Melatonin for reducing hair molting in companion animals

Abstract

The present disclosure relates to the use of melatonin to reduce shedding in companion animals, such as canines or felines, including cats. The melatonin can be administered orally, such as in the form of a dietary supplement or a food composition. The present disclosure also relates to melatonin-containing food compositions, which can be selected from wet food compositions, semi-moist food compositions, and dry food compositions.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to European Patent Application No. 22194444.0, filed September 7, 2022, the entire contents of which are incorporated herein by reference. [Technical Field]

[0002] The present disclosure relates to maintaining the coat of companion animals. [Background technology]

[0003] The contribution of coat condition to environmental conservation and behavioral display in companion animals, including canines and felines, is well recognized. Important attributes of coat condition include appearance.

[0004] The hair growth cycle is generally believed to occur in cycles consisting of a growth phase (anagen), a regression phase (catagen), and a resting phase (telogen). After hair growth ceases, the lower part of the hair follicle regresses. During this catagen phase, the lower hair follicle ascends to the level of the arrector pili muscle, and the base of the fully formed hair shaft differentiates. Some time after the hair follicle enters the resting phase, the hair shaft falls out. Because this hair loss process is thought to have its own definition and regulation, some authors have called this cycle stage the "extrinsic" phase. Some authors have found that the largest exogenous component is bound to anagen, that the exogenous hair shaft base is different from the telogen hair shaft base, and that the shed hair shaft forms earliest (Non-Patent Document 1). However, to date, little is known about the mechanism and regulation of hair loss.

[0005] Shedding is a natural process that dogs, cats, and other animals go through. It consists of a complete replacement of the coat to adapt to the animal's needs, ensuring protection in the winter and protection from heat in the summer. Therefore, shedding usually occurs in the spring and autumn. Shedding is triggered by two main factors: changes in temperature and the number of hours of sunlight per day.

[0006] In animals, hair molting appears to depend on several parameters, including genetics, photoperiod, and hormones. Because hair molting appears to occur independently of the anagen phase of the hair follicle, the molting phase appears to have its own regulatory mechanism (Non-Patent Document 2).

[0007] However, the exact mechanisms that control the initiation of the different stages of the hair cycle remain to be elucidated.

[0008] Usually, the shedding process occurs naturally. However, this is not always the case; for example, long-haired cats are at risk of swallowing too much hair when cleaning themselves, which can lead to gastritis or intestinal blockages. To limit this risk, many cats regularly regurgitate undigested hairballs.

[0009] Currently, animal owners, including pet owners, deal with shedding by regularly brushing their animals' coats at least once a week to remove loose hair. Feeding animals with a proper balanced food regimen can also be helpful. Several nutritional supplement compositions containing vitamins, minerals, and essential amino acids are also commercially available, with the aim of maintaining a healthy and shiny coat. Raising animals in a stress-free environment is also known to contribute to the suppression of shedding. [Prior art documents] [Non-patent literature]

[0010] [Non-Patent Document 1] Milner et al., 2002, J Invest Dermatol, Vol. 119(3) : 640-644 [Non-patent document 2] Johnson, 1972, Mammalian Rev, Vol. 1 : 198-208; Milner et al., 2002, J Invest Dermatol, Vol. 119(3) : 640-644 Summary of the Invention [Problem to be solved by the invention]

[0011] There remains a need in the art to provide a technological solution for limiting shedding in companion animals, particularly canines and felines. [Means for solving the problem]

[0012] The present disclosure relates to the use of melatonin to reduce hair shedding in companion animals, preferably felines, most preferably cats.

[0013] The present disclosure also relates to a method for reducing hair shedding in a companion animal, comprising administering melatonin, preferably orally, to the companion animal, wherein the companion animal is preferably a feline, most preferably a cat.

[0014] In some embodiments, the melatonin is included in a melatonin-containing composition.

[0015] The melatonin-containing composition can be a dietary supplement or a complete food composition.

[0016] Melatonin or melatonin-containing compositions can be administered subcutaneously, transdermally, or intradermally.

[0017] In some embodiments, the melatonin is contained in an extract from a melatonin-producing microorganism, preferably an extract from a melatonin-producing yeast.

[0018] In some embodiments, the melatonin is administered daily.

[0019] In some embodiments, melatonin is administered orally in a daily dose ranging from about 0.5 mg / kg body weight to about 4 mg / kg body weight, such as, for example, a daily dose of about 2 mg / kg body weight.

[0020] The present disclosure further relates to a method for reducing hair shedding in a companion animal, comprising administering melatonin, preferably orally, to the companion animal, wherein the companion animal is preferably a feline, most preferably a cat.

[0021] The present disclosure also relates to a melatonin-containing complete food composition for companion animals selected from the group consisting of a wet complete food composition, a semi-moist complete food composition, and a dry complete food composition.

[0022] In some embodiments, the melatonin-containing food composition comprises a nutritionally complete food composition. [Brief explanation of the drawings]

