Amino acid composition and application thereof

Abstract

The present invention discloses an amino acid composition and its application. The amino acid composition of the present invention comprises tryptophan, glycine, pyroglutamic acid and L-alanyl-cyclo (L-glutamine), and its mass ratio is (1-20): (10-50): (0.1-3): (0.1-2.5). The amino acid composition has good antidepressant and antianxiety activity, can be used to alleviate and treat depression and anxiety, and provide parenteral nutrition support to postoperative patients. The amino acid composition has good stability and safety after being prepared into oral preparations and injection preparations.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and specifically relates to an amino acid composition and application thereof, in particular to application in anti-depression and anti-anxiety. Background Art

[0002] Depression and anxiety are two common mental disorders. The main manifestations of depression are obvious and persistent low mood, lack of energy, and physical and mental exhaustion, while the main manifestations of anxiety are excessive worry, tension, and fear. They are often accompanied by symptoms such as palpitations, difficulty concentrating, and sleep disorders. Currently, common antidepressant and anxiety drugs on the market include venlafaxine hydrochloride, duloxetine, escitalopram, fluoxetine, etc. Although these drugs can relieve symptoms to a certain extent, they are often accompanied by side effects, including insomnia, dizziness, headache, diarrhea, nausea, decreased appetite, increased appetite, changes in depressive symptoms, increased muscle tone, tremor, drowsiness, sensory inversion, visual impairment, tinnitus, palpitations, hot flashes, yawning, rash, sweating, etc., and their effects on some patients are limited. Summary of the Invention

[0003] To overcome the above-mentioned shortcomings of the prior art, the present invention provides an amino acid composition and its use. There is a correlation between amino acid levels and the severity of depression and anxiety. Therefore, the development of amino acid drugs as a means of treating depression and anxiety has great application prospects.

[0004] The first aspect of the present invention provides an amino acid composition, which contains tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo (L-glutamine) in a mass ratio of (1-20): (10-50): (0.1-3): (0.1-2.5).

[0005] Furthermore, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo (L-glutamine) is (5-15): (15-45): (0.5-1.5): (0.3-1).

[0006] Preferably, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is (8-12):(20-40):(0.8-1.2):(0.5-0.8).

[0007] More preferably, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is (10-12):(25-30):(1.0-1.2):(0.5-0.6).

[0008] Furthermore, the amino acid composition further comprises alanyl-(γ-glutamyl)-alanyl-glutamine.

[0009] Furthermore, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is (1-20):(10-50):(0.1-3):(0.1-2.5):(0.1-2.1).

[0010] Furthermore, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is (5-15):(15-45):(0.5-1.5):(0.3-1):(0.1-1.5).

[0011] Preferably, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is (8-12):(20-40):(0.8-1.2):(0.5-0.8):(0.2-0.9).

[0012] More preferably, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is (10-12):(25-30):(1.0-1.2):(0.5-0.6):(0.2-0.6).

[0013] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 20:50:0.1:0.1.

[0014] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 20:10:3:2.5.

[0015] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 1:50:3:0.1.

[0016] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 5:15:0.5:1.

[0017] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 15:45:1.5:1.

[0018] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 15:15:0.5:0.3.

[0019] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 8:20:1.2:0.8.

[0020] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 12:20:1.2:0.8.

[0021] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 12:40:0.8:0.5.

[0022] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 12:30:1:0.6.

[0023] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 10:30:1.2:0.5.

[0024] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is 12:25:1:0.6.

[0025] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is 1:10:3:0.1:2.1.

[0026] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is 20:50:0.1:2.5:0.2.

[0027] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is 5:45:1.5:0.3:0.1.

[0028] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is 10:30:1.2:0.5:0.4.

[0029] In some embodiments of the present invention, in the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is 8:20:0.8:0.8:0.9.

[0030] Furthermore, the amino acid composition further comprises one or more of valine, leucine, isoleucine, aspartic acid, phenylalanine, arginine, histidine, lysine, threonine, serine, proline, glutamic acid, alanine, acetyltyrosine, acetylcysteine, methionine, taurine, alanylglutamine, tyrosine, cystine, cysteine, or salts thereof.

[0031] Furthermore, the salt (ie, the salt of the above amino acid) is selected from one or more of hydrochloride, phosphate, acetate, malate, citrate, ascorbate, succinate, fumarate, and tartrate.

[0032] In some embodiments of the present invention, the amino acid composition further comprises valine, leucine, isoleucine, aspartic acid, phenylalanine, arginine, histidine, lysine acetate, threonine, serine, proline, glutamic acid, alanine, acetyltyrosine, acetylcysteine, methionine, taurine, and alanylglutamine.

[0033] Furthermore, the amino acid composition can be used in combination with other active ingredients (such as active ingredients of enteral or parenteral nutrition preparations).

[0034] Furthermore, the amino acid composition further comprises pharmaceutically acceptable excipients.

[0035] Furthermore, the pharmaceutically acceptable excipients are selected from the group consisting of: diluents, fillers, binders, disintegrants, lubricants, glidants, wetting agents, solvents, suspending agents, emulsifiers, sweeteners, flavoring agents, taste masking agents, colorants, anti-adhesives, humectants, chelating agents, plasticizers, antioxidants, preservatives, stabilizers, surfactants, buffers, solubilizers, cosolvents, pH regulators, cosolvents, granulating agents, viscosity enhancers, osmotic pressure regulators, adsorbents, foaming agents, defoaming agents, flocculants, dispersants, dispersants, and anti-caking agents.

