CN1583045A - Composite glycyrrhizae preparation and its preparing method - Google Patents
Composite glycyrrhizae preparation and its preparing method Download PDFInfo
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Abstract
A Chinese medicine in the form of tablet or capsule for treating the cough and sputum caused by respiratory tract infection is prepared from liquorice extract, opium powder, camphor and anise oil.
Description
Technical field: the present invention relates to a kind of compound licorice medicine preparation and preparation method thereof, belong to the field of drug technique.
Background technology: cough caused, the abundant expectoration of treatment respiratory tract infection is a frequently-occurring disease, and commonly encountered diseases is prevented and treated purpose in order to reach, and a large amount of research has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; As the product FUFANG GANCAO PIAN of going on the market is a kind of antitussive preferably, but this medicine has and draws moist and volatility; Easily the moisture absorption is rotten in storage process, and effective ingredient such as Oleum Anisi Stellati, Camphora easily scatter and disappear; Contain opium in the sheet simultaneously, have off-odor, mouthfeel is poor; Disintegrative, bioavailability are poor, and dosage form is single, and application surface is little, are suitable for crowd's narrow range.And number of patent application is 03119520.2, and name is called the product of " FUFANG GANCAO PIAN and preparation method thereof " for solving the bad problem of product mouthfeel in the prior art, and the way of taking to add a large amount of adjuvants is handled; Though certain effect is arranged, new problem is: owing to added a large amount of adjuvants, influenced the speed that absorbs of medicine, increased dose, the patient has absorbed the additive of a lot of no therapeutical effect when taking this product; Especially used a large amount of sucrose, lactose, diabetics should not be taken.Although, have above-mentioned new problem in actual use so these products can be treated the disease of being narrated.For this reason, need to seek a kind ofly have excellent curative again, mouthfeel is good, does not have the product formulation of bad mouthfeel to satisfy patient's demand when taking.
Summary of the invention: the object of the invention is to provide a kind of compound licorice medicine preparation and preparation method thereof.The applicant is by a large amount of experiments, and the clathrate of preparation Oleum Anisi Stellati, Camphora adopts spray-drying process, the film-coated technique film-making, and prepared product moisture resistance is wet, anti-volatile performance obviously strengthens, and stability improves a lot, good mouthfeel; In the present invention, the soft capsule of preparation forms drug blockage in soft gel coat, solved the volatile ingredient instability, medicine is met damp and hot problem of unstable, can also cover adverse drug taste, abnormal smells from the patient, can play the effect that increases stability, improves bioavailability and taste masking; Dispersible tablet provided by the invention, micropill disintegrative are good, and the bioavailability height is particularly suitable for infant, old people and swallow tablet or the inconvenient patient of capsule take.The applicant also provides the method for preparing sugar-free granule, oral liquid simultaneously, and Shai Xuan correctives has high sugariness by experiment, low heat energy, good taste, avirulence and the characteristics such as side effect of not having sucrose have enlarged the use crowd of this product, and are particularly suitable to diabetics, child.The present invention selects tablet, capsule, soft capsule, oral liquid, drop pill, pill, medicated wine, extractum for use, and ejection preparation comprises: common injection, injectable powder, lyophilized injectable powder, infusion solution, other special preparations; Comprise sustained-release preparation.The dose of tablet is little, and dosage is accurate, swallows conveniently, and the content content difference is little, steady quality, and some easy oxidation deterioration and deliquescent medicine can be protected by coating, and light, air, moisture etc. are less to its influence; Oral liquid absorbs fast, the bioavailability height, and the use crowd is wide; Capsule can be covered uncomfortable bitterness, is beneficial to and takes, and light tight capsule can make medicine not be subjected to the influence of oxygen, light in dampness and the air with packaging material preferably, thereby improves stability of drug; Injection bioavailability height, onset speed is fast, no first pass effect, be applicable to can not be oral the patient; Sustained-release preparation is easy to use, provides balance persistent effective blood drug concentration, needing to be particularly useful for the patient of long-term prescription.And this product do not adopt sucrose, lactose, and good mouthfeel is particularly suitable to diabetics.
The present invention constitutes like this: a kind of compound licorice medicine preparation, according to weight proportion: it is by with Radix Glycyrrhizae extractum powder 100～120g, powdered opium 2～6g, Camphora 1～4g, Oleum Anisi Stellati 1～3g, sodium benzoate 1～3g is prepared into tablet, dispersible tablet, capsule, soft capsule, oral liquid, pellet, drop pill, pill, medicated wine, extractum, ejection preparation; Comprise: common injection, injectable powder, lyophilized injectable powder, infusion solution, other special preparations; Comprise sustained-release preparation, membranous patch, gel.Say accurately: prepared preparation is tablet (coated tablet), capsule, oral liquid (Sugarless type), granule (Sugarless type), dispersible tablet, pellet, soft capsule.
Preparation method of the present invention is: get the Radix Glycyrrhizae extractum that routine techniques makes, add sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati prepare clathrate, prepare different preparations by diverse ways again.
Granule of the present invention prepares like this: extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to the mixed-powder (clear paste: soluble starch: cyclamate=3: 2: 0.30) of cyclamate, (air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa); Camphora, Oleum Anisi Stellati and β-CD (1: 9) adopt colloid milling, grind 90min in the time of 60 ℃, get clathrate, add mixing in the granule, drying, and granulate, promptly.
Capsule of the present invention prepares like this: extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to carboxymethyl starch sodium (clear paste: make granule (air quantity: 15～30m/s on powder carboxymethyl starch sodium=7: 3), liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa); Camphora, Oleum Anisi Stellati and β-CD (1: 9) adopt colloid milling, grind 90min in the time of 60 ℃, get clathrate, add mixing in the granule, drying, and granulate incapsulates, promptly.
Tablet of the present invention prepares like this: extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to the powder (clear paste: make granule (air quantity: 15～30m/s carboxymethyl starch sodium=4: 1) of carboxymethyl starch sodium, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa); Camphora, Oleum Anisi Stellati and β-CD (1: 9), adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add mixing in the granule, dry, granulate, tabletting, (the coating solution speed of spraying into is 230～250g/min to the bag film-coat, inlet temperature is for being controlled between 85～88 ℃, and pot body rotating speed is controlled at 5～8r/min; Coating solution: stomach dissolution type polyacrylic acid resin emulsion 120mL,, starch 90g, LHPC12g, tween 80 6g, Pulvis Talci 30g adds water 800ml), promptly.
