CN101627977A - Double-layer osmotic pump controlled-release medicinal composition of barnidipine or physiologically acceptable salt of barnidipine - Google Patents
Double-layer osmotic pump controlled-release medicinal composition of barnidipine or physiologically acceptable salt of barnidipine Download PDFInfo
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- CN101627977A CN101627977A CN200810116775A CN200810116775A CN101627977A CN 101627977 A CN101627977 A CN 101627977A CN 200810116775 A CN200810116775 A CN 200810116775A CN 200810116775 A CN200810116775 A CN 200810116775A CN 101627977 A CN101627977 A CN 101627977A
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Abstract
The invention discloses a double-layer osmotic pump controlled-release medicinal composition of barnidipine or physiologically acceptable salt of barnidipine. The medicinal composition consists of a double-layer tablet core and a coating film; the double-layer tablet core contains barnidipine or physiologically acceptable salt of barnidipine with effective dose and pharmaceutically acceptable medical auxiliary materials; and the coating film is a semipermeable film containing or not containing a hole making agent. The double-layer osmotic pump controlled-release medicinal composition of barnidipine or physiologically acceptable salt of barnidipine can effectively control the release of the medicaments in a specific time, reduce the medicament-taking frequency, and stabilize in vivo blood drug level, so that during the medicament-taking period, a patient is ensured to keep stable and effective in vivo blood drug level, and the safety and the effectiveness of the medicament and the compliance of the patient are fundamentally improved.
Description
Technical field
The present invention relates to the double-layer osmotic pump controlled-release medicinal composition of a kind of antihypertensive drug barnidipine or its physiologically acceptable salt, controlled release tablet release of the present invention is complete, the safety and the effectiveness of medication have been improved, characteristics such as it has, and convenient drug administration, effect are lasting, stable curative effect, toxic and side effects are little.The invention belongs to field of medicaments.
Technical background
Calcium ion antagonist (or claiming calcium ion channel blockor) has been widely used in hypertensive treatment.Its resisting hypertension effect is similar to beta receptor-blocker, angiotensin converting enzyme (ACE) inhibitor and thiazide diuretic.Existing studies show that, two pyridinium hydroxides (DHP) calcium ion antagonist can reduce old systolic hypertension patient occurrence of stroke, and such medicine has become this type of patient group's recommended drug.And such medicine also can be used as the alternative medication of the angiotensin-convertion enzyme inhibitor of treatment hypertension and systolic heart failure.The drug combination of DHP calcium ion antagonist and beta receptor-blocker and ACE inhibitor is the very effective scheme of treatment hypertension.And also in long-acting DHP calcium ion antagonist, do not observe and fugitive calcium ion antagonist such as the relevant cardiovascular side effects of nifedipine at present.
YM-09730-5 (Barnidipine Hydrochloride) is first single optical isomer in the dihydropyridine class calcium antagonist, can pass through function cells film transmembrane potential dependency calcium channel specifically, suppress calcium ion and flow in the cell, optionally make the smooth muscle loosening of peripheral blood vessel and crown blood vessel.In various hypertension models (spontaneous hypertension rat, renal hypertensive rat and DOCA-Sal load Hypertensive Rats), YM-09730-5 demonstrates persistent, remarkable hypotensive effect.Drug resistance does not appear in long term administration yet.After primary hypertension patient is taken this product, do not influence the rhythm and pace of moving things of variation round the clock of blood pressure, took medicine 1 time in 1 day, excessively do not reduce the blood pressure at night, and hypotensive effect can continue 24 hours.In addition, confirmed that YM-09730-5 also has inhibitory action to the rising that plays blood pressure morning next day.For the anesthesia Canis familiaris L., reduce the effect enhancing of peripheral blood vessel and coronary vascular resistance along with the increase of consumption.In addition, blood vessels such as coronary artery dilator, vertebral artery, femoral artery and renal artery increase the blood flow of these internal organs.In primary hypertension patient, can significantly reduce whole peripheral blood vessels, kidney blood vessel and liver vessel resistance.At normal saline load spontaneous hypertension rat, YM-09730-5 can make electrolyte excretion amount increase in urine amount and the urine, and sodium in the urine/potassium ratio raises simultaneously.In the renal artery medicine-feeding test of anesthesia Canis familiaris L., under low dosage, the sodium that YM-09730-5 can suppress renal tubules absorbs again; Under the high dose, but renal blood flow increasing and glomerular filtration rate.Easily send out in the Hypertensive Rats test at nothing anesthesia apoplexy, YM-09730-5 can suppress the hypertensive cerebral pathological changes of kidney and blood vessel.
