CN1927375A - Traditional Chinese medicine preparation for heat-clearing, dampness-removing, diuresis and stone removing and its preparation - Google Patents

Abstract

The invention relates to a traditional Chinese preparation for reducing fever and removing dampness, as well as process for preparation, wherein the medicament is prepared from raw materials including red phaseolus bean, Chinese angelica root, climbing fern spore, lysimachia christinae, chicken's gizzard-skin, cattail pollen, achyranthes and cyathula root, curcuma aromatica, and amber.

Description

A kind of clearing away heat-damp and promoting diuresis, the Chinese medicine preparation for the treatment of stranguria and eliminating stone and preparation thereof

Technical field:

The present invention relates to a kind of clearing away heat-damp and promoting diuresis, the Chinese medicine preparation for the treatment of stranguria and eliminating stone and preparation thereof, the particularly Chinese medicine preparation made from Chinese medicine Semen Phaseoli, Radix Angelicae Sinensis, Spora Lygodii, Herba Lysimachiae, Endothelium Corneum Gigeriae Galli, Pollen Typhae, Radix Achyranthis Bidentatae, Radix Curcumae, succinum etc.

Background technology:

Urinary system calculus and cholelithiasis are common clinical, and existing main treatment means is: surgical operation, medicine calculus, naturopathy etc.In Drug therapy, it important effect Chinese medicine, in recent years, along with going deep into of clinical research, the Chinese medicine preparation that also occurs some treatment urinary system calculus and cholelithiasis on the market, cure the symptoms, not the disease but existing medicine belongs to a bit, some uses expensive composition, and some interrupts use because uncertain therapeutic efficacy is cut in application process.In view of this, the inventor develop a kind of taking convenience, effect steadily, determined curative effect, dosage form is stable, quality controllable and the treatment urinary system calculus that has no side effect and the pure Chinese medicinal preparation of cholelithiasis, to satisfy the demand of extensive patients.

Chinese medicine preparation of the present invention is pure compound Chinese medicinal preparation, thinks clearing away heat-damp and promoting diuresis, treating stranguria and eliminating stone, and the depressed liver-energy dispersing and function of gallbladder promoting calculus is in harmony then, has promptly remedied the deficiency of Western medicine, obtains satisfied curative effect again.

Summary of the invention:

The invention provides a kind of Chinese medicine preparation for the treatment of urinary system calculus and cholelithiasis, said preparation is made up of pharmaceutically active substance and medicine acceptable carrier, and wherein said pharmaceutically active substance is made by following Chinese medicine raw materials by weight proportion:

Semen Phaseoli 210～840g Radix Angelicae Sinensis 84～336g succinum 21～84g

Spora Lygodii 84～336g Herba Lysimachiae 420～1680g Endothelium Corneum Gigeriae Galli 70～280g

Pollen Typhae 70～280g Radix Achyranthis Bidentatae 105～420g Radix Curcumae 84～336g

Most preferred consisting of:

Semen Phaseoli 420g Radix Angelicae Sinensis 168g succinum 42g

Spora Lygodii 168g Herba Lysimachiae 840g Endothelium Corneum Gigeriae Galli 140g

Pollen Typhae 140g Radix Achyranthis Bidentatae 210g Radix Curcumae 168g

Or

Semen Phaseoli 840g Radix Angelicae Sinensis 336g succinum 84g

Spora Lygodii 336g Herba Lysimachiae 1680g Endothelium Corneum Gigeriae Galli 280g

Pollen Typhae 280g Radix Achyranthis Bidentatae 420g Radix Curcumae 336g

In more than forming, the weight of each medicine of distinguishing the flavor of is calculated with crude drug, and above-mentioned prescription composition can be made into 1000 doses of pharmaceutical preparatioies.The described dose of final drug preparation that finger is made refers to 1000 of capsule preparations for 1000 doses as capsule, and tablet refers to 1000 in tablet for 1000 doses, is granule 1000 grams for granule, and oral liquid is oral liquid 1000ml etc.

More than form to be by weight as proportioning, when producing, can increase or reduce according to corresponding proportion, as large-scale production can be unit with the kilogram, or be unit with the ton, small-scale production can be unit with the milligram also, weight can increase or reduce, but the constant rate of the raw medicinal herbs weight proportion between each composition.

The ratio of above weight proportion obtains through science screening, for especial patient, and as serious symptom or light disease, fat or modest patient, the proportioning of the amount of can corresponding adjustment forming increases or reduces being no more than 100%, and drug effect is constant.

Raw material of Chinese medicine, especially adjuvant drug in more than forming can be replaced with the suitable Chinese medicine with identical property of medicine with messenger drug, and its drug effect of the Chinese medicine preparation after the replacement is constant.

Chinese medicine preparation of the present invention is to process through extraction or other modes by the raw material of Chinese medicine that above-mentioned prescription is formed, and makes pharmaceutically active substance, subsequently, with this material is raw material, adds the medicine acceptable carrier when needing, and makes according to the routine techniques of galenic pharmacy.Described active substance can obtain by extracting raw material of Chinese medicine respectively, also can obtain by the co-extracted raw material of Chinese medicine, also can obtain by other modes, as: by pulverize, squeeze, calcine, grind, sieve, percolation, extraction, water are carried, alcohol extraction, ester are carried, methods such as ketone is carried, chromatography obtain, these active substances can be the material of extractum form, can be that dry extract also can be a fluid extract, make different concentration according to the different needs decision of preparation.

Pharmaceutical preparation of the present invention, preferably the pharmaceutical dosage forms of unit dose can be made any pharmaceutically useful dosage form when making pharmaceutical preparation, and these dosage forms are selected from: tablet is as conventional tablet, sugar coated tablet, film coated tablet, enteric coated tablet; Capsule is as hard capsule, soft capsule; And oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, solution, injection, suppository, ointment, plaster, cream, spray, drop, patch.

