CN101181486B - Depression treating medicine and preparation method thereof - Google Patents
Depression treating medicine and preparation method thereof Download PDFInfo
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- CN101181486B CN101181486B CN200710093095A CN200710093095A CN101181486B CN 101181486 B CN101181486 B CN 101181486B CN 200710093095 A CN200710093095 A CN 200710093095A CN 200710093095 A CN200710093095 A CN 200710093095A CN 101181486 B CN101181486 B CN 101181486B
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Abstract
The invention provides a medicine for curing depression, which is characterized in that the medicine consists of the following raw medical materials with corresponding weight proportions: 625 to 1680 shares of spina date seed, 580 to 1720 shares of foreign ginseng, 385 to 970 shares of rhizoma anemarrhenae, 440 to 1100 shares of root poria, 520 to 1280 shares of radix rehmanniae rehmannia, 470 to 1310 shares of grass-leaved sweetflag, 300 to 900 shares of milkwort and 350 to 1050 shares of patchouli. The invention provides a Chinese patent medicine with small dose, high content of effective component, reliable curative effect for curing depression, less serious side effect and low cost for clinic.
Description
Technical field
The present invention relates to a kind of medicine for the treatment of depression and preparation method thereof, belong to the field of Chinese medicines.
Background technology
Depression be a kind of low with the emotion persistence be the mental disorder of basic feature, often be mixed with bradyphrenia and behavior sluggishness, and various somatization symptom.During paralepsy, it is painful that the patient feels deeply, and be difficult to be understood by the people, more increases its painful degree.Patient's social function is badly damaged, and quality of life obviously descends, even suicide takes place, and the homicide rate of depression is up to 10%～17%.Cause serious consequence for society and family.If existing antidepressant class drug main Western medicine class not only costs an arm and a leg, and bigger toxic and side effects or addiction is arranged.
Summary of the invention
The object of the present invention is to provide the Chinese patent medicine of the treatment depression that a kind of curative effect is reliable, toxic and side effects is little and with low cost.
Another object of the present invention provides the preparation method of this Chinese patent medicine
The object of the present invention is achieved like this: a kind of Chinese patent medicine for the treatment of depression is characterized in that it is to be made by following bulk drugs: 350～1050 parts of 625～1680 parts of Semen Ziziphi Spinosaes, 580～1720 parts of Radix Panacis Quinquefoliis, 385～970 parts of the Rhizoma Anemarrhenaes, 440～1100 parts of Poria cum Radix Pinis, 520～1280 parts of Radix Rehmanniae, 470～1310 parts of Rhizoma Acori Graminei, 300～900 parts of Radix Polygalaes and Herba Pogostemonis.
The preferable amount of above-mentioned each crude drug is:: 350 parts of 625 parts of Semen Ziziphi Spinosaes, 580 parts of Radix Panacis Quinquefoliis, 385 parts of the Rhizoma Anemarrhenaes, 440 parts of Poria cum Radix Pinis, 520 parts of Radix Rehmanniae, 470 parts of Rhizoma Acori Graminei, 300 parts of Radix Polygalaes and Herba Pogostemonis.
Another object of the present invention, promptly the preparation method of above-mentioned Chinese patent medicine can adopt the conventional method of Chinese medicine preparation to be prepared into any conventional oral preparations.
Preferably, the preparation method of above-mentioned Chinese patent medicine comprises the steps:
(1) at first Rhizoma Acori Graminei in the described weight portion proportioning and Herba Pogostemonis are mixed, decoct with water, it is standby to collect volatile oil with the steam distillation extracting method, and it is standby to get filtrate A after water decoction filters;
(2) medicinal residues that obtain after described water decoction is filtered mix with surplus stock medicine in the described weight portion proportioning, decoct with water extraction more than 1 time, the merging decoction liquor, and B filters to get filtrate;
(3) merging filtrate A and liquor B and by macroporous resin, the reuse ethanol elution, collect that ethanol elution concentrates, after the drying dry extract;
(4) dry extract is pulverized the back and add the active component that described volatile oil just has been prepared into medicine of the present invention;
(5) acceptable auxiliary on the active component adding pharmaceutics of described medicine of the present invention is made dosage form pharmaceutically commonly used.
Bring into play drug effect better for each raw material that makes medicine of the present invention, the above-mentioned water vapour distillation time is 2～6 hours, preferred 5 hours; Above-mentioned decocting with water when extracting 4 times, the 1st, 2 time decocts amount of water is 12 times of amounts of raw medicinal herbs, the 3rd, 4 time decocts amount of water is 8 times of amounts of raw medicinal herbs, decocts at every turn and is advisable in 40 minutes; Above-mentioned macroporous resin preferably uses D
101The type macroporous resin; Above-mentioned is 65～85% with the concentration of alcohol in the ethanol elution macroporous resin; Above-mentioned ethanol elution simmer down to is behind 1.0～2.20 the extractum T=60 ℃ relative density, preferably adds an amount of silicon dioxide again and mixes and pulverize, and sieves and dry back adds the active component of above-mentioned volatile oil preparation cost invention medicine.
Above-mentioned adding silicon dioxide mixes the pulverizing back and crosses 60 mesh sieves, and dry under 65～70 ℃ of temperature, makes its dried moisture in 10%.
For its medicine of the present invention is discharged slowly in vivo, prolong medicine of the present invention release time in vivo, curative effect with effective raising medicine activity component of the present invention, above-mentioned volatile oil is before the active component of preparation cost invention medicine, by volatile oil: betacyclodextrin: water=mixed of 1: 5: 50 is rolled into the betacyclodextrin clathrate of volatile oil.
