CN1943701A - A kind of medicine for treatment of non-gonococcal urethritis(NGU) and its preparation method - Google Patents
A kind of medicine for treatment of non-gonococcal urethritis(NGU) and its preparation method Download PDFInfo
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Abstract
This invention relates to the field of the Chinese traditional medical technology. It reveals a kind of medicine for treatment of non-gonococcal urethritis(NGU) and its preparation method. The medicine takes abstracts distilled from the following 6 Chinese medical ingredients as the active components: common fibraurea stem, jingangteng, dandelion herb, Chinese corktree bark, Indian quassiawood twig and leaf, snowbelleaf tickclover herb, use the above 6 ingredients to prepared the medicine by adding right weight of adjuvant material, then press them into tablets and have the tablets coated wit th thin film so to form film coated tables. Results of pharmacological researches show that the medicine of this invention has actions of excellent resisting germs, infections, benefit urination, relieving pain, expelling heat, and it can effectively reduce the infection of the urinating rout of rat. Acute and normal toxin studies show that the medicine is safe when used according the given clinical dosage.
Description
Technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, particularly relate to a kind of medicine for the treatment of nongonococcal urethritis and preparation method thereof.
Background technology
Nongonococcal urethritis is a kind of common sexually transmitted disease (STD).
Nongonococcal urethritis is a kind of common, multiple urinary system illness, it is a kind of sexually transmitted disease (STD) that sickness rate is only second to gonorrhea and condyloma acuminatum, also has the trend that constantly rises at present, China in 1998 has reported to suffer from about 120,000 examples of nongonococcal urethritis patient, and along with China recurrent population's the growth and the opening of attitude towards sex, the nongonococcal urethritis patient is quick growing trend. the new drug of research treatment nongonococcal urethritis has certain realistic meaning.
Western medicine thinks that this disease is mainly caused by chlamydia and mycoplasma, infects by sexual intercourse, invades the urogenital organ.The male mainly shows as the scratchy and pain of urinating of urethra clinically, and minority has frequent micturition, a small amount of mucus secretions is arranged or only have the crust film to seal from the beginning of urethral orifice, often merges epididymitis, prostatitis etc.The women is many to be that the center is diffused into other positions with the cervix uteri, shows as the urogenical infection symptom.Mucus cervicitis person performance has leucorrhoea grow in quantity, edema of cervix or erosion; Urethritis person shows as urethra scorching hot or frequent micturition, checks urethral orifice hyperemia, little red or normal, and the extruding urethra has secretions to overflow, and many patients do not have any symptom.Generally select the medicine to mycoplasma and chlamydia cosensitize in the treatment for use, as tetracycline, doxycycline, Roxithromycin, ofloxacin etc., but all class medicines all have stronger toxic action, are easy to generate drug resistance, and curative effect and prognosis are not satisfactory.
Nongonococcal urethritis is according to its clinical manifestation and genius morbi, disease categories such as ownership motherland's medical science " stranguria ", " stranguria with turbid discharge ", " it is turbid to drown ", " nebulousurine ", " women's leukorrhagia ", theory of Chinese medical science thinks, it takes place how unclean or infect foul heresy by chamber, gone into by excessive key or vaginal orifice, the retardance part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels, wet and accumulate heat-transformation, damp-heat accumulation bladder, with the passing of time heat-transformation yin-damaging and Qi consuming, functioning of bladder is unfavorable, satisfies and sends out stranguria.The most common with syndrome of dampness-heat in lower jiao clinically.
The name of " stranguria ", head sees " interior warp ".The Han dynasty is opened machine and in " Medical Treasures of the Golden Chamber quench one's thirst normal urination gonorrhea arteries and veins card and control " symptom of primary disease has been done record, says: " pourings be disease, obstructed urine as dripping, contraction in the lower abdomen, dragging pain in the navel ", and think that its pathogenesis is " heat in lower-JIAO ".Ming Dynasty Lee stile " Elementary Medicine pouring " further describes: " drench difficulty and pain in micturition, desire to go or not, do not go to come again, drip constantly." then says among the Ming Dynasty Zhang Jiebin " Jing Yue's complete work assorted card unconcerned stranguria with turbid discharge ": " pourings for sick, whether the puckery sound of rain pattering bitterly of urinating desired to go or not, it is also that desire is ended more than person ".
Zhang Jingyue thinks that stranguria is relevant with " long-pending intrinsic heat poison ", say: " sick at the beginning of the pouring; then invariably by popular drama, as not have to hold and distinguish ", to its treatment, advocated executing of " all hot persons being suitable clear; puckery person is suitable sharp, the suitable ascending of the person of sinking, empty person should mend; the person should warming and recuperating the gate of life admittedly for yang-energy " and controlled principle with card, by after physicians from a family for generations family deferred to when demonstrate,proving diagnosis and treatment facing.Have recognized that in " all source of disease times " that stranguria has the situation of recurrence to exist.
" danxi's experiential therapy pouring " said: " pouring person all belongs to heat.Analgesic diuresis, SHANZHIZI and so on ", indicated the method for the clearing away heat-damp and promoting diuresis of controlling pouring, by diuresis heat is gone with wet." Jing Yue's complete work assorted card unconcerned stranguria with turbid discharge " said: " opinion is controlled: heat is held bladder, dark coloured urine heat even or bitterly or puckery person, should specially remove its fire ... ".
Stranguria is the disease of clinical common pilosity, and human health is had bigger influence, and not only short term effect is good to the treatment of this card for Chinese medicine, and side effect is little, and late result is also comparatively desirable.From western modern medicine pharmacological research angle, killing pathogen, suppress the adhesion of antibacterial, 3 of human body immunity improving functions are prevented and treated in the important step of urinary tract infection, Chinese medicine has remarkable advantages aspect latter two, but also there are some problem demanding prompt solutions: more as the clinical efficacy discussion, and experimentation is less; Aspect dosage form, use decoction in addition, other dosage form is less more, is unfavorable for the utilization and the popularization of active drug.
Summary of the invention
A kind of medicine for the treatment of nongonococcal urethritis of the present invention is under instruction of Chinese Medicine theory, and in conjunction with development person's clinical experience, and with reference to the modern pharmacological research achievement and prescription, technology, drug effect, toxicologic study trial-production through for many years form.
The purpose of this invention is to provide a kind of medicine for the treatment of nongonococcal urethritis.
