CN101596157A - The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan - Google Patents
The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan Download PDFInfo
- Publication number
- CN101596157A CN101596157A CNA2008101145731A CN200810114573A CN101596157A CN 101596157 A CN101596157 A CN 101596157A CN A2008101145731 A CNA2008101145731 A CN A2008101145731A CN 200810114573 A CN200810114573 A CN 200810114573A CN 101596157 A CN101596157 A CN 101596157A
- Authority
- CN
- China
- Prior art keywords
- acceptable salt
- physiologically acceptable
- slow release
- pseudoephedrine
- release preparation
- 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
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of slow releasing preparation that is active component with pseudoephedrine or its physiologically acceptable salt, chlorphenamine or its physiologically acceptable salt and dextromethorphan or its physiologically acceptable salt, it is characterized in that: described delivery system is made up of the label that drug slow is discharged and/or ball core and coating, a described active component part and/or all be present in label and/or the ball core, the active component remainder is present in the coating.
Description
Technical field
The present invention relates to a kind of slow releasing preparation that is active component with pseudoephedrine or its physiologically acceptable salt, chlorphenamine or its physiologically acceptable salt and dextromethorphan or its physiologically acceptable salt.
Background technology
Common cold, motherland's medical science claims " cold ", is a kind of respiratory tract commonly encountered diseases that is caused by multiple virus, wherein 30%-50% is that rhinovirus by certain serotype causes.Though common cold is mainly in early winter, in any season, as can taking place in spring, summer, the Causative virus of the flu of Various Seasonal is not just the same yet.It is sporadic that the flu case distributes, do not cause popular, the normal bacterial infection that easily merges.The common cold onset is more anxious, and early symptom has pharyngeal dried itching or burning sensation, sneeze, nasal obstruction, watery nasal discharge, with pharyngalgia, and symptoms such as low grade fever, headache.Usually adopt symptomatic treatment, 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.
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.
Dextromethorphan has another name called dextro-methorphan, goes on the market in the U.S. in 1954.Its does not have anesthesia through strict and animal experiment and clinical research widely proves that its curative effect certainly, seldom has side effects, and is the most widely used cough medicine in the world." dextromethorphan is a kind of cough medicine that replaces codeine " thought by The World Health Organization (WHO) in 1989.Dextromethorphan has been widely used abroad clinically because of it has characteristics such as potent, long-acting, safe, now state's pharmacopeia such as existing American and Britain, Japan and Italy are recorded, dextromethorphan is very easily by gastrointestinal absorption, oral 10～the 30min of ordinary tablet begins to play a role, maximum appears in 2h left and right sides blood drug level, and plasma half-life is 2～3h.It by liver metabolism or with original shape and metabolite form from renal excretion, its main metabolites is nor-dextromethorphan.Because the dextromethorphan half-life is short, general dosage is 15～30mg, an administration 3～4 times day by day, and blood concentration fluctuation is bigger, easily causes side effect.During using, it uses its hydrobromate usually.
Pseudoephedrine, chlorphenamine, dextromethorphan are prepared into slow releasing preparation, can overcome the relevant symptom of flu comprehensively, comprise simultaneously symptoms such as obturation with pain and heating, sneeze, dry cough.Because pseudoephedrine, chlorphenamine, dextromethorphan using dosage, rate of release, the difference of aspects such as absorbance need provide a kind of three of making to discharge, absorb and 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 pseudoephedrine or its physiologically acceptable salt, chlorphenamine or its physiologically acceptable salt, dextromethorphan 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, a described active component part and/or all be present in label and/or the ball core, the active component remainder is present in the coating.Described pseudoephedrine or its physiologically acceptable salt, chlorphenamine or its physiologically acceptable salt and dextromethorphan or its physiologically acceptable salt all are slow release and discharge.Described " part ", can be one of in three kinds of active component or two, or one of in three kinds of active component or two or three in a part.Slow releasing preparation of the present invention contains pseudoephedrine or its physiologically acceptable salt 5-180mg in each dosage unit, chlorphenamine or its physiologically acceptable salt 1-36mg, dextromethorphan or its physiologically acceptable salt 15-120mg.As preferably, contain pseudoephedrine or its physiologically acceptable salt 15-150mg in each dosage unit, chlorphenamine or its physiologically acceptable salt 2-24mg, dextromethorphan or its physiologically acceptable salt 15-90mg.
