CN102247344A - Novel blood pressure reducing composition - Google Patents
Novel blood pressure reducing composition Download PDFInfo
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- CN102247344A CN102247344A CN2011101418478A CN201110141847A CN102247344A CN 102247344 A CN102247344 A CN 102247344A CN 2011101418478 A CN2011101418478 A CN 2011101418478A CN 201110141847 A CN201110141847 A CN 201110141847A CN 102247344 A CN102247344 A CN 102247344A
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Abstract
The invention relates to a novel blood pressure reducing composition. The blood pressure reducing composition is a medicinal composition of which active ingredients are any one or two of aliskiren and a medicinal salt thereof, a hydrate, a calcium channel blocker (CCB), an angiotensin type 1 (AT1) receptor blocker (ARB), an angiotensin-converting enzyme inhibitor (ACEI), hydrochlorothiazide and the like. The composition can be prepared into oral tablets or capsules and is used for treating hypertension, and the curative effect is superior to the blood pressure reducing effect of the independent aliskiren.
Description
Technical field
The present invention is a kind of novel blood pressure lowering compositions, belongs to medical technical field.
Background technology
Hypertension is the popular cardiovascular disease the most widely in the world today, it is again the important risk that causes coronary heart disease, apoplexy and renal failure, the hyperpietic not only has blood pressure to increase with hemodynamic unusual, and, belong to a kind of systemic disease often with the infringement of target organs such as sugar, lipid metabolic disorder and the heart, brain, kidney.Antihypertensive drug is more clinically, comprises diuretic, beta-Blocking agent, angiotensin converting enzyme inhibitor (ACE-I), Angiotensin II (AT II) receptor antagonist, calcium antagonist and α-Zu Zhiji.But they all have its certain limitation and side effect in the use.So side effect is little, better tolerance, and the antihypertensive of stable curative effect will be widely used as an ideal line depressor, and wherein stable curative effect, the little compound hypertension medicine of side effect also have been subjected to paying close attention to widely.
Aliskiren is a second filial generation renin inhibitor, acts on first rate-limiting step of renin-angiotensin-aldosterone system (RAS).All research datas all show at present, and aliskiren blood pressure lowering treatment has good safety and effectiveness, few side effects, long half time, taking convenience once a day.Aliskiren is the oral renin inhibitor of first kind of treatment hypertension and other cardiovascular disease and nephropathy.Aliskiren can effectively reduce light moderate hypertension patient's blood pressure level.And do not produce reflex tachycardia, do not influence cardiac function; Hypotensive effect is the feritin dependency, and therefore heavy dose of administration only can prolong action time, can not cause the blood pressure rapid drawdown.
Summary of the invention
The present invention is a kind of new blood pressure lowering compositions, it is characterized in that: be to be the Pharmaceutical composition of active component with aliskiren and pharmaceutical salts, hydrate and any 1-2 kind material as described below:
Material 1: calcium ion antagonist (CCB) comprises nifedipine, amlodipine, lercanidipine, felodipine, nilvadipine, lacidipine, nisoldipine and their pharmaceutical salts, optical isomer and hydrate;
Material 2:AT1 receptor antagonist (ARB) comprises valsartan, candesartan Cilexetil, olmesartan medoxomil, irbesartan, losartan, telmisartan, Eprosartan and their pharmaceutical salts, optical isomer and hydrate etc.;
Material 3: angiotensin converting enzyme inhibitor (ACEI) comprises captopril, lisinopril, ramipril, fosinopril, enalapril, benazepril, delapril and their pharmaceutical salts, optical isomer and hydrate etc.;
Material 4: hydrochlorothiazide
The preferred fumarate of the pharmaceutical salts of aliskiren.The pharmaceutical salts of calcium ion antagonist comprises hydrochlorate, mesylate, benzene sulfonate, maleate etc.
