CN101658508A - Novel enteric controlled-release tablet preparation and preparation method thereof - Google Patents
Novel enteric controlled-release tablet preparation and preparation method thereof Download PDFInfo
- Publication number
- CN101658508A CN101658508A CN200810147260A CN200810147260A CN101658508A CN 101658508 A CN101658508 A CN 101658508A CN 200810147260 A CN200810147260 A CN 200810147260A CN 200810147260 A CN200810147260 A CN 200810147260A CN 101658508 A CN101658508 A CN 101658508A
- Authority
- CN
- China
- Prior art keywords
- parts
- coating
- preparation
- enteric
- medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a novel controlled-release preparation based on osmotic pump preparation and a preparation method thereof. The controlled-release preparation comprises a medicine tablet core containing active medicine, a semipermeable film coating coated on the outer layer of the medicine tablet core and provided with small holes, and an enteric coating arranged at the outermost layer, wherein the medicine tablet core comprises 20-70 parts of danshinolic acid B, 50-250 parts of loading agent, 1-120 parts of osmotic pressure accelerant, 1-20 parts of adhesive and 0.1-20 parts of lubricants; the semipermeable film coating comprises 3-15 parts of semipermeable film coating material and 1 part of plasticizer; and the enteric coating comprises 35-65 parts of enteric coating material, 10-35 parts of plasticizer, 5-15 parts of surface active agent and 10-25 parts of antiplastering aid. The preparation has reasonable composition, better controlled-release effect, long effective duration, little gastrointestinal tract side effects, few influences of individual difference, high safety, and excellent patient compliance, and only needs to be taken twice one day. The invention also discloses a danshinolic acid B enteric controlled-release tablet preparation and a preparation method thereof.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, exactly relate to a kind of novel enteric controlled-release tablet preparation, and relate to the preparation method of this controlled-release tablet preparation.
Background technology
1974, Theeuwes proposed the notion and the structure of elementary elementary osmotic pump, made osmotic pump preparation move towards suitability for industrialized production and clinical practice application.The principle of osmotic pump preparation be utilize the permeability of medicine self and some osmotic pressure promoter be used for provide power for release, in use, in moisture sucks sheet from semipermeable membrane, make to form very high osmotic pressure in the sheet, thereby the saturated aqueous solution that makes medicine in the sheet is disengaged by the aperture on sheet surface; Because semipermeable membrane does not have ductility, the volume in the film remains constant, thus if solid drugs not dissolving fully as yet in the sheet, its saturated solution will be released continuously, thereby reach the effect of constant speed release medicine.
Based on its unique principle, with respect to other oral formulations, osmotic pumps has following advantage: medicine discharges with zero level speed, and blood drug level is stably remained in the treatment concentration range, reduced peak valley phenomenon, the toxicity that the medicine blood concentration fluctuation is produced is reduced to minimum; Therefore can reduce medicining times with respect to the obvious prolongation of ordinary preparation medicine constant release time, make things convenient for the patient; Be subjected to external environment factor (as pH value, gastrointestinal motility etc.) influence little with respect to its rate of releasing drug of other sustained-release preparation, so individual variation is little.
But for the multicomponent medicine, particularly the medicine of plant extract form when being prepared as osmotic pump preparation, is difficult to control the release of medicine usually to reach the purpose that zero level discharges.In addition, because water environment promptly begins to discharge medicine in the osmotic pump preparation self-preparing agent contact, therefore will be difficult to discharge under one's belt the medicine of a great deal of with avoiding, and this for mainly in absorption in the intestinal or under one's belt or under the low pH condition for the unsettled medicine, obviously be disadvantageous.
Therefore, need a kind of novel controlled release preparation, to overcome the above-mentioned shortcoming of existing osmotic pumps dosage form based on osmotic pump preparation.
Summary of the invention
The invention provides a kind of novel controlled release preparation based on osmotic pump preparation, thereby overcome that existing osmotic pumps dosage form is not easy to be used for the multicomponent medicine and the shortcoming of unsettled medicine under low pH condition or under one's belt, thereby enlarged the range of application of osmotic pump preparation.
Osmotic pump preparation provided by the present invention, by the label that comprises medicine and be wrapped in outer field semi permeability film coating and the outermost enteric coating that has aperture and form, its Chinese medicine label comprises 20-70 part active medicine, 50-250 part filler, 1-120 part osmotic pressure promoter, 1-20 part binding agent and 0.1-20 part lubricant; The semi permeability film coating comprises 3-15 part semipermeable membrane coating material and 1 part of plasticizer; Enteric coating comprises that 35-65 part is preferably acrylic acid enteric-coating material, 10-35 part plasticizer, 5-15 part surfactant and 10-25 part antiplastering aid.
Wherein, the weight proportion of medicine label and semi permeability film coating sum and enteric coating is 1: 0.05-0.2; Optimum ratio is 1: 0.08-0.15.
Wherein, the film-coated weight proportion of medicine label and semi permeability is 1: 0.02-0.1; Optimum ratio is 1: 0.03-0.05.
In addition, the present invention also provides a kind of salvianolic acid B enteric controlled-release tablet preparation, it comprises: comprise the medicine label of salvianolic acid B and be wrapped in outer field semi permeability film coating and the outermost enteric coating that has aperture, its Chinese medicine label comprises 20-70 part salvianolic acid B, 50-250 part filler, 1-120 part osmotic pressure promoter, 1-20 part binding agent and 0.1-20 part lubricant; The semi permeability film coating comprises 3-15 part semipermeable membrane coating material and 1 part of plasticizer; Enteric coating comprises that 35-65 part is preferably the enteric-coating material of acrylic resin, 10-35 part plasticizer, 5-15 part surfactant and 10-25 part antiplastering aid.
Said preparation is formed rationally, can be reached controlled-release effect preferably, effectively only need take medicine longer duration, every day twice, gastrointestinal side effect influence littler, individual variation is less, safety good, patient dependence good.
Another object of the present invention provides the preparation method of above-mentioned novel controlled release preparation and salvianolic acid B enteric controlled-release tablet preparation.Described method comprises:
(1) preparation medicine label: get medicine, filler, osmotic pressure promoter and the binding agent of described proportioning, mix homogeneously is granulated, and adds the lubricant of described proportioning again, mixing, and tabletting promptly makes the label that contains medicine;
(2) preparation semi permeability film coating liquid: get the semipermeable membrane coating material and the plasticizer of described proportioning, mix homogeneously adds an amount of coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, and coating makes coated tablet, and coated tablet is dry under 30-60 ℃ of condition, obtains exsiccant coated tablet;
(4) punch: go on foot on the exsiccant coated tablet that makes in (3) with laser or additive method and beat the aperture that one or more diameters are 0.2-1.0mm, standby.
