AU2021104016A4 - Nmn composition for regulating emotion and relieving depression and use thereof - Google Patents
Nmn composition for regulating emotion and relieving depression and use thereof Download PDFInfo
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- 239000000203 mixture Substances 0.000 title claims abstract description 38
- 230000001105 regulatory effect Effects 0.000 title claims abstract description 13
- 230000008451 emotion Effects 0.000 title claims abstract description 11
- DATAGRPVKZEWHA-YFKPBYRVSA-N N(5)-ethyl-L-glutamine Chemical compound CCNC(=O)CC[C@H]([NH3+])C([O-])=O DATAGRPVKZEWHA-YFKPBYRVSA-N 0.000 claims abstract description 22
- DAYLJWODMCOQEW-TURQNECASA-N NMN zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)([O-])=O)O2)O)=C1 DAYLJWODMCOQEW-TURQNECASA-N 0.000 claims abstract description 14
- DATAGRPVKZEWHA-UHFFFAOYSA-N L-gamma-glutamyl-n-ethylamine Natural products CCNC(=O)CCC(N)C(O)=O DATAGRPVKZEWHA-UHFFFAOYSA-N 0.000 claims abstract description 11
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
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- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
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- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 9
- 229960003638 dopamine Drugs 0.000 abstract description 5
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 abstract description 3
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- 230000002708 enhancing effect Effects 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract description 2
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- 238000012827 research and development Methods 0.000 abstract description 2
- 230000001737 promoting effect Effects 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 21
- 230000000638 stimulation Effects 0.000 description 9
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 6
- 229960002464 fluoxetine Drugs 0.000 description 6
- 238000003304 gavage Methods 0.000 description 6
- 230000009182 swimming Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
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- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000012346 open field test Methods 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
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- 239000002775 capsule Substances 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 206010012374 Depressed mood Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 235000017309 Hypericum perforatum Nutrition 0.000 description 1
- 244000141009 Hypericum perforatum Species 0.000 description 1
- 241000872198 Serjania polyphylla Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010042458 Suicidal ideation Diseases 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
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- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
- 229960001848 lamotrigine Drugs 0.000 description 1
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- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
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- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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Abstract
The present application relates to the field of research and development of the
nutritional supplement, and in particular, relates to an NMN composition for
regulating emotion and relieving depression which comprises NMN, y-aminobutyric
acid and L-theanine. The composition makes people feel happy both physically and
mentally by inhibiting the entry of the anxiety information into the nerve centre using
the y-aminobutyric acid firstly, then increasing the content of NAD+ in vivo, thereby
improving the energy level of nerve cells and enhancing excitability and endurance
thereof using NMN, and promoting the release of dopamine in brain center using
L-theanine finally. The present application provides a composition for relieving
depression in an all-round way aiming at multiple links through the organic
coordination of the three components which is safe in ingredients with no toxic and
side effects and has significant effect on regulating emotion and relieving depression.
Description
Field of the Application
The present application relates to the field of research and development of the nutritional supplement, and in particular, relates to an NMN composition for regulating emotion and relieving depression and use thereof.
Background of the Application
Depression, also known as depressive disorder, has the main clinical symptoms of significant and persistent depressed mood. Depression is the main type of mental disorder. Patients with severe depression have suicidal tendency, which causes a series of major family problems, social problems and economic losses.
At present, antidepressants are generally western medicines, and three kinds of which as follows are commonly used: the first are drugs based on monoamine hypothesis such as fluoxetine; the second are drugs based on HPA axis dysfunction such as desipramine; the third are drugs based on amino acids and peptides such as lamotrigine. The above antidepressants have definite curative effects while there are also some defects such as strong toxic and side effects, easy to cause drug dependence and relapse of patients' condition.
Summary of the Application
In order to solve the above problems, the present application provides a safe NMN composition with no toxic and side effects for regulating emotion and relieving depression and use thereof. Technical solutions of the present application are as follows:
An NMN composition is provided, for regulating emotion and relieving depression, mainly comprising NMN, y-aminobutyric acid and L-theanine.
Furthermore, the composition comprises 3-22 parts of NMN, 10-40 parts of y-aminobutyric acid and 5-30 parts of L-theanine in parts by weight.