[0036] Preferably, the pharmaceutically acceptable excipient is selected from the group consisting of: diluents, fillers, binders, disintegrants, lubricants, glidants, wetting agents, solvents, anti-adhesives, dispersants, dispersants, and pH regulators.

[0037] Furthermore, the pharmaceutically acceptable excipients include lactose, cross-linked polyvinylpyrrolidone, silicon dioxide, magnesium stearate, water for injection, pH regulator, Tween, span, starch, lactitol, mannitol, sorbitol, maltodextrin, gelatin, xanthan gum, carrageenan, guar gum, shellac, glycerin, castor oil, polyacrylic acid resin, polyethylene glycol, polysorbate, polyvinyl alcohol, carbomer, poloxamer, pullulan, hyaluronic acid, alginate, methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, microcrystalline cellulose sodium carboxymethyl starch, carboxymethyl cellulose calcium, acrylic resin, cyclamate, sucralose, aspartame, sucrose, citric acid, tartaric acid, malic acid, lactic acid, flavor, surfactant, osmotic pressure regulator or one or more.

[0038] Preferably, the medically acceptable excipients include one or more of lactose, cross-linked polyvinylpyrrolidone, silicon dioxide, magnesium stearate, water for injection, and a pH regulator.

[0039] Preferably, the pH adjuster includes one or more of hydrochloric acid, phosphoric acid, acetic acid, glacial acetic acid, malic acid, citric acid, lactic acid, ascorbic acid, succinic acid, fumaric acid, and tartaric acid.

[0040] Furthermore, the pH regulator adjusts the pH value of the amino acid composition system to 5.5-7.0.

[0041] Furthermore, the dosage form of the amino acid composition is an enteral dosage form or a parenteral dosage form.

[0042] Furthermore, the intestinal dosage form is an oral dosage form, which is selected from: tablets, capsules, granules, suspensions, solutions, mixtures, syrups, powders, powders, pellets, pills, tinctures, decoctions, wines, emulsions, lozenges, and suspensions.

[0043] Furthermore, the parenteral dosage form is an injection dosage form, which is selected from: injection solution and powder for injection.

[0044] In some embodiments of the present invention, the dosage form of the amino acid composition is an oral dosage form, particularly a tablet or capsule. When prepared into an oral dosage form (such as a tablet or capsule), the pharmaceutically acceptable excipient is selected from one or more of a filler, a disintegrant, a lubricant, and a binder, preferably one or more of lactose, crospovidone, silicon dioxide, and magnesium stearate.

[0045] In some embodiments of the present invention, the dosage form of the amino acid composition is an injection, particularly an injection. When prepared as an injection (such as an injection), the pharmaceutically acceptable excipient is water for injection and / or a pH regulator, preferably water for injection and / or glacial acetic acid.

[0046] In some embodiments of the present invention, the amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), lactose, crospovidone, silicon dioxide, and magnesium stearate.

[0047] In some embodiments of the present invention, the amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), alanyl-(γ-glutamyl)-alanyl-glutamine, lactose, cross-linked polyvinylpyrrolidone, silicon dioxide, and magnesium stearate.

[0048] In some embodiments of the present invention, the amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), water for injection, and glacial acetic acid.

[0049] In some embodiments of the present invention, the amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), alanyl-(γ-glutamyl)-alanyl-glutamine, valine, leucine, isoleucine, aspartic acid, phenylalanine, arginine, histidine, lysine acetate, threonine, serine, proline, glutamic acid, alanine, acetyltyrosine, acetylcysteine, methionine, taurine, alanylglutamine, water for injection, and glacial acetic acid.

[0050] The second aspect of the present invention provides a use of the amino acid composition described in the first aspect of the present invention in the preparation of a drug for preventing and / or treating depression, anxiety or insomnia.

[0051] Furthermore, the depression, anxiety or insomnia may be caused by various reasons, such as trauma or post-operatively.

[0052] The third aspect of the present invention provides a use of the amino acid composition described in the first aspect of the present invention in preparing a nutritional formulation.

[0053] Furthermore, the nutritional preparation may be an enteral dosage form or a parenteral dosage form.

[0054] In some embodiments of the present invention, the nutritional preparation is in the form of a parenteral dosage form, such as an injection solution.

[0055] Furthermore, the nutritional preparation can provide nutritional support to patients suffering from depression, anxiety or insomnia, and reduce the degree of depression and anxiety in the patients.

[0056] Furthermore, the depression, anxiety or insomnia may be caused by various reasons, such as trauma or post-operatively.

[0057] The fourth aspect of the present invention provides a use of the amino acid composition described in the first aspect of the present invention in preparing sleep-aiding food or health care products.

[0058] The fifth aspect of the present invention provides a method for preventing and / or treating depression, anxiety or insomnia, which comprises administering the amino acid composition of the first aspect of the present invention to a subject in need thereof.

[0059] Furthermore, the subject is a mammal, particularly a human.

[0060] Furthermore, the administration can be carried out by any suitable route of administration, such as gastrointestinal administration (such as oral, sublingual, rectal administration, etc.) or parenteral administration (such as intravenous, intramuscular, intranasal, intracerebral, intravaginal, intraperitoneal, transdermal, subcutaneous, intradermal, instillation, respiratory tract administration, etc.).

[0061] The present invention has the following beneficial effects:

[0062] (1) Compared with single-component amino acid drugs such as tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine, the amino acid composition of the present invention with a specific ratio has a better alleviating or therapeutic effect on depression, anxiety, and insomnia, and there is a synergistic effect between the components.

[0063] (2) After the amino acid composition of the present invention is prepared into a preparation (especially an oral preparation and an injectable preparation), it has excellent quality, good stability and safety.