The step that above-mentioned volatile oil mixes parcel is: at first the volatile oil in the said ratio is added an amount of dehydrated alcohol mixing; To be cooled to 75～55 ℃ again after betacyclodextrin in the said ratio and the dissolving of water Hybrid Heating then, and place on the constant temperature blender with magnetic force, splash into the alcoholic solution of above-mentioned volatile oil gradually, stirred 1 hour, be cooled to room temperature in 75～55 ℃ of constant temperature; Hid 24 hours in 4～5 ℃ refrigerator and cooled at last, filter, after 50 ℃ of dryings and pulverizing, obtain the betacyclodextrin clathrate of volatile oil.
The active component of medicine of the present invention can add acceptable auxiliary on the pharmaceutics and make dosage form pharmaceutically commonly used.For example add disintegrating agent, lubricant, binding agent etc. and be prepared into any peroral dosage form commonly used, as capsule, tablet, granule, pill, oral liquid, powder, sublimed preparation, unguentum etc. with the method for Chinese medicinal of routine.
The inventor sees diseases such as restlessness of asrhenia type and insomnia, cardiopalmus susceptible to get angry more at depression, pathogenesis be disturb on deficiency of liver-blood, blood failing to tonify the heart and blood-deficiency leading to hyperactivity of the liver, the empty sun due to, with the method for nourishing the liver blood, heart-spleen boosting, clearind deficient heat, the relieving restlessness of calming the nerves, selected medical material, form basis side's treatment depression of goods of the present invention.Reuse in the side that Semen Ziziphi Spinosae nourishing the liver blood, mind calming are refreshing to be monarch drug, assistant is with Radix Panacis Quinquefolii, Poria cum Radix Pini, Radix Polygalae invigorating the heart and spleen, mind tranquilizing and the heart calming; Radix Rehmanniae, Rhizoma Anemarrhenae clearind deficient heat is removed fidgets due to deficiency; Rhizoma Acori Graminei, Herba Pogostemonis Fructus Alpiniae Oxyphyllae inducing resuscitation; All medicine compatibilities are income gas nourishing blood to tranquillize the mind altogether, and the effect of clearing heat and relieving fidgetness makes the blood nourishing of motive foot, conscience active, and then cloudy yang invigorating is dived.Deficiency-heat is moved back and fidgets due to deficiency is removed, then dysphoria and insomnia, uneasy sleeping at night, depressed all disease spontaneous recoverys such as cardiopalmus susceptible to get angry.
The inventor is according in for many years clinical accumulation aspect the traditional medicine, the goods of the present invention that adopt modern technology to make, and it is little to have a dose, the active constituent content height, treatment depression curative effect is reliable, the advantage that side effect is little and with low cost.
Below further set forth the beneficial effect of medicine of the present invention by testing example.These test examples have comprised the pharmacodynamics test and the toxic and side effects test of medicine of the present invention.
The medicine that makes in [test example 1] embodiment of the invention 4 is to the influence of mice forced swimming experiment
Test method:
Choosing body weight is 60 of 18～22g male mice in kunming, conform and raised 1 day, be divided into five groups (every group is 12) at random: ((high dose group that promptly gives goods 10g crude drug of the present invention/kg), medicine of the present invention (promptly gives goods 20g crude drug of the present invention/kg), positive drug group (promptly giving amitriptyline hydrochloride 20mg/kg) and matched group (promptly giving distilled water) to the low dose group of medicine of the present invention promptly to give the middle dosage group of goods 5g crude drug of the present invention/kg), medicine of the present invention; Administration every day 1 time, administration volume are 0.2ml/10g body weight (matched group gives with the volume distilled water), continuous 7 days.
Behind the last administration 45min, with mice by only putting into internal diameter 10cm, in the glass circle cylinder of high 20cm, depth of water 10cm in the cylinder, 25 ± 1 ℃ of water temperatures, 1 in every cylinder, the accumulative total dead time that begins to observe and write down mice in the 4min behind the swimming 2min (stops to struggle or being floating state, the persistent period of tiny limb motion to keep head to keep afloat only arranged), the time is to remember second.Adopt mice forced swimming experiment accumulative total dead time and LVFS to calculate to the mouse swimming test result, administration group and matched group are compared, the result tests with the t method of inspection.
LVFS: (C-T)/C * 100% (remarks: the LVFS of matched group is 0.0%)
Wherein: the accumulative total dead time of C one control group mice, the accumulative total dead time of T one administration group mice.
Result of the test sees Table 1.
Table 1 medicine of the present invention is to influence (x ± SD, n=12) (perusal) of mice forced swimming test
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Dead time (S) | LVFS (%) |
| The low dose group of medicine of the present invention | 5 | 12 | 87.9±31.2 | 9.2 |
| The middle dosage group of medicine of the present invention | 10 | 12 | 70.2±25.9 * | 27.5 |
| The high dose group of medicine of the present invention | 20 | 12 | 50.6±19.0 ** | 47.7 |
| Positive drug group (amitriptyline hydrochloride) | 20mg | 12 | 49.4±17.8 ** | 49.0 |
| Matched group | / | 12 | 96.8±31.8 | 0.0 |
Compare with matched group:
*P＜0.05,
*P＜0.01
By table 1 as seen: compare with matched group, medicine high dose of the present invention and middle dosage can make the accumulative total dead time significance of the desperate model mice of swimming shorten, and LVFS is respectively 47.8% and 27.5%; Medicine low dosage of the present invention has the trend that makes its shortening, and LVFS only is 9.2%.Amitriptyline hydrochloride also can significance shortens the accumulative total dead time (P＜0.01) of depression mice (the desperate model of swimming), and LVFS is 49.0%.This results suggest medicine height of the present invention, middle dosage can obviously shorten the dead time of the desperate model mice of swimming.
