CN1923270A - Medicine for treating benign prostate hyperplasia and method of prepn. of the same - Google Patents

Abstract

The invention relates to a medicinal preparation for treating benign prostate hyperplasia and process for its preparation, wherein the medicament is prepared from astragalus root, peach kernels, zedoary, rhubarb horsetails, poria cocos, coix seed, motherwort, selfheal, Cinnamomum cassia, root of ballon flower, subprostrate sophora root, achyranthes and cyathula root, and medicinal auxiliary materials.

Description

Medicine of treatment benign prostate hyperplasia and preparation method thereof

Technical field

What the present invention relates to is compound Chinese medicinal preparation and preparation method thereof, specifically is a kind of medicine for the treatment of benign prostate hyperplasia and preparation method thereof, and the name of this medicine is called HuangCurcuma Tong and closes capsule.

Background technology

Prostate is made up of body of gland and muscle, and these tissues can be with age-growth.Their overgrowth will cause benign prostatic hyperplasia.Because the increase of prostata tissue causes the extruding to urethra, thereby causes dysuria.Along with rhythm of life is constantly accelerated, Benign Prostatic Hypertrophy day by day increases, and according to data, Benign Prostatic Hypertrophy has the rejuvenation of being development trend.Benign prostatic hyperplasia is not a cancer, can not change into cancer yet; The optimum poor growth of these prostate bodies of gland and can not be diffused into the health other parts.Yet these two kinds of diseases may simultaneously and be deposited.Modern medicine study thinks, benign prostatic hyperplasia be by the androgen dihydrotestosterone activity cause.Testosterone is the main androgen of male, under the effect of enzyme, becomes two hydrogen testosterones, and two hydrogen testosterones are active hormones that androgen stimulates prostatic hyperplasia.Estrogen also has certain influence to prostatic hyperplasia.The symptom performance is 1. frequent micturitions, urgent micturition: modal symptom is a frequent micturition, and increases the weight of gradually, especially the nocturia increased frequency.2. carrying out property dysuria: mainly shown as urine slowly, trouble urinating, it is unable to penetrate urine, the urine line is tiny, urine drip drop, segmentation is urinated and is urinated and waits not to the utmost.3. urinary incontinence.4. acute urinary retention: if any suffer from cold, drink, inducement such as fatigue and when causing body of gland and bladder neck congestion and edema, acute urinary retention can take place.Patient's bladder extreme expansion, pain, urine meaning is frequent, and is toss about and feel uneasy, be difficult to fall asleep.5. hematuria: amount of bleeding does not wait and mostly is intermittent, and idol is bled profusely, and clot is full of bladder, must emergent management.6. renal insufficiency symptom: go down owing to the long-term urokinase road-blockage causes two renal functioies late period, shows as inappetence, feels sick, vomiting and anemia etc.7. other symptoms: increasing abdominal pressure and urinate owing to long-term dysuria relies on, can cause or increase the weight of diseases such as hemorrhoid, proctoptosis, is the commonly encountered diseases of male's Urology Surgery.

Summary of the invention

The object of the present invention is to provide a kind of medicine for the treatment of benign prostate hyperplasia.

Another object of the present invention provides a kind of preparation method for the treatment of the medicine of benign prostate hyperplasia.

The present invention is implemented by following scheme.

The prostatic hyperplasia clinical manifestation is not smooth for urine, and a large amount is few frequently, even urine retention is obstructed, belongs to the category of the traditional Chinese medical science " difficulty in urination " disease, and theory of Chinese medical science thinks that the cause of disease of the difficulty in urination is many-sided: or because of damp and hot retardance bladder, functioning of bladder is unfavorable; Or fall because of lung qi loses in respectful, water channel is logical transfer unfavorable; Or because of deficiency-weakness of spleen-QI, clear QI failing to ascend, turbid QI failing to descend; Or because of depression of liver-QI, qiactivity of triple energizer loses power; Or because of a little less than the deficiency of kidney-QI, it is too late to gasify; Or because of losing smart the obstruction, the obstructed grade of water channel influences the gasification of bladder, due to folding is unfavorable.The difficulty in urination due to the different causes of disease often causes further that in the advancing of disease process blood clots absorbing stagnates, i.e. so-called " pathogen usually intruding into collateral in protracted disease ".The blood stasis bladder, functioning of bladder is unfavorable, and water channel is not smooth, closes so go out the obstructed stasis of blood of urine retention even the urine drop occurs.

We's difficulty in urination syndrome characteristics of controlling are formulated in conjunction with clinical experience.With the Radix Astragali, Semen Persicae is monarch drug, the sweet temperature of the Radix Astragali, goes into spleen, lung meridian, is the key medicine of QI invigorating, and invigorating the spleen and replenishing QI, merit that the lucid yang sending up is turbid are arranged, and Radix Astragali QI invigorating, promote blood capable, with the dissipation blood stasis; Semen Persicae, bitter sweet and flat, go into urinary bladder channel, blood circulation promoting and blood stasis dispelling, the stasis of blood of the bladder of being good at especially dispelling.Rhizoma Curcumae, Radix Et Rhizoma Rhei, Rhizoma Smilacis Glabrae, Semen Coicis, Herba Leonuri, Spica Prunellae are ministerial drug, Rhizoma Curcumae promoting flow of QI and blood wherein, Radix Et Rhizoma Rhei blood circulation promoting and blood stasis dispelling, Rhizoma Smilacis Glabrae eliminating damp-heat, the Semen Coicis clearing away liver-fire has QI invigorating in the QI invigorating, Semen Coicis invigorating the spleen and benefiting QI, promoting diuresis with drugs of tasteless flavour, the Herba Leonuri activating blood and promoting diuresis, Spica Prunellae clearing away liver-fire, dissipating blood stasis knot.Cortex Cinnamomi, Radix Platycodonis, Rhizoma Menispermi are adjuvant drug.Rhizoma Menispermi is if cold help the heat of Rhizoma Smilacis Glabrae with the removing summer-heat bladder, and the product that Cortex Cinnamomi is warm have the too fraud of bitter cold of the Spica Prunellae of controlling, Radix Et Rhizoma Rhei, Rhizoma Menispermi Rhizoma Smilacis Glabrae, injure one's stomach in case bitter cold is too decreased sun, and Cortex Cinnamomi has the effect of promoting blood circulation again, to assist monarch-minister drug with blood stasis dispelling.Lung is that water makes, and Radix Achyranthis Bidentatae is invigorated blood circulation and be can priming descending, makes medicine act on disease institute, so for making, be equipped with the medically acceptable all kinds of preparations that pharmaceutic adjuvant is formed again.Whole prescription has the effect of benefiting QI for activating blood circulation, eliminating damp-heat.

The weight proportion of its each active ingredient can for:

Radix Astragali 5%-20% Semen Persicae 2%-15% Rhizoma Curcumae 0%-10%

Radix Et Rhizoma Rhei 0%-5% Rhizoma Smilacis Glabrae 1%-15% Semen Coicis 2%-30%

Herba Leonuri 2%-20% Spica Prunellae 1%-20% Cortex Cinnamomi 0%-10%

Radix Platycodonis 0%-10% Rhizoma Menispermi 0%-10%.Radix Cyathulae 0%-10%.

The weight proportion of each active ingredient also can for:

Radix Astragali 7%-18% Semen Persicae 2%-15% Rhizoma Curcumae 3%-10%

Radix Et Rhizoma Rhei 0%-3% Rhizoma Smilacis Glabrae 5%-15% Semen Coicis 10%-30%

Herba Leonuri 5%-20% Spica Prunellae 5%-20% Cortex Cinnamomi 3%-10%

Radix Platycodonis 3%-10% Rhizoma Menispermi 3%-10%.Radix Cyathulae 3%-10%.

The weight proportion of each active ingredient can also for:

The Radix Astragali 11.63% Semen Persicae 6.97% Rhizoma Curcumae 6.97%

Radix Et Rhizoma Rhei 0.78% Rhizoma Smilacis Glabrae 9.30% Semen Coicis 15.50%

Herba Leonuri 11.63% Spica Prunellae 11.63% Cortex Cinnamomi 4.65%

Radix Platycodonis 6.97% Rhizoma Menispermi 6.97%.Radix Cyathulae 6.97%.