Dispersible tablet of the present invention prepares like this: extracting liquorice extractum, and drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati and β-CD (1: 9) adopt colloid milling, grind 90min in the time of 60 ℃, get clathrate and add mixing in the extract powder, add 6% microcrystalline Cellulose, and 2.5% carboxymethylstach sodium is crossed 120 mesh sieve mixings respectively, with 1% 30 POVIDONE K 30 BP/USP
30, alcoholic solution is a binding agent system soft material, granulates, and 60 ℃ of dryings, granulate adds 0.15% magnesium stearate, selects lower punch power 19.9929Mpa, remaining die wall power 29.718Mpa, maximum die wall power 15.6494Mpa, maximum upper punch displacement 56.13m * 10
-3Carry out tabletting, promptly get dispersible tablet.
Soft capsule of the present invention prepares like this: extracting liquorice extractum, and drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati spray in the mixed-powder, and 3% PEG400 that adds 50 times of amounts is a substrate, mixing, and capsule material prescription is gelatin: glycerol: water=2: 1: 1, pill, promptly.
Pellet of the present invention prepares like this: extracting liquorice extractum, and drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati and β-CD (1: 9), adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add mixing in the extract powder, press extract powder: citric acid: micropowder silica gel: microcrystalline Cellulose=100: 1: 0.1: 45, with extract powder and citric acid, micropowder silica gel, the microcrystalline Cellulose mixing that sieves, add suitable quantity of water and make soft material, (aperture 0.9mm) is extruded into fine strip shape through the extruder sieve plate, extruding rotating speed is 300r/min, put in the spheronizator, round as a ball rotating speed is 1000r/min, and the round as a ball time is 4min, take out micropill in 50 ℃ of drying 3～4h, promptly.
Oral liquid of the present invention prepares like this: extracting liquorice extractum adds sodium benzoate, powdered opium; Camphora, Oleum Anisi Stellati and β-CD (1: 9) adopt colloid milling, grind 90min in the time of 60 ℃, get clathrate, add extractum, add 0.8% stevioside, mixing, and the distilled water of adding certain volume, promptly.
Among the present invention: opium is brought into play antitussive effect by oral cavity, Sublingual, respiratory mucosa; Radix Glycyrrhizae fluidextract cough-relieving, the coordinating the actions of various ingredients in a prescription that reduces phlegm can cover on the pharyngeal mucosa of inflammation, play the effect of protection mucosa, reduce the suffered stimulation of local sensory nerve ending; Camphora and Fructus Anisi Stellati, the former acrid in the mouth, heat have slight local anesthesia, wind dispelling effect, easily dissolved, and slight phlegm-dispelling functions arranged, for gastrointestinal tract mucous stimulation arranged, make stomach bask, comfortable, latter's acrid-sweet flavor, temperature, it is about 1% to contain volatile oil, mainly contains anisaldehyde, methoxybenzene, and entering respiratory tract can stimulate glandular secretion, reach the effect of dilution sputum rapidly, and the Fructus Foeniculi effect that has warming YANG, cold expelling, regulate the flow of vital energy.The Chinese and Western coupling, Synergistic.
Compared with prior art, the applicant prepares the clathrate of Oleum Anisi Stellati, Camphora by a large amount of experiments, has improved the stability of volatile ingredient, strengthens its dissolubility in oral liquid, has improved the product curative effect; The application adopts film-coated technique, and the tablet moisture resistance of gained is wet, anti-volatile performance obviously strengthens, and stability improves a lot, good mouthfeel, and the process conditions of screening gained have solved the difficulty of disintegrative difference; Capsule of the present invention has not only been covered disagreeable taste, and the applicant screens by experiment, and adopting spray-drying process technology and carboxymethyl starch sodium is adjuvant (clear paste: carboxymethyl starch sodium=7: 3) solved disintegrative, the wet problem of moisture resistance; Soft capsule of the present invention with drug blockage in gelatin: glycerol: in the soft gel coat of water=make at 2: 1: 1, solve medicine and met damp and hot problem of unstable, can also cover adverse drug taste, abnormal smells from the patient, can play the effect that increases stability, improves bioavailability and taste masking, product dissolubility, the disintegrative of gained are good; It is adjuvant and appropriate processing condition that pellet of the present invention adopts 1% citric acid, 0.1% micropowder silica gel, 45% microcrystalline Cellulose, and good product mobility, the plasticity that makes is good, be easy to molding, bioavailability height; Dispersible tablet of the present invention has been selected 6% microcrystalline Cellulose for use, 2.5% carboxymethylstach sodium, 0.15 magnesium stearate and lower punch power 19.9929Mpa, remaining die wall power 29.718Mpa, maximum die wall power 15.6494Mpa, maximum upper punch displacement 56.13m * 10
-3Carry out tabletting, the product that makes is disintegrate fully in the 3min in 19 ℃～21 ℃ water,
Suspension ability is good, bioavailability height, dispersed homogeneous degree be good; The applicant has also developed granule, the oral liquid of Sugarless type, and Shai Xuan correctives sweetness have high sugariness by experiment, low heat energy, and good taste, avirulence and the characteristics such as side effect of not having sucrose, this product is particularly suitable to diabetics.What the present invention was more successful has carried out changing agent with the existing product preparation; The product good mouthfeel that obtains, supplementary product consumption is less.The applicant also finds in development process: preparation provided by the invention also can be used for treating digestive system disease and hepatitis, have effect such as eliminating inflammation and expelling toxin.
The applicant carries out a series of experiments, and is effectively controlled to confirm method provided by the invention, the preparation good effect.
