Sleep promoting peptides and the use thereof

Abstract

Sleep promoting peptides and compositions comprising sleep promoting peptides are provided. The peptides and the compositions have a use to promote sleep in a subject. Specific peptides are described in SEQUENCE ID NO. 1 to 139.

Description

Title of the inventionSleep promoting peptides and the use thereof.Field of the InventionThe current invention relates to peptides and compositions comprising said peptides. The peptides of the invention have sleep promoting activity. The current invention also relates to the use of peptides and compositions of the invention.Background to the InventionSleep is essential for human health and well-being. The importance of sleep as a risk factor for poor health is often overlooked. Lack of sleep can have detrimental effects on cognition, anxiety, mental health, energy levels, cardiovascular and metabolic health. Beyond personal health, sleep quantity and quality can impact workplace performance, relationships, accidents on the road, the workplace or at home and therefore, represents a risk to public health and safety (Ramar, Malhotra, Carden et al., (2021) J Clin Sleep Med, 17(10), pp. 2115-2119).Sleep quality can be impacted by a myriad of factors spanning from untreated sleep disorders to lifestyle habits and certain medications. However, one of the most common factors impacting sleep is stress.Stress has become a serious social issue and can have a two-fold impact on sleep. Lifestyle stressors like finances, work pressures or family issues, can often hamper the process of falling asleep, shortening, and fragmenting the period of rest, which has knock on effects for brain health, memory, and cellular restoration. Furthermore, sleep loss can trigger the endogenous stress response system and acute activation of stress hormones, such as cortisol, which can not only disturb sleep quality but also accelerate metabolic and cognitive consequences over time (Leproult, Copinschi, Buxton et al., (1997) Sleep 20(10):865-70.). Cortisol is a steroid hormone produced by the adrenal gland on top of the kidneys which promotes wakefulness and is elevated during period of stress.The transition from wakefulness to sleep is based on several mechanisms, the human circadian rhythm and sleep-wake homeostasis. The human circadian rhythm works on a 24- hour basis and stimulates many of the body’s daily functions, including body temperature, metabolism, and hormone release. It enables the body to initiate sleep by evoking feelings of tiredness through activation and / or inhibition of key hormones and neurotransmitters which include, norepinephrine, serotonin, acetylcholine, histamine, dopamine, and orexin to name a few (Valentio & Volkow (2019) Nature Publishing Group, pp. 1-3). The sleep-wake homeostasis mechanism acknowledges internal and external influences that may impact an individual’s sleep such as stress, nutrition, medical conditions or exposure to light.There are a wide range of sleep aids and hypnotics available on the market either by prescription or over the counter. They vary from small molecules to natural ingredients some of which target known sleep-enhancing pathways, such as the y-aminobutyric acid (GABA) and melatonin receptors, histamine-1 receptors, and orexin receptors. Some of the small molecule ingredients fall into one of four categories, namely (1) non-benzodiazepines, e.g. Eszopiclone and Diphenhydramine or DHH, (2) benzodiazepines, e.g. Flurazepam, (3) melatonin receptor agonists, e.g. Rameltron, and (4) orexin receptor antagonists, e.g. Suvorexant.Importantly, the above-listed medications should only be taken for a short period of time due to the likelihood of developing dependence, habituation, and tolerance. Further undesirable side effects associated with prescription sleep aids include headaches and drowsiness. One of the biggest limitations of prescription medications is that while they do promote sedation and a state of unconsciousness, they fail to induce rapid eye movement (REM) sleep, the most restorative stage of sleep (Newman & Alschuler (2022) Journal of Interprofessional Education & Practice 29:100569.).Another limitation associated with such drugs is their possibility to enhance the sedative effects of depressants and / or other drugs. Further investigations on the potential complications associated with long-term use of prescribed sleep medications is required as clinical research on this complex area is limited.Orexin is a neurotransmitter that regulates a variety of physiological functions including sleepwake cycles, appetite, memory, and the stress response (Wang et al., (2018) Frontiers in Molecular Neuroscience. Frontiers Media S.A.). This has been a successful target for sleep medications such as the small molecule orexin receptor antagonist, Suvorexant, which has been shown to suppress abnormal sleep behaviour. Unfortunately, small molecule therapeutics are notoriously associated with off-target effects and unfavourable safety profiles. In addition, Suvorexant’s high cost makes it unaffordable for many suffering with sleep disruption.Prescription sleep aids are commonly prescribed; however, they can lead to undesirable side effects, such as headaches, drowsiness, tolerance, and dependency. One of the biggest limitations of these medications is that while they do promote sedation and a state of unconsciousness, they fail to induce rapid eye movement (REM) sleep, the most restorative stage of sleep (Newman & Alschuler (2022) Journal of Interprofessional Education & Practice 29:100569.).Natural alternatives exist with melatonin, ashwagandha, valerian and magnesium being some of the most studied. However, there is a lack of high-quality research and scientific consensuson the effectiveness and safety of many natural sleep aids (Guadagna, Barattini, Rosu et al., (2020) Evid Based Complement Alternat Med. 2020:3792390).The lack of effective solutions makes finding a natural, safe, validated nutritional intervention that promotes relaxation, reduces stress, and encourages healthy sleep an urgent unmet need.The current invention aims to alleviate one or more problems of the prior art.The current invention offers a plant-based solution to reduce stress and promote serenity outside the brain, circumventing additive pathways. The invention provides one or more bioactive peptides that act as antagonists of the orexin receptors. The inhibition of these receptors decreases cortisol release and as such induces a state of relaxation enabling sleep.Summary of the inventionThe current inventors have found peptides that promote sleep in a subject. The peptides target orexin pathways and reduce peripheral cortisol concentrations by decreasing the concentration of peripheral cortisol released from the adrenal glands. By modulating the orexin signalling pathway and reducing circulating levels of cortisol, the current invention reduces stress, promotes relaxation and enables initiation of the natural sleep cycle and cellular restoration process, in a safe, non-addictive way.When tested in an in vitro setting with adrenal cortex cells, the peptides of the invention were shown to antagonise orexin signalling, which resulted in a significant absolute reduction in cortisol secretion by 17.4%, and a 44.3% decrease in induced cortisol (Figure 2 to 4).The peptides of the invention also have ancillary functionalities important to sleep, such as anti-inflammation effects and anti-anxiolytic effects. Therefore, the current invention has a multi-mechanistic approach to reducing stress and positively affecting sleep.An aspect of the current invention provides a peptide, typically up to 50 amino acids in length, comprising (or consisting of) an amino acid sequence selected from SEQUENCE ID NO. 1 to SEQUENCE ID NO. 5 and 97 to 100, or a variant of the amino acid sequence (herein after referred to as “peptide of the invention”).The peptides of the invention are derived from brown rice (Oryza sativa).The amino acid sequences of SEQUENCE ID NO. 1 to 6 and 97 to 100 are as follows:SEQUENCE ID NO. 1 : YYPGLSNSEQUENCE ID NO. 2: VSEWDPSKDKSEQUENCE ID NO. 3: QGLLVPRYSNTPGLVYSEQUENCE ID NO. 4: GATDVGHPMSEQUENCE ID NO. :5 FATPPVHGSOne example of a variant of SEQUENCE ID NO. 4 is SEQUENCE ID NO. 6.SEQUENCE ID NO. 6 has the following amino acid sequence.SEQUENCE ID NO. 6: ATDVGHPMSEQUENCE ID NO. 97 QLLSQSTSSEQUENCE ID NO. 98 QQQYYPGLSSEQUENCE ID NO. 99: LADTYNPRSEQUENCE ID NO. 100: IGGIGTVPVGRThe peptide of the invention is a sleep promoting peptide.In an embodiment, the peptide of the invention has anti-inflammatory activity.In an embodiment, the peptide of the invention has anti-anxiolytic activity.In an embodiment, the peptide of the invention is bioactive.In an embodiment, the peptide of the invention is a modified peptide. In an embodiment, the peptide is modified to increase its lipophilicity. In an embodiment, the peptide is modified to increase its half-life. In an embodiment, an N-terminal or C-terminal amino acid of the peptide is modified. In an embodiment, the peptide is modified with a protecting group. In one embodiment, the N-terminal or C-terminal amino acid of the peptide is modified with a protecting group.An aspect of the invention provides a conjugate comprising one or more peptides of the invention conjugated or linked, or fused, to a binding partner (herein referred to as “the conjugate of the invention”). In an embodiment, the peptide of the invention is modified with a reactive group or similar, configured to allow conjugation to the binding partner.An aspect of the invention provides a composition comprising one or more peptides of the invention (herein referred to as “the composition of the invention”). The composition of the invention may comprise at least 2 peptides of the invention, preferably 3 or more peptides of the invention, preferably 4 or more peptides of the invention, preferably 5 or more peptides of the invention.The composition of the invention may comprise a peptide comprising (or consisting of)SEQUENCE ID NO. 1 or a variant thereof, a peptide comprising (or consisting of)SEQUENCE ID NO. 2, or a variant thereof, a peptide comprising (or consisting of)SEQUENCE ID NO. 3, or a variant thereof, a peptide comprising (or consisting of)SEQUENCE ID NO. 4 or a variant thereof, a peptide comprising (or consisting of) SEQUENCE ID NO. 5, or a variant thereof, a peptide comprising (or consisting of) SEQUENCE ID NO. 97 or a variant thereof, a peptide comprising (or consisting of) SEQUENCE ID NO.98 or a variant thereof, a peptide comprising (or consisting of) SEQUENCE ID NO. 99 or a variant thereof, and / or a peptide comprising (or consisting of) SEQUENCE ID NO. 100 or a variant thereof.In an embodiment of the invention the composition comprises one or more peptides selected from a peptide comprising (or consisting of) a sequence selected from SEQUENCE ID NO. 1 to 5.In an embodiment of the invention the composition comprises one or more peptides selected from a peptide consisting of a sequence selected from SEQUENCE ID NO. 1 to 5 and 97 to 100.In an embodiment of the invention, the composition comprises all the peptides of the invention.In an embodiment, the composition of the invention is a powder. The powder is a food grade powder, i.e. , suitable for addition to food or feed products, or beverage products.In an embodiment, the composition of the invention is formulated as a capsule. In an embodiment, the capsule comprises the powder of the invention. The capsule is food grade, i.e. suitable for addition to food , beverage or feed products.In an embodiment, the powder comprises about 0.0001 to about 1.0%, about 0.0001 to about 0.2%, about 0.001 to about 0.1 %, or about 0.01 to about 0.1%, of the one or more peptides of the invention (w / w).In an embodiment the composition is edible (comestible). In one embodiment, the composition is a food or beverage. It is one suitable for human, animal (mammalian) or avian consumption, preferably for human consumption.In an embodiment, the composition is nutritional or dietary supplement.In an embodiment, the composition is a pharmaceutical composition, optionally comprising at least one pharmaceutically acceptable excipient.Preferably, the composition is man-made.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in promoting sleep in a subject. This can involve induction of sleep in a subject.As aspect of the invention provides a peptide of the invention or a composition of the invention for use in improving sleep in a subject.“Improving sleep” can include maintenance of sleep cycles, such as maintaining the appropriate length of time for a sleep cycle, including rapid eye movement (REM) and deep sleep.As aspect of the invention provides a peptide of the invention or a composition of the invention for use in inducing relaxation in a subject. This can include an induction of calmness in a subject.As aspect of the invention provides a peptide of the invention or a composition of the invention for use in reducing or preventing stress in a subject.An aspect of the invention provides the peptide of the invention or the composition of the invention for use in reducing cortisol in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in promoting recovery from fatigue in a subject. In an embodiment, recovery is post infection in the subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in reducing or preventing anxiety in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in treatment or prevention of inflammation in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in treatment or prevention of an inflammatory disorder in a subject.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in increasing focus in a subject, “focus” can include an increase in attention span in a subject and / or productivity.An aspect of the invention provides a peptide of the invention or a composition of the invention for use in improving cognitive function or abilities in a subject.An aspect of the invention provides a non-therapeutic method of treating or preventing inflammation in a subject, the method comprising administration of a peptide of the invention or a composition of the invention to the subject. Examples of non-therapeutic treatment of inflammation include use to relieve normal, non-pathological, inflammation.An aspect of the invention provides a non-therapeutic method of promoting or improving sleep in a subject, the method comprising administration of a peptide of the invention or a composition of the invention to the subject.In an aspect, the invention provides a nucleic acid encoding one or more peptides of the invention.In an aspect, the invention provides an expression vector comprising DNA encoding one or more peptides of the invention, in which the vector is configured for heterologous expression of the one or more peptide of the invention, in a host cell (hereafter “expression vector of the invention”).In an aspect, the invention provides a host cell, especially a bacterium or mammalian producer cell, engineered to heterologously express one or more peptides of the invention (hereafter “transformed cell of the invention”). In one embodiment, the transformed host cell comprises an expression vector on the invention.The invention also provides a method of producing one or more peptides of the invention of the invention, comprising the steps of providing a transformed cell of the invention, culturing the transformed host cell to effect heterologous expression of recombinant peptide of the invention by the host cell, and recovering the recombinant peptide of the invention.The invention also provides a method of engineering a cell for heterologous expression of one or more peptides of the invention, comprising the steps of transforming the cell with an expression vector of the invention, whereby the transformed cell is capable of heterologous expression of the one or more peptides of the invention.DefinitionsAll publications, patents, patent applications and other references mentioned herein are hereby incorporated by reference in their entireties for all purposes as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference and the content thereof recited in full.Where used herein and unless specifically indicated otherwise, the following terms are intended to have the following meanings in addition to any broader (or narrower) meanings the terms might enjoy in the art:Unless otherwise required by context, the use herein of the singular is to be read to include the plural and vice versa. The term “a” or “an” used in relation