CN101095682A - Oral preparations of ivabradine or the medical salt thereof - Google Patents
Oral preparations of ivabradine or the medical salt thereof Download PDFInfo
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- CN101095682A CN101095682A CNA2007101193622A CN200710119362A CN101095682A CN 101095682 A CN101095682 A CN 101095682A CN A2007101193622 A CNA2007101193622 A CN A2007101193622A CN 200710119362 A CN200710119362 A CN 200710119362A CN 101095682 A CN101095682 A CN 101095682A
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- ivabradine
- pharmaceutical salts
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- binding agent
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Abstract
The invention discloses a kind of oral product of ivabradine (Procoralan)or its medical salt, which can be produced into tablet, capsule and granule dosage form, which is characterized in that medical findings comprises filling agent, adhesive agent and lubricating agent, the weight ratio between ivabradine or its medical salt and medical filling agent is 1: 20-40; weight ratio between ivabradine or its medical salt and adhesive agent is 1: 1-2, and ivabradine or its medical salt and lubricating agent is 1: 0.2-0.4. It is showed by pharmacological experiment that the pharmacological action of ivabradine is very good.
Description
Technical field
The present invention relates to medical technical field, be specifically related to the oral formulations of a kind of Ivabradine or its pharmaceutical salts.
Background technology
The chronic stable angina pectoris is the modal clinical manifestation of chronic patients with coronary heart disease, and treatment in one's early years is conceived to mitigation symptoms and promptly alleviates and avoid angina pectoris attacks.What use in early days is the Nitrates medicine, the allevating angina pectoris outbreak rapidly of nitroglycerin sublingual administration, and long-acting nitric acid preparation then can prevent angina pectoris.The twentieth century 60 and the seventies, beta-blocker and calcium antagonist successively come out, and form the most frequently used clinically three major types antianginal drug at present with nitrate.The antianginal effect of this three classes medicine is similar, also all lacks the evidence that can reduce the patient with angina pectoris mortality rate or reduce main cardiovascular disease event.Some experts assert that by analyzing the data of fugitive nifedipine calcium antagonist is used for patients with coronary heart disease and can increases myocardial infarction danger and mortality rate.So, the safety of calcium antagonist falls under suspicion, and the status in angina pectoris treatment descends.As everyone knows, the stability angina pectoris is often with heart rate faster, therefore slow down the main target that heart rate is the treatment angina pectoris attacks, beta-blocker is the medicine of at present the most frequently used decreased heart rate, studies show that beta-blocker is relevant with its effect to heart rate to small part for the benefit of mortality rate, comprises ischemic heart desease and chronic heart failure.But there are many contraindications in the application of beta-blocker, comprises airway obstruction, atrioventricular block, the compensatory heart failure of mistake, symptomatic peripheral blood vessel etc.Therefore, specificity reduces the medicine of heart rate, as the If inhibitor, more and more is subjected to the attention of researcher.
Ivabradine is first specificity If inhibitor, and be first pure decreased heart rate medicine, suppress heartpacer If by selectivity and press down (be controlled at the spontaneous diastole depolarization in the sinuatrial node and regulate heart rate) electric current, the selective effect of sinuatrial node is not had effect to conduction in the heart, myocardial contraction or ventricular bipolarization.This product is different with the most frequently used B receptor blocking agent of treatment angina pectoris, does not influence libido, respiratory tract contraction or untoward reaction or rebound phenomenons such as spasm, bradycardia do not occur.The effect of this simple decreased heart rate of Ivabradine is expected to become the new selection of current Therapeutic Method.Therefore, Ivabradine or its pharmaceutical salts being prepared into preparation being used for clinically, is a lot of medical scientific research personnel's urgent problem.
Up to the present, in the preparation of tablet, capsule, granule, also not finding has any medicine, directly is prepared into preparation without pharmaceutic adjuvant, and therefore, the selection of medicinal adjuvant in the R﹠D process of preparation has very important effect; The pharmaceutic adjuvant of tablet, capsule, granule comprises: disintegrating agent, filler, binding agent, lubricant etc., particularly the selection of disintegrating agent is most important, has only and selects suitable disintegrants can make the disintegrate of medicine and stripping meet the requirements (Chinese Pharmacopoeia version regulation in 2005 oral solid formulation in the time of 45 minutes dissolution will reach more than 75%); Ivabradine or its pharmaceutical salts are prepared into tablet, capsule, granule, select suitable pharmaceutic adjuvant, just can be prepared into qualified finished product preparation according to the character of principal agent.
