CN100491366C - Use of wogonin as medicament for treatment of anxiety - Google Patents
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Abstract
A method for preventing or for treating anxiety in a patient in need thereof comprising administering wogonin to the patient in an effective dose that does not cause sedative or myorelaxant side effects. Methods for extracting wogonin from the roots of scutelleria baicalensis Georgi are also described.
Description
Technical field
The present invention relates to wogonin (Wogonin) as the new purposes of treatment with the medicine of the related anxiety disorder in Benzodiazepine site.
Background technology
Benzodiazepine (BZDs) class medicine is very effective anxiolytic, also is the prescription drugs that is widely used in treating mental disease at present.Yet BZDs class medicine shows undesirable side effects, comprises calm and of flaccid muscles.
The root of large-flowered skullcap (Scutellaria baicalensis Georgi or be the Ougon of Japanese) is a kind of very important traditional herbal medicine.It can be antibiotic, sedative effect is arranged and can be used for treating many diseases, comprises diarrhoea (Kubo, M., et al, Planta Medica 43:194-20,1981) and hepatitis (Kimuya, Y., et al, Chem Pharm Bull 29:2610-2617,1981).
Several different compounds, comprise wogonin, scutellarin, baicalin, scutellarein and Scutellaria flavones from then on herbal medicine extract and carried out GABA
AThe avidity test in the Benzodiazepine site (BZD-S) of acceptor removes to determine to be suitable for doing the further strong binding partner of research.Report about yellow Cen extract binding ability is mutual contradictory (Hui, KM, et al., Planta Med 5691-93,2000).
Summary of the invention
The present invention is based on unexpected discovery to small part: the tool chemical formula
Compound (be called wogonin usually, very effective angst resistance effect Wogonin) is provided and can cause calm and undesirable action of flaccid muscles.Test on live body, its effect was not expected, and this is because the Chinese
Scutellarin is to GABA
AThe avidity of the BZD-S of acceptor by existing report or weak or medium, is strong part to its acceptor and it be not decided to be.Yet we study with the generally accepted model of industry, have obtained unexpected positive result, have shown its effect antianxity.As anxiolytic medicament many advantages are arranged with wogonin.This compound is contained in root of large-flowered skullcap herbal medicine root, be natural generation, and known its toxicity is very low.This compound content in this herbal medicine is abundant, can extract efficiently and economically.The high method of collecting rate and highly purified this compound of extraction also is provided.
In an example, the invention provides the method that a kind of preparation has above-mentioned chemical formula compound, comprise with solvent filter, the xln that concentrates and form this compound from the precipitate that has concentrated.Special example, scutellariae,radix is a pulvis.Solvent can be methylene dichloride or ethanol.The product leaching process can carry out gentle the depressing of standard temperature.The purity of this xln can reach 85-99%.Finished product is collected rate 0.2%-0.8%.
In another example, the invention provides and a kind ofly obtain this product from above-mentioned compound method.This product is at pharmaceutically acceptable a kind of prescription.
In another example, the invention provides and a kind ofly make the medicament of treatment anxiety disorder with wogonin.Special example, wogonin are the medicaments that is used for making the treatment anxiety disorder of no calmness and/or myorelaxant effects.
In another example, the present invention proposes with medicament treatment anxiety disorder.This medicament mainly is made up of the compound of above-mentioned chemical formula.
Again in another example, effective non-toxic that the invention provides doses a patient with has a compound of above-mentioned chemical formula is treated anxiety disorder, and this dosage provides angst resistance effect and do not have calm and undesirable action of flaccid muscles.
In a special example, the dosage that patient takes is to about 1.0mg/kg from 0.15mg/kg.Dosage can be first-class divided dose, also can be more than a five equilibrium dosage.
On the other hand, the invention provides a kind of cartridge bag, this cartridge bag contains one or more containers that are full of this compound.This cartridge bag also can be equipped with the specification sheets with this compounds for treating anxiety disorder.
Again in another example, the invention provides a kind of method for the treatment of anxiety disorder, this method is the wogonin of effective non-toxic of dosing a patient with.
Description of drawings
Fig. 1 is the Photomicrograph of wogonin, shows its needle-like crystal.
Fig. 2 is the exemplary currents trace (n=6) that utilizes patch clamp (whole-cell patch clamp) technology to obtain from dorsal root ganglion (DRG) neurone.
