CN101816749A - Medicament for curing dysuria, preparation method and quality control method thereof - Google Patents
Medicament for curing dysuria, preparation method and quality control method thereof Download PDFInfo
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Abstract
The invention discloses a medicament for curing dysuria, a preparation method and a quality control method thereof. The medicament is prepared by mainly using the following raw materials in part by weight: 240 to 360 parts of semen psoraleae, 360 to 560 parts of leonurus, 240 to 360 parts of spora lygodii and 180 to 300 parts of tulip bulb. In the quality control method, a plurality of medicinal materials in the product are controlled by an HPLD method and a TLC method. The medicament, the preparation method and the quality control method thereof have the advantage that: a clinical experiment shows that the effective rate of an experimental group is 98.85 percent and the effective rate of a control group is 96.92 percent. Due to dried powder directly used as medicament, the best concentration proportion and a specific drying condition, the process can be controlled better compared with the process of using clear paste as medicament.
Description
Technical field
The invention belongs to the field of Chinese medicines, relate to a kind of method for making for the treatment of medicine and this medicine thereof of the difficulty in urination, and method of quality control.
Background technology
Hyperplasia of prostate also claims prostate hyperplasia, is that a kind of prostate obviously increases and influences the commonly encountered diseases of elderly men health, and hyperplasia of prostate is a clinical characters with carrying out property frequent micturition, dysuria.Hyperplasia of prostate belongs to the category of Chinese medicine " difficulty in urination ", " smart infirmity ".The difficulty in urination is meant that urine amount is few, drop and going out, and very then urine is inaccessible obstructed, and wherein again with dysuria, drop is and short and small, and patient's condition comparatively slowly person is " infirmity "; With the obturation of urinating, drop is obstructed, and the more anxious person of patient's condition is called " closing ".
In recent years, China's population average life is increasing, and the old people is more and more, and the hyperplasia of prostate sickness rate has trend of rising gradually.Chinese medicine is used for the treatment of the difficulty in urination, multiple prescription is arranged in clinical, yet, the controllability of most prescriptions is also bad, and technological parameter is not complete, and then has influenced the performance of product curative effect, especially method of quality control is unreasonable, and the progressive diversity that has increased between medicine is criticized has influenced the stable of curative effect greatly.
Summary of the invention
The purpose of this invention is to provide that a kind of production technology is controlled, good effect, quality control treat medicine of the difficulty in urination and preparation method thereof easily.
The medicine of the treatment difficulty in urination of the present invention, it mainly is to be formed by the following weight parts feedstock production.
Fructus Psoraleae 240-360 part Herba Leonuri 360-560 part
Spora Lygodii 240-360 part Pseudobulbus Cremastrae Seu Pleiones 180-300 part.
The consumption of each raw material is in the medicine of the preferred treatment difficulty in urination:
480 parts of 300 parts of Herba Leonuris of Fructus Psoraleae
240 parts of 300 parts of Pseudobulbus Cremastrae Seu Pleioness of Spora Lygodii.
The invention provides manufacturing method for above mentioned medicine, it comprises the following steps:
Take by weighing described four Chinese medicine material, wherein Spora Lygodii is decocted a drug wrapped, and adds 8 times of water gaging steaming and decoctings twice at every turn, and 3 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrate decompression is concentrated into 60 ℃ of survey relative densities and is about 1.35 clear paste, at 60 ℃ of following vacuum dryings, gets dry extract.
" decoct a drug wrapped ": the medicine that has when being meant into decoction will bind up with gauze in addition into frying in shallow oil, and Spora Lygodii is because light weight, tiny easily floats on the soup surface, and the inventor decocts a drug wrapped it.
Preferably also have in the crude drug of treatment difficulty in urination medicine of the present invention: Herba Lysimachiae 240-360g, succinum 24-36g.
The consumption of each raw material in the medicine of further preferred the invention described above is:
300 parts of 480 portions of Herba Lysimachiaes of 300 parts of Herba Leonuris of Fructus Psoraleae
240 parts of 30 parts of Pseudobulbus Cremastrae Seu Pleioness of 300 parts of succinums of Spora Lygodii.
The preparation method that further preferably contains the medicine of 6 flavor medical materials is: take by weighing described Six-element medical material, Succinum powder is broken into fine powder, crosses 80 mesh sieves, and is standby; The five tastes such as all the other Fructus Psoraleaes, wherein Spora Lygodii is decocted a drug wrapped, and adds 8 times of water gaging steaming and decoctings twice at every turn, and 3 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrate decompression is concentrated into 60 ℃ of survey relative densities and is about 1.35 clear paste, at 60 ℃ of following vacuum dryings, gets dry extract.
The method of quality control of arbitrary medicine of the present invention, this method comprises assay:
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica, are mobile phase with methanol-0.02mol/L potassium dihydrogen phosphate aqueous solution 20-80: 20-80, and the detection wavelength is 246nm; Flow velocity: 1ml/min; Number of theoretical plate calculates by the psoralen peak should be not less than 3000;
The preparation of reference substance solution 24 hours the psoralen reference substance of phosphorus pentoxide vacuum drying of learning from else's experience is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.05mg, promptly;
Medicine of the present invention is got in the preparation of need testing solution, porphyrize, and precision takes by weighing about 2g in tool plug conical flask, the accurate water saturated n-butyl alcohol of 25ml that adds, claim decide weight, supersound process 30 minutes is put coldly, and weight decided in title again, supply the weight that subtracts mistake with water saturated n-butyl alcohol, filter, promptly;
Accurate respectively reference substance solution and each 10ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly;
The every preparation unit of this product contains Fructus Psoraleae with psoralen C
11H
6O
3Meter must not be less than 0.12mg.
