CN101549073B

CN101549073B - Medicament for treating idiopathic edema and preparation method thereof

Info

Publication number: CN101549073B
Application number: CN2008100894494A
Authority: CN
Inventors: 吴以岭; 许红辉; 李晓燕; 姬雪礼; 张永锋; 孟学强; 李向军; 郑立发; 王猛; 秦拢
Original assignee: Hebei Yiling Pharmaceutical Research Institute Co Ltd
Current assignee: Hebei Yiling Pharmaceutical Research Institute Co Ltd
Priority date: 2008-04-01
Filing date: 2008-04-01
Publication date: 2011-09-14
Anticipated expiration: 2028-04-01
Also published as: CN101549073A

Abstract

The invention provides a medicament for treating idiopathic edema and a preparation method thereof. The medicine contains pure natural plant drugs of angelica, radix bupleuri, atractylis ovata, Alismaorientale, radix paeoniae alba, tuckahoe, grifola, rhizoma cyperi, motherwort, trumpetweed, cassia twig, and the like. In the medicament, the angelica breaks extravesated blood, nourishes new blood a nd relaxes vain to eliminate dampness; radix bupleuri, tuckahoe and Alisma orientale soothes liver and strengthens spleen for inducing diuresis to alleviate edema; the atractylis ovata, grifola, and the like, invigorates qi and strengthens the spleen, clears damp and promotes diuresis and blood circulation, and recuperates the body function; the plant drugs are combined to free liver qi and strengthen the spleen, smooth collaterals, avoid moisten, and eliminate edema, so as to ensure the effect of sooth liver and strengthen spleen, smooth collaterals and induce diuresis. Research shows that the medicament has the pharmacological actions of inducing diuresis, reducing capillary permeability, improving microcirculatory disturbance and increasing immunologic function, and the like, treats idiopathic edema etiologically and semeiologically, and has the advantages and characteristics of multiple levels and treatment on principal and subordinate of traditional Chinese medicine.

Description

A kind of medicine for the treatment of idiopathic edema and preparation method thereof

Technical field

The present invention relates to a kind of medicine that is used for the treatment of idiopathic edema and preparation method thereof, belong to the Chinese herbal and crude drugs preparations technical field.

Background technology

Idiopathic edema (Idiopathic Edema) is meant that etiology unknown is one group of clinical syndrome of feature with weight increase and anasarca.Primary disease is common in the women of childbearing age, sends out the age well in 30-40 year, seldom sees before the menarche and postclimacteric women.Clinical main performance abdominal distention is characterized as the position fluid retention with non-inflammatory eyelid, face, both hands and lower limbs edema.In addition, primary disease often with the symptom of autonomic nervous dysfunctions such as anxiety, irritability, headache, also can merge dyspepsia, menoxenia, obesity and diabetes etc.Because the cause of disease and pathogenesis are not clear, still do not have medicinal application targetedly at present in clinical.

Idiopathic edema does not have corresponding definite name of disease in traditional medicine, it is close to reach " anasarca " etc. according to its symptom performance and the traditional Chinese medical science it " edema ", " general edema ".The woman is congenital with liver, blood stored in the liver, and main catharsis, property happiness bar reaches, as the catharsis malfunction, stagnation of QI due to depression of the liver, blood-vessel obstructive, menses are not smooth, mechanism of qi disorder simultaneously, the three warmers water channel is obstructed, and water liquid does not follow Chang Dao and overflows will send out in skin and be edema; " General Treatise on the Cause and Symptoms of Diseases ten water time " said: " blue or green water person, swollen all over the whole body from appearance earlier, its root is liver " illustrates that the liver failing to maintain the normal flow of QI can cause stagnation of QI water retention.Stagnation of liver-QI can cause spleen fortune not normal, the void that causes of a specified duration, through cloud: " all damp-edema completely all belong to spleen ", insufficiency of the spleen then can not transmitting and distributing the fluids, water is wet to stop in the aggressiveness and spreads unchecked and overflow so edema." Medical Treasures of the Golden Chamber " meaning: " (married woman) through be blood, menstruation disorder then is a water ", thereby its main pathomechanism is stagnation of liver-QI with deficiency of the spleen, qi depression to blood stasis, qiactivity of triple energizer is not normal.

In sum, primary disease mostly is stagnation of liver-QI with deficiency of the spleen, qi depression to blood stasis and causing, and treatment is always with soothing liver and strengthening spleen, and activating blood and promoting diuresis is main.

Compositions such as choice of drug pure natural plant medicine Radix Angelicae Sinensis of the present invention, Radix Bupleuri, the Rhizoma Atractylodis Macrocephalae, Rhizoma Alismatis, the Radix Paeoniae Alba, Poria, Polyporus, Rhizoma Cyperi, Herba Leonuri, Herba Lycopi, Ramulus Cinnamomi.Experiment confirm has diuresis, reduces pharmacotoxicological effects such as capillary permeability, microcirculation improvement obstacle, raise immunity effect, at the existing symptomatic treatment of women's idiopathic edema etiological treatment is arranged also, have the Chinese medicine advantage and the characteristic of whole too many levels and treating both the principal and secondary aspects of a disease.

Summary of the invention

The object of the present invention is to provide medicine of a kind of treatment idiopathic edema evident in efficacy and preparation method thereof.

This drug invention people professor Wu Yiling finds that in practice idiopathic edema mostly is stagnation of liver-QI with deficiency of the spleen, qi depression to blood stasis and causing, and treatment is always with soothing liver and strengthening spleen, and activating blood and promoting diuresis is main.Idiopathic edema according to its clinical manifestation belong to the traditional Chinese medical science it " edema ", " general edema " reaches categories such as " anasarca ".Edema is attributed to lung, spleen, kidney three more in theory of Chinese medical science dirty, so-called " the fundamental cause of water disease being in the kidney, it is marked on lung, it is built in spleen ", and this is three dirty for the also many duties of treatment.Right idiopathic edema then can not be only explains that with the dirty mistake of lung, spleen, kidney three department Chinese medicine thinks that water gets the positive gas that then turns to, and is so incensed that the moon then turns to water, and the capable then water of gas is capable, and the stagnation of QI then water is poly-, the catharsis function of the too busy to get away liver that passes unimpeded of people's bromhidrosis.The irritability catharsis is proper, and then the popular water channel of mechanism of qi is freely sharp, and water liquid is thereupon about the lifting; Sending out otherwise then mechanism of qi pent-up, water liquid therefore are detained is edema.

Stagnation of liver-QI with deficiency of the spleen is the common pathogenesis of idiopathic edema, and this disease is more common in the not smooth middle-aged women of menoxenia, emotion, and symptoms such as the performance emotion is not smooth, anorexia, abdominal distention are relevant with menstrual cycle.The woman is congenital with liver, blood stored in the liver, and main catharsis, property happiness bar reaches, and stagnation of QI due to depression of the liver, the mechanism of qi disorder, the three warmers water channel is obstructed, and water liquid does not follow Chang Dao and overflows will send out in skin and is edema; " General Treatise on the Cause and Symptoms of Diseases ten water time " said: " blue or green water person, swollen all over the whole body from appearance earlier, its root is liver " illustrates that the liver failing to maintain the normal flow of QI can cause stagnation of QI water retention.Plain body weakness or stagnation of liver-QI all can cause spleen fortune not normal, through cloud: " all damp-edema completely all belong to spleen ", insufficiency of the spleen then can not transmitting and distributing the fluids, water is wet to stop poly-spreading unchecked and overflows so edema.Thereby the idiopathic edema pathologic basis is a stagnation of liver-QI with deficiency of the spleen.