The physiologically acceptable salt of pseudoephedrine of the present invention comprises acylate or inorganic acid salt, wherein is preferably hydrochlorate or sulfate; The physiologically acceptable salt of described chlorphenamine comprises acylate or inorganic acid salt, wherein is preferably maleate.The physiologically acceptable salt of described dextromethorphan comprises acylate or inorganic acid salt, wherein is preferably hydrobromate.
As preferred version of the present invention, the release characteristic of described pseudoephedrine or its physiologically acceptable salt is: 1h (20-65%), 2h (40-85%), 4h (60-90%), 8h (being not less than 70%).
As preferred version of the present invention, the release characteristic of described chlorphenamine or its physiologically acceptable salt is: 1h (30-65%), 2h (40-80%), 4h (60-90%), 8h (being not less than 80%).
As preferred version of the present invention, described dextromethorphan or its physiologically acceptable salt release characteristic are: 1h (15-35%), 2h (30-60%), 4h (45-70%), 8h (being not less than 70%).
Label of the present invention or ball core can be by hydroxypropyl methylcellulose, 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.
Coating material of the present invention, one or more in can being compared by ethyl cellulose, starch, Aquacoat, methylcellulose, cellulose acetate, acrylic resin, Opadry, Su Li are made.
Slow releasing preparation of the present invention as required, can be tablet, granule, pill, capsule, suspensoid etc.
Slow releasing preparation of the present invention as required, can add lubricant, and described lubricant can and month be hung in the pure magnesium sulfate one or more for magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols.
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.
The specific embodiment
By following examples the slow releasing preparation that is active component with pseudoephedrine or its physiologically acceptable salt, chlorphenamine or its physiologically acceptable salt and dextromethorphan 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:
| Pseudoephedrine hydrochloride | 90g |
| Chlorphenamine maleate | 4g |
| Dextromethorphan hydrobromide | 30g |
| Brazil wax | 45g |
| Acrylic resin | 25g |
| Microcrystalline Cellulose | 46g |
| 10% 30 POVIDONE K 30 BP/USP 30Aqueous solution | In right amount |
| Magnesium stearate | In right amount |
The coating prescription:
| Opadry | 10g |
| Pure water | Add to 1000ml |
Make 1000 (sheets)
Preparation method 1:
(1) particulate preparation Brazil wax, acrylic resin, microcrystalline Cellulose are crossed 80 mesh sieves, mix homogeneously respectively.Add pseudoephedrine hydrochloride, chlorphenamine maleate, dextromethorphan hydrobromide 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, acrylic resin 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, acrylic resin, microcrystalline Cellulose and the abundant mix homogeneously of dextromethorphan hydrobromide, 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:
| Pseudoephedrine hydrochloride | 60g |
| Dextromethorphan hydrobromide | 15g |
| Chlorphenamine maleate | 2g |
| Cellulose acetate | 20g |
| Hydroxypropyl methylcellulose E5 | 55g |
| Lactose | 65g |
| 10% 30 POVIDONE K 30 BP/USP 30Aqueous solution | In right amount |
| Pulvis Talci | In right amount |
The coating prescription:
| Chlorphenamine maleate | 2g |
| Opadry II | 10g |
| Pure water | An amount of to dissolving fully |
Make 1000 (sheets)
Preparation method 1:
(1) particulate preparation cellulose acetate, hydroxypropyl methylcellulose E5, lactose, cross 80 mesh sieves respectively,, add pseudoephedrine hydrochloride, dextromethorphan hydrobromide, the chlorphenamine maleate of recipe quantity again with the abundant mixing of equivalent incremental method, make 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) preparation of coating solution adds to chlorphenamine maleate, 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 Pulvis Talci, mix homogeneously, tabletting promptly gets tablet I.