Experimental example 1: to the mice antitussive action
Preparation of the present invention is divided into 6 groups to the antitussive action mice of mice by body weight, and 10 every group, male and female half and half, gastric infusion or after 1 hour, put into 980 type ultrasound atomizer (volumes: 34 * 22 * 26cm with the volume normal saline
3) accept spraying, spray into ammonia (25%) 30s after, take out mice immediately, the cough number in the record mice 3min.
Group Mus number (only) dosage (g/kg) cough number of times (3min)
Matched group 10 16.10 ± 954
FUFANG GANCAO PIAN group 10 4 7.05 ± 6.05
Tablet group 10 4 5.08 ± 4.31 of the present invention
Granule group 10 4 5.11 ± 4.20 of the present invention
Capsule group 10 4 5.23 ± 3.14 of the present invention
Oral liquid group 10 4 5.03 ± 2.56 of the present invention
The result shows: preparation of the present invention is to there being tangible antitussive action to mice, curative effect is not less than the FUFANG GANCAO PIAN group.
Experimental example 2: the preventive and therapeutic effect that carbon tetrachloride is caused hepatic fibrosis in mice
Experimental technique: 40 of regular grade Kunming kind white mice, body weight 20～22g, ♀ ♂ half and half, be divided into 4 groups at random by the body weight principle of reciprocity, 10 every group, ♀ ♂ half and half, sub-cage rearing, the A group is given NS10ml/kg sc, and first dose doubles, injection in 5 days 1 time, continuous 5 weeks, give NS10ml/kg after the injection and irritate stomach, once a day, continuous 6 weeks; B group is given volume fraction and is 40% CCl
4Peanut oil solution is pressed 10ml/kg sc, and first dose doubles, injection in 5 days 1 time, and continuous 5 weeks, give NS after the injection and irritate stomach by 10ml/kg, once a day, continuous 6 weeks; The C group gives CCl by the B group with method
4The 0.01g/L colchicine solution is given by 0.01mg/kg in the back; The D group is pressed the B group with method injection CCl
4Oral liquid of the present invention is given by 100mg/kg in the back.Observe and respectively organize mice feed, drinking-water, activity and fur situation of change every day in experimentation, weighed 1 time in 7 days, in the CCl that all stopped using in the 5th week
4, continue 1 week of administration, to pluck eyeball respectively on the 2nd day after the last administration to get blood, separation of serum is made biochemical analysis.
Observation index and assay method are 1. to the observation of white mice ordinary circumstance and body weight.2. detect serological index, LW=liver weight/body weight * 10 reitman-frankel methods are measured the activity of ALT (glutamate pyruvate transaminase), AST (glutamic oxaloacetic transaminase, GOT), and biuret method measures serum T B (total protein) and the bromocresol green method is measured serum ALB (albumin) content.
Ordinary circumstance and body weight change behind the mice chronic hepatic injury (x ± s, n=10, g)
The 6th week of the 5th week the 4th week the 3rd week the 2nd week the 1st week of body weight before the group experiment
A 20.4±1.4 24.3±1.8 29.5±4.9 31.7±5.1 31.0±5.3 33.1±6.0 34.1±6.1
B 21±1.6 20.4±1.9 26.7±4.7 27.8±3.4 28.9±2.5 28.1±1.8 28.5±1.8
C 21±1.1 21.4±1.3 26.4±2.3 26.7±2.3 26.9±2.8 30.2±4.1 33.6±3.4
D 21±1.0 19.9±2.0 26.4±2.5 27.5±3.0 30.0±5.1 31.7±4.1 33.5±5.3
2 dead mouses of B group only in the experiment.CCl
4The body weight of contamination 1 week back B, C, D3 treated animal all obviously alleviates than the A group, and the B group is obviously low than A, C, D3 group to the 6th all body weight, and the body weight of two groups of C, D is light unlike the A group, so think that two kinds of medicines are to reduction CCl
4Toxicity have certain effect.
Oral liquid of the present invention is to CCl
4The influence of serum biochemical indicator behind the mouse liver injury (x ± s, n=10)
Group LW/g/g ALT/IU AST/IU TP/gL A1b/gL
A 0.41±0.07 53.9±12.6 82.1±16.0 51.3±5.8 24.8±2.7
B 0.73±0.08 110.9±16.3 98.1±11.2 64.9±9.08 17.1±3.01
C 0.51±0.13 75.9±9.28 90.0±19.1 53.1±11.7 22.0±1.21
D 0.49±0.07 64.9±5.01 79.8±16.8 53.0±8.77 22.5±1.92
The serum biochemistry index variation of hepatic fibrosis shows as LW, ALT, AST, TP all raise, and Alb descends, and this experiment shows that oral liquid of the present invention can obviously improve CCl
4Serum biochemical indicator behind the mouse liver injury is handed over property, necrosis and degree of hepatic fibrosis all to have with seasonal disease inspection discovery liver cell and is obviously alleviated, illustrated that oral liquid of the present invention has certain preventive and therapeutic effect to hepatic fibrosis.
Experimental example 2: moulding process screening
In preparation process, whether moulding process proper direct quality and the clinical application effect that influences preparation, and the applicant attempted many different adjuvants, obtained different results; The applicant therefrom selects the technology that can instruct suitability for industrialized production; For this reason, the applicant has carried out a series of experiments to obtain this technology.
(1) Benexate Hydrochloride (Study on Preparation of β-CD)
1. orthogonal experiment selection process
Saturated water solution method is got 30g β-CD, adds a certain amount of distilled water, is mixed with saturated solution under set point of temperature, slowly quantitatively drips volatile oil, the insulated and stirred certain hour makes into hybrid state, cold preservation 24h, sucking filtration, get white depositions, clean with petroleum ether, drying, promptly.
Supercritical ultrasonics technology is got 30g β-CD and is made saturated solution under the set point of temperature, quantitatively drips volatile oil, puts in the ultrasonic cleaner supersound process in required time, cold preservation 24h, and sucking filtration cleans with petroleum ether, drying, promptly.
Colloid milling is got 30g β-CD and is put in the colloid mill, adds an amount of distilled water, slowly adds quantitative volatile oil under set point of temperature, grind in required time, and cold preservation 24h, sucking filtration cleans with petroleum ether, drying, promptly.
