CN103285017A - Compound isosorbide mononitrate aspirin sustained-release capsule preparation and preparation method - Google Patents
Compound isosorbide mononitrate aspirin sustained-release capsule preparation and preparation method Download PDFInfo
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- CN103285017A CN103285017A CN2013101927369A CN201310192736A CN103285017A CN 103285017 A CN103285017 A CN 103285017A CN 2013101927369 A CN2013101927369 A CN 2013101927369A CN 201310192736 A CN201310192736 A CN 201310192736A CN 103285017 A CN103285017 A CN 103285017A
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- isosorbide mononitrate
- aspirin
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- enteric
- slow releasing
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- 229960003827 isosorbide mononitrate Drugs 0.000 title claims abstract description 100
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Abstract
The invention discloses a compound isosorbide mononitrate aspirin sustained-release capsule preparation. The compound isosorbide mononitrate aspirin sustained-release capsule preparation is characterized by comprising an isosorbide mononitrate sustained-release capsule preparation and an aspirin enteric-coated preparation, wherein the isosorbide mononitrate sustained-release capsule preparation contains 40-80 parts by weight of isosorbide mononitrate and comprises an immediate-release pellet with 30 percent of isosorbide mononitrate and a sustained-release pellet with 70 percent of isosorbide mononitrate, and the aspirin enteric-coated preparation contains 50-90 parts by weight of aspirin. The invention also provides a preparation method of the compound capsule preparation. With the adoption of the compound isosorbide mononitrate aspirin sustained-release capsule preparation, the curative effects are better improved, the adverse reaction due to stimulation from the aspirin to a gastric mucosa is better reduced, and meanwhile, the isosorbide mononitrate can also satisfy the requirement of stable release in a stomach.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, relate more specifically to a kind of compound recipe isosorbide mononitrate aspirin sustained release capsule preparations and preparation method thereof.
Background technology
Isosorbide mononitrate, chemical name is 1,4:3,6-two dehydration-D-sorbitol-5-Mononitrate is the main bioactive metabolites of Dilatrate-SR, it is one of the most frequently used medicine for the treatment of angina pectoris, myocardial infarction, this medicine particularly increases the venous blood capacity by the expansion peripheral blood vessel, reduces returned blood volume, load before and after reducing heart, thereby reduce myocardial oxygen consumption; Can also promote simultaneously the myocardial blood flow redistribution, improve the ischemic region supply of blood flow, the blood supply of cardiac muscle oxygen supply is tended to balance and bring into play antianginal effect.Because it is rapid-action, effect is strong, determined curative effect, is widely used clinically.Oral conventional tablet absorbs fully at gastrointestinal tract, and bioavailability is nearly 100%, and the serum-concentration peak time is being taken medicine back 30～60 minutes.The 6 hours action time of tablet, on average removing the half-life is 4-5 hour.ISMN forms isosorbide (about 37%) and dextrorotation sorbitol (about 7%) behind the denitration base in serum, by discharging in the urine.The untoward reaction of this medicine mostly is because the vascular dilatation headache that nitrate causes occurring.General consumption is each 20mg, every day 2-3 time.Structural formula is as follows:
Aspirin is actasal, has the effect of antiplatelet aggregation, thromboembolism preventing, thrombolytic in addition.Aspirin makes hematoblastic cyclooxygenase (being prostaglandin synthetase) acetylation, thereby reduce the generation of thromboxane A2 (TXA2), the platelet aggregation that TXA2 is induced produces irreversible inhibitory action, and the II that ADP or epinephrine are induced assembles mutually also resistance inhibitor action; And can suppress platelet aggregation due to low concentration collagen, thrombin, antibody-antigenic compound, some virus and the antibacterial and release reaction and spontaneous gathering the, the formation of pre-preventing thrombosis thus.Oral absorption is rapid, complete, and the protein binding rate of aspirin is low, but the Salicylate protein binding rate after the hydrolysis is 65～90%.Half-life is 15～20 hours; Once take medicine and reached blood medicine peak value in back 1～2 hour.Untoward reaction mostly is and stimulates gastric mucosa and cause gastrointestinal reactions such as nauseating, vomiting, epigastric discomfort or pain.Aspirin is used for the treatment of coronary atherosclerotic heart disease, and its curative effect is confirmed in a large amount of clinical trials of international multicenter.General consumption is each 50-150mg, once a day.Structural formula is as follows:
Clinical trial finds that patient with angina pectoris generally has coronary atherosclerosis and pathological changes in various degree, easily forms thrombosis after the platelet at lesion vessels plaque lesions place is activated, and causes coronary thrombosis.Aspirin has the effect of thromboembolism preventing, thrombolytic, stable and unstable angina pectoris all there is the curative effect that reduces incidence rate of myocardial infarction and sudden death rate, animal experiment, clinical trial prove, aspirin and isosorbide mononitrate share can effectively treat unstable sexual type angina pectoris, and total effective rate reaches more than 90%.And, when isosorbide mononitrate and aspirin share, have synergism and can reduce the generation of side effect.