Preferred composition of the present invention is: aliskiren+Levamlodipine Besylate; Aliskiren+Levamlodipine Besylate+hydrochlorothiazide; Aliskiren+Levamlodipine Besylate+valsartan; Aliskiren+captopril, aliskiren+hydrochlorothiazide+captopril etc.;
The unit consumption of aliskiren is 37.5-1200mg, and preferred dose is 150-300mg;
The unit consumption of hydrochlorothiazide is 5-200mg, and preferred dose is 25-50mg;
The unit consumption of calcium ion antagonist (CCB) is: the unit consumption of (left side) amlodipine is 1.25-40mg, and preferred dose is 5-10mg; The unit consumption of nifedipine is 1.25-40mg, is preferably 5-10mg; The unit consumption of lercanidipine is 2.5-80mg, is preferably 10-20mg; The unit consumption of felodipine is 2.5-80mg, is preferably 10-20mg; The unit consumption of nilvadipine is 0.5-16mg, is preferably 2-4mg; The unit consumption of lacidipine is 1-24mg, is preferably 4-6mg;
The unit consumption of Manidipine is 1.25-40mg, is preferably 5-10mg.
The unit consumption of AT1 receptor antagonist (ARB) is: the unit consumption of olmesartan medoxomil is 5-160mg, is preferably 10-80mg;
The unit consumption of irbesartan is 37.5-600mg, is preferably 75-300mg; The unit consumption of candesartan Cilexetil is 1-32mg, is preferably 2-16mg; The unit consumption of Losartan Potassium is 12.5-200mg, is preferably 25-100mg; The unit consumption of telmisartan is 10-320mg, is preferably 20-160mg; The unit consumption of valsartan is 20-320mg, is preferably 40-160mg; The unit consumption of Eprosartan is 100-1200mg, is preferably 200-600mg.
The unit consumption of angiotensin converting enzyme inhibitor (ACEI) is: the unit consumption of captopril is 6.25-100mg, is preferably 12.5-50mg.The unit consumption of lisinopril is 5-80mg, is preferably 10-40mgmg; The unit consumption of ramipril is 0.5-20mg, is preferably 1.25-10mg; The unit consumption of fosinopril is 5-80mg, is preferably 10-40mg; The unit consumption of enalapril is 1.25-40mg, is preferably 2.5-20mg; The unit consumption of benazepril is 5-80mg, is preferably 10-40mg; 7 consumptions of the list of delapril are 15-120mg, are preferably 7.5-60mg.
Pharmaceutical composition of the present invention can be made into oral formulations, comprises granule, ordinary tablet, chewable tablet, dispersible tablet, oral cavity disintegration tablet, buccal tablet, capsule, soft capsule, drop pill, slow releasing tablet, slow releasing capsule etc.
The specific embodiment
Embodiment 1: tablet
| The supplementary material title | 1 | 2 | 3 | 4 | 5 |
| The fumaric acid aliskiren | 150g | 150g | 150g | 150g | 150g |
| The left-handed chlorine Flordipine of benzenesulfonic acid | 5g | 7.5g | 10g | ---- | ---- |
| Hydrochlorothiazide | ---- | 25g | ---- | ---- | 25g |
| Valsartan | ---- | ---- | 40g | ---- | ---- |
| Captopril | ---- | ---- | ---- | 25g | 12.5g |
| Microcrystalline Cellulose | 85g | 80g | 45g | 65g | 75g |
| Lactose | 36g | 36g | 36g | 36g | 36g |
| Sodium carboxymethyl cellulose | 10g | 10g | 10g | 10g | 10g |
| Pregelatinized Starch | 55g | 55g | 55g | 55g | 55g |
| Magnesium stearate | 1.6g | 1.6g | 1.6g | 1.6g | 1.6g |
| Purified water | In right amount | In right amount | In right amount | In right amount | In right amount |
Annotate: fumaric acid aliskiren specification is in aliskiren, and Levamlodipine besylate is in amlodipine
Technology: get each crude drug, morcelled 100 mesh sieves respectively, standby; Each adjuvant is crossed 60 mesh sieves respectively, and is standby; Except that magnesium stearate, get each supplementary material respectively, put mix homogeneously in the high-speed mixing granulating machine, add suitable quantity of water system soft material, 24 orders are granulated, 50 degree fluid bed dryings, 24 order granulate add magnesium stearate, mix homogeneously, tabletting carries out coating promptly to this plain sheet.
