Anti-depression oral liquid containing medicinal and edible components as well as preparation method and application of anti-depression oral liquid

Abstract

The invention discloses an anti-depression oral liquid containing medicinal and edible components and a preparation method and application thereof, the oral liquid is mainly composed of soy isoflavone, ginsenoside, lily, jasmine flower, centella asiatica and ginkgo leaf, and the oral liquid is prepared by extracting and compounding according to a specific proportion. The stable and safe functional beverage is obtained through modern process extraction, alcohol precipitation and concentration treatment; animal experiments show that the oral liquid can significantly improve sweet water preference, reduce behavioral despair and regulate neurotransmitter and endocrine indexes such as 5-HT, ACTH and CORT, and has a good anti-depression effect; the traditional Chinese medicine composition is natural in formula, low in toxic and side effects, clear in preparation process, suitable for being developed into antidepressant drugs or functional food and wide in application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of food and health care products, and relates to an antidepressant oral liquid prepared by utilizing medicinal and edible homologous ingredients, a preparation method thereof, and application thereof in the intervention of depression. Background Art

[0002] Currently, the most widely used antidepressants in clinical practice include selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). These drugs have some efficacy in increasing levels of neurotransmitters such as serotonin (5-HT), norepinephrine, and cortisol (CORT). However, they are associated with significant side effects, including but not limited to sexual dysfunction, weight gain, drowsiness, insomnia, gastrointestinal discomfort, and the development of drug resistance. Long-term use may also lead to dependence or drug withdrawal syndrome. Furthermore, these drugs take a long time to work, with some patients experiencing no significant relief even after eight weeks.

[0003] Therefore, developing a new antidepressant with mild effects, high safety, suitable for long-term use, and proven efficacy has become an important direction in current drug research and development. In recent years, medicinal and edible plants have gradually become a research hotspot for the adjunctive treatment of mental illness due to their advantages of being natural, having minimal toxic side effects, and regulating multiple metabolic pathways.

[0004] In order to solve the above technical problems, the present invention combines modern pharmacological research with the theoretical basis of traditional Chinese medicine such as "seven emotions causing illness" and "emotional internal injury", and rationally screens medicinal and edible plants with the effects of calming the mind, nourishing the heart, soothing the liver, and clearing the brain, including medicinal and edible ingredients of soy isoflavones, ginsenosides, lily, jasmine, ginkgo leaves and Centella asiatica, and compounding them into an oral liquid dosage form to provide a plant formula preparation with multi-target and multi-mechanism synergistic antidepressant effects. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the present invention provides an antidepressant oral liquid containing medicinal and edible ingredients, and a preparation method and application thereof.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] An antidepressant oral solution containing medicinal and edible ingredients selected from: lily, soy isoflavones, ginsenosides, jasmine, centella asiatica, and ginkgo leaves;

[0008] By weight, the ratio of m lily: m soy isoflavones: m ginsenosides: m jasmine: m centella asiatica: m ginkgo leaves is 1:3:2:2:1:1.

[0009] The present invention also provides a method for preparing the antidepressant oral liquid containing the medicinal and edible ingredients, comprising the following steps:

[0010] 1) Add lily bulbs, soy isoflavones, ginsenosides, jasmine flowers, Centella asiatica, and ginkgo leaves in 18,000 liters of water according to weight ratio and soak for 30 minutes;

[0011] 2) First decoction for 1-2 hours, filter to obtain the primary filtrate;

[0012] 3) After filtering, add water to the remaining medicinal residue and boil it for another 1-2 hours, filter it, and combine the obtained filtrate with the initial filtrate;

[0013] 4) Concentrating the combined filtrate from step 3) and subjecting it to two rounds of alcohol precipitation, stirring for 20-40 minutes each time, allowing it to stand for 10-14 hours, and filtering to remove the residue;

[0014] 5) After distillation, separation and recovery of ethanol, the antidepressant oral liquid containing the medicinal and edible ingredients is obtained.