Fig. 3 represents, mouse oral vehicle or medicine were tested in given 5 minutes in elevated plus-maze test, and be acute or chronic after taking medicine 1 hour, test-results, comprise that control group, stable (Diazepam) group and wogonin (Wogonin) organize.
Fig. 4 represents, mouse oral vehicle or medicine were tested in given 5 minutes in elevated plus-maze test, and be acute or chronic after taking medicine 1 hour, test-results, comprise control group, Wogonin group and Wogonin+Ro15-1788 group.
Fig. 5 represents, mouse oral vehicle or medicine were tested in given 5 minutes in elevated plus-maze test, and after taking medicine 1 hour, acute or chronic test-results comprises control group, Diazepam and Wogonin group.
Embodiment
The present invention above and other purpose, characteristic and advantage will illustrate by following preferred embodiment and accompanying drawing thereof.
Below, example of the present invention is described
The present invention is based on unexpected discovery to small part: the tool chemical formula
Compound (being called wogonin (Wogonin) usually), it can provide very effective angst resistance effect and can not cause calm and undesirable action of flaccid muscles.Test on live body, its effect was not expected, this be since wogonin to GABA
AThe avidity of the BZD-S of acceptor by existing report, or weak or medium, is strong part to its acceptor and it be not decided to be.Yet we study with the generally accepted model of industry, have obtained the result in unexpected front, have shown its effect antianxity.As anxiolytic medicament many advantages are arranged with Wogonin.This compound is contained in root of large-flowered skullcap herbal medicine root, be natural generation, and known its toxicity is very low.This compound content in this herbal medicine is abundant, can extract efficiently and economically.
The invention provides the method that high yield and high purity ground extracts this compound.This method comprises from scutellariae,radix to be extracted, and it contains a large amount of Wogonin.Contain the herbal medicine of Wogonin as other, in process for preparation, other composition of root of large-flowered skullcap herbal medicine also can be utilized.Table 1 is listed the part herbal medicine that contains Wogonin.
Table 1
| Scutellaria class plant |
| The root of large-flowered skullcap (Scutellaria baicalensis Georgi) |
| S.amonea C.H.Wright |
| S.barbata D.Don(S.rivularis Wall) |
| S.hypericifolia Levl. |
| S.indica L. |
| S.likiangensis Diels |
| S.planipes |
| S.rehderiana Diels. |
| S.strigillosa Hemsl. |
| S.tenax W.W.Smith var.patentipilosa |
| S.viscidula Bunge |
| Other belongs to the class plant |
| Sorbaria sorbifolia |
| Tetracera indica |
Before extracting compound, by pulverizing, grind or other method being made careful powder with herbal medicine.Leaching process can utilize chlorinated solvent, for example methylene dichloride, trichloromethane, or alcohol, for example methyl alcohol, ethanol, n-butanols.Ether, acetone, ethyl acetate, and other common solvent.Can finish and comprise 1,2,3,4,5,6 or the more extraction of more number.Extraction can be carried out under standard temperature and pressure (STP), for example 25 ℃ and one normal atmosphere of temperature.Also can under other temperature and pressure, carry out.In special example, extraction can be carried out under the boiling point of the solvent that is used to extract.
Extract can filter with appropriate means, comprises using standard filter paper.The also available any suitable method of extract concentrates, and comprises and uses vaporizer.
The xln of compound can obtain by dissolving extract in alcoholic acid solvent for example, and allows it at room temperature to stop one suitable period.These xln can be with suitable solvent, and for example ethanol filters and cleans.
Also available other method as an example.
The described method that is used for producing this product is collected the high and purity height of rate.The purity of product generally can reach 85-99%, and average about 95%.Finished product is collected rate 0.2%-0.8%, and promptly every 100g root of large-flowered skullcap can be produced 0.2-0.8gWogonin.
This product height nontoxicity, the half lethality rate (LD50) of mouse is about 4g/kg.
The Wogonin product of being produced is very effective to the treatment anxiety disorder.It not only reduces the symptom that is associated with anxiety effectively, and the following Example confirmation, does not also produce undesirable calmness and muscle relaxation effect even take high dosage.Usually, the patient who suffers from anxiety disorder takes Wogonin with effective non-toxic.Though take Wogonin several different methods is arranged, comprise oral, bowel lavage, collunarium, filling vagina and parenteral injection, suggestion is adopted oral.
