CN101422611A - Compound preparation and preparation method thereof - Google Patents
Compound preparation and preparation method thereof Download PDFInfo
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- CN101422611A CN101422611A CNA2008102175700A CN200810217570A CN101422611A CN 101422611 A CN101422611 A CN 101422611A CN A2008102175700 A CNA2008102175700 A CN A2008102175700A CN 200810217570 A CN200810217570 A CN 200810217570A CN 101422611 A CN101422611 A CN 101422611A
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Abstract
The invention discloses a compound preparation and a preparation method thereof, which have technological problems to be solved that compound medicament constituents are used for forming a compound medicament resin composite proportionally, and the containing components have weight proportions as follows: 0.01 to 20.0 percent of compound activity medicament and 2 to 50.0 percent of ion exchange resin; the ion exchange resin is used as a carrier, and the compound activity medicament forms compound activity medicament resin particles with sizes of 850 to 25Mum by being absorbed on the ion exchange resin. The preparation method comprises the following steps: the compound medicament ion exchange resin particles are prepared and mixed with a disintegrating agent, a flavoring agent, a coloring agent, an aromatic agent and an excipient, and pressed into tablets. Compared with the prior art, the ion exchange resin is used as a carrier, and the compound activity medicament forms the compound activity medicament resin particles by being absorbed on the ion exchange resin proportionally, and the proportions of the compound medicament activity constituents are unchanged, and the prepared formulation products is high in stability, simple in process, low in cost and easy in realizing industrialization.
Description
Technical field
The present invention relates to a kind of chemicals preparation and preparation method thereof, the preparation method of particularly a kind of compound medicinal formulation and industrial applications thereof.
Background technology
Along with people's deepening continuously to health idea understanding, the medicine closely bound up with health of people is subjected to more concern, the cry of rational use of drug, safe medication is more and more higher, the modern medication theory of " with minimum medication amount; reach the highest bioavailability; obtain best therapeutic effect, and drop to the risk of adverse effect minimum " progressively is rooted in the hearts of the people, and then also more and more higher to the requirement of medicine and preparation; Be accompanied by the develop rapidly of the deep and preparation process technology of drug delivery system theoretical research, drug delivery system and route of administration aspect have produced a lot of innovative technologies, for example slow releasing preparation, durative action preparation, targeting drug administration preparation, percutaneous drug delivery preparation etc.Compound preparation can be brought into play the synergism of compound medicine component, and therapeutic effect is much better than single preparations of ephedrine, and reduces the medication number of times, brings great convenience to the patient.Compound slow release preparation is the dosage form of progressively rising in recent years in the compound preparation, such dosage form has not only that the folk prescription slow releasing preparation improves utilization ratio of drug, reduces drug side effect, the advantage of stabilised blood concentration, prolong drug treatment time etc., and taking convenience, improve patient's compliance, more can bring into play the synergism of compound medicine component, improve the safety of drug utilization, so therapeutic effect be much better than single preparations of ephedrine, thereby have extraordinary market prospect, progressively become the focus of research and development.
In the compound oral solid ordinary preparation production process, through regular meeting run into batch or batch with criticize between the prescription ratio of compound active component content and stripping release the difficult problem of deviation often appears, because in actual production process, be difficult to accomplish blended very even owing to each active ingredient of compound preparation, and yield is difficult to accomplish 100%, therefore compound active medicine and the inconsistent phenomenon of prescription ratio occur through regular meeting between criticizing and criticizing or with in batch preparation, and then influence the quality and the performance of product; And the compound oral solid sustained-release preparation is except that the problems referred to above, active ingredient slow-release time concordance has increased the development technique difficulty especially, thereby to the more accurate complexity of manufacturing technique requirent, requires harsher to production equipment, especially industrialization technology exploitation, risk and cost are all very high.The compound oral slow releasing preparation of prior art mainly is compound slow-release tablet or capsule, its technology mainly is ball core (label) art for coating, one active ingredient and slow-release material are made capsule-core, and other active ingredient is coated on outside the capsule-core with coating solution or coating once more, and technological requirement is very high.Such as: Chinese patent application number 00137300.5 disclosed stable extended release oral dosage composition (isoephedrine or salt and dechlorloratadine), by containing the core that isoephedrine is an active ingredient, the outer coating contained the active ingredient dechlorloratadine, carries out extended release coatings film coating at last again and forms.Chinese patent application number 200310119378.3 disclosed compound paracetamol and chlorphenamine maleate slow-release micro-pill and preparation methoies, with active ingredient with binding agent etc. make the ball core again sustained release coating form.For rapid-action and taking convenience, be particularly suitable for the compound liquid preparation of old man and children taking, though simple relatively with respect to the compound solid preparation explained hereafter, the bad mouthfeel of medicine has limited the application of a lot of medicines to a great extent such as bitterness, astringent taste, saline taste etc.The compound recipe liquid slow-release preparation, not only have the problem in the compound solid preparation, also has oral mouthfeel, settleability, the requirement of redispersibility, the compound recipe liquid slow-release preparation of prior art adopts the fluidized bed powder coating, as Chinese patent application number 200510102145.3 disclosed oral liquid sustained-release preparations that contain codeine and chlorphenamine and preparation method thereof, slow releasing agent is to finish by the fluidized bed powder coating, control the release time of codeine and chlorphenamine by the thickness of adjusting coating membrane, there be not thoroughly to solve the sustained release performance of compound active medicine under long-term liquid environment in the prescription, with the conforming problem of compound medicine slow release, and manufacture difficulty is big, the cost height is difficult to realize industrialization.
Summary of the invention
The purpose of this invention is to provide a kind of compound preparation and preparation method thereof, the technical problem that solves is to realize compound medicine active component symbiosis formation compound medicine resin complexes in proportion, second technical problem that the present invention will solve is by ion exchange the ion-type high molecular polymer to be wrapped in the surface of drug-resin complex, delays the release of medicine.
The present invention is by the following technical solutions: a kind of compound preparation, and the weight ratio ingredient that described compound preparation comprises is: compound active medicine 0.01～20.0%, ion exchange resin 2～50.0%; Ion exchange resin is carrier, and the compound active medicine is adsorbed on and forms compound active medical resin microgranule on the ion exchange resin, and compound active medical resin particle size is 850～25 μ m.
Compound preparation of the present invention includes disintegrating agent, the flavoring agent greater than 0 to 10% of weight ratio 1～20%, routine dose coloring agent and aromatic, and all the other are excipient.
Compound preparation of the present invention includes the slow-release material of weight ratio 0.02～5%.
Compound preparation of the present invention includes the suspending agent of weight ratio 1～20.0%, 1～10% acidity regulator, antiseptic, correctives and the coloring agent of routine dose, and all the other are filler.
Compound preparation of the present invention includes the slow-release material of weight ratio 0.02～5%.
A kind of compound preparation, the weight ratio ingredient that described compound preparation comprises is: compound active medicine 0.01～1.0%, ion exchange resin 0.1～10.0%; Ion exchange resin is carrier, and the compound active medicine is adsorbed on and forms compound active medical resin microgranule on the ion exchange resin, and compound active medical resin particle size is 250～25 μ m.
