CN101700245B - Compound drug for curing colds and preparation technology thereof - Google Patents
Compound drug for curing colds and preparation technology thereof Download PDFInfo
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- CN101700245B CN101700245B CN2009101910728A CN200910191072A CN101700245B CN 101700245 B CN101700245 B CN 101700245B CN 2009101910728 A CN2009101910728 A CN 2009101910728A CN 200910191072 A CN200910191072 A CN 200910191072A CN 101700245 B CN101700245 B CN 101700245B
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Abstract
The invention relates to a compound drug for curing colds and a preparation technology thereof. The compound drug consists of active components of Ibuprofen, pseudoephedrinehydrochloride, chlorphenamine maleate with effective doses and proper amount of pharmaceutic adjuvants, which is characterized by preparing lbuprofen with a partial effective dose and pseudoephedrinehydrochloride with an effective dose into a sustained-release preparation; preparing ibuprofen with a residual effective dose and chlorphenamine maleate with an effective dose into an immediate-release preparation; and preparing the sustained-release preparation and the immediate-release preparation into various drug preparations according to conventional methods. The invention adopts the sustained-release technology and the immediate-release technology, effectively controls absorption and use of the three different drug active components in vivo, enables the blood concentration of the three drug active components to achieve effective curative concentration and coincidence in decreasing time, thus enhancing the pesticide effect of the compound drug in the invention cooperatively and improving bioavailability of the compound drug in the invention.
Description
Technical field
The present invention relates to a kind of compound medicine and preparation technology thereof who treats flu.
Background technology
Ibuprofen is effective PGSI, has analgesic, analgesia and antiinflammatory action; Almost insoluble in water, in sodium hydroxide or sodium carbonate test solution, be prone to dissolve.Oral easy absorption, per rectum absorbs after the medication, and Tmax (expression reaches the used time of peak value from the back of taking medicine to blood drug level) is about 0.92 ± 0.33h, and during consumption 200mg, blood drug level is 22 μ g/ml～27 μ g/ml; During consumption 400mg 23 μ g/ml～45 μ g/ml; During consumption 600mg 43 μ g/ml～57 μ g/ml.Half-life T behind the single administration
1/2Be generally 1.82h.
Pseudoephedrine hydrochloride has optionally vasoconstrictive effect, eliminates nasopharynx part mucous hyperemia, swelling, alleviates symptoms such as nasal obstruction; Very easily dissolving in water, oral post-absorption is fast, and Tmax is about 1h; 0.5 average blood drug level is 274 ± 33 μ g/ml between the～2h, mean half-life (T
1/2) be 4.35h.
The collaborative alleviation of chlorphenamine maleate nasal mucosa is congested, and certain drowsiness and anticholinergic side effects is arranged, and in water, is prone to dissolve, and oral slower through gastrointestinal absorption, bioavailability is about 25%～50%, the 15～60min onset of oral back, and Tmax is 3～6h, half-life (T
1/2) be 12～15h.
In treatment flu process, more than three kinds of medicines one work and can alleviate cold symptoms from different perspectives, especially can alleviate the various symptoms such as headache, heating, nasal obstruction, extremities aching pain and laryngopharynx swelling and pain that flu causes simultaneously.But because above three kinds of medicines absorption, half-life separately is different; Make three's plasma concentration curve differ bigger; Can not reach treatment concentration and keep certain hour simultaneously in the identical or close time, thus above three kinds of medicines respectively simultaneously, with every day same number take, possibly cause that then the medicine of long half time can not in time be eliminated; Thereby accumulation causes the generation of some side effect in vivo; Half-life, short medicine then can not be kept effective blood drug concentration, did not reach therapeutic effect.
The compound medicine that comprises above three kinds of active constituents of medicine at present goes on the market in the U.S.; It is the ordinary preparation that adopts conventional traditional preparation process to make; This compound medicine was taken three times in one day, and it is more to take number of times, and it is same owing to these three kinds of each self-absorptions of medicine, half-life difference; Each active constituents of medicine discharges unbalanced, and drug effect is undesirable.
Summary of the invention
The object of the present invention is to provide the ideal compound medicine of a kind of treatment flu drug effect, it comprises ibuprofen, pseudoephedrine hydrochloride and chlorphenamine maleate various active component.Each active constituents of medicine discharges balanced in this compound medicine.
