US20220110866A1 - Compositions and methods for improving gastrointestinal absorption of electrolytes - Google Patents
Compositions and methods for improving gastrointestinal absorption of electrolytes Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/42—Phosphorus; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
Definitions
- IECs intestinal epithelial cells
- the intestinal epithelial cells form a selective permeability barrier separating luminal content from underlying tissues.
- the gastrointestinal epithelial lining consists of a monolayer of columnar cells. This monolayer of IECs is constantly moving at a speed of 5-10 ⁇ m/h and is renewed every 2-5 days. The maintenance of this barrier is critical for normal growth, development, and disease prevention. Normally, IECs function as a barrier that prevents undesirable solutes, microorganisms, viruses, and luminal antigens from entering the body.
- junctions function as semi-permeable gates that regulate the passive movement of luminal fluid and solutes through the paracellular pathway, and limit passive diffusion of proteins and lipids between the outer leaflet of the apical and basolateral plasma membrane domains.
- Major transmembrane proteins in the junctions include occludin, claudins, junctional adhesion molecules (JAMs), coxsackie adenovirus receptor (CAR), and E-cadherin.
- the epithelium of the GI track is often damaged by infection and inflammation or upon exposure to toxins. This manifests, frequently, with diarrhea and leads to fluid and electrolyte losses through the GI tract. Thus, it is important to maintain the integrity of the gastrointestinal epithelium, and improving its health and absorptive function once the integrity is compromised after injury.
- the present disclosure in one embodiment, provides compositions and methods for improving gastrointestinal absorption function and correct deficiencies by preserving intestinal epithelial absorptive function.
- the compositions and methods for useful for improving gastrointestinal absorption of electrolytes are provided.
- One embodiment of the disclosure provides a drinkable aqueous solution, comprising about 0.01% to 12% w/v of one or more oligosaccharides, at least 100 mg/L of one or more electrolytes, and water.
- the one or more oligosaccharides include 2′-fucosyllactose (2′-FL), 3′-sialyllactose (3′-SL), 6′-sialyllactose (6′-SL), Lacto-N-tetraose, monofucosyllacto-N-hexaose, Lacto-N-fucopentaose (LNFP) and lacto-N-neotetraose (LNnT).
- LNFP may be selected from the group consisting of LNFP I, LNFP II, LNFP III, LNFP IV and combinations thereof.
- the solution comprises about 0.1% to 5% w/v of the one or more oligosaccharides. In some embodiments, the solution comprises about 0.2% to 2% w/v of the one or more oligosaccharides.
- the one or more oligosaccharides comprise 2′-fucosyllactose (2′-FL), 3′-sialyllactose (3′-SL), or the combination thereof.
- the solution includes less than about 0.5% w/v proteins, or less than about 0.1% w/v proteins. In some embodiments, the solution includes less than about 0.5% w/v lipids, or less than about 0.1% w/v lipids.
- a solid composition obtainable by drying the solution of the present disclosure, or a solid composition suitable for preparing the solution of the present disclosure.
- provided is a method for improving a mammalian subject's absorption of electrolytes comprising administering to the mammalian subject the solution of the present disclosure.
- the subject has gastrointestinal absorption deficiency or suffers from gastrointestinal epithelial injury.
- the instant inventor has made the unexpected discovery that complex oligosaccharides derived from mammalian milk (or from plants and fruits) can improve gastrointestinal absorption of electrolytes and correct deficiencies. Such complex oligosaccharides, it is contemplated, can preserve or improve intestinal epithelial absorptive functions.
- a drinkable aqueous solution that includes one or more oligosaccharides, one or more electrolytes, and water.
- the one or more oligosaccharides are preferably derived from mammalian milk, plant milk, or fruit milk.
- Oligosaccharides are carbohydrates that contain 3 to 10 monosaccharides covalently linked through glycosidic bonds. Human milk contains approximately 7 g of carbohydrates per 100 ml, 90% being lactose, the rest being oligosaccharides. The following principal components (monomers) of oligosaccharides are found in human milk: D-glucose (Glc), D-galactose (Gal), Nacetylglucosamine (GlcNAc), L-fucose (Fuc), N-acetyl neuraminic acid (NeuAc), and N-glycolylneuraminic acid (NeuGc). These components combine in different ways to form 130 different oligosaccharides.
