CN114828646A

CN114828646A - Compositions and methods for treating and reducing the risk of conditions associated with elevated 4-ethylphenyl sulfate

Info

Publication number: CN114828646A
Application number: CN201980102996.8A
Authority: CN
Inventors: 伊登·伊弗雷姆; 丹尼斯·朱厄尔
Original assignee: Hills Pet Nutrition Inc
Current assignee: Hills Pet Nutrition Inc
Priority date: 2019-12-19
Filing date: 2019-12-19
Publication date: 2022-07-29
Also published as: AU2019479118A1; JP2023507338A; WO2021126219A1; EP4021198A1; AU2019479118B2; JP7542065B2; CA3164483A1

Abstract

Compositions and methods for treating anxiety or stress in an animal, for reducing elevated 4-EPS levels in an animal having elevated 4-EPS levels, for preventing elevated 4-EPS levels in an animal, and for promoting the growth of beneficial microorganisms and inhibiting the growth of non-beneficial microorganisms in the microbiome of an animal are disclosed. The method comprises administering to the animal an effective amount of soy protein and vitamin C. Compositions comprising amounts of soy protein and vitamin C effective for use in the methods are disclosed.

Description

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

Background

Microbial toxin 4-ethylphenyl sulfate (4-EPS) is a metabolite produced by intestinal bacteria. Among other microbial metabolites, 4-EPS enters the systemic circulation. Increased levels of 4-EPS in the blood are associated with stress, anxiety, brain injury and other behavioral problems. It has been shown that a reduction in the level of 4-EPS reduces the symptoms of stress and anxiety.

Canine anxiety (anxiety) is the response to fear and anxious or apprehensive anxiety when dogs anticipate threatening or fear situations. Some individual dogs experience disproportionate levels of anxiety. Anxiety may progress to anxiety and may lead to behavioral and other problems. Some dogs experience generalized anxiety disorder in which fear responses are manifested in various situations in which a "normal" pet is unlikely to respond to it. Anxiety may manifest as one of a variety of anxiety disorders, such as generalized anxiety disorder, hyperstimulative anxiety disorder, separation anxiety disorder, confinement, noise phobia, and the like.

The causative factors may include genetic components, prenatal and neonatal stressors, maternal-fetal segregation, lack of socialization, strange biochemistry, or unpleasant results during previous exposure to stimuli (or similar stimuli). The most common causes are fear, segregation and aging. Fear-related anxiety may be caused by noisy noise, strange people or animals, visual stimuli, new or strange environments, specific situations, and the like. Age-related anxiety affects older dogs and may be associated with Cognitive Dysfunction Syndrome (CDS). Separation anxiety is a specific anxiety that results from the inability of pets to find comfort when separated from family members. About 14% of dogs suffer from separation anxiety. Some separation anxiety may be the result of abnormal attachment due to age and maturity of the puppy. In some cases, separation anxiety may occur in situations involving changes in family or daily living, while in other cases separation anxiety is associated with potential anxiety states along with other behavioral problems such as phobias.

Anxiety can lead to disruptive behavior (particularly when going out or towards the owner's possessions), painful vocalization, house-soiling (house-wetting), salivation, pacing, restlessness, lack of stability, anorexia, and repetitive or compulsive behavior. In some cases, anxiety may play a role in aggressive behavior.

Common symptoms of dog anxiety include assault, defecation in the house, running water, surge, disruptive behavior, depression, excessive barking, pacing, sitting restlessness, and repetitive or mandatory behavior. Different dogs, when suffering from anxiety, will exhibit different symptoms and combinations of symptoms.

Canine stress is the reaction of dogs to require changes or adaptations, usually manifested as a sensation of stress or stress. Dogs experiencing stress may experience feelings of fear, anxiety, hyperactivity, nervousness, oversensitivity or irritability. Negative stress, excessive stress and chronic stress can have detrimental effects on behavior, health and overall health. Stress has the potential to cause disease, suppress the immune system, cause undesirable behavior and increase arousal, which increases the likelihood of aggressive behavior.

Causes of stress in dogs include sadness, experiencing conflict, excessive or insufficient stimulation, overcrowded conditions, environmental changes (schedule, people, animals, increased noise); punitive training, insufficient social time, terrible events, ignorance, frustration, uncertainty, and the like.

Dogs communicate in different ways that they are experiencing stress. Some of the signs that dogs are experiencing stress include dilated pupils, tight around the eyes, whale's eyes/lunula eyes, yawning, licking the lips/nose, a surge of asthma, excessive salivation, smiling, shakiness of the teeth, bulging of the cheeks, exposure of the teeth, ruffled nose, arching of the back, or sticking up of the ears. Other signs include body tension, stretching, excessive hair loss, little or no exercise, low body posture, weight regain, trembling/trembling, penis tenting, paw sweating, glabellar tightening, barking, howling, and howling. When stressed, dogs typically experience altered behavior. Common behaviors commonly induced by stress include restlessness, under or over sleep, jumping/excessive alertness, irritability, excessive self-grooming, disruptive behavior, loss of appetite, compulsive/compulsive behavior, inability to concentrate on attention, excessive activity, increased defecation and vomiting and diarrhea, and the like.

There is a need for methods and compositions for reducing elevated 4-EPS levels, particularly in canines. There is a need for methods and compositions for treating or lessening the severity of elevated canine anxiety levels. There is a need for methods and compositions for treating or lessening the severity of elevated canine stress levels.

