CN1268343C - Compositions of asiatic centella and Hypericum perforatum extracts and its antidepressant action - Google Patents
Compositions of asiatic centella and Hypericum perforatum extracts and its antidepressant action Download PDFInfo
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- CN1268343C CN1268343C CN 200310108860 CN200310108860A CN1268343C CN 1268343 C CN1268343 C CN 1268343C CN 200310108860 CN200310108860 CN 200310108860 CN 200310108860 A CN200310108860 A CN 200310108860A CN 1268343 C CN1268343 C CN 1268343C
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- total glycosides
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Abstract
The present invention relates to a composition of asiaticoside and hypericum perforatum extracts and the use for preparing antidepressant medicine, which belongs to the medicinal technical field. The proportion of the asiaticoside and the hypericum perforatum extracts is 1 to 9: 9 to 1, and the optimal proportion is 1: 2 or 2: 1. Animal experiments improve that depression resistant function of the present invention is better than the single asiaticoside or the single hypericum perforatum extracts. Therefore, the composition of the present invention can be used for preparing antidepressant medicine.
Description
Technical field
The present invention relates to medical technical field, is Herba Centellae total glycosides and Herba Hyperici perforati extract compositions and the purposes that is used to prepare antidepressant drug thereof.
Background technology
Depression be with remarkable and persistent depressed, behavior is numb and pessimistic and worldweary be one group of disease of principal character.Its sickness rate height is called as " common cold " in the mental sickness, and simultaneously it still is serious threat human life's a disease.The medicine of treatment depression is mainly tricyclic antidepressants, Fourth Ring class, oxidase inhibitor at present, the 5-HT reuptake inhibitor, it represents medicine such as imipramine etc., these adverse effectes are more, as headache, dizziness, insomnia, drowsiness, nauseating, postural hypotension, tachycardia etc., limited its extensive use.
Domestic and international application in the Chinese medicine for the treatment of depression seldom at present.Herba Centellae Centella asiatica (L.) Urban is a umbellate form section plant, and world many countries and area also are used it as conventional medicament.In China south and South Asia region, among the people it is used as antidepressant drug.It is reported that Herba Centellae volatile oil has antidepressant effect, wherein Herba Centellae total glycosides is main effective ingredient, shows that through preliminary pharmacodynamics test it has antidepressant effect and (sees " The 2nd Army Medical College journal " 2002 for details, 23:1224-1226).Herba Hyperici perforati Hypericum perforatum L. has another name called Herba Hyperici Monogyni, is Guttiferae Hypericum herbaceos perennial, in the North America, all there is distribution in Europe, Asia.In recent years, studies have shown that Herba Hyperici perforati extract has anti-slight, moderate depressive patients effect, obtained using widely the America and Europe (see " external medical plant amedica fascicle " for details, 2001,16:238-240).But do not see that so far Herba Centellae total glycosides and Herba Hyperici perforati extract compositions are used for the report of depression.
Summary of the invention
The invention provides the compositions of a kind of Herba Centellae total glycosides and Herba Hyperici perforati extract.Through zoopery, the said composition antidepressant effect obviously is better than single Herba Centellae total glycosides or Herba Hyperici perforati extract, therefore can be used for preparing antidepressant medicine.
The prescription and the proportioning of the present composition are as follows:
Herba Centellae total glycosides 10～90%;
Herba Hyperici perforati extract 90～10%.
Best proportioning:
Herba Centellae total glycosides and Herba Hyperici perforati extract mass ratio 1: 2 or 2: 1.
Herba Centellae total glycosides and Herba Hyperici perforati extract preparation of compositions method:
1, preparation Herba Centellae total glycosides:
(1) preparation Herba Centellae extracting solution: the Herba Centellae medical material is adopted soak with ethanol, obtain the Herba Centellae extracting solution;
(2) purification:, after the distilled water eluting is removed impurity,, get the Herba Centellae total glycosides powder of purification after the drying with aquiferous ethanol eluting Herba Centellae total glycosides with saponin absorbent-type macroporous resin adsorption Herba Centellae extracting solution.Method sees patent of invention " novel preparation method of Herba Centellae total glycosides and new purposes thereof " (application number: 01113014.8) for details.
