CN105169395B - A kind of compound preparation for being used to treat depression - Google Patents
A kind of compound preparation for being used to treat depression Download PDFInfo
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- CN105169395B CN105169395B CN201510579797.XA CN201510579797A CN105169395B CN 105169395 B CN105169395 B CN 105169395B CN 201510579797 A CN201510579797 A CN 201510579797A CN 105169395 B CN105169395 B CN 105169395B
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- chlorogenic acid
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Abstract
The present invention provides a kind of for treating the compound preparation of depression, belong to pharmaceutical technology field, the active ingredient of compound preparation includes：Common antidepressants and chlorogenic acid；The common antidepressants are 5 serotonin reuptake inhibitors or tricyclic antidepressants and heterocyclic antidepressants.Compound preparation provided by the present invention not only reduces the side effect of common antidepressants, and also improves curative effect by the way that chlorogenic acid using common antidepressants and chlorogenic acid as active ingredient, is made to generate synergistic effect with common antidepressants.
Description
Technical field
The present invention relates to pharmaceutical technology field, in particular to a kind of compound preparation for being used to treat depression.
Background technology
Depression is a kind of very universal disease, and some periods have in various degree about 10% people in life in crowd
Depression, and patients with depression often have serious introgression, according to investigations the U.S. commit suiside per year over 30000 people, and
Depression is considered as a principal element.
Currently used antidepressants have a serotonin reuptake inhibitor, tricyclic antidepressants and heterocyclic antidepressants etc., but
It is that the generally existing clinical treatment cycle is long, the defects of the asynchronous and serious side effect that target effect improves with symptom.
Chlorogenic acid（Chlorogenic acid）It is by caffeic acid（Caffeic acid）With chinic acid（Quinic acid）
The depside of composition, different name are chlorogenic acid, the entitled 3-O- caffeoyls Kui acid of chemistry（3-O-caffeoylquinic
acid）, it is a kind of benzene-like compounds that plant generates during aerobic respiration through shikimic acid pathway.
Chlorogenic acid has been widely used in the multiple fields such as food, health products, cosmetics and drug, such as：Cardiovascular protection
Effect, antioxidation, uvioresistant and radiation resistance, anti-mutagenesis and antitumaous effect, antibacterial action, antivirus action, drop
Blood lipid and reducing blood sugar effect, immunoregulation effect etc., but other effects of chlorogenic acid also need to further research and explore.
The content of the invention
To solve the above-mentioned problems, it is an object of the invention to provide a kind of for treating the compound preparation of depression, with
The side effect of common antidepressants is reduced, and improves its curative effect.
The present invention is achieved in the following ways：
A kind of compound formulation for being used to treat depression, the active ingredient of compound formulation include：Common antidepressants and
Chlorogenic acid；The common antidepressants are serotonin reuptake inhibitor or tricyclic antidepressants and heterocyclic antidepressants.
Further, the serotonin reuptake inhibitor for Prozac, Paxil, Sertraline, Fluvoxamine or
Citalopram.
Further, the tricyclic antidepressants and heterocyclic antidepressants are imipramine, amitriptyline or chlorimipramine.
The present invention is using common antidepressants and above-mentioned compound preparation carries out mouse forced swimming test respectively and mouse is hanged
Tail is tested, to study its antidepressant effect.The motionless of the mouse for the experimental group for having injected above-mentioned compound preparation is found through experiments that
Time is respectively less than the experimental group for having injected common antidepressants, and therefore, chlorogenic acid and common antidepressants can generate collaboration and resist
Depression effect, makes the antidepressant effect effect of above-mentioned compound preparation be better than the common antidepressants of exclusive use.
Common antidepressants are playing antidepressant while can also generate side effect, and therefore, the present invention is using common anti-
Depressant drug and above-mentioned compound preparation have carried out the test experiments of spontaneous activity in mice respectively, to study it to spontaneous activity in mice
It influences and has without side-effects.It is found through experiments that, has injected the Assay of spontaneous activity of the mouse of the experimental group of above-mentioned compound preparation
It is greater than the experimental group for having injected common antidepressants with standing behavior number, and it is substantially identical with the number of control group, therefore,
Above-mentioned compound preparation has no significant effect spontaneous activity in mice, and side effect will not be generated while antidepressant effect is played.
