CN115969947A - Application of nutrition-activating tablet in preparation of medicine for treating anxiety and depression co-disease, depression or anxiety - Google Patents
Application of nutrition-activating tablet in preparation of medicine for treating anxiety and depression co-disease, depression or anxiety Download PDFInfo
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- CN115969947A CN115969947A CN202310115992.1A CN202310115992A CN115969947A CN 115969947 A CN115969947 A CN 115969947A CN 202310115992 A CN202310115992 A CN 202310115992A CN 115969947 A CN115969947 A CN 115969947A
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Abstract
The invention provides application of a nutrient-regulating tablet in preparing a medicine for treating anxiety and depression co-disease, depression or anxiety. The sugar water preference degree of the mouse is reduced through a mouse model causing anxiety and depression co-morbidity by a chronic constraint stress model, so that the arm closing time of the elevated plus maze of the mouse is prolonged. The curative effect of the nutrient-containing tablet and the model mouse for treating the bipolar affective disorder by combining with the antidepressant medicament and the anti-bipolar affective disorder medicament is observed, and the treatment basis is provided for patients with the bipolar affective disorder, depression and anxiety.
Description
Technical Field
The invention belongs to the technical field of medicine research and development, and particularly relates to application of a nutrition tablet in preparation of a medicine for treating anxiety and depression co-disease, depression or anxiety.
Background
Bipolar Disorder (BD), also known as bipolar disorder, is a common group of mental disorders with both manic and depressive episodes (typical characteristics). At the time of a manic episode, the patient exhibits an abnormally elevated state; during the onset of depression, patients often show symptoms such as low mood and loss of pleasure. The clinical symptoms of the patients are complicated, and are manifested by repeated, alternate and irregular appearance of low or high mood, accompanied by disorder symptoms such as distraction, low rate, exaggeration, thinking and running, high reactivity, sleep reduction and speech increase. Anxiety, obsessive-compulsive disorder, substance abuse, and psychogenic symptoms such as hallucinations, delusions, or tenseness are also common. Clinical treatment of manic episodes in patients with acute mania or hypomania involves administering to the patient a drug which rapidly alleviates the manic symptoms, in patients with depressive episodes, and in the treatment of bipolar depression, which is prone to adverse effects, usually without the use of antidepressant drugs alone, if necessary in combination with mood stabilisers.
Disclosure of Invention
The invention mainly aims to solve the problems in the prior art and provides application of a nutrition tablet in preparation of a medicine for treating anxiety and depression co-morbid, depression or anxiety.
In order to achieve the purpose, the invention provides application of a nutrition tablet in preparing a medicine for treating anxiety and depression co-disease, depression or anxiety. Wherein, anxiety and depression are commonly encountered in patients with anxiety and depression disorder.
Preferably, the anxiety and depression co-morbid is bipolar affective disorder.
Preferably, the medicine for treating the anxiety symptom in the anxiety and depression co-morbid is prepared by changing the dosage of the nutrition tablet.
Preferably, the dosage of the nutrition tablet for preparing the medicine for treating the anxiety symptom in the anxiety and depression co-morbid is larger than that of the nutrition tablet for preparing the medicine for treating the depression symptom in the anxiety and depression co-morbid.
Preferably, the medicine for treating anxiety symptom and depression symptom in depression, anxiety neurosis or anxiety and depression co-morbid diseases is prepared by combining the dactyl tablet and the citalopram.
Preferably, the medicine for treating anxiety symptom in anxiety disorder or anxiety depression comorbidity is prepared by combining the nutrition tablet and lithium carbonate.
Drawings
FIG. 1 is a graph showing the results of the sugar water preference test of the mice after 14 days in example 1.
FIG. 2 is a graph showing the results of the sugar water preference test of mice 3 weeks after administration.
FIG. 3 is a graph showing the results of an elevated plus maze experiment in mice 3 weeks after administration.
Fig. 4 is a graph showing the results of the autonomic activity test of the mice 3 weeks after the administration.
Detailed Description
In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further described in the following combined with the specific embodiments.
