CN101584700A - A kind of pharmaceutical composition - Google Patents
A kind of pharmaceutical composition Download PDFInfo
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- CN101584700A CN101584700A CNA2009101580643A CN200910158064A CN101584700A CN 101584700 A CN101584700 A CN 101584700A CN A2009101580643 A CNA2009101580643 A CN A2009101580643A CN 200910158064 A CN200910158064 A CN 200910158064A CN 101584700 A CN101584700 A CN 101584700A
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- amlodipine
- hydrochlorothiazide
- pharmaceutical composition
- candesartan cilexetil
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Abstract
The invention belongs to technical field of Chinese medicines, a kind of pharmaceutical composition is specifically disclosed, the candesartan Cilexetil, hydrochlorothiazide and the amlodipine that wherein contain certain proportioning, Pharmaceutical composition of the present invention can be used for hypertension and medicine for treating diabetic nephropathy and use by the two mutual synergism.
Description
Technical field
The invention belongs to medical technical field, relate in particular to a kind of pharmaceutical composition and preparation method that contains candesartan Cilexetil, hydrochlorothiazide and amlodipine, and the purposes aspect hypertension and diabetic nephropathy.
Background technology
At present, hypertension and diabetic nephropathy have become the first cause that causes human death.The whole world has 1,600 ten thousand people to die from hypertension and diabetic nephropathy every year, accounts for more than 20% of general mortality rate.
Annual nearly more than 300 ten thousand people of China die from hypertension and diabetic nephropathy, because being the pathological changes because of blood, this disease causes, it is concealed, gradually to the infringement of human body, general, there is not tangible clinical symptoms, thereby be called as " reticent disease ", yet it but is first killer of human health.Suppressing the blood coagulation, improve blood fluidity, is one of key areas of cardiovascular medicament research and development.
Hypertension is modal cardiovascular diseases, is the great public health problem in the global range.Hypertension markization prevalence was 11.26% to 940,000 crowd's sample census more than 15 years old in 1991 in China, compared with 1979-1980, and prevalence increases by 25% in the period of 10.According to World Health Organization's prediction, to the year two thousand twenty, noninfectious will account for 79% of China's cause of death, and wherein the cardiovascular diseases will account for the first place.State-owned patient more than 100,000,000 at present, there are more than 5,000 ten thousand patients in the U.S..
Amlodipine (amlodipine) is the second filial generation 1,4 dihydropyridine type calcium antagonists that the mid-80 comes out, though its chemical constitution is similar to nifedipine (nifedipine), has unique pharmacological characteristics, and blood vessel, tissue are had more selectivity.Amlodipine is a dihydrogen pyridine derivatives, has the water solublity of height.On molecular structure with nifedipine have 2 different, promptly a chloride ion has replaced nitro, and it is amino to have an alkalescence on the dihydropyridine ring side chain, makes amlodipine be ionized form more than 90% when physiological PH value.Slowly and complete, 6～12h reaches the blood drug level peak value to this medicine oral absorption, and bioavailability is 60%～65%.Water preparation and tablet are not on an empty stomach all having influence to bioavailability with taking after the meal.Oral dose, blood drug level peak value (Cmax) and area under the concentration-time curve (AUC) are linear.Amlodipine distribution volume big (21L/Kg), plasma protein binding rate is 92%-98%.Reach stabilised blood concentration after taking 7 single agent continuously.
Similar and other calcium antagonist of amlodipine, the interior stream of Ca2+ that suppresses vascular smooth muscle cell, can also suppress the sympathetic nerve end and discharge norepinephrine slightly, blood plasma catechlolamine is descended, thereby cause the lax and expansion of small artery, it mainly acts on peripheral vessels, also expansible coronary artery and renal artery.This medicine and acceptor site effect take place slowly to make its blood vessel dilating effect steady, thereby greatly reduced and the relevant untoward reaction of the quick vasodilation of other antihypertensive drugs.Amlodipine does not all have the obvious suppression effect to conducting system of heart and myocardial contraction, can reduce cardiac load, reverses left ventricular hypertrophy, has report to think recently and can be used for heart failure patient safely.Amlodipine has no adverse effects to blood glucose, blood fat and serum electrolyte.Studies show that amlodipine can suppress the HDL-C expression of receptor, delays atherosclerosis, reduce the deposition of cholesterol, also can suppress platelet aggregation at arterial wall.
