CN101185624A - Novel composing prescription sustained-release preparation for treating high blood pressure and preparation method thereof - Google Patents
Novel composing prescription sustained-release preparation for treating high blood pressure and preparation method thereof Download PDFInfo
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- CN101185624A CN101185624A CNA2007101784961A CN200710178496A CN101185624A CN 101185624 A CN101185624 A CN 101185624A CN A2007101784961 A CNA2007101784961 A CN A2007101784961A CN 200710178496 A CN200710178496 A CN 200710178496A CN 101185624 A CN101185624 A CN 101185624A
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Abstract
The invention relates to a sustained release preparation of a novel prescription for treating hypertension and the preparing method thereof. The novel prescription comprises a heart selective Beta1 receptor blocker metoprolol and an angiotensin II receptor antagonist (sartan drugs). The sustained release preparation consists of delayed release part and rapid release part, wherein the heart selective Beta1 receptor blocker metoprolol is the delayed release part, with first hour releasing 25-45%, fourth hour releasing 40-75% and eighth hour releasing over 75%; the angiotensin II receptor antagonist (sartan drugs) is the rapid release part, with 45 minutes dissolution over 75%. The composition has both rapid and prolonged action. The invention discloses in vitro drug release characteristics and preparation method thereof.
Description
Technical field
The present invention relates to a kind of slow releasing preparation that is used for the treatment of hypertensive novel composing prescription and preparation method thereof, belong to medical technical field.
Background technology
Metoprolol belongs to the selectivity β1Shou Tizuzhiji, myocardium β1Shou Ti capable of blocking, and decreased heart rate suppresses the conduction of cardiac contractile force and chamber, and cardiac output and blood flow are reduced, and myocardial oxygen consumption reduces; Also can reduce the secretion of feritin and aldosterone, make antiotasis descend hypovolemia and blood pressure drops.Can be used for treating hypertension and angina pectoris, reduce the incidence rate of myocardial infarction, the mortality rate after the reduction myocardial infarction.There is one to studies confirm that metoprolol sustained-release sheet treatment hypertension curative effect.Method: 38 examples are breathed out the Chinese two family's patients with hypertension and are taken 4 weeks of metoprolol sustained-release sheet, and wherein 23 examples continued to take 12 weeks.The result: total effective rate is 84.2%, and to breathe out family's hypertension curative effect 86.3%, Han nationality's hypertension is 81.2%.Conclusion: the metoprolol sustained-release sheet all has obvious hypotensive effect to breathing out the Chinese two families, and can keep the 24h drug effect, and oral easy, and side effect is little.Put so metoprolol is an a kind of treatment peace umbrella, can take for a long time, a kind of more satisfactory depressor.
Angiotensin ii receptor antagonist is the important drugs that the new class that hypertension, arteriosclerosis, myocardial hypertrophy, heart failure, diabetic nephropathy etc. are had a good action after angiotensin converting enzyme inhibitor (ACEI) acts on renin-angiotensin system (RAS).It acts on the terminal acceptor levels of RAS, and is more abundant, more direct, have more and optionally block ARS, and does not have side effect such as dry cough, vasodilation.Along with continuing to bring out of ATIIRa class medicine, clinical practice is extensive day by day, is classified as one of six big class antihypertensive drug by World Health Organization (WHO) and international hypertension alliance.Angiotensin ii receptor antagonist commonly used has losartan, valsartan, irbesartan, Candesartan, telmisartan, Ai Pushatan, Eprosartan, irbesartan, Olmesartan.
Metoprolol and angiotensin ii receptor antagonist all can be used for the treatment of hypertension, they come indirectly or directly to play the effect of blood pressure lowering respectively with different action sites and mode, the doctor can select suitable angiotensin ii receptor antagonist and metoprolol use in conjunction as required clinically, to play collaborative mutually effect, but often because dosage is grasped inaccurate, can bring discomfort to the patient, perhaps not reach ideal antihypertensive effect.Use if two kinds of medicines are made compound preparation, will improve the hypotensive effect of metoprolol and angiotensin ii receptor antagonist greatly according to the proportioning of science.
Summary of the invention
Technology described in the invention relates to field of medicaments, specifically is meant a kind of slow releasing preparation that contains heart selectivity β1Shou Tizuzhiji metoprolol and a kind of angiotensin ii receptor antagonist.Said preparation quick-acting long-acting having both, obviously reduces patient and takes number of times, the convenient use through the science design.