(5) preparation enteric coating liquid: get described enteric-coating material with an amount of coating solvent soaking dissolving, add described plasticizer, surfactant and antiplastering aid, stirring, mixing, filtration, it is standby to make coating solution;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating makes coated tablet, and coated tablet is dry under 30-60 ℃ of condition, obtain exsiccant coated tablet, promptly make described controlled release preparation.
Description of drawings
Three batch sample release profiles of Fig. 1 embodiment 1 preparation.
Fig. 2 Radix Salviae Miltiorrhizae Tabellae and the average plasma concentration curve of salvianolic acid B enteric controlled release tablets.
The specific embodiment
At first, controlled release preparation of the present invention not only can be used for well known to a person skilled in the art unsettled preparation under multicomponent, the low pH value, and is equally applicable to single composition and/or main medicine in intestinal absorption.
Osmotic pump preparation provided by the present invention comprises: comprise the label of medicine and be wrapped in outer field semi permeability film coating and the outermost enteric coating that has aperture, its Chinese medicine label comprises 20-70 part active medicine, 50-250 part filler, 1-120 part osmotic pressure promoter, 1-20 part binding agent and 0.1-20 part lubricant; The semi permeability film coating comprises 3-15 part semipermeable membrane coating material and 1 part of plasticizer; Enteric coating comprises that 35-65 part is preferably the enteric-coating material of acrylic resin, 10-35 part plasticizer, 5-15 part surfactant and 10-25 part antiplastering aid.
Wherein, the weight proportion of medicine label and semi permeability film coating sum and enteric coating is 1: 0.05-0.2; Optimum ratio is 1: 0.08-0.15.
Wherein, the film-coated weight proportion of medicine label and semi permeability is 1: 0.02-0.1; Optimum ratio is 1: 0.03-0.05.
Salvianolic acid B (Salvianolic acid B, Sal B) is the water-soluble phenolic acid compounds of Radix Salviae Miltiorrhizae, is the main effective ingredient of red sage formulation.Modern pharmacological research shows to have pharmacological actions such as stronger antioxidant activity and cardiovascular and cerebrovascular vessel protection.For example can be to the research of the pharmacologically active of salvianolic acid B referring to Zhang Yanjun, Zhang Fayan, Fan Yingchang, salvianolic acid B, tanshinone are to the influence [J] of rabbit Atherosclerosis Model inner skin cell function, the Tianjin traditional Chinese medical science, 2005,22 (4): 328～330; Guo Liping, Gao Xiumei, Zhang Meng etc., the pretreated heart microvascular endothelial cell delay protection of salvianolic acid B effect research [J], the Tianjin traditional Chinese medical science, 2002,19 (1): 41～42; Zhao Guifeng, Li Zhuting, Fan Yingchang, salvianolic acid B is to anoxia Ca in the reoxygenation myocardial cell again
2+The influence of concentration change [J], modern combination of Chinese and Western medicine magazine, 2004,13 (1): 19～20; Wang Jiesong, the tube credit is sincere, Ni Zhenyu, etc., the influence [J] that salvianolic acid B and imperatorin stimulate bovine aortic smooth muscle cells to breed to lysophosphatide phthalein choline, Chinese patent medicine, 2004,35 (6): 662～664; Li Lin, Sun Lisha, Xu Jiangping, salvianolic acid B is to the therapeutical effect [J] of dog myocardial infarction. Chinese patent medicine, 2004,36 (3): 215～218.
Salvianolic acid B is unstable in the gastric juice of pH1.0, has good stability in the enteric liquid of pH6.8, shows in body intestinal absorption result of the test, and salvianolic acid B is better in full intestinal absorption, does not have tangible specific absorption position, is fit to make the sustained-release preparation of obeying twice day.However, because salvianolic acid B is a Chinese medicine extract, is multiple mixture of ingredients during use, comparing with single composition has very big difficulty when making controlled releasing penetrant pump, the release result of salvianolic acid B is disturbed in the existence of other compositions easily, makes to be difficult to control drug release when producing.And just because of these reasons, the applicant does not find the report of the controlled releasing penetrant pump of any relevant salvianolic acid B, has not more found the controlled releasing penetrant pump listing of any salvianolic acid B or has been used to clinical.Therefore, in the present invention, adopt salvianolic acid B to verify controlled release preparation of the present invention as the prototype medicine.
Therefore, the salvianolic acid B enteric controlled-release tablet preparation that the present invention also provides comprises: comprise the medicine label of salvianolic acid B and be wrapped in outer field semi permeability film coating and the outermost enteric coating that has aperture, its Chinese medicine label comprises 20-70 part salvianolic acid B, 50-250 part filler, 1-120 part osmotic pressure promoter, 1-20 part binding agent and 0.1-20 part lubricant; The semi permeability film coating comprises 3-15 part semipermeable membrane coating material and 1 part of plasticizer; Enteric coating comprises that 35-65 part is preferably the enteric-coating material of acrylic resin, 10-35 part plasticizer, 5-15 part surfactant and 10-25 part antiplastering aid.
Wherein, the weight proportion of medicine label and semi permeability film coating sum and enteric coating is 1: 0.05-0.2; Optimum ratio is 1: 0.08-0.15.
Wherein, the film-coated weight proportion of medicine label and semi permeability is 1: 0.02-0.1; Optimum ratio is 1: 0.03-0.05.
Wherein, osmotic pressure promoter in the medicine label is meant the known osmotic pressure promoter of field of pharmaceutical preparations those of ordinary skill, any one or more than one the mixture of preferred potassium chloride, sodium chloride, magnesium chloride, potassium sulfate, sodium sulfate, magnesium sulfate etc., more preferably any one or more than one the mixture in potassium chloride, sodium chloride, the magnesium chloride; Filler is meant the known filler of field of pharmaceutical preparations those of ordinary skill, any one or more than one the mixture of preferably microcrystalline cellulose, dextrin, starch and derivant thereof, mannitol, sorbitol, lactose, sucrose etc., more preferably microcrystalline Cellulose, lactose or their mixture; Binding agent is meant the known binding agent of field of pharmaceutical preparations those of ordinary skill, any one or more than one the mixture of the mixed solution of preferred polyvidone, methylcellulose, sodium carboxymethyl cellulose, carboxylic propyl methocel, water, water or alcohol etc.; Lubricant is meant the known lubricant of field of pharmaceutical preparations those of ordinary skill, preferred magnesium stearate.
