Method for improving or regulating emotions and composition

Abstract

A method for improving or regulating subjects' emotions, comprising: administering to subjects a composition comprising an effective amount of anandamide or a derivative thereof before, during, or after exercises or physical activities. Also disclosed is a composition comprising anandamide or a derivative thereof, which can be administered before, during, or after exercises or physical activities, to improve or regulate mammals' emotions. The described method and composition can alleviate anxiety, stress, depression, obsessive compulsive disorder, or bipolar disorder.

Description

Methods and compositions for improving or regulating mood Technical Field

[0001] This invention belongs to the field of biotechnology, specifically relating to a method for improving or regulating the emotions of a subject. Background Technology

[0002] Regular physical exercise is considered an important factor in improving mood. Exercise can stimulate the release of neurotransmitters, including endorphins and dopamine, both of which are closely related to feelings of pleasure and well-being. Arachidonic acid ethanolamine (AEA), also known as eicosapentaenoic acid ethanolamine, is an endocannabinoid neurotransmitter. The endocannabinoid system is an important lipid signaling system that existed before vertebrate evolution and is well preserved across species. In mammals, it has recently been identified as a regulator of a variety of physiological processes, including inflammation and pain, appetite, mood, and prenatal and postnatal development. Furthermore, the endocannabinoid system is an important component of neuronal substrates involved in brain reinforcement and reward processes.

[0003] This invention discovers that arachidonic acid ethanolamine can be combined with exercise to effectively improve mood and reduce anxiety and depressive symptoms by regulating the endocannabinoid system and promoting neurotransmitter release. Technical issues

[0004] On one hand, the present invention provides a method for improving or regulating the mood of a subject, the method comprising: administering to the subject a composition containing an effective amount of arachidonic acid ethanolamine or a derivative thereof before, during, or after exercise or training.

[0005] In some implementations, the emotion includes anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

[0006] In some embodiments, the composition is administered by a single dose or multiple fractions, with an dosage range of 50 mg to 2500 mg. In some embodiments, the dosage range is 50 mg to 2000 mg, 100 mg to 1500 mg, 100 mg to 1200 mg, 100 mg to 1000 mg, 100 mg to 1000 mg, 100 mg to 800 mg, 150 mg to 800 mg, 200 mg to 600 mg, 250 mg to 600 mg, 200 mg to 500 mg, or 260 mg to 500 mg.

[0007] In some embodiments, the composition may be applied once daily or every other day for a period of time, such as 3 days to 1 week, 4 days to 1 week, 4 days to 4 weeks, 4 days to 7 weeks, 4 days to 14 weeks, 1 week to 7 weeks, 2 weeks to 7 weeks, 3 weeks to 7 weeks, 4 weeks to 7 weeks, 1 week to 14 weeks, 2 weeks to 14 weeks, 3 weeks to 14 weeks, or 4 weeks to 14 weeks. For example, it may be taken before, during, and / or after exercise for a period of time, as described above.

[0008] In some implementations, arachidonic acid ethanolamine or its derivatives are prepared as solid or liquid formulations.

[0009] In some implementations, arachidonic acid ethanolamine or its derivatives are in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, and syrups.

[0010] In some implementations, the subjects are mammals. In some implementations, the subjects are humans.

[0011] In some implementations, arachidonic acid ethanolamine or its derivatives are formulated into nutritional products, dietary supplements, foods, beverages, or animal feed.

[0012] In some implementations, administration is carried out via a route selected from: oral, intravenous, intramuscular, intraperitoneal, or sublingual administration.

[0013] In one aspect, the present invention provides a composition comprising arachidonic acid ethanolamine or a derivative thereof, which is administered to a subject before, during, or after exercise to improve or regulate the subject's mood.

[0014] In some implementations, the emotion includes anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

[0015] In some embodiments, the dosage of the composition is 50 mg to 2500 mg.

[0016] In some embodiments, the composition can be administered via various routes, including oral, intravenous, intramuscular, intraperitoneal, local infusion, or sublingual administration. For example, the composition can be administered as a single dose or in multiple divided doses, with daily dose ranges of 50 mg to 2000 mg, 100 mg to 1500 mg, 100 mg to 1200 mg, 100 mg to 1000 mg, 100 mg to 1000 mg, 100 mg to 800 mg, 150 mg to 800 mg, 200 mg to 600 mg, 250 mg to 600 mg, 200 mg to 500 mg, and 260 mg to 500 mg.

