JP2023507372A - Compositions containing specific ratios of soluble and insoluble fibers for use in treating anxiety and the like - Google Patents

Abstract

Compositions and methods for treating anxiety or stress in animals are disclosed. Compositions and methods for reducing or preventing elevated 4-EPS levels are disclosed. Compositions and methods are disclosed for promoting the growth of beneficial microorganisms and inhibiting the growth of harmful microorganisms in an animal's microbiota. The method includes administering to the animal an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber. The composition comprises effective amounts of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble to soluble fiber. [Selection drawing] Fig. 1

Description

The microbial toxin 4-ethylphenyl sulfate (4-EPS) is a metabolite produced by intestinal bacteria. 4-EPS, among other microbial metabolites, enters the systemic circulation. Elevated levels of 4-EPS in the blood, especially in dogs, are associated with stress, anxiety, brain injury, and other behavioral problems. Lowering 4-EPS levels has been shown to reduce symptoms of stress and anxiety.

Anxiety in dogs (anxiety disorder) is a response to fear, agitation, or anxiety when a dog anticipates a threat or fearful situation. Some dogs experience disproportionate levels of anxiety. Anxiety can develop into anxiety disorders and lead to behavioral and other problems. Some dogs experience generalized anxiety disorder, exhibiting fear responses in a wide range of situations to which "normal" pets would be difficult to respond. Anxiety can take the form of one of a variety of anxiety disorders such as generalized anxiety disorder, hyperstimulus anxiety, separation anxiety, withdrawal, noise phobia, among others.

Causes include genetic factors, prenatal and neonatal stressors, mother-infant separation, lack of socialization, unfamiliarity, or previous unpleasant consequences of exposure to the stimulus (or similar stimuli). can be considered. The most common causes are fear, isolation, and aging. Fear-related anxiety can be triggered by loud noises, strange people or animals, visual stimuli, new or unfamiliar surroundings, specific situations, among others. Age-related anxiety affects older dogs and can be associated with cognitive dysfunction syndrome (CDS). Separation anxiety is a unique anxiety that arises from a pet's inability to find comfort when separated from the family. About 14% of dogs have separation anxiety. Some separation anxiety can be the result of dysfunctional attachments as puppies age and mature. In some cases, separation anxiety can occur when it involves changes in home or daily routines, while other separation anxiety may have an underlying anxiety state, along with other behavioral problems such as phobias. could be.

Anxiety is characterized by destructive behavior (especially to exits or belongings), distressed vocalizations, house soiling, salivation, walking, fidgeting, restlessness, anorexia, and repetitive or compulsive behavior. can lead to In some cases, anxiety can contribute to aggressive behavior.

Common symptoms of anxiety in dogs include aggression, urinating and defecation in the home, drooling, rapid breathing, disruptive behavior, depression, excessive barking, pacing, fidgeting, and repetitive or obsessive behavior. include. Different dogs exhibit different symptoms and combinations of symptoms when suffering from anxiety.

Dog stress is a dog's reaction to being asked to change or adapt, usually manifesting as tension and pressure. Stress in dogs can cause feelings of fear, agitation, hyperactivity, nervousness, irritability, or tantrums. Negative stress, excessive stress, and chronic stress can adversely affect behavior, health, and overall health. Stress causes disease, suppresses the immune system, triggers unwanted behavior, and increases arousal and the likelihood of aggressive behavior.

Causes of stress in dogs include grief, exposure to conflict, excessive or inadequate stimulation, overcrowding, environmental changes (increase in schedules, people, animals, noise), disciplinary training, and inadequate social time, among others. , including frightening events, neglect, frustration, and uncertainty.

Tell them that dogs are stressed in a variety of ways. Indicators that a dog is stressed include dilated pupils, firmness around the eyes, cetacean/crescent eyes, yawning, lip/nose licking, rapid breathing, excessive salivation, smiling, bruxism, Includes bulging cheeks, baring teeth, wrinkled muzzle, ears set back or erect. Other indicators are tense body, stretching, excessive hair loss, little or no movement, low posture, backward weight shifting, trembling/shaking, exposed penis, sweaty legs, stiff eyebrows. , barking, growling, howling, and snorting. Dogs' behavior often changes when they are stressed. Behaviors commonly triggered by stress include, among others, fidgeting, poor or hypersomnia, jumpiness/irritability, tantrums, excessive self-grooming, disruptive behavior, anorexia, obsessive/impulsive behavior, and inability to concentrate. , hyperactivity, increased voiding, vomiting and diarrhea.

A need exists for methods and compositions for reducing elevated levels of 4-EPS in dogs. There is a need for methods and compositions for treating or reducing elevated levels of severity of anxiety in dogs. There is a need for methods and compositions for treating or reducing elevated levels of severity of stress in dogs.

Methods of treating anxiety or stress in animals are provided. The method includes administering to the animal an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber.
Methods of reducing elevated 4-EPS levels in an animal with elevated 4-EPS levels are provided. The method includes administering to the animal an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber.
Methods are provided for preventing elevated levels of 4-EPS in animals. The method comprises administering to an animal at risk of elevated 4-EPS levels an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber.
Methods are provided for promoting the growth of beneficial microorganisms and inhibiting the growth of non-beneficial microorganisms in an animal's microbiota. The method includes administering to the animal an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber.
Compositions are provided for treating anxiety or stress in animals. The composition comprises an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber.
Compositions are provided for reducing elevated 4-EPS levels in an animal with elevated 4-EPS levels. The composition comprises an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber.
Compositions are provided for preventing elevated 4-EPS levels in an animal. The composition comprises an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber.
Compositions are provided that promote the growth of beneficial microorganisms and inhibit the growth of non-beneficial microorganisms in an animal's microbiota. The composition comprises an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber.

FIG. 1 shows data from the experiments described in Example 1, in which 4-EPS levels were measured in dogs after being pre-fed, control, or given a test food composition. Relative blood levels of log 4-EPS after each 30-day period are shown for pre-feeding, control/test, washout (pre-feeding), and post-crossover (control/test) treatments. Results show that pre-feeding resulted in a significant increase in 4-EPS levels compared to treatment food (control/test) (P<0.0001).

The following description of the preferred embodiments is merely exemplary in nature and is not intended to limit the invention, its application, or uses in any way.
As used in this invention and in the appended claims, the singular forms "a,""an," and "the" include plural forms unless the context clearly dictates otherwise.

As used herein, the term "companion animal" includes any non-human animal suitable to be kept as a pet by humans, including, but not limited to, dogs, cats, rabbits and rodents. . Certain embodiments are therapeutic formulations and methods for dogs and/or cats. In one particular aspect, formulations and methods for the treatment of dogs are provided.

The term "dog" includes dogs that are companion animals, such as Canis familiaris, working dogs, and the like. The term "dog" is synonymous with the term "canine."

The term "cat" includes a companion animal known as a domestic or house cat or Felis domesticus. The term "cat" is synonymous with the term "feline."

The terms "highly soluble fiber" and "soluble fiber" can be used interchangeably.

The terms "low-soluble fiber" and "insoluble fiber" may be used interchangeably.

The terms: n-3 fatty acids and omega-3-fatty acids can be used interchangeably.

