CN100374113C - Hypotensor composition - Google Patents
Hypotensor composition Download PDFInfo
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- CN100374113C CN100374113C CNB2006100444031A CN200610044403A CN100374113C CN 100374113 C CN100374113 C CN 100374113C CN B2006100444031 A CNB2006100444031 A CN B2006100444031A CN 200610044403 A CN200610044403 A CN 200610044403A CN 100374113 C CN100374113 C CN 100374113C
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Abstract
The present invention belongs to the field of medicine, which particularly relates to medicine for reducing blood pressure. Effective components of the present invention comprise nitrendipine and prazosin hydrochloride or hydrochlorothiazide, auxiliary materials comprise starch, sugar powder, dextrin, magnesium stearate, talcum powder, etc., the effective components and the auxiliary materials are prepared into two kinds of compound tablets for reducing blood pressure, and the tablets are taken cooperatively according to specific conditions. The medicine has mild and lasting effects and less side effects, patients feel comfortable in the process of controlling blood pressure, and the medicine has particularly obvious curative effects on moderate hypertension and serious hypertension.
Description
Technical field
The invention belongs to field of medicaments, relate in particular to a kind of hypotensor composition.
Background technology
Hypertension is old high morbidity, disability rate and case fatality rate height, and the viewpoint of present international hypertension alliance is, as long as patient can tolerate, reduces to normal level as far as possible, thinks that also the low dose of dehydrated pharmaceutical of prolonged application is safe and effective.Clinical have the control of multiclass medicine, but the single medicine effect is relatively poor, and drug side effect is more.
Nitrendipine is a second filial generation dihydropyridine calcium channel antagonist, and the effect of obvious expansion peripheral blood vessel is arranged, and is applicable to each phase hypertension, but list is used weak effect, easily produces drug resistance.
Minipress is the alpha 1-receptor inhibitor, also can stop peripheral venous and vein postsynaptic membrane alpha 1-receptor by selectivity, it does not influence alpha-2 receptor, distend the blood vessels, not causing during blood pressure lowering tachycardia does not influence renal function, blood fat and blood glucose do not raise, be applicable to light middle hypertension or kidney type hypertension, list is used weak effect, also easily produces drug resistance.
Summary of the invention
In order to overcome the shortcoming that prior art exists, the invention provides a kind of hypotensor composition.
A kind of hypotensor composition, by weight, active ingredient is made up of for 25 parts 20 parts of nitrendipines, 2 parts of minipresses, hydrochlorothiazide; Adjuvant is by 136 parts of starch, 72 parts of Icing Sugar, 36 parts in dextrin, 3 parts of magnesium stearate, 6 parts of compositions of Pulvis Talci.
As compositions A, in order to strengthen result of use, said composition A can be used with compositions B with the medicine of said ratio, and its compositions B proportioning is as follows:
Hypotensor composition B, by weight, active ingredient is made up of 20 parts of nitrendipines, 2 parts of minipresses and adjuvant thereof; Adjuvant is by 99 parts of starch, 48 parts of Icing Sugar, 25 parts in dextrin, 2 parts of magnesium stearate, 4 parts of compositions of Pulvis Talci.
The manufacture method of hypotensor composition A is as follows:
(1) granulates: take by weighing active ingredient nitrendipine, minipress, hydrochlorothiazide by required parts by weight, reach supplementary product starch, Icing Sugar, dextrin mix homogeneously.Iron alkane ketone alcoholic solution with 5% polyethylene pyrrole and be made into soft material, reach " hold agglomerating, thrum easily looses ", granulate with oscillating granulator then by the pharmaceutical standards soft material.The preparation method that above-mentioned 5% polyethylene pyrrole irons alkane ketone alcoholic solution irons alkane ketone for taking by weighing 5 gram polyethylene pyrroles, be dissolved in 100 milliliters the dehydrated alcohol, cause wherein 5% polyethylene pyrrole irons all evaporations in drying course of alkane ketone alcoholic solution, so its weight can be ignored.Icing Sugar is that sucrose is pulverized the back and crossed the fine powder that 100 mesh sieves obtain, and the purpose that adds it is a particulate compressibility when increasing tabletting.
(2) oven dry: granule is dried down at 100 ℃.
(3) granulate: after the drying, use the pelletizing machine granulate.
(4) mix tabletting: add magnesium stearate and Pulvis Talci, behind the mixing, be pressed into the tablet of every 100mg～150mg with drift.