Preferably, the composition comprises 5-20 parts of NMN, 12-35 parts of y-aminobutyric acid and 10-25 parts of L-theanine in parts by weight.
Furthermore, the composition also comprises an excipient, which is selected from any one or more of the group consisting of mannitol, erythritol, microcrystalline cellulose, xylitol, crosslinked sodium carboxymethyl cellulose, pregelatinized starch, silicon dioxide, lactose, neurostan (i.e. the extract of St. John's wort), withania somnfera extracts, phosphatidylserine, S-adenosyl-L-methionine, magnesium stearate and gastric coating agents.
The present application further provides use of the agent containing any one of the above NMN composition in regulating emotion and relieving depression.
Compared with the prior art, the beneficial effects of the present application are as follows:
(1) y-aminobutyric acid is the main inhibitory neurotransmitter in the brain, which can inhibit the entry of the anxiety information into the nerve centre and sedate the nerves by regulating the content of NO in the frontal cortex to take an anti-anxiety effect. NAD+ can increase the vitality of dopamine cells and help alleviate the decrease of dopamine secretion. Taking nicotinamide mononucleotide (i.e.NMN) can increase the content of NAD+ in vivo, thereby improving the energy level of nerve cells and enhancing excitability and endurance thereof. L-theanine can regulate brain waves, promote the release of dopamine in brain center, and increase the physiological activity of dopamine in the brain.
(2) The present application provides a composition for regulating emotion and relieving depression in an all-round way aiming at multiple links by using the above three components which take effect synergistically. The composition has safe ingredients with no toxic and side effects and fills the gaps in current nutritional supplements for regulating mood and relieving depression.
Detailed Description of the Embodiments
Hereinafter, the present application will be described in detail with reference to the specific examples in order to make the content of the present application clear to be understood easily.
Example
10 parts by weight of NMN, 40 parts by weight of y-aminobutyric acid and 10 parts by weight of L-theanine were crushed and then passed through a 60-80 mesh sieve separately, and then mixed at a rotate speed of 20r/min for 20 minutes. After that, excipients of neurostan, mannitol, microcrystalline cellulose and magnesium stearate of appropriate amount were added into the above mixture after passed through a 60-80 mesh sieve and mixed at a rotate speed of 20r/min for 40 minutes. Then the obtained mixture were sent to a tablet press for tableting to obtain composition 1.
20 parts by weight of NMN, 10 parts by weight of y-aminobutyric acid and 30 parts by weight of L-theanine were crushed and then passed through a 60-80 mesh sieve separately, and then mixed at a rotate speed of 20r/min for 20 minutes. After that, excipients of withania somnfera extracts, erythritol, silicon dioxide and magnesium stearate of appropriate amount were added into the above mixture after passed through a 60-80 mesh sieve and mixed at a rotate speed of 20r/min for 40 minutes. Then the obtained mixture were sent to a capsule filling machine for capsule filling to obtain composition 2.
Experimental example
SPF SD rats weighing 200-250g were purchased from the Laboratory Animal Center of Nanjing Medical University. They were fed normally for one week to adapt to the environment firstly. Then the behavior score was evaluated by the open field test. After that, 50 rats with similar scores were selected and randomly divided into 5 groups including normal group, depression group, group fed with Fluoxetine, example composition 1 group and example composition 2 group with 10 rats in each group.
Then the following experiments were carried out, wherein:
(1) Normal group: the rats were fed in groups in two cages with 5 rats in each cage and kept in isolation from rats of other groups, and the rats were fed feed and drinking water as needed normally without any stimulation;
(2) Depression group: the rats were fed in single cage separately and received one different chronic stress stimulation which included 7 ways of ice water swimming, tail suspension, water prohibition, electric shock, tail clamping, all night lighting and fasting every day for 56 days. Each stimulation was used for 8 times but not used in two consecutive days, so that the rats could not predict the stimulation that would occur. After 28 days, normal saline of 1ml was administered to rats by gavage every day, and the stimulation continued during the gavage;
(3) group fed with Fluoxetine: the feeding environment and ways of stimulation were the same as those of Depression group. After 28 days, fluoxetine was administered to rats by gavage at the dose of 2.5mg/kg body weight daily, and the stimulation continued during the gavage;
(4) example groups: the feeding environment and ways of stimulation were the same as those of Depression group. After 28 days, the compositions described in Example 1 and Example 2 were administered to the corresponding group rats by gavage at the dose of 2.5mg/kg body weight daily, and the stimulation continued during the gavage.
