CN101642444B - Isosorbide mononitrate double-rate osmotic pump type controlled-release preparation and preparation method thereof - Google Patents
Isosorbide mononitrate double-rate osmotic pump type controlled-release preparation and preparation method thereof Download PDFInfo
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- CN101642444B CN101642444B CN2008101461917A CN200810146191A CN101642444B CN 101642444 B CN101642444 B CN 101642444B CN 2008101461917 A CN2008101461917 A CN 2008101461917A CN 200810146191 A CN200810146191 A CN 200810146191A CN 101642444 B CN101642444 B CN 101642444B
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Abstract
The invention relates to an isosorbide mononitrate double-rate osmotic pump type controlled-release preparation and a preparation method thereof. The preparation mainly comprises a tablet core, a semipermeable coating film, medicament release pores and a mononitrate quick release layer, wherein the tablet core is prepared from the isosorbide mononitrate, a penetrating agent, a filling agent and other pharmaceutic adjuvants; the semipermeable coating film is prepared from cellulose acetate or ethylcellulose, a plasticizer and a pore former; and the quick release layer is prepared from the isosorbide mononitrate, a bonding agent, a lubricating agent and the plasticizer, and the inner layer and the out layer of the quick release layer comprises an isolation thin film coating made of a high molecular material. The quick release part in the prepared controlled-release preparation is fully released in a short time to provide an initial blood concentration; and a controlled-release part takes the osmotic pressure on the inner side and the outer side of a semipermeable film as a driving force, and a medicament is released at a zero level release rate to maintain stable internal blood concentration. The preparation has the characteristics of moderate internal medicament action time, few side effects, and less drug resistance for repeated dose.
Description
Technical field:
The present invention relates to medical technical field, exactly it is a kind of long-term treatment that is used for coronary heart disease, prevention vasospasm type and mixed type angina pectoris, also be applicable to treatment after the myocardial infarction and chronic heart failure long-term treatment-isosorbide mononitrate single layer osmotic pump regulated-release preparations and preparation method thereof.
Background technology:
Isosorbide mononitrate, molecular formula: C
6H
9NO
6Molecular weight: 191.14
Molecular structural formula:
Isosorbide mononitrate can impel vascular smooth muscle loose and distend the blood vessels, and its topmost effect is that venectasia is refluxed to reduce intravenous blood, thereby reduces the loading of heart, and isosorbide mononitrate also makes systemic arterial and main coronary artery expansion.Therefore taking the different Pyrusussuriensis of single nitric acid can reduce the cardiac load amount and promote the oxygen of oxygen confession or balance myocardial ischemia to supply.Be mainly used in the long-term treatment of coronary heart disease clinically, prevention vasospasm type and mixed type angina pectoris also are applicable to the treatment after the myocardial infarction and the long-term treatment of chronic heart failure.
Commercially available preparation comprises conventional tablet and matrix sustained release tablet at present.Commercially available ordinary tablet needs every day takes medicine 2 times; Sustained-release matrix tablets is taken medicine 1 time every day.
Isosorbide mononitrate is the organic acid medicine, is easy to generate the multiple dose drug resistance in the process of medication, must increase dosage after promptly the patient repeatedly takes medicine and just can keep drug effect.Main cause is before being administered into administration in second day the previous day, and left drug can cause that the drug effect of rechallenge reduces, and causes must increasing the dose maintenance drug effect behind the multiple dosing.The elimination half-life is about 5 hours in the body of isosorbide mononitrate.Ordinary tablet is administered twice every day, adopts asymmetric administering mode, promptly carries out administration second time in 7 hours after the administration for the first time, and interval 17 hours between second day the administration first time.Matrix sustained release tablet is administration once a day, and slow-release time is about 20%＜1h＜40%, 45%＜4h＜75%, 8h＞80%.Matrix sustained release tablet is that typical Higuchi (false one-level) discharges, and its release characteristics are that early stage is very fast and the later stage is slower.Because its slow release mechanism is gel skeleton type slow releasing tablet, discharge medicine by corrosion and flooding mechanism, its rate of releasing drug is subjected to such environmental effects such as feed, gastrointestinal motility very big, cause drug release inside and outside dependency poor, individual variation was bigger after the patient took medicine, and was difficult to guarantee patient's drug safety.