[0023] [Figure 1-1] Reproduction of a questionnaire completed by breeders regarding the quantitative and qualitative characteristics of the coat of registered animals [Figure 1-2] Reproduction of a questionnaire completed by breeders regarding the quantitative and qualitative characteristics of the coat of registered animals [Figure 2] Reproduction of a questionnaire completed by breeders regarding the behavior of registered animals [Figure 3] Graph showing the results over time of coat beauty (top of figure) and shedding (bottom of figure) of enrolled animals when not receiving melatonin or when receiving a daily dose of 10 mg melatonin. The black histogram relates to cats belonging to the control group. The gray histogram relates to the test group supplemented with 10 mg melatonin. The top of Figure 3 shows the effect of supplementation on coat beauty as assessed by pet owners. The bottom of Figure 3 shows the intensity of shedding over the same 6-month period. An earlier (1 month) increase in coat beauty (black arrow) correlates with a decrease in shedding intensity (black arrow). In late December, an increase in shedding is recorded (white arrow). [Figure 4A]Graphs showing changes in hair regrowth in enrolled animals receiving no melatonin or a daily dose of 10 mg melatonin. Figure 4A shows a graph showing (i) ordinate: limited variation; and (ii) abscissa: evaluation number (hours). The solid curve represents the case without melatonin administration. The dashed curve represents the case with 10 mg melatonin administration. [Figure 4B] Graph showing changes in hair regrowth in enrolled animals receiving no melatonin or a 10 mg daily dose of melatonin. Figure 4B shows the mathematically reprocessed data from Figure 4A. Figure 4B shows a graphical representation of hair growth and molting over time, with (i) ordinate: level of variation (arbitrary units); and (ii) abscissa: time. [Figure 5A] Graphs showing the variation in hair loss in enrolled animals receiving no melatonin or a daily dose of 10 mg melatonin. Figure 5A shows a graph showing (i) ordinate: limited variation; (ii) abscissa: evaluation number. The solid curve represents the case without melatonin administration. The dashed curve represents the case with 10 mg melatonin administration. [Figure 5B] Graph showing the variation in hair loss in enrolled animals receiving no melatonin or a daily dose of 10 mg melatonin. Figure 5B shows the mathematically reprocessed data from Figure 5A. Figure 5B shows a graphical representation of hair growth and shedding over time, where (i) ordinate: variation level (arbitrary units); (ii) abscissa: time. [Figure 6A] Graphs showing the variation in coat beauty of enrolled animals receiving no melatonin or a daily dose of 10 mg melatonin. Figure 6A shows a graph showing (i) ordinate: bounded variation; (ii) abscissa: evaluation number (hours). The solid curve represents the case without melatonin administration. The dashed curve represents the case with 10 mg melatonin administration. [Figure 6B]Graph showing the variation in coat beauty of enrolled animals receiving no melatonin or a 10 mg daily dose of melatonin. Figure 6B shows the mathematically reprocessed data from Figure 6A. Figure 6B shows a graphical representation of hair growth and molting over time, where (i) ordinate: variation level (arbitrary units); (ii) abscissa: time. DETAILED DESCRIPTION OF THE INVENTION

[0024] This specification provides a technical solution aimed at improving the quality and quantity of fur in companion animals such as felines and canines.

[0025] Surprisingly, it has now been found that melatonin has the beneficial property of maintaining substantially constant coat quality throughout the year in companion animals.

[0026] More precisely, melatonin has been shown to regulate coat changes throughout the year, mitigating seasonal variations and, in particular, shortening the summer coat period in companion animals.

[0027] Melatonin has been shown to be able to reduce hair shedding (e.g., the severity of hair shedding) or even substantially block hair shedding in companion animals, particularly felines and canines.

[0028] The molt suppression effect of melatonin may in particular lead to earlier improvements in coat aesthetics at the relevant period(s) of the calendar year, more consistent coat aesthetics over time, and therefore improved coat appearance.

[0029] It is also shown herein that melatonin can maintain a substantially constant hair regrowth activity in companion animals throughout the year.

[0030] The present disclosure relates to the use of melatonin to reduce shedding in companion animals, preferably canines or felines, especially felines.

[0031] Melatonin is a natural mammalian hormone that plays an important role in regulating the human circadian cycle. Melatonin is a clinically effective drug and exhibits strong antioxidant properties when used as a sleep aid and as a dietary supplement. It is known in the art that melatonin secretion from the pineal gland plays an important role in mediating the effects of photoperiod changes on reproduction and other seasonal responses.

[0032] The use of melatonin in veterinary medicine has been mentioned for about 30 years, primarily in case reports in publications in the fields of reproductive science and dermatology.

[0033] The properties of melatonin in hair cycle regulation are well known in the art. In humans, melatonin has been shown to promote hair growth (Fischer, 2009, Hautartz, Vol. 60(12): 962-972). Melatonin has been shown to specifically induce cashmere growth by regulating the proliferation of secondary hair follicle stem cells in goats (Zhang et al., 2021, Frontiers in cell and developmental Biology, doi: 10.3389 / fcell.2021.686805). The list of animal species in which melatonin has shown effects on hair growth is quite extensive, including cashmere goats and other caprine species, ferrets, Merino sheep, mink, dogs, and red deer.

[0034] Several studies have reported that melatonin induces or stimulates autumn molting in many animals, including weasels, minks, red deer, and soy roam (Allain et al., 1980, Reprod Nutr Dev, Vol. 2O(1A): 197-201; Lincoln et al., 1985, J Reprod Fertil, Vol. 73: 241-253; Webster et al., 1985, J Reprod Fertil, Vol. 73(1): 255-260).

[0035] To the inventor's knowledge, published case reports on the effects of melatonin on hair coat have not described blinded in vivo studies or in vivo studies that included a comparison of a test group with a control group, e.g., a placebo-treated group. The skin diseases studied were hereditary skin diseases (e.g., pattern hair loss), skin diseases of unknown cause (e.g., recurrent cyclic temporal alopecia), or alopecia in endocrine diseases (e.g., alopecia X).

[0036] In healthy livestock, melatonin is administered as melatonin-containing implants, such as those sold under the brand name Melovine®. These implants are intended to alter the estrous cycle in sheep and promote earlier breeding. These melatonin-containing implants are also used to increase the amount of wool in sheep (e.g., merino, alpaga) and increase wool production.

[0037] In cats, melatonin implants are sometimes used off-label by breeders to suppress the feline estrous cycle for six months. Several other implant devices exist for ferrets, all of which are intended to suppress the estrous cycle.

[0038] To the inventors' knowledge, melatonin has never been used in companion animals, preferably healthy companion animals, to reduce hair shedding.

[0039] For purposes of clarity, and not by way of limitation, the detailed description of the presently disclosed subject matter is divided into the following subsections: 1. Definition; 2. Use of melatonin; 3. Frequency of melatonin administration; 4. Treatment duration; 5. Melatonin-containing compositions; 6. Route of administration of melatonin; and 7. Melatonin dosage.

[0040] definition The terms used herein generally have their ordinary meaning in the art, within the context of this disclosure and within the specific context in which each term is used. Certain terms are discussed below or elsewhere herein to provide additional guidance in describing the compositions and methods of the present disclosure and how to make and use them. The following definitions are provided in this specification, including the claims.

[0041] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a compound" includes a mixture of compounds.

[0042] As used herein, the terms "comprise," "including," "contain," and "containing" are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements does not include only those elements, but may also include other elements not expressly listed or inherent in such process, method, article, or apparatus.