Orthogonal experiment is according to the preliminary experiment result, determines ratio, inclusion method, the enclose temperature of volatile oil and beta-schardinger dextrin-, the level of enclose time Several Factors, presses L18 (3
7) orthogonal table experiment, with inclusion rate as investigating index.
The factor level table
Horizontal A B C D E F G
Oil: beta cyclodextrin enclose method temperature/℃ time/min
11: 8 saturated solution methods 40 30
21: 9 ultrasonic methods 50 60
31: 10 colloid millings 60 90
Experimental result
Experiment inclusion rate/% experiment inclusion rate/% experiment inclusion rate/%
1 20.34 7 50.9 13 44.3
2 66.1 8 62.4 14 55.6
3 87.0 9 25.2 15 80.7
4 40.4 10 19.4 16 20.3
5 52.4 11 76.3 17 68.5
6 78.0 12 67.5 18 74.9
The result shows that optimum process condition is A
2B
3E
3F
3, promptly oil is 1: 9 with β-CD ratio, adopts colloid milling, grinds 90min in the time of 60 ℃, also can adopt other types cyclodextrin and process conditions, but technology the best of the present invention.
2. study on the stability
With the naphthalene is internal standard substance, and thiacyclohexane is a solvent, gas Chromatographic Determination Camphora content.
Test 1 group: the tablet of β-CDBao He Camphora, Oleum Anisi Stellati preparation
Test 2 groups: the tablet that does not adopt inclusion technique to make
Camphora mg/ sheet
0 month June of group
Test 1 group 2.0 1.8
Test 2 group 1.7 1.2
The result shows that the present invention adopts beta-cyclodextrin inclusion compound to improve the stability of this product volatile ingredient.
3. oral liquid dissolubility
Test 1 group: the oral liquid of β-CDBao He Camphora, Oleum Anisi Stellati preparation
Test 2 groups: the oral liquid that does not adopt inclusion technique to make
Outward appearance
0 month December of group
Test 1 group and do not have precipitation generation precipitation
Test 2 groups and do not have the generation of precipitation generation nothing precipitation
The result shows that the present invention adopts beta-cyclodextrin inclusion compound, can increase the dissolubility of this product volatile ingredient in oral liquid, obviously improves the quality of products, and then guarantees the clinical efficacy of product.
(2) comparison of granule, tablet, capsule method of granulating
Extrusion granulator: medicine concentrates through extracting, and adjusts relative density, and spray drying obtains fine powder.Add an amount of dextrin, make wetting agent system soft material with ethanol, extrusion granulator is flung to ethanol, 60 ℃ of dryings, granulate, packing.
Dry granulation: medicine is through extracting, concentrating, and the spray-dried fine powder that obtains adds an amount of dextrin, and mix homogeneously is with dry press (pressure 50kg/cm
2, rotating speed 2 changes/min) granulates, and through granulate, getting 20～60 order granules is finished product, packing.
Spray-drying process: medical material is concentrated into relative density through extracting, and with multi-functional dry granulation/coating machine medicine liquid spray is directly formed granule to the dextrin powder, (air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa,) drying, granulate, packing.
Production cost outward appearance fine granularity melting
Extrusion granulator general (++) is (+++) more shallow (++) good (+++) better
That dry-pressing is granulated is higher (+++) relatively poor (+) more shallow (++) be (++) better
Spray-drying process lower (+) relatively poor (+) dark (+) good (+++)
(3) granule, tablet, the screening of capsule drying process with atomizing
1. liquid supply speed screening
The liquid supply speed screening
Charging rate (rpm) dry materials situation
15～20 dried powders
20～25 dry bondings
25～30 materials glue wall
By Biao Kede: charging rate all can obtain dried powder in 45～55ml/min scope, for raising the efficiency, determines that charging rate is at 50～55ml/min.
2. air quantity, the atomizing pressure screening
Air quantity (m/s) atomizing pressure (Pa) dry materials situation
5～10 1.5～2.0 materials glue wall, bonding
15～30 2.5～2.9 dried powders
30～45 3.0～3.5 materials glue wall, bonding
The result shows, the present invention adopts spray-drying process: medical material is through extracting, be concentrated into relative density, with multi-functional dry granulation/coating machine medicine liquid spray is directly formed granule to the dextrin powder, (air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa) made good product performance.
(4) moulding process screening
1. the preparation of Sugarless type oral liquid
Correctives consumption % mouthfeel outward appearance
--pained dark-brown, clear and bright
Sucrose 40 sweet greasy, little hardship is brown, clear and bright
Brown, the clarification of stevioside 0.5 tasty and refreshing, little hardship
Stevioside 0.8 tasty and refreshing, sweet brown, clarification
Brown, the clarification of cyclamate 0.5 tasty and refreshing, little hardship
Brown, the clarification of cyclamate 0.8 tasty and refreshing, little hardship
The result shows that the correctives that the applicant screens by experiment has high sugariness, low heat energy, and good taste, avirulence and the characteristics such as side effect of not having sucrose, this product is particularly suitable to diabetics.
Experimentize by used adjuvant kind, spray drying is made granule, observes and record preparation situation, checks the quality of the pharmaceutical preparations.
Check disintegration: adopting changes the basket method, and lift disintegration tester, tablet or capsule are got 6 slices/, observes the situation by screen cloth.Percent of pass height then disintegrative is good, more pleasant bulk absorption.
Melting is checked: get granule 10g, add 20 times of hot water, stirred 5 minutes, observe immediately.
2. granule
Prescription clear paste soluble starch cyclamate protein sugar melting mouthfeel
132 0.03 t=15s are tasty and refreshing, sweet
The little hardship of 232 0.03 t＞30s
The little hardship of 331 0.03 t＞30s
Tasty and refreshing, the little hardship of 431 0.03 t=20s
531 0.02 t=25s are tasty and refreshing, sweet
631 0.03 t=20s are tasty and refreshing, sweet
The result shows that the product that the correctives cyclamate that the applicant screens by experiment makes has high sugariness,, good, the low heat energy of melting, good taste, avirulence and the characteristics such as side effect of not having sucrose, this product is particularly suitable to diabetics.
