Oral liquid composition of amino acids

Abstract

An oral liquid composition comprising an effective amount of an amino acid selected from L-tyrosine and L-tryptophan, a carbohydrate, water, and optionally one or more acceptable excipients, wherein the carbohydrate is at least 5% w / w in weight percentage based on the total weight of the composition, and the weight ratio of the carbohydrate to the amino acid is from 1:1 to 1:50. A method for the treatment or prevention of postpartum blues or depression using the oral liquid composition is described.

Description

Technical Field

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 390,570, filed on July 19, 2022, entitled AMINO ACID ORAL LIQUID COMPOSITION, the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to an oral liquid composition containing an amino acid selected from the group consisting of L-tryptophan and L-tyrosine, which is suitable for oral administration.

Background Art

[0003] Amino acids are essential nutrients obtained from proteins contained in foods. Among amino acids, L-tryptophan and L-tyrosine are specific in that they are precursors of neurotransmitters in the brain, and their synthesis and release are sensitive to relatively small physiological changes in precursor concentrations (Fernstrom, 1983).

[0004] L-tryptophan is an essential amino acid for humans. In addition to its role in protein synthesis, it is also involved in complex metabolic pathways that serve as precursors for the powerful neurotransmitter serotonin, the hormone melatonin, and the vitamin niacin (vitamin B3). L-tryptophan can be ingested from a wide range of high-protein foods in a normal diet, such as meat, fish, milk and dairy products, eggs, beans, lentils, bread and grains, pasta, rice, fruits, and vegetables. L-tyrosine is an essential precursor for the synthesis of the catecholamine neurotransmitters adrenaline (epinephrine), noradrenaline (norepinephrine), and dopamine, as well as the thyroid hormone thyroxine.

[0005] Fluctuations in brain L-tryptophan concentration regulate the synthesis and release of serotonin (5-hydroxytryptamine), while fluctuations in brain L-tyrosine concentration regulate the synthesis and release of catecholamine neurotransmitters (dopamine, norepinephrine, epinephrine).

[0006] Amino acid concentrations in the brain are determined by the relative concentrations of amino acids passing through the blood-brain barrier (BBB) (Pardridge et al., 1975). Amino acids compete with structurally similar amino acids for active transport across the membrane. Both tyrosine and tryptophan belong to the category of large neutral amino acids (LNAA) that includes phenylalanine, leucine, isoleucine, valine, histidine, and methionine (Belitz et al., 2009).

[0007] LNAA are taken up into the brain via transporters present in capillary endothelial cells in the depressions of the blood-brain barrier, which is both saturable and competitive. The brain concentrations of tryptophan or tyrosine are readily regulated by their uptake and the uptake of other LNAA that share a competitive transporter in their uptake from circulation into the brain. The amount of tryptophan or tyrosine actually taken up into the brain depends on the ratio of the amino acid in plasma to the total plasma concentration of LNAA.

[0008] As a result, physiological and pathophysiological factors that affect the blood concentrations of these LNAA and other LNAA that compete for the common transporter across the blood-brain barrier alter the brain aromatic amino acid concentrations, the formation and release of these monoamine neurotransmitters, and consequently brain function as predicted (Fernstrom, 1990, 1983). Treatments that affect the relative blood concentrations of L-tryptophan, L-tyrosine, and other large neutral amino acids can therefore also affect brain neurotransmitter synthesis.

[0009] Due to its role in the serotonin pathway, tyrosine and tryptophan dosage - regulating supplements are relevant to the medical treatment of various diseases such as depression, sleep disorders, cognitive disorders, anxiety disorders, or neurodegenerative diseases.

[0010] WO 2015 / 188280 (Meyer) discloses a method for treating or preventing postpartum blues in a subject in need thereof, comprising administering an antioxidant source, a tryptophan composition comprising from 2 g of L - tryptophan, and a tyrosine composition comprising from 10 g of L - tyrosine. The antioxidant source is used at least once between the first and fifth days postpartum, the tryptophan composition is administered in the evening, either simultaneously with or following the antioxidant source, between the third and fifth days postpartum, and the tyrosine composition is administered on the day following the administration of the tryptophan composition. In the examples, the antioxidant source is administered in combination with a beverage composition containing blueberry - concentrated juice and a sachet composition containing blueberry extract. Tryptophan is administered in the form of 1 g tablets, and tyrosine is administered as 0.5 mg capsules. Both the beverage composition and the sachet composition contain sugar to provide a more palatable treatment for the subject. The sugar corresponds to 9.25% w / w of the antioxidant composition. If sugar is not preferred, other sweeteners can also be used. To comply with this dosing regimen, the subject is instructed to drink concentrated blueberry juice combined with blueberry extract and to take 2 capsules of 1 g of tryptophan or 20 capsules of 0.5 mg of tyrosine each, although dosing may be accompanied by clinical supervision.

[0011] An orally - administrable liquid pharmaceutical composition is an attractive dosage form for administering a prescribed dosing regimen. Liquid pharmaceutical compositions are easy to swallow, can exhibit an attractive taste if properly formulated, and can improve patient compliance with the prescribed dosing regimen. Further, compared to solid dosage forms, liquid pharmaceutical formulations allow for more precise individualized dosing, which can be important when treating different patient populations.

[0012] Oral solutions containing L-tyrosine or L-tryptophan known in the art typically contain less than 3% w / w of carbohydrates (sugars) among their components. For example, International Publication No. WO 2004 / 047565 (Tsunoo et al.) describes an amino acid oral solution containing tyrosine, citric acid, sucrose, trehalose, and water for use as a fever reducer. The carbohydrates present in the composition are 3% w / w based on the total weight of the composition and are typically used as sweeteners or taste masking agents.

[0013] Drugs administered in the form of oral solutions can be immediately absorbed from the gastrointestinal tract and are therefore absorbed faster than the same amount of drug administered in tablets or capsules. However, to improve the uptake of L-tyrosine and L-tryptophan, particularly L-tryptophan, into the brain, it is not sufficient to simply increase the serum concentrations of both amino acids. Co-administration of L-tryptophan or L-tyrosine with other LNAAs results in a decrease in the brain concentrations of these amino acids. For further discussion regarding the relative deficiency of tryptophan or tyrosine with respect to LNAAs, see Gessa et al. 1974, Young et al. 1985, Le Masurier et al. 2006.