Methods are provided for treating anxiety and stress in animals, particularly companion animals such as dogs or cats. The method includes administering to the animal an effective amount of n-3 fatty acids, an antioxidant, and a combination of insoluble and soluble fiber in an effective ratio of insoluble to soluble fiber. The composition comprises an effective amount of n-3 fatty acids, an antioxidant, and an effective ratio of insoluble to soluble fiber insoluble and soluble fiber. In some embodiments, the effective amount of n-3 fatty acids is 0.6-0.9% of the daily nutritional intake, in some embodiments from 0.65 to 0.65% of the daily nutritional intake. 0.85%, in some embodiments 0.70-0.80% of the daily nutrient intake, in some embodiments 0.72-0.79% of the daily nutrient intake is. In some embodiments, the effective amount of antioxidants includes a combination of vitamin C and vitamin E. In some embodiments, in the combination of vitamin C and vitamin E, the effective amount of vitamin C is at a level greater than 400 ppm of the daily nutritional intake, and in some embodiments at a level of greater than 450 ppm of the daily nutrient intake, in some embodiments at a level of greater than 475 ppm of the daily nutrient intake, and in some embodiments at a level of greater than 480 ppm of the daily nutrient intake Yes, and in some embodiments at a level of greater than 490 ppm of the daily nutrient intake, and in some embodiments at a level of greater than 500 ppm of the daily nutrient intake, and In some embodiments, the level is greater than 550 ppm of daily nutrient intake. In some embodiments, in combination with vitamin C and vitamin E, the effective amount of vitamin E is a level greater than 1000 IUK of daily nutritional intake, and in some embodiments The effective amount is a level of greater than 1200 IUK of daily nutrient intake, and in some embodiments the effective amount of vitamin E is a level of greater than 1300 IUK of daily nutrient intake, and In some embodiments, the effective amount of vitamin E is a level greater than 1400 IUK of the daily nutritional intake, and in some embodiments the effective amount of vitamin E is levels above 1500 IUK. In some embodiments, the combination of insoluble fiber and soluble fiber is such that the ratio of insoluble fiber to soluble fiber (amount of insoluble fiber/amount of soluble fiber) is from 2.0 to 3.0 in some embodiments. and in some embodiments a ratio in the range 2.1 to 2.9 and in some embodiments a ratio in the range 2.2 to 2.8 and in some embodiments a ratio in the range of 2.3 to 2.7 and in some embodiments a ratio in the range of 2.4 to 2.6 and in some implementations In the form of 4.0% or more of the daily nutrient intake, in some embodiments 4.5% or more of the daily nutrient intake, in a ratio ranging from 2.4 to 2.5 In some embodiments, 4.6% or more of the daily nutrient intake, in some embodiments 4.7% or more of the daily nutrient intake, in some embodiments, 4.7% or more of the daily nutrient intake 4.8% or more of the daily intake, in some embodiments 4.9% or more of the daily nutrient intake, in some embodiments 5.0% or more of the daily nutrient intake provided in

"Daily Nutrient Intake" and "Total Daily Nutrient Intake" mean the dry matter intake per day. That is, water weight is not included in the calculation of daily nutrient consumption. To the extent that food and food ingredients contain water/moisture, dry matter refers to anything contained in a sample other than water, including protein, fiber, fat, minerals, and the like. The weight of dry matter is the total weight minus the weight of water. Dry matter intake per day is calculated as total nutrient intake per day excluding all water. For example, the amount of an ingredient representing a particular percentage of the daily nutrient intake is the ratio of the total amount of dry matter consumed daily (i.e., excluding all water) to the total amount of dry matter ) means the amount of that ingredient. Those skilled in the art will readily recognize and understand amounts of dry matter, weight of dry matter, and nutrient amounts and percentages expressed as a percentage of dry matter. Wet, moist, or dry foods generally contain a fixed amount of water, so the water component of such foods is excluded when calculating daily dry matter intake. Water is excluded in order to calculate the total daily nutrient intake, which is the dry matter intake per day. To calculate the percentage of an ingredient in the total daily intake on a dry matter basis, remove the water from the total intake to give the total daily dry matter intake, and the percentage of the ingredient is the ingredient present as dry matter. Calculate based on quantity.

A composition useful in the method can be a pet food composition, such as a dog food composition. Alternatively, n-3 fatty acids, antioxidants, and insoluble and soluble fibers may be administered as supplements, treats, or toys, or otherwise provided to animals for their daily nutritional intake. It does not have to be incorporated into the food served.

In some preferred embodiments, the animal is a dog and the method comprises administering to the dog an effective amount of n-3 fatty acids, antioxidants, and insoluble and soluble fibers. An effective amount of n-3 fatty acids administered to a dog per day is 0.6-0.9% of the daily nutritional intake, in some embodiments 0.65 of the daily nutritional intake. ~0.85%, in some embodiments 0.70-0.80% of the daily nutrient intake, in some embodiments 0.72-0.79 of the daily nutrient intake %.

Effective amounts of antioxidants include a combination of vitamin C and vitamin E, and in some embodiments of the combination: an effective amount of vitamin C based on daily nutritional intake is at a level greater than 400 ppm , in some embodiments at levels greater than 450 ppm, in some embodiments at levels greater than 475 ppm, in some embodiments at levels greater than 480 ppm, in some embodiments a level greater than 490 ppm, in some embodiments a level greater than 500 ppm, and in some embodiments a level greater than 550 ppm; Effective amounts are at levels above 1000 IUK, in some embodiments at levels above 1200 IUK, in some embodiments at levels above 1300 IUK, in some embodiments at levels above 1400 IUK. Yes, and in some embodiments, levels above 1500 IUK. The combination of insoluble fiber and soluble fiber is such that the ratio of insoluble fiber to soluble fiber (amount of insoluble fiber/amount of soluble fiber) is, in some embodiments, a ratio ranging from 2.0 to 3.0. In some embodiments, a ratio in the range of 2.1 to 2.9, in some embodiments, a ratio in the range of 2.2 to 2.8, and in some embodiments, from 2.3 to with a ratio in the range of 2.7, in some embodiments with a ratio in the range of 2.4 to 2.6, and in some embodiments with a ratio in the range of 2.4 to 2.5 , based on daily nutrient intake, 4.0% or more, in some embodiments 4.5% or more, in some embodiments 4.6% or more, in some embodiments 4 .7% or more, in some embodiments 4.8% or more, in some embodiments 4.9% or more, in some embodiments 5.0% or more . Preferably, the composition is a dog food composition comprising an effective daily amount of n-3 fatty acids, antioxidants such as a combination of vitamins C and E, and a combination of soluble and insoluble fibers.

Compositions and methods are provided for treating anxiety and stress in animals, particularly companion animals such as cats or dogs. The compositions and methods are useful for treating symptoms of anxiety or stress in an animal in need thereof. The compositions and methods are useful for treating symptoms of anxiety or stress in such animals with elevated 4-EPS levels. The compositions and methods are useful for reducing elevated 4-EPS levels in companion animals, particularly animals with elevated 4-EPS levels, such as dogs. In some embodiments, compositions and methods for treating canine anxiety or canine stress in dogs. Compositions and methods are provided that promote the growth of desirable beneficial microorganisms in the gut microbial population and inhibit the growth of undesirable unhealthy microorganisms in the gut microbial population.

As used herein, the term "treatment" refers to the elimination, reduction in severity, or prevention of one or more symptoms.

As used herein, the term "anxiety" refers to anxiety disorders, anxiety disorders, and symptoms of anxiety disorders and anxiety disorders.

As used herein, the term "stress" refers to stress, stress disorders, and symptoms of stress and stress disorders.

As used herein, the term "treatment" with respect to anxiety refers to therapeutic and/or prophylactic activity. In dogs with symptoms of anxiety, treatment of canine anxiety refers to eliminating symptoms, halting or slowing the progression of symptoms, reducing the severity of symptoms and preventing symptoms. Treatment that initially eliminates, halts, slows progression, or reduces severity of symptoms may be continued, and continued treatment further eliminates, halts, slows progression, or reduces severity of symptoms, and/or or prevent the recurrence or development of symptoms, or reduce the severity of further development of symptoms. In some embodiments, the dog may be identified as having symptoms of anxiety prior to treating the dog for anxiety. In some embodiments, dogs can be treated for anxiety without identifying anxiety symptoms prior to treatment. In some embodiments, prior to treatment for anxiety, the dog may be identified as having or being predisposed to develop anxiety. In some embodiments, prior to treatment for anxiety, dogs may be identified as having elevated 4-EPS levels.

As used herein, the term "treatment" with respect to stress and stress disorders refers to therapeutic and/or prophylactic activity. In dogs with symptoms of stress or stress disorders, treating canine stress refers to eliminating symptoms, halting or inhibiting the progression of symptoms, reducing the severity of symptoms and preventing symptoms. Treatment that initially eliminates, halts, slows progression, or reduces severity of symptoms may be continued, and continued treatment further eliminates, halts, slows progression, or reduces severity of symptoms, and/or or prevent the recurrence or development of symptoms, or reduce the severity of further development of symptoms. In some embodiments, the dog may be identified as having symptoms of stress or a stress disorder prior to treating the dog for stress. In some embodiments, dogs can be treated for stress or stress disorders without identifying anxiety symptoms prior to treatment. In some embodiments, prior to treatment for stress or stress disorder, the dog may be identified as having stress or stress disorder or predisposed to developing stress or stress disorder. In some embodiments, prior to treatment for stress or stress disorders, dogs can be identified as having elevated 4-EPS levels.