Chinese medicine preparation of the present invention is the oral formulations form preferably, most preferably granule.

Chinese medicine preparation of the present invention can add some medicine acceptable carriers as required, can adopt the galenic pharmacy routine techniques to prepare this Chinese medicine preparation, as pharmaceutically active substance is mixed with the medicine acceptable carrier.Described medicine acceptable carrier is selected from: mannitol, sorbitol, sorbic acid or potassium salt, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin A, vitamin C, vitamin E, vitamin D, azone, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, alginate, gelatin, polyvinylpyrrolidone, glycerol, propylene glycol, ethanol, soil temperature 60-80, span-80, Cera Flava, lanoline, liquid paraffin, hexadecanol, gallate ester, agar, triethanolamine, basic amino acid, carbamide, allantoin, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, the phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.

Chinese medicine preparation of the present invention, when making medicament, the medicament of unit dose can contain pharmaceutically active substance 0.1-1000mg of the present invention, and all the other are pharmaceutically acceptable carrier.Pharmaceutically acceptable carrier can be the 0.1-99.9% of total formulation weight amount by weight.

Pharmaceutical preparation of the present invention, its pharmaceutically active substance makes through extracting processing, and processing can be adopted any combination in the said method, but most preferred method of the present invention is as follows:

[method for making] above nine flavors, Succinum powder is broken into fine powder, eight flavors such as all the other Semen Phaseolis decoct with water 1-3 time, each 1-3 hour, collecting decoction filtered, filtrate is condensed into thick paste (relative density 1.20～1.40) or filtrate is concentrated into clear paste (relative density 1.08～1.12), add 80% ethanol of 1～1.2 times of amount, staticly settled 24～48 hours, get supernatant recovery ethanol and be condensed into thick paste (relative density 1.20～1.40).Get above-mentioned thick paste, add the succinum fine powder and promptly get pharmaceutically active substance of the present invention.This method is that the present invention obtains through screening.

Its function of Chinese medicine preparation of the present invention with cure mainly into:

1, clearing away heat-damp and promoting diuresis, treating stranguria and eliminating stone.Be used for stranguria caused by urinary stone, stranguria with blood, urinary system calculus and belong to damp and hot stasis of blood knot card person.(treatment urinary system calculus)

2, clearing away heat-damp and promoting diuresis, the depressed liver-energy dispersing and function of gallbladder promoting calculus.Cure mainly: cholelithiasis dampness-heat in the liver and gallbladder, QI and blood stasis card.(treatment cholelithiasis)

The most preferred prescription of the present invention is listed in the embodiment of the invention.

Following data declaration beneficial effect of the present invention by experiment.

The succinum Sal Nitri granule Pharmacodynamic test of active extract relevant with cholelithiasis

1 test material

1.1 be subjected to the reagent thing

Nomenclature of drug: use the extractum of the method preparation of the embodiment of the invention 1, be called succinum Sal Nitri granule in the experiment

The unit of providing: Shandong China Wo Medicine Co

Form: Semen Phaseoli, Radix Angelicae Sinensis, Spora Lygodii, Herba Lysimachiae, Endothelium Corneum Gigeriae Galli, Pollen Typhae, Radix Achyranthis Bidentatae, Radix Curcumae, succinum

Dosage: determine that the high, medium and low dosage group of rat crude drug amount is respectively 40g/kg, 20g/kg, 10g/kg, extractum becomes to contain crude drug concentration with distilled water diluting and is respectively 400%, 200%, 100% during administration, and the administration volume is 1ml/100g; Rabbit duodenal administration lot number is 20030116, and administration crude drug concentration is respectively 1000%, 500%, 250%, and the administration volume is 2ml/kg,

1.2 contrast medicine

The cholagogic and lithagogue granule, Fu Dong pharmaceutical Co. Ltd in Shenyang produces, lot number: 000358, clothes dosage was that 12g becomes desired concn with distilled water diluting in clinical day.Rat oral gavage concentration 17%, rabbit duodenal administration concentration are 40%, are all, and the administration volume is respectively 1ml/100g, 2ml/kg, and dosage is equivalent to 10 times, 5 times of clinical people's consumption per day respectively.

1.3 reagent

Acecoline, reagent three factories in Shanghai produce, lot number: 971218

Histamine phosphate, the beautiful pearl east wind in Shanghai Bioisystech Co., Ltd produces, lot number 9904060

Pentobarbital sodium, China Medicine (Group) Shanghai Chemical Reagent Co., produces, lot number: 971104

Ethylurethanm, China Medicine (Group) Shanghai Chemical Reagent Co., produces, lot number: 2002423

1.4 experimental animal

The Wistar rat is provided by Shandong University's animal center, the animal quality certification number: 20021024;

New zealand rabbit is provided by Shandong Traditional Chinese Medicine University animal experiment chamber, the animal quality certification number: 20030004;

Cavia porcellus is provided by Shandong Traditional Chinese Medicine University animal experiment chamber, the animal quality certification number: 20030002

1.5 test equipment

Instrument BL-310 biological function pilot system, Tai Meng company in Chengdu makes

R-200D1/ ten thousand electronic balances: Shanghai balance equipment factory.

Conventional laparotomy ventrotomy apparatus one cover of animal etc.