Further, the mass ratio of the common antimelancholic and chlorogenic acid is 1~4：1.
Further, the mass ratio of the common antimelancholic and chlorogenic acid is 2：1.
The mass ratio of common antidepressants and chlorogenic acid in above-mentioned compound preparation is 1~4:1, it is preferably 2:1.
Beneficial effects of the present invention：
Compound preparation provided by the present invention is by using common antidepressants and chlorogenic acid as active ingredient, making chlorogenic acid
Synergistic effect is generated with common antidepressants, the side effect of common antidepressants is not only reduced, and also improves treatment
Effect.
Specific embodiment
Embodiment 1
The collaboration antidepressant effect of chlorogenic acid and imipramine
1st, experiment material
ICR mouse, half male and half female, 20 ± 2g of weight.Rearing conditions：Air-conditioned room, 18-24 DEG C of temperature, relative humidity
70%。
2nd, experimental method
（1）Animal packet：ICR mouse 50 are only randomly divided into 5 groups, every group 10.
Chlorogenic acid group：Chlorogenic acid, successive administration 14 days are given in intraperitoneal injection.
Imipramine group：Imipramine, successive administration 14 days are given in intraperitoneal injection.
Chlorogenic acid and imipramine drug combination group（Mass ratio is 1:1）：It is first injected intraperitoneally and gives chlorogenic acid, abdomen after 30min
Imipramine is given in chamber injection；Successive administration 14 days.
Chlorogenic acid and imipramine drug combination group（Mass ratio is 1:2）：It is first injected intraperitoneally and gives chlorogenic acid, abdomen after 30min
Imipramine is given in chamber injection；Successive administration 14 days.
Control group：Give isometric physiological saline, successive administration 14 days.
（2）Experimental method：Using the antidepressant effect of mouse forced swimming test research drug.Before official testing for 24 hours, will
Mouse is placed in the glass jar of depth of water 10cm, and 24 DEG C of water temperature forces swimming instruction 15min.Then each group is administered, 30min
Mouse is placed in the glass jar of depth of water 10cm again afterwards and forces swimming 6min, observes and records the trip of mouse in last 4 minutes
It swims the dead time（It is floating to remain stationary as in water or when mild action keeps that head floats on the surface when mouse stops struggling
Between）.Influence result of each group drug to the non-swimming time of mouse is as shown in table 1 below（Note：Compared with the control, statistics is general
Rate P<0.05, there is statistical significance）.
| Grouping | Non-swimming time（s） |
| Control group | 156.5±6.2 |
| Imipramine group | 96.2±2.4 |
| Chlorogenic acid group | 102.8±8.5 |
| Chlorogenic acid and imipramine drug combination group（Mass ratio is 1:1） | 96.7±4.3 |
| Chlorogenic acid and imipramine drug combination group（Mass ratio is 1:2） | 50.7±1.9 |
Table 1
Judge index using mouse forced swimming test technique study antidepressants is the non-swimming time of mouse, small
The non-swimming time of mouse is shorter, and the antidepressant effect of antidepressants is stronger.
It is shown according to the experimental result of table 1, compared with the control group, chlorogenic acid group, imipramine group, chlorogenic acid and imipramine connection
The non-swimming time of mouse can significantly be reduced by sharing medicine group, illustrate imipramine, chlorogenic acid and using chlorogenic acid and
The compound preparation of imipramine drug combination is respectively provided with significant antidepressant effect.And chlorogenic acid and imipramine drug combination group
Non-swimming time is respectively less than chlorogenic acid group and imipramine group, therefore illustrates using compound preparation made of chlorogenic acid and imipramine
Antidepressant effect be better than the chlorogenic acid and imipramine of exclusive use.Especially mass ratio is 1:2 chlorogenic acid and imipramine
The non-swimming time of drug combination group will be significantly less than chlorogenic acid group, imipramine group and mass ratio for 1:1 chlorogenic acid and
Therefore imipramine drug combination group, uses mass ratio as 1:The antidepressant effect of compound preparation made of 2 can be shown more preferably
Antidepressant effect.