The osmotic pump preparation of Chu Xianing is nineteen fifty-five two Australian scholar's inventions the earliest, be used for the administration of domestic animal gastrointestinal, it comprises: coyote hole (drug chamber), salt chamber (salt chamber) and 3 chambers of hydroecium (water chamber), and the elastic diaphragm (elastic diaphragm) between the rigidity semipermeable membrane between hydroecium and salt chamber (rigid semi-permeable membrane), salt chamber and coyote hole, 6 major parts such as rigid film of whole device outsourcing, volume reaches 80cm
3The device of this Rose-Nelson of being referred to as type osmotic pumps utilizes the permeable pressure head between hydroecium and salt chamber, makes water enter the salt chamber from semipermeable membrane, thereby causes salt chamber volume expanded, and the elastic diaphragm on extruding right side forces medicine to disengage from the tapping of coyote hole.As osmotic pump type preparation the earliest, there is a great shortcoming in such device, that is: water is in case enter the salt chamber by semipermeable membrane, just will cause drug release process, this means this device in case make, just must use immediately, and can't preserve, although in the patent of delivering afterwards, this device has been carried out bigger improvement (increased impervious envelope film between hydroecium and salt chamber, face with preceding it is smashed), but because of this class device technique too complicated, volume is too huge, so be not suitable for further developing as the human preparation.
Enter phase early 1970s, Alza company simplifies on the basis of Rose-Nelson type osmotic pumps, has released the Higuchi-Leeper type osmotic pumps that suction enters the salt chamber from external environment, and volume-diminished is 35cm
3About.Subsequently, developed Higuchi-Theeuwes type osmotic pumps again, it comprises: the elastic diaphragm between salt chamber, coyote hole, two Room and the rigidity semipermeable membrane of outsourcing, its volume significantly reduces, and is 3cm
3About; Its greatest improvement part is: it changes the impermeability peplos of whole device into semipermeable membrane, thereby has established crucial basis for the further simplification of osmotic pump preparation.On this basis, 1974, Theeuwes proposed the notion and the structure of elementary single chamber type osmotic pumps, and osmotic pump preparation is simplified becomes the simple form of ordinary coating sheet, thereby made it to have moved towards suitability for industrialized production and clinical practice application.In this device, removed isolating salt chamber, change into the permeability that utilizes medicine self and some permeation-promoter be used for provide power for release: in use, moisture sucks in the sheet from semipermeable membrane, make and form very high osmotic pressure in the sheet, thereby the saturated aqueous solution that makes medicine in the sheet is disengaged by the aperture on sheet surface, because the no ductility of used semipermeable membrane (mostly being cellulose acetate), volume in the film remains constant, so as long as solid drugs not dissolving fully as yet in the sheet, its saturated solution will be released continuously, thereby reach the effect of constant speed release medicine.
Compare with common slow releasing preparation, controlled release preparation has: drug release behavior is not subjected to factor affecting such as media environment pH value, enzyme, gastrointestinal peristalsis, food, and the inside and outside dependency is good; The bigger phenomenon of blood concentration fluctuation can be avoided or reduce to its unique release mode to greatest extent, reduces toxic and side effects; Obviously reduce medicining times, improve compliance and effectiveness that patient takes medicine; With high content of technology, be developed into advantages such as power is higher, the construction cycle is short.
For this reason, the invention provides the YM-09730-5 double-layer osmotic pump controlled-release tablet, controlled release tablet release of the present invention is complete, has improved the safety and the effectiveness of medication, and the present invention has simultaneously determined preferred prescription composition by the screening to prescription.
Summary of the invention
The barnidipine or its physiologically acceptable salt double-layer osmotic pump controlled-release medicinal composition that the purpose of this invention is to provide a kind of stable and drug safety of medicine release.Characteristics such as it has that convenient drug administration, effect are lasting, stable curative effect, toxic and side effects are little.