Another object of the present invention is to provide the method for preparing of above-mentioned compound medicine.
The objective of the invention is to realize like this: a kind of compound medicine of treating flu; It comprises ibuprofen, pseudoephedrine hydrochloride and the chlorphenamine maleate active component of effective dose; And an amount of pharmaceutic adjuvant, it is characterized in that: the ibuprofen of part effective dose and the pseudoephedrine hydrochloride of effective dose are processed slow releasing preparation; The ibuprofen of part effective dose and the chlorphenamine maleate of effective dose are processed quick releasing formulation; Again slow releasing preparation and quick releasing formulation are processed various pharmaceutical preparatioies by routine.
Above-mentioned medicament refers to tablet or capsule.
Above-mentioned pharmaceutic adjuvant comprises hydroxypropyl emthylcellulose, polyethylene glycol 6000, Tween 80, cross-linked pvp and lactose; Wherein 60%～90% of the effective dose ibuprofen adopt the adjuvant hydroxypropyl emthylcellulose to process slow releasing preparation with the pseudoephedrine hydrochloride of effective dose; The ibuprofen of surplus and the chlorphenamine maleate of effective dose adopt polyethylene glycol 6000, Tween 80, cross-linked pvp and lactose to process quick releasing formulation.Certainly, the pharmaceutic adjuvant among the present invention can also comprise the lubricant of convention amount, like magnesium stearate or silicon dioxide.
Above-mentioned slow releasing preparation is preferably processed the gastric floating slow-release granular preparation: ibuprofen, pseudoephedrine hydrochloride and hydroxypropyl emthylcellulose pulverize separately are sieved, put in the boiling granulating machine fluid bed, mix homogeneously is heated to 60～80 ℃; Hydroxypropyl emthylcellulose is dissolved in is configured to Gonak in the alcoholic solution,, promptly get with Gonak spray granulation, drying.
Above-mentioned quick releasing formulation is preferably processed solid dispersion immediate-release granules preparation: with chlorphenamine maleate and polyethylene glycol 6000 mix homogeneously; Pulverize with the micropowder pulverizer; Add Tween 80 solution, mix homogeneously is put grinding in ball grinder with mixture and is prepared solid dispersion; Solid dispersion is added the ibuprofen of cross-linked pvp, lactose and surplus, granulate with alcoholic solution, drying makes.
Another object of the present invention is achieved in that a kind of method for preparing of treating the compound medicine of flu, it is characterized in that: it comprises ibuprofen, pseudoephedrine hydrochloride and the chlorphenamine maleate active component of effective dose, and an amount of pharmaceutic adjuvant; And comprise the steps to make: the ibuprofen of part effective dose and the pseudoephedrine hydrochloride of effective dose are processed slow releasing preparation; The ibuprofen of part effective dose and the chlorphenamine maleate of effective dose are processed quick releasing formulation; Again slow releasing preparation and quick releasing formulation are processed various pharmaceutical preparatioies by routine.
Above-mentioned compound medicine is processed the concrete method for preparing of tablet:
A. the particulate preparation of gastric floating slow-release:
The effective dose ibuprofen that with percentage by weight is 60%～90%, the pseudoephedrine hydrochloride of effective dose and 99.5%～99.95% pulverize separately of an amount of hydroxypropyl emthylcellulose cross 80～200 mesh sieves (preferred 100 orders); Put in the boiling granulating machine fluid bed; Mix homogeneously; Be heated to 60～80 ℃; Again the hydroxypropyl emthylcellulose of remainder being dissolved in percentage by volume is to be configured to the Gonak that mass percent is 0.5%～2% (preferred 1%) in 40%～60% the alcoholic solution (preferred 50%), with this Gonak spray granulation, stops spraying when better to shaping particles; Dry 20～40 minutes, promptly get the gastric floating slow-release granule;
B. the preparation of solid dispersion immediate-release granules:
With the chlorphenamine maleate of effective dose and an amount of polyethylene glycol 6000 mix homogeneously; Pulverize with the micropowder pulverizer, powder particle diameter reaches more than 200 orders, adds the Tween 80 aqueous solution; Mix homogeneously is with the powerful preparation solid dispersion that grinds in the mixture Place grinding machine; With the ibuprofen, cross-linked pvp and the lactose that add surplus in the gained solid dispersion, the use percentage by volume is 60～80% alcoholic solution granulation, and 40 ℃ are dried to substantially anhydrous branch, process immediate-release granules;
C. above-mentioned slow-releasing granules that makes and immediate-release granules are added lubricant respectively, use the bi-layer tablet press tabletting, slow-releasing granules is pressed into inner layer piece, and immediate-release granules is pressed into outer-skin sheet, makes compound medicine tablet according to the invention.
