MÉTODOS PARA MELHORAR A QUALIDADE DO SONO E / OU RESULTADOS COMPORTAMENTAIS SUBSEQUENTES USANDO UM FLAVONOIDE OU ÁCIDO FENÓLICO

Abstract

The present invention generally relates to the use of a composition to improve sleep quality and / or subsequent behavioural outcomes, in particular whole day sustained cognitive performance. More particularly, the present disclosure relates to administration of a composition comprising a flavonoid and / or phenolic acid compound, at a predetermined time before consumption of a meal, concurrently with consumption of a meal or at a predetermined time before sleep.

Description

1 / 22 Methods for Improving Sleep Quality and / or Subsequent Behavioral Outcomes Using a Flavonoid or Phenolic Acid

[001] The present invention generally relates to the use of a composition to improve sleep quality and / or subsequent behavioral outcomes, in particular sustained cognitive performance throughout the day. More particularly, the present invention relates to the administration of a composition comprising a flavonoid compound and / or phenolic acid, at a predetermined time before consuming a meal, simultaneously with consuming a meal, or at a predetermined time before bedtime. BACKGROUND

[002] Sleep is a crucial biological function and is considered an important regulator of health and well-being throughout life. Good sleep quality is associated with benefits for brain function, mood and mental performance, cardiovascular health and immunity (Alvarez et al., 2004), while poor sleep quality can lead to negative consequences for health and well-being (Hublin et al., 2007).

[003] The typical sleep architecture is composed of two components: non-rapid eye movement (NREM; slow-wave sleep - SWS) and rapid eye movement (REM) sleep. In general, sleep quality is considered to be driven by the total duration of SWS, while both SWS and REM have been considered, together, as contributing to benefits the following day, such as improved cognition. SWS and REM sleep are associated with distinct physiological states, including different requirements in nocturnal energy metabolism, substrate oxidation, and blood glucose management. Petition 870250082314, dated 12 / 09 / 2025, page 10 / 52 2 / 22

[004] Sleep quality is strongly associated with cognitive functioning, mood, and feelings of vitality and energy the following day. From a scientific perspective, sleep has been consistently associated with cognitive and mood benefits in humans (for reviews, see Palmer & Alfano, 2017; Rasch & Born, 2013; Walker, 2009). Among the different sleep stages, it has been suggested that the duration of SWS sleep is more closely linked to declarative memory, while REM sleep underlies the ability to synthesize abstract information, such as pattern recognition in newly acquired information (non-declarative; Rasch & Born, 2013; Walker, 2009). More recent observations on the function of each sleep stage suggest that SWS and REM may have complementary functions in consolidating newly acquired information (for different theories, see Rasch & Born, 2013).

[005] Furthermore, sleep needs change throughout life and sleep quality declines as we age (Madrid-Valero JJ et al. (2017). Gac sanit,31, 18-22.). Poor sleep in adulthood has been associated with ramifications in subjective health, quality of life (Magee CA et al.(2011). Sleep med.,12(4), 346-350) and progression of cognitive decline and dementia (Hudon C et al (2020). Neuropsychol Rev,30, 558-579).

[006] Most of the evidence on the role of sleep in next-day performance comes from sleep deprivation studies, with evidence suggesting that both sleep disruption and sleep deprivation can negatively affect aspects of cognition, including declarative memory, memory encoding and recall, and cognitive flexibility in using existing information to combine it in new ways (Walker, 2009). Among the cognitive domains strongly influenced by sleep, daytime alertness and subjective alertness levels are highly correlated with sleep duration. Petition 870250082314, dated 12 / 09 / 2025, page 11 / 52 3 / 22 sleep (Jewett et al., 1999). In fact, vigilance tasks have been consistently used as highly sensitive measures of sleep loss (Basner & Dinges, 2011). Furthermore, sleep-related difficulties can have significant negative effects on emotion regulation through a variety of mechanisms, including reduced capacity to downregulate amygdala activation to negative information. Specifically, studies have found that sleep deprivation can cause an almost 60% increase in amygdala activity when participants view negative images (review, Palmer & Alfano, 2017).

[007] Overall, although knowledge about the direct effect of nutrients on the brain and their mode of action to promote sleep is developing, there is still some need to identify dietary interventions to improve next-day benefits and the mechanisms by which this can affect subjective and objective cognitive performance and mood. SUMMARY

[008] Consequently, an objective of the present invention is to provide a method for improving sleep quality and / or subsequent behavioral outcomes. It also provides a method for treating, preventing, and / or reducing at least one risk, incidence, or severity of at least one condition for which improved sleep quality is beneficial. The method comprises orally administering to an individual in need a composition comprising an effective amount of at least one compound selected from the group consisting of a flavonoid, a phenolic acid, or a combination thereof.