Candesartan Cilexetil is hydrolyzed into the active metabolite Candesartan in vivo rapidly, Candesartan is selectivity angiotensin-ii receptor (AT1) antagonist, vasoconstriction effect by the nervous plain II of antagonizing vessel with vascular smooth muscle AT1 receptors bind, thereby reduction peripheral vascular resistance. other has and thinks: Candesartan can be brought into play certain hypotensive effect by suppressing the acth secretion aldosterone. and Candesartan does not suppress kininase II, does not influence the Kallidin I degraded.
The test of carrying out the hyperpietic shows: but the patient repeatedly takes candesartan Cilexetil hyperamization slurry renin activity, and angiotensin I concentration and Angiotensin II concentration raise; This product 2-8mg every day, 1 continuous use can make systolic pressure, and diastolic pressure descends, left ventricular mass, and peripheral vascular resistance reduces, and to heart output, ejection fraction, renal vascular resistance, renal blood flow, glomerular filtration rate do not have obvious influence; To the primary hypertension patient of cerebrovascular disorders is arranged, cerebral blood flow there is not influence.
But incomplete, feed can increase absorbtivity to the hydrochlorothiazide oral absorption rapidly, may prolong relevant in the holdup time of small intestinal with medicine.This medicine part combines with plasma protein, and part enters in the erythrocyte in addition.Worked in oral 2 hours, peak time is 4 hours, and acting duration is 6～12 hours.T1/2 is 15 hours, and the impaired renal function person prolongs.This medicine absorbs the back and eliminates the blood drug level decline of phase incipient stage comparatively fast, and later blood drug level descends and obviously slows down, and may be because the after-stage medicine enters in the erythrocyte relevant.Mainly with original shape by homaluria.
Hydrochlorothiazide is adapted to edema disease, and congestive heart failure, cirrhotic ascites, the nephrotic syndrome, acute and chronic nephritis edema, chronic renal failure are early stage, sodium, water retention and hypertension due to adrenocortical hormone and the estrin treatment; The renal calculus that also can be used for central or nephrogenic diabetes insipidus prevention calcic salt component.
Summary of the invention
An object of the present invention is to disclose a kind of pharmaceutical composition.
Pharmaceutical composition of the present invention is made up of candesartan Cilexetil, hydrochlorothiazide and amlodipine, and wherein the weight ratio of candesartan Cilexetil, hydrochlorothiazide and amlodipine is 1-10: 2-15: 1-8.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 3-9: 5-15: 2-8.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 3-8: 5-15: 2-6.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4-6: 5-15: 2.5-5.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4-5: 5-10: 2.5-5.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4: 5-8: 2.5-5.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 5: 6.25: 2.5.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 8: 6.25: 2.5.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4: 6.25: 2.5.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4: 6.25: 5.
Above-mentioned pharmaceutical composition is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 8: 6.25: 5.
The application of above-mentioned pharmaceutical composition in preparation treatment hypertension or medicine for treating diabetic nephropathy.
The various dosage forms of pharmaceutical composition of the present invention can be according to the conventional production method preparation of pharmaceutical field.Such as using said composition to mix, be made into required dosage form then with one or more carriers.The selection of multiple dosage form helps the compliance of patient treatment, and the quality of life of improving patient has positive effect.
Candesartan Cilexetil of the present invention, hydrochlorothiazide and amlodipine adopt the raw material that meets medicinal standard, and hydrochlorothiazide of the present invention and amlodipine all calculate with the original shape medicine, and salifiable acid group does not calculate in weight portion.
The present invention also provides this preparation of drug combination method that contains hydrochlorothiazide and amlodipine.Weight portion of the present invention can be the known content units of field of medicaments such as μ g, mg, g, kg.