[0015] Preferably, the alcohol precipitation treatment in step 4) is stopped when the ethanol concentration reaches 75-80%.

[0016] The present invention also discloses an antidepressant oral liquid containing medicinal and edible ingredients, and use of the antidepressant oral liquid in the preparation of antidepressant drugs or functional foods.

[0017] Preferably, the antidepressant oral solution containing the medicinal and edible ingredients exerts an antidepressant effect by regulating the levels of 5-HT, ACTH and CORT through the medicinal and edible ingredients.

[0018] Beneficial effects of the present invention:

[0019] 1) Green and natural, with minimal toxicity and side effects: The formula is composed entirely of medicinal and edible ingredients, with no chemically synthesized ingredients, and there is no risk of addiction with long-term use;

[0020] 2) Through biochemical pathways (5-HT, ACTH, CORT), it has a multi-mechanism combined drug effect;

[0021] 3) Scientific synergistic ratio: Soy isoflavones and ginsenosides work together as the main ingredients, supplemented by lily, centella asiatica, jasmine, and ginkgo biloba, embodying the concept of "monarch, minister, assistant, and envoy" in compound Chinese medicine;

[0022] 4) The preparation process is clear and controllable: The extraction, alcohol precipitation, and concentration processes have clear standards and do not involve the extraction or addition of hazardous substances, which is a green production method;

[0023] 5) Possesses industrialization prospects: Experimental data show that the oral liquid can replace some clinical antidepressants and be put on the market as a functional beverage, health food or auxiliary medicine.

[0024] In summary, the present invention provides an oral liquid preparation with a synergistic antidepressant effect. The preparation is prepared with soy isoflavones and ginsenosides as main ingredients, supplemented with medicinal and edible plants such as lily, Centella asiatica, jasmine, and ginkgo biloba, through scientific proportioning and extraction methods. The present invention also discloses the preparation process of the oral liquid and its specific application in alleviating depressive symptoms. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 is the sugar water preference index of each group (%); Figure 2 is the immobility time in the tail suspension test (seconds); Figure 3 is the forced swimming immobility time (seconds); Figure 4 is the change graph of serum 5-HT content (ng / mL); Figure 5 is the change graph of serum ACTH content (pg / mL); Figure 6 Figure 2 is a graph showing changes in serum CORT levels (ng / mL). DETAILED DESCRIPTION

[0026] The present invention is further described below by specific examples. In order to make the invention purpose, technical solution and beneficial technical effect of the present invention clearer, the present invention is further described in detail below with reference to the examples. It should be understood that the embodiments described in this specification are only for explaining the present invention and are not intended to limit the present invention.

[0027] Unless otherwise stated, all films and reagents used in the examples are commercially available or synthesized according to conventional methods and can be used directly without further treatment. The instruments used in the examples are also commercially available.

[0028] Animal Experimental Design: 72 SPF male Sprague-Dawley rats were established with a CUMS depression model and divided into six groups: a blank group, a model group, a fluoxetine group (10 mg / kg), and low-, medium-, and high-dose oral liquid groups. After 21 days of continuous gavage, behavioral and biochemical changes were assessed. This study aimed to validate the antidepressant efficacy of a novel oral liquid containing rhamnoides and ginsenosides as primary ingredients, supplemented with medicinal and edible plants such as lily, Centella asiatica, jasmine, and ginkgo biloba, in a rat model of chronic stress depression and to explore its mechanism of action.

[0029] Experimental Materials:

[0030] Animals: SPF male SD rats (weighing 200-250 g) were randomly divided into 6 groups, with 12 rats in each group.

[0031] Oral solution: the antidepressant oral solution of the present invention.

[0032] Control group: normal saline control group, fluoxetine (10 mg / kg) positive control group.

[0033] Experimental methods:

[0034] A. Establishment of animal model: The chronic unpredictable mild stress (CUMS) method model was used. The stimulation projects included ice water swimming, solitary cage breeding, day and night reversal, etc., which lasted for 28 days to establish a rat depression model.