[009] In some modalities, the subsequent behavioral outcome includes one or more of the following: (a) less frequent and / or less severe sleepiness, stress, tension / anxiety, fatigue Petition 870250082314, dated 12 / 09 / 2025, page 12 / 52 4 / 22 ga / inertia or depression / lack of motivation, anger / hostility, subjective frustration and / or (b) greater and / or better sleep onset, relaxation, calmness, alertness, vigor / activity, sympathy, cognition, memory, working memory, attention, vigilance, processing speed, fat use, weight control, immunity, subjective perceptions of mental, physical and temporal demands, subjective perception of performance or mood the following day.

[0010] In another modality, the subsequent behavioral outcome is sustained cognitive performance throughout the day.

[0011] In some forms, the flavonoid is rutin, quercetin, isoquercetin, luteolin, or a combination thereof.

[0012] In some embodiments, phenolic acid is caffeic acid, vanillic acid, chlorogenic acid, syringic acid, or a combination thereof.

[0013] In some forms, the composition is administered to the individual at a predetermined time before consuming a meal and / or simultaneously with consuming a meal.

[0014] In another modality, the compound is administered to the individual at night, preferably at a predetermined time before going to sleep.

[0015] Additional features and advantages are described in this document and will become apparent from the detailed description below and the figures. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 (A, B, C, D) shows the effect of active treatment compared with placebo on actigraphy measures of sleep onset latency (A), self-reported sleep onset latency (B), and self-reported next-day effects on sleepiness / alertness (C). Values ​​represent the smallest squared mean (±SE). The p-value represents a significant difference between the control group and the active treatment group. Petition 870250082314, dated 12 / 09 / 2025, page 13 / 52 5 / 22 of treatment.

[0017] Figure 2 (A, B) shows the effect of the active treatment compared to placebo on mood assessments. A. Mood States Profile - Vigor / Activity domain; B. Brief Mood Introspection Scale (BMIS) - Negative Relaxed Dimension, respectively. Values ​​represent the smallest squared mean (±SE). The p-value represents a significant difference between the control group and the treatment group. DETAILED DESCRIPTION Definitions

[0018] Some definitions are provided below. However, the definitions may be located in the Modalities section below, and the Definitions heading above does not mean that such disclosures in the Modalities section are not definitions.

[0019] All percentages refer to the total weight of the composition unless expressly stated otherwise. Similarly, all ratios are by weight unless expressly stated otherwise. As used herein, the terms approximately, roughly and substantially are understood as referring to numbers in a range of numerals, for example, the range of -10% to +10% of the reference number, preferably -5% to +5% of the reference number, more preferably -1% to +1% of the reference number, most preferably -0.1% to +0.1% of the reference number.

[0020] Furthermore, all numerical ranges in the present invention should be understood as including all whole numbers, fractional or non-fractional, within the range. In addition, these numerical ranges should be interpreted as providing support for a claim directed to any number or subset of numbers that is within that range. For example, a description from 1 to Petition 870250082314, dated 12 / 09 / 2025, page 14 / 52 6 / 22 should be interpreted as supporting a range of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, and so on. The ranges defined using "between" include the aforementioned endpoints.

[0021] As used herein and in the appended claims, the singular form of a word includes the plural unless the context clearly indicates otherwise. Thus, references to a, an, or are generally inclusive of the plurals of the respective terms. For example, a reference to an ingredient or a method includes a plurality of such ingredients or methods. The term and / or used in the context of X and / or Y should be interpreted as X or Y or X and Y. Similarly, at least one of X or Y should be interpreted as X or Y or both X and Y.

[0022] Similarly, the words comprise, includes, and that which includes shall be interpreted inclusively rather than exclusively. Likewise, the terms includes, including, and or shall all be interpreted inclusively unless such interpretation is clearly excluded by the context. However, the embodiments provided by the present invention may not have any element that is not specifically disclosed in the present invention. Thus, a description of an embodiment defined using the term comprising / that which includes is also a description of embodiments that essentially consist of and consist of the disclosed components.The term essentially consisting of means that the modality or a component thereof comprises more than 50%, by weight, of the individually identified components, preferably at least 75%, by weight, of the individually identified components, more preferably at least 85%, by weight, of the individually identified components, with the highest preference at least 95%, by weight, of the individually identified components, for example at least. Petition 870250082314, dated 12 / 09 / 2025, page 15 / 52 7 / 22 99%, by weight, of the individually identified components.

[0023] When used herein, the term example, particularly when followed by a list of terms, is merely exemplary and illustrative and should not be considered exclusive or comprehensive. Any embodiment disclosed in the present invention may be combined with any other embodiment disclosed herein, unless expressly stated otherwise.

[0024] The term animal includes, but is not limited to, mammals, which includes, but is not limited to, rodents, aquatic mammals, domestic animals such as dogs and cats, farm animals such as sheep, pigs, cows and horses, and human beings. When the terms animal, mammal or a plural form thereof are used, these terms also apply to any animal that may experience the effect presented or intended to be presented by the context of the passage, for example an animal that benefits from the reduction of postprandial glucose. Although the term individual is frequently used in the present invention to refer to a human being, the present invention is not so limited. Consequently, the term individual refers to any animal, mammal or human being that may benefit from the methods and compositions disclosed in the present invention.