Summary of the invention
For these reasons, our scientific research personnel finds under study for action: when Ivabradine or its pharmaceutical salts are prepared into tablet, capsule, granule, pharmaceutic adjuvant only need add filler, binding agent, lubricant, and without any need for disintegrating agent, just can prepare qualified Ivabradine or its pharmaceutical salts oral formulations, the selection of such pharmaceutic adjuvant has reduced the pharmaceutic adjuvant use amount, save production cost, reduced patient's dose.
The application's Ivabradine is as follows:
Adopted name: Ivabradine
The Chinese chemical name: 3-{3-[{[(7S)-3,4-dimethoxy dicyclo [4.2.0] suffering-1,3,5-triolefin-7-yl]-methyl } (methyl) amino] propyl group }-7,8-dimethoxy-1,3,4,5-tetrahydrochysene-2H-3-benzo-aza-2-ketone
Molecular formula: C
27H
36N
2O
5
The application realizes by following experimental program.
A kind of Ivabradine or its pharmaceutical salts oral formulations comprise Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant, are prepared into tablet, capsule, granule, it is characterized in that pharmaceutic adjuvant is filler, binding agent and lubricant.
Wherein the pharmaceutic adjuvant filler is one or more in lactose, sucrose, glucose, mannitol, sorbitol, sodium chloride, fructose, polyvidone, starch (moisture 10%-15%), calcium hydrogen phosphate, calcium sulfate, the calcium carbonate.
Wherein binding agent is one or more in dextrin, Macrogol 4000, methylcellulose, sodium carboxymethyl cellulose, the gelatin.
Wherein lubricant is one or more in magnesium stearate, silicon dioxide, the Pulvis Talci.
Wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant filler is 1: 20-40; The weight ratio of preferred Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant filler is 1: 28.1.
Wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant binding agent is 1: 1-2; The weight ratio of preferred Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant binding agent is 1: 1.55.
Wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant lubricant is 1: 0.2-0.4; The weight ratio of preferred Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant lubricant is 1: 0.31.
Wherein tablet, capsule, 45 minutes dissolutions of granule are more than or equal to 80% and less than 100%.
One, dissolution determination method
Experimental technique: according to (two appendix XC of Chinese Pharmacopoeia version in 2005) (three therapeutic methods of traditional Chinese medicine), be medium with the water of 200ml, rotating speed is that per minute 50 changes, and sampling 10ml filters in the time of 45 minutes, gets subsequent filtrate as need testing solution; Measure stripping quantity, limit is 80% of a labelled amount, should be up to specification.It is an amount of that other gets the hydrochloric acid Ivabradine reference substance, and accurate the title decides, and adds stripping medium 20ml, and ultrasonic 5min makes the hydrochloric acid Ivabradine dissolving, makes the solution that contains Ivabradine 25 μ g among every 1ml with the dissolution medium dilution.Get reference substance and need testing solution, measure trap at the 286nm place with the uv-spectrophotometric instrument.Calculate dissolution.
Experimental result: the application's tablet, capsule, granule in the time of 45 minutes dissolution more than or equal to 80% and less than 100%.