Disclosure of Invention

Methods for treating anxiety or stress in an animal are provided. The method comprises administering to the animal an effective amount of soy protein and vitamin C.

Methods for reducing elevated 4-EPS levels in animals with elevated 4-EPS levels are provided. The method comprises administering to the animal an effective amount of soy protein and vitamin C.

Methods for preventing an increase in 4-EPS levels in an animal are provided. The method comprises administering to an animal at risk of having an elevated level of 4-EPS an effective amount of soy protein and vitamin C.

Methods for promoting the growth of beneficial microorganisms and inhibiting the growth of non-beneficial microorganisms in a microbiome of an animal are provided. The method comprises administering to the animal an effective amount of soy protein and vitamin C.

Compositions for treating anxiety or stress in an animal are provided. The composition includes an effective amount of soy protein and vitamin C.

Compositions for reducing elevated 4-EPS levels in animals with elevated 4-EPS levels are provided. The composition includes an effective amount of soy protein and vitamin C.

Compositions for preventing elevated levels of 4-EPS in an animal are provided. The composition includes an effective amount of soy protein and vitamin C.

Compositions for promoting the growth of beneficial microorganisms and inhibiting the growth of non-beneficial microorganisms in the microbiome of an animal are provided. The composition includes an effective amount of soy protein and vitamin C.

Detailed Description

The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.

As used herein and in the appended claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.

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

The term "dog" encompasses those dogs that are companion animals, such as domestic dogs (Canis familiaris), working dogs (working dogs), and the like. The term dog is synonymous with the term canine.

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

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

"daily nutrient intake" and "total daily nutrient intake" refer to the amount of dry matter intake per day. That is, the weight of water is excluded when calculating the amount of nutrients consumed per day. In the case of food and food ingredients containing water/moisture, dry matter means all matter in the sample except water, including protein, fiber, fat, minerals, etc. Dry matter weight is the total weight minus the weight of any water. The daily dry matter intake is calculated as the total daily nutrient intake excluding all water. For example, the amount of an ingredient that is a particular percentage of the daily nutritional intake refers to the amount of the ingredient in dry matter (i.e., excluding all water) relative to the total amount of dry matter consumed during the day (also excluding all water). The skilled person will readily recognize and understand the amounts and percentages of nutrients expressed as dry matter, dry matter weight and dry matter percentage. Since foods, whether wet, moist or dry, generally contain a certain amount of water, the water component of such foods is excluded when calculating the daily dry matter intake. To calculate the total daily nutrient intake as daily dry matter intake, water was excluded. To calculate the percentage of ingredients of the total daily intake on a dry matter basis, water is removed from the total intake to obtain the total daily dry matter intake, and the percentage of ingredients is based on the amount of ingredients present in dry matter.

The composition useful in the method may be a pet food composition, such as a dog food composition. Alternatively, the soy protein and vitamin C may be administered as a supplement, snack, or toy, or otherwise not incorporated into the food provided to the animal for daily nutritional intake.

In some preferred embodiments, the animal is a canine and the method comprises administering to the canine an effective amount of soy protein and vitamin C daily. An effective amount of soy protein administered to canines daily is 3.7-6.9%, and in some embodiments 4.8-5.8%, and in some embodiments 5.3% of the daily nutrient intake. The effective amount of vitamin C administered to the canine daily is 104.8 to 148.2ppm, and in some embodiments 119.1 to 137.9ppm, and in some embodiments 126.5ppm of vitamin C per day of nutritional intake based on daily nutritional intake. The composition is preferably a dog food composition comprising an effective daily amount of soy protein and vitamin C.

Compositions and methods for treating anxiety or stress in animals, particularly companion animals such as felines and canines, are provided. 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 levels of 4-EPS. The compositions and methods are useful for reducing elevated 4-EPS levels in animals having elevated 4-EPS levels, such as companion animals, particularly canines. In some embodiments, compositions and methods for treating canine anxiety or canine stress in canines.

As used herein, the term "treating" 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 canines with symptoms of anxiety, treatment of the canines with anxiety refers to elimination of symptoms, prevention or slowing of progression of symptoms, reduction in severity of symptoms, and prevention of symptoms. Treatment to initially eliminate, arrest, slow progression of, or reduce severity of symptoms may continue, and continued treatment may further eliminate, arrest, slow progression of, or reduce severity of symptoms and/or prevent relapse or progression of symptoms or reduce severity of further progression of symptoms. In some embodiments, the canine can be identified as having anxiety symptoms prior to treating the canine for anxiety. In some embodiments, anxiety can be treated in canines without the need to identify anxiety symptoms prior to treatment. In some embodiments, the canine can be identified as having a predisposition to suffer from or develop anxiety prior to treatment for anxiety. In some embodiments, the canine can be identified as having an elevated level of 4-EPS prior to treatment for anxiety.

As used herein, the term "treatment" with respect to stress and stress disorders refers to therapeutic and/or prophylactic activity. In canines having symptoms of stress or stress disorder, treatment of the canine stress refers to elimination of symptoms, arresting or slowing the progression of symptoms, reducing the severity of symptoms, and preventing symptoms. Treatment to initially eliminate, arrest, slow progression of, or reduce severity of symptoms may continue, and continued treatment may further eliminate, arrest, slow progression of, or reduce severity of symptoms and/or prevent relapse or progression of symptoms or reduce severity of further progression of symptoms. In some embodiments, prior to treating the canine for stress, the canine can be identified as having symptoms of a stress or stress disorder. In some embodiments, the canine can be treated for stress or a stress disorder without the need to identify anxiety symptoms prior to treatment. In some embodiments, the canine can be identified as having a predisposition to suffer from or develop a stress or stress disorder prior to treatment of the stress or stress disorder. In some embodiments, the canine can be identified as having an elevated level of 4-EPS prior to treatment of stress or stress disorder.