3. capsule
Supplementary product consumption (clear paste: disintegration (min) adjuvant)
Carboxymethyl starch sodium 7: 3 15
Carboxymethyl starch sodium 7: 2 20
Carboxymethyl cellulose 7: 3 25
Carboxymethyl cellulose 7: 2 30
Dry starch 7: 3 32
Dry starch 7: 2 28
The result shows, the adjuvant that the applicant screens by experiment: carboxymethyl starch sodium, consumption are clear paste: adjuvant=prepared capsule disintegrative was good in 7: 3.
4. the different film coating procedure of tablet
Parameter process 1 technology 2 technologies 3 technologies 4
Flow velocity (g/min) 120-140 150-180 230-250 270-300
Inlet temperature (℃) 95-98 88-90 85-88 83-85
Pot body rotating speed (r/min) 2-4 4-6 5-8 7-10
The coating time (min) 300 215 195 150
Water content (%)
Time (moon) technology 1 technology 2 technologies 3 technologies 4
0 2.13 2.38 2.52 2.75
3 6.65 5.16 3.43 3.96
Dissolution (%)
Time (moon) technology 1 technology 2 technologies 3 technologies 4
0 90.1 85.6 80.9 68.8
3 62.8 68.3 75.8 61.9
The result shows, the film coating procedure that the applicant screens by experiment, be that the coating solution speed of spraying into is 230～250g/min, inlet temperature is for being controlled between 85～88 ℃, it is good that pot body rotating speed is controlled at the product dissolution that 5～8r/min makes, presentation quality is stable, and water content is little, and the moisture resistance performance is good.
5. soft capsule: the formulation characteristic of soft capsule has determined that the powder charge thing is isolated from the outside in the capsule shells, and can soft capsule produce bioavailability preferably, depend on oral after disintegrate in time.So the applicant studies screening capsule material by experiment and has solved the problem of this product disintegrate.
The applicant is index with the lemon yellow, adopting dissolution determination method is index with the rate of dissolution, and the change of having investigated gelatin, glycerol ratio is to add the influence to the softgel shell rate of dissolution such as macromolecular material.Capsule psychological treatment liquid is extract powder: the mixed liquor of 3% PEG400=1: 50; The preparation of softgel shell: take by weighing the lemon yellow of recipe quantity,, in the lemon yellow aqueous solution, soak 36h, be lower than 45 ℃ of following heating and make it to dissolve about 3min, add glycerol again to stir with the recipe quantity gelatin with the suitable quantity of water dissolving, standby.To make capsule psychological treatment liquid and 60 ℃ of gelatin solutions are pressed into ball with rolling capsule machine.The solidifying by cooling in wind molding is with petroleum ether flush away surface oil reservoir, in 20～32 ℃ of hot air dryings, promptly.Rate of dissolution is measured: get above-mentioned prescription precision and weigh, adopt changeing the basket method, is dissolution medium with the 500ml distilled water, and temperature is (37 ± 0.5) ℃, rotating speed is 30r/min, per minute sampling 1 time, the 5ml that at every turn takes a sample is up to dissolving fully, measure absorbance in wavelength 423nm place, determine the content of lemon yellow, try to achieve different time lemon yellow accumulation meltage, get the rate of dissolution value.Measure rate of dissolution through 40 ℃ of storages once more after 21 days.
The different prescriptions of softgel shell are formed
Prescription gelatin/glycerol/lemon yellow/water/g gelatin/glycerin/water
1 10.0/5/1.11/5.0 2/1/1
2 10.0/10/1.32/5.0 1/1/1
3 10.0/15/1.54/5.0 0.75/1/1
4 10.0/20/1.63/5.0 0.50/1/1
5 100/25/1.72/5.0 0.45/1/1
The rate of dissolution result
Prescription numbers 12345
Rate of dissolution (mg/min) 1.456 1.275 1.384 1.114 0.715
Rate of dissolution after 21 days (mg/min) 0.845 0.217 0.236 0.455 0.162
Capsule material capsule psychological treatment liquid disintegration (min)
Gelatin: glycerol: aqueous extract powder: 0 month March of 3% PEG400
2∶1∶1 1∶50 18 20
1∶1∶1 1∶50 25 28
0.75∶1∶1 1∶50 30 35
0.50∶1∶1 1∶50 26 28
0.45∶1∶1 1∶50 23 25
The result shows, capsule material prescription is gelatin: glycerol: water=2: 1: 1, softgel shell dissolubility, disintegrative are good.
6. dispersible tablet: meet water rapidly disintegrate form the water dispersion tablet of uniform sticky suspension, it is poor to have solved the FUFANG GANCAO PIAN disintegrative, stripping is shortcoming slowly, adopts the dispersible tablet disintegrate fully in the 3min in 19 ℃～21 ℃ water that makes, and suspension ability is good, bioavailability is high, dispersed homogeneous degree.
Adjuvant screening: it is an amount of to take by weighing dry extract, adds diluent, disintegrating agent and crosses 120 mesh sieve mixings in right amount, respectively, with 1% 30 POVIDONE K 30 BP/USP
30, alcoholic solution is binding agent system soft material, granulation, 60 ℃ of dryings, and granulate adds magnesium stearate, tabletting.
The selection result (%)
Prescription dextrin micro crystal cellulose milk sugar carboxymethylstach sodium hyprolose magnesium stearate result
1 6--2.5-0.15 disintegrates are slow, suspendible
2-6---0.15 disintegrates soon, suspendible not
3---2.5-0.15 disintegrates are slow, the suspension sedimentation is fast
4---2.5-0.15 disintegrates are fast, the suspension sedimentation is fast
5--6 2.5-0.15 disintegrates, suspendible not
6--6 1.5 1.5 0.15 disintegrates are fast, suspension is even
7--6-2.5 0.15 disintegrates soon, suspendible not
Group disintegration
FUFANG GANCAO PIAN 25min
Dispersible tablet 45s of the present invention
The result shows, has selected 6% microcrystalline Cellulose, 2.5% carboxymethylstach sodium, and the product disintegrating property that 0.15 magnesium stearate makes is good.