to an entity is to be read to refer to one or more of that entity. As such, the terms “a” (or “an”), “one or more,” and “at least one” are used interchangeably herein.As used herein, the term “comprise,” or variations thereof such as “comprises” or “comprising,” are to be read to indicate the inclusion of any recited integer (e.g. a feature, element, characteristic, property, method / process step or limitation) or group of integers (e.g. features, element, characteristics, properties, method / process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein the term “comprising” is inclusive or open-ended and does not exclude additional, unrecited integers or method / process steps.As used herein, the term “disease” is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is used broadly to encompass any disorder, illness, abnormality, pathology, sickness, condition or syndrome in which physiological function is impaired irrespective of the nature of the aetiology (or indeed whether the aetiological basis for the disease is established). It therefore encompasses conditions arising from infection, trauma, injury, surgery, radiological ablation, poisoning or nutritional deficiencies.As used herein, the term “treatment” or “treating” refers to an intervention (e.g., the administration of an agent to a subject) which cures, ameliorates or lessens the symptoms of a disease or removes (or lessens the impact of) its cause(s). In this case, the term is used synonymously with the term “therapy”. Can be manifested by a permanent or temporary improvement in the subject’s condition. In this context it includes limiting and / or reversing disease progression.As used herein the terms “prevention” or “preventing” refer to an intervention (e.g. the administration of an agent to a subject), which prevents or delays the onset or progression of a disease, or the severity of a disease, in a subject, or reduces (or eradicates) its incidence within a treated population.As used herein, a “therapeutically effective amount” or “effective amount”, as applied to a reference peptide or composition means an amount that can be administered to a subject without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio, but one that is sufficient to provide the desired effect, e.g. the treatment or prophylaxis manifested by a permanent or temporary improvement in the subject’s condition. The amount will vary from subject to subject, depending on the age and general condition of the individual, mode of administration and otherfactors. Thus, while it is not possible to specify an exact effective amount, those skilled in the art will be able to determine an appropriate "effective" amount in any individual case using routine experimentation and background general knowledge. A therapeutic result in this context includes eradication or lessening of symptoms, reduced pain or discomfort, prolonged survival, improved mobility and other markers of clinical improvement. A therapeutic result need not be a complete cure.The term “peptide” used herein refers to a polymer composed of up to 50 amino acid monomers typically via peptide bond linkage. The peptide may be 3 to 50 amino acids in length. The peptide may be 4 to 50 amino acids in length. The peptide may be 5 to 50 amino acids in length. . The peptide may be 6 to 50 amino acids in length. The peptide may be 7 to 50 amino acids in length. The peptide may be 8, 9 or 10 to 50 amino acids in length. The peptide may be up to 20 or 30 amino acids in length. Peptides (including fragments and variants thereof) of and for use in the invention may be generated wholly or partly by chemical synthesis or by expression from nucleic acid. For example, the peptides of and for use in the present invention can be readily prepared according to well-established, standard liquid or, preferably, solid-phase peptide synthesis methods known in the art (see, for example, J. M. Stewart and J. D. Young, Solid Phase Peptide Synthesis, 2ndedition, Pierce Chemical Company, Rockford, Illinois (1984), in M. Bodanzsky and A. Bodanzsky, The Practice of Peptide Synthesis, Springer Verlag, New York (1984). When necessary, any of the peptides employed in the invention can be chemically modified to increase their stability. Typically, the peptide is a linear peptide.A “chemically modified peptide” or a “peptide analog” includes any functional chemical equivalent of the peptide characterized by its increased stability and / or efficacy in vivo or in vitro in respect of the practice of the invention. The term peptide analog also refers to any amino acid derivative of a peptide as described herein. A peptide analog can be produced by procedures that include, but are not limited to, modifications to side chains, incorporation of unnatural amino acids and / or their derivatives during peptide synthesis and the use of crosslinkers and other methods that impose conformational constraint on the peptides or their analogs. Examples of side chain modifications include modification of amino groups, such as by reductive alkylation by reaction with an aldehyde followed by reduction with NaBF ; amidation with methylacetimidate; acetylation with acetic anhydride; carbamylation of amino groups with cyanate; trinitrobenzylation of amino groups with 2, 4, 6, trinitrobenzene sulfonic acid (TNBS); alkylation of amino groups with succinic anhydride and tetrahydrophthalic anhydride; and pyridoxylation of lysine with pyridoxa-5'-phosphate followed by reduction with NABH4. The guanidino group of arginine residues may be modified by the formation of heterocyclic condensation products with reagents such as 2,3-butanedione, phenylglyoxal andglyoxal. The carboxyl group may be modified by carbodiimide activation via o-acylisourea formation followed by subsequent derivatization, for example, to a corresponding amide. Sulfhydryl groups may be modified by methods, such as carboxymethylation with iodoacetic acid or iodoacetamide; performic acid oxidation to cysteic acid; formation of mixed disulphides with other thiol compounds; reaction with maleimide; maleic anhydride or other substituted maleimide; formation of mercurial derivatives using 4-chloromercuribenzoate, 4- chloromercuriphenylsulfonic acid, phenylmercury chloride, 2-chloromercuric-4-nitrophenol and other mercurials; carbamylation with cyanate at alkaline pH. Tryptophan residues may be modified by, for example, oxidation with N-bromosuccinimide or alkylation of the indole ring with 2-hydroxy-5-nitrobenzyl bromide or sulphonyl halides. Tryosine residues may be altered by nitration with tetranitromethane to form a 3-nitrotyrosine derivative. Modification of the imidazole ring of a histidine residue may be accomplished by alkylation with iodoacetic acid derivatives or N-carbethoxylation with diethylpyrocarbonate. Examples of incorporating unnatural amino acids and derivatives during peptide synthesis include, but are not limited to, use of norleucine, 4-amino butyric acid, 4-amino-3-hydroxy-5-phenylpentanoic acid, 6- aminohexanoic acid, t-butylglycine, norvaline, phenylglycine, ornithine, sarcosine, 4-amino-3- hydroxy-6-methylheptanoic acid, 2-thienyl alanine and / or D-isomers of amino acids. Peptide structure modification includes the generation of retro-inverso peptides comprising the reversed sequence encoded by D-amino acids.In this specification, the term “sequence identity” should be understood to mean the amount of nucleotides which match between different sequences. For example, a 16S rRNA gene sequence that shares at least 98% sequence identity with a reference sequence is one in which any 98% of aligned nucleotides of the variant are identical to the corresponding nucleotides in the reference sequence across the entire length of the sequence. Sequence identity is the amount of characters which match exactly between two different sequences. Hereby, gaps are not counted, and the measurement is relational to the shorter of the two sequencesThe term “variant” is a peptide that is substantially identical to the peptide of the invention, as defined herein, but altered in respect of one or more amino acid residues. Preferably such alterations involve the insertion, addition, deletion and / or substitution of 6 or fewer amino acids, preferably 5 or fewer, 4 or fewer, even more preferably of 3 or fewer, most preferably of 1 or 2 amino acids only. Insertion, addition, and substitution with natural and modified amino acids is envisaged. The variant may have conservative amino acid changes, wherein the amino acid being introduced is similar structurally, chemically, or functionally to that being substituted. The term “variant” is also intended to include chemical derivatives of the protein, i.e. , where one or more residues is chemically derivatized by reaction of a functional sidegroup. Also included are variants in which naturally occurring amino acid residues are replaced with amino acid analogues. Details of amino acid analogues are well known to those skilled in the art. The variant is one which maintains the activity of the peptide, such as sleep promoting activity.In an embodiment, the variant is a “therapeutically effective variant”. The term “therapeutically effective variant” as applied to a reference peptide means peptides having an amino acid sequence that is substantially identical to the reference peptide, and which is therapeutically effective as defined herein, such as sleep promoting activity, i.e., it is a sleep promoting variant. Thus, for example, the term should be taken to include variants that are altered in respect of one or more amino acid residues as disclosed above. Generally, the variant will have at least 50%, 60%, 70% amino acid sequence identity, preferably at least 80% sequence identity, more preferably at least 90% sequence identity, and ideally at least 95%, 96%, 97%, 98% or 99% sequence identity with the parent sequence. It should be noted that any variant will have principally the same therapeutic effect, or may have enhanced effect, when tested in in vitro or in vivo models of the disease.The term “variant” is also taken to encompass the term “fragment” and as such means a segment of a peptide of the invention. Typically, the fragment has between 3 to 15 contiguous amino acids in length. Typically, the fragment has between 4 to 12, or 5 to 10 contiguous amino acids in length. Generally, the fragment has a charge of about -1 to +1 at pH 7. The charge of a peptide, fragment or region is determined using the method of Cameselle, J.C., Ribeiro, J.M., and Sillero, A. (1986). Derivation and use of a formula to calculate the net charge of acid-base compounds. Its application to amino acids, proteins and nucleotides. Biochem. Educ. 14, 131-136.The term “subject” when used herein is any subject in need of treatment or prevention. It may be a mammal such as a human or animal. In an embodiment, it is a human subject.“Mammal” means a human or animal.When use herein the term “conjugate” refers to an embodiment of the invention in which the peptide is conjugated, linked or fused to a binding partner, for example one or more polyethylene glycol polymers or other compounds, such as molecular weight increasing compounds or lipophilic groups. The molecular weight increasing compound is any compound that will increase the molecular weight, typically by 10% to 90%, or 20% to 50% of the resulting conjugate and may have a molecular weight of between 200 and 20, 000, preferably between 500 and 10, 000. The molecular weight increasing compound may be PEG, any water-soluble (amphiphilic or hydrophilic) polymer moiety, homo or co-polymers of PEG, a monomethyl- subsitututed polymer of PEG (mPEG) and polyoxyethylene glycerol (POG), polyamino acidssuch as poly-lysine, poly-glutamic acid, poly-aspartic acid, particular those of L conformation, pharmacologically inactive proteins such as albumin, gelatin, a fatty acid, olysaccharide, a lipid amino acid and dextran. The polymer moiety may be straight chained or branched and it may have a molecular weight of 500 to 40000Da, 5000 to 10000 Da, 10000 to 5000, Da. The compound (binding partner) may be any suitable cell penetrating compound, such as tat peptide, penetratin, pep-1. The compound (binding partner) may be an antibody molecule. The compound (binding partner) may be a lipophilic moiety or a polymeric moiety. The lipophilic substituent and polymeric substituents are known in the art. The lipophilic substituent includes an acyl group, a sulphonyl group, an N atom, an O atom or an S atom which forms part of the ester, sulphonyl ester, thioester, amide or sulphonamide. The lipophilic moiety may include a hydrocarbon chain having 4 to 30 C atoms, preferably between 8 and 12 C atoms. It may be linear or branched, saturated or unsaturated. The hydrocarbon chain may be further substituted. It may be cycloalkane or heterocycloalkane. The peptide may be modified at the N-terminal, C-terminal or both. The polymer or compound (binding partner) is preferably linked to an amino, carboxyl or thio group and may be linked by N-termini or C-termini of side chains of any amino acid residue. The polymer or compound (binding partner) may be conjugated to the side chain of any suitable residue. The polymer or compound (binding partner) may be conjugated via a spacer. The spacer may be a natural or unnatural amino acid, succinic acid, lysyl, glutamyl, asparagyl, glycyl, beta-alanyl, gamma-amino butanoyl. The polymer or compound (binding partner) may be conjugated via an ester, a sulphonyl ester, a thioester, an amide, a carbamate, a urea, a sulphonamide. A person skilled in the art is aware of suitable means to prepare the described conjugate.In terms of “sequence homology”, the term should be understood to mean that a variant (or homolog) which shares a defined percent similarity or identity with a reference sequence when the percentage of aligned residues of the variant (or homolog) are either identical to, or conservative substitutions of, the corresponding residues in the reference sequence and where the variant (or homolog) shares the same function as the reference sequence.This alignment and the percent homology or sequence identity can be determined using software programs known in the art, for example, one alignment program is BLAST, using default parameters. Details of these programs can be found at the following Internet address: http: / / www.ncbi.nlm.nih.gov / blast / Blast.cgi.A variant (or homolog) that shares 70% sequence identity with a reference sequence is one in which any 70% of aligned residues of the variant (or homolog) are identical to, or conservative substitutions of, the corresponding residues in the reference sequence across the entire length of the sequence. Sequence identity is the amount of characters which matchexactly between two different sequences. Hereby, gaps are not counted and the measurement is relational to the shorter of the two sequences.The term “natural” as applied to a peptide means a peptide that includes (a) a fragment of a plant protein, typically flava bean protein, or variants of flava bean protein. The peptides or fragments of the invention may be isolated from plant proteins or made synthetically.“C-terminal domain” as applied to a fragment means the first three amino acids at the c- terminus of the fragment.“N-terminal domain” as applied to a fragment means the last three amino acids at the n- terminus of the fragment.The term “bioactive” as applied to a peptide or fragment means having a health promoting effect when administered a mammal, for sleep promoting activity.“Modified peptide”: In an embodiment of the invention the peptide is a modified peptide. The term modified peptide is used interchangeably with the term derivative of the peptide. The modified peptide includes a peptide which has been substituted with one or more groups as defined herein. The modification may be any modified that provides the peptides and or the composition of the invention with an increased ability to penetrate a cell. The modification may be any modification that increases the half-life of the composition or peptides of the invention. In one embodiment, the group is a protecting group. The protecting group may be an N- terminal protecting group, a C-terminal protecting group or a side-chain protecting group. The peptide may have one or more of these protecting groups. The person skilled in the art is aware of suitable techniques to react amino acids with these protecting groups. These groups can be added by preparation methods known in the art, for example the methods as outlined in paragraphs

