CN101658521A - Paracetamol, pseudoephedrine and chlorphenamine compound sustained release preparation - Google Patents
Paracetamol, pseudoephedrine and chlorphenamine compound sustained release preparation Download PDFInfo
- Publication number
- CN101658521A CN101658521A CN200810118865A CN200810118865A CN101658521A CN 101658521 A CN101658521 A CN 101658521A CN 200810118865 A CN200810118865 A CN 200810118865A CN 200810118865 A CN200810118865 A CN 200810118865A CN 101658521 A CN101658521 A CN 101658521A
- Authority
- CN
- China
- Prior art keywords
- pseudoephedrine
- physiologically acceptable
- acceptable salt
- cellulose
- chlorphenamine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention relates to a sustained release preparation taking paracetamol and pseudoephedrine or physiologically acceptable salts thereof, and chlorphenamine or physiologically acceptable salts thereof as active components, and provides a compound preparation which can comprehensively overcome cold related symptoms and of which all the active components are slowly released.
Description
Technical field
The present invention relates to a kind of slow releasing preparation that is active component with acetaminophen, pseudoephedrine or its physiologically acceptable salt and chlorphenamine or its physiologically acceptable salt, belong to field of medicaments.
Background technology
Flu is the upper respiratory tract mucosa infection that is caused by a lot of dissimilar viruses, and its cardinal symptom often is nasal obstruction, sneeze, slight throat pain and heating etc., and systemic symptom has whole body discomfort, headache and myalgia etc.Because of no specific therapy can be sayed,, can only adopt symptomatic treatment to impel many remissions of flu so virus is firm then unnecessary.Because therefore the many symptoms that also do not have a kind of agents alleviate and deposit have various compound preparations to go on the market successively.These compound preparations select for use the medicine composition compound recipe of different curative effects to be used to alleviate simultaneous different symptoms.There is multiple symptom as patient,, then suits the medicine to the illness and use suitable compound preparation than more suitable with several individual event medicines, also more economical sometimes particularly at common cold initial stage.
Acetaminophen is an acetophenone amine dipron thing.By suppressing Cycloxygenase, improve the threshold of pain and produce analgesic activity, selectivity suppresses the synthetic of hypothalamus thermotaxic centre prostaglandin, cause peripheral blood vessel expansion, perspire and reach refrigeration function, its refrigeration function intensity is suitable with aspirin, but can generation with aspirin and contain the relevant side effect of aspirin product.By suppressing the synthetic of prostaglandin etc. and discharge, improve the threshold of pain and play analgesic activity, belong to the periphery analgesic, effect is than a little less than the aspirin, only to light, moderate pain is effective.This product does not have the obvious anti-inflammatory and anti effect.
Pseudoephedrine claims d-pseudephedrine again, is the optical isomer of ephedrine, and the two is by extracting gained in Herba Ephedrae or the ephedra equisetina grass, but synthetic at present.Pseudoephedrine discharges norepinephrine by stimulating SNE, play sympatheticomimetic action indirectly, its preventing respiratory is identical with the effect and the ephedrine of nasal congestion, but boosting only is 1/5 of an ephedrine, strengthening heart rate and pressor effect only is 1/4 of ephedrine, aspect the expansion bronchus smooth muscle only be its 1/2.The pseudoephedrine vasoconstrictive has certain selectivity, mainly shrinks the upper respiratory tract blood vessel and makes and breathe unobstructedly, is used to shrink nasal mucosa vessels alleviating the nasal obstruction symptom, and is evident in efficacy and side effect is little, in the use usually with its hydrochlorate or sulfate.
Chlorphenamine is H
1Receptor antagonist, the antihistamine drug that belongs to early stage classics is used for the treatment of anaphylactic disease, for example: seasonality and chronic rhinitis, urticaria and pruritus clinically mainly with the treatment anaphylactic disease.Usually show in various degree like sympathetic, medmain, calmness and similar cholinolytic side effect, can cause feel sleepy, xerostomia, the dimness of vision etc., common its maleate of using in the use.
