CN105125560A - Hydrochlorothiazide compound composition and preparing method - Google Patents
Hydrochlorothiazide compound composition and preparing method Download PDFInfo
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- CN105125560A CN105125560A CN201510641453.7A CN201510641453A CN105125560A CN 105125560 A CN105125560 A CN 105125560A CN 201510641453 A CN201510641453 A CN 201510641453A CN 105125560 A CN105125560 A CN 105125560A
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Abstract
The invention discloses a hydrochlorothiazide compound composition and a preparing method. The hydrochlorothiazide compound composition is prepared from, by weight, 25-50 parts of hydrochlorothiazide, 30-40 parts of potassium citrate, 150-180 parts of diluent, 10-15 parts of surfactant, 160-200 parts of disintegrating agent and 15-25 parts of lubricating agent. The preparing method of the composition comprises the steps of material preparing, pelleting and tabletting. According to the hydrochlorothiazide compound composition and the preparing method, after two or more kinds of medicine is made into a compound preparation, the effective proportion of the medicine is high, medicine is convenient to take, the pressure dropping effect is good, the survival rate of a medicine taking patient is increased, the amount of accessories and the packaging cost are reduced, and mass production is facilitated.
Description
Technical field
The invention belongs to medical art, particularly a kind of hydrochlorothiazide Compound compositions and preparation method.
Background technology
Hydrochlorothiazide is diuretic, antihypertensive.Mainly be applicable to cardiac edema, hepatic edema and renal edema, the edema caused as nephrotic syndrome, acute glomerulonephritis, chronic renal failure and adrenocortical hormone and hyperestrogenism, hypertension, urine spring disease.
Hydrochlorothiazide is oral rapidly but not exclusively, bioavailability is 60 ~ 80%, and feed can increase absorbtivity, may be relevant at the increased retention of small intestinal with medicine.Produce diuresis after oral 2h, peak time is 4h, produces hypotensive effect after 3 ~ 6h, and acting duration is 6 ~ 12h.This medicine part is combined with plasma protein, and protein binding rate is 40%, and another part enters in cell, Placenta Hominis.Eliminating phase incipient stage haemoconcentration after this medicine absorbs declines very fast, and later blood drug level declines and obviously slows down, and may be because after-stage medicine enters in erythrocyte relevant, mainly with original shape by homaluria.This product half-life T1/2 is 15h, and congestive heart failure, impaired renal function person extend.This product 50 ~ 70% is discharged by urine with original shape, also can through galactopoiesis.
Hydrochlorothiazide mechanism of drug action mainly suppresses distal tubule leading portion and proximal tubule (acting on lighter) to be received the suction of sodium chloride, thus increases the Na of distal tubule and collecting tubule
+-K
+exchange, K
+secretion increasing.Prolonged application is appropriate to the occasion suitably supplements potassium salt.Take inconvenience, independent tableting aid consumption is relatively many, and packing cost is high, not only facilitates medication, and reduces adjuvant and packing cost, be conducive to large production after therefore two kinds or two or more medicines being made compound preparation.
Summary of the invention
The present invention seeks to the defect in order to overcome two kinds or two or more Drug combination, propose one can diuresis, antihypertensive pharmaceutical composition, two kinds of medicines combine by the present invention, and the effective ratio of medicine is high, taking convenience.
The present invention seeks to be realized by following technical scheme:
A kind of hydrochlorothiazide Compound compositions, component and the parts by weight of said composition comprise: hydrochlorothiazide 25 ~ 50 parts, potassium citrate 30 ~ 40 parts, diluent 150 ~ 180 parts, 10 ~ 15 parts, surfactant, disintegrating agent 160 ~ 200 parts, lubricant 15 ~ 25 parts.
The object of the invention can also be realized by following technical scheme:
A kind of hydrochlorothiazide Compound compositions, component and the parts by weight of said composition comprise: hydrochlorothiazide 25 parts, potassium citrate 30 parts, diluent 150 parts, 10 parts, surfactant, disintegrating agent 160 parts, lubricant 15 parts.