Another object of the present invention provides a kind of preparation method for the treatment of the medicine of nongonococcal urethritis of suitability for industrialized production.
The present invention is achieved by the following technical solutions.
The invention provides a kind of medicine for the treatment of nongonococcal urethritis, it is characterized in that it is that Chinese crude drug by following prescription is prepared from through extract 2-2.2 weight portion and the 1 weight portion pharmaceutic adjuvant that extraction obtains.
Its Chinese crude drug prescription is:
Caulis Fibraureae 833g Rhizoma Smilacis Bockii 833g Herba Taraxaci 833g
Cortex Phellodendri 416g Ramulus Et Folium Picrasmae 416g Herba Desmodii Styracifolii 833g
Make 1000, its dosage form is special-shaped Film coated tablets.
Wherein pharmaceutic adjuvant comprises disintegrating agent carboxymethyl base Starch Sodium, binder starch, lubricant Pulvis Talci, wetting agent ethanol water, coating materials Opadry; Carboxymethyl starch sodium weight portion wherein: the starch weight portion is 3: 2.
The pharmaceutic adjuvant consumption is in extract obtained weight portion:
The total amount 0.4 Pulvis Talci 0.007-0.008 of starch and carboxymethyl starch sodium
A kind of preparation method for the treatment of the medicine of nongonococcal urethritis is characterized in that comprising the steps:
(1) gets Rhizoma Smilacis Bockii, Herba Taraxaci, Ramulus Et Folium Picrasmae, Herba Desmodii Styracifolii by recipe quantity and add 16 times of amount 70% alcohol reflux twice, 2 hours for the first time; 1 hour for the second time.Filter, merging filtrate, decompression filtrate recycling ethanol also is concentrated into the thick paste shape, vacuum drying, temperature is 60 ℃ when dry, pulverizes, and crosses 80 mesh sieves, gets the ethanol extract of Rhizoma Smilacis Bockii, Herba Taraxaci, Ramulus Et Folium Picrasmae, Herba Desmodii Styracifolii;
(2) by prescription measure Caulis Fibraureae, Cortex Phellodendri powder is broken into coarse powder, adds 0.2% sulfuric acid solution and soaks, amount of liquid just covers the medical material face, 48 hours for the first time, 12 hours for the second time, 12 hours for the third time.Filter, filtrate is transferred pH to 9 with 20% sodium hydroxide solution, adds 8% sodium chloride, stir, and standing over night, centrifugal, the precipitation oven dry is pulverized, and crosses 80 mesh sieves, promptly gets Caulis Fibraureae, Cortex Phellodendri extract;
(3) above two kinds of extracts are merged, mix, add starch, carboxymethyl starch sodium, stir evenly, adding concentration is 50% alcoholic solution moistening, with the granulation of 16 mesh sieves, granulate, add Pulvis Talci, mixing, tabletting is with 14% Opadry (model is 65G62830) solution coating, promptly.
Being monarch drug with the Caulis Fibraureae heat-clearing and toxic substances removing in the side, is minister with the Rhizoma Smilacis Bockii of expelling wind and removing dampness, detoxifcation dissipating blood stasis, and assistant makes with Herba Desmodii Styracifolii antibacterial and detoxicating, dehumidifying, inducing diuresis for treating stranguria syndrome with Herba Taraxaci, Cortex Phellodendri, Ramulus Et Folium Picrasmae, and full side's compatibility has the effect of heat-clearing and toxic substances removing, the clear pouring of diuresis.
Preclinical pharmacology studies show that a kind of medicine for the treatment of nongonococcal urethritis of the present invention has functions such as good antiinflammatory, antibiotic, enhance immunity, inhibition bladder contraction and diuresis, analgesia.
One. the research of technology condition
1. the selection of dosage form
We are compound Chinese medicinal preparation, have heat-clearing and toxic substances removing, damp eliminating, inducing diuresis for treating stranguria syndrome, effect such as antibiotic.In order to give full play to the curative effect of medicine, adapt to the requirement of modern novel form and according to this recipe quantity size, we plan this product and are developed into the bigger special-shaped tablets of drug loading.It has, and dosage is accurate, and steady quality is easily controlled, bioavailability better and production technology level than characteristics such as height, and meet the requirement of preparation " five convenience "; This product is pressed into special-shaped tablets in addition, can improve the outward appearance of tablet, more easily accepts.So this product is developed into tablet.
2. technology condition research
(1) investigation of four flavor extraction conditions such as Rhizoma Smilacis Bockii
Rhizoma Smilacis Bockii, Herba Taraxaci, Ramulus Et Folium Picrasmae, Herba Desmodii Styracifolii are extracted with ethanol, serve as to investigate factor with concentration of alcohol, ethanol consumption, extraction time and extraction time, with L
9(3
4) orthogonal test table tests, and is the integrated survey index with the product of extractum yield and Chinaroot Greenbier Rhizome saponin content.
Demonstration test result is consistent with Orthogonal experiment results, and repeatability better, so determine that final process program is A
2B
2C
2, i.e. the optimum extraction conditions of four flavors such as Rhizoma Smilacis Bockii: etoh solvent concentration 70%, ethanol consumption are 16 times of medical material weight, and extraction time is 2 times, 2 hours for the first time; 1 hour for the second time.
(2) research of Caulis Fibraureae, Cortex Phellodendri extraction conditions
Because Caulis Fibraureae, the main effective ingredient of Cortex Phellodendri are alkaloids, and its content is all higher, the method that we intend adopting acid to carry alkali deposited is extracted, is made with extra care.Promptly adopt dilution heat of sulfuric acid to flood, impregnation liquid transfers PH to alkalescence with 20% sodium hydroxide solution, adds the chlorination sodium salt again and analyses, and placement is spent the night, and is centrifugal, and the precipitation oven dry promptly.We have designed quadrature factor level table on this basis, with L
9(3
4) orthogonal test table is tested, and is the integrated survey index with the product that precipitates yield and palmatine hydrochloride content.
Demonstration test result is consistent with Orthogonal experiment results, so determine that final process program is A
1B
2C
3D
2Promptly flood with concentration 0.2% sulfuric acid solution, 48 hours for the first time, 12 hours for the second time, 12 hours for the third time, filter respectively, merging filtrate is transferred pH to 9 with 20% sodium hydroxide solution, adds 8% sodium chloride again, and stirring is left standstill 24 hours, and is centrifugal, must precipitate oven dry.