2, preparation Herba Hyperici perforati extract:
(1) preparation Herba Hyperici perforati extracting solution: Herba Hyperici perforati is adopted soak with ethanol, obtain the Herba Hyperici perforati extracting solution;
(2) purification: adopt macroporous resin adsorption Herba Hyperici perforati extracting solution,, get the Herba Hyperici perforati extract powder of purification again with aquiferous ethanol eluting after drying.Method sees " Chinese herbal medicine effective ingredients extracts and separates " (Shanghai science tech publishing house published in 1989) for details.
3, preparation Herba Centellae total glycosides and Herba Hyperici perforati extract compositions: with Herba Centellae total glycosides and Herba Hyperici perforati extract mixing, just can be used for preparing the antidepressant drug of different dosage form by said ratio.
The specific embodiment
Embodiment 1: the preparation Herba Centellae total glycosides
1 kilogram of exsiccant Herba Centellae was soaked 48 hours with 10 liter of 70% ethanol water, got soak after the filtration.Reclaim under reduced pressure routinely, obtain 2.5 liters of concentrated solutions, freezing precipitation, filtration under diminished pressure, filtrate is with the good D101 type saponin adsorption column of pretreatment (Tianjin positive day one-tenth company) purification, remove impurity with 2 liters of distilled water eluting earlier, reuse 70% ethanol elution is collected ethanol elution, behind the concentrating under reduced pressure, add ethyl acetate and make the asiatic centella total glycosidal crystalline, promptly get Herba Centellae total glycosides powder 21.5 grams after the drying.
Embodiment 2: the preparation Herba Hyperici perforati extract
1 kilogram of exsiccant Herba Hyperici perforati was soaked 48 hours with 15 liter of 60% ethanol water, get soak after the filtration.Reclaim under reduced pressure routinely, obtain 2.5 liters of concentrated solutions, freezing precipitation, filtration under diminished pressure, filtrate is removed impurity with 20% ethanol elution earlier with the good D101 type macroporous resin adsorption post of pretreatment (the positive day one-tenth company in Tianjin) purification, reuse 80% ethanol elution, collect ethanol elution, behind the concentrating under reduced pressure, promptly get Herba Hyperici perforati extract powder 30 grams after the drying.
Embodiment 3: preparation Herba Centellae total glycosides and Herba Hyperici perforati extract compositions
Herba Centellae total glycosides and Herba Hyperici perforati extract that embodiment 1 and 2 is made mix according to a certain percentage, get the present composition.
The A group: Herba Centellae total glycosides 30mg and Herba Hyperici perforati extract 60mg mixing get 1: 2 compositions of proportioning;
The B group: Herba Centellae total glycosides 60mg and Herba Hyperici perforati extract 30mg mixing get 2: 1 compositions of proportioning;
The C group: Herba Centellae total glycosides 30mg and Herba Hyperici perforati extract 30mg mixing get 1: 1 compositions of proportioning;
The D group: Herba Centellae total glycosides 90mg and Herba Hyperici perforati extract 10mg mixing get 9: 1 compositions of proportioning.
Herba Centellae total glycosides and Herba Hyperici perforati extract compositions are used for the treatment of the zoopery of depression
(1) forced swimming experiment and the experiment of antagonism reserpine
1, animal
Kunming mouse, male, body weight 20～24g, totally 120.Purchase in Chinese Academy of Sciences's Shanghai Experimental Animal Center (animal quality certification number: middle section Shanghai moving pipe word 99-003 number).Raise in cleaning level Animal House.
2, animal grouping and dosage
Mice is divided into 6 groups at random, every group of 10/cage group support, 4 groups of medicine groups, wherein 1-2 group feeding A group of the present invention and B organize mixture, and the 3rd, 4 group gives single Herba Centellae total glycosides or Herba Hyperici perforati extract and compositions contrast.Other establishes each 1 group of positive controls and blank group, and positive controls adopts antidepressants imipramine commonly used clinically.
