CN1698615A - Suppository containing prazosin hydrochloride, its preparation method and application - Google Patents
Suppository containing prazosin hydrochloride, its preparation method and application Download PDFInfo
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- CN1698615A CN1698615A CN 200410018448 CN200410018448A CN1698615A CN 1698615 A CN1698615 A CN 1698615A CN 200410018448 CN200410018448 CN 200410018448 CN 200410018448 A CN200410018448 A CN 200410018448A CN 1698615 A CN1698615 A CN 1698615A
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Abstract
The invention provides a suppository containing prazosin hydrochloride wherein the suppository comprises prazosin hydrochloride as active constituent and medicinal auxiliary materials. Clinical tests show that the suppository is effective for patients with prostate hypertrophy and hyperplasia, and can be used for substituting surgical treatment. The suppository has the advantages of quick action and high biological availability. The invention also discloses its preparation.
Description
Technical field
The invention belongs to technical field of medicine.Be specifically related to a kind of suppository and preparation method and application of hydrochloric prazosin.
Background technology
Minipress (Prazosin) Prazosin Hydrochloride (minipress); the pharmacological action of chemical name: 1-(4-amino-6,7-dimethylamino-2-quinazoline)-4-(2-furanylcarbonyl)-piperazine hydrochloride is that minipress is an alpha-adrenergic blocking agent.
Formula I
This chemical compound is mainly as the active component for the treatment of hypertension agents.But show that in Europe and the Japanese clinical trial of carrying out antihypertensive alpha 1 adrenergic receptor blocker minipress is to benign prostatic hyperplasia (Benign prostatic hypertrophy; B.P.H) mitigation symptoms significantly, the symptom that can be used as the new treatment, particularly patient that substitute operation does not reach the order of severity or the patient that must perform the operation is reluctant, can not tolerate surgery person.
Britain urinary system expert milroy doctor studies the application of prazosin, at one 80 routine BPH patients are scheduled to last in the research that placebo is arranged all around, the treatment group speed of urinating is obviously accelerated, and number of times reduces, though＞70% patient's sx, the bladder pressure no change.Carried out research in three months in 93 examples again later on, still having urinates speeds up and the effect of sx, and bladder pressure descends and noresidue urine person obviously increases when particularly urinating, and blood pressure does not have change.
Japan professor Kondo reports that patient's symptom is clearly better in one 20 routine BPH patient's the open research, total effective rate 85%, no side effects.
Prostatic contraction is controlled by alpha 1 adrenergic receptor, and prostatic secretion is controlled by the poisonous fungus cholinoceptor.α 1 Rd is the highest in bladder bottom and prostate, and being distributed with of this Rd is beneficial to the α beta blocker and plays a role.The orthosympathetic excited of patient for example stimulates: direct stimulation, drink coffee, eat seafood, meat box even clothes cough rhinorrhea drug anesthesia flavin, factors such as phenylpropanolamine all can be brought out urine retention.The above-mentioned minipress that shows can reduce the resistance of bladder outlet and not influence the contraction of smooth muscle, alleviates urethral obstruction, and the dysuria symptom is improved, and dynamic property is blocked and is eliminated.
Summary of the invention
Technical problem to be solved by this invention is to adopt the active remedy of minipress as active component research design treatment benign prostatauxe.
The invention provides a kind of suppository (No. 2, the precious bolt in prostatitis) of hydrochloric prazosin, this suppository comprises following composition (seeing Table 1):
| Sequence number | The name of an article | Every piece of content | Per 10,000 pieces of content |
| ????1 | Minipress | ????3.5-5.0mg | ????35-50g |
| ????2 | Citric acid | ????3mg | ????30g |
| ????3 | Laurocapram | ????40-60mg | ????400-600g |
| ????4 | Propylene glycol (1,2) | ????20mg | ????200g |
| ????5 | Tween 80 | ????38mg | ????380g |
| ????6 | Sodium laurylsulfate | ????8mg | ????80g |
| ????7 | Sorbester p18 | ????20mg | ????200g |
| ????8 | Semi-synthetic Fructus Litseae oils and fats #36 | ????1.40g | ????14000g |
| Weigh for theoretical every piece | ????1.53-1.56 | ||
| Fusing point | ????33-35℃ |
Suppository treatment benign prostatauxe of the present invention is based on following principle:
The urinary tract obstruction that benign prostatauxe (B, P, H) patient causes is relevant with two factors, and a dynamic property factor is promptly because the neurogenic tonus of neck of bladder and prostate smooth muscle; Another is that the firm static factor is promptly because the increase of prostate volume.