In order to differentiate medicine of the present invention fast, also comprise one or more of following discriminating item in the method for quality control:
(1) get medicine of the present invention, porphyrize takes by weighing 3g, adds n-butyl alcohol 30ml supersound process 1 hour, puts coldly, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets psoralen, the isopsoralen reference substance, add mixed solution that methanol makes psoralen that every 1ml contains 0.5mg, 2mg isopsoralen product solution in contrast, according to the thin layer chromatography test of Chinese Pharmacopoeia, draw each 10 μ l of above-mentioned two kinds of solution, putting in the same carboxymethyl cellulose rope sodium that contains respectively is on the silica gel g thin-layer plate of adhesive, with normal hexane-ethyl acetate of 7: 3 was developing solvent, launch, take out, dry; Put under the 254nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show two identical fluorescence speckles;
(2) get medicine of the present invention, porphyrize takes by weighing 2g, adds ethanol 30ml, supersound extraction 20 minutes, filter, filtrate is concentrated into about 5ml, is added on active carbon-alumina column of having handled well active carbon 0.6g wherein, 60-80 order, neutral alumina 2g, 100-200 order, mixing, dress post, column internal diameter 10mm; With ethanol 30ml eluting, collect eluent, evaporate to dryness, residue adds 6 → 1000 hydrochloric acid solution 2ml dissolving, filters, and filtrate is put to steam in the water-bath near and done, residue adds ethanol 0.5ml makes dissolving as need testing solution, other gets the stachydrine hydrochloride reference substance, adds ethanol and makes the solution that every 1ml contains 5mg, in contrast product solution.According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with n-butyl alcohol-hydrochloric acid of 12: 4.5: 1.5-ethyl acetate, launch, take out, to dry, spray is with rare bismuth potassium iodide test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Optimum dosage form of the present invention is for making coated tablet, and the preparation method of this coated tablet is: take by weighing described Six-element medical material, Succinum powder is broken into fine powder, crosses 80 mesh sieves, and is standby; The five tastes such as all the other Fructus Psoraleaes, wherein Spora Lygodii is decocted a drug wrapped, and adds 8 times of water gaging steaming and decoctings twice at every turn, and 3 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrate decompression is concentrated into 60 ℃ of survey relative densities and is about 1.35 clear paste, at 60 ℃ of following vacuum dryings, get dry extract, the dried cream powder that makes is broken, cross 80 mesh sieves, add described succinum fine powder and appropriate amount of starch, mixing, alcohol granulation with 80% is crossed 18 mesh sieves, and is dry down at 60 ℃, cross 18 mesh sieve granulate, add an amount of microcrystalline Cellulose and 0.1% magnesium stearate, be pressed into 1000, sugar coating promptly gets coated tablet.
The method of quality control of above-mentioned coated tablet comprises:
Differentiate:
(1) it is an amount of to get this product, remove sugar-coat after, porphyrize takes by weighing 3g, adds n-butyl alcohol 30ml supersound process 1 hour, puts coldly, filters, filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets psoralen, the isopsoralen reference substance, add mixed solution that methanol makes psoralen that every 1ml contains 0.5mg, 2mg isopsoralen product solution in contrast, according to the thin layer chromatography test of Chinese Pharmacopoeia, draw each 10 μ l of above-mentioned two kinds of solution, putting in the same carboxymethyl cellulose rope sodium that contains respectively is on the silica gel g thin-layer plate of adhesive, with normal hexane-ethyl acetate of 7: 3 was developing solvent, launch, take out, dry; Put under the 254nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show two identical fluorescence speckles;
The Rf value that this method is differentiated is better than the thin layer chromatography condition of other developing solvents at 365nm greater than 0.4.
(2) it is an amount of to get this product, remove coating after, porphyrize, take by weighing 2g, add ethanol 30ml, supersound extraction 20 minutes, filter, filtrate is concentrated into about 5ml, is added on active carbon-alumina column of having handled well, active carbon 0.6g wherein, 60-80 order, neutral alumina 2g, the 100-200 order, mixing, dress post, column internal diameter 10mm; With ethanol 30ml eluting, collect eluent, evaporate to dryness, residue adds 6 → 1000 hydrochloric acid solution 2ml dissolving, filters, and filtrate is put to steam in the water-bath near and done, residue adds ethanol 0.5ml makes dissolving as need testing solution, other gets the stachydrine hydrochloride reference substance, adds ethanol and makes the solution that every 1ml contains 5mg, in contrast product solution.According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with n-butyl alcohol-hydrochloric acid of 12: 4.5: 1.5-ethyl acetate, launch, take out, to dry, spray is with rare bismuth potassium iodide test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
Assay:
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica, are at 45: 55 mobile phase with methanol-0.02mol/L potassium dihydrogen phosphate aqueous solution, and the detection wavelength is 246nm; Flow velocity: 1ml/min; Number of theoretical plate calculates by the psoralen peak should be not less than 3000;
The preparation of reference substance solution 24 hours the psoralen reference substance of phosphorus pentoxide vacuum drying of learning from else's experience is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.05mg, promptly;
20 of this product are got in the preparation of need testing solution, remove sugar-coat, porphyrize, and precision takes by weighing about 2g in tool plug conical flask, the accurate water saturated n-butyl alcohol of 25ml that adds claims to decide weight, and supersound process 30 minutes is put cold, claim again to decide weight, supply the weight that subtracts mistake, filter, promptly with water saturated n-butyl alcohol; Accurate respectively reference substance solution and each 10ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly;
Every of this product contains Fructus Psoraleae with psoralen C
11H
6O
3Meter must not be less than 0.12mg.