[0014] Despite previous efforts, there is still a need for oral liquid formulations that effectively incorporate amino acids such as L-tryptophan or L-tyrosine. SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION

[0015] The inventors of the present application have found an oral liquid composition that contains an effective amount of an amino acid selected from the group consisting of L-tryptophan and L-tyrosine, avoids problems associated with the prior art, enhances patient compliance, and at the same time maximizes the uptake of the amino acids present in the composition into the brain. MEANS FOR SOLVING THE PROBLEM

[0016] A first aspect of the present invention is - An effective amount of an amino acid selected from L-tyrosine or L-tryptophan, - At least one carbohydrate compound - Water, and - One or more acceptable excipients, An oral liquid composition comprising: Provided is an oral liquid composition wherein the composition contains more than 5% w / w of a carbohydrate compound based on the total weight of the composition, and the weight ratio of the amino acid to the carbohydrate is from 1:1 to 1:50.

[0017] Without being bound by theory, the inventors believe that, for example, if in a small amount of less than about 5% w / w, the role of the carbohydrate is as a sweetener, but above 5%, the same carbohydrate helps to promote the uptake or absorption of the amino acid incorporated into the composition by promoting the insulin response (Lee and Wolever, 1998). That is, the carbohydrate is acting as an adjuvant.

[0018] A second aspect of the present invention provides an oral liquid composition comprising an effective amount of one amino acid selected from L-tyrosine and L-tryptophan, at least one carbohydrate compound, water, and one or more pharmaceutically acceptable excipients for use in treating or preventing postpartum depression or depression in a subject in need thereof, or for use in the preparation of a medicament for treating or preventing postpartum depression or depression.

[0019] Also provided herein are methods of treating or preventing postpartum depression or depression, and corresponding uses in treatment or prevention, comprising administering to a subject in need thereof an oral liquid composition as defined in the first or second aspect of the present invention.

[0020] In a last aspect, the present invention also provides a kit comprising the oral liquid composition of the methods and uses of the present invention together with instructions for use.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] All terms used in this specification shall be construed to have their ordinary meaning as known in the relevant technical field, unless otherwise specified. More specific definitions of other particular terms used in this application are as described below, and are intended to be uniformly applied throughout this specification and the claims, unless otherwise explicitly provided with a broader definition.

[0022] In light of the objectives of the present invention, the recited ranges include both the lower and upper limits of the range.

[0023] As used herein, the term "comprising" encompasses three alternatives, namely "comprising", "consisting of", and "consisting essentially of".

[0024] As used herein, the term "oral liquid composition" refers to a physically separated unit of a liquid composition stored as a single dosage unit suitable for administration to a subject to provide a required amount of an active ingredient such as L-tyrosine or L-tryptophan. With respect to the dosage form of the present invention, the term "oral" refers to any administration method via the mouth.

[0025] As used herein, the term "postpartum depression" is defined as a transient and self-limiting condition that occurs immediately after childbirth, characterized by mood swings and mild depressive symptoms (including sadness, crying, fatigue, irritability, anxiety disorder, lack of sleep, and reduced concentration), as well as an unstable mood.

[0026] As used herein, the term "therapeutically effective amount" refers to an amount effective in the dosage and duration required to achieve one or more therapeutic results, such as a significant delay in the onset or progression of a disease, or a significant reduction in the severity of one or more symptoms. Further, a therapeutically effective amount is usually an amount where the therapeutically beneficial effect exceeds the toxic or harmful effects of the active ingredient or pharmaceutical composition.

[0027] Accordingly, an object of the present invention was to develop an oral liquid composition comprising an effective amount of an amino acid selected from the group consisting of L-tyrosine or L-tryptophan, at least one carbohydrate, water, and optionally a pharmaceutically acceptable excipient.

[0028] In one embodiment, the oral liquid composition according to the present invention comprises an effective amount of L-tyrosine. Conveniently, the oral liquid composition comprises from 1.0 g to 50.0 g of L-tyrosine, preferably from 2.0 g to 40.0 g, more preferably from 3.0 g to 30.0 g, still more preferably from 5 g to 20.0 g of L-tyrosine. In the most preferred embodiment, the oral liquid composition according to the present invention comprises 5.0 g, 6.0 g, 7.0 g, 8.0 g, 9.0 g, 10.0 g, 11.0 g, 12.0 g, 13.0 g, 14.0 g, 15.0 g, 16.0 g, 17.0 g, 18.0 g, 19.0 g or 20.0 g of L-tyrosine. In the most preferred embodiment, the oral liquid composition according to the present invention comprises 10.0 g of L-tyrosine.

[0029] In a further embodiment, the oral liquid composition of the present invention comprises an effective amount of L-tryptophan. Conveniently, the oral liquid composition comprises from 0.5 g to 20.0 g of L-tryptophan, more preferably from 1 to 10 g, still more preferably from 1 to 5 g of L-tryptophan. In the most preferred embodiment, the composition according to the present invention comprises 2 g of L-tryptophan.

[0030] In some specific embodiments of the present invention, in order to prevent partial deficiency of the uptake of tryptophan or tyrosine from the composition of the present invention into the brain, the oral liquid composition of the present invention is substantially free of other amino acids selected from phenylalanine, leucine, isoleucine, valine, histidine and methionine.

[0031] In the context of the present invention, "substantially free of" means that the composition contains an amount of said amino acid of less than 2% w / w, in particular less than 1% w / w, in particular less than 0.5% w / w.

[0032] In some embodiments, the oral liquid composition according to the present invention contains L-tyrosine at about 2 mg / mL to 100 mg / mL, preferably 3 mg / mL to 85 mg / mL, more preferably 5 mg / mL to 75 mg / mL, and even more preferably 6 mg / mL to 65 mg / mL. In the most preferred embodiment, the oral liquid composition according to the present invention contains L-tyrosine at 45 mg / mL to 55 mg / mL.

[0033] In a further embodiment, the oral liquid composition according to the present invention contains L-tryptophan at 2.5 mg / mL to 100 mg / mL, preferably 3 mg / mL to 85 mg / mL, more preferably 5 mg / mL to 75 mg / mL, and even more preferably 6 mg / mL to 65 mg / mL. In the most preferred embodiment, the oral liquid composition according to the present invention contains L-tryptophan at 8 mg / mL to 12 mg / mL.

[0034] In one embodiment, the oral liquid composition according to the present invention contains carbohydrates in an amount of about 5% to about 50% w / w, or about 10% to about 40% w / w, or about 15% to about 30% w / w of the total weight of the composition. In some embodiments, the formulation contains at least one carbohydrate in an amount of 20% to about 25% w / w of the total weight of the composition. In a preferred embodiment, the carbohydrate is present in the formulation in an amount greater than 5% w / w of the total weight of the composition, more preferably greater than 10% w / w of the total weight of the composition, and even more preferably greater than 15% w / w of the total amount of the composition.

[0035] In a further embodiment, the oral liquid composition according to the present invention contains 50 to 60 g of carbohydrates, preferably 53 to 57 g of carbohydrates, provided that the carbohydrates are in the range of 5% to 30% w / w based on the total weight of the composition.

