CN1548053A - New use of baicalin as medicine for treating anxiety neurosis - Google Patents
New use of baicalin as medicine for treating anxiety neurosis Download PDFInfo
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Abstract
The present invention reveals the new medicinal use of baicalin as the effective medicinal components in skullcap root and stem and proposes the application of baicalin compound in treating various anxiety neurosis. It is proved that baicalin taken by mouse in the dosage of 7.5-30 mg/kg has obvious and reliable effect of resisting anxiety neurosis, so that the orally taken dosage for human is calculated to be 0.8-3.5 mg/kg. Baicalin is extracted from skullcap root and stem, has purity not lower than 97 %, and may be prepared into tablet, capsule, dripping pill, oral liquid, injection, etc. The present invention has outstand medicinal effect, low toxicity and low cost.
Description
Technical field
The present invention relates in the Chinese herbal medicine Radix Scutellariae rhizome the new purposes that effective medicinal ingredient baicalin is used to prepare the medicine for the treatment of all kinds of anxiety neurosis diseases.
Background technology
Chinese medicine is thought: Radix Scutellariae (Scutellaria baicalensis Georgi) is the dry root of Labiatae class plant.Cold in nature, bitter in the mouth is returned lung; Gallbladder; Spleen; Large intestine and small intestine meridian.Its medicinal function is a heat clearing and damp drying; Eliminating fire and detoxication; Hemostasis; Antiabortive.The traditional Chinese medical science is used for damp and hot more, fever disease in summer, and vomiting and nausea uncomfortable in chest, damp and hot feeling of fullness, the dysentery jaundice, the cough due to lung-heat, the hyperpyrexia excessive thirst, heat in blood is told nosebleed, carbuncle sore tumefacting virus and frequent fetal movement etc.(Chinese Pharmacopoeia, first nineteen ninety-five, pp.270) modern medicine study proves: the main medicinal ingredient that contains in the Radix Scutellariae rhizome is: baicalin (Baicalin), its content accounts for about the 3-5% of scullcap plant weight, baicalin (Wogonin), its content accounts for about the 0.5-1.3% of scullcap plant weight.
The different name of baicalin is: baicalin, English by name: Baicalin, chemistry is by name: β-D-Glucopyranosiduronic acid, 5,6-dihydroxy-4-oxo-2-phenyl-4H-1 benzopyran-7-yl; Accompanying drawing 1 seen in its chemical structural formula, and molecular formula and molecular weight are: C
21H
18O
11With 446.35, physical behavior is the yellow crystal body, and fusing point is 223-225 ℃, and ultra-violet absorption spectrum is: 242 (4.12); 271 (4.50); 310 (4.22) [Chinese patent medicine quality standard and standard substance research, Chinese medicine science and technology publishing house] (seeing accompanying drawing 2).Its infrared spectrum is seen accompanying drawing 3.
Research at present mainly comprises with the pharmacological action of the relevant baicalin of report:
1. antiinflammatory and anti-allergy action;
2. antibiotic, antivirus action;
3. hepatic cholagogic effect;
4. antihypertensive diuretic effect;
5. to central nervous system's sedation;
6. refrigeration function;
7. spasmolytic and antioxidation;
8. to the therapeutical effect of diabetic;
9. to cardiovascular effect and the effect that brings high blood pressure down;
10. the effect of fat and cholesterol in the reduction blood.
[Chinese medicine modern study and application, Volume Four: pp.3943-3977; Modern Chinese medicine library editorial board edits, and the Xueyuan Press publishes].
Up to now, Chang Yong anti anxiety agent thing mostly is the chemical constituent medicine clinically, as: nitrodiazepam; Mexazolam; Flutazolam; Etizolam and Etifoxine Hydrochloride etc.[wear spedex: the special medicine handbook of practical new drug, pp.424-434; The People's Medical Officer Press publishes] such medicine all has stronger central nerve inhibition effect, and can produce the drug dependence effect, take in a large number for a long time will produce that more serious nerve suppresses and side effect such as drug dependence.Domestic and foreign literature is not seen the research report of relevant baicalin to the drug action of all kinds of anxiety disease as yet at present.Also do not see clinically and contain the treatment that baicalin is main medicinal raw material, control and alleviate the medicine and the preparation of all kinds of anxiety symptoms.
Summary of the invention
The purpose of this invention is to provide a kind of low toxicity, low drug side effect, the medicine source is abundant, and can effectively treat and alleviate the new anti anxiety agent thing of all kinds of anxiety neurosis patient symptoms.