The used crude drug source of the present invention is as follows:
Fructus Psoraleae is the dry mature fruit of legumes psoraleae Psoralea corylifolia L..
Herba Leonuri is the fresh or dry aerial parts of labiate Herba Leonuri Leonurus japonicus Houtt..
Herba Lysimachiae is the dry herb of Primulaceae plant Lysimachia christinae Hance Lysimachia christinae Hance.
Spora Lygodii is the drying and ripening robe of Lygodiaceae plant Spora Lygodii Lygodium japonicum (Thunb.) Sw..
Succinum Succinum is the resin of Pinaceae pine genus plant in ancient times, is embedded in the fossil sample material that forms for a long time in stratum year.After digging out, remove impurity.
Pseudobulbus Cremastrae Seu Pleiones is the dry pseudobulb of blue Cremastra appendiculata (D.Don) Makino of orchid Du Juan, pleione bulbocodioides Pleione bulbocodioides (Franch.) Rolfe or Yunnan pleione bulbocodioides Pleioneyunnanensis Role.
Beneficial effect of the present invention is, clinical trial shows that the effective percentage of taking the test group of sample of the present invention is 98.85%, and the effective percentage of matched group is 96.92%.Because employing dry powder (rather than clear paste) directly is used as medicine and has provided best spissated proportion, concrete drying condition, thereby is used as medicine and uncertain concentrated proportion and drying condition with respect to clear paste, technology is more controlled.
The test of test example 1 process controllability
Through preferred repeatedly, the decocting liquid that will make by extraction process filters, and filtrate decompression is concentrated into the clear paste that relative density is 1.35 (60 ℃ of surveys), and this moment, clear paste moisture was less, helped drying.
Through preferred, find that vacuum drying drying time is the shortest, baking temperature is controlled at about 60 ℃, and vacuum should be controlled at-and below the 0.08MPa, the gained dry product is loose frangible.
Through a large amount of screenings, according to the physical characteristic of material forming, grope the best particulate homogeneity and the condition of tablet weight variation, take into account its compressibility and disintegration simultaneously, obtain the classification and the consumption thereof of following adjuvant.
The research of the moulding process of table 1 preparation
| Tested number | Dried cream powder (g) | Succinum powder (g) | Starch (g) | Microcrystalline cellulose (g) | Binder dosage (ml) | Magnesium stearate (g) |
| ??1 | ??22.8 | ??2.9 | ??- | ??- | 70% ethanol 15ml | |
| ??2 | ??22.8 | ??2.9 | ??2.0 | ??- | 70% ethanol 15ml | |
| ??3 | ??22.8 | ??2.9 | ??4.0 | ??- | 80% ethanol 15ml | |
| ??4 | ??22.8 | ??2.9 | ??4.0 | ??0.6 | 80% ethanol 15ml | ??0.03 |
Investigate the plain tablet quality of gained by following index.
Table 2 prescription performance evaluation
| Prescription | Granulate and the tabletting situation | Mobility of particle (angle of repose) | Hardness (kg) | Disintegration time (min) |
| |
Soft material is more sticking, is difficult to granulate | - | ||
| |
Soft material is more sticking, is difficult to granulate | - | ||
| |
The soft material viscosity is suitable, can fine granulation.But the slice, thin piece disintegration time of compacting gained is long slightly | ＞40 | ～3.4 | 37 |
| Prescription | Granulate and the tabletting situation | Mobility of particle (angle of repose) | Hardness (kg) | Disintegration time (min) |
| |
The soft material viscosity is suitable, can fine granulation.Mobility of particle is also better | ＜40 | ～4.2 | 24 |
Conclusion: comprehensive above research, the 4 granulation situations of writing out a prescription as can be seen are better, can fine granulations, the gained granule can flow into nib smoothly, and the hardness of the slice, thin piece that makes, disintegration time are all comparatively desirable.
Test example 2 content assaying methods of the present invention are learned and are investigated
1, the selection of mobile phase
Preferred multiple mobile phase conditional effect is all undesirable, and such as adopting methanol: water (60: 40) is mobile phase, and the psoralen peak does not reach fully with other compositions and separates as a result; Be, use methanol-0.02mol/L potassium dihydrogen phosphate aqueous solution (45: 55) instead and be mobile phase that psoralen and other components all reach baseline separation unexpectedly, theoretical cam curve is 4891.