Barnidipine of the present invention or its physiologically acceptable salt double-layer osmotic pump controlled-release medicinal composition thing, its structure is double-deck label outsourcing coating membrane, described double-deck label is made up of medicated layer and boosting layer, double-deck label outsourcing has coating membrane, coating membrane has a small delivery aperture in medicated layer one side, and the drug release hole diameter is about 0.1～1.2 millimeter.
Controlled release pharmaceutical compositions of the present invention, be made up of effective dose barnidipine or its physiologically acceptable salt and pharmaceutically acceptable excipient, pharmaceutically acceptable excipient is selected from one or more in surfactant, osmotic pressure active substance, penetrating agent, coloring agent, lubricant, wetting agent, binding agent, filmogen, porogen, the plasticizer.
Wherein said barnidipine or its physiologically acceptable salt effective dose are 5mg～40mg, are preferably 10mg～20mg, and its physiologically acceptable salt of barnidipine is preferably hydrochlorate.
Wherein said surfactant is selected from one or more in sodium lauryl sulphate, Stepanol MG, poloxamer or the tween.
Wherein said penetrating agent is selected from that polyoxyethylene, hydroxypropyl methylcellulose, ethyl cellulose, methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, carboxymethyl starch are received, low-substituted hydroxypropyl cellulose, sodium alginate, cross-linking sodium carboxymethyl cellulose, cross linked polyvinyl pyrrolidone, carbopol one or more.
Wherein said osmotic pressure active substance be selected from sodium chloride, potassium chloride, lactose, mannitol, fructose, glucose, sucrose one or more.
Wherein said binding agent can be selected from starch slurry, polyvidone, crospolyvinylpyrrolidone, hydroxypropyl methylcellulose and/or other cellulose families one or more.
Wherein said wetting agent can be selected from water, methanol, ethanol, dehydrated alcohol, chloroform, dichloromethane, acetone one or more.
Described lubricant can be selected from magnesium stearate, stearic acid, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols, month hangs pure magnesium sulfate, starch, paraffin one or more.
Wherein the optional autoxidation ferrum of coloring agent, iron oxide red, iron oxide yellow, amaranth, carmine, erythrosine, newly red, the lemon yellow of red, the red pigment of cowberry of red, beet red, lac, capsanthin, red rice, sunset yellow, indigo Huang, light blue one or more, and for strengthening the various pigments of the acid pigment of above-mentioned water solublity dispersibility in oils and fats.
Wherein said porogen be selected from sucrose, mannitol, Polyethylene Glycol, polyvidone, copolyvidone, dibutyl sebacate one or more.
Wherein said plasticizer be selected from Methyl Benzene-o-dicarboxylate, ethyl phthalate, diethyl phthalate, poly-phthalic acid vinyl acetate, polyvinyl alcohol, polystyrene, carbopol, polrvinyl chloride, dioctyl phthalate, triethyl citrate, Polyethylene Glycol, polyvidone, copolyvidone, dibutyl sebacate one or more.
Wherein said filmogen can be selected from ethyl cellulose, starch, methylcellulose, cellulose acetate, cellulose diacetate, Triafol T, acrylic resin, Opadry, Sulisi one or more.
Wherein said filmogen be dissolved in one or more solution in water, methanol, ethanol, dehydrated alcohol, chloroform, dichloromethane, acetone, the benzene etc.
Be used for the present invention prepare the active component of barnidipine or its physiologically acceptable salt double-layer osmotic pump controlled-release medicinal composition and pharmaceutically the acceptable excipient be to form by following proportioning (accounting for the weight ratio of double-deck label):
The weight ratio that medicated layer constituent accounts for double-deck label is:
Barnidipine or its physiologically acceptable salt are 1～20%
The osmotic pressure active substance is 0～60%
Penetrating agent is 5～60%
Surfactant is 0～15%
Binding agent is 0～20%
Lubricant is 0～5%
The weight ratio that the constituent of boosting layer accounts for double-deck label is:
Penetrating agent is 5～60%
The osmotic pressure active substance is 0～60%
Binding agent is 0～20%
Lubricant is 0～5%
Coloring agent is 0.1～5%
The weight ratio that coating membrane constituent accounts for double-deck label is:
Filmogen is 1～30%
Porogen is 0～5%
Plasticizer is 0.1～5%
Wherein said controlled release pharmaceutical compositions coating membrane is about 0.1～1.2 millimeter at the drug release hole diameter of medicated layer one side.
