CN105106686A - Clopidogrel hydrogen sulfate compound sustained-release tablet and preparation method thereof - Google Patents
Clopidogrel hydrogen sulfate compound sustained-release tablet and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a clopidogrel hydrogen sulfate compound sustained-release tablet and a preparation method thereof. The compound sustained-release tablet is composed of clopidogrel hydrogen sulfate, honey-fried licorice root, Chinese yam, costus root, eucommia, fortune eupatorium herb, hairyleaf litse fruit, maize, Airentuo, osmanthus fruit, starfish, Chinese chives, high-viscosity hydroxypropyl methylcellulose, low-viscosity hydroxypropyl methylcellulose sodium alginate, starch, powdered sugar, polysorbate and aerosil. The preparation method includes the steps of material preparation, extraction of active pharmaceutical ingredients of traditional Chinese medicine, pelletizing, pellet size stabilization and tabletting. Components of the compound sustained-release tablet has obvious synergistic effect, so that treating effect of clopidogrel hydrogen sulfate is improved, side effect, of clopidogrel hydrogen sulfate, on gastrointestinal tract is avoided, the compound sustained-release tablet has effect of tonifying spleen and stomach, occurrence rate of adverse reaction is lowered, and patient compliance is improved. Efficacy is maintained by controlling concentration, of the tablet, in blood, so that viscera of patients are protected to some extent.
Description
Technical field
The invention belongs to cardiovascular and cerebrovascular vessel medication field, is specifically a kind of bisulfate clopidogrel compound slow-release tablet and preparation method.
Background technology
Bisulfate clopidogrel is white or off-white color crystalline powder; Odorless, dissolves in water, methanol or glacial acetic acid, soluble,very slightly in acetone or chloroform; Almost insoluble in ethyl acetate, dissolve in 0.1mol/L hydrochloric acid solution.Specific optical rotation :+52 ° to+56 °, condition of storage: 2 ~ 8 DEG C.Be mainly used in patient, the Acute Coronary Syndrome Patients for the treatment of myocardial infarction patient (from several days to being less than 35 days), Ischemic Stroke (from 7 days to being less than 6 months) or making a definite diagnosis Peripheral arteral disease.
Within the scope of clopidogrel 50-150mg, major metabolite pharmacokinetics is linear increase (plasma concentration and dose proportional).In very wide concentration range, clopidogrel and major metabolite thereof all can be combined with the plasma protein reversibility of human body (being respectively 98% and 94%) in vitro.After the clopidogrel of human oral 14C labelling, in 5 days, about 50% is discharged by urine, and about 46% is discharged by feces, once with repeat administration after, in blood plasma, the elimination half-life of main metabolites is 8 hours.
Rat and the clinical front modal reaction of baboon are that liver changes.To take dosage be 25 times that human body takes using dosage after 75mg/ days clopidogrels, the change of these livers is the result because medicine affects liver metabolism enzyme.Rat and baboon take high dose clopidogrel, gastric tolerability difference (gastritis, gastric ulcer and/or dizzy).
Summary of the invention
In order to reduce bisulfate clopidogrel to liver and gastrointestinal side effect, improving the compliance of patient, the invention provides a kind of bisulfate clopidogrel compound slow-release tablet and preparation method.This compound slow-release tablet not only increases the therapeutical effect of hydrogen sulfate chlorine than Gray, and overcomes hydrogen sulfate chlorine than Gray to gastrointestinal side effect, has the effect of strengthening the spleen and nourishing the stomach, reduces the incidence rate of untoward reaction, improve patient compliance.
The present invention seeks to be realized by following technical scheme:
A kind of bisulfate clopidogrel compound slow-release tablet, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 10 ~ 20 parts, Radix Glycyrrhizae Preparata 35 ~ 40 parts, Rhizoma Dioscoreae 50 ~ 60 parts, the Radix Aucklandiae 20 ~ 25 parts, the Cortex Eucommiae 35 ~ 40 parts, Herba Eupatorii 20 ~ 25 parts, clear Fructus Solani melongenae 40 ~ 45 parts, Semen setariae 30 ~ 35 parts, Gynura bodinieri Levl. 30 ~ 35 parts, Flos Osmanthi Fragrantis fruit 45 ~ 50 parts, Asterias amurensis Lutken 15 ~ 20 parts, 20 ~ 25 parts, Folium Allii tuberosi, high viscosity hypromellose 10 ~ 15 parts, low-viscosity hypromellose sodium alginate 5 ~ 10 parts, starch 5 ~ 10 parts, Icing Sugar 5 ~ 10 parts, Polysorbate 2 ~ 5 parts, micropowder silica gel 2 ~ 5 parts.