The process conditions screening:
Preparation: use heavy single punch tablet machine, under different pressures, speed tabletting with 82/min, investigate the influence of different lower punch powers, remaining die wall power, maximum die wall power, maximum upper punch displacement to the quality of the sheet that is pressed into, with dispersed homogeneous degree and disintegration time is index, simultaneously the outward appearance of observation post's tabletting.
The mensuration of dispersible tablet dispersed homogeneous degree is got 2 of dispersible tablets of the present invention, places the 100ml distilled water respectively, stirs to make it to disperse fully, and granule should pass through the screen cloth of aperture 710um fully.
The maximum upper punch displacement of the maximum die wall power of the remaining die wall power of experiment lower punch power is uniformly dispersed
The degree disintegration time
Mpa Mpa Mpa m×10
-3
(min)
1 5.8427 19.504 7.4526 54.00 whole screen clothes by 710um
1.6
2 19.9929 29.718 15.6494 56.13 whole screen clothes by 710um
1.5
3 25.8702 31.460 26.9868 60.50 90% screen clothes by 710um
3.1
4 33.9842 37.340 27.7935 65.00 87% screen clothes 4.5 by 710um
The result shows that No. 1 experiment gained sheet rough surface is obvious, and easily dry linting is considered to be worth doing, and No. 2 experiment institute tabletting gained sheets are all by the screen cloth of 710um, and disintegration time is less than 3min, and gloss fineness is good, and No. 3, No. 4 dispersed homogeneous degree does not reach requirement.So select lower punch power 19.9929Mpa, remaining die wall power 29.718Mpa, maximum die wall power 15.6494Mpa, maximum upper punch displacement 56.13m * 10
-3Carry out tabletting.
7. pellet: the micropill diameter is less than 2.5mm, and class is in particle properties, the bioavailability height, and the applicant is when development product micropill of the present invention, and maximum difficulty is exactly that hygroscopicity is strong and mobile poor, and poor plasticity is difficult to molding.Through the screening of following prescription adjuvant, determine that this product extract powder adds adjuvants such as 1% citric acid, 0.1% micropowder silica gel, microcrystalline Cellulose, the ratio of principal agent and adjuvant is 1: 1 o'clock ball yield, angle of repose and pill good uniformity.
Adjuvant screening: take by weighing the medicine and the adjuvant of recipe quantity, and, add an amount of dehydrated alcohol and make wetting agent system soft material with its mix homogeneously, cross 24 mesh sieves and make wet granular, round as a ball in the sugar coating machine (45r/min) that drop into to rotate immediately, and place the dry back of 40 ℃ of baking ovens to take out, cross the screening sample.
Measure angle of repose: adopt the fixed funnel method, funnel is fixed on the graph paper of horizontal positioned, the funnel end opening is 3cm apart from the distance of graph paper, pour the difference pill of writing out a prescription into funnel respectively, below the cone tip that forms up to the bottom touches till the bell mouth, measure the diameter of conical base, calculate not angle of departure (relative humidity=75%).
Homogeneity be the ball between the 18-40 order heavy/total ball is heavy by * 100%, yield P%=W1/W * 100% (wherein the weight W 1 of 18-24 order ball, the gross weight that feeds intake W)
Adjuvant The selection result unit (g/100g extract powder)
Experiment microcrystalline Cellulose starch methylcellulose micropowder silica gel citric acid
1 45 - - 0.1 1.0
2 - 45 - 0.1 1.0
3 60 - - 0.1 1.0
4 - - 45 0.1 1.0
5 30 - - 0.5 0.5
6 - 60 - 0.1 1.0
7 - - 60 0.1 1.0
Experiment yield (%) homogeneity angle of repose (%)
1 62.11 35.46 86.45
2 44.41 40.56 65.23
3 55.92 36.11 79.45
4 57.91 37.67 71.65
5 57.33 36.56 82.60
6 48.95 37.84 68.56
7 51.64 43.23 70.48
The result shows, extract powder: citric acid: micropowder silica gel: microcrystalline Cellulose=100: 1: 0.1: 45 is best prescription, and yield reaches more than 60%, and 18-40 purpose ball reaches more than 85%, and homogeneity is good.
Process conditions screening: preparation flow: with extract powder powder and the adjuvant mixing that sieves, add suitable quantity of water and make soft material, (aperture 0.9mm) is extruded into fine strip shape through the extruder sieve plate, put in the spheronizator, regulate rotating speed and round as a ball time, make granule round as a ball fully, take out micropill in 50 ℃ of drying 3～4h.After the screening, carry out technology assessment with 18～24 purpose micropills.
3 principal elements that round as a ball technology is extruded in influence are: (A) extrude rotating speed; (B) round as a ball rotating speed; (C) the round as a ball time.This experiment is the optimization screening that index is carried out process conditions with the roundness (critical angle φ represents with the plane) and 18～24 purpose yields (f) of micropill.
The mensuration of roundness: a certain amount of micropill is put on the flat board, a dull and stereotyped side is lifted, measure at micropill begin the to roll angle (φ) of top rake plane and horizontal plane, this angle is more little, and the roundness of micropill is good more.
Experiment number extrude the round as a ball rotating speed of rotating speed (r/min) (r/min) round as a ball time (min) 2 φ/°
f/％
1 100 500 2 37.4 55.7
2 200 500 4 37.0 62.9
3 300 800 2 32.8 71.5
4 100 1000 6 38.4 71.2
5 300 1000 4 25.6 89.5
The result shows: extruding rotating speed is 300r/min, and round as a ball rotating speed is 1000r/min, and the round as a ball time is that 4min is the optimum process condition.
The specific embodiment:
Embodiments of the invention 1: Radix Glycyrrhizae extractum powder 100g, powdered opium 2g, Camphora 1g, Oleum Anisi Stellati 1g, sodium benzoate 1g, extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to cyclamate (clear paste: soluble starch: make granule (air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa) on powder cyclamate=3: 2: 0.030); Camphora, Oleum Anisi Stellati and β-CD (1: 9) adopt colloid milling, grind 90min in the time of 60 ℃, get clathrate, add mixing in the granule, drying, and granulate promptly gets granule, instructions of taking: oral, every day 3 times, each 1 bag.