2 test methods and result

2.1 succinum Sal Nitri granule rat acute function of gallbladder promoting test

100 of healthy male Wistar rats, body weight 250 ± 50g is divided into 5 groups at random, normal saline group, the large, medium and small dosage group of succinum Sal Nitri granule, cholagogic and lithagogue granule matched group, 20 every group.Water 12h is can't help in the animal fasting before the test.After every animal lumbar injection urethane (1g/kg) is anaesthetized during test.Back of the body position is fixed, and 3cm opens abdomen in the place under xiphoid-process, seeks by duodenum and sees common bile duct, separates one section bile duct, and the nearly duodenum end of threading ligation is made V-notch on bile duct, inserts 7 number sword-shaped needles and draws the bile outflow, uses cup collection bile in a small amount.The fixing head sword-shaped needle, folder closes the abdominal cavity, and covers with the gauze that dips in normal saline.After stablizing 15min, collect the bile excretion figureofmerit of 30min bile before as administration.Then from the duodenum respectively large, medium and small dosage of administration, positive control drug and normal saline, collect 0 ~ 30min after the administration respectively, 30 ~ 60min, 60 ~ 90min, and bile flow in 90 ~ 120min.Result of the test sees Table 1:

Table 1: succinum Sal Nitri granule is to the influence of rat bile flow (unit: the ml of X ± SD)

Group	Before the medicine	Administration 30min	60min	90min	120min
						The heavy dose of group of dosage group cholagogic and lithagogue granule in the normal saline group small dose group	0.19±0.07 0.18±0.07 0.17±0.05 0.19±0.08 0.19±0.08	0.18±0.08 0.20±0.08 0.24±0.13 0.27±0.09 Δ 0.22±0.09	0.20±0.08 0.24±0.07 Δ 0.24±0.10 Δ 0.30±0.10 ΔΔ※ 0.23±0.09	0.19±0.09 0.25±0.07 0.28±0.10 ΔΔ 0.30±0.10 ΔΔ 0.27±0.07 Δ	0.19±0.11 0.24±0.08 0.25±0.09 Δ 0.26±0.07 Δ 0.23±0.07

Compare Δ P＜0.05 with the normal saline group, Δ Δ P＜0.01 is with cholagogic and lithagogue granule ※ P＜0.05

From test as can be seen: succinum Sal Nitri granule has more short bile excretion effect, and different time sections and normal saline group relatively obviously increase with dosage increasing bile excretion amount behind the medicine.30min should act at once and occurring after heavy dose was taken medicine, and low dose of, middle dosage relatively has significant difference at 60min and normal saline group, and secretion peak can be kept about 2h about 90min.This effect is better than cholagogic and lithagogue granule (P＜0.05).

2.2 succinum Sal Nitri granule is to the bioelectric influence of rabbit sphincter muscle of bile duct

40 of rabbit are divided into 5 groups at random, and 8 every group, 12h fasting before the test.Auricular vein is injected 0.5% pentobarbital sodium (4ml/kg) anesthesia, facing upward the position is fixed on the rabbit dissecting table, the epigastrium cropping, cut the about 6-8cm of skin from xiphoid-process hypogastric region median line, along center hunter's line open abdomen, as seen the duodenum that finds stomachus pyloricus and link to each other is opened on duodenal common bile duct ampulla, and can tracks common bile duct to the upper right side.A pair of with 20mm enamel-covered wire copper wire electrode, one is placed on common bile duct, and one is placed on the common bile duct ampulla, and two are passed about placenta percreta 0.3cm at a distance of 0.3cm, curves the back fixed electrode, and indifferent electrode places abdominal incision subcutaneous.Regulate test parameters, observe earlier normal myoelectricity frequency before the administration (inferior/min) and amplitude (μ v), duodenal administration then: 1. normal saline 1ml/kg, 2.～4. succinum Sal Nitri granule, 5. cholagogic and lithagogue granule.Observe 30min, 60min behind the medicine, the bioelectric frequency of 90min and amplitude, table 2, table 3 as a result then:

Table 2: succinum Sal Nitri granule to the influence of the normal sphincter muscle of bile duct bio electricity of rabbit frequency (X ± SD) (inferior/min)

Group	Before the medicine	30min	60min	90min
					The heavy dose of cholagogic and lithagogue granule of dosage in the NS low dose	336±55 336±81 354±95 318±54 330±67	324±61 324±55 420±111 414±102 Δ 306±73	342±42 288±36 492±110 Δ 474±109 ΔΔ 342±97	306±50 324±48 300±47 312±65 300±76

Compare Δ P＜0.05, Δ Δ P＜0.01 with the normal saline group

Table 3: succinum Sal Nitri granule is to the influence of the normal sphincter muscle of bile duct bio electricity of the rabbit amplitude (unit of X ± SD): μ v

Group	Before the medicine	30min	60min	90min
					The heavy dose of cholagogic and lithagogue granule of dosage in the NS low dose	69.0±32.9 76.8±28.0 60.8±13.1 68.1±10.1 23.4±3.60	89.3±37.4 118.7±36.5 Δ 219.6±66.6 ΔΔ 294.1±124.7 ΔΔ 204.2±62.7 ΔΔ	77.7±37.0 171.8±50.8 ΔΔ 275.5±58.4 ΔΔ 462.1±127.6 ΔΔ 260.9±145.8 ΔΔ	74.8±38.0 138.5±31.1 ΔΔ 216.2±47.7 ΔΔ 326.1±104.8 ΔΔ 169.9±68.6 ΔΔ

Compare Δ P＜0.05, Δ Δ P＜0.01 with the normal saline group

By test as can be seen, succinum Sal Nitri granule increases the bio electricity frequency of rabbit sphincter muscle of bile duct, middle dosage relatively has significant difference at 60min and normal saline group, heavy dose of relatively have significant difference (P＜0.05 at 30min, 60min and normal saline group, p＜0.01), unknown significance difference in other dosage and time period; But comparatively obvious to the voltage amplitude influence, compare with the normal saline group, 30min can keep about about 2h in onset.