The object of the invention can also be realized by following technical scheme:
A kind of bisulfate clopidogrel compound slow-release tablet, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 10 parts, Radix Glycyrrhizae Preparata 35 parts, Rhizoma Dioscoreae 50 parts, the Radix Aucklandiae 20 parts, the Cortex Eucommiae 35 parts, Herba Eupatorii 20 parts, clear Fructus Solani melongenae 40 parts, Semen setariae 30 parts, Gynura bodinieri Levl. 30 parts, Flos Osmanthi Fragrantis fruit 45 parts, Asterias amurensis Lutken 15 parts, 20 parts, Folium Allii tuberosi, high viscosity hypromellose 10 parts, low-viscosity hypromellose sodium alginate 5 parts, starch 5 parts, Icing Sugar 5 parts, Polysorbate 2 parts, micropowder silica gel 2 parts.
A kind of bisulfate clopidogrel compound slow-release tablet, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 15 parts, Radix Glycyrrhizae Preparata 38 parts, Rhizoma Dioscoreae 55 parts, the Radix Aucklandiae 23 parts, the Cortex Eucommiae 38 parts, Herba Eupatorii 23 parts, clear Fructus Solani melongenae 42 parts, Semen setariae 32 parts, Gynura bodinieri Levl. 33 parts, Flos Osmanthi Fragrantis fruit 48 parts, Asterias amurensis Lutken 17 parts, 23 parts, Folium Allii tuberosi, high viscosity hypromellose 12 parts, low-viscosity hypromellose sodium alginate 8 parts, starch 7 parts, Icing Sugar 6 parts, Polysorbate 3 parts, micropowder silica gel 3 parts.
A kind of bisulfate clopidogrel compound slow-release tablet, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 20 parts, Radix Glycyrrhizae Preparata 40 parts, Rhizoma Dioscoreae 60 parts, the Radix Aucklandiae 25 parts, the Cortex Eucommiae 40 parts, Herba Eupatorii 25 parts, clear Fructus Solani melongenae 45 parts, Semen setariae 35 parts, Gynura bodinieri Levl. 35 parts, Flos Osmanthi Fragrantis fruit 50 parts, Asterias amurensis Lutken 20 parts, 25 parts, Folium Allii tuberosi, high viscosity hypromellose 15 parts, low-viscosity hypromellose sodium alginate 10 parts, starch 10 parts, Icing Sugar 10 parts, Polysorbate 5 parts, micropowder silica gel 5 parts.
Present invention also offers a kind of preparation method of bisulfate clopidogrel compound slow-release tablet, comprise the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of described compound slow-release tablet and parts by weight, wherein bisulfate clopidogrel pulverized 200 mesh sieves, and high viscosity hypromellose, low-viscosity hypromellose sodium alginate, starch, Icing Sugar, Polysorbate, micropowder silica gel pulverized 100 mesh sieves respectively;
2) extraction of raw material of Chinese medicine medicine, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, by raw material of Chinese medicine medicine Radix Glycyrrhizae Preparata, Rhizoma Dioscoreae, the Radix Aucklandiae, the Cortex Eucommiae, Herba Eupatorii, clear Fructus Solani melongenae, Semen setariae, Gynura bodinieri Levl., Flos Osmanthi Fragrantis fruit, Asterias amurensis Lutken, Folium Allii tuberosi adds in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, filtering residue, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, filtering residue is added in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, merge 2 gained filtrates, vacuum concentration obtains concentrated solution to 1/4th of former filtrate volume,
3) granulate, by bisulfate clopidogrel, step 2) gained concentrated solution, amylum pregelatinisatum, mannitol, sucrose ester, sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, wet granulation;
4) granulate, by step 3) gained granule granulate, cross 40 mesh sieves;
5) tabletting, by step 4) gained granule is by high speed tablet press tabletting, and specification is containing clopidogrel hydrogen sulfate 75mg.