[0017] In some embodiments, the composition is prepared as a solid or liquid formulation.

[0018] In some embodiments, the composition is formulated as a nutritional product, dietary supplement, food, beverage, or animal feed.

[0019] In some embodiments, the composition is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, or syrups.

[0020] In another aspect, the present invention provides the use of arachidonic acid ethanolamine or a derivative thereof in the preparation of a composition for improving or regulating the mood of a subject, wherein the composition comprises an effective amount of arachidonic acid ethanolamine or a derivative thereof is administered before, during, or after exercise or physical activity.

[0021] In some implementations, the emotion includes anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

[0022] In some embodiments, the composition is used to prepare nutritional products, dietary supplements, health products, foods, beverages, and animal feed, wherein the weight ratio of the composition of the present invention in the nutritional products, dietary supplements, foods, beverages, and animal feed is 0.1-95%.

[0023] In some embodiments, the composition of the present invention is 10-60% by weight in nutritional products, dietary supplements, foods, beverages, and animal feed.

[0024] In some embodiments, the composition may be applied once daily or every other day for a period of time, such as 3 days to 1 week, 4 days to 1 week, 4 days to 4 weeks, 4 days to 7 weeks, 4 days to 14 weeks, 1 week to 7 weeks, 2 weeks to 7 weeks, 3 weeks to 7 weeks, 4 weeks to 7 weeks, 1 week to 14 weeks, 2 weeks to 14 weeks, 3 weeks to 14 weeks, or 4 weeks to 14 weeks. For example, it may be taken before, during, and / or after exercise for a period of time, as described above.

[0025] In some embodiments, the composition can be administered via various routes, including oral, intravenous, intramuscular, intraperitoneal, local infusion, or sublingual administration. In some embodiments, the dosage of the composition ranges from 50 mg to 2500 mg. Specifically, the daily dosage range of the composition is 50 mg to 2000 mg, 100 mg to 1500 mg, 100 mg to 1200 mg, 100 mg to 1000 mg, 100 mg to 1000 mg, 100 mg to 800 mg, 150 mg to 800 mg, 200 mg to 600 mg, 250 mg to 600 mg, 200 mg to 500 mg, and 260 mg to 500 mg.

[0026] In some embodiments, the composition is prepared as a solid or liquid formulation.

[0027] In some embodiments, the composition is formulated as a nutritional product, dietary supplement, food, beverage, or animal feed.

[0028] In some embodiments, the composition is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, or syrups.

[0029] This invention involves administering arachidonic acid ethanolamine or a derivative thereof to a subject (human or mammal) for a predetermined period (e.g., at least 3-14 days) before, during, or after exercise or training to regulate or improve the subject's mood, including anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder. This invention can be administered in various forms, such as aqueous solutions, aqueous suspensions, capsules, drops, granules, liquids, powders, syrups, tablets, functional foods, beverages, toothpaste, or sublingual preparations (e.g., orally or by injection). It can be administered by a single dose or multiple doses. Attached Figure Description

[0030] Figure 1 shows the immobility time of the three groups of mice during the forced swimming test (FST). Detailed Implementation

[0031] The present invention will now be further described with reference to preferred embodiments thereof. While the invention will be described in conjunction with preferred embodiments, it should be understood that they are not intended to limit the invention to these embodiments. Rather, the invention is intended to cover alternatives, modifications, and equivalents that may be included within the spirit and scope of the invention as defined in the claims. Furthermore, numerous specific details are set forth in the detailed description of the invention to provide a thorough understanding of the invention. However, it will be apparent to those skilled in the art that the invention may be practiced without these specific details. In other instances, well-known methods, procedures, components, and other features have not been described in detail so as not to unnecessarily obscure aspects of the invention.

[0032] As used herein, the term “or” is intended to include both “and” and “or”. In other words, the term “or” can also be replaced with “and / or”.

[0033] As used herein, unless the context clearly indicates otherwise, the singular forms “a / an” and “the” are intended to include the plural forms as well.

[0034] As used herein, the terms “comprising” or “including” or variations thereof refer to items that are included in the context of the term in their non-restrictive sense, but do not exclude items not specifically mentioned. It also includes the more restrictive verbs 'consistently composed of' and 'comprises of'.