2.3 the influence that succinum Sal Nitri granule shrinks the gallbladder that exsomatizes

Get 20 of Cavia porcelluss, male and female are regardless of, and body weight 250 ± 50g takes out gallbladder immediately after the sacrificed by decapitation, and cuts an osculum in the bottom, washes down bile with nutritional solution, and preparation gallbladder sphincter specimen is done the sphincteral shrinkage test of gallbladder in filling the surface plate of krebs solution.Distinguish anchor line (string) at the gallbladder bottom sphincter mouth of pipe during test, vertically hang, each specimen adjustment load, make the load basically identical, do the influence of medicine earlier, after flushing is stable the contractile response of normal gallbladder, acecoline and mixtures of histamine that Maxwell isolated smooth muscle groove adds 0.5ml2% cause convulsion, add the medicine of variable concentrations after 1 minute respectively, observe its antagonism, every specimen is only made antagonistic effect one time.Containing krebs solution in the pipe of Maxwell is 40ml, and water jacket fills with krebs solution, bathes 37 ± 0.5 ℃ of temperature, and nutritional solution PH is 7.5, and passes to oxygen.First balance 10min before each test.The results are shown in Table 4, table 5, table 6, table 7.:

Table 4: succinum Sal Nitri granule to the influence of the normal contraction frequency of guinea pig in vitro gallbladder (X ± SD) (inferior/min)

Group	Before the medicine	At once	5min	10min
					The heavy dose of cholagogic and lithagogue granule of dosage in the NS low dose	14.3±3.67 13.1±4.15 13.4±3.31 14.2±3.26 14.0±4.78	12.8±3.43 14.4±4.12 15.1±3.54 14.4±3.84 13.5±2.64	13.4±3.34 16.2±3.58 14.6±3.95 15.6±4.50 14.2±3.55	14.4±3.78 13.5±3.41 14.1±4.58 14.7±3.09 14.0±2.87

With before the medicine and normal saline group comparison P＞0.05

Table 5: succinum Sal Nitri granule is to influence (X ± SD) (g) of guinea pig in vitro gallbladder normal amplitude

Group	Before the medicine	At once	5min	10min
					The heavy dose of cholagogic and lithagogue granule of dosage in the NS low dose	0.091±0.030 0.082±0.016 0.083±0.022 0.080±0.024 0.077±0.025	0.090±0.026 0.105±0.025 Δ 0.107±0.021 Δ 0.103±0.024 Δ 0.103±0.019 Δ	0.086±0.016 0.101±0.015 Δ 0.106±0.026 Δ 0.105±0.022 Δ 0.086±0.023	0.087±0.015 0.087±0.014 0.082±0.015 0.095±0.018 0.080±0.017

With comparison Δ P＜0.05 before the medicine

Table 4, table 5 result of the test show: with comparison before the medicine, succinum Sal Nitri granule is not clearly to the normal gallbladder contraction frequency influence of exsomatizing, but the increase to some extent of its amplitude (P＜0.05).

Table 6: succinum Sal Nitri granule causes the influence (X ± SD) (inferior/minute) of the contraction frequency after the convulsion to the guinea pig in vitro gallbladder

Group	Before the medicine	At once	5min	10min
					The heavy dose of cholagogic and lithagogue granule of dosage in the normal saline group low dose	19.2±5.9 20.6±8.2 22.1±3.9 21.3±5.6 20.6±7.5	17.5±3.9 14.8±5.4 17.2±4.4 Δ 14.7±4.7 Δ 15.0±3.7	15.5±3.0 16.4±4.4 18.0±2.5 Δ 15.5±5.7 Δ 18.7±4.2	15.2±3.2 18.5±5.2 19.2±5.6 17.2±4.9 16.4±5.3

Compare Δ P＜0.05 with the normal saline group

Table 7: succinum Sal Nitri granule causes influence (X ± SD) (g) of convulsion backward pull to the guinea pig in vitro gallbladder

Group	Before the medicine	At once	5min	10min
					The heavy dose of cholagogic and lithagogue granule of dosage in the normal saline group low dose	1.50±0.22 1.46±0.38 1.59±0.19 1.63±0.25 1.56±0.21	1.53±0.31 1.48±0.15 1.41±0.11 Δ 1.34±0.18 Δ 1.33±0.21 Δ	1.50±0.24 1.35±0.19 1.39±0.18 Δ 1.34±0.21 Δ 1.50±0.19	1.59±0.35 1.47±0.22 1.38±0.12 1.42±0.17 1.48±0.24

Compare Δ P＜0.05 with the normal saline group

Result of the test shows, succinum Sal Nitri granule can make the automatic shrinkage amplitude of normal sphincter muscle of bile duct increase, and frequency is accelerated not obvious, and tension force increases obviously, to the spasmolysis apparent in view (P＜0.05) of the sphincter muscle of bile duct of spasm due to the acecoline.

2.4 succinum Sal Nitri granule is to the external litholytic influence of people's cholelithiasis

Get cholelithiasis patient calculus, be divided into 5 groups at random, 10 every group by the shape size.The cholelithiasis specimen is put into 37 ℃? be dried to constant weight in the thermostatic drier, take by weighing a certain amount of cholelithiasis specimen and put into test tube with ground stopper, add the trial drug solution 10ml of distilled water or variable concentrations respectively.Measure the particulate pH value of succinum Sal Nitri, distilled water is identical with succinum Sal Nitri granule with the dilute hydrochloric acid adjust pH, and test tube is put into 37 ℃ of waters bath with thermostatic control, and every day is test tube turned upside down 2 times, and all test tubes are changed dressings once every day, and dosage is identical.7 days after-filtration take out cholelithiasis, 37 ℃ once more freeze-day with constant temperature calculate the cholelithiasis weight change to constant weight, result of the test sees Table 8:

Table 8: outer lithodialysis result of the test (X ± SD) (mg) of succinum Sal Nitri granule

Group	Before the medicine	Behind the medicine	Alleviate percentage rate
				Normal saline group small dose group	47.59±7.87 49.62±8.65	44.54±7.14 41.75±7.23 Δ	6.4 15.9

The heavy dose of group of middle dosage group cholagogic and lithagogue granule

48.67±6.75 48.51±8.13 48.42±8.36

24.06±7.16 ΔΔ 15.84±3.81 ΔΔ 29.14±8.45 Δ

50.6 67.3 39.8

With comparison Δ P＜0.05 before the medicine, Δ Δ P＜0.01,

Result of the test shows: succinum Sal Nitri granule small dose group just has good in-vitro litholytic effect (P＜0.05), and middle dosage and heavy dose have utmost point remarkable vitro litholytic effect (P＜0.01), than the cholagogic and lithagogue granule positive effect (P＜0.05) is arranged.

