CN101637442A - Ranolazine oral sustained-release preparation and preparation method thereof - Google Patents
Ranolazine oral sustained-release preparation and preparation method thereof Download PDFInfo
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- CN101637442A CN101637442A CN200810135326A CN200810135326A CN101637442A CN 101637442 A CN101637442 A CN 101637442A CN 200810135326 A CN200810135326 A CN 200810135326A CN 200810135326 A CN200810135326 A CN 200810135326A CN 101637442 A CN101637442 A CN 101637442A
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Abstract
The invention provides a Ranolazine oral sustained-release preparation and a preparation method. The Ranolazine oral sustained-release preparation comprises Ranolazine, a sustained-release skeleton material, a filling agent, an adhesive and a lubricating agent, and is characterized in that the weight of the Ranolazine is between 35 and 85 percent in the sustained-release preparation; a prescription composition is preferably selected according to a large number of experiments; hydroxypropyl methyl cellulose phthalate and methyl cellulose are served as the sustained-release skeleton material ofthe sustained-release preparation in the preferable weight ratio of 2:1-1.5; and microcrystalline cellulose is served as the filling agent; the 29/39 ethanol solution of polyvinyl pyrrolidone K is served as the adhesive, and magnesium stearate is served as the lubricating agent.
Description
Invention field:
The invention belongs to the drug technique invention field, relate to slow releasing preparation that contains ranolazine and preparation method thereof.
Technical background:
Angina pectoris is the common sympton of coronary heart disease, is again the signal of interest of finding coronary heart disease.At present domesticly be usually used in treating antianginal medicine such as propranolol, nifedipine, sorbitrate etc. clinically, all the patient had dependency, complication in various degree or causes the constitutional disorder.Ideal antianginal drug should both can reduce the myocardial metabolism oxygen demand, again can coronary blood flow increasing, it is all effective to symptom and silent ischemia are arranged, and the patient is easy to accept, and allows the patient to keep certain physical exertion, and can merge use with other drug, should not cause toleration, do not cause postural hypotension, left ventricular function and conducting system of heart are had no side effect, preferably metabolism that can be useful and antithrombotic and antiplatelet effects.This direction effort of the design forward of novel anti angina drug.And the ranolazine representative medicine of this novel anti angina drug just.
Ranolazine is developed by U.S. CV Therapeutics company, belong to the partial fatty acid oxidation enzyme inhibitor, it is a kind of new drug in the metabolism therapy of resisting myocardial ischemia, be mainly used in treatment clinically and comprise the angina pectoris that arrhythmia, variability and mobility bring out, and the cardiovascular disease due to the myocardial infarction.The ranolazine mechanism of action is to reduce the heart oxygen demand by enzyme regulation, improves the imbalance between the oxygen supply and demand, alleviates the symptom of regional myocardial ischemia.In addition, ranolazine also can be strengthened the glucose oxidase effect, thereby be increased the heart coefficient of oxygen utilization by regulating the metabolism of body when reducing the free fatty Oxidation.The difference of ranolazine and other treatment medicine is that it does not influence heart rate or blood pressure in the effect of performance antianginal.Ranolazine can be as adjuvant therapy medicaments and with the antianginal drug use in conjunction of other recommendations, help the control of disease and reach whole therapeutic goals.
Because of the increase of its dissolubility with body fluid pH reduces, this product plasma half-life is shorter simultaneously, causes therapeutic process to need frequent drug administration thus, patient's medication poor compliance.For this reason, these product are carried out slow releasing preparation research, most typical preparation is a slow releasing tablet, and the ranolazine sustained release tablet recipe is designed and is optimized and technical study.
Summary of the invention:
One of purpose of the present invention provides a kind of ranolazine oral sustained-release preparation, is used for the treatment of chronic stable angina pectoris; Another object of the present invention provides this medicament slow release preparation preparation method.
The present invention seeks to realize by following technical solution
The invention provides a kind of ranolazine oral sustained-release preparation, comprise ranolazine, sustained-release matrix material, filler, binding agent and lubricant, it is characterized in that the weight of ranolazine in slow releasing preparation is 35%-85%.According to purpose of the present invention, we are when the preparation method of research ranolazine sustained release tablets, optimizing prescription according to a large amount of tests forms, we are hydroxypropylmethyl cellulose phthalate and the methylcellulose sustained-release matrix material as slow releasing preparation of the present invention, and to optimize its weight ratio be 2: 1-1.5; Microcrystalline Cellulose is filled agent as adding, and polyethylene adjoins pyrrolidone K29/30 alcoholic solution as binding agent, selects magnesium stearate as lubricant.
We adopt orthogonal design to filter out best preparation process condition.Hardness according to hydroxypropylmethyl cellulose phthalate (HPMCP), methylcellulose (MC) and microcrystalline Cellulose (PH101) consumption and slow releasing tablet is that factor is tested, determine the best preparation technology part of being engaged in, and the result of the test of optimizing verified, investigate its release in vitro effect simultaneously.Optimum process condition HPMCP, MC, PH101 consumption are respectively 150,75,30mg, tabletting hardness 10kg; Prepared ranolazine sustained release tablets 2,6, the cumulative in vitro release rate of 12h is respectively (29.33 ± 1.05) %, (59.93 ± 1.53) %, (95.60 ± 1.31) %.