" effectively non-toxic " is meant the amount of compound or on physiology or the compound composition that pharmaceutically contains herein, and be effective to the function that provides it to desire to reach, and for example can treat anxiety disorder, and the nontoxicity untoward reaction.The variation of its effective non-toxic is depended on such as body sizes and age so that the severity of the state of an illness.Be subjected to the people of common training can analyze above-mentioned factor and went to determine effective non-toxic, and need not the over-drastic experiment.Special example, dosage is about 0.6mg/kg to being about 1.0mg/kg, and recommended doses is about 0.1mg/kg to being about 0.7mg/kg, and recommended dose is about 0.15mg/kg to being about 10.35mg/kg.Can singly wait branch dosage or 2,3,4,5 or more five equilibrium dosage take.
Wogonin is acute all effective with chronic anxiety to treating.When needs, they are suitable for large dose oral administration, and also low dose is taken for a long time.For example, when patient suffers from a kind of critical anxiety disorder, when " panic attack ", can an excess dosage take.Can also smaller dose take for a long time and control anxiety.Special example is that Wogonin can take before operation, uses and reduces anxiety and relax mood.This kind therapy not only alleviates patient's intense strain, and can make that the narcotic consumption minimizes when performing an operation.
The Wogonin that takes can be the form that method that the present invention narrates is produced, and can also be pharmaceutically and the form that acceptable composition mixes on physiology with multiple." pharmaceutically and on physiology accepting " is meant those compounds, contains the synthetics and/or the dosage form of these compounds herein, and they reasonably are being fit to use under the medical judgment category.
Compound of the present invention can be independently, and perhaps the form with salt exists when being fit to.In the time that solubleness will be increased, will make salifiable form.At acceptable salt pharmaceutically and on physiology and their preparation is that the professional is known.These salt at pharmaceutically acceptable compound comprise the traditional non-toxic salts be made up of sodium, calcium and magnesium or quaternary ammonium salt that gets from chemosynthesis inorganic or organic acid or alkali.
The present invention has also described pharmaceutically and physiological synthetics, and they comprise medicable compound dosage and carrier pharmaceutically or vehicle.Carrier comprises salt solution, buffer saline, glucose, water, glycerine, ethanol and their combination.If any requiring, its composition can comprise wetting agent or emulsifying agent or pH buffer reagent in a small amount.Its composition can be liquid solvent, suspension, emulsion, tablet, pill, capsule, lasting formulating of recipe or the pulvis that discharges.Its composition can be to have conventional adhesive and such as the suppository of tri-glyceride carrier.Formula of oral can comprise such as medicine level N.F,USP MANNITOL, lactose, starch, magnesium stearate, sodium asccharin, Mierocrystalline cellulose, magnesium carbonate and the known standard vector of other industry.Pharmaceutical carrier can be a solid, also can be liquid.
Solid carrier as illustration comprises glucose, carclazyte, sucrose, talcum, gel, agar, pectin, gum arabic, magnesium stearate, stearic acid etc.Solid carrier can comprise that one or more are as seasonings, lubricant, solubilizing agent, suspension agent, filler, glidant, concentrated accessory agent, tamanori, tablet disintegrant; It also can be capsule material.In pulvis, carrier is the solid that exquisiteness is cut apart, and it is the mixture of the activeconstituents cut apart of exquisiteness.In tablet, compound mixes in the proper ratio with the carrier with necessary concentrated characteristic, is densified to desired shape and size.
Liquid vehicle as illustration comprises syrup, peanut oil, sweet oil, water etc.Liquid vehicle is used for obtain solution, suspension, milk sap, syrup and elixir.Synthetics can be dissolved or suspended in pharmaceutically acceptable liquid vehicle, for example water, organic solvent or mix both, or pharmaceutically acceptable oil or fat.Liquid vehicle can contain other pharmaceutically suitable additive, for example solubilizing agent, emulsifying agent, buffer reagent, sanitas, sweeting agent, seasonings, suspension agent, thickening material, staining agent, viscosity modifier and stablizer.
Pharmacy can be adopted multiple mode.If solid carrier, preparation can be made tablet, with the pulvis hard gelatin capsule of packing into, pill, lozenge or medicine sugar.If liquid vehicle, preparation can be made syrup, emulsion or soft gelatin capsule.
Wogonin can supply with the standard system drug package of knowing for people.Correct use Wogonin as medicine or the specification sheets that is used in particular for treating the medicine of anxiety disorder can provide in the lump with packing.