As used herein, the term "treatment" with respect to promoting the growth of beneficial microorganisms and inhibiting the growth of detrimental microorganisms refers to therapeutic and/or prophylactic activity. In canines having reduced levels of beneficial microorganisms and increased levels of harmful microorganisms, a treatment for preventing the levels of beneficial and harmful microorganisms or promoting the growth of beneficial microorganisms and inhibiting the growth of harmful microorganisms. Prior to initiation of treatment, canines were identified as being prone to inhibit the growth of beneficial microorganisms and to promote the growth of harmful microorganisms. Treatment that initially promotes the growth of beneficial microorganisms and inhibits the growth of harmful microorganisms in animals with elevated levels of harmful microorganisms and reduced levels of beneficial microorganisms increases the levels of beneficial microorganisms and reduces the levels of harmful microorganisms to a healthier equilibrium and thereafter continues the treatment to maintain the levels. In some embodiments, the canine can be identified as having an elevated level of harmful microorganisms and a reduced level of beneficial microorganisms prior to treatment of canine stress. In some embodiments, canines can be treated without identifying an animal with an elevated level of a harmful microorganism and a reduced level of a beneficial microorganism.

As used herein, the terms "treatment of elevated 4-EPS", "treating elevated 4-EPS" and "treating elevated 4-EPS" refer to a therapeutic and/or prophylactic activity of reduced levels of 4-EPS. In canines with elevated 4-EPS levels, "treatment of elevated 4-EPS," "treating elevated 4-EPS," and "treating elevated 4-EPS" refer to decreasing elevated 4-EPS levels. Treatment may reduce elevated 4-EPS levels to normal, non-elevated levels or to reduced elevated 4-EPS levels. After decreasing elevated 4-EPS levels, the treatment may prevent elevated 4-EPS levels or reduce the severity of further development of elevated 4-EPS levels. In canines that do not have an elevated level of 4-EPS, "treatment of elevated 4-EPS," "treating elevated 4-EPS," and "treating elevated 4-EPS" refer to preventing or reducing the level of 4-EPS, and preventing the development of elevated 4-EPS levels or reducing the severity of the development of elevated 4-EPS levels. In some embodiments, the canine can be identified as having elevated 4-EPS by measuring the level of 4-EPS prior to treatment of 4-EPS. In some embodiments, canines with elevated 4-EPS can be treated without measuring 4-EPS levels prior to treatment. In some embodiments, canines can be identified as prone to having elevated 4-EPS prior to treatment of 4-EPS. Canines identified as predisposed to having elevated 4-EPS may have elevated 4-EPS when treated, in which case the treatment is therapeutic or may not have elevated 4-EPS, in which case the treatment is prophylactic or may be carried out without determination of 4-EPS levels. In some embodiments, canines can be identified as predisposed to having elevated 4-EPS, with or without measuring 4-EPS levels, prior to initiation of treatment.

As used herein, the terms "effective amount (an effective)", "effective amount (effective amount)", and the like refer to an amount of soy protein and vitamin C effective to achieve a particular biological result, i.e., the treatment of elevated levels of 4-EPS, anxiety, stress, and levels of beneficial and harmful microorganisms in the microbiome. In particular embodiments, an effective amount of the composition will be administered for a time sufficient to effect treatment. In particular embodiments, the methods comprise administering and consuming a composition comprising vitamin C and soy protein for a period of time sufficient to result in effective treatment and maintenance. An effective amount can be based on several factors, including the desired weight, age, sex, activity level of the dog, the metabolizable energy of the composition, and the frequency with which the composition is fed, e.g., once, twice, or three times daily, as well as other compositions fed to the dog. In some embodiments, an effective amount refers to the amount of soy protein and vitamin C administered based on total nutrient intake, wherein the amount of soy protein comprises 3.7-6.9% of the total nutrient intake per day and the amount of vitamin C comprises 104.8-148.2ppm of the total nutrient intake per day. In some embodiments, an effective amount refers to a pet food comprising 3.7-6.9% soy protein and 104.8-148.2ppm vitamin C on a dry matter basis of total nutritional intake per day. That is, the amount of food suitable to meet all of the daily nutritional and energy requirements of the canine subject contains 3.7-6.9% soy protein and 104.8-148.2ppm vitamin C on a dry matter basis.

In some embodiments, an effective amount refers to an amount of soy protein and vitamin C so administered based on total nutrient intake, the amount of soy protein being 4.8-5.8% of the total nutrient intake per day, and the amount of vitamin C being 119.1-137.9ppm of the total nutrient intake per day. In some embodiments, an effective amount refers to a pet food comprising 4.8-5.8% soy protein and 119.1-137.9ppm vitamin C on a dry matter basis of total nutritional intake per day. That is, the amount of food suitable to meet all of the daily nutritional and energy requirements of the canine subject contains 4.8-5.8% soy protein and 119.1-137.9ppm vitamin C on a dry matter basis.

