MCT-BASED NUTRITIONAL BLEND TO PROVIDE HEALTH BENEFITS IN ANIMALS.

Abstract

The present invention relates to a method for producing a glycosylated product from glycoside intermediates, the method being characterized in that it comprises the steps of: providing a bacterial cell intracellularly expressing one or more UDP-dependent glucosyltransferase enzymes (UGT enzymes), wherein the UGT enzymes glycosylate steviol glycoside substrates, wherein the bacterial cell exhibits overexpression of phosphoglucomutase (pgm) and UTP-glucose-1-phosphate uridyltransferase, and wherein the bacterial cell exhibits a deletion, inactivation, or reduced expression of one or more genes encoding UDP-glucose consuming enzymes, selected from: a UDP-sugar hydrolase, an enzyme responsible for the biosynthesis of UDP-galactose from UDP-glucose, a trehalose-6-phosphate synthase, and a UDP-glucose-6-dehydrogenase;incubate the bacterial strain with the glycoside intermediates, wherein the glycoside intermediates are steviol glycosides from stevia leaf extract, and recover the glycosylated product.

Description

DETAILED DESCRIPTION Definitions Some definitions are provided below. However, the definitions may be located in the “Modalities” section below, and the title “Definitions” above does not mean that such descriptions in the “Modalities” section are not definitions. As used in this description and the accompanying claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly indicates otherwise. Thus, for example, a reference to “an ingredient” or “the ingredient” includes two or more ingredients. The term “and / or” used in the context of X and / or Y should be construed as X, or “Y, or X and Y.” When used herein, the term “example,” particularly when preceding a list of terms, is given simply by way of example and illustration and should not be considered exclusive or integral. As used herein, “approximately” is understood to refer to numbers within a range, for example, the range of -10% to +10% of the reference number, preferably -5% to +5% of the reference number, more preferably -1% to +1% of the reference number, with the maximum preference of -0.1% to +0.1% of the reference number. A range that is “between” two values ​​includes those two values. Furthermore, all numerical ranges herein should be understood to include every whole number, whole or fractional, within the range. These numerical ranges should also be interpreted as providing support for a claim directed to any number or subset of numbers within that range. For example, a description of 1 to 10 should be interpreted as supporting a range of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, and so on. All percentages expressed in this description are by weight of the total weight of the composition on a dry matter basis unless otherwise stated. When pH is mentioned, the values ​​correspond to pH measured at 25 °C using standard equipment. The terms “food,” “food product,” and “food composition” mean a product or composition that is intended for ingestion by an animal and provides at least one nutrient to the animal. The term “pet food” means any food composition intended for consumption by a companion animal. Such food compositions may include main food, treats, drinks, supplements, etc. The term “pet” means a dog or a cat. As used in this description, the terms “cat” and “feline” may be used interchangeably. Similarly, the terms “dog” and “canine” may be used interchangeably. In one instance, the pet may be a cat. The term "aged" means that the animal is of advanced age, having exceeded 50% of the average lifespan for its particular species and / or breed within a species. For example, if the average lifespan for a certain breed of dog is 10 years, then a dog of that breed older than 5 years would be considered aged for the purposes of this description. Similarly, for example, if the average lifespan for a breed of cat is 15 years, then a cat of that breed older than 7.5 years would be considered "aged" for the purposes of this description. In one embodiment, the compositions and methods described in this invention include an adult animal, e.g., an adult dog or an adult cat. Animals such as dogs and cats are considered adults in the last 25% of their lives.As indicated in the present description, the life expectancy of a dog or cat depends on its size and / or breed, and an adult dog or adult cat can be determined based on the above calculation but using the numerical value of 75% in such a way that the age threshold exceeds 75% of the average life expectancy. “Wet food” means pet food that has a moisture content of approximately 50% to approximately 90%, and in one aspect, approximately 70% to approximately 90%. “Dry food” means pet food that has a moisture content of less than approximately 20%, and in one aspect, less than approximately 15%, and in one specific aspect, less than approximately 10%. “Semi-moist food” means pet food that has a moisture content of approximately 20% to approximately 50%, and in one aspect, approximately 