Compound medicine according to the invention is processed the concrete method for preparing of capsule:
A. the preparation of slow-releasing granules:
With the effective dose ibuprofen 60%～90%, 99.5%～99.95% pulverize separately of the pseudoephedrine hydrochloride of effective dose and an amount of hydroxypropyl emthylcellulose crosses 80～200 mesh sieves; With efficient wet granulator mix homogeneously; Again the hydroxypropyl emthylcellulose of surplus being dissolved in percentage by volume is that to be configured to mass percent in 40%～60% the alcoholic solution be 0.5%～2% Gonak; Adding this Gonak granulates at a high speed; Oven dry gets slow-releasing granules;
B. the preparation of solid dispersion immediate-release granules:
Chlorphenamine maleate and polyethylene glycol 6000 mix homogeneously with effective dose; Pulverize with the micropowder pulverizer, powder particle diameter reaches more than 200 orders, adds the Tween 80 aqueous solution then; Mix homogeneously is with the powerful preparation solid dispersion that grinds in the mixture Place grinding machine; The solid dispersion of gained is added the ibuprofen and the cross-linked pvp of surplus, and using percentage by volume is that 60～80% alcoholic solution is granulated, and 40 ℃ are dried to substantially anhydrous branch, process immediate-release granules;
C. above-mentioned slow-releasing granules and immediate-release granules are mixed, add lubricant, mix homogeneously makes capsule by routine.
Certainly, medicine of the present invention can also utilize conventional sustained-release preparation technology and quick releasing formulation preparation technology to process except that tablet, arbitrary peroral dosage form the capsule.
The concrete proportioning of medicine each component according to the invention: in weight portion, 100 parts of ibuprofen, 10～20 parts of pseudoephedrine hydrochlorides, 1～2 part of chlorphenamine maleate, 5～20 parts of hydroxypropyl emthylcelluloses, 1～2 part of polyethylene glycol 6000,10～40 parts of cross-linked pvps, 10～40 parts of lactose, 0.01～0.09 part of 0.04～0.06g/ml Tween 80 aqueous solution, 1～3 part of lubricant.
The characteristic that the present invention is short according to the ibuprofen peak time, the half-life is short, be insoluble in water is processed slow releasing preparation with the part ibuprofen and is prolonged peak time; Pseudoephedrine hydrochloride very easily is dissolved in water, and peak time is short, the half-life is shorter, thus process slow releasing preparation together with the part ibuprofen, thus prolong peak time; Chlorphenamine maleate is soluble in water, but slow in gastrointestinal absorption, and peak time is long, long half time, and the present invention is made into quick releasing formulation to shorten peak time.The present invention reaches effective treatment concentration and the time of disappearing with this blood drug level of controlling three kinds of different activities compositions, the collaborative drug effect that strengthens compound medicine of the present invention.
The present invention processes the intragastric floating slowly releasing preparation with ibuprofen and pseudoephedrine hydrochloride.The intragastric floating slowly releasing preparation that ibuprofen and pseudoephedrine hydrochloride are made is processed according to the fluid dynamic equilibrium principle, and is different with general slow release formulation, swims on the gastric content after this dosage form is oral, not influenced by gastric emptying in the holdup time of gastric.When system swam on the gastric content, medicine slowly discharged from system with the speed of expection, and after drug release finished, the system remnant was discharged from stomach; The preparation density of processing is lower than the density 1mg/ml of gastric juice, and medicine is prolonged at gastric transit time, and reaches buoyant purpose at gastric.Again since the absorption window of ibuprofen in the characteristic of rectum; Simultaneously also play antipyretic effect fast for compound medicine of the present invention; The present invention adopts the 60%-90% of ibuprofen total amount and pseudoephedrine hydrochloride to process slow releasing preparation, and the ibuprofen and the chlorphenamine maleate of surplus are processed quick releasing formulation.After in the compound medicine entering body of the present invention, the rapid release of immediate-release granules plays a role, and slow-released part forms the showy sheet of stomach then, floats on the slow balance that discharges in gastric juice surface and plays a role.