Compound preparation of the present invention includes the suspending agent of weight ratio 0.5～30.0%, 0.1～5% acidity regulator, 0.01～5% complexing of metal ion agent, routine dose antiseptic, correctives, coloring agent, and all the other are water.
Compound preparation of the present invention includes the slow-release material of weight ratio 0.001～1%.
A kind of preparation method of compound preparation, may further comprise the steps: one, take by weighing compound active medicine 0.1～20.0% by weight, the adding purified water adds ion exchange resin 2～50.0% after stirring and making its dissolving, with 100～800 rev/mins of stirrings of rotating speed, 1～6 hour time, do not wash or wash 1～4 time, leave standstill, filter supernatant liquid, precipitum is standby, or takes out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, obtains compound medicine ion exchange resin microgranule; Two, with the disintegrating agent of compound medicine ion exchange resin microgranule, weight ratio 1～20%, the flavoring agent greater than 0 to 10%, the coloring agent and the aromatic of routine dose, remaining excipient mixes getting mixed material in 10～40 minutes; Three, mixed material is pressed into tablet, or is filled to capsule formulation, or make granule.
Method of the present invention obtains behind the compound medicine ion exchange resin microgranule slow-release material with weight ratio 0.02%～5.0%, with isopropyl alcohol or dissolve with ethanol to slow-release material/isopropyl alcohol or alcoholic solution concentration is 0.1%～20%, compound medicine ion exchange resin microgranule after adding precipitum or the dried, under 30～80 ℃ of conditions, with 100～800 rev/mins of stirrings, 1～6 hour time, do not wash or wash 1～4 time, sedimentation, filter, precipitum is taken out, place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, the back is crossed 80～200 mesh sieve granulate and is obtained compound sustained-released medicine ion exchanger resin microgranule, again with the disintegrating agent of weight ratio 1～20%, flavoring agent greater than 0 to 10%, the coloring agent of routine dose and aromatic, remaining excipient mixes.
A kind of preparation method of compound preparation, may further comprise the steps: one, take by weighing compound active medicine 0.1～20.0% by weight, the adding purified water adds ion exchange resin 2～50.0% after stirring and making its dissolving, with 100～800 rev/mins of stirrings, 1～6 hour time, do not wash or wash 1～4 time, leave standstill then, filter supernatant liquid, precipitum is standby, or takes out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, obtains compound medicine ion exchange resin microgranule; Two, with the suspending agent of compound medicine ion exchange resin microgranule, weight ratio 1～10.0%, 1～10.0% acidity regulator, the correctives of routine dose, coloring agent and aromatic, and filler mix, and get mixed material; Three, with mixed material by the specification direct packaging or the packing of further granulating, compound dried suspension.
After method of the present invention obtains compound medicine ion exchange resin microgranule, take by weighing slow-release material 0.02%～5.0% by weight, with isopropyl alcohol or dissolve with ethanol to slow-release material/isopropyl alcohol or alcoholic solution concentration is 0.1%～20%, add precipitum or compound medicine ion exchange resin microgranule, under 30 ℃～80 ° degree conditions, stir with 100～800 rev/mins of rotating speeds, 1～6 hour time, do not wash or wash 1～4 time, sedimentation, filter, precipitum is taken out, mistake 80～200 mesh sieve granulate obtain compound sustained-released medicine ion exchanger resin microgranule after placing 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, with compound medicine slow release ion exchange resin microgranule, the suspending agent of weight ratio 1～10.0%, 1～10.0% acidity regulator, the correctives of routine dose, coloring agent and aromatic, and filler mixes.
A kind of preparation method of compound preparation, may further comprise the steps: one, take by weighing compound active medicine 0.01～1.0% by weight, the adding purified water adds ion exchange resin 0.1～10.0%, 100～800 rev/mins of speeds of agitator after stirring and making its dissolving, 1～6 hour time did not wash or washed 1～4 time, leave standstill, filter supernatant liquid, precipitum is standby, or take out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, obtain compound medicine ion exchange resin microgranule; Two, with precipitum or compound medicine ion exchange resin microgranule, the suspending agent of weight ratio 0.5～30.0%, 0.1～5% acidity regulator, 0.01～5% complexing of metal ion agent, antiseptic, correctives and the coloring agent of routine dose and the deionized water of recipe quantity, be stirred to uniform liquid, by the specification fill, get the compound recipe suspension.
Method of the present invention obtains compound medicine ion exchange resin microgranule, take by weighing slow-release material by weight 0.001%～1.0%, with isopropyl alcohol or dissolve with ethanol to slow-release material/isopropyl alcohol or alcoholic solution concentration is 0.1%～20%, compound medicine ion exchange resin microgranule after precipitum or the dried, under 30 ℃～80 ° degree conditions, stirred 1～6 hour with 100～800 rev/mins rotating speeds, do not wash or wash 1～4 time, leave standstill, sedimentation, filter, precipitum is standby, or take out and to place 30～80 ℃ of temperature to carry out crossing 80～200 mesh sieve granulate behind hot air drying or the drying under reduced pressure to obtain compound sustained-released medicine ion exchanger resin microgranule, with microgranule after compound sustained-released medicine ion exchanger resin precipitum or the dried, the suspending agent of weight ratio 0.5～30.0%, 0.1～5% acidity regulator, 0.01～5% complexing of metal ion agent, the antiseptic of routine dose, correctives and coloring agent, and deionized water, be stirred to uniform liquid, by the specification fill, get compound sustained-released suspension.
The present invention compared with prior art, employing ion exchange resin is carrier, compound active medicine co-absorbed in proportion forms compound active medical resin microgranule on ion exchange resin, the ratio of compound medicine active ingredient no longer changes, the various dosage forms of making, product stability can be high, avoided traditional compound preparation with batch or batch between compound active drug ratios deviation and stripping release inconsistent, can also be applied to compound liquid preparation, avoid the adverse drug mouthfeel to improve patient tolerability, especially can be applied to the preparation of compound slow release preparation, the active ingredient ratio that significantly reduces conventional compound slow release preparation appearance is inconsistent, dissolution time is inconsistent, and technology is simple, and cost is low, easy realization of industrialization more can be applied to the bigger compound recipe liquid slow-release preparation of difficulty and risk.
The specific embodiment:
Below in conjunction with embodiment the present invention is described in further detail.Compound preparation of the present invention is carrier with ion exchange resin, and compound active medicine co-absorbed in proportion forms compound active medical resin microgranule on ion exchange resin, and compound active medical resin microgranule and pharmaceutical adjunct are made compound preparation.Compound active medical resin particle size is 850～25 μ m, is preferably between 250～25 μ m, more preferably 150～25 μ m.Compound active medical resin microgranule and other pharmaceutical adjuncts are made various compound recipe dosage forms.Compound recipe dosage form of the present invention is compound recipe general formulation and compound sustained-released dosage form, and the compound recipe general formulation comprises: compound tablet, compound capsule agent, compound granular agent, compound dried suspension, compound recipe suspensoid; Compound sustained-released dosage form comprises compound sustained-released tablet, compound sustained release capsules agent, compound sustained-released granule, compound sustained-released dry suspension and compound sustained-released liquid preparation.
