Amino acid oral liquid composition

Abstract

An oral liquid composition comprising an effective amount of amino acids selected from L-tyrosine and L-tryptophan, carbohydrates, water, and optionally one or more acceptable excipients wherein the weight percentage of carbohydrates relative to the total weight of the composition is at least 5% w / w, and the weight ratio between amino acids and carbohydrates is 1: 1-1: 50. Methods of treating or preventing postpartum depression or depression using oral liquid compositions are described.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] 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 contents of which are incorporated herein by reference. Technical Field

[0003] The present invention relates to an oral liquid composition comprising amino acids selected from the group consisting of L-tryptophan and L-tyrosine, the liquid pharmaceutical composition being suitable for oral administration. Technical Background

[0004] Amino acids are essential dietary components obtained from protein contained in foods. Among the amino acids, L-tryptophan and L-tyrosine are unique in that they are precursors of brain neurotransmitters whose synthesis and release are sensitive to relatively small physiological changes in precursor concentrations (Fernstrom 1983).

[0005] 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, where it serves as a precursor for the powerful neurotransmitters serotonin, melatonin, and the vitamin niacin (vitamin B3). L-Tryptophan can be obtained from a variety of protein-rich foods in a normal diet, including meat, fish, milk and dairy products, eggs, beans, lentils, as well as bread and cereals, pasta, rice, fruits and vegetables. L-Tyrosine is an essential precursor for the synthesis of the catecholamine neurotransmitters adrenaline (epinephrine), noradrenaline (noradrenaline), dopamine, and thyroid hormones.

[0006] Changes in brain L-tryptophan concentrations alter the synthesis and release of serotonin (5-hydroxytryptamine), while changes in brain L-tyrosine concentrations alter the synthesis and release of catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine).

[0007] The concentration of amino acids in the brain is determined by the relative concentration of amino acids that cross the blood-brain barrier (BBB) ​​(Pardridge et al., 1975). Amino acids compete with structurally similar amino acids for active transport across this membrane. Tyrosine and tryptophan are both members of the large neutral amino acids (LNAA) class, which also includes phenylalanine, leucine, isoleucine, valine, histidine, and methionine (Belitz et al., 2009).

[0008] LNAA enters the brain via transporters located on capillary endothelial cells in the blood-brain barrier, which are saturable and competitive. The concentration of tryptophan or tyrosine in the brain is easily altered by its intake and the intake of other LNAAs, which share competing transporters for uptake from the circulation into the brain. The amount of tryptophan or tyrosine that actually enters the brain depends on the ratio of the amino acid in plasma to the sum of the plasma concentrations of LNAAs.

[0009] Therefore, physiological and pathophysiological factors that affect the blood concentrations of these LNAAs and other LNAAs that compete with them for co-transporters across the blood-brain barrier can predictably alter the concentrations of aromatic amino acids in the brain, the formation and release of these monoamine transmitters, and thus alter brain function (Fernstrom 1990, 1983). Therefore, treatments that affect the relative blood concentrations of L-tryptophan, L-tyrosine, and other large neutral amino acids can also affect the synthesis of brain neurotransmitters.

[0010] Due to their role in the serotonin pathway, supplementation of tyrosine and tryptophan levels is relevant for the medical treatment of different conditions such as depression, sleep disorders, cognitive impairment, anxiety disorders or neurodegenerative diseases.

[0011] International Patent Publication WO 2015188280 A1 (Meyer) discloses a method for treating or preventing postpartum depression in a subject in need thereof, the method comprising administering an antioxidant source, a tryptophan composition comprising 2 g of L-tryptophan, and a tyrosine composition comprising 10 g of L-tyrosine, wherein the antioxidant source is used at least once between the first and fifth days postpartum, the tryptophan composition is used to be administered at the same time as the antioxidant source or in the evening after the antioxidant source between the third and fifth days postpartum, and the tyrosine composition is administered the day after the administration of the tryptophan composition. In an embodiment, the antioxidant source is administered by combining a beverage composition comprising a blueberry juice concentrate with a capsule composition comprising a blueberry extract. Tryptophan is administered in the form of a 1 g tablet, and tyrosine is administered in the form of a 0.5 mg capsule. Both the beverage composition and the capsule composition contain sugar to make the treatment more acceptable to the subject. Sugar accounts for 9.25% w / w of the antioxidant composition. If sugar is not desired, other sweeteners may be used. To comply with this dosing regimen, subjects were instructed to drink concentrated blueberry juice combined with blueberry extract and to take either 2 capsules containing 1 gram of tryptophan each or 20 capsules containing 0.5 mg of tyrosine each, which may require clinical supervision.

[0012] Orally administrable liquid pharmaceutical compositions are attractive dosage forms for administration of prescribed dosage regimens. Liquid pharmaceutical compositions are easy to swallow and, if properly formulated, have an attractive taste, which can improve patient compliance with prescribed dosage regimens. Additionally, liquid pharmaceutical formulations provide better personalized dosing when compared to solid dosage forms, which can be important when treating different patient populations.

[0013] Oral solutions containing L-tyrosine or L-tryptophan known in the art generally contain less than 3% w / w carbohydrates (sugars) in their components. For example, patent publication WO 2004 / 047565 A1 (Tsunoo et al.) describes an amino acid oral solution containing tyrosine, citric acid, sucrose, trehalose and water for use as a temperature raising agent. The carbohydrates present in the composition account for 3% w / w of the total weight of the composition and are generally used as sweeteners or taste masking agents.

[0014] Drugs administered in the form of oral liquids are immediately absorbed from the digestive tract and can be absorbed faster than the same amount of drugs administered in tablets or capsules. However, in order to improve the brain's uptake of L-tyrosine and L-tryptophan, especially L-tryptophan, it is not enough to increase the serum concentrations of these two amino acids. Co-administration of L-tryptophan or L-tyrosine with other LNAAs leads to a depletion of the concentrations of these amino acids in the brain. For further considerations on the relative deficiency of tryptophan or tyrosine relative to LNAAs, reference may be made to: Gessa et al. 1974; Young et al. 1985; and Le Masurier et al., 2006.

[0015] Despite efforts, there remains a need for oral liquid formulations with efficient uptake of amino acids such as L-tryptophan or L-tyrosine. Summary of the invention

[0016] The inventors of the present application have developed an oral liquid composition comprising an effective amount of amino acids selected from the group consisting of L-tryptophan and L-tyrosine, which can avoid the problems associated with the prior art and increase patient compliance while maximizing the brain's uptake of the amino acids present in the composition.

