CN1528311A - Terazosin Hydrochloride drop pill and preparing method thereof - Google Patents
Terazosin Hydrochloride drop pill and preparing method thereof Download PDFInfo
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- CN1528311A CN1528311A CNA031433405A CN03143340A CN1528311A CN 1528311 A CN1528311 A CN 1528311A CN A031433405 A CNA031433405 A CN A031433405A CN 03143340 A CN03143340 A CN 03143340A CN 1528311 A CN1528311 A CN 1528311A
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- terazosin
- terazosin hydrochloride
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- polyethylene glycol
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Abstract
The present invention utilizes ultramicropulverization and dripping pill preparation production process to make terazosin hydrochloride dripping pills, and can attain the goal of raising disintegration and dissolution speed, quickly obtaining therapeutic effect, raising stability of medicine, reducing dose of auxiliary material, reducing production cost and convenient administration. Said pill not only can be sucked, but also can be swallowed, and its compliance property is good.
Description
Technical field
The present invention relates to a kind of pharmaceutical product and preparation method thereof, specifically terazosin hydrochloride drop pill and preparation method thereof.
Background technology
The symptom relevant with benign prostatic hyperplasia (BPH) relates to bladder outlet and blocks, and it comprises two elements: static part and dynamic part.Static part is the result that prostate increases.In a period of time, prostate can constantly enlarge.Yet clinical research shows that the seriousness of prostatic size and BPH symptom or the degree of urethral obstruction are irrelevant.Dynamic part is the function that prostate and neck of bladder smooth muscle tone increase, and causes the narrow of bladder outlet.Smooth muscle tone is by α
1The sympathetic stimulation effect mediation of-adrenoreceptor, this receptor enriches in the neck of bladder of prostate, prostatic utriculus.Give the α in the sx and urine flow velocity improvement and neck of bladder and prostate behind the terazosin
1It is relevant that-adrenoreceptor is blocked caused smooth muscle loosening.Because few relatively α is arranged in body of bladder
1-adrenoreceptor, so terazosin can alleviate the obstruction of bladder outlet and not influence the contraction of bladder.
Terazosin is studied in 1222 examples have the male patient of BPH symptom.In the research of three blanks, carried out the symptom evaluation in about 24 hours after the administration and uroflometer is measured.Adopt Boyarsky Index that symptom is carried out quantitatively.(impression that hesitancy in urination, discontinuous, the size that finishes to drip urine, urine stream in the back of urinating and pressure damage, bladder are not emptied completely) and stimulation (frequent micturition on nocturia, daytime, urgent micturition dysuria) symptom are blocked in the evaluation of investigation form, 9 symptoms are separately by 0～3 marking, and gross score is 27.Terazosin is to individuality the analysis showed that of symptom influence of urinating, compare with blank, terazosin obviously improves the size of hesitancy in urination, discontinuous, urine stream and impression that pressure damage, bladder are not emptied completely, urinates and finish frequent micturition and the nocturia that urine, daytime are dripped in the back.
The general function and the symptom of urinating have been carried out overall merit, compared with the patient of blank treatment, the patient who treats with terazosin has obviously (P≤0.001) big overall improvement.
In the long term test, terazosin all has clear improvement symptom and urine flow velocity maximum mark, and the prompting terazosin makes smooth muscle cell lax.Although blocking-up α
1-adrenoreceptor also reduces the blood pressure that increases the hypertensive patient cause because of peripheral vascular resistance, but does not cause significantly blood pressure reduction effect clinically during the treatment of normotensive BPH andropathy human terazosin.
In animal, thereby terazosin reduces blood pressure by reducing total peripheral vascular resistance.As if the vasodilation of terazosin, blood pressure reduction effect mainly are by α
1The blocking-up of-adrenoreceptor is caused.In 15 minutes, terazosin reduces blood pressure gradually after administration.