The male example 2 of reality of the present invention: Radix Glycyrrhizae extractum powder 120g, powdered opium 6g, Camphora 4g, Oleum Anisi Stellati 3g, sodium benzoate 3g, extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to carboxymethyl starch sodium (clear paste: make granule (air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa) on powder carboxymethyl starch sodium=7: 3); Camphora, Oleum Anisi Stellati and β-CD (1: 9) adopt colloid milling, grind 90min in the time of 60 ℃, get clathrate, add mixing in the granule, drying, and granulate incapsulates, and promptly gets capsule.Instructions of taking: oral, every day 3 times, each 1-2 grain.
Embodiments of the invention 3: Radix Glycyrrhizae extractum powder 112.5g, powdered opium 4g, Camphora 2g, Oleum Anisi Stellati 2g, sodium benzoate 2g, extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to carboxymethyl starch sodium (clear paste: make granule (air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa) on powder carboxymethyl starch sodium=4: 1); Camphora, Oleum Anisi Stellati and β-CD (1: 9), adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add mixing in the granule, dry, granulate, tabletting, (the coating solution speed of spraying into is 230～250g/min to the bag film-coat, inlet temperature is for being controlled between 85～88 ℃, and pot body rotating speed is controlled at 5～8r/min; Coating solution: stomach dissolution type polyacrylic acid resin emulsion 120mL, cane sugar powder 30g, starch 90g, LHPC12g, lactose 30g, tween 80 6g, Pulvis Talci 30g adds water 800ml), promptly get tablet.Instructions of taking: oral, every day 3 times, each 1-2 sheet.
Embodiments of the invention 4: Radix Glycyrrhizae extractum powder 112.5g, powdered opium 4g, Camphora 2g, Oleum Anisi Stellati 2g, sodium benzoate 2g, extracting liquorice extractum adds sodium benzoate, powdered opium; Camphora, Oleum Anisi Stellati and β-CD (1: 9), the employing colloid milling grinds 90min in the time of 60 ℃, get clathrate, adds extractum, adds 1.5mg/ml Folium Chrysanthemi glycoside, mixing, the distilled water of adding certain volume promptly gets oral liquid.
Embodiments of the invention 5: Radix Glycyrrhizae extractum powder 112.5g, powdered opium 4g, Camphora 2g, Oleum Anisi Stellati 2g, sodium benzoate 2g, extracting liquorice extractum adds sodium benzoate, powdered opium; Camphora, Oleum Anisi Stellati and β-CD (1: 9) adopt colloid milling, grind 90min in the time of 60 ℃, get clathrate, add extractum, splash in the polyvinyl alcohol-4000, promptly get drop pill.
Embodiments of the invention 6: Radix Glycyrrhizae extractum powder 120g, powdered opium 6g, Camphora 4g, Oleum Anisi Stellati 3g, sodium benzoate 3g, extracting liquorice extractum, drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati and β-CD (1: 9), adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add mixing in the extract powder, press extract powder: citric acid: micropowder silica gel: microcrystalline Cellulose=100: 1: 0.1: 45, with extract powder and citric acid, micropowder silica gel, the microcrystalline Cellulose mixing that sieves adds suitable quantity of water and makes soft material, and (aperture 0.9mm) is extruded into fine strip shape through the extruder sieve plate, extruding rotating speed is 300r/min, put in the spheronizator, round as a ball rotating speed is 1000r/min, and the round as a ball time is 4min, take out micropill in 50 ℃ of drying 3～4h, promptly get pellet.
Embodiments of the invention 7: Radix Glycyrrhizae extractum powder 100g, powdered opium 2g, Camphora 1g, Oleum Anisi Stellati 1g, sodium benzoate 1g, extracting liquorice extractum, drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati spray in the mixed-powder, and 3% PEG400 that adds 50 times of amounts is a substrate, mixing, and capsule material prescription is gelatin: glycerol: water=2: 1: 1, pill promptly gets soft capsule.Instructions of taking: oral, every day 3 times, each 1-2 grain.
Embodiments of the invention 8: Radix Glycyrrhizae extractum powder 112.5g, powdered opium 4g, Camphora 2g, Oleum Anisi Stellati 2g, sodium benzoate 2g, extracting liquorice extractum, drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati and β-CD (1: 9) adopt colloid milling, grind 90min in the time of 60 ℃, get clathrate and add mixing in the extract powder, add 6% microcrystalline Cellulose, and 2.5% carboxymethylstach sodium is crossed 120 mesh sieve mixings respectively, with 1% 30 POVIDONE K 30 BP/USP
30, alcoholic solution is a binding agent system soft material, granulates, and 60 ℃ of dryings, granulate adds 0.15% magnesium stearate, selects lower punch power 19.9929Mpa, remaining die wall power 29.718Mpa, maximum die wall power 15.6494Mpa, maximum upper punch displacement 56.13m * 10
-3Carry out tabletting, promptly get dispersible tablet.Instructions of taking: oral, every day 3 times, each 1-2 sheet.
Claims (10)
1, a kind of compound licorice medicine preparation, it is characterized in that: calculate according to weight proportion: it is with Radix Glycyrrhizae extractum powder 100～120g, powdered opium 2～6g, Camphora 1～4g, Oleum Anisi Stellati 1～3g, sodium benzoate 1～3g is prepared into tablet, dispersible tablet, capsule, soft capsule, oral liquid, pellet, drop pill, pill, medicated wine, extractum, ejection preparation; Comprise: common injection, injectable powder, lyophilized injectable powder, infusion solution, other special preparations; Comprise sustained-release preparation, membranous patch, gel.
2, according to the described compound licorice medicine preparation of claim 1, it is characterized in that: prepared preparation is coated tablet tablet, capsule, Sugarless type oral liquid, sugar-free granule, dispersible tablet, pellet, soft capsule.
3, as the preparation method of claim 1,2 described compound licorice medicine preparations, it is characterized in that: get the Radix Glycyrrhizae extractum that routine techniques makes, add sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati prepare clathrate, prepare different preparations by diverse ways again.