Qian Yu (Chinese Pharmaceutical, 2007 the 16th the 5th phases of volume) its research situation of having reported to the isosorbide mononitrate osmotic pump controlled release tablet, dosage is 50mg, use cellulose acetate to be semipermeable membrane material, 2,4,6,8,10, the release in vitro degree measurement result of 12h is respectively 16.2%, 40.6%, 57.0%, 70.5%, 79.2%, 91.5%, but do not provide detailed prescription, can't learn the supplementary product kind and the consumption of its preparation compositions.The shortcoming of this design is that the bigger release of dosage is slower, has increased the burden of organism metabolism, and body residual fraction medicine still is easy to produce drug resistance when causing rechallenge.
Summary of the invention:
The objective of the invention is for a kind of convenient drug administration, stable curative effect, isosorbide mononitrate osmotic pump controlled release preparation that toxic and side effects is little are provided, especially a kind ofly contain the isosorbide mononitrate osmotic pump controlled release preparation that rapid release and controlled release combine.
The object of the present invention is achieved like this:
The invention provides a kind of isosorbide mononitrate osmotic pump preparation that rapid release and controlled release combine that contains, it is characterized in that, by the label that comprises that medicine and osmo active substance, framework material, filler, lubricant are made, its outer film coating that contains the semi-permeable character of macromolecular material, plasticizer and porogen for one deck, and comprise the immediate release drug layer that medicine and adhesive, lubricant, plasticizer are formed, outermost layer can add opacifier by comprising the isolated film clothing that macromolecular material is formed.Wherein, the medicine controlled releasing part is 5: 1～1: 5 with the ratio of immediate release section.Be preferably 2.5: 1～1: 1, most preferred ratio is 7: 3.
Described osmo active substance is selected from one or more of sucrose, sorbitol, mannitol, glucose, lactose, fructose, sodium chloride, potassium chloride, magnesium sulfate, potassium sulfate, sodium sulfate; Described framework material is selected from one or more in polyoxyethylene, ethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, crosslinked sodium carboxymethylcellulose, polyvinylpyrrolidone, the arabic gum, wherein, osmo active substance accounts for 20～70% of label quality, and framework material accounts for 5～20% of label quality.The membrane material that plays the controlled release effect is selected from one or more of cellulose acetate, ethyl cellulose, acrylic resin, hydroxypropyl emthylcellulose, polyethylene, polyethylene glycols, phthalate, citrate, Hair two diethyl phthalates, preferred, ethyl and cellulose acetate; Described filler is selected from one or more in lactose, sucrose, starch, cellulose, the dextrin; Described lubricant is selected from one or more in magnesium stearate, Pulvis Talci, starch, the paraffin; Described adhesive is selected from a kind of usefulness in polyvinylpyrrolidone, methylcellulose, the hydroxypropyl methylcellulose or several; Described wetting agent comprises the ethanol-water solution of water, dehydrated alcohol, various concentration; Porogen comprises sucrose, mannitol, Polyethylene Glycol (polyethylene glycol 1500, Macrogol 2000, Macrogol 4000, polyethylene glycol 6000) etc.; Plasticizer comprises Methyl Benzene-o-dicarboxylate and/or triethyl citrate, diethyl phthalate, Hair two diethyl phthalates, Polyethylene Glycol; Opacifier comprises titanium dioxide, Pulvis Talci, silicon dioxide.
Above-mentionedly contain the isosorbide mononitrate osmotic pump preparation that rapid release and controlled release combine, can make double speed release type osmotic pump tablet, double speed release type pore type osmotic pumps, see accompanying drawing 1,2.