Acetaminophen, pseudoephedrine and chlorphenamine are prepared into slow releasing preparation, can alleviate owing to heating, headache, upper airway symptoms and the sinusitis that common cold, influenza cause, the various symptoms due to the pollinosis, particularly suitable and the early stage clinical symptoms of alleviating above-mentioned disease are as symptoms such as sneeze, rhinorrhea, nasal obstructions.Because acetyl aminophenol, pseudoephedrine and chlorphenamine using dosage, rate of release, the difference of aspects such as absorbance need provide a kind of both releases, absorption to reach synchronous, so that better play synergistic compound preparation, reduce the medication number of times and make things convenient for patient's medication.
Summary of the invention
The purpose of this invention is to provide and a kind ofly can overcome the relevant symptom of flu comprehensively, and all active component all are the compound preparation that slow release discharges.Technical solution of the present invention is as follows:
The slow releasing preparation that is active component with acetaminophen, pseudoephedrine or its physiologically acceptable salt and chlorphenamine or its physiologically acceptable salt of the present invention, comprise delivery system, described delivery system is made up of the label that drug slow is discharged and/or ball core and coating, part or all is present in described active component in label and/or the ball core, and the active component remainder is present in the coating.Described acetaminophen, pseudoephedrine or its physiologically acceptable salt all are slow release and discharge.Described " part ", can be one of in two kinds of active component or two, or one of in two kinds of active component or a part of two.Slow releasing preparation of the present invention contains acetaminophen 10-1000mg in each dosage unit, preferred 200-1000mg, pseudoephedrine or its physiologically acceptable salt 5-90mg, preferred 20-90mg, chlorphenamine or its physiologically acceptable salt 1-36mg, preferred 2-12mg.
The physiologically acceptable salt of pseudoephedrine of the present invention and the physiologically acceptable salt of chlorphenamine, comprise acylate or inorganic acid salt, wherein the physiologically acceptable salt of pseudoephedrine is preferably hydrochlorate or sulfate, and the physiologically acceptable salt of described chlorphenamine is preferably maleate.
Label of the present invention and/or ball core are by hydroxypropyl methylcellulose, the Sulisi aqueous dispersion, the water solublity coating powder, polyvinylpyrrolidone, ethyl cellulose, methylcellulose, Hydroxypropyl Methylcellulose Phathalate, cellulose acetate-phthalate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, hexadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, hydroxy methocel, polyvinyl alcohol, poly-phthalic acid vinyl acetate, polystyrene, carbopol, polrvinyl chloride, octadecanol, diethyl phthalate, dioctyl phthalate, Polyethylene Glycol, sodium alginate, chitosan, gelatin, Lac, pectin, guar gum, sucrose, lactose, starch, dextrin, Icing Sugar, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose, mannitol, microcrystalline Cellulose, pregelatinized Starch, in the titanium dioxide one or more are made.
During coating of the present invention is compared by ethyl cellulose, starch, Aquacoat, methylcellulose, cellulose acetate, cellulose diacetate, Triafol T, acrylic resin, Opadry, Su Li one or more are made.
Preparation of the present invention contains lubricant, and described lubricant is one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols, month pure magnesium sulfate of extension.
The release characteristic of acetaminophen is in the preparation of the present invention: 1h:25-65%, 2h:55-85% is more than the 4h:80%, more than the 8h:90%.
The release characteristic of pseudoephedrine or its physiologically acceptable salt is in the preparation of the present invention: 1h:20-65%, 2h:42-85%, 4h:60-90%, 8h: be not less than 70%.
The release characteristic of chlorphenamine or its physiologically acceptable salt is in the preparation of the present invention: 1h:30-65%, 2h:40-80%, 4h:60-90%, 8h: be not less than 80%.
Preparation of the present invention is tablet, granule, pill, capsule or suspensoid.
Slow releasing preparation of the present invention, can not only overcome the relevant symptom of flu comprehensively, the performance synergistic interaction effect of compound drugs, and the release of three kinds of active component of slow releasing preparation of the present invention, absorb and to reach synchronously, it obtains desired drug release behavior in vivo and in vitro.Such drug release behavior can reduce takes number of times (by original 4 times on the one reduce to a day twice, promptly take night and morning).Therefore this preparation has the advantages that the medication number of times is few, medicine slowly discharges in vivo, blood drug level is steady, fluctuation is little, bioavailability is high, safe.
Specific embodiment
By following examples the slow releasing preparation that is active component with acetaminophen, pseudoephedrine or its physiologically acceptable salt and chlorphenamine or its physiologically acceptable salt of the present invention is done further to specify, but not as limitation of the present invention.