[0025] The terms relating to improving, promoting, enhancing and the like refer to the effects of the method disclosed herein on sleep quality, particularly the administration of a composition comprising a blackberry extract, at a predetermined time before the consumption of an evening meal and / or simultaneously with the consumption of an evening meal, in relation to the consumption of a meal formulated identically but without the blackberry extract provided by the composition. In some embodiments, sleep quality may be quantified by one or both of (a) a duration Petition 870250082314, dated 12 / 09 / 2025, p. 16 / 52 8 / 22 total slow-wave sleep (SWS) and / or (b) a total duration of rapid eye movement (REM) sleep. For example, improved sleep quality may be established by one or both of a longer total duration of SWS and / or a longer total duration of REM sleep. In some modalities, improved sleep quality is the improvement in one or more of i) sleep efficiency (e.g., measured by actigraphy data); ii) change in sleep latency (e.g., actigraphy data); iii) change in arousal after sleep onset (e.g., by actigraphy); iv) change in total sleep duration (minutes, actigraphy); v) time in bed; vi) minutes spent in bed after waking. In other modalities, sleep quality may be assessed through self-reports (e.g., Karolinska Sleepiness Scale (KSS) or Epworth Sleepiness Scale (ESS)).

[0026] For use in the present invention, the terms treat or treatment mean administering a composition as disclosed in the present invention to an individual who has a health problem to lessen, reduce or improve at least one symptom associated with the health problem, and / or lessen, reduce or block the progression of the health problem. The terms treatment and treat include prophylactic or preventive treatment (which prevents and / or slows the development of a pathological condition or a target disorder) and curative, therapeutic or disease-modifying treatment, including therapeutic measures that cure, slow, delay the symptoms and / or interrupt the progression of a diagnosed pathological condition or disorder; and treatment of patients at risk of contracting a disease or suspected of having contracted a disease, as well as patients who are ill or have been diagnosed with a disease or clinical condition.The terms "treatment" and "to treat" do not necessarily imply that an individual is treated until full recovery. The terms... Petition 870250082314, dated 12 / 09 / 2025, p. 17 / 52 9 / 22 Treatment and treating also refer to the maintenance and / or promotion of health in an individual who does not suffer from a disease but may be susceptible to developing an unhealthy condition. The terms treatment and treating are also intended to include the enhancement or otherwise optimization of one or more primary prophylactic or therapeutic measures. As non-limiting examples, treatment may be performed by a patient, a caregiver, a physician, a nurse, or another healthcare professional. The terms prevent and prevention mean administering a composition, as disclosed herein, to an individual who does not exhibit any symptoms of the condition to reduce or prevent the development of at least one symptom associated with the condition. Furthermore, prevention includes reducing the risk, incidence, and / or severity of a condition or disorder.

[0027] As used in this document, an effective amount is an amount that treats or prevents a deficiency, treats or prevents a disease or medical condition in an individual, or more generally reduces symptoms, manages disease progression, or provides a nutritional, physiological, or medical benefit to the individual. As used in this document, administration includes another person who provides a quoted composition to an individual so that the individual can consume the composition, and also includes merely the action of the individual consuming a quoted composition.

[0028] The terms food, food product and food composition mean a composition that is intended for ingestion by an individual, for example a human being, and that provides at least one nutrient to the individual. The term food and its related terms include any food, feed, snack, dietary supplement, treat or meal replacement intended for a human being or animal. A dietary supplement may be a supplement Petition 870250082314, dated 12 / 09 / 2025, p. 18 / 52 10 / 22 Oral feeding (OF) may be in the form of a solid powder, a powder stick, a capsule, or a solution. Animal feed includes foods or rations intended for any domesticated or wild species. In preferred embodiments, an animal feed represents a pelleted, extruded, or dry food, for example, extruded pet foods such as dog and cat food.

[0029] In the context of the present invention, the term beverage, beverage product and beverage composition means a liquid product or composition that is potable for ingestion by an individual such as a human being and provides water and may also include one or more nutrients and other ingredients that are safe for human consumption by the individual. Modalities

[0030] One aspect of the present invention is a method for improving sleep quality and / or subsequent behavioral outcomes. In another aspect, the present invention provides a method for treating, preventing and / or reducing at least one of the risks, incidence or severity of at least one condition for which improved sleep quality is beneficial. The method comprises orally administering a composition comprising an effective amount of at least one compound selected from the group consisting of a flavonoid, phenolic acid or a combination thereof.

[0031] In one embodiment, the composition is administered to the individual at a predetermined time before or simultaneously with the consumption of a meal. Alternatively, the composition is administered to the individual at night, preferably at a predetermined time before bedtime.