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

In some embodiments, a "food," "food composition," or "pet food composition" can be a nutritionally complete diet of an animal, such as a dog, to which it is fed.

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

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

The food composition may be provided to an animal, such as but not limited to a pet, in the form of a pet food. Pet owners have access to various commonly known types of pet foods. Pet food options include, but are not limited to, wet pet food, semi-moist pet food, dry pet food, and pet treats. The moisture content of wet pet foods is typically greater than about 65%. Semi-moist pet foods typically have a moisture content of between about 20% and about 65% and may contain humectants, potassium sorbate, and other ingredients to prevent microbial growth (bacteria and mold). Dry pet foods such as, but not limited to, food kibbles typically have a moisture content of less than about 15%. Pet treats may typically be semi-moist chewable treats; any form of dry snack, chewable bone or baked extruded or stamped snack; a confectionery snack; or other types of snacks known to those skilled in the art.

As used herein, the term "kibble" or "food kibble" refers to granular, pellet-like components of animal feed, such as dog and cat feed. In some embodiments, the moisture or water content of the food coarse abrasive particles is less than 15% by weight. The texture of the food coarse grits can range from hard to soft. The internal structure of the food coarse abrasive particles can range from expanded to densified. The food coarse abrasive particles may be formed by an extrusion process or a baking process. In non-limiting examples, the food kibbles can have a uniform internal structure or a varying internal structure. For example, the food coarse abrasive particle may comprise a core and a coating to form a coated coarse abrasive particle. It should be understood that when the term "kibble" or "food kibble" is used, the term can refer to either uncoated kibble or coated kibble.

As used herein, the term "extrusion" or "extrusion" refers to a process of sending a pre-conditioned and/or prepared mixture of ingredients through an extruder. In some embodiments of extrusion, the food grits are formed by an extrusion process, wherein a kibble dough (comprising a mixture of wet and dry ingredients) can be extruded under heat and pressure to form the food grits. Any type of extruder may be used, examples of which include, but are not limited to, single screw extruders and twin screw extruders. Lists of sources, ingredients, and components are listed as described below such that combinations and mixtures thereof are also contemplated and are within the scope herein.

As contemplated herein, compositions are intended to encompass, but not be limited to, nutritionally complete and balanced animal food compositions. A "nutritionally complete diet" is a diet that contains sufficient nutrients to maintain healthy dogs in a healthy diet. Those skilled in the art are familiar with nutritionally complete and balanced pet food compositions, such as pet food compositions for canines. For example, materials suitable for nutritionally complete and balanced animal feed compositions, such as nutrients and ingredients and their recommended amounts, can be found, for example, in official publications (2012) of the american feed management association (AAFCO) of atlanta, georgia.

It is contemplated that when feeding a dog a diet comprising effective amounts of vitamin C and soy protein, the preferred method comprises feeding the dog a diet comprising vitamin C and soy protein. In other embodiments, feeding a dog a diet comprising effective amounts of vitamin C and soy protein is accomplished by administering vitamin C and soy protein to the dog as a supplement or treat. Whether delivered as a pet food composition, as a separate supplement, or as a treat, providing vitamin C and soy protein to a dog by any means is considered feeding the dog a diet including effective amounts of vitamin C and soy protein.

As used herein, the term "supplement" includes, but is not limited to, a feed used with another feed to improve the nutritional balance or performance of the animal's total diet. Supplements include, but are not limited to, compositions that are fed undiluted as a supplement to other feeds, compositions that provide a free choice with other parts of the animal's ration that are available separately, or compositions that are diluted and mixed with the animal's regular feed to produce a complete feed. The AAFCO guidelines, for example, contain discussions related to supplements in official publications (2012) of the american feed management association (AAFCO) of atlanta, georgia. Supplements may be in various forms, including, for example, powders, liquids, syrups, pills, encapsulated compositions, and the like.

The diet can include vitamin C and soy protein in amounts effective to reduce elevated 4-EPS levels in the canine. A diet including vitamin C and soy protein can be used to treat anxiety in canines. A diet including vitamin C and soy protein can be used to treat stress in canines. A diet including vitamin C and soy protein can be used to promote the growth of beneficial microorganisms and inhibit the growth of harmful microorganisms in the microbiome of canine subjects, particularly the microbiome of the gastrointestinal tract.

Compositions and formulations

Application of the methods outlined above has identified an effective amount of soy protein and vitamin C that provide significant benefit to dogs identified as prone to having elevated 4-EPS levels and thus an increased risk of developing anxiety, an increased risk of developing anxiety stress, and an increased risk of inhibiting the growth of beneficial microorganisms and promoting the growth of detrimental microorganisms in the microbiome of canines, particularly the gut microbiome. In some embodiments, the effective amount of soy protein and vitamin C are components that have been combined with other ingredients to provide a nutritionally complete diet. In some embodiments, the food product is a nutritionally complete diet for adult canines. In a particular aspect, the food product is a nutritionally complete diet formulated for adult companion canines.