Chromatographic column is in the test: SHIMADZU, OP-ODS, 5um.
2, extract choice of Solvent
Through a large amount of screenings, chosen optimum solvent.Have the The selection result of representative as follows:
It is an amount of to get test sample, porphyrize, precision takes by weighing 2 parts, every part of about 2g:(1) and methanol 25ml, supersound extraction 30 minutes; (2) water saturated n-butyl alcohol 25ml, supersound extraction 30 minutes.
Each sample introduction 10ul of above-mentioned sample solution the results are shown in Table 3:
Table 3 extracts choice of Solvent
Best and the glitch-free water-saturated n-butanol of selective extraction effect is as extracting solvent.
3, the preparation of negative control solution and disturbed condition
Take by weighing all the other flavour of a drug except that Fructus Psoraleae in the prescription ratio, make the negative sample that lacks Fructus Psoraleae, make the negative control solution that lacks Fructus Psoraleae by above-mentioned test sample preparation method by preparation technology.Measurement result shows: do not have obvious impurity at retention time place, corresponding psoralen peak and disturb.
4, linear relationship is investigated
Getting concentration is 0.49mg/ml psoralen reference substance solution, precision measures 0.25,0.50,1.0,1.25 respectively, 1.50ml is in the 10ml measuring bottle, add methanol respectively and be diluted to scale, shake up, promptly get the psoralen reference substance solution of following concentration, difference sample introduction 10ul, measuring by the chromatographic condition of drafting, is vertical coordinate with the peak area integrated value, and psoralen amount (ng) is an abscissa drawing standard curve, calculate regression equation: y=4000000x-16180, r=0.9997
Table 4 linear relationship is investigated
Test shows that the psoralen sample size is good linear relationship in the 0.1225-0.7350ug scope.
5, precision test
Get need testing solution, continuous sample introduction 6 times, the peak area of mensuration psoralen calculates relative standard deviation, and RSD% is 0.64%.
6, stability test is placed need testing solution under room temperature, measures the peak area of record psoralen, the stability of investigation sample solution, calculating relative standard deviation respectively at the 0th, 2,4,6,8 hour.
The result shows, at room temperature places, and measures in 8 hours and stablizes, and RSD% is 0.42%.
7, replica test
It is an amount of to get test sample, the desaccharide clothing, and porphyrize, precision takes by weighing 5 parts, measures the peak area of psoralen, calculates relative standard deviation, and RSD% is 1.15%.
8, the response rate
Adopt the application of sample absorption method, get test sample (content of known psoralen), the desaccharide clothing, porphyrize, precision takes by weighing 6 parts, adds 0.5mg/ml psoralen reference substance solution 1ml respectively, makes test sample.Be calculated as follows the response rate.
Response rate %=(psoralen amount in actual measurement psoralen amount-sample)/interpolation psoralen amount * 100%.
As a result, average recovery rate is 97.68%, RSD% is 1.00%.
Test example 3: clinical trial
According to the clinical research guideline of new Chinese medicine to chemicotherapy attenuation and/or potentiation.
One, case is selected
(1) diagnostic criteria
1, traditional Chinese medical science sign diagnostic criteria
(1) urine meaning is anxious frequently, firmly urinate repeatedly, but difficulty in urination goes out, and drop is smooth or inaccessible obstructed;
(2) swollen full, the distending pain of lower abdomen;
(3) though the difficulty of urinating is not accompanied Urethra astringent pain;
(4) on inspection, bladder has remaining urine.
2. Chinese medical discrimination
Syndrome of dampness-heat of bladder
Urine amount is few, drop and descend, or urine retention is obstructed, and lower abdomen overflow, bitter taste mouth glue, or feeling thirst but no desire to drink, red tongue, yellowish fur, rapid pulse.
Lung-heat is stopped up the Sheng card
Little volume drop is not well, or tiny drop is obstructed, tired thist with desire to drink, and short of breath, or cough is arranged, tongue fur BOHUANG, rapid pulse.
Liver depression and Qi stagnation
Urinary obstruction, or logical and not smooth, depressed emotion, or be tired of susceptible to get angry, flank distension, red tongue, thin lingual fur or BOHUANG, stringy pulse more.
Urinary tract becomes silted up and hinders disease
Under the urine drop difficulty, lower abdomen distension pain, purplish tongue, or petechia is arranged, hesitant pulse.
The deficiency of QI in middle-JIAO card
Sagging distention in the smaller abdomen, the time desire urine and not drawing, or amount is smooth less and not, spirit is tired, inappetence is breathed hard and language is low thin, pale tongue, thin fur, weak pulse.
Syndrome of deficiency of both qi and yin
Urine drop and descend, unable discharge, tired, xerostomia dysphoria with smothery sensation, red tongue, tongue less, thready and rapid pulse.
Kidney yang is lost deficiency syndrome
Little volume drop is not well, and very then drop does not go out, and discharges unablely, and Mian Se Koushi is white, timid and weak mind, and fear of cold, waist is dreary and aching and limp unable, pale tongue, tongue is white, deep-thready pulse and late.
3. disease weight grade scale
Calculate iterated integral (seeing attached list 5) by following point system, with what of integration as state of an illness weight grade scale.
