CN101254260B - Pharmaceutical combination for curing prostate gland hyperplasy, anuresis and preparation thereof - Google Patents
Pharmaceutical combination for curing prostate gland hyperplasy, anuresis and preparation thereof Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition for the treatment of prostatic hyperplasia and anuria, a preparation method and a quality control method. The pharmaceutical composition is composed of danshen root, hiraute shiny bugleweed herb, peach seed, safflower, red paeony root, dahurian angelica root, citron fruit, oriental waterplantain rhizome, cowherb seed, dahurian patrinia herb, Szechwan Chinaberry fruit, combined spicebush root and amur corktree bark; the preparation method is that: the pharmaceutical raw materials of the composition are taken, the conventional auxiliary materials are added, and a clinically acceptable preparation is prepared according to the conventional process. The invention adopts the high performance liquid chromatography for carrying out the content determination of berberine hydrochloride. The pharmaceutical composition of the invention has great efficacy in the treatment of the prostatic hyperplasia and the anuria.
Description
Invention field
The present invention relates to a kind of pharmaceutical composition and preparation method and method of quality control, particularly a kind of pharmaceutical composition and preparation method and method of quality control for the treatment of prostatic hyperplasia, urine retention.
Background technology
Prostatic hyperplasia has another name called prostate hyperplasia, and pilosity is born in the old people more than 50 years old.According to states such as America and Europe statistics, its sickness rate is up to more than 80% in elderly men; Domestic report is lower, but also reaches more than 50%.Because prostate is positioned at the bladder outlet place just, round the specific position of urethra, in case hypertrophy takes place, just can oppress urethra from all quarter, intravesical urine is discharged be obstructed, cause a series of pathological changes of urinary system, mainly cause the mechanical obstruction of urethra.Pathological development to late period because the depletion of bladder compensation, the bladder residual urine is more and more, intravesical pressure is increased cause dilatation of ureter and hydronephrosis, makes impaired renal function, concurrent hydronephrosis or uremia, consequence is extremely serious.
The treatment of prostatic hyperplasia mainly relies on medicine and operation, though operation is a treatment means the most completely, for slight hypertrophy and older and can not tolerate surgery person, medicine is still ideal treatment means.The medicine of treatment hyperplasia of prostate is broadly divided into following a few class at present: alpha-blocking agent, as phenoxybenzamine, tamsulosin hydrochloride etc.; The 5-alpha reductase inhibitor is as proscar, epristeride etc.; Chinese herbal compound preparation.Alpha-blocking agent can be alleviated and blocks, and improve symptom, but side effect is more, uses patient about 30% side effect such as postural hypotension, tachycardia, nasal obstruction to occur, and phenomenon can appear tolerating in life-time service, and expense is also expensive; The effect of 5-alpha reductase inhibitor is comparatively lasting, but expense is higher, and long-term efficacy remains further to be observed.
Compound Chinese medicinal preparation is fundamentally treated prostatic hyperplasia then according to theory of Chinese medical science at its pathogenic mechanism, has advantages such as determined curative effect, easy to use, no obvious toxic-side effects, preferablyly applies clinically.
Summary of the invention
The object of the invention is to provide a kind of pharmaceutical composition; Another purpose of the present invention is to provide a kind of pharmaceutical composition for the treatment of prostatic hyperplasia; The 3rd purpose of the present invention is to provide this preparation of drug combination method; The 4th purpose of the present invention is to provide the method for quality control of this pharmaceutical composition.
The present invention seeks to be achieved through the following technical solutions:
The crude drug of pharmaceutical composition of the present invention consists of: Radix Salviae Miltiorrhizae 100-200 weight portion, Herba Lycopi 20-80 weight portion, Semen Persicae 20-80 weight portion, Flos Carthami 100-200 weight portion, Radix Paeoniae Rubra 20-80 weight portion, Radix Angelicae Dahuricae 50-150 weight portion, Fructus Citri 50-150 weight portion, Rhizoma Alismatis 100-200 weight portion, Semen Vaccariae 100-200 weight portion, Herba Patriniae 200-300 weight portion, Fructus Toosendan 50-150 weight portion, Radix Linderae 50-150 weight portion, Cortex Phellodendri (processed with salt) 100-200 weight portion.
The crude drug of pharmaceutical composition of the present invention is formed can also be Radix Salviae Miltiorrhizae 100-200 weight portion, Herba Lycopi 20-80 weight portion, Semen Persicae 20-80 weight portion, Flos Carthami 100-200 weight portion, Radix Paeoniae Rubra 20-80 weight portion, Radix Angelicae Dahuricae 50-150 weight portion, Pericarpium Citri Reticulatae 50-150 weight portion, Rhizoma Alismatis 100-200 weight portion, Semen Vaccariae 100-200 weight portion, Herba Patriniae 200-300 weight portion, Fructus Toosendan 50-150 weight portion, Fructus Foeniculi (processed with salt) 50-150 weight portion, Cortex Phellodendri (processed with salt) 100-200 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Salviae Miltiorrhizae 100-130 weight portion, Herba Lycopi 60-80 weight portion, Semen Persicae 20-40 weight portion, Flos Carthami 160-200 weight portion, Radix Paeoniae Rubra 20-40 weight portion, Radix Angelicae Dahuricae 120-150 weight portion, Pericarpium Citri Reticulatae 50-80 weight portion, Rhizoma Alismatis 160-200 weight portion, Semen Vaccariae 100-130 weight portion, Herba Patriniae 260-300 weight portion, Fructus Toosendan 50-80 weight portion, Fructus Foeniculi (processed with salt) 120-150 weight portion, Cortex Phellodendri (processed with salt) 100-130 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Salviae Miltiorrhizae 115 weight portions, Herba Lycopi's 70 weight portions, Semen Persicae 30 weight portions, Flos Carthami 180 weight portions, Radix Paeoniae Rubra 30 weight portions, the Radix Angelicae Dahuricae 135 weight portions, Pericarpium Citri Reticulatae 75 weight portions, Rhizoma Alismatis 180 weight portions, Semen Vaccariae 115 weight portions, Herba Patriniae 280 weight portions, Fructus Toosendan 75 weight portions, Fructus Foeniculi (processed with salt) 135 weight portions, Cortex Phellodendri (processed with salt) 115 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Salviae Miltiorrhizae 125 weight portions, Herba Lycopi's 65 weight portions, Semen Persicae 35 weight portions, Flos Carthami 165 weight portions, Radix Paeoniae Rubra 35 weight portions, the Radix Angelicae Dahuricae 125 weight portions, Pericarpium Citri Reticulatae 75 weight portions, Rhizoma Alismatis 165 weight portions, Semen Vaccariae 125 weight portions, Herba Patriniae 265 weight portions, Fructus Toosendan 75 weight portions, Fructus Foeniculi (processed with salt) 125 weight portions, Cortex Phellodendri (processed with salt) 125 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Salviae Miltiorrhizae 160-200 weight portion, Herba Lycopi 20-40 weight portion, Semen Persicae 60-80 weight portion, Flos Carthami 100-130 weight portion, Radix Paeoniae Rubra 60-80 weight portion, Radix Angelicae Dahuricae 50-80 weight portion, Pericarpium Citri Reticulatae 120-150 weight portion, Rhizoma Alismatis 100-130 weight portion, Semen Vaccariae 160-200 weight portion, Herba Patriniae 200-230 weight portion, Fructus Toosendan 120-150 weight portion, Fructus Foeniculi (processed with salt) 50-80 weight portion, Cortex Phellodendri (processed with salt) 160-200 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Salviae Miltiorrhizae 180 weight portions, Herba Lycopi's 30 weight portions, Semen Persicae 70 weight portions, Flos Carthami 115 weight portions, Radix Paeoniae Rubra 70 weight portions, the Radix Angelicae Dahuricae 75 weight portions, Pericarpium Citri Reticulatae 135 weight portions, Rhizoma Alismatis 115 weight portions, Semen Vaccariae 180 weight portions, Herba Patriniae 215 weight portions, Fructus Toosendan 135 weight portions, Fructus Foeniculi (processed with salt) 75 weight portions, Cortex Phellodendri (processed with salt) 180 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Salviae Miltiorrhizae 165 weight portions, Herba Lycopi's 35 weight portions, Semen Persicae 65 weight portions, Flos Carthami 125 weight portions, Radix Paeoniae Rubra 65 weight portions, the Radix Angelicae Dahuricae 75 weight portions, Pericarpium Citri Reticulatae 125 weight portions, Rhizoma Alismatis 125 weight portions, Semen Vaccariae 165 weight portions, Herba Patriniae 225 weight portions, Fructus Toosendan 125 weight portions, Fructus Foeniculi (processed with salt) 75 weight portions, Cortex Phellodendri (processed with salt) 165 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Salviae Miltiorrhizae 140150 weight portions, Herba Lycopi 45-55 weight portion, Semen Persicae 45-55 weight portion, Flos Carthami 140-150 weight portion, Radix Paeoniae Rubra 45-55 weight portion, Radix Angelicae Dahuricae 90-110 weight portion, Pericarpium Citri Reticulatae 90-110 weight portion, Rhizoma Alismatis 140-150 weight portion, Semen Vaccariae 140-150 weight portion, Herba Patriniae 235-255 weight portion, Fructus Toosendan 90-110 weight portion, Fructus Foeniculi (processed with salt) 90-110 weight portion, Cortex Phellodendri (processed with salt) 140-150 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Salviae Miltiorrhizae 144 weight portions, Herba Lycopi's 48 weight portions, Semen Persicae 48 weight portions, Flos Carthami 144 weight portions, Radix Paeoniae Rubra 48 weight portions, the Radix Angelicae Dahuricae 96 weight portions, Pericarpium Citri Reticulatae 96 weight portions, Rhizoma Alismatis 144 weight portions, Semen Vaccariae 144 weight portions, Herba Patriniae 240 weight portions, Fructus Toosendan 96 weight portions, Fructus Foeniculi (processed with salt) 96 weight portions, Cortex Phellodendri (processed with salt) 144 weight portions.
Preparation of pharmaceutical compositions method of the present invention is: above 13 flavors, and Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 4-8 and doubly measure the 50-70% alcohol reflux 1-3 time, and each 1-3 hour, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 8-12 times of water gaging and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 1-3 time, add 4-10 times of water gaging at every turn and decoct collecting decoction 1-4 hour, filter, filtrate and medicinal liquid merging are condensed into 50 ℃ of relative densities and are 1.20～1.40 extractum, drying is ground into fine powder II, and fine powder II adds fine powder I mixing, make granule, drying adds volatile oil such as above-mentioned Fructus Foeniculi, adds conventional adjuvant, through conventional method, make the preparation of clinical acceptance.
