JP2023507338A - Compositions and methods for treating and reducing the risk of conditions associated with elevated 4-ethylphenyl sulfate - Google Patents

Abstract

for treating anxiety or stress in animals, for reducing elevated 4-EPS levels in animals with elevated 4-EPS levels, for preventing elevated 4-EPS levels in animals, and beneficial in the microbiota of animals Compositions and methods are disclosed for promoting the growth of harmful microorganisms and inhibiting the growth of non-beneficial microorganisms. The method includes administering an effective amount of soy protein and vitamin C to the animal. A composition is disclosed comprising effective amounts of soy protein and vitamin C for use in the method. [Selection figure] None

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 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. Dogs experiencing stress can develop feelings of fear, excitement, 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, particularly 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 an effective amount of soy protein and vitamin C to the animal.
Methods of reducing elevated 4-EPS levels in an animal with elevated 4-EPS levels are provided. The method includes administering an effective amount of soy protein and vitamin C to the animal.
Methods are provided for preventing elevated 4-EPS levels in animals. The method comprises administering an effective amount of soy protein and vitamin C to an animal at risk of elevated 4-EPS levels.
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 an effective amount of soy protein and vitamin C to the animal.
Compositions are provided for treating anxiety or stress in animals. The composition comprises effective amounts of soy protein and vitamin C.
Compositions are provided for reducing elevated 4-EPS levels in an animal with elevated 4-EPS levels. The composition comprises effective amounts of soy protein and vitamin C.
Compositions are provided for preventing elevated 4-EPS levels in an animal. The composition comprises effective amounts of soy protein and vitamin C.
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 effective amounts of soy protein and vitamin C.

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, the present invention is directed to formulations and methods of treatment for dogs.

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 cats that are companion animals known as domestic or house cats or Felis domesticus. The term "cat" is synonymous with the term "feline."

Methods are provided for treating anxiety and stress in animals, particularly companion animals such as dogs or cats. The method includes administering an effective amount of a combination of both soy protein and vitamin C to the animal. The composition comprises effective amounts of soy protein and vitamin C. An effective amount of soy protein is 3.7-6.9% of the daily nutrient intake, in some embodiments 4.8-5.8% of the daily nutrient intake, in some implementations In form it is 5.3% of the daily nutritional intake. An effective amount of vitamin C is between 104.8 and 148.2 ppm of daily nutrient intake, in some embodiments between 119.1 and 137.9 ppm of daily nutrient intake, in some embodiments , 126.5 ppm of daily nutrient intake.

"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 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 the 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 percent of dry matter. Since foods, whether moist, moist or dry, generally contain a certain amount of water, the water component of such foods is excluded when calculating daily dry matter intake. be. 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, soy protein and vitamin C may be administered as supplements, treats, toys, or otherwise not incorporated into food provided to animals for their daily nutritional intake. .

In some preferred embodiments, the animal is a dog and the method comprises administering an effective amount of soy protein and vitamin C to the dog daily. The effective amount of soy protein administered to a dog per day is 3.7-6.9% of the daily nutritional intake, in some embodiments 4.8-5% of the daily nutritional intake. .8%, in some embodiments 5.3% of the daily nutritional intake. The effective amount of vitamin C administered to a dog per day is between 104.8 and 148.2 ppm of daily nutritional intake, in some embodiments between 119.1 and 137.5 ppm of daily nutritional intake. 9 ppm vitamin C, in some embodiments, 126.5 ppm vitamin C of daily nutritional intake. Preferably, the composition is a dog food composition comprising an effective daily amount of soy protein and vitamin C.

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.