[0064] (3) The amino acid composition of the present invention can provide nutritional support to postoperative patients and significantly reduce the patients' depression and anxiety levels. DETAILED DESCRIPTION

[0065] Unless otherwise defined, all scientific and technical terms used in the present invention have the same meanings as commonly understood by one of ordinary skill in the art to which the present invention relates.

[0066] In the amino acid composition of the present invention, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo (L-glutamine) can be a ratio formed by any point value selected from the numerical range. For example, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo (L-glutamine) is (1-20): (10-50): (0.1-3): (0.1-2.5), and the ratio of the four components can be any point value in the range of tryptophan 1-20 (for example, 1, 2 , 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, 20) and any point value between glycine 10-50 (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30). 9, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50) and any point value between 0.1 and 3 (e.g., 0.1, 0.2, 0.3, 0.4, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, 1.25) of pyroglutamic acid. , 1.3, 1.35, 1.4, 1.45, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3) and any point value between 0.1-2.5 of L-alanyl-cyclo(L-glutamine) (e.g., 0.1, 0.2, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.5, 2, 2.5).

[0067] In the amino acid composition of the present invention, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo (L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine can be a ratio formed by any point value selected from the numerical range. For example, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo (L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is (1-20): (10-50): (0.1-3): (0.1-2.5): (0.1-2.1), and the ratio of the five components can be any point value in the range of tryptophan 1-20 (for example, 1, 2, 3, 4, 5, 35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50) and any point value between 10-50 of glycine (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) and any point value between 10-50 of glycine (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) and any point value between 10-50 of glycine (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) and any point value between 10-50 of glycine (e.g., 10, 1 Any value between 0.1 and 3 for glutamic acid (e.g., 0.1, 0.2, 0.3, 0.4, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3) and any value between 0.1 and 2.5 for L-alanyl-cyclo(L-glutamine) (e.g., 0.1, 0.2, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0. 7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.5, 2, 2.5) and any point value between 0.1-2.1 of alanyl-(γ-glutamyl)-alanyl-glutamine (e.g., 0.1, 0.15, 0.2, 0.22, 0.24, 0.26, 0.28, 0.3, 0.32, 0.34, 0.36, 0.38, 0.4, 0.42, 0.44, 0.46, 0.48, 0.5, 0.52, 0.54, 0.56, 0.58, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 1, 1.5, 2, 2.1).

[0068] The term "pharmaceutically acceptable excipient" refers to an excipient that does not cause significant irritation to an organism and does not interfere with the biological activity and properties of the active ingredient (such as the amino acid composition of the present invention) being administered. Pharmaceutically acceptable excipients can be selected specifically according to the specific function in the composition. Pharmaceutically acceptable excipients include, but are not limited to: diluents, fillers, binders, disintegrants, lubricants, glidants, wetting agents, solvents, suspending agents, emulsifiers, sweeteners, flavoring agents, taste masking agents, colorants, anti-adhesives, wetting agents, chelating agents, plasticizers, antioxidants, preservatives, stabilizers, surfactants, buffers, solubilizers, cosolvents, pH regulators, cosolvents, granulating agents, viscosity-increasing agents, osmotic pressure regulators, adsorbents, foaming agents, defoaming agents, flocculants, dispersants, dispersants, anti-caking agents.

[0069] The amino acid composition of the present invention can be administered by any suitable route, such as gastrointestinal administration (such as oral, sublingual, rectal administration, etc.) or parenteral administration (such as intravenous, intramuscular, intranasal, intracerebral, intravaginal, intraperitoneal, transdermal, subcutaneous, intradermal, instillation, respiratory tract administration, etc.).

[0070] The amino acid composition of the present invention can be formulated into dosage forms suitable for administration to patients via the desired route, including but not limited to enteral dosage forms and parenteral dosage forms, specifically oral dosage forms (such as tablets, capsules, granules, suspensions, solutions, mixtures, syrups, powders, powders, pellets, pills, tinctures, decoctions, wines, emulsions, lozenges, suspensions, etc.), injectable dosage forms (such as injections, powders for injection, etc.), respiratory tract dosage forms (such as sprays, aerosols, powder aerosols, etc.), mucosal dosage forms (such as nasal drops, gargles, sublingual tablets, etc.), and cavity dosage forms (such as suppositories, aerosols, effervescent tablets, drops, pellets, etc.).

[0071] The formulations of the present invention can be divided into unit doses containing an appropriate amount of the active ingredient (e.g., the amino acid composition of the present invention), and the unit dosage form can be a tablet, capsule, injection, or any other dosage form. The amount of the active ingredient in the unit dose can be varied or adjusted from 0.1 mg to 1000 mg (e.g., 0.1, 1, 5, 10, 20, 40, 50, 100, 200, 400, 500, 1000 mg), depending on the specific application and efficacy of the active ingredient.

[0072] The terms "patient" or "subject" and the like are used interchangeably herein to refer to any animal or cell thereof to be treated according to the methods described herein, whether in vitro or in situ. Specifically, the aforementioned animals include mammals, e.g., rats, mice, guinea pigs, rabbits, dogs, monkeys or humans, particularly humans.

[0073] The term "treating" refers to preventing, curing, reversing, attenuating, alleviating, minimizing, inhibiting, suppressing and / or halting one or more clinical symptoms of a disease after onset of the disease.

[0074] The term "prevent" or "prevent" refers to treating a disease before it occurs to avoid, minimize, or make the onset or development of the disease more difficult.

[0075] The disclosures of various publications, patents, and published patent specifications cited herein are incorporated by reference in their entirety.