The medicine label preferably includes following components in weight percentage: 20-70 part is preferably active medicine, 50-250 part microcrystalline Cellulose, 1-50 part lactose, 1-120 part sodium chloride, 1-20 part 30 POVIDONE K 30 BP/USP 30 and 0.1-20 part magnesium stearate of salvianolic acid B; More preferably proportioning is: 20-50 part is preferably active medicine, 80-120 part microcrystalline Cellulose, 20-40 part lactose, 20-100 part sodium chloride, 1-15 part 30 POVIDONE K 30 BP/USP 30 and 1-10 part magnesium stearate of salvianolic acid B; Further preferred proportioning is: 20-30 part is preferably active medicine, 95-105 part microcrystalline Cellulose, 28-32 part lactose, 58-62 part sodium chloride, 5-7 part 30 POVIDONE K 30 BP/USP 30 and 0.5-2 part magnesium stearate of salvianolic acid B; Preferred proportioning is: 22.5 parts are preferably the active medicine of salvianolic acid B, 101 parts of microcrystalline Cellulose, 30 parts of lactose, 60 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 1 part of magnesium stearate.
Semipermeable membrane coating material in the semipermeable membrane coating is meant the known semipermeable membrane coating material of field of pharmaceutical preparations those of ordinary skill, any one or more than one the mixture of preferred cellulose acetate, ethyl cellulose, cellulose propionate, Merlon, polyethylene, polyvinyl alcohol, vinylacetate etc.; Plasticizer is meant the known plasticizer of field of pharmaceutical preparations those of ordinary skill, any one or more than one the mixture of preferred phthalate, glyceride, succinate, benzoate, phosphate ester, adipate ester, tartrate, polyethylene glycols etc., more preferably any one of polyethylene glycol 1500 or Macrogol 4000 etc. or more than one mixture.
The semi permeability film coating preferably includes following components in weight percentage: 3-15 part cellulose acetate and 1 part of polyethylene glycol 1500; Preferred proportioning is: 3-12 part cellulose acetate and 1 part of polyethylene glycol 1500; Further optimum ratio is: 3-5 part cellulose acetate and 1 part of polyethylene glycol 1500; Preferred proportioning is: 4 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Acrylic resin is meant any one or more than one the mixture in acrylic resin I, II, III number in the enteric-coating material in the enteric coating; Plasticizer is meant the known plasticizer of field of pharmaceutical preparations those of ordinary skill, any one or more than one mixture in preferred liquid paraffin, triethyl citrate, o-benzoic acid diethylester, acetic acid monoglyceride, Oleum Ricini, certain herbaceous plants with big flowers two dibutyl phthalates, the oleic acid, more preferably any one or more than one the mixture of liquid paraffin, o-benzoic acid diethylester, Semen Ricini wet goods; Surfactant is meant the known surfactant of field of pharmaceutical preparations those of ordinary skill, any one or more than one the mixture of preferred Tweens, spans, monovalence ammonium amine soap apoplexy due to endogenous wind, more preferably tween 80; Antiplastering aid is meant the known surfactant of field of pharmaceutical preparations those of ordinary skill, any one or more than one the mixture in preferably talc powder, the Kaolin, preferably talc powder.
Enteric coating preferably includes following components in weight percentage: 35-65 part acrylic resin I number, 5-15 part liquid paraffin, 1-10 part o-benzoic acid diethylester, 5-15 part Oleum Ricini, 5-15 part tween 80 and 10-25 part Pulvis Talci; More preferably proportioning is: 40-55 part acrylic resin I number, 8-13 part liquid paraffin, 2-6 part o-benzoic acid diethylester, 8-13 part Oleum Ricini, 8-13 part tween 80 and 14-18 part Pulvis Talci; Further preferred proportioning is: 42-48 part acrylic resin I number, 11-13 part liquid paraffin, 3-5 part o-benzoic acid diethylester, 11-13 part Oleum Ricini, 11-13 part tween 80 and 13-17 part Pulvis Talci; Preferred proportioning is: 45 parts of acrylic resin I number, 12 parts liquid paraffin, 4 parts of o-benzoic acid diethylesters, 12 parts of Oleum Ricini, 12 parts of tween 80s and 15 parts of Pulvis Talci.
Filler mannitol in the medicine label of being mentioned among the present invention, sorbitol, lactose, sucrose etc. mainly are as filler, but also have the effect of osmotic pressure promoter simultaneously concurrently; Polyethylene glycol 1500 mainly is as plasticizer in the semi permeability film coating, but also has the effect of porogen simultaneously concurrently, and it can improve the permeability of coating membrane, promotes the release of drug solution.
Produce above each embodiment salvianolic acid B enteric controlled-release tablet preparation in a small amount as a trial, products obtained therefrom all meets the provisions of the relevant regulations issued by the State through researchs such as release investigation, assay, related substance inspection and solvent residual amount tests.
On the semi permeability film coating of above-mentioned salvianolic acid B controlled release preparation, can one or more small delivery aperture, preferred one of little hole number be arranged with laser or additive method preparation; Its diameter is 0.2-1.0mm, preferred 0.4-0.8mm.
Danshinolic acid B enteric controlled-release tablet can prepare by the method that may further comprise the steps:
(1) preparation medicine label: get salvianolic acid B, filler, osmotic pressure promoter and the binding agent of described proportioning, mix homogeneously is granulated, and adds the lubricant of described proportioning again, mixing, and tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the semipermeable membrane coating material and the plasticizer of described proportioning, mix homogeneously adds an amount of coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, and coating makes coated tablet, and coated tablet is dry under 30-60 ℃ of condition, obtains exsiccant coated tablet;
(4) punch: go on foot on the exsiccant coated tablet that makes in (3) with laser or additive method and beat the aperture that one or more diameters are 0.2-1.0mm, standby.
(5) preparation enteric coating liquid: get described enteric-coating material with an amount of coating solvent soaking dissolving, add described plasticizer, surfactant and antiplastering aid, stirring, mixing, filtration, it is standby to make coating solution;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating makes coated tablet, and coated tablet is dry under 30-60 ℃ of condition, obtain exsiccant coated tablet, promptly make the salvianolic acid B enteric controlled release tablets.
Wherein, the coating solvent described in (2) step can be that volume ratio is 4-20: 1 acetone-water solution or acetone-alcoholic solution; (4) aperture described in the step is one, and its diameter is 0.4-0.8mm; (5) the coating solvent described in the step can be 95% alcoholic solution.