4, according to the preparation method of the described compound licorice medicine preparation of claim 3, it is characterized in that: granule prepares like this: extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to clear paste: soluble starch: the mixed-powder of the cyclamate of cyclamate=make at 3: 2: 0.03, the process conditions of spraying are: air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa; Camphora, Oleum Anisi Stellati and β-CD=1: 9, adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add mixing in the granule, drying, granulate, promptly.
5, according to the preparation method of the described compound licorice medicine preparation of claim 3, it is characterized in that: capsule prepares like this: extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to clear paste: make granule on the powder of the carboxymethyl starch sodium of carboxymethyl starch sodium=7: 3; Process conditions wherein are: air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa; Camphora, Oleum Anisi Stellati and β-CD=1: 9, adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add mixing in the granule, drying, granulate incapsulates, promptly.
6, according to the preparation method of the described compound licorice medicine preparation of claim 3, it is characterized in that: tablet prepares like this: extracting liquorice extractum, add sodium benzoate, powdered opium uniform mixing, be sprayed to clear paste: make granule on the powder of the carboxymethyl starch sodium of carboxymethyl starch sodium=4: 1, process conditions are: air quantity: 15～30m/s, liquid supply speed 15～20rpm, atomizing pressure 2.5～2.9Pa; Camphora, Oleum Anisi Stellati and β-CD=1: 9, adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add mixing in the granule, drying, granulate, tabletting, the bag film-coat, its process conditions are: the coating solution speed of spraying into is 230～250g/min, and inlet temperature is for being controlled between 85～88 ℃, and pot body rotating speed is controlled at 5～8r/min; Coating solution: stomach dissolution type polyacrylic acid resin emulsion 120mL, starch 90g, LHPC12g, tween 80 6g, Pulvis Talci 30g adds water 800ml, promptly.
7, according to the preparation method of the described compound licorice medicine preparation of claim 3, it is characterized in that: dispersible tablet prepares like this: extracting liquorice extractum, and drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati and β-CD=1: 9, adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate and add mixing in the extract powder, add 6% microcrystalline Cellulose, 2.5% carboxymethylstach sodium is crossed 120 mesh sieve mixings respectively, with 1% 30 POVIDONE K 30 BP/USP
30, alcoholic solution is a binding agent system soft material, granulates, and 60 ℃ of dryings, granulate adds 0.15% magnesium stearate, selects lower punch power 19.9929Mpa, remaining die wall power 29.718Mpa, maximum die wall power 15.6494Mpa, maximum upper punch displacement 56.13m * 10
-3Carry out tabletting, promptly get dispersible tablet.
8, according to the preparation method of the described compound licorice medicine preparation of claim 3, it is characterized in that: soft capsule prepares like this: extracting liquorice extractum, and drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati spray in the mixed-powder, and 3% PEG400 that adds 50 times of amounts is a substrate, mixing, and capsule material prescription is gelatin: glycerol: water=2: 1: 1, pill, promptly.
9, according to the preparation method of the described compound licorice medicine preparation of claim 3, it is characterized in that: pellet prepares like this: extracting liquorice extractum, and drying is pulverized, and adds sodium benzoate, powdered opium uniform mixing; Camphora, Oleum Anisi Stellati and β-CD=1: 9, adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add mixing in the extract powder, press extract powder: citric acid: micropowder silica gel: microcrystalline Cellulose=100: 1: 0.1: 45, with extract powder and citric acid, micropowder silica gel, the microcrystalline Cellulose mixing that sieves adds suitable quantity of water and makes soft material, is extruded into fine strip shape through the extruder sieve plate, wherein: the hole diameter of sieve (perforated) plate is 0.9mm, extruding rotating speed is 300r/min, put in the spheronizator, round as a ball rotating speed is 1000r/min, and the round as a ball time is 4min, take out micropill in 50 ℃ of drying 3～4h, promptly.
10, according to the preparation method of the described compound licorice medicine preparation of claim 3, it is characterized in that: oral liquid prepares like this: extracting liquorice extractum adds sodium benzoate, powdered opium, Camphora, Oleum Anisi Stellati and β-CD=1: 9, adopt colloid milling, in the time of 60 ℃, grind 90min, get clathrate, add extractum, add 0.8% stevioside, mixing, the distilled water that adds certain volume, promptly.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410022761 CN1583045A (en) | 2004-06-07 | 2004-06-07 | Composite glycyrrhizae preparation and its preparing method |
| CNB2005100782349A CN100482208C (en) | 2004-06-07 | 2005-06-06 | Compound licorice medicine prepn and its prepn process |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410022761 CN1583045A (en) | 2004-06-07 | 2004-06-07 | Composite glycyrrhizae preparation and its preparing method |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100444831C (en) * | 2005-06-03 | 2008-12-24 | 北京正大绿洲医药科技有限公司 | Compound dripping pills of licorice and its preparing process |
| CN114010610A (en) * | 2021-12-24 | 2022-02-08 | 宁波大红鹰药业股份有限公司 | Compound licorice tablet capable of being directly pressed by dry powder process and preparation method thereof |
| CN116392515A (en) * | 2023-05-29 | 2023-07-07 | 弘美制药（中国）有限公司 | Fennel powder inclusion compound and preparation method thereof and stomach-harmonizing bismuth magnesium granule compound preparation |
-
2004
- 2004-06-07 CN CN 200410022761 patent/CN1583045A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100444831C (en) * | 2005-06-03 | 2008-12-24 | 北京正大绿洲医药科技有限公司 | Compound dripping pills of licorice and its preparing process |
| CN114010610A (en) * | 2021-12-24 | 2022-02-08 | 宁波大红鹰药业股份有限公司 | Compound licorice tablet capable of being directly pressed by dry powder process and preparation method thereof |
| CN116392515A (en) * | 2023-05-29 | 2023-07-07 | 弘美制药（中国）有限公司 | Fennel powder inclusion compound and preparation method thereof and stomach-harmonizing bismuth magnesium granule compound preparation |
| CN116392515B (en) * | 2023-05-29 | 2023-08-15 | 弘美制药（中国）有限公司 | Fennel powder inclusion compound and preparation method thereof and stomach-harmonizing bismuth magnesium granule compound preparation |
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