Preparation of pharmaceutical compositions method of the present invention is preferably: above 13 flavors, and Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 6 times of amount 60% alcohol reflux 2 times, and each 2 hours, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 10 times of water gagings and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 2 times, add 8 times of water gagings for the first time and decoct 3 hours, add 6 times of water gagings for the second time and decoct 2 hours, collecting decoction filters, and filtrate and medicinal liquid merge, be condensed into 50 ℃ of relative densities and be 1.28～1.30 extractum, drying is ground into fine powder II, fine powder II adds fine powder I mixing, makes granule, drying, add volatile oil such as above-mentioned Fructus Foeniculi, add conventional adjuvant,, make the oral solid formulation of clinical acceptance through conventional method.
Pharmaceutical composition method of quality control of the present invention comprises one or more in following discrimination method and/or the assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, the 0.05mol/L NaH2PO4 buffer solution (H of 50-90:10-50 ratio
3PO
4Transferring pH is 3.0 ± 0.5)-acetonitrile is a mobile phase; The detection wavelength is 270nm; Number of theoretical plate is pressed the berberine hydrochloride peak and is calculated, and should be not less than 1500;
The preparation of reference substance solution: it is an amount of that the berberine hydrochloride reference substance decided in accurate title, adds methanol and make the solution that every 1ml contains 10 μ g;
The preparation of need testing solution: precision takes by weighing the accurate methanol 50ml that adds of the preparation content that is equivalent to crude drug content 1/600-1/800, claim to decide weight, supersound process 30 minutes is put cold title again and is decided weight, supplies the weight that subtracts mistake with methanol, shake up, leave standstill, get supernatant, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly;
Pharmaceutical composition per unit preparation of the present invention contains Cortex Phellodendri with berberine hydrochloride C
20H
18ClNO
4Meter must not be less than 0.10mg;
Discrimination method: A, get the preparation content that is equivalent to crude drug content 1/100-1/300, remove sugar-coat, porphyrize, the 15ml that adds diethyl ether, jolting was extracted 5 minutes, filtered; Get filtrate 5ml, volatilize, residue adds 1 of 1% vanillin sulfuric acid solution, and drop edge is purple; Other gets filtrate 5ml, volatilize, residue add glacial acetic acid a little, make dissolving, add 1 in sulphuric acid again, slight fever, solution shows purple brown;
B, get the preparation content that is equivalent to crude drug content 1/100-1/300, remove sugar-coat, porphyrize adds ethanol 10ml, and jolting was extracted 10 minutes, filters, and filtrate adds magnesium powder a little and salt acid number to be dripped, and puts in the water-bath and heats, and it is red that solution shows;
C, to get drug combination preparation of the present invention an amount of, removes sugar-coat, is ground into powder, take by weighing the powder that is equivalent to crude drug content 1/70, add methanol 50ml supersound extraction half an hour, filter, filtrate is added on the 100-120 order, and 5g is on the neutral alumina post of internal diameter 10-15mm, with 40% methanol 50ml eluting, eluent evaporate to dryness, add water 15ml dissolving, aqueous solution water saturation n-butanol extraction twice, each 15ml merges n-butyl alcohol liquid, with the saturated washing twice of n-butyl alcohol, each 10ml; Discard water layer, n-butanol extracting liquid evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the Hesperidin reference substance, adds methanol and makes saturated solution, in contrast product; Test according to thin layer chromatography, draw above-mentioned reference substance 4 μ l, test sample 8 μ l, point sample is on same silica gel G plate respectively, lower floor's solution with the chloroform-methanol-water of 5-25:5-15:1-3 ratio is developing solvent, launch, take out, dry, spray places under the 365nm ultra-violet lamp and inspects with the aluminum chloride test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
D, get the peoniflorin reference substance in addition, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw reference substance, each 5 μ l of test sample among the discrimination method C, respectively point sample is on same silica gel G plate, is developing solvent with the chloroform-ethyl acetate-methanol-formic acid of 20-60:1-10:5-15:0.1-0.3 ratio, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, to get drug combination preparation of the present invention an amount of, removes sugar-coat, is ground into powder, takes by weighing the powder that is equivalent to crude drug content 1/3500-1/700, added methanol 10ml ultrasonic 5 minutes, filters, and evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 1 μ l of above-mentioned two kinds of solution, point sample is on same silica gel G plate respectively, benzene-ethyl acetate-isopropyl alcohol-methanol-strong ammonia solution with the 4-8:1-5:0.5-2.5:0.5-2.5:0.1-1.0 ratio is developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Pharmaceutical composition method of quality control of the present invention is preferably as follows one or more in discrimination method and/or the assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, the 0.05mol/L NaH of 73:27 ratio
2PO
4Buffer solution (H
3PO
4Transferring pH is 3.0 ± 0.5)-acetonitrile is a mobile phase; The detection wavelength is 270nm; Number of theoretical plate is pressed the berberine hydrochloride peak and is calculated, and should be not less than 1500;
The preparation of reference substance solution: it is an amount of that the berberine hydrochloride reference substance decided in accurate title, adds methanol and make the solution that every 1ml contains 10 μ g;
The preparation of need testing solution: precision takes by weighing the preparation content that is equivalent to crude drug content 1/700, the accurate methanol 50ml that adds claims to decide weight, supersound process 30 minutes, put the cold weight that claims to decide again, supply the weight that subtracts mistake with methanol, shake up, leave standstill, get supernatant, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly;
Pharmaceutical composition per unit preparation of the present invention contains Cortex Phellodendri in berberine hydrochloride C20H18ClNO4, must not be less than 0.10mg;
Discrimination method: A, get the preparation content that is equivalent to crude drug content 1/200, remove sugar-coat, porphyrize, the 15ml that adds diethyl ether, jolting was extracted 5 minutes, filtered; Get filtrate 5ml, volatilize, residue adds 1 of 1% vanillin sulfuric acid solution, and drop edge is purple; Other gets filtrate 5ml, volatilize, residue add glacial acetic acid a little, make dissolving, add 1 in sulphuric acid again, slight fever, solution shows purple brown;
B, get the preparation content that is equivalent to crude drug content 1/200, remove sugar-coat, porphyrize adds ethanol 10ml, and jolting was extracted 10 minutes, filters, and filtrate adds magnesium powder a little and salt acid number to be dripped, and puts in the water-bath and heats, and it is red that solution shows;
C, to get drug combination preparation of the present invention an amount of, removes sugar-coat, is ground into powder, take by weighing the powder that is equivalent to crude drug content 1/70, add methanol 50ml supersound extraction half an hour, filter, filtrate is added on the 100-120 order, and 5g is on the neutral alumina post of internal diameter 10-15mm, with 40% methanol 50ml eluting, eluent evaporate to dryness, add water 15ml dissolving, aqueous solution water saturation n-butanol extraction twice, each 15ml merges n-butyl alcohol liquid, with the saturated washing twice of n-butyl alcohol, each 10ml; Discard water layer, n-butanol extracting liquid evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the Hesperidin reference substance, adds methanol and makes saturated solution, in contrast product; According to thin layer chromatography test, draw above-mentioned reference substance 4 μ l, test sample 8 μ l, point sample is on the silica gel G plate respectively, lower floor's solution with the chloroform-methanol-water of 13:7:2 ratio is developing solvent, launches, and takes out, dry, spray places under the 365nm ultra-violet lamp and inspects with the aluminum chloride test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
D, get the peoniflorin reference substance in addition, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw reference substance, each 5 μ l of test sample among the discrimination method C, respectively point sample is on same silica gel G plate, is developing solvent with the chloroform-ethyl acetate-methanol-formic acid of 40:5:10:0.2 ratio, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, to get drug combination preparation of the present invention an amount of, removes sugar-coat, is ground into powder, takes by weighing the powder that is equivalent to crude drug content 3/3500, added methanol 10ml ultrasonic 5 minutes, filters, and evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 1 μ l of above-mentioned two kinds of solution, point sample is on same silica gel G plate respectively, benzene ethyl acetate isopropyl alcohol-methanol-strong ammonia solution with the 6:3:1.5:1.5:0.5 ratio is developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Pharmaceutical composition prescription of the present invention is with ancient prescription and the theoretical combination of modern Chinese medicine, Radix Salviae Miltiorrhizae, Flos Carthami, Semen Persicae, Radix Paeoniae Rubra in the side, clearing away heat and cooling blood, promoting blood circulation to restore menstrual flow, stasis-dispelling and pain-killing; The Radix Angelicae Dahuricae, Cortex Phellodendri, Rhizoma Alismatis, heat clearing and damp drying, relieving stranguria by diuresis; Fructus Citri, the Radix Linderae, promoting the circulation of QI to relieve pain; Three groups of medicines match, vital energy regualting and blood circulation-promoting, and the eliminating stagnation of stimulating the menstrual flow is used for the treatment of hyperplasia of prostate, and symptom such as the nocturia number of times that causes increases suddenly, urgent micturition, dysurea, hematuria and heating has good effect.Pharmaceutical composition of the present invention confirms through experimentation: can have contraction to urethral smooth muscle, prostate smooth muscle, impel the pathological model of prostate hyperplasia to recover to end normal; The effect of dihydrotestosterone receptor capable of blocking, and the activity that suppresses 5a-reductase and 3-hydroxyl dehydrogenase, testosterone is converted into dihydrotestosterone in the body thereby stop, and suppresses body of prostate and increases; But clearing away heat and cooling blood, promoting blood circulation to restore menstrual flow, stasis-dispelling and pain-killing improve the partial blood circulation of prostate, help the drain of pathological tissues rheuminess thing, eliminate symptomatic reaction; Anhydroalkannin, infection promotes organism metabolism and hemopoietic, the enhancing human body immunity function.
The present composition is compared the easypro ball in existing preparation prostatitis and is possessed good drug effect, and scope of the present invention through screening, finds in some scope of compositions, to possess more outstanding drug effect unexpectedly when can realizing drug effect of the present invention.
The method of quality control of Chinese medicine composition provided by the present invention, be by obtaining behind the creative experiment sieving of big measuring, pass through screening in the discrimination method to sample treatment, the selection of developing solvent, make and differentiate that specificity is fine, and method is economic and practical, the result is quick, and can both use different lamellaes.Pass through screening in the content assaying method to sample, test sample processing method, the selection of developing solvent, make content assaying method effectivelyly to carry out quality control, and compare more stable that product that additive method measures shows on drug effect with the product that this method is measured to product.