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, anxiety disorders, and symptoms of anxiety 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," "effective amounts," and like terms refer to a specific biological result, i.e., 4- Refers to the amount of soy protein and vitamin C effective to achieve elevated EPS levels, treatment of anxiety, stress, and levels of beneficial and harmful microbes in the microbiome. In certain embodiments, an effective amount of the composition is administered for a period of time sufficient to affect treatment. In certain embodiments, the method comprises administering and consuming a composition comprising vitamin C and soy protein for a period of time sufficient to provide effective treatment and maintenance. The effective amount depends on the dog's ideal weight, age, sex, activity level, metabolizable energy of the composition, and frequency of feeding the composition, e.g., once, twice, or three times a day, and It may be based on several factors, including other compositions fed to the dog. In some embodiments, effective amount refers to the amount of soy protein and vitamin C administered based on total nutrient intake, wherein the amount of soy protein is 3.7-6% of total nutrient intake per day. 9%, the amount of vitamin C equates to 104.8-148.2 ppm of total nutrient intake per day. In some embodiments, the effective amount is a pet food comprising 3.7-6.9% soy protein and 104.8-148.2 ppm vitamin C on a dry matter basis of total daily nutritional intake point to Thus, a suitable amount of food to meet all daily nutritional and energy requirements for a canine subject is, on a dry matter basis, 3.7-6.9% soy protein and 104.8-148.2 ppm soy protein. Contains vitamin C.

In some embodiments, effective amount refers to the amount of soy protein and vitamin C administered based on total nutrient intake, wherein the amount of soy protein is 4.8-5% of total nutrient intake per day. Equal to .8%, the amount of vitamin C equates to 119.1-137.9 ppm of total nutrient intake per day. In some embodiments, the effective amount is a pet food comprising 4.8-5.8% soy protein and 119.1-137.9 ppm vitamin C on a dry matter basis of total daily nutritional intake point to Thus, a suitable amount of food to meet all daily nutritional and energy requirements for a canine subject is, on a dry matter basis, 4.8-5.8% soy protein and 119.1-137.9 ppm soy protein. Contains vitamin C.

In some embodiments, effective amount refers to the amount of soy protein and vitamin C administered based on total nutrient intake, wherein the amount of soy protein is less than 5.3% of total nutrient intake per day. Equally, the amount of vitamin C equals 126.5 ppm of total nutrient intake per day. In some embodiments, an effective amount refers to a pet food comprising 5.3% soy protein and 126.5 ppm vitamin C on a dry matter basis of total daily nutritional intake. Thus, a suitable amount of food to meet all daily nutritional and energy requirements for a canine subject contains 5.3% soy protein and 126.5 ppm vitamin C on a dry matter basis.

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 of 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% moisture content or moisture by weight. Food kibble can range in texture from hard to soft. Food kibble can range in internal structure from puffy to dense. Food kibble may be formed by an extrusion process or a baking process. In non-limiting examples, food kibble can have a uniform internal structure or a varying internal structure. For example, 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, 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 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).

When feeding a dog a diet containing effective amounts of vitamin C and soy protein, it is contemplated that a preferred method comprises feeding the dog a food product containing vitamin C and soy protein. In other embodiments, feeding the dog a diet containing effective amounts of vitamin C and soy protein is accomplished by administering the vitamin C and soy protein to the dog as a supplement or treat. Providing vitamin C and soy protein to dogs by any means, whether delivered in a pet food composition or as a separate supplement or treat, contains an effective amount of vitamin C and soy protein. Considered feeding the dog.

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

Diets may contain effective amounts of vitamin C and soy protein to reduce elevated levels of 4-EPS in dogs. A diet containing vitamin C and soy protein is useful for treating anxiety in dogs. A diet containing vitamin C and soy protein is useful for treating stress in dogs. A diet containing vitamin C and soy protein is useful in promoting beneficial microbial growth and inhibiting harmful microbial growth in the canine subject's microbiome, particularly in the gastrointestinal track.

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 disorders, an increased risk of developing anxiety stress, and an increase in the canine microbiota, especially in the gut microbiota. Effective amounts of soy protein and vitamin C have been identified that provide significant benefits to dogs identified as being at high risk of inhibiting the growth of beneficial microorganisms and promoting the growth of harmful microorganisms. In some embodiments, effective amounts of soy protein and vitamin C are combined with other ingredients to provide a nutritionally complete meal. In some embodiments, the food product is a nutritionally complete meal for adult dogs. In certain aspects, the food product is a nutritionally complete diet formulated for an adult companion dog.