A kind of ranolazine oral sustained-release preparation of the present invention is characterized in that this slow releasing preparation is the skeleton slow releasing tablet, and label has Opadry (Opadry II) damp-proof membrane outward; The every monolithic of this slow releasing tablet contains the slow-release material of following weight: hydroxypropylmethyl cellulose phthalate 100mg-200mg, methylcellulose 40mg-100mg and microcrystalline Cellulose 10mg-50mg forms.
We preferentially choose the consumption of slow-release material according to experiment, and hydroxypropylmethyl cellulose phthalate 150mg, methylcellulose 75mg and microcrystalline Cellulose 30mg form.
A kind of ranolazine oral sustained-release preparation of the present invention is characterized in that it can being pharmaceutically acceptable dosage form such as slow releasing tablet, slow release ball, slow releasing capsule.
Another one purpose of the present invention provides a kind of preparation method of ranolazine oral sustained-release preparation, it is characterized in that preparation method is as follows:
Ranolazine, hydroxypropylmethyl cellulose phthalate, methylcellulose and the microcrystalline Cellulose pulverize separately of recipe quantity are also crossed 100 mesh sieves, mix homogeneously, add an amount of polyvinylpyrrolidone K29/30 alcoholic solution system soft material, granulate, in 50 ℃ of oven dry, granulate, add carboxymethyl starch sodium and magnesium stearate, mix homogeneously, tabletting, coating, promptly.
Following experimental example is used to further specify the present invention:
565 routine patients accept this product predose (500mg 2 times on the one) at random or placebo took for 1 week, take this product 1000mg subsequently 6 weeks 2 times on the one or placebo.Meanwhile all take amlodipine 10mg 4 times on the one, 45% patient also accepts long-acting nitrate esters medicine.During angina pectoris attacks as required the Sublingual give nitrate esters medicine.The result shows that this product group significantly reduces (P=0.028) than placebo group angina pectoris incidence rate, and nitroglycerin is taken number of times and also significantly lowered (P=0.014).
Test example 2,
Chronic patient with angina pectoris 175 examples (wherein 29 people have the heart failure medical history) give all placebo, ranolazine 500mg, 1000mg and 1500mg respectively.In each end of term in week of 4 treatment cycle, the patient is carried out exercise tolerance test, found that all patient's symptoms significantly improve, and be dose dependent that wherein 29 routine patients with heart failure improve the most obvious.
Specific implementation method
Further specify technical scheme of the present invention below by specific embodiment
Embodiment 1:
Ranolazine 200g
Hydroxypropylmethyl cellulose phthalate 150g
Methylcellulose 100g
Microcrystalline Cellulose 50g
Polyvinylpyrrolidone K29/30 20g
Magnesium stearate 15g
Make 1000
Preparation method:
Ranolazine, hydroxypropylmethyl cellulose phthalate, methylcellulose and the microcrystalline Cellulose pulverize separately of recipe quantity are also crossed 100 mesh sieves, mix homogeneously, polyvinylpyrrolidone K29 is added an amount of dehydrated alcohol system soft material, granulate, in 50 ℃ of oven dry, granulate, add carboxymethyl starch sodium and magnesium stearate, mix homogeneously, tabletting, coating, promptly.
Indication: treatment chronic stable angina pectoris.
Usage and dosage: each 2-4 sheet, every day 2-3 time.
Slow releasing tablet embodiment 2:
Ranolazine 300g
Hydroxypropylmethyl cellulose phthalate 150g
Methylcellulose 75g
Microcrystalline Cellulose 30g
Polyvinylpyrrolidone K29/30 20g
Magnesium stearate 10g
Make 1000
Preparation method:
Ranolazine, hydroxypropylmethyl cellulose phthalate, methylcellulose 75mg and the microcrystalline Cellulose pulverize separately of recipe quantity are also crossed 100 mesh sieves, mix homogeneously, polyvinylpyrrolidone K29 is added an amount of dehydrated alcohol system soft material, granulate, in 50 ℃ of oven dry, granulate, add carboxymethyl starch sodium and magnesium stearate, mix homogeneously, tabletting, coating, promptly
Indication: treatment chronic stable angina pectoris.
Usage and dosage: each 2-3 sheet, every day 2-3 time.
Slow releasing tablet embodiment 3:
Ranolazine 350g
Hydroxypropylmethyl cellulose phthalate 75g
Methylcellulose 40g
Microcrystalline Cellulose 20g
Polyvinylpyrrolidone K29/30 10g
Magnesium stearate 5g
Preparation method:
Ranolazine, hydroxypropylmethyl cellulose phthalate, methylcellulose and the microcrystalline Cellulose pulverize separately of recipe quantity are also crossed 100 mesh sieves, mix homogeneously, polyvinylpyrrolidone K29 is added an amount of dehydrated alcohol system soft material, granulate, in 50 ℃ of oven dry, granulate, add carboxymethyl starch sodium and magnesium stearate, mix homogeneously, tabletting, coating, promptly
Indication: treatment chronic stable angina pectoris.