[0032] Preferably, the meal should be an evening meal, for example, a balanced evening meal. Petition 870250082314, dated 12 / 09 / 2025, p. 19 / 52 11 / 22

[0033] If the composition is administered outside of a meal, it can be delivered in the form of a capsule, liquid, etc.

[0034] Subsequent behavioral outcomes enhanced by improved sleep quality include one or more of (a) less frequent and / or less severe subjective frustration, stress, tension / anxiety, fatigue / inertia or depression / sadness, anger / hostility, and / or (b) faster and / or better sleep onset, relaxation, calmness, alertness, vigor / activity, friendliness, cognition, memory, working memory, attention, vigilance, processing speed, fat use, weight management, immunity, subjective perceptions of mental and physical conditions, temporal demands, subjective perception of performance or mood the following day.

[0035] In a preferred modality, the subsequent behavioral outcome is sustained cognitive performance throughout the day.

[0036] The individual may be a mammal, such as a human, canine, feline, equine, caprine, bovine, ovine, porcine, cervine, or a primate. Preferably the individual is a human.

[0037] In some forms, the composition is administered to a human adult with sleep problems.

[0038] In some embodiments, the flavonoid is one of rutin, quercetin, isoquercetin, luteolin, or a combination thereof. The flavonoid may be from any suitable source and may be isolated and / or chemically synthesized. In a preferred embodiment, rutin, quercetin, isoquercetin, and / or luteolin are obtained from plant sources.

[0039] Rutin may be obtained from onions, buckwheat, lemon blossoms, elderflowers, hawthorn, rue, St. John's wort, ginkgo, apples, and other fruits and vegetables. Quercetin is the aglycone form of several other flavonoid glycosides, such as rutin and quercitrin, found in citrus fruits, buckwheat and onions, green tea, apples, berries, ginkgo biloba, St. John's wort, elderberry, and other fruits and vegetables. Petition 870250082314, dated 12 / 09 / 2025, p. 20 / 52 12 / 22 American guar and others. Isoquercitrin is the 3-O-glycoside of quercetin. Isoquercitrin can be isolated from several plant species, including Mangifera indica (mango) and Rheum nobile (noble rhubarb). It is also present in the leaves of Annona squamosa and Camellia sinensis (tea). Luteolin can be found in fruits and vegetables such as celery, chrysanthemum flowers, bell peppers, carrots, onion leaves, broccoli, and parsley.

[0040] In one embodiment, the flavonoid is from mulberry extract. It may be of any Morus origin, including, but not limited to, white mulberry (Morus alba L.), black mulberry (Morus nigra L.), American mulberry (Morus celtidifolia Kunth), red mulberry (Morus rubra L.), hybrid forms between Morus alba and Morus rubra, Korean mulberry (Morus australis), Himalayan mulberry (Morus laevigata), and combinations thereof.

[0041] The mulberry extract applicable to the present invention may be derived from different parts of the mulberry tree, including bark (trunk, twigs or roots), roots, buds, twigs, new shoots, leaves, fruit and combinations thereof. The mulberry extract may be in the form of, for example, dry powders, such as ground dry powders from different parts of the tree. The initial mulberry plant material may be fresh, frozen or dried mulberry materials. The extract may be used as a liquid or dry concentrated solid. Typically, this extract includes at least about 1% w / v of 1-DNJ. In a preferred embodiment, the mulberry extract is a mulberry leaf extract.

[0042] Plant extracts and plants according to the present invention can be prepared by procedures well known in the art.

[0043] The compositions of the present invention may typically comprise from about 1% to about 50%, including about 2% Petition 870250082314, dated 12 / 09 / 2025, p. 21 / 52 13 / 22 to about 30%, as well as from about 5% to about 20%, and also including from about 10% to about 15% of that extract by weight of the composition.

[0044] The composition may comprise an amount of flavonoid effective in promoting better sleep quality for the individual. It may vary from 0.01 mg to about 1 g, preferably from 0.1 mg to 1 g, even more preferably from 1 mg to about 1 g of each component per serving of the composition.

[0045] In some embodiments, phenolic acid is caffeic acid, vanillic acid, chlorogenic acid, syringic acid, or a combination thereof.

[0046] Caffeic acid can be found in the bark of Eucalyptus globulus, in the barley grain Hordeum vulgare and in the herb Dipsacus asperoides, in the freshwater fern Salvinia molesta and in mushrooms. Vanillic acid is found in some forms of vanilla and many other plant extracts, such as the root of Angelica sinensis. Chlorogenic acid (CGA) is produced by certain plant species and is an important component of coffee. Syringic acid is a naturally occurring phenolic compound and dimethoxybenzene that is commonly found as a plant metabolite. Syringic acid can be found in various plants, including Ardisia elliptica and Schumannianthus dichotomus.

[0047] Preferably, the total amount of phenolic acid in the composition is effective in promoting better sleep quality for the individual.