Below be minipress, Hydrochlorothiazide is made compound preparation prescription foundation:
One, monosomic analysis
By analyzing monomeric chemical constitution, draw in compound preparation, between nitrendipine, minipress, the hydrochlorothiazide chemical reaction can not take place, structure can not change.
Nitrendipine is 2,6-dimethyl-4-(3-nitrobenzophenone)-1,4-dihydro-3,5 pyridinedicarboxylic acid methyl ethyl ester.
Molecular formula: C18H20N206
Molecular weight: 360.37
Press dry product and calculate, contain C18H20N206 and must not be less than 99.0%.
Character: this product is yellow crystal or crystalline powder; Odorless, tasteless; Chance light is perishable.
This product is easily molten in acetone or chloroform, and is molten at methanol or ethanol part omitted, almost insoluble in water.
Fusing point: the fusing point of this product is 156～159 ℃.This product absorbs good, protein binding rate 98%, the half-life is 2 hours, more the apparatus sensitive mensuration half-life is 10-20 hour in the recent period, this product oral absorption is good, oral back 30 minutes systolic pressures begin to descend, and 60 minutes diastolic pressures begin to descend, and hypotensive effect was 1-2 hour maximum, continue 6-8 hour, this product is at liver metabolism, and its metabolite 70% is through renal excretion, and 8% discharges through excrement.
Minipress is 1-(4-amino-6,7-dimethoxy-2-quinazolyl)-4-(2-furoyl) piperazine hydrochloride.
Molecular formula: C19H21N504.HCl
Molecular weight: 419.87
Press dry product and calculate, contain C19H21N504HCl and must not be less than 98.0%.
Character: this product is white or off-white color crystalline powder; Odorless, tasteless.
This product is slightly soluble in ethanol, and is almost insoluble in water.This product absorbs fully, bioavailability 50%-80%, and protein binding rate 97%, 2 hours blood pressures begin to descend after this product oral absorption, and peak reaching time of blood concentration is 1-3 hour, half-life 2-3 hour, continuous action 10 hours.This product mainly by demethylation and covalent bonds form at the liver intracellular metabolite, with feces and bile excretion, only account for 6%-10% in the urine, 5%-11% discharges with original shape; During heart failure, clearance rate can not be removed by dialysis than normally being slow.
Hydrochlorothiazide is a 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide.
Molecular formula: C7H8ClN304S2
Molecular weight: 297.74
Press dry product and calculate, contain C7H8ClN304S2 and should be 98.5%～101.5%.
Character: this product is a white crystalline powder; Odorless, mildly bitter flavor.
This product is dissolved in acetone, and slightly soluble in ethanol is insoluble in water, chloroform or ether; In sodium hydroxide solution, dissolve.
Fusing point: the fusing point of this product is 265～273 ℃, decomposes simultaneously during fusion.
This medicine acts on medullary loop and rises the absorption again that branch thick section cortex portion (Distal convoluted tubule begins the position) suppresses NaCL, this section Na
+Amount reaches crude urine Na
+10%～15%, remove in the urine and contain more Cl-and Na
+Also contain K+ outward.This medicine oral absorption is good, and bioavailability is about 70%, and big Vd is arranged, and the half-life is 8-10 hour, in vivo not by metabolism, mainly by renal excretion, on a small quantity by bile excretion, can pass through Placenta Hominis.
By above monosomic analysis, each monomer is stable structure, chemical reaction can not take place each other, between do not have reciprocal influence, the condition of chemical compound generation chemical reaction does not satisfy, therefore, the compound preparation prescription is scientific and reasonable.
Two, the analysis between compound preparation and the adjuvant
Add during film-making with the order of adjuvant be to guarantee the disintegrative etc. of flowability, lubricity, compressibility and the finished product thereof of blood pressure lowering material.Adjuvant select for use improper or consumption uncomfortable, not only may influence the film-making process, and the performance of quality, stability and the curative effect thereof of tablet is had certain even material impact.Additive of tablet must have higher physics and chemical stability, does not react with principal agent and other adjuvants, does not influence release, absorption and the assay of principal agent, and is harmless, and cheap and easy to get.
Disintegrating agent of the present invention adopts starch, is applicable to tablet insoluble or the microsolubility medicine, with preceding 100 ℃ of dry 1h; Dry adhesive adopts dextrin, mainly makes the powder surface bonding; Lubricant adopts magnesium stearate and Pulvis Talci helps fluidity, block resistance is good.