The Chinese crude drug source of being mentioned in the above-mentioned prescription is as follows:

The Radix Astragali: be the dry root of leguminous plant Radix Astagali Astragalus membranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao or Radix Astragali Astragalus membranaceus (Fisch.) Bge..

Semen Persicae: be the dry mature seed of rosaceous plant peach Prunus persica (L.) Batsch or mountain peach Prunusdavidiana (Carr.) Franch..

Rhizoma Curcumae: be the dry rhizome of zingiberaceous plant Rhizoma Curcumae Curcuma phaeocaulis Val., Guangxi zedoary Curcuma kwangsiensis S.G.Lee et C.F.Liang or RADIX CURCUMAE Curcumawengyujin Y.H.Chen et C.Ling.

Radix Et Rhizoma Rhei: be the dry root and rhizome of polygonum rheum palmatum Rheum palmatum L., Rheum tanguticum Rhuemtangguticum Maxim.ex Balf. or Rheum officinale Rheum officinale Baill..

Rhizoma Smilacis Glabrae: be the dry rhizome of liliaceous plant smilacis glabra Smilax glabra Roxb..

Semen Coicis: be the dry mature kernal of grass Semen Coicis Coix lacryma-jobiL.var.ma-yuen (Roman.).

Herba Leonuri: be the fresh or dry aerial parts of labiate Herba Leonuri leonurus japonicus Houtt..

Spica Prunellae: be the dry fruit ear of labiate Spica Prunellae Prunella vulgaris L..

Cortex Cinnamomi: be the dry bark of canella Cortex Cinnamomi Cinnamomum cassia Presl.

Rhizoma Menispermi: be the dry rhizome of menispermaceous plants Caulis menispermi Menispermum dauricum DC..

Radix Platycodonis: be the dry root of campanulaceae Platycodon grandiflouorum Platycodon grandiflorum (Jacq.) A.DC..

Radix Cyathulae: be the dry root of amaranthaceous plant Radix Cyathulae Cyathula officimalis Kuan.

Prescription can be through the conventional extractive technique such as the direct grounds travel of this area, put forward technologies such as volatile oil, water extract-alcohol precipitation, alcohol extracting-water precipitating produces active ingredient as the medicine of treatment benign prostate hyperplasia.Again described active ingredient and medically acceptable carrier or excipient composition are made various pharmaceutical formulations such as capsule, tablet, granule, pill, powder, syrup, oral liquid etc.And wherein said medically acceptable carrier or excipient (being pharmaceutic adjuvant) are to select to use according to different dosage forms.

One of preparation method of the medicine of above-mentioned treatment benign prostate hyperplasia, it mainly comprises following process steps:

(1) takes by weighing raw material by the said ratio amount;

(2) get the Semen Coicis of recipe quantity Cortex Cinnamomi, Radix Et Rhizoma Rhei and 10%-50%, the Semen Persicae of 5%-30%, mixed powder is broken into fine powder;

(3) Rhizoma Curcumae water vapour distillation volatile oil, the aqueous solution packaging container is standby, and medicinal residues are retained, and get volatile oil, use the beta-schardinger dextrin-inclusion, get inclusion complex;

(4) Radix Astragali decocting extracts secondary or more than the secondary, collecting decoction filters, and is concentrated into the thick paste shape, takes out, and puts coldly, adds the ethanol acclimatization, places, filter, ethanol liquid;

(5) Yu Xia Semen Persicae, Semen Coicis add the decoction pieces of Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts secondary or more than the secondary, collecting decoction, be concentrated into the thick paste shape, it is an amount of to add ethanol, leave standstill, filter, the ethanol liquid of the filtrate and the aforementioned Radix Astragali merges, reclaim ethanol, and being condensed into the thick paste shape, drying under reduced pressure gets dry extract, pulverize, sieve, the fine powder mixing of medicines such as the beta-cyclo dextrin included compound fine powder of adding Rhizoma Curcumae volatile oil and above-mentioned Cortex Cinnamomi is equipped with pharmaceutic adjuvant and makes medically acceptable all kinds of preparations.

And the water vapour distillation time described in the step (3) can be 6-10 hour.

Beta-schardinger dextrin-consumption described in the step (3) can be that the 3-10 of volatile oil doubly measures.

The each amount of water of Radix Astragali decocting described in the step (4) can be 4-10 times, decocting time can be 1-3 hour, thick paste density is 1.05-1.35 (70 ℃ of surveys), and ethanol content can be to reach 40%-80% when adding ethanol precipitation, and time of repose can be 6-48 hour.

The described decocting of step (5) adds water at every turn can be 4-10 times, and decocting time can be 1-3 hour, and thick paste density is 1.05-1.35 (70 ℃ of surveys), and ethanol content can reach 40%-80% when adding ethanol precipitation, and can be 6-48 hour standing time.

Drying under reduced pressure can be at＜80 ℃ in the step (5), and sieving is the 30-80 order.

The medicine of treatment benign prostate hyperplasia of the present invention can obviously suppress the inductive prostata tissue hypertrophy of testosterone, significantly reduces the weight in wet base and the dry weight of each leaf of prostate.Alleviate the dysuria symptom, reduce the nocturia number of times, improve urine flow rate parameter, reduce residual urine volume, and do not have the overt toxicity effect, safe and reliable; Its preparation method process route is selected rationally, the bioavailability height, and good drug efficacy, steady quality is easy to control;

Following research conclusions such as pharmacodynamics further illustrate beneficial effect of the present invention.

Main pharmacodynamics research and conclusion

Treatment experiment by to old dog benign prostatic hyperplasia illustrates that per os gives HuangCurcuma Tong and closes capsule, can make the prostate volume of prostatic hyperplasia dog dwindle 34.8% (2g/Kg days).Prostate/body weight ratio reduces, and RNA and dna content reduce in the prostata tissue, and glandular lobule diminishes, the relative broadening of stroma, and prostata tissue does/and wet ratio is and increases trend.To the dog body weight, each main organs gastrointestinal mucosa and testis spermatogenic cell etc. are not seen obvious influence, are 1g/Kg to the prostatic inhibiting effective dose of dog, do not have tangible graded effect relation.

Observe (oral administration 30 days by treatment to rat prostate hypertrophy disease model, dosage is 1.6g, 3.6g, 7.2g crude drug/Kg (quite clinical day dosing 3,7,14 times)), illustrate that this medicine can obviously suppress the inductive rat prostate hamartoplasia of testosterone, be embodied in and obviously reducing prostatic volume, the weight in wet base and the weight in wet base/body weight ratio of each leaf of reduction prostate.Between rat prostate hypertrophy three dosage that cause for testosterone propionate certain dose-effect relationship is arranged.Especially remarkable with senior middle school's dosage drug effect, and rat body weight does not have influence, is better than positive control Chinese medicine, similar to the diethylstilbestrol positive control drug.Rat prostate there is the effect that reduces its cyclomastopathy growth.Medication group prostate lobule obviously reduces, and with matched group notable difference is arranged.The mechanism of action is the inhibitory action to prostatic epithelium.In addition by a series of experiments, find the concentration 10 minutes of 10mg/ml, can 100% ground remove blood capillary spasm because of going methylepinephrine to cause, but not too obvious to the variation of little blood flow; But the vascular smooth muscle due on 10-30mg/ml dosage-dependency ground diastole first kidney shrinks; 10mg, 20mg/m1 have inhibitory action to the inductive platelet aggregation of ADP.

By the rough film of dog cortex is carried out radioligand in conjunction with test, illustrated that logical the closing of yellow cowherb of different trials presents concentration dependent inhibition 125 _IBEWith α ₁Receptors bind shows as the obvious therapeutic action of benign prostatic hyperplasia patient symptom clinically.

Toxicological study and conclusion

By the maximum resistance test of chmice acute per os is 139.59g crude drug/Kg body weight (291 of quite clinical day dosing.1 times) any toxic reaction and death do not appear.

Long term toxicity test, rat is oral 23.0,11.5,5.7Gtg medicine/Kg (quite 48 times, 24 times, 12 times of adult's dosage) is after 90 days, the general situation of rat, body weight gain, edible consumption rate, hemogram, urine examination, ten serum biochemistry index testing results, and organ coefficient and histopathologic examination, there is no the overt toxicity reaction, and there was no significant difference between the blank group only has 3.0g crude drug/Kg to organize body weight gain slowly in matched group, but no difference of science of statistics.Illustrated that the clinical practice of this medicine has big safety.