[0048] In one embodiment, the composition further comprises an ingredient that reduces the glycemic response in the individual. In some embodiments, the ingredient that reduces the glycemic response is one or more of the following: tryptophan (for example, as a free amino acid and / or in a protein such as whey protein), a glucocorticoid inhibitor Petition 870250082314, dated 12 / 09 / 2025, page 22 / 52 14 / 22 cosidase as 1-deoxynojirimycin (DNJ) (e.g., isolated or in a mulberry leaf or fruit extract) or phloridzin (e.g., isolated or in an apple extract), arginine-proline dipeptide (AP) (e.g., isolated or in a milk protein hydrolysate), a fiber, a resistant starch, a beta-glucan, A-cyclodextrin, glucosidase (e.g., isolated and / or as part of a composition such as mulberry leaf extract) or an amylase inhibitor (e.g., isolated and / or in a composition such as white bean or wheat albumin).

[0049] In some forms, the composition is administered once a day (for example, with the evening meal, preferably not with other meals and / or not at other times of the day) for a total duration of at least 3 days, preferably for at least one week, more preferably for at least two weeks.

[0050] In some forms, the composition is administered at a predetermined time before bedtime. It can be administered immediately before bedtime up to 3 hours before, preferably up to 2 hours before, 1 hour before, 30 minutes before bedtime.

[0051] In some embodiments, the composition is a cereal snack, a beverage (e.g., a ready-to-drink beverage) containing cereal, a soup, a porridge, a broth, or a pudding and is administered to a human adult. In some embodiments, the composition is administered to a human child aged 1 to 3 years.

[0052] The composition according to the invention can be added to or mixed into the meal, or it can be consumed as an accompaniment to the meal. In a preferred embodiment, the composition comprising EA according to the invention is in the form of a powder or granules to be added to or mixed into the meal, preferably sprinkled over the meal.

[0053] As used herein, meal refers to one or more products Petition 870250082314, dated 12 / 09 / 2025, p. 23 / 52 15 / 22 food items consumed substantially at the same time; preferably, in such a way that one or more proteins, one or more carbohydrates, one or more fats, and at least one micronutrient are supplied with the consumption of the meal; more preferably, in such a way that one or more proteins, one or more carbohydrates, one or more fats, one or more vitamins, and one or more minerals are supplied with the consumption of the meal. Preferably, the meal comprises a plurality of food items. As used herein, a balanced meal refers to a meal that supplies all of the protein, carbohydrate, fat, vitamins, and minerals in amounts and proportions adequate to maintain the health or growth of an individual.The amounts and proportions of protein, carbohydrate, fat, vitamins, and minerals necessary to maintain health or growth can be determined in accordance with current food and nutrition regulations, and any specific individual needs, for example, based on age, physical activity, and / or gender.

[0054] For example, current energy, macronutrient, and fluid recommendations from the Food and Nutrition Board of the Institutes of Medicine (IOM) recommend an acceptable macronutrient distribution range for carbohydrates (45% to 65% of energy), protein (10% to 35% of energy), and fat (20% to 35% of energy) for active individuals. In one modality, the balanced meal provides 45 to 65% of total calories from carbohydrates, 20 to 35% of total calories from fat, and 10 to 35% of total calories from protein. In one modality, the meal provides 200 kcal to 1,000 kcal to the individual, preferably 250 kcal to 900 kcal, most preferably 300 kcal to 850 kcal, and most preferably 350 kcal to 800 kcal.

[0055] In some modalities, evening meal means a Petition 870250082314, dated 12 / 09 / 2025, p. 24 / 52 16 / 22 meal consumed approximately 1.0 hour to approximately 6.0 hours before sleep onset, preferably a meal approximately 2.0 hours to approximately 5.0 hours before sleep onset, more preferably a meal approximately 2.5 hours to approximately 4.5 hours before sleep onset, with maximum preference approximately 3.0 hours to approximately 4.0 hours before sleep onset.

[0056] In some modalities, evening meal means a meal consumed from around 4:30 pm to around 11:30 pm in the geographical region where the individual is located, preferably a meal consumed from around 5 pm to around 11 pm in the geographical region where the individual is located, with greater preference, a meal consumed from around 5:30 pm to around 10:30 pm in the geographical region where the individual is located, with maximum preference, a meal consumed from around 6 pm to around 10 pm in the geographical region where the individual is located.

[0057] Preferably, the food or supplement according to the present invention is administered orally to the individual in a form selected from the group consisting of a dairy beverage and a non-dairy beverage, and the unit dosage form is a predetermined quantity of the beverage.

[0058] In some embodiments, the composition may be a ready-to-drink (PPC) beverage in a container, and the unit dosage form is a predetermined quantity of the PPC beverage sealed in the container, which is opened for oral administration.

[0059] In other embodiments, the method comprises forming the composition by reconstituting a unit dosage form of a powder in water or milk to form the composition subsequently administered orally to the individual (for example, within about ten minutes after reconstitution, within about five minutes after reconstitution, or within about one minute after reconstitution). Petition 870250082314, dated 12 / 09 / 2025, p. 25 / 52 17 / 22 (constitution). The unit dosage form of the powder may be sealed in a sachet or other packaging, which may be opened for reconstitution and subsequent oral administration.