The preparation method of a kind of bisulfate clopidogrel compound slow-release tablet of the present invention, can also be realized by following technical scheme:
Described granulation step drying equipment used is fluid bed, and technological parameter is: inlet temperature is 45 ~ 50 DEG C, and temperature of charge is 35 ~ 40 DEG C, and leaving air temp is 30 ~ 35 DEG C.
In order to better play the drug effect of bisulfate clopidogrel and reduce its toxic and side effects, the present invention carries out prescription and craft screening through lot of experiments, selected raw material of Chinese medicine medicine: Radix Glycyrrhizae Preparata, and property is sweet, and taste is put down, GUIXIN, lung, spleen, stomach warp; Spleen reinforcing stomach function regulating, Yiqi and vein recovery, be used for the treatment of weakness of the spleen and stomach, fatigue and weakness, severe palpitation.Rhizoma Dioscoreae, returns spleen, lung, refreshing sword, has and nourishes strong, aid digestion, to hold back sweating due to debility, antidiarrheal effect, be mainly used in insufficiency of the spleen diarrhoea, cough due to deficiency of the lung and dyspeptic chronic enteritis.The Radix Aucklandiae, acrid in the mouth, hardship, warm in nature, return spleen; Large intestine, tri-jiao channel.Cure mainly: promoting the circulation of QI to relieve pain; Intestinal stasis relieving in tune.Main born of the same parents coerce distension foot; Abdominal distention; Tell and have loose bowels; Heavy after dysentery.For weighing after breast gastral cavity distending pain, dysentery, food stagnation does not disappear, anorexia; Middle gas is not economized; Sudden deafness; Snake bite and insect sting; Toothache.The Cortex Eucommiae, acrid in the mouth, flat, return spleen, stomach, kidney channel; Warming middle-JIAO to relieve pain, promoting flow of QI and blood, relieving asthma, diuresis, main coldness and pain in the epigastrium, food stagnation flatulence, regurgitation vomiting, heatstroke vomiting and diarrhoea, dysentery, colic of cold type stomachache, asthma, cold-damp dropsy, dysuria, turbid urine, sore swollen toxin, toothache, arthralgia due to cold-dampnes, traumatic injury.Herba Eupatorii, property is pungent, taste is flat, returns spleen, stomach, lung meridian; Removing dampness by means of aromatics, appetizing of being amusing, delivers expelling summer-heat.For turbid damp obstructing in middle-JIAO, gastral cavity painful abdominal mass vomiting and nausea, sweet greasy in mouth, halitosis, sialism, heat-damp in summer table disease, feeling of fullness in the head is uncomfortable in chest.Clear Fructus Solani melongenae, property is pungent, mildly bitter flavor, returns spleen, stomach, lung meridian; Warming middle-JIAO to relieve pain, promoting flow of QI and blood, main coldness and pain in the epigastrium, food stagnation flatulence, regurgitation vomiting, heatstroke vomiting and diarrhoea, colic of cold type stomachache, arthralgia due to cold-dampnes.Semen setariae, and in, kidney tonifying, heat extraction, removing toxic substances.Control taste deficiency-heat, regurgitation is vomitted, and quenches one's thirst, has loose bowels.Gynura bodinieri Levl., property is bitter, cold syndrome of the stomach, relaxing muscles and tendons to promote blood circulation, removing heat from blood, hemostasis.Cure mainly anemia or severe loss of blood, rheumatalgia, traumatic injury, stomachache, furuncle carbuncle, dermatitis, eczema.Flos Osmanthi Fragrantis fruit, acrid in the mouth, sweet, property is put down, and warming the stomach, suppressing the hyperactive liver, cold expelling, for cold of insufficiency type and stomachache.Asterias amurensis Lutken, salty in the mouth, property is put down; GUIXIN, stomach, large intestine channel; Detoxicating and resolving stagnation of pathogens and stomach and alleviating pain, main stomachache pantothenic acid, diarrhoea.Folium Allii tuberosi, acrid in the mouth, sweet, stomach invigorating, refreshes oneself, and hidroschesis is astringent or styptic treatment for spontaneous sweating.For dysphagia and regurgitation, spontaneous sweating, traumatic injury is controlled in external, swelling and pain due to blood stasis, traumatic hemorrhage.