But domestic and international this compound preparation on the market is double-layer tablet at present, and wherein the isosorbide mononitrate layer is slow release layer, and the aspirin layer is release layer.The initial release of isosorbide mononitrate slow release layer is slower, and blood drug level is on the low side, and drug release is subject to the influence of gastrointestinal motility speed speed, and the release repeatability is relatively poor, and individual variation is bigger; The aspirin layer is release layer, and it often produces as gastrointestinal reactions such as nauseating, vomiting, epigastric discomfort or pain in prophylactic treatment thrombotic disease process, takes the infringement that can cause gastric mucosa for a long time.
Summary of the invention
At above-mentioned deficiency, the invention provides a kind of compound recipe isosorbide mononitrate aspirin sustained release capsule preparations, the present invention simultaneously also provides a kind of preparation method of compound recipe isosorbide mononitrate aspirin sustained release capsule preparations.
A kind of compound recipe isosorbide mononitrate aspirin sustained release capsule preparations, described compound preparation comprises isosorbide mononitrate slow releasing preparation and aspirin enteric-coated preparation, wherein said isosorbide mononitrate slow releasing preparation contains isosorbide mononitrate 40-80 components by weight percent, and described aspirin enteric-coated preparation contains aspirin 50-90 components by weight percent.
Described isosorbide mononitrate slow releasing preparation is micropill, and described aspirin enteric-coated preparation is granule.
Described isosorbide mononitrate slow releasing preparation also comprises the fast release micropill of 30% isosorbide mononitrate dose and the slow-release micro-pill of 70% isosorbide mononitrate dose.
Preferably, described isosorbide mononitrate slow releasing preparation comprises and contains pill core and extended release coatings, film-coat, and the wherein said pill core that contains comprises:
Described aspirin enteric-coated preparation comprises the raw material of following parts by weight:
Aspirin 50-90 weight portion
Enteric-coating material 10-30 weight portion
The material of described diluent comprises one or more in microcrystalline Cellulose, lactose, the starch, preferably microcrystalline cellulose.
The material of described extender comprises one or more in hyprolose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and the carboxymethylstach sodium, preferred hyprolose.
The material of described binding agent comprises a kind of in distilled water, ethanol-water solution, hypromellose, starch slurry, sodium carboxymethyl cellulose or the polyvidone, preferably carboxymethyl cellulose sodium.
The material of described extended release coatings comprises ethyl cellulose and polyvidone, and the weight proportion of described ethyl cellulose and polyvidone is 30: 3-30: 10.
The material of described film-coat comprises a kind of in 3%～8% hypromellose and 1%～3% Pulvis Talci, 5%～15% Opadry stomach dissolution type coating powder, preferred 5%～15% Opadry stomach dissolution type coating powder.