[0035] As used herein, the terms “subject” and “individual” are used interchangeably to refer to any subject to whom the methods and compositions of this disclosure may be applied or administered. A subject may have a disease or ailment, but does not need to be ill to benefit from the methods and compositions of this disclosure. Any subject may take the disclosed compositions or become a recipient of the disclosed methods. In this document, the term “subject” refers to an animal (e.g., birds, reptiles, and mammals). In some embodiments, the subject may be a mammal including non-primates (e.g., camels, donkeys, zebras, cows, horses, cats, dogs, rats, and mice) and primates (e.g., monkeys, chimpanzees, and humans). In some embodiments, the subject may be a non-human mammal. In other embodiments, the subject may be a human.

[0036] Stress, anxiety, depression, obsessive-compulsive disorder (OCD), and bipolar disorder are common mental health problems in modern society, each with unique manifestations and impacts. Stress refers to a psychological and physiological response experienced by an individual when facing external or internal challenges, threats, or demands. Anxiety disorder is a mental disorder diagnosed when an individual's anxiety level and duration exceed normal limits and severely impact daily life. Depression is a common mental health problem characterized by persistent sadness, loss of interest or pleasure, and decreased energy. Obsessive-compulsive disorder (OCD) is characterized by uncontrollable, recurring unpleasant or disturbing thoughts, impulses, or images—obsessive thoughts—and compulsive behaviors performed to alleviate anxiety caused by these obsessive thoughts. Bipolar disorder is a mood disorder characterized by extreme fluctuations in mood between mania (high depression) and hyperactivity (low depression).

[0037] As used in this invention, the term "administration" refers to the direct administration of a compound or a pharmaceutically acceptable salt or composition thereof to a subject, or the administration of a prodrug derivative or analog thereof of a compound or a pharmaceutically acceptable salt or composition thereof to a subject, which may form an equivalent amount of the active compound in the subject's body.

[0038] The compositions of the present invention containing arachidonic acid ethanolamine or its derivatives can be used with dietaryly or pharmaceutically acceptable carriers. These carriers include non-toxic, compatible substances commonly used in health foods, dietary supplements, and pharmaceutical preparations, such as sugars, starches, cellulose and their derivatives, powdered tragacanth gum, malt, gelatin, talc, oils, glycols, polyols, esters, agar, alginic acid, pyrogen-free water, isotonic saline, etc.

[0039] The compositions of the present invention can be administered together with other supplements, such as vitamins, minerals, nootropics, and other supplements known in the art.

[0040] The compositions of the present invention and various formulations thereof are considered; the compositions will be formulated as nutritional supplements or dietary supplements, (medical) foods, beverages, animal feeds, in liquid or solid form. For oral administration, the compositions of the present invention may be in any suitable form, including solutions, tablets, gel capsules, capsules, or alternative nutritional foods or supplements.

[0041] The intended method involves administering an appropriate amount of the substance or composition daily, depending on the specific formulation and form of the substance and composition. This daily amount can be administered once or multiple times. Typically, an effective amount administered once or multiple times daily is 100 mg to 1000 mg. One or more doses can be administered once daily at any time. For example, an effective dose can be administered daily for one day, several days, multiple days, or indefinitely, and the composition can be administered for 7 days or more within a cycle, depending on the desired effect. More typically, daily doses are 50 mg to 2000 mg, 100 mg to 1500 mg, 100 mg to 1200 mg, 100 mg to 1000 mg, 100 mg to 1000 mg, 100 mg to 800 mg, 150 mg to 800 mg, 200 mg to 600 mg, 250 mg to 600 mg, 200 mg to 500 mg, and 260 mg to 500 mg. More typically, the daily dosage is 200 mg to 600 mg.

[0042] The technical features, implementation methods, and beneficial effects of the present invention will be further described in detail below with reference to specific implementation examples. The embodiments described below are only some embodiments of the present invention, and not all embodiments. Unless otherwise specified, the materials and reagents described in the following embodiments are all commercially available products that can be purchased from the market. Example

[0043] Animal model construction

[0044] Twenty male C57BL / 6J mice (18–22 g, approximately 8–10 weeks old) were housed in a cage with a normal photoperiod, with lights on for 12 hours and off for 12 hours (lights on from 8:00 AM to 8:00 PM). The temperature was maintained at 22 ± 2 °C, and the relative humidity was kept at 45–65%. All mice had free access to food and water. Mice were allowed one week to acclimatize before being used in any experiments.