[0076] The chemical structure of "L-alanyl-cyclo(L-glutamine)" used in this example is shown below:

[0077]

[0078] The "alanyl-(γ-glutamyl)-alanyl-glutamine" used in this example is abbreviated as AlaGlu (AlaGln), and its chemical structure is shown below:

[0079] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts shall fall within the scope of protection of the present invention.

[0080] The experimental methods and materials involved in the following examples are as follows:

[0081] 1. Experimental Animals

[0082] Type and strain: ICR mice; Gender and number: 500 male mice; Weight: 20-30 g; Source: Pizhou Oriental Breeding Co., Ltd.; Grade: SPF grade.

[0083] Animals were housed in mice boxes containing bedding, 8 per cage. The animal room met SPF requirements, with controlled temperature of 20-26°C, humidity of 40-70%, lighting of 12h each, and noise level below 60dB.

[0084] Experimental environment: controlled temperature: 20-26℃; humidity: 40-70%; noise: below 60dB.

[0085] 2. Experimental instruments

[0086] 1 mL disposable sterile syringes were purchased from Henan Yakang Pharmaceutical Co., Ltd.;

[0087] A swimming straight cylinder (specifications: 25 cm in height and 10 cm in diameter) was purchased from Anhui Zhenghua Biological Instrument Co., Ltd.

[0088] Timer (model: ps-6100) was purchased from Shenzhen Zhuiri Technology;

[0089] Pipette (model: Pipet-Lite XLS, range: 1000 μL, 100 μL), purchased from Mettler Toledo;

[0090] Electronic balance (model: PWN8201ZH / E) was purchased from Changzhou Ohaus Instrument Co., Ltd.

[0091] The animal behavior experiment video analysis system and software (ANY-maze V7.0) were purchased from Grobel Biotech;

[0092] The mouse open field test box (specifications: 60 cm long, 60 cm wide, 30 cm high, divided into four equal cubes, with a gray polyethylene surround and a black polyethylene bottom) was purchased from Anhui Zhenghua Biological Instrument Co., Ltd.

[0093] Hikvision video recording system (H.265 series NVR) was purchased from Hangzhou Hikvision Digital Technology Co., Ltd.

[0094] 3. Drugs and reagents

[0095] Table 1: Drugs and reagents

[0096]

[0097]

[0098] 4. Mass ratio of each component in the amino acid composition

[0099] Tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine were weighed respectively according to the mass ratio shown in Table 2, and the components were evenly mixed to obtain the corresponding amino acid composition.

[0100] Table 2: Mass ratio of each component in the amino acid composition

[0101]

[0102]

[0103] Example 1: Antidepressant Activity Test of Amino Acid Drugs

[0104] 1. Construction of a mouse model of depression

[0105] The forced swimming test (FST) was used to induce a depression model in mice. When the mice stopped struggling and showed a state of "behavioral despair" (floating and motionless), the depression mouse model was successfully established.

[0106] 2. Forced swimming test

[0107] The antidepressant activity of amino acids and their combinations was evaluated by the forced swim test.

[0108] 2.1 Experimental steps:

[0109] (1) Before the experiment, adjust the water temperature in the test box to 23-25°C. The water depth should be adjusted according to the weight of the animal, and the animal's tail should be kept at a certain distance from the bottom of the test box.

[0110] (2) If multiple animals are tested simultaneously, an opaque barrier should be used to separate each pair of animals.

[0111] (3) Mice were randomly divided into a vehicle group (group 1), a positive drug control group (group 2), an amino acid single drug group (group 5), an amino acid combination group (group 17), and an amino acid comparison group (group 8), with 8 mice in each group. The vehicle group was given normal saline, and the drugs in the amino acid single drug group, the amino acid combination group, and the amino acid comparison group were prepared with normal saline solution and ultrasonicated for about 10 minutes.

[0112] (4) Each mouse was dosed at a volume of 0.1 ml / 10 g. The experiment was performed after the amino acid drugs were administered via the tail vein, and the other drugs were injected intraperitoneally.

[0113] (5) The forced swimming test for mice should be conducted on the day of testing. The forced swimming test should be started immediately after the mice are given normal saline. The forced swimming test should be conducted immediately 5 minutes after the mice are given amino acid drugs. The swimming time of the mice should be 6 minutes, and the immobility time after 4 minutes should be recorded.

[0114] 2.2 Evaluation indicators

[0115] Immobility time: The animal ceases struggling and floats in the water, with only slight limb movements to keep its head above the surface. Longer immobility times indicate more severe depression. Normal mice experience immobility time between 40% and 80% of the measured time. Depressive behavior is determined by a significant increase in immobility time compared to the vehicle group (i.e., model group) (P < 0.05).

[0116] 3. Experimental results

[0117] Compared with the vehicle group, at a dose of 100 mg / kg, tryptophan, glycine, and L-pyroglutamate in the amino acid single-drug group slightly showed the effect of reducing immobility time and increasing the desire to survive of mice, indicating that these three amino acids have antidepressant activity, but the antidepressant activity is low. L-alanine-cyclo(L-glutamine) and alanyl-(γ-glutamyl)-alanyl-glutamine did not show a reduction in immobility time, indicating that these two drugs have no antidepressant activity when used alone.

[0118] Compared with the positive drug control group, the antidepressant effect of amino acids alone was weaker than that of the positive drugs venlafaxine hydrochloride and duloxetine.

[0119] Compared to the vehicle group, amino acid compositions 1-17 significantly reduced the immobility time of mice in forced swimming and increased the mice's desire to survive, demonstrating that the amino acid compositions exhibited strong antidepressant activity, and that amino acid compositions 1-17 exhibited superior antidepressant activity to that of the active drug and comparative example 1-8. Detailed experimental data are shown in the table below.