Compound medicine of the present invention mainly is applicable to extenuates the symptom that causes because of pollinosis, other upper respiratory tract allergy and common cold, as headache, nasal congestion, sneeze, hydrophthalmia, rhinorrhea, pruritus, hole press, symptoms such as pain and the pain of injury, fever.But its administered through oral administration, an a slice, each a slice of morning and evening, every 0.3 gram～0.4 gram.
Compound medicine according to the invention has following beneficial effect:
1, the present invention adopts showy sheet slow release method of stomach and dispersible tablet rapid release technology; Controlled the utilization of three kinds of different pharmaceutical active component absorption in vivo effectively; It is consistent with the time of disappearing to make the blood drug level of these three kinds of active constituents of medicine reach effective treatment concentration; Thereby work in coordination with the drug effect that has strengthened compound medicine of the present invention, improved the bioavailability of compound medicine of the present invention.
2, compound medicine taking convenience of the present invention, the effective blood drug concentration of taking medicine and once can keep 12 hours, only take twice every day, and sooner or later respectively once, taking convenience reduces the rate that misses, and improves the patient doctor from property.
3, pseudoephedrine hydrochloride has pressor effect; When its blood drug level is higher, let hypertensive patient's hypertension easily, and the present invention adopts the stomach sheet slow release method of floating, and steadily discharges pseudoephedrine hydrochloride; Can bring into play and shrink the nose blood vessel function; Be unlikely to again because of excessive concentration can cause hypertension, reduce side effect, better bring into play curative effect.
4, the compound medicine that utilizes the method for the invention to prepare can reduce the fluctuation range of medicine blood drug level, makes poisonous side effect of medicine according to the invention little.
In order further to prove the drug effect of medicine according to the invention, the inventor has done following evidence.
Compound medicine of the present invention is to the influence test of anesthetized dog cardiovascular and respiratory system
15 of hybrid dogs, male and female half and half, body weight are 9.2～11.0kg, are divided into 3 groups (0.5% carboxymethyl cellulose sodium matched group, low, high dose compound medicine administration of the present invention groups) at random by body weight.Animal with pentobarbital sodium anesthesia (30mg/kg, iv) after, separate common carotid artery and trachea; Carry out common carotid artery and tracheal intubation respectively; With MS-302 multimedia bio signal recording system monitoring blood pressure, breathing and II lead electrocardiogram, stablize behind the 60min administration group and give compound medicine 5.8mg/kg of the present invention from duodenum and (be equivalent to ibuprofen 5mg/kg, pseudoephedrine hydrochloride 0.75mg/kg; Chlorphenamine maleate 0.05mg/kg), 23.2mg/kg (is equivalent to ibuprofen 20mg/kg; Pseudoephedrine hydrochloride 3mg/kg, chlorphenamine maleate 0.2mg/kg), the administration volume is 1mg/kg.Matched group gives isopyknic 0.5% sodium carboxymethyl cellulose.
Result: after 12 fat intestinal give compound medicine 5.8mg/kg of the present invention (be equivalent to clinical single approximately by body surface area calculating and intend 1 times with dosage); Blood pressure, breathing (frequency and the degree of depth) and electrocardiogram to anesthetized dog in the 4h do not have obvious influence, relatively do not have significant difference (P＞0.05) with matched group.After duodenum gave compound medicinal formulation 23.2mg/kg of the present invention (calculate to be equivalent to clinical single approximately and to intend 4 times with dosage by body surface area), interior breathing (frequency and the degree of depth) and the electrocardiogram to anesthetized dog of 4h do not have obvious influence, and compared no significant difference; Blood pressure is on the rise in the 4h, but relatively and with matched group does not more all have statistics marked difference (P＞0.05) before and after self
The compound recipe cold medicine preparation of gained of the present invention is taken in the experimental result explanation, because blood drug level is steady, takes the rising that can not cause blood pressure by clinical dosage, and other side effect.