[0045] A mouse model of depression was induced using reserpine. Specifically, reserpine was dissolved in glacial acetic acid and diluted with distilled water to a final concentration of 0.5% acetic acid. To induce depression, mice were injected with reserpine (1 mg / kg, subcutaneously daily) for 8 consecutive days.

[0046] Supplement AEA

[0047] Mice treated with reserpine were randomly divided into 4 groups of 5 mice each, including a control group and a treatment group, as follows:

[0048] Group 1 (control group): After fasting for two hours every morning, mice were given oral saline for four consecutive days. One hour after the saline was administered, reserpine was injected intraperitoneally. Then, food was provided for four consecutive days.

[0049] Group 2 (Exercise Group): After fasting for two hours each morning, mice were given oral saline solution, followed by intraperitoneal injection of reserpine one hour later, and then food was provided for four consecutive days. Each afternoon, the mice were allowed to run on a treadmill with an incline of 0 at a speed of 8 meters per minute for 30 minutes each time for four consecutive days.

[0050] Group 3 (AEA administration, dose of 52 mg / kg): After fasting for two hours each morning, mice were given oral saline containing AEA, followed by intraperitoneal injection of reserpine one hour later, and then fed for 4 consecutive days.

[0051] Group 4 (AEA + exercise, AEA dose of 52 mg / kg): After fasting for two hours every morning, mice were given saline containing AEA orally, followed by intraperitoneal injection of reserpine one hour later, and then food was provided; every afternoon, the mice were allowed to run on a treadmill with an incline of 0 at a speed of 8 m / min for 30 minutes each time, for 4 consecutive days.

[0052] The total treatment period is approximately 19 days, including a one-week adaptation period, an eight-day induction period, and a subsequent four-day supplementary period.

[0053] Depression analysis

[0054] The forced swimming test (FST) is a commonly used method in biomedical research to assess the level of depression in mice. The FST is based on the behavior of animals struggling to escape in water. When mice are placed in water, they initially exhibit vigorous swimming to try to escape, but after a period of time, they gradually give up struggling and remain motionless. This behavior is considered a state of "despair" in the animal, reflecting depressive-like behavior. Mice in each group were placed in a transparent water tank with a diameter of 25 cm, a height of 30 cm, a water depth of approximately 15 cm, and a water temperature maintained at 21-25°C. The time the mice remained motionless over 360 seconds was recorded. The longer a mouse remained floating motionless, the more severe its depression.

[0055] Statistical methods such as t-tests are typically used to compare immobility time and other behavioral indicators in different groups of mice to assess the success of establishing a depression model. These experiments can effectively screen for potential antidepressants and provide insights into the mechanisms of depression. Figure 1 shows the results of immobility time during the first stage of irritation (FST). The results show that, compared with the control group (**P < 0.01), the immobility time during FST was significantly reduced in the AEA + exercise group (34.7%); compared with the exercise group (16.6%); and compared with the AEA group (18.7%) (*P < 0.05). These statistical results indicate that the combination of AEA and exercise is significantly more effective than exercise alone or AEA alone, with a significant difference.

[0056] In the prior art (Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the antidepressant activity of amitriptyline but not desipramine, in the forced swim test in mice, J Neural Transm (Vienna). 2012 Jan 4; 119 (6): 645-652), the effects of two typical drugs, scopolamine and its combination with sildenafil, on immobility time in the forced swim test in mice were tested. The typical two-drug combination therapy in the literature achieved a 25% reduction in immobility time. The AEA+exercise technique of this invention achieved a 34.7% reduction in immobility time. This improvement was not only statistically significant compared to the control group and the univariate group, but more importantly, it significantly exceeded the effect achieved by the typical two-drug combination therapy in the aforementioned literature. This indicates that the AEA+exercise regimen produces a more powerful effect than ordinary drug-drug combinations.