The medicine that makes in [test example 2] embodiment of the invention 1 is to the influence of rat forced swimming test
Test method:
Choose 50 of body weight 160～180g male SD rats, be divided into 5 groups (10 every group) at random: ((high dose group that promptly gives goods 7g crude drug of the present invention/kg), medicine of the present invention (promptly gives goods 14g crude drug of the present invention/kg), positive drug group (promptly giving amitriptyline hydrochloride 15mg/kg), matched group (promptly giving distilled water) to the low dose group of medicine of the present invention promptly to give the middle dosage group of goods 3.5g crude drug of the present invention/kg), medicine of the present invention; Administration every day 1 time (the administration volume is the 1.0ml/100g body weight), continuous 7 days.Behind the medicine 45min with rat put into one by one the lucite cylinder (internal diameter 20cm, high 40cm, depth of water 15cm, 25 ± 1 ℃ of water temperatures, 1 in every cylinder) forced swimming 15min, take out subsequently to dry and put into cage.Test behind the 24h, rat is put into glass cylinder again one by one, observe 5min continuously, the accumulative total rat is the dead time (stop to struggle, be floating erectility, the persistent period of tiny limb motion to keep head to keep afloat arranged once in a while) in water.Before test, given before the 45min by the reagent thing.The result tests with the t method of inspection.
Result of the test sees Table 2.
Table 2 medicine of the present invention is to influence (x ± SD, n=10) (perusal) of the mandatory non-swimming time of rat
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Dead time (S) | LVFS (%) |
| The low dose group of medicine of the present invention | 3.5 | 10 | 91.7±29.5 * | 26.0 |
| The middle dosage group of medicine of the present invention | 7 | 10 | 78.6±20.5 ** | 36.6 |
| The high dose group of medicine of the present invention | 14 | 10 | 75.3±24.5 ** | 39.2 |
| Positive drug group (amitriptyline hydrochloride) | 15mg | 10 | 65.0±26.2 ** | 47.2 |
| Matched group | / | 10 | 123.7±34.2 | 0.0 |
Compare with matched group:
*P＜0.05,
*P＜0.01
When rat was put into water in test the previous day, at the bottom of beginning to swim desperately and attempting to climb up barrel or slip into tin, animal activity weakened behind 2～3min, arranged between the activity the motionless intermittence of long period, and the intermittent time is more and more longer.The time of motionless state accounts for 80% of total time behind 5～6min.Behind the 24h rat is reentered in the cylinder, the floating behavior in 5min of rat does not on the same group have repeatability preferably.By table 2 as seen: compare with matched group, each dosage of medicine of the present invention obviously shortens the accumulative total dead time of rat forced swimming, and LVFS is respectively 26.0%, 36.6% and 39.2%.This results suggest medicine of the present invention has the depression effect of the anti-forced swimming rat of significance.
The medicine that makes in [test example 3] embodiment of the invention 4 is to the influence of mouse tail suspension experiment
Test method:
Choose body weight 20 ± 2g male mice in kunming, 45min behind the last medicine is fixed on mice tail end 2cm place on the outstanding tail support, makes animal be the reversal of the natural order of things state, and head destage face 5cm isolates the animal sight line with plate all around.Dead time in the observed and recorded mice 6min; All the other are with test example 1.
Result of the test sees Table 3.
Table 3 medicine of the present invention is to influence (x ± SD, n=12) (perusal) of mouse tail suspension dead time
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Dead time (S) | LVFS (%) |
| The low dose group of medicine of the present invention | 5 | 12 | 121.0±47.2 * | 28.0 |
| The middle dosage group of medicine of the present invention | 10 | 12 | 128.6±31.8 * | 23.4 |
| The high dose group of medicine of the present invention | 20 | 12 | 98.7±29.7 ** | 41.2 |
| Positive drug group (amitriptyline hydrochloride) | 20mg | 12 | 56.2±25.0 ** | 66.5 |
| Matched group | / | 12 | 168.0±42.6 | 0.0 |
Compare with matched group:
*P＜0.05,
*P＜0.01
By table 3 as seen: after administration group and control group mice were inverted and are hung, it was movable fierce all to show as mice, and outstanding excellent amplitude of fluctuation is big, wipes panel height up and down to sop up liquid.Different is: administration group mice is after the excited and exciting general time, is in despair (head sticks up, body and extremity motionless) state, be actually at movable tired back timeout, and be again fierce activity subsequently.And short the control group mice excitation activity time, also can recover after stopping a moment temporarily, but outstanding rod swing weakens, amplitude reduces, and the persistent period shortens, even motionless (being in desperate state).This results suggest gives the basic, normal, high dosage of medicine of the present invention all can obviously shorten the dead time of mice under outstanding shape of tail attitude, and LVFS is respectively 28.0%, 23.4% and 41.2%.
The medicine that makes in [test example 4] embodiment of the invention 2 causes the mice blepharoptosis, the inductor relaxing the bowels with purgatives of warm nature falls and causes the movable influence that reduces of mice reserpine
Test method:
Choose body weight 20 ± 2g male mice in kunming, after conforming 1 day, be divided into six groups at random, every group 14: normal control group (distilled water), model control group (distilled water), positive drug group (amitriptyline hydrochloride 20mg/kg), the basic, normal, high dosage group of medicine of the present invention (be respectively 5,10,20g crude drug/kg), administration every day 1 time (the administration volume is the 0.2ml/10g body weight), continuous 7 days.
