CN1723990A - Compound Chinese patent drug - Google Patents
Compound Chinese patent drug Download PDFInfo
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- CN1723990A CN1723990A CN 200410069787 CN200410069787A CN1723990A CN 1723990 A CN1723990 A CN 1723990A CN 200410069787 CN200410069787 CN 200410069787 CN 200410069787 A CN200410069787 A CN 200410069787A CN 1723990 A CN1723990 A CN 1723990A
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- 229940079593 drug Drugs 0.000 title claims description 110
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- 240000001341 Reynoutria japonica Species 0.000 claims abstract description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 15
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- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A Chinese patent medicine 'ErHuHuanTeng' in the form of tablet, capsule, or dropping pill for preventing and treating dysophoria is prepared from bupleurum root, corydalis tuber, albizia flower and fleece flower stem.
Description
Technical field
The present invention relates to be used for the treatment of the compound Chinese patent medicine " Chinese patent drug " of all kinds of anxiety neurosis.
Background technology
Chinese medicine thinks that the property of medicine of Radix Bupleuri (Radix Bupleuri) is: hardship, be slightly cold, and return liver, gallbladder meridian.Its effect is a reconciling superficies and interior, and is soothing the liver, yang invigorating.Can be used for the treatment flu, heating, alternate attack of chill and fever, distending pain in the chest and hypochondrium, menoxenia, uterine prolapse, proctoptosis etc.
The property of medicine of Rhizoma Corydalis (Rhizoma corydalis) is: hot, bitter, warm, return liver, spleen channel.Its effect is to invigorate blood circulation, promoting the circulation of QI, pain relieving.Can be used for treating the breast side of body, epigastric pain, amenorrhea, dysmenorrhea, postpartum stagnation, tumbling and swelling.
The property of medicine of Flos Albiziae (Flos Albiziae) is: sweet, flat.GUIXIN, Liver Channel.Its effect is a resolving stagnation for tranquilization.Can be used for treating irritability, melancholy insomnia.
The property of medicine of Caulis Polygoni Multiflori (Caulis Polygoni Multiflori) is: sweet, flat.GUIXIN, Liver Channel.Its effect is a nourishing blood to tranquillize the mind, dispelling wind and removing obstruction in the collateral.Can be used for the Cure for insomnia dreaminess, blood deficiency void, last general pain, rheumatic arthralgia.
(see Chinese Pharmacopoeia, first one, 2000, pp.232; 108; 218; 112)
The traditional Chinese medical science it is generally acknowledged that anxiety is owing to visceral dysfunction, irritability stasis, lack of preservation of spirit and qi-blood disharmony causing.Clinically be characterized by dreaminess, vexed, bitter taste, constipation, uncomfortable in chest etc.
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. [are worn spedex: the special medicine handbook of practical new drug, pp.424-434; The People's Medical Officer Press publishes].Such medicine all has the effect of stronger inhibition nervus centralis, and can produce drug dependence, takes in a large number for a long time, can produce side effect such as more serious nerve inhibition and drug dependence.
Summary of the invention
The objective of the invention is development and provide a kind of low toxicity, low drug side effect, medicine source to enrich, and can effectively treat and alleviate the new anxiety disease Chinese patent medicine of all kinds of anxiety neurosis patient symptoms.
" Chinese patent drug " is by above-mentioned four flavor Chinese medicines: Radix Bupleuri, Rhizoma Corydalis, Flos Albiziae fleece-flower root rattan mix with special ratios.Its sweet in the mouth, little hardship, property are put down, and main formula wherein adopts Radix Bupleuri, brings into play its depressed liver-energy dispersing and QI regulating, the resolving depression of calming the nerves, the effect of conditioning viscera.Add the Rhizoma Corydalis of promoting flow of QI and blood, be equipped with and support Caulis Polygoni Multiflori and the Flos Albiziae that brain is calmed the nerves, make being so incensed that of quietness, thereby reach the effect of mind tranquilizing and the heart calming with rising.