[0057] In terms of clinical translation potential, our approach may have a greater advantage. Compared to simply increasing the types and dosages of drugs, introducing exercise as a non-pharmacological intervention is expected to significantly reduce the risk of drug-induced side effects while improving treatment safety and patient adherence. Sildenafil and scopolamine mentioned in the aforementioned literature are both chemical drugs, and their combined use may pose an additive risk of side effects. Our 'AEA + Exercise' approach, however, offers a potentially safer and more sustainable new treatment paradigm.

[0058] As one of the main endocannabinoids, AEA can activate CB1 receptors to alleviate anxiety and regulate stress responses, and has shown regulatory and ameliorative effects in mood-related disorders such as obsessive-compulsive disorder and bipolar disorder. In this study, mice in the AEA+exercise group showed significantly prolonged struggle time and significantly enhanced escape awareness, indicating that the combination of AEA and exercise can synergistically enhance the activity of endocannabinoid signaling pathways, significantly strengthen the intervention effects on anxiety, stress response, compulsive behavior, and mood fluctuations, and effectively promote the improvement of psychological resilience and the recovery of overall mental health.

[0059] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any person skilled in the art can make various changes, modifications, substitutions and variations to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the claims and their equivalents.

Claims

1. A method for improving or modulating mood in a subject, characterized in that, The method comprises administering to a subject an effective amount of anandamide or a derivative thereof before, during, or after exercise.

2. The method of claim 1, wherein, The mood comprises anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

3. The method of claim 1 or 2, wherein the effective amount is 50 mg-2500 mg.

4. The method according to any one of claims 1 to 3, characterized in that, The subject is a human or a mammal.

5. The method according to any one of claims 1 to 4, characterized in that, The anandamide or a derivative thereof is formulated as a nutraceutical, a dietary supplement, a food, a beverage, or an animal feed.

6. The method according to any one of claims 1 to 5, characterized in that, The anandamide or a derivative thereof is prepared as a solid formulation or a liquid formulation.

7. The method according to any one of claims 1 to 6, characterized in that, The anandamide or a derivative thereof is in the form of a suppository, a tablet, a pill, a granule, a powder, a film, a capsule, a beverage, an aerosol, a spirit, a tincture, a tonic, a liquid suspension, a syrup.

8. The method according to any one of claims 1 to 7, characterized in that, The administration is by a route selected from the group consisting of oral, intravenous injection, intramuscular injection, intraperitoneal injection, or sublingual application.

9. A composition characterized in that, The use of anandamide or a derivative thereof in the manufacture of a medicament for improving or modulating a mood of a subject before, during, or after exercise.

10. The composition according to claim 9, characterized in that, The mood comprises anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

11. The composition according to claim 9 or 10, characterized in that, The amount of the composition is 50 mg-2500 mg.

12. The composition according to any one of claims 9-11, characterized in that, The composition is prepared as a solid formulation or a liquid formulation.

13. The composition according to any one of claims 9-12, characterized in that, The composition is formulated as a nutraceutical, a dietary supplement, a food, a beverage, or an animal feed.

14. The composition according to any one of claims 9-13, characterized in that, The composition is in the form of a suppository, a tablet, a pill, a granule, a powder, a film, a capsule, a beverage, an aerosol, a spirit, a tincture, a tonic, a liquid suspension, a syrup.

15. Use of anandamide or a derivative thereof in the preparation of a composition for improving or modulating mood in a subject, characterised in that, The use of anandamide or a derivative thereof in the manufacture of a medicament for improving or modulating a mood of a subject before, during, or after exercise.

16. Use according to claim 15, characterized in that, The mood comprises anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

17. Use according to claim 15 or 16, characterized in that, The amount of the composition is 50 mg-2500 mg.

18. Use according to any one of claims 15-17, characterized in that, The anandamide or a derivative thereof is prepared as a solid formulation or a liquid formulation.

19. Use according to any one of claims 15-18, characterized in that, The anandamide or a derivative thereof is in the form of a suppository, a tablet, a pill, a granule, a powder, a film, a capsule, a beverage, an aerosol, a spirit, a tincture, a tonic, a liquid suspension, a syrup.

20. The use according to any one of claims 15 to 19, characterized in that, The composition is used in the manufacture of a nutraceutical, a dietary supplement, a health food, a food, a beverage, an animal feed.

21. Use according to claim 20, characterized in that, The composition is in a weight ratio of 0.1-95%.

22. Use according to claim 20 or 21, characterized in that, The composition is in a weight ratio of 10-60%.

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