[0060] In some embodiments, the unit dosage form of the composition may further comprise one or more of melatonin, for example, as pistachio powder (e.g., about 0.1 to about 0.3 mg of melatonin), vitamins B3 and B6 (e.g., from about 15% of NRV to about 2 mg), magnesium (e.g., about 40 mg of magnesium) and / or zinc (e.g., from about 15% of NRV to about 15 mg). In some embodiments, the composition may further comprise one or more of gamma-aminobutyric acid (GABA), alpha-casozepine or theanine.

[0061] The unit dosage form of the composition may additionally contain excipients, emulsifiers, stabilizers and mixtures thereof. The composition may include any nutritional or non-nutritional ingredient that adds bulk, and in most cases will be substantially inert and will not significantly negate the blood glucose benefits of the composition. The bulking material typically includes a fiber and / or carbohydrate with a low glycemic index.

[0062] Suitable carbohydrate sources for inclusion in the compositions disclosed herein include those with a low glycemic index such as fructose and low ED maltodextrins, as such ingredients do not introduce a high glycemic load into the composition. Other suitable components of the composition include any dietary fiber suitable for human or animal use, including soluble and insoluble fiber, especially soluble fiber. Beneficial effects of soluble fiber on the glycemic response have been widely reported. Non-limiting examples of suitable soluble fiber include FOS, GOS, inulin, resistant maltodextrins, partially soluble guar gum Petition 870250082314, dated 12 / 09 / 2025, page 26 / 52 18 / 22 hydrolyzed protein, polydextrose and combinations thereof.

[0063] A non-limiting example of commercially available fiber for composition includes Sunfiber® (Taiyo International, Inc.), which is a water-soluble dietary fiber produced by enzymatic hydrolysis of guar gum granules; Fibersol 2™ (Archer Daniels Midland Company), which is a digestion-resistant maltodextrin; and polydextrose.

[0064] In one embodiment, the composition may also include tryptophan. In a preferred embodiment, the composition comprises protein comprising at least a portion of tryptophan in the composition, preferably whey protein as whey protein isolate; a mixture of whey protein and casein; or soy protein. In some embodiments, the supplement is administered in a unit dosage form comprising about 120 mg to about 5 g of tryptophan.

[0065] In one embodiment, the composition may comprise tryptophan, an extract as a source of flavonoid and / or phenolic acid, and a soluble fiber. In a preferred embodiment, the composition comprises a soluble fiber selected from polydextrose, a resistant maltodextrin (such as Fibersol-2 soluble corn fiber), and combinations thereof.

[0066] The composition may also include other fillers, stabilizers, cake anti-formation agents, antioxidants or combinations thereof.

[0067] The composition may additionally comprise one or more additional components, such as minerals; vitamins; salts; or functional additives including, for example, palatability enhancers, colorants, emulsifiers, antimicrobial agents or other preservatives. Non-limiting examples of minerals suitable for the compositions disclosed herein include calcium, phosphorus, potassium, sodium, iron, chloride Petition 870250082314, dated 12 / 09 / 2025, page 27 / 52 19 / 22 iron, boron, copper, zinc, magnesium, manganese, iodine, selenium, chromium, molybdenum, fluoride and any combination thereof. Non-limiting examples of vitamins suitable for the compositions disclosed herein include water-soluble vitamins (such as thiamine (vitamin B1)), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (vitamin B7), myo-inositol (vitamin B8), folic acid (vitamin B9), cobalamin (vitamin B12 and vitamin C) and fat-soluble vitamins (such as vitamin A, vitamin D, vitamin E and vitamin K), including salts, esters or derivatives thereof.

[0068] All references in the present invention to treatment include curative, palliative, and prophylactic treatment. Treatment may also include halting the progression of the severity of a disease. Both human and veterinary treatments are within the scope of the present invention. Preferably, the composition is administered in a unit dosage form or portion comprising a therapeutically effective or prophylactically effective amount of the ingredient that reduces the glycemic response. Non-limiting examples: Example 1

[0069] The following non-limiting example presents experimental data that develop and support the concepts of the embodiments provided by the present invention.