(5) in (1) gained granule, add an amount of Pulvis Talci, 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) cellulose acetate 10g, hydroxypropyl methylcellulose E520g, lactose 35g cross 80 mesh sieves respectively, and mix homogeneously adds pseudoephedrine hydrochloride, the chlorphenamine maleate 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 remaining cellulose acetate in the prescription, hydroxypropyl methylcellulose E5, lactose, dextromethorphan hydrobromide mix homogeneously, standby.
(3) preparation of coating solution adds to chlorphenamine maleate, 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 Pulvis Talci respectively, mix homogeneously, the compacting double-layer tablet promptly gets tablet II.
(6) in (1), (2) gained granule, add an amount of Pulvis Talci 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 | 40g |
| Chlorphenamine maleate | 1g |
| Dextromethorphan hydrobromide | 15g |
| Sodium alginate | 20g |
| Gelatin | 28g |
| Pregelatinized Starch | 50g |
| 10% 30 POVIDONE K 30 BP/USP 25Aqueous solution | In right amount |
The coating prescription:
| Pseudoephedrine sulfate | 5g |
| Chlorphenamine maleate | 1g |
| Cellulose diacetate | 15g |
| Ethanol | An amount of to dissolving fully |
Make 1000 (sheets)
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 dextromethorphan hydrobromide 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 50 ℃ 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 cellulose diacetate, 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 hydrochloride | 90g |
| Chlorphenamine maleate | 4.0 |
| Dextromethorphan hydrobromide | 30g |
| 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 90 | In right amount |
| Water | In right amount |
| Dehydrated alcohol | In right amount |
The coating prescription:
| Opadry | 30g |
| Pure water | Add to 1000ml |
Make 1000 (sheets)
Preparation method:
(1) pseudoephedrine hydrochloride slow release micropill
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 hydrochloride 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 hydrochloride micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again.
Promptly get pseudoephedrine hydrochloride 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) dextromethorphan hydrobromide sustained-release micropill preparation
I, an amount of 30 POVIDONE K 30 BP/USP 30 is added an amount of dehydrated alcohol be made into 5% (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 dextromethorphan hydrobromide, treats that dextromethorphan hydrobromide 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 dextromethorphan hydrobromide sustained-release micropill, 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 hydrochloride | 90g |
| Chlorphenamine maleate | 4g |
| Dextromethorphan hydrobromide | 30g |
| 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 coating prescription:
| Opadry II | 25g |
| Pure water | Add to 1000ml |
Make 1000 (sheets)
Preparation method:
(1) the plain sheet preparation of dextromethorphan hydrobromide sustained-release
It is evenly mixed to get the hydroxypropyl emthylcellulose E4MP, dextromethorphan hydrobromide, 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 hydrochloride slow release micropill
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 hydrochloride 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 hydrochloride micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again.
Promptly get pseudoephedrine hydrochloride 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
Embodiment 6
Prescription:
| Pseudoephedrine hydrochloride | 90g |
| Chlorphenamine maleate | 2g |
| Dextromethorphan hydrobromide | 30g |
| Celphere | 100g |
| Hydroxypropyl methylcellulose E5 | 5g |
| Hydroxypropyl methylcellulose E4MP | 40g |
| Brazil wax | 15g |
| The Sulisi solid content | 30g |
| The water solublity coating powder | 5g |
| Titanium dioxide | 1g |
| Lactose | 80g |
| 30 POVIDONE K 30 BP/USP 15 | In right amount |
| Water | In right amount |
| Dehydrated alcohol | 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 dextromethorphan hydrobromide sustained-release
It is evenly mixed to get the hydroxypropyl emthylcellulose E4MP, dextromethorphan hydrobromide, 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 hydrochloride slow release micropill
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 hydrochloride 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 hydrochloride micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again.
Promptly get pseudoephedrine hydrochloride medicine-feeding micropill, standby.