[0104] to

[0107] of US2014120141. The groups may remain on the peptide or may be removed. The protecting group may be added during synthesis. In an embodiment of the invention the peptides may be substituted with a group selected from one or more straight chain or branched chain, long or short chain, saturated, or unsaturated, substituted with a hydroxyl, amino, amino acyl, sulfate or sulphide group or unsubstituted having from 1 to 29 carbon atoms. N-acyl derivatives include acyl groups derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isosteric acid, elaidoic acid, 2-ethylhexaneic acid, coconut oil fatty acid, tallow fatty acid, hardened tallow fatty acid, palm kernel fatty acid, lanolin fatty acid or similar acids. These may be substituted or unsubstituted. When substituted they are preferably substituted with hydroxyl, or sulphur containing groups such as but not limited to SO3H, SH, or S-S. In an embodiment of the current invention, the peptide is R1-X- R2. R1 and / or R2 groups respectively bound to the amino-terminal (N-terminal) and carboxyl-terminal(C-terminal) of the peptide sequence. In one embodiment, the peptide is Ri-X. Alternatively, the peptide is X- R2. Preferably, R1 is H, C1-4 alkyl, acetyl, benzoyl or trifluoroacetyl. X is the peptide of the invention; R2 is OH or NH2. In an embodiment, R 1 is selected from the group formed by H, a non-cyclic substituted or unsubstituted aliphatic group, substituted or unsubstituted al icyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, Tert- butyloxycarbonyl, 9-fluorenylmethyloxycarbonyl (Fmoc) and R5-CO-, wherein R5 is selected from the group formed by H, a non-cyclic substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroarylalkyl;R2 is selected from the group formed by -NR3R4, -OR3 and -SR3, wherein R3 and R4 are independently selected from the group formed by H, a non-cyclic substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and with the condition that R1 and R2 are not a-amino acids. In accordance with another preferred embodiment, R2 is -NR3R4, -OR 3 or -SR 3 wherein Rs and R4 are independently selected from the group formed by H, substituted or unsubstituted C 1-C 24 alkyl, substituted or unsubstituted C2-C 24 alkenyl, Tert-butyloxycarbonyl, 9- fluorenylmethyloxycarbonyl (Fmoc), substituted or unsubstituted C2-C 24 alkynyl, substituted or unsubstituted C3-C 24 cycloalkyl, substituted or unsubstituted C 5-C 24 cycloalkenyl, substituted or unsubstituted Cs-C 24 cycloalkynyl, substituted or unsubstituted C 6-C 30 aryl, substituted or unsubstituted C7-C24 aralkyl, substituted or unsubstituted heterocyclyl ring of 3- 10 members, and substituted or unsubstituted heteroarylalkyl of 2 to 24 carbon atoms and 1 to 3 atoms other than carbon wherein the alkyl chain is of 1 to 6 carbon atoms. Optionally, R 3 and R 4 can be bound by a saturated or unsaturated carbon-carbon bond, forming a cycle with the nitrogen atom. More preferably R 2 is -NR3R4 or -OR 3, wherein R3 and R4 are independently selected from the group formed by H, substituted or unsubstituted C1-C 24 alkyl, substituted or unsubstituted C2-C24 alkenyl, substituted or unsubstituted C2-C24 alkynyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted Ce-C 15 aryl and substituted or unsubstituted heterocyclyl of 3-10 members, substituted or unsubstituted heteroarylalkyl with a ring of 3 to 10 members and an alkyl chain of 1 to 6 carbon atoms. More preferably R3 and R4 are selected from the group formed by H, methyl, ethyl, hexyl, dodecyl, or hexadecyl. Even more preferably R3 is H and R4 is selected from the group formed by H, methyl, ethyl, hexyl, dodecyl, or hexadecyl. In accordance with an even more preferred embodiment, R2 is selected from -OH and -NH2. In accordance with another embodiment of this invention R 1 is selected from the group formed by H, acetyl, lauroyl, myristoyl or palmitoyl,and R2 is -NR3R 4 or -ORs wherein Rsand R4are independently selected from H, methyl, ethyl, hexyl, dodecyl and hexadecyl, preferably R2 is -OH or -NH2. More preferably, R1 is acetyl or palmitoyl and R2 is -NH2. In a preferred embodiment, the acyl group is bound to the N-terminal end of at least one amino acid of the peptide. In an embodiment of the invention, the peptide is modified to comprise a side chain protecting group. The side chain protecting group may be one or more of the groups comprising benzyl or benzyl based groups, t-butyl-based groups, benzyloxy-carbonyl (Z) group, and allyloxycarbonyl (alloc) protecting group. The side chain protecting group may be derived from an achiral amino acid such as achiral glycine. The use of an achiral amino acid helps to stabilise the resultant peptide and also facilitate the facile synthesis route of the present invention. Preferably, the peptide further comprises a modified C-terminus, preferably an amidated C-terminus. The achiral residue may be alphaaminoisobutyric acid (methylalaine). It will be appreciated that the specific side chain protecting groups used will depend on the sequence of the peptide and the type of N-terminal protecting group used.Man-made” as applied to comestible products should be understood to mean made by a human being and not existing in nature.“Dietary supplement” means a product that is suitable for mammalian ingestion as a means of supplementing the mammals’ primary dietIn this specification, the term “composition” should be understood to mean something made by the hand of man, and not excludes naturally occurring compositions. Exemplary compositions include foods, beverages, nutritional supplements, personal care compositions, and pharmaceutical compositions.“Pharmaceutical compositions”: A further aspect of the invention relates to a pharmaceutical composition comprising a peptide of the invention or a composition of peptides of the invention, admixed with one or more pharmaceutically acceptable excipients, including diluents and carriers. Even though the peptides and compositions of the present invention can be administered alone, they will generally be administered in admixture with a pharmaceutical excipient, particularly for human therapy. The pharmaceutical compositions may be for human or animal usage in human and veterinary medicine.In an embodiment of the invention the excipient may be a suitable diluent, carrier, binder, lubricant, suspending agent, coating agent, preservative, stabilisers, dyes, vehicle, solubilising agent, base, emollient, emulsifying agent, fragrance, humectant, and / or surfactants.Examples of such suitable excipients for the various different forms of pharmaceutical compositions described herein may be found in the “Handbook of Pharmaceutical Excipients,2ndEdition, (1994), Edited by A Wade and PJ Weller. In particular, formulations for topical delivery are described in Topical drug delivery formulations edited by David Osborne and Antonio Aman, Taylor & Francis, the complete contents of which are incorporated herein by reference.Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit. 1985).Examples of suitable diluents include, but are not limited to, any diluent disclosed in disclosed in US2014120131 or US2004132667. Examples include ethanol, glycerol and water.Examples of suitable carriers include, but are not limited to, lactose, starch, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol and the like and any suitable carrier disclosed in US2014120131 or US2004132667. In some embodiments, the carrier may include, but is not limited to, a liquid, such as water, oils or surfactants, including those of petroleum, animal, plant or synthetic origin, polymer, oil, such as peanut oil, mineral oil, castor oil, soybean oil, alcohol, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glycosides, maltosides, fatty alcohols, nonoxynols, poloxamers, polyoxyethylenes, polyethylene glycols, dextrose, glycerol, or digitonin. It will be understood that the carrier will be dermatologically acceptable. Preferred carriers contain an emulsion such as oil-in-water, water-in-oil, water-in-oil-in-water and oil-in-water-in-silicone emulsions. Emulsions may further contain an emulsifier and / or an anti-foaming agent.Examples of suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flow lactose, beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol and any suitable binder disclosed in US2014120131 or US2004132667.Examples of suitable lubricants include, but are not limited to, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, and sodium chloride and any suitable lubricant disclosed in US2014120131 or US2004132667.The choice of pharmaceutical excipient, including carriers or diluents, can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositions may comprise as, or in addition to, the excipient any suitable carrier(s), diluent(s), binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilising agent(s). Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flow lactose, beta-lactose, corn sweeteners, natural and syntheticgums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol. Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Preservatives, stabilizers, dyes and even flavouring agents may be provided in the pharmaceutical composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may be also used.Compositions may be formulated in unit dosage form, i.e., in the form of discrete portions containing a unit dose, or a multiple or sub-unit of a unit dose.A person of ordinary skill in the art can easily determine an appropriate dose of one of the instant compositions or peptides to administer to a subject without undue experimentation. Typically, a physician will determine the actual dosage which will be most suitable for an individual patient or subject and it will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual undergoing therapy. The dosages disclosed herein are exemplary of the average case. There can of course be individual instances where higher or lower dosage ranges are merited, and such are within the scope of this invention. Depending upon the need, the peptide / composition may optionally be administered at a dose of from 0.01 to 250 mg / kg body weight, It may be provided in one or more doses. In an embodiment, the does is 250, 500 or 1000mg per day regardless of body weight.“Feed grade” means the source is consumable and the enzymes used in the production of it are also safe to consume.As used herein, the term “expression vector of the invention” may be any suitable vector, including chromosomal, non-chromosomal, and synthetic nucleic acid vectors (a nucleic acid sequence comprising a suitable set of expression control elements) suitable for expression of a peptide of the invention in a cell. Examples of such vectors include derivatives of SV40, bacterial plasmids, phage DNA, baculovirus, yeast plasmids, vectors derived from combinations of plasmids and phage DNA, and viral nucleic acid (RNA or DNA) vectors. In one embodiment, the peptide-encoding nucleic acid molecule is comprised in a naked DNA or RNA vector, including, for example, a linear expression element (as described in, for instance, Sykes and Johnston, Nat Biotech 12, 355-59 (1997)), a compacted nucleic acid vector (as described in for instance U.S. Pat. No. 30 6,077,835 and / or WO 00 / 70087), or a plasmid vector such as pBR322, pUC 19 / 18, or pUC 118 / 119. Such nucleic acid vectors and the usage thereof are well known in the art (see, for instance, U.S. Pat. No. 5,589,466 andU.S. Pat. No. 5,973,972). In one embodiment, the DNA comprises an expression control sequence.In one embodiment, the vector is suitable for expression of the peptide of the invention in a bacterial cell. Examples of such vectors include expression vectors such as BlueScript (Stratagene), pIN vectors (Van Heeke & Schuster, 1989, J Biol Chem 264, 5503-5509), pET vectors (Novagen, Madison, Wis.) and the like. In one embodiment, the expression vector may also or alternatively be a vector suitable for expression in a yeast system. Any vector suitable for expression in a yeast system may be employed. Suitable vectors include, for example, vectors comprising constitutive or inducible promoters such as yeast alpha factor, alcohol oxidase and PGH (reviewed in: F. Ausubel et al., ed., 1987, Current Protocols in Molecular Biology, Greene Publishing and Wiley InterScience New York; and Grant et al., 1987, Methods in Enzymol 153, 516-544). In other embodiments, the expression vector is suitable for expression in baculovirus-infected insect cells. (Kost, T; and Condreay, J P, 1999, Current Opinion in Biotechnology 10 (5): 428-33.)Expression control sequences are engineered to control and drive the transcription of genes of interest, and subsequent expression of proteins in various cell systems. Plasmids combine an expressible gene of interest with expression control sequences (i.e. expression cassettes) that comprise desirable elements such as, for example, promoters, enhancers, selectable markers, operators, etc. In an expression vector of the invention, peptide encoding nucleic acid molecules may comprise or be associated with any suitable promoter, enhancer, selectable marker, operator, repressor protein, polyA termination 20 sequences and other expression-facilitating elements.