1 group of medicine: 1: 2 mixture 90mg/kg of Herba Centellae total glycosides and Herba Hyperici perforati extract;
2 groups of medicines: 2: 1 mixture 90mg/kg of Herba Centellae total glycosides and Herba Hyperici perforati extract;
3 groups of medicines: Herba Centellae total glycosides 60mg/kg;
4 groups of medicines: Herba Hyperici perforati extract 60mg/kg;
Positive controls, imipramine 20mg/kg;
Said medicine all is dissolved in the 1ml water, then gastric infusion;
Blank group: 0.9% normal saline 1ml, gastric infusion.
3, zoopery
1) forced swimming experiment
With after mouse stomach administration half an hour, put into graduated cylinder (the high 20cm of 25 ± 1 ℃ of depth of water 10cm, water temperature, diameter 14cm) swimming in is measured mice and keeps the motionless time of swimming in 6 minutes back 4 minute, with the shortening of the dead time standard as judgement medicine antidepressant effect.Method sees " modern pharmacology experimental technique " (combined publication society of China Concord Medical Science University of Beijing Medical University published in 1998) for details.Experimental result sees Table 1.
Table 1 mice is to forced swimming dead time statistical table (x ± s)
| Group | Number of animals (only) | Non-swimming time (second) |
| 4 groups of 3 groups of medicines of 2 groups of medicines of 1 group of medicine of blank group positive controls medicine | 10 10 10 10 10 10 | 138.0±37.5 67.9±21.0 ** 31.3±27.3 ** 45.7±31.1 ** 118.8±21.4 90.4±23.5 * |
Compare * * P＜0.01, * P＜0.05 with the blank group
As can be seen from Table 1, Herba Centellae total glycosides and Herba Hyperici perforati extract compositions can significantly reduce the mice forced swimming dead time, 1 group, 2 groups curative effects of its Chinese medicine all significantly are better than the 3rd group of single Herba Centellae total glycosides and the 4th group of single Herba Hyperici perforati extract, also be better than positive control drug imipramine group, show that said composition has the effect of significant control animal depression.
2) antagonism reserpine experiment
Each organizes the lumbar injection 5mg/kg of mice elder generation reserpine, irritates stomach again and gives medicine or normal saline (contrast), and animal grouping and dosage are the same.Measure the anus temperature with anus thermometre after 4 hours, relatively the difference of administration group and control animals anus temperature.Method sees " modern pharmacology experimental technique " for details.Experimental result sees Table 2.
Table 2 mice reduces statistical table (x ± s) to reserpine induction body temperature
| Group | Number of animals (only) | Mice anus temperature (℃) |
| 4 groups of 3 groups of medicines of 2 groups of medicines of 1 group of medicine of blank group positive controls medicine | 10 10 10 10 10 10 | 36.36±0.42 37.17±0.44 ** 36.89±0.42 * 36.86±0.37 * 36.31±0.33 36.34±0.37 |
Compare * * P＜0.01, * P＜0.05 with the blank group
By table 2 result as can be seen, 1 group, the 2 groups all significantly body temperature of antagonism reserpine induction reductions of medicine, curative effect all significantly is better than the 3rd group of single Herba Centellae total glycosides and the 4th group of single Herba Hyperici perforati extract, shows that said composition has the effect of significant control animal depression.
(2) the present invention activates the control experiment of thing depression to the stress stimulation of long-term not precognition
1, animal
The SD rat, male, body weight 280～320 grams, totally 40.Purchase Shanghai Experimental Animal Center in the Chinese Academy of Sciences.(the animal quality certification number: middle section Shanghai moving pipe word 99-003 number).Raise in cleaning level Animal House.
2, animal grouping and dosage
Mice is divided into 5 groups at random, every group of 8/cage group support, 2 groups of medicine groups, feeding A group of the present invention and B group mixture.Other establishes each 1 group of positive controls, model group and blank group, and positive controls adopts antidepressants imipramine commonly used clinically.
1 group of medicine: 1: 2 mixture 90mg/kg of Herba Centellae total glycosides and Herba Hyperici perforati extract;
2 groups of medicines: 2: 1 mixture 90mg/kg of Herba Centellae total glycosides and Herba Hyperici perforati extract;
Positive controls: imipramine 20mg/kg;
Said medicine all is dissolved in the 1ml water, then gastric infusion;
Model group, blank group: 0.9% normal saline 1ml, gastric infusion.