In some embodiments, the composition comprises a food composition suitable for consumption by a companion animal, particularly a dog, in combination with an effective amount of vitamin C and soy protein, along with protein and/or fat and/or carbohydrate. include. In some embodiments, for example, in addition to vitamin C and soy protein, the nutritionally complete and balanced dog food composition contains 4% to 90%, 4% to 75%, 5% to 75% by weight, 10% to 60% protein by weight, or 15% to 50% protein by weight based on the total weight of the composition on a dry matter basis, 0% by weight based on the total weight of the composition on a dry matter basis -90%, 2% to 80%, 5% to 75%, and 10% to 50% carbohydrates, and 2% to 60% by weight based on the total weight of the composition on a dry matter basis. %, 5%-50%, and 10%-35% fat. In some embodiments, for example, in addition to vitamin C and soy protein, the nutritionally complete and balanced dog food composition contains 0-15% by weight or 2%-8% by weight of other vitamins, and may further contain minerals, antioxidants, and other nutrients such as, for example, amino acids that support the nutritional needs of animals. 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 liquid, semisolid, solid, and heat stable forms.

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

In addition to effective amounts of soy protein, in some embodiments, proteins useful as components of food compositions include animal proteins, including mammalian proteins, avian proteins, reptile, amphibian, fish, invertebrate proteins, and combinations thereof. Proteins of animal origin, such as animal proteins including; e.g. from cow, sheep, pig, goat, deer, rabbit, horse, kangaroo, its milk, curds, whey or blood, as well as smooth muscle, striated muscle, liver, from organs such as kidney, intestine or heart; internal tissues and organs such as smooth muscle, striated muscle, liver, kidney, intestine or heart, chicken, including chicken eggs; additional avian protein sources include turkey, goose, ducks, ostriches, quails, pigeons, their eggs and organs such as smooth muscle striated muscle, liver, kidney, intestine or heart; amphibian sources include frogs or salamanders; crocodiles, 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, Proteins such as crab, clam, mussels or oysters and combinations thereof, meat protein isolate, whey protein isolate, egg protein, mixtures thereof, etc., and soy protein isolate, corn gluten meal, wheat gluten, mixtures thereof, etc. can include

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

Fats useful as components of food compositions include, but are not limited to, any of poultry fat, beef tallow, lard, choice white grease, soybean oil, corn oil, canola oil, sunflower oil, mixtures thereof, and the like. may be derived from a source of 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 consists of glucosamine, chondroitin, chondroitin sulfate, methylsulfonylmethane (MSM), creatine, antioxidants, pernacanaliculata, omega-3 fatty acids, omega-6 fatty acids, and mixtures thereof It further comprises an effective amount of one or more substances selected from the group.

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, but is not limited to, lauric acid, myristic acid, palmitic acid, palmitoleic acid, margaric acid, margaroleic acid, stearic acid, oleic acid, linoleic acid, g-linolenic acid. , a-linolenic acid, stearidonic acid, arachidic acid, gadoleic acid, DHGLA, arachidonic acid, eicosateric acid, EPA, behenic acid, erucic acid, docosatetraic acid, and DPA. including.

In some embodiments, the food composition further comprises major amounts of one or more of, but not limited to, moisture, protein, fat, crude fiber, ash, dietary fiber, soluble fiber, insoluble fiber, raffinose, and stachyose. Contains nutrients.

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. include.

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

In some embodiments, the food composition, in addition to an effective amount of vitamin C, further contains vitamin A, vitamin D, vitamin E, quinoa grain, thiamine, riboflavin, niacin, pyridoxine, pantothenic acid, folic acid, vitamin B12, Biotin and one or more other vitamins such as, but not limited to, choline.

In some embodiments, the food composition further comprises fiber, which can be supplied from a variety of sources including, for example, cellulose, beet pulp, peanut shells, and soy fiber.

In some embodiments, the food composition further comprises stabilizing substances, eg, 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, packing 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 coloring agents, 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 dry matter of the composition).

Preparation of the composition

A composition comprising vitamin C and soy protein may be formulated 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%. Food products also include ingredients having one or more consistencies, such as, for example, particles or pieces such as soft, chewy meat, and kibble with an outer grain component or coating and an inner "cream" component. It's okay.

