Summary of the invention
The object of this invention is to provide the new purposes of Caulis et Folium Lactucae sativae glycosides B.
The invention provides the application of Caulis et Folium Lactucae sativae glycosides B in the medicine of preparation prevention and Cure of depression.
Application provided by the invention, Caulis et Folium Lactucae sativae glycosides B intends quantity and is: 100-400mg/d.
Described medicine is the preparation that contains Caulis et Folium Lactucae sativae glycosides B.
Described preparation is made up separately of Caulis et Folium Lactucae sativae glycosides B or is made up of Caulis et Folium Lactucae sativae glycosides B and pharmaceutically acceptable carrier.
Described preparation is tablet, capsule, pill, oral liquid, granule or injection, and described tablet is conventional tablet or sublingual lozenge.
Described pharmaceutically acceptable carrier refers to the pharmaceutical carrier of pharmaceutical field routine, is selected from one or more in filler, binding agent, disintegrating agent, lubricant, solubilizing agent, suspending agent, wetting agent, pigment, essence, solvent, surfactant or correctives.
Described filler is selected from starch, pregelatinized Starch, dextrin, glucose, sucrose, lactose, lactose, microcrystalline Cellulose, mannitol, sorbitol or xylitol, preferably sorbitol, microcrystalline Cellulose, lactose or pregelatinized Starch;
Described disintegrating agent is selected from cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium or starch, preferably polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose or carboxymethyl starch sodium;
Described lubricant is selected from magnesium stearate, Pulvis Talci, micropowder silica gel, PEG4000, PEG6000 or sodium laurylsulfate, preferably magnesium stearate, Pulvis Talci;
Described binding agent is selected from sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, polyvidone, starch slurry, sucrose, Icing Sugar, rubber cement, gelatin or Polyethylene Glycol, preferably hydroxypropyl methylcellulose, polyvidone;
Described solubilizing agent is selected from sodium hydroxide, potassium hydroxide, sodium bicarbonate, meglumine, 1B or L-arginine, preferably sodium hydroxide, meglumine;
Described suspending agent is selected from micropowder silica gel, Cera Flava, cellulose or solid polyethylene glycol;
Described wetting agent is selected from glycerol, tween 80, ethyoxyl castor oil hydrogenated or lecithin;
Described solvent is selected from ethanol, liquid polyethylene glycol, isopropyl alcohol, tween 80, glycerol, propylene glycol or vegetable oil, and described vegetable oil is selected from soybean oil, Oleum Ricini, Oleum Arachidis hypogaeae semen, mediation wet goods;
Described surfactant is selected from smooth or Polysorbate (tween) of dodecylbenzene sodium sulfonate, stearic acid, Pluronic F68, fatty acid Pyrusussuriensis etc.;
Described correctives is selected from aspartame, Sucralose, essence, steviosin, acesulfame potassium, citric acid or saccharin sodium.
The new purposes of Caulis et Folium Lactucae sativae glycosides provided by the invention has the following advantages:
1, the invention provides the new purposes of Caulis et Folium Lactucae sativae glycosides B, for the control of depression, for patients with depression has brought new medicament selection;
2, this effect of drugs significantly, have no side effect;
3, good water solubility, is converted into clinical medicine easy, has a good application prospect;
4, experimental result prompting: Caulis et Folium Lactucae sativae glycosides B can increase the body weight of depression mice, increase its exercise performance, extend its swimming time, and improve its partially having a liking for sucrose water, more than effect all presents dose-dependence, and its effect is suitable with conventional clinically antidepressant fluoxetine effect, prompting Caulis et Folium Lactucae sativae glycosides B has therapeutical effect to depression; Caulis et Folium Lactucae sativae glycosides B preventive use can significantly reduce the mortality rate of depression mice, increases its body weight and exercise performance, extends animal swimming time, and prompting Caulis et Folium Lactucae sativae glycosides B has good preventive effect to depression.
Result shows: Caulis et Folium Lactucae sativae glycosides B has obvious prevention and therapeutic effect to the mental depression disease of bringing out due to a variety of causes.