Enteric material in the described enteric-coating material is one or more among Youteqi L100, Youteqi L100-55 and the polyacrylic acid resin II.Described enteric-coating material also comprises plasticizer and antiplastering aid, and described plasticizer comprises one or more in triethyl citrate, tributyl citrate, diethyl phthalate, the propylene glycol.Described antiplastering aid comprises one or more in Pulvis Talci, magnesium stearate, silicon dioxide, glyceryl monostearate, the Glyceryl Behenate.
Preferably, described enteric-coating material comprises Youteqi L100, triethyl citrate and Pulvis Talci.
Preferably, described compound recipe isosorbide mononitrate aspirin sustained release capsule preparations makes by the following method:
The preparation of step 1, isosorbide mononitrate slow releasing preparation:
1.1, the preparation of 1% sodium carboxymethyl cellulose, 10% alcoholic solution: the sodium carboxymethyl cellulose that takes by weighing recipe quantity is put in 10% the ethanol of recipe quantity and is uniformly dispersed, and adds the water of recipe quantity again, stirring and dissolving, namely.
1.2, the isosorbide mononitrate, microcrystalline Cellulose and the hyprolose mixing diluents that take by weighing recipe quantity be even, add 1% sodium carboxymethyl cellulose, 10% alcoholic solution soft material processed, employing is extruded spheronizator and prepared the ball core, and is dry in the fluid bed, screening gets isosorbide mononitrate ball core.
1.3, the preparation of extended release coatings coating solution: take by weighing in the ethyl cellulose N100 of recipe quantity and the ethanol that polyvidone is put recipe quantity, stirring and dissolving, namely.
1.4, the preparation of film-coat coating solution: the Opadry stomach dissolution type coating powder that takes by weighing recipe quantity is put in the water of recipe quantity, stirs, namely.
1.5, the ball core after will sieving takes out 70% and puts and wrap extended release coatings in the fluid bed, gets the isosorbide mononitrate slow-release micro-pill; 30% ball core is put and is wrapped film-coat in the fluid bed, gets the isosorbide mononitrate fast release micropill.Mix, get the isosorbide mononitrate slow releasing preparation.
The preparation of step 2, aspirin enteric-coated granule:
2.1, the Youteqi L100 that takes by weighing recipe quantity puts in the ethanol of recipe quantity, stirring and dissolving adds triethyl citrate and the Pulvis Talci of recipe quantity again, stirs, and gets enteric coating liquid.
2.2, the aspirin that takes by weighing recipe quantity puts coating in the fluid bed, gets aspirin enteric-coated granule.
Isosorbide mononitrate is prepared into micropill take after, extensively be evenly distributed in the gastrointestinal tract.Since dosage incline decentralized, medicine increases at the distribution area on gastrointestinal surface, and the transhipment unable to take food thing in gastrointestinal tract is carried the influence of the rhythm and pace of moving things, and namely the sphincter of pylorus closed type still can be passed through pylorus, absorb the influence that generally is not subjected to gastric emptying at gastrointestinal, drug bioavailability is improved; Its drug release behavior is the summation of forming each piller drug release behavior of a dosage simultaneously, and the defective of indivedual pillers in preparation can not produce whole drug release behavior and have a strong impact on, and is better than the preparation of being made up of a unit.
Aspirin is prepared into the stimulation that can reduce behind the enteric coated particles gastric mucosa, reduces the generation of side reaction.Considering that the treatment of coronary heart disease need take medicine for a long time, is enteric coatel tablets with the aspirin of drug combination treatment coronary heart disease therefore, to reduce untoward reaction clinically.And the aspirin in the existing isosorbide mononitrate aspirin compound preparation partly is quick releasing formulation, prolonged application is big to gastrointestinal stimulation, and can not reach the effect same with single medicine coupling, and just can reach the effect same with single medicine coupling by our method, and can overcome the untoward reaction of aspirin.Plurality of advantages such as simultaneously aspirin is made enteric coated particles, and it is constant to have produced the medicine gastric emptying time that the multiparticulates drug delivery system has again, and onset time is short obviously are better than the effect that single medicine coupling produces again.