[0043] In the detailed description herein, references to "an embodiment," "one embodiment," "one embodiment," "in various embodiments," etc. indicate that the described embodiment may include a particular feature, structure, or characteristic, but not all embodiments necessarily include the particular feature, structure, or characteristic. Moreover, such phrases do not necessarily refer to the same embodiment. Furthermore, if a particular feature, structure, or characteristic is described in connection with one embodiment, it is believed to be within the knowledge of one skilled in the art to affect such feature, structure, or characteristic in connection with other embodiments, whether or not explicitly stated. After reading the description, it will be apparent to one skilled in the relevant art how to implement the present disclosure in alternative embodiments.

[0044] As used herein, the term "about" or "approximately" means within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 3 or more than 3 standard deviations, in accordance with practice in the art. Alternatively, "about" can mean a range of up to 10%, more preferably up to 5%, and even more preferably up to 1% of a given value.

[0045] The term "melatonin" as used herein means "N-acetyl-5-methoxytryptamine", which is known by IUPAC as "N-(2-5-methoxy-1H-indol-3-yl)ethyl]ethanamide and has the CAS reference number 73-31-4. As used herein, the term "hair loss" refers to the continuous baseline hair / coat loss throughout the year.

[0046] As used herein, the term "molting" or "moulting" in companion animals refers to the intense, regular, seasonal, and cyclical loss of hair / coat, usually every two years, that typically occurs in the spring and fall.

[0047] The expression "effective amount" is to be understood as an amount of melatonin sufficient to reduce hair shedding in a companion animal, e.g., an amount sufficient to reduce the severity and / or duration of hair shedding in said companion animal, e.g., said canine or feline, e.g., said cat.

[0048] As used herein, the terms "reduced molting" or "reducing molting" refer to reducing the occurrence of seasonal hair / coat loss and spreading hair / coat loss more continuously throughout the year.

[0049] As used herein, reducing molting in companion animals can include reducing the level of variation in hair / coat loss throughout the year, and more specifically, the level of variation in hair / coat loss twice a year, in spring and autumn.

[0050] As used herein, reducing the shedding of companion animals can include postponing the time when the semi-annual shedding of the coat occurs.

[0051] As used herein, reducing shedding can also include reducing the amount of hair loss due to shedding, i.e., reducing or decreasing the severity of shedding.

[0052] As used herein, the terms "animal," "pet," or "companion animal" can be used to refer to, for example, domestic or wild animals. In certain embodiments, these terms can refer to canines, including dogs, or felines, including cats.

[0053] As used herein, the term "feline" includes animals, including cheetahs, pumas, jaguars, leopards, lions, lynx, ligers, tigers, panthers, bobcats, ocelots, smilodons, caracals, servals, and pet animals selected from cats. As used herein, cats include wild cats and domestic cats. In certain embodiments, the cat is a domestic cat.

[0054] As used herein, the term "canine" encompasses animals, including companion animals, selected from recognized dog breeds (some of which are further subdivided), including Afghan Hound, Airedale, Akita, Alaskan Malamute, Basset Hound, Beagle, Belgian Shepherd, Bloodhound, Border Collie, Border Terrier, Borzoi, Boxer, Bulldog, Bull Terrier, Cairn Terrier, Chihuahua, Chow Chow, Cocker Spaniel, Collie, Corgi, Dachshund, Dalmatian, Doberman, English Setter, Fox Terrier, German Shepherd, Golden Retriever, and others. These may include: River, Great Dane, Greyhound, Brussels Griffon, Irish Setter, Irish Wolfhound, King Charles Spaniel, Labrador Retriever, Lhasa Apso, Mastiff, Newfoundland, Old English Sheepdog, Papillon, Pekingese, Pointer, Pomeranian, Poodle, Pug, Rottweiler, Saint Bernard, Saluki, Samoyed, Schnauzer, Scottish Terrier, Shetland Sheepdog, Shih Tzu, Siberian Husky, Skye Terrier, Springer Spaniel, West Highland Terrier, Whippet, Yorkshire Terrier, etc.

[0055] As used herein, the term "food composition" or "diet" refers to a material containing proteins, carbohydrates, and / or fats used by an organism to sustain growth, repair, and life processes and to provide energy. Food may contain supplements or additives, such as minerals, vitamins, and seasonings (see Merriam-Webster's Collegiate Dictionary, 10th Edition, 1993, incorporated herein by reference). In certain embodiments, a food composition according to the present disclosure comprises a nutritionally complete food composition that provides the complete and balanced nutritional needs of a companion animal, particularly a feline or canine. Thus, the food composition described herein is a complete food; for example, a complete food is a nutritionally sufficient feed that the animal, e.g., the companion animal, can ingest as its sole feed and can sustain life without additional food (except water). Furthermore, the nutritionally complete food composition does not cause significant changes in the companion animal, i.e., in body weight and / or body condition score (BCS). The food composition may include a carrier, diluent, or excipient. Depending on the intended use, the carrier, diluent, or excipient may be selected to be suitable for use in animals, particularly companion animals such as felines and canines.

[0056] By way of illustration, the food compositions described herein can include, but are not limited to, protein, crude fat, ash, crude fiber, starch, calcium, phosphorus, sodium, chloride, potassium, magnesium, iron, water, copper, manganese, zinc, selenium, vitamin A, vitamin D3, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin B7, vitamin B9, choline chloride, arachidonic acid, W3 fatty acids, or W6 fatty acids.

[0057] As used herein, "dietary supplement" refers to a source of nutrients, substances of nutritional or physiological purpose, or plants and plant preparations, particularly intended to compensate for deficiencies in an animal's normal diet and / or to provide beneficial components or substances to an animal's normal diet. Dietary supplements are typically in the form of capsules, lozenges, tablets, pills, powder packs, or liquids (ampoules, dropper vials). Dietary supplements include compositions containing melatonin and compositions consisting essentially of melatonin, such as aqueous suspensions of melatonin.

[0058] As used herein, the term "animal protein" refers to protein derived from vertebrates such as mammals, poultry, and fish. Animal protein may be derived, for example, from muscle, organs, tendons, or bones. Protein derived from milk or eggs is not considered animal protein.

[0059] As used herein, the term "non-animal protein" refers to a protein that is not an animal protein. Examples of non-animal proteins include plant proteins, algae proteins, egg proteins, milk proteins, microbial proteins, and insect proteins.

[0060] As used herein, the term "starch" refers to a polysaccharide composed of amylose and amylopectin.

[0061] As used herein, the term "fats" refers to lipid compounds, fatty acids and esters of fatty acids such as triglycerides, diglycerides, monoglycerides, and phospholipids.