“Promoter” as used herein indicates a DNA sequence sufficient to direct transcription of a DNA sequence to which it is operably linked, i.e., linked in such a way as to permit transcription of the peptide of the invention-encoding nucleotide sequence when the appropriate signals are present. The expression of a peptide-encoding nucleotide sequence may be placed under control of any promoter or enhancer element known in the art. Examples of such elements include strong expression promoters (e.g., human CM IE promoter / enhancer or CM major IE (CMV-MIE) promoter, as well as RSV, SV40 late promoter, SL3-3, MMTV, ubiquitin (Ubi), ubiquitin C (UbC), and HIV LTR promoters). In some embodiments, the vector comprises a promoter selected from the group consisting of SV40, CMV, CMV-IE, CMV-MIE, RSV, SL3-3, MMTV, Ubi, UbC and HIV LTR.Nucleic acid molecules of the invention may also be operably linked to an effective poly (A) termination sequence, an origin of replication for plasmid product in E. coli, an antibiotic resistance gene as selectable marker, and / or a convenient cloning site (e.g., a polylinker).Nucleic acids may also comprise a regulatable inducible promoter (inducible, repressable, developmentally regulated) as opposed to a constitutive promoter such as CMV IE (the skilled artisan will recognize that such terms are actually descriptors of a degree of gene expression under certain conditions).Selectable markers are elements well-known in the art. Under the selective conditions, only cells that express the appropriate selectable marker can survive. Commonly, selectable marker genes express proteins, usually enzymes, that confer resistance to various antibiotics in cell culture. In other selective conditions, cells that express a fluorescent protein marker are made visible, and are thus selectable. Embodiments include betalactamase (bla) (beta-lactam antibiotic resistance or ampicillin resistance gene or ampR), bls (blasticidin resistance acetyl transferase gene), bsd (blasticidin-S deaminase resistance gene), bsr (blasticidin-S resistance gene), Sh ble (Zeocin® resistance gene), hygromycin phosphotransferase (hpt) (hygromycin resistance gene), tetM (tetracycline resistance gene or tetR), neomycin phosphotransferase II (npt) (neomycin resistance gene or neoR), kanR (kanamycin resistance gene), and pac (puromycin resistance gene).In certain embodiments, the vector comprises one or more selectable marker genes selected from the group consisting of bla, bls, BSD, bsr, Sh ble, hpt, tetR, tetM, npt, kanR 20 and pac. In other embodiments, the vector comprises one or more selectable marker genes encoding green fluorescent protein (GFP), enhanced green fluorescent protein (eGFP), cyano fluorescent protein (CFP), enhanced cyano fluorescent protein (eCFP), or yellow fluorescent protein (YFP).For the purposes of this invention, gene expression in eukaryotic cells may be tightly regulated using a strong promoter that is controlled by an operatorthat is in turn regulated by a regulatory protein, which may be a recombinant “regulatory fusion protein” (RFP). The RFP consists essentially of a transcription blocking domain, and a ligand-binding domain that regulates its activity. Examples of such expression systems are described in US20090162901 A1 , which is herein incorporated by reference in its entirety.As used herein “operator” indicates a DNA sequence that is introduced in or near a gene in such a way that the gene may be regulated by the binding of the RFP to the operator and, as a result, prevents or allow transcription of the gene of interest, i.e. a nucleotide encoding a peptide of the invention. A number of operators in prokaryotic cells and bacteriophage have been well characterized (Neidhardt, ed., Escherichia coli and Salmonella; Cellular and Molecular Biology 2d. Vol 2 ASM Press, Washington D.C. 1996). These include, but are not limited to, the operator region of the LexA gene of E. coli, which binds the LexA peptide, and the lactose and tryptophan operators, which bind the repressor proteins encoded by the Ladand trpR genes of E. coli. These also include the bacteriophage operators from the lambda PR and the phage P22 ant / mnt genes, which bind the repressor proteins encoded by lambda cl and P22 arc. In some embodiments, when the transcription blocking domain of the RFP is a restriction enzyme, such as Notl, the operator is the recognition sequence for that enzyme. One skilled in the art will recognize that the operator must be located adjacent to, or 3' to the promoter such that it is capable of controlling transcription by the promoter. For example, U.S. Pat. No. 5,972,650, which is incorporated by reference herein, specifies that tetO sequences be within a specific distance from the TATA box. In specific embodiments, the operator is preferably placed immediately downstream of the promoter. In other embodiments, the operator is placed within 10 base pairs of the promoter. In an exemplary cell expression system, cells are engineered to express the tetracycline repressor protein (TetR) and a protein of interest is placed under transcriptional control of a promoter whose activity is regulated by TetR. Two tandem TetR operators (tetO) are placed immediately downstream of a CMV-MIE promoter / enhancer in the vector.Transcription of the gene encoding the protein of interest directed by the CMV-MIE promoter in such vector may be blocked by TetR in the absence of tetracycline or some other suitable inducer (e.g. doxycycline). In the presence of an inducer, TetR protein is incapable of binding tetO, hence transcription then translation (expression) of the protein of interest occurs. (See, e.g., U.S. Pat. No. 7,435,553, which is herein incorporated by reference in its entirety.)The vectors of the invention may also employ Cre-lox recombination tools to facilitate the integration of a gene of interest into a host genome. A Cre-lox strategy requires at least two components: 1) Cre recombinase, an enzyme that catalyzes recombination between two loxP sites; and 2) loxP sites (e.g. a specific 34-base pair by sequence consisting of an 8-bp core sequence, where recombination takes place, and two flanking 13-bp inverted repeats) or mutant lox sites. (See, e.g. Araki et al., 1995, PNAS 92:160-4; Nagy, A. et al., 2000, Genesis 26:99-109; Araki et al., 2002, Nuc Acids Res 30(19):e103; and US20100291626A1 , all of which are herein incorporated by reference). In another recombination strategy, yeast-derived FLP recombinase may be utilized with the consensus sequence FRT (see also, e.g. Dymecki, S. M., 1996, PNAS 93(12): 6191-6196).As used herein, the term “host cell” includes any cell that is suitable for expressing a recombinant nucleic acid sequence. Cells include those of prokaryotes and eukaryotes (single-cell or multiple-cell), bacterial cells (e.g., strains of E. coli, Bacillus spp., Streptomyces spp., etc.), mycobacteria cells, fungal cells, yeast cells (e.g. S. cerevisiae, S. pombe, P. partoris, P. methanolica, etc.), plant cells, insect cells (e.g. SF-9, SF-21 , baculovirus-infected insect cells, Trichoplusia ni, etc.), non-human animal cells, mammalian cells, human cells, orcell fusions such as, for example, hybridomas or quadromas. In certain embodiments, the cell is a human, monkey, ape, hamster, rat or mouse cell. In other embodiments, the cell is eukaryotic and is selected from the following cells: CHO (e.g. CHO K1 , DXB-11 CHO, Veggie- CHO), COS (e.g. COS-7), retinal cells, Vero, CV1 , kidney (e.g. HEK293, 293 EBNA, MSR 293, MDCK, HaK, BHK21), HeLa, HepG2, WI38, MRC 5, Colo25, HB 8065, HL-60, Jurkat, Daudi, A431 (epidermal), CV-1 , U937, 3T3, L cell, C127 cell, SP2 / 0, NS-0, MMT cell, tumor cell, and a cell line derived from an aforementioned cell. In some embodiments, the cell comprises one or more viral genes, e.g. a retinal cell that expresses a viral gene (e.g. a PER.C6® cell). In some embodiments, the cell is a CHO cell. In other embodiments, the cell is a CHO K1 cell.As used herein, the term “transformed cell of the invention” refers to a host cell comprising a nucleic acid stably integrated into the cellular genome that comprises a nucleotide sequence coding for expression of a peptide of the invention. In another embodiment, the present invention provides a cell comprising a non-integrated (i.e., episomal) nucleic acid, such as a plasmid, cosmid, phagemid, or linear expression element, which comprises a sequence coding for expression of a peptide of the invention. In other embodiments, the present invention provides a cell line produced by stably transfecting a host cell with a plasmid comprising an expression vector of the invention.As used herein, the term “engineered” as applied to a cell means genetically engineered using recombinant DNA technology, and generally involves the step of synthesis of a suitable expression vector (see above) and then transfecting the expression vector into a host cell (generally stable transfection).As used herein, the term “heterologous expression” refers to expression of a nucleic acid in a host cell that does not naturally have the nucleic acid. Insertion of the nucleic acid into the heterologous host is performed by recombinant DNA technology.“sleep promoting” when applied to a peptide (including variants and compositions comprising same), means a peptide that is capable of promoting sleep in a subject. In this context, the peptide is capable of reducing cortisol expression in cells compared with an untreated control as determined by the assays described herein.“improvements in sleep” may be shown by an increase in the length of sleep, a decrease in the time before sleep onset. It may be shown in a deeper, or undisturbed period of sleep.The term “anti-inflammatory” as applied to a peptide (including variants) means a peptide that is capable of modulating expression of one or more mediators of inflammatory response such as mediators selected from Macrophage migration inhibitory factor (MIF), VEGF, andOsteopontin, RANTES, and B cell activation factor (BAFF), in cells compared with untreated control as determined by the assays described herein. In particular the peptide can reduce the expression of one or more of Macrophage migration inhibitory factor (MIF), VEGF, and Osteopontin and / or increase expression of one or more of RANTES, and B cell activation factor (BAFF).“Inflammatory disorder” means an immune-mediated inflammatory condition that affects humans and is generally characterised by dysregulated expression of one or more cytokines. Examples of inflammatory disorders include skin inflammatory disorders, inflammatory disorders of the joints, inflammatory disorders of the cardiovascular system, certain autoimmune diseases, lung and airway inflammatory disorders, intestinal inflammatory disorders. Examples of skin inflammatory disorders include dermatitis, for example atopic dermatitis and contact dermatitis, acne vulgaris, and psoriasis. Examples of inflammatory disorders of the joints include rheumatoid arthritis. Examples of inflammatory disorders of the cardiovascular system are cardiovascular disease and atherosclerosis. Examples of autoimmune diseases include Type 1 diabetes, Graves disease, Guillain-Barre disease, Lupus, Psoriatic arthritis, and Ulcerative colitis. Examples of lung and airway inflammatory disorders include asthma, cystic fibrosis, COPD, emphysema, and acute respiratory distress syndrome. Examples of intestinal inflammatory disorders include colitis and inflammatory bowel disease. Other inflammatory disorders include cancer, hay fever, periodontitis, allergies, hypersensitivity, ischemia, depression, systemic diseases, post infection inflammation and bronchitis.Brief Description of the FiguresThe invention will be more clearly understood from the following description of an embodiment thereof, given by way of example only, with reference to the accompanying drawings, in which:Figure 1 : Illustration of absolute and relative cortisol reduction The difference between untreated cells and vehicle control (+ orexin A 1 pM) is used to determine the relative cortisol reduction, as cortisol found in untreated cells will be endogenous compared to the full stimulation of cortisol release by orexin A.Figure 2: Effect of Composition A on cortisol secretion. Composition A decreases cortisol release from H295R cells. Adrenal cortex cells remained untreated or were treated with Composition A (25 - 200 pg / mL), orexin inhibitor (Oxi; 10 pM) or forskolin (10 pM). Cells were stimulated with orexin A (1 pM) for 4 hours before cell supernatants were collected to determine cortisol concentrations using a cortisol ELISA kit. Significance was analysed using a one-way Anova with outliers removed; ** P<0.01 , ***P<0.001, **** P<0.00001. Data presented are the mean ± SEM in at least three independent assays.Composition A comprises peptide of SEQUENCE ID NO. 1 , peptide of SEQUENCE ID NO. 2, peptide of SEQUENCE ID NO. 3, peptide of SEQUENCE ID NO. 4 and peptide of SEQUENCE ID NO. 5.Figure 3: Effect of peptides of the invention on cortisol secretion. Peptides decreased orexin-induced cortisol release from H295R cells. Adrenal cortex cells remained untreated or were treated with peptides (25 & 250 pg / mL) A) SEQUENCE ID NO. 1 , B) SEQUENCE ID NO. 2, C) SEQUENCE ID NO. 3, D) SEQUENCE ID NO. 4 and E) SEQUENCE ID NO. 5, orexin inhibitor (Oxi; 10 pM) or forskolin (10 pM). Cells were stimulated with orexin A (1 pM) for 4 hours before cell supernatants were collected to determine cortisol concentrations using a cortisol ELISA kit. Significance was analysed using a one-way ANOVA; * P<0.05, ** P<0.01 , **** P<0.00001. Data presented are the mean ± SEM in at least three independent assays.Figure 4: Effect of peptide of SEQUENCE ID NO. 6 on cortisol secretion. The peptide decreased orexin-induced cortisol release from H295R cells. Adrenal cortex cells remained untreated or were treated with peptide (25 & 250 pg / mL) SEQUENCE ID NO. 6, orexin inhibitor (Oxi; 10 pM) or forskolin (10 pM). Cells were stimulated with orexin A (1 pM) for 4 hours before cell supernatants were collected to determine cortisol concentrations using a cortisol ELISA kit. Significance was analysed using a one-way ANOVA; * P<0.05, ** P<0.01 , **** P<0.00001. Data presented are the mean ± SEM in at least three independent assays.Figure 5: Composition A has no effect on cell viability. Adrenal cortex cells remained untreated or were treated with Composition A (25 - 200 pg / mL), orexin inhibitor (Oxi; 10 pM) or forskolin (10 pM) for 4-hours prior to testing in the MTT assay. Data presented are the mean ± SEM in at least three independent assays.Figure 6: MTT assay on adrenal cortex cells with bioactive peptides of the invention. The peptides are not toxic to H295R cells. Percentage viability of adrenal cortex cells following treatment with A) peptide of SEQUENCE ID NO. 1 , B) peptide of SEQUENCE ID NO. 2, C) peptide of SEQUENCE ID NO. 3, D) peptide of SEQUENCE ID NO. 4 & E) peptide of SEQUENCE ID NO. 5, at 25 - 250 pg / mL for 4-hours. Data presented are the mean ± SEM of at least three independent experiments.Figure 7: Proteome profiler cytokine array. Levels of cytokine response from untreated control THP1 cells are shown in blue. Cytokine levels from cells stimulated with LPS 100 ng / ml for 24 hours are shown in green and cytokine release from cells treated with Composition A 500 pg / ml for a for a further 24 hours prior to LPS stimulation are shown in yellow. Data plotted represents the mean pixel intensity from the dot plots analysed used Image J software.Figure 8: Effect of peptides of the invention on cortisol secretion. Peptides decreased orexin-induced cortisol release from H295R cells. Adrenal cortex cells remained untreated or were treated with peptides (25 & 250 pg / mL) A) SEQUENCE ID NO. 97, B) SEQUENCE ID NO. 98, C) SEQUENCE ID NO. 99 and D) SEQUENCE ID NO. 100, orexin inhibitor (Oxi; 10 M) or forskolin (10 pM). Cells were stimulated with orexin A (1 pM) for 4 hours before cell supernatants were collected to determine cortisol concentrations using a cortisol ELISA kit. Significance was analysed using a one-way ANOVA; * P<0.05, ** P<0.01 , **** p<0.00001. Data presented are the mean ± SEM in at least three independent assays.Detailed Description of the InventionThe current inventors have surprisingly found a number of peptides derived from brown rice (Oryza sativa) protein that have beneficial effects for sleep.The peptides of the invention are antagonists of the orexin 1 receptor (OX1 R) and orexin 2 receptor (OX2R). The effects of cortisol inhibition, induces a state of relaxation, conducive to sleep.The orexin neuropeptides and their receptors were discovered in 1998, by two different research groups while searching for new signalling molecules. These peptides were named orexin-A and orexin-B because they were originally thought to influence on appetite (the term orexin comes from “orex / s”, the Greek word for appetite). However, additional research has shown that although the orexin peptides have only a modest influence on appetite, their effects