Two, the selection of pharmaceutic adjuvant
Experimental program 1: get Ivabradine or its pharmaceutical salts crushing screening, get filler, the disintegrating agent pulverize separately sieves, mix homogeneously, equivalent adds Ivabradine or its pharmaceutical salts, mixing, system soft material, granulation, granulate add lubricant, are prepared into preparation according to the conventional preparation method of the pharmaceutics of tablet, capsule, granule;
Experimental result: the mobility of particle of above-mentioned experimental program preparation is better, but it is looser, frangible to obtain granule, need bigger pressure during tabletting, also be unfavorable for the preservation of granule and capsule, can't prepare qualified finished product preparation, and not add binding agent in the above-mentioned experimental program, therefore, need further to revise experimental program;
Experimental program 2: get Ivabradine or its pharmaceutical salts crushing screening, getting filler, disintegrating agent, binding agent pulverize separately sieves, mix homogeneously, equivalent adds Ivabradine or its pharmaceutical salts, mixing, system soft material, granulation, granulate add lubricant, are prepared into preparation according to the conventional preparation method of the pharmaceutics of tablet, capsule, granule;
Experimental result: above-mentioned experimental program grain forming is better, non-friable, but mobile bad, angle of repose is bigger, can't prepare qualified finished product preparation, points out us to continue to improve experimental program;
Experimental program 3: get Ivabradine or its pharmaceutical salts crushing screening, get filler, the binding agent pulverize separately sieves, mix homogeneously, equivalent adds Ivabradine or its pharmaceutical salts, mixing, system soft material, granulation, granulate add lubricant, are prepared into preparation according to the conventional preparation method of the pharmaceutics of tablet, capsule, granule;
Experimental result: above-mentioned experimental program does not add disintegrating agent, made mobility of particle is better, spend angle of reposes 29, dissolution meets the requirements, point out us to have associated with the physicochemical properties of Ivabradine or its pharmaceutical salts and disintegrating agent, after not adding disintegrating agent, preparation meets every requirement, can prepare qualified finished product preparation, therefore, we think that experimental program 3 pharmaceutic adjuvants only select filler, binding agent, lubricant, and do not add disintegrating agent, to the not influence of every indexs such as dissolution of preparation, illustrative experiment scheme 3 can be used for preparing Ivabradine or its pharmaceutical salts preparation.
Three, pharmaceutic adjuvant confirmatory experiment
Experimental program 1: Ivabradine or its pharmaceutical salts: filler=1: 20, Ivabradine or its pharmaceutical salts: binding agent=1: 1, Ivabradine or its pharmaceutical salts: lubricant=1: 0.2;
Experimental program 2: Ivabradine or its pharmaceutical salts: filler=1: 40, Ivabradine or its pharmaceutical salts: binding agent=1: 2, Ivabradine or its pharmaceutical salts: lubricant=1: 0.4;
Experimental program 3: Ivabradine or its pharmaceutical salts: filler=1: 28.1, Ivabradine or its pharmaceutical salts: binding agent=1: 1.42, Ivabradine or its pharmaceutical salts: lubricant=1: 0.28;
Experimental program 4: Ivabradine or its pharmaceutical salts: filler=1: 30, Ivabradine or its pharmaceutical salts: binding agent=1: 1.55, Ivabradine or its pharmaceutical salts: lubricant=1: 0.29;
Experimental program 5: Ivabradine or its pharmaceutical salts: filler=1: 31, Ivabradine or its pharmaceutical salts: binding agent=1: 1.49, Ivabradine or its pharmaceutical salts: lubricant=1: 0.31;
Experimental program 6: Ivabradine or its pharmaceutical salts: filler=1: 28.1, Ivabradine or its pharmaceutical salts: binding agent=1: 1.55, Ivabradine or its pharmaceutical salts: lubricant=1: 0.31;
Experimental program 7: Ivabradine or its pharmaceutical salts: filler=1: 22, Ivabradine or its pharmaceutical salts: binding agent=1: 1.28, Ivabradine or its pharmaceutical salts: lubricant=1: 0.24;
Experimental program 8: Ivabradine or its pharmaceutical salts: filler=1: 37, Ivabradine or its pharmaceutical salts: binding agent=1: 1.82, Ivabradine or its pharmaceutical salts: lubricant=1: 0.37;
Experimental technique: get Ivabradine or its pharmaceutical salts crushing screening, get filler, the binding agent pulverize separately sieves, mix homogeneously, equivalent adds Ivabradine or its pharmaceutical salts, mixing, system soft material, granulation, granulate detect particulate flowability, angle of repose, add lubricant, be prepared into preparation according to the conventional preparation method of the pharmaceutics of tablet, capsule, granule; According to the detection method of dissolution in the present specification, measure 45 minutes dissolution of preparation, experimental result sees Table 1:
Table 1 different experiments scheme relatively
| Group | Mobility of particle | The angle of stopping | 45 minutes dissolution % |
| Scheme 1 scheme 2 schemes 3 schemes 4 schemes 5 schemes 6 schemes 7 | Carefully fine good | 30 31 29 29 29 28 30 | 82.3 85.7 87.6 88.3 87.1 92.7 84.9 |
| Scheme 8 | Good | 30 | 85.0 |
Experiment conclusion: show by above-mentioned experiment: the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant filler is 1: 20-40; The weight ratio of preferred Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant filler is 1: 28.1; The weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant binding agent is 1: 1-2; The weight ratio of preferred Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant binding agent is 1: 1.55; Cutting down mine-laying weight ratio fixed or its pharmaceutical salts and pharmaceutic adjuvant lubricant is 1: 0.2-0.4; The weight ratio of preferred Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant lubricant is 1: 0.31.