The preparation method of barnidipine of the present invention or its physiologically acceptable salt double-layer osmotic pump controlled-release medicinal composition.Comprise following steps:
(1) granulate behind the mix homogeneously in pharmaceutic adjuvants such as barnidipine or its physiologically acceptable salt and penetrating agent are sifted out back, promptly gets the medicated layer granule.
(2) pharmaceutic adjuvants such as penetrating agent, osmotic pressure active substance are sifted out granulate behind the mix homogeneously, promptly get boosting layer granule.
(3) medicated layer granule and boosting layer granule are worth the double-layer tablet label behind the secondary tabletting, with the coating solution coating system predetermined weight that contains filmogen, porogen and/or plasticizer, with laser boring or machine punching, the drug release hole diameter is about 0.1～1.2 millimeter, promptly in medicated layer one side.
Advantages such as the present invention preferably writes out a prescription to form and is listed in the embodiments of the invention, and these are preferably write out a prescription and obtain through screening, and it is more stable compared with prior art to have quality, and release is more complete, side effect is little.
The specific embodiment
Below further set forth the present invention by embodiment, but and unrestricted the present invention.
Embodiment 1
Medicated layer
Barnidipine 10g
Polyoxyethylene 60g
Pulvis Talci 1g
The boosting layer
Polyoxyethylene 30g
Sodium chloride 10g
Hydroxypropyl methylcellulose 5g
Iron oxide red 0.5g
Pulvis Talci 0.5g
Make 1000
Coating fluid prescription (1000 consumptions)
Triafol T 15g
Polyethylene Glycol 1g
Ethyl phthalate 1.5g
Dichloromethane is an amount of
Preparation method:
1, according to recipe quantity granulated behind the mix homogeneously in barnidipine, polyoxyethylene, the Pulvis Talci back of sifting out, promptly get the medicated layer granule.
2, polyoxyethylene, sodium chloride, hydroxypropyl methylcellulose, iron oxide red, Pulvis Talci are sifted out and are granulated behind the mix homogeneously, promptly get boosting layer granule.
3, with medicated layer granule and boosting layer granule through the secondary tabletting or adopt double-deck sheeting equipment, make the double-layer tablet label, standby.
4, coating solution preparation: Triafol T, Polyethylene Glycol and ethyl phthalate are added in an amount of dichloromethane solution, stir and make it whole dissolvings, standby.
5, the double-layer tablet label that makes is put in the high-efficiency coating machine, at the uniform velocity sprayed into the coating solution coating, get the transparent coating double-layer tablet.
6, punch with laser boring or machine in medicated layer one side, the drug release hole diameter is about 0.6 millimeter, promptly.
Medicated layer
YM-09730-5 15g
Polyoxyethylene 100g
Hydroxypropyl methylcellulose 15g
Polyvidone 5g
Magnesium stearate 1.5g
Dehydrated alcohol is an amount of
The boosting layer
Polyoxyethylene 50g
Potassium chloride 20g
Hydroxypropyl cellulose 10g
Polyvidone 5g
Ferrum oxide 1g
Magnesium stearate 1g
Dehydrated alcohol is an amount of
Make 1000
Coating fluid prescription (1000 consumptions)
Cellulose acetate 30g
Polyethylene Glycol 3g
Carbopol 3g
Chloroform is an amount of
Preparation method:
1, recipe quantity YM-09730-5, polyvidone are dissolved in an amount of dehydrated alcohol, mix homogeneously, standby.
2, polyoxyethylene, hydroxypropyl methylcellulose are sifted out back mix homogeneously adds YM-09730-5 polyvidone ethanol solution, adopts wet granulation, adds magnesium stearate, promptly gets the medicated layer granule.
3, will adopt wet granulation behind polyoxyethylene, potassium chloride, hydroxypropyl cellulose, polyvidone, the ferrum oxide mix homogeneously, add magnesium stearate, promptly get boosting layer granule.
4, with medicated layer granule and boosting layer granule through the secondary tabletting or adopt double-deck sheeting equipment, make the double-layer tablet label, standby.