Described heart selectivity β1Shou Tizuzhiji metoprolol can be that metoprolol is the salt of the various acid groups of active component, example hydrochloric acid salt, tartrate, succinate etc.; Described active component metoprolol can be left-handed optical isomer, left-handed optical isomer and raceme.
Described angiotensin ii receptor antagonist includes but are not limited to irbesartan, Olmesartan, Candesartan, telmisartan, valsartan, Eprosartan, losartan isoreactivity composition, and they can exist with the form of esters or salt
The hypertensive novel composing prescription of described treatment includes but are not limited to following combination: metoprolol+irbesartan, metoprolol+Olmesartan, metoprolol+candesartan Cilexetil, metoprolol+telmisartan, metoprolol+valsartan, metoprolol+Eprosartan, metoprolol+Losartan Potassium.
In the described novel composing prescription, the unit dose of metoprolol is 100mg (in an active component); The unit dose of irbesartan is 0.075g~0.6g, is preferably 0.15g~0.30g; The unit dose of olmesartan medoxomil is 10mg~80mg, is preferably 20mg~40mg; The unit dose of candesartan Cilexetil is 1~24mg, is preferably 4~12mg; The unit dose of telmisartan is 10~80mg, is preferably 20~40mg; The unit dose of valsartan is 20~240mg, is preferably 80~160mg; The unit dose of Eprosartan is 200~800mg, is preferably 600mg; The unit dose of Losartan Potassium is 25~100mg, is preferably 50mg
This slow releasing preparation is made up of slow-released part and immediate release section.Wherein heart selectivity β1Shou Tizuzhiji metoprolol is a slow-released part, and angiotensin ii receptor antagonist is an immediate release section.Wherein:
The metoprolol sustained-release part, in the dissolution in vitro test, metoprolol stripping in the 1st hour discharges the 25~45%, 4th hour and discharges release in the 45~75%, 8th hour more than 75%.
The angiotensin ii receptor antagonist immediate release section, in the environment of simulation simulated gastric fluid, medicine 45 minutes was leachable greater than 75% at body.
Sustained-release matrix of the present invention, comprise hydroxypropyl methylcellulose HPMC-4M, HPMC-15M, HPMC-100M, one of polyvinylpyrrolidone, ethyl cellulose, hydroxyethyl-cellulose, hexadecanol, octadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, sodium carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, chitin or they optional two or more.
In the sustained release coating of the present invention prescription, slow-release material commonly used comprises ethyl cellulose and aqueous dispersion thereof, stearic acid, cellulose acetate, crylic acid resin (as RS100, RL100, RS30D, RL30D, NE30D) one of them or several mixture.In the sustained release coating prescription, can also add some porogen, antiplastering aid, plasticizer etc. in case of necessity.
Slow releasing preparation described above is taken once every day, is used for the treatment of various types of hypertension symptoms.
Below test further illustrates clinical efficacy of the present invention
Test 1: metoprolol+valsartan composition
Purpose: the treatment of paired observation metoprolol+valsartan composition and valsartan is light, moderate essential hypertension patient's clinical efficacy and security method menu: adopt at random, open, parallel, single blind contrast method.Be divided into two groups at random, treatment group (n=68): metoprolol+valsartan composition, oral, 180mg/ time, 2/ day, matched group (n=66): valsartan, oral, 80mg/ time, 2/ day.Effective percentage and the rate of side effects after 6 weeks, 8 weeks and 12 weeks treated in observation. and the result treats the 2nd week beginning systolic pressure (SBP), diastolic pressure (DBP) than all obviously reducing (P<0.01) before treating for two groups; Blood pressure continues steadily to descend during whole treatment, and the 8 all metoprolols+valsartan composition group antihypertensive effect of taking medicine is better than the valsartan group, total effective rate metoprolol+valsartan composition group be 79.1% and the valsartan group be 63.6%; Total effective rate is 89.5% and 74.8% after 12 weeks of treatment; Ambulatory blood pressure monitoring (ABPM) shows that the paddy p-ratio of metoprolol+valsartan composition rises sharply similar to valsartan (P>0.05) with reduction blood pressure in early morning. and two groups of side reactions are all very slight. and conclusion metoprolol+valsartan composition and valsartan all are effective, safe long-acting depressor, and metoprolol+valsartan composition each side performance all is better than valsartan.