Embodiment 1
Prescription:
Acetaminophen 325g
Pseudoephedrine hydrochloride 90g
Chlorphenamine maleate 4g
Hydroxypropyl methylcellulose 40g
Brazil wax 15g
Microcrystalline Cellulose 36g
10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is an amount of
Magnesium stearate is an amount of
Opadry 15g
Pure water is an amount of
?????????????????????????????????????????
Make 1000 (grain/bags)
Preparation method 1:
(1) particulate preparation Brazil wax, hydroxypropyl methylcellulose, microcrystalline Cellulose are crossed 80 mesh sieves, mix homogeneously respectively.Add pseudoephedrine hydrochloride, chlorphenamine maleate, acetaminophen more successively, abundant mixing is with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 50 ℃ of dryings, 20 mesh sieve granulate, standby.
(2) preparation of coating solution adds to Opadry in the pure water, and adds pure water to 100ml, stirs 1 hour, and is standby.
(3) get (1) granule and carry out coating, obtain coated granule.
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet.
(5) in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, gets final product coated tablet.
(6) get (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
(7) get (3) gained granule direct packaging, promptly get granule.
Preparation method 2:
(1) particulate preparation Brazil wax 25g, hydroxypropyl methylcellulose 10g, microcrystalline Cellulose 26g cross 80 mesh sieves, mix homogeneously respectively.Add pseudoephedrine hydrochloride, the abundant mixing of chlorphenamine maleate more successively, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 50 ℃ of dryings, 20 mesh sieve granulate add an amount of magnesium stearate, and are standby.
(2) with the remaining Brazil wax of recipe quantity, hydroxypropyl methylcellulose, microcrystalline Cellulose and the abundant mix homogeneously of acetaminophen, add an amount of magnesium stearate, standby.
(3) preparation of coating solution adds to Opadry in the pure water, and adds pure water to 100ml, stirs 1 hour, and is standby.
(4) granule with (1), (2) gained is pressed into double-layer tablet, gets (3) coating solution, is wrapped in outside the tablet, get final product double-layer coating plate.
The release characteristic of active component is as shown in table 1 in the gained different dosage form.
The release characteristic of active component in table 1 different dosage form
Embodiment 2
Prescription:
Acetaminophen 325g
Pseudoephedrine hydrochloride 90g
Chlorphenamine maleate 4g
Hydroxypropyl methylcellulose K100M 30g
Hydroxypropyl methylcellulose E5 75g
Microcrystalline Cellulose 45g
10% copolyvidone K
30Aqueous solution is an amount of
Stearic acid is an amount of
Opadry 50g
Water is an amount of to dissolving fully
?????????????????????????????????????
Make 1000 (grain/bags)
Preparation method 1:
(1) particulate preparation hydroxypropyl methylcellulose, microcrystalline Cellulose, cross 80 mesh sieves respectively,, add pseudoephedrine hydrochloride, acetaminophen, the chlorphenamine maleate 2g of recipe quantity again with the abundant mixing of equivalent incremental method, make its mix homogeneously, with 10% copolyvidone K
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate, standby.
(2) preparation of coating solution adds to chlorphenamine maleate 2g, Opadry in the pure water, and adds pure water to 100ml, stirs 0.5 hour, and is standby.
(3) get (1) granule and carry out coating, obtain coated granule.
(4) in (3) gained granule, add an amount of stearic acid, mix homogeneously, tabletting promptly gets tablet I.
(5) in (1) gained granule, add an amount of stearic acid, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, can coated tablet I.
(6) get (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
(7) get (3) gained granule direct packaging, promptly get granule.
Preparation method 2:
(1) hydroxypropyl methylcellulose K100M 15g, hydroxypropyl methylcellulose E520g, microcrystalline Cellulose 35g cross 80 mesh sieves respectively, and mix homogeneously adds pseudoephedrine hydrochloride, the chlorphenamine maleate 2g of recipe quantity again, makes its mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate, standby.
(2) get in the prescription remaining hydroxypropyl methylcellulose, microcrystalline Cellulose, acetaminophen and cross 80 mesh sieves, mix homogeneously is with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate, standby.
(3) preparation of coating solution adds to chlorphenamine maleate 2g, Opadry in the pure water, and adds pure water to 100ml, stirs 0.5 hour, and is standby.
(4) get (1) granule and carry out coating, obtain coated granule.