Table 5 disease weight grade scale
| Symptom and sign | 0 |
1 |
2 |
3 minutes |
| Dysuria | Normally | Urine thin is wire | The interrupted one-tenth of urine stream line | Urine flows tiny drop and does not become line down |
| The lower abdomen symptom | Asymptomatic | Full vexed sense | Expand, expire | Expand, full, bitterly |
| Urination time | ＜40 seconds | 40-50 second | 51-60 second | ＞60 seconds |
| Urine stream is anxious | ＞15ml/ second | 11-15ml/ second | 6-10ml/ second | ＜6ml/ second |
| Residual urine amount | ??＜10ml | ??10-50ml | ??51-100ml | ??＞100ml |
Slightly≤7 minute, moderate 8-10 branch, severe 〉=11 minute.
(2) include standard in
Meet primary disease diagnosis and Chinese medical discrimination standard person, can include the test case in.
(3) exclusion standard
(1) because of lithangiuria, tumor, oliguria or anuria due to the acute and chronic renal failure.
(2) stranguria.
(3) age is at under-18s or over-65s, to this medicine allergy sufferers.
(4) be associated with serious primary disease such as cardiovascular, liver and hemopoietic system, psychotic.
(5) the anti-standard of including in that do not meet, not medication in accordance with regulations can't be judged that curative effect or data are not congruent to affect the treatment or safety judgement person.
Two, observation index
(1) safety is observed
(1) general health check-up project.
(2) blood, urine, just routine examination.
(3) heart, liver, kidney function test.
(2) curative effect observation
1, symptom (heating, the unobstructed situation of urinating, total volume of urine, urine color, matter, lower abdomen sensation, waist lacquer sensation, the mental status, the symptom of spleen and stomach, cardiopalmus, dyspnea with rapid and short breath etc.).
2, sign (body temperature, pulse are breathed, blood pressure, complexion, few attached tenderness, the kidney district kowtows pain, bladder is kowtowed turbid, the ureter tenderness, edema, anus refers to inspection situation, picture of the tongue, pulse condition).
3, blood, routine urianlysis.
4 livers, kidney function test.
5 kidneys, bladder, prostate ultrasound diagnosis.
Three, curative effect determinate standard
1, clinic control: cardinal symptom and sign disappear, and integration reduces more than 90%, and it is normal that physical and chemical index recovers.
2, produce effects: cardinal symptom and sign are most of to disappear, and integration reduces 60-89%, and physical and chemical index is normal substantially.
3, effective: cardinal symptom and sign partly alleviate or disappear, and integration reduces 15-59%, and physical and chemical index takes a turn for the better to some extent.
4, invalid: cardinal symptom and sign no change, even increase the weight of.
Four, the Therapeutic Method test group is oral, one time 3,2 times on the one.2 weeks were a course of treatment.Matched group capsule for treating urination difficulty (Squama Manis, Cortex Cinnamomi).
Five, result of the test
Table 6 liang group physical data relatively
Table 7 liang group therapeutic effect of syndrome relatively
The primary symptom integration changes relatively before and after table 8 treatment
Change of illness state relatively before and after table 9 treatment
Description of drawings
Fig. 1, psoralen sample HPLC liquid chromatogram;
Fig. 2, psoralen reference substance HPLC liquid chromatogram;
Stachydrine hydrochloride TLC thin-layer chromatogram in Fig. 3, the Herba Leonuri;
1 is the stachydrine hydrochloride reference substance among the figure; 2-4 is a sample of the present invention;
The TLC thin-layer chromatogram of psoralen and isopsoralen in Fig. 4, the Fructus Psoraleae;
1 is psoralen, isopsoralen reference substance among the figure; 2-4 is a sample of the present invention.
The specific embodiment
480 parts of 300 parts of Herba Leonuris of Fructus Psoraleae
240 parts of 300 parts of Pseudobulbus Cremastrae Seu Pleioness of Spora Lygodii
Take by weighing above medical material, wherein Spora Lygodii is decocted a drug wrapped, and adds 8 times of water gaging steaming and decoctings twice at every turn, and 3 hours for the first time, 1 hour for the second time.Collecting decoction filters, and filtrate decompression is concentrated into the clear paste that relative density is about 1.35 (60 ℃ of surveys), and vacuum drying (60 ℃) gets dry extract.Pulverize, sieve (crossing 80 mesh sieves) adds appropriate amount of starch, mixing, and the alcohol granulation with 80% (18 mesh sieve), dry (60 ℃), granulate (18 mesh sieve) adds an amount of microcrystalline Cellulose and 0.1% magnesium stearate, is pressed into 1000, promptly.
300 parts of 480 portions of Herba Lysimachiaes of 300 parts of Herba Leonuris of Fructus Psoraleae
240 parts of 30 parts of Pseudobulbus Cremastrae Seu Pleioness of 300 parts of succinums of Spora Lygodii
Take by weighing described Six-element medical material, Succinum powder is broken into fine powder, crosses 80 mesh sieves, and is standby; The five tastes such as all the other Fructus Psoraleaes, wherein Spora Lygodii is decocted a drug wrapped, and adds 8 times of water gaging steaming and decoctings twice at every turn, and 3 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrate decompression is concentrated into the clear paste that relative density is about 1.35 (60 ℃ of surveys), and vacuum drying (60 ℃) gets dry extract.Pulverize, sieve (crossing 80 mesh sieves) adds described succinum fine powder and appropriate amount of starch, mixing, alcohol granulation with 80% (18 mesh sieve), dry (60 ℃), granulate (18 mesh sieve), add an amount of microcrystalline Cellulose and 0.1% magnesium stearate, be pressed into 1000, promptly.