[0036] In some embodiments, the carbohydrate is a simple carbohydrate (sugar) or saccharide. In preferred embodiments, the saccharide is one or more of glucose, galactose, fructose, xylose, sucrose, lactose, maltose, mannose, trehalose, sorbitol, mannitol, xylitol, raffinose, cellobiose, inulin, maltopolysaccharides, starch, and cellulose, or a combination thereof. Preferred saccharides are selected from sucrose, fructose, and mixtures thereof.

[0037] In one embodiment, the oral liquid composition according to the present invention comprises a carbohydrate selected from sucrose, fructose, or mixtures thereof at a concentration of about 5% to about 50% w / w, or about 10% to about 40% w / w, or about 15% to about 30% w / w of the total weight of the composition. In some embodiments, the formulation comprises at least one carbohydrate selected from sucrose, fructose, or mixtures thereof at a concentration of 20% to about 25% w / w of the total weight of the composition. In preferred embodiments, the carbohydrate is selected from sucrose, fructose, or mixtures thereof and is present in the formulation at a concentration higher than 5% w / w of the total weight of the composition, for example higher than 10% w / w of the total weight of the composition, for example higher than 15% w / w of the total amount of the composition.

[0038] In some embodiments, the weight ratio of amino acid to carbohydrate is from 1:1 to 1:50. In preferred embodiments, the weight ratio of amino acid to carbohydrate is from 1:2 to 1:40, more preferably from 1:3 to 1:30. In the most preferred embodiment, the weight ratio of amino acid to carbohydrate is from 1:5 to 1:26.

[0039] In one embodiment, the composition comprises L-tryptophan and its weight ratio is 1:10 to 1:40, 1:20 to 1:35, or 1:25 to 1:30 with respect to the carbohydrate.

[0040] In an alternative embodiment, the composition comprises L-tyrosine and its weight ratio is 1:2 to 1:30, 1:3 to 1:15, 1:4 to 1:10 with respect to the carbohydrate.

[0041] In the present invention, the "weight ratio of amino acid:carbohydrate" is defined as the ratio of the amount of amino acid to the amount of carbohydrate, and both amounts are expressed in the same unit (gram or milligram).

[0042] The oral liquid composition according to the present invention contains water as a solvent. In some embodiments, water is present in an amount of 50% to about 95% w / w, or about 60% to about 85% w / w, or about 65% to about 80% w / w of the total weight of the composition. In a preferred embodiment, the oral liquid composition according to the present invention contains about 68% to about 78% w / w of the total weight of the composition. In the most preferred embodiment, the oral liquid composition according to the present invention contains about 72% to about 78% w / w of the total weight of the composition.

[0043] In a preferred embodiment, the liquid composition according to the present invention contains at least one component having antioxidant ability.

[0044] As used herein, the term "antioxidant" refers to the ability of a substance contained in an antioxidant composition or may include a precursor compound that is converted into an antioxidant substance in the body when ingested.

[0045] The component having antioxidant ability according to the present invention may be of natural origin, preferably obtained from plants. Such components may be plant extracts or plant powders. The plants referred to here include all parts of the plant such as fruits such as leaf skin, seeds or berries.

[0046] Preferred components derived from plants having antioxidant ability are selected from the group comprising polyphenols, especially flavonoids, ellagitannins, xanthones, tannins and anthocyanins and other plant polyphenols. In the most preferred embodiment, the component having antioxidant ability and / or antioxidant enzyme induction ability is anthocyanin. Anthocyanin may be separated from blueberries or may be administered as a blueberry extract.

[0047] In some embodiments, the antioxidant component may be selected from vitamin C, vitamin E, indole-3-carbinol, glutathione, or a mixture thereof.

[0048] In one embodiment, the composition is a food supplement. As used herein, the term "food supplement", also referred to as "nutritional supplement", refers to a concentrated source of nutrients or other substances having nutritional or physiological effects, which is intended to supplement a normal diet. In other words, a food supplement is a concentrated source of vitamins or minerals or other substances having nutritional or physiological effects, which is intended to supplement a normal diet, and means any food used alone or in combination. Food supplements are preferably sold in dosage forms. The definition of "supplement" may be interpreted as being taken in addition to a diet.

[0049] In other embodiments, the composition is a pharmaceutical composition or a nutraceutical composition.

[0050] The oral liquid composition may optionally contain at least one taste masking agent or bitterness blocking agent. Taste masking agents include sweeteners and flavoring agents, which may be used alone or in combination.

[0051] In addition to sweeteners, the liquid pharmaceutical composition or nutraceutical composition may contain a flavoring agent. Useful flavoring agents include various fruit flavors (e.g., orange, cherry, strawberry, grape, blueberry, etc.), mint, cocoa, chocolate, and vanilla flavor.

[0052] An oral liquid pharmaceutical composition or a nutritional supplement composition may optionally contain a viscosity modifier for increasing the viscosity of the composition. By increasing the viscosity, it is considered that the handling of the composition is improved and the taste of the pharmaceutical composition or the nutritional supplement formulation is improved. Useful viscosity modifiers include hydroxyethyl cellulose, xanthan gum, guar gum, etc., and these may be used alone or in combination. A preferred viscosity modifier according to the present invention is guar gum.

[0053] The viscosity modifier may be used at a concentration of at least about 0.001 mg / mL or more and about 5 mg / mL or less.

[0054] Also provided herein are methods of treating or preventing postpartum depression or depression, and corresponding uses in treatment or prevention / protection, including administering to a subject in need thereof an oral liquid composition as defined in any of the above aspects and embodiments.

[0055] As used herein, "treatment" refers to dealing with postpartum depression or depressive mood and its precursors in an individual who already exhibits symptoms and precursors of postpartum depression or depressive mood during the puerperium, in a way that improves them. Improvement of postpartum depression or sad mood may be equivalently described in this specification as improvement of postpartum depression or depressive mood. Treatment does not have to completely cure or eradicate an individual's depressive or depressive mood, but may simply alleviate the intensity or duration of one or more symptoms such as non-functional attitudes, crying, irritability, decreased concentration, changes in appetite, fatigue, depression, anxiety disorder, changes in calmness or tension, restlessness, confusion, anger, and / or fatigue. Improvement of mood may be determined by the individual, by a medical professional, or by using acceptable parameters such as surveys, questionnaires, physiological tests, etc. It is considered treatment to improve symptoms without completely eradicating postpartum depression or depressive mood. Treatment may be a reduction in the severity or duration of symptoms determined by self-report, or a reduction in clinically acceptable parameters used to evaluate postpartum depression or depressive mood, including questionnaire surveys or behavioral assessment techniques.