Isosorbide mononitrate osmotic pump controlled release tablet of the present invention, can produce according to the preparation method of the known general osmotic pump preparation of pharmaceuticals industry, drug release hole at the one or both sides of coated tablet is laser boring, mechanical punching or compacting hole packaging technique, and the aperture is 0.2～1.2 millimeter.
Advantage of the present invention is: compare with conventional tablet, that this preparation only needs be administered once, act in one day is lasting, stable curative effect, toxic and side effects are little; Compare with common slow releasing tablet, controlled release tablet can more effective control drug release, and inside and outside difference is little, and medicine is subjected to such environmental effects such as gastrointestinal tract pH value, wriggling little in vivo, and drug effect is more stable.Compare with common controlled release preparation, rapid release/controlled release osmotic pump controlled release tablet can reach effective blood drug concentration fast at rapid release portion medicine of the initial stage of taking medicine, the performance drug effect, then controlled release partly continues and discharges medicine consistently, keeps effective blood drug concentration, and drug effect not only rapidly but also lasting.In addition, because the medicine of initial release 30%, at once participate in metabolism, make and take medicine the later stage that (16～24h) organism metabolism medication amount reduce greatly, the residual quantity of medicine obviously reduces during the next day administration, effectively avoid and delay the chemical sproof generation of multiple dose, can effectively reduce the using dosage of medicine, and then alleviate the burden of organism metabolism medicine.
The problem that exists during according to the pharmacokinetic characteristics of isosorbide mononitrate and clinical application, we improve heavy dose of isosorbide mononitrate preparation.We discover, isosorbide mononitrate t
1/2About 5h, gastrointestinal absorption rapidly and fully, mainly with the original shape medicine through renal metabolism, the conventional tablet of using can't be realized the effective blood medicine of long term maintenance slow release, need be administered twice every day, though and common slow releasing preparation preparation has been realized administration once a day, but because in the onset rapidly of administration baseline medicine, may miss best drug treating time for patients with coronary heart disease, in addition because the residual quantity of the slow release of medicine medicine when having increased the next day administration, induce body to produce drug resistance easily, therefore ideal isosorbide mononitrate preparation should be: in the onset rapidly of administration initial stage, can keep effective blood drug concentration after reaching effective blood drug concentration, and remain on the residual quantity of relatively low level medicine when reducing the next day administration, effectively avoid chemical sproof generation.The design that combines of our rapid release that adopts in prescription when design of the heavy dose of isosorbide mononitrate of design and slow release for this reason, the part drug encapsulation is formed release layer outside the controlled release label, discharge immediately at the initial stage release layer medicine of taking medicine and to be absorbed by the body, form effectively initial blood drug level fast, reach therapeutic effect rapidly, this point is most important for coronary heart disease and anginal acute attack patient, has reached the identical big peak time of blood drug level and the therapeutic effect at administration initial stage of conventional tablet; Another part medicine is made the controlled release label, slowly discharges and keeps blood drug level.Because initial blood drug level is bigger, more common slow releasing preparation has long blood drug level plateau under the same dose situation, peak concentration is significantly less than slow releasing preparation and common single chamber controlled release preparation, and during rechallenge, drug disposition is residual again less than the slow releasing preparation of same dose, the effective acting time of prolong drug to greatest extent, can reduce chemical sproof generation again, we also screen the ratio of rapid release and controlled release emphatically, by screening to controlled release/immediate release section drug ratios, adoptable ratio is 5: 1～1: 5, be preferably 2.5: 1～1: 1, most preferred ratio is 7: 3.As embodiment 1 (accompanying drawing 7), shown in the begle dog time front of blood concentration of the two release formulations of same dose and the single-dose of slow releasing preparation and conventional tablet, two release formulations reach the peak rapidly at the administration initial stage, its peak time Tmax is about 0.8h, and common slow releasing preparation peak time is about 4.5h, and reach peak concentration Cmax and be starkly lower than common slow releasing preparation, minimum blood drug level Cmin is starkly lower than common slow releasing tablet, and experimental result has reached the designing requirement of expection.Compare with ordinary preparation, reduced the fluctuation of blood drug level, and prolonged the time of keeping blood drug level, and reduced Cmin significantly, realized dosage regimen once a day, the compliance that has improved patient's medication has greatly reduced simultaneously chemical sproof generation again.Because the isosorbide mononitrate preparation of listing has a plurality of dosage at present, therefore we have designed the preparation of the double speed osmotic pumps of 50mg simultaneously, and its pharmacokinetic property studied, shown in embodiment 3 (accompanying drawing 8), the double speed controlled release tablet of 50mg dosage and the slow releasing agent of 40mg have close Cmin, and Cmax is lower than common slow releasing preparation simultaneously.Because therefore the residual quantity of medicine does not increase the probability that drug resistance that escalated dose causes increases when increasing dosage and not increasing the next day administration, the patient for needs increasing dosage provides a good selection.