Use nitrendipine by analysis and research, minipress, Hydrochlorothiazide is made compound preparation, chemical reaction can not take place, and structure can not change.When in the preparation process, making stones such as wetting agent and binding agent, disintegrating agent and lubricant, all not with stone generation chemical reaction, structure also can not change, for the compound preparation prescription provides theoretical foundation.From between pharmacological action, incompatibility, compound preparation and the stone, all there is reasonability in multiplicity such as clinical practice, the drug combination effect is obvious, overcome single nitrendipine, minipress and Hydrochlorothiazide medicine used, but had weak effect, shortcomings such as easy drug resistance.
The instructions of taking of pharmaceutical composition of the present invention: take Altace Ramipril B half sheet first before sleep, when blood pressure during in higher level, m seq is taken Altace Ramipril A a slice, takes Altace Ramipril B half sheet afternoon later on; When blood pressure during in higher level, m seq is taken Altace Ramipril A a slice, respectively takes Altace Ramipril B half sheet in noon and afternoon; When the still difficult control of blood pressure, m seq is taken Altace Ramipril A a slice, respectively takes Altace Ramipril B a slice in noon and afternoon.
Clinical effectiveness
Treat 60 routine patients, the hypertensive patient belongs to hypertension II phase and III phase through preliminary analysis.To 2 grades of hypertension (160～179/100～109mmHg), before sleep, take Altace Ramipril B half sheet first, m seq is taken Altace Ramipril A a slice, respectively takes Altace Ramipril B half sheet in noon and afternoon.When blood pressure is reduced to normal level, change Altace Ramipril B half sheet in afternoon into.
To 3 grades of hypertension (〉=180/110mmHg), before sleep, take Altace Ramipril B half sheet first, m seq is taken Altace Ramipril A a slice, respectively takes Altace Ramipril B a slice in noon and afternoon.When blood pressure is reduced to normal level, change in noon and afternoon and take Altace Ramipril B half sheet.
Measure one weekly to the secondary blood pressure, be 6 months the course of treatment the shortest, the longest 48 months, measures the blood pressure secondary every day, as contrast before and after the treatment.Blood pressure before and after the treatment, each former and later three mediodespidine average as a comparison.
60 routine patients, male's 35 examples, women's 25 examples, the oldest 70 years old, minimum 42 years old of age.Most of patient's reflections, sx is comparatively obvious, and liver, renal function and hemopoietic system are not all found harmful effect.
Criterion of therapeutical effect
Standard determination by national cardiovascular meeting formulation in 1964:
Significant curative effect means that (1) the back diastolic pressure of taking medicine reduces more than 20 millimetress of mercury, and reduces to normal range; (2) diastolic pressure reduces more than 30 millimetress of mercury.
Mean that effectively (1) diastolic pressure reduces to normal range, the decline actual number is the 10-19 millimetres of mercury; (2) diastolic pressure decline 10-19 millimetres of mercury, but do not reduce to normal range, and systolic pressure descends more than 30 millimetress of mercury; (3) diastolic pressure decline 20-29 millimetres of mercury, but do not reduce to normal range.
The invalid blood pressure drops that means does not reach above-mentioned every standard person.
The result
In 60 routine patients, significant curative effect 52 people account for 86.6%; Effective 7 people account for 11.7%; Invalid 1 people accounts for 1.7%; Total effective rate is 98.3%, illustrates that this medicine has sure antihypertensive effect.
III phase hyperpietic's medication shows, total effective rate is 96.5%, and wherein produce effects accounts for 88.6%, effectively accounts for 7.9%, illustrate that the present invention is not only effective to II phase hypertension, and the III phase patient who is combined the obvious heart, brain, the depletion of kidney device also there is excellent curative.Definite effect of the present invention, action temperature and, lasting, side effect is slight.In the controlling blood pressure process, patient's subjective sensation is comfortable, and centering, heavy hypertension curative effect are particularly suitable.
The specific embodiment
Now the specific embodiment of the present invention is described with embodiment.
Embodiment 1
A kind of hypotensor composition A, active ingredient is made up of for 25 kilograms 20 kilograms of nitrendipines, 2 kilograms of minipresses, hydrochlorothiazide by weight; Adjuvant contains 136 kilograms of starch, 72 kilograms of Icing Sugar, 36 kilograms in dextrin, 3 kilograms of magnesium stearate, 6 kilograms of Pulvis Talci.