- oligosaccharides found in various types of milk include, without limitation, a-2′-fucosyl-lactose (2′FL), a-3′-galactosyl-lactose (a-3′GL), 3′-galactosyllactose ( ⁇ -3′GL), 6′-galactosyllactose ( ⁇ 6′GL), Fucosyl-Lactosamine, 3′-N-acetylneuraminyllactose (3′-SL), 6′-N-acetylneuraminyllactose (6′-SL), 6′-N-glycolylneuraminyllactose (6′-SL-NGc/NGL), 6′-Sialyl-lactosamine-glycolyl-Neura (6′-SLN/6′-SLacNAc), Diasylyl-Lactose (DSL), N-acetylglucosaminyl-lactose (
- the oligosaccharides include 2′-fucosyllactose (2′-FL), 3′-sialyllactose (3′-SL), 6′-sialyllactose (6′-SL), Lacto-N-tetraose, monofucosyllacto-N-hexaose, lacto-N-neotetraose (LNnT) and various Lacto-N-fucopentaose (LNFP) species, such as LNFP I, LNFP II, LNFP III, and LNFP IV.
- 2′-FL 2′-fucosyllactose
- 3′-SL 3′-sialyllactose
- 6′-SL 6′-sialyllactose
- Lacto-N-tetraose monofucosyllacto-N-hexaose
- lacto-N-neotetraose lacto-
- the solution includes about 0.01% to 12% w/v of the oligosaccharides. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the oligosaccharides.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the oligosaccharides.
- the solution includes about 0.01% to 12% w/v of the 2′-FL. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the 2′-FL.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the 2′-FL.
- the solution includes about 0.01% to 12% w/v of the 3′-SL. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the 3′-SL.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the 3′-SL.
- the solution includes about 0.01% to 12% w/v of the 6′-SL. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the 6′-SL.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the 6′-SL.
- the solution includes about 0.01% to 12% w/v of the Lacto-N-neotetraose. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the Lacto-N-neotetraose.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the Lacto-N-neotetraose.
- the solution includes about 0.01% to 12% w/v of the Lacto-N-tetraose. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the Lacto-N-tetraose.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the Lacto-N-tetraose.
- the solution includes about 0.01% to 12% w/v of the monofucosyllacto-N-hexaose. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the monofucosyllacto-N-hexaose.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the monofucosyllacto-N-hexaose.
- the solution includes about 0.01% to 12% w/v of the LNnT. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the LNnT.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the LNnT.
- the solution includes about 0.01% to 12% w/v of the LNFP. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the LNFP.
- the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the LNFP.
- LNFP species include LNFP I, LNFP II, LNFP III, and LNFP IV.
- the oligosaccharides may be extracted from milk, in some embodiments.
- One or more of the oligosaccharides, in some embodiments, may be obtained from other sources or synthesized, without limitation.
- the oligosaccharides are obtained from milk, in some embodiments, certain other components in the milks are removed. In some embodiments, therefore, the solution does not include certain amount of protein, fiber, or fat.
- the following table lists some major components of various types of milk.
- the solution includes less than about 1% w/v of proteins. In some embodiments, the solution includes less than about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.15%, 0.1%, 0.05%, 0.02%, 0.01%, 0.005%, or 0.001% w/v of proteins.
- the solution includes less than about 1% w/v of fat (or lipids). In some embodiments, the solution includes less than about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.15%, 0.1%, 0.05%, 0.02%, 0.01%, 0.005%, or 0.001% w/v of fat (or lipids).
- the solution includes less than about 1% w/v of cholesterol. In some embodiments, the solution includes less than about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.15%, 0.1%, 0.05%, 0.02%, 0.01%, 0.005%, or 0.001% w/v of cholesterol.
- the solution contains 20 to 400 mg Mg 2+ , or alternatively 30 to 400 mg Mg 2+ , 40 to 400 mg Mg 2+ , 50 to 400 mg Mg 2+ , 50 to 350 mg Mg 2+ , 50 to 300 mg Mg 2+ , 50 to 250 mg Mg 2+ , 50 to 200 mg Mg 2+ , 50 to 150 mg Mg 2+ , 75 to 400 mg Mg 2+ , 75 to 300 mg Mg 2+ , 75 to 250 mg Mg 2+ , 75 to 200 mg Mg 2+ , 75 to 150 mg Mg 2+ , or 75 to 125 mg Mg 2+ , per 16 fluid ounces (473 mL) of the solution.
- the magnesium ion can be provided as a salt of magnesium, such as magnesium citrate, magnesium chloride, without limitation.
- the solution contains 40 to 800 mg/L Mg/L 2+ , or alternatively 60 to 800 mg/L Mg 2+ , 80 to 800 mg/L Mg 2+ , 100 to 800 mg/L Mg 2+ , 100 to 700 mg/L Mg 2+ , 100 to 600 mg/L Mg 2+ , 100 to 500 mg/L Mg 2+ , 100 to 400 mg/L Mg 2+ , 100 to 300 mg/L Mg 2+ , 150 to 800 mg/L Mg 2+ , 150 to 600 mg/L Mg 2+ , 150 to 500 mg/L Mg 2+ , 150 to 400 mg/L Mg 2+ , 150 to 300 mg/L Mg 2+ , or 150 to 250 mg/L Mg 2+ .