In " Chinese patent drug " this Chinese patent medicine, the weight of various Chinese herbal medicine (weight of said Chinese herbal medicine in this description all refers to the weight when Chinese herbal medicine is that dry back is sold in the Chinese medicine shop) ratio can be in following scope: Radix Bupleuri 25.80～38.70%; Rhizoma Corydalis 18.00～27.00%; Caulis Polygoni Multiflori 18.00～27.00%; Flos Albiziae 18.00～27.00%.
The optimum weight ratio of the various compositions of " Chinese patent drug " is:
Radix Bupleuri 32.50%; Rhizoma Corydalis 22.50%; Caulis Polygoni Multiflori 22.50%; Flos Albiziae 22.50%.
With above-mentioned Chinese patent medicine " Chinese patent drug " when making tablet, capsule, pill, an amount of cellulose can be added wherein, so that medicine is shaped.
When above-mentioned Chinese patent medicine " Chinese patent drug " is made oral liquid or injection, then in its extract, add an amount of distilled water.
" Chinese patent drug " is the compound Chinese patent medicine that is mixed with special ratios by above-mentioned four flavor bupleurum Chineses, Rhizoma Corydalis, Caulis Polygoni Multiflori and Flos Albiziae.Experimental results show that: " Chinese patent drug " 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.The GABA-ergic system:a locus ofbenzodiazepine action.Annu Rev Neurosci.1985; 8:21-44].Document is pointed out: the GABA receptor has many functional activation scopes and ion channel and benzene phenodiazine (BDZ) in the human brain, barbiturate, binding site [Smith, GB.Olsen, the RW.Trends Pharmacol Sci.1995 of cocculin and anesthesia steroid; 16 (5): 162-8]; [Pritchett, DB.Nature 1989; 338 (6216): 582-5].
Benzene phenodiazine kind comprises stable (diazepam), triazolam (trizolam) and flunitrazepan (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.Chemical drugs is stable, nitrodiazepam, triazolam and benzene first phenodiazine are GABA receptor competition bound substances, this compounds combines with GABA receptor function corresponding site competitively, thereby effectively blocks anxiety, the release of relevant transmitter substance such as convulsions.
Chinese patent medicine as " Chinese patent drug " does not as yet see both at home and abroad at present that as the pharmacy notion of anti anxiety agent report is arranged.The inventor exsomatizes and the confirmation of whole pharmacodynamics experimental studies results from a large amount of: this Chinese patent medicine 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 drug effect characteristic antianxity.
" Chinese patent drug " 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 oral median lethal dose(LD 50) of " Chinese patent drug " mice is 7.145 ± 1.155g/kg.This illustrates that its toxicity is very low, and experimental results show that no 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.
Description of drawings
Fig. 1 is " Chinese patent drug " capsule 50% stable dosage (IC that suppresses
50) and the 50% stable constant (K that suppresses
i) graph of relation.
The specific embodiment
The present invention infers the anxiety effect of Chinese patent medicine " Chinese patent drug " from analyzing following experimental result.
One. gamma-aminobutyric acid receptor (GABA) is competitive to be measured in conjunction with " Chinese patent drug ":
The competitive associated methods of application of radiation immunity, it is stable in conjunction with concentration (IC in GABA receptor competition inhibition 50% to measure " Chinese patent drug "
50) and the stable binding constant (K of competitive inhibition
i).
1. be subjected to reagent thing preparation method:
It is good that vinegar is carried " Chinese patent drug " capsule active drug composition dissolubility in water.The room temperature lucifuge is moistureproof preserves." Chinese patent drug " capsule extract is measured gradient concentration by difference be dissolved in 50mM Tris, in the pH7 buffer.Add DMSO, final concentration is 10%.
2.GABA receptor membrane protein preparation method:
Extract ICR mouse brain tissue rapidly, in low temperature 10mM Tris buffer, clean the back and in-80 ℃ of cryogenic refrigerators, store for future use.Murine brain is put into low temperature 0.32M sucrose solution (20ml/g tissue).Prepare murine brain homogenate with Potter-Elvehjem Tissue Grinders at low temperatures.Murine brain homogenate was descended centrifugal 10 minutes at 4 ℃ of 1000g (3000rpm), collect supernatant centrifugal 20 minutes of 4 ℃ of 20000g, collect the centrifugation memebrane protein, use 50mM Tris-Cl, the pH7.4 buffer is stored in-80 ℃ of refrigerators standby by 0.8-1.6mg/ml concentration suspension Mus meninges albumen.