In some embodiments, food products comprising vitamin C and soy protein may be prepared in canned or wet form using conventional food preparation processes known to those skilled in the art. 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, a treat comprising an effective amount of soy protein and vitamin C can be prepared, for example, by an extrusion or baking process similar to that described below for dry foods to provide an edible product. can. Treats include, for example, compositions given to an animal during non-meal times to attract food. The treat may be nutritious, the composition may include one or more nutrients, and may have, for example, the compositions described above with respect to food. Nutrient-free treats encompass any other treat that is non-toxic. The composition may be coated with a therapeutic agent, incorporated with a therapeutic agent, or both.

In another embodiment, animal toys are provided that are chewable or consumable toys. Such toys are typically prepared by coating any existing toy with an effective amount of soy protein and vitamin C. Toys thus include, for example, chewable 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 a toy or on a component of a toy, can be incorporated into a part of a toy or an entire toy, or both. can. There is a wide range of suitable toys currently on the market. See, eg, 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. Reducing levels of 4-EPS has been shown to alleviate these symptoms.

A study was conducted using 30 adult dogs (ages 4-10) that demonstrated an optimal combination of vitamin C and soy protein, and 4-ethylphenyl sulfate (4-EPS), a stress-related microbial metabolite. decreased circulation levels.

Various levels of soy protein (0-24 grams) were combined with various levels of vitamin C (10.24-44.37 mg). This allows each dog to have different intakes of vitamin C and soy protein,

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 also, e.g., Evans, A. M., et al. (2009). Integrated Non-Targeted Ultra-Performance Liquid Chromatography/Method for Identification and Relative Quantification of Small Molecule Complements in Biological Systems. Electrospray ionization tandem mass spectrometry platform.Anal.Chem.81, 6656-6667.) Gas chromatography (for hydrophobic molecules) and liquid chromatography (for hydrophilic molecules) were used to detect the presence of 4 in plasma samples. - Identify and provide relative quantification of metabolites such as EPS. （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 7-8:29).

Circulating 4-EPS levels were determined and the correlation between soy protein and vitamin C intake and levels of 4-EPS in the blood was assessed.

Dogs prone to high 4-EPS may benefit from consumption of foods containing specific levels of vitamin C and soy protein. A matched pairs analysis comparing levels of 4-EPS in each dog after ingestion of food showed a significant decrease in 4-EPS with the addition of vitamin C and soy protein (P=0.04).

Daily intakes of vitamin C and soy protein that lead to low levels of 4-EPS are shown in Table 1. Various combinations of soy protein and vitamin C were evaluated for their potential to reduce levels of circulating 4-EPS in adult dogs. Increasing intake of vitamin C and soy protein increased circulating levels of 4-EPS, which then surprisingly decreased as intake increased. The lowest levels of 4-EPS were detected after daily intake of 10 grams of soy protein with 23.9 mg of vitamin C (Table 1). The average intake for adult dogs was 188.9 grams. Therefore, on a dry matter basis, consumption of food containing approximately 5.3% soy protein combined with 126.5 ppm vitamin C would result in the lowest levels of 4-EPS. The highest level of 4-EPS of 1.22468 was detected after ingesting 24 grams of soy protein with 44.4 mg of vitamin C. Pets above average after ingestion of low soy protein (0-3 grams) with 10.2-14.3 mg of vitamin C or high soy protein (18-24 grams) with 34.8-44.4 mg of vitamin C 4-EPS levels were indicated. Low levels of 4-EPS were achieved with a daily intake of 7-13 g (3.7-6.9%) soy protein and 19.8-28 mg (104.8-148.2 ppm) vitamin C. rice field. When consuming 9-11 grams (4.8-5.8%) soy protein with 22.5-25.3 mg (119.1-137.9 ppm) vitamin C per day, the level of 4-EPS was was low. Levels of 4-EPS were lowest when consuming 10 grams (5.3%) soy protein and 23.9 mg (126.5 ppm) vitamin C per day.