2.5 succinum Sal Nitri granule is to cholelithiasis litholytic influence in the rabbit body

40 of rabbit are divided into 5 groups at random, and 8 every group, 12h fasting before the test.Inject 0.5% pentobarbital sodium (4ml/kg) anesthesia from auricular vein, facing upward the position is fixed on the rabbit dissecting table, the epigastrium cropping, the skin routine disinfection, cut the about 6-8cm of skin with the sterile working from xiphoid-process hypogastric region median line,, find gallbladder along center hunter's line open abdomen, take people's cholelithiasis that uviol lamp is sterilized and is dried to constant weight, weight is about 15mg, is embedded in the gallbladder of rabbit, and cholelithiasis is fixed, every rabbit intramuscular injection gentamycin 0.5ml, for three days on end, and from the 3rd day the beginning, rabbit is irritated the stomach normal saline respectively, succinum Sal Nitri granule low dose, dosage in the succinum Sal Nitri granule, succinum Sal Nitri granule heavy dose and cholagogic and lithagogue granule, the administration volume is 5ml/kg, successive administration 21 days, the 22nd day with all sacrifice of animal dissections, ligation cystic duct, take out gallbladder, get the cholelithiasis weighing that dries to constant weight.Gallbladder is with 10% formaldehyde fixed, and conventional embedded section is observed the pathological change influence to gallbladder, and result of the test sees Table 9,10 and attached photo:

Table 9: succinum Sal Nitri granule is to lithodialysis result (X ± SD) (mg) of cholelithiasis in the rabbit body

Group	Before the medicine	Behind the medicine	Alleviate percentage rate
				The heavy dose of cholagogic and lithagogue granule of dosage in the normal saline group low dose	24.5±5.3 24.0±3.8 25.1±5.6 25.1±5.4 26.2±6.2	21.2±3.3 20.1±4.2 Δ 17.0±8.9 ΔΔ 9.6±8.5 ΔΔ 16.4±9.0 ΔΔ	13.5 16.3 32.3 61.8 37

With comparison Δ P＜0.05 before the medicine, Δ Δ P＜0.014

Result of the test shows: succinum Sal Nitri granule can promote people's cholelithiasis in the intravital dissolving of rabbit, low dose of calculus alleviates percentage rate and reaches 16.3%, heavy dose alleviates rate can reach 61.8%, relatively has significant difference with the normal saline group, with the increase litholytic effect enhancing of dosage.

Table 10: succinum Sal Nitri granule is to the pathology effects result of cholelithiasis rabbit gallbladder

Group	Pathological examination
		The heavy dose of group of dosage group cholagogic and lithagogue granule in the normal saline group small dose group	Gallbladder mucosa comes off, and ulcer is arranged, and a large amount of inflammatory cells exist.Ulcer is arranged individually, a large amount of chronic inflammation cellular infiltrations are arranged under mucous layer and the mucosa, vasodilation, edema under the mucosa.A small amount of chronic inflammation cellular infiltration is arranged, the slight hypertrophy of mucosa body of gland, degree circle is between low dose and heavy dose.The cell infiltration that minute quantity is arranged under the mucosa is not seen ulcer, hypertrophy, edema.Similar to middle dosage

Conclusion:

Succinum Sal Nitri granule can obviously promote biliary drainage; The bio electricity of rabbit sphincter muscle of bile duct be can increase, its frequency and amplitude increased; Isolated test shows, succinum Sal Nitri granule can make the automatic shrinkage amplitude of normal sphincter muscle of bile duct increase, but it is not obvious that it increases frequency change, apparent in view to the spasmolysis of the sphincter muscle of bile duct of spasm due to histamine, the acetylcholine, obviously reduces contraction frequency and shrinkage amplitude; The dissolving of the inside and outside calculus of body be can promote, the dissolving and the drainage of calculus helped..From test as can be seen: succinum Sal Nitri granule has therapeutical effect to cholelithiasis.

Diuresis:

Get 24 of male rats (200-220g), be divided into 4 groups at random, 1h before the administration, each Mus is pressed the normal saline lumbar injection of 3ml/100g, and extruding rat hypogastric region, make the bladder emptying, the administration group is given 2ml/100g, the succinum Sal Nitri granule extractum (2g/ml) of 4ml/100g, and the normal control group is given the 2ml/100g normal saline and is irritated stomach, positive controls is given hydrochlorothiazide (2.5% solution) 2ml/100g, immediately rat is put into metabolic cage.Collect the urine amount totally 3 times of each treated animal after 60 minutes, each 60min.Relatively, the results are shown in Table 11 between each average of organizing the urine amount in the corresponding time organized.

Different time urine quantitative changeization relatively after table 11. was respectively organized administration

Group	Number of animals	Different time urine amount (ml/60min) after the administration
					60-120	121-180	181-240
		Succinum Sal Nitri group 2ml/100g 4ml/100g	6 6	6.2 7.4				4.0 4.8	3.6* 3.9*
Matched group	6				0.9	2.0	1.8

The hydrochlorothiazide group

6

7.8

4.6

4.2*

* compare P＜0.05 with matched group

The result confirms that the hydrochlorothiazide group has tangible diuresis, and two dosage groups of succinum Sal Nitri granule also have effect same, with matched group significant difference are arranged relatively.Its diuresis is the strongest medication one hour, and two or three hours closely equal.