A kind of hydrochlorothiazide Compound compositions, component and the parts by weight of said composition comprise: hydrochlorothiazide 50 parts, potassium citrate 40 parts, diluent 180 parts, 15 parts, surfactant, disintegrating agent 200 parts, lubricant 25 parts.
A kind of hydrochlorothiazide Compound compositions, component and the parts by weight of said composition comprise: hydrochlorothiazide 30 parts, potassium citrate 35 parts, diluent 170 parts, 12 parts, surfactant, disintegrating agent 180 parts, lubricant 20 parts.
A kind of hydrochlorothiazide Compound compositions, diluent comprises at least one in mannitol, amylum pregelatinisatum, microcrystalline Cellulose.
A kind of hydrochlorothiazide Compound compositions, surfactant comprise sucrose ester, fatty acid Pyrusussuriensis smooth at least one.
A kind of hydrochlorothiazide Compound compositions, disintegrating agent comprises that carboxymethyl starch is received, at least one in low-substituted hydroxypropyl cellulose.
A kind of hydrochlorothiazide Compound compositions, lubricant comprises at least one in magnesium stearate, micropowder silica gel, Pulvis Talci.
Present invention also offers a kind of preparation method of hydrochlorothiazide Compound compositions, comprise the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of described a kind of hydrochlorothiazide Compound compositions and parts by weight, wherein hydrochlorothiazide, potassium citrate pulverized 120 mesh sieves respectively, and 80 mesh sieves pulverized respectively by diluent, surfactant, disintegrating agent, lubricant;
2) granulate, by hydrochlorothiazide, diluent is appropriate, surfactant is appropriate, disintegrating agent is appropriate, the appropriate mix homogeneously wet granulation of lubricant 20 order granulate obtain granule A, by potassium citrate, the even wet granulation of the diluent of surplus, surfactant, disintegrating agent, mix lubricant also 30 order granulate obtains granule B;
3) tabletting, adopts high speed bi-layer tablet press by granule A and granule B tabletting, and first press granule B to press granule A again, specification is with hydrochlorothiazide content meter 20 ~ 50mg/ sheet.
Beneficial effect of the present invention
Two kinds of medicine hydrochlorothiazide, potassium citrate combine by the present invention, and overcome the appropriate to the occasion suitably supplementary potassium salt of prolonged application hydrochlorothiazide, take inconvenience, independent tableting aid consumption is relatively many, the defect that packing cost is high.After the present invention makes compound preparation two kinds or two or more medicines, not only the effective ratio of medicine is high, facilitates medication, and antihypertensive effect is good, and improves the survival rate of medication patient, reduces supplementary product consumption and packing cost, is conducive to large production.
Detailed description of the invention
According to following embodiment, the present invention may be better understood.But those skilled in the art will readily understand, concrete material proportion, process conditions and result thereof described by embodiment only should can not limit the present invention described in detail in claims yet for illustration of the present invention.
Embodiment 1
A kind of hydrochlorothiazide Compound compositions, component and the parts by weight of said composition comprise: hydrochlorothiazide 25 parts, potassium citrate 30 parts, 150 parts, mannitol, sucrose ester 10 parts, sodium carboxymethyl cellulose 160 parts, magnesium stearate 15 parts.
A preparation method for hydrochlorothiazide Compound compositions, comprises the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of described a kind of hydrochlorothiazide Compound compositions and parts by weight, wherein hydrochlorothiazide, potassium citrate pulverized 120 mesh sieves respectively, and mannitol, sucrose ester, sodium carboxymethyl cellulose, magnesium stearate pulverized 80 mesh sieves respectively;
2) granulate, by hydrochlorothiazide, mannitol parts by weight 1/2nd, sucrose ester parts by weight 1/2nd, sodium carboxymethyl cellulose parts by weight 1/2nd, 1/2nd mix homogeneously wet granulations of magnesium stearate parts by weight 20 order granulate obtain granule A, by potassium citrate, mannitol parts by weight 1/2nd, sucrose ester parts by weight 1/2nd, 1/2nd of sodium carboxymethyl cellulose parts by weight, 1/2nd mix homogeneously wet granulations of magnesium stearate parts by weight 30 order granulate obtain granule B;
3) tabletting, adopts high speed bi-layer tablet press by granule A and granule B tabletting, and first press granule B to press granule A again, specification is with hydrochlorothiazide content meter 25mg/ sheet.