Because isosorbide mononitrate easily distils, therefore the problem that content reduces often appears in conventional tablet and slow releasing tablet, immediate release section for this preparation, avoid single nitre distillation difficulty very big, adopted the contagion gown prescription of HMPC among the present invention in conjunction with the polyvidone ester, outer wrapping contagion gown in release layer, the medicine that has effectively suppressed immediate release section is guaranteed stable content to label and outer migration.
The present invention has also used domestic existing pharmaceutic adjuvant ethyl cellulose, has avoided using the cellulose acetate of import, has reduced production cost, and has helped the production domesticization of osmotic pump preparation, breaks the situation of external drugmaker monopolization osmotic pump preparation.
Controlled release preparation of the present invention will be used for the long-term treatment of coronary heart disease clinically, and prevention vasospasm type and mixed type angina pectoris also are applicable to the treatment after the myocardial infarction and the long-term treatment of chronic heart failure.
Prescription is main to be formed:
Isosorbide mononitrate 10～40g
Osmo active substance 30～200g
Play the membrane material 5～30g of controlled release effect
Other adjuvant 1～10g
Make 1000
Description of drawings:
Fig. 1 double speed release type osmotic pump tablet sketch map
Fig. 2 double speed release type pore type osmotic pump tablet sketch map
Fig. 3 is according to the releasing curve diagram of the isosorbide mononitrate monolayer controlled release tablet of embodiment 1 preparation
Fig. 4 is according to the releasing curve diagram of the isosorbide mononitrate monolayer controlled release tablet of embodiment 2 preparations
Fig. 5 is according to the releasing curve diagram of the isosorbide mononitrate monolayer controlled release tablet of embodiment 3 preparations
Fig. 6 is according to the releasing curve diagram of the isosorbide mononitrate monolayer controlled release tablet of embodiment 4 preparations
Fig. 7 list nitre rapid release/controlled release tablet and slow releasing tablet and ordinary tablet begle dog blood drug level-time graph (embodiment 1)
Fig. 8 list nitre controlled release tablet and slow releasing tablet begle dog blood drug level-time graph (embodiment 3)
The specific embodiment:
Embodiment 1: the present embodiment that adopts oneself method known of pharmaceuticals industry to make.