2, to the effect of intestine in vitro

Get 10 of rabbit, shoot dead, get one section in 2-3cm small intestinal, put and separate mesentery in the tyrode's solution, the flushing intestinal contents, put in the tyrode's solution of 38 ℃ of saturated oxygens, an end is fixed in the maxwell bath ware, and the other end links to each other with transducer, and look instrument with physiology salt and write down its active situation automatically by many, after treating movable stablizing, give the succinum Sal Nitri granule extractum of various dose respectively, write down its enterokinesia situation.

Experimental result shows: activity has inhibitory action to succinum Sal Nitri granule to the isolated rabbit intestinal tube, and intestinal tension force is weakened, and contraction frequency is slack-off, and its action intensity improves with concentration and strengthens.

3, to the effect of white mice enterokinesia:

Get white mice (20-22g), 64, be divided into 4 groups at random, gastric infusion, the administration group is given 0.2ml/10g, 0.4ml/10g succinum Sal Nitri granule extractum (2g/ml), the normal control group is given distilled water 0.2ml/10g, positive controls is given morphine hydrochloride 0.2ml/10g (0.1%) solution, irritate after 20 minutes with the active carbon rubber cement, put to death after 20 minutes again, cut open the belly and measure the distance that pylorus to active carbon advances the forward position, the results are shown in Table 12.

Table 12. succinum Sal Nitri granule is to the influence of mouse small intestine ahead running

Group	Number of animals	Dosage	Active carbon propelling branch rate (%) (X ± SD)
				Succinum Sal Nitri group	16	0.2ml/10g	?24.3±4.0*
16	0.4ml/10g	?22.8±4.5*
			The morphine hydrochloride group		16	0.2ml/10g	?22.9±4.3*
Matched group	16	0.2ml/10g		?51.5±5.6

* compare p＜0.05 with matched group

Experimental result shows: morphine hydrochloride is the intestinal propulsion movement slows down, succinum Sal Nitri granule has also delayed the propelling of active carbon in the white mice intestinal, active carbon propelling rate and matched group more all have significant difference, illustrate that succinum Sal Nitri granule has inhibitory action to enterokinesia.Medication group active carbon holdup time in small intestinal prolongs relatively, and this weakens with the intestine in vitro activity is consistent.

4, to the influence of rabbit ureter action potential

Get 24 of rabbit, body weight 2.2-2.5kg, fasting be can't help water 12 hours, pentobarbital sodium anesthesia is fixed on the rabbit dissecting table, isolates the descending ureter in left side, with two silver wire electrodes, at a distance of 0.5cm, pass the tip of upset electrode behind the about 3mm of ureter surface serous coat, and with electrode outward plastic tube touch downwards and encase the upset electrode.The other end of two electrodes is connected in polygraph preamplifier input respectively.Regulate the polygraph amplifying parameters, time constant 0.02s.Filtering 1000HZ, sensitivity 10mm/mv, auricular vein successively inject normal saline 2ml/kg and succinum Sal Nitri granule extractum 2ml/kg (crude drug 2g/ml) whenever gives a kind of medicine, all writes down before the administration and different time action potential variation after the administration.

Experimental result shows that succinum Sal Nitri granule can obviously increase rabbit ureter action potential frequency, increases ureteral wriggling, keeps the long period.

5, to the effect of people's urinary stone

People's urinary stone of weighing is put in the succinum Sal Nitri granule of variable concentrations in 37 ℃, soaked 4 hours, and regularly change calculus, then calculus is taken out drying and weigh.The weight change of calculus before and after the comparative experiments.The results are shown in Table 13

Table 13. variable concentrations succinum Sal Nitri granule is to the influence of calculus weight change

Drug level (g/ml)	Calculus heavy (mg) before soaking	Soak back calculus heavy (mg)	Calculus reduction and percentage rate
					Mg	％
			1	158.7			144.9	13.8	8.7
2	183.1	170.1			13.1	7.2
			3	150.4			141.3	9.1	6.1
4	164.8	148.6			16.2	9.8
			5	90.7			79.1	11.6	12.8
8	134.2	122.5			17.7	13.2
			0	213.3			195.7	27.6	13.0

Experimental result shows that the succinum Sal Nitri granule of variable concentrations compares not statistically significant to the dissolution of people's urinary stone with distilled water, does not have tangible dissolution.

6, acute toxicity test

Hold 1.0ml (crude drug 4.5g/ml) with maximum stomach for white mice (18-22g) with succinum Sal Nitri granule extractum, 20 in two batches, observe and do not see mice dying and abnormal phenomena in 72 hours, continue to observe 14 days also no abnormality seens, be that the 225g/kg body weight is irritated stomach for its dosis tolerata, be equivalent to 188 times of clinical application amounts.

Showing that this poison of drug is low, is safe to the people.

7, long term toxication

Get 80 of healthy rats (180-210g), be divided into four groups, every group of male and female half and half, totally 20, wherein 3 groups give succinum Sal Nitri extractum respectively, with 225g/kg, 75g/kg, the dosage of 22.5g/kg is sneaked in the bait, and another is organized with common diet feeding.Raising rat writes down one time appetite 90 day every day under all identical situation of other raising condition.Body weight change of per five days records.After the last administration 24 hours, put to death 13 animals for every group, to get stomach, liver, kidney and do pathologic finding and chemically examine its routine blood test, routine urinalysis stays 7 animal drug withdrawals and observed for 4 weeks, puts to death and checks.