Usage and dosage: oral, every day 1 ~ 2 time, each 1 ~ 2 or follow the doctor's advice.
Embodiment 2
A kind of hydrochlorothiazide Compound compositions, component and the parts by weight of said composition comprise: hydrochlorothiazide 50 parts, potassium citrate 40 parts, amylum pregelatinisatum 110 parts, microcrystalline Cellulose 70 parts, smooth 15 parts of fatty acid Pyrusussuriensis, low substituted hydroxy-propyl fiber 200 parts, micropowder silica gel 25 parts.
A preparation method for hydrochlorothiazide Compound compositions, comprises the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of described a kind of hydrochlorothiazide Compound compositions and parts by weight, wherein hydrochlorothiazide, potassium citrate pulverized 120 mesh sieves respectively, and amylum pregelatinisatum, microcrystalline Cellulose, fatty acid Pyrusussuriensis are smooth, 80 mesh sieves were pulverized in low substituted hydroxy-propyl fiber, micropowder silica gel respectively;
2) granulate, by hydrochlorothiazide, amylum pregelatinisatum, the smooth parts by weight of fatty acid Pyrusussuriensis 1/2nd, low substituted hydroxy-propyl fibre weight number 1/2nd, 1/2nd mix homogeneously wet granulations of micropowder silica gel parts by weight 20 order granulate obtain granule A, by potassium citrate, microcrystalline Cellulose, the smooth parts by weight of fatty acid Pyrusussuriensis 1/2nd, 1/2nd of low substituted hydroxy-propyl fibre weight number, 1/2nd mix homogeneously wet granulations of micropowder silica gel parts by weight 30 order granulate obtain granule B;
3) tabletting, adopts high speed bi-layer tablet press by granule A and granule B tabletting, and first press granule B to press granule A again, specification is with hydrochlorothiazide content meter 35mg/ sheet.
Usage and dosage: oral, every day 1 ~ 2 time, each 1 ~ 2 or follow the doctor's advice.
Embodiment 3
A kind of hydrochlorothiazide Compound compositions, component and the parts by weight of said composition comprise: hydrochlorothiazide 30 parts, potassium citrate 35 parts, microcrystalline Cellulose 170 parts, smooth 12 parts of fatty acid Pyrusussuriensis, carboxymethyl starch sodium 180 parts, Pulvis Talci 20 parts.
A preparation method for hydrochlorothiazide Compound compositions, comprises the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of described a kind of hydrochlorothiazide Compound compositions and parts by weight, wherein hydrochlorothiazide, potassium citrate pulverized 120 mesh sieves respectively, and microcrystalline Cellulose, fatty acid Pyrusussuriensis are smooth, 80 mesh sieves pulverized respectively by carboxymethyl starch sodium, Pulvis Talci;
2) granulate, by hydrochlorothiazide, microcrystalline Cellulose parts by weight 1/2nd, the smooth parts by weight of fatty acid Pyrusussuriensis 1/2nd, carboxymethyl starch sodium parts by weight 1/2nd, 1/2nd mix homogeneously wet granulations of Pulvis Talci parts by weight 20 order granulate obtain granule A, by potassium citrate, microcrystalline Cellulose parts by weight 1/2nd, the smooth parts by weight of fatty acid Pyrusussuriensis 1/2nd, 1/2nd of carboxymethyl starch sodium parts by weight, 1/2nd mix homogeneously wet granulations of Pulvis Talci parts by weight 30 order granulate obtain granule B;
3) tabletting, adopts high speed bi-layer tablet press by granule A and granule B tabletting, and first press granule B to press granule A again, specification is with hydrochlorothiazide content meter 50mg/ sheet.
