Summary of the invention
The purpose of this invention is to provide and a kind ofly have good antiinflammatory, pain relieving, the effect of fossil calculus and can prevent that urinary stone from forming and recurrence, gonococcus be had the treatment urinary calculus of killing action and the pharmaceutical composition of urinary system infection disease.
The pharmaceutical composition of treatment diseases of urinary system of the present invention is the medicament of being made by following weight percentages and pharmaceutic adjuvant: Herba Desmodii Styracifolii 5-35, Endothelium Corneum Gigeriae Galli 2-8, Rhizoma Alismatis 5-15, husky cattle 0.5-1.5, succinum 1-5, Radix Astragali 5-15, Folium Pyrrosiae 5-35, Spora Lygodii 2-6, Semen Plantaginis 10-20, Radix Glycyrrhizae 1-3, Rhizoma Corydalis (processed with vinegar) 5-15.
In above-mentioned composition, better percentage by weight is: Herba Desmodii Styracifolii 18-22, Endothelium Corneum Gigeriae Galli 3-6, Rhizoma Alismatis 7-12, husky cattle 0.8-1.2, succinum 2-5, Radix Astragali 7-12, Folium Pyrrosiae 18-22, Spora Lygodii 2-5, Semen Plantaginis 12-17, Radix Glycyrrhizae 1-3, Rhizoma Corydalis (processed with vinegar) 7-12.
In the above-mentioned composition, Herba Desmodii Styracifolii, Rhizoma Alismatis, Semen Plantaginis diuresis, calculus; Radix Astragali diuresis, antibiotic; Succinum inducing diuresis for treating stranguria syndrome, activating blood and removing stasis; Folium Pyrrosiae diuresis, heat clearing away, hemostasis, antibiotic; Spora Lygodii clearing heat and freeing strangury, diuresis; Rhizoma Corydalis is invigorated blood circulation, is regulated the flow of vital energy, pain relieving; Husky cattle, the sensible diuretic of Endothelium Corneum Gigeriae Galli, softening the hard mass fossil.Each medicine share, and has inducing diuresis for treating stranguria syndrome, fossil calculus, anti-inflammation, the effect of pain relieving.
The production method of pharmaceutical composition of the present invention is as follows: the Chinese medicine Herba Desmodii Styracifolii is soaked the back decoct 2-5 time, collecting decoction filters, and filtrate is condensed into concentrated solution, and is standby; Endothelium Corneum Gigeriae Galli, Rhizoma Alismatis, husky cattle, succinum, the Radix Astragali, Folium Pyrrosiae, Spora Lygodii, Semen Plantaginis, Radix Glycyrrhizae, Rhizoma Corydalis (processed with vinegar) 10 flavor Chinese medicine powders are broken into fine powder, mix with above-mentioned concentrated solution, add adjuvant Mel, Radix Glycyrrhizae powdered carbon, Pulvis Talci, magnesium stearate and make corresponding oral formulations.Described Rhizoma Corydalis is a Rhizoma Corydalis (processed with vinegar), promptly gets clean Rhizoma Corydalis, boils altogether with vinegar, boils to solution to be exhausted fully, takes out drying.Every 100kg Rhizoma Corydalis vinegar 20kg.Rhizoma Corydalis (processed with vinegar) is a prior art.
Chinese traditional compound medicine of the present invention, through repeatedly prescription experiment, meet Chinese medicine prescription combination principle, complement each other can square full production effect for each medicine in the compound preparation, and stranguria, the difficulty in urination, urinary tract infection, lithangiuria, prostatitis, cystitis, pyelonephritis, chyluria etc. are had obvious therapeutic action and do not have obvious toxic-side effects.
Described pharmaceutical composition is an oral formulations, as: pill (comprising drop pill), tablet (comprising dispersible tablet, effervescent tablet, chewable tablet, coated tablet or the like), capsule (comprising soft capsule), powder, electuary.