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
Experimental example 1 medicine is to the clinical efficacy of prostatic hyperplasia
Medicine group I (Radix Salviae Miltiorrhizae 115g, Herba Lycopi 70g, Semen Persicae 30g, Flos Carthami 180g, Radix Paeoniae Rubra 30g, Radix Angelicae Dahuricae 135g, Pericarpium Citri Reticulatae 75g, Rhizoma Alismatis 180g, Semen Vaccariae 115g, Herba Patriniae 280g, Fructus Toosendan 75g, Fructus Foeniculi (processed with salt) 135g, Cortex Phellodendri (processed with salt) 115g)
Medicine group II (Radix Salviae Miltiorrhizae 125g, Herba Lycopi 65g, Semen Persicae 35g, Flos Carthami 165g, Radix Paeoniae Rubra 35g, Radix Angelicae Dahuricae 125g, Pericarpium Citri Reticulatae 75g, Rhizoma Alismatis 165g, Semen Vaccariae 125g, Herba Patriniae 265g, Fructus Toosendan 75g, Fructus Foeniculi (processed with salt) 125g, Cortex Phellodendri (processed with salt) 125g)
Medicine group III (Radix Salviae Miltiorrhizae 144g, Herba Lycopi 48g, Semen Persicae 48g, Flos Carthami 144g, Radix Paeoniae Rubra 48g, Radix Angelicae Dahuricae 96g, Pericarpium Citri Reticulatae 96g, Rhizoma Alismatis 144g, Semen Vaccariae 144g, Herba Patriniae 240g, Fructus Toosendan 96g, Fructus Foeniculi (processed with salt) 96g, Cortex Phellodendri (processed with salt) 144g).
According to medicine group I, medicine group II and medicine group III prescription ratio, prepare pharmaceutical preparation of the present invention according to selection process, respectively organize the clinical efficacy of Drug therapy prostatitis prostatic hyperplasia, choose through suffering from patient's 120 examples of prostatic hyperplasia, be divided into 3 groups at random,, take the above course of treatment of medicine of the present invention of respectively organizing respectively through state of an illness distribution there was no significant difference between each group relatively, relatively the state of an illness is improved situation, the results are shown in Table 1.
Table 1 medicine of the present invention is to the clinical efficacy of prostatic hyperplasia symptom
Annotate: * compares P＜0.05 with medicine group III
The result shows: the medicine group III of the present invention significant difference (P＜0.05) of having compared with other group, medicine group I of the present invention, II treatment prostatic hyperplasia effect is better than the III group.
The clinical comparative test of ball of relaxing of 2 of the present invention groups of IV pharmaceutical preparatioies of experimental example and prostatitis
Medicine group IV (Radix Salviae Miltiorrhizae 144g, Herba Lycopi 48g, Semen Persicae 48g, Flos Carthami 144g, Radix Paeoniae Rubra 48g, Radix Angelicae Dahuricae 96g, Fructus Citri 96g, Rhizoma Alismatis 144g, Semen Vaccariae 144g, Herba Patriniae 240g, Fructus Toosendan 96g, Radix Linderae 96g, Cortex Phellodendri (processed with salt) 144g) makes according to the method for embodiment
Matched group: the prostatitis ball that relaxes,
This group patient amounts to 204 examples, chronic prostatitis test group 61 people wherein, and matched group 60 examples, preceding gland hypertrophy test group 43 examples of splitting, matched group 40 examples, all cases are the outpatient, once making a definite diagnosis the observation of promptly taking medicine at random.
(1) age distribution
1, two groups of age distribution of chronic prostatitis (seeing Table 2)
Two groups of patient ages of table 2 chronic prostatitis distribute
| n | 18～30 years old | 31～40 years old | More than 41 years old | Minimal ages | The maximum age | |
| Test group | 61 | 16 | 18 | 27 | 18 | 65 |
| Matched group | 60 | 13 | 19 | 28 | 20 | 64 |
Learn by statistics and handle p＜0.05, two group age differences nonsignificance.
2, prostatic hyperplasia patient, age distribution (seeing Table 3)
Seeing Table two groups of patient ages of 3 hyperplasia of prostates distributes
| n | " 50 years old | 51～60 years old | 61～70 years old | |
| Test group | 43 | 16 | 18 | 2728 |
| Matched group | 40 | 13 | 19 |
Learn by statistics and handle p＜0.05, two group age differences nonsignificance.
(2) course of disease distribution (seeing Table 2)
Table 4 a liang group patient course of disease distributes
| " 6 months | ～1 year | ～2 years | 2～4 years | " 4 years | ||
| Prostatitis | Test group | 30 | 16 | 8 | 4 | 3 |
| Matched group | 25 | 19 | 6 | 4 | 6 | |
| Prostatic hyperplasia | Test group | 2 | 6 | 7 | 11 | 17 |
| Matched group | 1 | 6 | 9 | 8 | 16 |
Learn by statistics and handle p＜0.05, two group age differences nonsignificance.
(3) two groups of main analysis of clinical
Two groups of main analysis of clinical of patient of table 5 prostatitis
| Project | Gently (9) | In (6) | Heavy (5) | Add up to | Gently (6) | In (8) | Heavy (6) | Add up to | U | P |
| The perineum distending pain | 13 | 24 | 17 | 54 | 15 | 28 | 14 | 57 | 0.62 | >0.05 |
| Frequent micturition | 11 | 25 | 17 | 53 | 6 | 26 | 17 | 49 | 0.69 | >0.05 |
| Urgent micturition | 17 | 18 | 14 | 49 | 11 | 16 | 10 | 37 | 0.2 | >0.05 |
| Dysurea | 13 | 22 | 13 | 48 | 16 | 24 | 11 | 11 | 0.62 | >0.05 |
| The situation of urinating | 31 | 10 | 6 | 47 | 22 | 8 | 5 | 5 | 0.25 | >0.05 |
| Touch | 18 | 31 | 12 | 61 | 14 | 37 | 9 | 9 | 0.16 | >0.05 |
| EPS | 16 | 29 | 16 | 61 | 17 | 32 | 11 | 11 | 0.70 | >0.05 |
Learn to handle P by statistics〉0.05, two group of data distributional difference nonsignificance.
Two groups of main analysis of clinical of patient of table 6 prostatic hyperplasia
| Gently (9) | In (6) | Heavy (5) | Add up to | Gently (6) | In (8) | Heavy (6) | Add up to | U | P | |
| The perineum distending pain | 6 | 17 | 11 | 34 | 7 | 19 | 5 | 31 | 1.16 | >0.05 |
| Frequent micturition | 4 | 19 | 16 | 39 | 4 | 20 | 11 | 35 | 0.69 | >0.05 |
| Urgent micturition | 9 | 9 | 15 | 33 | 10 | 19 | 5 | 34 | 1.67 | >0.05 |
| Dysurea | 11 | 5 | 9 | 25 | 20 | 2 | 1 | 23 | 2.71 | 《0.01 |
| The situation of urinating | 15 | 12 | 13 | 40 | 15 | 15 | 7 | 37 | 0.80 | >0.05 |
| Touch | 12 | 16 | 15 | 43 | 13 | 19 | 8 | 40 | 1.08 | >0.05 |
| B ultrasonic | 12 | 16 | 5 | 43 | 11 | 20 | 9 | 40 | 0.68 | >0.05 |
Learn to handle by statistics, (P " 0.01 ", all the other symptom weight distributional differences do not have significance meaning (P〉0.05) except that test group hyperplasia of prostate dysurea symptom severity extent overweights the matched group.
(4) two groups of state of an illness weights compare (seeing Table 4)
Table 7 liang group state of an illness weight relatively
Statistical procedures P〉0.05, two group of state of an illness weight distributional difference nonsignificance.
Comprehensive above-mentioned clinical data, two groups of ordinary circumstances of chronic prostatitis and hyperplasia of prostate are compared, and all distribute balanced [except that experimental group hyperplasia of prostate dysurea symptom severity extent overweights (P＜0.01) the matched group] learned by statistics and handled P〉0.05, the difference nonsignificance has comparability.
Three, test method adopts the random table grouping
(1) administrated method
(1) test group: oral medicine of the present invention;
(2) matched group: ball relaxes in oral prostatitis.
The medicine and the therapy of inactive other treatment prostatitis of duration of test or hyperplasia of prostate
(2) course of treatment: chronic prostatitis 3 weeks of taking medicine are a course of treatment, promptly finish to observe, and the hyperplasia of prostate patient judges curative effect after taking two courses of treatment.
(3) observation index
1, safety observation
(1) general physical examination project;
(2) hematuria routine test;
(3) liver, kidney function test.
2, health giving quality observation
(1) tcm symptom, tongue, arteries and veins change observation;
(2) prostate rectal touch;
(3) prostatic fluid conventional sense or B ultrasonic observation prostate size and residual urine volume situation.
Four, result of the test
(1) clinical efficacy evaluation criteria
1, chronic prostatitis clinical effectiveness evaluation criteria
(1) clinical recovery: subjective symptoms disappearance, prostate touch quality recover normal or improve, and tenderness disappears, the prostatic fluid microscopy, and continuous 2 recoveries are normal.
(2) produce effects: transference cure, prostate touch improved texture, tenderness obviously alleviates, and prostatic fluid microscopy leukocyte is normal.
(3) effective: symptom and prostate improved texture, tenderness alleviates, but prostatic fluid microscopy leukocyte does not recover normal.
(4) invalid: symptom, sign, prostate touch do not have improvement, and the prostate microscopy does not have improvement.
2, hyperplasia of prostate clinical effectiveness evaluation criteria
(1) clinical recovery: primary symptom disappears, symptom total mark≤2 minute; The bladder residual urine volume does not have recurrence less than 20ml after the drug withdrawal, it is normal that body of prostate size, quality, form are all recovered.
(2) produce effects: main symptom obviously alleviates, and the symptom total mark descends 〉=2/3; Residual urine volume is still at 20～30ml; Prostate size, quality, form are near normal.
(3) effective: primary symptom is improved, and the symptom total mark descends 〉=1/3; But residual urine volume is at 40～60ml; It is normal that body of prostate size, quality, form are not recovered.
(4) invalid: symptom and sign do not have improvement or the anti-person of increasing the weight of.
(2) result
1, total effects sees Table 5
Table 5 liang group curative effect
Learn by statistics and handle chronic prostatitis group P＜0.001, difference has extremely significantly meaning.Hyperplasia of prostate group P＜0.01, the difference significance.Medicine of the present invention and control drug are described relatively, its clinical effectiveness has utmost point significant difference.
2, two of test group groups of different state of an illness curative effects relatively see Table 6
Two groups of different state of an illness curative effects of table 6 test group relatively
Two groups of different state of an illness curative effects of test group are compared, and learn by statistics and handle P〉0.05 difference nonsignificance.
3, two groups of main clinical datas improve analysis (table 7)
The main clinical data of table 7-1 prostatitis improves to be analyzed
| The example number | Disappear | Improve | No change | Increase the weight of | The example number | Disappear | Improve | No change | Increase the weight of | U | P | |
| The perineum distending pain | 54 | 23 | 25 | 6 | 0 | 57 | 16 | 25 | 16 | 0 | 2.07 | 《0.05 |
| Frequent micturition | 53 | 34 | 13 | 6 | 0 | 49 | 13 | 24 | 12 | 0 | 3.33 | 《0.01 |
| Urgent micturition | 49 | 41 | 5 | 3 | 0 | 37 | 13 | 10 | 14 | 0 | 4.04 | 《0.001 |
| Dysurea | 48 | 37 | 8 | 3 | 0 | 51 | 25 | 10 | 14 | 2 | 2.52 | 《0.05 |
| The situation of urinating | 47 | 33 | 6 | 8 | 0 | 35 | 14 | 8 | 13 | 0 | 2.41 | 《0.05 |
| Touch | 61 | 27 | 24 | 10 | 0 | 60 | 12 | 21 | 27 | 0 | 3.45 | 《0.01 |
| B ultrasonic | 61 | 34 | 18 | 9 | 0 | 60 | 16 | 23 | 21 | 0 | 3.21 | 《0.01 |
Two groups of cardinal symptoms are improved situation analysis, learn by statistics and handle, and test group is improved situation and obviously is better than matched group, P＜0.05, and difference has the significance meaning.