[0056] As used herein, "prevention" or "prevention" of depressive mood occurring during the puerperium means dealing with it before the occurrence of depressive mood in a way that completely or partially prevents, delays, or reduces its occurrence. Also included in prevention and prevention is dealing with it before the occurrence or exacerbation of depressive mood so as to reduce the severity, duration, and likelihood of recurrence of depressive mood and its symptoms, and as a result, improve the individual. "Prevention" and "prevention" do not mean that depressive mood does not occur in that individual, but rather mean taking measures before the occurrence of depressive mood to deal with the problem. Taking preventive or preventive measures before occurrence is beneficial to the individual, and this can be utilized proactively even if depressive mood is only partially prevented. Methods and compositions for dealing with depressive mood are described in International Publication No. WO 2015 / 1188280 (Meyer).

[0057] In one embodiment, the oral liquid composition of the present invention is administered to the subject from the third day to the fifth day after childbirth.

[0058] In other embodiments, the oral liquid composition of the present invention is administered once, twice or three times a day. In other embodiments, the oral liquid composition of the present invention is administered once a day.

[0059] In other embodiments, the method comprises administering an oral liquid composition of the invention comprising an effective amount of L - tyrosine that is effective in avoiding or alleviating symptoms and / or therapeutically effective. In an alternative embodiment, the method comprises administering an oral liquid composition of the invention comprising an amount of L - tryptophan effective in avoiding or reducing symptoms and / or therapeutically effective. In an alternative embodiment, the method comprises administering, either simultaneously, sequentially, or separately, an oral liquid composition of the invention comprising a therapeutically effective amount of L - tyrosine and an oral liquid composition of the invention comprising a therapeutically effective amount of L - tryptophan. In an alternative embodiment, the method comprises sequentially administering an oral liquid composition of the invention comprising a therapeutically effective amount of L - tyrosine and an oral liquid composition of the invention comprising a therapeutically effective amount of L - tryptophan. In an alternative embodiment, the method comprises administering an oral liquid composition of the invention comprising a therapeutically effective amount of L - tyrosine and an oral liquid composition of the invention comprising a therapeutically effective amount of L - tryptophan, sequentially and on different days. In an alternative embodiment, the method comprises first administering an oral liquid composition of the invention comprising a therapeutically effective amount of L - tryptophan, followed by administering an oral liquid composition of the invention comprising a therapeutically effective amount of L - tyrosine. In an alternative embodiment, the method comprises first administering, sequentially and on different days, an oral liquid composition of the invention comprising a therapeutically effective amount of L - tryptophan, followed by an oral liquid composition of the invention comprising a therapeutically effective amount of L - tyrosine. In an alternative embodiment, the method comprises first administering an oral liquid composition of the invention comprising a therapeutically effective amount of L - tryptophan and then administering an oral liquid composition of the invention comprising a therapeutically effective amount of L - tyrosine the next day. In an alternative embodiment, the L - tryptophan and L - tyrosine solutions are administered between the first and fifth days after childbirth. In an alternative embodiment, the L - tryptophan solution is first administered, followed by the L - tyrosine solution, between the first and fifth days after childbirth. In an alternative embodiment, the L - tryptophan solution is first administered, and then on a different day, the L - tyrosine solution is administered between the first and fifth days after childbirth.

[0060] In an alternative possible embodiment, first, the tryptophan composition is administered on the fourth day after childbirth, and the tyrosine oral liquid composition is administered on the fifth day after childbirth.

[0061] The method of the present invention may include the administration of at least one antioxidant composition in a liquid or solid form that is substantially free of amino acids. In one embodiment, the additional antioxidant composition is administered separately. In one embodiment, the other antioxidant composition, in either solid or liquid form, is administered before the tryptophan composition. In other embodiments, the other antioxidant composition, in either liquid or solid form, is administered on the third day after childbirth. In other embodiments, an antioxidant composition in either liquid or solid form is administered on the third and fourth days after childbirth, the tryptophan composition is administered on the fourth day after childbirth, and the tyrosine composition is administered on the fifth day after childbirth.

[0062] According to a further aspect, the oral liquid composition according to the present invention can be used as part of a multi-component kit. The kit is suitable for use in the treatment or prevention of postpartum depression or depression, a. An oral liquid composition comprising an effective amount of L-tryptophan, at least one carbohydrate compound that is at least 5% w / w by weight (wherein the weight ratio of the amino acid to the carbohydrate is from 1:1 to 1:50), water, and optionally a pharmaceutically acceptable excipient; b. An oral liquid composition comprising an effective amount of L-tyrosine, at least one carbohydrate compound that is at least 5% w / w by weight (wherein the weight ratio of the amino acid to the carbohydrate is from 1:1 to 1:50), water, and optionally a pharmaceutically acceptable excipient; and For example, instructions for the administration of both compositions for administration on the fourth to fifth days after childbirth, are included.

[0063] Generally, the kit further comprises an oral liquid beverage comprising at least one carbohydrate compound, water, at least one component having antioxidant ability, and optionally one or more acceptable excipients, and is administered on the 1st to 3rd day after childbirth.

[0064] In a preferred embodiment, the kit a. An oral liquid composition comprising an effective amount of L-tryptophan, at least one carbohydrate compound that is at least 5% w / w by weight (wherein the weight ratio of the amino acid to the carbohydrate is 1:1 to 1:50), water, at least one component having antioxidant ability, and optionally one or more acceptable excipients; b. An oral liquid composition comprising an effective amount of L-tyrosine, at least one carbohydrate compound that is at least 5% w / w by weight (wherein the weight ratio of the amino acid to the carbohydrate is 1:1 to 1:50), water, at least one component having antioxidant ability, and optionally one or more acceptable excipients; c. An oral composition in either liquid or solid form, comprising at least one carbohydrate compound, water, at least one component having antioxidant ability, and optionally one or more acceptable excipients, but substantially free of amino acids; and For example, instructions for administration for administration between the 1st and 5th day after childbirth, are included.

[0065] The oral solid composition containing the antioxidant component can take the form of, for example, tablets, tablets, powders or capsules of any antioxidant suitable in the context of the present invention (see above). There are well-known commercially available antioxidant solid compositions.

[0066] The kit of the present invention provides instructions for administration of the oral liquid composition of the present invention provided in one of the above embodiments related to the administration of the formulation (separately, sequentially, simultaneously; on separate or the same day; in the case of postpartum depression, a specific dosing regimen, etc.). Therefore, the above embodiments provided under the methods of treatment and prevention are the same in the embodiments when using the kit of the present invention.

[0067] According to a further aspect, the kit includes a plurality of liquid compositions together with instructions for oral administration in a multi-day postpartum regimen for the treatment or prevention of postpartum depression or depression in a subject in need thereof.