- the solution contains about 50 to 800 mg Na + , or alternatively 60 to 700 mg Na + , 70 to 600 mg Na + , 80 to 500 mg Na + , 90 to 400 mg Na + , 100 to 300 mg Na + , 100 to 250 mg Na + , 100 to 225 mg Na + , 100 to 200 mg Na + , 125 to 300 mg Na + , 150 to 300 mg Na + , 175 to 300 mg Na + , 125 to 250 mg Na + , 150 to 250 mg Na + , or 175 to 225 mg Na + , per 16 fluid ounces (473 mL) of the solution.
- the sodium ion can be provided as a salt of sodium, such as sodium citrate, sodium chloride, without limitation.
- the solution contains about 100 to 1600 mg/L Na + , or alternatively 120 to 1400 mg/L Na + , 140 to 1200 mg/L Na + , 160 to 1000 mg/L Na + , 180 to 800 mg/L Na + , 200 to 600 mg/L Na + , 200 to 500 mg/L Na + , 200 to 445 mg/L Na + , 200 to 400 mg/L Na + , 250 to 600 mg/L Na + , 300 to 600 mg/L Na + , 350 to 600 mg/L Na + , 250 to 500 mg/L Na + , 300 to 500 mg/L Na + , or 350 to 445 mg/L Na + .
- the solution contains about 40 to 400 mg K + , or alternatively 50 to 375 mg K + , 60 to 350 mg K + , 70 to 300 mg K + , 80 to 275 mg K + , 90 to 250 mg K + , 100 to 200 mg K + , 110 to 200 mg K + , 120 to 200 mg K + , 130 to 200 mg K + , 140 to 200 mg K + , 150 to 200 mg K + , 100 to 190 mg K + , 100 to 180 mg K + , 100 to 170 mg K + , 100 to 160 mg K + , 110 to 190 mg K + , 120 to 180 mg K + , 130 to 170 mg K + , 140 to 160 mg K + , or 145 to 155 mg K + , per 16 fluid ounces (473 mL) of the solution.
- the potassium ion can be provided as a salt of potassium, such as potassium citrate, potassium chloride, without limitation.
- the solution contains about 80 to 800 mg/L K + , or alternatively 100 to 750 mg/L K + , 120 to 700 mg/L K + , 140 to 600 mg/L K + , 160 to 550 mg/L K + , 180 to 500 mg/L K + , 200 to 400 mg/L K + , 220 to 400 mg/L K + , 240 to 400 mg/L K + , 260 to 400 mg/L K + , 280 to 400 mg/L K + , 300 to 400 mg/L K + , 200 to 380 mg/L K + , 200 to 360 mg/L K + , 200 to 340 mg/L K + , 200 to 320 mg/L K + , 220 to 380 mg/L K + , 240 to 360 mg/L K + , 260 to 340 mg/L K + , 280 to 320 mg/L K + , or 290 to 310 mg/L K + .
- the solution has an osmolarity below 250 mosmoles per liter (mOsm/L). In some embodiments, the osmolarity is below 240 mOsm/L, 230 mOsm/L, 220 mOsm/L, 210 mOsm/L, 200 mOsm/L, 190 mOsm/L, 180 mOsm/L, 170 mOsm/L, 160 mOsm/L, 150 mOsm/L, 140 mOsm/L, 130 mOsm/L, 120 mOsm/L, 110 mOsm/L, 100 mOsm/L, 90 mOsm/L, 80 mOsm/L, 70 mOsm/L, 60 mOsm/L, 50 mOsm/L, 40 mOsm/L, 30 mOsm/L, 20 mOsm/L
- the osmolarity is higher than 1 mOsm/L, 2 mOsm/L, 5 mOsm/L, 10 mOsm/L, 15 mOsm/L, 20 mOsm/L, 30 mOsm/L, 40 mOsm/L, 50 mOsm/L, 70 mOsm/L, 80 mOsm/L, 90 mOsm/L, or 100 mOsm/L.
- the ratio of Mg 2+ to K + is preferably from 1:3 to 2:1, or from 1:2 to 2:1, from 2:3 to 1:1, from 1:3 to 3:2, or from 1:3 to 1:1 (w/w). In some embodiments, the ratio of Mg 2+ to K + is about 1:1, 1:2, 2:3 or 3:4 (w/w).
- the solution can further include other nutrients, amino acids, or flavoring agents such as vitamin C, citric acid, and/or lime/orange flavoring agent.
- Solid compositions are also provided.
- the solid composition once dissolved in water, forms the solution of the present disclosure.
- the solid composition can be obtained by drying the solution of the present disclosure.
- the solutions disclosed herein can be used in methods for improve hydration and correct electrolyte deficiencies. Hydration and electrolyte supplement can help reducing muscle soreness, fatigue or cramping in a subject in need thereof.
- the method in some embodiments, entails orally administering to the subject an effective amount of the solution of the present disclosure.