When provided in effective amounts, soy protein and vitamin C reduce circulating levels of 4-EPS. An anti-stress food for pets can be formulated by including effective amounts of soy protein and vitamin C, thereby lowering blood levels of the microbial toxin 4-EPS. An increase in this is associated with stress, anxiety, and brain damage. Such pet foods thereby address stress-related problems associated with elevated circulating levels of 4-EPS in pets.

Example 2

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

In some embodiments, the amount of soy protein is equal to 3.7-6.9% and the amount of vitamin C is 104.8-148.2 ppm, based on the total weight of the composition on a dry matter basis. be equivalent to. 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 soy protein is equal to 4.8-5.8% and the amount of vitamin C is 119.1-137.9 ppm based on the total weight of the composition on a dry matter basis. be equivalent to. In some embodiments, the amount of soy protein is equal to 5.3% and the amount of vitamin C is equal to 126.5 ppm, based on the total weight of the composition on a dry matter basis.

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 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 0.7%, 0.8%, 0.9%, based on the total weight of the composition on a dry matter basis. 0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1.9%, or Additional botanical sources may be included in amounts of 2.0%. In certain embodiments, the composition comprises 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 0.7%, 0.8%, 0.9%, based on the total weight of the composition on a dry matter basis. 0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1.9%, or Additional fruit sources may be included in amounts of 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, oatmeal, 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 2 describes certain embodiments with composition proportions (% of dry matter weight of component composition).

A daily diet containing vitamin C and soy protein may provide benefits to dogs identified as having stress. In some embodiments, the method identifies dogs that have or are suspected of having stress, a stress disorder, or are suspected of exhibiting symptoms of stress or a stress disorder and administer a daily diet containing vitamin C and soy protein. Including feeding it.

Example 4

Table 3 lists the ingredients used in certain embodiments with the proportions of the composition (% of dry matter weight of the ingredient composition).

Example 5

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

Example 6

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

Example 7

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

Example 8

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

Example 9

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

Example 10

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

Claims (13)

A method for treating anxiety or stress in an animal comprising administering an effective amount of soy protein and vitamin C to said animal. wherein the animal is administered soy protein equal to 3.7-6.9% of the daily nutritional intake and vitamin C at a level of 104.8-148.2 ppm of the daily nutritional intake. Item 1. The method according to item 1. The animal is administered a food composition comprising soy protein and vitamin C, the soy protein equaling 3.7-6.9% of the daily nutritional intake, and the vitamin C equaling the daily nutritional intake of 2. The method of claim 1, wherein the amount is at a level of 104.8-148.2 ppm. The animal is administered a food composition comprising soy protein and vitamin C, wherein the soy protein equals 4.8-5.8% of the daily nutritional intake and vitamin C equals 4.8-5.8% of the daily nutritional intake. The method of claim 1, wherein the amount is at a level of 119.1-137.9 ppm. The animals were administered a food composition comprising soy protein and vitamin C, wherein the soy protein equaled 5.3% of the daily nutritional intake and vitamin C equaled 126.5% of the daily nutritional intake. 2. The method of claim 1, at a level of 5 ppm. A method according to any one of claims 1 to 5, wherein said animal is a dog. 7. The method of claim 6, wherein the dog is identified as having elevated 4-ethylphenyl sulfate levels. 7. The method of claim 6, wherein the dog has been previously identified as having canine anxiety. 7. The method of claim 6, wherein the dog has been previously identified as having canine stress symptoms. 1. A food composition comprising an effective amount of soy protein and an effective amount of vitamin C for treating anxiety, stress, or a stress disorder in an animal, wherein said effective amount of soy protein, as a weight percent of dry matter, comprises3. 7-6.9% and said effective amount of vitamin C is 104.8-148.2 ppm. 11. The food composition of claim 10, wherein said effective amount of soy protein is between 4.8 and 5.8% and said effective amount of vitamin C is between 119.1 and 137.9 ppm as weight percent of dry matter. thing. 11. The food composition of claim 10, wherein said effective amount of soy protein is 5.3% and said effective amount of vitamin C is 126.5 ppm as weight percent of dry matter. A food composition according to any of claims 10-12, wherein said food composition is a canine food composition.