[0062] The term "palatability" refers to an animal's relative preference for one food over another. Palatability refers to an animal's overall willingness to eat a particular food. Advantageously, but not necessarily, palatability also refers to the ability of the eaten food to satisfy the animal. Whenever an animal shows a preference for, for example, one of two or more foods, the preferred food is more "palatable" or has "enhanced palatability." The relative palatability of one food compared to one or more other foods can be determined, for example, by the relative consumption of the foods or by other suitable preference measures indicating palatability, for example, in a side-by-side free-choice comparison. This can be advantageously determined by standard testing protocols in which the animal has equal access to both foods, such as the so-called "two-bowl test" or "paired test" (see below). Such preference can arise from any of the animal's senses, but typically relates to taste, aftertaste, smell, mouthfeel, and / or texture, among others.

[0063] As used herein, the term "providing" includes selling, supplying, administering, or feeding.

[0064] As used herein, the terms "weight percent" or "weight %" or "by weight" are meant to refer to: (i) the amount by weight of a component / ingredient in a composition as a percentage of the total weight of the composition; or (ii) the amount by weight of a component / ingredient of a material as a percentage of the mass of the final material or product.

[0065] The expression "dry matter (DM) basis" should be interpreted as a way of expressing the concentration of a nutrient or constituent in a feed by expressing the concentration relative to the dry matter content (the concentration remaining after removal of water). Conversely, the expression "as fed" should be interpreted as a way of expressing the concentration of a nutrient or constituent in a feed by expressing the concentration in the as-fed state, including moisture.

[0066] The term "treat" or "treatment" as used herein refers to administering or ingesting a composition according to the present disclosure with the intent to cure, heal, alleviate, relieve, ameliorate, alter, cure, ameliorate, improve, or affect a disorder according to the present disclosure, its symptoms, or to prevent or delay the onset of symptoms, complications, or to prevent or inhibit further progression of the disorder in a statistically significant manner.

[0067] Melatonin Uses A first aspect of the present disclosure relates to the use of melatonin to reduce hair molting in companion animals.

[0068] In one embodiment, the companion animal may be a healthy companion animal, which means a companion animal that is not suffering from any disorder or disease.

[0069] In another embodiment, the companion animal may be one that does not suffer from a disorder or disease that causes hair loss, including companion animals that do not suffer from a skin disorder or disease. According to this embodiment, the companion animal may suffer from any disorder or disease, but does not suffer from a skin disorder or disease.

[0070] In another embodiment, the companion animal may be an unhealthy animal, such as an animal suffering from any disorder or disease, and in such an embodiment, preferably, but not limited to, the unhealthy companion animal does not suffer from a skin disorder or disease.

[0071] In one embodiment, the companion animal is an adult animal, which means an animal that is about 18 months of age or older.

[0072] In another embodiment, the companion animal is a growing animal, which means a companion animal that is at least about 8 months of age, up to about 18 months of age, and it is intended to reduce shedding after the shedding first occurs.

[0073] One embodiment of the present disclosure relates to a method for reducing hair shedding in a companion animal, comprising administering melatonin to the companion animal.

[0074] One embodiment of the present disclosure relates to a method for reducing hair shedding in a companion animal, comprising administering to said companion animal an effective amount of melatonin.

[0075] Another embodiment of the present disclosure relates to a composition comprising melatonin for use in reducing hair molting in companion animals.

[0076] As known in the art, shedding can be easily determined, for example, by brushing the animal to be tested at a specified interval and weighing the amount of hair shed by the brushing step. The interval can be daily, every other week, weekly, every two weeks, or monthly. In most cases, a weekly or every two weeks interval between two consecutive brushing steps is suitable for determining the shedding level. Therefore, in the case of companion animals, a reduction in shedding can be determined by a reduction in the amount of expected seasonal shedding.

[0077] As shown in the examples herein, reduced molting leads to detectable improvements in coat aesthetics.

[0078] Another aspect of the present disclosure relates to the use of melatonin to improve the aesthetics of a companion animal's coat.

[0079] One embodiment of the present disclosure also relates to a method for improving the aesthetics of a companion animal's coat, comprising administering to the companion animal an effective amount of melatonin.

[0080] Another embodiment of the present disclosure relates to a composition comprising melatonin for use in improving the aesthetics of a companion animal's coat.

[0081] As defined herein, the aesthetics of a companion animal's coat, such as a feline, typically includes (i) coat density, (ii) coat color intensity, (iii) coat smoothness, and (iv) coat length.

[0082] The aesthetic improvement can be qualitatively determined by analyzing responses of companion animal owners, which may include animal breeders, to a subjective questionnaire such as that shown in Figure 1. An aesthetic improvement score, consisting of an arbitrary value, can be assessed from the responses to the aesthetic questionnaire. This score can be used to determine the actual positive effect that melatonin has on the aesthetics of companion animal coats.

[0083] As shown in the Examples herein, contrary to what would be expected based on human findings, administration of melatonin to companion animals, such as felines, does not produce detectable changes in the animals' behavior. Melatonin administration has not been found to induce any undesirable effects, such as undesirable effects on the sleep, seasonal rhythms, stress levels, or sexual activity of companion animals.

[0084] Assessment of behavioral changes in companion animals, such as felines, can be qualitatively determined by analyzing responses of companion animal owners, including animal breeders, to a subjective questionnaire such as that shown in Figure 2. Behavioral changes in animals can be determined from responses to the behavioral questionnaire.

[0085] Generally, it is known in the art that melatonin is not toxic even when administered at a dose of 20 mg / kg body weight, which is why it has not been possible to determine the LD50 value for melatonin (the dose that causes death in 50% of administered subjects).

[0086] In a preferred embodiment, the companion animal is a feline or canine, preferably a feline, more preferably the feline is a cat.

[0087] Melatonin administration frequency Melatonin can be administered orally in the form of a food composition, such as a complete food composition, or a dietary supplement.

[0088] A "complete food composition" is sometimes referred to herein as a "nutritionally complete food composition."

[0089] In some embodiments, the appropriate amount of melatonin can be administered in a single administration step, such as orally administered as a food composition, for example, a complete food composition, or as a dietary supplement.

[0090] In some other embodiments, melatonin can be administered twice daily for a suitable treatment period. In some embodiments, melatonin can be administered daily, every other day, every other week, weekly, every two weeks, twice a month, or monthly for a suitable treatment period.

[0091] In some other embodiments, melatonin can be administered daily for the duration of appropriate treatment.