The specific embodiment
Following examples are used for illustrating the present invention, but are not used for limiting the scope of the invention.
Embodiment 1: the therapeutical effect of Caulis et Folium Lactucae sativae glycosides B to mice depression
1, laboratory animal: 80 of male mouse of kunming, body weight 20-22g, purchased from Zhengzhou University's Experimental Animal Center.
2, experiment reagent and instrument:
The preparation of pharmaceutical college of Caulis et Folium Lactucae sativae glycosides B(Xinxiang College of Medical Science, purity is greater than 95%), fluoxetine Hydrochloride (Li Lai Suzhou pharmaceutical Co. Ltd), swimming pool, the spacious case of OpenField.
3, experiment grouping and experimental technique:
Before 80 mouse experiments, raise 1 week by illumination in 12 hours, 12 hours unglazed adaptabilities that shine, then at random using 10 mices as Normal group: point two cages are gregarious raises, 5, every cage.Normally give as required feedstuff and drinking-water, do not accept any stimulation.The modeling according to the methods below of all the other mices, filters out 50 successful mices of modeling after 21 days, be divided at random 5 groups, 10 every group.
The single cage of mice is fed, and accept seven kinds of different chronic stresses stimulates simultaneously.Comprise: the sleep deprivation environment that throws light on all night, fasting (24h), prohibits water (24h), frozen water swimming (4 ℃, 5min), hot water swimming (40 ℃, 5min), folder tail (2min), outstanding tail (3min).Every day a kind of random arrangement, the discontinuous appearance of homologous stimulus, experiment 28d in average every kind of stimulation be used 4 times, make mice can not expect by occur stimulation.While stimulating 21d, the successful mice of modeling is divided into following 5 groups:
Depressed group (model group): in experiment 28d, this group mice respectively single cage is fed, and accept various chronic stress stimulation, after 21d, every morning 8:00, according to 0.1ml/10g intraperitoneal injection of saline, injects 7 days continuously.
Fluoxetine Hydrochloride group (positive controls): feeding environment and stimulation mode are with depressed group, and every morning 8:00 is according to the medicine 0.5ml of 35 μ g/10g gavage distilled waters dissolvings, continuous use 7 days;
Caulis et Folium Lactucae sativae glycosides B low dose group: feeding environment and stimulation mode are with depressed group, and after 21 days, every morning 8:00 is according to the Caulis et Folium Lactucae sativae glycosides B0.5ml of 12.5 μ g/10g lumbar injection distilled waters dissolvings, continuous use 7 days;
Agent group in Caulis et Folium Lactucae sativae glycosides B: feeding environment and stimulation mode are with depressed group, and after 21 days, every morning 8:00 is according to the Caulis et Folium Lactucae sativae glycosides B0.5ml of 25 μ g/10g lumbar injection sterilizing distilled waters dissolvings, continuous use 7 days;
Caulis et Folium Lactucae sativae glycosides B high dose group: feeding environment and stimulation mode are with depressed group, and after 21 days, every morning 8:00 is according to the medicine 0.5ml of 50 μ g/10g lumbar injection sterilizing distilled waters dissolvings, continuous use 7 days.
During above-mentioned fluoxetine Hydrochloride group and the administration of the basic, normal, high dosage group of Caulis et Folium Lactucae sativae glycosides B, still continuing stimulates.
4, detect index and method:
4.1 body weight: before every morning administration, weigh in electronic scale, and record.
4.2 wilderness (open-field) experiment: the spacious each 50cm of case length, black is all painted in the inwall of case and bottom surface, bottom surface is divided into 25 grids that area equates, mice is placed in the middle of spacious case, to pass through the number of squares of bottom surface as the score of horizontal movement (three-jaw strides into above), leave casing as upright take two upper limb, observe mouse movement situation, minute is 5min.
4.3 sucrose solution consumption experiments: mice is prohibited after water at every turn, measures 1% sucrose water degree of having a liking for partially in every treated animal 12h.Sucrose degree of having a liking for partially=sucrose water consumption/(sucrose water consumption+distilled water consumption) × 100%.