Experimental result shows, appetite changes also there was no significant difference of no evident regularity between four experimental grouies, body weight all increases to some extent, in 90 days, four groups of body weight increase by 74.7%, 81.0%, 81.6%, 80.8% respectively, there was no significant difference, back 4 all weight increase are there was no significant difference also, and check pathological section and hematuria routine test be no abnormality seen also.

Brief summary: experimental result shows, succinum Sal Nitri granule has tangible diuresis, intestinal smooth muscle there is inhibitory action, reduced its irritability, make level and smooth hypomyotonia, and increase ureter action potential frequency, accelerate ureteral wriggling, be beneficial to calculus and discharge, above-mentioned may be one of calculus reason of discharging.The succinum Sal Nitri granule of multiple variable concentrations is not seen its toxic reaction in whole experiment, do not find reversible toxicity and retardance toxicity yet, is a kind of medicine of diuresis and expelling stone safely and effectively.

Prescription of the present invention and method for making obtain through screening, and particularly most preferred prescription and method for making have solved operating difficulties in the process for preparation, make product more stable, are difficult for the moisture absorption, long shelf-life, and biological utilisation improves.

The specific embodiment:

Further specify the present invention by the following examples, but not as limitation of the present invention.

Embodiment 1

Semen Phaseoli 840g Radix Angelicae Sinensis 336g succinum 84g

Spora Lygodii 336g Herba Lysimachiae 1680g Endothelium Corneum Gigeriae Galli 280g

Pollen Typhae 280g Radix Achyranthis Bidentatae 420g Radix Curcumae 336g

[method for making] above nine flavors, Succinum powder is broken into fine powder, eight flavors such as all the other Semen Phaseolis decoct with water secondary, each 1.5 hours, collecting decoction filtered, filtrate is condensed into thick paste (relative density 1.20～1.40) or filtrate is concentrated into clear paste (relative density 1.08～1.12), add 80% ethanol of 1 times of amount, staticly settled 24 hours, get supernatant recovery ethanol and be condensed into thick paste (relative density 1.20～1.40).Get above-mentioned thick paste, add the succinum fine powder and obtain pharmaceutically active substance of the present invention, add an amount of dextrin, make granule, drying is made 1000g, promptly.

Embodiment 2

Semen Phaseoli 210g Radix Angelicae Sinensis 84g succinum 21g

Spora Lygodii 84g Herba Lysimachiae 420g Endothelium Corneum Gigeriae Galli 70g

Pollen Typhae 70g Radix Achyranthis Bidentatae 105g Radix Curcumae 84g

[method for making] above nine flavors, Succinum powder is broken into fine powder, eight flavors such as all the other Semen Phaseolis decoct with water secondary, each 1.5 hours, collecting decoction filtered, filtrate is condensed into thick paste (relative density 1.20～1.40) or filtrate is concentrated into clear paste (relative density 1.08～1.12), add 80% ethanol of 1.2 times of amounts, staticly settled 48 hours, get supernatant recovery ethanol and be condensed into thick paste (relative density 1.20～1.40).Get above-mentioned thick paste, add the succinum fine powder and obtain pharmaceutically active substance of the present invention, add an amount of dextrin, make granule, drying is made 1000g, promptly.

Embodiment 3

Semen Phaseoli 630g Radix Angelicae Sinensis 252g succinum 63g

Spora Lygodii 252g Herba Lysimachiae 1260g Endothelium Corneum Gigeriae Galli 210g

Pollen Typhae 210g Radix Achyranthis Bidentatae 315g Radix Curcumae 252g

[method for making] above nine flavors, Succinum powder is broken into fine powder, eight flavors such as all the other Semen Phaseolis decoct with water secondary, each 1.5 hours, collecting decoction filtered, filtrate is condensed into thick paste (relative density 1.20～1.40) or filtrate is concentrated into clear paste (relative density 1.08～1.12), add 80% ethanol of 1 times of amount, staticly settled 24 hours, get supernatant recovery ethanol and be condensed into thick paste (relative density 1.20～1.40).Get above-mentioned thick paste, add the succinum fine powder and obtain pharmaceutically active substance of the present invention, add an amount of dextrin, make granule, drying is made 1000g, promptly.

Embodiment 4

Semen Phaseoli 840g Radix Angelicae Sinensis 336g succinum 84g

Spora Lygodii 336g Herba Lysimachiae 1680g Endothelium Corneum Gigeriae Galli 280g

Pollen Typhae 280g Radix Achyranthis Bidentatae 420g Radix Curcumae 336g

[method for making] above nine flavors, Succinum powder is broken into fine powder, eight flavors such as all the other Semen Phaseolis decoct with water secondary, each 1.5 hours, collecting decoction filtered, filtrate is condensed into thick paste (relative density 1.20～1.40) or filtrate is concentrated into clear paste (relative density 1.08～1.12), add 80% ethanol of 1 times of amount, staticly settled 24 hours, get supernatant recovery ethanol and be condensed into thick paste (relative density 1.20～1.40).Get above-mentioned thick paste, add the succinum fine powder and obtain pharmaceutically active substance of the present invention, add an amount of dextrin, make granule, tabletting, 1000 of film-making agent.

Embodiment 5

Semen Phaseoli 840g Radix Angelicae Sinensis 336g succinum 84g

Spora Lygodii 336g Herba Lysimachiae 1680g Endothelium Corneum Gigeriae Galli 280g

Pollen Typhae 280g Radix Achyranthis Bidentatae 420g Radix Curcumae 336g

[method for making] above nine flavors, Succinum powder is broken into fine powder, eight flavors such as all the other Semen Phaseolis decoct with water secondary, each 1.5 hours, collecting decoction filtered, filtrate is condensed into thick paste (relative density 1.20～1.40) or filtrate is concentrated into clear paste (relative density 1.08～1.12), add 80% ethanol of 1.2 times of amounts, staticly settled 48 hours, get supernatant recovery ethanol and be condensed into thick paste (relative density 1.20～1.40).Get above-mentioned thick paste, add the succinum fine powder and obtain pharmaceutically active substance of the present invention, add an amount of dextrin, make granule, incapsulate 1000.