Embodiment 3-7
The medical material kind of embodiment 3-5 and make preparation with embodiment 1, the medical material kind of embodiment 6-7 and make preparation with embodiment 2
Table 10 embodiment 3-7
| |
|
Embodiment 5 | Embodiment 6 | |
|
| Fructus Psoraleae | ??260 | ??340 | ??300 | ??320 | ??260 |
| Herba Leonuri | ??380 | ??540 | ??500 | ??480 | ??450 |
| Herba Lysimachiae | ??240 | ??360 | |||
| Spora Lygodii | ??280 | ??340 | ??260 | ??340 | ??300 |
| Succinum | ??24 | ??36 | |||
| Pseudobulbus Cremastrae Seu Pleiones | ??200 | ??280 | ??240 | ??260 | ??280 |
| Actual production (sheet) | ??952 | ??971 | ??905 | ??912 | ??919 |
| Unit substrate weight (g/ sheet) | ??0.3 | ??0.3 | ??0.3 | ??0.3 | ??0.3 |
| Psoralen amount (mg/ sheet) | ??0.21 | ??0.22 | ??0.17 | ??0.19 | ??0.24 |
The discriminating of embodiment 9 coated tablet quality standards of the present invention
It is an amount of that this product is got in [discriminating] (1), remove sugar-coat after, porphyrize takes by weighing 3g, adds n-butyl alcohol 30ml supersound process 1 hour, puts coldly, filters, filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets psoralen, the isopsoralen reference substance, add mixed solution that methanol makes psoralen that every 1ml contains 0.5mg, 2mg isopsoralen product solution in contrast, according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia nineteen ninety-five version) test, draw each 10 μ l of above-mentioned two kinds of solution, putting in the same carboxymethyl cellulose rope sodium that contains respectively is on the silica gel g thin-layer plate of adhesive, with normal hexane-ethyl acetate (7: 3) is developing solvent, launch, take out, dry.Put under the ultra-violet lamp (254nm) and inspect.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show two identical fluorescence speckles.
(2) it is an amount of to get this product, remove coating after, porphyrize, take by weighing 2g, add ethanol 30ml, supersound extraction 20 minutes. filter, filtrate is concentrated into about 5ml, is added on active carbon-alumina column (active carbon 0.6g, the 60-80 order handled well, neutral alumina 100-200 order, 2g, mixing, the dress post, column internal diameter 10mm) on,, collects eluent with ethanol 30ml eluting, evaporate to dryness, residue adds (6 → 1000) hydrochloric acid solution 2ml dissolving, filters, and filtrate is put to steam in the water-bath near and done, residue adds ethanol 0.5ml makes dissolving as need testing solution, other gets the stachydrine hydrochloride reference substance, adds ethanol and makes the solution that every 1ml contains 5mg, in contrast product solution.According to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia nineteen ninety-five version) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with n-butyl alcohol-hydrochloric acid-ethyl acetate (12: 4.5: 1.5) is developing solvent, launches, and takes out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
[assay] measured according to high performance liquid chromatography (appendix of Chinese Pharmacopoeia).
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica, are mobile phase with methanol-0.02mol/L potassium dihydrogen phosphate aqueous solution (45: 55), and the detection wavelength is 246nm; Flow velocity: 1ml/min; Number of theoretical plate calculates by the psoralen peak should be not less than 3000.
The preparation of reference substance solution 24 hours the psoralen reference substance of phosphorus pentoxide vacuum drying of learning from else's experience is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.05mg, promptly.
20 of this product are got in the preparation of need testing solution, remove sugar-coat, porphyrize, and precision takes by weighing about 2g in tool plug conical flask, the accurate water saturated n-butyl alcohol of 25ml that adds claims to decide weight, and supersound process 30 minutes is put cold, claim again to decide weight, supply the weight that subtracts mistake, filter, promptly with water saturated n-butyl alcohol.
Accurate respectively reference substance solution and each 10ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly.
Every of this product contains Fructus Psoraleae with psoralen (C
11H
6O
3) meter, must not be less than 0.12mg.
The above embodiment only is that preferred implementation of the present invention is described; be not that scope of the present invention is limited; design under the prerequisite of spirit not breaking away from the present invention; various distortion and improvement that the ability those of ordinary skill is made technical scheme of the present invention all should fall in the definite protection domain of claims of the present invention.
Claims (10)
1. a medicine for the treatment of the difficulty in urination is characterized in that it mainly is to be formed by the following weight parts feedstock production.
Fructus Psoraleae 240-360 part Herba Leonuri 360-560 part
Spora Lygodii 240-360 part Pseudobulbus Cremastrae Seu Pleiones 180-300 part.