[0017] The first aspect of the present invention is to provide an oral liquid composition comprising:

[0018] - an effective amount of an amino acid selected from L-tyrosine or L-tryptophan,

[0019] - at least one carbohydrate,

[0020] - Water, and

[0021] - one or more acceptable excipients,

[0022] The composition comprises more than 5% w / w carbohydrates based on the total weight of the composition, and the weight ratio between amino acids and carbohydrates is 1:1 to 1:50.

[0023] Without being bound by theory, the inventors believe that at low amounts below the 5% w / w level, the carbohydrate acts as a sweetener, but at amounts above 5%, the same carbohydrate can help promote the intake or absorption of amino acids incorporated into the composition by promoting an insulin response (Lee and Wolever, 1998). In other words, the carbohydrate acts as an adjuvant.

[0024] The second aspect of the present invention is to provide an oral liquid composition for use in a method for treating or preventing postpartum depression in a subject in need thereof, or for preparing a medicament for treating or preventing postpartum depression, comprising an effective amount of an amino acid selected from L-tyrosine and L-tryptophan, at least one carbohydrate, water, and one or more pharmaceutically acceptable excipients.

[0025] Also provided herein is a method for treating or preventing postpartum depression, and a corresponding use in treating or preventing postpartum depression, the method comprising administering to a subject in need thereof an oral liquid composition as defined in the first or second aspect of the present invention.

[0026] In a final aspect, the present invention also provides a kit comprising an oral liquid composition for the methods and uses of the present invention and instructions for use. DETAILED DESCRIPTION

[0027] Unless otherwise specified, all terms used in this application should be understood with ordinary meanings known in the art. Other more specific definitions of certain terms used in this application are described below and are intended to be uniformly applied throughout the description and claims, unless otherwise explicitly stated definitions provide a broader definition.

[0028] For purposes of the present invention, any range given includes the lower endpoint and the upper endpoint of the range.

[0029] As used herein, the meaning of the term "comprising" covers three options, namely, "including", "consisting of" and "consisting essentially of.

[0030] The term "oral liquid composition" refers to a liquid composition stored in physically discrete units suitable as single doses, which can be administered to a subject to provide the desired amount of 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 method of administration through the mouth.

[0031] As used herein, the term "baby blues" is defined as low mood and mild depressive symptoms (including sadness, tearfulness, fatigue, irritability, anxiety, decreased sleep, decreased concentration) and mood lability, which are transient and self-limited disorders that begin shortly after delivery.

[0032] As used herein, "therapeutically effective amount" refers to an amount effective at the dosage and for a period of time necessary to achieve the desired therapeutic outcome, such as one or more of the following therapeutic outcomes (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). A therapeutically effective amount is also generally an amount in which any toxic or deleterious effects of the active ingredient or pharmaceutical composition are outweighed by the therapeutically beneficial effects.

[0033] Therefore, the object of the present invention is 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.

[0034] In one embodiment, the oral liquid composition according to the present invention comprises an effective amount of L-tyrosine. Advantageously, the oral liquid composition comprises 1.0g to 50.0g of L-tyrosine, preferably 2.0g to 40.0g, more preferably 3.0g to 30.0g, and further preferably 5g to 20.0g of L-tyrosine. In a most preferred embodiment, the oral liquid composition according to the present invention comprises 5.0g, 6.0g, 7.0g, 8.0g, 9.0g, 10.0g, 11.0g, 12.0g, 13.0g, 14.0g, 15.0g, 16.0g, 17.0g, 18.0g, 19.0g or 20.0g of L-tyrosine. In a most preferred embodiment, the oral liquid composition according to the present invention comprises 10.0g of L-tyrosine.

[0035] In another embodiment, the oral liquid composition according to the present invention comprises an effective amount of L-tryptophan. Advantageously, the oral liquid composition comprises 0.5 g to 20.0 g of L-tryptophan, more preferably 1 to 10 g, and even more preferably 1 to 5 g. The oral liquid composition according to the present invention may comprise 1.0 g, 2.0 g, 3.0 g, 4.0 g or 5.0 g of L-tryptophan. In the most preferred embodiment, the composition according to the present invention comprises 2 g of L-tryptophan.

[0036] In some embodiments of the present invention, the oral liquid composition according to the present invention is substantially free of other amino acids selected from phenylalanine, leucine, isoleucine, valine, histidine and methionine to avoid partial consumption of tryptophan or tyrosine brain uptake in the composition of the present invention.

[0037] In the context of the present invention, "substantially free" means that the composition comprises the above mentioned amino acids in an amount of less than 2% w / w, particularly less than 1% w / w, in particular less than 0.5% w / w.

[0038] In some embodiments, the oral liquid composition according to the present invention comprises about 2 mg / mL to 100 mg / mL of L-tyrosine, preferably 3 mg / mL to 85 mg / mL, more preferably 5 mg / mL to 75 mg / mL, and further preferably 6 mg / mL to 65 mg / mL of L-tyrosine. In the most preferred embodiment, the oral liquid composition according to the present invention comprises 45 mg / mL to 55 mg / mL of L-tyrosine.

[0039] In a further embodiment, the oral liquid composition according to the present invention comprises 2.5 mg / mL to 100 mg / mL of L-tryptophan, preferably 3 mg / mL to 85 mg / mL, more preferably 5 mg / mL to 75 mg / mL, and further preferably 6 mg / mL to 65 mg / mL of L-tryptophan. In a most preferred embodiment, the oral liquid composition according to the present invention comprises 8 mg / mL to 12 mg / mL of L-tryptophan.

[0040] In one embodiment, the oral liquid composition according to the present invention comprises 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 comprises 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 more preferably greater than 15% w / w of the total weight of the composition.

[0041] In a further embodiment, the oral liquid composition according to the present invention comprises 50-60 g carbohydrates, preferably 53-57 g carbohydrates, wherein the carbohydrates are 5%-30% w / w relative to the total weight of the composition.

[0042] In some embodiments, carbohydrate is simple carbohydrate (sugar) or saccharide. In a preferred embodiment, saccharide is one or more or a combination thereof of glucose, galactose, fructose, xylose, sucrose, lactose, maltose, mannose, trehalose, sorbitol, mannitol, xylitol, raffinose, cellobiose, inulin, maltopolysaccharide, starch and cellulose. Preferably, saccharide is selected from sucrose, fructose and mixtures thereof.