Beneficial effect of the present invention:
Raw material of Chinese medicine medicine selected by this compound slow-release tablet, Radix Glycyrrhizae Preparata, the Cortex Eucommiae, clear Fructus Solani melongenae, Gynura bodinieri Levl., Asterias amurensis Lutken promoting flow of QI and blood, detoxicating and resolving stagnation of pathogens, have auxiliary hydrogen sulfate chlorine and treat myocardial infarction, Ischemic Stroke or Peripheral arteral disease, acute coronary syndrome than Gray.Radix Glycyrrhizae Preparata, the Radix Aucklandiae, Herba Eupatorii, Flos Osmanthi Fragrantis fruit return spleen, stomach warp, and spleen reinforcing stomach function regulating, appetizing, promoting the circulation of QI to relieve pain are used for strengthening the spleen and nourishing the stomach.Rhizoma Dioscoreae, the Cortex Eucommiae, Semen setariae, Asterias amurensis Lutken, Folium Allii tuberosi returns spleen or/and stomach warp, and warming middle-JIAO to relieve pain, aid digestion and stomach and alleviating pain are used for auxiliary strengthening the spleen and nourishing the stomach.The Cortex Eucommiae, clear Fructus Solani melongenae, Gynura bodinieri Levl. have promoting flow of QI and blood, promote the effect that other drug absorbs.Rhizoma Dioscoreae, Semen setariae, Gynura bodinieri Levl. have the effect of nourishing strong and middle kidney tonifying raising autoimmunity, are conducive to the performance of other medicines effect, promote the recovery of patient body.This compound slow-release tablet each component synergistic action effect is obvious, not only increase the therapeutical effect of hydrogen sulfate chlorine than Gray, and overcome hydrogen sulfate chlorine than Gray to gastrointestinal side effect, there is the effect of strengthening the spleen and nourishing the stomach, reduce the incidence rate of untoward reaction, improve patient compliance.The tumor of pharmaceutic adjuvant and consumption are selected rationally, and formula is simple, and preparation technology is reasonable, stable, and favorable reproducibility, is easy to suitability for industrialized production; Cost is low, is conducive to reducing product price.
Detailed description of the invention
According to following embodiment, the present invention may be better understood.But those skilled in the art will readily understand, concrete material proportion, process conditions and result thereof described by embodiment only should can not limit the present invention described in detail in claims yet for illustration of the present invention.
Embodiment 1
A kind of bisulfate clopidogrel compound slow-release tablet, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 10 parts, Radix Glycyrrhizae Preparata 35 parts, Rhizoma Dioscoreae 50 parts, the Radix Aucklandiae 20 parts, the Cortex Eucommiae 35 parts, Herba Eupatorii 20 parts, clear Fructus Solani melongenae 40 parts, Semen setariae 30 parts, Gynura bodinieri Levl. 30 parts, Flos Osmanthi Fragrantis fruit 45 parts, Asterias amurensis Lutken 15 parts, 20 parts, Folium Allii tuberosi, high viscosity hypromellose 10 parts, low-viscosity hypromellose sodium alginate 5 parts, starch 5 parts, Icing Sugar 5 parts, Polysorbate 2 parts, micropowder silica gel 2 parts.
A preparation method for bisulfate clopidogrel compound slow-release tablet, comprises the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of described compound slow-release tablet and parts by weight, wherein bisulfate clopidogrel pulverized 200 mesh sieves, and high viscosity hypromellose, low-viscosity hypromellose sodium alginate, starch, Icing Sugar, Polysorbate, micropowder silica gel pulverized 100 mesh sieves respectively;
2) extraction of raw material of Chinese medicine medicine, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, by raw material of Chinese medicine medicine Radix Glycyrrhizae Preparata, Rhizoma Dioscoreae, the Radix Aucklandiae, the Cortex Eucommiae, Herba Eupatorii, clear Fructus Solani melongenae, Semen setariae, Gynura bodinieri Levl., Flos Osmanthi Fragrantis fruit, Asterias amurensis Lutken, Folium Allii tuberosi adds in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, filtering residue, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, filtering residue is added in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, merge 2 gained filtrates, vacuum concentration obtains concentrated solution to 1/4th of former filtrate volume,
3) granulate, by bisulfate clopidogrel, step 2) gained concentrated solution, amylum pregelatinisatum, mannitol, sucrose ester, sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, wet granulation; Drying equipment used is fluid bed, and technological parameter is: inlet temperature is 45 ~ 50 DEG C, and temperature of charge is 35 ~ 40 DEG C, and leaving air temp is 30 ~ 35 DEG C;
4) granulate, by step 3) gained granule granulate, cross 30 mesh sieves;
5) tabletting, by step 4) gained granule is by high speed tablet press tabletting, and specification is containing clopidogrel hydrogen sulfate 75mg.