[0120] In summary, the individual amino acid components of tryptophan, glycine, L-pyroglutamic acid, and L-alanine-cyclo(L-glutamine) all exhibited weaker efficacy compared to the positive drug. Combining these four components significantly increased their efficacy, exhibiting a synergistic effect relative to the activity of each component alone, and exhibited significantly higher antidepressant activity than both Comparative Examples 1-8 and the positive drug. Adding alanyl-(γ-glutamyl)-alanyl-glutamine to these four components unexpectedly further enhanced their antidepressant activity.

[0121] Table 3: Experimental results of antidepressant activity

[0122]

[0123]

[0124] Note: *, p < 0.05. **, p < 0.01, compared with the vehicle group. Each group consisted of 8 animals, and data are presented as mean ± standard deviation.

[0125] Example 2: Anxiolytic Activity Test of Amino Acid Drugs

[0126] 1. Construction of an anxiety disorder mouse model

[0127] Experimental mice were injected with meta-chlorophenylpiperazine (m-CPP), and an open field experiment was carried out. Behavioral analysis software was used to analyze the mice's behavioral indicators such as movement distance, movement speed, and rest time. When the mice's activity and exploratory behavior were inhibited, the anxiety disorder mouse model was successfully constructed.

[0128] 2. Open field experiment

[0129] The anxiolytic activity of amino acids and their combinations was evaluated by the open field test (OFT).

[0130] 2.1 Experimental steps

[0131] (1) Before the experiment, animals should be acclimatized to the testing environment for 30 to 60 minutes.

[0132] (2) The experimenter pre-sets the corresponding parameters in the ANY-maze software and records the animal's number, date, and status information.

[0133] (3) Mice were randomly divided into a vehicle group (1 group), a model group (1 group), a positive drug control group (2 groups), an amino acid single drug group (5 groups), an amino acid combination group (17 groups), and an amino acid comparison group (8 groups), with 8 mice in each group. The vehicle group was given normal saline, and the model group and the drug group were given a single intraperitoneal injection of m-chlorophenylpiperazine to induce anxiety in the mice. The drugs in the positive drug control group, the amino acid single drug group, the amino acid combination group, and the amino acid comparison group were prepared with normal saline solution and ultrasonicated for about 10 minutes.

[0134] (4) Each mouse was given the drug at a volume of 0.1 ml / 10 g. Amino acid drugs were administered via the tail vein, and other drugs were administered via intraperitoneal injection.

[0135] (5) Place the mice in an observation box with black walls and a black bottom. Divide the bottom of the box into 16 equal squares. Test four mice at a time for 5 minutes. Record the movement distance, movement time, number of center entries, and other related behavioral information.

[0136] (6) The animal should be placed in the center of the test box from the same position and direction each time.

[0137] 2.2 Evaluation indicators

[0138] (1) Total distance: The cumulative physical displacement of the animal during the experimental recording time.

[0139] (2) Traveling time: the cumulative time required for the animal to produce physical movement during the experimental recording time.

[0140] (3) Number of central cell crosses: This simply refers to the number of times the animal enters and exits the central cell. The cells or areas connected to the walls of the open field chamber are called peripheral cells, and the area not connected to the chamber walls is called the central cell. A decrease in the number of central cell crosses is associated with anxiety in mice.

[0141] 3. Experimental results

[0142] In terms of movement distance: Compared with the model group, in the amino acid single-drug group, except for L-alanine-cyclo-(L-glutamine) and alanyl-(γ-glutamyl)-alanyl-glutamine, the remaining amino acid single drugs at a dose of 100 mg / kg slightly increased the total movement distance of mice in the open field. Compared with the model group, at the same dose, amino acid combination 1-17 increased the movement distance of mice, enhanced the exercise ability of anxious mice in the open field, and increased the desire to explore. The movement distance of amino acid combination 1-17 was significantly better than that of the positive drug and comparative example 1-8.

[0143] In terms of exercise time: Compared with the model group, tryptophan, glycine, and L-pyroglutamate in the amino acid monotherapy group at a dose of 100 mg / kg can enhance the desire to exercise and increase the exercise time of anxious mice, but the effect is small; L-alanine-cyclo(L-glutamine) and alanyl-(γ-glutamyl)-alanyl-glutamine alone can hardly increase the exercise time of anxious mice. Compared with the model group, amino acid composition 1-17 can significantly increase the exercise time of anxious mice in the open field at the same dose, and the exercise time of amino acid composition 1-17 is better than that of the positive drug and comparative example 1-8.

[0144] In terms of the number of center entries: at the same dose, the number of center entries of the mice of the amino acid composition 1-17 increased compared with the model group, and the number of center entries was significantly greater than that of the single drug group, the positive drug and the comparative example 1-8.

[0145] The above experimental results show that tryptophan, glycine, and pyroglutamic acid have slight anxiolytic activity in the anxiety model induced by meta-chlorophenylpiperazine (m-CPP), but the activity is relatively low, while L-alanine-cyclo (L-glutamine) and alanyl-(γ-glutamyl)-alanyl-glutamine are not found to produce anxiolytic effects in mice. The anxiolytic effect of amino acid compositions 1-17 in different proportions is better, and can significantly increase the movement distance, movement time, and center entry number of mice in the open field, and is significantly better than comparative examples 1-8 and amino acid single drug groups and positive drugs in terms of movement distance, movement time, and center entry number. Detailed experimental data are shown in Table 4 below.