The 'Danying tablet' is a medicine disclosed by Chinese invention patent CN 102008688A. At present, hospital preparations for medical insurance inclusion can be purchased in hospital prescriptions. The camping tablet is prepared by modern standard pharmaceutical technology, and the related information is as follows:
[ prescription ] zedoary turmeric oil 2.5ml red peony root 1000g raw rhubarb 1000g prepared into 1000 tablets
[ PROPERTIES ] film-coated tablets
[ Committee configuration Unit ] Shanghai Baolong pharmaceutical Co., ltd
[ PREPARATION ] pulverizing 100g of radix et rhizoma Rhei into fine powder and sieving (separately storing) except zedoary turmeric oil, decocting the rest materials with water twice, filtering, mixing filtrates, concentrating under reduced pressure to obtain extract with relative density of 1.33-1.36, drying until the water content is less than or equal to 5%, pulverizing the above dried extract into fine powder, adding pulverized and sieved radix et rhizoma Rhei fine powder and starch, mixing, granulating, and drying; diluting zedoary turmeric oil with appropriate amount of ethanol, spraying onto dried granule, mixing, adding appropriate amount of magnesium stearate, pressing into 1000 tablets, and coating.
The test article, lot number, of the run-sheet referred to in the following examples: 2005001, property: film-coated tablets, specification: 300 tablets/bottle 0.33 g/tablet, storage conditions: shading light and storing at 4 ℃; the manufacturer: shanghai mental health center.
The citalopram drug referred to in the following examples is escitalopram oxalate tablets, the manufacturer: lundbeck A/S, character: a white tablet; specification: 10mg; batch number: 2661728; storage conditions are as follows: shielded from light and stored at 4 ℃.
(note: escitalopram oxalate, chemical structure S (+) -1- (3-dimethylaminopropyl) -1- (4-fluorophenyl) -1, 3-dihydroisobenzofuran-5-carbonitrile oxalate, is a first-line antidepressant drug for the treatment of depression, belonging to the selective 5-hydroxytryptamine reuptake inhibition (SSRI)). The experimental purpose of the escitalopram tablets in this example is to act as a therapeutic gold standard and to combine with a dactylene tablet to compare the difference in therapeutic effect.
The lithium carbonate sustained release tablets related in the following examples are prepared by: jiangsu Enhua pharmaceutical industry, property: white tablets; specification: 0.3g; batch number: t S200828; storage conditions are as follows: shielded from light and stored at 4 ℃.
(Note: lithium carbonate sustained-release tablet, which is a representative drug (belonging to lithium salt) of a mood stabilizer drug for the treatment of bipolar disorder.) the experimental purpose of the lithium carbonate sustained-release tablet in this example was as a therapeutic gold standard and in combination with a Daying tablet to compare the difference in therapeutic effects.
The experimental animals referred to in the following examples were of the species: c57 male mice, grade: SPF grade, animal number and sex: male mice 73, body weight: purchase 20g of body weight. Feeding management: the environment is adapted to 7 days before the test; feeding places: no. 1111 of the northern Shanxi in Shanghai city, no. 6 building, laboratory animal use license: SYXK (Shanghai) 2014-0018; feeding conditions are as follows: feeding density: 1/cage, cage spatial displacement frequency: 1 time/week; feeding environment conditions according to the feeding environment condition standard: national standard GB14925-2010 of the people's republic of China; raising environment control system: automatically controlling the feed of a full fresh air central air conditioning system; animals were fed with standard SPF-grade complete rat feed purchased from shanghai zhou corn poppy biotechnology limited, feed production license: shanghai feeding certificate (2021) 04027, general nutritional ingredient indexes: crude protein, crude fat, crude fiber, crude ash, moisture, calcium, and phosphorus; the feeding method comprises the following steps: free uptake; the drinking water types are as follows: experimental animal drinking water (tap water autoclaving), water supply method: the drinking bottle is used for containing and freely taking.
The analysis software referred to in the following examples is nodus (Noldus) animal behavior analysis software; statistical data are subjected to statistical treatment by SPSS software, significance detection is carried out by a one-factor variance analysis method, and difference is significant when P < 0.05.
Example 1
Animals are adaptively raised for one week, and the molding is started when the weight reaches about 20g.
The animals were randomly grouped according to body weight, 10 animals were taken as blank control group, and the remaining animals were randomly grouped (not specifically grouped) according to the weight average principle, collectively referred to as experimental mice.
Feeding the blank mice in a cage, putting the experimental mice into a specially-made 50ml centrifuge tube every morning, reserving air holes to prevent the experimental mice from freely moving or turning around, putting the experimental mice on a test tube rack, keeping the body level, and maintaining for 4 hours.
From day 14 after leasing, model group mice and blank mice were tested for sugar water preference, and all animals were given 1% sucrose water for 24h before the test began: 1% of cane sugar water is contained in the two bottles, and the two bottles are placed at the left corner and the right corner of the cage; in the next 24h, 1% sucrose water and plain drinking water were given simultaneously: 1 percent of cane sugar water is filled in one bottle, and common drinking water is filled in the other bottle and is still placed at the left corner and the right corner of the cage; then fasting and water deprivation are carried out for 23h; subsequently, a sugar water preference test was performed: 1% of sucrose and plain drinking water were given simultaneously and the amount of sucrose and plain drinking water consumed by the animals within 1h was measured by weighing the drinking bottles.