It is an important step of morbidity that the channels stasis of blood stagnates, and channels is the hinge and the path of the defeated cloth circulation of qi-blood-body fluid, current QI and blood is arranged, ooze and moisten perfusion, Tianjin blood and effect such as ooze mutually.The operation of the network of meridians is called the gas network through gas, gas network depression and stagnation of QI, and it is warm supplements nutrition, defend to protect, information is passed on, regulate the control malfunction, the internal organs disfunction, the liver network stagnation of QI is smooth, the sighing frequently of emotion then, the tried out then abdominal distension and anorexia of the network gas of spleen; The network operation blood of venation also has gas in the blood, the venation depression and stagnation of QI, and regulatory function is not normal, and imbalance is oozed in the channels stasis of blood resistance then impaired Tianjin of its function blood mutually, and shows as " congestion water ", facial edema occurs, and both hands are swollen, afternoon lower extremity swelling and distension, the diseases such as depression of pressing.

This drug invention people Wu Yiling professor controls with soothing liver and strengthening spleen at this pathologic basis of stagnation of liver-QI with deficiency of the spleen, and the strong then liver catharsis function of spleen fortune could be normal, liver mechanism of qi bar reaches and is to keep normally fortune function of taste, harmonizing the functional activities of vital QI, tonneau three warmers, the essential condition that unclogs the channel; Simultaneously,, nourish blood and blood collateral dredging, the smooth network of gas, disperse blood stasis and dredge collateral, diuretic collateral dredging, recover the channels normal function to control all methods of network, it is stable to keep function, and edema is disappeared, and channels is logical, and liver mechanism of qi bar reaches, spleen fortune is strong, amounts to soothing liver and strengthening spleen, the effect of collateral dredging diuretic.

Medicine of the present invention is classified as monarch drug to work as; Radix Angelicae Sinensis, the little suffering of sweet in the mouth, warm in nature, return liver, the heart, spleen channel, the merit that nourishes blood with the blood collateral dredging is arranged.The disease of Radix Angelicae Sinensis master blood system nourishes blood and blood, " its sweet in the mouth and weighing is so specially can enrich blood; its gas is light and hot, thus again can promoting the circulation of blood, invigorating middle warmer has; in the row benefit is arranged, the gas medicine in the sincere blood, also the panacea in the blood is also " (" book on Chinese herbal medicine is just "), say in " Treatise on Febrile Disease with Notes ": " the arteries and veins person house of blood, all blood all belongs to the heart, the beneficial blood of all person's of promoting blood circulation heart elder generation's reinforcing the heart ", so with when being classified as monarch drug, command full side, broken stagnant blood, support fresh blood, nourish blood and the blood collateral dredging diuretic with collateral dredging.

Medicine of the present invention is a ministerial drug with Radix Bupleuri, Poria, Rhizoma Alismatis; Radix Bupleuri, bitter in the mouth, suffering, cold nature, Radix Bupleuri can bar reach irritability and dispersing the stagnated live-QI to relieve the stagnation of QI, and harmonizing the functional activities of vital QI, treatment Liver Channel melancholia, irritability bar reach then water reforms, " network with suffering for letting out ", and the smooth network of usefulness Radix Bupleuri gas, the mechanism of qi in the network is unobstructed, and then the network road is without hindrance.Poria, slightly sweet flavor, property is flat, GUIXIN, spleen, kidney channel.The Poria nature and flavor are all light, kind reason spleen soil, the eliminating dampness by diuresis of function invigorating spleen for diuresis, because of its property of medicine is gentle, diuretic and just do not hinder " book on Chinese herbal medicineization justice ": " Poria is the diuretic key medicine that dehumidifies the most, and book is said spleen invigorating, promptly water go and the strong certainly meaning of spleen also ".Rhizoma Alismatis, sweet light cold in nature, return kidney, urinary bladder channel, merit is apt to promoting diuresis to eliminate damp pathogen, and it is unfavorable to control functioning of bladder, water is wet to stop gathering dysuria, edema distension." Rhizoma Alismatis, abnormal smells from the patient is not sought fame and wealth and body constitution is light, thus the kind sluice way that oozes, specially can tonneau urine ... also can go into network with light, lightly can lead glue ear." (selecting from Zhang Shanlei " book on Chinese herbal medicine justice ") can ooze phlegm retention between sharp internal organs meridians, water is wet, makes heresy that outlet be arranged.With the Poria compatibility, to strengthen the promoting diuresis to eliminate damp pathogen effect.Three medicines share and are ministerial drug altogether, and reach soothing liver and strengthening spleen, the effect of inducing diuresis to remove edema.

Medicine assistant of the present invention is with the Rhizoma Atractylodis Macrocephalae, Polyporus, Herba Leonuri, Herba Lycopi, the Radix Paeoniae Alba, Rhizoma Cyperi; The Rhizoma Atractylodis Macrocephalae, bitter but sweet flavor, warm in nature, return spleen, stomach warp.Air making-up and spleen enlivening is arranged, the effect of dampness diuretic, " not Lu " says its kind " expectorant water, it is swollen to allowance for bark an edema due to wind pathogen knot ", for insufficiency of the spleen can not fortune and to cause water-damp retention particularly suitable, the compatibility Poria promotes spleen to transport, inducing diuresis to remove edema.Polyporus goes into kidney, urinary bladder channel, and sweet light oozing let out, promoting diuresis to eliminate damp pathogen and the humidity hysteresis of harnessing the river stays, and " herbal classic " said: " dredging water passages ", two Siberian cockleburs and usefulness strengthen diuretic and exempt from wet merit, make that water is wet to be separated from urine.Herba Leonuri, pungent drugs can disperse and bitter drugs can purge, the function blood circulation promoting and blood stasis dispelling, inducing diuresis to remove edema, Herba Leonuri is sliding and sharp, the water promoting the circulation of blood that disappears, eliminating blood stasis to promote regeneration of blood.The Herba Lycopi, the hot slightly warm in nature of bitter in the mouth has blood circulation promoting and blood stasis dispelling, the merit of line water detumescence.The hot temperature of loosing of Herba Lycopi is logical, and is cold not dry, and row and not high can soothing liver-QI gas and qualcomm meridian, and the merit of line water detumescence is arranged, and Herba Leonuri, Herba Lycopi's compatibility dispel the blood network stasis of blood to stagnate, and moves back edema, aqueous vapor down, tonneau urine and reach the effect of activating blood and promoting diuresis.The Radix Paeoniae Alba, the little acid of bitter in the mouth, kind easing the affected liver nourishing the liver, yin fluid astringing nourishes blood.Compatibility Radix Bupleuri is with easing the affected liver, and the liver body is cloudy and with sun, Radix Bupleuri, the Radix Paeoniae Alba match, and the liver body is strong and irritability is dredged, and its merit reaches certainly.Rhizoma Cyperi, perfume (or spice) is scurried circulation of qi promoting, is good at dispersing the stagnated live-QI to relieve the stagnation of QI, regulating functional activities of qi, the smooth network of gas.Compendium of Material Medica claims its " sharp three warmers are separated six kinds of stagnation-syndromes ", helps the effect of Radix Bupleuri depressed liver-energy dispersing and QI regulating, amounts to the meaning of " the capable then water of gas is capable ".

Ramulus Cinnamomi, acrid-sweet flavor, warm in nature.Suffering helps blood capable, sensible extremity, temperature three-way meridian, supporing yang activating QI.Medicine of the present invention is that assistant makes with Ramulus Cinnamomi, makes its promoting the circulation of blood branch, walks meridians, and temperature three-way meridian and draw all medicines and go into channels reaches extremity; Hot warm collateral dredging, compatibility Radix Angelicae Sinensis, Herba Leonuri, Herba Lycopi are with promoting blood circulation to remove obstruction in the collateral; The power that its a surname is logical again can activating YANG and prormoting functioning of QI, and it is wet to change YIN-cold water, helps Rhizoma Alismatis, and logical bladder is with diuresis under the guiding three warmers.

All medicines share, and the irritability bar is reached, the strong fortune of temper, and channels is unimpeded, and water is wet does not give birth to, and then edema is from disappearing.Be total to the long memorial liver spleen, the effect of collateral dredging diuretic.

Chinese medicine of the present invention can be had the Chinese medicine of same or similar effect fruit to replace, and these medical materials all can be concocted according to " national Chinese medicine processing standard " or " Chinese medicine voluminous dictionary ".