3.
3H-flunitazepam suppresses in conjunction with measuring:
Add 4 μ l～1mg/ml Mus meninges albumen in the drug level by different mensuration; 1nM[
3H]-flunitazepam, total molten amount is 200 μ l.Non-specific binding adopts 20mM stable.Sample is put into the frozen water reaction and is adsorbed binding film albumen with Whatman GF/B filters filter paper sucking filtration after 90 minutes.Whatman GF/B filters filter paper dodges monitor record medicine in conjunction with the CPM number with liquid after the rinsing in 4ml scintillationcocktail liquid.Adopt following computing formula to calculate " Chinese patent drug " capsule 50% stable constant (K that suppresses
I) and the 50% stable dosage (IC that suppresses
50).
Measuring result: (see figure 1)
" Chinese patent drug " capsule 50% stable dosage (IC that suppresses
50): 70.12ng/ml.
" Chinese patent drug " capsule 50% stable constant (K that suppresses
i): 35.10ng/ml.
" Chinese patent drug " provides the 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 " Chinese patent drug " is to the laboratory observation of mouse anti anxiety drug action
1 animal:
Adopt the ICR mice; Male; Body weight 16-18g.Raise in the conventional animal room.Animal House temperature: 24 ± 2 ℃; Humidity: 60%; Light application time: 12 hours.
2. be subjected to the reagent thing:
1) " Chinese patent drug " capsule, the dark-brown powder; Be that 5% acetic acid water preparation extracts composition, dissolubility is good in water, and normal temperature drying keeps in Dark Place.
2) chemical medicine is stable: white powder; Commercial.Provide by the Sigma chemical company.This chemical compound poor solubility in aqueous solvent.
3. test is divided into groups and dosage:
Laboratory animal is established " Chinese patent drug " capsule in high dose group (62.5mg/kg) at random; Dosage group (31.3mg/kg) and " Chinese patent drug " capsule low dose group (15.7mg/kg) in " Chinese patent drug " capsule.Other establishes known positive drug nitrodiazepam matched group (1mg/kg); With the blank group.Every group of 10 mices.
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.Every mice administration volume is 0.2ml, and in experiment beginning administration in preceding 60 minutes, the normal control group is pressed the equal-volume distilled water and irritated stomach.Irritate behind the stomach and to begin every index determining in 60 minutes.
4. experimental facilities:
(1) cross platform labyrinth: cross platform labyrinth is by the self-control of the plank 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.
(2) four hole casees: four hole casees are by the wood-block self-control of diameter 0.5cm.Its casing specification is 60 * 60 * 30cm.Box bottom has the circular hole of four diameter 4cm apart from four jiaos of 5cm places.During on-test experimental animal is put into case center, four holes, allow 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 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 mice, the perpendicular body of record mice once.
[see File, SE.The effects of trizolobenzodiapines in two animaltests of anxiety and in the holeboard.British Journal of Pharmacology1985; 86 (3): P.729-735]
(3) the optoelectronic induction activity is measured the case hanger bracket: by four diameter 25cm, the transparent round tank of high 15cm is formed, equal portions are fixed 6 optoelectronic induction probes on the bucket wall, when experiment mice is movable in bucket, optoelectronic induction probe automatically the record mice through the number of times of optoelectronic induction probe, 300 seconds minutes of computer control record and movable number of times.
Above-mentioned experimental facilities is put into fixedly laboratory, makes every effort to quiet after the experiment beginning, avoids noise and other interference factor to influence experimental result as far as possible.
5. observation index:
1) the activity photoelectric recording number of times of mice in active box in 300 seconds.
2) mice enters high platform cross platform labyrinth open sides number of times and percentage rate in 300 seconds.
3) mice enters high platform cross platform labyrinth closed side number of times and percentage rate in 300 seconds.
4) mice enters cross platform labyrinth open sides total time and percentage rate in 300 seconds.