Compared with prior art, the invention has the beneficial effects as follows: first the enteric coating technology is used for osmotic pump preparation, thereby has produced novel controlled release preparation of the present invention based on osmotic pump preparation.By following example in an embodiment as can be known, unexpectedly has the enteric of can be used for multicomponent medicine according to the inventive method prepared preparation, and medicine release in vivo meets the zero level dispose procedure substantially, promptly with constant speed or near constant release, blood drug level can maintain in the valid density scope for a long time more consistently, thereby effectively longer duration can reduce administration number of times, taking convenience; Blood drug level is steady, and it is less to fluctuate, and can avoid occurring peak valley phenomenon, and gastrointestinal side effect is littler, and safety is good; Because of taking convenience, side effect are little, can guarantee curative effect of medication again, also can improve patient's compliance; And can overcome the shortcoming of ordinary preparation, avoid the Degradation of gastric juice to medicine.
The present invention makes salvianolic acid B the single chamber enteric controlled-release tablet preparation first, and through external dissolution test, 2 hours clothing films are insoluble in simulated gastric fluid, and in simulated intestinal fluid, dissolving in 3 minutes can effectively be kept salvianolic acid B and discharge more than 8 hours.Its drug release rate is not subjected to the influence of gastrointestinal tract pH value, thereby the influence of individual variation is less.And medicine release in vivo meets the zero level dispose procedure substantially, and promptly with constant speed or near constant release, only need take medicine twice every day, taking convenience; Blood drug level is steady, and it is less to fluctuate, and can avoid occurring peak valley phenomenon, and gastrointestinal side effect is littler, and safety is good.Because of taking convenience, side effect are little, can guarantee curative effect of medication again, also can improve patient's compliance.And can overcome the shortcoming of ordinary preparation, avoid the Degradation of gastric juice to salvianolic acid B.
The present invention is described in further detail below in conjunction with the specific embodiment.
Embodiment
Embodiment 1
The film-coated weight proportion of medicine label and semi permeability is 1: 0.035; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 101 parts of microcrystalline Cellulose, 30 parts of lactose, 60 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 1 part of magnesium stearate.
Semi permeability is film-coated to consist of: 4 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Consisting of of enteric coating: 45 parts of acrylic resin I number, 12 parts liquid paraffin, 4 parts of o-benzoic acid diethylesters, 12 parts of Oleum Ricini, 12 parts of tween 80s and 15 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, microcrystalline Cellulose, lactose and the sodium chloride of getting described proportioning, mix homogeneously, 95% alcoholic solution that adds 30 POVIDONE K 30 BP/USP 30 is made soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose acetate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, acetone-95% alcoholic solution that adds volume ratio and be 19: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3.5% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.6mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 12% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.035; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 101 parts of microcrystalline Cellulose, 30 parts of lactose, 60 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 1 part of magnesium stearate; The semi permeability film coating is made up of 4 parts of cellulose acetate and 1 part of polyethylene glycol 1500; Enteric coating is by 45 parts of acrylic resin I numbers, 12 parts liquid paraffin, 4 parts of o-benzoic acid diethylesters, 12 parts of Oleum Ricini, 12 parts of tween 80s and 15 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
The film-coated weight proportion of medicine label and semi permeability is 1: 0.05; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.15 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 105 parts of microcrystalline Cellulose, 40 parts of lactose, 50 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.1 part of magnesium stearate.
Semi permeability is film-coated to consist of: 3 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Consisting of of enteric coating: 55 parts of acrylic resin I number, 10 parts liquid paraffin, 5 parts of o-benzoic acid diethylesters, 10 parts of Oleum Ricini, 10 parts of tween 80s and 10 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, microcrystalline Cellulose, lactose and the sodium chloride of getting described proportioning, mix homogeneously, 85% alcoholic solution that adds 30 POVIDONE K 30 BP/USP 30 is made soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose acetate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, acetone-95% alcoholic solution that adds volume ratio and be 20: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 5% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 60 ℃ of conditions dry 12 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.8mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 15% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.05; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.15, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 105 parts of microcrystalline Cellulose, 40 parts of lactose, 50 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.1 part of magnesium stearate; The semi permeability film coating is made up of 3 parts of cellulose acetate and 1 part of polyethylene glycol 1500; Enteric coating is by 55 parts of acrylic resin I numbers, 10 parts liquid paraffin, 5 parts of o-benzoic acid diethylesters, 10 parts of Oleum Ricini, 10 parts of tween 80s and 10 parts of Pulvis Talci.
Embodiment 3
The film-coated weight proportion of medicine label and semi permeability is 1: 0.02; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.05 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 88 parts of microcrystalline Cellulose, 25 parts of lactose, 80 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/ USPs 30 and 10 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 12 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Consisting of of enteric coating: 50 parts of acrylic resin I number, 9 parts liquid paraffin, 6 parts of o-benzoic acid diethylesters, 15 parts of Oleum Ricini, 8 parts of tween 80s and 12 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, microcrystalline Cellulose, lactose and the sodium chloride of getting described proportioning, mix homogeneously, 95% alcoholic solution that adds 30 POVIDONE K 30 BP/USP 30 is made soft material in right amount, cross 20 mesh sieves and granulate, dry under 60 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose acetate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-water that adds volume ratio and be 4: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 2% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 50 ℃ of conditions dry 18 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 1.0mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 5% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.02; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.05, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 88 parts of microcrystalline Cellulose, 25 parts of lactose, 80 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/ USPs 30 and 10 parts of magnesium stearate; The semi permeability film coating is made up of 12 parts of cellulose acetate and 1 part of polyethylene glycol 1500; Enteric coating is by 50 parts of acrylic resin I numbers, 9 parts liquid paraffin, 6 parts of o-benzoic acid diethylesters, 15 parts of Oleum Ricini, 8 parts of tween 80s and 12 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
The film-coated weight proportion of medicine label and semi permeability is 1: 0.04; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 70 parts of microcrystalline Cellulose, 20 parts of lactose, 90 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/ USPs 30 and 20 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 3 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Consisting of of enteric coating: 35 parts of acrylic resin I number, 10 parts liquid paraffin, 10 parts of o-benzoic acid diethylesters, 10 parts of Oleum Ricini, 15 parts of tween 80s and 20 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, microcrystalline Cellulose, lactose and the sodium chloride of getting described proportioning, mix homogeneously, 95% alcoholic solution that adds 30 POVIDONE K 30 BP/USP 30 is made soft material in right amount, cross 20 mesh sieves and granulate, dry under 55 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose acetate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, acetone-95% alcoholic solution that adds volume ratio and be 10: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 4% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 30 ℃ of conditions dry 36 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.4mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 12% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.04; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 70 parts of microcrystalline Cellulose, 20 parts of lactose, 90 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/ USPs 30 and 20 parts of magnesium stearate; The semi permeability film coating is made up of 3 parts of cellulose acetate and 1 part of polyethylene glycol 1500; Enteric coating is by 35 parts of acrylic resin I numbers, 10 parts liquid paraffin, 10 parts of o-benzoic acid diethylesters, 10 parts of Oleum Ricini, 15 parts of tween 80s and 20 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