[0068] The plurality of liquid compositions are a first composition and a second composition comprising 50 - 60 g of carbohydrates and an antioxidant source, wherein the carbohydrates are 5% - 30% w / w based on the total liquid weight of the composition, and the first composition and the second composition are essentially free of amino acids and may be the same as or different from each other; a third composition comprising 50 - 60 g of carbohydrates, an antioxidant source, and an amino acid comprising L-tryptophan, wherein the weight ratio of L-tryptophan to carbohydrates is 1:10 - 1:40 and the carbohydrates are 5% - 30% w / w based on the total liquid weight of the composition; and a fourth composition comprising 50 - 60 g of carbohydrates, an antioxidant source, and an amino acid comprising L-tyrosine, wherein the weight ratio of L-tyrosine to carbohydrates is 1:2 - 1:30 and the carbohydrates are 5% - 30% w / w based on the total liquid weight of the composition; and instructions for oral administration in a multi-day postpartum regimen for the treatment or prevention of postpartum depression or depressive mood in a subject in need thereof, and

[0069] For example, the instructions for use may instruct administration of the first composition in the evening of the first day of the postpartum regimen; the second composition in the morning of the second day of the postpartum regimen; the third composition in the evening of the second day of the postpartum regimen; and the fourth composition in the morning of the third day of the postpartum regimen.

[0070] For example, the third composition may include L-tryptophan in a weight ratio to carbohydrates of 1:20 - 1:35 or 1:25 - 1:30; and the fourth composition may include L-tyrosine in a weight ratio to carbohydrates of 1:3 - 1:15 or 1:4 - 1:10.

[0071] The kit may also have one or more of the following features: the first day of the regime may correspond to the third day after the subject's childbirth; the antioxidant source may include blueberry extract and / or blueberry juice; the carbohydrate may be 20% - 30% w / w of the total weight of the composition; the third composition may include 1 - 5 g of L-tryptophan, for example, 2 g of L-tryptophan; the fourth composition may include 5 - 20 g of L-tyrosine, for example, 10 g of L-tyrosine; one or more of the compositions may be provided in the form of a shake; the carbohydrate may include simple carbohydrates, such as sucrose; the antioxidant source may include blueberry extract and / or juice that provides 6500 ORAC units / g; and / or the composition may further include excipients or vehicles selected from the group consisting of taste masking agents, bitterness blockers, sweeteners, flavors, viscosity modifiers, thickeners, guar gum, dietary fiber, cocoa powder, and combinations thereof.

[0072] The following examples are intended to be illustrative and non-limiting and represent specific embodiments of the present invention.

Example

[0073] Example 1 Oral Solution of L-Tryptophan The following oral solution, outlined in Table 1, is an example of an oral amino acid solution in which the amino acid L-tryptophan is present in a ratio of approximately 2 g:55.84 g (or approximately 1:27.92) relative to the carbohydrate (mainly sucrose). Further, the carbohydrate from sucrose is 21.38% when expressed as a weight percentage of the total weight of the composition. The single dose represented in Table 1 is 261.274 g and involves ingesting 55.84 g of sugar at once per dose, and thus has a high sugar content to assist in the absorption and uptake of the amino acid component. This example of the oral solution includes excipients, and the blueberry extract imparts antioxidant ability to the solution. This solution may be supplied in the form of a prepared solution that can be shaken to enhance mixing and palatability.

[0074]

Table 1

[0075] Example 2 Oral solution of L - tyrosine The oral solution in Table 2 below is an example of an oral amino acid solution in which the amino acid L - tyrosine is present in a ratio of approximately 10.204 g:55.84 g (or approximately 1:5.45) with respect to the carbohydrate (mainly sucrose). Further, the carbohydrate derived from sucrose is 20.78% when expressed as a weight percentage of the total weight of the composition. The single dose represented in Table 2 is 268.678 g and it is for ingesting 55.84 g of sugar at a time per dose, and thus has a high sugar content to assist in the absorption and uptake of the amino acid component. This exemplary oral solution contains excipients, and the blueberry extract imparts antioxidant ability to the solution. This solution may be supplied in the form of a prepared solution that can be shaken to enhance mixing and palatability.

[0076]

Table 2

[0077] Example 3 (Reference Example) Beverage containing antioxidant The following oral solution outlined in Table 3 is a reference example of an oral amino acid solution that does not contain amino acids. The carbohydrate present (mainly sucrose) is approximately 55.84 g. The carbohydrate derived from sucrose is 21.35% when expressed as a weight percentage of the total weight of the composition. The single dose represented in Table 3 is 261.474 g and it is ingested at once as a single portion. This exemplary oral solution contains excipients, and the blueberry extract imparts antioxidant ability to the solution. This solution can be supplied in the form of a prepared solution that can be shaken to enhance miscibility and palatability.

[0078]

Table 3

[0079] Example 4 Composition for the subject after childbirth To complete this trial, pregnant women without a history of major depressive episode (MDE) and in good health are recruited during the third trimester of pregnancy. The subjects are randomly assigned to placebo or active supplement within blocks of 2, 4, 6, 8, or 10 by double-blind method. The supplement / placebo is taken at four time points from the night of the third day postpartum to the morning of the fifth day postpartum (see the schedule below). The subjects are administered either a liquid formulation or a placebo with the same taste and color.

[0080] Administration Timing of Test Formulation - Night of the third day postpartum: The participant drinks the antioxidant liquid composition or placebo liquid composition disclosed in Example 3. - Morning of the fourth day postpartum: The participant drinks the antioxidant liquid composition or placebo liquid composition disclosed in Example 3. - Night of the fourth day postpartum: The participant drinks the tryptophan liquid composition or placebo liquid composition disclosed in Example 1. - Morning of the fifth day postpartum: The participant drinks the tyrosine liquid composition or placebo liquid composition disclosed in Example 2.