25% to approximately 35%. “Kibble” means pieces of dry or semi-moist pet food that may be pellet-shaped or any other shape.Non-limiting examples of kibble include particulates; pellets; pieces of pet food, dried meat, meat substitute, vegetables, and combinations thereof; and pet snacks such as slices of dried meat or vegetables, leather, and biscuits. The compositions described herein may lack any element not specifically described herein. Therefore, a description of a modality using the term “comprising” includes a description of the modalities “consisting essentially of” and “consisting of” the identified components. Similarly, the methods described herein may lack any step not specifically described herein. Therefore, a description of a modality using the term “comprising” includes a description of the modalities “consisting essentially of” and “consisting of” the identified steps. Furthermore, the description of some steps as “optional” does not imply that the other steps not explicitly described as optional are necessarily required. Any modality described in this description may be combined with any other modality described in this description. Prevention includes reducing the risk and / or severity of a condition or disorder. The terms treatment, treat, and alleviate include both prophylactic and preventive treatment (which prevents and / or delays the development of an objective pathological condition or disorder) and curative, therapeutic, or disease-modifying treatment, which includes therapeutic measures that cure, delay, lessen the symptoms, and / or halt the progression of a diagnosed pathological condition or disorder; and the treatment of patients at risk of contracting a disease or suspected of having contracted a disease, as well as patients who are ill or have been diagnosed with a disease or medical condition. The term does not necessarily imply that a subject is treated until full recovery.The terms “treatment” and “treat” also refer to the maintenance and / or promotion of health in an individual who does not suffer from a disease but who may be susceptible to developing an unhealthy condition. The terms “treatment,” “treat,” and “relieve” are also intended to include the enhancement or improvement in any other way of one or more primary prophylactic or therapeutic measures. The terms “treatment,” “treat,” and “relieve” are further intended to include the dietary management of a disease or condition or dietary management for the prophylaxis or prevention of a disease or condition. A treatment may relate to a patient or to a physician. The relative terms “enhanced”, “increased”, “enhanced” and the like refer to the effects of the composition described herein (a composition comprising a therapeutically effective amount of medium-chain triglycerides or a prophylactic dose of medium-chain triglycerides) in relation to a composition having a lower amount or lacking medium-chain triglycerides, but otherwise identical. The term “therapeutically effective amount” refers to an amount of a compound of the present invention that (i) treats or prevents the particular disease, condition, or disorder, (ii) alleviates, relieves, or eliminates one or more symptoms related to the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein. In one embodiment, the therapeutically effective amount may refer to the amount to treat any condition related to sarcopenia or muscle atrophy. The term “long-term administration” means periods of repeated administration or consumption longer than one month. Periods longer than two, three, or four months may be used for some modalities. Longer periods of more than 5, 6, 7, 8, 9, or 10 months may also be used. Periods exceeding 11 months or 1 year may also be used. The invention may also include extended periods of use, lasting 1, 2, 3, or more years. For certain aging animals, the animal may continue to consume regularly for the remainder of its life. This may sometimes be referred to as consumption over “extended” periods. The term “regular base” means at least monthly dosing with the formulas or consumption of the formulas and, in some cases, weekly dosing. In certain modalities, more frequent dosing or consumption may be used, such as two, three, or seven times per week. Still other modalities include regimens that comprise at least daily consumption. The person skilled in the technique will appreciate that the frequency of dosing will be a function of the formula being consumed or administered, and some formulas may require more or less frequent administration to maintain a desired level of hydration. A “medium-chain triglyceride” is a lipid in which three fatty acids are linked by ester bonds to a glycerol backbone, and at least two, and preferably all three, of the fatty acids are each between six and twelve carbons in length. The medium-chain fatty acids are caproic acid (comprising six carbon atoms or C6:0), caprylic acid (comprising eight carbon atoms or C8:0), capric acid (comprising ten carbon atoms or C10:0), and lauric acid (comprising twelve carbon atoms or C12:0). In one embodiment, the medium-chain fatty acids are found primarily (e.g., at least 98%) in the form of triglycerides.A composition comprising “lipids consisting essentially of medium-chain triglycerides” contains medium-chain triglycerides as at least 20% of the lipids, in some embodiments at least 30% of the lipids, in other embodiments at least 40% of the lipids, and in some embodiments at least 50% of the lipids in the composition. In one embodiment, the medium-chain fatty acids of the medium-chain triglycerides may include at least 50% caprylic acid of the total medium-chain fatty acids present. In another embodiment, the medium-chain fatty acids of the medium-chain triglycerides may include at least 90% caprylic acid of the total medium-chain fatty acids present. This description relates to compositions comprising medium-chain triglycerides and methods comprising administering the compositions to an animal to provide a health benefit. More specifically, this description relates to compositions comprising medium-chain triglycerides (MCTs) and, in some aspects, may optionally include one or more omega-3 fatty acids, antioxidants, or arginine. This description also relates to methods for treating sarcopenia or muscle wasting and to methods for increasing weight gain, increasing fat gain, or maintaining lean body mass in an animal in need by administering the present MCT compositions to the animal. The present inventors have discovered that the present MCT compositions can treat sarcopenia or muscle atrophy in an animal, as well as increase weight gain, increase fat gain, or maintain lean body mass in an animal in need. This effect may help treat animals suffering from cancer, AIDS, congestive heart disease, chronic obstructive pulmonary disease, kidney failure, severe burns, and cachexia. Accordingly, in a general modality, a method is provided for treating sarcopenia or muscle atrophy in an animal, as well as increasing weight gain, increasing fat gain, or maintaining lean body mass in an animal in need. The methods may comprise orally administering a composition comprising a therapeutically effective amount of medium-chain triglycerides to the animal. The methods may also include an identification stage for which treatment or a health benefit is sought. For example, the method may also include identifying an animal with sarcopenia or muscle atrophy. In other modalities, the method may also include identifying an animal that needs one of the following: increased weight gain, increased fat gain, or maintenance of lean body mass, and combinations thereof. Furthermore, in other modalities, the method may also include identifying an animal suffering from cancer, AIDS, congestive heart disease, chronic obstructive pulmonary disease, kidney failure, severe burns, and cachexia. The methods generally involve orally administering to the animal a composition comprising medium-chain triglycerides and optionally one or more omega-3 fatty acids, antioxidants, and / or an amino acid. In one embodiment, the composition may further comprise a component selected from the group consisting of an omega-3 fatty acid, antioxidants (including vitamin E, vitamin C, selenium, and / or polyphenols), arginine, and mixtures thereof. The composition may be a pet food, such as wet pet food, semi-moist pet food, or dry pet food, e.g., kibble. Medium-chain triglycerides (MCTs) generally range from approximately 0.5% to approximately 60% by weight of the composition. In one aspect, MCTs can range from approximately 1% to approximately 20% by weight of the composition. In other aspects, MCTs can range from approximately 1% to approximately 15% by weight, from approximately 1% to approximately 10% by weight, or from approximately 2% to approximately 10% by weight of the composition. MCTs can be prepared by any known process, such as direct esterification, redistribution, fractionation, and / or transesterification. For example, MCTs can be prepared from a vegetable oil source, such as coconut oil, by a redistribution process.The chain length and distribution can vary depending on the source oil. For example, MCTs containing 1–10% C6, 30–60% C8, 30–60% C10, and 1–10% C12 can be derived from palm oil and / or coconut oil. In some embodiments, at least a portion of the MCTs is provided by coconut oil, while in others, the composition does not contain coconut oil. MCTs containing at least approximately 95% C8 can be manufactured by semisynthetic esterification of octanoic acid to glycerin. In some embodiments of these, the remaining fatty acids are C6 and C10. For the purposes of this description, mixtures comprising MCTs with approximately 50% total C8 and / or approximately 50% total C10 are also useful. In one form, MCTs may include an MCT selected from the group consisting of caprylic acid, capric acid, and a mixture of these.In one form, MCTs may substantially include fatty acids that are caprylic acid (C8). For example, such MCTs may include those that have