Test 2. metoprolols+losartan compositions
Hypotensive activity, untoward reaction that purpose is observed metoprolol+losartan compositions and losartan reach metabolic influence.Method: choose essential hypertension example 129 examples by WHO standard in 1999, after 2 all flush period, be divided into metoprolol+losartan compositions group (66 examples at random, oral, 150mg/ time, 2/ day) and the losartan group (63 examples, oral, 50mg/ time, 2/ day), 8 weeks of the course of treatment, duration of test, dietary structure, living habit and non-drug therapy measure remain unchanged, and forbidding may influence the medicine of blood pressure.Survey the seat blood pressure by fixing doctor, before the blood pressure lowering treatment and 8 week of treatment back survey fasting glucose, blood fat, blood potassium and urinary albumin excretion.The therapeutic evaluation produce effects: diastolic pressure (DBP) decline 〉=10mmHg and reduce to normal (<90mmHg) or more than the decline 20mmHg.Effectively: DBP decline<10mmHg but reduce to normal or 10~the 19mmHg that descends.Invalid: as not reach above-mentioned standard.Total effective rate=obvious effective rate+put rate.The result: metoprolol+losartan compositions and losartan group are being taken medicine the back during 4 weeks, and A organizes total effective rate 73.6%, obvious effective rate 54.5%; B organizes total effective rate 63.5%, obvious effective rate 42.4%.When taking medicine for 8 weeks, A organizes total effective rate 82.7%, and wherein obvious effective rate 73.6%; B organizes total effective rate 71.0%, obvious effective rate 60.1%.Comparing difference has significance (P<0.05) between two groups.The untoward reaction A of medicine organizes dizzy 3 examples, weak or feeling of fatigue 4 examples, and xerostomia 2 examples, incidence rate are 13.6% (9/66).B organizes dizzy 3 examples, weak or feeling of fatigue 5 examples, and xerostomia 2 examples, poor appetite 1 example, incidence rate are 17.5% (11/63).Comparing difference does not have significance between two groups.Conclusion: metoprolol+losartan compositions and losartan all have high efficiency hypotensive effect to the hyperpietic, and untoward reaction is few, and metoprolol+losartan compositions is more more remarkable than the hypotensive effect of losartan.
Test 3 metoprolols+irbesartan compositions
Purpose: it is light to observe the treatment of metoprolol+irbesartan compositions and metoprolol sheet, the curative effect of moderate essential hypertension and untoward reaction. method: adopt double blinding, dual analog, perspective parallel test design, treatment group (n=28): metoprolol+irbesartan compositions, oral, 250mg/ time, 2/ day, contrast medicine (n=24): oral, 100mg/ time, 2/ day. 8 week treatment course of treatment before and after look: hematuria routine, hepatic and renal function, blood electrolyte and blood fat, electrocardiogram. relatively there were significant differences between the blood pressure group after two groups of medications of result, the total effective rate of two medicine blood pressure lowerings is respectively 86.3% and 70.6%, heart rate does not all have obviously and slows down after two groups of medications, the no abnormal change of lab testing. untoward reaction situation: metoprolol+irbesartan compositions group cardiopalmus 1 example, the sense of taste changes 1 example, total incidence rate 7.1%. metoprolol sheet group 3 examples of coughing, itching throat, dizzy each 1 example, total incidence rate is the 16.6%. conclusion: metoprolol+irbesartan combination treatment is light, moderate hypertension and metoprolol sheet are relatively, blood pressure lowering effect is better, toleration is better, side effect is less, to the heart, liver, kidney and hemopoietic system do not have the overt toxicity effect.
The specific embodiment
Come compound ambroxol hydrochloride decarboxylation loratadine slow releasing preparation of the present invention and preparation method thereof done further specifying by following example, but be not limited in following example.
Embodiment 1 compound recipe spectinomycin hydrochloride Eprosartan double-layer sustained release tablets
Prescription:
Component | Content |
Spectinomycin hydrochloride Eprosartan HPMC-15M EC lactose 80% alcoholic solution microcrystalline Cellulose purified water Pulvis Talci is made altogether | An amount of 1000 of an amount of 200g of 100g 600g 80g 20g 30g |
Preparation method:
Spectinomycin hydrochloride is crossed 100 mesh sieves, and HPMC-15M, EC, lactose are crossed 60 mesh sieves, and with 80% alcoholic solution system soft material, 16 mesh sieves are granulated behind the supplementary material mix homogeneously, 40 ℃ of dryings, and 16 mesh sieve granulate add the Pulvis Talci mix homogeneously, and are standby; With Eprosartan and microcrystalline Cellulose mix homogeneously,, be prepared into the immediate-release granules of big or small basically identical with method in addition with purified water system soft material.Successively take by weighing above two kinds of granules in proportion, make double-layer sustained release tablets.