5) the mice number of times of in four hole casees, popping one's head in 300 seconds.
6) mice perpendicular body number of times in four hole casees in 300 seconds
6. statistical analysis:
All experimental data adopts average number ± standard deviation (X ± S) expression.Adopt T check and X
2Check is organized a statistics relatively to each group data.
7. experimental result:
1) each dosage group mice general pharmacology is learned the observed result that changes behind oral " Chinese patent drug " capsule:
Ordinary circumstance and blank 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 sides/closed side number of times observed result behind oral " Chinese patent drug " capsule
Experiment mice enters cross platform labyrinth open sides/closed side number of times and percentage comparisons (n=10) in the table 1. 300 seconds
| Group | Total degree (inferior/300 second) | Open sides | The closed side | ||
| Number of times | ％ | Number of times | ％ | ||
| Dosage group low dose group tranquilizer group blank group in the high dose group | 23.5±2.64 22.7±2.75 22.4±3.98 20.1±3.48 20.0±4.92 | 9.5±1.51 * 10.0±1.41 ** 8.1±1.59 * 9.68±2.12 ** 4.4±1.43 | 40.50±3.65 ** 44.23±2.87 ** 36.89±3.67 ** 48.05±6.48 ** 22.02±4.65 | 14.0±1.56 12.7±1.57 * 14.3±2.71 10.5±2.12 * 15.6±3.92 | 59.10±3.65 * 55.77±2.87 * 63.11±3.67 51.95±6.48 * 77.98±4.65 |
Compare with the blank group:
*P＜0.05;
*P＜0.01
3) each dosage group mice enters open sides/closed side time observation behind oral " Chinese patent drug " capsule
Experiment mice enters cross platform labyrinth open sides/closed side time and percentage comparisons (n=10) in the table 2. 300 seconds
| Group | Open sides | The closed side | ||
| Time (second) | ％ | Time (second) | ％ | |
| Dosage group low dose group tranquilizer group blank group in the high dose group | 54.0±9.27 ** 9.5±7.57 ** 7.0±10.88 ** 72.3±12.59 ** 31.7±8.01 | 18.80±3.30 ** 20.80±2.54 ** 16.21±3.76 ** 25.04±4.06 ** 11.03±2.68 | 233.4±11.55 * 226.3±7.12 * 243.0±12.32 215.9±10.63 * 255.4±7.78 | 81.20±3.30 79.20±2.54 83.79±3.76 74.96±4.06 * 88.97±2.68 |
Compare with the blank group:
*P＜0.05;
*P＜0.01
4) perpendicular body number of times of each dosage group mice probe and activity change behind oral " Chinese patent drug " capsule
Experiment mice probe in the table 3. 300 seconds, perpendicular body number of times and activity change relatively (n=10)
| Dosage group low dose group tranquilizer group blank group in the group high dose group | The perpendicular body number of times of total probe | The probe number of times | Perpendicular body number of times | The activity number of times |
| 38.6±4.77 39.3±3.62 * 42.3±7.41 * 43.8±7.35 ** 37.1±4.43 | 19.0±5.46 * 20.5±4.33 ** 21.6±5.58 ** 23.9±3.98 ** 17.4±2,54 | 19.6±3.72 ** 18.5±2.72 ** 20.7±5.08 ** 19.9±4.41 ** 29.7±3.40 | 281.5±20.54 307.0±28.76 243.0±12.32 283.5±31.94 298.7±42.90 |
Compare with the blank group:
*P＜0.05;
*P＜0.01
From the table 1-3 experimental result as seen:
1) oral each dosage " Chinese patent drug " capsule mice enters the open sides number of times in high platform cross labyrinth all obviously increases than normal blank group with the percentage rate that enters the closed side number of times, wherein increases the most obvious with dosage group (31.3mg/kg) in oral " Chinese patent drug " capsule.But three dosage treated animals of " Chinese patent drug " capsule enter the open sides number of times and percentage rate does not all surpass stable matched group level.After taking medicine, outer other treated animal of " Chinese patent drug " Capsules group animal a good appetite suddenly appearing in a serious disease dosage group enters relatively no significant difference of closed side number of times and percentage rate and blank group data.