Medicine of the present invention is made by following bulk drugs:

Radix Angelicae Sinensis 159-240 part Radix Bupleuri 106-160 part Poria 212-322 part Rhizoma Alismatis 126-192 part

Rhizoma Atractylodis Macrocephalae 126-192 part Polyporus 126-192 part Herba Leonuri 318-482 part Herba Lycopi 126-192 part

Radix Paeoniae Alba 126-192 part Rhizoma Cyperi 105-159 part Ramulus Cinnamomi 105-159 part.

The weight ratio of medicine material medicine of the present invention is preferably:

192 parts of 322 portions of Rhizoma Alismatis of 160 parts of Poria of 240 parts of Radix Bupleuri of Radix Angelicae Sinensis

192 parts of 482 parts of Herba Lycopi of 192 parts of Herba Leonuris of 192 portions of Polyporus of the Rhizoma Atractylodis Macrocephalae

159 parts of 159 parts of Ramulus Cinnamomi of 192 portions of Rhizoma Cyperis of the Radix Paeoniae Alba.

The weight ratio of crude drug also is preferably in the Chinese medicine composition of the present invention:

126 parts of 322 portions of Rhizoma Alismatis of 106 parts of Poria of 159 parts of Radix Bupleuri of Radix Angelicae Sinensis

126 parts of 318 parts of Herba Lycopi of 192 parts of Herba Leonuris of 192 portions of Polyporus of the Rhizoma Atractylodis Macrocephalae

159 parts of 105 parts of Ramulus Cinnamomi of 192 portions of Rhizoma Cyperis of the Radix Paeoniae Alba.

192 parts of 212 portions of Rhizoma Alismatis of 160 parts of Poria of 240 parts of Radix Bupleuri of Radix Angelicae Sinensis

192 parts of 482 parts of Herba Lycopi of 126 parts of Herba Leonuris of 126 portions of Polyporus of the Rhizoma Atractylodis Macrocephalae

105 parts of 159 parts of Ramulus Cinnamomi of 126 portions of Rhizoma Cyperis of the Radix Paeoniae Alba.

160 parts of 267 portions of Rhizoma Alismatis of 133 parts of Poria of 200 parts of Radix Bupleuri of Radix Angelicae Sinensis

160 parts of 400 parts of Herba Lycopi of 160 parts of Herba Leonuris of 160 portions of Polyporus of the Rhizoma Atractylodis Macrocephalae

133 parts of 133 parts of Ramulus Cinnamomi of 160 portions of Rhizoma Cyperis of the Radix Paeoniae Alba.

172 parts of 248 portions of Rhizoma Alismatis of 144 parts of Poria of 186 parts of Radix Bupleuri of Radix Angelicae Sinensis

145 parts of 413 parts of Herba Lycopi of 154 parts of Herba Leonuris of 149 portions of Polyporus of the Rhizoma Atractylodis Macrocephalae

145 parts of 128 parts of Ramulus Cinnamomi of 161 portions of Rhizoma Cyperis of the Radix Paeoniae Alba.

The dosage form of medicine of the present invention is a kind of in capsule, tablet, powder, oral liquid, soft capsule, pill, tincture, syrup, suppository, gel, spray or the injection.

The active component of medicine of the present invention is made by the following step:

A) take by weighing in proportion and select the clean Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Rhizoma Cyperi, Herba Lycopi, add 6-10 times of water gaging, soaked 0.5-2 hour, steam distillation extracted volatile oil 4-7 hour, and volatile oil device is in addition collected, and oil yield is no less than 0.25%; Extracting solution filters, and is evaporated to 60 ℃ of mensuration relative densities to be 1.0-1.1, and is standby;

B) take by weighing in proportion and select clean Herba Leonuri, Poria, Polyporus extracting in water 3 times, add 10-15 times of water gaging for the first time, soaked 0.5-2 hour, extracted 1.5-3 hour; Add 10-13 for the second time, for the third time and doubly measure, extracted respectively 0.5-2.5 hour; Extracting solution filters, and merges to be evaporated to 60 ℃ of mensuration relative densities to be about 1.0-1.1, and is standby;

C) take by weighing in proportion and select clean Radix Angelicae Sinensis, Radix Bupleuri, Rhizoma Alismatis to add 60-80% ethanol, extract 2 times, add 6-9 for the first time and doubly measures, soaked 0.5-2 hour, extracted 1-3 hour; For the second time add 5-8 and doubly measure, extracted 1-3 hour; Extracting solution filters, and merges decompression recycling ethanol and is about 1.0-1.1 to measuring relative density at 60 ℃, and is standby;

D) the described standby concentrated solution of step a), step b) and step c) is merged, be evaporated at 60 ℃ and measure relative density 1.10～1.20, get clear paste, standby;

E) take by weighing in proportion and select the clean Radix Paeoniae Alba, be ground into the fine powder of 150-180 μ m;

The described fine powder of step d) gained clear paste and step e) constitutes the active component of this medicine jointly.

The preparation method of medicine capsule of the present invention is made by the following step:

F) step d) gained clear paste is a bed material with Radix Paeoniae Alba fine powder and appropriate amount of auxiliary materials, spray granulation, and 32 mesh sieve granulate, standby;

G) with a small amount of anhydrous alcohol solution of step a) gained volatile oil, spray in the granule, add appropriate amount of auxiliary materials, mix homogeneously, encapsulated airtight half an hour, promptly.

The clear paste that medicinal tablet of the present invention, powder, pill are the volatile oil that a) made by above-mentioned steps, step d) makes and the Radix Paeoniae Alba of proportional quantities, formulation method is made routinely.

The preparation method of medicine capsule of the present invention is preferably:

A) take by weighing in proportion and select the clean Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Rhizoma Cyperi, Herba Lycopi, add 8 times of water gagings, soaked 1 hour, steam distillation extracted volatile oil 5 hours, and volatile oil device is in addition collected, and oil yield is no less than 0.25%; Extracting solution filters, and is evaporated to 60 ℃ of mensuration relative densities to be 1.05, and is standby;

B) take by weighing in proportion and select clean Herba Leonuri, Poria, Polyporus extracting in water 3 times, add 13 times of water gagings for the first time, soaked 1 hour, extracted 2 hours; Add 11 times of amounts for the second time, for the third time, extracted respectively 1.5 hours, 1 hour; Extracting solution filters, and merges to be evaporated to 60 ℃ of mensuration relative densities to be about 1.05, and is standby;

C) take by weighing in proportion and select clean Radix Angelicae Sinensis, Radix Bupleuri, Rhizoma Alismatis to add 70% ethanol, extract 2 times, add 8 times of amounts for the first time, soaked 1 hour, extracted 2 hours; For the second time add 6 times of amounts, extracted 1.5 hours; Extracting solution filters, and merges decompression recycling ethanol and is about 1.05 to measuring relative density at 60 ℃, and is standby;

D) the described standby concentrated solution of step a), step b) and step c) is merged, be evaporated at 60 ℃ and measure relative density 1.10～1.15, get clear paste, standby;

Pharmaceutical dosage form of the present invention is a capsule, tablet, powder, oral liquid, soft capsule, pill, tincture, syrup, suppository, gel, a kind of in spray or the injection, for above-mentioned dosage form can be realized, need when these dosage forms of preparation, to add the pharmacy acceptable auxiliary, for example: filler, disintegrating agent, lubricant, suspending agent, binding agent, sweeting agent, correctives, antiseptic etc., filler comprises: starch, pregelatinized Starch, lactose, mannitol, chitin, microcrystalline Cellulose, sucrose etc., disintegrating agent comprises: starch, pregelatinized Starch, microcrystalline Cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose etc., lubricant comprises: magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc., suspending agent comprises: polyvinylpyrrolidone, microcrystalline Cellulose, sucrose, agar, hydroxypropyl emthylcellulose etc., binding agent comprises, starch slurry, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc., sweeting agent comprises: saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc., correctives comprises: sweeting agent and various essence, and antiseptic comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, the acetic acid chloroethene is fixed, the Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods.