The film-coated weight proportion of medicine label and semi permeability is 1: 0.03; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.08 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 130 parts of microcrystalline Cellulose, 40 parts of lactose, 30 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 7 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 15 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Consisting of of enteric coating: 65 parts of acrylic resin I number, 10 parts liquid paraffin, 5 parts of o-benzoic acid diethylesters, 15 parts of Oleum Ricini, 5 parts of tween 80s and 10 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, microcrystalline Cellulose, lactose and the sodium chloride of getting described proportioning, mix homogeneously, 95% alcoholic solution that adds 30 POVIDONE K 30 BP/USP 30 is made soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose acetate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-water that adds volume ratio and be 15: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 45 ℃ of conditions dry 20 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.2mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 8% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.03; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.08, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 130 parts of microcrystalline Cellulose, 40 parts of lactose, 30 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 7 parts of magnesium stearate; The semi permeability film coating is made up of 15 parts of cellulose acetate and 1 part of polyethylene glycol 1500; Enteric coating is by 465 parts of acrylic resin I numbers, 10 parts liquid paraffin, 5 parts of o-benzoic acid diethylesters, 15 parts of Oleum Ricini, 5 parts of tween 80s and 10 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
The film-coated weight proportion of medicine label and semi permeability is 1: 0.035; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 110 parts of microcrystalline Cellulose, 35 parts of lactose, 50 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/ USPs 30 and 2 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 8 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Consisting of of enteric coating: 42 parts of acrylic resin I number, 14 parts liquid paraffin, 6 parts of o-benzoic acid diethylesters, 16 parts of Oleum Ricini, 10 parts of tween 80s and 12 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, microcrystalline Cellulose, lactose and the sodium chloride of getting described proportioning, mix homogeneously, 95% alcoholic solution that adds 30 POVIDONE K 30 BP/USP 30 is made soft material in right amount, cross 20 mesh sieves and granulate, dry under 45 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose acetate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-water that adds volume ratio and be 20: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3.5% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 35 ℃ of conditions dry 30 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.6mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 12% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.035; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 110 parts of microcrystalline Cellulose, 35 parts of lactose, 50 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/ USPs 30 and 2 parts of magnesium stearate; The semi permeability film coating is made up of 8 parts of cellulose acetate and 1 part of polyethylene glycol 1500; Enteric coating is by 42 parts of acrylic resin I numbers, 14 parts liquid paraffin, 6 parts of o-benzoic acid diethylesters, 16 parts of Oleum Ricini, 10 parts of tween 80s and 12 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
Embodiment 7
The film-coated weight proportion of medicine label and semi permeability is 1: 0.025; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.06 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 40 parts of lactose of 110 parts of microcrystalline Cellulose, 40 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.5 part of magnesium stearate.
Semi permeability is film-coated to consist of: 10 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Consisting of of enteric coating: 38 parts of acrylic resin I number, 12 parts liquid paraffin, 10 parts of o-benzoic acid diethylesters, 5 parts of Oleum Ricini, 15 parts of tween 80s and 20 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, microcrystalline Cellulose, lactose and the sodium chloride of getting described proportioning, mix homogeneously, 95% alcoholic solution that adds 30 POVIDONE K 30 BP/USP 30 is made soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose acetate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, acetone-95% alcoholic solution that adds volume ratio and be 10: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 2.5% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.5mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 6% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.025; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.06, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 40 parts of lactose of 110 parts of microcrystalline Cellulose, 40 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.5 part of magnesium stearate; The semi permeability film coating is made up of 10 parts of cellulose acetate and 1 part of polyethylene glycol 1500; Enteric coating is by 38 parts of acrylic resin I numbers, 12 parts liquid paraffin, 10 parts of o-benzoic acid diethylesters, 5 parts of Oleum Ricini, 15 parts of tween 80s and 20 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
The film-coated weight proportion of medicine label and semi permeability is 1: 0.035; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 105 parts of microcrystalline Cellulose, 30 parts of lactose, 55 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/ USPs 30 and 2 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 9 parts of cellulose acetate and 1 part of polyethylene glycol 1500.
Consisting of of enteric coating: 50 parts of acrylic resin I number, 18 parts liquid paraffin, 5 parts of o-benzoic acid diethylesters, 7 parts of Oleum Ricini, 8 parts of tween 80s and 12 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, microcrystalline Cellulose, lactose and the sodium chloride of getting described proportioning, mix homogeneously, 95% alcoholic solution that adds 30 POVIDONE K 30 BP/USP 30 is made soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose acetate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, acetone-95% alcoholic solution that adds volume ratio and be 15: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3.5% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.7mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 12% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.035; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 105 parts of microcrystalline Cellulose, 30 parts of lactose, 55 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/ USPs 30 and 2 parts of magnesium stearate; The semi permeability film coating is made up of 9 parts of cellulose acetate and 1 part of polyethylene glycol 1500; Enteric coating is by 50 parts of acrylic resin I numbers, 18 parts liquid paraffin, 5 parts of o-benzoic acid diethylesters, 7 parts of Oleum Ricini, 8 parts of tween 80s and 12 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
Embodiment 9
The film-coated weight proportion of medicine label and semi permeability is 1: 0.035; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 200 parts of dextrin, 30 parts of sodium chloride, 15 parts of methylcellulose and 12 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 12 parts of ethyl celluloses and 1 part of Macrogol 4000.
Consisting of of enteric coating: 40 parts of acrylic resin I number, 15 parts liquid paraffin, 5 parts of o-benzoic acid diethylesters, 10 parts of Oleum Ricini, 15 parts of tween 80s and 15 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, dextrin, methylcellulose and the sodium chloride of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the ethyl cellulose and the Macrogol 4000 of described proportioning, mix homogeneously, acetone-95% alcoholic solution that adds volume ratio and be 19: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3.5% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.4mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 12% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.035; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.12, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 200 parts of dextrin, 30 parts of sodium chloride, 15 parts of methylcellulose and 12 parts of magnesium stearate; The semi permeability film coating is made up of 12 parts of ethyl celluloses and 1 part of Macrogol 4000; Enteric coating is by 440 parts of acrylic resin I numbers, 15 parts liquid paraffin, 5 parts of o-benzoic acid diethylesters, 10 parts of Oleum Ricini, 15 parts of tween 80s and 15 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
The film-coated weight proportion of medicine label and semi permeability is 1: 0.03; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.1 a salvianolic acid B enteric controlled-release tablet preparation, wherein:
Consisting of of medicine label: 22.5 parts of salvianolic acid Bs, 120 parts of corn starchs, 80 parts of magnesium chlorides, 15 parts of sodium carboxymethyl cellulose and 15 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 9 parts of cellulose propionates and 1 part of tartrate.