The specific embodiment

The present invention is further illustrated below in conjunction with embodiment, and following each embodiment only is used to illustrate the present invention, but to not restriction of the present invention.

Embodiment one

The preparation of capsule

Take by weighing by recipe quantity: Radix Astragali 300g, Semen Persicae 180g, Rhizoma Curcumae 180g, Radix Et Rhizoma Rhei 20g, Rhizoma Smilacis Glabrae 240g, Semen Coicis 400g, Herba Leonuri 300g, Spica Prunellae 300g, Cortex Cinnamomi 120g, Radix Platycodonis 180g, Rhizoma Menispermi 180g, Radix Cyathulae 180g.

Get Cortex Cinnamomi, Radix Et Rhizoma Rhei, Semen Coicis (50% is 200g), Semen Persicae (5% is 9g), mixed powder is broken into fine powder; Rhizoma Curcumae extracted volatile oil 8 hours with steam distillation, and the aqueous solution packaging container is standby, and medicinal residues are retained.Get volatile oil,, get inclusion complex with 6 times of amount beta-schardinger dextrin-inclusions; Radix Astragali decocting extracts three times, adds 8 times in water at every turn, decocts 1.5 hours, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 60%, places 24 hours, and filtration gets ethanol liquid; Remaining Semen Persicae (171g), Semen Coicis (200g) adds the Rhizoma Smilacis Glabrae of foreign side's amount, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts secondary, adds 8 times of amounts of water at every turn, decocted 1.5 hours, and merged decocting liquid twice, and merge with the Rhizoma Curcumae aqueous solution, filter, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts cold, add ethanol, make ethanol content reach 60%, placed 24 hours, filter, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and be condensed into thick paste, drying under reduced pressure (＜70 ℃), get dry extract, pulverize, cross 80 mesh sieves, the fine powder that adds medicines such as the beta-cyclo dextrin included compound fine powder of Rhizoma Curcumae volatile oil and above-mentioned Cortex Cinnamomi is with an amount of dextrin mixing, with ethanol system, drying is encapsulatedly made 1000, promptly.

Embodiment two

Take by weighing by recipe quantity: Radix Astragali 310g, Semen Persicae 200g, Rhizoma Curcumae 190g, Radix Et Rhizoma Rhei 20g, Rhizoma Smilacis Glabrae 250g, Semen Coicis 400g, Herba Leonuri 310g, Spica Prunellae 300g, Radix Platycodonis 152g, Cortex Cinnamomi 0g, Rhizoma Menispermi 258g, Radix Cyathulae 190g.

Get Cortex Cinnamomi, Radix Et Rhizoma Rhei, Semen Coicis 50% (being 200g), Semen Persicae 5% (being 10g) mixed powder and be broken into fine powder; The Rhizoma Curcumae decoction pieces extracted volatile oil 6 hours with steam distillation, and the aqueous solution packaging container is standby, and medicinal residues are retained.Get volatile oil,, get inclusion complex with 5 times of amount beta-schardinger dextrin-inclusions; Radix Astragali decocting extracts three times, adds 6 times in water at every turn, decocts 1 hour, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 40%, places 18 hours, and filtration gets ethanol liquid; Remaining Semen Persicae 190g, Semen Coicis 200g adds the Rhizoma Smilacis Glabrae of recipe quantity, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, the decoction pieces of Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts three times, adds 6 times of amounts of water at every turn, decocted 1 hour, and merged decocting liquid twice, and merge with the Rhizoma Curcumae aqueous solution, filter, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts cold, add ethanol, make ethanol content reach 60%, placed 30 hours, filter, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and be condensed into thick paste, drying under reduced pressure (＜80 ℃), get dry extract, pulverize, cross 70 mesh sieves, the fine powder that adds medicines such as the beta-cyclo dextrin included compound fine powder of Rhizoma Curcumae volatile oil and above-mentioned Cortex Cinnamomi is with an amount of dextrin mixing, with ethanol system, drying is encapsulatedly made 1000, promptly.

Embodiment three

The preparation of tablet

Take by weighing by recipe quantity: Radix Astragali 516g, Semen Persicae 51.6g, Rhizoma Curcumae 258g, Radix Et Rhizoma Rhei 0g, Rhizoma Smilacis Glabrae 77.4g, Semen Coicis 619.2g, Herba Leonuri 129g, Spica Prunellae 516g, Cortex Cinnamomi 206.4g, Radix Platycodonis 77.4g, Rhizoma Menispermi 51.6g, Radix Cyathulae 77.4g.

Get Cortex Cinnamomi, Radix Et Rhizoma Rhei, Semen Coicis 61.92g, Semen Persicae 15.48g mixed powder and be broken into fine powder; The Rhizoma Curcumae decoction pieces extracted volatile oil 8 hours with steam distillation, and the aqueous solution packaging container is standby, and medicinal residues are retained.Get volatile oil,, get inclusion complex with 7 times of amount beta-schardinger dextrin-inclusions; Radix Astragali decocting extracts three times, adds 10 times in water at every turn, decocts 3 hours, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 80%, places 48 hours, and filtration gets ethanol liquid; Remaining Semen Persicae, the Rhizoma Smilacis Glabrae of Semen Coicis and recipe quantity, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, the decoction pieces of Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts secondary, adds 10 times of amounts of water at every turn, decocted 2 hours, merge decocting liquid twice, and merge, filter with the Rhizoma Curcumae aqueous solution, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), take out, put coldly, add ethanol, make ethanol content reach 60%, placed 20 hours, and filtered, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and being condensed into thick paste, drying under reduced pressure (＜70 ℃) gets dry extract, pulverize, cross 60 mesh sieves, the fine powder of medicines such as the beta-cyclo dextrin included compound fine powder of adding Rhizoma Curcumae volatile oil and above-mentioned Cortex Cinnamomi adds an amount of excipient mixing, tabletting is made 1000, promptly.

Embodiment four

Take by weighing by recipe quantity: Radix Astragali 516g, Semen Persicae 51.6g, Rhizoma Curcumae 258g, Radix Et Rhizoma Rhei 0g, Rhizoma Smilacis Glabrae 129g, Semen Coicis 774g, Herba Leonuri 51.6g, Spica Prunellae 387g, Cortex Cinnamomi 258g, Rhizoma Menispermi 77.4g, Radix Cyathulae 77.4g.

Get Cortex Cinnamomi, Radix Et Rhizoma Rhei, Semen Coicis 77.4g, Semen Persicae 15.48g mixed powder and be broken into fine powder; The Rhizoma Curcumae decoction pieces extracted volatile oil 10 hours with steam distillation, and the aqueous solution packaging container is standby, and medicinal residues are retained.Get volatile oil,, get inclusion complex with 4 times of amount beta-schardinger dextrin-inclusions; Radix Astragali decocting extracts three times, adds 4 times in water at every turn, decocts 1 hour, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 50%, places 12 hours, and filtration gets ethanol liquid; Remaining Semen Persicae 36.12g, the Rhizoma Smilacis Glabrae of Semen Coicis 696.6g and recipe quantity, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, the decoction pieces of Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts three times, adds 4 times of amounts of water at every turn, decocted 1 hour, merge three times decocting liquid, and merge, filter with the Rhizoma Curcumae aqueous solution, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), take out, put coldly, add ethanol, make ethanol content reach 60%, placed 24 hours, and filtered, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and being condensed into thick paste, drying under reduced pressure (＜70 ℃) gets dry extract, pulverize, cross 60 mesh sieves, the fine powder of medicines such as the beta-cyclo dextrin included compound fine powder of adding Rhizoma Curcumae volatile oil and above-mentioned Cortex Cinnamomi adds an amount of excipient mixing, tabletting is made 1000, promptly.

Embodiment five

Granule

Take by weighing by recipe quantity: Radix Astragali 180.6g, Semen Persicae 387g, Rhizoma Curcumae 0g, Radix Et Rhizoma Rhei 64.5g, Rhizoma Smilacis Glabrae 387g, Semen Coicis 258g, Herba Leonuri 412.8g, Spica Prunellae 129g, Cortex Cinnamomi 38.7g, Radix Platycodonis 258g, Radix Cyathulae 258g.