By a large amount of screening experiment, we are by candesartan Cilexetil and chemicals combined sorting anticoagulating active, find that pharmaceutical composition of the present invention can the significant prolongation clotting time, thereby hypertension and diabetic nephropathy are had therapeutical effect preferably.And found through experiments, the contained candesartan Cilexetil of the present invention does not have the effect of anticoagulating active separately, has anticoagulating active after the combination and significantly strengthens.This also is innovation of the present invention place.Find that by clinical verification it is outstanding to the curative effect of cardiovascular disease to invent described pharmaceutical composition, be better than using separately the therapeutic effect of hydrochlorothiazide and amlodipine or candesartan Cilexetil.
The specific embodiment
Further describe the present invention with embodiment below, help understanding, but described embodiment and experimental example only are used to illustrate the present invention rather than restriction the present invention the present invention and advantage thereof, better effects if." pharmaceutical composition that contains hydrochlorothiazide and amlodipine " is hereinafter to be referred as " pharmaceutical composition " among the present invention.
Experimental example 1
1 materials and methods
1.1 animal: Kunming mouse.
1.2 experimental drug: candesartan Cilexetil, hydrochlorothiazide and amlodipine, diosmin, dramedilol, citicoline, dibenzylchlorethamine, nisoldipine, diniprofylline, drobuline, drocarbil, drocinonide, dribendazole.
1.3 method
1.3.1 normal mouse is got in the normal mouse coagulation time test, male and female half and half, and (20 ± 2g), random packet is irritated stomach (ig) administration or isometric(al) distilled water, every day 1 time, continuous 4 days to body weight.After the last administration 1 hour, pluck eyeball and get blood, measure clotting time (CT) with capillary glass-tube method.
1.3.2 statistical method adopts the t check, data are represented with mean x ± s.
Table 1 candesartan Cilexetil and chemicals combination are to the The selection result of clotting time of mice
With matched group group ratio, * P＜0.05, * * P＜0.01
Table 2 candesartan Cilexetil and hydrochlorothiazide and amlodipine combination are to the The selection result of clotting time of mice
| Group | Dosage and part by weight | Clotting time (second) |
| Matched group | / | 125±29 |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (4: 6.25: 2.5) | 50 milligrams/kg body weight | 259±53* |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (3: 6.25: 2.5) | 50 milligrams/kg body weight | 235±33* |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (4: 6.25: 5) | 50 milligrams/kg body weight | 292±42** |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (2: 3: 12) | 50 milligrams/kg body weight | 257±39** |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (4: 5: 10) | 50 milligrams/kg body weight | 218±31* |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (4: 8: 8) | 50 milligrams/kg body weight | 258±56* |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (8: 10: 10) | 50 milligrams/kg body weight | 234±55* |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (4: 5: 12) | 50 milligrams/kg body weight | 308±36* |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (4: 8: 12) | 50 milligrams/kg body weight | 288±53* |
| Candesartan Cilexetil+hydrochlorothiazide and amlodipine (8: 6: 10) | 50 milligrams/kg body weight | 267±45* |
With matched group group ratio, * P＜0.05, * * P＜0.01
2 conclusions: table 1 experimental result shows, use candesartan Cilexetil or hydrochlorothiazide and amlodipine all not to have activity separately, and but candesartan Cilexetil and hydrochlorothiazide and amlodipine combination significant prolongation clotting time of mice shows that this pharmaceutical composition has to bring high blood pressure down.
Claims (12)
1. a pharmaceutical composition is characterized in that, described pharmaceutical composition is made up of candesartan Cilexetil, hydrochlorothiazide and amlodipine, and wherein the weight ratio of candesartan Cilexetil, hydrochlorothiazide and amlodipine is 1-10: 2-15: 1-8.
2. pharmaceutical composition according to claim 1 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 3-9: 5-15: 2-8.
3. pharmaceutical composition according to claim 2 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 3-8: 5-15: 2-6.
4. pharmaceutical composition according to claim 3 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4-6: 5-15: 2.5-5.
5. pharmaceutical composition according to claim 4 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4-5: 5-10: 2.5-5.
6. pharmaceutical composition according to claim 5 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4: 5-8: 2.5-5.
7. pharmaceutical composition according to claim 6 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 5: 6.25: 2.5.
8. pharmaceutical composition according to claim 6 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 8: 6.25: 2.5.
9. pharmaceutical composition according to claim 6 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4: 6.25: 2.5.
10. pharmaceutical composition according to claim 6 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 4: 6.25: 5.