1, compound tablet of the present invention, compound capsule agent, compound granular agent, the weight ratio ingredient that comprises is: active medicine 0.1～20.0%, ion exchange resin 2～50.0%, disintegrating agent 1～20%, flavoring agent 0～10%, routine dose coloring agent and aromatic, all the other are excipient.Active medicine forms microgranule in prescription ratio co-absorbed on ion exchange resin.
2, compound dried suspension of the present invention, the weight ratio ingredient that comprises is: active medicine 0.1～20.0%, ion exchange resin 2～50.0%, suspending agent 1～10.0%, acidity regulator 1～10%, the antiseptic of routine dose, correctives and coloring agent, other are filler.Active medicine forms microgranule in prescription ratio co-absorbed on ion exchange resin.
3, compound recipe suspensoid of the present invention, the weight ratio ingredient that comprises is: active medicine 0.01%～1.0%, ion exchange resin 0.1%～10.0%, suspending agent 0.5%～30.0%, acidity regulator 0.1%～5%, complexing of metal ion agent 0.01%～5%, routine dose antiseptic, correctives, coloring agent, all the other form microgranule for the purified water active medicine in prescription ratio co-absorbed on ion exchange resin, the pastille resin particle is evenly distributed in the liquid medium of suspending agent and purified water, and it is aqueous to be suspendible.
4, compound sustained-released tablet of the present invention, compound sustained release capsules agent, compound sustained-released granule, the weight ratio ingredient that comprises is: active medicine 0.1～20.0%, ion exchange resin 2～50.0%, slow-release material 0.02～5%, disintegrating agent 1～20%, flavoring agent 0～10%, routine dose coloring agent and aromatic, all the other are excipient.Active medicine forms microgranule in prescription ratio co-absorbed on ion exchange resin, be coated with slow-release material.
5, compound sustained-released dry suspension of the present invention, the weight ratio ingredient that comprises is: active medicine 0.～20.0%, ion exchange resin 2～50.0%, slow-release material 0.02～5%, suspending agent 1～10.0%, acidity regulator 1～10%, the antiseptic of routine dose, correctives and coloring agent, other are filler.Active medicine forms microgranule in prescription ratio co-absorbed on ion exchange resin.
6, compound sustained-released liquid preparation of the present invention, the weight ratio that comprises is: active medicine 0.01%～1.0%, ion exchange resin 0.1%～10.0%, suspending agent 0.5%～30.0%, slow-release material 0.001%～1.0%, acidity regulator 0.1%～5%, complexing of metal ion agent 0.01%～5%, routine dose antiseptic, correctives, coloring agent, all the other are purified water.Active medicine forms microgranule in prescription ratio co-absorbed on ion exchange resin, microgranule is coated with slow-release material, contains in the liquid medium that the medicated resin coated particle is evenly distributed on suspending agent and purified water, and it is aqueous to be suspendible.
Active medicine of the present invention is for using compound medicine clinically always, the preferred half-life of slow releasing preparation is short, is necessary the nicotinic acid with the other drug prescription, ibuprofen, ketoprofen, flurbiprofen, aspirin, naproxen sodium, diclofenac sodium, dissolve dilatory azoles sodium, theophylline, dextromethorphan hydrobromide, cetirizine hydrochloride, pseudoephedrine hydrochloride, galantamine, vincamine, pseudoephedrine sulfate, etodolac, indapamide, codeine phosphate, the morphine hydrochloride slow release, the morphine hydrochloride slow release, BUPROPIONE HCl, metformin hydrochloride, BUPROPIONE HCl, spectinomycin hydrochloride, the pseudo-numb sulphur alkali of sulphuric acid, tamsulosin hydrochloride, VENLAFAXINE HCL, tramadol hydrochloride, valaciclovir hydrochlordide, Buflomedil Hydrochloride, verapamil hydrochloride, BUPROPIONE HCl, salbutamol sulfate, diltiazem hydrochloride, pseudoephedrine hydrochloride, ambroxol hydrochloride, benproperine phosphate, pentoxifylline, BUPROPIONE HCl, Buflomedil Hydrochloride, nefopam hydrochloride, ditropan XL, gentamycin sulfate, codeine phosphate, alfuzosin hydrochloride, metroprolol succinate, hydrochloric acid Barney, dihydroergotoxine methanesulfonate, and suitable prescription medicine.
Preferred drug regimen is loratadine-pseudoephedrine sulfate, ibuprofen-pseudoephedrine hydrochloride, isosorbide mononitrate-aspirin, pseudoephedrine hydrochloride-chlorphenamine maleate, pseudoephedrine sulfate-chlorphenamine maleate, codeine phosphate-chlorphenamine maleate, the appropriate sand of codeine phosphate-benzene is quick, hydrocodone-chlorphenamine maleate, nicotinic acid-simvastatin, phenylpropanolamine HC1-chlorphenamine maleate, cetirizine hydrochloride-pseudoephedrine hydrochloride slow release, hydrochloric acid non-sofinadine-pseudoephedrine hydrochloride slow release, metformin hydrochloride-glibenclamide, codeine phosphate-pseudoephedrine hydrochloride-chlorphenamine maleate, codeine phosphate-pseudoephedrine sulfate-chlorphenamine maleate, the similar medicine that acidic group or base are different and its combination.
Ion exchange resin adopts more than one in styrene strong-acid ion exchange resin, styrene weak-acid ion exchange resin, styrene strong basic ion exchange resin, styrene weak-base ion-exchange resin, acrylic acid strong-acid ion exchange resin, acrylic acid weak-acid ion exchange resin, methacrylic acid strong-acid ion exchange resin, the methacrylic acid weak-acid ion exchange resin.The styrene storng-acid cation exchange resin has sulfonic group or phosphate functional group, the styrene weak-acid cation-exchange resin has carboxylic acid group or phenolic acid base functional group, the styrene strong basic ion exchange resin has the season amido functional group, the exchange of styrene weakly-basic anion has primary amine groups-NH2, secondary amine-NHR or tertiary amine groups-NR functional group, acrylic or methacrylic acid weak-acid cation-exchange resin has carboxylic acid group or phenolic acid base functional group, and acrylic or methacrylic acid weak-base anion-exchange resin has amidine functional group.The preferred 50wx2 of styrene storng-acid cation exchange resin, 50wx4,50wx8 (DOW Chemical company limited),
IRP 120, IRP 69 (ROHM AND HAAS Investment Co., Ltd), the preferred DOWEX MAC-3 of styrene weak-acid cation-exchange resin (DOW Chemical company limited),
IRP 64, IRP 88 (ROHM AND HAAS Investment Co., Ltd)), the styrene strong basic ion exchange resin is preferred
IRA 458,
IRA 400 (ROHM AND HAAS Investment Co., Ltd)), DOWEX 22, MARATHON 550A (OH) (DOW Chemical company limited), the styrene weakly-basic anion exchanges preferred AMBERLITETM ITA67 (ROHM AND HAAS Investment Co., Ltd)), DOWEX MONOSPHERE 66 (DOW Chemical company limited) disintegrating agent adopts: in dried starch carboxylic, methyl starch sodium CMS-Na, low substituted hydroxy-propyl methylcellulose L-HPC, crospolyvinylpyrrolidone PVP, Polyethylene Glycol PEG, the gas-producing disintegrant (by sodium bicarbonate and citric acid combination) two kinds reach more than.