Description of drawings
Fig. 1 is aspirin release profiles in 0.1mol/L hydrochloric acid in the compound recipe isosorbide mononitrate aspirin sustained release capsule preparations of the present invention.
Fig. 2 is aspirin release profiles in phosphate buffer in the compound recipe isosorbide mononitrate aspirin sustained release capsule preparations of the present invention.
Fig. 3 is aspirin release profiles in 0.1mol/L hydrochloric acid in the compound recipe isosorbide mononitrate sustained release tablets.
Fig. 4 is curve during in vivo medicine of isosorbide mononitrate in the compound recipe isosorbide mononitrate sustained release tablets.
Fig. 5 is curve during in vivo medicine of isosorbide mononitrate slow-release micro-pill in the compound recipe isosorbide mononitrate aspirin sustained release capsule preparations of the present invention.
The specific embodiment:
Below the present invention is described in further detail, can implement according to this with reference to the description literal to make those skilled in the art.
The present invention will be further described below in conjunction with embodiment, but be not limited to following examples.Embodiment 1, and compound recipe isosorbide mononitrate aspirin sustained release capsule preparations is produced 1000 capsules
Ball core prescription:
The extended release coatings prescription:
Ethyl cellulose N100 30g
30 POVIDONE K 30 BP/USP 30 3g
Ethanol 1000ml
The film-coat prescription:
Opadry stomach dissolution type coating powder 12g
Water 88g
Aspirin enteric-coated granule prescription:
Aspirin 75g
The enteric coating prescription:
Ball core prescription:
The extended release coatings prescription:
Ethyl cellulose N100 30g
30 POVIDONE K 30 BP/USP 30 5g
Ethanol 1000ml
The film-coat prescription:
Opadry stomach dissolution type coating powder 12g
Water 88g
Aspirin enteric-coated granule prescription:
Aspirin 75g
The enteric coating prescription:
Ball core prescription:
The extended release coatings prescription:
Ethyl cellulose N100 30g
30 POVIDONE K 30 BP/USP 30 6g
Ethanol 1000ml
The film-coat prescription:
Opadry stomach dissolution type coating powder 12g
Water 88g
Aspirin enteric-coated granule prescription:
Aspirin 75g
The enteric coating prescription:
Above embodiment 1, embodiment 2, embodiment 3 described compound recipe isosorbide mononitrate capsule preparations make by the following method:
The preparation of step 1, isosorbide mononitrate slow releasing preparation:
1.1, the preparation of 1% sodium carboxymethyl cellulose, 10% alcoholic solution: the sodium carboxymethyl cellulose that takes by weighing recipe quantity is put in 10% the ethanol of recipe quantity and is uniformly dispersed, and adds the water of recipe quantity again, stirring and dissolving, namely.
1.2, the isosorbide mononitrate, microcrystalline Cellulose and the hyprolose mixing diluents that take by weighing recipe quantity be even, add 1% sodium carboxymethyl cellulose, 10% alcoholic solution soft material processed, employing is extruded spheronizator and prepared the ball core, and is dry in the fluid bed, screening gets isosorbide mononitrate ball core.
1.3, the preparation of extended release coatings coating solution: take by weighing in the ethyl cellulose N100 of recipe quantity and the ethanol that polyvidone is put recipe quantity, stirring and dissolving, namely.
1.4, the preparation of film-coat coating solution: the Opadry stomach dissolution type coating powder that takes by weighing recipe quantity is put in the water of recipe quantity, stirs, namely.
1.5, the ball core after will sieving takes out 70% and puts and wrap extended release coatings in the fluid bed, gets the isosorbide mononitrate slow-release micro-pill; 30% ball core is put and is wrapped film-coat in the fluid bed, gets the isosorbide mononitrate fast release micropill.Mix, get the isosorbide mononitrate slow releasing preparation.