Example:
Extract and purifying wogonin (Wogonin)
Following method can be prepared Wogonin easily in a large number:
Crystallization method
Huang Cengen is worn into powder, the methylene dichloride (DCM) of gained 500g powder with 2L at room temperature squeezed three times.Extract is filtered with the Whatman1 filter paper, in the vacuum extractor of rotation, be concentrated into 200ml in 60 ℃.Filter drying then at the yellow mercury oxide (DCM extract) of bottom with No. 1 filter paper of Whatman.Under refluxing, the 1.5g yellow mercury oxide is dissolved in the 40ml ethanol.Filter this solution and keep room temperature that crystallization is formed.Filter the xln (being needle-like) of Wogonin and with the (see figure 1) of ethanol cleaning.
Behind the crystallization, at first by thiin film chomatography (TLC) (moving phase, DCM: methyl alcohol 10:1) calibrating Wogonin purity, use Vydac C then
18Anti-phase post (150 x 3.9mm) is further determined by HPLC (high performance liquid chromatography) method (HPLC).Moving phase is to be formed with the 3:7 ratio by acetonitrile and water, flows out with the 1:0ml/min turnover rate.Injection volume is 100 μ l, surveys wavelength and is adjusted at 280nm.Used HPLC system comprises a Waters 7120WISP syringe, a DU-65 spectrophotometer, a Waters 600E central controller and Waters 486 adjustable absorbance detectors.
On the TLC plate, observe from the Wogonin ingredients, have only a single mark point.Based on the characteristic of HPLC, when about 95%Wogonin, the purity of assessment ingredients.
Osmose process
Ground sample 100g permeates with methyl alcohol or methylene dichloride.Natural extract obtains from reduction vaporization, does the post chromatographic analysis then on silica gel, uses the chloroform-methanol elution again.
Fractionating process
With the ground sample 100g of ethanol fractionation.Obtain ethanol extraction after under reduction vaporization, removing ethanol.Soluble in water and ethyl ether and n-butanols shake together continuously with this extract.Ethyl ether layer is evaporated to drying.The ethyl ether extract is made column chromatography analysis on silica gel, and uses the chloroform-methanol elution.
Ultrasonic lash method
Ground sample 100g, the solvent of using 2000ml divides three extractions by ultrasonic vibrations 30 minutes.With various extraction solvent: 70% methyl alcohol, methyl alcohol, ethanol, acetoneand ethyl acetate.On silica gel, make column chromatography analysis then, and use the chloroform-methanol elution.
Supercritical fluid extraction (SFE) method
The sample (100g) of pulverizing is put in the sample cartridge of volume 1000ml.With methyl alcohol or 70% methyl alcohol (adding 100ml respectively, 200ml and 300ml) and 2000ml Liquid carbon dioxide as extracting solvent.Extracting temperature is respectively 40,50,60 and 70 ℃.Allow the Liquid carbon dioxide of (200,300 and 400 crust) flows into sample cartridge under the high pressure.When pressure reaches 200,300 and 400 crust, carefully open outlet valve at once, collect solution to the test tube that 1000ml methyl alcohol is housed by pipeline.Leaching process is 10-15 minute, triplicate.Obtain unprocessed extract by reduction vaporization, on silica gel, make column chromatography analysis then, and use the chloroform-methanol elution.
Table 2 extracts the rate of collecting of Wogonin from the root of large-flowered skullcap
| Extraction pattern/solvent | Collect rate mg (Wogonin)/g (the dried root of the root of large-flowered skullcap) |
| Permeate the methanol dichloromethane that spends the night | 2.8 4.0 |
| Fractionation ethanol | 3.2 |
| Ultrasonic vibrations methyl alcohol: water (70:30) methanol | 2.3 2.8 2.7 |
| Supercritical fluid extraction methyl alcohol: water (70:30) methyl alcohol | 2.2 3.7 |
The neuronic electric physiological action of dorsal root ganglion (DRG)
As above described (Hu, et al., Neurosci 77:535-541,1997), prepare 2-3 month big Sprague-Dawley adult rat dorsal root ganglion (DRG) that fresh separated is come out.Cut the rat head, and the spinal segment from the chest to the waist is shredded fast.At once isolate DRG and shift they to contain the Eagle medium that Dulbecco improved (DMEM, Sigma), pH 7.4,349mosmol/L, petri diss in.Remove attachment removal nerve and around after the conjunctive tissue, DRG is shredded, transfer to then in the flask that contains 5ml DMEM, therein Regular Insulin (0.5mg/ml, type III, Sigma), collagen (1mg/ml, type IA, Sigma) and] (0.1mg/ml, type IV Sigma) have dissolved and cultivated in 35 ℃ of water vats that shaking 35-40 minute thymus nucleic acid (Dnase).When cultivation finished, (1.25mg/ml, type II-S Sigma) went to stop by the Regular Insulin lixiviate to add the soybean insulin inhibitor.The neurone (diameter 15-60 μ M) of having isolated is put into the cultivation dish of 35mm, before carrying out electric physiology record, static 30 minutes of minimum maintenance.