[0146] In summary, the individual amino acid components of tryptophan, glycine, L-pyroglutamic acid, and L-alanine-cyclo(L-glutamine) all exhibited weaker efficacy compared to the positive drug. Combining these four components significantly increased their efficacy, exhibiting a synergistic effect relative to the activity of each component alone, and exhibited significantly higher anxiolytic activity than both Comparative Examples 1-8 and the positive drug. Surprisingly, the addition of alanyl-(γ-glutamyl)-alanyl-glutamine to these four components further enhanced their anxiolytic activity.

[0147] Table 4: Experimental results of anxiolytic activity

[0148]

[0149]

[0150] Note: *, p < 0.05. **, p < 0.01 compared with the model group. The sample size for each group was 8, and the data were presented as mean ± standard deviation.

[0151] Example 3: Prescription and preparation of amino acid composition preparation

[0152] 1. Oral preparation of amino acid composition

[0153] 1.1 Amino Acid Composition Preparation A (Dispersible Tablets) Formulation and Preparation Method

[0154] Table 5: Formulation formula of amino acid composition preparation A (dispersible tablets)

[0155]

[0156] Preparation method:

[0157] (1) Weigh the prescribed amount (see Table 5) of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) (their mass ratio is shown in Composition 11 in Table 2), add the auxiliary materials lactose and cross-linked polyvinylpyrrolidone, mix, and sieve.

[0158] (2) Add the mixed material into a dry granulator for granulation and granulation.

[0159] (3) Add silicon dioxide, magnesium stearate, etc. to the granules and mix well.

[0160] (4) Tableting and packaging.

[0161] 1.2 Amino Acid Composition Preparation B (Capsule) Formulation and Preparation Method

[0162] Table 6: Formulation formula of amino acid composition preparation B (capsule)

[0163]

[0164] Preparation method:

[0165] (1) Weigh the prescribed amount (see Table 6) of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine (their mass ratio is shown in Composition 16 in Table 2), add the auxiliary materials lactose and cross-linked polyvinylpyrrolidone, mix, and sieve.

[0166] (2) Add the mixed material into a dry granulator for granulation and granulation.

[0167] (3) Add auxiliary materials such as silicon dioxide and magnesium stearate to the granules and mix well.

[0168] (4) Fill the granules into empty capsule shells and package.

[0169] 2. Injection of amino acid composition

[0170] 2.1 Amino Acid Composition Preparation C (Injection) Formulation and Preparation Method

[0171] Table 7: Formulation formula of amino acid composition preparation C (injection)

[0172]

[0173] Preparation method:

[0174] (1) Add 80-90% of the prescribed amount of water for injection (see Table 7) into the concentrated preparation tank, heat to boil, fill with nitrogen, and cool.

[0175] (2) Add the prescribed amount of glycine, pyroglutamic acid, L-alanyl-cyclo (L-glutamine), and tryptophan in sequence (their mass ratios are shown in Composition 11 in Table 2) and stir to dissolve.

[0176] (3) Filter the liquid and transfer it to a dilution tank, purging it with nitrogen. Adjust the pH to 5.5-7.0 with an appropriate amount of glacial acetic acid, add water for injection to the full volume, and stir well.

[0177] (4) Use two-stage 0.22 micron filter element for fine filtration and constant volume.

[0178] (5) Fill into glass infusion bottles.

[0179] (6) Sterilization.

[0180] 2.2 Amino Acid Composition Preparation D (Injection) Formulation and Preparation Method

[0181] Table 8: Formulation formula of amino acid composition preparation D (injection)

[0182]

[0183] Preparation method:

[0184] (1) Add 80-90% of the prescribed amount of water for injection (see Table 8) into the concentrated preparation tank, heat to boil, fill with nitrogen, and cool.

[0185] (2) Add the prescribed amount of valine, leucine, isoleucine, aspartic acid, phenylalanine, arginine, histidine, lysine acetate, threonine, serine, proline, glutamic acid, alanine, acetyltyrosine, acetylcysteine, methionine, glycine, taurine, alanylglutamine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), alanyl-(γ-glutamyl)-alanyl-glutamine, and tryptophan in sequence (wherein, the mass ratio of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine is shown in Composition 16 in Table 2), stir to dissolve, and adjust to volume.

[0186] (3) Filter the liquid and transfer it to a dilution tank, purging it with nitrogen. Adjust the pH to 5.5-7.0 with an appropriate amount of glacial acetic acid, add water for injection to the full volume, and stir well.

[0187] (4) Use two-stage 0.22 micron filter element for fine filtration.

[0188] (5) Fill into glass infusion bottles.

[0189] (6) Sterilization.

[0190] Example 4: Stability test of amino acid composition preparation

[0191] With reference to the method of the guidance for stability testing of pharmaceutical preparations in the Chinese Pharmacopoeia, the amino acid composition preparations A, B, C and D prepared in Example 3 were placed at 40°C + 2°C and a relative humidity of 75% + 5%, and samples were taken in 0 month, 1 month, 2 month, 3 month and 6 month, respectively, to examine their appearance, properties, active ingredient content, impurities, solubility, dispersion uniformity, clarity, pH value, sterility test and other aspects.

[0192] The experimental results are shown in Tables 9-12 below. It can be seen that after 6 months of long-term testing, there was no significant change in the appearance, properties, active ingredient content, solubility, dispersion uniformity, clarity, pH value and sterility test indicators of this product. All indicators met the relevant provisions of the production quality standards and the product had good stability.