at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95%, at least 98%, or even 100% caprylic acid. Non-limiting examples of suitable omega-3 fatty acids include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and mixtures thereof. In one embodiment, omega-3 fatty acids may range from approximately 0.2% by weight to approximately 3% by weight of the composition. In some embodiments, omega-3 fatty acids are at least approximately 0.2% by weight, at least approximately 1.0% by weight, or at least approximately 2.0% by weight. In one embodiment, the omega-3 fatty acid may be selected from the group consisting of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and mixtures thereof. In some formulations, the composition can be administered to the pet for a period of at least one week, at least one month, at least two, three, four, five, or six months; and in some formulations, for at least one year. During this period, the composition can be administered to the dog at least one day per week, at least two days per week, at least three, four, five, or six days per week; or even seven days per week. The composition can be administered as a single dose per day or in multiple doses given separately throughout the day. In one formulation, the composition can be administered in an amount that provides approximately 0.001 g to 50 g of MCT / kg of the pet's body weight per day. In another formulation, approximately 0.1 g to 5 g of MCT / kg of the pet's body weight can be administered per day. In one specific instance, the animal may be a pet. In one aspect, the pet may be a cat. In one instance, the animal may be an adult or an elderly animal. In one aspect, the animal may be an adult cat. In another aspect, the animal may be an elderly cat. In one embodiment, the compositions described herein may be pet food compositions. The pet food compositions described herein may be any food formulated for consumption by a pet, such as a cat. In one embodiment, the pet food composition provides complete nutrition as defined by the Association of American Feed Control Officials (AAFCO) and is dependent on the type of animal for which the composition is intended (e.g., a cat). In another embodiment, the composition may be a supplement. Such a supplement may be added to a food composition, administered together with a food composition, or administered separately. As such, in some embodiments, the compositions herein may be complete and nutritionally balanced pet foods. Generally, pet food compositions may include protein, carbohydrates, fat, and ash. In various formulations, pet food compositions comprise approximately 15% to approximately 50% crude protein. In some formulations, such compositions may also comprise approximately 5% to approximately 40% fat. In other formulations, compositions may also comprise approximately 15% to approximately 60% carbohydrates. In still other formulations, the composition may also comprise approximately 0.1% to approximately 15% ash. Pet food composition may include meat, such as emulsified meat. Examples of suitable meat include poultry, beef, pork, lamb, and fish, especially those types of meat suitable for pets. Meat may include any additional part of an animal, including offal. Some or all of the meat may be provided as one or more meat meals, namely, meat that has been dried and ground to form substantially uniform particle size as defined by AAFCO. Additionally or alternatively, vegetable protein may be used, such as pea protein, corn protein (e.g., ground corn or corn gluten), wheat protein (e.g., ground wheat or wheat gluten), soy protein (e.g., soybean meal, soy concentrate, or soy isolate), rice protein (e.g., ground rice or rice gluten), and the like. The pet food compositions described herein may comprise one or more of a vegetable oil, a flavoring, a coloring, or water. Non-limiting examples of suitable vegetable oils include soybean oil, corn oil, cottonseed oil, sunflower oil, canola oil, peanut oil, safflower oil, and the like. In some embodiments, the lipids in the composition may consist of MCTs and one or more of any vegetable oil, any fish oil, the lipid from any meat, and any omega-3 fatty acids. Non-limiting examples of suitable flavorings include yeast, tallow, processed animal meals (e.g., poultry, beef, lamb, and pork), flavor extracts or blends (e.g., grilled beef), animal digests, and the like. Non-limiting examples of suitable colorings include FD&C colors, such as Blue No. 1, Blue No. 2, Green No. 3, Red No. 3, Red No. 40, Yellow No. 5, Yellow No. 6, and the like; natural colors, such as caramel color, annatto, chlorophyllin, cochineal, betanin, turmeric, saffron, paprika, lycopene, elderberry juice, pandan, butterfly pea, and the like; titanium dioxide; and any suitable food coloring known to the expert in the technique. The pet food compositions described herein may optionally include additional ingredients, such as starches, humectants, oral care ingredients, preservatives, amino acids, fibers, prebiotics, sugars, animal oils, flavorings, other