- the administration follows an intense physical activity by the subject. In one embodiment, the administration is made before an intense physical activity by the subject. In some embodiments, the subject suffers from gastrointestinal absorption deficiency, and/or from gastrointestinal epithelial injury.
- the effective amount is about 1 fluid ounce, 2 fluid ounces, 5 fluid ounces, 10 fluid ounces, 16 fluid ounces, 18 fluid ounces, or 32 fluid ounces, without limitation.
- the subject experiences muscle soreness, fatigue, or cramping. In some embodiments, the subject, following the administration, experiences reduced muscle soreness, fatigue or cramping. In some embodiment, the subject desires the flavor of the solution.
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Abstract
The present disclosure relates generally to compositions and methods for improving gastrointestinal absorption function and correct deficiencies by preserving intestinal epithelial absorptive function. In particular, the compositions and methods for useful for improving gastrointestinal absorption of electrolytes.
Description
- This application is a continuation of U.S. application Ser. No. 16/941,385, filed Jul. 28, 2020, the content of which is incorporated by reference in its entirety into the present disclosure.
- A strong cellular lining is important for a healthy gastrointestinal (GI) track, as it provides a barrier to the billions of microbes and harmful toxins to which the GI tract is exposed. The intestinal epithelial cells (IECs) form a selective permeability barrier separating luminal content from underlying tissues. The gastrointestinal epithelial lining consists of a monolayer of columnar cells. This monolayer of IECs is constantly moving at a speed of 5-10 μm/h and is renewed every 2-5 days. The maintenance of this barrier is critical for normal growth, development, and disease prevention. Normally, IECs function as a barrier that prevents undesirable solutes, microorganisms, viruses, and luminal antigens from entering the body.
- Several elements that participate in the barrier function include the epithelial cells themselves along with tight junctions, adherens junctions, and luminal secretions such as mucus or unstirred layers on the apical aspects of the epithelium. The junctions function as semi-permeable gates that regulate the passive movement of luminal fluid and solutes through the paracellular pathway, and limit passive diffusion of proteins and lipids between the outer leaflet of the apical and basolateral plasma membrane domains. Major transmembrane proteins in the junctions include occludin, claudins, junctional adhesion molecules (JAMs), coxsackie adenovirus receptor (CAR), and E-cadherin.
- The epithelium of the GI track, however, is often damaged by infection and inflammation or upon exposure to toxins. This manifests, frequently, with diarrhea and leads to fluid and electrolyte losses through the GI tract. Thus, it is important to maintain the integrity of the gastrointestinal epithelium, and improving its health and absorptive function once the integrity is compromised after injury.
- The present disclosure, in one embodiment, provides compositions and methods for improving gastrointestinal absorption function and correct deficiencies by preserving intestinal epithelial absorptive function. In particular, the compositions and methods for useful for improving gastrointestinal absorption of electrolytes.
- One embodiment of the disclosure provides a drinkable aqueous solution, comprising about 0.01% to 12% w/v of one or more oligosaccharides, at least 100 mg/L of one or more electrolytes, and water. Non-limiting examples of the one or more oligosaccharides include 2′-fucosyllactose (2′-FL), 3′-sialyllactose (3′-SL), 6′-sialyllactose (6′-SL), Lacto-N-tetraose, monofucosyllacto-N-hexaose, Lacto-N-fucopentaose (LNFP) and lacto-N-neotetraose (LNnT). LNFP may be selected from the group consisting of LNFP I, LNFP II, LNFP III, LNFP IV and combinations thereof.
- In some embodiments, the solution comprises about 0.1% to 5% w/v of the one or more oligosaccharides. In some embodiments, the solution comprises about 0.2% to 2% w/v of the one or more oligosaccharides.
- In some embodiments, the one or more oligosaccharides comprise 2′-fucosyllactose (2′-FL), 3′-sialyllactose (3′-SL), or the combination thereof.
- In some embodiments, the solution includes less than about 0.5% w/v proteins, or less than about 0.1% w/v proteins. In some embodiments, the solution includes less than about 0.5% w/v lipids, or less than about 0.1% w/v lipids.
- Also provided, in some embodiments, is a solid composition obtainable by drying the solution of the present disclosure, or a solid composition suitable for preparing the solution of the present disclosure.
- In some embodiments, provided is a method for improving a mammalian subject's absorption of electrolytes, comprising administering to the mammalian subject the solution of the present disclosure. In some embodiments, the subject has gastrointestinal absorption deficiency or suffers from gastrointestinal epithelial injury.
- The following description sets forth exemplary embodiments of the present technology. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments.
- The instant inventor has made the unexpected discovery that complex oligosaccharides derived from mammalian milk (or from plants and fruits) can improve gastrointestinal absorption of electrolytes and correct deficiencies. Such complex oligosaccharides, it is contemplated, can preserve or improve intestinal epithelial absorptive functions.