Use temperature instrumentation anus temperature 2 times before last 1 administration, its mean is as basal body temperature; Every group at interval 6min be subjected to reagent, except that the normal control group behind all the other animals administers immediately iv give reserpine 1mg/kg.Observe respectively behind the iv reserpine 1h:
(1) respectively organize mice blepharoptosis degree and antagonism percentage rate %, and add up in the mode of score, standards of grading are: widening the view fully is that to close one's eyes in 0 minute, 1/4 be to close one's eyes in 1 minute, 1/2 to be that to close one's eyes in 2 minutes, 3/4 be 3 minutes, to close one's eyes fully being 4 minutes.
Antagonism percentage rate %:(C-T)/C * 100% (remarks: the antagonism percentage rate of model control group is 0.0%);
The scoring of C one model group rat blepharoptosis;
The scoring of T one administration group rat blepharoptosis.
(2) anus temperature: thermometer is inserted mice anal 1.5～2cm place measure the anus temperature, compare the difference that administration group and matched group anus temperature change, and measure the difference of different time points (every interval 1h observes 6h continuously) administration group and the variation of matched group anus temperature behind the iv reserpine.
(3) activity: mice is placed in the circle of diameter 7.5cm, observes the animal activity situation, all the person is effective for improving activeness from circle (be lower than 5s, answer repeated measures to determine) for extremity in 15s, otherwise it is invalid to be defined as.
(1), (2) index are carried out statistical analysis with t check analysis method; Index (3) is used X
2The check analysis method is carried out statistical analysis.
Result of the test sees Table 4, table 5, table 6
The influence of table 4 medicine antagonism of the present invention iv reserpine induced mice blepharoptosis (x ± SD)
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Blepharoptosis score value (branch) | Antagonism percentage rate (%) |
| The normal control group | / | 14 | / | / |
| Model control group | / | 14 | 3.00±0.34 | / |
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Blepharoptosis score value (branch) | Antagonism percentage rate (%) |
| The low dose group of medicine of the present invention | 5 | 14 | 2.64±0.46 * | 12.0 * |
| The middle dosage group of medicine of the present invention | 10 | 14 | 2.11±0.84 * | 29.7 * |
| The high dose group of medicine of the present invention | 20 | 14 | 2.00±0.62 * | 33.3 * |
| Positive drug group (amitriptyline hydrochloride) | 20mg | 14 | 1.25±0.98 ** | 58.3 * |
Compare with model control group:
*P＜0.05,
*P＜0.01.
By table 4 as seen: the mice blepharoptosis that the equal energy of each dosage group of medicine of the present invention antagonism reserpine causes, the high, medium and low dosage effect of medicine of the present invention is remarkable, and the antagonism percentage rate is respectively 33.3%, 29.7% and 12.0%.
The influence that table 5 medicine antagonism of the present invention reserpine induction mouse temperature descends (x ± SD)
Compare with model control group:
*P＜0.05,
*P＜0.01.
By table 5 as seen, significantly inducing mouse body temperature decline behind the iv reserpine, along with the time lengthening mouse temperature descends many more, medicine height of the present invention, middle dosage significance antagonism iv reserpine induction body temperature descend, action time, medicine had certain effect after surpassing 4h, but acts on not obvious from 1h～3h, along with the prolongation of time, antagonism iv reserpine induction mouse temperature decline effect is weak (the results are shown in Table 5) more and more.
The influence that the activity of table 6 medicine antagonism of the present invention reserpine induced mice reduces (x ± SD)
By table 6 as seen: medicine of the present invention has certain antagonism to movable minimizing of mice that reserpine causes.
The result of comprehensive above [test example 4] as can be known, after blepharoptosis appearred in mice behind the iv reserpine, body temperature descends and activity weakens, each dosage group of medicine of the present invention can be resisted above-mentioned reserpinization effect.
The medicine that makes in [test example 5] embodiment of the invention 4 causes the influence of rat blepharoptosis to reserpine
Test method is with [test example 4].
Result of the test sees Table 7.
Table 7 medicine of the present invention is to the effect of rat blepharoptosis due to the reserpine (x ± SD)
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Blepharoptosis scoring (branch) | Antagonism percentage rate (%) |
| The normal control group | / | 12 | 0.0±0.0 | / |
| Model control group | / | 12 | 3.6±0.7 | 0.0 |
| The low dose group of medicine of the present invention | 3.5 | 12 | 2.6±1.2 | 27.7 |
| The middle dosage group of medicine of the present invention | 7.0 | 12 | 2.5±1.1 * | 29.0 |
| The high dose group of medicine of the present invention | 14.0 | 12 | 2.2±0.8 * | 38.9 |
| Positive drug group (amitriptyline hydrochloride) | 15mg | 12 | 2.0±1.3 * | 44.4 |
Compare with matched group:
*P＜0.05,
*P＜0.05
By table 7 as seen: compare with matched group, medicine height of the present invention, middle dosage can obviously resist the rat blepharoptosis that reserpine causes, the antagonism percentage rate is respectively 38.9% and 29.0%.