Embodiment 2 compound recipe spectinomycin hydrochloride irbesartan double-layer sustained release tablets
Prescription:
Component | Content |
Spectinomycin hydrochloride irbesartan HPMC-15M HPMC-100M sucrose 80% alcoholic solution lactose monohydrate purified water | An amount of 80g of 100g 150g 60g 15g 30g is an amount of |
Micropowder silica gel is made altogether | An amount of 1000 |
Preparation method:
Spectinomycin hydrochloride is crossed 100 mesh sieves, and HPMC-15M, HPMC-100M, sucrose are crossed 60 mesh sieves, and with 80% alcoholic solution system soft material, 16 mesh sieves are granulated behind the supplementary material mix homogeneously, 40 ℃ of dryings, and 16 mesh sieve granulate add part micropowder silica gel mix homogeneously, and are standby; With irbesartan and lactose monohydrate mix homogeneously,, be prepared into the immediate-release granules of big or small basically identical with method in addition with purified water system soft material.Successively take by weighing above two kinds of granules in proportion, make double-layer sustained release tablets.
Embodiment 3 compound recipe spectinomycin hydrochloride candesartan Cilexetil film-coat slow releasing tablet
Spectinomycin hydrochloride label prescription:
Component | Content |
Spectinomycin hydrochloride micro crystal cellulose milk sugar purified water is made altogether | An amount of 1000 of 100g 250g 75g |
The coating prescription that contains candesartan Cilexetil:
Component | Content |
Candesartan Cilexetil ethyl cellulose acrylic resin RS100 tween~80 Pulvis Talci ethanol solutions | 4g 12g 15g 2g 4g 400ml |
Preparation method:
Tartaric acid Mei Tuoluo is crossed 100 mesh sieves, and microcrystalline Cellulose, lactose are crossed 60 mesh sieves, and water is made soft material in right amount behind the supplementary material mix homogeneously, and 20 mesh sieves are granulated, drying, and 18 mesh sieve granulate, tabletting, standby; Ethyl cellulose, acrylic resin RS100 are placed ethanol solution, and fully stirring makes it to dissolve fully, adds candesartan Cilexetil, Pulvis Talci, tween~80 continuation stirrings, obtains uniform suspension, and is standby; Open the coating pelletizing machine, regulate 30 ℃ of wind pressure 0.5bar, temperature, adjust rotary speed 150~200rpm, start peristaltic pump, spray into pastille suspendible coating solution, after coating finished, discharging got final product.
Embodiment 4 compound recipe metroprolol succinate Olmesartan sustained-release micro-pill capsules
Prescription:
Component | Content |
Metroprolol succinate Olmesartan octadecanol PVP microcrystalline Cellulose 0.5%HPMC purifying aqueous solutions water is made altogether | An amount of 1000 of 100g 20g 50g 10g 120g |
Preparation method:
Metroprolol succinate is crossed 100 mesh sieves, join stir in the fused octadecanol after, continue to add PVP as the porogen mix homogeneously, put condensation back porphyrize admittedly, with 70g microcrystalline Cellulose mix homogeneously, with the 0.5%HPMC aqueous solution as binding agent system soft material, 12~20 order apertures are extruded into the bar, the bottom rotary speed that are about 3~5cm and are adjusted to 600~1200rpm, round as a ball about 5 minutes, get final product, drying, standby; Other gets Olmesartan and surplus microcrystalline Cellulose according to the equivalent principle mix homogeneously that sieves that progressively increases, and it is an amount of to add purified water, and the same method is prepared into micropill, and drying is standby.Proportionally, fill in the conventional capsule shell, promptly get above-mentioned slow releasing capsule behind two kinds of micropill mix homogeneously.