Usage and dosage: oral, every day 1 ~ 2 time, each 1 ~ 2 or follow the doctor's advice.
Embodiment 4
Friability inspection of the present invention
Check according to " Chinese Pharmacopoeia " 2010 editions (two) annex XG tablet friability inspection technique.
Instrument: friability tester.
Method: get some, makes its gross weight be about 6.5g; Blow away the powder come off with hair-dryer, precise weighing, put in cylinder, rotate 100 times.Take out, with method removing powder, precise weighing, less loss weight must not cross 1%, and the sheet that must not detect fracture, be full of cracks and pulverize.This test is general only to be done 1 time.As less loss weight more than 1% time, should recheck 2 times, the average less loss weight of 3 times must not cross 1%, and must not detect fracture, be full of cracks and pulverize sheet.
Result: embodiments of the invention 1-3 gained sample all conforms with the regulations through friability test inspection.
Embodiment 5
Dissolution test of the present invention
According to dissolution test method (Chinese Pharmacopoeia version in 2010 two annex XD second methods), take water as solvent, rotating speed is 50 turns per minute, and water temperature 32 ± 0.5 DEG C operates in accordance with the law.Measure the dissolution of sample hydrochlorothiazide obtained by embodiment 1-3 respectively.Detect dissolution (%) by HPLC and the results are shown in following table.
| Sample | Embodiment 1 | Embodiment 2 | Embodiment 3 |
| Dissolution | 97.15 | 96.51 | 99.01 |
Conclusion: result shows that compound dissolution of the present invention meets conjunction requirement.
Embodiment 6
Pharmacodynamic analysis of the present invention
To the hypotensive activity of Hypertensive Rats, adopt spontaneous hypertensive rat (SHR) male rat in 20 ~ 26 week age, single dose, with compound dose oral administration respectively, detects its hypotensive effect.Rat tail pressure is measured by I type rat tail pressure heart rate measurement instrument.
Positive controls adopts folk prescription single oral dose administration hydrochlorothiazide 0.25mg/kg/d, potassium citrate 0.3mg/kg/d.
The compositions that test group adopts compound recipe single oral dose administration hydrochlorothiazide 0.25mg/kg/d, potassium citrate 0.3mg/kg/d and the embodiment of the present invention 1 to prepare.
Result of the test:
Folk prescription single dose systolic pressure can reduce by 5.65 ~ 28.55mmHg, diastolic pressure reduce by 8.79 ~ 11.56mmHg, year survival rate be 70.4%.Compound recipe single dose systolic pressure can reduce by 14.26 ~ 19.48mmHg, and diastolic pressure reduces by 15.46 ~ 19.32mmHg, year survival rate be 80.9%, antihypertensive effect is good, and substantially increases the survival rate of medication Mus.
Conclusion:
This compound can better blood pressure lowering, and improves the survival rate of medication Mus.
Above embodiment is only for illustrating technical conceive of the present invention and feature; its object is to allow person skilled in the art understand content of the present invention and to be implemented; can not limit the scope of the invention with this; all equivalences done according to spirit of the present invention change or modify, and all should be encompassed in protection scope of the present invention.
Claims (9)
1. a hydrochlorothiazide Compound compositions, it is characterized in that, component and the parts by weight of said composition comprise: hydrochlorothiazide 25 ~ 50 parts, potassium citrate 30 ~ 40 parts, diluent 150 ~ 180 parts, 10 ~ 15 parts, surfactant, disintegrating agent 160 ~ 200 parts, lubricant 15 ~ 25 parts.
2. a kind of hydrochlorothiazide Compound compositions according to claim 1, it is characterized in that, component and the parts by weight of said composition comprise: hydrochlorothiazide 25 parts, potassium citrate 30 parts, diluent 150 parts, 10 parts, surfactant, disintegrating agent 160 parts, lubricant 15 parts.
3. a kind of hydrochlorothiazide Compound compositions according to claim 1, it is characterized in that, component and the parts by weight of said composition comprise: hydrochlorothiazide 50 parts, potassium citrate 40 parts, diluent 180 parts, 15 parts, surfactant, disintegrating agent 200 parts, lubricant 25 parts.