5, coating solution preparation: cellulose acetate, Polyethylene Glycol and carbopol are added in an amount of chloroform soln, stir and make it whole dissolvings, standby.
6, the double-layer tablet label that makes is put in the high-efficiency coating machine, at the uniform velocity sprayed into the coating solution coating, get the transparent coating double-layer tablet.
7, punch with laser boring or machine in medicated layer one side, the drug release hole diameter is about 0.55 millimeter, promptly.
Embodiment 3
Medicated layer
YM-09730-5 10g
Polyoxyethylene 90g
Sodium alginate 15g
Sucrose 10g
Polyvidone 5g
Stearic acid 2g
80% ethanol is an amount of
The boosting layer
Polyoxyethylene 60g
Sodium chloride 30g
Ethyl cellulose 10g
Polyvidone 5g
Iron oxide red 2g
Stearic acid 2g
80% ethanol is an amount of
Make 1000
Coating fluid prescription (1000 consumptions)
Cellulose diacetate 50g
Sucrose 5g
Poly-phthalic acid vinyl acetate 5g
Ester
Dichloromethane is an amount of
Preparation method:
1, recipe quantity YM-09730-5, polyvidone are dissolved in the 80% an amount of ethanol, mix homogeneously volatilizes solution, gets YM-09730-5 polyvidone powder.
2, with YM-09730-5 polyvidone powder, polyoxyethylene, sodium alginate, sucrose mix homogeneously, add stearic acid, promptly get the medicated layer granule.
3, with behind polyoxyethylene, sodium chloride, ethyl cellulose, polyvidone, the iron oxide red mix homogeneously, add stearic acid, promptly get boosting layer granule.
4, with medicated layer granule and boosting layer granule through the secondary tabletting or adopt double-deck sheeting equipment, make the double-layer tablet label, standby.
5, coating solution preparation: cellulose diacetate, Polyethylene Glycol and poly-phthalic acid vinyl acetate are added in an amount of dichloromethane solution, stir and make it whole dissolvings, standby.
6, the double-layer tablet label that makes is put in the high-efficiency coating machine, at the uniform velocity sprayed into the coating solution coating, get the transparent coating double-layer tablet.
7, punch with laser boring or machine in medicated layer one side, the drug release hole diameter is about 0.55 millimeter, promptly.
Medicated layer
YM-09730-5 10g
Polyoxyethylene 80g
Hydroxypropyl methylcellulose 20g
Copolyvidone 6g
Stearic acid 2g
90% ethanol is an amount of
The boosting layer
Polyoxyethylene 60g
Sodium chloride 30g
Ethyl cellulose 10g
Copolyvidone 5g
Iron oxide red 2g
Stearic acid 1g
90% ethanol is an amount of
Make 1000
Coating fluid prescription (1000 consumptions)
Cellulose diacetate 40g
Polyethylene Glycol 5g
Diethyl phthalate 4g
Acetone is an amount of
Preparation method is with embodiment 3.
The YM-09730-5 controlled release tablet of four embodiment preparations is as follows with the contrast of YM-09730-5 slow releasing capsule release characteristic:
Concrete release profiles is seen accompanying drawing 1.
Claims (12)
1, a kind of barnidipine or its physiologically acceptable salt double-layer osmotic pump controlled-release medicinal composition of containing, its structure is double-deck label outsourcing coating membrane, described double-deck label is made up of medicated layer and boosting layer, and double-deck label outsourcing has coating membrane, and coating membrane has a small delivery aperture in medicated layer one side.
2, claim 1 described controlled release pharmaceutical compositions, be made up of effective dose barnidipine or its physiologically acceptable salt and pharmaceutically acceptable excipient, pharmaceutically acceptable excipient is selected from one or more in surfactant, osmotic pressure active substance, penetrating agent, coloring agent, lubricant, wetting agent, binding agent, filmogen, porogen, the plasticizer.