Embodiment 5 compound recipe metroprolol succinate Losartan Potassium matrix sustained release tablets
Matrix tablet label prescription:
Component | Content |
Metroprolol succinate HPMC-4M HPMC-15M microcrystalline Cellulose 90% ethanol is made altogether | An amount of 1000 of 100g 15 10g 25g |
Rapid release coatings prescription:
Component | Content |
Losartan Potassium Eudragit E (gastric solubleness) Pulvis Talci 80% ethanol | 50g 4g 2g 150ml |
Preparation method:
Metroprolol succinate is crossed 100 mesh sieves, and HPMC-4M, HPMC-15M cross 60 mesh sieves, and with 90% alcoholic solution system soft material, 16 mesh sieves are granulated, drying, 16 mesh sieve granulate, tabletting; Other gets Losartan Potassium and joins in Eudragit E 55 solution that prepare, and is standby; Regulate 30~50 ℃ of wind pressure 0.4~0.6bar, temperature, adjust rotary speed 150~200rpm, start peristaltic pump, spray into the suspendible coating solution of compositions such as containing Eudragit E, Losartan Potassium, after coating finished, discharging got final product.
Embodiment 6 compound hydrochloric acid metoprolol valsartan sustained release coating pellet capsules
Prescription:
Component | Content |
Metoprolol fumarate valsartan microcrystalline Cellulose Aquacoat purified water is made altogether | An amount of 1000 of 100g 80g 180g 18g |
Preparation method:
The hydrochloric acid metoprolol is crossed 100 mesh sieves, microcrystalline Cellulose is crossed 60 mesh sieves, get the hydrochloric acid metoprolol, with the microcrystalline Cellulose mix homogeneously of equivalent, add the wet soft material of an amount of system of purified water, 14~20 order apertures are extruded into the bar, the bottom rotary speed that are about 3~5cm and are adjusted to 800~1000rpm, round as a ball about 3~5 minutes, get final product, drying, standby; Other gets valsartan and the surplus microcrystalline Cellulose mix homogeneously that sieves, and it is an amount of to add purified water, and the same method is prepared into micropill, and drying is standby.Other gets the recipe quantity Aquacoat, adds suitable quantity of water and makes it to be uniformly dispersed, and is standby; Get hydrochloric metoprolol medicine carrying micropill, place the coating fluid bed, regulate 30~50 ℃ of wind pressure 0.4~0.6bar, temperature, adjust rotary speed 150~200rpm, start peristaltic pump, spray into the coating solution for preparing and carry out coating, make the hydrochloric acid metoprolol reach satisfied release in vitro effect, the coating after drying that finishes; Getting above exsiccant hydrochloric acid metoprolol coated micropill and valsartan medicine carrying micropill fills in the examples of suitable shell, promptly according to certain mixed.
Embodiment 7 compound hydrochloric acid metoprolol telmisartan slow-releasing granules capsules
Prescription:
Component | Content |
Metoprolol fumarate telmisartan Brazil wax glyceryl monostearate microcrystalline Cellulose amylodextrin magnesium stearate purified water is made altogether | An amount of 1000 of 75g 5g 30g 50g 15g 30g 10g 2g |
Preparation method:
The hydrochloric acid metoprolol is crossed 100 mesh sieves, and microcrystalline Cellulose is crossed 60 mesh sieves, mix homogeneously; In addition Brazil wax, glyceryl monostearate are added fusion, getting the above-mentioned hydrochloric acid metoprolol supplementary material that mixes joins wherein, continue to stir and to allow its slow cooling, scrape concretion, cross 16 mesh sieves and granulate, standby: other gets telmisartan, behind starch, dextrin mix homogeneously, add an amount of purified water system soft material, 18 mesh sieves are granulated, drying, 16 mesh sieve granulate; With above two kinds of granules mix homogeneously proportionally, add magnesium stearate, be filled in the suitable conventional capsule shell, promptly.
Claims (10)
1. a slow releasing preparation that contains heart selectivity β1Shou Tizuzhiji metoprolol and a kind of angiotensin ii receptor antagonist is characterized in that, this slow releasing preparation is made up of slow-released part and immediate release section.Wherein heart selectivity β1Shou Tizuzhiji metoprolol is a slow-released part, and angiotensin ii receptor antagonist is an immediate release section.
2. the described heart selectivity β1Shou Tizuzhiji of claim 1 metoprolol is characterized in that, can be that metoprolol is the salt of the various acid groups of active component, as tartrate, succinate, fumarate, maleate etc.; Described active component metoprolol can be left-handed optical isomer, dextrorotation optical isomer and raceme.
3. the described angiotensin ii receptor antagonist of claim 1, it is characterized in that, include but are not limited to irbesartan, Olmesartan, Candesartan, telmisartan, valsartan, Eprosartan, losartan isoreactivity composition, they can exist with the form of esters or salt.