Two groups of main clinical datas of table 7-2 hyperplasia of prostate improve to be analyzed
| The example number | Disappear | Improve | No change | Increase the weight of | The example number | Disappear | Improve | No change | Increase the weight of | U | P | |
| The perineum distending pain | 34 | 18 | 11 | 5 | 0 | 31 | 10 | 8 | 13 | 0 | 2.12 | 《0.05 |
| Frequent micturition | 39 | 5 | 25 | 9 | 0 | 35 | 4 | 12 | 19 | 0 | 2.10 | 《0.05 |
| Urgent micturition | 33 | 13 | 15 | 5 | 0 | 34 | 6 | 9 | 19 | 0 | 3.06 | 《0.05 |
| Dysurea | 25 | 16 | 3 | 6 | 0 | 23 | 9 | 3 | 11 | 0 | 1.65 | 》0.05 |
| The situation of urinating | 40 | 14 | 20 | 6 | 0 | 37 | 8 | 8 | 21 | 0 | 2.92 | 《0.01 |
| Touch | 43 | 7 | 23 | 13 | 0 | 40 | 5 | 10 | 25 | 0 | 2.34 | 《0.05 |
| B ultrasonic | 43 | 5 | 16 | 22 | 0 | 40 | 6 | 11 | 23 | 0 | 0.13 | 》0.05 |
Two groups of cardinal symptoms are improved analysis, learn by statistics and handle, except that dysurea, B ultrasonic improve two groups of difference nonsignificances of situation P〉0.05, the equal significance of all the other symptom differences (P＜0.05, P＜0.01).Illustrate that medicine of the present invention is better than the control drug group in clinical symptoms aspect improving.
Experimental example 3 quality standards
The method of quality control of Chinese medicine composition provided by the present invention is by obtaining behind the creative experiment sieving of big measuring, existing part test is disclosed as follows:
1, the thin layer discrimination method of Pericarpium Citri Reticulatae
1. the sample solution extracting method is preferred among the discrimination method C of the present invention:
Get 6 parts of pharmaceutical preparatioies of the present invention that are equivalent to crude drug 7.5g, add 50ml methanol respectively, be divided into 2 groups, adopt supersound extraction and reflux, extract, method to extract 30min, measure two groups of content of hesperidin that extract, the results are shown in following table:
| Extracting method | Supersound extraction | Reflux, extract, |
| Content of hesperidin (mg/g) | 0.856 | 0.513 |
As can be seen from the above table, after the supersound extraction in the sample solution content of hesperidin be significantly higher than reflux, extract.
2. the sample solution supersound extraction time is preferred among the discrimination method C of the present invention:
Get 5 parts of pharmaceutical preparatioies of the present invention that are equivalent to crude drug 7.5g,, measure content of hesperidin in the extracting solution, the results are shown in following table with methanol supersound extraction different time:
| Extraction time (min) | 10 | 20 | 30 | 40 | 60 |
| Content of hesperidin (mg/g) | 0.462 | 0.702 | 0.859 | 0.861 | 0.860 |
As can be seen from the above table, supersound extraction 30min just can extract Hesperidin wherein fully, is 30min so this tests preferred extraction time.
The compound method of preferred need testing solution is: take by weighing pharmaceutical preparation 5g of the present invention, add methanol 50ml supersound extraction half an hour, filter, filtrate is added on the neutral alumina post (100-120 order, 5g, internal diameter 10-15mm), with 40% methanol 50ml eluting, the eluent evaporate to dryness adds water 15ml dissolving, twice of water saturation n-butanol extraction of aqueous solution, each 15ml, merge n-butyl alcohol liquid, with the saturated washing twice of n-butyl alcohol, each 10ml.Discard water layer, n-butanol extracting liquid evaporate to dryness, residue add methanol 2ml dissolving, preferred as developing solvent proportioning among the need testing solution discrimination method C 3. of the present invention:
Get totally 5 parts of test sample 8 μ l, with chloroform-methanol-water proportioning is that lower floor's solution of (7:5:2), (13:7:2), (15:8:2), (20:10:3), (25:12:2) is developing solvent, point sample is on the silica gel G plate respectively, launch, take out, dry, spray places under the ultra-violet lamp (365nm) and inspects with the aluminum chloride test solution.Observe the unfolded effect of need testing solution on each thin layer version, the results are shown in following table:
| The developing solvent proportioning | 7：5：2 | 13：7：2 | 15：8：2 | 20：10：3 | 25：12：2 |
| Launch effect | Difference | Good | Relatively poor | Difference | Very poor |
When developing solvent proportioning as can be seen from the above table was 13:7:2, it is best that need testing solution launches effect, phenomenons such as hangover, the principal spot separation is bad, colour developing is unintelligible occur.
4. sample solution point sample amount is preferred among the discrimination method C of the present invention:
Get need testing solution 2 μ l, 4 μ l, 6 μ l, 8 μ l, reference substance solution 4 μ l, respectively point sample is on same silica gel G plate, is developing solvent with lower floor's solution of chloroform-methanol-water (13:7:2), launches, take out, dry, spray places under the ultra-violet lamp (365nm) and inspects with the aluminum chloride test solution, observe the effect of test sample principal spot colour developing on the lamellae, the results are shown in following table:
| The point sample amount | 2μl | 4μl | 6μl | 8μl |
| Effect | Test sample is at corresponding reference substance position immaculate | Test sample is very shallow in corresponding reference substance position spot colors | Test sample is shallow in corresponding reference substance position spot colors | Test sample is good at corresponding reference substance position speckle color developing effect |
Test sample point sample amount is when 8 μ l as can be seen from the above table, and color developing effect is good on lamellae, is fit to test requirements document.
5. negative control test
Get the negative sample that lacks Pericarpium Citri Reticulatae, prepare negative control solution, launch the back and corresponding speckle on the reference substance solution correspondence position, do not occur, illustrate that selected identification experiment specificity is strong according to need testing solution preparation method among the above-mentioned discrimination method C.
2, the thin layer discrimination method of Radix Paeoniae Rubra
The preparation method of need testing solution was identical with discriminating C during the Radix Paeoniae Rubra thin layer was differentiated. following research has been done in the discriminating of Radix Paeoniae Rubra in the medicine of the present invention:
1. the developing solvent proportioning is preferred among the discrimination method D of the present invention:
Get and differentiate among the C totally 4 parts of each 5 μ l of test sample, point sample is on the silica gel G plate respectively, with chloroform-ethyl acetate-methanol-formic acid proportioning is that (20:1:5:0.1), (30:5:10:0.1), (40:5:10:0.2), (60:10:15:0.3) are developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing.Observe the unfolded effect of need testing solution on each thin layer version, the results are shown in following table:
| The developing solvent proportioning | 20:1:5:0.1 | 30:5:10:0.1 | 40:5:10:0.2 | 60:10:15:0.3 |
| Launch effect | Difference | Relatively poor | Good | Difference |
When developing solvent proportioning as can be seen from the above table was 40:5:10:0.2, it is best that need testing solution launches effect, phenomenons such as hangover, the principal spot separation is bad, colour developing is unintelligible occur.
2. sample solution point sample amount is preferred among the discrimination method D of the present invention:
Get need testing solution 1 μ l, 2 μ l, 3 μ l, 5 μ l, point sample is on the silica gel G plate respectively, with chloroform-ethyl acetate-methanol-formic acid proportioning is that (40:5:10:0.2) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, it is clear to be heated to the speckle colour developing, and the effect of observing test sample principal spot colour developing on the lamellae the results are shown in following table:
| The point sample amount | 1μl | 2μl | 3μl | 5μl |
| Effect | Test sample is at corresponding reference substance position immaculate | Test sample is very shallow in corresponding reference substance position spot colors | Test sample is shallow in corresponding reference substance position spot colors | Test sample is good at corresponding reference substance position speckle color developing effect |
Test sample point sample amount is when 5 μ l as can be seen from the above table, and color developing effect is good on lamellae, is fit to test requirements document.
3. negative control test
Get the negative sample that lacks Radix Paeoniae Rubra, prepare negative control solution, launch the back and corresponding speckle on the reference substance solution correspondence position, do not occur, illustrate that selected identification experiment specificity is strong according to need testing solution preparation method among the above-mentioned discrimination method D.
3, the thin layer discrimination method of Cortex Phellodendri
1. the sample solution supersound extraction time is preferred among the discrimination method E of the present invention:
Get 5 parts of pharmaceutical preparatioies of the present invention that are equivalent to crude drug 7.5g,, measure content of hesperidin in the extracting solution, the results are shown in following table with methanol supersound extraction different time:
| Extraction time (min) | 1 | 3 | 5 | 7 | 10 |
| Content of berberine hydrochloride (mg/g) | 0.03 | 0.12 | 0.43 | 0.48 | 0.47 |
As can be seen from the above table, supersound extraction 5min just can extract berberine hydrochloride wherein fully substantially, is 5min so this tests preferred extraction time.
The compound method of preferred need testing solution is: take by weighing this law invention pharmaceutical preparation content 0.3g, added methanol 10ml ultrasonic 5 minutes, filter, evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution.
2. the developing solvent proportioning is preferred among the discrimination method E of the present invention:
Get totally 4 parts of need testing solution 1 μ l, point sample is on the silica gel G plate respectively, with benzene-ethyl acetate-isopropyl alcohol-methanol-strong ammonia solution proportioning is that (4:1:0.5:0.5:0.1), (6:3:1.0:1.0:0.5), (6:5:1.0:1.5:0.5), (6:3:2.0:2.0:1.0) are developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the ultra-violet lamp (365nm) and inspect.Observe the unfolded effect of need testing solution on each thin layer version, the results are shown in following table:
| The developing solvent proportioning | 4:1:0.5:0.5:0.1 | 6:3:1.0:1.0:0.5 | 6:5:1.0:1.5:0.5 | 6：3：2.0：2.0：1.0 |
| Launch effect | Difference | Good | Difference | Difference |
When developing solvent proportioning as can be seen from the above table was 13:7:2, it is best that need testing solution launches effect, phenomenons such as hangover, the principal spot separation is bad, colour developing is unintelligible occur.