The pharmacodynamics test of this pharmaceutical composition is as follows:
In vitro tests shows that this product has certain litholytic effect to the human body lithangiuria, and escherichia coli, paracolon, staphylococcus aureus, bacillus pyocyaneus are all had certain antibacterial action, and Bacillus proteus is had tangible antibacterial action; But its solution and pastille serum thereof, urine all do not have obvious influence to guinea pig in vitro smooth muscle of bladder tension force, also can not the antagonism acetylcholine to the excitation of smooth muscle of bladder.Bulk testing shows, this product is brought out kidney of rats calculus and foreign body to ethylene glycol and brought out the rat bladder knot sole of the foot certain inhibitory action is all arranged; The mice hot plate is caused pain certain analgesic activity, but writhing response does not have obvious influence due to the Dichlorodiphenyl Acetate; Rat paw edema all has certain inhibitory action due to Dichlorodiphenyl Acetate induced mice peritoneum inflammatory exudation and the carrageenin; The effect that increases the rat urine amount is arranged; The Bacillus proteus infecting mouse seemingly there is certain protection effect trend, but the coli-infection mice is not had obvious protective effect.
Test objective:
Observe the effects such as treating stranguria dampness removing, fossil pain relieving of this product by animal experiment, for its clinical practice provides the animal experiment foundation.
Be subjected to the reagent thing: present embodiment 4 obtained pills.
Clinical consumption is each clothes 5 balls, 3 times on the one, and 4 weeks of the course of treatment.The medicinal liquid that will be subjected to the reagent thing to be made into suitable concentration with deionized water during test supplies the animal gastric infusion, and each dosage group administration volume is equated.
Experiment material:
1, animal: Wistal is a rat, regular grade, and animal housing of this institute provides, the quality certification number " No. the 11001st, the moving word of osmanthus doctor ".The NIH white mice, regular grade, animal housing of this institute provides, the quality certification number " No. the 11002nd, the moving word of osmanthus doctor ".Cavia porcellus, regular grade, ♀ ♂ dual-purpose, body weight 400~500g, Guangxi Chinese medicine institute animal housing provides.Animal ♀ ♂ divide the cage group support, and automatic water-supply is raised, and feeds pellet.20~30 ℃ of laboratory temperatures (air-conditioning), relative humidity 60~85%.
2, medicine and reagent: JIESHITONG PIAN, Guangxi Wuzhou Pharmaceutical (group) limited company, crude drug 2g/Tab, lot number 990508-1.Acetylcholine, pharmaceutical factory, new Asia, Shanghai, lot number 650520.Rotundine Tablets, Guangdong Province Boluo pioneer Pharmaceutical group company, lot number 990601.Hydrochlorothiazide Tablet (DHCT), Jinzhou, Liaoning pharmaceutical factory, lot number 960301.Compound sulfamethoxazole tablet (TMP+SMZ), guilin pharmacy factory, lot number 980401.Norfloxacin capsule, South of Guangxi pharmacy group company, lot number 980310.Prednisone acetate tablets, South of Guangxi pharmacy group company, lot number 960522.Ethylene glycol ammonium chloride mixed fodder.0.7% acetum, 1% carrageenin suspension.The calcium determinating reagent box, Shanghai Rongsheng Bioisystech Co., Ltd, lot number 990901.Sterilization wooden stick (diameter 3mm, long 5mm is with 75% soak with ethanol 24h).The human body lithangiuria, first Pathology Deparment of Affiliated Hospital of Colleges Of Traditional Chinese Medicine Of Guangxi provides.
3, bacterial strain and culture medium: escherichia coli [CMCC (B) 44102], Bacillus proteus [CMCC (B) 49102], staphylococcus aureus [CMCC (B) 26003], bacillus pyocyaneus [CMCC (B) 10104], Nat'l Pharmaceutical ﹠ Biological Products Control Institute provides.Paracolon (clinical strain), Guangxi microorganism teaching and research room of health personnel administration institute provides.Nutrient broth medium, serum broth, nutrient agar, blood agar culture-medium, the antibiotic chamber preparation of this institute.
4, instrument: A120S type electronic analytical balance (1/10000g), German SARTORIUS company produces.MS-302 multimedization bio signal record analysis system, Guangdong Pharmaceutical University produces.JZ100 type muscle tone transducer, the Gaobeidian City mechanical ﹠ electronic equipment corporation, Ltd of newly navigating.The constant temperature hot plate causes the pain device, the assembling of pharmacological room of this institute.Mus foot GR grain capacity gross tubule measurement by magnification device, the assembling of pharmacological room of this institute.The semi-automatic analyzer of CHEM-5 type, Japanese ERBA company produces.