Embodiment 6

Semen Phaseoli 420g Radix Angelicae Sinensis 168g succinum 42g

Spora Lygodii 168g Herba Lysimachiae 840g Endothelium Corneum Gigeriae Galli 140g

Pollen Typhae 140g Radix Achyranthis Bidentatae 210g Radix Curcumae 168g

[method for making] above nine flavors, Succinum powder is broken into fine powder, eight flavors such as all the other Semen Phaseolis decoct with water secondary, each 1.5 hours, collecting decoction filtered, filtrate is condensed into thick paste (relative density 1.20～1.40) or filtrate is concentrated into clear paste (relative density 1.08～1.12), add 80% ethanol of 1.2 times of amounts, staticly settled 48 hours, get supernatant recovery ethanol and be condensed into thick paste (relative density 1.20～1.40).Get above-mentioned thick paste, add the succinum fine powder and obtain pharmaceutically active substance of the present invention, add an amount of dextrin and sucrose, make particle drying, make 1000g, promptly.

Claims (10)

1, a kind of Chinese medicine preparation for the treatment of urinary system calculus and cholelithiasis, said preparation is made up of pharmaceutically active substance and medicine acceptable carrier, and wherein said pharmaceutically active substance is made by following Chinese medicine raw materials by weight proportion:

Semen Phaseoli 210～840g Radix Angelicae Sinensis 84～336g succinum 21～84g

Spora Lygodii 84～336g Herba Lysimachiae 420～1680g Endothelium Corneum Gigeriae Galli 70～280g

Pollen Typhae 70～280g Radix Achyranthis Bidentatae 105～420g Radix Curcumae 84～336g

2, the Chinese medicine preparation of claim 1 is characterized in that, wherein said pharmaceutically active substance is made by following Chinese medicine raw materials by weight proportion:

Semen Phaseoli 420g Radix Angelicae Sinensis 168g succinum 42g

Spora Lygodii 168g Herba Lysimachiae 840g Endothelium Corneum Gigeriae Galli 140g

Pollen Typhae 140g Radix Achyranthis Bidentatae 210g Radix Curcumae 168g

3, the Chinese medicine preparation of claim 1 is characterized in that, wherein said pharmaceutically active substance is made by following Chinese medicine raw materials by weight proportion:

Semen Phaseoli 840g Radix Angelicae Sinensis 336g succinum 84g

Spora Lygodii 336g Herba Lysimachiae 1680g Endothelium Corneum Gigeriae Galli 280g

Pollen Typhae 280g Radix Achyranthis Bidentatae 420g Radix Curcumae 336g

4. any one Chinese medicine preparation of claim 1-3 is selected from: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, solution, injection, suppository, ointment, plaster, cream, spray, drop, patch.

5. the Chinese medicine preparation of claim 4 is granules.

6. the application of the Chinese medicine preparation of claim 1 in the medicine of preparation treatment urinary system calculus and cholelithiasis.

7, the preparation method of the Chinese medicine preparation of claim 1 is characterized in that, the process following steps:

The raw material of Chinese medicine that prescription is formed through being selected from pulverizing, squeezing, calcining, grinding, sieving, percolation, extraction, water are carried, alcohol extraction, ester are carried, ketone is carried or the step of chromatography obtains pharmaceutically active substance, with this material is raw material, add the medicine acceptable carrier when needing, make according to the routine techniques of galenic pharmacy.

8, the preparation method of claim 7 is characterized in that, the process following steps:

Succinum powder is broken into fine powder, and all the other eight flavors decoct with water each 1-3 hour 1-3 time, collecting decoction filters, and filtrate is condensed into thick paste or filtrate is concentrated into clear paste, 80% ethanol that adds 1～1.2 times of amount, staticly settled 24～48 hours, and got supernatant recovery ethanol and be condensed into thick paste, get above-mentioned thick paste, add the succinum fine powder and promptly get pharmaceutically active substance of the present invention, with this material is raw material, adds the medicine acceptable carrier when needing, and makes according to the routine techniques of galenic pharmacy.

9, the preparation method of claim 7 is characterized in that, the process following steps:

[prescription] Semen Phaseoli 420g Radix Angelicae Sinensis 168g succinum 42g

Spora Lygodii 168g Herba Lysimachiae 840g Endothelium Corneum Gigeriae Galli 140g

Pollen Typhae 140g Radix Achyranthis Bidentatae 210g Radix Curcumae 168g

[method for making] above nine flavors, Succinum powder is broken into fine powder, and eight flavors such as all the other Semen Phaseolis decoct with water secondary, and each 1.5 hours, collecting decoction filtered, and filtrate concentrates the back and adds succinum fine powder and an amount of sucrose and dextrin, makes granule, and drying is made 1000g, promptly.

10, the preparation method of claim 7 is characterized in that, the process following steps:

[prescription] Semen Phaseoli 840g Radix Angelicae Sinensis 336g succinum 84g

Spora Lygodii 336g Herba Lysimachiae 1680g Endothelium Corneum Gigeriae Galli 280g

Pollen Typhae 280g Radix Achyranthis Bidentatae 420g Radix Curcumae 336g

[method for making] above nine flavors, Succinum powder is broken into fine powder, and eight flavors such as all the other Semen Phaseolis decoct with water secondary, and each 1.5 hours, collecting decoction filtered, and filtrate concentrates the back and adds succinum fine powder and an amount of dextrin, granulates, and drying is made 1000g, promptly.