In some embodiments, the compositions comprise a food composition suitable for consumption by a companion animal, particularly a dog, comprising an effective amount of vitamin C and soy protein in combination with protein and/or fat and/or carbohydrate. In some embodiments, for example, a nutritionally complete and balanced dog food composition may include, in addition to vitamin C and soy protein: 4 to 90 wt.%, 4 to 75 wt.%, 5 to 75 wt.%, 10 to 60 wt.% protein, or 15 to 50 wt.% protein, based on the total weight of the composition on a dry matter basis; 0 to 90 wt%, 2 to 80 wt%, 5 to 75 wt% and 10 to 50 wt% carbohydrate, based on the total weight of the composition on a dry matter basis; and from 2 wt% to 60 wt%, from 5 wt% to 50 wt%, and from 10 wt% to 35 wt% fat, by total weight of the composition on a dry matter basis. In some embodiments, for example, a nutritionally complete and balanced dog food composition may further contain from 0% to 15% or from 2% to 8% by weight of other vitamins and minerals, antioxidants, and other nutrients, such as amino acids that support the nutritional needs of the animal, in addition to vitamin C and soy protein. Vitamin C can be administered in such diets as ascorbic acid and its various derivatives, such as calcium phosphate salts, cholesteryl salts, 2-monophosphate, and the like, which will act with vitamin C-like activity upon ingestion by the pet. It may be in any form, such as liquid, semi-solid, solid and heat stable forms.

Sources of protein, carbohydrate, fat, vitamins, minerals, balancing agents, and the like suitable for inclusion in the compositions, and in particular in the food products to be administered in the methods provided herein, may be selected from those conventional materials known to those of ordinary skill in the art.

In addition to the effective amount of soy protein, in some embodiments, the protein useful as an ingredient of the food composition can include proteins from animal sources, such as animal proteins, including mammalian, avian proteins, reptilian, amphibian, fish, invertebrate proteins, and combinations thereof; for example, from any of cattle, sheep, pigs, goats, deer, rabbits, horses, kangaroos, milk, curd, whey or blood thereof, as well as internal tissues and organs, such as smooth muscle, striated muscle, liver, kidney, intestine or heart; chickens containing internal tissues and organs such as smooth muscle, striated muscle, liver, kidney, intestine or heart and chicken eggs, additional sources of avian protein encompass turkeys, geese, ducks, ostriches, quail, pigeons, eggs thereof, and internal tissues and organs such as smooth muscle, striated muscle, liver, kidney, intestine or heart; the source of amphibians comprises frogs or lizards, and the source of reptile proteins comprises alligator, lizard, tortoise, and snake; sources of fish protein include catfish, herring, salmon, tuna, bluefish, cod, halibut, trout, swordfish, and eggs thereof; and the invertebrate protein source comprises lobster, crab, clam, mussel or oyster and combinations thereof, meat protein isolate, whey protein isolate, egg protein and mixtures thereof, and vegetable sources such as corn gluten meal, wheat gluten and mixtures thereof.

In some embodiments, carbohydrates useful as ingredients in food compositions may include, but are not limited to, one or more of the following: corn, whole yellow corn, sorghum, wheat, barley, rice, millet, beer rice, oat groats (oat groat), and polysaccharides that metabolize energy when hydrolyzed (e.g., starch and dextrin) and sugars (e.g., sucrose, lactose, maltose, glucose, and fructose). Examples of additional carbohydrate sources suitable for inclusion in the compositions disclosed herein include fruits and vegetables.

Fats that may be used as ingredients in the food composition may be from any source, such as, but not limited to, poultry fat, tallow, lard, choice white fats, soybean oil, corn oil, canola oil, sunflower oil, mixtures thereof, and the like. The fat may be incorporated completely within the food composition, deposited on the exterior of the food composition, or a mixture of both methods.

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

In some embodiments, the food composition further comprises one or more amino acids, such as, but not limited to, arginine, histidine, isoleucine, leucine, lysine, methionine (including DL-methionine and L-methionine), phenylalanine, threonine, tryptophan, valine, taurine, carnitine, alanine, aspartic acid, cystine, glutamic acid, glutamine, glycine, proline, serine, tyrosine, and hydroxyproline.

In some embodiments, the food composition further comprises one or more fatty acids, such as, but not limited to, lauric acid, myristic acid, palmitic acid, palmitoleic acid, heptadecanoic acid, heptadecadienoic acid (margarleic acid), stearic acid, oleic acid, linoleic acid, g-linolenic acid, a-linolenic acid, linoleic acid (stearidonic acid), arachidic acid, olefinic acid, DHGLA, arachidonic acid, EPA, behenic acid, erucic acid, docosatetraenoic acid, and DPA.

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.

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 comprises one or more minerals such as, but not limited to, calcium, phosphorus, potassium, sodium, chloride, iron, copper, manganese, zinc, iodine, selenium, cobalt, sulfur, fluorine, chromium, boron, and oxalate.

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

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

In some embodiments, the food composition further comprises a stabilizing substance, e.g., a substance that tends to increase the shelf life of the composition. Potentially suitable examples of such materials include, for example, preservatives, antioxidants, synergists and sequestrants, packaging gases, stabilizers, emulsifiers, thickeners, gelling agents, and humectants. Examples of emulsifiers and/or thickeners include, for example, gelatin, cellulose ethers, starch esters, starch ethers, and modified starches.

In some embodiments, the food composition further comprises additives for coloring, palatability, and nutritional purposes, including, for example, colorants; iron oxide, sodium chloride, potassium citrate, potassium chloride and other edible salts; a vitamin; a mineral; and a flavoring agent. The amount of such additives in the composition is typically up to 5% (based on the dry matter of the composition).