3, each described controlled release pharmaceutical compositions during aforesaid right requires is characterized in that, counts by weight percentage:
The weight ratio that medicated layer constituent accounts for double-deck label is:
Barnidipine or its physiologically acceptable salt are 1～20%
The osmotic pressure active substance is 0～60%
Penetrating agent is 5～60%
Surfactant is 0～15%
Binding agent is 0～20%
Lubricant is 0～5%
The weight ratio that the constituent of boosting layer accounts for double-deck label is:
Penetrating agent is 5～60%
The osmotic pressure active substance is 0～60%
Binding agent is 0～20%
Lubricant is 0～5%
Coloring agent is 0.1～1%
The weight ratio that coating membrane constituent accounts for double-deck label is:
Filmogen is 1～30%
Porogen is 0～5%
Plasticizer is 0.1～10%
4, each described controlled release pharmaceutical compositions during aforesaid right requires, barnidipine or its physiologically acceptable salt effective dose are 5mg～40mg, are preferably 10mg～20mg, its physiologically acceptable salt of barnidipine is preferably hydrochlorate.
5, each described controlled release pharmaceutical compositions during aforesaid right requires is characterized in that:
Described surfactant is selected from one or more in sodium lauryl sulphate, Stepanol MG, poloxamer or the tween.
Described penetrating agent is selected from that polyoxyethylene, hydroxypropyl methylcellulose, ethyl cellulose, methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, carboxymethyl starch are received, low-substituted hydroxypropyl cellulose, sodium alginate, cross-linking sodium carboxymethyl cellulose, cross linked polyvinyl pyrrolidone, carbopol one or more.
Described osmotic pressure active substance be selected from sodium chloride, potassium chloride, lactose, mannitol, fructose, glucose, sucrose one or more.
Described binding agent can be selected from starch slurry, polyvidone, crospolyvinylpyrrolidone, hydroxypropyl methylcellulose and/or other cellulose families one or more.
Described wetting agent can be selected from water, methanol, ethanol, dehydrated alcohol, chloroform, dichloromethane, acetone one or more.
Described lubricant can be selected from magnesium stearate, stearic acid, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols, month hangs pure magnesium sulfate, starch, paraffin one or more.
The optional autoxidation ferrum of coloring agent, iron oxide red, iron oxide yellow, amaranth, carmine, erythrosine, newly red, the lemon yellow of red, the red pigment of cowberry of red, beet red, lac, capsanthin, red rice, sunset yellow, indigo Huang, light blue one or more, and for strengthening the various pigments of the acid pigment of above-mentioned water solublity dispersibility in oils and fats.
Described porogen be selected from sucrose, mannitol, Polyethylene Glycol, polyvidone, copolyvidone, dibutyl sebacate one or more.
Described plasticizer be selected from Methyl Benzene-o-dicarboxylate, ethyl phthalate, diethyl phthalate, poly-phthalic acid vinyl acetate, polyvinyl alcohol, polystyrene, carbopol, polrvinyl chloride, dioctyl phthalate, triethyl citrate, Polyethylene Glycol, polyvidone, copolyvidone, dibutyl sebacate one or more.
Described filmogen can be selected from ethyl cellulose, starch, methylcellulose, cellulose acetate, cellulose diacetate, Triafol T, acrylic resin, Opadry, Sulisi one or more.Described filmogen be dissolved in one or more solution in water, methanol, ethanol, dehydrated alcohol, chloroform, dichloromethane, acetone, the benzene etc.