oils in addition to or alternatively to vegetable oils, salts, vitamins, minerals, probiotic microorganisms, bioactive molecules, or combinations thereof. Non-limiting examples of suitable starches include grains such as corn, rice, wheat, barley, oats, potatoes, peas, beans, cassava, and the like, and mixtures of these grains, and may be at least partially included in any flour. Non-limiting examples of suitable humectants include salt, sugars, propylene glycol, and polyhydric glycols such as glycerin and sorbitol, and the like. Non-limiting examples of suitable oral care ingredients include alfalfa nutrient concentrate containing chlorophyll, sodium bicarbonate, phosphates (e.g., tricalcium phosphate, acid pyrophosphates, tetrasodium pyrophosphate, metaphosphates, and orthophosphates), spearmint, cloves, parsley, ginger, and the like. Non-limiting examples of suitable preservatives include potassium sorbate, sorbic acid, sodium methylparaben, calcium propionate, propionic acid, and combinations thereof. The specific amounts of each additional ingredient in the pet food compositions described herein will depend on a variety of factors, such as the ingredient included in the first edible material and any second edible material; the animal species; the animal's age, body weight, general health, sex, and diet; the animal's consumption rate; the purpose for which the food product is administered to the animal; and the like. Therefore, the components and their quantities may vary considerably. Another aspect of the present description is a method for manufacturing a pet food. The method comprises adding MCTs to at least one other edible ingredient. The MCTs are added in an amount effective to provide the health benefits as described herein. For example, the MCTs may be added in such a way that a single serving of the pet food comprises an amount of MCTs effective to treat or prevent sarcopenia or muscle wasting. Example By way of example and not limitation, the following non-limiting study is illustrative of the compositions and methods that use MCTs to control or reduce blood pressure or treat kidney or renal disease in a companion animal, in one or more modalities provided by the present description. Example 1 - Study with aged cats Thirty-two cats were used in this study. The cats ranged in age from 7.6 to 14.4 years at baseline, and there were 13 males and 17 females. The cats were randomly assigned to two groups and fed either the control or test diet to maintain their body weight during the three-month feeding study. QMR was used to determine their lean body mass and body fat at baseline and at the end of the study. Body weight was recorded at baseline and at the end of the study. The diets are shown in Table 1. Table 1 Ingredients Control Test Diet Crude Protein (%) 41.71 40.85 Crude Fat (%) 17.15 21.5 (16% LCT + 5.5% MCT) Moisture (%) 7.82 6.62 Crude Fiber (%) 0.66 0.69 Ash (%) 5.56 6.01 MCT (%) 0 5.5 DHA (%) 0 0.23 EPA (%) 0 0.33 Arginine (%) 1.36 2.25 Vitamin E (mg / kg) 81.00 823.00 Vitamin C (mg / kg) 0 172 The food intake between the two groups is provided in Table 2. Table 2 Average Group (grams) Test 46.25313 Control 49.88644 As shown in Table 2, the average food intake for the control group was higher than for the test group. With a caloric density of 5.05 kcal / g for the control group and 5.33 kcal / g for the test group, the caloric intake for the control group was slightly higher than for the test group (252 kcal for control vs. 247 kcal for test). However, surprisingly, the test group did not lose lean body mass compared to the control group, as shown in Table 3. Also unexpectedly, the test group actually gained body fat compared to the control group (see Table 4) and body weight (see Table 5). Table 3 Baseline Group (mean kg) Treatment (mean kg) Test 3.72 3.72 Controls 4.02 3.81 Table 4 Code PHASE Average % of body fat Baseline Test 26.43 Final Test 29.09 Baseline Control 25.45 Final Control 26.86 Table 5 Diet Change in body weight from baseline (g) Control 0 Test 233 As described above, the results showed that cats fed the test diet gained a higher percentage of body fat than cats fed the control diet (2.66% vs. 1.41%). The test diet increased body fat in adult cats more than a control diet with identical levels of dietary protein and carbohydrate, and a lower level of LCT fat (16% vs. 17.15%). This finding is unexpected, especially since MCTs and omega-3 PUFAs are known for their weight-loss benefits. Furthermore, the results showed that cats fed the test diet gained body weight, while cats fed the control diet did not. This observation contradicts the weight-loss benefits of omega-3 PUFAs and MCTs in other species. It should be understood that several changes and modifications to the preferred embodiments currently described herein will be evident to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present material and without diminishing its anticipated advantages. Therefore, the appended claims are intended to cover such changes and modifications.