[0043] In one embodiment, the oral liquid composition according to the present invention comprises a carbohydrate selected from sucrose, fructose or a mixture 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 preparation comprises at least one carbohydrate selected from sucrose, fructose or a mixture thereof at a concentration of 20% to about 25% w / w of the total weight of the composition. In a preferred embodiment, the carbohydrate is selected from sucrose, fructose or a mixture thereof, and is present in the preparation at a concentration higher than 5% w / w of the total weight of the composition, such as 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.

[0044] In some embodiments, the weight ratio of amino acids: carbohydrates is 1: 1 to 1: 50. In a preferred embodiment, the weight ratio of amino acids: carbohydrates is 1: 2 to 1: 40, more preferably 1: 3 to 1: 30. In a most preferred embodiment, the weight ratio of amino acids: carbohydrates is 1: 5 to 1: 26.

[0045] In one embodiment, the composition comprises L-tryptophan, and the weight ratio thereof relative to carbohydrate is 1:10 to 1:40, 1:20 to 1:35, or 1:25 to 1:30.

[0046] In alternative embodiments, the composition comprises L-tyrosine, and the weight ratio thereof relative to carbohydrate is 1:2 to 1:30, 1:3 to 1:15, 1:4 to 1:10.

[0047] In the present invention, the "amino acid:carbohydrate weight ratio" is defined as the ratio between the amount of amino acids versus the amount of carbohydrates, both amounts being expressed in the same unit (gram or milligram).

[0048] The oral liquid composition according to the present invention comprises 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 comprises about 68% to about 78% w / w of the total weight of the composition. In a most preferred embodiment, the oral liquid composition according to the present invention comprises about 72% to about 78% w / w of the total weight of the composition.

[0049] In a preferred embodiment, the liquid composition according to the invention comprises at least one ingredient having antioxidant properties.

[0050] As used herein, the term "antioxidant" refers to the ability of a substance to be included in an antioxidant composition, or may encompass a precursor compound that is converted to an antioxidant in the body after consumption.

[0051] The ingredients with antioxidant properties according to the invention may be of natural origin and are preferably obtained from plants. Such ingredients may be plant extracts or plant powders. Plants here include all parts of plants, such as leaves, bark, seeds or fruits such as berries.

[0052] Preferred components of plant origin having antioxidant properties are selected from the group comprising polyphenols, in particular plant polyphenols such as flavonoids, ellagitannins, xanthones, tannins and anthocyanidins. In a most preferred embodiment, the component having antioxidant properties and / or antioxidant enzyme catalytic properties is anthocyanidin. Anthocyanidins can be isolated from blueberries and can be administered as a blueberry extract.

[0053] In some embodiments, the ingredient having antioxidant properties may be selected from vitamin C, vitamin E, indole-3-carbinol, glutathione, or a mixture thereof.

[0054] 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 with nutritional or physiological effects, the purpose of which is to supplement the normal diet. In other words, a food supplement refers to any food, the purpose of which is to supplement the normal diet, and is a concentrated source of vitamins or minerals or other substances with nutritional or physiological effects, either alone or in combination. Food supplements are preferably sold in dosage form. The definition of "supplement" can be interpreted as taking in addition to the diet.

[0055] In another embodiment, the composition is a pharmaceutical or nutritional composition.

[0056] The oral liquid composition may optionally include 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.

[0057] In addition to sweeteners, liquid pharmaceutical or nutraceutical compositions may also include flavoring agents. Useful flavoring agents include various fruit flavors (e.g., orange, cherry, strawberry, grape, blueberry, etc.), mint, cocoa, chocolate, and vanilla flavors.

[0058] Oral liquid medicine or nutraceutical composition can optionally include viscosity control agent to increase the viscosity of composition. Increasing viscosity improves the handling of composition and seems to improve the taste of medicine or nutraceutical. Useful viscosity control agent comprises hydroxyethyl cellulose, xanthan gum, guar gum etc., they can be used alone or in combination. According to the present invention, preferred viscosity control agent is guar gum.

[0059] Viscosity control agents may be used in concentrations of at least about 0.001 mg / mL up to about 5 mg / mL.

[0060] Also provided herein is a method for treating or preventing postpartum depression and a corresponding use in treating or preventing / preventing postpartum depression, the method comprising administering to a subject in need thereof an oral liquid composition as defined in any one of the above aspects and embodiments.

[0061] As used herein, "treatment" refers to the postpartum depression or depression that occurs in the postpartum period in an individual who has experienced the symptoms and tendency of postpartum depression or depression in a way that leads to improvement. The improvement of postpartum depression or sadness can be quoted interchangeably with the improvement of postpartum depression or depression in this article. Treatment does not need to completely cure or eradicate individual depression or depression, but can simply alleviate one or more of the intensity or duration of the illnesses such as dysfunctional attitude, crying, irritability, inattention, change in appetite, tiredness, depression, anxiety, calm or nervous changes, restlessness, confusion, anger and / or fatigue. The improvement of mood can be determined by an individual, a health care professional, or can be determined using recognized parameters such as surveys, questionnaires or physiological tests. The improvement of symptoms that do not completely eradicate postpartum depression or depression is considered to be treatment. Treatment can be the reduction of symptom severity or duration determined by self-report or clinically accepted parameters (comprising questionnaires or behavioral assessment techniques) for assessing postpartum depression or depression.

[0062] As used herein, "prevention" or "prevention" of depression occurring in the postpartum period refers to addressing depression before it occurs in a manner that completely or partially prevents, delays, or reduces its occurrence. Prevention or prevention also encompasses addressing depression before it occurs or before a severe attack in a manner that reduces the severity, duration, or likelihood of recurrence of depression and its symptoms, thereby leading to improvement in the individual. "Prevention" and "prevention" do not mean that depression will not occur in an individual, but rather that measures are taken before the onset of depression in an individual in order to address the problem in advance. It is beneficial for individuals to adopt preventive or prevention strategies before the onset of the disease, and even if depression can only be partially prevented, it can be actively utilized. Methods and compositions for addressing depression are described in WO 2015 / 1188280 A1 (Meyer).

[0063] In one embodiment, the oral liquid composition of the present invention is administered to the subject between day 3 and day 5 postpartum.

[0064] In another embodiment, the oral liquid composition of the present invention is administered once, twice, or three times a day. In another embodiment, the oral liquid composition of the present invention is administered once a day.