As used herein, the term "treatment" with respect to promoting the growth of beneficial microorganisms and inhibiting the growth of harmful microorganisms refers to therapeutic and/or prophylactic activity. Halting the levels of beneficial and harmful microorganisms or promoting the growth of beneficial microorganisms and inhibiting the growth of harmful microorganisms in dogs with reduced levels of beneficial microorganisms and elevated levels of harmful microorganisms It is a treatment to Dogs identified as predisposed to inhibit beneficial microbial growth and promote harmful microbial growth prior to initiation of treatment. In an animal with increased levels of harmful microorganisms and decreased levels of beneficial microorganisms, it initially promotes the growth of beneficial microorganisms, inhibits the growth of harmful microorganisms, increases the levels of beneficial microorganisms, reduces harmful microorganisms It is a treatment that lowers the level of harmful microorganisms to a more healthy balance and then maintains the level with continuous treatment. In some embodiments, prior to treating the dog for stress, the dog may be identified as having increased levels of harmful microorganisms and decreased levels of beneficial microorganisms. In some embodiments, dogs can be treated without identifying increased levels of harmful microorganisms and decreased levels of beneficial microorganisms in the animal.

As used herein, the terms "treating elevated 4-EPS", "treating against elevated 4-EPS", "treating elevated 4-EPS" refer to refers to therapeutic and/or prophylactic activity. In dogs with elevated 4-EPS levels, "treating elevated 4-EPS", "treating against elevated 4-EPS", and "treating elevated 4-EPS" Refers to level reduction. Treatment can reduce elevated 4-EPS levels to normal, non-elevated levels, or reduced elevated 4-EPS levels. Following reduction of elevated 4-EPS levels, treatment may prevent elevated 4-EPS levels or lessen the severity of further elevated 4-EPS levels. In dogs without elevated 4-EPS levels, "treating elevated 4-EPS", "treating against elevated 4-EPS", and "treating elevated 4-EPS" are defined as 4-EPS Refers to stopping or lowering levels and preventing the occurrence of elevated 4-EPS levels or reducing the severity of the occurrence of elevated 4-EPS levels. In some embodiments, prior to treatment for 4-EPS, dogs can be identified as having elevated 4-EPS by measuring 4-EPS levels. In some embodiments, dogs can be treated for elevated 4-EPS without measuring 4-EPS levels prior to treatment. In some embodiments, prior to treating 4-EPS, the dog can be identified as predisposed to elevated 4-EPS. Dogs identified as predisposed to elevated 4-EPS may have elevated 4-EPS at the time of treatment, in which case the treatment is therapeutic or they do not have elevated 4-EPS. treatment may be prophylactic, in which case treatment may be given without determining 4-EPS levels. In some embodiments, a dog can be identified as predisposed to elevated 4-EPS prior to initiating treatment with or without measuring 4-EPS levels.

As used herein, "effective amount," "effective amount," and like terms refer to a specific biological result, i.e., when delivered in combination with an effective ratio of insoluble and soluble fibers. , refers to the amount of n-3 fatty acids and antioxidants effective to achieve elevated 4-EPS levels, treatment of anxiety, stress, and levels of beneficial and harmful microbes in the microbiome. In certain embodiments, administration of a composition comprising an effective amount of n-3 fatty acids and antioxidants in combination with an effective ratio of insoluble and soluble fibers is carried out for a period of time sufficient to effect treatment. be done. In certain embodiments, the method comprises a composition comprising an effective amount of n-3 fatty acids and antioxidants in combination with an effective ratio of insoluble and soluble fibers for a period of time sufficient to provide effective treatment and maintenance. Including administration and consumption of things. The effective amount depends on the dog's ideal weight, age, sex, activity level, metabolizable energy of the composition, and the frequency of the composition given, e.g., once, twice, or three times a day, and the dog's may be based on a number of factors, including other compositions provided for. In some embodiments, an effective amount refers to the amount of n-3 fatty acids and antioxidants combined with effective ratios of insoluble and soluble fiber administered based on total daily nutrient intake. In some embodiments, an effective amount refers to a pet food comprising n-3 fatty acids and antioxidants combined with effective ratios of insoluble fiber and soluble fiber on a dry matter basis to total daily nutritional intake. Thus, a suitable amount of food to meet all of the daily nutritional and energy requirements for a canine subject comprises, on a dry matter basis, an effective amount of n-3 fatty acids and antioxidants, an effective proportion of insoluble fiber and soluble fiber. Contains in combination with fiber.

As used herein, "effective ratio of insoluble fiber to soluble fiber" and similar terms refer to a specific biological result, i.e., effective amounts of n-3 fatty acids and antioxidants delivered in combination. When the ratio of insoluble fiber to soluble fiber in the daily diet was effective to achieve elevated 4-EPS levels, treatment of anxiety, stress, and levels of beneficial and harmful microbes in the microbiome, Point. The effective ratio is determined by the dog's ideal weight, age, sex, activity level, metabolizable energy of the composition, and frequency of the composition given, e.g., once, twice, or three times a day, and the dog's may be based on a number of factors, including other compositions provided for. The effective ratio can be expressed as a number calculated by dividing the amount of insoluble fiber by the amount of soluble fiber (ie, amount of insoluble fiber/amount of soluble fiber).

In certain embodiments, administration of a composition comprising effective amounts of n-3 fatty acids and antioxidants in combination with an effective ratio of insoluble fiber and soluble fiber to insoluble fiber and soluble fiber is effective for treatment. is conducted for a sufficient period of time. In certain embodiments, the method comprises administering an effective amount of n-3 fatty acids and antioxidants for a period of time sufficient to provide effective treatment and maintenance. Including the administration and consumption of compositions containing a combination of ratios.

In some embodiments, the effective amount of n-3 fatty acids is 0.6-0.9% of the daily nutritional intake, in some embodiments from 0.65 to 0.65% of the daily nutritional intake. 0.85%, in some embodiments 0.70-0.80% of the daily nutrient intake, in some embodiments 0.72-0.79% of the daily nutrient intake is.

In some embodiments, the effective amount of antioxidants includes a combination of vitamin C and vitamin E. In some embodiments, in the combination of vitamin C and vitamin E, the effective amount of vitamin C is at a level greater than 400 ppm of the daily nutritional intake, and in some embodiments at a level of greater than 450 ppm of the daily nutrient intake, in some embodiments at a level of greater than 475 ppm of the daily nutrient intake, and in some embodiments at a level of greater than 480 ppm of the daily nutrient intake Yes, and in some embodiments at a level of greater than 490 ppm of the daily nutrient intake, and in some embodiments at a level of greater than 500 ppm of the daily nutrient intake, and In some embodiments, the level is greater than 550 ppm of daily nutrient intake. In some embodiments, in combination with vitamin C and vitamin E, the effective amount of vitamin E is a level greater than 1000 IUK of daily nutritional intake, and in some embodiments The effective amount is a level of greater than 1200 IUK of daily nutrient intake, and in some embodiments the effective amount of vitamin E is a level of greater than 1300 IUK of daily nutrient intake, and In some embodiments, the effective amount of vitamin E is a level greater than 1400 IUK of the daily nutritional intake, and in some embodiments the effective amount of vitamin E is levels above 1500 IUK.

In some embodiments, the combination of insoluble fiber and soluble fiber is such that the ratio of insoluble fiber to soluble fiber (amount of insoluble fiber/amount of soluble fiber) is from 2.0 to 3.0 in some embodiments. and in some embodiments a ratio in the range 2.1 to 2.9 and in some embodiments a ratio in the range 2.2 to 2.8 and in some embodiments a ratio in the range of 2.3 to 2.7 and in some embodiments a ratio in the range of 2.4 to 2.6 and in some implementations In the form of 4.0% or more of the daily nutrient intake, in some embodiments 4.5% or more of the daily nutrient intake, in a ratio ranging from 2.4 to 2.5 In some embodiments, 4.6% or more of the daily nutrient intake, in some embodiments 4.7% or more of the daily nutrient intake, in some embodiments, 4.7% or more of the daily nutrient intake 4.8% or more of the daily intake, in some embodiments 4.9% or more of the daily nutrient intake, in some embodiments 5.0% or more of the daily nutrient intake provided in

In some preferred embodiments, the animal is a dog and the method comprises a combination of an effective amount for a dog of n-3 fatty acids, an antioxidant such as vitamin C and vitamin E, and an effective ratio of insoluble and soluble fibers. including administering The combination may be administered as a pet food composition, such as a dog food composition, or as a supplement, treat or toy, or otherwise incorporated into the food given to the animal for its daily nutritional intake. may In some embodiments, the effective amount of n-3 fatty acids is 0.6-0.9% of the daily nutritional intake, in some embodiments from 0.65 to 0.65% of the daily nutritional intake. 0.85%, in some embodiments 0.70-0.80% of the daily nutrient intake, in some embodiments 0.72-0.79% of the daily nutrient intake is.