Compound medicine of the present invention is carried out acute toxicity test research
(1) acute toxicity test in mice
Experimentation mouse stomach give the acute toxicity test of compound medicine of the present invention (ibuprofen: pseudoephedrine hydrochloride: the chlorphenamine maleate weight part ratio is 100: 15: 1).After the observation mouse stomach gives compound medicine of the present invention, acute toxic reaction that is produced and death condition.Measure median lethal dose(LD 50) LD
50Value is for clinical practice provides the safety foundation.The result shows: mouse stomach gives compound medicine LD of the present invention
50Be 4726.1mg/kg, 95% credible be 3927.7～5686.7mg/kg.
(2) rat acute toxicity test
Experimentation rat oral gavage give the acute toxicity test of compound medicine of the present invention (ibuprofen: pseudoephedrine hydrochloride: the chlorphenamine maleate weight part ratio is 100: 15: 1).The result shows: it is 4400.5mg/kg that rat oral gavage gives compound medicine LD50 of the present invention, 95% the credible 3707.0～5223.7mg/kg that is limited to.
Pharmaceutical preparation safety of the present invention is taken in the experimental result explanation, toxic and side effects is little, can not cause acute toxicity.
The specific embodiment
Below in conjunction with embodiment the present invention is further described, but the present invention is not limited to this.
Embodiment 1
A kind of compound medicine of treating flu; It comprises following component: in weight portion, and the Tween 80 aqueous solution 0.05g of ibuprofen 200g, pseudoephedrine hydrochloride 30g, chlorphenamine maleate 2g, hydroxypropyl emthylcellulose 30g, polyethylene glycol 6000 3g, cross-linked pvp 50g, lactose 70g, 0.04～0.06g/ml and magnesium stearate 5g; Process tablet by following step:
A. get ibuprofen powder 170g, above-mentioned pseudoephedrine hydrochloride powder is crossed 100 mesh sieves, gets hydroxypropyl emthylcellulose powder 29.85g; Put in the boiling granulating machine fluid bed; Mix homogeneously is heated to 60～80 ℃, and it is that to be configured to mass percent in 50% the alcoholic solution be 1% Gonak that the hydroxypropyl emthylcellulose of surplus is dissolved in percentage by volume; Add this 1% Gonak and granulate at a high speed, stop spraying to shaping particles when better; Dry 20～40 minutes, promptly get the gastric floating slow-release granule;
B. with above-mentioned chlorphenamine maleate and polyethylene glycol 6000 mix homogeneously; Pulverize with the micropowder pulverizer, powder particle diameter reaches more than 200 orders, adds above-mentioned Tween 80 aqueous solution then; Mix homogeneously prepares solid dispersion with powerful grinding the in the mixture Place grinding machine; With the gained solid dispersion add surplus ibuprofen powder, cross-linked pvp, lactose, granulate (can add an amount of pigment and slow release layer distinguishes) with 60～80% alcoholic solution, 40 ℃ are dried to substantially anhydrous branch, process immediate-release granules;
C. above-mentioned gastric floating slow-release granule that makes and immediate-release granules are added magnesium stearate lubricant respectively, use the bi-layer tablet press tabletting, slow-releasing granules is pressed and is inner layer piece, and immediate-release granules is pressed into outer-skin sheet, processes 1000 tablets of compound medicine tablets of the present invention.
Embodiment 2-9 utilizes different prescription components, according to the preparation technology of embodiment 1, makes compound medicine tablet of the present invention, and following unit is: gram.