on arousal and sleep are profound (Scammell and Winrow, (2011) Annual review of pharmacology and toxicology, 51 , 243).The genes for, and structure of orexin are highly conserved across mammalian species, which suggest a strong evolutionary pressure that maintains the structures. In mammals, orexins (A or B) bind to two subtypes of G-protein-coupled receptors (GPCR), OX1 R and OX2R and, they are produced by neurons (orexin neurons) located primarily in the lateral hypothalamic area (LHA) (Soya and Sakurai, (2020) Brain Res. Mar 15; 1731 :146037). Orexin receptors are predominately found in the cerebral space, but they are also expressed on the adrenal glands, where cortisol is synthesised. By targeting this orexin-dependent release of cortisol, the peptides of the invention can decrease its concentration without having to target the central nervous system (CNS).Thus, notably, in an aspect of the invention, a composition is provided (composition of the invention) that comprises at least one peptide of the invention. In a preferred embodiment, the composition comprises two peptides of the invention. It may be a combination of any twopeptides of the invention. The composition may comprise three peptides, four peptides, or five peptides of the invention. The composition may comprise all peptides of the invention.The composition is used for promoting sleep in a subject.The composition of the invention may be used for non-therapeutic purposes. For example, a non-therapeutic method of promoting or improving sleep in a subject is provided, the method comprising administering the composition or peptides of the invention to the subject.A non-therapeutic method of inducing relaxation in a subject is provided, the method comprising administering the composition or peptides of the invention to the subject.A non-therapeutic method of reducing or preventing stress in a subject is provided, the method comprising administering the composition or peptides of the invention to the subject.A non-therapeutic method of reducing cortisol in a subject is provided, the method comprising administering the composition or peptides of the invention to the subject.A non-therapeutic method of promoting recovery from fatigue in a subject is provided, the method comprising administering the composition or peptides of the invention to the subject.A non-therapeutic method of promoting or improving sleep in a subject is provided, the method comprising administering the composition or peptides of the invention to the subject.The invention further provides a method for treatment or prevention of an inflammatory disorder in a subject, the method comprising administration of a peptide or composition of the invention to the subject.An aspect of the invention provides a non-therapeutic method for increasing focus in a subject, the method comprising administration of a peptide or composition of the invention to the subject.An aspect of the invention provides a non-therapeutic method for improving cognitive function or abilities in a subject, the method comprising administration of a peptide or composition of the invention to the subject. The subject may be one that is otherwise healthy but requires an improvement in cognitive function due to lifestyle, and / or age. In one example, the subject is in menopause or perimenopause.An aspect of the invention provides a method for improving cognitive function or abilities in a subject, the method comprising administration of a peptide or composition of the invention to the subject. The subject may be one with impaired cognitive function due to a disease or disorder that negatively affects cognition, such as dementia.The subject may be a mammal such as a human or animal. Notably, it is a human subject. It may be any human subject, of any age. It may be a subject with one or more diseases or conditions associated with a decrease in sleeping state, such as Dementia, Alzheimer’s Disease, anxiety, and depression.The subject may be one suffering from one or more sleep disorders. A sleep disorder includes but is not limited to insomnia, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnias, sleep-related movement disorders, and isolated symptoms.The subject may be one in an environment susceptible to stress, such as financial stress, work-related stress, social stress, education related stress, such as examination stress, family-related stress.The subject may be one in an environment susceptible to a lack of sufficient sleep due to lifestyle, ageing, or family circumstances.The subject may be an otherwise healthy individual, i.e. not suffering from one or more sleep disorders.The subject may be one with a chronic illness, characterised by low energy levels, or an individual who is otherwise healthy and free of chronic illness but has low energy due to age, trauma, surgery.In an embodiment of the invention, the peptide comprises from about 3 to 50 amino acids in length, about 7 to about 50 amino acids in length, preferably up to or about, 10, 15, 20, 25, 30, 35, 40, 45, or 49 amino acids in length, preferably up to or about 14, 15, 16, 17, 18, 19, or 20 amino acids in length. It may be up to 16, up to 20 or up to 30 amino acids in length.In an embodiment of the invention, the composition comprises (or consists of) a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 4 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5, a peptide comprising (or consisting of) SEQUENCE ID NO. 97, apeptide comprising (or consisting of) SEQUENCE ID NO. 98, a peptide comprising (or consisting of) SEQUENCE ID NO. 99, and a peptide comprising (or consisting of) SEQUENCE ID NO. 100.In an embodiment of the invention, the composition comprises (or consists of) a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 6 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment of the invention, the composition comprises (or consists of) a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2, a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 4, a peptide comprising (or consisting of) SEQUENCE ID NO. 5 and a peptide comprising (or consisting of) SEQUENCE ID NO. 6.In one embodiment, the peptide comprises (or consists of) a variant of SEQUENCE ID NO. 1 . This variant has a sequence having 1 to 5 amino acid changes compared to SEQUENCE ID NO: 1. In one embodiment, the variant has 1 to 4 amino acid changes compared to SEQUENCE ID NO: 1. In one embodiment, the variant has 1 to 3 amino acid changes compared to SEQUENCE ID NO: 1. In one embodiment, the variant has 1 to 2 amino acid changes compared to SEQUENCE ID NO: 1. In one embodiment, the amino acid change is a conservative amino acid change. In one embodiment, the amino acid change is an amino acid substitution. In one embodiment, the amino acid substitution is a conservative substitution. In one embodiment, the amino acid change is an amino acid addition. In one embodiment, the amino acid change is an amino acid deletion.In one embodiment, the peptide comprises (or consists of) a variant of SEQUENCE ID NO. 2. In one embodiment, the variant comprises a sequence having 1 to 5 amino acid changes compared to SEQUENCE ID NO: 2. In one embodiment, the variant has 1 to 4 amino acid changes compared to SEQUENCE ID NO: 2. In one embodiment, the variant has 1 to 3 amino acid changes compared to SEQUENCE ID NO: 2. In one embodiment, the variant has 1 to 2 amino acid changes compared to SEQUENCE ID NO: 2. In one embodiment, the amino acid change is a conservative amino acid change. In one embodiment, the amino acid change is an amino acid substitution. In one embodiment, the amino acid substitution is a conservative substitution. In one embodiment, the amino acid change is an amino acid addition. In one embodiment, the amino acid change is an amino acid deletion. 1In one embodiment, the peptide comprises (or consists of) a variant of SEQUENCE ID NO. 3. In one embodiment, the variant has a sequence having 1 to 5 amino acid changes compared to SEQUENCE ID NO: 3. In one embodiment, the variant has 1 to 4 amino acid changes compared to SEQUENCE ID NO: 3. In one embodiment, the variant has 1 to 3 amino acid changes compared to SEQUENCE ID NO: 3. In one embodiment, the variant has 1 to 2 amino acid changes compared to SEQUENCE ID NO: 3. In one embodiment, the amino acid change is a conservative amino acid change. In one embodiment, the amino acid change is an amino acid substitution. In one embodiment, the amino acid substitution is a conservative substitution. In one embodiment, the amino acid change is an amino acid addition. In one embodiment, the amino acid change is an amino acid deletion.In one embodiment, the peptide comprises (or consists of) a variant of SEQUENCE ID NO. 4. In one embodiment, the variant has a sequence having 1 to 5 amino acid changes compared to SEQUENCE ID NO: 4. In one embodiment, the variant has 1 to 4 amino acid changes compared to SEQUENCE ID NO: 4. In one embodiment, the variant has 1 to 3 amino acid changes compared to SEQUENCE ID NO: 4. In one embodiment, the variant has 1 to 2 amino acid changes compared to SEQUENCE ID NO: 4. In one embodiment, the amino acid change is a conservative amino acid change. In one embodiment, the amino acid change is an amino acid substitution. In one embodiment, the amino acid substitution is a conservative substitution. In one embodiment, the amino acid change is an amino acid addition. In one embodiment, the amino acid change is an amino acid deletion.In one embodiment, the peptide comprises (or consists of) a variant of SEQUENCE ID NO. 5. In one embodiment, the variant has a sequence having 1 to 5 amino acid changes compared to SEQUENCE ID NO: 5. In one embodiment, the variant has 1 to 4 amino acid changes compared to SEQUENCE ID NO: 5. In one embodiment, the variant has 1 to 3 amino acid changes compared to SEQUENCE ID NO: 5. In one embodiment, the variant has 1 to 2 amino acid changes compared to SEQUENCE ID NO: 5. In one embodiment, the amino acid change is a conservative amino acid change. In one embodiment, the amino acid change is an amino acid substitution. In one embodiment, the amino acid substitution is a conservative substitution. In one embodiment, the amino acid change is an amino acid addition. In one embodiment, the amino acid change is an amino acid deletion.In an embodiment, the peptide comprises (or consists of) a variant of any peptide of the invention. For example, a variant of the sequence selected from any one of SEQUENCE ID NO. 97 to SEQUENCE ID NO. 100. In one embodiment, the variant has 1 to 4 amino acid changes compared sequence. In one embodiment, the variant has 1 to 3 amino acid changes compared sequence. In one embodiment, the variant has 1 to 2 amino acid changescompared sequence. In one embodiment, the amino acid change is a conservative amino acid change. In one embodiment, the amino acid change is an amino acid substitution. In one embodiment, the amino acid substitution is a conservative substitution. In one embodiment, the amino acid change is an amino acid addition. In one embodiment, the amino acid change is an amino acid deletion.The change is selected independently. The change present may be the same at each changed position, or may be different.An example of a variant of SEQUENCE ID NO. 4 is an amino acid sequence of SEQUENCE ID NO. 6.Examples of variants of SEQUENCE ID NO. 1 with 1 amino acid change are in Table 1.Table 1 : SEQUENCE ID NO. 1 variants.Examples of variants of SEQUENCE ID NO. 1 with 2 amino acids changes are in Table 2.Table 2: SEQUENCE ID NO. 1 variants.Examples of variants of SEQUENCE ID NO. 2 with 1 amino acid change are in Table 3.VSEWDPSKDKYTable 3: SEQUENCE ID NO. 2 variants.Examples of variants of SEQUENCE ID NO. 2 with 2 amino acid changes are in Table 4.Examples of variants of SEQUENCE ID NO. 2 with 3 amino acid changes are in Table 5.Table 5: SEQUENCE ID NO. 2 variants.Examples of variants of SEQUENCE ID NO. 2 with 4 amino acid changes are in Table 6.Table 6: SEQUENCE ID NO. 2 variants.Examples of variants of SEQUENCE ID NO. 3 with 1 amino acid change are in Table 7.Examples of variants of SEQUENCE ID NO. 3 with 2 amino acid changes are in Table 8.Table 8: SEQUENCE ID NO. 3 variants.Examples of variants of SEQUENCE ID NO. 3 with 3 amino acid changes are in Table 9.Table 9: SEQUENCE ID NO. 3 variants.Examples of variants of SEQUENCE ID NO. 3 with 4 amino acid changes are in Table 10.Table 10: SEQUENCE ID NO. 3 variants.Examples of variants of SEQUENCE ID NO. 3 with 5 amino acids changes are in Table 11.Table 11 : SEQUENCE ID NO. 3 variants.Examples of variants of SEQUENCE ID NO. 4 with 1 amino acid change are in Table 12.Table 12: SEQUENCE ID NO. 4 variants.Examples of variants of SEQUENCE ID NO. 4 with 2 amino acid changes are in Table 13.Table 13: SEQUENCE ID NO. 4 variants.Examples of variants of SEQUENCE ID NO. 4 with 3 amino acid changes are in Table 14.Table 14: SEQUENCE ID NO. 4 variants.Examples of variants of SEQUENCE ID NO. 5 with 1 amino acid change are in Table 15.Table 15: SEQUENCE ID NO. 5 variants.Examples of variants of SEQUENCE ID NO. 5 with 2 amino acid changes are in Table 16.Table 16: SEQUENCE ID NO. 5 variants.Examples of variants of SEQUENCE ID NO. 5 with 3 amino acid changes are in Table 17.Table 17: SEQUENCE ID NO. 5 variants.Variants of SEQUENCE ID NO. 97 include:QLLSQST (SEQUENCE ID NO. 101) QLLSQSTSQW(SEQUENCE ID NQ.102) QLLSQSTSQ(SEQUENCE ID NO. 103)Variants of SEQUENCE ID NO. 98 include:QQQYYPGFSN(SEQUENCE ID NO.104) QQQYYPGLSN (SEQUENCE ID NO.105) FQQQYYPGL (SEQUENCE ID NQ.106) QQYYPGLS (SEQUENCE ID NO. 107) FQQQYYPGLS (SEQUENCE ID NQ.108) QQQYYPGLSNE (SEQUENCE ID NO. 109) FQQQYYPGLSN (SEQUENCE ID NQ.110) QQYYPGLSN (SEQUENCE ID NO.111) QQQYYPGL (SEQUENCE ID NO.112) QQYYPGLSNE (SEQUENCE ID NO.113)Variants of SEQUENCE ID NO. 99 include:ADTYNPRA (SEQUENCE ID NO. 114) LADTYNPRA (SEQUENCE ID NO. 115) PNLADTYNPR (SEQUENCE ID NO.116) NLADTYNPRA (SEQUENCE ID NO. 117) LADTYNP (SEQUENCE ID NO. 118) ADTYNPR (SEQUENCE ID NO. 119) LADTYNPRAG (SEQUENCE ID NO. 120) RADTYNPR (SEQUENCE ID NO.121) NLADTYNPR (SEQUENCE ID NO.122)HADTYNPR (SEQUENCE ID NO. 123)Variants of SEQUENCE ID NO. 100 include:IGGIGTVPVGRV (SEQUENCE ID NO. 124)YKIGGIGTVPV (SEQUENCE ID NO. 125)IGGVGTVPVGK (SEQUENCE ID NO.126)KIGGIGTVPV (SEQUENCE ID NO. 127)IGGIGTVPV (SEQUENCE ID NO. 128)GIGTVPVGRV (SEQUENCE ID NO.129)GGIGTVPVGR (SEQUENCE ID NO. 130)IGGIGTVPVGRVE (SEQUENCE ID NO. 131)YKIGGIGTVPVGR (SEQUENCE ID NO. 132)GIGTVPVGRVE (SEQUENCE ID NO. 133)KIGGIGTVPVGR (SEQUENCE ID NO. 134)IGGIGTVPVG (SEQUENCE ID NO.135)KIGGIGTVPVG (SEQUENCE ID NO. 136)YKIGGIGTVPVG (SEQUENCE ID NO.137)GIGTVPVGR (SEQUENCE ID NO. 138)GGIGTVPVGRVE (SEQUENCE ID NO. 139)In an embodiment, the composition comprises substantially all the peptides of the invention. In one embodiment, the composition comprises substantially all the variants of the invention. In one embodiment, the composition is substantially free of other peptides.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 and a peptide comprising (or consisting of) SEQUENCE ID NO. 2. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 and a peptide comprising (or consisting of) SEQUENCE ID NO. 3. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 and a peptide comprising (or consisting of) SEQUENCE ID NO. 4. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 2 and a peptide comprising (or consisting of) SEQUENCE ID NO. 3. In an embodiment, the composition comprises a peptide comprising (or consisting of)SEQUENCE ID NO. 2 and a peptide comprising (or consisting of) SEQUENCE ID NO. 4. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 2 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 3 and a peptide comprising (or consisting of) SEQUENCE ID NO. 4. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 3 and a peptide comprising (or consisting of) SEQUENCE ID NO.5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 4 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2 and a peptide comprising (or consisting of) SEQUENCE ID NO. 3. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2 and a peptide comprising (or consisting of) SEQUENCE ID NO. 4. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 3 and a peptide comprising (or consisting of) SEQUENCE ID NO. 4. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 3 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 4, and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 2, a peptide comprising (or consisting of) SEQUENCE ID NO. 3 and a peptide comprising (or consisting of) SEQUENCE ID NO. 4. In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 2, a peptide comprising (or consisting of) SEQUENCE ID NO. 3 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 2, a peptide comprising (or consisting of) SEQUENCE ID NO. 4 and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 3, a peptide comprising (or consisting of) SEQUENCE ID NO. 4 and a peptide comprising (or consisting of) SEQUENCE ID NO.5.In an embodiment, the composition comprises a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 2 , a peptide comprising (or consisting of) SEQUENCE ID NO. 3, and a peptide comprising (or consisting of) SEQUENCE ID NO. 5.In an embodiment, the composition comprises one or more peptides selected from a peptide comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 3 and a peptide comprising (or consisting of) SEQUENCE ID NO. 100.In an embodiment, the composition comprises a peptides comprising (or consisting of) SEQUENCE ID NO. 1 , a peptide comprising (or consisting of) SEQUENCE ID NO. 3 and a peptide comprising (or consisting of) SEQUENCE ID NO. 100.In each of these embodiments, the peptide may comprise a variant of the sequence.It will be appreciated that the composition may comprise any combination of the peptides of the invention.In an embodiment, the composition comprises one or more peptides selected from a peptide comprising (or consisting of) a sequence selected from SEQUENCE ID NO. 1 to SEQUENCE ID NO. 100. In an embodiment the composition comprising all peptides selected from a peptide comprising (or consisting of) a sequence selected from SEQUENCE ID NO. 1 to SEQUENCE ID NO. 100.Preferably, the compositions may be for oral administration. For example, as a dietary supplement or a nutritional supplement. It will be appreciated that it may be in any suitable form.The peptides of the invention may be used in supplement or a pharmaceutical product to promote sleep.A peptide or a composition of the invention may be adapted for topical, oral, rectal, parenteral, intramuscular, intraperitoneal, intra-arterial, intrabronchial, subcutaneous, intradermal, intravenous, nasal, vaginal, buccal or sublingual routes of administration. The composition ofthe invention may be presented, prepared and / or administered in a variety of suitable forms. Such forms include, for example, but are not limited to, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, emulsions, microemulsions, tablets, pills, powders, liposomes, dendrimers and other nanoparticles, microparticles, capsules, suppositories and pressed into tablet form. It will be appreciated that the form may depend on the intended mode of administration, the nature of the composition or combination, and therapeutic application or other intended use. Formulations also can include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles, DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions, carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax.In some embodiments of the current invention, the composition may be delivered via any one of liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, millicapsules, capsules, macrocapsules, nanocapsules, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, mixed micelles of surfactants, surfactant-phospholipid mixed micelles, millispheres, spheres, lipospheres, particles, nanospheres, nanoparticles, milliparticles, solid nanopartciles as well as microemulsions including water-in-oil microemulsions with an internal structure of reverse micelle and nanoemulsions microspheres, microparticles.A variety of methods are available for preparing liposomes. See, e.g., Szoka et al., Ann. Rev. Biophys. Bioeng. 9:467 (1980), U.S. Pat. Nos. 4,186,183, 4,217,344, 4,235,871 , 4,261 ,975, 4,485,054, 4,501 ,728, 4,774,085, 4,837,028, 4,235,871 , 4,261 ,975, 4,485,054, 4,501 ,728, 4,774,085, 4,837,028, 4,946,787, PCT Publication No. WO 91 / 17424, Deamer & Bangham, Biochim. Biophys. Acta 443:629-634 (1976); Fraley, et al., PNAS 76:3348-3352 (1979); Hope et al., Biochim. Biophys. Acta 812:55-65 (1985); Mayer et al., Biochim. Biophys. Acta 858:161- 168 (1986); Williams et al., PNAS 85:242-246 (1988); Liposomes (Ostro (ed.), 1983, Chapter 1); Hope et al., Chem. Phys. Lip. 40:89 (1986); Gregoriadis, Liposome Technology (1984) and Lasic, Liposomes: from Physics to Applications (1993)). Suitable methods include, for example, sonication, extrusion, high pressure / homogenization, microfluidization, detergent dialysis, calcium-induced fusion of small liposome vehicles and ether fusion methods, all of which are well known in the art.These delivery systems may be adapted to achieve a greater penetration of the compound and / or peptides of the invention. This may improve pharmacokinetic and pharmacodynamics properties. The delivery system may be a sustained release system wherein the compound or peptide of the invention is gradually released during a period of time and preferably with a constant release rate over a period of time. The delivery systems are prepared by methodsknown in the art. The amount of peptide contained in the sustained release system will depend on where the composition is to be delivered and the duration of the release as well as the type of the condition, disease and / or disorder to be treated or cared for.In an embodiment of the invention the composition may further comprise at least one pharmaceutically acceptable excipient. Excipient may be used interchangeably with functional ingredient or additive. It will be understood that although a peptide or a composition of the current invention can be administered alone, they will generally be administered in admixture with a pharmaceutical excipient. Pharmaceutically acceptable excipient are well known in the art and any known excipient. Examples of suitable excipients are disclosed herein.Preferably any excipient included is present in trace amounts. The amount of excipient included will depend on numerous factors, including the type of excipient used, the nature of the excipient, the amount of active or peptide in the composition and / or the intended use of the composition. The nature and amount of any excipient should not unacceptably alter the benefits of the peptides of this invention.In an embodiment of the invention, the composition may further comprise one or more additional ingredients. The composition of the invention may be administered consecutively, simultaneously or sequentially with the one or more other additional agents. Such additional ingredients may be those of benefit to include in a composition formulated in a particular way, e.g. for oral administration, or of benefit depending on the intended use of the composition, e.g. sleep promotion. The additional ingredient may be active or functional or both.Advantageously, a peptide or composition may be used as a sole means of promoting and supporting restful sleep or may be used in combination with other similarly-directed compositions or agents, or as a component of a larger composition.In a particular embodiment, a peptide or composition is to be administered in combination with one or more other active agents, for example, existing anti-inflammatory agents, existing sleep promoting agents, or pharmacological enhancers available on the market. In such cases, the peptide(s) or composition of the invention may be administered consecutively, simultaneously, or sequentially with the one or more other active agents.It will be appreciated that a plurality of additional ingredients may be added. The amount of the additional ingredient may be from about 0.001% to about 50% weight of the composition, preferably, about 0.01% to about 20%, preferably about 0.1 % to about 10%, about 0.5% to about 10%, about 1% to about 5%, preferably 2% weight of the composition. The amount of additional ingredient included will depend on numerous factors, including the type of additional ingredient used, the nature of the additional ingredient, the component(s) of the composition,the amount of active or peptide in the composition and / or the intended use of the composition. The nature and amount of any additional ingredient should not unacceptably alter the benefits of the peptides of this invention.The composition of the invention may be alcohol free.The peptides of the invention are used in the composition of this invention at therapeutically effective concentrations to achieve the desired effect; in a preferred form with regards to the total weight of the composition, between 0.00000001% (in weight) and 20% (in weight); preferably between 0.000001% (in weight) and 15% (in weight), more preferably between 0.0001 % (in weight) and 10% (in weight) and even more preferably between 0.0001% (in weight) and 5% (in weight). Ideally, the peptides of the present invention are preferably used from about 0.00001% w / w to about 0.5% w / w [0.1 to 5000 ppm], and more preferably from 0.00005 w / w to about 0.05 w / w [0.5 to 500 ppm], and most preferably from about 0.0001 w / w to about 0.01 w / w of the composition [1 to 100 ppm]. Ideally, the peptides of the present invention are preferably used from about 0.0001% w / w to about 0.004% w / w of the composition.It is to be understood that an ingredient that is considered to be an “active” ingredient in one product may be a “functional” or “excipient” ingredient in another and vice versa. It will also be appreciated that some ingredients play a dual role as both an active ingredient and as a functional or excipient ingredient.In preferred embodiments, repeated use of the peptide(s) or composition is provided.The invention also comprises a food product comprising a peptides of the invention, or a composition of the invention. In a preferred embodiment, the food product is for human consumption.The composition of the invention may be a food product.In one embodiment the comestible product is a beverage. In one embodiment the comestible product is a bakery product. In one embodiment the comestible product is a dairy product. In one embodiment the comestible product is a snack product. In one embodiment the comestible product is a baked extruded food product. In one embodiment the comestible product is powdered milk. In one embodiment the comestible product is an infant formula product. In one embodiment the comestible product is a confectionary product. In one embodiment the comestible product is a yoghurt. In one embodiment the m comestible product is a yoghurt drink. In one embodiment the comestible product is an ice cream product. In one embodiment the comestible product is a frozen food product. In one embodiment the comestible product is a breakfast cereal. In one embodiment the comestible product is abread. In one embodiment the comestible product is a flavoured milk drink. In one embodiment the comestible product is a confectionary bar. In one embodiment the comestible product is a tea or tea product. In one embodiment the comestible product is a based extruded snack product. In one embodiment the comestible product is a fried snack product. In one embodiment the comestible product is a nutritional supplement. In one embodiment the comestible product is a sports nutritional product. In one embodiment the comestible product is a baby food product. In one embodiment the comestible product is a speciality food product for immunocompromised individuals. In one embodiment the comestible product is a food for geriatric patients.In one embodiment, the composition comprises 0.001 to 1.0% of the food product (w / w). In one embodiment, the composition comprises 0.005 to 0.5% of the food product (w / w). In one embodiment, the composition comprises 0.005 to 0.1 % of the food product (w / w). In one embodiment, the composition comprises 0.01 to 0.03% of the food product (w / w). In one embodiment, the composition comprises about 0.02% of the food product (w / w).The composition may be provided in a solid dosage form with specific controlled release characteristics. It may be layered dosage form, with each layer having unique release or dissolution characteristics.The invention will now be described with reference to specific Examples. These are merely exemplary and for illustrative purposes only: they are not intended to be limiting in any way to the scope of the monopoly claimed or to the invention described. These examples constitute the best mode currently contemplated for practicing the invention.EXAMPLESPeptides and Compositions usedPeptides used are a peptide of: SEQUENCE ID NO. 1 , SEQUENCE ID NO. 2, SEQUENCE ID NO. 3, SEQUENCE ID NO. 4, SEQUENCE ID NO. 5, SEQUENCE ID NO. 6, . SEQUENCE ID NO. 97, SEQUENCE ID NO. 98, SEQUENCE ID NO. 99, and SEQUENCE ID NO. 100.Composition A is a combination of SEQUENCE ID NO. 1 , SEQUENCE ID NO. 2, SEQUENCE ID NO. 3, SEQUENCE ID NO. 4, SEQUENCE ID NO. 5.Peptide CharacterisationMass Spectrometry AnalysisSample volume containing 5 mg of peptides was acidified with 0.2% formic acid (Sigma- Aldrich, St. Louis, MO, USA), desalted and concentrated using Oasis HLB prime SPE cartridges (Waters Corporation, Milford, MA, USA). Eluates were lyophilized and resuspendedin 100 pL Optima grade LC / MS water (Fisherbrand, Thermo Fisher Scientific Inc., Canoga Park, CA, USA). Peptide content is determined using BCA assay. Aliquot containing 20 pg is resuspended in 0.1 % TFA (Sigma-Aldrich, St. Louis, MO, USA), containing Pierce™ Peptide Retention Time Calibration Mixture, to the final concentration of 1 mg / mL (ThermoFisher Scientific Inc., Canoga Park, CA, USA).Samples were analysed by nano LC-MS / MS Dionex UltiMate 3000 coupled to a ThermoFisher Q Exactive (ThermoFisher Scientific Inc., Canoga Park, CA, USA) in positive polarity mode. Peptides were loaded on a trapping column and eluted over a 25 cm analytical column PepMap RSLC C18 (ThermoFisher Scientific