Embodiment 2
The influence of chlorogenic acid and compound preparation to spontaneous activity in mice
1st, experiment material
ICR mouse, half male and half female, 20 ± 2g of weight.Rearing conditions：Air-conditioned room, 18-24 DEG C of temperature, relative humidity
70%。
2nd, experimental method
（1）Animal packet：ICR mouse 50 are only randomly divided into 5 groups, every group 10.
Chlorogenic acid group：Chlorogenic acid, successive administration 14 days are given in intraperitoneal injection.
Imipramine group：Imipramine, successive administration 14 days are given in intraperitoneal injection.
Chlorogenic acid and imipramine drug combination group（Mass ratio is 1:1）：It is first injected intraperitoneally and gives chlorogenic acid, abdomen after 30min
Imipramine is given in chamber injection；Successive administration 14 days.
Chlorogenic acid and imipramine drug combination group（Mass ratio is 1:2）：It is first injected intraperitoneally and gives chlorogenic acid, abdomen after 30min
Imipramine is given in chamber injection；Successive administration 14 days.
Control group：Give isometric physiological saline, successive administration 14 days.
（2）Experimental method：The test experiments of spontaneous activity in mice are tested using mouse autonomic activities tester.In experiment just
Formula start before for 24 hours, 1h and 30min be administered respectively to each group mouse, test the measure that mouse is placed in after formal start tester
Interior adapts it to 5min, then records the number of activities of mouse and standing number in 20min.Each group drug is spontaneous to mouse
Number of activities and the influence result of standing behavior number are as shown in table 2 below（Note：Compared with the control, statistics probability P<0.05, tool
It is statistically significant）.
| Grouping | Assay of spontaneous activity | Standing behavior number |
| Control group | 403.5±26.8 | 78.6±18.2 |
| Imipramine group | 237.8±23.5 | 17.8±3.5 |
| Chlorogenic acid group | 400.5±28.4 | 64.1±18.2 |
| Chlorogenic acid and imipramine drug combination group（Mass ratio is 1:1） | 410.7±34.3 | 69.4±14.9 |
| Chlorogenic acid and imipramine drug combination group（Mass ratio is 1:2） | 402.4±21.9 | 70.3±11.7 |
Table 2
Influence of the antidepressants to spontaneous activity in mice is judged respectively by Assay of spontaneous activity and standing behavior number.According to
The experimental result of table 2 shows, the number of chlorogenic acid group and the spontaneous activity of chlorogenic acid and the mouse of imipramine drug combination group with
Control group is essentially identical, and the Assay of spontaneous activity of the mouse of imipramine group significantly reduces；And it in the experiment of standing number, shows
Show essentially identical as a result, there was only the standing behavior number that imipramine group can significantly reduce mouse in experiment, and chlorogenic acid
Group is substantially identical with control group with the standing behavior number of chlorogenic acid and the mouse of imipramine drug combination group, therefore, illustrates third
Miaow piperazine can also generate calm side effect while antidepressant effect is played, and chlorogenic acid combines use with chlorogenic acid and imipramine
Medicine will not generate calm side effect while antidepressant effect is played, so as to using compound made of chlorogenic acid and imipramine
Preparation can reduce the side effect of imipramine.
Embodiment 3
The collaboration antidepressant effect of chlorogenic acid and Prozac
1st, experiment material
ICR mouse, half male and half female, 20 ± 2g of weight.Rearing conditions：Air-conditioned room, 18-24 DEG C of temperature, relative humidity
70%。
2nd, experimental method
（1）Animal packet：ICR mouse 50 are only randomly divided into 5 groups, every group 10.
Chlorogenic acid group：Chlorogenic acid, successive administration 14 days are given in intraperitoneal injection.
Prozac group：Prozac, successive administration 14 days are given in intraperitoneal injection.
Chlorogenic acid and Prozac drug combination group（Mass ratio is 1:2）：It is first injected intraperitoneally and gives chlorogenic acid, abdomen after 30min
Prozac is given in chamber injection；Successive administration 14 days.
Chlorogenic acid and Prozac drug combination group（Mass ratio is 1:4）：It is first injected intraperitoneally and gives chlorogenic acid, abdomen after 30min
Prozac is given in chamber injection；Successive administration 14 days.
