WO2022225786A1 - Procédés et compositions pour améliorer la force musculaire et/ou réduire la perte musculaire - Google Patents

Procédés et compositions pour améliorer la force musculaire et/ou réduire la perte musculaire Download PDF

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WO2022225786A1
WO2022225786A1 PCT/US2022/024817 US2022024817W WO2022225786A1 WO 2022225786 A1 WO2022225786 A1 WO 2022225786A1 US 2022024817 W US2022024817 W US 2022024817W WO 2022225786 A1 WO2022225786 A1 WO 2022225786A1
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nutritional composition
protein
hmb
hmo
oil
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PCT/US2022/024817
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English (en)
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José María LÓPEZ PEDROSA
Ricardo Rueda Cabrera
Rachael Buck
Suzette Pereira
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Abbott Laboratories
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres

Definitions

  • the present invention relates to methods for improving muscle strength, and/or reducing muscle loss, in a subject, which methods employ at least one human milk oligosaccharide (HMO) selected from the group consisting of an acidic HMO and a neutral HMO, and optionally beta- hydroxy-beta-methylbutyrate (HMB).
  • HMO human milk oligosaccharide
  • the invention also relates to nutritional compositions which employ at least one human milk oligosaccharide (HMO) selected from the group consisting of an acidic HMO and a neutral HMO and HMB, and optionally a plant flavonoid.
  • Sarcopenia is defined as any loss of skeletal muscle mass and strength secondary to aging and/or chronic disease associated with a hypercatabolism state. Sarcopenia includes both muscle loss and muscle dysfunction, which involves contractile impairment and metabolic and endocrine abnormalities. Sarcopenia affects more than 25% of men over 60 years of age and close to 20% of women over 60 years of age, and over half of both men and women over the age of 80.
  • Muscle atrophy complicates many diseases as well as aging, and its presence predicts both decreased quality of life and survival.
  • the main factors that cause muscle atrophy are denervation, musculoskeletal injury, joint immobilization, ligament and joint injury, joint inflammation, prolonged bed rest, sepsis, cancer and aging.
  • Atrophy begins with a reduction in muscle tension, which is reflected in both a decrease in synthesis and an increase in protein degradation.
  • Both autophagic/lysosomal proteolysis and the ubiquitin proteasome system (UPS) are recognized to play important roles in the protein breakdown.
  • therapeutic targeting of the UPS system is more attractive, since inhibition of autophagy leads to dystrophic muscle due to impaired clearance of damaged organelles and aggregated proteins. Oxidative stress has also been well-established as an important inducer of muscle atrophy in both disuse and muscle catabolic cachexia.
  • Glucocorticoids-induced muscle atrophy results from increased protein breakdown and decreased protein synthesis.
  • Increased muscle proteolysis in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of glucocorticoids.
  • the signaling pathway stimulated by glucocorticoids involved a decrease in protein synthesis and an upregulation of atrogenes, in part through a reduction in PI3K/Akt signaling and a concomitant increase in FoxO activity.
  • Treatment with IGF-1 reverted the upregulation. of autophagy-related genes and ubiquitin proteasome elements induced by glucocorticoids.
  • Beta-hydroxy-beta-methylbutyrate has been disclosed as useful in building or maintaining muscle mass and strength in selected individuals.
  • HMB Beta-hydroxy-beta-methylbutyrate
  • the invention is directed to methods for improving muscle strength in a subject, and/or for reducing muscle loss in a subject.
  • One such method comprises administering at least one HMO selected from the group consisting of an acidic HMO and a neutral HMO to the subject, and optionally HMB.
  • Another such method comprises administering HMB, a plant flavonoid, and at least one HMO selected from the group consisting of an acidic HMO and a neutral HMO to the subject.
  • the invention is directed to nutritional compositions.
  • the nutritional composition comprises HMB and at least one HMO selected from the group consisting of an acidic HMO and a neutral HMO.
  • the nutritional composition comprises HMB, a plant flavonoid, and at least one HMO selected from the group consisting of an acidic HMO and a neutral HMO.
  • the methods and nutritional compositions of the invention are advantageous in improving muscle energy production, improving muscle strength, improving muscle contractility, and/or in reducing muscle loss.
  • Fig. 1 shows the results of an evaluation of protein degradation induced by dexamethasone (DEX) as described in the Example;
  • Fig. 2 shows the results of an evaluation of ubiquitin expression induced by dexamethasone (DEX) as described in the Example.