Inc., Canoga Park, CA, USA) with a 1 h gradient at a flow rate of 300 nL / min. The mass spectrometer was operated in data-dependent mode, with MS and MS / MS performed in the Orbitrap at 70,000 FWHM and 17,500 FWHM resolution, respectively. From the MS scan, the fifteen most intense ions were selected for MS / MS.H295R Cell CultureAdrenal cortex cells, NCI-H295R [H295R] (American Type Culture Collection, ATCC-CRL- 2128™, Rockville, MD) were maintained, according to manufacturer guidelines, in culture using Gibco Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 (DMEM / F-12) (ThermoFisher Scientific) supplemented with 1% ITS+ Premix from Corning (Catalog No. 354352), 2.5% Nu-Serum from Corning (Catalog No. 355100) and 1% penicillin-streptomycin. Cells were kept viable at 37°C and 5% CO2.Cortisol ELISAH295R cells (300,000 cells / mL) were seeded in 24-well plates for 72 hours. After this time, non-attached cells were aspirated, and adherent cells were serum starved for a further 24 hours. After starvation, cells were treated with relevant assay controls and the peptide or composition (3.25 - 200 pg / mL) or remained untreated.A series of assay controls were used to validate the assay. Cells were stimulated to release cortisol using 1 pM orexin A (OxA; natural ligand of orexin receptor; 06012) (Sigma) or 10 pM Forskolin (F6886) (Sigma), while an orexin inhibitor (Oxi) SB-334867 (SML1530) (Sigma) at 10 pM was used to inhibit cortisol release (assay control only, commercially unavailable). All peptide and NPN treatments were made in serum free media containing 1 pM orexin A. Cells were treated for 4 hours before cell supernatants were collected to determine cortisol concentrations using a commercially available ELISA kit following the manufacturer’s instructions (Cortisol ELISA kit, ab154996, Abeam). Absorbance was measured at 450 nmwith a microplate spectrophotometer (CLARIOstar BMGlabtech). Data was expressed as inhibition of the orexin-induced concentration of cortisol.Toxicity AssayAn MTT assay was used to determine whether the peptides were toxic to cells upon treatment. H295R cells were seeded in 24 well plates (150,000 cells / well) and treated with Composition A (100 - 200 pg / mL). H295R cells were treated for 4 hours before the well contents were removed and replaced with MTT reagent (0.5 mg / mL). The cells were treated with an MTT reagent for 2 hours at 37°C, 95% humidity and 5% CO2. MTT reagent was removed from the cells and replaced with 100% DMSO for 5 mins while shaken on a plate shaker. The plate was read using a CLARIOstar BMG Labtech plate reader at 570 nm. The generated optical density values were converted to % with untreated cells set at 100%.Visualisation and StatisticsAll graphs and statistical analyses were performed using GraphPad Prism version 9.3.1 for Windows, GraphPad Software, San Diego, California USA. All treatment groups were normalised to vehicle controls, all of which were treated with orexin A. Significant differences between treatment groups and vehicle controls were determined by one-way ANOVA followed by a Dunnett's test or a Kruskal-Wallis test followed by a Dunn’s test, where appropriate. Relevant analysis is indicated in figure legends. Data is presented as a percentage of untreated controls (mean ± SEM of at least 3 independent experiments unless otherwise indicated). For all analyses, a P value <0.05 was considered significant. Peptide effect on cortisol secretion is calculated as absolute cortisol reduction (the amount of cortisol % reduction compared to vehicle control) or as a % of relative cortisol reduction (Figure 1). Here, the difference in cortisol secretion between untreated and vehicle controls is known as the relative cortisol reduction and is representative of the maximum amount of cortisol reduction required, and at which released cortisol would return to basal levels.Pre-clinical stability studiesSimulated in vitro Peptide StabilityFor key components of functional ingredients to modulate physiological pathways downstream they must survive gut transit and depending on their target, they may need to be absorbed through the intestinal barrier. By not only identifying active components of functional ingredients but also subsequently assessing their efficacy, bioavailability and stability may be key to enhancing the adoption of functional ingredients as both prevention and interventionnutritional strategies. The characterisation of the peptide of the invention is performed by identifying constituent active molecules, subsequently validating efficacy, assessing bioavailability and stability in a biological matrix. In this experiment, the inventors have synthetically reproduced and validated the effects of bioactive peptides of the invention. The bioaccessibility and bioavailability of the peptides has been measured by mimicking the upper gut transit and assessing the predicted peptide's ability to be transported across the intestinal barrier in-vitro.Anti-inflammatory StudiesCytokine ArrayA Proteome Profiler Human XL Cytokine Array kit (R&D Systems), containing four pre-coated nitrocellulose membranes with 105 duplicated cytokine and chemokine markers was employed to identify a variety of inflammatory cytokines that may be secreted in response Composition A on THP-1 cells. Supernatants was harvested from THP-1 cells and added to pre-coated and pre-blocked nitrocellulose blots for 1 hr, including 15 pL of detection antibody, and incubated at 4°C on a rocking platform overnight. The membranes were then washed thrice with 1x wash buffer before the addition of HRP solution for 30 mins at room temperature. The blots were re-washed and blotted dry before examination with chemiluminescent reagents for imaging in the G-Box. Densitometry analysis was used to evaluate cytokine expression release. Three pairs of reference markers spotted on the nitrocellulose blots confirm assay validity. The data were presented as percentage (%) area in terms of pixilation.RESULTSCharacterisationTable 18 below illustrates the results of characterisation of the peptides.Table 18: Peptide Characterisation. This table shows the sequences, length, molecular weight and charge of the peptides of the invention.Pre- & Non-clinical StudiesIn-vitro Data Analysis and ResultsAntagonised orexin signalling pathway and reduced cortisol secretionComposition A exhibited a dose-response of cortisol release, treatment with 200 pg / mL induced the greatest effect with an absolute reduction of 17.4% and a 44.3% induced reduction measured (Figure 2). Orexin A is a natural ligand and agonist of the orexin signalling pathway, as such, it was used as a vehicle control for all samples tested, except untreated, enabling a clear distinction between unstimulated and stimulated cells. Two additional assay controls were used to validate the assay, an orexin inhibitor (Oxi; 10 pM) as a positive control for inhibition and forskolin (10 pM) as a control for activation. Oxi inhibited cortisol below that observed endogenously, so was inhibiting non-orexin-induced cortisol also. However, as it was also potently inhibiting orexin-induced cortisol, it was deemed as an appropriate control (Figure 2). A sample that can modulate cortisol to endogenous concentrations in the presence of the orexin ligand was considered a positive result, which is one of the reasonings for calculating induced cortisol release as well as absolute. Forskolin was used to validate cortisol release from the adrenal cell line used for testing.While Composition A is a matrix of peptides, the activity of peptides predicted to elicit the anti- orexin activity was characterised. The peptides were synthesised synthetically and tested for cortisol modulation in H295R cells.Five peptides that were synthesised and tested in vitro were shown to have activity. Following a 4-hour incubation, SEQUENCE ID NO. 1 (Figure 3A), SEQUENCE ID NO. 2 ( (Figure 3B), SEQUENCE ID NO. 3 (Figure 3C) and SEQUENCE ID NO. 4 (Figure 3D) significantly inhibited cortisol release at 250 ug / mL (* P<0.05) with absolute reductions of 14%, 10%, 19% and 8% being recorded respectively. This equates to a 30%, 21 % 54% and 17% relative reduction to endogenous cortisol secretion. However, SEQUNCE ID NO. 4 (Figure 3D) and SEQUENCE ID NO. 5 (Figure 3E) significantly inhibited cortisol release at the lower concentration of 25 ug / mL with absolute reductions of 17% and 13% being recorded respectively, equating to 36% and 27% relative reductions. The absolute reduction observed with individual peptides is less than Composition A and at much higher concentrations. This suggests that peptides are likely to have synergistic or additive effects when combined.Four additional peptides were tested in vitro and also shown to have activity. See Figure 8(A) to (D) for a peptide of SEQUENCE ID NO. 97, SEQUENCE ID NO.98, SEQUENCE ID NO. 9, and SEQUENCE ID NQ.100. In Figure 8 A and B, SEQUENCE ID NO. 97 and SEQUENCE ID NO. 98 ) significantly inhibited cortisol release at 25 (* P<0.05; *** P<0.001 , respectively) and 250 ug / mL (**** P0.00001 , respectively). In Figure 8 C, SEQUENCE ID NO. 99 significantly inhibited cortisol release at 250 ug / mL (* P<0.05). In Figure 8 D, SEQUENCE ID NO. 100 significantly inhibited cortisol release at 25 ug / mL (* P<0.05). These results suggest that these peptides contribute to the effect on cortisol production seen with Composition A application.Composition A and cellular viabilityThe viability of adrenal cortex cells was not affected after 4-hours treatment with orexin inhibitor (Oxi; 10 pM), forskolin (10 pM) or Composition A (25 - 200 pg / mL) in an MTT assay (Figure 5, Figure 6). Untreated cells are considered 100% viable, therefore the effects on cellular viability in the treated cells were calculated as a percent of the untreated control cells. This data suggests that Composition A does not have any adverse effect on cell viability in vitro, at the dose range used.Pre-Clinical in vitro experiments with Composition APeptides within Composition A survive in vitro Simulated Gastrointestinal Digestion and Traverse the Epithelial LayerGastrointestinal Digestion Analysis and Transwell Absorption AssaysThe stability of Composition A was assessed through the upper gut tract in vitro, this consisted of 2-hrs of the gastric phase followed by 2-hrs of the intestinal phase. It was shown that peptides of SEQUENCE ID NO. 1 , 2, 4 and 5 survived the proteolytic effect of pepsin, the acidic conditions of the stomach and, subsequently, 2-hrs simulated intestinal digestion (Table x). The intact peptide pep_3KDR0P was not discovered post-gastric phase suggesting it may have been cleaved to a shorter sequence. Depending on where this cleavage occurred, it may retain bioactive capabilities.The bioavailability of the peptides was tested by treating a Caco-2:HT29 intestinal barrier with S-GID Composition A using an FDA approved technique to measure human intestinal permeability (Li et al (2016) Planta Med. 82, 1202-7; Larregieu (2013) AAPS J. 15, 483-97). The integrity of the intestinal barrier was maintained across the study as the TEER values were not significantly altered pre- and post-treatment and did not differ from negative control (cells with medium, data not represented). Interestingly, three peptides (SEQ ID NO. 1 , SEQ ID NO. 2 and SEQ ID NO. 4) were able to cross the intestinal co-culture and, therefore, likely to reach target organs downstream (Table 19). This also underlies that these peptides are not only resistant to stomach and intestinal proteases but also to the metabolic activity of brush border enzymes such aminopeptidases, endopeptidases and carboxypeptidases.Table 19: Summary of peptides within Composition A that survive S-GID and transwell absorption assays.Anti-Inflammatory StudiesCytokine arrayThe Proteome Profiler Human XL Cytokine Array kit was used to measure the secretion of various cytokines from THP1 cells when either untreated or pre-treated with Composition A 500 pg / ml for 24 hours prior to stimulation with LPS 100 ng / ml, for a further 24 hours. This array provides a high throughput screening approach to investigate potential cytokines andtargets which the composition of the invention can modulate. Figure 7 provides a visual representation of the stimulation effect that LPS has, activating the pro-inflammatory pathways in the THP1 cells compared to the untreated cells. Furthermore, it highlights the modulatory effect of Composition A on a subset of proteins where the expression of the cytokines is similar to that of the untreated cells. Of the 105 human proteins contained in the kit, Composition A was shown to modulate the expression of 13 proteins in particular. Among them are important mediators of inflammatory responses including Macrophage migration inhibitory factor (MIF) which is critically involved in immune function during anxiety, depression and stress and is a known factor in inflammation associated with sleep apnoea; VEGF which has a role in hippocampal neurogenesis and response to stress; Osteopontin, which triggers different leucocytes and induce pro-inflammatory cytokine secretion; RANTES which promotes recruitment and activation of inflammatory monocytes, lymphocytes and mast cells; and B cell activation factor (BAFF), a proinflammatory cytokine involved in the regulation of both innate and adaptive immune responses.DISCUSSIONHigh levels of stress in everyday life are driving poor quality sleep for millions of people worldwide. The knock-on effects this can have on physical, mental, and societal health is alarming. Prescribed sleep medicines fall short of solving the growing problem as unconsciousness alone does not lead to cellular restoration, tissue repair, memory consolidation or many of the other important biological processes which happen during the phases of a natural healthy sleep. Natural sleep remedies have been used for centuries; however, their safety and efficacy are disputed, and their mechanisms of action and molecular targets are usually unknown.The current inventors have identified bioactive peptides within the proteome of Oryza sativa to induce serenity and promote healthy sleep.The peptides were characterised using MS and tested to confirm bioactivity. Peptides of the invention have been characterised for orexin antagonist activity and anti-inflammatory properties, as well potential anti-anxiolytic properties. Critically, these peptides exert no detectible effect on cell viability. Furthermore, the peptides were capable of surviving simulated gastrointestinal digestion as well as being able to traverse across the intestinal epithelial later in vitro.The current invention significantly augments cortisol secretion from adrenal cortex cells as well as exert anti-inflammatory effects. These effects were confirmed in vitro.EquivalentsThe foregoing description details presently preferred embodiments of the present invention. Numerous modifications and variations in practice thereof are expected to occur to those skilled in the art upon consideration of these descriptions. Those modifications and variations are intended to be encompassed within the claims appended hereto.