[0081] On the fifth day, after administration of the liquid composition, the participants are requested to complete the following means: - Pittsburgh Sleep Quality Index. This questionnaire is used to evaluate the sleep quality of the subject. - First, the subject undergoes a neutral mood induction procedure (MIP) based on Velten. This is the most widely used technique for studying the affective impact on behavior and has been demonstrated to be effective in changing subjective emotional states (Frost et al., 1982) After the neutral MIP, the subject fills in the following questionnaire in a predetermined order: a. The Visual Analog Scale (VAS) is such that each of the eight items is indicated by the participant on a scale of 0 to 10 as to how well it matches how they are feeling at that time. The items include depression, happiness, restlessness, sadness, anxiety, anger, drowsiness, and vigilance. Among the VAS, the mood is first evaluated. b. The Dysfunctional Attitude Scale (DAS) is developed to identify and measure cognitive distortions, especially those that may be related to or cause depression. c. The Profile of Mood State (POMS) evaluates 65 adjectives on a five-point scale. Six factors are obtained, including tension, depression, anger, fatigue, vigor, and confusion. d. VAS e. The State-Trait Anxiety Inventory consists of two scales, each containing 20 items. One scale corresponds to state anxiety, and the other scale corresponds to trait anxiety. The total score indicates which type of anxiety is dominant and distinguishes the person's state and trait anxiety levels. - Next, the subject undergoes an induction into a sad mood based on the Velten MIP. Following the Sadness MIP, the subject repeats the above questionnaire in a predetermined order. - After the above questionnaire, the subject undergoes an Affective Stroop Test. This test is used as an information processing approach to evaluate emotions. The Affective Stroop Test functions by examining the reaction time when the subject names the color of negative emotion words. - VAS - The subject undergoes an induction into a neutral mood. - VAS - The Beck Depression Inventory (BDI), a standardized health questionnaire - The Edinburgh Postnatal Depression Scale (EPDS), a standardized health survey. - The Stein-Bruce Scale is a self-assessment scale consisting of 13 symptoms (depression, crying, anxiety disorder, tension, restlessness, fatigue, dreaming, appetite, headache, irritability, decreased concentration, forgetfulness, confusion). - Kennerley and Gath is a self-assessment 28-item questionnaire for depression. - HAM-D, a standard health questionnaire - The Center for Epidemiological Studies Depression Scale (CES-D) 165 is a 20-item depression scale ranging from 0 (least depressed) to 60 (most depressed). - Safety and tolerance checklist - Records of the meals on the night of the fourth day after childbirth and the morning of the fifth day after childbirth

[0082] The primary analysis uses repeated measures analysis of variance with the visual analog scale of depressive mood as the repeated scale (before and after the sad MIP), and the active condition versus placebo as the between-subjects scale.

[0083] The secondary analysis was performed on the change in the depressive mood score of the Profile of Mood State (POMS) scale using repeated measures analysis of variance with the POMS score as the repeated scale (before and after the sad MIP) and the active condition versus placebo as the between-subjects scale.

[0084] The methods and timing of evaluation, recording, and analysis of safety parameters are as follows. Adverse events are recorded in the Adverse Event Log. The Principal Investigator makes a judgment regarding the reasonable causal relationship with the investigational drug and the severity of the adverse event through consultation. Adverse events are recorded until the end of the test on the fifth day after childbirth.

[0085] Example 5 A shake prepared for the treatment or prevention of postpartum depression or depressive illness A kit containing a single dose of multiple liquids is packaged together for use by postpartum people who have experienced postpartum depression or depressive mood or wish to avoid it preventively over a multi - day regimen.

[0086] The kit comes with, for example, four sealed containers, each sealed container labeled with the time of day to be taken over a multi - day regimen, such as the morning or evening of the first day of the regimen (corresponding to the third day postpartum), the second day (corresponding to the fourth day postpartum), or the third day (corresponding to the fifth day postpartum). The convenience of the prepared liquid format in a sealed container allows the user to refrigerate and shake the container well before use, thereby dissolving stabilizers such as thickeners and other excipients to obtain a thick and consistent mouthfeel. During the often hectic and confusing postpartum period, the convenience of a product that can be taken as scheduled facilitates the adaptation of new parents to various situations and eases compliance with taking the medication. Clear labeling of each container and an easy - to - understand instruction manual for the kit also promote compliance with taking the medication.

[0087] The sugar content of each individual container (representing a single dose) may be in the range of 40 - 65, for example 55 - 58 g per single dose. The tyrosine or tryptophan content per single dose may be, for example, 2 g of L - tryptophan (as in Example 1, Table 1) or 10 g of L - tyrosine (as in Example 2, Table 2). Each container may be of a size unified with the other containers of the kit, as long as it is a dose that an individual can take at one time, and may be in the range of 250 - 300 mL.

[0088] Thickeners and other ingredients to create a desirable mouthfeel represented by "shake" make the formulation more desirable for the subject.

[0089] By preparing the formulation in a convenient format that ensures it is refreshing, delicious, fruity, and healthy while being easily packaged in kit form afterwards, compliance with the target's medication can be promoted. For example, four clearly labeled bottles can be sold in a box along with an easy-to-understand instruction manual, which can be optionally refrigerated and shaken before use. The instruction manual may follow, for example, the regimen described by Meyer (2015) in WO 2015 / 188280.

[0090] Exemplary regimens may be as follows.

[0091] [Table 4]

[0092] Reference The following documents are hereby incorporated by reference into this specification. [Table 5]

[0093] Clauses For the sake of completeness, various aspects of the present invention are presented in the following numbered clauses.

[0094] Section 1. An oral liquid composition comprising an effective amount of an amino acid selected from L-tyrosine and L-tryptophan, a carbohydrate, water, and optionally one or more acceptable excipients, wherein the carbohydrate is at least 5% w / w by weight based on the total weight of the composition, and the weight ratio of the amino acid to the carbohydrate is from 1:1 to 1:50.

[0095] Section 2. The amino acid is L-tyrosine, and the carbohydrate is in excess by weight relative to the amino acid. In particular, the weight ratio of the L-tyrosine to the carbohydrate is from 1:2 to 1:30, from 1:3 to 1:15, or from 1:4 to 10, or alternatively The amino acid is L-tryptophan, and the carbohydrate is in excess of the amino acid by weight ratio. In particular, the weight ratio of the L-tryptophan to the carbohydrate is 1:10 to 1:40, 1:20 to 1:35, or 1:25 to 1:30. The oral liquid composition according to Section 1.

[0096] Section 3. The oral liquid composition according to Section 1 or Section 2, wherein the carbohydrate is present in the composition at a w / w% of about 5% to about 50% w / w, or about 10% to about 40% w / w, or about 15% to about 30% w / w of the total weight of the composition.

[0097] Section 4. The oral liquid composition according to any one of Sections 1 to 3, wherein the oral liquid composition contains 5 g to 20.0 g of L-tyrosine, particularly 10 g of L-tyrosine.

[0098] Section 5. The oral liquid composition according to any one of Sections 1 to 4, wherein the oral liquid composition contains 1 g to 10 g of L-tryptophan, particularly 2 g of L-tryptophan.

[0099] Section 6. The oral liquid composition according to any one of Sections 1 to 5, wherein the composition contains L-tyrosine or L-tryptophan at 3 mg / mL to 75 mg / mL.

[0100] Section 7. The oral liquid composition according to any one of Sections 1 to 6, further comprising at least one component having antioxidant ability.

[0101] Section 8. The oral liquid composition according to Section 7, wherein the component having antioxidant ability is selected from the group consisting of flavonoids, ellagitannins, xanthones, tannins, anthocyanins, vitamin C, vitamin E, indole-3-carbinol, glutathione, and mixtures thereof.