Suspending agent adopts: hydroxypropyl emthylcellulose, hydroxypropyl cellulose, methylcellulose, sodium carboxymethyl cellulose, sucrose, propylene glycol, glycerol, sorbitol, maltose alcohol, lactose, Ka Baimu, xanthan gum, tragakanta, polyvidone, polyacrylic acid crosslinked polymer, microcrystalline Cellulose more than one.
Acidity regulator adopts: in sodium phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate, citric acid, the sodium citrate more than one.
The complexing of metal ion agent: citric acid, sodium citrate, ethylenediaminetetraacetic acid, disodiumedetate, in calcium disodium chelate, the diethyl pentetic acid calcium disodium more than one.
Slow-release material adopts the macromolecular material with slow-release function that can be complementary with ion exchange resin, is specially described slow-release material and produces for the polyacrylic resin II, the polyacrylic resin III that meet Chinese Pharmacopoeia (version in 2005) standard, polyacrylic resin IV, poly-first ammonium acrylate ester I, poly-first ammonium acrylate ester II or German Degussa company
E100,
EPO,
L100-55,
L30D-55,
L100,
S100,
RL100,
RL PO,
RL30D,
RS100,
RSPO,
RS30D,
NE30D,
More than one preferably have the high molecular slow-release material of carboxyl functional group or amidine functional group among the FS30D.
The preparation method of compound preparation of the present invention comprises:
1, compound tablet, the compound capsule agent, the preparation method of compound granular agent, may further comprise the steps: one, take by weighing compound active medicine 0.1～20.0% by weight, add and be equipped with in the container of purified water, stirring makes its dissolving back (Japanese EYELA, MAZELA Z type liquid stirrers), add ion exchange resin 2～50.0%, 100～800 rev/mins of speeds of agitator, 1～6 hour time, do not wash or wash 1～4 time, leave standstill then, filter supernatant liquid, precipitum is taken out, place 30～80 ℃ of temperature to carry out hot air drying (Chongqing four reaches experimental apparatus company limited CS101-2E type electric drying oven with forced convection) or drying under reduced pressure (Japanese EYELA, VOS-451SD type vacuum drying oven), 80～200 mesh sieve granulate are crossed in the back, obtain compound medicine ion exchange resin microgranule; Two, with the disintegrating agent of compound medicine ion exchange resin microgranule, weight ratio 1～20%, 1～10% flavoring agent, the coloring agent and the aromatic of routine dose, remaining excipient, put into three-dimensional multinomial mixer (the multinomial movement mixer of SDH-50 type of Jiangyin rarity rubber and plastics machine company limited), mix getting mixed material in 10～40 minutes; Three, mixed material is pressed into tablet (the upright company limited ZP-10A rotary tablet machine of Beijing traditional Chinese medicines dragon) by convas tablet production technology (dry granulation or wet granule compression tablet or direct compression), promptly gets compound tablet by specification cover blister package (DPT130A of Chunguang Packing machinery Co., Ltd., Jinzhou Aluminium-coating Packer); Or press capsule production technology commonly used (granulate and fill or directly filling) and fill suitable capsule formulation (NJP-400B of Zhejiang Fuchang Machinery Co., Ltd. capsule filler), promptly get the compound capsule agent by specification cover blister package (DPT130A of Chunguang Packing machinery Co., Ltd., Jinzhou Aluminium-coating Packer); Or, promptly get the compound granular agent by specification granule racking machine (the Japanese SAMP7-D of Sanko Machinery Co., Ltd. automatic stuffing packager) packing by granule production technology granulation commonly used (SHK-20TS of Beijing Aeronautics Research Inst wet granulator).
2, the preparation method of compound dried suspension, may further comprise the steps: one, take by weighing compound active medicine 0.1～20.0% by weight, add and be equipped with in the container of purified water, after stirring makes its dissolving, add ion exchange resin 2～50.0%, 100～800 rev/mins of speeds of agitator, 1～6 hour time, do not wash or wash 1～4 time, leave standstill then, filter supernatant liquid, precipitum is taken out, place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, the back is crossed 80～200 mesh sieve granulate and is obtained compound medicine ion exchange resin microgranule; Two, with the suspending agent of compound medicine ion exchange resin microgranule, weight ratio 1～10.0%, 1～10.0% acidity regulator, the correctives of routine dose, coloring agent and aromatic, and filler, 100～800 rev/mins of three-dimensional multinomial mixing rotating speeds, 10～40 minutes time (the multinomial movement mixer of SDH-50 type of Jiangyin rarity rubber and plastics machine company limited), get mixed material; Three, with mixed material by dry suspension production technology commonly used, granulate or directly by specification packing (the Japanese SAMP7-D of Sanko Machinery Co., Ltd. automatic stuffing packager), compound dried suspension.
3, the preparation method of compound recipe suspensoid, may further comprise the steps: one, take by weighing compound active medicine 0.01～1.0% by weight, add and be equipped with in the container of purified water, after stirring makes its dissolving, add ion exchange resin 0.1～10.0%, 100～800 rev/mins of speeds of agitator, 1～6 hour time, do not wash or wash 1～4 time, filter supernatant liquid, precipitum is standby or take out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, and the back is crossed 80～200 mesh sieve granulate and obtained compound medicine ion exchange resin microgranule; Two, with the suspending agent of compound medicine ion exchange resin microgranule, weight ratio 0.5～30.0% after precipitum or the dried, 0.1～5% acidity regulator, 0.01～5% complexing of metal ion agent, antiseptic, correctives and the coloring agent of routine dose and the deionized water of recipe quantity, be stirred to uniform liquid (Japanese EYELA, MAZELA Z type liquid stirrers), filling machine gets the compound recipe suspension by specification fill (Jinan fast plant equipment company limited KLG-125 granule filling machine).
