoholic solution of EudragitRS 100 and Eudragit RL 100.Coating finishes, discharging 515g.Prescription F:
Contain pill core 500g
Eudragit?RS?100????????????????????????????70g
Eudragit?RL?100????????????????????????????40g
Polyethylene Glycol-6000 7g
Pulvis Talci 12g
95% ethanol 1200g preparation technology is with prescription E.Prescription G:
Contain pill core 500g
Aquacoat 60g
Pulvis Talci 0.4g
Pure water 40g preparation technology: recipe quantity takes by weighing and contains pill core, pours in the hopper.Drive the granulating and coating machine, go into wind pressure 1.0bar, CYL 3bar, CAP1 1.5bar, 55 ℃ of inlet air temperature, rotary speed 180rpm, the pump 5% of wriggling sprays into the pure water solution of Aquacoat.Coating finishes, discharging 520g.Prescription H:
Contain pill core 500g
Aquacoat 180g
Pulvis Talci 1.2g
Pure water 120g preparation technology is with prescription G.
(3) slow-releasing acipimox capsule dissolution determination
Slow-releasing acipimox capsule (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 3ml, put in the 50ml 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 Fig. 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, 125mg/ grain), every day twice, each 3; 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 3 oral administrations can reach ideal blood drug level, have excellent curative.
Table 1: prescription A cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????25 | ????33 | ????41 | ????66 | ????70 | ????81 | ????88 | ????95 |
Table 2: prescription B cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????14 | ????20 | ????31 | ????44 | ????51 | ????61 | ????74 | ????83 |
Table 3: prescription C cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????28 | ????34 | ????48 | ????64 | ????71 | ????82 | ????89 | ????93 |
Table 4: prescription D cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????13 | ????22 | ????36 | ????45 | ????51 | ????63 | ????72 | ????85 |
Table 5: prescription E cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????26 | ????39 | ????47 | ????61 | ????67 | ????75 | ????83 | ????91 |
Table 6: prescription F cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????13 | ????21 | ????34 | ????47 | ????51 | ????63 | ????72 | ????85 |
Table 7: prescription G cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????21 | ????36 | ????41 | ????63 | ????73 | ????79 | ????85 | ????94 |
Table 8: prescription H cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????16 | ????29 | ????38 | ????44 | ????51 | ????65 | ????73 | ????86 |
Claims (6)
1. slow-releasing acipimox capsule is characterized in that its weight is formed to comprise:
100 parts of acipimoxs
158 parts of celphere
0.5～3.7 part of plasticizer
2.6～95 parts of slow-release materials
0～13 part of antiplastering aid
Described slow releasing agent be meant ethyl cellulose (EC), stearic acid, cellulose acetate, Eudragit (acrylic resin) RS 100, Eudragit RL 100, Surelease (basic cellulose aqueous dispersion), Eudragit RS 30D, Eudragit RL 30D, one of Eudragit RS 30D, Eudragit NE 30D or they optional two or more;
Described plasticizer is meant Polyethylene Glycol-6000, diethyl phthalate or triethyl citrate;
Described antiplastering aid is a Pulvis Talci.
2. slow-releasing acipimox capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of acipimoxs
2.6～21 parts of ethyl celluloses
0.5～3.2 part of Polyethylene Glycol-6000
1.6～12.6 parts of Pulvis Talci.
3. slow-releasing acipimox capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of acipimoxs
15.8～63 parts of stearic acid
2.1～8.4 parts of Pulvis Talci.
4. slow-releasing acipimox capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of acipimoxs
100 5.3～36.8 parts of Eudragit RS
1.1～3.7 parts of Polyethylene Glycol-6000
1～7.4 part of Pulvis Talci.
5. slow-releasing acipimox capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of acipimoxs
100 5.3～21 parts of Eudragit RL
1.1～3.7 parts of Polyethylene Glycol-6000
1.6～6.3 parts of Pulvis Talci.
6. slow-releasing acipimox capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of acipimoxs
31.6～94.7 parts of Aquacoats
0.2～0.6 part of Pulvis Talci.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02129443 CN1205933C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing acipimox capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02129443 CN1205933C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing acipimox capsule |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1395927A true CN1395927A (en) | 2003-02-12 |
| CN1205933C CN1205933C (en) | 2005-06-15 |
Family
ID=4746246
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02129443 Expired - Fee Related CN1205933C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing acipimox capsule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1205933C (en) |
Cited By (1)
| 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 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101125134B (en) * | 2006-08-16 | 2010-09-15 | 常州市第四制药厂有限公司 | Hydrochloric tamsulosin sustained-release capsule and its preparation method |
-
2002
- 2002-08-26 CN CN 02129443 patent/CN1205933C/en not_active Expired - Fee Related
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 |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1205933C (en) | 2005-06-15 |
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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 Co., Ltd. Address before: 276003 No. 107, No. 1, Linxi, Shandong, Linyi Patentee before: Lunan Pharmacy Co., Ltd. |
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