Radix Astragali decocting extracts three times, adds 5 times in water at every turn, decocts 2 hours, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 70%, places 36 hours, and filtration gets ethanol liquid; The decoction pieces of Semen Persicae, Semen Coicis, Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, Radix Cyathulae, Rhizoma Curcumae, decocting extracts secondary, adds 8 times of amounts of water at every turn, decocted 1.5 hours, and merged decocting liquid twice, filter, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), take out, put coldly, add ethanol, make ethanol content reach 60%, placed 24 hours, and filtered, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and being condensed into thick paste, drying under reduced pressure (＜80 ℃) gets dry extract, pulverize, cross 50 mesh sieves, add an amount of dextrin, cyclamate is made granule, be drying to obtain.

Embodiment six

Take by weighing by recipe quantity: Radix Astragali 129g, Semen Persicae 387g, Rhizoma Curcumae 77.4g, Radix Et Rhizoma Rhei 129g, Rhizoma Smilacis Glabrae 387g, Semen Coicis 51.6g, Herba Leonuri 516g, Spica Prunellae 25.8g, Cortex Cinnamomi 103.2g, Radix Platycodonis 258g, Rhizoma Menispermi 258g, Radix Cyathulae 258g.

Radix Astragali decocting extracts three times, adds 7 times in water at every turn, decocts 2.5 hours, merges three times decocting liquid, and grass one wood filters, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, make ethanol content reach 55%, placed 18 hours, filter, get ethanol liquid; The decoction pieces of Semen Persicae, Semen Coicis, Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, Radix Cyathulae, Rhizoma Curcumae, decocting extracts four times, adds 4 times of amounts of water at every turn, decocted 1 hour, and merged decocting liquid twice, filter, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), take out, put coldly, add ethanol, make ethanol content reach 60%, placed 24 hours, and filtered, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and being condensed into thick paste, drying under reduced pressure (＜70 ℃) gets dry extract, pulverize, cross 30 mesh sieves, add an amount of dextrin, cyclamate is made granule, be drying to obtain.

Embodiment seven

The preparation of pill

Take by weighing Radix Astragali 460g, Semen Persicae 100g, Rhizoma Curcumae 130g, Radix Et Rhizoma Rhei 50g, Rhizoma Smilacis Glabrae 130g, Semen Coicis 510g, Herba Leonuri 220g, Spica Prunellae 380g, Cortex Cinnamomi 180g, Radix Platycodonis 160g, Rhizoma Menispermi 130g, Radix Cyathulae 130g by recipe quantity.

Get Cortex Cinnamomi, Radix Et Rhizoma Rhei and Semen Coicis 180g, Semen Persicae 15g, mixed powder is broken into fine powder; The Rhizoma Curcumae decoction pieces extracted volatile oil 7 hours with steam distillation, and the aqueous solution packaging container is standby, and medicinal residues are retained.Get volatile oil,, get inclusion complex with 8 times of amount beta-schardinger dextrin-inclusions; Radix Astragali decocting extracts three times, adds 9 times in water at every turn, decocts 3 hours, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 45%, places 20 hours, and filtration gets ethanol liquid; Remaining Semen Persicae 85g, Semen Coicis 330g adds the recipe quantity Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, the decoction pieces of Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts secondary, adds 8 times of amounts of water at every turn, decocted 1.5 hours, merge decocting liquid twice, and merge, filter with the Rhizoma Curcumae aqueous solution, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), take out, put coldly, add ethanol, make ethanol content reach 60%, placed 24 hours, and filtered, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and being condensed into thick paste, drying under reduced pressure (＜80 ℃) gets dry extract, pulverize, cross 80 mesh sieves, the fine powder of medicines such as the beta-cyclo dextrin included compound fine powder of adding Rhizoma Curcumae volatile oil and above-mentioned Cortex Cinnamomi is with an amount of dextrin mixing, with the general ball of ethanol, drying, promptly.

Embodiment eight

Take by weighing Radix Astragali 480g, Semen Persicae 120g, Rhizoma Curcumae 130g, Radix Et Rhizoma Rhei 50g, Rhizoma Smilacis Glabrae 140g, Semen Coicis 520g, Herba Leonuri 230g, Spica Prunellae 390g, Cortex Cinnamomi 190g, Radix Platycodonis 180g, Rhizoma Menispermi 150g by recipe quantity.

Get Cortex Cinnamomi, Radix Et Rhizoma Rhei and Semen Coicis 180g, Semen Persicae 15g, mixed powder is broken into fine powder; The Rhizoma Curcumae decoction pieces extracted volatile oil 9 hours with steam distillation, and the aqueous solution packaging container is standby, and medicinal residues are retained.Get volatile oil,, get inclusion complex with 3 times of amount beta-schardinger dextrin-inclusions; Radix Astragali decocting extracts three times, adds 8 times in water at every turn, decocts 2 hours, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 40%, places 24 hours, and filtration gets ethanol liquid; Remaining Semen Persicae 105g, Semen Coicis 340g adds the recipe quantity Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, the decoction pieces of Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts secondary, adds 8 times of amounts of water at every turn, decocted 1.5 hours, merge decocting liquid twice, and merge, filter with the Rhizoma Curcumae aqueous solution, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), take out, put coldly, add ethanol, make ethanol content reach 60%, placed 24 hours, and filtered, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and being condensed into thick paste, drying under reduced pressure (＜70 ℃) gets dry extract, pulverize, cross 40 mesh sieves, the fine powder of medicines such as the beta-cyclo dextrin included compound fine powder of adding Rhizoma Curcumae volatile oil and above-mentioned Cortex Cinnamomi is with an amount of dextrin mixing, with the general ball of ethanol, drying, promptly.

Embodiment nine

The preparation of powder

Take by weighing by recipe quantity: Radix Astragali 180.6g, Semen Persicae 387g, Rhizoma Curcumae 460.4g, Radix Et Rhizoma Rhei 77.4g, Rhizoma Smilacis Glabrae 309.6g, Semen Coicis 258g, Herba Leonuri 387g, Spica Prunellae 258g, Cortex Cinnamomi 77.4g, Radix Platycodonis 180.6g, Rhizoma Menispermi 51.6g, Radix Cyathulae 464.4g.

Get Cortex Cinnamomi, Radix Et Rhizoma Rhei and Semen Coicis 103.2g, Semen Persicae 81.47g, mixed powder is broken into fine powder; The Rhizoma Curcumae decoction pieces extracted volatile oil 7.5 hours with steam distillation, and the aqueous solution packaging container is standby, and medicinal residues are retained.Get volatile oil,, get inclusion complex with 10 times of amount beta-schardinger dextrin-inclusions; Radix Astragali decocting extracts three times, adds 8 times in water at every turn, decocts 1.5 hours, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 60%, places 24 hours, and filtration gets ethanol liquid; Remaining Semen Persicae, Semen Coicis adds Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, the decoction pieces of Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts secondary, adds 8 times of amounts of water at every turn, decocted 1.5 hours, merge decocting liquid twice, and merge, filter with the Rhizoma Curcumae aqueous solution, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), take out, put coldly, add ethanol, make ethanol content reach 60%, placed 24 hours, and filtered, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and being condensed into thick paste, drying under reduced pressure (＜70 ℃) gets dry extract, pulverize, cross 80 mesh sieves, the fine powder mixing of medicines such as the beta-cyclo dextrin included compound fine powder of adding Rhizoma Curcumae volatile oil and above-mentioned Cortex Cinnamomi is with ethanol system granule, dry packing, promptly.

Embodiment ten

Syrup

Take by weighing by recipe quantity: Radix Astragali 280g, Semen Persicae 200g, Rhizoma Curcumae 190g, Radix Et Rhizoma Rhei 10g, Rhizoma Smilacis Glabrae 260g, Semen Coicis 380g, Herba Leonuri 310g, Spica Prunellae 290g, Cortex Cinnamomi 130g, Radix Platycodonis 175g, Rhizoma Menispermi 175g, Radix Cyathulae 180g.