| The component name | Ibuprofen | Pseudoephedrine hydrochloride | Chlorphenamine maleate | Hydroxypropyl emthylcellulose | Polyethylene glycol 6000 | Cross-linked pvp | Lactose | 0.04 the Tween 80 aqueous solution of～0.06g/ml | Lubricant |
| 2 | 300 (steps A consumptions 180) | 30 | 3 | 15 (obtain solution consumptions 0.06) | 3 | 30 | 30 | 0.03 | Silicon dioxide 3 |
| 3 | 100 (steps A consumptions 90) | 20 | 2 | 20 (obtain solution consumptions 0.1) | 2 | 40 | 40 | 0.09 | Do not have |
| 4 | 200 (steps A consumptions 150) | 30 | 3 | 25 (obtain solution consumptions 0.07) | 3 | 50 | 50 | 0.1 | Magnesium stearate 2 |
| 5 | 150 (steps A consumptions 90) | 15 | 1.5 | (7.5 obtain solution consumption 0.02) | 1.5 | 15 | 15 | 0.015 | Silica 1 .5 |
| 6 | 1000 (steps A consumptions 900) | 200 | 20 | 200 (obtain solution consumptions 0.2) | 20 | 400 | 400 | 0.9 | Magnesium stearate 30 |
| 7 | 5000 (steps A consumptions 3750) | 750 | 70 | 625 (obtain solution consumptions 1.25) | 75 | 1200 | 1250 | 2.5 | Do not have |
| 8 | 800 (steps A consumptions 560) | 80 | 9 | 45 (obtain solution consumptions 0.14) | 10 | 200 | 310 | 0.5 | Silica 11 |
| 9 | 500 (steps A consumptions 420) | 88 | 7 | 65 (obtain solution consumptions 0.07) | 7.5 | 130 | 190 | 0.39 | Magnesium stearate 13 |
Embodiment 10
A kind of compound medicine of treating flu; It comprises following component: in weight portion, and the Tween 80 aqueous solution 0.03g of ibuprofen 100g, pseudoephedrine hydrochloride 17g, chlorphenamine maleate 1.5g, hydroxypropyl emthylcellulose 19g, polyethylene glycol 6000 1.8g, cross-linked pvp 35g, 0.04～0.06g/ml and silicon dioxide 2.8g; Process capsule by following step:
A. the hydroxypropyl emthylcellulose pulverize separately of 80g ibuprofen, pseudoephedrine hydrochloride and 99.95g is crossed 100 mesh sieves; With efficient wet granulator mix homogeneously; It is that to be configured to mass percent in 50% the alcoholic solution be 1% Gonak that the hydroxypropyl emthylcellulose of 0.05g is dissolved in percentage by volume; Add this 1% Gonak and granulate at a high speed, oven dry gets slow-releasing granules;
B. with chlorphenamine maleate and polyethylene glycol 6000 mix homogeneously, pulverize with the micropowder pulverizer, powder particle diameter reaches more than 200 orders, adds above-mentioned Tween 80 aqueous solution then, and mix homogeneously is with the powerful preparation solid dispersion that grinds in the mixture Place grinding machine; With the ibuprofen and the cross-linked pvp of gained solid dispersion adding surplus, the use percentage by volume is 60～80% alcoholic solution granulation, and 40 ℃ are dried to substantially anhydrous branch, process immediate-release granules;
C. above-mentioned slow-releasing granules and immediate-release granules are mixed, add lubricant silicon dioxide, mix homogeneously, Autocapsulefillingmachine fill capsule makes compound medicine capsule of the present invention.
Claims (3)
1. compound medicine of treating flu; It comprises ibuprofen, pseudoephedrine hydrochloride and the chlorphenamine maleate active component of effective dose; And an amount of pharmaceutic adjuvant, it is characterized in that: the ibuprofen of part effective dose and the pseudoephedrine hydrochloride of effective dose are processed slow releasing preparation, and said slow releasing preparation is the gastric floating slow-release granular preparation; It is with the effective dose ibuprofen 60%～90%, pseudoephedrine hydrochloride and hydroxypropyl emthylcellulose pulverize separately sieve; Put in the boiling granulating machine fluid bed, mix homogeneously is heated to 60～80 ℃; Hydroxypropyl emthylcellulose is dissolved in is configured to Gonak in the alcoholic solution, with the Gonak spray granulation, be drying to obtain;
The chlorphenamine maleate of surplus ibuprofen and effective dose is processed quick releasing formulation, and said quick releasing formulation is a solid dispersion immediate-release granules preparation; It is with chlorphenamine maleate and polyethylene glycol 6000 mix homogeneously, pulverizes with the micropowder pulverizer, adds Tween 80 solution, and mix homogeneously is put grinding in ball grinder with mixture and prepared solid dispersion; Solid dispersion is added the ibuprofen of cross-linked pvp, lactose and surplus, granulate with alcoholic solution, drying makes;
Again slow releasing preparation and quick releasing formulation are processed various pharmaceutical preparatioies by conventional method.