(5) in (2), (4) gained granule, add an amount of stearic acid respectively, mix homogeneously, the compacting double-layer tablet promptly gets tablet II.
(6) in (1), (2) gained granule, add an amount of stearic acid respectively, mix homogeneously, the compacting double-layer tablet is got (3) coating solution, is wrapped in outside the tablet, can coated tablet II.
The release characteristic of active component is as shown in table 2 in the gained different dosage form.
The release characteristic of active component in table 2 different dosage form
Embodiment 3
Prescription:
| Pseudoephedrine sulfate | ??90g |
| Chlorphenamine maleate | ??2g |
| Acetaminophen | ??325g |
| Sodium alginate | ??60g |
| Gelatin | ??58g |
| Pregelatinized Starch | ??50g |
| 10% 30 POVIDONE K 30 BP/USP 25Aqueous solution | In right amount |
| Magnesium stearate | In right amount |
The coating prescription:
| Pseudoephedrine sulfate | ?30g |
| Chlorphenamine maleate | ?2g |
| Opadry | ?50g |
| Ethanol | An amount of to dissolving fully |
Make 1000 (grain/bags)
Preparation method:
(1) 100 mesh sieves are crossed in particulate preparation sodium alginate, gelatin, pregelatinized Starch respectively, with the abundant mixing of equivalent incremental method, add pseudoephedrine sulfate, chlorphenamine maleate, the acetaminophen of recipe quantity again, and mix homogeneously is with 10% 30 POVIDONE K 30 BP/USP
25Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 45 ℃ of dryings, 20 mesh sieve granulate, standby.
(2) preparation of coating solution is got pseudoephedrine sulfate and chlorphenamine maleate is dissolved in the ethanol, adds Opadry, and mix homogeneously is standby.
(3) get (1) granule and carry out coating, obtain coated granule.
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet.
(5) in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, gets final product coated tablet.
(6) get (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
(7) get (3) gained granule direct packaging, promptly get granule.
The release characteristic of active component is as shown in table 3 in the gained different dosage form.
The release characteristic of active component in table 3 different dosage form
Embodiment 4
Prescription:
| Pseudoephedrine sulfate | ?90g |
| Chlorphenamine maleate | ??4.0g |
| Acetaminophen | ??325g |
| Celphere | ??105g |
| Hydroxypropyl methylcellulose E5 | ??6g |
| The Sulisi solid content | ??30g |
| The water solublity coating powder | ??5g |
| Titanium dioxide | ??1g |
| Stearic acid | ??5g |
| 30 POVIDONE K 30 BP/USP 30 | In right amount |
| Water | In right amount |
| Dehydrated alcohol | In right amount |
The coating prescription:
| Opadry | ??30g |
| Water | Add to 1000ml |
Make 1000 (sheets)
Preparation method:
(1) pseudoephedrine sulfate slow-release micro-pill
I, preparation 10%HPMC E5 aqueous solution, standby;
II, get the Sulisi solid content and add water, shake up standby;
III, preparation contain the water solublity coating solution of water solublity coating powder 10%, titanium dioxide 1%;
IV, preparation 40% pseudoephedrine sulfate aqueous solution add above-mentioned HPMC solution again, stir evenly standby;
V, get the celphere coating, spray step IV gained solution is collected micropill to finishing;
VI, to pseudoephedrine sulfate micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again.
Promptly get pseudoephedrine sulfate medicine-feeding micropill, standby.
(2) chlorphenamine maleate slow-release micro-pill
I, preparation 10%HPMC E5 aqueous solution;
II, get the chlorphenamine maleate of recipe quantity, stir down and join in the purified water, add HPMC solution again, stir under the tepor condition and make it all standby after the dissolving;
III, get celphere, bag chlorphenamine maleate solution earlier, temperature of charge is controlled at 38 ± 2 ℃, with a spot of purified water (about 20 milliliters) detergent line, wraps remaining HPMC E5 solution again, and temperature of charge is controlled at 38 ± 2 ℃, and micropill is received in dry back;
IV, get the Sulisi solid content, the thin up preparation contains the aqueous dispersion of solid content 25%, the weightening finish coating according to 8%;
V, the chlorphenamine maleate micropill is placed fluid bed bag Sulisi slow release layer earlier, 30 ± 2 ℃ of control temperature of charge;
VI, coating finish rear curing time and temperature is one hour, 80 ℃, collects micropill.