[0035] B. Administration method: The experimental group rats were given the drug by oral gavage every day for 21 days; the control group and the positive control group were given the corresponding normal saline and fluoxetine, respectively.

[0036] C. Behavioral Assessment:

[0037] Sugar water preference experiment: Measure the rats' preference for 1% sucrose water, reflecting their anhedonia symptoms.

[0038] Tail suspension test: The time rats remain motionless when suspended upside down is measured to assess changes in their depressive behavior.

[0039] Forced swim test: measures the time rats can remain motionless in water to assess their stress response.

[0040] D. Biochemical index detection:

[0041] 5-HT (serum serotonin): The 5-HT level in depressed rats was significantly decreased, and the 5-HT concentration in serum was detected by ELISA.

[0042] ACTH and CORT (serum cortisol and adrenocorticotropic hormone): measure changes in their levels to assess stress response and relief of depressive symptoms.

[0043] Example 1:

[0044] Use 225 grams of lilies, 675 grams of soy isoflavones, 450 grams of ginsenosides, 450 grams of jasmine flowers, 225 grams of centella asiatica, and 225 grams of ginkgo leaves, add 18,000 liters of water, warm soak for 30 minutes, and extract. Decoct for 1.5 hours and filter into medicinal residues and filtrate. The medicinal residues are repeatedly filtered, decoct for 1.5 hours and add 18,000 liters of water, and discard unnecessary medicinal residues. The filtrate filtered again and the original filtrate are merged. And concentrate and carry out alcohol precipitation, make alcohol content to more than 75%, stir and leave standstill 12 hours after 30 minutes. Filter, obtain residue and filtrate, then add the ethanol solution of the same amount, 75% ethanol, leave standstill 12 hours again, filter and discard the medicinal residues again, with the filtrate filtered last time and this time merge ethanol liquid, reclaim ethanol and obtain oral liquid.

[0045] Under the basic formula (1:3:2:2:1:1), we increased or decreased the dosage of ginsenosides and soy isoflavones, setting them as follows:

[0046] Low-dose group: soy isoflavones 30 mg / kg, ginsenosides 20 mg / kg;

[0047] Medium-dose group: 60 mg / kg, 40 mg / kg;

[0048] High-dose group: 90 mg / kg, 60 mg / kg;

[0049] Verify the antidepressant effect of oral solution with different dosage ratios on CUMS rats;

[0050] Example 2:

[0051] A traditional Chinese medicine for tranquilizing the nerves (concentrated Suanzaoren Decoction, 10 mL / kg) was used for comparison with a high-dose group treated with the present invention. After 21 days of intervention, the present invention group showed a 66.4% improvement in sugar preference compared with a 41.7% improvement in the Suanzaoren Decoction group. Furthermore, the present invention group showed a 3.8 ng / mL increase in 5-HT compared with a 2.2 ng / mL increase in the Suanzaoren Decoction group.

[0052] Example 3:

[0053] SD rats were given 3 times the clinically recommended dose by gavage for 28 consecutive days, and their body weight, food intake, liver and kidney function indicators, blood routine and other biochemical parameters were observed. No obvious abnormal changes were found, indicating that the preparation is safe for long-term use and has the potential for development as a health product.

[0054] Experimental data:

[0055] Group Sugar water preference (%) Tail suspension time (seconds) Forced swimming immobility time (seconds) 5-HT (ng / mL) ACTH (pg / mL) CORT (ng / mL) Blank group 80.5 30.3 60.5 8.12 40.2 45.3 control group 45.3 120.4 150.8 3.11 120.4 150.8 Positive control group 70.2 60.1 75.2 6.8 60.1 70.2 Low-dose group 57.6 85.4 100.1 5.32 80.6 95.3 Medium dose group 63.1 70.5 85.3 5.76 65.7 80.5 High-dose group 75.4 52.2 65.2 6.9 60.1 72

[0056] Data and analysis:

[0057] ⅰ Sugar water preference test: The sugar water preference index of the model group rats was significantly lower than that of the blank group (P<0.01), indicating that the model rats showed typical "anhedonia" behavior. The low-dose group of the new oral liquid showed a more significant improvement (P<0.05), while the effect of the high-dose group was similar to that of the fluoxetine group (P<0.01). See Appendix Figure 1 .