Usage and dosage: oral, every day 1 time, each 1.
Embodiment 2
A kind of bisulfate clopidogrel compound slow-release tablet, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 15 parts, Radix Glycyrrhizae Preparata 38 parts, Rhizoma Dioscoreae 55 parts, the Radix Aucklandiae 23 parts, the Cortex Eucommiae 38 parts, Herba Eupatorii 23 parts, clear Fructus Solani melongenae 42 parts, Semen setariae 32 parts, Gynura bodinieri Levl. 33 parts, Flos Osmanthi Fragrantis fruit 48 parts, Asterias amurensis Lutken 17 parts, 23 parts, Folium Allii tuberosi, high viscosity hypromellose 12 parts, low-viscosity hypromellose sodium alginate 8 parts, starch 7 parts, Icing Sugar 6 parts, Polysorbate 3 parts, micropowder silica gel 3 parts.
A preparation method for bisulfate clopidogrel compound slow-release tablet, comprises the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of described compound slow-release tablet and parts by weight, wherein bisulfate clopidogrel pulverized 200 mesh sieves, and high viscosity hypromellose, low-viscosity hypromellose sodium alginate, starch, Icing Sugar, Polysorbate, micropowder silica gel pulverized 100 mesh sieves respectively;
2) extraction of raw material of Chinese medicine medicine, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, by raw material of Chinese medicine medicine Radix Glycyrrhizae Preparata, Rhizoma Dioscoreae, the Radix Aucklandiae, the Cortex Eucommiae, Herba Eupatorii, clear Fructus Solani melongenae, Semen setariae, Gynura bodinieri Levl., Flos Osmanthi Fragrantis fruit, Asterias amurensis Lutken, Folium Allii tuberosi adds in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, filtering residue, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, filtering residue is added in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, merge 2 gained filtrates, vacuum concentration obtains concentrated solution to 1/4th of former filtrate volume,
3) granulate, by bisulfate clopidogrel, step 2) gained concentrated solution, amylum pregelatinisatum, mannitol, sucrose ester, sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, wet granulation; Drying equipment used is fluid bed, and technological parameter is: inlet temperature is 45 ~ 50 DEG C, and temperature of charge is 35 ~ 40 DEG C, and leaving air temp is 30 ~ 35 DEG C;
4) granulate, by step 3) gained granule granulate, cross 30 mesh sieves;
5) tabletting, by step 4) gained granule is by high speed tablet press tabletting, and specification is containing clopidogrel hydrogen sulfate 75mg.
Usage and dosage: oral, every day 1 time, each 1.
Embodiment 3
A kind of bisulfate clopidogrel compound slow-release tablet, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 20 parts, Radix Glycyrrhizae Preparata 40 parts, Rhizoma Dioscoreae 60 parts, the Radix Aucklandiae 25 parts, the Cortex Eucommiae 40 parts, Herba Eupatorii 25 parts, clear Fructus Solani melongenae 45 parts, Semen setariae 35 parts, Gynura bodinieri Levl. 35 parts, Flos Osmanthi Fragrantis fruit 50 parts, Asterias amurensis Lutken 20 parts, 25 parts, Folium Allii tuberosi, high viscosity hypromellose 15 parts, low-viscosity hypromellose sodium alginate 10 parts, starch 10 parts, Icing Sugar 10 parts, Polysorbate 5 parts, micropowder silica gel 5 parts.