The medicine that makes in [test example 6] embodiment of the invention 1 is to the influence of levodopa behavior effect
Test method:
Choose body weight 20 ± 2g male mice in kunming, after conforming 1 day, be divided into six groups (12 every group) at random: normal control group (distilled water), model control group (distilled water), positive drug group (amitriptyline hydrochloride 20mg/kg), the basic, normal, high dosage group of medicine of the present invention (be respectively 5,10,20g crude drug/kg), administration every day 1 time (the administration volume is the 0.2ml/10g body weight), continuous 7 days.
45min behind the last medicine, all the other animals ip levodopa 150mg/kg respectively except that the normal group mice are placed in the cage mice is single subsequently, and are movable frequent in the observed and recorded 30min, do not stop the number of animals of walking about back and forth.To result of the test X
2Statistical analysis is carried out in the check of method of inspection analytic process.
Result of the test sees Table 8.
Table 8 medicine of the present invention is to the influence of levodopa behavior effect
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Unmovable Mus number (only) | Movable Mus number (only) | Positive rate (%) |
| The normal control group | / | 12 | 12 | 0 | / |
| Model control group | / | 12 | 12 | 0 | 0.0 |
| The low dose group of medicine of the present invention | 5 | 12 | 10 | 2 | 16.7 |
| The middle dosage group of medicine of the present invention | 10 | 12 | 6 | 6 * | 50.0 |
| The high dose group of medicine of the present invention | 20 | 12 | 9 | 3 | 25.0 |
| Positive drug group (amitriptyline hydrochloride) | 20mg | 12 | 8 | 4 | 33.3 |
Compare with matched group:
*P＜0.05
By table 8 as seen, only give mice goods of the present invention or levodopa, all no abnormal change of animal behavior, and give to give levodopa again behind the mice medicine of the present invention, then there is the part animal not stop back and forth to walk about along cage.Compare with model control group, the number of animals that the dosage group is walked up and down in the medicine of the present invention has significance to increase, and the number of animals that occurs walking up and down is 6, has reached 50%; All the other administration treated animals also have and increase, but do not have statistical significance.Point out medicine of the present invention that the behavior effect of strengthening levodopa is had certain promotion.
The influence that the medicine that makes in [test example 7] embodiment of the invention 3 trembles to 5-hydroxy tryptamine acid induced mice
Test method:
Choose body weight 20 ± 2g male mice in kunming, after conforming 1 day, be divided into six groups (12 every group) at random: matched group (distilled water), model control group (distilled water), positive drug group (amitriptyline hydrochloride 20mg/kg), the basic, normal, high dosage group of medicine of the present invention (be respectively 5,10,20g crude drug/kg), administration every day 1 time (the administration volume is the 0.2ml/10g body weight), continuous 7 days.
45min behind the last medicine, all the other mices ip5-hyroxytrypophan 200mg/kg respectively except that normal group are placed in the cage mice is single subsequently, observe the number of animals that occurs trembling in the 20min.Result of the test X
2Statistical analysis is carried out in the check of method of inspection analytic process.
Result of the test sees Table 9.
The influence that table 9 medicine of the present invention trembles to 5-hydroxy tryptamine acid induced mice
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Mus number (only) does not occur trembling | Mus number (only) trembles | Rate (%) appears trembling |
| The normal control group | / | 12 | 12 | 0 | / |
| Model control group | / | 12 | 12 | 0 | 0 |
| The low dose group of medicine of the present invention | 5 | 12 | 9 | 3 | 25.0 |
| The middle dosage group of medicine of the present invention | 10 | 12 | 7 | 5 | 41.7 |
| The high dose group of medicine of the present invention | 20 | 12 | 8 | 4 | 33.3 |
| Positive drug group (amitriptyline hydrochloride) | 20mg | 12 | 7 | 5 | 41.7 |
Compare with matched group:
*P＜0.05
Only give mice goods of the present invention or 5-hydroxy tryptamine acid, the all no abnormal change of animal behavior, and give to give 5-hydroxy tryptamine acid again behind the mice medicine of the present invention, then there is the part animal to occur trembling, with matched group relatively: number of animals to occur be 5 for dosage group and positive drug group in the medicine of the present invention, the probability that occurs has reached 41.7%, has certain influence; All the other medicine treated animals also have and tremble, but a little less than the effect slightly.This really points out medicine of the present invention that the 5-hydroxy tryptamine system is had certain effect, impels 5-hydroxy tryptamine acid inducing mouse to tremble and gets rid of first-class symptom.
The medicine that makes in [test example 8] embodiment of the invention 5 is to the influence of pentobarbital sodium sub-threshold dose mouse sleep time
Test method:
Choose 50 of body weight 20 ± 2g male mice in kunming, after conforming 1 day, be divided into five groups (n=10) at random: matched group (distilled water), positive drug group (stable 10mg/kg), the basic, normal, high dosage group of medicine of the present invention (be respectively 5,10,20g crude drug/kg), administration every day 1 time (the administration volume is the 0.2ml/10g body weight), continuous 7 days.
45min behind the last medicine (stable 30min), ip pentobarbital sodium 30mg/kg, with right reverse disappearance more than 1 minute the person be designated as and sleep, observe the length of one's sleep of sleeping animal, the result checks with t method of inspection analytic process and carries out statistical analysis.
Result of the test sees Table 10.