[0102] Section 9. An oral liquid composition according to any one of Sections 1 to 8, wherein the composition substantially does not contain other amino acids selected from phenylalanine, leucine, isoleucine, valine, histidine, and methionine.

[0103] Section 10. An oral liquid composition according to any one of claims 1 to 9, wherein the composition contains one or more suitable excipients or vehicles selected from taste masking agents, bitterness blocking agents, sweeteners, flavoring agents, and viscosity modifiers.

[0104] Section 11. A composition according to any one of Sections 1 to 10, which is a food supplement and contains excipients acceptable for food use.

[0105] Section 12. A composition according to any one of Sections 1 to 10, which is a pharmaceutical composition and contains pharmaceutically acceptable excipients.

[0106] Section 13. a. An oral liquid composition according to any one of Sections 1 to 12, wherein the amino acid is L-tryptophan; b. An oral liquid composition according to any one of Sections 1 to 12, wherein the amino acid is L-tyrosine; and instructions regarding the administration of both compositions, comprising a kit.

[0107] Section 14. a. An oral liquid composition as defined in any one of Sections 1 to 12, wherein the amino acid is L-tryptophan; b. An oral liquid composition as defined in any one of Sections 1 to 12, wherein the amino acid is L-tyrosine; c. A liquid or solid oral composition comprising at least one carbohydrate compound, water, at least one component having antioxidant capacity, and optionally one or more acceptable excipients, wherein the oral liquid solution substantially does not contain amino acids; and instructions for administration comprising the kit according to Section 13.

[0108] Section 15. A method for the treatment or prevention of postpartum depression or depression in a subject in need thereof, said method comprising administering an oral liquid composition as defined in any one of Sections 1 to 12, said composition comprising a therapeutically effective amount of one amino acid selected from L-tyrosine and L-tryptophan, at least one carbohydrate compound, water, and a pharmaceutically acceptable excipient, or alternatively, comprising using a kit as defined in Section 13 or 14.

[0109] Section 16. The method according to Section 15, wherein said tryptophan oral liquid composition and said tyrosine oral liquid formulation are not administered on the same day.

[0110] Section 17. The method according to Section 15 or 16, wherein said tryptophan oral liquid composition is administered on the fourth day postpartum and said tyrosine oral liquid composition is administered on the fifth day postpartum.

[0111] Section 18. The method according to any one of Sections 15 to 17, further comprising administering an oral liquid composition comprising an antioxidant compound as defined above.

[0112] Section 19. The method according to Section 18, wherein said further antioxidant compound is administered on the third day postpartum.

[0113] Section 20. The method according to Section 19, wherein said further antioxidant compound is further administered on the fourth day postpartum.

[0114] Section 21. A kit comprising a plurality of liquid compositions together with instructions for oral administration in a postpartum regimen for the treatment or prevention of postpartum depression or depressive mood in a subject in need thereof, wherein said plurality of liquid compositions comprises A first composition and a second composition comprising 50 to 60 g of carbohydrates and an antioxidant source, wherein the carbohydrates are 5% to 30% w / w based on the total liquid weight of the composition, and the first composition and the second composition are essentially free of amino acids and may be the same as or different from each other, the first composition and the second composition; A third composition comprising 50 to 60 g of carbohydrates, an antioxidant source, and an amino acid consisting of L-tryptophan, wherein the weight ratio of the L-tryptophan to the carbohydrates is 1:10 to 1:40, and the carbohydrates are 5% to 30% w / w based on the total liquid weight of the composition, the third composition; and A fourth composition comprising 50 to 60 g of carbohydrates, an antioxidant source, and an amino acid consisting of L-tyrosine, wherein the weight ratio of the L-tyrosine to the carbohydrates is 1:2 to 1:30, and the carbohydrates are 5% to 30% w / w based on the total liquid weight of the composition, the fourth composition comprising; The following dosing instructions: The first composition in the evening on the first day of the postnatal regimen; The second composition in the morning on the second day of the postnatal regimen; The third composition in the evening on the second day of the postnatal regimen; and The fourth composition in the morning on the third day of the postnatal regimen A kit comprising.

[0115] Section 22. The third composition comprises the L-tryptophan and the carbohydrates in a weight ratio of 1:20 to 1:35 or 1:25 to 1:30; and The fourth composition comprises the L-tyrosine and the carbohydrates in a weight ratio of 1:3 to 1:15 or 1:4 to 1:10, The kit according to Section 21.

[0116] Section 23. The first day of the regimen corresponds to the third day after the subject's delivery; The antioxidant source comprises blueberry extract and / or blueberry juice; The antioxidant source comprises blueberry extract and / or blueberry juice; The carbohydrate is 20% to 30% w / w of the total weight of the composition; The third composition contains 1 to 5 g of L-tryptophan, or 2 g of L-tryptophan; One or more of the compositions are provided in the form of a shake; The carbohydrate contains simple carbohydrates or sucrose; The fourth composition contains 5 to 20 g of L-tyrosine, or 10 g of L-tyrosine; The antioxidant source includes blueberry extract and / or fruit juice that provides 6500 ORAC units / g; and / or The composition further comprises one or more excipients or vehicles selected from the group consisting of a taste masking agent, a bitterness blocker, a sweetener, a flavor, a viscosity modifier, a thickener, guar gum, dietary fiber, and / or cocoa powder The kit according to section 21 or section 22.

Claims

1. An oral liquid composition comprising an effective amount of an amino acid selected from L - tyrosine and L - tryptophan, a carbohydrate, water, and optionally one or more acceptable excipients, wherein the carbohydrate is at least 5% w / w by weight relative to the total weight of the composition, and the weight ratio of the amino acid to the carbohydrate is from 1:1 to 1:

50.

2. The amino acid is L - tyrosine, and the carbohydrate exceeds the amino acid in weight ratio. In particular, the weight ratio of the L - tyrosine to the carbohydrate is from 1:2 to 1:30, from 1:3 to 1:15, or from 1:4 to 1:10, or alternatively The amino acid is L - tryptophan, and the carbohydrate exceeds the amino acid in weight ratio. In particular, the weight ratio of the L - tryptophan to the carbohydrate is from 1:10 to 1:40, from 1:20 to 1:35, or from 1:25 to 1:

30. The oral liquid composition according to claim 1.

3. The oral liquid composition according to claim 1, wherein the carbohydrate is about 5% - about 50% w / w, or about 10% - about 40% w / w, or about 15% - about 30% w / w by weight of the total weight of the composition.

4. The oral liquid composition according to claim 1, wherein the composition contains L - tyrosine or L - tryptophan at 3 mg / mL to 75 mg / mL.

5. The oral liquid composition according to claim 1, further comprising at least one component having antioxidant ability.