Consisting of of enteric coating: 55 parts of acrylic resin I number, 10 parts liquid paraffin, 3 parts of o-benzoic acid diethylesters, 10 parts of Oleum Ricini, 10 parts of tween 80s and 12 parts of Pulvis Talci.
The preparation method of danshinolic acid B enteric controlled-release tablet may further comprise the steps:
(1) preparation medicine label: salvianolic acid B, corn starch, sodium carboxymethyl cellulose and the magnesium chloride of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains salvianolic acid B;
(2) preparation semi permeability film coating liquid: get the cellulose propionate and the tartrate of described proportioning, mix homogeneously, acetone-95% alcoholic solution that adds volume ratio and be 19: 1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3% of medicine label, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.8mm, standby.
(5) preparation enteric coating liquid: get described acrylic resin I number, dissolve as the coating solvent soaking in right amount with 95% ethanol, add described liquid paraffin, o-benzoic acid diethylester, Oleum Ricini, tween 80 and part Pulvis Talci, stirring, mixing, filtration, it is standby to make enteric coating liquid;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, coating to coating weightening finish part is about 10% of medicine label, make coated tablet, with coated tablet under 40 ℃ of conditions dry 24 hours, obtain exsiccant coated tablet, promptly making the film-coated weight proportion of medicine label and semi permeability is 1: 0.03; The weight proportion of medicine label and semi permeability film coating and enteric coating is 1: 0.1, and the medicine label is made up of 22.5 parts of salvianolic acid Bs, 120 parts of corn starchs, 80 parts of magnesium chlorides, 15 parts of sodium carboxymethyl cellulose and 15 parts of magnesium stearate; The semi permeability film coating is made up of 9 parts of cellulose propionates and 1 part of tartrate; Enteric coating is by 55 parts of acrylic resin I numbers, 10 parts liquid paraffin, 3 parts of o-benzoic acid diethylesters, 10 parts of Oleum Ricini, 10 parts of tween 80s and 12 parts of salvianolic acid B enteric controlled-release tablet preparations that Pulvis Talci is formed.
Embodiment 11 drug release tests
For the release conditions of medicine of the present invention is described, the inventor has also carried out the release inspection, and its method is as follows:
Get three batches in the embodiment of the invention 1 prepared example pharmaceuticals preparation, according to 2005 editions two appendix XIXD slow release of Chinese Pharmacopoeia, in controlled release and the slowbreak preparation guideline about the regulation of drug release determination method and dissolution method, with simulated gastric fluid 1000ml is that to use simulated intestinal fluid 1000ml instead after release medium discharges 2 hours be release medium, basket method 100rpm, measure release down for 37 ℃ ± 0.5 ℃, respectively at 1,2,3,4,5,6,8,10,12, sampling 4ml and in time additional dissolution medium 4ml cross 0.45 μ m microporous filter membrane with sample during 14h, get subsequent filtrate, carry out HPLC (2005 editions two appendix of Chinese Pharmacopoeia, you replenish particular content) and measure, calculate the drug accumulation release of above-mentioned each time point.The results are shown in Table 1, three batch sample release profiles and see Figure of description 1:
Three batches of release check results of table 1 sample
| Time (h) | ??2 | ??3 | ??4 | ??5 | ??6 | ??8 | ??10 | ??14 |
| ??1 | ??0 | ??12.1 | ??27.3 | ??40.9 | ??53.8 | ??75.4 | ??91.7 | ??92.4 |
| ??2 | ??0 | ??11.7 | ??26.2 | ??38.7 | ??51.2 | ??73.8 | ??89.4 | ??94.3 |
| ??3 | ??0 | ??12.8 | ??28.7 | ??40.7 | ??53.5 | ??77.3 | ??92.1 | ??93.6 |
| ??RSD(％) | ??0 | ??4.56 | ??4.57 | ??3.03 | ??2.69 | ??2.32 | ??1.60 | ??1.03 |
Conclusion: medicine of the present invention in simulated gastric fluid in 2 hours medicine do not discharge, discharge at the simulated intestinal fluid Chinese medicine, all up to specification in the burst size limit of the 3rd hour, 4 hours, 5 hours, 6 hours and 10 hours.Medicine of the present invention is 5～12% of labelled amount 3-10 hour average rate of release, and is up to specification.Its release meets the zero level dispose procedure substantially, and blood drug level can be maintained in the valid density scope for a long time more consistently, effectively longer duration.
In order to separate the medicine rule and the characteristics of dynamic change in animal body, provide reference to clinical rational drug use, the inventor has also carried out clinical preceding animal pharmacokinetics research to medicine salvianolic acid B enteric controlled release tablets of the present invention (sample of embodiment 1 preparation), and method and result are as follows:
This test is a subjects with beasle dog, is the time dependent rule of blood drug level of the reference preparation medicine of the present invention of having studied same dose and calculates its pharmacokinetic parameter with commercially available Radix Salviae Miltiorrhizae Tabellae.
Before the experiment, select the beasle dog of 6 body weight in 6～8kg scope, be divided into two groups at random, settle one to be detained pin at its forelimb snapshot of oneself vein place, by experienced poultry raiser salvianolic acid B enteric controlled release tablets prepared among the embodiment 1 and commercially available Radix Salviae Miltiorrhizae Tabellae are inserted the oral cavity epiglottis portion of beasle dog then respectively with intact tablet, make beasle dog swallow automatically and inject the 20ml clear water and send down, the reference preparation group is the 0th after the administration, 0.5,1,1.5,2,3,4,5,6,8,12,16,20,24, totally 15 time points of 30h gets forelimb venous blood 4ml, be subjected to the test preparation group the 0th, 1,2,2.5,3,4,6,8,10,12,14,16,20,24, totally 15 time points of 30h gets forelimb venous blood 4ml, and immigration scribbles in the test tube of heparin immediately, centrifugal 10 minutes of 4000rpm, separated plasma is put-20 ℃ of refrigerators then and is preserved stand-by.Intersect after the week at interval and take medicine, take a blood sample with quadrat method.The plasma drug level measurement result sees Table 2 and table 3, and average plasma concentration curve is seen Figure of description 2.