Radix Astragali decocting extracts three times, adds 8 times in water at every turn, decocts 1.5 hours, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 60%, places 24 hours, and filtration gets ethanol liquid; The decoction pieces of Semen Persicae, Semen Coicis, Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, Radix Cyathulae, Rhizoma Curcumae, decocting extracts secondary, adds 8 times of amounts of water at every turn, decocted 1.5 hours, and merged decocting liquid twice, filter, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), take out, put coldly, add ethanol, make ethanol content reach 60%, placed 24 hours, and filtered, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, reclaim ethanol, and be condensed into thick paste, add sucrose, refined honey is an amount of, mixing, adding preservative agent is an amount of, add water to 2500ml, filter, fill promptly.

Embodiment 11

Oral liquid:

Take by weighing by recipe quantity: Radix Astragali 310g, Semen Persicae 170g, Rhizoma Curcumae 190g, Radix Et Rhizoma Rhei 25g, Rhizoma Smilacis Glabrae 245g, Semen Coicis 390g, Herba Leonuri 300g, Spica Prunellae 280g, Cortex Cinnamomi 140g, Radix Platycodonis 200g, Rhizoma Menispermi 170g, Radix Cyathulae 160g.

Radix Astragali decocting extracts three times, adds 8 times in water at every turn, decocts 1.5 hours, merges three times decocting liquid, filters, and being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts coldly, adds ethanol, makes ethanol content reach 60%, places 24 hours, and filtration gets ethanol liquid; The decoction pieces of Semen Persicae, Semen Coicis, Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, Radix Cyathulae, Rhizoma Curcumae, decocting extracts secondary, adds 8 times of amounts of water at every turn, decocted 1.5 hours, and merged decocting liquid twice, filter, being concentrated into relative density is 1.05-1.35 (70 ℃ of surveys), takes out, and puts cold, add ethanol, make ethanol content reach 60%, placed 24 hours, filter, the ethanol liquid of the filtrate and the above-mentioned Radix Astragali merges, and reclaims ethanol, and is condensed into thick paste, add water to 2500ml, leave standstill, filter, it is an amount of to add correctives, regulate PH, leave standstill, filter, fill promptly.

Experimental example one

The logical capsule II clinical trial phase final report of closing of yellow cowherb

With the Longbishu Jiaonang. be contrast estimate demixing zone group that HuangCurcuma Tong closes capsule for treating hyperplasia of prostate blood stasis due to qi deficiency, damp and hot retardance card effectiveness and safety at random, double blinding, parallel control, multiple center clinical study.

According to the 200-ZL047 of National Drug Administration certification, the yellow cowherb of Guang-amen Hospital, China Traditional Chinese Medicine Instl, pharmaceutical Co. Ltd of Zhejiang Kang Enbei group being declared July 10 10 days to 2002 November of calendar year 2001 by 5 tame hospitals of Chinese medicine III kind new medicine is logical to close capsule for treating hyperplasia of prostate blood stasis due to qi deficiency, damp and hot retardance card has carried out the II clinical trial phase, and final report is as follows:

One, test objective

Observe the effectiveness that HuangCurcuma Tong closes capsule for treating hyperplasia of prostate blood stasis due to qi deficiency, damp and hot retardance card, its main purpose: the evaluation test medication is to the curative effect of international prostate gland symptoms scoring of hyperplasia of prostate patient (I-PSS) and urine flow rate; Secondary objective: the evaluation test medication is to the curative effect of symptom to related symptoms such as the influence of quality of life and sign integration, prostate size (B ultrasonic), residual urine volume of urinating.Safety evaluatio.

Two, test method

(1) EXPERIMENTAL DESIGN type, principle and test procedure

1. EXPERIMENTAL DESIGN type: adopt parallel control, demixing zone group at random, the method for designing of double blinding dual analog, multiple center trial.Whole test will be finished by domestic 5 hospital national drug clinical research bases are collaborative by this programme.

2. EXPERIMENTAL DESIGN principle

(1) case load: press II clinical trial phase contrast in 1: 1 principle, consider to be no more than 20% the rate that withdraws from, total routine number is defined as 120 pairs of totally 240 examples.Each test center is distributed 48 examples, and test group equates with matched group example number, respectively is 24 examples.

(2) random packet method: adopt center layering, district's group method of randomization.Produce the random arrangement that 240 routine experimenters accept to handle (investigational agent and contrast medicine) by the SAS statistical analysis system, promptly listing serial number is that 001～240 pairing treatment distributes (attached randoming scheme).The continuous programming code medicine that each central dispense 48 example is connected mutually.

Specify test center number at random: Nanjing Traditional Chinese Medicine Univ. affiliated hospital is 01, and Affiliated Hospital of Shanghai Univ. of Traditional Chinese Medicine is 02, and Hospital Affiliated To Chengdu Traditional Chinese Medicine Univ is 03, and The Affiliated Hospital to Jiangxi College of Traditional Chinese Medicine is 04, and Zhejiang College Of Traditional Chinese Medicine Affiliated Hospital is 05.

(3) contrast: the contrast medicine is selected Longbishu Jiaonang. (defending the accurate word Z39 of medicine) for use.Reason: Longbishu Jiaonang. is made up of Fructus Psoraleae, Herba Leonuri, Herba Lysimachiae, Spora Lygodii, succinum, Pseudobulbus Cremastrae Seu Pleiones etc.Function: the kidney warming activating QI, clearing heat and freeing strangury, blood circulation promoting and blood stasis dispelling, removing obstruction for relieving pain.Cure mainly: hyperplasia of prostate.This medicine function cures mainly and to test medication close, is the comparatively sure legal similar medicine of present domestic curative effect, meet generally acknowledge effectively, safety, comparable principle.

(2) case is selected

1. diagnostic criteria

Recommendation suggestion with reference to relevant prostatosis diagnosis of " new Chinese medicine clinical research guideline " the 3rd volume and International Coordinating Committee and treatment.

(1) Western medicine diagnose standard

1. male more than 50 years old.

2. dysuria history: urinate and hesitate, waste time and energy, the urine line is carefully unable, residual urine sense, nocturia frequency, even urinary incontinence.

3. anus is examined inspection: prostate two lateral lobes increase, and Rolandic fissure shoals or disappears.

4. ultrasound diagnosis: prostate volume increases, or luminous point is inhomogeneous, or bladder has residual urine.Weight of prostate＞20 grams.

5. uroflometry: urine amount 〉=200 milliliter, maximum urine flow＜15 milliliters/second, AFR＜10ml/ second.

4. and other each persons the 2. allly possess,, can be diagnosed as hyperplasia of prostate.

(2) Chinese medical discrimination standard (blood stasis due to qi deficiency, damp and hot retardance card)

Primary symptom:

Dysuria.

Inferior disease:

1. the urine meaning is anxious frequently, or swollen full, the distending pain of lower abdomen.

2. spiritual tired, anorexia is breathed hard.

3. light red tongue is purple or petechia, yellow, greasy and thin fur arranged.Thready and hesitant pulse or thin string or thin and delicate.

(3) symptom and sign quantitative criteria

Method according to international prostate gland symptoms scoring (I-PSS) and appraisal of life quality, the relevant symptom of urinating is divided into 0～5 six scoring section, and total scoring scope is 0～35, expresses with S 0～35, appraisal of life quality is divided 0～6 seven scoring section, expresses with L 0～6.

(4) severity extent grade scale

The first phase (irritation phase): bladder, urethra, perineum are slightly uncomfortable, frequent micturition, and slight dysuria mainly shows as the nocturia frequency, residual urine＜50ml.International prostate gland symptoms scoring (I-PSS)≤7 minute.

The second phase (residual urine phase): carrying out property dysuria, conscious exerting oneself when urinating, residual urine volume 50-150ml, acute urinary retention, urinary tract infection can take place in this phase.I-PSS scoring 8-19 branch.

The third phase (bladder loses the compensatory phase): residual urine volume＞150ml, bladder enlarges, and renal function begins impaired, the urinary retention with overflow incontinence symptom occurs.I-PSS scoring 20-35 branch.

2. include standard in

(1) meet prostatic hyperplasia 1,2 phases diagnostic criteria, dialectical standard person is demonstrate,proved in traditional Chinese medical science blood stasis due to qi deficiency, damp and hot retardance.

(2) male, the age is between 50～80 years old.

(3) do not used the Chinese and western drugs for the treatment of prostatic hyperplasia since the nearly week.

(4) informed consent, aspiration is tried.Obtain the Informed Consent Form process and should meet the 6CP regulation.