6. The oral liquid composition according to claim 1, wherein the composition is substantially free of other amino acids selected from phenylalanine, leucine, isoleucine, valine, histidine, and methionine.

7. The oral liquid composition according to claim 1, wherein the composition contains one or more suitable excipients or vehicles selected from taste - masking agents, bitterness - blocking agents, sweeteners, flavoring agents, and viscosity - modifying agents.

8. The composition according to claim 1, which is a food supplement.

9. The composition according to claim 1, which is a pharmaceutical composition and contains pharmaceutically acceptable excipients.

10. a. An oral liquid composition comprising an effective amount of L - tryptophan, at least one carbohydrate compound at least 5% w / w by weight (the weight ratio of the amino acid to the carbohydrate is from 1:1 to 1:50), water, and optionally pharmaceutically acceptable excipients; b. An oral liquid composition comprising an effective amount of L - tyrosine, at least one carbohydrate compound in an amount of at least 5% w / w by weight (the weight ratio of amino acid to carbohydrate being from 1:1 to 1:50), water, and optionally a pharmaceutically acceptable excipient; and Instructions for administration of both compositions A kit comprising the same.

11. a. An oral liquid composition comprising an effective amount of L - tryptophan, at least one carbohydrate compound in an amount of at least 5% w / w by weight (the weight ratio of amino acid to carbohydrate being from 1:1 to 1:50), water, at least one component having antioxidant ability, and optionally one or more acceptable excipients; b. An oral liquid composition comprising an effective amount of L - tyrosine, at least one carbohydrate compound in an amount of at least 5% w / w by weight (the weight ratio of amino acid to carbohydrate being from 1:1 to 1:50), water, at least one component having antioxidant ability, and optionally one or more acceptable excipients; c. An oral composition, liquid or solid, comprising at least one carbohydrate compound, water, at least one component having antioxidant ability, and optionally one or more acceptable excipients, wherein the antioxidant composition is substantially free of amino acids; and Instructions for administration A kit comprising the same.

12. The oral liquid composition according to claim 5 or the kit according to claim 11, wherein the component having antioxidant ability is selected from the group consisting of flavonoids, ellagitannins, xanthones, tannins, anthocyanins, vitamin C, vitamin E, indole - 3 - carbinol, glutathione, and mixtures thereof.

13. A method for the treatment or prevention of postpartum depression or depression in a subject in need thereof, the method comprising administering an oral liquid composition according to claim 1, which composition comprises a therapeutically effective amount of one amino acid selected from L - tyrosine and L - tryptophan, at least one carbohydrate compound, water, and a pharmaceutically acceptable excipient, or alternatively, comprising using the kit according to claim 10 or claim 11.

14. The method according to claim 13, comprising administering the oral liquid composition according to claim 1, wherein the amino acid is L - tryptophan, and the oral liquid composition according to claim 1, wherein the amino acid is L - tyrosine.

15. The method according to claim 14, wherein the oral liquid composition of L-tryptophan and the oral liquid composition of L-tyrosine are not administered on the same day.

16. The method according to claim 13, wherein the oral liquid composition of tryptophan is administered on the fourth day after childbirth, and the oral liquid composition of tyrosine is administered on the fifth day after childbirth.

17. The method according to claim 13, further comprising administering a solid or liquid oral liquid composition containing an antioxidant compound.

18. The method according to claim 17, wherein the additional antioxidant composition is administered on the third and fourth days after childbirth.

19. Use of an oral liquid composition according to claim 1, comprising an effective amount of one amino acid selected from L-tyrosine and L-tryptophan, at least one carbohydrate compound, water, and a pharmaceutically acceptable excipient, for the treatment or prevention of postpartum depression or depression in a subject in need thereof.

20. A kit for the treatment or prevention of postpartum depression or depressive mood in a subject in need thereof, (a) An oral liquid composition according to claim 4, comprising about 2 g of L-tryptophan per single dose, 50 - 60 g of a simple carbohydrate, at least one carbohydrate compound, water, and a pharmaceutically acceptable excipient; and (b) An oral liquid composition according to claim 1, comprising about 10 g of L-tyrosine and 50 - 60 g of a simple carbohydrate per single dose, comprising a kit.

21. A kit comprising a plurality of liquid compositions together with instructions for oral administration in a postpartum regimen for a plurality of days for the treatment or prevention of postpartum depression or depressive mood in a subject in need thereof, wherein the plurality of liquid compositions are A first composition and a second composition comprising 50 - 60 g of a carbohydrate and an antioxidant source, wherein the carbohydrate is 5% - 30% w / w based on the total liquid weight of the composition, and the first composition and the second composition are essentially free of amino acids and may be the same as or different from each other; A third composition comprising 50 - 60 g of a carbohydrate, an antioxidant source, and an amino acid comprising L-tryptophan, wherein the weight ratio of L-tryptophan to the carbohydrate is 1:10 - 1:40, and the carbohydrate is 5% - 30% w / w based on the total liquid weight of the composition; and A fourth composition comprising 50 to 60 g of carbohydrates, an antioxidant source, and an amino acid comprising L-tyrosine, wherein the weight ratio of the L-tyrosine to the carbohydrates is 1:2 to 1:30, and the carbohydrates are 5% to 30% w / w based on the total liquid weight of the composition, including the fourth composition, Instructions for the following administration, The first composition in the evening of the first day of the postnatal regimen; The second composition in the morning of the second day of the postnatal regimen; The third composition in the evening of the second day of the postnatal regimen; and The fourth composition in the morning of the third day of the postnatal regimen A kit containing.

22. The third composition comprises the L-tryptophan and the carbohydrates in a weight ratio of 1:20 to 1:35 or 1:25 to 1:30, The fourth composition comprises the L-tyrosine and the carbohydrates in a weight ratio of 1:3 to 1:15 or 1:4 to 1:10, The kit according to claim 21.

23. The first day of the regimen corresponds to the third day after the subject's childbirth; The antioxidant source comprises blueberry extract and / or blueberry juice; The carbohydrates are 20% to 30% w / w of the total weight of the composition The third composition comprises 1 to 5 g of L-tryptophan, or 2 g of L-tryptophan; One or more of the compositions are provided in the form of a shake; The carbohydrates comprise simple carbohydrates or sucrose; The fourth composition comprises 5 to 20 g of L-tyrosine, or 10 g of L-tyrosine; The antioxidant source comprises blueberry extract and / or juice showing 6500 ORAC units / g; and / or The composition further comprises one or more excipients or vehicles selected from the group consisting of a taste masking agent, a bitterness blocker, a sweetener, a flavor, a viscosity modifier, a thickening agent, guar gum, dietary fiber, and / or cocoa powder The kit according to claim 21 or claim 22.

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