A "food", "food composition", or "pet food composition" can, in some embodiments, be a nutritionally complete meal for an animal, such as a dog, to which it is fed.

As used herein, "ingredient" refers to any element of the composition.

The term "nutrient" refers to a substance that provides nutrition. In some cases, an ingredient may include one or more "nutrients," for example, a composition may include corn, which contains key nutrients including both protein and carbohydrate.

The food composition can be provided to animals, including but not limited to pets, in the form of pet food. Various types of commonly known pet foods are available to pet owners. Pet food options include, but are not limited to, wet pet food, semi-moist pet food, dry pet food, and pet treats. Wet pet food generally has a moisture content greater than about 65%. Semi-moist pet foods generally have a moisture content of about 20% to about 65% and may contain humectants, potassium sorbate, and other ingredients to prevent microbial growth (bacteria and mold). Dry pet food, including but not limited to food kibble, generally has a moisture content of less than about 15%. Pet treats are typically semi-moist, chewable treats, dry treats in any number of forms, chewable bones or baked, extruded or punched treats, confection treats. , or other types of treats known to those skilled in the art.

As used herein, the term "kibble" or "food kibble" refers to certain pellet-like components of animal feeds, such as dog and cat feeds. In some embodiments, the food kibble has less than 15% by weight moisture content or moisture. Food kibble can range in texture from hard to soft. Food kibble can range in internal structure from expanded to dense. Food kibble can be formed by an extrusion process or a baking process. In non-limiting examples, the food kibble can have a uniform internal structure or a varying internal structure. For example, a food kibble may include a core and a coating to form a coated kibble. It should be understood that when the term "kibble" or "food kibble" is used, it can refer to uncoated kibble or coated kibble.

As used herein, the term "extrusion" or "extrusion" refers to the process of sending a pretreated and/or prepared mixture of ingredients through an extruder. In some embodiments of extrusion, the food kibble is formed by an extrusion process in which a kibble dough comprising a mixture of wet and dry ingredients can be extruded under heat and pressure to form the food kibble. Any type of extruder can be used, including but not limited to single screw extruders and twin screw extruders. Combinations and mixtures of the sources, ingredients, and ingredient lists set forth below are also contemplated and are listed within the scope of the specification.

As intended herein, compositions are meant to include, but are not limited to, nutritionally complete and balanced animal food compositions. A "nutritionally complete diet" is a diet that may contain sufficient nutrients to maintain normal health in a healthy dog. Complete nutritionally balanced pet food compositions, eg for dogs, are well known to those skilled in the art. For example, materials such as nutrients and ingredients suitable for nutritionally complete and balanced animal feed compositions, and recommended amounts thereof, are found, for example, in the Official Publication of the Association of American Feed Control Officials, Inc.; (AAFCO), Atlanta, Ga. , (2012).

In feeding a dog a diet containing effective amounts of n-3 fatty acids and antioxidants in combination of insoluble and soluble fiber in an effective ratio of insoluble to soluble fiber, a preferred method comprises in an effective ratio of insoluble fiber to soluble fiber and providing a food product containing an effective amount of n-3 fatty acids and antioxidants. In other embodiments, feeding a dog a diet comprising effective amounts of n-3 fatty acids and antioxidants in combination with insoluble and soluble fiber in an effective ratio of insoluble to soluble This is achieved by administering oxidants and insoluble fiber and insoluble fiber as supplements or treats. effective amounts of n-3 fatty acids combined with insoluble and soluble fiber in an effective ratio of insoluble to soluble fiber, whether delivered in the pet food composition or separately as a supplement or in a treat; In any event, feeding a dog a diet containing antioxidants is feeding the dog a diet containing effective amounts of n-3 fatty acids and antioxidants in combination with effective ratios of insoluble and soluble fibers. it is conceivable that.

As used herein, the term "supplement(s)" includes, but is not limited to, feeds that are used with another feed to improve the nutritional balance or overall diet performance of an animal. As a supplement, including but not limited to, given undiluted as a supplement to other feed, to provide free choice by other parts of the animal's ration available separately, or diluted and mixed with the animal's normal feed Included are compositions that are used to make a complete bait. For example, AAFCO guidelines include a discussion of supplements in the American Association of Feed Control Officials (AAFCO), Atlanta, Ga (2012). Supplements can be in a variety of forms including, for example, powders, liquids, syrups, pills, encapsulated compositions, and the like.

The diet contains effective amounts of n-3 fatty acids and antioxidants combined with insoluble and soluble fiber in an effective ratio of insoluble to soluble fiber to reduce elevated 4-EPS levels in animals such as cats or dogs. . A diet containing effective amounts of n-3 fatty acids and antioxidants in combination with insoluble and soluble fiber in an effective ratio of insoluble to soluble fiber is useful for treating anxiety in dogs. A diet containing effective amounts of n-3 fatty acids and antioxidants in combination with insoluble and soluble fiber in an effective ratio of insoluble to soluble fiber is useful for treating stress in dogs. A diet containing effective amounts of n-3 fatty acids and antioxidants, in combination with insoluble and soluble fiber in an effective ratio of insoluble to soluble fiber, is beneficial to the animal's microbiome, particularly the microbiome of the animal's gastrointestinal track, and particularly It is useful for promoting the growth of beneficial microorganisms and inhibiting the growth of harmful microorganisms in animals, cats or dogs.

Compositions and formulations

Application of the methodology outlined above showed that there is a predisposition to elevated 4-EPS levels, and therefore an increased risk of developing anxiety, an increased risk of developing anxiety stress, and an increase in the canine microbiota, especially in the gut microbiota. Effective amounts of n-3 fatty acids and antioxidants that provide significant benefits to animals identified as being at high risk of inhibiting the growth of beneficial microorganisms and promoting the growth of harmful microorganisms, particularly dogs and cats. , were able to identify combinations of insoluble and soluble fibers in effective proportions. In some embodiments, effective amounts of n-3 fatty acids and antioxidants in combination with effective ratios of insoluble and soluble fibers are ingredients combined with other ingredients to provide a nutritionally complete diet. be. In some embodiments, the food product is a nutritionally complete meal for a mature companion animal. In certain aspects, the food product is a nutritionally complete diet formulated for a mature companion dog.

In some embodiments, the composition comprises an effective amount of n-3 fatty acids and antioxidants along with proteins and/or fats and/or carbohydrates in combination with an effective ratio of insoluble and soluble fibers. It includes food compositions suitable for consumption by animals, particularly dogs. In some embodiments, the nutritionally complete and balanced dog food composition, in addition to, for example, n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber, comprises 4% to 90% by weight, 4% by weight -75% by weight, 5% to 75% by weight, 10% to 60% by weight protein, or 15% to 50% by weight protein based on total weight of dry matter based composition, dry matter based composition 0% to 90%, 2% to 80%, 5% to 75%, and 10% to 50% carbohydrate and dry matter based composition based on total weight of product It may contain from 2% to 60%, 5% to 50%, and 10% to 35% fat by weight. In some embodiments, for example, in addition to n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber, the nutritionally complete and balanced dog food composition contains 0-15% or 2% by weight It may further contain ˜8% by weight of other vitamins and minerals, antioxidants, and other nutrients such as, for example, amino acids that support the nutritional needs of animals.

The composition contains at least one n-3 fatty acid, also known as an omega-3 fatty acid. Omega-3 fatty acids, also called n-3 fatty acids, are a recognized group of polyunsaturated fatty acid carboxylic acids, also called polyunsaturated fatty acids (PUFAs). Omega-3 fatty acids are characterized by the presence of a double bond between carbon atoms t3 and 4, measured from the end of the molecule that does not contain a carboxyl group, i.e. three atoms away from the terminal methyl group in the chemical structure. It is a feature. They have long chain polyalkenyl groups, normal or branched, having from about 8 to about 24 carbon atoms, preferably from about 10 to about 22 carbon atoms, including the carbon atoms of the carboxyl group.