Tablet contains following composition by weight percentage:
Label is formed:
Isosorbide mononitrate 28g
Lactose 150g
Mannitol 40g
Hydroxypropyl methylcellulose 20g
Magnesium stearate 3g
3% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution are an amount of
Be prepared into 1000
The semipermeable membrane coating solution is formed:
Cellulose acetate 8g
Macrogol 4000 4g
Diethyl phthalate 2g
Water 10ml
Ethanol 50ml
Acetone 140ml
Coating weightening finish 6%
The immediate release drug layer is formed:
Isosorbide mononitrate 3g
HPMC 5g
Ethanol 40ml
Water 60ml
The contagion gown coating solution is formed:
Hydroxypropyl methylcellulose 6cp 2g
Macrogol 4000 1g
Pulvis Talci 1g
Titanium dioxide 1g
Ethanol/water (40/60) 100ml
Adopt film-coated technique, isosorbide mononitrate is made mono-layer osmotic pump controlled release tablets, it is simultaneously carried out laser or mechanical punching, aperture 0.5mm is to reach the purpose of controlled release.In the extracorporeal releasing test, almost all dissolving is complete at the preceding 0.5h that discharges for the immediate release drug layer, and controlled release drug is to discharge near the slow-paced of zero level, and release profiles as shown in Figure 3.As shown in Figure 7, the begle dog single-dose pharmacokinetics test of carrying out according to isosorbide mononitrate osmotic pump sheet and commercially available single nitre slow releasing tablet of embodiment 1 preparation shows, the initial blood drug level of double speed controlled release tablet is apparently higher than slow releasing tablet, peak time is about 0.5 hour, cmax value is starkly lower than slow releasing tablet, and 24h blood drug level is lower than slow releasing tablet after the administration.
Embodiment 2: the present embodiment that adopts the known method of pharmaceuticals industry to make.
Tablet contains following composition by weight percentage:
Label is formed:
Isosorbide mononitrate 28g
Lactose 150g
Mannitol 40g
Hydroxypropyl methylcellulose 40g
Magnesium stearate 3g
3% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution are an amount of
Be prepared into 1000
The semipermeable membrane coating solution is formed:
Cellulose acetate 8g
Macrogol 4000 4g
Diethyl phthalate 1.5ml
Water 10ml
Ethanol 50ml
Acetone 140ml
The immediate release drug layer is formed:
Isosorbide mononitrate 3g
HPMC 6g
Ethanol 40ml
Water 60ml
The contagion gown coating solution is formed:
Hydroxypropyl methylcellulose 6cp 3g
Polyvidone ester 3g
Macrogol 4000 1.5g
Pulvis Talci 1g
Titanium dioxide 1g
Ethanol/water (40/60) 100ml
Adopt film-coated technique, isosorbide mononitrate is made double speed pore type osmotic pump controlled release tablet, in release medium, porogen in the semi-transparent clothing film is met water dissolution and is formed small drug release hole, label discharges near zero level, immediate release drug layer 0.5h in release medium all discharges fully, and release profiles as shown in Figure 4.
Embodiment 3: the present embodiment that adopts the known method of pharmaceuticals industry to make.
Tablet contains following composition by weight percentage:
Label is formed:
Isosorbide mononitrate 28g
Lactose 150g
Mannitol 40g
Magnesium stearate 3g
Eudragit NE-30D is an amount of
Be prepared into 1000
The semipermeable membrane coating solution is formed:
Ethyl cellulose 3.0g
Macrogol 4000 0.6g
HPMC 0.6g
Ethanol/water (80/20) 100ml
The immediate release drug layer is formed:
Isosorbide mononitrate 3g
HPMC 6g
Ethanol 40ml
Water 60ml
The contagion gown coating solution is formed:
Hydroxypropyl methylcellulose 6cp 3g
Polyvidone ester 3g
Macrogol 4000 1.5g
Pulvis Talci 1g
Titanium dioxide 1g
Ethanol/water (40/60) 100ml
Adopt film-coated technique, isosorbide mononitrate is made double speed pore type osmotic pump controlled release tablet, in release medium, porogen in the semi-transparent clothing film is met water dissolution and is formed small drug release hole, label discharges near zero level, immediate release drug layer 0.5h in release medium all discharges fully, and release profiles as shown in Figure 5.As shown in Figure 8, the begle dog single-dose pharmacokinetics test of carrying out according to isosorbide mononitrate osmotic pump sheet and commercially available single nitre slow releasing tablet of embodiment 3 preparations shows, the initial blood drug level of double speed controlled release tablet is apparently higher than slow releasing tablet, peak time is about 0.8 hour, cmax value is starkly lower than slow releasing tablet, and 24h blood drug level is lower than slow releasing tablet after the administration.