(3) chlorphenamine maleate slow releasing tablet
I, chlorphenamine maleate is joined 10% 30 POVIDONE K 30 BP/USP
15In the aqueous solution, as binding agent, standby II, Brazil wax, lactose are crossed 100 mesh sieves respectively, and mix homogeneously adds binding agent system soft material, 20 mesh sieve system wet granulars, and 50 ℃ of dryings, 20 mesh sieve granulate add magnesium stearate, tabletting.
Promptly get the chlorphenamine maleate slow releasing tablet, standby.
(4) Opadry is added in the pure water, and add pure water, stirred 1 hour to 100ml.
(5) get (2) gained micropill and add an amount of magnesium stearate, mix homogeneously, tabletting with (1) and (3) tabletting, is put the plain sheet that makes to coating pan again, air blast is heated to about 50 ℃, at the uniform velocity spray into the coating solution coating, the limit sprays into the heating of coating solution snare drum wind, makes plain sheet temperature remain on 45-50 ℃, until evenly wrapping the thin film clothing, be drying to obtain.
(6) the plain sheet that (1) is made is put to coating pan, and air blast is heated to about 50 ℃, at the uniform velocity sprays into the coating solution coating, and the limit sprays into the heating of coating solution snare drum wind, makes plain sheet temperature remain on 45-50 ℃, until evenly wrapping the thin film clothing, is drying to obtain.
(7) get the plain sheet of (6), (2), (3) gained, coated tablet, micropill and fill in the hungry area softgel shell, promptly get capsule I.
(8) get (2) gained micropill and add an amount of magnesium stearate, mix homogeneously, tabletting;
(9) slow releasing tablet of (1), (3), (8) gained is put into high-efficiency coating machine respectively, be heated to about 60 ℃, at the uniform velocity spray into the coating solution coating, make plain sheet temperature remain on 50-55 ℃,, be drying to obtain until evenly wrapping the thin film clothing.Obtain three kinds of sustained release coating sheets respectively, above-mentioned three kinds of sustained release coating sheets are packed in the capsule, promptly get capsule II.
The release characteristic of active component is as shown in table 6 in the gained different dosage form.
The release characteristic of active component in table 6 different dosage form
Claims (14)
1, a kind of compound slow release preparation that is active component with pseudoephedrine or its physiologically acceptable salt, chlorphenamine or its physiologically acceptable salt and dextromethorphan 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 coating, a described active component part and/or all be present in label and/or the ball core, the active component remainder is present in the coating.
2, compound slow release preparation according to claim 1 is characterized in that: pseudoephedrine or its physiologically acceptable salt, chlorphenamine or its physiologically acceptable salt and dextromethorphan 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 pseudoephedrine or its physiologically acceptable salt 5-180mg in each dosage unit, chlorphenamine or its physiologically acceptable salt 1-36mg, dextromethorphan or its physiologically acceptable salt 15-120mg.
4, compound slow release preparation according to claim 3, it is characterized in that: contain pseudoephedrine or its physiologically acceptable salt 15-150mg in each dosage unit, chlorphenamine or its physiologically acceptable salt 2-24mg, dextromethorphan or its physiologically acceptable salt 15-90mg.
5, according to the described compound slow release preparation of claim 1-4, it is characterized in that: the physiologically acceptable salt of described pseudoephedrine is pseudoephedrine hydrochlorate or pseudoephedrine sulfate.
6, according to the described compound slow release preparation of claim 1-4, it is characterized in that: the physiologically acceptable salt of described chlorphenamine is the chlorphenamine maleate.
7, according to the described compound slow release preparation of claim 1-4, it is characterized in that: the physiologically acceptable salt of described dextromethorphan is dextromethmorphan hydrobromide.
8, 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, acrylic resin, microcrystalline Cellulose, pregelatinized Starch, in the titanium dioxide one or more are made.
9, according to the described compound slow release preparation of claim 1-4, it is characterized in that: one or more during described coating is compared by ethyl cellulose, starch, Aquacoat, methylcellulose, cellulose acetate, acrylic resin, Opadry, Su Li are made.
10, according to the described compound slow release preparation of claim 1-4, it is characterized in that: the release characteristic of pseudoephedrine or its physiologically acceptable salt is: 1h:20-65%, 2h:40-85%, 4h:60-90%, 8h: be not less than 80%.