Suffer from that slight (about 77%, (about 23%, diastolic pressure 105～115mmHg) hypertensive patients are according to 5～20mg/ days accumulated dose, once a day or give terazosin for twice and carry out clinical trial for diastolic pressure 95～105mmHg) or moderate.The same with all alpha-2 antagonists, because terazosin can make blood pressure descend rapidly first or after the preceding administration several times, therefore initial dose is 1mg, adjusts to a certain fixed dosage then or adjusts to a certain specific blood pressure terminal point (diastolic pressure of dorsal position is 90mmHg usually).
The end of term between administration (common 24 hours) is measured blood pressure, and the result shows that hypotensive effect continues whole interval, and usually, the systolic pressure of dorsal position reduces than blank big 5～10mmHg, the big 3.5～8mmHg of the reduction of diastolic pressure.Measured in 24 hours after the administration, heart rate does not change.
The amount and the prazosin that cause blood pressure response are similar, but are lower than hydrochlorothiazide.
The terazosin small dose group reduces patient's T-CHOL, low-density and very low density lipoprotein (VLDL) statistically significantly, but high density lipoprotein and triglyceride are not obviously changed.
After taking medicine, the male patient absorbs fully basically.Immediately after meals is taken medicine minimum to the influence of degree of absorption, but makes the plasma concentration peak time postpone about 40 minutes.The liver first pass metabolism of terazosin is very little.Reached peak value in about 1 hour after taking medicine, the half-life is about 12 hours.In the research of age, find terazosin pharmacokinetics influence, the patient at 〉=70 years old and 20～39 years old age, its plasma half-life was respectively 14.0 and 11.4 hours.Plasma protein binding rate is 90%～94%.About 40% through homaluria, and about 60% discharges with feces.List marketing at present tablet and capsule, the clinical benign prostate hyperplasia that is used for the treatment of arranged.Also can be used for treating hypertension, can use separately or share with other antihypertensive drug such as diuretic or beta-adrenergic blocking agent.
The terazosin hydrochloride mildly bitter flavor, odorless almost, molten in the water part omitted, its tablet or capsule disintegration time are long, absorption difference, and bioavailability is low, the supplementary product consumption ratio is big, child, old people, bed patient and dysphagia patients are taken inconvenience, and compliance is poor, have influenced the performance of terazosin hydrochloride therapeutical effect.
The present invention makes the terazosin hydrochloride drop pill by using ultramicro communication technique and dropping pill formulation Technology exactly, thereby overcomes terazosin and capsular above defective, and the therapeutical effect of terazosin hydrochloride is given full play to.
Summary of the invention
The terazosin hydrochloride drop pill of making by using ultramicro communication technique and dropping pill formulation Technology not only have disintegrate molten loose fast, steady quality, the pill volume is little, both can swallow also can buccal, easy to carry and use, onset is rapid, compliance is good, be particularly suitable for the characteristics that child, old people, bed patient and dysphagia patients are taken, but also has working condition and production equipment is simple, production cost is low, compares the advantage that supplementary product consumption reduces with tablet or capsule, has demonstrated fully the new drug research exploitation spirit that people-oriented.
For achieving the above object, the present invention by the following technical solutions: the terazosin hydrochloride fine powder of 1 weight portion through micronizing is added in 5～20 weight portion molten matrix, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
The chemical name of terazosin hydrochloride among the present invention (Terazosin Hydrochloride) is 1-(4-amino-6,7-dimethoxy-2-quinazolyl)-4-(oxolane-2-formyl) piperazine hydrochloride dihydrate,
Structural formula is
Molecular formula is
C
19H
25N
5O
4HCl2H
2O, molecular weight are 459.93.
Substrate among the present invention includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.
Coolant among the present invention includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.
Below through detecting to beneficial effect of the present invention as directed
One, detects index and method
Disintegrate (molten loosing) time limit: check according to inspection technique disintegration (two appendix XA of Chinese Pharmacopoeia version in 2000).