Experimental technique and result:
1, to the influence of rat ethanol renal calculus
Get 60 of ♂ rats, body weight 150~200g is divided into 6 groups at random, except that the normal control group, all does the moulding of ethylene glycol renal calculus for other 5 groups: feed continuous 37 days with ethylene glycol ammonium chloride mixed fodder.Ig administration in moulding: three groups are given and are subjected to the reagent thing, and positive controls is logical to calculus, and model control group and normal control group are given ordinary water, and every day 1 time, dosage sees Table 1, and the administration volume is 10ml/kg, continuous 37 days.Put to death rat next day after the last administration, cuts open to get two kidneys and do perusal; And do histopathologic examination after fixing, write down the degree of each Ren Mus calculus by following " standard ".Compare with model control group, the Ridit check the results are shown in Table 1 between the work group.
The pathologic finding grade scale: " one " renal cortex and medullary substance there is no calculus and crystallization deposition thing.The calculus crystallization deposition thing that as seen "+" renal cortex and medullary substance are dispersed on a small quantity, 1~3 the crystallization kitchen range in every low power (10 times) visual field." ++ " renal cortex and medullary substance visible calculus crystallization deposition thing or little free crystallization, 4~6 the crystallization kitchen ranges in every low power (10 times) visual field." +++" renal cortex and the visible more calculus crystallization deposition thing of medullary substance, and have calculus to form every low power (10 times) visual field 7~9 crystallization kitchen ranges.
Table 1 pair rat ethylene glycol renal calculus influence result (n=10)
As seen the result is subjected to the naked eyes of three dosage groups of reagent thing and histopathology lesion degree all less than model group, heavy dose of group naked eyes pathological changes and model group difference significance.Prompting this product is brought out the certain inhibitory action of being formed with of kidney of rats calculus to ethylene glycol.
2, to the cystolithic influence test of the rat opposite sex
]
Get 50 of ♂ rats, body weight 200~270g, be divided into 5 groups at random, every Mus all does the moulding of foreign body vesical calculus: the anesthesia of ip pentobarbital sodium, cut open the belly the sterilization wooden stick after weighing on the electronic balance is inserted intravesical and purse string suture bladder otch, penicillin sodium 80,000 U infection behind the lumbar injection when closing abdomen, postoperative is normally fed.Moulding begins the ig administration after 4 weeks: three groups are given and are subjected to the reagent thing, and positive controls is logical to calculus, and model control group is given ordinary water, and every day 1 time, dosage sees Table 1, and the administration volume is 10ml/kg, continuous 30 days.Put to death rat next day after the last administration, takes out the wooden stick of inserting bladder, weighs on electronic balance after 60 ℃ of 24h oven dry, deducts original rod and heavily be foreign body in bladder calculus weight, compares t check between the work group with the ordinary water group.The results are shown in Table 2.
The table 2 couple cystolithic result that influences of the rat opposite sex
Group |
Dosage (/kg) |
N |
Calculus weight (mg, X ± S) |
Be subjected to the reagent thing |
1.54g |
9 |
1.77±0.54
* |
Be subjected to the reagent thing |
0.77g |
10 |
2.05±1.33 |
Be subjected to the reagent thing |
0.38g |
10 |
2.03±0.67 |
Calculus is logical |
10g |
10 |
1.78±0.78 |
Ordinary water |
10ml |
10 |
2.42±0.61 |
Annotate:
*P<0.05,
*P<0.01, all the other p>0.05, down together
The result as seen, the calculus weight that is subjected to a large amount of agent groups of reagent thing is less than the ordinary water group, the difference significance.Prompting this product is brought out the rat bladder calculus to foreign body certain inhibitory action.
3, external lithodialysis (human body lithangiuria) test
]
, totally 45 manage in 1 branch harness of human body lithangiuria plug test tube of scales/electronic balance weighing, big or small basically identical.To be subjected to the reagent thing to be made into the medicinal liquid of three kinds of concentration, other prepares JIESHITONG PIAN contrast liquid, and establishes the deionized water contrast.The medicinal liquid of every kind of concentration is established 9 pipes, and liquor strength sees Table 3, and every pipe adds a certain amount of medicinal liquid (g: ml=1: 30), place 37 ℃ of waters bath with thermostatic control, each jolting 1 time (putting upside down 5 times) by calculus weight.Soak and take out calculus after 7 days, after 60 ℃ of 5h oven dry,, calculate the lithodialysis rate in scales/electronic balance weighing; Soak is got supernatant mensuration calcium content under semiautomatic biochemistry analyzer 630nm wavelength after centrifugal; Compare t check between the work group with the deionized water group.The results are shown in Table 3.