4, compound sustained-released tablet, the compound sustained release capsules agent, the preparation method of compound sustained-released granule, may further comprise the steps: one, take by weighing compound active medicine 0.1～20.0% by weight, add and be equipped with in the container of purified water, after stirring makes its dissolving, add ion exchange resin 2～50.0%, 100～800 rev/mins of speeds of agitator, 1～6 hour time, leave standstill then, do not wash or wash 1～4 time, filter supernatant liquid, precipitum is standby or take out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, and the back is crossed 80～200 mesh sieve granulate and obtained compound medicine ion exchange resin microgranule; Two, slow-release material with weight ratio 0.02%～5.0%, with isopropyl alcohol or dissolve with ethanol to concentration is 0.1%～20% (slow-release material/isopropyl alcohol or alcoholic solution), compound medicine ion exchange resin microgranule after adding precipitum or the dried, under 30～80 ℃ of degree conditions, with 100～800 rev/mins of stirrings (MAZELA Z type liquid stirrers Japan EYELA), 1～6 hour time, sedimentation, filter, precipitum is taken out, place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, the back is crossed 80～200 mesh sieve granulate and is obtained compound sustained-released medicine ion exchanger resin microgranule; Three, with the disintegrating agent of compound sustained-released medicine ion exchanger resin microgranule, weight ratio 1～20%, 1～10% flavoring agent, the coloring agent and the aromatic of routine dose, and excipient, three-dimensional multinomial mixing 10～40 minutes (the multinomial movement mixer of SDH-50 type of Jiangyin rarity rubber and plastics machine company limited) gets mixed material; Four, mixed material is pressed into tablet by convas tablet production technology (dry granulation or wet granule compression tablet or direct compression), promptly gets compound sustained-released tablet by specification cover blister package; Or press capsule production technology commonly used (granulate and fill or directly filling) and fill suitable capsule formulation, promptly get the compound sustained release capsules agent by specification cover blister package; Or by granule production technology commonly used, granulate, promptly get compound sustained-released granule by the packing of specification granule racking machine.
5, the preparation method of compound sustained-released dry suspension, may further comprise the steps: one, take by weighing compound active medicine 0.1～20.0% by weight, add and be equipped with in the container of purified water, after stirring makes its dissolving, add ion exchange resin 2～50.0%, 100～800 rev/mins of speeds of agitator, 1～6 hour time, leave standstill then, do not wash or wash 1～4 time, filter supernatant liquid, precipitum is standby, or takes out and to place 30～80 ℃ of temperature to carry out crossing 80～200 mesh sieve granulate behind hot air drying or the drying under reduced pressure to obtain compound medicine ion exchange resin microgranule; Two, take by weighing slow-release material 0.02%～5.0% by weight, with isopropyl alcohol or dissolve with ethanol to concentration is 0.1%～20% (slow-release material/isopropyl alcohol or alcoholic solution), add precipitum or compound medicine ion exchange resin microgranule, under 30 ℃～80 ° degree conditions, stir (Japanese EYELA with 100～800 rev/mins of rotating speeds, MAZELAZ type liquid stirrers), 1～6 hour time, sedimentation, filter, precipitum is taken out, place 30～80 ℃ of temperature to carry out crossing 80～200 mesh sieve granulate behind hot air drying or the drying under reduced pressure and obtain compound sustained-released medicine ion exchanger resin microgranule; Three, with compound medicine slow release ion exchange resin microgranule, the suspending agent of weight ratio 1～10.0%, 1～10.0% acidity regulator, the correctives of routine dose, coloring agent and aromatic, and filler, three-dimensional multinomial mixing 10～40 minutes (the multinomial movement mixer of SDH-50 type of Jiangyin rarity rubber and plastics machine company limited) gets mixed material; Four, with mixed material by dry suspension production technology commonly used, granulate or directly by specification packing (SAMP7-D automatic stuffing packager, Japanese Sanko Machinery Co., Ltd.), compound sustained-released dry suspension.
6, compound sustained-released liquid preparation, may further comprise the steps: one, take by weighing compound active medicine 0.01～1.0% by weight, add and be equipped with in the container of purified water, after stirring makes its dissolving, add ion exchange resin 0.1～10.0%, 100～800 rev/mins of speeds of agitator, 1～6 hour time, do not wash or wash 1～4 time, filter supernatant liquid, precipitum is standby or take out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, and the back is crossed 80～200 mesh sieve granulate and obtained compound medicine ion exchange resin microgranule; Two, take by weighing slow-release material by weight 0.001%～1.0%, with isopropyl alcohol or dissolve with ethanol to concentration is 0.1%～20% (slow-release material/isopropyl alcohol or alcoholic solution), the precipitum or the compound medicine ion exchange resin microgranule that add step 1, under 30 ℃～80 ° degree conditions, stirred 1～6 hour with 100～800 rev/mins rotating speeds, sedimentation, filtration, precipitum is taken out, place 30～80 ℃ of temperature to carry out crossing 80～200 mesh sieve granulate behind hot air drying or the drying under reduced pressure and obtain compound sustained-released medicine ion exchanger resin microgranule; Three, with the precipitum of step 2 or compound sustained-released medicine ion exchanger resin microgranule, the suspending agent of weight ratio 0.5～20.0%, 0.1～5% acidity regulator, 0.01～5% complexing of metal ion agent, antiseptic, correctives and the coloring agent of routine dose, and deionized water, be stirred to uniform liquid, filling machine gets compound sustained-released suspensoid by the specification fill.
The compound recipe dosage form of method preparation of the present invention, test item sees Table 1, and content, release, dissolution, granularity and the suspension ability method of inspection are as follows:
Content and ratio measuring method: press the single taking dose, get 6 units of test sample, drop into the 1000ml volumetric flask respectively, contain KCl solution (the volume ratio methanol/0.7M KCl solution=1:1), stirred 12 hours of methanol, same solution standardize solution, get solution 10ml, filter with 0.45 μ m filter membrane, precision is measured subsequent filtrate 20 μ l, inject chromatograph of liquid, the record chromatogram; Precision takes by weighing preparation single dose active medicine reference substance, and same methanol Klorvess Liquid dissolving standardize solution is got solution 10ml, filters with 0.45 μ m filter membrane, and precision is measured subsequent filtrate 20 μ l, injects chromatograph of liquid, the record chromatogram; In the ratio of external standard method with compound active medicament contg among calculated by peak area the present invention and compound active medicine; Content is not less than sign amount 90%～110%, and the active medicine ratio is not less than 95%～105% of sign amount ratio.
Dissolution method: by " Chinese Pharmacopoeia 2005 editions " appendix XC dissolution method second method, with 37 ℃ of 0.15M KCl solution is release medium, rotating speed is that per minute 75 changes, got solution 5ml respectively at per 15 minutes and 45 minutes, filter and in stripping rotor, replenish immediately equal volume with 0.45 μ m filter membrane, the release medium of uniform temp, precision is measured subsequent filtrate 20 μ l, inject chromatograph of liquid, the record chromatogram, by external standard method with active medicine among calculated by peak area the present invention in the burst size of different time, 15 minutes stripping quantities are not less than 60%, 45 minute of sign amount and are not less than stripping quantity 75%.