[0092] In some other embodiments, such as those in which the melatonin is contained in a subdermal implant, a suitable amount of melatonin can be administered continuously for a suitable treatment period.

[0093] Treatment period In some embodiments, melatonin can be administered continuously, i.e., throughout the entire calendar year, at a selected frequency.

[0094] In some other embodiments, melatonin can be administered during one or more defined periods during a calendar year (i.e., periods beginning on January 1st of a given calendar year and ending on December 31st of the same calendar year).

[0095] In some other embodiments, melatonin can be administered for a period of about 2 weeks to about 5 weeks, e.g., about 3 weeks to about 4 weeks, where one or two of such treatment periods fall within the same calendar year.

[0096] In embodiments in which melatonin is administered during two treatment periods during a calendar year, (i) the first treatment period preferably begins in January and can be completed within the selected treatment period length, and (ii) the second treatment period preferably begins in June and can be completed within the selected treatment period length. By definition, according to these embodiments, the cumulative duration of the two treatment periods can be less than 12 months. In some of these embodiments, the first treatment period and the second treatment period can have the same duration. In other embodiments, the first treatment period and the second treatment period can have different durations. In some of these embodiments, the first treatment period can be longer than the second treatment period. In other embodiments, the first treatment period can be shorter than the second treatment period.

[0097] Indeed, since the present disclosure is not directed to the alleviation of a companion animal's disorder or disease, but rather to the animal's aesthetics and possibly comfort, the choice of treatment duration may also depend on the decision of the companion animal's owner.

[0098] Melatonin-containing composition In some embodiments, a suitable amount of melatonin can be contained or included in a "dietary supplement," which can include melatonin as a single ingredient in addition to one or more excipient ingredients in a physiologically acceptable vehicle containing melatonin. In one embodiment, the dietary supplement can include an effective amount of melatonin.

[0099] In some other embodiments, the appropriate amount of melatonin can be included in a food composition, e.g., a complete food composition. According to these embodiments, the appropriate amount of melatonin can be specifically provided as a separate ingredient and combined with other ingredients during the manufacturing process of the food composition, e.g., a complete food composition. The food composition, e.g., a complete food composition, can be a wet food composition, a semi-moist food composition, or a dry food composition. In one embodiment, the food composition, e.g., a complete food composition, can include an effective amount of melatonin.

[0100] The present disclosure further relates to food compositions for companion animals, preferably nutritionally complete food compositions for companion animals (such as canines or felines), most preferably for cats. Various melatonin-containing food compositions encompassed by the present disclosure are further described below. In particular, the melatonin-containing food composition can be selected from among wet food compositions, semi-moist food compositions, and dry food compositions, especially from among wet complete food compositions, semi-moist complete food compositions, and dry complete food compositions.

[0101] As used herein, the term "wet food" or "wet food composition" generally refers to a food composition having a moisture content of about 30% or more, typically greater than about 40% by weight, based on the total weight of the food composition. Preferably, a wet food composition may have a moisture content of less than about 90% by weight, based on the total weight of the food composition. Generally, this is the end product of a process that includes a final sterilization step (instead of a drying step). In some embodiments, the wet food may be composed of chunks in chunk form, more specifically, in gravy form. Preferably, the wet food may be in the form of chunks and gravy, chunks in jelly, loaf, mousse, terrine, or bite-sized pieces. "Chunk and gravy" products include preformed meat particles prepared by creating a meat emulsion, forcing the meat emulsion through a muzzle under pressure, and then cooking. The cooked meat product is diced into chunks and ultimately mixed with gravy or sauce. The two ingredients are then filled into a container, usually a can or pouch, seamed or sealed, and sterilized. In contrast to ground loaf, chunk and gravy compositions have physically separated individual chunks (i.e., ground meat and grain pieces) during preparation. These individual particles reside in a gravy-type liquid in the final container. Upon serving, the chunk and gravy product flows out of the can and can be easily mixed with other dry products. While chunk and gravy products allow for better integrity of the individual ingredients, the uneven blending of chunk and gravy products may not be appealing to consumers. Wet food compositions are generally packaged in containers such as cans and are considered "wet" in appearance due to the moisture they contain. Two types of wet compositions are commonly known in the art. The first is known in the art as a "ground loaf." Loaf products are typically prepared by contacting a mixture of ingredients under heat to produce a substantially homogeneous, intracellular honeycomb-type mass or "ground loaf." The ground loaf mass is then filled into cylindrical containers such as cans.When packaged, the ground loaf takes the shape of the container, and when feeding the pet, the ground loaf must be cut. The wet food composition is preferably packaged. In this way, the consumer can identify the ingredients of the food from the packaging and confirm that it is suitable for the particular pet in question. The packaging can be metal, plastic, paper, or card.

[0102] As used herein, the terms "dry food" or "dry food composition" generally refer to a food or composition having a moisture content of less than about 12% by weight relative to the total weight of the food composition, and generally less than about 7% by weight relative to the total weight of the food composition. In some embodiments, dry foods according to the present disclosure can have a moisture content of up to about 12% by weight. In some embodiments, the dry foods can have a moisture content of about 7% or less, e.g., about 5% by weight. In some embodiments, the dry foods have a moisture content of more than about 3% by weight relative to the total weight of the food composition. For example, the examples provided herein show dry foods having a moisture content of about 9.5% by weight relative to the total weight of the food composition. In some embodiments, the dry foods can comprise kibble. For example, but not limited to, kibble includes granules; pellets; pieces of pet food, dehydrated meat, meat analogs, vegetables, and the like, and combinations thereof; and pet snacks such as meat or vegetable jerky, rawhide, and biscuits. Dry food compositions can be produced by mixing and kneading ingredients to create a consistent dough that can be cooked. Generally, this may be the end product of a process that includes an extrusion step followed by a drying step.

[0103] The process of producing dry food is typically carried out by baking and / or extrusion. The dough is typically fed into a machine called an expander and / or extruder, which uses pressurized steam or hot water to cook the ingredients. While in the extruder, the dough is subjected to extreme pressure and high temperature. The dough is then forced through a die (holes of a specific size and shape) and then cut using a knife. The expanded dough pieces are passed through a dryer to form kibble, reducing the moisture content to a specified target and ensuring food stability until consumption. The kibble can then be sprayed with a cocktail of fats, oils, minerals, vitamins, and natural extracts and optionally sealed in a sealed package. Dry food compositions are preferably packaged. In this way, consumers can identify the ingredients of the food from the packaging and confirm that it is suitable for the particular pet in question, i.e., dog. The packaging can be metal, plastic, paper, or card.