[0065] In another embodiment, the method comprises administering an oral liquid composition of the present invention comprising an effective amount of L-tyrosine, which is effective in avoiding or alleviating symptoms, and / or is effective in treatment. In an alternative embodiment, the method comprises administering an oral liquid composition of the present invention comprising an effective amount of L-tryptophan, which is effective in avoiding or alleviating symptoms, and / or is effective in treatment. In an alternative embodiment, the method comprises administering an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tyrosine and an oral liquid composition comprising a therapeutically effective amount of L-tryptophan simultaneously, sequentially or separately. In an alternative embodiment, the method comprises administering an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tyrosine and an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tryptophan sequentially. In an alternative embodiment, the method comprises administering an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tyrosine and an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tryptophan sequentially and on different days. In an alternative embodiment, the method comprises administering an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tryptophan first, followed by administering an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tyrosine. In an alternative embodiment, the method comprises first administering an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tryptophan, followed by an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tyrosine, sequentially and on different days. In an alternative embodiment, the method comprises first administering an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tryptophan, and administering an oral liquid composition of the present invention comprising a therapeutically effective amount of L-tyrosine on the second day. In an alternative embodiment, L-tryptophan and L-tyrosine solutions are administered between day 1 and day 5 postpartum. In an alternative embodiment, between day 1 and day 5 postpartum, an L-tryptophan solution is administered first, followed by an L-tyrosine solution. In an alternative embodiment, between day 1 and day 5 postpartum, an L-tryptophan solution is administered first, and an L-tyrosine solution is administered on a different subsequent day.

[0066] In an alternative embodiment, the tryptophan composition is first administered on day 4 postpartum and the tyrosine oral liquid composition is administered on day 5 postpartum.

[0067] The method of the present invention may include administering at least another additional antioxidant composition in liquid or solid form that is substantially free of amino acids. In one embodiment, the additional antioxidant composition described above is administered alone. In one embodiment, the additional antioxidant composition in solid or liquid form is administered prior to administering the tryptophan composition. In another embodiment, the additional antioxidant composition in liquid or solid form is administered on postpartum day 3. In another embodiment, the antioxidant composition in liquid or solid form is administered on postpartum day 3 and day 4, the tryptophan composition is administered on postpartum day 4, and the tyrosine composition is administered on postpartum day 5.

[0068] According to another aspect, the oral liquid composition according to the present invention can be used as part of a multi-component kit. Such a kit suitable for treating or preventing postpartum depression or depression comprises:

[0069] a. An oral liquid composition comprising an effective amount of L-tryptophan, at least 5% w / w of at least one carbohydrate, water and optionally a pharmaceutically acceptable excipient, wherein the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:50;

[0070] b. An oral liquid composition comprising an effective amount of L-tyrosine, at least 5% w / w of at least one carbohydrate, water and optionally a pharmaceutically acceptable excipient, wherein the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:50; and

[0071] Instructions for administration of both compositions, for example, between day 4 and day 5 postpartum.

[0072] Typically, the kit also comprises an oral liquid beverage of at least one carbohydrate, water, at least one ingredient having antioxidant properties and optionally one or more acceptable excipients, which is administered 1 to 3 days postpartum.

[0073] According to a preferred embodiment, the medicine kit comprises:

[0074] a. An oral liquid composition comprising an effective amount of L-tryptophan, at least 5% w / w of at least one carbohydrate, water, at least one ingredient having antioxidant properties and optionally one or more acceptable excipients, wherein the weight ratio between amino acid and carbohydrate is 1:1 to 1:50;

[0075] b. An oral liquid composition comprising an effective amount of L-tyrosine, at least 5% w / w of at least one carbohydrate, water, at least one ingredient having antioxidant properties and optionally one or more acceptable excipients, wherein the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:50;

[0076] c. an oral composition in liquid or solid form comprising at least one carbohydrate, water, at least one ingredient having antioxidant properties and optionally one or more acceptable excipients, wherein the oral composition is substantially free of amino acids; and

[0077] Instructions for administration, such as instructions for administration between day 1 and day 5 postpartum.

[0078] The oral solid composition comprising the antioxidant ingredient may take the form of, for example, pills, 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.

[0079] The kit of the present invention provides instructions for administration of the oral liquid composition of the present invention as provided in any of the above embodiments involving administration of the formulation (separately, sequentially, simultaneously; in different or the same manner; in the specific case of postpartum depression, a specific dosage regimen, etc.). Therefore, the above embodiments provided under the methods of treatment and prevention are also embodiments when using the kit of the present invention.

[0080] According to additional aspects, the kit comprises a plurality of liquid compositions and instructions for oral administration in a multi-day postpartum regimen for treating or preventing postpartum blues or depressive mood in a subject in need thereof.

[0081] Various liquid compositions include:

[0082] a first composition and a second composition comprising 50 g to 60 g of a carbohydrate and a source of antioxidants, wherein the carbohydrate is 5% to 30% w / w relative to the total liquid weight of the composition, and wherein the first composition and the second composition are substantially free of amino acids and may be the same or different from each other;

[0083] A third composition comprising 50 g to 60 g of carbohydrate, an antioxidant source, and an amino acid consisting of L-tryptophan, wherein the weight ratio of L-tryptophan to carbohydrate is 1:10 to 1:40, and the carbohydrate is 5% to 30% w / w relative to the total liquid weight of the composition; and

[0084] A fourth composition comprising 50 g to 60 g of carbohydrate, an antioxidant source, and an amino acid consisting of L-tyrosine, wherein the weight ratio of L-tyrosine to carbohydrate is 1:2 to 1:30, and the carbohydrate is 5% to 30% w / w relative to the total liquid weight of the composition; and

[0085] Instructions for oral administration in a multi-day postpartum regimen for treating or preventing postpartum blues or depressive mood in a subject in need thereof.

[0086] For example, the instructions can direct administration of: a first composition on the evening of the first day of the postpartum regimen; a second composition on the morning of the second day of the postpartum regimen; a third composition on the evening of the second day of the postpartum regimen; and a fourth composition on the morning of the third day of the postpartum regimen.

[0087] For example, the third composition may comprise L-tryptophan and carbohydrates in a weight ratio of 1:20 to 1:35 or 1:25 to 1:30; and the fourth composition may comprise L-tyrosine and carbohydrates in a weight ratio of 1:3 to 1:15 or 1:4 to 1:10.