6, aforesaid right requires each described controlled release pharmaceutical compositions among the 1-5, it is characterized in that calculating by weight, and it consists of:
Medicated layer
Barnidipine 10g
Polyoxyethylene 60g
Pulvis Talci 1g
The boosting layer
Polyoxyethylene 30g
Sodium chloride 10g
Hydroxypropyl methylcellulose 5g
Iron oxide red 0.5g
Pulvis Talci 0.5g
Make 1000
Coating fluid prescription (1000 consumptions)
Triafol T 15g
Polyethylene Glycol 1g
Ethyl phthalate 1.5g
Dichloromethane is an amount of
7, aforesaid right requires the controlled release pharmaceutical compositions described in the 1-5, it is characterized in that calculating by weight, and it consists of:
Medicated layer
YM-09730-5 15g
Polyoxyethylene 100g
Hydroxypropyl methylcellulose 15g
Polyvidone 5g
Magnesium stearate 1.5g
Dehydrated alcohol is an amount of
The boosting layer
Polyoxyethylene 50g
Potassium chloride 20g
Hydroxypropyl cellulose 10g
Polyvidone 5g
Ferrum oxide 1g
Magnesium stearate 1g
Make 1000
Coating fluid prescription (1000 consumptions)
Cellulose acetate 30g
Polyethylene Glycol 3g
Carbopol 3g
Chloroform is an amount of
8, aforesaid right requires the controlled release pharmaceutical compositions described in the 1-5, it is characterized in that calculating by weight, and it consists of:
Medicated layer
YM-09730-5 10g
Polyoxyethylene 90g
Sodium alginate 15g
Sucrose 10g
Polyvidone 5g
Stearic acid 2g
80% ethanol is an amount of
The boosting layer
Polyoxyethylene 60g
Sodium chloride 30g
Ethyl cellulose 10g
Polyvidone 5g
Iron oxide red 2g
Stearic acid 2g
Make 1000
Coating fluid prescription (1000 consumptions)
Cellulose diacetate 50g
Sucrose 5g
Poly-phthalic acid vinyl acetate 5g
Ester
Dichloromethane is an amount of
9, aforesaid right requires the controlled release pharmaceutical compositions described in the 1-5, it is characterized in that calculating by weight, and it consists of:
Medicated layer
YM-09730-5 10g
Polyoxyethylene 80g
Hydroxypropyl methylcellulose 20g
Copolyvidone 6g
Stearic acid 2g
90% ethanol is an amount of
The boosting layer
Polyoxyethylene 60g
Sodium chloride 30g
Ethyl cellulose 10g
Copolyvidone 5g
Iron oxide red 2g
Stearic acid 1g
Make 1000
Coating fluid prescription (1000 consumptions)
Cellulose diacetate 40g
Polyethylene Glycol 5g
Diethyl phthalate 4g
Acetone is an amount of
10, the preparation method of each described controlled release pharmaceutical compositions during aforesaid right requires comprises following steps:
(1) granulate behind the mix homogeneously in pharmaceutic adjuvants such as barnidipine or its physiologically acceptable salt and penetrating agent are sifted out back, promptly gets the medicated layer granule.
(2) pharmaceutic adjuvants such as penetrating agent, osmotic pressure active substance are sifted out granulate behind the mix homogeneously, promptly get boosting layer granule.
(3) medicated layer granule and boosting layer granule are worth the double-layer tablet label behind the secondary tabletting, with the coating solution coating system predetermined weight that contains filmogen, porogen and/or plasticizer, with laser boring or machine punching, the drug release hole diameter is about 0.1～1.2 millimeter, promptly in medicated layer one side.
11, each described controlled release pharmaceutical compositions in the above-mentioned claim is characterized in that, the drug release hole diameter of coating membrane on the medicated layer surface is about 0.1～1.2 millimeter.
12, each described controlled release pharmaceutical compositions in the above-mentioned claim is characterized in that, the drug release hole diameter of coating membrane on the medicated layer surface is about 0.5 millimeter.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810116775A CN101627977A (en) | 2008-07-17 | 2008-07-17 | Double-layer osmotic pump controlled-release medicinal composition of barnidipine or physiologically acceptable salt of barnidipine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810116775A CN101627977A (en) | 2008-07-17 | 2008-07-17 | Double-layer osmotic pump controlled-release medicinal composition of barnidipine or physiologically acceptable salt of barnidipine |
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|---|---|---|---|
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102846574A (en) * | 2012-10-10 | 2013-01-02 | 德州德药制药有限公司 | Nifedipine controlled release composition and preparation method thereof |
| CN110025589A (en) * | 2019-01-16 | 2019-07-19 | 武汉长联来福制药股份有限公司 | A kind of sodium ferulate controlled release tablet and preparation method thereof |
-
2008
- 2008-07-17 CN CN200810116775A patent/CN101627977A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102846574A (en) * | 2012-10-10 | 2013-01-02 | 德州德药制药有限公司 | Nifedipine controlled release composition and preparation method thereof |
| CN102846574B (en) * | 2012-10-10 | 2014-08-27 | 德州德药制药有限公司 | Nifedipine controlled release composition and preparation method thereof |
| CN110025589A (en) * | 2019-01-16 | 2019-07-19 | 武汉长联来福制药股份有限公司 | A kind of sodium ferulate controlled release tablet and preparation method thereof |
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