3. the experimenter withdraws from the condition of test

(1) anaphylaxis or serious adverse reaction person occur, judge according to the doctor stop clinical trial person, promptly end this case clinical trial.

(2) complication such as urinary tract infection, acute urinary retention occur, or two weeks of taking medicine continuously fail to respond to any medical treatment or sb.'s illness took a turn for the worse, judge according to the doctor stop clinical trial person, promptly end this case clinical trial.

(3) patient is unwilling to proceed clinical trial in the clinical trial process, to the requirement of physician proposition termination clinical trial, can end this case clinical trial.

(3) therapeutic scheme

1. test medication title and specification

The test medication: yellow cowherb is logical to close capsule, and pharmaceutical Co. Ltd of Kang Enbei group provides by bidding person Zhejiang.Specification: 0.4 gram/grain, 50/bottle, lot number 010305.

The contrast medicine: Longbishu Jiaonang., produce specification 0.3 gram/grain, 48/box, lot number 010308 by Shijiazhuang City Ke Di pharmaceutcal corporation, Ltd.

2. test medication random coded is blind with volume

Bidding person carries out random coded according to scheme adnexa " clinical trial randoming scheme " to the test medication.Test medication random coded is experimenter's unique identifier.Each coding medicine is joined an emergent mail, is used for urgent broken blind.Monitor and researcher must be in blind attitude from start to finish.Being numbered No. 000 of stage of preparation medicine placebo.

3. method of administration

The double blinding double dummy technique:

Test group: the logical capsule that closes of yellow cowherb, prescription is formed: compositions such as the Radix Astragali, Rhizoma Curcumae, Semen Persicae, Herba Leonuri, Semen Coicis, Cortex Cinnamomi.Longbishu Jiaonang. (placebo), oral, each 3,2 times on the one.

Matched group: Longbishu Jiaonang., prescription is formed: be made up of Fructus Psoraleae, Herba Leonuri, Herba Lysimachiae, Spora Lygodii, succinum, Pseudobulbus Cremastrae Seu Pleiones etc.Oral, each 4,3 times on the one.Yellow cowherb is logical to close capsule (placebo), oral, and each 3,2 times on the one.

Taking medicine continuously 42 days is 1 course of treatment, and further consultation in per 14 days once.Be 1 course of treatment observing time.After clinical trial finishes, by routine clinical method treatment.

The stage of preparation medicine: placebo, oral.Each 4,3 times on the one.Take treatment prostatic hyperplasia medicine person in the last week on-test, took the stage of preparation medicine earlier.

(4) curative effect and safety observation index

1. main curative effect index

International prostate gland symptoms scoring (I-PSS).Earlier to patient the get across content and the meaning of this scale, strictly then everyly carry out one by one by grade form is listed.

Uroflometry.Special-purpose inspection chamber, special-purpose uroflometry instrument, special messenger's operation.Drinking-water 400ml checked after 2 ~ 4 hours before detecting.Must guarantee that the urine amount reaches 200ml ~ 400ml.

2. secondary efficacy index

The symptom of urinating is to related symptoms and the signs such as influence of quality of life.

The prostate ultrasound diagnosis.

Residual urine volume is measured.

3. safety is observed

Adverse events.Blood, routine urinalysis, stool routine examination.Electrocardiogram, liver function (ALT), renal function (BUN, Scr).

(5) curative effect and safety assessment standard

1. comprehensive therapeutic effect evaluation criteria (with reference to " new Chinese medicine clinical research guideline " the 3rd volume)

Produce effects: 1. the I-PSS scoring≤7, L index≤1, or state of an illness total mark reduces more than 90%; 2. prostate volume dwindle 〉=20% or residual urine volume reduce more than 70%; 3. Qmax＞16ml/ second.More than possessing 2 gets final product.

Effectively: 1. I-PSS scoring≤13, and index L 4～6 is reduced to 2～3 before the treatment, or state of an illness total mark reduces more than 60%; 2. prostate volume dwindles below 10～20% or residual urine volume reduces more than 50%; 3. Qmax has increase.More than possessing 1 gets final product.

Invalid: as not reach effective standard.

2. safety evaluatio standard

1 grade: safety, there is not any untoward reaction.

2 grades: compare safety,, need not do any processing and can continue administration if any untoward reaction.

3 grades: safety issue is arranged, moderate untoward reaction is arranged, can continue administration after processing.

4 grades: because of test is ended in untoward reaction.

3. adverse events light and heavy degree criterion

Slightly: the experimenter can stand, and does not influence treatment, does not need special processing, and experimenter's rehabilitation is not had influence.

Moderate: the experimenter is difficult to stand, and needs withdrawal to end to test or do special handling, and experimenter's rehabilitation is had a direct impact.

Severe: jeopardize experimenter's life, cause death or disable, need withdrawal immediately or do emergent management.

(6) conclusion: 235 routine cases are finished in this test altogether, and wherein 118 examples are organized in treatment, matched group 117 examples.Result of the test shows:

1. two groups contrast the equal not statistically significant of difference between each parameters for observation on effect treatment front and back group.Show the logical curative effect index difference not statistically significant that closes capsule and contrast medicine LONGBISHU of the yellow cowherb of investigational agent.

2. reduction is worth 7.6 soil 4.61 before and after meeting the treatment of the main curative effect index IPSS of scheme collection test group, and matched group 7.9 ± 4.38 has clinical meaning; Lift-off value (median) is 3.0 before and after the treatment of terminal point urine flow rate test group, and matched group 2.8 has clinical meaning.

3. meet scheme collection test group obvious effective rate 14.9%, total effective rate 95.6%, matched group is respectively 8.5%, 96.2%; Complete analysis collection test group obvious effective rate 17%, total effective rate 97%, matched group is respectively 8.3%, 94.4%, the difference not statistically significant of two groups of curative effects.

Experimental example two

The logical capsule III clinical trial phase final report of closing of yellow cowherb

With the Longbishu Jiaonang. be contrast estimate demixing zone group that HuangCurcuma Tong closes capsule for treating benign prostate hyperplasia blood stasis due to qi deficiency, damp and hot retardance card effectiveness and safety at random, double blinding, parallel control, multiple center clinical study

According to the 2000-ZL047 of National Drug Administration certification, by Nanjing Traditional Chinese Medicine Univ. affiliated hospital, Longhua Hospital affiliated Shanghai University Of Chinese Traditional Medicine, The Affiliated Hospital to Jiangxi College of Traditional Chinese Medicine, Zhejiang College Of Traditional Chinese Medicine Affiliated Hospital, Affiliated Hospital of Hunan University of Traditional Chinese Medicine, attached the 3rd hospital of Zhejiang College Of Traditional Chinese Medicine, totally 5 tame hospitals in JIUYUE in 2003 24 days on 03 16th, 2005 to Guang-amen Hospital, China Traditional Chinese Medicine Instl, the logical capsule for treating benign prostate hyperplasia blood stasis due to qi deficiency of closing of the yellow cowherb of Chinese medicine three kind new medicines that Zhejiang pharmaceutical Co. Ltd of Kang Enbei group declares, damp and hot retardance card has carried out the III clinical trial phase, and interim report is as follows.

One, test objective

Main purpose:, estimate the clinical efficacy that HuangCurcuma Tong closes capsule for treating benign prostate hyperplasia blood stasis due to qi deficiency, damp and hot retardance card by observing the situation of change that international prostate gland symptoms is marked (I-PSS), Qmax is measured before and after the treatment; Secondary objective: observe the variation that the symptom of urinating is measured related symptoms such as the influence of quality of life and sign, prostate ultrasound diagnosis, residual urine volume simultaneously.

By the adverse events of observing the heart, liver, renal function and may occurring, its safety is made an appraisal.

Two, test method

(1) EXPERIMENTAL DESIGN type, principle

1. EXPERIMENTAL DESIGN type: parallel at random group control design.Non-bad effect check.

2. EXPERIMENTAL DESIGN principle

(1) case load: according to II clinical trial phase result, matched group Qmax treatment back improvement 〉=3ml/ second is 50%, by non-bad effect clinical trial estimation of sample size formula, under the significance level of α=0.05, setting non-bad effect dividing value δ is 0.15, need test about 138 examples for every group, then can reach the power of a test more than 80%.Be not less than 300 routine numbers according to " medicine registration management way " III clinical trial phase test group, so adopt 2: 1 contrast principles, consider that II clinical trial phase expulsion rate is about 10%, so total routine number of this test is defined as 486 examples, test group 324 examples wherein, matched group 162 examples.