Table 10 medicine of the present invention is to the influence of the mouse sleep time of subliminal hypnosis dosage pentobarbital sodium (x ± SD)
| Group | Dosage (g/kg) | Number of animals (only) | The length of one's sleep (branch) |
| The blank group | / | 10 | 38.7±15.1 |
| Group | Dosage (g/kg) | Number of animals (only) | The length of one's sleep (branch) |
| The low dose group of medicine of the present invention | 5 | 10 | 30.6±11.4 |
| The middle dosage group of medicine of the present invention | 10 | 10 | 32.3±17.1 |
| The high dose group of medicine of the present invention | 20 | 10 | 42.6±11.9 |
| Positive drug group (amitriptyline hydrochloride) | 10mg | 10 | 93.2±22.2 ** |
Compare with matched group:
*P＜0.05
As shown in table 10, the medicine of the present invention of various dose and animals of control group do not have the difference on the statistics length of one's sleep.
The medicine that makes in [test example 9] embodiment of the invention 6 is to the influence of mice autonomic activities
Test method:
Choose 60 of body weight 20 ± 2g male mice in kunming, after conforming 1 day, be divided into five groups at random: blank group (distilled water), positive drug group (stable 10mg/kg), the basic, normal, high dosage group of medicine of the present invention (be respectively 5,10,20g crude drug/kg), administration every day 1 time (the administration volume is the 0.2ml/10g body weight), continuous 7 days.
45min behind the last medicine (stable 30min), mice is put into the cell of autonomous analyzer, 1 in every case, during mensuration, different little casees is put in every treated animal conversion, adapt to after 5 minutes, write down mice autonomic activities number of times in 10 minutes, result of the test is carried out statistical analysis with the check of t method of inspection analytic process.
Result of the test sees Table 11.
Table 11 medicine of the present invention is to the influence of mice autonomic activities (x ± SD)
| Group | Dosage (the g crude drug/kg) | Number of animals (only) | Movable number of times (inferior/10 minute) |
| The blank group | / | 12 | 188.2±47.2 |
| The low dose group of medicine of the present invention | 5 | 12 | 165.8±42.1 |
| The middle dosage group of medicine of the present invention | 10 | 12 | 179.6±60.2 |
| The high dose group of medicine of the present invention | 20 | 12 | 156.0±56.0 |
| Positive drug group (estazolam) | 10mg | 12 | 95.1±60.6 ** |
Compare with matched group:
*P＜0.05
By table 11 as seen, give the medicine of the present invention of various dose after, outward appearance and the behavior of mice do not have obvious variation, activity freely, movable number of times is similar to matched group, the statistical disposition no significant difference.Showing that medicine of the present invention has antidepressant effect, is not because can strengthen animal activity.
The results of pharmacodynamic test of comprehensive above [test example 1]～[test example 9], medicine of the present invention can obviously shorten animal at " behavior despair " model---the accumulative total " dead time " in forced swimming and the outstanding tail experiment; Big or small rathole blepharoptosis, the inductor relaxing the bowels with purgatives of warm nature that reserpine is caused falls to weaken with autonomic activities all antagonism; Can also the inducing mouse levodopa and 5-hydroxy tryptamine acid behavioristics effect; But to there is no length of one's sleep of the spontaneous activity of normal mouse and pentobarbital sodium sub-threshold dose obvious influence.The above results shows: medicine of the present invention has tangible antidepressant effect to animal, and also hence one can see that, and medicine of the present invention has definite curative effect to the treatment depression.
The acute toxicity test of the medicine that makes in [test example 10] embodiment of the invention 4
Disposable filling medicine of the present invention was observed 14 days, recorded LD
50Be 108.88g/kg, to 24 hours, the mice autonomic activities weakened after the administration, alarmmed hair, appetite decline; The death of mice occurs in after the administration 2 hours and the 2nd, 3 day, and the dead animal when dissected is found flatulence, hyperemia, all the other internal organs no abnormality seens.Dead animal was not observed 14 days, weighed in per 7 days, and each is organized average weight and increases no significant difference, puts to death animal, dissects perusal main organs no abnormality seen.LD
50Be equivalent to 130 times of 60kg body weight adult clinical oral administration day dosages.
The long term toxicity test of the medicine that makes in [test example 11] embodiment of the invention 1
This experimental study irritated the toxic action that the medicine of the present invention of stomach various dose produces rat in continuous 180 days.Test is divided into three dosage groups of matched group and medicine of the present invention, i.e. low dose group (20.0g crude drug/kg), middle dosage group (40.0g crude drug/kg) and high dose group (80.0g crude drug/kg).
Result of the test shows: rat continuous irrigation stomach medicine of the present invention 90 days, 180 days and drug withdrawal 30 days, to compare with the normal control group, and 5～20 minutes independent activity of animals weaken to some extent after the administration of medicine group, and autonomic activities recovers normal gradually after 30 minutes.Each dosage group defecation color is dark partially, and high dose is apparent in view, stop administration after, it is normal that above-mentioned symptom all recovers.Rat diet is not seen obvious influence.Each treated animal is not seen death during the whole test.From 90 days～180 days, medicine high dose of the present invention (the 80.0g crude drug/kg) body weight to male rat has certain reduction, but there was no significant difference.There are indivedual indexs significant difference to occur in animal blood cytology, the biochemical indexes, continue to be administered to 180 days, show no obvious abnormalities, stop to recover normal after the administration at the administration initial stage (promptly 90 days).(80.0g crude drug/kg) indivedual organ weights of group and index increase, drug withdrawal all can recover normal after 30 days to medicine high dose of the present invention.The binding of pathological check result: main organs is not seen the drug-induced pathological change by the present invention.The safe dose that result of the test prompting rat gives medicine of the present invention for a long time is lower to the toxicity of animal when being 40.0g crude drug/kg, thereby provides reference frame for its data for clinical drug use.
The specific embodiment
Further set forth the preparation method of medicine of the present invention below by embodiment.But the present invention not only is confined to these embodiment.