2) oral each dosage group " Chinese patent drug " capsule mice enters the open sides time and enters the percentage rate of open sides time and all is significantly increased than blank group data in high platform cross labyrinth, wherein obvious with dosage group (31.3mg/kg) and high dose group (62.5mg/kg) increase in oral " Chinese patent drug " capsule, p＜0.01.But three dosage treated animals of oral " Chinese patent drug " capsule enter the open sides time and percentage rate does not surpass tranquilizer matched group level." Chinese patent drug " capsule in high dose group and middle dosage treated animal are detained closed side time and percentage rate and blank group data relatively, p＜0.05.
3) each dosage group mice of oral " Chinese patent drug " capsule test result in four hole casees shows, total probe of each dosage treated animal of oral " Chinese patent drug " capsule and perpendicular body number of times are apparently higher than blank group level.Wherein mice is popped one's head in number of times apparently higher than the blank group, and (p＞0.05), and the perpendicular body number of times of each dosage treated animal obviously reduces (p＜0.05) than the blank group.
4) each dosage group mice of oral " Chinese patent drug " capsule all finds no drug-induced activity significant change phenomenon, and animal activity quantitative determination and the blank group of taking medicine be no significant difference relatively all.
8. conclusion:
Chinese patent medicine " Chinese patent drug " capsule can obviously change the behavioral trait of experiment mice on test set, mainly show as and enter high platform cross labyrinth open sides number of times, be detained the open sides time and percentage rate separately all increases than the blank group, oral " Chinese patent drug " capsule animal probe number of times and the apparent in view increase of blank group in four hole casees, and perpendicular body number of times obviously reduces.In the experimental applications dosage range, this medicine does not have obvious influence to the laboratory animal activity.
Three .GABA receptor blocking agent Flumazenil are to the laboratory observation of " Chinese patent drug " capsule anxiety drug effect function influence
1. make a summary
The purebred mice of ICR is adopted in this experiment, and is male, body weight 16-18g.Being subjected to the reagent thing is Flumazenil and " Chinese patent drug " capsule.Adopt high platform cross platform labyrinth; Four hole casees and activity are measured picture as experimental facilities.Observe; Behavior change behind the oral Flumazenil of record experiment mice and " Chinese patent drug " pharmaceutical capsules.Experiment purpose is observation and understands the influence of GABA receptor blocking agent to the effect of " Chinese patent drug " capsule anxiety drug effect, inquires into " Chinese patent drug " capsule pharmacotoxicological effect mechanism antianxity.
Oral " Chinese patent drug " capsule 31.3mg/kg+Flumazenil 1.25mg/kg group and simple oral " Chinese patent drug " capsule 31.3mg/kg matched group are established in experiment; Establish simultaneously the stable matched group of blank group and positive drug in addition.Every group of 10 test mices.Adopt and irritate the stomach method to " Chinese patent drug " pharmaceutical capsules, intraperitoneal injection is given the Flumazenil medicine.60 minutes beginning test observations after the administration.
Experimental result shows:
GABA receptor blocking agent Flumazenil has the capsular drug action of impedance " Chinese patent drug ".Show as:
1) GABA receptor blocking agent Flumazenil can reduce oral " Chinese patent drug " capsule 31.3mg/kg treated animal and enters high platform cross labyrinth open sides number of times and holdup time, makes it near blank group level.
2) GABA receptor blocking agent Flumazenil can reduce oral " Chinese patent drug " capsule 31.3mg/kg treated animal number of times of popping one's head in four hole casees.
With above-mentioned zoopery result is foundation, infers that the drug action antianxity of " Chinese patent drug " capsule may to act on GABA receptor related with this medicine.
2. experiment purpose:
Observation and understanding GABA receptor blocking agent Flumazenil inquire into the mechanism of " Chinese patent drug " capsule angst resistance effect to the influence of " Chinese patent drug " capsule drug action.
3. materials and methods:
(1) animal: adopt purebred ICR mice; Male; Body weight 15-17g.The secondary Animal House is conventional raises.Animal House temperature: 24 ± 2 ℃; Humidity: 60%; Light application time: 12 hours.