Table 2 salvianolic acid B enteric controlled release tablets blood drug level (μ gml
-1)
Table 3 Radix Salviae Miltiorrhizae Tabellae blood drug level (μ gml
-1)
The result shows: its Ke of salvianolic acid B enteric controlled release tablets single dose administration is 0.06 ± 0.002h
-1, t
1/2Be 11.48 ± 0.33h, AUC is 820.34 ± 17.02 (μ g/ml) h, and Cmax is 53.82 ± 1.07 μ g/ml, and Tmax is 8.67 ± 1.03h; Its Ke of Radix Salviae Miltiorrhizae Tabellae single dose administration is 0.09 ± 0.004h
-1, t
1/2Be 8.10 ± 0.39h, AUC is 435.85 ± 9.12 (μ g/ml) h, and Cmax is 71.78 ± 1.76 μ g/ml, and Tmax is 1.08 ± 0.20h.Compare with Radix Salviae Miltiorrhizae Tabellae, Tmax significant prolongation, the Cmax of salvianolic acid B enteric controlled release tablets significantly reduces under same dose, and AUC enlarges markedly, and its relative bioavailability is 188.2%, and bioavailability is greatly improved.Release in vitro curve in conjunction with the salvianolic acid B enteric controlled release tablets shows that the salvianolic acid B enteric controlled release tablets does not discharge under one's belt, and certain controlled-release effect is arranged in intestinal, and blood drug level is comparatively steady, can better guarantee the lasting effectiveness and the safety of medicine of the present invention.
Claims (11)
1, enteric controlled-release preparation, it comprises the medicine label that comprises active medicine, is wrapped in medicine label outer semi permeability film coating that has aperture and outermost enteric coating.
2, preparation according to claim 1 is characterized in that described medicine label is made up of 20-70 weight portion active medicine, 50-250 weight portion filler, 1-120 weight portion osmotic pressure promoter, 1-20 weight portion binding agent and 0.1-20 weight portion lubricant; The semi permeability film coating is made up of 3-15 weight portion semipermeable membrane coating material and 1 weight portion plasticizer; Enteric coating is made up of 35-65 weight portion enteric-coating material, 10-35 weight portion plasticizer, 5-15 weight portion surfactant and 10-25 weight portion antiplastering aid.
3, preparation according to claim 1 and 2, the weight proportion of its Chinese medicine label and semi permeability film coating sum and enteric coating is 1: 0.05-0.2 is preferably 1: 0.08-0.15.
4, preparation according to claim 1 and 2, medicine label wherein and the film-coated weight proportion of semi permeability are 1: 0.02-0.1 is preferably 1: 0.03-0.05.
5, preparation according to claim 1 and 2, wherein:
Osmotic pressure promoter in the medicine label is selected from any one or more than one the mixture in potassium chloride, sodium chloride, magnesium chloride, potassium sulfate, sodium sulfate, the magnesium sulfate;
Filler in its Chinese medicine label is selected from any one or more than one the mixture in microcrystalline Cellulose, dextrin, starch and derivant thereof, mannitol, sorbitol, lactose, the sucrose;
Binding agent in its Chinese medicine label is selected from any one or more than one the mixture in the mixed solution of polyvidone, methylcellulose, sodium carboxymethyl cellulose, carboxylic propyl methocel, water, water and alcohol; And/or
Lubricant in its Chinese medicine label is a magnesium stearate.
6, preparation according to claim 1 and 2, its Chinese medicine label is made up of 20-70 part salvianolic acid B, 50-250 part microcrystalline Cellulose, 1-50 part lactose, 1-120 part sodium chloride, 1-20 part 30 POVIDONE K 30 BP/USP 30 and 0.1-20 part magnesium stearate;
Preferably form by 20-50 part salvianolic acid B, 80-120 part microcrystalline Cellulose, 20-40 part lactose, 20-100 part sodium chloride, 1-15 part 30 POVIDONE K 30 BP/USP 30 and 1-10 part magnesium stearate;
Preferably by 20-30 part salvianolic acid B, 95-105 part microcrystalline Cellulose, 28-32 part lactose, 58-62 part sodium chloride, 5-7 part 30 POVIDONE K 30 BP/USP 30 and 0.5-2 part magnesium stearate;
Preferably form by 22.5 parts of salvianolic acid Bs, 101 parts of microcrystalline Cellulose, 30 parts of lactose, 60 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 1 part of magnesium stearate.
7, preparation according to claim 1 and 2, wherein:
Coating material in the semi permeability film coating is selected from any one or more than one the mixture of cellulose acetate, ethyl cellulose, cellulose propionate, Merlon, polyethylene, polyvinyl alcohol, vinylacetate etc.;
Plasticizer in the semi permeability film coating is selected from any one or more than one the mixture of phthalate, glyceride, succinate, benzoate, phosphate ester, adipate ester, tartrate, polyethylene glycols etc.;
Plasticizer in the semi permeability film coating is selected from polyethylene glycol 1500 or Macrogol 4000 or its combination; And/or
Wherein the semi permeability film coating is made up of 3-15 part cellulose acetate and 1 part of polyethylene glycol 1500, preferably form by 3-12 part cellulose acetate and 1 part of polyethylene glycol 1500, more preferably form, most preferably form by 4 parts of cellulose acetate and 1 part of polyethylene glycol 1500 by 3-5 part cellulose acetate and 1 part of polyethylene glycol 1500.
8, preparation according to claim 1 and 2, wherein:
Enteric-coating material in the enteric coating is selected from any one or more than one the mixture in acrylic resin I, II, III number;
Plasticizer in the enteric coating is selected from any one or more than one the mixture in liquid paraffin, triethyl citrate, o-benzoic acid diethylester, acetic acid monoglyceride, Oleum Ricini, certain herbaceous plants with big flowers two dibutyl phthalates, the oleic acid;
Surfactant in the enteric coating is selected from any one or more than one the mixture of Tweens, spans, monovalence ammonium amine soap apoplexy due to endogenous wind;
Surfactant in the enteric coating is selected from tween 80; And/or
Antiplastering aid in the enteric coating is selected from any one or more than one the mixture in Pulvis Talci, the Kaolin.