Promptly get the chlorphenamine maleate slow-release micro-pill, standby.
(3) acetaminophen slow-release micro-pill preparation
I, an amount of 30 POVIDONE K 30 BP/USP 30 is added an amount of dehydrated alcohol be made into 3% (w/w) solution, standby;
II, stearic acid is added an amount of dehydrated alcohol be mixed with 5% (w/w) solution, standby;
III, get an amount of recipe quantity celphere and put in the coating pan;
IV, take by weighing the stearic acid ethanol solution for preparing and be sprayed on the celphere;
V, spray 30 POVIDONE K 30 BP/USP 30 ethanol solutions successively, the hydrojet intermission also adds acetaminophen, treats that acetaminophen adheres to the ball wicking surface and repeats said process again, finishes until adding powder;
VI, take out and to make micropill in 45 ℃ of dryings 12 hours;
VII, sieve with 14 mesh sieves and 20 orders.
Promptly get the acetaminophen slow-release micro-pill, standby.
(4) preparation of coating solution: 30g adds in the pure water with Opadry, and adds pure water to 100ml, stirs 1 hour.
(5) get (1), (2) (3) micropill carries out coating, obtains coated granule.
(6) in (5) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet.
(7) in (1), (2) (3) gained micropill, add an amount of magnesium stearate, mix homogeneously, tabletting is got (4) coating solution, is wrapped in outside the tablet, gets final product coated tablet.
(8) get (1), (2) (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
(9) get (1), (2) (3) gained granule direct packaging, promptly get granule.
The release characteristic of active component is as shown in table 4 in the gained different dosage form.
The release characteristic of active component in table 4 different dosage form
Embodiment 5
Prescription:
| Pseudoephedrine sulfate | ??120g |
| Chlorphenamine maleate | ??4g |
| Acetaminophen | ??325g |
| Celphere | ??100g |
| Hydroxypropyl methylcellulose E5 | ??6g |
| Hydroxypropyl methylcellulose E4MP | ??40g |
| The Sulisi solid content | ??30g |
| The water solublity coating powder | ??5g |
| Titanium dioxide | ??1g |
| Lactose | ??60g |
| 30 POVIDONE K 30 BP/USP 90 | In right amount |
| Water | In right amount |
| Dehydrated alcohol | In right amount |
| The moon is hung pure magnesium sulfate | In right amount |
The coating prescription:
| Opadry II | ??25g |
| Pure water | Add to 1000ml |
Make 1000 (sheets)
Preparation method:
(1) the plain sheet preparation of acetaminophen slow release
It is evenly mixed to get the hydroxypropyl emthylcellulose E4MP, acetaminophen, the lactose that claim recipe quantity successively, and the moon that adds recipe quantity is hung pure magnesium sulfate mix homogeneously, surveys intermediate, tabletting, promptly;
(2) pseudoephedrine sulfate slow-release micro-pill
I, preparation 10%HPMC E5 aqueous solution, standby;
II, get the Sulisi solid content and add water, shake up standby;
III, preparation contain the water solublity coating solution of water solublity coating powder 10%, titanium dioxide 1%;
IV, preparation 40% pseudoephedrine sulfate aqueous solution add above-mentioned HPMC solution again, stir evenly standby;
V, get the celphere coating, spray step IV gained solution is collected micropill to finishing;
VI, to pseudoephedrine sulfate micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again.
Promptly get pseudoephedrine sulfate medicine-feeding micropill, standby.
(3) chlorphenamine maleate slow-release micro-pill
I, preparation 10%HPMC E5 aqueous solution;
II, get the chlorphenamine maleate of recipe quantity, stir down and join in the purified water, add HPMC solution again, stir under the tepor condition and make it all standby after the dissolving;
III, get celphere, bag chlorphenamine maleate solution earlier, temperature of charge is controlled at 38 ± 2 ℃, with a spot of purified water (about 20 milliliters) detergent line, wraps remaining HPMC E5 solution again, and temperature of charge is controlled at 38 ± 2 ℃, and micropill is received in dry back;
IV, get the Sulisi solid content, the thin up preparation contains the aqueous dispersion of solid content 25%, the weightening finish coating according to 8%;
V, the chlorphenamine maleate micropill is placed fluid bed bag Sulisi slow release layer earlier, 30 ± 2 ℃ of control temperature of charge;
VI, coating finish rear curing time and temperature is one hour, 80 ℃, collects micropill.