3. sample solution point sample amount is preferred among the discrimination method E of the present invention:
Get totally 4 parts of need testing solution 0.2 μ l, 0.5 μ l, 0.7 μ l, 1 μ l, point sample is on the silica gel G plate respectively, with benzene-ethyl acetate-isopropyl alcohol-methanol-strong ammonia solution (6:3:1.0:1.0:0.5) is developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the ultra-violet lamp (365nm) and inspect, observe the effect of test sample principal spot colour developing on the lamellae, the results are shown in following table:
| The point sample amount | 0.2μl | 0.5μl | 0.7μl | 1 μ l test sample is good at corresponding reference substance position speckle color developing effect |
| Effect | Test sample is at corresponding reference substance position immaculate | Test sample is very shallow in corresponding reference substance position spot colors | Test sample is shallow in corresponding reference substance position spot colors |
Test sample point sample amount is when 1 μ l as can be seen from the above table, and color developing effect is good on lamellae, is fit to test requirements document.
4. negative control test
Get the negative sample that lacks Cortex Phellodendri, prepare negative control solution, launch the back and corresponding speckle on the reference substance solution correspondence position, do not occur, illustrate that selected identification experiment specificity is strong according to need testing solution preparation method among the above-mentioned discrimination method E.
4, the assay of berberine hydrochloride
Adopt high-efficient liquid phase technique to measure the content of the berberine hydrochloride in the medicine of the present invention, to improve quality determining method of the present invention:
1. proportion of mobile phase is preferred:
Respectively with 0.05mol/L NaH
2PO
4Buffer solution (H
3PO
4Transfer pH=3.0 ± 0.5)-the acetonitrile proportioning be that (60:25), (73:27), (80:35), (73:27) they are mobile phase, carry out assay, by comparing among the general figure of high-efficient liquid phase color the separating effect at each peak, determine preferred proportion of mobile phase, the result is as follows:
| Proportion of mobile phase | 60：19 | 73：27 | 80：35 | 85：43 |
| Each peak separating effect in the chromatogram | Very poor | Good | Difference | Very poor |
As can be seen from the above table, when proportion of mobile phase is 73:27, each peak good separation in the test sample chromatogram.
2. the methodological study of content assaying method
To the detection method of content that medicine of the present invention adopted, carried out related side's science of law from aspects such as linear relationship, stability, precision, repeatability, the response rate and investigated, concrete outcome is as follows:
(1) linear relationship is investigated and to be got reference substance solution (10 μ g/ml) and shake up, accurate respectively 2,4,6,8,10, the 12 μ l of absorption inject high performance liquid chromatograph, measure peak area, the results are shown in following table, and drawing standard curve, show that berberine hydrochloride is linear between 20ng-120ng, its regression equation is:
Area＝1.21984034*Amt—0.9256061(r＝0.99903)
(2) stability test reference substance solution respectively at preparing the back 0,2,4,6,12,24 hour, is measured in accordance with the law, and the result shows that it is basicly stable in 24 hours, the results are shown in following table
(3) the accurate need testing solution 10 μ l that draw of precision test repeat sample introduction 5 times, try to achieve relative standard deviation＜2%, the results are shown in following table
(4) the repeatability test is carried out mensuration 5 times to the preparation with a collection of medicine of the present invention, tries to achieve relative standard deviation＜2%, the results are shown in following table
(5) the recovery test precision take by weighing known content pharmaceutical preparation 0.25g of the present invention more respectively precision take by weighing berberine hydrochloride reference substance 0.25mg, press the preparation method operation of need testing solution, measure its content, and calculate its response rate, measurement result sees the following form:
From above result of the test as can be seen, its linear relationship of the content assaying method that medicine of the present invention adopted, stability, precision, repeatability etc. are all good, can effectively control drug quality of the present invention.
Following embodiment all can realize the described effect of above-mentioned experimental example
The specific embodiment
Embodiment 1
Radix Salviae Miltiorrhizae 115g, Herba Lycopi 70g, Semen Persicae 30g, Flos Carthami 180g, Radix Paeoniae Rubra 30g, Radix Angelicae Dahuricae 135g, Pericarpium Citri Reticulatae 75g, Rhizoma Alismatis 180g, Semen Vaccariae 115g, Herba Patriniae 280g, Fructus Toosendan 75g, Fructus Foeniculi (processed with salt) 135g, Cortex Phellodendri (processed with salt) 115g
This pharmaceutical composition adds conventional adjuvant, makes oral liquid by common process.
Embodiment 2
Radix Salviae Miltiorrhizae 125g, Herba Lycopi 65g, Semen Persicae 35g, Flos Carthami 165g, Radix Paeoniae Rubra 35g, Radix Angelicae Dahuricae 125g, Pericarpium Citri Reticulatae 75g, Rhizoma Alismatis 165g, Semen Vaccariae 125g, Herba Patriniae 265g, Fructus Toosendan 75g, Fructus Foeniculi (processed with salt) 125g, Cortex Phellodendri (processed with salt) 125g
This pharmaceutical composition adds conventional adjuvant, makes granule by common process.
Embodiment 3
Radix Salviae Miltiorrhizae 180g, Herba Lycopi 30g, Semen Persicae 70g, Flos Carthami 115g, Radix Paeoniae Rubra 70g, Radix Angelicae Dahuricae 75g, Pericarpium Citri Reticulatae 135g, Rhizoma Alismatis 115g, Semen Vaccariae 180g, Herba Patriniae 215g, Fructus Toosendan 135g, Fructus Foeniculi (processed with salt) 75g, Cortex Phellodendri (processed with salt) 180g
This pharmaceutical composition adds conventional adjuvant, makes granule by common process.
Embodiment 4
Radix Salviae Miltiorrhizae 165g, Herba Lycopi 35g, Semen Persicae 65g, Flos Carthami 125g, Radix Paeoniae Rubra 65g, Radix Angelicae Dahuricae 75g, Pericarpium Citri Reticulatae 125g, Rhizoma Alismatis 125g, Semen Vaccariae 165g, Herba Patriniae 225g, Fructus Toosendan 125g, Fructus Foeniculi (processed with salt) 75g, Cortex Phellodendri (processed with salt) 165g
This pharmaceutical composition adds conventional adjuvant, makes injection by common process.
Embodiment 5
Radix Salviae Miltiorrhizae 144g, Herba Lycopi 48g, Semen Persicae 48g, Flos Carthami 144g, Radix Paeoniae Rubra 48g, Radix Angelicae Dahuricae 96g, Pericarpium Citri Reticulatae 96g, Rhizoma Alismatis 144g, Semen Vaccariae 144g, Herba Patriniae 240g, Fructus Toosendan 96g, Fructus Foeniculi (processed with salt) 96g, Cortex Phellodendri (processed with salt) 144g
This pharmaceutical composition adds conventional adjuvant, makes tablet by common process.
Embodiment 6
Radix Salviae Miltiorrhizae 144g, Herba Lycopi 48g, Semen Persicae 48g, Flos Carthami 144g, Radix Paeoniae Rubra 48g, Radix Angelicae Dahuricae 96g, Pericarpium Citri Reticulatae 96g, Rhizoma Alismatis 144g, Semen Vaccariae 144g, Herba Patriniae 240g, Fructus Toosendan 96g, Fructus Foeniculi (processed with salt) 96g, Cortex Phellodendri (processed with salt) 144g
This pharmaceutical composition adds conventional adjuvant, makes capsule by common process.
Embodiment 7
Radix Salviae Miltiorrhizae 115g, Herba Lycopi 70g, Semen Persicae 30g, Flos Carthami 180g, Radix Paeoniae Rubra 30g, Radix Angelicae Dahuricae 135g, Pericarpium Citri Reticulatae 75g, Rhizoma Alismatis 180g, Semen Vaccariae 115g, Herba Patriniae 280g, Fructus Toosendan 75g, Fructus Foeniculi (processed with salt) 135g, Cortex Phellodendri (processed with salt) 115g
More than 13 the flavor, Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 6 times of amount 60% alcohol reflux 2 times, and each 2 hours, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 10 times of water gagings and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 2 times, add 8 times of water gagings for the first time and decoct 3 hours, add 6 times of water gagings for the second time and decoct 2 hours, collecting decoction filters, and filtrate and medicinal liquid merge, be condensed into 50 ℃ of relative densities and be 1.29 extractum, drying is ground into fine powder II, fine powder II adds fine powder I mixing, makes granule, drying, add volatile oil such as above-mentioned Fructus Foeniculi, add conventional adjuvant,, make the oral liquid of clinical acceptance through conventional method.
Embodiment 8
Radix Salviae Miltiorrhizae 125g, Herba Lycopi 65g, Semen Persicae 35g, Flos Carthami 165g, Radix Paeoniae Rubra 35g, Radix Angelicae Dahuricae 125g, Pericarpium Citri Reticulatae 75g, Rhizoma Alismatis 165g, Semen Vaccariae 125g, Herba Patriniae 265g, Fructus Toosendan 75g, Fructus Foeniculi (processed with salt) 125g, Cortex Phellodendri (processed with salt) 125g
More than 13 the flavor, Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 6 times of amount 60% alcohol reflux 2 times, and each 2 hours, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 10 times of water gagings and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 2 times, add 8 times of water gagings for the first time and decoct 3 hours, add 6 times of water gagings for the second time and decoct 2 hours, collecting decoction filters, and filtrate and medicinal liquid merge, be condensed into 50 ℃ of relative densities and be 1.29 extractum, drying is ground into fine powder II, fine powder II adds fine powder I mixing, makes granule, drying, add volatile oil such as above-mentioned Fructus Foeniculi, add conventional adjuvant,, make the granule of clinical acceptance through conventional method.
Embodiment 9
Radix Salviae Miltiorrhizae 180g, Herba Lycopi 30g, Semen Persicae 70g, Flos Carthami 115g, Radix Paeoniae Rubra 70g, Radix Angelicae Dahuricae 75g, Pericarpium Citri Reticulatae 135g, Rhizoma Alismatis 115g, Semen Vaccariae 180g, Herba Patriniae 215g, Fructus Toosendan 135g, Fructus Foeniculi (processed with salt) 75g, Cortex Phellodendri (processed with salt) 180g
More than 13 the flavor, Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 6 times of amount 60% alcohol reflux 2 times, and each 2 hours, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 10 times of water gagings and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 2 times, add 8 times of water gagings for the first time and decoct 3 hours, add 6 times of water gagings for the second time and decoct 2 hours, collecting decoction filters, and filtrate and medicinal liquid merge, be condensed into 50 ℃ of relative densities and be 1.29 extractum, drying is ground into fine powder II, fine powder II adds fine powder I mixing, makes granule, drying, add volatile oil such as above-mentioned Fructus Foeniculi, add conventional adjuvant,, make the pill of clinical acceptance through conventional method.