The baicalin chemical compound is a main medicinal ingredient in the Chinese herbal medicine Radix Scutellariae rhizome.Experimental results show that: baicalin can combine with gamma-aminobutyric acid receptor in the cerebral tissue (GABA receptor) functional site is competitive, regulates the central nervous system function disorder, thus the drug action that reaches treatment and alleviate all kinds of anxiety neurosis symptoms.At present, the GABA receptor is considered to a kind of main inhibiting aminoacid conductor that rises in mammiferous central nervous system.GABA transmits its many information activity [Tallman by the GABA receptor that is confined to cyton and teleneuron, JF.Gallager, DW.1985.The GABA-ergic system:a locus ofbenzodiazepine action.Annu Rev Neurosci.; 8:21-44).Document is pointed out: the GABA receptor has many functional activation scopes and ion channel and benzene phenodiazine (BDZ), barbiturate in the human brain; The binding site of cocculin and anesthesia steroid, [Smith, GB.Olsen, RW.1995.Trends Pharmacol Sci.16 (5): 162-8]; [Pritchett, DB.1989..Nature; 338 (6216): 582-5].
Benzene phenodiazine (BDZ) kind comprises first phenodiazine (stabilizing); Trizzolam and flunitrazepam.In mammalian central nervous system, the main behavioral function and the anxiety of traditional benzene phenodiazine, convulsion, calm relevant with the muscular flaccidity effect.The chemistry medicine is stable, nitrodiazepam, and trizolam and benzene first phenodiazine are GABA receptor competition bound substances, and this compounds is emulative to be combined with GABA receptor function corresponding site, thereby effectively blocks anxiety, the release of relevant transmitter substances such as convulsions.
Baicalin does not as yet see both at home and abroad at present that as the pharmacy notion of anti anxiety agent report is arranged.But, the a large amount of of the inventor exsomatize and the confirmation of whole pharmacodynamics experimental studies results: this Chinese medicine monomer chemical compound has and the competitive bonded effect of GABA receptor BDZ functional site, be a kind of analeptic of GABA receptor BDZ function binding site, have tangible anxiety and abirritative drug effect.
Baicalin as antianxiety drugs and other chemical constituent antianxiety drugs relatively, characteristics such as it is low to have toxicity, and side effect is little after the medication.The lethal dose of mouse subcutaneous injection baicalin is 6g/kg; The LD of mouse peritoneal injection baicalin
50Dosage is the precious Kui of 3.081g/kg[king etc.: Chinese Hospitals pharmaceutical journal 1993; 13 (8) 354-355], [woods Ji Qiang etc.: Journal of physiology, 1958; 22 (3) 249]; [the rugged equality of Bears: medical central magazine, 1959; 145:907].The oral baicalin LD of mice that the inventor measures
50Dosage is 8.937 ± 1.146g/kg.
Baicalin toxicity is very low, there are not tangible central nervous system's inhibitory action and myorelaxant effects, in effective antianxiety drug weight range, can avoid the caused central nerve inhibition effect of other chemical constituent anti anxiety agent thing, be a kind of safe and reliable, the new drug of the anxiety disease that can take for a long time.
The zoopery result shows before clinical: the oral baicalin anxiety of mice optimum medicine efficacy dosage range is 7～30mg/kg/ time.According to the common method of drug dose design, the per weight effective dosage ranges of calculating the human oral baicalin is greatly about about 0.8～3.5mg/kg/ time.And, according to the weight of patient anxiety symptom, and the elimination situation of the back anxiety symptom of taking medicine, oral one to three time of every day can be selected.
When during as the medicine of anxiety disease, making various dosage forms, for example with baicalin as main medicinal ingredient with baicalin: tablet, capsule, drop pill, oral liquid, and injection etc.
Description of drawings
Fig. 1 is the molecular structural formula of baicalin;
Fig. 2 is the scintigram of baicalin absorbance;
Fig. 3 is the infrared spectrogram of baicalin;
Fig. 4 is baicalin and GABA receptor competition knot, and 50% suppresses stable in conjunction with concentration (IC
50) curve.
The specific embodiment
One. gamma-aminobutyric acid receptor (GABA) is competitive in conjunction with the baicalin measurement result:
It is stable in conjunction with concentration (IC in GABA receptor competition inhibition 50% that the competitive associated methods of application of radiation immunity is measured coumpound baicalin
50) and the stable binding constant (K of competitive inhibition
i).