The capsule preparation of [embodiment 1] medicine of the present invention
A kind of capsule for the treatment of depression, its preparation method is as follows:
(1) press the weight portion proportioning of each crude drug in the table 12: at first wherein Rhizoma Acori Graminei and Herba Pogostemonis are mixed, adopt the steam distillation method to extract volatile oil 5 hours, collect volatile oil standby after, it is standby that remaining decocting medical filtration gets filtrate A;
(2) medicinal residues that obtain behind the above-mentioned decocting medical filtration are mixed with all the other crude drug in the above-mentioned weight portion proportioning, decoct with water and extract 4 times, wherein decoct the 12 times of amounts of water that add the 1st, 2 time, 3rd, decoct the 8 times of amounts of water that add 4 times, the each decoction 40 minutes merges 4 times decoction liquor, and B filters to get filtrate;
(3) merge above-mentioned filtrate A and liquor B, and make it pass through D
101After the type macroporous resin adsorption, be 65% ethanol elution with concentration, collect that ethanol elution concentrates, after the drying dry extract, dry extract is 1.0～2.20 T=60 ℃ relative density;
(4) dry extract is pulverized the back and added above-mentioned volatile oil mixing, reinstall the capsule that capsule is just made medicine of the present invention.
The capsule preparation of [embodiment 2] medicine of the present invention
Differently with [embodiment 1] in its preparation process be: the weight portion proportioning of each crude drug is pressed table 12; Decoct with water and the distillating extracting oil time be 4 hours; Pass through D
101After the type macroporous resin adsorption, with concentration 85% ethanol elution; After collecting volatile oil, volatile oil is rolled into reinstalls capsule behind the Benexate Hydrochloride of volatile oil and make capsule.
Wherein the parcel step of volatile oil is: it is an amount of at first volatile oil to be added dehydrated alcohol, mixing is made the alcoholic solution of 50% volatile oil, press volatile oil then: beta-schardinger dextrin-: the proportioning of water=1: 5: 50, with wherein beta-schardinger dextrin-and water Hybrid Heating dissolving postcooling to 75～55 ℃, and place on the constant temperature blender with magnetic force, splash into the alcoholic solution of above-mentioned volatile oil gradually, stirred 1 hour in 75～55 ℃ of constant temperature, mixing speed is 600 rev/mins, is cooled to room temperature again; Hid 24 hours in 4～5 ℃ refrigerator and cooled at last, filter, after 50 ℃ of dryings and pulverizing, just obtain the Benexate Hydrochloride of volatile oil.
All the other steps are with [embodiment 1].
The capsule preparation of [embodiment 3] medicine of the present invention
Differently with [embodiment 1] in its preparation process be: the weight portion proportioning of each crude drug is pressed table 12; Decoct with water and the distillating extracting oil time be 6 hours; Pass through D
101After the type macroporous resin adsorption, with concentration 75% ethanol elution; Be behind 1.0～2.20 the extractum with the ethanol elution simmer down to T=60 ℃ relative density, it is an amount of to add silicon dioxide, mix and pulverize, cross 60 mesh sieves, and it is dry under 65～70 ℃ of temperature, make its dried moisture in 10%, and then add the Benexate Hydrochloride mixing of volatile oil, incapsulate the capsule of just making medicine of the present invention.
All the other steps are with [embodiment 1].
The capsule preparation of [embodiment 4] medicine of the present invention
Differently with [embodiment 1] in its preparation process be: the weight portion proportioning of each crude drug is pressed table 12; Decoct with water and the distillating extracting oil time be 3 hours; All the other steps are with [embodiment 1].
The granule preparation of [embodiment 5] medicine of the present invention
Differently with [embodiment 1] in its preparation process be: the weight portion proportioning of each crude drug is pressed table 12; Decoct with water and the distillating extracting oil time be 2 hours; Concentrated solution by the macroporous resin ethanol elution, reclaim the extractum (T=60 ℃ relative density is 1.0～2.20) that obtains behind the ethanol, the Benexate Hydrochloride that adds volatile oil, and acceptable auxiliary on the pharmaceutics such as lactose, dextrin, starch, Icing Sugar, microcrystalline Cellulose, carboxymethyl starch, mixing, granulate, drying obtains granule.All the other steps are with [embodiment 1].
The preparation tablets of [embodiment 6] medicine of the present invention
The weight portion proportioning of each crude drug is pressed table 12; Concentrated solution by the macroporous resin ethanol elution, reclaim the extractum (T=60 ℃ relative density is 1.0～2.20) that obtains behind the ethanol, the Benexate Hydrochloride that adds volatile oil, and acceptable auxiliary on the pharmaceutics such as lactose, dextrin, starch, Icing Sugar, microcrystalline Cellulose, carboxymethyl starch, mixing is granulated drying, tabletting obtains tablet.All the other steps are with [embodiment 1].
The pill preparation of [embodiment 7] medicine of the present invention
The weight portion proportioning of each crude drug is pressed table 12; Concentrated solution by the macroporous resin ethanol elution, reclaim the extractum (T=60 ℃ relative density is 1.0～2.20) that obtains behind the ethanol, the Benexate Hydrochloride that adds volatile oil, and acceptable auxiliary on the pharmaceutics such as lactose, dextrin, starch, Icing Sugar, microcrystalline Cellulose, carboxymethyl starch, mixing, system soft material, pill, drying obtains pill.All the other steps are with [embodiment 1].