(3) separation, purification, concentrated, drying process Study on Conditions
The different dry drying method is to the research of effective ingredient influence
1. the different dry drying method is to the influence of Chinaroot Greenbier Rhizome saponin content
Getting four Chinese medicine materials such as Rhizoma Smilacis Bockii, Herba Taraxaci extracts by preferred optimised process, concentrate, get concentrated solution 175ml (being equivalent to crude drug 175g), take by weighing 3 parts respectively, respectively place the 250ml evaporating dish, carry out drying respectively at drying under reduced pressure (60 ℃), drying under reduced pressure (90 ℃), constant pressure and dry, be dried to constant weight, get xeraphium and measure content.The result shows that drying under reduced pressure (60 ℃) effect is better than other method.
2. the different dry drying method is to the influence of palmatine hydrochloride content
Take by weighing Caulis Fibraureae 200g, Cortex Phellodendri 100g3 part respectively, in the round-bottomed flask respectively at 5000ml, test by the optimised process of screening.Carry out drying respectively at drying under reduced pressure (60 ℃), drying under reduced pressure (90 ℃), constant pressure and dry, be dried to constant weight, get xeraphium and measure content.The result shows that constant pressure and dry is better than other method to Caulis Fibraureae, Cortex Phellodendri drying effect.
(4) research of preparations shaping technology
1. the selection of the definite and kind of adjuvant amount
Learn according to above extraction process partial data: four flavor ultimate yields such as Rhizoma Smilacis Bockii, Herba Taraxaci are 10.7%; Caulis Fibraureae, Cortex Phellodendri ultimate yield are 2.5%.Because a day dose is a 50g crude drug amount, it is 4.12g that this day is obeyed the extractum amount.We intend making 12 of day clothes, the special-shaped Film coated tablets of every 0.5g.So need add the adjuvant amount in the medicine of taking every day is 1.88g (comprising the coating solution recruitment).Because it is less that this product adds adjuvant amount ratio, be developed into special-shaped Film coated tablets,, so both can have ensured tablet disintegrate in the time limit of regulation so require the amount of its binding agent, disintegrating agent bigger, can guarantee that again the plain sheet that is pressed into has certain rigidity, is beneficial to tablet coating.Still selected disintegrating property preferably carboxymethyl starch sodium and with the starch of bonding, disintegrate, diluting effect as the molding adjuvant; Pulvis Talci is as lubricant.
The selection of the condition of 2. granulating
With raw material pulverizing, cross 80 mesh sieves, mixing stirs evenly, (we are through preliminary experiment repeatedly to add certain proportion of starch and carboxymethyl starch sodium, the ratio of finding starch and carboxymethyl starch sodium is that 2: 3 o'clock effects are relatively good), add different wetting agent (95% ethanol, 50% ethanol, distilled water) and binding agent respectively, 16 orders are granulated, dry under 60-70 ℃, 16 order granulate, gained granule are used the single punch tablet machine tabletting after adding the lubricant mixing, through test of many times and demonstration test, demonstration test result is consistent with the trial test result, and tablet appearance U.S., easily accepts.So the ratio that definite final process program is starch and carboxymethyl starch sodium is 2: 3.Concentration is 50% alcoholic solution moistening, granulates, and the Pulvis Talci addition is the 0.7%-0.8% of Chinese crude drug extract total amount, is converted into 0.5% of semi-finished product total amount.
3. the research of tabletting, coating conditions
We will and have certain degree of hardness through compacting, nonabradable substrate carries out film coating, and it is better to find to make the Film coated tablets effect with Opadry (OPADRY) thin film coating material that blocks the production of happy Kanggong department.Because its influence factor is many in the film coating process, we intend adopting the method for orthogonal experiment that its consumption is screened, promptly with concentration, gun spraying speed and the plain sheet hardness of coating solution as the investigation factor, with L
9(3
4) orthogonal test table tests, with disintegration of tablet, coating qualification rate as investigating index.According to [Chinese Pharmacopoeia] tablet item regulation of following disintegration, Film coated tablets must all disintegrates in 1 hour.It is defective that we stipulate that then be judged to above 50 minutes its disintegration, so be important investigation index disintegration, adopting the method for overall merit is 2 with its coefficient settings; Coating qualification rate coefficient settings is 1.
The preparation of coating solution: the ethanol with 95% is added in the beaker, to 2/3 place of beaker height.Start constant temperature blender with magnetic force, make pure liquid keep uniform temperature and rotating speed, Opadry powder (model is 65G62830) is added in the ethanol liquid with isostatic speed, reinforced process should be finished in 5 minutes.Be mixed with certain density Opadry solution, reinforced finishing continues to stir, and makes whole solution keep rotation.
The mensuration of tablet hardness: the tablet that overregulates pressure and be pressed into of learning from else's experience places the tablet hardness analyzer to measure its hardness.
Test method: label after will sieving drops in the coating pan, intermittently feeds temperature filtration hot-air pre-heating to 38 ℃, opens spray gun and also regulates spray velocity and pressure, and film is sprayed perpendicular to material in 1/3 place on the plain sheet that rotates, and the coating pan rotating speed is kept 9r/min.Simultaneously, it is moderate to adjust hot blast, and the tablet temperature is remained on about 37 ℃.After coating was finished, the tablet that coating is good continued the blowing hot-air dry solidification, and gets final product after the coating solvent is volatilized.
The mensuration of disintegration: the tablet that pressure makes is measured according to [Chinese Pharmacopoeia] 2000 editions one appendix XIIA inspection technique disintegration.
Through orthogonal test and demonstration test, the result shows: with A
2B
1C
2Be best of breed, its good reproducibility is with the Orthogonal experiment results basically identical.Be that coating solution concentration is 14%, the gun spraying flow velocity is 0.12 (kg/min), and hardness is 5-6 (kg/mm
2).
Medicine of the present invention is according to its used medical material name and indication, and the two rattans of called after are drenched sheet clearly.
Two. the pharmaceutical research data
(1) pharmacodynamics test
It is compound Chinese medicinal preparation that two rattans are drenched sheet clearly, has the effect of heat-clearing and toxic substances removing, inducing diuresis for treating stranguria syndrome, the clinical treatment that is used for acute and chronic urethritis of non-gonococcal etc.