Experiment adopts the Mus brain cell that exsomatizes through extract at low temperature and purification Mus cranial nerve GABA receptor protein.[N-methyl-3H] Flunitrazepam that employing is provided by Amersham Phamacia Biotech UK Limited, as the baicalin chemical compound of immune marker and purity＞98% as the competition conjugate.Use competitive in conjunction with radioimmunoassay method (Viola, H.1999 BiochemBiophys Res Commun.262 (3): 643-6); [Villar, HO.1989.Mol Pharmacol.36 (4): 589-600] and [Lelas, S.1999.Behav Pharmacol 10 (1): 39-50] measures IC
50And K
i
Measurement result shows as shown in Figure 4:
Baicalin IC
50Be 137.07 ± 8.50uM
K
iBe 77.10 ± 4.79uM
About baicalin is the blank spot in this area research in the past to 50% competition in GABA receptor BDZ site in conjunction with the data of inhibition concentration and competition inhibition constant and conclusion.Baicalin provides the up-to-date empirical theory foundation of this effective ingredient as all kinds of anxiety diseases of treatment to the research conclusion of GABA receptor 50% competitive inhibition concentration and inhibition constant.
Two. oral various dose baicalin mouse anti anxiety drug action animal experimental observation
Adopt the secondary Kunming mouse; Male; Body weight 16-18g.Provide by Academy of Medical Sciences Experimental Animal Center.The quality certification number: capital moving pipe word 200201, the secondary Animal House is conventional raises.Animal House temperature: 24 ± 2 ℃; Humidity: 60%; Light application time: 12 hours.
Be subjected to the reagent thing:
1) baicalin (Baicalin) dark-brown powder; Mildly bitter flavor, poor solubility in aqueous solvent, normal temperature drying is preserved; Purity＞98.6%.
2) nitrodiazepam: as positive control drug, white tablet; Specification: the 5mg/ sheet, commercial.This medicine poor solubility in aqueous solvent.
Laboratory animal is established high dose group (30mg/kg) at random; Middle dosage group (15mg/kg) and low dose group (7.5mg/kg).Other establishes known positive drug nitrodiazepam matched group (1mg/kg); With normal blank group.
All kinds of reagent things that are subjected to are prepared with the distilled water dissolving by per weight dosage, adopt and irritate the administration of stomach method.The administration volume is 0.5ml.Irritate behind the stomach and to begin every pointer in 60 minutes and measure.
Experimental facilities:
1) overhead cross platform labyrinth: cross platform labyrinth is by the plank self-control of diameter 0.5cm, and its bottom shape is cruciform shape, is divided into four districts, i.e. two symmetric open zones, and its bottom area is 25 * 5cm; Two symmetric enclosed areas, its bottom area are 25 * 25cm, and this district's periphery is surrounded sealing by the plank of high 10cm.Center, junction, four districts area is 5 * 5cm.This device is positioned on the support of the 40cm that is above the ground level.In the test test mice is put into the center, write down time and number of times that experimental animal in 300 seconds enters open zone or enclosed area simultaneously.
Experimental record method: when the experiment mice health enters open zone or enclosed area, write down the number of times that this animal enters in this district and the time of stop.[Pellow，S.1986.Anxiolytic?andanxiogenic?drug?effects?on?exploratory?activity?in?an?elevated?plus-maze：anovel?test?of?anxiety?in?the?rat.Pharmacology.Biochenistry?and?Behavior?24(3)：525-529)]。Experiment mice selects to enter open zone number of times and the degree that how much shows medicine anxiety effect that is trapped in the open zone time.
2) four hole casees: four hole casees are the wood-block self-control of 0.5cm by thickness.Its casing specification is 60 * 60 * 30cm.Box bottom has the circular hole of four diameter 4cm apart from four jiaos of 5cm places.Casing is lifted placement apart from ground 50cm place, during on-test experimental animal is put into case center, four holes, allows experimental animal free movable in casing.Write down simultaneously test mice in 300 seconds in four hole casees probe and the number of times of perpendicular body.
The experimental record method: when test mice nose during to eye socket lower edge contact circular hole edge, record test mice probe once; When the two front foot built on stilts of test mice, the perpendicular body of record mice once.[File，SE.1985.The?effects?of?trizolobenzodiapines?in?two?animal?tests?ofanxiety?and?in?the?holeboard.British?Journal?of?Pharmacology.86(3)：729-735]。With normal blank treated animal relatively, the treated animal of taking medicine probe and the minimizing degree of erecting the body number of times reflect the height of its calm behavior.