Embodiment 10
Radix Salviae Miltiorrhizae 165g, Herba Lycopi 35g, Semen Persicae 65g, Flos Carthami 125g, Radix Paeoniae Rubra 65g, Radix Angelicae Dahuricae 75g, Pericarpium Citri Reticulatae 125g, Rhizoma Alismatis 125g, Semen Vaccariae 165g, Herba Patriniae 225g, Fructus Toosendan 125g, Fructus Foeniculi (processed with salt) 75g, Cortex Phellodendri (processed with salt) 165g
More than 13 the flavor, Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 8 times of amount 50% alcohol reflux 3 times, and each 1 hour, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 10 times of water gagings and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 3 times, add 4 times of water gagings for the first time and decoct 4 hours, add 4 times of water gagings for the second time and decoct 4 hours, collecting decoction filters, and filtrate and medicinal liquid merge, be condensed into 50 ℃ of relative densities and be 1.29 extractum, drying is ground into fine powder II, fine powder II adds fine powder I mixing, makes granule, drying, add volatile oil such as above-mentioned Fructus Foeniculi, add conventional adjuvant,, make the tablet of clinical acceptance through conventional method.
Embodiment 11
Radix Salviae Miltiorrhizae 144g, Herba Lycopi 48g, Semen Persicae 48g, Flos Carthami 144g, Radix Paeoniae Rubra 48g, Radix Angelicae Dahuricae 96g, Pericarpium Citri Reticulatae 96g, Rhizoma Alismatis 144g, Semen Vaccariae 144g, Herba Patriniae 240g, Fructus Toosendan 96g, Fructus Foeniculi (processed with salt) 96g, Cortex Phellodendri (processed with salt) 144g
More than 13 the flavor, Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 4 times of amount 70% alcohol reflux 1 time, and each 3 hours, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 8 times of water gagings and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 3 times, add 4 times of water gagings at every turn and decoct collecting decoction 4 hours, filter, filtrate and medicinal liquid merging are condensed into 50 ℃ of relative densities and are 1.25 extractum, drying is ground into fine powder II, and fine powder II adds fine powder I mixing, make granule, drying adds volatile oil such as above-mentioned Fructus Foeniculi, adds conventional adjuvant, through conventional method, make the tablet of clinical acceptance.
Embodiment 12
Radix Salviae Miltiorrhizae 144g, Herba Lycopi 48g, Semen Persicae 48g, Flos Carthami 144g, Radix Paeoniae Rubra 48g, Radix Angelicae Dahuricae 96g, Pericarpium Citri Reticulatae 96g, Rhizoma Alismatis 144g, Semen Vaccariae 144g, Herba Patriniae 240g, Fructus Toosendan 96g, Fructus Foeniculi (processed with salt) 96g, Cortex Phellodendri (processed with salt) 144g
More than 13 the flavor, Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 8 times of amount 50% alcohol reflux 3 times, and each l hour, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 12 times of water gagings and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 1 time, add 10 times of water gagings at every turn and decoct collecting decoction 1 hour, filter, filtrate and medicinal liquid merge, and being condensed into 50 ℃ of relative densities is 1.35, be ground into fine powder II, fine powder II adds fine powder I mixing, makes granule, drying, add volatile oil such as above-mentioned Fructus Foeniculi, add conventional adjuvant,, make the granule of clinical acceptance through conventional method.
The method of quality control of embodiment 13 preparations of the present invention
Get embodiment 2 contents and carry out assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, and (it is 3.0 ± 0.5 that H3PO4 transfers pH)-acetonitrile is a mobile phase to the 0.05mol/L NaH2PO4 buffer solution of 73:27 ratio; The detection wavelength is 270nm; Number of theoretical plate is pressed the berberine hydrochloride peak and is calculated, and should be not less than 1500;
The preparation of reference substance solution: it is an amount of that the berberine hydrochloride reference substance decided in accurate title, adds methanol and make the solution that every 1ml contains 10 μ g;
The preparation of need testing solution: precision takes by weighing medicament composition granule agent .5g of the present invention, the accurate methanol 50ml that adds claims to decide weight, supersound process 30 minutes, put the cold weight that claims to decide again, supply the weight that subtracts mistake with methanol, shake up, leave standstill, get supernatant, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly;
Pharmaceutical composition per unit granule of the present invention contains Cortex Phellodendri in berberine hydrochloride C20H18ClNO4, must not be less than 0.10mg.
The method of quality control of embodiment 14 preparations of the present invention
Getting embodiment 10 differentiates:
Discrimination method: A, get 5 in pharmaceutical composition tablet of the present invention, remove sugar-coat, porphyrize, the 15ml that adds diethyl ether, jolting was extracted 5 minutes, filtered; Get filtrate 5ml, volatilize, residue adds 1 of 1% vanillin sulfuric acid solution, and drop edge is purple; Other gets filtrate 5ml, volatilize, residue add glacial acetic acid a little, make dissolving, add 1 in sulphuric acid again, slight fever, solution shows purple brown;
B, get 5 in pharmaceutical composition tablet of the present invention, remove sugar-coat, porphyrize adds ethanol 10ml, and jolting was extracted 10 minutes, filters, and filtrate adds magnesium powder a little and salt acid number to be dripped, and puts in the water-bath and heats, and it is red that solution shows;
C, to get pharmaceutical composition tablet of the present invention an amount of, removes sugar-coat, is ground into powder, take by weighing this powder 5g, add methanol 50ml supersound extraction half an hour, filter, filtrate is added on the 100-120 order, and 5g is on the neutral alumina post of internal diameter 10-15mm, with 40% methanol 50ml eluting, eluent evaporate to dryness, add water 15ml dissolving, aqueous solution water saturation n-butanol extraction twice, each 15ml merges n-butyl alcohol liquid, with the saturated washing twice of n-butyl alcohol, each 10ml; Discard water layer, n-butanol extracting liquid evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the Hesperidin reference substance, adds methanol and makes saturated solution, in contrast product; According to the thin layer chromatography test, draw above-mentioned reference substance 4 μ l, test sample 8 μ l, point sample is on same silica gel G plate respectively, lower floor's solution with the chloroform-methanol-water of 13:7:2 ratio is developing solvent, launches, and takes out, dry, spray places under the 365nm ultra-violet lamp and inspects with the aluminum chloride test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
D, get the peoniflorin reference substance in addition, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw reference substance, each 5 μ l of test sample among the discrimination method C, respectively point sample is on same silica gel G plate, is developing solvent with the chloroform-ethyl acetate-methanol-formic acid of 40:5:10:0.2 ratio, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, to get pharmaceutical composition tablet of the present invention an amount of, removes sugar-coat, is ground into powder, takes by weighing powder 0.3g, added methanol 10ml ultrasonic 5 minutes, filters, and evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 1 μ l of above-mentioned two kinds of solution, point sample is on same silica gel G plate respectively, benzene-ethyl acetate-isopropyl alcohol-methanol-strong ammonia solution with the 6:3:1.5:1.5:0.5 ratio is developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
The method of quality control of embodiment 15 preparations of the present invention
Getting embodiment 11 contents differentiates and assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, and (it is 3.0 ± 0.5 that H3PO4 transfers pH)-acetonitrile is a mobile phase to the 0.05mol/L NaH2PO4 buffer solution of 73:27 ratio; The detection wavelength is 270nm; Number of theoretical plate is pressed the berberine hydrochloride peak and is calculated, and should be not less than 1500;
The preparation of reference substance solution: it is an amount of that the berberine hydrochloride reference substance decided in accurate title, adds methanol and make the solution that every 1ml contains 10 μ g;
The preparation of need testing solution: precision takes by weighing pharmaceutical composition tablet 0.5g of the present invention, the accurate methanol 50ml that adds claims to decide weight, supersound process 30 minutes, put the cold weight that claims to decide again, supply the weight that subtracts mistake with methanol, shake up, leave standstill, get supernatant, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly;
Pharmaceutical composition per unit preparation of the present invention contains Cortex Phellodendri in berberine hydrochloride C20H18ClNO4, must not be less than 0.10mg;
Discrimination method: A, get 5 in pharmaceutical composition tablet of the present invention, remove sugar-coat, porphyrize, the 15ml that adds diethyl ether, jolting was extracted 5 minutes, filtered; Get filtrate 5ml, volatilize, residue adds 1 of 1% vanillin sulfuric acid solution, and drop edge is purple; Other gets filtrate 5ml, volatilize, residue add glacial acetic acid a little, make dissolving, add 1 in sulphuric acid again, slight fever, solution shows purple brown;
B, get 5 in pharmaceutical composition tablet of the present invention, remove sugar-coat, porphyrize adds ethanol 10ml, and jolting was extracted 10 minutes, filters, and filtrate adds magnesium powder a little and salt acid number to be dripped, and puts in the water-bath and heats, and it is red that solution shows;
C, to get pharmaceutical composition tablet of the present invention an amount of, removes sugar-coat, is ground into powder, take by weighing this powder 5g, add methanol 50ml supersound extraction half an hour, filter, filtrate is added on the 100-120 order, and 5g is on the neutral alumina post of internal diameter 10-15mm, with 40% methanol 50ml eluting, eluent evaporate to dryness, add water 15ml dissolving, aqueous solution water saturation n-butanol extraction twice, each 15ml merges n-butyl alcohol liquid, with the saturated washing twice of n-butyl alcohol, each 10ml; Discard water layer, n-butanol extracting liquid evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the Hesperidin reference substance, adds methanol and makes saturated solution, in contrast product; According to the thin layer chromatography test, draw above-mentioned reference substance 4 μ l, test sample 8 μ l, point sample is on same silica gel G plate respectively, lower floor's solution with the chloroform-methanol-water of 13:7:2 ratio is developing solvent, launches, and takes out, dry, spray places under the 365nm ultra-violet lamp and inspects with the aluminum chloride test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
D, get the peoniflorin reference substance in addition, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw reference substance, each 5 μ l of test sample among the discrimination method C, respectively point sample is on same silica gel G plate, is developing solvent with the chloroform-ethyl acetate-methanol-formic acid of 40:5:10:0.2 ratio, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, to get pharmaceutical composition tablet of the present invention an amount of, removes sugar-coat, is ground into powder, takes by weighing powder 0.3g, added methanol 10ml ultrasonic 5 minutes, filters, and evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 1 μ l of above-mentioned two kinds of solution, point sample is on same silica gel G plate respectively, benzene-ethyl acetate-isopropyl alcohol-methanol-strong ammonia solution with the 6:3:1.5:1.5:0.5 ratio is developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Embodiment 16
Radix Salviae Miltiorrhizae 144g Herba Lycopi 48g Semen Persicae 48g Flos Carthami 144g Radix Paeoniae Rubra 48g Radix Angelicae Dahuricae 96g Pericarpium Citri Reticulatae 96g Rhizoma Alismatis 144g Semen Vaccariae 144g Herba Patriniae 240g Fructus Toosendan 96g Fructus Foeniculi (processed with salt) 96g Cortex Phellodendri (processed with salt) 144g
More than 13 the flavor, Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder; Radix Salviae Miltiorrhizae, Fructus Toosendan add 6 times of amount 60% alcohol reflux secondaries, and each 2 hours, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 10 times of water gagings and extract volatile oil to most (about 4 hours), and the aqueous solution after distillation device is in addition collected; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water secondary, add 8 times of water gagings for the first time and decoct 3 hours, add 6 times of water gagings for the second time and decoct 2 hours, collecting decoction filters, and filtrate and above-mentioned medicinal liquid merge, being condensed into relative density is the extractum of 1.28～1.30 (50 ℃), and drying is ground into fine powder, add Rhizoma Alismatis, Radix Angelicae Dahuricae fine powder mixing, make granule, drying, add volatile oil such as above-mentioned Fructus Foeniculi, be pressed into 1000, sugar coating, promptly.