Control group：Isometric physiological saline, successive administration 14 days are given in intraperitoneal injection.
（2）Experimental method：Using the antidepressant effect of Tail suspension test research drug.Tail suspension test is a kind of fast
The screening technique of the acute behavior effect of high-throughput antidepressant of speed.Experiment is formal start before for 24 hours, 1h and 30min distinguish
It is administered to each group mouse, tests and mousetail tip is fixed on liftoff 60cm high-altitude suspensions after formally starting, and record 6min
The outstanding tail dead time of interior mouse（Mouse hangs afterbody in liftoff certain altitude, and mouse can be transformed into motionless shape from motion state
State）.Each group drug is as shown in table 3 below to the influence result of the outstanding tail dead time of Tail suspension test（Note：Compared with the control,
Statistics probability P<0.05, there is statistical significance）.
| Grouping | The outstanding tail dead time（s） |
| Control group | 218.5±26.2 |
| Prozac group | 100.3±12.4 |
| Chlorogenic acid group | 111.9±14.3 |
| Chlorogenic acid and Prozac drug combination group（Mass ratio is 1:2） | 67.3±8.1 |
| Chlorogenic acid and Prozac drug combination group（Mass ratio is 1:4） | 52.4±2.6 |
Table 3
Judge index using Tail suspension test technique study antidepressants is the outstanding tail dead time of mouse, mouse
The outstanding tail dead time is shorter, and the antidepressant effect of antidepressants is stronger.
It is shown according to the experimental result of table 3, compared with the control group, chlorogenic acid group, Prozac group, chlorogenic acid and Prozac connection
The outstanding tail dead time of mouse in Tail suspension test, i.e. Depressive behavior, therefore, explanation can be significantly decreased by sharing medicine group
Prozac, chlorogenic acid and significant antidepressant effect is respectively provided with using compound preparation made of chlorogenic acid and Prozac.But
It is outstanding tail dead time of the mouse of chlorogenic acid and Prozac drug combination group to be respectively less than chlorogenic acid group and Prozac group, therefore,
It is better than the chlorogenic acid and Prozac of exclusive use using the antidepressant effect of compound made of chlorogenic acid and Prozac, shows
Better antidepressant effect is shown.
Claims (3)
1. a kind of compound injection for being used to treat depression, which is characterized in that the active ingredient of compound preparation includes：It is common
Antidepressants and chlorogenic acid；The common antidepressants are tricyclic antidepressants and heterocyclic antidepressants；The common anti-suppression
The mass ratio of strongly fragrant medicine and chlorogenic acid is 1~4：1.
2. compound injection according to claim 1, which is characterized in that the tricyclic antidepressants and heterocyclic antidepressants are
Imipramine, amitriptyline or chlorimipramine.
3. compound injection according to claim 2, which is characterized in that the common antidepressants and chlorogenic acid
Mass ratio is 2：1.
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| IT202200000581A1 (en) * | 2022-01-17 | 2023-07-17 | Univ Degli Studi Di Verona | Quinic acid for use in the treatment of mood disorders |
| CN116999533A (en) * | 2023-08-16 | 2023-11-07 | 秦皇岛市山海关药业有限责任公司 | Heart-nourishing and pulse-activating granule, preparation method thereof and application thereof in antidepressant product |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102000334A (en) * | 2010-10-15 | 2011-04-06 | 北京大学 | Compound preparation for treating depression |
| CN103298354A (en) * | 2010-11-12 | 2013-09-11 | 雀巢产品技术援助有限公司 | Methods of improving mental or physical health conditions in an individual |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102000334A (en) * | 2010-10-15 | 2011-04-06 | 北京大学 | Compound preparation for treating depression |
| CN103298354A (en) * | 2010-11-12 | 2013-09-11 | 雀巢产品技术援助有限公司 | Methods of improving mental or physical health conditions in an individual |
Non-Patent Citations (1)
| Title |
|---|
| "Antidepressant-like effect of chlorogenic acid isolated from Artemisia capillaris Thunb.";Soo-Hyun Park etal;《Animal Cells and Systems》;20101210;第14卷(第4期);第235-259页 * |
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