Two, commercially available terazosin disintegration time testing result: 53 minutes
Three, example 1 sample disintegrate (molten loosing) time detecting result: 3 minutes
Four, example 2 sample disintegrates (molten loosing) time detecting result: 3 minutes
Five, example 3 sample disintegrates (molten loosing) time detecting result: 6 minutes
Six, example 4 sample disintegrates (molten loosing) time detecting result: 9 minutes
Seven, example 5 sample disintegrates (molten loosing) time detecting result: 12 minutes
Eight, example 6 sample disintegrates (molten loosing) time detecting result: 16 minutes
The specific embodiment
One, example 1
Prescription:
Terazosin hydrochloride 2g
Polyethylene glycol 6000 18g
Make 1000
Method for making: the terazosin hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused polyethylene glycol 6000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Two, example 2
Prescription:
Terazosin hydrochloride 2g
Macrogol 4000 18g
Make 1000
Method for making: the terazosin hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused Macrogol 4000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Three, example 3
Prescription:
Terazosin hydrochloride 2g
Polyethylene glycol 6000 8g
Macrogol 4000 10g
Make 1000
Method for making: the terazosin hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused Macrogol 4000 and the polyethylene glycol 6000 mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Four, example 4
Prescription:
Terazosin hydrochloride 2g
Glyceryl monostearate 18g
Make 1000
Method for making: the terazosin hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused glyceryl monostearate substrate, and mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.
Five, example 5
Prescription:
Terazosin hydrochloride 2g
Polyethylene glycol 6000 13g
Poloxamer 5g
Make 1000
Method for making: the terazosin hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused polyethylene glycol 6000 and the poloxamer mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Six, example 6
Prescription:
Terazosin hydrochloride 2g
Glyceryl monostearate 15g
Poloxamer 3g
Make 1000
Method for making: get the mixing fine powders that terazosin hydrochloride and poloxamer cross 200 mesh sieves through micronizing and be added in the fused glyceryl monostearate substrate, mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.
Claims (4)
1. terazosin hydrochloride drop pill and preparation method thereof is characterized in that: the terazosin hydrochloride fine powder of 1 weight portion through micronizing is added in 5～20 weight portion molten matrix, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
2. the molecular formula of the described terazosin hydrochloride of claim 1 is C
19H
25N
5O
4HCl2H
2O, molecular weight are 459.93, and structural formula is
HCl, 2H
2O
3. the described substrate of claim 1 includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.
4. the described coolant of claim 1 includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031433405A CN1528311A (en) | 2003-09-27 | 2003-09-27 | Terazosin Hydrochloride drop pill and preparing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031433405A CN1528311A (en) | 2003-09-27 | 2003-09-27 | Terazosin Hydrochloride drop pill and preparing method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1528311A true CN1528311A (en) | 2004-09-15 |
Family
ID=34286564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031433405A Pending CN1528311A (en) | 2003-09-27 | 2003-09-27 | Terazosin Hydrochloride drop pill and preparing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1528311A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100339082C (en) * | 2004-07-08 | 2007-09-26 | 天津美伦医药集团有限公司 | Terazosin hydrochloride dripping pills, and its prepn. method |
| CN102018685B (en) * | 2009-09-16 | 2013-06-05 | 河北奥星集团药业有限公司 | Terazosin pellicle and preparation method thereof |
-
2003
- 2003-09-27 CN CNA031433405A patent/CN1528311A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100339082C (en) * | 2004-07-08 | 2007-09-26 | 天津美伦医药集团有限公司 | Terazosin hydrochloride dripping pills, and its prepn. method |
| CN102018685B (en) * | 2009-09-16 | 2013-06-05 | 河北奥星集团药业有限公司 | Terazosin pellicle and preparation method thereof |
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| PB01 | Publication | ||
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| WD01 | Invention patent application deemed withdrawn after publication |