The observation on Clinical Application of the suppository of hydrochloric prazosin of the present invention (No. 2, the precious bolt in prostatitis) treatment prostate hyperplasia is as follows by Shanghai core Ji hospital result of the test:
One, materials and methods
1. case is selected:
26 routine prostate hyperplasia patients, in age 51-81 year, average 70.81 ± 7.99 years old, course of disease 5-10 did the urethral catheterization history except that urine retention once takes place 2 examples, and surplus all do not have a urine retention history, and all cases were all once used QIANLIEKANG.HL286, treatments such as norfloxacin require patient to stop other drug during treating.
2. pharmaceutical compositions and administrated method:
The precious bolt of reference substance prostate adopts traditional Chinese medical science blood circulation promoting and blood stasis dispelling No. 1, attacking the theory of real eliminating stagnation selects for use all kinds of Chinese medicines to refine and refining forming, and combine with synthetic drug and to form suppository, may have the inhibition proliferation of fibrous tissue through clinical verification, reduce inflammation and antiinflammation such as is oozed out in the part.Prostata tissue is dwindled, alleviate unobstructed micturition.
No. 2, the precious bolt in prostatitis of the present invention
No. 1, the precious bolt in this group case 12 example employing prostatitis, 14 examples adopt the precious bolt in prostatitis No. 2, and administrated method is each one piece of Serb anus of morning and evening, lies on one's side 20 minutes, and 2 months is a course of treatment.
3. observation index: before the medication and medication observe following all after 2 months respectively:
3.1. clinical symptoms: comprise the nocturia number of times, the dysuria degree, daytime the urine urgency-frequency symptom, hematuria, lumbago etc.
3.2. anus digital examination: be divided into I ° (egg is big) according to the prostate size, II ° (Ovum Anas domestica is big), III ° (goose egg is big).
3.3. lab testing comprises hemogram, and renal function (Bun, Cr).
3.4.B super prostate size and the residual urine volume measured.
3.5. side reaction is observed: symptom of digestive tract and distending pain of the breast reaction.
3.6. the drug withdrawal analysis of causes.
4. statistical method:
Observed result is pressed statistical method and is handled: (1) paired data t check; (2) sample average difference t check; (3) sign test etc.;
Two, result
1. clinical symptoms:
The nocturia number of times reduces to 2.47 ± 1.45 times for 4.63 ± 4.30 times before the medicine, and constant 9 examples before and after the medication of urine range are improved 15 examples, significantly improve 2 examples; Daytime the frequent micturition situation, medication preceding 6.29 ± 3.71 reduces to 4.47 ± 1.74 times, the urgent micturition phenomenon is removed 2 exceptions all improvement.4 routine hematurias are arranged before the medication, and hematuria disappears after the medication, and preceding 12 examples of medication have the soreness of waist wherein to still have the lumbago except that 4 examples bitterly, other 8 routine lumbago disappeared (table 2)
Clinicing symptom observation before and after table 2 medication (X ± SD)
| Clinical symptoms | Example number (n) | Before the medication | After the medication | The P value |
| Nocturia number of times (inferior) | 12 (NO.1) 14 (NO.1) 26 (always) | ??3.375±1.7467 ??5.7143±5.5077 ??4.6346±4.3048 | ??2.3583±0.7416 ??2.5714±1.8898 ??2.4731±1.4529 | ??＜0.05 ??＜0.01 ??＜0.01 |
| Frequent micturition number of times on daytime (inferior) | 12 (NO.1) 14 (NO.2) 26 (always) | ??5.3333±2.5614 ??7.1071±4.4036 ??6.2885±3.7126 | ??4.4167±1.8688 ??4.5143±1.6947 ??4.4693±1.7414 | ??＜0.05 ??＜0.01 ??＜0.05 |