11. pharmaceutical composition according to claim 6 is characterized in that, the weight ratio of wherein said candesartan Cilexetil, hydrochlorothiazide and amlodipine is 8: 6.25: 5.
12. the application of the described pharmaceutical composition of claim 1-11 in preparation anticoagulation and hypertension drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CNA2009101580643A CN101584700A (en) | 2009-07-20 | 2009-07-20 | A kind of pharmaceutical composition |
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| CNA2009101580643A CN101584700A (en) | 2009-07-20 | 2009-07-20 | A kind of pharmaceutical composition |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101972253A (en) * | 2010-09-06 | 2011-02-16 | 海南美兰史克制药有限公司 | Candesartan ester amlodipine besylate pharmaceutical composition lipid microsphere tablet |
| CN102342942A (en) * | 2011-07-14 | 2012-02-08 | 海南锦瑞制药股份有限公司 | Novel oral solid medicinal composition and preparation method thereof |
| CN104857025A (en) * | 2015-05-28 | 2015-08-26 | 徐忠兰 | Therapeutic method by utilizing medicines to cure diabetics |
| WO2017054787A1 (en) * | 2015-10-02 | 2017-04-06 | Zentiva, K.S. | Pharmaceutical composition comprising the combination of candesartan, amlodipine and hydrochlorothiazide |
| EP3219309A1 (en) * | 2016-03-17 | 2017-09-20 | K.H.S. Pharma Holding GmbH | Fixed dosed pharmaceutical composition comprising amlodipine, candesartan cilexetil and hydrochlorothiazide for the treatment of hypertension |
| WO2023285646A1 (en) | 2021-07-15 | 2023-01-19 | Adamed Pharma S.A | A pharmaceutical composition comprising amlodipine, candesartan cilexetil and hydrochlorothiazide for the treatment of hypertension |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450211A (en) * | 2007-12-07 | 2009-06-10 | 上海艾力斯医药科技有限公司 | Composite antihypertensive preparation |
-
2009
- 2009-07-20 CN CNA2009101580643A patent/CN101584700A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450211A (en) * | 2007-12-07 | 2009-06-10 | 上海艾力斯医药科技有限公司 | Composite antihypertensive preparation |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101972253A (en) * | 2010-09-06 | 2011-02-16 | 海南美兰史克制药有限公司 | Candesartan ester amlodipine besylate pharmaceutical composition lipid microsphere tablet |
| CN102342942A (en) * | 2011-07-14 | 2012-02-08 | 海南锦瑞制药股份有限公司 | Novel oral solid medicinal composition and preparation method thereof |
| CN102342942B (en) * | 2011-07-14 | 2016-08-31 | 海南锦瑞制药有限公司 | A kind of New oral solid medicinal compositions and preparation method thereof |
| CN104857025A (en) * | 2015-05-28 | 2015-08-26 | 徐忠兰 | Therapeutic method by utilizing medicines to cure diabetics |
| WO2017054787A1 (en) * | 2015-10-02 | 2017-04-06 | Zentiva, K.S. | Pharmaceutical composition comprising the combination of candesartan, amlodipine and hydrochlorothiazide |
| EP3219309A1 (en) * | 2016-03-17 | 2017-09-20 | K.H.S. Pharma Holding GmbH | Fixed dosed pharmaceutical composition comprising amlodipine, candesartan cilexetil and hydrochlorothiazide for the treatment of hypertension |
| WO2017158094A1 (en) * | 2016-03-17 | 2017-09-21 | K.H.S. Pharma Holding Gmbh | Fixed dosed pharmaceutical composition comprising amiodipine, candesartan cilexetil and hydrochlorothiazide for the treatment of hypertension. |
| CN109069432A (en) * | 2016-03-17 | 2018-12-21 | 德国麦德斯医药有限公司 | For treating the fixed dose medication composition comprising Amlodipine, Candesartan Cilexetil and Hydrochioro of hypertension |
| WO2023285646A1 (en) | 2021-07-15 | 2023-01-19 | Adamed Pharma S.A | A pharmaceutical composition comprising amlodipine, candesartan cilexetil and hydrochlorothiazide for the treatment of hypertension |
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Application publication date: 20091125 |