  • the methods and nutritional compositions described herein may comprise, consist of, or consist essentially of the essential steps and elements, respectively, as described herein, as well as any additional or optional steps and elements, respectively, described herein. Any combination of method or process steps as used herein may be performed in any order, unless otherwise specified or clearly implied to the contrary by the context in which the referenced combination is made.
  • the various embodiments of the nutritional compositions of the invention may also be substantially free of any optional or selected ingredient or feature described herein, provided that the remaining nutritional composition still contains all of the required ingredients or features as described herein.
  • the term “substantially free” means that the selected nutritional composition contains less than a functional amount of the optional ingredient, typically less than 1 %, including less than 0.5%, including less than 0.1 %, and also including zero percent, by weight, of such optional or selected essential ingredient.
  • ⁇ MB refers to beta- hydroxy- beta- methylbutyrate (also referred to as beta-hydroxyl-3-methyl butyric acid, beta-hydroxy isovaleric acid) and sources thereof. All weights, percentages, and concentrations as used herein to characterize HMB are based on the weight of HMB, regardless of the source, unless otherwise specified.
  • calcium HMB refers to the calcium salt of beta-hydroxy-beta-methylbutyrate (also referred to as beta-hydroxyl-3-methyl butyric acid, beta-hydroxy isovaleric acid, or HMB), which is most typically in a monohydrate form. All weights, percentages, and concentrations as used herein to characterize calcium HMB are based on the weight of calcium HMB monohydrate, unless otherwise specified.
  • human milk oligosaccharide or “HMO”, as used herein, unless otherwise specified, refers generally to any one or more of a number of complex carbohydrates found in human breast milk that can be acidic or neutral in nature, and to precursors thereof.
  • acidic HMO refers to HMOs that contain sialic acid, i.e., sialylated HMOs.
  • neutral HMO refers to HMOs that lack sialic acid.
  • nutritional composition refers to nutritional liquids and nutritional powders, the latter of which may be reconstituted to form a nutritional liquid, and are suitable for oral consumption by a human.
  • a method for improving muscle strength, and/or reducing muscle loss, in a subject comprises administering at least one HMO selected from the group consisting of an acidic HMO and a neutral HMO to the subject.
  • the method comprises administering HMB and at least one HMO selected from the group consisting of an acidic HMO and a neutral HMO, and optionally a plant flavonoid, to the subject.
  • nutritional compositions are provided.
  • the nutritional composition comprises HMB and at least one HMO selected from the group consisting of an acidic HMO and a neutral HMO.
  • the nutritional composition comprises HMB, a plant flavonoid, and at least one HMO selected from the group consisting of an acidic HMO and a neutral HMO.
  • the inventive nutritional compositions provide a convenient means for conducting the inventive methods.
  • acidic HMOs that may be included individually or in combination in the compositions of the present invention include 3'-sialyl-3-fucosyllactose, disialomonofucosyllacto-N-neohexaose, monofucosylmonosialyllacto-N-octaose (sialyl Lea), sialyllacto-N-fucohexaose II, disialyllacto-N-fucopentaose II, monofucosyldisialyllacto-N-tetraose, 3'-sialyllactose (3’-SL), 3'-sialyllactosamine, 6'-sialyllactose (6’-SL), 6'-sialyllactosamine, sialyllacto-N-neotetraose c, monosi
  • the neutral HMO comprises a fucosylated HMO and/or an N-acetylated HMO.
  • fucosylated and N-acetylated HMOs that may be included individually or in combination in the compositions of the present invention include lacto-N-fucopentaose I, lacto-N-fucopentaose II, 2'-fucosyllactose (2’-FL), 3-fucosyllactose (3- FL), lacto-N-fucopentaose III, lacto-N-difucohexaose I, lactodifucotetraose, lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 2'-fucosyl-N-acetylglucosamine (2'-FLNac), lacto-N- fucopentaose V, lacto
  • the acidic HMO comprises 3’-SL, 6’-SL, or a combination thereof, and/or the at least one neutral HMO comprises 2’-FL, 3-FL, LNT, LNnT, or a combination of two or more thereof.
  • the acidic HMO comprises 6’-SL, and/or the neutral HMO comprises 2’-FL and/or LNT.