[0104] As used herein, the terms "semi-moist food" or "semi-moist food composition" generally refer to a food composition having an intermediate moisture content of about 12% to about 30% relative to the total weight of the food composition. Therefore, such semi-moist food compositions are generally the end product of a process that can achieve a moisture content value intermediate between that of dry food and wet food. In some embodiments, the process can include adding a humectant. In some embodiments, the process can include an extrusion step followed by a superheated steam (SHS) treatment step. In some embodiments, semi-moist food products according to the present disclosure contain more than about 12% by weight of moisture, up to about 30% by weight, relative to the total weight of the food composition. Illustratively, semi-moist food compositions can have a moisture content of about 11% to about 20% by weight, relative to the total weight of the food composition, and / or a water activity of about 0.64 to about 0.75, preferably both.

[0105] According to some embodiments, the moisture content of the animal food composition is (a) weighing a sample of the food composition, thereby obtaining a total weight; (b) heating the sample of step (a) in an oven, e.g., at about 135±2°C for about 240 minutes, until the moisture is completely removed, thereby obtaining a dried sample; (c) weighing the dry feed, thereby obtaining a dry weight; and (d) calculating the difference between the total weight and the dry weight, thereby obtaining the wet weight: Wet weight = (total weight) - (dry weight) The loss on drying can be determined by a loss on drying test method, including:

[0106] In some embodiments, melatonin for use in accordance with the present disclosure can be obtained by conventional chemical synthesis methods, such as those described in Hugel et al. (1994, The New Journal for Organic Synthesis, Vol. 27(1):1-31), which is incorporated herein by reference.

[0107] In some other embodiments, melatonin is obtained from melatonin-containing or melatonin-producing microbial cells, typically melatonin-producing bacteria or melatonin-producing yeast. In particular, different species of both Saccharomyces yeast and non-Saccharomyces yeast can be used to obtain melatonin through alcoholic fermentation processes, as described, for example, in Juhnevica-Radenkova et al. (2020, Comprehensive Reviews in Food Science and Food Safety, doi.org / 10.1111 / 1541-4337.12639), Fernandez-Cruz et al. (2017, Food Chem, Vol. 217: 431-437), and Rodriguez Naranjo et al. (2012, J Pineal Res, Vol. 53(3): 219-224). In some of these embodiments, the melatonin-producing microbial cells may comprise recombinant microbial cells such as melatonin-producing recombinant bacterial cells, including recombinant Escherichia coli (E. coli) cells, or melatonin-producing recombinant yeast cells, including recombinant Saccharomyces cerevisiae cells (both of which are described, for example, in WO 2013 / 127915 or WO 2015 / 032911).

[0108] In some embodiments, melatonin can be derived from the supernatant of cultured melatonin-producing microbial cells, such as the supernatant of cultured melatonin-producing recombinant or non-recombinant bacteria (e.g., E. coli) or cultured melatonin-producing recombinant or non-recombinant yeast (e.g., Saccharomyces cerevisiae).

[0109] In some other embodiments, melatonin can be derived from extracts from cultured melatonin-producing microbial cells, such as extracts from cultured melatonin-producing recombinant or non-recombinant bacteria (e.g., Escherichia coli) or cultured melatonin-producing recombinant or non-recombinant yeast (e.g., Saccharomyces cerevisiae). Yeast extracts can be obtained by a variety of methods well known in the art, including autolysis and hydrolysis-based methods that disrupt yeast cell walls to release the intracellular contents and recover the soluble fraction. Illustratively, an aqueous suspension of yeast cells can be autoclaved and then rapidly cooled on ice, after which the resulting cell debris (i.e., solid fraction) can be removed and the melatonin-containing supernatant recovered.

[0110] Route of melatonin administration According to the present disclosure, melatonin can be administered by a variety of routes: Melatonin can be administered by any suitable route, such as orally, intravenously, rectally, sublingually, mucosally, intranasally, subcutaneously, intramuscularly, or transdermally.

[0111] In preferred embodiments, melatonin can be administered orally, transmucosally, or subcutaneously.

[0112] The administration of melatonin by oral or transmucosal routes has already been widely documented in the art and is therefore part of the background knowledge of the skilled artisan. Furthermore, oral administration of melatonin is exemplified in the examples herein.

[0113] Subcutaneous administration of melatonin can be achieved by (i) subcutaneous injection of a selected dose of melatonin, for example, using a suitable syringe, or (ii) by inserting a subcutaneous implant. Melatonin-containing subcutaneous implants, including those designed for companion animals, are well known in the art. A non-limiting example is the subcutaneous implant sold by Ceva, France, under the brand name Melovine™.

[0114] Melatonin Dosage Those skilled in the art are well aware that the effective amount of a substance such as melatonin can vary depending on several factors. For example, given the present disclosure, a skilled artisan, who may be, for example, a veterinarian, breeder, or clinician, will be able to use their general knowledge to determine or adjust the dosage of melatonin.

[0115] In some embodiments, melatonin can be administered in a daily dose ranging from about 0.5 mg / kg body weight to about 4 mg / kg body weight for a selected treatment period. In such embodiments, for example, a 5 kg cat can receive between about 2.5 and about 20 mg of melatonin per day.

[0116] In some embodiments, melatonin is administered at a dose of about 0.5 mg / kg, about 0.6 mg / kg, about 0.7 mg / kg, about 0.8 mg / kg, about 0.9 mg / kg, about 1 mg / kg, about 1.1 mg / kg, about 1.2 mg / kg, about 1.3 mg / kg, about 1.4 mg / kg, about 1.5 mg / kg, about 1.6 mg / kg, about 1.7 mg / kg, about 1.8 mg / kg, about 1.9 mg / kg, about 2 mg / kg, about 2.1 mg / kg, about 2.2 mg / kg, or about 2.3 mg / kg of body weight during a selected treatment period. g / kg, about 2.3 mg / kg, about 2.4 mg / kg, about 2.5 mg / kg, about 2.6 mg / kg, about 2.7 mg / kg, about 2.8 mg / kg, about 2.9 mg / kg, about 3 mg / kg, about 3.1 mg / kg, about 3.2 mg / kg, about 3.3 mg / kg, about 3.4 mg / kg, about 3.5 mg / kg, about 3.6 mg / kg, about 3.7 mg / kg, about 3.8 mg / kg, about 3.9 mg / kg, or about 4 mg / kg of body weight.