Preparation of the composition

The composition comprising vitamin C and soy protein can be prepared as a food suitable for consumption by dogs. These foods may have any consistency or moisture content; that is, the composition may be a moist, semi-moist, or dry food product. "moist" food products are typically food products having a moisture content of 60% to 90% or more. "dry" food products are typically food products having a moisture content of 3% to 11% and are typically manufactured in the form of small pieces or coarse abrasive particles. The moisture content of "semi-moist" food products is typically 25% to 35%. The food product may also comprise more than one consistency component, such as soft chewy meat-like particles or tablets, and coarse abrasive particles having an outer cereal component or coating and an inner "cream" component.

In some embodiments, the food product comprising vitamin C and soy protein can be prepared in a canned or wet form using conventional food preparation processes known to those of ordinary skill in the art. Typically, the ground animal proteinaceous tissue is mixed with other ingredients, such as cereal grains, suitable carbohydrate sources, fats, oils and balance ingredients, including special purpose additives such as vitamin and mineral mixtures, inorganic salts, cellulose, beet pulp and the like, and water in an amount sufficient for processing. The ingredients are mixed in a vessel suitable for heating while blending the components. The mixture is heated using any suitable means, such as direct steam injection or using a vessel equipped with a heat exchanger. After all the ingredients of the formulation were added, the mixture was heated to a temperature of 50 to 212 ° f. Although temperatures outside this range may be used, they may be commercially impractical without the use of other processing aids. When heated to the appropriate temperature, the material will typically be in the form of a thick liquid that is dispensed into a tank. The lid is closed and the container is sealed. The sealed can is then placed in conventional equipment designed for sterilization of the contents. Sterilization is typically accomplished by heating to a temperature above 230 ℃ for an appropriate time, depending on the temperature used, the nature of the composition, and related factors. The compositions and food products of the invention may also be added to or combined with food compositions before, during or after preparation.

In some embodiments, the food product may be prepared in a dry form using conventional processes known to those of ordinary skill in the art. Typically, dry ingredients including dried animal protein, plant protein, grain, and the like are ground and mixed together. Liquid or moist ingredients including fats, oils, water, animal proteins, water, etc. are added in combination with the dry material. The particular formulation, order of addition, combination, and methods and apparatus for combining the various ingredients can be selected from those known in the art. For example, in certain embodiments, the resulting mixture is processed into coarse abrasive particles or similar dry pieces that are formed using an extrusion process in which a mixture of dry and wet ingredients is subjected to machining at high pressure and temperature, forced through small openings or orifices, and cut into coarse abrasive particles, for example, with a rotating knife. The resulting kibbles can be dried and optionally coated with one or more topical coatings including, for example, flavors, fats, oils, powdered ingredients, and the like. The coarser grit may also be prepared from the dough by baking rather than extrusion, wherein the dough is placed in a mold prior to dry heat processing.

In preparing the composition, any ingredient may generally be incorporated into the composition during processing of the formulation, for example during and/or after mixing of the other components of the composition. The distribution of these components in the composition can be accomplished in a conventional manner. In certain embodiments, the ground animal and/or poultry protein tissue is mixed with other ingredients including nutritional balancing agents, inorganic salts, and may further include cellulose, beet pulp, bulking agents, and the like, along with sufficient water to be processed.

In some embodiments, the composition is formulated to make it easier to chew. In particular embodiments, the compositions and foods are formulated to address specific nutritional differences between species and breeds of animals, as well as one or more of attributes of the animals. For example, canine foods are typically formulated, e.g., based on life stage, age, size, weight, body composition, and breed.

In another embodiment, a snack comprising an effective amount of soy protein and vitamin C may be prepared by an extrusion or baking process, for example similar to the extrusion or baking process described below for dry foods, to provide an edible product. Treats comprise, for example, compositions administered to an animal to entice the animal to eat during a non-meal period. Treats may be nutritional, wherein the composition includes one or more nutrients, and may, for example, have a composition as described above for food. Non-nutritive snacks encompass any other snack that is non-toxic. The composition may be coated onto a snack, incorporated into a snack, or both.

In another embodiment, an animal toy is provided that is a chewable or edible toy. Such toys are generally prepared by coating any existing toy with an effective amount of soy protein and vitamin C. Thus, the toy comprises, for example, a chewable toy. Contemplated dog toys include, for example, artificial bones. In certain embodiments, the compositions of the present invention may form a coating on the surface of the toy or on the surface of a toy component, or the compositions may be incorporated partially or wholly throughout the toy, or both. Various suitable toys are currently marketed. See, for example, U.S. patent No. 5,339,771 (and references disclosed in U.S. patent No. 5,339,771). See also, for example, U.S. Pat. No. 5,419,283 (and the references disclosed in U.S. Pat. No. 5,419,283). It should be appreciated that the present invention contemplates partially edible toys (e.g., toys comprising plastic components) and fully edible toys (e.g., rawhides and various artificial bones). It should be further appreciated that the present invention contemplates toys for companion animals and particularly toys for cats or dogs.

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

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

Examples of the invention

Example 1

The microbial metabolite 4-ethylphenyl sulphate (4-EPS) is associated with stress and anxiety. Reduction of 4-EPS levels has been shown to alleviate these symptoms.

A study was conducted with 30 adult dogs (between 4 and 10 years of age) showing that the optimal combination of vitamin C and soy protein reduces the circulating levels of the stress-related microbial metabolite 4-ethylphenyl sulfate (4-EPS).

Different levels of soy protein (0 grams to 24 grams) were combined with different levels of vitamin C (10.24mg to 44.37 mg). This resulted in different vitamin C and soy protein intakes per dog.