  • the methods and nutritional compositions employ at least one acidic HMO and at least one neutral HMO, and, in more specific embodiments, the methods and nutritional compositions employ at least one sialylated HMO, at least one fucosylated HMO, and at least one N-acetylated HMO.
  • a mixture of 3’-SL, 6’-SL, 2’-FL, 3-FL, and LNT is employed,
  • the nutritional compositions of the present invention comprise HMB, which means that the compositions are either formulated with the addition of HMB, most typically as a calcium monohydrate, or are otherwise prepared so as to contain HMB in the finished product.
  • HMB is a naturally occurring amino acid metabolite that is known for use in a variety of nutritional products and supplements.
  • HMB is a metabolite of the essential amino acid leucine and has been shown to modulate protein turnover and inhibit proteolysis.
  • Calcium HMB is a commonly used form of HMB when formulated in oral nutritional products, which products include tablets, capsules, reconstitutable powders, and nutritional liquids and emulsions.
  • HMB is commonly used in nutritional products to help build or maintain healthy muscle in selected individuals
  • HMO selected from the group consisting of an acidic HMO and a neutral HMO
  • any source of HMB is suitable for use in the methods and nutritional compositions of the invention.
  • HMB as the free acid, a salt, including an anhydrous salt, an ester, a lactone, or other product forms that otherwise provide a bioavailable form of HMB.
  • the source of HMB is selected from the group consisting of alkali metal HMB, alkaline earth metal HMB, HMB free acid, HMB lactone and combinations of two or more thereof, or the HMB is selected from the group consisting of sodium HMB, potassium HMB, magnesium HMB, chromium HMB, calcium HMB and combinations of two or more thereof, or the HMB is calcium HMB monohydrate.
  • plant flavonoids are suitable for use in the present methods and nutritional compositions.
  • plant flavonoids which are suitable for use in the methods and nutritional compositions described herein include flavonoids found in fruit, for example, berries, apricots, grapes, citrus fruits, apples, and blueberries, tomatoes, cocoa, chocolate, red wine, tea, celery, mint, parsley, broccoli, kale, leeks, onions, soybeans and the like.
  • Specific plant flavonoids include anthocyanidins, flavanols, flavanones, flavonols, proanthocyanidins, and isoflavones.
  • More specific plant flavonoids which are suitable for use in the nutritional compositions described herein include, but are not limited to, cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, catechins, epicatechins, eriodictyol, hesperidin, hesperetin, naringenin, apigenin, luteolin, isohamnetin, kaempferol, myricetin, quercetin, theaflavins, thearubigins, daidzein, genistein, glycitein, and combinations of two or more thereof.
  • the plant flavonoid comprises citrus flavonoid, or, more specifically, hesperidin, hesperetin, which is the aglycone of hesperidin, narirutin, diosmin, isonaringin, naringin, or didymin, which may be used alone or in combinations of any two or more.
  • the plant flavonoid comprises hesperidin, hesperetin, or a combination thereof. Hesperidin is the major flavonoid present in sweet oranges, but is also found in other citrus fruits including lemon, lime, and mandarin.
  • hesperidin Upon ingestion, hesperidin is hydrolyzed into hesperetin (the aglycone) by colonic microbiota prior to its absorption.
  • hesperetin the aglycone
  • the methods and nutritional compositions as described herein employ an amount of plant flavonoid that is effective to provide additional benefits.
  • the at least one HMO, and optionally the HMB, and optionally, plant flavonoid are administered to the subject orally.
  • the at least one HMO, and optionally HMB, and optionally, the plant flavonoid are administered to the subject in a nutritional composition.
  • the nutritional composition further comprises additional sources of protein, carbohydrate, and/or fat.
  • the nutritional compositions may be liquid nutritional compositions or powdered nutritional compositions.
  • a serving size is about 40 g to about 60 g, or about 45 g to about 50 g, to be administered as a powder or to be reconstituted in about 1 ml to about 500 ml of liquid.
  • a serving ranges about 1 ml to about 500 ml, including about 110 ml to about 500 ml, about 110 ml to about 417 ml, about 120 ml to about 500 ml, about 120 ml to about 417 ml, about 177 ml to about 417 ml, about 207 ml to about 296 ml, about 230 m to about 245 ml, about 110 ml to about 237 ml, about 120 ml to about 245 ml, about 110 ml to about 150 ml, and about 120 ml to about 150 ml.
  • the serving is about 1 ml, or about 100 ml, or about 225 ml, or about 237 ml, or about 500 ml.