Embodiment 4: the present embodiment that adopts the known method of pharmaceuticals industry to make.
Tablet contains following composition by weight percentage:
Label is formed:
Isosorbide mononitrate 25g
Lactose 150g
Mannitol 40g
Hydroxypropyl methylcellulose 20g
Magnesium stearate 3g
3% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution are an amount of
Be prepared into 1000
The semipermeable membrane coating solution is formed:
Cellulose acetate 8g
Macrogol 4000 4g
HPMC 2.0g
Diethyl phthalate 1.5ml
Ethanol/water (80/20) 400ml
The immediate release drug layer is formed:
Isosorbide mononitrate 3g
HPMC 5g
Ethanol 40ml
Water 60ml
The contagion gown coating solution is formed:
Hydroxypropyl methylcellulose 6cp 2g
Macrogol 4000 1g
Pulvis Talci 1g
Titanium dioxide 1g
Ethanol/water (40/60) 100ml
Adopt film-coated technique, isosorbide mononitrate is made mono-layer osmotic pump controlled release tablets, it is simultaneously carried out laser or mechanical punching, aperture 0.5mm is to reach the purpose of controlled release.In the extracorporeal releasing test, almost all dissolving is complete at the preceding 0.5h that discharges for the immediate release drug layer, and controlled release drug is to discharge near the slow-paced of zero level, and release profiles as shown in Figure 6.
Claims (6)
1. double speed controlled releasing penetrant pump that contains isosorbide mononitrate comprises following structure from inside to outside:
1) label of making by medicine and osmo active substance, framework material, filler, lubricant, described osmo active substance is selected from one or more in sucrose, sorbitol, mannitol, glucose, lactose, fructose, sodium chloride, potassium chloride, magnesium sulfate, potassium sulfate, the sodium sulfate; Described framework material is selected from one or more in polyoxyethylene, ethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpyrrolidone, the arabic gum, described filler is selected from one or more in lactose, sucrose, starch, cellulose, the dextrin, and described lubricant is selected from one or more in magnesium stearate, Pulvis Talci, starch, the paraffin; Wherein, osmo active substance accounts for 20～70% of label quality, and framework material accounts for 5～20% of label quality;
2) contain macromolecular material for one deck outside the label, the film coating of the semi-permeable character of plasticizer and porogen, described macromolecular material has been the membrane material of controlled release effect, be selected from cellulose acetate, ethyl cellulose, acrylic resin, hydroxypropyl emthylcellulose, in the polyethylene one or more, described porogen is selected from sucrose, mannitol, polyethylene glycol 1500, Macrogol 2000, Macrogol 4000, one or more of polyethylene glycol 6000, described plasticizer is selected from Methyl Benzene-o-dicarboxylate and/or triethyl citrate, diethyl phthalate, ethyl sebacate, in the Polyethylene Glycol one or more;
3) outermost layer is the immediate release drug layer of being made up of medicine and binding agent, lubricant, described lubricant is selected from one or more in magnesium stearate, Pulvis Talci, starch, the paraffin, and described binding agent is selected from one or more in polyvinylpyrrolidone, methylcellulose, the hydroxypropyl methylcellulose;
It is characterized in that described immediate release drug layer inside and outside all has the contagion gown film, described contagion gown film is made up of hydroxypropyl methylcellulose, polyvidone ester, titanium dioxide, Pulvis Talci.
2. controlled releasing penetrant pump according to claim 1 is characterized in that 2) described in play the controlled release effect membrane material be ethyl cellulose.