(2) be subjected to the reagent thing:
1) " Chinese patent drug " capsule: brown powder; The active drug composition is that the deduction of 10% acetic acid medium-height grass liquid medicine divides, and this medicine dissolubility in water is good.Preserve under the room temperature lucifuge drying.
2) Flumazenil injection, specification: 0.5mg/5ml, room temperature preservation.Purity＞99%; By Switzerland, F.Hoffmann-La Roche, Ltd, Basel provides, and sees package insert.
(3) test grouping and dosage:
1) simple " Chinese patent drug " capsule 31.3mg/kg group;
2) " Chinese patent drug " capsule 31.3mg/kg+Flumazenil 1.25mg/kg group;
3) blank group;
4) the stable 1mg/kg group of positive drug.Every group of 10 test mices.
" Chinese patent drug " pharmaceutical capsules is pressed per weight dosage and is prepared with the distilled water dissolving, and the administration of stomach method is irritated in employing in 5 minutes behind lumbar injection Flumazenil medicine.Every mouse stomach volume is 0.2ml.In experiment beginning administration in preceding 60 minutes.The blank group is pressed the equal-volume distilled water and is irritated stomach.
4. experimental facilities:
(1) high platform cross platform labyrinth: cross platform labyrinth is the plank self-control of 0.5cm by thickness, and its bottom shape is cruciform shape, is divided into four districts, i.e. two symmetric open zones, and its bottom area is respectively 25 * 5cm; Two symmetric enclosed areas, its bottom area is respectively 25 * 5cm, and the enclosed area 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 and the time of stop.
(2) four hole casees: by thickness is the wood-block self-control of 0.5cm.Its casing specification is 60 * 60 * 30cm.Box bottom has the circular hole of four diameter 4cm apart from four jiaos of 5cm places.During on-test experimental animal is put into case center, four holes, allow experimental animal free movable in casing.Write down probe and the perpendicular body number of times of test mice in four hole casees in 300 seconds simultaneously.
The experimental record method: when the anterior contact of test mice nose circular hole edge, record test mice probe once; When the test mice biped lifts when liftoff, the perpendicular body of record mice once.
(3) the optoelectronic induction activity is measured the case hanger bracket: by four diameter 25cm, the transparent round tank of high 15cm is formed, equal portions are fixed 6 optoelectronic induction probes on the bucket wall, when experiment mice is movable in bucket, optoelectronic induction probe automatically the record mice through the number of times of optoelectronic induction probe, 300 seconds minutes of computer control record and movable number of times.
Above-mentioned experimental facilities is put into fixedly laboratory, makes every effort to quiet after the experiment beginning, avoids noise and other interference factor to influence experimental result as far as possible.
5. observation index:
1) mice enters cross platform labyrinth open sides number of times and percentage rate in 300 seconds.
2) mice enters cross platform labyrinth closed side number of times and percentage rate in 300 seconds.
3) mice enters cross platform labyrinth open sides time and percentage rate in 300 seconds.
4) mice enters cross platform labyrinth closed side time and percentage rate in 300 seconds.
5) the mice number of times of in four hole casees, popping one's head in 300 seconds.
6) mice perpendicular body number of times in four hole casees in 300 seconds.
7) mice activity optoelectronic induction number of times in 300 seconds.
6. statistical analysis:
All experimental data adopts average ± standard deviation (X ± S) expression.Each administration group data and blank group are carried out common-size analysis.The T check is carried out statistics relatively to data between group.