With a CEZ-2400 diaphragm/(Nihon Kohden's full cell amplifier Japan), under room temperature (22-25 ℃), notes down to the DRG neurone by patch clamp technique.Gigabit nurse sealing difficult to understand (Gigaohm seal) is made by the borosilicate glass microelectrodes with 2-4 megaohm contact resistance.Unless otherwise indicated, the current potential of film remains on-60Mv usually.Neurone is placed in the extracellular medium, and it contains (in Mm): NaCl 150, KCL 5, CaCl
22.5, MgCl
22,2,4-(2-hydroxy)-1 piperazidine-ethane sulfonic acid (HEPES) 10, D-glucose 10; PH with NaOH transfer to 7.3 and osmolarity transfer to 340mosmol/L with sucrose.Film-pipette is filled the cell internal solvent, comprises (in Mm): CsCl 140, MgCl
22.5, two (oxo nitrilo) tetraacetates (EGTA) 11 of HEPES 10, vinyl, Mg-ATP 5; PH with CsOH transfer to 7.3 and osmolarity transfer to 310mosmol/L with sucrose.(3dB) filtering by probe software and hardware system (Central China University of Science and Technology, Wuhan), stores in laboratory computer and analytical data membrane currents, or by pen register (Nihon Kohden) record at 1KHz.
With gamma-aminobutyric acid (GABA), wogonin (Wogonin) and stable (Diazepam) dissolve in extracellular solvent, the wire pipe array of making via fused quartz tube (external diameter/internal diameter=500/200 μ M) by gravity contacts with these neurones, and silica tube is connected with a series of independently hydraulic accumulators.These pipes are placed in the neurone of these 100 μ M.Neurone is immersed in constantly from the extracellular medium that a pipe flows into, and opens corresponding valve and apply drug solvent, with the horizontal quick travel pipette of micromanipulator.In order to make GABA
AAcceptor recovers from desensitization fully, every dispenser in four minutes once.The galvanograph picture of Fig. 2 shows that Diazepam and Wogonin have strengthened GABA to neuronic effect.Record diagram shows the representational current trace (n=6) of utilizing patch clamp technique to obtain from the DRG neurone.Wogonin has strengthened the GABA-starting current as Diazepam with the same manner.
Pharmacology test
Male ICR mouse (18-23g) arbitrarily is divided into experimental group with them.Only close together with group 4-5, independently ingest and drink water, black circulation of 11 little time and 13 hours.Except that acute deadly vitality test (10 hero or female mice), every experimental group has 16 mouse.
Wogonin and Diazepam are dissolved in the water of pH 10, test that to be concentrated into 10ml/kg before 1 hour oral.For chronic test, mouse is accepted pre-treatment in 5 days before the test.Peritoneal injection (IP) then made with 12.5ml/kg in test before 15 minutes in fluorine horse XiLin (FlumazenilRo15-1788).
The crawler behavior test
The size of ZIL-2 type photoelectricity test case (Beijing medicine university) is 60 X, 60 X 12cm.The circular movable testing cassete of four diameter 25cm is arranged in the casing, have six infrared electro impression probes to be evenly distributed on the sidewall of testing cassete.The number of times of record mouse process infrared electro susceptor in 5 minutes.The increase of the increase response activity behavior of number of times.
The result of table 3 record shows, takes medicine until 30mg/kg, and crawler behavior does not significantly change, and shows no any calming effects.