| Dysuria degree (example) | Light in heavy | ????10 ????7 ????9 | ????1 ????9 ????16 |
2. prostatic stereomutation:
Anus inspection is checked, prostate hyperplasia III ° of 9 examples before the medication, and II ° of 11 examples, I ° of 6 examples, after medication February there be not outside the significant change volume 12 examples, and 14 examples of surplusing reduce I °-II ° (wherein 1 example reduces II °) respectively.Measure the prostate size with B ultrasonic, 19 routine volume-diminished, 7 examples change little.Wherein use the preceding average prostate volume 71.29-38.50cm of medicine No. 1
3, medication drops to 57.5g ± 26.79cm after February
3, with on average dropping to 54.59 ± 36.15 after prostate volume 81.29 ± 61.89 medications before No. 2 medicines.P value＜0.05.(seeing Table 3, table 4)
The big or small comparison of B-mode ultrasound tomography mensuration prostate before and after table 3 medication (X ± SD)
After treating before the treatment of example number
n＝12(No.1)????????71.2867±38.5014????57.5925±26.7938
n＝14(No.1)?????81.2879±61.8866??????52.0214±43.4780
N=26 (always) 76.6719 ± 51.6688 54.5927 ± 36.1507
Prostate volume obviously dwindled after analysis result showed medication, and is existing to statistics result (26 example) t=2.5177＞t0.05=2.060.There is significant difference P＜0.05.
Blood leukocytes density before and after table 4 medication, renal function Bun, the Cr comparison (X ± SD)
After treating before the project treatment
Blood WBC density 6738.46 ± 30717.78 6457.69 ± 2185.44
Bun?????????????15.5±9.29????????????14.02±10.54
Cr??????????????0.98±0.73????????????0.94±0.80
3. still do not have residual urine after no residual urine person took medicine before residual urine volume, B ultrasonic were measured 10 examples and taken medicine, have 3 routine residual urines slightly to increase in addition in 16 examples to surplus 13 routine residual urines obviously to reduce (seeing Table 5) outward
After the preceding medication of residual urine medication
0 11 examples, 12 examples
＜60m l4 example 9 examples
61-100ml 6 examples 3 examples
＞100ml 5 examples 2 examples
4. the side reaction of medicine:
One property crossed dizziness appears in 2 example companion's diarrhoea (No. 1 medicine), 2 examples, and myasthenia of limbs companion edema of lower limbs appears in 1 example, and the distending pain of the breast phenomenon appears in 5 examples.
5. the drug withdrawal analysis of causes:
Drug withdrawal midway, 5 examples, wherein 2 examples are owing to suffer from diarrhoea (No. 1 medicine), and 2 examples are owing to the property a crossed dizziness (No. 1 medicine), and 1 example is because of poor effect (No. 2 medicines).Side reaction disappears after the drug withdrawal.
Adopt the anal medication, it is contiguous not only can to reduce medicine side reaction but also agents area and body of prostate, local drug concentration is improved, be a kind of better route of administration, by clinical practice, two kinds of medicines are all obtained better effects, analysis shows, No. 2 better efficacy of the precious bolt in prostatitis, light to blocking degree especially, and be to be worth a kind of medicine of selecting with the prostate hyperplasia that infects.
The observation on Clinical Application of the suppository of hydrochloric prazosin of the present invention (No. 2, the precious bolt in prostatitis) treatment prostatic hyperplasia is as follows by Rui Jin, Shanghai hospital result of the test:
One, data and method
1. this organizes 26 examples " prostatic hyperplasia " patient all has urinating of June to 10 year to hesitate, urinate that stream slows down and the clinical symptoms of frequent micturition.The refusal operative treatment.Get rid of " neuronal bladder " simultaneously and reach " urethral stricture " pathological changes (seeing Table 6).