7. experimental result:
Table 4. animal enters high platform cross labyrinth open sides and closed side number of times and percentage comparisons (n=10)
| Group | Open sides | The closed side | ||
| Number of times | ％ | Number of times | ％ | |
| " Chinese patent drug " Capsules group " Chinese patent drug " capsule blocking-up group tranquilizer matched group blank group merely | 10.0±1.41 3.2±1.03 ** 9.6±2.12 4.4±1.43 ** | 44.23±2.87 22.62±6.46 ** 48.06±6.49 22.02±4.65 ** | 12.7±1.57 11.0±2.06 10.1±2.12 15.6±3.92 * | 55.77±2.87 77.38±2.31 ** 51.94±6.49 77.98±4.65 ** |
Statistics compares: compare with simple " Chinese patent drug " Capsules group
*: p＜0.01;
*: p＜0.05
Table 5. animal is open sides and closed side holdup time and percentage comparisons (n=10) in high platform cross labyrinth
| Group | Open sides | The closed side | ||
| Time | ％ | Time | ％ | |
| " Chinese patent drug " Capsules group " Chinese patent drug " capsule blocking-up group tranquilizer matched group blank group merely | 59.5±7.58 26.6±9.12 ** 72.3±12.59 * 31.7±8.00 ** | 20.81±2.55 9.26±3.26 ** 25.04±4.06 11.02±2.68 ** | 226.3±7.12 261.6±12.14 * 215.9±10.63 255.4±7.78 * | 79.19±2.55 90.74±3.26 ** 74.96±4.06 88.98±2.68 * |
Statistics compares: compare with simple " Chinese patent drug " Capsules group
*: p＜0.01;
*: p＜0.05
Each organizes the mice probe of taking medicine table 6., the comparison n=10 that perpendicular body and activity change
| Group | The perpendicular body total degree of probe | The probe number of times | Perpendicular body number of times | Movable number of times |
| " Chinese patent drug " Capsules group " Chinese patent drug " capsule blocking-up group tranquilizer matched group blank group merely | 39.0±3.83 42.1±6.23 43.8±7.35 37.1±4.43 | 20.5±4.33 17.0±3.16 * 23.9±3.99 17.4±2.55 * | 18.5±2.72 25.1±5.15 * 19.9±4.41 29.7±3.40 ** | 307.0±28.76 278.0±23.32 283.5±31.94 298.7±42.90 |
Statistics compares: compare with simple " Chinese patent drug " Capsules group
*: p＜0.05;
*: p＜0.01
The experimental result of table 4-6 shows;
1) compares with simple oral " Chinese patent drug " capsule 31.3mg/kg treated animal, simultaneously oral " Chinese patent drug " capsule 31.3mg/kg and GABA receptor blocking agent Flumazenil1.25mg/kg group laboratory animal enters high platform cross labyrinth open sides number of times and is trapped in the open sides time and obviously reduces P＜0.05-0.01.This group mice enters high platform cross labyrinth open sides number of times and is trapped in the open sides time average and the blank class mean is approaching, P＞0.05.
2) compare with simple " Chinese patent drug " capsule 31.3mg/kg treated animal, simultaneously oral " Chinese patent drug " capsule and the GABA receptor blocking agent Flumazenil group laboratory animal number of times of popping one's head in four hole casees is lower than simple oral " Chinese patent drug " Capsules group, statistics compares, p＜0.05.
3) all animal photoelectricity activities of taking medicine are measured with the blank group and are not more found obviously to reduce.
Conclusion: GABA receptor blocking agent Flumazenil has the drug action antianxity of impedance " Chinese patent drug " capsule.With above-mentioned zoopery result is foundation, can infer that the drug action antianxity of " Chinese patent drug " capsule may be receptor related with GABA.
Sum up:
(1) " Chinese patent drug " capsule 50% stable dosage (IC that suppresses
50): 70.12ng/ml..
(2) Gao Tai labyrinth, four hole casees and photoelectricity active box measurement device experimental result show: oral " Chinese patent drug " capsule can obviously change the behavioral trait of experiment mice on test set, mainly show as and enter high platform cross labyrinth open sides number of times and time and percentage rate and all obviously increase, probe and perpendicular body increased frequency in four hole casees than the blank group.Above line is for a change consistent with the stabile drug action of known antianxiety drugs.This medicine is showing with oral 30mg/kg dosage the most to the dose-effect relationship of experiment mice behavioral implications." Chinese patent drug " capsule does not have obvious influence to the nervous system and the muscular strength of laboratory animal.