Open Field Test: the length, width and height of the open box were all 80cm and the inner wall and bottom surface of the box were painted black with the bottom surface divided into 25 squares of equal area. The rat was placed in the middle of the open box, and the number of squares on the bottom surface that the rat passed through was taken as the score of horizontal movement, in which one score was obtained when passed through one square while the standing times of feet off the ground were taken as the vertical score in which one score was obtained when feet were off the ground once. The measuring time was 3 minutes. The measurement was performed once on the 3rd, 28th and 56th day of the experiment and then comparing the differences in the scores of each group. The index can reflect the activity of rats and their curiosity about the fresh environment, in which the horizontal movement reflects the level of motor activity and the vertical movement reflects their curiosity about the fresh environment. The results are shown in Table 1 indicating that the depressive performances of rats were alleviated after taking the composition of the present application.
Table 1 results of the score in the Open Field Test
groups 3d 28d 56d
normal group 57.3±2.9 54.9±3.1 55.2±2.5
depression group 54.8±2.2 31.5±2.7** 27.1±2.2**
group fed with 55.9±4.2 29.6±3.4** 50.7±3.6
Fluoxetine
example 53.7±3.1 32.7±1.9** 39.9±2.0*
composition 1 group
example 55.6±4.2 31.9±2.8** 37.8±1.8*
composition 2 group
Note: *means P<0.05, ** means P<0.01.
Determination of swimming immobility time in the Forced Swimming Test: the length and width of the water tank were both 25cm and the height was 40cm. The rats were put into the water tank, and then they firstly struggled to escape after which they were in a state of immobility. The state of immobility refers to the state in which rats stop struggling in the water and are in a state of floating immobility with occasionally performing limb activities so as to keep their heads floating on the water, which is called "behavioral despair". The swimming immobility time of each rat was accumulated within 5 minutes. The measurement was performed once on the 3rd, 28th and 56th day of the experiment. The index can reflect the degree of despair of the rats. The results are shown in Table 2 indicating that the despair of the rats were alleviated after taking the composition of the prevent application.
Table 2 results of the determination of swimming immobility time groups 3d 28d 56d normal group 45.1±2.6 45.3±2.6 46.1±1.8 depression group 43.8±3.1 64.2±3.3* 70.8±4.1** group fed with 44.6±1.8 66.7±2.1** 49.9±3.4 Fluoxetine example composition 46.0±3.3 62.5±3.9** 57.5±2.7 1 group example composition 44.9±2.6 65.8±4.0** 60.4±2.7 2 group
Note: *means P<0.05, ** means P<0.01.
The above disclosure only describes the preferred examples of the present application. However, the present application is not limited to specific details in the above embodiments. All technical solutions under the idea of the present application are within the scope of protection of the present application. It should be pointed out that for those skilled in the art, improvements and modifications without departing from the principle of the present application should all be regarded as within the scope of protection of the present application.
Claims (5)
1. An NMN composition for regulating emotion and relieving depression, wherein the composition comprises NMN, y-aminobutyric acid and L-theanine.
2. The NMN composition according to claim 1, wherein the composition comprises 3-22 parts of NMN, 10-40 parts of y-aminobutyric acid and 5-30 parts of L-theanine in parts by weight.
3. The NMN composition according to claim 2, wherein the composition
comprises 5-20 parts of NMN, 12-35 parts of y-aminobutyric acid and 10-25 parts of L-theanine in parts by weight.
4. The NMN composition according to any one of claims 1 to 3, wherein the
composition also comprises an excipient; wherein the excipient is selected from any one or more of the group consisting of mannitol, erythritol, microcrystalline cellulose, xylitol, crosslinked sodium carboxymethyl cellulose, pregelatinized starch, silicon dioxide, lactose, neurostan, withania somnfera extracts, phosphatidylserine, S-adenosyl-L-methionine, magnesium stearate and gastric coating agents.
5. Use of the agent containing the NMN composition according to any one of claims 1 to 3 in regulating emotion and relieving depression.
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