- In accordance with one embodiment of the present disclosure, therefore, provided is a drinkable aqueous solution that includes one or more oligosaccharides, one or more electrolytes, and water. The one or more oligosaccharides are preferably derived from mammalian milk, plant milk, or fruit milk.
- Oligosaccharides (OS) are carbohydrates that contain 3 to 10 monosaccharides covalently linked through glycosidic bonds. Human milk contains approximately 7 g of carbohydrates per 100 ml, 90% being lactose, the rest being oligosaccharides. The following principal components (monomers) of oligosaccharides are found in human milk: D-glucose (Glc), D-galactose (Gal), Nacetylglucosamine (GlcNAc), L-fucose (Fuc), N-acetyl neuraminic acid (NeuAc), and N-glycolylneuraminic acid (NeuGc). These components combine in different ways to form 130 different oligosaccharides.
- Examples of oligosaccharides found in various types of milk include, without limitation, a-2′-fucosyl-lactose (2′FL), a-3′-galactosyl-lactose (a-3′GL), 3′-galactosyllactose (β-3′GL), 6′-galactosyllactose (β6′GL), Fucosyl-Lactosamine, 3′-N-acetylneuraminyllactose (3′-SL), 6′-N-acetylneuraminyllactose (6′-SL), 6′-N-glycolylneuraminyllactose (6′-SL-NGc/NGL), 6′-Sialyl-lactosamine-glycolyl-Neura (6′-SLN/6′-SLacNAc), Diasylyl-Lactose (DSL), N-acetylglucosaminyl-lactose (NAL), Glycolyl-neuramyl-lactosamine, N-acetyl-glucosaminyl-hexosyl-lactose (NAHL), N-Di-N-acetyl-glucosaminyl-lactose (DNAL), 3′-Sialyl-6′-galactosyl-lactose (3-SHL), 6′-Sialyl-6′-galactosyl-lactose (6-SHL), N-Glycolyl-neuraminyl-hexosyl-lactose (SNGHL), Sialyl-N-acetylglucosaminyl-lactose, Lacto-N-fuco-pentaose III (LNFPIII), Lacto-N-fuco-pentaose V (LNFPIV), N-Acetyl-glucosaminyl-dihexosyl-lactose (NADHL), N-glycolyl-neuraminyl-lactose (DNGL), Sialyl-di-hexasyl-lactose (SDHL), and Lacto-N-hexaose (LNH). In some embodiments, any of these is suitable for inclusion in the presently disclosed composition.
- In some embodiments, the oligosaccharides include 2′-fucosyllactose (2′-FL), 3′-sialyllactose (3′-SL), 6′-sialyllactose (6′-SL), Lacto-N-tetraose, monofucosyllacto-N-hexaose, lacto-N-neotetraose (LNnT) and various Lacto-N-fucopentaose (LNFP) species, such as LNFP I, LNFP II, LNFP III, and LNFP IV.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the oligosaccharides. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the oligosaccharides. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the oligosaccharides.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the 2′-FL. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the 2′-FL. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the 2′-FL.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the 3′-SL. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the 3′-SL. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the 3′-SL.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the 6′-SL. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the 6′-SL. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the 6′-SL.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the Lacto-N-neotetraose. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the Lacto-N-neotetraose. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the Lacto-N-neotetraose.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the Lacto-N-tetraose. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the Lacto-N-tetraose. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the Lacto-N-tetraose.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the monofucosyllacto-N-hexaose. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the monofucosyllacto-N-hexaose. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the monofucosyllacto-N-hexaose.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the LNnT. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the LNnT. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the LNnT.
- In some embodiments, the solution includes about 0.01% to 12% w/v of the LNFP. In some embodiments, the solution includes at least about 0.001%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10% w/v of the LNFP. In some embodiments, the solution includes no more than about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or 25% w/v of the LNFP. Examples of LNFP species include LNFP I, LNFP II, LNFP III, and LNFP IV.
- The oligosaccharides may be extracted from milk, in some embodiments. One or more of the oligosaccharides, in some embodiments, may be obtained from other sources or synthesized, without limitation.
- When the oligosaccharides are obtained from milk, in some embodiments, certain other components in the milks are removed. In some embodiments, therefore, the solution does not include certain amount of protein, fiber, or fat. The following table lists some major components of various types of milk.
-
TABLE 1 Major components of milk from different sources Nutrient Cow milk Soy milk Almond Oat Human (per 100 ml) (whole) (calcium added) milk milk milk Protein (g) 3.2 2.9 0.64 1.2 1.1 Fat (g) 3.3 1.6 1.2 2.1 4.2 Carbohydrates (g) 4.8 1.7 0.63 6.6 7.5 Calcium (mg) 114 124 212 144 30 Potassium (mg) 133 120 72 160 55 Sodium (mg) 43 37 77 58 15 Cholesterol (mg) 10 0 0 0 14 - In some embodiments, the solution includes less than about 1% w/v of proteins. In some embodiments, the solution includes less than about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.15%, 0.1%, 0.05%, 0.02%, 0.01%, 0.005%, or 0.001% w/v of proteins.