Table 3
N=16 (every group)
*P＜0.05,
*P＜0.01 obviously is different from control group, the t of Dunnett test after the variance analysis
The test of four orifice plates
The orifice plate instrument be one have circummure around wooden examination chamber (30 centimetres of 60 x, 60 x), 3 centimetres of mutual equidistant holes of four diameters are arranged on the indoor floor.Mouse is placed on the central authorities of chamber.Record is to the number of times of hole probe and the time (File, S.E. and Pellow, S., Br J Pharnacol 86:729-735,1985) of probe stop in five minutes the timed interval.Test is carried out under half-light.Mouse arbitrarily is placed on arbitrary test group and reaches between 8am to 12pm with any order medicine feed.After each test, clean instrument, remove previous footprint trace with paper handkerchief.Activity is is more sought and visited in probe number of times and the increase of residence time reflection.Otherwise, to compare with control group, the minimizing of these parameters shows calm behavior (Nolan N.A. and Parkes, M.W., Psychopharmacol 29:277-288,1973; File S.E. and Wardill, A.G., Psychopharmacol 44:53-59,1975; File S.E. and Pellow, S., Psychopharmacol 88:1-11,1986).
The result of table 3 record shows, takes medicine until 30mg/kg, and mouse is not induced significant calming effects.
The elevated plus-maze test test
Elevated plus-maze test is the planche cross frame by wooden one-tenth, and cantilever (5 centimetres of 25 x) (arm opened in abbreviation) and two cantilevers vis-a-vis (5 centimetres of 25 x) (abbreviation closes arm) that wall is high 20 centimetres of two no barriers are arranged.Cantilever stretches from central platform (5 centimetres of 5 x).Elevated plus-maze test is liftoff 40 centimetres, be placed in the box of 50 centimetres of 30 x, 30 x.Every mouse is placed on the central platform, facing to the cantilever of sealing after four orifice plates that carried out 5 minutes are tested at once.Record enters the number of times of cantilever and is opening arm and closing the time that arm stops in five minutes the timed interval.The sum that enters cantilever is estimated general crawler behavior, and the minimizing of this number shows anxiety.After the experiment, the number of times that enters out arm represents with per-cent that with the sum that enters cantilever the time that enters out the arm stop was also represented with per-cent with the time that enters cantilever (open arm and close arm) stop.Test is carried out under half-light.Mouse arbitrarily is placed on arbitrary test group and reaches between 8am to 12pm with any order medicine feed.After each test, clean instrument, remove previous footprint trace with paper handkerchief.The number of times and the residence time that mouse selects increase to enter out arm then show anxiety effect (Pellow, S., et al., J Neurosci Meth 14:149-167,1985; Lister, R.G., Psychopharmacol 92:180-185,1987).
From entering out arm number of times (acute), show (being summarized in table 4 and Fig. 3) at the per-cent of opening the arm residence time (acute) and the result that enters out arm number of times (chronic), taking medicine 7.5,15 or significant angst resistance effect arranged during 30mg/kg.Fig. 3 represents mouse oral vehicle or medicine, tests in given 5 minutes in elevated plus-maze test, and is acute or chronic after taking medicine 1 hour, test-results.In elevated plus-maze test, enter out the arm number of times or at the average of opening the arm residence time (± standard deviation) percent of total.Do the t-check of Dunnett after variance analysis, the result of the group of taking medicine obviously is different from control group,
*P＜0.05,
*P＜0.01, n=16.
In addition, the angst resistance effect of Wogonin is eliminated fully by benzodiazepine receptors antagonist fluorine horse XiLin (FlumazenilRo15-1788).Fig. 4 represents mouse oral vehicle or medicine, tests in given 5 minutes in elevated plus-maze test, and is acute or chronic after taking medicine 1 hour, test-results.In elevated plus-maze test, enter out the arm number of times or at the average of opening the arm residence time (± standard deviation) percent of total.The angst resistance effect of Wogonin is eliminated (2.5mg/kg) fully by Flumazenil Ro15-1788.Do the t-check of Dunnett after variance analysis, the result of the group of taking medicine obviously is different from control group,
*P＜0.01, n=16.