Usage and dosage: each 2-4 sheet, every day 2-3 time.
Slow releasing tablet embodiment 4:
Ranolazine 500g
Hydroxypropylmethyl cellulose phthalate 50g
Methylcellulose 20g
Polyvinylpyrrolidone K29/30 10g
Magnesium stearate 5g
Make 1000
Preparation method:
Ranolazine, hydroxypropylmethyl cellulose phthalate, methylcellulose and the microcrystalline Cellulose pulverize separately of recipe quantity are also crossed 100 mesh sieves, mix homogeneously, polyvinylpyrrolidone K29 is added an amount of dehydrated alcohol system soft material, granulate, in 50 ℃ of oven dry, granulate, add carboxymethyl starch sodium and magnesium stearate, mix homogeneously, tabletting, coating, promptly.
Indication: treatment chronic stable angina pectoris.
Usage and dosage: each 2-3 sheet, every day 1-2 time.
Claims (7)
1. a ranolazine oral sustained-release preparation comprises ranolazine, sustained-release matrix material, filler, binding agent and lubricant, it is characterized in that the weight of ranolazine in slow releasing preparation is 35%-85%.
2. a kind of according to claim 1 ranolazine oral sustained-release preparation is characterized in that this slow releasing preparation is the skeleton slow releasing tablet, and label has Opadry (Opadry II) damp-proof membrane outward.
3. a kind of as claimed in claim 1 or 2 ranolazine oral sustained-release preparation, the sustained-release matrix material that it is characterized in that this slow releasing preparation are that hydroxypropylmethyl cellulose phthalate and methylcellulose are formed, and its weight ratio is 2: 1-1.5; Filler is a microcrystalline Cellulose, and binding agent is that polyethylene adjoins pyrrolidone K29/30 alcoholic solution, and lubricant is a magnesium stearate.
4. as a kind of ranolazine oral sustained-release preparation as described in claim 2 or 3, it is characterized in that the every monolithic of this slow releasing tablet contains the slow-release material of following weight: hydroxypropylmethyl cellulose phthalate 50mg-150mg, methylcellulose 20mg-100mg and microcrystalline Cellulose 5mg-15mg forms.
5. as a kind of ranolazine oral sustained-release preparation as described in the claim 4, it is characterized in that the every monolithic of this slow releasing tablet contains the slow-release material of following weight: hydroxypropylmethyl cellulose phthalate 100mg, methylcellulose 75mg and microcrystalline Cellulose 10mg forms.
6. a kind of according to claim 1 ranolazine oral sustained-release preparation is characterized in that it can being pharmaceutically acceptable dosage form such as slow releasing tablet, slow release ball, slow releasing capsule.
7. the preparation method of a ranolazine oral sustained-release preparation is characterized in that preparation method is as follows:
Ranolazine, hydroxypropylmethyl cellulose phthalate, methylcellulose and the microcrystalline Cellulose pulverize separately of recipe quantity are also crossed 100 mesh sieves, mix homogeneously, add an amount of polyvinylpyrrolidone K29/30 alcoholic solution system soft material, granulate, in 50 ℃ of oven dry, granulate, add carboxymethyl starch sodium and magnesium stearate, mix homogeneously, tabletting, coating, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN200810135326A CN101637442A (en) | 2008-07-30 | 2008-07-30 | Ranolazine oral sustained-release preparation and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN200810135326A CN101637442A (en) | 2008-07-30 | 2008-07-30 | Ranolazine oral sustained-release preparation and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017001669A1 (en) | 2015-07-02 | 2017-01-05 | Interquim, S.A. | Ranolazine multiple compressed tablets |
| WO2018001582A1 (en) | 2016-06-30 | 2018-01-04 | Interquim, S.A. | Ranolazine multiple compressed tablets |
| CN110882316A (en) * | 2019-12-23 | 2020-03-17 | 卓和药业集团有限公司 | Compound preparation of anti-angina pectoris medicine and preparation method thereof |
| CN110898024A (en) * | 2019-12-17 | 2020-03-24 | 卓和药业集团有限公司 | Pharmaceutical composition for treating angina pectoris and preparation method thereof |
-
2008
- 2008-07-30 CN CN200810135326A patent/CN101637442A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017001669A1 (en) | 2015-07-02 | 2017-01-05 | Interquim, S.A. | Ranolazine multiple compressed tablets |
| WO2018001582A1 (en) | 2016-06-30 | 2018-01-04 | Interquim, S.A. | Ranolazine multiple compressed tablets |
| CN110898024A (en) * | 2019-12-17 | 2020-03-24 | 卓和药业集团有限公司 | Pharmaceutical composition for treating angina pectoris and preparation method thereof |
| CN110882316A (en) * | 2019-12-23 | 2020-03-17 | 卓和药业集团有限公司 | Compound preparation of anti-angina pectoris medicine and preparation method thereof |
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Open date: 20100203 |