A preparation method for bisulfate clopidogrel compound slow-release tablet, comprises the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of described compound slow-release tablet and parts by weight, wherein bisulfate clopidogrel pulverized 200 mesh sieves, and high viscosity hypromellose, low-viscosity hypromellose sodium alginate, starch, Icing Sugar, Polysorbate, micropowder silica gel pulverized 100 mesh sieves respectively;
2) extraction of raw material of Chinese medicine medicine, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, by raw material of Chinese medicine medicine Radix Glycyrrhizae Preparata, Rhizoma Dioscoreae, the Radix Aucklandiae, the Cortex Eucommiae, Herba Eupatorii, clear Fructus Solani melongenae, Semen setariae, Gynura bodinieri Levl., Flos Osmanthi Fragrantis fruit, Asterias amurensis Lutken, Folium Allii tuberosi adds in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, filtering residue, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, filtering residue is added in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, merge 2 gained filtrates, vacuum concentration obtains concentrated solution to 1/4th of former filtrate volume,
3) granulate, by bisulfate clopidogrel, step 2) gained concentrated solution, amylum pregelatinisatum, mannitol, sucrose ester, sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, wet granulation; Drying equipment used is fluid bed, and technological parameter is: inlet temperature is 45 ~ 50 DEG C, and temperature of charge is 35 ~ 40 DEG C, and leaving air temp is 30 ~ 35 DEG C;
4) granulate, by step 3) gained granule granulate, cross 30 mesh sieves;
5) tabletting, by step 4) gained granule is by high speed tablet press tabletting, and specification is containing clopidogrel hydrogen sulfate 75mg.
Usage and dosage: oral, every day 1 time, each 1.
Embodiment 4
Friability inspection of the present invention
Check according to " Chinese Pharmacopoeia " 2010 editions (two) annex XG tablet friability inspection technique.
Instrument: friability tester.
Method: get some, makes its gross weight be about 6.5g; Blow away the powder come off with hair-dryer, precise weighing, put in cylinder, rotate 100 times.Take out, with method removing powder, precise weighing, less loss weight must not cross 1%, and the sheet that must not detect fracture, be full of cracks and pulverize.This test is general only to be done 1 time.As less loss weight more than 1% time, should recheck 2 times, the average less loss weight of 3 times must not cross 1%, and must not detect fracture, be full of cracks and pulverize sheet.
Result: embodiments of the invention 1-3 gained sample all conforms with the regulations through friability test inspection.
Embodiment 5
Release inspection of the present invention
According to dissolution test method (Chinese Pharmacopoeia version in 2010 two annex XD first methods), take water as solvent, rotating speed is 50 turns per minute, and water temperature 32 ± 0.5 DEG C operates in accordance with the law.Measure the release of sample obtained by embodiment 1-3 respectively.Each sample all sampling in 2,4,8 hours, detects release (%) by HPLC and the results are shown in following table.
Conclusion: result shows that the time of the sustainable slow releasing medicine of compound slow-release tablet of the present invention is 8 hours.Show that this compound slow-release tablet has slow releasing medicine, drug level is steady, and fluctuate little feature.
Embodiment 6
Pharmacodynamic analysis of the present invention
1) clinical data
The present invention is used for the treatment of myocardial infarction patient 274 example and carries out clinical observation treatment, wherein age reckling 37 years old, the maximum 88 years old, 57 years old mean age, the course of disease 1 ~ 5 year.
2) efficacy assessment standard
Be almost recovered: a kind of pain of squeezing property occurs in Symptoms thoracic cavity central authorities, and can delay to neck, chin, arm, back and stomach, other of outbreak symptoms may have dizzy, tachypnea, perspire, shiver, to feel sick and faintness etc. is basic disappears.
Take a turn for the better: a kind of pain of squeezing property occurs in Symptoms thoracic cavity central authorities, and can delay to neck, chin, arm, back and stomach, other of outbreak symptoms may have dizzy, tachypnea, perspire, shiver, feel sick and the partial disappearance such as faintness.
Invalid: symptom is not improved.
3) Therapeutic Method
Compound slow-release tablet prepared by oral embodiments of the invention 3, every day 1 time, each 1.
4) therapeutic effect
A kind of hydrogen sulfate chlorine of the present invention is than Gray compound slow-release tablet through treatment, and 247 examples are fully recovered, and 26 examples take a turn for the better, and 0 example is invalid; Through statistical analysis, cure rate reaches 90.15%, and total effective rate reaches 100.0%, has no untoward reaction over the course for the treatment of, shows drug safety.