- In some embodiments, the solution includes less than about 1% w/v of fat (or lipids). In some embodiments, the solution includes less than about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.15%, 0.1%, 0.05%, 0.02%, 0.01%, 0.005%, or 0.001% w/v of fat (or lipids).
- In some embodiments, the solution includes less than about 1% w/v of cholesterol. In some embodiments, the solution includes less than about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.15%, 0.1%, 0.05%, 0.02%, 0.01%, 0.005%, or 0.001% w/v of cholesterol.
- As provided, in conditions where the gastrointestinal epithelium is injured, oral electrolyte solutions may not be effectively absorbed. The presently disclosed solution, however, can help a subject absorb the electrolytes. In some embodiments, the solution contains 20 to 400 mg Mg2+, or alternatively 30 to 400 mg Mg2+, 40 to 400 mg Mg2+, 50 to 400 mg Mg2+, 50 to 350 mg Mg2+, 50 to 300 mg Mg2+, 50 to 250 mg Mg2+, 50 to 200 mg Mg2+, 50 to 150 mg Mg2+, 75 to 400 mg Mg2+, 75 to 300 mg Mg2+, 75 to 250 mg Mg2+, 75 to 200 mg Mg2+, 75 to 150 mg Mg2+, or 75 to 125 mg Mg2+, per 16 fluid ounces (473 mL) of the solution. The magnesium ion can be provided as a salt of magnesium, such as magnesium citrate, magnesium chloride, without limitation.
- In some embodiments, the solution contains 40 to 800 mg/L Mg/L2+, or alternatively 60 to 800 mg/L Mg2+, 80 to 800 mg/L Mg2+, 100 to 800 mg/L Mg2+, 100 to 700 mg/L Mg2+, 100 to 600 mg/L Mg2+, 100 to 500 mg/L Mg2+, 100 to 400 mg/L Mg2+, 100 to 300 mg/L Mg2+, 150 to 800 mg/L Mg2+, 150 to 600 mg/L Mg2+, 150 to 500 mg/L Mg2+, 150 to 400 mg/L Mg2+, 150 to 300 mg/L Mg2+, or 150 to 250 mg/L Mg2+.
- In some embodiments, the solution contains about 50 to 800 mg Na+, or alternatively 60 to 700 mg Na+, 70 to 600 mg Na+, 80 to 500 mg Na+, 90 to 400 mg Na+, 100 to 300 mg Na+, 100 to 250 mg Na+, 100 to 225 mg Na+, 100 to 200 mg Na+, 125 to 300 mg Na+, 150 to 300 mg Na+, 175 to 300 mg Na+, 125 to 250 mg Na+, 150 to 250 mg Na+, or 175 to 225 mg Na+, per 16 fluid ounces (473 mL) of the solution. The sodium ion can be provided as a salt of sodium, such as sodium citrate, sodium chloride, without limitation.
- In some embodiments, the solution contains about 100 to 1600 mg/L Na+, or alternatively 120 to 1400 mg/L Na+, 140 to 1200 mg/L Na+, 160 to 1000 mg/L Na+, 180 to 800 mg/L Na+, 200 to 600 mg/L Na+, 200 to 500 mg/L Na+, 200 to 445 mg/L Na+, 200 to 400 mg/L Na+, 250 to 600 mg/L Na+, 300 to 600 mg/L Na+, 350 to 600 mg/L Na+, 250 to 500 mg/L Na+, 300 to 500 mg/L Na+, or 350 to 445 mg/L Na+.
- In some embodiments, the solution contains about 40 to 400 mg K+, or alternatively 50 to 375 mg K+, 60 to 350 mg K+, 70 to 300 mg K+, 80 to 275 mg K+, 90 to 250 mg K+, 100 to 200 mg K+, 110 to 200 mg K+, 120 to 200 mg K+, 130 to 200 mg K+, 140 to 200 mg K+, 150 to 200 mg K+, 100 to 190 mg K+, 100 to 180 mg K+, 100 to 170 mg K+, 100 to 160 mg K+, 110 to 190 mg K+, 120 to 180 mg K+, 130 to 170 mg K+, 140 to 160 mg K+, or 145 to 155 mg K+, per 16 fluid ounces (473 mL) of the solution. The potassium ion can be provided as a salt of potassium, such as potassium citrate, potassium chloride, without limitation.