As shown in fig. 1, the percentage of sugar water preference of model group mice decreased 14 days after restraint, with a significant difference compared to the blank group (P < 0.05). The sugar water preference test is used to demonstrate the success of the experimental manufacturing model.
Example 2
To ensure that there was no difference in basal levels of each group of mice, the experimental mice were equally divided into 8 groups of 8 animals each, plus the original blank group of animals, for a total of 9 groups, according to the data of the sugar water preference experiment in example 1. During the administration period, each group corresponded to a different treatment regimen, as follows:
| group of | Molding die | Treatment of |
| Blank space | Group culture | Pure water |
| Model (model) | Isolated culture plus restraint | Pure water |
| Citalopram 2mg/kg | Isolated culture plus restraint | 2mg/kg citalopram |
| Nutrient-retaining tablet 4g/kg | Isolated culture plus restraint | 4g/kg nutrientSheet |
| Camping tablet 2g/kg | Isolated culture plus restraint | 2g/kg nutrient-retaining tablet |
| 1g/kg of nutrition-regulating tablet | Isolated culture plus restraint | 1g/kg nutrient-retaining tablet |
| Citalopram 2mg/kg + danying tablet 1g/kg | Isolated culture plus restraint | 2mg/kg citalopram +1g/kg camping tablet |
| Lithium carbonate 0.24g/kg | Isolated culture plus restraint | 0.24g/kg lithium carbonate |
| 0.24g/kg of lithium carbonate and 1g/kg of nutrition-activating tablet | Isolated culture + restraint | 0.24g/kg lithium carbonate +1g/kg nutrition tablet |
On the basis of example 1, experimental mice were kept in single-cage rearing and daily restrained, given the corresponding medication for 21 consecutive days, 1 hour after the last administration, and subjected to sugar water preference, open field test and elevated plus maze test, one item per day. The experimental mice were restrained for a total of 35 days (including the dosing period).
(1) Sweet water preference level
After 3 weeks of administration, the sugar water preference test was performed on the blank mice and the experimental mice, and the specific results are shown in fig. 2.
As can be seen from fig. 2, the sugar water preference ratio of the model group mice was lower than that of the blank control group, with a statistically significant difference (P < 0.01);
citalopram at 2mg/kg increased the sugar water preference ratio of the mice, which was very significantly different from the model group (P < 0.01);
the 2mg/kg citalopram +1g/kg nutrition tablet can also increase the sugar water preference ratio of the mice, and has a significant difference compared with a model group (P < 0.05);
1g/kg of the nutrition tablet alone can improve the sugar water preference ratio of the mice, and has very significant difference compared with a model group (P < 0.01);
2g/kg of the Danying tablet alone can improve the sugar water preference ratio of the mice, and the sugar water preference ratio is not different from that of a model group (P is more than 0.05);
the sugar water preference ratio of the mice cannot be improved by using the camping tablet alone at 4g/kg, and the sugar water preference ratio is not different from that of a model group (P is more than 0.05);
neither 0.24g/kg lithium carbonate nor 0.24g/kg lithium carbonate +1g/kg daikon tablets appeared to have an improving effect on the sugar water preference of mice.
(2) Elevated cross maze experiment
After 3 weeks of administration, the air-white mice and experimental mice were subjected to an elevated plus maze assay, and the results are shown in fig. 3.
As can be seen from fig. 3, the arm-closing time of the model group mice was higher than that of the blank control group, with a statistically significant difference (P < 0.01);
citalopram at 2mg/kg reduced the arm-closing time of the mice with a significant difference compared to the model group (P < 0.05);
the 2mg/kg citalopram +1g/kg camping tablet can also reduce the arm closing time of the mice, and has a significant difference compared with a model group (P < 0.05);
the arm closing time of the mouse can be shortened by using 4g/kg of the camping tablet alone, and the difference is significant compared with a model group (P < 0.05);
the arm-closing time of mice using 2g/kg and 1g/kg of the camping tablet alone is not different from that of the model group (P > 0.05);
0.24g/kg of lithium carbonate did not improve the arm-closing time of the mice, and was not different from the model group (P > 0.05);
0.24g/kg lithium carbonate +1g/kg nutrition tablet can reduce the arm closing time of the mice, and has a significant difference compared with the model group (P < 0.05).
(3) Experiment of autonomic activity
The results of autonomic activity measurements on the blank mice and experimental mice 3 weeks after administration are shown in fig. 4.