3, zoopery
Spacious case activeness experiment (open field test) preceding 1 day respectively in stimulation, post-stimulatory the 7th day, 14 days, 21 days 19:00～22:30, it is that the cylinder that black, bottom surface are made up of 25 equal grids of area opens in the case that laboratory animal is placed high 40cm, diameter 80cm, perisporium, about 60 watts of intensity of illumination, indoor sound insulation, the record animal behavior, each minute is 3 minutes, to pass through bottom surface grid piece number is that horizontal anomalous movement score, upright number of times are vertical activity score, and the record defecation frequency, every animal only carries out behavior determination one time.Method sees " modern pharmacology experimental technique " for details.Experimental result sees Table 3, table 4.
Table 3 do not predict for a long time stress stimulation cause depression rat horizontal movement number of times statistical table (x ± s, n=8)
| Group | Stimulated preceding 1 day | Stimulated back 7 days | Stimulated back 14 days | Stimulated back 21 days |
| 2 groups of 1 group of medicines of blank group model group positive controls medicine | 75.7±12.2 69.4±9.2 61.8±13.2 68.8±11.2 81.3±5.5 | 73.9±15.0 71.1±9.1 64.3±13.9 65.3±9.7 74.9±10.6 | 64.6±13.5 65.3±10.4 43.0±11.6 63.4±8.5 71.6±10.7 | 55.75±15.2 34.4±9.8 70±13.0 ** 65.1±15.2 ** 104.8±28.8 ** |
Compare * * P＜0.01, * P＜0.05 with model group
Table 4 do not predict for a long time stress stimulation cause the depression rat move both vertically the number of times statistical table (x ± s, n=8)
| Group | Stimulated preceding 1 day | Stimulated back 7 days | Stimulated back 14 days | Stimulated back 21 days |
| 2 groups of 1 group of medicines of blank group model group positive controls medicine | 19.2±2.9 15.0±4.2 12.7±4.7 17.3±3.1 13.6±3.0 | 18.2±4.7 ** 5.3±1.8 3.8±5.0 14.6±3.9 ** 7.6±3.6 | 14.4±2.4 ** 4±2.7 9.7±3.4 ** 12.8±6.1 * 14.3±5.5 ** | 17.5±4.4 ** 3.0±2.0 13.7±4.3 ** 17.3±4.9 ** 15.2±3.9 ** |
Compare * * P＜0.01, * P＜0.05 with model group
By table 3, table 4 result as can be seen, Herba Centellae total glycosides all can significantly increase chronic stress with Herba Hyperici perforati extract with the compositions of mixing composition in 1: 2 or 2: 1 and stimulate horizontal movement that activates thing depression rat and the number of times that moves both vertically, the positive control drug imipramine that is better than evident in efficacy shows that said composition has the effect of significant control animal depression.
Claims (2)
1. Herba Centellae total glycosides and Herba Hyperici perforati extract compositions, preparation method is as follows:
(1) preparation Herba Centellae total glycosides: the Herba Centellae medical material is adopted soak with ethanol, obtain the Herba Centellae extracting solution; With saponin absorbent-type macroporous resin adsorption Herba Centellae extracting solution, after the distilled water eluting is removed impurity,, get the Herba Centellae total glycosides powder of purification with aquiferous ethanol eluting Herba Centellae total glycosides;
(2) preparation Herba Hyperici perforati extract: Herba Hyperici perforati is adopted soak with ethanol, obtain the Herba Hyperici perforati extracting solution; Adopt macroporous resin adsorption Herba Hyperici perforati extracting solution,, get the Herba Hyperici perforati extract powder of purification again with aquiferous ethanol eluting after drying;
(3) be 1: 2 or 2: 1 mixings by Herba Centellae total glycosides and Herba Hyperici perforati extract mass ratio.
2. described Herba Centellae total glycosides of claim 1 and the Herba Hyperici perforati extract compositions application in the preparation antidepressant drug.
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| CN109331070A (en) * | 2018-12-24 | 2019-02-15 | 雅安太时生物科技股份有限公司 | A kind of antidepressant preparation and preparation method thereof |
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Granted publication date: 20060809 Termination date: 20111125 |