Five, pharmacological experiment
(1) to the effect in isolated rat atrium
5.5 * 10
-7Mol/L-5.5 * 10
-6The Ivabradine of mol/L can reduce the spontaneity fight rate of isolated rat right atrium, 2.1 * 10 in concentration dependence mode
-6Suppression ratio during mol/L is 30%.10
-6The inhibitory action of medicine is very remarkable during mol/L, is-20.0 ± 3.8%, 5.5 * 10
-6Inhibitory action during mol/L is the strongest, is-40.6 ± 2.9%.Drug treating maximum inhibitory action promptly occurred after 15,20 minutes.Atropine can not significantly change the AR reduction effect of Ivabradine, and the effect of inferring this product thus is not the M-ChR mediation.
With 10
-9Mol/L-5.5 * 10
-8The mol/L isopropyl noradrenalin is handled the isolated rat right atrium, uses 3 * 10 subsequently
-6The mol/L Ivabradine is handled.Result: compare with contrast ratio, under the stimulation of isopropyl noradrenalin, this product can reduce the foundation rate (34.1 ± 2.3%) in atrium, and sustainable this effect, but this product is to the not influence of the stimulation of 50% effective dose isopropyl noradrenalin, infers that thus this product do not have the beta-adrenergic blocking activity.
(2) to the electrophysiologic testing of rabbit sinuatrial node
This product reduces the spontaneous frequency of action potential in concentration dependence mode, and 0.1 μ M Ivabradine handles rabbit sinuatrial node 3h or 1 μ M handles 40min, observes discharge rate and reduces 9-12%.All concentration (0.03-1 μ M) that detect all can cause diastole depolarization slope to reduce.But the activation of do not have the greatest impact diastole current potential or threshold potential.Study the selection inhibition of this product to the If electric current at the sinus node cells of rabbit, the result shows that this product has very high selection inhibition.1.5-3 μ M (suppresses If electric current I C
50Concentration) Ivabradine is to ICa, L, and ICa, T and IK electric current is effect not.
(3) in vivo test
To anaesthetizing, open pig continuous intravenous injection 0.1,0.3, the 1mg/kg Ivabradine in thoracic cavity, the result presents effectively, the reduction heart rate function of dose dependent (16-37%), but does not influence myocardial contraction, ventricular bipolarization (QTc), chamber conduction (PR interval).Ivabradine shrinks not influence to blood pressure, periphery and vascular resistance, left ventricle.
To the male dog intravenously administrable, 0.5, heart rate descended 16%, 25%, 0.3 when the 1mg/kg Ivabradine made tranquillization respectively, the 1mg/kg Ivabradine makes exercise heart rate descend 10%, 30% respectively.
Ivabradine to the reduction of the increase of average coronary blood flow speed and coronary artery resistance all less than influence.Not effect of epicardial coronary arteries parameter when simultaneously this product is to tranquillization, but the increase of epicardial coronary arteries parameter when having strengthened motion.
Six, preparation embodiment
Embodiment 1
Ivabradine or its pharmaceutical salts 5 grams, filler lactose 100 grams, binding agent Macrogol 4000 5 grams, lubricant Pulvis Talci 1 gram;
Get Ivabradine or its pharmaceutical salts crushing screening; get filler, the binding agent pulverize separately sieves; mix homogeneously; equivalent adds Ivabradine or its pharmaceutical salts; mixing; system soft material, granulation, granulate add lubricant, according to the conventional preparation method of pharmaceutics be prepared into 1000 bags of 1000 in tablet or 1000 of capsules or granules.