Table 6
| Age (on average) (year) | The course of disease (on average) (year) | Nocturia number of times (on average) (inferior/night) | Prostate footpath (on average) mm | |||
| NO 1Organize 13 examples | ??60-85(69.5) | 0.6-10(3.9) | ????2-6(4) | ??42-60(52) | ||
| NO 2Organize 13 examples | ??59-84(70.8) | 0.8-10(3.8) | ????2-6(4.1) | ??42-60(51.3) | ||
| Residual urine (on average) ml | A small amount of surplus urine (example) | Acute urinary retention (example) | ||||
| NO 1Organize 13 examples | ??70-260(121.3) | ???????1 | ????????????4 | |||
| NO 2Organize 13 examples | ??30-340(112.4) | ???????3 | ????????????2 | |||
2. medicinal application and detection method
Inactive used in the past any treatment prostatic hyperplasia medicine.Adopt morning, late internal rectum respectively to fill in one piece of suppository, the flat at least bed activity that recurred in 20 minutes of sleeping after the medication.If any giddy and blood pressure drops, change into and fill in anus or further decrement application one of night.SM February, check B ultrasonic and urine flow rate, acute urinary retention person medication was pulled out catheter in 5-7 days, B ultrasonic check after 3 days behind the tube drawing, routine blood test, blood liver function, Cr Bu, cholesterol before and after the medication, three esters, Electrocardioscopy.
Two, result
1. to the influence of clinical symptoms: after general medication next day to the week promptly the sense situation of urinating obviously improve February after the medication, NO
1Group is by average nocturia 4 times to 1.8 times, NO
2Average 4.1 times to 2.3 times of the nocturia of group before by medication, bladder residual urine NO
1Average 121.3ml average 74.5ml after the medication before the group medication, 4 routine residual urines wherein are by 70-110ml → 0.NO
2To the average 55.9ml in treatment back, wherein 3 routine residual urines are by 30ml to 0 by the preceding average 112.4ml of treatment for the surplus urine of group bladder.
2. medicine is to the influence of prostate size
Table 7
| (on average) mm before the transverse diameter treatment | Treatment back (on average) mm | |
| NO 1Group (13 example) | 42-63(52mm) | 40-60(48.8mm) |
| NO 2Group (13 example) | 42-62(51.3mm) | 41-74(48.6mm) |
B ultrasonic NO
1The group transverse diameter dwindles above 1cm person's 2 examples and accounts for 15.4%.
NO
2The group transverse diameter dwindles above 1cm person's 3 examples and accounts for 23.1%.
3. to the influence of urine flow rate
| ?????????????????NO 1Group (8 example) | ????????????????NO 2Group (9 example) | |||
| Before the treatment (on average) | Treatment back (on average) | Before the treatment (on average) | Treatment back (on average) | |
| (ml/ second) Qmax | 3.3-20.0(11.7) | 10.5-22.8(17.0) | 2.4-22.8(12.0) | 3.8-18.5(12.0) |
| (ml/ second) AFR | 2.0-8.6(5.1) | 5.3-13.2(10.0) | 1.0-8.5(4.6) | 1.0-11.2(6.5) |
4.NO
1Group and NO
2Group is to patient's blood Rt, liver function, and Cr Bun cholesterol, three esters, electrocardiogram does not have influence.
Three, discuss
1. this group is long-term prescription, and expectant treatment is reluctant patient with operation.After the medication in the past of stopping using was changed to " the precious bolt in prostatitis ", the patient promptly felt unobstructed micturition, to 6 acute urinary retention and retention catheterization person medication 5-7 days, pull out catheter after 3 examples effectively.(residual urine＜50ml) 2 example parts are effective, and 1 example is invalid.According to following treatment standard, it is as follows to list " the precious bolt in prostatitis " curative effect:
(1) produce effects: symptom is clearly better, and residual urine disappears; The urine flow rate is near normal.