3) horizontally suspend rack device: with diameter 1mm, the cotton rope of long 20cm is fixed on the position that is higher than desktop 20cm.In the test, the fore paw of test mice is caught cotton rope, loose one's grip then, allow animal be suspended on the cotton rope.Write down the number of times that falls from cotton rope in the test mice 60 seconds simultaneously.[Bonetti, EP.1982 Psychopharmacology (Berl.) .78 (1): 8-18], the mice of taking medicine is from the fall strong and weak degree of number of times reflection experiment mice muscular strength of suspension rope.
Above-mentioned experimental facilities is fixed in the laboratory, makes every effort to quiet after the experiment beginning, avoids noise and other interference factor to influence experimental result as far as possible.
Be interpreted as with the relevant document that the animal testing behavior changes about anxiety: normal mouse would rather be selected to enter the enclosed area in labyrinth and not select the open zone to be because fear is high in overhead cross maze test model, it is reluctant in the narrow relatively active reason in scaoffold open zone is to be difficult for keeping balance in open height space, easily produces the misgivings that worry falls down.Event thinks that what and the length in the open zone time of staying of mice movable number of times in the open zone reflect that experiment mice is worried and the power of generation misgivings degree.Experiment mice is popped one's head in four hole casees and liftoff with the number of times that keeps body erect what of forelimb, then reflects the power of anxiety and dry moving behavior in the experiment mice experiment.Calm mice is popped one's head in four hole casees and perpendicular body number of times obviously is less than the dry moving mice of anxiety.
All experimental data adopts average ± standard deviation (X ± S) expression.Adopt T check and x
2Check is organized a statistics relatively to each group data.
(1) each dosage group mice general pharmacology is learned the observed result that changes behind the oral baicalin
Ordinary circumstance and normal control treated animal were not seen obvious change, activity, muscular strength after each dosage treated animal was taken medicine; Spirit nervous system and the no abnormal discovery of respiratory circulatory system, the animal of all taking medicine does not have death.
(2) each dosage group mice enters open zone and the comparison of enclosed area number of times behind the oral baicalin
Experiment mice enters open zone, cross platform labyrinth and enclosed area in the table 1. 300 seconds
Number of times and percentage comparisons
Enclosed area, total degree open zone
Group (inferior/300 second) % several % of number of times
High dose group 22.42 ± 2.78 10.33 ± 2.27
*46.21 ± 6.17
*12.00 ± 1.35 53.79 ± 6.17
Middle dosage group 25.83 ± 2.59 12.33 ± 1.88
*47.66 ± 4.21
*13.67 ± 1.50 52.09 ± 4.52
Low dose group 23.00 ± 2.89 9.92 ± 1.49 43.08 ± 2.68
*13.08 ± 1.68 56.93 ± 2.68
Stable group 30.33 ± 3.34
*15.50 ± 3.07
*51.06 ± 3.03
*14.83 ± 1.75 48.12 ± 3.12
Normal control group 25.67 ± 4.89 8.33 ± 1.76 33.64 ± 5.80 17.33 ± 3.77 66.36 ± 5.80
Compare with the normal control group: *
p＜0.05;
*P＜0.01
(3) each dosage group mice enters open zone and enclosed area time ratio behind the oral baicalin
Experiment mice enters open zone, cross platform labyrinth and enclosed area in the table 2. 300 seconds
Time and percentage comparisons
The enclosed area, open zone
% time group time (second) (second) %
High dose group 8.25 ± 12.20
*26.09 ± 4.07
*213.00 ± 12.14 70.82 ± 3.77
Middle dosage group 84.92 ± 12.15
*28.31 ± 4.05
*214.92 ± 14.16 71.64 ± 4.71
Low dose group 72.08 ± 11.29
*24.05 ± 3.71
*216.42 ± 17.86 72.13 ± 5.94
Stable group 91.67 ± 13.37
*30.55 ± 4.44
*199.08 ± 11.63 66.33 ± 3.89
Normal control group 53.25 ± 9.57 17.75 ± 3.19 238.42 ± 11.91 79.47 ± 3.98
Compare with the normal control group:
*P＜0.05;
*P＜0.01
(4) each dosage group mice probe behind the oral baicalin; The perpendicular body and the number of times that falls are relatively
Experiment mice probe in the table 3. 300 seconds; The perpendicular body and the number of times that falls are relatively
The perpendicular body number of times of the group probe number of times baicalin number of times that falls
High dose group 9.00 ± 3.41 16.00 ± 3.84
*0.58 ± 0.99
Middle dosage group 17.58 ± 3.45
*19.17 ± 4.45
*0.42 ± 0.67
Low dose group 18.67 ± 4.80 17.67 ± 4.79
*0.58 ± 0.79
Stable group 10.67 ± 3.70 10.75 ± 2.56
*0.42 ± 0.67
Normal control group 19.42 ± 4.93 23.66 ± 4.48 0.25 ± 0.45
Compare with the normal control group:
*P＜0.05;
From table 1-3 experimental result as seen:
1. each dosage group mice of oral baicalin enters the open zone number of times and enters open zone number of times percentage rate in high platform cross labyrinth all obviously increase than normal blank group, wherein increases the most obvious with middle dosage group (15mg/kg).After taking medicine, three dosage groups enter relatively no significant difference of closed side number of times and percentage rate and normal blank group data.