(2) random packet: adopt center layering, district's group method of randomization.Produce the random arrangement that 486 routine experimenters accept to handle (investigational agent and contrast medicine) by the SAS statistical analysis system, promptly listing serial number is that 001～486 pairing treatment distributes (attached randoming scheme).The continuous programming code medicine that each central dispense 81 example is connected mutually.This test is worked in coordination with by the national drug clinical research base of 6 hospitals and is finished this test.Specify test center number at random: Nanjing Traditional Chinese Medicine Univ. affiliated hospital is 06, Longhua Hospital affiliated Shanghai University Of Chinese Traditional Medicine is 01, The Affiliated Hospital to Jiangxi College of Traditional Chinese Medicine is 04, Zhejiang College Of Traditional Chinese Medicine Affiliated Hospital is 05, Affiliated Hospital of Hunan University of Traditional Chinese Medicine is 02, and attached the 3rd hospital of Zhejiang College Of Traditional Chinese Medicine is 03 (SDA certification sequence arrangement is pressed at each center).

(3) contrast: the contrast medicine is selected Longbishu Jiaonang. (defending the accurate word Z39 of medicine) for use.Reason: Longbishu Jiaonang. is made up of Fructus Psoraleae, Herba Leonuri, Herba Lysimachiae, Spora Lygodii, succinum, Pseudobulbus Cremastrae Seu Pleiones etc.Function: the kidney warming activating QI, clearing heat and freeing strangury, blood circulation promoting and blood stasis dispelling, removing obstruction for relieving pain.Cure mainly: benign prostate hyperplasia.This medicine function cures mainly close with trial drug, is the comparatively sure similar medicine of present domestic curative effect, meets to generally acknowledge effectively similar comparable principle.

(2) case is selected

1. diagnostic criteria

(1) benign prostate hyperplasia Western medicine diagnose standard (formulating) with reference to " the recommendation suggestion of relevant prostatosis patient diagnosis of International Coordinating Committee and treatment " 4

1. male more than 50 years old.

2. dysuria history: urinate and hesitate, waste time and energy, the urine line is carefully unable, residual urine sense, nocturia frequency, even urinary incontinence.

3. anus is examined inspection: prostate two lateral lobes increase, and Rolandic fissure shoals or disappears.

4. ultrasound diagnosis: prostate volume increases, or luminous point is inhomogeneous, or bladder has residual urine.Prostate volume＞24ml.

5. uroflometry: urine amount＞150 milliliter, Qmax＜15ml/ second, AFR＜10ml/ second.

The 2. allly possess, 4., 5. and/or other each persons, can be diagnosed as benign prostate hyperplasia.

(2) Chinese medical discrimination standard

Primary symptom: dysuria.

Inferior disease: 1. the urine meaning is anxious frequently, or swollen full, the distending pain of lower abdomen.2. spiritual tired, anorexia is breathed hard.3. light red tongue is purple or petechia, yellow, greasy and thin fur arranged.Thready and hesitant pulse or thin string or thin and delicate.

(3) prostatic hyperplasia standard by stages

The first phase (irritation phase): bladder, urethra, perineum are slightly uncomfortable, frequent micturition, and slight dysuria mainly shows as the nocturia frequency, residual urine＜50ml.International prostate gland symptoms scoring (I-PSS))≤7 minutes.

The second phase (residual urine phase): carrying out property dysuria, conscious exerting oneself when urinating, residual urine volume 50-150ml, acute urinary retention, urinary tract infection can take place in this phase.I-PSS scoring 8-19 branch.

The third phase (bladder loses the compensatory phase): residual urine volume＞150ml, bladder enlarges, and renal function begins impaired, the urinary retention with overflow incontinence symptom occurs.I-PSS scoring 20-35 branch.

(4) disease weight grade scale (formulating) with reference to " the recommendation suggestion of relevant prostatosis patient diagnosis of International Coordinating Committee and treatment " 3

Method according to international prostate gland symptoms scoring (I-PSS) and appraisal of life quality, the relevant symptom of urinating is divided into 0～5 six scoring section, and total scoring scope is 0～35, expresses with S 0～35, appraisal of life quality is divided 0～6 seven scoring section, expresses with L 0～6.

2. include standard in

(1) meet benign prostate hyperplasia 1,2 phases diagnostic criteria, dialectical standard person is demonstrate,proved in traditional Chinese medical science blood stasis due to qi deficiency, damp and hot retardance.

(2) male, the age is between 50～80 years old.

(3) do not used the Chinese and western drugs for the treatment of prostatic hyperplasia since the nearly week.

(4) informed consent, aspiration is tried.Obtain the Informed Consent Form process and should meet the GCP regulation.

3. the experimenter withdraws from the condition of test

(1) anaphylaxis or serious adverse events person occur, judge according to the doctor stop clinical trial person, promptly end this case clinical trial.

(2) occur in the course of disease that sb.'s illness took a turn for the worse, judge according to the doctor stop clinical trial person, promptly end this case clinical trial.Making invalid case handles.

(3) patient is unwilling to proceed clinical trial in the clinical trial process, proposes to withdraw from the requirement of clinical trial to physician, can withdraw from this case clinical trial.

(3) therapeutic scheme

1. test medication title and specification

The test medication: yellow cowherb is logical to close capsule, is provided by bidding person.Prescription is formed: the Radix Astragali, Semen Persicae, Rhizoma Curcumae, Radix Et Rhizoma Rhei, Rhizoma Smilacis Glabrae, Semen Coicis, Herba Leonuri, Spica Prunellae, Cortex Cinnamomi, Rhizoma Menispermi, Radix Platycodonis, Radix Cyathulae.Specification: 0.4 gram/grain, 50/bottle, lot number * * * * *.

The contrast medicine: Longbishu Jiaonang., to produce by Shijiazhuang City Ke Di pharmaceutcal corporation, Ltd, prescription is formed: Fructus Psoraleae, Herba Leonuri, Herba Lysimachiae, Spora Lygodii, succinum, Pseudobulbus Cremastrae Seu Pleiones etc.Specification 0.3 gram/grain, 48/box, lot number * * * * *.

2. method of administration

Test group: yellow cowherb is logical to close capsule, oral, and each 4,3 times on the one.Longbishu Jiaonang. (placebo), oral, each 3,2 times on the one.

The contrast medicine: yellow cowherb is logical to close capsule (placebo), oral, and each 4,3 times on the one.Longbishu Jiaonang., oral, each 3,2 times on the one.

Taking medicine continuously 42 days is 1 course of treatment, and further consultation in per 14 days once.Be 1 course of treatment observing time.

(4) curative effect and safety observation index

1. biological indicator

Demographic characteristics: sex, age, height, body weight

Vital sign: body temperature, resting heart rate, the blood pressure (systolic pressure, diastolic pressure) after breathing, having a rest 10 minutes

2. diagnosis index

Symptom and sign, anus are examined inspection, the course of disease, severity extent, body of the tongue, tongue fur, pulse condition.

The physico-chemical examination diagnosis index: ultrasound diagnosis, uroflometry, blood PSA detect (in case of necessity).

3. curative effect index

(1) main curative effect index

International prostate gland symptoms scoring (I-PSS).

Qmax is measured.

(2) secondary efficacy index

The symptom of urinating is to related symptoms and the signs such as influence of quality of life.

The physico-chemical examination index: ultrasound diagnosis prostate size is also calculated weight of prostate in view of the above, and residual urine volume is measured.

(3) comprehensive therapeutic effect.

4. safety is observed

Blood, routine urinalysis, stool routine examination.

Electrocardiogram, liver function (ALT), renal function (BUN, Scr).

Adverse events.

Safety evaluatio.

5. test evaluation index

Whether come off.

Compliance.

(5) curative effect and safety assessment standard

1. efficacy assessment standard

(1) effective: as treat back Qmax improvement 〉=3ml/ second, or the I-PSS scoring to reduce by 30%.

(2) invalid: as not reach effective standard.

2. safety evaluatio standard

1 grade: safety, there is not any untoward reaction.

2 grades: compare safety,, need not do any processing and can continue administration if any untoward reaction.