The preparation of step 2, aspirin enteric-coated granule:
2.1, the Youteqi L100 that takes by weighing recipe quantity puts in the ethanol of recipe quantity, stirring and dissolving adds triethyl citrate and the Pulvis Talci of recipe quantity again, stirs, and gets enteric coating liquid.
2.2, the aspirin that takes by weighing recipe quantity puts coating in the fluid bed, gets aspirin enteric-coated granule.
The release situation of the compound recipe isosorbide mononitrate aspirin capsule preparations that the present invention prepares is described below by chart, and compare with the release situation of on the market known formulations compound recipe isosorbide mononitrate sheet, further specify advantage of the present invention, specifically see Fig. 1 to Fig. 5.
In Fig. 1, the release profiles of aspirin in 0.1mol/L hydrochloric acid in the prepared compound recipe isosorbide mononitrate aspirin sustained release capsule preparations of embodiment 1, embodiment 2 and embodiment 3, as can be seen from Figure, aspirin does not discharge in 0.1mol/L hydrochloric acid substantially, can satisfy the requirement that aspirin enteric-coated location discharges, discharge in 0.1mol/L hydrochloric acid with aspirin in Fig. 3 compound recipe isosorbide mononitrate sustained release tablets and to compare, can obviously reduce medicine to the damage of gastric mucosa, improve patient's compliance.
In Fig. 2, article three, curve is respectively the release profiles of aspirin in phosphate buffer in the prepared compound recipe isosorbide mononitrate aspirin sustained release capsule preparations of embodiment 1, embodiment 2, embodiment 3, aspirin can reach release fully in the preparation of the present invention in simulated intestinal fluid as can be seen, the release behavior basically identical of the Baysprin that its release behavior and Bayer pharmaceuticals produce, so can not influence the medicine absorption in vivo, advantages such as it is constant that it has the medicine gastric emptying time simultaneously, and individual variation is little.
In Fig. 4, curve when curve is in vivo medicine of isosorbide mononitrate slow-release micro-pill in the compound recipe isosorbide mononitrate aspirin sustained release capsule preparations of the present invention during medicine, the curve contrast as can be seen during with in vivo medicine of isosorbide mononitrate in the compound recipe isosorbide mononitrate sustained release tablets among Fig. 5, the initial blood drug level height of isosorbide mononitrate in the preparation of the present invention, rapid-action, mainly be owing to contain 30% isosorbide mononitrate immediate release section in the preparation of the present invention, simultaneously as can be seen in the preparation of the present invention isosorbide mononitrate release individual variation in vivo little, it is good to discharge homogeneity.
The present invention is not limited to specific embodiment described above, and those skilled in the art can change a plurality of details of the present invention in the restricted portion in claim of the present invention.
Claims (9)
1. compound recipe isosorbide mononitrate aspirin sustained release capsule preparations, it is characterized in that, described compound preparation comprises isosorbide mononitrate slow releasing preparation and aspirin enteric-coated preparation, wherein said isosorbide mononitrate slow releasing preparation contains isosorbide mononitrate 40-80 components by weight percent, and described aspirin enteric-coated preparation contains aspirin 50-90 components by weight percent.
2. compound recipe isosorbide mononitrate aspirin sustained release capsule preparations as claimed in claim 1 is characterized in that described isosorbide mononitrate slow releasing preparation is micropill, and described aspirin enteric-coated preparation is granule.
3. compound recipe isosorbide mononitrate aspirin sustained release capsule preparations as claimed in claim 2, it is characterized in that described isosorbide mononitrate slow releasing preparation comprises the fast release micropill of 30% isosorbide mononitrate dose and the slow-release micro-pill of 70% isosorbide mononitrate dose.