Examples of omega-3 fatty acids include, but are not limited to, alpha-linoleic acid (ALA), docosahexanoic acid (DHA), eicosapentaenoic acid (EPA), and octadecatetraenoic acid. In some embodiments, the composition comprises one of ALA, DHA, or EPA. In some embodiments, the composition comprises at least two of ALA, DHA, or EPA. In some embodiments, the composition comprises all three of ALA, DHA, or EPA. Omega-3 fatty acids are generally regarded as the most important and significant of the long-chain omega-3 fatty acids, typified by EPA and DHA. Generally, these long chain fatty acids are present only in relatively small amounts, almost trace amounts, or none at all in typical pet food compositions. The fatty acid composition of foods consumed by companion pets, such as dogs and cats, directly affects the biological levels of fatty acids found in their blood. Natural products with relatively high levels of omega-3 unsaturated fatty acids such as EPA and DHA are obtained from marine oils such as salmon, anchovies, sardines, and menhaden. These natural oils can be enriched with higher percentages of omega-3 fatty acids.

Derivatives of omega-3 fatty acids may also be used. Many types of derivatives are well known to those skilled in the art. Examples of suitable derivatives include esters such as branched or unbranched and/or saturated or unsaturated C-C cycloalkyl esters, especially C-C alkyl esters. Their systemic potential is recognized in the art and described, for example, in US Pat. Nos. 5,776,913 and 6,015,798. "Omega-3 fatty acid" as used in the specification and claims includes derivatives thereof.

With respect to the amount of omega-3 fatty acids or mixtures of omega-3 fatty acids, measured in the amount of the dietary composition per day, in some embodiments from 0.6 to 0.6 of the daily nutritional intake on a dry matter basis. 0.9% by weight, and in some embodiments, 0.65-0.85% by weight of daily nutrient intake on a dry matter basis, and in some embodiments, 1% on a dry matter basis. 0.70-0.80% by weight of the daily nutrient intake, and in some embodiments 0.72-0.79% by weight of the daily nutrient intake on a dry matter basis is administered. should. In some embodiments, EPA and DHA are preferred omega-3 fatty acids.

In some embodiments, the method comprises about 10-15% by weight of the daily nutrient intake on a dry matter basis, and in some embodiments 11-11% of the daily nutrient intake on a dry matter basis. 14% and in some embodiments 12-13% of the daily nutrient intake on a dry matter basis and in some embodiments 12.5% of the daily nutrient intake on a dry matter basis. administering total fatty acids in an amount equivalent to 1-12.6% by weight, and in some embodiments, 12.2-12.4% by weight of daily nutrient intake on a dry matter basis. . The ratio of n-3 fatty acids to total fatty acids is 4.0-8.5%, in some embodiments 4.5-8.0%, in some embodiments 5.0-7.5 %, in some embodiments 5.5-7.0%, in some embodiments 5.5-6.5%.

The composition also includes at least one antioxidant. Antioxidants are well known in the art. Examples of antioxidants include, but are not limited to, vitamin C, vitamin E (tocopherols and/or tocotrienols), glutathione, lipoic acid, melatonin, carnitine, and beta-carotene. In some embodiments, the composition comprises at least one of vitamin C, vitamin E (tocopherols and/or tocotrienols), glutathione, lipoic acid, melatonin, or beta-carotene. In some embodiments, the composition comprises at least two of vitamin C, vitamin E (tocopherols and/or tocotrienols), glutathione, lipoic acid, melatonin, or beta-carotene. In some embodiments, the composition comprises at least three of vitamin C, vitamin E (tocopherols and/or tocotrienols), glutathione, lipoic acid, melatonin, or beta-carotene. In some embodiments, the composition comprises at least four of vitamin C, vitamin E (tocopherols and/or tocotrienols), glutathione, lipoic acid, melatonin, or beta-carotene. In some embodiments, the composition comprises at least five or more of vitamin C, vitamin E (tocopherols and/or tocotrienols), glutathione, lipoic acid, melatonin, and/or beta-carotene. In some embodiments, the composition comprises vitamin C and vitamin E. Vitamin C may be administered to the diet as ascorbic acid and its various derivatives such as calcium phosphate, cholesteryl salts, 2-monophosphate, etc., which exert vitamin C-like activity after ingestion by the pet. They can be in any form, including, for example, liquid, semisolid, solid, and heat stable forms.

Vitamin C at a level of greater than 400 ppm of the daily nutrient intake, in some embodiments at a level of greater than 450 ppm of the daily nutrient intake, in some embodiments at a level of greater than the daily nutrient intake at a level of greater than 475 ppm of the daily nutrient intake, in some embodiments at a level of greater than 480 ppm of the daily nutrient intake, in some embodiments at a level of greater than 490 ppm of the daily nutrient intake, In embodiments, it may be provided at a level of greater than 500 ppm of daily nutrient intake, and in some embodiments at a level of greater than 550 ppm of daily nutrient intake. Vitamin E at a level of greater than 1000 IUK of the daily nutrient intake, in some embodiments at a level of greater than 1200 IUK of the daily nutrient intake, in some embodiments at a level of the daily nutrient intake in some embodiments at a level of greater than 1300 IUK of daily nutrient intake, and in some embodiments at a level of greater than 1500 IUK of daily nutrient intake obtain.

Dietary fiber refers to plant constituents that are resistant to digestion by animal digestive enzymes. The dietary fiber content of a composition can be determined by any number of methods known to those skilled in the art, such as those published by OMA. Dietary fibers include soluble and insoluble fibers.

Soluble fiber is resistant to digestion and absorption in the small intestine, but undergoes complete or partial fermentation in the large intestine. Examples of soluble fiber sources include beet pulp, guar gum, chicory root, psyllium, pectin, blueberries, cranberries, pumpkin, apples, oats, beans, citrus, barley, peas, and the like. Cellulose, whole wheat products, wheat oat, corn bran, flaxseed, grapes, celery, kidney beans, cauliflower, potato skins, fruit skins, vegetable skins, peanut hulls, and soybean fiber. Insoluble fiber may be supplied from a variety of sources. Crude fiber includes, for example, the indigestible components contained in the cell walls and cell contents of plants such as grains, such as the husks of grains such as rice, corn, and legumes. The crude fiber content of the composition can be determined by any number of methods known by those skilled in the art, preferably OMA Method 991.43/32.1.17 (1994).

The combination of insoluble fiber and soluble fiber has a ratio of insoluble fiber to soluble fiber (amount of insoluble fiber/amount of soluble fiber), in some embodiments a ratio in the range of 2.0 to 3.0, and , in some embodiments at a ratio ranging from 2.1 to 2.9, and in some embodiments at a ratio ranging from 2.2 to 2.8, and in some embodiments in a ratio ranging from 2.3 to 2.7, and in some embodiments a ratio ranging from 2.4 to 2.6, and in some embodiments from 2.4 to 4.0% or more of the daily nutrient intake on a dry matter basis, in some embodiments 4.5% or more of the daily nutrient intake on a dry matter basis, at a ratio in the range of 2.5; In some embodiments, 4.6% or more of the daily nutrient intake on a dry matter basis, in some embodiments, 4.7% or more of the daily nutrient intake on a dry matter basis, some 4.8% or more of the daily nutrient intake on a dry matter basis, in some embodiments, 4.9% or more of the daily nutrient intake on a dry matter basis, some implementations In form, it is provided in an amount equal to or greater than 5.0% of the daily nutritional intake on a dry matter basis.

In some embodiments, the composition used in the method comprises a daily nutrient intake on a dry matter basis in an amount of 0.6-1.4% or more of the daily nutrient intake on a dry matter basis. in an amount not less than 0.7-1.3% by weight on a dry matter basis of the daily nutritional intake in an amount not less than 0.8-1.2% by weight on a dry matter basis. Crude fiber in an amount of 0.9-1.1% or more of the daily nutritional intake on a dry matter basis in an amount of 0.9-1.1% or more.

Sources of proteins, carbohydrates, fats, vitamins, minerals, balance agents, etc. suitable for inclusion in the compositions, particularly in foods administered in the methods provided herein, are conventional materials known to those skilled in the art. can be selected from

Proteins useful as components of food compositions include animal-derived proteins such as animal proteins including mammalian, avian proteins, reptile, amphibian, fish, invertebrate proteins and combinations thereof; Deer, rabbit, horse, kangaroo, its milk, curds, whey or blood, and from organs such as smooth muscle, striated muscle, liver, kidney, intestine or heart; smooth muscle, striated muscle, liver internal tissues and organs such as, kidneys, intestines or heart, chicken meat, including chicken eggs; additional avian protein sources include turkey, goose, duck, ostrich, quail, pigeon, their eggs and smooth muscle striated muscle, liver, kidney amphibian sources include frogs or salamanders; reptile protein sources include alligators, lizards, turtles and snakes; fish protein sources include catfish, herring, salmon, tuna, bluefish, cod, halibut, trout, swordfish and their eggs; invertebrate protein sources include lobster, crab, clams, mussels or oysters and combinations thereof, meat protein isolates, whey protein Proteins such as isolates, egg proteins, mixtures thereof, etc., as well as soy protein isolates, corn gluten meal, wheat gluten, mixtures thereof, etc. may be included.