The manufacture method of compositions A is as follows:
(1) granulates: take by weighing active ingredient nitrendipine, minipress, hydrochlorothiazide, starch, Icing Sugar, dextrin mix homogeneously by required parts by weight.Iron alkane ketone alcoholic solution with 5% polyethylene pyrrole and be made into soft material, granulate with oscillating granulator.The preparation method that above-mentioned 5% polyethylene pyrrole irons alkane ketone alcoholic solution irons alkane ketone for taking by weighing 5 gram polyethylene pyrroles, be dissolved in 100 milliliters the dehydrated alcohol, cause wherein 5% polyethylene pyrrole irons all evaporations in drying course of alkane ketone alcoholic solution, so its weight can be ignored.Icing Sugar is that sucrose is pulverized the back and crossed the fine powder that 100 mesh sieves obtain, and the purpose that adds it is a particulate compressibility when increasing tabletting.
(2) oven dry: granule is dried down at 100 ℃.
(3) granulate: after the drying, use the pelletizing machine granulate.
(4) mix tabletting: adding magnesium stearate and Pulvis Talci then, behind the mixing, is the tablet that 7 millimeters No. 7 drift tablettings are made every 150mg with diameter.
Embodiment 2
A kind of hypotensor composition B, active ingredient is by weight by 20 parts of nitrendipines, 2 parts of minipresses; Adjuvant contains 99 parts of starch, 48 parts of Icing Sugar, 25 parts in dextrin, 2 parts of magnesium stearate, 4 parts of Pulvis Talci.
The manufacture method of compositions B is as follows:
(1) granulates: take by weighing active ingredient nitrendipine, minipress, starch, Icing Sugar, dextrin mix homogeneously by required parts by weight.Iron alkane ketone alcoholic solution with 5% polyethylene pyrrole and be made into soft material, granulate with oscillating granulator.The preparation method that above-mentioned 5% polyethylene pyrrole irons alkane ketone alcoholic solution irons alkane ketone for taking by weighing 5 gram polyethylene pyrroles, be dissolved in 100 milliliters the dehydrated alcohol, cause wherein 5% polyethylene pyrrole irons all evaporations in drying course of alkane ketone alcoholic solution, so its weight can be ignored.Icing Sugar is that sucrose is pulverized the back and crossed the fine powder that 100 mesh sieves obtain, and the purpose that adds it is a particulate compressibility when increasing tabletting.
(2) oven dry: granule is dried down at 100 ℃.
(3) granulate: after the drying, use the pelletizing machine granulate.
(4) mix tabletting: adding magnesium stearate and Pulvis Talci then, behind the mixing, is the tablet that 6 millimeters No. 6 drift tablettings are made every 100mg with diameter.
Claims (2)
1. a hypotensor composition is characterized in that by weight, and active ingredient is made up of for 25 parts 20 parts of nitrendipines, 2 parts of minipresses, hydrochlorothiazide; Adjuvant is by 136 parts of starch, 72 parts of Icing Sugar, 36 parts in dextrin, 3 parts of magnesium stearate, 6 parts of compositions of Pulvis Talci.
2. the manufacture method of hypotensor composition is as follows according to claim 1:
(1) granulates: take by weighing active ingredient nitrendipine, minipress, hydrochlorothiazide by required parts by weight, reach supplementary product starch, Icing Sugar, dextrin mix homogeneously, iron alkane ketone alcoholic solution with 5% polyethylene pyrrole and be made into soft material, granulate with oscillating granulator;
(2) oven dry: granule is dried down at 100 ℃;
(3) granulate: after the drying, whole with pelletizing machine;
(4) mix tabletting: add magnesium stearate and Pulvis Talci, behind the mixing, be pressed into the tablet of every 100mg～150mg with drift.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100444031A CN100374113C (en) | 2006-03-01 | 2006-03-01 | Hypotensor composition |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100444031A CN100374113C (en) | 2006-03-01 | 2006-03-01 | Hypotensor composition |
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|---|---|
| CN1810243A CN1810243A (en) | 2006-08-02 |
| CN100374113C true CN100374113C (en) | 2008-03-12 |
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|---|---|---|---|
| CNB2006100444031A Expired - Fee Related CN100374113C (en) | 2006-03-01 | 2006-03-01 | Hypotensor composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101548985B (en) * | 2009-05-15 | 2011-05-18 | 赖福平 | Compound antihypertensive drug and preparation method thereof |
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- 2006-03-01 CN CNB2006100444031A patent/CN100374113C/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| 抗高血压药联合应用的现状及评价. 窦学廉.天津药学，第14卷第5期. 2002 * |
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