Embodiment 2: chewable tablet
| The supplementary material title | 1 | 2 | 3 | 4 | 5 |
| The fumaric acid aliskiren | 150g | 150g | 150g | 150g | 150g |
| The left-handed chlorine Flordipine of benzenesulfonic acid | 5g | 7.5g | 10g | ---- | ---- |
| Hydrochlorothiazide | ---- | 25g | ---- | ---- | 25g |
| Valsartan | ---- | ---- | 40g | ---- | ---- |
| Captopril | ---- | ---- | ---- | 25g | 12.5g |
| Mannitol | 205g | 195g | 160g | 185g | 175g |
| Sorbitol | 105g | 105g | 105g | 105g | 105g |
| Sodium carboxymethyl cellulose | 10g | 10g | 10g | 10g | 10g |
| Sucralose | 5g | 5g | 5g | 5g | 5g |
| Essence | In right amount | In right amount | In right amount | In right amount | In right amount |
| Magnesium stearate | 1.6g | 1.6g | 1.6g | 1.6g | 1.6g |
| Purified water | In right amount | In right amount | In right amount | In right amount | In right amount |
Annotate: fumaric acid aliskiren specification is in aliskiren, and Levamlodipine besylate is in amlodipine
Technology: get each supplementary material medicine, morcelled 100 mesh sieves respectively, standby; Except that magnesium stearate, get each supplementary material respectively, put mix homogeneously in the high-speed mixing granulating machine, add suitable quantity of water system soft material, 24 orders are granulated, 50 degree fluid bed dryings, 24 order granulate add magnesium stearate, mix homogeneously, tabletting, promptly.
Embodiment 3 curative effect confirmatory experiments
Below be the therapeutic evaluation experiment, further specify the curative effect advantage of the present composition.
1. experimental technique:
Get 110 of healthy male SD rats, after adaptability fed for 1 week. survey basic blood pressure with RBP-1 rat blood pressure instrument.Art fasting evening before yesterday 12h, inferior modeling in morning.All blood pressures is than before handling more than the high 2.66kPa (greater than 3 standard differences of normal arterial pressure) behind the modeling 4w, and is higher than 15.30kPa person and is defined as the high blood pressure disease model and forms.The rat of modeling success is divided at random: aliskiren (A), Levamlodipine Besylate (B1), aliskiren+Levamlodipine Besylate (B2); Aliskiren+Levamlodipine Besylate+hydrochlorothiazide (B3), olmesartan medoxomil (C1), aliskiren+olmesartan medoxomil (C2), aliskiren+olmesartan medoxomil+hydrochlorothiazide (C3), captopril (D1), aliskiren+captopril (D2), aliskiren+captopril+hydrochlorothiazide (D3), blank model group (O), other gets 10 of healthy SD rats, establishes the blank group.Matched group and blank model group are irritated stomach with 1ml/100g body weight normal saline, irritate stomach for all the other 3 groups and give relative medicine, and all with the normal saline preparation, irritate the stomach volume is the 1ml/100g body weight to medicine, 4 weeks of successive administration.In dry, ventilation, quiet environment.After the preheating of RBP-1 rat blood pressure instrument, rat is put in the heated at constant temperature case behind preheating 10～15min, measure systolic pressure, heart rate, each time point is surveyed 3 times, gets mean.Blood pressure, heart rate measurement carry out at following time point: the 1st, 2,3,4 weekends after the 4th weekend, the administration before the operation, after the operation.Blood pressure determination after the administration should begin to carry out by 2h after administration.