  • the at least one HMO and optionally HMB, and optionally, the plant flavonoid are administered to a subject once or multiple times daily or weekly.
  • the at least one HMO and optionally HMB, and optionally, the plant flavonoid are administered to the subject about 1 to about 6 times per day or per week, or about 1 to about 5 times per day or per week, or about 1 to about 4 times per day or per week, or about 1 to about 3 times per day or per week.
  • the at least one HMO and optionally HMB, and optionally, the plant flavonoid are administered once or twice daily for a period of at least one week, at least two weeks, at least three weeks, or at least four weeks.
  • the subject is administered about 0.001 to about 5500 mg, or about 0.01 to about 3000 mg, or about 0.01 to about 300 mg, or about 0.01 to about 75 mg of the at least one HMO per day.
  • the subject is administered about 0.1 to about 10 g, about 0.1 to about 5 g, about 0.5 to about 5 g, 0.5 to about 3 g, or about 0.5 to about 1.5 g of HMB per day.
  • the subject is administered about 50 to about 1000 g, about 50 to about 800 mg, about 50 to about 500 mg, about 100 to about 500 mg, or about 100 to about 300 mg of the plant flavonoid per day.
  • the nutritional composition is in the form of a powder and comprises about 0.0005 to about 5 wt%, or about 0.001 to about 5 wt%, about 0.01 to about 5 wt%, about 0.01 to about 1 wt%, about 0.1 to about 5 wt%, or about 1 to about 5 wt%, of the at least one HMO.
  • the nutritional composition is in the form of a powder and further comprises about 0.005 to about 2.5 wt %, about 0.005 to about 1.5 wt%, about 0.05 to about 1.5 wt%, of HMB; and/or, if the composition comprises a plant flavonoid, about 0.005 to about 0.5 wt %, of the plant flavonoid, all based on the weight of the nutritional composition.
  • the nutritional composition is in the form of a liquid and comprises about 0.0001 to about 0.50 wt%, of the at least one HMO, based on the weight of the nutritional composition.
  • the nutritional composition is in the form of a liquid and further comprises about 0.01 to about 4.5 wt %, about 0.01 to about 2.5 wt%, about 0.1 to about 2.5 wt%, or about 0.1 to about 1.5 wt% of HMB, based on the weight of the nutritional composition; and/or, if the composition comprises a plant flavonoid, about 0.01 to about 0.5 wt %, of the plant flavonoid, based on the weight of the nutritional composition.
  • the nutritional composition further comprises additional sources of protein, carbohydrate, and/or fat, in addition to that provided by the HMO(s) and optionally, HMB and plant flavonoid.
  • the additional source of protein which is contained in the inventive nutritional composition may be any one or more proteins known for use in nutritional compositions. A wide variety of sources and types of protein can be used in the nutritional compositions.
  • the source of protein may include, but is not limited to, intact, hydrolyzed, and partially hydrolyzed protein, which may be derived from any suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, brown rice, corn, barley, etc.), vegetable (e.g., soy, pea, yellow pea, fava bean, chickpea, canola, potato, mung, ancient grains such as quinoa, amaranth, and chia, hemp, flax seed, etc.), and combinations of two or more thereof.
  • milk e.g., casein, whey
  • animal e.g., meat, fish
  • cereal e.g., rice, brown rice, corn, barley, etc.
  • vegetable e.g., soy, pea, yellow pea, fava bean, chickpea, canola, potato, mung, ancient grains such as quinoa, amarant
  • the protein may also include one or a mixture of naturally occurring or synthetic amino acids (often described as free amino acids) and/or their metabolites, known for use in nutritional products, alone or in combination with the intact, hydrolyzed, and/or partially hydrolyzed proteins described herein.
  • the protein in the nutritional composition comprises whole egg powder, egg yolk powder, egg white powder, whey protein, whey protein concentrate, whey protein isolate, whey protein hydrolysate, acid casein, casein protein isolate, sodium caseinate, calcium caseinate, potassium caseinate, casein hydrolysate, milk protein concentrate, milk protein isolate, milk protein hydrolysate, nonfat dry milk, condensed skim milk, whole cow’s milk, partially or completely defatted milk, coconut milk, soy protein concentrate, soy protein isolate, soy protein hydrolysate, pea protein concentrate, pea protein isolate, pea protein hydrolysate, rice protein concentrate, rice protein isolate, rice protein hydrolysate, fava bean protein concentrate, fava bean protein isolate, fava bean protein hydrolysate, collagen protein, collagen protein isolate, meat protein, potato protein, chickpea protein, canola protein, mung protein, quinoa protein, amaranth protein, chia protein,
  • the amount of the source of protein in the nutritional compositions can vary considerably depending upon, for example, the specific dietary needs of the intended user and/or the form of the composition, i.e., liquid or powder.