1. in-vitro antibacterial test
The effect of drenching sheet clearly according to two rattans with cure mainly, according to the principle and the method for " study of tcm new drug guide ", we drench sheet clearly to two rattans and have carried out antibiotic, antiinflammatory, diuresis, analgesic and analgesia etc. and cure mainly relevant Pharmacodynamic test of active extract research with function.Result of study shows, two rattans drench clearly that sheet is external to be had than obvious suppression and deactivation urinary tract infection common bacteria colon bacillus, staphylococcus aureus, Pseudomonas aeruginosa, staphylococcus epidermidis, streptococcus pyogenes, acinetobacter calcoaceticus, streptococcus faecalis, gonococcus, Bacillus proteus, Salmonella enteritidis, saccharomyces albicans, and changing pH and bacterial load does not influence two rattans and drench the antibacterial action of sheet to colon bacillus and staphylococcus epidermidis clearly;
Two rattans are drenched sheet clearly all to be had than obvious suppression and deactivation the type strain of testing selected colon bacillus, staphylococcus aureus, Pseudomonas aeruginosa, staphylococcus epidermidis, streptococcus pyogenes, acinetobacter calcoaceticus, streptococcus faecalis, gonococcus, Bacillus proteus, Salmonella enteritidis, saccharomyces albicans.Result of the test shows, two rattans are drenched sheet clearly all has certain inhibition and deactivation to testing 448 selected strain clinical isolates strains, and its MBC (the corresponding minimum drug level in no bacterial growth inoculation zone) is 2～4 times of MIC (contained minimum drug level in the no bacterial growth hole).
2. antibacterial tests in the body
With reference to " antibacterial tests principle in the body " and " herbal pharmacology research methodology " in " Ministry of Public Health bureau of drug administration new drug preclinical study instructs "; adopt the Sun Shi synthetic method to measure two rattans and drench the half protective number of sheet clearly, calculate its 95% fiducial limit colon bacillus ATCC25922 strain, staphylococcus epidermidis ATCC26069 strain infecting mouse.
(1) mensuration of test organisms minimum lethal dose
With ICR mice random packet, 10 every group, male and female half and half.Test organisms liquid is diluted with 10 times of continuous gradients of the normal saline that contains 5% gastric Mucin, infect one group of mice with each dilution bacterium liquid lumbar injection, infective dose 0.5ml/20g, with 5% gastric Mucin normal saline is contrast, observed 7 days, the dead mouse situation respectively organized in record, so that the whole dead Cmin amount of bacteria of mice are as minimum lethal dose (MLD).The result shows, the minimum lethal dose 1.25 * 10 of colon bacillus ATCC25922 strain and staphylococcus epidermidis ATCC26069 strain
8CFU/kg.
(2) two rattans are drenched sheet clearly to infecting mouse 0% (ED
0) and 100% (ED
100) mensuration of protective number
ICR mice random packet, 10 every group, male and female half and half.With test organisms 100%MLD lumbar injection infecting mouse, infect back 6h and begin administration.Two rattans are drenched sheet clearly to begin to do 5 times of continuous gradient dilutions with normal saline by 20%, one group of mice of each dilution factor medicinal liquid gastric infusion, 0.5ml/20g (initial dosage 60.6795g crude drug/kg), every day 1 time, continuous 7 days, set up simultaneously and infect contrast and normal control group, observe dead mouse situation in 7 days.The all dead maximum dosage-feeding of mice is 0% protective number, and the mice all minimum dosage of survival is 100% protective number.The result shows that two rattans are drenched the ED of sheet to colon bacillus ATCC25922 strain infecting mouse clearly
100Be 12.1359g crude drug/kg, ED
0Be 0.4854g crude drug/kg; ED to epidermis staphylococcus A TCC26069 strain infecting mouse
100Be 2.4272g crude drug/kg, ED
0Be 0.0971g crude drug/kg.
(3) two rattans are drenched the sheet subsides clearly to colon bacillus ATCC25922 strain and staphylococcus epidermidis ATCC26069 strain infecting mouse 50% (ED
50) mensuration of protective number
ICR mice random packet, 10 every group, male and female half and half.With colon bacillus ATCC25922 strain and staphylococcus epidermidis ATCC26069 strain 100%MLD bacterium liquid lumbar injection infecting mouse, set up simultaneously and infect matched group and normal control group, infect back 6h and begin administration.Two rattans are drenched sheet clearly uses normal saline by ED
100Begin to do the continuous gradient dilution: the initial dose to colon bacillus ATCC25922 strain infecting mouse is 12.1359g crude drug/kg, and the dilution gradient is 1: 0.6; Initial dose to epidermis staphylococcus A TCC26069 strain infecting mouse is 2.4272g crude drug/kg, and the dilution gradient is 1: 0.7.Do 6 gradients altogether, one group of mice of each gradient medicinal liquid gastric infusion.Dosage 0.5ml/20g, every day 1 time, continuous 7 days.Infect matched group and normal control group and give the isometric(al) normal saline with method.Observe dead mouse situation in 7 days, calculate two rattans and drench the ED of sheet clearly colon bacillus ATCC25922 strain and staphylococcus epidermidis ATCC26069 strain infecting mouse
50And 95% fiducial limit.
The result shows that two rattans are drenched sheet clearly has protective effect to colon bacillus and staphylococcus epidermidis infecting mouse; ED to colon bacillus ATCC25922 strain infecting mouse
50Be 4.8402g crude drug/kg, 95% credible 3.7299～6.2817g crude drug/kg that is limited to; ED to epidermis staphylococcus A TCC26069 strain infecting mouse
50Be 0.8889g crude drug/kg, 95% credible 0.7285～1.0849g crude drug/kg that is limited to.