3. controlled releasing penetrant pump according to claim 1 is characterized in that containing following composition:
Label is formed:
The semipermeable membrane coating solution is formed:
The immediate release drug layer is formed:
The contagion gown coating solution is formed:
4. controlled releasing penetrant pump according to claim 1 is characterized in that containing following composition:
Label is formed:
The semipermeable membrane coating solution is formed:
The immediate release drug layer is formed:
The contagion gown coating solution is formed:
5. controlled releasing penetrant pump according to claim 1 is characterized in that containing following composition:
Label is formed:
The semipermeable membrane coating solution is formed:
The immediate release drug layer is formed:
The contagion gown coating solution is formed:
6. controlled releasing penetrant pump according to claim 1 is characterized in that containing following composition:
Label is formed:
The semipermeable membrane coating solution is formed:
The immediate release drug layer is formed:
The contagion gown coating solution is formed:
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101461917A CN101642444B (en) | 2008-08-08 | 2008-08-08 | Isosorbide mononitrate double-rate osmotic pump type controlled-release preparation and preparation method thereof |
| HK10107657.7A HK1141228A1 (en) | 2008-08-08 | 2010-08-10 | Isosorbide mononitrate double-rate osmotic pump type controlled-release formulation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101461917A CN101642444B (en) | 2008-08-08 | 2008-08-08 | Isosorbide mononitrate double-rate osmotic pump type controlled-release preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101642444A CN101642444A (en) | 2010-02-10 |
| CN101642444B true CN101642444B (en) | 2011-09-21 |
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|---|---|---|---|
| CN2008101461917A Active CN101642444B (en) | 2008-08-08 | 2008-08-08 | Isosorbide mononitrate double-rate osmotic pump type controlled-release preparation and preparation method thereof |
Country Status (2)
| Country | Link |
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| CN (1) | CN101642444B (en) |
| HK (1) | HK1141228A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670543A (en) * | 2011-03-17 | 2012-09-19 | 北京天衡药物研究院 | Osmotic pump isosorbide mononitrate quick-controlled release tablet |
| CN102319224B (en) * | 2011-07-27 | 2013-03-20 | 赛乐医药科技(上海)有限公司 | Compound methoxyphenamine rapid-release slow-release osmotic pump preparation |
| CN109316467A (en) * | 2018-01-31 | 2019-02-12 | 合肥合源药业有限公司 | Isosorbide Mononitrate spansule and preparation method thereof |
| CN117427043A (en) * | 2022-07-21 | 2024-01-23 | 越洋医药开发(广州)有限公司 | Biphase controlled release preparation and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1846693A (en) * | 2005-04-12 | 2006-10-18 | 潘卫三 | Control released permeation bump tablet of venlafaxine hydrochloride and its prepn process |
| CN1923184A (en) * | 2006-10-16 | 2007-03-07 | 北京科信必成医药科技发展有限公司 | Multiple apertures releasing osmosis pump and preparation process thereof |
-
2008
- 2008-08-08 CN CN2008101461917A patent/CN101642444B/en active Active
-
2010
- 2010-08-10 HK HK10107657.7A patent/HK1141228A1/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1846693A (en) * | 2005-04-12 | 2006-10-18 | 潘卫三 | Control released permeation bump tablet of venlafaxine hydrochloride and its prepn process |
| CN1923184A (en) * | 2006-10-16 | 2007-03-07 | 北京科信必成医药科技发展有限公司 | Multiple apertures releasing osmosis pump and preparation process thereof |
Non-Patent Citations (3)
| Title |
|---|
| 张宇等.《单硝酸异山梨醋渗透泵型控释片的制备及体外释药机制考察》.《中国新药杂志》.2007,第16卷(第21期),第1784-1785页. * |
| 杨泗兴等.《星点设计2效应面法优化单硝酸异山梨酯微孔渗透泵片处方》.《药学与临床研究》.2008,第16卷(第3期),第175-178页. * |
| 钱渝.《单硝酸异山梨酯渗透泵控释片的研制》.《中国药业》.2007,第16卷(第5期),第32-33页. * |
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| Publication number | Publication date |
|---|---|
| CN101642444A (en) | 2010-02-10 |
| HK1141228A1 (en) | 2010-11-05 |
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