[0070] The aim of the present study was to evaluate the efficacy of an active formulation of mulberry leaf extract, tryptophan, and vitamins and minerals (MlT) containing 0.75 g of Mulberry Leaf Extract (with 1% 1-deoxyjirinomycin) and 120 mg of tryptophan to promote better sleep and mood the following day and cognitive performance in healthy adults with poor sleep. Methods Petition 870250082314, dated 12 / 09 / 2025, page 28 / 52 20 / 22

[0071] The clinical trial design was a double-blind, controlled, randomized, 2-arm, sequential crossover trial (ClinicalTrials.gov Identifier: NCT05372900). Adults (aged 25–50 years) with poor sleep (Pittsburgh Sleep Quality Index SQI>5 and <85% sleep efficiency over 14 days of screening) received standardized meals and concomitant intake of the active formulation MlT or placebo consumed approximately 4 hours before bedtime. The intervention phases lasted 14 days, with a treatment withdrawal period of 28–42 days. The primary outcomes were Sleep Efficiency (SE) and Sleep Onset Latency (SOL) measured by actigraphy. Secondary outcomes included self-reported mood, sleep quality (measured 1 hour after waking), and objective measures of average daily cognitive performance. Results

[0072] Linear mixed model analysis was conducted with intention-to-treat, adjusting baseline and treatment order for sleep, mood, and cognitive outcomes. There was no significant treatment effect on SE (p=0.23). However, there was a significant improvement in SOL actigraphy (p=0.026) and self-reported SOL (p=0.048) (see Figures 1A and 1B) after comparing active treatment to control. Subjective self-report measures (Karolinska Sleepiness Scale) also showed that participants felt less sleepy (p=0.042) (see Figure 1C) the following morning.

[0073] The Vigor-activity subscale (1 hour post-wake) assessed using the Mood States Profile questionnaire was significantly increased under the active treatment condition (6.63 ± 0.43) compared to the control (5.82 ± 0.40) (p=0.038) (Figure 2A). In the post-wake state, there was also a significant difference with the treatment condition (11.65 ± 0.31) in the Negative / Relaxed dimension of the Petition 870250082314, dated 12 / 09 / 2025, page 29 / 52 21 / 22 Brief Mood Introspection Scale compared to the control condition (12.05 ± 0.31) (p=0.003).

[0074] Active treatment resulted in participants objectively falling asleep faster, feeling less sleepy and more relaxed, and more energetic (vigor) the following morning. Furthermore, the results demonstrate that sleep onset, quality, and mood outcomes can be improved through supplemental nutritional intervention and may represent a simple and convenient strategy to support improved sleep and its related health outcomes in adult populations. Several observational studies have shown a link between sleep duration and cognitive performance, including working memory and arithmetic tasks [1, 2]. Additionally, other studies have demonstrated a connection between sleep quality and cognitive performance in tasks involving sustained attention, memory (emotional memory, working memory, recall memory, visuospatial memory), and verbal fluency [2-5].Além disso, a qualidade do sono também foi associada ao desempenho acadêmico [6, 7]. 1. Lo, J.C., et al., Self-reported sleep duration and cognitive performance in older adults: a systematic review and meta-analysis. Sleep Med, 2016. 17: págs. 87-98. 2. Sternberg, D.A., et al., The largest human cognitive performance dataset reveals insights into the effects of lifestyle factors and aging. Front Hum Neurosci, 2013. 7: pág. 292. 3. Steenari, M.R., et al., Working memory and sleep in 6- to 13-year-old schoolchildren. J Am Acad Child Adolesc Psychiatry, 2003. 42(1): págs. 85-92. 4. Yun, C.H., et al., Daytime sleepiness associated with poor sustained attention in middle and late adulthood. Sleep Med, 2015. 16(1): págs. 143-51. Petição 870250082314, de 12 / 09 / 2025, pág. 30 / 52 22 / 22 5. Gobin, C.M., et al., Poor sleep quality is associated with a negative cognitive bias and decreased sustained attention. J Sleep Res, 2015. 24(5): págs. 535-42. 6. Gilbert, S.P. e C.C. Weaver, Sleep Quality and Academic Performance in University Students: A Wake-Up Call for College Psychologists. Journal of College Student Psychotherapy, 2010. 24(4): págs. 295-306. 7. Seun-Fadipe, C. e K. Mosaku, Sleep quality and academic performance among Nigerian undergraduate students. Journal of Systems and Integrative Neuroscience, 2017. 3.

[0075] It should be understood that various changes and modifications to the present preferred embodiments described in the present invention will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present matter and without diminishing its intended advantages. It is therefore intended that such changes and modifications are covered by the appended claims. Petition 870250082314, dated 12 / 09 / 2025, page 31 / 52

Claims

1 / 5 CLAIMS 1. Use of an effective amount of at least one compound selected from the group consisting of a flavonoid, a phenolic acid or a combination thereof, characterized in that it is for the preparation of an oral composition to improve sleep quality and / or subsequent behavioral outcomes in an individual, and / or to treat, prevent and / or reduce at least one of the risk, incidence or severity of at least one condition for which improved sleep quality is beneficial in an individual.

2. Use according to claim 1, characterized in that the flavonoid is one of rutin, quercetin, isoquercetin, luteolin, or a combination thereof.

3. Use, according to claim 1 or 2, characterized in that the phenolic acid is one of caffeic acid, vanillic acid, chlorogenic acid, syringic acid or a combination thereof.