3. to the influence of urinary tract infection model
60 of rats are divided into 6 groups at random, 10 every group.First group is the normal control group, gives the isometric(al) normal saline; Second group is model control group, gives the isometric(al) normal saline; The 3rd group of positive matched group given SANJIN PIAN 3.8g/kg; Fourth, fifth, six groups is that two rattans are drenched the sheet group clearly, drenches sheet 7,14,28g crude drug/kg clearly for respectively two rattans.Except that the normal control group, prohibited water 16 hours before all the other each treated animal operations, prepare the urinary tract infection model by list of references.Under the shallow fiber crops of ether, conventional fixing, the cropping sterilization in hypogastric region medisection skin and stomach wall, exposes the abdominal cavity, is threaded a needle to posterior abdominal wall place side respectively by both sides, left kidney ureter stage casing with the angular pin of wearing No. 4 lines, and silk thread two is drawn outside the stomach wall.(concentration is 5 * 10 to intravesical injection 0.8ml escherichia coli liquid then
8Individual/ml).Postoperative short-time characteristic ligation ureter is sewed up the incision, and recovers normally to raise.Postoperative removed the ureter ligature in 24 hours.Began gastric infusion, every day 1 time, continuous 7 days the same day from performing the operation.Put to death rat on the 8th day, and from bladder, extracted the 0.2ml urine, detect escherichia coli positive rate in the urine; Extract the bilateral kidney, weigh; Get kidney homogenate, detect nephridial tissue escherichia coli positive rate.The results are shown in Table 1.Table 1 pair rattan is drenched sheet clearly to the influence of urinary tract infection rat model (x ± s)
| Group | Dosage (g/kg) | Number of animals (only) | Kidney weight (g) | Escherichia coli positive rate (%) | |
| Nephridial tissue | Urine | ||||
| The two rattans of normal control group model matched group SANJIN PIAN are drenched the low dose of two rattans of sheet clearly and drench in the sheet the two rattans of dosage clearly and drench the sheet heavy dose clearly | 3.8 7 14 28 | 10 10 10 10 10 10 | 1.32±0.08** 1.56±0.25 1.34±0.10* 1.46±0.12 1.39±0.10 1.36±0.13* | 0* 100 60* 70 60* 40* | 0* 100 60* 70 60* 40* |
Compare * P＜0.05, * * P＜0.01 with model control group
By table 1 as seen, urinary tract infection rat model kidney weight increases, and the escherichia coli positive rate is 100% in nephridial tissue and the urine, with the normal control group significant difference (P＜0.01) is arranged more all, and the success of urinary tract infection model is described.Two rattans are drenched sheet clearly can alleviate urinary tract infection rat model kidney weight, reduce escherichia coli positive rate in nephridial tissue and the urine, with model control group relatively, in, heavy dose of group has significant difference (P＜0.01), illustrate that pair rattans drench sheet clearly and can effectively alleviate the urinary tract infection of rat.The positive control drug SANJIN PIAN also can effectively alleviate the urinary tract infection of rat.
4. antiinflammatory test
(1) acute abdominal cavity exudative inflammation test
50 of mices, male and female half and half are divided into 5 groups at random, 10 every group.First group of negative matched group given the isometric(al) normal saline; Second group of positive matched group given prednisone sheet 10mg/kg; Third and fourth, five groups drench the sheet group clearly for two rattans, drench sheet 10,20,40g crude drug/kg clearly for respectively two rattans.Each organizes all gastric infusions, 0.2ml/10g, and every day 1 time, for three days on end.Behind the last administration 1h, every Mus intravenous injection 0.5% azovan blue solution 0.1ml/10g, lumbar injection 0.6% acetic acid 0.2ml/ only then, the cervical vertebra dislocation is put to death behind the 20min, cut off the abdominal cavity, with 6ml normal saline gradation flushing abdominal cavity, collect cleaning mixture and add normal saline to 10ml, the centrifugal 15min of 3000rpm.Get supernatant in the 590nm colorimetric, calculate azovan blue content by standard curve.The results are shown in Table 2.
Table 2 pair rattan is drenched sheet clearly to the influence of chmice acute abdominal cavity exudative inflammation (x ± s)
| Group | Dosage (g/kg) | Number of animals (only) | Azovan blue amount (μ g/ml) | Suppression ratio (%) |
| The two rattans of negative control group prednisone sheet are drenched the low dose of two rattans of sheet clearly and drench in the sheet the two rattans of dosage clearly and drench the sheet heavy dose clearly | 0.01 10 20 40 | 10 10 10 10 10 | 0.18±0.02 0.10±0.01** 0.13±0.01** 0.12±0.01** 0.11±0.01** | 44.44 27.78 33.33 38.89 |
Compare * * P＜0.01 with negative control group
By table 2 as seen, two rattans are drenched sheet clearly can make mouse peritoneal azovan blue seepage discharge reduce, and compares with negative control group, and each dosage group all has significant difference (P＜0.01), and the two rattans of prompting are drenched sheet clearly can suppress the chmice acute exudative inflammation reaction that acetic acid stimulates.Positive control drug prednisone sheet also can suppress the chmice acute exudative inflammation reaction that acetic acid stimulates.
(2) rat acute exudative inflammation test
50 of rats are divided into 5 groups at random, 10 every group.First group of negative matched group given the isometric(al) normal saline; Second group of positive matched group given prednisone sheet 8mg/kg; Third and fourth, five groups drench the sheet group clearly for two rattans, drench sheet 7,14,28g crude drug/kg clearly for respectively two rattans.Each organizes gastric infusion, every day 1 time, and 1ml/100g, for three days on end.Behind the last administration 1h, the right back sufficient sole of the foot intradermal injection 10% Ovum Gallus domesticus album 0.1ml of every Mus causes inflammation.Cause scorching before and cause scorching back 30min, 1h, 2h, 4h measure the right back sufficient pawl volume of rat with rat toes volume determination instrument so that before and after scorching the difference of sufficient pawl volume as the swelling degree.
Result of the test shows, two rattans are drenched generation and the development that sheet can suppress the rat acute inflammation that Ovum Gallus domesticus album brings out clearly, compare with negative control group, 1h and 4h have significant difference (P＜0.05) behind the middle dosed administration, and 30min, 1h, 2h, 4h all have significant difference (P＜0.05 or P＜0.01) after the administration of heavy dose of group.Illustrate that two rattans drench sheet clearly Chinese People's Anti-Japanese Military and Political College's Mus acute exudative inflammation effect is arranged.Positive control drug prednisone sheet also can suppress the rat acute exudative inflammation reaction that Ovum Gallus domesticus album brings out.
(3) rat chronic proliferative inflammation test
50 of rats are divided into 5 groups at random, 10 every group.First group of negative matched group given the isometric(al) normal saline; Second group of positive matched group given prednisone sheet 5mg/kg; Third and fourth, five groups drench the sheet group clearly for two rattans, drench sheet 7,14,28g crude drug/kg clearly for respectively two rattans.Under the shallow fiber crops of ether, the cropping sterilization, in hypogastric region medisection skin, it is subcutaneous that the sterilization cotton balls of heavy 30mg is implanted the both sides groin, and skin suture is sterilized then, and whole process is the sterile working.From the preceding 3 days beginning gastric infusions of performing the operation, every day 1 time, continuous 10 days.Put to death rat on the 11st day, and carefully peeled off the granulation tissue of taking out cotton balls and parcel, 60 ℃ of dryings were weighed after 12 hours, deducted the raw cotton ball weight and were granulation tissue weight, and the result is expressed as the contained granulation tissue weight of every 100g body weight (bilateral).Represent the chronic inflammatory disease degree with granulation tissue weight, the results are shown in Table 3.