In some embodiments, carbohydrates useful as ingredients in food compositions include, but are not limited to, corn, whole yellow corn, cereal sorghum, wheat, barley, rice, millet, brewer's rice extract, oat grater. , and polysaccharides (eg, starches and dextrins), and one or more of sugars (eg, sucrose, lactose, maltose, glucose and fructose) that are metabolized for energy when hydrolyzed. Examples of additional carbohydrate sources suitable for inclusion in the compositions disclosed herein include fruits and vegetables.

Fats useful as components of food compositions can be derived from any source such as, but not limited to, poultry fat, beef tallow, lard, choice white grease, soybean oil, corn oil, canola oil, sunflower oil, mixtures thereof, and the like. There may be. The fat may be completely incorporated within the food composition, deposited on the outside of the food composition, or a mixture of the two methods.

In some embodiments, the composition comprises glucosamine, chondroitin, chondroitin sulfate, methylsulfonylmethane (MSM), creatine, antioxidants, pernacana liqueurata, omega-3 fatty acids, omega-6 fatty acids, and mixtures thereof. further comprising an effective amount of one or more substances selected from the group consisting of

In some embodiments, the food composition further comprises, but is not limited to, arginine, histidine, isoleucine, leucine, lysine, methionine (including DL-methionine and L-methionine), phenylalanine, threonine, tryptophan, valine, taurine , carnitine, alanine, aspartate, cystine, glutamate, glutamine, glycine, proline, serine, tyrosine, and hydroxyproline.

In some embodiments, the food composition further comprises, in addition to the omega-3 fatty acids described above, without limitation, lauric acid, myristic acid, palmitic acid, palmitoleic acid, margaric acid, margaloleic acid, stearic acid, oleic acid. acid, linoleic acid, gadoleic acid, arachidonic acid, behenic acid, erucic acid, docosatetraic acid, and the like.

In some embodiments, the food composition further comprises one or more macronutrients such as, but not limited to, moisture, protein, fat, crude fiber, ash, dietary fiber, soluble fiber, insoluble fiber, raffinose, and stachyose. including.

In some embodiments, the food composition further comprises one or more micronutrients such as, but not limited to, beta-carotene, alpha-lipoic acid, glucosamine, chondroitin sulfate, lycopene, lutein, and quercetin. .

In some embodiments, the food composition further contains calcium, phosphorus, potassium, sodium, chlorine, iron, copper, manganese, zinc, iodine, selenium, selenium, cobalt, sulfur, fluorine, chromium, boron, and oxalic acid. Contains one or more minerals such as, but not limited to, acid salts.

In some embodiments, the food composition further comprises stabilizing substances, such as substances that tend to extend the shelf life of the composition. Potentially suitable examples of such substances include, for example, preservatives, antioxidants, synergists and scavengers, packaging gases, stabilizers, emulsifiers, thickeners, gelling agents, and wetting agents. . Examples of emulsifiers and/or thickeners include, for example, gelatin, cellulose ethers, starches, starch esters, starch ethers, and modified starches.

In some embodiments, the food composition contains additives intended for coloring, palatability, and nutritional purposes such as colorants, iron oxide, sodium chloride, potassium citrate, potassium chloride, and Other edible salts, vitamins, minerals and flavors may be included. The amount of such additives in the composition is generally up to 5% (based on the dry weight of the composition).

Preparation of the composition

A composition comprising the n-3 fatty acids, antioxidants, insoluble fiber, and soluble fiber described above can be prepared as a food suitable for consumption by dogs. These foods may be of any consistency or moisture content, ie the compositions may be moist, semi-moist, or dry foods. A "moist" food is generally a food with a moisture content of 60% to 90% or more. "Dry" foods are foods that generally have a moisture content of 3% to 11% and are often manufactured in the form of small pieces or kibbles. "Semi-moist" foods generally have a moisture content of 25% to 35%. The food product may also contain one or more consistency ingredients, such as, for example, soft, chewy meat-like particles or pieces, and kibble with an outer grain component or coating and an inner "cream" component. good.

In some embodiments, the food product comprising n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber described above is prepared in canned or wet form using conventional food preparation processes known to those skilled in the art. can be The comminuted animal protein tissue is usually mixed with other ingredients such as grains, suitable carbohydrate sources, fats, oils, and formula ingredients, vitamin and mineral mixtures, inorganic salts, cellulose, beet pulp, etc., and processed. Contains sufficient water. These ingredients are mixed in a vessel suitable for applying heat during blending of the ingredients. Heating of the mixture can be accomplished using any suitable method, such as, for example, by direct steam injection or by using a vessel equipped with a heat exchanger. After addition of all ingredients of the formulation, the mixture is heated to a temperature of 50°F to 212°F. Temperatures outside this range can be used, but may not be commercially practical without other processing aids. Upon heating to a suitable temperature, the material is usually in viscous liquid form and dispensed into cans. Close the container with a lid. The sealed cans are then placed in conventional equipment designed to sterilize the contents. Sterilization can generally be accomplished by heating to temperatures in excess of about 230° C. for an appropriate period of time, depending on the temperature and composition used and related factors. The compositions and food products of the present invention may also be added to or combined with food compositions before, during, or after their preparation.

In some embodiments, food products may be prepared in dry form using conventional processes known to those skilled in the art. Generally, dry ingredients, including dry animal proteins, vegetable proteins, grains, etc., are ground and mixed together. Liquid or moist ingredients including fats, oils, water, animal proteins, water, etc. are added and mixed with the dry matter. The specific formulations, order of addition, combination, and methods and equipment used to combine the various ingredients can be selected from those known in the art. For example, in certain embodiments, the resulting mixture is such that the mixture of dry and wet ingredients is subjected to mechanical work at high pressure and temperature, passed through a small opening or opening, and into kibble, for example with a rotating knife. It is cut into kibbles or similar dry pieces that are formed using an extrusion process. The resulting kibble is dried and optionally coated with one or more topical coatings including, for example, flavors, fats, oils, powders, and the like. Kibble can also be made from the dough using a baking method rather than extrusion, in which the dough is placed in a mold followed by a dry heating process.

When preparing a composition, an optional ingredient can generally be incorporated into the composition during the processing of the formulation, e.g., during and/or after mixing the other ingredients of the composition. Distribution of these ingredients into the composition can be accomplished by conventional means. In certain embodiments, the comminuted animal and/or poultry proteinaceous tissue is mixed with other ingredients, including nutritional balancers, inorganic salts, and other ingredients, including cellulose, beet pulp, fillers, and the like. is mixed with sufficient water for processing.

In some embodiments, compositions are formulated to be more chewable. In certain embodiments, compositions and food products are formulated to address specific nutritional differences between animal species and breeds, and one or more of animal attributes. For example, dog foods are typically formulated based on, for example, life stage, age, size, weight, body composition, and breed.

In another embodiment, treats comprising effective amounts of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber are extruded or baked, as described above, e.g., similar to those described below for dry foods. Prepared by the process may provide an edible product. Treats include, for example, compositions given to an animal during non-meal times to attract food. The treat may be nutritious, the composition comprises one or more nutrients, and may have, for example, the compositions described above with respect to foods. Nutrient-free treats encompass any other treat that is non-toxic. The composition may be coated onto the treat, incorporated into the treat, or both.

In another embodiment, an animal toy is provided that is a chewable or consumable toy. Such toys are typically prepared by coating any existing toy with effective amounts of n-3 fatty acids, antioxidants, insoluble fiber, and soluble fiber, as outlined above. Thus toys include, for example, chew toys. Toys intended for dogs include, for example, artificial bones. In certain embodiments, the compositions of the present invention can form a coating on the surface of the toy or on the surfaces of parts of the toy, can be incorporated into parts of the toy or the entire toy, or both. can. A wide variety of suitable toys are currently on the market. See, for example, US Pat. No. 5,339,771 (and references disclosed in US Pat. No. 5,339,771). See also, for example, US Pat. No. 5,419,283 (and references disclosed in US Pat. No. 5,419,283). It should be appreciated that the present invention contemplates both partially consumable toys (e.g., toys containing plastic components) and fully consumable toys (e.g., rawhide and various artificial bones). . It should further be appreciated that the present invention contemplates toys for use by companion animals, particularly dogs or cats.