The external lithodialysis of table 3 (human body lithangiuria) result of the test (X ± S, n=9)
Group |
Concentration (crude drug g%) |
Weight (mg) before calculus is soaked |
Lithodialysis rate (%) |
Soak calcium content (mmol/L) |
Be subjected to the reagent thing |
76.9 |
82.7±45.3 |
2.3±3.3 |
1.076±0.406
* |
Be subjected to the reagent thing |
19.2 |
84.2±40.4 |
1.8±2.6 |
0.316±0.158 |
Calculus is logical |
100 |
84.3±41.9 |
1.9±2.3 |
1.179±0.750 |
Deionized water |
- |
81.3±38.3 |
5.4±8.3 |
0.598±0.439 |
As seen table 3 is subjected to the lithodialysis rate of three concentration liquids of reagent thing all close with deionized water, the difference nonsignificance; But the calcium content of high concentration soak is greater than deionized water, the difference significance.This product is external when high concentration the human body lithangiuria is had certain litholytic effect in prompting.
4, to the level and smooth tensile influence test of guinea pig in vitro bladder
Cavia porcellus from the execution of tapping the head, is cutd open immediately and gets bladder, place Tyrods ' s liquid, conventional preparation bladder muscle bar specimen.37 ± 0.5 ℃ of bath temperature, volume 50ml, conventional oxygen supply.Specimen one end is fixed in the groove on " L " shape steady arm, and the other end connects tonotransducer, gives certain load (1g), writes down its tension variation with MS-302 multimedization bio signal record analysis system.After treating the specimen tension stability, add successively and respectively test medicinal liquid, observe medicine the tensile influence of specimen.Each observation effect 5min, and wash bath three times, treat to do next medicinal liquid test again after specimen tension force recovers, stablizes.
Be subjected to the preparation of reagent liquid: 1. be subjected to reagent thing aqueous solution-get to be subjected to reagent thing medical material dried cream powder 5g, add deionized water dissolving, be assigned to 50ml (crude drug 768.7mg/ml).2. rat pastille (being subjected to the reagent thing) serum-give rat oral gavage with the dosage of 4g dried cream powder/kg, behind the 2h through the isolating serum of ventral aorta blood sampling.3. rat pastille (being subjected to the reagent thing) urine-give rat oral gavage with the dosage of 4g dried cream powder/kg, 2h is after the urine that bladder is gathered.
Test through 4 guinea pig in vitro bladder muscle bar specimen shows, above-mentioned three kinds specimen tension force is not all had obviously by reagent liquid to influence, also can not the antagonism acetylcholine to the excitation of specimen, prompting this product does not have obvious influence to Cavia porcellus smooth muscle of bladder tension force, no longer proceeds so test.
5, the influence test (writhing method) of Dichlorodiphenyl Acetate induced mice stomachache
Get 50 of mices, ♀ ♂ half and half, body weight 18~22g is divided into 5 groups at random.Three groups are given and are subjected to the reagent thing, and positive controls is given rotundine, and the blank group is given ordinary water, and dosage sees Table 5, and every day, the ig administration was 1 time, and the administration volume is 20ml/kg, successive administration 3 days.1h after the last administration, the equal ip0.7% acetic acid of each Mus 10ml/kg, and write down behind the equal ip acetic acid of each Mus of each Mus and to turn round the body number of times in the 15min, with the ordinary water group relatively, t check between the work group.The results are shown in Table 5.
Table 5 pair mice acetic acid causes the result that influences of pain
Group |
n |
Dosage (/kg) |
Turned round body number of times (X ± S) in 15 minutes |
Suppression ratio (%) |
Be subjected to the reagent thing |
10 |
3.00g |
23.1±10.4 |
2.5 |
Be subjected to the reagent thing |
10 |
1.50g |
19.5±9.12 |
17.7 |
Be subjected to the reagent thing |
10 |
0.75g |
19.8±10.2 |
16.5 |
Rotundine |
10 |
80mg |
5.7±3.13
** |
75.9 |
Ordinary water |
10 |
20ml |
23.7±15.2 |
|
The result as seen, what be subjected to the large, medium and small dosage group of reagent thing turns round body number of times and the equal nonsignificance of ordinary water difference.Prompting this product Dichlorodiphenyl Acetate induced mice stomachache does not have obviously influence.