[0117] In other embodiments, melatonin can be administered at a daily dose of about 2 mg / kg body weight for a selected treatment period. In such embodiments, for example, a 5 kg cat can be administered about 10 mg of melatonin per day.

[0118] The present disclosure is further illustrated by, but not limited to, the following examples. [Example]

[0119] A. Materials and Methods A.1. Animals Breeder :Four breeders living under the influence of the same climate (continental climate).

[0120] cat: Four or eight longhair cats per breeder were assigned to each group (one cat per breeder per group, or two per breeder per group for eight cats). Cat cohorts consisted exclusively of Ragdolls, Siberians, and Persians. Each group of cats was approximately equal in terms of (i) male / female gender and (ii) neutered / neutered / intact, with a mean age of 4.4 years. Details of the cat cohorts are shown in Table 1 below.

[0121] [Table 1]

[0122] Cat "Tam" was discontinued on October 10 due to difficulties administering the supplement (per the discontinuation criteria). Cats were continued to be sampled until the end of the study to document the effects of discontinuing supplementation.

[0123] A.2. Inclusion criteria Inclusion criteria were as follows: - No nutritional restrictions or dietary changes will be implemented during the study; - Male / female, spayed / neutered or intact; - Over 18 months old and under 10 years old; - Adequate flea control, deworming medication administered within the past 3 months; - No visible symptoms suggestive of dermatitis (if in doubt, remove the cat from participation or request evaluation by the project manager); and - No systemic disease. BCS: 4, 5, or 6.

[0124] A.3. Non-inclusion criteria The non-inclusion criteria were as follows: - Pregnant or within two months of giving birth; - Clinical evidence of ectoparasitic infection (additional testing should be performed if necessary); - Clinical evidence of bacterial or fungal infection (additional testing should be performed if necessary); - undergoing long-term therapy; - Medications within the past 3 months (any type of medication except antiparasitic drugs); - Use of shampoo within one week prior to participation; - Taking supplements such as essential fatty acids, vitamins, or minerals for improving hair quality within 56 days prior to the start of the study and during the study period; - Comorbid conditions that may worsen during the study period; - Significant changes in circumstances within the past 1.5 months; and - A latitude change of more than 2000 km within the past 1.5 months.

[0125] A.4. Exclusion criteria The exclusion criteria were as follows: - A significant decrease in quality of life, such as a dramatic deterioration of the cat's coat, a significant decrease in BCS, or a loss of 15% or more of body weight; - Significant behavioral changes lasting more than 4 weeks; - Missing two or more doses of the study supplement within a 10-day period; and - Bias from the defined protocol will be assessed by the project manager.

[0126] A.5. Melatonin The assay used melatonin (CAS No. 73-31-4) in powder form, available from Parchem (catalog number 1-800-282-3982). Melatonin powder was dissolved in water and flavoring to a final concentration of 0 mg melatonin in 0.2 ml of liquid (Dose A) or 10 mg melatonin in 0.2 ml of liquid (Dose B) before use.

[0127] A.6. Melatonin Administration and Assay Schedule Each cat began testing on June 21st, the summer solstice.

[0128] Before the first melatonin dose, an initial hair and coat examination was performed, which included brushing the coat (and collecting any loose hair), behavioral observation, and standardized dermoscopic imaging.

[0129] Daily oral administration of 10 mg of melatonin supplements began on June 21 and ended on December 21. A syringe allowed for accurate collection of liquid melatonin from the bottle. The liquid melatonin was tasteless (as confirmed during preliminary evaluation). Oral administration was performed by injecting the contents of the syringe between the gingiva and lip at the level of the canker sore teeth, with the head tilted back for 5 seconds.

[0130] Every two weeks, (i) standardized brushing hair removal and behavioral questionnaires (see Figures 1 and 2 ), and (ii) standardized dermatoscope images were collected.

[0131] A.7. Qualitative and quantitative evaluation of coat Qualitative and quantitative evaluation of the coat was as follows: - reduction in shedding (weight of shedding collected after each brushing session); - Hair density (dermoscopy); - earlier shedding and reduced frequency and duration of shedding (shed weight) assessed by standardized brushing; - Overall coat improvement (full body images of cats and questionnaires); - Primary / secondary hair ratio (dermoscopy); and - Exogenous alopecia condition (trichoscopy).

[0132] A.8. Animal Behavior The assessment of animal behavior consisted of assessing the quality and quantity of sleep, as well as changes / modifications in daily behavior. These parameters were assessed using a questionnaire (see Figure 2).

[0133] A.9. Hair loss assessment (standardized brushing) Using a grooming brush, a designated member of the breeder team groomed four or eight cats recruited from the same breeder throughout the protocol. Hairs shed from brushing were placed in individual bags and stored until sent to the project manager for (i) weighing and (ii) trichoscopy analysis. The following wire grooming brushes were used: a slicker brush with soft pins (for cats and small dogs, brushing surface 7 cm x 5 cm);

[0134] A.10. Dermoscopy Assay Dermoscopy is the gold standard tool for assessing hair growth in humans. Comparing images taken at different times at the same location provides insight into not only hair count but also hair structure. In this disclosure, we extrapolate this technology from humans to pets.

[0135] The device selected for the dermoscopy assay was a wireless 10x to 20x magnification tool that provided interpretable images.

[0136] Two images were taken every two weeks.

[0137] The first image was a full-body image of the cat after brushing. The photographer stood in front of, to the right, or to the left of the cat (always the same side for each cat throughout the study). The angle between the photographer and the cat would be above the animal and 45° to the side. Images were taken under standardized conditions so that they could be compared for each cat over a 6-month period.

[0138] The second image was a "dermatoscope image." Each breeder was equipped with a macroscopic device compatible with any smartphone. Images were taken in the center of the chest (right or left, always on the same side throughout the study). The hair was parted laterally until the skin was visible. Next, the macroscopic device attached to the smartphone was applied to the prepared area, and an image was taken. The location on the skin was marked with a permanent marker to allow for comparison of consecutive images.

[0139] Breeders were the only people required to brush their cats and take gross and dermoscopic images. Breeders received training from the project manager. Because the breeders were the only actors, these assessments were considered standardized and reproducible across groups. Images were immediately sent to the project manager for review, who requested new photos if the image quality did not meet standards.

