WO2021067947A1 - Nutritional compositions for the management of hyponatremia - Google Patents
Nutritional compositions for the management of hyponatremia Download PDFInfo
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- WO2021067947A1 WO2021067947A1 PCT/US2020/054283 US2020054283W WO2021067947A1 WO 2021067947 A1 WO2021067947 A1 WO 2021067947A1 US 2020054283 W US2020054283 W US 2020054283W WO 2021067947 A1 WO2021067947 A1 WO 2021067947A1
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- Prior art keywords
- composition
- microns
- hyponatremia
- calcium silicate
- urea
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 59
- 206010021036 Hyponatraemia Diseases 0.000 title claims abstract description 23
- 235000016709 nutrition Nutrition 0.000 title description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000004202 carbamide Substances 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 9
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 29
- 239000000378 calcium silicate Substances 0.000 claims description 29
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 29
- 239000002245 particle Substances 0.000 claims description 28
- 239000000843 powder Substances 0.000 claims description 22
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 229920002774 Maltodextrin Polymers 0.000 claims description 12
- 235000013305 food Nutrition 0.000 claims description 7
- 229920002245 Dextrose equivalent Polymers 0.000 claims description 6
- 239000005913 Maltodextrin Substances 0.000 claims description 6
- 150000004676 glycans Chemical class 0.000 claims description 6
- 229940035034 maltodextrin Drugs 0.000 claims description 6
- 229920001282 polysaccharide Polymers 0.000 claims description 6
- 239000005017 polysaccharide Substances 0.000 claims description 6
- 239000000796 flavoring agent Substances 0.000 claims description 4
- 235000013355 food flavoring agent Nutrition 0.000 claims 3
- 239000004376 Sucralose Substances 0.000 claims 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims 2
- 235000019408 sucralose Nutrition 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000011734 sodium Substances 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 4
- 238000009826 distribution Methods 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 102000002852 Vasopressins Human genes 0.000 description 2
- 108010004977 Vasopressins Proteins 0.000 description 2
- 208000005735 Water intoxication Diseases 0.000 description 2
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229960003726 vasopressin Drugs 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000029422 Hypernatremia Diseases 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 235000019223 lemon-lime Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 229910052914 metal silicate Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 235000021485 packed food Nutrition 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- 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
- 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
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
- A23L29/294—Inorganic additives, e.g. silica
-
- 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
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/718—Starch or degraded starch, e.g. amylose, amylopectin
-
- 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
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides 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
- A61K47/26—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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- 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
- This invention relates to novel urea compositions for oral administration that are useful for treating or managing hyponatremia. Also disclosed are novel methods of making the urea compositions.
- Hyponatremia is an electrolyte abnormality with a potential for significant morbidity and mortality. The condition arises when a person exhibits a positive balance of water with or without a deficit of sodium, which is recognized when the plasma sodium falls below the level of 135 mmol/L. Hyponatremia can occur in isolation in individuals who over-consume water. But more frequently hyponatremia results from a complication of medication or other underlying medical conditions leading to a diminished excretion of water.
- hyponatremia may lead to water intoxication, which results from retention of excess water causing the normal tonicity of extracellular fluid to fall below the safe limit. This may result in a potentially fatal disturbance in brain function.
- Typical symptoms of water intoxication include nausea, vomiting, headache, and malaise. Because nausea may also release anti-diuretic hormone (ADH), which causes water retention, this may cause a positive feedback loop that further worsens the symptoms of hyponatremia. Upon worsening conditions, a patient may experience reduced reflexes, convulsions, stupor, coma, or even death.
- ADH anti-diuretic hormone
- One way of treating hyponatremia is to administer urea to the patient. See, for example, 2014 European Society of Endocrinology, European Society of Intensive Care, European renal Association-EDTA. While the benefits of oral administration of urea are well documented, challenges exist in the development of an oral urea product that is acceptable for patients. Problems include delivering a clinically beneficial amount of urea and the undesirable organoleptic properties of urea compositions. Prior attempts to reduce the bitter taste have included using citric acid.
- One such composition includes urea lOg NaHC03 2 g + citric acid 1.5 g + sucrose 200 mg, which is to be dissolved in 50 to 100 mL water. The resulting solution, however, was found to be not very palatable. Moreover, the composition is severely degraded when exposed to humidity due to reaction of the sodium bicarbonate with the citric acid.
- Ure-NaTM is a powder form of urea.
- This product included 15 g urea doses.
- the composition included urea 15 g, maltodextrin 1.19 g, as well as natural flavor, e.g., cherry or lemon-lime.
- the inventors have found that the original version of Ure-Na suffers from problems including clumping and sticking during packaging. Also, the product was susceptible to caking after periods of storage.