5 of this product are got in [discriminating] (1), remove sugar-coat, porphyrize, and the 15ml that adds diethyl ether, jolting was extracted 5 minutes, filtered; Get filtrate 5ml, volatilize, residue adds 1 of 1% vanillin sulfuric acid solution, and drop edge is purple; Other gets filtrate 5ml, volatilize, residue add glacial acetic acid a little, make dissolving, add 1 in sulphuric acid again, slight fever, solution shows purple brown.
(2) get 5 of this product, remove sugar-coat, porphyrize adds ethanol 10ml, and jolting was extracted 10 minutes, filters, and filtrate adds magnesium powder a little and salt acid number to be dripped, and puts in the water-bath and heats, and it is red that solution shows.
(3) it is an amount of to get this product, removes sugar-coat, is ground into powder, take by weighing this powder 5g, add methanol 50ml supersound extraction half an hour, filter, filtrate is added on the neutral alumina post (100-120 order, 5g, internal diameter 10-15mm), with 40% methanol 50ml eluting, eluent evaporate to dryness, add water 15ml dissolving, aqueous solution water saturation n-butanol extraction twice, each 15ml merges n-butyl alcohol liquid, with the saturated washing twice of n-butyl alcohol, each 10ml.Discard water layer, n-butanol extracting liquid evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution.Other gets the Hesperidin reference substance, adds methanol and makes saturated solution, in contrast product.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw above-mentioned reference substance 4 μ l, test sample 8 μ l, point sample is on same silica gel G plate respectively, lower floor's solution with chloroform-methanol-water (13:7:2) is developing solvent, launch, take out, dry, spray places under the ultra-violet lamp (365nm) and inspects with the aluminum chloride test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
(4) get the peoniflorin reference substance in addition, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw reference substance, differentiate each 5 μ l of test sample in (3), point sample is developing solvent with chloroform-ethyl acetate-methanol-formic acid (40:5:10:0.2) on same silica gel G plate respectively, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(5) it is an amount of to get this product, removes sugar-coat, is ground into powder, takes by weighing powder 0.3g, adds methanol 10ml ultrasonic 5 minutes, filters, and evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution.Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that 1ml contains 0.5mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 1 μ l of above-mentioned two kinds of solution, point sample is on same silica gel G plate respectively, with benzene-ethyl acetate-isopropyl alcohol-methanol-strong ammonia solution (6:3:1.5:1.5:0.5) is developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
[assay] measured according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica, 0.05mol/L NaH
2PO
4Buffer solution (H
3PO
4Transfer pH=3.0 ± 0.5)-acetonitrile (73:27) is a mobile phase; The detection wavelength is 270nm.Number of theoretical plate is pressed the berberine hydrochloride peak and is calculated, and should be not less than 1500.
It is an amount of that the berberine hydrochloride reference substance decided in the accurate title of the preparation of reference substance solution, adds methanol and make the solution that every 1ml contains 10 μ g.
The preparation precision of need testing solution takes by weighing this product 0.5g, and the accurate methanol 50ml that adds claims to decide weight, supersound process 30 minutes, put cold title again and decide weight, supply the weight that subtracts mistake, shake up, leave standstill with methanol, get supernatant, filter, get subsequent filtrate, promptly with microporous filter membrane (0.45 μ m).
Accurate respectively reference substance liquid, each the 10 μ l injection chromatograph of liquid of test sample liquid drawn of algoscopy measured, promptly.
Every of this product contains Cortex Phellodendri with berberine hydrochloride (C
20H
18ClNO
4) meter, must not be less than 0.10mg.
Embodiment 17
Radix Salviae Miltiorrhizae 115g, Herba Lycopi 70g, Semen Persicae 30g, Flos Carthami 180g, Radix Paeoniae Rubra 30g, Radix Angelicae Dahuricae 135g, Fructus Citri 75g, Rhizoma Alismatis 180g, Semen Vaccariae 115g, Herba Patriniae 280g, Fructus Toosendan 75g, Radix Linderae 135g, Cortex Phellodendri (processed with salt) 115g
This pharmaceutical composition adds conventional adjuvant, makes oral liquid by common process.
Embodiment 18
Radix Salviae Miltiorrhizae 125g, Herba Lycopi 65g, Semen Persicae 35g, Flos Carthami 165g, Radix Paeoniae Rubra 35g, Radix Angelicae Dahuricae 125g, Fructus Citri 75g, Rhizoma Alismatis 165g, Semen Vaccariae 125g, Herba Patriniae 265g, Fructus Toosendan 75g, Radix Linderae 125g, Cortex Phellodendri (processed with salt) 125g
This pharmaceutical composition adds conventional adjuvant, makes granule by common process.
Embodiment 19
Radix Salviae Miltiorrhizae 144g, Herba Lycopi 48g, Semen Persicae 48g, Flos Carthami 144g, Radix Paeoniae Rubra 48g, Radix Angelicae Dahuricae 96g, Fructus Citri 96g, Rhizoma Alismatis 144g, Semen Vaccariae 144g, Herba Patriniae 240g, Fructus Toosendan 96g, Radix Linderae 96g, Cortex Phellodendri (processed with salt) 144g
This pharmaceutical composition adds conventional adjuvant, makes tablet by common process.
Claims (10)
1. a pharmaceutical composition for the treatment of prostatic hyperplasia, urine retention is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Salviae Miltiorrhizae 100-200 weight portion, Herba Lycopi 20-80 weight portion, Semen Persicae 20-80 weight portion, Flos Carthami 100-200 weight portion, Radix Paeoniae Rubra 20-80 weight portion, Radix Angelicae Dahuricae 50-150 weight portion, Fructus Citri 50-150 weight portion, Rhizoma Alismatis 100-200 weight portion, Semen Vaccariae 100-200 weight portion, Herba Patriniae 200-300 weight portion, Fructus Toosendan 50-150 weight portion, Radix Linderae 50-150 weight portion, processed with salt Cortex Phellodendri 100-200 weight portion.
2. pharmaceutical composition for the treatment of prostatic hyperplasia, urine retention is characterized in that the crude drug of this pharmaceutical composition consists of:
Radix Salviae Miltiorrhizae 100-200 weight portion, Herba Lycopi 20-80 weight portion, Semen Persicae 20-80 weight portion, Flos Carthami 100-200 weight portion, Radix Paeoniae Rubra 20-80 weight portion, Radix Angelicae Dahuricae 50-150 weight portion, Rhizoma Alismatis 100-200 weight portion, Semen Vaccariae 100-200 weight portion, Herba Patriniae 200-300 weight portion, Fructus Toosendan 50-150 weight portion, processed with salt Cortex Phellodendri 100-200 weight portion Pericarpium Citri Reticulatae 50-150 weight portion, salt Fructus Foeniculi (processed) 50-150 weight portion.
3. pharmaceutical composition as claimed in claim 2 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Salviae Miltiorrhizae 100-130 weight portion, Herba Lycopi 60-80 weight portion, Semen Persicae 20-40 weight portion, Flos Carthami 160-200 weight portion, Radix Paeoniae Rubra 20-40 weight portion, Radix Angelicae Dahuricae 120-150 weight portion, Pericarpium Citri Reticulatae 50-80 weight portion, Rhizoma Alismatis 160-200 weight portion, Semen Vaccariae 100-130 weight portion, Herba Patriniae 260-300 weight portion, Fructus Toosendan 50-80 weight portion, salt Fructus Foeniculi (processed) 120-150 weight portion, processed with salt Cortex Phellodendri 100-130 weight portion.
4. a kind of pharmaceutical composition for the treatment of prostatic hyperplasia, urine retention as claimed in claim 3 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Salviae Miltiorrhizae 115 weight portions, Herba Lycopi's 70 weight portions, Semen Persicae 30 weight portions, Flos Carthami 180 weight portions, Radix Paeoniae Rubra 30 weight portions, the Radix Angelicae Dahuricae 135 weight portions, Pericarpium Citri Reticulatae 75 weight portions, Rhizoma Alismatis 180 weight portions, Semen Vaccariae 115 weight portions, Herba Patriniae 280 weight portions, Fructus Toosendan 75 weight portions, salt Fructus Foeniculi (processed) 135 weight portions, processed with salt Cortex Phellodendri 115 weight portions.
5. a kind of pharmaceutical composition for the treatment of prostatic hyperplasia, urine retention as claimed in claim 3 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Salviae Miltiorrhizae 125 weight portions, Herba Lycopi's 65 weight portions, Semen Persicae 35 weight portions, Flos Carthami 165 weight portions, Radix Paeoniae Rubra 35 weight portions, the Radix Angelicae Dahuricae 125 weight portions, Pericarpium Citri Reticulatae 75 weight portions, Rhizoma Alismatis 165 weight portions, Semen Vaccariae 125 weight portions, Herba Patriniae 265 weight portions, Fructus Toosendan 75 weight portions, salt Fructus Foeniculi (processed) 125 weight portions, processed with salt Cortex Phellodendri 125 weight portions.
6. a kind of pharmaceutical composition for the treatment of prostatic hyperplasia, urine retention as claimed in claim 2 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Salviae Miltiorrhizae 140-150 weight portion, Herba Lycopi 45-55 weight portion, Semen Persicae 45-55 weight portion, Flos Carthami 140-150 weight portion, Radix Paeoniae Rubra 45-55 weight portion, Radix Angelicae Dahuricae 90-110 weight portion, Pericarpium Citri Reticulatae 90-110 weight portion, Rhizoma Alismatis 140-150 weight portion, Semen Vaccariae 140-150 weight portion, Herba Patriniae 235-255 weight portion, Fructus Toosendan 90-110 weight portion, salt Fructus Foeniculi (processed) 90-110 weight portion, processed with salt Cortex Phellodendri 140-150 weight portion.
7. a kind of pharmaceutical composition for the treatment of prostatic hyperplasia, urine retention as claimed in claim 6 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Salviae Miltiorrhizae 144 weight portions, Herba Lycopi's 48 weight portions, Semen Persicae 48 weight portions, Flos Carthami 144 weight portions, Radix Paeoniae Rubra 48 weight portions, the Radix Angelicae Dahuricae 96 weight portions, Pericarpium Citri Reticulatae 96 weight portions, Rhizoma Alismatis 144 weight portions, Semen Vaccariae 144 weight portions, Herba Patriniae 240 weight portions, Fructus Toosendan 96 weight portions, salt Fructus Foeniculi (processed) 96 weight portions, processed with salt Cortex Phellodendri 144 weight portions.