3 grades: safety issue is arranged, moderate untoward reaction is arranged, can continue administration after processing.

4 grades: because of test is ended in untoward reaction.

3. adverse events light and heavy degree criterion

Slightly: the experimenter can stand, and does not influence treatment, does not need special processing, and experimenter's rehabilitation is not had influence.

Moderate: the experimenter is difficult to stand, and needs withdrawal to end to test or do special handling, and experimenter's rehabilitation is had a direct impact.

Severe: jeopardize experimenter's life, cause death or disable, need withdrawal immediately or do emergent management.

(6) conclusion: case 485 examples are finished in this test altogether, test group 323 examples wherein, matched group 162 examples.Result of the test shows:

It is-3.41 that the non-pessimum check that treatment group and matched group terminal point IPSS effective percentage meet scheme collection test group and matched group comparison has statistical significance, the 95%CL of non-pessimum.It is-3.49 that the non-pessimum check of complete analysis collection test group and matched group comparison has statistical significance, the 95%CL of non-pessimum.

It is-4.18 that the non-pessimum check that two groups of terminal point Qmax effective percentage meet scheme collection test group and matched group comparison has statistical significance, the 95%CL of non-pessimum.It is-4.40 that the non-pessimum check of complete analysis collection test group and matched group comparison has statistical significance, the 95%CL of non-pessimum.

Comprehensive therapeutic effect meets the difference no statistical significance of two groups of scheme collection.The non-pessimum check of test group and matched group comparison has statistical significance.The 95%CL of non-pessimum is-5.98.The difference no statistical significance that the complete analysis collection is two groups.The non-pessimum check of test group and matched group comparison has statistical significance.The 95%CL of non-pessimum is-6.30.

Constantly put into practice demonstration and near, modern summary raising of curing house by ancient Chinese medicine doctor, the difficulty in urination (hyperplasia of prostate) is though Chinese materia medica thinks that etiology and pathogenesis is more, but Most patients shows as qi depression to blood stasis, damp and hot retardance clinically, so with blood circulation promoting and blood stasis dispelling, eliminating damp-heat is the main rule of treatment.Modern Chinese medicine and modern medicine index observing are adopted in this research, and with phenoxybenzamine, QIANLIEKANG etc. serve as the contrast medicine treat 237 examples, total effective rate reaches patient's prostate volume of 60.5%, 36.2% and dwindles, and not only can alleviate the dysuria symptom, reduce the nocturia number of times, and can improve urine flow rate parameter, and reduce residual urine volume, in similar medicine, have superiority, and do not have obvious toxic-side effects, safe and reliable.

Claims (11)

1. medicine for the treatment of benign prostate hyperplasia, it is characterized in that: it is to be monarch drug with the Radix Astragali, Semen Persicae, Rhizoma Curcumae, Radix Et Rhizoma Rhei, Rhizoma Smilacis Glabrae, Semen Coicis, Herba Leonuri, Spica Prunellae are ministerial drug, Cortex Cinnamomi, Radix Platycodonis, Rhizoma Menispermi are adjuvant drug, and Radix Cyathulae is that messenger drug is equipped with the medically acceptable all kinds of preparations that pharmaceutic adjuvant is formed.

2. the medicine of treatment benign prostate hyperplasia according to claim 1 is characterized in that the weight proportion of each active ingredient is (in crude drug):

Radix Astragali 5%-20% Semen Persicae 2%-15% Rhizoma Curcumae 0%-10%

Radix Et Rhizoma Rhei 0%-5% Rhizoma Smilacis Glabrae 1%-15% Semen Coicis 2%-30%

Herba Leonuri 2%-20% Spica Prunellae 1%-20% Cortex Cinnamomi 0%-10%

Radix Platycodonis 0%-10% Rhizoma Menispermi 0%-10%.Radix Cyathulae 0%-10%.

3. the medicine of treatment benign prostate hyperplasia according to claim 1 is characterized in that the weight proportion of each active ingredient is (in crude drug):

Radix Astragali 7%-18% Semen Persicae 2%-15% Rhizoma Curcumae 3%-10%

Radix Et Rhizoma Rhei 0%-3% Rhizoma Smilacis Glabrae 5%-15% Semen Coicis 10%-30%

Herba Leonuri 5%-20% Spica Prunellae 5%-20% Cortex Cinnamomi 3%-10%

Radix Platycodonis 3%-10% Rhizoma Menispermi 3%-10%.Radix Cyathulae 3%-10%.

4. the medicine of treatment benign prostate hyperplasia according to claim 1 is characterized in that the weight proportion of each active ingredient is (in crude drug):

The Radix Astragali 11.63% Semen Persicae 6.97% Rhizoma Curcumae 6.97%

Radix Et Rhizoma Rhei 0.78% Rhizoma Smilacis Glabrae 9.30% Semen Coicis 15.50%

Herba Leonuri 11.63% Spica Prunellae 11.63% Cortex Cinnamomi 4.65%

Radix Platycodonis 6.97% Rhizoma Menispermi 6.97%.Radix Cyathulae 6.97%.

5. according to claim 1 or 2 or the medicine of 3 or 4 described treatment benign prostate hyperplasias, it is characterized in that described medically acceptable all kinds of preparations comprise capsule, tablet, granule, pill, powder, syrup, oral liquid.

6. according to claim 1 or 2 or the preparation method of the medicine of 3 or 4 described treatment benign prostate hyperplasias, it is characterized in that it comprises following process steps:

(1) takes by weighing raw material by the said ratio amount;

(2) get Cortex Cinnamomi, Radix Et Rhizoma Rhei and 10%-50% Semen Coicis, the 5%-30% Semen Persicae of formula ratio, mixed powder is broken into fine powder;

(3) Rhizoma Curcumae decoction pieces water vapour distillation volatile oil, the aqueous solution packaging container is standby, and medicinal residues are retained, and get volatile oil, use the beta-schardinger dextrin-inclusion, get inclusion complex;

(4) Radix Astragali decocting extracts secondary or more than the secondary, collecting decoction filters, and is concentrated into thick paste, puts coldly, adds ethanol, leaves standstill, filter, ethanol liquid;

(5) Yu Xia Semen Persicae, Semen Coicis add the decoction pieces of Rhizoma Smilacis Glabrae, Rhizoma Menispermi, Spica Prunellae, Herba Leonuri, Radix Platycodonis, Radix Cyathulae, the medicinal residues of Rhizoma Curcumae, decocting extracts secondary or more than the secondary, collecting decoction, be concentrated into thick paste, add ethanol, leave standstill, filter, the ethanol liquid of the filtrate and the aforementioned Radix Astragali merges, reclaim ethanol, and being condensed into thick paste, drying under reduced pressure gets dry extract, pulverize, sieve, the fine powder mixing of medicines such as the beta-cyclo dextrin included compound fine powder of adding Rhizoma Curcumae volatile oil and aforesaid Cortex Cinnamomi is equipped with pharmaceutic adjuvant and makes medically acceptable all kinds of preparations.

7. the process for preparing medicine of treatment benign prostate hyperplasia according to claim 6 is characterized in that: the described water vapour distillation time of step (3) is 6-10 hour.

8. the preparation method of the medicine of treatment benign prostate hyperplasia according to claim 6 is characterized in that: the 3-10 that the described beta-schardinger dextrin-consumption of step (3) is a volatile oil doubly measures.

9. the preparation method of the medicine of treatment benign prostate hyperplasia according to claim 6, it is characterized in that: the described Radix Astragali decocting of step (4) adds water 4-10 doubly at every turn, decocted 1-3 hour, thick paste density is 1.05-1.35 (70 ℃ of surveys), ethanol content reaches 40%-80% when adding ethanol precipitation, and be 6-48 hour standing time.

10. the preparation method of the medicine of treatment benign prostate hyperplasia according to claim 6, it is characterized in that: the water yield that decocting extracts in the step (5) is that each 4-10 doubly measures, decocting time is 1-3 hour, thick paste density is 1.05-1.35 (70 ℃ of surveys), ethanol content reaches 40%-80% when adding ethanol precipitation, and be 6-48 hour standing time.

11. the preparation method of the medicine of treatment benign prostate hyperplasia according to claim 6 is characterized in that: drying under reduced pressure is at＜80 ℃ in the step (5), and sieving is the 30-80 order.