4. as claim 2,3 described compound recipe isosorbide mononitrate aspirin sustained release capsule preparations, it is characterized in that described isosorbide mononitrate slow releasing preparation mainly comprises and contains pill core, extended release coatings, film-coat, the wherein said pill core that contains comprises:
5. as claim 2,3 described compound recipe isosorbide mononitrate aspirin sustained release capsule preparations, it is characterized in that described aspirin enteric-coated preparation comprises the raw material of following parts by weight:
Aspirin 50-90 weight portion
Enteric-coating material 10-30 weight portion.
6. compound recipe isosorbide mononitrate aspirin sustained release capsule preparations as claimed in claim 4 is characterized in that,
Described diluent is selected from one or both and two or more combinations, the wherein preferably microcrystalline cellulose in microcrystalline Cellulose, lactose, the starch;
Described extender is selected from one or more the mixture in hyprolose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and the carboxymethylstach sodium, wherein preferred hyprolose;
Described binding agent is selected from distilled water, ethanol-water solution, hypromellose, starch slurry, sodium carboxymethyl cellulose or polyvidone, wherein preferably carboxymethyl cellulose sodium;
Described extended release coatings adopts ethyl cellulose and polyvidone as filmogen, and the weight ratio of ethyl cellulose and polyvidone is 30: 3～30: 10;
Described film-coat adopts 3%～8% hypromellose and 1%～3% Pulvis Talci or 5%～15% Opadry stomach dissolution type coating powder as filmogen, wherein preferred 5%～15% Opadry stomach dissolution type coating powder.
7. compound recipe isosorbide mononitrate aspirin sustained release capsule preparations as claimed in claim 5 is characterized in that,
Described enteric-coating material is one or more among Youteqi L100, Youteqi L100-55 and the polyacrylic acid resin II, wherein preferred Youteqi L100;
Described enteric-coating material also comprises plasticizer and antiplastering aid, and described plasticizer comprises one or more in triethyl citrate, tributyl citrate, diethyl phthalate, the propylene glycol, wherein the optimization citric acid triethyl;
Described antiplastering aid comprises one or more in Pulvis Talci, magnesium stearate, silicon dioxide, glyceryl monostearate, the Glyceryl Behenate, wherein the preferably talc powder.
8. as claim 6,7 arbitrary described compound recipe isosorbide mononitrate aspirin sustained release capsule preparations, it is characterized in that described compound recipe isosorbide mononitrate aspirin sustained release capsule preparations makes by following preparation method:
The preparation of step 1, isosorbide mononitrate slow releasing preparation:
1.1, the isosorbide mononitrate, diluent and the extender that take by weighing recipe quantity mix, and adds binding agent soft material processed, adopts to extrude spheronizator and prepare the ball core, and be dry in the fluid bed, sieves, and gets isosorbide mononitrate ball core;
1.2, one or more filmogens add ethanol and make the extended release coatings coating solution, one or more filmogens add water and make the film-coat coating solution;
1.3, the ball core after will sieving takes out 70% and puts and wrap extended release coatings in the fluid bed, gets the isosorbide mononitrate slow-release micro-pill; 30% ball core is put and is wrapped film-coat in the fluid bed, gets the isosorbide mononitrate fast release micropill; Mix, get the isosorbide mononitrate slow releasing preparation;
The preparation of step 2, aspirin enteric-coated granule:
2.1, in ethanol, add the recipe quantity enteric-coating material, get enteric coating liquid;
2.2, the aspirin of recipe quantity puts coating in the fluid bed, gets aspirin enteric-coated granule;
Step 3, with above-mentioned isosorbide mononitrate slow releasing preparation and aspirin enteric-coated granule, according to recipe quantity mixing filling capsule, namely.