Table 4
| Medicine (mg/kg) | Sum |
| Acute | |
| Control group | 34.31±1.78 |
| 3.75 | 34.56±0.97 |
| 7.5 | 45.56±1.71 * |
| 15 | 43.50±1.90 * |
| 30 | 47.00±1.93 * |
| Stable 1 | 45.13±2.31 * |
| ± | |
| Chronic | |
| Control group | 25.94±1.94 |
| 3.75 | 27.56±1.90 |
| 7.5 | 31.75±2.07 |
| 15 | 31.56±2.13 |
| 30 | 31.31±1.77 |
| Stable 1 | 29.38±2.67 |
Every group 16 of n=
*The t-check of Dunnett is done in P＜0.01 after the variance analysis
The horizontal metal thread test
The tail of holding mouse lifts mouse, allows it catch the metal wire (diameter 1mm, 15cm is long, from desktop 20cm) of horizontal stretching to decontrol its (Bonetti et al., 1982) then with the forward foot in a step.With the mouse test that can catch metal wire before taking medicine with the rear foot.Write down mouse in ten times, with fore paw or in 3 seconds rear solid end of minimum usefulness can catch the number of times of metal wire effectively.Make medicine of flaccid muscles can damage the ability that mouse catches metal wire, and this is of flaccid muscles and calm relevant.
Wogonin to 30mg/kg is taken in Fig. 5 demonstration, and mouse can be not of flaccid muscles.
Below explained and described the example that the present invention recommended with reference to bibliography, its form and details may change to some extent, but can not depart from category of the present invention (seeing claims).
Claims (2)
1. the purposes of the wogonin with following chemical formula in the medicine of preparation treatment anxiety disorder
2. purposes as claimed in claim 1 is characterized in that, drug prepared is contained in the container, makes a cartridge bag.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2002/000604 WO2004022550A1 (en) | 2002-09-03 | 2002-09-03 | Compound for treatment of anxiety and methods of preparation and use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1671680A CN1671680A (en) | 2005-09-21 |
| CN100491366C true CN100491366C (en) | 2009-05-27 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB02829534XA Expired - Fee Related CN100491366C (en) | 2002-09-03 | 2002-09-03 | Use of wogonin as medicament for treatment of anxiety |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN100491366C (en) |
| AU (1) | AU2002333157A1 (en) |
| WO (1) | WO2004022550A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0402118D0 (en) * | 2004-01-30 | 2004-03-03 | Merck Sharp & Dohme | Polymorphic forms of a GABAA agonist |
| CN100345537C (en) * | 2005-11-09 | 2007-10-31 | 中国药科大学 | Application wogonin for preparing medicine to treat leukaemia |
| CN101091706B (en) * | 2006-06-23 | 2011-05-04 | 和泓生物技术（上海）有限公司 | Excitant of dopamine transport protein and usage |
| WO2015055456A1 (en) * | 2013-10-15 | 2015-04-23 | Unilever Plc | Frozen confection |
| CN108250172A (en) * | 2017-11-22 | 2018-07-06 | 中国科学院西北高原生物研究所 | A kind of compound with antianxiety and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1166358A (en) * | 1997-01-27 | 1997-12-03 | 华中理工大学 | Medicine inhibiting uterine excitation |
| CN1102148C (en) * | 2000-03-03 | 2003-02-26 | 江西江中制药技术中心 | Preparation method of scutellaria root extract |
-
2002
- 2002-09-03 WO PCT/CN2002/000604 patent/WO2004022550A1/en not_active Application Discontinuation
- 2002-09-03 AU AU2002333157A patent/AU2002333157A1/en not_active Abandoned
- 2002-09-03 CN CNB02829534XA patent/CN100491366C/en not_active Expired - Fee Related
Non-Patent Citations (6)
| Title |
|---|
| 5,7-Dihydroxy-8-methoxyflavone from Tetracera india. Leslie J. Harrison等人.Planta Med.,No.60. 1994 |
| 5,7-Dihydroxy-8-methoxyflavone from Tetracera india. Leslie J. Harrison等人.Planta Med.,No.60. 1994 * |
| 半枝莲中二萜内酯和黄酮化合物的分离和鉴定. 朱品业等人.植物资源与环境，第2卷第4期. 1993 |
| 半枝莲中二萜内酯和黄酮化合物的分离和鉴定. 朱品业等人.植物资源与环境，第2卷第4期. 1993 * |
| 山橘的化学成分研究. 沈小玲等人.中国药学杂志，第37卷第1期. 2002 |
| 山橘的化学成分研究. 沈小玲等人.中国药学杂志，第37卷第1期. 2002 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002333157A1 (en) | 2004-03-29 |
| CN1671680A (en) | 2005-09-21 |
| WO2004022550A1 (en) | 2004-03-18 |
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