2. each dosage group mice of oral baicalin enters the open zone time and enters open zone time percentage rate and all more also is significantly increased than normal blank group data in high platform cross labyrinth, wherein obvious with high dose group (30mg/kg) and middle dosage group (15mg/kg) increase, p＜0.01.After taking medicine, three dosage groups enter relatively no significant difference of closed side time and percentage rate and normal blank group data, p＞0.05.
3. each dosage group mice of oral baicalin test result in four hole casees shows each dosage group (7.5-30mg/kg) mice probe and erects the body number of times and the normal control group relatively has notable difference, p＜0.05.
4. each dosage group mice of oral baicalin all finds no drug-induced phenomenon of flaccid muscles.
Above-mentioned experimental result shows: oral baicalin (Baicalin) can obviously change the behavior characteristics of mice on test set of taking medicine, mainly show as and enter high platform cross labyrinth open zone number of times and holdup time and percentage rate and all obviously increase than normal matched group, probe and perpendicular body number of times reduce in four hole casees.Above-mentioned experimental result confirms that baicalin has calm and drug action antianxity, and this medicine does not have obvious influence to the nervous system and the muscular strength of laboratory animal.
Claims (3)
1. one kind is adopted baicalin (Baicalin) as main medicine, treats the new purposes of all kinds of anxiety diseases.
2. employing baicalin according to claim 1 is treated the new purposes of all kinds of anxiety diseases, it is characterized in that, the oral effective dose of human body per weight is 0.8-3.5mg/kg.
3. employing baicalin according to claim 1 is treated the new purposes of all kinds of anxiety diseases, it is characterized in that, with baicalin as the dosage form of anti anxiety agent thing is: tablet, capsule, drop pill, oral liquid and injection etc.
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|---|---|---|---|
| CNA031365566A CN1548053A (en) | 2003-05-23 | 2003-05-23 | New use of baicalin as medicine for treating anxiety neurosis |
| PCT/CN2004/000470 WO2004103386A1 (en) | 2003-05-23 | 2004-05-12 | New use of baicalin for treating anxiety |
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|---|---|---|---|
| CNA031365566A CN1548053A (en) | 2003-05-23 | 2003-05-23 | New use of baicalin as medicine for treating anxiety neurosis |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190057782A (en) * | 2017-11-20 | 2019-05-29 | 종근당건강 주식회사 | Composition for improving sleep disorder containing lettuce and Scutellariae extract as an active ingredient |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8334310B2 (en) | 2006-08-31 | 2012-12-18 | Simon Fraser University | Selective glycosidase inhibitors and uses thereof |
| LT2655388T (en) | 2010-12-23 | 2016-11-10 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| WO2012129651A1 (en) | 2011-03-31 | 2012-10-04 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| EP2726492B1 (en) | 2011-06-27 | 2017-11-01 | Alectos Therapeutics Inc. | Selective glycosidase inhibitors and uses thereof |
| WO2014032188A1 (en) | 2012-08-31 | 2014-03-06 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
| EP2890676B1 (en) | 2012-08-31 | 2018-12-05 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
| AU2013337570B2 (en) | 2012-10-31 | 2018-01-18 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
| CN114634538B9 (en) * | 2022-03-25 | 2024-05-03 | 杭州佳嘉乐生物技术有限公司 | Method for extracting baicalin from dilute brine under positive and negative pressure |
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- 2003-05-23 CN CNA031365566A patent/CN1548053A/en active Pending
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190057782A (en) * | 2017-11-20 | 2019-05-29 | 종근당건강 주식회사 | Composition for improving sleep disorder containing lettuce and Scutellariae extract as an active ingredient |
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