8. as the arbitrary described a kind of preparation of drug combination method for the treatment of prostatic hyperplasia, urine retention of claim 2-7, it is characterized in that this method is: above 13 flavors, Rhizoma Alismatis, the Radix Angelicae Dahuricae are ground into fine powder I; Radix Salviae Miltiorrhizae, Fructus Toosendan add 4-8 and doubly measure the 50-70% alcohol reflux 1-3 time, and each 1-3 hour, merge extractive liquid, filtered, and reclaims ethanol; Fructus Foeniculi, Pericarpium Citri Reticulatae add 8-12 times of water gaging and extract volatile oil to most, the aqueous solution after the distillation, i.e. medicinal liquid device collection in addition; Seven flavor medicines such as medicinal residues and all the other Radix Paeoniae Rubra decoct with water 1-3 time, add 4-10 times of water gaging at every turn and decoct collecting decoction 1-4 hour, filter, filtrate and medicinal liquid merging are condensed into 50 ℃ of relative densities and are 1.20～1.40 extractum, drying is ground into fine powder II, and fine powder II adds fine powder I mixing, make granule, drying adds volatile oil such as above-mentioned Fructus Foeniculi, adds conventional adjuvant, through conventional method, make the preparation of clinical acceptance.
9. as the arbitrary described a kind of detection method for the treatment of the pharmaceutical composition of prostatic hyperplasia, urine retention of claim 2-7, it is characterized in that this method comprises one or more in following discrimination method and/or the assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, 50-90: the 0.05mol/L NaH of 10-50 ratio
2PO
4Buffer solution-acetonitrile is mobile phase, wherein H
3PO
4Transferring pH is 3.0 ± 0.5; The detection wavelength is 270nm; Number of theoretical plate is pressed the berberine hydrochloride peak and is calculated, and should be not less than 1500;
The preparation of reference substance solution: it is an amount of that the berberine hydrochloride reference substance decided in accurate title, adds methanol and make the solution that every 1ml contains 10 μ g;
The preparation of need testing solution: precision takes by weighing the accurate methanol 50ml that adds of the preparation content that is equivalent to crude drug content 1/600-1/800, claim to decide weight, supersound process 30 minutes is put cold title again and is decided weight, supplies the weight that subtracts mistake with methanol, shake up, leave standstill, get supernatant, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly;
Pharmaceutical composition per unit preparation contains Cortex Phellodendri with berberine hydrochloride C
20H
18ClNO
4Meter must not be less than 0.10mg;
Discrimination method: A, get the preparation content that is equivalent to crude drug content 1/100-1/300, remove sugar-coat, porphyrize, the 15ml that adds diethyl ether, jolting was extracted 5 minutes, filtered; Get filtrate 5ml, volatilize, residue adds 1 of 1% vanillin sulfuric acid solution, and drop edge is purple; Other gets filtrate 5ml, volatilize, residue add glacial acetic acid a little, make dissolving, add 1 in sulphuric acid again, slight fever, solution shows purple brown;
B, get the preparation content that is equivalent to crude drug content 1/100-1/300, remove sugar-coat, porphyrize adds ethanol 10ml, and jolting was extracted 10 minutes, filters, and filtrate adds magnesium powder a little and salt acid number to be dripped, and puts in the water-bath and heats, and it is red that solution shows;
C, the compositions preparation of getting it filled are an amount of, remove sugar-coat, are ground into powder, take by weighing the powder that is equivalent to crude drug content 1/50-1/80, add methanol 50ml supersound extraction half an hour, filter, filtrate is added on the 100-120 order, and 5g is on the neutral alumina post of internal diameter 10-15mm, with 40% methanol 50ml eluting, eluent evaporate to dryness, add water 15ml dissolving, aqueous solution water saturation n-butanol extraction twice, each 15ml merges n-butyl alcohol liquid, with the saturated washing twice of n-butyl alcohol, each 10ml; Discard water layer, n-butanol extracting liquid evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the Hesperidin reference substance, adds methanol and makes saturated solution, in contrast product; Test according to thin layer chromatography, draw above-mentioned reference substance 4 μ l, test sample 8 μ l, point sample is on same silica gel G plate respectively, with 5-25: 5-15: lower floor's solution of the chloroform-methanol-water of 1-3 ratio is developing solvent, launch, take out, dry, spray places under the 365nm ultra-violet lamp and inspects with the aluminum chloride test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
D, get the peoniflorin reference substance in addition, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw reference substance, each 5 μ l of test sample among the discrimination method C, respectively point sample is on same silica gel G plate, and with 20-60: 1-10: 5-15: the chloroform-ethyl acetate of 0.1-0.3 ratio-methanol-formic acid is developing solvent, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, the compositions preparation of getting it filled are an amount of, remove sugar-coat, are ground into powder, take by weighing the powder that is equivalent to crude drug content 1/3500-1/700, add methanol 10ml ultrasonic 5 minutes, filter, and evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 1 μ l of above-mentioned two kinds of solution, point sample is on same silica gel G plate respectively, with 4-8: 1-5: 0.5-2.5: 0.5-2.5: the benzene-ethyl acetate of 0.1-1.0 ratio-isopropyl alcohol-methanol-strong ammonia solution is developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
10. a kind of detection method for the treatment of the pharmaceutical composition of prostatic hyperplasia, urine retention as claimed in claim 9 is characterized in that this method comprises one or more in following discrimination method and/or the assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler, the 0.05mol/LNaH of 73: 27 ratios
2PO
4Buffer solution-acetonitrile is mobile phase, wherein H
3PO
4Transferring pH is 3.0 ± 0.5; The detection wavelength is 270nm; Number of theoretical plate is pressed the berberine hydrochloride peak and is calculated, and should be not less than 1500;
The preparation of reference substance solution: it is an amount of that the berberine hydrochloride reference substance decided in accurate title, adds methanol and make the solution that every 1ml contains 10 μ g;
The preparation of need testing solution: precision takes by weighing the preparation content that is equivalent to crude drug content 1/700, the accurate methanol 50ml that adds claims to decide weight, supersound process 30 minutes, put the cold weight that claims to decide again, supply the weight that subtracts mistake with methanol, shake up, leave standstill, get supernatant, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly;
Pharmaceutical composition per unit preparation contains Cortex Phellodendri with berberine hydrochloride C
20H
18ClNO
4Meter must not be less than 0.10mg;
Discrimination method: A, get the preparation content that is equivalent to crude drug content 1/200, remove sugar-coat, porphyrize, the 15ml that adds diethyl ether, jolting was extracted 5 minutes, filtered; Get filtrate 5ml, volatilize, residue adds 1 of 1% vanillin sulfuric acid solution, and drop edge is purple; Other gets filtrate 5ml, volatilize, residue add glacial acetic acid a little, make dissolving, add 1 in sulphuric acid again, slight fever, solution shows purple brown;
B, get the preparation content that is equivalent to crude drug content 1/200, remove sugar-coat, porphyrize adds ethanol 10ml, and jolting was extracted 10 minutes, filters, and filtrate adds magnesium powder a little and salt acid number to be dripped, and puts in the water-bath and heats, and it is red that solution shows;
C, the compositions preparation of getting it filled are an amount of, remove sugar-coat, are ground into powder, take by weighing the powder that is equivalent to crude drug content 1/70, add methanol 50ml supersound extraction half an hour, filter, filtrate is added on the 100-120 order, and 5g is on the neutral alumina post of internal diameter 10-15mm, with 40% methanol 50ml eluting, eluent evaporate to dryness, add water 15ml dissolving, aqueous solution water saturation n-butanol extraction twice, each 15ml merges n-butyl alcohol liquid, with the saturated washing twice of n-butyl alcohol, each 10ml; Discard water layer, n-butanol extracting liquid evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the Hesperidin reference substance, adds methanol and makes saturated solution, in contrast product; According to the thin layer chromatography test, draw above-mentioned reference substance 4 μ l, test sample 8 μ l, point sample is on same silica gel G plate respectively, lower floor's solution with the chloroform-methanol-water of 13: 7: 2 ratios is developing solvent, launches, and takes out, dry, spray places under the 365nm ultra-violet lamp and inspects with the aluminum chloride test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
D, get the peoniflorin reference substance in addition, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw reference substance, each 5 μ l of test sample among the discrimination method C, point sample is on same silica gel G plate, with 40: 5: 10 respectively: the chloroform-ethyl acetate of 0.2 ratio-methanol-formic acid is developing solvent, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, the compositions preparation of getting it filled are an amount of, remove sugar-coat, are ground into powder, take by weighing the powder that is equivalent to crude drug content 3/3500, add methanol 10ml ultrasonic 5 minutes, filter, and evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution; Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 1 μ l of above-mentioned two kinds of solution, point sample is on same silica gel G plate respectively, with 6: 3: 1.5: the benzene-ethyl acetate of 1.5: 0.5 ratios-isopropyl alcohol-methanol-strong ammonia solution was developing solvent, put in the saturated expansion cylinder of ammonia solution, launch, take out, dry, place under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2007100640633A CN101254260B (en) | 2007-02-26 | 2007-02-26 | Pharmaceutical combination for curing prostate gland hyperplasy, anuresis and preparation thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100640633A CN101254260B (en) | 2007-02-26 | 2007-02-26 | Pharmaceutical combination for curing prostate gland hyperplasy, anuresis and preparation thereof |
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| CN 201010576804 Division CN102028828B (en) | 2007-02-26 | 2007-02-26 | Medical composite for treating benign prostatic hyperplasia and urodialysis and detection method of medical composite |
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| CN101254260B true CN101254260B (en) | 2011-02-09 |
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| CN102028828B (en) * | 2007-02-26 | 2013-03-27 | 北京亚东生物制药有限公司 | Medical composite for treating benign prostatic hyperplasia and urodialysis and detection method of medical composite |
| CN102716184A (en) * | 2012-07-02 | 2012-10-10 | 苏州纳晶医药技术有限公司 | Chinese medicinal composition and application thereof |
| CN106353446B (en) * | 2016-08-12 | 2020-06-23 | 上海黄海制药有限责任公司 | Annian granule identification and content determination method |
| CN110068647A (en) * | 2019-05-29 | 2019-07-30 | 四川新绿色药业科技发展有限公司 | A kind of thin-layer identification method of citron granule |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1362142A (en) * | 2001-01-05 | 2002-08-07 | 杨孟君 | Nano Niaosaitong medicine for dredging urethra and its preparation |
| CN1742903A (en) * | 2005-09-29 | 2006-03-08 | 济南宏济堂制药有限责任公司 | Medicine for treating prostatitis and hyperlasia of prostate |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1362142A (en) * | 2001-01-05 | 2002-08-07 | 杨孟君 | Nano Niaosaitong medicine for dredging urethra and its preparation |
| CN1742903A (en) * | 2005-09-29 | 2006-03-08 | 济南宏济堂制药有限责任公司 | Medicine for treating prostatitis and hyperlasia of prostate |
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