Blood was collected to determine plasma metabolomics profiles. The level of 4-EPS in plasma can be measured by a commercial laboratory (Metabolon, Durham, NC, USA, Dalleem, N.C.). The extracted supernatant was separated and run on a gas and liquid chromatography mass spectrometer platform. The peaks of 4-EPS are known, and the area under each peak can be normalized to known samples (see also: Evans, A.M. et al (2009), Integrated, non-targeted ultra performance liquid chromatography/electrospray ionization tandem mass spectrometry platform (Integrated, non-acquired, high performance chromatography/electrophoresis ionization, etc.) for identification and relative quantification of small molecule complement of biological systems analytical chemistry (anal. chem. 81, 6656-6667). Gas chromatography (for hydrophobic molecules) and liquid chromatography (for hydrophilic molecules) are used to identify and provide relative quantification of metabolites such as 4-EPS present in plasma samples. (see also: Ballet, C.et al (2018), New enzyme and Mass Spectrometry methods for the selective study of gut microbiota-derived metabolites (New enzyme and Mass Spectrometry methods for the selective uptake of gut microbiota-derived metabolites), "chemistry science (chem. Sci.) 9,6233- effect of an organic solvent AST-120by liquid chromatography/chromatography mass spectrometry J chromatography B analytical technology Biomed Life Sci 878:2997 3002. )

Circulating 4-EPS levels were determined and the correlation of soy protein and vitamin C intake with blood 4-EPS levels was evaluated.

Dogs that tend to have high 4-EPS may benefit from consuming foods containing specific levels of vitamin C and soy protein. A matched pair analysis comparing 4-EPS levels per dog after food consumption showed a significant reduction in 4-EPS due to the added vitamin C and soy protein (P ═ 0.04).

The daily intake of vitamin C and soy protein resulting in low levels of 4-EPS is shown in table 1. The potential of different combinations of soy protein and vitamin C to reduce circulating 4-EPS levels in adult dogs was evaluated. With increasing vitamin C and soy protein intake, circulating 4-EPS levels increased and then surprisingly decreased with increasing intake. After consuming 10 g of soy protein and 23.9mg of vitamin C per day, the lowest level of 4-EPS was detected (Table 1). The average intake of adult dogs was 188.9 grams. Thus, consumption of a food containing about 5.3% soy protein in combination with 126.5ppm vitamin C on a dry matter basis will result in the lowest 4-EPS level. After consumption of 24 g soy protein and 44.4mg vitamin C, the highest level of 4-EPS was detected, 1.22468. The 4-EPS levels in pets are higher than average after consumption of low or no soy protein (0-3 grams) and 10.2-14.3mg vitamin C or high soy protein (18-24 grams) and 34.8-44.4mg vitamin C. Low 4-EPS levels are achieved by consuming 7-13g (3.7-6.9%) soy protein and 19.8-28mg (104.8-148.2ppm) vitamin C daily. When 9-11 g (4.8-5.8%) soy protein and 22.5-25.3mg (119.1-137.9ppm) vitamin C were consumed daily, the 4-EPS level was lower. The lowest level of 4-EPS was observed when 10 g (5.3%) soy protein and 23.9mg (126.5ppm) vitamin C were consumed daily.

Table 1: combination of soy protein and vitamin C to reduce circulating 4-EPS levels

Soy protein and vitamin C, when provided in effective amounts, reduce circulating 4-EPS levels. An anti-stress food for pets can be formulated by including an effective amount of soy protein and vitamin C, thereby reducing the blood level of microbial toxin 4-EPS, which is associated with stress, anxiety and brain injury when microbial toxin increases. Such pet foods thereby address stress-related issues associated with elevated circulating 4-EPS levels in pets.

Example 2

The following compositions are based on total nutrition provided daily.

In some embodiments, the amount of soy protein is equal to 3.7-6.9% and the amount of vitamin C is equal to 104.8-148.2ppm, based on the total weight of the composition on a dry matter basis. In some embodiments, the composition comprises chicken in an amount of 5% to 25%, egg protein in an amount of 4% to 15%, corn gluten meal in an amount of 6% to 20%, vegetables in an amount of 0.5% to 2% thereof, fruit in an amount of 0.5% to 2%, and carbohydrate selected from the group consisting of millet, beer rice, oat groats, and combinations thereof in an amount of 5% to 50%, by total weight of the composition on a dry matter basis.

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

In certain embodiments, the composition may include chicken in an amount of 5%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, or 25% by total weight of the composition on a dry matter basis. In certain embodiments, the composition may include egg protein in an amount of 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15% by total weight of the composition on a dry matter basis. In certain embodiments, the composition may include corn gluten meal in an amount of 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% by total weight of the composition on a dry matter basis. In certain embodiments, the composition may comprise the vegetable source in an amount of 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1.9%, or 2.0% by total weight of the composition on a dry matter basis. In certain embodiments, the composition may include the fruit source in an amount of 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1.9%, or 2.0% by total weight of the composition on a dry matter basis. In certain embodiments, the composition may comprise a carbohydrate selected from the group consisting of millet, beer rice, oat groats, and combinations thereof in an amount of 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by total weight of the composition on a dry matter basis. In particular aspects of these embodiments, the compositions of the invention may comprise a dry weight of the carbohydrate source within a range defined by any two of these values as endpoints.

Example 3

Table 2 describes certain examples with composition ratios (% by weight of dry matter of the component compositions).