2. the medicine of the treatment difficulty in urination as claimed in claim 1, wherein the consumption of each raw material is:
480 parts of 300 parts of Herba Leonuris of Fructus Psoraleae
240 parts of 300 parts of Pseudobulbus Cremastrae Seu Pleioness of Spora Lygodii.
3. the preparation method of medicine as claimed in claim 1 or 2, it comprises the following steps:
Take by weighing described four Chinese medicine material, wherein Spora Lygodii is decocted a drug wrapped, and adds 8 times of water gaging steaming and decoctings twice at every turn, and 3 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrate decompression is concentrated into 60 ℃ of survey relative densities and is about 1.35 clear paste, at 60 ℃ of following vacuum dryings, gets dry extract.
4. medicine as claimed in claim 1, wherein crude drug also has: Herba Lysimachiae 240-360g, succinum 24-36g.
5. medicine as claimed in claim 4, wherein the consumption of each raw material is:
300 parts of 480 portions of Herba Lysimachiaes of 300 parts of Herba Leonuris of Fructus Psoraleae
240 parts of 30 parts of Pseudobulbus Cremastrae Seu Pleioness of 300 parts of succinums of Spora Lygodii.
6. as the preparation method of claim 4 or 5 described medicines, it is characterized in that:
Take by weighing described Six-element medical material, Succinum powder is broken into fine powder, crosses 80 mesh sieves, and is standby; The five tastes such as all the other Fructus Psoraleaes, wherein Spora Lygodii is decocted a drug wrapped, and adds 8 times of water gaging steaming and decoctings twice at every turn, and 3 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrate decompression is concentrated into 60 ℃ of survey relative densities and is about 1.35 clear paste, at 60 ℃ of following vacuum dryings, gets dry extract.
7. as the method for quality control of claim 1-2, the described arbitrary medicine of 4-5, it is characterized in that this method comprises assay:
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica, are mobile phase with methanol-0.02mol/L potassium dihydrogen phosphate aqueous solution 20-80: 20-80, and the detection wavelength is 246nm; Flow velocity: 1ml/min; Number of theoretical plate calculates by the psoralen peak should be not less than 3000;
The preparation of reference substance solution 24 hours the psoralen reference substance of phosphorus pentoxide vacuum drying of learning from else's experience is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.05mg, promptly;
Medicine of the present invention is got in the preparation of need testing solution, porphyrize, and precision takes by weighing about 2g in tool plug conical flask, the accurate water saturated n-butyl alcohol of 25ml that adds, claim decide weight, supersound process 30 minutes is put coldly, and weight decided in title again, supply the weight that subtracts mistake with water saturated n-butyl alcohol, filter, promptly;
Accurate respectively reference substance solution and each 10ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly;
The every preparation unit of this product contains Fructus Psoraleae with psoralen C
11H
6O
3Meter must not be less than 0.12mg.
8. as method of quality control as described in the claim 7, it is characterized in that also comprising following one or more that differentiate:
(1) get medicine of the present invention, porphyrize takes by weighing 3g, adds n-butyl alcohol 30ml supersound process 1 hour, puts coldly, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets psoralen, the isopsoralen reference substance, add mixed solution that methanol makes psoralen that every 1ml contains 0.5mg, 2mg isopsoralen product solution in contrast, according to the thin layer chromatography test of Chinese Pharmacopoeia, draw each 10 μ l of above-mentioned two kinds of solution, putting in the same carboxymethyl cellulose rope sodium that contains respectively is on the silica gel g thin-layer plate of adhesive, with normal hexane-ethyl acetate of 7: 3 was developing solvent, launch, take out, dry; Put under the 254nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show two identical fluorescence speckles;
(2) get medicine of the present invention, porphyrize takes by weighing 2g, adds ethanol 30ml, supersound extraction 20 minutes, filter, filtrate is concentrated into about 5ml, is added on active carbon-alumina column of having handled well active carbon 0.6g wherein, 60-80 order, neutral alumina 2g, 100-200 order, mixing, dress post, column internal diameter 10mm; With ethanol 30ml eluting, collect eluent, evaporate to dryness, residue adds 6 → 1000 hydrochloric acid solution 2ml dissolving, filters, and filtrate is put to steam in the water-bath near and done, residue adds ethanol 0.5ml makes dissolving as need testing solution, other gets the stachydrine hydrochloride reference substance, adds ethanol and makes the solution that every 1ml contains 5mg, in contrast product solution.According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with n-butyl alcohol-hydrochloric acid of 12: 4.5: 1.5-ethyl acetate, launch, take out, to dry, spray is with rare bismuth potassium iodide test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
9. as the described arbitrary medicine of claim 4-5, it is characterized in that described medicine is a coated tablet, the preparation method of this coated tablet is: take by weighing described Six-element medical material, Succinum powder is broken into fine powder, crosses 80 mesh sieves, and is standby; The five tastes such as all the other Fructus Psoraleaes, wherein Spora Lygodii is decocted a drug wrapped, and adds 8 times of water gaging steaming and decoctings twice at every turn, and 3 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrate decompression is concentrated into 60 ℃ of survey relative densities and is about 1.35 clear paste, at 60 ℃ of following vacuum dryings, get dry extract, the dried cream powder that makes is broken, cross 80 mesh sieves, add described succinum fine powder and appropriate amount of starch, mixing, alcohol granulation with 80% is crossed 18 mesh sieves, and is dry down at 60 ℃, cross 18 mesh sieve granulate, add an amount of microcrystalline Cellulose and 0.1% magnesium stearate, be pressed into 1000, sugar coating promptly gets coated tablet.