4.4 forced swimmings experiments: carry out forced swimming experiment on the 21st day at chronic stress.Mice is put respectively into 15 ℃ of water temperatures, in the glass jar of depth of water 15cm, make mouse hind leg can not lean on glass jar bottom support health, every mice is swum 5min in advance, observes the swimming behavior of 5min after 24h, records dead time and swimming time.
5, statistical procedures: application SPSSl6.0 statistical software is to data analysis.Measurement data data with
represent.Significance test application variance analysis (F check) between many group means, uses significance test (t check) between two groups of means.
6, testing result
6.1 body weight: result is as shown in table 1
Table 1: the impact of Caulis et Folium Lactucae sativae glycosides B on depression Mouse Weight (
n=10)
| Group |
Dosage (μ g/10g) |
Body weight (g) |
| Normal group |
- |
30.27±3.14 |
| Depressed group |
- |
24.16±2.87
** |
| Caulis et Folium Lactucae sativae glycosides B low dose group |
12.5 |
27.36±0.15
△ |
| Dosage group in Caulis et Folium Lactucae sativae glycosides B |
25 |
29.80±1.27
△△ |
| Caulis et Folium Lactucae sativae glycosides B high dose group |
50 |
32.10±1.59
△△ |
| Fluoxetine Hydrochloride group |
35 |
29.83±0.94
△△ |
Note: compared with Normal group
*p<0.01, compared with depressed group
△p<0.05,
△ △p<0.01
Table 1 result shows: compared with Normal group, depressed group body weight significantly reduces, and difference has statistical significance (P<0.01); Compared with depressed group, the each dosage group of Caulis et Folium Lactucae sativae glycosides B and fluoxetine group body weight all obviously increase, and difference has statistical significance (P<0.05, P<0.01).Each dosage group no difference of science of statistics compared with fluoxetine group.
Results suggest: Caulis et Folium Lactucae sativae glycosides B can increase the body weight of depressed mice, and this effect notable difference compared with fluoxetine.
6.2 wilderness experimental results: as shown in table 2
Table 2: the impact of Caulis et Folium Lactucae sativae glycosides B on depression mice wilderness experimental result (
n=10)
| Group |
Dosage (μ g/10g) |
Horizontal movement number of times |
Upright number of times |
| Normal group |
- |
28.75±2.10 |
13.25±1.57 |
| Depressed group |
- |
16.94±1.32
** |
8.36±1.45
** |
| Caulis et Folium Lactucae sativae glycosides B low dose group |
12.5 |
19.30±3.52
△ |
9.26±0.18 |
| Dosage group in Caulis et Folium Lactucae sativae glycosides B |
25 |
26.31±3.40
△△ |
12.47±1.94
△△ |
| Caulis et Folium Lactucae sativae glycosides B high dose group |
50 |
32.00±4.21
△△ |
14.58±2.36
△△ |
| Fluoxetine Hydrochloride group |
35 |
30.78±5.06
△△ |
14.09±2.11
△△ |
Note: compared with Normal group
*p<0.01, compared with depressed group
△p<0.05,
△ △p<0.01
Table 2 result shows: compared with Normal group, depressed group horizontal movement number of times and upright number of times all significantly reduce (P<0.01); Compared with depressed group, the each dosage group of Caulis et Folium Lactucae sativae glycosides B all can significantly increase its horizontal movement number of times, Caulis et Folium Lactucae sativae glycosides B25 μ g/10g dosage group and 50 μ g/10g dosage groups can significantly increase the upright number of times of depressed mice, and Caulis et Folium Lactucae sativae glycosides B presents dose dependent to the impact of mice horizontal movement number of times and upright number of times.Caulis et Folium Lactucae sativae glycosides B50 μ g/10g dosage group and fluoxetine group are suitable to the influence of wilderness experiment.
Results suggest: Caulis et Folium Lactucae sativae glycosides B has the effect that increases depressed mouse movement performance.
6.3 sucrose solution consume experimental result: as shown in table 3.