Embodiment 2
Ivabradine or its pharmaceutical salts 5 grams, filler lactose, sucrose, glucose, mannitol, calcium hydrogen phosphate, calcium sulfate is totally 200 grams, and binding agent methylcellulose, sodium carboxymethyl cellulose, gelatin be totally 10 grams, and lubricant Pulvis Talci, magnesium stearate be totally 2 grams;
Get Ivabradine or its pharmaceutical salts crushing screening; get filler, the binding agent pulverize separately sieves; mix homogeneously; equivalent adds Ivabradine or its pharmaceutical salts; mixing; system soft material, granulation, granulate add lubricant, according to the conventional preparation method of pharmaceutics be prepared into 1000 bags of 1000 in tablet or 1000 of capsules or granules.
Embodiment 3
Ivabradine or its pharmaceutical salts 5.39 grams, filler lactose, starch is totally 151.56 grams, and the binding agent dextrin is totally 8.35 grams, and lubricant silicon dioxide, magnesium stearate be totally 1.70 grams;
Get Ivabradine or its pharmaceutical salts crushing screening; get filler, the binding agent pulverize separately sieves; mix homogeneously; equivalent adds Ivabradine or its pharmaceutical salts; mixing; system soft material, granulation, granulate add lubricant, according to the conventional preparation method of pharmaceutics be prepared into 1000 bags of 1000 in tablet or 1000 of capsules or granules.
Embodiment 4
Ivabradine or its pharmaceutical salts 5.39 grams, filler sorbitol, sodium chloride, calcium carbonate be totally 151.56 grams, and binding agent Macrogol 4000, methylcellulose be totally 7.98 grams, and lubricant silicon dioxide, magnesium stearate, Pulvis Talci be totally 1.56 grams;
Get Ivabradine or its pharmaceutical salts crushing screening; get filler, the binding agent pulverize separately sieves; mix homogeneously; equivalent adds Ivabradine or its pharmaceutical salts; mixing; system soft material, granulation, granulate add lubricant, according to the conventional preparation method of pharmaceutics be prepared into 1000 bags of 1000 in tablet or 1000 of capsules or granules.
Embodiment 5
Ivabradine or its pharmaceutical salts 5.39 grams, filler polyvidone, calcium hydrogen phosphate, calcium sulfate is totally 159.00 grams, binding agent dextrin, Macrogol 4000, methylcellulose, sodium carboxymethyl cellulose be totally 8.35 grams, and lubricant silicon dioxide, Pulvis Talci be totally 1.64 grams;
Get Ivabradine or its pharmaceutical salts crushing screening; get filler, the binding agent pulverize separately sieves; mix homogeneously; equivalent adds Ivabradine or its pharmaceutical salts; mixing; system soft material, granulation, granulate add lubricant, according to the conventional preparation method of pharmaceutics be prepared into 1000 bags of 1000 in tablet or 1000 of capsules or granules.
Embodiment 6
Ivabradine or its pharmaceutical salts 5.39 grams, filler glucose, calcium hydrogen phosphate, calcium sulfate, calcium carbonate be totally 148.9 grams, and binding agent dextrin, gelatin be totally 8.17 grams, and lubricant silicon dioxide, magnesium stearate be totally 1.70 grams;
Get Ivabradine or its pharmaceutical salts crushing screening; get filler, the binding agent pulverize separately sieves; mix homogeneously; equivalent adds Ivabradine or its pharmaceutical salts; mixing; system soft material, granulation, granulate add lubricant, according to the conventional preparation method of pharmaceutics be prepared into 1000 bags of 1000 in tablet or 1000 of capsules or granules.
Embodiment 7
Ivabradine or its pharmaceutical salts 5.39 grams, filler sorbitol, sodium chloride, fructose, polyvidone, starch, calcium hydrogen phosphate, calcium sulfate, calcium carbonate be totally 129.36 grams, binding agent essence, methylcellulose, sodium carboxymethyl cellulose be totally 7.44 grams, and magnesium stearate lubricant is totally 1.27 grams;
Get Ivabradine or its pharmaceutical salts crushing screening; get filler, the binding agent pulverize separately sieves; mix homogeneously; equivalent adds Ivabradine or its pharmaceutical salts; mixing; system soft material, granulation, granulate add lubricant, according to the conventional preparation method of pharmaceutics be prepared into 1000 bags of 1000 in tablet or 1000 of capsules or granules.