The consumption of Chinese medicine composition of the present invention by active component crude drug gross weight, is 14-20 gram/day, but takes every day once or divide and take for 2-4 time, is preferably for 16.5 gram/days, divides and takes for 3 times.

For confirming the activity of Drug therapy idiopathic edema of the present invention, use the capsule 's content dry powder (to call medicine of the present invention in the following text) that makes by embodiment 1 method to carry out following pharmacological testing.

One, the diuresis of medicine of the present invention

1. experiment material

1.1 laboratory animal

The healthy SD rat, the cleaning level, female, 80, body weight 180～220g.Provide credit number by Hebei province's Experimental Animal Center: SCXK (Ji) 2003-1-003, quality certification numbering: DK0506-117.Animal feeding is in pharmacological room of Hebei Yiling Pharmaceutical Research Institute, illumination 12 hours/day, 20～23 ℃ of temperature, relative humidity 40～60%.Rat is raised in cages, 5/cage.Feedstuff is a full-valence pellet feed, is provided by Hebei province's Experimental Animal Center, keeps competent drinking-water.Experiment prospective adaptation raising three days.

1.2 experiment medicine

Medicine of the present invention, 4.6g crude drug/g dry powder is provided by Hebei Yiling Pharmaceutical Research Institute's company limited, makes suspension with 0.5%CMC-Na, 4 ℃ of preservations.

Furosemide acts on the renal tubules ascending thick limb of Henle's loop, and oral back diuresis began in 20～30 minutes, reaches the peak in 1～2 hour, continues 6～8 hours, and diuresis is powerful.

1.3 key instrument

MI-921D type electrolyte analyser, the magnificent more development in science and technology company limited in Shenzhen is made.

2. experimental technique

2.1 dosage setting principle

Clinical drug of the present invention is intended consumption 16.5g crude drug/sky, i.e. 0.275g crude drug/kg, and the dosage of the high, medium and low dosage group of setting rat is respectively 16,8,4 times of people's dosage, promptly 4.4,2.2,1.1g crude drug/kg, other establishes blank group, furosemide group.According to above dosage situation is set, rat is divided into following 5 groups, see Table 1:

Table 1 medicine of the present invention is to rat diuresis experiment grouping and dosage

2.2 medication

Gastric infusion, consistent with the oral route of clinical recommendation.Carry out every morning 8～9, continuous 15 days, adjusts the single administration volume according to body weight weekly.The furosemide group is only tested 1 administration on the same day.High dose is 0.44g crude drug/ml, presses the preparation of 1.0ml/100 gram the weight of animals.In, low dose group not isoconcentration administration of capacity such as uses.Successive administration 15 days.

2.3 experimental procedure

Whether rat put in the metabolic cage in advance conformed in 1 day, it is stable to observe free conditions of water drinking urine amount.Water is can't help in the 18h fasting before the screening, irritates deionized water 2.2ml/100g, collects the 2h urine, and the rat that screening urine amount surpasses 40% water load is used for experiment.Urine during by screening is measured balanced random packet, 10 every group.After the administration 15 days, gently press the rat lower abdomen to drain surplus urine, each is organized rat and irritates with normal saline 5ml/100g, and the saline of this concentration can make the outer liquid of zooblast increase Simulated Water sodium retention state.The furosemide group is irritated the equivalent saline that stomach contains medicine.Every metabolic cage amplifies 1 of Mus, collects 0-1h, 1-3h, 3-6h urine, detects the urine amount, urine K ⁺, Na ⁺, Cl ^-, pH value.

2.5 statistical method

Carry out non parametric tests and one factor analysis of variance with SPSS11.5.

3. experimental result

3.1 medicine of the present invention is to the influence of water load rat urine amount

Compare with the blank group, furosemide group rat urine amount in giving water load back 0-1h increases (P＜0.01), and the urine amount in 1-3h and the 3-6h has the trend of increase, total volume of urine increase (P＜0.01).Compare with the blank group, medicine 1.1g crude drug of the present invention/kg group rat only 3-6h urine amount increases (P＜0.05), and medicine 2.2 of the present invention, 4.4g crude drug/kg group rat also increase (P＜0.05) except that 3-6h urine amount increases (P＜0.01) total volume of urine.The results are shown in Table 1.

Table 1 medicine of the present invention to the influence of water load rat urine amount (

N=10)

Annotate: compare with the blank group, ^*P＜0.05, ^*P＜0.01

3.2 medicine of the present invention is to the influence of water load rat urine potassium, sodium, chlorine ion concentration

Compare furosemide group rat 0-1h urine Cl with the blank group ^-Concentration increases (P＜0.01), and 3-6h urine PH reduces (P＜0.05).Compare medicine 4.4g crude drug of the present invention/kg group rat 0-1h and 1-3h urine Cl with the blank group ^-Concentration increases (P＜0.05), 3-6h urine Cl ^-Concentration has the trend of increase.Compare medicine 2.2g crude drug of the present invention/kg group rat 1-3h urine Na with the blank group ⁺Concentration increases (P＜0.05).Compare medicine 1.1g crude drug of the present invention/kg group rat 1-3h urine Na with the blank group ⁺, Cl ^-Concentration increases (P＜0.05 or P＜0.01).The results are shown in Table 2.

Table 2 medicine of the present invention to the influence of water load rat urine ion concentration and pH value (

N=10)

Annotate: compare with the blank group, ^*P＜0.05, ^*P＜0.01

This experiment confirm medicine of the present invention can increase the urine amount of 3-6h, and medicine of the present invention does not have evident regularity to the influence of urine electrolyte concentration.Point out medicine of the present invention to have diuresis.

Two, medicine of the present invention is to the influence of capillary permeability

(1) medicine of the present invention is to the influence of mice mesentery capillary permeability

1 experiment material

1.1 laboratory animal

Healthy Balb/C mice, the cleaning level, female, 60, body weight 18～22g purchases the Experimental Animal Center in Hebei province, credit number: SCXK (Ji) 2003-1-003, quality certification numbering: DK050814.Animal identification adopts 5% picric acid labelling method.Raising is with mountain range academy pharmacological room, illumination 12 hours/day, 20～23 ℃ of temperature, relative humidity 40～60%.Mice is raised in cages, 6/cage.Mouse feed is a full-valence pellet feed, is provided by Hebei province's Experimental Animal Center, keeps competent drinking-water.Adaptability was raised three days.

1.2 experiment medicine

Medicine of the present invention, 4.6g crude drug/g medicated powder is provided by Hebei Yiling Pharmaceutical Research Institute's company limited.

Aspirin Enteric-coated Tablets, Ouyi Pharmaceutical Industry Co., Ltd., Shijiazhuang Pharmaceutical Group, the accurate word H13023635 of traditional Chinese medicines, batch number: 060510, specification: 25mg * 100 slice.

1.3 key instrument

The UV2550 spectrophotometer, day island proper Tianjin.

2 experimental techniques

2.1 dosage and grouping

The clinical plan consumption of this product 16.5g crude drug/sky, the dosage of setting the high, medium and low dosage group of mice is respectively 20,10,5 times of people's dosage, promptly 5.6,2.8,1.4g crude drug/kg.Other establishes model control group and aspirin group, totally 5 groups.See Table 3:

Influence experiment grouping and dosage that the mice mesentery capillary permeability that causes table 3 medicine Dichlorodiphenyl Acetate of the present invention increases

2.2 medication

The administration concentration of medicine high dose of the present invention is 0.06g medicated powder/ml, in, the medicinal liquid of low dose group forms by the dilution of high dose medicinal liquid, aspirin group administration concentration is 10mg/ml, more than all make suspension, 4 ℃ of preservations with 0.5%CMC-Na.Gastric infusion (consistent with the clinical oral administration route of administration), every morning 8～9 are carried out continuous 10 days.The administration volume is the 0.2ml/10g body weight.