Drug release determination method: by " Chinese Pharmacopoeia 2005 editions " appendix XD drug release determination method first method, adopt dissolution method second subtraction unit, be release medium with 37 ℃ of different ions concentration KCl solution respectively, rotating speed is that per minute 75 changes, operation in accordance with the law, at 1 hour, when 4 hours and 10 hours, get solution 5ml respectively, filter with 0.45 μ m filter membrane, and in stripping rotor, replenish equal volume immediately, the release medium of uniform temp, precision is measured subsequent filtrate 20 μ l, injects chromatograph of liquid, the record chromatogram, by external standard method with active medicine among calculated by peak area the present invention in the burst size of different time, 1 hour burst size is that 40%～75%, 10 hours burst sizes that 15%～45%, 4 hours burst sizes of sign amount are the sign amount are not less than knowledge amount 70%.
Particle size detection method: can not and can must not surpass by a sieve (2000 μ m) by the summation of No. five sieves (180 μ m) for 15% of examination amount by " Chinese Pharmacopoeia 2005 editions " appendix IN granule [granularity] item.The settling volume ratio: by " Chinese Pharmacopoeia 2005 editions " appendix IO oral solution oral suspensions Orally taken emulsion item [settling volume ratio] detection method, the settling volume ratio should be not less than 0.90.
1000 bags of embodiment 1 compound recipe phenylpropanolamine granules (specification phenylpropanolamine HC1 25mg, chlorphenamine maleate 1mg/ bag), prescription:
Phenylpropanolamine HC1 25g
Chlorphenamine maleate 1g
Amberlite IRP 120 20g
Polyvinylpyrrolidone 10g
Citric acid 10g
Sodium citrate 8g
Sucrose is to 1000g
Technological parameter sees Table 2, and testing result sees Table 3.
The right romilar sheet of embodiment 2 compound recipe hydrobromic acids, 1000 (the right romilar 20mg of specification hydrobromic acid, chlorphenamine maleate 4mg/ sheet), prescription:
The right romilar 20g of hydrobromic acid
Phenyltoloxamine 4g
Hydroxypropyl emthylcellulose 6g
Carboxymethyl starch sodium 10g
Citric acid 10g
Lactose is to 100g
Technological parameter sees Table 2, and testing result sees Table 3.
Embodiment 3 compound codeine phosphate capsules, 1000 (specification compound codeine phosphate 30mg, phenyltoloxamine 10mg/ grain), prescription:
Codeine phosphate 30g
Phenyltoloxamine 10
DOW 50wx8 100g
Polyvinylpyrrolidone 40g
Magnesium stearate 2g
Differential silica gel 2g
Lactose is to 200g
Technological parameter sees Table 2, and testing result sees Table 3.
1000 bags of embodiment 4 compound recipe phenylpropanolamine sustained-release granular formulations (specification phenylpropanolamine HC1 75mg, chlorphenamine maleate 3mg/ bag), prescription:
Phenylpropanolamine HC1 75g
Chlorphenamine maleate 3g
IRP 120 60g
Poly-first ammonium acrylate ester II 0.6g
Polyvinylpyrrolidone 30g
Citric acid 30g
Sodium citrate 24g
Sucrose is to 3000g
Technological parameter sees Table 2, and testing result sees Table 3.
The right romilar slow-release dispersible tablets of embodiment 5 compound recipe hydrobromic acids, 1000 (the right romilar 60mg of specification hydrobromic acid, chlorphenamine maleate 8mg/ sheet), prescription:
The right romilar 60g of hydrobromic acid
Phenyltoloxamine 6g
Hydroxypropyl emthylcellulose 14g
Poly-first ammonium acrylate ester II 6g
Carboxymethyl starch sodium 60g
Citric acid 30g
Lactose is to 300g
Technological parameter sees Table 2, and testing result sees Table 3.
Embodiment 6 compound codeine phosphate slow releasing capsulees, 1000 (specification compound codeine phosphate 90mg, phenyltoloxamine 30mg/ grain), prescription:
Codeine phosphate 90g
Phenyltoloxamine 30g
DOW 50wx8 300g
Poly-first ammonium acrylate ester II 30g
Polyvinylpyrrolidone 120g
Magnesium stearate 6g
Differential silica gel 6g
Lactose is to 600g
Technological parameter sees Table 2, and testing result sees Table 3.
1000 bags of embodiment 7 compound recipe pseudoephedrine dry suspension (specification pseudoephedrine hydrochloride 30mg, chlorphenamine maleate 1mg/ bag), prescription:
Pseudoephedrine hydrochloride 30g
Chlorphenamine maleate 1g
Microcrystalline Cellulose 100g
Hydroxypropyl emthylcellulose 4g
Sodium carboxymethyl cellulose 3g
Xanthan gum 3g
Citric acid 10g
Sodium citrate 8g
Sucrose is to 1000g
Technological parameter sees Table 4, and testing result sees Table 5.
1000 bags of embodiment 8 compound recipe pseudoephedrine dry suspension (specification pseudoephedrine hydrochloride 20mg, chlorphenamine maleate 1mg/ bag), prescription:
Pseudoephedrine hydrochloride 20g
Chlorphenamine maleate 1g
Amberlite
IRP88 25g
Microcrystalline Cellulose 20g
Hydroxypropyl emthylcellulose 4g
Sodium carboxymethyl cellulose 3g
Xanthan gum 3g
Citric acid 10g
Sodium citrate 6g
Sucrose is to 100g
Technological parameter sees Table 4, and testing result sees Table 5.
1000 bags of embodiment 9 compound recipe pseudoephedrine dry suspension (specification pseudoephedrine hydrochloride 15mg, chlorphenamine maleate 1mg/ bag), prescription:
Pseudoephedrine hydrochloride 15g
Chlorphenamine maleate 1g
DOWEX MAC-3 100g
Microcrystalline Cellulose 40g
Hydroxypropyl emthylcellulose 4g
Sodium carboxymethyl cellulose 3g
Xanthan gum 3g
Citric acid 10g
Sodium citrate 9g
Sucrose is to 200g
Technological parameter sees Table 4, and testing result sees Table 5.
1000 bags of embodiment 10 compound recipe pseudoephedrine slow-release dry suspensions (specification pseudoephedrine hydrochloride 90mg, chlorphenamine maleate 4mg/ bag), prescription:
Pseudoephedrine hydrochloride 90g
Chlorphenamine maleate 4g
Microcrystalline Cellulose 300g
Hydroxypropyl emthylcellulose 12g
Sodium carboxymethyl cellulose 9g
Xanthan gum 9g
Citric acid 300g
Sodium citrate 24g
Sucrose is to 3000g
Technological parameter sees Table 4, and testing result sees Table 5.
1000 bags of embodiment 11 compound recipe pseudoephedrine slow-release dry suspensions (specification pseudoephedrine hydrochloride 60mg, chlorphenamine maleate 3mg/ bag), prescription:
Pseudoephedrine hydrochloride 60g
Chlorphenamine maleate 3g
RL PO 3g
Microcrystalline Cellulose 60g
Hydroxypropyl emthylcellulose 12g
Sodium carboxymethyl cellulose 9g
Xanthan gum 9g
Citric acid 30g
Sodium citrate 18g
Sucrose is to 300g
Technological parameter sees Table 4, and testing result sees Table 5.