10. the method for quality control of coated tablet as claimed in claim 9 is characterized in that this method comprises:
Differentiate:
(1) it is an amount of to get this product, remove sugar-coat after, porphyrize takes by weighing 3g, adds n-butyl alcohol 30ml supersound process 1 hour, puts coldly, filters, filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets psoralen, the isopsoralen reference substance, add mixed solution that methanol makes psoralen that every 1ml contains 0.5mg, 2mg isopsoralen product solution in contrast, according to the test of the thin layer chromatography of Chinese Pharmacopoeia, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in-to contain carboxymethyl cellulose rope sodium be on the silica gel g thin-layer plate of adhesive, with normal hexane-ethyl acetate of 7: 3 was developing solvent, launch, take out, dry; Put under the 254nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show two identical fluorescence speckles;
(2) it is an amount of to get this product, remove coating after, porphyrize, take by weighing 2g, add ethanol 30ml, supersound extraction 20 minutes, filter, filtrate is concentrated into about 5ml, is added on active carbon-alumina column of having handled well, active carbon 0.6g wherein, 60-80 order, neutral alumina 2g, the 100-200 order, mixing, dress post, column internal diameter 10mm; With ethanol 30ml eluting, collect eluent, evaporate to dryness, residue adds 6 → 1000 hydrochloric acid solution 2ml dissolving, filters, and filtrate is put to steam in the water-bath near and done, residue adds ethanol 0.5ml makes dissolving as need testing solution, other gets the stachydrine hydrochloride reference substance, adds ethanol and makes the solution that every 1ml contains 5mg, in contrast product solution.According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with n-butyl alcohol-hydrochloric acid of 12: 4.5: 1.5-ethyl acetate, launch, take out, to dry, spray is with rare bismuth potassium iodide test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
Assay:
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica, are at 45: 55 mobile phase with methanol-0.02mol/L potassium dihydrogen phosphate aqueous solution, and the detection wavelength is 246nm; Flow velocity: 1ml/min; Number of theoretical plate calculates by the psoralen peak should be not less than 3000;
The preparation of reference substance solution 24 hours the psoralen reference substance of phosphorus pentoxide vacuum drying of learning from else's experience is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.05mg, promptly;
20 of this product are got in the preparation of need testing solution, remove sugar-coat, porphyrize, and precision takes by weighing about 2g in tool plug conical flask, the accurate water saturated n-butyl alcohol of 25ml that adds claims to decide weight, and supersound process 30 minutes is put cold, claim again to decide weight, supply the weight that subtracts mistake, filter, promptly with water saturated n-butyl alcohol;
Accurate respectively reference substance solution and each 10ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly;
Every of this product contains Fructus Psoraleae with psoralen C
11H
6O
3Meter must not be less than 0.12mg.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104027634A (en) * | 2014-05-26 | 2014-09-10 | 烟台瑞智生物医药科技有限公司 | Traditional Chinese medicine for treating bladder damp-heat type retention of urine |
| CN104825803A (en) * | 2014-02-11 | 2015-08-12 | 姜莉莉 | Traditional Chinese patent medicine preparation for treating prostate diseases and preparation method thereof |
| CN105911210A (en) * | 2016-04-11 | 2016-08-31 | 株洲千金药业股份有限公司 | Discriminating method of Herba Leonuri component in Fukeduanhongyin capsule |
| CN115754094A (en) * | 2022-07-19 | 2023-03-07 | 石家庄科迪药业有限公司 | Fingerprint of urine retention relieving preparation and establishing method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152450A (en) * | 2007-10-10 | 2008-04-02 | 天津药业集团新郑股份有限公司 | Dysuria releasing tablet and method for preparing the same |
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2010
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101152450A (en) * | 2007-10-10 | 2008-04-02 | 天津药业集团新郑股份有限公司 | Dysuria releasing tablet and method for preparing the same |
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| Title |
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| 国家药典委员会标准一室: "癃闭舒胶囊质量标准", 《中国药品标准》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104825803A (en) * | 2014-02-11 | 2015-08-12 | 姜莉莉 | Traditional Chinese patent medicine preparation for treating prostate diseases and preparation method thereof |
| CN104027634A (en) * | 2014-05-26 | 2014-09-10 | 烟台瑞智生物医药科技有限公司 | Traditional Chinese medicine for treating bladder damp-heat type retention of urine |
| CN105911210A (en) * | 2016-04-11 | 2016-08-31 | 株洲千金药业股份有限公司 | Discriminating method of Herba Leonuri component in Fukeduanhongyin capsule |
| CN115754094A (en) * | 2022-07-19 | 2023-03-07 | 石家庄科迪药业有限公司 | Fingerprint of urine retention relieving preparation and establishing method and application thereof |
| CN115754094B (en) * | 2022-07-19 | 2024-04-19 | 石家庄科迪药业有限公司 | Finger print of uroschesis relieving preparation and establishing method and application thereof |
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