(2) effective: symptom takes a turn for the better, and residual urine reduces by half; The urine flow rate improves 50%.
(3) part is effectively: symptom takes a turn for the better, the residual urine no change, and the urine flow rate is improved or no change slightly.
(4) invalid: symptom and the remnants equal no change of flow rate of urinating.
" the precious bolt in prostatitis " NO
1, produce effects with effectively reach 92.3%, NO
2Produce effects with effectively reach 69.3%, this and this medical instrument has the blocker effect of alpha-adrenergic receptor, minimizing bladder outlet resistance.The auxilliary effect that adds Chinese medicine and prohormone makes the body of prostate atrophy.It is relevant to cause the urine flow rate to be improved, but NO
2No significant change before and after the treatment of group maximum flow rate remains further to be studied.
2. pay effect
2.1. hypotension NO
1Organize 3 examples, NO
1Organize 5 examples, obvious hypotension, giddy are arranged after the medication, uncomfortable in chestly go out example and change 1 anus plug every night into, dizzy transference cure, but can play a medicine dual-purpose effect to original hyperpietic.
2.2. distending pain of the breast: NO
1Organize 3 examples.Symptom sand disappears after drug withdrawal or the decrement.
2.3. times of defecation increases, every day 2-4 time, NO1 organizes 4 examples.
3. " prostatitis precious bolt " clinical practice is to improving symptom, and reducing residual urine has positive effect, during the medication to hepatic and renal function, routine blood test, cholesterol and three esters, electrocardiogram does not have influence, but influence accounts for 53.8% to blood pressure, will in time adjust consumption to obvious hypotensive is arranged after the medication.Drug effect can be kept about 2 weeks after one course of treatment, and symptom has answer trend after the drug withdrawal, the suggestion maintenance dose.
The using method of the precious suppository in prostatitis of the present invention is as follows:
(1) initial dose: use the precious bolt bed in half piece of prostatitis to fill in anus just before going to bed and get final product, observation has or not " first-dose reaction " syndrome, and a few patients postural hypotension occurs with the precious bolt in prostatitis for the first time, dizzy cardiopalmus, perspiration even serious collapse.Lie up and to recover normal.As reactionless, then after 4-6 hour or gave 1 piece of prostatitis precious suppository amount in second day.The urine retention symptom is removed, and increases urinary volume.
(2) use the back through initial dose: after having " first-dose reaction " person to use 1-3 days the precious bolt in half piece of prostatitis, just can be by 1 piece of prostatitis treasured bolt use.State of an illness the lighter uses 1 piece just before going to bed: the heavier person of the state of an illness early, evening, respectively 1 piece of precious thromboembolism in prostatitis was gone into anus, and general one month is a course of treatment, takes the circumstances into consideration one week of drug withdrawal, begins for second course of treatment again.State of an illness symptom has clear improvement, and exempts operating on the misery of operation.
Use taboo:
(1) the prostate hyperplasia patient of patients with prostate cancer and essential operative treatment is forbidden prostatitis treasured bolt, because Drug therapy can not replace operative treatment.
(2) all have the allergy sufferers taboo to use to this product.
The pharmacokinetics result of the precious suppository in prostatitis of the present invention is:
The precious bolt in prostatitis used back blood drug level to reach peak value in 0.5-1 hour, and plasma half life is 2-3 hour, plasma protein tuberculosis rate height.Animals and human beings studies show that this product in a large number by metabolism, is mainly demethylation and conjugate, most of with bile and excrement drainage.