Promptly get the chlorphenamine maleate slow-release micro-pill, standby.
(4) Opadry is added in the pure water, and add pure water, stirred 0.5 hour to 100ml, standby.
(5) get (2) (3) gained micropill and add an amount of month pure magnesium sulfate of extension, mix homogeneously, tabletting, be pressed into double-layer tablet with (1) gained sheet again, the plain sheet that makes is put to high-efficiency coating machine, be heated to about 50 ℃, at the uniform velocity spray into the coating solution coating, make plain sheet temperature remain on 45-50 ℃,, be drying to obtain double-layer coating plate until evenly wrapping the thin film clothing.
(6) the plain sheet that (1) is made is put to high-efficiency coating machine, is heated to about 50 ℃, at the uniform velocity sprays into the coating solution coating, makes plain sheet temperature remain on 45-50 ℃, until evenly wrapping the thin film clothing, is drying to obtain.
(7) get (6), (2) (3) gained coated tablet, micropill fills in the hungry area softgel shell, promptly gets capsule.
(8) get (2) (3) gained micropill and add an amount of month pure magnesium sulfate of extension respectively, mix homogeneously, be pressed into three-layer tablet with (1) gained sheet again, the plain sheet that makes is put to high-efficiency coating machine, be heated to about 55 ℃, at the uniform velocity spray into the coating solution coating, make plain sheet temperature remain on 50-55 ℃, until evenly wrapping the thin film clothing, be drying to obtain three layers of coated tablet.
The release characteristic of active component is as shown in table 5 in the gained different dosage form
The release characteristic of active component in table 5 different dosage form
Claims (9)
1, a kind of compound slow release preparation that is active component with acetaminophen, pseudoephedrine or its physiologically acceptable salt and chlorphenamine or its physiologically acceptable salt, it comprises a kind of delivery system, it is characterized in that: described delivery system is made up of the label that drug slow is discharged and/or ball core and/or coating, part or all is present in described active component in label and/or the ball core, and the remainder of active component is present in the coating.
2, compound slow release preparation according to claim 1 is characterized in that: acetaminophen, pseudoephedrine or its physiologically acceptable salt and chlorphenamine or its physiologically acceptable salt all are slow release and discharge.
3, compound slow release preparation according to claim 1, it is characterized in that: contain acetaminophen 10-1000mg in each dosage unit, preferred 200-1000mg, pseudoephedrine or its physiologically acceptable salt 5-90mg, preferred 20-90mg, chlorphenamine or its physiologically acceptable salt 1-36mg, preferred 2-12mg.
4, according to the described compound slow release preparation of claim 1-3, it is characterized in that: the physiologically acceptable salt of described pseudoephedrine is pseudoephedrine hydrochlorate or pseudoephedrine sulfate; The physiologically acceptable salt of described chlorphenamine is the chlorphenamine maleate.
5, according to the described compound slow release preparation of claim 1-4, it is characterized in that: described label and/or ball core are by hydroxypropyl methylcellulose, the Sulisi aqueous dispersion, the water solublity coating powder, polyvinylpyrrolidone, ethyl cellulose, methylcellulose, Hydroxypropyl Methylcellulose Phathalate, cellulose acetate-phthalate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, hexadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, hydroxy methocel, polyvinyl alcohol, poly-phthalic acid vinyl acetate, polystyrene, carbopol, polrvinyl chloride, octadecanol, diethyl phthalate, dioctyl phthalate, Polyethylene Glycol, sodium alginate, chitosan, gelatin, Lac, pectin, guar gum, sucrose, lactose, starch, dextrin, Icing Sugar, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose, mannitol, microcrystalline Cellulose, pregelatinized Starch, in the titanium dioxide one or more are made.
6, according to the described compound slow release preparation of claim 1-5, it is characterized in that: one or more during described coating is compared by ethyl cellulose, starch, Aquacoat, methylcellulose, cellulose acetate, cellulose diacetate, Triafol T, acrylic resin, Opadry, Su Li are made.
7, according to the described compound slow release preparation of claim 1-6, be characterised in that: described preparation contains lubricant, and described lubricant is selected from one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols, month pure magnesium sulfate of extension.