[0193] Table 9: Stability test results of amino acid composition preparation A (dispersible tablets)

[0194]

[0195]

[0196] Table 10: Stability test results of amino acid composition preparation B (capsules)

[0197]

[0198] Table 11: Stability test results of amino acid composition preparation C (injection)

[0199]

[0200] Table 12: Stability test results of amino acid composition preparation D (injection)

[0201]

[0202]

[0203] Example 5: Efficacy and safety test of amino acid composition preparation D in antidepressant, antianxiety and parenteral nutrition support for postoperative patients

[0204] 1. Experimental Design

[0205] A randomized, double-blind, parallel controlled trial was conducted to evaluate the effectiveness and safety of amino acid composition preparation D (injection) (prepared by Example 3) in anti-depression, antianxiety and parenteral nutrition support for postoperative patients.

[0206] Inclusion criteria: (1) age 18-75 years, weight 45-75 kg; (2) patients undergoing elective gastrectomy, small bowel resection, or colorectal resection (including laparoscopy), requiring postoperative parenteral nutrition, and comorbid with anxiety and depression; (3) nutritional screening NRS2002 score ≥ 3; Exclusion criteria: (1) patients who had received anti-anxiety or antidepressant medication before enrollment; (2) patients with congenital amino acid metabolic abnormalities or allergies to amino acids, fat emulsions, soy, etc. A total of 10 postoperative patients were included, with 5 subjects in the study group and 5 subjects in the control group, with an average age of 48.23±7.67 years and 46.37±8.26 years, respectively.

[0207] The study group received intravenous infusion of a total intravenous nutrition preparation containing amino acid composition preparation D (equivalent to 1.25g / kg / d of amino acids) once a day for 5 consecutive days; the control group received intravenous infusion of a total intravenous nutrition preparation containing 8.5% compound amino acids (18AA-II) (purchased from Anhui Fubon Pharmaceutical, equivalent to 1.25g / kg / d of amino acids) once a day for 5 consecutive days. At the same time, psychological counseling intervention was performed on both groups of patients.

[0208] 2. Efficacy indicators

[0209] (1) Main efficacy indicators:

[0210] A. Comparison of nutritional indicators between the two groups of patients on D1, D3, and D7 after perioperative period, including prealbumin (PA), total protein (TP), and albumin (ALB) levels.

[0211] B. The Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to evaluate the psychological status of the two groups of patients on D1, D3, and D7 after the operation, and the HAMA and HAMD scores of the two groups of patients after nursing were compared.

[0212] Hamilton Depression Scale (HAMD): no depression: less than 7 points, mild depression: 7-16 points, moderate depression: 17-24 points, severe depression: more than 24 points.

[0213] The Hamilton Anxiety Scale (HAMA) showed no anxiety <7 points, possible anxiety 7-12 points, anxiety 14-23 points, marked anxiety 24-29 points, and severe anxiety >29 points.

[0214] (2) Secondary efficacy indicators:

[0215] The occurrence of adverse reactions (vomiting, postoperative infection, wound dehiscence, abdominal distension, etc.).

[0216] 3. Test results

[0217] As shown in Table 13 below, before treatment, there was no statistically significant difference in the PA, TP, and ALB nutritional index levels between the two groups of patients (all P>0.05); 7 days after treatment, the above nutritional index levels of the two groups of patients were significantly increased compared with those before treatment (all P<0.05), but there was no significant difference compared with the control group (P>0.05).

[0218] As shown in Table 14 below, on D1 after surgery, the HAMD score of the control group was 10.68±3.28, and the HAMD score of the study group was 11.58±3.61, with no significant difference. On D3 after surgery, the HAMD score of the control group was 8.91±2.19, and the HAMD score of the study group was 5.79±2.58. Compared with D1, the score of the control group did not change significantly, but the score of the study group decreased significantly. On D7 after surgery, the HAMD score of the control group was 7.94±1.01, and the HAMD score of the study group was 2.23±0.83, with a significant difference (P<0.05).

[0219] As shown in Table 15 below, on D1 after surgery, the HAMA score of the control group was 10.25±3.01, and the HAMA score of the study group was 11.79±3.77, with no significant difference. On D3 after surgery, the HAMD score of the control group was 9.55±2.14, and the HAMD score of the study group was 6.28±2.83. Compared with D1, the score of the control group did not change significantly, but the score of the study group decreased significantly. On D7 after surgery, the HAMA score of the control group was 8.79±1.23, and the HAMA score of the study group was 3.21±0.96, with a significant difference (P<0.05).

[0220] Secondary efficacy indicators: No adverse reactions occurred in both the study group and the control group.

[0221] Table 13: Comparison of perioperative nutritional indicators between the two groups of patients (Mean ± sem)

[0222]

[0223] Note: *, p < 0.05, compared with D1, data are shown as mean ± standard deviation.

[0224] Table 14: HAMD score of depression level after perioperative period (Mean±sem)

[0225]

[0226] Note: *, p < 0.05, compared with D1, data are shown as mean ± standard deviation.

[0227] Table 15: HAMA score of anxiety level after perioperative period (Mean±sem)

[0228]

[0229] Note: *, p < 0.05, compared with D1, data are shown as mean ± standard deviation.

[0230] After the perioperative period, the nutritional index levels of the patients in the study group and the control group were significantly higher than those before treatment (P<0.05), but there was no significant difference between the two (P>0.05). Both groups were able to provide postoperative nutritional support for the patients, and no adverse events occurred. On the first day after the perioperative period, the HAMD and HAMA scores of the study group and the control group showed that the patients had mild depression and anxiety, with no significant difference; on the third day, the depression and anxiety scores of the study group were significantly relieved, but the changes in the control group were not significant; on the seventh day, the patients in the study group had returned to normal, but the patients in the control group were still depressed and anxious, with a significant difference (P<0.05). The results showed that amino acid composition preparation D can provide nutritional support for patients after the perioperative period, and can significantly reduce the patients' depression and anxiety levels, proving that amino acid composition preparation D has anti-anxiety and anti-depression effects.