9, preparation according to claim 1 and 2, wherein enteric coating is made up of 35-65 part acrylic resin I number, 5-15 part liquid paraffin, 1-10 part o-benzoic acid diethylester, 5-15 part Oleum Ricini, 5-15 part tween 80 and 10-25 part Pulvis Talci; Preferably form by 40-55 part acrylic resin I number, 8-13 part liquid paraffin, 2-6 part o-benzoic acid diethylester, 8-13 part Oleum Ricini, 8-13 part tween 80 and 14-18 part Pulvis Talci; More preferably form by 42-48 part acrylic resin I number, 11-13 part liquid paraffin, 3-5 part o-benzoic acid diethylester, 11-13 part Oleum Ricini, 11-13 part tween 80 and 13-17 part Pulvis Talci; Most preferably form by 45 parts of acrylic resin I numbers, 12 parts liquid paraffin, 4 parts of o-benzoic acid diethylesters, 12 parts of Oleum Ricini, 12 parts of tween 80s and 15 parts of Pulvis Talci.
10, be used for preparing the method for each described preparation of claim 1-9, it may further comprise the steps:
(1) preparation medicine label: get active medicine, filler, osmotic pressure promoter and the binding agent of described proportioning, mix homogeneously is granulated, and adds the lubricant of described proportioning again, mixing, and tabletting promptly makes the medicine label that contains active medicine;
(2) preparation semi permeability film coating liquid: get the semipermeable membrane coating material and the plasticizer of described proportioning, mix homogeneously, it is 4-20 that adding is preferably volume ratio in right amount: 1 the acetone-water solution or the coating solvent of acetone-alcoholic solution, mixing, it is standby to make coating solution;
(3) semi permeability film coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, and coating makes coated tablet, and coated tablet is dry under 30-60 ℃ of condition, obtains exsiccant coated tablet;
(4) punch: go on foot in (3) with laser or additive method and beat the aperture that one or more, a preferred diameter is 0.2-1.0mm, preferred 0.4-0.8mm on the exsiccant coated tablet that makes;
(5) preparation enteric coating liquid: get described enteric-coating material with an amount of preferably be that 95% alcoholic acid coating solvent soaking dissolves, add described plasticizer, surfactant and antiplastering aid, stirring, mixing, filtration make coating solution;
(6) enteric coating: the enteric coating liquid that the medicine semi permeability thin membrane coated tablet that makes of (4) step and (5) step are made places coating pan, and coating makes coated tablet, and coated tablet is dry under 30-60 ℃ of condition, obtains exsiccant coated tablet.
11, according to described preparation of claim 1-9 or method according to claim 11, it is characterized in that: described active medicine is a salvianolic acid B.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810147260A CN101658508A (en) | 2008-08-25 | 2008-08-25 | Novel enteric controlled-release tablet preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810147260A CN101658508A (en) | 2008-08-25 | 2008-08-25 | Novel enteric controlled-release tablet preparation and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101658508A true CN101658508A (en) | 2010-03-03 |
Family
ID=41786913
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810147260A Pending CN101658508A (en) | 2008-08-25 | 2008-08-25 | Novel enteric controlled-release tablet preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101658508A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670547A (en) * | 2011-03-14 | 2012-09-19 | 北京天衡药物研究院 | Tolterodine tartrate osmotic pump controlled release tablet |
| CN109453132A (en) * | 2018-12-31 | 2019-03-12 | 正大青春宝药业有限公司 | A kind of time lag Dospan and preparation method thereof for treating coronary heart disease |
-
2008
- 2008-08-25 CN CN200810147260A patent/CN101658508A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670547A (en) * | 2011-03-14 | 2012-09-19 | 北京天衡药物研究院 | Tolterodine tartrate osmotic pump controlled release tablet |
| CN109453132A (en) * | 2018-12-31 | 2019-03-12 | 正大青春宝药业有限公司 | A kind of time lag Dospan and preparation method thereof for treating coronary heart disease |
| CN109453132B (en) * | 2018-12-31 | 2021-04-16 | 正大青春宝药业有限公司 | Time-lag controlled-release tablet for treating coronary heart disease and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4557424B2 (en) | Controlled release oral tablets with unit core | |
| EP3854400A1 (en) | Tofacitinib oral sustained release dosage forms | |
| FR2892634A3 (en) | Oral dosage form useful for treating pain comprises an opioid and a dosing structure that provides extended release of the opioid in the presence of alcohol | |
| CN101732276B (en) | Tablet of isosorbide mononitrate | |
| DE2336218B2 (en) | New oral dosage form and process for their production | |
| KR20100014629A (en) | Modified dosage forms of tacrolimus | |
| WO2007016388A2 (en) | Liquid formulations for controlled delivery of benzisoxazole derivatives | |
| US20120251588A1 (en) | Coating Composition, Solid Preparation Coated Therewith, and Method for Preparing Solid Preparation | |
| DE3812799A1 (en) | ORGANIC PREPARATION FOR THE PURPOSES OF AN ACTUATED ACTIVE INGREDIENTS AND METHOD OF PREPARING THEM | |
| CN102048701B (en) | Pitavastatin calcium enteric sustained-release micropill preparation and preparation method thereof | |
| CN105878204A (en) | Metformin hydrochloride osmotic pump controlled release tablet and preparation method thereof | |
| HRP20040945A2 (en) | Sustained release pharmaceutical preparations and methods for producing the same | |
| DE69816624T2 (en) | ADMINISTRATION FORM FOR SERTRALIN WITH DELAYED ACTIVE SUBSTANCE RELEASE | |
| CN104414992B (en) | Glipizide osmotic pump controlled release tablet and preparation method thereof | |
| CN104490838B (en) | A kind of matrix type slow-release tablet agent and its preparation method and application | |
| CN103550183B (en) | A kind of Trimetazidine Hydrochloride osmotic pump controlled release tablet and preparation method thereof | |
| CN101095681A (en) | Alfuzosin Hydrochloride permeating pump type controlled-release preparation and method for preparing the same | |
| CN101658508A (en) | Novel enteric controlled-release tablet preparation and preparation method thereof | |
| CN102349880B (en) | Isradipine controlled-release tablets and preparation method thereof | |
| CN101342151A (en) | Isosorbide mononitrate osmotic pump type controlled release formulation and preparation method thereof | |
| CN101352425A (en) | Compound osmotic pump controlled release preparation and preparation method thereof | |
| CN103284974B (en) | Benzene ring nonyl ester double-layer osmotic pump controlled-release tablet and preparation method thereof | |
| CN101342164B (en) | Bezafibrate controlled release formulation and preparation method thereof | |
| CN110917167A (en) | Ticagrelor enteric sustained-release soft capsule and preparation method thereof | |
| CN100463676C (en) | Control releasing venlafaxine hydrochloride tablet and its prepn |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100303 |