[0058] ⅱ Tail suspension test: The immobility time of the model group was significantly longer than that of the blank group (P<0.01), indicating that the depressive symptoms were more severe. All experimental groups showed a significant reduction in immobility time compared with the model group, especially the high-dose group and the fluoxetine group, with significant differences (P<0.05). See Appendix Figure 2 .

[0059] ⅲ Forced swimming test: The immobility time of the model group rats was significantly higher than that of the blank group (P<0.01). The effects of the medium and high dose groups of the new oral solution were similar to those of the fluoxetine group (P<0.05), showing a significant antidepressant effect. Figure 3 .

[0060] ⅳBiochemical indicators: 5-HT in serum of rats in the model group (see Figure 4 ), ACTH and CORT levels (see Figure 5 and 6 The new oral liquid treatment group showed a significant recovery of 5-HT levels and a decrease in ACTH and CORT levels, especially in the high-dose group, which had the most similar effects to the fluoxetine group.

[0061] Summary: The behavioral scores (tail suspension immobility time and forced swimming immobility time) of the medium and high-dose groups were significantly improved, better than those of the low-dose group and comparable to those of the fluoxetine group (P<0.01). The behavioral indicators and serum indicators supported each other, indicating that this preparation exerts antidepressant effects at both the neural and endocrine levels. Compared with traditional Chinese medicines, the present invention is more effective in regulating anhedonia and neurotransmitters. The oral solution is highly safe.

[0062] In summary, the antidepressant oral liquid containing medicinal and edible ingredients provided by the present invention has a significant antidepressant effect, showing relatively ideal improvements in multiple behavioral and biochemical indicators, especially showing strong therapeutic potential in regulating neurotransmitters and endocrine stress responses. The effective ingredients and dosage combination of this oral liquid preparation have good antidepressant effects and are worthy of further development and application.

Claims

1. An antidepressant oral solution containing medicinal and edible ingredients, characterized in that: The medicinal and edible ingredients include soy isoflavones, ginsenosides and plant extracts derived from lily, jasmine, centella asiatica and ginkgo leaves; By weight, the ratio of m lily: m soy isoflavones: m ginsenosides: m jasmine: m centella asiatica: m ginkgo leaves is 1:3:2:2:1:

1.

2. The method for preparing the antidepressant oral liquid containing the medicinal and edible ingredients according to claim 1, characterized in that: The steps include: 1) Add lily bulbs, soy isoflavones, ginsenosides, jasmine flowers, Centella asiatica, and ginkgo leaves in 18,000 liters of water according to weight ratio and soak for 30 minutes; 2) First decoction for 1-2 hours, filter to obtain the primary filtrate; 3) After filtering, add water to the remaining medicinal residue and boil it for another 1-2 hours, filter it, and combine the obtained filtrate with the initial filtrate; 4) Concentrating the combined filtrate from step 3) and subjecting it to two rounds of alcohol precipitation, stirring for 20-40 minutes each time, allowing it to stand for 10-14 hours, and filtering to remove the residue; 5) After distillation, separation and recovery of ethanol, the antidepressant oral liquid containing the medicinal and edible ingredients is obtained.

3. The preparation method according to claim 2, wherein the alcohol precipitation treatment in step 4) is stopped when the ethanol concentration reaches 75-80%.

4. Use of antidepressant oral liquid containing medicinal and edible ingredients in the preparation of antidepressant drugs or functional foods.

5. The use according to claim 4, characterized in that Antidepressant oral solution containing medicinal and edible ingredients exerts antidepressant effects by regulating the levels of 5-HT, ACTH and CORT through medicinal and edible ingredients.

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