  • the source of protein in the nutritional composition comprises about 1 wt% to about 30 wt%, about 1 wt% to about 25 wt%, about 1 to about 20 wt%, about 1 to about 15 wt%, about 1 to about 10 wt%, or about 10 wt% to about 30 wt% protein, based on the weight of the nutritional composition.
  • the inventive nutritional compositions may also include an additional source of carbohydrate.
  • the additional source of carbohydrate which is contained in the inventive nutritional composition may be any one or more sources of carbohydrate known for use in nutritional compositions.
  • the carbohydrate comprises maltodextrin, hydrolyzed starch, modified starch, hydrolyzed cornstarch, modified cornstarch, polydextrose, dextrins, corn syrup, corn syrup solids, rice maltodextrin, brown rice mild powder, brown rice syrup, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, maltitol, erythritol, sorbitol, isomaltulose, sucromalt, pullulan, potato starch, corn starch, fructooligosaccharides, galactooligosaccharides, oat fiber, soy fiber, gum arabic, sodium carboxymethylcellulose, methylcellulose, guar gum, gellan gum, locust bean gum, konjac flour, hydroxypropyl
  • the amount of additional source of carbohydrate in the nutritional compositions can vary considerably depending upon, for example, the specific dietary needs of the intended user and/or the form of the composition, i.e. , liquid or powder.
  • the source of carbohydrate in the nutritional composition comprises about 5 wt% to about 75 wt%, about 5 wt% to about 70 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 50 wt%, about 5 wt% to about 40 wt%, about 5 wt% to about 30 wt%, about 5 wt% to about 25 wt%, about 10 wt% to about 65 wt%, about 20 wt% to about 65 wt%, about 30 wt% to about 65 wt%, about 40 wt% to about 65 wt%, or about 15 wt% to about 25 wt% carbohydrate, based on the weight of the nutritional
  • the inventive nutritional compositions may also include an additional source of fat.
  • fat refers to lipids, fats, oils, and combinations thereof.
  • the additional source of fat comprises algal oil, canola oil, flaxseed oil, borage oil, safflower oil, high oleic safflower oil, high gamma-linolenic acid (GLA) safflower oil, corn oil, soy oil, sunflower oil, high oleic sunflower oil, cottonseed oil, coconut oil, fractionated coconut oil, medium chain triglycerides (MCT) oil, palm oil, palm kernel oil, palm olein, long chain polyunsaturated fatty acid, or combinations of two or more thereof.
  • GLA gamma-linolenic acid
  • the amount of an additional source of fat in the nutritional compositions can vary considerably depending upon, for example, the specific dietary needs of the intended user and/or the form of the composition, i.e. , liquid or powder.
  • the nutritional compositions comprise about the nutritional composition comprises from 0.5 wt% to 20 wt%, about 0.5 to about 15 wt%, about 0.5 to about 10 wt%, about 0.5 to about 5 wt%, or about 5 to about 15 wt% fat, based on the weight of the nutritional composition.
  • the relative amounts of the sources of protein, fat and carbohydrate in the nutritional compositions can vary considerably depending upon, for example, the specific dietary needs of the intended user and/or the form of the composition, i.e., liquid or powder.
  • the nutritional composition is administered in the form of a powder and comprises about 10 to about 30 wt% of protein, about 5 to about 15 wt% fat, and about 30 wt% to about 65 wt% carbohydrate, based on the weight of the nutritional composition.
  • the nutritional composition is administered in the form of a liquid and comprises about 1 to about 15 wt% of protein, about 0.5 to about 10 wt% fat, and about 5 to about 30 wt% carbohydrate, based on the weight of the nutritional composition.
  • the nutritional composition comprises at least one protein comprising milk protein concentrate and/or soy protein isolate, at least one fat comprising canola oil, corn oil, coconut oil and/or marine oil, and at least one carbohydrate comprising maltodextrin, sucrose, and/or short-chain fructooligosaccharide.