[0088] The kit may also have one or more of the following features: the first day of the regimen may correspond to the third day postpartum of the subject; the antioxidant source may include blueberry extract and / or blueberry juice; the carbohydrates may be 20% to 30% w / w of the total weight of the composition; the third composition may include 1 to 5g L-tryptophan, for example 2g L-tryptophan; the fourth composition may include 5 to 20g L-tyrosine, for example 10g L-tyrosine; one or more compositions may be provided in the form of a milkshake; the carbohydrates may include simple carbohydrates, such as sucrose; the antioxidant source may include blueberry extract and / or blueberry juice providing 6500 ORAC units / gram; and / or the composition may also include an excipient or vehicle selected from the group consisting of: taste masking agents, bitterness blocking agents, sweeteners, flavoring agents, viscosity control agents, thickeners, guar gum, fiber, cocoa powder and combinations thereof.

[0089] The following examples are intended to be illustrative rather than limiting and represent specific embodiments of the present invention.

[0090] Example 1

[0091] L-Tryptophan Oral Solution

[0092] The following oral solution summarized in Table 1 is an example of an oral amino acid solution, wherein the ratio of the amino acid L-tryptophan to carbohydrates (primarily sucrose) is about 2g:55.84g (or about 1:27.92). In addition, when expressed as a weight percentage of the total weight of the composition, the carbohydrates from sucrose are 21.38%. The single serving weight shown in Table 1 is 261.274g and is to be consumed in one go, with a sugar content of 55.84g per serving, and therefore has a high sugar content, which aids in the absorption and uptake of the amino acid content. Excipients are present in this exemplary oral solution, and the blueberry extract contributes antioxidant capacity to the solution. The solution can be delivered in the form of a finished solution, which can be shaken to enhance mixing and mouthfeel.

[0093]

[0094]

[0095] ** Blueberry extract provides 6500 ORAC units / gram

[0096] Example 2

[0097] L-Tyrosine Oral Solution

[0098] The following oral solution in Table 2 is an example of an amino acid oral solution, wherein the ratio of the amino acid L-tyrosine to carbohydrates (mainly sucrose) is about 10.204 g:55.84 g (or about 1:5.45). In addition, when expressed as a weight percentage of the total weight of the composition, the carbohydrates from sucrose are 20.78%. The single serving weight shown in Table 2 is 268.678 g, and is to be consumed at one time, with a sugar content of 55.84 g per serving, and therefore has a high sugar content, which aids in the absorption and uptake of the amino acid content. Excipients are present in this exemplary oral solution, and the blueberry extract contributes antioxidant capacity to the solution. The solution can be delivered in the form of a finished solution, which can be shaken to enhance mixing and mouthfeel.

[0099]

[0100] ** Blueberry extract provides 6500 ORAC units / gram

[0101] Example 3 (reference)

[0102] Beverages containing antioxidants

[0103] The following oral solution summarized in Table 3 is an example of a reference amino acid oral solution without amino acids. The carbohydrates present (primarily sucrose) are approximately 55.84 g. When expressed as a weight percentage of the total weight of the composition, the carbohydrates from sucrose are 21.35%. The single serving weight shown in Table 3 is 261.474 g and is to be consumed as a single serving. Excipients are present in this exemplary oral solution, and the blueberry extract contributes antioxidant capacity to the solution. The solution can be delivered as a finished solution, which can be shaken to enhance mixing and mouthfeel.

[0104]

[0105] ** Blueberry extract provides 6500 ORAC units / gram

[0106] Example 4

[0107] Compositions for use in postpartum subjects

[0108] To complete the study, healthy pregnant women in their third trimester with no history of a major depressive episode (MDE) were recruited. Subjects will be randomized in a double-blind fashion to placebo or active supplement groups, with 2, 4, 6, 8, or 10 subjects in each group. Supplement / placebo will be taken at 4 time points, from the evening of postpartum day 3 to the morning of postpartum day 5 (see full schedule below). Subjects will receive either a liquid formulation or a placebo matched in taste and color.

[0109] Administration schedule of investigational product:

[0110] - Postpartum day 3 evening: Participants drank the antioxidant liquid composition disclosed in Example 3 or the placebo liquid composition.

[0111] - On the morning of postpartum day 4, the participants drank the antioxidant liquid composition disclosed in Example 3 or the placebo liquid composition.

[0112] - Postpartum day 4 evening: Participants drank the tryptophan liquid composition disclosed in Example 1 or a placebo liquid composition.

[0113] - Morning of postpartum day 5: Participants drank the tyrosine liquid composition disclosed in Example 2 or a placebo liquid composition.

[0114] On day 5, after administration of the liquid composition, participants were asked to complete the following documents:

[0115] - Pittsburgh Sleep Quality Index. This questionnaire is used to assess the sleep quality of the subjects.

[0116] - First, subjects underwent a neutral emotion induction process (MIP) based on the Velten MIP, which is the most widely used technique for studying the influence of emotion on behavior and has demonstrated its effectiveness in changing subjective emotional states (Frost et al., 1982).

[0117] After the neutral MIP, subjects will fill out the following questionnaires in the prescribed order:

[0118] a. Visual Analog Scale (VAS) Participants use a 10-point scale to indicate how consistent each of the 8 items is with how they feel at the moment; items include depression, happiness, restlessness, sadness, anxiety, anger, drowsiness, and alertness. In the VAS, the mood assessment will be conducted first.

[0119] b. The Dysfunctional Attitudes Scale (DAS), which is designed to identify and measure cognitive distortions, particularly those that may be associated with or contribute to depression.

[0120] c. The Profile of Mood States Scale (POMS) contains 65 adjectives rated by participants on a 5-point scale. Six factors were obtained, including nervous, depressed, angry, tired, energetic, and confused.

[0121] d. VAS

[0122] e. The State-Trait Anxiety Inventory consists of two scales, each containing 20 items. One scale addresses state anxiety, while the other addresses trait anxiety. The total score indicates which type of anxiety is prevalent and distinguishes a person's state versus trait anxiety levels.

[0123] -Secondly, the subjects underwent a sadness mood induction based on the Velten MIP. After the sadness MIP, the subjects repeated the above questionnaires in the prescribed order.

[0124] -After completing the above questionnaire, the subjects undergo the Emotional Stroop Test. This test is used as an information processing method to assess emotions. The Emotional Stroop Test works by checking the response time of the participants to say the color of negative emotional words.

[0125] -VAS

[0126] -Subjects will experience a neutral mood induction

[0127] -VAS

[0128] - Beck Depression Inventor Scale (BDI), Standardized Health Questionnaire

[0129] -Edinburgh Postnatal Depression Scale (EPDS), a standardized health questionnaire

[0130] -Stein Blue Scale is a self-report measure consisting of 13 symptoms (depression, crying, anxiety, tension, restlessness, fatigue, dreaming, appetite, headache, irritability, inattention, forgetfulness and confusion).