- the inventors have found a need to improve urea compositions to make them easier to manufacture, while maintaining desirable properties for their use in the treatment of hyponatremia.
- the invention relates to a powder composition that can be used to treat hypernatremia.
- the powder composition includes an an amount of urea effective for treatment of hyponatremia; a polysaccharide having a dextrose equivalent (DE) between 3 and 20; and calcium silicate, the calcium silicate having a particle size in the range of 3 to 7 microns, wherein less than 10% of the particles by weight have a diameter less than 3 microns or greater than 7 microns.
- the polysaccharide is preferably maltodextrine.
- the compositions of the invention are useful in delivering urea to patients suffering from hyponatremia, in a form that is useful for oral administration.
- the invention relates to a powder composition that includes (a) 60-80 wt% of urea; (b) 4-15 wt% maltodextrine; and (c) 2-10 wt% calcium silicate, the calcium silicate having a particle size in the range of 3 to 7 microns, wherein less than 10% of the particles by weight have a diameter less than 3 microns or greater than 7 microns.
- the invention in another aspect, relates to methods of treating hyponatremia by orally administering these urea compositions. This may involve dispersing or dissolving the product in water, followed by ingestion.
- the powder may be added to food or a pre-packaged food product.
- the present invention can be broadly described as a more stable powder composition comprising an amount of urea effective for treatment of hyponatremia. It may also involve treating those suffering from hyponatremia, or who are at risk from developing hyponatremia, with the urea composition of the invention.
- the composition may be dispersed in water or another liquid before ingestion by the patient, or may be added to food. Alternatively, the composition may be added to food and packaged until it is ready for use.
- the invention also relates to methods of making urea compositions that avoid manufacturing and packaging problems arising from the active ingredient, urea.
- the inventors have identified several difficulties in the manufacturing of a stable urea composition that arise due to the unique properties of urea, including its hygroscopic nature. For example, the processing of Ure-Na powder has been complicated by sticking of the powder and clumping of the product onto to various parts of the manufacturing and packaging machinery. This required frequent stopping the manufacturing line and cleaning of the processing equipment in order to maintain consistent product quality.
- the present inventors have also found that the Ure-Na product was sometime found to cake during storage, resulting in waste of finished product.
- appropriate selection of calcium silicate is important. Certain versions of calcium silicate having a larger particle sizes with an average particle diameter greater than 7 microns appear to reduce clumping to a lesser degree than particles having a diameter of 5 microns. Accordingly appropriate selection of a metal silicate such a calcium silicate having an average diameter between 3.0 and 7 microns is desired, and more preferably between 4.0 and 6.0 microns. Particles that are larger than these cutoffs take more time to disperse or dissolve in water, whereas particles below these cutoffs contribute to clumping while in the powder state.
- the particle size distribution of the calcium silicate is important such that significant amounts of calcium silicate above the upper limit microns and below the lower limit is undesirable.
- the particle size distribution of the calcium silicate be particularly adapted such that significant amounts below 3.0 microns, and above 7.0 microns, are avoided.
- the calcium silicate have an mean particle diameter within the range of 3.0 and 7.0 microns, and less than 10% of the particles by weight being below 3.0 micron or above 7.0 micron in diameter.
- the calcium silicate has a mean particle diameter within the range of 4.0 and 6.0 microns, desirably a median particle size of 5.0 micron, and less than 10% of the particles by weight being below 4.0 micron and above 6.0 micron in diameter. While the threshold of 10% of particles by weight being outside the target particle diameter range is acceptable. Preferably, even lower amounts of off-target particles is desirable, such as 8%, 6%, 4%, or even 1%. For example, a composition having a mean particle diameter within the range of 4 and 6 microns, with less than 1% by weight outside of that range may be desirable.
- the inventors have found that increased levels of maltodextrine of 9.7% were desirable for decreasing clumping. Therefore, it is desirable to increase the level of maltodextrine to greater than 7% by weight, and more preferably between 7 and 12 wt%, and most preferably 9.7%.
- the invention may be characterized by higher levels of maltodextrine (9.7% versus 6.7%), lower levels of calcium silicate (5% versus 21%), and a controlled particle size distribution for calcium silicate.
- Other embodiments are more broadly characterized by the ranges and amounts disclosed herein.
- the composition preferably has between 60-80 wt%, more preferably 65-75 wt%, and most preferably about 67 wt% urea.
- the composition comprises preferably from 4-15 wt%, more preferably from 7-12 wt%, and most preferably about 9.7 wt% of a polysaccharide having a dextrose equivalent (DE) between 3 and 20.
- DE dextrose equivalent
- the polysaccharide is maltodextrin.
- the composition preferably comprises 2-10 wt%, more preferably 3-8 wt%, and most preferably about 5 wt% calcium silicate.