1000 bags of embodiment 12 compound recipe pseudoephedrine slow-release dry suspensions (specification pseudoephedrine hydrochloride 45mg, chlorphenamine maleate 3mg/ bag), prescription:
Pseudoephedrine hydrochloride 45g
Chlorphenamine maleate 3g
DOWEX MAC-3 300g
RL PO 30g
Microcrystalline Cellulose 100g
Hydroxypropyl emthylcellulose 12g
Sodium carboxymethyl cellulose 9g
Xanthan gum 9g
Citric acid 30g
Sodium citrate 27g
Sucrose is to 600g
Technological parameter sees Table 4, and testing result sees Table 5.
100 bottles of embodiment 13 compound recipe codeine suspensions (the every 10ml phosphoric acid of specification codeine 10mg, chlorphenamine maleate 1mg), prescription:
Codeine phosphate 1g
Chlorphenamine maleate 0.1g
Sucrose 100g
Xanthan gum 4g
Microcrystalline Cellulose 1g
Disodiumedetate 0.1g
Citric acid 0.6
Sodium citrate 0.4
Ethyl Hydroxybenzoate 2g
Sodium benzoate 2g
Pigment 0.02g
Essence 0.07g
Purified water is to 1000ml
Technological parameter sees Table 6, and testing result sees Table 7.
Embodiment 14,100 bottles of compound recipe codeine suspensions (the every 5ml phosphoric acid of specification codeine 50mg, chlorphenamine maleate 1mg), and prescription:
Codeine phosphate 10g
Chlorphenamine maleate 0.2g
Sucrose 250g
Xanthan gum 5g
Microcrystalline Cellulose 40g
Sodium carboxymethyl cellulose 5g
Disodiumedetate 5g
Citric acid 3g
Sodium citrate 2g
Ethyl Hydroxybenzoate 2g
Sodium benzoate 2g
Pigment 0.02g
Essence 0.07g
Purified water is to 1000ml
Technological parameter sees Table 6, and testing result sees Table 7.
100 bottles of embodiment 15 compound recipe codeine suspensions (the every 10ml phosphoric acid of specification codeine 20mg, chlorphenamine maleate 2mg), prescription:
Codeine phosphate 2g
Chlorphenamine maleate 0.2g
50wx8 10g
Sucrose 200g
Xanthan gum 4g
Microcrystalline Cellulose 20g
Disodiumedetate 1g
Citric acid 6g
Sodium citrate 4g
Ethyl Hydroxybenzoate 2.7g
Sodium benzoate 2.0g
Pigment 0.02g
Essence 0.07g
Purified water is to 1000ml
Technological parameter sees Table 6, and testing result sees Table 7.
100 bottles of embodiment 16 compound recipe codeine slow-release suspensions (the every 10ml phosphoric acid of specification codeine 5mg, chlorphenamine maleate 1mg), prescription:
Codeine phosphate 0.5g
Chlorphenamine maleate 0.1g
RS PO 0.01g
Sucrose 100g
Xanthan gum 4g
Microcrystalline Cellulose 1g
Disodiumedetate 0.1g
Citric acid 0.6
Sodium citrate 0.4g
Ethyl Hydroxybenzoate 2.7g
Sodium benzoate 2g
Pigment 0.02g
Essence 0.07g
Purified water is to 1000ml
Technological parameter sees Table 6, and testing result sees Table 7.
Embodiment 17,100 bottles of compound recipe codeine slow-release suspensions (the every 5ml phosphoric acid of specification codeine 50mg, chlorphenamine maleate 8mg), and prescription:
Codeine phosphate 10g
Chlorphenamine maleate 0.8g
L100 10g
Sucrose 250g
Xanthan gum 5g
Microcrystalline Cellulose 40g
Sodium carboxymethyl cellulose 5g
Disodiumedetate 5g
Citric acid 3g
Sodium citrate 2g
Ethyl Hydroxybenzoate 2g
Sodium benzoate 2g
Pigment 0.02g
Essence 0.07g
Purified water is to 1000ml
Technological parameter sees Table 6, and testing result sees Table 7.
100 bottles of embodiment 18 compound recipe codeine slow-release suspensions (the every 10ml phosphoric acid of specification codeine 20mg, chlorphenamine maleate 4mg), prescription:
Codeine phosphate 2g
Chlorphenamine maleate 0.4g
50wx8 10g
S100 0.5g
Sucrose 200g
Xanthan gum 4g
Microcrystalline Cellulose 20g
Disodiumedetate 1g
Citric acid 6g
Sodium citrate 4g
Ethyl Hydroxybenzoate 2g
Sodium benzoate 2g
Pigment 0.02g
Essence 0.07g
Purified water is to 1000ml
Technological parameter sees Table 6, and testing result sees Table 7.
Table 1 test item
| Dosage form | Content and ratio | Release | Dissolution | Granularity | Suspension ability |
| Compound tablet | + | — | + | — | — |
| The compound capsule agent | + | — | + | — | — |
| The compound granular agent | + | — | + | + | — |
| Compound dried suspension | + | — | + | — | + |
| Compound sustained-released tablet | + | + | — | — | — |
| The compound sustained release capsules agent | + | + | — | — | — |
| Compound sustained-released granule | + | + | — | + | — |
| Compound sustained-released dry suspension | + | + | — | + | |
| Compound sustained-released suspensoid | + | + | — | — | + |
(+be detection, one needn't detection)
Table 2 embodiment 1-6 technological parameter
Table 3 embodiment 1-6 testing result
Table 4 embodiment 7-12 technological parameter
Table 5 embodiment 7-12 testing result
Table 6 embodiment 13-18 technological parameter
Table 7 embodiment 13-18 testing result
Claims (14)
1. compound preparation, it is characterized in that: the weight ratio ingredient that described compound preparation comprises is: compound active medicine 0.01～20.0%, ion exchange resin 2～50.0%; Ion exchange resin is carrier, and the compound active medicine is adsorbed on and forms compound active medical resin microgranule on the ion exchange resin, and compound active medical resin particle size is 850～25 μ m.
2. compound preparation according to claim 1 is characterized in that: described compound preparation includes disintegrating agent, the flavoring agent greater than 0 to 10% of weight ratio 1～20%, routine dose coloring agent and aromatic, and all the other are excipient.
3. compound preparation according to claim 2 is characterized in that: described compound preparation includes the slow-release material of weight ratio 0.02～5%.
4. compound preparation according to claim 1 is characterized in that: described compound preparation includes the suspending agent of weight ratio 1～20.0%, 1～10% acidity regulator, antiseptic, correctives and the coloring agent of routine dose, and all the other are filler.
5. compound preparation according to claim 4 is characterized in that: described compound preparation includes the slow-release material of weight ratio 0.02～5%.
6. compound preparation, it is characterized in that: the weight ratio ingredient that described compound preparation comprises is: compound active medicine 0.01～1.0%, ion exchange resin 0.1～10.0%; Ion exchange resin is carrier, and the compound active medicine is adsorbed on and forms compound active medical resin microgranule on the ion exchange resin, and compound active medical resin particle size is 250～25 μ m.