[0131] -Kennerley and Gath is a self-report 28-item depression questionnaire.

[0132] -HAM-D, a standardized health questionnaire

[0133] -Center Epidemiologic Studies Depression Scale (CES-D) 165, a 20-item depression scale with scores ranging from 0 (least depressed) to 60 (most depressed).

[0134] - Safety and tolerability checklist

[0135] - Food records on the evening of the 4th day after delivery and the morning of the 5th day after delivery

[0136] Primary analyses used repeated measures ANOVA with a visual analogue scale of depressive mood as the repeated measure (before and after the sadness MIP) and active condition versus placebo as the between-subjects measure.

[0137] A secondary analysis of changes in depression scores on the Profile of Mood States (POMS) scale was performed using repeated measures ANOVA with POMS scores as the repeated measure (before and after the Sadness MIP) and active state versus placebo as the between-subjects measure.

[0138] The methodology and timeline for evaluating, recording, and analyzing safety parameters are as follows.

[0139] Adverse events were recorded in the adverse event log. The principal investigator was consulted to determine the reasonable causal relationship to the investigational product and the severity of the event. Adverse events were collected until the end of the study on postpartum day 5.

[0140] Example 5

[0141] Ready-made milkshake for treating or preventing postpartum blues or depression

[0142] Kits containing multiple liquids are packaged together for use as a multi-day regimen for postpartum individuals who are experiencing or wish to preventively avoid the baby blues or depressive mood.

[0143] For example, the kit may come with four sealed containers, each labeled with the time of day to be consumed in a multi-day regimen, such as the morning or evening of day 1 (corresponding to day 3 postpartum), day 2 (corresponding to day 4 postpartum), or day 3 (corresponding to day 5 postpartum) of the regimen. The convenience of the finished liquid form in a sealed container allows the user to refrigerate and fully shake the container before use, which can mobilize stabilizers and other excipients such as thickeners to obtain a thick and consistent mouthfeel. The convenience of the finished product being consumed as planned during the tense and chaotic postpartum period encourages easy compliance as parents adjust to many aspects of their situation in such a short period of time after delivery. Clear labeling of each container and the easy-to-follow instructions of the kit also help to improve compliance.

[0144] The sugar content of each individual container (representing one portion) may be in the range of 40 to 65, for example 55 to 58 g per portion. The tyrosine or tryptophan content of a single portion may be, for example: 2 g L-tryptophan (as in Example 1, Table 1), or 10 g L-tyrosine (as in Example 2, Table 2).

[0145] The size of each container can be tailored to be consistent with the other containers in the kit, and can be in the range of 250-300 mL, representing a reasonable volume for an individual to consume at one time.

[0146] Thickeners and other ingredients that produce a pleasing mouthfeel representative of a "milkshake" make the product more pleasing to the subject.

[0147] The product is prepared in a convenient form that is easy to subsequently package in a kit format, while ensuring that the formulation is refreshing, tasty, fruity and healthy, encouraging subject compliance. For example, 4 different but clearly labeled bottles can be sold in a pre-packaged box with easy-to-follow instructions that can be optionally refrigerated and shaken before opening. The instructions for use can follow the protocol outlined by Meyer (2015) in WO 2015188280 A1, for example.

[0148] A sample scenario could be as follows:

[0149]

[0150] References

[0151] The following documents are incorporated herein by reference.

[0152] Belitz HD et al.Food Chemistry,4 th revised and extended edition,2009,Springer-Verlag Berlin Heidelberg.Chapter 1Amino Acids,Peptides,Proteins.pages 8-92.

[0153] Fernstrom et al.(1983).Role Of Precursor Availability In The ControlOf Monoamine Biosynthesis In Brain.Physiol.Rev 1983,63,484-546.

[0154] Fernstrom et al. (1990). Aromatic amino acids and monoamine synthesis in the central nervous system: influence of the diet. J. Nutr. Biochem. 1990, 1, 508-17.

[0155] Frost et al.(1982)Mood Induction Procedure Effects:Duration and Post-experimental Removal.Personality and Social Psychology Bulletin 1982,8,341-347.

[0156] Gessa et al.(1974)Effect of the oral administration of tryptophan-free amino acid mixtures on serum tryptophan,brain tryptophan,and serotoninmetabolism.J.Neurochem1974,22,869–870.

[0157] Lee and Wolever(1998)Effect of Glucose,Sucrose and Fructose on PlasmaGlucose and Insulin Responses in Normal Humans:Comparison with WhiteBread.European Journal of Clinical Nutrition 1998,52,924-928.

[0158] Le Masurier et al.(2006)Effect of Acute Tyrosine Depletion in Using aBranched Chain Amino-Acid Mixture on Dopamine Neurotransmission in the RatBrain.Neuropsychopharmacology 2006,31,310–317.

[0159] Meyer(2015)Methods and Compositions Addressing DepressedMood.International Patent Application PCT / CA2015 / 050548filed June 12,2015published as WO 2015188280A1 on December 17,2015.

[0160] Pardridge et al.(1975).Kinetic Analysis Of Blood Brain BarrierTransport Of Amino Acids.Biochim Biophys.Acta 1975,401,128-136.

[0161] Young et al. (1985) Biochemical aspects of tryptophan depletion inprimates. Psychopharmacology 1985,98,508–511.

[0162] Tsunoo et al.(2004)Agent for Foods,Drinks or Medical Uses ContainingBody Temperature-Elevating Amino Acid.WO 2004 / 047565 A1 published June 10,2004.

[0163] Terms

[0164] For reasons of completeness, various aspects of the invention are set out in the following numbered clauses:

[0165] Item 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 weight percentage of the carbohydrate relative to the total weight of the composition is at least 5% w / w, and the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:50.

[0166] Item 2. An oral liquid composition according to Item 1, wherein:

[0167] The amino acid is L-tyrosine, and the weight ratio of carbohydrate to the amino acid is in excess, in particular the weight ratio between L-tyrosine and carbohydrate is 1:2 to 1:30, 1:3 to 1:15 or 1:4 to 10; or, alternatively,

[0168] The amino acid is L-tryptophan, and the weight ratio of carbohydrate to the amino acid is excessive, particularly the weight ratio between L-tryptophan and carbohydrate is 1:10 to 1:40, 1:20 to 1:35 or 1:25 to 1:30.