- the calcium silicate typically includes 99% calcium silicate, and 1% sodium sulfate by weight. The sodium sulfate therefore may be present in the urea powder composition.
- the composition is prepared by adding into a mixer the urea, maltodextrin, and calcium silicate.
- the resulting powder is free flowing a resistant to clumping.
- the powder composition is preferably packaged in a pouch that can be sprinkled onto food, or mixed with a liquid such as water.
- the composition forms a suspension when mixed with water, which allows for convenient ingestion. In this sense, the powder can be distributed and sold as a medical food. Alternatively, the powder may be incorporated into another medical food product such as a cookie or bar form similar to a diet bar.
- Example 1 The product of Example 1 was packaged in pouches using the same packaging used for the previous Ure-NaTM product that lacked calcium silicate. The consumer returns associated with clumping for the previous Ure-NaTM product was 1.4%. Return data for the product of Example 1 was 0.2%.
- the present invention resulted in seven-fold reduction in returns due to clumping relative to existing Ure-NaTM product.
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Abstract
Description
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA3156671A CA3156671A1 (en) | 2019-10-03 | 2020-10-05 | Nutritional compositions for the management of hyponatremia |
JP2022520694A JP2022551848A (en) | 2019-10-03 | 2020-10-05 | Nutritional composition for the management of hyponatremia |
EP20872308.0A EP4037671A4 (en) | 2019-10-03 | 2020-10-05 | Nutritional compositions for the management of hyponatremia |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US201962910142P | 2019-10-03 | 2019-10-03 | |
US62/910,142 | 2019-10-03 |
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WO2021067947A1 true WO2021067947A1 (en) | 2021-04-08 |
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PCT/US2020/054283 WO2021067947A1 (en) | 2019-10-03 | 2020-10-05 | Nutritional compositions for the management of hyponatremia |
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US (2) | US11318092B2 (en) |
EP (1) | EP4037671A4 (en) |
JP (1) | JP2022551848A (en) |
CA (1) | CA3156671A1 (en) |
WO (1) | WO2021067947A1 (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014153044A1 (en) * | 2013-03-14 | 2014-09-25 | Temple University Of The Commonwealth System Of Higher Education | Treatment of patients with hyponatremia and cardiac disease |
US20150142074A1 (en) * | 2008-12-09 | 2015-05-21 | Nephera Ltd. | Stimulation of the urinary system |
US20150351443A1 (en) * | 2014-06-06 | 2015-12-10 | Abbott Laboratories | Hydrating compositions |
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US3914430A (en) * | 1972-04-10 | 1975-10-21 | Hoffmann La Roche | Free-flowing, high density, agglomerated vitamin E powder compositions |
US3947596A (en) * | 1972-04-10 | 1976-03-30 | Hoffmann-La Roche Inc. | Free-flowing, high density, agglomerated vitamin A powder compositions |
KR20100075599A (en) * | 2007-10-03 | 2010-07-02 | 아사히비루 가부시키가이샤 | Granule, tablet, and their production methods |
WO2017151540A1 (en) * | 2016-02-29 | 2017-09-08 | Abbott Laboratories | Nutritional supplement powder |
-
2020
- 2020-10-05 JP JP2022520694A patent/JP2022551848A/en active Pending
- 2020-10-05 WO PCT/US2020/054283 patent/WO2021067947A1/en unknown
- 2020-10-05 US US17/063,327 patent/US11318092B2/en active Active
- 2020-10-05 CA CA3156671A patent/CA3156671A1/en active Pending
- 2020-10-05 EP EP20872308.0A patent/EP4037671A4/en active Pending
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2022
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US20150142074A1 (en) * | 2008-12-09 | 2015-05-21 | Nephera Ltd. | Stimulation of the urinary system |
WO2014153044A1 (en) * | 2013-03-14 | 2014-09-25 | Temple University Of The Commonwealth System Of Higher Education | Treatment of patients with hyponatremia and cardiac disease |
US20150351443A1 (en) * | 2014-06-06 | 2015-12-10 | Abbott Laboratories | Hydrating compositions |
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Title |
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RONDON-BERRIOS ET AL., UREA FOR THE TREATMENT OF HYPONATREMIA, 13 November 2018 (2018-11-13), XP055813739, Retrieved from the Internet <URL:https://cjasn.asnjournals.org/content/clinjasn/13/11/1627.full.pdf?with-ds=yes> [retrieved on 20201207] * |
See also references of EP4037671A4 * |
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EP4037671A4 (en) | 2023-10-11 |
US11318092B2 (en) | 2022-05-03 |
EP4037671A1 (en) | 2022-08-10 |
CA3156671A1 (en) | 2021-04-08 |
US20220226237A1 (en) | 2022-07-21 |
JP2022551848A (en) | 2022-12-14 |
US20210100743A1 (en) | 2021-04-08 |
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