4. Use, according to any of claims 1 to 3, characterized in that the subsequent behavioral outcome includes one or more of the following: (a) less frequent and / or less severe drowsiness, stress, tension / anxiety, fatigue / inertia or depression / lack of motivation, anger / hostility, subjective frustration and / or (b) greater and / or better sleep onset, relaxation, calmness, alertness, vigor / activity, empathy, cognition, memory, working memory, attention, vigilance, processing speed, fat use, weight control, immunity, subjective perceptions of mental, physical and temporal demands, subjective perception of performance or mood the following day.

5. Use, according to any one of claims 1 to 4, characterized in that the subsequent behavioral result is sustained cognitive performance throughout the day.

6. Use, according to any of the claims in Petition 870250082314, dated 12 / 09 / 2025, page 39 / 52 2 / 5 4, characterized by the fact that the total amount of at least one flavonoid and / or phenolic acid compound in the composition is effective in promoting better sleep quality for an individual.

7. Use, according to any one of claims 1 to 5, characterized in that at least one flavonoid and / or phenolic acid is in the form of a plant or vegetable extract.

8. Use, according to any one of claims 1 to 7, characterized in that the composition further comprises one or more of the following: melatonin, vitamin B3, vitamin B6, magnesium, zinc, gamma-aminobutyric acid (GABA), alpha-casozepine or theanine.

9. Use, according to any one of claims 1 to 6, characterized in that the composition further comprises an ingredient that reduces the glycemic response, wherein the ingredient that reduces the glycemic response is one or more of the following: tryptophan, a glucosidase inhibitor, polymeric piperidine, 1-deoxynojirimycin (DNJ), arginine-proline dipeptide (AP), a fiber, a resistant starch, a beta-glucan, A-cyclodextrin, glucosidase or an amylase inhibitor.

10. Use according to claim 9, characterized in that the composition comprises protein having at least one tryptophan moiety, preferably whey protein, such as whey protein isolate; a mixture of whey protein and casein; or soy protein.

11. Use, according to any one of claims 1 to 9, characterized in that the composition is a liquid beverage, or a beverage ready for consumption, or a beverage formed by reconstituting a powder in a diluent.

12. Use, according to any one of claims 1 to 10, characterized in that the individual is a mammal, or a companion animal, or a human being. Petition 870250082314, dated 12 / 09 / 2025, p. 40 / 52 3 / 5 13. Use, according to any one of claims 1 to 11, characterized in that the composition is formulated and / or prepared to be given to the individual at a predetermined time before the consumption of a meal and / or simultaneously with the consumption of a meal.

14. Use, according to any one of claims 1 to 13, characterized in that the composition is formulated and / or prepared to be given to the individual at night, or at a predetermined time before sleep.

15. Oral composition to improve sleep quality and / or subsequent behavioral outcomes in an individual and / or to treat, prevent and / or reduce at least one of the risks, incidence or severity of at least one condition for which improved sleep quality is beneficial in an individual, characterized in that it comprises an effective amount of at least one compound selected from the group consisting of a flavonoid, a phenolic acid or a combination thereof.

16. An invention characterized by any of its embodiments or any applicable category of claim, for example, product or process or use, or any other type of claim encompassed by the matter initially described, disclosed or illustrated in the patent application, for example: A method for improving sleep quality and / or subsequent behavioral outcomes, comprising orally administering to an individual a composition comprising an effective amount of at least one compound selected from the group consisting of a flavonoid, a phenolic acid or a combination thereof;and / or Method for treating, preventing and / or reducing at least one risk, incidence or severity of at least one condition for which improved sleep quality is beneficial, comprising orally administering to an individual a composition comprising at least one compound selected from the group consisting of a flavonoid, a phenolic acid or a combination thereof; and / or Container containing an effective amount of at least one compound selected from the group consisting of a flavonoid, a phenolic acid or a combination thereof, or a composition, as defined in any of the preceding claims; and / or Use of a compound for the preparation of a composition for the treatment of diseases, disorders and / or conditions;and / or Composition, according to any of the preceding claims, further comprising one or more of the following: melatonin, vitamin B3, vitamin B6, magnesium, zinc, gamma-aminobutyric acid (GABA), alpha-casozepine or theanine; and / or Composition, according to any of the preceding claims, further comprising an ingredient that reduces the glycemic response, wherein the ingredient that reduces the glycemic response is one or more of the following: tryptophan, a glucosidase inhibitor, polymeric piperidine, 1-deoxynojirimycin (DNJ), arginine-proline dipeptide (AP), a fiber, a resistant starch, a beta-glucan, acyclodextrin, glucosidase or an amylase inhibitor;and / or liquid beverage and / or ready-to-drink beverage and / or beverage formed by reconstituting a powder in a diluent, comprising an effective amount of at least one compound selected from the group consisting of a flavonoid, a phenolic acid or a combination thereof, or a composition, as defined in any of the preceding claims. Petition 870250082314, dated 12 / 09 / 2025, p. 42 / 52 5 / 5

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