Table 3 pair rattan is drenched sheet clearly to the influence of rat chronic proliferative inflammation (x ± s)
| Group | Dosage (g/kg) | Number of animals (only) | Granulation tissue weight (mg/100g body weight) | Suppression ratio (%) |
| The two rattans of negative control group prednisone sheet are drenched the low dose of two rattans of sheet clearly and drench in the sheet the two rattans of dosage clearly and drench the sheet heavy dose clearly | 0.005 7 14 28 | 10 10 10 10 10 | 70.85±17.13 41.47±9.80** 70.15±10.03 56.10±13.90* 50.04±15.04** | 41.47 0.99 20.82 29.37 |
Compare * P＜0.05, * * P＜0.01 with negative control group
By table 3 as seen, two rattans are drenched sheet clearly and suppress the rat granulation tissue hyperplasia that cotton balls stimulates, and alleviate the weight of granulation tissue, compare with negative control group, in, heavy dose of group has significant difference (P＜0.05 or P＜0.01), illustrate that pair rattans drench sheet clearly the rat chronic proliferative inflammation is had inhibitory action.Positive control drug prednisone sheet also can suppress the rat granulation tissue hyperplasia that cotton balls stimulates.
5. diuretic test
40 of healthy rabbits are divided into 5 groups at random, 8 every group.First group of negative matched group given the isometric(al) normal saline; Second group of positive matched group, give hydrochlorothiazide tablet 2.8mg/kg, third and fourth, five groups drench the sheet group clearly for two rattans, drench sheet 3.64,7.28,14.56g crude drug/kg clearly for respectively two rattans.Load at first for rabbit with water, 30ml/kg, intravenous injection 3% pentobarbital sodium 1ml/kg anesthesia is then lain on the back and is fixed in operating-table, cuts off the hypogastric region hair, does being about the 5cm otch above pubic symphysis along median line, opens the abdominal cavity, exposes bladder.Cut bladder then, insert, fixedly the bladder funnel is with the collection urine.Operation finishes the back and stops 20min, collects 30min urine amount (before the administration) then.Gastric infusion, 5ml/kg.Begin to collect the urine amount after the administration, totally 4 times (the 1st 30～60min, 60～90min for the second time, 90～120min for the third time, the 4th time 120～150min), each 30min.The results are shown in Table 4.
Table 4 pair rattan is drenched sheet clearly to the diuresis of normal rabbits (x ± s)
| Group | Dosage (g/kg) | Number of animals (only) | Urine amount (ml) | ||||
| Before the administration | 30min after the administration | 60min | 90min | 120min | |||
| The two rattans of negative control group hydrochlorothiazide tablet are drenched the low dose of two rattans of sheet clearly and drench in the sheet the two rattans of dosage clearly and drench the sheet heavy dose clearly | 0.0028 3.64 7.28 14.56 | 8 8 8 8 8 | 3.44±1.31 3.51±2.14 3.36±1.22 3.20±2.07 3.49±2.06 | 5.09±2.84 5.43±3.35 5.34±1.81 5.61±3.92 11.95±6.67* | 5.66±2.22 9.59±4.14* 4.29±2.04 6.53±6.95 10.56±3.82** | 4.59±2.26 9.48±4.14* 4.83±3.50 3.43±2.54 7.51±2.93* | 5.08±3.22 7.85±3.92 3.63±2.59 3.09±2.03 6.79±7.53 |
Compare * P＜0.05, * * P＜0.01 with negative control group
By table 4 as seen, two rattans are drenched the urine amount that sheet can increase normal rabbits clearly, compare with negative control group, and 30min, 60min, 90min all have significant difference (P＜0.05 or P＜0.01) after the administration of heavy dose of group, and the two rattans of prompting are drenched sheet clearly rabbit is had diuresis.The positive control drug hydrochlorothiazide tablet also has diuresis to rabbit.
6. analgesic test
50 of mices, male and female half and half are divided into 5 groups at random, 10 every group.First group of negative matched group given the isometric(al) normal saline; Second group of positive matched group given aspirin tablet 0.2g/kg; Third and fourth, five groups drench the sheet group clearly for two rattans, drench sheet 10,20,40g crude drug/kg clearly for respectively two rattans.Each organizes all gastric infusions, 0.2ml/10g, and every day 1 time, for three days on end.Last administration 1h pneumoretroperitoneum is injected 1% acetum 0.1ml/10g, mouse writhing reaction (abdominal part pastes ground, indent, stretching, extension hind leg, distortion) number of times in the observed and recorded 15min.
Result of the test shows that two rattans are drenched sheet clearly and suppress the mouse writhing reaction that acetic acid stimulates, and compare with negative control group, and each dosage group all has significant difference (P＜0.01), and the pain that the two rattans of prompting are drenched the sheet Dichlorodiphenyl Acetate clearly to be stimulated has analgesic activity.The positive control drug aspirin tablet also can suppress the mouse writhing reaction that acetic acid stimulates.
7. separate heat test
48 of rabbit, male and female half and half are divided into 6 groups at random, 8 every group.First group is the normal control group, irritates stomach and gives isometric(al) (1ml/kg) normal saline; Second group is the fever model matched group, irritates stomach and gives the isometric(al) normal saline; The 3rd group of positive matched group, intramuscular injection injection of Radix Bupleuri 0.5ml/kg; Fourth, fifth, six groups is that two rattans are drenched the sheet group clearly, irritates stomach respectively and drenches sheet 3.64,7.28,14.56g crude drug/kg clearly for two rattans.Each rabbit is fixed, and measures the anus temperature 2 times, with meansigma methods as normal body temperature.Then, except that normal control group intravenous injection isometric(al) normal saline, all the other respectively organize auricular vein injection typhoid fever, paratyphoid fever bacterium liquid 1ml/kg makes fever model, and take temperature behind the 1.5h selects fervescence person's random packet more than 1 ℃.Each group is pressed above-mentioned dosed administration 1 time, and 30min, 1h, 2h, 4h measure rabbit anus temperature respectively after the administration.