Another object of the present invention has provided the preparation method of the suppository (No. 2, the precious bolt in prostatitis) of hydrochloric prazosin, and this method comprises the following steps:
(1) gets the principal agent minipress and in rustless steel pulverizing machine, be ground into fine powder, cross 200 mesh sieves, be kept in the airtight light resistant container;
(2) with semi-synthetic fruit of cubeb litsea tree oil ester #36, drop in the jacketed pan steam heated 85-95 ℃, until whole thawings, standby;
(3) make the transition: get minipress and put in the beaker, add propylene glycol [1,2] and citric acid, the manual stirring is converted into liquid citric acid prazosin until minipress, and 70 ℃ of heating of water-bath in case of necessity get mixture 1; Add again the surfactant tween 80 stir evenly mixture 2, be heated to 95 ℃;
(4) emulsifying: get Arlacel-60 and mix with laurocapram, add the grey grease in semi-synthetic mountain of a small amount of thawing, mechanical agitation gets mixture 3, is heated to 95 ℃.Other gets mixture 2, add vigorous stirring in the mixture 3 with a small amount of multiple gradual, 95 ℃-100 ℃ of temperature, get emulsion blends 4 after half an hour, with fused semi-synthetic fruit of cubeb litsea tree oil fat #36, rise progressively to getting mixture 5 in the principle adding mixture 4 simultaneously, stop heating with equivalent, continue stirring and drop to 36-37 ℃, in case of necessity logical cold water in the jacketed pan until fluid temperature;
(5) moulding: mixture 5 (36-43 ℃) is carried out moulding, in case of necessity coating liquid paraffin on the bolt mould;
(6) with aluminium alloy bolt mould, put into refrigerator, cooling is condensed and was solidified 40 minutes;
(7) arrangement: claim average piece of amount, chemically examine qualified back packing.
Suppository of the present invention has following characteristics:
(1) nearest apart from the prostate target organ, medicine concentration around prostata tissue is the highest.Overcome oral administration, route is long, and drug distribution concentration around prostata tissue is low, the shortcoming of weak curative effect.
(2) medicine circulates without body, without the detoxifcation tissue of digestive tract especially liver, so that side reaction and toxicity should be mutually is little.
(3) minipress, dissolubility is little in the body fluid, and bioavailability is low, and after changing citric acid into and being processed into the citric acid prazosin, dissolubility increases, the bioavailability height, curative effect obviously increases.
(4) substrate that to adopt semi-synthetic Fructus Litseae grease be suppository is discharged on the mucous membrane of rectum wall water soluble drug fast from suppository, reach quick-acting purposes.
(5) after medicine discharges in suppository, reach prostata tissue through fusing, diffusion, infiltration, wherein infiltration is difficult problem for a long time.This product is adopted laurocapram (azone) highly effective skin penetrating agent, and curative effect is multiplied, and reaches quick-acting purposes especially.
(6) be evenly dispersed in the fat-soluble substrate for increasing water soluble drug, add tween 80, the Arlacel-60 surfactant is made Emulsion with medicine emulsifying.
The specific embodiment
Embodiment 1
Get 1 in 250ml beaker, take by weighing 5g minipress fine powder, add 4g citric acid, 25g propylene glycol (1,2), in 70 ℃ of water-baths, heat, be stirred to liquefaction, add the 50g tween 80 then, stir, be heated to 95 ℃, get solution (I), have the beaker of the grey oils and fats #36 in the semi-synthetic mountain of 1400g in water-bath, to be incubated 85-95 ℃ claiming, be stirred to content and all melt, get solution (II).
Other gets 1 in 2000ml beaker, adds the 40g Arlacel-60, the tall and erect phenol of 60g Laurel nitrogen, add small volume of solution (II), be heated to 95 ℃, stir evenly, then with solution (I) at 95-100 ℃, under vigorous stirring, divide 5 times and add gradually, become emulsion after half an hour approximately, this moment, the solution (II) with remainder added gradually, stop heating, continue to stir, be cooled to 36-37 ℃ and can irritate mould, through the cooling, curing and demolding, just required suppository.
Embodiment 2
Every piece of content of the name of an article
1 minipress 3mg
2 citric acid 2.5mg
3 laurocapram 40mg
4 propylene glycol (1,2) 20mg
5 Tween 80 35mg
6 sodium laurylsulfate 8mg
7 sorbester p18 20mg
8 semi-synthetic litsea cubeba oil fat #26 1.4g
Theoretical every piece of weight 1.53 grams
Fusing point 33-35 ℃
Preparation manipulation is with embodiment 1.