TABLE 2

A daily diet including vitamin C and soy protein can provide benefits to dogs identified as having stress. In some embodiments, the method comprises identifying the dog as having or suspected of having stress, a stress disorder, or exhibiting symptoms of stress or a stress disorder, and feeding the dog a daily diet comprising vitamin C and soy protein.

Example 4

Table 3 describes the ingredients used in certain examples with the composition proportions (% by weight of dry matter of the component compositions).

TABLE 3

Example 5

Table 4 describes the ingredients used in certain examples with composition proportions (% by dry matter weight of the component compositions).

TABLE 4

Example 6

Table 5 describes the ingredients used in certain examples with the composition proportions (% by weight of dry matter of the component compositions).

TABLE 5

Example 7

Table 6 describes the ingredients used in certain examples with composition proportions (% by dry matter weight of the component compositions).

TABLE 6

Composition (I)	w/w％
		Soy protein	3.7-6.9
Vitamin C	0.012-0.034
		Beer rice	—
Chicken powder	6.00-7.00
		Pea, protein concentrate	7.00-8.00
Coarse cellulose	3.00-4.00
		Chicken, dry 10% ash	5.00-6.00
Barley, pearly, split	18.00-20.00
		Chicken, ground, fresh	7.00-8.00
Flax, seeds, whole body	2.00
		Preserved coconut oil	4.00
Chicken, liver, digesta, optimizing agent LDPE H	3.00
		Lactic acid	1.50
Methionine, dl	0.64
		Potassium chloride	0.50
Sodium chloride, iodide	0.60
		Fish oil, TG, 18/12, NP	0.50
Calcium carbonate	0.30
		Choline chloride, liquid, 70%	0.25
Carnitine, 1, 10%	0.30
		Vitamin E, oil, 29%	0.17
Minerals, premixes, 2305	0.08
		Taurine	0.06
Oat grains	10.00
		Buckwheat grain	6.92
Pea, bran, meal	5.00
		The concentration of the tomato, the pomace,	5.00
beet pulp, ground, fine	3.00

Example 8

Table 7 describes the ingredients used in certain examples with composition proportions (% by dry matter weight of the component compositions).

TABLE 7

Example 9

Table 8 describes the ingredients used in certain examples with composition proportions (% by dry matter weight of the component compositions).

TABLE 8

Example 10

Table 9 describes the ingredients used in certain examples with composition proportions (% by dry matter weight of the component compositions).

TABLE 9

Composition (I)	w/w％	w/w％	w/w％	w/w％	w/w％
						Soy protein	3.7-6.9	3.7-6.9	3.7-6.9	3.7-6.9	3.7-6.9
Vitamin C	0.012-0.034	0.012-0.034	0.012-0.034	0.012-0.034	0.012-0.034
						Coconut oil	Up to 14.2	Up to 7.1	Up to 14.2	Up to 13.0	Up to 13.0
Protein	Up to 19.7	Up to 24.7	Up to 24.7	Up to 24.8	Up to 24.8
						Fat	Up to 20.6	Up to 16.9	Up to 16.9	Up to 22.0	Up to 22.0
Carbohydrate compound	Up to 53.8	Up to 51.0	Up to 51.0	Up to 46.3	Up to 27.6
						Coarse fiber	Up to 0.37	Up to 2.6	Up to 2.6	Up to 1.4	Up to 21.0

Claims

1. A method for treating anxiety or stress in an animal comprising administering to the animal an effective amount of soy protein and vitamin C.

2. The method of claim 1 wherein the animal is administered soy protein at 3.7-6.9% of daily nutrient intake and vitamin C at 104.8-148.2ppm of daily nutrient intake.

3. The method of claim 1 wherein the animal is administered a food composition comprising soy protein and vitamin C, wherein the soy protein comprises 3.7-6.9% of daily nutritional intake and the level of vitamin C comprises 104.8-148.2ppm of daily nutritional intake.

4. The method of claim 1 wherein the animal is administered a food composition comprising soy protein and vitamin C, wherein the soy protein comprises 4.8-5.8% of daily nutritional intake and the level of vitamin C comprises 119.1-137.9ppm of daily nutritional intake.

5. The method of claim 1 wherein the animal is administered a food composition comprising soy protein and vitamin C, wherein the soy protein comprises 5.3% of daily nutritional intake and the level of vitamin C comprises 126.5ppm of daily nutritional intake.

6. The method of any one of claims 1-5, wherein the animal is a canine.

7. The method of claim 6 wherein the canine is identified as having an elevated level of 4-ethylphenylsulfate.

8. The method of claim 6 wherein the canine has been previously identified as having canine anxiety.

9. The method of claim 6 wherein the canine has been previously identified as having canine stress symptoms.

10. A food composition comprising an effective amount of soy protein and an effective amount of vitamin C to treat anxiety, stress or stress disorders in an animal, wherein the effective amount of soy protein is 3.7-6.9% and the effective amount of vitamin C is 104.8-148.2ppm, on a dry matter weight percent basis.

11. The food composition of claim 10 wherein the effective amount of soy protein is 4.8-5.8% and the effective amount of vitamin C is 119.1-137.9ppm, as a weight percentage of dry matter.

12. The food composition of claim 10, wherein the effective amount of soy protein is 5.3% and the effective amount of vitamin C is 126.5ppm as a weight percent of dry matter.

13. The food composition of any one of claims 10-12 wherein the food composition is a canine food composition.