Amino acid composition and application thereof

Abstract

The invention discloses an amino acid composition and application thereof. The amino acid composition disclosed by the invention is prepared from tryptophan, glycine, pyroglutamic acid and L-alanyl-ring (L-glutamine), wherein the mass ratio of the tryptophan to the glycine to the pyroglutamic acid to the L-alanyl-ring (L-glutamine) is (1 to 20) to (10 to 50) to (0.1 to 3) to (0.1 to 2.5). The amino acid composition has good anti-depression and anti-anxiety activity, can be used for relieving and treating depression and anxiety, and provides parenteral nutrition support for postoperative patients. The amino acid composition has good stability and safety after being prepared into an oral preparation and an injection preparation.

Description

Technical Field

[0001] The 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 vitality, and physical and mental fatigue. 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. At present, the common antidepressant and anxiety drugs on the market are 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 tension, tremor, drowsiness, sensory perversion, visual impairment, tinnitus, palpitations, hot flashes, yawning, rash, sweating, etc., and the effect on some patients is limited. Summary of the invention

[0003] To overcome the defects of the prior art, the present invention provides an amino acid composition and its application. There is a certain relationship between the content level of amino acids 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 also contains 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 also 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 also contains pharmaceutically acceptable excipients.

[0035] Furthermore, the pharmaceutically acceptable excipients are selected from: diluents, fillers, binders, disintegrants, lubricants, glidants, wetting agents, solvents, suspending agents, emulsifiers, sweeteners, flavoring agents, 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-adhesive agents, dispersants, and pH regulators.

[0037] Furthermore, the pharmaceutically acceptable excipients include lactose, cross-linked polyvinylpyrrolidone, silicon dioxide, magnesium stearate, water for injection, pH adjusters, 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, calcium carboxymethyl cellulose, acrylic resin, cyclamate, sucralose, aspartame, sucrose, citric acid, tartaric acid, malic acid, lactic acid, flavors, surfactants, and one or more osmotic pressure regulators.

[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 adjuster.

[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 tablets and capsules. When prepared into an oral dosage form (such as tablets or capsules), 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, cross-linked polyvinylpyrrolidone, silicon dioxide, and magnesium stearate.

[0045] In some embodiments of the present invention, the dosage form of the amino acid composition is an injection dosage form, particularly an injection solution. When prepared as an injection dosage form (such as an injection solution), 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, cross-linked polyvinylpyrrolidone, 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-surgery.

[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 the preparation of a nutritional preparation.

[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 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 of the patients.

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

[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 the preparation of sleep-aiding food or health care product.

[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), alanyl-(γ-glutamyl)-alanyl-glutamine, etc., 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 injection preparation), it has excellent quality, good stability and safety.

[0064] (3) The amino acid composition of the present invention can provide nutritional support for postoperative patients and can 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 of pyroglutamic 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 L-alanyl-cyclic (L-glutamine) 0.1-2.5 (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), then the ratio of the five components can be any point value in 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 10-50 of glycine (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 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 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 Any value between 0.1 and 3 for glutamate (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, 0.75, 0.8 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 stimulation to an organism and does not interfere with the biological activity and properties of the administered active ingredient (such as the amino acid composition of the present invention). Pharmaceutically acceptable excipients can be selected specifically according to the specific functions in the composition. Pharmaceutically acceptable excipients include, but are not limited to: diluents, fillers, adhesives, disintegrants, lubricants, glidants, wetting agents, solvents, suspending agents, emulsifiers, sweeteners, flavoring agents, 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, defoamers, 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 dosage forms (such as sprays, aerosols, powder mists, etc.), mucosal dosage forms (such as nasal drops, gargles, sublingual tablets, etc.), cavity dosage forms (such as suppositories, aerosols, effervescent tablets, drops, pellets, etc.).

[0071] The preparation of the present invention can be divided into unit doses containing an appropriate amount of active ingredient (such as the amino acid composition of the present invention), and the unit dosage form can be tablets, capsules, injections or any dosage form. The amount of the active ingredient in the unit dose can be changed 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 term "patient" or "subject" and the like are used interchangeably herein and refer to any animal or cell thereof treated according to the methods described herein, whether in vitro or in situ. Specifically, the aforementioned animal includes 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" refers to avoiding, minimizing or making the onset or development of a disease difficult by treating it before it occurs.