6, mice hot plate piece is caused the influence test of pain
Get 50 of ♀ mices, body weight 18~21g, after causing the pain instrument and measure basis pain valve increment with the hot plate of 55 ± 0.5 ℃ of baseplate temps, be divided into 5 groups at random, ig administration immediately: three groups are given and are subjected to reagent thing crude drug dried cream powder, and positive controls is given rotundine, and the blank group is given ordinary water, dosage sees Table 6, and the administration volume is 20ml/kg.Respectively at measuring the pain threshold values of each Mus with method in 1,2,3 hour after the administration, the difference that deducts basic value with value behind the medicine as medicine after threshold of pain increment, with the ordinary water group relatively, do t check between group.The results are shown in Table 6.
Table 6 pair mice hot plate piece cause the pain influence the result (second, X ± S, n=10)
The result as seen, be subjected to the medicine of a large amount of dosage groups of reagent thing after threshold of pain increment in 3 hours greater than the ordinary water group, the difference significance.Prompting this product causes pain to the mice hot plate certain analgesia threshold effect.
7, the influence of Dichlorodiphenyl Acetate induced mice peritoneum inflammatory exudation test
Get 60 of mices, ♀ ♂ half and half, body weight 20~22g is 5 groups and ig administration at random: three groups are given and are subjected to reagent thing crude drug dried cream powder, positive controls is given prednisone, and the blank group is given ordinary water, and dosage sees Table 7, the administration volume is 20ml/kg, administration every day 1 time, for three days on end.After the last administration 1 hour, the equal iv0.5% azovan blue of each Mus normal saline solution 10ml/kg, and ip 0.7% acetic acid 10ml/kg immediately.15min puts to death mice behind ip acetic acid, use the normal saline flushing abdominal cavity, collect whole flushing liquors to 10ml, get supernatant after centrifugal and measure its 0D value in semi-automatic analyzer 630nm wavelength place, concentration with azovan blue in the 0D value representation flushing liquor, the degree of reflection peritoneum inflammatory exudation compares with the ordinary water group indirectly, does t check between group.The results are shown in Table 7.
Table 7 Dichlorodiphenyl Acetate induced mice peritoneum inflammatory exudation influence the result
Group |
n |
Dosage (/kg) |
0D(X±S) |
Suppression ratio (%) |
Be subjected to the reagent thing |
10 |
3.00g |
0.079±0.031
** |
50.5 |
Be subjected to the reagent thing |
10 |
1.50g |
0.108±0.044
* |
32.3 |
Be subjected to the reagent thing |
10 |
0.75g |
0.122±0.060 |
23.4 |
Prednisone |
10 |
20mg |
0.105±0.043
* |
33.9 |
Ordinary water |
10 |
20ml |
0.159±0.055 |
|
The result as seen, the 0D value that is subjected to three dosage groups of reagent thing is all less than the ordinary water group, big or middle dosage group and ordinary water group difference have highly significant and remarkable meaning.Prompting this product Dichlorodiphenyl Acetate induced mice peritoneum inflammatory exudation has certain inhibitory action.
8, the influence test of rat foot stone swelling due to the on Carrageenan
Get 50 of ♂ rats, body weight 230~260g is 5 groups and ig administration at random: three groups are given and are subjected to reagent thing crude drug dried cream powder, positive controls is given prednisone, and the blank group is given ordinary water, and dosage sees Table 8, the administration volume is 10ml/kg, and every day, ig was administered once, continuous 4 days.Measured a right back sufficient volume of Mus on 4th and make normal value with the volumetric measurement method, ig administration immediately, and it is subcutaneous so that scorching to inject the right back sufficient sole of the foot of each Mus with 1% carrageenin by 50ul.Measured the right back sufficient volume of each Mus as causing scorching back value with method respectively in 2,4,6 hours behind the Yu Zhiyan, thus the difference of scorching back value and normal value as cause scorching after the swelling value, compare with the ordinary water group, do that t checks between group.The results are shown in Table 8.