Embodiment 8
Ivabradine or its pharmaceutical salts 5.39 grams, filler calcium hydrogen phosphate 199.4 grams, binding agent methylcellulose 9.75 grams, lubricant silicon dioxide, magnesium stearate, Pulvis Talci be totally 2.04 grams;
Get Ivabradine or its pharmaceutical salts crushing screening; get filler, the binding agent pulverize separately sieves; mix homogeneously; equivalent adds Ivabradine or its pharmaceutical salts; mixing; system soft material, granulation, granulate add lubricant, according to the conventional preparation method of pharmaceutics be prepared into 1000 bags of 1000 in tablet or 1000 of capsules or granules.
Annotate: the present invention's concrete technical scheme required for protection is not limited to the concrete combination of the expressed technical scheme of the foregoing description.
Claims (11)
1, the oral formulations of a kind of Ivabradine or its pharmaceutical salts comprises Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant, is prepared into tablet, capsule, granule, it is characterized in that pharmaceutic adjuvant is filler, binding agent and lubricant.
2, the formulation of a kind of Ivabradine according to claim 1 or its pharmaceutical salts mouth, wherein the pharmaceutic adjuvant filler is one or more in lactose, sucrose, glucose, mannitol, sorbitol, sodium chloride, fructose, polyvidone, starch, calcium hydrogen phosphate, calcium sulfate, the calcium carbonate.
3, the oral formulations of a kind of Ivabradine according to claim 1 or its pharmaceutical salts, wherein binding agent is one or more in dextrin, Macrogol 4000, methylcellulose, sodium carboxymethyl cellulose, the gelatin.
4, the oral formulations of a kind of Ivabradine according to claim 1 or its pharmaceutical salts, wherein lubricant is one or more in magnesium stearate, silicon dioxide, the Pulvis Talci.
5, the oral formulations of a kind of Ivabradine according to claim 1 or its pharmaceutical salts, wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant filler is 1: 20-40.
6, the oral formulations of a kind of Ivabradine according to claim 1 or its pharmaceutical salts, wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant binding agent is 1: 1-2.
7, the oral formulations of a kind of Ivabradine according to claim 1 or its pharmaceutical salts, wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant lubricant is 1: 0.2-0.4.
8, the oral formulations of a kind of Ivabradine according to claim 1 or its pharmaceutical salts, wherein tablet, capsule, 45 minutes dissolutions of granule are more than or equal to 80% and less than 100%.
9, the oral formulations of a kind of Ivabradine according to claim 5 or its pharmaceutical salts, wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant filler is 1: 28.1.
10, the oral formulations of a kind of Ivabradine according to claim 6 or its pharmaceutical salts, wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant binding agent is 1: 1.55.
11, the oral formulations of a kind of Ivabradine according to claim 7 or its pharmaceutical salts, wherein the weight ratio of Ivabradine or its pharmaceutical salts and pharmaceutic adjuvant lubricant is 1: 0.31.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101193622A CN101095682A (en) | 2007-07-23 | 2007-07-23 | Oral preparations of ivabradine or the medical salt thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101193622A CN101095682A (en) | 2007-07-23 | 2007-07-23 | Oral preparations of ivabradine or the medical salt thereof |
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| CNA2007101193622A Pending CN101095682A (en) | 2007-07-23 | 2007-07-23 | Oral preparations of ivabradine or the medical salt thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101897682A (en) * | 2010-07-13 | 2010-12-01 | 石药集团欧意药业有限公司 | Ivabradine preparation or ivabradine medicinal salt solid preparation and preparation method thereof |
| CN101507726B (en) * | 2008-02-14 | 2012-03-28 | 瑟维尔实验室 | Association of a sinus If current inhibitor and a beta blocker |
| CN106265582A (en) * | 2016-08-31 | 2017-01-04 | 辰欣药业股份有限公司 | A kind of hydrochloric acid Ivabradine sheet and preparation technology thereof |
-
2007
- 2007-07-23 CN CNA2007101193622A patent/CN101095682A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101507726B (en) * | 2008-02-14 | 2012-03-28 | 瑟维尔实验室 | Association of a sinus If current inhibitor and a beta blocker |
| CN101897682A (en) * | 2010-07-13 | 2010-12-01 | 石药集团欧意药业有限公司 | Ivabradine preparation or ivabradine medicinal salt solid preparation and preparation method thereof |
| CN106265582A (en) * | 2016-08-31 | 2017-01-04 | 辰欣药业股份有限公司 | A kind of hydrochloric acid Ivabradine sheet and preparation technology thereof |
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Open date: 20080102 |