2.3 experimental procedure

1h after last 1 administration, mouse tail vein injection 0.5% be according to the blue normal saline solution 0.1ml/10g of train of thought body weight, lumbar injection 0.6% acetic acid 0.1ml/10g immediately, and mice takes off cervical vertebra and puts to death behind the 20min.At abdominal scissors one osculum, divide several to wash the abdominal cavity with the 6ml normal saline, suction pipe sucking-off cleaning mixture merges the back and adds normal saline to 10ml, and the centrifugal 15min of 3000rpm gets supernatant in 590nm colorimetric determination absorbance.

2.4 statistical method

Adopt the SPSS11.5 statistical software to carry out one factor analysis of variance.

3 results

Compare with model control group, aspirin group OD value reduces (P＜0.05), and mice mesentery capillary permeability increases.Compare with model control group, each dosage group OD value of medicine of the present invention all reduces (P＜0.05 or P＜0.01).Illustrate that medicine of the present invention can reduce mice mesentery capillary permeability.The results are shown in Table 4.

The mice mesentery capillary permeability that causes table 4 medicine Dichlorodiphenyl Acetate of the present invention increases the influence of experiment absorbance

Annotate: compare with model control group, ^*P＜0.05, ^*P＜0.01

This result of the test shows, compares with model control group, and aspirin group OD value reduces (P＜0.05), and mice mesentery capillary permeability increases.Compare with model control group, each dosage group OD value of medicine of the present invention all reduces (P＜0.05 or P＜0.01).Point out medicine of the present invention that the effect that reduces the mesentery capillary permeability is arranged.

(2) medicine of the present invention is to the influence of mouse skin capillary permeability

1 experiment material

1.1 laboratory animal

Healthy Kunming mouse, the cleaning level, female, 60, body weight 18～22g.Purchase Experimental Animal Center, credit number: SCXK (Ji) 2003-1-003, quality certification numbering: DK0509025 in Hebei province.Animal identification adopts 5% picric acid labelling method.Raising is with mountain range academy pharmacological room, illumination 12 hours/day, 20～23 ℃ of temperature, relative humidity 40～60%.Mice is raised in cages, 6/cage.Mouse feed is a full-valence pellet feed, is provided by Hebei province's Experimental Animal Center, keeps competent drinking-water.Adaptability was raised three days.

1.2 experiment medicine

1.3 key instrument

The UV2550 spectrophotometer, day island proper Tianjin.

2 experimental techniques

2.1 dosage and grouping

Mice is divided into following 5 groups, sees Table 5:

Influence experiment grouping and dosage that table 5 medicine xylol of the present invention induced mice capillary of skin permeability increases

2.2 medication

Adopt gastric infusion, the 0.2ml/10g body weight, every morning 9～10 are carried out continuous 10 days.

2.3 experimental procedure

Mouse web portion center unhairing.1h mouse tail vein injection 0.5% is according to the blue normal saline solution 0.1ml/10g of train of thought body weight after last 1 administration, immediately on the skin of unhairing of position, mouse web portion center melted paraxylene 0.03ml/ only, mice takes off cervical vertebra and puts to death behind the 20min.Peel skin of abdomen, take off homalographic indigo plant with diameter 0.9cm card punch and dye skin, shredding to drop into operating scissors has in the plug teat glass, pours acetone-normal saline (7: 3) mixed liquor 10ml into, it is centrifugal next day to soak the back, gets supernatant in 610nm place colorimetric determination absorbance.

2.4 statistical method

Each is organized the result and compares with model control group, adds up with SPSS11.5.

2.3 result

Compare with model group, aspirin group mice OD value reduces (P＜0.01), illustrates that aspirin reduces the capillary of skin permeability.Compare with model group, medicine group 5.6g crude drug of the present invention/kg group reduces OD value (P＜0.01), and medicine group 2.8g crude drug of the present invention/kg group reduces OD value (P＜0.05).Point out medicine of the present invention can reduce the mouse skin capillary permeability.The results are shown in Table 2.

Table 6 medicine xylol of the present invention induced mice capillary of skin permeability increases influences experimental result

Annotate: compare with model control group, ^*P＜0.05, ^*P＜0.01

This test confirms that medicine of the present invention can reduce the mouse skin capillary permeability.

Three, medicine of the present invention is to the influence of microcirculation disturbance

(1) medicine of the present invention is to the microcirculatory influence of rat mesentery

By the influence experiment of medicine of the present invention to the rat mesentery microcirculation disturbance, evaluation is tried thing to be influenced internal organs are microcirculatory.96 female sd inbred rats are divided into 6 groups at random, blank group, model control group, Composite Salvia Dropping Pill group, medicine of the present invention 4.4,2.2,1.1g crude drug/kg group, 12 every group.Gastric infusion is 10 days continuously.Rat 20% urethane (0.7ml/100g) intraperitoneal injection of anesthesia about half an hour after last 1 administration.Cut off the abdominal cavity, pull out the part small intestinal, the part that has obvious blood capillary to distribute meso-ileum is tiled on the transparent object stage of 37 ℃ of water-baths.Under 10 times of object lens, measure fixedly caliber, velocity of blood flow, the calculating per second blood flow of blood vessel, vascular counts, the intersecting blood vessels number of observation field of excursion.After the administration 1 hour tail vein fast injection 10% high molecular dextran (6ml/kg) make model of microcirculation obstacle.5min, 15min, 30min, 45min, 60min observe These parameters respectively after the modeling.Calculate each rate of change of index constantly.Compare with model group, microcirculation number of blood vessel rate of change when 5min, 15min of medicine 1.1g crude drug of the present invention/kg group rat reduces (P＜0.01 or P＜0.05), and the caliber rate of change reduces (P＜0.05) when 30min, 45min and 60min.The rate of change of flow, number of blood vessel and intersecting blood vessels number reduces (P＜0.05) during the microcirculation 5min of medicine 2.2g crude drug of the present invention/kg group rat, have only intersecting blood vessels to count rate of change during 15min and reduce (P＜0.05), caliber, number of blood vessel rate of change reduce (P＜0.05) during 30min, have only blood vessel to count the reduction of rate of change (P＜0.01) when 45min and 60min.The rate of change of flow velocity, flow, number of blood vessel, intersecting blood vessels number all has reduction (P＜0.01 or P＜0.05) during the microcirculation 5min of medicine 4.4g crude drug of the present invention/kg group rat, the rate of change of all indexs all reduces (P＜0.01 or P＜0.05) when 15min, 30min, and caliber, flow velocity, flow change rate reduce (P＜0.01 or P＜0.05) when 45min and 60min.Point out medicine of the present invention can alleviate the mesentery microcirculation disturbance.

(2) medicine of the present invention is to the influence of Mice Auricle microcirculation disturbance

1 experiment material

1.1 laboratory animal

Healthy KM mice, the cleaning level, female, 120, body weight 18～22g purchases the Experimental Animal Center in Hebei province, credit number: SCXK (Ji) 2003-1-003, quality certification numbering: 603200.Animal identification adopts 5% picric acid labelling method.Raising is in pharmacological room of Medicine Research Academy of Hebei Medical University, illumination 12 hours/day, 20～23 ℃ of temperature, relative humidity 40～60%.Mice is raised in cages, 10/cage.Mouse feed is a full-valence pellet feed, is provided by Hebei province's Experimental Animal Center, freely drinks water.Adaptability was raised three days.

1.2 experiment medicine

FUFANG DANSHEN DIWAN, Tianjin Tasly Pharmaceutical Co., Ltd produces, authentication code: the accurate word Z10950111 of traditional Chinese medicines.

1.3 reagent

High molecular dextran, molecular weight 500,000, Shenzhen Herbon Polysaccharide Bio-technology Co., Ltd..

1.4 experimental apparatus

BI-2000 medical image analysis system, Chengdu TME Technology Co., Ltd..