Table 8 on Carrageenan cause rat organize the bullate result of influence (X ± S, n=10)
As seen the result is subjected to swelling value and the ordinary water group difference significance of the scorching back 4h of causing of the big dosage group of reagent thing.Rat paw edema has certain inhibitory action due to prompting this product on Carrageenan.
9. the influence of rat urine amount is tested
Get 40 of rats, ♀ ♂ half and half, body weight 220~260g divides 5 groups at random, and three groups are given and are subjected to reagent thing crude drug dried cream powder, and positive controls is given DHCT, and blank makes up to ordinary water, and dosage sees Table 9, and the administration volume is 10ml/kg, successive administration 3 days.Preceding 1 hour (prohibited and raised 15 hours) of last administration irritates stomach and gives normal saline 50ml/kg, and gently presses the rat hypogastric region to make the bladder emptying, prohibits and raises taboo water, promptly put after the last administration in the metabolic cage, collect 6 hours urine amount, and obtain the urine amount of every 100g body weight, with ordinary water group ratio, t check between the work group.The results are shown in Table 9.
Table 9 pair rat urine amount influence result (X ± S)
As seen the result is subjected to the heavy dose of 6 hours voided volume organizing of reagent thing greater than the ordinary water group, the difference significance.Prompting this product has the effect that increases the rat urine amount.
10. Chinese People's Anti-Japanese Military and Political College's enterobacteria infection experiment in the body
Get 50 of rats, body weight 18~22g, ♀ ♂ half and half divides 5 groups and ig administration at random; Three groups are given and are subjected to reagent thing crude drug dried cream powder, and positive controls is given norfloxacin, and the blank group is given ordinary water, and the administration volume is 20ml/kg, and dosage sees Table 10.All make microbiological contamination in the body: ip 10 after 1 hour in administration
7The escherichia coli of CFU/ml (bacterium number 44102, contain 2% dry yeast) bacterium liquid 25ml/kg.The death toll in 7 days after the mice microbiological contamination respectively organized in record, with the ordinary water group relatively, do to simplify the exact propability analysis.The results are shown in Table 10.
The intestinal infection experiment result of the Chinese People's Anti-Japanese Military and Political College in table 10 body
Group |
Dosage (/kg) |
n |
Death toll in 7 days |
Be subjected to the reagent thing |
3.00g |
10 |
8 |
Be subjected to the reagent thing |
1.50g |
10 |
10 |
Be subjected to the reagent thing |
0.75g |
10 |
10 |
Norfloxacin |
600mg |
10 |
1* |
Ordinary water |
20ml |
10 |
9 |
As seen the result is subjected in 7 days of three dosage groups of reagent thing death toll close with the ordinary water group, the difference nonsignificance.Prompting this product does not have obvious protective effect to the coli-infection mice.
11. resistance to deformation bacillus infection test in the body
Get 50 of mices, body weight 21~25g, ♀ ♂ half and half, divide 5 groups and ig administration at random: three groups are given and are subjected to reagent thing crude drug dried cream powder, and positive controls is given TMP+SMZ, and the blank group is given ordinary water, and the administration volume is 20ml/kg, and dosage sees Table 11.Promptly do microbiological contamination in the body after the administration: every Mus ip 3 * 10
8The Bacillus proteus of CFU/ml (bacterium number 49102, contain 2% dry yeast) bacterium liquid 23ml/kg.Commensurability again administration is 1 time after 5 hours.Death toll and the death time in 7 days after the mice microbiological contamination respectively organized in record, with the ordinary water group relatively, do to simplify exact propability and t value method is analyzed.The results are shown in Table 11.
Resistance to deformation bacillus infection result of the test in table 11 body
Group |
Dosage (/kg) |
n |
Death toll in 7 days |
Be subjected to the reagent thing |
3.00g |
10 |
6 |
Be subjected to the reagent thing |
1.50g |
10 |
8 |
Be subjected to the reagent thing |
0.75g |
10 |
9 |
TMP+SMZ |
768mg |
10 |
0
** |
Ordinary water |
20ml |
10 |
9 |
As seen the result is subjected to death toll and the equal nonsignificance of ordinary water group difference in 7 days of three dosage of reagent thing, but the death toll of heavy dose of group reduces 33.3% than ordinary water group.Seemingly point out this product that the Bacillus proteus infecting mouse is had certain protection effect trend.