Result of the test shows that typhoid fever, paratyphoid fever bacterium liquid can cause that rabbit body temperature obviously raises, and compares with normal body temperature self, and statistics has significant difference (P＜0.01); Two rattans are drenched sheet clearly and can reduce the rabbit body temperature that typhoid fever, paratyphoid fever bacterium liquid cause and raise, compare with the model control group of identical time, 1h, 2h, 4h all have significant difference (P＜0.05 or P＜0.01) after the administration of heavy dose of group, illustrates that pair rattans drench sheet clearly the rabbit infective fever is had refrigeration function.The positive control drug injection of Radix Bupleuri also has refrigeration function to the rabbit infective fever.
8. conclusion (of pressure testing)
Two rattans drench clearly that sheet is external to be had than obvious suppression and deactivation urinary tract infection common bacteria colon bacillus, staphylococcus aureus, Pseudomonas aeruginosa, staphylococcus epidermidis, streptococcus pyogenes, acinetobacter calcoaceticus, streptococcus faecalis, gonococcus, Bacillus proteus, Salmonella enteritidis, saccharomyces albicans, and changing pH and bacterial load does not influence two rattans and drench the antibacterial action of sheet to colon bacillus and staphylococcus epidermidis clearly; In the gastric infusion, body colon bacillus and staphylococcus epidermidis infecting mouse there is protective effect.Two rattans are drenched the sheet gastric infusion clearly, alleviate urinary tract infection rat model kidney weight, reduce escherichia coli positive rate in nephridial tissue and the urine; Suppress the rat acute inflammatory reaction that the chmice acute exudative inflammation reacts, Ovum Gallus domesticus album brings out of acetic acid stimulation and the rat chronic proliferative inflammation reaction that cotton balls stimulates; Suppress the mouse writhing reaction that acetic acid stimulates; Rabbit had diuresis and refrigeration function.Presentation of results, two rattans drench sheet clearly and have antibiotic, antiinflammatory, diuresis, analgesia, refrigeration function.
(2) two rattans are drenched the sheet animal acute toxicity test clearly
It is compound Chinese medicinal preparation that two rattans are drenched sheet clearly, has the effect of heat-clearing and toxic substances removing, inducing diuresis for treating stranguria syndrome, the clinical treatment that is used for acute and chronic urethritis of non-gonococcal etc.According to the specification requirement of new Chinese medicine toxicologic study, this experimental study two rattans drench the acute toxicity of sheet clearly.The result shows that two rattans are not found obvious acute toxicity after drenching the administration of sheet mouse stomach clearly, and mice maximum dosage-feeding on the one is 388.44g crude drug/kg, is equivalent to 466.1 times of clinical adult's consumptions every day.
(3) two rattans are drenched the sheet long-term toxicity test for animals clearly
It is compound Chinese medicinal preparation that two rattans are drenched sheet clearly, has the effect of heat-clearing and toxic substances removing, inducing diuresis for treating stranguria syndrome, the clinical treatment that is used for acute and chronic urethritis of non-gonococcal etc.Be 2～3 weeks the course of treatment.Drench the clinical course of treatment of sheet clearly according to two rattans, according to the specification requirement of new Chinese medicine toxicologic study, this experimental study two rattans drench sheet clearly to three months of rat (clinical course of treatment 4～6 times) long term toxicities.The result shows, with two rattans drench clearly large, medium and small three dosage of sheet (66.664,33.332,16.666g crude drug/kg, 80,40,20 times of consumption are equivalent to respectively to be grown up) give rat continuous irrigation stomach three months, general situation, hematology, blood biochemical, routine urinalysis, electrocardiogram, system's dissection, organ coefficient and histopathology to rat all do not have obvious influence, do not find toxic reaction, convalescent period does not also have the retardance toxic reaction, and it is 66.664g crude drug/kg/ day that rat non-toxic reaction dosage is provided.
Preparation embodiment
Embodiment 1
Prescription:
Caulis Fibraureae 833g Rhizoma Smilacis Bockii 833g Herba Taraxaci 833g
Cortex Phellodendri 416g Ramulus Et Folium Picrasmae 416g Herba Desmodii Styracifolii 833g
Make 1000
Preparation method:
Get Rhizoma Smilacis Bockii, Herba Taraxaci, Ramulus Et Folium Picrasmae, Herba Desmodii Styracifolii by prescription and add 16 times of amount 70% alcohol reflux twice, 2 hours for the first time; 1 hour for the second time.Filter, merging filtrate, decompression filtrate recycling ethanol also is concentrated into the thick paste shape, and vacuum drying (60 ℃) is pulverized, and crosses 80 mesh sieves.
By prescription get Caulis Fibraureae, Cortex Phellodendri powder is broken into coarse powder, add 0.2% sulfuric acid solution and soak (amount of liquid just covers the medical material face), 48 hours for the first time; 12 hours for the second time, 12 hours for the third time.Filter, filtrate is transferred pH to 9 with 20% sodium hydroxide solution, adds 8% sodium chloride, stir, and standing over night, centrifugal, the precipitation oven dry promptly gets Caulis Fibraureae, Cortex Phellodendri extract, pulverizes, and crosses 80 mesh sieves.
Above two kinds of extracts are mixed, add starch 57g, carboxymethyl starch sodium 85g stirs evenly, and adds 50% ethanol moistening, with the granulation of 16 mesh sieves, granulate, adds Pulvis Talci 2.5g, mixing, and tabletting is with 14% Opadry (model is 65G62830) solution coating, promptly.
Embodiment 2
Prescription:
Caulis Fibraureae 4165g Rhizoma Smilacis Bockii 4165g Herba Taraxaci 4165g
Cortex Phellodendri 2080g Ramulus Et Folium Picrasmae 2080g Herba Desmodii Styracifolii 4165g
Make 5000
Preparation method:
Get Rhizoma Smilacis Bockii, Herba Taraxaci, Ramulus Et Folium Picrasmae, Herba Desmodii Styracifolii by prescription and add 16 times of amount 70% alcohol reflux twice, 2 hours for the first time; 1 hour for the second time.Filter, merging filtrate, decompression filtrate recycling ethanol also is concentrated into the thick paste shape, and vacuum drying (60 ℃) is pulverized, and crosses 80 mesh sieves.