2 experimental techniques

2.1 dosage and grouping

Mice is divided into following 6 groups at random by the body weight equilibrium, sees Table 7:

Table 7 medicine of the present invention is to the influence experiment grouping and the dosage of Mice Auricle microcirculation disturbance

2.2 medication

Each group is made up a prescription as solvent with 0.5% sodium carboxymethyl cellulose (CMC-Na).Gastric infusion, every morning 8～9 carry out, every Mus successive administration 10 days, and blank group and model control group give 0.5%CMC-Na.The administration volume is the 0.2ml/10g body weight.

2.3 experimental procedure

1h does the microcirculation inspection after every Mus 1 administration in the end.Mice 10% chloral hydrate intraperitoneal injection of anesthesia about half an hour after the administration.After the anesthesia, mice is lain on the back on the mice measuring platform, make auricle open and flat on measuring platform, drip a little liquid paraffin at measuring platform and auricle surface.Observe the Mice Auricle microcirculation.The record modeling before and modeling after 5,15,30,45, the little blood flow fluidised form of 60min auricle:

1) linear flow: blood flow is fast, be smooth streak, no granular sensation;

2) line grain stream: blood flow is very fast, is streak, and granular sensation is arranged slightly;

3) grain linear flow: blood flow is slower, though become line continuously, obvious granular sensation is arranged;

4) grain stream: blood flow is slow, and axial flow edge stream mixes, as the silt sample;

5) grain unhurried current: blood flow is the silt sample, continuously sluggish flow;

6) grain pendulum stream: blood flow is the silt shape, though flow swing forward;

7) stagnate: blood flow is stagnated motionless.

2.4 statistical method

Each group compares with model group, does rank test with SPSS11.5 software.

3 results

Respectively organize the little blood flow fluidised form of Mice Auricle microcirculation before the modeling and be 1,2,3 grade substantially, each group and the blank relatively zero difference of organizing.After the modeling, with the blank group relatively, the little blood flow fluidised form of model group Mice Auricle microcirculation rank increases (P＜0.05 or P＜0.01), and prolongs the microcirculation disturbance degree in time and increase the weight of.Compare with model group, the little blood flow fluidised form of Radix Salviae Miltiorrhizae drop pill group reduces (P＜0.05) in the 15min rank, and 45min and 60min rank reduce (P＜0.01).Compare with model group, medicine height of the present invention, middle dosage group 15,30,45 and 60min rank all reduce (P＜0.05 or P＜0.01).Compare with model group, rank reduces (P＜0.05 or P＜0.01) when medicine low dose group 15 of the present invention and 60min.The results are shown in Table 7-12.

Table 7 medicine of the present invention to the influence of Mice Auricle microcirculation disturbance experiment modeling before fluidised form

Table 8 medicine of the present invention to the influence of Mice Auricle microcirculation disturbance experiment modeling after the 5min fluidised form

Annotate: ^△Expression is compared P＜0.05 with the blank group

Table 9 medicine of the present invention to the influence of Mice Auricle microcirculation disturbance experiment modeling after the 15min fluidised form

Annotate: ^{△ △}Expression is compared P＜0.01 with the blank group; ^*Expression is compared P＜0.05 with model control group

Table 10 medicine of the present invention to the influence of Mice Auricle microcirculation disturbance experiment modeling after the 30min fluidised form

Annotate: ^{△ △}Expression is compared P＜0.01 with the blank group; ^*Expression is compared P＜0.05 with model control group; ^*Expression is compared P＜0.01 with model control group

Table 11 medicine of the present invention to the influence of Mice Auricle microcirculation disturbance experiment modeling after the 45min fluidised form

Table 12 medicine of the present invention to the influence of Mice Auricle microcirculation disturbance experiment modeling after the 60min fluidised form

Annotate: ^{△ △}Expression is compared P＜0.01 with the blank group; ^*Expression is compared P＜0.01 with model control group

3. conclusion

Medicine of the present invention has the effect of alleviating the Mice Auricle microcirculation disturbance that high molecular dextran causes.

Four, medicine of the present invention is to Immune Effects

(1) carbon clearance experiment

1 experiment material

1.1 laboratory animal

Healthy Balb/C mice, the cleaning level, female, 72, body weight 18～22g.Purchase Experimental Animal Center, credit number: SCXK (Ji) 2003-1-003, quality certification numbering: DK0506-0059 in Hebei province.Animal feeding is in pharmacological room of Medicine Research Academy of Hebei Medical University, and mice is raised in cages, and 6/cage, illumination 12 hours/day, 20～23 ℃ of temperature, relative humidity 40～60%.Feedstuff is a full-valence pellet feed, is provided by Hebei province's Experimental Animal Center.Freely drink water.Adaptability was raised 3 days.

1.2 experiment medicine

Cyclophosphamide, Hualian Pharmaceutical Co., Ltd., Shanghai, the accurate word (1995) of medicine is defended No. 012034 in Shanghai, product batch number: 050309.Levamisole, Hunan Dongting Pharmaceutical Co., Ltd., lot number: 060417.

1.3 key instrument

The UV2550 spectrophotometer, day island proper Tianjin.

1.4 main agents

India ink, Beijing are sincerely believed in meticulous preparation factory, specification: 100ml/ bottle, lot number: 40823.

2 experimental techniques

2.1 dosage and grouping

Clinical drug of the present invention is intended consumption 16.5g crude drug/sky, i.e. 0.28g crude drug/kg, and setting dosage is 5.6g crude drug/kg, 2.8g crude drug/kg, 1.4g crude drug/kg/d, is equivalent to intend 20,10,5 times of clinical human dosage respectively.Other establishes blank group and model group, sees Table 13.

Table 13 medicine of the present invention is to the influence experiment grouping and the dosage of immunologic hypofunction mice non-specific immunity

2.2 medication

Drug administration concentration of the present invention is respectively 0.06g medicated powder/ml, 0.03g medicated powder/ml, 0.015g medicated powder/ml.Adopt gastric infusion (identical), 0.2ml/10g, successive administration 14 days with clinical recommendation approach.Cyclophosphamide is continuous intraperitoneal injection 2 times at the 12nd and 13 day, 40mg/kg.The levamisole administration concentration is 2.25mg/kg, irritates the stomach successive administration 14 days, 0.2ml/10g.

2.3 detect index and detection method

Behind the last administration 24h, every caudal vein is injected 20% india ink 0.1ml/10g body weight, in 1 (t ₁) and 10 (t ₁₀) minute after, get blood 20 μ l from the eye socket vein respectively, be added to 2ml0.1%Na ₂CO ₃Shake up in the solution, with microplate reader colorimetric under 680nm, photometry density (the following OD that uses respectively ₁And OD ₁₀Represented 1 minute and the optical density of 10 minutes institute's blood samplings), be calculated as follows and clean up index K value.

The K value after body weight and liver spleen heavily convert, phagocytic index α value:

2.4 statistical method

Carry out one factor analysis of variance with SPSS11.5 software.

3 results

With the blank group relatively, model control group clean up index K and phagocytic index α all reduces (P＜0.01).With model control group relatively, the levamisole group clean up index K and phagocytic index α raise (P＜0.01).With model control group relatively, medicine 5.6g crude drug of the present invention/kg group clean up index K and phagocytic index α raise (P＜0.01).2.8g the index K that cleans up of crude drug/kg group raises (P＜0.05), phagocytic index α has trend of rising.

Table 14 medicine of the present invention to immunologic hypofunction mouse monokaryon macrophage function influence the result ( N=12)

Annotate: compare with the blank group, ^{△ △}P＜0.01; Compare with model control group, ^*P＜0.05, ^*P＜0.01

By the experiment of mice carbon clearance, point out the mononuclear phagocyte function of the low mice of medicine energy raise immunity of the present invention.