Claims

Claims1 . A peptide up to 50 amino acids in length, comprising an amino acid sequence selected from SEQUENCE ID NO. 1 to SEQUENCE ID NO. 5 and 97 to 100 or an effective variant of the amino acid sequence.

2. The peptide of Claim 1 , wherein the variant comprises 1 to 3 amino acid changes compared with the sequence and wherein the or each amino acid change is independently selected from a deletion, addition, substitution and insertion.

3. The peptide of Claim 1 or 2, wherein the peptide is a sleep promoting peptide.

4. The peptide of any one of the preceding claims, wherein the peptide is an antiinflammatory peptide, and / or anti anxiolytic peptide.

5. The peptide of any one of the preceding claims, wherein the variant comprises an amino acid sequence selected from SEQUENCE NO. 6 to 96 and 101 to 139.

6. The peptide of any one of the preceding claims, wherein the peptide is modified, preferably to increase the stability of the peptide.

7. A conjugate comprising one or more peptides of any one of Claims 1 to 6, conjugated, linked or fused to a binding partner.

8. A composition comprising one or more peptides of any one of Claims 1 to 6 or the conjugate of Claim 7.

9. The composition of Claim 8, comprising a peptide comprising SEQUENCE ID NO. 1 or an effective variant thereof, a peptide comprising SEQUENCE ID NO. 2 or an effective variant thereof, a peptide comprising SEQUENCE ID NO. 3 or an effective variant thereof, a peptide comprising SEQUENCE ID NO. 4 or an effective variant thereof, and a peptide comprising SEQUENCE ID NO. 5 or an effective variant thereof.

10. The composition of Claim 8, comprising a peptide consisting of SEQUENCE ID NO. 1 , a peptide consisting of SEQUENCE ID NO. 2, a peptide consisting of SEQUENCE ID NO. 3, a peptide consisting of SEQUENCE ID NO. 4 and a peptide consisting of SEQUENCE ID NO. 5.

11. The composition of Claim 8, comprising a peptide comprising SEQUENCE ID NO. 1 or an effective variant thereof, a peptide comprising SEQUENCE ID NO. 3 or an effective variant thereof, and / or a peptide comprising SEQUENCE ID NO. 100 or an effective variant thereof12. The composition of Claim 11 , comprising a peptide consisting of SEQUENCE ID NO. 1 , a peptide consisting of SEQUENCE ID NO. 3 and a peptide consisting of SEQUENCE ID NO. 100.

13. The composition of any one of Claims 8 to 12, which is a powder.

14. A nutritional or dietary supplement comprising a peptide of any one of Claims 1 to 6, a conjugate of Claim 7, or a composition of any one of Claims 8 to 12.

15. A peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 114, for use in promoting sleep in a subject.

16. A non-therapeutic method of promoting sleep in a subject, the method comprising administration of a peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, to the subject.

17. A peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, invention for use in reducing cortisol in a subject.

18. A peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, invention for use treating or preventing stress or anxiety in a subject.

19. A non-therapeutic method of reducing fatigue in a subject, the method comprising administration of a peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, to the subject.

20. A peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, for use in prevention or treatment of an inflammatory disorder in a subject.

21. A non-therapeutic method of reducing inflammation in a subject, comprising administration of a peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, to the subject.

22. A non-therapeutic method of increasing focus in a subject, the method comprising administration of a peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, to the subject.

23. A non-therapeutic method of improving cognitive function or ability in a subject, the method comprising administration of a peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, to the subject.

24. A peptide of any one of Claims 1 to 6, a conjugate of Claim 7, a composition of any one of Claims 8 to 13 or a supplement of Claim 14, for use in preventing cognitive decline or improving cognitive function in a subject, wherein the subject is one with a disorder or disease that negatively impacts cognition in a subject.

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