2. method for preparing of treating the compound medicine of flu is characterized in that:
A. the particulate preparation of gastric floating slow-release:
With the effective dose ibuprofen 60%～90%, 99.5%～99.95% pulverize separately of the pseudoephedrine hydrochloride of effective dose and an amount of hydroxypropyl emthylcellulose crosses 80～200 mesh sieves; Put in the boiling granulating machine fluid bed; Mix homogeneously is heated to 60～80 ℃, and again the hydroxypropyl emthylcellulose of surplus being dissolved in percentage by volume is that to be configured to mass percent in 40%～60% the alcoholic solution be 0.5%～2% Gonak; With this Gonak spray granulation; Stop spraying when better to shaping particles, dry 20～40 minutes, promptly get the gastric floating slow-release granule;
B. the preparation of solid dispersion immediate-release granules:
With the chlorphenamine maleate and the polyethylene glycol 6000 mix homogeneously of effective dose, to pulverize with the micropowder pulverizer, powder particle diameter reaches more than 200 orders, adds the Tween 80 aqueous solution, and mix homogeneously is with the powerful preparation solid dispersion that grinds in the mixture Place grinding machine; With the ibuprofen, cross-linked pvp and the lactose that add surplus in the gained solid dispersion, the use percentage by volume is 60～80% alcoholic solution granulation, and 40 ℃ are dried to substantially anhydrous branch, process immediate-release granules;
C. above-mentioned slow-releasing granules that makes and immediate-release granules are added lubricant respectively, use the bi-layer tablet press tabletting, slow-releasing granules is pressed into inner layer piece, and immediate-release granules is pressed into outer-skin sheet, makes tablet.
3. the method for preparing of compound medicine as claimed in claim 2; It is characterized in that: it comprises 1～3 part of 100 parts of ibuprofen, 10～20 parts of pseudoephedrine hydrochlorides, 1～2 part of chlorphenamine maleate, 5～20 parts of hydroxypropyl emthylcelluloses, 1～2 part of polyethylene glycol 6000,10～40 parts of cross-linked pvps, 10～40 parts of lactose, 0.01～0.09 part of 0.04～0.06g/ml Tween 80 aqueous solution and lubricant said compound medicine, in weight portion.
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| CN103768060B (en) * | 2014-01-26 | 2015-06-17 | 悦康药业集团有限公司 | Compound tablet of ibuprofen, pseudoephedrine hydrochloride and chlorpheniramine maleate |
| CN103787958B (en) * | 2014-03-10 | 2016-01-27 | 悦康药业集团有限公司 | Chlorpheniramine maleate compound and pharmaceutical composition thereof |
| CN106389794A (en) * | 2016-12-06 | 2017-02-15 | 郑州郑先医药科技有限公司 | Medicine for treating common cold and preparation method thereof |
| GB2595301B (en) * | 2020-05-21 | 2025-01-08 | Reckitt Benckiser Health Ltd | Novel Formulation |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1473568A (en) * | 2003-04-14 | 2004-02-11 | 辽宁大生药业有限公司 | Medicinal composition containing Brufen for treating cold |
| CN1785167A (en) * | 2005-10-08 | 2006-06-14 | 王鸣 | Method for preparing composite delayed-release prepn. of non-narcotic analgesic |
| CN1868466A (en) * | 2005-05-26 | 2006-11-29 | 张利 | Buluoweima slow-release tablet and its preparing method |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1473568A (en) * | 2003-04-14 | 2004-02-11 | 辽宁大生药业有限公司 | Medicinal composition containing Brufen for treating cold |
| CN1868466A (en) * | 2005-05-26 | 2006-11-29 | 张利 | Buluoweima slow-release tablet and its preparing method |
| CN1785167A (en) * | 2005-10-08 | 2006-06-14 | 王鸣 | Method for preparing composite delayed-release prepn. of non-narcotic analgesic |
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