8, according to the described compound slow release preparation of claim 1-7, it is characterized in that:
The release characteristic of acetaminophen is: 1h:25-65%, 2h:55-85% is more than the 4h:80%, more than the 8h:90%.
The release characteristic of pseudoephedrine or its physiologically acceptable salt is: 1h:20-65%, 2h:42-85%, 4h:60-90%, 8h: be not less than 70%.
The release characteristic of chlorphenamine or its physiologically acceptable salt is: 1h:30-65%, 2h:40-80%, 4h:60-90%, 8h: be not less than 80%.
9, according to the described compound slow release preparation of claim 1-8, it is characterized in that: described preparation is tablet, granule, pill, capsule or suspensoid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810118865A CN101658521A (en) | 2008-08-26 | 2008-08-26 | Paracetamol, pseudoephedrine and chlorphenamine compound sustained release preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810118865A CN101658521A (en) | 2008-08-26 | 2008-08-26 | Paracetamol, pseudoephedrine and chlorphenamine compound sustained release preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101658521A true CN101658521A (en) | 2010-03-03 |
Family
ID=41786922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810118865A Pending CN101658521A (en) | 2008-08-26 | 2008-08-26 | Paracetamol, pseudoephedrine and chlorphenamine compound sustained release preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101658521A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103156849A (en) * | 2013-03-21 | 2013-06-19 | 青岛正大海尔制药有限公司 | Compound pseudoephedrine hydrochloride enteric-coated tablet and preparation method thereof |
-
2008
- 2008-08-26 CN CN200810118865A patent/CN101658521A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103156849A (en) * | 2013-03-21 | 2013-06-19 | 青岛正大海尔制药有限公司 | Compound pseudoephedrine hydrochloride enteric-coated tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8642083B2 (en) | Controlled release complex composition comprising angiotensin-II-receptor blockers and HMG-CoA reductase inhibitors | |
| CN101987091B (en) | Venlafaxine hydrochloride sustained-release pellet capsules | |
| JP2001509157A (en) | Time-specific controlled-release dosage formulation and its preparation | |
| SK285359B6 (en) | Coated cores with delayed release of active substance and pharmaceutical dosage forms comprising thereof | |
| JP2009545560A5 (en) | ||
| US20110111022A1 (en) | Pharmaceutical formulation | |
| WO2021129735A1 (en) | Solid preparation, and preparation method therefor and use thereof | |
| EP2255796A2 (en) | Pharmaceutical preparation | |
| US20110212175A1 (en) | Combination preparation comprising angiotensin-ii-receptor blocker and hmg-coa reductase inhibitor | |
| CN101658507B (en) | Glyceryl guaiacolate and pseudoephedrine compound sustained release preparation | |
| CN105769773A (en) | Loxoprofen sodium sustained-release pellet | |
| CN101756981B (en) | Brufen loratadine pseudoephedrine release preparation and preparation method thereof | |
| WO2007010501A2 (en) | A pharmaceutical composition comprising a combination of beta blocker and an ace inhibitor | |
| CN1994278A (en) | Sustained-release preparation using acetaminopher, desloratadine and pseudo ephedrine sulfat as active ingredients and preparation process thereof | |
| CN1935142A (en) | Slow-release capsule using noinclude, loratadine and pseudoephedrinesulfate as effective component, and its preparing method | |
| CN101658521A (en) | Paracetamol, pseudoephedrine and chlorphenamine compound sustained release preparation | |
| CN101596157A (en) | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan | |
| CN101596158B (en) | Compound slow release preparation of acetyl aminophenol, pseudoephedrine and dextromethorphan | |
| CN109646417A (en) | A kind of Trimetazidine sustained release tablets and preparation method thereof | |
| CN104856971B (en) | A kind of pulse dual-release preparation and the preparation method and application thereof | |
| CN101757001B (en) | Compound slow-release preparation of benorilate, pseudoephedrine and chlorphenamine | |
| CN101596156B (en) | Compound sustained-release preparation for paracetamol and pseudoephedrine | |
| WO2011028016A2 (en) | Pharmaceutical preparation comprising beta-adrenergic blockers and angiotensin ii receptor blockers | |
| CN101756987A (en) | Compound sustained-release preparation of guaiacol olycerin ether, pseudoephedrine and dextromethorphan | |
| CN101766608B (en) | Compound pseudoephedrine hydrochloride slow release preparation and preparing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100303 |