9. preparation method for preparing as claim 6,7 arbitrary described compound recipe isosorbide mononitrate aspirin sustained release capsule preparations is characterized in that described preparation method is taked the following step:
The preparation of step 1, isosorbide mononitrate slow releasing preparation:
1.1, the isosorbide mononitrate, diluent and the extender that take by weighing recipe quantity mix, it is soft to add binding agent system, adopts to extrude spheronizator and prepare the ball core, dry in the fluid bed, screening gets isosorbide mononitrate ball core;
1.2, one or more filmogens add ethanol and make the extended release coatings coating solution, one or more filmogens add water and make the film-coat coating solution;
1.3, the ball core after will sieving takes out 70% and puts and wrap extended release coatings in the fluid bed, gets the isosorbide mononitrate slow-release micro-pill; 30% ball core is put and is wrapped film-coat in the fluid bed, gets the isosorbide mononitrate fast release micropill; Mix, get the isosorbide mononitrate slow releasing preparation;
The preparation of step 2, aspirin enteric-coated granule:
2.1, the recipe quantity enteric-coating material adds ethanol and makes enteric coating liquid;
2.2, the aspirin of recipe quantity puts coating in the fluid bed, gets aspirin enteric-coated granule;
Step 3, with above-mentioned isosorbide mononitrate slow releasing preparation and aspirin enteric-coated granule, according to recipe quantity mixing filling capsule, namely.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105106225A (en) * | 2015-09-10 | 2015-12-02 | 石家庄市智同医药科技有限公司 | Compound dipyridamole and aspirin tablet and preparation method thereof |
| CN105902509A (en) * | 2015-09-28 | 2016-08-31 | 天方药业有限公司 | Compound isosorbide mononitrate sustained release tablet and preparation method thereof |
| CN106138012A (en) * | 2016-08-01 | 2016-11-23 | 广东隆信制药有限公司 | A kind of preparation method of isosorbide mononitrate slow releasing capsule |
| CN106581088A (en) * | 2016-12-07 | 2017-04-26 | 郑州郑先医药科技有限公司 | Drug for treating coronary heart diseases |
| CN109316467A (en) * | 2018-01-31 | 2019-02-12 | 合肥合源药业有限公司 | Isosorbide Mononitrate spansule and preparation method thereof |
| CN113599387A (en) * | 2021-09-15 | 2021-11-05 | 山东中医药大学附属医院 | Compound preparation and application thereof in preparing medicament for treating angina |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105106225A (en) * | 2015-09-10 | 2015-12-02 | 石家庄市智同医药科技有限公司 | Compound dipyridamole and aspirin tablet and preparation method thereof |
| CN105902509A (en) * | 2015-09-28 | 2016-08-31 | 天方药业有限公司 | Compound isosorbide mononitrate sustained release tablet and preparation method thereof |
| CN105902509B (en) * | 2015-09-28 | 2018-08-17 | 天方药业有限公司 | A kind of compound isosorbide mononitrate sustained release tablets and preparation method thereof |
| CN106138012A (en) * | 2016-08-01 | 2016-11-23 | 广东隆信制药有限公司 | A kind of preparation method of isosorbide mononitrate slow releasing capsule |
| CN106138012B (en) * | 2016-08-01 | 2019-03-15 | 广东隆信制药有限公司 | A kind of preparation method of Isosorbide Mononitrate spansule |
| CN106581088A (en) * | 2016-12-07 | 2017-04-26 | 郑州郑先医药科技有限公司 | Drug for treating coronary heart diseases |
| CN109316467A (en) * | 2018-01-31 | 2019-02-12 | 合肥合源药业有限公司 | Isosorbide Mononitrate spansule and preparation method thereof |
| CN113599387A (en) * | 2021-09-15 | 2021-11-05 | 山东中医药大学附属医院 | Compound preparation and application thereof in preparing medicament for treating angina |
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Effective date of registration: 20210901 Address after: 135000 Room 101, building a, 66 Xinglong Street, Meihekou City, Tonghua City, Jilin Province Patentee after: Jilin Tianheng Pharmaceutical Co., Ltd Address before: Room 2211, f Hotel, yard 18, Shijingshan Road, Shijingshan District, Beijing 100076 Patentee before: Liu Guangquan Patentee before: Wu Yan Patentee before: Zhang Fucheng |