7. compound preparation according to claim 6, it is characterized in that: described compound preparation includes the suspending agent of weight ratio 0.5～30.0%, 0.1～5% acidity regulator, 0.01～5% complexing of metal ion agent, routine dose antiseptic, correctives, coloring agent, and all the other are water.
8. compound preparation according to claim 7 is characterized in that: described compound preparation includes the slow-release material of weight ratio 0.001～1%.
9. the preparation method of a compound preparation, may further comprise the steps: one, take by weighing compound active medicine 0.1～20.0% by weight, the adding purified water adds ion exchange resin 2～50.0% after stirring and making its dissolving, with 100～800 rev/mins of stirrings of rotating speed, 1～6 hour time, do not wash or wash 1～4 time, leave standstill, filter supernatant liquid, precipitum is standby, or takes out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, obtains compound medicine ion exchange resin microgranule; Two, with the disintegrating agent of compound medicine ion exchange resin microgranule, weight ratio 1～20%, the flavoring agent greater than 0 to 10%, the coloring agent and the aromatic of routine dose, remaining excipient mixes getting mixed material in 10～40 minutes; Three, mixed material is pressed into tablet, or is filled to capsule formulation, or make granule.
10. the preparation method of compound preparation according to claim 9, it is characterized in that: the described slow-release material that obtains behind the compound medicine ion exchange resin microgranule weight ratio 0.02%～5.0%, with isopropyl alcohol or dissolve with ethanol to slow-release material/isopropyl alcohol or alcoholic solution concentration is 0.1%～20%, compound medicine ion exchange resin microgranule after adding precipitum or the dried, under 30～80 ℃ of conditions, with 100～800 rev/mins of stirrings, 1～6 hour time, do not wash or wash 1～4 time, sedimentation, filter, precipitum is taken out, place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, the back is crossed 80～200 mesh sieve granulate and is obtained compound sustained-released medicine ion exchanger resin microgranule, again with the disintegrating agent of weight ratio 1～20%, flavoring agent greater than 0 to 10%, the coloring agent of routine dose and aromatic, remaining excipient mixes.
11. the preparation method of a compound preparation, may further comprise the steps: one, take by weighing compound active medicine 0.1～20.0% by weight, the adding purified water adds ion exchange resin 2～50.0% after stirring and making its dissolving, with 100～800 rev/mins of stirrings, 1～6 hour time, do not wash or wash 1～4 time, leave standstill then, filter supernatant liquid, precipitum is standby, or takes out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, obtains compound medicine ion exchange resin microgranule; Two, with the suspending agent of compound medicine ion exchange resin microgranule, weight ratio 1～10.0%, 1～10.0% acidity regulator, the correctives of routine dose, coloring agent and aromatic, and filler mix, and get mixed material; Three, with mixed material by the specification direct packaging or the packing of further granulating, compound dried suspension.
12. the preparation method of compound preparation according to claim 11, it is characterized in that: described obtain compound medicine ion exchange resin microgranule after, take by weighing slow-release material 0.02%～5.0% by weight, with isopropyl alcohol or dissolve with ethanol to slow-release material/isopropyl alcohol or alcoholic solution concentration is 0.1%～20%, add precipitum or compound medicine ion exchange resin microgranule, under 30 ℃～80 ° degree conditions, stir with 100～800 rev/mins of rotating speeds, 1～6 hour time, do not wash or wash 1～4 time, sedimentation, filter, precipitum is taken out, mistake 80～200 mesh sieve granulate obtain compound sustained-released medicine ion exchanger resin microgranule after placing 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, with compound medicine slow release ion exchange resin microgranule, the suspending agent of weight ratio 1～10.0%, 1～10.0% acidity regulator, the correctives of routine dose, coloring agent and aromatic, and filler mixes.
13. the preparation method of a compound preparation, may further comprise the steps: one, take by weighing compound active medicine 0.01～1.0% by weight, the adding purified water adds ion exchange resin 0.1～10.0%, 100～800 rev/mins of speeds of agitator after stirring and making its dissolving, 1～6 hour time did not wash or washed 1～4 time, leave standstill, filter supernatant liquid, precipitum is standby, or take out and to place 30～80 ℃ of temperature to carry out hot air drying or drying under reduced pressure, obtain compound medicine ion exchange resin microgranule; Two, with precipitum or compound medicine ion exchange resin microgranule, the suspending agent of weight ratio 0.5～30.0%, 0.1～5% acidity regulator, 0.01～5% complexing of metal ion agent, antiseptic, correctives and the coloring agent of routine dose and the deionized water of recipe quantity, be stirred to uniform liquid, by the specification fill, get the compound recipe suspension.
14. the preparation method of compound preparation according to claim 13, it is characterized in that: the described compound medicine ion exchange resin microgranule that obtains, take by weighing slow-release material by weight 0.001%～1.0%, with isopropyl alcohol or dissolve with ethanol to slow-release material/isopropyl alcohol or alcoholic solution concentration is 0.1%～20%, compound medicine ion exchange resin microgranule after precipitum or the dried, under 30 ℃～80 ° degree conditions, stirred 1～6 hour with 100～800 rev/mins rotating speeds, do not wash or wash 1～4 time, leave standstill, sedimentation, filter, precipitum is standby, or take out and to place 30～80 ℃ of temperature to carry out crossing 80～200 mesh sieve granulate behind hot air drying or the drying under reduced pressure to obtain compound sustained-released medicine ion exchanger resin microgranule, with microgranule after compound sustained-released medicine ion exchanger resin precipitum or the dried, the suspending agent of weight ratio 0.5～30.0%, 0.1～5% acidity regulator, 0.01～5% complexing of metal ion agent, the antiseptic of routine dose, correctives and coloring agent, and deionized water, be stirred to uniform liquid, by the specification fill, get compound sustained-released suspension.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012063257A3 (en) * | 2010-11-10 | 2012-07-26 | Rubicon Research Private Limited | Sustained release compositions |
| CN105250240A (en) * | 2015-08-25 | 2016-01-20 | 江苏先科药业有限公司 | Oral sustained-release preparation containing hydrocodone and chlorpheniramine |
| CN110314234A (en) * | 2018-03-22 | 2019-10-11 | 广东东阳光药业有限公司 | Rosuvastain calcium resin complexes and combinations thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012063257A3 (en) * | 2010-11-10 | 2012-07-26 | Rubicon Research Private Limited | Sustained release compositions |
| CN105250240A (en) * | 2015-08-25 | 2016-01-20 | 江苏先科药业有限公司 | Oral sustained-release preparation containing hydrocodone and chlorpheniramine |
| CN110314234A (en) * | 2018-03-22 | 2019-10-11 | 广东东阳光药业有限公司 | Rosuvastain calcium resin complexes and combinations thereof |
| CN110314234B (en) * | 2018-03-22 | 2023-12-08 | 广东东阳光药业股份有限公司 | Rosuvastatin calcium resin complex and composition thereof |
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| CN101422611B (en) | 2012-04-04 |
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