  • the nutritional composition further comprises one or more nutrients selected from the group consisting of vitamins and minerals.
  • Non-limiting examples of suitable vitamins for use in the methods and nutritional compositions of the invention include vitamin A, vitamin B12, vitamin C, vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, niacin, folic acid, pantothenic acid, biotin, choline, inositol, salts and derivatives thereof, and combinations of two or more thereof.
  • Water soluble vitamins may be added in the form of a water-soluble vitamin (WSV) premix and/or oil-soluble vitamins may be added in one or more oil carriers as desired.
  • suitable minerals for use in the methods and nutritional compositions of the invention include calcium, phosphorus, magnesium, zinc, manganese, sodium, potassium, molybdenum, chromium, chloride, and combinations of two or more thereof.
  • the nutritional composition may also comprise one or more components to modify the physical, chemical, aesthetic, or processing characteristics of the nutritional composition or serve as additional nutritional components.
  • additional components include preservatives, emulsifying agents (e.g., lecithin), buffers, sweeteners including artificial sweeteners (e.g., saccharine, aspartame, acesulfame K, sucralose), colorants, flavorants, thickening agents, stabilizers, and so forth.
  • the nutritional composition has a neutral pH, i.e. , a pH of about 6 to 8 or, more specifically, about 6 to 7.5. In more specific embodiments, the nutritional composition has a pH of about 6.5 to 7.2 or, more specifically, about 6.8 to 7.1.
  • the nutritional compositions may be formed using any techniques known in the art.
  • a powder product can be formed by dry blending ingredients.
  • the nutritional compositions may be formed by preparing an aqueous solution comprising protein and carbohydrate, preparing an oil blend comprising fat and oil-soluble components, and mixing together the aqueous solution and the oil blend to form an emulsified liquid nutritional composition.
  • the HMO(s) and optionally HMB and plant flavonoid may be added at any time as desired in the process, for example, to the aqueous solution or to the emulsified blend.
  • the compositions may be spray-dried or otherwise dried, if a powder product is desired.
  • the nutritional compositions are subjected to a heat treatment which provides sterilization sufficient to maintain microbiological stability of the compositions over a desired shelf-life.
  • This Example demonstrates certain improvements provided by the invention by evaluating the potential effect of HMOs on reducing muscle protein degradation in a well stablished, in-vitro, model of glucocorticoid-induced muscle atrophy.
  • L6.C11 immortalized rat skeletal myoblast cells were grown in Dulbecco’s Modified Eagle’s Medium (DMEM) culture medium supplemented with 10% (v/v) FBS, 2 mmol/l glutamine plus 100 units/ml penicillin and 0.1 mg/ml streptomycin in an atmosphere of 5% CO2 and 95% air and were maintained at sub-confluent densities in the growth media.
  • DMEM Dulbecco’s Modified Eagle’s Medium
  • FBS Modified Eagle’s Medium
  • HMOs 3’-SL, 6’-SL, 2’-FL, 3-FL, and LNT
  • 5HMOs 5HMOs
  • LNT glucocorticoid dexamethasone
  • DEX glucocorticoid dexamethasone
  • the L6.C11 rat skeletal muscle myoblasts were differentiated into myotubes (5 days in differentiation media) and were labeled with 1 pCi/ml of L-[ring-3,5-3H]- Tyrosine for 48 h in DMEM culture medium plus 10% FBS in presence or absence of 5-HMOs.
  • the effects of HMOs on key effectors of muscle atrophy were also studied.
  • the ubiquitin gene is induced to produce the small regulatory ubiquitin protein. Proteins to be degraded are tagged with chains of ubiquitin, a monomeric 76 amino acid protein that becomes the signal that directs the ubiquitinylated protein to the proteasome.
  • the L6.C11 myotubes were pre-incubated for 48 h with increasing amounts of 5-HMOs (0.1-5 g/L) and then incubated for 24 h with 5 mM DEX in the presence or absence of effectors.
  • Figs. 1 and 2 Results are presented in Figs. 1 and 2.
  • incubation of L6.C11 cells with the glucocorticoid dexamethasone induced ubiquitin-gene expression and enhanced protein degradation.
  • Fig. 1 shows that incubation with 0.5 g/L 5-HMOs, alone and in combination with 25 pM HMB, significantly reduced muscle protein degradation induced by the glucocorticoid dexamethasone.
  • * represents p ⁇ 0.05 vs DEX- cells.