By prescription get Caulis Fibraureae, Cortex Phellodendri powder is broken into coarse powder, add 0.2% sulfuric acid solution and soak (amount of liquid just covers the medical material face), 48 hours for the first time; 12 hours for the second time, 12 hours for the third time.Filter, filtrate is transferred pH to 9 with 20% sodium hydroxide solution, adds 8% sodium chloride, stir, and standing over night, centrifugal, the precipitation oven dry promptly gets Caulis Fibraureae, Cortex Phellodendri extract, pulverizes, and crosses 80 mesh sieves.
Above two kinds of extracts are mixed, add starch 285g, carboxymethyl starch sodium 425g stirs evenly, and adds 50% ethanol moistening, with the granulation of 16 mesh sieves, granulate, adds Pulvis Talci 12.5g, mixing, and tabletting is with 14% Opadry (model is 65G62830) solution coating, promptly.
Embodiment 3
Prescription:
Caulis Fibraureae 83.3kg Rhizoma Smilacis Bockii 83.3kg Herba Taraxaci 83.3kg
Cortex Phellodendri 41.6kg Ramulus Et Folium Picrasmae 41.6kg Herba Desmodii Styracifolii 83.3kg
Make 100000
Preparation method:
Get Rhizoma Smilacis Bockii, Herba Taraxaci, Ramulus Et Folium Picrasmae, Herba Desmodii Styracifolii by prescription and add 16 times of amount 70% alcohol reflux twice, 2 hours for the first time; 1 hour for the second time.Filter, merging filtrate, decompression filtrate recycling ethanol also is concentrated into the thick paste shape, and vacuum drying (60 ℃) is pulverized, and crosses 80 mesh sieves.
By prescription get Caulis Fibraureae, Cortex Phellodendri powder is broken into coarse powder, add 0.2% sulfuric acid solution and soak (amount of liquid just covers the medical material face), 48 hours for the first time; 12 hours for the second time, 12 hours for the third time.Filter, filtrate is transferred pH to 9 with 20% sodium hydroxide solution, adds 8% sodium chloride, stir, and standing over night, centrifugal, the precipitation oven dry promptly gets Caulis Fibraureae, Cortex Phellodendri extract, pulverizes, and crosses 80 mesh sieves.
Above two kinds of extracts are mixed, add starch 5.7kg, carboxymethyl starch sodium 8.5kg stirs evenly, and adds 50% ethanol moistening, with the granulation of 16 mesh sieves, granulate, adds Pulvis Talci 250g, mixing, and tabletting is with 14% Opadry (model is 65G62830) solution coating, promptly.
Claims (3)
1. medicine for the treatment of nongonococcal urethritis is characterized in that it is that Chinese crude drug by following prescription is prepared from through extract 2-2.2 weight portion and the 1 weight portion pharmaceutic adjuvant that extraction obtains.
Its Chinese crude drug prescription is:
Caulis Fibraureae 833g Rhizoma Smilacis Bockii 833g Herba Taraxaci 833g
Cortex Phellodendri 416g Ramulus Et Folium Picrasmae 416g Herba Desmodii Styracifolii 833g
Make 1000, its dosage form is special-shaped Film coated tablets.
Wherein pharmaceutic adjuvant comprises disintegrating agent carboxymethyl base Starch Sodium, binder starch, lubricant Pulvis Talci, wetting agent ethanol water, coating materials Opadry; Carboxymethyl starch sodium weight portion wherein: the starch weight portion is 3: 2.
2. according to a kind of medicine for the treatment of nongonococcal urethritis of claim 1, the consumption of described pharmaceutic adjuvant is in extract obtained weight portion:
The total amount 0.4 Pulvis Talci 0.007-0.008 of starch and carboxymethyl starch sodium.
3. according to a kind of medicine for the treatment of nongonococcal urethritis of claim 1, preparation method may further comprise the steps:
(1) gets Rhizoma Smilacis Bockii, Herba Taraxaci, Ramulus Et Folium Picrasmae, Herba Desmodii Styracifolii by recipe quantity and add 16 times of amount 70% alcohol reflux twice, 2 hours for the first time; 1 hour for the second time.Filter, merging filtrate, decompression filtrate recycling ethanol also is concentrated into the thick paste shape, vacuum drying, temperature is 60 ℃ when dry, pulverizes, and crosses 80 mesh sieves, gets the ethanol extract of Rhizoma Smilacis Bockii, Herba Taraxaci, Ramulus Et Folium Picrasmae, Herba Desmodii Styracifolii;
(2) by prescription measure Caulis Fibraureae, Cortex Phellodendri powder is broken into coarse powder, adds 0.2% sulfuric acid solution and soaks, amount of liquid just covers the medical material face, 48 hours for the first time; 12 hours for the second time, 12 hours for the third time.Filter, filtrate is transferred pH to 9 with 20% sodium hydroxide solution, adds 8% sodium chloride, stir, and standing over night, centrifugal, the precipitation oven dry is pulverized, and crosses 80 mesh sieves, promptly gets Caulis Fibraureae, Cortex Phellodendri extract;
(3) above two kinds of extracts are merged, mix, add starch, carboxymethyl starch sodium, stir evenly, adding concentration is an amount of moistening of 50% ethanol, with the granulation of 16 mesh sieves, granulate, add Pulvis Talci, mixing, tabletting is with 14% Opadry (model is 65G62830) solution coating, promptly.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104873754A (en) * | 2015-05-28 | 2015-09-02 | 王玉波 | Pregnant woman urinary tract infection treatment Chinese medicine |
| CN105878854A (en) * | 2014-11-20 | 2016-08-24 | 北京创立科创医药技术开发有限公司 | Traditional Chinese medicinal composition for treating non-gonococcal urethritis and preparation method of traditional Chinese medicinal composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1814211A (en) * | 2005-11-27 | 2006-08-09 | 干宝善 | Chinese herbal medicine decoction for treating acute icterohepatitis and preparing method |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105878854A (en) * | 2014-11-20 | 2016-08-24 | 北京创立科创医药技术开发有限公司 | Traditional Chinese medicinal composition for treating non-gonococcal urethritis and preparation method of traditional Chinese medicinal composition |
| CN105878854B (en) * | 2014-11-20 | 2019-12-17 | 北京创立科创医药技术开发有限公司 | Traditional Chinese medicine composition for treating non-gonococcal urethritis and preparation method thereof |
| CN104873754A (en) * | 2015-05-28 | 2015-09-02 | 王玉波 | Pregnant woman urinary tract infection treatment Chinese medicine |
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