Table 3: Caulis et Folium Lactucae sativae glycosides B on the impact of degree of having a liking for partially of depressed mice sucrose (
n=10)
| Group |
Dosage (μ g/10g) |
Sucrose is degree of having a liking for (%) partially |
| Normal group |
- |
98.25±2.46 |
| Depressed group |
- |
67.33±5.04
** |
| Caulis et Folium Lactucae sativae glycosides B low dose group |
12.5 |
81.49±7.06
△△ |
| Dosage group in Caulis et Folium Lactucae sativae glycosides B |
25 |
87.26±9.52
△△ |
| Caulis et Folium Lactucae sativae glycosides B high dose group |
50 |
95.23±4.37
△△ |
| Fluoxetine group |
35 |
92.30±5.11
△△ |
?note: compared with Normal group
*p<0.01, compared with depressed group
△ △p<0.01
Table 3 result shows: compared with Normal group, depressed group sucrose partially degree of having a liking for significantly reduces (P<0.01), proves that depression model mice simulates successfully; Compared with depressed group, Caulis et Folium Lactucae sativae glycosides B12.5 μ g/10g group, Caulis et Folium Lactucae sativae glycosides B25 μ g/10g group and Caulis et Folium Lactucae sativae glycosides B50 μ g/10g group sucrose partially degree of having a liking for obviously increase, P<0.01, sucrose partially degree of having a liking for and drug dose presents certain dose-effect relationship, and the each dosage group of Caulis et Folium Lactucae sativae glycosides B on sucrose, the impact of degree of having a liking for is suitable with fluoxetine group partially.
6.4 forced swimming experimental results: as shown in table 4
Table 4: the impact of Caulis et Folium Lactucae sativae glycosides B on depression mice forced swimming experimental result (
n=10)
| Group |
Dosage (μ g/10g) |
Dead time (s) |
Swimming time (s) |
| Normal group |
- |
128.30±14.65 |
169.44±12.39 |
| Depressed group |
- |
181.37±10.22
* |
107.43±9.43
** |
| Caulis et Folium Lactucae sativae glycosides B low dose group |
12.5 |
164.31±13.42
△ |
129.57±2.16 |
| Dosage group in Caulis et Folium Lactucae sativae glycosides B |
25 |
136.31±3.40
△ |
142.35±10.85
△ |
| Caulis et Folium Lactucae sativae glycosides B high dose group |
50 |
129.07±4.21
△△ |
157.39±7.30
△△ |
| Fluoxetine group |
35 |
130.78±7.04
△△ |
166.02±23.18
△△ |
Note: compared with Normal group
*p<0.05,
*p<0.01, compared with depressed group
△p<0.05,
△ △p<0.01
Table 4 result shows: compared with Normal group, and depressed group mice non-swimming time significant prolongation (P<0.05), swimming time obviously shortens (P<0.05); The each dosage group of Caulis et Folium Lactucae sativae glycosides B and fluoxetine group all can shorten mice non-swimming time, Caulis et Folium Lactucae sativae glycosides B25 μ g/10g group, Caulis et Folium Lactucae sativae glycosides B50 μ g/10g group and fluoxetine group can extend mice swimming time, and Caulis et Folium Lactucae sativae glycosides B50 μ g/10g dosage group and fluoxetine group are suitable to depressed forced swimming time in mice influence.
Results suggest: Caulis et Folium Lactucae sativae glycosides B can extend depressed mice swimming time, shortens its non-swimming time.
Embodiment 2: the preventive effect of Caulis et Folium Lactucae sativae glycosides B to mice depression
1, laboratory animal: 50 of male mouse of kunming, body weight 20-22g, purchased from Zhengzhou University's Experimental Animal Center.
2, experiment reagent and instrument:
The preparation of pharmaceutical college of Caulis et Folium Lactucae sativae glycosides B(Xinxiang College of Medical Science, purity is greater than 95%), fluoxetine Hydrochloride (Li Lai Suzhou pharmaceutical Co. Ltd), swimming pool, the spacious case of OpenField.