(2) serum hemolysin experiment

1 experiment material

1.1 laboratory animal

Healthy Balb/C mice, the cleaning level, female, 72, body weight 18～22g purchases the Experimental Animal Center in Hebei province, credit number: SCXK (Ji) 2003-1-003, quality certification numbering: DK0507-0032.Raising is in pharmacological room of Medicine Research Academy of Hebei Medical University, illumination 12 hours/day, 20～23 ℃ of temperature, relative humidity 40～60%.Mice is raised in cages, 6/cage.Mouse feed is a full-valence pellet feed, is provided by Hebei province's Experimental Animal Center.Freely drink water.Adaptability was raised three days.

1.2 experiment medicine

Cyclophosphamide, Hualian Pharmaceutical Co., Ltd., Shanghai, the accurate word (1995) of medicine is defended No. 012034 in Shanghai, product batch number: 050309.

Levamisole hydrochloride (positive drug) is provided by Hunan Dongting Pharmaceutical Co., Ltd., the accurate word H43020589 of traditional Chinese medicines, batch number: 050330.

1.3 key instrument

The UV2550 spectrophotometer, day island proper Tianjin.

1.4 experiment reagent

SRBC preserves liquid (Alsever liquid): glucose 2.05g, and sodium chloride 0.42g, sodium citrate 0.8g, distilled water 100ml, 8 pounds of 10 minutes sterilization backs are standby.

Dou Shi reagent (survey hemoglobin usefulness,, produce color reaction): sodium bicarbonate 1.0g, high-potassium ferricyanide 0.2g, potassium cyanide 0.05g, distilled water 1000ml in conjunction with hemoglobin.

Complement: fresh Cavia porcellus (at least 3) pooled serum is centrifugal after 30 minutes in 4 ℃ of absorptions through hematocrit SRBC (10: 1), gets supernatant, puts below-20 ℃ standby.Every Cavia porcellus has 10ml blood approximately, gets 3ml serum approximately.

SRBC: under aseptic condition, get blood from healthy adult sheep external jugular vein, put blood (SRBC that adds 2 times of amounts in advance preserves liquid) jog 10 minutes in the conical flask that bead is arranged and defibrinate to remove, it is standby to put 4 ℃ of refrigerators, can preserve for 3 weeks.Face the time spent with normal saline washing 3 times, got packed red cells in centrifugal 10 minutes, press the desired concn dilution again through 2000rpm.

2 experimental techniques

2.1 dosage and grouping

Mice is divided into following 6 groups at random by the body weight equilibrium, sees Table 15:

Table 15 medicine mice serum of the present invention hemolysin experiment grouping and dosage

2.2 medication

The administration concentration of medicine high dose of the present invention is 0.06g medicated powder/ml, in, the medicinal liquid of low dose group forms by the dilution of high dose medicinal liquid, the administration concentration of levamisole group is 2.25mg/ml, more than all make suspension, 4 ℃ of preservations with 0.5%CMC-Na.Gastric infusion (consistent with the clinical oral administration route of administration), every morning 8～9 are carried out continuous 10 days.The administration volume is the 0.2ml/10g body weight.

2.3 experimental procedure

The 11st day mouse peritoneal injection 0.2ml 50%SRBC.12nd, 13 days intraperitoneal injection of cyclophosphamide 30mg/kg, once a day.1h after last 1 administration in the 15th day, infraorbital vein is got blood, and separation of serum supplies that serum dilution (general more than 500 times) back measure.Hemolytic reaction: add diluted serum 1ml in the reaction tube successively, 5%SRBC 0.5ml, 10% complement 1ml, put in 37 ℃ of waters bath with thermostatic control and be incubated 30 minutes, move to cessation reaction in the ice bath then, centrifugal 5 minutes of 1500rpm gets supernatant 50 μ l and adds Dou Shi reagent 150 μ l on ELISA Plate, shake up and placed 10 minutes, use microplate reader in 540nm wavelength measurement absorbance.The SRBC half hemolysis value: get 5%SRBC 0.25ml and add Dou Shi liquid to 4ml, colorimetric reads absorbance, the absorbance when being used SRBC HD50 in the experiment.Calculate: sample cell half hemolysis value (HC ₅₀) be calculated as follows.

2.4 statistical method

Adopt SPSS 11.5 statistical softwares to do non parametric tests.

3 results

Compare the HC of model control group with the blank group ₅₀Reduce (P＜0.01).Compare the HC of levamisole group mice with model control group ₅₀Raise (P＜0.01).Compare with model control group, compare, the HC of medicine 5.6g crude drug of the present invention/kg group with model control group ₅₀Increase (P＜0.05).The results are shown in Table 16.

Table 16 medicine group of the present invention mice serum hemolysin experimental result (

N=12)

Annotate: compare with the blank group, ^{△ △}P＜0.01; Compare with model group, ^*P＜0.05, ^*P＜0.01

By the experiment of mice serum hemolysin, point out the humoral immune function of the low mice of medicine energy raise immunity of the present invention.

(3) spleen lymphocyte proliferation experiment

Study medicine of the present invention to humoral immunization and immune function influence by the spleen lymphocyte proliferation experiment.96 Healthy female Balb/C mices are divided into 8 groups at random, are respectively the blank group, model control group, levamisole group, medicine 6.30,4.20,2.80,1.87 of the present invention and 1.24g crude drug/kg, 12 every group.Gastric infusion is 12 days continuously.The 9th, 10 days intraperitoneal injection of cyclophosphamide 30mg/kg of administration, once a day.Put to death mice on the 12nd day, the preparation splenocyte suspension is with molten broken liquid washing splenocyte.Glacial acetic acid with 3% carries out cell counting, and viable count needs more than 95%.It is standby that cell is diluted to 1 * 106/ml concentration with culture fluid.On super-clean bench, splenocyte is added in the aseptic culture plate hole, every hole 200 μ l, each sample repeats the 3-4 hole.Add Con-A or LPS.Put into the 5%CO2 incubator, cultivated 72 hours.Stop cultivating preceding 6 hours, every hole adds 3H-TdR1 μ l, and making its final concentration is 1～5 μ ci/ml.With micro-bull cell harvesting instrument cell is pumped on the 49 type glass fiber filter paper.Put 80 ℃ of baking oven inner dryings 30 minutes.The filter paper of oven dry is put into the bottle that fills scintillation solution, with the activity (cpm) of liquid scintillation instrument working sample.Each group residue animal is got thymus, and spleen is weighed, and calculates organ index.Compare the Con-A activity and the LPS activity rising (P＜0.01) of medicine 6.3g crude drug of the present invention/kg group with model group.1.24g the Con-A activity of crude drug/kg group raises (P＜0.01), the LPS activity has trend of rising.The dose-effect relationship of medicine of the present invention is " U " type.Compare with the blank group, model group mouse thymus index reduces (P＜0.05).Point out medicine of the present invention to the low mouse spleen lymphocyte multiplication capacity of raise immunity.Dose-effect relationship is " U " shape.

Acute toxicity testing is the result show, continuous 3 Cmaxs in medicine 331.2g crude drug/kg of the present invention a day, and the maximum volume administration, mice does not see the overt toxicity reaction.This dosage is equivalent to the people and intends 1204 times of clinical dosage.

The rat long term toxicity test is the result show, the rat long term administration does not have the overt toxicity reaction under medicine 4.2g of the present invention, 8.4g, the 16.8g crude drug/kg dosage.

In sum, medicine of the present invention has diuresis, reduces the effect of capillary permeability, alleviation microcirculation disturbance and raise immunity, at the existing symptomatic treatment of idiopathic edema etiological treatment is arranged also, have the Chinese medicine advantage and the characteristic of whole too many levels and treating both the principal and secondary aspects of a disease.

The specific embodiment

Following embodiment is used to illustrate the preparation of medicine of the present invention, but it can not constitute any restriction to scope of the present invention.