Model case:
Case 1: patient Wang, man, 43 years old, patient has dizzy, tachypnea, perspire, shiver, feel sick and the symptom such as faintness obvious, bad through other drug therapeutic effect, use a kind of hydrogen sulfate chlorine of the present invention to treat 3 weeks successfuls than Gray compound slow-release tablet to take a turn for the better, continue use recovery from illness after 2 weeks, in use procedure, have no untoward reaction.
Case 2: patient Deng, man, 66 years old.Patient has dizzy, tachypnea, perspire, shiver, feel sick and the symptom such as faintness obvious, bad through other drug therapeutic effect, use a kind of hydrogen sulfate chlorine of the present invention to treat 5 weeks successfuls than Gray compound slow-release tablet to take a turn for the better, continue use recovery from illness after 3 weeks, in use procedure, have no untoward reaction.
Case 3: patient Zhang, female, 83 years old.Patient has dizzy, tachypnea, perspire, shiver, feel sick and the symptom such as faintness obvious, bad through other drug therapeutic effect, use a kind of hydrogen sulfate chlorine of the present invention to treat 5 weeks successfuls than Gray compound slow-release tablet to take a turn for the better, continue use recovery from illness after 3 weeks, in use procedure, have no untoward reaction.
Above-described embodiment is only be described the preferred embodiment of the present invention; not scope of the present invention is limited; under not departing from the present invention and designing the prerequisite of spirit; the various distortion that those of ordinary skill in the art make technical scheme of the present invention and improvement, all should fall in protection domain that claims of the present invention determines.
Claims (6)
1. a bisulfate clopidogrel compound slow-release tablet, it is characterized in that, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 10 ~ 20 parts, Radix Glycyrrhizae Preparata 35 ~ 40 parts, Rhizoma Dioscoreae 50 ~ 60 parts, the Radix Aucklandiae 20 ~ 25 parts, the Cortex Eucommiae 35 ~ 40 parts, Herba Eupatorii 20 ~ 25 parts, clear Fructus Solani melongenae 40 ~ 45 parts, Semen setariae 30 ~ 35 parts, Gynura bodinieri Levl. 30 ~ 35 parts, Flos Osmanthi Fragrantis fruit 45 ~ 50 parts, Asterias amurensis Lutken 15 ~ 20 parts, 20 ~ 25 parts, Folium Allii tuberosi, high viscosity hypromellose 10 ~ 15 parts, low-viscosity hypromellose sodium alginate 5 ~ 10 parts, starch 5 ~ 10 parts, Icing Sugar 5 ~ 10 parts, Polysorbate 2 ~ 5 parts, micropowder silica gel 2 ~ 5 parts.
2. a kind of bisulfate clopidogrel compound slow-release tablet according to claim 1, it is characterized in that, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 10 parts, Radix Glycyrrhizae Preparata 35 parts, Rhizoma Dioscoreae 50 parts, the Radix Aucklandiae 20 parts, the Cortex Eucommiae 35 parts, Herba Eupatorii 20 parts, clear Fructus Solani melongenae 40 parts, Semen setariae 30 parts, Gynura bodinieri Levl. 30 parts, Flos Osmanthi Fragrantis fruit 45 parts, Asterias amurensis Lutken 15 parts, 20 parts, Folium Allii tuberosi, high viscosity hypromellose 10 parts, low-viscosity hypromellose sodium alginate 5 parts, starch 5 parts, Icing Sugar 5 parts, Polysorbate 2 parts, micropowder silica gel 2 parts.
3. a kind of bisulfate clopidogrel compound slow-release tablet according to claim 1, it is characterized in that, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 15 parts, Radix Glycyrrhizae Preparata 38 parts, Rhizoma Dioscoreae 55 parts, the Radix Aucklandiae 23 parts, the Cortex Eucommiae 38 parts, Herba Eupatorii 23 parts, clear Fructus Solani melongenae 42 parts, Semen setariae 32 parts, Gynura bodinieri Levl. 33 parts, Flos Osmanthi Fragrantis fruit 48 parts, Asterias amurensis Lutken 17 parts, 23 parts, Folium Allii tuberosi, high viscosity hypromellose 12 parts, low-viscosity hypromellose sodium alginate 8 parts, starch 7 parts, Icing Sugar 6 parts, Polysorbate 3 parts, micropowder silica gel 3 parts.