The weight portion proportioning of each crude drug among the embodiment 1～embodiment 7 of table 12 medicine of the present invention
| Component | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Embodiment 7 |
| Semen Ziziphi Spinosae | 675 | 820 | 1580 | 625 | 1680 | 1100 | 750 |
| Radix Panacis Quinquefolii | 590 | 690 | 1680 | 580 | 1720 | 1250 | 650 |
| The Rhizoma Anemarrhenae | 405 | 475 | 860 | 385 | 970 | 900 | 420 |
| Poria cum Radix Pini | 460 | 525 | 1010 | 440 | 1100 | 950 | 490 |
| Radix Rehmanniae | 550 | 615 | 1180 | 520 | 1280 | 1100 | 580 |
| Rhizoma Acori Graminei | 495 | 600 | 1240 | 470 | 1310 | 1150 | 550 |
| Radix Polygalae | 325 | 390 | 830 | 300 | 900 | 850 | 360 |
| Herba Pogostemonis | 370 | 460 | 900 | 350 | 1050 | 950 | 410 |
Claims (8)
1. medicine for the treatment of depression is characterized in that it being to be made by following bulk drugs: 350～1050 parts of 625～1680 parts of Semen Ziziphi Spinosaes, 580～1720 parts of Radix Panacis Quinquefoliis, 385～970 parts of the Rhizoma Anemarrhenaes, 440～1100 parts of Poria cum Radix Pinis, 520～1280 parts of Radix Rehmanniae, 470～1310 parts of Rhizoma Acori Graminei, 300～900 parts of Radix Polygalaes and Herba Pogostemonis.
2. medicine according to claim 1, wherein the consumption of each crude drug is: 350 parts of 625 parts of Semen Ziziphi Spinosaes, 580 parts of Radix Panacis Quinquefoliis, 385 parts of the Rhizoma Anemarrhenaes, 440 parts of Poria cum Radix Pinis, 520 parts of Radix Rehmanniae, 470 parts of Rhizoma Acori Graminei, 300 parts of Radix Polygalaes and Herba Pogostemonis.
3. the preparation method of medicine as claimed in claim 1 or 2 is characterized in that comprising the following steps:
(1) at first Rhizoma Acori Graminei in the described weight portion proportioning and Herba Pogostemonis are mixed, decoct with water, it is standby to collect volatile oil with the steam distillation extracting method, and it is standby to get filtrate A after water decoction filters;
(2) medicinal residues that obtain after described water decoction is filtered mix with surplus stock medicine in the described weight portion proportioning, decoct with water extraction more than 1 time, the merging decoction liquor, and B filters to get filtrate;
(3) merging filtrate A and liquor B and by macroporous resin, the reuse ethanol elution, collect that ethanol elution concentrates, after the drying dry extract;
(4) dry extract is pulverized the back and add the active component that described volatile oil just has been prepared into medicine;
(5) acceptable auxiliary on the active component adding pharmaceutics of described medicine is made dosage form pharmaceutically commonly used.
4. as the preparation method of medicine as described in the claim 3, it is characterized in that: decocting with water 4 times in (2) step merges 4 times decoction liquor; In (4) step described dry extract is added silicon dioxide and mix pulverizing in right amount, the also dry back of sieving adds the active component that described volatile oil just has been prepared into medicine.
5. as the preparation method of medicine as described in the claim 4, wherein add silicon dioxide and mix and pulverize the back and cross 60 mesh sieves, and dry under 65～70 ℃ of temperature, make its dried moisture in 10%.
6. the preparation method of the described medicine of claim 3, wherein said volatile oil are in volatile oil: betacyclodextrin: water=ratio of 1: 5: 50 is mixed the betacyclodextrin clathrate of the volatile oil that obtains behind the parcel.
7. the preparation method of the described medicine of claim 6, the step of wherein said mixing parcel is: at first the volatile oil in the described proportioning is added an amount of mixing of dehydrated alcohol; To be cooled to 75～55 ℃ again after betacyclodextrin in the described proportioning and the dissolving of water Hybrid Heating then, and place on the constant temperature blender with magnetic force, splash into the alcoholic solution of described volatile oil gradually, stirred 1 hour, be cooled to room temperature in 75～55 ℃ of constant temperature; Hid 24 hours in 4～5 ℃ refrigerator and cooled at last, filter, after 50 ℃ of dryings and pulverizing, obtain the betacyclodextrin clathrate of volatile oil.
8. the preparation method of the described medicine of claim 3, it is characterized in that: the described water vapour distillation time is 2～6 hours; Described decocting with water when extracting 4 times, the 1st, 2 time decocts amount of water is 12 times of amounts of raw medicinal herbs, the 3rd, 4 time decocts amount of water is 8 times of amounts of raw medicinal herbs, decocts 40 minutes at every turn; Described macroporous resin is D
101The type macroporous resin; Described is 65～85% with the concentration of alcohol in the ethanol elution macroporous resin; Described dry extract is 1.0～2.20 T=60 ℃ relative density.
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| CN102657775B (en) * | 2012-03-21 | 2013-06-26 | 张金响 | Medicament composition for treating depression |
| CN104606636B (en) * | 2015-01-29 | 2018-03-06 | 北京中医药大学东方医院 | A kind of Chinese medicine composition for treating depression and preparation method thereof |
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Non-Patent Citations (2)
| Title |
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| 王艳旭,许笃聪.中风后抑郁症的中医药治疗进展.河南中医36 3.2006,36(3),79-80. |
| 王艳旭,许笃聪.中风后抑郁症的中医药治疗进展.河南中医36 3.2006,36(3),79-80. * |
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