3, experiment grouping and experimental technique:
Before 50 mouse experiments, raise 1 week according to adaptability by illumination in 12 hours, 12 hours are unglazed, then at random using 10 mices as Normal group, 20 as model group, and 20 as Caulis et Folium Lactucae sativae glycosides B prophylactic group.Normal control component two cages are gregarious raises, 5, every cage.Normally give as required feedstuff and drinking-water, do not accept any stimulation.The modeling according to the methods below of all the other mices:
The single cage of mice is fed, and accept seven kinds of different chronic stresses stimulates simultaneously.Comprise: the sleep deprivation environment that throws light on all night, fasting (24h), prohibits water (24h), frozen water swimming (4 ℃, 5min), hot water swimming (40 ℃, 5min), folder tail (2min), outstanding tail (3min).Every day a kind of random arrangement, the discontinuous appearance of homologous stimulus, experiment 21d in average every kind of stimulation be used 3 times, make mice can not expect by occur stimulation.
Model group: in experiment 21d, this group mice respectively single cage is fed, and accept various chronic stress stimulation, from accepting stimulation first day, every morning 8:00 is according to 0.1ml/10g intraperitoneal injection of saline.
Caulis et Folium Lactucae sativae glycosides B prophylactic group: feeding environment and stimulation mode, with depressed group, stimulate first day to start the Caulis et Folium Lactucae sativae glycosides B0.5ml that every morning 8:00 dissolves according to 25 μ g/10g lumbar injection sterilizing distilled waters, continuous use 21 days certainly;
4, detect index and method:
4.1 mortality rates: add up animal dead number of elements when experiment finished by 21 days, and calculate mortality rate.
4.2 body weight: before every morning administration, weigh in electronic scale, and record.
4.3 wilderness (open-field) experiment: the spacious each 50cm of case length, black is all painted in the inwall of case and bottom surface, bottom surface is divided into 25 grids that area equates, mice is placed in the middle of spacious case, to pass through the number of squares of bottom surface as the score of horizontal movement (three-jaw strides into above), leave casing as upright take two upper limb, observe mouse movement situation, minute is 5min.
4.4 forced swimmings experiments: carry out forced swimming experiment on the 22nd day at chronic stress.Mice is put respectively into 15 ℃ of water temperatures, in the glass jar of depth of water 15cm, make mouse hind leg can not lean on glass jar bottom support health, every mice is swum 5min in advance, observes the swimming behavior of 5min after 24h, records dead time and swimming time.
5, statistical procedures: application SPSSl6.0 statistical software is to data analysis.Measurement data data with
represent.Significance test application variance analysis (F check) between many group means, uses significance test (t check) between two groups of means.
6, testing result
6.1 mortality rates: result is as shown in table 5
Table 5: the impact of Caulis et Folium Lactucae sativae glycosides B on depression mouse death rate
| Group |
Dosage (μ g/10g) |
Dead number of elements |
Mortality rate (%) |
| Normal group |
- |
0 |
0 |
| Model group |
- |
8 |
40
** |
| Caulis et Folium Lactucae sativae glycosides B prophylactic group |
25 |
0 |
0
△△ |
Note: compared with Normal group
*p<0.01, compared with model group
Δ Δp<0.01
Table 5 result shows: compared with Normal group, model group mortality rate in modeling process is higher is 40%, and mouse death rate significance reduces (P<0.01), there was no significant difference compared with Normal group after the preventative injected in mice Caulis et Folium Lactucae sativae glycosides B of giving.
Results suggest: Caulis et Folium Lactucae sativae glycosides B can reduce the mortality rate of depression mice.
6.2 body weight: result is as shown in table 6
Table 6: the impact of Caulis et Folium Lactucae sativae glycosides B prophylactic on depression Mouse Weight
| Group |
Dosage (μ g/10g) |
Body weight (g) |
| Normal group |
- |
29.15±2.63 |
| Model group |
- |
22.40±3.81
* |
| Caulis et Folium Lactucae sativae glycosides B prophylactic group |
25 |
30.72±1.89
Δ |
Note: compared with Normal group
*p<0.05, compared with model group
Δp<0.05
Table 6 result shows: compared with Normal group, model group body weight significantly reduces, and difference has statistical significance (P<0.05); Compared with model group, Caulis et Folium Lactucae sativae glycosides B prophylactic group body weight all obviously increases, and difference has statistical significance (P<0.05)
Results suggest: Caulis et Folium Lactucae sativae glycosides B prophylactic can increase the body weight of depressed mice.