2. statistical procedures: adopt SPSS software to carry out statistical analysis, experimental result all uses first x ± s to represent, organizes mean more and relatively adopts the ANOVA variance analysis, relatively checks with q between group.There is the significance meaning P≤0.05 for difference.
3 results
4 weeks of postoperative compare with blank model group, and each administration group all has tangible antihypertensive effect, and with respect to aliskiren folk prescription administration group, compound recipe administration group hypotensive effect is remarkable, irritate stomach after 1 week, and blood pressure begins to drop to successive administration 4 weekends (P＜0.05).See Table 1.
The influence of table 1 pair renal hypertensive rat blood pressure
Claims (10)
1. new blood pressure lowering compositions is characterized in that: be to be the Pharmaceutical composition of active component with aliskiren and pharmaceutical salts, hydrate and any 1-2 kind material as described below:
Material 1: calcium ion antagonist (CCB) comprises nifedipine, amlodipine, lercanidipine, felodipine, nilvadipine, lacidipine, nisoldipine and their pharmaceutical salts, optical isomer and hydrate;
Material 2:AT1 receptor antagonist (ARB) comprises valsartan, candesartan Cilexetil, olmesartan medoxomil, irbesartan, losartan, telmisartan, Eprosartan and their pharmaceutical salts, optical isomer and hydrate etc.;
Material 3: angiotensin converting enzyme inhibitor (ACEI) comprises captopril, lisinopril, ramipril, fosinopril, enalapril, benazepril, delapril and their pharmaceutical salts, optical isomer and hydrate etc.;
Material 4: hydrochlorothiazide.
2. the described Pharmaceutical composition of claim 1 is characterized in that, the pharmaceutical salts of aliskiren is a fumarate.
3. the described Pharmaceutical composition of claim 1 is characterized in that the pharmaceutical salts of calcium ion antagonist comprises hydrochlorate, mesylate, benzene sulfonate, maleate.
4. the described Pharmaceutical composition of claim 1, it is characterized in that: compositions is: aliskiren+Levamlodipine Besylate; Aliskiren+Levamlodipine Besylate+hydrochlorothiazide; Aliskiren+Levamlodipine Besylate+valsartan; Aliskiren+captopril,
Aliskiren+hydrochlorothiazide+captopril.
5. the described Pharmaceutical composition of claim 1, it is characterized in that: the unit consumption of aliskiren is 37.5-1200mg, preferred dose is 150-300mg.
6. the described Pharmaceutical composition of claim 1 is characterized in that: the unit consumption of calcium ion antagonist (CCB) is,
The unit consumption of Levamlodipine Besylate is 1.25-40mg, and preferred dose is 5-10mg;
The unit consumption of nifedipine is 1.25-40mg, is preferably 5-10mg;
The unit consumption of lercanidipine is 2.5-80mg, is preferably 10-20mg;
The unit consumption of felodipine is 2.5-80mg, is preferably 10-20mg;
The unit consumption of nilvadipine is 0.5-16mg, is preferably 2-4mg;
The unit consumption of lacidipine is 1-24mg, is preferably 4-6mg;
The unit consumption of Manidipine is 1.25-40mg, is preferably 5-10mg.
7. the described Pharmaceutical composition of claim 1, it is characterized in that: the unit consumption of AT1 receptor antagonist (ARB) is:
The unit consumption of olmesartan medoxomil is 5-160mg, is preferably 10-80mg;
The unit consumption of irbesartan is 37.5-600mg, is preferably 75-300mg;
The unit consumption of candesartan Cilexetil is 1-32mg, is preferably 2-16mg;
The unit consumption of Losartan Potassium is 12.5-200mg, is preferably 25-100mg;
The unit consumption of telmisartan is 10-320mg, is preferably 20-160mg;
The unit consumption of valsartan is 20-320mg, is preferably 40-160mg;
The unit consumption of Eprosartan is 100-1200mg, is preferably 200-600mg.