12. in-vitro antibacterial test (doubling dilution)
To be subjected to reagent thing crude drug dried cream powder to do serial two-fold dilution respectively with each fluid medium, make the serial pastille culture medium of variable concentrations, packing sterilization small test tube, every pipe 1ml.Each confession examination bacterium liquid (10 with prepared fresh
5CFU/ml) 0.1ml is inoculated in respectively in the corresponding serial pastille culture medium, and other establishes negative and positive control pipe, puts 36 ± 1 ℃ and cultivates 24h.Get respectively manage culture respectively streak inoculation cultivate 24h by above-mentioned condition again in accordingly not on the pastille solid medium, observe and have or not bacterial growth.The highest drug dilution degree that is no more than 5 with clump count the results are shown in Table 12 as the minimal inhibitory concentration (MIC) of this medicine.
Table 12 in-vitro antibacterial result of the test
Strain |
Bacterium number |
MIC (crude drug g/L) |
Escherichia coli |
CMCC(B)44102 |
60.1 |
Paracolon |
Clinical strain |
60.1 |
Bacillus proteus |
CMCC(B)49102 |
15.0 |
Staphylococcus aureus |
CMCC(B)26003 |
60.1 |
Bacillus pyocyaneus |
CMCC(B)10104 |
60.1 |
As seen the result adopts the liquid tube doubling dilution to do the in-vitro antibacterial test, is subjected to the reagent thing that escherichia coli, paracolon, staphylococcus aureus, bacillus pyocyaneus are all had certain antibacterial action, and Bacillus proteus is had tangible antibacterial action.
Conclusion:
To sum up result of the test shows, be subjected to reagent thing crude drug dried cream powder when highly concentrated solution, the human body lithangiuria to be had certain litholytic effect, escherichia coli, paracolon, staphylococcus aureus, bacillus pyocyaneus all there are certain antibacterial action, Bacillus proteus is had tangible antibacterial action; With its solution and pastille serum thereof, urine guinea pig in vitro smooth muscle of bladder tension force is not all had obvious influence, also can not the antagonism acetylcholine to the excitation of smooth muscle of bladder.Being subjected to reagent thing crude drug dried cream powder solution gastric infusion, ethylene glycol being brought out kidney of rats calculus and foreign body bring out the rat bladder calculus certain inhibitory action is all arranged; The mice hot plate is caused pain certain analgesic activity, but Dichlorodiphenyl Acetate induced mice stomachache does not have obviously influence; Rat paw edema all has certain inhibitory action due to Dichlorodiphenyl Acetate induced mice peritoneum inflammatory exudation and the carrageenin; The effect that increases the rat urine amount is arranged; The Bacillus proteus infecting mouse seemingly there is certain protection effect trend, but the coli-infection mice is not had obvious protective effect.More than effect provides certain animal experiment foundation for the clinical practice of this product.
The clinical trial of this pharmaceutical composition:
Better through clinical trial proof curative effect, total effective rate 93.25%, wherein: produce effects 59.2%, effective 34.1%, clinical experiment result such as following table:
Therapeutic scheme: pill of the present invention for oral administration merely, each 5, every day 3 times, acute urinary system infection person, 7 days is a course of treatment, chronic urinary system infection, urinary calculus, 28 days is a course of treatment.
Criterion of therapeutical effect:
(1) produce effects
1, urinary calculus person, calculus is discharged, or the calculus shadow disappears, or obviously dwindles, or calculus obviously descends, and clinical symptoms is eliminated, and hydronephrosis is eliminated, and routine urinalysis is normal.
2, urinary system infection person, clinical symptoms and sign are eliminated, the cloudy commentaries on classics of the every positivity index of relevant laboratory.
(2) effective
1, urinary calculus person does not reach the produce effects standard, but clinical symptom disappearance or alleviate.
2, urinary system infection person, clinical symptoms and sign are improved, and the relevant every positivity index of laboratory is not cloudy fully to be changeed.
(3) invalid
The calculus no change, clinical symptoms, sign, the relevant every positivity index of laboratory does not have improvement.
Chinese medicine preparation of the present invention has infection, antiinflammatory, spasmolytic, diuresis, Sal Nitri, calculus effect easily, can eliminate clinical symptoms quickly, and is evident in efficacy.