All publications mentioned herein are incorporated by reference for the purpose of describing and disclosing the materials and methodologies reported in the publications that may be used in connection with the present invention.

Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. The detailed description and specific examples, while indicating preferred embodiments of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention. should be understood.

Example 1

The microbial metabolite 4-ethylphenyl sulfate (4-EPS) is associated with stress and anxiety. 4-EPS levels in the blood can be measured. Blood is drawn to determine the plasma metabolic profile. 4-EPS levels in plasma can be measured by a commercial laboratory (Metabolon, Durham, NC, USA). Extracted supernatants are split and run on gas chromatography and liquid chromatography mass spectrometer platforms. The 4-EPS peak is known and the area under the peak for each sample can be normalized to the known sample (see Evans, AM, et al. (2009)). An integrated non-targeted ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of small molecule complements in biological systems. Anal. Chem. 81, 6656-6667. ) Gas chromatography (for hydrophobic molecules) and liquid chromatography (for hydrophilic molecules) are used to identify and provide relative quantitation of metabolites such as 4-EPS present in plasma samples. （また、例えば、Ｂａｌｌｅｔ，Ｃ．ら（２０１８）Ｎｅｗ ｅｎｚｙｍａｔｉｃ ａｎｄ ｍａｓｓ ｓｐｅｃｔｒｏｍｅｔｒｉｃ ｍｅｔｈｏｄｏｌｏｇｙ ｆｏｒ ｔｈｅ ｓｅｌｅｃｔｉｖｅ ｉｎｖｅｓｔｉｇａｔｉｏｎ ｏｆ ｇｕｔ ｍｉｃｒｏｂｉｏｔａ－ｄｅｒｉｖｅｄ ｍｅｔａｂｏｌｉｔｅｓ、Ｃｈｅｍ．Ｓｃｉ．，９、６２３３－６２３９；Ａｋｉｙａｍａ，Ｙら（２０１２）Ａ Ｍｅｔａｂｏｌｏｍｉｃ Ａｐｐｒｏａｃｈ ｔｏ Ｃｌａｒｉｆｙｉｎｇ ｔｈｅ Ｅｆｆｅｃｔ ｏｆ ＡＳＴ－１２０ ｏｎ ５／６ Ｎｅｐｈｒｅｃｔｏｍｉｚｅｄ Ｒａｔｓ ｂｙ Ｃａｐｉｌｌａｒｙ Ｅｌｅｃｔｒｏｐｈｏｒｅｓｉｓ ｗｉｔｈ Ｍａｓｓ Ｓｐｅｃｔｒｏｍｅｔｒｙ（ＣＥ－ＭＳ）Ｔｏｘｉｎｓ ４（１１）、１３０９－１３２２；およびＫｉｋｕｃｈｉ Ｋ，ら（２０１０） Ｍｅｔａｂｏｌｏｍｉｃ ｓｅａｒｃｈ ｆｏｒ ｕｒｅｍｉｃ ｔｏｘｉｎｓ ａｓ indicators of the effect of an oral sorbent AST-120 by liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 878:0297).

A study was completed in which 40 dogs were each fed three foods (pre-fed, control, test) at different times. As shown in Table 1, pre-feeding contained low soluble fiber, high insoluble fiber, low n-3 fatty acids and antioxidants, and control and test foods, respectively, high soluble fiber, low insoluble fiber, high Contains n-3 fatty acids and high antioxidants.

The insoluble to soluble fiber ratios of the pre-fed, control and test foods were 3.88%, 2.49% and 2.39%, respectively. The pre-fed total n-3 fatty acid percentage is 3.2. The percentage of total n-3 fatty acids in the control and test foods were 5.87 and 6.42, respectively.

All dogs were pre-fed for the first 30 days (Days 0-30). After the initial pre-feeding period, the control group (20 animals) received the control food for 30 days (Days 31-60) and the test group (20 animals) the test food for 30 days (Days 31-60). Animals then underwent a 30-day washout period (days 61-90), during which they were pre-fed. After a 30-day washout period of pre-feeding, a 30-day crossover (Days 91-120) was performed in which groups were fed previously unfed food (control or test). That is, after completion of the washout period, dogs fed the control food on days 31-60 received the test food on days 91-120, and dogs fed the test food on days 31-60 Control food was given on day ˜120.

Samples were collected at the end of each 30-day period to compare levels of 4-EPS in blood and changes in microbial composition in faeces. Dogs had the highest pre-fed 4-EPS levels compared to test or control diets (P<0.0001) (FIG. 1). There were specific microbial OTUs that were significantly different in abundance after pre-feeding compared to the test or control food (Table 2). (OUT means behavioral taxonomic unit. OTU is used to classify bacteria based on sequence similarity.) These include Odrybacter, Parabacteroid, Brautia, and Pseudomonadaceae. included non-taxonomic genera. All genera decreased after ingestion of the pre-fed, except for the Pseudomonadaceae genera, which rose after the dogs ingested the pre-fed (Table 2). The genera Odribacter, Parabacteroides, and Brautia showed a negative correlation with the blood 4-EPS level, and the unclassified genera of the Pseudomonadaceae showed a positive correlation with the blood 4-EPS level (Table 3). There were no significant differences in microbial composition and control food consumption after testing.

In summary, the combination of insoluble and soluble fiber, n-3 fatty acids, and antioxidants contained in the test and control foods (i.e., an insoluble to soluble fiber ratio of 2.4 to 2.5; vitamin C and Foods with levels of vitamin E above 400 ppm and above 1000 IUK, respectively; and percentages of total n-3 fatty acids between 5.5 and 6.5) reduce levels of the microbial stress-related metabolite, 4-EPS. This unique combination of fiber, antioxidants, and n-3 fatty acids reduces 4-EPS by altering the gut microbial composition.

A microbial signature in dogs associated with changes in 4-EPS is identified. Fiber-fermenting microorganisms such as Parabacteroids, Brautia, and Odribacter are negatively correlated with increased 4-EPS levels. Unclassified bacterial genera of the Pseudomonadaceae family were positively correlated with circulating levels of 4-EPS, which increased after ingestion of pre-feeding.

Foods containing high soluble fiber, n-3 fatty acids, and antioxidants reduce 4-EPS by increasing parabacteroids, Brautia, and Odrybacter and decreasing Pseudomonadaceae genera. Table 2 shows the difference in relative abundance of bacterial OTUs after ingestion of pre-fed, control, and test foods.

Example 2

The compositions below are based on total nutrition provided per day.

In some embodiments, the amount of n-3 fatty acids, based on the total weight of the composition on a dry matter basis, represents 0.6-0.9% of the daily nutritional intake, and the amount of vitamin C The amount corresponds to more than 400 ppm of the daily nutrient intake, the amount of vitamin E corresponds to more than 1000 IUK of the daily nutrient intake, the amount of insoluble and soluble fiber is 2.0-3. A ratio of 0 (insoluble/soluble) corresponds to about 4.0-6.0%. In some embodiments, the composition comprises chicken in an amount of 5%-25%, egg protein in an amount of 4%-15%, 6%-20%, based on the total weight of the composition on a dry matter basis. 0.5% to 2% of its vegetables, 0.5% to 2% of its fruit, and 5% to 50% of millet, brewed, based on the total weight of the composition on a dry matter basis. including carbohydrates selected from white rice, oat clots, and combinations thereof.

In some embodiments, the amount of n-3 fatty acids is, in some embodiments, 0.65-0.85% of the daily nutritional intake, based on the total weight of the composition on a dry matter basis. , in some embodiments 0.70-0.80% of the daily nutrient intake, in some embodiments 0.72-0.79% of the daily nutrient intake.

In some embodiments, based on the total weight of the composition on a dry matter basis, the amount of vitamin C is 450 ppm, in some embodiments 475 ppm, in some embodiments 480 ppm, in some embodiments 485 ppm, in some embodiments 490 ppm, in some embodiments 500 ppm, in some embodiments 550 ppm or more, and the amount of vitamin C is 1000 IUK, in some embodiments 1200 IUK, in some embodiments in some embodiments 1300 IUK, in some embodiments 1400 IUK, in some embodiments 1500 IUK or more.