Claims

1. A method for treating sarcopenia or muscle atrophy in an animal, the method comprising orally administering to the animal a composition comprising a therapeutically effective amount of medium-chain triglycerides.

2. The method of claim 1, characterized in that the medium-chain triglycerides are approximately 0.5% by weight to approximately 60% by weight of the composition.

3. The method of claim 1, characterized in that the medium-chain triglycerides are approximately 1% by weight to approximately 15% by weight of the composition.

4. The method of claim 1, characterized in that the medium-chain triglycerides include a medium-chain fatty acid selected from the group consisting of caprylic acid, capric acid and a mixture thereof.

5. The method of claim 1, characterized in that the composition further comprises a component selected from the group consisting of an omega-3 fatty acid, antioxidants, arginine, and mixtures thereof.

6. The method of claim 5, characterized in that the omega-3 fatty acid is selected from the group consisting of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and mixtures thereof.

7. The method of claim 1, characterized in that the composition is a complete and nutritionally balanced pet food.

8. The method of claim 1, characterized in that the animal is a pet.

9. The method of claim 1, characterized in that the animal is a cat.

10. The method of claim 1, characterized in that the animal is an adult animal.

11. The method of claim 1, characterized in that the composition is administered to the animal daily for at least one week.

12. The method of claim 1, characterized in that the composition is administered in an amount that provides approximately 0.001 g to approximately 50.0 g of the MCTs per kg of body weight of the animal per day.

13. A method for increasing weight gain, increasing fat gain, or maintaining lean body mass in an animal that needs it, the method comprising orally administering a composition comprising a therapeutically effective amount of medium-chain triglycerides to the animal.

14. The method of claim 13, characterized in that the medium-chain triglycerides are approximately 1% by weight to approximately 15% by weight of the composition.

15. The method of claim 13, characterized in that the composition further comprises a component selected from the group consisting of an omega-3 fatty acid, antioxidants, arginine, and mixtures thereof.

16. The method of claim 13, characterized in that the composition is a complete and nutritionally balanced pet food.

17. The method of claim 13, characterized in that the animal is a pet.

18. The method of claim 13, characterized in that the animal is an adult cat.

19. The method of claim 13, characterized in that the animals requiring it are in post-surgical recovery or suffer from injuries, cancer, AIDS, congestive heart disease, chronic obstructive pulmonary disease, renal failure, severe burns, or cachexia.

20. The method of claim 13, characterized in that the composition is administered in an amount that provides approximately 0.001 g to approximately 50.0 g of the MCTs per kg of the animal's body weight per day.