(3) GABA receptor blocking agent Flumazenil
1) compares with simple oral " Chinese patent drug " capsule 31.3mg/kg treated animal, simultaneously oral " Chinese patent drug " capsule 31.3mg/kg and GABA receptor blocking agent Flumazenil1.25mg/kg group laboratory animal enters high platform cross labyrinth open sides number of times and is trapped in the open sides time and obviously reduces P＜0.05-0.01.This group mice enters high platform cross labyrinth open sides number of times and is trapped in the open sides time average and the blank class mean is approaching, P＞0.05.
2) compare with simple " Chinese patent drug " capsule 31.3mg/kg treated animal, simultaneously oral " Chinese patent drug " capsule and the GABA receptor blocking agent Flumazenil group laboratory animal number of times of popping one's head in four hole casees is lower than simple oral " Chinese patent drug " Capsules group, statistics compares, p＜0.05.
3) all animal photoelectricity activities of taking medicine are measured with the blank group and are not more found obviously to reduce.
These experimental result explanations: GABA receptor blocking agent Flumazenil has impedance " Chinese patent drug " capsule drug action antianxity.
Comprehensive every test result shows that " Chinese patent drug " capsule has drug action to anxiety.
Claims (5)
1. a new compound Chinese patent medicine " Chinese patent drug " that is used for the treatment of all kinds of anxiety diseases is characterized in that, it is made up and made by Chinese medicine Radix Bupleuri, Rhizoma Corydalis, Flos Albiziae fleece-flower root rattan.
2. compound Chinese patent medicine as claimed in claim 1 " Chinese patent drug " is characterized in that, the various main components in the above-mentioned compound Chinese patent medicine: the weight ratio of the prescription of Radix Bupleuri, Rhizoma Corydalis, Flos Albiziae, Caulis Polygoni Multiflori is in following scope:
Radix Bupleuri 25.80～38.70%; Rhizoma Corydalis 18.00～27.00%; First Ukraine rattan 18.00～27.00%; He Huan spends 18.00～27.00%.
3. compound Chinese patent medicine as claimed in claim 1 or 2 " Chinese patent drug " is characterized in that, the various main components in the above-mentioned compound Chinese patent medicine, and the optimum weight ratio of the prescription of Radix Bupleuri, Rhizoma Corydalis, Flos Albiziae, Caulis Polygoni Multiflori is:
Radix Bupleuri 32.50%; Rhizoma Corydalis 22.50%; First Ukraine rattan 22.50%; He Huan spends 22.50%.
4. the compound Chinese patent medicine described in claim 1 or 2 is characterized in that, this compound Chinese patent medicine is made following various dosage form: tablet; Capsule; Drop pill; Oral liquid and injection.
5. the compound Chinese patent medicine described in claim 3 is characterized in that, this compound Chinese patent medicine is made following various dosage form: tablet; Capsule; Drop pill; Oral liquid and injection.
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| WO2018042384A1 (en) * | 2016-09-02 | 2018-03-08 | Pharmacogenetics Limited | Compositions of medicinal plants for reducing the effects of aging, prevention and treatment of age-related neurodegenerative diseases, and treatment of anxiety and sleep disorders |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2018042384A1 (en) * | 2016-09-02 | 2018-03-08 | Pharmacogenetics Limited | Compositions of medicinal plants for reducing the effects of aging, prevention and treatment of age-related neurodegenerative diseases, and treatment of anxiety and sleep disorders |
| CN109641023A (en) * | 2016-09-02 | 2019-04-16 | 华晶基因技术有限公司 | For delaying senescence, old neurodegenerative disease, and the Chinese herbal medicine efficient combination for the treatment of anxiety and sleep disturbance disease are prevented and treated |
| US10722547B2 (en) | 2016-09-02 | 2020-07-28 | Pharmacogenetics Limited | Compositions of medicinal plants for reducing the effects of aging, prevention and treatment of age-related neurodegenerative diseases, and treatment of anxiety and sleep disorders |
| CN109641023B (en) * | 2016-09-02 | 2021-11-05 | 华晶基因技术有限公司 | Chinese herbal medicine effective combination for delaying senility, preventing and treating senile neurodegenerative diseases, anxiety and sleep disorder |
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