4. a kind of bisulfate clopidogrel compound slow-release tablet according to claim 1, it is characterized in that, component and the parts by weight of this compound slow-release tablet comprise: bisulfate clopidogrel 20 parts, Radix Glycyrrhizae Preparata 40 parts, Rhizoma Dioscoreae 60 parts, the Radix Aucklandiae 25 parts, the Cortex Eucommiae 40 parts, Herba Eupatorii 25 parts, clear Fructus Solani melongenae 45 parts, Semen setariae 35 parts, Gynura bodinieri Levl. 35 parts, Flos Osmanthi Fragrantis fruit 50 parts, Asterias amurensis Lutken 20 parts, 25 parts, Folium Allii tuberosi, high viscosity hypromellose 15 parts, low-viscosity hypromellose sodium alginate 10 parts, starch 10 parts, Icing Sugar 10 parts, Polysorbate 5 parts, micropowder silica gel 5 parts.
5. a preparation method for bisulfate clopidogrel compound slow-release tablet, is characterized in that, comprises the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of compound slow-release tablet described in any one of Claims 1 to 4 and parts by weight, wherein bisulfate clopidogrel pulverized 200 mesh sieves, and high viscosity hypromellose, low-viscosity hypromellose sodium alginate, starch, Icing Sugar, Polysorbate, micropowder silica gel pulverized 100 mesh sieves respectively;
2) extraction of raw material of Chinese medicine medicine, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, by raw material of Chinese medicine medicine Radix Glycyrrhizae Preparata, Rhizoma Dioscoreae, the Radix Aucklandiae, the Cortex Eucommiae, Herba Eupatorii, clear Fructus Solani melongenae, Semen setariae, Gynura bodinieri Levl., Flos Osmanthi Fragrantis fruit, Asterias amurensis Lutken, Folium Allii tuberosi adds in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, filtering residue, be that the water of raw material of Chinese medicine medicine 10 times adds in Chinese medicine extracting tank by parts by weight, open and stir, filtering residue is added in Chinese medicine extracting tank, temperature of charge in Chinese medicine extracting tank is heated to 95 ~ 100 DEG C, constant temperature 30min, 80 orders filter, get filtrate, merge 2 gained filtrates, vacuum concentration obtains concentrated solution to 1/4th of former filtrate volume,
3) granulate, by bisulfate clopidogrel, step 2) gained concentrated solution, amylum pregelatinisatum, mannitol, sucrose ester, sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, wet granulation;
4) granulate, by step 3) gained granule granulate, cross 40 mesh sieves;
5) tabletting, by step 4) gained granule is by high speed tablet press tabletting, and specification is containing clopidogrel hydrogen sulfate 75mg.
6. the preparation method of a kind of bisulfate clopidogrel compound slow-release tablet according to claim 5, it is characterized in that, described granulation step drying equipment used is fluid bed, and technological parameter is: inlet temperature is 45 ~ 50 DEG C, temperature of charge is 35 ~ 40 DEG C, and leaving air temp is 30 ~ 35 DEG C.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114732788A (en) * | 2022-04-14 | 2022-07-12 | 浙江高跖医药科技股份有限公司 | Clopidogrel hydrogen sulfate solid preparation and preparation process thereof |
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| CN1927167A (en) * | 2006-09-29 | 2007-03-14 | 何岩 | Clopidogrel slow, controlled release formulation |
| CN101919890A (en) * | 2010-08-18 | 2010-12-22 | 徐震 | Tablet containing clopidogrel hydrogen sulfate and preparation method thereof |
| KR20130062691A (en) * | 2011-12-05 | 2013-06-13 | 주식회사 테라젠이텍스 | Rapid solid dispersion oral compsition for using wheat bran |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1927167A (en) * | 2006-09-29 | 2007-03-14 | 何岩 | Clopidogrel slow, controlled release formulation |
| CN101919890A (en) * | 2010-08-18 | 2010-12-22 | 徐震 | Tablet containing clopidogrel hydrogen sulfate and preparation method thereof |
| KR20130062691A (en) * | 2011-12-05 | 2013-06-13 | 주식회사 테라젠이텍스 | Rapid solid dispersion oral compsition for using wheat bran |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114732788A (en) * | 2022-04-14 | 2022-07-12 | 浙江高跖医药科技股份有限公司 | Clopidogrel hydrogen sulfate solid preparation and preparation process thereof |
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Application publication date: 20151202 |