6.3 wilderness experimental results: as shown in table 7
Table 7: the impact of Caulis et Folium Lactucae sativae glycosides B preventive usage on depression mice wilderness experimental result
| Group |
Dosage (μ g/10g) |
Horizontal movement number of times |
Upright number of times |
| Normal group |
- |
26.35±1.04 |
12.60±1.33 |
| Model group |
- |
13.76±2.09
** |
7.19±0.85
** |
| Caulis et Folium Lactucae sativae glycosides B prophylactic group |
25 |
27.82±2.46
△△ |
13.55±1.94
△△ |
[0107]note: compared with Normal group
*p<0.01, compared with model group
△ △p<0.01
Table 7 result shows: compared with Normal group, model group horizontal movement number of times and upright number of times all significantly reduce, P<0.01; Compared with model group, Caulis et Folium Lactucae sativae glycosides B prophylactic group all can significantly increase its horizontal movement number of times and add and the upright number of times of mice.
Results suggest: Caulis et Folium Lactucae sativae glycosides B prophylactic has the effect that increases depressed mouse movement performance.
6.4 forced swimming experimental results: as shown in table 8
The impact of table 8 Caulis et Folium Lactucae sativae glycosides B preventive usage on depression mice forced swimming experimental result
| Group |
Dosage (μ g/10g) |
Dead time (s) |
Swimming time (s) |
| Normal group |
- |
119.87±6.43 |
171.20±9.35 |
| Model group |
- |
186.01±4.70
* |
96.22±7.05
** |
| Caulis et Folium Lactucae sativae glycosides B prophylactic group |
25 |
126.14±10.68
△ |
164.99±11.37
△△ |
Note: compared with Normal group
*p<0.05, compared with model group
△ △p<0.01
Table 8 result shows: compared with Normal group, model group mice non-swimming time extends, and swimming time shortens, P<0.05; Caulis et Folium Lactucae sativae glycosides B prophylactic group can shorten mice non-swimming time, and extends mice swimming time.
Results suggest: Caulis et Folium Lactucae sativae glycosides B prophylactic can extend depressed mice swimming time, shortens its non-swimming time.
The experimental summary of experimental example 1,2:
According to embodiment 1 experimental result, prompting Caulis et Folium Lactucae sativae glycosides B can increase the body weight of depression mice, increase its exercise performance, extend its swimming time, and improve its partially having a liking for sucrose water, more than effect all presents dose-dependence, and its effect is suitable with conventional clinically antidepressant fluoxetine effect, and prompting Caulis et Folium Lactucae sativae glycosides B has therapeutical effect to depression;
According to embodiment 2 experimental results, prompting Caulis et Folium Lactucae sativae glycosides B preventive use can significantly reduce the mortality rate of depression mice, increases its body weight and exercise performance, extends animal swimming time, and prompting Caulis et Folium Lactucae sativae glycosides B has good preventive effect to depression.
The above results and conclusion are to draw on the basis that uses various mildness Induced by Stimulation mice depressions, in view of this, Caulis et Folium Lactucae sativae glycosides B has obvious prevention and therapeutic effect to the mental depression disease of bringing out due to a variety of causes, the depression that other reasons is brought out is at present because the restriction of the aspects such as technological means temporarily cannot be passed judgment on, but according to current experimental result, its depressions that other reason is brought out of effect prompting such as the improvement of Caulis et Folium Lactucae sativae glycosides B to animal activity also have certain preventive and therapeutic effect.
Although, above use general explanation, the specific embodiment and test, the present invention is described in detail, on basis of the present invention, can make some modifications or improvements it, and this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.