[0075]

[00136] Various publications, patents, and published patent specifications are cited herein, the disclosures of which are incorporated by reference in their entireties.

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

[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 technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments 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 creative work are 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; Body weight: 20-30 g; Source: Pizhou Oriental Breeding Co., Ltd.; Grade: SPF grade.

[0083] Feeding and management: Animals were kept in mouse boxes with bedding, 8 per cage. The animal room met the SPF grade requirements, with controlled temperature: 20-26℃; humidity: 40-70%; lighting: 12h each for light and dark; noise: below 60dB.

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

[0085] 2. Experimental instruments

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

[0087] The 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), 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), 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 4 equal cubes, with gray polyethylene surrounding and 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 mouse depression model was induced by the forced swimming test (FST). When the mice stopped struggling and showed a state of "behavioral despair" (floating and motionless state), the depression mouse model was successfully constructed.

[0106] 2. Forced swimming test

[0107] The antidepressant activity of amino acids and their combinations was evaluated by the forced swimming 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 being tested simultaneously, an opaque barrier should be used to separate every two animals.

[0111] (3) The 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 ultrasound was performed 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 drug was administered via tail vein, and the other drugs were injected intraperitoneally.

[0113] (5) The forced swimming test for mice should be conducted on the day of the test. The forced swimming test should be started immediately after the mice are given 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] Immobile time: The animal stops struggling in the water and floats, with only slight limb movements to keep the head above the water. The longer the immobile time, the more severe the depression. The immobile time of normal mice is within 40% to 80% of the detection time; Depression behavior judgment criteria: The immobile time is significantly increased compared with the solvent 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 monotherapy group slightly showed the effect of reducing the 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, while L-alanine-cyclo(L-glutamine) and alanyl-(γ-glutamyl)-alanyl-glutamine did not show a reduction in immobility time, indicating that the 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 with the vehicle group, amino acid composition 1-17 significantly reduced the immobility time of mice in forced swimming and increased the survival desire of mice, which indicates that the amino acid composition has strong antidepressant activity, and the antidepressant activity of amino acid composition 1-17 is better than that of positive drugs and comparative examples 1-8. Detailed experimental data are shown in the table below.

[0120] In summary, the efficacy of the single amino acid components of tryptophan, glycine, L-pyroglutamic acid, and L-alanine-cyclo (L-glutamine) is weaker than that of the positive drug; after combining the above four components, the efficacy is significantly increased, with a synergistic effect relative to the activity of each single component, and its antidepressant activity is significantly higher than that of comparative examples 1-8 and positive drugs. After adding alanyl-(γ-glutamyl)-alanyl-glutamine on the basis of the above four components, it is unexpectedly found that its antidepressant activity is further improved.

[0121] Table 3: Experimental results of antidepressant activity

[0122]

[0123]

[0124] Note: *, p<0.05. **, p<0.01, compared with the vehicle group. The sample size of each group was 8, and the data were presented as mean ± standard deviation.

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

[0126] 1. Construction of anxiety disorder mouse model

[0127] The 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 open field test (OFT).

[0130] 2.1 Experimental procedures

[0131] (1) Before the experiment, animals should be adapted 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) The 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 can be 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 relevant behavioral information such as the movement distance, movement time, and number of center entries of the mice.

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

[0137] 2.2 Evaluation indicators

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

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

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

[0141] 3. Experimental results

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

[0143] In terms of exercise time: compared with the model group, tryptophan, glycine, and L-pyroglutamic acid 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, the 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 the amino acid composition 1-17 is better than 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 in the amino acid composition 1-17 increased compared with the model group, and the number of center entries was significantly greater than that in 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 m-CPP, but the activity is low, while L-alanine-cyclo (L-glutamine) and alanyl-(γ-glutamyl)-alanyl-glutamine have not been found to produce anxiolytic effects in mice. The anxiolytic effect of amino acid compositions 1-17 in different proportions is good, which 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 efficacy of the single amino acid components of tryptophan, glycine, L-pyroglutamic acid, and L-alanine-cyclo (L-glutamine) is weaker than that of the positive drug; after combining the above four components, the efficacy is significantly increased, and there is a synergistic effect relative to the activity of each single component, and its antianxiety activity is significantly higher than that of comparative examples 1-8 and positive drugs. After adding alanyl-(γ-glutamyl)-alanyl-glutamine on the basis of the above four components, surprisingly, its antianxiety activity is further improved.