4. a kind of hydrochlorothiazide Compound compositions according to claim 1, it is characterized in that, component and the parts by weight of said composition comprise: hydrochlorothiazide 30 parts, potassium citrate 35 parts, diluent 170 parts, 12 parts, surfactant, disintegrating agent 180 parts, lubricant 20 parts.
5. a kind of hydrochlorothiazide Compound compositions according to any one of Claims 1 to 4, it is characterized in that, diluent comprises at least one in mannitol, amylum pregelatinisatum, microcrystalline Cellulose.
6. a kind of hydrochlorothiazide Compound compositions according to any one of Claims 1 to 4, is characterized in that, surfactant comprise sucrose ester, fatty acid Pyrusussuriensis smooth at least one.
7. a kind of hydrochlorothiazide Compound compositions according to any one of Claims 1 to 4, is characterized in that, disintegrating agent comprises that carboxymethyl starch is received, at least one in low-substituted hydroxypropyl cellulose.
8. a kind of hydrochlorothiazide Compound compositions according to any one of Claims 1 to 4, it is characterized in that, lubricant comprises at least one in magnesium stearate, micropowder silica gel, Pulvis Talci.
9. a preparation method for hydrochlorothiazide Compound compositions, is characterized in that, comprises the following steps:
1) get the raw materials ready, get the raw materials ready according to the component of a kind of hydrochlorothiazide Compound compositions described in any one of Claims 1 to 4 and parts by weight, wherein hydrochlorothiazide, potassium citrate pulverized 120 mesh sieves respectively, and 80 mesh sieves pulverized respectively by diluent, surfactant, disintegrating agent, lubricant;
2) granulate, by hydrochlorothiazide, diluent is appropriate, surfactant is appropriate, disintegrating agent is appropriate, the appropriate mix homogeneously wet granulation of lubricant 20 order granulate obtain granule A, by potassium citrate, the even wet granulation of the diluent of surplus, surfactant, disintegrating agent, mix lubricant also 30 order granulate obtains granule B;
3) tabletting, adopts high speed bi-layer tablet press by granule A and granule B tabletting, and first press granule B to press granule A again, specification is with hydrochlorothiazide content meter 25 ~ 50mg/ sheet.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115518043A (en) * | 2022-10-12 | 2022-12-27 | 江苏集萃新型药物制剂技术研究所有限公司 | Controlled release composition, granules, tablets and preparation method thereof |
Citations (2)
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| US4966776A (en) * | 1983-04-11 | 1990-10-30 | Board Of Regents, The University Of Texas System | Compositions and methods of treating calcium renal stones |
| CN102885789A (en) * | 2012-04-05 | 2013-01-23 | 常州制药厂有限公司 | Preparation method of compound preparation for treating high blood pressure |
-
2015
- 2015-09-30 CN CN201510641453.7A patent/CN105125560A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4966776A (en) * | 1983-04-11 | 1990-10-30 | Board Of Regents, The University Of Texas System | Compositions and methods of treating calcium renal stones |
| CN102885789A (en) * | 2012-04-05 | 2013-01-23 | 常州制药厂有限公司 | Preparation method of compound preparation for treating high blood pressure |
Non-Patent Citations (4)
| Title |
|---|
| MITRAL NASERI等: "role of high-dose hydrochlorothiazide in idiopathic hypercalciuric urolithiasis of childhood", 《IRANIAN JOURNAL OF KIDNEY DISEASES》 * |
| 刘爱民 等: "中西医结合治疗儿童特发性高钙尿症", 《浙江中西医结合杂志》 * |
| 张惠琴 等: "枸橼酸钾对高血压患者血压的影响", 《河北医学》 * |
| 高明明: "噻嗪类利尿剂治疗高血压的定位", 《临床药物治疗杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115518043A (en) * | 2022-10-12 | 2022-12-27 | 江苏集萃新型药物制剂技术研究所有限公司 | Controlled release composition, granules, tablets and preparation method thereof |
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