[0169] Item 3. An oral liquid composition according to Item 1 or 2, wherein the % w / w of carbohydrates based on the total weight of the composition is about 5% to about 50% w / w, or about 10% to about 40% w / w, or about 15% to about 30% w / w.

[0170] Item 4. An oral liquid composition according to any one of items 1 to 3, wherein the oral liquid composition comprises 5 g to 20.0 g L-tyrosine, in particular 10 g L-tyrosine.

[0171] Item 5. An oral liquid composition according to any one of items 1 to 4, wherein the oral liquid composition comprises 1 g to 10 g of L-tryptophan, in particular 2 g of L-tryptophan.

[0172] Item 6. An oral liquid composition according to any one of Items 1 to 5, wherein the composition comprises 3 mg / mL to 75 mg / mL of L-tyrosine or L-tryptophan.

[0173] Item 7. An oral liquid composition according to any one of Items 1 to 6, further comprising at least one ingredient having antioxidant properties.

[0174] Item 8. An oral liquid composition according to Item 7, wherein the ingredient having antioxidant properties is selected from the group consisting of flavonoids, ellagitannins, xanthones, tannins, anthocyanins, vitamin C, vitamin E, indole-3-carbinol, glutathione and mixtures thereof.

[0175] Item 9. An oral liquid composition according to any one of items 1 to 8, wherein the composition is substantially free of other amino acids selected from phenylalanine, leucine, isoleucine, valine, histidine and methionine.

[0176] Item 10. An oral liquid composition according to any one of Items 1 to 9, wherein the composition comprises one or more suitable excipients or vehicles selected from taste masking agents, bitterness blocking agents, sweeteners, flavoring agents and viscosity control agents.

[0177] Item 11. A composition according to any one of items 1 to 10 which is a food supplement and comprises an edible acceptable excipient.

[0178] Clause 12. A composition according to any one of clauses 1 to 10, which is a pharmaceutical composition and comprises a pharmaceutically acceptable excipient.

[0179] Clause 13. A medicine kit:

[0180] a. An oral liquid composition as defined in any one of clauses 1 to 12, wherein the amino acid is L-tryptophan;

[0181] b. An oral liquid composition as defined in any one of clauses 1 to 12, wherein the amino acid is L-tyrosine;

[0182] and

[0183] Instructions for administration of both compositions.

[0184] Clause 14. A pharmaceutical kit according to clause 13, comprising:

[0185] a. An oral liquid composition as defined in any one of clauses 1 to 12, wherein the amino acid is L-tryptophan;

[0186] b. An oral liquid composition as defined in any one of clauses 1 to 12, wherein the amino acid is L-tyrosine;

[0187] c. a liquid or solid oral composition comprising at least one carbohydrate, water, at least one ingredient having antioxidant properties and optionally one or more acceptable excipients, wherein the oral liquid solution is substantially free of amino acids; and

[0188] Instructions for use.

[0189] Item 15. A method for treating or preventing postpartum depression in a subject in need thereof, the method comprising administering an oral liquid composition as defined in any one of Items 1 to 12, the oral liquid composition comprising a therapeutically effective amount of an amino acid selected from L-tyrosine and L-tryptophan, at least one carbohydrate, water and a pharmaceutically acceptable excipient, or alternatively, using a pharmaceutical kit as defined in Item 13 or 14.

[0190] Item 16. The method according to Item 15, wherein the tryptophan oral liquid composition and the tyrosine oral liquid preparation are not administered on the same day.

[0191] Item 17. The method according to Item 15 or 16, wherein the tryptophan oral liquid composition is administered on the 4th day after delivery, and the tyrosine oral liquid composition is administered on the 5th day after delivery.

[0192] Clause 18. A method according to any one of clauses 15 to 17, further comprising administering an oral liquid composition comprising an antioxidant compound as defined above.

[0193] Clause 19. The method according to Clause 18, wherein the additional antioxidant compound is administered on day 3 postpartum.

[0194] Clause 20. The method according to Clause 19, wherein the additional antioxidant compound is further administered on day 4 postpartum.

[0195] Clause 21. A kit comprising a plurality of liquid compositions and instructions for oral administration in a multi-day postpartum regimen for treating or preventing postpartum blues or depressive mood in a subject in need thereof, the plurality of liquid compositions comprising:

[0196] The first composition and the second composition contain 50 g to 60 g of carbohydrate and an antioxidant source, wherein

[0197] 5% to 30% w / w carbohydrate relative to the total liquid weight of the composition, wherein the first and second compositions are substantially free of amino acids and may be the same or different from each other;

[0198] A third composition comprising 50 g to 60 g of carbohydrate, an antioxidant source, and an amino acid consisting of L-tryptophan, wherein: the weight ratio of L-tryptophan to carbohydrate is 1:10 to 1:40, and the carbohydrate is 5% to 30% w / w relative to the total liquid weight of the composition; and

[0199] A fourth composition comprising 50 g to 60 g of carbohydrate, an antioxidant source, and an amino acid consisting of L-tyrosine, wherein: the weight ratio of L-tyrosine to carbohydrate is 1:2 to 1:30, and the carbohydrate is 5% to 30% w / w relative to the total liquid weight of the composition; and

[0200] Instructions for use:

[0201] Administer the first composition on the evening of the first day of the postpartum regimen;

[0202] The second composition is administered on the morning of the second day of the postpartum regimen;

[0203] administering a third composition on the second evening of the postpartum regimen; and

[0204] The fourth composition is administered on the morning of the third day of the postpartum regimen.

[0205] Clause 22. The pharmaceutical kit of clause 21, wherein:

[0206] The third composition comprises L-tryptophan and carbohydrates in a weight ratio of 1:20 to 1:35 or 1:25 to 1:30;

[0207] as well as

[0208] The fourth composition comprises L-tyrosine and carbohydrate in a weight ratio of 1:3 to 1:15 or 1:4 to 1:10.