Embodiment 1

The preparation of medicine capsule of the present invention (temporary called after: return the Siberian cocklebur swell dispersing capsule):

Prescription:

Radix Angelicae Sinensis 200 gram Radix Bupleuri 133 gram Poria 267 gram Rhizoma Alismatis 160 grams

The Rhizoma Atractylodis Macrocephalae 160 gram Polyporus 160 gram Herba Leonuris 400 gram Herba Lycopi 160 grams

The Radix Paeoniae Alba 160 gram Rhizoma Cyperis 133 gram Ramulus Cinnamomi 133 grams

Preparation method:

D) the described standby concentrated solution of step a), step b) and step c) is merged, be evaporated at 60 ℃ and measure relative density 1.14, get clear paste, standby;

Embodiment 2

The preparation of medicinal tablet of the present invention:

Prescription:

Radix Angelicae Sinensis 186 gram Radix Bupleuri 144 gram Poria 248 gram Rhizoma Alismatis 172 grams

The Rhizoma Atractylodis Macrocephalae 149 gram Polyporus 154 gram Herba Leonuris 413 gram Herba Lycopi 145 grams

The Radix Paeoniae Alba 161 gram Rhizoma Cyperis 128 gram Ramulus Cinnamomi 145 grams

Preparation method:

A) take by weighing in proportion and select the clean Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Rhizoma Cyperi, Herba Lycopi, add 6-10 times of water gaging, soaked 0.5 hour, steam distillation extracted volatile oil 4 hours, and volatile oil device is in addition collected, and oil yield is no less than 0.25%; Extracting solution filters, and is evaporated to 60 ℃ of mensuration relative densities to be 1.0, and is standby;

B) take by weighing in proportion and select clean Herba Leonuri, Poria, Polyporus extracting in water 3 times, add 10-15 times of water gaging for the first time, soaked 0.5 hour, extracted 1.5 hours; Add 10 times of amounts for the second time, for the third time, extracted respectively 0.5 hour; Extracting solution filters, and merges to be evaporated to 60 ℃ of mensuration relative densities to be about 1.0, and is standby;

C) take by weighing in proportion and select clean Radix Angelicae Sinensis, Radix Bupleuri, Rhizoma Alismatis to add 60-80% ethanol, extract 2 times, add 6 times of amounts for the first time, soaked 0.5 hour, extracted 1 hour; For the second time add 5 times of amounts, extracted 1 hour; Extracting solution filters, and merges decompression recycling ethanol and is about 1.0 to measuring relative density at 60 ℃, and is standby;

D) the described standby concentrated solution of step a), step b) and step c) is merged, be evaporated at 60 ℃ and measure relative density 1.10, get clear paste, standby;

G) make tablet according to a conventional method.

Embodiment 3

The preparation of drug powder of the present invention:

Prescription:

Radix Angelicae Sinensis 240 gram Radix Bupleuri 160 gram Poria 212 gram Rhizoma Alismatis 192 grams

The Rhizoma Atractylodis Macrocephalae 126 gram Polyporus 126 gram Herba Leonuris 482 gram Herba Lycopi 192 grams

The Radix Paeoniae Alba 126 gram Rhizoma Cyperis 159 gram Ramulus Cinnamomi 105 grams

Preparation method:

A) take by weighing in proportion and select the clean Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Rhizoma Cyperi, Herba Lycopi, add 6-10 times of water gaging, soaked 2 hours, steam distillation extracted volatile oil 7 hours, and volatile oil device is in addition collected, and oil yield is no less than 0.25%; Extracting solution filters, and is evaporated to 60 ℃ of mensuration relative densities to be 1.1, and is standby;

B) take by weighing in proportion and select clean Herba Leonuri, Poria, Polyporus extracting in water 3 times, add 15 times of water gagings for the first time, soaked 2 hours, extracted 3 hours; Add 13 times of amounts for the second time, for the third time, extracted respectively 2.5 hours; Extracting solution filters, and merges to be evaporated to 60 ℃ of mensuration relative densities to be about 1.1, and is standby;

C) take by weighing in proportion and select clean Radix Angelicae Sinensis, Radix Bupleuri, Rhizoma Alismatis to add 80% ethanol, extract 2 times, add 9 times of amounts for the first time, soaked 2 hours, extracted 3 hours; For the second time add 8 times of amounts, extracted 3 hours; Extracting solution filters, and merges decompression recycling ethanol and is about 1.1 to measuring relative density at 60 ℃, and is standby;

D) the described standby concentrated solution of step a), step b) and step c) is merged, be evaporated at 60 ℃ and measure relative density 1.20, get clear paste, standby;

F) conventional method is made powder.

Embodiment 4

The preparation of medicine oral liquid of the present invention:

Prescription:

Radix Angelicae Sinensis 159 gram Radix Bupleuri 106 gram Poria 322 gram Rhizoma Alismatis 126 grams

The Rhizoma Atractylodis Macrocephalae 192 gram Polyporus 192 gram Herba Leonuris 318 gram Herba Lycopi 126 grams

The Radix Paeoniae Alba 192 gram Rhizoma Cyperis 105 gram Ramulus Cinnamomi 159 grams

Preparation method:

Make oral liquid according to a conventional method.

Embodiment 5

The preparation of medicinal soft capsule of the present invention:

Prescription:

Radix Angelicae Sinensis 240 gram Radix Bupleuri 160 gram Poria 322 gram Rhizoma Alismatis 192 grams

The Rhizoma Atractylodis Macrocephalae 192 gram Polyporus 192 gram Herba Leonuris 482 gram Herba Lycopi 192 grams

The Radix Paeoniae Alba 192 gram Rhizoma Cyperis 159 gram Ramulus Cinnamomi 159 grams

Preparation method:

Make soft capsule according to a conventional method.

Embodiment 6

The preparation of bolus of drug of the present invention:

Prescription:

Preparation method:

Make pill according to a conventional method.

Embodiment 7

The preparation of medicinal tincture of the present invention:

Prescription:

Radix Angelicae Sinensis 159 gram Radix Bupleuri 106 gram Poria 212 gram Rhizoma Alismatis 126 grams

The Rhizoma Atractylodis Macrocephalae 126 gram Polyporus 126 gram Herba Leonuris 318 gram Herba Lycopi 126 grams

The Radix Paeoniae Alba 126 gram Rhizoma Cyperis 105 gram Ramulus Cinnamomi 105 grams

Make tincture according to a conventional method.

Embodiment 8

The preparation of medical syrup agent of the present invention:

Prescription:

Preparation method:

Make syrup according to a conventional method.

Embodiment 9

The preparation of drug suppository of the present invention:

Prescription:

Preparation method:

Make suppository according to a conventional method.

Embodiment 10

The preparation of medicament gelling agent of the present invention:

Prescription:

Preparation method:

Make gel according to a conventional method.

Embodiment 11

The preparation of medicament spraying agent of the present invention:

Prescription:

Preparation method:

Make spray according to a conventional method.

Embodiment 12

The preparation of drug injection of the present invention:

Prescription:

Preparation method:

Make injection according to a conventional method.

Claims

1. medicine for the treatment of idiopathic edema is characterized in that being being made by the crude drug of following weight portion ratio:

2. medicine according to claim 1, the weight portion ratio of its crude drug is:

3. medicine according to claim 1, the weight portion ratio of its crude drug is:

4. medicine according to claim 1, the weight portion ratio of its crude drug is:

5. medicine according to claim 1, the weight portion ratio of its crude drug is:

6. medicine according to claim 1, the weight portion ratio of its crude drug is:

7. according to the arbitrary described medicine of claim 1-6, it is characterized in that this pharmaceutical dosage form is capsule, tablet, powder, oral liquid, pill, tincture, syrup, suppository, gel, spray or injection.

8. according to the arbitrary described medicine of claim 1-6, it is characterized in that the active component of this medicine is made by the following step:

9. the preparation method of the described medicine capsule of claim 7 is characterized in that may further comprise the steps:

10. according to the preparation method of the described capsule of claim 9, it is characterized in that may further comprise the steps:

11. the preparation method of the described medicine of claim 7 is characterized in that may further comprise the steps:

The volatile oil that step a) in the claim 9 is made, the clear paste that step d) makes and the Radix Paeoniae Alba of proportional quantities, formulation method is made tablet, powder, pill routinely.