- In some embodiments, the solution contains about 80 to 800 mg/L K+, or alternatively 100 to 750 mg/L K+, 120 to 700 mg/L K+, 140 to 600 mg/L K+, 160 to 550 mg/L K+, 180 to 500 mg/L K+, 200 to 400 mg/L K+, 220 to 400 mg/L K+, 240 to 400 mg/L K+, 260 to 400 mg/L K+, 280 to 400 mg/L K+, 300 to 400 mg/L K+, 200 to 380 mg/L K+, 200 to 360 mg/L K+, 200 to 340 mg/L K+, 200 to 320 mg/L K+, 220 to 380 mg/L K+, 240 to 360 mg/L K+, 260 to 340 mg/L K+, 280 to 320 mg/L K+, or 290 to 310 mg/L K+.
- In some embodiments, the solution has an osmolarity below 250 mosmoles per liter (mOsm/L). In some embodiments, the osmolarity is below 240 mOsm/L, 230 mOsm/L, 220 mOsm/L, 210 mOsm/L, 200 mOsm/L, 190 mOsm/L, 180 mOsm/L, 170 mOsm/L, 160 mOsm/L, 150 mOsm/L, 140 mOsm/L, 130 mOsm/L, 120 mOsm/L, 110 mOsm/L, 100 mOsm/L, 90 mOsm/L, 80 mOsm/L, 70 mOsm/L, 60 mOsm/L, 50 mOsm/L, 40 mOsm/L, 30 mOsm/L, 20 mOsm/L, 15 mOsm/L, 10 mOsm/L, 9 mOsm/L, 8 mOsm/L, 7 mOsm/L, 6 mOsm/L, 5 mOsm/L, 4 mOsm/L, 3 mOsm/L, 2 mOsm/L, or 1 mOsm/L.
- In some embodiments, the osmolarity is higher than 1 mOsm/L, 2 mOsm/L, 5 mOsm/L, 10 mOsm/L, 15 mOsm/L, 20 mOsm/L, 30 mOsm/L, 40 mOsm/L, 50 mOsm/L, 70 mOsm/L, 80 mOsm/L, 90 mOsm/L, or 100 mOsm/L.
- The ratio of Mg2+ to K+ is preferably from 1:3 to 2:1, or from 1:2 to 2:1, from 2:3 to 1:1, from 1:3 to 3:2, or from 1:3 to 1:1 (w/w). In some embodiments, the ratio of Mg2+ to K+ is about 1:1, 1:2, 2:3 or 3:4 (w/w).
- The solution can further include other nutrients, amino acids, or flavoring agents such as vitamin C, citric acid, and/or lime/orange flavoring agent.
- Solid compositions are also provided. In some embodiments, the solid composition, once dissolved in water, forms the solution of the present disclosure. In some embodiments, the solid composition can be obtained by drying the solution of the present disclosure.
- Specific examples of solutions disclosed here include, without limitation, those provided in Tables 2-4 in the experimental examples.
- In various embodiments, the solutions disclosed herein can be used in methods for improve hydration and correct electrolyte deficiencies. Hydration and electrolyte supplement can help reducing muscle soreness, fatigue or cramping in a subject in need thereof. The method, in some embodiments, entails orally administering to the subject an effective amount of the solution of the present disclosure.
- In some embodiments, the administration follows an intense physical activity by the subject. In one embodiment, the administration is made before an intense physical activity by the subject. In some embodiments, the subject suffers from gastrointestinal absorption deficiency, and/or from gastrointestinal epithelial injury.
- In some embodiments, the effective amount is about 1 fluid ounce, 2 fluid ounces, 5 fluid ounces, 10 fluid ounces, 16 fluid ounces, 18 fluid ounces, or 32 fluid ounces, without limitation.
- In some embodiments, the subject experiences muscle soreness, fatigue, or cramping. In some embodiments, the subject, following the administration, experiences reduced muscle soreness, fatigue or cramping. In some embodiment, the subject desires the flavor of the solution.
- The following examples are included to demonstrate specific embodiments of the disclosure. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques to function well in the practice of the disclosure, and thus can be considered to constitute specific modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure.
- Three test samples of electrolyte drinks were prepared with ingredients shown below.
-
TABLE 2 Sample A Ingredient Amount 2′-fucosyllactose 600 mg (2′-FL) Magnesium 80 mg Potassium 150 mg Sodium 200 mg Vitamin C 100 mg Organic sugar 2000 mg Other ingredients vary (Stevia, monk fruit, citric acid, natural colors) Water 8 fl.oz
Note: Listed are final elemental concentrations of each electrolyte. For instance, 400 mg of sodium chloride contains approximately 200 mg of elemental sodium. -
TABLE 3 Sample B Ingredient Amount 2′-fucosyllactose 600 mg (2′-FL) 3′-sialyllactose 75 mg (3′-SL) Magnesium 80 mg Potassium 150 mg Sodium 200 mg Vitamin C 100 mg Organic sugar 2000 mg Other ingredients vary (Stevia, monk fruit, citric acid, natural colors) Water 8 fl.oz -
TABLE 4 Sample C Ingredient Amount 2′-fucosyllactose 600 mg (2′-FL) 3′-sialyllactose 75 mg (3′-SL) Potassium 150 mg (as chloride and phosphate) Phosphorus 250 mg (as potassium phosphate) Water 8 fl.oz - Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
- The inventions illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms “comprising”, “including,” “containing”, etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed.
- Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification, improvement and variation of the inventions embodied therein herein disclosed may be resorted to by those skilled in the art, and that such modifications, improvements and variations are considered to be within the scope of this invention. The materials, methods, and examples provided here are representative of preferred embodiments, are exemplary, and are not intended as limitations on the scope of the invention.
- The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.
- In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.
- All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entirety, to the same extent as if each were incorporated by reference individually. In case of conflict, the present specification, including definitions, will control.
- It is to be understood that while the disclosure has been described in conjunction with the above embodiments, that the foregoing description and examples are intended to illustrate and not limit the scope of the disclosure. Other aspects, advantages and modifications within the scope of the disclosure will be apparent to those skilled in the art to which the disclosure pertains.
Claims (9)
1. A drinkable aqueous solution comprising from about 0.5 g/L to about 20 g/L of one or more synthesized oligosaccharides selected from the group consisting of 2′-fucosyllactose, 3′-sialyllactose, 6′-sialyllactose, lacto-N-tetraose, monofucosyllacto-N-hexaose, lacto-N-fucopentaose and lacto-N-neotetraose, 150-800 mg/L of magnesium, and water, wherein the aqueous solution does not include more than about 1 g/L of lipids.
2. The drinkable aqueous solution of claim 1 , further comprising 100-1600 mg/L of sodium.
3. The drinkable aqueous solution of claim 2 , further comprising 80-800 mg/L of potassium,
4. The drinkable aqueous solution of claim 3 , further comprising 100-1000 mg/L of phosphorus and 20-800 mg/L of calcium.
5. The drinkable aqueous solution of claim 1 , which does not include more than about 5 g/L of proteins.
6. The drinkable aqueous solution of claim 5 , which does not include more than about 0.1 g/L of lipids.
7. The drinkable aqueous solution of claim 1 , wherein the lacto-N-fucopentaose is selected from the group consisting of lacto-N-fucopentaose I, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose IV and combinations thereof.
8. The drinkable aqueous solution of claim 1 , wherein the one or more synthesized oligosaccharides comprise 2′-fucosyllactose, 3′-sialyllactose, or the combination thereof.
9. A solid composition prepared by drying the drinkable aqueous solution of claim 1 .
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US17/560,192 US20220110866A1 (en) | 2020-07-28 | 2021-12-22 | Compositions and methods for improving gastrointestinal absorption of electrolytes |
US18/469,299 US20240091149A1 (en) | 2020-07-28 | 2023-09-18 | Compositions and methods for improving gastrointestinal absorption of electrolytes |
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US16/941,385 US11285105B2 (en) | 2020-07-28 | 2020-07-28 | Compositions and methods for improving gastrointestinal absorption of electrolytes |
US17/560,192 US20220110866A1 (en) | 2020-07-28 | 2021-12-22 | Compositions and methods for improving gastrointestinal absorption of electrolytes |
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SE427983B (en) | 1980-02-15 | 1983-05-30 | Pripps Bryggerier Ab | BEVERAGE PRODUCTS |
CN100420394C (en) | 2005-08-11 | 2008-09-24 | 黄恒燊 | Sport beverage and preparation method |
EP2455387A1 (en) * | 2010-11-23 | 2012-05-23 | Nestec S.A. | Oligosaccharide mixture and food product comprising this mixture, especially infant formula |
BR112014004772A2 (en) * | 2011-08-29 | 2017-03-21 | Abbott Lab | human milk oligosaccharides to prevent damage and / or promote healing of the gastrointestinal tract |
EP2934190B1 (en) | 2012-12-20 | 2018-12-12 | Abbott Laboratories | Nutritional formulations using human milk oligosaccharides for modulating inflammation |
US10695358B2 (en) * | 2013-12-20 | 2020-06-30 | Abbott Laboratories | Oral rehydration composition with oligosaccharides |
US20180104279A1 (en) * | 2015-04-15 | 2018-04-19 | Prolacta Bioscience, Inc. | Human milk compositions and methods of making and using same |
CN107927788A (en) | 2017-11-09 | 2018-04-20 | 溧阳市迪贝乐生物科技有限公司 | A kind of oligosaccharide nutrient |
CN108308477A (en) | 2018-01-11 | 2018-07-24 | 广东日可威富硒食品有限公司 | A kind of composite rice pulp beverage and preparation method thereof |
US20220054514A1 (en) | 2018-12-20 | 2022-02-24 | Société des Produits Nestlé S.A. | Human milk fortifier composition |
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