[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 of 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) Preparation Formula and Preparation Method

[0154] Table 5: Preparation 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) Preparation Formula 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) Preparation Formula and Preparation Method

[0171] Table 7: Preparation 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 concentration tank, heat to boil, fill with nitrogen, and cool down.

[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 the dilution tank, pass nitrogen, adjust the pH value to 5.5-7.0 with appropriate amount of glacial acetic acid, add water for injection to the full amount, 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) Preparation Formula and Preparation Method

[0181] Table 8: Preparation 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 concentration tank, heat to boil, fill with nitrogen, and cool down.

[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 Table 2, composition 16), stir to dissolve, and adjust to volume.

[0186] (3) Filter the liquid and transfer it to the dilution tank, pass nitrogen, adjust the pH value to 5.5-7.0 with appropriate amount of glacial acetic acid, add water for injection to the full amount, 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 principle for stability test 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 relative humidity 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 the appearance, properties, active ingredient content, solubility, dispersion uniformity, clarity, pH value and sterility test of this product have no significant changes after 6 months of long-term testing, and all indicators meet the relevant provisions of the production quality standards. The product has 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 on anti-depression, antianxiety and parenteral nutrition support in 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, anti-anxiety and parenteral nutrition support for postoperative patients.

[0206] Inclusion criteria: (1) age of 18-75 years, weight 45-75 kg; (2) patients undergoing elective gastrectomy, small intestine, or colorectal resection (including laparoscopy), requiring parenteral nutrition after surgery, and with anxiety and depression; (3) nutritional screening NRS2002 score ≥ 3; Exclusion criteria: (1) patients who had received anti-anxiety or antidepressant drugs 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 1.25 g / 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 1.25 g / 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. Compare the nutritional indicators of the two groups of patients on D1, D3, and D7 after the perioperative period, including the levels of prealbumin (PA), total protein (TP), and albumin (ALB).

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

[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, obvious 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 were no significant differences 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 groups (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 control group did not change much; 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 the amino acid composition preparation D could provide nutritional support for patients after the perioperative period, and could significantly reduce the depression and anxiety levels of the patients, proving that the amino acid composition preparation D had 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 principle of the present invention should be included in the protection scope 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); 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); 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).

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

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, 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); 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 (5-15):(15-45):(0.5-1.5):(0.3-1):(0.1-1.5); 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); 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).

5. The amino acid composition according to any one of claims 1 to 4, 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; Preferably, the salt is selected from one or more of phosphate, acetate, malate, citrate, ascorbate, succinate, fumarate, and tartrate; Preferably, the amino acid composition is used in combination with other active ingredients.

6. The amino acid composition according to claim 5, characterized in that The amino acid composition further comprises a pharmaceutically acceptable excipient; Preferably, the dosage form of the amino acid composition is an enteral dosage form or a parenteral dosage form; Preferably, 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, suspensions; Preferably, the parenteral dosage form is an injection dosage form, which is selected from: injection solution, powder for injection; More preferably, the amino acid composition is in the form of tablets, capsules, or injections.

7. The amino acid composition according to claim 6, 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; Preferably, the dosage form of the amino acid composition is an injection dosage form, and the pharmaceutically acceptable excipient is water for injection and / or a pH regulator.

8. The amino acid composition according to claim 6 or 7, 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; Preferably, 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; Preferably, the amino acid composition comprises tryptophan, glycine, pyroglutamic acid, L-alanyl-cyclo (L-glutamine), water for injection, and glacial acetic acid; Preferably, 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.

9. Use of the amino acid composition according to any one of claims 1 to 8 in the preparation of a drug for preventing and / or treating depression, anxiety or insomnia; Preferably, the depression, anxiety or insomnia is caused by trauma or surgery.

10. Use of the amino acid composition according to any one of claims 1 to 8 in the preparation of a nutritional preparation.

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