[0140] A.11. Behavioral Survey Two questionnaires (Figures 1 and 2) were completed every two weeks to gather information on side effects and to ensure there were no effects on reproduction and mood.

[0141] Questionnaire 1 (Figure 1): Interpretation of responses: "Decreased hair loss": assessment of hair loss; "Hair regeneration": Activation of the hair cycle; "Increased coat density": secondary hair growth; "The coat has darkened": a control question to assess the breeder's objectivity (in reality, melatonin has no effect on pigmentation); "The texture of the coat has become smoother": Confirmation of increased density of secondary hairs; "The coat has grown longer": a fake question to assess the overall quality of the breeder's answer (the coat will not grow longer, but the breeder should not know that); and "The coat is more beautiful": This is a subjective response from the breeder, but is an overall assessment.

[0142] Questionnaire 2 (Figure 2): Interpretation of responses 1: General behavioral impact If the answer to 2:1 is "yes," it must be determined whether the cause is due to supplementation. 3: To demonstrate no effect on cat sleep 4: To demonstrate that oral melatonin does not alter food taste 5: Same question as 1, but rephrased to verify the answer to question 1 6: A more nuanced assessment of the effects of melatonin on feline behavior, but on the same topic. 7: Same behavior rating, but specifically grooming 8: Indirect questions to verify answers regarding hairball reduction 9. To ensure that melatonin does not suppress sexual activity 10: Same question as 1 regarding decreased activity.

[0143] B. Results The beauty of the coat and shedding The results in Figure 3 show that there was no hair moulting when 10 mg of melatonin was administered once daily.

[0144] Regarding the reduction in hair loss, hair loss continued from June 21, when melatonin treatment began, until August 21. Thereafter, hair loss decreased until the end of the study in late December.

[0145] The results of the time course of hair regrowth are shown in Figures 4A and 4B, respectively. The results in Figures 4A and 4B show that melatonin administration significantly reduced the time course of hair regrowth, thereby ensuring a more consistent coat thickness.

[0146] Regarding hair loss, the results regarding changes over time are shown in Figures 5A and 5B, respectively.

[0147] Regarding coat aesthetics, the results regarding changes over time are shown in Figures 6A and 6B, respectively.

[0148] The present disclosure showed that without melatonin administration, rapid shedding occurred in early October.

[0149] Melatonin shortened the duration of summer coat formation and at least reduced the severity of the coat molt.

[0150] A daily dose of 10 mg of melatonin did not induce any hair molting.

[0151] Furthermore, with a daily dose of 10 mg of melatonin, secondary hairs remained present throughout both seasons, with a short shedding period in late December.

[0152] The present disclosure also shows that even without melatonin, the coat remains beautiful until the shedding in early October.

[0153] Melatonin promotes an accelerated coat beauty, including a shorter duration of summer coat and an earlier gentle shedding period, which reappears in late December. With melatonin, the coat remains beautiful.

[0154] Melatonin consistently promotes hair growth and significantly reduces hair loss and shedding.

[0155] Furthermore, melatonin maintained consistent coat quality and beauty throughout the year, whereas animals that were not given melatonin experienced a decline in coat quality once they began to molt.

[0156] While the subject matter of the present disclosure and its advantages have been described in detail, it should be understood that various changes, substitutions, and alterations can be made therein without departing from the spirit and scope of the invention, as defined by the appended claims. Furthermore, the scope of the present application is not intended to be limited to the particular embodiments of the processes, machines, manufacture, compositions of matter, means, methods, and steps described herein. As one skilled in the art will readily recognize from the disclosure of the subject matter of the present disclosure, processes, machines, manufacture, compositions of matter, means, methods, or steps, any existing or future-developed means or steps that perform substantially the same function or achieve substantially the same results as the corresponding embodiments described herein can be utilized in accordance with the subject matter of the present disclosure. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.

[0157] Patents, patent applications, publications, product descriptions, and protocols are cited throughout this application, the disclosures of which are incorporated herein by reference in their entireties for all purposes.

Claims

1. Use of melatonin to reduce hair molting in companion animals.

2. The use according to claim 1, wherein the companion animal is a feline, preferably a cat.

3. 3. The use according to claim 1 or 2, wherein the melatonin is administered orally.

4. The use according to any one of claims 1 to 3, wherein the melatonin is contained in a melatonin-containing composition.

5. 5. The use according to any one of claims 1 to 4, wherein the melatonin or the melatonin-containing composition is administered as a dietary supplement.

6. 5. The use according to any one of claims 1 to 4, wherein the melatonin or the melatonin-containing composition is included in a complete pet food composition.

7. 3. The use according to claim 1 or 2, wherein the melatonin is administered by subcutaneous, transdermal or intradermal route.

8. 8. The use according to any one of claims 1 to 7, wherein the melatonin is contained in an extract from a melatonin-producing microorganism, preferably in an extract from a melatonin-producing yeast.

9. 9. The use according to any one of claims 1 to 6 and claim 8, wherein the melatonin is administered daily.

10. 10. The use according to any one of claims 1 to 6 and claims 8 to 9, wherein the melatonin is administered orally in a daily dose ranging from about 0.5 mg / kg body weight to about 4 mg / kg body weight.

11. 10. The use according to any one of claims 1 to 6 and claims 8 to 9, wherein the melatonin is administered orally in a daily dose of about 2 mg / kg body weight.

12. 1. A method for reducing hair molting in companion animals, comprising administering melatonin.

13. 13. The method of claim 12, wherein the companion animal is a feline, preferably a cat.

14. 13. The method of claim 12, wherein the melatonin is administered orally.

15. 13. The method of claim 12, wherein the melatonin is included in a dietary supplement or a complete food composition.

16. 13. The method of claim 12, wherein the melatonin is administered daily.

17. 13. The method of claim 12, wherein the melatonin is orally administered in a daily dose ranging from about 0.5 mg / kg body weight to about 4 mg / kg body weight of the companion animal.

18. 13. The method of claim 12, wherein the melatonin is administered orally in a daily dose of about 2 mg / kg body weight.

19. A melatonin-containing food composition for companion animals, selected from a wet complete food composition, a semi-moist complete food composition, and a dry complete food composition.

20. 20. The melatonin-containing food composition of claim 19, comprising a nutritionally complete food composition.

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