  • Fig. 2 shows the effect of increasing doses of 5-HMOs (0.5-5 g/L) were able to decrease the expression of the protein degradation marker ubiquitin.
  • * represents p ⁇ 0.05 vs DEX- cells
  • # represents p ⁇ 0.05 vs Control+DEX cells.

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Abstract

La présente invention concerne un procédé pour améliorer la force musculaire et/ou réduire la perte musculaire chez un patient qui en a besoin, et qui comprend l'administration au patient d'au moins un oligosaccharide du lait maternel (HMO) choisi dans le groupe constitué par un HMO acide et un HMO neutre, et éventuellement du bêta-hydroxy-bêta-méthylbutyrate (HMB) et éventuellement un flavonoïde végétal. Une composition nutritionnelle comprend du HMB et au moins un HMO choisi dans le groupe constitué par un HMO acide et un HMO neutre, et, éventuellement, un flavonoïde végétal.
PCT/US2022/024817 2021-04-22 2022-04-14 Procédés et compositions pour améliorer la force musculaire et/ou réduire la perte musculaire WO2022225786A1 (fr)

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WO2024121153A1 (fr) * 2022-12-05 2024-06-13 Inbiose N.V. Utilisation d'un saccharide sialylé pour maintenir ou améliorer la mobilité chez un patient sain

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WO2010068696A1 (fr) * 2008-12-09 2010-06-17 Metabolic Technologies, Inc. Intervention nutritionnelle permettant d'améliorer la fonctionnalité et la force musculaires
EP2745705A1 (fr) * 2012-12-18 2014-06-25 Abbott Laboratories Usage nutritionnel d'oligosaccharides du lait humain
WO2015077233A1 (fr) * 2013-11-19 2015-05-28 Abbott Laboratories Procédés pour prévenir ou atténuer des réponses allergiques aiguës au moyen d'oligosaccharides de lait humain
WO2015105981A2 (fr) * 2014-01-09 2015-07-16 Abbott Laboratories Essentialité conditionnelle de hmb
WO2016029113A1 (fr) * 2014-08-22 2016-02-25 Abbott Laboratories Procédés d'augmentation de la production endogène de bêta-hydroxy-bêta-méthylbutyrate
EP3494805A1 (fr) * 2017-12-08 2019-06-12 Jennewein Biotechnologie GmbH Tétrasaccharide séché en pulvérisation
WO2019122190A1 (fr) * 2017-12-21 2019-06-27 Societe Des Produits Nestle S.A. Compositions destinées à être utilisées pour favoriser la croissance et le développement des muscles intestinaux et la motilité intestinale associée
CN111165825A (zh) * 2019-07-17 2020-05-19 江苏西宏生物医药有限公司 一种术前经肠营养组合物

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010068696A1 (fr) * 2008-12-09 2010-06-17 Metabolic Technologies, Inc. Intervention nutritionnelle permettant d'améliorer la fonctionnalité et la force musculaires
EP2745705A1 (fr) * 2012-12-18 2014-06-25 Abbott Laboratories Usage nutritionnel d'oligosaccharides du lait humain
WO2015077233A1 (fr) * 2013-11-19 2015-05-28 Abbott Laboratories Procédés pour prévenir ou atténuer des réponses allergiques aiguës au moyen d'oligosaccharides de lait humain
WO2015105981A2 (fr) * 2014-01-09 2015-07-16 Abbott Laboratories Essentialité conditionnelle de hmb
WO2016029113A1 (fr) * 2014-08-22 2016-02-25 Abbott Laboratories Procédés d'augmentation de la production endogène de bêta-hydroxy-bêta-méthylbutyrate
EP3494805A1 (fr) * 2017-12-08 2019-06-12 Jennewein Biotechnologie GmbH Tétrasaccharide séché en pulvérisation
WO2019122190A1 (fr) * 2017-12-21 2019-06-27 Societe Des Produits Nestle S.A. Compositions destinées à être utilisées pour favoriser la croissance et le développement des muscles intestinaux et la motilité intestinale associée
CN111165825A (zh) * 2019-07-17 2020-05-19 江苏西宏生物医药有限公司 一种术前经肠营养组合物

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024121153A1 (fr) * 2022-12-05 2024-06-13 Inbiose N.V. Utilisation d'un saccharide sialylé pour maintenir ou améliorer la mobilité chez un patient sain

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