4. the slow releasing preparation of claim 1, described active component metoprolol sustained-release part is characterized in that in the dissolution in vitro test that metoprolol stripping in the 1st hour discharges the 25~45%, 4th hour and discharges the 45~75%, 8th hour and discharges more than 75%.Described angiotensin ii receptor antagonist immediate release section, it is characterized in that its in dissolution in vitro test after 45 minutes stripping greater than 75%.
5. the described novel composing prescription of claim 1, it is characterized in that, include but are not limited to following combination: metoprolol+irbesartan, metoprolol+Olmesartan, metoprolol+candesartan Cilexetil, metoprolol+telmisartan, metoprolol+valsartan, metoprolol+Eprosartan, metoprolol+Losartan Potassium.
6. the described novel composing prescription of claim 1 is characterized in that, in described compound recipe, the unit dose of metoprolol is 100mg (in an active component); The unit dose of irbesartan is 0.075g~0.6g, is preferably 0.15g~0.30g; The unit dose of olmesartan medoxomil is 10mg~80mg, is preferably 20mg~40mg; The unit dose of candesartan Cilexetil is 1~24mg, is preferably 4~12mg; The unit dose of telmisartan is 10~80mg, is preferably 20~40mg; The unit dose of valsartan is 20~240mg, is preferably 80~160mg; The unit dose of Eprosartan is 200~800mg, is preferably 600mg; The unit dose of Losartan Potassium is 25~100mg, is preferably 50mg.
7. the described slow releasing preparation of claim 1~6 is characterized in that, can be slow releasing tablet, sustained-release granular formulation, slow-release pill, slow releasing capsule etc.Described slow releasing preparation comprises the delivery system that the coated formula of metoprolol sustained-release is formed by a sustained-release matrix or, and one can the rapid stripping of sartans delivery system.
8. the described sustained-release matrix of claim 7, it is characterized in that, comprise hydroxypropyl methylcellulose HPMC-4M, HPMC-15M, HPMC-100M, one or more in polyvinylpyrrolidone, ethyl cellulose, hydroxyethyl-cellulose, hexadecanol, octadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, sodium carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, the chitin.
9. the main slow releasing agent in the described coated formula of claim 7, it is characterized in that, comprise in ethyl cellulose and aqueous dispersion thereof, stearic acid, cellulose acetate, the crylic acid resin (as RS100, RL100, RS 30D, RL30D, NE30D) one or more.
10. the slow releasing preparation of the described new prescription of claim 1~9 is characterized in that, takes every day once, is used for the treatment of various types of hypertension symptoms.
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102145000A (en) * | 2010-02-06 | 2011-08-10 | 赤峰维康生化制药有限公司 | Candesartan cilexetil and metoprolol compound preparation |
CN102266295A (en) * | 2011-07-26 | 2011-12-07 | 北京阜康仁生物制药科技有限公司 | Controlled-release preparation for phosphopyridoxal buflomedil and preparation method thereof |
CN104928227A (en) * | 2015-05-21 | 2015-09-23 | 中国科学院化学研究所 | Application of conjugated polymer PFP-G2 |
CN105037692A (en) * | 2015-04-27 | 2015-11-11 | 中国科学院化学研究所 | Polythiophene, preparation method and application thereof |
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2007
- 2007-11-30 CN CNA2007101784961A patent/CN101185624A/en active Pending
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102145000A (en) * | 2010-02-06 | 2011-08-10 | 赤峰维康生化制药有限公司 | Candesartan cilexetil and metoprolol compound preparation |
CN102266295A (en) * | 2011-07-26 | 2011-12-07 | 北京阜康仁生物制药科技有限公司 | Controlled-release preparation for phosphopyridoxal buflomedil and preparation method thereof |
CN105037692A (en) * | 2015-04-27 | 2015-11-11 | 中国科学院化学研究所 | Polythiophene, preparation method and application thereof |
CN105037692B (en) * | 2015-04-27 | 2017-03-01 | 中国科学院化学研究所 | Polythiophene and preparation method and application |
CN104928227A (en) * | 2015-05-21 | 2015-09-23 | 中国科学院化学研究所 | Application of conjugated polymer PFP-G2 |
CN104928227B (en) * | 2015-05-21 | 2018-06-19 | 中国科学院化学研究所 | The application of conjugated polymer PFP-G2 |
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