11, according to the described compound slow release preparation of claim 1-4, it is characterized in that: 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%.
12, according to the described compound slow release preparation of claim 1-4, it is characterized in that: the release characteristic of dextromethorphan or its physiologically acceptable salt is: 1h:15-35%, 2h:30-60%, 4h:45-70%, 8h: be not less than 70%.
13, according to the described compound slow release preparation of claim 1-4, it is characterized in that: described preparation is tablet, granule, pill, capsule or suspensoid.
14, according to the described compound slow release preparation of claim 1-4, be characterised in that: described preparation 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101145731A CN101596157A (en) | 2008-06-04 | 2008-06-04 | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101145731A CN101596157A (en) | 2008-06-04 | 2008-06-04 | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101596157A true CN101596157A (en) | 2009-12-09 |
Family
ID=41417877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008101145731A Pending CN101596157A (en) | 2008-06-04 | 2008-06-04 | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101596157A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102018712A (en) * | 2010-12-30 | 2011-04-20 | 东莞广州中医药大学中医药数理工程研究院 | Pharmaceutical composition comprising dextromethorphan, chlorpheniramine and pseudoephedrine and preparation method thereof |
| CN103169705A (en) * | 2011-12-23 | 2013-06-26 | 重庆医药工业研究院有限责任公司 | Compound orally disintegrating tablet containing chlorpheniramine and dextromethorphan |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1360892A (en) * | 2000-12-28 | 2002-07-31 | 营口奥达制药有限公司 | Dry mixed suspension of Meptin and pseudoephe and its prepn |
| CN1476898A (en) * | 2002-08-23 | 2004-02-25 | 涛 吴 | Compound skeleton tablet capable of prolonging release after oral administrationi for curing common cold |
| CN1535686A (en) * | 2003-04-09 | 2004-10-13 | 北京德众万全药物技术开发有限公司 | Slowly-released preparation containing loratadine and pseudoephedrine sulfate and its preparation method |
| CN1634059A (en) * | 2004-10-11 | 2005-07-06 | 贵阳云岩西创药物科技开发有限公司 | Pseudoephedrine hydrochloride, dextromethorphan hydrobromide and chlorphenamine maleates gel formulation and its preparing process |
| CN1634060A (en) * | 2004-10-11 | 2005-07-06 | 贵阳云岩西创药物科技开发有限公司 | Gelatin formulation of dextromethorphan hydrobromide and its preparing method |
| CN1679525A (en) * | 2005-01-12 | 2005-10-12 | 复旦大学 | Oral disintegrant of compound paracetamol |
| CN1830442A (en) * | 2006-04-03 | 2006-09-13 | 深圳市制药厂 | Compound formula dextro methaphen oral disintegration tablet and its preparation method |
| CN101002755A (en) * | 2007-01-10 | 2007-07-25 | 复旦大学 | Compounding and pulsation-releasing preparation, and its preparing method |
-
2008
- 2008-06-04 CN CNA2008101145731A patent/CN101596157A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1360892A (en) * | 2000-12-28 | 2002-07-31 | 营口奥达制药有限公司 | Dry mixed suspension of Meptin and pseudoephe and its prepn |
| CN1476898A (en) * | 2002-08-23 | 2004-02-25 | 涛 吴 | Compound skeleton tablet capable of prolonging release after oral administrationi for curing common cold |
| CN1535686A (en) * | 2003-04-09 | 2004-10-13 | 北京德众万全药物技术开发有限公司 | Slowly-released preparation containing loratadine and pseudoephedrine sulfate and its preparation method |
| CN1634059A (en) * | 2004-10-11 | 2005-07-06 | 贵阳云岩西创药物科技开发有限公司 | Pseudoephedrine hydrochloride, dextromethorphan hydrobromide and chlorphenamine maleates gel formulation and its preparing process |
| CN1634060A (en) * | 2004-10-11 | 2005-07-06 | 贵阳云岩西创药物科技开发有限公司 | Gelatin formulation of dextromethorphan hydrobromide and its preparing method |
| CN1679525A (en) * | 2005-01-12 | 2005-10-12 | 复旦大学 | Oral disintegrant of compound paracetamol |
| CN1830442A (en) * | 2006-04-03 | 2006-09-13 | 深圳市制药厂 | Compound formula dextro methaphen oral disintegration tablet and its preparation method |