[0209] The pharmaceutical kit of clause 23, clause 21 or 22, wherein:

[0210] The first day of the protocol corresponded to the subjects’ postpartum day 3;

[0211] The antioxidant source comprises blueberry extract and / or blueberry juice;

[0212] Carbohydrates account for 20% to 30% w / w of the total weight of the composition;

[0213] The third composition comprises 1 g to 5 g of L-tryptophan or 2 g of L-tryptophan;

[0214] One or more of the compositions are provided in the form of a milkshake;

[0215] Carbohydrates include simple carbohydrates or sucrose;

[0216] The fourth composition comprises 5 g to 20 g of L-tyrosine or 10 g of L-tyrosine;

[0217] The antioxidant source comprises blueberry extract and / or juice providing 6500 ORAC units / gram; and / or

[0218] The composition further comprises one or more excipients or vehicles selected from the group consisting of taste masking agents, bitterness blocking agents, sweeteners, flavoring agents, viscosity control agents, thickeners, guar gum, fiber and / or cocoa powder.

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 weight percentage of the carbohydrate relative to the total weight of the composition is at least 5% w / w, and the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:

50.

2. The oral liquid composition according to claim 1, wherein: The amino acid is L-tyrosine, and the carbohydrate is in excess relative to the amino acid by weight, particularly the weight ratio of L-tyrosine to the carbohydrate is 1:2 to 1:30, 1:3 to 1:15 or 1:4 to 1:10; or, alternatively, The amino acid is L-tryptophan, and the weight ratio of the carbohydrate to the amino acid is excessive, and in particular the weight ratio of L-tryptophan to the carbohydrate is 1:10-1:40, 1:20-1:35 or 1:25-1:

30.

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

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

5. The oral liquid composition of claim 1, further comprising at least one ingredient having antioxidant properties.

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

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

8. The composition of claim 1 which is a food supplement.

9. The composition of claim 1, which is a pharmaceutical composition and comprises a pharmaceutically acceptable excipient.

10. A medicine kit comprising: a. An oral liquid composition comprising an effective amount of L-tryptophan, at least one carbohydrate in an amount of at least 5% w / w, water and an optional pharmaceutically acceptable excipient, wherein the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:50; b. An oral liquid composition comprising an effective amount of L-tyrosine, at least one carbohydrate having a weight percentage of at least 5% w / w, water and an optional pharmaceutically acceptable excipient, wherein the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:50; and Instructions for administration of both compositions.

11. A pharmaceutical kit comprising: a. An oral liquid composition comprising an effective amount of L-tryptophan, at least one carbohydrate in an amount of at least 5% w / w, water, at least one ingredient having antioxidant properties and optionally one or more acceptable excipients, wherein the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:50; b. An oral liquid composition comprising an effective amount of L-tyrosine, at least one carbohydrate in an amount of at least 5% w / w, water, at least one ingredient having antioxidant properties and optionally one or more acceptable excipients, wherein the weight ratio between the amino acid and the carbohydrate is 1:1 to 1:50; c. a liquid or solid oral composition comprising at least one carbohydrate, water, at least one ingredient having antioxidant properties and optionally one or more acceptable excipients, wherein the antioxidant composition is substantially free of amino acids; and Instructions for use.

12. The oral liquid composition of claim 5 or the kit of claim 11, wherein the ingredient having antioxidant properties 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 treating or preventing postpartum blues or depression in a subject in need thereof, the method comprising administering an oral liquid composition as defined in claim 1, the composition comprising a therapeutically effective amount of an amino acid selected from L-tyrosine and L-tryptophan, the at least one carbohydrate, water and a pharmaceutically acceptable excipient; or, alternatively, the method comprises using a pharmaceutical kit as defined in claim 10 or 11.

14. The method of claim 13, comprising administering an oral liquid composition as defined in claim 1, wherein the amino acid is L-tryptophan, and an oral liquid composition as defined in claim 1, wherein the amino acid is L-tyrosine.

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

16. The method of claim 13, wherein the tryptophan oral liquid composition is administered on day 4 postpartum and the tyrosine oral liquid composition is administered on day 5 postpartum.

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

18. The method of claim 17, wherein the additional antioxidant composition is administered on days 3 and 4 postpartum.

19. Use of an oral liquid composition as defined in claim 1, comprising an effective amount of an amino acid selected from L-tyrosine and L-tryptophan, said at least one carbohydrate, water and a pharmaceutically acceptable excipient, for treating or preventing postpartum depression or depression in a subject in need thereof.

20. A kit for treating or preventing postpartum depression or depressive mood in a subject in need thereof, the kit comprising: (a) an oral liquid composition as defined in claim 4, comprising per serving about 2 g of L-tryptophan and 50 g to 60 g of simple carbohydrates, said at least one carbohydrate, water and a pharmaceutically acceptable excipient; and (b) one or more servings of the oral liquid composition as defined in claim 1, each serving comprising about 10 g of L-tyrosine and 50 g to 60 g of simple carbohydrates.

21. A kit comprising a plurality of liquid compositions and instructions for oral administration in a multi-day postpartum regimen for treating or preventing postpartum blues or depressive mood in a subject in need thereof, the plurality of liquid compositions comprising: a first composition and a second composition comprising 50 g to 60 g of a carbohydrate and a source of antioxidants, wherein the carbohydrate is 5% to 30% w / w relative to the total liquid weight of the composition, wherein the first composition and the second composition are substantially free of amino acids and may be the same or different from each other; The third composition comprises 50 g to 60 g of carbohydrates, an antioxidant source and an amino acid consisting of L-tryptophan, wherein: The weight ratio of L-tryptophan to carbohydrate is 1:10 to 1:40, and the carbohydrate is 5% to 30% w / w relative to the total liquid weight of the composition; and A fourth composition comprising 50 g to 60 g of carbohydrate, an antioxidant source and an amino acid consisting of L-tyrosine, wherein: the weight ratio of L-tyrosine to carbohydrate is 1:2 to 1:30, and the carbohydrate is 5% to 30% w / w relative to the total liquid weight of the composition; and Instructions for use: administering said first composition on the evening of the first day of said postpartum regimen; administering the second composition on the morning of the second day of the postpartum regimen; administering the third composition on the second evening of the postpartum regimen; and The fourth composition is administered on the morning of the third day of the postpartum regimen.

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

10.

23. A kit as claimed in claim 21 or 22, wherein: The first day of the regimen corresponds to postpartum day 3 for the subject; 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 comprises 1 g 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 milkshake; The carbohydrate comprises simple carbohydrates or sucrose; The fourth composition comprises 5 g to 20 g of L-tyrosine or 10 g of L-tyrosine; The antioxidant source comprises blueberry extract and / or juice providing 6500 ORAC units / gram; and / or The composition further comprises one or more excipients or vehicles selected from the group consisting of taste masking agents, bitterness blocking agents, sweeteners, flavoring agents, viscosity control agents, thickeners, guar gum, fiber and / or cocoa powder.

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