[0231] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

[0232] The aforementioned embodiments and methods described in the present invention may be varied based on the ability, experience, and preference of those skilled in the art.

[0233] In the present invention, merely listing the steps of the method in a certain order does not constitute any limitation on the order of the method steps.

Claims

1. An amino acid composition, comprising tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) in a mass ratio of (1-20):(10-50):(0.1-3):(0.1-2.5).

2. The amino acid composition according to claim 1, characterized in that In the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is (5-15):(15-45):(0.5-1.5):(0.3-1).

3. The amino acid composition according to claim 2, characterized in that In the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is (8-12):(20-40):(0.8-1.2):(0.5-0.8).

4. The amino acid composition according to claim 3, characterized in that In the amino acid composition, the mass ratio of tryptophan, glycine, pyroglutamic acid, and L-alanyl-cyclo(L-glutamine) is (10-12):(25-30):(1.0-1.2):(0.5-0.6).

5. The amino acid composition according to claim 1, characterized in that The amino acid composition further comprises alanyl-(γ-glutamyl)-alanyl-glutamine.

6. The amino acid composition according to claim 5, characterized in that In the amino acid composition, the mass ratios of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine are (1-20):(10-50):(0.1-3):(0.1-2.5):(0.1-2.1).

7. The amino acid composition according to claim 6, characterized in that In the amino acid composition, the mass ratios of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine are (5-15):(15-45):(0.5-1.5):(0.3-1):(0.1-1.5).

8. The amino acid composition according to claim 7, characterized in that In the amino acid composition, the mass ratios of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine are (8-12):(20-40):(0.8-1.2):(0.5-0.8):(0.2-0.9).

9. The amino acid composition according to claim 8, characterized in that In the amino acid composition, the mass ratios of tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), and alanyl-(γ-glutamyl)-alanyl-glutamine are (10-12):(25-30):(1.0-1.2):(0.5-0.6):(0.2-0.6).

10. The amino acid composition according to any one of claims 1 to 9, characterized in that The amino acid composition further comprises one or more of valine, leucine, isoleucine, aspartic acid, phenylalanine, arginine, histidine, lysine, threonine, serine, proline, glutamic acid, alanine, acetyltyrosine, acetylcysteine, methionine, taurine, alanylglutamine, tyrosine, cystine, cysteine, or salts thereof.

11. The amino acid composition according to claim 10, characterized in that The salt is selected from one or more of phosphate, acetate, malate, citrate, ascorbate, succinate, fumarate and tartrate.

12. The amino acid composition according to any one of claims 1 to 9, characterized in that The amino acid composition is used in combination with other active ingredients.

13. The amino acid composition according to any one of claims 1 to 9, characterized in that The amino acid composition further comprises a pharmaceutically acceptable excipient.

14. The amino acid composition according to claim 13, characterized in that The dosage form of the amino acid composition is an enteral dosage form or a parenteral dosage form.

15. The amino acid composition according to claim 14, characterized in that The intestinal dosage form is an oral dosage form, which is selected from the group consisting of tablets, capsules, granules, suspensions, solutions, mixtures, syrups, powders, powders, pills, tinctures, decoctions, wines, emulsions, and lozenges.

16. The amino acid composition according to claim 14, characterized in that The intestinal tract administration dosage form is a dropping pill.

17. The amino acid composition according to claim 14, characterized in that The parenteral dosage form is an injection dosage form, which is selected from: injection solution and powder for injection.

18. The amino acid composition according to claim 13, characterized in that The dosage form of the amino acid composition is tablet, capsule and injection.

19. The amino acid composition according to claim 13, characterized in that The dosage form of the amino acid composition is an oral dosage form, and the pharmaceutically acceptable excipient is selected from one or more of a filler, a disintegrant, a lubricant, and a binder.

20. The amino acid composition according to claim 13, characterized in that The dosage form of the amino acid composition is an injection dosage form, and the pharmaceutically acceptable excipients are water for injection and / or a pH regulator.

21. The amino acid composition according to claim 13, characterized in that The amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo (L-glutamine), lactose, cross-linked polyvinylpyrrolidone, silicon dioxide and magnesium stearate.

22. The amino acid composition according to claim 13, characterized in that The amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), alanyl-(γ-glutamyl)-alanyl-glutamine, lactose, cross-linked polyvinylpyrrolidone, silicon dioxide and magnesium stearate.

23. The amino acid composition according to claim 13, characterized in that The amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo (L-glutamine), water for injection and glacial acetic acid.

24. The amino acid composition according to claim 13, characterized in that The amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo(L-glutamine), alanyl-(γ-glutamyl)-alanyl-glutamine, valine, leucine, isoleucine, aspartic acid, phenylalanine, arginine, histidine, lysine acetate, threonine, serine, proline, glutamic acid, alanine, acetyltyrosine, acetylcysteine, methionine, taurine, alanylglutamine, water for injection, and glacial acetic acid.

25. Use of the amino acid composition according to any one of claims 1 to 24 in the preparation of a drug for preventing and / or treating depression, anxiety or insomnia.

26. The use according to claim 25, characterized in that The depression, anxiety or insomnia is caused by trauma or surgery.

27. Use of the amino acid composition according to any one of claims 1 to 24 in preparing a nutritional formulation.

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