As can be seen from fig. 4, the number of autonomic activities of the model group mice was lower than that of the blank control group, but there was no statistically significant difference;
citalopram at 2mg/kg increased the number of voluntary movements of the mice;
the number of autonomous activities of the mice is also increased by 2mg/kg of citalopram and 1g/kg of camping tablets;
1g/kg of the camping tablet is used independently, so that the number of autonomous activities of the mouse is increased;
the times of the autonomic activities of the mice using 2g/kg and 4g/kg of the camping tablets alone are not different from those of the model group;
the 0.24g/kg lithium carbonate increases the number of autonomous activities of the mice;
the number of autonomous activities of the mouse is increased by 0.24g/kg of lithium carbonate and 1g/kg of nutrition tablets;
there were no statistical differences between the groups compared to the model group.
Therefore, from the experimental results, when the sugar water preference determination is carried out 14 days after the mice are restrained, the percentage of the sugar water preference of the model group mice is reduced, which indicates that the mice have depressive behaviors, the sugar water preference ratio of the mice is increased by both the citalopram and the low-dose camping tablet, and the sugar water preference ratio of the mice can also be increased by 2mg/kg of citalopram and 1g/kg of camping tablet, which indicates that the citalopram and the camping tablet have antidepressant effects on the model mice;
1g/kg of the Danying tablets can be used independently to improve the sugar water preference ratio of the mice;
in the elevated plus maze, it can be seen that the high dose of the Dan pian, the citalopram, and the combination of the Dan pian and the citalopram can improve the anxiety level of the mice, and the combination of the Dan pian and the lithium carbonate can also improve the anxiety level of the mice, which indicates that the Dan pian has the function of antianxiety, and the arm closing time of the Dan Ying pian and the citalopram is shorter than that of the citalopram alone, thus suggesting that the Dan Ying pian may have the efficacy of strengthening antianxiety drugs;
in the autonomic activity experiments, the results showed that the level of autonomic activity was different for each group of mice, but there was no statistical difference (P > 0.05) between the control model groups, indicating that the motility of the mice per group was not different per se, thus ensuring the quality control of the study. Meanwhile, the autonomous activities of the mice in the citalopram group and the lithium carbonate group are improved, although the autonomous activities are not different from those of the model group, the antidepressant drug mice always show a state of increased autonomous activities in multiple experiments in the laboratory, the autonomous activities of the dacron and the citalopram when used together are reduced compared with the autonomous activities of the citalopram when used alone, and the autonomous activities of the dacron and the lithium carbonate when used together are reduced compared with the autonomous activities of the lithium carbonate when used alone, so that the trend that the autonomous activities of bipolar affective disorder animals caused by antidepressant drugs are increased is suggested to be reduced for the dacron.
In the embodiment, the sugar water preference degree of the mouse is reduced through a mouse model causing anxiety and depression co-morbidity by a chronic constraint stress model, so that the arm closing time of the elevated plus maze of the mouse is prolonged. The curative effect of the danying tablets on treating the bipolar disorder model mouse by combining with antidepressant drugs and anti-bipolar disorder drugs is observed, and a treatment basis is provided for patients suffering from bipolar disorder, depression and anxiety.
In this specification, the invention has been described with reference to specific embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.
Claims (6)
1. Application of the nutrition-activating tablet in preparing medicines for treating anxiety and depression co-diseases, depression or anxiety neurosis.
2. The use according to claim 1, wherein the anxio-depressive co-disease is bipolar disorder.
3. The use according to claim 1 or 2, characterized in that the dose of the tablet is varied to prepare a medicament for treating anxiety symptoms in a co-morbid anxiety and depression or for treating depression symptoms in a co-morbid anxiety and depression.
4. The use according to claim 3, wherein the dosage of the nutrition tablet for the preparation of a medicament for the treatment of anxiety symptoms in anxiety-depression co-morbidities is greater than the dosage of the nutrition tablet for the preparation of a medicament for the treatment of depression symptoms in anxiety-depression co-morbidities.
5. Use according to claim 1 or 2, characterized in that anxiety symptoms and depressive symptoms in depression, anxiety or a co-morbid anxiety and depression are treated by a combination of a camping tablet and citalopram.
6. Use according to claim 1 or 2, characterized in that the anxiety symptoms in anxiety disorders or co-morbidities with anxiolytic depression are prepared by a combination of a nutrition tablet and lithium carbonate.
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| CN102008688A (en) * | 2010-12-09 | 2011-04-13 | 上海市精神卫生中心 | Medicament for treating periodic psychosis |
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