| CN101002755A (en) * | 2007-01-10 | 2007-07-25 | 复旦大学 | Compounding and pulsation-releasing preparation, and its preparing method |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102018712A (en) * | 2010-12-30 | 2011-04-20 | 东莞广州中医药大学中医药数理工程研究院 | Pharmaceutical composition comprising dextromethorphan, chlorpheniramine and pseudoephedrine and preparation method thereof |
| CN103169705A (en) * | 2011-12-23 | 2013-06-26 | 重庆医药工业研究院有限责任公司 | Compound orally disintegrating tablet containing chlorpheniramine and dextromethorphan |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101987091B (en) | Venlafaxine hydrochloride sustained-release pellet capsules | |
| WO2011063732A1 (en) | Paliperidone double-layered osmotic pump controlled release tablet and preparation method thereof | |
| CN103417505A (en) | Huperzine A controlled release preparation having biphasic release behavior, and preparation method thereof | |
| CN103860504A (en) | Slow/controlled-release preparation of ticagrelor | |
| CN102335155B (en) | Quetiapine fumarate sustained-release tablets and preparation method thereof | |
| CN101780049A (en) | Enteric solid preparation using feinuobeite acid and feinuobeite salt as major ingredients and preparation method thereof | |
| CN101596157A (en) | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan | |
| CN101756981B (en) | Brufen loratadine pseudoephedrine release preparation and preparation method thereof | |
| CN101658507B (en) | Glyceryl guaiacolate and pseudoephedrine compound sustained release preparation | |
| CN1935142A (en) | Slow-release capsule using noinclude, loratadine and pseudoephedrinesulfate as effective component, and its preparing method | |
| CN109646417A (en) | A kind of Trimetazidine sustained release tablets and preparation method thereof | |
| CN1994278A (en) | Sustained-release preparation using acetaminopher, desloratadine and pseudo ephedrine sulfat as active ingredients and preparation process thereof | |
| CN101849942B (en) | Medicinal composition for treating hypertension | |
| CN104856971B (en) | A kind of pulse dual-release preparation and the preparation method and application thereof | |
| CN101584683A (en) | Metolazone slow-release capsule and method for preparing same | |
| CN101185624A (en) | Novel composing prescription sustained-release preparation for treating high blood pressure and preparation method thereof | |
| CN101214379A (en) | Novel composing prescription sustained-release preparation for treating high blood pressure and preparation method thereof | |
| CN101596158B (en) | Compound slow release preparation of acetyl aminophenol, pseudoephedrine and dextromethorphan | |
| CN101773482B (en) | Three-stage pulsed release controlled release tablet and preparation method thereof | |
| CN101756987A (en) | Compound sustained-release preparation of guaiacol olycerin ether, pseudoephedrine and dextromethorphan | |
| CN101416966A (en) | Medical composition capable of treating hypertension | |
| CN101658521A (en) | Paracetamol, pseudoephedrine and chlorphenamine compound sustained release preparation | |
| WO2011028016A2 (en) | Pharmaceutical preparation comprising beta-adrenergic blockers and angiotensin ii receptor blockers | |
| CN114533744A (en) | Ticagrelor-aspirin compound pellet preparation and preparation method thereof | |
| CN101757001B (en) | Compound slow-release preparation of benorilate, pseudoephedrine and chlorphenamine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 100083 Haidian District, Xueyuan Road, No. 30, A building, room No. 15, room, room 15 Applicant after: Beijing Kexin Bicheng Medicine Science & Technology Developing Co., Ltd. Address before: 100190, room 1410, satellite building, No. 63, Zhichun Road, Beijing, Haidian District Applicant before: Beijing Kexin Bicheng Medicine Science & Technology Developing Co., Ltd. |
|
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20091209 |