In some embodiments, the amount of insoluble fiber and soluble fiber, based on the total weight of the composition on a dry matter basis, is 4.0%, in some embodiments 4.1%, in some embodiments 4.2%, in some embodiments 4.3%, in some embodiments 4.4%, in some embodiments 4.5%, in some embodiments 4.6 %, in some embodiments 4.7%, in some embodiments 4.8%, in some embodiments 4.9%, in some embodiments 5/0% or greater , the ratio of insoluble fiber to soluble fiber (i.e. amount of insoluble fiber/amount of soluble fiber) is 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2 .7, 2.8, 2.9, 3.0, and in some embodiments in the range of 2.4 to 2.6 and in some embodiments in the range of 2.4 to 2.5 is.

In certain embodiments, the composition comprises, based on the total weight of the composition on a dry matter basis, 5%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, It may contain chicken in an amount of 22.5%, or 25%. In certain embodiments, the composition comprises, based on the total weight of the composition on a dry matter basis, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, It may contain egg protein in amounts of 13%, 14%, or 15%. In certain embodiments, the composition comprises, based on the total weight of the composition on a dry matter basis, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, May contain corn gluten meal in amounts of 15%, 16%, 17%, 18%, 19%, or 20%. In certain embodiments, the composition comprises 0.0%, 0.5%, 0.6%, 0.7%, 0.8%, 0.8%, 0.0%, 0.5%, 0.6%, 0.7%, 0.8%, 0.8%, based on the total weight of the composition on a dry matter basis. 9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1 Additional plant sources may be included in amounts of .9%, or 2.0%. In certain embodiments, the composition comprises 0.0%, 0.5%, 0.6%, 0.7%, 0.8%, 0.8%, 0.0%, 0.5%, 0.6%, 0.7%, 0.8%, 0.8%, based on the total weight of the composition on a dry matter basis. 9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1 Additional fruit sources may be included in amounts of .9%, or 2.0%. In certain embodiments, the composition comprises, based on the total weight of the composition on a dry matter basis, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or in an amount of 50%, carbohydrates selected from millet, sake rice, oat flour, and combinations thereof. In certain aspects of these embodiments, a composition of the invention may comprise a dry weight of carbohydrate source within a range defined as an endpoint by any two of these values.

Example 3

Table 3 describes certain embodiments with composition percentages (% of dry matter weight of component composition).

A daily diet containing effective amounts of n-3 fatty acids, vitamin C, vitamin E, insoluble fiber, and soluble fiber is believed to be beneficial for dogs identified as having stress. In some embodiments, the method identifies a dog that has or is suspected of having stress, a stress disorder, or is suspected of exhibiting symptoms of stress or a stress disorder, administering an effective amount of n-3 fatty acids, vitamins, including feeding it a daily diet containing C, vitamin E, insoluble fiber and soluble fiber.

Example 4

Table 4 lists the ingredients used in certain embodiments with the proportions of the composition (% of dry matter weight of the ingredient composition).

Example 5

Table 5 lists the ingredients used in certain embodiments with the proportions of the composition (% of dry matter weight of the ingredient composition).

Example 6

Table 6 lists the ingredients used in certain embodiments with the proportions of the composition (% of dry matter weight of the ingredient composition).

Example 7

Table 7 lists the ingredients used in certain embodiments with the proportions of the composition (% of dry matter weight of the ingredient composition).

Example 8

Table 8 lists the ingredients used in certain embodiments with the proportions of the composition (% of dry matter weight of the ingredient composition).

Example 9

Table 9 lists the ingredients used in certain embodiments with the proportions of the composition (% of dry matter weight of the ingredient composition).

Example 10

* 特記がない限り Table 10 lists the ingredients used in certain embodiments with composition proportions (% of dry matter weight of ingredient composition).

* Unless otherwise noted

Claims (29)

A method for treating anxiety or stress in an animal comprising administering to said animal an effective amount of n-3 fatty acids, antioxidants, insoluble fiber and soluble fiber in an effective ratio of insoluble fiber to soluble fiber. method, including The animal has n-3 fatty acids representing 0.6-0.9% of the daily nutrient intake, vitamin C at a level of 400 ppm or more of the daily nutrient intake, and 1000 IUK of the nutrient intake per day. 2. The method of claim 1, wherein levels of vitamin E, and insoluble fiber and soluble fiber are administered at an insoluble fiber/soluble fiber ratio of 2.0 to 3.0. 2. The method of claim 1, wherein the animal is administered n-3 fatty acids corresponding to 0.65-0.85% of its daily nutritional intake. 2. The method of claim 1, wherein the animal is administered n-3 fatty acids corresponding to 0.70-0.75% of its daily nutritional intake. 2. The method of claim 1, wherein the animal is administered n-3 fatty acids corresponding to 0.72-0.79% of its daily nutritional intake. A method according to any one of claims 1 to 5, wherein the animal is administered vitamin C corresponding to 450ppm of daily nutritional intake. The method of any of claims 1-5, wherein the animal is administered vitamin C corresponding to 475ppm of daily nutritional intake. The method of any of claims 1-5, wherein the animal is administered vitamin C corresponding to 490ppm of daily nutritional intake. The method of any of claims 1-8, wherein the animal is administered vitamin E corresponding to a daily nutritional intake of 1100 IUK. The method of any of claims 1-8, wherein the animal is administered vitamin E corresponding to a daily nutritional intake of 1200 IUK. The method of any of claims 1-8, wherein the animal is administered vitamin E corresponding to a daily nutritional intake of 1400 IUK. 12. The method of any of claims 1-11, wherein the animal is administered insoluble and soluble fiber at an insoluble/soluble fiber ratio of 2.2-2.7. A method according to any preceding claim, wherein the animal is administered insoluble and soluble fiber at an insoluble/soluble fiber ratio of 2.3 to 2.6. 12. The method of any of claims 1-11, wherein the animal is administered insoluble and soluble fiber at an insoluble/soluble fiber ratio of 2.4-2.5. 15. The method of any of claims 1-14, wherein the animal is administered insoluble and soluble fiber in an amount corresponding to 4.0-5.5% of its daily nutritional intake. 15. The method of any of claims 1-14, wherein the animal is administered insoluble and soluble fiber in an amount corresponding to 4.5-5.0% of its daily nutritional intake. 15. The method of any of claims 1-14, wherein the animal is administered insoluble and soluble fiber in an amount corresponding to 4.7-4.9% of its daily nutritional intake. 18. The method of any of claims 1-17, wherein said animal is a dog. 19. The method of claim 18, wherein the dog is identified as having elevated 4-ethylphenyl sulfate levels. 19. The method of claim 18, wherein the dog has been previously identified as having canine anxiety. 19. The method of claim 18, wherein the dog has been previously identified as having canine stress symptoms. A food composition comprising an effective amount of n-3 fatty acids, vitamin C, vitamin E, insoluble fiber and soluble fiber for treating anxiety, stress or stress disorder in an animal, wherein said effective amount of n-3 Fatty acids represent 0.6-0.9% of the daily nutrient intake, vitamin C is at a level of 400 ppm or more of the daily nutrient intake, and vitamin E is the daily nutrient intake. of 1000 IUK and a ratio of insoluble fiber to soluble fiber insoluble fiber/soluble fiber of 2.0 to 3.0. said effective amount of n-3 fatty acids representing 0.65-0.85% of the daily nutrient intake, vitamin C at a level of 450 ppm or more of the daily nutrient intake, and vitamin E , a level of nutrient intake of 1100 IUK per day, and an insoluble/soluble fiber ratio of insoluble fiber and soluble fiber of 2.2 to 2.8. said effective amount of n-3 fatty acids representing 0.70-0.80% of the daily nutrient intake, vitamin C at a level of 475 ppm or more of the daily nutrient intake, and vitamin E , a level of nutrient intake of 1200 IUK per day, and an insoluble fiber/soluble fiber ratio of insoluble fiber and soluble fiber of 2.3 to 2.7. said effective amount of n-3 fatty acids representing 0.72-0.79% of the daily nutrient intake, vitamin C at a level of 490 ppm or more of the daily nutrient intake, and vitamin E , a level of nutrient intake of 1400 IUK per day, and an insoluble/soluble fiber ratio of insoluble fiber and soluble fiber of 2.4 to 2.5. A food composition according to any of claims 22-25, wherein the amount of insoluble and soluble fiber corresponds to 4.0-5.5% of the daily nutritional intake. A food composition according to any of claims 22-25, wherein the amount of insoluble and soluble fiber corresponds to 4.5-5.0% of the daily nutritional intake. A food composition according to any of claims 22-25, wherein the amount of insoluble and soluble fiber corresponds to 4.7-4.9% of the daily nutritional intake. The food composition according to any one of claims 22 to 28, wherein said food composition is a dog food composition.

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