8. the described Pharmaceutical composition of claim 1, it is characterized in that: the unit consumption of angiotensin converting enzyme inhibitor (ACEI) is:
The unit consumption of captopril is 6.25-100mg, is preferably 12.5-50mg;
The unit consumption of lisinopril is 5-80mg, is preferably 10-40mgmg;
The unit consumption of ramipril is 0.5-20mg, is preferably 1.25-10mg;
The unit consumption of fosinopril is 5-80mg, is preferably 10-40mg;
The unit consumption of enalapril is 1.25-40mg, is preferably 2.5-20mg;
The unit consumption of benazepril is 5-80mg, is preferably 10-40mg;
The unit consumption of delapril is 15-120mg, is preferably 7.5-60mg.
9. the described Pharmaceutical composition of claim 1, it is characterized in that: the unit consumption of hydrochlorothiazide is 5-200mg, preferred dose is 25-50mg.
10. the described Pharmaceutical composition of claim 1 is characterized in that: can be made into oral formulations, comprise granule, tablet, capsule, drop pill.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102430109A (en) * | 2011-12-02 | 2012-05-02 | 邬林祥 | Amlodipine, aliskiren and pril compound antihypertensive medicament |
| CN102552911A (en) * | 2011-12-02 | 2012-07-11 | 邬林祥 | Levoamlodipine, aliskiren and sartan compound antihypertensive medicine |
| CN102552873A (en) * | 2011-12-02 | 2012-07-11 | 邬林祥 | Levoamlodipine, aliskiren and pril compound antihypertensive medicine |
| CN102552255A (en) * | 2011-12-02 | 2012-07-11 | 邬林祥 | Amlodipine, aliskiren and sartan compound antihypertensive medicine |
| CN102552276A (en) * | 2011-12-02 | 2012-07-11 | 邬林祥 | Levoamlodipine, aliskiren and hydrochlorothiazide compound antihypertensive medicine |
| CN107029208A (en) * | 2017-06-13 | 2017-08-11 | 江苏黄河药业股份有限公司 | It is a kind of to treat lisinopril compound preparation of angiocardiopathy and preparation method thereof |
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| CN101926793A (en) * | 2010-08-05 | 2010-12-29 | 成都自豪药业有限公司 | Combined medicament containing telmisartan and aliskiren and preparation method thereof |
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| CN101990428A (en) * | 2008-04-10 | 2011-03-23 | 韩兀生物制药株式会社 | Pharmaceutical formulation |
| WO2010033954A2 (en) * | 2008-09-22 | 2010-03-25 | Novartis Ag | Galenical formulations of organic compounds |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102430109A (en) * | 2011-12-02 | 2012-05-02 | 邬林祥 | Amlodipine, aliskiren and pril compound antihypertensive medicament |
| CN102552911A (en) * | 2011-12-02 | 2012-07-11 | 邬林祥 | Levoamlodipine, aliskiren and sartan compound antihypertensive medicine |
| CN102552873A (en) * | 2011-12-02 | 2012-07-11 | 邬林祥 | Levoamlodipine, aliskiren and pril compound antihypertensive medicine |
| CN102552255A (en) * | 2011-12-02 | 2012-07-11 | 邬林祥 | Amlodipine, aliskiren and sartan compound antihypertensive medicine |
| CN102552276A (en) * | 2011-12-02 | 2012-07-11 | 邬林祥 | Levoamlodipine, aliskiren and hydrochlorothiazide compound antihypertensive medicine |
| CN107029208A (en) * | 2017-06-13 | 2017-08-11 | 江苏黄河药业股份有限公司 | It is a kind of to treat lisinopril compound preparation of angiocardiopathy and preparation method thereof |
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Application publication date: 20111123 |