Embodiment 3
Every piece of content of the name of an article
1 minipress 6mg
2 citric acid 5mg
3 laurocapram 80mg
4 propylene glycol (1,2) 40mg
5 Tween 80 70mg
6 sodium laurylsulfate 16mg
7 sorbester p18 40mg
8 semi-synthetic litsea cubeba oil fat #36 1.4g
Theoretical every piece of weight 1.65 grams
Fusing point 33-35 ℃
Preparation manipulation is with embodiment 1.
Embodiment 4
Every piece of content of the name of an article
1 minipress 8mg
2 citric acid 6mg
3 laurocapram 100mg
4 propylene glycol (1,2) 40mg
5 Tween 80 75mg
6 sodium laurylsulfate 16mg
7 sorbester p18 40mg
8 semi-synthetic litsea cubeba oil fat #36 1.4g
Theoretical every piece of weight 1.68 grams
Fusing point 33-35 ℃
Preparation manipulation is with embodiment 1.
Claims (3)
1. the suppository of a hydrochloric prazosin is characterized in that this suppository comprises following composition:
Sequence number The name of an article Every piece of content Per 10,000 pieces of content
????1 Minipress ????3.5-5.0mg ????35-50g
????2 Citric acid ????3mg ????30g
????3 Laurocapram ????40-60mg ????400-600g
????4 Propylene glycol (1,2) ????20mg ????200g
????5 Tween 80 ????38mg ????380g
????6 Sodium laurylsulfate ????8mg ????80g
????7 Sorbester p18 ????20mg ????200g
????8 Semi-synthetic Fructus Litseae oils and fats #36 ????1.40g ????14000g
Weigh for theoretical every piece ????1.53-1.56
Fusing point ????33-35℃
2. the preparation method of the suppository of a hydrochloric prazosin is characterized in that this method comprises the following steps:
(1) gets the principal agent minipress and in rustless steel pulverizing machine, be ground into fine powder, cross 200 mesh sieves, be kept in the airtight light resistant container;
(2) with semi-synthetic fruit of cubeb litsea tree oil ester #36, drop in the jacketed pan steam heated 85-95 ℃, until whole thawings, standby;
(3) make the transition: get minipress and put in the beaker, add propylene glycol [1,2] and citric acid, the manual stirring is converted into liquid citric acid prazosin until minipress, and 70 ℃ of heating of water-bath in case of necessity get mixture 1; Add again the surfactant tween 80 ℃ stir evenly mixture 2, be heated to 95 ℃;
(4) emulsifying: get Arlacel-60 and mix with laurocapram, the grey grease in semi-synthetic mountain that adds a small amount of thawing, mechanical agitation gets mixture 3, be heated to 95 ℃, other gets mixture 2, add vigorous stirring in the mixture 3 with a small amount of multiple gradual, 95 ℃-100 ℃ of temperature, get emulsion blends 4 after half an hour, with fused semi-synthetic fruit of cubeb litsea tree oil fat #36, rise progressively to getting mixture 5 in the principle adding mixture 4 simultaneously, stop heating with equivalent, continue to stir 36-37 ℃, in case of necessity logical cold water in the jacketed pan until fluid temperature decline;
(5) moulding: mixture 5 (36-43 ℃) is carried out moulding, in case of necessity coating liquid paraffin on the bolt mould;
(6) with aluminium alloy bolt mould, put into refrigerator, cooling is condensed and was solidified 40 minutes;
(7) arrangement: claim average piece of amount, chemically examine qualified back packing.
3. the application of the minipress chemical compound of a structural formula I in preparation treatment prostate hyperplasia disease drug
Formula I
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|---|---|---|---|
| CNB2004100184482A CN100393316C (en) | 2004-05-19 | 2004-05-19 | Suppository containing prazosin hydrochloride, its preparation method and application |
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| Publication Number | Publication Date |
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| CN1698615A true CN1698615A (en) | 2005-11-23 |
| CN100393316C CN100393316C (en) | 2008-06-11 |
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